Trends in incidence, treatment and survival of Merkel cell carcinoma in England 2004-2018: a cohort study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare tumour with neuroendocrine differentiation and high associated mortality. Studies that describe the epidemiology of MCC are often limited by small sample size, short duration of follow-up, absence of nationwide data and paucity of data on different risk factors. OBJECTIVES: To determine the incidence, demographics and survival for MCC in England between 2004 and 2018. METHODS: This national retrospective cohort study identified all cases of MCC in England from 2004 to 2018 using national population-based data from the National Disease Registration Service. Crude counts, European age-standardized incidence rates (EASRs) and joinpoint analysis were conducted. Patient demographics and treatments received were described. Multivariable Cox regression analysis was used to study risk factors for MCC-specific mortality, by including a priori defined demographic factors, tumour characteristics and immunosuppression. Treatment data were not included in the Cox regression analysis. RESULTS: A total of 3775 MCC tumours were registered. The median age at diagnosis was 81 years (interquartile range 74-87). Overall, 96·6% of patients identified as White ethnicity, and 8·3% of patients were immunosuppressed. The most common site was the face (27·4%). Patients most often presented with stage one disease (22·8%); however, stage was unknown in 31·0%. In total, 80·7% of patients underwent surgical excision, 43·5% radiotherapy and 9·2% systemic therapy. The EASR increased from 0·43 per 100 000 person-years (PYs) to 0·65 per 100 000 person-years between 2004 and 2018, representing a significant annual percentage change of 3·9%. The EASR was greater in men than in women for all years, with an overall male-to-female ratio of 1·41 : 1. The highest EASR was in South West England. Five-year disease-specific survival was 65·6% [95% confidence interval (CI) 63·8-67·4], with a median follow-up of 767 days. MCC-specific mortality increased with age [hazard ratio (HR) 1·02, 95% CI 1·02-1·03], deprivation (HR 1·43, 95% CI 1·16-1·76), immunosuppression (HR 2·80, 95% CI 2·34-3·34) and stage at diagnosis (HR 8·24, 95% CI 5·84-11·6). CONCLUSIONS: This study presents the largest national MCC dataset in Europe, and the most complete reporting of MCC incidence and survival ever published. With the EASR of MCC increasing and high associated mortality, this study encourages further research into the pathology, diagnosis and therapeutic options for MCC to support management guidelines.

Changes in workplace car parking and commute mode: a natural experimental study.

BACKGROUND: The use of private motor vehicles places a considerable burden on public health. Changes in workplace car parking policies may be effective in shifting behaviour. We use a natural experimental design to assess whether changes in policy were associated with differences in commute mode. METHODS: We used cohort data from participants working in Cambridge (2009-2012). Commuters reported their trips and travel modes to work over the last week, workplace car parking policy and socioeconomic, environmental and health characteristics. Changes in policy were defined between phases (1608 transition periods; 884 participants). Using generalised estimating equations, we estimated associations between changes in parking policy and the proportion of trips that (i) were exclusively by motor vehicle, (ii) involved walking or cycling and (iii) involved public transport at follow-up. RESULTS: 25.1% of trips were made by motor vehicle, 54.6% involved walking or cycling and 11.7% involved public transport. The introduction of free or paid workplace parking was associated with higher proportions of motor vehicle trips (11.4%, 95% CI (6.4 to 16.3)) and lower proportions involving walking or cycling (-13.3%, 95% CI (-20.2 to -6.4)) and public transport (-5.8%, 95% CI (-10.6 to -0.9)) compared with those with no workplace parking. Restrictive changes in policy were associated with shifts in the expected direction but these were not statistically significant. CONCLUSION: Relaxation of parking policy was associated with higher proportions of trips made by motor vehicle. Further longitudinal and intervention research is required to assess generalisability of these findings.

Changes in the mode of travel to work and the severity of depressive symptoms: a longitudinal analysis of UK Biobank.

Although commuting provides an opportunity for incorporating physical activity into daily routines, little is known about the effect of active commuting upon depressive symptoms. This study aimed to determine whether changes in commute mode are associated with differences in the severity of depressive symptoms in working adults. Commuters were selected from the UK Biobank cohort if they completed ≥2 assessment centre visits between 2006 and 2016. Modes of travel to work were self-reported at each visit. Participants were categorised as 'inactive' (car only) or 'active' commuters (any other mode(s), including walking, cycling and public transport). Transitions between categories were defined between pairs of visits. The severity of depressive symptoms was defined using the two-item Patient Health Questionnaire (PHQ-2). Scores were derived between zero and six. Higher values indicate more severe symptoms. Separate analyses were conducted in commuters who were asymptomatic (zero score) and symptomatic (non-zero score) at baseline. The analytical sample comprised 5474 participants aged 40-75 at baseline with a mean follow-up of 4.65 years. Asymptomatic commuters who transitioned from inactive to active commuting reported less severe symptoms at follow-up than those who remained inactive (ß -0.10, 95% CI [-0.20, 0.00]; N = 3145). A similar but non-significant relationship is evident among commuters with pre-existing symptoms (ß -0.60, 95% CI [-1.27, 0.08]; N = 1078). After adjusting for transition category, longer commutes at baseline were associated with worse depressive symptoms at follow-up among symptomatic participants. Shifting from exclusive car use towards more active commuting may help prevent and attenuate depressive symptoms in working adults.

Trajectories of alcohol consumption prior to the diagnosis of type 2 diabetes: a longitudinal case-cohort study.

BACKGROUND: Non-linear associations have been reported between baseline measures of alcohol consumption and type 2 diabetes (T2DM). However, given that drinking varies over the adult life course, we investigated whether differences existed in the longitudinal trajectory of alcohol consumption according to T2DM status. METHODS: For a case-cohort (916 incident cases; 7376 controls) of British civil servants nested within the Whitehall II cohort, the self-reported weekly volume of alcohol consumption was traced backwards from the date of diagnosis or censoring to the beginning of the study, covering a period of up to 28 years. Mean trajectories of alcohol intake were estimated separately by diagnosis status using random-effects models. RESULTS: Drinking increased linearly among male cases before diagnosis, but declined among male non-cases prior to censoring. At the time of diagnosis or censoring, consumption among those who developed T2DM was 33.4 g/week greater on average. These patterns were not apparent among women. Here, alcohol intake among female cases was consistently below that of non-cases, with the difference in consumption most pronounced around 15 years prior to diagnosis or censoring, at ∼28.0 g/week. Disparities by diagnosis status were attenuated following adjustment for potential confounders, including the frequency of consumption and metabolic factors. Drinking among male and female cases declined following diagnosis. CONCLUSIONS: Differences in the weekly volume of alcohol consumption are reported in the years leading up to diagnosis or censoring. Although male and female cases predominantly consumed alcohol at volumes lower than or equal to those who were not diagnosed, these disparities appear to be largely explained by a range of socio-demographic and lifestyle factors. Where disparities are observed between cases and non-cases, adjusted absolute differences are small in magnitude. The decision to drink alcohol should not be motivated by a perceived benefit to T2DM risk.

The stability of baseline-defined categories of alcohol consumption during the adult life-course: a 28-year prospective cohort study.

BACKGROUND AND AIMS: Studies that report the relationship between alcohol consumption and disease risk have predominantly operationalized drinking according to a single baseline measure. The resulting assumption of longitudinal stability may be simplistic and complicate interpretation of risk estimates. This study aims to describe changes to the volume of consumption during the adult life-course according to baseline categories of drinking. DESIGN: A prospective observational study. SETTING: United Kingdom. PARTICIPANTS: A cohort of British civil servants totalling 6838 men and 3372 women aged 34-55 years at baseline, followed for a mean 19.1 (standard deviation = 9.5) years. MEASUREMENTS: The volume of weekly alcohol consumption was estimated from data concerning the frequency and number of drinks consumed. Baseline categories were defined: non-current drinkers, infrequent drinkers, 0.1-50.0 g/week, 50.1-100.0 g/week, 100.1-150.0 g/week, 150.1-250.0 g/week and >250.0 g/week. For women, the highest category was defined as > 100.0 g/week. Baseline frequency was derived as 'daily or almost daily' and 'not daily or almost daily'. Trajectories were estimated within baseline categories using growth curve models. FINDINGS: Trajectories differed between men and women, but were relatively stable within light-to-moderate categories of baseline consumption. Drinking was least stable within the highest categories of baseline consumption (men: > 250.0 g/week; women: > 100.0 g/week), declining by 47.0 [95% confidence interval (CI) = 40.7, 53.2] and 16.8 g/week (95% CI = 12.6, 21.0), respectively, per 10-year increase in age. These declines were not a consequence of sudden transitions to complete abstention. Rates of decline appear greatest in older age, with trajectories converging toward moderate volumes. CONCLUSION: Among UK civil servants, consumption within baseline drinking categories is generally stable during the life-course, except among heavier baseline drinkers, for whom intakes decline with increasing age. This shift does not appear to be driven by transitions to non-drinking. Cohorts of older people may be at particular risk of misclassifying former heavy drinkers as moderate consumers of alcohol.

All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts.

OBJECTIVES: To examine the suitability of age specific limits for alcohol consumption and to explore the association between alcohol consumption and mortality in different age groups. DESIGN: Population based data from Health Survey for England 1998-2008, linked to national mortality registration data and pooled for analysis using proportional hazards regression. Analyses were stratified by sex and age group (50-64 and ≥ 65 years). SETTING: Up to 10 waves of the Health Survey for England, which samples the non-institutionalised general population resident in England. PARTICIPANTS: The derivation of two analytical samples was based on the availability of comparable alcohol consumption data, covariate data, and linked mortality data among adults aged 50 years or more. Two samples were used, each utilising a different variable for alcohol usage: self reported average weekly consumption over the past year and self reported consumption on the heaviest day in the past week. In fully adjusted analyses, the former sample comprised Health Survey for England years 1998-2002, 18,368 participants, and 4102 deaths over a median follow-up of 9.7 years, whereas the latter comprised Health Survey for England years 1999-2008, 34,523 participants, and 4220 deaths over a median follow-up of 6.5 years. MAIN OUTCOME MEASURE: All cause mortality, defined as any death recorded between the date of interview and the end of data linkage on 31 March 2011. RESULTS: In unadjusted models, protective effects were identified across a broad range of alcohol usage in all age-sex groups. These effects were attenuated across most use categories on adjustment for a range of personal, socioeconomic, and lifestyle factors. After the exclusion of former drinkers, these effects were further attenuated. Compared with self reported never drinkers, significant protective associations were limited to younger men (50-64 years) and older women (≥ 65 years). Among younger men, the range of protective effects was minimal, with a significant reduction in hazards present only among those who reported consuming 15.1-20.0 units/average week (hazard ratio 0.49, 95% confidence interval 0.26 to 0.91) or 0.1-1.5 units on the heaviest day (0.43, 0.21 to 0.87). The range of protective effects was broader but lower among older women, with significant reductions in hazards present ≤ 10.0 units/average week and across all levels of heaviest day use. Supplementary analyses found that most protective effects disappeared where calculated in comparison with various definitions of occasional drinkers. CONCLUSIONS: Beneficial associations between low intensity alcohol consumption and all cause mortality may in part be attributable to inappropriate selection of a referent group and weak adjustment for confounders. Compared with never drinkers, age stratified analyses suggest that beneficial dose-response relations between alcohol consumption and all cause mortality may be largely specific to women drinkers aged 65 years or more, with little to no protection present in other age-sex groups. These protective associations may, however, be explained by the effect of selection biases across age-sex strata.

Association between alcohol calorie intake and overweight and obesity in English adults.

We investigated the contribution of alcohol-derived calories to the alcohol-obesity relation. Adult alcohol calorie intake was derived from consumption volume and drink type in the Health Survey for England 2006 (n = 8864). We calculated the odds of obesity with survey-adjusted logistic regression. Mean alcohol calorie consumption was 27% of the recommended daily calorie intake in men and 19% in women on the heaviest drinking day in the last week, with a positive association between alcohol calories and obesity. Alcohol calories may be a significant contributor to the rise in obesity.

Could more than three million older people in England be at risk of alcohol-related harm? A cross-sectional analysis of proposed age-specific drinking limits.

OBJECTIVE: to determine the impact of recently proposed age-specific alcohol consumption limits on the proportion and number of older people classified at risk of alcohol-related harm. DESIGN: nationally representative cross-sectional population data from the Health Survey for England (HSE). PARTICIPANTS: adults with valid alcohol consumption data, comprising 14,718 participants from 2003 and 14,939 from 2008. MAIN OUTCOME MEASURE: the prevalence of alcohol consumption in excess of existing and recently proposed consumption limits, plus associated population estimates. RESULTS: the number of individuals aged 65 or over and drinking in excess of daily recommended limits would have increased 2.5-fold to over 3 million in 2008 under age-specific recommendations proposed in a report from the Royal College of Psychiatrists, equating to an at-risk population 809,000 individuals greater than found within the 16-24 age group during the same year. Suggested revisions to existing binge drinking classifications would have defined almost 1,200,000 people aged 65 or over as hazardous consumers of alcohol in 2008-a 3.6-fold increase over existing definitions. CONCLUSION: age-specific drinking recommendations proposed in the Royal College of Psychiatrists Report would increase the number of older drinkers classified as hazardous alcohol consumers to a level greater than found among young adults aged 16-24.