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Background: Studies suggest divergent temporal trends in stroke incidence in high income countries, with increasing rates in younger people, particularly women. No age- and sex-specific stroke incidence data are available for Latin American and Caribbean (LAC) regions, despite large populations undergoing rapid structural changes. Aim: To determine temporal trends in age and sex stroke incidence in LAC populations. Methods: A systematic review in accordance with MOOSE and PRISMA guidelines was undertaken with a modified Cochrane Stroke Group search strategy of MEDLINE, WOS, and LILACS databases, to identify relevant references for prospective observational studies with sex-disaggregated data on stroke incidence in LAC populations from January 1997 to December 2021. Two independent reviewers screened titles/abstracts, and reviewed selected full text articles. Random-effects meta-analysis was conducted to estimate the pooled overall crude stroke incidence and relative temporal rate ratio (RTTR) by age-groups in all and sex-disaggregated data. The Joanna Briggs Institute’s risk of bias assessment was applied. Results: Of 9242 identified records, 6 LAC studies (9 periods) were selected. Overall crude stroke incidence was higher in men than women (incidence [men:women] rate ratio [IRR] = 1.12, 95% confidence interval [CI] 1.04-1.21 [I 2 =38.3%]). When analyzed for temporal trend, relative ratio of stroke incidence was greater in younger than older age-groups ( Conclusions: Divergent temporal trends in stroke incidence are apparent in LAC, with less favorable trends in younger age-groups and especially in young women. Further studies are needed to understand these findings and establish strategies targeting prevention in younger populations.

Background and Aims: OPTIMISTmain is an international, multicenter, stepped-wedge cluster randomized trial to determine effectiveness and safety of less-intensive versus standard monitoring in thrombolysis-treated patients with mild-moderate acute ischemic stroke. A process evaluation was undertaken to determine feasibility, acceptability, and impact of the intervention on care processes, experience and staffing. Methods: A sample of stroke care nursing managers and unit staff from 7 US sites were invited to participate in semi-structured interviews at an early stage of the study. Implementer clinician surveys were undertaken pre- and post-intervention to define integration of the intervention. Qualitative data were independently analyzed by 2 coders; survey data reported from descriptive analysis. Results: 19 nurses were interviewed from the units with 1:2 to 1:6 nurse-to-patient ratios. Less-intensive monitoring was well accepted: less time constraints and improved workload, and perceived to be cost efficient from improved use of neuro-intensive care beds. Some nurses had initial safety concerns over missing deteriorating patients. Less-intensive monitoring led to patients being less irritable and more cooperative from having more rest. There was greater flexibility in the allocation of nursing staff from workforce shortages arising due to the COVID pandemic. Similar results were evident in the survey (13 hospitals, 34 respondents): 80% of respondents agreed that less-intensive monitoring benefited work; 74% believed it should be widely adopted at a national level. Nurses reported time being freed up to provide more patient education (56%), continence/daily living care (50%), early mobilization (26%), mood/cognition assessment (44%), and other aspects (24%, e.g. communication, family support). Conclusions: Less-intensive monitoring after thrombolysis for acute ischemic stroke patients appears feasible and acceptable among US healthcare professionals.

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921.

Background and Purpose: A comprehensive understanding of the long-term impact of stroke assists in health care planning. We aimed to determine changes in rates, causes, and associated factors for hospital presentations among long-term survivors of stroke. Methods: Person-level data from the AuSCR (Australian Stroke Clinical Registry) during 2009 to 2013 were linked with state-based health department emergency department and hospital admission data. The study cohort included adults with first-ever stroke who survived the first 6 months after discharge from hospital. Annualized rates of hospital presentations (nonadmitted emergency department or admission)/person/year were calculated for 1 to 12 months prior, and 7 to 12 months (inclusive) after hospitalization. Multilevel, negative binomial regression was used to identify associated factors after adjustment for prestroke hospital presentations and stratification for perceived impairment status. Perceived impairments to health were defined according to the subscales and visual analog health status scores on the 5-Dimension European Quality of Life Scale. Results: There were 7183 adults with acute stroke, 7-month survivors (median age 72 years; 56% male; 81% ischemic, and 42% with impairment at 90–180 days) from 39 hospitals included in this landmark analysis. Annualized presentations/person increased from 0.88 (95% CI, 0.86–0.91) to 1.25 (95% CI, 1.22–1.29) between the prestroke and poststroke periods, with greater rate increases in those with than without perceived impairment (55% versus 26%). Higher presentation rates were most strongly associated with older age (≥85 versus 65 years, incidence rate ratio, 1.52 [95% CI, 1.27–1.82]) and greater comorbidity score (incidence rate ratio, 1.06 [95% CI, 1.02–1.10]), whereas reduced rates were associated with greater social advantage (incidence rate ratio, 0.71 [95% CI, 0.60–0.84]). Poststroke hospital presentations (7–12 months) were most frequently related to recurrent cardiovascular and cerebrovascular events and sequelae of stroke. Conclusions: A large increase in annualized hospital presentation rates after stroke indicates the potential for improved community management and support for this vulnerable patient group.

Background and Purpose— Patient-centered outcomes are important. We aimed to determine predictors of health-related quality of life (HRQoL) and develop utility-weighted modified Rankin Scale (mRS) scores in thrombolyzed acute ischemic stroke patients from both arms of ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods— ENCHANTED was an international quasi-factorial clinical trial of different doses of intravenous alteplase and intensities of blood pressure control in acute ischemic stroke patients, with outcomes on the 5-Dimensional European Quality of Life Scale and mRS assessed at 90 days post-randomization. Logistic regression models were used to identify baseline predictors of poor HRQoL (≤mean 5-Dimensional European Quality of Life Scale utility scores). Ordinary least squares regression derived utility-weighted mRS scores. Results— In 4016 acute ischemic stroke patients with complete 5-Dimensional European Quality of Life Scale and mRS data, independent predictors of poor HRQoL were older age (odds ratio, 1.19 [95% CI, 1.12–1.27], per 10-year increase), non-Asian ethnicity (1.91 [1.61–2.27]), greater stroke severity on the National Institutes of Health Stroke Scale (1.11 [1.09–1.12]), diabetes mellitus (1.41 [1.18–1.69]), premorbid disability (mRS score 1 versus 0; 1.62 [1.33–1.97]), large vessel atheromatous pathogenesis (1.32 [1.12–1.54]), and proxy respondent (2.35 [2.01–2.74]). Sensitivity analyses indicate the ethnicity influence on HRQoL was driven by the high proportion of Chinese (62.9% of Asian) participants with better HRQoL compared with non-Chinese or other Asian groups. Derived utility values across mRS scores 0 to 5 were 0.977, 0.885, 0.748, 0.576, 0.194, and −0.174, respectively. Correlations between mRS and 5-Dimensional European Quality of Life Scale scores were stronger in Asians. Conclusions— HRQoL is worse after thrombolyzed acute ischemic stroke in the elderly, non-Asians, with greater initial severity, diabetes mellitus, premorbid disability, due to large vessel atheroma, and proxy assessment. The broader significance of better HRQoL in Asians is tempered by Chinese participants dominating analyses. From utility-weighted mRS scores indicating the greatest steps in mRS scores are between 5 and 3, treatments to avoid major disability provide the greatest benefits for patients. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Background and Purpose: Although a target of 80% medication adherence is commonly cited, it is unclear whether greater adherence improves survival after stroke or transient ischemic attack (TIA). We investigated associations between medication adherence during the first year postdischarge, and mortality up to 3 years, to provide evidence-based targets for medication adherence. Methods: Retrospective cohort study of 1-year survivors of first-ever stroke or TIA, aged ≥18 years, from the Australian Stroke Clinical Registry (July 2010–June 2014) linked with nationwide prescription refill and mortality data (until August 2017). Adherence to antihypertensive agents, statins, and nonaspirin antithrombotic medications was based on the proportion of days covered from discharge until 1 year. Cox regression with restricted cubic splines was used to investigate nonlinear relationships between medication adherence and all-cause mortality (to 3 years postdischarge). Models were adjusted for age, sex, socioeconomic position, stroke factors, primary care factors, and concomitant medication use. Results: Among 8363 one-year survivors of first-ever stroke or TIA (44% aged ≥75 years, 44% female, 18% TIA), 75% were supplied antihypertensive agents. In patients without intracerebral hemorrhage (N=7446), 84% were supplied statins, and 65% were supplied nonaspirin antithrombotic medications. Median adherence was ≈90% for each medication group. Between 1% and 100% adherence, greater adherence to statins or antihypertensive agents, but not nonaspirin antithrombotic agents, was associated with improved survival. When restricted to linear regions above 60% adherence, each 10% increase in adherence was associated with a reduction in all-cause mortality of 13% for antihypertensive agents (hazard ratio, 0.87 [95% CI, 0.81–0.95]), 13% for statins (hazard ratio, 0.87 [95% CI, 0.80–0.95]), and 15% for nonaspirin antithrombotic agents (hazard ratio, 0.85 [95% CI, 0.79–0.93]). Conclusions: Greater levels of medication adherence after stroke or TIA are associated with improved survival, even among patients with near-perfect adherence. Interventions to improve medication adherence are needed to maximize survival poststroke.

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 difference unadjusted 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.

Background and Purpose— Stroke disability is a major health burden in rural China where rehabilitation services are inadequate. We aimed to determine the effectiveness of a novel nurse-led, caregiver-delivered model of stroke rehabilitation in rural China. Methods— A multicenter prospective, randomized open, blinded outcome assessed, controlled trial was conducted in 3 rural county hospitals in China: Zhangwu, Liaoning Province (Northeast); Qingtongxia, Ningxia Hui Autonomous Region (Northwest); and Dianjiang, Chongqing Municipality (Southwest). Adult patients (age 18–79 years) with residual disability (Barthel Index score ≤80/100) after a recent acute stroke were randomized to a new service model or usual care. The new intervention was multifaceted and was based on a task-shifting / training-the-trainers model, supported by a custom-designed smartphone application, where patients and caregivers received evidence-based in-hospital education and stroke rehabilitation training (focus on mobility, self-care, and toileting), delivered by trained nurses before hospital discharge, and 3 postdischarge support telephone calls. Outcome assessments were undertaken before hospital discharge and at 3 and 6 months. Primary outcome was physical functioning (Barthel Index scores) at 6 months, assessed by research staff blind to treatment allocation, adjusted for baseline covariates in an intention-to-treat analysis. Secondary outcomes included measures of mobility, health-related quality of life, mood, and caregiver burden. The study included a process evaluation that assessed intervention fidelity. Results— From November 2014 to December 2016, 246 stroke patients were randomized to intervention (n=118) or control (n=128) groups. There was no statistically significant difference in adjusted 6-month Barthel Index scores between groups (70.1 versus 74.1, mean difference, −4.0 [95% CI, −10.0 to 2.9]), nor any differences across the other outcome measures. Process evaluation interviews revealed that the intervention was desirable and positively accepted by nurses, caregivers, and patients but was considered too complex despite efforts to simplify materials for the rural context. Key strategies identified for future studies included the use of community health workers, smartphone application enhancement, and simpler and more frequent training for nurses, caregivers, and patients. Conclusions— A novel nurse-led, digital supported, caregiver-delivered stroke rehabilitation program did not improve patient physical functioning after stroke in rural China. Further stroke rehabilitation research suitable for resource-poor settings is required, with several components being suggested through stakeholder interviews in our study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT02247921.

Background and Purpose— We investigated factors associated with early and delayed neurological deterioration (END and DND, respectively) after acute spontaneous intracerebral hemorrhage in the main INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial)-2. Methods— INTERACT-2 was a randomized trial of early intensive versus guideline-recommended blood pressure lowering in hypertensive intracerebral hemorrhage ( Results— Of 2598 participants, 450 (17.3%) had either END or DND. Non-China recruitment, higher systolic blood pressure, larger baseline hematoma volume, left hemisphere hematoma location, intraventricular hemorrhage, subarachnoid extension, heterogeneous hematoma density, and cerebral white matter lesions, were predictors of END (all P ≤0.045). Higher systolic blood pressure, lower diastolic blood pressure, higher glucose, larger baseline hematoma volume, intraventricular hemorrhage, lobar location, brain atrophy, and heterogeneous hematoma density were predictors of DND (all P ≤0.042). END and DND were both related to death, and death or major disability (modified Rankin Scale scores of 3–6), in adjusted analyses ( P Conclusions— Common variables, most directly related to the intracerebral hemorrhage morphology and underlying cerebral features, determine END and DND and their influence on poor outcomes of death and major disability. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Supplemental Digital Content is available in the text., Background and Purpose— Hospital uptake of evidence-based stroke care is variable. We aimed to determine the impact of a multicomponent program involving financial incentives and quality improvement interventions, on stroke care processes. Methods— A prospective study of interventions to improve clinical care quality indicators at 19 hospitals in Queensland, Australia, during 2010 to 2015, compared with historical controls and 23 other Australian hospitals. After baseline routine audit and feedback (control phase, 30 months), interventions involving financial incentives (21 months) and then addition of externally facilitated quality improvement workshops with action plan development (9 months) were implemented. Postintervention phase was 13 months. Data were obtained for the analysis from a previous continuous audit in Queensland and subsequently the Australian Stroke Clinical Registry. Primary outcome: change in median composite score for adherence to ≤8 indicators. Secondary outcomes: change in adherence to self-selected indicators addressed in action plans and 4 national indicators compared with other Australian hospitals. Multivariable analyses with adjustment for clustered data. Results— There were 17 502 patients from the intervention sites (median age, 74 years; 46% women) and 20 484 patients from other Australian hospitals. Patient characteristics were similar between groups. There was an 18% improvement in the primary outcome across the study periods (95% CI, 12%–24%). The largest improvement was following introduction of financial incentives (14%; 95% CI, 8%–20%), while indicators addressed in action plans provided an 8% improvement (95% CI, 1%–17%). The national score (4 indicators) improved by 17% (95% CI, 13%–20%) versus 0% change in other Australian hospitals (95% CI, −0.03 to 0.03). Access to stroke units improved more in Queensland than in other Australian hospitals (P

Objective: To identify any differential efficacy and safety of low- versus standard-dose intravenous alteplase for lacunar versus non-lacunar acute ischemic stroke (AIS) in the alteplase dose-arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: In a cohort of 3297 ENCHANTED participants, we identified those with lacunar or non-lacunar AIS with different levels of confidence (definite/probable/possible) according to pre-specified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration [END] or death) and treatment effects of low- versus standard-dose alteplase across lacunar and non-lacunar AIS with adjustment for baseline covariables. Results: Of 2588 participants with available imaging and clinical data, we classified cases as definite or probable lacunar (n=490) or non-lacunar AIS (n=2098) for primary analyses. Regardless of the alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% CI] 0.60 [0.47-0.77]) and other clinical or safety outcomes, compared to participants with non-lacunar AIS. Overall, low-dose alteplase (compared to standard) had no differential effect on the functional outcome (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of ICH. There were no differential treatment effects of low- versus standard-dose alteplase on all outcomes across lacunar and non-lacunar AIS (all P interaction ≥0.07). Conclusions: We found no clear evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard-dose for definite/probable lacunar AIS.

Background and Purpose: We determined associations of physiological abnormalities (systolic blood pressure, glucose, and body temperature) and warfarin use with outcomes in spontaneous intracerebral hemorrhage. Methods: Post hoc analyses of INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial) comparing systolic blood pressure control (6.5 mmol/L), body temperature (≤37.5 °C versus >37.5 °C), and warfarin use (no versus yes) and death or major disability (modified Rankin Scale scores 3–6 at 90 days). Results: Baseline score distribution was 0 (7.7%), 1 (15.6%), 2 (19.0%), 3 (19.1%), 4 (15.2%), 5 (11.6%), 6 (8.9%), and 7 (2.9%). After adjustment for baseline neurological severity and potential confounders, significant linear associations were evident for increasing (per point) score and death or major disability (odds ratio, 1.12 [95% CI, 1.07–1.17]), death (odds ratio, 1.15 [95% CI, 1.07–1.23]), and major disability (odds ratio, 1.10 [95% CI, 1.05–1.15]). Conclusions: Combination of abnormal physiological parameters and warfarin use is associated with poor outcomes in intracerebral hemorrhage. Effects of their early control is under investigation in INTERACT3 (Intensive Care Bundle With Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial). Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Background and Purpose: To determine factors associated with fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on magnetic resonance imaging and their prognostic significance in thrombolysis-treated patients with acute ischemic stroke from the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) trial alteplase-dose arm. Methods: Patients with acute ischemic stroke (N=293) with brain magnetic resonance imaging (FLAIR and diffusion-weighted imaging sequences) scanned Results: Prior atrial fibrillation, LVO, large infarct volume, and anterior circulation infarction were independently associated with FLAIR-HAs. The rate of modified Rankin Scale scores 0 to 1 was numerically lower in patients with FLAIR-HAs versus without (69/152 [45.4%] versus 75/131 [57.3%]), as was the subset of LVO (37/93 [39.8%] versus 9/16 [56.3%]), but not in those without LVO (25/36 [69.4%] versus 60/106 [56.6%]). After adjustment for covariables, FLAIR-HAs were independently associated with increased primary outcome (adjusted odds ratio [95% CI]: overall 4.14 [1.63–10.50]; with LVO 4.92 [0.87–27.86]; no LVO 6.16 [1.57–24.14]) despite an increased risk of hemorrhagic infarct (4.77 [1.12–20.26]). Conclusions: FLAIR-HAs are more frequent in acute ischemic stroke with cardioembolic features and indicate potential for a favorable prognosis in thrombolysis-treated patients possibly mediated by LVO. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Background and Purpose— Early presentation is critical for receiving effective reperfusion therapy for acute ischemic stroke, therefore, we undertook a national survey of awareness and responses to acute stroke symptoms in China. Methods— We undertook a cross-sectional community-based study of 187 723 adults (age ≥40 years) presenting to 69 administrative areas across China between January 2017 and May 2017 to determine the national stroke recognition rate and the correct action rate. Multivariable logistic regression models were used to identify factors associated with stroke recognition and intention-to-avail emergency medical services. Results— Estimates of stroke recognition rate and correct action rate were 81.9% (153 675/187 723) and 60.9% (114 380/187 723), respectively, but these rates varied widely by sociodemographic status, region, and stroke risk. Approximately one-third of participants who recognized a stroke failed to call emergency medical service. Low likelihood of emergency medical service use was associated with younger age (40–59 years), being male, rural location, (regions of east, south, and northwest China), high body mass index (≥24), low education (primary school or below), low personal income (P Conclusions— Substantial discrepancies exist between stroke recognition and correct action and not all stroke patients know the appropriate responses. Further, national stroke educational programs with specific plans targeting different groups are needed, which do not solely focus on stroke recognition, but also on the appropriate responses at the time of a stroke.

Purpose: We aimed to determine differences in demographics, management and outcomes between Asian and non-Asian participants with acute ischemic stroke (AIS) in the Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED). Methods: ENCHANTED was a partial-factorial trial in thrombolysis-eligible AIS patients randomly assigned to: (i) low-dose (0.6mg/kg) or standard-dose (0.9mg/kg) alteplase and; (ii) intensive (target systolic blood pressure [SBP] 130-140 mmHg) or guideline-recommended Results: Among 4562 patients (mean age 66.6 years, 37.8% female, 65.5% Asian) Asian patients were younger and less likely to have atrial fibrillation and hypercholesterolemia and taking fewer antihypertensive, warfarin, aspirin and statin therapy compared to non-Asians. They were also less likely to receive thromboembolic prophylaxis, be admitted to an acute stroke unit, be mobilized by therapist, and receive any rehabilitation over the first 7 days. Despite Asian patients having an increased risk of ICH (adjusted odds ratio 1.48, 95% confidence interval 1.22-1.8; P=0.0001), there were no significant differences compared to non-Asians for overall functional outcomes after adjustment for baseline imbalances. However, Asians had greater disability (1.48, 1.19-1.85; P=0.0005) but less deaths (0.38, 0.27-0.55; P Conclusions: Compared to non-Asians, Asian patients were at increased risk of ICH and residual disability after thrombolysis treatment for AIS, suggesting the need to access more evidence-based care in acute management.

Background and Aims: Epidemiological studies show significant variations in hypertension management within and between countries. The level of regional variation in early blood pressure (BP) management after acute stroke is uncertain. Methods: Data are from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED), a partial-factorial, international randomized controlled trial (RCT) of thrombolysis-eligible acute ischemic stroke (AIS) patients with systolic BP (SBP >150 mmHg) assigned to intensive (target SBP 130-140 mmHg) vs. guideline-recommended (SBP Results: There were 2196 AIS (38% women, mean age 67[12] years) and 2829 acute ICH (37% women, mean age 63[13] years) patients in these analyzes. Commonly used intravenous BP lowering agents are labetalol, nitroglycerin, and topical Nitrates in western countries; mannitol, urapidil, and sodium nitroprusside in China; nicardipine in other Asian countries; and sodium nitroprusside and labetalol in South America. Western patients were more likely to receive BP lowering treatment in the first 24 hours and treated with multiple agents, and had larger magnitude of SBP reduction and greater SBP variability. BP control parameters over 2-7 days were comparable between regions. Conclusion: Regional variations in early BP management in acute stroke translated into differences in magnitude of SBP reduction and SBP variability in patients.

Background and Purpose— Infratentorial intracerebral hemorrhage (ICH) has a poor outcome but is rarely analyzed by cerebellar versus brain stem location. We evaluated this relationship and clinical outcomes among participants of the INTERACT 1 and 2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials). Methods— Participants with brain stem and cerebellar ICH were compared. Logistic regression models were used to compare outcomes of death or major disability and quality of life. Results— Of 195 included patients, 92 (47%) and 103 (53%) had brain stem and cerebellar ICH, respectively. Patients with brain stem ICH were younger (mean [SD] age, 59±13 versus 70±11 years), less female (28.3% versus 50.5%), with higher admission National Institutes of Health Stroke Scale scores (median [interquartile range], 6 [4–10) versus 3 [2–8]), less prior ICH (3% versus 17%), smaller ICH volumes (1.6 mL [1.0–2.8 mL] versus 5.1 mL [2.6–10.7 mL]), and less intraventricular extension (3% versus 39%) than those with cerebellar ICH. Brain stem ICH had higher mortality (odds ratio, 37.1; 95% CI, 1.99–692.27) and worse scores in the European Quality of Life Scale (EQ-5D) pain domain (odds ratio, 3.36; 95% CI, 1.38–8.20). Conclusions— Cerebellar and brain stem ICH differ in their clinical characteristics and prognosis, with the latter being associated with higher case fatality and worse EQ-5D scores in the pain domain. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00226096 and NCT00716079.

A 55-year-old man presents within 2 hours of acute left-sided weakness. Head computed tomography reveals a 60 mL right thalamic hemorrhage. Blood pressure (BP) on presentation is 150/95 mm Hg. Should BP be lowered? If yes, what is the target BP and which antihypertensive agents should be used? Intensive BP Lowering in Intracerebral Hemorrhage ### Craig Anderson As the on-call stroke neurologist, I would treat this patient according to an approved management of intracerebral hemorrhage (ICH) protocol readily available on the hospital intranet and my decision support tool. The patient is at high risk for poor outcome—early presentation, large hematoma, deep location—and early, rapid and sustained control of elevated systolic BP (SBP, target

Background and Purpose— Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods— Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2–6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria. Results— There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81–1.26; P =0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75–1.20; P =0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87–1.21; P =0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00–3.30; P =0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant ( P -trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2–6; OR, 0.84; 95% CI, 0.62–1.12 versus OR, 1.16; 95% CI, 0.99–1.36). Conclusions— Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Background and Purpose— Despite evidence to support the prescription of antihypertensive medications before hospital discharge to promote medication adherence and prevent recurrent events, many patients with stroke miss out on these medications at discharge. We aimed to examine patient, clinical, and system-level differences in the prescription of antihypertensive medications at hospital discharge after stroke. Methods— Adults with acute ischemic stroke or intracerebral hemorrhage alive at discharge were included (years 2009–2013) from 39 hospitals participating in the Australian Stroke Clinical Registry. Patient comorbidities were identified using the International Statistical Classification of Diseases and Related Health Problems (Tenth Edition, Australian Modification ) codes from the hospital admissions and emergency presentation data. The outcome variable and other system factors were derived from the Australian Stroke Clinical Registry dataset. Multivariable, multilevel logistic regression was used to examine factors associated with the prescription of antihypertensive medications at hospital discharge. Results— Of the 10 315 patients included, 79.0% (intracerebral hemorrhage, 74.1%; acute ischemic stroke, 79.8%) were prescribed antihypertensive medications at discharge. Prescription varied between hospital sites, with 6 sites >2 SDs below the national average for provision of antihypertensives at discharge. Prescription was also independently associated with patient and clinical factors including history of hypertension, diabetes mellitus, management in an acute stroke unit, and discharge to rehabilitation. In patients with acute ischemic stroke, females (odds ratio, 0.85; 95% CI, 0.76–0.94), those who had greater stroke severity (odds ratio, 0.81; 95% CI 0.72–0.92), or dementia (odds ratio, 0.65; 95% CI, 0.52–0.81) were less likely to be prescribed. Conclusions— Prescription of antihypertensive medications poststroke varies between hospitals and according to patient factors including age, sex, stroke severity, and comorbidity profile. Implementation of targeted quality improvement initiatives at local hospitals may help to reduce the variation in prescription observed.

Background and Purpose- We investigated factors associated with early and delayed neurological deterioration (END and DND, respectively) after acute spontaneous intracerebral hemorrhage in the main INTERACT (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial)-2. Methods- INTERACT-2 was a randomized trial of early intensive versus guideline-recommended blood pressure lowering in hypertensive intracerebral hemorrhage (6 hours from symptom onset) patients. END and DND were defined as a ≥4-point increase on the National Institutes of Health Stroke Scale or ≥2-point decrease on Glasgow Coma Scale, in periods baseline to 24 hours and 24 hours to 7 days, respectively. Multivariable logistic regression models were used to determine independent predictors of END and DND and 90-day outcomes (death and dependency on the modified Rankin Scale). Results- Of 2598 participants, 450 (17.3%) had either END or DND. Non-China recruitment, higher systolic blood pressure, larger baseline hematoma volume, left hemisphere hematoma location, intraventricular hemorrhage, subarachnoid extension, heterogeneous hematoma density, and cerebral white matter lesions, were predictors of END (all P≤0.045). Higher systolic blood pressure, lower diastolic blood pressure, higher glucose, larger baseline hematoma volume, intraventricular hemorrhage, lobar location, brain atrophy, and heterogeneous hematoma density were predictors of DND (all P≤0.042). END and DND were both related to death, and death or major disability (modified Rankin Scale scores of 3-6), in adjusted analyses ( P0.001). Conclusions- Common variables, most directly related to the intracerebral hemorrhage morphology and underlying cerebral features, determine END and DND and their influence on poor outcomes of death and major disability. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Background and Purpose- Infratentorial intracerebral hemorrhage (ICH) has a poor outcome but is rarely analyzed by cerebellar versus brain stem location. We evaluated this relationship and clinical outcomes among participants of the INTERACT 1 and 2 (Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials). Methods- Participants with brain stem and cerebellar ICH were compared. Logistic regression models were used to compare outcomes of death or major disability and quality of life. Results- Of 195 included patients, 92 (47%) and 103 (53%) had brain stem and cerebellar ICH, respectively. Patients with brain stem ICH were younger (mean [SD] age, 59±13 versus 70±11 years), less female (28.3% versus 50.5%), with higher admission National Institutes of Health Stroke Scale scores (median [interquartile range], 6 [4-10) versus 3 [2-8]), less prior ICH (3% versus 17%), smaller ICH volumes (1.6 mL [1.0-2.8 mL] versus 5.1 mL [2.6-10.7 mL]), and less intraventricular extension (3% versus 39%) than those with cerebellar ICH. Brain stem ICH had higher mortality (odds ratio, 37.1; 95% CI, 1.99-692.27) and worse scores in the European Quality of Life Scale (EQ-5D) pain domain (odds ratio, 3.36; 95% CI, 1.38-8.20). Conclusions- Cerebellar and brain stem ICH differ in their clinical characteristics and prognosis, with the latter being associated with higher case fatality and worse EQ-5D scores in the pain domain. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifiers: NCT00226096 and NCT00716079.

Background: The simplified modified Rankin scale questionnaire (smRSq) was developed to facilitate scoring and precision in assessment of disability outcome on the mRS. We aim to determine the strength of associations between smRSq and mRS among participants of alteplase-dose arm of the ENCHANTED, and also in relation to other stroke outcomes (EQ-5D, NIHSS). Methods: In the ENCHANTED trial, assessments of mRS were made at Days 3, 28 and 90, and smRSq at Days 28 and 90; EQ-5D at Days 28 and 90; NIHSS at 24 and 72 hours. Kappa statistic assessed relationships between smRSq and mRS; and Spearman correlation coefficients of relationship between smRSq and NIHSS and EQ-5D. Results: Of 3010 included patients, good agreement existed between smRSq and mRS (Kw=0.79, 95% CI 0.78-0.81). Moderate correlations between NIHSS and smRSq (r = 0.44, P Conclusions: In a large dataset of a broad range of thrombolysis-eligible patients with acute ischemic stroke, there was a good agreement between smRSq and mRS, and consistence in correlating with other measure of neurological impairment and health-related quality of life. The data confirm the utility of smRSq as a reliable, valid, and simple structured assessment of stroke outcome.

Introduction: Early recurrence of acute ischemic stroke (AIS) predicts adverse outcome, but there is uncertainty about the predictors after intravenous alteplase. We aimed to determine the predictors of stroke/transient ischemic attack (TIA) and their prognostic significance among ENCHANTED participants. Methods: ENCHANTED was an international, randomized, open-label, blinded-endpoint trial of low- versus standard-dose intravenous alteplase in AIS patients. Log-rank test and multivariable analysis with cox-regression models were used to assess the association of baseline characteristics and stroke/TIA recurrence and of functional outcome (modified Rankin scale [mRS] scores 2-6) at 90 days. Results: Among 3297 AIS participants, 103 (3%) had early recurrent AIS/TIA, which was predicted by recruitment in South America (hazard ratio 1.75, 95%CI 1.04-2.94), history of coronary artery disease (1.67, 1.03-2.72) and extra/intra-cranial vessel stenosis (2.94, 1.49-5.81), premorbid mRS ≥1 (1.63, 1.04-2.55), lipid lowering therapy (1.66, 1.03-2.67), multiple ischemic brain imaging lesions (2.33, 1.50-3.61), and cardioembolic stroke (1.58, 1.02-2.46). Early recurrence was independently associated with poor functional outcome (odds ratio 4.76, 95%CI 2.63-8.42). Conclusions: After treatment with intravenous alteplase, early recurrence of cerebral ischemic events complicates recovery and residual disability. Better targeting of preventive strategies in those at high risk, specifically those with cardioatherosclerosis and cardioembolic disease, may improve outcome from AIS.

Introduction: Hospital arrival via ambulance may influence treatment options and outcomes of acute stroke. A national study for Australia has not previously been reported, and inclusion of long-term outcomes is rare. We aimed to determine differences in the characteristics of patients and their outcomes by route of hospital presentation. Methods: Patient-level data linkage of Australian Stroke Clinical Registry (AuSCR) patients with first-ever strokes between January 2010 and December 2013 (n=40 hospitals) were merged with emergency and hospital admissions, and death records. Multilevel regression models were used to determine associations with hospital care and outcome by type of transport to hospital. Results: Among 9315 patients with first-ever stroke, 5601 (60%) arrived by ambulance (52% male; 79% ischemic). Compared to patients arriving by private transport, those arriving by ambulance were older (ambulance, median 77 vs. private, 72 years; P Conclusion: Patients with first-ever stroke who take private transport to hospital experience treatment disadvantages but not worse outcomes. Public education on calling an ambulance for stroke symptoms remains important.

Introduction: Uncertainty persists over the optimal management of blood pressure (BP) in the early phase of acute ischemic stroke (AIS). This study aims to determine the safety and effects of intensive BP lowering on cerebral blood flow and functional outcomes in AIS patients treated with intravenous thrombolysis. Methods: In a randomized controlled trial, AIS patients with a systolic BP of 160-180mmHg were randomized to early intensive BP lowering (systolic target range 140-160mmHg) or guideline-based BP management (systolic range 160-180mmHg) during first 72-hours using primarily intravenous labetalol. All study subjects underwent CT perfusion at baseline, 24 and 72-hours post-randomization to evaluate change in cerebral hemodynamics. Clinical outcome was assessed using a dichotomized modified Rankin scale (scores 0-1 as excellent outcome versus scores 2-6 as poor outcome) at 90 days. Results: Of the 48 recruited patients, 25 (52%) were assigned to the early intensive BP lowering arm and 23 (48%) to the guideline-based BP management arm. Excellent functional outcome at 90 days were similar in the 2 arms- 56% in the early intensive BP lowering arm and 61% in the standard therapy arm. There were no significant differences in the baseline, 24 and 72-hour CT perfusion cerebral hemodynamic parameters or symptomatic intracranial hemorrhage between the 2 study arms. Conclusions: In the early phase of AIS, intensive BP lowering appears to be a safe strategy. Large randomized controlled trials are needed to confirm our study findings.

Background and Purpose: Patient beliefs/values over illness/wellbeing are important considerations in health care delivery. We aimed to map function with health-related quality of life (HRQoL) to derive utility-weighted outcomes to test the efficacy of acute stroke trial interventions. Methods: Physical function and HRQoL were defined by modified Rankin scale (mRS) and EuroQol 5-dimensional questionnaire (EQ-5D) scores, respectively, for calculating utility-weighted mRS (UW-mRS) scores in pooled data from 5 international trials and externally validated in another trial database. UW-mRS was derived using ordinary least squares regression with mRS as a discrete ordinal explanatory dummy variable and EQ-5D as a continuous response variable. Linear regression was used to assess mean UW-mRS scores between intervention groups. Results: UW-mRS scores derived from 19338 acute stroke patients were 0.96, 0.92, 0.75, 0.58, 0.32, -0.093 for mRS scores 0, 1, 2, 3, 4 and 5, respectively. Both UW-mRS and ordinal mRS were statistically significant in INTERACT (P=0.04 and P=0.02 for UW-mRS and ordinal mRS, respectively) and ENCHANTED (0.04, P Conclusions: UW-mRS as an outcome measure provides comparable statistical efficiency to ordinal analysis of mRS, but may better reflect patient and societal views on recovery. Greater HRQoL occurs where there is a large favourable shift away from high disability (mRS scores 3-5); interventions that achieve this provide the greatest benefit to patients.

Background and Purpose— The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure–lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods— We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography ( Results— WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02–1.98), 1.47 (1.08–1.99), and 1.64 (1.21–2.22), respectively (all P for trend Conclusions— Preexisting cerebral SVD manifestations of WML and brain atrophy predict poor outcome in acute intracerebral hemorrhage. There is no apparent hazard of early intensive lowering of blood pressure according to the INTERACT2 protocol, in patients with underlying cerebral SVD. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Introduction: Women appear to experience worse HRQoL after stroke than men. However, women without stroke also report poorer health status than men in all ages. Therefore, it is uncertain whether the sex disparity in HRQoL is caused by stroke or other differences between men and women. Methods: First-ever strokes admitted to 39 hospitals participating in AuSCR from 2010-2014, had HRQoL assessed at 3-6 months after stroke using EQ-5D-3L and results transformed into utility values for the respondents and among those who died, ranging from -0.516 (worse than death), 0 (death) to 1 (perfect health). Calculated mean EQ5D utility scores for stroke registrants were then stratified by age ( Results: After a median follow-up of 139 days, there were 2700 deaths out of 14118 registered cases of stroke. About 60% (6852/11418) of survivors after stroke completed follow-up surveys with EQ5D assessment; 44% being female. In the stroke group, only women aged > 65 years old had significantly lower utility scores than the elderly men of the same age. After standardisation for age, weighted MDs between those with and without stroke were slightly greater for women (MD 0.40 95% CI 0.37, 0.42) compared to men (MD 0.36 95% CI 0.34, 0.38. However, the sex difference in weighted utility scores between those with and without stroke (MD 0.04) was below the clinically meaningful threshold. Conclusion: Stroke causes substantial loss of HRQoL in both men and women especially with increasing age. However, the differences in utility scores between those men and women with and without stroke were not clinically relevant. Future studies of sex differences in HRQoL after stroke should consider the innate differences in HRQoL between men and women when reporting results.

Background and Purpose— Mannitol is often used to reduce cerebral edema in acute intracerebral hemorrhage but without strong supporting evidence of benefit. We aimed to determine the impact of mannitol on outcome among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). Methods— INTERACT2 was an international, open, blinded end point, randomized controlled trial of 2839 patients with spontaneous intracerebral hemorrhage ( Results— There was no significant difference in poor outcome between mannitol (n=1533) and nonmannitol (n=993) groups: propensity score–matched odds ratio of 0.90 (95% confidence interval, 0.75–1.09; P =0.30) and multivariable odds ratio of 0.87 (95% confidence interval, 0.71–1.07; P =0.18). Although a better outcome was suggested in patients with larger (≥15 mL) than those with smaller (P homogeneity Conclusions— Mannitol seems safe but might not improve outcome in patients with acute intracerebral hemorrhage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Purpose— The aim of this guideline is to present current and comprehensive recommendations for the diagnosis and treatment of spontaneous intracerebral hemorrhage. Methods— A formal literature search of PubMed was performed through the end of August 2013. The writing committee met by teleconference to discuss narrative text and recommendations. Recommendations follow the American Heart Association/American Stroke Association methods of classifying the level of certainty of the treatment effect and the class of evidence. Prerelease review of the draft guideline was performed by 6 expert peer reviewers and by the members of the Stroke Council Scientific Oversight Committee and Stroke Council Leadership Committee. Results— Evidence-based guidelines are presented for the care of patients with acute intracerebral hemorrhage. Topics focused on diagnosis, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, outcome prediction, rehabilitation, secondary prevention, and future considerations. Results of new phase 3 trials were incorporated. Conclusions— Intracerebral hemorrhage remains a serious condition for which early aggressive care is warranted. These guidelines provide a framework for goal-directed treatment of the patient with intracerebral hemorrhage.

Background and Purpose— We developed and validated a simple algorithm to predict the risk of hematoma growth in acute spontaneous intracerebral hemorrhage (ICH) to better inform clinicians and researchers in their efforts to improve outcomes for patients. Methods— We analyzed data from the computed tomography substudies of the pilot and main phases of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trials (INTERACT1 and 2, respectively). The study group was divided into a derivation cohort (INTERACT2, n=964) and a validation cohort (INTERACT1, n=346). Multivariable logistic regression was used to identify factors associated with clinically significant (≥6 mL) increase in hematoma volume at 24 hours after symptom onset. A parsimonious risk score was developed on the basis of regression coefficients derived from the logistic model. Results— A 24-point BRAIN score was derived from INTERACT2 (C-statistic, 0.73) based on baseline ICH volume (mL per score, ≤10=0, 10–20=5, >20=7), recurrent ICH (yes=4), anticoagulation with warfarin at symptom onset (yes=6), intraventricular extension (yes=2), and number of hours to baseline computed tomography from symptom onset (≤1=5, 1–2=4, 2–3=3, 3–4=2, 4–5=1, >5=0) predicted the probability of ICH growth (ranging from 3.4% for 0 point to 85.8% for 24 points) with good discrimination (C-statistic, 0.73) and calibration (Hosmer–Lemeshow P =0.82) in INTERACT1. Conclusions— The simple BRAIN score predicts the probability of hematoma growth in ICH. This could be used to improve risk stratification for research and clinical practice. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00226096 and NCT00716079.

Background and Purpose— Degree and timing of blood pressure (BP) lowering treatment in relation to hematoma growth were investigated in the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial-2 (INTERACT2). Methods— INTERACT2 was an international clinical trial of intensive (target systolic BP [SBP], Results— Greater SBP reduction was associated with reduced hematoma growth (13.3, 5.0, and 3.0 mL for P trend6 hours (5.4 mL). The smallest mean absolute hematoma growth (2.0 mL) was in those achieving target SBP 5 to 8 times versus 3 to 4 (3.1 mL) and 0 to 2 times (5.2 mL). Conclusions— Intensive BP lowering with greater SBP reduction, which is achieved quickly and maintained consistently, seems to provide protection against hematoma growth for 24 hours. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00716079.

Background and Purpose— Clinical utility of electronic Alberta Stroke Program Early CT Score (e-ASPECTS), an automated system for quantifying signs of infarction, was evaluated in a large database of thrombolyzed patients with acute ischemic stroke. Methods— All baseline noncontrast computed tomographic scans of patients with anterior circulation acute ischemic stroke who participated in the alteplase dose arm of the randomized controlled trial ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) were reviewed; poor quality and large (>6 mm) slice thickness were excluded. Included scans had e-ASPECTS scores correlated with baseline neurological severity (National Institutes of Health Stroke Scale scores) and 90-day disability outcomes (modified Rankin Scale scores). Multivariable logistic regression models were used to determine the predictive ability of e-ASPECTS for disability outcomes and symptomatic intracranial hemorrhage. Results— Of 2426 available computed tomographic images, 1480 (61%) were included in analyses of e-ASPECTS scores (median 9 [interquartile range, 8–10], 77% with good [range, 8–10] scores). Lower e-ASPECTS scores (per 1-point decrease) were significantly associated with increasing baseline National Institutes of Health Stroke Scale scores ( r , −0.31; P r , −0.27; P Conclusions— e-ASPECT scores from thin computed tomographic slices (≤6 mm) were highly correlated with baseline neurological severity and independently predict functional recovery and adverse outcomes in acute ischemic stroke. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01422616.

Background and Purpose— Major pathological stroke types (ischemic stroke [IS], primary intracerebral hemorrhage [ICH], and subarachnoid hemorrhage) and IS subtypes, have differing risk factors, management, and prognosis. We report changes in major stroke types and IS subtypes incidence during 10 years using data from the ARCOS (Auckland Regional Community Stroke Study) III performed during 12 months in 2002 to 2003 and the fourth ARCOS study (ARCOS-IV) performed in 2011 to 2012. Methods— ARCOS-III and ARCOS-IV were population-based registers of all new strokes in the greater Auckland region (population aged >15 years, 1 119 192). Strokes were classified into major pathological types (IS, ICH, subarachnoid hemorrhage, and undetermined type). Crude annual age-, sex-, and ethnic-specific stroke incidence with 95% confidence intervals was calculated. ISs were subclassified using TOAST (Trial of ORG 10172 in Acute Stroke Treatment) criteria into 5 etiologic groups. Rate ratios with 95% confidence intervals were calculated for differences in age-standardized rates between the 2 studies. Results— In ARCOS-IV, there were 1329 (81%) ISs, 211 (13%) ICHs, 79 (5%) subarachnoid hemorrhages, and 24 (1%) undetermined type strokes. The proportional distribution of IS subtypes was 29% cardioembolism, 21% small-vessel occlusion, 15% large-artery atherosclerosis, 5% other determined etiology, and 31% undetermined type. Between 2002 and 2011, age-standardized incidence decreased for subarachnoid hemorrhage (rate ratios, 0.73; 95% confidence intervals, 0.54–0.99) and undetermined type (rate ratios, 0.14; 95% confidence intervals, 0.09–0.22). Rates were stable for IS and ICH. Among IS subtypes, large-artery atherosclerosis and small-vessel occlusion rates increased significantly. The frequency of all risk factors increased in IS. Ethnic differences were observed for both stroke subtype rates and their risk factor frequencies. Conclusions— A lack of change in IS and ICH incidence may reflect a trend toward increased incidence of younger strokes. Increased rates of large-artery atherosclerosis and small-vessel occlusion are associated with increased smoking and high blood pressure. Ethnic differences in the proportional distribution of pathological stroke subtypes suggest differential exposure and susceptibility to risk factors.

Background and Purpose— In multicultural Australia, some patients with stroke cannot fully understand, or speak, English. Language barriers may reduce quality of care and consequent outcomes after stroke, yet little has been reported empirically. Methods— An observational study of patients with stroke or transient ischemic attack (2010–2015) captured from 45 hospitals participating in the Australian Stroke Clinical Registry. The use of interpreters in hospitals, which is routinely documented, was used as a proxy for severe language barriers. Health-Related Quality of Life was assessed using the EuroQoL-5 dimension-3 level measured 90 to 180 days after stroke. Logistic regression was undertaken to assess the association between domains of EuroQoL-5 dimension and interpreter status. Results— Among 34 562 registrants, 1461 (4.2%) required an interpreter. Compared with patients without interpreters, patients requiring an interpreter were more often women (53% versus 46%; P P P Conclusions— Patients requiring interpreters reported poorer Health Related Quality of Life after stroke/transient ischemic attack despite greater access to stroke units. These findings should be interpreted with caution because we are unable to account for prestroke Health Related Quality of Life. Further research is needed.

Background and Purpose: There is limited evidence on head positioning in acute ischemic stroke (AIS) or intracerebral hemorrhage (ICH). Potential benefits for lying flat (0°) include improved collateral blood flow in AIS and for head up (30°) reduced cerebral oedema in ICH. The Head Positioning in Stroke Trial (HeadPoST) aims to provide reliable evidence on the optimum head position in acute stroke. Methods: HeadPoST is a prospective, cluster randomised, crossover, blinded outcome assessed, clinical trial with consecutive patient recruitment who were positioned within 24 hours of admission. Hospitals were randomised to service organisation to compare lying flat vs. sitting up (≥30°) head positioning of stroke patients. An innovative centralized remote monitoring system was used to assess data quality across participating countries. Results: Over a 30 month study period, 10,000+ patients were recruited across 114 hospitals in 9 countries. A web-based monitoring system provided alerts for cross-over time points and achievement of cluster balance. Centralised reports included serious adverse events, protocol deviations, forms completion, data queries, entry delays and data validation, which were distributed to regional co-ordinating centres for action. Details of these procedures are outlined. Conclusions: Reliable, complete, and high quality data were required for this pragmatic international nursing care clinical trial, which used a novel cluster cross-over design.

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. Methods: 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. Results: 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. Conclusion: Greater restriction in participation after stroke among women than men was mostly attributable to their advanced age and greater pre-stroke dependency. Interventions targeting participation could reduce the impact of stroke in women.

Background: The natural history of spontaneous intracerebral hematomas (ICH) is for variable degree of early hematoma retraction (HR), which may determine perihematomal brain edema (PHE), but such inter-relationships have not been rigorously studied. Methods: A pooled analysis of 760 computed tomography (CT) scans within 24±12 hours and 1197 CT scans within 72±12 hours of diagnostic CT (0-6 hours from symptom onset), from non-surgical ICH patients included in the Virtual International Stroke Trials Archive (VISTA), and INTERACT I, CLEAR III and MISTIE II clinical trials. Multivariable logistic regression was used to assess independent associations of HR and good 90-day functional outcome (modified Rankin scale [mRS] Results: Median (IQR) diagnostic ICH volume was 11.4 (6.1-22.8) mL. HR occurred at defined thresholds in 5.8% (3mL), 2.4% (6mL) and 2.8% (33%), and in 10.3%, 4.0% and 4.6%, at 24 and 72 hours, respectively. Median retraction volumes at 24/72 hours were -0.9[-2.2, -0.3] and -1.2[-2.9, -0.5) mL, respectively. Between 13.2% and 24% of patients met common hematoma expansion definitions. Clot retraction volume at 24/72 hours was significantly correlated with diagnostic ICH volume (Spearman’s rho: -0.65/-0.64; p5mL had good outcome (N = 20). Conclusion: HR is uncommon and continues to increase over first 72 hours after ICH. Greater HR is associated with more severe ICH, but with less PHE volume, and predicts a poor outcome. Further study is required to better understand these findings.

Introduction: As large clinical trials for spontaneous intracerebral hemorrhage (ICH) increasingly influence management, recruitment of diverse populations must be ensured to fully understand the disease process and benefit of interventions to the general public. There is little data on sex, race and outcomes in ICH trials. We hypothesize that women and geographic minorities are underrepresented in ICH clinical trials and that there exist population specific differences in mortality, functional outcomes and response to interventions. Methods: Pooled analysis of 5456 subjects from the following clinical trials: VISTA (985), INTERACT I (404) and II (2829), STICH II (597), MISTIE II (141) and CLEAR III (500). Patients were grouped by sex, race, and geographic location. Modified Rankin Scale [mRS] was obtained at 30 days and 3 months. Results: More men than women participated in ICH trials (61.9% vs. 38.1%); women were older and more likely to have hypertension; men had more coronary artery disease. Women presented with lower Glasgow Coma scale, higher ICH score and more intraventricular hemorrhage. Day 90 mortality was 13.9% in women and 16.6 % in men (p=0.01); 90 day poor outcome (mRS 3-5) was 57.2% in women and 51.0% in men (p Conclusions: Sex and race representation in ICH clinical trials only partially equate to current understanding of epidemiology of ICH. There is a lack of trial evidence from Africa and South America and under-representation of women, Hispanics and blacks. Despite higher ICH severity, Hispanics had lower adjusted mortality risk while males had higher risk and Arabics and blacks had worse adjusted poor outcomes.

Background and Purpose: As lower doses of alteplase reduce the risk of symptomatic intracerebral hemorrhage (sICH), older and Asian people may benefit more from low-dose alteplase than other patients with acute ischemic stroke (AIS). Methods: Data from the ENhanced Control of Hypertension ANd Thrombolysis strokE study (ENCHANTED), an international, multi-center, prospective, randomized, open-label, blinded-endpoint trial, were analyzed to assess effects of low- (0.6mg/kg body weight) vs. standard-dose (0.9mg/kg) alteplase in AIS patients, by age and ethnicity (Asian vs. non-Asian), pre-specified subgroup analyses, on key efficacy and safety outcomes. Results: 3297 patients (1248 female), mean age 67 years were included. After adjusting for baseline characteristics and management variables over the first seven days, increasing age was associated with poor outcome, defined by ordinal analysis of the modified Rankin score (mRS) (shift to a less favorable outcome, P trend Conclusions: Increasing age predicts poor outcome in thrombolysis-treated AIS patients. There was no heterogeneity in the treatment effects of low- vs. standard-dose alteplase. Decisions about intravenous thrombolysis should be based on variables other than age and ethnicity.

Introduction: Women have been reported to receive evidence-based care less often than men, but it is uncertain whether this contributes to sex differences in outcomes after stroke. We examined this using data obtained from the Australian Stroke Clinical Registry (AuSCR). Methods: We included first-ever strokes admitted to 40 hospitals participating in the AuSCR during 2010-2013. Mortality one year after stroke was obtained from linkage to the National Death Index. Multilevel Poisson modelling, accounting for hospital, was used to estimate the mortality rate ratio (MRR) for women compared to men. Multivariable models were adjusted for sociodemographics, stroke type, severity (ability to walk on admission) and the provision of evidence-based therapies while in hospital (stroke unit care, thrombolysis, secondary prevention medications, dysphagia screening and mobilization). Results: Data were available for 9,549 strokes (47% women, 80% ischaemic stroke). Women, compared to men, were older (mean [SD] 75.0 [15.0] vs 70.3 [13.9], pcrude 1.42 [95% CI 1.31, 1.55]). This association was attenuated when adjusting for age and severity of stroke (MRR adjusted 1.00 [95% CI 0.92, 1.09] but not by any of the evidence-based therapies. Conclusion: Greater mortality in women was associated with differences in age and stroke severity and not differences in access to care. Improvements in care for the elderly and the management of modifiable factors of stroke severity should reduce sex differences in outcomes.

Background and Purpose— High rates of ischemic stroke and poor adherence to secondary prevention measures are observed in the Chinese population. Methods— We used a national, multicenter, cluster-randomized controlled trial in which 47 hospitals were randomized to either a structured care program group (n=23) or a usual care group (n=24). The structured care program consisted of a specialist-administered, guideline-recommended pharmaceutical treatment and a lifestyle modification algorithm associated with written and Internet-accessed educational material for patients for the secondary prevention of ischemic stroke. The primary efficacy outcome was the proportion of patients who adhered to the recommended measures at 12-month postdischarge. This trial is registered with ClinicalTrial.gov (NCT00664846). Results— At 12 months, 1287 (72.1%) patients in the Standard Medical Management in Secondary Prevention of Ischemic Stroke in China (SMART) group and 1430 (72%) patients in the usual care group had completed the 12-month follow-up ( P =0.342). Compared with the usual care group, those in the SMART group showed higher adherence to statins (56% versus 33%; P =0.006) but no difference in adherence to antiplatelet (81% versus 75%; P =0.088), antihypertensive (67% versus 69%; P =0.661), or diabetes mellitus drugs (73% versus 67%; P =0.297). No significant difference in the composite end point (new-onset ischemic stroke, hemorrhagic stroke, acute coronary syndrome, and all-cause death) was observed (3.56% versus 3.59%; P =0.921). Conclusions— The implementation of a program to improve adherence to secondary ischemic stroke prevention efforts in China is feasible, but these programs had only a limited impact on adherence and no impact on 1-year outcomes. Further development of a structured program to reduce vascular events after stroke is needed. Clinical Trial Registration—URL: http://www.clinicaltrials.gov . Unique identifier: NCT00664846.

Background and Purpose— Uncertainty exists over whether quality improvement strategies translate into better health-related quality of life (HRQoL) and survival after acute stroke. We aimed to determine the association of best practice recommended interventions and outcomes after stroke. Methods— Data are from the Australian Stroke Clinical Registry during 2010 to 2014. Multivariable regression was used to determine associations between 3 interventions: received acute stroke unit (ASU) care and in various combinations with prescribed antihypertensive medication at discharge, provision of a discharge care plan, and outcomes of survival and HRQoL (EuroQoL 5-dimensional questionnaire visual analogue scale) at 180 days, by stroke type. An assessment was also made of outcomes related to the number of processes patients received. Results— There were 17 585 stroke admissions (median age 77 years, 47% female; 81% managed in ASUs; 80% ischemic stroke) from 42 hospitals (77% metropolitan) assessed. Cumulative benefits on outcomes related to the number of care processes received by patients. ASU care was associated with a reduced likelihood of death (hazard ratio, 0.49; 95% confidence interval, 0.43–0.56) and better HRQoL (coefficient, 21.34; 95% confidence interval, 15.50–27.18) within 180 days. For those discharged from hospital, receiving ASU+antihypertensive medication provided greater 180-day survival (hazard ratio, 0.45; 95% confidence interval, 0.38–0.52) compared with ASU care alone (hazard ratio, 0.64; 95% confidence interval, 0.54–0.76). HRQoL gains were greatest for patients with intracerebral hemorrhage who received care bundles involving discharge processes (range of increase, 11%–19%). Conclusions— Patients with stroke who receive best practice recommended hospital care have improved long-term survival and HRQoL.

The burden of stroke on individuals, families, healthcare systems, and societies in Asia is enormous and increasing in relation to rapid sociodemographic and lifestyle changes in a large and diverse range of populations. However, challenges also present opportunities for experts from within and outside Asia to facilitate improvements in population health through advocacy, engagement, training, and the conduct and promotion of evidence-based strategies. With a total population that exceeds 4 billion, over half of the world’s population, increasing numbers of patients are accessing clinical services, technologies, and databases, and clinicians are gaining training, experience, and reliable information on a broad range of aspects of stroke care. Clinical research experience is improving through international links and fellowships, and health professionals from the region are eager to engage (and prove themselves) through participation in high-quality research and clinical practice. The Asia Pacific Stroke Organization (APSO) covers a vast and heterogenous geographical area, with much variability in language, governments, culture, historical links, socioeconomic development, and organization of health services. APSO seeks to improve the standard of stroke care in the whole region by improving communication and cooperation between stroke professionals and organizations in the region and peers in other regions, by means of annual congresses, workshops, and continued medical education. In the past year, we have achieved this through strengthened cooperation with other organizations such as the European Stroke Organization and the Asia-Oceanian Society for Neurorehabilitation and increased participation by nurses and other health professionals and had active consultation with nongovernmental organizations with shared commitments to those affected by stroke. APSO originated from an amalgamation of the Asian Stroke Forum and Asia Pacific Conference Against Stroke. Before September 2009, these organizations held large annual conferences, independently: Asian Stroke Forum, primarily based in Japan, had conferences in Tokyo and Kyoto, in 2005 and 2007, …

Background and Aim: There is little evidence on the prognostic significance of hyponatremia in patients with intracerebral hemorrhage (ICH). The aim of this study was to clarify the association of hyponatremia with clinical outcomes and to determine the relationship between hyponatremia and hematoma and perihematomal edema growth. Methods: This study was a subsidiary, post-hoc analysis of INTERACT 1 and 2; which were randomised controlled trials of patients with acute spontaneous ICH with elevated systolic blood pressure (BP), randomly assigned to intensive (target systolic BP < 140 mmHg) or guideline-based (< 180 mmHg) BP management. Hyponatremia was defined as serum sodium < 135 mEq/L. The primary clinical outcome was death at 90 days. The outcomes of the CT substudies were absolute growth of hematoma and perihematomal edema volume in 24 hours. Results: Among 3002 patients with information on sodium and clinical outcomes, 349 (12%) had hyponatremia, which was associated with death at 90 days (multivariable-adjusted OR, 2.03; 95% CI, 1.41-2.91; p=0.0001). In the hematoma growth and perihematomal edema growth analyses, there were 1241 and 790 patients included, respectively. No associations were observed for hematoma growth or perihematomal edema growth during the first 24 hours. Conclusions: Hyponatremia is associated with higher mortality at 90 days in patients with spontaneous ICH. Hyponatremia does not appear to affect perihematomal edema growth or hematoma volume growth.