Stroke risk in women with atrial fibrillation.

BACKGROUND AND AIMS: Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. METHODS: Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. RESULTS: The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. CONCLUSION: Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.

Exploring the Inclusion of Person-Centered Care Domains in Stroke Transitions of Care Interventions: A Scientific Statement From the American Heart Association.

BACKGROUND: Health care teams along the stroke recovery continuum have a responsibility to support care transitions and return to the community. Ideally, individualized care will consider patient and family preferences, best available evidence, and health care professional input. Person-centered care can improve patient-practitioner interactions through shared decision-making in which health professionals and institutions are sensitive to those for whom they provide care. However, it is unclear how the concepts of person-centered care have been described in reports of stroke transitional care interventions. METHODS: A secondary analysis of a systematic review and meta-analysis was undertaken. We retrieved all included articles (n=17) and evaluated the extent to which each intervention explicitly addressed 7 domains of person-centered care: alignment of care with patients' values, preferences, and needs; coordination of care; information and education; physical comfort; emotional support; family and friend involvement; and smooth transition and continuity of care. RESULTS: Most of the articles included some aspects of person-centeredness; we found that certain domains were not addressed in the descriptions of transitional care interventions, and no articles mentioned all 7 domains of person-centered care. We identified 3 implications for practice and research: (1) delineating person-centered care components when reporting interventions, (2) elucidating social and cultural factors relevant to the study sample and intervention, and (3) clearly describing the role of family and nonmedical support in the intervention. CONCLUSIONS: There is still room for greater consistency in the reporting of person-centeredness in stroke transitions of care interventions, despite a long-standing definition and conceptualization of person-centered care in academic and clinically focused literature.

No association between metformin initiation and incident dementia in older adults newly diagnosed with diabetes.

BACKGROUND: Metformin has been suggested to reduce dementia risk; however, most epidemiologic studies have been limited by immortal time bias or confounding due to disease severity. OBJECTIVES: To investigate the association of metformin initiation with incident dementia using strategies that mitigate these important sources of bias. METHODS: Residents of Ontario, Canada ≥66 years newly diagnosed with diabetes from January 1, 2008 to December 31, 2017 entered this retrospective population-based cohort. To consider the indication for metformin monotherapy initiation, people with hemoglobin A1c of 6.5%-8.0% and estimated glomerular filtration rate ≥45 mL/min/1.73 m2 were selected. Using the landmark method to address immortal time bias, exposure was grouped into "metformin monotherapy initiation within 180 days after new diabetes diagnosis" or "no glucose-lowering medications within 180 days." To address disease latency, 1-year lag time was applied to the end of the 180-day landmark period. Incident dementia was defined using a validated algorithm for Alzheimer's disease and related dementias. Adjusted hazard ratios (aHR) and confidence intervals (CIs) were estimated from propensity-score weighted Cox proportional hazard models. RESULTS: Over mean follow-up of 6.77 years from cohort entry, metformin initiation within 180 days after new diabetes diagnosis (N = 12,331; 978 events; 65,762 person-years) showed no association with dementia risk (aHR [95% CI] = 1.05 [0.96-1.15]), compared to delayed or no glucose-lowering medication initiation (N = 22,369; 1768 events; 117,415 person-years). CONCLUSION: Early metformin initiation was not associated with incident dementia in older adults newly diagnosed with diabetes. The utility of metformin to prevent dementia was not supported.

Seasonal Variations in Stroke Occurrence.

BACKGROUND: Understanding seasonal variations in stroke can help stakeholders identify underlying causes in seasonal trends, and tailor resources appropriately to times of highest needs. We sought to evaluate the seasonal occurrence of stroke and its subtypes. METHODS: We conducted a retrospective cohort study using administrative data from January 1st, 2003, to December 31st, 2017, in Ontario, Canada's most populous province. We evaluated seasonal variations in stroke occurrence by subtype, via age/sex standardized rates and adjusted rate ratios using Poisson regressions. In those with stroke, we evaluated 30-day case fatality risks by season, adjusted for age, sex, stroke type, and comorbid conditions, and then used Cox proportional hazard models to estimate the effect of season on the fatality. The administrative data used in this study were from the Canadian Institute for Health Information's Discharge Abstract Database, the National Ambulatory Care Reporting System Database, the Ontario Registered Persons Database, and the 2006 and 2011 Canada Census and linked administrative databases. RESULTS: During our study period, we observed 394,145 strokes or TIA events, with a decrease in monthly hospitalization/emergency department visits per 100,000 people between January 2003 and December 2017 from 24.22 to 17.43. Compared to the summer, overall stroke occurrence was similar in the spring but slightly lower in the fall (adjusted rate ratio [aRR] 0.97, 95% confidence interval [CI] 0.96-0.98) and winter (aRR 0.94, 95% CI: 0.94-0.95). There were minor variations by stroke subtype. Winter was associated with the highest risk of stroke case fatality compared to the summer (12.4% vs. 11.4%, adjusted hazard ratio 1.10, 95% CI: 1.07-1.13). CONCLUSIONS: We found seasonal variations in stroke occurrence and case fatality, although the absolute differences were small. Further work is needed to better understand how environmental or meteorological factors might affect stroke risk.

Age-Specific Association of Co-Morbidity With Home-Time After Acute Stroke.

OBJECTIVE: To examine the association of co-morbidity with home-time after acute stroke and whether the association is influenced by age. METHODS: We conducted a province-wide study using linked administrative databases to identify all admissions for first acute ischemic stroke or intracerebral hemorrhage between 2007 and 2018 in Alberta, Canada. We used ischemic stroke-weighted Charlson Co-morbidity Index of 3 or more to identify those with severe co-morbidity. We used zero-inflated negative binomial models to determine the association of severe co-morbidity with 90-day and 1-year home-time, and logistic models for achieving ≥ 80 out of 90 days of home-time, assessing for effect modification by age and adjusting for sex, stroke type, comprehensive stroke center care, hypertension, atrial fibrillation, year of study, and separately adjusting for estimated stroke severity. We also evaluated individual co-morbidities. RESULTS: Among 28,672 patients in our final cohort, severe co-morbidity was present in 27.7% and was associated with lower home-time, with a greater number of days lost at younger age (-13 days at age < 60 compared to -7 days at age 80+ years for 90-day home-time; -69 days at age < 60 compared to -51 days at age 80+ years for 1-year home-time). The reduction in probability of achieving ≥ 80 days of home-time was also greater at younger age (-22.7% at age < 60 years compared to -9.0% at age 80+ years). Results were attenuated but remained significant after adjusting for estimated stroke severity and excluding those who died. Myocardial infarction, diabetes, and cancer/metastases had a greater association with lower home-time at younger age, and those with dementia had the greatest reduction in home time. CONCLUSION: Severe co-morbidity in acute stroke is associated with lower home-time, more strongly at younger age.

Validation of the Passive Surveillance Stroke Severity Score in Three Canadian Provinces.

BACKGROUND: Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada. METHODS: We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. 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. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (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 admission to long-term care (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 increased the c-statistics compared to models without this variable. CONCLUSION: PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Kenton Award Lecture-Stroke Disparities Research: Learning From the Past, Planning for the Future.

Inequities in stroke care and outcomes have been documented both within and among countries based on factors, such as race, geography, and socioeconomic status. Research can help us to identify, understand, and address inequities, and this article offers considerations for scientists working in this area. These include designing research aimed at identifying the underlying causes of inequities, recognizing the importance of the social determinants of health, considering interventions that go beyond the individual patient and provider to include policies and systems, acknowledging the role of structural racism, performing community-engaged participatory research, considering intersecting social identities, learning from cross-national comparisons, maintaining the data sources needed for inequities research, using terminology that advances health equity, and improving diversity across the research enterprise.

Stroke in Women and Unique Risk Factors.

There has been a plethora of studies focused on female-specific risk factors and sex differences in stroke published in the past year. This article summarizes several of those novel studies which provide new knowledge about the field of stroke in women. The Nurses' Health Study II provides new data on the association between laparoscopically proven endometriosis and future stroke, accounting for the mediation effects of hysterectomy and oophorectomy. In a cohort of women from China, the relationship between hysterectomy, oophorectomy, and stroke is further clarified, accounting for the age at which the procedure is performed. The UK Biobank study provides new information on the relationship between oral contraceptive and hormone replacement therapy and stroke, with analytical techniques that focus on the timing of events related to duration of exposure. Finally, 2 new meta-analyses address the question of whether sex differences exist in the presentation of stroke symptoms.

Attributable Costs of Stroke in Ontario, Canada and Their Variation by Stroke Type and Social Determinants of Health.

BACKGROUND: Estimates of attributable costs of stroke are scarce, as most prior studies do not account for the baseline health care costs in people at risk of stroke. We estimated the attributable costs of stroke in a universal health care setting and their variation across stroke types and several social determinants of health. METHODS: We undertook a population-based administrative database-derived matched retrospective cohort study in Ontario, Canada. Community-dwelling adults aged ≥40 years with a stroke between 2003 and 2018 were matched (1:1) on demographics and comorbidities with controls without stroke. Using a difference-in-differences approach, we estimated the mean 1-year direct health care costs attributable to stroke from a public health care payer perspective, accounting for censoring with a weighted available sample estimator. We described health sector-specific costs and reported variation across stroke type and social determinants of health. RESULTS: The mean 1-year attributable costs of stroke were Canadian dollars 33 522 (95% CI, $33 231-$33 813), with higher costs for intracerebral hemorrhage ($40 244; $39 193-$41 294) than ischemic stroke ($32 547; $32 252-$32 843). Most of these costs were incurred in acute care hospitals ($15 693) and rehabilitation facilities ($7215). Compared with all patients with stroke, the mean attributable costs were higher among immigrants ($40 554; $39 316-$41 793), those aged <65 years ($35 175; $34 533-$35 818), and those residing in low-income neighborhoods ($34 687; $34 054-$35 320) and lower among rural residents ($29 047; $28 362-$29 731). CONCLUSIONS: Our findings of high attributable costs of stroke, especially in immigrants, younger patients, and residents of low-income neighborhoods, can be used to evaluate potential health care cost savings associated with different primary stroke prevention strategies.

Previous Ischemic Stroke Significantly Alters Stroke Risk in Newly Diagnosed Cancer Patients.

BACKGROUND: Previous ischemic stroke (IS) is a risk factor for subsequent IS in the general population; it is unclear if this relationship remains true in patients with cancer. Our objective was to examine the association between previous IS and risk for future IS in individuals newly diagnosed with cancer. METHODS: We conducted a retrospective population-based matched cohort study of newly diagnosed adult cancer patients (excluding nonmelanoma skin cancers and primary central nervous system tumors) in Ontario, Canada from 2010 to 2020; those with prior IS were matched (1:4) by age, sex, year of cancer diagnosis, cancer stage, and cancer site to those without a history of stroke. Cumulative incidence function curves were created to estimate the incidence of IS. Subdistribution adjusted hazard ratios (aHRs) and 95% CIs were calculated, where death was treated as a competing event. Multivariable analysis was adjusted for imbalanced baseline characteristics. RESULTS: We examined 65 525 individuals with cancer, including 13 070 with a history of IS. The median follow-up duration was 743 days (interquartile range, 177-1729 days). The incidence of IS following cancer diagnosis was 261.3/10 000 person-years in the cohort with prior IS and 75.3/10 000 person-years in those without prior IS. Individuals with prior IS had an increased risk for IS after cancer diagnosis compared with those without a history (aHR, 2.68 [95% CI, 2.41-2.98]); they also had more prevalent cardiovascular risk factors. The highest risk for stroke compared with those without a history of IS was observed in the gynecologic cancer (aHR, 3.84 [95% CI, 2.15-6.85]) and lung cancer (aHR, 3.18 [95% CI, 2.52-4.02]) subgroups. The risk of IS was inversely correlated with lag time of previous stroke; those with IS 1 year before their cancer diagnosis had the highest risk (aHR, 3.68 [95% CI, 3.22-4.22]). CONCLUSIONS: Among individuals with newly diagnosed cancer, those with IS history were almost 3× more likely to experience a stroke after cancer diagnosis, especially if the prediagnosis stroke occurred within 1 year preceding cancer diagnosis.

Maternal Health Outcomes After Pregnancy-Associated Stroke: A Population-Based Study With 19 Years of Follow-Up.

BACKGROUND: Pregnancy-associated stroke carries high short-term morbidity and mortality, but data on subsequent maternal outcomes are limited. We evaluated long-term maternal health outcomes after pregnancy-associated stroke. METHODS: In this retrospective cohort study, we used administrative data to identify pregnant adults aged ≤49 years with stroke between 2002-2020 in Ontario, Canada and 2 comparison groups: (1) non-pregnant female patients with stroke and (2) pregnant patients without stroke. Patients who survived the index admission were followed until 2021. After propensity score matching, we used Cox regression with a robust variance estimator to compare pregnant patients with stroke and the 2 comparison groups for the composite outcome of death and all-cause non-pregnancy readmission. Where proportional hazard assumption was not met, we reported time-varying hazard ratios (HR) with 95% CIs by modeling the log-hazard ratio as a function of time using restricted cubic splines. RESULTS: We identified 217 pregnant patients with stroke, 7604 non-pregnant patients with stroke, and 1 496 256 pregnant patients without stroke. Of the 202 pregnant patients with stroke who survived the index stroke admission, 41.6% (6.8 per 100 person-years) subsequently died or were readmitted during follow-up. Median follow-up times were 5 years (pregnancy-associated stroke), 3 years (non-pregnant stroke), and 8 years (pregnant without stroke). Pregnant patients with stroke had a lower hazard of death and all-cause readmission compared with non-pregnant patients with stroke at 1-year follow-up (HR, 0.64 [95% CI, 0.44-0.94]), but this association did not persist during longer-term follow-up. Conversely, pregnant patients with stroke had higher hazard of death and readmission compared with pregnant patients without stroke at 1-year follow-up (HR, 5.70 [95% CI, 3.04-10.66]), and this association persisted for a decade. CONCLUSIONS: Stroke during pregnancy is associated with long-term health consequences. It is essential to transition care postpartum to primary or specialty care to optimize vascular health.

Change in Hospital Risk-standardized Stroke Mortality Performance With and Without the Passive Surveillance Stroke Severity Score.

BACKGROUND: Adjustment for baseline stroke severity is necessary for accurate assessment of hospital performance. We evaluated whether adjusting for the Passive Surveillance Stroke SeVerity (PaSSV) score, a measure of stroke severity derived using administrative data, changed hospital-specific estimated 30-day risk-standardized mortality rate (RSMR) after stroke. METHODS: We used linked administrative data to identify adults who were hospitalized with ischemic stroke or intracerebral hemorrhage across 157 hospitals in Ontario, Canada between 2014 and 2019. We fitted a random effects logistic regression model using Markov Chain Monte Carlo methods to estimate hospital-specific 30-day RSMR and 95% credible intervals with adjustment for age, sex, Charlson comorbidity index, and stroke type. In a separate model, we additionally adjusted for stroke severity using PaSSV. Hospitals were defined as low-performing, average-performing, or high-performing depending on whether the RSMR and 95% credible interval were above, overlapping, or below the cohort's crude mortality rate. RESULTS: We identified 65,082 patients [48.0% were female, the median age (25th,75th percentiles) was 76 years (65,84), and 86.4% had an ischemic stroke]. The crude 30-day all-cause mortality rate was 14.1%. The inclusion of PaSSV in the model reclassified 18.5% (n=29) of the hospitals. Of the 143 hospitals initially classified as average-performing, after adjustment for PaSSV, 20 were reclassified as high-performing and 8 were reclassified as low-performing. Of the 4 hospitals initially classified as low-performing, 1 was reclassified as high-performing. All 10 hospitals initially classified as high-performing remained unchanged. CONCLUSION: PaSSV may be useful for risk-adjusting mortality when comparing hospital performance. External validation of our findings in other jurisdictions is needed.

External Validation of the Passive Surveillance Stroke Severity Indicator.

BACKGROUND: The Passive Surveillance Stroke Severity (PaSSV) Indicator was derived to estimate stroke severity from variables in administrative datasets but has not been externally validated. METHODS: We used linked administrative datasets to identify patients with first hospitalization for acute stroke between 2007-2018 in Alberta, Canada. We used the PaSSV indicator to estimate stroke severity. We used Cox proportional hazard models and evaluated the change in hazard ratios and model discrimination for 30-day and 1-year case fatality with and without PaSSV. Similar comparisons were made for 90-day home time thresholds using logistic regression. We also linked with a clinical registry to obtain National Institutes of Health Stroke Scale (NIHSS) and compared estimates from models without stroke severity, with PaSSV, and with NIHSS. RESULTS: There were 28,672 patients with acute stroke in the full sample. In comparison to no stroke severity, addition of PaSSV to the 30-day case fatality models resulted in improvement in model discrimination (C-statistic 0.72 [95%CI 0.71-0.73] to 0.80 [0.79-0.80]). After adjustment for PaSSV, admission to a comprehensive stroke center was associated with lower 30-day case fatality (adjusted hazard ratio changed from 1.03 [0.96-1.10] to 0.72 [0.67-0.77]). In the registry sample (N = 1328), model discrimination for 30-day case fatality improved with the inclusion of stroke severity. Results were similar for 1-year case fatality and home time outcomes. CONCLUSION: Addition of PaSSV improved model discrimination for case fatality and home time outcomes. The validity of PASSV in two Canadian provinces suggests that it is a useful tool for baseline risk adjustment in acute stroke.

Association of co-morbidity with acute stroke mortality by age and time since stroke: A population-based study.

OBJECTIVE: To examine whether the association of co-morbidity with mortality after acute stroke is influenced by stroke type, age, sex, or time since stroke. MATERIALS AND METHODS: We conducted a province-wide population-based study using linked administrative databases to identify all admissions for acute stroke between 2007-2018 in Alberta, Canada. We used Cox proportional hazard models to determine the association of severe co-morbidity based on the Charlson Co-morbidity Index with 1-year mortality after stroke, assessing for effect modification by stroke type, age, and sex, and with adjustment for estimated stroke severity, comprehensive stroke centre care, hypertension, atrial fibrillation, and year of study. We used a piecewise model to analyze the impact of co-morbidity across four time periods. RESULTS: We had 28,672 patients in our final cohort (87.8% ischemic stroke). The hazard of mortality with severe co-morbidity was higher for individuals with ischemic stroke (adjusted hazard ratio [aHR] 2.20, 95% CI 2.07-2.32) compared to those with intracerebral hemorrhage (aHR 1.70, 95% CI 1.51-1.92; pint<0.001), and higher in individuals under age 75 (aHR 3.20, 95% CI 2.90-3.53) compared to age ≥75 (aHR 1.93, 95% CI 1.82-2.05, pint<0.001). There was no interaction by sex. The hazard ratio increased in a graded fashion at younger ages and was higher after the first 30 days of acute stroke. CONCLUSION: There was a stronger association between co-morbidity and mortality at younger age and in the subacute phase of stroke. Further research is needed to determine the reason for these findings and identify ways to improve outcomes among those with stroke and co-morbid conditions at young age.

Intravenous Thrombolysis After First-Ever Ischemic Stroke and Reduced Incident Dementia Rate.

BACKGROUND: The use of intravenous thrombolysis is associated with improved clinical outcomes. Whether thrombolysis is associated with reduced incidence of poststroke dementia remains uncertain. We sought to estimate if the use of thrombolysis following first-ever ischemic stroke was associated with a reduced rate of incident dementia using a pragmatic observational design. METHODS: We included first-ever ischemic stroke patients from the Ontario Stroke Registry who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained by a validated diagnostic algorithm. We employed inverse probability of treatment-weighted Cox proportional hazard models to estimate the cause-specific hazard ratio for the association of thrombolysis and incident dementia at 1 and 5 years following stroke. RESULTS: From July 2003 to March 2013, 7072 patients with ischemic stroke were included, 3276 (46.3%) were female and mean age was 71.0 (SD, 12.8) years. Overall, 38.2% of the cohort (n=2705) received thrombolysis, 77.2% (n=2087) of which was administered within 3 hours of stroke onset. In the first year following stroke, thrombolysis administration was associated with a 24% relative reduction in the rate of developing dementia (cause-specific hazard ratio, 0.76 [95% CI, 0.58-0.97]). This association remained significant at 5 years (cause-specific hazard ratio, 0.79 [95% CI, 0.66-0.91]) and at the end of follow-up (median 6.3 years; cause-specific hazard ratio, 0.79 [95% CI, 0.68-0.89]). CONCLUSIONS: Thrombolysis administration following first-ever ischemic stroke was independently associated with a reduced rate of dementia. Incident dementia should be considered as a relevant outcome when evaluating risk/benefit of thrombolysis in ischemic stroke patients.

Towards better reporting of the proportion of days covered method in cardiovascular medication adherence: A scoping review and new tool TEN-SPIDERS.

Although medication adherence is commonly measured in electronic datasets using the proportion of days covered (PDC), no standardized approach is used to calculate and report this measure. We conducted a scoping review to understand the approaches taken to calculate and report the PDC for cardiovascular medicines to develop improved guidance for researchers using this measure. After prespecifying methods in a registered protocol, we searched Ovid Medline, Embase, Scopus, CINAHL Plus and grey literature (1 July 2012 to 14 December 2020) for articles containing the terms "proportion of days covered" and "cardiovascular medicine", or synonyms and subject headings. Of the 523 articles identified, 316 were reviewed in full and 76 were included (93% observational studies; 47% from the USA; 2 grey literature articles). In 45 articles (59%), the PDC was measured from the first dispensing/claim date. Good adherence was defined as 80% PDC in 61 articles, 56% of which contained a rationale for selecting this threshold. The following parameters, important for deriving the PDC, were often not reported/unclear: switching (53%), early refills (45%), in-hospital supplies (45%), presupply (28%) and survival (7%). Of the 46 articles where dosing information was unavailable, 59% reported how doses were imputed. To improve the transparent and systematic reporting of the PDC, we propose the TEN-SPIDERS tool, covering the following PDC parameters: Threshold, Eligibility criteria, Numerator and denominator, Survival, Presupply, In-hospital supplies, Dosing, Early Refills, and Switching. Use of this tool will standardize reporting of the PDC to facilitate reliable comparisons of medication adherence estimates between studies.

Secular trends of ischaemic heart disease, stroke, and dementia in high-income countries from 1990 to 2017: the Global Burden of Disease Study 2017.

BACKGROUND: We assessed secular trends in the burden of ischaemic heart disease (IHD), stroke, and dementia in the Organization for Economic Co-operation and Development (OECD) countries. METHODS: Using the Global Burden of Disease (GBD) Study 2017, we compared sex-specific and age-standardized rates of disability-adjusted life years (DALY); mortality, incidence, and prevalence of IHD and stroke; and dementia per 100,000 people, in the world, OECD countries, and Canada. RESULTS: From 1990 to 2017, the crude incidence number of IHD, stroke, and dementia increased 52%, 76%, and 113%, respectively. Likewise, the prevalence of IHD (75%), stroke (95%), and dementia (119%) increased worldwide. In addition during the study period, the crude global number of deaths of IHD increased 52%, stroke by 41%, and dementia by 146% (9, 6, and 3 million deaths in 2017, respectively). Despite an increase in the crude number of these diseases, the global age-standardized incidence rate of IHD, stroke, and dementia decreased by -27%, - 11%, and - 5%, respectively. Moreover, there was a decline in their age-standardized DALY rates (- 1.17%, - 1.32%, and - 0.23% per year, respectively) and death rates (- 1.29%, - 1.46%, and - 0.17% per year, respectively), with sharper downward trends in Canada and OECD countries. Almost all trends flattened during the last decade. CONCLUSIONS: From 1990 to 2017, the age-standardized burden of IHD, stroke, and dementia decreased, more prominently in OECD countries than the world. However, their rising crude numbers mainly due to population growth and ageing require urgent identification of reversible risk and protective factors.

Relationship of frailty with excess mortality during the COVID-19 pandemic: a population-level study in Ontario, Canada.

BACKGROUND: There is a paucity of the literature on the relationship between frailty and excess mortality due to the COVID-19 pandemic. METHODS: The entire community-dwelling adult population of Ontario, Canada, as of January 1st, 2018, was identified using the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) cohort. Residents of long-term care facilities were excluded. Frailty was categorized through the Johns Hopkins Adjusted Clinical Groups (ACG® System) frailty indicator. Follow-up was until December 31st, 2020, with March 11th, 2020, indicating the beginning of the COVID-19 pandemic. Using multivariable Cox models with patient age as the timescale, we determined the relationship between frailty status and pandemic period on all-cause mortality. We evaluated the modifier effect of frailty using both stratified models as well as incorporating an interaction between frailty and the pandemic period. RESULTS: We identified 11,481,391 persons in our cohort, of whom 3.2% were frail based on the ACG indicator. Crude mortality increased from 0.75 to 0.87% per 100 person years from the pre- to post-pandemic period, translating to ~ 13,800 excess deaths among the community-dwelling adult population of Ontario (HR 1.11 95% CI 1.09-1.11). Frailty was associated with a statistically significant increase in all-cause mortality (HR 3.02, 95% CI 2.99-3.06). However, all-cause mortality increased similarly during the pandemic in frail (aHR 1.13, 95% CI 1.09-1.16) and non-frail (aHR 1.15, 95% CI 1.13-1.17) persons. CONCLUSION: Although frailty was associated with greater mortality, frailty did not modify the excess mortality associated with the pandemic.

Stroke in Women.

Sex differences exist in the epidemiology, care, and outcomes of stroke. This article highlights recent advances in our understanding of sex and gender differences in the benefits of endovascular therapy, outcomes after stroke and transient neurological events, and the potential to prevent stroke in women with a history of hypertensive disorders of pregnancy.