Interhospital Transfer for Endovascular Stroke Treatment in Canada: Results From the OPTIMISE Registry.

BACKGROUND: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. METHODS: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. RESULTS: Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. CONCLUSIONS: Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.

Time Course of Early Hematoma Expansion in Acute Spot-Sign Positive Intracerebral Hemorrhage: Prespecified Analysis of the SPOTLIGHT Randomized Clinical Trial.

BACKGROUND: In the SPOTLIGHT trial (Spot Sign Selection of Intracerebral Hemorrhage to Guide Hemostatic Therapy), patients with a computed tomography (CT) angiography spot-sign positive acute intracerebral hemorrhage were randomized to rFVIIa (recombinant activated factor VIIa; 80 µg/kg) or placebo within 6 hours of onset, aiming to limit hematoma expansion. Administration of rFVIIa did not significantly reduce hematoma expansion. In this prespecified analysis, we aimed to investigate the impact of delays from baseline imaging to study drug administration on hematoma expansion. METHODS: Hematoma volumes were measured on the baseline CT, early post-dose CT, and 24 hours CT scans. Total hematoma volume (intracerebral hemorrhage+intraventricular hemorrhage) change between the 3 scans was calculated as an estimate of how much hematoma expansion occurred before and after studying drug administration. RESULTS: Of the 50 patients included in the trial, 44 had an early post-dose CT scan. Median time (interquartile range) from onset to baseline CT was 1.4 hours (1.2-2.6). Median time from baseline CT to study drug was 62.5 (55-80) minutes, and from study drug to early post-dose CT was 19 (14.5-30) minutes. Median (interquartile range) total hematoma volume increased from baseline CT to early post-dose CT by 10.0 mL (-0.7 to 18.5) in the rFVIIa arm and 5.4 mL (1.8-8.3) in the placebo arm (P=0.96). Median volume change between the early post-dose CT and follow-up scan was 0.6 mL (-2.6 to 8.3) in the rFVIIa arm and 0.7 mL (-1.6 to 2.1) in the placebo arm (P=0.98). Total hematoma volume decreased between the early post-dose CT and 24-hour scan in 44.2% of cases (rFVIIa 38.9% and placebo 48%). The adjusted hematoma growth in volume immediately post dose for FVIIa was 0.998 times that of placebo ([95% CI, 0.71-1.43]; P=0.99). The hourly growth in FFVIIa was 0.998 times that for placebo ([95% CI, 0.994-1.003]; P=0.50; Table 3). CONCLUSIONS: In the SPOTLIGHT trial, the adjusted hematoma volume growth was not associated with Factor VIIa treatment. Most hematoma expansion occurred between the baseline CT and the early post-dose CT, limiting any potential treatment effect of hemostatic therapy. Future hemostatic trials must treat intracerebral hemorrhage patients earlier from onset, with minimal delay between baseline CT and drug administration. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01359202.

Interobserver agreement of ASPECT score distribution for noncontrast CT, CT angiography, and CT perfusion in acute stroke.

BACKGROUND AND PURPOSE: The Alberta Stroke program early CT score (ASPECTS) is a semiquantative scale for estimating extent and distribution of early ischemic changes within the MCA territory in the acute stroke setting. Good interobserver agreement of total ASPECTS is demonstrated for noncontrast CT (NCCT) and other imaging modalities. Our purpose is to assess interobserver agreement for individual ASPECTS regions for different imaging modalities. METHODS: One hundred and eighty-one consecutive patients presenting with acute stroke symptoms within 4.5 hours of onset were included. Four readers assigned total and individual ASPECTS for NCCT, CT angiography source images (CTA-SI), and CTP maps of cerebral blood volume (CTP-CBV). Interobserver agreement was assessed by measuring internal consistency and concordance of total and individual ASPECTS using Cronbach's α and intraclass correlation coefficient, respectively. RESULTS: Total ASPECTS demonstrated very good concordance and internal consistency for all 3 modalities. Intraclass correlation coefficient and Cronbach's α were 0.834 and 0.859 for NCCT, 0.876 and 0.894 for CTA, and 0.903 and 0.911 for CTP-CBV, respectively. Performance for individual ASPECTS regions was inferior to total ASPECTS, but incremental improvement in interobserver reliability was demonstrated for NCCT, CTA-SI, and CTP-CBV, respectively. Highest concordance was shown for caudate, lentiform, and M1-M3, whereas performance for internal capsule and M4-M6 was poorer. CONCLUSIONS: CTP-CBV demonstrates the highest interobserver agreement for individual ASPECTS regions.

Short-term outcomes after symptomatic internal carotid artery occlusion.

BACKGROUND AND PURPOSE: Previous studies concerning internal carotid artery (ICA) occlusion have focused on long-term prognosis. The purpose of the present study was to evaluate short-term outcomes of patients with symptomatic ICA occlusion. METHODS: We used data from the Registry of the Canadian Stroke Network on consecutive patients presenting to 11 stroke centers in Ontario. We included patients with noncardioembolic ischemic stroke or transient ischemic attack within the anterior circulation. The resulting cohort was divided into 4 groups based on vascular imaging of the ipsilateral extracranial ICA: occlusion, severe stenosis, moderate stenosis, and mild/no stenosis. Logistic regression modeling was used to evaluate the association between the degree of stenosis/occlusion of the symptomatic ICA and a series of short-term outcome measures. RESULTS: Of the 4144 patients who met study criteria, 283 patients had a symptomatic ICA occlusion. Compared with patients with ICA occlusion, patients with all other degrees of stenosis had a lower risk of in-hospital death, neurological worsening, and poor functional outcome. Particularly, severe stenosis was associated with a lower risk of in-hospital death (adjusted OR, 0.40; 95% CI, 0.20 to 0.79), neurological worsening (adjusted OR, 0.52; 95% CI, 0.34 to 0.78), and poor functional outcome (adjusted OR, 0.62; 95% CI, 0.41 to 0.94) compared with the ICA occlusion group. CONCLUSIONS: The results of our study showed that patients with symptomatic ICA occlusion are at a high risk of adverse outcomes that is as severe, if not worse, than any other degree of ICA stenosis in the short term. Thus, more aggressive management may be warranted for patients with acute, symptomatic ICA occlusion.

Recanalization following Endovascular treatment and imaging of PErfusion, Regional inFarction and atrophy to Understand Stroke Evolution-NA1 (REPERFUSE-NA1).

RATIONALE: Following endovascular treatment, poor clinical outcomes are more frequent if the initial infarct core or volume of irreversible brain damage is large. Clinical outcomes may be improved using neuroprotective agents that reduce stroke volume and improve recovery. AIM: The aim of the REPERFUSE NA1 was to replicate the preclinical neuroprotection study that significantly reduced infarct volume in a primate model of ischemia reperfusion. Specifically, REPERFUSE NA1 will determine if administration of the neuroprotectant NA1 prior to endovascular therapy can significantly reduce early (Day 2 subtract Day 1 diffusion-weighted imaging volume) and delayed secondary infarct (90-day whole brain atrophy plus FLAIR volume-Day 1 diffusion-weighted imaging volume) growth, as measured by magnetic resonance imaging. METHODS AND DESIGN: REPERFUSE-NA1 is a magnetic resonance imaging observational substudy of ESCAPE-NA1 (ClinicalTrialGov NCT02930018). A total of 150 acute stroke patients will be recruited (including 20% attrition) that have been randomized to either NA1 or placebo in the ESCAPE-NA1 trial. STUDY OUTCOMES: Primary-Early infarct growth measured using diffusion-weighted imaging will be at least 30% smaller in patients receiving NA1 compared to placebo. Secondary-Delayed secondary stroke injury at 90 days will be significantly reduced in patients receiving NA1 compared to placebo, as well as delayed secondary growth at 90 days. CONCLUSION: REPERFUSE-NA1 will demonstrate the effect of NA1 neuroprotection on reducing the early and delayed stroke injury after reperfusion treatment.

Social, financial and psychological stress during an emerging pandemic: observations from a population survey in the acute phase of COVID-19.

INTRODUCTION: The negative impacts of COVID-19 have rippled through every facet of society. Understanding the multidimensional impacts of this pandemic is crucial to identify the most critical needs and to inform targeted interventions. This population survey study aimed to investigate the acute phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress between 3 April and 15 May 2020. METHODS: 6040 participants are included in this report. A multivariate linear regression model was used to identify factors associated with stress changes (as measured by the Cohen's Perceived Stress Scale (PSS)) relative to pre-outbreak retrospective estimates. RESULTS: On average, PSS scores increased from low stress levels before the outbreak to moderate stress levels during the outbreak (p<0.001). The independent factors associated with stress worsening were: having a mental disorder, female sex, having underage children, heavier alcohol consumption, working with the general public, shorter sleep duration, younger age, less time elapsed since the start of the outbreak, lower stress before the outbreak, worse symptoms that could be linked to COVID-19, lower coping skills, worse obsessive-compulsive symptoms related to germs and contamination, personalities loading on extraversion, conscientiousness and neuroticism, left wing political views, worse family relationships and spending less time exercising and doing artistic activities. CONCLUSION: Cross-sectional analyses showed a significant increase from low to moderate stress during the COVID-19 outbreak. Identified modifiable factors associated with increased stress may be informative for intervention development. TRIAL REGISTRATION NUMBER: NCT04369690; Results.

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative: study protocol and rationale of a multicentre retrospective individual patient data meta-analysis.

INTRODUCTION: Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. METHODS AND ANALYSIS: The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence. ETHICS AND DISSEMINATION: Ethical approval for the GOAL study has already been obtained from the Medical Review Ethics Committee region Arnhem-Nijmegen. Additionally and when necessary, approval will also be obtained from national or local institutional review boards in the participating centres. When needed, a standardised data transfer agreement will be provided for participating centres. We plan dissemination of our results in peer-reviewed international scientific journals and through conference presentations. We expect that the results of this unique study will lead to better understanding of worldwide differences in risk factors, causes and outcome of young stroke patients.

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease.

Next-generation sequencing (NGS) is quickly revolutionizing how research into the genetic determinants of constitutional disease is performed. The technique is highly efficient with millions of sequencing reads being produced in a short time span and at relatively low cost. Specifically, targeted NGS is able to focus investigations to genomic regions of particular interest based on the disease of study. Not only does this further reduce costs and increase the speed of the process, but it lessens the computational burden that often accompanies NGS. Although targeted NGS is restricted to certain regions of the genome, preventing identification of potential novel loci of interest, it can be an excellent technique when faced with a phenotypically and genetically heterogeneous disease, for which there are previously known genetic associations. Because of the complex nature of the sequencing technique, it is important to closely adhere to protocols and methodologies in order to achieve sequencing reads of high coverage and quality. Further, once sequencing reads are obtained, a sophisticated bioinformatics workflow is utilized to accurately map reads to a reference genome, to call variants, and to ensure the variants pass quality metrics. Variants must also be annotated and curated based on their clinical significance, which can be standardized by applying the American College of Medical Genetics and Genomics Pathogenicity Guidelines. The methods presented herein will display the steps involved in generating and analyzing NGS data from a targeted sequencing panel, using the ONDRISeq neurodegenerative disease panel as a model, to identify variants that may be of clinical significance.