• [Assessment of self-reported cardiovascular and metabolic diseases in the German National Cohort (GNC, NAKO Gesundheitsstudie): methods and initial results].

      Jaeschke, Lina; Steinbrecher, Astrid; Greiser, Karin Halina; Dörr, Marcus; Buck, Thomas; Linseisen, Jakob; Meisinger, Christa; Ahrens, Wolfgang; Becher, Heiko; Berger, Klaus; et al. (Springer, 2020-03-10)
      BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.
    • [Occurrence of bronchial asthma and age at initial asthma diagnosis-first results of the German National Cohort].

      Langer, Susan; Horn, Johannes; Kluttig, Alexander; Mikolajczyk, Rafael; Karrasch, Stefan; Schulz, Holger; Wichmann, Heinz-Erich; Linseisen, Jakob; Jaeschke, Lina; Pischon, Tobias; et al. (Springer, 2020-03-03)
      BACKGROUND: Asthma is one of the most common chronic diseases in both children and adults. Asthma first occurring in adulthood (adult-onset asthma, AOA) is associated with poorer prognosis compared to childhood-onset asthma (COA), which urgently calls for more research in this area. The aim of this work was to analyze the data on asthma collected in the German National Cohort and compare it with the German Health Interview and Examination Survey for Adults (DEGS), in particular regarding AOA. MATERIAL AND METHODS: Our analysis was based on the dataset of the main questionnaire at mid-term of the German National Cohort baseline examination, comprising 101,723 participants. Variables considered in the analyses were self-reported diagnosis of asthma, age at first diagnosis, asthma treatment in the past 12 months, age, and sex. RESULTS: In the midterm dataset, 8.7% of women and 7.0% of men in the German National Cohort reported that they had ever been diagnosed with asthma. Approximately one third of participants with asthma received their initial diagnosis before their 18th birthday. COA affected 2.2% of women and 2.8% of men, whereas AOA affected 6.5% of women and 4.2% of men. During the previous 12 months, 33% of COA cases and 60% of AOA cases were medically treated. CONCLUSION: The proportion of persons affected by asthma in the German National Cohort, as well as observed patterns regarding age and gender, corresponds to other data sources such as DEGS. However, in our analysis, the proportion of individuals with AOA was higher than described in the literature. The increase in cumulative asthma diagnoses with age is markedly steeper in younger participants, indicating a rising trend over time.
    • [Lung function in the German National Cohort: methods and initial results].

      Karrasch, Stefan; Peters, Annette; Meisinger, Christa; Ferland, Maike; Jaeschke, Lina; Pischon, Tobias; Fricke, Julia; Keil, Thomas; Gastell, Sylvia; Schulze, Matthias; et al. (Springer Open choice, 2020-03-01)
      In the present dataset (n = 101,734), spirometry was available for 86,893 study participants and FeNO was available for 15,228 participants. The average (±SD) FEV1 Z score (according to GLI 2012) was -0.321 ± 1.047, the FVC Z score was -0.153 ± 0.941, and the FEV1/FVC Z score was -0.337 ± 0.901. The difference in FEV1/FVC between current smokers and never-smokers increased with age. The average FeNO was 14.2 ÷ 2.0 ppb. Current smoking reduced FeNO levels by 43%, whereas respiratory allergy increased FeNO levels by 16% in nonsmokers.
    • [Measuring physical fitness in the German National Cohort-methods, quality assurance, and first descriptive results].

      Kluttig, Alexander; Zschocke, Johannes; Haerting, Johannes; Schmermund, Axel; Gastell, Sylvia; Steindorf, Karen; Herbolsheimer, Florian; Hillreiner, Andrea; Jochem, Carmen; Baumeister, Sebastian; et al. (Springer Nature, 2020-03-01)
      Physical fitness is defined as an individual's ability to be physically active. The main components are cardiorespiratory fitness (CRF), muscle strength, and flexibility. Regardless of physical activity level, physical fitness is an important determinant of morbidity and mortality.The aim of the current study was to describe the physical fitness assessment methodology in the German National Cohort (NAKO) and to present initial descriptive results in a subsample of the cohort.In the NAKO, hand grip strength (GS) and CRF as physical fitness components were assessed at baseline using a hand dynamometer and a submaximal bicycle ergometer test, respectively. Maximum oxygen uptake (VO2max) was estimated as a result of the bicycle ergometer test. The results of a total of 99,068 GS measurements and 3094 CRF measurements are based on a data set at halftime of the NAKO baseline survey (age 20-73 years, 47% men).Males showed higher values of physical fitness compared to women (males: GS = 47.8 kg, VO2max = 36.4 ml·min-1 · kg-1; females: GS = 29.9 kg, VO2max = 32.3 ml · min-1 · kg-1). GS declined from the age of 50 onwards, whereas VO2max levels decreased continuously between the age groups of 20-29 and ≥60 years. GS and VO2max showed a linear positive association after adjustment for body weight (males β = 0.21; females β = 0.35).These results indicate that the physical fitness measured in the NAKO are comparable to other population-based studies. Future analyses in this study will focus on examining the independent relations of GS and CRF with risk of morbidity and mortality.
    • [Physical activity in the German National Cohort (NAKO): use of multiple assessment tools and initial results].

      Leitzmann, Michael; Gastell, Sylvia; Hillreiner, Andrea; Herbolsheimer, Florian; Baumeister, Sebastian E; Bohn, Barbara; Brandes, Mirko; Greiser, Halina; Jaeschke, Lina; Jochem, Carmen; et al. (Springer Open choice, 2020-02-13)
      BACKGROUND: Physical activity is a complex behavior that is difficult to measure validly and reliably in large, population-based studies. Data on physical activity are available for the initial 100,000 participants of the German National Cohort. OBJECTIVES: To describe the baseline physical activity assessment in the cohort and to present initial descriptive results. MATERIAL AND METHODS: Physical activity was assessed using a combination of tools, including two self-administered questionnaires, the Questionnaire on Annual Physical Activity Pattern (QUAP) and the Global Physical Activity Questionnaire (GPAQ); a computer-based 24‑h physical activity recall (cpar24); and 7‑day accelerometry (Actigraph GT3X/+; ActiGraph, Pensacola, FL, USA). RESULTS: The availability of data varied between assessment instruments (QUAP: n = 16,372; GPAQ: n = 90,900; cpar24: n = 23,989; accelerometry: n = 35,218). Analyses across measurement tools showed that on average, women spent 75 to 216 min/d, and men spent 73 to 224 min/d in moderate or higher intensity total physical activity. Persons aged 20-39 years spent 66 to 200 min/d, and persons aged 40-69 years spent 78 to 244 min/d in moderate or higher intensity total physical activity. CONCLUSIONS: Initial baseline analyses of physical activity in this cohort show the value of using a combination of questionnaires, 24‑h recalls, and a movement sensor. The comprehensive data collection represents a valuable resource for future analyses and will improve our understanding of the association between physical activity and disease prevention.
    • [The baseline assessment of the German National Cohort (NAKO Gesundheitsstudie): participation in the examination modules, quality assurance, and the use of secondary data].

      Schipf, Sabine; Schöne, Gina; Schmidt, Börge; Günther, Kathrin; Stübs, Gunthard; Greiser, Karin H; Bamberg, Fabian; Meinke-Franze, Claudia; Becher, Heiko; Berger, Klaus; et al. (Springer, 2020-02-11)
      BACKGROUND: The German National Cohort (NAKO) is an interdisciplinary health study aimed at elucidating causes for common chronic diseases and detecting their preclinical stages. This article provides an overview of design, methods, participation in the examinations, and their quality assurance based on the midterm baseline dataset (MBD) of the recruitment. METHODS: More than 200,000 women and men aged 20-69 years derived from random samples of the German general population were recruited in 18 study centers (2014-2019). The data collection comprised physical examinations, standardized interviews and questionnaires, and the collection of biomedical samples for all participants (level 1). At least 20% of all participants received additional in-depth examinations (level 2), and 30,000 received whole-body magnet resonance imaging (MRI). Additional information will be collected through secondary data sources such as medical registries, health insurances, and pension funds. This overview is based on the MBD, which included 101,839 participants, of whom 11,371 received an MRI. RESULTS: The mean response proportion was 18%. The participation in the examinations was high with most of the modules performed by over 95%. Among MRI participants, 96% completed all 12 MRI sequences. More than 90% of the participants agreed to the use of complementary secondary and registry data. DISCUSSION: Individuals selected for the NAKO were willing to participate in all examinations despite the time-consuming program. The NAKO provides a central resource for population-based epidemiologic research and will contribute to developing innovative strategies for prevention, screening and prediction of chronic diseases.
    • [Nighttime transportation noise annoyance in Germany: personal and regional differences in the German National Cohort Study].

      Wolf, Kathrin; Kraus, Ute; Dzolan, Mihovil; Bolte, Gabriele; Lakes, Tobia; Schikowski, Tamara; Greiser, Karin Halina; Kuß, Oliver; Ahrens, Wolfgang; Bamberg, Fabian; et al. (Springer, 2020-02-11)
      BACKGROUND: Noise annoyance is associated with adverse health-related conditions and reduced wellbeing. Thereby, subjective noise annoyance depends on the objective noise exposure and is modified by personal and regional factors. OBJECTIVE: How many participants of the German National Cohort Study (GNC; NAKO Gesundheitsstudie) were annoyed by transportation noise during nighttime and what factors were associated with noise annoyance? MATERIALS AND METHODS: This cross-sectional analysis included 86,080 participants from 18 study centers, examined from 2014 to 2017. We used multinomial logistic regression to investigate associations of personal and regional factors to noise annoyance (slightly/moderately or strongly/extremely annoyed vs. not annoyed) mutually adjusting for all factors in the model. RESULTS: Two thirds of participants were not annoyed by transportation noise during nighttime and one in ten reported strong/extreme annoyance with highest percentages for the study centers Berlin-Mitte and Leipzig. The strongest associations were seen for factors related to the individual housing situation like the bedroom being positioned towards a major road (OR of being slightly/moderately annoyed: 4.26 [95% CI: 4.01;4.52]; OR of being strongly/extremely annoyed: 13.36 [95% CI: 12.47;14.32]) compared to a garden/inner courtyard. Participants aged 40-60 years and those in low- and medium-income groups reported greater noise annoyance compared to younger or older ones and those in the high-income group. CONCLUSION: In this study from Germany, transportation noise annoyance during nighttime varied by personal and regional factors.
    • [Persons with migration background in the German National Cohort (NAKO)-sociodemographic characteristics and comparisons with the German autochthonous population].

      Wiessner, Christian; Keil, Thomas; Krist, Lilian; Zeeb, Hajo; Dragano, Nico; Schmidt, Börge; Ahrens, Wolfgang; Berger, Klaus; Castell, Stefanie; Fricke, Julia; et al. (Springer, 2020-02-07)
      BACKGROUND: Persons with a migration background (PmM) as a population group usually differ from the autochthonous population in terms of morbidity, mortality, and use of the health care system, but they participate less frequently in health studies. The PmM group is very heterogeneous, which has hardly been taken into account in studies so far. OBJECTIVES: Sociodemographic characteristics of PmM in the NAKO health study (age, sex, time since migration, education) are presented. In addition, it is examined through an example whether migration background is related to the use of cancer screening for colorectal cancer (hemoccult test). METHODS: Data of the first 101,816 persons of the NAKO were analyzed descriptively and cartographically. The migration background was assigned on the basis of the definition of the Federal Statistical Office, based on nationality, country of birth, year of entry, and country of birth of the parents. RESULTS: Overall, the PmM proportion is 16.0%. The distribution across the 18 study centers varies considerably between 6% (Neubrandenburg) and 33% (Düsseldorf). With 153 countries of origin, most countries are represented in the NAKO. All variables show clear differences between the different regions of origin. In the hemoccult test, persons of Turkish origin (OR = 0.67) and resettlers (OR = 0.60) have a lower participation rate. PmM born in Germany do not differ in this respect from the autochthonous population (OR = 0.99). CONCLUSION: PmM in the NAKO are a very heterogeneous group. However, due to the sample size, individual subgroups of migrants can be studied separately with respect to region of origin.
    • Use of Surveillance Outbreak Response Management and Analysis System for Human Monkeypox Outbreak, Nigeria, 2017-2019.

      Silenou, Bernard C; Tom-Aba, Daniel; Adeoye, Olawunmi; Arinze, Chinedu C; Oyiri, Ferdinand; Suleman, Anthony K; Yinka-Ogunleye, Adesola; Dörrbecker, Juliane; Ihekweazu, Chikwe; Krause, Gérard; et al. (Centers for Disease Control and Prevention (CDC), 2020-02-01)
      In November 2017, the mobile digital Surveillance Outbreak Response Management and Analysis System was deployed in 30 districts in Nigeria in response to an outbreak of monkeypox. Adaptation and activation of the system took 14 days, and its use improved timeliness, completeness, and overall capacity of the response.
    • Factors associated with habitual time spent in different physical activity intensities using multiday accelerometry.

      Jaeschke, Lina; Steinbrecher, Astrid; Boeing, Heiner; Gastell, Sylvia; Ahrens, Wolfgang; Berger, Klaus; Brenner, Hermann; Ebert, Nina; Fischer, Beate; Greiser, Karin Halina; et al. (NPG, 2020-01-21)
      To investigate factors associated with time in physical activity intensities, we assessed physical activity of 249 men and women (mean age 51.3 years) by 7-day 24h-accelerometry (ActiGraph GT3X+). Triaxial vector magnitude counts/minute were extracted to determine time in inactivity, in low-intensity, moderate, and vigorous-to-very-vigorous activity. Cross-sectional associations with sex, age, body mass index, waist circumference, smoking, alcohol consumption, education, employment, income, marital status, diabetes, and dyslipidaemia were investigated in multivariable regression analyses. Higher age was associated with more time in low-intensity (mean difference, 7.3 min/d per 5 years; 95% confidence interval 2.0,12.7) and less time in vigorous-to-very-vigorous activity (-0.8 min/d; -1.4, -0.2), while higher BMI was related to less time in low-intensity activity (-3.7 min/d; -6.3, -1.2). Current versus never smoking was associated with more time in low-intensity (29.2 min/d; 7.5, 50.9) and less time in vigorous-to-very-vigorous activity (-3.9 min/d; -6.3, -1.5). Finally, having versus not having a university entrance qualification and being not versus full time employed were associated with more inactivity time (35.9 min/d; 13.0, 58.8, and 66.2 min/d; 34.7, 97.7, respectively) and less time in low-intensity activity (-31.7 min/d; -49.9, -13.4, and -50.7; -76.6, -24.8, respectively). The assessed factors show distinct associations with activity intensities, providing targets for public health measures aiming to increase activity.
    • Socio-demographic and employment-related factors in the German National Cohort (GNC; NAKO Gesundheitsstudie)

      Dragano, Nico; Reuter, Marvin; Greiser, Karin Halina; Becher, Heiko; Zeeb, Hajo; Mikolajczyk, Rafael; Kluttig, Alexander; Leitzmann, Michael; Fischer, Beate; Jöckel, Karl Heinz; et al. (Springer, 2020-01-01)
      igh levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research. The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging. BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes. The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases.
    • Anthropometric measures in the German National Cohort—more than weight and height

      Fischer, Beate; Sedlmeier, Anja M.; Hartwig, Saskia; Schlett, Christopher L.; Ahrens, Wolfgang; Bamberg, Fabian; Baurecht, Hansjörg; Becher, Heiko; Berger, Klaus; Binder, Hans; et al. (Springer, 2020-01-01)
      High levels of adiposity in the population have a major impact on various diseases, but previous epidemiologic studies have largely been restricted to simple anthropometric measures such as the body mass index (BMI), an imperfect predictor of disease risk. There is a critical need for the use of improved measures of relative weight and body composition in large-scale, population-based research. The current article presents initial descriptive results of body composition and fat distribution based on the midterm baseline dataset of the German National Cohort, which included 101,817 participants who were examined in 18 study centers in Germany between March 2014 and March 2017. The anthropometric measures encompassed body weight, height, waist and hip circumference, bioelectrical impedance analysis (BIA), sonography of abdominal adipose tissue, 3D-body scanning, and magnetic resonance imaging. BMI analyses showed that 46.2% of men and 29.7% of women were overweight and 23.5% of men and 21.2% of women were obese. On average, women in almost all age groups demonstrated more subcutaneous adipose tissue layer thickness than men. The mean values of visceral adipose tissue layer thickness, on the other hand, were higher among men than among women in all age groups and increased continuously across age groups in both sexes. The comprehensive assessment of body composition and fat distribution provides novel future opportunities for detailed epidemiologic analyses of overweight and adiposity in relation to the development of chronic diseases. © 2020, The Author(s).
    • A probabilistic projection of beneficiaries of long-term care insurance in Germany by severity of disability

      Vanella, Patrizio; Heß, Moritz; Wilke, Christina B.; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Springer, 2020-01-01)
      Demographic aging puts social insurance systems under immense pressure as frailty risks increase with age. The statutory long-term care insurance in Germany (GPV), whose society has been aging for decades due to low fertility and decreasing mortality, faces massive future pressure. The present study presents a stochastic outlook on long-term care insurance in Germany until 2045 by forecasting the future number of frail persons who could claim insurance services by severity level with theory-based Monte Carlo simulations. The simulations result in credible intervals for age-, sex- and severity-specific care rates as well as the numbers of persons for all combinations of age, sex and severity by definition of the GPV on an annual basis. The model accounts for demographic trends through time series analysis and considers all realistic epidemiological developments by simulation. The study shows that increases in the general prevalence of disabilities, especially for severe disabilities, caused by the demographic development in Germany are unavoidable, whereas the influence of changes in agespecific care risks does not affect the outcome significantly. The results may serve as a basis for estimating the future demand for care nurses and the financial expenses of the GPV.
    • Safety profile of rubella vaccine administered to pregnant women: A systematic review of pregnancy related adverse events following immunisation, including congenital rubella syndrome and congenital rubella infection in the foetus or infant.

      Mangtani, Punam; Evans, Stephen J W; Lange, Berit; Oberle, Doris; Smith, Julianna; Drechsel-Baeuerle, Ursula; Keller-Stanislawski, Brigitte; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (Elsevier, 2019-12-12)
      Background: Data on the safety of inadvertent rubella vaccination in pregnancy is important for rubella vaccination programs aimed at preventing congenital rubella syndrome. Methods: The association between monovalent rubella or combination vaccinations in or shortly before pregnancy and potential harm to the foetus was examined by conducting a systematic review and meta-analysis using fixed effect methods and simulation. Results: Four cohort studies of inadvertently vaccinated and unvaccinated women were found, 15 cohorts of pregnant women who were rubella susceptible at time of inadvertent vaccination and 9 cohort studies with no information on susceptibility and case series. No case of vaccine associated congenital rubella syndrome (CRS) was identified. Cohort studies with an unvaccinated comparison group were limited in number and size, and based on these only a theoretical additional risk of 6 or more cases of CRS per 1000 vaccinated women (0% observed, upper 95% CI 0.6%) could be excluded. Based on cohorts of vaccinated rubella susceptible pregnant women a maximum theoretical risk of 1 CRS case in 1008 vaccinated women (0% observed, upper 95% CI 0.099%) was estimated. Asymptomatic rubella vaccine virus infection of the neonate was also noted (fixed effects estimate of risk overall 1.74%, 95% CI 1.21, 2.28). Conclusion: There is no evidence that CRS is caused by rubella-containing vaccines but transplacental vaccine virus infection can occur. CRS is effectively prevented by vaccination, thus the risk/benefit balance is unequivocally in favour of vaccination. The data confirm previous recommendations that inadvertent vaccination during pregnancy is not an indication for termination of pregnancy.
    • Staphylococcus aureus Exploits the Host Apoptotic Pathway To Persist during Infection.

      Winstel, Volker; Schneewind, Olaf; Missiakas, Dominique; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (American Society of Microbiology, 2019-11-12)
      Staphylococcus aureus is a deadly pathogen that causes fatal diseases in humans. During infection, S. aureus secretes nuclease (Nuc) and adenosine synthase A (AdsA) to generate cytotoxic deoxyadenosine (dAdo) from neutrophil extracellular traps which triggers noninflammatory apoptosis in macrophages. In this manner, replicating staphylococci escape phagocytic killing without alerting the immune system. Here, we show that mice lacking caspase-3 in immune cells exhibit increased resistance toward S. aureus Caspase-3-deficient macrophages are resistant to staphylococcal dAdo and gain access to abscess lesions to promote bacterial clearance in infected animals. We identify specific single nucleotide polymorphisms in CASP3 as candidate human resistance alleles that protect macrophages from S. aureus-derived dAdo, raising the possibility that the allelic repertoire of caspase-3 may contribute to the outcome of S. aureus infections in humans.IMPORTANCE Caspase-3 controls the apoptotic pathway, a form of programmed cell death designed to be immunologically silent. Polymorphisms leading to reduced caspase-3 activity are associated with variable effects on tumorigenesis and yet arise frequently. Staphylococcus aureus is a human commensal and a frequent cause of soft tissue and bloodstream infections. Successful commensalism and virulence can be explained by the secretion of a plethora of immune evasion factors. One such factor, AdsA, destroys phagocytic cells by exploiting the apoptotic pathway. However, human CASP3 variants with loss-of-function alleles shield phagocytes from AdsA-mediated killing. This finding raises the possibility that some caspase-3 alleles may arise from exposure to S. aureus and other human pathogens that exploit the apoptotic pathway for infection.
    • Establishment of a highly sensitive assay for detection of Hepatitis E virus-specific immunoglobulins.

      Bohm, Katrin; Strömpl, Julia; Krumbholz, Andi; Zell, Roland; Krause, Gérard; Sievers, Claudia; HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. (ASM, 2019-11-06)
      Hepatitis E, a liver disease caused by infection with the hepatitis E virus (HEV) is a worldwide emerging disease. The diagnosis is based on the detection of viral RNA and of HEV-specific immunoglobulins (Ig). For the latter, various assays are commercially available but still lack harmonization.In this study, a Luminex®-based multiplex serological assay was established, that measures the presence of total IgG, IgA and IgM antibodies, targeting a short peptide derived from the viral E2 protein. For the validation, 160 serum samples with a known HEV serostatus were used to determine the assay cut-off and accuracy. Thereby, HEV-IgG and -RNA positive sera were identified with a sensitivity of 100% and a specificity of 98% [CI95% 94-100%].Application of the assay by re-testing 514 sera previously characterised with different HEV-IgG or total antibody tests, revealed a high level of agreement between the assays (Cohens Kappa 0.58-0.99).The established method is highly sensitive, specific and can be easily implemented in a multiplex format to facilitate rapid differential diagnostics with a few microliters of sample input.
    • Labour characteristics of women achieving successful vaginal birth after caesarean section in three European countries.

      Gross, Mechthild M; Clarke, Mike; Begley, Cecily; Daly, Deirdre; Healy, Patricia; Nicoletti, Jane; Devane, Declan; Morano, Sandra; Krause, Gérard; Karch, André; et al. (Elsevier, 2019-07-01)
      Objective: Knowledge about labour characteristics of women achieving successful vaginal birth after caesarean section (VBAC) might be used to improve labour and birth management. This study examined sociodemographic and labour process-related factors regarding a) differences between countries, b) the comparison of successful VBAC with unplanned caesarean section, and c) predictors for the success of planned VBAC in three European countries. Design: We analysed observational data collected within the OptiBIRTH trial, a clusterrandomised controlled trial. Setting: Fifteen study sites in Ireland, Italy and Germany, five in each country. Participants: 790 participants going into labour for planned VBAC. Measurements: Descriptive statistics and random-effects logistic regression models were applied. Findings: The pooled successful VBAC-rate was 74.6%. Italy had the highest proportion of women receiving none of the four intrapartum interventions amniotomy (ARM), oxytocin, epidural or opioids (42.5% vs Ireland: 26.8% and Germany: 25.3%, p<0.001). Earlier performance of ARM was associated with successful VBAC (3.50 hrs vs 6.08 hrs, p=0.004). A positive predictor for successful vaginal birth was a previous vaginal birth (OR=3.73, 95% CI [2.17, 6.44], p<0.001). The effect of ARM increased with longer labour duration (OR for interaction term=1.06, 95% CI [1.004, 1.12], p=0.035). Higher infant birthweight (OR per kg=0.34, 95% CI [0.23, 0.50], p<0.001), ARM (reference spontaneous rupture of membranes (SROM), OR=0.20, 95% CI [0.11, 0.37], p<0.001) and a longer labour duration (OR per hour=0.93, 95% CI [0.90, 0.97], p<0.001) decreased the odds of a vaginal birth. Key conclusion: Women with a previous vaginal birth, an infant with a lower birth weight, SROM and a shorter labour duration were most likely to have a successful vaginal birth. If SROM did not occur, an earlier ARM increased the odds of a vaginal birth. Implication for practice: Labour progress should be accelerated by fostering endogenous uterine contractions. With slow labour progress and intact membranes, ARM might increase the chance of a vaginal birth
    • Guidelines and recommendations for ensuring Good Epidemiological Practice (GEP): a guideline developed by the German Society for Epidemiology.

      Hoffmann, Wolfgang; Latza, Ute; Baumeister, Sebastian E; Brünger, Martin; Buttmann-Schweiger, Nina; Hardt, Juliane; Hoffmann, Verena; Karch, André; Richter, Adrian; Schmidt, Carsten Oliver; et al. (Springer, 2019-03-01)
      Objective To revise the German guidelines and recommendations for ensuring Good Epidemiological Practice (GEP) that were developed in 1999 by the German Society for Epidemiology (DGEpi), evaluated and revised in 2004, supplemented in 2008, and updated in 2014. Methods The executive board of the DGEpi tasked the third revision of the GEP. The revision was arrived as a result of a consensus-building process by a working group of the DGEpi in collaboration with other working groups of the DGEpi and with the German Association for Medical Informatics, Biometry and Epidemiology, the German Society of Social Medicine and Prevention (DGSMP), the German Region of the International Biometric Society (IBS-DR), the German Technology, Methods and Infrastructure for Networked Medical Research (TMF), and the German Network for Health Services Research (DNVF). The GEP also refers to related German Good Practice documents (e.g. Health Reporting, Cartographical Practice in the Healthcare System, Secondary Data Analysis). Results The working group modified the 11 guidelines (after revision: 1 ethics, 2 research question, 3 study protocol and manual of operations, 4 data protection, 5 sample banks, 6 quality assurance, 7 data storage and documentation, 8 analysis of epidemiological data, 9 contractual framework, 10 interpretation and scientific publication, 11 communication and public health) and modified and supplemented the related recommendations. All participating scientific professional associations adopted the revised GEP. Conclusions The revised GEP are addressed to everyone involved in the planning, preparation, execution, analysis, and evaluation of epidemiological research, as well as research institutes and funding bodies.
    • Herpes zoster incidence in Germany - an indirect validation study for self-reported disease data from pretest studies of the population-based German National Cohort.

      Caputo, Mahrrouz; Horn, Johannes; Karch, André; Akmatov, Manas K; Becher, Heiko; Braun, Bettina; Brenner, Hermann; Castell, Stefanie; Fischer, Beate; Giani, Guido; et al. (2019-01-30)
      Until now, herpes zoster (HZ)-related disease burden in Germany has been estimated based on health insurance data and clinical findings. However, the validity of self-reported HZ is unclear. This study investigated the validity of self-reported herpes zoster (HZ) and its complication postherpetic neuralgia (PHN) using data from the pretest studies of the German National Cohort (GNC) in comparison with estimates based on health insurance data. Data of 4751 participants aged between 20 and 69 years from two pretest studies of the GNC carried out in 2011 and 2012 were used. Based on self-reports of physician-diagnosed HZ and PHN, age- and sex-specific HZ incidence rates and PHN proportions were estimated. For comparison, estimates based on statutory health insurance data from the German population were considered. Eleven percent (95%-CI, 10.4 to 12.3, n = 539) of the participants reported at least one HZ episode in their lifetime. Our estimated age-specific HZ incidence rates were lower than previous estimates based on statutory health insurance data. The PHN proportion in participants older than 50 years was 5.9% (1.9 to 13.9%), which was in line with estimates based on health insurance data. As age- and sex-specific patterns were comparable with that in health insurance data, self-reported diagnosis of HZ seems to be a valid instrument for overall disease trends. Possible reasons for observed differences in incidence rates are recall bias in self-reported data or overestimation in health insurance data.
    • Design and characterization of dietary assessment in the German National Cohort.

      Knüppel, Sven; Clemens, Matthias; Conrad, Johanna; Gastell, Sylvia; Michels, Karin B; Leitzmann, Michael; Krist, Lilian; Pischon, Tobias; Krause, Gerard; Ahrens, Wolfgang; et al. (Springer Nature, 2019-01-15)
      BACKGROUND/OBJECTIVES: The aim of the study was to describe a novel dietary assessment strategy based on two instruments complemented by information from an external population applied to estimate usual food intake in the large-scale multicenter German National Cohort (GNC). As proof of concept, we applied the assessment strategy to data from a pretest study (2012-2013) to assess the feasibility of the novel assessment strategy. SUBJECTS/METHODS: First, the consumption probability for each individual was modeled using three 24 h food lists (24h-FLs) and frequencies from one food frequency questionnaire (FFQ). Second, daily consumed food amounts were estimated from the representative German National Nutrition Survey II (NVS II) taking the characteristics of the participants into account. Usual food intake was estimated using the product of consumption probability and amounts. RESULTS: We estimated usual intake of 41 food groups in 318 men and 377 women. The participation proportion was 100, 84.4, and 68.5% for the first, second, and third 24h-FL, respectively. We observed no associations between the probability of participating and lifestyle factors. The estimated distributions of usual food intakes were plausible and total energy was estimated to be 2707 kcal/day for men and 2103 kcal/day for women. The estimated consumption frequencies did not differ substantially between men and women with only few exceptions. The differences in energy intake between men and women were mostly due to differences in estimated daily amounts. CONCLUSIONS: The combination of repeated 24h-FLs, a FFQ, and consumption-day amounts from a reference population represents a user-friendly dietary assessment approach having generated plausible, but not yet validated, food intake values in the pretest study