Stroke is one of the top causes of disability in Malaysia, yet caregivers have limited access to structured, culturally tailored education to support poststroke care.

To develop and validate the CaknaStrok Education Package (CEP), a blended learning intervention comprising a printed guidebook and a trilingual mobile health application for informal stroke caregivers in Malaysia.

Methodological study involving the development and validation of a caregiver education programme guided by the Analyse, Design, Develop, Implement, Evaluate (ADDIE) instructional design framework.

Development and validation were conducted in Malaysia between January 2022 and December 2023. Both experts and caregivers were recruited from two tertiary hospitals on the East Coast of Malaysia, with caregivers identified from inpatient wards and outpatient clinics at these hospitals.

Content validation involved 10 multidisciplinary experts. Face validation involved 14 informal stroke caregivers who met eligibility criteria, and all completed the study.

CEP was developed based on prior needs assessment and expert input. Content validation was undertaken using the Content Validity Index (CVI) and face validation using the Face Validity Index (FVI), both assessed on a four-point Likert scale. Qualitative feedback was also obtained from the participants.

CEP consists of six modules delivered via a printed guidebook and a trilingual app with videos, assessment tools and local resources. Experts rated the content highly valid (Scale-level (S)-CVI/the average method (Ave): 0.97–0.99 across domains). Caregivers reported strong acceptability (S-FVI/Ave: 0.95–0.99). Qualitative feedback from experts and caregivers informed refinements to content clarity, usability and presentation, including improved navigation, consistent language use and enhanced visual design. Suggestions requiring substantial structural changes were documented for future iterations.

The CEP shows strong content and face validity as a blended caregiver education tool. By combining printed and digital formats, CEP addresses cultural and access challenges and provides a scalable model for stroke caregiver education in Malaysia. Further pilot or feasibility studies are warranted to evaluate usability, engagement and implementation in real-world settings prior to effectiveness evaluation.

Anxiety is a common non-motor symptom of Parkinson’s disease (PD). There is no specific pharmacological intervention for people with PD who experience anxiety. Current non-pharmacological treatments have mixed or inconclusive results and there does not appear to be a non-pharmacological intervention for people with PD disease and anxiety that focuses on activity and participation.

To co-produce an occupation-focused complex intervention to help people with PD live well with anxiety that community-based occupational therapists can deliver.

Six-stage complex intervention development was conducted using online logic modelling and a participatory approach to organise the new intervention’s key inputs, processes and outcomes important to people with PD living with anxiety.

Data were collected via online logic modelling sessions involving people with Parkinson’s, care partners and occupational therapists across the UK from April 2022 to June 2022.

34 participants were recruited (people with PD n=14, care partners n=9, occupational therapists n=11) for the online logic modelling sessions.

Resources to support the new intervention (‘inputs’) include adequate resourcing, education for professionals and people with PD, flexibility of delivery methods and goal setting. The intervention’s actions to produce outcomes (‘processes’) should include 1:1 support, lifestyle management, providing meaningful information, collaborative goal setting, therapeutic use of everyday activities, and involvement of friends and families. The intended results (‘outcomes’) should include a reduction in anxiety symptoms, people with PD enjoying more meaningful activities, increased understanding of anxiety and PD, improvement in clinical outcomes and improvement of service-level outcomes. These key aspects were incorporated into an intervention manual, educational material and training video.

We have systematically coproduced a new occupation-focused complex intervention to help people with PD to live well with anxiety. This provides the basis for the next project in which this intervention will be tested for feasibility.

ISRCTN62762494.

The study evaluated the feasibility and efficacy of a non-immersive virtual reality (VR) system on upper extremity (UE) recovery in ischaemic stroke patients in comparison to a conventional physiotherapy.

An open-label, parallel-group, randomised controlled trial randomly assigned the participants to two groups, VR intervention or conventional physiotherapy.

Two tertiary stroke care centres in South India participated in the study.

Sixty first-ever ischaemic stroke patients (1–6 months of stroke onset) having spasticity grades of 1 or 1+ as per Modified Ashworth scale and Brunnstrom recovery stages of 3, 4 or 5 in the UE were included in the intention-to-treat analysis.

High-intensity non-immersive VR-based comprehensive rehabilitation gaming system with a duration of 12 weeks (3 days/week) was compared with equally intensive conventional physiotherapy.

The feasibility outcome was the compliance with the treatment. The primary efficacy outcome was the improvement in the motor function assessed by the Fugl-Meyer assessment (FMA) and Wolf motor function test (WMFT). The secondary outcomes included the performance in activities of daily living by the Barthel index (BI) and the quality of life by the 36-item short form health survey (SF-36).

The treatment compliance was similar in two groups (p=0.19). Both groups improved in motor performance, activities of daily living and quality of life. However, there were no significant differences in the FMA (p=0.58), WMFT (functional ability scale, p=0.33; performance time, p=0.44), BI (p=0.84) and SF-36 (physical, p=0.87; mental, p=0.99) scores between the groups.

The non-immersive VR system was feasible, effective and safe; however, it was not found to be superior to conventional physiotherapy. The trial was stopped early and did not reach its proposed sample size and hence, the findings are to be interpreted cautiously.

Clinical trial registry India: CTRI/2021/11/038339 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NTc1OTI=&Enc=&userName=CTRI/2021/11/038339).

Alcohol consumption is an increasingly recognised modifiable risk factor for dementia, yet whether it has differential impacts on dementia subtypes and its role in disease progression remains unclear. This study aims to: (1) quantify the association between alcohol intake and incidence of dementia subtypes and (2) examine whether individuals who drink heavily and develop dementia referred to hereafter as ‘alcohol-related’—have poorer post-diagnosis outcomes compared with other dementia cases. Clarifying these relationships will determine whether alcohol selectively increases risk for specific dementia phenotypes or broadly heightens neurodegenerative vulnerability, with implications for prevention, clinical counselling and therapeutic targeting.

This population-based cohort study of alcohol and dementia will use linked UK electronic health records from Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics (ONS). Participants will be eligible if they have available linked data from January 1998, when ONS death registrations became available, until the end of follow-up. Alcohol exposure will be defined through self-reported recorded weekly alcohol units and diagnostic codes for harmful or dependent alcohol use. Primary outcomes including incident all-cause and subtype-specific dementia (eg, Alzheimer’s, vascular, Lewy body, Parkinson’s, frontotemporal) as well as secondary outcomes (ie, mortality, care-home entry and neuropsychiatric symptoms). Key covariates encompassing socio-demographic factors, smoking and relevant comorbidities will be adjusted for. Multivariable Cox proportional hazards and Fine-Gray competing risk models will estimate associations with dementia incidence. Post-diagnosis prognosis will be compared for dementia in individuals with a history of heavy alcohol use (‘alcohol-related’) and dementia in individuals with minimal alcohol exposure (‘non-alcohol-related’) cases using survival and logistic regression models. Multiple testing correction will be applied across dementia subtype comparisons. Alcohol exposure will be modelled continuously and non-linearly using restricted cubic splines and categorically using binary indicators of harmful/dependent use. Missing covariate data will be assessed and addressed using appropriate methods, including multiple imputation and complete-case analysis. Data extraction and analysis are scheduled from October 2025 to October 2026.

Use of de-identified routine data will proceed under existing Research Ethics Committee and data governance approvals. Findings will be disseminated via open-access peer-reviewed journals, academic conferences and summaries targeted at patient, public and policy audiences. The results of this study will be reported according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) guidelines.

To explore experiences of healthcare providers, stroke survivors and caregivers on stroke transitional care delivery at a tertiary hospital in Tanzania.

A qualitative descriptive design with a phenomenological approach was used. Colaizzi’s thematic analysis was conducted using Dedoose software to identify significant information that describes the transitional care experiences of the study participants.

This study was conducted in the internal medicine and outpatient departments of a tertiary hospital in Tanzania.

15 triads of healthcare providers, stroke survivors and caregivers were purposively recruited to participate in semi-structured in-depth interviews between June and September 2024.

The analysis identified four themes: communication and exchange of information, involvement of patients and caregivers in transitional care, coordination of transitional care and experiences with changing care setting. Effective communication and information exchange among healthcare providers, survivors and caregivers ensured that survivors and their caregivers were well informed about the care process, clinical condition, prognosis and transitional care needs. A collaborative care approach enabled survivors and caregivers to actively participate in care, decision-making and discharge planning during hospital-to-home transition. Coordination of care was equally important during hospital-to-home transition as it provided survivors with home-care instructions and opportunities for follow-up care. However, miscommunication among the healthcare team, insufficient information exchange, inadequate discharge planning, poor social support and lack of care coordination prevented smooth hospital-to-home transition leading to a crisis at home.

The experiences of healthcare providers, patients and caregivers during stroke transitional care in Tanzania highlight achievements and key areas for improvement. Hospital-to-home transition is often characterised by uncertainty and emotional strain, emphasising the need for effective communication, involving patients and caregivers in care, as well as coordinating transitional care to address medical and psychosocial needs of survivors and their caregivers during and after discharge.

Dementia contributes to the disease burden worldwide, and people with hypertension or type 2 diabetes are at an elevated risk of developing dementia. It is essential to prevent or delay cognitive decline in people at high risk within the community. Our trials aim to evaluate the effects of adaptive cognitive training on community-dwelling older adults with hypertension or type 2 diabetes but no dementia.

Two multicentre, double-blind, randomised, placebo-controlled trials, named COgNitive Training in community-dwelling older adults at high risk for demENTia and with Hypertension (CONTENT-Hypertension) and COgNitive Training in community-dwelling older adults at high risk for demENTia and with Diabetes (CONTENT-Diabetes), will be conducted to investigate the effects of adaptive cognitive training on participants aged 60 years or above who have been diagnosed with hypertension or type 2 diabetes but no dementia. Each trial will enrol 120 participants. Participants will be recruited from the local community in Shijingshan and Haidian Districts, Beijing, and allocated to either the intervention or control group using a 1:1 ratio. The intervention group will engage in 12 weeks of adaptive cognitive training, while the control group will receive 12 weeks of placebo cognitive training. A 24-week follow-up assessment will be conducted for all participants to evaluate the persistence of the effects. The primary outcome is the 12-week change in Montreal Cognitive Assessment (MoCA) Basic scores from baseline to the end of the intervention (12 weeks). Secondary outcomes include 6-week and 24-week changes in the MoCA from baseline; 6-week, 12-week and 24-week changes in Trail Making Test-A&B (TMT-A, TMT-B), Digit Symbol Substitution Test, the WHO/University of California at Los Angeles Auditory Verbal Learning Test and Boston Naming Test scores of cognitive functions; 6-week and 12-week changes in Geriatric Depression Scale, Generalised Anxiety Disorder-7 (GAD-7), Pittsburgh Sleep Quality Index and 12-week change in blood pressure (CONTENT-Hypertension) or fasting blood glucose and glycated haemoglobin (CONTENT-Diabetes) from baseline.

This study will adhere to the ethical principles outlined in the Declaration of Helsinki and comply with international standards for Good Clinical Practice. All participants will sign the informed consent at baseline. This study has been approved by the Ethics Committee of Plastic Surgery Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (approval numbers: 2023-139 and 2024-162). The findings of the trials will be disseminated through publications in peer-reviewed scientific journals and presented at academic conferences.

NCT06512922 and NCT06524388.

Large-scale stroke registries can provide critical insights into disease mechanisms, progression and healthcare needs, informing prevention and care. However, few collect detailed demographic, brain imaging, and comprehensive long-term follow-up data. To address this, we established the prospective Stroke Investigation Group in North And central London (SIGNAL) registry in 2017.

The SIGNAL registry included 3931 adults aged ≥18 years with confirmed acute stroke (cerebral ischaemia or intracerebral haemorrhage (ICH)) admitted to the University College London Hospital hyperacute stroke unit between January 2017 and 2020, drawn from an ethnically diverse North and Central London population (~1.6 million). Baseline data included demographic, clinical, brain imaging and next-of-kin information. Six month follow-up included measures of functional status and non-motor outcomes (anxiety, depression, fatigue, sleep, pain, language, continence, social participation, cognition) via face-to-face, telephone or postal follow-up methods.

The mean age of individuals included in the SIGNAL registry was 72.1 years, and 1806 (45.9%) were female. The ethnic distribution comprised 2365 (60%) white, 649 (16.5%) black and 511 (13%) Asian. Stroke diagnoses included 3371 (85.8%) with cerebral ischaemia and 560 (14.2%) with ICH. On admission, 2240 individuals (57.0%) had a National Institutes of Health Stroke Scale score >4, indicating moderate stroke severity. At hospital discharge, the median functional outcome, measured by the modified Rankin Scale, was 3 (IQR 1–4), indicating moderate disability. At 6 months, functional outcomes measured with mRS were available for 3755 individuals (95.6%) with a median score of 1 (IQR=0–3) and non-motor outcomes were available for 3080 individuals (92.3%). The most prevalent adverse non-motor outcomes were fatigue 1756 (57%), reduced social participation 1694 (55%) and sleep disturbance 1663 (54%).

Further analyses of SIGNAL registry data will investigating associations between stroke mechanisms, subtypes and neuroimaging features and 6-month functional status, non-motor outcomes and cognitive impairment. Longer term follow-up of survivors for ~10 years is also planned.

Postherpetic neuralgia (PHN) is a debilitating complication of herpes zoster (HZ) that significantly impairs quality of life, disrupting sleep, daily activities and work capacity. Globally, PHN represents a major public health challenge, with marked heterogeneity in its epidemiological patterns across different regions and demographic groups. The escalating incidence of both HZ and PHN underscores the urgent need to elucidate modifiable and non-modifiable risk factors, which is critical for implementing targeted prevention strategies and optimising therapeutic interventions. Although previous studies have examined PHN risk factors, there remains a paucity of comprehensive, up-to-date systematic analyses evaluating its global epidemiological trends and associated determinants. This protocol presents the methodology of a planned systematic review to assess an updated global estimate of PHN epidemiology and synthesises critical risk factors associated with PHN prevalence or severity.

This systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We will search MEDLINE/PubMed, Embase, Web of Science, CENTRAL, PsycINFO, Google Scholar, CNKI, Wanfang and CBM for English/Chinese studies published from inception through April 2025. Eligible studies will include adults (≥18 years) with HZ or PHN that report PHN prevalence/incidence or relevant risk factors (eg, age, vaccination status, acute pain severity, comorbidities). Two reviewers will independently screen records, extract data (including study characteristics, demographics, risk factors and pain metrics) and assess risk of bias using Joanna Briggs Institute tools and ROBINS-I. Random-effects meta-analyses (R V.4.0) will pool PHN prevalence (logit-transformed Wilson scores) and ORs for risk factors, with subgroup analyses by geography, income level, clinical/demographic factors. Heterogeneity (I²≥50%) will trigger meta-regression or narrative synthesis. Sensitivity analyses will address bias robustness.

Ethics committee approval is not required. The results of the review will be published through an open access journal.

CRD42024510329.

The Chinese neuroimmunological disease database (NIDBase) cohort was established to explore genetic and environmental risk factors, clinical features, multi-omics data and prognostic biomarkers. The aim is to enhance our understanding of central nervous system (CNS) demyelinating diseases. Additionally, the establishment of this cohort will address the critical issue of the lack of comprehensive genetic data and biological samples for precision diagnosis and treatment research related to neuroimmunological diseases in China.

56 hospitals in various regions of China were selected to participate in this study. The patients diagnosed with CNS demyelinating diseases were recruited, including clinically isolated syndrome (CIS), multiple sclerosis (MS), neuromyelitis optica spectrum disease (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A).

At the time of patient enrolment, the clinical information is designated as baseline data. The collected baseline data include demographic information, disease history, clinical features of each demyelinating event, treatment records, standardised scales, questionnaire assessments and laboratory test results. Furthermore, biological samples, MRI and high-density electroencephalography (hd-EEG) data will be collected at baseline. All patients will be followed up at 3 months and 6 months and annually thereafter. As of December 2024, 3866 patients with CNS demyelinating diseases have been enrolled, including 84 CIS, 282 MOGAD, 1405 MS and 2095 NMOSD. Our findings indicate that CNS demyelinating diseases, particularly NMOSD, are more prevalent in women in China, with significant age differences observed among NMOSD patients compared with those with CIS, MS and MOGAD.

In future, all patients in our cohort will be followed up at 3 months and 6 months and then annually. By the end of December 2024, the database has been locked and is now being processed and analysed, while our data continue to be updated and expanded for further analysis. Both prospective and retrospective observations will be included in this study. Subsequent publications will emerge from this multicentre cohort, encompassing genomics, clinical cohort studies, hd-EEG biomarkers, imaging-based radiomics and electrical stimulation therapies.

NCT06443333.

By adopting the shared decision-making (SDM) model, this study aims to improve treatment adherence and patients’ subjective initiative. It intends to systematically explore the barriers and facilitating conditions for patients who had a stroke to participate in rehabilitation SDM through the analysis and integration of qualitative research methods. The ultimate goal is to provide a basis for optimising the formulation of rehabilitation plans, enhancing the quality of nursing services and improving patients’ medical experience.

The following databases were searched, with only literatures published in English or Chinese included: Cochrane Library, PubMed, Embase, Scopus, Web of Science, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedical Literature Database) and Wanfang Database. The search covered the period from the establishment of each database to 1 March 2025. The quality of the included literatures was evaluated using the Qualitative Research Quality Assessment Tool provided by the Joanna Briggs Institute in 2016, with a focus on factors affecting participation of patients who had a stroke in rehabilitation SDM.

A total of 1502 articles were retrieved in the preliminary search, and 10 were finally included. From these included literatures, 31 findings were extracted. Similar results were categorised and grouped into 10 new categories, which were further integrated into 3 core integrated findings: (1) patient-related factors, including interference from negative emotions, the gap between rehabilitation expectations and reality, the impact of socio-demographic factors and self-efficacy with stage-specific autonomous needs; (2) family-related factors, including family support, the impact of patients’ sense of responsibility to their families on decision choices and trade-offs forced by economic burden; (3) healthcare provider and environmental factors, including paternalistic models undermining autonomy, insufficient information and difficulty in screening hindering decision-making and discontinuity in the rehabilitation system and lack of resources increasing decision-making burden.

Through the meta-synthesis of qualitative studies, this research shows that negative emotions and realistic gaps reduce patients’ participation in decision-making. While family support helps enhance patients’ confidence in decision-making, economic burden affects their decision choices. Additionally, one-way doctor–patient communication, insufficient information support and discontinuity in the rehabilitation service system increase patients’ decision-making burden.

This study assessed whether a previously developed Monte Carlo simulation model can be reused for evaluating various strategies to minimise time-to-treatment in southwest Netherlands for endovascular thrombectomy (EVT) in patients who had an ischaemic stroke.

Reuse of a previously developed simulation model to simulate various strategies in another region, using prospectively collected data from stroke centres and retrospective data from emergency medical services.

Data from 509 patients who had an ischaemic stroke (≥18 years) treated with EVT (2014–2018) were used.

Input for the simulation model reuse included distributions of observed time delays along the acute stroke pathway. Validation of the baseline models was based on face validity and statistical measures (patient data vs model output) using the Assessment of the Validation Status of Health Economic decision models tool. We simulated strategies for a subregion: interhospital patient transfer by helicopter, transport of the neurointerventionalist to the primary stroke centre (‘drive-the-doctor’), interhospital patient transfer to a thrombectomy-capable stroke centre (TSC) outside the region and prehospital triage using the Rapid Arterial Occlusion Evaluation (RACE) scale.

Onset-to-groin time was the outcome.

Reuse of the original simulation model was obtained by minimal effort, implying limited adaptation. Compared with the baseline model, interhospital patient transfer by helicopter or to a TSC outside the region and prehospital routing using the RACE scale reduced mean onset-to-groin time by 16, 13 and 39 min, respectively (95% CrI for all: equal to the point estimate). ‘Drive the doctor’ reduced mean onset-to-groin time by 27 (car), 49 (ambulance) or 58 min (helicopter), each with a 95% CrI equal to the point estimate.

The original simulation model can be applied to different regions in the Netherlands. Strategies tested within the subregion resulted in promising results of ‘drive the doctor’ and prehospital patient routing using the RACE scale.

Parkinson’s disease (PD) is a common neurodegenerative disease, which has extensive pathology that critically includes the loss of midbrain dopaminergic neurons. This loss leads to debilitating motor features such as bradykinesia and rigidity, as well as some non-motor symptoms. Intracerebral dopamine cell transplants have been explored for many years as a new approach to treating PD and initially used human fetal ventral mesencephalic tissue with inconsistent results, related in part to major logistical challenges in sourcing enough tissue of the right quality and the limited possibilities for quality control and standardisation. Dopaminergic neurons can now be derived reliably from human stem cell sources, which may overcome some of the challenges associated with fetal tissue transplantations.

STEM-PD is a multi-centre, single-arm, dose-escalation, first-in-human advanced therapy investigational medicinal product (ATIMP) trial in Europe using a cell product that consists of dopaminergic neural progenitors derived from the RC17 human embryonic stem cell line. The aim of the study is to assess the safety, tolerability and feasibility of intraputamenal transplantation of this cell product in patients with moderately advanced PD. Eight participants will be recruited from two sites, Skånes University Hospital (Lund, Sweden) and Cambridge University Hospital (Cambridge, UK). The primary outcome of the trial is safety and tolerability, assessed by the number and nature of adverse events and serious adverse events, and the absence of space-occupying lesions on cranial MRI, in the first 12 months following transplantation. Secondary and exploratory outcomes, including clinical measures, changes in anti-Parkinson’s medication and measures of graft survival using positron emission tomography imaging, will be assessed at both 12 and 36 months post-grafting.

Ethical approval was obtained from the Swedish Ethical Review Authority (EPM dnr 2021-06945-01) and South Central - Oxford A Research Ethics Committee (reference 23/SC/0243). Clinical Trial Authorisation was given by the Swedish Medical Products Agency (Dnr: 5.1-2022-57953) and the Medicines and Healthcare products Regulatory Agency for clinical trials authorisation (reference CTA 40773/0001/001-0001). Authorisation for transfer to Clinical Trial Regulation (EU) 536/2014 was given by the Swedish Medical Products Agency (Dnr: 5.1.1-2024-100773). Potential participants will receive verbal and written information about the trial and written informed consent will be obtained prior to enrolment. A lay summary of the results of the trial will be uploaded to the trial website which is publicly accessible. Trial results will be published in peer-reviewed journals.

NCT05635409.

Parkinson’s disease (PD) is a neurodegenerative disorder characterised by heterogeneous motor symptoms, non-motor symptoms and rates of disease progression; phenotype and prognosis vary by individual. Although researchers have attempted to predict clinical outcomes using biomarkers and other variables, there are limited data on the development, validation and clinical utility of multivariable prediction models for individual prognostication in PD. In this protocol, we will develop a method for identifying, reviewing and appraising existing PD prognostic models in order to summarise the current literature, identify knowledge gaps and inform future research.

This scoping review will be guided by the methodological principles outlined in the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews. We will include all multivariable models that predict disease progression in individuals with PD using traditional statistical methods or machine learning. We will exclude models that only report performance measures for one variable (ie, univariable models) or only provide effect estimates (eg, OR, HR). A detailed search of peer-reviewed research publications will be performed through 2025 using the following electronic databases: PubMed, EMBASE, Web of Science and Scopus. Article data will be extracted using Covidence. Two independent reviewers will screen articles by title and abstract for relevance, and a third reviewer will resolve any discrepancies. The remaining full-text articles will also be screened by two independent reviewers, and a third reviewer will resolve any discrepancies. Results from multivariable prediction models meeting inclusion criteria will be summarised using narrative synthesis and organised by clinical outcome. Models will also be appraised using Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis + Artificial Intelligence (TRIPOD+AI) and Prediction model Risk Of Bias ASsessment Tool (PROBAST) guidelines to identify deficiencies and areas of future study.

Ethical approval is not required for this scoping review. Findings will help clinicians make evidence-based decisions to improve prognostication in PD. Findings can also be used to inform the development and validation of additional multivariable clinical prediction models in PD. The results of this scoping review will be disseminated through peer-reviewed publications, research reports and presentations at relevant conferences.

For people whose stroke risk would be reduced by taking a long-term oral anticoagulant (OAC), it is important to implement effective strategies to support medication initiation, adherence and persistence. To do this, a better understanding of the factors associated with implementation of interventions to optimise OAC management is needed.

This scoping review aimed to summarise the evidence-based characteristics associated with implementing interventions designed to optimise long-term OAC adherence.

Primary research (published post-2000) evaluating any intervention designed to optimise implementation of long-term OAC for stroke prevention by way of change in OAC services, staff or patient behaviour.

Five databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Cochrane Library) were searched from 1 January 2000 to 4 August 2023 using a combination of terms relating to population, intervention and study design.

Titles/abstracts were screened by at least one reviewer. Data from each full text were abstracted (with 20% double-checked for accuracy) and its implementation content reviewed, guided by the Expert Recommendations for Implementing Change strategies.

216 studies were included, with varying descriptive reporting of implementation strategies, and only 61 (28%) self-identifying as an implementation study. The median number of implementation strategies used was three, with recently published studies (2015 onwards), those including patients receiving either direct OACs (DOACs) or vitamin K antagonists (VKAs) and those including multiple intervention targets (service, staff or patients) associated with using more implementation strategies. ‘Train and educate stakeholders’ strategies were the most commonly used, and ‘Adapt and tailor to the context’ strategies were the least used by included studies. Conversely, self-defined implementation studies were less likely to use ‘Train and educate stakeholders’ strategies, although they were positively associated with use of ‘Adapt and tailor to the context’. ‘Use evaluative & iterative’ strategies were used more frequently in studies where patients used either VKAs or DOACs, or were published more recently.

Studies need to self-define as implementation studies, improve implementation strategy reporting and be transparently registered, alongside conducting process evaluations or more richly describing implementation processes. Future research could explore why some implementation strategies are used more than others and whether aligning strategy clusters with intervention targets results in clinically significant differences in patient care.

Spinal cord injury (SCI) results in debilitating sensory, functional deficits and paralysis requiring neurorehabilitation solutions. In this regard, focal muscle vibration (FMV) is an emerging neuro-rehabilitation tool that uses mechanical vibration on muscles/tendons to stimulate underlying nerves and consequently modulate neural pathways. We conducted a systematic review to understand the exact effectiveness of FMVs on the sensorimotor function and mobility/strength in the SCI population.

Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach.

PEDro, Springer, PubMed, Science Direct, Cochrane Library and Google Scholar were searched through 15 February 2025.

We included studies adhering to the following population–intervention–comparison–outcomes (PICO) elements. Population: SCI, intervention: FMV, comparison: unexposed controls, outcome: either of sensorimotor function or mobility and strength.

Two independent reviewers used standardised methods to search, screen and code included studies. Risk of bias was assessed using the Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) scale. Findings were summarised and a narrative synthesis is provided.

25 studies were included. 9 studies used FMV in the upper limb and 14 in the lower limb. The analysis includes 427 patients with SCI, with a focus on male, chronic SCI cases and a prevalence of North American studies.

Our systematic review of 25 studies, with 21 (84%) reporting positive outcomes, suggests that FMV may improve sensory perception, motor function, mobility and strength in individuals with SCIs, with benefits observed in both limbs. However, substantial heterogeneity in FMV parameters, study designs, participant characteristics and the high prevalence of serious/critical risk of bias (13/25 studies, 52%) limit definitive conclusions. Further research with optimised protocols, larger sample sizes and longitudinal designs is needed to confirm efficacy and establish clinical guidelines.

Atrial fibrillation (AF) is the leading cause of cardioembolic stroke and is associated with increased stroke severity and fatality. Early identification of AF is essential for adequate secondary prevention but remains challenging due to its often asymptomatic or paroxysmal occurrence. Artificial intelligence (AI) offers new possibilities by integrating biomarkers, clinical phenotypes, established risk factors and imaging features to define a personalised ‘digital twin’ model. The TAILOR study aims to (1) examine prospective detection of AF using monitoring devices, (2) investigate novel prognostic MRI markers in patients with an AF-related stroke (AFRS) and (3) validate AI-based models for outcome prediction in AFRS.

This prospective multicentre observational cohort study includes patients aged 40 years and above, with neuroimaging-confirmed diagnosis of ischaemic stroke, recruited from two sites: Hospital del Mar Barcelona (Spain) and Radboud University Medical Centre (The Netherlands). For the first sub-study (n=300), patients will undergo clinical assessment at baseline, 3 months and 12 months, and patch-based or Holter cardiac monitoring. The second sub-study (n=200) involves repeated brain MRI and cognitive examination after AFRS. Finally, AI-driven ‘digital twin’ models developed on retrospective TARGET datasets will be prospectively evaluated in TAILOR using temporal and centre-stratified analyses for advanced predictive tools for AF and AFRS outcomes.

The TAILOR study was approved by local ethics boards in Barcelona (CPMP/ICH/135/95) and Medical Research Ethics Committee Oost-Nederland (NL86346.091.24). Patients will be included after providing informed consent. Study results will be presented in peer-reviewed journals and at global conferences.

Accumulating evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists may have therapeutic effects against Parkinson’s disease (PD); however, clinical evidence has not yet been established and remains controversial. This clinical study aims to assess the efficacy, disease-modifying effects, safety and optimal dose of oral semaglutide tablets, a GLP-1 receptor agonist, in idiopathic patients with PD.

The MOST-ABLE study is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial of oral semaglutide tablets in 99 participants with PD. Patients with PD (Hoehn & Yahr stages 1–2.5) at eight sites in Japan will be randomly assigned in a 1:1:1 ratio to one of three groups: oral semaglutide tablets (7 mg or 14 mg) or placebo. The study drugs will be administered once daily as an add-on to conventional medical treatment for PD. After 36 weeks of treatment, the participants will be treated without the study drugs for 12 weeks. The efficacy outcomes include Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Parkinson’s Disease Questionnaire-39, cognitive tests and dopamine transporter imaging. The primary endpoint is the change in the MDS-UPDRS part 3 score in the practically defined off-medication state from baseline at 48 weeks between the treatment allocation groups. The safety and tolerability will also be evaluated.

The study protocol was approved by the Pharmaceuticals and Medical Devices Agency of Japan and the study was approved by the institutional review boards at the University of Osaka Hospital and each study site. All participants are required to provide informed consent. The results will be disseminated in peer-reviewed journals, presented at scientific meetings and presented to patients in a lay summary format.

jRCT2051230090 (https://jrct.mhlw.go.jp/latest-detail/jRCT2051230090), universal trial number U1111-1271-3794.

Long-term brain health profiles following exposure to repetitive head impacts and/or concussions in contact sports are a public health focus and the subject of a national debate. The true prevalence rates of mild cognitive impairment (MCI) or neurobehavioural dysregulation are unknown in the nearly 20 000 current/living former professional football players. Here, we describe the procedures and methodology of the prevalence study of cognitive function in former professional football players from the Brain Health Initiative at the University of Pittsburgh. The objective is to define the prevalence of normal cognitive function versus neurodegeneration in former professional football players through clinical, neuroimaging and biomarker assessments.

Participants include former professional football players aged 29–59 years at study onset who played a minimum of three professional football games in three professional seasons and non-exposed controls. Participants are recruited by two mechanisms, a random and non-random sample. The full study protocol includes a 3–4-day, multidomain assessment (eg, neurological, neurocognitive, psychiatric, sleep, vestibular, orthopaedic and cardiovascular) for neurodegenerative disease and overall health and function, including MRI, positron emission tomography scans, analysis of blood plasma and cerebrospinal fluid, neurocognitive assessments, applanation tonometry, overnight sleep study and informant interview. A multidisciplinary clinical panel conducts a blinded diagnostic consensus conference to adjudicate the presence of MCI and/or traumatic encephalopathy syndrome, which serve as the study’s primary and secondary outcomes, respectively. Point prevalence of these for both the exposed and unexposed cohorts will be calculated as the primary statistical analysis.

The University of Pittsburgh Institutional Review Board approved the study prior to recruiting human subjects (protocol numbers STUDY19010008: sIRB - Brain Health Initiative (Part 1) and STUDY19030211: sIRB - Brain Health Initiative (Part 2)). The results will be disseminated in peer-reviewed journals and as presentations at national and international scientific conferences.

This article outlines the research protocol for a multicentre, randomised, controlled study designed to evaluate the therapeutic effect of a modified olfactory training (MOT) based on bi-directional nasal drug delivery system for patients with postinfectious olfactory dysfunction (PIOD), and to compare its efficacy with conventional olfactory training (COT).

This is a multicentre study in which patients will be recruited from several participating hospitals. Patients will be divided into three groups: COT group using COT device, MOT group using MOT device, Control group without any intervention other than follow-up. The olfactory training (OT) intervention will last for 12 months. The primary outcome will be the improvement in olfactory ability from baseline measurement to the end of intervention or control period, evaluated through the total Threshold, Discrimination, Identification (TDI) score of the Sniffin’ Stick test. Secondary outcomes will be changes in olfactory bulb volume and shape, olfactory-related brain area volume, olfactory and trigeminal nerve-related potentials, and subjective assessments.

This study protocol has been registered with ClinicalTrials.gov. The Peking University Third Hospital Medical Science Research Ethics Committee reviewed and approved this study protocol. The results will be published in BMJ Open.

NCT06829706.

Frontotemporal dementia (FTD) remains challenging to diagnose owing to the marked clinical heterogeneity associated with the disease. This heterogeneity stems from the complex interplay of various clinical phenotypes, genetic mutations and underlying neuropathologies, such as TDP-43 and tau proteinopathies. Currently, there is no single confirmed biomarker that can reliably diagnose disease, specifically disease stage, disease subtype and underlying neuropathology. Recent research has indicated that neuroimaging techniques hold the most promise for the discovery of FTD biomarkers. We propose a protocol for a systematic review and meta-analysis to identify MRI and fluorodeoxyglucose positron emission tomography (FDG-PET) biomarkers associated with clinical, genetic and pathological subtypes of FTD. We aim to address the following research questions: can regional MRI volumetry and FDG-PET hypometabolism differentiate (1) FTD patients from healthy controls; (2) sporadic cases of FTD from healthy controls; (3) genetic cases of FTD (MAPT, GRN, and C9orf72 mutations); and (4) underlying neuropathology, specifically discriminating between tau- and TDP-43-based FTD?

Literature searches will be performed across three databases: Ovid Medline, Ovid Embase and Web of Science. Publications that have fewer than five participants, are non-human-based, not written in the English language or contain unpublished data will be excluded. Two independent investigators will screen and subsequently evaluate which publications to include. Should any disagreements arise, a third investigator will settle the discrepancy. After the random-effects meta-analysis has been used to extract and pool the data, I² analysis will be used to quantify heterogeneity.

Ethics approval will not be required for this research. On completion, the systematic review and meta-analysis will be published in a peer-reviewed journal.

CRD42024545302.