Raed A. Joundi’s research while affiliated with McMaster University and other places

Background Health system disruptions since onset of the COVID-19 pandemic may have adversely impacted adherence to medications for common cardiovascular risk factors. Methods We examined adherence to and discontinuation of incident prescriptions for medications treating hypertension, dyslipidemia, diabetes, and atrial fibrillation in Ontario, Alberta, and Nova Scotia, Canada. We compared the recent period (April 1, 2020 through most recently available follow-up: September 30, 2021 for Ontario; March 31, 2021 for Alberta; and March 31, 2022 for Nova Scotia) to the baseline, pre-pandemic period (April 1, 2014 through March 31, 2019). In each province, people aged ≥66 years with a valid health number and corresponding incident prescription were included. For each medication class, adherence in the recent period, defined as ≥ 0.80 proportion-of-days-covered (PDC), was compared to the pre-pandemic period using modified Poisson regression with robust error variance, adjusted for patient characteristics. Similarly adjusted Cox proportional hazards models compared hazard of discontinuation over one year of follow-up between the two time periods. Results In the recent period, PDC ranged from 48.9% for dyslipidemia medications in Alberta to 82.2% for anticoagulants in Nova Scotia. Adherence was not different between periods, with the following exceptions: higher adherence in the recent period for antihypertensives (adjusted risk ratios [aRR] 1.08, 95% CI 1.06–1.10) and dyslipidemics (aRR 1.07, 95% CI 1.04–1.09) in Nova Scotia, and for antihyperglycemics (aRR 1.10, 95% CI 1.08–1.14) and anticoagulants (1.15, 95% CI 1.12, 1.18) in Alberta. Adherence was lower in the recent period only for antihypertensives in Alberta (aRR 0.95, 95% CI 0.93, 0.97). One-year rates of discontinuation ranged from 20.9% for anticoagulants in the Alberta recent period to 56.7% for antihypertensives in the Ontario baseline period. The adjusted hazard of discontinuation was lower or unchanged in the recent period for all medication classes. Conclusions Despite significant health system disruptions since 2020, recent adherence to incident cardiovascular prescriptions was similar or better than before and rates of medication discontinuation were lower. However, interventions are still needed to improve existing, suboptimal adherence.

Background: People with stroke are at high risk of dementia. There have been reductions in stroke case fatality and disability but temporal trends in the incidence and absolute burden of post-stroke dementia have not been described. Methods: We did a population-wide analysis of over 15 million people in Ontario, Canada between 2002-2022. Using linked administrative databases, we identified all 90-day dementia-free survivors of first acute ischemic stroke or intracerebral hemorrhage (ICH). We evaluated dementia incidence from 90-days after stroke onwards using a validated definition which included hospitalization, physician claims, and dementia medications. We calculated 1-year and 5-year incidence of dementia as percentages and per 100 person-years for each fiscal year, age-/sex-standardized by the 2002 population and with follow-up until March 2022. We stratified incidence trends by sex, stroke type, and severity (90-day home time of <60 days indicating moderate-severe stroke). We described trends in absolute number of people with post-stroke dementia, stratified by sex, and used linear regression to evaluate significance. Results: We identified 175,980 people with acute stroke surviving dementia-free to 90 days. From 2002-2021, there was modestly decreasing 1- and 5-year dementia incidence, primarily occurring from 2011 onwards (Figure 1). 5-year dementia decreased by an absolute change of -2.4% (15.5% to 13.1%) and a relative change of -15%. However, there was an increase in the number of people surviving with stroke (Figure 1A-B), so the absolute number of people with post-stroke dementia remained stable or increased over time (Figure 2). Women had higher age-standardized dementia incidence than men, but no difference in trends (Figure 3A-B). There was decreasing dementia incidence for ischemic stroke but no significant change for ICH (Figure 3C-D). Those with 90-day home time <60 days had twice the incidence of dementia compared to those with > 60 days, with no change over time (Figure 3E-F). Conclusion: In this large, population-wide study from 2002-2022, a modest decrease in post-stroke dementia incidence was offset by increasing numbers of stroke survivors and resulted in a rising absolute burden of post-stroke dementia. Those with more severe stroke had 2-fold higher dementia rate which did not change over time despite improvements in stroke care. New strategies are needed to address the persistent and increasing burden of post-stroke dementia.

Background Cerebral microbleeds are associated with an increased risk of hemorrhagic transformation (HT) following acute ischemic stroke. We investigated whether the effect of dabigatran (vs. aspirin) in patients with acute minor non-cardioembolic ischemic stroke/transient ischemic attack (TIA) is modified by baseline microbleeds on MRI. Methods The Dabigatran Treatment of Acute Stroke II trial randomized 305 patients with acute minor non-cardioembolic ischemic stroke/TIA to dabigatran (150/110 mg twice daily) or aspirin (81 mg daily) for 30 days. Microbleeds were centrally adjudicated in patients with an interpretable blood-sensitive sequence on baseline MRI. In this post hoc analysis, we used multivariable regression models to determine the association between microbleeds and any incident HT on day-30 MRI and excellent functional outcome (modified Rankin scale = 0–1) at 90 days. Results A total of 251 (82.3%) participants (mean age = 66 ± 13 years, 36% women, median [IQR] onset-to-randomization time = 40[27–55] hours; median [IQR] NIHSS = 1 [0–2]) were included, of whom 82 (33%) had microbleeds. On day-30 MRI, 6% ( n = 14) developed HT, and 80% ( n = 191) achieved 90-day mRS of 0–1. We found no association between microbleed presence and HT (adjusted OR = 0.84; 95%CI:0.21–3.25) or excellent functional outcome (adjusted RR = 1.09; 95%CI:0.94–1.26). The rate of HT in patients with microbleeds was 3% with dabigatran and 4% with aspirin (OR = 0.85; 95%CI:0.11–6.75). Excellent functional outcome occurred in 74% and 84% of dabigatran and aspirin-treated patients, respectively (RR = 0.88; 95%CI:0.69–1.12). The presence, severity or location of microbleeds did not modify the effect of dabigatran on these outcomes ( p -interaction > 0.05). Conclusions Early dabigatran treatment appears safe in patients with acute minor non-cardioembolic ischemic stroke/TIA and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI.

Background Collaborative research with end-users is an effective way to generate meaningful research applications and support greater impact on practice and knowledge exchange. To address these needs, a Citizen Advisory Group (CAG) of nine older adults (ages 64–80, 67% women) was formed to advise scientists on the development of Brain Health PRO (BHPro), a web-based platform designed to increase dementia prevention literacy and awareness. The current study evaluated if the CAG met its objectives, how inclusion of the CAG aligned with collaborative research approaches, and the CAG’s experience and satisfaction throughout the development process. Methods An anonymous online survey was administered to the CAG members and 30 scientist/trainee authors of the BHPro chapters. The CAG also participated in an online focus group. Results Most CAG members and chapter authors agreed that the CAG met its primary objectives and added unique value to BHPro. Both groups viewed the CAG’s involvement as well-aligned with engaged scholarship, co-production, integrated knowledge translation, and, to a lesser extent, participatory research practices. CAG members reported high satisfaction with personal goal attainment, which included learning, collaborating with others, and making a meaningful impact. Content analyses of the focus group revealed three categories: 1) personal benefits related to learning, connection, and feeling valued, 2) value of a masked peer-review process, and 3) an accessible final product. Conclusions Findings suggest that collaborating with end-users in the process of aging research confers personal and scientific benefits for both older adults and researchers.

Recovery trajectories in intracerebral hemorrhage (ICH) are recognized as distinct from those observed in ischemic stroke. This narrative review aims to clarify the pathophysiology underlying ICH recovery patterns, highlighting the unique timeline and nature of functional improvements seen in ICH survivors. Population-based cohort studies tracking functional outcomes in a longitudinal fashion, along with randomized clinical trial data with standardized outcome assessments, have demonstrated that ICH recovery generally has a delayed onset in the first weeks, followed by a steep early subacute stage recovery (typically up to 3 months) continuing in protracted, gradual improvements beyond 3 to 6 months. Understanding these recovery patterns, and how these differ from ischemic stroke, is crucial for providing accurate prognostic information, facilitating targeted health care delivery, and optimizing therapeutic interventions and the design of ICH randomized trials. This article synthesizes current evidence on early- and late-stage functional recovery trajectories in primary, spontaneous ICH and cognitive outcomes, emphasizing the clinical and research implications of these recovery patterns.

Background and objectives: Survivors of stroke are at high risk of dementia, but it is unclear whether this elevated risk is due to other confounding factors. We sought to determine the magnitude and time course of dementia risk after stroke with robust comparison with matched nonstroke populations in an entire province. Methods: We conducted a population-wide analysis of over 15 million people in Ontario, Canada, between 2002 and 2022. Using linked administrative databases, we identified adults hospitalized for ischemic stroke, intracerebral hemorrhage, or acute myocardial infarction (AMI). We performed 1:1 matching of people with stroke to all residents of Ontario (reference population) without stroke and separately to those with AMI, on age, sex, rural residence, neighborhood deprivation, and vascular comorbidities. We calculated the incident rate per 100 person-years and hazard ratios (HRs) for all-cause dementia between 90 days after stroke and 1 year, 5 years, 10 years, and total follow-up and evaluated time-varying HRs. In sensitivity analyses, we adjusted for new stroke in follow-up and the cumulative number of health care encounters. Results: Of 175,980 stroke survivors, 174,817 (99.3%) were successfully matched to people in the reference population and 151,673 (90%) were matched to those with AMI. Over a mean follow-up of 5.6 years (SD 4.71, maximum 20 years), a total of 32,621 (18.7%) were diagnosed with dementia after stroke compared with 21,929 (12.5%) in the Ontario reference population. The rate of dementia per 100 person-years over total follow-up time was higher after acute stroke compared with the reference population (3.34 vs 1.89) and the AMI cohort (3.19 vs 1.75). The HR of dementia was higher in those with stroke compared with the reference population (1.76, 95% CI 1.73-1.79) and the AMI cohort (1.82, 1.79-1.85). HRs varied across time, with over 2.5-fold increase in dementia risk within 1 year, decreasing to 1.5-fold at 5 years and 1.3-fold at 20 years after stroke. Estimates were similar in sensitivity analyses. Recurrent stroke was associated with 3-fold increased dementia risk. Discussion: In this population-wide study, almost one-fifth of stroke survivors were diagnosed with dementia, with an 80% higher risk of dementia after robust matching to those without stroke. Targeted dementia prevention efforts in acute and chronic survivors of stroke are needed.

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. ResultsWe 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 objectives: Home-time is a patient-prioritized stroke outcome that can be derived from administrative data linkages. The effect of faster time-to-treatment with endovascular thrombectomy (EVT) on home-time after acute stroke is unknown. Methods: We used the Quality Improvement and Clinical Research registry to identify a cohort of patients who received EVT for acute ischemic stroke between 2015 and 2022 in Alberta, Canada. We calculated days at home in the first 90 days after stroke. We used ordinal regression across 6 ordered categories of home-time to evaluate the association between onset-to-arterial puncture and higher home-time, adjusting for age, sex, rural residence, NIH Stroke Scale, comorbidities, intravenous thrombolysis, and year of treatment. We used restricted cubic splines to assess the nonlinear relationship between continuous variation in time metrics and higher home-time, and also reported the adjusted odds ratios within time categories. We additionally evaluated door-to-puncture and reperfusion times. Finally, we analyzed home-time with zero-inflated models to determine the minutes of earlier treatment required to gain 1 day of home-time. Results: We had 1,885 individuals in our final analytic sample. There was a nonlinear increase in home-time with faster treatment when EVT was within 4 hours of stroke onset or 2 hours of hospital arrival. There was a higher odds of achieving more days at home when onset-to-puncture time was <2 hours (adjusted odds ratio 2.36, 95% CI 1.77-3.16) and 2 to <4 hours (1.37, 95% CI 1.11-1.71) compared with ≥6 hours, and when door-to-puncture time was <1 hour (aOR 2.25, 95% CI 1.74-2.90), 1 to <1.5 hours (aOR 1.89, 95% CI 1.47-2.41), and 1.5 to <2 hours (1.35, 95% CI 1.04-1.76) compared with ≥2 hours. Results were consistent for reperfusion times. For every hour of faster treatment within 6 hours of stroke onset, there was an estimated increase in home-time of 4.7 days, meaning that approximately 1 day of home-time was gained for each 12.8 minutes of faster treatment. Discussion: Faster time-to-treatment with EVT for acute stroke was associated with greater home-time, particularly within 4 hours of onset-to-puncture and 2 hours of door-to-puncture time. Within 6 hours of stroke onset, each 13 minutes of faster treatment is associated with a gain of 1 day of home-time.

Importance The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown. Objective To assess the time-dependent association of EVT with self-reported quality of life in patients with acute ischemic stroke. Design, Setting, and Participants Data were used from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, which tested the effect of nerinetide on functional outcomes in patients with large vessel occlusion undergoing EVT and enrolled patients from March 1, 2017, to August 12, 2019. The ESCAPE-NA1 trial was an international randomized clinical trial that recruited patients from 7 countries. Patients with EuroQol 5-dimension 5-level (EQ-5D-5L) index values at 90 days and survivors with complete domain scores were included in the current study. Data were analyzed from July to September 2023. Exposure Hospital arrival to arterial puncture time and other time metrics. Main Outcomes and Measures EQ-5D-5L index scores were calculated at 90 days using country-specific value sets. The association between time from hospital arrival to EVT arterial-access (door-to-puncture) and EQ-5D-5L index score, quality-adjusted life years, and visual analog scale (EQ-VAS) were evaluated using quantile regression, adjusting for age, sex, stroke severity, stroke imaging, wake-up stroke, alteplase, and nerinetide treatment and accounting for clustering by site. Using logistic regression, the association between door-to-puncture time and reporting no or slight symptoms (compared with moderate, severe, or extreme problems) was determined in each domain (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) or across all domains. Time from stroke onset was also evaluated, and missing data were imputed in sensitivity analyses. Results Among 1105 patients in the ESCAPE-NA1 trial, there were 1043 patients with EQ-5D-5L index values at 90 days, among whom 147 had died and were given a score of 0, and 1039 patients (mean [SD] age, 69.0 [13.7] years; 527 male [50.7%]) in the final analysis as 4 did not receive EVT. There were 896 survivors with complete domain scores at 90 days. There was a strong association between door-to-puncture time and EQ-5D-5L index score (increase of 0.03; 95% CI, 0.02-0.04 per 15 minutes of earlier treatment), quality-adjusted life years (increase of 0.29; 95% CI, 0.08-0.49 per 15 minutes of earlier treatment), and EQ-VAS (increase of 1.65; 95% CI, 0.56-2.72 per 15 minutes of earlier treatment). Each 15 minutes of faster door-to-puncture time was associated with higher probability of no or slight problems in each of 5 domains and all domains concurrently (range from 1.86%; 95% CI, 1.14-2.58 for pain or discomfort to 3.55%; 95% CI, 2.06-5.04 for all domains concurrently). Door-to-puncture time less than 60 minutes was associated higher odds of no or slight problems in each domain, ranging from odds ratios of 1.49 (95% CI, 1.13-1.95) for pain or discomfort to 2.59 (95% CI, 1.83-3.68) for mobility, with numbers needed to treat ranging from 7 to 17. Results were similar after multiple imputation of missing data and attenuated when evaluating time from stroke onset. Conclusions and Relevance Results suggest that faster door-to-puncture EVT time was strongly associated with better health-related quality of life across all domains. These results support the beneficial impact of door-to-treatment speed on patient-reported outcomes and should encourage efforts to improve patient-centered care in acute stroke by optimizing in-hospital processes and workflows.