Depressive Symptomatology in Early Retirees Associated With Reason for Retirement-Results From the Population-Based LIFE-Adult-Study.

BACKGROUND: Transition from employment to retirement is regarded a crucial event. However, there is mixed evidence on associations between retirement and mental health, especially regarding early retirement. In Germany, cases of early retirement due to ill health-particularly, mental ill health-are increasing. Therefore, we investigated the association between early retirement and depressive symptoms, including information on different types of early retirement. METHODS: We analyzed data from 4,808 participants of the population-based LIFE-Adult-Study (age: 40-65 years, 654 retired, 4,154 employed), controlling for sociodemographic information, social network, pre-existing health conditions, and duration of retirement. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Regression analysis using entropy balancing was applied to achieve covariate balance between retired and employed subjects. RESULTS: We found no overall-differences in depressive symptoms between employed and retired persons (men: b = -.52; p = 0.431; women: b = .05; p = .950). When looking at different types of early retirement, ill-health retirement was linked to increased depressive symptoms in women (b = 4.68, 95% CI = 1.71; 7.65), while voluntary retirement was associated with reduced depressive symptoms in men (b= -1.83, 95% CI = -3.22; -.43) even after controlling for covariates. For women, statutory retirement was linked to lower depressive symptomatology (b = -2.00, 95% CI = -3.99; -.02). CONCLUSION: Depressive symptomatology among early retirees depends on reason for retirement: For women, ill-health retirement is linked to higher levels of depressive symptoms. Women who retire early due to ill-health constitute a risk group for depressive symptoms that needs specific attention in the health care and social security system.

Markov State Modelling of Disease Courses and Mortality Risks of Patients with Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) is one of the most frequent infectious diseases worldwide, with high lethality. Risk evaluation is well established at hospital admission, and re-evaluation is advised for patients at higher risk. However, severe disease courses may develop from all levels of severity. We propose a stochastic continuous-time Markov model describing daily development of time courses of CAP severity. Disease states were defined based on the Sequential Organ Failure Assessment (SOFA) score. Model calibration was based on longitudinal data from 2838 patients with a primary diagnosis of CAP from four clinical studies (PROGRESS, MAXSEP, SISPCT, VISEP). We categorized CAP severity into five disease states and estimated transition probabilities for CAP progression between these states and corresponding sojourn times. Good agreement between model predictions and clinical data was observed. Time courses of mortality were correctly predicted for up to 28 days, including validation with patient data not used for model calibration. We conclude that CAP disease course follows a Markov process, suggesting the necessity of daily monitoring and re-evaluation of patient's risk. Our model can be used for regular updates of risk assessments of patients and could improve the design of clinical trials by estimating transition rates for different risk groups.

[Socio-demographic and employment-related factors in the German National Cohort (GNC; NAKO Gesundheitsstudie)]. / Soziodemografische und erwerbsbezogene Merkmale in der NAKO Gesundheitsstudie.

BACKGROUND: In epidemiologic studies, standardised measurement of socio-demographic and employment-related factors is becoming increasingly important, as variables such as gender, age, education or employment status are factors influencing health and disease risks. AIMS: The article gives an overview of the scientific background and assessment of socio-demographic factors in the German National Cohort Study. In addition, the distribution of individual characteristics in the cohort as well as relationships with health-related measures are presented by way of example. MATERIAL AND METHODS: The analysis is based on the data of the first half of the baseline survey (n = 101,724). On this basis, we present the distribution of key socio-demographic characteristics and analyse relationships with exemplary selected health indicators (body mass index, self-reported health) to assess the validity of socio-demographic data measurements. RESULTS: On average, study participants were 52.0 years old (SD = 12.4). Of the participants, 53.6% were women, 54.3% had high education, 60.1% were married and 72% were employed while 3.4% were unemployed. Well-established correlations between socio-demographic factors and health could be reproduced with the German National Cohort data. For example, low education, old age and unemployment were associated with an increased prevalence of obesity and poor self-reported health. DISCUSSION: The German National Cohort provides a comprehensive measurement of socio-demographic characteristics. Combined with a wide range of health data and the longitudinal measurements available in the future, this opens up new opportunities for health science and social epidemiological research in Germany.

The association between unemployment and depression-Results from the population-based LIFE-adult-study.

BACKGROUND: Unemployment is a risk factor for impaired mental health. Based on a large population-based sample, in this study we therefore sought to provide detailed information on the association between unemployment and depression including information on (i) differences between men and women, (ii) differences between different types of unemployment, and (iii) on the impact of material and social resources on the association. METHODS: We studied 4,842 participants (18-65 years) of the population-based LIFE-Adult-Study. Depression was assessed using the Center for Epidemiological Studies Depression Scale. Employment status was divided into three groups: being employed, being unemployed receiving entitlement-based benefits, being unemployed receiving means-tested benefits. Multivariate logistic regression models were applied to assess the association between employment status and depression. RESULTS: Statistically significantly increased depression risk was solely found for unemployed persons receiving means-tested benefits. Adjusting for differences in sociodemographic factors, net personal income and risk of social isolation, comparable associations of being unemployed and receiving means-tested benefits with elevated depression risk were found for men (Odds Ratio/OR = 2.17, 95%-CI = 1.03-4.55) and women (OR = 1.98, 95%-CI:1.22-3.20). LIMITATIONS: No conclusions regarding causality can be drawn due to the cross-sectional study design. It was not possible to assess length of unemployment spells. CONCLUSION: Unemployed persons receiving means-tested benefits in Germany constitute a risk group for depression that needs specific attention in the health care and social security system. The negative impact of unemployment on depression risk cannot be explained solely by differences in material and social resources. Contrasting earlier results, women are equally affected as men.

Age-, sex-, and education-specific norms for an extended CERAD Neuropsychological Assessment Battery-Results from the population-based LIFE-Adult-Study.

OBJECTIVE: To provide new age-, sex-, and education-specific reference values for an extended version of the well-established Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) that additionally includes the Trail Making Test and the Verbal Fluency Test-S-Words. METHOD: Norms were calculated based on the cognitive performances of n = 1,888 dementia-free participants (60-79 years) from the population-based German LIFE-Adult-Study. Multiple regressions were used to examine the association of the CERAD-NAB scores with age, sex, and education. In order to calculate the norms, quantile and censored quantile regression analyses were performed estimating marginal means of the test scores at 2.28, 6.68, 10, 15.87, 25, 50, 75, and 90 percentiles for age-, sex-, and education-specific subgroups. RESULTS: Multiple regression analyses revealed that younger age was significantly associated with better cognitive performance in 15 CERAD-NAB measures and higher education with better cognitive performance in all 17 measures. Women performed significantly better than men in 12 measures and men than women in four measures. The determined norms indicate ceiling effects for the cognitive performances in the Boston Naming, Word List Recognition, Constructional Praxis Copying, and Constructional Praxis Recall tests. CONCLUSIONS: The new norms for the extended CERAD-NAB will be useful for evaluating dementia-free German-speaking adults in a broad variety of relevant cognitive domains. The extended CERAD-NAB follows more closely the criteria for the new DSM-5 Mild and Major Neurocognitive Disorder. Additionally, it could be further developed to include a test for social cognition. (PsycINFO Database Record

Body surface assessment with 3D laser-based anthropometry: reliability, validation, and improvement of empirical surface formulae.

PURPOSE: Body surface area is a physiological quantity relevant for many medical applications. In clinical practice, it is determined by empirical formulae. 3D laser-based anthropometry provides an easy and effective way to measure body surface area but is not ubiquitously available. We used data from laser-based anthropometry from a population-based study to assess validity of published and commonly used empirical formulae. METHODS: We performed a large population-based study on adults collecting classical anthropometric measurements and 3D body surface assessments (N = 1435). We determined reliability of the 3D body surface assessment and validity of 18 different empirical formulae proposed in the literature. The performance of these formulae is studied in subsets of sex and BMI. Finally, improvements of parameter settings of formulae and adjustments for sex and BMI were considered. RESULTS: 3D body surface measurements show excellent intra- and inter-rater reliability of 0.998 (overall concordance correlation coefficient, OCCC was used as measure of agreement). Empirical formulae of Fujimoto and Watanabe, Shuter and Aslani and Sendroy and Cecchini performed best with excellent concordance with OCCC > 0.949 even in subgroups of sex and BMI. Re-parametrization of formulae and adjustment for sex and BMI slightly improved results. CONCLUSION: In adults, 3D laser-based body surface assessment is a reliable alternative to estimation by empirical formulae. However, there are empirical formulae showing excellent results even in subgroups of sex and BMI with only little room for improvement.

The Speaking Voice in the General Population: Normative Data and Associations to Sociodemographic and Lifestyle Factors.

OBJECTIVES: Normative data concerning the speaking voice in the general population were gathered with the aim to establish standard values for clinical diagnostics. Associations between the speaking voice and sociodemographic factors were examined. STUDY DESIGN: This is a prospective cross-sectional population-based study. METHODS: Speaking voice profiles were measured for 2472 (1154 male and 1318 female) participants between the ages of 40 and 79 years, using four speaking voice intensity levels: softest speaking voice (I), conversational voice (II), classroom voice (III), and shouting voice (IV). Smoking status and socioeconomic status were assessed. Data were analyzed using multivariate regression. RESULTS: The mean voice frequencies were 111.8 Hz for male and 161.3 Hz for female participants (I), 111.9 Hz for male and 168.5 Hz for female participants (II), 130.2 Hz for male and 198.0 Hz for female participants (III), and 175.5 Hz for male and 246.2 Hz for female participants (IV). Frequencies increased significantly with age for male but not for female participants. Sound pressure levels rose significantly with age at intensity levels I-III for both sexes, but decreased at intensity level IV. Frequencies and sound pressure levels were similar between nonsmokers and former smokers. Current smokers showed significantly lower frequencies as opposed to non- and former smokers. Speaking voice range and dynamics increased with higher socioeconomic status. CONCLUSIONS: The data are suitable as age-adjusted normative values for clinical measurement of the speaking voice. The mean fundamental speaking voice frequency of female participants was six to seven semitones lower than previously described.

The LIFE-Adult-Study: objectives and design of a population-based cohort study with 10,000 deeply phenotyped adults in Germany.

BACKGROUND: The LIFE-Adult-Study is a population-based cohort study, which has recently completed the baseline examination of 10,000 randomly selected participants from Leipzig, a major city with 550,000 inhabitants in the east of Germany. It is the first study of this kind and size in an urban population in the eastern part of Germany. The study is conducted by the Leipzig Research Centre for Civilization Diseases (LIFE). Our objective is to investigate prevalences, early onset markers, genetic predispositions, and the role of lifestyle factors of major civilization diseases, with primary focus on metabolic and vascular diseases, heart function, cognitive impairment, brain function, depression, sleep disorders and vigilance dysregulation, retinal and optic nerve degeneration, and allergies. METHODS/DESIGN: The study covers a main age range from 40-79 years with particular deep phenotyping in elderly participants above the age of 60. The baseline examination was conducted from August 2011 to November 2014. All participants underwent an extensive core assessment programme (5-6 h) including structured interviews, questionnaires, physical examinations, and biospecimen collection. Participants over 60 underwent two additional assessment programmes (3-4 h each) on two separate visits including deeper cognitive testing, brain magnetic resonance imaging, diagnostic interviews for depression, and electroencephalography. DISCUSSION: The participation rate was 33 %. The assessment programme was accepted well and completely passed by almost all participants. Biomarker analyses have already been performed in all participants. Genotype, transcriptome and metabolome analyses have been conducted in subgroups. The first follow-up examination will commence in 2016.

Assessment and prognostic significance of the epidermal growth factor receptor vIII mutation in glioblastoma patients treated with concurrent and adjuvant temozolomide radiochemotherapy.

The epidermal growth factor receptor vIII mutant (EGFRvIII) is found in ~50% of all EGFR-amplified glioblastomas and constitutes a tumor-specific therapeutic target. To assess molecular testing approaches and the prognostic role of EGFRvIII in patients treated according to current standards of care, we compared different EGFRvIII detection methods and correlated EGFRvIII status with outcome in a prospective patient cohort of the German Glioma Network. In total, 184 newly diagnosed glioblastoma patients were investigated for EGFR amplification and for expression of EGFR and EGFRvIII by immunohistochemistry. Further, the EGFRvIII status was additionally studied by multiplex ligation-dependent probe amplification (MLPA) analysis and reverse transcription-PCR (RT-PCR). Immunohistochemistry demonstrated EGFRvIII in 34 of 184 patients (18%). RT-PCR or MLPA analysis detected four additional EGFRvIII-positive patients. Overall, RT-PCR and immunohistochemistry were more sensitive for EGFRvIII detection than MLPA. EGFRvIII status was not associated with progression-free and overall survival. EGFRvIII also had no prognostic significance in the subgroup of patients who were free from progression after concomitant radiochemotherapy and thus would be eligible for the ongoing ACT IV EGFRvIII vaccination trial. Age, extent of resection and O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status appeared to be less prognostic in EGFRvIII-positive patients. Thus, EGFRvIII positivity is not a major negative prognostic factor in glioblastoma patients treated according to current standards of care. Data from phase II EGFRvIII-targeted vaccination trials compare favorably with the present contemporary results, supporting the further exploration of EGVRvIII vaccination in newly diagnosed glioblastoma.

Validity, intra- and inter-observer reliability of automated devices for the assessment of ankle brachial index using photo-plethysmography.

BACKGROUND: Ankle-brachial-Index (ABI) measured by manual Dopplersonography is an easily assessable marker of global cardiovascular risk. The aim of this study was to establish novel photo-plethysmography (PPG)-based ABI assessments in an epidemiologic context and to compare its results with those of Doppler. METHODS: Two devices for PPG-based ABI assessments (Vicorder, Vascular Explorer) were tested and compared against Doppler in 56 putatively healthy subjects. We determined acceptance, time requirements, agreement of repeat measurements, agreement with Doppler and intra- and inter-observer concordances for both devices and compared the results. Differences between cuff inflation- and deflation-based methods were also studied for Vascular Explorer. RESULTS: Acceptance was similar for both devices but Vascular Explorer was more time consuming. Agreement of multiple measurements was moderate for both methods highlighting the importance of measurement replicates. Both automated devices showed significantly higher ABI compared to Doppler which can be traced back to higher brachial pressures (Vicorder) or higher ankle pressures (Vascular Explorer). This effect is more pronounced for Vascular Explorer but can be ameliorated using the deflation method of measurement. Intra-observer concordances were similar. Inter-observer concordance was non-significantly better for Vicorder. CONCLUSIONS: Both devices proved to be feasible in epidemiologic studies, but compared to Doppler, do not constitute an advantage regarding time requirement and accuracy of ABI assessment. Since PPG-based ABI values are inflated compared to Doppler, it will be necessary to adjust Doppler-based cut-offs for risk stratification.

Mode of action and effects of standardized collaborative disease management on mortality and morbidity in patients with systolic heart failure: the Interdisciplinary Network for Heart Failure (INH) study.

BACKGROUND: Trials investigating efficacy of disease management programs (DMP) in heart failure reported contradictory results. Features rendering specific interventions successful are often ill defined. We evaluated the mode of action and effects of a nurse-coordinated DMP (HeartNetCare-HF, HNC). METHODS AND RESULTS: Patients hospitalized for systolic heart failure were randomly assigned to HNC or usual care (UC). Besides telephone-based monitoring and education, HNC addressed individual problems raised by patients, pursued networking of health care providers and provided training for caregivers. End points were time to death or rehospitalization (combined primary), heart failure symptoms, and quality of life (SF-36). Of 1007 consecutive patients, 715 were randomly assigned (HNC: n=352; UC: n=363; age, 69±12 years; 29% female; 40% New York Heart Association class III-IV). Within 180 days, 130 HNC and 137 UC patients reached the primary end point (hazard ratio, 1.02; 95% confidence interval, 0.81-1.30; P=0.89), since more HNC patients were readmitted. Overall, 32 HNC and 52 UC patients died (1 UC patient and 4 HNC patients after dropout); thus, uncensored hazard ratio was 0.62 (0.40-0.96; P=0.03). HNC patients improved more regarding New York Heart Association class (P=0.05), physical functioning (P=0.03), and physical health component (P=0.03). Except for HNC, health care utilization was comparable between groups. However, HNC patients requested counseling for noncardiac problems even more frequently than for cardiovascular or heart-failure-related issues. CONCLUSIONS: The primary end point of this study was neutral. However, mortality risk and surrogates of well-being improved significantly. Quantitative assessment of patient requirements suggested that besides (tele)monitoring individualized care considering also noncardiac problems should be integrated in efforts to achieve more sustainable improvement in heart failure outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN23325295.

Noninvasive assessment of pediatric inflammatory bowel disease with ¹8F-fluorodeoxyglucose-positron emission tomography and computed tomography.

OBJECTIVES: ¹8F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a less invasive diagnostic tool and promising in detecting gastrointestinal lesions of pediatric inflammatory bowel disease (IBD) patients. Co-registration of low-dose computed tomography (CT) could lead to improvements in the assessment of disease. Therefore, this retrospective study evaluates the value of PET±CT in pediatric IBD patients. PATIENTS AND METHODS: We analyzed ¹8F-FDG-PET scans without (n=24) or with combined (n=21) low-dose CT in children (18 females, 27 males, age: 3.7-16.7 years, median 13.2 years) who presented with the diagnosis of IBD (n=45). Results of PET±CT scans and conventional diagnostic procedures (endoscopy, histology, and ultrasound) were compared by a segment-based analysis. RESULTS: Overall, 253 segments of the gastrointestinal tract (GIT) were explored by endoscopy/histology and ¹8F-FDG-PET±CT. Twenty-five additional small bowel segments were assessed by abdominal ultrasound and further 152 GIT segments not reached during endoscopy were evaluated by PET±CT. PET±CT revealed a segment-based sensitivity, specificity, positive predictive value, negative predictive value, and an accuracy for the detection of GIT lesions of 82, 97, 96, 88, and 91%, respectively. The patient-based sensitivity and specificity was 97 and 100%, respectively. Interestingly, the co-registration of CT did not improve the diagnostic informative value. CONCLUSION: FDG-PET±CT is especially suitable for the assessment of IBD in children. The radiation exposure of 3-7 mSv is justified by the accuracy of this approach. FDG-PET seems to be a reliable tool for detecting inflamed gut segments in IBD with high sensitivity and specificity. The co-registration of CT had no additional benefit.

Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era.

PURPOSE: The International Prognostic Index (IPI) is widely used for risk stratification of patients with aggressive B-cell lymphoma. The introduction of rituximab has markedly improved outcome, and R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) has become the standard treatment for CD20(+) diffuse large B-cell lymphoma. To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP, we analyzed the prognostic relevance of IPI in three prospective clinical trials. PATIENTS AND METHODS: In total, 1,062 patients treated with rituximab were included (MabThera International Trial [MInT], 380 patients; dose-escalated regimen of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (MegaCHOEP) trial, 72 patients; CHOP + rituximab for patients older than age 60 years [RICOVER-60] trial, 610 patients). A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free, progression-free, and overall survival. RESULTS: IPI score was significant for all three end points. Rituximab significantly improved treatment outcome within each IPI group resulting in a quenching of the Kaplan-Meier estimators. However, IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid. The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP. CONCLUSION: The effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy. These results demonstrate that the IPI is still valid in the R-CHOP era.

Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy.

A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas.