Background:High levels of smoking among people who experience imprisonment contribute to their high mortality and morbidity rates and to inequalities. Scotland's prisons became smokefree in 2018. However, questions remain about how to prevent high relapse to smoking post release. Objectives:Summarise evidence on supporting people to reduce tobacco-related harms post release. Understand experiences, opportunities and challenges for reducing tobacco-related harms for people leaving smokefree prisons and for families. Feasibility test a household-targeted intervention to support people released from smokefree prisons to reduce tobacco-related harms. Update cost-effectiveness of smokefree prison policy. Partnership-working with key stakeholders. Design and methods:Scoping reviews; qualitative; health economic modelling. Setting/participants:Prisons in Scotland; staff, people in prison, family members. Results:Our scoping reviews show that evidence on interventions to support people leaving smokefree prisons to remain tobacco-free is weak. There is no evidence on smoking rates among people released from smokefree prisons allowing vaping. Significant barriers remain for people from underserved communities to create smokefree homes. Our modelling highlights that offering effective smoking cessation support to people leaving smokefree prisons would be cost saving at both the personal and societal levels. The challenges people face on release from prison and variability in throughcare support often render smoking relapse prevention a low priority for them, their families and service providers. However, in terms of long-term prevention of ill health and premature death, the high rates of relapse to smoking (~50-80%) continue to fuel inequalities. Supporting people leaving smokefree prisons to remain abstinent will help governments to achieve ambitions to create smokefree societies. Progress may be achieved by greater integration of support for tobacco-harm reduction with services addressing interconnected needs, such as harmful use of other substances and underlying mental ill health. Limitations:The extensive impact of coronavirus disease discovered in 2019 in prisons into 2023, alongside challenges due to overcrowding and staffing pressures, limited the opportunities for partnership working and the number of interviews we could conduct. This meant that we were unable to test the feasibility of delivering a household-based intervention to reduce tobacco-related harms in this population. Conclusions:Progress in developing suitable interventions to prevent very high relapse-to-smoking rates following release from smokefree prisons is required. Helping people released from smokefree prisons to remain abstinent from tobacco post release could deliver considerable benefits. However, in the face of substantial challenges, preventing relapse to smoking has become entrenched as a low priority - for many service providers, people leaving smokefree prisons and their families. Greater success in reducing tobacco-related harms among this often-overlooked population may be achieved through more holistic models of service delivery. Aspirations for countries to become tobacco-free may require a rethink of what is needed to support underserved populations in whom smoking remains entrenched. Future work:Further research is required to better understand what approaches are feasible and effective for maintaining smoking abstinence following release from prison, including development and evaluation of integrated/holistic approaches which tackle smoking/vaping behaviours in the context of use of other substances and needs. Funding:This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Public Health Research programme as award number NIHR131613.

Schizophrenia (SCZ) is a highly polygenic disorder and is associated with several comorbidities, including depression, cardiovascular disease, and diabetes; yet the biological pathways underlying this clustering remain poorly understood. This study examined associations between a polygenic risk score for SCZ (PRS-SCZ) and circulating protein levels in 44,661 participants of the UK Biobank. We assessed 1,459 proteins (with ≤ 10% missingness) spanning neurological, inflammatory, cardiometabolic, and oncology panels. After adjustment for technical (population structure, genotyping chip), individual (age, sex, lifestyle), and clinical (comorbidities and medication) variables and multiple testing correction, the standardised PRS-SCZ was significantly negatively associated with C2, RNASET2, BTN2A1, CDSN, HLAE, LTA, MICA-MICB, CNTN3, FCER2, INHBC and CPVL concentrations, and positively with ICAM3, BTN3A2, IL5RA, SLAM7 concentrations. These protein biomarkers may provide insights into the biological pathways underlying schizophrenia and/or its comorbidities.

Body mass index (BMI) is widely used to assess obesity-related risk, but it does not capture ectopic fat deposition. Muscle fat infiltration (MFI), an MRI-derived marker of ectopic adiposity, may provide additional insight into type 2 diabetes (T2D) risk (1) . We examined sex-specific associations of MFI and BMI with incident T2D in a large population-based cohort. This prospective analysis included 17,482 women and 19,610 men free of T2D at baseline with available MRI data. Incident T2D cases (468 in women and 270 in men) were identified using linked primary care records, with a median follow-up of 12.1 years. BMI and MRI-derived MFI were standardized (z-scores) and additionally categorized into sex-specific quintiles. Sex-stratified Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) per 1-SD increase and across quintiles, adjusting for age, deprivation index, ethnicity, physical activity, smoking status, and alcohol intake. For a 1-SD increase in MFI, the risk of T2D was higher in both women (HR: 1.53; 95% CI: 1.42–1.64) and men (HR: 1.49; 95% CI: 1.41–1.57). Corresponding associations for BMI were stronger (women: HR 2.10; 95% CI: 1.93–2.28; men: HR 2.06; 95% CI: 1.93–2.20). Comparing the highest versus lowest quintile, women in the highest BMI quintile had a markedly higher risk of T2D (HR: 19.5; 95% CI: 9.12–41.6), while the highest quintile of MFI was associated with a 9.07-fold higher risk (95% CI: 4.54–18.1). Among men, the highest quintile of MFI was associated with an 8.35-fold higher risk (95% CI: 5.33–13.1), whereas the highest quintile of BMI was associated with an 11.5-fold higher risk (95% CI: 7.33–18.0). Muscle fat infiltration, an MRI-derived marker of ectopic adiposity, is strongly associated with future risk of type 2 diabetes in both women and men. However, BMI showed consistently stronger associations with T2D risk, particularly at the extremes of the distribution. These findings suggest that while MRI-derived measures such as MFI capture important aspects of metabolic risk, BMI remains a robust and powerful predictor of T2D in population settings. Advanced imaging may nevertheless offer complementary value for understanding ectopic fat–related mechanisms and refining risk stratification.

Objective:To determine the effectiveness of mobile health augmented cardiac rehabilitation on clinical factors among post-acute coronary syndrome (post-ACS) patients. Method:A randomized controlled trial was conducted at Armed Forces Institute of Cardiology, Rawalpindi. This study was conducted on inpatients post-ACS patients. Patients were randomly allocated into the intervention group (counselling, short text messages, and standard post-ACS care) or the control group (standard post-ACS care). Clinical factors assessed were blood pressure, body mass index, the number of days of hospitalization, no of readmissions, and major adverse clinical events (MACE) within 180 days post-ACS. Data were collected thrice for six months follow-up periods (baseline, 12 and 24 weeks). Result:The mean days of hospitalization were reduced significantly of the intervention group compared to the control group (02.55, 95%CI: 02.13, 02.98 versus 04.07, 95%CI: 02.96, 05.17, p-value=0.033) at 12 weeks follow up. Also, at 24 weeks follow up, the intervention group reduced the number of readmission days compared to the control group (02.62, 95% CI: 02.00, 03.24, versus 03.71, 95%CI: 02.68, 04.74, p-value=0.041). Twenty-nine (43.94%) patients of the control group and 18 (24.32%) of the intervention group developed MACE at 12 weeks follow up (p-value: 0.016). While at 24 weeks follow up, 8 (16.33%) of the control group and 7 (9.86%) of the intervention group suffered MACE (p-value: 0.196). Conclusion:The MCard positively impacts the clinical outcomes. It has significantly decreased the likelihood of readmission and decreased the number of days of hospitalization among the MCard group compared to the usual care group. This trial has found an overall lower incidence of MACE (composite of readmission, myocardial re-infarction, heart failure and death) among the MCard group than usual care. Registration: Australian New Zealand Clinical Trial Registry (ANZCTR) (ACTRN12619001731189).16.

BACKGROUND:Transformer-based neural networks excel in modelling high-dimensional, time-series data with complex dependencies. This proof-of-concept study applies a transformer-X-learner framework to estimate treatment effects using real-world data, using antihypertensive drug exposure and COVID-19 risk as an exemplar. METHODS:We conducted a case-control study of 303,220 NHS Greater Glasgow and Clyde patients aged ≥ 40 years during the first two COVID-19 pandemic waves. Using a transformer-X-learner framework that incorporated temporal patterns in medication usage and comorbidities, we controlled for confounding effects and estimated individual and average treatment effects ACEIs, beta-blockers (BBs), calcium channel blockers (CCBs), thiazides (THZs), and statins on 180-day SARS-CoV-2 infection risk. RESULTS:The transformer-X-learner framework outperformed traditional approaches, achieving an F1 score of 0.82 and area under the precision-recall curve (AUPRC) of 0.78. ACEIs showed a negligible overall impact on COVID-19 risk (ATE: 0.97%±5.5), while BBs (-8.3%±7.3%) and CCBs (-9.7%±8.1%) were protective. Statins (3.5%±6.1%) and THZs (4.3%±10.8%) showed slight increases in risk. Treatment effects were consistent across age, gender, and socioeconomic categories. CONCLUSIONS:ACEIs do not substantially increase the risk of COVID-19 infection while the protective effects of BBs and CCBs warrant further investigation. This study highlights the potential of transformer-based causal inference models as a powerful tool for evaluating treatment safety and efficacy in complex healthcare scenarios.

The associations between systemic inflammation biomarkers and cardiovascular disease (CVD) remain not well explored. This study aimed to investigate associations between different systemic inflammation biomarkers and incident CVD and main CVD subtypes - ischaemic heart disease (IHD), stroke, and heart failure - explore dose–response relationships, and compare their predictive performance. This prospective cohort study included 423,701 UK Biobank participants free of CVD at baseline. Baseline neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and system inflammation response index (SIRI) were derived. Cox-proportional regression models were used to investigate the associations. NLR, PLR, SII, and SIRI was positively and LMR was negatively associated with all four of the outcomes investigated. The relationships were non-linear for all biomarkers with CVD and were linear for NLR, SII, and SIRI and non-linear for LMR and PLR with IHD, stroke and heart failure. Compared with the more established biomarkers, all four of the novel biomarkers had statistically superior predictive performance for three of the outcomes investigated (CVD, IHD and heart failure) and three of them were superior at predicting stroke. Compared to a model of CVD prediction with classical risk factors (C-index = 0.702), discrimination was improved on the addition of inflammation markers for CVD (C-index change 0.0069, 95

BACKGROUND:Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial regulator of cholesterol metabolism. Loss-of-function variants in PCSK9 are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and reduced cardiovascular disease (CVD) risk, while gain-of-function variants correlate with elevated LDL-C concentrations and increased CVD risk. This study investigated whether genetically determined LDL-C levels, proxied by four PCSK9 genetic variants, influence common carotid artery atherosclerosis. METHODS:The analysis included 3040 European participants (mean age 64.2±5.4 years; 45.8% men) at high cardiovascular risk from the IMPROVE Study, alongside 49 088 individuals of white British ancestry (mean age 55.2±7.6 years; 47.9% men) from the UK Biobank (UKB). Ultrasonographic measurements of common carotid intima-media thickness (CC-IMTmean, CC-IMTmax, CC-IMTmean-max) were obtained. Four lipid-level affecting genetic variants in the PCSK9 locus were selected for analysis, both individually and in a standardised Lipid-Lowering Allelic Score (LLAS), to assess their effects on LDL-C and PCSK9 levels in the IMPROVE cohort and on ultrasonographic measures in both IMPROVE and UKB. RESULTS:In the IMPROVE cohort, PCSK9 variants (rs11206510, rs2479409, rs11591147, rs11583680) exhibited expected effect directions, although not all statistically significant, on LDL-C and PCSK9 levels. The LLAS was negatively correlated with CC-IMTmean, CC-IMTmax and CC-IMTmean-max among women in IMPROVE, and among men and overall in UKB (all p<0.05). Effect sizes were comparable between cohorts. CONCLUSIONS:Genetic variants in the PCSK9 locus influence LDL-C levels and CC-IMT, in keeping with proven benefits of PCSK9 inhibitors on atherosclerotic cardiovascular events.

Importance:History of traumatic brain injury (TBI) or repetitive head impacts is associated with an increased risk of neurodegenerative disease. This association has attracted attention in recent years through the relationship between contact sports participation and the increased risk of a number of neurodegenerative diseases, including motor neuron disease or amyotrophic lateral sclerosis (ALS). However, to date, the association between TBI in the community and ALS risk remains uncertain. Objective:To leverage population-level health records to explore the association between a history of TBI and subsequent ALS risk. Design, Setting, and Participants:This retrospective cohort study accessed UK-wide electronic health record (EHR) data from individuals 18 years or older with TBI history and age-, sex-, and area deprivation-matched general population comparators. EHR data were available from January 1, 2005, to December 31, 2020, with database interrogation performed on February 11, 2021, and data analysis conducted between June 1, 2023, and October 3, 2024. Exposure:Documented history of TBI. Main Outcomes and Measures:Outcomes were obtained by individual-level linkage to EHR data available via Clinical Practice Research Datalink. Risk of ALS was evaluated using Cox proportional hazards regression models to investigate its association with TBI. Results:Overall, 85 690 adults with a history of TBI and 257 070 matched adults with no history of TBI were included, for a total of 342 760 participants (50.1% male; mean [SD] age, 50.7 [17.6] years). During a median 5.72 (IQR, 3.07-8.82) years of follow-up, providing 2.13 million person-years of follow-up, 150 incident ALS cases were recorded, resulting in 7.05 cases per 100 000 person-years. Risk of ALS was higher among individuals with a history of TBI compared with individuals without a TBI history (hazard ratio [HR], 2.61; 95% CI, 1.88-3.63). However, this association was time dependent, with risk confined to the 2 years following TBI (HR, 6.18; 95% CI, 3.47-11.00), but not thereafter. Conclusions and Relevance:In this retrospective cohort study of 342 760 adults, an association between TBI and subsequent risk of ALS was identified. However, this association was confined to the 2 years immediately following injury. As such, the association between TBI and higher ALS risk may indicate reverse causality, with TBI in some individuals perhaps reflecting a consequence of early, subclinical ALS.

BACKGROUND:NICE guidelines recommend GPs use the kidney failure risk equation (KFRE) to identify people with chronic kidney disease (CKD) at higher risk of kidney failure. Albuminuria results are required to calculate KFRE. AIM:Analyse the implementation of KFRE into clinical practice and investigate if albuminuria testing varied amongst patients with CKD, particularly for underserved groups. DESIGN AND SETTING:Retrospective cohort study of 23,063 adults in Glasgow from 2013 to 2022. METHOD:We evaluated albuminuria testing rates and the predictive performance of KFRE in estimating 5-year kidney failure risk amongst people with CKD. Logistic regression models quantified associations between demographic/clinical variables and albuminuria testing. Amongst people who developed kidney failure, we retrospectively assessed the impact of KFRE on the timing of meeting criteria for referral to renal services. RESULTS:Albuminuria testing was performed in 44.5% of 10,874 adults with CKD. Females (adjusted odds ratio (aOR) 0.86: 95% CI 0.79-0.93) and those with hypertension (aOR 0.69: 95% CI 0.63-0.77) were less likely to have albuminuria testing. Those aged 40-50 years (aOR 1.83: 95% CI 1.15-2.91), with diabetes (aOR 2.35: 95% CI 2.14-2.58) and living in the least socioeconomically deprived areas (aOR 1.11: 95% CI 1.00-1.23) were more likely to have albuminuria testing. Of 1,352 individuals with incident kidney failure, incorporating KFRE into referral guidelines helped identify high-risk patients early. CONCLUSION:KFRE could be calculated for less than half of people due to lack of albuminuria testing. Focus should be given to improving albuminuria testing and inequities identified to allow wider implementation of KFRE.

Background and aims: Circulating PCSK9 is a crucial regulator of cholesterol metabolism. Loss-of-function variants in PCSK9 are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and reduced cardiovascular disease (CVD) risk, while gain-of-function variants correlate with elevated LDL-C concentrations and increased CVD risk. This study investigated whether genetically determined LDL-C levels, proxied by four PCSK9 genetic variants, influence common carotid artery atherosclerosis. Methods: The analysis included 3,040 European participants (mean age 64.2 {plus minus} 5.4 years; 45.8% men) at high cardiovascular risk from the IMPROVE study, alongside 49,088 individuals of white British ancestry (mean age 55.2 {plus minus} 7.6 years; 47.9% men) from the UK Biobank (UKB). Ultrasonographic measurements of common carotid intima-media thickness (CC-IMTmean, CC-IMTmax, CC-IMTmean-max) were obtained. Four lipid-level affecting genetic variants in the PCSK9 locus were selected for analysis, both individually and in a standardized polygenic risk score (PRS), to assess their effects on LDL-C and PCSK9 levels in the IMPROVE cohort and on ultrasonographic measures in both IMPROVE and UKB. Results: In the IMPROVE cohort, PCSK9 variants (rs11206510, rs2479409, rs11591147, rs11583680) exhibited expected effect directions, albeit not all statistically significant, on LDL-C and PCSK9 levels. The PRS was negatively correlated with CC-IMTmean, CC-IMTmax, and CC-IMTmean-max among women in IMPROVE, and among men and overall in UKB (all P < 0.05). Effect sizes were comparable between cohorts. Conclusions: Genetic variants in the PCSK9 locus influence LDL-C levels and CC-IMT, in keeping with proven benefits of PCSK9 inhibitors on atherosclerotic cardiovascular events. ### Competing Interest Statement A.Gallo has received honoraria related to consulting, research, and or speaker activities from Amarin, Amryt, Amgen, Astrazeneca, Eli-Lilly, MSD, Novo-Nordisk, Novartis, Sanofi/Regeneron, Servier, Viatris and Ultragenyx. P. Welsh declares grant support from Astrazeneca, Roche diagnostics, Boehringer Ingelheim, and Novartis outside the submitted work and honoraria from Novo Nordisk and Raisio outside the submitted work. N. Sattar reports consulting/speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and institutional research support from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics D. Coggi, J. Ward, B. Gigante, M. Amato, D.M. Lyall, B. Frigerio, A. Ravani, D. Sansaro, F. Veglia, N. Capra, K. Savonen, M. Pirro, D.J. Mulder, N. Ferri, M.G. Lupo, C. Macchi, M. Ruscica, R. Baetta, E. Tremoli, D. Baldassarre and R.J. Strawbridge declare no conflict of interest. ### Funding Statement At least in part, this study uses data derived from a project funded by the European Commission, Fifth Framework Programme (Contract number: QLG1-CT-2002-00896; to E. Tremoli, D. Baldassarre) and by the Ministry of Health, Italy (RC2018 MMP4.9 ID: 2634520; RC2019 MPP 4D ID: 2755475; to D. Baldassarre). The UKB was founded by the Wellcome Trust, Medical Research Council, Department of Health, Scottish Government and Northwest Regional Development Agency. UKB was also funded by the Welsh Assembly Government and the British Heart Foundation. Data collection was supported by UKB. R.J. Strawbridge is supported by a UKRI Innovation-HDR-UK (MR/S003061/1) and the University of Glasgow Lord Kelvin Adam Smith Fellowships. The funders were not involved in the interpretation or presentation of the findings. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The IMPROVE study complies with the rules of Good Clinical Practice and with the ethical principles established in the Declaration of Helsinki, and was approved by 6 independent ethics committees, i.e.: the Regional Ethics Review Board at Karolinska Institutet, Stockholm, Sweden (approval ID: Dnr 2003/03-115, 17 February 2003); the Institutional Review Board of the Health Department of the Hospital "Ospedale Niguarda Ca' Granda", Milan, Italy (approval ID: 2042/03, 3 June 2003); the Medical Ethics Review Committee, Academic Hospital Groningen, Groningen, the Netherlands (approval ID: METc 2003/054, 12 May 2003); the Ethics Committee of the Umbrian Health Authorities, Perugia, Italy (approval ID: N 2725/03/A, 6 February 2003); the Consultative Committee for the Protection of Persons in Biomedical Research (CCPPRB) at Hôspital Pitie Salpétrière, Paris, France (approval ID: CCP61-03, 2003); the Research Ethics Committee of the University of Kuopio and Kuopio University Hospital, Kuopio, Finland (approval ID: 140/2002, 10 October 2002). All patients provided informed consent twice; once for general participation in the study and once for genotyping. All participants in UKB provided informed electronic consent and UKB was granted ethical approval by the North-West Multicentre Research Ethics Committee on the 29th of June 2021 (Ref 21/NW/0157). This study was conducted under project #71392, (P.I. Strawbridge). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes UKB data is available via application to UKB (https://www.ukbiobank.ac.uk/). IMPROVE is not available for sharing. Analytic code is available upon request from the corresponding author.

AIMS:Genetic predisposition to adiposity is associated with type 2 diabetes (T2D), even in the absence of phenotypic adiposity (obesity and central obesity). We aimed to quantify the overall contribution of obesity and modifiable lifestyle factors to the association between genetic predisposition to adiposity and the development of T2D. METHODS:This prospective cohort study involved 220 703 White British participants from the UK Biobank. It examined the associations between genetic predisposition to adiposity [body mass index polygenic risk (BMI-PRS) and waist-hip ratio polygenic risk (WHR-PRS)] and incident T2D, as well as interactions and mediation via lifestyle factors (diet quality, physical activity levels, total energy intake, sleep duration, and smoking and alcohol intake) and phenotypic adiposity. RESULTS:People with high phenotypic adiposity and high adiposity PRS values (>1 SD above the mean) had the highest risk of incident T2D (versus non-obese/central obese and non-high PRS). This was the case for BMI-PRS [hazard ratio (HR) = 3.72] and WHR-PRS (HR = 4.17). Lifestyle factors explained 30.5% of the BMI-PRS/T2D association (2.0% mediation; 28.5% effect modification), and lifestyle and obesity together explained 92.1% (78.8% mediation; 13.3% effect modification). Lifestyle factors explained 20.4% of the WHR-PRS/T2D association (3.4% mediation; 17.0% effect modification), and lifestyle and central obesity together explained 72.8% (41.1% mediation; 31.7% effect modification). CONCLUSIONS:Whilst phenotypic adiposity explains a large proportion of the association between BMI-PRS/WHR-PRS and T2D, modifiable lifestyle factors also make contributions. Promoting healthy lifestyles among people prone to adiposity is important in reducing the global burden of T2D.

Physical activity (PA) is consistently associated with lower risk of long-term conditions. Preliminary evidence suggested the associations could be modified by air pollution. This study aims to examine whether air pollution levels modify the associations of PA with all-cause mortality and incident cancer, major adverse cardiovascular events (MACE), type 2 diabetes, and chronic obstructive pulmonary disease (COPD). A total of 414,644 UK Biobank participants were included in the analyses. PA was self-reported and objectively measured using accelerometers. PA was self-reported with IPAQ and objectively measured using accelerometers. Annual PM2.5, PM10, and NO air pollutant concentrations in 2010 were measured using a European land use regression model. Cox proportional hazard models were used to examine the associations of PA and air pollution with health outcomes. Multiplicative and additive interactions were estimated. During the study period from 2006 to 2022, 31,765 (7.7

Current evidence suggests the possibility that autistic people may be at more risk of COVID-19 infection, hospitalisation, and mortality than the general population. Previous studies, however, are either limited in scale or do not investigate potential risk factors. Research into risk factors focused on general population samples. The current study aims to investigate these risk factors in the autistic population. Using data-linkage and a whole-country population, this study modelled associations between autism and COVID-19 hospitalisation and mortality risk in adults, investigating a multitude of clinical and demographic risk factors. Autistic adults had higher rates of hospitalisation, Standardised Incident Ratio 1.6 in 2020 and 1.3 in 2021, and mortality, Standardised Mortality Ratio 1.52 in 2020 and 1.34 in 2021, due to COVID-19 than the general population. In both populations, age, complex multimorbidity and vaccination status were the most significant predictors of COVID-19 hospitalisation and mortality. Effects of psychotropic medication varied by class. Although similar factors exhibited a positive association with heightened risk of severe COVID-19 in both the autistic and general populations, with comparable effect sizes, mortality rates were elevated among the autistic population compared to the general population. Specifically, complex multimorbidity and classification of prescribed medications may emerge as particularly significant predictors of severe COVID-19 among individuals within the autistic population due to higher prevalence of complex multimorbidity in the autistic population and variability in the association between medication classes and severe COVID-19 between both populations, though further research is needed.

AIMS:Pain is associated with cardiovascular disease; however, its association with incident arrhythmias is unclear. We assessed associations between different pain characteristics (pain type, chronic pain, chronic widespread pain [chronic widespread pain], chronic musculoskeletal pain [chronic musculoskeletal pain], and number of chronic pain and chronic musculoskeletal pain sites) and incident cardiac arrhythmias, overall and by subtype. METHODS:The study included 422,654 UK Biobank participants. Pain was ascertained via a touchscreen questionnaire. The outcomes were incident arrhythmias: all cardiac arrhythmias, atrial fibrillation (AF), other (non-AF) cardiac arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Multivariable Cox-proportional regression was used to investigate the associations. RESULTS:Over a mean (SD) follow-up of 13.19 (1.96) years, 36,860 (8.72%) participants developed arrhythmia. Compared with those without pain, those with chronic localized pain and chronic widespread pain had increased risk of all cardiac arrhythmias (hazard ratio [HR] 1.13, 95% confidence interval [CI], 1.10-1.17; 1.34, 1.19-1.51), AF (1.09, 1.05-1.14; 1.33, 1.15-1.55), and other cardiac arrhythmias (1.17, 1.12-1.22; 1.41, 1.20-1.66). There was evidence of a dose-relationship between number of chronic pain sites and risk of all cardiac arrhythmias, AF and bradyarrhythmias. Effect estimates were significantly larger among participants aged <60 years than those aged ≥60 years, and larger in women than men. CONCLUSIONS:Chronic pain was associated with cardiac arrhythmias. Whilst causation cannot be assumed in any observational study, there was evidence of both a temporal relationship and dose-relationship. These findings reinforce the need for pain management approaches that include a broad assessment of individuals' risk factors, wider health status, and appropriate vigilance for emerging conditions.

Background Studies on avoidable mortality in adults with intellectual disabilities are limited, as are studies on causes of death.Objectives We aimed to quantify mortality rates, and causes, and identify factors (i.e., age, sex, Scottish Index of Multiple Deprivation (SIMD)) related to avoidable mortality in adults with intellectual disabilities.Design A record linkage national cohort study.Setting A cohort of adults with intellectual disabilities with or without co-occurring autism, aged 25+ years and a randomly selected comparison group aged 25+ years without intellectual disabilities or autism identified from Scotland’s Census, 2011. Census records were linked to the National Records of Scotland Statutory Register of Deaths database to ascertain all deaths from 2011 to 2019.Participants We analysed data on 14 477 adults with intellectual disabilities aged 25+ years and a randomly selected comparison group of 506 207 adults aged 25+ without intellectual disabilities identified from Scotland’s Census 2011.Primary and secondary outcome measures We ran χ2 tests and t-tests to investigate individual characteristics and differences in age at death for adults with intellectual disabilities compared with peers in the general population. Cox proportional hazard models were fitted to calculate risk of mortality (all-cause, avoidable, treatable, preventable) unadjusted and adjusted for age, sex and SIMD. We then calculated mortality rates, using crude and indirect standardisation methods.Results During the 8.5-year follow-up, 23.7% (crude death rate of 3033.3 per 100 000) of adults with intellectual disabilities died compared with 13.8% of controls. The median age at death among adults aged 25+ with intellectual disabilities was 65.0 years compared with 80.0 years for adults without intellectual disabilities. For all-cause mortality, the age-standardised mortality ratio (SMR) in the population with intellectual disabilities was 3.1 (95% CI 3.0 to 3.2). The SMRs were higher for the youngest age groups, women and in the most affluent areas. This was also the case for SMRs for avoidable, treatable and preventable deaths. For the population of adults with intellectual disabilities, 31.7% of recorded deaths were considered avoidable, 21.1% were treatable and 19.9% were preventable. In the controls, 18.2% of deaths were considered avoidable, 8.8% treatable and 14.7% preventable. Down syndrome and dementia were the two most commonly recorded underlying causes of death for people with intellectual disabilities while malignant neoplasm of bronchus and lung and acute myocardial infarction were most commonly recorded in the general population.Conclusions Risk of all-cause, avoidable, treatable and preventable mortality was higher for adults with intellectual disabilities than their peers. The highest SMRs were observed for youngest adults, women and individuals living in the most affluent areas.

BACKGROUND:Greenspace benefits for cardiovascular disease (CVD) may depend more on quality than proximity, but feature-specific evidence is limited. METHODS:We linked objectively mapped park features to 377,817 urban UK Biobank participants and followed incident CVD (46,474 events) over a median 14.1 years. Network-based walk-distance catchments (400/800/1,600 m) were delineated for each home. We created an "any park" present indicator and feature-specific park indicators (e.g. tree canopy, water, cafes, toilets, attractions, sports) at each distance. Cox proportional hazards mixed-effects models adjusted for sociodemographic covariates, area deprivation, ambient natural landcover, and geographical clustering. Effect modification by sex, area-level deprivation, and age group (<65/≥65) was examined. RESULTS:"Any park" was not associated with CVD, whereas feature-specific models indicated modest protection (≈3-6 % lower hazards). Tree canopy showed the strongest, distance-stable pattern with clearest support for ≥50 % at 800 m (HR 0.941, 95 % CI 0.912-0.992). Water features were protective at 400 m (HR 0.946, 95 % CI 0.907-0.986). Cafes were protective at 800 m (HR 0.971, 95 % CI 0.945-0.999), and 2+ public attractions at 1,600 m (HR 0.977, 95 % CI 0.957-0.997). Sports facilities at 800 m were associated with higher risk (HR 1.028, 95 % CI 1.004-1.057). Effect modification was limited: cafes at 800 m were more protective in high-deprivation areas; ≥50 % canopy at 1,600 m were more protective in women. CONCLUSIONS:What's inside parks matters more than proximity. Higher tree canopy and nearby blue features appear broadly protective, while strategically placed amenities may support engagement.

AIMS:Despite several modifiable risk factors for dementia being identified, diet is often excluded from consideration due to insufficient evidence. Although various healthy dietary indices have been associated with improved health outcomes, their link to dementia risk remains unclear. This study investigates the association between four dietary indices and dementia risk among UK Biobank participants. MATERIALS AND METHODS:This study utilized data from the UK Biobank cohort. Dietary intake was self-reported using repeated 24-h recalls (up to five occasions), averaged for analysis. Adherence to a healthy diet was assessed using four dietary indices: the Recommended Food Score (RFS), Healthy Diet Indicator (HDI), Mediterranean Diet Score (MDS) and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) score. The primary outcome was incident all-cause dementia, Alzheimer disease, vascular dementia, and non-vascular dementia extracted from hospital and primary care records using ICD-10 codes. Censored Cox proportional hazards models were used to estimate the risk of developing dementia and reported as hazard ratios (HRs) with their 95% confidence interval (CI). Analyses were adjusted for age, sex, education and various lifestyle and health-related factors. RESULTS:The analysis included 121 521 participants (mean age: 55.7 years; 53.5% women), followed for a median of 10.9 years. During follow-up, 621 participants developed dementia. Compared with individuals with the lowest dietary adherence (Quartile 1), those in the highest adherence group (Quartile 4) showed a lower risk of all-cause dementia for MDS (HR: 0.53; 95% CI: 0.45-0.63), MIND (HR: 0.61; 95% CI: 0.48-0.78), and RFS (HR: 0.66; 95% CI: 0.53-0.85). Similar associations were observed for Alzheimer disease and MDS (HR: 0.55; 95% CI: 0.46-0.67), RFS (HR: 0.61; 95% CI: 0.47-0.80), and MIND (HR: 0.66; 95% CI: 0.51-0.87). For vascular dementia, only MDS (HR: 0.46; 95% CI: 0.31-0.68) and MIND (HR: 0.68; 95% CI: 0.40-0.97) showed a lower risk. These associations remained in a 5-year landmark analysis. No associations were observed for HDI with any dementia outcome. Our findings indicate that higher adherence to specific dietary patterns, particularly the Mediterranean, RFS and MIND diet, is associated with a lower risk of dementia. CONCLUSIONS:The Mediterranean Diet demonstrated the strongest association. These results highlight the potential of healthy dietary patterns to improve brain health in older adults.