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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]

The relationship between high plasma high-density lipoprotein cholesterol (HDL-C) and cause and mortality are not well established in healthy older people. This study examined the associations between HDL-C levels and mortality in initially healthy older men and women. This analysis included participants from the Aspirin in Reducing Events in the Elderly (ASPREE; n=18,668) trial and a matched cohort from the UK Biobank (UKB; n=62,849 ≥65 years). Cox regression was used to examine hazard ratios between HDL-C categories <1.03 mmol/L, 1.03–1.55 mmol/L (referent category), 1.55–2.07 mmol/L, and >2.07 mmol/L and all-cause, cancer, cardiovascular disease (CVD), and "non-cancer non-CVD" mortality. Genetic contributions were assessed using a polygenic score for HDL-C. Among ASPREE participants (aged 75±5 years), 1836 deaths occurred over a mean follow-up of 6.3±1.8 years. In men, the highest category of HDL-C levels was associated with increased risk of all-cause (HR 1.60, 95% CI 1.26–2.03), cancer (HR 1.37, 95% CI 0.96–2.00), and "non-cancer non-CVD" mortality (HR 2.35, 95% CI 1.41–3.42) but not CVD mortality (HR 1.08, 95% CI 0.60–1.94). The associations were replicated among UKB participants (aged 66.9±1.5 years), including 8739 deaths over a mean follow-up of 12.7±0.8 years. There was a non-linear association between HDL-C levels and all-cause and cause-specific mortality. The association between HDL-C levels and mortality was unrelated to variations in the HDL-C polygenic score. No significant association was found between HDL-C levels and mortality in women. Higher HDL-C levels are associated with increased risk from cancer and "non-cancer non-CVD" mortality in healthy older men but no such relationship was observed in women. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) has a rising global prevalence. However, the understanding of its impact on mortality remains inconsistent so we explored the association between IBD and all-cause and cause-specific mortality. This study included 502,369 participants from the UK Biobank, a large, population-based, prospective cohort study with mortality data through 2022. IBD was defined by baseline self-report or from primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality in multivariable Cox proportional hazards regression models. A total of 5799 (1.2%) participants had a history of IBD at baseline. After a median follow-up of 13.7 years, 44,499 deaths occurred. Having IBD was associated with an increased risk of death from all causes (HR = 1.16, 95% CI = 1.07–1.24) and cancer (HR = 1.16, 95% CI = 1.05–1.30), particularly colorectal cancer (CRC) (HR = 1.56, 95% CI = 1.17–2.09). We observed elevated breast cancer mortality rates for individuals with Crohn's disease, and increased CRC mortality rates for individuals with ulcerative colitis. In stratified analyses of IBD and all-cause mortality, mortality risk differed by individuals' duration of IBD, age at IBD diagnosis, body mass index (BMI) (P Heterogeneity = 0.03) and smoking status (P Heterogeneity = 0.01). Positive associations between IBD and all-cause mortality were detected in individuals diagnosed with IBD for 10 years or longer, those diagnosed before the age of 50, all BMI subgroups except obese individuals, and in never or current, but not former smokers. We found that having IBD was associated with increased risks of mortality from all causes, all cancers, and CRC. This underscores the importance of enhanced patient management strategies and targeted prevention efforts in individuals with IBD. [ABSTRACT FROM AUTHOR]

Background: Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37--73 years. Methods: Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41--50, 51--60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses. Results: Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41--50, 51--60, and >60 years, especially at 51--60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51--60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088--2.416, HR for mortality: 1.276--3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51--60 years. Conclusion: Our findings highlighted that the age at diagnosis of diabetes, especially 51--60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer. [ABSTRACT FROM AUTHOR]

It is unknown whether the well-known association between vitamin D deficiency and mortality could be explained by the immune system modulating effects of vitamin D, which may protect from a systemic inflammatory response (SIR) to adverse health conditions. This study aims to investigate the interrelationships of vitamin D deficiency, biomarkers of SIR, and mortality. We used multivariate logistic regression with adjustment for 51 covariates to assess the associations of vitamin D deficiency with disadvantageous levels of nine biomarkers of SIR in the UK Biobank cohort. Furthermore, we tested with Cox regression and mediation analysis whether biomarkers of SIR and vitamin D deficiency were independently associated with mortality. We included 397,737 participants aged 37–73 years. Vitamin D deficiency was associated with disadvantageous levels of all blood cell count-based biomarkers, but not with C-reactive protein (CRP)-based biomarkers after adjustment for body weight. Vitamin D deficiency and all biomarkers of SIR were significantly associated with all-cause mortality and mortality from cancer, cardiovascular and respiratory disease. The strength of these associations was unaltered if vitamin D deficiency and biomarkers of SIR were put in the same model. This finding was further supported by the mediation analyses. This study showed that vitamin D deficiency is associated with disadvantageous levels of blood cell count-based but not CRP-based biomarkers of SIR. Vitamin D deficiency and systemic inflammation were independently and strongly associated with mortality. The potential of clinical interventions against both vitamin D deficiency and underlying causes of systemic inflammation should be explored. [ABSTRACT FROM AUTHOR]

Background: The American Heart Association recently introduced a novel cardiovascular health (CVH) metric, Life's Essential 8 (LE8), for health promotion. However, the relationship between LE8 and cancer mortality risk remains uncertain., Methods: We investigated 17,076 participants from US National Health and Nutrition Examination Survey (US NHANES) and 272,727 participants from UK Biobank, all free of cancer at baseline. The CVH score, based on LE8 metrics, incorporates four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (body mass index, lipid, blood glucose, and blood pressure). Self-reported questionnaires assessed health behaviors. Primary outcomes were mortality rates for total cancer and its subtypes. The association between CVH score (continuous and categorical variable) and outcomes was examined using Cox model with adjustments. Cancer subtypes-related polygenic risk score (PRS) was constructed to evaluate its interactions with CVH on cancer death risk., Results: Over 141,526 person-years in US NHANES, 424 cancer-related deaths occurred, and in UK Biobank, 8,872 cancer deaths were documented during 3,690,893 person-years. High CVH was associated with reduced overall cancer mortality compared to low CVH (HR 0.58, 95% CI 0.37-0.91 in US NHANES; 0.51, 0.46-0.57 in UK Biobank). Each one-standard deviation increase in CVH score was linked to a 19% decrease in cancer mortality (HR: 0.81; 95% CI: 0.73-0.91) in US NHANES and a 19% decrease (HR: 0.81; 95% CI: 0.79-0.83) in UK Biobank. Adhering to ideal CVH was linearly associated with decreased risks of death from lung, bladder, liver, kidney, esophageal, breast, colorectal, pancreatic, and gastric cancers in UK Biobank. Furthermore, integrating genetic data revealed individuals with low PRS and high CVH exhibited the lowest mortality from eight cancers (HRs ranged from 0.36 to 0.57) compared to those with high PRS and low CVH. No significant modification of the association between CVH and mortality risk for eight cancers by genetic predisposition was observed. Subgroup analyses showed a more pronounced protective association for overall cancer mortality among younger participants and those with lower socio-economic status., Conclusions: Maintaining optimal CVH is associated with a substantial reduction in the risk of overall cancer mortality. Adherence to ideal CVH correlates linearly with decreased mortality risk across multiple cancer subtypes. Individuals with both ideal CVH and high genetic predisposition demonstrated significant health benefits. These findings support adopting ideal CVH as an intervention strategy to mitigate cancer mortality risk and promote healthy aging., (© 2024. The Author(s).)

Background and aims: Various smoking behaviors, including smoking initiation, age of initiation, heaviness of smoking and smoking cessation, have been individually related to the risk of mortality; however, no study has assessed these smoking behaviors jointly in relation to mortality. Our study aimed to measure prospectively the association of panoramic smoking burden (PSB), generated from the four aforementioned smoking behaviors, with all‐cause and cause‐specific mortality, and measure whether such associations are modified by genetic variations. Design Prospective cohort study. Setting: UK Biobank. Participants: A total of 360 937 participants aged between 37 and 73 years were enrolled in 2006–10 and ‐followed‐up to 2018. Measurements The exposure was PSB, constructed based on four smoking behaviors including smoking initiation, age of initiation, heaviness of smoking and smoking cessation in a weighted method. A genetically determined PSB was also constructed with smoking‐associated single nucleotide polymorphisms (SNPs) and categorized into tertiles. The primary outcomes were all‐cause and cause‐specific mortality. Findings We identified 15 968 deaths [9022 from cancer and 5092 from cardiovascular disease (CVD)] over a median of 11.36 years' follow‐up. For all‐cause mortality, compared with participants with the PSB of zero, the hazard ratios of participants who had a PSB of one, two, three and four were 1.23 [95% confidence intervals (CI) = 1.18–1.29), 1.66 (95% CI = 1.59–1.75), 3.33 (95% CI = 3.17–3.51) and 5.76 (95% CI = 4.66–7.13), respectively. Among participants within each genetic risk category, low and intermediate PSB were associated with 45–58% reduced risk of all‐cause death compared with high PSB. Analysis of population‐attributable risk percentage indicated that 21.9, 19.1 and 24.7% of all‐cause‐, cancer‐ and CVD‐specific death could have been avoided if all ever smokers initiated smoking after age 18 years, smoked < 20 cigarettes/day and quit smoking. Conclusions: The panoramic smoking burden, based on smoking initiation, age of initiation, heaviness of smoking and smoking cessation, appears to be associated with all‐cause and cause‐specific mortality in a gradient manner with increasing panoramic smoking burden independent of other traditional and genetic risk factors. [ABSTRACT FROM AUTHOR]

Objectives: Dietary patterns, characterised by protein, polyunsaturated fatty acids, and vitamin D, reduce the odds of malnutrition in cancer survivors. However, it is unclear whether these dietary patterns also improve prognosis. This study prospectively examined associations between dietary patterns linked to lower odds of malnutrition and the risk of all-cause and cancer mortality in adult cancer survivors from the UK Biobank cohort., Design: Prospective observational study., Setting and Participants: Cancer survivors from the UK Biobank (mean ± SD, 7.1 ± 6.3 years since diagnosis) were included (n = 2415; 59.7 ± 7.1 years; 60.7% female)., Measurements: Dietary intake was estimated using the Oxford WebQ 24-h dietary assessment. Dietary patterns ('high oily fish and nuts', and 'low oily fish') were derived using reduced rank regression (response variables: protein (g/kg/day), polyunsaturated fatty acids (g/day) and vitamin D (μg/day)). Cox proportional hazard models estimated hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cancer mortality. Nonlinear relationships were examined using restricted cubic splines. Models were adjusted for demographic and health characteristics. Sub-group analyses investigated relationships in sub-samples of adults with i) high nutritional risk (lung, gastrointestinal, haematological, or head and neck tumours) and ii) recent cancer diagnosis (cancer diagnosis within two years prior to assessment)., Results: Deaths due to all-causes (n = 305) and cancer (n = 249) were identified during a median 10.4 (IQR: 10.2-10.8) years follow-up. There were no statistically significant linear associations between the dietary patterns and all-cause or cancer mortality. However, a U-shaped association between the 'high oily fish and nuts' pattern, characterised by higher intake of oily fish and nuts and seeds, and all-cause mortality (p-non-linearity = 0.004) was identified, as well as with all-cause (p-non-linearity = 0.006) and cancer mortality (p-non-linearity = 0.035) in adults with a high nutritional risk cancer diagnosis (lung, gastrointestinal, haematological, or head and neck tumours), indicating that both above and below mean intake was associated with increased risk. The 'low oily fish' pattern, characterised by lower oily fish but higher potato intake, also had a non-linear association with all-cause mortality (p-non-linearity = 0.046) where lower but not higher than mean intake increased mortality risk. No dietary patterns were significantly associated with mortality in adults with a recent cancer diagnosis., Conclusion: 'High oily fish and nuts' or 'low oily fish' dietary patterns that were protective against malnutrition were associated with risk of all-cause and cancer mortality in adults with cancer. Future research should assess the efficacy of these dietary patterns in the acute treatment period when malnutrition is most prevalent., (Copyright © 2023. Published by Elsevier Masson SAS.)

The potential of physical activity (PA) to attenuate the effects of alcohol consumption on the risks of alcohol‐related cancer mortality is unknown. We used data from participants aged 30 years and over in 10 British population‐based surveys (Health Surveys for England 1994, 1997, 1998, 1999, 2003, 2004, 2006 and 2008 and the Scottish Health Surveys 1998 and 2003). Alcohol‐related cancer mortality included oral cavity, throat, larynx, oesophagus, liver, colorectal, stomach and female breast (conservative definition), and additionally pancreas and lung (broad definition). Alcohol consumption was categorised into six groups based on the UK units/week: (a) never‐drinkers, (b) ex‐drinkers, (c) occasional drinkers, (d) within guidelines (<14 UK units/week [women]; <21 UK units/week [men]), (e) hazardous (14‐35 [women]; 21‐49 [men]) and (f) harmful (>35 [women]; >49 [men]). PA was categorised using two dichotomous classifications based on the lower (7.5 Metabolic Equivalent Task [MET]‐hours/week) and upper (15 MET‐hours/week) recommended limits. Using Cox proportional hazard models, we found a strong direct association between alcohol consumption and mortality risk of alcohol‐related cancers, with a significantly higher risk among ex‐drinkers (Hazard ratio [HR] = 1.46, 95% confidence interval [CI] = [1.09, 1.94]), drinkers who consumed hazardous (HR = 1.39, 95% CI = [1.06, 1.83]) and harmful amounts of alcohol (HR = 1.62, 95% CI = [1.13, 2.30]) compared to never‐drinkers in the fully adjusted model. The increased mortality risks were substantially attenuated when participants in these drinking groups exercised >7.5 MET‐hours/week. PA could be promoted as an adjunct risk minimisation measure for alcohol‐related cancer prevention. What's new? While alcohol consumption contributes to cancer mortality and is pervasive worldwide, many people who drink also engage in physical activity, which has numerous health benefits. The combined impact of these behaviors on cancer mortality risk is unknown. Here, alcohol consumption was strongly associated with alcohol‐related cancer mortality risk among participants from 10 British population‐based studies. This risk, however, was significantly reduced in physically active participants who met at least the lower recommended limit of activity per week. The findings suggest that adopting physical activity as a healthy lifestyle behavior could lessen the impact of alcohol consumption on cancer mortality. [ABSTRACT FROM AUTHOR]

Excessive Ca intakes have been proposed to associate with vascular calcification and a higher risk of prostate cancer. We investigated the associations of supplemental and dietary Ca intake with mortality using data from 497 828 UK Biobank participants. The average follow-up was 4·2 years and 14 255 participants died, 8297 from cancer, 2959 from CVD and 572 from respiratory disease. The use of Ca supplements and milk consumption were associated with differences in mortality in younger (≤65 years) but not in older participants (>65 years, P interaction ≤ 0·04 for all comparisons). Among participants <65 years, there was an inverse association between Ca supplementation (OR 0·91, 95 % CI 0·83, 0·99) and milk consumption (OR 0·93, 95 % CI 0·86, 1·00) with respect to all-cause mortality. In the same age group, milk drinkers had lower odds of cancer mortality (OR 0·89, 95 % CI 0·80, 0·98) but Ca supplement use was associated with increased odds of respiratory mortality (OR 1·69, 95 % CI 1·16, 2·74). All associations in participants aged ≥65 years were null after full adjustment. In sensitivity analyses stratified by hormone replacement therapy, Ca supplement use was associated with decreased odds of cancer mortality in users but increased risk in other women (OR 0·81, 95 % CI 0·69, 0·94 v. OR 1·17, 95 % CI 1·01, 1·35, respectively). To conclude, we saw little evidence for harm with dietary or supplemental Ca. Further studies are required to confirm the proposed interaction with hormone replacement therapy and to exclude reverse causation as a determinant in the association between Ca supplements and increased risk of respiratory diseases. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have suggested that coffee intake may be associated with a reduction in cancer risk. Mendelian randomization (MR) studies can help clarify whether the observed associations are likely to be causal. Here we evaluated whether coffee intake is associated with: (i) overall risk of being diagnosed with/dying from any cancer; and (ii) risk of individual cancers.Methods: We identified 46 155 cases (of which 6998 were fatal) and 270 342 controls of White British ancestry from the UK Biobank cohort (UKB), based on ICD10 diagnoses. Individuals with benign tumours were excluded. Coffee intake was self-reported and recorded based on cup/day consumption. We conducted both observational and summary data MR analyses.Results: There was no observational association between coffee intake and overall cancer risk [odds ratio (OR) per one cup/day increase = 0.99, 95% confidence interval (CI) 0.98, 1.00] or cancer death (OR = 1.01, 0.99, 1.03); the estimated OR from MR is 1.01 (0.94, 1.08) for overall cancer risk and 1.11 (0.95, 1.31) for cancer death. The relationship between coffee intake and individual cancer risks were consistent with a null effect, with most cancers showing little or no associations with coffee. Meta-analysis of our MR findings with publicly available summary data on various cancers do not support a strong causal relationship between coffee and risk of breast, ovarian, lung or prostate cancer, upon correction for multiple testing.Conclusions: Taken together, coffee intake is not associated with overall risk of being diagnosed with or dying from cancer in UKB. For individual cancers, our findings were not statistically inconsistent with earlier observational studies, although for these we were unable to rule out a small effect on specific types of cancer. [ABSTRACT FROM AUTHOR]

Evidence regarding the role of physical frailty in cancer-related outcomes is limited. We aimed to examine the association of frailty with cancer incidence and mortality risk. This prospective study included 348,144 participants free of cancer at baseline from the UK Biobank. Frailty phenotypes (non-frail, pre-frail, and frail) were constructed from 5 components: weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The outcome was incidence and mortality of overall and cite-specific cancers. Cox proportional hazard regression was used to estimate the association of frailty phenotypes with cancer incidence and mortality risk. A total of 43,304 incident cancer cases and 10,152 cancer deaths were documented during a median of 12.0 years of follow-up. For overall cancer, compared with non-frailty, the incidence risk increased by 4% for pre-frailty and 11% for frailty, and the mortality risk increased by 11% for pre-frailty and 39% for frailty. Frailty phenotypes were also dose-dependently associated with a higher risk of incidence and mortality of some site-specific cancers (including liver and lung), with significant sex differences. We observed a synergetic association of frailty phenotypes and smoking with overall cancer incidence and mortality risk. Frailty phenotypes contributed significantly to a higher risk of overall and some site-specific cancers incidence and mortality in a stepwise manner or within individual categories. Future studies are warranted to emphasize the identification, management and prevention of frailty in the whole population and complements of lifestyle-targeted interventions such as quitting smoking. • Evidence about the associations of frailty with cancer outcomes are insufficient. • Pre-frailty and frailty contributed to higher overall and site-specific cancer risks. • A synergetic effect between frailty phenotypes and smoking existed. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To examine trends in cancer mortality for migrants living in England and Wales. Method: The Office for National Statistics provided anonymised death records for 1979–1983, 1989–1993 and 1999–2003, and tabulated population data from the 1981, 1991 and 2001 censuses for England and Wales. Age-adjusted rates and rate ratios for 16 cancer sites were derived by country of birth and time period. Results: Compared with the declines for those born in England and Wales, smaller or non-significant declines in groups with historically low mortality lead to a pattern of convergence of rates towards those for England and Wales (e.g. breast cancer among women from the Caribbean or East Africa). However, for migrant groups with historically higher rates this had the effect of either maintaining or widening relative mortality (e.g. lung cancer among men from Republic of Ireland or Jamaica). Higher mortality among the Scots and Irish persisted for a range of cancers. Conclusion: In spite of general declines in cancer death rates, inequalities in migrant mortality remain. There is an urgent need for prevention and treatment programmes to maximise coverage across all minority groups. [Copyright &y& Elsevier]

Comparisons of survival rates of given diseases with different treatments or in different places often gave misleading results until the introduction of controlled trials. Recent reports of relatively low survival rates following the treatment of cancer in the UK compared to the rates in other countries, not based on controlled trials, may consequently be misleading. Their validity has, therefore, been tested by comparing the levels and trends in mortality--the ultimate criterion by which the success or failure of any system of care can be judged. For this purpose, rates and trends in rates over 20-50 years have been compared in five European countries of similar economic status (France, Italy, the Netherlands, Sweden, and the UK). The UK rates are not generally worse than those in the other countries and are sometimes better. Exceptions were cancer of the lung, large bowel, and breast, the first of which is explained by differences in the prevalence of smoking. [ABSTRACT FROM AUTHOR]

The mortality experienced by cohorts of 28 630 oil refinery workers and 16 480 petroleum distribution workers has been investigated. Study subjects were all those male employees first employed in the period 1946–1974 at one of eight UK oil refineries or at one of 476 UK petroleum distribution centres; all subjects had a minimum of 12 months employment with some employment after 1 January 1951. The observed numbers of cause‐specific deaths were compared with expectations based on national mortality rates. The resultant standardized mortality ratios (SMRs) were significantly below 100 for all causes, in both oil refinery workers (observed, 9341; expected, 10 649.7; SMR = 88) and petroleum distribution workers (observed, 6083; expected, 6460.3; SMR = 94). Significantly elevated SMRs were shown in oil refinery workers for cancer of the gall bladder (observed, 24; expected, 14.0; SMR = 172), cancer of the pleura (observed, 38; expected, 15.0; SMR = 254) and melanoma (observed, 36; expected, 22.2; SMR = 162). Significantly elevated SMRs were not found in petroleum distribution workers for any site of cancer. SMRs for selected causes of death were calculated by period from commencing employment, by year of hire and by job type. The only findings that suggested the presence of an occupational cancer hazard were an excess of mesothelioma in oil refinery workers and an excess of leukaemia in petroleum distribution workers, both excesses occurring in long‐term follow‐up for workers first employed >30 years ago. [ABSTRACT FROM PUBLISHER]

Background: Multimorbidity is associated with higher mortality, but the relationship with cancer and cardiovascular mortality is unclear. The influence of demographics and type of condition on the relationship of multimorbidity with mortality remains unknown. We examine the relationship between multimorbidity (number/type) and cause of mortality and the impact of demographic factors on this relationship.Methods: Data source: the UK Biobank; 500,769 participants; 37-73 years; 53.7% female. Exposure variables: number and type of long-term conditions (LTCs) (N = 43) at baseline, modelled separately. Cox regression models were used to study the impact of LTCs on all-cause/vascular/cancer mortality during median 7-year follow-up. All-cause mortality regression models were stratified by age/sex/socioeconomic status.Results: All-cause mortality is 2.9% (14,348 participants). Of all deaths, 8350 (58.2%) were cancer deaths and 2985 (20.8%) vascular deaths. Dose-response relationship is observed between the increasing number of LTCs and all-cause/cancer/vascular mortality. A strong association is observed between cardiometabolic multimorbidity and all three clinical outcomes; non-cardiometabolic multimorbidity (excluding cancer) is associated with all-cause/vascular mortality. All-cause mortality risk for those with ≥ 4 LTCs was nearly 3 times higher than those with no LTCs (HR 2.79, CI 2.61-2.98); for ≥ 4 cardiometabolic conditions, it was > 3 times higher (HR 3.20, CI 2.56-4.00); and for ≥ 4 non-cardiometabolic conditions (excluding cancer), it was 50% more (HR 1.50, CI 1.36-1.67). For those with ≥ 4 LTCs, morbidity combinations that included cardiometabolic conditions, chronic kidney disease, cancer, epilepsy, chronic obstructive pulmonary disease, depression, osteoporosis and connective tissue disorders had the greatest impact on all-cause mortality. In the stratified model by age/sex, absolute all-cause mortality was higher among the 60-73 age group with an increasing number of LTCs; however, the relative effect size of the increasing number of LTCs on higher mortality risk was larger among those 37-49 years, especially men. While socioeconomic status was a significant predictor of all-cause mortality, mortality risk with increasing number of LTCs remained constant across different socioeconomic gradients.Conclusions: Multimorbidity is associated with higher all-cause/cancer/vascular mortality. Type, as opposed to number, of LTCs may have an important role in understanding the relationship between multimorbidity and mortality. Multimorbidity had a greater relative impact on all-cause mortality in middle-aged as opposed to older populations, particularly males, which deserves exploration. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with familial hypercholesterolaemia (FH) have an elevated risk of coronary heart disease (CHD). Here we compare changes in CHD mortality in patients with heterozygous (FH) pre 1992, before lipid-lowering therapy with statins was used routinely, and in the periods 1992-2008 and 2008-2016., Methods: 1903 Definite (DFH) and 1650 Possible (PFH) patients (51% women) aged 20-79 years, recruited from 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2016 for 67,060 person-years. The CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (with 95% Confidence intervals)., Results: There were 585 deaths, including 252 from CHD. Overall, the observed 2.4-fold excess coronary mortality for treated DFH post-1991 was significantly higher than the 1.78 excess for PFH (35% 95% CI 3%-76%). In patients with DFH and established coronary disease, there was a significant excess coronary mortality in all time periods, but in men it was reduced from a 4.83-fold excess (2.32-8.89) pre-1992 to 4.66 (3.46-6.14) in 1992-2008 and 2.51 (1.01-5.17) post-2008, while in women the corresponding values were 7.23 (2.65-15.73), 4.42 (2.70-6.82) and 6.34 (2.06-14.81). Primary prevention in men with DFH resulted in a progressive reduction in coronary mortality over the three time-periods, with no excess mortality evident post-2008 (0.89 (0.29-2.08)), although in women the excess persisted (post-2008 3.65 (1.75-6.72))., Conclusions: The results confirm the benefit of statin treatment in reducing CHD mortality, but suggest that FH patients with pre-existing CHD and women with FH may not be treated adequately., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)