Germline BRCA2 K3326X and CHEK2 I157T mutations increase risk for sporadic pancreatic ductal adenocarcinoma.

Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values <0.05 considered significant. K3326X and I157T were associated with increased risk of developing sporadic PDAC (odds ratio (ORdom ) = 1.78, 95% confidence interval (CI) = 1.26-2.52, p = 1.19 × 10-3 and ORdom = 1.74, 95% CI = 1.15-2.63, p = 8.57 × 10-3 , respectively). Neither mutation was significantly associated with risk of developing early-onset PDAC. This retrospective study demonstrates novel risk estimates of K3326X and I157T in sporadic PDAC which suggest that upon validation and in combination with other established genetic and non-genetic risk factors, these mutations may be used to improve pancreatic cancer risk assessment in European populations. Identification of carriers of these risk alleles as high-risk groups may also facilitate screening or prevention strategies for such individuals, regardless of family history.

Association of generalized anxiety symptoms and panic with health care costs in older age-Results from the ESTHER cohort study.

BACKGROUND: Little is known specifically about the association between generalized anxiety symptoms or panic and health care costs in older age. The aim of this study was to examine the association between generalized anxiety symptoms, panic and health care costs in people aged 65 and over. METHODS: Cross-sectional data from the 8-year follow-up of a large, prospective cohort study, the ESTHER study, was used. Individuals aged 65 and over, who participated in the study's home assessment, were included in this analysis (n = 2348). Total and sectoral costs were analyzed as a function of either anxiety symptoms, probable panic disorder, or a panic attack, while controlling for selected covariates, using Two Part and Generalized Linear Models. Covariates were chosen based on Andersen's Behavioral Model of Health Care Use. RESULTS: There was no significant association between either of the anxiety or panic measures and total health care costs. Stratified by health care sectors, only the occurrence of a panic attack was significantly associated with incurring costs for outpatient non-physician services (OR: 1.99; 95% CI: 1.15-3.45) and inpatient services (OR: 2.14; 95% CI: 1.07-4.28). Other illness-related factors, such as comorbidities and depressive symptoms, were associated with health care costs in several models. LIMITATIONS: This was a cross-sectional study relying on self-reported data. CONCLUSION: This study points to an association between a panic attack and sector-specific health care costs in people aged 65 and over. Further research, especially using longitudinal data, is needed.

[Morbidity Differences by Health Insurance Status in Old Age]. / Unterschiede in der Morbidität nach Krankenversichertenstatus im Alter.

BACKGROUND: Morbidity differences between older members of private and statutory health insurance Germany have rarely been examined. Thus, we aimed at determining these differences in old age. METHODS: This study used data from 2 follow-up waves with a 3-year interval from a population-based prospective cohort study (ESTHER study) in Saarland, Germany. Morbidity was assessed by participants' GPs using a generic instrument (Cumulative Illness Rating Scale for Geriatrics). The between estimator was used which exclusively quantifies inter-individual variation. Adjusting for sex and age, we investigated the association between health insurance and morbidity in the main model. In additional models, we adjusted incrementally for the effect of education, family status and income. RESULTS: Regression models not adjusting for income showed that members of private health insurance had a lower morbidity score than members of statutory health insurance. This effect is considerably lower in models adjusting for income, but remained statistically significant (except for men). CONCLUSION: Observed differences in morbidity between older members of private and statutory health insurance can partly be explained by income differences. Thus, our findings highlight the role of model specification in determining the relation between morbidity and health insurance.

[Which Factors Affect Out-of-pocket Payments for Health Care Services Among Elderly Germans? Results of a Longitudinal Study]. / Welche Faktoren beeinflussen die privaten Zuzahlungen zu Gesundheitsleistungen im Alter? Ergebnisse einer Längsschnittstudie.

Background: In Germany, out-of-pocket payments (OOPP) account for a large proportion of total health expenditure. However, there are only few investigations on how morbidity-related, sociodemographic and lifestyle factors affect OOPP particularly in the older population. The aim of this study was to identify factors affecting OOPP for health care services among elderly Germans in a longitudinal setting. Methods: This longitudinal study used data from 2 follow-up waves (3-year interval) from a population-based prospective cohort study (ESTHER study) collected in Saarland, Germany. At the first follow-up wave, subjects were between 57 and 84 years old. Participants provided comprehensive data including individual OOPP for the preceding 3 months. Fixed effects (FE) regressions were used to determine factors affecting OOPP. Results: Mean individual OOPP (3-month period) rose from € 119 (first wave) to € 136 (second wave). Longitudinal regressions showed that higher morbidity did not affect OOPP. Moreover, changes in sociodemographic as well as lifestyle factors were not related to changes in OOPP. Solely, exemption of OOPP reduced the dependent variable significantly. Conclusion: In contrast to cross-sectional findings for Germany, OOPP are not related to morbidity and income in this study. This underlines the complex nature of OOPP in old age and the need for longitudinal studies to gain some insight into the underlying causal factors.

HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies.

BACKGROUND: To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. METHODS: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5% (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA1c was used as reference in Cox proportional hazards models. RESULTS: Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50% of the excess risk and attenuated hazard ratios (95 confidence interval) for increased HbA1c to 1.14 (1.03-1.27), 1.17 (1.00-1.37) and 1.19 (1.04-1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders. CONCLUSIONS: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.

[Treatment preferences of elderly patients with mental disorders]. / Behandlungswünsche von älteren Menschen mit psychischen Erkrankungen.

BACKGROUND: Successful treatment in psychosomatic medicine requires intrinsic motivation of the patient and the belief that the chosen therapeutic option can help. Depression, somatization disorder and generalized anxiety disorder (GAD) are frequent mental disorders in the elderly population. Finding a suitable and successful treatment for elderly people with mental disorders is often difficult. Undertreatment and the utilization of inappropriate healthcare services are frequent. OBJECTIVE: Treatment preferences of elderly patients with mental disorders were ascertained in order to evaluate the motivation for psychotherapy or other therapeutic measures. MATERIAL AND METHODS: The data were derived from the 8-year follow-up of the epidemiological study on chances of prevention, early recognition and optimized therapy of chronic diseases in the elderly population (ESTHER), a population-based cohort study in Saarland, Germany. A total of 3124 patients aged 55-84 years were included in this analysis. The treatment preferences were documented using a questionnaire with 12 different answer categories. The occurrence of depression, somatization disorder and GAD was collated using the patient health questionnaire (PHQ-D). RESULTS: Physiotherapy and inpatient rehabilitation were the most frequently named treatment preferences in all three subgroups of patients with mental disorders. Psychotherapy was the preferred treatment for 18.3 % of depressive patients, for 15.0 % of somatization patients and for 15.7 % of GAD patients. CONCLUSION: Mentally ill elderly patients in Germany preferred physical treatment techniques, such as physiotherapy and inpatient rehabilitation over psychotherapy. Discussion is needed over the reasons for these findings and the clinical implications.

Education, marital status, and risk of hip fractures in older men and women: the CHANCES project.

UNLABELLED: The role of socioeconomic status in hip fracture incidence is unclear. In a diverse population of elderly, higher education was found to be associated with lower, whereas living alone, compared to being married/cohabiting, with higher hip fracture risk. Educational level and marital status may contribute to hip fracture risk. INTRODUCTION: The evidence on the association between socioeconomic status and hip fracture incidence is limited and inconsistent. We investigated the potential association of education and marital status with hip fracture incidence in older individuals from Europe and USA. METHODS: A total of 155,940 participants (79 % women) aged 60 years and older from seven cohorts were followed up accumulating 6456 incident hip fractures. Information on education and marital status was harmonized across cohorts. Hip fractures were ascertained through telephone interviews/questionnaires or through record linkage with registries. Associations were assessed through Cox proportional hazard regression adjusting for several factors. Summary estimates were derived using random effects models. RESULTS: Individuals with higher education, compared to those with low education, had lower hip fracture risk [hazard ratio (HR) = 0.84, 95 % confidence interval (CI) 0.72-0.95]. Respective HRs were 0.97 (95 % CI 0.82-1.13) for men and 0.75 (95 % CI 0.65-0.85) for women. Overall, individuals living alone, especially those aged 60-69 years, compared to those being married/cohabiting, tended to have a higher hip fracture risk (HR = 1.12, 95 % CI 1.02-1.22). There was no suggestion for heterogeneity across cohorts (P heterogeneity > 0.05). CONCLUSIONS: The combined data from >150,000 individuals 60 years and older suggest that higher education may contribute to lower hip fracture risk. Furthermore, this risk may be higher among individuals living alone, especially among the age group 60-69 years, when compared to those being married/cohabiting.

Testicular cancer in Europe and the USA: survival still rising among older patients.

BACKGROUND: Despite high curability, some testicular cancer (TC) patient groups may have increased mortality. We provide a detailed age- and histology-specific comparison of population-based relative survival of TC patients in Europe and the USA. Design Using data from 12 European cancer registries and the USA Surveillance, Epidemiology and End Results 9 database, we report survival trends for patients diagnosed with testicular seminomas and nonseminomas between 1993-1997 and 2003-2007. Additionally, a model-based analysis was used to compare survival trends and relative excess risk (RER) of death between Europe and the USA adjusting for differences in age and histology. RESULTS: In 2003-2007, the 5-year relative survival of patients with testicular seminoma was at least 98% among those aged <50 years, survival of patients with nonseminoma remained 3%-6% units lower. Despite improvements in the relative survival of nonseminoma patients aged ≥ 50 years by 13%-18% units, survival remained markedly lower than the survival of seminoma patients of the same age. Model-based analyses showed increased RERs for nonseminomas, older, and European patients. CONCLUSIONS: There remains little room for survival improvement among testicular seminoma patients, especially for those aged <50 years. Older TC patients remain at increased risk of death, which seems mainly attributable to the lower survival among the nonseminoma patients.

Population-based survival of penile cancer patients in Europe and the United States of America: no improvement since 1990.

INTRODUCTION: Penile cancer is a rare neoplasm in Western countries, and detailed studies on trends in population-based survival of penile cancer have never been published before. We examined population-based trends in survival in Europe and the United States of America (USA). METHODS: Data from 3297 European and 1820 American penile cancer patients, contributed by 12 European cancer registries and the Surveillance, Epidemiology, and End Results (SEER) Program of the USA were included in this study. Period analysis techniques were used to examine relative survival trends overall, as well as for four geographic regions in Europe, and for the age groups 15-54, 55-64, 65-74 and 75+ for both populations between 1990-1995 and 2002-2007. Survival trends were assessed in a multiple regression model of relative excess risk including period of diagnosis, age and continent. RESULTS: The 5-year relative survival of penile cancer patients increased statistically non-significantly from 65% to 70% in Europe and decreased (significantly) from 72% to 63% in the USA. Trends in age-specific 5-year relative survival did not find any significant improvement in either Europe or the USA. The multiple regression analysis confirmed the lack of survival trend, and found significantly higher relative excess risk with age, and, apparently due to lower survival before 2002-2007, higher risk in Europe. CONCLUSION: Survival for penile cancer patients has not improved in either Europe or the USA since at least 1990. The reasons for the decrease of survival in the USA remain unknown and to be explored. Stronger international cooperation in clinical research may be important to facilitate clinical progress in treatment and thereby improvement of survival of this rare malignancy.