Indirect Effects of Operating a Mobile Stroke Treatment Unit

Stroke, Volume 56, Issue 6, Page 1646-1649, June 1, 2025. Mobile stroke units, also referred to as mobile stroke treatment units, have revolutionized acute stroke care by reducing thrombolysis and mechanical thrombectomy times, resulting in positive patient outcomes. These direct benefits of mobile stroke treatment units have been well documented in the literature. Yet, despite these demonstrated benefits, mobile stroke treatment unit programs are often perceived as a costly financial burden to establish. However, when implemented effectively, Mobile stroke programs can yield indirect societal and institutional benefits. We highlight the indirect effects and factors that are less commonly reported when operating a mobile stroke program, including aiding local emergency medical services, improving emergency department stroke care and throughput, optimizing hospital resource utilization, and extending community education and outreach initiatives.

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American Heart Association Standards for Postacute Stroke Rehabilitation Care

Stroke, Volume 56, Issue 6, Page 1650-1654, June 1, 2025. Evidence-based rehabilitation and secondary prevention interventions improve poststroke functional recovery and reduce secondary complications. However, stroke rehabilitation expertise, processes of care, and educational resources vary among sites where postacute care (PAC) is delivered. The American Heart Association developed quality standards based on the American Heart Association 2016 Guidelines for Adult Stroke Rehabilitation and Recovery to address these gaps. An interdisciplinary PAC standards writing committee identified key areas for PAC: quality improvement, medical management, care coordination, patient/caregiver and personnel education, and program management. Subgroups developed draft standards, combining results from a national landscape survey of PAC sites with clinical practice guidelines. The committee then refined the draft standards using a consensus-based process. American Heart Association staff and PAC sites in Montana convened a learning collaborative to gather feedback and provide gap analyses of the standards relative to current practices. Qualitative input from beta testing in Montana and quantitative results from the nationwide survey and Montana sites were analyzed and used to refine the standards further. The national landscape survey demonstrated that most sites do not meet the proposed standards: stroke program oversight structure (78% fall short), stroke rehabilitation leadership (70%), stroke-specific order sets/protocols (61%), and policies requiring staff stroke education (66%). Regarding Montana findings, 41% of the PAC sites have no mechanisms to identify areas of quality improvement specific to their stroke rehabilitation programs, and 59% do not use standardized tools to ensure that performance improvement initiatives are followed. However, with adequate support and resources, most Montana sites stated that they would be able to meet the proposed standards. We conclude that the Stroke PAC Quality Standards are applicable in PAC settings and provide a pathway to improving access to high-quality care for stroke survivors. Outcome studies are needed to confirm anticipated improvements in medical and functional outcomes.

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STAY-HOME: Endovascular Thrombectomy for Patients With Prestroke Disability

Stroke, Volume 56, Issue 6, Page 1642-1645, June 1, 2025. Thrombectomy significantly improves clinical outcomes in patients with large vessel occlusion. However, the foundational trials used restrictive criteria, excluding patients with prestroke disability and included a few elderly patients ( >80 years old). In addition, results from registries demonstrated conflicting results. We propose that there is equipoise for the elderly and prestroke disability to undergo thrombectomy and that trials are urgently required to guide treatment.

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Endovascular Therapy for Late-Window M2-Segment Middle Cerebral Artery Occlusion: Analysis of the CLEAR Study

Stroke, Ahead of Print. BACKGROUND:There is uncertainty about whether patients with M2 occlusion benefit from endovascular therapy (EVT) in the late (6–24-hour) time window. We evaluated the clinical outcomes of patients with M2 occlusion selected for EVT compared with those who received medical management (MM) in the late window.METHODS:This multinational cohort study was conducted at 66 sites across 10 countries (January 2014 to May 2022). We included consecutive patients with late-window stroke due to M2 occlusion, baseline National Institutes of Health Stroke Scale score of ≥5, and premorbid modified Rankin Scale score of ≤2 who received EVT or MM alone. The primary end point was 90-day ordinal shift in the modified Rankin Scale score. Safety end points were symptomatic intracranial hemorrhage and 90-day mortality. Differences in outcomes were determined using inverse probability of treatment weighting–adjusted logistic regression models.RESULTS:Among 5098 patients, 496 met inclusion criteria (median [interquartile range] age, 74 years [62–81 years]; baseline National Institutes of Health Stroke Scale score, 12 [8–17]), of whom 394 (79.4%) received EVT and 102 (20.6%) MM. In inverse probability of treatment weighting adjusted analyses, there was no favorable 90-day ordinal modified Rankin Scale shift (odds ratio, 1.39 [95% CI, 0.92–2.12]) and no difference of functional independence rates (modified Rankin Scale score of 0–2; odds ratio, 1.72 [95% CI, 0.93–3.15]) with EVT compared with MM. Moreover, symptomatic intracranial hemorrhage risk (odds ratio, 3.46 [95% CI, 0.50–23.92]) and 90-day mortality (odds ratio, 1.11 [95% CI, 0.66–1.87]) were not statistically different between treatment groups.CONCLUSIONS:In patients with M2 occlusion in the 6- to 24-hour time window, there was no difference in disability outcomes or symptomatic intracranial hemorrhage risk between patients treated with EVT compared with MM. Results of ongoing randomized trials will provide further insight.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT04096248.

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Biofeedback Training for 3-Dimensional Finger Force Control to Improve Upper Limb Function Poststroke: An RCT

Stroke, Ahead of Print. BACKGROUND:After stroke, impairment of hand sensorimotor control leads to improperly scaled and directed fingertip forces that disrupt object manipulation. The objective of this study was to determine the efficacy of finger force magnitude and direction training using 3-dimensional versus 1-dimensional biofeedback to enhance poststroke upper extremity motor recovery.METHODS:A double-blind randomized controlled trial took place in the Veterans Affairs laboratory from 2020 to 2023. Forty-five stroke survivors were randomly assigned to the experimental or control group. Both groups received 18 training sessions to generate digit force in the target magnitude and direction. The experimental group trained with visual feedback on the digit force magnitude in 3 dimensions. The control group trained with 1-dimensional visual feedback on the digit force magnitude along the target direction only. The primary outcome was the change in upper extremity function assessed using the Action Research Arm Test post-intervention.RESULTS:Baseline characteristics were comparable between the groups (mean age, 59 years, 60% male, 40% Black). The change between pretraining and posttraining Action Research Arm Test scores was significantly greater for the experimental group than for the control group (experimental mean, 3.5 [CI, 2.2–4.8] versus control mean, 0.8 [CI, −0.5 to 2.1];P=0.005). This difference was maintained at 1-month follow-up. Secondary analysis showed that individuals in the experimental group whose stroke occurred within a year prior improved more (mean, 6.1 [CI, 4.0–8.3]) than others (P

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Innovative Hydrogel-Based Treatments for Neonatal Stroke

Stroke, Ahead of Print. Neonatal stroke, occurring within the first 28 days after birth, affects >1 in every 2500 newborns. The weekly adjusted risk of stroke in a term newborn is 3-fold greater than for a male smoker aged 50 to 59 years with diabetes and hypertension. Neonatal stroke has profound clinical and socioeconomic implications, causing cerebral palsy, epilepsy, and various motor, sensory, and cognitive disabilities. Currently, there is no treatment for the brain damage that neonatal stroke causes. Hydrogels, with their tunable elasticity and stiffness, shear-thinning properties, and ability to deliver therapeutic agents locally in a controlled manner, offer significant potential for tissue repair and regeneration. In this review, we synthesize the current knowledge on biocompatible hydrogels, providing insights into how they can be engineered to address the pathophysiology of neonatal stroke and their previous use in repairing severe focal lesions in the adult central nervous system. By exploring cutting-edge hydrogel therapies, this review aims to provide a comprehensive perspective on the potential of hydrogel therapy to improve outcomes for infants suffering from severe brain injury due to neonatal stroke.

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Preferences for long-termcare among elderly patients who had a stroke with disabilities in Eastern China: protocol for a ditscrete choice experiment study

Background
Stroke is a leading cause of disability among older adults worldwide, often resulting in significant physical, cognitive and emotional impairments that require long-term care. With ageing populations and increasing stroke prevalence, the demand for appropriate and sustainable long-term care is growing. However, designing care models that align with the complex needs and preferences of elderly patients who had a stroke remains a challenge. This study employs a discrete choice experiment (DCE) to measure and quantify patients’ preferences for long-term care. The primary objectives of this study are as follows: (1) identify and examine the key attributes and levels of long-term care that are most valued by this patient population, (2) assess patients’ preferences for long-term care and explore the role of each attribute on overall preference and (3) explore heterogeneity in preferences based on participants’ characteristics through subgroup analyses.

Methods
The research was conducted in accordance with the design programme of the DCE study. Seven attributes were developed through a systematic literature review, in-depth interviews and experts consultation. A partial factorial survey design was generated through an orthogonal experimental design to optimise the choice scenario sets. We plan to conduct a DCE questionnaire survey in Suzhou, Jiangsu Province, China, and recruit at least 500 participants. The final data will be analysed through a mixed logit model and a latent class model to explore the preference of elderly patients who had a stroke with disabilities for long-term care.

Ethics and dissemination
This study was approved by the Ethics Committee of Nanjing Medical University-Affiliated Suzhou Hospital (K-2024-096 K01). All participants will be required to provide informed consent. The findings of this study will be disseminated and shared with interested patient groups and the general public through a variety of channels, including online blogs, policy briefs, national and international conferences, and peer-reviewed journals.

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Fibrinogen Depletion Coagulopathy and Hemorrhagic Transformation in Acute Ischemic Stroke Treated With Bridging Therapy

Stroke, Ahead of Print. BACKGROUND:Hemorrhagic transformation (HT) frequently occurs in acute ischemic stroke patients with a large vessel occlusion undergoing endovascular therapy (EVT), significantly impacting functional outcomes. We aimed to determine whether an early fibrinogen depletion coagulopathy (FDC) was associated with HT following bridging therapy (ie,intravenous thrombolysis [IVT] followed by EVT), and to identify its associated factors.METHODS:We retrospectively analyzed prospectively collected data from 296 patients with acute ischemic stroke with a large vessel occlusion who underwent EVT alone or bridging therapy, with fibrinogen levels measured both before baseline imaging and at the start of the EVT procedure. FDC was defined as a fibrinogen level 1.0 g/L from baseline. The primary outcome was the occurrence of any HT at 24 to 36 hours. Secondary outcomes included symptomatic HT, parenchymal hematomas, and 3-month mortality. The relationships between FDC and outcomes were studied using multivariable logistic regression analyses, adjusting for relevant confounders. We also studied baseline characteristics associated with FDC occurrence.RESULTS:Of the 296 patients enrolled, 102 (34.5%) experienced HT, and 54 (18.2%) developed FDC. FDC was strongly associated with IVT use (53/161 [32.9%] versus 1/135 [0.7%] in IVT-treated and non-IVT-treated patients, respectively;P

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Anticoagulation Timing in Acute Stroke With Atrial Fibrillation According to Chronic Kidney Disease: The OPTIMAS Trial

Stroke, Ahead of Print. INTRODUCTION:Patients with chronic kidney disease (CKD) are at increased risk of ischemic stroke (IS) and intracerebral hemorrhage, so the safety and efficacy of early direct oral anticoagulant (DOAC) initiation in those with CKD are of interest.METHODS:OPTIMAS was a multicenter, randomized, parallel-group, open-label trial with blinded outcome assessment, recruiting patients with IS and atrial fibrillation from 100 UK hospitals between 2019 and 2024. Participants were randomized 1:1, stratified by stroke severity, to early (within 4 days of onset) or delayed (at days 7–14) DOAC initiation. CKD was defined as a past medical history of known CKD, collected according to trial protocol as part of the case report form. For this prespecified subgroup analysis, the trial cohorts were classified according to the presence or absence of CKD. Whether CKD modified the treatment effect of early DOAC initiation was determined by fitting mixed effects logistic regression models with interaction terms between CKD and treatment group. The primary outcome was a composite outcome of recurrent IS, symptomatic intracranial hemorrhage, and systemic arterial embolism. Key secondary outcomes included the individual components of the primary outcome and all-cause mortality.RESULTS:We included 3601 patients (mean age, 78±10 years; 45% female), 543 with CKD. There were 116 primary outcome events: 97 (3.2%) in the normal kidney function group and 19 (3.5%) in the CKD group. There was no difference between early and delayed DOAC initiation for the primary outcome in either the normal kidney function group (odds ratio, 1.01 [95% CI, 0.67–1.51]) or the CKD group (odds ratio, 0.90 [95% CI, 0.36–2.25];Pinteraction=0.822). Similarly, for the secondary outcomes, we detected no modification of the treatment effect according to CKD (Pinteractionvalues of 0.637, 0.386, and 0.107 for IS, symptomatic intracranial hemorrhage, and all-cause mortality, respectively).CONCLUSIONS:Our findings suggest that CKD does not modify the effects of early versus delayed DOAC initiation after acute IS. Based on these results, early DOAC initiation should not be withheld in patients with CKD.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03759938.

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Prior Reperfusion Strategy Does Not Modify Outcome in Early Versus Late Start of Anticoagulants in Patients With Ischemic Stroke: Prespecified Subanalysis of the Randomized Controlled ELAN Trial

Stroke, Ahead of Print. BACKGROUND:Early initiation of direct oral anticoagulants (DOACs) in patients with nonvalvular atrial fibrillation and acute ischemic stroke is beneficial and safe. Whether prior acute reperfusion therapy modifies the treatment effect of early versus late DOAC initiation is unknown.METHODS:For this post hoc analysis of the multicenter, randomized controlled ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Post-Ischaemic Stroke Patients With Atrial Fibrillation), all participants with data concerning reperfusion treatment were included. The primary outcome was the composite outcome of recurrent ischemic stroke, symptomatic intracranial hemorrhage, major extracranial bleeding, systemic embolism, or vascular death within 30 days. Patients were divided into 4 groups based on prior reperfusion therapy: no treatment, intravenous thrombolysis (IVT), endovascular treatment (EVT), or IVT combined with EVT. We performed logistic regression adjusted for age, hypertension, infarct location/size, pre-modified Rankin Scale, NIHSS, and hemorrhagic transformation, including the interaction term between treatment groups (early versus late DOAC) and reperfusion strategy.RESULTS:We included 1973 of 2013 (98%) patients of the ELAN trial population, with a median age of 77 (71–84) years and of whom 899 (46%) were female. Of them, 1015 (51%) underwent no prior reperfusion treatment, 519 (26%) IVT, 190 (10%) EVT, and 249 (13%) IVT+EVT. We did not identify an interaction for any of the outcome events between prior reperfusion therapy and timing of DOAC initiation. Rates were numerically lower in the early DOAC-initiated group for the following: no reperfusion therapy, 17 (3.3%) versus 24 (4.8%; adjusted odds ratio, 0.69 [95% CI, 0.36–1.28]); EVT, 1 (1.2%) versus 7 (6.4%; adjusted odds ratio, 0.25 [95% CI, 0.03–1.21]); and EVT+IVT, 3 (2.4%) versus 4 (3.3%; adjusted odds ratio, 0.76 [95% CI, 0.17–3.23]). In patients who had received IVT, the rates were 3% (n=8) in the early group versus 2% (n=5) in the late group (adjusted odds ratio, 1.52 [95% CI, 0.52–4.84]).CONCLUSIONS:Prior reperfusion therapy does not modify the effect of early versus late DOAC initiation on clinical outcomes in patients with atrial fibrillation and acute ischemic stroke.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03148457.

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Enhancing dyadic outcomes of stroke survivors and caregivers: protocol for a randomised controlled trial

Introduction
Stroke is a leading cause of death and disability worldwide. Stroke survivors and their caregivers often face profound social isolation and various participation restrictions, resulting in frustration and adverse health outcomes. Dyad-focused interventions, which address both survivor and caregiver needs, are essential during the transition process. However, few interventions equally prioritise the outcomes of both survivors and caregivers. This study aims to evaluate the efficacy of a newly developed dyad-focused strategy training intervention in enhancing participation among stroke survivors and their caregivers.

Methods and analysis
This study employs a single-blind, parallel-group randomised controlled trial with allocation concealment and assessor blinding. We aim to enrol 138 stroke survivor-caregiver dyads, randomly assigned in a 1:1 ratio to either the experimental intervention group or the control group. Both groups will receive their usual rehabilitation plus 45–60 min sessions of the intervention twice weekly for a total of 12 sessions. Outcome measures, including the Participation Measure-3 Domains, 4 Dimensions, General Self-Efficacy Scale and Activity Measure for Post-Acute Care, will be collected at baseline, post-intervention and at 3-month, 6-month and 12-month follow-ups. Data will be analysed using multiple linear regression and mixed-effects regression models. Qualitative indepth interviews with participants, caregivers and therapists will be conducted post intervention, transcribed and thematically analysed.

Ethics and dissemination
Ethics approval was obtained from the Ethics Committee of Taipei Medical University (approval number: N202203083), National Taiwan University Hospital (approval number: 202207096RINA) and Taipei Tzu Chi Hospital (approval number: 11 M-107). Findings will be disseminated through presentations at scientific conferences and publications in peer-reviewed journals.

Trial registration number
NCT05571150; Preresults.

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Genetic Risk Scores in Stroke Research and Care

Stroke, Ahead of Print. Stroke remains a leading cause of death and disability worldwide. While well-established risk factors play a major role, genetic predisposition is a crucial determinant of stroke susceptibility, with heritability estimates up to 39% for ischemic stroke and 29% for intracerebral hemorrhage. Advances in next-generation sequencing and genome-wide association studies have identified numerous genetic loci associated with stroke risk, paving the way for the development of genetic risk scores. These scores aggregate information from multiple genetic variants to estimate an individual’s stroke risk, offering a promising tool for personalized risk stratification that complements traditional clinical models. While GRSs have demonstrated strong predictive potential for primary stroke events in population-based settings, their integration into clinical practice remains limited. Emerging evidence suggests that GRSs could add value in clinical decision-making, for instance, for stratifying ischemic stroke risk in patients with atrial fibrillation, assessing intracerebral hemorrhage risk in anticoagulant users, and predicting vascular risk factor control in stroke survivors. The incorporation of GRSs with multiomics data and machine learning may further refine risk assessment, driving personalized prevention strategies for both primary and secondary stroke preventions. A major challenge is the limited applicability of GRS across diverse populations, as most genome-wide association studies have been conducted in individuals of European ancestry. Addressing this limitation is critical for ensuring equitable and effective implementation of GRSs in clinical settings. As methodologies continue to evolve, integrating GRS into stroke research could significantly enhance risk assessment and support precision medicine approaches tailored to individual patients.

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Sex Differences in the Neurovascular Health of Aging Adults

Stroke, Ahead of Print. BACKGROUND:Poor cerebrovascular reactivity is associated with a higher risk of cerebrovascular disease. The most common method to study cerebrovascular reactivity in aging adults, transcranial Doppler ultrasound, yields measurements in large intracranial arteries, but not in regional brain parenchyma that may be more impaired in some disease processes. Measurements derived from transcranial Doppler ultrasound suggest that there are sex differences in cerebrovascular reactivity for aging adults. We investigated the association between age and sex on cerebrovascular reactivity using blood oxygen level dependent (BOLD) magnetic resonance imaging in a representative group of aging adults.METHODS:This cross-sectional study investigated BOLD cerebrovascular reactivity to CO2in a representative group of aging adults, 51 to 83 years old. We manipulated end-tidal carbon dioxide with breathing exercises and evaluated changes in 6 brain regions: whole brain, white matter, cortical gray matter, subcortical gray matter, left hippocampus, and right hippocampus. We used 1 linear regression per region to investigate the effects of age, sex, and their interaction on BOLD cerebrovascular reactivity.RESULTS:We report an age-by-sex interaction for all brain regions (P≤0.050), except cortical gray matter (P=0.062). For white matter and subcortical gray matter, female participants trended toward an age-related BOLD cerebrovascular reactivity increase (P≤0.058), while male participants did not change with age (P >0.580). In the whole brain and bilateral hippocampi, the age trends for each sex were in opposite directions but not significant (P >0.211). We report a main effect of sex (female greater than male participants) for subcortical gray matter and the right hippocampus (P≤0.048) and no main effect of age in any model.CONCLUSIONS:We present the first report of age-related BOLD cerebrovascular reactivity increases in older female participants and higher BOLD cerebrovascular reactivity in older female compared with male participants. Sex and age-by-sex-based differences seem to be driven by changes in white matter, subcortical gray matter, and bilateral hippocampi.

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