Publications by authors named "Dar Dowlatshahi"

177 Publications

How outcomes are measured after spontaneous intracerebral hemorrhage: A systematic scoping review.

PLoS One 2021 30;16(6):e0253964. Epub 2021 Jun 30.

Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Background And Purpose: Recovery after intracerebral haemorrhage (ICH) is often slower than ischemic stroke. Despite this, ICH research often quantifies recovery using the same outcome measures obtained at the same timepoints as ischemic stroke. The primary objective of this scoping review is to map the existing literature to determine when and how outcomes are being measured in prospective studies of recovery after ICH.

Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials and Web of Science from inception to November 2019, for prospective studies that included patients with ICH. Two investigators independently screened the studies and extracted data around timing and type of outcome assessment.

Results: Among the 9761 manuscripts reviewed, 395 met inclusion criteria, of which 276 were observational studies and 129 were interventional studies that enrolled 66274 patients. Mortality was assessed in 93% of studies. Functional outcomes were assessed in 85% of studies. The most frequently used functional assessment tool was the modified Rankin Scale (mRS) (60%), followed by the National Institute of Health Stroke Severity Scale (22%) and Barthel Index (21%). The most frequent timepoint at which mortality was assessed was 90 days (41%), followed by 180 days (18%) and 365 days (12%), with 2% beyond 1 year. The most frequent timepoint used for assessing mRS was 90 days (62%), followed by 180 days (21%) and 365 days (17%).

Conclusion: While most prospective ICH studies report mortality and functional outcomes only at 90 days, a significant proportion do so at 1 year and beyond. Our results support the feasibility of collecting long-term outcome data to optimally assess recovery in ICH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253964PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244847PMC
June 2021

Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments.

Neurology 2021 Jun 18. Epub 2021 Jun 18.

Ottawa Stroke Program. Division of Neurology, Department of Medicine, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada;

Objective: Hematoma expansion (HE) is commonly analyzed as a dichotomous outcome in intracerebral hemorrhage (ICH) trials. In this proof-of-concept study, we propose a "HE shift" analysis model as a method to improve the evaluation of candidate ICH therapies.

Methods: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, we performed HE shift analysis in response to intensive blood pressure lowering by generating polychotomous strata based on a) previously established HE definitions, b) percentile/absolute quartiles of hematoma volume change, and c) quartiles of 24-hour follow-up hematoma volumes. The relationship between blood pressure treatment and HE shift was explored using proportional odds models.

Results: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no HE. Using a trichotomous HE stratification, the highest strata of ≥33% revealed a 5.8% reduction in hematoma growth for those randomized to intensive therapy (aOR: 0.77 [95% CI: 0.60-0.99]). Using percentile quartiles of hematoma volume change, we observed a favorable shift to reduce growth in patients treated with intensive therapy: aOR: 0.73 (0.57-0.93). Similarly, in a tetrachotomous analysis of 24-hour follow-up hematoma volumes, shifts in the highest stratum (> 21.9 mL) was most notable.

Conclusions: Our findings suggest that intensive blood pressure reduction may preferentially mitigate growth in patients at risk of high volume HE. A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an additional way to assess hemostatic agents in future studies.

Registration: ClinicalTrials.gov Identifier: NCT01176565.
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http://dx.doi.org/10.1212/WNL.0000000000012393DOI Listing
June 2021

Short- and Long-term Health Care Resource Utilization and Costs Following Intracerebral Hemorrhage.

Neurology 2021 Jun 9. Epub 2021 Jun 9.

Division of Critical Care, Department of Medicine, University of Ottawa, Ottawa, ON, Canada.

Objective: We sought to evaluate the short- and long-term resource utilization and costs associated with ICH, taken from an entire population. We additionally sought to evaluate the association of oral anticoagulation (OAC) and healthcare costs.

Methods: Retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (2009-2017). We captured outcomes through linkage to health administrative databases. We used generalized linear models to identify factors associated with total cost. Analysis of OAC use was limited to patients ≥ 66 years. The primary outcome was total 1-year direct healthcare costs in 2020 US dollars.

Results: Among 16,248 individuals with ICH (mean age: 71.2 years, male: 52.3%), 1-year mortality was 46.0%, and 24.2% required mechanical ventilation. The median total 1-year cost was $26,886 [(interquartile range [IQR]) 9,641-62,907] with costs for those who died in hospital of $7,268 (IQR 4,031-14,966) versus $44,969 (IQR 20,264-82,414, < 0.001) for survivors to discharge. Oral anticoagulation (OAC) use (analysis limited to individuals ≥ 66 years old) was associated with higher total 1-year costs (cost ratio 1.06 [95% confidence interval: 1.01-1.11]). Total 1-year costs for the entire cohort exceeded $120 million per year over the study period.

Conclusions: ICH is associated with significant healthcare costs, and the median cost of an ICH patient is roughly 10-times the median inpatient cost in Ontario. Costs were higher among survivors than deceased patients. OAC use is independently associated with increased costs. In order to maximize cost-effectiveness, future therapies for ICH must aim to reduce disability, and not only improve mortality.
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http://dx.doi.org/10.1212/WNL.0000000000012355DOI Listing
June 2021

Association of apolipoprotein E variation with cognitive impairment across multiple neurodegenerative diagnoses.

Neurobiol Aging 2021 Apr 24. Epub 2021 Apr 24.

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.

For many years there has been uncertainty regarding how apolipoprotein E (APOE) E2 and E4 variants may influence overlapping features of neurodegeneration, such as cognitive impairment. We aimed to identify whether the APOE variants are associated with cognitive function across various neurodegenerative and cerebrovascular diagnoses (n = 513). Utilizing a comprehensive neuropsychology battery, multivariate multiple regression was used to assess the influence of APOE carrier status and disease cohort on performance across five cognitive domains. Irrespective of disease cohort, E4 carriers had significantly lower performance in verbal memory and visuospatial domains than those with E3/3, while E2 carriers' cognitive performance was not significantly different. However, E2 carriers with frontotemporal dementia (FTD) performed significantly worse than those with E3/3 in the attention/working memory, executive function, and visuospatial domains. Our results highlight that the influence of APOE variation on cognition is complex, in some cases varying based on diagnosis and possibly underlying disease pathology.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.04.011DOI Listing
April 2021

Observational Cross-Sectional Study of Inflammatory Markers After Transient Ischemic Attacks, Acute Coronary Syndromes, and Vascular Stroke Events.

CJC Open 2021 May 31;3(5):675-679. Epub 2020 Dec 31.

Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

We identified the prevalence of elevated high-sensitivity C-reactive protein and interleukin-6 in patients with recent cardiovascular (CV) events with or without prediabetes/diabetes, and in a control group of patients with remote CV events. Interleukin-6 was elevated in patients with prediabetes/diabetes and recent CV events (median, 4.84 pg/mL; interquartile range, 3.27-7.45) compared with patients with remote events (2.36 pg/mL; interquartile range, 1.09-4.00). There was a trend for elevated high-sensitivity C-reactive protein in patients with acute events and prediabetes/diabetes ( = 0.147). This supports the notion that patients with prediabetes/diabetes and recent CV events have higher inflammatory burdens than patients without recent CV events or dysglycemia.
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http://dx.doi.org/10.1016/j.cjco.2020.12.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134934PMC
May 2021

MRI-visible perivascular space volumes, sleep duration and daytime dysfunction in adults with cerebrovascular disease.

Sleep Med 2021 07 19;83:83-88. Epub 2021 Apr 19.

Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Medicine (Neurology), Sunnybrook Health Sciences Centre and University of Toronto, ON, Canada.

Objectives: Recent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.

Methods: We analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.

Results: Individuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38-22.26, p = 0.018).

Conclusions: Individuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.
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http://dx.doi.org/10.1016/j.sleep.2021.03.043DOI Listing
July 2021

Deferral of Consent: Recent Lessons From Canadian Acute Stroke Trials.

Stroke 2021 Jul 5;52(7):e326-e327. Epub 2021 May 5.

Ottawa Hospital and Department of Medicine, University of Ottawa (M.S., D.D.), Ontario, Canada.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034655DOI Listing
July 2021

Ticagrelor vs Clopidogrel in addition to Aspirin in minor ischemic stroke/ transient ischemic attack-Protocol for a systematic review and network meta-analysis.

PLoS One 2021 28;16(4):e0250553. Epub 2021 Apr 28.

University of Ottawa, School of Epidemiology and Public Health, Ottawa, Ontario, Canada.

Introduction: Patients with minor ischemic stroke or transient ischemic attack represent a high-risk population for recurrent stroke. No direct comparison exists comparing dual antiplatelet therapy regimens-namely, Ticagrelor and Aspirin versus Clopidogrel and Aspirin. This systematic review and network meta-analysis (NMA) will examine the efficacy of these two different antiplatelet regimens in preventing recurrent stroke and mortality up to 30 days.

Methods And Analysis: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched with the assistance of a medical information specialist. Two independent reviewers will screen studies for inclusion; eligible studies will include randomized controlled trials that enrolled adults presenting with acute minor ischemic stroke or transient ischemic attack and compared one or more of the interventions against each other and/or a control. The primary outcomes will be recurrent ischemic stroke up to 30 days from symptom onset. Secondary outcomes will include safety outcomes (I.e. major bleeding and mortality), functional disability, and outcomes up to 90 days from symptom onset. A Bayesian approach to NMA will be implemented using the BUGSnet function in R Software. Between group comparisons for time-to-event (TTE) and dichotomous outcomes will be presented in terms of hazard ratios and odds ratios with 95% credible intervals, respectively. Secondary effect measures of treatment ranking will also be estimated.

Ethics And Dissemination: No formal research ethics approval are necessary. We will disseminate our findings through scientific conference presentations, peer-reviewed publications, and social media/the press. The findings from this review will aid clinicians in decision-making on the choice of antithrombotic therapy in a high-risk stroke population and could be important in the development of future treatment trials and guidelines. Registration ID with Open Science Framework: 10.17605/OSF.IO/XDJYZ.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250553PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081237PMC
April 2021

Clinical Utility and Cost of Inpatient Transthoracic Echocardiography Following Acute Ischemic Stroke.

Neurohospitalist 2021 Jan 31;11(1):12-17. Epub 2020 Jul 31.

Department of Medicine (Neurology), Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada.

Background And Purpose: It is unclear whether it is clinically necessary or cost-effective to routinely obtain a transthoracic echocardiogram (TTE) during inpatient admission for ischemic stroke.

Methods: We assessed consecutive patients presenting with acute ischemic stroke at a comprehensive stroke center from 2015 to 2017 who underwent TTE. We assessed for findings on TTE that would warrant urgent intervention including cardiac thrombus, atrial myxoma, mitral stenosis, valve vegetation, valve dysfunction requiring surgery, and low ejection fraction. Subsequent changes in management included changes in anticoagulation, antibiotics, or valve surgery. We calculated in-hospital resource utilization and associated costs for inpatient TTE using individual direct cost details within a case-costing system.

Results: Of 695 patients admitted with acute ischemic stroke, 516 (74%) had a TTE and were included in our analysis. TTE findings were potentially clinically significant in 30 patients (5.8%) and changed management in 17 patients (3.3%). Inpatient admission was prolonged to expedite TTE in 24 patients, while TTE occurred after discharge in 76 patients. After correcting for the cost of TTE, the mean difference in cost to prolong an admission for TTE was $555.52 (USD), or $16 832 per change in management.

Conclusions: Given the low clinical utility of inpatient TTE after acute ischemic stroke and the costs associated with prolonging admission, discharge from hospital should not be delayed solely to obtain TTE.
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http://dx.doi.org/10.1177/1941874420946513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022191PMC
January 2021

The Story of Intracerebral Hemorrhage: From Recalcitrant to Treatable Disease.

Stroke 2021 May 8;52(5):1905-1914. Epub 2021 Apr 8.

Westchester Medical Center Health Network, Departments of Neurology and Neurosurgery, New York Medical College, Valhalla, NY (S.M.).

This invited special report is based on an award presentation at the World Stroke Organization/European Stroke Organization Conference in November of 2020 outlining progress in the acute management of intracerebral hemorrhage (ICH) over the past 35 years. ICH is the second most common and the deadliest type of stroke for which there is no scientifically proven medical or surgical treatment. Prospective studies from the 1990s onward have demonstrated that most growth of spontaneous ICH occurs within the first 2 to 3 hours and that growth of ICH and resulting volumes of ICH and intraventricular hemorrhage are modifiable factors that can improve outcome. Trials focusing on early treatment of elevated blood pressure have suggested a target systolic blood pressure of 140 mm Hg, but none of the trials were positive by their primary end point. Hemostatic agents to decrease bleeding in spontaneous ICH have included desmopressin, tranexamic acid, and rFVIIa (recombinant factor VIIa) without clear benefit, and platelet infusions which were associated with harm. Hemostatic agents delivered within the first several hours have the greatest impact on growth of ICH and potentially on outcome. No large Phase III surgical ICH trial has been positive by primary end point, but pooled analyses suggest that earlier ICH removal is more likely to be beneficial. Recent trials emphasize maximization of clot removal and minimizing brain injury from the surgical approach. The future of ICH therapy must focus on delivery of medical and surgical therapies as soon as possible if we are to improve outcomes.
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http://dx.doi.org/10.1161/STROKEAHA.121.033484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085038PMC
May 2021

Which Acute Ischemic Stroke Patients Are Fast Progressors?: Results From the ESCAPE Trial Control Arm.

Stroke 2021 May 5;52(5):1847-1850. Epub 2021 Apr 5.

Clinical Neurosciences (J.M.O., M.D.H., A.M.D., B.K.M., A.M., M.G.), University of Calgary, Canada.

Background And Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics.

Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail.

Results: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, =0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], =0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery.

Conclusions: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.
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http://dx.doi.org/10.1161/STROKEAHA.120.032950DOI Listing
May 2021

Neuroimaging of Acute Intracerebral Hemorrhage.

J Clin Med 2021 Mar 5;10(5). Epub 2021 Mar 5.

ASST Valcamonica, UOSD Neurology, Esine (BS), 25040 Brescia, Italy.

Intracerebral hemorrhage (ICH) accounts for 10% to 20% of all strokes worldwide and is associated with high morbidity and mortality. Neuroimaging is clinically important for the rapid diagnosis of ICH and underlying etiologies, but also for identification of ICH expansion, often as-sociated with an increased risk for poor outcome. In this context, rapid assessment of early hema-toma expansion risk is both an opportunity for therapeutic intervention and a potential hazard for hematoma evacuation surgery. In this review, we provide an overview of the current literature surrounding the use of multimodal neuroimaging of ICH for etiological diagnosis, prediction of early hematoma expansion, and prognostication of neurological outcome. Specifically, we discuss standard imaging using computed tomography, the value of different vascular imaging modalities to identify underlying causes and present recent advances in magnetic resonance imaging and computed tomography perfusion.
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http://dx.doi.org/10.3390/jcm10051086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962049PMC
March 2021

Identifying sex-specific differences in the carotid revascularisation literature: findings from a scoping review.

Stroke Vasc Neurol 2021 Mar 29. Epub 2021 Mar 29.

School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Objective: No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female patients. In this scoping review, we aimed to identify all randomised controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularisation, and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female patients.

Design, Setting And Participants: We systematically searched Medline, Embase, Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting, or any revascularisation (endarterectomy or stenting) with medical therapy in patients with symptomatic high-grade (>50%) carotid stenosis.

Results: From 1537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled female patients were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however, there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex.

Conclusions: Only half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited.
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http://dx.doi.org/10.1136/svn-2020-000744DOI Listing
March 2021

Association between insulin resistance and post-ischaemic stroke outcome in patients without diabetes: protocol for a systematic review and meta-analysis.

BMJ Open 2021 03 26;11(3):e044771. Epub 2021 Mar 26.

Neurology, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada.

Introduction: Insulin resistance is an independent risk factor for atherosclerosis, coronary artery disease and ischaemic stroke. Currently, insulin resistance is not usually included in post-stroke risk stratification. This systematic review and meta-analysis intends to determine if available scientific knowledge supports an association between insulin resistance and post-stroke outcomes in patients without diabetes.

Methods And Analysis: The authors will conduct a literature search in Medline, Embase, Web of Science and Cochrane Central. The review will include studies that assess the association between elevated insulin homeostasis model of insulin resistance (HOMA-IR) and post-stroke outcome (functional outcome and recurrent stroke). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines will be used. The primary outcome will be post-stroke functional outcome (Modified Rankin Scale), and the secondary outcome will be recurrent ischaemic stroke. Comparison of outcome will be made between highest and lowest HOMA-IR range (as defined in each article included in this systematic review). Risk of bias will be assessed qualitatively. Meta-analysis will be performed if sufficient homogeneity exists between studies. Heterogeneity of outcomes will be assessed by ².

Ethics And Dissemination: No human or animal subjects or samples were/will be used. The results will be published in a peer-reviewed journal, and will be disseminated at local and international neurology conferences.

Prospero Registration Number: CRD42020173608.
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http://dx.doi.org/10.1136/bmjopen-2020-044771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006852PMC
March 2021

Predicting long-term outcomes in acute intracerebral haemorrhage using delayed prognostication scores.

Stroke Vasc Neurol 2021 Mar 23. Epub 2021 Mar 23.

Department of Medicine, Division of Neurology, Stroke Program, Ottawa Hospital, Ottawa, Ontario, Canada.

Objective: The concept of the 'self-fulfilling prophecy' is well established in intracerebral haemorrhage (ICH). The ability to improve prognostication and prediction of long-term outcomes during the first days of hospitalisation is important in guiding conversations around goals of care. We previously demonstrated that incorporating delayed imaging into various prognostication scores for ICH improves the predictive accuracy of 90-day mortality. However, delayed prognostication scores have not been used to predict long-term functional outcomes beyond 90 days.

Design, Setting And Participants: We analysed data from the ICH Deferoxamine trial to see if delaying the use of prognostication scores to 96 hours after ICH onset will improve performance to predict outcomes at 180 days. 276 patients were included.

Interventions And Measurements: We calculated the original ICH score (oICH), modified-ICH score (MICH), max-ICH score and the FUNC score on presentation (baseline), and on day 4 (delayed). Outcomes assessed were mortality and poor functional outcome in survivors (defined as modified Rankin Scale of 4-5) at 180 days. We generated receiver operating characteristic curves, and measured the area under the curve values (AUC) for mortality and functional outcome. We compared baseline and delayed AUCs with non-parametric methods.

Results: At 180 days, 21 of 276 (7.6%) died. Out of the survivors, 54 of 255 had poor functional outcome (21.2%). The oICH, MICH and max-ICH performed significantly better at predicting 180-day mortality when calculated 4 days later compared with their baseline equivalents ((0.74 vs 0.83, p=0.005), (0.73 vs 0.80, p=0.036), (0.74 vs 0.83, p=0.008), respectively). The delayed calculation of these scores did not significantly improve our accuracy for predicting poor functional outcomes.

Conclusion: Delaying the calculation of prognostication scores in acute ICH until day 4 improved prediction of 6-month mortality but not functional outcomes.

Trial Registration Number: ClinicalTrials.gov Registry (NCT02175225).
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http://dx.doi.org/10.1136/svn-2020-000656DOI Listing
March 2021

Health-Related Quality of Life Among Patients With Acute Ischemic Stroke and Large Vessel Occlusion in the ESCAPE Trial.

Stroke 2021 May 11;52(5):1636-1642. Epub 2021 Mar 11.

Department of Clinical Neurosciences, Department of Radiology, Department of Community Health Sciences (B.K.M., M.D.H), Hotchkiss Brain Institute, University of Calgary, Canada.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.120.033872DOI Listing
May 2021

Intracerebral Hemorrhage Incidence, Mortality, and Association With Oral Anticoagulation Use: A Population Study.

Stroke 2021 May 9;52(5):1673-1681. Epub 2021 Mar 9.

Division of Critical Care, Department of Medicine (S.M.F., S.W.E., K.K.), University of Ottawa, ON, Canada.

Background And Purpose: Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Recent epidemiological data on incidence, mortality, and association with oral anticoagulation are needed.

Methods: Retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (April 1, 2009-March 30, 2019). We captured outcome data using linked health administrative databases. The primary outcome was mortality during hospitalization, as well as at 1 year following ICH.

Results: We included 20 738 patients with ICH. Mean (SD) age was 71.3 (15.1) years, and 52.6% of patients were male. Overall incidence of ICH throughout the study period was 19.1/100 000 person-years and did not markedly change over the study period. In-hospital and 1-year mortality were high (32.4% and 45.4%, respectively). Mortality at 2 years was 49.5%. Only 14.5% of patients were discharged home independently. Over the study period, both in-hospital and 1-year mortality reduced by 10.4% (37.5% to 27.1%, <0.001) and 7.6% (50.0% to 42.4%, <0.001), respectively. Use of oral anticoagulation was associated with both in-hospital mortality (adjusted odds ratio 1.37 [95% CI, 1.26-1.49]) and 1-year mortality (hazard ratio, 1.18 [95% CI, 1.12-1.25]) following ICH.

Conclusions: Both short- and long-term mortality have decreased in the past decade. Most survivors from ICH are likely to be discharged to long-term care. Oral anticoagulation is associated with both short- and long-term mortality following ICH. These findings highlight the devastating nature of ICH, but also identify significant improvement in outcomes over time.
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http://dx.doi.org/10.1161/STROKEAHA.120.032550DOI Listing
May 2021

Advanced consent for acute stroke trials.

Lancet Neurol 2021 03;20(3):170

Department of Medicine, Neurology, Ottawa, ON K1Y 4E9, Canada.

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http://dx.doi.org/10.1016/S1474-4422(21)00029-6DOI Listing
March 2021

Rationalisations for women-only randomised controlled trials in conditions that affect both sexes: a scoping review protocol.

BMJ Open 2021 02 16;11(2):e043370. Epub 2021 Feb 16.

Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Introduction: Women have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care.

Objective: In an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them.

Methodology: This scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics.

Significance: The scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials.

Ethics And Dissemination: Research ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.
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http://dx.doi.org/10.1136/bmjopen-2020-043370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888323PMC
February 2021

Direct oral anticoagulants in treatment of cerebral venous thrombosis: a systematic review.

BMJ Open 2021 02 16;11(2):e040212. Epub 2021 Feb 16.

Department of Medicine, University of Ottawa and The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

Objectives: Current guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarise the published experience of DOAC therapy in CVT.

Data Sources: MEDLINE, Embase and COCHRANE databases up to 18 November 2020.

Eligibility Criteria: All published articles of patients with CVT treated with DOAC were included. Studies without follow-up information were excluded.

Data Extraction And Synthesis: Two independent reviewers screened articles and extracted data. A risk of bias analysis was performed.

Primary And Secondary Outcome Measures: Safety data included mortality, intracranial haemorrhage (ICH) or other adverse events. Efficacy data included recurrent CVT, recanalisation rates and disability by modified Rankin Scales (mRS).

Results: 33 studies met inclusion criteria. One randomised controlled trial, 5 observational cohorts and 27 case series or studies reported 279 patients treated with DOAC for CVT: 41% dabigatran, 47% rivaroxaban, 10% apixaban and 2% edoxaban, in addition to 315 patients treated with standard therapy. The observational cohorts showed a similar risk of death in DOAC and standard therapy arms (RR 2.12, 95% CI 0.29 to 15.59). New ICH was reported in 2 (0.7%) DOAC-treated patients and recurrent CVT occurred in 4 (1.5%). A favourable mRS between 0 and 2 was reported in 94% of DOAC-treated patients, more likely than standard therapy in observational cohorts (RR 1.13, 95% CI 1.02 to 1.25).

Conclusion: The evidence for DOAC use in CVT is limited although suggests sufficient safety and efficacy despite variability in timing and dose of treatment. This systematic review highlights that further rigorous trials are needed to validate these findings and to determine optimal treatment regimens.
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http://dx.doi.org/10.1136/bmjopen-2020-040212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888326PMC
February 2021

Improved Segmentation of the Intracranial and Ventricular Volumes in Populations with Cerebrovascular Lesions and Atrophy Using 3D CNNs.

Neuroinformatics 2021 Feb 1. Epub 2021 Feb 1.

Hurvitz Brain Sciences Program, Sunnybrook Research Institute, University of Toronto, Toronto, Canada.

Successful segmentation of the total intracranial vault (ICV) and ventricles is of critical importance when studying neurodegeneration through neuroimaging. We present iCVMapper and VentMapper, robust algorithms that use a convolutional neural network (CNN) to segment the ICV and ventricles from both single and multi-contrast MRI data. Our models were trained on a large dataset from two multi-site studies (N = 528 subjects for ICV, N = 501 for ventricular segmentation) consisting of older adults with varying degrees of cerebrovascular lesions and atrophy, which pose significant challenges for most segmentation approaches. The models were tested on 238 participants, including subjects with vascular cognitive impairment and high white matter hyperintensity burden. Two of the three test sets came from studies not used in the training dataset. We assessed our algorithms relative to four state-of-the-art ICV extraction methods (MONSTR, BET, Deep Extraction, FreeSurfer, DeepMedic), as well as two ventricular segmentation tools (FreeSurfer, DeepMedic). Our multi-contrast models outperformed other methods across many of the evaluation metrics, with average Dice coefficients of 0.98 and 0.96 for ICV and ventricular segmentation respectively. Both models were also the most time efficient, segmenting the structures in orders of magnitude faster than some of the other available methods. Our networks showed an increased accuracy with the use of a conditional random field (CRF) as a post-processing step. We further validated both segmentation models, highlighting their robustness to images with lower resolution and signal-to-noise ratio, compared to tested techniques. The pipeline and models are available at: https://icvmapp3r.readthedocs.io and https://ventmapp3r.readthedocs.io to enable further investigation of the roles of ICV and ventricles in relation to normal aging and neurodegeneration in large multi-site studies.
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http://dx.doi.org/10.1007/s12021-021-09510-1DOI Listing
February 2021

Noncontrast Computed Tomography Markers as Predictors of Revised Hematoma Expansion in Acute Intracerebral Hemorrhage.

J Am Heart Assoc 2021 02 28;10(3):e018248. Epub 2021 Jan 28.

Department of Neurology The First Affiliated Hospital of Chongqing Medical University Chongqing China.

Background Noncontrast computed tomography (NCCT) markers are the emerging predictors of hematoma expansion in intracerebral hemorrhage. However, the relationship between NCCT markers and the dynamic change of hematoma in parenchymal tissues and the ventricular system remains unclear. Methods and Results We included 314 consecutive patients with intracerebral hemorrhage admitted to our hospital from July 2011 to May 2017. The intracerebral hemorrhage volumes and intraventricular hemorrhage (IVH) volumes were measured using a semiautomated, computer-assisted technique. Revised hematoma expansion (RHE) was defined by incorporating the original definition of hematoma expansion into IVH growth. Receiver operating characteristic curve analysis was used to compare the performance of the NCCT markers in predicting the IVH growth and RHE. Of 314 patients in our study, 61 (19.4%) had IVH growth and 93 (23.9%) had RHE. After adjustment for potential confounding variables, blend sign, black hole sign, island sign, and expansion-prone hematoma could independently predict IVH growth and RHE in the multivariate logistic regression analysis. Expansion-prone hematoma had a higher predictive performance of RHE than any single marker. The diagnostic accuracy of RHE in predicting poor prognosis was significantly higher than that of hematoma expansion. Conclusions The NCCT markers are independently associated with IVH growth and RHE. Furthermore, the expansion-prone hematoma has a higher predictive accuracy for prediction of RHE and poor outcome than any single NCCT marker. These findings may assist in risk stratification of NCCT signs for predicting active bleeding.
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http://dx.doi.org/10.1161/JAHA.120.018248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955436PMC
February 2021

People With Lived Experience at the Centre of Canadian Stroke Best Practice Recommendations: A Model for Guideline Developers.

J Patient Exp 2020 Dec 10;7(6):951-956. Epub 2020 Sep 10.

Heart and Stroke Foundation of Canada, Toronto, Ontario, Canada.

Actively engaging people with lived experience (PWLE) in stroke-related clinical practice guideline development has not been effectively implemented. This pilot project evaluated the feasibility, perceived value, and effectiveness of the Community Consultation and Review Panel (CCRP), a new model to engage PWLE in the writing and review of Canadian Stroke Best Practice Recommendations. Responses to a standardized evaluation tool indicated that participants perceived the CCRP as valued, impactful, effective, and beneficial to stroke care. This project successfully demonstrated that values, experiences, and recommendations of PWLE can be effectively incorporated into guideline content and is applicable to all guideline development processes.
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http://dx.doi.org/10.1177/2374373520956538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786657PMC
December 2020

Is This Contrast? Is This Blood? An Agreement Study on Post-thrombectomy Computed Tomography Scans.

Front Neurol 2020 22;11:593098. Epub 2020 Dec 22.

Ottawa Stroke Program, Department of Medicine (Neurology), University of Ottawa, Ottawa, ON, Canada.

Hemorrhagic transformation after acute ischemic stroke is a dreaded and severe complication of thrombolysis and thrombectomy. However, its detection on post-thrombectomy conventional non-contrast computed tomography (CT) scan can be complicated by the frequent (and sometimes concomitant) presence of contrast, resulting in changes in management. Our objective was to assess the inter- and intra-rater reliability for the detection of blood and/or contrast on day-1 post-thrombectomy CT scans. A total of 18 raters across 3 different specialties independently examined 30 post-thrombectomy CT scans selected from the Aspiration vs. STEnt-Retriever (ASTER) trial. They were asked to judge the presence of blood and contrast. Thirty days later, the same 18 raters again independently judged the 30 scans, in randomized order. Agreement was measured with Fleiss' and Cohen's statistics. Overall agreement on blood and/ or contrast presence was only fair, = 0.291 (95% CI = 0.273-0.309). There were 0 scans with consensus among the 18 readers on the presence of blood and/or contrast. However, intra-rater global agreement across all 18 physicians was relatively high, with a median kappa value of 0.675. This intra-rater consistency was seen across all specialties, regardless of level of training. Physician judgment for the presence of blood and/or contrast on day-1 post-thrombectomy non-contrast CT scan shows limited inter-observer reliability. Advanced imaging modalities may then be warranted for challenging clinical cases.
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http://dx.doi.org/10.3389/fneur.2020.593098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783397PMC
December 2020

Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment: The INTERRSeCT Study.

Stroke 2021 01 15;52(1):203-212. Epub 2020 Dec 15.

Calgary Stroke Program, Hotchkiss Brain Institute, Departments of Clinical Neurosciences and Radiology, Cumming School of Medicine, University of Calgary, Canada (T.O., B.K.M., M.H., M.N., A.A.-S., M.G., M.D.H., M.A., A.M.D.).

Background And Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke.

Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0-3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated.

Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2-3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0-1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0-2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72-20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21-5.51]).

Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.
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http://dx.doi.org/10.1161/STROKEAHA.120.029292DOI Listing
January 2021

Prevalence and the predictive performance of the dynamic CT-angiography spot sign in an observational cohort with intracerebral hemorrhage.

Medicine (Baltimore) 2020 Nov;99(47):e23278

Department of Medical Imaging, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Canada.

The CT-angiography (CTA) spot sign is a predictor of hematoma expansion (HE). We have previously reported on the use of dynamic CTA (dCTA) to detect spot sign, and to study its formation over the acquisition period. In this study, we report the frequency of dCTA spot sign in acute intracerebral hemorrhage, its sensitivity and specificity to predict HE, and explore the rate of contrast extravasation in relation to hematoma growth.We enrolled consecutive patients presenting with primary intracerebral hemorrhage within 4.5 hours. All patients underwent a dCTA protocol acquired over 60 seconds following contrast injection. We calculated frequency of the dCTA spot sign, predictive performance, and rate of contrast extravasation. We compared extravasation rates to the dichotomous definition of significant HE (defined as 6 mL or 33% growth).In 78 eligible patients, dCTA spot sign frequency was 44.9%. In 61 patients available for expansion analysis, sensitivity and specificity of dCTA spot sign was 65.4% and 62.9%, respectively. Contrast extravasation rate did not significantly predict HE (Odds Ratio 15.6 for each mL/min [95% confidence interval 0.30-820.25], P = .17). Correlation between extravasation rate and HE was low (r = 0.297, P= .11). Patients with significant HE had a higher rate of extravasation as compared to those without (0.12 mL/min vs 0.04 mL/min, P = .03).Dynamic CTA results in a higher frequency of spot sign positivity, but with modest sensitivity and specificity to predict expansion. Extravasation rate is likely related to HE, but a single measurement may be insufficient to predict the magnitude of expansion.
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http://dx.doi.org/10.1097/MD.0000000000023278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676581PMC
November 2020

Early Recanalization With Alteplase in Stroke Because of Large Vessel Occlusion in the ESCAPE Trial.

Stroke 2021 01 20;52(1):304-307. Epub 2020 Nov 20.

Department of Clinical Neurosciences (J.M.O., N.S., M.A.A., B.K.M., A.M.D., M.G., M.D.H.), University of Calgary, Canada.

Background And Purpose: Quantitating the effect of intravenous alteplase on the technical outcome of early recanalization of large vessel occlusions aids understanding. We report the prevalence of early recanalization in patients with stroke because of large vessel occlusion treated with and without intravenous alteplase and endovascular thrombectomy, and its association with clinical outcome.

Methods: Patients with acute ischemic stroke with large vessel occlusion from the ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times Trial) were included in this post hoc analysis. Outcomes of interest were the prevalence of early recanalization (1) and good outcome (2), defined as modified Rankin Scale score of 0 to 2 at 90 days.

Results: Among 147 patients who did not receive endovascular thrombectomy, early recanalization occurred in 4/30 (13.3%) patients without and 48/117 (41.0%) patients with intravenous alteplase (adjusted risk ratios, 3.2 [95% CI, 1.2-8.1]). Good outcome was achieved by 34/116 (29.3%) of patients who received intravenous alteplase versus 10/29 (34.5%) who did not receive alteplase (adjusted risk ratios, 1.0 [95% CI, 0.6-1.5) and by 20/52 (38.5%) patients with versus 24/93 (25.8%) without early recanalization (adjusted risk ratios, 1.9 [95% CI, 1.2-2.9]).

Conclusions: Early recanalization was confirmed as a strong predictor of good outcome in patients who did not undergo endovascular thrombectomy and was improved with intravenous alteplase, yet a majority of patients (59.0%) did not achieve early reperfusion. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01778335.
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http://dx.doi.org/10.1161/STROKEAHA.120.031591DOI Listing
January 2021

Canadian stroke best practice recommendations: , 7th Edition Update 2020.

Int J Stroke 2021 04 11;16(3):321-341. Epub 2020 Nov 11.

Department of Neurology, Universite de Montreal, Montreal, Canada.

Spontaneous intracerebral hemorrhage is a particularly devastating type of stroke with greater morbidity and mortality compared with ischemic stroke and can account for half or more of all deaths from stroke. The seventh update of the includes a new stand-alone module on intracerebral hemorrhage, with a focus on elements of care that are unique or affect persons disproportionately relative to ischemic stroke. Prior to this edition, intracerebral hemorrhage was included in the Acute Stroke Management module and was limited to its management during the first 12 h. With the growing evidence on intracerebral hemorrhage, a separate module focused on this topic across the care continuum was added. In addition to topics related to initial clinical management, neuroimaging, blood pressure management, and surgical management, new sections have been introduced addressing topics surrounding inpatient complications such as venous thromboembolism, seizure management, and increased intracranial pressure, rehabilitation as well as issues related to secondary management including lifestyle management, maintaining a normal blood pressure and antithrombotic therapy, are addressed. The () are intended to provide up-to-date evidence-based guidelines for the prevention and management of stroke and to promote optimal recovery and reintegration for people who have experienced stroke, including patients, families, and informal caregivers.
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http://dx.doi.org/10.1177/1747493020968424DOI Listing
April 2021

Revised intracerebral hemorrhage expansion definitions: Relationship with care limitations.

Int J Stroke 2020 Nov 2:1747493020967255. Epub 2020 Nov 2.

Ottawa Stroke Program, Department of Medicine (Neurology), University of Ottawa and Ottawa Hospital Research Institute, Ottawa, ON, Canada.

Background: Hematoma expansion is an important therapeutic target in intracerebral hemorrhage. Recently proposed hematoma expansion definitions have not been validated, and no previous definition has accounted for withdrawal of care.

Aims: To externally validate revised definitions of hematoma expansion that incorporate intraventricular hemorrhage, and to test their validity in the context of withdrawal of care.

Methods: We analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II trial, comparing revised definitions of hematoma expansion incorporating intraventricular hemorrhage expansion to the conventional definition of "≥6 mL or ≥33%." Primary outcome was modified Rankin Scale of 4-6 at 90 days. We calculated the incidence, sensitivity, specificity, positive and negative predictive values, and statistic for all definitions of hematoma expansion. Definitions were compared using nonparametric methods. Secondary analyses were performed after removing patients with withdrawal of care.

Results: Primary analysis included 948 patients. Using the conventional definition, the sensitivity was 37.1% and specificity was 83.2% for the primary outcome. Sensitivity improved with all three revised definitions (53.3%, 48.7%, and 45.3%, respectively), with minimal change to specificity (78.4%, 80.5%, and 81.0%, respectively). The greatest improvement was seen with the definition "≥6 mL or ≥33% or any intraventricular hemorrhage," with increased -statistic from 60.2% to 65.9% ( < 0.001). Secondary analysis excluded 46 participants who experienced withdrawal of care. The revised definitions similarly outperformed the conventional definition in this population, with the greatest improvement in -statistic using "≥6 mL or ≥33% or any intraventricular hemorrhage" (58.1% vs. 64.1%,  < 0.001).

Conclusions: Revised hematoma expansion definitions incorporating intraventricular hemorrhage expansion outperformed conventional definitions for predicting poor outcome, even after accounting for care limitations.
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http://dx.doi.org/10.1177/1747493020967255DOI Listing
November 2020
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