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  • 1
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    Online Resource
    Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort
    Wiley ; 2023
    In:  Alzheimer's & Dementia Vol. 19, No. 1 ( 2023-01), p. 226-243
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 19, No. 1 ( 2023-01), p. 226-243
    Abstract: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. Methods This multi‐site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. Results We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. Discussion Data will be shared with the global scientific community. Within‐disease and disease‐agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v19.1
    DOI: 10.1002/alz.12632
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2201940-6
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  • 2
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    Contribution of rare variant associations to neurodegenerative disease presentation
    Springer Science and Business Media LLC ; 2021
    In:  npj Genomic Medicine Vol. 6, No. 1 ( 2021-09-28)
    Details
    In: npj Genomic Medicine, Springer Science and Business Media LLC, Vol. 6, No. 1 ( 2021-09-28)
    Abstract: Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted to fill the gaps by performing linkage analyses and association studies in individual disease cohorts, but have failed to consider the clinical and pathological overlap observed across neurodegenerative diseases and the potential for genetic overlap between the phenotypes. Here, we leveraged rare variant association analyses (RVAAs) to elucidate the genetic overlap among multiple neurodegenerative diagnoses, including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), mild cognitive impairment, and Parkinson’s disease (PD), as well as cerebrovascular disease, using the data generated with a custom-designed neurodegenerative disease gene panel in the Ontario Neurodegenerative Disease Research Initiative (ONDRI). As expected, only ~3% of ONDRI participants harboured a monogenic variant likely driving their disease presentation. Yet, when genes were binned based on previous disease associations, we observed an enrichment of putative loss of function variants in PD genes across all ONDRI cohorts. Further, individual gene-based RVAA identified significant enrichment of rare, nonsynonymous variants in PARK2 in the FTD cohort, and in NOTCH3 in the PD cohort. The results indicate that there may be greater heterogeneity in the genetic factors contributing to neurodegeneration than previously appreciated. Although the mechanisms by which these genes contribute to disease presentation must be further explored, we hypothesize they may be a result of rare variants of moderate phenotypic effect contributing to overlapping pathology and clinical features observed across neurodegenerative diagnoses.
    Type of Medium: Online Resource
    ISSN: 2056-7944
    URL: Article
    DOI: 10.1038/s41525-021-00243-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2813848-X
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  • 3
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    Online Resource
    Subtherapeutic Warfarin Is Not Associated With Increased Hemorrhage Rates in Ischemic Strokes Treated With Tissue Plasminogen Activator
    Ovid Technologies (Wolters Kluwer Health) ; 2011
    In:  Stroke Vol. 42, No. 4 ( 2011-04), p. 1041-1045
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 4 ( 2011-04), p. 1041-1045
    Abstract: Concern exists that preadmission warfarin use may be associated with an increased risk of intracerebral hemorrhage in patients with ischemic stroke receiving intravenous tissue plasminogen activator, even in those with an international normalized ratio 〈 1.7. However, evidence to date has been derived from a small single-center cohort of patients. Methods— We used data from Phase 3 of the Registry of the Canadian Stroke Network. We compared the rates of post-tissue plasminogen activator hemorrhage, including any intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and gastrointestinal hemorrhage in patients with and without preadmission warfarin use. For those receiving warfarin, we restricted the analysis to patients with an international normalized ratio 〈 1.7 on presentation. Secondary outcomes included functional status and mortality. Multivariate analyses were performed to adjust for other prognostic factors. Results— Our cohort included 1739 patients with acute ischemic stroke treated with intravenous tissue plasminogen activator of whom 125 (7.2%) were receiving warfarin before admission and had an international normalized ratio 〈 1.7. Preadmission warfarin use was not associated with any secondary intracerebral hemorrhage (OR, 1.2; 95% CI, 0.7 to 2.2), symptomatic intracerebral hemorrhage (OR, 1.1; 95% CI, 0.5 to 2.3), or gastrointestinal hemorrhage (OR, 1.1; 95% CI, 0.2 to 5.6). Multivariate analysis showed that preadmission warfarin use was independently associated with a reduced risk of poor functional outcome (OR, 0.6; 95 CI, 0.3 to 0.9), but not with in-hospital mortality (OR, 0.6; 95% CI, 0.3 to 1.0). Conclusions— The results from the present study suggest that tissue plasminogen activator treatment appears to be safe in patients with acute ischemic stroke taking warfarin with an international normalized ratio 〈 1.7 and may reduce the risk of poor functional outcome.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.110.599183
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2011
    detail.hit.zdb_id: 1467823-8
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  • 4
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    Stroke care and case fatality in people with and without schizophrenia: a retrospective cohort study
    BMJ ; 2021
    In:  BMJ Open Vol. 11, No. 6 ( 2021-06), p. e044766-
    Details
    In: BMJ Open, BMJ, Vol. 11, No. 6 ( 2021-06), p. e044766-
    Abstract: Schizophrenia is associated with an increased risk of death following stroke; however, the magnitude and underlying reasons for this are not well understood. Objective To determine the association between schizophrenia and stroke case fatality, adjusting for baseline characteristics, stroke severity and processes of care. Design Retrospective cohort study used linked clinical and administrative databases. Setting All acute care institutions (N=152) in the province of Ontario, Canada. Participants All patients (N=52 473) hospitalised with stroke between 1 April 2002 and 31 March 2013 and included in the Ontario Stroke Registry. Those with schizophrenia (n=612) were identified using validated algorithms. Main outcomes and measures We compared acute stroke care in those with and without schizophrenia and used Cox proportional hazards models to examine the association between schizophrenia and mortality, adjusting for demographics, comorbidity, stroke severity and processes of care. Results Compared with those without schizophrenia, people with schizophrenia were less likely to undergo thrombolysis (10.1% vs 13.4%), carotid imaging (66.3% vs 74.0%), rehabilitation (36.6% vs 46.6% among those with disability at discharge) or be treated with antihypertensive, lipid-lowering or anticoagulant therapies. After adjustment for age and other factors, schizophrenia was associated with death from any cause at 1 year (adjusted HR (aHR) 1.33, 95% CI 1.14 to 1.54). This was mainly attributable to early deaths from stroke (aHR 1.47, 95% CI 1.20 to 1.80, with survival curves separating in the first 30 days), and the survival disadvantage was particularly marked in those aged over 70 years (1-year mortality 46.9% vs 35.0%). Conclusions Schizophrenia is associated with increased stroke case fatality, which is not fully explained by stroke severity, measurable comorbid conditions or processes of care. Future work should focus on understanding this mortality gap and on improving acute stroke and secondary preventive care in people with schizophrenia.
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    URL: Article
    DOI: 10.1136/bmjopen-2020-044766
    Language: English
    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 2599832-8
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  • 5
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    Canadian Stroke Best Practice Recommendations : Hyperacute Stroke Care Guidelines, Update 2015
    SAGE Publications ; 2015
    In:  International Journal of Stroke Vol. 10, No. 6 ( 2015-08), p. 924-940
    Details
    In: International Journal of Stroke, SAGE Publications, Vol. 10, No. 6 ( 2015-08), p. 924-940
    Abstract: The 2015 update of the Canadian Stroke Best Practice Recommendations Hyperacute Stroke Care guideline highlights key elements involved in the initial assessment, stabilization, and treatment of patients with transient ischemic attack (TIA), ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, and acute venous sinus thrombosis. The most notable change in this 5th edition is the addition of new recommendations for the use of endovascular therapy for patients with acute ischemic stroke and proximal intracranial arterial occlusion. This includes an overview of the infrastructure and resources required for stroke centers that will provide endovascular therapy as well as regional structures needed to ensure that all patients with acute ischemic stroke that are eligible for endovascular therapy will be able to access this newly approved therapy; recommendations for hyperacute brain and enhanced vascular imaging using computed tomography angiography and computed tomography perfusion; patient selection criteria based on the five trials of endovascular therapy published in early 2015, and performance metric targets for important time-points involved in endovascular therapy, including computed tomography-to-groin puncture and computed tomography-to-reperfusion times. Other updates in this guideline include recommendations for improved time efficiencies for all aspects of hyperacute stroke care with a movement toward a new median target door-to-needle time of 30 min, with the 90th percentile being 60 min. A stronger emphasis is placed on increasing public awareness of stroke with the recent launch of the Heart and Stroke Foundation of Canada FAST signs of stroke campaign; reinforcing the public need to seek immediate medical attention by calling 911; further engagement of paramedics in the prehospital phase with prehospital notification to the receiving emergency department, as well as the stroke team, including neuroradiology; updates to the triage and same-day assessment of patients with transient ischemic attack; updates to blood pressure recommendations for the hyperacute phase of care for ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The goal of these recommendations and supporting materials is to improve efficiencies and minimize the absolute time lapse between stroke symptom onset and reperfusion therapy, which in turn leads to better outcomes and potentially shorter recovery times.
    Type of Medium: Online Resource
    ISSN: 1747-4930 , 1747-4949
    URL: Article
    DOI: 10.1111/ijs.12551
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2015
    detail.hit.zdb_id: 2211666-7
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  • 6
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    Improving reperfusion time within the ESCAPE Endovascular Clinical Trial
    SAGE Publications ; 2017
    In:  European Stroke Journal Vol. 2, No. 1 ( 2017-03), p. 64-69
    Details
    In: European Stroke Journal, SAGE Publications, Vol. 2, No. 1 ( 2017-03), p. 64-69
    Abstract: Endovascular treatment of acute ischemic stroke is more effective when performed quickly. In this report, we describe quality interventions to ensure fast endovascular treatment times in the ESCAPE (Endovascular Treatment for Small Core and Anterior circulation Proximal Occlusion with Emphasis on Minimizing CT to Recanalization Times) trial. Methods An “audit and feedback” intervention using webinar and letter was used to improve treatment time over the course of the trial. The time metrics were computed tomography-to-groin-puncture (target  〈  60 min) and computed tomography-to-first-reperfusion (target  〈  90 min). Each site was provided with their data for computed tomography-to-groin-puncture and computed tomography-to-first-reperfusion for all their patients that were randomized to the treatment arm, and their median time was compared to the overall median times of all sites in the trial. We assessed for changes in treatment time over the course of the trial. Results There were 165 patients enrolled into the endovascular arm from 22 sites. The computed tomography-to-groin-puncture time dropped from 57 to 47 min (p = 0.14) while computed tomography-to-reperfusion time dropped from 89 to 81 min (p = 0.48). Over the course of the trial, the absolute treatment benefit increased by 7.8% (p  〈  0.001). Conclusions An “audit and feedback” intervention throughout the conduct of the ESCAPE trial was a feasible way to ensure fast treatment times. Quality improvement processes should continue as standard practice beyond the trial to encourage good patient selection and the best clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 2396-9873 , 2396-9881
    URL: Article
    DOI: 10.1177/2396987316681176
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2017
    detail.hit.zdb_id: 2851287-X
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  • 7
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    Online Resource
    Predicting Cognitive Impairment in Cerebrovascular Disease Using Spoken Discourse Production
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Topics in Language Disorders Vol. 41, No. 1 ( 2021-01), p. 73-98
    Details
    In: Topics in Language Disorders, Ovid Technologies (Wolters Kluwer Health), Vol. 41, No. 1 ( 2021-01), p. 73-98
    Abstract: Dementia due to cerebrovascular disease (CVD) is common. Detecting early cognitive decline in CVD is critical because addressing risk factors may slow or prevent dementia. This study used a multidomain discourse analysis approach to determine the spoken language signature of CVD-related cognitive impairment. Method: Spoken language and neuropsychological assessment data were collected prospectively from 157 participants with CVD as part of the Ontario Neurodegenerative Disease Research Initiative, a longitudinal, observational study of neurodegenerative disease. Participants were categorized as impaired ( n = 92) or cognitively normal for age ( n = 65) based on neuropsychology criteria. Spoken language samples were transcribed orthographically and annotated for 13 discourse features, across five domains. Discriminant function analyses were used to determine a minimum set of discourse variables, and their estimated weights, for maximizing diagnostic group separation. Results: The optimal discriminant function that included 10 of 13 discourse measures correctly classified 78.3% of original cases (69.4% cross-validated cases) with a sensitivity of 77.2% and specificity of 80.0%. Conclusion: Spoken discourse appears to be a sensitive measure for detecting cognitive impairment in CVD with measures of productivity, information content, and information efficiency heavily weighted in the final algorithm.
    Type of Medium: Online Resource
    ISSN: 0271-8294
    URL: Article
    DOI: 10.1097/TLD.0000000000000242
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2095127-9
    SSG: 7,11
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  • 8
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    Abstract TP160: Predicting Bone Fracture After Stroke—The Fracture Risk After Ischemic Stroke (FRAC-Stroke) Score
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Stroke Vol. 48, No. suppl_1 ( 2017-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 48, No. suppl_1 ( 2017-02)
    Abstract: Background: Risk for low trauma fracture is increased by 〉 30% after ischemic stroke. Additionally, in the IRIS trial pioglitazone therapy prevented ischemic stroke but increased fracture risk. We derived a risk score to predict risk of fracture one year after ischemic stroke. Methods: The Fracture Risk after Ischemic Stroke (FRAC-Stroke) Score was derived in 20,435 ischemic stroke patients from the Ontario Stroke Registry discharged from 2003-2012, using Fine-Gray competing risk regression. Candidate variables were medical conditions included in the validated World Health Organization FRAX risk score complemented by variables related to stroke severity. Registry patients were linked to population-based Ontario health administrative data to identify low trauma fractures (defined as any fracture of the femur, forearm, humerus, pelvis or vertebrae, excluding fractures resulting from trauma, motor vehicle accidents, falls from a height or in people with active cancer). The score was externally validated in 13,698 other ischemic stroke patients in the population-based Ontario stroke audit (2002-2012). Results: Mean age was 72; 42% were women. Low trauma fracture occurred within 1 year of discharge in 741/20435 (3.6%); cumulative incidence increased linearly throughout follow-up. Age, discharge modified Rankin score (mRS), and history of arthritis, osteoporosis, falls and previous fracture contributed significantly to the model. Model discrimination was good (c statistic 0.72). Including discharge mRS significantly improved discrimination (relative integrated discrimination index 8.7%). Fracture risk was highest in patients with mRS 3 and 4 but lowest in bedbound patients (mRS 5). From the lowest to the highest FRAC-Stroke quintile the cumulative incidence of 1-year low trauma fracture increased from 1% to 9%. Predicted and observed rates of fracture were similar in the external validation cohort. Conclusion: The FRAC-Stroke score allows the clinician to identify ischemic stroke patients at higher risk of low trauma fracture within one year. This information might be used to target patients for early bone densitometry screening to diagnose and manage osteoporosis, and to estimate baseline risk prior to starting pioglitazone therapy.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.48.suppl_1.tp160
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467823-8
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  • 9
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    Online Resource
    Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review
    Cambridge University Press (CUP) ; 2016
    In:  Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques Vol. 43, No. 4 ( 2016-07), p. 455-460
    Details
    In: Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques, Cambridge University Press (CUP), Vol. 43, No. 4 ( 2016-07), p. 455-460
    Abstract: Étude systématique de l’utilisation de la thrombectomie mécanique dans les cas d’AVC ischémiques aigus. Bien que la thrombolyse intraveineuse augmente la probabilité d’une récupération fonctionnelle satisfaisante chez des patients dûment sélectionnés ayant souffert d’un AVC ischémique aigu, une proportion élevée de patients ayant bénéficié de cette technique médicale peinent à récupérer adéquatement. Plusieurs essais cliniques récents en matière de thrombectomie mécanique semblent indiquer que ce traitement pourrait être supérieur à la thrombolyse. Nous avons ainsi procédé de façon systématique à une recension méta-analytique devant évaluer l’efficacité clinique et l’innocuité d’une nouvelle génération de dispositifs mécaniques de thrombectomie en comparaison avec la thrombolyse intraveineuse administrée, sous réserve de certains critères d’admissibilité, à des patients ayant souffert d’un AVC ischémique aigu causé par une occlusion intracrânienne proximale. À cet égard, nous avons systématiquement interrogé sept bases de données afin de retracer des essais randomisés contrôlés dont les résultats ont été publiés entre janvier 2005 et mars 2015. Ces essais comparaient l’efficacité des extracteurs d’endoprothèses ( stent retrievers ) ou des dispositifs de thrombo-aspiration aux meilleurs traitements médicaux, accompagnés ou non de la thrombolyse intraveineuse, chez des adultes ayant souffert d’un AVC ischémique aigu. Nous avons aussi évalué la qualité d’ensemble ainsi que les risques de biais de ces essais randomisés. Le cas échéant, nous avons combiné les données au moyen d’une méta-analyse à effets aléatoires ou fixes. Au total, nous avons repéré 1579 études; de ce nombre, nous en avons évalué 122 dans leur intégralité et inclus cinq essais randomisés contrôlés (n = 1287). Comparativement à des patients ayant reçu un traitement médical « conservateur », ceux ayant bénéficié d’une thrombectomie mécanique étaient plus susceptibles de récupérer leur autonomie fonctionnelle, laquelle a été mesurée par l’échelle de Rankin modifiée entre 0 et 2 (rapport des chances ou odds ratio : 2,39; intervalle de confiance à 95% ; 1,88-3,04; I2 = 0%). Les résultats d’analyse de ce sous-groupe se sont également révélés robustes. Tant la mortalité que des manifestations d’hémorragie intracérébrale symptomatiques ne se sont pas apparues foncièrement différentes d’un groupe à l’autre. On peut donc conclure que la thrombectomie mécanique améliore de façon notable l’autonomie fonctionnelle de patients dûment sélectionnés ayant souffert d’un AVC ischémique aigu.
    Type of Medium: Online Resource
    ISSN: 0317-1671 , 2057-0155
    URL: Article
    DOI: 10.1017/cjn.2016.30
    RVK:
    XA 10000
    Language: English
    Publisher: Cambridge University Press (CUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2577275-2
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  • 10
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    Online Resource
    Hemodynamic Features of Symptomatic Vertebrobasilar Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Stroke Vol. 46, No. 7 ( 2015-07), p. 1850-1856
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 46, No. 7 ( 2015-07), p. 1850-1856
    Abstract: Atherosclerotic vertebrobasilar disease is an important cause of posterior circulation stroke. To examine the role of hemodynamic compromise, a prospective multicenter study, Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS), was conducted. Here, we report clinical features and vessel flow measurements from the study cohort. Methods— Patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries (BA) were enrolled. Large-vessel flow in the vertebrobasilar territory was assessed using quantitative MRA. Results— The cohort (n=72; 44% women) had a mean age of 65.6 years; 72% presented with ischemic stroke. Hypertension (93%) and hyperlipidemia (81%) were the most prevalent vascular risk factors. BA flows correlated negatively with percentage stenosis in the affected vessel and positively to the minimal diameter at the stenosis site ( P 〈 0.01). A relative threshold effect was evident, with flows dropping most significantly with ≥80% stenosis/occlusion ( P 〈 0.05). Tandem disease involving the BA and either/both vertebral arteries had the greatest negative impact on immediate downstream flow in the BA (43 mL/min versus 71 mL/min; P =0.01). Distal flow status assessment, based on an algorithm incorporating collateral flow by examining distal vessels (BA and posterior cerebral arteries), correlated neither with multifocality of disease nor with severity of the maximal stenosis. Conclusions— Flow in stenotic posterior circulation vessels correlates with residual diameter and drops significantly with tandem disease. However, distal flow status, incorporating collateral capacity, is not well predicted by the severity or location of the disease.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.115.009215
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 1467823-8
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