Background Stroke disproportionately affects individuals with lower socioeconomic status (SES). This study investigates socioeconomic inequalities in stroke care and long‐term outcomes since 1995. Methods Using the South London Stroke Register (1995–2024), SES was measured at the area‐level (Index of Multiple Deprivation [IMD]) and individual‐level (occupation). Associations between SES and stroke unit admission, thrombolysis, and poststroke disability (Barthel Index/0–14), dependency (Frenchay Activities Index/0–15), and depression (Hospital Anxiety and Depression Scale/8–21) were estimated using multivariable logistic regression; and SES‐effect on 5‐year survival was estimated using Kaplan‐Meier and Cox Proportional‐hazard models. Results A total of 7714 participants were included (median age [interquartile range]: 70.9 years [59.0–80.8 years]; women: N=3677 [47.7%]). SES was not associated with stroke unit admission (IMD 1 (most deprived) versus IMD 3/4/5 (least deprived): odds ratio 0.90 [95% CI 0.76–1.08]; routine/manual versus nonroutine/nonmanual occupation: 1.04 [0.92–1.17]) or thrombolysis (0.91 [0.66–1.25]; 0.94 [0.75–1.16], respectively). Poorer survival of participants with lower SES in 1995 to 2003 (IMD 1 versus IMD 3/4/5: hazard ratio 2.24 [95% CI 1.81–2.76]; routine/manual versus nonroutine/nonmanual: 1.09 [0.98–1.24]) was not observed in 2013 to 2022 (1.02 [0.82–1.26]; 0.97 [0.82–1.15]). A total of 3944 completed 3‐month (64.8% of alive) and 2364 5‐year follow‐ups (69.4%). In stroke‐year/age/sex‐adjusted analyses, participants with lower SES persistently experienced higher rates of 3‐month and 5‐year disability and dependency and 5‐year depression. Further adjustments for ethnicity, vascular risk factors, stroke type/severity and acute interventions had minor attenuating effects. Conclusions Access to key acute interventions was equitable and the survival disadvantage of participants with lower SES declined. Persistent inequalities in functional and mental health outcomes might be driven by factors beyond acute interventions (eg, rehabilitation access or post‐acute social support), requiring integrated care approaches addressing clinical and social determinants of stroke recovery.

Abstract Background and aims We aim to evaluate the impact of statin prescription on stroke risk in patients with hypercholesterolaemia and to assess disparities in statin prescribing. Methods We analysed electronic health records from patients with hypercholesterolaemia, registered in 41 general practices in south London between 2005 and 2021. The causespecific hazard ratio of statin prescription on stroke, adjusted for patients’ sociodemographic characteristics and stroke risk factors (smoking ever, hypertension, and diabetes), was estimated using a time-varying exposure Cox proportional hazards model stratified by history of heart diseases. The association between statin prescription and patients’ sociodemographic characteristics was evaluated using a logistic regression. Results Of the 849,968 registered patients, 166,124 (19.5%) had records of hypercholesterolaemia. Among them, 33.5% were prescribed statins, 2.6% had a record of stroke, and 50.6% were female, 31.7%, 16.2% and 8.9% had records of hypertension, diabetes and history of heart diseases respectively. In a Cox model stratified by history of heart diseases, statin prescription was associated with a reduced hazard of stroke (cause-specific hazard ratio: 0.74; 95% confidence interval (CI): 0.68–0.80, p<0.001), with follow-up administratively censored at 79 years (n=161,527; 97.2%). Statins were less likely prescribed to female patients and patients of Black ethnicity (odds-ratio: 0.70, 95% CI: 0.68-0.72, p<0.001 and odds-ratio: 0.82, 95% CI: 0.79-0.85, p<0.001, respectively, see attached figure). Conclusions Statin therapy prescription is associated with reduced stroke risk in patients with hypercholesterolaemia, yet it was under-prescribed to women and patients of Black ethnicity, highlighting avoidable disparities in preventive care. Conflict of interest Marc Delord and Abdel Douiri: nothing to disclose Table 1 - belongs to Results

Importance:Hospital-based ophthalmology faces increasing demand for long-term monitoring of neovascular age-related macular degeneration (nAMD). Safe redistribution of routine monitoring to community clinicians is relevant to integrated community (primary)-secondary care models. Objective:To examine whether community optometrist-led monitoring of nAMD is noninferior to hospital-based monitoring for detecting disease activity requiring treatment. Design, Setting, and Participants:This multicenter, noninferiority randomized clinical trial was conducted from October 8, 2019, to January 31, 2024, at secondary centers (17 hospitals) and primary centers (60 community optometry practices) with 12-month follow-up. Statisticians were masked to patient grouping. Adults 55 years or older with quiescent AMD in at least 1 eye (and quiescent or nonneovascular disease in the other) were recruited at participating hospitals. Data analysis was performed from October 2024 to March 2025. Interventions:Participants were randomized 1:1 to monitoring sessions once every 2 months in hospitals (control) or community practices (intervention). Trained and accredited optometrists performed optical coherence tomography imaging, clinical examination, patient management, and online reporting at each visit. Main Outcomes and Measures:The primary outcome (participant level) was a binary indicator of whether a false-negative clinical management decision occurred at any visit within 12 months (missed quiescent nAMD reactivation or new fellow-eye nAMD, adjudicated by a central reading-center reference standard). The noninferiority margin was a 10-percentage point absolute risk difference. Secondary outcomes were false-positive clinical management decisions, attendance adherence, visual acuity change, harms, loss to follow-up, suspicious classifications, and confirmation visit outcomes. Results:Of 704 randomized participants, 635 (90.2%) completed at least 1 follow-up visit, including 287 at community practices (mean [SD] age, 80.6 [8.1] years; 236 [67.4%] female) and 348 at hospitals (mean [SD] age, 80.1 [8.5] years; 203 [57.3%] female). False-negative clinical management decisions occurred in 11 of 287 community participants (3.8%) vs 27 of 348 hospital participants (7.8%) (risk difference, -3.9 percentage points; 95% CI, -7.4 to -0.3 percentage points; P = .04; adjusted odds ratio, 0.51; 95% CI, 0.24-1.07; P = .08), meeting noninferiority. False-positive clinical management decisions occurred in 24 of 287 community participants (8.4%) vs 12 of 348 hospital participants (3.5%) (risk difference, 4.9 percentage points; 95% CI, 0.9-9.0 percentage points). Findings were consistent across per-protocol, cluster-adjusted, and relative risk sensitivity analyses. No adverse event-related withdrawals occurred. Conclusions and Relevance:In this randomized clinical trial, community optometrist-led monitoring of quiescent nAMD was noninferior to hospital monitoring for detecting disease activity requiring treatment. These results provide evidence for its use in integrated clinical care models. Trial Registration:ClinicalTrials.gov Identifier: NCT03893474.

Decentralised clinical trials (DCTs) can gather objective data in real-world settings through digital health technologies (DHTs) to obtain real-time measurements of clinical outcomes. However, such measurements remain infrequent in clinical trials of investigational medicinal products (CTIMPs). We review the decentralisation of CTIMPs, identify barriers to passive, real-time DHT use and recommend four solutions: a swift regulatory approval process for DHTs in clinical trials; development of specialised DHTs for CTIMPs; integration of human factors into DHT design for CTIMPs; and the adoption of data collection and transmission standards to enable decentralised CTIMPs to function effectively in patient homes.

INTRODUCTION:Policy shifts towards home-based care are reshaping the management of stroke survivors, many of whom require long-term support. Home care, which encompasses social care for personal and household tasks and informal care provided by family and friends, plays a crucial role in post-stroke recovery and community reintegration. This study examined home care use up to 15 years post-stroke and its associated factors, and assessed unmet needs for assistance with activities of daily living (ADLs). PATIENTS AND METHODS:Data from 7885 stroke survivors in the South London Stroke Register (1995-2022) were analysed at 3 months, 1, 5 and 15 years post-stroke. Descriptive analyses examined home care patterns and unmet needs. A Heckman selection model assessed factors associated with home care use while accounting for missing data. RESULTS:On average, 75% of stroke survivors used home care across 15 years post-stroke, with 83% of care at 3 months and 87% at 15 years being provided through informal care. Home care use was more likely among those with functional dependency (29%; 95% CI, 22%-35%) and those living with family (24%; 95% CI, 21%-27%). Social care use was higher in people with greater dependency (48%; 95% CI, 42%-56%), those living alone (25%; 95% CI, 21%-29%), those with lower deprivation (10%; 95% CI, 1%-20%) or those with a Black ethnic background (6%; 95% CI, 2%-9%). Informal care use was higher among those living with family (12%; 95% CI, 9%-14%), those with moderate dependency (2%; 95% CI, 0.1%-5%) or females (6%; 95% CI, 3%-9%). Unmet needs in ADLs increased over time (12% at 3 months to 17% at 15 years) and were higher among those with moderate compared with severe functional dependency. DISCUSSION AND CONCLUSIONS:Within home care, informal care remains the predominant long-term support for stroke survivors, persisting up to 15 years after stroke. Addressing health-related, socio-economic, ethnic and gender disparities in home care and unmet needs is essential for equitable community-based stroke care, and caution is needed when promoting home-based care models regarding the distributional impact of home care. Accurate measurement of home care is key to improving post-stroke care models and quality of life.

OBJECTIVES:Limited data exist on the impact of secondary stroke prevention and on cognitive function after stroke. This study aims to investigate whether post-stroke care strategies protect cognitive function up to ten-year. MATERIALS AND METHODS:Data were collected between 1995 and 2018 from the population-based South London Stroke Register (SLSR, n = 6504). Multivariable Poisson regression models with robust standard errors and confounders were constructed to evaluate adjusted relative risks (aRRs) between cognitive impairment and different treatment strategies; before, at acute care or after stroke. Use multiple imputation to manage the missing data. RESULTS:The prevalence of cognitive impairment was 29% (confidence interval (CI) 26-32). 5-years after stroke, in ischemic stroke patients with a history of atrial fibrillation (AF), there was a reduced risk of cognitive impairment of 50% associated with antihypertensive (aRR:0.5, 0.27-0.91), 77% with statin (aRR:0.23, 0.06-0.91) and 82% with anticoagulant (aRR:0.18, CI 0.05-0.64). In ischemic stroke patients with no history of AF, the reduced risk was 26% (aRR:0.74, 0.57-0.95) with antihypertensive and 19% (aRR:0.81, 0.64-1.03) with statin. All these protective associations tend to diminish over time up to ten years after stroke. When clinically indicated, a combined treatment of these were strongly associated with a reduced risk of cognitive impairment. Small risk reduction was observed between cognitive impairment and acute stroke unit admission (aRR:0.96, 0.93-0.98). CONCLUSIONS:Consistent use of combined treatments is associated with better cognitive function up to 10 years post-stroke. These findings suggest that optimizing medication management could help reduce the risk of long-term cognitive decline.

The ICD-11 stroke definition expands stroke diagnosis by including neuroimaging-confirmed brain lesions regardless of symptom duration. Using directly age- and sex-standardized rates from the South London Stroke Register applied to UK Census 2021/2022 populations, we projected that ICD-11 to increase UK stroke incidence by ∼4.2%, yielding an estimated 2771 additional cases annually (England +2313; Scotland +241; Wales +142; Northern Ireland +75). Ethnicity-adjusted estimates suggested a 6.2% increase for England and Wales. These projections are scenario estimates that assume South London rates apply uniformly across the UK, their central limitation, and their realization will depend on local imaging and referral practice. Many additional cases will likely be managed in outpatient settings, requiring expanded provision, improved MRI, and strengthened cardiovascular prevention.

Abstract Background and aims Specialist community-based Stroke Rehabilitation (SSR), delivered through Early Supported Discharge (ESD) and Community Stroke Rehabilitation (CSR), is increasingly provided within the Integrated Community Stroke Service model. This study aims to describe trends and case-mix and to evaluate the long-term impact of SSR on survival and other post-stroke outcomes. Methods Linked data of the South London Stroke Register to the Sentinel Stroke National Audit Programme between 2013 and 2024 is used. SSR was defined as receipt of specialist ESD, CSR, or combined ESD–CSR services. Descriptive methods were used to compare case-mix. Survival up to five years post-stroke was examined using Kaplan–Meier curves and Cox proportional hazards models. Outcomes included functional independence, Instrumental activities of daily living, cognitive impairment, depression and anxiety, and quality of life. Long-term outcomes were evaluated using doubly robust estimation with propensity score matching. Results Among 1,910 stroke survivors, 64% received SSR. SSR increased over time and was common among those with moderate functional disability at discharge (P < 0.00), Black ethnic groups (P < 0.00), and those living in private houses (P < 0.00). SSR associated with shorter inpatient stays and higher five-year survival (Log-rank test, P < 0.0034) or reduced risk of death (hazard ratio 0.62; 95% CI 0.51–0.76). SSR improved functional dependency at 3 months and 1 year post-stroke, with Barthel Index scores increasing by 2.7 and 2.1 points, respectively (P < 0.001), but no significant effects on other long-term outcomes. Conclusions SSR is associated with improved survival and functional outcomes following stroke, supporting continued investment in integrated community stroke rehabilitation services. Conflict of interest All authors: Nothing to disclose.

Ethnic inequalities in stroke incidence are well-established, but long-term trends and the impact of socioeconomic status (SES) remain understudied. We estimated incidence rates by ethnicity over 30-years, and differences by SES, using the South London Stroke Register (1995–2024). We conducted a population-based study including all residents of a geographically defined area of South London, calculating standardised incidence rates using census-derived denominators and the 2013 European Standard Population. The area-level Index of Multiple Deprivation was the indicator of SES. Poisson regression estimated incidence rate ratios comparing ethnic-minority vs White groups, adjusting for age, sex, and SES, with ethnicity-SES interaction testing and marginal rates derived by subgroup. Among 7,726 people with first-ever stroke, overall standardised incidence decreased 34% between 1995–1999 and 2010–2014 (198;[187.8–208] to 131;[122.4–138.9] per 100,000), then increased 13% in 2020–2024. Black-African and Black-Caribbean populations had higher baseline incidence persisting across all periods. Ethnic inequalities narrowed initially but subsequently widened, with incidence twice as high in Black-African (IRR=2.31;[2.03–2.62]) and Black-Caribbean (IRR=2.00;[1.73–2.31]) groups compared to White groups in 2020–2024. Patterns were consistent across stroke subtypes, with the largest inequalities in primary intracerebral haemorrhage. Ethnic differences in incidence attenuated on SES adjustment but remained significant. Within ethnic groups, most deprived Black-African and Black-Caribbean populations showed highest incidence. Stroke incidence has risen sharply in the past five years, driven by rising incidence rates in Black-African and Black-Caribbean populations, with reduction in the White population. Achieving equity requires ensuring uptake of cardiovascular risk programmes across all socioeconomic and ethnic groups, with earlier risk management for groups who develop stroke 10-12 years younger than the general population.

Abstract Background We aim to evaluate the impact of statin prescription on stroke risk in patients with hypercholesterolaemia and to assess disparities in statin prescribing. Methods We analysed electronic health records from patients with hypercholesterolaemia, registered in 41 general practices in south London between 2005 and 2021. The cause-specific hazard ratio of statin prescription on stroke, adjusted for patients’ sociodemographic characteristics and stroke risk factors (smoking ever, hypertension, and diabetes), was estimated using a time-varying exposure Cox proportional hazards model stratified by history of heart diseases. The association between statin prescription and patients’ sociodemographic characteristics was evaluated using a logistic regression. Results Of the 849,968 registered patients, 166,124 (19.5%) had records of hypercholesterolaemia. Among them, 33.5% were prescribed statins, 2.6% had a record of stroke, and 50.6% were female, 31.7%, 16.2% and 8.9% had records of hypertension, diabetes and history of heart diseases, respectively. In a Cox model stratified by history of heart diseases, statin prescription was associated with a reduced hazard of stroke (cause-specific hazard ratio: 0.74; 95% confidence interval (CI): 0.68–0.80, p < 0.001), with follow-up administratively censored at 79 years (n = 161,527; 97.2%). Statins were less likely prescribed to female patients and patients of Black ethnicity (odds ratio: 0.70, 95% CI: 0.68–0.72, p < 0.001 and odds ratio: 0.82, 95% CI: 0.79–0.85, p < 0.001, respectively). Conclusions Statin therapy prescription is associated with reduced stroke risk in patients with hypercholesterolaemia, yet it was under-prescribed to women and patients of Black ethnicity, highlighting avoidable disparities in preventive care.

BACKGROUND:Elective left ventricular (LV) unloading during high-risk percutaneous coronary intervention (PCI) is hypothesized to mitigate hemodynamic instability and myocardial stunning, but has not been evaluated in a randomized trial. OBJECTIVES:This prespecified substudy of the CHIP-BCIS3 (Controlled Trial of High-risk Coronary Intervention With Percutaneous Left Ventricular Unloading) trial evaluated whether elective LV unloading with a microaxial flow pump (mAFP) reduces hemodynamic instability and postprocedural stunning. METHODS:Patients with severe LV systolic dysfunction undergoing complex PCI were randomized to elective LV unloading with an mAFP or standard care. Invasive hemodynamics were assessed using pulmonary artery catheterization at baseline and post-PCI. The coprimary outcomes were systolic blood pressure reduction, loss of pulse pressure (LOPP), and requirement for inotropes. Secondary outcomes included changes in cardiac index, LV filling pressure, and frequency of peri-procedural myocardial injury. RESULTS:Of 125 eligible patients, 97 were enrolled (50 mAFP; 47 standard care). Baseline cardiac index was 2.10 ± 0.55 L/min/m2. The incidence of systolic blood pressure reduction was similar between groups (relative risk [RR]: 0.86; 95% CI: 0.58-1.29), whereas inotrope use was lower with mAFP (RR: 0.57; 95% CI: 0.34-0.97). LOPP was more frequent with mAFP (RR: 7.83; 95% CI: 2.53-24.24) and was associated with peri-procedural myocardial injury (OR: 3.00; 95% CI: 1.00-9.03). Changes in cardiac index (-0.25 vs -0.24 L/min/m2; P = 0.20) and pulmonary capillary wedge pressure (2 vs 3 mm Hg; P = 0.79) were similar between groups. CONCLUSIONS:In patients undergoing complex PCI, elective LV unloading with mAFP reduced inotrope requirements but increased LOPP and did not prevent myocardial stunning. (Controlled Trial of High-risk Coronary Intervention With Percutaneous Left Ventricular Unloading [CHIP-BCIS3]; NCT05003817).

Background:COPD is a major global health burden, associated with high rates of mortality, readmissions and cardiovascular disease (CVD) complications. Predictive models, including statistical and machine learning (ML) approaches, have been developed to support risk stratification and clinical decision-making. This review assesses their performance and generalisability. Methods:A systematic search of EMBASE, MEDLINE and PubMed identified studies published since 2015 evaluating predictive models for COPD-related outcomes. Studies were screened using predefined criteria, and model performance was synthesised via meta-analysis. Pooled area under the curve (AUC) values were calculated for each model type. Risk of bias was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). Results:Of 3 488 records screened, 37 studies met inclusion criteria: 20 focused on mortality, 14 on readmissions and six on CVD complications. Statistical models had a pooled AUC of 0.787 (95% CI 0.755-0.816). For mortality, statistical models outperformed or matched ML models (AUC 0.801 versus 0.760; p=0.1195), while ML models outperformed statistical approaches for readmissions (AUC 0.812 versus 0.758; p=0.4423). CVD outcomes showed a pooled AUC of 0.810 (95% CI 0.749-0.859). External validation often reduced ML model performance, raising concerns about overfitting. Conclusions:ML models improve readmission prediction but offer no consistent advantage for mortality, where statistical models perform similarly. ML models face generalisability challenges due to overfitting. Future work should emphasise real-world validation and hybrid approaches to enhance interpretability and clinical applicability in COPD care.

QuestionIs community optometrist-led monitoring of quiescent neovascular age-related macular degeneration noninferior to hospital monitoring for identifying disease activity requiring treatment?FindingsIn this randomized clinical trial of 635 adults, false-negative clinical management decisions occurred in 3.8% in the community group and 7.8% in the hospital group for a difference of -3.9 percentage points, meeting the criterion for noninferiority.MeaningThis study's results support the use of community optometrist-led monitoring of quiescent neovascular age-related macular degeneration for detecting disease activity requiring treatment in integrated clinical care models. This randomized clinical trial examines whether community-based monitoring of neovascular age-related macular degeneration is noninferior to hospital monitoring for identifying disease activity requiring treatment. ImportanceHospital-based ophthalmology faces increasing demand for long-term monitoring of neovascular age-related macular degeneration (nAMD). Safe redistribution of routine monitoring to community clinicians is relevant to integrated community (primary)-secondary care models.ObjectiveTo examine whether community optometrist-led monitoring of nAMD is noninferior to hospital-based monitoring for detecting disease activity requiring treatment.Design, Setting, and ParticipantsThis multicenter, noninferiority randomized clinical trial was conducted from October 8, 2019, to January 31, 2024, at secondary centers (17 hospitals) and primary centers (60 community optometry practices) with 12-month follow-up. Statisticians were masked to patient grouping. Adults 55 years or older with quiescent AMD in at least 1 eye (and quiescent or nonneovascular disease in the other) were recruited at participating hospitals. Data analysis was performed from October 2024 to March 2025.InterventionsParticipants were randomized 1:1 to monitoring sessions once every 2 months in hospitals (control) or community practices (intervention). Trained and accredited optometrists performed optical coherence tomography imaging, clinical examination, patient management, and online reporting at each visit.Main Outcomes and MeasuresThe primary outcome (participant level) was a binary indicator of whether a false-negative clinical management decision occurred at any visit within 12 months (missed quiescent nAMD reactivation or new fellow-eye nAMD, adjudicated by a central reading-center reference standard). The noninferiority margin was a 10-percentage point absolute risk difference. Secondary outcomes were false-positive clinical management decisions, attendance adherence, visual acuity change, harms, loss to follow-up, suspicious classifications, and confirmation visit outcomes.ResultsOf 704 randomized participants, 635 (90.2%) completed at least 1 follow-up visit, including 287 at community practices (mean [SD] age, 80.6 [8.1] years; 236 [67.4%] female) and 348 at hospitals (mean [SD] age, 80.1 [8.5] years; 203 [57.3%] female). False-negative clinical management decisions occurred in 11 of 287 community participants (3.8%) vs 27 of 348 hospital participants (7.8%) (risk difference, -3.9 percentage points; 95% CI, -7.4 to -0.3 percentage points; P = .04; adjusted odds ratio, 0.51; 95% CI, 0.24-1.07; P = .08), meeting noninferiority. False-positive clinical management decisions occurred in 24 of 287 community participants (8.4%) vs 12 of 348 hospital participants (3.5%) (risk difference, 4.9 percentage points; 95% CI, 0.9-9.0 percentage points). Findings were consistent across per-protocol, cluster-adjusted, and relative risk sensitivity analyses. No adverse event-related withdrawals occurred.Conclusions and RelevanceIn this randomized clinical trial, community optometrist-led monitoring of quiescent nAMD was noninferior to hospital monitoring for detecting disease activity requiring treatment. These results provide evidence for its use in integrated clinical care models.Trial RegistrationClinicalTrials.gov Identifier: NCT03893474

Introduction Cardiac allograft vasculopathy (CAV) is a critical predictor of the long-term success of heart transplantation and once it is established, progression to graft dysfunction and loss is inevitable, despite adherence to immunosuppression and medications that ameliorate cardiac risk factors. Regulatory T cells (Tregs) are key for maintaining immune balance in the periphery. Studies investigating adoptive transfer of ex vivo expanded Tregs isolated from blood have been shown to be feasible and safe with good evidence for Tregs reducing CAV lesions in animal models of transplantation. Here, we describe the protocol for the ATT-Heart Study which is a phase I clinical trial investigating autologous thymus-derived Treg cell therapy in nine paediatric heart transplant recipients.Methods and analysis Patients will be recruited from the heart transplant waiting list at Great Ormond Street Hospital. Individualised autologous thymus-derived and expanded Tregs (TR006) will be injected into patients 3–6 months after transplant and follow-up will be conducted as per the post-transplant standard of care protocol with no wean of standard of care immunosuppression. Primary endpoint includes occurrence of Dose-limiting Toxicities in patients receiving TR006. Further data from blood tests, endomyocardial biopsy tissue, coronary imaging and clinical follow-up will be collected.Ethics and dissemination This article is based on the ATT-Heart study Protocol (V.1.1; dated 19 December 2024). The ATT-Heart trial has received a favourable ethical opinion from the Health Research Authority and South-Central Oxford A Research Ethics Committee (IRAS Number: 1008875/REC reference: 24/SC/0333). Clinical trials authorisation approval from UK Medicines and Healthcare products Regulatory Agency has also been received. The clinical trial will be conducted in accordance with the principles of Good Clinical Practice and following the guidelines set as part of the Research Governance Framework for Health and Social Care and all applicable necessary local policies. It is intended that the findings of the clinical trial will be presented at national/international conferences and using social media and through patient groups for dissemination among their members. The results will also be published in international peer-reviewed journals.Trial registration number ISRCTN15374803.

BACKGROUND:Previous evidence on sex differences in stroke care and outcomes was limited in sample representativeness and coverage of care indicators. We aim to investigate various indicators of stroke care quality, survival, and functional outcome at discharge between men and women, using a national stroke registry. METHODS:Ten key indicators, representative from across stroke care pathway, were compared between men and women using the Sentinel Stroke National Audit Programme, a national quality register for England, Wales, and Northern Ireland (2013-2023, n=844 970). Multivariable Poisson regression models with robust variance were constructed to estimated adjusted relative risks (ARR). The 1-year adjusted hazard ratios (AHR) of mortality were conducted using adjusted restricted mean survival time. Favorable functional outcomes at discharge were measured using modified Rankin Scale (0-2). RESULTS:Women comprised 48% of the study population, mean age 77 years (SD: 13.4) compared with 72 years (13.3) for men. Compared with men, women tend to have severe strokes (19% versus 12%), lower prevalence of diabetes (20% versus 24%), and higher prevalence of atrial fibrillation (21% versus 18%) but similar stroke types (ischemic: 87% versus 88%). Women were less likely to have thrombolysis of arrival <1 hour, brain scan <1 hour, thrombolysis of stroke onset <4 hours, swallowing screen <4 hours, admission to stroke unit <4 hours, assessed by trained nurses <24 hours, assessed by occupational therapist <72 hours, and communication speech and language therapy <72 hours. Women tended to have poorer functional outcome at discharge (ARR, 1.06 [95% CI, 1.05-1.06]) but better 1-year survival (AHR, 0.99 [95% CI, 0.98-0.99]). CONCLUSIONS:Women were less likely to receive several indicators of evidence-based stroke care compared with men. Although they had better survival, functional outcome was poorer in women.

Background Telemedicine can support integrated care between community and hospital services for disease management, potentially enhanced by medical artificial intelligence (AI). Common retinal disease exemplifies this opportunity. Optometry-to-hospital referral pathways generate unnecessary visits, exacerbating hospital pressures. Evidence for the effectiveness of teleophthalmology and AI in optimising these pathways is scarce. Methods This cluster randomised controlled trial was done at optometry practices that referred to four hospital sites in the UK and that were randomly assigned (1:1) to standard care or teleophthalmology using random permuted blocks of varying sizes stratified by hospital site. Statisticians were masked to group assignment for the primary analysis. Individuals aged 18 years or older with suspected macular disease and good quality optical coherence tomography (OCT) scans were included; same-day emergency cases were excluded. In the teleophthalmology group, OCT scans were remotely reviewed by hospital clinicians; the standard care group followed standard referral pathways. The primary outcome was false-positive referral rate (unnecessary overall or urgent [ie, <2 weeks] referrals) against an independent reference standard, analysed in the enrolled and referred populations (superiority margin 30%) using a modified intention-to-treat analysis. A parallel prospective, observational, diagnostic accuracy (validation) study evaluated automated referral recommendations by the Moorfields-DeepMind-AI model, assessing sensitivity and specificity. This trial is registered with ISRCTN.com (ISRCTN18106677) and is closed. Findings Between Jan 26, 2021, and Dec 14, 2022, 71 optometry sites were assessed for eligibility and 26 recruited and randomly assigned to standard care (13 sites) or teleophthalmology (13 sites). Between July 5, 2021, and March 31, 2023, 304 participants were recruited, of whom 294 were included in the analysis (136 in the standard care group and 158 in the teleophthalmology group; 127 [43%] of 294 participants were male, and 167 [57%] were female). Among all enrolled participants, false-positive referrals occurred in ten (7%) of 136 participants in the standard care group versus two (1%) of 158 in the teleophthalmology group (absolute difference 6% [95% CI –5 to 17]; odds ratio [OR] 6·16 [95% CI 1·28 to 58·80]; p=0·018); urgent false-positive referrals occurred in 24 (18%) of 136 versus one (1%) of 158 (17% [11 to 24]; OR 33·37 [5·28 to 1392·05]; p=0·0004). In referred participants only, false-positive referrals occurred in ten (8%) of 125 versus two (2%) of 124 (6% [–5 to 18]; OR 5·27 [1·09 to 50·52]; p=0·035); urgent false-positive referrals occurred in 24 (63%) of 38 versus one (4%) of 27 (59% [41 to 78]; OR 42·00 [5·69–1901·06]; p=0·0001). The superiority margin of a 30% reduction in false-positive referrals was met only for urgent referred cases. Moorfields-DeepMind-AI could process images from 204 (52%) of 396 participants with sensitivity and specificity of 96% (95% CI 92–99) and 20% (8–37), respectively, for all referrals, and 74% (54–89) and 90% (85–94), respectively, for urgent referrals. No serious adverse events occurred. Interpretation Teleophthalmology significantly reduced unnecessary urgent hospital referrals, the main source of capacity pressure in retinal care, demonstrating superiority among referred participants and supporting timely, safe care. Its impact on overall unnecessary referrals was inconclusive due to the low number of non-referred participants. When evaluable (in ∼50% participants), Moorfields-DeepMind-AI recommended more unnecessary referrals overall than clinically indicated. Simulating human experts, AI performed worse than hospital specialists in the teleophthalmology pathway, and similarly to community optometrists in standard care, probably reflecting differences between clinician judgement and fixed AI rules. Funding National Institute for Health and Care Research.

Introduction Patients recovering from severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a 30-day readmission rate of 20%. This study evaluated the feasibility of conducting a randomised controlled trial to evaluate clinical, patient-reported and physiological effects of home high-flow therapy (HFT) in addition to usual medical therapy, in eucapnic patients recovering from AECOPD to support the design of a phase 3 trial.Methods A mixed-methods feasibility randomised controlled trial (quantitative primacy, concurrently embedded qualitative evaluation) (ISRCTN15949009) recruiting consecutive non-obese patients hospitalised with AECOPD not requiring acute non-invasive ventilation. Participants were randomised to receive usual care or usual care and home HFT (37°C, 30 L/min) with weekly home-based follow-up for 4 weeks to collect data on: device usage, breathlessness (modified Borg scale, visual analogue scale, Multidimensional Dyspnoea Profile), health-related quality of life (COPD Assessment Test (CAT), Clinical COPD Questionnaire), pulse oximetry, spirometry and inspiratory capacity, parasternal electromyography and actigraphy. Semistructured interviews were conducted in week 4. Trial progression criteria were: ≥40% of eligible patients randomised, ≤20% attrition, ≥70% complete data, and no device-related serious adverse events (SAE).Results 18 of 45 eligible patients were randomised (age 69±5 years, 44% female, body mass index 23±5 kg/m2, forced expiratory volume in 1 second 32±12%). One withdrew following non-respiratory hospitalisation. Complete outcome measures were collected in >90% of home assessments. There were no device-related SAE. Daily HFT usage was 2.7±2.2 hours in week 1, falling to 2.3±1.4 hours by week 4. Temperature and flow settings were modified for comfort in 6 cases. Higher HFT usage was associated with lower symptom burden (CAT p=0.01). Interviews highlighted ease of device use, reduced salbutamol usage, and improved sputum production and clearance.Conclusions The data from this feasibility study support the progression to a phase 3 randomised clinical trial investigating the effect of home (HFT) on admission-free survival in COPD patients recovering from a severe exacerbation.Trial registration number The study received ethical approval (REC19/LO/0194) and was prospectively registered (ISRCTN15949009).

Advanced HNSCC has a dismal prognosis despite multiagent treatment. Epidermal growth factor receptor (EGFR, ErbB-1) is upregulated in most tumors, although EGFR-targeted therapy yields modest benefit. Other ErbB family members are commonly co-expressed, providing a rationale for targeting of the extended ErbB network in HNSCC. We present final toxicity and response data for this FIH dose escalation trial of intratumorally administered pan-ErbB-targeting CAR-T cells (T4 immunotherapy) in patients (pts) with advanced HNSCC. Eligible pts had locally advanced, recurrent or metastatic HNSCC (excluding brain), accessible tumor site(s) for T4 administration and radiologically measurable disease. Peripherally harvested T cells were transduced to co-express pan-ErbB-targeting CAR T1E28ζ and chimeric IL-4/IL-2 receptor 4αβ. Cells were expanded ex vivo in IL-4 to generate T4 immunotherapy, which was injected as a fresh product into single or multiple locoregional tumor sites. Doses ranged from 1×107 to 1×109 cells across 7 cohorts, using 3+3 dose escalation in cohorts 1-5. Cohorts 6 and 7 received 1×108 cells preceded by lymphodepleting (LD) cyclophosphamide and fludarabine chemotherapy. Cohort 7 received additional nivolumab 480mg q4w for 3 cycles. Primary endpoint was dose limiting toxicity (DLT) within 28d. Secondary endpoints included radiologic response at 6w, presence of tumoral and circulating T4+ T cells and serum and tumoral immunomodulatory markers. 19 pts (median age, 62; M:F,15:4) received T4 immunotherapy: 3 in each cohort 1-6 and 1 in cohort 7. Site of origin was oral cavity in 11 (57.9%), oropharynx, 4 (21.1%); nasopharynx, 2 (10.5%); hypopharynx and occult primary 1 each (5.3%). Pts had received a median of 2 (1-5) prior treatment lines. No DLTs were observed. All pts experienced TRAEs, largely G1/2; most common were local swelling, pain or infection, fever, CRS, chills, fatigue and nausea, with cytopenias in LD cohorts. Of 4 instances of CRS, 3 were G1 and 1 was G2. At 6 weeks, 10 pts (52.6%) had stable disease and 9 (47.4%) had progressed, with no association with T4 dose, LD or nivolumab. There were no radiologic responses though softer tumor consistency was noted in several pts. Median overall survival (mOS) was >10m. Subsequent treatments included palliative radiotherapy, chemotherapy +/- cetuximab, electrochemotherapy or trial in 8 pts; no treatment, 4; unknown, 3. One pt had a durable complete response to subsequent local injection of talimogene laherparepvec with pembrolizumab. Intratumoral pan-ErbB-directed CAR-T cell injection was well tolerated and associated with disease stability in heavily pretreated HNSCC. mOS was longer than that expected for this cohort. The lack of radiologic responses highlights the need for improved advanced cell therapies for solid tumors. Cienne Morton, Fiona Wang, Sophie Papa, Antonella Adami, Michael Metoudi, Daniela Achkova, Fiona Reid, Maria Elstad, Nicholas Beckley-Hoelscher, Abdel Douiri, Marc Delord, Mike Lyne, Dharshene Shivapatham, Aysar Al-Rawi, Christopher Fisher, Andrew Hope, Sakina Gooljar, Arindam Mitra, Linda Gomm, Ana C. Parente-Pareira, David M. Davies, Farzin Farzaneh, Teresa Guerrero-Urbano, Jean-Pierre Jeannon, James Spicer, John Maher. Final results of a first-in-human (FIH) study of intratumoral pan-ErbB-targeted CAR-T cell therapy for head and neck squamous cell carcinoma (HNSCC): T4 immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT058.

OBJECTIVES:The gastrointestinal tract (GIT) is a reservoir of multidrug-resistant organisms (MDRO). Colonisation with MDRO precedes invasive infections, which can be challenging to treat with excess morbidity and mortality compared to antimicrobial-susceptible infections. Currently, there are no effective GIT decolonisation strategies. Whilst faecal microbiota transplant (FMT) has emerged as a potential therapeutic, there remains uncertainty about its feasibility, safety, and efficacy. METHODS:Population: Patients with invasive infection with extended-spectrum beta-lactamase (ESBL-) or carbapenem-resistant Enterobacterales (CRE) and persistent GIT carriage. INTERVENTION:Three doses of encapsulated lyophilised FMT. COMPARATOR:Matched placebo capsules. OUTCOMES:Primary outcome was participant consent rate as a proportion of those approached to be screened for GIT carriage of ESBL-E/CRE. Secondary outcomes were additional feasibility, safety and tolerability, and efficacy metrics. Exploratory outcomes included stool metagenomic analysis. RESULTS:Of 460 approached individuals, 124 (27%) consented. 53/124 participants (43%) fulfilled all eligibility criteria. 44/53 (83%) of those eligible were randomised and 41/44 (93%) received investigational medicinal product (IMP): 20 FMT and 21 placebo. 39/41 (95%) completed IMP dosing. Abdominal bloating and skin and subcutaneous tissue disorders were more common following FMT, but there were no unanticipated harms. MDRO carriage decreased over time across arms but was lower at all time points in the FMT arm. FMT increased microbiome diversity and microbiome-based health measures. FMT recipients' samples clustered into two groups, with those with more dissimilar community composition to donors more likely to decolonise post-FMT (3/5 vs. 0/12, p = 0.01). Patients that decolonised exhibited a trend towards increased proportional representation of donor-derived strains in their post-FMT samples (p = 0.05) and change in strain dominance within MDRO at the species-level. CONCLUSIONS:Progression to a substantive trial is feasible with modifications to the existing FERARO protocol. FMT was safe, well tolerated, and acceptable to patients colonised with MDRO. Microbiome analysis infers that greater donor-recipient microbiome dissimilarity at baseline and higher rates of donor-derived strain engraftment favour MDRO decolonisation, which in turn maybe facilitated by conspecific strain replacement.