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BackgroundAutopsy studies of former contact sports athletes, including soccer and rugby players, frequently report chronic traumatic encephalopathy, a neurodegenerative pathology associated with traumatic brain injury. Nevertheless, little is known about the risk of neurodegenerative disease in these populations. We hypothesised that neurodegenerative disease risk would be higher among former elite rugby union players than the general population.MethodsWe conducted a retrospective cohort study accessing national electronic records on death certification, hospital admissions and dispensed prescriptions for a cohort of 412 male Scottish former international rugby union players and 1236 members of the general population, matched to former players by age, sex and area socioeconomic status. Mortality and incident neurodegenerative disease diagnoses among former rugby players were then compared with the matched comparison group.ResultsOver a median 32 years follow-up from study entry at age 30 years, 121 (29.4%) former rugby players and 381 (30.8%) of the matched comparison group died. All-cause mortality was lower among former rugby players until 70 years of age with no difference thereafter. During follow-up, 47 (11.4%) former rugby players and 67 (5.4%) of the comparison group were diagnosed with incident neurodegenerative disease (HR 2.67, 95% CI 1.67 to 4.27, pConclusionsThis study adds to our understanding of the association between contact sports participation and the risk of neurodegenerative disease. While further research exploring this interaction is required, in the meantime strategies to reduce exposure to head impacts and head injuries in sport should be promoted.

Multiple studies have identified birth outside regular working hours as an independent risk factor for neonatal death. An increased incidence of birth asphyxia has been implicated as the most likely causal mechanism. Although birth asphyxia can cause adverse neurodevelopmental and educational outcomes among survivors, long term implications of birth outside regular working hours are unknown. In a large national cohort of singleton births in Scotland, we studied whether birth during the evening/night or weekend was independently associated with additional support need (ASN) at school age.

Summary Background Internationally, smoking prevalence among people in prison custody (ie, people on remand awaiting trial, awaiting sentencing, or serving a custodial sentence) is high. In Scotland, all prisons implemented a comprehensive smoke-free policy in 2018 after a 16-month anticipatory period. In this study, we aimed to use data on medication dispensing to assess the impact of this policy on cessation support, health outcomes, and potential unintended consequences among people in prison custody. Methods We did an interrupted time-series analysis using dispensing data for 44 660 individuals incarcerated in 14 closed prisons in Scotland between March 30, 2014, and Nov 30, 2019. We estimated changes in dispensing rates associated with the policy announcement (July 17, 2017) and full implementation (Nov 30, 2018) using seasonal autoregressive integrated moving average models. Medication categories of primary interest were treatments for nicotine dependence (as an indicator of smoking cessation or abstinence attempts), acute smoking-associated illnesses, and mental health (antidepressants). We included antiepileptic medications as a negative control. Findings A 44% step increase in dispensing of treatments for nicotine dependence was observed at implementation (2250 items per 1000 people in custody per fortnight, 95% CI 1875 to 2624) due primarily to a 42% increase in dispensing of nicotine replacement therapy (2109 items per 1000 people in custody per fortnight, 1701 to 2516). A 9% step decrease in dispensing for smoking-related illnesses was observed at implementation, largely accounted for by respiratory medications (−646 items per 1000 people in custody per fortnight, −1111 to −181). No changes associated with announcement or implementation were observed for mental health dispensing or antiepileptic medications (control). Interpretation Smoke-free prison policies might improve respiratory health among people in custody and encourage smoking abstinence or cessation without apparent short-term adverse effects on mental health dispensing. Funding National Institute of Health Research Public Health Research programme, Scottish Government Chief Scientist Office, and UK Medical Research Council.

ObjectivesThe risk of suicide among UK military veterans remains unclear. Few recent studies have been undertaken, and most studies found no clear evidence of increased risk. We used data from the Trends in Scottish Veterans Health cohort to investigate suicides up to 2017 in order to examine whether there have been any changes in the long-term pattern of veteran suicides since our earlier study to 2012, and to compare trends in the risk of suicide among veterans with matched non-veterans.MethodRetrospective cohort study of 78 000 veterans and 253 000 non-veterans born between 1945 and 1995, matched for age, sex and area of residence, using survival analysis to examine the risk of suicide in veterans in comparison with non-veterans overall and by subgroup, and to investigate associations with specific mental health conditions.ResultsUp to 37 years of follow-up, 388 (0.5%) veterans and 1531 (0.6%) non-veterans died from suicide. The risk of suicide among veterans did not differ from non-veterans overall. Increased risk among early service leavers was explained by differences in deprivation, and the previously reported increased risk in female veterans is now confined to older women. Suicide was most common in the fifth decade of life, and around 20 years postservice. A history of mood disorder or post-traumatic stress disorder was non-significantly more common in veterans.ConclusionsVeterans are not at increased risk of suicide overall. The highest risk for both men and women is in middle age, many years after leaving service.

Objective: Transition from school to early adulthood incurs many changes and may be associated with deterioration in general health in youth with autism. We aimed to investigate this.Method: The National Longitudinal Transitions Study-2 is a USA nationally representative sample of youth receiving special education services, aged 13–17 at wave 1, followed-up over 10 years in five data collection waves. We conducted random-effects ordered logistic regressions to determine the odds ratios (OR) with 95% confidence intervals of wave, age, sex, ethnicity/race, additional intellectual disabilities, parental/guardian relationship status, and household income being associated with general health status in youth with autism.Results: Across waves, only between 74.3%–69.6% had excellent/very good health (71.7%–58.8% in those with co-occurring intellectual disabilities), but wave was not associated with health status. Associations were with age OR = 1.18 (1.04, 1.33), co-occurring intellectual disabilities OR = 1.56 (1.00, 2.44), and household income OR = 0.61 (0.40, 0.94) at $30,001–$50,000, OR = 0.44 (0.27, 0.72) at $50,001–$70,000, and OR = 0.34 (0.20, 0.56) at $70,001+. Sex, ethnicity/race, and parental/guardian relationship status were not associated with health status.Conclusion: There was little change in general health status longitudinally across the transitional period, but the proportion with excellent/very good health was low at each wave. Transitional planning should consider co-occurring intellectual disabilities, and the wider socioeconomic context in which children/youth with autism are raised. Lack of other longitudinal studies indicates a need for replication.

Supplemental Digital Content is available in the text., Background: Abdominal aortic aneurysm (AAA) can occur in patients who are ineligible for routine ultrasound screening. A simple AAA risk score was derived and compared with current guidelines used for ultrasound screening of AAA. Methods: United Kingdom Biobank participants without previous AAA were split into a derivation cohort (n=401 820, 54.6% women, mean age 56.4 years, 95.5% White race) and validation cohort (n=83 816). Incident AAA was defined as first hospital inpatient diagnosis of AAA, death from AAA, or an AAA-related surgical procedure. A multivariable Cox model was developed in the derivation cohort into an AAA risk score that did not require blood biomarkers. To illustrate the sensitivity and specificity of the risk score for AAA, a theoretical threshold to refer patients for ultrasound at 0.25% 10-year risk was modeled. Discrimination of the risk score was compared with a model of US Preventive Services Task Force (USPSTF) AAA screening guidelines. Results: In the derivation cohort, there were 1570 (0.40%) cases of AAA over a median 11.3 years of follow-up. Components of the AAA risk score were age (stratified by smoking status), weight (stratified by smoking status), antihypertensive and cholesterol-lowering medication use, height, diastolic blood pressure, baseline cardiovascular disease, and diabetes. In the validation cohort, over 10 years of follow-up, the C-index for the model of the USPSTF guidelines was 0.705 (95% CI, 0.678–0.733). The C-index of the risk score as a continuous variable was 0.856 (95% CI, 0.837–0.878). In the validation cohort, the USPSTF model yielded sensitivity 63.9% and specificity 71.3%. At the 0.25% 10-year risk threshold, the risk score yielded sensitivity 82.1% and specificity 70.7% while also improving the net reclassification index compared with the USPSTF model +0.176 (95% CI, 0.120–0.232). A combined model, whereby risk scoring was combined with the USPSTF model, also improved prediction compared with USPSTF alone (net reclassification index +0.101 [95% CI, 0.055–0.147]). Conclusions: In an asymptomatic general population, a risk score based on patient age, height, weight, and medical history may improve identification of asymptomatic patients at risk for clinical events from AAA. Further development and validation of risk scores to detect asymptomatic AAA are needed.

BackgroundFew studies have examined whether UK military veterans are at an increased risk of dementia. We explored the risk of dementia in Scottish military veterans aged up to 73 years in comparison with people who have never served.MethodsRetrospective cohort study of 78 000 veterans and 253 000 people with no record of service, matched for age, sex and area of residence, with up to 37 years follow-up, using Cox proportional hazard analysis to compare risk of dementia in veterans and non-veterans, overall and by subgroup.ResultsDementia was recorded in 0.2% of both veterans and non-veterans overall, Cox proportional hazard ratio 0.98, 95% confidence interval (CI) 0.82–1.19, p = 0.879 (landmark age: 50 years), with no difference for men but increased risk in veteran women and Early Service Leavers. Post-traumatic stress disorder (PTSD) was associated with a higher risk of dementia in both veterans and non-veterans, although possibly to a lesser degree in veterans. A history of mood disorder was strongly associated with developing dementia, greater in veterans than in non-veterans, odds ratio 1.54, 95% CI 1.01–2.35, p = 0.045.ConclusionsThere was no evidence to suggest that military service increased the risk of dementia, although this may change as the cohort ages. The well-documented association with PTSD shows no evidence of being stronger in veterans; by contrast, the association of mood disorder with dementia is much stronger in veterans. Healthcare providers should carefully assess the cognitive status of older veterans presenting with depressive illness in order to identify early dementia and ensure optimum management.

Background and aims On 1 May 2018, Scotland became the first country in the world to introduce minimum unit pricing (MUP), a strength-based floor price below which alcohol cannot be sold, across all alcoholic beverages. The legislation contains a sunset clause meaning a comprehensive mixed-methods evaluation of its impact across a range of outcomes will inform whether it will continue beyond its sixth year. In this study, we assessed the impact of MUP on off-trade alcohol sales (as a proxy for consumption) after its first year. Design, setting and participants Controlled interrupted time-series regression was used to assess the impact of MUP on alcohol sales among off-trade retailers in Scotland in the year after it was introduced, with England and Wales (EW) being the control group. In adjusted analyses, we included household disposable income, on-trade alcohol sales and substitution between beverage categories as covariates. Measurements Weekly data on the volume of pure alcohol sold by off-trade retailers in Scotland and EW between January 2013 and May 2019, expressed as litres of pure alcohol per adult. Findings The introduction of MUP in Scotland was associated with a 3.5% [95% confidence interval (CI) = 2.2-4.9%] reduction in off-trade alcohol sales per adult after adjustment for the best available geographical control, disposable income and substitution. In unadjusted analysis, the introduction of MUP was associated with a 2.0% (95% CI = 0.4-3.6%) reduction in off-trade alcohol sales per adult in Scotland. In EW, there was a 2.4% (95% CI = 0.8-4.0%) increase during the same time-period. The reduction in off-trade alcohol sales in Scotland was driven by reduced sales of spirits, cider and perry beverage categories. Conclusion The implementation of minimum unit pricing for alcohol in Scotland in 2018 appears to have been associated with a reduction in off-trade alcohol sales after its first year.

Background Traumatic brain injury (TBI) is a leading cause of death and disability among young children and adolescents and the effects can be lifelong and wide-reaching. Although there have been numerous studies to evaluate the impact of childhood head injury on educational outcomes, few large-scale studies have been conducted, and previous research has been limited by issues of attrition, methodological inconsistencies, and selection bias. We aim to compare the educational and employment outcomes of Scottish schoolchildren previously hospitalised for TBI with their peers. Methods and findings A retrospective, record-linkage population cohort study was conducted using linkage of health and education administrative records. The cohort comprised all 766,244 singleton children born in Scotland and aged between 4 and 18 years who attended Scottish schools at some point between 2009 and 2013. Outcomes included special educational need (SEN), examination attainment, school absence and exclusion, and unemployment. The mean length of follow up from first head injury varied by outcome measure; 9.44 years for assessment of SEN and 9.53, 12.70, and 13.74 years for absenteeism and exclusion, attainment, and unemployment, respectively. Logistic regression models and generalised estimating equation (GEE) models were run unadjusted and then adjusted for sociodemographic and maternity confounders. Of the 766,244 children in the cohort, 4,788 (0.6%) had a history of hospitalisation for TBI. The mean age at first head injury admission was 3.73 years (median = 1.77 years). Following adjustment for potential confounders, previous TBI was associated with SEN (OR 1.28, CI 1.18 to 1.39, p < 0.001), absenteeism (IRR 1.09, CI 1.06 to 1.12, p < 0.001), exclusion (IRR 1.33, CI 1.15 to 1.55, p < 0.001), and low attainment (OR 1.30, CI 1.11 to 1.51, p < 0.001). The average age on leaving school was 17.14 (median = 17.37) years among children with a TBI and 17.19 (median = 17.43) among peers. Among children previously admitted for a TBI, 336 (12.2%) left school before age 16 years compared with 21,941 (10.2%) of those not admitted for TBI. There was no significant association with unemployment 6 months after leaving school (OR 1.03, CI 0.92 to 1.16, p = 0.61). Excluding hospitalisations coded as concussion strengthened the associations. We were not able to investigate age at injury for all outcomes. For TBI occurring before school age, it was impossible to be certain that SEN had not predated the TBI. Therefore, potential reverse causation was a limitation for this outcome. Conclusions Childhood TBI, sufficiently severe to warrant hospitalisation, was associated with a range of adverse educational outcomes. These findings reinforce the importance of preventing TBI where possible. Where not possible, children with a history of TBI should be supported to minimise the adverse impacts on their education.

Background Stigmatized behaviours are often underreported, especially in pregnancy, making them challenging to address. The Alcohol and Child Development Study (ACDS) seeks to inform prevention of foetal alcohol harm, linking self-report as well as a maternal blood alcohol biomarker with child developmental outcomes. Samples were requested using passive, generic consent. The success of this approach at minimizing bias is presented comparing characteristics of women who provided samples to those who did not. Methods All pregnant women in the study city were sent a Patient Information Sheet (PIS) with their first NHS obstetric appointment letter. The PIS informed them that the NHS would like to take an extra blood sample for research purposes, unless they opted out. Neither the women nor the midwives were informed that the samples might be tested for an alcohol biomarker. This paper examines the extent to which women who provided the extra sample were representative of women where no sample was provided, in terms of routinely collected information: age; body mass index; area-based deprivation; previous pregnancies, abortions and caesarians; smoking status and carbon monoxide level; self-reported alcohol use, gestation and birth weight of their baby. Chi-square and Mann-Whitney U tests were used to compare groups. Results 3436 (85%) of the 4049 pregnant women who attended their appointment provided the extra sample. Women who did not were significantly younger (p p p Conclusions The use of passive consent without disclosure of the specific research focus resulted in a high level of sample provision. There was no evidence that study blinding was breached, and women who provided a sample were more likely to report alcohol consumption. Passive consent to draw additional blood for research purposes at routine antenatal venipuncture reduced sampling bias compared to asking women to give blood for an alcohol study. This methodology may be useful for other stigmatised behaviours.

Background This study aimed to study the association between shift work and incident and fatal cardiovascular disease (CVD), and to explore modifying and mediating factors. Methods This is a population-based, prospective cohort study with a median follow-up of 11 years; 238 661 UK Biobank participants who were in paid employment or self-employed at baseline assessment were included. Results Shift workers had higher risk of incident [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.06–1.19] and fatal (HR 1.25, 95% CI 1.08–1.44) CVD compared with non-shift workers, after adjusting for socio-economic and work-related factors. The risk was higher with longer duration of shift work, in women and in jobs with little heavy manual labour. Current smoking, short sleep duration, poor sleep quality, adiposity, higher glycated haemoglobin and higher cystatin C were identified as the main potentially modifiable mediators. Mediators collectively explained 52.3% of the associations between shift work and incident CVDs. Conclusions Shift workers have higher risk of incident and fatal CVD, partly mediated through modifiable risk factors such as smoking, sleep duration and quality, adiposity and metabolic status. Workplace interventions targeting these mediators have the potential to alleviate shift workers’ CVD risk.

Background Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in-utero exposure to antihypertensive treatment is conflicting with many studies suffering from significant methodological issues. Method We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010-2014 in Scotland to assess outcomes following in-utero exposure to antihypertensive medication. Results We identified a cohort of 265 488 eligible mother-child pairs born over the study period; of which, 2433 were exposed in utero to antihypertensive medication, 4391 exposed to treated late-onset hypertension and 6066 exposed to untreated hypertension during pregnancy. In-utero antihypertensive exposure was associated with an increased risk of circulatory defects (aOR 2.29; 99% CI 1.14-4.59) compared with normal controls and the untreated hypertensive group. We report no increased odds of any developmental outcomes at 2.5 years of age following exposure to antihypertensive medication during pregnancy, untreated hypertension or late-onset hypertension. Conclusion Although circulatory defects may be associated with antihypertensive medication exposure during pregnancy, the mechanisms underlying this process are unclear.

Introduction\ud It is unclear what combinations of physical capability markers used to define sarcopenia have the strongest associations with health outcomes.\ud \ud Aim\ud To compare the associations between different combinations of physical capability markers of sarcopenia with cardiovascular and respiratory outcomes and all-cause mortality.\ud \ud Study design\ud 469,830 UK Biobank participants were included in this prospective study. Four groups were derived based on combinations of three physical capability markers used to define sarcopenia or severe sarcopenia: gait speed, grip strength and muscle mass. Outcomes studied were all-cause mortality, as well as incidence and mortality from cardiovascular disease (CVD), respiratory disease and chronic obstructive pulmonary disease (COPD).\ud \ud Results\ud All combinations of physical capability markers used to define sarcopenia or severe sarcopenia identified individuals at increased risk of respiratory disease and all-cause mortality. However, the definition most strongly associated with a wide range of adverse health outcomes was the combination of slow gait speed plus low muscle mass, followed by severe sarcopenia, and the combination of slow gait speed plus low grip strength. The current definition of sarcopenia (low grip strength plus low muscle mass) had the weakest associations with all-cause (HR: 1.35 [95% CI: 1.07 to 1.71]) and respiratory mortality (HR: 1.88 [95% CI: 1.15 to 3.10]), as well as respiratory disease (HR: 1.38 [95% CI: 1.11 to 1.73]) and COPD incidence (HR: 2.08 [95% CI: 1.14 to 3.79]).\ud \ud Conclusions\ud Associations of sarcopenia with adverse outcomes were strongest when sarcopenia was defined as slow gait speed plus low muscle mass, followed by severe sarcopenia, suggesting that this combination of physical capability markers should be still considered in the diagnosis of sarcopenia.

Background In sub-Saharan Africa, burn and scald injuries occur more commonly in children aged less than five years, than in any other age group, and carry a high lifetime morbidity. The optimal first aid at the time of injury includes the use of cool running water, which can reduce pain, scarring, and skin grafting. Data on the types of first aid used in Malawi is lacking, as is an in-depth understanding of the underlying factors which may influence this health behaviour. This study sought to: (a) document the types of first aid after paediatric burn and scald injuries in Southern Malawi; and (b) explore factors affecting the choice of first aid used. Methods andfindings We conducted a sequential explanatory mixed methods study. Quantitative analysis of a prospectively collected database of all patients aged less than 17 years admitted to the only burn unit in Southern Malawi was followed by thematic analysis of semi-structured interviews with 15 adults who had witnessed a paediatric burn or scald injury. 1326 patients aged less than 17 years were admitted to the Queen Elizabeth Central Hospital between July 2009 and December 2016. Median age was 3.0 years (IQR 1.9–5.0) and male to female ratio 1:0.9. The commonest cause of injury was hot liquid (45%), followed by open fire (31%) and porridge (12%). First aid was applied in 829 patients (69%), the commonest applications used were water (31%) and egg (21%). There was a statistically significant association between the type of first aid and secondary education of the father (p = 0.009) or mother (p = 0.036); however, the type of first aid used was more likely to be egg rather than water. Analysis of qualitative interviews identified four main themes: perceived roles and responsibilities within the community, drivers of individual behaviours, availability, and trust. Participants reported using eggs as a first aid treatment, as these were readily available and were seen to reduce the occurrence of blisters and prevent peeling of the skin. By comparison, there was a strong underlying fear of using water on burn injuries due to its association with peeling of the skin. Intergenerational learning appeared to play a strong role in influencing what is used at the time of injury, and mothers were the key source of this information. Conclusions This study provides the largest description of first aid use in sub-Saharan Africa, strengthening the evidence that remedies aside from water are commonly used and that higher parental education levels do not translate to increased use of water, but rather use of alternative treatments. Our qualitative findings allow improved understanding of how first aid for paediatric burns is perceived in rural Malawi communities, providing insight as to why certain first aid choices are made and the possible barriers and facilitators to the adoption of water as a first aid treatment.

Hypertensive disorders during pregnancy are an important risk to mother and fetus, frequently necessitating antihypertensive treatment. Data describing the safety of in utero exposure to antihypertensive treatment is conflicting, with many studies suffering from significant methodological issues, such as inappropriate study design, small sample sizes, and no untreated control group. We conducted a retrospective cohort study using linked routinely collected healthcare records for 268 711 children born 2010–2014 in Scotland to assess outcomes following in utero exposure to antihypertensive medication. We identified a cohort of 265 488 eligible children born over the study period; of which, 2350 were exposed to in utero antihypertensive medication, 4391 exposed to treated late-onset hypertension, and 7971 exposed to untreated hypertension during pregnancy. Untreated hypertension was associated with increased risk of preterm birth (adjusted risk ratio [aRR], 1.15 [99% CI, 1.01–1.30]), low birth weight (aRR, 2.01 [99% CI, 1.72–2.36]) and being small for gestational age (aRR, 1.50 [99% CI, 1.35–1.66]), while in utero antihypertensive exposure was also associated with preterm birth (aRR, 3.12 [99% CI, 2.68–3.64]), low birth weight (aRR, 2.23 [99% CI, 1.79–2.78]), and being small for gestational age (aRR, 2.13 [99% CI, 1.81–2.52]). Late-onset hypertension was also associated with preterm birth (aRR, 2.21 [99% CI, 1.86–2.62]), low birth weight (aRR, 2.06 [99% CI, 1.74–2.43]), and being small for gestational age (aRR, 1.90 [99% CI, 1.68–2.16]). Our results suggest that hypertension is a key risk factor for low birth weight and preterm birth. Although preterm birth may be associated with antihypertensive medication exposure during pregnancy, these associations may reflect increasing hypertension severity necessitating treatment.

Funding Health Data Research UK (grant reference number MR/S003800/1). Acknowledgements The study was sponsored by Health Data Research UK (www.hdruk.ac.uk), which is a joint investment led by the Medical Research Council, together with the National Institute for Health Research (England), the Chief Scientist Office (Scotland), Health and Care Research Wales, Health and Social Care Research and Development Division (Public Health Agency, Northern Ireland), the Engineering and Physical Sciences Research Council, the Economic and Social Research Council, the British Heart Foundation and Wellcome (grant reference number MR/S003800/1). The sponsor and funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication. This study formed part of a wider PhD thesis undertaken by the lead author within the University of Glasgow and was published in 2017. Certain sections of this paper appear in the thesis, which is accessible and downloadable from the following link: http://theses.gla.ac.uk/8594/1/2017flemingphd.pdf. Author Contributions J.P.P. had the original concept. All authors agreed the study design. D.C. and A.K. provided data and undertook record linkage. M.F. and D.F.M. undertook the statistical analyses. All authors interpreted the results. M.F. and J.P.P. drafted the manuscript and all other authors contributed revisions. All authors reviewed and approved the final version of the manuscript. M.F. is guarantor for the study. Approvals The authors applied for permission to access, link and analyse these data and undertook mandatory training in data protection, IT security and information governance. Therefore, the datasets generated and analysed during the study are not publicly available. The study was approved by the National Health Service Privacy Advisory Committee and covered by a data-processing agreement between Glasgow University and ISD, and a data-sharing agreement between Glasgow University and ScotXed. All data were linked by the Electronic Data Research and Innovation Service (eDRIS), part of NHS National Services Scotland. Ethics The NHS West of Scotland Research Ethics Service confirmed that formal NHS ethics approval was not required, since the study involved anonymized extracts of routinely collected data with an acceptably negligible risk of identification. Conflict of interest: None declared

Key Points Question What is the association of field position, career length, and playing era with risk of neurodegenerative disease in male former professional soccer players? Findings In this cohort study of 7676 Scottish male former professional soccer players and 23 028 general population control individuals matched by sex, year of birth, and area socioeconomic status, risk of neurodegenerative disease among former soccer players varied by field position and career length but was similar across era of participation. Meaning In this study, risk of neurodegenerative disease was higher among former professional soccer players with longer careers and among those in nongoalkeeper positions, indicating that factors associated with nongoalkeeper positions should be scrutinized to mitigate risk; meanwhile, strategies to reduce head impact exposure may be advisable to reduce negative outcomes in this population., This cohort study investigates the association of field position, professional career length, and playing era with risk of neurodegenerative disease among Scottish male former professional soccer players., Importance Neurodegenerative disease mortality is higher among former professional soccer players than general population controls. However, the factors contributing to increased neurodegenerative disease mortality in this population remain uncertain. Objective To investigate the association of field position, professional career length, and playing era with risk of neurodegenerative disease among male former professional soccer players. Design, Setting, and Participants This cohort study used population-based health record linkage in Scotland to evaluate risk among 7676 male former professional soccer players born between January 1, 1900, and January 1, 1977, and 23 028 general population control individuals matched by year of birth, sex, and area socioeconomic status providing 1 812 722 person-years of follow-up. Scottish Morbidity Record and death certification data were available from January 1, 1981, to December 31, 2016, and prescribing data were available from January 1, 2009, to December 31, 2016. Database interrogation was performed on December 10, 2018, and data were analyzed between April 2020 and May 2021. Exposures Participation in men’s soccer at a professional level. Main Outcomes and Measures Outcomes were obtained by individual-level record linkage to national electronic records of mental health and general hospital inpatient and day-case admissions as well as prescribing information and death certification. Risk of neurodegenerative disease was evaluated between former professional soccer players and matched general population control individuals. Results In this cohort study of 30 704 male individuals, 386 of 7676 former soccer players (5.0%) and 366 of 23 028 matched population control individuals (1.6%) were identified with a neurodegenerative disease diagnosis (hazard ratio [HR], 3.66; 95% CI, 2.88-4.65; P

Background:\ud \ud Venous thromboembolism (VTE) is a common, life-threatening complication of COVID-19 infection. COVID-19 risk-prediction models include a history of venous thromboembolism. However, it is unclear whether remote history (>9 years previously) of VTE also confers increased risk of COVID-19.\ud \ud Objectives:\ud \ud To investigate possible association between VTE and COVID-19 severity, independent of other risk factors.\ud \ud Methods:\ud \ud Cohort study of UK Biobank participants recruited between 2006-2010. Baseline data, including history of VTE, were linked to COVID-19 test results, COVID-19 related hospital admissions and COVID-19 deaths. The risk of COVID-19 hospitalisation or death was compared for participants with a remote history VTE versus without. Poisson regression models were run univariately then adjusted stepwise for socio-demographic, lifestyle and comorbid covariates.\ud \ud Results:\ud \ud After adjustment for socio-demographic and lifestyle confounders and comorbid conditions, remote history of VTE was associated with non-fatal community (RR 1.61, 95% CI 1.02-2.54, p=0.039), non-fatal hospitalised (RR 1.52, 95% CI 1.06-2.17, p=0.024) and severe (hospitalised or fatal) (RR 1.40, 95% CI 1.04-1.89, p=0.025) COVID-19. Associations with remote history of VTE were stronger among men (severe COVID-19: RR 1.68, 95% CI 1.14-2.42, p=0.009) than for women (severe COVID-19: RR 1.07, 95% CI 0.66-1.74, p=0.786).\ud \ud Conclusion:\ud \ud Our findings support inclusion of remote history of VTE in COVID-19 risk-prediction scores, and consideration of sex-specific risk scores.

ObjectivesTo examine the risk of cardiovascular disease (CVD) in Scottish military veterans in comparison with people who had never served in long-term follow-up to 2017, and to compare the findings with our earlier study to 2012 to assess trends.DesignRetrospective cohort study with up to 37 years follow-up.SettingPseudo-anonymised extract of computerised Scottish National Health Service records and national vital records.Participants78 000 veterans and 253 000 people with no record of service matched for age, sex and area of residence.Outcome measuresRisk of first occurrence of acute myocardial infarction, peripheral arterial disease and stroke in veterans compared with non-veterans, overall and by sex and birth cohort.ResultsA first episode of CVD was recorded in 5.7% of veterans and 4.8% of non-veterans overall, Cox proportional HR 1.16, 95% CIs 1.12 to 1.20, p=0.001. The difference was only significant for men, and for veterans born before 1960, and was highest in veterans with the shortest service. In all categories, the difference in risk was less than at the end of 2012.ConclusionsThe excess burden of CVD in veterans which was evident at the end of 2012 has reduced in the following 5 years from 23% to 16% overall. The increased risk continues to affect only those veterans born prior to 1960, suggesting that improvements in military health promotion since 1978, when veterans born from 1960 joined the armed forces, have had an important and ongoing beneficial effect on the long-term health of veterans.

Background Risk of preeclampsia varies by month of delivery. We tested whether this seasonal patterning may be mediated through maternal vitamin D concentration using antenatal exposure to UV‐B radiation as an instrumental variable. Methods and Results Scottish maternity records were linked to antenatal UV‐B exposure derived from satellites between 2000 and 2010. Logistic regression analyses were used to explore the association between UV‐B and preeclampsia, adjusting for the potential confounding effects of month of conception, child's sex, gestation, parity, and mean monthly temperature. Of the 522 896 eligible singleton deliveries, 8689 (1.66%) mothers developed preeclampsia. Total antenatal UV‐B exposure ranged from 43.18 to 101.11 kJ/m 2 and was associated with reduced risk of preeclampsia with evidence of a dose‐response relationship (highest quintile of exposure: adjusted odds ratio, 0.57; 95% CI, 0.44–0.72; P Conclusions The seasonal patterning of preeclampsia may be mediated through low maternal vitamin D concentration in winter resulting from low UV‐B radiation. Interventional studies are required to determine whether vitamin D supplements or UV‐B–emitting light boxes can reduce the seasonal patterning of preeclampsia.

Objective The aim of this study is to systematically review published studies, reporting outcomes to offspring following in utero exposure to antidepressant medications, which used an untreated depressed comparison group. Methods OVID, Scopus, EBSCO Collections, the Cochrane Library and Web of Science databases were searched for relevant publications published between January 1950 and May 2018 and a total of 188 potentially eligible studies were identified. Results Following review, 16 primary studies were eligible for inclusion. Antidepressant exposure was associated with an increased risk of lower gestational age, preterm birth, but not low birthweight or being small for gestational age compared to untreated depression. There is some evidence that congenital defects are associated with antidepressant use, particularly between cardiac defects and paroxetine use. There is conflicting evidence regarding neurodevelopment in offspring, with some reports of increased incidence of autistic spectrum disorders and depression, but also reports of no problems when measuring emotional symptoms, peer problems, conduct problems and hyperactivity-inattention scores. Conclusion When compared with an untreated depressed group, antidepressant exposure was associated with adverse outcomes at birth, while there is insufficient data to determine whether the association between antidepressants and congenital defects or developmental disorders is a true association. However, although we compared treated vs. untreated depression there still may be residual confounding as an untreated depressed group is likely to have less severe depression.

Objective To investigate the associations of objectively measured cardiorespiratory fitness (CRF) and grip strength (GS) with incident heart failure (HF), a clinical syndrome that results in substantial social and economic burden, using UK Biobank data. Patients and Methods Of the 502,628 participants recruited into the UK Biobank between April 1, 2007, and December 31, 2010, a total of 374,493 were included in our GS analysis and 57,053 were included in CRF analysis. Associations between CRF and GS and incident HF were investigated using Cox proportional hazard models, with adjustment for known measured confounders. Results During a mean of 4.1 (range, 2.4-7.1) years, 631 HF events occurred in those with GS data, and 66 HF events occurred in those with CRF data. Higher CRF was associated with 18% lower risk for HF (hazard ratio [HR], 0.82; 95% CI, 0.76-0.88) per 1–metabolic equivalent increment increase and GS was associated with 19% lower incidence of HF risk (HR, 0.81; 95% CI, 0.77-0.86) per 5-kg increment increase. When CRF and GS were standardized, the HR for CRF was 0.50 per 1-SD increment (95% CI, 0.38-0.65), and for GS was 0.65 per 1-SD increment (95% CI, 0.58-0.72). Conclusion Our data indicate that objective measurements of physical function (GS and CRF) are strongly and independently associated with lower HF incidence. Future studies targeting improving CRF and muscle strength should include HF as an outcome to assess whether these results are causal.

Background higher grip strength is associated with better health outcomes. The optimal way to report grip strength (i.e. absolute vs. relative) for prediction, however, remains to be established. Methods in participants (aged 37–73 at baseline) from the UK Biobank, we examined the associations of grip strength, expressed in absolute terms (kilograms) and relative to anthropometric variables, with mortality and disease incidence, after exclusion of the first 2 years of follow-up, and compared risk predictions scores of handgrip strength when differentially expressed. Results of the 356 721 participants included in the analysis 6,234 died (1.7%) and 4,523 developed CVD (1.3%) over a mean follow-up of 5.0 years (ranging from 3.3 to 7.8) for mortality and 4.1 years (ranging from 2.4 to 7.0) for disease incidence data. As expected, baseline higher grip strength was associated with lower risk of all-cause and cause specific mortality and incidence. These associations did not meaningfully differ when grip-strength was expressed in absolute terms, vs. relative to height, weight, fat-free mass, BMI, fat-free mass index and fat-free mass, or as z-scores. Similarly the different ways of expressing grip strength had little effect on the ability of grip strength to improve risk prediction, based on C-index change, of an office-based risk score. Conclusions the ability of grip strength to predict mortality is not altered by changing how it is expressed.

Background Driving is a common type of sedentary behaviour; an independent risk factor for poor health. The study explores whether driving is also associated with other unhealthy lifestyle factors. Methods In a cross-sectional study of UK Biobank participants, driving time was treated as an ordinal variable and other lifestyle factors dichotomized into low/high risk based on guidelines. The associations were explored using chi-square tests for trend and binary logistic regression. Results Of the 386 493 participants who drove, 153 717 (39.8%) drove Conclusions Sedentary behaviour, such as driving, is known to have an independent association with adverse health outcomes. It may have additional impact mediated through its effect on other aspects of lifestyle. People with long driving times are at higher risk and might benefit from targeted interventions.

Background: Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction. Methods: Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non–HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events). Results: ApoB, LDL-C, and non–HDL-C were highly correlated ( r >0.90), while HDL-C was strongly correlated with ApoA1 ( r =0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non–HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non–HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non–HDL-C did not further improve discrimination. Conclusions: Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C.

Background: \ud Childhood epilepsy can adversely affect education and employment in addition to health. Previous studies are small or highly selective producing conflicting results. This retrospective cohort study aims to compare educational and health outcomes of children receiving antiepileptic medication versus peers.\ud \ud Methods: \ud Record linkage of Scotland-wide databases covering dispensed prescriptions, acute and psychiatric hospitalisations, maternity records, deaths, annual pupil census, school absences/exclusions, special educational needs, school examinations, and (un)employment provided data on 766,244 children attending Scottish schools between 2009 and 2013. Outcomes were adjusted for sociodemographic and maternity confounders and comorbid conditions.\ud \ud Results: \ud Compared with peers, children on antiepileptic medication were more likely to experience school absence (Incidence Rate Ratio [IRR] 1.43, 95% CI: 1.38, 1.48), special educational needs (Odds ratio [OR] 9.60, 95% CI: 9.02, 10.23), achieve the lowest level of attainment (OR 3.43, 95% CI: 2.74, 4.29) be unemployed (OR 1.82, 95% CI: 1.60, 2.07), be admitted to hospital (Hazard Ratio [HR] 3.56, 95% CI: 3.42, 3.70), and die (HR 22.02, 95% CI: 17.00, 28.53). Absenteeism partly explained poorer attainment and higher unemployment. Girls and younger children on antiepileptic medication had higher risk of poor outcomes.\ud \ud Conclusions: \ud Children on antiepileptic medication fare worse than peers across educational and health outcomes. In order to reduce school absenteeism and mitigate its effects, children with epilepsy should receive integrated care from a multidisciplinary team that spans education and healthcare.

ObjectiveTo test for interactions between APOE ε4 genotype and lifestyle factors on worse cognitive abilities in UK Biobank.MethodsUsing UK Biobank cohort data, we tested for interactions between APOE ε4 allele presence, lifestyle factors of alcohol intake, smoking, total physical activity and obesity, and sex, on cognitive tests of reasoning, information processing speed, and executive function (n range = 70,988–324,725 depending on the test). We statistically adjusted for potential confounders of age, sex, deprivation, cardiometabolic conditions, and educational attainment.ResultsThere were significant associations between APOE ε4 and worse cognitive abilities, independent of potential confounders, and between lifestyle risk factors and worse cognitive abilities; however, there were no interactions at multiple correction-adjusted p < 0.05, against our hypotheses.ConclusionsOur results do not provide support for the idea that ε4 genotype increases vulnerability to the negative effects of lifestyle risk factors on cognitive ability, but rather support a primarily outright association between APOE ε4 genotype and worse cognitive ability.

Objective: This study aimed to investigate whether the association between a validated genetic profile risk score for BMI (GPRS‐BMI) (based on 93 single‐nucleotide polymorphisms) and phenotypic obesity (BMI) was modified by the combined categories of physical activity (PA) and sedentary behaviors in a large population‐based study. Methods: This study included cross‐sectional baseline data from 338,216 white European adult men and women aged 37 to 73 years. Interaction effects of GPRS‐BMI with the combined categories of PA and sedentary behaviors on BMI were investigated. Results: There was a significant interaction between GPRS‐BMI and the combined categories of objectively measured PA and total sedentary behavior (P[interaction] = 3.5 × 10−6); among physically inactive and highly sedentary individuals, BMI was higher by 0.60 kg/m2 per 1‐SD increase in GPRS‐obesity (P = 8.9 × 10−50), whereas the relevant BMI difference was 38% lower among physically active individuals and those with low sedentary time (β: 0.37 kg/m2; P = 2.3 × 10−51). A similar pattern was observed for the combined categories of objective PA and TV viewing (inactive/high TV viewing β: 0.60 vs. active/low TV viewing β: 0.40 kg/m2; P[interaction] = 2.9 × 10−6). Conclusions: This study provides evidence that combined categories of PA and sedentary behaviors modify the extent to which genetic predisposition to obesity results in higher BMI.

Walking pace is associated with all-cause and cardiovascular disease (CVD) mortality. Whether this association extends to other health outcomes and whether it is independent of total amount of time walked are currently unknown. Therefore, the aim of this study was to investigate whether usual walking pace is associated with a range of health outcomes.UK Biobank participants (318,185 [54%] women) age 40 to 69 yr were included. Walking pace and total walking time were self-reported. The outcomes comprised: all-cause mortality as well as incidence and mortality from CVD, respiratory disease and cancer. The associations were investigated using Cox proportional hazard models.Over a mean of 5.0 yr [ranging from 3.3 to 7.8], 5890 participants died, 18,568 developed CVD, 5430 respiratory disease and 19,234 cancer. In a fully adjusted model, compared to slow pace walkers, men and women, respectively, with a brisk pace having lower risk of mortality from all-causes (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.69-0.90 and HR, 0.73; 95% CI, 0.62-0.85), CVD (HR, 0.62; 95% CI, 0.50-0.76 and HR, 0.80; 95% CI, 0.73-0.88), respiratory disease (HR, 0.58; 95% CI, 0.43-0.78 and HR, 0.66; 95% CI, 0.57-0.77), chronic obstructive pulmonary disease (HR, 0.26; 95% CI, 0.12-0.56 and HR, 0.28; 95% CI, 0.16-0.49). No associations were found for all-cause cancer, colorectal, and breast cancer. However, brisk walking was associated with a higher risk of prostate cancer.Walking pace is associated with lower risk of a wide range of important health conditions, independently of overall time spent walking.

ObjectiveTo investigate the association of cardiorespiratory fitness with all-cause mortality, and cardiovascular disease (CVD), respiratory disease, chronic obstructive pulmonary disease (COPD) and cancer mortality and incidence.DesignProspective population-based study.SettingUK Biobank.ParticipantsOf the 5 02 628 (5.5% response rate) participants recruited by UK Biobank, we included 73 259 (14.6%) participants with available data in this analysis. Of these, 1374 participants died and 4210 developed circulatory diseases, 1293 respiratory diseases and 4281 cancer, over a median of 5.0 years (IQR 4.3–5.7) follow-up.Main outcome measuresAll-cause mortality and circulatory disease, respiratory disease, COPD and cancer (such as colorectal, lung, breast and prostate) mortality/incidence. Fitness was estimated using a submaximal cycle ergometer test.ResultsThe HR for all-cause mortality for each metabolic equivalent of task (MET) higher fitness was 0.96 (95% CI 0.93 to 0.98). Similar results were observed for incident circulatory disease (HR 0.96 [0.95 to 0.97]), respiratory disease (HR 0.96 [0.94 to 0.98]), COPD (HR 0.90 [0.86 to 0.95) and colorectal cancer (HR 0.96 [0.92 to 1.00]). Nonlinear analysis revealed that a high level of fitness (>10METs) was associated with a greater incidence of atrial fibrillation (HR 1.24 [1.07 to 1.44]) and prostate cancer (HR 1.16 [1.02 to 1.32]) compared with average fitness. All results were adjusted for sociodemographic, lifestyle and dietary factors, body composition, and morbidity at baseline and excluded events in the first 2 years of follow-up.ConclusionsHigher cardiorespiratory fitness was associated with lower risk of premature mortality and incidence of CVD, respiratory disease and colorectal cancer.

Background Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders. Methods and findings Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care. Conclusions Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system., In this record-linkage study in Scotland, Michael Fleming and colleagues compare educational and health outcomes for children who are in the care of their local authority with the outcomes of their peers., Author summary Why was this study done? Looked after children, defined as children placed in the care of their local authority, comprise a vulnerable cohort exhibiting poorer educational and health outcomes compared to peers. Only a few small sample studies have been conducted in the UK, and a recent systematic review reported an urgent need for more population-wide research into the educational outcomes of children placed in social care services. To our knowledge, no previous UK studies have dually investigated educational and health outcomes of looked after children compared to peers using an unselected, nationwide cohort. What did the researchers do and find? We linked together 9 Scotland-wide databases to compare educational and health outcomes of looked after children against peers, adjusting for sociodemographic, maternity, and comorbidity confounders. Looked after children had increased risk of school absenteeism and exclusion; special educational need (SEN); poor academic attainment; unemployment; hospitalisation and mortality; and treatment for epilepsy, attention deficit hyperactivity disorder (ADHD), depression, and neurodevelopmental multimorbidity. Among children in care, those looked after away from home had less absenteeism, less exclusion, less unemployment, and better attainment. What do these findings mean? Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.