Search

Daniel Hsiang-Te Tsai,1,2 J Simon Bell,3 Shahab Abtahi,4 Brenda N Baak,5 Marloes T Bazelier,4 Ruth Brauer,6 Adrienne YL Chan,6– 9 Esther W Chan,9– 12 Haoqian Chen,13 Celine SL Chui,9,14,15 Sharon Cook,16 Stephen Crystal,16 Poonam Gandhi,13 Sirpa Hartikainen,17 Frederick K Ho,18 Shao-Ti Hsu,1 Jenni Ilomäki,3 Ju Hwan Kim,19 Olaf H Klungel,4 Marjaana Koponen,17 Wallis CY Lau,6,8,9 Kui Kai Lau,20,21 Terry YS Lum,22 Hao Luo,22 Kenneth KC Man,6,8,9 Jill P Pell,18 Soko Setoguchi,13,23 Shih-Chieh Shao,1,24 Chin-Yao Shen,1 Ju-Young Shin,19,25,26 Patrick C Souverein,4 Anna-Maija Tolppanen,17 Li Wei,6,9 Ian CK Wong,6,8,9,27 Edward Chia-Cheng Lai1 1School of Pharmacy, Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 2Centre for Neonatal and Paediatric Infection, St George’s University of London, London, UK; 3Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia; 4Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; 5PHARMO Institute for Drug Outcomes Research, Utrecht, the Netherlands; 6Research Department of Practice and Policy, UCL School of Pharmacy, London, UK; 7Groningen Research Institute of Pharmacy, Unit of Pharmacotherapy, ‐Epidemiology and ‐Economics, University of Groningen, Groningen, the Netherlands; 8Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 9Laboratory of Data Discovery for Health (D24H), Hong Kong Science Park, Hong Kong, Special Administrative Region, People’s Republic of China; 10Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 11Department of Pharmacy, the University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China; 12The University of Hong Kong Shenzhen Institute of Research and Innovation, Shenzhen, People’s Republic of China; 13Center for Pharmacoepidemiology and Treatment Science (PETS), Institute for Health, Rutgers University, New Brunswick, NJ, USA; 14School of Nursing, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 15School of Public Health, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 16Center for Health Services Research, Rutgers University, New Brunswick, NJ, USA; 17Kuopio Research Centre of Geriatric Care and School of Pharmacy, University of Eastern Finland, Kuopio, Finland; 18School of Health and Wellbeing, University of Glasgow, Glasgow, UK; 19School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; 20Division of Neurology, Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 21State Key Laboratory of Brain and Cognitive Sciences, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 22Department of Social Work and Social Administration, University of Hong Kong, Hong Kong, Special Administrative Region, People’s Republic of China; 23Department of Medicine, Rutgers Robert Wood Johnson Medical School and Pharmacoepidemiology and Treatments Science, Institute for Health, Rutgers University, New Brunswick, NJ, USA; 24Department of Pharmacy, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 25Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, South Korea; 26Department of Biohealth Regulatory Science, Sungkyunkwan University, Seoul, South Korea; 27Aston Pharmacy School, Aston University, Birmingham, UKCorrespondence: Edward Chia-Cheng Lai, School of Pharmacy and Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Email edward_lai@mail.ncku.edu.twPurpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN).Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives.Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK.Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders.Keywords: meta-data, data repository, Neurological and Mental Health Global Epidemiology Network, NeuroGEN

Abstract Objective To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons Design Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. Results Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively) Conclusion In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel.

AIM: To assess the effect of changing clinical practice on the costs and outcomes of percutaneous coronary intervention (PCI) between 1998 and 2002. SETTING: Two tertiary interventional centres. PATIENTS: Consecutive patients undergoing PCI over a 12-month period between 1998 and 2002. DESIGN: Comparative observational study of costs and 12-month clinical outcomes of consecutive PCI procedures in 1998 (n = 1047) and 2002 (n = 1346). Clinical data were recorded in the Scottish PCI register. Repeat PCI, coronary artery bypass graft and mortality were obtained by record linkage. Costs of equipment were calculated using a computerised bar-code system and standard National Health Service reference costs. RESULTS: Between 1998 and 2002, the use of bare metal stents increased from 44% to 81%, and the use of glycoprotein IIB/IIIA inhibitors increased from 0% to 14% of cases. During this time, a significant reduction was observed in repeat target-vessel PCI (from 8.4% to 5.1%, p = 0.001), any repeat PCI (from 11.7% to 9.2%, p = 0.05) and any repeat revascularisation (from 15.1% to 11.3%, p = 0.009) within 12 months. Significantly higher cost per case in 2002 compared with 1998 (mean (standard deviation) 2311 pounds (1158) v 1785 pounds (907), p<0.001) was mainly due to increased contribution from bed-day costs in 2002 (45.0% (16.3%) v 26.2% (12.6%), p = 0.01) associated with non-elective cases spending significantly longer in hospital (6.22 (4.3) v 4.6 (4.3) days, p = 0.01). CONCLUSIONS: Greater use of stents and glycoprotein IIb/IIIa inhibitors between 1998 and 2002 has been accompanied by a marked reduction in the need for repeat revascularisation. Longer duration of hospital stay for non-elective cases is mainly responsible for increasing costs. Strategies to reduce the length of stay could considerably reduce the costs of PCI. [ABSTRACT FROM AUTHOR]

Women with a previous stillbirth are known to be at increased risk of stillbirth in subsequent pregnancies. However, few studies have addressed the association between other complications of pregnancy and the future risk of stillbirth. Using linkage of national pregnancy and perinatal death registries, the authors performed a retrospective cohort study of 133,163 women having a second birth in Scotland between 1992 and 2001 whose first infant was liveborn. The risk of unexplained stillbirth was increased among women with a previous preterm birth (adjusted hazard ratio (HR) = 2.04, 95% confidence interval (CI): 1.34, 3.11), previous delivery of a small for gestational age (SGA) infant (HR = 2.14, 95% CI: 1.59, 2.87), and previous preeclampsia (HR = 1.68, 95% CI: 1.07, 2.62). The associations were similar after adjustment for maternal age, height, marital and smoking status, and interpregnancy interval. There was a statistically significant positive interaction between previous delivery of a SGA infant and previous preeclampsia (p = 0.01): Women with this combination in their first pregnancy had an approximately fivefold risk of unexplained stillbirth in the second pregnancy (HR = 4.95, 95% CI: 2.63, 9.32). Associations were stronger with SGA unexplained stillbirths. The authors conclude that complicated first births of liveborn infants are associated with an increased risk of unexplained stillbirth in the next pregnancy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. DESIGN: Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. METHODS: All PCIs in Scotland during 1997-2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. RESULTS: Of the 17,417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. CONCLUSION: Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery. [ABSTRACT FROM AUTHOR]

Importance: Elite-level contact sport participation is associated with increased dementia risk, which may be attributable to sport-related traumatic brain injury and repetitive head impact exposure. However, the contribution of wider, potentially modifiable dementia risk factors remains uncertain., Objective: To explore the association of potentially modifiable dementia risk factors with dementia risk among former professional soccer players., Design, Setting, and Participants: This retrospective cohort study used electronic health record linkage to national electronic datasets of general and mental health hospital inpatient and day-case admissions, prescribing information, and death certification in Scotland for male former professional soccer players born between January 1, 1900, and December 31, 1990, who were aged 30 years or older on December 31, 2020, and general population control individuals matched by sex, year of birth, and area socioeconomic status. Database interrogation was performed on November 30, 2021, and data were analyzed between January 16, 2023, and July 8, 2024., Exposures: History of smoking, depression, alcohol-related disorders, diabetes, hypertension, hearing loss, and obesity coded within electronic health records., Main Outcomes and Measures: Prevalence of dementia risk factors and their association with incident dementia diagnoses were evaluated and compared between former soccer players and matched controls., Results: The final cohort consisted of 11 984 male former professional soccer players and 35 952 matched controls. Over a median 21 years (IQR, 7-34 years) of follow-up from study entry at age 30 years or older, providing a total of 1 039 848 years of follow-up, 434 former soccer players (3.62%) and 453 matched population controls (1.26%) were identified with a dementia diagnosis (hazard ratio [HR], 3.02; 95% CI, 2.54-3.58; P < .001). Overall, rates of general health and lifestyle dementia risk factors were similar or lower among former soccer players compared with matched controls (eg, diabetes: 4.26% vs 6.35%). Dementia risk associated with these factors among soccer players was similar to or lower than among controls (eg, hypertension: HR, 4.62 [95% CI, 3.69-5.78] vs 6.96 [95% CI, 5.64-8.59])., Conclusions and Relevance: This cohort study found no evidence that high dementia risk among former professional soccer players was associated with potentially modifiable general health and lifestyle dementia risk factors. These data support continuation of measures directed toward reducing exposure to repetitive head impacts and traumatic brain injury in sport.

Background: Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population., Methods: This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37-73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis. Subgroup analyses by age, sex, BMI categories and pre-existing cardiovascular disease were conducted. Mediation analyses using the g-formula were performed to quantify to which extent bone mineral density (BMD) may mediate the association between serum lipids and fracture risk., Results: Over a median follow-up period of 13.8 years, 25 918 (6.8%) of the 383 530 participants without prior fracture had incident fracture cases, and 7591 (4.1%) of the 184 919 participants with primary care data and without baseline osteoporosis were diagnosed with osteoporosis. TG had nonlinear associations with fractures and osteoporosis, whereas Apo B, TC and LDL-C had linear associations. There were also nonlinear associations of Apo A and HDL-C with fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [95% CI 1.10, 1.21]; osteoporosis: HR 1.13 [1.02, 1.25]) and HDL-C (fracture: HR 1.27 [1.20, 1.34]; osteoporosis: HR 1.31 [1.18, 1.46]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.85 [0.81, 0.89]; osteoporosis: HR 0.86 [0.79, 0.94]), LDL-C (fracture: HR 0.89 [0.85, 0.93]; osteoporosis: HR 0.91 [0.83, 1.00]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.75 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.05 [1.02, 1.09]) and HDL-C (RHR 1.06 [1.03, 1.09]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.30% to 40.30%), assuming causality., Conclusions: Our study reveals a complex interplay between different lipid markers and skeletal health, potentially partially mediated through BMD. Routine lipid profile assessments, including HDL-C and Apo A among other lipid traits, may be integrated into the strategies for fracture risk stratification., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: This study estimated to what extent the number of measurements of cardiometabolic risk factors (e.g., blood pressure, cholesterol, glycated haemoglobin) were impacted by the COVID-19 pandemic and whether these have recovered to expected levels., Methods and Findings: A cohort of individuals aged ≥18 years in England with records in the primary care-COVID-19 General Practice Extraction Service Data for Pandemic Planning and Research (GDPPR) were identified. Their records of 12 risk factor measurements were extracted between November 2018 and March 2024. Number of measurements per 1,000 individuals were calculated by age group, sex, ethnicity, and area deprivation quintile. The observed number of measurements were compared to a composite expectation band, derived as the union of the 95% confidence intervals of 2 estimates: (1) a projected trend based on data prior to the COVID-19 pandemic; and (2) an assumed stable trend from before pandemic. Point estimates were calculated as the mid-point of the expectation band. A cohort of 49,303,410 individuals aged ≥18 years were included. There was sharp drop in all measurements in March 2020 to February 2022, but overall recovered to the expected levels during March 2022 to February 2023 except for blood pressure, which had prolonged recovery. In March 2023 to March 2024, blood pressure measurements were below expectation by 16% (-19 per 1,000) overall, in people aged 18 to 39 (-23%; -18 per 1,000), 60 to 79 (-17%; -27 per 1,000), and ≥80 (-31%; -57 per 1,000). There was suggestion that recovery in blood pressure measurements was socioeconomically patterned. The second most deprived quintile had the highest deviation (-20%; -23 per 1,000) from expectation compared to least deprived quintile (-13%; -15 per 1,000)., Conclusions: There was a substantial reduction in routine measurements of cardiometabolic risk factors following the COVID-19 pandemic, with variable recovery. The implications for missed diagnoses, worse prognosis, and health inequality are a concern., Competing Interests: NS has consulted for and/or received speaker honoraria from Abbott Laboratories, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, Roche Diagnostics, and Sanofi; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. JV was National Clinical Director for Diabetes and Obesity at NHS England from 2013 to September 2023. JH received research grants from Amgen, British Heart Foundation, Health and Care Research Wales, and speaker honorarium from Amgen. CD is the Treasurer of European Council for Cardiovascular Research, Association of Physicians of Great Britain and Ireland, Council Member of the European Society of Hypertension, and the Vice President of Scottish Heart & Arterial disease Risk Prevention (SHARP). All other authors declared no potential conflicts of interests., (Copyright: © 2024 Ho et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Previous research on the association between physical activity (PA) and kidney function is inconsistent. The association between muscle mass and serum creatinine (SCr) may have implications for interpreting the effect of PA on estimated glomerular filtration rate (eGFR). Few studies have reported changes in physical activity and changes in kidney function., Methods: A cohort study was constructed using the UK Biobank. Changes in physical activity were self-reported as metabolic equivalent task (MET) minutes/week. eGFR was calculated using SCr and cystatin C (CysC). Cox and nonlinear regressions with restricted cubic splines were applied to explore the association between changes in physical activity and rapid decline of kidney function (RDKF, eGFR annual decrease ≥3 mL/min/1.73 m 2 ), and the annual change of eGFR. An exploratory analysis of cardiorespiratory fitness as the exposure was conducted., Results: Among 11 757 participants, the median follow-up time was 4.4 years. Participants whose PA decreased by 1000 MET minutes/week at the follow-up assessment had a 2% reduction in risk of developing RDKF SCr (HR = 0.98, 95% CI: 0.96, 1.00). In contrast, a 1000 MET minutes/week increase in PA was associated with a 4% reduction in risk of developing RDKF CysC (HR = 0.96, 95% CI: 0.93, 0.99). A PA increase of 1000 MET minutes/week was associated with eGFR CysC annual increase of 0.04 mL/min/1.73 m 2 (95% CI: 0.03, 0.06) but no significant changes in eGFR SCr ., Conclusions: In this general population study, there are differing associations between changes in PA and changes in kidney function depending on the kidney biomarker used. Increasing PA is modestly associated with improving annual eGFR CysC and reduced risk of RDKF., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcohol consumption and diet were self-reported. The diet score was created from 4 items selected using LASSO. Cox proportional hazard model showed that the diet score was monotonically associated with severe ALD risk, adjusted for sociodemographics, lifestyle factors, and alcohol consumption. Relative excess risk due to interaction analysis indicated that having a higher ALD diet score and a higher alcohol consumption simultaneously confers to 2.44 times (95% CI: 1.06-3.83) higher risk than the sum of excess risk of each factor. In this work, we show that people who have a poor diet might be more susceptible to severe ALD due to alcohol consumption., (© 2024. The Author(s).)

Participant motion in brain magnetic resonance imaging is associated with processing problems including potentially non-useable/incomplete data. This has implications for representativeness in research. Few large studies have investigated predictors of increased motion in the first instance. We exploratively tested for association between multiple psychological and physical health traits with concurrent motion during T 1 structural, diffusion, average resting-state and task functional magnetic resonance imaging in N = 52 951 UK Biobank imaging subsample participants. These traits included history of cardiometabolic, inflammatory, neurological and psychiatric conditions, as well as concurrent cognitive test scores and anthropometric traits. We tested for stability in motion in participants with longitudinal imaging data ( n = 5305, average 2.64 years later). All functional and T 1 structural motion variables were significantly intercorrelated (Pearson r range 0.3-0.8, all P < 0.001). Diffusion motion variables showed weaker correlations around r = 0.1. Most physical and psychological phenotypes showed significant association with at least one measure of increased motion including specifically in participants with complete useable data (highest β = 0.66 for diabetes versus resting-state functional magnetic resonance imaging motion). Poorer values in most health traits predicted lower odds of complete imaging data, with the largest association for history of traumatic brain injury (odds ratio = 0.720, 95% confidence interval = 0.562 to 0.923, P = 0.009). Worse psychological and physical health are consistent predictors of increased average functional and structural motion during brain imaging and associated with lower odds of complete data. Average motion levels were largely consistent across modalities and longitudinally in participants with repeat data. Together, these findings have implications for representativeness and bias in imaging studies of generally healthy population samples., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: Nine in every thousand children born in the United Kingdom have congenital heart disease, and 250,000 adults are living with the condition. This study aims to investigate the associations between congenital heart disease and educational outcomes among school-aged children in Scotland., Methods: Routine health and education databases were linked to produce a cohort of all singleton children born in Scotland and attending a local authority run primary, secondary, or special school in Scotland at some point between 2009 and 2013. Children with congenital heart disease within this cohort were compared with children unaffected by congenital conditions. Outcomes investigated were special educational need (SEN), absenteeism, exclusion, academic attainment, and unemployment. All analyses were adjusted for sociodemographic and maternity confounders. Absenteeism was investigated as a mediating factor in the associations with attainment and unemployment., Results: Of the 715,850 children, 6,295 (0.9%) had congenital heart disease and 4,412 (6.1%) had isolated congenital heart disease. Congenital heart disease and isolated congenital heart disease were both significantly associated with subsequent special educational need (OR 3.45, 95% CI 3.26-3.65, p < 0.001 and OR 1.98, 95% CI 1.84-2.13, p < 0.001 respectively), absenteeism (IRR 1.13, 95% CI 1.10-1.16, p < 0.001 and IRR 1.10, 95% CI 1.06-1.13, p < 0.001 respectively), and low academic attainment (OR 1.69, 95% CI 1.39-2.07, p < 0.001 and OR 1.35, 95% CI 1.07-1.69, p = 0.011 respectively). Neither congenital heart disease nor isolated congenital heart disease were associated with school exclusion. Only congenital heart disease (OR 1.21, 95% CI 1.03-1.42, p = 0.022) but not isolated congenital heart disease was associated with unemployment. When days absent were included in the analyses investigating attainment and unemployment, the conclusions were not altered., Conclusion: Children with congenital heart disease have greater special educational need, lower school attendance, attain lower examination grades and have greater unemployment compared to peers. In addition to healthcare support, affected children need educational support to avoid additional impact on their long-term wellbeing., (© 2024. The Author(s).)

Background: Obesity and central obesity are multifactorial conditions with genetic and non-genetic (lifestyle and environmental) contributions. There is incomplete understanding of whether lifestyle modifies the translation from respective genetic risks into phenotypic obesity and central obesity, and to what extent genetic predisposition to obesity and central obesity is mediated via lifestyle factors., Methods: This is a cross-sectional study of 201,466 (out of approximately 502,000) European participants from UK Biobank and tested for interactions and mediation role of lifestyle factors (diet quality; physical activity levels; total energy intake; sleep duration, and smoking and alcohol intake) between genetic risk for obesity and central obesity. BMI-PRS and WHR-PRS are exposures and obesity and central obesity are outcomes., Results: Overall, 42.8% of the association between genetic predisposition to obesity and phenotypic obesity was explained by lifestyle: 0.9% by mediation and 41.9% by effect modification. A significant difference between men and women was found in central obesity; the figures were 42.1% (association explained by lifestyle), 1.4% (by mediation), and 40.7% (by modification) in women and 69.6% (association explained by lifestyle), 3.0% (by mediation), and 66.6% (by modification) in men., Conclusions: A substantial proportion of the association between genetic predisposition to obesity/central obesity and phenotypic obesity/central obesity was explained by lifestyles. Future studies with repeated measures of obesity and lifestyle would be needed to clarify causation., (© 2024. The Author(s).)

Background: Previous studies suggest an association between schizophrenia and stroke, but no studies have investigated stroke subtypes. We examined potential causal associations between schizophrenia and a range of atherosclerotic, embolic, and hemorrhagic stroke outcomes., Methods and Results: Two-sample Mendelian randomization analyses were conducted. The summary-level data (restricted to European ancestry) were obtained for schizophrenia and stroke: ischemic stroke, large-artery stroke, small-vessel stroke, cardioembolic stroke, and intracerebral hemorrhage. The associations between schizophrenia and each outcome were analyzed by an inverse variance weighting method primarily and Mendelian randomization Egger, weighted median, and weighted mode subsequently. The presence of pleiotropy was also tested by Cochran Q statistic, I 2 index, and Mendelian randomization Egger intercept with scatter and funnel plots. We found associations between schizophrenia and cardioembolic stroke (odds ratio [OR], 1.070 [95% CI, 1.023-1.119]) and intracerebral hemorrhage (OR, 1.089 [95% CI, 1.005-1.180]) using inverse variance weighting. Little evidence of associations with the other stroke subtypes was found. Different Mendelian randomization methods corroborated the association with cardioembolic stroke but not intracerebral hemorrhage., Conclusions: We have provided evidence of a potentially causal association between schizophrenia and cardioembolic stroke. Our findings suggest that cardiac evaluation should be considered for those with schizophrenia.

Background: Preliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations., Methods: We undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables., Results: Data from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively., Conclusions: Cholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women., (© 2023. The Author(s).)

Long-COVID prevalence estimates vary widely and should take account of symptoms that would have occurred anyway. Here we determine the prevalence of symptoms attributable to SARS-CoV-2 infection, taking account of background rates and confounding, in a nationwide population cohort study of 198,096 Scottish adults. 98,666 (49.8%) had symptomatic laboratory-confirmed SARS-CoV-2 infections and 99,430 (50.2%) were age-, sex-, and socioeconomically-matched and never-infected. While 41,775 (64.5%) reported at least one symptom 6 months following SARS-CoV-2 infection, this was also true of 34,600 (50.8%) of those never-infected. The crude prevalence of one or more symptom attributable to SARS-CoV-2 infection was 13.8% (13.2%,14.3%), 12.8% (11.9%,13.6%), and 16.3% (14.4%,18.2%) at 6, 12, and 18 months respectively. Following adjustment for potential confounders, these figures were 6.6% (6.3%, 6.9%), 6.5% (6.0%, 6.9%) and 10.4% (9.1%, 11.6%) respectively. Long-COVID is characterised by a wide range of symptoms that, apart from altered taste and smell, are non-specific. Care should be taken in attributing symptoms to previous SARS-CoV-2 infection., (© 2023. The Author(s).)

Background We tested the potential of the Secondary Manifestations of Arterial Disease (SMART2) risk score for use in patients undergoing coronary artery bypass grafting. Methods and Results We conducted an external validation of the SMART2 score in a racially diverse high-risk national cohort (2010-2019) that underwent isolated coronary artery bypass grafting. We calculated the preoperative SMART2 score and modeled the 5-year major adverse cardiovascular event (cardiovascular mortality+myocardial infarction+stroke) incidence. We evaluated SMART2 score discrimination at 5 years using c-statistic and calibration with observed/expected ratio and calibration plots. We analyzed the potential clinical benefit using decision curves. We repeated these analyses in clinical subgroups, diabetes, chronic kidney disease, and polyvascular disease, and separately in White and Black patients. In 27 443 (mean age, 65 years; 10% Black individuals) US veterans undergoing coronary artery bypass grafting (2010-2019) nationwide, the 5-year major adverse cardiovascular event rate was 25%; 27% patients were in high predicted risk (>30% 5-year major adverse cardiovascular events). SMART2 score discrimination (c-statistic: 64) was comparable to the original study (c-statistic: 67) and was best in patients with chronic kidney disease (c-statistic: 66). However, it underpredicted major adverse cardiovascular event rates in the whole cohort (observed/expected ratio, 1.45) as well as in all studied subgroups. The SMART2 score performed better in White than Black patients. On decision curve analysis, the SMART2 score provides a net benefit over a wide range of risk thresholds. Conclusions The SMART2 model performs well in a racially diverse coronary artery bypass grafting cohort, with better predictive capabilities at the upper range of baseline risk, and can therefore be used to guide secondary preventive pharmacotherapy.

Background: Attention-deficit hyperactivity disorder (ADHD) affects around 1 in 20 children and is associated with life-long sequelae. Previous studies of the association between Apgar score and ADHD have reported inconsistent findings., Methods: Record linkage of maternity, prescribing and school pupil census databases was used to conduct a population e-cohort study of singleton children born in Scotland and attending school in Scotland at any point between 2009 and 2013. Binary logistic regression analysis was used to investigate the association between 5-min Apgar score and treated ADHD adjusting for sociodemographic and maternity confounders., Results: Of the 758,423 children, 7,292 (0.96%) received ADHD medication. The results suggested a potential dose-response relationship between Apgar score and treated ADHD independent of confounders. Referent to an Apgar score of 10, risk of treated ADHD was higher for scores of 0-3 (adjusted OR 1.76, 95% CI 1.32-2.34), 4-6 (adjusted OR 1.50, 95% CI 1.21-1.86) and even 7-9 (adjusted OR 1.26, 95% CI 1.18-1.36) which are traditionally considered within the normal range., Conclusions: In addition to reinforcing the need to maximise Apgar score through good obstetric practice, the findings suggest that Apgar score may be useful in predicting future risk of ADHD and therefore facilitating early diagnosis and treatment., (© 2023. The Author(s).)

Background: Evidence from the UK from the early stages of the covid-19 pandemic showed that people with Intellectual Disabilities (ID) had higher rates of covid-19 mortality than people without ID. However, estimates of the magnitude of risk vary widely; different studies used different time periods; and only early stages of the pandemic have been analysed. Existing analyses of risk factors have also been limited. The objective of this study was to investigate covid-19 mortality rates, hospitalisation rates, and risk factors in people with ID in England up to the end of 2021., Methods: Retrospective cohort study of all people with a laboratory-confirmed SARS-CoV-2 infection or death involving covid-19. Datasets covering primary care, secondary care, covid-19 tests and vaccinations, prescriptions, and deaths were linked at individual level., Results: Covid-19 carries a disproportionately higher risk of death for people with ID, above their already higher risk of dying from other causes, in comparison to those without ID. Around 2,000 people with ID had a death involving covid-19 in England up to the end of 2021; approximately 1 in 180. The covid-19 standardized mortality ratio was 5.6 [95% CI 5.4, 5.9]. People with ID were also more likely to be hospitalised for covid-19 than people without ID. The main determinants of severe covid-19 outcomes (deaths and/or hospitalisations) in both populations were age, multimorbidity and vaccination status. The key factor responsible for the higher risk of severe covid-19 in the ID population was a much higher prevalence of multimorbidity in this population. AstraZeneca vaccine was slightly less effective in preventing severe covid-19 outcomes among people with ID than among people without ID., Conclusions: People with ID should be considered a priority group in future pandemics, such as shielding and vaccinations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Happiness is a fundamental human affective trait, but its biological basis is not well understood. Using a novel approach, we construct LDpred-inf polygenic scores of a general happiness measure in 2 cohorts: the Adolescent Brain Cognitive Development (ABCD) cohort (N = 15,924, age range 9.23-11.8 years), the Add Health cohort (N = 9129, age range 24.5-34.7) to determine associations with several well-being and happiness measures. Additionally, we investigated associations between genetic scores for happiness and brain structure in ABCD (N = 9626, age range (8.9-11) and UK Biobank (N = 16,957, age range 45-83). We detected significant (p.FDR < 0.05) associations between higher genetic scores vs. several well-being measures (best r 2  = 0.019) in children of multiple ancestries in ABCD and small yet significant correlations with a happiness measure in European participants in Add Health (r 2  = 0.004). Additionally, we show significant associations between lower genetic scores for happiness with smaller structural brain phenotypes in a white British subsample of UK Biobank and a white sub-sample group of ABCD. We demonstrate that the genetic basis for general happiness level appears to have a consistent effect on happiness and wellbeing measures throughout the lifespan, across multiple ancestral backgrounds, and multiple brain structures., (© 2023. Springer Nature Limited.)

Objective: The study aim was to investigate associations of 11 anthropometric measures with incident type 2 diabetes and compare their predictive performance., Methods: This prospective cohort study included 161,127 White European UK Biobank participants who were free of diabetes at baseline. Anthropometric measures included height, weight, BMI, A Body Shape Index, waist circumference, waist to hip ratio, waist to height ratio (WHtR), hip circumference, visceral adiposity index, hip index, and anthropometric risk index. The associations were examined using Cox proportional hazard models. The differences in C-index were used to compare predictive performance between BMI and other anthropometric measures., Results: The median follow-up was 10.0 (interquartile range: 9.3-10.8) years, during which 6315 participants developed type 2 diabetes. All markers except height and hip index were positively associated with incident type 2 diabetes. The strongest associations were found for WHtR (hazard ratio per 1-SD increment: 2.27 [95% CI 2.19-2.35] in women; 1.96 [95% CI 1.90-2.01] in men). Compared with BMI, WHtR and anthropometric risk index had significantly better type 2 diabetes risk discrimination., Conclusions: Although most adiposity markers were associated with type 2 diabetes, the magnitude of the associations differed. WHtR had the strongest associations and predictive ability for type 2 diabetes and thus could be a more suitable marker for clinical use., (© 2023 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) are associated with an increased risk of cardiovascular diseases, including venous thromboembolism (VTE). The reasons for this are complex and include obesity, smoking, and use of hormones and psychotropic medications. Genetic studies have increasingly provided evidence of the shared genetic risk of psychiatric and cardiometabolic illnesses. This study aimed to determine whether a genetic predisposition to MDD, BD, or SCZ is associated with an increased risk of VTE. Genetic correlations using the largest genome-wide genetic meta-analyses summary statistics for MDD, BD, and SCZ (Psychiatric Genetics Consortium) and a recent genome-wide genetic meta-analysis of VTE (INVENT Consortium) demonstrated a positive association between VTE and MDD but not BD or SCZ. The same summary statistics were used to construct polygenic risk scores for MDD, BD, and SCZ in UK Biobank participants of self-reported White British ancestry. These were assessed for impact on self-reported VTE risk (10 786 cases, 285 124 controls), using logistic regression, in sex-specific and sex-combined analyses. We identified significant positive associations between polygenic risk for MDD and the risk of VTE in men, women, and sex-combined analyses, independent of the known risk factors. Secondary analyses demonstrated that this association was not driven by those with lifetime experience of mental illness. Meta-analyses of individual data from 6 additional independent cohorts replicated the sex-combined association. This report provides evidence for shared biological mechanisms leading to MDD and VTE and suggests that, in the absence of genetic data, a family history of MDD might be considered when assessing the risk of VTE., (© 2023 by The American Society of Hematology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Being breastfed is associated with lower cardiovascular risk factors but, to date, no studies have demonstrated a protective effect on cardiovascular disease (CVD). This study aims to address the limitations of previous studies, specifically insufficient statistical power and residual confounding, to determine if such association exists., Methods: This is a population-based retrospective cohort study of 320 249 men and women aged 40-69 years. Breastfeeding status was self-reported. CVD and myocardial infarction (MI) events and deaths based via linkage to hospitalization and death records., Results: Overall, 28 469 (8.4%) participants experienced a CVD event and 5174 (1.6%) experienced an MI. Following adjustment for sociodemographic, lifestyle and early life confounders, breastfeeding was associated with a reduced risk of CVD events (HR 0.97, 95% CI 0.94-1.00, P = 0.041), CVD deaths (HR 0.91, 95% CI 0.84-0.98, P = 0.017), MI events (HR 0.93, 95% CI 0.87-0.99, P = 0.033) and MI deaths (HR 0.81, 95% CI 0.67-0.98, P = 0.026)., Conclusions: Child health benefits of breastfeeding are well established. However, the benefits of breastfeeding may extend into later life reinforcing the need to encourage and support breastfeeding., (© The Author(s) 2023. Published by Oxford University Press on behalf of Faculty of Public Health.)

Background: The Emergency Medical Retrieval Service (EMRS) has provided national pre-hospital critical care and aeromedical retrieval in Scotland since 2010. This study investigates trends in the service and patients attended over the last decade; and factors associated with clinical deterioration and pre-hospital death., Methods: A retrospective cohort study was conducted of all service taskings over ten years (2011-2020 inclusive). The EMRS electronic database provided data on location, sociodemographic factors, diagnoses, physiological measurements, clinical management, and pre-hospital deaths. Binary logistic regression models were used to determine change in physiology in pre-hospital care, and factors associated with pre-hospital death. Geospatial modelling, using road and air travel time models, was used to explore transfer times., Results: EMRS received 8,069 taskings over the study period, of which 2,748 retrieval and 3,633 pre-hospital critical care missions resulted in patient contact. EMRS was more commonly dispatched to socioeconomically deprived areas for pre-hospital critical care incidents (Spearman's rank correlation, r(8)=-0.75, p = 0.01). In multivariate analysis, systolic blood pressure < 90mmHg, respiratory rate < 6/min or > 30/min, and Glasgow Coma Score ≤ 14 were associated with pre-hospital mortality independent of demographic factors. Geospatial modelling suggested that aeromedical retrieval reduced the mean time to a critical care unit by 1 h 46 min compared with road/ferry transportation., Conclusion: EMRS continues to develop, delivering Pre-Hospital and Retrieval Medicine across Scotland and may have a role in addressing health inequalities, including socioeconomic deprivation and geographic isolation. Age, specific distances from care, and abnormal physiology are associated with death in pre-hospital critical care., (© 2023. Norwegian Air Ambulance Foundation.)

Background: There is evidence that child maltreatment is associated with shorter telomere length in early life., Aims: This study aims to examine if child maltreatment is associated with telomere length in middle- and older-age adults., Method: This was a retrospective cohort study of 141 748 UK Biobank participants aged 37-73 years at recruitment. Leukocyte telomere length was measured with quantitative polymerase chain reaction, and log-transformed and scaled to have unit standard deviation. Child maltreatment was recalled by participants. Linear regression was used to analyse the association., Results: After adjusting for sociodemographic characteristics, participants with three or more types of maltreatment presented with the shortest telomere lengths ( β = -0.05, 95% CI -0.07 to -0.03; P < 0.0001), followed by those with two types of maltreatment ( β = -0.02, 95% CI -0.04 to 0.00; P = 0.02), referent to those who had none. When adjusted for depression and post-traumatic stress disorder, the telomere lengths of participants with three or more types of maltreatment were still shorter ( β = -0.04, 95% CI -0.07 to -0.02; P = 0.0008). The telomere lengths of those with one type of maltreatment were not significantly different from those who had none. When mutually adjusted, physical abuse ( β = -0.05, 95% CI -0.07 to -0.03; P < 0.0001) and sexual abuse ( β = -0.02, 95% CI -0.04 to 0.00; P = 0.02) were independently associated with shorter telomere length., Conclusions: Our findings showed that child maltreatment is associated with shorter telomere length in middle- and older-aged adults, independent of sociodemographic and mental health factors.

Background: A cancer diagnosis during childhood greatly disrupts the lives of those affected, causing physical and psychological challenges. We aim to investigate educational outcomes among schoolchildren with a previous cancer diagnosis compared to their peers., Methods: Individual records from four national education databases and three national health databases were linked to construct a cohort of all singleton schoolchildren born in Scotland attending Scottish local-authority schools between 2009-2013. Pupils previously diagnosed with any cancer, haematological cancers, and central nervous system (CNS) cancers, were compared to their unaffected peers with respect to five educational outcomes: special educational need (SEN), absenteeism, school exclusion, academic attainment, and unemployment. Analyses were adjusted for sociodemographic and maternity factors and chronic conditions., Results: Of 766,217 pupils, 1,313 (0.17%) had a previous cancer diagnosis. Children with any cancer had increased odds of SEN (OR 3.26, 95% CI 2.86-3.71), absenteeism (IRR 1.82, 95% CI 1.70-1.94), and low attainment (OR 2.15, 95% CI 1.52-3.03) compared to their peers. Similar findings were observed for haematological (SEN OR 2.62, 95% CI 2.12-3.24; absenteeism IRR 2.04, 95% CI 1.85-2.25; low attainment OR 2.17, 95% CI 1.31-3.61) and CNS (SEN OR 6.44, 95% CI 4.91-8.46; absenteeism IRR 1.75, 95% CI 1.51-2.04; low attainment OR 3.33, 95% CI 1.52-7.30) cancers. Lower exclusions were observed among children with any cancer (IRR 0.51, 95% CI 0.31-0.83) and CNS cancer (IRR 0.20, 95% CI 0.06-0.61). No associations were observed with unemployment., Conclusions: This study highlights the wider impacts of childhood cancer on educational outcomes. These children need to be supported, as poor educational outcomes can further impact later health., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Baughan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Growing evidence suggests that individuals with anxiety disorder have an elevated risk of cardiovascular disease (CVD) but few studies have assessed this association independently of or jointly with depression., Methods: We conducted a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder, depression, and CVDs were ascertained through linked hospital admission and mortality data. Individual and joint associations between anxiety disorder and depression and CVD overall, as well as each of myocardial infarction, stroke/transient ischemic attack, and heart failure, were analyzed using Cox proportional hazard models and interaction tests., Results: Among the 431,973 participants, the risk of CVD was higher among those who had been diagnosed with anxiety disorder only (hazard ratio [HR] 1.72; 95% confidence interval [CI] 1.32-2.24), depression only (HR 2.07; 95% CI 1.79-2.40), and both conditions (HR 2.89; 95% CI 2.03-4.11) compared to those without these conditions, respectively. There was very little evidence of multiplicative or additive interaction. Results were similar for myocardial infarction, stroke/transient ischemic attack, and heart failure., Conclusions: Having anxiety is associated with the same magnitude of increased risk of CVD among people who do not have depression and those who do. Anxiety disorder should be considered for inclusion in CVD risk prediction and stratification, in addition to depression.

Previous studies on the natural history of long-COVID have been few and selective. Without comparison groups, disease progression cannot be differentiated from symptoms originating from other causes. The Long-COVID in Scotland Study (Long-CISS) is a Scotland-wide, general population cohort of adults who had laboratory-confirmed SARS-CoV-2 infection matched to PCR-negative adults. Serial, self-completed, online questionnaires collected information on pre-existing health conditions and current health six, 12 and 18 months after index test. Of those with previous symptomatic infection, 35% reported persistent incomplete/no recovery, 12% improvement and 12% deterioration. At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group and adjusted for confounders. Conversely, late onset dry and productive cough, and hearing problems were more likely following SARS-CoV-2 infection., (© 2023. The Author(s).)

Background: Most studies investigating the association between physical activity (PA) and the risk of type 2 diabetes are derived from self-reported questionnaires, with limited evidence using device-based measurements. Therefore, this study aimed to investigate the dose-response relationship between device-measured PA and incident type 2 diabetes., Methods: This prospective cohort study included 40,431 participants of the UK Biobank. Wrist-worn accelerometers were used to estimate total, light, moderate, vigorous and moderate-to-vigorous PA. The associations between PA and incident type 2 diabetes were analysed using Cox-proportional hazard models. The mediating role of body mass index (BMI) was tested under a causal counterfactual framework., Results: The median follow-up period was 6.3 years (IQR: 5.7-6.8), with 591 participants developing type 2 diabetes. Compared to those achieving < 150 min/week of moderate PA, people achieving 150-300, 300-600 and > 600 min/week were at 49% (95% CI 62-32%), 62% (95% CI 71-50%) and 71% (95% CI 80-59%) lower risk of type 2 diabetes, respectively. For vigorous PA, compared to those achieving < 25 min/week, individuals achieving 25-50, 50-75 and > 75 min/week were at 38% (95% CI 48-33%), 48% (95% CI 64-23%) and 64% (95% CI 78-42%) lower type 2 diabetes risk, respectively. Twelve per cent and 20% of the associations between vigorous and moderate PA and type 2 diabetes were mediated by lower BMI, respectively., Conclusions: PA has clear dose-response relationship with a lower risk of type 2 diabetes. Our findings support the current aerobic PA recommendations but suggest that additional PA beyond the recommendations is associated with even greater risk reduction., Trial Registration: The UK Biobank study was approved by the North West Multi-Centre Research Ethics Committee (Ref 11/NW/0382 on June 17, 2011)., (© 2023. The Author(s).)

Background: While special educational needs (SEN) are increasingly recorded among schoolchildren, infant breastfeeding has been associated with reduced incidence of childhood physical and mental health problems. This study investigated relationships between infant feeding method and risk of all-cause and cause-specific SEN., Methods and Findings: A population cohort of schoolchildren in Scotland was constructed by linking together health (maternity, birth, and health visitor records) and education (annual school pupil census) databases. Inclusion was restricted to singleton children, born in Scotland from 2004 onwards with available breastfeeding data and who attended local authority mainstream or special schools between 2009 and 2013. Generalised estimating equation models with a binomial distribution and logit link function investigated associations between infant feeding method at 6 to 8 weeks and all-cause and cause-specific SEN, adjusting for sociodemographic and maternity factors. Of 191,745 children meeting inclusion criteria, 126,907 (66.2%) were formula-fed, 48,473 (25.3%) exclusively breastfed, and 16,365 (8.5%) mixed-fed. Overall, 23,141 (12.1%) children required SEN. Compared with formula feeding, mixed feeding and exclusive breastfeeding, respectively, were associated with decreased all-cause SEN (OR 0.90, 95% CI [0.84,0.95], p < 0.001 and 0.78, [0.75,0.82], p < 0.001), and SEN attributed to learning disabilities (0.75, [0.65,0.87], p < 0.001 and 0.66, [0.59,0.74], p < 0.001), and learning difficulties (0.85, [0.77,0.94], p = 0.001 and 0.75, [0.70,0.81], p < 0.001). Compared with formula feeding, exclusively breastfed children had less communication problems (0.81, [0.74,0.88], p = 0.001), social-emotional-behavioural difficulties (0.77, [0.70,0.84], p = 0.001), sensory impairments (0.79, [0.65,0.95], p = 0.01), physical motor disabilities (0.78, [0.66,0.91], p = 0.002), and physical health conditions (0.74, [0.63,0.87], p = 0.01). There were no significant associations for mixed-fed children (communication problems (0.94, [0.83,1.06], p = 0.312), social-emotional-behavioural difficulties (0.96, [0.85,1.09], p = 0.541), sensory impairments (1.07, [0.84,1.37], p = 0.579), physical motor disabilities (0.97, [0.78,1.19], p = 0.754), and physical health conditions (0.93, [0.74,1.16], p = 0.504)). Feeding method was not significantly associated with mental health conditions (exclusive 0.58 [0.33,1.03], p = 0.061 and mixed 0.74 [0.36,1.53], p = 0.421) or autism (exclusive 0.88 [0.77,1.01], p = 0.074 and mixed 1.01 [0.84,1.22], p = 0.903). Our study was limited since only 6- to 8-week feeding method was available precluding differentiation between never-breastfed infants and those who stopped breastfeeding before 6 weeks. Additionally, we had no data on maternal and paternal factors such as education level, IQ, employment status, race/ethnicity, or mental and physical health., Conclusions: In this study, we observed that both breastfeeding and mixed feeding at 6 to 8 weeks were associated with lower risk of all-cause SEN, and SEN attributed to learning disabilities and learning difficulty. Many women struggle to exclusively breastfeed for the full 6 months recommended by WHO; however, this study provides evidence that a shorter duration of nonexclusive breastfeeding could nonetheless be beneficial with regard to the development of SEN. Our findings augment the existing evidence base concerning the advantages of breastfeeding and reinforce the importance of breastfeeding education and support., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Adams et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although non-alcoholic fatty liver disease (NAFLD) is linked to inflammation, whether an inflammatory diet increases the risk of NAFLD is unclear. This study aimed to examine the association between the Energy-adjusted Diet Inflammatory Index (E-DII) score and severe NAFLD using UK Biobank., Methods: This prospective cohort study included 171,544 UK Biobank participants. The E-DII score was computed using 18 food parameters. Associations between the E-DII and incident severe NAFLD (defined as hospital admission or death) were first investigated by E-DII categories (very/moderately anti-inflammatory [E-DII <  - 1], neutral [E-DII - 1 to 1] and very/moderately pro-inflammatory [E-DII > 1]) using Cox proportional hazard models. Nonlinear associations were investigated using penalised cubic splines fitted into the Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors., Results: Over a median follow-up of 10.2 years, 1489 participants developed severe NAFLD. After adjusting for confounders, individuals in the very/moderately pro-inflammatory category had a higher risk (HR: 1.19 [95% CI: 1.03 to 1.38]) of incident severe NAFLD compared with those in the very/moderately anti-inflammatory category. There was some evidence of nonlinearity between the E-DII score and severe NAFLD., Conclusions: Pro-inflammatory diets were associated with a higher risk of severe NAFLD independent of confounders such as the components of the metabolic syndrome. Considering there is no recommended treatment for the disease, our findings suggest a potential means to lower the risk of NAFLD., (© 2023. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Visnick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Diet, the most important modulator of inflammatory and immune responses, may affect COVID-19 incidence and disease severity. Data from 196,154 members of the UK biobank had at least one 24 h dietary recall. COVID-19 outcomes were based on PCR testing, hospital admissions, and death certificates. Adjusted Poisson regression analyses were performed to estimate the risk ratios (RR) and their 95% confidence intervals (CI) for dietary inflammatory index (DII)/energy-adjusted DII (E-DII) scores. Models were adjusted for sociodemographic factors, comorbidities, smoking status, physical activity, and sleep duration. Between January 2020 and March 2021, there were 11,288 incident COVID-19 cases, 1270 COVID-19-related hospitalizations, and 315 COVID-19-related deaths. The fully adjusted model showed that participants in the highest (vs. lowest) DII/E-DII quintile were at 10-17% increased risk of COVID-19 (DII: RR Q5 vs . Q1 = 1.10, 95% CI 1.04-1.17, P trend < 0.001; E-DII: RR Q5 vs . Q1 = 1.17, 95% CI 1.10-1.24, P trend < 0.001) and ≈40% higher risk was observed for disease severity (DII: RR Q5 vs . Q1 = 1.40, 95% CI 1.18-1.67, P trend < 0.001; E-DII: RR Q5 vs . Q1 = 1.39, 95% CI 1.16-1.66, P trend < 0.001). There was a 43% increased risk of COVID-19-related death in the highest DII quintile (RR Q5 vs . Q1 = 1.43, 95% CI 1.01-2.01, P trend = 0.04). About one-quarter of the observed positive associations between DII and COVID-19-related outcomes were mediated by body mass index (25.8% for incidence, 21.6% for severity, and 19.8% for death). Diet-associated inflammation increased the risk of COVID-19 infection, severe disease, and death.