Underlying pathways of social inequality in tooth loss: the mediating role of sugary beverages and diabetes.

BACKGROUND: Previous studies show social inequality in tooth loss, but the underlying pathways are not well understood. The aim was to investigate the mediated proportion of sugary beverages (SBs) and diabetes and the association between educational level and tooth loss, and to investigate whether the indirect effect of SBs and diabetes varied between educational groups in relation to tooth loss. METHODS: Data from 47,109 Danish men and women aged 50 years or older included in the Danish Diet, Cancer and Health Study was combined with data from Danish registers. Using natural effect models, SBs and diabetes were considered as mediators, and tooth loss was defined as having <15 teeth present. RESULTS: In total, 10,648 participants had tooth loss. The analyses showed that 3% (95% confidence interval 2-4%) of the social inequality in tooth loss was mediated through SBs and diabetes. The mediated proportion was mainly due to differential exposure to SBs and diabetes among lower educational groups. CONCLUSIONS: The findings show that SBs and diabetes to a minor degree contribute to tooth-loss inequalities. The explanation indicates that individuals in lower educational groups have higher consumption of SBs and more often suffer from diabetes than higher educational groups.

Social position and functional somatic disorders: The DanFunD study.

BACKGROUND AND AIM: It is generally accepted that functional somatic disorders (FSDs) are a product of biological, psychological, and social factors. Social position might be part of this complex, but the literature on this issue is currently heterogeneous and inconsistent. The aim of the present study was - in a population-based cohort - to test the hypothesis that lower social position would be associated with higher a risk of FSD. METHOD: The association between social position and FSD was examined in a cross-sectional study with various measures of social position (education as measured by vocational training; employment; cohabitation; subjective social status) and delimitations of FSD (irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, bodily distress syndrome, and symptom profiles). The associations were analyzed using logistic regressions to calculate odds ratios and 95% confidence intervals. Each social measure was analyzed independently and was adjusted for age and sex. RESULTS: Lower levels of vocational training, being unemployed, and living alone were associated with higher risk of FSD, regardless of the FSD delimitation. There was also a significant negative association between subjective evaluated social status and FSD. The associations remained after multiple adjustments, and seemed to be strongest for the more severe FSD-types. CONCLUSIONS: Lower social position is associated with higher risk of FSD, especially the more severe FSD delimitations, which might constitute an especially vulnerable group. However, the mechanisms behind the relations remain unknown.

Sedative drug-use in Denmark, 2000 to 2019: a nationwide drug utilization study.

AIM: To describe trends in and characteristics of sedative drug use from 2000 through 2019 in relation to the introduction of central regulations and new drugs. METHODS: In this descriptive study, we used individual prescription data on the entire Danish population from the Danish National Prescription Registry to calculate yearly incidence and prevalence of use of benzodiazepines, benzodiazepine-related drugs (Z-drugs), melatonin, olanzapine, low-dose quetiapine, mianserin/mirtazapine, pregabalin, and promethazine from 2000 through 2019. From the Danish National Patient Registry, we obtained data on drug users' psychiatric and somatic comorbidity. RESULTS: The use of benzodiazepines and Z-drugs declined gradually from 2000 through 2019, whereas the newer alternatives, melatonin, low-dose quetiapine, pregabalin and promethazine, increased in use, while the use of olanzapine and mianserin/mirtazapine was relatively stable. This development was seen in both men and women and across all age groups except for hypnotic benzodiazepines which showed a steep increase in the oldest age group from 2010. For all sedative drugs depression, anxiety, alcohol and misuse disorder, pain and cancer were the most prevalent comorbidities. During our study period, the number of individuals without any of the selected diagnoses increased. CONCLUSION: In Denmark different central regulations have influenced prescription practice toward more restrictive use of Z-drugs and benzodiazepines, except for hypnotic benzodiazepine prescriptions increased after the introduction of special palliative care. An increase in use of newer sedative drugs, however, indicates that the regulations do not remove the need for sedative drugs in the population.

Association of Hormone Therapy With Depression During Menopause in a Cohort of Danish Women.

Importance: During menopause, the levels of estrogen and progesterone decrease and 60% to 70% of women experience menopausal symptoms, including mood disturbances. The latter might be prevented by hormone therapy (HT), yet some studies have suggested that use of HT might be associated with increased risk of depression. Objective: To examine whether use of HT during menopause was associated with a subsequent diagnosis of depression. Design, Setting, and Participants: This nationwide register-based cohort and self-controlled case series study included all women in Denmark aged 45 years between January 1, 1995, through December 31, 2017 (n = 825 238), without prior oophorectomy, breast cancer, or cancer in reproductive organs. Follow-up was completed on December 31, 2018. The statistical analysis was performed from September 1, 2021, through May 31, 2022. Exposures: Redeemed prescriptions of different types of HT identified by the Anatomical Therapeutic Chemical classification system codes (G03C [estrogen] and G03F [estrogen combined with progestin]) in the Danish National Prescription Registry between 1995 and 2017. Type of administration was divided into systemic (oral or transdermal) and local (intravaginal or intrauterine). Main Outcomes and Measures: A hospital diagnosis of depression (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes F32-F33 and International Classification of Diseases, Eighth Revision, codes 296.09, 296.29, 298.0, and 300.49) between 1995 through 2018. Associations were examined in cohort and self-controlled case series analysis using Cox proportional hazards and fixed-effects Poisson regression models. Results: During follow-up from 45 years of age to a mean of 56.0 (range, 45.1-67.7) years, 189 821 women (23.0%) initiated systemically or locally administered HT and 13 069 (1.6%) were diagnosed with depression. Systemically administered HT was mainly initiated before 50 years of age and was associated with a higher risk of a subsequent depression diagnosis (hazard ratio [HR] for 48-50 years of age, 1.50 [95% CI, 1.24-1.81]). The risk was especially elevated the year after initiation of both treatment with estrogen alone (HR, 2.03 [95% CI, 1.21-3.41]) and estrogen combined with progestin (HR, 2.01 [95% CI,1.26-3.21]). Locally administered HT was initiated across all ages and was not associated with depression risk (HR, 1.15 [95% CI, 0.70-1.87]). It was, however, associated with a lower risk of depression when initiated after 54 years of age (HR for 54-60 years of age, 0.80 [95% CI, 0.70-0.91]). In self-controlled analysis, which efficiently accounts for time-invariant confounding, users of systemically administered HT had higher rates of depression in the years after initiation compared with the years before treatment (incidence rate ratio for 0-1 year after initiation, 1.66 [95% CI, 1.30-2.14]). Conclusions and Relevance: These findings suggest that systemically administered HT before and during menopause is associated with higher risk of depression, especially in the years immediately after initiation, whereas locally administered HT is associated with lower risk of depression for women 54 years or older.

Use of GLP-1 receptor agonists and subsequent risk of alcohol-related events. A nationwide register-based cohort and self-controlled case series study.

Animal studies have related glucagon-like peptide 1 receptor agonists (GLP-1) to lower alcohol intake. We examined whether GLP-1 was associated with risk of alcohol-related events in a nationwide cohort study and a self-controlled case series analysis including all new users of GLP1 (n = 38 454) and dipeptidyl peptidase 4 inhibitors (DPP4) (n = 49 222) in Denmark 2009-2017. They were followed for hospital contacts with alcohol use disorder or purchase of drugs for treatment of alcohol dependence in nationwide registers from 2009 to 2018. Associations were examined using Cox proportional hazard and conditional Poisson regression. During follow-up of median 4.1 years, 649 (0.7%) of participants were registered with an alcohol-related event. Initiation of GLP-1 treatment was associated with lower risk of an alcohol-related event (Hazard ratio = 0.46 (95%CI: 0.24-0.86) compared with initiation of DPP4 during the first 3 months of follow-up. Self-controlled analysis showed the highest risk of alcohol-related events in the 3-month pretreatment period (incidence rate ratio [IRR] = 1.25 (1.00-1.58)), whereas the risk was lowest in the first 3-month treatment period (IRR = 0.74 (0.56-0.97). In conclusion, compared with DPP4 users, individuals who start treatment with GLP-1 had lower incidence of alcohol-related events both in cohort and self-controlled analyses. Thus, there might be a transient preventive effect of GLP1 on alcohol-related events the first months after treatment initiation.

Socioeconomic disparity in cardiovascular disease: Possible biological pathways based on a proteomic approach.

BACKGROUND AND AIMS: Large social disparities in the occurrence of cardiovascular disease (CVD) have been documented but the underlying biological mechanisms are largely unknown. We investigated a panel of biomarkers linked to CVD to improve our understanding and quantify the biological pathways in socioeconomic disparity in CVD and their mediation through behavioural and biological risk factors. METHODS: We included 1142 participants from the Copenhagen City Heart Study aged 55-64 years. Socioeconomic position (SEP) was defined by the length of education and household income. Blood samples were analysed for 184 biomarkers (Olink). Pearson's correlation analysis and linear regression with multivariate adjustment for CVD risk factors were performed. RESULTS: The median length of education was 10 (IQR 7-11) years and associated with age, sex, BMI, smoking, blood pressure, physical activity and income. 48 biomarkers were significantly correlated (p < 0.05) to the length of education. The strongest negative associations were seen for interleukin-6 (IL-6), metalloproteinase 12, growth/differentiation factor 15 (GDF-15), retinoic acid receptor responder protein 2 (RARRES2), leptin (LEP), von Willebrand factor (vWF), and renin (REN) (all p < 0.0001) while the strongest positive associations were seen for chymotrypsin, paraoxonase, epidermal growth factor receptor (EGFR) and brother of CDO (cell adhesion and platelet activation) (all p < 0.001). Proportion mediated by CVD risk factors ranged from <1% to 100%. After multivariate adjustment, 14 biomarkers remained significantly associated with education. CONCLUSIONS: SEP was associated with multiple biomarkers, indicating pathways involving inflammation (IL-6, RARRES2), platelet-activation (vWF, IL-6), blood pressure (REN, LEP) and Mitogen-activated protein kinase cascade (GDF-15, EGFR) may contribute to the socioeconomic differences in CVD.

An analysis of the relative and absolute incidence of somatic morbidity in patients with affective disorders-A nationwide cohort study.

BACKGROUND: Patients with affective disorder seem to experience higher risks of several somatic diseases, but no studies have provided estimates of both absolute and relative risks for these diseases in the same population. METHODS: A prospective cohort of all patients age ≥18 years old with a hospital contact with affective disorder between 1997-2014 (n=246,282) and a random sample from the background population (n=167,562) was followed for hospitalizations with cardiovascular disease, diabetes, cancers, chronic obstructive pulmonary disease (COPD), asthma, inflammatory bowel disease, hip fracture, psoriasis, migraine, or dementia. Adjusted absolute and relative risk estimates were calculated using multivariable adjusted Aalen's additive and Cox proportional hazard regression models. RESULTS: After adjustments, the absolute risk difference was 130.6 (95% confidence interval [CI] 125.5-135.7) additional cases per 10,000 person-years among affective disorder patients compared to the reference population. The corresponding hazard ratio for any somatic disease was 1.50 (95% CI 1.48-1.52). The strongest associations were found for dementia, hip fracture, COPD, and stroke on both the relative and absolute scale. The patients did not have higher risk of cancers except for lung cancer and brain tumors. Risk estimates tended to be slightly higher for individuals with depression or other affective disorder compared to bipolar disorder. LIMITATIONS: Limitations include use of register-based data, risk of reverse causation and Berkson's bias. CONCLUSIONS: Patients with affective disorder have both higher absolute and relative risk of most somatic diseases except for cancers. Further identification of the shared mechanisms will facilitate the development of targeted interventions.

Possible Modifiers of the Association Between Change in Weight Status From Child Through Adult Ages and Later Risk of Type 2 Diabetes.

OBJECTIVE: We investigated the association between changes in weight status from childhood through adulthood and subsequent type 2 diabetes risks and whether educational attainment, smoking, and leisure time physical activity (LTPA) modify this association. RESEARCH DESIGN AND METHODS: Using data from 10 Danish and Finnish cohorts including 25,283 individuals, childhood BMI at 7 and 12 years was categorized as normal or high using age- and sex-specific cutoffs (<85th or ≥85th percentile). Adult BMI (20-71 years) was categorized as nonobese or obese (<30.0 or ≥30.0 kg/m2, respectively). Associations between BMI patterns and type 2 diabetes (989 women and 1,370 men) were analyzed using Cox proportional hazards regressions and meta-analysis techniques. RESULTS: Compared with individuals with a normal BMI at 7 years and without adult obesity, those with a high BMI at 7 years and adult obesity had higher type 2 diabetes risks (hazard ratio [HR]girls 5.04 [95% CI 3.92-6.48]; HRboys 3.78 [95% CI 2.68-5.33]). Individuals with a high BMI at 7 years but without adult obesity did not have a higher risk (HRgirls 0.74 [95% CI 0.52-1.06]; HRboys 0.93 [95% CI 0.65-1.33]). Education, smoking, and LTPA were associated with diabetes risks but did not modify or confound the associations with BMI changes. Results for 12 years of age were similar. CONCLUSIONS: A high BMI in childhood was associated with higher type 2 diabetes risks only if individuals also had obesity in adulthood. These associations were not influenced by educational and lifestyle factors, indicating that BMI is similarly related to the risk across all levels of these factors.

Chronic Diseases in High-Cost Users of Hospital, Primary Care, and Prescription Medication in the Capital Region of Denmark.

BACKGROUND: A small proportion of patients account for the majority of health care costs. This group is often referred to as high-cost users (HCU). A frequently described characteristic of HCU is chronic disease. Yet, there is a gap in understanding the economic burden of chronic diseases associated with HCU to different types of health care services. OBJECTIVE: To analyze which frequent chronic diseases have the strongest association with HCU overall, and HCU in hospital, primary care, and prescription medication. DESIGN: This is a register-based observational study on Danish health service costs for various diseases in different medical settings. PARTICIPANTS: A total of 1,350,677 individuals aged ≥ 18 years living in the Capital Region of Denmark by 1 January 2012 were included. MAIN MEASURES: Chronic diseases, costs, and sociodemographic data were extracted from the nationwide registers, including data from hospitals, primary care, and medicine consumption. These information were merged on an individual level. KEY RESULTS: Cancer, mental disorders except depression, and heart diseases have the strongest association with HCU overall. Mental disorders except depression were in the three diseases most prevalent in HCU in all the three health care services. CONCLUSIONS: Our results show that the chronic diseases that have the strongest association with HCU differ between different types of health care services. Our findings may be helpful in informing future policies about health care organization and may guide to different prevention, treatment, and rehabilitation strategies that could lessen the burden in the hospital.

Intelligence Test Scores Before and After Alcohol-Related Disorders-A Longitudinal Study of Danish Male Conscripts.

BACKGROUND: Existing studies on intellectual consequences of alcohol-related disorders are primarily cross-sectional and compare intelligence test scores of individuals with and without alcohol-related disorders, hence mixing the influence of alcohol-related disorders and predisposing factors such as premorbid intelligence. In this large-scale study, the primary aim was to estimate associations of alcohol-related disorders with changes in intelligence test scores from early adulthood to late midlife. METHODS: Data were drawn from a follow-up study on middle-aged men, which included a re-examination of the same intelligence test as completed in young adulthood at military conscription (total analytic sample = 2,499). Alcohol-related hospital diagnoses were obtained from national health registries, whereas treatment for alcohol problems was self-reported at follow-up. The analyses included adjustment for year of birth, retest interval, baseline intelligence quotient (IQ) score, education, smoking, alcohol consumption, and psychiatric and somatic comorbidity. RESULTS: Individuals with alcohol-related hospital diagnoses (8%) had a significantly lower baseline IQ score (95.0 vs. 100.5, p < 0.001) and a larger decline in IQ scores from baseline to follow-up (-8.5 vs. -4.8, p < 0.001) than individuals without such diagnoses. The larger decline in IQ scores with alcohol-related hospital diagnoses remained statistically significant after adjustment for all the covariates. Similar results were revealed when IQ scores before and after self-reported treatment for alcohol problems (10%) were examined. CONCLUSIONS: Individuals with alcohol-related disorders have a lower intelligence test score both in young adulthood and in late midlife, and these disorders, moreover, seem to be associated with more age-related decline in intelligence test scores. Thus, low mean intellectual ability observed in individuals with alcohol-related disorders is probably a result of both lower premorbid intelligence and more intellectual decline.

Adult-Life Alcohol Consumption and Age-Related Cognitive Decline from Early Adulthood to Late Midlife.

AIMS: Alcohol consumption is a modifiable and plausible risk factor for age-related cognitive decline but more longitudinal studies investigating the association are needed. Our aims were to estimate associations of adult-life alcohol consumption and consumption patterns with age-related cognitive decline. METHODS: We investigated the associations of self-reported adult-life weekly alcohol consumption and weekly extreme binge drinking (≥10 units on the same occasion) with changes in test scores on an identical validated test of intelligence completed in early adulthood and late midlife in 2498 Danish men from the Lifestyle and Cognition Follow-up study 2015. Analyses were adjusted for year of birth, retest interval, baseline IQ, education and smoking. RESULTS: Men with adult-life alcohol consumption of more than 28 units/week had a larger decline in IQ scores from early adulthood to late midlife than men consuming 1-14 units/week (B29-35units/week = -3.6; P < 0.001). Likewise, a 1-year increase in weekly extreme binge drinking was associated with a 0.12-point decline in IQ scores (P < 0.001). Weekly extreme binge drinking explained more variance in IQ changes than average weekly consumption. In analyses including mutual adjustment of weekly extreme binge drinking and average weekly alcohol consumption, the estimated IQ decline associated with extreme binge drinking was largely unaffected, whereas the association with weekly alcohol consumption became non-significant. CONCLUSIONS: Adult-life heavy alcohol consumption and extreme binge drinking appear to be associated with larger cognitive decline in men. Moreover, extreme binge drinking may be more important than weekly alcohol consumption in relation to cognitive decline.

Social inequality in tooth loss, the mediating role of smoking and alcohol consumption.

OBJECTIVES: The objective of the study was to investigate the mediated proportion of smoking and alcohol consumption in the association between education and tooth loss. Further, the objective was, on the additive scale, to decompose the total effect of education on tooth loss into the direct effect of education, the natural indirect effect through smoking and alcohol consumption (differential exposure) and the mediated interaction between education, smoking and alcohol consumption on tooth loss (differential susceptibility). METHODS: The study was based on data from the Social Inequality in Cancer Cohort (SIC); a cohort constructed by seven pooled cohorts. The total study population comprised of 34 975 participants. With the use of natural effects models, we regarded smoking and alcohol consumption as intermediates; we investigated the role of smoking and alcohol consumption in mediating the effect of education on tooth loss. RESULTS: In total, 4924 participants had tooth loss defined as <15 teeth present. The results of the analyses, on the additive scale, showed 1202 (95% CI: 623-1781) additional persons with tooth loss per 10 000 persons among low compared to highly educated men. Among women, the analyses showed 1159 (95% CI: 959-1359) additional persons with tooth loss per 10 000 persons. The results, on the relative scale, showed that 11% (95% CI: 8%-15%) of the social inequality in tooth loss was jointly mediated by smoking and alcohol consumption among low-educated men. Among women with low education, the mediated proportion was 26% (95% CI: 19%-36%). CONCLUSION: Social inequality in tooth loss seems partly explained by differential exposure and differential susceptibility to smoking and alcohol consumption.

Does smoking during pregnancy mediate educational disparities in preterm delivery? Findings from three large birth cohorts.

BACKGROUND: Socio-economic disparities in preterm delivery have often been attributed to socially patterned smoking habits. However, most existing studies have used methods that potentially give biased estimates of the mediating effect of smoking. We used a contemporary mediation approach to study to which extent smoking during pregnancy mediates educational disparities in preterm delivery. METHODS: We performed a comparative analysis of data from three large birth cohort studies: the Danish National Birth Cohort (DNBC), the Dutch Generation R Study, and the Norwegian Mother and Child Cohort Study (MoBa). Risk of preterm delivery by maternal education is reported as risk differences and decomposed into a part explained by smoking and a part explained by other pathways. RESULTS: Proportions of preterm singleton deliveries were 4.8%-4.9% in all three cohorts. Total effects of maternal education were 2.0 (95% confidence interval [CI] 1.4, 2.5), 3.2 (95% CI 0.8, 5.2) and 2.0 (95% CI 0.9, 3.0) excess preterm deliveries per 100 singleton deliveries in DNBC, Generation R and MoBa when comparing primary/lower secondary education to an academic degree or equivalent. Smoking mediated, respectively, 22%, 10% and 19% of the excess risk in the DNBC, Generation R and MoBa cohorts. Adjustment for potential misclassification of smoking only increased mediated proportions slightly. CONCLUSIONS: Smoking during pregnancy explains part of educational disparities in preterm delivery, but the mediated proportion depends on the educational gradient in smoking, emphasising that educational disparities in preterm birth may be mediated by different risk factors in different countries.

Risk of adhesive bowel obstruction after abdominal surgery. A national cohort study of 665,423 Danish women.

BACKGROUND: Adhesive bowel obstruction is associated with considerable morbidity and mortality, but the magnitude of the risk is debated. METHOD: In a national cohort of all Danish women with an abdominal operation (N = 665,423) between 1977 and 2013, the risk of adhesive bowel obstruction was assessed by Cox multiple regression. Covariates were the number of abdominal operations, the surgical methods, the anatomical site involved, and the calendar year. RESULTS: In the cohort, 1.4% experienced an episode of adhesive bowel obstruction. The risk increased 33-43% during the study period, was lower after gynecological and obstetrical procedures compared to gastrointestinal (HR 0.36 [0.34-0.38]), lower after laparoscopic compared to laparotomic surgery (HR 0.51 [0.48-0.54]) and increased proportionally after each additional operation. CONCLUSIONS: The risk of adhesive bowel obstruction after abdominal operations depends on the site of earlier operations, the method of access and the number of earlier operations.

Job-exposure matrices addressing lifestyle to be applied in register-based occupational health studies.

OBJECTIVES: Information about lifestyle factors in register-based occupational health studies is often not available. The objective of this study was therefore to develop gender, age and calendar-time specific job-exposure matrices (JEMs) addressing five selected lifestyle characteristics across job groups as a tool for lifestyle adjustment in register-based studies. METHODS: We combined and harmonised questionnaire and interview data on lifestyle from several Danish surveys in the time period 1981-2013 for 264 054 employees registered with a DISCO-88 code (the Danish version of International Standard Classification of Occupations (ISCO)-88) in a nationwide register-based Danish Occupational Cohort. We modelled the probability of specified lifestyles in mixed models for each level of the four-digit DISCO code with age and sex as fixed effects and assessed variation in terms of intraclass correlation coefficients (ICCs) and exposure-level percentile ratios across jobs for six different time periods from 1981 through 2013. RESULTS: The ICCs were overall low (0.26%-7.05%) as the within-job group variation was large relative to the between job group variation, but across jobs the calendar period-specific ratios between highest and lowest predicted levels were ranging from 1.2 to 6.9, and for the 95%/1% and the 75%/5% percentile ratios ranges were 1.1-2.8 and 1.1-1.6, respectively, thus indicating substantial contrast for some lifestyle exposures and some occupations. CONCLUSIONS: The lifestyle JEMs may prove a useful tool for control of lifestyle-related confounding in register-based occupational health studies where lacking information on individual lifestyle factors may compromise internal validity.

Prospective Associations of the Short Form Health Survey Vitality Scale and Changes in Body Mass Index and Obesity Status.

Objectives: The objectives of the current study were to prospectively investigate the predictive value of the vitality scale of the Short Form Health Survey for changes in body mass index and development of obesity. Methods: The study population comprised 2864 (81.5%) men and 648 (18.5%) women from the Metropolit Project and the Danish Longitudinal Study on Work, Unemployment and Health, who participated in a follow-up examination in 2009-2011 corresponding to a follow-up period of 3-7 years. Associations of vitality with body mass index and obesity were investigated separately for men and women in linear and logistic regression models adjusting for age, baseline body mass index, education, physical activity, smoking, and obesity-related diseases. Results: Vitality was significantly associated with change in body mass index among men (p < 0.001) and women (p < 0.05) gaining weight after adjusting for age, baseline body mass index, education, physical activity, smoking, and obesity-related diseases. No significant associations of vitality with BMI change were observed among individuals maintaining or losing weight during the follow-up period. Furthermore, vitality significantly predicted development of obesity among women. Conclusion: The study indicates that vitality is of predictive value for increases in BMI over time among individuals gaining weight and may further predict the development of obesity among women. This identification of poor vitality as a potential risk indicator for weight gain and development of obesity may be beneficial in clinical practice.

Influence of socioeconomic factors and region of residence on cancer stage of malignant melanoma: a Danish nationwide population-based study.

BACKGROUND: Socioeconomic differences in survival after melanoma may be due to late diagnosis of the disadvantaged patients. The aim of the study was to examine the association between educational level, disposable income, cohabitating status and region of residence with stage at diagnosis of melanoma, including adjustment for comorbidity and tumor type. METHODS: From The Danish Melanoma Database, we identified 10,158 patients diagnosed with their first invasive melanoma during 2008-2014 and obtained information on stage, localization, histology, thickness and ulceration. Sociodemographic information was retrieved from registers of Statistics Denmark and data on comorbidity from the Danish National Patient Registry. We used logistic regression to analyze the associations between sociodemographic factors and cancer stage. RESULTS: Shorter education, lower income, living without partner, older age and being male were associated with increased odds ratios for advanced stage of melanoma at time of diagnosis even after adjustment for comorbidity and tumor type. Residence in the Zealand, Central and Northern region was also associated with advanced cancer stage. CONCLUSION: Socioeconomically disadvantaged patients and patients with residence in three of five health care regions were more often diagnosed with advanced melanoma. Initiatives to increase early detection should be directed at disadvantaged groups, and efforts to improve early diagnosis of nodular melanomas during increased awareness of the Elevated, Firm and Growing nodule rule and "when in doubt, cut it out" should be implemented. Further studies should investigate regional differences in delay, effects of number of specialized doctors per inhabitant as well as differences in referral patterns from primary to secondary health care across health care regions.

Change in weight status from childhood to early adulthood and late adulthood risk of colon cancer in men: a population-based cohort study.

BACKGROUND: Although weight gain in mid- to late adult life is associated with an increased risk of colon cancer, it is unclear if increases or losses in weight from childhood to early adulthood are differentially associated with risks of adult colon cancer. METHODS: Weight and height were measured at 7 or 13 years and in early adulthood (17-26 years) in 64,675 boys in the Copenhagen School Health Records Register and the Danish Conscription Database. Cases of colon cancer (n = 751) were identified in the Danish Cancer Registry. Boys and young men were categorized as normal weight or overweight. Associations between changes in weight and colon cancer were examined using Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with men with a normal weight at 7 years and in early adulthood, men with overweight at both ages had an increased risk of adult colon cancer (HR: 2.73, 95% CI 1.80-4.15). In contrast, men with overweight at 7 years, but not in early adulthood did not have an increased risk of colon cancer (HR: 0.73, 95% CI 0.35-1.54), nor did men with a normal weight at 7 years and overweight in early adulthood (HR: 1.28, 95% CI 0.96-1.70). Similar results were observed for weight status at age 13 years combined with early adulthood. CONCLUSIONS: Childhood overweight that persists into early adulthood is associated with an increased risk of colon cancer, whereas overweight that disappears before early adulthood or developed after childhood is not.

Is male factor infertility associated with midlife low-grade inflammation? A population based study.

Male factor infertility is associated with an increased risk of disease and mortality, which has been related to markers of chronic systemic inflammation. The objective of this study was to investigate the association between male factor infertility and low-grade inflammation and furthermore to examine the lifetime prevalence of male factor infertility and overall infertility (also including female and couple infertility). The study population consisted of 2140 members of the Metropolit 1953 Danish Male Birth Cohort who had participated in the Copenhagen Aging and Midlife Biobank data collection in 2009-2011. Information on male factor infertility and overall infertility was obtained from a questionnaire, and low-grade inflammation was evaluated as the highest plasma levels of C-reactive protein, interleukin-6 and tumour necrosis factor-alpha in the population. The level of interleukin-6 was significantly higher among men with male factor infertility compared with other men adjusted for potential confounders. This was not found for the two other inflammatory markers. The lifetime prevalence of male factor infertility and overall infertility were 10.2% and 17.9%, respectively. The findings suggest that male factor infertility might be associated with an increased level of interleukin-6.

Cognitive Change during the Life Course and Leukocyte Telomere Length in Late Middle-Aged Men.

Importance: Cognitive skills are known to decline through the lifespan with large individual differences. The molecular mechanisms for this decline are incompletely understood. Although leukocyte telomere length provides an index of cellular age that predicts the incidence of age-related diseases, it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life style. Design, Setting, and Participants: Two groups of men with negative (n = 97) and positive (n = 93) change in cognitive performance were selected from a birth cohort of 1985 Danish men born in 1953. Cognitive performance of each individual was assessed at age ~20 and 56 years. Leukocyte telomere length at age ~58 was measured using qPCR. Linear regression models were used to investigate the association between cognitive function and leukocyte telomere length. Results: Men with negative change in cognitive performance during adult life had significantly shorter mean leukocyte telomere length than men with positive change in cognitive performance (unadjusted difference ß = -0.09, 95% CI -0.16 to -0.02, p = 0.02). This association remained significant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index (BMI) and cholesterol (adjusted difference ß = -0.09, 95% CI -0.17 to -0.01, p = 0.02) but was non-significant after adjusting for smoking, alcohol consumption, leisure time activity, BMI, cholesterol, current cognitive function, depression and education (adjusted difference ß = -0.07, 95% CI -0.16 to -0.01, p = 0.08). Conclusion and Relevance: Preclinical cognitive changes may be associated with leukocyte telomere length.