Dataset Information

The epidemiology of regular opioid use and its association with mortality: Prospective cohort study of 466 486 UK biobank participants.

ABSTRACT:

Background

Opioids have, at most, small benefits for non-cancer pain in the medium and long-term but there is good evidence that they cause harm. The current study describes the characteristics and clinical status of people taking regular opioids in Great Britain and determines whether use is associated with mortality risk.

Methods

An analysis of participants in UK Biobank, a prospective population-based study. At recruitment (2006-10) participants reported medicines which they regularly used in addition to lifestyle and health-related factors. Information was available on deaths until October 2016.

Findings

There were 466 486 participants (54% women) aged 40-69 years and without a prior history of cancer of whom 5.5% were regularly using opioids. Use increased with age-group, was more common in females (6.3% v. 4.6%) and 87% of persons using them reported chronic pain. The highest rates of use (~1 in 9) were in people with low household income, who left school <16 years and lived in areas with high deprivation. Amongst 15,032 people who could not work because of ill-health, 1 in 3 were regularly taking opioids. Regular users reported insomnia (88.7%), a recent major recent life event (57.3%) and were much more likely than non-users to rate their health as poor (RR 5.5, 99% CI (4.9, 6.1)). Those taking weak (4.2% of participants) or strong (1.4%) opioids were more likely to die during follow-up (6.9% and 9.1% respectively v. 3.3% in non-users) an excess which remained after adjustment for demographic, socio-economic, health and lifestyle factors (MRR 1.18 99% CI (1.06, 1.32) and 1.20 99% CI (1.01, 1.43)) respectively.

Interpretation

Regular use of opioids is common in Great Britain, particularly in groups of low socio-economic status. Most users still report chronic pain, poor health generally and are at increased risk of premature death although it is not established that this relationship is causal.

Funding

There were no external sources of funding obtained for the current analyses.

SUBMITTER: Macfarlane GJ

PROVIDER: S-EPMC7170951 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundFollowing a vegetarian diet has become increasingly popular and some evidence suggests that being vegetarian may be associated with a lower risk of cancer overall. However, for specific cancer sites, the evidence is limited. Our aim was to assess the associations of vegetarian and non-vegetarian diets with risks of all cancer, colorectal cancer, postmenopausal breast cancer, and prostate cancer and to explore the role of potential mediators between these associations.MethodsWe conducted a prospective analysis of 472,377 UK Biobank participants who were free from cancer at recruitment. Participants were categorised into regular meat-eaters (n = 247,571), low meat-eaters (n = 205,385), fish-eaters (n = 10,696), and vegetarians (n = 8685) based on dietary questions completed at recruitment. Multivariable-adjusted Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all cancer incidence and separate cancer sites across diet groups.ResultsAfter an average follow-up of 11.4 years, 54,961 incident cancers were identified, including 5882 colorectal, 7537 postmenopausal breast, and 9501 prostate cancers. Compared with regular meat-eaters, being a low meat-eater, fish-eater, or vegetarian were all associated with a lower risk of all cancer (HR: 0.98, 95% CI: 0.96-1.00; 0.90, 0.84-0.96; 0.86, 0.80-0.93, respectively). Being a low meat-eater was associated with a lower risk of colorectal cancer in comparison to regular meat-eaters (0.91, 0.86-0.96); however, there was heterogeneity in this association by sex (p = 0.007), with an inverse association across diet groups in men, but not in women. Vegetarian postmenopausal women had a lower risk of breast cancer (0.82, 0.68-0.99), which was attenuated and non-significant after adjusting for body mass index (BMI; 0.87, 0.72-1.05); in mediation analyses, BMI was found to possibly mediate the observed association. In men, being a fish-eater or a vegetarian was associated with a lower risk of prostate cancer (0.80, 0.65-0.99 and 0.69, 0.54-0.89, respectively).ConclusionThe lower risk of colorectal cancer in low meat-eaters is consistent with previous evidence suggesting an adverse impact of meat intake. The lower risk of postmenopausal breast cancer in vegetarian women may be explained by their lower BMI. It is not clear whether the other differences observed for all cancers and for prostate cancer reflect any causal relationships or are due to other factors such as residual confounding or differences in cancer detection.

Project description:OBJECTIVE:To investigate the association of macronutrient intake with all cause mortality and cardiovascular disease (CVD), and the implications for dietary advice. DESIGN:Prospective population based study. SETTING:UK Biobank. PARTICIPANTS:195 658 of the 502 536 participants in UK Biobank completed at least one dietary questionnaire and were included in the analyses. Diet was assessed using Oxford WebQ, a web based 24 hour recall questionnaire, and nutrient intakes were estimated using standard methodology. Cox proportional models with penalised cubic splines were used to study non-linear associations. MAIN OUTCOME MEASURES:All cause mortality and incidence of CVD. RESULTS:4780 (2.4%) participants died over a mean 10.6 (range 9.4-13.9) years of follow-up, and 948 (0.5%) and 9776 (5.0%) experienced fatal and non-fatal CVD events, respectively, over a mean 9.7 (range 8.5-13.0) years of follow-up. Non-linear associations were found for many macronutrients. Carbohydrate intake showed a non-linear association with mortality; no association at 20-50% of total energy intake but a positive association at 50-70% of energy intake (3.14 v 2.75 per 1000 person years, average hazard ratio 1.14, 95% confidence interval 1.03 to 1.28 (60-70% v 50% of energy)). A similar pattern was observed for sugar but not for starch or fibre. A higher intake of monounsaturated fat (2.94 v 3.50 per 1000 person years, average hazard ratio 0.58, 0.51 to 0.66 (20-25% v 5% of energy)) and lower intake of polyunsaturated fat (2.66 v 3.04 per 1000 person years, 0.78, 0.75 to 0.81 (5-7% v 12% of energy)) and saturated fat (2.66 v 3.59 per 1000 person years, 0.67, 0.62 to 0.73 (5-10% v 20% of energy)) were associated with a lower risk of mortality. A dietary risk matrix was developed to illustrate how dietary advice can be given based on current intake. CONCLUSION:Many associations between macronutrient intake and health outcomes are non-linear. Thus dietary advice could be tailored to current intake. Dietary guidelines on macronutrients (eg, carbohydrate) should also take account of differential associations of its components (eg, sugar and starch).

Project description:Study questionWhat is the association between menopausal hormone therapy (MHT) and cause-specific mortality?Summary answerSelf-reported MHT use following early natural menopause, surgical menopause or premenopausal hysterectomy is associated with a lower risk of breast cancer mortality and is not consistently associated with the risk of mortality from cardiovascular disease or other causes.What is known alreadyEvidence from the Women's Health Initiative randomized controlled trials showed that the use of estrogen alone is not associated with the risk of cardiovascular mortality and is associated with a lower risk of breast cancer mortality, but evidence from the Million Women Study showed that use of estrogen alone is associated with a higher risk of breast cancer mortality.Study design, size, durationCohort study (the UK Biobank), 178 379 women, recruited in 2006-2010.Participants/materials, setting, methodsPostmenopausal women who had reported age at menopause (natural or surgical) or hysterectomy, and information on MHT and cause-specific mortality. Age at natural menopause, age at surgical menopause, age at hysterectomy and MHT were exposures of interest. Natural menopause was defined as spontaneous cessation of menstruation for 12 months with no previous hysterectomy or oophorectomy. Surgical menopause was defined as the removal of both ovaries prior to natural menopause. Hysterectomy was defined as removal of the uterus before natural menopause without bilateral oophorectomy. The study outcome was cause-specific mortality.Main results and the role of chanceAmong the 178 379 women included, 136 790 had natural menopause, 17 569 had surgical menopause and 24 020 had hysterectomy alone. Compared with women with natural menopause at the age of 50-52 years, women with natural menopause before 40 years (hazard ratio (HR): 2.38, 95% CI: 1.64, 3.45) or hysterectomy before 40 years (HR: 1.60, 95% CI: 1.23, 2.07) had a higher risk of cardiovascular mortality but not cancer mortality. MHT use was associated with a lower risk of breast cancer mortality following surgical menopause before 45 years (HR: 0.17, 95% CI: 0.08, 0.36), at 45-49 years (HR: 0.15, 95% CI: 0.07, 0.35) or at ≥50 years (HR: 0.28, 95% CI: 0.13, 0.63), and the association between MHT use and the risk of breast cancer mortality did not differ by MHT use duration (<6 or 6-20 years). MHT use was also associated with a lower risk of breast cancer mortality following natural menopause before 45 years (HR: 0.59, 95% CI: 0.36, 0.95) or hysterectomy before 45 years (HR: 0.49, 95% CI: 0.32, 0.74).Limitations, reasons for cautionSelf-reported data on age at natural menopause, age at surgical menopause, age at hysterectomy and MHT.Wider implications of the findingsThe current international guidelines recommend women with early menopause to use MHT until the average age at menopause. Our findings support this recommendation.Study funding/competing interest(s)This project is funded by the Australian National Health and Medical Research Council (NHMRC) (grant numbers APP1027196 and APP1153420). G.D.M. is supported by NHMRC Principal Research Fellowship (APP1121844), and M.H. is supported by an NHMRC Investigator Grant (APP1193838). There are no competing interests.Trial registration numberN/A.

Project description:BackgroundPlasma metabolomic profile is disturbed in dementia patients, but previous studies have discordant conclusions.MethodsCirculating metabolomic data of 110,655 people in the UK Biobank study were measured with nuclear magnetic resonance technique, and incident dementia records were obtained from national health registers. The associations between plasma metabolites and dementia were estimated using Cox proportional hazard models. The 10-fold cross-validation elastic net regression models selected metabolites that predicted incident dementia, and a 10-year prediction model for dementia was constructed by multivariable logistic regression. The predictive values of the conventional risk model, the metabolites model, and the combined model were discriminated by comparison of area under the receiver operating characteristic curves (AUCs). Net reclassification improvement (NRI) was used to estimate the change of reclassification ability when adding metabolites into the conventional prediction model.ResultsAmongst 110,655 participants, the mean (standard deviation) age was 56.5 (8.1) years, and 51 186 (46.3%) were male. A total of 1439 (13.0%) developed dementia during a median follow-up of 12.2 years (interquartile range: 11.5-12.9 years). A total of 38 metabolites, including lipids and lipoproteins, ketone bodies, glycolysis-related metabolites, and amino acids, were found to be significantly associated with incident dementia. Adding selected metabolites (n=24) to the conventional dementia risk prediction model significantly improved the prediction for incident dementia (AUC: 0.824 versus 0.817, p =0.042) and reclassification ability (NRI = 4.97%, P = 0.009) for identifying high risk groups.ConclusionsOur analysis identified various metabolomic biomarkers which were significantly associated with incident dementia. Metabolomic profiles also provided opportunities for dementia risk reclassification. These findings may help explain the biological mechanisms underlying dementia and improve dementia prediction.

Project description:BackgroundRegular stair climbing has the potential to lower the risk of premature death, but current evidence is scarce. We aimed to examine whether daily stair climbing is associated with lower risk of all-cause, cancer, and cardiovascular disease (CVD) mortality.MethodsUsing the UK Biobank cohort, we extracted information of self-reported daily flights of stairs climbed at home, categorized as none, 1 to 5, 6 to 10, 11 to 15, and ≥16 flights per day. Associations between flights of stair climbed per day and mortality were examined as hazard ratios (HRs) from Cox proportional hazards models adjusted for demographic, clinical, and behavioural covariates including time spent in other physical activities. We calculated the restricted mean survival time as an absolute measure of association. The risk of residual confounding was examined using propensity score matching and by using lung cancer as negative control outcome. Participants were followed from baseline (2006-2010) through 31 March 2020.ResultsA total of 280 423 participants (median follow-up 11.1 years, during which 9445 deaths occurred) were included. Compared with not climbing any stairs, climbing more than five flights of stairs at home per day was associated with lower risk of premature mortality. The lowest risk was found for those climbing 6-10 flights per day: 0.91; 95% confidence interval (CI): 0.85, 0.98, translated to approximately 44 to 55 days of additional survival. A similar pattern was found after applying propensity score matching and for cancer mortality (6-10 flights per day HR: 0.88; 95% CI: 0.80, 0.97), but not for CVD mortality (6-10 flights per day HR: 1.08; 95% CI: 0.91, 1.29). The association between stair climbing and lung cancer was similar to that of all-cause mortality.ConclusionsClimbing more than five flights of stairs at home per day was associated with a lower risk of all-cause and cancer mortality, but not CVD mortality, compared with those who did not take the stairs. The magnitude of the association was small and appeared susceptible to residual confounding. It is unlikely that at-home stair climbing is sufficient physical activity stimuli to lower the risk of premature mortality.