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Objectives The impact of autoantibody profiles on the prognosis for idiopathic inflammatory myositis–associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with myositis-specific antibodies (MSAs) remains unclear. This retrospective cohort study examined whether serological profiles were associated with mortality or longitudinal lung function change. Methods The baseline clinical/demographic characteristics and follow-up lung function data of consecutive adult patients with IIM-ILD or interstitial pneumonia with autoimmune features (IPAF) positive for MSAs (IPAF-MSA) were extracted from three hospitals. Univariate and multivariate Cox proportional hazards analyses were used to compare mortality between groups of patients with different autoantibodies. Regression models were used to analyse their lung function trends. Results Of the 430 included patients, 81% met the IIM criteria, and the remaining 19% were diagnosed with IPAF-MSA. On univariate analysis, the risk factors associated with mortality included higher age, Charlson Comorbidity Index, and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared with anti-MDA5 negativity, anti-MDA5 positivity (MDA5+) was associated with higher mortality in the first 3 months [hazard ratio (HR) 65.2, 95% CI 14.1, 302.0], while no significant difference was seen thereafter (HR 0.55, 95% CI 0.14, 2.28). On multivariate analysis, combined anti-synthetase antibodies were associated with a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in patients with anti-Jo1+ (HR 0.61, 95% CI 0.4–0.87) and increased in patients with anti-PL7+ (HR 2.07, 95% CI 1.44–2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. Conclusion Among the autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ conferred higher mortality risks in patients with IIM-ILD. Survivors of an early peak of mortality in anti-MDA5+ disease appeared to have a favourable prognosis. [ABSTRACT FROM AUTHOR]

Background: Sedentary behavior (SB) has emerged as a significant health concern that deserves attention. This study aimed to examine the associations between prolonged sedentary behavior and the risk of all-cause and cause-specific mortality as well as to explore desirable alternatives to sitting in terms of physical activity (PA). Methods: Two prospective cohort investigations were conducted using the UK Biobank and NHANES datasets, with a total of 490,659 and 33,534 participants, respectively. Cox proportional hazards regression models were used to estimate the associations between SB and the risk of all-cause and cause-specific mortality due to cancer, cardiovascular disease (CVD), respiratory diseases, and digestive diseases. In addition, we employed isotemporal substitution models to examine the protective effect of replacing sitting with various forms of PA. Results: During the average follow-up times of 13.5 and 6.7 years, 36,109 and 3057 deaths were documented in the UK Biobank and NHANES, respectively. Both cohorts demonstrated that, compared with individuals sitting less than 5 h per day, individuals with longer periods of sitting had higher risks of all-cause and cause-specific mortality due to cancer, CVD, and respiratory diseases but not digestive diseases. Moreover, replacing SB per day with PA, even substituting 30 min of walking for pleasure, reduced the risk of all-cause mortality by 3.5% (hazard ratio [HR] 0.965, 95% confidence interval [CI] 0.954–0.977), whereas cause-specific mortality from cancer, CVD, and respiratory diseases was reduced by 1.6% (HR 0.984, 95% CI 0.968–1.000), 4.4% (HR 0.956, 95% CI 0.930–0.982), and 15.5% (HR 0.845, 95% CI 0.795–0.899), respectively. Furthermore, the protective effects of substitution became more pronounced as the intensity of exercise increased or the alternative duration was extended to 1 h. Conclusions: SB was significantly correlated with substantially increased risks of all-cause mortality and cause-specific mortality from cancer, CVD, and respiratory diseases. However, substituting sitting with various forms of PA, even for short periods involving relatively light and relaxing physical activity, effectively reduced the risk of both overall and cause-specific mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Though observational studies have widely linked air pollution exposure to various chronic diseases, evidence comparing different exposures in the same people is limited. This study examined associations between changes in air pollution exposure due to relocation and the incidence and mortality of 14 major diseases. METHODS: We included 50,522 participants enrolled in the UK Biobank from 2006 to 2010. Exposures to particulate matter with a diameter = 2.5μ m (PM2.5), particulate matter with a diameter = 10μ m (PM10), nitrogen oxides (NOx), nitrogen dioxide (NO2), and sulfur dioxide (SO2) were estimated for each participant based on their residential address and relocation experience during the follow-up. Nine exposure groups were classified based on changes in long-term exposures due to residential mobility. Incidence and mortality of 14 major diseases were identified through linkages to hospital inpatient records and death registries. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incidence and mortality of the 14 diseases of interest. RESULTS: During a median follow-up of 12.6 years, 29,869 participants were diagnosed with any disease of interest, and 3,144 died. Significantly increased risk of disease and all-cause mortality was observed among individuals who moved from a lower to higher air polluted area. Compared with constantly low exposure, moving from low to moderate PM2.5 exposure was associated with increased risk of all 14 diseases but not for all-cause mortality, with adjusted HRs (95% CIs) ranging from 1.18 (1.05, 1.33) to 1.48 (1.30, 1.69); moving from low to high PM2.5 areas increased risk of all 14 diseases: infections [1.37 (1.19, 1.58)], blood diseases [1.57 (1.34, 1.84)], endocrine diseases [1.77 (1.50, 2.09)], mental and behavioral disorders [1.93 (1.68, 2.21)], nervous system diseases [1.51 (1.32, 1.74)], ocular diseases [1.76 (1.56, 1.98)], ear disorders [1.58 (1.35, 1.86)], circulatory diseases [1.59 (1.42, 1.78)], respiratory diseases [1.51 (1.33, 1.72)], digestive diseases [1.74 (1.58, 1.92)], skin diseases [1.39 (1.22, 1.58)], musculoskeletal diseases [1.62 (1.45, 1.81)], genitourinary diseases [1.54 (1.36, 1.74)] and cancer [1.42 (1.24, 1.63)]. We observed similar associations for PM10 and SO2 with 14 diseases (but not with all-cause mortality); increases in NO2 and NOx were positively associated with 14 diseases and all-cause mortality. CONCLUSIONS: This study supports potential associations between ambient air pollution exposure and morbidity as well as mortality. Findings also emphasize the importance of maintaining consistently low levels of air pollution to protect the public’s health [ABSTRACT FROM AUTHOR]

Aims: The direct cost of diabetes to the UK health system was estimated at around £10 billion in 2012. This analysis updates that estimate using more recent and accurate data sources. Methods: A pragmatic review of relevant data sources for UK nations was conducted, including population‐level data sets and published literature, to generate estimates of costs separately for Type 1, Type 2 and gestational diabetes. A comprehensive cost framework, developed in collaboration with experts, was used to create a population‐based cost of illness model. The key driver of the analysis was prevalence of diabetes and its complications. Estimates were made of the excess costs of diagnosis, treatment and diabetes‐related complications compared with the general UK population. Estimates of the indirect costs of diabetes focused on productivity losses due to absenteeism and premature mortality. Results: The direct costs of diabetes in 2021/22 for the UK were estimated at £10.7 billion, of which just over 40% related to diagnosis and treatment, with the rest relating to the excess costs of complications. Indirect costs were estimated at £3.3 billion. Conclusions: Diabetes remains a considerable cost burden in the UK, and the majority of those costs are still spent on potentially preventable complications. Although rates of some complications are reducing, prevalence continues to increase and effective approaches to primary and secondary prevention continue to be needed. Improvements in data capture, data quality and reporting, and further research on the human and financial implications of increasing incidence of Type 2 diabetes in younger people are recommended. [ABSTRACT FROM AUTHOR]

Background: It remains unknown how the patterns of change of social isolation and loneliness are associated with the onset of cardiovascular disease (CVD) and mortality. We aimed to investigate the longitudinal association of changes in social isolation and loneliness with incident CVD, all-cause mortality, CVD mortality and subsequent cardiac function. Methods: This prospective cohort study included 18,258 participants aged 38–73 years who participated in visit 0 (2006–2010) and visit 1 (2012–2013) using UK Biobank (mean age 57.1, standard deviation [SD] 7.4; 48.7% males). Social isolation or loneliness was categorized into four patterns: never, transient, incident, and persistent. Incident CVD, all-cause and CVD mortality were ascertained through linkage data. Cardiac function was assessed by cardiovascular magnetic resonance imaging in a subsample (N = 5188; visit 2, since 2014). Results: Over a median follow-up of 8.3 (interquartile range [IQR] 8.1–8.6) years, compared with never social isolation, persistent social isolation was associated with the higher risk of incident CVD (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.03–1.33), all-cause (1.42, 1.12–1.81) and CVD (1.53, 1.05–2.23) mortality. Likewise, persistent loneliness was strongly associated with the greater risk of incident CVD (1.13, 1.00–1.27), all-cause (1.28, 1.02–1.61) and CVD mortality (1.52, 1.06–2.18). Conclusions: Persistent social isolation and loneliness posed a substantially higher risk for incident CVD, all-cause and CVD mortality, and cardiac dysfunction than other patterns. Persistent social isolation and loneliness, along with an increasing cumulative score, are associated with lower cardiac function. [ABSTRACT FROM AUTHOR]

Previous studies only focused on the individual social factors, without considering the overall social health patterns. The present study aimed to develop an integrated social health score (SHS) and investigate its associations with all-cause, cardiovascular disease (CVD), cancer mortality. A total of 330,716 participants (mean age 56.3 years; 52.4 % female) from UK Biobank was included between 2006 and 2010, and thereafter followed up to 2021. SHS was calculated by using information on social connections, social engagement and social support. Cox proportional hazards models was used to estimate the hazard ratios and 95 % confidence intervals (CIs) of the association between SHS and all-cause and cause-specific mortality and the 4-way decomposition was used to quantify the mediating effect of lifestyle factors. During a median follow-up period of 12.4 years, 37,897 death cases were recorded, including 4347 CVD and 10,380 cancer cases. The SHS was inversely associated with the risks of all-cause, CVD and cancer mortality in a dose-dependent manner (P for trend <0.001). The association between SHS with all-cause mortality was mediated by lifestyle factors including diet score, smoking status and alcohol consumption. Integrated SHS was inversely associated with risks of all-cause, CVD and cancer mortality, and the associations were partially mediated by lifestyle factors. Our study highlights the importance of maintaining high levels of social health by jointly enhancing social involvement, expanding social networks, and cultivating enduring intimate relationships across the life course. • The social health score was calculated based on information about social connections, engagement, and support, indicting better social health with higher scores. • Social health score was inversely associated with risks of all-cause, CVD and cancer mortality. • The association between social health score with all-cause mortality was mediated by lifestyle factors, including diet score, smoking status, and alcohol consumption. [ABSTRACT FROM AUTHOR]

Rationale: Despite evidence demonstrating a prognostic role for computed tomography (CT) scans in idiopathic pulmonary fibrosis (IPF), image-based biomarkers are not routinely used in clinical practice or trials. Objectives: To develop automated imaging biomarkers using deep learning–based segmentation of CT scans. Methods: We developed segmentation processes for four anatomical biomarkers, which were applied to a unique cohort of treatment-naive patients with IPF enrolled in the PROFILE (Prospective Observation of Fibrosis in the Lung Clinical Endpoints) study and tested against a further United Kingdom cohort. The relationships among CT biomarkers, lung function, disease progression, and mortality were assessed. Measurements and Main Results: Data from 446 PROFILE patients were analyzed. Median follow-up duration was 39.1 months (interquartile range, 18.1–66.4 mo), with a cumulative incidence of death of 277 (62.1%) over 5 years. Segmentation was successful on 97.8% of all scans, across multiple imaging vendors, at slice thicknesses of 0.5–5 mm. Of four segmentations, lung volume showed the strongest correlation with FVC (r = 0.82; P < 0.001). Lung, vascular, and fibrosis volumes were consistently associated across cohorts with differential 5-year survival, which persisted after adjustment for baseline gender, age, and physiology score. Lower lung volume (hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.96–0.99]; P = 0.001), increased vascular volume (HR, 1.30 [95% CI, 1.12–1.51]; P = 0.001), and increased fibrosis volume (HR, 1.17 [95% CI, 1.12–1.22]; P < 0.001) were associated with reduced 2-year progression-free survival in the pooled PROFILE cohort. Longitudinally, decreasing lung volume (HR, 3.41 [95% CI, 1.36–8.54]; P = 0.009) and increasing fibrosis volume (HR, 2.23 [95% CI, 1.22–4.08]; P = 0.009) were associated with differential survival. Conclusions: Automated models can rapidly segment IPF CT scans, providing prognostic near and long-term information, which could be used in routine clinical practice or as key trial endpoints. [ABSTRACT FROM AUTHOR]

Background and Aims: Primary biliary cholangitis (PBC) is a chronic, immune‐mediated liver disease that can lead to fibrosis and cirrhosis. In this cohort study, we aimed to investigate morbidity and mortality in conjunction with metabolomic changes of PBC in a UK population‐based cohort. Methods: 454 participants with PBC and 908 propensity score (age, sex, BMI, ethnicity) matched controls without liver disease were included in the study. A subset of participants with PBC and controls were analysed for their metabolomic profile. Further, PBC‐associated comorbidities were investigated by PheWAS analysis. Lastly, we assessed causes of death in individuals with PBC using a Fine and Grey competing‐risks regression model. Results: Compared to the control group, various pathways associated with the metabolism of amino acids, lipids, and liver biochemistry were significantly enriched in individuals with PBC. We found reduced levels of S‐HDL‐cholesterol and Glycoprotein Acetyls in individuals with PBC as well as an association with diseases of the circulatory system. Notably, PBC individuals had a higher prevalence of digestive diseases, autoimmune diseases, cardiovascular diseases, anaemias, mental disorders, and urinary tract infections compared to the control group. Strikingly, the overall mortality was almost three times higher in the PBC group compared to the control group, with diseases of the digestive system accounting for a significant elevation of the death rate. A subsequent analysis, enhanced by propensity score matching that included the APRI score, demonstrated that the observed morbidity could not be exclusively attributed to advanced hepatic disease. Conclusions: Our study provides a detailed perspective on the morbidity of individuals with PBC. The exploration of potential effects of disease state on morbidity suggest that early detection and early treatment of PBC could enhance patient prognosis and prevent the onset of comorbid diseases. Finally, the metabolomic alterations could represent a link between the pathophysiological processes underlying PBC development, progression, and associated morbidity. [ABSTRACT FROM AUTHOR]

Livestreaming and filming death rites and funeral ceremonies to enable remote engagement proliferated rapidly during the COVID-19 pandemic, and many expect these options to remain prevalent going forward. This paper draws on interviews with a diverse UK sample of 68 bereaved people, funeral directors, officiants and celebrants. It illustrates how, and explains why, people's experiences and evaluations of hybrid funerals can vary. In a context when in-person gatherings were limited, hybridisation played a valuable role in enabling more people to engage with funerals. However, virtual attendance was often considered less satisfying than in-person attendance because it did not enable people to participate well in the funeral activities that mattered to them or to participate with others as they would in person. Scope for participation was partly contingent on the functionality and use made of technology, including whether and which steps were taken to facilitate engagement and a sense of connection for those joining online. People's evaluations of hybrid funerals could also reflect their relationships to the deceased and their frames of reference – for example, whether they were comparing virtual attendance to attending in person, or to being unable to attend at all, or to an overwhelmingly large funeral. [ABSTRACT FROM AUTHOR]

Background: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. Methods: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. Results: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. Conclusions: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Metabolomic age models have been proposed for the study of biological aging, however, they have not been widely validated. We aimed to assess the performance of newly developed and existing nuclear magnetic resonance spectroscopy (NMR) metabolomic age models for prediction of chronological age (CA), mortality, and age‐related disease. Ninety‐eight metabolic variables were measured in blood from nine UK and Finnish cohort studies (N ≈31,000 individuals, age range 24–86 years). We used nonlinear and penalized regression to model CA and time to all‐cause mortality. We examined associations of four new and two previously published metabolomic age models, with aging risk factors and phenotypes. Within the UK Biobank (N ≈102,000), we tested prediction of CA, incident disease (cardiovascular disease (CVD), type‐2 diabetes mellitus, cancer, dementia, and chronic obstructive pulmonary disease), and all‐cause mortality. Seven‐fold cross‐validated Pearson's r between metabolomic age models and CA ranged between 0.47 and 0.65 in the training cohort set (mean absolute error: 8–9 years). Metabolomic age models, adjusted for CA, were associated with C‐reactive protein, and inversely associated with glomerular filtration rate. Positively associated risk factors included obesity, diabetes, smoking, and physical inactivity. In UK Biobank, correlations of metabolomic age with CA were modest (r = 0.29–0.33), yet all metabolomic model scores predicted mortality (hazard ratios of 1.01 to 1.06/metabolomic age year) and CVD, after adjustment for CA. While metabolomic age models were only moderately associated with CA in an independent population, they provided additional prediction of morbidity and mortality over CA itself, suggesting their wider applicability. [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]

Neuromyelitis optica spectrum disorder is an autoimmune disease, causing severe disability due to relapses, but recent mortality data are limited. Among 396 patients seropositive for anti‐aquaporin‐4 antibody from 2014 to 2020 in the United Kingdom, 39 deaths occurred: 19 (48.7%) were unrelated to disease; 14 (35.9%) were severe disability‐ or relapse‐related; and 4 (10.3%) were attributed to malignancy/infection. Mean annual mortality was 1.92% versus 0.63% in the matched population. The standardized mortality ratio was 3.04 (95% confidence interval 1.67–5.30) with 1.29% excess mortality per year in patients. Median Expanded Disability Status Scale before death was 7.0. Results highlight the importance of preventing relapses that drive disability. [ABSTRACT FROM AUTHOR]

Aims Disruption of the predictable symmetry of the healthy heart may be an indicator of cardiovascular risk. This study defines the population distribution of ventricular asymmetry and its relationships across a range of prevalent and incident cardiorespiratory diseases. Methods and results The analysis includes 44 796 UK Biobank participants (average age 64.1 ± 7.7 years; 51.9% women). Cardiovascular magnetic resonance (CMR) metrics were derived using previously validated automated pipelines. Ventricular asymmetry was expressed as the ratio of left and right ventricular (LV and RV) end-diastolic volumes. Clinical outcomes were defined through linked health records. Incident events were those occurring for the first time after imaging, longitudinally tracked over an average follow-up time of 4.75 ± 1.52 years. The normal range for ventricular symmetry was defined in a healthy subset. Participants with values outside the 5th-95th percentiles of the healthy distribution were classed as either LV dominant (LV/RV > 112%) or RV dominant (LV/RV < 80%) asymmetry. Associations of LV and RV dominant asymmetry with vascular risk factors, CMR features, and prevalent and incident cardiovascular diseases (CVDs) were examined using regression models, adjusting for vascular risk factors, prevalent diseases, and conventional CMR measures. Left ventricular dominance was linked to an array of pre-existing vascular risk factors and CVDs, and a two-fold increased risk of incident heart failure, non-ischaemic cardiomyopathies, and left-sided valvular disorders. Right ventricular dominance was associated with an elevated risk of all-cause mortality. Conclusion Ventricular asymmetry has clinical utility for cardiovascular risk assessment, providing information that is incremental to traditional risk factors and conventional CMR metrics. [ABSTRACT FROM AUTHOR]

Background: Frailty is a clinical state that increases susceptibility to minor stressor events. The risk of frailty is higher in chronic conditions, such as Chronic Obstructive Pulmonary Disease (COPD). Recent studies on COPD have shown that patients living with frailty have an increased risk of mortality. The presence of cardiovascular diseases or conditions are common in COPD and may increase the risk of death. Methods: This protocol describes a European prospective cohort study of community-based people, in a stable condition with diagnosis of COPD (as defined by GOLD guidelines) across hospitals in Italy and UK. Frailty prevalence will be assessed using the Clinical Frailty Scale. At 1- and 2-year follow up, primary outcome will be the impact of frailty on the number of cardiovascular events; secondary outcomes: the influence of frailty on cardiovascular mortality, all-cause mortality, and deaths due to COPD. For the primary outcome a zero-inflated Poisson regression will compare the number of cardiovascular events at 1 year. Secondary outcomes will be analysed using the time to mortality. Discussion: This multicentre study will assess the association between frailty and cardiovascular events and mortality in population with COPD. Data collection is prospective and includes routine clinical data. This research will have important implications for the management of patients with COPD to improve their quality of care, and potentially prognosis. Trial registration number: NCT05922202 (www.clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Physical activity (PA) has been shown to reduce diabetes mortality, but largely based on imprecise self-reported data, which may hinder the development of related recommendations. Here, we perform a prospective cohort study of 19,624 individuals with type 2 diabetes (T2D) from the UK Biobank with a median follow-up of 6.9 years. Duration and intensity of PA are measured by wrist-worn accelerometers over a 7-day period. We observe L-shaped associations of longer duration of PA, regardless of PA intensity, with risks of all-cause and cancer mortality, as well as a negatively linear association with cardiovascular disease mortality. 12.7%, 15.8%, and 22.3% of deaths are attributable to the lowest level of light-intensity, moderate-intensity PA, and vigorous-intensity PA, respectively. Collectively, our findings provide insights for clinical guidelines that should highlight the potential value of adherence to greater intensity and duration of PA for patients with T2D. Physical activity is ameliorative for individuals with type 2 diabetes, but most previous studies have relied on self-reported data, which are subject to recall bias. Here, the authors show L-shaped associations of accelerometer-derived physical activity with all-cause mortality, and a negative linear association with cardiovascular disease mortality in diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Small airways obstruction (SAO) has been associated with occupational exposures. Whether exposure to harmful occupational agents impacts the survival of people with SAO is unknown. Our aim was to estimate the mortality risk associated with occupational exposures among people with SAO. Methods: We used data from UK Biobank participants with SAO, defined as a ratio of forced expiratory volume in three seconds to forced expiratory volume in six seconds (FEV3/FEV6) below the lower limit of normal. We assigned lifetime occupational exposures to participants with available occupational histories using the ALOHA+ Job Exposure Matrix. Mortality data were provided by the National Death Registries. We used Cox regression to assess the association of all-cause mortality with lifetime occupational exposures (vapours, gases, dusts, fumes—VGDF; solvents; pesticides; metals), adjusting for potential confounders. Results: The 13,942 participants with SAO had a mean age of 56±7 years, 59% were females and 94.2% were of White ancestry. Overall, there were 457 deaths over a median follow-up of 12.8 years. A greater mortality risk was associated with exposure to VGDF, with hazard ratios of 1.32 (95%CI: 1.04–1.78) for low levels and 1.41 (95%CI: 1.11–1.78) for moderate levels of cumulative exposure. There was no evidence of association for the other occupational exposures. Conclusion: Lifetime occupational exposure to VGDF in people with SAO may have a detrimental effect on their survival. Future respiratory health surveillance programmes of people exposed to VGDF should consider assessment for SAO and focus on primary prevention through adequate exposure control. [ABSTRACT FROM AUTHOR]

Background Sarcopenia has been identified as a risk factor for increased mortality in individuals with CKD. However, when considering individuals with mild kidney dysfunction prior to CKD, the impact of sarcopenia on adverse outcomes, particularly mortality, remains uncertain. Methods This study included 323 801 participants from the UK Biobank. Mild kidney dysfunction was defined as estimated glomerular filtration rate between 60 and 89.9 mL/min/1.73 m2, and sarcopenia was defined according to the criteria of the 2019 European Working Group of Sarcopenia in Older People. Cox proportional hazard models with inverse probability weighting and competing risk models were used for analysis. Results During a median follow-up of 11.8 years, 20 146 participants died from all causes. Compared with participants with normal kidney function and without sarcopenia, those with mild kidney dysfunction or sarcopenia had significantly increased risks of all-cause mortality [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.12–1.19; HR 1.29, 95% CI 1.20–1.37]; those with both mild kidney dysfunction and sarcopenia had an even higher risk of all-cause mortality (HR 1.61, 95% CI 1.52–1.71), with a significant overall additive interaction (relative risk due to interaction 0.17, 95% CI 0.05–0.29). Further subgroup analyses revealed that the associations of probable sarcopenia with all-cause and cause-specific mortality (non-accidental cause, non-communicable diseases and cancer) were stronger among participants with mild kidney dysfunction than those with normal kidney function. Conclusions The study indicates that sarcopenia and mild kidney dysfunction synergistically increase the risk of all-cause and cause-specific mortality. Early recognition and improvement of mild kidney function or sarcopenia in older people may reduce mortality risk but would require more prospective confirmation. [ABSTRACT FROM AUTHOR]

Context: Epidemiological studies involving patients with acromegaly have yielded conflicting results regarding cancer incidence and causes of mortality in relation to control of growth hormone (GH) excess. Objective: The objective of this retrospective cohort study is to clarify these questions and identify goals for treatment and monitoring patients. Methods: We studied 1845 subjects from the UK Acromegaly Register (1970–2016), obtaining cancer standardised incidence rates (SIR) and all causes standardised mortality rates (SMR) from UK Office for National Statistics, to determine the relationship between causes of mortality—age at diagnosis, duration of disease, post‐treatment and mean GH levels. Results: We found an increased incidence of all cancers (SIR, 1.38; 95% CI: 1.06–1.33, p <.001), but no increase in incidence of female breast, thyroid, colon cancer or any measure of cancer mortality. All‐cause mortality rates were increased (SMR, 1.35; 95% CI: 1.24–1.46, p <.001), as were those due to vascular and respiratory diseases. All‐cause, all cancer and cardiovascular deaths were highest in the first 5 years following diagnosis. We found a positive association between post‐treatment and mean treatment GH levels and all‐cause mortality (p <.001 and p <.001), which normalised with posttreatment GH levels of <1.0 µg/L or meantreatment GH levels of <2.5 µg/L. Conclusion: Acromegaly is associated with increased incidence of all cancers but not thyroid or colon cancer and no increase in cancer mortality. Excess mortality is due to vascular and respiratory disease. The risk is highest in the first 5 years following diagnosis and is mitigated by normalising GH levels. [ABSTRACT FROM AUTHOR]

A population's current growth rate is determined jointly by changes in fertility, mortality, and migration. This overall growth rate is also the average of age-specific growth rates, which can be decomposed into the result of historical changes in fertility, mortality, and migration. However, doing so requires more than 100 years of historical data, meaning that such analyses are possible only in a select few populations. In this research note, we propose an adapted version of the variable-r model to measure contributions to the population growth rate for countries with shorter demographic series. In addition, we extend this model to explore the contribution of subnational changes to the national population growth rate. Our results demonstrate that the age-specific growth rates obtained from short historical series, say 25 years, closely match those of the longer series. These abbreviated age-specific growth rates closely resemble the growth rate at birth of their respective cohorts, which is the major determinant of population growth, except at older ages where mortality becomes the main explanatory element. Exploring subnational populations, we find considerable heterogeneity in the age profile of the components of growth and find that the most populous regions tend to have an outsized impact on national-level growth. [ABSTRACT FROM AUTHOR]

Background: Previous retrospective studies have shown a correlation between depression and increased risk of infections, including a moderate rise in sepsis likelihood associated with severe depression and anxiety. To investigate the potential causal links between depression, sepsis, and mortality risks, while considering confounding factors, we employed a Mendelian randomization (MR) approach. Methods: In this two-sample Mendelian randomization study, we analyzed data from a large-scale genome-wide association study on depression, involving 807,553 European individuals (246,363 cases, 561,190 controls). We extracted SNP associations with sepsis and 28-day mortality from UK Biobank GWAS outcomes. The correlation analysis primarily employed the inverse-variance weighted method, supplemented by sensitivity analyses for heterogeneity and pleiotropy assessment. Results: Our analysis revealed a potential causal link between depression and an increased risk of sepsis (OR = 1.246, 95% CI: 1.076–1.442, P = 0.003), but no causal association was found with sepsis-induced mortality risk (OR = 1.274, 95% CI: 0.891–1.823, P = 0.184). Sensitivity analyses confirmed the robustness of these findings. Conclusions: We identified a potential causal association between depression and heightened sepsis risk, while no link was found with sepsis-induced mortality. These findings suggest that effective management of depression could be important in preventing sepsis. [ABSTRACT FROM AUTHOR]

Background: Characterization of shared cancer mechanisms have been proposed to improve therapy strategies and prognosis. Here, we aimed to identify shared cell–cell interactions (CCIs) within the tumor microenvironment across multiple solid cancers and assess their association with cancer mortality. Methods: CCIs of each cancer were identified by NicheNet analysis of single-cell RNA sequencing data from breast, colon, liver, lung, and ovarian cancers. These CCIs were used to construct a shared multi-cellular tumor model (shared-MCTM) representing common CCIs across cancers. A gene signature was identified from the shared-MCTM and tested on the mRNA and protein level in two large independent cohorts: The Cancer Genome Atlas (TCGA, 9185 tumor samples and 727 controls across 22 cancers) and UK biobank (UKBB, 10,384 cancer patients and 5063 controls with proteomics data across 17 cancers). Cox proportional hazards models were used to evaluate the association of the signature with 10-year all-cause mortality, including sex-specific analysis. Results: A shared-MCTM was derived from five individual cancers. A shared gene signature was extracted from this shared-MCTM and the most prominent regulatory cell type, matrix cancer-associated fibroblast (mCAF). The signature exhibited significant expression changes in multiple cancers compared to controls at both mRNA and protein levels in two independent cohorts. Importantly, it was significantly associated with mortality in cancer patients in both cohorts. The highest hazard ratios were observed for brain cancer in TCGA (HR [95%CI] = 6.90[4.64–10.25]) and ovarian cancer in UKBB (5.53[2.08–8.80]). Sex-specific analysis revealed distinct risks, with a higher mortality risk associated with the protein signature score in males (2.41[1.97–2.96]) compared to females (1.84[1.44–2.37]). Conclusion: We identified a gene signature from a comprehensive shared-MCTM representing common CCIs across different cancers and revealed the regulatory role of mCAF in the tumor microenvironment. The pathogenic relevance of the gene signature was supported by differential expression and association with mortality on both mRNA and protein levels in two independent cohorts. [ABSTRACT FROM AUTHOR]

Objectives: To assess the impact of urinary incontinence (UI) on health outcomes over the entire spectrum of acute stroke severity (National Institutes of Health Stroke Scale [NIHSS] scores: 0–42), due to a paucity of data on patients with milder strokes. Patients and Methods: Data were prospectively collected (2014–2016) from the Sentinel Stroke National Audit Programme (1593 men, 1591 women; mean [SD] age 76.8 [13.3] years) admitted to four UK hyperacute stroke units (HASUs). Relationships between variables were assessed by multivariable logistic regression. Data were adjusted for age, sex, comorbidities, pre‐stroke disability and intra‐cranial haemorrhage, and presented as odds ratios with 95% confidence intervals. Results: Amongst patients with no symptoms or a minor stroke (NIHSS scores of 0–4), compared to patients without UI, patients with UI had significantly greater risks of poor outcomes including: in‐hospital mortality; disability at discharge; in‐hospital pneumonia; urinary tract infection within 7 days of admission; prolonged length of stay on the HASU; palliative care by discharge; activity of daily living (ADL) support, and new discharge to care home. In patients with more moderate stroke (NIHSS score of 5–15) the same outcomes were identified; being at greater risk for patients with UI, except for palliative care by discharge and ADL support. With the highest stroke severity group (NIHSS score of 16–48) all outcomes were identified except in‐patient mortality, pneumonia, and ADL support. However, odds ratios diminished as NIHSS scores increased. Conclusions: Urinary incontinence is a useful indicator of poor short‐term outcomes in older patients with an acute stroke, but irrespective of stroke severity. This provides valuable information to healthcare professionals to identify at‐risk individuals. [ABSTRACT FROM AUTHOR]

Purpose: There is a global trend of increased periprosthetic fractures due to the growing number of arthroplasty procedures. The present study assessed the impact of factors such as time to surgery and type of surgery on the outcomes, which have been seldom evaluated for periprosthetic fractures. Methods: An observational study was conducted on consecutive 87 patients within an NHS district hospital trust in the UK. Patients who underwent a complete hip replacement prior to the fracture, received fixation therapy, or underwent revision surgery within the specified time were screened. Patients were grouped in two ways: based on time to surgery and based on surgery type. Logistic regression models were performed to assess for statistically significant differences in post-operative complication, 30-day, and 1-year mortality rates between groups, whilst adjusting for age, gender, and ASA grade. Results: Forty-one patients underwent open reduction and internal fixation (ORIF), 29 patients underwent revision arthroplasty, and 17 patients were subjected to both, ORIF and revision arthroplasty. Sixty of the 87 patients were operated on > 48 h of injury. The median hospital stay was significantly lower in the ORIF plus revision arthroplasty group, versus other surgical groups (p < 0.05) whilst it was significantly higher in the group of patients who underwent surgery after 48 h of injury (p < 0.05). Numerically higher mortality was noted in the revision arthroplasty group (31.03%, p > 0.05). The group that was operated after 48 h of injury showed greater mortality but was comparable to the other group (25% vs. 14.81%, p > 0.05). For post-operative complications, none of the variables were significantly predictive (p > 0.05). However, for 30-day mortality, ASA grade (p = 0.04) and intra-operative complications (p = 0.0001) were significantly predictive. Additionally, for 1-year mortality, ASA grade (p = 0.004) was noted to be significantly predictive. Conclusion: Revision and delayed periprosthetic fracture management (> 48 h after injury) group showed a numerically greater mortality risk; however, this finding was not statistically significant. ASA grading at baseline is predictive of mortality for periprosthetic fractures. [ABSTRACT FROM AUTHOR]

Background: Meningoencephalitis of unknown origin (MUO) comprises a group of noninfectious inflammatory diseases affecting the central nervous system of dogs. Previous studies have reported individual risk factors for survival but prognostication for MUO remains challenging. Objectives: Identify clinical prognostic variables in dogs with MUO. Animals: A retrospective study of 447 dogs presented to 2 UK referral hospitals and diagnosed with MUO. Methods: Medical records of dogs diagnosed with MUO were retrospectively reviewed. Multivariable logistic regression was used for the identification of risk factors for survival and Cox proportional hazards analysis for the identification of risk factors for clinical relapse. Results: Eighty‐two percent (366/447) of dogs with presumptive MUO survived to discharge and 63.5% (284/447) were alive at 6 months; 36% of the latter (103/284) had persistent neurological deficits. Breed (pugs; P =.03), epileptic seizures (P <.001), paresis (P <.001), and higher neurodisability scale (NDS) score (P <.001) at presentation were negatively associated with survival to 6 months. Dogs with persistent deficits had higher NDS scores on presentation (P =.001). Median follow‐up time was 11 months (interquartile range [IQR], 1‐24) and 50.6% (160/316) relapsed during treatment (median time to relapse, 7 months; IQR, 2‐15). Incomplete resolution of the clinical signs during the 6 months after diagnosis (P <.001), higher NDS score (P <.001), and longer duration of the clinical signs (P <.001) were associated with relapse. Conclusions and Clinical Importance: Knowledge of risk factors associated with survival, incomplete recovery and clinical relapse in MUO can help guide monitoring and treatment and improve owner communications regarding prognosis for this debilitating disease. [ABSTRACT FROM AUTHOR]

Background: A third of people with epilepsy are drug resistant. People with drug-resistant epilepsy (DRE) have a higher risk of mortality and physical injuries than those who respond to anti-seizure medication (ASM). This study describes patient characteristics, comorbidities, and mortality in people with DRE in the UK. Methods: The Clinical Practice Research Datalink was utilised to select people with DRE prescribed a third ASM between 1 January 2011 and 31 March 2021. Annual incidence and prevalence of DRE, patient characteristics, comorbidities, and mortality rates were analysed. Subgroup analysis was performed by age, sex, presence of intellectual disabilities and time from epilepsy diagnosis to DRE. Results: A total of 34,647 people with DRE were included (mean ± SD age 42.68 ± 23.59 years, 52.6% females). During the study period, annual DRE incidence ranged from 1.99% to 3.12%. As of 31 March 2021, DRE prevalence was 26.6% (95% confidence interval [CI] 26.3%–26.8%). A greater proportion of people with DRE resided in the most deprived regions, with 21.1% and 16.7% in the top two quintiles of the Index of Multiple Deprivation respectively, compared to < 15% in the three less deprived regions. All-cause mortality ranged from 3,687 to 4,802 per 100,000 persons with DRE, four times higher than that in the general population in the UK. Variations existed across subgroups. Conclusions: Considerable disease burden was observed in people with DRE in the UK. The findings emphasise the importance of early DRE diagnosis and appropriate disease management in people who develop DRE. [ABSTRACT FROM AUTHOR]

Introduction: The delivery of COVID-19 vaccines was successful in reducing hospitalizations and mortality. However, emergence of the Omicron variant resulted in increased virus transmissibility. Consequently, booster vaccination programs were initiated to decrease the risk of severe disease and death among vulnerable members of the population. This study aimed to estimate the effects of the booster program and alternative vaccination strategies on morbidity and mortality due to COVID-19 in the UK. Method: A Susceptible-Exposed-Infectious-Recovered (SEIR) model was used to assess the impact of several vaccination strategies on severe outcomes associated with COVID-19, including hospitalizations, mortality, National Health Service (NHS) capacity quantified by hospital general ward and intensive care unit (ICU) bed days, and patient productivity. The model accounted for age-, risk- and immunity-based stratification of the UK population. Outcomes were evaluated over a 48-week time horizon from September 2022 to August 2023 considering the actual UK autumn 2022/spring 2023 booster campaigns and six counterfactual strategies. Results: The model estimated that the autumn 2022/spring 2023 booster campaign resulted in a reduction of 18,921 hospitalizations and 1463 deaths, compared with a no booster scenario. Utilization of hospital bed days due to COVID-19 decreased after the autumn 2022/spring 2023 booster campaign. Expanding the booster eligibility criteria and improving uptake improved all outcomes, including averting twice as many ICU admissions, preventing more than 20% additional deaths, and a sevenfold reduction in long COVID, compared with the autumn 2022/spring 2023 booster campaign. The number of productive days lost was reduced by fivefold indicating that vaccinating a wider population has a beneficial impact on the morbidities associated with COVID-19. Conclusion: Our modelling demonstrates that the autumn 2022/spring 2023 booster campaign reduced COVID-19-associated morbidity and mortality. Booster campaigns with alternative eligibility criteria warrant consideration in the UK, given their potential to further reduce morbidity and mortality as future variants emerge. [ABSTRACT FROM AUTHOR]

The potential influence of tinnitus on cardiovascular disease (CVD) and all-cause mortality has yet to be explored. We aim to examine the correlations between tinnitus and the risk of cardiovascular events and all-cause mortality. We conducted a prospective cohort study utilising data from the UK Biobank. The presence of tinnitus was evaluated through a questionnaire. The primary outcome was defined as a composition of cardiovascular events, including myocardial infarction (MI), stroke, and mortality from CVD, as well as all-cause mortality. Cox proportional hazard models were employed to examine the associations between tinnitus and both the primary outcome and its individual components. Sensitivity analyses were conducted to evaluate the robustness of the primary analysis. A total of 140,146 participants were included in the study. The presence of tinnitus was found to be associated with a higher incident rate of the primary outcome (HR = 1.057, 95%CI: 1.017–1.099, p = 0.005), MI (HR = 1.139, 95%CI: 1.061–1.222, p < 0.001) and all-cause mortality (HR = 1.053, 95%CI: 1.003–1.105, p = 0.038) after adjusting for confounders. However, there was no significant association between tinnitus and stroke or mortality from CVD. Subgroup analysis revealed that the association between tinnitus and the primary outcome was significant in females, participants with abnormal BMI, and those without hearing difficulty, depression or anxiety. Sensitivity analyses yielded consistent results. The findings from this study contribute to the existing body of evidence suggesting an association between tinnitus and an increased risk of cardiovascular events and all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Benzene affects human health through environmental exposure in addition to occupational contact. However, few studies have examined the associations between long-term exposure to low concentrations of ambient benzene and mortality risks in nonoccupational settings. Methods: This prospective cohort study consists of 393,042 participants without stroke, myocardial infarction, or cancer at baseline from the UK Biobank. Annual average concentrations of benzene for each year during follow-up were measured using air dispersion models. The main outcomes were all-cause mortality and mortality from specific causes. Cox proportional-hazards models with time-varying exposure measurements were used to estimate the hazard ratios and 95% confidence intervals (CIs) for mortality risks. Restricted cubic spline models were used to estimate exposure–response relationships. Measurements and Main Results: With each interquartile range increase in the average annual concentration of benzene, the adjusted hazard ratios of mortality risk from all causes, cardiovascular disease, cancer, and respiratory disease were 1.26 (95% CI, 1.24–1.27), 1.24 (95% CI, 1.21–1.28), 1.27 (95% CI, 1.25–1.29), and 1.25 (95% CI, 1.20–1.30), respectively. The monotonically increasing exposure–response curves showed no threshold and plateau within the observed concentration range. Furthermore, the effect of benzene exposure on mortality persisted across different subgroups and was somewhat stronger in younger and White people (P for interaction < 0.05). Conclusions: Long-term exposure to low concentrations of ambient benzene significantly increases mortality risk in the general population. Ambient benzene represents a potential threat to public health, and further investigations are needed to support timely pollution regulation and health protection. [ABSTRACT FROM AUTHOR]

Background: Circulating omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) have been associated with various chronic diseases and mortality, but results are conflicting. Few studies examined the role of omega-6/omega-3 ratio in mortality. Methods: We investigated plasma omega-3 and omega-6 PUFAs and their ratio in relation to all-cause and cause-specific mortality in a large prospective cohort, the UK Biobank. Of 85,425 participants who had complete information on circulating PUFAs, 6461 died during follow- up, including 2794 from cancer and 1668 from cardiovascular disease (CVD). Associations were estimated by multivariable Cox proportional hazards regression with adjustment for relevant risk factors. Results: Risk for all three mortality outcomes increased as the ratio of omega-6/omega-3 PUFAs increased (all Ptrend <0.05). Comparing the highest to the lowest quintiles, individuals had 26% (95% CI, 15-38%) higher total mortality, 14% (95% CI, 0-31%) higher cancer mortality, and 31% (95% CI, 10-55%) higher CVD mortality. Moreover, omega-3 and omega-6 PUFAs in plasma were all inversely associated with all-cause, cancer, and CVD mortality, with omega-3 showing stronger effects. Conclusions: Using a population-based cohort in UK Biobank, our study revealed a strong association between the ratio of circulating omega-6/omega-3 PUFAs and the risk of all-cause, cancer, and CVD mortality. Funding: Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institute of Health under the award number R35GM143060 (KY). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. [ABSTRACT FROM AUTHOR]

Which life satisfaction components could be a target of positive psychological interventions for longevity is largely unknown. We aimed to investigate association of the composite measure of life satisfaction and its individual components with mortality. This cohort study included UK Biobank participants who responded to questions concerning five components of life satisfaction at baseline. We generated a composite score representing overall life satisfaction, ranging from 0 (lowest) to 5 (highest). The outcomes were all-cause and cause-specific mortality. We used multivariable Cox regression to estimate hazard ratios (HR) for the associations of interest. Among 165,842 eligible participants, 12,261 all-cause deaths were observed over a median of 12.9-year follow-up. Overall life satisfaction was inversely associated with all-cause mortality (adjusted HR 0.94 [95% CI: 0.93–0.95] per 1 score increment). Health satisfaction showed the strongest association with all-cause mortality, with a fully adjusted HR of 0.52 (95% CI: 0.49–0.55) for high/extreme satisfaction and 0.63 (95% CI: 0.59–0.66) for moderate satisfaction, compared with unsatisfaction (P-trend<0.001), independent of other satisfaction components, regardless of physical health and sociodemographics. The association for family, friendship, work and financial satisfaction was attenuated when adjusted for other life satisfaction components. Similar findings were observed for cause-specific mortality. Observational study with single baseline measurement of life satisfaction precludes the ability to establish causal relationship. Higher overall life satisfaction was associated with lower mortality. As the major contributor to lower mortality regardless of physical health and sociodemographics, health satisfaction could be an important target of positive psychological interventions for longevity. • People who felt satisfied with more aspects of life had lower risk of all-cause and cause-specific mortality. • Among the five satisfaction components, health satisfaction was the major contributor to lower risk of mortality. • The inverse association of health satisfaction with mortality did not vary with physical health and sociodemographic status. • Enhancing positive feelings towards health status could serve as a potential strategy for increasing longevity. [ABSTRACT FROM AUTHOR]

We compare the impact of the first two waves of the COVID-19 pandemic on risk of age-standardized mortality by sex, UK country, and English region. Each wave is defined as lasting 26weeks and are consecutive beginning in 2020week 11. The expected rate is estimated from 2015 to 2019 mean and the projected mortality trend from the same period are used to estimate excess mortality. By both measures, excess mortality was highest and lowest in regions of England, London and the South-West, respectively. Excess mortality was consistently higher for males than females. [ABSTRACT FROM AUTHOR]

Background Early-life exposure increases health risks throughout an individual's lifetime. Biological aging is influenced by early-life risks as a key process of disease development, but whether early-life risks could accelerate biological aging and elevate late-life mortality and morbidity risks remains unknown. Knowledge is also limited on the potential moderating role of healthy lifestyle. Methods We investigate associations of three early-life risks around birth, breastfeeding, maternal smoking and birth weight, with biological aging of 202 580 UK Biobank participants (54.9 ± 8.1 years old). Biological aging was quantified as KDM-BA, PhenoAge and frailty. Moderate alcohol intake, no current smoking, healthy diet, BMI <30 kg/m2 and regular physical activity were considered as healthy lifestyles. Mortality and morbidity data were retrieved from health records. Results Individual early-life risk factors were robustly associated with accelerated biological aging. A one-unit increase in the 'early-life risk score' integrating the three factors was associated with 0.060 (SE=0.0019) and 0.036-unit (SE = 0.0027) increase in z-scored KDM-BA acceleration and PhenoAge acceleration, respectively, and with 22.3% higher odds (95% CI: 1.185–1.262) of frailty. Increased chronological age and healthy lifestyles could mitigate the accelerations of KDM-BA and PhenoAge, respectively. Associations of early-life risk score with late-life mortality and morbidity were mediated by biological aging (proportions: 5.66–43.12%). KDM-BA and PhenoAge accelerations could significantly mediate the impact on most outcomes except anxiety, and frailty could not mediate the impact on T2D. Conclusion Biological aging could capture and mediate the late-life health risks stemming from the early-life risks, and could be potentially targeted for healthy longevity promotion. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to describe the natural history and predictors of all‐cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). Methods and results: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS‐LAH)]. One hundred forty‐nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan‐like syndrome, and 3 (2%) NS‐LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36–80) mmHg, P = 0.004]. Over a median follow‐up of 197.5 [inter‐quartile range (IQR) 93.58–370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6–175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69–98.51], 90.42% (95% CI 84.04–94.33), and 84.12% (95% CI 75.42–89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non‐sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all‐cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. Conclusions: These findings highlight a distinct category of patients with Noonan‐like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy‐related HCM. [ABSTRACT FROM AUTHOR]

The concept of biological age has emerged as a measurement that reflects physiological and functional decline with ageing. Here we aimed to develop a deep neural network (DNN) model that predicts biological age from optical coherence tomography (OCT). A total of 84,753 high-quality OCT images from 53,159 individuals in the UK Biobank were included, among which 12,631 3D-OCT images from 8,541 participants without any reported medical conditions at baseline were used to develop an age prediction model. For the remaining 44,618 participants, OCT age gap, the difference between the OCT-predicted age and chronological age, was calculated for each participant. Cox regression models assessed the association between OCT age gap and mortality. The DNN model predicted age with a mean absolute error of 3.27 years and showed a strong correlation of 0.85 with chronological age. After a median follow-up of 11.0 years (IQR 10.9–11.1 years), 2,429 deaths (5.44%) were recorded. For each 5-year increase in OCT age gap, there was an 8% increased mortality risk (hazard ratio [HR] = 1.08, CI:1.02–1.13, P = 0.004). Compared with an OCT age gap within ± 4 years, OCT age gap less than minus 4 years was associated with a 16% decreased mortality risk (HR = 0.84, CI: 0.75–0.94, P = 0.002) and OCT age gap more than 4 years showed an 18% increased risk of death incidence (HR = 1.18, CI: 1.02–1.37, P = 0.026). OCT imaging could serve as an ageing biomarker to predict biological age with high accuracy and the OCT age gap, defined as the difference between the OCT-predicted age and chronological age, can be used as a marker of the risk of mortality. [ABSTRACT FROM AUTHOR]

Frailty, social isolation, and loneliness have individually been associated with adverse health outcomes. This study examines how frailty in combination with loneliness or social isolation is associated with socioeconomic deprivation and with all-cause mortality and hospitalisation rate in a middle-aged and older population. Baseline data from 461,047 UK Biobank participants (aged 37–73) were used to assess frailty (frailty phenotype), social isolation, and loneliness. Weibull models assessed the association between frailty in combination with loneliness or social isolation and all-cause mortality adjusted for age/sex/smoking/alcohol/socioeconomic-status and number of long-term conditions. Negative binomial regression models assessed hospitalisation rate. Frailty prevalence was 3.38%, loneliness 4.75% and social isolation 9.04%. Frailty was present across all ages and increased with age. Loneliness and social isolation were more common in younger participants compared to older. Co-occurrence of frailty and loneliness or social isolation was most common in participants with high socioeconomic deprivation. Frailty was associated with increased mortality and hospitalisation regardless of social isolation/loneliness. Hazard ratios for mortality were 2.47 (2.27–2.69) with social isolation and 2.17 (2.05–2.29) without social isolation, 2.14 (1.92–2.38) with loneliness and 2.16 (2.05–2.27) without loneliness. Loneliness and social isolation were associated with mortality and hospitalisation in robust participants, but this was attenuated in the context of frailty. Frailty and loneliness/social isolation affect individuals across a wide age spectrum and disproportionately co-occur in areas of high deprivation. All were associated with adverse outcomes, but the association between loneliness and social isolation and adverse outcomes was attenuated in the context of frailty. Future interventions should target people living with frailty or loneliness/social isolation, regardless of age. [ABSTRACT FROM AUTHOR]

The aim of this analysis was to explore mortality outcomes for kidney transplant candidates receiving older living donor kidneys (age ≥60 years) versus younger deceased donors or remaining on dialysis. From 2000 to 2019, all patients on dialysis listed for their first kidneyalone transplant were included in a retrospective cohort analysis of UK transplant registry data. The primary outcome was all-cause mortality, with survival analysis conducted by intention-to-treat principle. Time-to-death from listing was modelled using nonproportional hazard Cox regression models with transplantation handled as a time-dependent covariate. A total of 32,978 waitlisted kidney failure patients formed the primary study cohort, of whom 18,796 (58.5%) received a kidney transplant (1,557 older living donor kidneys and 18,062 standard criteria donor kidneys). Older living donor kidney transplantation constituted only 17.0% of all living donor kidney transplant activity (overall cohort; n = 9,140). Recipients of older living donor kidneys had reduced allcause mortality compared to receiving SCD kidneys (HR 0.904, 95% CI 0.845–0.967, p = 0.003) and much lower all-cause mortality versus remaining on the waiting list (HR 0.160, 95% CI 0.149–0.172, p < 0.001). Older living kidney donors should be actively explored to expand the living donor kidney pool and are an excellent treatment option for waitlisted kidney transplant candidates. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes (T2D) is associated with an increased risk of premature death. Whether multifactorial risk factor modification could attenuate T2D-related excess risk of death is unclear. We aimed to examine the association of risk factor target achievement with mortality and life expectancy among patients with T2D, compared with individuals without diabetes. Methods: In this longitudinal cohort study, we included 316 995 participants (14 162 with T2D and 302 833 without T2D) free from cardiovascular disease (CVD) or cancer at baseline between 2006 and 2010 from the UK Biobank. Participants with T2D were categorised according to the number of risk factors within target range (non-smoking, being physically active, healthy diet, guideline-recommended levels of glycated haemoglobin, body mass index, blood pressure, and total cholesterol). Survival models were applied to calculate hazard ratios (HRs) for mortality and predict life expectancy differences. Results: Over a median follow-up of 13.8 (IQR 13.1–14.4) years, deaths occurred among 2105 (14.9%) participants with T2D and 18 505 (6.1%) participants without T2D. Compared with participants without T2D (death rate per 1000 person-years 4.51 [95% CI 4.44 to 4.57]), the risk of all-cause mortality among those with T2D decreased stepwise with an increasing number of risk factors within target range (0–1 risk factor target achieved: absolute rate difference per 1000 person-years 7.34 [4.91 to 9.78], HR 2.70 [2.25 to 3.25]; 6–7 risk factors target achieved: absolute rate difference per 1000 person-years 0.68 [-0.62 to 1.99], HR 1.16 [0.93 to 1.43]). A similar pattern was observed for CVD and cancer mortality. The association between risk factors target achievement and all-cause mortality was more prominent among participants younger than 60 years than those 60 years or older (P for interaction = 0.012). At age 50 years, participants with T2D who had 0–1 and 6–7 risk factors within target range had an average 7.67 (95% CI 6.15 to 9.19) and 0.99 (-0.59 to 2.56) reduced years of life expectancy, respectively, compared with those without T2D. Conclusions: Individuals with T2D who achieved multiple risk factor targets had no significant excess mortality risk or reduction in life expectancy than those without diabetes. Early interventions aiming to promote risk factor modification could translate into improved long-term survival for patients with T2D. [ABSTRACT FROM AUTHOR]

Background: Diabetes patients are at higher risk for mortality than the general population; however, little is known about whether the excess mortality risk associated with diabetes could be mitigated or nullified via controlling for risk factors. Methods: We included 18,535 diabetes patients and 91,745 matched individuals without diabetes without baseline cancer or cardiovascular disease (CVD), followed up from 2006 to 2021. The main exposure was the number of optimized risk factors including glycated hemoglobin < 53 mmol/mole, systolic blood pressure < 140 mmHg and diastolic blood pressure < 90 mmHg, no albuminuria, non-current smoking and low-density lipoprotein cholesterol (LDL-C) < 2.5 mmol/L. We used Cox proportional hazards models to explore the association of the degree of risk factor control with all-cause mortality, cancer mortality, CVD mortality and other mortality. Results: Each additional risk factor control was associated with a 16, 10, 21 and 15% lower risk of all-cause mortality, cancer mortality, CVD mortality and other mortality, respectively. Optimal risk factors control (controlling 5 risk factors) was associated with a 50% (HR 0.50, 95% CI 0.41–0.62), 74% (HR 0.26, 95% CI 0.16–0.43) and 38% (HR 0.62, 95% CI 0.44–0.87) lower risk of all-cause mortality, CVD mortality and other mortality, respectively. Diabetes patients with 4, 3 and 5 or more controlled risk factors, respectively, showed no excess risk of all-cause mortality, cancer mortality and CVD mortality compared to matched non-diabetes patients. Conclusions: The results from this study indicate that optimal risk factor control may eliminate diabetes-related excess risk of all-cause mortality, CVD mortality and other mortality. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of oral lichen planus (OLP) on the long‐term prognosis of oral epithelial dysplasia (OED). Methods: Retrospective single‐centre cohort study using the 2007–2019 database of the Head and Neck Cancer and Oral Medicine units of University College London Hospital. The exposure of interest was the presence of OLP, and the prognostic outcomes included the development of new primary episodes of OED, progression to malignancy and mortality. Cox proportional hazard and Poisson regression models were performed. Results: A total of 299 patients, of whom 144 had OED arising on the background of OLP (OLP/OED) and 155 had OED without underlying OLP (non‐OLP/OED), were included. A pre‐existing diagnosis of OLP was significantly associated with a twofold increased risk of subsequent primary OED events (HR = 2.02, p = 0.04), which also developed faster (1.46 vs. 2.96 years, p = 0.04) and with more involvement of non‐cancer‐prone sites (p = 0.001) than in the non‐OLP/OED group. There was no difference between groups in the progression to malignancy or mortality. Conclusions: Oral lichen planus/OED patients are at higher risk of multiple episodes of primary OED, which can develop faster and at non‐cancer‐prone sites as compared to non‐OLP/OED individuals. Further research is needed to clarify the effects of OLP upon progression to OSCC and mortality. [ABSTRACT FROM AUTHOR]

Objective To analyze the relationship between the proportion of omega-6/omega-3 and mortality in patients with cardiovascular disease (CVD), so as to provide reference for reducing the risk of death in patients with CVD. Methods The data of were collected from the UK perspective cohort (UK Biobank) database. The exposure variable was the proportion of plasma omega6/omega-3, and the outcomes were all- cause deaths, CVD deaths, ischemic heart disease (IHD) deaths, and stroke deaths. Multivariate Cox proportional hazard regression model was used to analyze the relationship between omega-6/ omega-3 ratio and death risk of CVD patients. Risk ratio hazard ratio (HR) and 95% confidence interval (CI) were calculated. Gender, age, and other risk factors were stratified and their interaction with omega-6/omega-3 ratio was analyzed. Restricted cubic spline (RCS) was used to describe the dose-response relationship. Sensitivity analysis was used to test the robustness of the model. Results A total of 35 096 participants were enrolled. Multivariate Cox proportional hazard regression model showed that all-cause deaths, CVD deaths, and ischemic heart disease deaths risk increased in CVD patients with the in¬crease of the proportion of omega-6/omega-3. For each unit increase in omega-6/omega-3 ratio, the risk of all-cause, CVD, and IHD deaths increased by 2.1% (HR=1.021, 95%CI: 1.016-0.025), 1.9% (HR=1.019, 95%CI: 1.010-1.028), and 2.3% (HR =1.023, 95% CI: 1.013-1.034), respectively. The proportion of omega-6/omega-3 was grouped according to quartile method and included in the model as a classified variable. Compared with Q1, the HR of all-cause, CVD, and IHD deaths of Q4 was 1.394 (95% CI: 1.267-1.534), 1.292 (95%CI: 1.085-1.540), and 1.528 (95% CI: 1.200-1.945), respectively, and no correlation was found between Q4 and stroke death risk (HR=0.987, 95%CI: 0.660-1.477). The results of RCS showed that the proportion of omega-6/omega3 was positively correlated with the risk of death. Conclusion The proportion of omega-6/ omega-3 is a risk factor for death in patients with CVD. [ABSTRACT FROM AUTHOR]

Background During the pandemic, countries utilized various forms of statistical estimations of coronavirus disease-2019 (COVID-19) impact. Differences between databases make direct comparisons and interpretations of data in different countries a challenge. We evaluated country-specific approaches to COVID-19 data and recommended changes that would improve future international collaborations. Methods We compared the COVID-19 reports presented on official UK (National Health System), Israeli (Department of Health), Latvian (Center for Disease Prevention and Control) and USA (Centers for Disease Control and Prevention) health authorities' websites. Results Our analysis demonstrated critical differences in the ways COVID-19 statistics were made available to the general and scientific communities. Specifically, the differences in approaches were found in the presentation of the number of infected cases and tests, and percentage of positive cases, the number of severe cases, the number of vaccinated, and the number and percent of deaths. Conclusion Findability, Accessibility, Interoperability and Reusability principles could guide the development of essential global standards that provide a basis for communication within and outside of the scientific community. [ABSTRACT FROM AUTHOR]

Background: Current recommendations advocate the achievement of an optimal glucose control (HbA1c < 69 mmol/mol) prior to elective surgery to reduce risks of peri- and post-operative complications, but the relevance for this glycaemic threshold prior to Bariatric Metabolic Surgery (BMS) following a specialist weight management programme remains unclear. Methods: We undertook a retrospective cohort study of patients with type 2 diabetes mellitus (T2DM) who underwent BMS over a 6-year period (2016–2022) at a regional tertiary referral following completion of a specialist multidisciplinary weight management. Post-operative outcomes of interest included 30-day mortality, readmission rates, need for Intensive Care Unit (ICU) care and hospital length of stay (LOS) and were assessed according to HbA1c cut-off values of < 69 (N = 202) and > 69 mmol/mol (N = 67) as well as a continuous variable. Results: A total of 269 patients with T2D were included in this study. Patients underwent primary Roux en-Y gastric bypass (RYGB, n = 136), Sleeve Gastrectomy (SG, n = 124), insertion of gastric band (n = 4) or one-anastomosis gastric bypass (OAGB, n = 4). No significant differences in the rates of complications were observed between the two groups of pre-operative HbA1c cut-off values. No HbA1c threshold was observed for glycaemic control that would affect the peri- and post-operative complications following BMS. Conclusions: We observed no associations between pre-operative HbA1C values and the risk of peri- and post-operative complications. In the context of a specialist multidisciplinary weight management programme, optimising pre-operative HbA1C to a recommended target value prior to BMS may not translate into reduced risks of peri- and post-operative complications. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported the association between dietary inflammatory index (DII) and the SARS-CoV-2 infection risk, severity or mortality of COVID-19, however, the outcomes remain controversial. Objective: We sought to examine whether a dose-response association of DII and SARS-CoV-2 infection exists. Design: A dose-response meta-analysis was performed to investigate the association of DII and SARS-CoV-2 infection. We conducted a systematic search of PubMed, Embase and Web of Science up to March 15th, 2023. The odds ratios (OR) of DII and COVID-19 risk and severity were computed. Results: Totally, 5 studies were included (1 from UK and 4 from Iran), consisting of 197,929 participants with 12,081 COVID-19 cases. Although there was heterogeneity among studies, the results indicated that higher DII was independently related to higher SARS-CoV-2 infection incidence (OR = 1.57, 95% CI: 1.14, 2.17) and COVID-19 severity (OR = 1.11, 95% CI: 1.07, 1.15) but not COVID-19 mortality (risk ratio = 1.13, 95% CI: 1.00, 1.27). The incidence of SARS-CoV-2 infection increased by 31% for each 1-point increase in the E-DII (OR = 1.31, 95% CI: 1.20, 1.43). Conclusions: This meta-analysis suggests that an elevated DII score is associated with increased SARS-CoV-2 infectious risk and severity of COVID-19. There were not enough studies on COVID-19 mortality. Further large prospective studies in different countries are warranted to validate our results. [ABSTRACT FROM AUTHOR]

Depression is a global health issue, associated with increased risk of cardiovascular disease (CVD) and premature death, but whether the association varied across different socioeconomic status (SES), and mechanisms responsible for this association is unclear. We aimed to evaluate the association of depressive symptoms with the risk of incident CVD and mortality in people of low, medium, and high SES, and determine the extent to which lifestyle behaviors could explain the association. This study included 314,800 participants from the UK Biobank. Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2). Information on socioeconomic status and lifestyle was obtained from baseline assessment. During 12 years of follow-up, 29,074 incident CVD cases and 16,673 deaths were documented. The increased CVD risk in participants with depressive symptoms (versus without) was more pronounced as SES decreased, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 1.30 (1.22, 1.39), 1.27 (1.17, 1.37), and 1.17 (0.97, 1.41) in participants of low, medium, and high SES, respectively. The corresponding HRs (95% CIs) for all-cause mortality were 1.16 (1.07, 1.26), 1.21 (1.08, 1.36), and 1.24 (0.95, 1.61). In addition, multiple lifestyle factors together explained 14.4% to 32.8% of the elevated CVD and mortality risk due to depressive symptoms. Moderate sensitivity of PHQ-2, lacked information on the severity of depression, baseline measurement of lifestyle. Depressive symptoms were associated with higher risks of incident CVD and mortality, especially in low SES groups, and lifestyle behaviors only explained a moderate proportion of the association. These findings indicated that health policies targeting healthy lifestyle promotion alone might not be sufficient, and other measures tackling social inequity are warranted to attenuate the elevated health risk due to depression. • Depressive symptoms were associated with higher risk of CVD and mortality especially in low socioeconomic status group. • Multiple lifestyle factors explained a moderate proportion of the elevated risk of CVD and mortality due to depression. • Tackling socioeconomic inequity is of great importance in the prevention of CVD and premature death due to depression. [ABSTRACT FROM AUTHOR]

Backgrounds: To compare factor(s) contributing to aetiology, management and clinical outcome(s) of paediatric patients acquiring acute pancreatitis (AP) at two major university paediatric surgical centres in Liverpool and Bangkok. Methods: All patients (<18 years) with an index diagnosis of AP (ICD 10 coding) during 2006–2016 were studied. Results: 121 patients included n = 79 (65.3%) in Thailand versus n = 42 (34.7%) in the UK centre with no difference(s) in age at diagnosis at 10.4 ± 4.5 and 11.7 ± 6 years. (P = 0.12). Major AP aetiology(s) in Thailand were medications (39.2%) and choledochal cysts (8.9%). In the UK—gallstone disease (21.4%), and medications (16.7%) were leading factors (P < 0.01). Ultrasonography was deployed more frequently in the UK versus Thai centre (74.3% vs. 49.1%; P < 0.01). Pancreatitis was confirmed by imaging in 67.9% (Thai) and 62.9% (UK) patients (P = 0.47). Most patients at both centres had a mild‐grade pancreatitis illness (95% Thai vs. 90.5% UK; P = 0.28) while 12.7% of Thai and 19% of UK children developed pancreatitis‐related complication (P = 0.37). Overall mortality rate (%) was significantly higher in the Thai versus UK centre (27.8% vs. 9.5%; P = 0.02). Conclusions: Aetiology of acute pancreatitis appears to vary between UK and Thailand children. Timely early diagnosis and healthcare pathways may be driven by local patient‐related factor(s). The higher mortality (%) observed in Thailand versus UK in this comparative study was linked to underlying co‐existent chronic medical condition(s) in vulnerable patient cohorts. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES This nationwide retrospective cohort study assessed the impact of the explanted valve type on reoperative outcomes in aortic valve surgery within the UK over a 23-year period. METHODS Data were sourced from the National Institute for Cardiovascular Outcomes Research (NICOR) database. All patients undergoing first-time isolated reoperative aortic valve replacement between 1996 and 2019 in the UK were included. Concomitant procedures, homograft implantation or aortic root enlargement were excluded. Propensity score matching was utilized to compare outcomes and risk factors for in-hospital mortality was evaluated through multivariable logistic regression. Final model selection was conducted using Akaike Information Criterion through bootstrapping. The primary end point was in-hospital mortality, and secondary end points included postoperative morbidities. RESULTS Out of 2371 patients, 24.9% had mechanical and 75% had bioprosthetic valves implanted during the primary procedure. Propensity matched groups of 324 patients each, were compared. In-hospital mortality for mechanical and bioprosthetic valve explants was 7.1% and 5.9%, respectively (P  = 0.632). On multivariable logistic regression analysis, valve type was not a risk factor for mortality [odds ratio (OR) 0.62, 95% confidence interval (CI) 0.37–1.05; P  = 0.1]. Age (OR 1.03, 95% CI 1.01–1.05; P  < 0.05), left ventricular ejection fraction (OR 1.62, 95% CI 1.08–2.42; P  < 0.05), creatinine ≥ 200 mg/dl (OR 2.21, 95% CI 1.17–4.04; P  < 0.05) and endocarditis (OR 2.66, 95% CI 1.71–4.14; P  < 0.05) emerged as risk factors for mortality. CONCLUSIONS The type of valve initially implanted (mechanical or bioprosthetic) did not determine mortality. Instead, age, left ventricular ejection fraction, renal impairment and endocarditis were significant risk factors for in-hospital mortality. [ABSTRACT FROM AUTHOR]

Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n  = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of −50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes. [ABSTRACT FROM AUTHOR]

The healthy aging index (HAI) has been recently developed as a surrogate measure of biological age. However, to what extent the HAI is associated with all-cause and cause-specific mortality and whether this association differs in younger and older adults remains unknown. We aimed to quantify the association between the HAI and mortality in a population of UK adults. In the prospective cohort study, data are obtained from the UK Biobank. Five HAI components (systolic blood pressure, reaction time, cystatin C, serum glucose, forced vital capacity) were scored 0 (healthiest), 1, and 2 (unhealthiest) according to sex-specific tertiles or clinically relevant cut-points and summed to construct the HAI (range 0–10). Cox proportional hazard regression models were used to estimate the associations of the HAI with the risk of all-cause and cause-specific mortality. 387,794 middle-aged and older participants were followed up for a median of 8.9 years (IQR 8.3–9.5). A total of 14,112 all-cause deaths were documented. After adjustments, each 1-point increase in the HAI was related to a higher risk of all-cause mortality (hazards ratio [HR], 1.17; 95%CI, 1.15–1.18). Such association was stronger among adults younger than 60 years (1.19, 1.17–1.21) than that among those 60 years and older (1.15, 1.14–1.17) (P interaction < 0.001). For each unit increment of the HAI, the multivariate-adjusted HRs for risk of death were 1.28 (1.25–1.31) for cardiovascular diseases, 1.09 (1.07–1.10) for cancer, 1.36 (1.29–1.44) for digestive disease, 1.42 (1.35–1.48) for respiratory disease, 1.42 (1.33–1.51) for infectious diseases, and 1.15 (1.09–1.21) for neurodegenerative disease, respectively. Our findings indicate that the HAI is positively associated with all-cause and cause-specific mortality independent of chronological age. Our results further underscore the importance of effective early-life interventions to slow aging and prevent premature death. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is known as one of the important risk factors for the severity and mortality of COVID-19. Here, we evaluate the impact of T2D and its genetic susceptibility on the severity and mortality of COVID-19, using 459,119 individuals in UK Biobank. Utilizing the polygenic risk scores (PRS) for T2D, we identified a significant association between T2D or T2D PRS, and COVID-19 severity. We further discovered the efficacy of vaccination and the pivotal role of T2D-related genetics in the pathogenesis of severe COVID-19. Moreover, we found that individuals with T2D or those in the high T2D PRS group had a significantly increased mortality rate. We also observed that the mortality rate for SARS-CoV-2-infected patients was approximately 2 to 7 times higher than for those not infected, depending on the time of infection. These findings emphasize the potential of T2D PRS in estimating the severity and mortality of COVID-19. Study of 459,119 UK Biobank participants reveals that type 2 diabetes (T2D) and a high genetic susceptibility to T2D significantly increase the severity and mortality rate in COVID-19 cases. [ABSTRACT FROM AUTHOR]