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Objective The study aims to identify the mediating factors of the relationship between education achievement and incident type 2 diabetes mellitus (T2DM) in older adults. Design Population-based cohort study. Setting Participants were recruited from the German federal state of Saarland. Participants Participants were excluded if they had prevalent T2DM or missing data on prevalent T2DM, missing or zero follow-up time for incident T2DM or were under 50 years of age. The total sample consisted of 7462 individuals aged 50-75 years (42.8% men, mean age 61.7 years) at baseline (2000-02). The median follow-up time was 8.0 years. Methods Cox proportional hazards regression was initially used to determine the direct association between education achievement and incident T2DM. Using the Baron and Kenny approach, we then investigated the associations between education achievement and incident T2DM with the potential mediators. The contribution of each of the putative mediating variables was then calculated. Results A clear socioeconomic gradient was observed with regard to T2DM incidence with the lowest educated individuals at a greater risk of developing the disease during the follow-up period: HR (95% CI) high education: 0.52 (0.34 to 0.80); medium education: 0.80 (0.66 to 0.96). Seven of the variables considered explained a proportion of the education-T2DM relationship (body mass index, alcohol consumption, hypertension, fasting triglycerides, high-density lipoprotein (HDL) cholesterol, physical activity and smoking status), where the contribution of the variables ranged from 1.0% to 17.7%. Overall, the mediators explained 31.7% of the relationship. Conclusion By identifying the possible mediating factors of the relationship between education achievement and incident T2DM in older adults, the results of this study can be used to assist with the development of public health strategies that aim to reduce socioeconomic inequalities in T2DM. [ABSTRACT FROM AUTHOR]

Background Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Methods Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Results Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. Conclusions We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by differences in comorbidity. Future studies on DMPs should consider contextual effects when analysing programme effectiveness or impacts on equity and efficiency. [ABSTRACT FROM AUTHOR]

Objective To study the association of self-reported physical activity level with prognosis in a cohort of patients with coronary heart disease (CHD), with a special focus on the dose-response relationship with different levels of physical activity. Methods Data were drawn from a prospective cohort of 1038 subjects with stable CHD in which frequency of strenuous leisure time physical activity was assessed repeatedly over 10 years of follow-up. Multiple Cox proportional hazards regression models were used to assess the association of physical activity level with different outcomes of prognosis (major cardiovascular events, cardiovascular mortality, all-cause mortality), with different sets of adjustments for potential confounders and taking into account time-dependence of frequency of physical activity. Results A decline in engagement in physical activity over follow-up was observed. For all outcomes, the highest hazards were consistently found in the least active patient group, with a roughly twofold risk for major cardiovascular events and a roughly fourfold risk for both cardiovascular and all-cause mortality in comparison to the reference group of moderately frequent active patients. Furthermore, when taking time-dependence of physical activity into account, our data indicated reverse J-shaped associations of physical activity level with cardiovascular mortality, with the most frequently active patients also having increased hazards (2.36, 95% CI 1.05 to 5.34). Conclusions This study substantiated previous findings on the increased risks for adverse outcomes in physically inactive CHD patients. In addition, we also found evidence of increased cardiovascular mortality in patients with daily strenuous physical activity, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Background and aims Standard epidemiological measures of the risk of premature death from smoking might be unsuitable for risk communication in actual counselling situations. The rate advancement period (RAP) is an epidemiologic metric that could be useful for conveying information on the benefits of quitting. More effective risk communication could motivate older smokers to make an attempt at quitting. We provide empirical evidence on the impact of smoking, and the benefits of quitting on all-cause mortality and RAPs for people aged 60 years and older in a large cohort of older adults. Methods Smoking information was obtained from 6545 participants aged 60–74 years of ESTHER, a population-based German cohort. Cox proportional hazards regression was applied to estimate associations of smoking status, amount of smoking and time since smoking cessation with all-cause mortality. Premature mortality was quantified by RAPs. Results Current smokers had a 2.5-fold increased risk for all-cause mortality (adjusted HR: 2.53, 95% CI 2.10 to 3.03) and an RAP of 10.7 years when compared with never smokers. Strong dose-response relationships were seen with both current and life-time amount of smoking. Compared with current smokers, significant mortality reductions by 30%, 39% and 59%, and rate advancement reductions of 4.0, 5.6 and 10.0 years within <10 years, 10– 19 years and ≥20 years after cessation were found for former smokers, respectively. Conclusions Smoking remains a strong risk factor for premature mortality, and smoking cessation remains highly beneficial also at older ages. [ABSTRACT FROM AUTHOR]

Objective Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. Design Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39 266) and in combination with gender, age and FH (n=11 324). Model discriminatory performance was assessed using 10-fold internal crossvalidation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and genderspecific population risks. Results The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2×10-16), confirmed in external validation sets (Sweden p=1.2×10-6, Finland p=2×10-5). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Conclusion Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance. [ABSTRACT FROM AUTHOR]

Objectives To measure changes in prevalence and predictors of home smoking bans (HSBs) among smokers in four European countries after the implementation of national smoke-free legislation. Design Two waves of the International Tobacco Control Policy Evaluation Project Europe Surveys, which is a prospective panel study. Pre- and post-legislation data were used from Ireland, France, Germany and the Netherlands. Two pre-legislation waves from the UK were used as control. Participants 4634 respondents from the intervention countries and 1080 from the control country completed both baseline and follow-up and were included in the present analyses. Methods Multiple logistic regression models to identify predictors of having or of adopting a total HSB, and Generalised Estimating Equation models to compare patterns of change after implementation of smoke-free legislation to a control country without such legislation. Results Most smokers had at least partial smoking restrictions in their home, but the proportions varied significantly between countries. After implementation of national smoke-free legislation, the proportion of smokers with a total HSB increased significantly in all four countries. Among continuing smokers, the number of cigarettes smoked per day either remained stable or decreased significantly. Multiple logistic regression models indicated that having a young child in the household and supporting smoking bans in bars were important correlates of having a pre-legislation HSB. Prospective predictors of imposing a HSB between survey waves were planning to quit smoking, supporting a total smoking ban in bars and the birth of a child. Generalised Estimating Equation models indicated that the change in total HSB in the intervention countries was greater than that in the control country. Conclusions The findings suggest that smoke-free legislation does not lead to more smoking in smokers' homes. On the contrary, our findings demonstrate that smoke-free legislation may stimulate smokers to establish total smoking bans in their homes. [ABSTRACT FROM AUTHOR]

Objective The risk of colorectal cancer after a previous negative colonoscopy is very low. Nevertheless, interval cancers occur. We aimed to assess the characteristics and predictors of interval cancers after negative colonoscopy. Methods A population-based case-control study was conducted in Southern Germany in 2003e7. Sociodemographic and tumour characteristics were compared among 78 patients with interval cancers occurring 1e10 years after a negative colonoscopy and 433 colorectal cancers detected at screening. In addition, the indication for the preceding negative colonoscopy and its completeness were compared between patients with interval cancers and 515 controls with a preceding negative colonoscopy. Results 56.4% of interval cancers occurred among women compared with 33.7% of cases detected by screening (p=0.0001). After adjustment for covariates, female sex (OR 2.28, 95% CI 1.35 to 3.83) and location in the caecum or ascending colon (OR 1.98, 95% CI 1.17 to 3.35) were independently associated with occurrence of interval cancers. The preceding negative colonoscopy was more commonly conducted because of a positive faecal occult blood test (26.0% vs 12.9%, p¼0.009) and was more often incomplete (caecum not reached: 18.1% vs 6.7%, p=0.001) among interval cancer cases than among controls. Characteristics of the preceding negative colonoscopy strongly and independently associated with occurrence of interval cancers were follow-up of a positive faecal occult blood test among men (OR 5.49, 95% CI 2.10 to 14.35) and incompleteness among women (OR 4.38, 95% CI 1.69 to 11.30). Conclusions The observed patterns suggest that a substantial proportion of interval cancers are due to neoplasms missed at colonoscopy and are potentially preventable by enhanced performance of colonoscopy. [ABSTRACT FROM AUTHOR]

Objective High serum calcium and phosphate levels have been linked to cardiovascular diseases and all-cause mortality but evidence from longitudinal studies is scarce, especially among patients with pre-existing coronary heart disease. The association between baseline calcium and phosphate and prognosis was examined in a cohort study of patients with stable coronary heart disease. Methods Serum calcium and phosphate were measured in a cohort of initially 1206 patients undergoing a 3 week rehabilitation programme after an acute cardiovascular event and subsequently being followed-up for 8 years. Multivariate Cox regression was employed to assess the association of quartiles and continuous levels of calcium and phosphate with secondary cardiovascular events and all-cause mortality. Results No significant risk elevations were observed for secondary cardiovascular event incidence in models adjusted for a variety of potential confounders. High calcium levels, however, were strongly associated with mortality risk in adjusted models (HRQ4vsQ1=2.39 (1.22 to 4.66)). In additional multivariable analyses, the calcium/albumin ratio was predictive for all-cause mortality (HRQ4vsQ1=2.66 (1.35 to 5.22)) and marginally predictive for cardiovascular event incidence (HRQ4vsQ1=1.74 (1.00 to 3.05)). Conclusions Calcium and the ratio of calcium with albumin, its major binding protein, were strongly associated with all-cause mortality among patients with coronary heart disease. The underlying mechanisms and the clinical implications of these findings deserve further study. [ABSTRACT FROM AUTHOR]

Background and objective Recent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a highrisk population with stable coronary heart disease. Methods Based on measurements of PTH levels in 1133 patients recruited at two German rehabilitation clinics and followed over 8 years, multivariate Cox regression analysis was performed to estimate the risk of secondary cardiovascular events (including myocardial infarction, stroke and death due to cardiovascular diseases) and allcause- mortality according to PTH quartiles (Q1eQ4) and continuous PTH concentrations. Results During follow-up, 153 cardiovascular events and 124 deaths occurred. Age and sex-adjusted Cox regression analysis yielded statistically significant positive associations of PTH with both cardiovascular event incidence and all-cause mortality (HR (95% CI) per SD increase of PTH: 1.35 (1.21e1.51) and 1.25 (1.11e1.42), respectively). Associations remained essentially unchanged after additional adjustment for multiple cardiovascular risk factors. More detailed doseeresponse analyses showed strong risk elevation for above-normal levels of PTH (>95th percentile), with essentially no association at lower levels. Conclusion The results of this first detailed study in a cohort of patients with stable coronary heart disease suggest an independent predictive value of above-normal PTH for the prognosis in patients with stable coronary heart disease. [ABSTRACT FROM AUTHOR]

Objectives Although smoking causes a variety of diseases and both, a high smoking prevalence and permanent occupational disability are a great burden on the population level, data about the impact of smoking habits on occupational disability are sparse. The objective of this study was to examine the influence of smoking habits on occupational disability among construction workers, an occupational group with particularly high smoking prevalence. Methods The association between smoking and occupational disability was examined during a mean follow-up of 10.8 years in a cohort of 14 483 male construction workers in Württemberg, Germany. The cohort was linked to the regional pension register of the German pension fund to identify workers who were granted a disability pension during the follow-up. HRs (Hazard Ratios) were calculated with non-smokers as reference by the Cox proportional hazards model adjusting for potential confounding factors such as age, nationality, type of occupation, alcohol consumption and body mass index. Results Overall, 2643 cases of occupational disability were observed, with dorsopathy (21%) being the most common cause. Clear dose-response relationships were seen between smoking and occupational disability due to all causes, as well as occupational disability due to respiratory, cardiovascular and mental diseases, cancer and dorsopathy. Particularly strong associations were seen between heavy smoking (≥20 cigarettes/day) and occupational disability due to mental and respiratory diseases (HR 3.25, 95% CI 1.93 to 5.46 and HR 3.26, 95% CI 1.69 to 6.27, respectively). Conclusion Smoking is associated with increased risk of occupational disability among construction workers, in particular occupational disability due to respiratory, cardiovascular and mental diseases, cancer and dorsopathy. [ABSTRACT FROM AUTHOR]

Objectives: To derive age and sex specific estimates of transition rates from advanced adenomas to colorectal cancer by combining data of a nationwide screening colonoscopy registry and national data on colorectal cancer (CRC) incidence. Design: Registry based study. Setting: National screening colonoscopy programme in Germany. Patients: Participants of screening colonoscopy in 2003 and 2004 (n = 840 149). Main outcome measures: Advanced adenoma prevalence, colorectal cancer incidence, annual and 10 year cumulative risk of developing CRC among carriers of advanced adenomas according to sex and age (range 55-80+ years) Results: The age gradient is much stronger for CRC incidence than for advanced adenoma prevalence. As a result, projected annual transition rates from advanced adenomas to CRC strongly increase with age (from 2.6% in age group 55-59 years to 5.6% in age group ⩾80 years among women, and from 2.6% in age group 55-59 years to 5.1% in age group ⩾80 years among men). Projections of 10 year cumulative risk increase from 25.4% at age 55 years to 42.9% at age 80 years in women, and from 25.2% at age 55 years to 39.7% at age 80 years in men. Conclusions: Advanced adenoma transition rates are similar in both sexes, but there is a strong age gradient for both sexes. Our estimates of transition rates in older age groups are in line with previous estimates derived from small case series in the pre-colonoscopy era independent of age. However, our projections for younger age groups are considerably lower. These findings may have important implications for the design of CRC screening programmes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate new strategies to enhance the promotion of smoking cessation in general practice. Design: Cluster randomised trial, 2x2 factorial design. Setting: 82 medical practices in Germany, including 94 general practitioners. Participants: 577 patients who smoked at least 10 cigarettes per day (irrespective of their intention to stop smoking) and were aged 36-75 years. Interventions: Provision of a 2-h physician group training in smoking cessation methods and direct physician payments for every participant not smoking 12 months after recruitment (TI, training+incentive); provision of the same training and direct participant reimbursements for pharmacy costs associated with nicotine replacement therapy or bupropion treatment (TM, training+medication). Main outcome measure: Self-reported smoking abstinence obtained at 12 months follow-up and validated by serum cotinine. Results: In intention-to-treat analysis, smoking abstinence at 12 months follow-up was 3% (2/74), 3% (5/144), 12% (17/140) and 15% (32/219) in the usual care, and interventions TI, TM and TI+TM, respectively. Applying a mixed logistic regression model, no effect was identified for intervention TI (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.65 to 2.43), but intervention TM strongly increased the odds of cessation (OR 4.77, 95% CI 2.03 to 11.22). Conclusion: Providing cost-free effective drugs to patients along with improved training opportunities for general practitioners could be an effective measure to achieve successful promotion of smoking cessation in general practice. [ABSTRACT FROM AUTHOR]

Objectives: It has been suggested that hormone replacement therapy (HRT) may protect against osteoarthritis (OA). The aim of this paper was to assess the association between HRT and radiographically defined patterns of OA.Methods: 475 consecutive women aged 50 years or older (mean age 66.1) who underwent hip or knee joint replacement because of advanced OA in four hospitals in south west Germany were enrolled in a cross sectional study. Participants underwent a standardised interview including detailed history of medication use and a physical examination. Furthermore, radiographs of the joint being replaced and of the contralateral joint as well as of both hands were obtained. Patients were categorised as having bilateral or unilateral OA according to the presence or absence of radiographic OA in the contralateral joint. If radiographic OA of different hand and finger joint groups was present, participants were categorised as having generalised OA (GOA). Logistic regression was used to estimate odds ratios and their 95% confidence intervals for the association between HRT and bilateral or GOA while adjusting for potential confounders.Results: Fifty five women (11.6%) were using HRT. The median duration of use was 5.4 years. The prevalence of bilateral and GOA was similar among users of ORT (86.3% and 27.5%, respectively) and among non-users of HRT (88.7% and 35.7%, respectively). After adjustment for potential confounding factors, the odds ratios (95% confidence intervals) of bilateral OA and GOA among HRT users compared with non-users was 1.21 (0.48, 3.03) and 1. 21 (0.53, 2.74), respectively.Conclusion: Despite limited generalisability because of the selective study sample, these data do not support the hypothesis that HRT acts as a systemic protective factor against OA. [ABSTRACT FROM AUTHOR]

Assesses the relation of smoking and alcohol and coffee consumption to active Helicobacter pylori infection. Prevalence of H. pylori; Determining the active infection with H. pylori; Results of the study.

The article presents a study on the impact of screening sigmoidoscopy and colonoscopy on the incidence of and mortality from colorectal cancer. It discusses the decline in incidence and mortality by screening sigmoidoscopy and screening colonoscopy, and the underestimation of the effects of sigmoidoscopy in randomized controlled studies.

Background Dichotomisation of continuous variables before analysis has frequently been criticised but, nonetheless, remains a common approach. We were interested in the effects of dichotomisation of an outcome variable when two predictors are examined. Methods Assuming a log-normally distributed continuous outcome, a three-level and a binary independent variable, we evaluated the results that would be obtained by logistic regression after dichotomisation. Different cut-offs, predictor effects and dispersions were examined, with a special focus on interaction terms. Results Depending on the specific parameter combination, dichotomisation introduced sometimes substantial spurious interactions between the two predictor variables regarding their association with the outcome. These interactions could be assigned statistical significance even with modest sample sizes. Real-life data on sex-weight as determinants of γ?-glutamyltransferase provided a practical example of these issues. Conclusions The findings presented add a new aspect to the controversy surrounding dichotomisation of continuous variables. Researchers should critically examine whether the validity of their results might be hampered by such phenomena. [ABSTRACT FROM AUTHOR]

Assesses the relationship between parental history of gastric or duodenal ulcer and infection with Helicobacter pylori in preschool children. Subjects and methodology of the study; Results of the study; Comment of the author on the study.

Objectives: Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics., Methods: We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n snps =5) or sedentary time (n snps =6), or accelerometer-measured (n snps =1) or self-reported (n snps =5) vigorous physical activity., Results: Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;~8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (~7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger)., Conclusion: Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women., Competing Interests: Competing interests: MWB conducts research funded by Amgen, Novartis and Pfizer. PAF conducts research funded by Amgen, Novartis and Pfizer. He received honoraria from Roche, Novartis and Pfizer. AWK declares research funding to her institution from Myriad Genetics for an unrelated project (funding dates 2017-2019). SL declares grants and honoraria paid to her institution from Amgen, Novartis, Pfizer, Roche, and, outside the submitted work, grants and/or honoraria paid to her institution from AbbVie, Celgene, Seattle Genetics, PrIME/Medscape, Daiichi-Sankyo, Lilly, Samsung, BMS, Puma, Immunomedics, AstraZeneca, Pierre Fabre, Merck, GlaxoSmithKlein, EirGenix, and Bayer, and personal fees from Chugai; SL also has a patent EP14153692.0 pending. UM declares stock ownership in Abcodia Ltd. RAM has been a consultant for Pharmavite. No other authors have conflicts to declare., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)