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Objectives: To investigate gender‐specific factors associated with case complexity in a population‐based sample of middle‐aged and older adults using a holistic approach to complexity. Methods: Data were derived from the 8‐year follow‐up home visits of the ESTHER study—a German population‐based study in middle‐aged and older adults. Cross‐sectional analyses were conducted for 2932 persons (aged 57–84). Complexity was assessed by the well‐established INTERMED for the elderly interview, which uses a holistic approach to the definition of case complexity. The association between various bio‐psycho‐social variables and case complexity was analyzed using gender‐specific logistic regression models, adjusted for sociodemographic factors (age, marital status, education). Results: Prevalence of complexity was 8.3% with significantly higher prevalence in female (10.6%) compared to male (5.8%) participants (p < 0.001). Variables associated with increased odds for complexity in both, women and men were: being divorced (odds ratio [OR] women: 1.86, 95% CI 1.05–3.30; OR men: 3.19, 1.25–8.12), higher total somatic morbidity (women: 1.08, 1.04–1.12; men: 1.06, 1.02–1.11), higher depression severity (women: 1.34, 1.28–1.40; men: 1.35, 1.27–1.44), and higher loneliness scores (women: 1.19, 1.05–1.36; men: 1.23, 1.03–1.47). Women (but not men) with obesity (Body mass index [BMI] ≥30) had higher odds (1.79, 1.11–2.89) for being complex compared to those with a BMI <25. High oxidative stress measured by derivatives of reactive oxygen metabolites in serum was associated with 2.02 (1.09–3.74) higher odds for complexity only in men. Conclusions: This study provides epidemiological evidence on gender differences in prevalence and factors associated with case complexity in middle‐aged and older adults. Moreover, this study adds to the holistic understanding of complexity by identifying novel variables linked to complexity among middle‐aged and older individuals. These factors include loneliness for both genders, and high oxidative stress for men. These findings should be confirmed in future longitudinal studies. Key points: Prevalence of complexity was found to be 8.3% with significantly higher prevalence in women (10.6%) compared to men (5.8%) (p < 0.001).Being divorced, higher total somatic morbidity, higher depression severity, and higher loneliness scores were associated with higher odds for complexity in both genders.Obesity was linked to higher odds for complexity only in women, while high oxidative stress was linked to complexity only in men.This study expands the holistic understanding of complexity by identifying novel variables associated with complexity in middle‐aged and older adults, including loneliness for both genders and high oxidative stress for men. [ABSTRACT FROM AUTHOR]

Simple Summary: After getting treated for colorectal cancer, many people feel fatigue, stress, and pain and face other challenges that can make daily activities and work tough. Our research explored how these issues group together and if they are connected to fatigue and difficulties in work. We gathered data from the MIRANDA study, where patients shared their experiences after colorectal cancer treatment before the start of the rehabilitation and three months after. Using data from their questionnaire responses, we identified six main problem groups: fatigue, digestive troubles, pain, feelings of stress or anxiety, urinary issues, and side effects from chemotherapy. Our findings reveal that experiencing even a single symptom from these categories can be a precursor to feeling more fatigued or having a decreased ability to work. Our findings shed light on colorectal cancer survivors' various challenges and how they might impact their daily lives and work. In colorectal cancer (CRC) patients, apart from fatigue, psychological and physical symptoms often converge, affecting their quality of life and ability to work. Our objective was to ascertain symptom clusters within a year following CRC treatment and their longitudinal association with persistent fatigue and reduced work ability at the 3-month follow-up. We used data from MIRANDA, a multicenter cohort study enrolling adult CRC patients who are starting a 3-week in-patient rehabilitation within a year post-curative CRC treatment. Participants completed questionnaires evaluating symptoms at the start of rehabilitation (baseline) and after three months. We performed an exploratory factor analysis to analyze the clustering of symptoms at baseline. Longitudinal analysis was performed using a multivariable linear regression model with dichotomized symptoms at baseline as independent variables, and the change in fatigue and ability to work from baseline to 3-month-follow-up as separate outcomes, adjusted for covariates. We identified six symptom clusters: fatigue, gastrointestinal symptoms, pain, psychosocial symptoms, urinary symptoms, and chemotherapy side effects. At least one symptom from each factor was associated with higher fatigue or reduced ability to work at the 3-month follow-up. This study highlights the interplay of multiple symptoms in influencing fatigue and work ability among CRC patients post-rehabilitation. [ABSTRACT FROM AUTHOR]

We explored the relationship between benefit finding (BF)/posttraumatic growth (PTG) at baseline and health-related quality of life (HRQOL) at baseline and follow-up in long-term cancer survivors (LTCS; ≥5-year post-diagnosis). HRQOL was assessed in LTCS in 2009–2011 (5- to 16-year post-diagnosis, baseline) and re-assessed in 2018/2019 (14- to 24-year post-diagnosis, follow-up). BF and PTG were measured at baseline; mean scores were dichotomized into 'none-to-low' (<3) and 'moderate-to-high' (> =3). Linear regression models and linear mixed regression models were employed to assess the association of BF/PTG with HRQOL. Of the 6057 baseline participants, 4373 were alive in 2019, of whom 2704 completed the follow-up questionnaire. Cross-sectionally, LTCS with none-to-low BF reported better HRQOL at baseline and at follow-up than LTCS with higher BF. Longitudinally, no difference was found between none-to-low and moderate-to-high BF on the HRQOL change from baseline to follow-up. HRQOL differences between the PTG groups were not statistically significant cross-sectionally and longitudinally, except those participants with moderate-to-high PTG reported higher role functioning and global health status/QOL. Cross-sectionally, BF was significantly negatively related to subscales of HRQOL, while PTG was positively correlated to role functioning and global health status/QOL. The results add further evidence that BF and PTG are two different positive psychological concepts. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) patients often experience fatigue, poor ability to work, and low quality of life (QoL) after therapy. We conducted a prospective study of 147 CRC patients who underwent a three-week in-patient rehabilitation clinic visit in Germany. Patients completed questionnaires at the start of rehabilitation and at regular 3-month intervals for up to a year. We found a strong correlation between fatigue and QoL, and moderate correlations between fatigue and the ability to work, as well as between QoL and the ability to work. Fatigue, QoL, and ability to work improved significantly from the start of rehabilitation to the three-month follow-up, and there was little change afterward in the first year after rehabilitation. In summary, fatigue, QoL, and the ability to work were highly interconnected in CRC patients, and all of them improved from the start of rehabilitation to the 3-month follow-up. Cancer-related fatigue, low quality of life (QoL), and low ability to work are highly prevalent among colorectal cancer (CRC) patients after tumor surgery. We aimed to analyze their intercorrelations and trajectories in the first year after in-patient rehabilitation in the German multicenter MIRANDA cohort study. Recruitment is ongoing, and we included the first 147 CRC patients in this analysis. Participants filled out questionnaires at the beginning of in-patient rehabilitation (baseline) and at 3, 6, 9, and 12 months after the baseline. The EORTC-QLQ-C30-General-Health-Status (GHS)/QoL, the FACIT-F-Fatigue Scale, and the FACIT-F-FWB-ability-to-work items were used to evaluate QoL, fatigue, and ability to work, respectively. The fatigue and QoL scales were highly correlated (r = 0.606). A moderate correlation was observed between the fatigue and ability to work scales (r = 0.487) and between the QoL and ability to work scales (r = 0.455). Compared to the baseline, a statistically significant improvement in the QoL, ability to work, and fatigue scales were observed at the 3-month follow-up (Wilcoxson signed rank test, all p < 0.0001). The three scales plateaued afterward until the 12-month follow-up. In conclusion, fatigue, QoL, and ability to work were highly interrelated, improved quickly during/after in-patient rehabilitation, and did not change much afterward in German CRC patients. [ABSTRACT FROM AUTHOR]

Objective: We analyzed the pooled case‐control data from the International Head and Neck Cancer Epidemiology (INHANCE) consortium to compare cigarette smoking and alcohol consumption risk factors for head and neck cancer between less developed and more developed countries. Subjects and Methods: The location of each study was categorized as either a less developed or more developed country. We compared the risk of overall head and neck cancer and cancer of specific anatomic subsites associated with cigarette smoking and alcohol consumption. Additionally, age and sex distribution between categories was compared. Results: The odds ratios for head and neck cancer sites associated with smoking duration differed between less developed and more developed countries. Smoking greater than 20 years conferred a higher risk for oral cavity and laryngeal cancer in more developed countries, whereas the risk was greater for oropharynx and hypopharynx cancer in less developed countries. Alcohol consumed for more than 20 years conferred a higher risk for oropharynx, hypopharynx, and larynx cancer in less developed countries. The proportion of cases that were young (<45 years) or female differed by country type for some HNC subsites. Conclusion: These findings suggest the degree of industrialization and economic development affects the relationship between smoking and alcohol with head and neck cancer. [ABSTRACT FROM AUTHOR]

Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors. [ABSTRACT FROM AUTHOR]

Background: Evidence about the clinical relevance of appropriate comedication among older colorectal cancer (CRC) patients is sparse.Methods: A cohort study was conducted with 3239 CRC patients aged 65 years and older. To assess comedication quality, we calculated the total Fit fOR The Aged (FORTA) score and its subscores for medication overuse, underuse, and potentially inappropriate medication use. Multivariable Cox proportional hazards or logistic regression models were performed to evaluate the association of comedication quality with up to 5-year overall survival, CRC-specific survival, and chemotherapy-related adverse drug reactions.Results: Overall, 3239 and 1209 participants were included in analyses on survival and adverse drug reactions, respectively. The hazard ratios [95% confidence intervals] for the total FORTA score ≥ 7 versus 0-1 points were 1.83 [1.40-2.40] and 1.76 [1.22-2.52] for up to 5-year overall and CRC-specific survival, respectively. Worse up to 5-year overall survival and CRC-specific survival was also evident for FORTA subscores for potentially inappropriate medication use and overuse, whereas no association was observed for underuse. Although results for the total FORTA and potentially inappropriate medication score were much stronger among patients receiving chemotherapy, no significant associations with chemotherapy-related adverse drug reactions were observed. Moreover, associations were particularly strong among men and rectal cancer patients as compared to women and colon cancer patients.Conclusions: Poor total comedication quality was significantly associated with worse up to 5-year overall and CRC-specific survival. Randomized controlled trials are needed to test whether improved cancer comedication management in older CRC patients prolongs survival. [ABSTRACT FROM AUTHOR]

Background: The incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants.Methods: Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve.Results: Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores.Conclusions: Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes. [ABSTRACT FROM AUTHOR]

Background: Cancer studies reported mixed results on benefit finding (BF) and posttraumatic growth (PTG) prevalence and few were focused on long-term survivors.Methods: BF and PTG were assessed in a multi-regional population-based study in Germany with 6952 breast, colorectal and prostate cancer survivors, using the Benefit Finding Scale and Posttraumatic Growth Inventory. We calculated the age-adjusted prevalence, stratified by demographical and clinical characteristics.Results: Overall, 66.0% of cancer survivors indicated moderate-to-high BF, and 20.5% moderate-to-high PTG. Age-adjusted prevalence of BF and PTG differed according to cancer type (breast > colorectal > prostate) and sex (female > male). BF and PTG prevalence were higher in younger than in older respondents; the age-adjusted prevalence was higher in respondents who survived more years after diagnosis. The strength and direction of associations of age-adjusted prevalence with cancer stage, disease recurrence, and time since diagnosis varied according to cancer type and sex.Conclusions: A substantial proportion of long-term cancer survivors reported moderate-to-high BF and PTG. However, the prevalence was lower in older and male cancer survivors, and during the earlier years after cancer diagnosis. Further longitudinal studies on PTG and BF in cancer survivors are warranted to address heterogeneity in survivors' experience after cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity.Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis.Results: A total of 667,916 individuals were included with an overall median (P25-P75) age at recruitment of 62.3 (57-67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86-1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08-1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82-1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77-0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89-1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity.Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans. [ABSTRACT FROM AUTHOR]

Background: The question of whether having a family history of prostatic borderline or in situ neoplasia (PBISN) is associated with an increased risk of invasive prostate cancer (PCa) or death from PCa remains unanswered. The objective of the current study was to provide an evidence-based risk estimation for the relatives of patients with PBISN.Methods: Nationwide Swedish family cancer data sets were used for the current study, including data regarding all residents of Sweden who were born after 1931 and their parents. Standardized incidence ratios (SIRs), standardized mortality ratios (SMRs), and lifetime cumulative risks of PCa were calculated for men with different constellations of family history. Family history was defined as a dynamic (time-dependent) variable considering changes during follow-up (1958-2015).Results: Of the 6,343,727 men in the current study, a total of 238,961 developed invasive PCa and 5756 were diagnosed with PBISN during the follow-up. Men with 1 first-degree relative who was diagnosed with PBISN had a 70% increased risk of invasive PCa (SIR, 1.7; 95% confidence interval, 1.5-1.9) and PCa death (SMR, 1.7; 95% confidence interval, 1.3-2.2) compared with men with no family history of PBISN or invasive PCa. These were rather close to estimates in men with 1 first-degree relative diagnosed with invasive PCa (SIR, 2.1 and SMR, 1.8). A higher risk of PCa in family members was found among patients with a family history of PBISN and/or PCa diagnosed before age 60 years. The results in terms of cumulative risk resembled this trend.Conclusions: A family history of PBISN appears to be as important as a family history of invasive PCa with regard to an increased risk of invasive PCa or PCa mortality. Such a history should not be overlooked in PCa screening recommendations or in future research regarding familial PCa. [ABSTRACT FROM AUTHOR]

Background: Familial breast cancer risk studies usually overlook the dynamic nature of family history.Methods: The authors assessed the effect of incorporating the timing of cancer diagnosis events into the assessment of familial risks of breast cancer in first-degree and second-degree relatives in a nationwide cohort study of 5,099,172 women (follow-up was between 1958-2015). Family history was assessed using 3 approaches: 1) as a static variable (ever having a relative with breast cancer); 2) as accumulative history; and 3) as a dynamic variable (time-dependent variable).Results: For women aged <50 years, familial risk was mostly higher when family history was assessed as a dynamic variable compared with using a static or accumulative family history. For example, the cumulative risk of receiving a breast cancer diagnosis until age 50 years for women with a history of breast cancer in 1 first-degree relative was 2.6% (95% CI, 2.5%-2.7%) using the static method, 2.4% (95% CI, 2.3%-2.4%) using the accumulative method, and 3.1% (95% CI, 3.0%-3.2%) using the dynamic method. Relative risk in women aged <50 years with a breast cancer diagnosis in a sister was 1.40-fold (95% CI, 1.31-fold to 1.48-fold) using the static method, 1.66-fold (95% CI, 1.57-fold to 1.76-fold) using the accumulative method, and 2.28-fold (95% CI, 2.07-fold to 2.51-fold) using the dynamic method.Conclusions: The results of the current study demonstrated that assessing family history as static, accumulative, or dynamic results in different familial risk estimates. The answer as to which method to use for family history assessment depends on the implications of the study, with the dynamic method appearing to be better suited for risk stratification studies, the accumulative method being the most convenient in practice and the least favored for risk prediction, and the static method being suitable for etiological impact and risk attribution studies. [ABSTRACT FROM AUTHOR]

Background: Faecal immunochemical tests (FITs) have replaced guaiac-based faecal occult blood test (gFOBTs) in several colorectal cancer (CRC) screening programmes. We aimed to evaluate the benefits of this transition based on the Wallonia-Brussels-organised CRC screening programme.Methods: A total of 1,569,868 individuals aged 50-74 years, who were invited to screening during 2009-2017, were studied by linking their screening records with insurance, pathology and cancer data in the Belgian Cancer Registry. We compared neoplasm detection rates and positive predictive values (PPVs) of gFOBT and FIT at 15 µg haemoglobin per gram cut-off in screen-naive individuals. We furthermore examined the incidence rates of interval cancer in gFOBT- and FIT-based screening programme.Results: Advanced neoplasms were detected less frequently by gFOBT (0.8%) than by FIT (1.3%), with a difference of 0.5% (P < 0.01). PPVs were lower for gFOBT (15.1%) than for FIT (21.7%) for advanced neoplasms (difference 6.6%, P < 0.01). Compared to participants with negative gFOBT, those with negative FIT were 77% less likely to develop interval cancer (incidence rate ratio 0.23, 95% confidence interval 0.16-0.33).Conclusion: Our study demonstrated that in an organised CRC screening programme, replacing gFOBT with FIT improved neoplasm detection rate and substantially reduced interval cancer incidence. [ABSTRACT FROM AUTHOR]

Background: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk.Methods: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided.Results: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes.Conclusion: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach.Methods: Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk.Results: Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors.Conclusions: In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development. [ABSTRACT FROM AUTHOR]

Background: Previous research suggests an age differential in health-related quality of life (HRQOL) among long-term (5–10 years post-diagnosis, LTS) colorectal cancer (CRC) survivors. Few studies have specifically addressed the association of age differentials with HRQOL for very long-term CRC survivors (>10 years post-diagnosis, VLTS) and non-cancer population controls. We aimed to assess possible deficits in HRQOL of disease-free CRC-LTS and CRC-VLTS in comparison with non-cancer population controls, and whether the observed pattern varies by age and time since diagnosis. Methods: We used data from the CAncEr Survivorship - A multi-Regional (CAESAR+) study in collaboration with five population-based German cancer registries. HRQOL from controls was accessed from the Lebensqualität in DEeutschland (LinDE) study. All respondents completed the European Organization for Research and Treatment of Cancer Quality of Life Core-30 questionnaire. We calculated least square means of HRQOL scores. Analyses were adjusted for age, sex, and education, where appropriate. Results: The sample included 862 CRC-LTS, 400 CRC-VLTS and 1689 controls. CRC survivors reported overall good HRQOL but significantly poorer social functioning and more problems with dyspnea, constipation, diarrhea and finances than controls. When stratified by age, deficits in functioning and global health, and more problems with symptoms and finances were noted mainly among younger CRC survivors. Further stratification by time since diagnosis showed that similar deficits in HRQOL and symptoms were noted mainly among the younger CRC-LTS group when compared with controls. Generally, CRC-VLTS reported comparable HRQOL to controls. An exception was noted for diarrhea, whereby CRC survivors, regardless of age and time since diagnosis, reported significantly more problems with this symptom than controls. Conclusions: In comparison with non-cancer controls, disease-free CRC survivors reported overall good HRQOL but experience persistent specific detriments in HRQOL many years after diagnosis. In age stratified analyses, HRQOL deficits were noted mainly among younger CRC-LTS. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.Methods: We used individual-level data from six large breast cancer case-cohorts including a total of 36 210 individuals (2475 events) of European ancestry. We created a BMI genetic risk score (GRS) based on genotypes at 94 known BMI-associated genetic variants. Association between the BMI genetic score and breast cancer survival was analysed by Cox regression for each study separately. Study-specific hazard ratios were pooled using fixed-effect meta-analysis.Results: BMI genetic score was found to be associated with reduced breast cancer-specific survival for estrogen receptor (ER)-positive cases [hazard ratio (HR) = 1.11, per one-unit increment of GRS, 95% confidence interval (CI) 1.01-1.22, P = 0.03). We observed no association for ER-negative cases (HR = 1.00, per one-unit increment of GRS, 95% CI 0.89-1.13, P = 0.95).Conclusions: Our findings suggest a causal effect of increased BMI on reduced breast cancer survival for ER-positive breast cancer. There is no evidence of a causal effect of higher BMI on survival for ER-negative breast cancer cases. [ABSTRACT FROM AUTHOR]

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer.Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions.Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height >180 cm are at a 22% increased risk as compared to men with height <173 cm (OR 1.22, 95% CI 1.01-1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group.Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs.Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures. [ABSTRACT FROM AUTHOR]

Background. Rectal cancer (RC) is a common malignancy with a substantial mortality but good survival for patients with optimally treated nonmetastatic disease. Lack of insurance may compromise access to care and therefore compromise survival. Here, we examine RC survival by insurance type. Methods. Data from the Surveillance, Epidemiology, and End Results database were used to determine 1- to 3-year survival for patients with RC by insurance type (Medicaid, uninsured, other insurance). Results. Patients with Medicaid or no insurance presented at later stages and were less likely to receive definitive surgery. Overall 3-year survival was higher for patients with other insurance compared with Medicaid-insured (122.2% units) and uninsured (118.8% units) patients. Major differences in survival were still observed after adjustment for stage. When patients with stage II and III RC were considered, 3-year survival was higher for patients with other insurance versus those with Medicaid (116.2% units) and uninsured patients (112.2% units). However, when the analysis was limited to patients with stage II and III disease who received radiation therapy followed by definitive surgery, the difference decreased to 111.8% units and 17.3% units, respectively, for Medicaid and no insurance. Conclusion. For patients with stage II and III RC, much of the difference in survival between uninsured patients and those with insurance other than Medicaid can be explained by differences in treatment. Further efforts to determine the cause of residual differences as well as efforts to improve access to standard-of-care treatment for uninsured patients may improve population-level survival for RC. [ABSTRACT FROM AUTHOR]

Objectives To investigate the relationship between polypharmacy and frailty. Design Longitudinal, observational cohort study. Setting Saarland, Germany. Participants 3,058 community-dwelling adults aged between 57 and 84 years. Measurements Frailty was assessed according to the frailty phenotype, described by Fried et al. Polypharmacy and hyperpolypharmacy were defined as the concomitant use of five or more and 10 or more drugs, respectively. We assessed associations between polypharmacy and prevalent and incident frailty within 3 years of follow-up by logistic regression models controlled for multiple potential confounders including comorbidity. Additionally, cubic splines were used to assess dose-response associations. Results Polypharmacy was reported in 39.1% (n = 1,194), and hyperpolypharmacy in 8.9% (n = 273) of participants. Prevalent frailty was present in 271 (8.9%) participants; 186 (9.3%) of 1,998 non-frail participants with follow-up data became frail within 3 years. After adjustment, polypharmacy and hyperpolypharmacy were associated with prevalent frailty with adjusted odds ratios (95% confidence interval) of 2.30 (1.60-3.31) and 4.97 (2.97-8.32), respectively. Polypharmacy (odds ratio ( OR) 1.51 (1.05-2.16)) and hyperpolypharmacy ( OR 1.90 (1.10-3.28)) were also independent predictors of incident frailty. Furthermore, there was a moderate exposure-response relationship between the number of medicines and prevalent as well as incident frailty. Conclusion Our study showed that polypharmacy is associated with frailty. Further research should address the potential benefit of reducing of inappropriate polypharmacy and better pharmacotherapeutic management for preventing medication-associated frailty. [ABSTRACT FROM AUTHOR]

Physical activity (PA) and vitamin D are thought to affect colorectal cancer prognosis. The present study investigates associations between 25(OH)D3 and PA in prospectively followed colorectal cancer patients in the ColoCare study. At 6, 12, and 24 mo after surgery, patients donated a blood sample, wore an accelerometer for 10 consecutive days, and completed a PA questionnaire. Plasma 25-hydroxyvitamin D3 (25(OH)D3) levels were measured by high-performance liquid chromatography. We tested associations using partial correlations and multivariate linear regression analysis, adjusted for season, age, and body mass index. A total of 137 assessments of 25(OH)D3 levels and PA were conducted (58 at 6 mo, 51 at 12 mo, and 28 at 24 mo). More than 60% of the patients were vitamin D-deficient (25(OH)D3 ≤20 ng/ml), independent of study time point. At 6-mo follow-up, accelerometry-based vigorous and moderate-to-vigorous PAs were positively associated with 25(OH)D3 levels (P = 0.04; P = 0.006,). PA together with season was a significant predictor of elevated 25(OH)D3 levels. Our results suggest that the majority of colorectal cancer patients may suffer from vitamin D deficiency. Engaging in PA may be an effective approach to increase their 25(OH)D3 levels. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between body mass index (BMI) and colorectal cancer (CRC) prognosis after diagnosis have yielded inconsistent results. Few studies have investigated associations between prediagnostic BMI change and CRC prognosis. Objective: The associations of BMI at diagnosis and prediagnostic BMI change with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design: A total of 3130 patients diagnosed with CRC between 2003 and 2010 were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.9 y. With the use of Cox proportional hazards regression, associations between BMI at diagnosis and BMI change (difference between 1-10 y before diagnosis and at diagnosis) and overall, CRC-specific, recurrence-free, and diseasefree survival were analyzed. Results: Compared with normal weight, overweight [BMI (in kg/m²): 25 to <30] and obesity (BMI: ≥30) were associated with improved overall [adjusted HR (aHR): 0.82; 95% CI: 0.70, 0.95 and aHR: 0.80; 95% CI: 0.66, 0.98, respectively] and CRC-specific (aHR: 0.84; 95% CI: 0.71, 1.01 and aHR: 0.78; 95% CI: 0.62, 0.99, respectively) survival, with associations being even stronger when the analysis was restricted to nonmetastatic disease. Compared with stable BMI, a strong prediagnostic BMI decrease of >5 was associated with poorer prognosis for all survival outcomes (overall survival-- aHR: 1.83; 95% CI: 1.43, 2.34; CRC-specific survival--aHR: 1.78; 95% CI: 1.33, 2.39), and associations were particularly pronounced in men (overall survival--aHR: 2.31; 95% CI: 1.65, 3.22; CRC-specific survival--aHR: 2.56; 95% CI: 1.72, 3.81; P-interaction = 0.08). Conclusions: Overweight and obesity are associated with enhanced survival after a CRC diagnosis. A major decrease in BMI in the years before diagnosis is a strong independent predictor of decreased survival. [ABSTRACT FROM AUTHOR]

Background: Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. Objective: The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design: In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. Results: In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: >0-12 g/d; men: >0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. Conclusions: Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Menopausal hormone therapy (MHT) use has been consistently associated with a decreased risk of colorectal cancer (CRC) in women. Our aim was to use a genome-wide gene-environment interaction analysis to identify genetic modifiers of CRC risk associated with use of MHT.Methods: We included 10 835 postmenopausal women (5419 cases and 5416 controls) from 10 studies. We evaluated use of any MHT, oestrogen-only (E-only) and combined oestrogen-progestogen (E+P) hormone preparations. To test for multiplicative interactions, we applied the empirical Bayes (EB) test as well as the Wald test in conventional case-control logistic regression as primary tests. The Cocktail test was used as secondary test.Results: The EB test identified a significant interaction between rs964293 at 20q13.2/CYP24A1 and E+P (interaction OR (95% CIs)=0.61 (0.52-0.72), P=4.8 × 10(-9)). The secondary analysis also identified this interaction (Cocktail test OR=0.64 (0.52-0.78), P=1.2 × 10(-5) (alpha threshold=3.1 × 10(-4)). The ORs for association between E+P and CRC risk by rs964293 genotype were as follows: C/C, 0.96 (0.61-1.50); A/C, 0.61 (0.39-0.95) and A/A, 0.40 (0.22-0.73), respectively.Conclusions: Our results indicate that rs964293 modifies the association between E+P and CRC risk. The variant is located near CYP24A1, which encodes an enzyme involved in vitamin D metabolism. This novel finding offers additional insight into downstream pathways of CRC etiopathogenesis. [ABSTRACT FROM AUTHOR]

BACKGROUND: With epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified. OBJECTIVES: We aimed to assess dose--response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality. METHODS: In a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Illumina 450K assay. Deaths were recorded during a median follow-up of 10.3 years. Dose--response relationships of smoking exposure with methylation at nine CpGs were modeled by restricted cubic spline regression. Associations of individual and aggregate methylation patterns with all-cause, cardiovascular, and cancer mortality were assessed by multiple Cox regression. RESULTS: Clear dose--response relationships with respect to current and lifetime smoking intensity were consistently observed for methylation at six of the nine CpGs. Seven of the nine CpGs were also associated with mortality outcomes to various extents. A methylation score based on the top two CpGs (cg05575921 and cg06126421) showed the strongest associations with all-cause, cardiovascular, and cancer mortality, with adjusted hazard ratios (95% CI) of 3.59 (2.10, 6.16), 7.41 (2.81, 19.54), and 2.48 (1.01, 6.08), respectively, for participants with methylation levels in the lowest quartile at both CpGs. Adding methylation at those two CpGs into a model that included the variables of the Systematic Coronary Risk Evaluation chart for fatal cardiovascular risk prediction improved the predictive discrimination. CONCLUSION: The novel methylation biomarkers are highly informative for both smoking exposure and smoking-related mortality outcomes. In particular, these biomarkers may substantially improve cardiovascular risk prediction. Nevertheless, the findings of the present study need to be further validated in additional large longitudinal studies. [ABSTRACT FROM AUTHOR]

Background: Little is known about the prognostic impact of red and processed meat intake or about changes in consumption after a diagnosis of colorectal cancer (CRC). Objectives: We investigated associations of baseline red and processed meat with survival outcomes and explored changes in intake among CRC survivors 5 y after diagnosis. Design: A total of 3122 patients diagnosed with CRC between 2003 and 2010 were followed for a median of 4.8 y [DACHS (Darmkrebs: Chancen der Verhütung durch Screening) study]. Patients provided information on diet and other factors in standardized questionnaires at baseline and at the 5-y follow-up. Cox proportional hazards regression models were used to estimate HRs and 95% CIs. Results: Among patients with stage I-III CRC, baseline red and processed meat intake was not associated with overall (>1 time/d compared with <1 time/d; HR: 0.85; 95% CI: 0.67, 1.09), CRC-specific (HR: 0.83; 95% CI: 0.61, 1.14), cardiovascular disease-specific (HR: 0.92; 95% CI: 0.51, 1.68), non-CRC-specific (HR: 0.88; 95% CI: 0.59, 1.30), and recurrence-free (HR: 1.03; 95% CI: 0.80, 1.33) survival; results among stage IV patients were comparable. An association with worse overall survival was found among patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated CRC (HR: 1.99; 95% CI: 1.10, 3.56) but not with microsatellite instability or CpG island methylator phenotype (CIMP) positivity. A much lower proportion of survivors reported daily consumption of red and processed meat at the 5-y follow-up than at baseline (concordance rate: 39%; κ-value: 0.10; 95% CI: 0.07, 0.13). Conclusions: Our findings suggest that baseline red and processed meat intake is not associated with poorer survival among patients with CRC. The potential interaction with KRAS mutation status warrants further evaluation. Major changes in consumption measured at the 5-y follow-up may have had an impact on our survival estimates. [ABSTRACT FROM AUTHOR]

Background: imbalances in metabolic, inflammatory and redox homeostasis play an important role in the leading theories of age-related morbidity, but no large-scale epidemiological study has been conducted so far assessing their associations with total morbidity and multi-morbidity in the same model. Methods: analyses were conducted in 2,547 participants of an established population-based cohort study from Germany. The participants' median age was 70 years (range: 57-84) and 51.9% were women. End points were total somatic morbidity and multi-morbidity, assessed by the Cumulative Illness Rating Scale-Geriatric version. Results: overall, 251 study participants had multi-morbidity (9.9%). Except for the redox marker 'total thiol levels of proteins', all other assessed metabolic (obesity, diabetes, dyslipidaemia and hypertension), inflammatory (C-reactive protein) and oxidative stress markers (derivatives of reactive oxygen metabolites) were significantly associated with total somatic morbidity and multi-morbidity if assessed individually. If modelled jointly, effect estimates were attenuated but remained statistically significant for the outcome 'total morbidity' and for low weight, obesity, insufficiently controlled diabetes and derivatives of reactive oxygen metabolites with respect to the outcome 'multi-morbidity'. Conclusions: results from this large sample of older adults support hypotheses that relate imbalances in metabolic, inflammatory and redox homeostasis to age-related morbidity. Despite over adjustment for closely related metabolic, inflammatory and oxidative stress conditions in the full model, independent associations of the markers with total morbidity and/or multi-morbidity were observed. Therefore, adverse metabolic, inflammatory and oxidative stress conditions may all play important roles in the pathogenesis of age-related morbidity, which should be investigated further in future longitudinal studies. [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]

Purpose: We investigated the prevalence and quality of medication schedules of elderly ambulatory patients and assessed factors associated with the availability of a medication schedule. In particular, we evaluated whether sending out a blank medication schedule template would increase the chances to use such a document. Methods: Data originate from the ESTHER study, a cohort study conducted in Saarland, Germany, in which trained study physicians performed home visits. They scanned all medication schedules, recorded the participants' medication, and performed thorough geriatric assessments. As part of the intervention, a blank medication schedule template along with a brochure was mailed to half of the participants (intervention group) 4 weeks prior to the home visits. Results: In total, 553 of 2470 participants (22.4 %) had a medication schedule. Almost two thirds of the schedules were issued by health care professionals ( n = 353, 63.8 %). These schedules offered a higher quality, although important information such as over-the-counter (OTC) medication was regularly missing. Self-reported adherence was higher in participants who used self-issued medication schedules; however, self-reported medication adherence in patients with any medication schedule was poorer compared to those patients not using a schedule. Factors associated with the availability of a medication schedule were male sex, a higher number of medicines to take, and a more complex drug regimen. The intervention did not increase the number of patients having a medication schedule. Conclusion: Only a minority of elderly ambulatory patients had a medication schedule at home. Sending out a brochure along with a blank medication schedule template did not increase the prevalence of medication schedules. [ABSTRACT FROM AUTHOR]

Background: excess weight is a risk factor for numerous co-morbidities that predominantly occur in later life. This study's purpose was to analyse the association between excess weight and health service use/costs in the older population in Germany. Methods: this cross-sectional analysis used data of n = 3,108 individuals aged 58--82 from a population-based prospective cohort study. Body mass index (BMI) and waist-to-height ratio (WHtR) were calculated based on clinical examinations. Health service use was measured by a questionnaire for a 3-month period. Corresponding costs were calculated applying a societal perspective. Results: 21.8% of the sample were normal weight, 43.0% overweight, 25.5% obese class 1 and 9.6% obese class ≥2 according to BMI. In 42.6%, WHtR was ≥0.6. For normal weight, overweight, obese class 1 and obese class ≥2 individuals, mean costs (3-month period) of outpatient care were 384€, 435€, 475€ and 525€ (P < 0.001), mean costs of inpatient care were 284€, 408€, 333 € and 652€ (P= 0.070) and mean total costs 716€, 891€, 852€ and 1,244€ (P= 0.013). For individuals with WHtR <0.6 versus ≥0.6, outpatient costs were 401€ versus 499€ (P< 0.001), inpatient costs 315€ versus 480€ (P= 0.016) and total costs 755€ versus 1,041€ (P< 0.001). Multiple regression analyses controlling for sociodemographic variables showed a significant effect of obesity on costs of outpatient care (class 1: +72€; class ≥2: +153€) and total costs (class ≥2: +361€) while the effect of overweight was not significant. WHtR ≥0.6 significantly increased outpatient costs by +79€ and total costs by +189€. Conclusions: excess weight is associated with increased service use and cost in elderly individuals, in particular in obese class ≥2 individuals. [ABSTRACT FROM AUTHOR]

Background: cognitive impairment is widespread among older adults even in the absence of dementia, but very little is known about the association between cognitive impairment not due or not yet converted to dementia and mortality. The association between cognitive impairment and mortality contributes to assessing cognitive impairment-related risk constellation in old age in the absence of manifest dementia. Objective: to assess the impact of cognitive impairment on all-cause and cause-specific mortality among non-demented older adults and to explore the nature of the association between cognitive impairment and mortality. Design: an observational cohort study (ESTHER study; 2000--present). Setting: German state of Saarland. Subjects: a subsample of 1,622 participants aged ≥70 with measurement of cognitive function through the Cognitive Telephone Screening Instrument (COGTEL) and exclusion of a possible dementia diagnosis at both COGTEL baseline (2005-08) and over the mortality follow-up (2005-13). Results: during an average follow-up of 6.1 years, 231 participants (14.2%) died. Participants with low COGTEL total scores had ~60% increased mortality compared with participants with higher COGTEL total scores in Cox regression models adjusting for a wide range of possible confounders (hazard ratio = 1.62; confidence interval 1.13-2.33). Dose--response analyses with restricted cubic splines indicate a monotonic inverse relationship between cognitive function and mortality. Conclusion: cognitive impairment in the absence of manifest dementia is an important independent predictor of mortality, especially among men. The administration of cognitive tests among older adults may provide relevant information for patient care and treatment decisions. Sources of funding: financial sponsors played no role in the design, execution, analysis and interpretation of data. [ABSTRACT FROM AUTHOR]

Background/Aims: Very few studies have investigated the longitudinal association between serum levels of 25-hydroxyvitamin D [25(OH)D] and cognitive impairment not due to dementia. This longitudinal study analysed 25(OH)D and the risk of cognitive decline among non-demented older adults. Methods: A subsample of the ESTHER cohort study, aged ≥70 years, was assessed with the Cognitive Telephone Screening Instrument (COGTEL) and underwent 25(OH)D measurements standardized with a reference method (n = 1,302). After an average follow-up of 4.6 years, 527 participants had repeated COGTEL testing and were eligible for analysis. Linear regression models were used to assess longitudinal associations between 25(OH)D levels and cognitive function. Possible practice effects of repeated cognitive testing were addressed with the reliable change index. Results: A trend of a more pronounced cognitive decline with lower vitamin D levels was observed among both women and men, with a statistically significant difference in COGTEL scores in the lowest vitamin D quintile of the total sample. Conclusions: This study indicates that low levels of vitamin D might be associated with cognitive decline among non-demented elderly individuals and highlights the need for further large-scale prospective studies to clarify the potential role of vitamin D in cognitive function at an old age. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Recent genome-wide DNA methylation studies have found a pronounced difference in methylation of the F2RL3 gene (also known as PAR-4) in blood DNA according to smoking exposure. Knowledge on the variation of F2RL3 methylation by various degrees of smoking exposure is still very sparse. Objectives: We aimed to assess dose-response relationships of current and lifetime active smoking exposure with F2RL3 methylation. Methods: In a large population-based study, we quantified blood DNA methylation at F2RL3 for 3,588 participants using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Associations of smoking exposure with methylation intensity were examined by multiple linear regression, controlling for potential confounding factors and paying particular attention to dose-response patterns with respect to current and lifetime smoking exposure as well as time since cessation of smoking. Results: F2RL3 methylation intensity showed a strong association with smoking status (p < 0.0001), which persisted after controlling for potential confounding factors. Clear inverse dose-response relationships with F2RL3 methylation intensity were seen for both current intensity and lifetime pack-years of smoking. Among former smokers, F2RL3 methylation intensity increased gradually from levels close to those of current smokers for recent quitters to levels close to never smokers for long-term (> 20 years) quitters. Conclusions: F2RL3 methylation is a promising biomarker for both current and long-term past tobacco exposure, and its predictive value for smoking-related diseases warrants further exploration. [ABSTRACT FROM AUTHOR]

Introduction In order to limit rising publicly-financed health expenditure, out-of-pocket payments for health care services (OOPP) have been raised in many industrialized countries. However, higher health-related OOPP may burden social subgroups unequally. In Germany, inequalities in OOPP have rarely been analyzed. The aim of this study was to examine OOPP of the German elderly population in the different sectors of the health care system. Socio- economic and morbidity-related determinants of inequalities in OOPP were analyzed. Methods This cross-sectional analysis used data of N = 3,124 subjects aged 57 to 84 years from a population-based prospective cohort study (ESTHER study) collected in the Saarland, Germany, from 2008 to 2010. Subjects passed a geriatric assessment, including a questionnaire for health care utilization and OOPP covering a period of three months in the following sectors: inpatient care, outpatient physician and non-physician services, medical supplies, pharmaceuticals, dental prostheses and nursing care. Determinants of OOPP were analyzed by a two-part model. The financial burden of OOPP for certain social subgroups (measured by the OOPP-income-ratio) was investigated by a generalized linear model for the binomial family. Results Mean OOPP during three months amounted to €119, with 34% for medical supplies, 22% for dental prostheses, 21% for pharmaceuticals, 17% for outpatient physician and non-physician services, 5% for inpatient care and 1% for nursing care. The two-part model showed a significant positive association between income (square root equivalence scale) and total OOPP. Increasing morbidity was associated with significantly higher total OOPP, and in particular with higher OOPP for pharmaceuticals. Total OOPP amounted to about 3% of disposable income. The generalized linear model for the binomial family showed a significantly lower financial burden for the wealthiest quintile as compared to the poorest one. Conclusions This is the first study providing evidence of inequalities in OOPP in the German elderly population. Socio-economic and morbidity-related inequalities in OOPP and the resulting financial burden could be identified. The results of this study may contribute to the discussion about the mechanisms causing the observed inequalities and can thus help decision makers to consider them when adapting future regulations on OOPP. [ABSTRACT FROM AUTHOR]

Background. Faecal immunochemical tests (FITs) for haemoglobin are increasingly used for non-invasive screening for colorectal cancer (CRC) but large scale comparative studies of different FITs for detection of CRC, overall and by stage, are sparse. We aimed to determine and compare performance of different FITs for the detection of CRC, and to assess their stage-specific sensitivities. Material and methods. We assessed sensitivity, specificity and their corresponding 95% confidence intervals for six qualitative FITs among 74 CRC cases (59% stage I or II cancers) and 1480 controls free of colorectal neoplasm. Overall and stage-specific receiver operating characteristic curves were derived for three quantitative FITs. The areas under the curves (AUCs) were calculated and compared. Results. Pairs of overall sensitivity and specificity of the qualitative FITs ranged from 66% and 96% to 92% and 62%, respectively. For the three quantitative tests, AUCs ranged from 0.90 to 0.92, with sensitivities ranging from 80% to 87% at cut-offs yielding 90% specificity. AUCs ranged from 0.85 to 0.92, 0.94 to 0.96, and 0.86 to 0.93 for stage I, stage II and advanced stages (stage III and IV) cancers, respectively. At a specificity of 90%, the tests detected 65%-85% of stage I cancers. Conclusion. The diagnostic performance of FITs regarding detection of CRC is promising, even though the pre-defined cut-offs of some of the qualitative FITs need to be adjusted to limit false-positive rates in screening setting. At cut-off levels yielding 90% specificity, the quantitative tests detected the vast majority of CRCs, even at early stages. [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]

Background: Serum 25-hydroxyvitamin D [25(OH)D] concentration has been linked to mortality in several studies, but appropriate cutoffs to define risk categories are under debate. Objective: We aimed to conduct a repeated-measurements analysis on the association of serum 25(OH)D concentrations with all-cause and cause-specific mortality, with particular attention given to the shape of dose-response relations. Design: Concentrations of 25(OH)D were measured in n = 9578 baseline and n = 5469 5-y follow-up participants of the ESTHER study, which is a German population-based cohort aged 50-74 y at baseline. Deaths were recorded during 9.5 y of follow-up (median). Restricted cubic splines were used to assess dose-response relations, and Cox regression with time-dependent variables was used to estimate hazard ratios. Results: During follow-up, 1083 study participants died; of those, 350 individuals died of cardiovascular diseases, 433 individuals died of cancer, and 55 individuals died of respiratory diseases. The overall mortality [HR (95% CI)] of subjects with vitamin D deficiency [25(OH)D concentrations <30 nmol/L] or vitamin D insufficiency [25(OH)D concentrations from 30 to 50 nmol/L) was significantly increased [1.71 (1.43, 2.03) and 1.17 (1.02, 1.35), respectively] compared with that of subjects with sufficient 25(OH)D concentrations (>50 nmol/L)]. Vitamin D deficiency was also associated with increased cardiovascular mortality [1.39 (95% CI: 1.02, 1.89)], cancer mortality [1.42 (95% CI: 1.08, 1.88)] and respiratory disease mortality [2.50 (95% CI: 1.12, 5.56)]. The association of 25(OH)D concentrations with all-cause mortality proved to be a nonlinear inverse association with risk that started to increase at 25(OH)D concentrations <75 nmol/L. Conclusions: In this large cohort study, serum 25(OH)D concentrations were inversely associated with all-cause and cause-specific mortality. In particular, vitamin D deficiency [25(OH)D concentration <30 nmol/L] was strongly associated with mortality from all causes, cardiovascular diseases, cancer, and respiratory diseases. [ABSTRACT FROM AUTHOR]

Objectives To develop and evaluate a modification of the Fried frailty assessment using population-independent cutpoints and to determine frailty prevalence of community-dwelling elderly people in a German population. Design Cross-sectional analysis of 8-year follow-up data of a large German cohort study. Setting Saarland, Germany. Participants Three thousand one hundred twelve community-dwelling adults aged 59 and older. Measurements Frailty was operationalized using modified Fried frailty criteria. Criteria were categorized according to quintiles (lowest-quintile approach) or using population-independent cutpoints derived from the literature (population-independent approach). Agreement and construct validity of frailty classification according to both approaches were evaluated according to weighted kappa (κ) and Spearman rank correlation (rSp). Associations between frailty and covariates were assessed using multiple logistic regression models. Results Although more participants were identified as frail according to the population-independent index (8.9%) than the lowest-quintile index (6.5%), agreement and correlation of frailty classification using both approaches was high (κ = 0.75 and rSp = 0.84). Sex differences in frailty prevalence were more pronounced when the population-independent approach was used (women 11.4%; men 6.1%). Similarly strong significant associations with sociodemographic, lifestyle, and medical factors such as older age, female sex, smoking, and obesity were seen for both approaches. Conclusion The modified Fried index using literature-derived cutpoints independent from the frailty criteria distributions in the underlying study population showed good correlation with the lowest-quintile approach and enables prevalence estimates that are directly comparable between different populations. [ABSTRACT FROM AUTHOR]

Purpose. Population-based studies on cervical cancer providing survival estimates by age, histology, and stage have been sparse. We aimed to derive most up-to-date and detailed survival estimates for cervical cancer patients in Germany. Methods. We used a pooled German national dataset including data from 11 cancer registries covering a population of 33 million people. Included were 15 685 patients diagnosed with cervical cancer from 1997 to 2006. Period analysis was performed to calculate the five-year relative survival (RS) 2002-2006. Trends in survival between 2002 and 2006 were examined using model-based period analysis. Age-adjustment was done using five age groups (15-44, 45-54, 55-64, 65-74, and 75 + years). Results. Overall, age-adjusted five-year relative survival in 2002-2006 was 64.7%. A strong age gradient was observed, with five-year RS decreasing from 81.7% in age group 15-49 years to 46.3% in age group 70 + years. Prognosis furthermore strongly varied by stage, with age-adjusted five-year RS reaching 84.6% for localized, 48.2% for regional, and 17.9% for distant stage. From 2002 to 2006, a significant improvement (4.7 percent units) in overall age-adjusted five-year RS was seen. The improvement was most pronounced for age groups 55-64 years (from 54.2 to 65.6%) and 65-74 years (from 50.0 to 58.1%). Conclusion. In this first comprehensive population-based study from Germany, prognosis of cervical cancer strongly varied by age and stage. Prognosis continued to improve, in particular in age range 55-74 years, in the five-year period assessed. [ABSTRACT FROM AUTHOR]

Background. Esophagus and stomach cancers are associated with poor prognosis. But most published population-based cancer survival estimates for stomach and esophagus cancer refer to survival experience of patients diagnosed in the 1990s or earlier years. The aim of this study was to provide up-to-date survival estimates and trends for patients with stomach and esophagus cancer in Germany. Material and methods. Our analysis is based on data from 11 population-based cancer registries, covering 33 million inhabitants. Patients diagnosed with stomach and esophagus cancer in 1997-2006 were included. Period analysis was used to derive five-year relative survival estimates and trends by age, sex, cancer subsite, and stage for the time period of 2002-2006. German and US survival estimates were compared utilizing the SEER 13 database. Results. Overall age-standardized five-year relative survival was 31.8% and 18.3% for stomach and esophagus cancer, respectively, compared to 27.2% and 17.4% in the US. Survival was somewhat higher among female than among male patients for both cancer sites (33.6% vs. 30.6% and 21.5% vs. 17.5%, respectively) and much higher for non-cardia stomach cancer (40.4%) than for cardia cancer (23.4%). From 2002 to 2006, a moderate increase in five-year relative survival by 2.7 percent units was observed for non-cardia stomach cancer patients in Germany (p < 0.001). Conclusion. Five-year relative cancer survival has reached levels around 40% for patients with non-cardia stomach cancer in Germany in the early 21st century, whereas it remained at lower levels around 20% for patients with esophagus and cardia cancer. [ABSTRACT FROM AUTHOR]

Evidence concerning the role of Helicobacter pylori infection in the development of colorectal cancer remains controversial. The authors assessed the association of H. pylori seroprevalence with risk of colorectal cancer in a large population-based case-control study from Germany in 2003–2007. Serum antibodies to H. pylori in general and the cytotoxin-associated gene A protein (CagA) were measured in 1,712 incident colorectal cancer cases and 1,669 controls. The association between H. pylori seroprevalence and colorectal cancer risk was estimated by logistic regression, with adjustment for potential confounders and stratification by age group, sex, anatomic subsites, and cancer stage. Overall, H. pylori seroprevalence was higher in cases (46.1%) than in controls (40.1%), resulting in an age- and sex-adjusted odds ratio of 1.30 (95% confidence interval (CI): 1.14, 1.50). Adjustment for established colorectal cancer risk factors decreased the odds ratio to 1.26 (95% CI: 1.09, 1.47), with a further reduction to 1.18 (95% CI: 1.01, 1.38) after additional adjustment for previous colorectal endoscopy. Stratified analyses showed risk elevation to be essentially confined to left-sided colorectal cancer, with an odds ratio of 1.22 (95% CI: 1.02, 1.45), suggesting that H. pylori infection may be associated with a small yet relevant risk increase in the left colorectum. [ABSTRACT FROM AUTHOR]

Background: Support for smoke-free policies increases over time and particularly after implementation of the policy. In this study we examined whether the comprehensiveness of such policies moderates the effect on support among smokers. Methods: We analysed two waves (pre- and post-smoke-free legislation) of the International Tobacco Control (ITC) surveys in France, Germany, and the Netherlands, and two pre-legislation waves of the ITC surveys in UK as control. Of 6,903 baseline smokers, 4,945 (71.6%) could be followed up and were included in the analyses. Generalised Estimating Equations (GEE) were used to compare changes in support from pre- to post-legislation to the secular trend in the control country. Multiple logistic regression models were employed to identify predictors of individual change in support. Findings: In France, the comprehensive smoking ban was associated with sharp increases in support for a total smoking ban in drinking establishments and restaurants that were above secular trends. In Germany and the Netherlands, where smoke-free policies and compliance are especially deficient in drinking establishments, only support for a total smoking ban in restaurants increased above the secular trend. Notable prospective predictors of becoming supportive of smoking bans in these countries were higher awareness of cigarette smoke being dangerous to others and weekly visiting of restaurants. Conclusions: Our findings suggest that smoke-free policies have the potential to improve support once the policy is in place. This effect seems to be most pronounced with comprehensive smoking bans, which thus might be the most valid option for policy-makers despite their potential for creating controversy and resistance in the beginning. [ABSTRACT FROM AUTHOR]

Purpose. To investigate the age-specific pattern of administration of chemotherapy and its association with long-term survival and quality of life (QoL) in stage II and III colorectal cancer patients. Methods. Chemotherapy allocation according to disease and patient characteristics was investigated in a population-based cohort of 562 stage II and III colorectal cancer patients. Five years after diagnosis, survival was determined and QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and a tumor specific module. The association among chemotherapy, survival, and QoL was examined while controlling for potential confounders. Results. Chemotherapy was administered in 71% of patients aged <60 years and in only 20% of patients aged ≥80 years. A significant association between chemotherapy and longer survival time was found for stage III cancer only. Chemotherapy was associated with higher symptom levels for trouble with taste, anxiety, and hair loss. In age-specific analyses, younger survivors (<70 years at time of follow-up) with a history of chemotherapy reported significantly lower physical, role, and cognitive functioning and higher pain, appetite loss, hair loss, and trouble with taste symptom levels. In contrast, for older survivors (≥70 years), only two (hair loss and dry mouth) out of 38 QoL scores were significantly associated with chemotherapy. Discussion. Chemotherapy is associated with lower long-term QoL, especially in younger survivors. In cases of uncertain survival benefits of chemotherapy, consideration of its long-term effects on QoL should be incorporated into final decisions on treatment. [ABSTRACT FROM AUTHOR]

The sojourn time of preclinical colorectal cancer is a critical parameter in modeling effectiveness and cost-effectiveness of colorectal cancer screening. For ethical reasons, it cannot be observed directly, and available estimates are based mostly on relatively small historic data sets that do not include differentiation by age and sex. The authors derived sex- and age-specific estimates (age groups: 55–59, 60–64, 65–69, 70–74, 75–79, and ≥80 years) of mean sojourn time, combining data from the German national screening colonoscopy registry (based on 1.88 million records) and data from population-based cancer registries (population base: 37.9 million people) for the years 2003–2006. Estimates of mean sojourn time were similar for both sexes and all age groups and ranged from 4.5 years (95% confidence interval: 4.1, 4.8) to 5.8 years (95% confidence interval: 5.3, 6.3) for the subgroups assessed. Sensitivity analyses indicated that mean sojourn time might be approximately 1.5 years longer if colorectal cancer prevalence in nonparticipants of screening colonoscopy is 20% lower than prevalence in participants or 1 year shorter if it exceeds the prevalence in participants by 20%. This study provides, for the first time, precise estimates of sojourn time by age and sex, and it suggests that sojourn times are remarkably consistent across age groups and in both sexes. [ABSTRACT FROM PUBLISHER]

Background: The EUROCARE study has disclosed large variations of survival across Europe, with the magnitude varying, depending on cancer site. Comparisons of these rates with those from the developing countries are rare, but important in evaluating international cancer care discrepancies. This study aimed to provide up-to-date estimates of cancer survival in a Philippine urban population, and to compare these with those observed in the European countries. Methods: Using the results from the EUROCARE-4 study, the survival estimates of the European patients who were diagnosed in 1995–99 and followed till December 2003 were abstracted. From randomly selected samples drawn from the Manila and Rizal Cancer Registries, 5-year survival was estimated for nine common cancers. Age-adjusted survival estimates were then compared between the Philippine population and Europeans. Results: In comparison to the European mean, survival estimates for the Philippine residents were lower for most cancers, with differences ranging from 2 to 40% units. Differences with European country-specific estimates were large for cancers of the breast and cervix, where early detection is possible, and for leukaemia, where treatment regimens are costly, highlighting the importance of health care. Smaller discrepancies were observed for stomach, liver and lung cancers, with the 5-year relative survival being similar to the Philippines and to many European countries. A survival advantage was seen though for the Philippine residents for ovarian cancer. Conclusion: Apart from efforts to prevent cancers, improvements in cancer control and making early diagnosis and treatment more accessible remain major challenges, both in the Philippines and in the European nations. [ABSTRACT FROM AUTHOR]

Background. International comparisons have pointed to very low survival of patients diagnosed with testicular cancer (TC) in Estonia. Methods. Using population based data from the Estonian Cancer Registry and period analysis, we examined trends in TC survival between 1985 and 2004. Additional results from a review of clinical records to ascertain patterns of disease management (1990-2003) were used to explain the changes and identify the areas for potential improvement. Results. Age-adjusted 5-year period relative survival increased from 47.9% in 1985-1989 to 74.5% in 2000-2004 (p for trend <0.01). A marked improvement was seen for the patients younger than 30, with the 5-year survival reaching 93.3%, while the improvement remained modest among patients aged 30 and above. Although substantial advances occurred in staging and treatment techniques since 1990, deficiencies remained evident in disease management, including not referring patients to an oncologist after their orchiectomy and less careful diagnostic workup for patients above 30 years of age. Low use of radiotherapy suggests poor access to contemporary equipment. Delays in seeking medical consultation, but also in starting adjuvant therapy, could have contributed to poorer outcomes. Conclusions. Survival in TC increased markedly in Estonia by the 21st century, but is still notably lower than in the more developed countries. Multidisciplinary efforts may help to achieve further improvement. The provision of TC care should be coordinated by specialised cancer centres. [ABSTRACT FROM AUTHOR]

Aims: The study of cognitive functioning in large epidemiological settings is hampered by a lack of instruments for the remote assessment of cognitive performance, especially when targeting variability across the full range of adult functioning. The present study examined the practicability of such investigations using a recently developed telephone interview (Cognitive Telephone Screening Instrument, COGTEL). Methods: A subcohort of an ongoing epidemiological study in the elderly German population (ESTHER) was interviewed via telephone by trained personnel. These data were combined with sociodemographic information obtained by standardized self-administered questionnaires, and analysed by tabulation, histograms and regression models. Results: A total of 1,697 interviews could be analysed. The eligible participants had a mean age ± standard deviation of 74.0 ± 2.8 years. The COGTEL total scores closely followed a normal distribution with no evidence of a ceiling effect. In adjusted regression models, COGTEL total and subcomponent scores were negatively associated with age and strongly positively with higher education, whereas the association with sex was less consistent. Conclusions: The results suggest that the COGTEL can readily be administered to large study populations and produces plausible and informative results. Education should be considered in all investigations using this instrument and requires further in-depth analyses. Future studies will need to elucidate its associations with risk factors and its prognostic potential for cognitive decline and dementia. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Several therapies for localised prostate cancer (PC) are available; all yield similar survival rates. However, each therapy has significant side effects that can influence patients' health‐related quality of life (HRQoL) in the long run. Methods: The study sample included 911 survivors with localised PC, 5–15 years post‐diagnosis who were identified from the population‐based CAESAR + study in Germany. HRQoL was assessed using the EORTC QLQ‐C30 and EORTC QLQ‐PR25 questionnaires. The association between type of therapy and HRQoL was assessed with multivariable linear regression and global F‐test adjusting for age, time since diagnosis and comorbidities. Results: Overall, survivors treated with radical prostatectomy (RP) or radiotherapy (RT) alone reported the best HRQoL and the lowest symptom burden. Conversely, survivors treated with androgen deprivation therapy (ADT) (& RP/RT) or RP & RT (in combination) reported the worst HRQoL and the highest symptom burden. Significant differences among treatment groups in HRQoL were found for global health status (p = 0.041), social functioning (p = 0.007), urinary symptoms (p = 0.035), bowel symptoms (p = 0.017) and hormonal treatment‐related symptoms (p < 0.001) among other symptoms. Conclusions: Long‐term localised PC survivors formerly treated with a combination of RP and RT or with ADT report poorer HRQoL and more symptoms than patients treated with either RP or RT alone. [ABSTRACT FROM AUTHOR]

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: Breastfeeding is an important determinant of early infant immune function and potentially future health. Although numerous studies have reported rising breastfeeding initiation rates and duration, few longitudinally investigated the impact of shifting societal and lifestyle factors on breastfeeding patterns in developed nations. METHODS: The Ulm Birth Cohort Study (UBCS) and Ulm SPATZ Health Study (SPATZ) cohorts consist of newborns and their mothers recruited, respectively, from 2000 to 2001 and 2012 to 2013 at the University Medical Center Ulm, Germany. Cox proportional hazards models were used to estimate crude and mutually adjusted hazard ratios for study effect (time trend) and individual risk factors on noninitiation and duration of predominant and total breastfeeding. RESULTS: Compared with UBCS mothers, SPATZ mothers had lower cessation rates of both predominant breastfeeding by 4 months and total breastfeeding by 6 months: hazard ratio (95% confidence interval) 0.79 (0.67-0.93) and 0.71 (0.60-0.82), respectively. However, this crude time trend was limited to mothers with higher educational achievement. Similar time trend effects were observed among less educated mothers only after adjustment for early cessation risk factors. Mutually adjusted hazard ratios for individual risk factors were similar in both studies: low education, high BMI, smoking within 6 weeks of delivery, and cesarean delivery were associated with early breastfeeding cessation beginning at 6 weeks. In addition, actively abstaining from drinking alcohol was associated with lower rates of early cessation. CONCLUSIONS: Our results suggest widening socioeconomic disparity in breastfeeding and potentially subsequent child health, which may require new targeted interventions. [ABSTRACT FROM AUTHOR]