FIND Stroke Recovery Study (FIND): rationale and protocol for a longitudinal observational cohort study of trajectories of recovery and biomarkers poststroke.

INTRODUCTION: Comprehensive studies mapping domain-specific trajectories of recovery after stroke and biomarkers reflecting these processes are scarce. We, therefore, initiated an exploratory prospective observational study of stroke cases with repeated evaluation, the FIND Stroke Recovery Study. We aim to capture trajectories of recovery from different impairments, including cognition, in combination with broad profiling of blood and imaging biomarkers of the recovery. METHODS AND ANALYSIS: We recruit individuals with first-ever stroke at the stroke unit at the Sahlgrenska University Hospital, Sweden, to FIND. The inclusion started early 2018 and we aim to enrol minimum 500 patients. Neurological and cognitive impairments across multiple domains are assessed using validated clinical assessment methods, advanced neuroimaging is performed and blood samples for biomarker measuring (protein, RNA and DNA) at inclusion and follow-up visits at 3 months, 6 months, 1 year, 2 years and 5 years poststroke. At baseline and at each follow-up visit, we also register clinical variables known to influence outcomes such as prestroke functioning, stroke severity, acute interventions, rehabilitation, other treatments, socioeconomic status, infections (including COVID-19) and other comorbidities. Recurrent stroke and other major vascular events are identified continuously in national registers. ETHICS AND DISSEMINATION: FIND composes a unique stroke cohort with detailed phenotyping, repetitive assessments of outcomes across multiple neurological and cognitive domains and patient-reported outcomes as well as blood and imaging biomarker profiling. Ethical approval for the FIND study has been obtained from the Regional Ethics Review Board in Gothenburg and the Swedish Ethics Review Board. The results of this exploratory study will provide novel data on the time course of recovery and biomarkers after stroke. The description of this protocol will inform the stroke research community of our ongoing study and facilitate comparisons with other data sets. TRIAL REGISTRATION NUMBER: The protocol is registered at http://www. CLINICALTRIALS: gov, Study ID: NCT05708807.

Association of the COVID-19 pandemic on stroke admissions and treatment globally: a systematic review.

OBJECTIVES: The COVID-19 pandemic has highlighted insufficiencies and gaps within healthcare systems globally. In most countries, including high-income countries, healthcare facilities were over-run and occupied with too few resources beyond capacity. We carried out a systematic review with a primary aim to identify the influence of the COVID-19 pandemic on the presentation and treatment of stroke globally in populations≥65 years of age. DESIGN: A systematic review was completed. In total, 38 papers were included following full-text screening. DATA SOURCES: PubMed, MEDLINE and Embase. ELIGIBILITY CRITERIA: Eligible studies included observational and real-world evidence publications with a population who have experienced stroke treatment during the COVID-19 pandemic. Exclusion criteria included studies comparing the effect of the COVID-19 infection on stroke treatment and outcomes. DATA EXTRACTION AND SYNTHESIS: Primary outcome measures extracted were the number of admissions, treatment times and patient outcome. Secondary outcomes were severity on admission, population risk factors and destination on discharge. No meta-analysis was performed. RESULTS: This review demonstrated that 84% of studies reported decreased admissions rates during the COVID-19 pandemic. However, among those admitted, on average, had higher severity of stroke. Additionally, in-hospital stroke treatment pathways were affected by the implementation of COVID-19 protocols, which resulted in increased treatment times in 60% of studies and increased in-hospital mortality in 82% of studies by 100% on average. The prevalence of stroke subtype (ischaemic or haemorrhagic) and primary treatment methods (thrombectomy or thrombolysis) did not vary due to the COVID-19 pandemic. CONCLUSIONS: During the COVID-19 pandemic, many populations hesitated to seek medical attention, decreasing hospital admissions for less severe strokes and increasing hospitalisation of more severe cases and mortality. The effect of the pandemic on society and healthcare systems needs to be addressed to improve stroke treatment pathways and prepare for potential future epidemics. PROSPERO REGISTRATION NUMBER: CRD42021248564.

RETurn to work After stroKE (RETAKE) Trial: protocol for a mixed-methods process evaluation using normalisation process theory.

OBJECTIVES: This mixed-method process evaluation underpinned by normalisation process theory aims to measure fidelity to the intervention, understand the social and structural context in which the intervention is delivered and identify barriers and facilitators to intervention implementation. SETTING: RETurn to work After stroKE (RETAKE) is a multicentre individual patient randomised controlled trial to determine whether Early Stroke Specialist Vocational Rehabilitation (ESSVR) plus usual care is a clinically and cost-effective therapy to facilitate return to work after stroke, compared with usual care alone. This protocol paper describes the embedded process evaluation. PARTICIPANTS AND OUTCOME MEASURES: Intervention training for therapists will be observed and use of remote mentor support reviewed through documentary analysis. Fidelity will be assessed through participant questionnaires and analysis of therapy records, examining frequency, duration and content of ESSVR sessions. To understand the influence of social and structural contexts, the process evaluation will explore therapists' attitudes towards evidence-based practice, competency to deliver the intervention and evaluate potential sources of contamination. Longitudinal case studies incorporating non-participant observations will be conducted with a proportion of intervention and usual care participants. Semistructured interviews with stroke survivors, carers, occupational therapists, mentors, service managers and employers will explore their experiences as RETAKE participants. Analysis of qualitative data will draw on thematic and framework approaches. Quantitative data analysis will include regression models and descriptive statistics. Qualitative and quantitative data will be independently analysed by process evaluation and Clinical Trials Research Unit teams, respectively. Linked data, for example, fidelity and describing usual care will be synthesised by comparing and integrating quantitative descriptive data with the qualitative findings. ETHICS AND DISSEMINATION: Approval obtained through the East Midlands-Nottingham 2 Research Ethics Committee (Ref: 18/EM/0019) and the National Health ServiceResearch Authority. Dissemination via journal publications, stroke conferences, social media and meetings with national Stroke clinical leads. TRIAL REGISTRATION NUMBER: ISRCTN12464275.

Hyperacute stroke thrombolysis via telemedicine: a multicentre study of performance, safety and clinical efficacy.

OBJECTIVES: Timely thrombolysis of ischaemic stroke improves functional recovery, yet its delivery nationally is challenging due to shortages in the stroke specialist workforce and large geographical areas. One solution is remote stroke specialist input to regional centres via telemedicine. This study evaluates the usage and key metrics of performance of the East of England Stroke Telemedicine Partnership-the largest telestroke service in the UK-in providing hyperacute stroke care. DESIGN: Prospective observational study. SETTING: The East of England Stroke Telemedicine Partnership provides a horizontal 'hubless' model of out-of-hours hyperacute stroke care to a population of 6.2 million across a 7500 square mile semirural region. PARTICIPANTS: All (2709) telestroke consultations between 1 January 2014 and 31 December 2019. MAIN OUTCOME MEASURES: Thrombolysis decision, pre-thrombolysis and post-thrombolysis stroke severity (National Institutes of Health Stroke Scale, NIHSS), haemorrhagic complications, and hyperacute pathway timings. RESULTS: Over the period, 1149 (42.4%) individuals were thrombolysed. Thrombolysis rates increased from 147/379 (38.8%) in 2014 to 225/490 (45.9%) in 2019. Median (IQR) pre-thrombolysis NIHSS was 10 (6-17), reducing to 6 (2-14) 24-hour post-thrombolysis (p<0.001). Post-thrombolysis haemorrhage occurred in 27 cases (2.3%). Over the period, median (IQR) door-to-needle time reduced from 85 (65-108) min to 68 (55-97.5) min (p<0.01), driven by improved imaging-to-needle times from 52.5 (38-72.25) min to 42 (30.5-62.5) min (p<0.01). However, the same period saw an increase in median onset-to-hospital arrival time from 77.5 (60-109.25) min to 95 (70-135) min (p<0.001). CONCLUSIONS: The results from this large hyperacute telestroke cohort indicate two important points for clinical practice. First, telemedicine via a hubless horizontal model provides a clinically effective and safe method for delivering hyperacute stroke thrombolysis. Second, improved door-to-needle times were offset by a concerning rise in prehospital timings. These findings indicate that although telemedicine may benefit in-hospital hyperacute stroke care, improvements across the whole stroke pathway are essential.

Study protocol for a phase II randomised, double-blind, placebo-controlled trial of perampanel as an antiepileptogenic treatment following acute stroke.

INTRODUCTION: Stroke is a common cause of epilepsy that may be mediated via glutamate dysregulation. There is currently no evidence to support the use of antiseizure medications as primary prevention against poststroke epilepsy. Perampanel has a unique antiglutamatergic mechanism of action and may have antiepileptogenic properties. This study aims to evaluate the efficacy and safety of perampanel as an antiepileptogenic treatment in patients at high risk of poststroke epilepsy. METHODS AND ANALYSIS: Up to 328 patients with cortical ischaemic stroke or lobar haemorrhage will be enrolled, and receive their first treatment within 7 days of stroke onset. Patients will be randomised (1:1) to receive perampanel (titrated to 6 mg daily over 4 weeks) or matching placebo, stratified by stroke subtype (ischaemic or haemorrhagic). Treatment will be continued for 12 weeks after titration. 7T MRI will be performed at baseline for quantification of cerebral glutamate by magnetic resonance spectroscopy and glutamate chemical exchange saturation transfer imaging. Blood will be collected for measurement of plasma glutamate levels. Participants will be followed up for 52 weeks after randomisation.The primary study outcome will be the proportion of participants in each group free of late (more than 7 days after stroke onset) poststroke seizures by the end of the 12-month study period, analysed by Fisher's exact test. Secondary outcomes will include time to first seizure, time to treatment withdrawal and 3-month modified Rankin Scale score. Quality of life, cognitive function, mood and adverse events will be assessed by standardised questionnaires. Exploratory outcomes will include correlation between cerebral and plasma glutamate concentration and stroke and seizure outcomes. ETHICS AND DISSEMINATION: This study was approved by the Alfred Health Human Research Ethics Committee (HREC No 44366, Reference 287/18). TRIAL REGISTRATION NUMBER: ACTRN12618001984280; Pre-results.

Cardiovascular and cerebrovascular health after pre-eclampsia: the Motherhealth prospective cohort study protocol.

INTRODUCTION: Cardiovascular and cerebrovascular diseases (CCVDs) are the leading cause of maternal mortality in the first year after delivery. Women whose pregnancies were complicated by pre-eclampsia are at particularly high risk for adverse events. In addition, women with a history of pre-eclampsia have higher risk of CCVD later in life. The physiological mechanisms that contribute to increased CCVD risk in these women are not well understood, and the optimal clinical pathways for postpartum CCVD risk reduction are not yet defined. METHODS AND ANALYSIS: The Motherhealth Study (MHS) is a prospective cohort study at Columbia University Irving Medical Center (CUIMC), a quaternary care academic medical centre serving a multiethnic population in New York City. MHS began recruitment on 28 September 2018 and will enrol 60 women diagnosed with pre-eclampsia with severe features in the antepartum or postpartum period, and 40 normotensive pregnant women as a comparison cohort. Clinical data, biospecimens and measures of vascular function will be collected from all participants at the time of enrolment. Women in the pre-eclampsia group will complete an additional three postpartum study visits over 12-24 months. Visits will include additional detailed cardiovascular and cerebrovascular phenotyping. As this is an exploratory, observational pilot study, only descriptive statistics are planned. Data will be used to inform power calculations for future planned interventional studies. ETHICS AND DISSEMINATION: The CUIMC Institutional Review Board approved this study prior to initiation of recruitment. All participants signed informed consent prior to enrolment. Results will be disseminated to the clinical and research community, along with the public, on completion of analyses. Data will be shared on reasonable request.

Decreasing referrals to transient ischaemic attack clinics during the COVID-19 outbreak: results from a multicentre cross-sectional survey.

OBJECTIVE: The COVID-19 pandemic is having major implications for stroke care with a documented significant fall in hospital acute stroke admissions. We investigated whether COVID-19 has resulted in a decreased number of referrals to the transient ischaemic attack (TIA) clinics across the North West London region. SETTING AND DESIGN: All the TIA clinical leads of the North West London region received an invitation by email to participate in an online survey in May 2020. The survey questionnaire aimed to assess the number of patients with suspected TIA consecutively referred to each of the TIA clinics of the North West London region between 1 March and 30 April 2020, the COVID-19 period, and between 1 March and 30 April 2019. RESULTS: We had a response rate of 100%. During the COVID-19 period, the TIA clinics of the North West London region received 440 referrals compared with 616 referrals received between 1 March and 30 April 2019 with a fall in the number of the referrals by 28.6%. In April 2020 compared with April 2019, the number of the referrals declined by 40.1%. CONCLUSIONS: This multicentre analysis documented a significant reduction in the number of patients referred with suspected TIA to the specialised rapid access outpatient clinics in the North West London region during the COVID-19 pandemic. Future studies are needed to confirm our findings and to better characterise the incidence of cerebrovascular disease during the COVID-19 pandemic.