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1.
Am J Hosp Palliat Care ; : 10499091241253538, 2024 May 09.
Article En | MEDLINE | ID: mdl-38725344

Background: Palliative care (PC) aims to enhance the quality of life for patients when confronted with serious illness. As stroke inflicts high morbidity and mortality, the integration of PC within acute stroke care remains an important aspect of quality inpatient care. However, there is a tendency to offer PC to stroke patients only when death appears imminent. We aim to understand why this may be by examining stroke patients admitted to a regional stroke centre who subsequently died and their provision of PC. Methods: We conducted a retrospective single-centre cohort study of patients who died during admission to the regional stroke centre at Sunnybrook Health Sciences Centre (SHSC) in Toronto, Ontario, Canada. Baseline demographics were assessed using means, standard deviations (SD), medians, interquartile ranges (IQR), and proportions. Descriptive statistics, univariate, and multivariate analyses were performed to ascertain relationships between collected variables. Results: Univariate modeling demonstrated that older age, being female, no stroke diagnosis at admission to hospital, ischemic stroke, and comorbidities of cancer or dementia were associated with a higher incidence of palliative medicine consultation (PMC), while admission from an acute care hospital and a Glasgow Coma Scale (GCS) coma classification were associated with a lower incidence of PMC. The multivariate model identified the GCS coma-related category as the only significant factor associated with a higher incidence of death but was non-significantly related to a lower incidence of PMC. Conclusion: These results highlight continued missed opportunities for PC in stroke patients and underscore the need to better optimize PMC.

2.
Stroke Vasc Neurol ; 2024 Jan 31.
Article En | MEDLINE | ID: mdl-38296590

BACKGROUND: In ischaemic stroke, minor deficits (National Institutes of Health Stroke Scale (NIHSS) ≤5) at presentation are common but often progress, leaving patients with significant disability. We compared the efficacy and safety of intravenous thrombolysis with tenecteplase versus alteplase in patients who had a minor stroke enrolled in the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT) trial. METHODS: The AcT trial included individuals with ischaemic stroke, aged >18 years, who were eligible for standard-of-care intravenous thrombolysis. Participants were randomly assigned 1:1 to intravenous tenecteplase (0.25 mg/kg) or alteplase (0.9 mg/kg). Patients with minor deficits pre-thrombolysis were included in this post-hoc exploratory analysis. The primary efficacy outcome was the proportion of patients with a modified Rankin Score (mRS) of 0-1 at 90-120 days. Safety outcomes included mortality and symptomatic intracranial haemorrhage (sICH). RESULTS: Of the 378 patients enrolled in AcT with an NIHSS of ≤5, the median age was 71 years, 39.7% were women; 194 (51.3%) received tenecteplase and 184 (48.7%) alteplase. The primary outcome (mRS score 0-1) occurred in 100 participants (51.8%) in the tenecteplase group and 86 (47.5 %) in the alteplase group (adjusted risk ratio (RR) 1.14 (95% CI 0.92 to 1.40)). There were no significant differences in the rates of sICH (2.9% in tenecteplase vs 3.3% in alteplase group, unadjusted RR 0.79 (0.24 to 2.54)) and death within 90 days (5.5% in tenecteplase vs 11% in alteplase group, adjusted HR 0.99 (95% CI 0.96 to 1.02)). CONCLUSION: In this post-hoc analysis of patients with minor stroke enrolled in the AcT trial, safety and efficacy outcomes with tenecteplase 0.25 mg/kg were not different from alteplase 0.9 mg/kg.

3.
Stroke ; 55(3): 524-531, 2024 Mar.
Article En | MEDLINE | ID: mdl-38275116

BACKGROUND: Recent evidence from thrombolysis trials indicates the noninferiority of intravenous tenecteplase to intravenous alteplase with respect to good functional outcomes in patients with acute stroke. We examined whether the health-related quality of life (HRQOL) of patients with acute stroke differs by the type of thrombolysis treatment received. In addition, we examined the association between the modified Rankin Scale score 0 to 1 and HRQOL and patient-reported return to prebaseline stroke functioning at 90 days. METHODS: Data were from all patients included in the AcT trial (Alteplase Compared to Tenecteplase), a pragmatic, registry-linked randomized trial comparing tenecteplase with alteplase. HRQOL at 90-day post-randomization was assessed using the 5-item EuroQOL questionnaire (EQ5D), which consists of 5 items and a visual analog scale (VAS). EQ5D index values were estimated from the EQ5D items using the time tradeoff approach based on Canadian norms. Tobit regression and quantile regression models were used to evaluate the adjusted effect of tenecteplase versus alteplase treatment on the EQ5D index values and VAS score, respectively. The association between return to prebaseline stroke functioning and the modified Rankin Scale score 0 to 1 and HRQOL was quantified using correlation coefficient (r) with 95% CI. RESULTS: Of 1577 included in the intention-to-treat analysis patients, 1503 (95.3%) had complete data on the EQ5D. Of this, 769 (51.2%) were administered tenecteplase and 717 (47.7%) were female. The mean EQ5D VAS score and EQ5D index values were not significantly higher for those who received intravenous tenecteplase compared with those who received intravenous alteplase (P=0.10). Older age (P<0.01), more severe stroke assessed using the National Institutes of Health Stroke Scale (P<0.01), and longer stroke onset-to-needle time (P=0.004) were associated with lower EQ5D index and VAS scores. There was a strong association (r, 0.85 [95% CI, 0.81-0.89]) between patient-reported return to prebaseline functioning and modified Rankin Scale score 0 to 1 Similarly, there was a moderate association between return to prebaseline functioning and EQ5D index (r, 0.45 [95% CI, 0.40-0.49]) and EQ5D VAS scores (r, 0.42 [95% CI, 0.37-0.46]). CONCLUSIONS: Although there is no differential effect of thrombolysis type on patient-reported global HRQOL and EQ 5D-5L index values in patients with acute stroke, sex- and age-related differences in HRQOL were noted in this study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.


Brain Ischemia , Ischemic Stroke , Stroke , Humans , Female , Male , Tissue Plasminogen Activator , Tenecteplase/adverse effects , Fibrinolytic Agents , Ischemic Stroke/drug therapy , Quality of Life , Brain Ischemia/drug therapy , Brain Ischemia/chemically induced , Canada , Stroke/drug therapy , Stroke/chemically induced , Thrombolytic Therapy , Treatment Outcome
4.
Stroke ; 55(2): 288-295, 2024 02.
Article En | MEDLINE | ID: mdl-38174568

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.


Ischemic Stroke , Tenecteplase , Tissue Plasminogen Activator , Female , Humans , Male , Canada , Ischemic Stroke/drug therapy , Tenecteplase/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome , Workflow , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Equivalence Trials as Topic
5.
Int J Stroke ; 19(3): 322-330, 2024 Mar.
Article En | MEDLINE | ID: mdl-37731173

BACKGROUND: Carotid tandem lesions ((TL) ⩾70% stenosis or occlusion) account for 15-20% of acute stroke with large vessel occlusion. AIMS: We investigated the safety and efficacy of intravenous tenecteplase (0.25 mg/kg) versus intravenous alteplase (0.9 mg/kg) in patients with carotid TL. METHODS: This is a substudy of the alteplase compared with the tenecteplase trial. Patients with ⩾70% stenosis of the extracranial internal carotid artery (ICA) and concomitant occlusion of the intracranial ICA, M1 or M2 segments of the middle cerebral artery on baseline computed tomography angiography (CTA) were included. Primary outcome was 90-day-modified Rankin Scale (mRS) 0-1. Secondary outcomes were mRS 0-2, mortality, and symptomatic ICH (sICH). Angiographic outcomes were successful recanalization (revised Arterial Occlusive Lesion (rAOL) 2b-3) on first and successful reperfusion (eTICI 2b-3) on final angiographic acquisitions. Multivariable mixed-effects logistic regression was performed. RESULTS: Among 1577 alteplase versus tenecteplase randomized controlled trial (AcT) patients, 128 (18.8%) had carotid TL. Of these, 93 (72.7%) underwent intravenous thrombolysis plus endovascular thrombectomy (IVT + EVT), while 35 (27.3%) were treated with IVT alone. In the IVT + EVT group, tenecteplase was associated with higher odds of 90-day-mRS 0-1 (46.0% vs. 32.6%, adjusted OR (aOR) 3.21; 95% CI = 1.06-9.71) compared with alteplase. No statistically significant differences in rates of mRS 0-2 (aOR 1.53; 95% CI = 0.51-4.55), initial rAOL 2b-3 (16.3% vs. 28.6%), final eTICI 2b-3 (83.7% vs. 85.7%), and mortality (18.0% vs. 16.3%) were found. SICH only occurred in one patient. There were no differences in outcomes between thrombolytic agents in the IVT-only group. CONCLUSION: In patients with carotid TL treated with EVT, intravenous tenecteplase may be associated with similar or better clinical outcomes, similar angiographic reperfusion rates, and safety outcomes as compared with alteplase.


Arterial Occlusive Diseases , Brain Ischemia , Endovascular Procedures , Stroke , Humans , Brain Ischemia/therapy , Constriction, Pathologic , Endovascular Procedures/methods , Fibrinolytic Agents/adverse effects , Stroke/therapy , Tenecteplase/therapeutic use , Thrombectomy/methods , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
6.
Front Neurosci ; 17: 1302132, 2023.
Article En | MEDLINE | ID: mdl-38130696

Introduction: Post-stroke dysphagia is common and associated with significant morbidity and mortality, rendering bedside screening of significant clinical importance. Using voice as a biomarker coupled with deep learning has the potential to improve patient access to screening and mitigate the subjectivity associated with detecting voice change, a component of several validated screening protocols. Methods: In this single-center study, we developed a proof-of-concept model for automated dysphagia screening and evaluated the performance of this model on training and testing cohorts. Patients were admitted to a comprehensive stroke center, where primary English speakers could follow commands without significant aphasia and participated on a rolling basis. The primary outcome was classification either as a pass or fail equivalent using a dysphagia screening test as a label. Voice data was recorded from patients who spoke a standardized set of vowels, words, and sentences from the National Institute of Health Stroke Scale. Seventy patients were recruited and 68 were included in the analysis, with 40 in training and 28 in testing cohorts, respectively. Speech from patients was segmented into 1,579 audio clips, from which 6,655 Mel-spectrogram images were computed and used as inputs for deep-learning models (DenseNet and ConvNext, separately and together). Clip-level and participant-level swallowing status predictions were obtained through a voting method. Results: The models demonstrated clip-level dysphagia screening sensitivity of 71% and specificity of 77% (F1 = 0.73, AUC = 0.80 [95% CI: 0.78-0.82]). At the participant level, the sensitivity and specificity were 89 and 79%, respectively (F1 = 0.81, AUC = 0.91 [95% CI: 0.77-1.05]). Discussion: This study is the first to demonstrate the feasibility of applying deep learning to classify vocalizations to detect post-stroke dysphagia. Our findings suggest potential for enhancing dysphagia screening in clinical settings. https://github.com/UofTNeurology/masa-open-source.

7.
Stroke ; 54(11): 2766-2775, 2023 11.
Article En | MEDLINE | ID: mdl-37800372

BACKGROUND: The AcT (Alteplase Compared to Tenecteplase) randomized controlled trial showed that tenecteplase is noninferior to alteplase in treating patients with acute ischemic stroke within 4.5 hours of symptom onset. The effect of time to treatment on clinical outcomes with alteplase is well known; however, the nature of this relationship is yet to be described with tenecteplase. We assessed whether the association of time to thrombolysis treatment with clinical outcomes in patients with acute ischemic stroke differs by whether they receive intravenous tenecteplase versus alteplase. METHODS: Patients included were from AcT, a pragmatic, registry-linked, phase 3 randomized controlled trial comparing intravenous tenecteplase to alteplase in patients with acute ischemic stroke. Eligible patients were >18 years old, with disabling neurological deficits, presenting within 4.5 hours of symptom onset, and eligible for thrombolysis. Primary outcome was modified Rankin Scale score 0 to 1 at 90 days. Safety outcomes included 24-hour symptomatic intracerebral hemorrhage and 90-day mortality rates. Mixed-effects logistic regression was used to assess the following: (a) the association of stroke symptom onset to needle time; (b) door (hospital arrival) to needle time with outcomes; and (c) if these associations were modified by type of thrombolytic administered (tenecteplase versus alteplase), after adjusting for age, sex, baseline stroke severity, and site of intracranial occlusion. RESULTS: Of the 1538 patients included in this analysis, 1146 (74.5%; 591 tenecteplase and 555 alteplase) presented within 3 hours versus 392 (25.5%; 196: TNK and 196 alteplase) who presented within 3 to 4.5 hours of symptom onset. Baseline patient characteristics in the 0 to 3 hours versus 3- to 4.5-hour time window were similar, except patients in the 3- to 4.5-hour window had lower median baseline National Institutes of Health Stroke Severity Scale (10 versus 7, respectively) and lower proportion of patients with large vessel occlusion on baseline CT angiography (26.9% versus 18.7%, respectively). Type of thrombolytic agent (tenecteplase versus alteplase) did not modify the association between continuous onset to needle time (Pinteraction=0.161) or door-to-needle time (Pinteraction=0.972) and primary clinical outcome. Irrespective of the thrombolytic agent used, each 30-minute reduction in onset to needle time was associated with a 1.8% increase while every 10 minutes reduction in door-to-needle time was associated with a 0.2% increase in the probability of achieving 90-day modified Rankin Scale score 0 to 1, respectively. CONCLUSIONS: The effect of time to tenecteplase administration on clinical outcomes is like that of alteplase, with faster administration resulting in better clinical outcomes. REGISTRATION: URL: https://classic. CLINICALTRIALS: gov; Unique identifier: NCT03889249.


Brain Ischemia , Ischemic Stroke , Stroke , Adolescent , Humans , Brain Ischemia/drug therapy , Brain Ischemia/chemically induced , Fibrinolytic Agents , Ischemic Stroke/drug therapy , Tenecteplase/adverse effects , Thrombolytic Therapy/methods , Tissue Plasminogen Activator , Treatment Outcome
8.
JAMA Neurol ; 80(8): 824-832, 2023 08 01.
Article En | MEDLINE | ID: mdl-37428494

Importance: It is unknown whether intravenous thrombolysis using tenecteplase is noninferior or preferable compared with alteplase for patients with acute ischemic stroke. Objective: To examine the safety and efficacy of tenecteplase compared to alteplase among patients with large vessel occlusion (LVO) stroke. Design, Setting, and Participants: This was a prespecified analysis of the Intravenous Tenecteplase Compared With Alteplase for Acute Ischaemic Stroke in Canada (ACT) randomized clinical trial that enrolled patients from 22 primary and comprehensive stroke centers across Canada between December 10, 2019, and January 25, 2022. Patients 18 years and older with a disabling ischemic stroke within 4.5 hours of symptom onset were randomly assigned (1:1) to either intravenous tenecteplase or alteplase and were monitored for up to 120 days. Patients with baseline intracranial internal carotid artery (ICA), M1-middle cerebral artery (MCA), M2-MCA, and basilar occlusions were included in this analysis. A total of 1600 patients were enrolled, and 23 withdrew consent. Exposures: Intravenous tenecteplase (0.25 mg/kg) vs intravenous alteplase (0.9 mg/kg). Main Outcomes and Measures: The primary outcome was the proportion of modified Rankin scale (mRS) score 0-1 at 90 days. Secondary outcomes were an mRS score from 0 to 2, mortality, and symptomatic intracerebral hemorrhage. Angiographic outcomes were successful reperfusion (extended Thrombolysis in Cerebral Infarction scale score 2b-3) on first and final angiographic acquisitions. Multivariable analyses (adjusting for age, sex, National Institute of Health Stroke Scale score, onset-to-needle time, and occlusion location) were carried out. Results: Among 1577 patients, 520 (33.0%) had LVO (median [IQR] age, 74 [64-83] years; 283 [54.4%] women): 135 (26.0%) with ICA occlusion, 237 (45.6%) with M1-MCA, 117 (22.5%) with M2-MCA, and 31 (6.0%) with basilar occlusions. The primary outcome (mRS score 0-1) was achieved in 86 participants (32.7%) in the tenecteplase group vs 76 (29.6%) in the alteplase group. Rates of mRS 0-2 (129 [49.0%] vs 131 [51.0%]), symptomatic intracerebral hemorrhage (16 [6.1%] vs 11 [4.3%]), and mortality (19.9% vs 18.1%) were similar in the tenecteplase and alteplase groups, respectively. No difference was noted in successful reperfusion rates in the first (19 [9.2%] vs 21 [10.5%]) and final angiogram (174 [84.5%] vs 177 [88.9%]) among 405 patients who underwent thrombectomy. Conclusions and Relevance: The findings in this study indicate that intravenous tenecteplase conferred similar reperfusion, safety, and functional outcomes compared to alteplase among patients with LVO.


Arterial Occlusive Diseases , Brain Ischemia , Ischemic Stroke , Stroke , Humans , Female , Aged , Male , Tissue Plasminogen Activator/therapeutic use , Tenecteplase , Stroke/diagnostic imaging , Stroke/drug therapy , Fibrinolytic Agents/therapeutic use , Brain Ischemia/drug therapy , Brain Ischemia/complications , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/drug therapy , Cerebral Hemorrhage/complications , Arterial Occlusive Diseases/complications , Treatment Outcome
9.
Front Neurol ; 14: 1072020, 2023.
Article En | MEDLINE | ID: mdl-37114231

New-onset refractory status epilepticus (NORSE) is a clinical presentation where an individual develops refractory status epilepticus without active epilepsy, or related neurological conditions. A subset of these individuals has a preceding fever and would be diagnosed with febrile infection-related epilepsy syndrome (FIRES). The underlying etiology of this condition varies and includes autoimmune and viral encephalitides. These conditions require multiple specialized health care teams working collaboratively and specific resources for investigation of the underlying etiology and management to provide optimal patient care. In this paper, we provide: (1) recommendations upon early recognition of NORSE and FIRES, (2) guidance on the resources needed to optimally provide care, and (3) guidance on considerations to initiate transfer of patients to a more specialized medical center. Additional recommendations for resource-austere centers without the ability to transfer such patients are also discussed. These recommendations are only for adult patients with NORSE as pediatric patients may require additional special considerations.

10.
Am J Hosp Palliat Care ; 40(11): 1231-1260, 2023 Nov.
Article En | MEDLINE | ID: mdl-36779374

Introduction: Breaking bad news to patients and families can be challenging for healthcare providers. The present study conducted a systematic review of the literature to determine if formal communication training using the SPIKES protocol improves learner satisfaction, knowledge, performance, or system outcomes. Method: MEDLINE, Embase, CINAHL Plus (Nursing & Allied Health Sciences), and PsycINFO Databases were searched with keywords BAD NEWS and SPIKES. Studies were required to have an intervention using the SPIKES model and an outcome that addressed at least one of the four domains of the Kirkpatrick model for evaluating training effectiveness. The Cochrane Risk of Bias Tool was used to conduct a risk of bias assessment. Due to heterogeneity in the interventions and outcomes, meta-analysis was not undertaken and instead, a narrative synthesis was used with the information provided in the tables to summarise the main findings of the included studies. Results: Of 622 studies screened, 37 publications met the inclusion criteria. Interventions ranged from the use of didactic lecture, role play with standardised patients (SPs), video use, debriefing sessions, and computer simulations. Evaluation tools ranged from pre and post intervention questionnaires, OSCE performance with rating by independent raters and SPs, and reflective essay writing. Conclusions: Our systematic review demonstrated that the SPIKES protocol is associated with improved learner satisfaction, knowledge and performance. None of the studies in our review examined system outcomes. As such, further educational development and research is needed to evaluate the impact of patient outcomes, including the optimal components and length of intervention.


Communication , Health Personnel , Humans , Health Occupations , Surveys and Questionnaires
11.
J Stroke Cerebrovasc Dis ; 32(4): 106997, 2023 Apr.
Article En | MEDLINE | ID: mdl-36696725

BACKGROUND: Palliative care (PC) aims to enhance the quality of life for patients and their families when confronted with serious illness.  As stroke continues to inflict high morbidity and mortality, the integration of palliative care within acute stroke care remains an important aspect of quality inpatient care. AIM: This study aims to investigate the experiences and perceived barriers of PC integration for patients with acute severe stroke in Canadian stroke physicians. METHODS: We conducted an anonymous, descriptive, cross-sectional web-based self-administered survey of stroke physicians in Canada who engage in acute severe stroke care. The questionnaire contained three sections related to stroke physician characteristics, practice attributes, and opinions about palliative care.  Descriptive statistics, univariate, and regression analysis were performed to ascertain relations between collected variables. RESULTS: Of the 132 physician associate members, 120 were surveyed with a response rate of 69 (58%). Stroke physicians reported that PC services were consulted "sometimes" and that PC services were consulted rarely for prognostication and more often for end-of-life care which they agreed was better delivered off the stroke unit. Several barriers for early integration of palliative care services were identified including uncertainty in prognosis. Stroke physicians endorsed education of both families and physicians would be beneficial. CONCLUSIONS: There remain perceived barriers for integration of palliative care within the acute stroke population. Challenges include consultation of PC services, uncertainty around patient prognosis, engagement, and educational barriers. There are opportunities for further integration and collaboration between palliative care physicians and stroke physicians.


Physicians , Stroke , Humans , Palliative Care , Cross-Sectional Studies , Quality of Life , Canada , Attitude , Stroke/diagnosis , Stroke/therapy , Attitude of Health Personnel
12.
Lancet ; 400(10347): 161-169, 2022 07 16.
Article En | MEDLINE | ID: mdl-35779553

BACKGROUND: Intravenous thrombolysis with alteplase bolus followed by infusion is a global standard of care for patients with acute ischaemic stroke. We aimed to determine whether tenecteplase given as a single bolus might increase reperfusion compared with this standard of care. METHODS: In this multicentre, open-label, parallel-group, registry-linked, randomised, controlled trial (AcT), patients were enrolled from 22 primary and comprehensive stroke centres across Canada. Patients were eligible for inclusion if they were aged 18 years or older, with a diagnosis of ischaemic stroke causing disabling neurological deficit, presenting within 4·5 h of symptom onset, and eligible for thrombolysis per Canadian guidelines. Eligible patients were randomly assigned (1:1), using a previously validated minimal sufficient balance algorithm to balance allocation by site and a secure real-time web-based server, to either intravenous tenecteplase (0·25 mg/kg to a maximum of 25 mg) or alteplase (0·9 mg/kg to a maximum of 90mg; 0·09 mg/kg as a bolus and then a 60 min infusion of the remaining 0·81 mg/kg). The primary outcome was the proportion of patients who had a modified Rankin Scale (mRS) score of 0-1 at 90-120 days after treatment, assessed via blinded review in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment who did not withdraw consent). Non-inferiority was met if the lower 95% CI of the difference in the proportion of patients who met the primary outcome between the tenecteplase and alteplase groups was more than -5%. Safety was assessed in all patients who received any of either thrombolytic agent and who were reported as treated. The trial is registered with ClinicalTrials.gov, NCT03889249, and is closed to accrual. FINDINGS: Between Dec 10, 2019, and Jan 25, 2022, 1600 patients were enrolled and randomly assigned to tenecteplase (n=816) or alteplase (n=784), of whom 1577 were included in the ITT population (n=806 tenecteplase; n=771 alteplase). The median age was 74 years (IQR 63-83), 755 (47·9%) of 1577 patients were female and 822 (52·1%) were male. As of data cutoff (Jan 21, 2022), 296 (36·9%) of 802 patients in the tenecteplase group and 266 (34·8%) of 765 in the alteplase group had an mRS score of 0-1 at 90-120 days (unadjusted risk difference 2·1% [95% CI - 2·6 to 6·9], meeting the prespecified non-inferiority threshold). In safety analyses, 27 (3·4%) of 800 patients in the tenecteplase group and 24 (3·2%) of 763 in the alteplase group had 24 h symptomatic intracerebral haemorrhage and 122 (15·3%) of 796 and 117 (15·4%) of 763 died within 90 days of starting treatment INTERPRETATION: Intravenous tenecteplase (0·25 mg/kg) is a reasonable alternative to alteplase for all patients presenting with acute ischaemic stroke who meet standard criteria for thrombolysis. FUNDING: Canadian Institutes of Health Research, Alberta Strategy for Patient Oriented Research Support Unit.


Brain Ischemia , Ischemic Stroke , Stroke , Aged , Brain Ischemia/complications , Brain Ischemia/drug therapy , Canada , Female , Fibrinolytic Agents/therapeutic use , Humans , Ischemic Stroke/drug therapy , Male , Registries , Stroke/drug therapy , Stroke/etiology , Tenecteplase , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome
13.
J Thromb Thrombolysis ; 53(1): 17-19, 2022 Jan.
Article En | MEDLINE | ID: mdl-34232455

There is significant overlap between knowledge and its clinical application in stroke and thrombosis & vascular medicine. Formal integration of training is, however, not standard. After the hyperacute phase of management, personalized medical decisions are often needed regarding antithrombotics and anticoagulants that leverage clinical practice parameters from both disciplines with a unique emphasis on minimizing neurologic treatment complications. We completed an ad hoc survey of adult thrombosis fellowships at several North American centers. We discovered that direct integration of training programs is not prevalent, suggesting a role for more deliberate integration of training programs. We provide a framework and resources for consideration that directly improve, by design, integrated clinical experiences during training, harnessing the strengths in both stroke and thrombosis programs.


Stroke , Thrombosis , Fellowships and Scholarships , Humans , Stroke/therapy , Thrombosis/therapy
15.
J Cereb Blood Flow Metab ; 41(10): 2756-2768, 2021 10.
Article En | MEDLINE | ID: mdl-33969731

Ischemia is one of the most common causes of acquired brain injury. Central to its noxious sequelae are spreading depolarizations (SDs), waves of persistent depolarizations which start at the location of the flow obstruction and expand outwards leading to excitotoxic damage. The majority of acute stage of stroke studies to date have focused on the phenomenology of SDs and their association with brain damage. In the current work, we investigated the role of peri-injection zone pyramidal neurons in triggering SDs by optogenetic stimulation in an endothelin-1 rat model of focal ischemia. Our concurrent two photon fluorescence microscopy data and local field potential recordings indicated that a ≥ 60% drop in cortical arteriolar red blood cell velocity was associated with SDs at the ET-1 injection site. SDs were also observed in the peri-injection zone, which subsequently exhibited elevated neuronal activity in the low-frequency bands. Critically, SDs were triggered by low- but not high-frequency optogenetic stimulation of peri-injection zone pyramidal neurons. Our findings depict a complex etiology of SDs post focal ischemia and reveal that effects of neuronal modulation exhibit spectral and spatial selectivity.


Cortical Spreading Depression/physiology , Endothelin-1/metabolism , Stroke/physiopathology , Animals , Disease Models, Animal , Rats
16.
Neurol Clin Pract ; 11(2): e165-e169, 2021 Apr.
Article En | MEDLINE | ID: mdl-33842086

We describe the University of Toronto Adult Neurology Residency Program's early experiences with and response to the coronavirus disease 2019 pandemic, including modifications to the provision of neurologic care while upholding neurology education and safety. All academic and many patient-related activities were virtualized. This maintained physical distancing while creating a city-wide videoconference-based teaching curriculum, expanding the learning opportunities to trainees at all academic sites. Furthermore, we propose a novel split-team model to promote resident safety through physical distancing of teams and to establish a capacity to rapidly adapt to redeployment, service needs, and trainee illness. Finally, we developed a unique protected code stroke framework to safeguard staff and trainees during hyperacute stroke assessments in this pandemic. Our shared experiences highlight considerations for contingency planning, maintenance of education, sustainability of team members, and promotion of safe neurologic care. These interventions serve to promote trainee safety, wellness, and resiliency.

18.
Am J Hosp Palliat Care ; 38(11): 1356-1360, 2021 Nov.
Article En | MEDLINE | ID: mdl-33401952

OBJECTIVES: Current guidelines suggest that patients with severe dementia on cholinesterase inhibitors (CHEIs) should discontinue their CHEIs by taper. This study aims to define the prevalence of patients admitted to a palliative care unit (PCU) with dementia on a CHEI and to determine whether these patients were tapered off their CHEIs according to current deprescribing guidelines. DESIGN: This is a descriptive retrospective chart review that examined patients admitted to a PCU with dementia on a CHEI from January 2015 to June 2019. METHODS: Individuals admitted to the PCU with a primary or comorbid diagnosis of dementia were identified. Their corresponding CHEI dose, frequency and discontinuation pattern were identified. Data were analyzed using descriptive statistics. RESULTS: A total of 36 patients were admitted to the PCU with dementia on a CHEI (prevalence of 2.3%). The median length of stay was 21 days. For 31 of these patients, their CHEI was discontinued, only 9 of which had a taper. Of the 24 patients who discontinued their CHEI suddenly, 10 patients had an order to discontinue their CHEI in the last 2 days before their date of death. CONCLUSION: This study suggests that although patients admitted to a PCU with dementia have their CHEI discontinued, the discontinuation was done without a taper. In many cases the CHEIs were continued through the active stage of dying. Future work should explore reasons why PCU physicians are mostly late to taper CHEIs for patients admitted with dementia.


Alzheimer Disease , Dementia , Hospice and Palliative Care Nursing , Cholinesterase Inhibitors/therapeutic use , Dementia/drug therapy , Dementia/epidemiology , Humans , Palliative Care , Retrospective Studies
20.
Neurocrit Care ; 33(2): 338-346, 2020 10.
Article En | MEDLINE | ID: mdl-32794144

BACKGROUND AND PURPOSE: Management of stroke patients in the acute setting is a high-stakes task with several challenges including the need for rapid assessment and treatment, maintenance of high-performing team dynamics, management of cognitive load affecting providers, and factors impacting team communication. Crisis resource management (CRM) provides a framework to tackle these challenges and is well established in other resuscitative disciplines. The current Coronavirus Disease 2019 (COVID-19) pandemic has exposed a potential quality gap in emergency preparedness and the ability to adapt to emergency scenarios in real time. METHODS: Available resources in the literature in other disciplines and expert consensus were used to identify key elements of CRM as they apply to acute stroke management. RESULTS: We outline essential ingredients of CRM as a means to mitigate nontechnical challenges providers face during acute stroke care. These strategies include situational awareness, triage and prioritization, mitigation of cognitive load, team member role clarity, communication, and debriefing. Incorporation of CRM along with simulation is an established tool in other resuscitative disciplines and can be incorporated into acute stroke care. CONCLUSIONS: As stroke care processes evolve during these trying times, the importance of consistent, safe, and efficacious care facilitated by CRM principles offers a unique avenue to alleviate human factors and support high-performing teams.


Betacoronavirus , Coronavirus Infections/epidemiology , Health Resources/organization & administration , Pneumonia, Viral/epidemiology , Stroke/therapy , COVID-19 , Humans , Pandemics , SARS-CoV-2
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