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Background: COVID-19 infection is associated with a pro-coagulable state, thrombosis, and cardiovascular events. However, its impact on population-based rates of vascular events is less well understood. We studied temporal trends in hospitalizations for stroke and myocardial infarction in 3 Canadian provinces (Alberta, Ontario, and Nova Scotia) between 2014 and 2022. Methods: Linked administrative data from each province were used to identify admissions for ischemic stroke, intracerebral hemorrhage, cerebral venous thrombosis, and myocardial infarction. Event rates per 100,000/quarter, standardized to the 2016 Canadian population, were calculated. We assessed changes from quarterly rates pre-pandemic (2014-2020), compared to rates in the pandemic period (2020-2022), using interrupted time-series analysis with a jump discontinuity at pandemic onset. Age group– and sex-stratified analyses also were performed. Results: We identified 162,497 strokes and 243,182 myocardial infarctions. At pandemic onset, no significant step change in strokesper 100,000/quarter was observed in any of the 3 provinces. During the pandemic, stroke rates were stable in Alberta and Ontario, but they increased in Nova Scotia (0.44 per 100,000/quarter, P = 0.004). At pandemic onset, a significant step decrease occurred in myocardial infarctions per 100,000/quarter in Alberta (4.72, P < 0.001) and Ontario (4.84, P < 0.001), but not in Nova Scotia. During the pandemic, myocardial infarctions per 100,000/quarter decreased in Alberta (–0.34, P = 0.01), but they remained stable in Ontario and Nova Scotia. No consistent patterns by age group or sex were noted. Conclusions: Hospitalization rates for stroke or myocardial infarction across 3 Canadian provinces did not increase substantially during the first 2 years of the pandemic. Continued surveillance is warranted as the virus becomes endemic. Résumé: Contexte: L’infection par la COVID-19 est associée à un état procoagulant, à la thrombose et à des événements cardiovasculaires. Son incidence sur les taux d'événements vasculaires dans la population est cependant moins bien comprise. Nous avons étudié les tendances temporelles des hospitalisations pour un accident vasculaire cérébral (AVC) et un infarctus du myocarde dans trois provinces canadiennes (Alberta, Ontario et Nouvelle-Écosse) entre 2014 et 2022. Méthodologie: Des données administratives couplées provenant de chaque province ont été utilisées pour recenser les hospitalisations pour un AVC ischémique, une hémorragie intracérébrale, une thrombose veineuse cérébrale et un infarctus du myocarde. Nous avons calculé les taux d’événements pour 100 000 admissions/trimestre, uniformisés pour correspondre à la population canadienne de 2016. Nous avons évalué les variations par rapport aux taux trimestriels d’avant la pandémie (2014-2020), comparativement aux taux pendant la pandémie (2020-2022), à l’aide d’une analyse de séries chronologiques interrompues avec discontinuité à saut fini au début de la pandémie. Des analyses stratifiées selon le groupe d’âge et le sexe ont également été réalisées. Résultats: Nous avons recensé 162 497 AVC et 243 182 infarctus du myocarde. Au début de la pandémie, aucune variation progressive significative au niveau des AVC pour 100 000 admissions/trimestre n’a été observée dans aucune des trois provinces. Pendant la pandémie, les taux d’AVC sont demeurés stables en Alberta et en Ontario, mais ont augmenté en Nouvelle-Écosse (0,44 pour 100 000 admissions/trimestre; p = 0,004). Au début de la pandémie, une diminution graduelle significative du taux d’infarctus du myocarde pour 100 000 admissions/trimestre a été observée en Alberta (4,72; p < 0,001) et en Ontario (4,84; p < 0,001), mais pas en Nouvelle-Écosse. Durant la pandémie, le taux d’infarctus du myocarde pour 100 000 admissions/trimestre a diminué en Alberta (–0,34; p = 0,01), mais est demeuré stable en Ontario et en Nouvelle-Écosse. Aucune tendance constante n’a été observée selon le groupe d’âge ou le sexe. Conclusions: Les taux d’hospitalisation pour un AVC ou un infarctus du myocarde n’ont pas augmenté de manière substantielle dans les trois provinces canadiennes durant les deux premières années de la pandémie. Une surveillance continue s’impose alors que le virus devient endémique.

Abstract Measuring and optimizing a health system is challenging when patient care is split between many independent organizations. For example, patients receive care from their primary care provider, outpatient specialist clinics, hospitals, private providers and, in some instances, family members. These silos are maintained through different funding sources (or lack of funding) which incentivize siloed service delivery. A shift towards prioritizing patient outcomes and keeping the patient at the centre of care is emerging. However, competing philosophies on patient needs, how health is defined and how health is produced and funded is creating and engraining silos in the delivery of health services. Healthcare and health outcomes are produced through a series of activities conducted by diverse teams of health professionals working in concert. Health professionals are continually learning from each patient interaction; however, silos are barriers to information exchange, collaborative evidence generation and health system improvement. This paper presents a systems view of healthcare and provides a systems lens to approach current challenges in health systems. The first part of the paper provides a background on the current state and challenges to healthcare in Canada. The second part presents potential reasons for continued health system underperformance. The paper concludes with a system perspective for addressing these challenges.

Objective Adjusting for stroke severity is critical in stroke outcomes research. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based measure of stroke severity, initially derived in Ontario, Canada using data between 2002-2013. We assessed its geographical and temporal external validity in British Columbia (BC), Nova Scotia (NS), and Ontario, Canada. Methods In each province, we identified adult in-patients with ischemic stroke or intracerebral hemorrhage and admitted from an emergency department between 2014-2019 and calculated their PaSSV score using linked administrative data. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models’ discriminative values using Uno’s c-statistic, comparing models with versus without PaSSV. Results We included 86,142 patients (n=18,387 in BC, n=65,082 in Ontario, n=2,673 in NS). The mean and median PaSSV were similar across provinces. Higher PaSSV score, reflecting lower stroke severity, was associated with a lower mortality (hazard ratio and 95% confidence intervals 0.70 [0.68-0.71] in BC, 0.69 [0.68-0.69] in Ontario, 0.72 [0.68-0.75] in NS) and long-term care admission (0.77 [0.76-0.79] in BC, 0.84 [0.83-0.85] in Ontario, 0.86 [0.79-0.93] in NS). Including PaSSV in the multivariable models improved model fit according to the c-statistics. Conclusion We showed that PaSSV has geographical and temporal validity. It is a useful tool for risk-adjustment in multi-jurisdiction stroke outcomes research, and a valuable addition to be included in the national algorithm inventory.

Background and Purpose Infarcts in acute ischemic stroke (AIS) patients may continue to grow even after reperfusion, due to mechanisms such as microvascular obstruction and reperfusion injury. We investigated whether and how much infarcts grow in AIS patients after near-complete (expanded Thrombolysis in Cerebral Infarction [eTICI] 2c/3) reperfusion following endovascular treatment (EVT), and to assess the association of post-reperfusion infarct growth with clinical outcomes. Methods Data are from a single-center retrospective observational cohort study that included AIS patients undergoing EVT with near-complete reperfusion who received diffusion-weighted magnetic resonance imaging (MRI) within 2 hours post-EVT and 24 hours after EVT. Association of infarct growth between 2 and 24 hours post-EVT and 24-hour National Institutes of Health Stroke Scale (NIHSS) as well as 90-day modified Rankin Scale score was assessed using multivariable logistic regression. Results Ninety-four of 155 (60.6%) patients achieved eTICI 2c/3 and were included in the analysis. Eighty of these 94 (85.1%) patients showed infarct growth between 2 and 24 hours post-reperfusion. Infarct growth ≥5 mL was seen in 39/94 (41.5%) patients, and infarct growth ≥10 mL was seen in 20/94 (21.3%) patients. Median infarct growth between 2 and 24 hours post-reperfusion was 4.5 mL (interquartile range: 0.4–9.2 mL). Post-reperfusion infarct growth was associated with the 24-hour NIHSS in multivariable analysis (odds ratio: 1.16 [95% confidence interval 1.09–1.24], P

Abstract Background Health research partnership approaches have grown in popularity over the past decade, but the systematic evaluation of their outcomes and impacts has not kept equal pace. Identifying partnership assessment tools and key partnership characteristics is needed to advance partnerships, partnership measurement, and the assessment of their outcomes and impacts through systematic study. Objective To locate and identify globally available tools for assessing the outcomes and impacts of health research partnerships. Methods We searched four electronic databases (Ovid MEDLINE, Embase, CINAHL + , PsychINFO) with an a priori strategy from inception to June 2021, without limits. We screened studies independently and in duplicate, keeping only those involving a health research partnership and the development, use and/or assessment of tools to evaluate partnership outcomes and impacts. Reviewer disagreements were resolved by consensus. Study, tool and partnership characteristics, and emerging research questions, gaps and key recommendations were synthesized using descriptive statistics and thematic analysis. Results We screened 36 027 de-duplicated citations, reviewed 2784 papers in full text, and kept 166 studies and three companion reports. Most studies originated in North America and were published in English after 2015. Most of the 205 tools we identified were questionnaires and surveys targeting researchers, patients and public/community members. While tools were comprehensive and usable, most were designed for single use and lacked validity or reliability evidence. Challenges associated with the interchange and definition of terms (i.e., outcomes, impacts, tool type) were common and may obscure partnership measurement and comparison. Very few of the tools identified in this study overlapped with tools identified by other, similar reviews. Partnership tool development, refinement and evaluation, including tool measurement and optimization, are key areas for future tools-related research. Conclusion This large scoping review identified numerous, single-use tools that require further development and testing to improve their psychometric and scientific qualities. The review also confirmed that the health partnership research domain and its measurement tools are still nascent and actively evolving. Dedicated efforts and resources are required to better understand health research partnerships, partnership optimization and partnership measurement and evaluation using valid, reliable and practical tools that meet partners’ needs.

Background Risk of recurrence after minor ischemic stroke is usually reported with transient ischemic attack. No previous meta‐analysis has focused on minor ischemic stroke alone. The objective was to evaluate the pooled proportion of 90‐day stroke recurrence for minor ischemic stroke, defined as a National Institutes of Health Stroke Scale severity score of ≤5. Methods and Results Published papers found on PubMed from 2000 to January 12, 2021, reference lists of relevant articles, and experts in the field were involved in identifying relevant studies. Randomized controlled trials and observational studies describing minor stroke cohort with reported 90‐day stroke recurrence were selected by 2 independent reviewers. Altogether 14 of 432 (3.2%) studies met inclusion criteria. Multilevel random‐effects meta‐analysis was performed. A total of 6 randomized controlled trials and 8 observational studies totaling 45 462 patients were included. The pooled 90‐day stroke recurrence was 8.6% (95% CI, 6.5–10.7), reducing by 0.60% (95% CI, 0.09–1.1; P=0.02) with each subsequent year of publication. Recurrence was lowest in dual antiplatelet trial arms (6.3%, 95% CI, 4.5–8.0) when compared with non‐dual antiplatelet trial arms (7.2%, 95% CI, 4.7–9.6) and observational studies 10.6% (95% CI, 7.0–14.2). Age, hypertension, diabetes, ischemic heart disease, or known atrial fibrillation had no significant association with outcome. Defining minor stroke with a lower National Institutes of Health Stroke Scale threshold made no difference – score ≤3: 8.6% (95% CI, 6.0–11.1), score ≤4: 8.4% (95% CI, 6.1–10.6), as did excluding studies with n

Background In the wake of pandemic‐related health decline and health care disruptions, there are concerns that previous gains for cardiovascular risk factors may have stalled or reversed. Population‐level excess burden of drug‐treated diabetes and hypertension during the pandemic compared with baseline is not well characterized. We evaluated the change in incident prescription claims for antihyperglycemics and antihypertensives before versus during the pandemic. Methods and Results In this retrospective, serial, cross‐sectional, population‐based study, we used interrupted time series analyses to examine changes in the age‐ and sex‐standardized monthly rate of incident prescriptions for antihyperglycemics and antihypertensives in patients aged ≥66 years in Ontario, Canada, before the pandemic (April 2014 to March 2020) compared with during the pandemic (July 2020 to November 2022). Incident claim was defined as the first prescription filled for any medication in these classes. The characteristics of patients with incident prescriptions of antihyperglycemics (n=151 888) or antihypertensives (n=368 123) before the pandemic were comparable with their pandemic counterparts (antihyperglycemics, n=97 015; antihypertensives, n=146 524). Before the pandemic, monthly rates of incident prescriptions were decreasing (−0.03 per 10 000 individuals [95% CI, −0.04 to −0.01] for antihyperglycemics; −0.14 [95% CI, −0.18 to −0.10] for antihypertensives). After July 2020, monthly rates increased (postinterruption trend 0.31 per 10 000 individuals [95% CI, 0.28–0.34] for antihyperglycemics; 0.19 [95% CI, 0.14–0.23] for antihypertensives). Conclusions Population‐level increases in new antihyperglycemic and antihypertensive prescriptions during the pandemic reversed prepandemic declines and were sustained for >2 years. Our findings are concerning for current and future cardiovascular health.

Background Nerinetide treatment was associated with better clinical outcomes among patients with stroke undergoing endovascular treatment who were not treated with concurrent alteplase in the randomized ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial. In patients receiving alteplase, no such effect was seen due to an inactivation of nerinetide by plasmin – the product of tissue plasminogen activation. We hypothesized that improved outcomes in the no‐alteplase patients were associated with reduced infarct growth, a radiological correlate of improved stroke outcomes. Methods Data are from the no‐alteplase stratum of the ESCAPE‐NA1 trial. Patients who underwent computer tomography perfusion (CTP) as part of routine clinical care were included. Admission CTP source data were processed using RAPID software. Infarct core at baseline was defined as areas of relative cerebral blood flow

Abstract Although a decrease in stroke admissions during the SARS-CoV-2 pandemic has been observed, detailed analyses of the evolution of stroke metrics during the pandemic are lacking. We analyzed changes in stroke presentation, in-hospital systems-of-care, and treatment time metrics at two representative Comprehensive Stroke Centers (CSCs) during the first year of Coronavirus disease 2019 pandemic. From January 2018 to May 2021, data from stroke presentations to two CSCs were obtained. The study duration was split into: period 0 (prepandemic), period 1 (Wave 1), period 2 (Lull), and period 3 (Wave 2). Acute stroke therapies rates and workflow times were compared among pandemic and prepandemic periods. Analyses were adjusted for age, sex, comorbidities, and pre-morbid care needs. There was a significant decrease in monthly hospital presentations of stroke during Wave 1. Both centers reported declines in reperfusion therapies during Wave 1, slowly catching up but never to pre pandemic numbers, and dropping again in Wave 2. Both CSCs experienced in-hospital workflow delays during Waves 1 and 2, and even during the Lull period. Our results highlight the need for proactive strategies to reduce barriers to workflow and hospital avoidance for stroke patients during crisis periods.

Abstract Background Patients with ischemic stroke and atrial fibrillation (AF) are at particularly high risk for recurrent stroke and cardiovascular events. Early rhythm control has been shown to be superior to usual care for the prevention of stroke and cardiovascular events for people with early AF. There are no data on the willingness to use rhythm control for patients with AF and acute ischemic stroke in clinical practice. Methods An online survey was carried out among stroke physicians to assess current practice and attitudes toward rhythm control in patients with AF and acute ischemic stroke between December 22nd 2021 and March 24th 2022. Results The survey was completed by 277 physicians including 237 from 15 known countries and 40 from unspecified countries. 79% (210/266) reported that they do not regularly apply treatment for rhythm control by ablation or antiarrhythmic drugs at all or only in small numbers (≤ 10%) of patients with AF and acute ischemic stroke. In those patients treated with rhythm-control therapy, antiarrhythmic drugs were used by the majority of respondents (89%), while only a minority reported using AF ablation (11%). 88% of respondents (221/250) stated that they would be willing to randomize patients with AF after acute ischemic stroke to either early rhythm control or usual care in a clinical trial. Conclusion Despite its potential benefit, few patients with AF and acute ischemic stroke appear to be treated with rhythm control, which may result from uncertainty regarding potential complications of antiarrhythmic therapy in patients with acute stroke. Together with recent data on the effectiveness of early rhythm control in patients with a history of stroke, these results call for a randomized clinical trial to assess the efficacy of early rhythm control in patients with acute ischemic stroke and AF.

Background and aimRapid outpatient evaluation and treatment of TIA in structured clinics have been shown to reduce stroke recurrence. It is unclear whether short-term downtrends in TIA incidence and admissions have had enduring impact on TIA clinic activity. This study aims to measure the impact of the pandemic on hospitals with rapid TIA clinics.MethodsRelevant services were identified by literature search and contacted. Three years of monthly data were requested – a baseline pre-COVID period (April 2018 to March 2020) and an intra-COVID period (April 2020 to March 2021). TIA presentations, ischemic stroke presentations, and reperfusion trends inclusive of IV thrombolysis (IVT) and endovascular thrombectomy (EVT) were recorded. Pandemic impact was measured with interrupted time series analysis, a segmented regression approach to test an effect of an intervention on a time-dependent outcome using a defined impact model.ResultsSix centers provided data for a total of 6,231 TIA and 13,191 ischemic stroke presentations from Australia (52.1%), Canada (35.0%), Italy (7.6%), and England (5.4%). TIA clinic volumes remained constant during the pandemic (2.9, 95% CI –1.8 to 7.6, p = 0.24), as did ischemic stroke (2.9, 95% CI –7.8 to 1.9, p = 0.25), IVT (−14.3, 95% CI −36.7, 6.1, p

This prospective, community-based, active surveillance study aimed to report the incidence of moderate, severe, and serious adverse events (AEs) after chiropractic (n = 100) / physiotherapist (n = 50) visit in offices throughout North America between October-2015 and December-2017. Three content-validated questionnaires were used to collect AE information: two completed by the patient (pre-treatment [T0] and 2-7 days post-treatment [T2]) and one completed by the provider immediately post-treatment [T1]. Any new or worsened symptom was considered an AE and further classified as mild, moderate, severe or serious. From the 42 participating providers (31 chiropractors; 11 physiotherapists), 3819 patient visits had complete T0 and T1 assessments. The patients were on average 50±18 years of age and 62.5% females. Neck/back pain was the most common presenting condition (70.0%) with 24.3% of patients reporting no condition/preventative care. From the patients visits with a complete T2 assessment (n = 2136 patient visits, 55.9%), 21.3% reported an AE, of which: 7.9% were mild, 6.2% moderate, 3.7% severe, 1.5% serious, and 2.0% had missing severity rating. The most common symptoms reported with moderate or higher severity were discomfort/pain, stiffness, difficulty walking and headache. This study provides valuable information for patients and providers regarding incidence and severity of AEs following patient visits in multiple community-based professions. These findings can be used to inform patients of what AEs may occur and future research opportunities can focus on mitigating common AEs.

Abstract Background Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. Methods The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. Discussion OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of “damage control”; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. Trial registration: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Abstract Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID‐19). Conventional meta‐analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID‐19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID‐19. We evaluated the overall treatment group effect by log‐likelihood ratio test (−2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (−2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614–1.610; −2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta‐analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome‐coronavirus 2 viral clearance and COVID‐19 hospitalization did not show a clinical benefit of HCQ. Our meta‐analysis provides evidence to support the interruption in the use of HCQ in mild COVID‐19 outpatients to reduce progression to severe disease.

Background The optimal management of patients with symptomatic isolated internal carotid artery (ICA) occlusion is unknown. We aimed to assess whether endovascular treatment (EVT) compared with standard medical care was associated with improved functional outcomes in patients with acute symptomatic isolated intracranial ICA occlusion without involvement of the middle or anterior cerebral artery, that is, ICA‐I occlusion. Additionally, we aimed to compare ICA‐I with ICA‐L/T occlusion, which involves themiddle and anterior cerebral artery, respectively. Methods We analyzed data from the highly effective reperfusion evaluated in multiple endovascular stroke trials (HERMES) collaboration, which performed an individual patient data meta‐analysis of 7 randomized controlled trials conducted between 2010 and 2017 assessing the benefit of EVT compared to medical management in patients with anterior circulation large vessel occlusion. We assessed the association between EVT and 90‐day good functional outcome (modified Rankin scale scores 0–2), National Institutes of Health Stroke Scale scores at 24 hours, symptomatic intracranial hemorrhage rates and mortality in patients with ICA‐I and ICA‐L/T occlusion. Results We included 442 patients with intracranial ICA occlusion, of whom 38 (8.6%) had ICA‐I occlusion. In the ICA‐I group, the median age [interquartile range] was 69.5 [61.7–79.5] years, 42.1% were male, and median baseline National Institutes of Health Stroke Scale was 17 [15–20]. Compared with standard medical care alone, EVT resulted in higher good outcome rates in patients with ICA‐I (42.9% versus 25%; P=0.296) and ICA‐L/T occlusion (32.5% versus 14.4%; P

BackgroundHigh blood pressure (BP) is the primary risk factor for recurrent strokes. Despite established clinical guidelines, some stroke survivors exhibit uncontrolled BP over the first 12 months post-stroke. Furthermore, research on BP trajectories in stroke survivors admitted to inpatient rehabilitation hospitals is limited. Exercise is recommended to reduce BP after stroke. However, the effect of high repetition gait training at aerobic intensities (>40% heart rate reserve; HRR) during inpatient rehabilitation on BP is unclear. We aimed to determine the effect of an aerobic gait training intervention on BP trajectory over the first 12 months post-stroke.MethodsThis is a secondary analysis of the Determining Optimal Post-Stroke Exercise (DOSE) trial. Participants with stroke admitted to inpatient rehabilitation hospitals were recruited and randomized to usual care (n = 24), DOSE1 (n = 25; >2,000 steps, 40–60% HRR for >30 min/session, 20 sessions over 4 weeks), or DOSE2 (n = 25; additional DOSE1 session/day) groups. Resting BP [systolic (SBP) and diastolic (DBP)] was measured at baseline (inpatient rehabilitation admission), post-intervention (near inpatient discharge), 6- and 12-month post-stroke. Linear mixed-effects models were used to examine the effects of group and time (weeks post-stroke) on SBP, DBP and hypertension (≥140/90 mmHg; ≥130/80 mmHg, if diabetic), controlling for age, stroke type, and baseline history of hypertension.ResultsNo effect of intervention group on SBP, DBP, or hypertension was observed. BP increased from baseline to 12-month post-stroke for SBP (from [mean ± standard deviation] 121.8 ± 15.0 to 131.8 ± 17.8 mmHg) and for DBP (74.4 ± 9.8 to 78.5 ± 10.1 mmHg). The proportion of hypertensive participants increased from 20.8% (n = 15/72) to 32.8% (n = 19/58). These increases in BP were statistically significant: an effect [estimation (95%CI), value of p] of time was observed on SBP [0.19 (0.12–0.26) mmHg/week, p

Abstract Background Accurate, consistent assessment of outcomes and impacts is challenging in the health research partnerships domain. Increased focus on tool quality, including conceptual, psychometric and pragmatic characteristics, could improve the quantification, measurement and reporting partnership outcomes and impacts. This cascading review was undertaken as part of a coordinated, multicentre effort to identify, synthesize and assess a vast body of health research partnership literature. Objective To systematically assess the outcomes and impacts of health research partnerships, relevant terminology and the type/use of theories, models and frameworks (TMF) arising from studies using partnership assessment tools with known conceptual, psychometric and pragmatic characteristics. Methods Four electronic databases were searched (MEDLINE, Embase, CINAHL Plus and PsycINFO) from inception to 2 June 2021. We retained studies containing partnership evaluation tools with (1) conceptual foundations (reference to TMF), (2) empirical, quantitative psychometric evidence (evidence of validity and reliability, at minimum) and (3) one or more pragmatic characteristics. Outcomes, impacts, terminology, definitions and TMF type/use were abstracted verbatim from eligible studies using a hybrid (independent abstraction–validation) approach and synthesized using summary statistics (quantitative), inductive thematic analysis and deductive categories (qualitative). Methodological quality was assessed using the Quality Assessment Tool for Studies with Diverse Designs (QATSDD). Results Application of inclusion criteria yielded 37 eligible studies. Study quality scores were high (mean 80%, standard deviation 0.11%) but revealed needed improvements (i.e. methodological, reporting, user involvement in research design). Only 14 (38%) studies reported 48 partnership outcomes and 55 impacts; most were positive effects (43, 90% and 47, 89%, respectively). Most outcomes were positive personal, functional, structural and contextual effects; most impacts were personal, functional and contextual in nature. Most terms described outcomes (39, 89%), and 30 of 44 outcomes/impacts terms were unique, but few were explicitly defined (9, 20%). Terms were complex and mixed on one or more dimensions (e.g. type, temporality, stage, perspective). Most studies made explicit use of study-related TMF (34, 92%). There were 138 unique TMF sources, and these informed tool construct type/choice and hypothesis testing in almost all cases (36, 97%). Conclusion This study synthesized partnership outcomes and impacts, deconstructed term complexities and evolved our understanding of TMF use in tool development, testing and refinement studies. Renewed attention to basic concepts is necessary to advance partnership measurement and research innovation in the field. Systematic review protocol registration: PROSPERO protocol registration: CRD42021137932 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=137932 .

Background The benefit of endovascular thrombectomy for medium‐vessel occlusion (MeVO) strokes is unclear. We used 90‐day home time to explore outcomes in patients with MeVO versus large‐vessel occlusions treated with endovascular thrombectomy. Methods Data are from the QuICR (Quality Improvement and Clinical Research) provincial stroke registry and linked administrative data to identify patients who underwent endovascular thrombectomy in our center from January 2015 to December 2020. Imaging data were scored by 2‐physician consensus. We defined MeVO as occlusion beyond and including M2–middle cerebral artery, A2–anterior cerebral artery, or P2–posterior cerebral artery segments. Successful reperfusion was defined as Thrombolysis in Cerebral ischemia grades (≥2b/3). The primary outcome was patient home time (the number of nights a patient is back at their premorbid living situation without an increase in level of care within 90 days of the stroke) using random forest regression. Covariate contribution to home time was determined using partial dependence plots. Results Among 663 patients who underwent endovascular thrombectomy, 139 (20.9%) had MeVO (median age, 71 years; 50.4% women; median National Institutes of Health Stroke Scale, 16). The majority (82%) had good pial collaterals, 10.4% had a tandem extracranial carotid occlusion or stenosis, and 41.7% received intravenous thrombolysis. The most common site of occlusion was M2–middle cerebral artery (58.3%). One hundred eighteen (86.7%) patients achieved successful reperfusion (Thrombolysis in Cerebral Ischemia grades ≥2b/3). Using partial dependence plots, the mean predicted home times were similar in patients with MeVO (45.5 days) versus large‐vessel occlusions (44.6 days). Factors predicting lower 90‐day home time in patients with MeVOs were diabetes (−8.7 days), hypertension (−6.5 days), and atrial fibrillation (−3.5 days). There was no meaningful difference in predicted 90‐day home‐time by sex, baseline National Institutes of Health Stroke Scale, collateral grade, or thrombolysis. Conclusion Patients with MeVO who are selected for endovascular therapy with similar demographic and clinical profiles to large‐vessel occlusions can achieve similar 90‐day home time outcomes to large‐vessel occlusions.

Cognitive deficits are common poststroke. Cognitive rehabilitation is typically used to improve cognitive deficits. It is unknown whether higher doses of exercise to promote motor recovery influence cognitive outcomes. Our recent trial, Determining Optimal Post-Stroke Exercise (DOSE), shows more than double the steps and aerobic minutes can be achieved during inpatient rehabilitation versus usual care, and translates to improved long-term walking outcomes. Thus, the secondary analysis aim was to determine the effect of the DOSE protocol on cognitive outcomes over 1-year poststroke. The DOSE protocol progressively increased step number and aerobic minutes during inpatient stroke rehabilitation over 20 sessions. The Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Trail Making Test B were completed at baseline, post-intervention, and 6- and 12-months poststroke, administered using standardized guidelines. Using the DOSE data, we used mixed-effect spline regression to model participants’ trajectories of cognitive recovery, controlling for relevant covariates. Participants (Usual Care n = 25, DOSE n = 50) were 56.7(11.7) years old, and 27(10) days post stroke. For the MoCA, there were statistically significant Group × Trajectory(p = 0.019), and Group × ΔTrajectory (p = 0.018) interactions with a substantial clinically meaningful difference, from +5.44 points/month improvement of the DOSE group compared to +1.59 points/month improvement with Usual Care during the 4-week intervention. The DSST and Trails B improved over time but were not different between groups. Taking advantage of this early difference may lend support to continued efforts to increase intensity, during and after discharge from inpatient rehabilitation, to improve cognition.Clinical trial registration: www.clinicaltrials.gov, NCT01915368.

Objectives We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.Design Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.Setting 352 community family practices across 4 Canadian provinces between March 2017 and September 2020.Participants 552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.Intervention Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.Primary and secondary outcome measures Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.Results At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p

Abstract The long-term impact of COVID-19 among those with mild infections is not well characterized. Among 81 adults who completed online assessments at 3- and 12-months following infection, quality of life scores did not significantly improve over time. Among 62 subjects who also completed telephone interviews, respiratory symptoms or exercise limitation were reported by 42% at a median follow-up of 387 days (IQR 251–402 days). Those with persistent respiratory symptoms scored lower on the EQ-5D visual analog score compared to those without. Persistent respiratory symptoms were associated with a lower likelihood of full-time employment at 1 year (aOR 0.09, 95%CI 0.01–0.91; P = 0.041). In an adjusted linear regression, persistent respiratory symptoms (P = 0.037) and female sex (P = 0.016) were both independent risks for increased visits to a primary care provider. This cohort study demonstrates that respiratory symptoms are frequent at 1 year following COVID-19 and more importantly, are associated with negative impacts on employment, quality of life, and health care utilization. Further research is needed to determine the pathophysiology and risk factors for persistent symptoms as well as optimal management strategies to improve the level of functioning and quality of life.

Background First‐pass effect (FPE), that is, achieving reperfusion with a single thrombectomy device pass, is associated with better clinical outcomes in patients with acute stroke. FPE is therefore increasingly used as a marker of device and procedural efficacy. We aimed to evaluate the ability of thrombus‐based radiomics models to predict FPE in patients undergoing endovascular thrombectomy and compare performance with experts and nonradiomics thrombus characteristics. Methods Patients with thin‐slice noncontrast computed tomography and computed tomography angiography from the ESCAPE‐NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial were included. Thrombi were manually segmented on all images. Data were randomly split into a derivation set that included a training and a validation subset and an independent test set. Radiomics features were extracted from the derivation set. The machine learning models were compared with 3 expert stroke physicians in predicting FPE in the test set using area under the receiver operating characteristic curves. Results Thin‐slice images of 554 patients were divided into a derivation set (training [n=388] and validation [n=55]) and a test set (n=111). A radiomics model using the combination of noncontrast computed tomography, computed tomography angiography, and noncontrast computed tomography–computed tomography angiography difference achieved the highest performance (area under the curve, 0.74 [95% CI, 0.64–0.84]) for prediction of FPE. This was higher than the mean area under the curve of the 3 experts (0.62 [95% CI, 0.53–0.71], P=0.01 for difference in area under the curves). The radiomics model also performed better than nonradiomics‐based thrombus features such as volume and permeability measurements in predicting FPE (P

Background Patients with white matter disease (WMD) – a key marker of cerebral small vessel disease – may have less brain reserve to cope with ischemic injury. The relationship of WMD to functional recovery after endovascular thrombectomy is uncertain. We aim to explore the association between WMD and functional outcome, assessed at multiple time‐points postendovascular thrombectomy. Methods In this post hoc analysis, we analyzed noncontrast computed tomography‐imaging from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial and assessed WMD by using the total Fazekas‐score (score range: 0–6). The primary outcome was repeated measurements of the modified Rankin scale (mRS) scores (i.e., day‐5/discharge, day‐30, and day‐90). Secondary outcome measures were the ordinal‐mRS at 90‐days, 90‐day‐mRS0–2, and 90‐day‐mortality. Mixed‐linear and binary/ordinal logistic regressions were performed, adjusting for age, sex, baseline National Institutes of Health Stroke Scale, cortical atrophy, chronic infarctions, stroke laterality, follow‐up infarct volume, and alteplase–nerinetide interaction. Sensitivity analyses were done including only those patients for whom magnetic resonance imaging was available. Results We included 1102 patients with noncontrast computed tomography (median age 71, interquartile range: 61–80; median National Institutes of Health Stroke Scale 17, interquartile range: 12–21). The median total Fazekas‐score was 1(interquartile range: 0–2). Out of 1202 patients, 566 had follow‐up magnetic resonance imaging. We observed heterogeneity in functional recovery with varying degrees of WMD‐burden (P

Introduction The risk of hemorrhagic transformation (HT) in the early phase of acute ischemic stroke (AIS) remains unknown, leading to potential unnecessary delays in initiation of anticoagulation for secondary stroke prevention. We sought to assess the rate of HT associated withdirect oral anticoagulant (DOAC) initiation within and beyond 48 hours after AIS, using a pooled analysis of available published data. Methods A pooled analysis of 6 studies (4 prospective observational blinded outcome studies and2 randomized trials) of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted. The primary endpoint was incident radiographic HT on follow‐up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, mortality within the study period, and follow‐up modified Rankin Scale score.The results were reported as odds ratio (OR) andhazard ratio (HR)with 95% confidence interval (CI). Results We evaluated 509 patients; median infarct volume was1.5 (0.1‐7.8) ml, andmedian National Institutes of Health Stroke Scale was2 (0‐3).Incident radiographic HT was seen on follow‐up scan in 34 (6.8%) patients.DOAC initiation within 48 hours from index event was not associated with incident HT (adjusted OR 0.67, [0.30 – 1.50]P = 0.32).No patients developed symptomatic HT.Conversely, 31 (6.1%) patients developedrecurrent ischemic events, 64% of which occurred within 14 days.Initiating a DOAC within 48 hours of onset was associated with a trend towards lower rates of recurrent ischemic events, but this was not statistically significant (HR 0.42, [0.17 – 1.008]P = 0.052). In contrast to HT,recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84 – 16.24], p< 0.001). Conclusions Initiation of DOAC within 48 hours after stroke was not associated with decreased risk of recurrent ischemic events, or increasedincident risk of HT. Both recurrent ischemic events and incident HT occurred at similar rates.Unlike HT, however, recurrent ischemic events were associated with poor outcomes.

Introduction Endovascular therapy (EVT) is the standard‐of‐care for large vessel occlusion stroke; however, timely access to treatment is still limited for a large proportion of the population. Telerobotic EVT has the potential to decrease time to treatment and expand existing networks of care to more rural populations. It is currently unclear how its implementation would impact existing stroke networks. Methods Conditional probability models were generated to predict the probability of excellent outcome (modified Rankin Scale 0–1 at 90 days post stroke) for patients with suspected large vessel occlusion (LVO). A baseline stroke network was created for California using existing intravenous thrombolysis (IVT) centers and comprehensive stroke centers (CSCs) capable of IVT and EVT. Optimal transport decisions and catchment areas were generated for the baseline model and three hypothetical scenarios through conversion of IVT centers at various distances from a CSC into centers capable of Telerobotic EVT [i.e. hospitals ≥ 15 and < 50 miles from a CSC were converted (Scenario 1), ≥ 50 and < 100 miles (Scenario 2), and ≥ 100 miles (Scenario 3)]. Catchment areas were calculated for each scenario using varied robotic procedural delay times and success rates. Results In the baseline model, 51 hospitals were designated as CSCs and 142 hospitals were designated IVT centers. Conversion of IVT centers into Telerobotic EVT centers decreased median travel time for LVO patients in all three scenarios. The estimated number of robotically treated LVOs per year in Scenarios 1, 2, and 3 were 2172, 740, and 212, respectively. Scenario 1 (15‐50 miles) was the most sensitive to robotic time delay and success rate, but all three scenarios were more sensitive to decreases in procedural success rate compared to time delay. Conclusions Telerobotic EVT has the potential to improve care for stroke patients outside of major urban centers. Compared to procedural time delays in robotic EVT, a decrease in procedural success rate would not be well tolerated. This modeling analysis can inform system planning for the potential advent of remote EVT care.

Introduction The current neurovascular research funding environment is highly competitive, stifling collaboration and hindering progress. Further, specific groups of researchers/research topics are disproportionately affected, resulting in inequity in the funding process. These include early‐career researchers, women, and researchers from low‐middle income countries. Certain conditions, e.g., rare, stroke‐related diseases are due to their low prevalence not suitable for clinical trials, and therefore even less likely to receive funding. Currently, there is no easy way for people working on such topics to come together and collaborate. To address this problem, a novel internet‐based platform, Collavidence (www.collavidence.com), was designed. The idea is to complement current systems of neurovascular research collaboration and funding for more inclusive, efficient, and impactful research results. The aim of this study is to present the initial performance of the platform in achieving this goal. Methods Analytics on pre‐defined user‐, project‐, and interaction‐based metrics will be performed to describe the level of platform engagement in the initial months following launch. These include the number of users and projects posted, the amount of funding accumulated, the proportion of successfully funded projects, and the iterative improvement of the proposals. Further, the relative engagement of early‐career, female researchers, and researchers from low‐middle‐income countries will be assessed. Results A qualitative assessment of the value of the overall platform, the process of iterative review, and possibilities for collaboration will be presented. Further, trends in platform engagement during the initial 3 months, including the relative distribution of specific user demographics to assess the platform’s success in encouraging equity, diversity, and inclusion, will be presented. Conclusions This study will assess the feasibility and initial success of Collavidence as a unique platform for neurovascular research collaboration and funding.

IntroductionLong-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS), but occult AF is also found in some individuals without a stroke history and in patients with stroke of a known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal vs. incidental.MethodsThrough a systematic search, we identified all case–control and cohort studies applying identical long-term monitoring techniques to both patients with CS and KS. We performed a random-effects meta-analysis across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients and across age subgroups. We then applied Bayes' theorem to determine the probability that occult AF is causal or incidental.ResultsThe systematic search identified three case–control and cohort studies enrolling 560 patients (315 CS, 245 KS). Methods of long-term monitoring were implantable loop recorder in 31.0%, extended external monitoring in 67.9%, and both in 1.2%. Crude cumulative rates of AF detection were CS 47/315 (14.9%) vs. KS 23/246 (9.3%). In the formal meta-analysis, the summary odds ratio for occult AF in CS vs. KS in all patients was 1.80 (95% CI, 1.05–3.07), p = 0.03. With the application of Bayes' theorem, the corresponding probabilities indicated that, when present, occult AF in patients with CS is causal in 41.2% (95% CI, 15.5–77.7%) of patients. Analyses stratified by age suggested that detected occult AF in patients with CS was causal in 62.3% (95 CI, 0–87.1%) of patients under the age of 65 years and 28.5% (95 CI, 0–63.7%) of patients aged 65 years and older but estimates had limited precision.ConclusionCurrent evidence is preliminary, but it indicates that in cryptogenic stroke when occult AF is found, it is causal in about 41.2% of patients. These findings suggest that anticoagulation therapy may be beneficial to prevent recurrent stroke in a substantial proportion of patients with CS found to have occult AF.

ABSTRACTThe COVID-19 pandemic highlighted global interdependencies, accompanied by widespread calls for worldwide cooperation against a virus that knows no borders, but responses were led largely separately by national governments. In this tension between aspiration and reality, people began to grapple with how their own lives were affected by the global nature of the pandemic. In this article, based on 493 qualitative interviews conducted between 2020 and 2021, we explore how people in Argentina, Austria, Bolivia, Ecuador, Ireland, Italy and Mexico experienced, coped with and navigated the global nature of the pandemic. In dialogue with debates about the parameters of the ‘global’ in global health, we focus on what we call people's everyday (de)bordering practices to examine how they negotiated (dis)connections between ‘us’ and ‘them’ during the pandemic. Our interviewees’ reactions moved from national containment to an increasing focus on people's unequal socio-spatial situatedness. Eventually, they began to (de)border their lives beyond national lines of division and to describe a new normal: a growing awareness of global connectedness and a desire for global citizenship. This newfound sense of global interrelatedness could signal support for and encourage transnational political action in times of crises.

Background: It is not known if initial reductions in hospitalization for stroke and myocardial infarction early during the coronavirus disease–2019 pandemic were followed by subsequent increases. We describe the rates of emergency department visits for stroke and myocardial infarction through the pandemic phases. Methods: We used linked administrative data to compare the weekly age- and sex-standardized rates of visits for stroke and myocardial infarction in Ontario, Canada in the first 9 months of 2020 to the mean baseline rates (2015-2019) using rate ratios (RRs) and 95% confidence intervals (CIs). We compared care and outcomes by pandemic phases (pre-pandemic was January-March, lockdown was March-May, early reopening was May-July, and late reopening was July-September). Results: We identified 15,682 visits in 2020 for ischemic stroke (59.2%; n = 9279), intracerebral hemorrhage (12.2%; n = 1912), or myocardial infarction (28.6%; n = 4491). The weekly rates for stroke visits in 2020 were lower during the lockdown and early reopening than at baseline (RR 0.76, 95% CI [0.66, 0.87] for the largest weekly decrease). The weekly rates for myocardial infarction visits were lower during the lockdown only (RR 0.61, 95% CI [0.46, 0.77] for the largest weekly decrease), and there was a compensatory increase in visits following reopening. Ischemic stroke 30-day mortality was increased during the lockdown phase (11.5% pre-coronavirus disease; 12.2% during lockdown; 9.2% during early reopening; and 10.6% during late reopening, P = 0.015). Conclusion: After an initial reduction in visits for stroke and myocardial infarction, there was a compensatory increase in visits for myocardial infarction. The death rate after ischemic stroke was higher during the lockdown than in other phases. Résumé: Contexte: Nous ignorons si les réductions des taux d'hospitalisations pour un AVC et un infarctus du myocarde observées au début de la pandémie de coronavirus de 2019 ont été suivies d'une hausse de ces taux. Nous décrivons ici les taux de visites aux services des urgences pour un AVC et un infarctus du myocarde pendant toutes les phases de la pandémie. Méthodes: À partir de données administratives couplées, nous comparons les taux hebdomadaires de visites pour un AVC et un infarctus du myocarde, normalisés en fonction de l’âge et du sexe, en Ontario, au Canada, effectuées pendant les neuf premiers mois de 2020, avec les taux moyens de base (2015-2019), en utilisant des ratios des taux (RR) et des intervalles de confiance (IC) à 95 %. Nous avons comparé les soins et les issues selon les phases de la pandémie (avant la pandémie : de janvier à mars; confinement : de mars à mai; début de la réouverture : de mai à juillet; phase tardive de la réouverture : de juillet à septembre). Résultats: Nous avons répertorié 15 682 visites effectuées en 2020 pour un AVC ischémique (59,2 %; n = 9 279), une hémorragie intracérébrale (12,2 %; n = 1 912) ou un infarctus du myocarde (28,6 %; n = 4 491). Les taux hebdomadaires de visites pour un AVC effectuées en 2020 étaient inférieurs pendant la période de confinement et le début de la réouverture comparativement à la période de base (RR : 0,76; IC à 95 % : 0,66-0,87 pour la plus grande baisse hebdomadaire). Les taux hebdomadaires de visites pour un infarctus du myocarde étaient inférieurs pendant la période de confinement seulement (RR : 0,61; IC à 95 % : 0,46-0,77 pour la baisse hebdomadaire la plus importante); une hausse compensatrice du nombre de visites a été notée après la réouverture. Le taux de mortalité à 30 jours des suites d'un AVC ischémique était plus élevé pendant la période de confinement (11,5 % avant la pandémie de coronavirus; 12,2 % pendant le confinement; 9,2 % au début de la période de réouverture; 10,6 % pendant la phase tardive de la réouverture, p = 0,015). Conclusion: Après une réduction initiale du nombre de visites motivées par un AVC et un infarctus du myocarde, on a noté une hausse compensatrice du nombre de visites motivées par un infarctus du myocarde. Le taux de mortalité des suites d'un AVC ischémique était plus élevé pendant la période de confinement que pendant les autres périodes.

Background and Purpose Various imaging paradigms are used for endovascular treatment (EVT) decision-making and outcome estimation in acute ischemic stroke (AIS). We aim to compare how these imaging paradigms perform for EVT patient selection and outcome estimation. Methods Prospective multi-center cohort study of patients with AIS symptoms with multi-phase computed tomography angiography (mCTA) and computed tomography perfusion (CTP) baseline imaging. mCTA-based EVT-eligibility was defined as presence of large vessel occlusion (LVO) and moderate-to-good collaterals on mCTA. CTP-based eligibility was defined as presence of LVO, ischemic core (defined on relative cerebral blood flow, absolute cerebral blood flow, and cerebral blood volume maps) 1.8, absolute mismatch >15 mL. EVT-eligibility and adjusted rates of good outcome (modified Rankin Scale 0–2) based on these imaging paradigms were compared. Results Of 289/464 patients with LVO, 263 (91%) were EVT-eligible by mCTA-criteria versus 63 (22%), 19 (7%) and 103 (36%) by rCBF, aCBF, and CBV-CTP-criteria. CTP and mCTA-criteria were discordant in 40% to 53%. Estimated outcomes were best in patients who met both mCTA and CTP eligibility-criteria and were treated with EVT (62% to 87% good outcome). Patients eligible for EVT by mCTA-criteria and not by CTP-criteria receiving EVT achieved good outcome rates of 53% to 57%. Few patients met CTP-criteria and not mCTA-criteria for EVT. Conclusions Simpler imaging selection criteria that rely on little else than detection of the occluded blood vessel may be more sensitive and less specific, thus resulting in more patients being offered EVT and arguably benefiting from it.

Background Although the association between cortical venous opacification (VO) and clinical outcomes has been shown in previous studies, little is known about the relationship between parenchymal hemorrhage (PH) and VO in patients with acute stroke. We aimed to determine whether cortical VO assessed on computed tomography angiography correlates with the risk of PH following endovascular treatment. Methods This is a post hoc analysis of the ESCAPE NA‐1 (Efficacy and Safety of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial. Control‐arm patients with adequate venous assessment on computed tomography angiography were included. Any PH and symptomatic intracranial hemorrhage were compared between patients with poor VO (cortical vein opacification score

Background Intravenous thrombolysis with alteplase is widely used in patients with acute ischemic stroke presenting early after symptom onset. Recent phase II trials have suggested that intravenous tenecteplase may be safer and associated with higher early reperfusion rates as compared with alteplase. This study investigates whether intravenous tenecteplase is noninferior to intravenous alteplase for the treatment of acute ischemic stroke. Methods This is a pragmatic, registry‐linked, prospective, randomized (1:1) controlled, open‐label parallel group clinical trial (AcT [Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke]) with blinded end point assessment of 1600 patients to test if intravenous tenecteplase (0.25 mg/kg body weight, maximum dose 25 mg) is noninferior to intravenous alteplase (0.9 mg/kg body weight; maximum dose, 90 mg) in patients with acute ischemic stroke eligible for intravenous thrombolysis in clinical routine. Patients are recruited from comprehensive and primary stroke centers and enrolled using deferral of consent. The proposed sample has at least 90% power with a noninferiority margin of 5%, assuming incidence of the 90‐day modified Rankin Scale score of 0 to 1 is 38% in the tenecteplase and 35% in the alteplase groups, and a loss to follow‐up rate

Abstract Background There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months). Methods We will recruit 264 participants (aged 50–80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months). Discussion This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing. Trial registration ClinicalTrials.gov NCT03035851 . Registered on 30 January 2017

Abstract Cerebral artery morphological alterations have been associated with several cerebrovascular and neurological diseases, whereas these structures are known to be highly variable among healthy individuals. To date, the knowledge about the influence of cardiovascular risk factors on the morphology of cerebral arteries is rather limited. The aim of this work was to investigate the impact of cardiovascular risk factors on the regional cerebroarterial radius and density. Time-of-Flight magnetic resonance angiography from 1722 healthy adults (21–82 years) were used to extract region-specific measurements describing the main cerebral artery morphology. Multivariate statistical analysis was conducted to quantify the impact of cardiovascular risk factors, including clinical and life behavioural factors, on each region-specific artery measurement. Increased age, blood pressure, and markers of obesity were significantly associated with decreased artery radius and density in most regions, with aging having the greatest impact. Additionally, females showed significantly higher artery density while males showed higher artery radius. Smoking and alcohol consumption did not show any significant association with the artery morphology. The results of this study improve the understanding of the impact of aging, clinical factors, and life behavioural factors on cerebrovascular morphology and can help to identify potential risk factors for cerebrovascular and neurological diseases.

Background Health state utility values are commonly used to provide summary measures of health‐related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post‐stroke quality of life. Methods and Results We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health‐related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ‐5D‐3L, EQ‐5D‐5L, AQoL, HUI2, HUI3, 15D, and SF‐6D using random effects models. For the EQ‐5D‐3L we conducted stratified meta‐analyses and meta‐regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ‐5D‐3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ‐5D‐3L at ≥3 months following stroke was 0.65 (95% CI, 0.63–0.67), which was ≈20% below population norms. There was high heterogeneity (I2>90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ‐5D‐3L estimates. Conclusions Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration URL: https://www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42020215942.

Background and Purpose Multiphase computed tomographic angiography (mCTA) provides time variant images of pial vasculature supplying brain in patients with acute ischemic stroke (AIS). To develop a machine learning (ML) technique to predict tissue perfusion and infarction from mCTA source images. Methods 284 patients with AIS were included from the Precise and Rapid assessment of collaterals using multi-phase CTA in the triage of patients with acute ischemic stroke for Intra-artery Therapy (Prove-IT) study. All patients had non-contrast computed tomography, mCTA, and computed tomographic perfusion (CTP) at baseline and follow-up magnetic resonance imaging/non-contrast-enhanced computed tomography. Of the 284 patient images, 140 patient images were randomly selected to train and validate three ML models to predict a pre-defined Tmax thresholded perfusion abnormality, core and penumbra on CTP. The remaining 144 patient images were used to test the ML models. The predicted perfusion, core and penumbra lesions from ML models were compared to CTP perfusion lesion and to follow-up infarct using Bland-Altman plots, concordance correlation coefficient (CCC), intra-class correlation coefficient (ICC), and Dice similarity coefficient. Results Mean difference between the mCTA predicted perfusion volume and CTP perfusion volume was 4.6 mL (limit of agreement [LoA], –53 to 62.1 mL; P=0.56; CCC 0.63 [95% confidence interval [CI], 0.53 to 0.71; P

Abstract Background Robotic rehabilitation after stroke provides the potential to increase and carefully control dosage of therapy. Only a small number of studies, however, have examined robotic therapy in the first few weeks post-stroke. In this study we designed robotic upper extremity therapy tasks for the bilateral Kinarm Exoskeleton Lab and piloted them in individuals with subacute stroke. Pilot testing was focused mainly on the feasibility of implementing these new tasks, although we recorded a number of standardized outcome measures before and after training. Methods Our team developed 9 robotic therapy tasks to incorporate feedback, intensity, challenge, and subject engagement as well as addressing both unimanual and bimanual arm activities. Subacute stroke participants were assigned to a robotic therapy (N = 9) or control group (N = 10) in a matched-group manner. The robotic therapy group completed 1-h of robotic therapy per day for 10 days in addition to standard therapy. The control group participated only in standard of care therapy. Clinical and robotic assessments were completed prior to and following the intervention. Clinical assessments included the Fugl-Meyer Assessment of Upper Extremity (FMA UE), Action Research Arm Test (ARAT) and Functional Independence Measure (FIM). Robotic assessments of upper limb sensorimotor function included a Visually Guided Reaching task and an Arm Position Matching task, among others. Paired sample t-tests were used to compare initial and final robotic therapy scores as well as pre- and post-clinical and robotic assessments. Results Participants with subacute stroke (39.8 days post-stroke) completed the pilot study. Minimal adverse events occurred during the intervention and adding 1 h of robotic therapy was feasible. Clinical and robotic scores did not significantly differ between groups at baseline. Scores on the FMA UE, ARAT, FIM, and Visually Guided Reaching improved significantly in the robotic therapy group following completion of the robotic intervention. However, only FIM and Arm Position Match improved over the same time in the control group. Conclusions The Kinarm therapy tasks have the potential to improve outcomes in subacute stroke. Future studies are necessary to quantify the benefits of this robot-based therapy in a larger cohort. Trial registration: ClinicalTrials.gov, NCT04201613, Registered 17 December 2019—Retrospectively Registered, https://clinicaltrials.gov/ct2/show/NCT04201613 .

Background In light of evidence from recent trials that endovascular thrombectomy (EVT) alone may potentially be noninferior to combined treatment, that is, with intravenous thrombolysis (IVT) with alteplase and EVT, we sought to understand physician and patient preferences around this issue. Methods We conducted a 2‐stage mixed methods study that included a structured, international, web‐based cross‐sectional survey among stroke physicians, and a focus group involving stroke survivors and caregivers. Demographic information was collected from all participants. The survey offered multiple choice questions and options to respond via free text which was analyzed quantitatively. The focus group was conducted online and analyzed qualitatively using a grounded theory approach. Results A total of 225 physicians (67% men) from 44 countries completed the survey. Most participants (70%) were between 31 and 50 years of age. Survey results showed that in current practice, 90% respondents would offer IVT to patients with large vessel occlusion stroke eligible for both IVT and EVT. When asked if their practice would change in light of recent trials, 63% responded no. When asked about the appropriate timing for IVT in the setting of large vessel occlusion stroke with EVT availability, 56% preferred to administer IVT immediately, 21% were willing to defer the decision for 30 minutes from groin puncture, and 8% were willing to defer for 60 minutes from groin puncture to assess if reperfusion was achieved with EVT. A total of 61% participants would choose to use tenecteplase over alteplase as the preferred drug for IVT if both drugs are backed by evidence. The focus group identified a need to better understand patient characteristics that may benefit from EVT‐only or combined strategies. The focus group also identified the need for more data to inform physician decision making. Conclusions Most physicians surveyed prefer IVT before EVT in patients with acute ischemic stroke attributable to large vessel occlusion, although there was some uncertainty around this issue. The need for further studies, including data on IVT with tenecteplase and among various patient subgroups to inform decision making, was apparent from both the survey and the patient focus group.

Background: The literature indicates that cardiovascular disease (CVD; including stroke), older age, and availability of health care resources affect COVID-19 case fatality rates (CFRs). The cumulative effect of COVID-19 CFRs in global CVD populations and the extrapolated effect on access to health care services in the CVD population in Canada are not fully known. In this study we explored the relationships of factors that might affect COVID-19 CFRs and estimated the potential indirect effects of COVID-19 on Canadian health care resources. Methods: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFRs and: (1) the proportion of the population with CVD; (2) the proportion of the population 65 years of age or older; and (3) the availability of essential health services as defined by the World Health Organization Universal Health Coverage index. For indirect implications on health care resources, estimates of the volume of postponed coronary artery bypass grafting, percutaneous coronary intervention, and valve surgeries in Ontario were calculated. Results: Positive correlations were found between COVID-19 CFRs and: (1) the proportion of the population with CVD (ρ = 0.40; P = 0.001); (2) the proportion of the population 65 years of age or older (ρ = 0.43; P = 0.0005); and (3) Universal Health Coverage index (ρ = 0.27; P = 0.03). For every 1% increase in the proportion of the population 65 years of age or older or proportion of the population with CVD, the COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1252 procedures would be postponed monthly in Ontario because of current public health measures. Conclusions: Countries with more prevalent CVD reported higher COVID-19 CFRs. Strain on health care resources is likely in Canada. Résumé: Contexte: La littérature indique que les maladies cardiovasculaires (MCV, incluant les accidents vasculaires cérébraux), l’âge avancé et la facilité d’accès aux ressources de soins de santé ont une incidence sur les taux de létalité (TL) des cas de COVID-19. L’effet cumulatif du TL de la COVID-19 dans l’ensemble de la population atteinte de MCV et l’impact anticipé sur l'accès aux services de santé dans la population atteinte de MCV au Canada ne sont pas entièrement connus. Cette étude a exploré les liens entre les facteurs pouvant influencer le TL des cas de COVID-19 et a estimé le potentiel impact indirect de la COVID-19 sur les ressources de soins de santé au Canada. Méthodes: Les données épidémiologiques à l’échelle du pays ont été analysées pour étudier la corrélation, l’effet principal et l’interaction entre le TL de laCOVID-19 et : 1) la proportion de la population souffrant de MCV, 2) la proportion de la population ≥ 65 ans, et 3) l’accessibilité des services de santé essentiels tels que définis par l’indice de couverture sanitaire universelle (CSU) de l’Organisation Mondiale de la Santé. Pour les implications indirectes concernant les ressources de santé, des estimations du volume d’opération de pontages coronariens, d'interventions coronariennes percutanées et de chirurgies valvulaires reportées en Ontario ont été calculées. Résultats: Des corrélations positives ont été trouvées entre le TL de la COVID-19 et 1) la proportion de la population souffrant de MCV (ρ= 0,40, P = 0,001), 2) la proportion de la population ≥ 65 ans (ρ= 0,43, P = 0,0005), et 3) l’indice CSU (ρ= 0,27, P = 0,03). Pour chaque augmentation de 1 % de la proportion de la population ≥ 65 ans ou de la proportion de la population souffrant de MCV, le TL de la COVID-19 était respectivement supérieur de 9 % et 19 %. Environ 1 252 interventions seraient reportées chaque mois en Ontario en raison des mesures de santé publique actuelles. Conclusions: Les pays où les MCV sont plus répandues ont signalé un TL de la COVID-19 plus élevé. Il est probable que les ressources de soins de santé soient soumises à de fortes contraintes au Canada.

Peripartum cardiomyopathy (PPCM) is a rare but potentially fatal disease. The management of PPCM is individualized, and an early diagnosis is instrumental in the institution of an appropriate management plan. Here, we present a dramatic case of PPCM that was managed with a period of mechanical circulatory support. (Level of Difficulty: Beginner.)

Abstract Physical inactivity is a leading modifiable risk factor for cardiovascular and cerebrovascular disease, cognitive dysfunction, and global mortality. Regular exercise might mitigate age‐related declines in cardiovascular and cerebrovascular function. In this study, we hypothesize that a 6‐month aerobic exercise intervention will lead to a decrease in cerebrovascular resistance index (CVRi) and to an increase in cerebral blood flow (CBF) and cerebrovascular conductance index (CVCi) during two submaximal exercise workloads (40% VO2max and 65 W), intensities that have been shown to be comparable to activities of daily life. Two hundred three low‐active healthy men and women enrolled in the Brain in Motion study, completed a 6‐month exercise intervention and underwent submaximal and maximal tests pre‐/post‐intervention. The intervention improved the gas exchange threshold and maximal oxygen consumption (VO2max), with no change in heart rate at VO2max, during the treadmill VO2max test. Heart rate and CVRi decreased from pre‐intervention values during both relative (40% VO2max) and absolute (65 W) submaximal exercise tests. Blood flow velocity in the middle cerebral artery and CVCi increased post‐intervention during 40% VO2max and 65 W. Changes in mean arterial pressure were found only during the absolute component (65 W). Our study demonstrates that aerobic exercise improves not only cardiorespiratory indices but also cerebrovascular function at submaximal workloads which may help to mitigate age‐related declines in everyday life. Investigation of the mechanisms underlying the decline in cardiovascular and cerebrovascular capacity with aging has important implications for the maintenance of health and continued independence of older adults.

Background Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. Methods Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared using the area under the receiver operating characteristic curve (AUC). Shapley values were used to determine marginal contributions of variables to outcome variance in the regression models. Results Among 1105 patients, functional independence was achieved by 666 (60.3%). When using baseline variables only (model 1), the AUC was 0.74 (95% CI, 0.71–0.77); this iteratively improved when treatment and posttreatment variables were added to the models (model 2: AUC, 0.77; 95% CI, 0.74–0.80; model 3: AUC, 0.80; 95% CI, 0.77–0.83; model 4: AUC, 0.82; 95% CI, 0.79–0.85). With baseline variables alone, 26% of patients who achieved functional independence were erroneously classified as not achieving functional independence. Even with the most comprehensive model, 19.8% of patients were misclassified as such. Patient age contributed most to outcome variance (Shapley value, 0.28), followed by severe adverse events including pneumonia (0.16) and intracranial hemorrhage at 24‐hours imaging (0.13). Conclusions A substantial contribution to outcomes after endovascular therapy comes from factors unrelated to currently collected baseline patient variables. One‐fifth of patients achieving functional independence were misclassified as not achieving independence, even with the most comprehensive model. Our findings suggest that the achievable accuracy of current outcome prediction models is limited, and caution should be used when applying them in clinical practice.

The benefit of acute ischemic stroke (AIS) treatment is highly time dependent. Although studies on workflow improvement in AIS are increasingly gaining attention, there is a lack of consensus and consistency regarding the definition, measurement, and reporting of AIS workflow times. We discuss the challenges related to defining and measuring workflow times in AIS and propose a basic set of time intervals that should be reported in AIS workflow studies. We particularly focus on patients undergoing mechanical thrombectomy. Importantly, endovascular treatment workflow times should always be reported in conjunction with reperfusion quality because one is not informative without the other. We further suggest standardized reporting of workflow times that includes the 90th percentile in addition to medians and interquartile ranges, means, and SDs. The proposed methodology serves as a framework for AIS studies and aids further discussion on workflow‐related AIS research.

Background: Direct teleconsultations between emergency medical services (EMS) crews and hospital-based stroke neurologists are mandated in the Czech Republic as triage and prenotification tool in acute stroke patients. The main aim of this study was to analyze the efficacy as well as quality of such teleconsultations in daily clinical practice.Methods: This is a descriptive analysis of teleconsultations between EMS paramedic crews and hospital-based neurologists in a geographically defined region of the Czech Republic (Moravian-Silesian region) between October 2018 to December 2018. All teleconsultations were analyzed for length and content. Content analysis included the following information: date, age, sex, prehospital neurological deficit(s), known/unknown time of symptom onset, anticoagulation status, vital signs, premorbid disability, and patient ID/insurance company number.Results: Within the study period, paramedics conducted 522 calls across 6 stroke centers. Of these, 334 (64%) calls were conducted because patients met pre-established prehospital criteria for suspected acute stroke. Median call duration was 1 min 44 s ± 56 s (minimum 50 s, maximum 5 min 5 s). Amongst the analyzed prehospital teleconsultations, stroke onset time was reported in 95% of cases, neurological deficit in 96%, significant co-morbidities in 53%, premorbid disability in 37%, and anticoagulation status in 53%.Conclusion: Teleconsultations between paramedics and hospital-based neurologists are not time-consuming. Stroke onset time and severity of neurological deficit are consistently communicated, however other important information such as comorbidities, premorbid disability, and anticoagulation status are reported inconsistently.

Infarct volume (FIV) on follow-up diffusion-weighted imaging (FU-DWI) is only moderately associated with functional outcome in acute ischemic stroke patients. However, FU-DWI may contain other imaging biomarkers that could aid in improving outcome prediction models for acute ischemic stroke. We included FU-DWI data from the HERMES, ISLES, and MR CLEAN-NO IV databases. Lesions were segmented using a deep learning model trained on the HERMES and ISLES datasets. We assessed the performance of three classifiers in predicting functional independence for the MR CLEAN-NO IV trial cohort based on: (1) FIV alone, (2) the most important features obtained from a trained convolutional autoencoder (CAE), and (3) radiomics. Furthermore, we investigated feature importance in the radiomic-feature-based model. For outcome prediction, we included 206 patients: 144 scans were included in the training set, 21 in the validation set, and 41 in the test set. The classifiers that included the CAE and the radiomic features showed AUC values of 0.88 and 0.81, respectively, while the model based on FIV had an AUC of 0.79. This difference was not found to be statistically significant. Feature importance results showed that lesion intensity heterogeneity received more weight than lesion volume in outcome prediction. This study suggests that predictions of functional outcome should not be based on FIV alone and that FU-DWI images capture additional prognostic information.