Thalia Field
University of British Columbia, Medicine, Neurology, Faculty Member
- Stroke Neurologist, Vancouver Stroke ProgramAssistant Professor, University of British Columbia Faculty of Medicineedit
Background and Purpose: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and... more
Background and Purpose: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. Methods: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. Results: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63–79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2–4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6–9] versus 6 [4–9]), similar favorable thrombus permeability (residual flow grades I–II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11–13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26–60.13]) were associated with successful recanalization among mild patients. Conclusions: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.
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Background Health state utility values are commonly used to provide summary measures of health‐related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies... more
Background Health state utility values are commonly used to provide summary measures of health‐related quality of life in studies of stroke. Contemporaneous summaries are needed as a benchmark to contextualize future observational studies and inform the effectiveness of interventions aimed at improving post‐stroke quality of life. Methods and Results We conducted a systematic search of the literature using Medline, EMBASE, and Web of Science from January 1995 until October 2020 using search terms for stroke, health‐related quality of life, and indirect health utility metrics. We calculated pooled estimates of health utility values for EQ‐5D‐3L, EQ‐5D‐5L, AQoL, HUI2, HUI3, 15D, and SF‐6D using random effects models. For the EQ‐5D‐3L we conducted stratified meta‐analyses and meta‐regression by key subgroups. We screened 14 251 abstracts and 111 studies met our inclusion criteria (sample size range 11 to 12 447). EQ‐5D‐3L was reported in 78% of studies (study n=87; patient n=56 976). The pooled estimate for EQ‐5D‐3L at ≥3 months following stroke was 0.65 (95% CI, 0.63–0.67), which was ≈20% below population norms. There was high heterogeneity (I 2 >90%) between studies, and estimates differed by study size, case definition of stroke, and country of study. Women, older individuals, those with hemorrhagic stroke, and patients prior to discharge had lower pooled EQ‐5D‐3L estimates. Conclusions Pooled estimates of health utility for stroke survivors were substantially below population averages. We provide reference values for health utility in stroke to support future clinical and economic studies and identify subgroups with lower healthy utility. Registration URL: https://www.crd.york.ac.uk/prospero/ . Unique Identifier: CRD42020215942.
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Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of... more
Women, especially following menopause, are known to have worse outcomes following acute ischemic stroke. One primary postulated biological mechanism for worse outcomes in older women is a reduction in the vasculoprotective effects of estrogen. Using the INTERRseCT cohort, a multicentre international observational cohort studying recanalization in acute ischemic stroke, we explored the effects of sex, and modifying effects of age, on neuroradiological predictors of recanalization including robustness of leptomeningeal collaterals, thrombus burden and thrombus permeability. Ordinal regression analyses were used to examine the relationship between sex and each of the neuroradiological markers. Further, we explored both multiplicative and additive interactions between age and sex. All patients (n = 575) from INTERRseCT were included. Mean age was 70.2 years (SD: 13.1) and 48.5% were women. In the unadjusted model, female sex was associated with better collaterals (OR 1.37, 95% CIs: 1.01–1.85), however this relationship was not significant after adjusting for age and relevant comorbidities. There were no significant interactions between age and sex. In a large prospective international cohort, we found no association between sex and radiological predictors of recanalization including leptomeningeal collaterals, thrombus permeability and thrombus burden.
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BackgroundHomeless or precariously housed individuals live with poor health and experience premature mortality compared with the general population, yet little is known about age-related brain changes among these individuals. We evaluated... more
BackgroundHomeless or precariously housed individuals live with poor health and experience premature mortality compared with the general population, yet little is known about age-related brain changes among these individuals. We evaluated whether MRI measures of brain structure are differentially associated with age and selected risk factors among individuals who are homeless or precariously housed compared with a general population sample.MethodsWe compared T1-weighted and diffusion tensor imaging measures of brain macrostructure and white matter microstructure in a well-characterised sample of 312 precariously housed participants with a publicly available dataset of 382 participants recruited from the general population. We used piecewise and multiple linear regression to examine differential associations between MRI measures and between the samples, and to explore associations with risk factors in the precariously housed sample.ResultsCompared with the general population sample, ...
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Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after... more
Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0–2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years...
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ABSTRACT: The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need... more
ABSTRACT: The National Institutes of Health Toolbox-Cognition Battery (NIHTB-CB) is a tablet-based cognitive assessment intended for individuals with neurological diseases of all ages. NIHTB-CB practice effects (PEs), however, need clarification if this measure is used to track longitudinal change. We explored the test–retest PEs on NIHTB-CB performance at 3 months in young healthy adults (n = 22). We examined corrected T-scores normalized for demographic factors and calculated PEs using Cohen’s d. There were significant PEs for all NIHTB-CB composite scores and on 4/7 subtests. This work suggests the need to further assess NIHTB-CB PEs as this may affect the interpretation of study results incorporating this battery.
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ObjectiveCerebral venous thrombosis (CVT) caused by vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus‐based severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines. In March... more
ObjectiveCerebral venous thrombosis (CVT) caused by vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus‐based severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non‐heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.MethodsWe used data from an international prospective registry of patients with CVT after the adenovirus‐based SARS‐CoV‐2 vaccination. We analyzed possible, probable, or definite VITT‐CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.ResultsNinety‐nine patients with VITT‐CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 2...
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Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical... more
Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) adenoviral vector vaccination. In British Columbia (BC), Canada, a provincial clinical care pathway was developed to guide clinicians in evaluating for VITT among patients who present with thrombocytopenia or thrombosis symptoms within 4 to 28 days after adenoviral vector vaccine exposure. All patients had enzyme-linked immunosorbent assay (ELISA) testing for platelet factor 4 (PF4) antibodies, and all cases with positive PF4-ELISA or d-dimer levels ≥2.0 mg/L fibrinogen equivalent units (FEU) had further testing for platelet-activating PF4 antibodies using a modified serotonin release assay (SRA). Between 1 May and 30 June 2021, 37% of 68 patients investigated for VITT had thrombosis, but only 3 had VITT confirmed by PF4-ELISA and SRA. Platelet counts, d-dimer levels, and ELISA optical density values were significantly different between ...
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Background and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality... more
Background and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year.Methods We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020).Results There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observe...
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Background Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment in older adults, due to its... more
Background Subcortical ischemic vascular cognitive impairment (SIVCI) is the most common form of vascular cognitive impairment. Importantly, SIVCI is considered the most treatable form of cognitive impairment in older adults, due to its modifiable risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia. Exercise training is a promising intervention to delay the progression of SIVCI, as it actively targets these cardiometabolic risk factors. Despite the demonstrated benefits of resistance training on cognitive function and emerging evidence suggesting resistance training may reduce the progression of white matter hyperintensities (WMHs), research on SIVCI has predominantly focused on the use of aerobic exercise. Thus, the primary aim of this proof-of-concept randomized controlled trial is to investigate the efficacy of a 12-month, twice-weekly progressive resistance training program on cognitive function and WMH progression in adults with SIVCI. We will also as...
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Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the... more
Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atheroscler...
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Objective The purpose of this study was to provide contemporary estimates of the prevalence of lower extremity motor impairment and walking limitation after first-ever stroke and to characterize the predictive nature of early walking... more
Objective The purpose of this study was to provide contemporary estimates of the prevalence of lower extremity motor impairment and walking limitation after first-ever stroke and to characterize the predictive nature of early walking ability for being discharged home after acute hospitalization. Methods In this cohort study, data were collected from a metropolitan acute care hospital in Canada at admission for 487 adults with first-ever acute ischemic or hemorrhagic stroke. Lower extremity motor impairment and walking limitation were measured using the National Institutes of Health Stroke Scale and AlphaFIM, respectively. Parallel multivariable logistic regression models were built to predict discharge home after acute hospitalization compared with further hospitalization. Results For patients surviving a first-ever stroke, 44.1% presented with some degree of lower extremity motor impairment and 46.0% were unable to walk. In a multivariable model built around a binary classification...
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Background Artificial intelligence (AI) is no longer a futuristic concept; it is increasingly being integrated into health care. As studies on attitudes toward AI have primarily focused on physicians, there is a need to assess the... more
Background Artificial intelligence (AI) is no longer a futuristic concept; it is increasingly being integrated into health care. As studies on attitudes toward AI have primarily focused on physicians, there is a need to assess the perspectives of students across health care disciplines to inform future curriculum development. Objective This study aims to explore and identify gaps in the knowledge that Canadian health care students have regarding AI, capture how health care students in different fields differ in their knowledge and perspectives on AI, and present student-identified ways that AI literacy may be incorporated into the health care curriculum. Methods The survey was developed from a narrative literature review of topics in attitudinal surveys on AI. The final survey comprised 15 items, including multiple-choice questions, pick-group-rank questions, 11-point Likert scale items, slider scale questions, and narrative questions. We used snowball and convenience sampling metho...
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ABSTRACTImportanceHomeless or precariously housed individuals live with poor health and experience premature mortality compared to the general population. With an increasing average age among this demographic, syndromes associated with... more
ABSTRACTImportanceHomeless or precariously housed individuals live with poor health and experience premature mortality compared to the general population. With an increasing average age among this demographic, syndromes associated with neurogenerative disease are also increasing. Quantitative MRI measures may help define the roles of age and risk factors for poor brain health among these individuals.ObjectiveTo evaluate whether MRI measures of brain structure are differentially associated with age and selected risk factors among individuals who are homeless or precariously housed compared to a general population sample.Design, setting, and participantsCross sectional comparison of baseline data from 312 community-based, precariously housed participants with a publicly available dataset of 382 participants recruited from the general population.Exposure(s)The primary exposure was housing status (precariously housed vs general population). Risk factors in the precariously housed sample...
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BACKGROUND Speech data for medical research can be collected non-invasively and in large volumes. Speech analysis has shown promise in diagnosing neurodegenerative disease. To effectively leverage speech data, transcription is important... more
BACKGROUND Speech data for medical research can be collected non-invasively and in large volumes. Speech analysis has shown promise in diagnosing neurodegenerative disease. To effectively leverage speech data, transcription is important as there is valuable information contained in lexical content. Manual transcription, while highly accurate, limits potential scalability and cost savings associated with language-based screening. OBJECTIVE To better understand the use of automatic transcription for classification of neurodegenerative disease (Alzheimer’s Disease [AD], mild cognitive impairment [MCI] or subjective memory complaints [SMC] versus healthy controls), we compared automatically generated transcripts against transcripts that went through manual correction. METHODS We recruited individuals from a memory clinic (“patients”) with a diagnosis of mild-moderate AD, (n=44), MCI (n=20), SMC (n=8) and healthy controls living in the community (n=77). Participants were asked to describ...
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Background Transition from International Classification of Diseases ( ICD ) Ninth and Tenth Revisions ( ICD‐9 and ICD‐10 ) for hospital discharge data was mandated for US hospitals on October 1, 2015. We examined the volume of patients... more
Background Transition from International Classification of Diseases ( ICD ) Ninth and Tenth Revisions ( ICD‐9 and ICD‐10 ) for hospital discharge data was mandated for US hospitals on October 1, 2015. We examined the volume of patients receiving thrombolysis in ischemic stroke (IS) identified using ICD codes within this transition period in the 2015 to 2016 National Inpatient Sample, a weighted 20% sample of all inpatient US hospital discharges. Methods and Results During the ICD‐10 period, 2 case identification strategies were used. Codes for IS were combined with: (1) only the ICD‐10 code for thrombolytic given into a peripheral vein and (2) all new ICD‐10 codes mapped to the ICD‐9 code for all thrombolysis. On visual inspection there was an obvious discontinuity in the volume of patients with IS treated with IV thrombolysis corresponding to 3 time periods: ICD‐9 (study period 1), transition (period 2), and ICD‐10 (period 3). With Strategy 1, analysis using a linear spline with 2 ...
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Background and Purpose— The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral... more
Background and Purpose— The use of vitamin K antagonists (VKAs), the cornerstone treatment for stroke prevention in patients with atrial fibrillation, is limited by the perceived risk of serious bleeding in Asia. Non-VKA oral anticoagulants (NOACs) are safer alternatives. Here, we evaluate performance differences of NOACs between Asians and non-Asians. Methods— We compared efficacy and safety of NOACs between patients enrolled in Asian and non-Asian countries using aggregative data from phase III clinical trials. The odds ratios (ORs [95% confidence interval]) were calculated by a random effects model. Results— Comparing with VKAs, standard-dose NOACs reduced stroke or systemic embolism (OR=0.65 [0.52–0.83] versus 0.85 [0.77–0.93], P interaction= 0.045) more in Asians than in non-Asians and were safer in Asians than in non-Asians about major bleeding (OR=0.57 [0.44–0.74] versus 0.89 [0.76–1.04], P interaction=0.004), hemorrhagic stroke (OR=0.32 [0.19–0.52] versus 0.56 [0.44–0.70], P...
Research Interests: Medicine, Stroke, Internal Medicine, Atrial Fibrillation, Two Stroke Engine, and 9 moreClinical Sciences, Public health systems and services research, Odds ratio, Neurosciences, Confidence Interval, Gastrointestinal bleeding, Edoxaban, Vitamin K Antagonist, and Cardiovascular medicine and haematology
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In high-income countries, cerebral venous thrombosis (CVT) has been generally regarded as a rare cause of stroke with a good overall prognosis. The rarity of the disease has made it difficult to study in clinical trials, and current... more
In high-income countries, cerebral venous thrombosis (CVT) has been generally regarded as a rare cause of stroke with a good overall prognosis. The rarity of the disease has made it difficult to study in clinical trials, and current treatment guidelines for CVT are consensus based. Significant equipoise exists around multiple treatment decisions—choice of anticoagulant, duration of therapy, role of neuroimaging in therapeutic decision-making, and role for heroic therapies. Therapeutic strategies for CVT should be better refined, and there are multiple recent and ongoing trials aimed at addressing the challenge of how to best treat this disease. However, in identifying the best evidence-based treatment strategies for CVT, we will also need to identify the best primary outcomes to evaluate these therapies. Estimates from high-income European nations and Australia estimate that CVT affects ≈0.5 to 1/100 000 people per year in the general population, though the disease may remain underdiagnosed if clinical suspicion or overt findings on nonvascular neuroimaging do not prompt diagnostic venography. Observational studies report favorable functional outcomes, with 85% to 90% of patients achieving a modified Rankin Scale (mRS) score of 0 to 1 at 3 to 6 months after diagnosis. Even for those who achieve a favorable mRS outcome, CVT can remain a disabling condition. Existing long-term follow-up studies suggest that up to 60% of these generally well, young individuals have ongoing neuropsychiatric complaints, headache, fatigue, and cognitive issues, with one-quarter being unable to return to work. Further, anticoagulation with vitamin K antagonists (VKAs), the standard of care for most CVT patients, negatively impacts quality of life in younger adults with venous thromboembolism (VTE), particularly during the first few months of therapy. Typical frustrations with VKA use include disruptions to work and travel related to international normalized ratio monitoring, alterations in diet and alcohol consumption, and limitations to social activities. Those who have pursued clinical trials for therapy of CVT have chosen primary outcomes—recurrent VTE, major bleeding, and mRS at day 180—in line with therapeutic trials for more common forms of VTE and more disabling forms of stroke. However, this strategy perpetuates uncertainty for treating clinicians. Rates of recurrent VTE, major bleeding, death, and dependence in CVT are low. The rarity of CVT, compounded by the rarity of these outcomes, leaves trials underpowered. One could argue that in a trial of experimental therapy for CVT, even with an underpowered study, one would be able to exclude an approach with a highly unacceptable safety or tolerability profile. However, a focus on more common patient-centered outcomes may help to define future therapies that are acceptably safe, focused on patient needs, and supported by high-quality trial data.
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Background: Recent reported population-based rates of cerebral venous thrombosis (CVT) are higher than in older studies, though the context of these diagnoses is not well-defined. To better understand these trends, we examined the... more
Background: Recent reported population-based rates of cerebral venous thrombosis (CVT) are higher than in older studies, though the context of these diagnoses is not well-defined. To better understand these trends, we examined the accuracy of administrative codes ( ICD-10 ) for CVT in different clinical scenarios. Methods: Cases of CVT presenting to a tertiary center between 2008-2018 were identified in two ways: free text search through all hospital electronic radiology reports regardless of modality and body part and any ICD-10 discharge codes (see Table 1). Electronic medical records were reviewed to verify diagnoses of CVT and their clinical context (Figure 1) to calculated Positive Predictive Value (PPV) of ICD-10 codes. Additionally, sensitivities of ICD-10 codes were calculated against all CVTs identified using either searches that were verified on chart review as the gold standard. Results: There were 289 confirmed cases: 239 new diagnoses, 204 of which were acute events. Only 75 cases (37%) were new, symptomatic CVTs not provoked by trauma or structural processes. Sensitivity and PPV for ICD-10 codes depending on clinical context is reported in Table 1. Conclusion: The majority of CVT identified at our institution were incidentally diagnosed in context of intracranial processes such as trauma, surgery, infection, or masses; 37% were symptomatic, non-structural incident diagnoses. Our findings have implications in interpreting CVT rates identified through administrative data, as the management and prognosis of CVT may differ based on clinical context.
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We read with interest the CMAJ Analysis by Aubin and colleagues,[1][1] which identified issues in developing and measuring the impact of patient-oriented research. We are studying cerebral venous thrombosis (CVT), an uncommon cause of... more
We read with interest the CMAJ Analysis by Aubin and colleagues,[1][1] which identified issues in developing and measuring the impact of patient-oriented research. We are studying cerebral venous thrombosis (CVT), an uncommon cause of stroke, in a national trial (Study of rivaroxaban in CeREbral
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Introduction: The previously published cerebral SVD Score is a four-point rating scale based on the four cardinal MRI markers of SVD: moderate-severe white matter hyperintensities, , lacune(s), moderate-severe enlarged perivascular spaces... more
Introduction: The previously published cerebral SVD Score is a four-point rating scale based on the four cardinal MRI markers of SVD: moderate-severe white matter hyperintensities, , lacune(s), moderate-severe enlarged perivascular spaces (PVS), and microbleed(s). We evaluated the score’s ability to predict recurrent stroke in the Secondary Prevention of Small Subcortical Strokes (SPS3) Trial. Methods: One point each was awarded for these 4 MRI findings: max periventricular Fazekas score = 3 and/or max subcortical Fazekas score > 2; >1 cerebral microbleed 2 (i.e. > 11 PVS unilaterally); > 1 old lacune (3-15 mm) on FLAIR/T1. Annualized rates of recurrent stroke were computed assuming a Poisson model, and c-statistics were calculated for the SVD score model and for two other previously published SPS3 derived models. Results: Of 3020 participants, 1137 had complete data available for SVD scoring. Prevalence of SVD scores 0, 1, 2, 3, and 4 were 19% (n=219), 29% (n=325), 24% (n=277), 18% (n=200), and 10% (n=116). PVS (55%) were most common, followed by moderate-severe white matter hyperintensities (45), lacunes (41), and microbleeds (30). Recurrent stroke rates did not strictly increase with increasing SVD score, i.e. rates were 2.4%/pt-yr (95% CI 1.5, 3.9), 1.4 (0.8, 2.3), 2.0 (1.3, 3.2), 3.8 (2.5, 5.7), and 3.2 (1.8, 5.6) respectively. When SVD scores of 0-2 vs. 3-4 were grouped and compared with two other models for predicting recurrent stroke in this cohort, the SVD score model did not outperform. (Table) Conclusions: SVD score features were very common in the SPS3 cohort. Higher (3-4) vs. lower (0-2) SVD scores predicted recurrent stroke with similar predictive ability to models including clinical risk factors only +/- fewer MRI features. Further testing of the SVD score is warranted.
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Background: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and... more
Background: Infarct in a new territory (INT) is a known complication of endovascular stroke therapy. We assessed the incidence of INT, outcomes after INT, and the impact of concurrent treatments with intravenous thrombolysis and nerinetide. Methods: Data are from ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide [NA-1] in Subjects Undergoing Endovascular Thrombectomy for Stroke), a multicenter, international randomized study that assessed the efficacy of intravenous nerinetide in subjects with acute ischemic stroke who underwent endovascular thrombectomy within 12 hours from onset. Concurrent treatment and outcomes were collected as part of the trial protocol. INTs were identified on core lab imaging review of follow-up brain imaging and defined by the presence of infarct in a new vascular territory, outside the baseline target occlusion(s) on follow-up brain imaging (computed tomography or magnetic resonance imaging). INTs were classified by maximum diameter (<2, 2–20, and >20 mm), number, and location. The association between INT and clinical outcomes (modified Rankin Scale and death) was assessed using standard descriptive techniques and adjusted estimates of effect were derived from Poisson regression models. Results: Among 1092 patients, 103 had INT (9.3%, median age 69.5 years, 49.5% females). There were no differences in baseline characteristics between those with versus without INT. Most INTs (91/103, 88.3%) were not associated with visible occlusions on angiography and 39 out of 103 (37.8%) were >20 mm in maximal diameter. The most common INT territory was the anterior cerebral artery (27.8%). Almost half of the INTs were multiple (46 subjects, 43.5%, range, 2–12). INT was associated with poorer outcomes as compared to no INT on the primary outcome of modified Rankin Scale score of 0 to 2 at 90 days (adjusted risk ratio, 0.71 [95% CI, 0.57–0.89]). Infarct volume in those with INT was greater by a median of 21 cc compared with those without, and there was a greater risk of death as compared to patients with no INT (adjusted risk ratio, 2.15 [95% CI, 1.48–3.13]). Conclusions: Infarcts in a new territory are common in individuals undergoing endovascular thrombectomy for acute ischemic stroke and are associated with poorer outcomes. Optimal therapeutic approaches, including technical strategies, to reduce INT represent a new target for incremental quality improvement of endovascular thrombectomy. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02930018.
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Background: Studying the baseline incidence of cerebral venous thrombosis (CVT) prior to COVID-19 and the limitations of how this has been previously reported in the literature will help improve understanding of this disease and how risks... more
Background: Studying the baseline incidence of cerebral venous thrombosis (CVT) prior to COVID-19 and the limitations of how this has been previously reported in the literature will help improve understanding of this disease and how risks may have changed in the post-COVID era. Methods: We examined CVT incidence using linked administrative data in British Columbia, Canada (population 5.2 million). To contextualize our findings, we also examined CVT incidence in the published literature and searched MEDLINE and EMBASE for article titles and abstracts up to Nov 2, 2021 on CVT incidence in adults. We performed abstract screening and full-text review prior to data extraction and explored associations between CVT incidence and year of study, geographic location, and study quality with meta-analyses and meta-regression. A random-effects restricted maximum likelihood model was used. Publication bias was assessed using the Egger tests and using visual inspection of the funnel plot for symmetry. Results: There were 554 unique CVT cases (mean age 50.9 years, 55.4% women) in British Columbia from 2000 to 2017; overall annual incidence was 8.7 (95%CI‚ 8.0–9.4) per million. Incidence increased over time in men across the entire study period, and from 2011 to 2017 in women. We identified 22 other studies on CVT incidence before 2020 (21/23 total studies included in meta-analysis). Annual incidence overall was 12.1 (95% CI‚ 9.9–14.3) per million with significant between-study heterogeneity (I 2 98.8%, Qp-value<0.001). There were no significant associations on meta-regression between incidence and study year, study quality score, or gross national income per capita of the study country. Visual inspection of the funnel plot and a significant Egger test (z=2.8, P <0.01) suggested possible publication bias. Conclusions: Incidence of CVT in Canadian data increased over time but remained lower than in other population-based studies. Significant heterogeneity exists in the literature, which may be subject to publication bias.
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Abstract Patterns of practice for management of cerebral venous thrombosis in Canada are unknown. We surveyed Canadian neurologists and hematologists regarding anticoagulation in cerebral venous thrombosis. The response rate was 28%, with... more
Abstract Patterns of practice for management of cerebral venous thrombosis in Canada are unknown. We surveyed Canadian neurologists and hematologists regarding anticoagulation in cerebral venous thrombosis. The response rate was 28%, with 27 neurologists and 20 hematologists responding. We found that choice of first-line initial anticoagulation differed significantly between neurologists and hematologists, with 89% of neurologists favouring unfractionated heparin and hematologists’ preference split between unfractionated heparin (50%) and low-molecular-weight heparin (50%). Differences in patterns of practice likely reflect clinical equipoise. RÉSUMÉ Stratégie antithrombotique dans le traitement de la thrombose veineuse cérébrale : différences entre les neurologues et les hématologues qui ont répondu à une enquête canadienne. Les modes de pratique concernant le traitement de la thrombose veineuse cérébrale au Canada ne sont pas connus. Nous avons procédé à une enquête auprès des neurologues et des hématologues canadiens concernant l’anticoagulation dans le traitement de la thrombose veineuse cérébrale. Vingt-sept neurologues et 20 hématologues ont répondu à l’enquête, soit 28% des spécialistes pressentis. Nous avons constaté que le choix de l’anticoagulant comme traitement initial de première ligne était significativement différent entre les neurologues et les hématologues : 89% des neurologues préféraient administrer de l’héparine non fractionnée alors que 50% des hématologues préféraient administrer de l’héparine non fractionnée et 50% préféraient administrer de l’héparine de faible poids moléculaire. Les différences entre ces modes de pratique reflètent vraisemblablement leur équilibre clinique.
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BackgroundIncomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are... more
BackgroundIncomplete reperfusion (IR) after mechanical thrombectomy (MT) can be a consequence of residual occlusion, no-reflow phenomenon, or collateral counterpressure. Data on the impact of these phenomena on clinical outcome are limited.MethodsPatients from the ESCAPE-NA1 trial with IR (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b) were compared with those with complete or near-complete reperfusion (eTICI 2c-3) on the final angiography run. Final runs were assessed for (a) an MT-accessible occlusion, or (b) a non-MT-accessible occlusion pattern. The primary clinical outcome was modified Rankin Scale (mRS) 0–2 at 90 days. Our imaging outcome was infarction in IR territory on follow-up imaging. Unadjusted and adjusted incidence rate ratios (aIRR) with 95% confidence intervals (95% CI) were obtained.ResultsOf 1105 patients, 443 (40.1%) with IR and 506 (46.1%) with complete or near-complete reperfusion were included. An MT-accessible occlusion was identified in 147/443 patients (33.2%) and a non-MT-accessible occlusion in 296/443 (66.8%). As compared with patients with near-complete/complete reperfusion, patients with IR had significantly lower chances of achieving mRS 0–2 at 90 days (aIRR 0.82, 95% CI 0.74 to 0.91). Rates of mRS 0–2 were lower in the MT-accessible occlusion group as compared with the non-MT-accessible occlusion pattern group (aIRR 0.71, 95% CI 0.60 to 0.83, and aIRR 0.89, 95% CI 0.81 to 0.98, respectively). More patients with MT-accessible occlusion patterns developed infarcts in the non-reperfused territory as compared with patients with non-MT occlusion patterns (68.7% vs 46.3%).ConclusionIR was associated with worse clinical outcomes than near-complete/complete reperfusion. Two-thirds of our patients with IR had non-MT-accessible occlusion patterns which were associated with better clinical and imaging outcomes compared with those with MT-accessible occlusion patterns.
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Introduction: Early anticoagulation after acute ischemic stroke is usually avoided due to the risk of hemorrhagic transformation (HT). We aimed to assess the rate of radiological HT associated with direct oral anticoagulant (DOAC)... more
Introduction: Early anticoagulation after acute ischemic stroke is usually avoided due to the risk of hemorrhagic transformation (HT). We aimed to assess the rate of radiological HT associated with direct oral anticoagulant (DOAC) initiation within 48 hours vs. > 48 hours in the post-stroke period. Methods: A pooled analysis of five studies of DOAC initiation within 14 days of ischemic stroke onset was conducted. The primary endpoint was incident radiographic HT on follow-up imaging. Secondary endpoints included symptomatic HT, new parenchymal hemorrhage (PH1 or asymptomatic PH2), recurrent systemic events, systemic hemorrhagic complications, mortality within the study period, final modified Rankin Scale score. The results were reported as odds ratio (OR) with 95% confidence interval (CI). Results: A total of 468 patients were enrolled. Median infarct volume was 1.35 (0-7.5) ml, and National Institutes of Health Stroke Scale was 1 (0-3). Incident radiographic HT was seen on follow-up scan in 29 patients. DOAC initiation within 48 hours from index event onset was not associated with incident HT (adjusted OR 0.67, [0.31 - 1.50] P =0.34). No patients developed symptomatic HT. Conversely, 25 patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating DOAC within 48 hours of onset was not associated with a reduction in the risk of recurrent ischemic events (OR 0.47, [0.19 - 1.20] P =0.12). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR=6.8, [2.95 - 15.63], p<0.0001). Conclusions: Early DOAC initiation after stroke was not associated with increased incident HT risk. Recurrent ischemic events were common and associated with poor outcomes. These data may be useful for estimating outcome rates and sample size calculations in future trials of early versus late DOAC initiation after AF-related stroke.
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BackgroundDetermining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication.ObjectiveTo estimate infarct progression rate in patients with AIS with... more
BackgroundDetermining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication.ObjectiveTo estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome.MethodsData are from the ESCAPE-NA1 Trial. Patients with AIS with time from last known well to randomization <6 hours and near-complete reperfusion following endovascular treatment were included. Infarct growth rate (mL/h) was estimated by dividing 24 hour infarct volume (measured by non-contrast CT or diffusion-weighted magnetic resonance imaging) by time from last known well to reperfusion. Multivariable linear regression was used to assess the association of patient baseline variables with log-transformed infarct progression rate. The association of infarct progression rate and good outcome (modified Rankin Scale score 0–2) was determined using multivariable logistic regression.ResultsFour hundred and nine patients were included in the study. Median infarct progression rate was 4.74 mL/h (IQR 1.25–14.84). Collateral status (β: −0.81 (95% CI −1.20 to −0.41)), Alberta Stroke Program Early CT Score (ASPECTS, β: −0.34 (95% CI −0.46 to −0.23)), blood glucose(β: 0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (β: 0.07 (95% CI 0.04 to 0.10)) were associated with log-transformed infarct progression rate. Clinical and imaging baseline variables explained 23% of the variance in infarct progression rate. Infarct progression rate was significantly associated with good outcome (aOR per 1 mL/h increase: 0.96 (95% CI 0.95 to 0.98)).ConclusionIn this sample of patients presenting within the early time window with LVO and near-complete recanalization, infarct progression rate was significantly associated with good outcome. A significant association between ASPECTS, collateral status, blood glucose, and NIHSS score was observed, but baseline imaging and clinical characteristics explained only a small proportion of the interindividual variance. More research on measurable factors affecting infarct growth is needed.
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In high-income countries, cerebral venous thrombosis (CVT) has been generally regarded as a rare cause of stroke with a good overall prognosis. The rarity of the disease has made it difficult to study in clinical trials, and current... more
In high-income countries, cerebral venous thrombosis (CVT) has been generally regarded as a rare cause of stroke with a good overall prognosis. The rarity of the disease has made it difficult to study in clinical trials, and current treatment guidelines for CVT are consensus based. Significant equipoise exists around multiple treatment decisions—choice of anticoagulant, duration of therapy, role of neuroimaging in therapeutic decision-making, and role for heroic therapies. Therapeutic strategies for CVT should be better refined, and there are multiple recent and ongoing trials aimed at addressing the challenge of how to best treat this disease. However, in identifying the best evidence-based treatment strategies for CVT, we will also need to identify the best primary outcomes to evaluate these therapies. Estimates from high-income European nations and Australia estimate that CVT affects ≈0.5 to 1/100 000 people per year in the general population, though the disease may remain underdiagnosed if clinical suspicion or overt findings on nonvascular neuroimaging do not prompt diagnostic venography. Observational studies report favorable functional outcomes, with 85% to 90% of patients achieving a modified Rankin Scale (mRS) score of 0 to 1 at 3 to 6 months after diagnosis. Even for those who achieve a favorable mRS outcome, CVT can remain a disabling condition. Existing long-term follow-up studies suggest that up to 60% of these generally well, young individuals have ongoing neuropsychiatric complaints, headache, fatigue, and cognitive issues, with one-quarter being unable to return to work. Further, anticoagulation with vitamin K antagonists (VKAs), the standard of care for most CVT patients, negatively impacts quality of life in younger adults with venous thromboembolism (VTE), particularly during the first few months of therapy. Typical frustrations with VKA use include disruptions to work and travel related to international normalized ratio monitoring, alterations in diet and alcohol consumption, and limitations to social activities. Those who have pursued clinical trials for therapy of CVT have chosen primary outcomes—recurrent VTE, major bleeding, and mRS at day 180—in line with therapeutic trials for more common forms of VTE and more disabling forms of stroke. However, this strategy perpetuates uncertainty for treating clinicians. Rates of recurrent VTE, major bleeding, death, and dependence in CVT are low. The rarity of CVT, compounded by the rarity of these outcomes, leaves trials underpowered. One could argue that in a trial of experimental therapy for CVT, even with an underpowered study, one would be able to exclude an approach with a highly unacceptable safety or tolerability profile. However, a focus on more common patient-centered outcomes may help to define future therapies that are acceptably safe, focused on patient needs, and supported by high-quality trial data.
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ABSTRACT:We examined the accuracy of International Classification of Disease 10th iteration (ICD-10) diagnosis codes within Canadian administrative data in identifying cerebral venous thrombosis (CVT). Of 289 confirmed cases of CVT... more
ABSTRACT:We examined the accuracy of International Classification of Disease 10th iteration (ICD-10) diagnosis codes within Canadian administrative data in identifying cerebral venous thrombosis (CVT). Of 289 confirmed cases of CVT admitted to our comprehensive stroke center between 2008 and 2018, 239/289 were new diagnoses and 204/239 were acute events with only 75/204 representing symptomatic CVTs not provoked by trauma or structural processes. Using ICD-10 codes in any position, sensitivity was 39.1% and positive predictive value was 94.2% for patients with a current or history of CVT and 84.0% and 52.5% for acute and symptomatic CVTs not provoked by trauma or structural processes.
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Background and Purpose— Patients with transient ischemic attack (TIA) and minor ischemic stroke are at risk for early recurrent cerebral ischemia. Anticoagulants are associated with reduced recurrence but also increased hemorrhagic... more
Background and Purpose— Patients with transient ischemic attack (TIA) and minor ischemic stroke are at risk for early recurrent cerebral ischemia. Anticoagulants are associated with reduced recurrence but also increased hemorrhagic transformation (HT). The safety of the novel oral anticoagulant dabigatran in acute stroke has not been evaluated. Methods— DATAS II (Dabigatran Treatment of Acute Stroke II) was a phase II prospective, randomized open label, blinded end point trial. Patients with noncardioembolic stroke/transient ischemic attack (National Institutes of Health Stroke Scale score, ≤9; infarct volume, ≤25 mL) were randomized to dabigatran or aspirin. Magnetic resonance imaging was performed before randomization and repeated at day 30. Imaging end points were ascertained centrally by readers blinded to treatment. The primary end point was symptomatic HT within 37 days of randomization. Results— A total of 305 patients, mean age 66.59±13.21 years, were randomized to dabigatran or aspirin a mean of 42.00±17.31 hours after symptom onset. The qualifying event was a transient ischemic attack in 21%, and ischemic stroke in 79% of patients. Median National Institutes of Health Stroke Scale (interquartile range) was 1 (0–2), and mean infarct volume 3.2±6.5 mL. No symptomatic HT occurred. Asymptomatic petechial HT developed in 11/142 (7.8%) of dabigatran-assigned patients and 5/142 (3.5%) of aspirin-assigned patients (relative risk, 2.301 [95% CI, 0.778–6.802]). Baseline infarct volume predicted incident HT (odds ratio, 1.07 [95% CI, 1.03–1.12]; P =0.0026). Incident covert infarcts on day 30 imaging occurred in 9/142 (6.3%) of dabigatran-assigned and 14/142 (9.8%) of aspirin-assigned patients (relative risk, 0.62 [95% CI, 0.26, 1.48]). Conclusions— Dabigatran was associated with a risk of HT similar to aspirin in acute minor noncardioembolic ischemic stroke/transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02295826.
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Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated... more
Introduction: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. Methods: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7–30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). Results: We evaluated 509 patients; median inf...
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IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces... more
IntroductionCerebral small vessel disease (cSVD) accounts for 20%–25% of strokes and is the most common cause of vascular cognitive impairment (VCI). In an animal VCI model, inducing brief periods of limb ischaemia-reperfusion reduces subsequent ischaemic brain injury with remote and local protective effects, with hindlimb remote ischaemic conditioning (RIC) improving cerebral blood flow, decreasing white-matter injury and improving cognition. Small human trials suggest RIC is safe and may prevent recurrent strokes. It remains unclear what doses of chronic daily RIC are tolerable and safe, whether effects persist after treatment cessation, and what parameters are optimal for treatment response.Methods and analysisThis prospective, open-label, randomised controlled trial (RCT) with blinded end point assessment and run-in period, will recruit 24 participants, randomised to one of two RIC intensity groups: one arm treated once daily or one arm twice daily for 30 consecutive days. RIC w...
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Background Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for... more
Background Statistical models to predict outcomes after endovascular therapy for acute ischemic stroke often incorporate baseline (pretreatment) variables only. We assessed the performance of stroke outcome prediction models for endovascular therapy in stroke in an iterative fashion using baseline, treatment‐related, and posttreatment variables. Methods Data from the ESCAPE‐NA1 (Safety and Efficacy of Nerinetide [NA‐1] in Subjects Undergoing Endovascular Thrombectomy for Stroke) trial were used to build 4 outcome prediction models using multivariable logistic regression: model 1 included baseline variables available before treatment decision making, model 2 included additional treatment‐related variables, model 3 additional posttreatment variables that become available early (within 24–48 hours), and model 4 later (beyond 48 hours) after endovascular therapy. The primary outcome was functional independence (90‐day Modified Rankin Scale score 0–2). Model performance was compared usin...