Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial.

BACKGROUND: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. METHODS: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0-5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. FINDINGS: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88-1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4-10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9-19·7, p=0·059). INTERPRETATION: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis. FUNDING: Heart and Stroke Foundation of Canada, Canadian Institutes of Health Research, and the British Heart Foundation.

Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.

Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

INTRODUCTION: 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.

Screening and Treatment for Osteoporosis After Stroke.

Background and Purpose- Stroke is a risk factor for subsequent osteoporosis and fractures. We sought to understand current rates and predictors of screening and treatment for bone loss after stroke. Methods- Using the Ontario Stroke Registry from July 1, 2003 to March 31, 2013, we identified patients ≥65 years who were seen in the emergency department or hospitalized with stroke at 11 regional stroke centers in Ontario, Canada and discharged alive. We calculated the cumulative incidence of (1) screening with bone mineral density testing and (2) treatment with medications for fracture prevention, within 1 year after the index stroke, accounting for the competing risk of death. We then used cause-specific hazard models to estimate the effect of various covariates on the cause-specific hazard of bone mineral density testing and osteoporosis pharmacotherapy. Results- In the sample of 16 581 patients, 5.1% overall and 2.9% of those without prior testing underwent screening bone mineral density testing, and 15.5% overall and 3.2% of those not previously on treatment were prescribed medications for fracture prevention within 1 year after stroke. Results were similar in all subgroups of patients. Female sex, prestroke osteoporosis, and poststroke falls and fractures were associated with increased rates of osteoporosis pharmacotherapy. Conclusions- Patients with recent stroke are infrequently screened and treated for osteoporosis, which may increase the risk of fractures. Future work should focus on identifying and treating patients who are at increased risk of fractures after stroke.

Early Trajectory of Stroke Severity Predicts Long-Term Functional Outcomes in Ischemic Stroke Subjects: Results From the ESCAPE Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

BACKGROUND AND PURPOSE: The trajectory of neurological improvement after stroke treatment is clinically likely to be an important prognostic signal. We compared the accuracy of early longitudinal National Institutes of Health Stroke Scale (NIHSS) measurement versus other early markers of stroke severity post treatment in predicting subjects' 90-day stroke outcome. METHODS: Data are from the Endovascular treatment for Small Core and Anterior circulation Proximal occlusion with ESCAPE trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). Stroke severity was assessed at baseline, 1, 2, 5, 30, and 90 days. Subjects' functional outcome was assessed using the modified Rankin Scale at baseline, 30 days, and 90 days. Group-based trajectory model was used to identify distinct subgroups of longitudinal trajectories of NIHSS measured over the first 2, 5, and 30 days. The accuracy of baseline NIHSS, infarct volume, 24-hour change in NIHSS, infarct volume, and disease severity trajectory subgroups in predicting 90-day stroke outcome were assessed using logistic regression analysis. RESULTS: Group-based trajectory model of the 2-day longitudinal NIHSS data revealed 3 distinct subgroups of NIHSS trajectories-large improvement (41.6%), minimal improvement (31.1%), and no improvement (27.3%) subgroups. Individuals in the large improvement group were more likely were more likely to exhibit good outcomes after 90 days than those in the minimal improvement or no improvement subgroup. Among candidate predictors, the 2-day trajectory subgroup variable was the most accurate in predicting 90-day modified Rankin Scale at 84.5%. CONCLUSIONS: Early trajectory of neurological improvement defined by 2-day longitudinal NIHSS data predicts functional outcomes with greater accuracy than other common variables. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Atrial fibrillation in patients with cryptogenic stroke.

BACKGROUND: Atrial fibrillation is a leading preventable cause of recurrent stroke for which early detection and treatment are critical. However, paroxysmal atrial fibrillation is often asymptomatic and likely to go undetected and untreated in the routine care of patients with ischemic stroke or transient ischemic attack (TIA). METHODS: We randomly assigned 572 patients 55 years of age or older, without known atrial fibrillation, who had had a cryptogenic ischemic stroke or TIA within the previous 6 months (cause undetermined after standard tests, including 24-hour electrocardiography [ECG]), to undergo additional noninvasive ambulatory ECG monitoring with either a 30-day event-triggered recorder (intervention group) or a conventional 24-hour monitor (control group). The primary outcome was newly detected atrial fibrillation lasting 30 seconds or longer within 90 days after randomization. Secondary outcomes included episodes of atrial fibrillation lasting 2.5 minutes or longer and anticoagulation status at 90 days. RESULTS: Atrial fibrillation lasting 30 seconds or longer was detected in 45 of 280 patients (16.1%) in the intervention group, as compared with 9 of 277 (3.2%) in the control group (absolute difference, 12.9 percentage points; 95% confidence interval [CI], 8.0 to 17.6; P<0.001; number needed to screen, 8). Atrial fibrillation lasting 2.5 minutes or longer was present in 28 of 284 patients (9.9%) in the intervention group, as compared with 7 of 277 (2.5%) in the control group (absolute difference, 7.4 percentage points; 95% CI, 3.4 to 11.3; P<0.001). By 90 days, oral anticoagulant therapy had been prescribed for more patients in the intervention group than in the control group (52 of 280 patients [18.6%] vs. 31 of 279 [11.1%]; absolute difference, 7.5 percentage points; 95% CI, 1.6 to 13.3; P=0.01). CONCLUSIONS: Among patients with a recent cryptogenic stroke or TIA who were 55 years of age or older, paroxysmal atrial fibrillation was common. Noninvasive ambulatory ECG monitoring for a target of 30 days significantly improved the detection of atrial fibrillation by a factor of more than five and nearly doubled the rate of anticoagulant treatment, as compared with the standard practice of short-duration ECG monitoring. (Funded by the Canadian Stroke Network and others; EMBRACE ClinicalTrials.gov number, NCT00846924.).

Infarct in a New Territory After Treatment Administration in the ESCAPE Randomized Controlled Trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times).

BACKGROUND AND PURPOSE: Infarct in a new previously unaffected territory (INT) is a potential complication of endovascular treatment. We applied a recently proposed methodology to identify and classify INTs in the ESCAPE randomized controlled trial (Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times). METHODS: The core laboratory identified INTs on 24-hour follow-up imaging, blinded to treatment allocation, after assessing all baseline imaging. INTs were classified into 3 types (I-III) and 2 subtypes (A/B) based on size and if catheter manipulation was likely performed across the vessel territory ostium. Logistic regression was used to understand the effect of multiple a priori identified variables on INT occurrence. Ordinal logistic regression was used to analyze the effect of INTs on modified Rankin Scale shift at 90 days. RESULTS: From 308 patients included, 14 INTs (4.5% overall; 2.8% on follow-up noncontrast computed tomography, 11.7% on follow-up magnetic resonance imaging) were identified (5.0% in endovascular treatment arm versus 4.0% in control arm [P=0.7]). The use of intravenous alteplase was associated with a 68% reduction in the odds of INT occurrence (3.0% with versus 9.1% without; odds ratio, 0.32; 95% confidence interval, 0.11-0.96; adjusted for age, sex, and treatment type). No other variables were associated with INTs. INT occurrence was associated with reduced probability of good clinical outcome (common odds ratio, 0.25; 95% confidence interval, 0.09-0.74; adjusted for age, type of treatment, and follow-up scan). CONCLUSIONS: INTs are uncommon, detected more frequently on follow-up magnetic resonance imaging, and affect clinical outcome. In experienced centers, endovascular treatment is likely not causal, whereas intravenous alteplase may be therapeutic. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01778335.

Predictors of Hospitalization in Patients With Transient Ischemic Attack or Minor Ischemic Stroke.

BACKGROUND: Transient ischemic attack (TIA) and minor stroke are associated with a substantial risk of subsequent stroke; however, there is uncertainty about whether such patients require admission to hospital for their initial management. We used data from a clinical stroke registry to determine the frequency and predictors of hospitalization for TIA or minor stroke across the province of Ontario, Canada. METHODS: The Ontario Stroke Registry collects information on a population-based sample of all patients seen in the emergency department with acute stroke or TIA in Ontario. We identified patients with minor ischemic stroke or TIA included in the registry between April 1, 2008, and March 31, 2011, and used multivariable analyses to evaluate predictors of hospitalization. RESULTS: Our study sample included 8540 patients with minor ischemic stroke or TIA, 47.2% of whom were admitted to hospital, with a range of 37.6% to 70.3% across Ontario's 14 local health integration network regions. Key predictors of admission were preadmission disability, vascular risk factors, presentation with weakness, speech disturbance or prolonged/persistent symptoms, arrival by ambulance, and presentation on a weekend or during periods of emergency department overcrowding. CONCLUSIONS: More than one-half of patients with minor stroke or TIA were not admitted to the hospital, and there were wide regional variations in admission patterns. Additional work is needed to provide guidance to health care workers around when to admit such patients and to determine whether discharged patients are receiving appropriate follow-up care.

Mechanical Thrombectomy in Acute Ischemic Stroke: A Systematic Review.

Although intravenous thrombolysis increases the probability of a good functional outcome in carefully selected patients with acute ischemic stroke, a substantial proportion of patients who receive thrombolysis do not have a good outcome. Several recent trials of mechanical thrombectomy appear to indicate that this treatment may be superior to thrombolysis. We therefore conducted a systematic review and meta-analysis to evaluate the clinical effectiveness and safety of new-generation mechanical thrombectomy devices with intravenous thrombolysis (if eligible) compared with intravenous thrombolysis (if eligible) in patients with acute ischemic stroke caused by a proximal intracranial occlusion. We systematically searched seven databases for randomized controlled trials published between January 2005 and March 2015 comparing stent retrievers or thromboaspiration devices with best medical therapy (with or without intravenous thrombolysis) in adults with acute ischemic stroke. We assessed risk of bias and overall quality of the included trials. We combined the data using a fixed or random effects meta-analysis, where appropriate. We identified 1579 studies; of these, we evaluated 122 full-text papers and included five randomized control trials (n=1287). Compared with patients treated medically, patients who received mechanical thrombectomy were more likely to be functionally independent as measured by a modified Rankin score of 0-2 (odds ratio, 2.39; 95% confidence interval, 1.88-3.04; I2=0%). This finding was robust to subgroup analysis. Mortality and symptomatic intracerebral hemorrhage were not significantly different between the two groups. Mechanical thrombectomy significantly improves functional independence in appropriately selected patients with acute ischemic stroke.

The Operational and Economic Impact of a Neurovascular Unit in an Acute Care Academic Hospital.

BACKGROUND: There is strong evidence that clinical outcomes are improved for stroke patients admitted to specialized Stroke Units. The Toronto Western Hospital (TWH) created a Neurovascular Unit (NVU) using resources from General Internal Medicine, Neurology, and Neurosurgery for patients with stroke and acute neurovascular conditions. Under resource-constrained conditions, the operational and economic impacts of the Neurovascular Unit were unknown. METHODS: Retrospective patient-level data was studied from two years prior and one year post NVU implementation. Descriptive statistical analysis and non-parametric testing were conducted on the acute length of stay (LOS), alternate level of care LOS, total cost per bed-day and per visit, and patient flow within each medical service and hospital wide. RESULTS: The median acute LOS per hospitalization for NVU-eligible patients decreased significantly (p=0.001). For Neurology patients, mean acute LOS decreased from 9.1 days pre-Neurovascular Unit to 7.6 days post and median acute LOS decreased from 6 to 5 days (p=0.002); however, mean alternate level of care LOS per visit more than doubled (from 1.6 to 4.1 days, p=0.001). For the Neurology service, the mean cost per visit decreased by $945, representing a 5% reduction (p=0.042) and the mean cost per bed-day decreased by $233, or 12.5% (p=0.026). Hospital wide, a saving of over C$450 000 was achieved. CONCLUSIONS: During the first year of operation, the NVU at TWH achieved decreased acute LOS per visit and lowered the total hospitalization cost per year for NVU-eligible patients. Addressing the issue of increased alternate level of care LOS could result in additional efficiencies.

Vessel wall magnetic resonance imaging in acute ischemic stroke: effects of embolism and mechanical thrombectomy on the arterial wall.

BACKGROUND AND PURPOSE: The aim of the study was to determine the effects of thromboembolism and mechanical thrombectomy on the vessel wall magnetic resonance imaging (VW-MRI) appearance of the intracranial arterial wall. METHODS: This was a cross-sectional study of consecutive patients with acute intracranial arterial occlusion who underwent high-resolution contrast-enhanced VW-MRI within days of stroke presentation. For each patient, we categorized arterial wall thickening and enhancement as definite, possible, or none using contralateral arteries as a reference standard. We performed χ(2) tests to compare the effects of medical therapy and mechanical thrombectomy. RESULTS: Sixteen patients satisfied inclusion criteria. Median time from symptom onset to VW-MRI was 3 days (interquartile range, 2 days). Among 6 patients treated with mechanical thrombectomy using a stent retriever, VW-MRI demonstrated definite arterial wall thickening in 5 (83%) and possible thickening in 1 (17%); there was definite wall enhancement in 4 (67%) and possible enhancement in 2 (33%). Among 10 patients treated with medical therapy alone, VW-MRI demonstrated definite arterial wall thickening in 3 (30%) and possible thickening in 2 (20%); there was definite wall enhancement in 2 (20%) and possible enhancement in 2 (20%). Arterial wall thickening and enhancement were more common in patients treated with mechanical thrombectomy than with medical therapy alone (P=0.037 and P=0.016, respectively). CONCLUSIONS: Mechanical thrombectomy results in intracranial arterial wall thickening and enhancement, potentially mimicking the VW-MRI appearance of primary arteritis. This arterial wall abnormality is less common in patients with arterial occlusion who have been treated with medical therapy alone.

Secondary Stroke Prevention in People With Schizophrenia.

BACKGROUND: People with schizophrenia are less likely than those without to be treated for cardiovascular disease. We aimed to evaluate the association between schizophrenia and secondary preventive care after ischemic stroke. METHODS AND RESULTS: In this retrospective cohort study, we used linked population-based administrative data to identify adults who survived 1 year after ischemic stroke hospitalization in Ontario, Canada between 2004 and 2017. Outcomes were screening, treatment, and control of risk factors, and receipt of outpatient physician services. We used modified Poisson regression to model the relative risk of each outcome among people with and without schizophrenia, adjusting for age and other factors. Among 81 163 people with ischemic stroke, 844 (1.04%) had schizophrenia. Schizophrenia was associated with lower rates of screening for hyperlipidemia (60.5% versus 66.0%, adjusted relative risk [aRR] 0.88 [95% CI, 0.84-0.93]) and diabetes (69.4% versus 73.9%, aRR 0.93 [95% CI, 0.89-0.97]), prescription of antihypertensive medications (91.2% versus 94.7%, aRR 0.96 [95% CI, 0.93-0.99]), achievement of target lipid levels (low-density lipoprotein <2 mmol/L) (30.6% versus 34.6%, aRR 0.86 [95% CI, 0.78-0.96]), and outpatient specialist visits (55.3% versus 67.8%, aRR 0.78 [95% CI, 0.74-0.83]) or primary care physician visits (94.5% versus 98.5%; aRR 0.96 [95% CI, 0.95-0.98]) within 1 year. There were no differences in prescription of antilipemic, antiglycemic, or anticoagulant medications, or in achievement of target hemoglobin A1c ≤7%. CONCLUSIONS: People with stroke and schizophrenia are less likely than those without to receive secondary preventive care. This may inform interventions to improve poststroke care and outcomes in those with schizophrenia.

Lifestyle approaches to hypertension for prevention of stroke and vascular cognitive impairment: a realist review protocol.

INTRODUCTION: Stroke and vascular cognitive impairment (VCI) are major global public health pandemics. The increased incidence of stroke and VCI is in part due to modifiable risk factors (MRFs), with hypertension (HTN) being the strongest single MRF. Even though the underlying causes of HTN are multifactorial, lifestyle choices (eg, poor diet, physical inactivity, alcohol consumption) are chief contributors. Lifestyle medicine (LSM) is a medical and evidence-based discipline that is a promising approach for preventing stroke and cognitive impairment, including VCI. The empirical evidence from systematic reviews, meta-analyses and large population-based studies has reported on the effectiveness of LSM interventions. However, the evaluation of such complex, social and behavioural interventions warrants more information to allow its successful implementation into innovative clinical care models. More importantly, we need to understand how such interventions work, who it works for and under what circumstances to successfully manage HTN and other MRFs (eg, hyperlipidaemia, smoking, alcohol use and diet). METHODS AND ANALYSIS: This realist review will follow the Realist and Meta-narrative Evidence Synthesis: Evolving Standards. The review will comprise four stages: (1) clarify the scope, (2) search for the evidence, (3) critically appraise primary studies and extract data focusing on the context, mechanism and outcome configuration and (4) synthesise evidence and draw conclusions. ETHICS AND DISSEMINATION: Research ethics board approval is not required for this review. The primary output of this review will be an evidence-based programme theory for LSM interventions for the management of HTN and other MRFs to reduce the risk of stroke and VCI. Findings from this review will be disseminated at three levels: micro (eg, patients, caregivers, clinicians, non-research partners), meso (eg, public, national not-for-profit organisations, professional associations and centres) and macro (eg, policymakers and government partners). PROSPERO REGISTRATION NUMBER: CRD42024511566.

Hospital outbreak of the severe acute respiratory coronavirus virus 2 (SARS-CoV-2) delta variant in partially and fully vaccinated patients and healthcare workers in Toronto, Canada.

The severe acute respiratory coronavirus virus 2 (SARS-CoV-2) delta variant is highly transmissible, and current vaccines may have reduced effectiveness in preventing symptomatic infection. Using epidemiological and genomic analyses, we investigated an outbreak of the variant in an acute-care setting among partially and fully vaccinated individuals. Effective outbreak control was achieved using standard measures.