Institute of Epidemiology II


Institute of Epidemiology II

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Lukaschek K.,Institute of Epidemiology II | Baumert J.,Institute of Epidemiology II | Forstl H.,TU Munich | Ladwig K.-H.,Institute of Epidemiology II | Ladwig K.-H.,TU Munich
British Journal of Psychiatry | Year: 2014

Background: Suicide prediction during psychiatric in-patient treatment remains an unresolved challenge. Aims: To identify determinants of railway suicides in individuals receiving in-patient psychiatric treatment. Method: The study population was drawn from patients admitted to six psychiatric hospitals in Germany during a 10-year period (1997-2006). Data from 101 railway suicide cases were compared with a control group of 101 discharged patients matched for age, gender and diagnosis. Results: Predictors of suicide were change of therapist (OR = 22.86, P = 0.004), suicidal ideation (OR = 7.92, P50.001), negative or unchanged therapeutic course (OR = 7.73, P50.001), need of polypharmaceutical treatment (OR = 2.81, P = 0.04) and unemployment (OR = 2.72, P = 0.04). Neither restlessness nor impulsivity predicted in-patient suicide. Conclusions: Suicidal ideation, unfavourable clinical course and the use of multiple psychotropic substances (reflecting the severity of illness) were strong determinants of railway suicides. The most salient finding was the vital impact of a change of therapist. These findings deserve integration into the clinical management of patients with serious mental disease.

Andre R.,Toulouse University Hospital Center | Bongard V.,University Paul Sabatier | Elosua R.,Municipal Institute of Health Assistance Municipal Institute of Medical Research IMAS IMIM | Elosua R.,CIBER ISCIII | And 17 more authors.
Heart | Year: 2014

Objective We aimed to describe current characteristics of patients admitted for acute coronary syndrome (ACS) in Western Europe and to analyse whether international in-hospital mortality variations are explained by differences in patients' baseline characteristics and in clinical management. Methods We studied a population-based longitudinal cohort conducted in Finland, France, Germany, Greece, Portugal and Spain, and comprising 12 231 consecutive ACS patients admitted in 53 hospitals between 2008 and 2010. Baseline characteristics, clinical management and inhospital outcomes were recorded. Contextual effect of country on death was analysed through multilevel analysis. Results Of all patients included, 8221 (67.2%) had NSTEMI (non-ST-elevation myocardial infarction), and 4010 (32.8%) had STEMI (ST-elevation myocardial infarction). Inhospital mortality ranged from 15.1% to 4.9% for German and Spanish STEMI patients, and from 6.8% to 1.9% for Finnish and French NSTEMI patients (p<0.001 for both). These international variations were explained by differences in patients' baseline characteristics (older patients more likely to have cardiogenic shock in Germany) and in clinical management, with differences in rates of thrombolysis (less performed in Germany) and primary percutaneous coronary intervention (high in Germany, low in Greece). A remaining contextual effect of country was identified after extensive adjustment. Conclusions Inhospital mortality rates of STEMI and NSTEMI patients were two to three times higher in Finland, Germany and Portugal than in Greece and Spain, with intermediate values for France. Differences in baseline characteristics and clinical management partly explain differences in outcome. Our data also suggest an impact of the healthcare system organisation.

News Article | December 7, 2016

According to the authors headed by Dr. Hildegard Seidl from the Institute of Health Economics and Health Care Management (IGM) and Dr. Inge Kirchberger from the Institute of Epidemiology II (EPI II), regular contact and information programs provided by trained nurses additionally produce further positive effects: improved muscle strength and blood fat levels with less significant physical restrictions and healthier diets of the patients. The results are based on the evaluation of data from the KORINNA study, in which the scientists examined more than 300 cardiac infarction patients aged 65 years or older. After being discharged from the hospital, the patients were randomly divided into two groups. One group received the customary treatment in accordance with German standards, while the other additionally received so-called case management support from appropriately trained nurses. This included such measures as informative material at the time of the hospital discharge, home visits, and regular telephone contact (at least every three months). First author Seidl explains the hypothesis: "We wanted to test whether or not the greater information density on topics such as medication intake, nutrition, and psychosocial aspects, combined with instructions on the measurement of important parameters such as blood pressure, pulse or blood sugar levels in patients, leads to improved quality of life. Because according to the authors, older patients with myocardial infarction frequently suffer from concurrent conditions that can lead to multiple medications, reduced quality of life, and readmission to the hospital. In Germany, however, until now no case management program has been offered and evaluated for elderly patients with myocardial infarction. "Our health care system faces constantly increasing costs due to demographic developments and expensive innovations," reports study leader Prof. Dr. Rolf Holle. "Cost-effective solutions that improve the patients' health are more necessary than ever," the IGM deputy director states. It is therefore useful to see if the results that have now been published should also lead to possible treatment recommendations. "The study that we conducted creates a good information basis that the relevant healthcare policy authorities can use to make rational decisions," Seidl explains. "The results provide scientific evidence that supplementary care in a case management program can cost-effectively improve the health of elderly patients. It is worth considering adding a cardiac infarction diagnosis to the guideline for transferring a physician's activities to a nursing staff* in order to allow case management for this patient group." Myocardial infarction is one of the leading causes of death around the world. Patients who have already suffered a cardiac infarction have a high risk for a renewed heart attack, but this risk can be reduced if the patient makes certain life style changes and reliably takes the prescribed medication. These changes are facilitated by close and continuing contact with therapists, and this contact can be promoted by low-threshold programs. * This specifically refers to the guideline pursuant to Section 63 Par. 3c SGB V [German code of social law]. The KORINNA Study: Health economic evaluation of a case management program in elderly coronary infarction patients. In the monocentric study, 340 patients aged 65 years or more with acute myocardial infarction were recruited in the Central Hospital of Augsburg and randomly assigned to either the intervention or the control group. Patients in the intervention group received one home visit, or more if necessary, by trained personnel over a period of three years, as well as quarterly telephone consultations, while participants in the control group received the customary care. The state of health and the utilization of health services in both groups were polled every three months by telephone. The primary target criterion was the time from discharge from the base stay until the first unplanned readmission (or until death outside of the hospital). Secondary target criteria, such as clinical measurement parameters, functional capability, depressive tendencies, and health-related quality of life, were collected during the examination after three years. Costs of the hospitalizations were determined from the administrative data, while all other costs were estimated according to the unit cost approach on the basis of information provided by the patients. Further information is available at: http://www. Prof. Dr. Christa Meisinger (EPI II, MONICA/KORA Herzinfarktregister, NAKO Study Center), Prof. Dr. Bernhard Kuch (now chief physician at Stiftungskrankenhaus Nördlingen) and Prof. Dr. Rolf Holle (IGM) planned the study, which was performed at the Central Hospital of Augsburg. Data analysis was performed at IGM by Dr. Hildegard Seidl, Dr. Matthias Hunger und Dr. Björn Stollenwerk. The case management program offered for elderly patients did not show any statistically verifiable improvement in the quality of life in the first survey within the first follow-up year. Follow-up in the framework of the study was extended to three years in order to allow an additional analysis of the medium-term effects. This is where the current study comes in. No evidence could be provided for a longer time to the first readmission to the hospital or to death (combined endpoint) or for a gain in quality-adjusted years of life. Seidl, H. et al. (2016): The 3-year cost-effectiveness of a nurse-based case management versus usual care for elderly patients with myocardial infarction: Results from the KORINNA follow-up study. Value in Health, doi: 10.1016/j.jval.2016.10.001 Kirchberger, I. et al (2015): Effects of a 3-Year Nurse-Based Case Management in Aged Patients with Acute Myocardial In-farction on Rehospitalisation, Mortality, Risk Factors, Physical Functioning and Mental Health. A Secondary Analysis of the Randomized Controlled KORINNA Study. PLoS One, doi: 10.1371/journal.pone.0116693. The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www. The Institute of Health Economics and Health Care Management (IGM) examines approaches to improving the effectiveness and efficiency of health care. The health care system faces the challenge of delivering high-quality, economically viable medical services to meet the needs of the population. Rapid advances in medical technology and fast-changing demographics further aggravate this problem. A firmly based evaluation of the effectiveness and efficiency of health care structures and processes is therefore an essential prerequisite for a rational health care policy. http://www. The Institute of Epidemiology II (EPI II) focuses on the assessment of environmental and lifestyle risk factors which jointly affect major chronic diseases such as diabetes, heart disease and mental health. Research builds on the unique resources of the KORA cohort, the KORA myocardial infarction registry, and the KORA aerosol measurement station. Aging-related phenotypes have been added to the KORA research portfolio within the frame of the Research Consortium KORA-Age. The institute's contributions are specifically relevant for the population as modifiable personal risk factors are being researched that could be influenced by the individual or by improving legislation for the protection of public health. http://www. For almost 30 years, the Cooperative Health Research in the Region of Augsburg (KORA) has been examining the health of thousands of citizens in Augsburg and environs. The aim of the project is to increase understanding of the impact of environmental factors, behaviour and genes on human health. The KORA studies focus on matters relating to the development and progression of chronic diseases, in particular myocardial infarction and diabetes mellitus. To that end, research is conducted into risk factors arising from lifestyle factors (including smoking, diet and exercise), environmental factors (including air pollution and noise) and genetics. Questions relating to the use and cost of health services are examined from the point of view of health services research. http://www. Dr. Hildegard Seidl, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute of Health Economics and Health Care Management, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 4485 - E-mail:

Petersen A.-K.,Institute of Genetic Epidemiology | Zeilinger S.,Research Unit of Molecular Epidemiology | Kastenmuller G.,Institute of Bioinformatics and Systems Biology | Werner R.-M.,Institute of Bioinformatics and Systems Biology | And 20 more authors.
Human Molecular Genetics | Year: 2014

Previously,we reported strong influences of genetic variants on metabolic phenotypes, some of them with clinical relevance. Here, we hypothesize that DNA methylation may have an important and potentially independent effect on human metabolism. Totest this hypothesis,we conducted what is to the best of our knowledge the first epigenome-wide association study (EWAS) between DNA methylation and metabolic traits (metabotypes) in human blood. We assess 649 blood metabolic traits from 1814 participants of the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) population study for association with methylation of 457 004 CpG sites, determined on the Infinium Human Methylation 450 Bead Chip platform. Using the EWAS approach, we identified two types of methylome-metabotype associations. One type is driven by an underlying genetic effect; the other type is independent of genetic variation and potentially driven by common environmental and life-style-dependent factors. We report eight CpG loci atgenome-wide significance that have a genetic variant as confounder (P = 3.9 × 10-20 to 2.0 × 10-108, r2 = 0.036 to 0.221).Seven loci display CpG site-specific associations to metabotypes ,but do not exhibit any underlying genetic signals (P = 9.2 × 10-14 to 2.7 × 10-27, r2 = 0.008 to 0.107). We further identify several groups of CpG loci that associate with a same metabotype, such as 4-vinylphenol sulfate and 4-androsten-3-beta,17-beta-diol disulfate. In these cases, the association between CpG-methylation and metabotype is likely the result of a common external environmental factor, including smoking. Our study shows that analysis of EWAS with large numbers of metabolic traits in large population cohorts are, in principle, feasible. Taken together, our data suggest that DNA methylation plays an important role in regulating human metabolism. © The Author 2013. Published by Oxford University Press.

PubMed | Institute of Bioinformatics and Systems Biology and and Institute of Epidemiology II
Type: Journal Article | Journal: International journal of epidemiology | Year: 2016

Short-term exposure to air pollution is associated with morbidity and mortality. Metabolites are intermediaries in biochemical processes, and associations between air pollution and metabolites can yield unique mechanistic insights.We used independent cross-sectional samples with targeted metabolomics (138 metabolites across five metabolite classes) from three cohort studies, each a part of the Cooperative Health Research in the Region of Augsburg (KORA). The KORA cohorts are numbered (1 to 4) according to which survey they belong to, and lettered S or F according to whether the survey was a baseline or follow-up survey. KORA F4 (N=3044) served as our discovery cohort, with KORA S4 (N=485) serving as the primary replication cohort. KORA F4 and KORA S4 were primarily fasting cohorts. We used the non-fasting KORA F3 (N=377) cohort to evaluate replicated associations in non-fasting individuals, and we performed a random effects meta-analysis of all three cohorts. Associations between the 0-4-day lags and the 5-day average of particulate matter (PM)There were 10 discovery cohort associations, of which seven were lysophosphatidylcholines (LPCs); NOLPCs are associated with short-term exposure to air pollutants, in particular NO

News Article | September 13, 2016

A new study performed by researchers at Helmholtz Zentrum München, in collaboration with researchers at the German Center for Diabetes Research, has revealed that common levels of air pollution in homes notably increase the risk of developing insulin resistance as a pre-diabetic state of type 2 diabetes. What this means is that risk is strongly associated not just with “lifestyle” and genetics, but also with the environmental factors that most people have no control over, but which governments have the ability to regulate. Notably, the levels of air pollution observed in the study (in Germany) are well within European Union limits, but above those proposed by the World Health Organization (WHO). “Whether the disease becomes manifest and when this occurs is not only due to lifestyle or genetic factors, but also due to traffic-related air pollution,” commented Professor Annette Peters, director of the Institute of Epidemiology II at Helmholtz Zentrum München and head of the research area of epidemiology of the DZD. The press release continues, noting that, in collaboration with German Diabetes Center Düsseldorf and the German Heart Centre, the researchers “analyzed the data of nearly 3,000 participants of the KORA study who live in the city of Augsburg and two adjacent rural counties. All individuals were interviewed and physically examined. Furthermore, the researchers took fasting blood samples, in which they determined various markers for insulin resistance and inflammation. In addition, leptin was examined as adipokine which has been suggested to be associated with insulin resistance. Non-diabetic individuals underwent an oral glucose tolerance test to detect whether their glucose metabolism was impaired. The researchers compared these data with the concentrations of air pollutants at the place of residence of the participants, which they estimated using predictive models based on repeated measurements at 20 sites (for particle measurements) and at 40 sites (for nitrogen dioxide measurements) in the city and in the rural counties.” “The results revealed that people who already have an impaired glucose metabolism, so-called pre-diabetic individuals, are particularly vulnerable to the effects of air pollution,” stated Dr Kathrin Wolf, lead author of the new study. “In these individuals, the association between increases in their blood marker levels and increases in air pollutant concentrations is particularly significant! Thus, over the long term — especially for people with impaired glucose metabolism — air pollution is a risk factor for type 2 diabetes.” With regard to the implications of the findings, researcher Dr Alexandra Schneider, noted: “Lowering the threshold for acceptable air pollution levels would be a prudent step. We are all exposed to air pollution. An individual reduction by moving away from highly polluted areas is rarely an option.” The new findings are detailed in a paper published in the journal Diabetes.   Drive an electric car? Complete one of our short surveys for our next electric car report.   Keep up to date with all the hottest cleantech news by subscribing to our (free) cleantech newsletter, or keep an eye on sector-specific news by getting our (also free) solar energy newsletter, electric vehicle newsletter, or wind energy newsletter.  

News Article | September 8, 2016

« Civil Maps debuts augmented reality maps for self-driving cars | Main | KLM to operate biofuel flights out of Los Angeles » Exposure to air pollution increases the risk of developing insulin resistance as a pre-diabetic state of type 2 diabetes, according to a new study by scientists of Helmholtz Zentrum München, in collaboration with colleagues of the German Center for Diabetes Research (DZD). The researchers reported these results in the journal Diabetes. Whether diabetes becomes manifest and when this occurs is not only due to lifestyle or genetic factors, but also due to traffic-related air pollution, said Professor Annette Peters, director of the Institute of Epidemiology II at Helmholtz Zentrum München and head of the research area of epidemiology of the DZD. For the current study, the team analyzed the data of 2,944 participants of the KORA (Cooperative Health Research in the Region Augsburg) F4 study conducted in southern Germany (2006-2008). They analyzed associations between individual air pollution concentration estimated by land use regression and HOMA-IR (homeostasis model assessment-estimated insulin resistance), glucose, insulin, HbA (glycated hemoglobin), leptin, and hs-CRP (high-sensitivity C-reactive protein) from fasting samples using multivariable linear regression models. Effect estimates were calculated for the whole study population and subgroups of non-diabetic, pre-diabetic and diabetic individuals. Among all participants, a 7.9μg/m3 increment in particulate matter Nitrogen dioxide was associated with HOMA-IR, glucose, insulin, and leptin. Effect estimates for pre-diabetic individuals were much larger and highly statistically significant, while non-diabetic and diabetic individuals showed rather weak associations. No association was seen for HbA . The results revealed that people who already have an impaired glucose metabolism, so-called pre-diabetic individuals, are particularly vulnerable to the effects of air pollution. In these individuals, the association between increases in their blood marker levels and increases in air pollutant concentrations is particularly significant! Thus, over the long term—especially for people with impaired glucose metabolism—air pollution is a risk factor for type 2 diabetes. The authors are also concerned that the concentrations of air pollutants, though below EU threshold values, are still above the proposed guidelines of the World Health Organization (WHO). As a consequence, they demand changes in government policy. Moreover, the association between increased exposure to air pollution and respiratory and cardiovascular diseases has now been clearly established. Next, the scientists want to investigate the influence of ultrafine particles. A previous study of Helmholtz Zentrum München from 2013 showed that ultrafine particulate air pollution increases the risk of insulin resistance in childhood. In a meta-analysis from 2015 the same authors concluded that there is an association between long-term exposure to air pollutants and the development of type 2 diabetes.

Zech M.,Klinikum rechts der IsarTechnical University MunchenMunich Germany | Castrop F.,Neurologische Klinik und Poliklinik | Schormair B.,Klinikum rechts der IsarTechnical Universityt MunchenMunich Germany | Jochim A.,Neurologische Klinik und Poliklinik | And 10 more authors.
Movement Disorders | Year: 2014

Recessive DYT16 dystonia associated with mutations in PRKRA has until now been reported only in seven Brazilian patients. The aim of this study was to elucidate the genetic cause underlying disease in a Polish family with autosomal-recessive, early-onset generalized dystonia and slight parkinsonism, and to explore further the role of PRKRA in a dystonia series of European ancestry. We employed whole-exome sequencing in two affected siblings of the Polish family and filtered for rare homozygous and compound heterozygous variants shared by both exomes. Validation of the identified variants as well as homozygosity screening and copy number variation analysis was carried out in the two affected individuals and their healthy siblings. PRKRA was analyzed in 339 German patients with various forms of dystonia and 376 population-based controls by direct sequencing or high-resolution melting. The previously described homozygous p.Pro222Leu mutation in PRKRA was found to segregate with the disease in the studied family, contained in a 1.2 Mb homozygous region identical by state with all Brazilian patients in chromosome 2q31.2. The clinical presentation with young-onset, progressive generalized dystonia and mild parkinsonism resembled the phenotype of the original DYT16 cases. PRKRA mutational screening in additional dystonia samples revealed three novel heterozygous changes (p.Thr34Ser, p.Asn102Ser, c.-14A>G), each in a single subject with focal/segmental dystonia. Our study provides the first independent replication of the DYT16 locus at 2q31.2 and strongly confirms the causal contribution of the PRKRA gene to DYT16. Our data suggest worldwide involvement of PRKRA in dystonia. © 2014 International Parkinson and Movement Disorder Society.

PubMed | Institute of Health Economics and Health Care Management, Innsbruck Medical University, Ludwig Maximilians University of Munich, University of Tromsø and 3 more.
Type: Journal Article | Journal: BMC geriatrics | Year: 2016

Reduced muscular strength in the old age is strongly related to activity impairment and mortality. However, studies evaluating the gender-specific association between muscularity and mortality among older adults are lacking. Thus, the objective of the present study was to examine gender differences in the association between muscular strength and mortality in a prospective population-based cohort study.Data used in this study derived from the Cooperative Health Research in the Region of Augsburg (KORA)-Age Study. The present analysis includes 1,066 individuals (mean age 7611 SD years) followed up over 3years. Handgrip strength was measured using the Jamar Dynamometer. A Cox proportional hazard model was used to determine adjusted hazard ratios of mortality with 95% confidence intervals (95% CI) for handgrip strength. Potential confounders (i.e. age, nutritional status, number of prescribed drugs, diseases and level of physical activity) were pre-selected according to evidence-based information.During the follow-up period, 56 men (11%) and 39 women (7%) died. Age-adjusted mortality rates per 1,000 person years (95% CI) were 77 (59-106), 24 (13-41) and 14 (7-30) for men and 57 (39-81), 14 (7-27) and 1 (0-19) for women for the first, second and third sex-specific tertile of muscular strength, respectively. Low handgrip strength was significantly associated with all-cause mortality among older men and women from the general population after controlling for significant confounders. Hazard ratios (95% CI) comparing the first and second tertile to the third tertle were 3.33 (1.53-7.22) and 1.42 (0.61-3.28), respectively. Respective hazard ratios (95% CI) for mortality were higher in women than in men ((5.23 (0.67-40.91) and 2.17 (0.27-17.68) versus 2.36 (0.97-5.75) and 0.97 (0.36-2.57)).Grip strength is inversely associated with mortality risk in older adults, and this association is independent of age, nutritional status, number of prescribed drugs, number of chronic diseases and level of physical activity. The association between muscular strength and all-cause mortality tended to be stronger in women. It seems to be particularly important for the weakest to enhance their levels of muscular strength in order to reduce the risk of dying early.

Teumer A.,University of Greifswald | Rawal R.,Institute of Epidemiology | Homuth G.,University of Greifswald | Ernst F.,University of Greifswald | And 16 more authors.
American Journal of Human Genetics | Year: 2011

Thyroid disorders such as goiters represent important diseases, especially in iodine-deficient areas. Sibling studies have demonstrated that genetic factors substantially contribute to the interindividual variation of thyroid volume. We performed a genome-wide association study of this phenotype by analyzing a discovery cohort consisting of 3620 participants of the Study of Health in Pomerania (SHIP). Four genetic loci were associated with thyroid volume on a genome-wide level of significance. Of these, two independent loci are located upstream of and within CAPZB, which encodes the β subunit of the barbed-end F-actin binding protein that modulates actin polymerization, a process crucial in the colloid engulfment during thyroglobulin mobilization in the thyroid. The third locus marks FGF7, which encodes fibroblast growth factor 7. Members of this protein family have been discussed as putative signal molecules involved in the regulation of thyroid development. The fourth locus represents a "gene desert" on chromosome 16q23, located directly downstream of the predicted coding sequence LOC440389, which, however, had already been removed from the NCBI database as a result of the standard genome annotation processing at the time that this study was initiated. Experimental proof of the formerly predicted mature mRNA, however, demonstrates that LOC440389 indeed represents a real gene. All four associations were replicated in an independent sample of 1290 participants of the KORA study. These results increase the knowledge about genetic factors and physiological mechanisms influencing thyroid volume. © 2011 The American Society of Human Genetics.

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