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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. [ABSTRACT FROM AUTHOR]

Background: The Ultra-Low Emission Zone (ULEZ), introduced in Central London in April 2019, aims to enhance air quality and improve public health. The Children's Health in London and Luton (CHILL) study evaluates the impact of the ULEZ on children's health. This analysis focuses on the one-year impacts on the shift towards active travel to school. Methods: CHILL is a prospective parallel cohort study of ethnically diverse children, aged 6–9 years attending 84 primary schools within or with catchment areas encompassing London's ULEZ (intervention) and Luton (non-intervention area). Baseline (2018/19) and one-year follow-up (2019/20) data were collected at school visits from 1992 (58%) children who reported their mode of travel to school 'today' (day of assessment). Multilevel logistic regressions were performed to analyse associations between the introduction of the ULEZ and the likelihood of switching from inactive to active travel modes, and vice-versa. Interactions between intervention group status and pre-specified effect modifiers were also explored. Results: Among children who took inactive modes at baseline, 42% of children in London and 20% of children in Luton switched to active modes. For children taking active modes at baseline, 5% of children in London and 21% of children in Luton switched to inactive modes. Relative to the children in Luton, children in London were more likely to have switched from inactive to active modes (OR 3.64, 95% CI 1.21–10.92). Children in the intervention group were also less likely to switch from active to inactive modes (OR 0.11, 0.05–0.24). Moderator analyses showed that children living further from school were more likely to switch from inactive to active modes (OR 6.06,1.87–19.68) compared to those living closer (OR 1.43, 0.27–7.54). Conclusions: Implementation of clean air zones can increase uptake of active travel to school and was particularly associated with more sustainable and active travel in children living further from school. [ABSTRACT FROM AUTHOR]

Background: Encouraging alternatives to the car such as walking, cycling or public transport is a key cross-sector policy priority to promote population and planetary health. Individual travel choices are shaped by individual and environmental contexts, and changes in these contexts – triggered by key events – can translate to changes in travel mode. Understanding how and why these changes happen can help uncover more generalisable findings to inform future intervention research. This study aimed to identify the mechanisms and contexts facilitating changes in travel mode. Methods: Prospective longitudinal qualitative cohort study utilising semi-structured interviews at baseline (in 2021), three- and six-month follow up. Participants were residents in a new town in Cambridgeshire, UK, where design principles to promote walking, cycling and public transport were used at the planning stage. At each interview, we followed a topic guide asking participants about previous and current travel patterns and future intentions. All interviews were audio recorded and transcribed. Data analysis used the framework approach based on realist evaluation principles identifying the context and mechanisms described by participants as leading to travel behaviour change. Results: We conducted 42 interviews with 16 participants and identified six mechanisms for changes in travel mode. These entailed increasing or reducing access, reliability and financial cost, improving convenience, increasing confidence and raising awareness. Participants described that these led to changes in travel mode in contexts where their existing travel mode had been disrupted, particularly in terms of reducing access or reliability or increasing cost, and where there were suitable alternative travel modes for their journey. Experiences of the new travel mode played a role in future travel intentions. Implications: Applying realist evaluation principles to identify common mechanisms for changes in travel mode has the potential to inform future intervention strategies. Future interventions using mechanisms that reduce access to, reduce reliability of, or increase the financial cost of car use may facilitate modal shift to walking, cycling and public transport when implemented in contexts where alternative travel modes are available and acceptable. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the independent and joint associations of accelerometer-derived sleep duration and physical activity (PA) in different intensities with the risk of incident heart failure (HF). The study included 89,572 participants (mean age 62.2 ± 7.8 years, 42.8% male) from the UK Biobank. Sleep duration (short: <6 h/day; normal: 6–8 h/day; long: >8 h/day) and PA [total PA, light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA)] were measured using accelerometers over 7 days. MVPA and VPA were categorized according to the World Health Organization's recommended levels, while LPA and total PA were categorized based on the median. HF cases were identified through hospital records or death registries. Over a 7-year follow-up period, 1324 participants (2.1%; incidence rate, 2.1 per 1000 person-years) developed HF. Short, but not long, sleep duration was linked to a 33% increased risk of HF [hazard ratio (HR) 1.33, 95% confidence interval (CI): 1.11–1.59]. This increased risk associated with short sleep could be mitigated by increasing PA, especially to the levels of recommended MVPA or VPA. In joint analyses, compared to participants meeting the recommended MVPA and with normal sleep duration, those not meeting the MVPA recommendation and with short sleep had the highest HF risk (HR 1.78, 95% CI: 1.42–2.25). Accelerometer-derived short, but not long, sleep duration was associated with a higher risk of incident HF. Engaging in sufficient PA, especially recommended MVPA or VPA, can partially mitigate this risk. [Display omitted] • Accelerometer-measured short sleep duration is independently associated with a higher risk of heart failure. • Higher physical activity levels, regardless of intensity, reduce the heart failure risk linked to short sleep duration. • Our study suggests for promoting recommended levels of PA, especially in situations where sleep duration may be compromised. [ABSTRACT FROM AUTHOR]

To examine associations between regular statin use and the incidence of depression and anxiety. This cohort was based on UK Biobank participants without depression/anxiety recruited between 2006 and 2010. The self-reported regular statin use was collected at baseline. Depression and anxiety outcomes were assessed by diagnostic interviews (international classification of diseases codes) and nondiagnostic scales (mental well-being questionnaires). Cox proportional hazards models adjusted for a wide range of confounders were used to estimate associations of statins with incident depression/anxiety. Among 363,551 eligible participants, 55,838 reported regular statin use. During a 13-year follow-up, 14,765 cases of depression and 15,494 cases of anxiety were identified. Compared with non-statin users, statin use was associated with reduced risk of depression (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81, 0.94) and anxiety (HR: 0.90, 95% CI: 0.84, 0.97). Effects of statins on depression were consistent in sensitivity analyses and may be less influenced by unmeasured confounders. However, results of online survey data showed that statin use might not be associated with incident anxiety (HR: 0.96, 95% CI: 0.85, 1.09). Regular statin use was associated with a lower risk of depression. No clear associations between statin use and anxiety were found. [ABSTRACT FROM AUTHOR]

Purpose: To explore the joint association of dietary patterns and adiposity with colorectal cancer (CRC), and whether adiposity mediates the relationship between dietary patterns and CRC risk, which could provide deeper insights into the underlying pathogenesis of CRC. Methods: The data of 307,023 participants recruited between 2006 and 2010 were extracted from the UK Biobank study. Healthy diet scores were calculated based on self-reported dietary data at baseline, and participants were categorized into three groups, namely, low, intermediate, and high diet score groups. Cox regression models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the effects of the healthy diet score on CRC incidence, adjusting for various covariates. Furthermore, the mediation roles of obesity and central obesity between the healthy diet score and CRC risk were assessed using a counterfactual causal analysis based on Cox regression model. Additionally, joint association between dietary patterns and adiposity on CRC risks was assessed on the additive and multiplicative scales. Results: Over a median 6.2-year follow-up, 3,276 participants developed CRC. After adjusting for sociodemographic and lifestyle factors, a lower risk of CRC incidence was found for participants with intermediate (HR = 0.83, 95% CI: 0.72 to 0.95) and high diet scores (HR = 0.73, 95% CI: 0.62 to 0.87) compared to those with low diet scores. When compared with the low diet score group, obesity accounted for 4.13% and 7.93% of the total CRC effect in the intermediate and high diet score groups, respectively, while central obesity contributed to 3.68% and 10.02% of the total CRC risk in the intermediate and high diet score groups, respectively. The mediating effect of adiposity on CRC risk was significant in men but not in women. Concurrent unhealthy diet and adiposity multiplied CRC risk. Conclusion: Adiposity-mediated effects were limited in the link between dietary patterns and CRC incidence, implying that solely addressing adiposity may not sufficiently reduce CRC risk. Interventions, such as improving dietary quality in people with adiposity or promoting weight control in those with unhealthy eating habits, may provide an effective strategy to reduce CRC risk. [ABSTRACT FROM AUTHOR]

Background: It is estimated that 78% of children experience the death of a close friend or family member by 16 years of age, yet longitudinal research examining the mental health outcomes of wider experiences of bereavement is scarce. We conducted a longitudinal investigation of the association between maternal experienced bereavement before the age of 11 years and offspring depressive and anxiety disorders at age 18 and examined moderation of this association by modifiable parental factors. Methods: We analysed data from the Avon Longitudinal Study of Parents and Children, a UK‐based birth cohort, including 9,088 child participants with data available on bereavement. Bereavement was measured via maternal report at eight timepoints until children were 11 years. Offspring depressive and anxiety‐related disorders were self‐reported at 18 years old using the Clinical Interview Schedule‐Revised (CIS‐R). The potential moderating roles of maternal anxiety, maternal depression, parental monitoring, positive parenting and negative parenting practices were examined. Results: Maternal experienced bereavement was not associated with depression or anxiety‐related disorders in early adulthood among offspring. In addition, no support was found for negative parenting practices, parental monitoring or maternal anxiety and depression as moderators of the relationship between maternal experienced bereavement and offspring mental health problems at 18 years old. Findings in relation to the moderating role of positive parenting practices were inconsistent. Conclusions: Findings suggest that a large number of children are exposed to maternal experienced bereavement. We found no evidence that maternal experienced bereavement during childhood increases the risk for offspring psychiatric disorders in early adulthood. Several methodological considerations prudent to bereavement research are discussed. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic neurological disease that negatively influences patients' quality of life (QoL). Reduced social interactions are a result of both PD symptoms and impairment in QoL, which is known as social withdrawal. Smartphones are suitable for monitoring social behaviour under the notion of digital phenotyping, as people spend significant time socialising on them. We implement year-long longitudinal research using smartphones to study social withdrawal in PD. In addition to an entire year of 24/7 continuous monitoring on smartphones, weekly social ratings and QoL are provided as self-report ground truth. Twenty-three features are extracted from more than 10 million raw data entries collected from eight participants. These features are then used to build models to reflect participants' self-report ratings. We consider the interactions that happen on smartphones, such as calls, messages and social media, and use smartphone sensors to infer face-to-face interactions. By applying multiple linear regression and Naive Bayes, our model is significantly better than just assigning mean and random guesses. The results suggest that our approach provides a more granular method for tracking social behaviour in people with PD via smartphones, and it could benefit wider communities where the social impact on patients needs attention. [ABSTRACT FROM AUTHOR]

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. This was a population-based prospective cohort study. 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. 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. Life's Simple 7 significantly mediated the associations between SES and comorbid CVD and cancer, while almost half of the associations remained unclear. [ABSTRACT FROM AUTHOR]

To examine the associations of Life's Essential 8 (LE8) and its predictive performance with mild cognitive impairment (MCI), dementia and brain MRI indices. We used cohort data from UK Biobank. LE8 was categorized into low (<50 score), moderate (50–79 score), and high (≥80 score) levels. Cox regression models considering death as a competing risk were used to estimate the hazard ratios (HRs) and 95%CI on the association between LE8 and MCI and dementia. Multivariable linear regression models were used to analyze LE8 every 10-score increase and brain MRI indices. Area under the curve (AUC) was used to measure the predictive performances of LE8. We included 126,785 participants with a mean (SD) age of 56.0 (8.0) years and 53.5 % were female. The median follow-up was 13.0 years. Compared to individuals with a low LE8 score, those with a high LE8 score were associated with decreased risk of MCI (0.49, 95%CI: 0.40–0.62), all-cause dementia (0.60, 0.44–0.80), vascular dementia (VD, 0.44, 0.21–0.94), and non-Alzheimer non-vascular dementia (NAVD, 0.55, 0.35–0.84). High LE8 score was associated with increased total brain volume, hippocampus volume, grey matter volume, and grey matter in hippocampus volume (p all ≤0.001). LE8 combined age and sex had good performance for predicting all-cause dementia (AUC: 84.1 %), AD (85.4 %), VD (87.6 %), NAVD (81.4 %), and MCI (75.3 %). Our findings only reflect the characteristics of UKB participants. High LE8 score was associated with reduced risk of MCI and dementia. It was also linked to brain MRI indices. LE8 score had good predicting performance for future risk of MCI and dementia. • High Life's Essential 8 score was associated with reduced risk of MCI and dementia. • There were joint effects between Life's Essential 8 and APOE on MCI and dementia. • Life's Essential 8 was linked to brain MRI indices. • LE8 score had good predicting performance for risk of MCI and dementia. [ABSTRACT FROM AUTHOR]

Worry and rumination (Perseverative Cognition, PC) have been associated with health behaviours, but the underlying mechanisms are unknown. Given the role of physiological experiences on perceived behavioural control (PBC) and emotion regulation on intention-health behaviour relationships, we tested whether: PC prospectively predicts poorer health behaviours; PC moderates the relationship(s) between intentions/PBC and health behaviour, as well as whether the relationship between PC and health behaviour is mediated by intentions and PBC. In a prospective design, 650 participants (mean age = 38.21 years; 49% female) completed baseline measures of intentions, PBC and PC (worry and rumination) and 590 (mean age = 38.68 years; 50% female) completed follow-up (Time 2) measures of health behaviours (physical activity, sleep, sedentary activity, unhealthy snacking) 1-week later. Worry and rumination (at T1) predicted poorer sleep quality. Worry, but not rumination, moderated PBC-physical activity frequency relations. Consistent with mediation, the indirect paths from both worry and rumination, through PBC, to sleep quality and total sleep time were significant. PC is associated with poorer sleep quality and PBC can play a mediating role in such relationships. Future research should further consider the role that PBC plays in PC-health behaviour relations. [ABSTRACT FROM AUTHOR]

Mode of birth has been linked to offspring health. Changes in DNA methylation (DNAm) may represent a potential mechanism; however, findings are heterogeneous and limited to early infancy. This preregistered study examined whether mode of birth (vaginal birth compared with elective or emergency cesarean section) affects DNAm at birth, in childhood, and adolescence and whether these effects are modified by the postnatal care environment, specifically by breastfeeding and mother–infant bonding. Using data from 876 mother–infant dyads from the U.K. Avon Longitudinal Study of Parents and Children, we examined differentially methylated cytosine-phosphate-guanine dinucleotides and regions associated with mode of birth. DNAm was quantified using Illumina Infinium Human Methylation 450 K BeadChip in cord blood (at birth) and in peripheral blood (at 7 and 15–17 years). Analyses controlled for maternal age, education, smoking during pregnancy, child sex, gestational week at birth, and batch effects. We also examined interactions of mode of birth with breastfeeding practices and mother–infant bonding. In cord blood, two cytosine-phosphate-guanine dinucleotides (cg05230316; cg13230077) were linked to mode of birth (pFDR <.050). DNAm in childhood or adolescence was not statistically associated with mode of birth (pFDR >.050), and breastfeeding and mother–infant bonding were not moderators (p >.050). Overall, findings suggest mode of birth may have a small effect on cord blood DNAm, but these effects may not persist into later developmental stages. Other postnatal influences should be considered, and further investigation is needed to address study limitations. Public Significance Statement: This study suggests that the mode of birth, whether a child is born vaginally or by emergency or elective cesarean section, has a small effect on how the child's genes are methylated in cord blood cells at birth. DNA methylation in peripheral blood cells during childhood and adolescence was not predicted by mode of birth. Breastfeeding and mother–infant bonding did not buffer the effects of mode of birth, highlighting the necessity to further investigate other postnatal factors as potential determinants of the offspring methylome across development. [ABSTRACT FROM AUTHOR]

Aims: To examine the impact of current age, age at diagnosis, and duration of diabetes on the incidence rate of complications among people with type 2 diabetes. Methods: Baseline data from 19,327 individuals with type 2 diabetes in the UK Biobank were analysed. Poisson regression was used to model incidence rates by current age, age at diagnosis, and duration of diabetes for the following outcomes: myocardial infarction (MI), heart failure (HF), stroke, end‐stage kidney diseases (ESKD), chronic kidney diseases (CKD), liver diseases, depression, and anxiety. Results: The mean age at baseline was 60.2 years, and median follow‐up was 13.9 years. Diabetes duration was significantly longer among those with younger‐onset type 2 diabetes (diagnosed at <40 years) compared to later‐onset type 2 diabetes (diagnosed at ≥40 years), 16.2 and 5.3 years, respectively. Incidence rates of MI, HF, stroke, and CKD had strong positive associations with age and duration of diabetes, whereas incidence rates of ESKD liver diseases, and anxiety mainly depended on duration of diabetes. The incidence rates of depression showed minor variation by age and duration of diabetes and were highest among those diagnosed at earlier ages. No clear evidence of an effect of age of onset of diabetes on risk of complications was apparent after accounting for current age and duration of diabetes. Conclusions: Our study indicates age at diagnosis of diabetes does not significantly impact the incidence of complications, independently of the duration of diabetes. Instead, complications are primarily influenced by current age and diabetes duration. [ABSTRACT FROM AUTHOR]

The Perfectionism Social Disconnection Model (PSDM) and the Existential Model of Perfectionism and Depressive Symptoms (EMPDS) are promising models of perfectionism and psychopathology. However, research examining suicide ideation within the PSDM is scarce, and no research has examined suicide ideation as an outcome in the EMPDS. Moreover, tests of the PSDM and EMPDS have been conducted separately and most research has examined the PSDM and EMPDS using cross-sectional or two-wave longitudinal designs, which do not provide a satisfactory test of mediation. In the current study, we addressed these limitations by testing whether perfectionism confers vulnerability to suicide ideation via feelings of mattering and anti-mattering (from the PSDM) and via difficulty accepting the past (from the EMPDS) in a three-wave longitudinal design in two independent samples of undergraduate students and community adults. Participants completed measures on three occasions over 6 weeks. Findings revealed that socially prescribed perfectionism indirectly predicted suicide ideation via difficulty accepting the past in both samples. In addition, in the undergraduate sample only, socially prescribed perfectionism indirectly predicted higher suicide ideation via anti-mattering, and self-oriented perfectionism indirectly predicted higher suicide ideation via mattering. Based on our findings, we advocate for future research to include suicide ideation in the PSDM and EMPDS, to integrate explanatory models, and to examine a mattering-specific EMPDS. [ABSTRACT FROM AUTHOR]

Background Police work can be sedentary and stressful, negatively impacting health and wellbeing. In a novel co-creation approach, we used the Behavior Change Wheel (BCW) and Double Diamond (DD) design framework to guide the collaborative design and development of a sedentary behavior intervention in the control rooms of two British police forces. Methods Multiple stakeholders participated in four phases of research. In Phase 1, a literature review, focus groups (n  = 20) and interviews (n  = 10) were conducted to 'discover' the relationship between physical activity and wellbeing in the police. In Phase 2, a steering group consolidated Phase 1 findings to 'define' a specific behavior for intervention. Phases 3 and 4 'developed' the intervention across six workshops with control room workers and six steering group workshops. Results The co-creation process identified contextual sedentary behavior as the target behavior, driven by behavioral regulation, social influence and social norms. The sedentary behavior intervention targeted these drivers and aimed to engage control room workers in short bursts of physical activity throughout their shifts. Key intervention features targeted involvement of staff in decision-making and embedding physical activity into work practices. Conclusions The BCW and DD can be combined to co-create evidence-based and participant-informed interventions and translate science into action. [ABSTRACT FROM AUTHOR]

Aims Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. Methods and results Utilizing the UK Biobank cohort, we assessed biological age using the Klemera–Doubal and PhenoAge methods. BAA was quantified by residual analysis compared with chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analysis was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF [26% per standard deviation (SD) increase in KDM-BA acceleration, 95% confidence intervals (CI): 23–28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32–35%]. Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. Conclusion In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Self‐management is a key component of successful chronic kidney disease (CKD) management. Here, we present the findings from the internal pilot of a multicentre randomised controlled trial (RCT) aimed to test the effect of a digital self‐management programme ('My Kidneys & Me' (MK&M)). Methods: Participants (aged ≥18 years and CKD stages 3‐4) were recruited from hospital kidney services across England. Study processes were completed virtually. Participants were randomised 2:1 to either intervention (MK&M) or control group. The first 60 participants recruited were included in a 10‐week internal pilot which assessed study feasibility and acceptability against pre‐specified progression criteria: 1) eligibility and recruitment, acceptability of 2) randomisation and 3) outcomes, 4) MK&M activation, and 5) retention and attrition rates. Semi‐structured interviews further explored views on trial participation. Results: Of the 60 participants recruited, 41 were randomised to MK&M and 19 to control. All participants completed baseline measures and 62% (n=37) completed post‐intervention outcome measures. All progression criteria met the minimum thresholds to proceed. Nine participants were interviewed. The themes identified were satisfaction with study recruitment processes (openness to participate, reading and agreeing to "terms and conditions"), acceptability of study design (remote study participation, acceptability of randomisation, completion of online assessment(s)), and methods to improve recruitment and retention (personalised approach, follow‐up communication). Conclusion: This internal pilot demonstrated the feasibility and acceptability of a virtually run RCT. Progression criteria thresholds to proceed to the definitive RCT were met. Areas for improvement were identified and protocol amendments were made to improve trial delivery. [ABSTRACT FROM AUTHOR]

Objective The aims of the study were to identify prognostic factors associated with health care outcomes in patients with musculoskeletal (MSK) conditions in primary care and to determine whether characteristics associated with choice of care modify treatment effects of a direct-access physical therapist–led pathway in addition to general practitioner (GP)–led care compared to GP-led care alone. Methods A secondary analysis of a 2-parallel-arm, cluster randomized controlled trial involving general practices in the United Kingdom was conducted. Practices were randomized to continue offering GP-led care or to also offer a direct-access physical therapist–led pathway. Data from adults with MSK conditions who completed the 6-month follow-up questionnaire were analyzed. Outcomes included physical health, opioid prescription, and self-reported health care utilization over 6 months. Treatment effect modifiers were selected a priori from associations in observational studies. Multivariable regression models identified potential prognostic factors, and interaction analysis tested for potential treatment effect modifiers. Results Analysis of 767 participants indicated that baseline pain self-efficacy, pain severity, and having low back pain statistically predicted outcomes at 6 months. Higher pain self-efficacy scores at baseline were associated with improved physical health scores, reduced opioid prescription, and less health care utilization. Higher bodily pain at baseline and having low back pain were associated with worse physical health scores and increased opioid prescription. Main interaction analyses did not reveal that patients' age, level of education, duration of symptoms, or MSK presentation influenced response to treatment, but visual trends suggested those in the older age group proceeded to fewer opioid prescriptions and utilized less health care when offered direct access to physical therapy. Conclusions Patients with MSK conditions with lower levels of pain self-efficacy, higher pain severity, and presenting with low back pain have less favorable clinical and health care outcomes in primary care. Prespecified characteristics did not modify the treatment effect of the offer of a direct-access physical therapist–led pathway compared to GP-led care. Impact Patients with MSK conditions receiving primary care in the form of direct-access physical therapist–led or GP-led care who have lower levels of self-efficacy, higher pain severity, and low back pain are likely to have a less favorable prognosis. Age and duration of symptoms should be explored as potential patient characteristics that modify the treatment response to a direct-access physical therapist–led model of care. [ABSTRACT FROM AUTHOR]

Background and aims: The relationship between alcohol consumption and age‐related diseases is inconsistent. Biological age (BA) serves as both a precursor and a predictor of age‐related diseases; however, longitudinal associations between alcohol consumption and BA in middle‐aged and older people remain unclear. We measured whether there was a longitudinal association between drinking frequency and pure alcohol intake with BA among middle‐aged and older people. Design and setting and participants: This study involved two prospective cohort studies, set in Southwestern China and the United Kingdom. A total of 8046 participants from the China Multi‐Ethnic Cohort study (CMEC) and 5412 participants from the UK Biobank (UKB), aged 30–79 years, took part, with complete data from two waves of clinical biomarkers. Measurements: BA was calculated by the Klemera Doubal's method. Accelerated BA equalled BA minus chronological age. Drinking frequency and pure alcohol intake were obtained through self‐reported questionnaires. Drinking frequency in the past year was classified as current non‐drinking, occasional (monthly drinking) and regular (weekly drinking). Findings: Compared with consistent current non‐drinkers, more frequent drinkers [CMEC: β = 0.46, 95% confidence interval (CI) = 0.13–0.80; UKB: β = 0.65, 95% CI = 0.01–1.29)], less frequent drinkers (CMEC: β = 0.62, 95% CI = 0.37–0.87; UKB: β = 0.54, 95% CI = −0.01–1.09), consistent occasional drinkers (CMEC: β = 0.51, 95% CI = 0.23–0.79; UKB: β = 0.63, 95% CI = 0.13–1.13) and consistent regular drinkers (CMEC: β = 0.56, 95% CI = 0.17–0.95; UKB: β = 0.46, 95% CI = 0.00–0.91) exhibited increased accelerated BA. A non‐linear relationship between pure alcohol intake and accelerated BA was observed among consistent regular drinkers. Conclusions: In middle‐aged and older people, any change in drinking frequency and any amount of pure alcohol intake seem to be positively associated with acceleration of biological ageing, compared with maintaining abstinence. [ABSTRACT FROM AUTHOR]

Background and aims: The relationship between alcohol consumption and age-related diseases is inconsistent. Biological age (BA) serves as both a precursor and a predictor of age-related diseases; however, longitudinal associations between alcohol consumption and BA in middle-aged and older people remain unclear. We measured whether there was a longitudinal association between drinking frequency and pure alcohol intake with BA among middle-aged and older people. Design and setting and participants: This study involved two prospective cohort studies, set in Southwestern China and the United Kingdom. A total of 8046 participants from the China Multi-Ethnic Cohort study (CMEC) and 5412 participants from the UK Biobank (UKB), aged 30-79 years, took part, with complete data from two waves of clinical biomarkers. Measurements: BA was calculated by the Klemera Doubal's method. Accelerated BA equalled BA minus chronological age. Drinking frequency and pure alcohol intake were obtained through self-reported questionnaires. Drinking frequency in the past year was classified as current non-drinking, occasional (monthly drinking) and regular (weekly drinking). Findings: Compared with consistent current non-drinkers, more frequent drinkers [CMEC: β = 0.46, 95% confidence interval (CI) = 0.13-0.80; UKB: β = 0.65, 95% CI = 0.01-1.29)], less frequent drinkers (CMEC: β = 0.62, 95% CI = 0.37-0.87; UKB: β = 0.54, 95% CI = -0.01-1.09), consistent occasional drinkers (CMEC: β = 0.51, 95% CI = 0.23-0.79; UKB: β = 0.63, 95% CI = 0.13-1.13) and consistent regular drinkers (CMEC: β = 0.56, 95% CI = 0.17-0.95; UKB: β = 0.46, 95% CI = 0.00-0.91) exhibited increased accelerated BA. A non-linear relationship between pure alcohol intake and accelerated BA was observed among consistent regular drinkers. Conclusions: In middle-aged and older people, any change in drinking frequency and any amount of pure alcohol intake seem to be positively associated with acceleration of biological ageing, compared with maintaining abstinence. [ABSTRACT FROM AUTHOR]

Background: Recognition of atypical anorexia nervosa (AAN) has challenged underweight as a defining factor of illness severity in anorexia nervosa (AN). The present study aimed to compare rates of medical instability in adolescents with underweight (AN) and non‐underweight (AAN) anorexia nervosa. Methods: The study examined assessment data from specialist eating disorder services in the UK between January and December 2022. Participants (n = 205) aged 11–18 years were recruited across eight eating disorder clinics and diagnosed with AN (n = 113) or AAN (n = 92) after clinical assessment. Parameters associated with risk of medical instability were compared between AN and AAN groups, using t tests and regression analysis. Results: Rates of bradycardia and hypotension did not differ significantly between AN and AAN groups (p = 0.239 and p = 0.289). Although white blood cell counts were lower in the AN group, rates of leukopaenia could not be statistically compared as a result of there being too few counts in at least one group. No incidences of hypophosphataemia were found in the sample. A significant regression equation was found for percentage median body mass index, but not rate of weight loss, as a predictor of blood pressure, serum phosphorous and magnesium. Conclusions: Our findings indicate that medical instability occurs across a range of body weights in young people with AN and AAN. Although certain parameters of risk such as blood pressure, serum phosphorous and magnesium may be worsened at lower weight, both AN and AAN are serious mental health conditions that can lead to medical instability. Highlights: The study compared rates of medical instability in adolescents with underweight (AN) and non‐underweight (AAN) anorexia nervosa.The findings support the conclusion that, although certain parameters of risk (e.g., blood pressure) may be worsened by lower weight, both AN and AAN are serious illnesses that can lead to medical compromise. [ABSTRACT FROM AUTHOR]

Aims: To estimate the association between long‐term changes in frailty and the risk of incident type 2 diabetes (T2DM) and to evaluate the effect of preventing the worsening of frailty on the risk of T2DM. Methods: We included 348 205 participants free of baseline T2DM and with frailty phenotype (FP) data from the UK Biobank; among them, 36 175 had at least one follow‐up assessment. According to their FP score, participants were grouped into nonfrailty, prefrailty and frailty groups. Frailty assessed at baseline and at follow‐up was used to derive the trajectory of frailty (ΔFP). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Compared with those in the nonfrailty group at baseline, the HRs of T2DM for the prefrailty and frailty groups were 1.38 (95% CI 1.33–1.43) and 1.69 (95% CI 1.59–1.79), respectively (both p < 0.001), in the multivariable‐adjusted model. During a median follow‐up of 5.4 years after the final assessment, data for 472 T2DM patients were recorded. A 1‐point increase in the final FP was associated with a 25% (95% CI 1.14–1.38; p < 0.001) increased risk of T2DM. For the trajectory of frailty, each 0.5‐point/year increase in ΔFP was associated with a 52% (95% CI 1.18–1.97; p < 0.001) greater risk of T2DM, independent of the FP score at baseline. Compared with those that remained in the nonfrailty group, the greatest risk of T2DM over time was prefrailty aggravation (HR 3.03, 95% CI 2.00–4.58; p < 0.001). Using the frailty index did not materially change the results. Conclusions: Long‐term changes in frailty were associated with the risk of incident T2DM, irrespective of baseline frailty status. Preventing the worsening of frailty may reduce T2DM risk. [ABSTRACT FROM AUTHOR]

Childhood conduct problems and head injuries share a bidirectional association, but how this affects the risk of adolescent delinquency is unknown. Due to their similar underlying mechanisms (i.e. increased impulsivity), this study aims to identify whether their co-occurrence increases the risk of adolescent delinquency. Data was obtained from 11,272 children at age 14 and 10,244 at age 17 years enrolled in the UK Millennium Cohort Study. Conduct problem symptoms (via the Strengths and Difficulties Questionnaire) and head injuries were parent reported from ages 3 to 14 years. Delinquency was self-reported at ages 14 and 17 including substance use, criminality, and antisocial behaviour. Incident rate ratios (IRR) were estimated for delinquency at ages 14 and 17 by childhood conduct problem and head injury status. Co-occurring head injuries and high conduct problem symptoms presented the greatest risk for overall delinquency and substance use at age 14 compared to those with the presence of one or neither (IRRs from 1.20 to 1.60). At age 17, conduct problems (with or without co-occurring head injuries) presented the greatest risk for overall delinquency, substance use, and antisocial behaviour. There was no evidence for an increased risk of delinquency at ages 14 or 17 following a head injury only. Whilst these findings suggest childhood head injuries alone do not increase the risk of adolescent delinquency, when co-occurring alongside high conduct problem symptoms there is a heightened earlier risk. These results provide further insight into adolescent delinquency and the outcomes of co-occurring childhood head injury and conduct problem symptoms. [ABSTRACT FROM AUTHOR]

Objectives To evaluate a strategy designed to optimize care and increase uptake of urate-lowering therapy (ULT) during hospitalizations for gout flares. Methods We conducted a prospective cohort study to evaluate a strategy that combined optimal in-hospital gout management with a nurse-led, follow-up appointment, followed by handover to primary care. Outcomes, including ULT initiation, urate target attainment and re-hospitalization rates, were compared between patients hospitalized for flares in the 12 months post-implementation and a retrospective cohort of hospitalized patients from 12 months pre-implementation. Results One hundred and nineteen and 108 patients, respectively, were hospitalized for gout flares in the 12 months pre- and post-implementation. For patients with 6-month follow-up data available (n  = 94 and n  = 97, respectively), the proportion newly initiated on ULT increased from 49.2% pre-implementation to 92.3% post-implementation (age/sex-adjusted odds ratio [aOR] 11.5; 95% CI 4.36, 30.5; P  < 0.001). After implementation, more patients achieved a serum urate ≤360 μmol/l within 6 months of discharge (10.6% pre-implementation vs 26.8% post-implementation; aOR 3.04; 95% CI 1.36, 6.78; P  = 0.007). The proportion of patients re-hospitalized for flares was 14.9% pre-implementation vs 9.3% post-implementation (aOR 0.53; 95% CI 0.22, 1.32; P  = 0.18). Conclusion Over 90% of patients were initiated on ULT after implementing a strategy to optimize hospital gout care. Despite increased initiation of ULT during flares, recurrent hospitalizations were not more frequent following implementation. Significant relative improvements in urate target attainment were observed post-implementation; however, for the majority of hospitalized gout patients to achieve urate targets, closer primary–secondary care integration is still needed. [ABSTRACT FROM AUTHOR]

Objectives Adults with RA are being switched from etanercept originator to biosimilar in non-medical/cost-saving switching. This analysis aims to investigate outcomes in these patients, including (i) drug survival and (ii) disease activity at 6 months and 12 months, compared with those who remain on the originator. Methods Using BSRBR-RA, those who switched directly from etanercept originator to biosimilar were identified and matched to patients receiving the originator, based on gender, age, disease duration and originator start year. Drug survival was calculated; Cox-proportional hazard models assessed differences in drug persistence between those who switched vs remaining on originator. Change in DAS28 after 6 months and 12 months was compared between cohorts. Multiple imputation was used. Results A total of 1024 adults with RA switching from etanercept originator to biosimilar were included, with a matched cohort of patients remaining on the originator. Patients who switched onto a biosimilar product were no more likely to discontinue etanercept treatment vs those who remained on the originator; hazard ratio 1.06 (95%CI 0.89–1.26), with 65% of patients remaining on treatment at three years. Ninety-five (9%) patients switched back to the originator within the first year. After 6 months and 12 months, biosimilar patients were no more likely to have a worsening of DAS28 (>0.6 units) compared with those who remained on the originator. Conclusions This is the largest matched comparative effectiveness analysis showing patients switching from etanercept originator to biosimilar appearing to do just as well with regard to disease activity and drug persistence compared with those who remained on the originator. These data will be reassuring to clinicians and patients regarding non-medical switching. [ABSTRACT FROM AUTHOR]

Purpose: The association between type 2 diabetes mellitus (T2DM), lifestyle factors, and the risk of osteoporosis (OP) is well-established. However, the impact of a healthy lifestyle on diabetes-related osteoporosis needs further investigation. Our objective was to explore if a combination of healthy lifestyle factors could mitigate the risk of OP in individuals with type 2 diabetes. Methods: This longitudinal analysis included 237,725 middle-aged and older participants. An overall lifestyle score, ranging from 0 to 7, was calculated by assigning a point for each of the seven healthy lifestyle factors, including no current smoking, non-excessive alcohol consumption, regular physical activity, healthy diet, adequate sleep duration, less sedentary behavior, and adequate sunshine exposure. Results: During a median follow-up 12.21 years, 5760 OP cases were documented. Participants with T2DM showed a higher risk of OP than those without diabetes. Compared with participants without diabetes who had a lifestyle score of 6–7, the hazard ratios (HRs) for OP were 1.58 (95% CI 1.23–2.03), 1.62 (95% CI 1.16–2.25), and 2.58 (95% CI 1.64–4.05) for participants with T2DM who had a lifestyle score of 4, 3, and 0–2, respectively. There was a graded association between higher lifestyle scores and lower risks of incident OP among participants without diabetes as well as among those with T2DM. We estimated that the population attributable fraction for not adhering to 6–7 lifestyle behaviors was 15.7%. Conclusions: Participants with T2DM who adhered to a variety of healthy lifestyle factors demonstrated a substantially reduced risk of developing OP. [ABSTRACT FROM AUTHOR]

Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2–4 years and 4–6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. The generalizability to other ethnic groups is limited. This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows. • Evidence is scarce on association between a holistic healthy lifestyle and depression and anxiety comorbidity. • Trajectory and time courses of mental disorders need consideration. • Healthy lifestyle adherence inversely linked to mental disorder progression and prognosis. • Each lifestyle score increase reduces depression to comorbid anxiety by 6% and anxiety to comorbid depression by 5%. • Important progression windows were detected in the protective role of a holistic healthy lifestyle. [ABSTRACT FROM AUTHOR]

Child safeguarding services intervene when a child is at risk of serious emotional or physical harm. Oxfordshire County Council is implementing a new approach to child safeguarding (Family Solutions Plus [FSP]) with a greater focus on whole family support and reducing the need for foster care. We sampled two cohorts of children closed within 1 year and examined the time spent in services. The sample included 474 children entering services before the new model's implementation and 561 children after. A greater proportion of children receiving FSP required a single care plan before their case was closed (85.9%; 69.4%, p < 0.001) and only experienced the lowest level plan (74.5%; 61.8%, p < 0.001). On average, this group spent less time in services for the period being observed (MD = 17.58, 95% confidence interval = 6.19, 28.96). At this early stage, no significant reduction in the number of children requiring foster care was seen (5.5%; 3.9%, p = 0.23). These initial findings suggest a potential association of FSP with a reduced number and level of care plans as well as length of time. Local authorities in England may investigate further whether FSP is a potentially useful model in improving safeguarding services. [ABSTRACT FROM AUTHOR]

Cognitive control is a predictor of later‐life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24‐month. We evaluated a tablet‐based assessment of cognitive control among infants aged 18‐ and 24‐month. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N = 60, 30 female) completed the tablet‐task at 18‐ and 24‐month of age. Attentional disengagement and general cognitive development were assessed at 5‐, 8‐, 12‐, 18‐ and 24‐month using an eye‐tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age‐related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye‐tracking task revealed that slower attentional disengagement at 8‐month, but faster disengagement at 18‐month, predicted higher cognitive control scores at 24‐month. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development. [ABSTRACT FROM AUTHOR]

Background UK studies examining vitiligo burden and vitiligo-related healthcare resource utilization (HCRU) are lacking. Objective To describe the incidence and prevalence of vitiligo, the demographic and clinical characteristics of patients with vitiligo, vitiligo burden, HCRU, incidence of mental health comorbidities and management strategies, including treatment patterns. Methods This retrospective study used UK Clinical Practice Research Datalink and Hospital Episode Statistics databases to analyse patients with vitiligo from 1 January 2010 to 31 December 2021. Results Among 17 239 incident patients, mean incidence of vitiligo was 0.16 (2010–2021) per 1000 person-years [PY; range 0.10 (2020–COVID-19) to 0.19 (2010/2013/2018)]; among 66 217 prevalent patients, prevalence increased from 0.21% (2010) to 0.38% (2021). The most common comorbidities recorded after vitiligo diagnosis were diabetes (19.4%), eczema (8.9%), thyroid disease (7.5%) and rheumatoid arthritis (6.9%). Mental health diagnoses recorded at any time included depression and/or anxiety (24.6%), depression (18.5%), anxiety (16.0%) and sleep disturbance (12.7%), and recorded after vitiligo diagnosis in 6.4%, 4.4%, 5.5% and 3.9%, respectively. Mental health comorbidities were more common in White (e.g. depression and/or anxiety 29.0%) than in Black (18.8%) and Asian (16.1%) patients. In adolescents, depression and/or anxiety was most commonly diagnosed after a vitiligo diagnosis than before (7.4% vs. 1.8%). Healthcare resources were used most frequently in the first year after vitiligo diagnosis (incident cohort), typically dermatology-related outpatient appointments (101.9/100 PY) and general practitioner consultations (97.9/100 PY). In the year after diagnosis, 60.8% of incident patients did not receive vitiligo-related treatment (i.e. topical corticosteroids, topical calcineurin inhibitors, oral corticosteroids or phototherapy), increasing to 82.0% the next year; median time from diagnosis to first treatment was 34.0 months (95% confidence interval 31.6–36.4). Antidepressants and/or anxiolytics were recorded for 16.7% of incident patients in the year after diagnosis. In 2019, 85.0% of prevalent patients did not receive vitiligo-related treatments. Conclusion Most patients were not on vitiligo-related treatments within a year of diagnosis, with the time to first treatment exceeding 2 years, suggesting that vitiligo may be dismissed as unimportant. New effective treatments, early initiation and psychological intervention and support are needed to reduce the vitiligo burden on patients. [ABSTRACT FROM AUTHOR]

Purpose: Incomplete partition type II (IP-II) is characterized by specific histological features and radiological appearance. It may occur in isolation or in association with an enlarged vestibular aqueduct (EVA). Among those with IP-II and EVA, a subset has a diagnosis of Pendred syndrome. This study aimed to explore the prevalence of isolated IP-II, IP-II with EVA, and cases with a genetic or syndromic basis in our cohort. Methods: From a large, multicentre database of dysplastic cochleae (446 patients, 892 temporal bones), those with imaging features of IP-II were examined in detail, including whether there was a genetic or syndromic association. Results: A total of 78 patients with IP-II were identified. Among these, 55 patients had bilateral IP-II and EVA (only 12 with typical Mondini triad), 8 with bilateral IP-II and normal VA, 2 with bilateral IP-II and unilateral EVA, and 13 with unilateral IP-II (9 with unilateral EVA). Among the group with bilateral IP-II and bilateral EVA in whom genetic analysis was available, 14 out of 29 (48%) had SLC26A4 mutations and a diagnosis of Pendred syndrome, 1 had a FOXI1 mutation, and a few other genetic abnormalities; none had KCNJ10 pathogenic variants. Conclusion: Bilateral IP-II-bilateral EVA may be seen in the context of Pendred syndrome (SLC26A4 or FOXI1 mutations) but, in the majority of our cohort, no genetic abnormalities were found, suggesting the possibility of unknown genetic associations. IP-II in isolation (without EVA) is favored to be genetic when bilateral, although the cause is often unknown. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate the association between OA and treatment with dementia risk and structural brain abnormalities. Methods We recruited a total of 466,460 individuals from the UK Biobank to investigate the impact of OA on the incidence of dementia. Among the total population, there were 63,081 participants diagnosed with OA. We subsequently categorised the OA patients into medication and surgery groups based on treatment routes. Cox regression models explored the associations between OA/OA treatment and dementia risk, with the results represented as hazard ratios (HRs) and 95% confidence intervals (95% CI). Linear regression models assessed the associations of OA/OA therapy with alterations in cortical structure. Results During an average of 11.90 (± 1.01) years of follow-up, 5,627 individuals were diagnosed with all-cause dementia (ACD), including 2,438 AD (Alzheimer's disease), and 1,312 VaD (vascular dementia) cases. Results revealed that OA was associated with the elevated risk of ACD (HR: 1.116; 95% CI: 1.039–1.199) and AD (HR: 1.127; 95% CI: 1.013–1.254). OA therapy lowered the risk of dementia in both medication group (HR: 0.746; 95% CI: 0.652–0.854) and surgery group (HR: 0.841; 95% CI: 0.736–0.960). OA was negatively associated with cortical area, especially precentral, postcentral and temporal regions. Conclusions Osteoarthritis increased the likelihood of developing dementia, and had an association with regional brain atrophy. OA treatment lowered the dementia risk. OA is a promising modifiable risk factor for dementia. [ABSTRACT FROM AUTHOR]

Objectives: The addition of fluoride to community drinking water supplies has been a long‐standing public health intervention to improve dental health. However, the evidence of cost‐effectiveness in the UK currently lacks a contemporary focus, being limited to a period with higher incidence of caries. A water fluoridation scheme in West Cumbria, United Kingdom, provided a unique opportunity to study the contemporary impact of water fluoridation. This study evaluates the cost‐effectiveness of water fluoridation over a 5–6 years follow‐up period in two distinct cohorts: children exposed to water fluoridation in utero and those exposed from the age of 5. Methods: Cost‐effectiveness was summarized employing incremental cost‐effectiveness ratios (ICER, cost per quality adjusted life year (QALY) gained). Costs included those from the National Health Service (NHS) and local authority perspective, encompassing capital and running costs of water fluoridation, as well as NHS dental activity. The measure of health benefit was the QALY, with utility determined using the Child Health Utility 9‐Dimension questionnaire. To account for uncertainty, estimates of net cost and outcomes were bootstrapped (10 000 bootstraps) to generate cost‐effectiveness acceptability curves and sensitivity analysis performed with alternative specifications. Results: There were 306 participants in the birth cohort (189 and 117 in the non‐fluoridated and fluoridated groups, respectively) and 271 in the older school cohort (159 and 112, respectively). In both cohorts, there was evidence of small gains in QALYs for the fluoridated group compared to the non‐fluoridated group and reductions in NHS dental service cost that exceeded the cost of fluoridation. For both cohorts and across all sensitivity analyses, there were high probabilities (>62%) of water fluoridation being cost‐effective with a willingness to pay threshold of £20 000 per QALY. Conclusions: This analysis provides current economic evidence that water fluoridation is likely to be cost‐effective. The findings contribute valuable contemporary evidence in support of the economic viability of water fluoridation scheme. [ABSTRACT FROM AUTHOR]

Academics and policymakers have suggested making flexible work arrangements (FWAs) the default in workplaces to promote a family-friendly workplace culture conducive to having and raising children. However, systematic research investigating how FWAs, as a long-term approach to negotiating work–family spheres, are related to fertility among dual-earner heterosexual couples is limited. Drawing on the linked-lives perspective, we theorize the relationship between FWAs and fertility among couples and potential variation depending on the interplay of both spouses' work and family characteristics. We test our hypotheses using longitudinal couple-level dyadic data in the United Kingdom (2010–2022). We find that although FWA availability alone is unrelated to fertility, wives' (not husbands') FWA use is significantly associated with a higher probability of experiencing a first birth. Moreover, the effect of wives' FWA use is particularly pronounced when both spouses work in professional and managerial occupations and when husbands contribute a larger proportion of income and at least equal housework. This study reveals a gendered effect of FWAs on fertility across work–family arrangements, deepening our understanding of couple-level dynamics in the fertility process. [ABSTRACT FROM AUTHOR]

Purpose: It is unclear whether common maternal infections during pregnancy are risk factors for adverse birth outcomes. We assessed the association between self-reported infections during pregnancy with preterm birth and small-for-gestational-age (SGA) in an international cohort consortium. Methods: Data on 120,507 pregnant women were obtained from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA. Self-reported common infections during pregnancy included influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections, cystitis, urinary tract infection, and the symptoms fever and diarrhoea. Birth outcomes included preterm birth, low birth weight and SGA. Associations between maternal infections and birth outcomes were first assessed using Poisson regression in each cohort and then pooled using random-effect meta-analysis. Risk ratios (RR) and 95% confidence intervals (CI) were calculated, adjusted for potential confounders. Results: Vaginal infections (pooled RR, 1.10; 95% CI, 1.02–1.20) and urinary tract infections (pooled RR, 1.17; 95% CI, 1.09–1.26) during pregnancy were associated with higher risk of preterm birth. Similar associations with low birth weight were also observed for these two infections. Fever during pregnancy was associated with higher risk of SGA (pooled RR, 1.07; 95% CI, 1.02–1.12). No other significant associations were observed between maternal infections/symptoms and birth outcomes. Conclusion: Vaginal infections and urinary infections during pregnancy were associated with a small increased risk of preterm birth and low birth weight, whereas fever was associated with SGA. These findings require confirmation in future studies with laboratory-confirmed infection diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Surgical voice restoration (SVR) is associated with improved patient quality of life following laryngectomy. This study aims to determine the impact of the COVID-19 pandemic on patients with SVR and analyse the complications in this cohort of patients. Method: A retrospective review of all patients with SVR at a single tertiary ear, nose, and throat (ENT) unit in the UK for 12 months during the COVID-19 pandemic, with comparison to the preceding 12 months. A survey was also administered to assess patients' experiences during the pandemic. Result: Thirty-six patients were included in this study. During the pandemic period, 19.5% (n = 7) patients had significant complications, with five patients needing surgery to restore speech. In the 12 months pre-pandemic, 13.5% (n = 5) had significant complications, although none required surgery to restore speech. Six patients (19.4%) felt these complications were avoidable in normal circumstances. Further, 30.5% (n = 11) of patients reported a delay in seeking medical attention due to concerns about their vulnerability to COVID-19. Conclusion: The COVID-19 pandemic has had an impact on many patients with SVR. This has resulted in a large proportion of patients experiencing delayed care, a loss of voice, a need for further surgical intervention, and negative impacts on their quality of life. [ABSTRACT FROM AUTHOR]

Aims With an ageing population, the presence of asymptomatic valvular heart disease (VHD) in the community remains unknown. The aim of this study is to determine the prevalence and associated factors of asymptomatic VHD in individuals ≥60 years old and to evaluate the feasibility of echocardiographic screening for VHD in this population. Methods and results This was a prospective cohort study conducted between 2007 and 2016 in the UK. Asymptomatic patients with no prior indication for echocardiography were invited to participate and evaluated with a health questionnaire, clinical examination, and transthoracic echocardiography. A total of 10,000 individuals were invited through their general practices. A total of 5429 volunteered to participate, of whom 4237 were eligible for inclusion. VHD was diagnosed in more than a quarter of patients (28.2%). The most common types of VHD were regurgitation of the tricuspid (13.8%), mitral (12.8%), and aortic (8.3%) valves (trivial regurgitation was not included). The rate of prevalence of clinically significant VHD was 2.4% (2.2% moderate and 0.2% severe), with mitral and aortic regurgitation being the most common. The only parameter associated with significant VHD was age (odds ratio 1.07 per 1 year increment, 95% confidence interval 1.05–1.09, P < 0.001). The number needed to scan to diagnose one clinically significant case of VHD is 42 for individuals ≥60 and 15 for those ≥75 years old. Conclusion Asymptomatic VHD is present in a significant proportion of otherwise healthy individuals without known VHD over 60 years old. Age is strongly associated with an increased incidence of significant VHD. [ABSTRACT FROM AUTHOR]

Background: Transtibial prosthetic sockets are often grouped into patella tendon bearing (PTB) or total surface bearing (TSB) designs, but many variations in rectifications are used to apply these principles to an individual’s personalised socket. Prosthetists currently have little objective evidence to assist them as they make design choices. Aims: To compare rectifications made by experienced prosthetists across a range of patient demographics and limb shapes to improve understanding of socket design strategies. Methodology: 163 residual limb surface scans and corresponding CAD/CAM sockets were analysed for 134 randomly selected individuals in a UK prosthetics service. This included 142 PTB and 21 TSB designs. The limb and socket scans were compared to determine the location and size of rectifications. Rectifications were compiled for PTB and TSB designs, and associations between different rectification sizes were assessed using a variety of methods including linear regression, kernel density estimation (KDE) and a Naïve Bayes (NB) classification. Results: Differences in design features were apparent between PTB and TSB sockets, notably for paratibial carves, gross volume reduction and distal end elongation. However, socket designs varied across a spectrum, with most showing a hybrid of the PTB and TSB principles. Pairwise correlations were observed between the size of some rectifications (e.g., paratibial carves; fibular head build and gross volume reduction). Conversely, the patellar tendon carve depth was not associated significantly with any other rectification, indicating its relative design insensitivity. The Naïve Bayes classifier produced design patterns consistent with expert clinician practice. For example, subtle local rectifications were associated with a large volume reduction (i.e., a TSB-like design), whereas more substantial local rectifications (i.e., a PTB-like design) were associated with a low volume reduction. Clinical implications: This study demonstrates how we might learn from design records to support education and enhance evidence-based socket design. The method could be used to predict design features for newly presenting patients, based on categorisations of their limb shape and other demographics, implemented alongside expert clinical judgement as smart CAD/CAM design templates. [ABSTRACT FROM AUTHOR]

In order to slow the spread of COVID-19, on March 23, 2020, a strict lockdown was implemented in the UK. This was followed by alternating periods of less restrictive lockdowns until most public health restrictions were lifted in the summer of 2021. While these measures were necessary, they significantly affected people's daily activities, lifestyles, and mental well-being. This paper presents a longitudinal research study that focused on females aged 55 + in the UK, aiming to understand how COVID-19 and the subsequent 15-month period of lockdowns affected their lifestyles and emotions. The study collected data through online surveys, where respondents reported the frequency and mode of access to activities, and their positive and negative emotional experiences during distinct study phases that encompassed both lockdown and less strict periods. In contrast to previous studies highlighting vulnerabilities for females and the elderly during lockdowns, this research found that the studied group maintained an overall positive outlook throughout the study period and successfully adapted to the lockdowns by increasing their engagement in certain activities, in particular, activities like 'getting active'. In addition, our findings indicate rapid adaptive behaviour change towards many online activities, such as cultural activities. However, the study also revealed negative emotions and a decrease in some activities during the second lockdown in 2020 and the subsequent lockdowns in 2021, underscoring the challenges inherent in prolonged periods of confinement. In addition, the study found negative affect associated with some activities, including working and studying from home. The findings provide valuable insights into how females aged over 55 coped with stressful circumstances, which can inform the development of resilient and mental health-conscious public health policies and responses in preparation for future pandemics or other hazards. [ABSTRACT FROM AUTHOR]

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD. Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association. Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2:OR 1.22, 95% CI 1.17-1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38-1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59-1.74, p < 0.001). The results of prospective analyses were similar. Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD. [ABSTRACT FROM AUTHOR]

Aims: The association of sleep traits (insomnia, sleep duration, chronotype, daytime sleepiness, and snoring) with benign prostatic hyperplasia (BPH) is unclear. This research aimed to examine the effects of sleep traits on BPH risk. Methods: A total of 170 241 men aged 38 to 73 years from UK Biobank were included. An overall healthy sleep score was created based on five sleep traits. A Cox regression model was utilized to compute adjusted hazard ratios (HRs) and population attributable fractions (PAFs) with 95% confidence intervals (CIs) for BPH risk in relation to sleep traits. Results: During a median of 12.0 years follow‐up, 13 026 incident BPH cases occurred. We observed that sleep duration (7–8 h/d; HR 0.95; 95% CI 0.92–0.99), no frequent insomnia (HR 0.71; 95% CI 0.69–0.74), and no frequent daytime sleepiness (HR 0.86; 95% CI 0.79–0.93) were significantly related to reduced BPH risk. Each one‐point increment of the healthy sleep score was related to a decreased BPH risk, with an adjusted HR of 0.90 (95% CI 0.89–0.92). The multivariable‐adjusted HR in men adopting five versus zero to one low‐risk sleep traits was 0.68 (95% CI 0.61–0.75) for BPH risk. Estimates of the PAF indicated that 9.1% (95% CI 5.8–12.5%) of BPH cases would be prevented if all individuals had adopted all five low‐risk sleep traits, assuming causality. Conclusions: Our study indicates an association between a healthy sleep pattern and a lower risk of BPH, emphasizing the importance of adhering to such patterns for potentially reducing BPH risk. Geriatr Gerontol Int 2024; 24: 675–682. [ABSTRACT FROM AUTHOR]

The UK Biobank (UKB) is a large cohort study that recruited over 500,000 British participants aged 40–69 in 2006–2010 at 22 assessment centers from across the United Kingdom. Self-reported health outcomes and hospital admission data are 2 types of records that include participants' disease status. Coronary artery disease (CAD) is the most common cause of death in the UKB cohort. After distinguishing between prevalence and incidence CAD events for all UKB participants, we identified geographical variations in age-standardized rates of CAD between assessment centers. Significant distributional differences were found between the pooled cohort equation scores of UKB participants from England and Scotland using the Mann–Whitney test. Polygenic risk scores of UKB participants from England and Scotland and from different assessment centers differed significantly using permutation tests. Our aim was to discriminate between assessment centers with different disease rates by collecting data on disease-related risk factors. However, relying solely on individual-level predictions and averaging them to obtain group-level predictions proved ineffective, particularly due to the presence of correlated covariates resulting from participation bias. By using the Mundlak model, which estimates a random effects regression by including the group means of the independent variables in the model, we effectively addressed these issues. In addition, we designed a simulation experiment to demonstrate the functionality of the Mundlak model. Our findings have applications in public health funding and strategy, as our approach can be used to predict case rates in the future, as both population structure and lifestyle changes are uncertain. [ABSTRACT FROM AUTHOR]

Background: While dietary salt intake has been linked with gastric cancer risk in Asian studies, findings from Western populations are sparse and limited to case—control studies. Our aim was to evaluate the frequency of adding salt to food at table in relation to gastric cancer risk among UK adults. Methods: We evaluated associations between the frequency of adding salt to food and the risk of gastric cancer in the UK Biobank (N = 471,144) using multivariable Cox regression. Frequency of adding salt to food was obtained from a touchscreen questionnaire completed at baseline (2006–2010). 24-h urinary sodium excretion was estimated using INTERSALT formulae. Cancer incidence was obtained by linkage to national cancer registries. Results: During a median follow-up period of 10.9 years, 640 gastric cancer cases were recorded. In multivariable models, the gastric cancer risk among participants reporting adding salt to food at table "always" compared to those who responded "never/rarely" was HR = 1.41 (95% CI: 1.04, 1.90). There was a positive linear association between estimated 24-h urinary sodium levels and the frequency of adding salt to food (p-trend <0.001). However, no significant association between estimated 24-h urinary sodium with gastric cancer was observed (HR = 1.19 (95% CI: 0.87, 1.61)). Conclusions: "Always adding salt to food" at table was associated with a higher gastric cancer risk in a large sample of UK adults. High frequency of adding salt to food at table can potentially serve as a useful indicator of salt intake for surveillance purposes and a basis for devising easy-to-understand public health messages. [ABSTRACT FROM AUTHOR]

Objective: To assess perinatal cardiac function in offspring of women with previous bariatric surgery and examine its association with maternal glucose control. Design: Prospective study. Setting: Maternity unit, UK. Population: Fifty‐four fetuses/neonates; 29 of post‐bariatric surgery women and 25 of women without surgery. Methods: Prospective, longitudinal observational study of pregnant women with and without previous bariatric surgery, matched for early pregnancy body mass index. Cardiac function of all offspring was assessed by two‐dimensional conventional, spectral tissue Doppler and speckle‐tracking echocardiography at 35–37 weeks of gestation and at 5–7 weeks of age. Maternal glycated haemoglobin (HbA1c) was measured at 27–30 weeks of gestation. Maternal demographics and fetal/infant cardiac function indices were compared between the groups. Correlation coefficient (r) is reported. Main outcome measures: Fetal/infant cardiac function indices. Results: Compared with no‐bariatric neonates, offspring of post‐bariatric women were smaller at birth (birthweight centiles: 64.96 ± 36.41 versus 40.17 ± 27.99; p = 0.007). There were no significant differences in fetal/infant cardiac function indices and perinatal cardiac changes, between groups. There was a positive correlation between maternal HbA1c and fetal left ventricular (LV) longitudinal strain (r = 0.33) and LV longitudinal strain rate (r = 0.29), suggesting an inverse relation between HbA1c and fetal LV systolic function, but this was mainly seen in offspring of women with no previous bariatric surgery (r = 0.56 and r = 0.50, respectively). Conclusions: Maternal bariatric surgery does not appear to inadvertently affect the offspring cardiac performance. We found an inverse correlation between maternal HbA1c levels and fetal LV systolic function but this was mainly seen in the no‐bariatric pregnancies. [ABSTRACT FROM AUTHOR]

Aim: To investigate the association between cardiovascular health metrics defined by Life's Essential 8 (LE8) scores and vascular complications among individuals with type 2 diabetes (T2D). Materials and Methods: This prospective study included 11 033 participants with T2D, all devoid of macrovascular diseases (including cardiovascular and peripheral artery disease) and microvascular complications (e.g. diabetic retinopathy, neuropathy and nephropathy) at baseline from the UK Biobank. The LE8 score comprised eight metrics: smoking, body mass index, physical activity, non‐high‐density lipoprotein cholesterol, blood pressure, glycated haemoglobin, diet and sleep duration. Cox proportional hazards models were established to assess the associations of LE8 scores with incident macrovascular and microvascular complications. Results: During a median follow‐up of 12.1 years, we identified 1975 cases of incident macrovascular diseases and 1797 cases of incident microvascular complications. After adjusting for potential confounders, each 10‐point increase in the LE8 score was associated with an 18% lower risk of macrovascular diseases and a 15% lower risk of microvascular complications. Comparing individuals in the highest and lowest quartiles of LE8 scores revealed hazard ratios of 0.55 (95% confidence interval 0.47‐0.62) for incident macrovascular diseases, and 0.61 (95% confidence interval 0.53‐0.70) for incident microvascular complications. This association remained robust across a series of sensitivity analyses and nearly all subgroups. Conclusion: Higher LE8 scores were associated with a lower risk of incident macrovascular and microvascular complications among individuals with T2D. These findings underscore the significance of adopting fundamental strategies to maintain optimal cardiovascular health and curtail the risk of developing diabetic vascular complications. [ABSTRACT FROM AUTHOR]

Introduction: Tailoring physical activity interventions to individual chronotypes and preferences by time of day could promote more effective and sustainable behavior change; however, our understanding of circadian physical behavior patterns is very limited. Objective: To characterize and compare 24‐h physical behavior patterns expressed relative to clock time (the standard measurement of time‐based on a 24‐h day) versus wake‐up time in a large British cohort age 46. Methods: Data were analyzed from 4979 participants in the age 46 sweep of the 1970 British Cohort Study who had valid activPAL accelerometer data across ≥4 days. Average steps and upright time (time standing plus time stepping) per 30‐min interval were determined for weekdays and weekends, both in clock time and synchronized to individual wake‐up times. Results: The mean weekday steps were 9588, and the mean weekend steps were 9354. The mean weekday upright time was 6.6 h, and the mean weekend upright time was 6.4 h. When synchronized to wake‐up time, steps peaked 1 h after waking on weekdays and 2.5 h after waking on weekends. Upright time peaked immediately, in the first 30‐min window, after waking on both weekdays and weekends. Conclusions: Aligning accelerometer data to wake‐up times revealed distinct peaks in stepping and upright times shortly after waking. Activity built up more gradually across clock time in the mornings, especially on weekends. Synchronizing against wake‐up times highlighted the importance of circadian rhythms and personal schedules in understanding population 24‐h physical behavior patterns, and this may have important implications for promoting more effective and sustainable behavior change. [ABSTRACT FROM AUTHOR]

Background and aims: Understanding the amounts of intensity-specific movement needed to attenuate the association between sedentary time and mortality may help to inform personalized prescription and behavioral counselling. Herein, we examined the joint associations of sedentary time and intensity-specific physical activity with all-cause and cardiovascular disease (CVD) mortality. Methods: Prospective cohort study including 73,729 adults from the UK Biobank who wore an Axivity AX3 accelerometer on their dominant wrist for at least 3 days, being one a weekend day, between June 2013 and December 2015. We considered the median tertile values of sedentary time and physical activity in each intensity band to determine the amount of physical activity needed to attenuate the association between sedentary time and mortality. Results: During a median of 6.9 years of follow-up (628,807 person-years), we documented 1521 deaths, including 388 from CVD. Physical activity of any intensity attenuated the detrimental association of sedentary time with mortality. Overall, at least a median of 6 min/day of vigorous physical activity, 30 min/day of MVPA, 64 min/day of moderate physical activity, or 163 min/day of light physical activity (mutually-adjusted for other intensities) attenuated the association between sedentary time and mortality. High sedentary time was associated with higher risk of CVD mortality only among participants with low MVPA (HR 1.96; 95% CI 1.23 to 3.14). Conclusions: Different amounts of each physical activity intensity may attenuate the association between high sedentary time and mortality. [ABSTRACT FROM AUTHOR]

Strongyloidiasis is a helminth infection where symptoms vary, and asymptomatic presentation is common. Chronic strongyloidiasis can cause a high mortality 'hyper-infection' in immunocompromised states. Understand- ing at risk populations and symptomology can guide screening and early treatment to reduce hyper-infection risk. A systematic review of studies describing patients in the UK with strongyloidiasis pooled a total of 1,308 patients. Weighted pooled prevalence (WPP) of asymptomatic cases was 27.7% (95% CI 17.1-39.5%, I² = 92%, p < 0.01). At-risk populations included migrants, returning travellers and armed forces personnel. The most common symptoms reported were abdominal pain (WPP 32.1% (95% CI 20.5-44.8%), I² = 93%, p < 0.01), rashes (WPP 38.4% (95% CI 13.1-67.7%), I² = 99%, p < 0.01) and diarrhoea (WPP 12.6% (95% CI 6.7-19.9%), I² =70%, p = 0.03). Symptomatology varied with cohort characteristics. Although asymptomatic presentation is common, patients may present with abdominal pain, diarrhoea or rashes. A low threshold for screening symptomatic individuals in at-risk groups is required. [ABSTRACT FROM AUTHOR]

We explored the early impact of changes to the UK alcohol tax system, implemented in August 2023, on the strength and price of alcoholic products available for sale on the website of the largest supermarket in England. Our comparative descriptive study using longitudinal brand-level data was not preregistered and should be considered exploratory. Data were collected weekly (May to October 2023) using automated web scraping tools. Outcomes were product strength (% alcohol by volume [ABV]) and price (per 10 mL of pure alcohol and per litre of product). We undertook paired t -tests, two-sample Kolmogorov–Smirnov tests, and quantile regression to compare outcomes before and after the tax changes. Beer, cider, spirits, and ready-to-drinks (RTDs) were analysed separately. There was a reduction in the mean strength of beer, driven by manufacturers reformulating a small number of weaker beers, moving them into a lower tax band (<3.5%ABV). The mean price per 10 mL of alcohol and per litre of product was significantly higher after the new tax system for beer, cider, and spirits and significantly lower for RTDs. Increases in the price of beer tended to occur across the entire distribution, whereas increases in the price of cider occurred among more expensive products. Changes to product strength tended to occur among weaker products near the new lowest tax band, suggesting tax bands may be a potential stimulus for change. Reformulation of stronger products would have better public health potential. Longer term monitoring, including data on purchasing/consumption, is required. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank. METHODS: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 years). RESULTS: A total of 25,697 participants (5.1%) had a history of IBS at baseline. After a median follow-up of 13.7 years, a total of 44,499 deaths occurred. Having an IBS diagnosis was strongly associated with lower risks of all-cause (HR50.70,95%CI50.62-0.78) and all-cancer (HR50.69,95%CI50.60-0.79) mortality in the first 5 years of follow-up. These associations were attenuated over follow-up, but even after 10 years of follow-up, associations remained inverse (all-cause: HR5 0.89, 95%CI5 0.84-0.96; all-cancer: HR 5 0.87, 95% CI 5 0.78-0.97) after full adjustment. Individuals with IBS had decreased risk of mortality from breast, prostate, and colorectal cancers in some of the follow-up time categories. DISCUSSION: We found that earlier during follow-up, having diagnosed IBS was associated with lower mortality risk, and the association attenuated over time. Additional studies to understand whether specific factors, such as lifestyle and healthcare access, explain the inverse association between IBS and mortality are needed. [ABSTRACT FROM AUTHOR]