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Background: There are few large population-based studies of outcomes after subarachnoid hemorrhage (SAH) than other stroke types. Method(s): We pooled data from 13 population-based stroke incidence studies (10 studies from the INternational STRroke oUtComes sTudy (INSTRUCT) and 3 new studies; N=657). Primary outcomes were case-fatality and functional outcome (modified Rankin scale score 3-5 [poor] vs. 0-2 [good]). Harmonized patient-level factors included age, sex, health behaviours (e.g. current smoking at baseline), comorbidities (e.g.history of hypertension), baseline stroke severity (e.g. NIHSS >7) and year of stroke. We estimated predictors of case-fatality and functional outcome using Poisson regression and generalized estimating equations using log-binomial models respectively at multiple timepoints. Result(s): Case-fatality rate was 33% at 1 month, 43% at 1 year, and 47% at 5 years. Poor functional outcome was present in 27% of survivors at 1 month and 15% at 1 year. In multivariable analysis, predictors of death at 1-month were age (per decade increase MRR 1.14 [1.07-1.22]) and SAH severity (MRR 1.87 [1.50-2.33]); at 1 year were age (MRR 1.53 [1.34-1.56]), current smoking (MRR 1.82 [1.20-2.72]) and SAH severity (MRR 3.00 [2.06-4.33]) and; at 5 years were age (MRR 1.63 [1.45-1.84]), current smoking (MRR 2.29 [1.54-3.46]) and severity of SAH (MRR 2.10 [1.44-3.05]). Predictors of poor functional outcome at 1 month were age (per decade increase RR 1.32 [1.11-1.56]) and SAH severity (RR 1.85 [1.06-3.23]), and SAH severity (RR 7.09 [3.17-15.85]) at 1 year. Conclusion(s): Although age is a non-modifiable risk factor for poor outcomes after SAH, however, severity of SAH and smoking are potential targets to improve the outcomes.Copyright © 2021 Elsevier Inc.

Background: There is limited research on the provision of evidence-based care and its association with outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Aim(s): We examined adherence to evidence-based care after aSAH and associations with survival and discharge destination. Also, factors associated with evidence-based care including age, sex, Charlson comorbidity index, severity scores, and delayed cerebral ischemia and infarction were examined for association with survival and discharge destination. Method(s): In a retrospective cohort (2010-2016) of all aSAH cases across two comprehensive cerebrovascular centres, we extracted 3 indicators of evidence-based aSAH care from medical records: (1) antihypertensives prior to aneurysm treatment, (2) nimodipine, and (3) aneurysm treatment (coiling/clipping). We defined 'optimal care' as receiving all eligible processes of care. Survival at 1 year was obtained by data linkage. We estimated (1) proportion of patients and characteristics associated with receiving processes of care, (2) associations between processes of care with 1-year mortality using cox-proportional hazard model and discharge destination with log binomial regression adjusting for age, sex, severity of aSAH, delayed cerebral ischemia and/or cerebral infarction and comorbidities. Sensitivity analyses explored effect modification of the association between processes of care and outcome by management type (active versus comfort measures). Result(s): Among 549 patients (69% women), 59% were managed according to the guidelines. Individual indicators were associated with lower 1-year mortality but not discharge destination. Optimal care reduced mortality at 1 year in univariable (HR 0.24 95% CI 0.17-0.35) and multivariable analyses (HR 0.51 95% CI 0.34-0.77) independent of age, sex, severity, comorbidities, and hospital network. Conclusion(s): Adherence to processes of care reduced 1-year mortality after aSAH. Many patients with aSAH do not receive evidenc

Background and Purpose-Women are reported to have poorer health-related quality of life (HRQoL) after stroke than men, but the underlying reasons are uncertain. We investigated factors contributing to the sex differences. Methods-Individual participant data on 4288 first-ever strokes (1996-2013) were obtained from 4 high-quality population-based incidence studies from Australasia and Europe. HRQoL utility scores among survivors after stroke (range from negative scores=worse than death to 1=perfect health) were calculated from 3 scales including European Quality of Life-5 Dimensions, Short-Form 6-Dimension, and Assessment of Quality of Life at 1 year (3 studies; n=1210) and 5 years (3 studies; n=1057). Quantile regression was used to estimate the median differences in HRQoL for women compared to men with adjustment for covariates. Study factors included sociodemographics, prestroke dependency, stroke-related factors (eg, stroke severity), comorbidities, and poststroke depression. Study-specific median differences were combined into pooled estimates using random-effect meta-analysis. Results-Women had lower pooled HRQoL than men (median differenceunadjusted 1 year,-0.147; 95% CI,-0.258 to-0.036; 5 years,-0.090; 95% CI,-0.119 to-0.062). After adjustment for age, stroke severity, prestroke dependency, and depression, these pooled median differences were attenuated, more greatly at 1 year (-0.067; 95% CI,-0.111 to-0.022) than at 5 years (-0.085; 95% CI,-0.135 to-0.034). Conclusions-Women consistently exhibited poorer HRQoL after stroke than men. This was partly attributable to women's advanced age, more severe strokes, prestroke dependency, and poststroke depression, suggesting targets to reduce the differences. There was some evidence of residual differences in HRQoL between sexes but they were small and unlikely to be clinically significant.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Background: Women are over-represented in aSAH cohorts, but whether their outcomes differ to men remains unclear. We examined if sex differences in neurological complications and aneurysm characteristics contributed to aSAH outcomes. Method(s): In a retrospective cohort (2010-2016) of all aSAH cases across two hospital networks in Australia, information on severity, aneurysm characteristics and neurological complications (rebleed before/after treatment, postoperative stroke < 48 h, neurological infections, hydrocephalus, seizures, delayed cerebral ischemia [DCI], cerebral infarction) were extracted. We estimated sex differences in (1) complications and aneurysm characteristics using chi square/t-tests and (2) outcome at discharge (home, rehabilitation or death) using multinomial regression with and without propensity score matching on prestroke confounders. Result(s): Among 577 cases (69% women, 84% treated) aneurysm size was greater in men than women and DCI more common in women than men. In unadjusted log multinomial regression, women had marginally greater discharge to rehabilitation (RRR 1.15 95% CI 0.90-1.48) and similar likelihood of in-hospital death (RRR 1.02 95% CI 0.76-1.36) versus discharge home. Prestroke confounders (age, hypertension, smoking status) explained greater risk of death in women (rehabilitation RRR 1.13 95% CI 0.87-1.48; death RRR 0.75 95% CI 0.51-1.10). Neurological complications (DCI and hydrocephalus) were covariates explaining some of the greater risk for poor outcomes in women (rehabilitation RRR 0.87 95% CI 0.69-1.11; death RRR 0.80 95% CI 0.52-1.23). Results were consistent in propensity score matched models. Conclusion(s): The marginally poorer outcome in women at discharge was partially attributable to prestroke confounders and complications. Improvements in managing complications could improve outcomes.Copyright © 2020, Springer-Verlag GmbH Austria, part of Springer Nature.

Background--Women have worse outcomes after stroke than men, and this may be partly explained by stroke severity. We examined factors contributing to sex differences in severity of acute stroke assessed by the National Institutes of Health Stroke Scale. Methods and Results--We pooled individual participant data with National Institutes of Health Stroke Scale assessment (N=6343) from 8 population-based stroke incidence studies (1996-2014), forming part of INSTRUCT (International Stroke Outcomes Study). Information on sociodemographics, stroke-related clinical factors, comorbidities, and pre-stroke function were obtained. Within each study, relative risk regression using log-binominal modeling was used to estimate the female:male relative risk (RR) of more severe stroke (National Institutes of Health Stroke Scale>7) stratified by stroke type (ischemic stroke and intracerebral hemorrhage). Study-specific unadjusted and adjusted RRs, controlling for confounding variables, were pooled using random-effects meta-analysis. National Institutes of Health Stroke Scale data were recorded in 5326 (96%) of 5570 cases with ischemic stroke and 773 (90%) of 855 participants with intracerebral hemorrhage. The pooled unadjusted female:male RR for severe ischemic stroke was 1.35 (95% CI 1.24-1.46). The sex difference in severity was attenuated after adjustment for age, pre-stroke dependency, and atrial fibrillation but remained statistically significant (pooled RRadjusted 1.20, 95% CI 1.10-1.30). There was no sex difference in severity for intracerebral hemorrhage (RRcrude 1.08, 95% CI 0.97-1.21; RRadjusted 1.08, 95% CI 0.96-1.20). Conclusions--Although women presented with more severe ischemic stroke than men, much although not all of the difference was explained by pre-stroke factors. Sex differences could potentially be ameliorated by strategies to improve pre-stroke health in the elderly, the majority of whom are women. Further research on the potential biological origin of sex dif

Objective: To examine factors contributing to the sex differences in functional outcomes and participation restriction after stroke. Method(s): Individual participant data on long-term functional outcome or participation restriction (i.e., handicap) were obtained from 11 stroke incidence studies (1993-2014). Multivariable log-binomial regression was used to estimate the female:male relative risk (RR) of poor functional outcome (modified Rankin Scale score >2 or Barthel Index score <20) at 1 year (10 studies, n = 4,852) and 5 years (7 studies, n = 2,226). Multivariable linear regression was used to compare the mean difference (MD) in participation restriction by use of the London Handicap Scale (range 0-100 with lower scores indicating poorer outcome) for women compared to men at 5 years (2 studies, n = 617). For each outcome, study-specific estimates adjusted for confounding factors (e.g., sociodemographics, stroke-related factors) were combined with the use of random-effects meta-analysis. Result(s): In unadjusted analyses, women experienced worse functional outcomes after stroke than men (1 year: pooled RRunadjusted 1.32, 95% confidence interval [CI] 1.18-1.48; 5 years: RRunadjusted 1.31, 95% CI 1.16-1.47). However, this difference was greatly attenuated after adjustment for age, prestroke dependency, and stroke severity (1 year: RRadjusted 1.08, 95% CI 0.97-1.20; 5 years: RR adjusted 1.05, 95% CI 0.94-1.18). Women also had greater participation restriction than men (pooled MDunadjusted -5.55, 95% CI -8.47 to -2.63), but this difference was again attenuated after adjustment for the aforementioned factors (MDadjusted -2.48, 95% CI -4.99 to 0.03). Conclusion(s): Worse outcomes after stroke among women were explained mostly by age, stroke severity, and prestroke dependency, suggesting these potential targets to improve the outcomes after stroke in women.Copyright © 2018 American Academy of Neurology.

Introduction: As women suffer worse functional outcomes of stroke than men, they may also face more challenges with community reintegration but data are scarce. We examined sex differences in participation after stroke and which factors might account for these disparities. Method(s): INSTRUCT is an individual participant data pooling study of incident strokes obtained from 13 population-based cohorts worldwide. Two of the cohorts (Melbourne '96-'99 and Auckland '02-'03) included assessment of participation at 5 years after stroke using the London Handicap Scale (LHS). The LHS is used to assess the individual's perspective of their involvement in life situations including orientation (person's awareness of surroundings), physical independence, mobility, occupation, social interaction and economic self-efficiency. The total score ranges from 0 (worst disadvantage) to 100 (no disadvantage). Linear regression was used to compare LHS total scores and sub-domains for women compared to men. Study-specific multivariable models incorporated adjustment for socio-demographics, stroke-related factors, pre-stroke health and post-stroke factors were combined using random-effects meta-analysis. Result(s): At 5 years after stroke, there were data on participation for 351/592 (59%) of survivors in Melbourne and 266/881 (30%) of survivors in Auckland. Women suffered greater participation restriction than men (total LHS, pooled mean difference, MD-5.55 [95% CI-8.47, 2.63]). The magnitude of the difference attenuated after adjusting for covariates (pooled MD-2.48 [4.99, 0.03]). Significant confounders in study-specific models included age, stroke severity, pre-stroke dependency and pre-stroke dementia for Melbourne; and age, stroke severity and pre-stroke dependency for Auckland. In sub-dimensions, women had greater restriction than men in mobility, physical independence and occupation. Additionally, women in Melbourne experienced poorer social integration and orientation than men. Con

Background - Women are reported to have greater mortality after stroke than men, but the reasons are uncertain. We examined sex differences in mortality at 1 and 5 years after stroke and identified factors contributing to these differences. Methods and Results - Individual participant data for incident strokes were obtained from 13 population-based incidence studies conducted in Europe, Australasia, South America, and the Caribbean between 1987 and 2013. Data on sociodemographics, stroke-related factors, prestroke health, and 1- and 5-year survival were obtained. Poisson modeling was used to estimate the mortality rate ratio (MRR) for women compared with men at 1 year (13 studies) and 5 years (8 studies) after stroke. Study-specific adjusted MRRs were pooled to create a summary estimate using random-effects meta-analysis. Overall, 16 957 participants with first-ever stroke followed up at 1 year and 13 216 followed up to 5 years were included. Crude pooled mortality was greater for women than men at 1 year (MRR 1.35; 95% confidence interval, 1.24-1.47) and 5 years (MRR 1.24; 95% confidence interval, 1.12-1.38). However, these pooled sex differences were reversed after adjustment for confounding factors (1 year MRR, 0.81; 95% confidence interval, 0.72-0.92 and 5-year MRR, 0.76; 95% confidence interval, 0.65-0.89). Confounding factors included age, prestroke functional limitations, stroke severity, and history of atrial fibrillation. Conclusions - Greater mortality in women is mostly because of age but also stroke severity, atrial fibrillation, and prestroke functional limitations. Lower survival after stroke among the elderly is inevitable, but there may be opportunities for intervention, including better access to evidence-based care for cardiovascular and general health.Copyright © 2017 American Heart Association, Inc.

Introduction: It is uncertain why women suffer worse long-term outcomes after stroke than men. We examined sex differences in mortality and disability 1 and 5 years after stroke and identified factors contributing to these differences. Method(s): Individual patient data pooling study of incident strokes (ischemic and hemorrhagic) from 1987-2013 obtained from 12 population-based cohorts from Australasia, Europe, South America and the Caribbean. Data on socio-demographics, stroke-related factors and pre-stroke health were obtained for each patient and harmonized between studies. Poisson modelling estimated the mortality rate ratio (MRR) for women compared to men at 1 year (12 studies) and 5 years (7 studies) post-stroke. Log binomial regression estimated the relative risk (RR) of poor outcome (modified Rankin scale>2 or Barthel Index <20) for women compared to men at 1 year (9 studies) and 5 years (6 studies) after stroke. Multivariable models were adjusted for potential confounders including age, pre-stroke dependency, stroke severity and comorbidities. Result(s): A total of 16557 first-ever-stroke patients with follow-up data to 1 year and 12,839 with follow-up to 5 years were included. The pooled crude mortality was greater in women than men at 1-year (MRR 1.37 95% CI 1.27-1.48) and 5 years (MRR 1.25 95% CI 1.13-1.39). However, these sex differences were reversed after adjustment for confounders at both 1 year (MRR 0.94 95% CI 0.82-1.06) and 5-years post stroke (MRR 0.74 95% CI 0.66-0.84). Similarly, the pooled crude RR for disability after stroke was greater in women than men at 1-year (RR 1.28 95% CI 1.17-1.39 and 5-year (RR 1.32 95% CI 1.18-1.47), but these sex differences disappeared after adjustment at both 1 year (RR 1.08 95%CI 0.98-1.18) and 5-years post stroke (RR 1.08 95% CI 0.97-1.20). The key contributors to worse outcomes in women were greater age, pre-stroke dependency, severe strokes and atrial fibrillation (AF, mortality only) compared with men. Conc

An approach to acid rock drainage source term modelling involving sources (waste rock piles, open pits and underground mines) and receptors (streams and lakes) is presented. The method involves a mass source term for numerous advective particle paths with computed travel times from source to receptor using groundwater flow modelling software. The result is a temporal mass loading function for each receptor. A case history of a mine containing acid-generating rock, deposited in subaerial waste rock piles and used as subaqueous backfill in open pits, is discussed. The results illustrate the flexibility and utility of the source-term/particle path modelling approach for estimating mass loads to surface water receptors. The use of high vertical resolution 3D models is critical to the successful estimation of flows between sources and receptors. The computational effort required is much less than for a conventional transport simulation., An approach to acid rock drainage source term modelling involving sources (waste rock piles, open pits and underground mines) and receptors (streams and lakes) is presented. The method involves a mass source term for numerous advective particle paths with computed travel times from source to receptor using groundwater flow modelling software. The result is a temporal mass loading function for each receptor. A case history of a mine containing acid-generating rock, deposited in subaerial waste rock piles and used as subaqueous backfill in open pits, is discussed. The results illustrate the flexibility and utility of the source-term/particle path modelling approach for estimating mass loads to surface water receptors. The use of high vertical resolution 3D models is critical to the successful estimation of flows between sources and receptors. The computational effort required is much less than for a conventional transport simulation.

Importance: The underenrollment of women in randomized clinical trials represents a threat to the validity of the evidence supporting clinical guidelines and potential disparities in access to novel treatments. Objective(s): To determine whether women were underenrolled in contemporary randomized clinical trials of acute stroke therapies published in 9 major journals after accounting for their representation in underlying stroke populations. Data Sources: MEDLINE was searched for acute stroke therapeutic trials published between January 1, 2010, and June 11, 2020. Study Selection: Eligible articles reported the results of a phase 2 or 3 randomized clinical trial that enrolled patients with stroke and/or transient ischemic attack and examined a therapeutic intervention initiated within 1 month of onset. Data Extraction: Data extraction was performed by 2 independent authors in duplicate. Individual trials were matched to estimates of the proportion of women in underlying stroke populations using the Global Burden of Disease database. Main Outcomes and Measures: The primary outcome was the enrollment disparity difference (EDD), the absolute difference between the proportion of trial participants who were women and the proportion of strokes in the underlying disease populations that occurred in women. Random-effects meta-analyses of the EDD were performed, and multivariable metaregression was used to explore the associations of trial eligibility criteria with disparity estimates. Result(s): The search returned 1529 results, and 115 trials (7.5%) met inclusion criteria. Of 121105 randomized patients for whom sex was reported, 52522 (43.4%) were women. The random-effects summary EDD was -0.053 (95% CI, -0.065 to -0.040), indicating that women were underenrolled by 5.3 percentage points. This disparity persisted across virtually all geographic regions, intervention types, and stroke types, apart from subarachnoid hemorrhage (0.117 [95% CI, 0.084 to 0.150]). When subarachn

Importance: The underenrollment of women in randomized clinical trials represents a threat to the validity of the evidence supporting clinical guidelines and potential disparities in access to novel treatments. Objective(s): To determine whether women were underenrolled in contemporary randomized clinical trials of acute stroke therapies published in 9 major journals after accounting for their representation in underlying stroke populations. Data Sources: MEDLINE was searched for acute stroke therapeutic trials published between January 1, 2010, and June 11, 2020. Study Selection: Eligible articles reported the results of a phase 2 or 3 randomized clinical trial that enrolled patients with stroke and/or transient ischemic attack and examined a therapeutic intervention initiated within 1 month of onset. Data Extraction: Data extraction was performed by 2 independent authors in duplicate. Individual trials were matched to estimates of the proportion of women in underlying stroke populations using the Global Burden of Disease database. Main Outcomes and Measures: The primary outcome was the enrollment disparity difference (EDD), the absolute difference between the proportion of trial participants who were women and the proportion of strokes in the underlying disease populations that occurred in women. Random-effects meta-analyses of the EDD were performed, and multivariable metaregression was used to explore the associations of trial eligibility criteria with disparity estimates. Result(s): The search returned 1529 results, and 115 trials (7.5%) met inclusion criteria. Of 121105 randomized patients for whom sex was reported, 52522 (43.4%) were women. The random-effects summary EDD was -0.053 (95% CI, -0.065 to -0.040), indicating that women were underenrolled by 5.3 percentage points. This disparity persisted across virtually all geographic regions, intervention types, and stroke types, apart from subarachnoid hemorrhage (0.117 [95% CI, 0.084 to 0.150]). When subarachn