Association Between Time to Treatment With Endovascular Thrombectomy and Home-Time After Acute Ischemic Stroke.

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

Time From Hospital Arrival Until Endovascular Thrombectomy and Patient-Reported Outcomes in Acute Ischemic Stroke.

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

Effect of Endovascular Thrombectomy for Acute Ischemic Stroke on Cognitive Outcomes: A Secondary Analysis of the ESCAPE Trial.

BACKGROUND AND OBJECTIVES: The effect of endovascular therapy (EVT) for large vessel occlusion stroke on cognitive outcomes is not well understood. We evaluated the effect of EVT on cognitive function in the Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE) trial. METHODS: Patient data from the ESCAPE randomized trial were analyzed. Cognitive assessments completed at 90 days after stroke were the Montreal Cognitive Assessment (MoCA), the Sunnybrook Neglect Assessment Procedure (SNAP), the Boston Naming Test (BNT), Trail-making test A (Trails A), and Trail-making test B (Trails B). We used logistic regression to evaluate the association between EVT and favorable cognitive outcome on the 5 separate tests, adjusting for demographic and clinical factors. We used generalized estimating equations and ordinal regression to determine the odds of favorable outcome with EVT on global cognition incorporating the 5 tests. We added final infarct volume (FIV) to the models to assess the relationship of FIV with cognitive outcome. RESULTS: The ESCAPE trial included 315 patients, 165 randomized to EVT and 150 randomized to control. There was higher odds of favorable outcome with EVT for MoCA (adjusted odds ratio [aOR] 2.32, 95% CI 1.30-4.16), SNAP (aOR 3.85, 95% CI 2.00-7.45), BNT (aOR 2.33, 95% CI 1.30-4.17), trails A (aOR 3.50, 95% CI 1.93-6.36), and trails B (aOR 2.56, 95% CI 1.46-4.48). There was higher odds of favorable outcome with EVT on global binary (aOR 2.57, 95% CI 1.67-3.94) and ordinal analyses (aOR 2.83, 95% CI 1.68-4.76) of cognitive function. After adding FIV to the models, both FIV and EVT were significantly associated with cognitive outcome. There was a significant correlation between global cognitive performance and mRS at day 90 (r = -0.78, p < 0.001), with the largest reductions in favorable cognitive outcome from mRS score 4 to 5 and from mRS 2 to 3. DISCUSSION: In this secondary analysis of the ESCAPE trial, EVT was associated with favorable outcome on 5 separate cognitive tests and in global analyses of cognitive benefit. These results provide novel evidence for the effect of EVT on cognition and support the global benefit of treatment with EVT. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in patients with acute ischemic stroke due to intracranial internal carotid artery (ICA) or M1 segment MCA occlusion, including tandem extracranial ICA occlusions, EVT compared with best medical therapy increased odds of favorable cognitive outcome.

Population Trends of New Prescriptions for Antihyperglycemics and Antihypertensives Between 2014 and 2022.

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

Magnetic Resonance Imaging Assists With Determining Etiology After Transient Ischemic Attack or Minor Stroke.

BACKGROUND: Magnetic resonance imaging infarct topography may assist with determining stroke etiology. The influence of diffusion-weighted imaging (DWI)-positive lesions on etiology determination in patients with transient ischemic attack or minor stroke is not well studied. METHODS AND RESULTS: We prospectively enrolled patients between 2010 and 2017 in 2 studies; participants with a final diagnosis of probable or definite transient ischemic attack or stroke were pooled for analysis. The primary outcome was the adjudicated ischemic etiology. We compared proportion of each etiology (cardioembolic, large-vessel, small-vessel disease, other) in patients who had DWI positivity compared with DWI negativity. We used logistic regression to determine the adjusted odds ratio (OR) for each etiology compared with undetermined by DWI positivity. The final analysis included 1498 patients: 832 (55.5%) were DWI-positive. DWI-positive patients were more likely to be diagnosed with small-vessel disease (19.1% versus 5.3%) and less likely with undetermined etiology (36.9% versus 53.0%; P<0.001). After adjustment, the presence of any DWI lesion was associated with increased odds of assigning any etiology (OR, 1.8 [95% CI, 1.3-2.5]). A single DWI lesion was associated with increased odds of small-vessel disease diagnosis (OR, 9.5 [95% CI, 6.4-14.0]), and multiple DWI lesions with reduced odds of small-vessel disease (OR, 0.2 [95% CI, 0.1-0.4]) but increased odds of all other etiologies compared with undetermined etiology. CONCLUSIONS: Any DWI-positive lesion after suspected transient ischemic attack or minor stroke was associated with increased odds of assigning a etiology. Presence and topography of DWI lesions on magnetic resonance imaging may assist with etiology determination and may impact stroke prevention therapies.

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

BACKGROUND: Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada. METHODS: We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models' discriminative values using Uno's c-statistic, comparing models with versus without PaSSV. RESULTS: We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable. CONCLUSION: PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

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

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

Blood Pressure Trajectories and Outcomes After Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Data on systolic blood pressure (SBP) trajectories in the first 24 hours after endovascular thrombectomy (EVT) in acute ischemic stroke are limited. We sought to identify these trajectories and their relationship to outcomes. METHODS: We combined individual-level data from 5 studies of patients with acute ischemic stroke who underwent EVT and had individual blood pressure values after the end of the procedure. We used group-based trajectory analysis to identify the number and shape of SBP trajectories post-EVT. We used mixed effects regression models to identify associations between trajectory groups and outcomes adjusting for potential confounders and reported the respective adjusted odds ratios (aORs) and common odds ratios. RESULTS: There were 2640 total patients with acute ischemic stroke included in the analysis. The most parsimonious model identified 4 distinct SBP trajectories, that is, general directional patterns after repeated SBP measurements: high, moderate-high, moderate, and low. Patients in the higher blood pressure trajectory groups were older, had a higher prevalence of vascular risk factors, presented with more severe stroke syndromes, and were less likely to achieve successful recanalization after the EVT. In the adjusted analyses, only patients in the high-SBP trajectory were found to have significantly higher odds of early neurological deterioration (aOR, 1.84 [95% CI, 1.20-2.82]), intracranial hemorrhage (aOR, 1.84 [95% CI, 1.31-2.59]), mortality (aOR, 1.75 [95% CI, 1.21-2.53), death or disability (aOR, 1.63 [95% CI, 1.15-2.31]), and worse functional outcomes (adjusted common odds ratio,1.92 [95% CI, 1.47-2.50]). CONCLUSIONS: Patients follow distinct SBP trajectories in the first 24 hours after an EVT. Persistently elevated SBP after the procedure is associated with unfavorable short-term and long-term outcomes.

Depressive symptoms among adults: Baseline findings of PURE Malaysia cohort study.

Introduction: In Malaysia, the prevalence of depression has increased from 1.8 % to 2.3 % within a decade. Thus, this study was performed to identify depressive symptoms and its associated factors among Malaysian adults. Methods: A cross-sectional study was conducted among the adult population aged 35-70 residing in rural and urban areas in Malaysia. Depressive symptoms were assessed using the short form Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) Composite International Diagnostic Interview (CIDI) questionnaire. Logistic regression models were fitted to identify the associated factors related to depressive symptoms. Results: About 3.7 % (95 % CI: 2.33-4.83) of the respondents reported having depressive symptoms. Younger adults aged 35-40 years old (AOR: 3.087; 95 % CI: 2.021-4.717), females (AOR: 2.318; 95 % CI: 1.669-3.219), widows and divorcees (AOR: 2.294; 95 % CI: 1.085-4.848), smokers (AOR: 1.843; 95 % CI: 1.334-2.545) and alcohol consumers (AOR: 1.843; 95 % CI: 1.264-2.688) showed a higher odds compared to their other counterparts. Underweight individuals (AOR: 1.899; 95 % CI: 1.177-3.065) and those diagnosed either with hypertension (AOR: 1.442; 95 % CI: 1.11-1.873), diabetes (AOR: 1.554; 95 % CI: 1.133-2.13), angina (AOR: 2.73; 95 % CI: 1.596-4.67), COPD (AOR: 4.187; 95 % CI: 1.528-11.472) or asthma (AOR: 1.906; 95 % CI: 1.309-2.774) were more likely to have depressive symptoms. Additionally, individuals with difficulty trusting people (AOR: 1.477; 95 % CI: 1.024-2.13) and those reported to experience either home or work-related stress (AOR: 2.584; 95 % CI: 2.003-3.331) were more prone to have depressive symptoms. Conclusion: In this broad population-based study, about 3.7 % (95 % CI: 2.33-4.83) of respondents reported having depressive symptoms. Timely and well targeted collaborative intervention on the identified risk factors by the relevant authorities, would mitigate their effect on the quality of life and retard the progression into depression, especially among younger adults.

Presenting Symptoms and Diffusion-Weighted MRI Positivity by Time After Transient Neurologic Events: A Pooled Analysis of 3 Cohort Studies

BACKGROUND AND OBJECTIVE: The association between focal vs nonfocal presenting symptom and diffusion-weighted imaging (DWI) positivity in relation to onset-to-imaging time in patients with transient neurologic events remains unclear. We hypothesize that episodes consisting of focal symptoms would have proportionally higher DWI-positive imaging at later onset-to-imaging times. METHODS: Patients with transient neurologic symptoms and a normal neurologic examination who had DWI in the combined data set of 3 cohort studies were included. We used logistic regression models to evaluate the association between each type of presenting symptom (motor weakness, speech impairment, sensory symptoms, vision loss, diplopia, gait instability, dizziness, headache, presyncope, and amnesia) and DWI positivity after adjusting for clinical variables (age, sex, history of stroke, dyslipidemia, coronary artery disease, atrial fibrillation, symptoms duration [<10, 10-59, ≥60 minutes, or unclear], and study source). We stratified the results by onset-to-imaging time categories (<6 hours, 6-23 hours, and ≥24 hours). RESULTS: Of the total 2,411 patients (1,345 male, median age 68 years), DWI-positive lesions were detected in 598 patients (24.8%). The prevalence of DWI positivity was highest in those with motor weakness (34.7%), followed by speech impairment (33.5%). In a multivariable analysis, the presence of motor weakness, speech impairment, and sensory symptoms was associated with DWI positivity, while vision loss and headache were associated with lower odds of DWI positivity, but nevertheless had 13.6% and 15.3% frequency of DWI positive. The odds of being DWI positive varied by onset-to-imaging time categories for motor weakness, with greater odds of being DWI positive at later imaging time (<6 hours: odds ratio [OR] 1.25, 95% confidence interval [CI] 0.84-1.87; 6-23 hours: OR 2.24, 95% CI 1.47-3.42; and ≥24 hours: OR 2.42, 95% CI 1.74-3.36; interaction p = 0.033). Associations of other symptoms with DWI positivity did not vary significantly by time categories. DISCUSSION: We found that onset-to-imaging time influences the relationship between motor weakness and DWI positivity in patients with transient neurologic events. Compared with motor, speech, and sensory symptoms, visual or nonfocal symptoms carry a lower but still a substantive association with DWI positivity.

Mediation of Post-Stroke Function by Cognition in the Canadian Longitudinal Study on Aging.

INTRODUCTION: Cognitive and functional impairment after stroke are common, but the relation between cognitive and functional decline after stroke is not well studied. METHODS: We used the comprehensive cohort in the Canadian Longitudinal Study on Aging to identify those with prior stroke, and we calculated reliable cognitive change scores from baseline to follow-up for the memory and executive domains. Functional decline was defined as an increase in the number of dependent daily activities. Using formal mediation analysis, we tested the presence and degree of mediation of the association between stroke and functional decline by cognitive decline. RESULTS: There were 22,648 individuals with memory change scores (325 with stroke) and 17,613 individuals with executive change scores (241 with stroke). History of stroke was significantly associated with memory decline (-0.26 standard deviations, 95% CI -0.33 to -0.19), executive decline (-0.22, 95% CI -0.36 to -0.09), and new functional impairment (adjusted odds ratio 2.31, 95% CI 1.80-2.97) over a median of 3-year follow-up. Cognitive decline was a significant mediator of functional decline. Memory decline mediated only 5% of the relationship, whereas executive and overall cognitive decline mediated 13% and 22%, respectively. CONCLUSION: Cognitive decline is a mediator of the association between prior stroke and functional decline; consequently, strategies to delay, attenuate, or prevent cognitive decline after stroke may be important to preserving long-term functional status.

Association between blood pressure variability and outcomes after endovascular thrombectomy for acute ischemic stroke: An individual patient data meta-analysis.

INTRODUCTION: Data on the association between blood pressure variability (BPV) after endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) and outcomes are limited. We sought to identify whether BPV within the first 24 hours post EVT was associated with key stroke outcomes. METHODS: We combined individual patient-data from five studies among AIS-patients who underwent EVT, that provided individual BP measurements after the end of the procedure. BPV was estimated as either systolic-BP (SBP) standard deviation (SD) or coefficient of variation (CV) over 24 h post-EVT. We used a logistic mixed-effects model to estimate the association [expressed as adjusted odds ratios (aOR)] between tertiles of BPV and outcomes of 90-day mortality, 90-day death or disability [modified Rankin Scale-score (mRS) > 2], 90-day functional impairment (⩾1-point increase across all mRS-scores), and symptomatic intracranial hemorrhage (sICH), adjusting for age, sex, stroke severity, co-morbidities, pretreatment with intravenous thrombolysis, successful recanalization, and mean SBP and diastolic-BP levels within the first 24 hours post EVT. RESULTS: There were 2640 AIS-patients included in the analysis. The highest tertile of SBP-SD was associated with higher 90-day mortality (aOR:1.44;95% CI:1.08-1.92), 90-day death or disability (aOR:1.49;95% CI:1.18-1.89), and 90-day functional impairment (adjusted common OR:1.42;95% CI:1.18-1.72), but not with sICH (aOR:1.22;95% CI:0.76-1.98). Similarly, the highest tertile of SBP-CV was associated with higher 90-day mortality (aOR:1.33;95% CI:1.01-1.74), 90-day death or disability (aOR:1.50;95% CI:1.19-1.89), and 90-day functional impairment (adjusted common OR:1.38;95% CI:1.15-1.65), but not with sICH (aOR:1.33;95% CI:0.83-2.14). CONCLUSIONS: BPV after EVT appears to be associated with higher mortality and disability, independently of mean BP levels within the first 24 h post EVT. BPV in the first 24 h may be a novel target to improve outcomes after EVT for AIS.

Transcranial Doppler ultrasound to evaluate the risk of hyperperfusion after endovascular stroke thrombectomy.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) has been reported in up to 50% of acute ischemic stroke (AIS) patients with a large vessel occlusion (LVO) treated with endovascular thrombectomy (EVT). HT may be driven by postrecanalization hyperperfusion injury and is independently associated with worse functional outcomes. Strategies to identify patients at risk for HT may assist in developing preventive therapies. METHODS: We prospectively included adult AIS patients with an anterior circulation LVO achieving successful recanalization after EVT. Consenting participants received transcranial Doppler ultrasound (TCD) within 18 hours of procedure completion. We compared flow velocities according to the presence of HT on the computed tomography scan performed within the first 24±12 hours from the end of EVT. We also evaluated the association of flow velocities with systemic blood pressure (BP) readings at the time of insonation. RESULTS: A total of 48 patients consented to participate in the study. Six (12%) were excluded due to the absence of temporal windows. HT was detected in 20 participants (48%). Those with HT had higher peak systolic velocities on the middle cerebral arteries compared to those without HT for both the symptomatic (107±42 vs. 82±25 cm/second, p = .024) and asymptomatic (97±21 vs. 81±25 cm/second, p = .040) sides. No correlation of flow velocities on either the symptomatic or asymptomatic side and BP measurements at the time of insonation was detected. CONCLUSION: TCD can identify patients at risk of HT following successful EVT. TCD could serve as an inexpensive ancillary test to guide participant selection for clinical trials targeting postprocedural reperfusion injury.

Cognitive performance following stroke, transient ischaemic attack, myocardial infarction, and hospitalisation: an individual participant data meta-analysis of six randomised controlled trials.

BACKGROUND: Survivors of stroke are often concerned about cognitive problems, and information on the risk of cognitive problems often comes from small studies. We aimed to estimate years of cognitive ageing associated with stroke compared with transient ischaemic attack, myocardial infarction, and other hospitalisations in a large population. METHODS: Using data from six randomised controlled trials (ORIGIN, ONTARGET, TRANSCEND, COMPASS, HOPE-3, and NAVIGATE ESUS), we completed an individual participant data meta-analysis using data requested from the Public Health Research Institute to estimate the association of stroke (by type and severity), transient ischaemic attack, myocardial infarction, and other hospitalisations with cognitive performance measured at the end of each trial. We included participants in any of these randomised controlled trials with a cognitive assessment at baseline and at least one other timepoint. Cognitive performance was measured with the Mini-Mental State Examination or the Montreal Cognitive Assessment, transformed into Z scores. We estimated Z score differences in end of trial cognitive performance between people with and without events and calculated corresponding years of cognitive ageing in these trials, and additionally calculated using a population representative cohort-the Cognitive Function and Ageing Study. FINDINGS: In 64 106 participants from 55 countries, compared with no event, stroke was associated with 18 years of cognitive ageing (1487 strokes included in the model, 95% CI 10 to 28; p<0·0001) and transient ischaemic attack with 3 years (660 transient ischaemic attacks included in the model, 0 to 6; p=0·021). Myocardial infarction (p=0·60) and other hospitalisations (p=0·26) were not associated with cognitive ageing. The mean difference in SD compared with people without an event was -0·84 (95% CI -0·91 to -0·76; p<0·0001) for disabling stroke, and -0·12 (-0·19 to -0·05; p=0·0012) for non-disabling stroke. Haemorrhagic stroke was associated with worse cognition (-0·75, -0·95 to -0·55; p<0·0001) than ischaemic stroke (-0·42, -0·48 to -0·36; p <0·0001). INTERPRETATION: Stroke has a substantial effect on cognition. The effects of transient ischaemic attack were small, whereas myocardial infarction and hospitalisation had a neutral effect. Prevention of stroke could lead to a reduction in cognitive ageing in those at greatest risk. FUNDING: Population Health Research Institute and Chief Scientist Office of Scotland.

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

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

Higher Procedural Volumes Are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke.

OBJECTIVE: We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). METHODS: This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016 to December 31, 2019 in the Get with the Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment National Institutes of Health Stroke Scale (NIHSS) < 6, onset-to-treatment time > 6 hours, and interhospital transfers. There were 2 secondary cohorts: (1) the EVT metrics cohort excluded patients with missing data on time from door to arterial puncture and (2) the intravenous thrombolysis (IVT) metrics cohort only included patients receiving IVT ≤4.5 hours after onset. RESULTS: The primary cohort (mean ± standard deviation age = 70.7 ± 14.8 years; 51.2% female; median [interquartile range] baseline NIHSS = 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case increase in volume) of discharge to home (1.03 [1.02-1.04]), functional independence at discharge (1.02 [1.01-1.04]), and lower rates of in-hospital mortality (0.96 [0.95-0.98]). All secondary measures were also associated with procedural volumes. INTERPRETATION: Among AIS patients primarily presenting to EVT-capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality. ANN NEUROL 2023.

World-wide variations in tests of cognition and activities of daily living in participants of six international randomized controlled trials.

Background: Better understanding of worldwide variation in simple tests of cognition and global function in older adults would aid the delivery and interpretation of multi-national studies of the prevention of dementia and functional decline. Method: In six RCTs that measured cognition with the mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), and activities of daily living (ADL) with the Standardised Assessment of Everyday Global Activities (SAGEA), we estimated average scores by global region with multilevel mixed-effects models. We estimated the proportion of participants with cognitive or functional impairment with previously defined thresholds (MMSE≤24 or MoCA≤25, SAGEA≥7), and with a country-standardised z-score threshold of cognitive or functional score of ≤-1. Results: In 91,396 participants (mean age 66.6 years [SD 7.8], 31% females) from seven world regions, all global regions differed significantly in estimated cognitive function (z-score differences 0.11-0.45, p<0.001) after accounting for individual-level factors, centre and study. In different regions, the proportion of trial participants with MMSE≤24 or MoCA≤25 ranged from 23-36%; the proportion below a country-standardised z-score threshold of ≤1 ranged from 10-14%. The differences in prevalence of impaired IADL (SAGEA≥7) ranged from 2-6% and by country-standardised thresholds from 3-6%. Conclusions: Accounting for country-level factors reduced large differences between world regions in estimates of cognitive impairment. Measures of IADL were less variable across world regions, and could be used to better estimate dementia prevalence in large studies.

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

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

Association Between Duration of Transient Neurological Events and Diffusion-Weighted Brain Lesions.

Background The relationship between duration of transient neurological events and presence of diffusion-weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion-weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal-only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. Conclusions Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one-third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.

Association Between Excess Sleep Duration and Risk of Stroke: A Population-Based Study.

BACKGROUND: Excess sleep is associated with higher risk of stroke, but whether the risk is modified by age and if it remains elevated after accounting for the competing risk of death is not well understood. METHODS: We used nine years of the Canadian Community Health Survey between 2000 to 2016 to obtain self-reported sleep duration and created a cohort of individuals without prior stroke, heart disease, or cancer. We linked to hospital records to determine subsequent admissions or emergency department visits for acute stroke until December 31, 2017. We used Cox proportional hazard models to determine the association between sleep duration and risk of stroke, assessing for modification by age and sex and adjusting for demographic, vascular, and social factors. We obtained cumulative incidence of stroke accounting for the competing risk of death. RESULTS: There were 82,795 individuals in our cohort who met inclusion criteria and had self-reported sleep duration, with 1705 stroke events in follow-up. There was an association between excess sleep (≥10 h/night) and risk of stroke in those <70 years (fully adjusted hazard ratio 2.29, 95% CI 1.04-5.06), but not ≥70 years of age, with a similar association after accounting for the competing risk of death. CONCLUSION: Sleep duration ≥10 h/night is associated with increased risk of stroke in those <70 years of age. The findings support current guidelines for 7-9 h of sleep per night. Further research is needed to elucidate the relationship between sleep and cerebrovascular disease.