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Background and Objectives: The aging population is growing faster than all other demographic strata. With older age comes a greater risk of health conditions such as obesity and high blood pressure (BP). These cardiometabolic risk factors (CMRs) exhibit prominent sex differences in midlife and aging, yet their influence on brain health in females vs males is largely unexplored. In this study, we investigated sex differences in relationships between BP, body mass index (BMI), and brain age over time and tested for interactions with APOE ε4 genotype ( APOE4 ), a known genetic risk factor of Alzheimer disease., Methods: The sample included participants from 2 United Kingdom-based longitudinal birth cohorts, the Lothian Birth Cohort (1936) and Insight 46 (1946). Participants with MRI data from at least 1 time point were included to evaluate sex differences in associations between CMRs and brain age. The open-access software package brainageR 2.1 was used to estimate brain age for each participant. Linear mixed-effects models were used to assess the relationships between brain age, BMI, BP, and APOE4 status (i.e., carrier vs noncarrier) in males and females over time., Results: The combined sample comprised 1,120 participants (48% female) with a mean age (SD) of 73 (0.72) years in the Lothian Birth Cohort and 71 (0.68) years in Insight 46 at the time point 1 assessment. Approximately 30% of participants were APOE4 carriers. Higher systolic and diastolic BP was significantly associated with older brain age in females only (β = 0.43-0.56, p < 0.05). Among males, higher BMI was associated with older brain age across time points and APOE4 groups (β = 0.72-0.77, p < 0.05). In females, higher BMI was linked to older brain age among APOE4 noncarriers (β = 0.68-0.99, p < 0.05), whereas higher BMI was linked to younger brain age among carriers, particularly at the last time point (β = -1.75, p < 0.05)., Discussion: This study indicates sex-dependent and time-dependent relationships between CMRs, APOE4 status, and brain age. Our findings highlight the necessity of sex-stratified analyses to elucidate the role of CMRs in individual aging trajectories, providing a basis for developing personalized preventive interventions.

Background: The association between exposure to air pollutants and cardiovascular disease (CVD) trajectory in individuals with circadian syndrome remains inconclusive., Methods: The individual exposure levels of air pollutants, including particulate matter (PM) with aerodynamic diameter ≤ 2.5 μm (PM 2.5 ), PM with aerodynamic diameter ≤ 10 μm (PM 10 ), PM 2.5 absorbance , PM with aerodynamic diameter between 2.5 μm and 10 μm, nitrogen dioxide (NO 2 ), nitrogen oxides (NO x ), and air pollution score (overall air pollutants exposure), were estimated for 48,850 participants with circadian syndrome from the UK Biobank. Multistate regression models were employed to estimate associations between exposure to air pollutants and trajectories from circadian syndrome to CVD/CVD subtypes (including coronary heart disease [CHD], atrial fibrillation [AF], heart failure [HF], and stroke) and death. Mediation roles of CVD/CVD subtypes in the associations between air pollutants and death were evaluated., Results: After a mean follow-up time over 12 years, 12,570 cases of CVD occurred, including 8192 CHD, 1693 AF, 1085 HF, and 1600 stroke cases. In multistate model, per-interquartile range increment in PM 2.5 (hazard ratio: 1.08; 95 % confidence interval: 1.06, 1.10), PM 10 (1.04; 1.01, 1.06), PM 2.5 absorbance (1.04; 1.02, 1.06), NO 2 (1.07; 1.03, 1.11), NO x (1.08; 1.04, 1.12), or air pollution score (1.06; 1.03, 1.08) was associated with trajectory from circadian syndrome to CVD. Significant associations between the above-mentioned air pollutants and trajectories from circadian syndrome and CVD to death were observed. CVD, particularly CHD, significantly mediated the associations of PM 2.5 , NO 2 , NO x , and air pollution score with death., Conclusions: Long-term exposure to air pollutants during circadian syndrome was associated with subsequent CVD and death. CHD emerged as the most prominent CVD subtype in CVD progression driven by exposure to air pollutants during circadian syndrome. Our study highlights the importance of controlling air pollutants exposure and preventing CHD in people with circadian syndrome., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: In the past few decades, research on the association between indoor temperature and sleep has primarily used laboratory rather than field data collected in epidemiological cohorts., Methods: Secondary data on 2493 individuals aged 43 years was obtained from the National Survey of Health and Development (NSHD). Logistic regression models were used to investigate the associations between temperatures (indoor at home, spot measurement when the nurses visited during the day; and outdoor, monthly average) and self-reported sleep disturbances, adjusting for socio-demographics, health variables, housing variables, and temperature-related variables., Results: Associations were found between daytime indoor temperature with difficulty initiating (OR: 0.95, 95%CI: 0.91-0.98) and maintaining sleep (OR: 0.96, 95%CI: 0.93-0.99). Compared with neutral indoor temperatures (17-28 °C), low indoor temperature (≤17 °C) was associated with difficulty initiating sleep (OR: 1.79, 95%CI: 1.21-2.65). Stratified analysis results across tertiles showed that associations with difficulty initiating (OR: 0.87, 95%CI: 0.77-0.99) and maintaining sleep (OR: 0.88, 95%CI: 0.79-0.98) were observed respectively in the lowest (≤20 °C) and highest tertile (≥23 °C) of indoor temperature. There was no association between outdoor temperature and self-reported sleep disturbances in this study., Conclusion: In this first UK-based epidemiology study investigating temperature and sleep, self-reported sleep disturbances were associated with residential daytime indoor temperatures. Low indoor temperature had significantly higher odds ratio for difficulty initiating sleep compared with the neutral indoor temperature. A warmer indoor environment might be more suitable for sleep maintenance than sleep initiation. Indoor temperature in this study was a superior indicator of sleep disturbances than outdoor temperature. Although these findings are based on a UK sample, they may be relevant to other high-income settings with similar housing stock and climatic conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen-detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03-1.11) than screen-detected cancer (RR 1.27, 1.23-1.30); having a first-degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68-1.95) than screen-detected cancer (RR 1.52, 1.43-1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72-1.99) than screen-detected cancer (RR 1.34, 1.26-1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Cohort studies linking greenspace exposure to a lower risk of obesity-related cancer (ORC) are scarce. Existing evidence on site-specific cancers has predominantly relied on non-specific greenspace measures, including vegetation indices. We examined the associations of total greenspace, private residential gardens, and other greenspace types with the risk of being diagnosed with overall and site-specific ORC., Methods: We used data from the participants in the UK Biobank recruited between 2006 and 2010 and censored until December 31, 2016. We defined greenspace variables using Ordnance Survey MasterMap™ greenspace categories. The incidence of ORC was ascertained through data linkage to cancer registries. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models and adjusted for covariates. We conducted mediation and modification analysis by physical activity, serum 25-hydroxyvitamin D [25(OH)D], and particulate matter air pollution with an aerodynamic diameter ≤ 2.5 (PM 2.5 ) and nitrogen dioxide (NO 2 ), as well as subgroup analysis by covariates., Results: Among 279,326 participants, 9550 developed ORC over a median follow-up period of 7.82 years. An increase in private residential gardens within a 100 m buffer was associated with a decreased risk of overall ORC (HR:0.92; 95 % CI: 0.88, 0.96), breast cancer (HR: 0.91; 95 % CI: 0.84, 0.98), and uterine cancer (HR:0.80; 95 % CI: 0.67, 0.96). There was no association between other greenspace types and ORC, except for uterine cancer. The association for ORC was partly mediated by NO 2 and modified by physical activity levels, 25(OH)D, PM 2.5, and NO 2 , and sociodemographic factors, including sex and neighbourhood socioeconomic status., Conclusion: Increased exposure to private residential gardens may lower the risk of being diagnosed with obesity-related cancer, particularly breast and uterine cancer. Future studies might move beyond considering greenspace quantity to explore functional types of greenspace exposure that should be prioritized for targeted health intervention and cancer prevention., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nicholas J Osborne reports a relationship with Reckitt Benckiser Australia Pty Ltd. that includes: speaking and lecture fees. Nicholas J Osborne reports a relationship with Taylor & Francis Group that includes: consulting or advisory. Nicholas J Osborne reports a relationship with Federal Court of Australia that includes: paid expert testimony. The authors declare no other competing interests If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Previous research indicates an association of body dysmorphic disorder (BDD) with suicidal thoughts and behaviours, but has largely relied on small cohorts drawn from specialist clinics., Methods: Anonymised health-records from the South London and Maudsley NHS Foundation Trust between 2007 and 2019 were systematically searched using the Clinical Record Interactive Search data system., Results: 298 patients diagnosed with BDD between age 12 and 65 years were identified. 206 (69 %) had experienced lifetime suicidal ideation. 149 (50 %) had recorded lifetime acts of self-harm or suicide attempts, most commonly involving cutting and self-poisoning. Rates of self-harm/suicide attempts were similar in those diagnosed before or after 18 years. Comorbid depression was associated with suicidal ideation (OR: 4.26 95% CI 2.07-9.72). Additionally, comorbid depression, OCD and anxiety were all associated with self-harm/suicide attempts (OR: 1.94 95% CI 1.15-3.31, OR: 1.99 95% CI 1.09-3.73, and OR: 1.93 95% CI 1.09-3.45, respectively). The presence of two or more psychiatric comorbidities was associated with a significantly elevated likelihood of suicidal ideation (OR: 7.06 95% CI 2.80-21.7) and self-harm/suicide attempts (OR: 4.62 95% CI 2.32-9.62)., Limitations: It is likely that BDD was under-diagnosed in the cohort, and those identified may not be representative. Additionally, the frequency and detail with which suicidal thoughts and behaviours were assessed varied and may also represent underestimates., Conclusions: Suicidal ideation and self-harm/suicide attempts are common among individuals with BDD accessing mental health services. Psychiatric comorbidity and suicidal ideation should be assessed in all BDD patients., Competing Interests: Declaration of competing interest Georgina Krebs receives royalites from Elsevier for editorial work. The other authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, a latest version of COVID-19 pandemic is hand overed. A Stochastic post COVID-19 delayed model is developed to explore the spread of COVID-19 as well as omicron variant with the correlation of heart attack. This article provides an eradication of the COVID-19 and omicron variant as well as the population who have heart attack after post COVID-19 of these epidemic diseases. Then the existence and uniqueness of global positive solution are studied. Ensuing, In this article, we classify COVID-19 virus and omicron variant which go to extinction and become persistent in mean. By using Lyapunov function, the existence of ergodic stationary distribution are established. Later from the persistent disease as well as extinction, heart disease are ready to develop in the human body. By Eventually, an optimal control strategies are introduced in the form of stochastic post COVID-19 delayed model to control two different types of virus. Finally, the numerical simulation are presented to determine the behavior of dynamical system by utilizing the real data of United Kingdom., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking., Methods: Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models., Results: We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the "Absence of trauma and psychopathology" cluster, the "adverse childhood experiences (ACEs) with psychopathology" cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 - 1.23] for biological and 1.52 [1.18 - 1.95] for facial aging acceleration), while no such association was observed for the "ACEs without psychopathology" cluster (1.04 [0.99 - 1.09] and 1.02 [0.84 - 1.24]., Conclusions: Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals' psychological resilience to prevent aging acceleration., (© 2024. The Author(s).)

Background: High cognitive reserve (CR) has been related to lower dementia risk, but its association with heart disease (HD) is unknown. We aimed to explore the relation of CR to HD and cardiac structure and function., Methods and Results: Within the UK Biobank, 349 907 HD-free participants were followed up. A composite CR indicator involving education/occupation attainment/television viewing time/confiding frequency/social connection frequency/variety of leisure activities was generated, and further categorized into low/moderate/high levels. Incident HD, including coronary HD, cardiac arrhythmia, and heart failure, was ascertained on the basis of medical records. During the follow-up, a subsample (n=31 182) underwent cardiac magnetic resonance imaging to assess ventricular structure and function. Data were analyzed using Cox regression, Laplace regression, and linear regression. Compared with low CR, the hazard ratio and 95% CI of any HD for high CR was 0.78 (0.75-0.80) (including 0.68 [0.66-0.71] for coronary HD, 0.91 [0.87-0.95] for cardiac arrhythmia, and 0.63 [0.58-0.68] for heart failure). Furthermore, high CR was associated with delayed HD onset by 1.59 (95% CI, 1.37-1.82) years compared with low CR. In cardiac magnetic resonance imaging data analysis, compared with low CR, high CR was associated with larger left ventricular end-diastolic volume (β, 0.13 [95% CI, 0.09-0.17]), left ventricular end-systolic volume (β, 0.05 [95% CI, 0.01-0.10]), left ventricular stroke volume (β, 0.16 [95% CI, 0.12-0.21]), and left ventricular ejection fraction (β, 0.08 [95% CI, 0.03-0.13])., Conclusions: High CR is associated with favorable HD health. Our findings suggest that the beneficial effect of CR is not limited to dementia but also HD.

Background: Both body mass index (BMI) and genetic factors independently contribute to cardiovascular disease (CVD). However, it is unclear whether genetic risk modifies the association between BMI and the risk of incident CVD. This study aimed to investigate whether BMI categories and genetic risk jointly and interactively contribute to incident CVD events, including hypertension (HTN), atrial fibrillation (AF), coronary heart disease (CHD), stroke, and heart failure (HF)., Methods: A total of 496,851 participants from the UK Biobank with one or more new-onset CVD events were included in the analyses. BMI was categorized as normal weight (< 25.0 kg/m 2 ), overweight (25.0-29.9 kg/m 2 ), and obesity (≥ 30.0 kg/m 2 ). Genetic risk for each outcome was defined as low (lowest tertile), intermediate (second tertile), and high (highest tertile) using polygenic risk score. The joint associations of BMI categories and genetic risk with incident CVD were investigated using Cox proportional hazard models. Additionally, additive interactions were evaluated., Results: Among the 496,851 participants, 270,726 (54.5%) were female, with a mean (SD) age was 56.5 (8.1) years. Over a median follow-up (IQR) of 12.4 (11.5-13.1) years, 102,131 (22.9%) participants developed HTN, 26,301 (5.4%) developed AF, 32,222 (6.9%) developed CHD, 10,684 (2.2%) developed stroke, and 13,304 (2.7%) developed HF. Compared with the normal weight with low genetic risk, the obesity with high genetic risk had the highest risk of CVD: HTN (HR: 3.96; 95%CI: 3.84-4.09), AF (HR: 3.60; 95%CI: 3.38-3.83), CHD (HR: 2.76; 95%CI: 2.61-2.91), stroke (HR: 1.44; 95%CI: 1.31-1.57), and HF (HR: 2.47; 95%CI: 2.27-2.69). There were significant additive interactions between BMI categories and genetic risk for HTN, AF, and CHD, with relative excess risk of 0.53 (95%CI: 0.43-0.62), 0.67 (95%CI: 0.51-0.83), and 0.37 (95%CI: 0.25-0.49), respectively., Conclusions: BMI and genetic factors jointly and interactively contribute to incident CVD, especially among participants with high genetic risk. These findings have public health implications for identifying populations more likely to have cardiovascular benefit from weight loss interventions., (© 2024. The Author(s).)

Background: Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex., Methods: A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models., Results: We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (P interaction  < 0.05). Of note, metabolically healthy obesity phenotype contributed to increased risks of most ORC in men (HRs: 1.58 ~ 2.91), but only correlated with higher risks of endometrial (HR = 1.89, 95% CI: 1.54-2.32) and postmenopausal breast cancers (HR = 1.17, 95% CI: 1.05-1.31) in women. Similarly, even under metabolically healthy, men carrying apple and wide shapes phenotypes (metabolically healthy apple/wide and metabolically healthy non-obesity apple/wide) suffered an increased risk of ORC (mainly colorectal, liver, gastric cardia, and renal cancers, HRs: 1.20 ~ 3.81) in comparison with pear shape or non-obesity pear shape., Conclusions: There was a significant sex disparity between metabolic-anthropometric phenotypes and ORC risk. We advised future ORC prevention and control worth taking body shape and sex disparity into account., (© 2024. The Author(s).)

Identifying people at risk for progressive chronic kidney disease and connecting them with recommended care is crucial for providing timely and optimal treatment. The ASSIST-CKD (A programme to Spread eGFR [estimated glomerular filtration rate] graph Surveillance for the early identification, Support and Treatment of people with progressive CKD [chronic kidney disease]) trial evaluated the effect of graphical eGFR reporting to primary care physicians on late presentation to a nephrologist in the United Kingdom. Trial data were obtained from the UK Renal Registry. Although the results were neutral, the data generated from the ASSIST-CKD trial are informative and provide useful estimates of the intervention effect. The trial also provides valuable insights into the challenges of implementing complex interventions in busy health care environments, which can be used to guide the designs of future interventions., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

During 2020-2022, players and staff in the English Premier League in the United Kingdom were tested regularly for SARS-CoV-2 with the aim of creating a biosecure bubble for each team. We found that prevalence and reinfection estimates were consistent with those from other studies and with community infection trends.

Background: The emergence of long COVID as a COVID-19 sequela was largely syndromic in characterisation. Digital health technologies such as wearable devices open the possibility to study this condition with passive, objective data in addition to self-reported symptoms. We aimed to quantify the prevalence and severity of symptoms across collected mobile health metrics over 12 weeks following COVID-19 diagnosis and to identify risk factors for the development of post-COVID-19 condition (also known as long COVID)., Methods: The Covid Collab study was a longitudinal, self-enrolled, community, case-control study. We recruited participants from the UK through a smartphone app, media publications, and promotion within the Fitbit app between Aug 28, 2020, and May 31, 2021. Adults (aged ≥18 years) who reported a COVID-19 diagnosis with a positive antigen or PCR test before Feb 1, 2022, were eligible for inclusion. We compared a cohort of 1200 patients who tested positive for COVID-19 with a cohort of 3600 sex-matched and age-matched controls without a COVID-19 diagnosis. Participants could provide information on COVID-19 symptoms and mental health through self-reported questionnaires (active data) and commercial wearable fitness devices (passive data). Data were compared between cohorts at three periods following diagnosis: acute COVID-19 (0-4 weeks), ongoing COVID-19 (4-12 weeks), and post-COVID-19 (12-16 weeks). We assessed sociodemographic and mobile health risk factors for the development of long COVID (defined as either a persistent change in a physiological signal or self-reported symptoms for ≥12 weeks after COVID-19 diagnosis)., Findings: By Aug 1, 2022, 17 667 participants had enrolled into the study, of whom 1200 (6·8%) cases and 3600 (20·4%) controls were included in the analyses. Compared with baseline (65 beats per min), resting heart rate increased significantly during the acute (0·47 beats per min; odds ratio [OR] 1·06 [95% CI 1·03-1·09]; p<0·0001), ongoing (0·99 beats per min; 1·11 [1·08-1·14]; p<0·0001), and post-COVID-19 (0·52 beats per min; 1·04 [1·02-1·07]; p=0·0017) phases. An increased level of historical activity in the period from 24 months to 6 months preceding COVID-19 diagnosis was protective against long COVID (coefficient -0·017 [95% CI -0·030 to -0·003]; p=0·015). Depressive symptoms were persistently elevated following COVID-19 (OR 1·03 [95% CI 1·01-1·06]; p=0·0033) and were a potential risk factor for developing long COVID (1·14 [1·07-1·22]; p<0·0001)., Interpretation: Mobile health technologies and commercial wearable devices might prove to be a useful resource for tracking recovery from COVID-19 and the prevalence of its long-term sequelae, as well as representing an abundant source of historical data. Mental wellbeing can be impacted negatively for an extended period following COVID-19., Funding: National Institute for Health and Care Research (NIHR), NIHR Maudsley Biomedical Research Centre, UK Research and Innovation, and Medical Research Council., Competing Interests: Declaration of interests AAF reports shares in Google, the parent company of Fitbit, which produces the wearable devices used in the study to collect data. No funding or devices were provided by Google or Fitbit, but Fitbit advertised the study in the UK Fitbit app. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: This study aims to prospectively examine the association between temperatures and the occurrence of type 2 diabetes (T2D)., Methods: We used the CPH models to analyze 103,215 non-diabetic participants in the UK Biobank cohort who answered questions about workplace temperature, to evaluate the survival relationship, and the interaction effects of working environmental temperature and T2D-related genetic risk scores (GRS) on the occurrence of T2D. The occurrence of T2D was assessed by hospital inpatient records. The weighted T2D-related GRS were calculated., Results: During 1,355,200.6 person-years follow-up, a total of 2436 participants were documented as having diagnosed T2D. After adjustment, compared to the comfortable group, the participants working in non-comfortable environmental temperature had greater risk of T2D (HR: 1.27, 95 %CI: 1.04 to 1.55, for cold; HR: 1.32, 95 %CI: 1.17 to 1.48 for hot; HR: 1.51, 95 %CI: 1.38 to 1.65 for alternate). Similarly, individuals exposed to different levels of genetic risk scores in alternating hot and cold work environments had a higher risk of developing type 2 diabetes., Conclusions: This study found working in single non-comfortable environmental temperatures was associated with greater risk of T2D occurrence, and exposure to alternating environmental temperatures had the highest risk of range and severity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning., Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK. In the C-Fog study, a subset of PHOSP-COVID participants who consented to be recontacted for other research were invited to complete a computerised cognitive assessment and clinical scales between 2 years and 3 years after hospital admission. Participants completed eight cognitive tasks, covering eight cognitive domains, from the Cognitron battery, in addition to the 9-item Patient Health Questionnaire for depression, the Generalised Anxiety Disorder 7-item scale, the Functional Assessment of Chronic Illness Therapy Fatigue Scale, and the 20-item Cognitive Change Index (CCI-20) questionnaire to assess subjective cognitive decline. We evaluated how the absolute risks of symptoms evolved between follow-ups at 6 months, 12 months, and 2-3 years, and whether symptoms at 2-3 years were predicted by earlier aspects of COVID-19 illness. Participants completed an occupation change questionnaire to establish whether their occupation or working status had changed and, if so, why. We assessed which symptoms at 2-3 years were associated with occupation change. People with lived experience were involved in the study., Findings: 2469 PHOSP-COVID participants were invited to participate in the C-Fog study, and 475 participants (191 [40·2%] females and 284 [59·8%] males; mean age 58·26 [SD 11·13] years) who were discharged from one of 83 hospitals provided data at the 2-3-year follow-up. Participants had worse cognitive scores than would be expected on the basis of their sociodemographic characteristics across all cognitive domains tested (average score 0·71 SD below the mean [IQR 0·16-1·04]; p<0·0001). Most participants reported at least mild depression (263 [74·5%] of 353), anxiety (189 [53·5%] of 353), fatigue (220 [62·3%] of 353), or subjective cognitive decline (184 [52·1%] of 353), and more than a fifth reported severe depression (79 [22·4%] of 353), fatigue (87 [24·6%] of 353), or subjective cognitive decline (88 [24·9%] of 353). Depression, anxiety, and fatigue were worse at 2-3 years than at 6 months or 12 months, with evidence of both worsening of existing symptoms and emergence of new symptoms. Symptoms at 2-3 years were not predicted by the severity of acute COVID-19 illness, but were strongly predicted by the degree of recovery at 6 months (explaining 35·0-48·8% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); by a biocognitive profile linking acutely raised D-dimer relative to C-reactive protein with subjective cognitive deficits at 6 months (explaining 7·0-17·2% of the variance in anxiety, depression, fatigue, and subjective cognitive decline); and by anxiety, depression, fatigue, and subjective cognitive deficit at 6 months. Objective cognitive deficits at 2-3 years were not predicted by any of the factors tested, except for cognitive deficits at 6 months, explaining 10·6% of their variance. 95 of 353 participants (26·9% [95% CI 22·6-31·8]) reported occupational change, with poor health being the most common reason for this change. Occupation change was strongly and specifically associated with objective cognitive deficits (odds ratio [OR] 1·51 [95% CI 1·04-2·22] for every SD decrease in overall cognitive score) and subjective cognitive decline (OR 1·54 [1·21-1·98] for every point increase in CCI-20)., Interpretation: Psychiatric and cognitive symptoms appear to increase over the first 2-3 years post-hospitalisation due to both worsening of symptoms already present at 6 months and emergence of new symptoms. New symptoms occur mostly in people with other symptoms already present at 6 months. Early identification and management of symptoms might therefore be an effective strategy to prevent later onset of a complex syndrome. Occupation change is common and associated mainly with objective and subjective cognitive deficits. Interventions to promote cognitive recovery or to prevent cognitive decline are therefore needed to limit the functional and economic impacts of COVID-19., Funding: National Institute for Health and Care Research Oxford Health Biomedical Research Centre, Wolfson Foundation, MQ Mental Health Research, MRC-UK Research and Innovation, and National Institute for Health and Care Research., Competing Interests: Declaration of interests AHa is co-director and owner of H2CD, and owner and director of Future Cognition, which support online studies and develop custom cognitive assessment software, respectively. PJHe is director and CEO of H2CD. JDC declares grants from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Gilead Sciences, and Genentech; and consulting fees from AstraZeneca, Boehringer Ingelheim, Insmed, Novartis, Gilead Sciences, Chiesi, Zambon, and Genentech. L-PH declares grants to their institution from UK Research and Innovation (UKRI), Regenerative Medicine Platform, Celgene, British Lung Foundation, and Oxford Boehringer Ingleheim; the author is on the advisory board for the CATALYST trial and acts as chair of the Respiratory Translational Research Collaboration. AHo declares a grant to their institution from UKRI and the UK National Institute for Health Research (NIHR) to complete this work, funding from NIHR Manchester Clinical Research Facility to support study delivery, and personal funding from NIHR Manchester Biomedical Research Centre (BRC). AHo declares institutional payments to support grant-funded research from NIHR, UK Medical Research Council (MRC), Cystic Fibrosis Trust, Cystic Fibrosis Foundation, North West Lung Centre Charity, and Moulton Trust; consulting fees from Mylan Pharmaceuticals for advisory board participation; and payment from Vertex Pharmaceuticals for educational presentation, participation on a clinical trials advisory board, and writing of a review article. AHo's non-paid roles include chair of the Cystic Fibrosis Clinical Trials Accelerator Program, deputy chair of the NIHR Respiratory Translational Research Collaboration, and director of a university spin-out company (Mi-trial). BR declares payments from the British Heart Foundation Oxford Centre of Research Excellence, NIHR Oxford BRC, and UKRI for grants and contracts; and consulting fees from Axcella Therapeutics. ASh, ASi, and MM declare a grant to their institution from UKRI and NIHR to complete this work. ASh declares unremunerated participation on the AstraZeneca Thrombotic Thrombocytopenic Taskforce and Scottish and UK Governments COVID-19 advisory groups. LH-W declares a grant from NIHR unrelated to the submitted work; acting as independent chair of the NIHR Health Technology Assessment Committee for Colour COPD trial; and membership of the American Thoracic Society Pulmonary Rehabilitation Assembly Web and Planning Committees. NIL declares acting as director of research at the Intensive Care Society UK. CEB declares a grant to their institution from UKRI and NIHR to complete this work; the author reports grants from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim, Chiesi, Novartis, Roche, Genentech, Mologic, and 4DPharma; and consultancy fees paid to their institution from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma, and Teva. LVW declares research funding unrelated to the submitted work from GSK and Orion; consulting fees unrelated to the submitted work from Galapagos; a Wellcome Conference speaker honorarium; travel support from Genentech; advisory board participation for Galapagos; and an associate editor role for the European Respiratory Journal. RAE declares a grant to their institution from UKRI and NIHR to complete this work; the author declares speaker fees from Boehringer Ingelheim and unpaid roles as European Respiratory Society Assembly 01·02 Pulmonary Rehabilitation secretary and with the American Thoracic Society Pulmonary Rehabilitation Assembly programme committee. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: The role of circulating polyunsaturated fatty acids (PUFAs) in preventing liver cirrhosis complications remains unclear., Methods: Between 2006 and 2010, 273,834 UK Biobank participants with plasma PUFA quantification data were enrolled and followed up until October 31, 2022. Plasma PUFAs were quantified using a high-throughput nuclear magnetic resonance-based metabolic profiling platform. Liver cirrhosis complications were defined as hospitalization for liver cirrhosis or presentation with hepatocellular carcinoma., Results: During a median follow-up of 13.9 years, 2026 participants developed liver cirrhosis complications. Total plasma PUFAs, omega-3 PUFAs, docosahexaenoic acid (DHA), omega-6 PUFAs, and linoleic acid (LA) were inversely associated with the risk of liver cirrhosis complications, whereas the plasma omega-6/omega-3 ratio was positively associated. Nonparametrically restricted cubic spline regression showed nonlinear associations of plasma PUFAs with liver cirrhosis complications. The inflection points were 4.78 mmol/L for total PUFAs, 0.73 mmol/L for omega-3 PUFAs, 0.25 mmol/L for DHA, 4.07 mmol/L for omega-6 PUFAs, and 2.99 mmol/L for LA. Plasma omega-3 PUFAs were negatively associated with the risk of liver cirrhosis complications when omega-3 PUFAs were <0.73 mmol/L (adjusted hazard ratio [HR], 0.11 [0.08-0.16]), whereas the association was inverted when omega-3 PUFAs were ≥0.73 mmol/L (adjusted HR, 1.87 [1.20-2.92])., Conclusions: The protective effect of plasma omega-3 PUFAs on liver cirrhosis complications is reversed after passing the corresponding inflection point, suggesting an optimal dietary omega-3 PUFA supplementation dose., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic caused global challenges, including the restriction of surgical options for women with breast cancer. Autologous reconstruction availability has still not returned to pre-COVID-19 levels. This study aimed to collect data about waiting lists for autologous breast reconstruction and is the first of its kind. A total of 31 units were approached and asked to complete a study specific questionnaire. In total, there are at least 2255 patients on a waiting list, which equates to a 2-year and 5-month backlog at the current level of provision, without the inclusion of new referrals. Alarmingly, 40 women reportedly developed breast cancer whilst on the waiting list. The impact of COVID-19 has been significant, revealing national inequity in reconstruction provision and long waiting lists. Recommendations include increasing theatre capacity, optimising plastic surgeons' job plans to prevent waiting lists from growing as well as training more surgeons in autologous reconstruction., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Background: The associations of physical pre-frailty and frailty with bone fractures and the modified effect of sedentary lifestyle remain uncertain. This study was performed to explore the association of physical pre-frailty and frailty with risk of incident bone fractures, and test the modification effects of sedentary lifestyle and other risk factors., Methods: This cohort study included 413 630 participants without bone fractures at baseline in the UK Biobank study between 2006 and 2010 and followed up to 2021. The mean age of the participants was 56.5 years. A total of 224 351 (54.2%) enrolled participants were female and 376 053 (90.9%) included participants were White. Three Cox regression models were constructed to analyze the association of pre-frailty and frailty with total fractures, hip fractures, vertebrae fractures, and other fractures., Results: As compared with the physical nonfrailty group, the multivariate-adjusted hazard ratios were 1.17 (95% confidence interval [CI]: 1.14-1.21) and 1.63 (95% CI: 1.53-1.74) for the physical pre-frailty group and frailty group, respectively (p-trend < .001). In addition, we found that sedentary behavior time significantly accentuated the associations of physical pre-frailty and frailty with total fractures (p-interaction <.001), hip fractures (p-interaction = .013), and other fractures (p-interaction <.001)., Conclusions: Our results indicate that physical pre-frailty and frailty are related to higher risks of bone fractures; such association was more pronounced among those with longer sedentary behavior time., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Background: Metabolic dysfunction-associated fatty liver disease is a significant risk factor for cardiovascular disease (CVD). This study assesses the association between leisure-time physical activity, sedentary behavior, and CVD risk among patients with metabolic dysfunction-associated fatty liver disease, considering genetic predisposition to CVD., Methods: This cohort study included 157 794 participants with metabolic dysfunction-associated fatty liver disease from the UK Biobank who were free of CVD at baseline. The study measured leisure-time sedentary behaviors (watching TV, using a computer, and driving) and physical activities (walking for pleasure, light and heavy do-it-yourself activities, strenuous sports, and other exercises) in terms of frequency and duration over the 4 weeks before assessment. Both a Cox proportional hazard model and an isotemporal substitution model were utilized in the study to assess the association between leisure sedentary behavior, physical activities, and CVD risk., Results: During a median 12.5 years of follow-up, 26 355 CVD cases were reported, including 19 746 coronary heart disease, 4836 stroke, and 7398 heart failure cases. High physical activity levels were linked to a significantly lower risk of CVD (21%), coronary heart disease (20%), stroke (15%), and heart failure (31%). In contrast, individuals with >6.5 h/d of sedentary behavior faced a 16% to 21% higher risk of these conditions compared with those with ≤3.5 h/d. Notably, replacing 30 minutes of inactivity with physical activity reduced CVD risks by 3% to 16%, particularly with strenuous sports. A significant interaction was observed between physical activity, sedentary behavior, and genetic predisposition in relation to stroke risk., Conclusions: Among patients with metabolic dysfunction-associated fatty liver disease, higher leisure-time physical activity levels correlate with reduced CVD risks, while increased sedentary behavior is linked to higher CVD risks. Replacing sedentary time with physical activity consistently shows benefits in reducing CVD outcomes, irrespective of genetic predisposition., Competing Interests: None.

We examined the relationship between genetic risk for schizophrenia (SZ), using polygenic risk scores (PRSs), and retinal morphological alterations. Retinal structural and vascular indices derived from optical coherence tomography (OCT) and color fundus photography (CFP) and PRSs for SZ were analyzed in N = 35,024 individuals from the prospective cohort study, United Kingdom Biobank (UKB). Results indicated that macular ganglion cell-inner plexiform layer (mGC-IPL) thickness was significantly inversely related to PRS for SZ, and this relationship was strongest within higher PRS quintiles and independent of potential confounders and age. PRS, however, was unrelated to retinal vascular characteristics, with the exception of venular tortuosity, and other retinal structural indices (macular retinal nerve fiber layer [mRNFL], inner nuclear layer [INL], cup-to-disc ratio [CDR]). Additionally, the association between greater PRS and reduced mGC-IPL thickness was only significant for participants in the 40-49 and 50-59 age groups, not those in the 60-69 age group. These findings suggest that mGC-IPL thinning is associated with a genetic predisposition to SZ and may reflect neurodevelopmental and/or neurodegenerative processes inherent to SZ. Retinal microvasculature alterations, however, may be secondary consequences of SZ and do not appear to be associated with a genetic predisposition to SZ., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven M. Silverstein reports financial support was provided by Empire State Development. Kelsey V. Stuart reports financial support was provided by Fight for Sight. Pearse A. Keane reports financial support was provided by UK Research and Innovation Future Leaders Fellowship. Pearse A. Keane reports financial support was provided by NIHR Moorfields Biomedical Research Centre. Pearse A. Keane reports financial support was provided by University College London Institute of Ophthalmology. Anthony P. Khawaja reports financial support was provided by UK Research and Innovation Future Leaders Fellowship. Anthony P. Khawaja reports financial support was provided by Alcon Research Institute. Anthony P. Khawaja reports financial support was provided by Lister Institute of Preventive Medicine. Anthony P. Khawaja reports financial support was provided by NIHR Moorfields Biomedical Research Centre. Anthony P. Khawaja reports financial support was provided by University College London Institute of Ophthalmology. Siegfried K. Wagner reports financial support was provided by Medical Research Council Clinical Research Training Fellowship. Brittany A. Blose declares that she has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: We examined whether gender identity and sexual orientation were associated with seven health-related behaviours, and with co-occurrence and clustering of these behaviours among British adolescents., Methods: Millennium Cohort Study (age 17 wave) provided data on the exposures, gender identity (male, female, genderqueer) and sexual orientation (heterosexual, bisexual, gay or lesbian, or other), and seven self-reported health-related behaviours (binge drinking, drug use, no consumption of breakfast, no consumption of fruits or vegetables, physical inactivity, poor sleep, and smoking or vaping). Poisson regressions examined associations between the exposures and single behaviours (reporting prevalence ratios (PRs)); and multinomial logistic regressions were used for behavioural cumulative co-occurrence score (reporting PRs). Cluster patterns were identified using Ward's agglomerative hierarchical cluster analysis while associations with cluster membership were performed using logistic regressions (reporting odds ratios (ORs))., Results: Our sample included 6022 adolescents (55.4% female, 1.5% genderqueer, 11.6% non-heterosexual). Adolescents who identified as genderqueer had the highest prevalence of not eating breakfast (PR: 60.5% [95%CI 48.4-71.4]) and poor sleep (68.7% [95%CI 55.6-79.3]). Those who identified as bisexual had a higher PR of co-occurring behaviours (2.46 [95%CI 1.39-4.27]). Among the three clusters identified (1: Multiple risk behaviours; 2: Physical inactivity and binge drinking; 3: Poor diet and physical inactivity), adolescents who identified as genderqueer or other sexual orientation showed the highest prevalence in cluster 3., Conclusion: Gender and sexual minority British adolescents showed a higher prevalence of risky health-related behaviours, and higher risk of co-occurring behaviours. Physical inactivity and poor diet behaviours commonly clustered together for these groups., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: People with immune-mediated inflammatory disease are at increased risk of pneumococcal pneumonia. The effectiveness of pneumococcal vaccination in people with immune-mediated inflammatory diseases has not been evaluated. We investigated the effectiveness of pneumococcal vaccination in preventing morbidity and mortality associated with pneumonia in patients with immune-mediated inflammatory diseases., Methods: In this matched case-control study, we used primary-care electronic health record data from the Clinical Practice Research Datalink Gold database in the UK, with linked hospitalisation and mortality data. Adults with incident common immune-mediated inflammatory diseases diagnosed between April 1, 1997, and Dec 31, 2019, were followed up from the first diagnosis date to the occurrence of an outcome or date of last follow-up. Cases (ie, those with an outcome of interest) were age-matched and sex-matched to up to ten contemporaneous controls by use of incidence density sampling. Outcomes were hospitalisation due to pneumonia, death due to pneumonia, or primary-care consultation for lower respiratory tract infection requiring antibiotics. We defined hospital admission for pneumonia using hospital discharge diagnoses, death due to pneumonia using death certification data, and lower respiratory tract infection as present when primary-care consultation and antibiotic prescription occurred on the same date. We used multivariable, unconditional, logistical regression and constructed three models to examine the association between pneumococcal vaccination as an exposure and each of the three outcomes., Findings: The first nested case-control analysis included 12 360 patients (7326 [59·3%] women and 5034 [40·7%] men): 1884 (15·2%) who were hospitalised due to pneumonia and 10 476 (84·8%) who were not admitted to hospital due to pneumonia. The second analysis included 5321 patients (3112 [58·5%] women and 2209 [41·5%] men): 781 (14·7%) who died due to pneumonia and 4540 (85·3%) who were alive on the index date. The third analysis included 54 530 patients (33 605 [61·6%] women and 20 925 [38·4%] men): 10 549 (19·3%) with lower respiratory tract infection treated with antibiotics and 43 981 (80·7%) without infection. In the multivariable analysis, pneumococcal vaccination was negatively associated with hospitalisation due to pneumonia (adjusted odds ratio 0·70 [95% CI 0·60-0·81]), death due to pneumonia (0·60 [0·48-0·76]), and lower respiratory tract infection treated with antibiotics (0·76 [0·72-0·80])., Interpretation: Pneumococcal vaccination is associated with protection against hospitalisation and death due to pneumonia in patients with immune-mediated inflammatory diseases, without apparent residual confounding. However, residual unmeasured confounding cannot be fully excluded in observational research, which includes nested case-control studies. These findings should also be corroborated with data from other countries, given that this study used UK-based data., Funding: National Institute for Health and Care Research., Competing Interests: Declaration of interests AA reports personal fees from UpToDate (royalty), Cadilla Pharmaceuticals (lecture fees), and Limbic (consulting), unrelated to this work. CDM is Director of the National Institute for Health and Care Research (NIHR) School for Primary Care Research. Keele University has received research funding for CDM from the NIHR and the Medical Research Council. JSNV-T was seconded to the UK Department of Health and Social Care from October, 2017, to March, 2022. He performed a one-off consultancy for MSD, which manufactures PPV23, in May, 2023. All other authors declare no competing interests. The views expressed in this manuscript are those of its authors and not necessarily those of the NIHR, the Department of Health and Social Care, or any other entity mentioned above., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating underlying mechanisms may shed light on disease mechanisms. In this study, we aimed to identify (1) epidemiological and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE., Methods: We used metabolomic data from 95 402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Cox proportional-hazards models estimated the associations of 249 metabolites with incident disease. Bidirectional 2-sample Mendelian randomization (MR) estimated the causal effects between metabolites and outcomes using genome-wide association summary statistics for metabolites (n=118 466 from the UK Biobank), CAD (n=184 305 from CARDIoGRAMplusC4D 2015), PAD (n=243 060 from the Million Veterans Project), and VTE (n=650 119 from the Million Veterans Project). Multivariable MR was performed in subsequent analyses., Results: We found that 196, 115, and 74 metabolites were associated ( P <0.001) with CAD, PAD, and VTE, respectively. Further interrogation of these metabolites with MR revealed 94, 34, and 9 metabolites with potentially causal effects on CAD, PAD, and VTE, respectively. There were 21 metabolites common to CAD and PAD and 4 common to PAD and VTE. Many putatively causal metabolites included lipoprotein traits with heterogeneity across different sizes and lipid subfractions. Small VLDL (very-low-density lipoprotein) particles increased the risk for CAD while large VLDL particles decreased the risk for VTE. We identified opposing directions of CAD and PAD effects for cholesterol and triglyceride concentrations within HDLs (high-density lipoproteins). Subsequent sensitivity analyses including multivariable MR revealed several metabolites with robust, potentially causal effects of VLDL particles on CAD., Conclusions: While common vascular conditions are associated with overlapping metabolomic profiles, MR prioritized the role of specific lipoprotein species for potential pharmacological targets to maximize benefits in both arterial and venous beds., Competing Interests: P. Natarajan reports research grants from Allelica, Amgen, Apple, Boston Scientific, Genentech/Roche, and Novartis; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Creative Education Concepts, CRISPR Therapeutics, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, Merck, and Novartis; scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio; being a scientific cofounder of TenSixteen Bio; equity in MyOme, Preciseli, and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. The other authors report no conflicts.

Background: Flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality; however, uncertainty exists about the duration of protection and differences by sex and age. We assessed effects of once-only flexible sigmoidoscopy screening after 21 years' follow-up., Methods: The UK Flexible Sigmoidoscopy Screening Trial is a multicentre randomised controlled trial that recruited men and women aged 55-64 years from general practices serving 14 hospitals. Among participants indicating that they would attend flexible sigmoidoscopy screening if invited, randomisation (2:1) to the control (no further contact) or intervention (invited to once-only flexible sigmoidoscopy screening) group was performed centrally in blocks of 12, stratified by centre, general practice, and household type. Masking of intervention was infeasible. Primary outcomes were colorectal cancer incidence and mortality. The Kaplan-Meier method estimated cumulative incidence. Primary analyses estimated intention-to-treat hazard ratios (HRs) and risk differences, overall and stratified by subsite, sex, and age. The trial is registered with ISRCTN, number 28352761., Findings: Among participants recruited between Nov 14, 1994, and March 30, 1999, 170 432 were eligible and 113 195 were randomly assigned to the control group and 57 237 were randomly assigned to the intervention group. 406 participants were excluded from analyses (268 in the control group and 138 in the intervention group), leaving 112 927 participants in the control group (55 336 [49%] men and 57 591 [51%] women) and 57 099 in the intervention group (27 966 [49%] men and 29 103 [51%] women). Of participants who were invited to be screened, 40 624 (71%) attended screening. Median follow-up was 21·3 years (IQR 18·0-22·2). In the invited-to-screening group, colorectal cancer incidence was reduced compared with the control group (1631 vs 4201 cases; cumulative incidence at 21 years was 3·18% [95% CI 3·03 to 3·34] vs 4·16% [4·04 to 4·29]; HR 0·76 [95% CI 0·72 to 0·81]) with 47 fewer cases per 100 000 person-years (95% CI -56 to -37). Colorectal cancer mortality was also reduced in the invited-to-screening group compared with the control group (502 vs 1329 deaths; cumulative incidence at 21 years was 0·97% [0·88 to 1·06] vs 1·33% [1·26 to 1·40]; HR 0·75 [0·67 to 0·83]) with 16 fewer deaths per 100 000 person-years (-21 to -11). Effects were particularly evident in the distal colorectum (726 incident cancer cases in the invited-to-screening group vs 2434 cases in the control group; HR 0·59 [0·54 to 0·64]; 47 fewer cases per 100 000 person-years [-54 to -41]; 196 cancer deaths in the invited-to-screening group vs 708 deaths in the control group; HR 0·55 [0·47 to 0·64]; 15 fewer deaths per 100 000 person-years [-19 to -12]) and not the proximal colon (871 incident cancer cases in the invited-to-screening group vs 1749 cases in the control group; HR 0·98 [0·91 to 1·07]; one fewer case per 100 000 person-years [-8 to 5]; 277 cancer deaths in the invited-to-screening group vs 547 deaths in the control group; HR 1·00 [0·86 to 1·15]; zero fewer deaths per 100 000 person-years [-4 to 4]). The HR for colorectal cancer incidence was lower in men (0·70 [0·65-0·76]) than women (0·86 [0·79 to 0·93]; p interaction =0·0007) but there was no difference by age., Interpretation: We show that once-only flexible sigmoidoscopy screening reduces colorectal cancer incidence and mortality for two decades and provide important data to inform colorectal cancer screening guidelines., Funding: National Institute for Health and Care Research Health Technology Assessment Programme and the Medical Research Council., Competing Interests: Declaration of interests AJC was the recipient as principal investigator of the current funding from the National Institute for Health and Care Research Health Technology Assessment Programme and from Cancer Research UK. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We aimed to investigate the associations of individual and area-level socioeconomic status (SES) with incident cardiovascular diseases (CVD) alone, cancer alone, and comorbid CVD and cancer, and the mediation role of cardiovascular health score in these associations., Study Design: This was a population-based prospective cohort study., Methods: We used data from the UK Biobank, a population-based prospective cohort study. Latent class analysis was used to create an individual-level SES index based on three indicators (household income, education level, and employment status), and the Townsend Index was defined as the area-level socioeconomic status. We used the American Heart Association's (AHA) Life's Simple 7 (smoking, body weight, physical activity, diet, blood pressure, blood glucose, and total cholesterol) to calculate the cardiovascular health score. We used Cox proportional hazard regression models to estimate the hazard ratio (HR) and 95% confidence interval (CI) adjusted for demographic, environmental, and genetic factors., Results: Compared with high SES, the HRs in participants with low individual and area-level SES were 1.33 (95% confidence interval [CI] 1.29 to 1.38) and 1.24 (95% CI 1.20 to 1.29) for incident CVD, 0.96 (95% CI 0.93 to 0.99) and 0.95 (95%CI 0.92 to 0.98) for incident cancer, 1.32 (95%CI 1.24 to 1.40) and 1.15 (95%CI 1.08 to 1.22) for incident comorbid CVD and cancer, respectively. Additionally, the mediation proportion of CVD score for individual and area-level SES was 47.93% and 48.87% for incident CVD, 44.83% and 59.93% for incident comorbid CVD and cancer. The interactions between individual-level SES and CVD scores were significant on incident CVD, and comorbid CVD and cancer, and the protective associations were stronger in participants with high individual-level SES., Conclusions: Life's Simple 7 significantly mediated the associations between SES and comorbid CVD and cancer, while almost half of the associations remained unclear., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate the association between irregular sleep duration and incident diabetes in a U.K. population over 7 years of follow-up., Research Design and Methods: Among 84,421 UK Biobank participants (mean age 62 years) who were free of diabetes at the time of providing accelerometer data in 2013-2015 and prospectively followed until May 2022, sleep duration variability was quantified by the within-person SD of 7-night accelerometer-measured sleep duration. We used Cox proportional hazard models to estimate hazard ratios (HRs) for incident diabetes (identified from medical records, death register, and/or self-reported diagnosis) according to categories of sleep duration SD., Results: There were 2,058 incident diabetes cases over 622,080 person-years of follow-up. Compared with sleep duration SD ≤ 30 min, the HR (95% CI) was 1.15 (0.99, 1.33) for 31-45 min, 1.28 (1.10, 1.48) for 46-60 min, 1.54 (1.32, 1.80) for 61-90 min, and 1.59 (1.33, 1.90) for ≥91 min, after adjusting for age, sex, and race. We found a nonlinear relationship (P nonlinearity 0.0002), with individuals with a sleep duration SD of >60 vs. ≤60 min having 34% higher diabetes risk (95% CI 1.22, 1.47). Further adjustment for lifestyle, comorbidities, environmental factors, and adiposity attenuated the association (HR comparing sleep duration SD of >60 vs. ≤60 min: 1.11; 95% CI 1.01, 1.22). The association was stronger among individuals with lower diabetes polygenic risk score (PRS; P interaction ≤ 0.0264) and longer sleep duration (P interaction ≤ 0.0009)., Conclusions: Irregular sleep duration was associated with higher diabetes risk, particularly in individuals with a lower diabetes PRS and longer sleep duration., (© 2024 by the American Diabetes Association.)

Objective: This study aimed to understand the effect of time to remission of acromegaly on survival in people living with acromegaly., Design, Patients and Measurement: This cross-sectional study used data from the UK Acromegaly Register. We considered remission of acromegaly growth hormone controlled at ≤2 μg/L following the diagnosis of acromegaly. We used the accelerated failure time model to assess the effect of time to remission on survival in acromegaly., Results: The study population comprises 3569 individuals with acromegaly, with a median age of diagnosis of 47.3 (36.5-57.8) years, 48% females and a majority white population (61%). The number of individuals with the first remission of acromegaly was 2472, and the median time to first remission was 1.92 (0.70-6.58) years. In this study, time to first remission in acromegaly was found to have a significant effect on survival (p < .001); for every 1-year increase in time to first remission, there was a median 1% reduction in survival in acromegaly. In an analysis adjusted for covariates, the survival rate was 52% higher (p < .001) in those who underwent surgery as compared to those who did not have surgery, 18% higher (p = .01) in those who received treatment with somatostatin analogues (SMA) as compared to those with dopamine agonists and 21% lower (p < .001) in those who received conventional radiotherapy as compared to those who did not receive radiotherapy., Conclusion: In conclusion, this population-based study conducted in patients with acromegaly revealed that faster remission time, surgical intervention and treatment with SMA are linked to improved survival outcomes., (© 2024 John Wiley & Sons Ltd.)

This study utilized UK Biobank data from 144 286 participants and employed whole-genome sequencing (WGS) data and time-to-event data over a 12-year follow-up period to identify susceptibility in genetic variants associated with hypertension. Following genotype quality control, 6 319 822 single nucleotide polymorphisms underwent analysis, revealing 31 significant variant-level associations. Among these, 29 were novel - 15 in Fibrillin-2 ( FBN2 ) and 4 in Junctophilin-2 ( JPH2 ). Mendelian randomization utilizing two identified variants (rs17677724 and rs1014754) suggested that a genetically induced decrease in heart FBN2 expression and an increase in adrenal gland JPH2 expression were causally linked to hypertension. Phenome-wide association (PheWAS) analysis using the FinnGen dataset confirmed positive associations of rs17677724 and rs1014754 with hypertension, assessed across 2727 traits in 377 277 individuals. Lastly, rs1014754 positively associated with kallistatin, whereas rs17677724 negatively associated with renin in the Fenland study, suggesting a counterregulatory response to high blood pressure. This study, employing WGS data, identified novel genetic loci and potential therapeutic targets for hypertension., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Chronic pain is associated with development of cardiovascular disease. We investigated the association between how widespread chronic pain is and the development of cardiovascular dysfunction., Methods: We analysed data from participants enrolled in the UK Biobank study who underwent examinations at baseline, plus first follow-up and two imaging visits. Pain sites (including hip, knee, back, neck/shoulder, or 'all over the body') and pain duration were recorded at each visit. Chronic pain was defined as pain lasting for ≥3 months. Participants were categorised into six groups: no chronic pain, chronic pain in one, two, three, or four sites, or 'all over the body'. Arterial stiffness index was measured at each time point. Carotid intima-media thickness, cardiac index, and left ventricular ejection fraction (LVEF) were measured using ultrasound and heart MRI at two additional imaging visits in a subset of participants. Mixed-effect linear regression models were used for the analyses., Results: The number of chronic pain sites was directly related to increased arterial stiffness index (n=159,360; β=0.06 per one site increase, 95% confidence interval 0.04 to 0.08). In 23,899 participants, lower LVEF was associated with widespread chronic pain (β=-0.17 per one site increase, 95% confidence interval -0.27 to -0.07). The number of chronic pain sites was not associated with carotid intima-media thickness (n=30,628) or cardiac index (n=23,899)., Conclusion: A greater number of chronic pain sites is associated with increased arterial stiffness and poorer cardiac function, suggesting that widespread chronic pain is an important contributor to cardiovascular dysfunction., (Copyright © 2024 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Lithium is considered to be the most effective mood stabilizer for bipolar disorder. Evolving evidence suggested lithium can also regulate bone metabolism which may reduce the risk of fractures. While there are concerns about fractures for antipsychotics and mood stabilizing antiepileptics, very little is known about the overall risk of fractures associated with specific treatments. This study aimed to compare the risk of fractures in patients with bipolar disorder prescribed lithium, antipsychotics or mood stabilizing antiepileptics (valproate, lamotrigine, carbamazepine). Among 40,697 patients with bipolar disorder from 1993 to 2019 identified from a primary care electronic health record database in the UK, 13,385 were new users of mood stabilizing agents (lithium:2339; non-lithium: 11,046). Lithium was associated with a lower risk of fractures compared with non-lithium treatments (HR 0.66, 95 % CI 0.44-0.98). The results were similar when comparing lithium with prolactin raising and sparing antipsychotics, and individual antiepileptics. Lithium use may lower fracture risk, a benefit that is particularly relevant for patients with serious mental illness who are more prone to falls due to their behaviors. Our findings could help inform better treatment decisions for bipolar disorder, and lithium's potential to prevent fractures should be considered for patients at high risk of fractures., Competing Interests: Declaration of competing interest Esther W. Chan has received grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Novartis, Amgen, AstraZeneca, Takeda, the RGA Reinsurance Company, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, the National Health and Medical Research Council Australia; consulting fees from AstraZeneca, Pfizer and Novartis; and honorarium from the Hospital Authority Hong Kong, outside the submitted work. Joseph F. Hayes has received consultancy fees from Wellcome Trust and juli Health. Kenneth K.C. Man received the CW Maplethorpe Fellowship, grants from the National Institute for Health Research (United Kingdom), the European Union Horizon 2020 Framework, Innovation and Technology Commission of the Hong Kong Special Administration Region Government, and Hong Kong Research Grant Council and personal fees from IQVIA Holdings, Inc., unrelated to this work. Ian C.K.Wong received research grants from Amgen, Janssen, GSK, Novartis, Pfizer, Bayer and Bristol-Myers Squibb and Takeda, Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, The European Union's Seventh Framework Programme for research, technological development, Research Grants Council Hong Kong and Health and Medical Research Fund Hong Kong; consulting fee from IQVIA and WHO; payment for expert testimony for Appeal Court in Hong Kong; serves on advisory committees for Member of Pharmacy and Poisons Board; Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization; Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government; is the non-executive director of Jacobson Medical in Hong Kong; is the Founder and Director of Therakind Limited (UK), Advance Data Analytics for Medical Science (ADAMS) Limited (HK), Asia Medicine Regulatory Affairs (AMERA) Services Limited and OCUS Innovation Limited (HK, Ireland and UK). Ching-Lung Cheung received research grants and the honorarium from Amgen, research grant support from HMRF, and the honorarium from Abbott. Wallis C.Y. Lau reports grant from Diabetes UK, AIR@InnoHK administered by Innovation and Technology Commission, outside the submitted work. Vanessa W.S. Ng, Miriam T.Y. Leung, and David P.J. Osborn declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diet has been repeatedly shown to affect mental and sleep health outcomes. However, it is well known that there are cross-cultural differences in dietary practices as well as the prevalence of mental and sleep health outcomes. Given that the dietary inflammatory potential of diets has been linked to mental and sleep health outcomes, in the current study we sought to assess the inflammatory status of habitual diets and examine its relationship with mental and sleep health outcomes in both the United Kingdom and Japan. Our aim was to determine if the associations between the dietary inflammation index (DII) score and these health outcomes could elucidate any potential cross-cultural differences in health. Online survey data was collected from 602 participants (aged 18-40 years) in the United Kingdom (n = 288) and Japan (n = 314). Participants self-reported their dietary intakes, as well as current mental health and sleep patterns. The DII score was calculated (score range - 2.79 to 3.49) We found that although participants in the United Kingdom reported better overall mental wellbeing, participants in Japan reported less severe depression, anxiety and stress and better subjective sleep quality, less sleep disturbances and daytime dysfunction, despite sleeping shorter, and a better adherence to an anti-inflammatory diet. Moreover, across the United Kingdom and Japan, adherence to more anti-inflammatory diets predicted higher levels of subjective sleep quality, fewer sleep disturbances, less use of sleep medicine and less daytime dysfunction. In conclusion, there are several differences between mental and sleep health outcomes in the United Kingdom and Japan, which could be attributable to the inflammatory potential of respective regional diets. Future studies are warranted to examine the mental and sleep health benefits of adhering to anti-inflammatory traditional Japanese diets in clinical and subclinical cohorts., (© 2024 The Author(s). Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Objective: To examine associations of surgical and natural menopause before the age of 40 years with the risk of type 2 diabetes (T2D) in women., Methods: A total of 273,331 women from the United Kingdom were recruited between 2006 and 2010 in the UK Biobank (UKB) study, and 146,343 women aged 40 to 69 years who were postmenopausal at baseline were included in the analysis. Surgical menopause and natural premature menopause were defined as bilateral oophorectomy before the age of 40 and menopause before the age of 40 without oophorectomy, respectively. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between premature menopause and the incidence of T2D., Results: During a median follow-up of 10.4 years, 47 women with surgical premature menopause, 244 women with natural premature menopause, and 4724 women without premature menopause developed T2D. Compared with women without premature menopause, both surgical premature menopause (adjusted HR = 1.46, 95 % CI: 1.09-1.95; P = 0.01) and natural premature menopause (adjusted HR = 1.20, 95 % CI: 1.06-1.37; P < 0.01) were associated with higher risks of incident T2D in the multivariable-adjusted models. Additionally, we observed a significant interaction between levels of sex hormone binding globulin (SHBG) (P interaction  < 0.01) and the effects of premature menopause on incident T2D. The association between premature menopause and T2D risk appeared to be stronger in women with higher SHBG levels. Furthermore, a joint association was detected between premature menopause and the genetic risk score (GRS) of T2D, with a higher score indicating a higher risk of developingT2D. The highest risk of T2D was observed with higher T2D GRS and surgical premature menopause (adjusted HR = 2.61, 95 % CI: 1.65-4.12; P < 0.01)., Conclusions: Surgical menopause and natural menopause before the age of 40 years were associated with an increased risk of T2D among postmenopausal women. The findings also suggest potential interactions of premature menopause with SHBG levels, with the association appearing to be stronger in higher SHBG levels, as well as a joint association between menopause status and genetic risk factors on T2D incidence., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Foot complications in diabetes are common and destructive, resulting in substantial healthcare costs and high rates of morbidity. Coastal areas have a significantly higher burden of disease. People with diabetes experience disproportionately high rates of psychological health issues, including anxiety, depression and diabetes distress. These can affect self-management and concordance with preventive measures and treatments of foot complications, negatively impacting on outcomes. Access to psychological health services is variable across the United Kingdom and there is a paucity of high-quality evidence for the effectiveness of treatments for diabetes distress. This study aimed to explore experiences of psychosocial burden and perceptions and experiences of psychosocial support, among patients with diabetes and foot complications living in a coastal area., Methods: Patients were eligible to participate if they had experienced diabetes-related foot complications (amputation, ulceration and/or Charcot neuroarthropathy) within the last 5 years and scored positive for diabetes distress on a validated screening tool (DDS2). Eligible patients completed cross-sectional questionnaires describing symptoms of diabetes distress (DDS17), anxiety (GAD-7) and depression (PHQ-9) and to take part in a face-to-face, semi-structured interview. Questionnaires were analysed using frequencies and interviews were analysed using reflexive thematic analysis., Results: A total of 183 patients completed the DDS2 screening questionnaire. Of these, 56 (30.6%) screened positive for diabetes distress. Twenty-seven patients completed DDS17, GAD-7 and PHQ-9 questionnaires. Eleven (40.7%) participants indicated high levels of diabetes distress and four (14.8%) indicated moderate distress. Seventeen participants (age range 52-81 years; 12 men) took part in an interview. Four key themes were identified: impact of living with foot problems; emotional consequences of foot problems; experiences and perceptions of psychological support; and strategies to cope with the emotional impact of foot problems., Conclusion: Diabetes distress was prevalent among patients with diabetes-related foot complications. Foot problems impacted on participants' daily activities, social lives and ability to work. Despite expressing feelings of ongoing fear, worry and depression relating to their foot problems, only one participant had accessed formal psychological support. Many participants relied on talking to podiatrists at routine appointments and described developing various strategies to cope. The psychosocial burden of living with foot complications in diabetes must not be overlooked by health professionals. Findings from this study can inform the design of future services and interventions., (© 2024 The Author(s). Journal of Foot and Ankle Research published by John Wiley & Sons Australia, Ltd on behalf of Australian Podiatry Association and The Royal College of Podiatry.)

Objectives: Life events can be stressful and have a detrimental impact on health, but evidence is inconclusive regarding life events and dementia risk. The present study tests whether life events are associated with incident dementia, whether experiencing multiple events has cumulative effects, and whether the associations vary across age, sex, race/ethnicity, socioeconomic status, and genetic vulnerability., Methods: UK Biobank participants (N = 493,787) reported on 6 life events that occurred within the past 2 years: serious illness, injury, assault to yourself or close relative, death of a spouse/partner or close relative, marital separation/divorce, and financial problems. Incident all-cause dementia was ascertained through health records from the UK National Health Service over a 16-year follow-up., Results: Serious illness, injury, or assault to yourself, marital separation/divorce, and financial difficulties were associated with a higher risk of dementia; serious illness, injury, or assault of a close relative was associated with a lower risk of dementia. When combined, experiencing 3-4 events was associated with a more than 2-fold increase in dementia risk. The association for marital separation/divorce was stronger within the first 5 years of follow-up (consistent with reverse causality). Death of a spouse/partner or close relative was mostly unrelated to dementia risk. With few exceptions, the associations were similar across age, sex, race/ethnicity, socioeconomic status, and apolipoprotein E e4 status groups., Discussion: Severe illness, injury, or personal assault, marital separation or divorce, and financial hardships may raise risk of dementia, particularly when these events occur together., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Cross-sectional evidence has shown that frailty is highly prevalent in patients with chronic kidney disease (CKD). However, there is limited evidence of the longitudinal associations between frailty, genetic predisposition to CKD, and the risk of CKD in the general population. Therefore, this study aimed to examine such associations among participants in the UK Biobank., Study Design: This is a prospective cohort study included 370,965 middle-aged and older adults from the UK Biobank. Physical frailty was assessed using a modified version of the Fried phenotype classification. A weighted genetic risk score was built using 263 variants associated with estimated glomerular filtration rate., Main Outcome Measures: Incident CKD was identified from hospital inpatient records., Results: Over a median follow-up of 12.3 years, we documented a total of 11,121 incident CKD cases. Time-dependent Cox proportional hazards regression models indicated that individuals with frailty (hazard ratio [HR]: 1.94, 95 % confidence interval [CI]: 1.81-2.08) and pre-frailty (HR: 1.27, 95 % CI: 1.22-1.33) had an increased risk of developing CKD, compared with non-frail individuals. No significant interaction between frailty and genetic risk score was observed (P for interaction = 0.41). The highest risk was observed among the individuals with high genetic risk and frailty (HR: 2.31, 95 % CI: 2.00-2.68)., Conclusion: Our results demonstrated that frailty and pre-frailty were associated with increased risk of incident CKD in middle-age and older adults, regardless of genetic risk of CKD. Our study underscores the importance of frailty screening and intervention as a potential strategy to prevent CKD. Future clinical trials are needed to validate our findings., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The prevalence of mental health issues among UK undergraduate students is growing, and poor diet quality appears to be a risk factor for poor mental health although with limited research in this area. Therefore, the objective of this study was to examine the cross-sectional associations between diet quality and common mental disorders (CMD) such as depression and anxiety in UK undergraduate students. A cross-sectional survey consisting of demographic information and validated questionnaires (the Short-Form Food Frequency Questionnaire [SFFFQ] and the Hospital Anxiety and Depression Scale [HADS]) was conducted to measure diet quality and anxiety and depression in young adults in 44 UK-based universities. Multiple regression analysis adjusting for confounding factors was used to assess the associations between them. Undergraduate university students (n = 202, 67% female) with a mean age of 20.9 ± 3.6 years and a mean body mass index (n = 170) of 22.6 ± 3.2 kg/m 2 took part in the study. Prevalence of anxiety was high, with 40% of the sample having an anxiety score in the severe range (≥12 points) while the prevalence of depression was lower, with 6% of the population having a depression score in the severe range (≥12 points). Diet quality was significantly higher for females than males (p = 0.034) and was poor for 38% of the sample, being more common in males compared to females, although not significantly so (43% and 36%, respectively). Diet quality was inversely associated with anxiety (β = -0.427; p = 0.029) and was more likely to be associated with anxiety in females than males (β = 0.743; p = 0.043). No significant relationship between diet quality and depression was found. Better self-reported health, father's qualification and smoking status were also associated with less anxiety and depression. This research supports other research suggesting that UK universities should explore whether the implementation of dietary interventions and improving the food environment would be a cost-effective option to reduce the high prevalence of anxiety among students., (© 2024 The Author(s). Nutrition Bulletin published by John Wiley & Sons Ltd on behalf of British Nutrition Foundation.)

Purpose: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency., Methods: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels., Results: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40's 12.29 in 50's 12.24 in 60's vs. 10.69 in 40's 10.56 in 50's 10.63 in 60's respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01)., Conclusions: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals' hypogonadal symptoms., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment. Examples are accepting fewer referrals, applying stricter referral criteria and relying more on virtual consultations and multi-disciplinary meetings. Screening service programs paused during the pandemic before enacting risk-based phased restarts with longer appointment times to accommodate reduced staffing numbers and enhanced infection-control regimes. Treatments shifted from predominantly conventional to hypofractionated radiotherapy, fewer surgical procedures and increased use of bridging endocrine therapy. The long-term impact of such changes are unknown so definitive guidelines for future emergencies are not yet available. Cancer registries, with their large sample sizes and population coverage, are well placed to monitor changes to stage and survival despite difficulties obtaining definitive staging during diagnosis because surgery and pathological assessments are delayed. Multisite longitudinal studies can also provide guidance for future disaster preparedness., (© 2024. The Author(s).)

Background: We examined the role of psychological well-being related measures in explaining the associations between obesity and increased risk of non-communicable diseases (NCDs: hypertension, heart disease, stroke, diabetes, arthritis, cancer, and memory-related disease) in older adults., Methods: Data were from the English Longitudinal Study of Ageing (ELSA), UK (baseline: Wave 4-2008/2009; n = 8127) and the Health and Retirement Study (HRS), US (baseline: Waves 9 and 10-2008/2010; n = 12,477). Objective body mass index was used to define obesity. A range of psychological well-being related measures (e.g., depressive symptoms, life satisfaction) was available in ELSA (n = 7) and HRS (n = 15), and an index of overall psychological well-being was developed separately in each study. NCDs were from a self-reported doctor diagnosis and/or other assessments (e.g., biomarker data) in both studies; and in ELSA, NCDs from linked hospital admissions data were examined. Longitudinal associations between obesity status, psychological well-being measures, and NCDs were examined using Cox proportional hazard models (individual NCDs) and Poisson regression (a cumulative number of NCDs). Mediation by psychological well-being related measures was assessed using causal mediation analysis., Results: Obesity was consistently associated with an increased prospective risk of hypertension, heart disease, diabetes, arthritis, and a cumulative number of NCDs in both ELSA and HRS. Worse overall psychological well-being (index measure) and some individual psychological well-being related measures were associated with an increased prospective risk of heart disease, stroke, arthritis, memory-related disease, and a cumulative number of NCDs across studies. Findings from mediation analyses showed that neither the index of overall psychological well-being nor any individual psychological well-being related measures explained (mediated) why obesity increased the risk of developing NCDs in both studies., Conclusion: Obesity and psychological well-being may independently and additively increase the risk of developing NCDs., (© 2024. The Author(s).)

Background: During autumn/winter 2022, UK pediatricians reported an unseasonal increase in invasive group A streptococcal infections; a striking proportion presenting with pneumonia with parapneumonic effusion., Methods: Clinicians across the United Kingdom were requested to submit pseudonymized clinical data using a standardized report form for children (<16 years) admitted between September 30, 2022 and February 17, 2023, with microbiologically confirmed group A streptococcal pneumonia with parapneumonic effusion., Results: From 185 cases submitted, the median patient age was 4.4 years, and 163 (88.1%) were previously healthy. Respiratory viral coinfection was detected on admission for 101/153 (66.0%) children using extended respiratory pathogen polymerase chain reaction panel. Molecular testing was the primary method of detecting group A streptococcus on pleural fluid (86/171; 50.3% samples). Primary surgical management was undertaken in 171 (92.4%) children; 153/171 (89.4%) had pleural drain inserted (96 with fibrinolytic agent), 14/171 (8.2%) had video-assisted thoracoscopic surgery. Fever duration after admission was prolonged (median, 12 days; interquartile range, 9-16). Intravenous antibiotic courses varied in length (median, 14 days; interquartile range, 12-21), with many children receiving multiple broad-spectrum antibiotics, although evidence for additional bacterial infection was limited., Conclusions: Most cases occurred with viral coinfection, a previously well-recognized risk with influenza and varicella zoster, highlighting the need to ensure routine vaccination coverage and progress on vaccines for other common viruses (eg, respiratory syncytial virus, human metapneumovirus) and for group A streptococcus. Molecular testing is valuable to detect viral coinfection and confirm invasive group A streptococcal diagnosis, expediting the incorporation of cases into national reporting systems. Range and duration of intravenous antibiotics administered demonstrated the need for research on the optimal duration of antimicrobials and improved stewardship., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: To investigate factors influencing survival in head and neck squamous cell carcinoma of unknown primary (HNSCCUP)., Methods: A retrospective observational cohort study was conducted, over 5 years from January 2015, in UK Head and Neck centres, of consecutive adults undergoing 18F-Fluorodeoxyglucose-PET-CT within 3 months of diagnosis with metastatic cervical squamous cell carcinoma. Patients treated as HNSCCUP underwent survival analysis, stratified by neck dissection and/or radiotherapy to the ipsilateral neck, and by HPV status., Results: Data were received from 57 centres for 965 patients, of whom 482 started treatment for HNSCCUP (65.7% HPV-positive, n = 282/429). Five-year overall survival (OS) for HPV-positive patients was 85.0% (95% CI 78.4-92.3) and 43.5% (95% CI 32.9-57.5) for HPV-negative. HPV-negative status was associated with worse OS, disease-free (DFS), and disease-specific (DSS) survival (all p < .0001 on log-rank test) but not local control (LC) (p = .16). Unilateral HPV-positive disease treated with surgery alone was associated with significantly worse DFS (p < .0001) and LC (p < .0001) compared to radiotherapy alone or combined modalities (5-year DFS: 24.9%, 82.3% and 94.3%; 5-year LC: 41.8%, 98.8% and 98.6%). OS was not significantly different (p = .16). Unilateral HPV-negative disease treated with surgery alone was associated with significantly worse LC (p = .017) (5-year LC: estimate unavailable, 93.3% and 96.6%, respectively). Small numbers with bilateral disease precluded meaningful sub-group analysis., Conclusions: HPV status is associated with variable management and outcomes in HNSCCUP. Unilateral neck disease is treated variably and associated with poorer outcomes when managed with surgery alone. The impact of diagnostic oropharyngeal surgery on primary site emergence, survival and functional outcomes is unestablished., (© 2024 John Wiley & Sons Ltd.)