[BeoNet-Halle-development of a multifunctional database for the automated extraction of healthcare data from general practitioner and specialist practices]. / BeoNet-Halle ­ Aufbau einer multifunktionalen Datenbank zur automatisierten Extraktion von Versorgungsdaten aus Haus- und Facharztpraxen.

The Beobachtungspraxennetzwerk Halle (BeoNet-Halle) is an innovative database of outpatient care that has been collecting patient data from participating primary care and specialty practices throughout Germany since 2020 and making it available for research and care. The database is set up and maintained by the Institute of Medical Epidemiology, Biometrics and Informatics and the Institute of General Practice and Family Medicine of the Martin Luther University Halle-Wittenberg. Furthermore, the Data Integration Center of the University Medical Center Halle is involved in the project. In principle, anonymized and pseudonymized patient data from all commercially available practice management systems should flow into the databases.In this article, we describe the structure and methods of the multi-purpose database BeoNet and quantify the current data stock. The workflow of collection, transfer, and storage of broad consents is described and advantages and limitations of the database are discussed.BeoNet-Halle currently contains anonymized data of approximately 73,043 patients from five physician practices. Furthermore, it includes data from more than 2,653,437 ICD-10 diagnoses, 1,403,726 prescriptions, and 1,894,074 laboratory results. Pseudonymized data were successfully exported from 481 patients.BeoNet-Halle enables an almost seamless representation of the care provided in the participating practices. In the future, the database will map patient treatment pathways across practices and provide high-quality care data to contribute to health policy decision-making and optimization of care processes.

Cardiovascular risk factors, living and ageing in Halle: the CARLA study.

The CARLA study (Cardiovascular Disease, Living and Ageing in Halle) is a longitudinal population-based cohort study of the general population of the city of Halle (Saale), Germany. The primary aim of the cohort was to investigate risk factors for cardiovascular diseases based on comprehensive cardiological phenotyping of study participants and was extended to study factors associated with healthy ageing. In total, 1779 probands (812 women and 967 men, aged 45-83 years) were examined at baseline (2002-2005), with a first and second follow-up performed 4 and 8 years later. The response proportion at baseline was 64.1% and the reparticipation proportion for the first and second follow-up was 86% and 77% respectively. Sixty-four percent of the study participants were in retirement while 25% were full- or partially-employed and 11% were unemployed at the time of the baseline examination. The currently running third follow-up focuses on the assessment of physical and mental health, with an intensive 4 h examination program, including measurement of cardiovascular, neurocognitive, balance and gait parameters. The data collected in the CARLA Study resulted in answering various research questions in over 80 publications, of which two thirds were pooled analyses with other similar population-based studies. Due to the extensiveness of information on risk factors, subclinical conditions and evident diseases, the biobanking concept for the biosamples, the cohort representativeness of an elderly population, and the high level of quality assurance, the CARLA cohort offers a unique platform for further research on important indicators for healthy ageing.

Outpatient health care utilization and health expenditures of asylum seekers in Halle (Saale), Germany - an analysis of claims data.

BACKGROUND: Asylum seekers are a vulnerable group with special needs in health care due to their migration history and pre-, peri- and postmigratory social determinants of health. However, in Germany access to health care is restricted for asylum seekers by law and administrative regulations. METHODS: Using claims data generated in the billing process of health care services provided to asylum seekers, we explore their utilization of health care services in the outpatient sector. We describe the utilization of outpatient specialties, prevalences of diagnoses, prescribed drugs and other health care services, as well as total costs of health care provision. RESULTS: The estimated prevalence for visiting an ambulatory physician at least once per year was 67.5% [95%-Confidence-Interval (CI): 65.1-69.9%], with a notably higher prevalence for women than men. The diagnoses with the highest one-year prevalence were "Acute upper respiratory infections" (16.1% [14.5-18.0%]), "Abdominal and pelvic pain" (15.6% [13.9-17.4%]) and "Dorsalgia" (13.8% [12.2-15.5%]). A total of 21% of all prescriptions were for common pain killers. Women received more diagnoses across most diagnosis groups and prescribed drugs from all types than men. Less than half (45.3%) of all health care costs were generated in the outpatient sector. CONCLUSION: The analysis of claims data held in a municipal social services office is a novel approach to gain better insight into asylum seekers' utilization of health services on an individual level. Compared to regularly insured patients, four characteristics in health care utilization by asylum seekers were identified: low utilization of ambulatory physicians; a gender gap in almost all services, with higher utilization by women; frequent prescription of pain killers; and a low proportion of overall health care costs generated in the outpatient sector. Further research is needed to describe structural and individual factors producing these anomalies.

[Psychoeducation in knee arthroplasty patients : Additional pain management]. / Psychoedukation bei Patienten mit Knieendoprothese : Erweitertes Schmerzmanagement.

Approximately 20-30% of patients remain dissatisfied with their treatment outcome after primary knee arthroplasty. Particularly frequent pain with limited flexibility contrives to reduce the quality of life of affected patients. Psychotherapeutic methods for pain processing after knee arthroplasty have hardly been investigated to date. The current study is dedicated to researching the effect of pain psychoeducation on treatment outcome after primary knee arthroplasty in the sense of additional pain management.

[Anthropometric measures in the German National Cohort-more than weight and height]. / Anthropometrische Messungen in der NAKO Gesundheitsstudie ­ mehr als nur Größe und Gewicht.

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.

Advanced glycation end products and their ratio to soluble receptor are associated with limitations in physical functioning only in women: results from the CARLA cohort.

BACKGROUND: Advanced glycation end products (AGEs), modifications of proteins or amino acids, are increasingly produced and accumulated with age-related diseases. Recent studies suggested that the ratio of AGEs and their soluble receptor (sRAGE) is a more accurate biomarker for age-related diseases than each separately. We aim to investigate whether this also applies for physical functioning in a broad age-spectrum. METHODS: AGE and sRAGE levels, and physical functioning (SF-12 questionnaire) of 967 men and 812 women (45-83 years) were measured in the CARLA study. We used ordinal logistic regression to examine associations between AGEs, sRAGE, and AGE/sRAGE ratio with physical functioning in sex- and age-stratified models. RESULTS: Higher levels of AGEs and AGE/sRAGE ratio were associated with lower physical functioning only in women, even after consideration of classical lifestyle and age-related factors (education, BMI, smoking, alcohol consumption, diet, creatinine clearance, diabetes mellitus, lipid lowering and antihypertensive drugs) (odds ratio (OR) =0.86, 95%confidence interval = 0.74-0.98 and OR = 0.86, 95%CI = 0.75-0.98 for AGEs and AGE/sRAGE ratio respectively). We could not demonstrate a significant difference across age. CONCLUSIONS: We showed a sex-specific association between physical functioning and AGEs and AGE/sRAGE, but no stronger associations of the latter with physical functioning. Further investigation is needed in the pathophysiology of this association.

Risk-based approach to school entry examinations in Germany - a validation study.

BACKGROUND: In Germany, all preschoolers undergo a school entry examination (SEE). While most children are sufficiently served with standardized developmental tests only, for a small group of otherwise underserved children, the SEE should also include a subsidiary health checkup. The aim of the study was to validate selection criteria to differentiate these two groups of children. METHODS: Secondary data from the SEEs of 2016 and 2017 that contained information on 3513 children were analyzed. Of these children, a subset was selected in which no severe developmental disorders were diagnosed prior to the SEE (n = 2744). The selection criteria identified in an earlier study (low or medium social status, missed the last pediatric routine check-up, migration background, three or more siblings, and raised by a single mother) were then applied to this subset to estimate their effectiveness in finding children at risk for a newly diagnosed severe developmental disorder. The sensitivity, specificity and positive and negative predictive values of the selection criteria were calculated. RESULTS: The tested selection criteria identified children who would likely benefit from a subsidiary checkup in the context of SEEs with a sensitivity of 96% (95% CI: 94.5-98.9%). The negative predictive value and specificity of the criteria were 99% (98.6-99.7%) and 34% (32.1-35.8%), respectively. By using this approach, the number of children seen by a physician could be reduced to 53% of the age cohorts. CONCLUSION: The tested selection criteria are a viable way to differentiate children for whom SEEs should include a subsidiary health checkup from those who do not need it. Therefore, the time that physicians spend with SEEs could be reduced. Using the selection criteria to establish a stepped procedure in SEEs therefore offers a valid way to focus physicians' resources on the children who need them most.

[Assessing incident cardiovascular and metabolic diseases in epidemiological cohort studies in Germany]. / Erfassung inzidenter kardiovaskulärer und metabolischer Erkrankungen in epidemiologischen Kohortenstudien in Deutschland.

BACKGROUND: Cardiovascular and metabolic diseases are a major cause of mortality and loss of quality of life in Germany. Research into risk factors of these diseases requires large population-based cohort studies. Complete and accurate assessment of the incidence of cardiovascular and metabolic diseases is a key element for valid interpretation of the results from such studies. OBJECTIVE: Our aim was to identify population-based cohort studies with incidence of cardiovascular and metabolic diseases in Germany and to summarize their methods for assessment and classification of disease endpoints, including myocardial infarction, type 2 diabetes, stroke, heart failure, and arterial hypertension. METHODS: Within the framework of a workshop, representatives of the ascertained population-based cohort studies in Germany with incidence of cardiovascular or metabolic diseases were invited to present and to systematically provide information on their methods of endpoint identification. RESULTS: We identified eight studies from different regions in Germany with a total of 100,571 participants, aged 18-83 years at baseline. Self-reporting by study participants is the major source for further inquiries to assess disease endpoints in these studies. Most studies use additional data sources to verify the incidence of diseases, such as documents provided by the treating physician or hospital. CONCLUSIONS: Our results highlight the central role of self-reporting and the efforts associated with identification and verification of disease endpoints in cohort studies. They also provide a basis for future population-based studies that aim for standardized assessment of the incidence of cardiovascular and metabolic diseases.

Prognostic relevance of the interaction between short-term, metronome-paced heart rate variability, and inflammation: results from the population-based CARLA cohort study.

AIMS: To determine the interaction between HRV and inflammation and their association with cardiovascular/all-cause mortality in the general population. METHODS AND RESULTS: Subjects of the CARLA study (n = 1671; 778 women, 893 men, 45-83 years of age) were observed for an average follow-up period of 8.8 years (226 deaths, 70 cardiovascular deaths). Heart rate variability parameters were calculated from 5-min segments of 20-min resting electrocardiograms. High-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and soluble tumour necrosis factor-alpha receptor type 1 (sTNF-R1) were measured as inflammation parameters. The HRV parameters determined included the standard deviation of normal-to-normal intervals (SDNN), the root-mean-square of successive normal-interval differences (RMSSD), the low- and high-frequency (HF) power, the ratio of both, and non-linear parameters [Poincaré plot (SD1, SD2, SD1/SD2), short-term detrended fluctuation analysis]. We estimated hazard ratios by using covariate-adjusted Cox regression for cardiovascular and all-cause mortality incorporating an interaction term of HRV/inflammation parameters. Relative excess risk due to interactions (RERIs) were computed. We found an interaction effect of sTNF-R1 with SDNN (RERI: 0.5; 99% confidence interval (CI): 0.1-1.0), and a weaker effect with RMSSD (RERI: 0.4; 99% CI: 0.0-0.9) and HF (RERI: 0.4; 99% CI: 0.0-0.9) with respect to cardiovascular mortality on an additive scale after covariate adjustment. Neither IL-6 nor hsCRP showed a significant interaction with the HRV parameters. CONCLUSION: A change in TNF-α levels or the autonomic nervous system influences the mortality risk through both entities simultaneously. Thus, TNF-α and HRV need to be considered when predicating mortality.

Longitudinal association of short-term, metronome-paced heart rate variability and echocardiographically assessed cardiac structure at a 4-year follow-up: results from the prospective, population-based CARLA cohort.

AIMS: To assess the value of cardiac structure/function in predicting heart rate variability (HRV) and the possibly predictive value of HRV on cardiac parameters. METHODS AND RESULTS: Baseline and 4-year follow-up data from the population-based CARLA cohort were used (790 men, 646 women, aged 45-83 years at baseline and 50-87 years at follow-up). Echocardiographic and HRV recordings were performed at baseline and at follow-up. Linear regression models with a quadratic term were used. Crude and covariate adjusted estimates were calculated. Missing values were imputed by means of multiple imputation. Heart rate variability measures taken into account consisted of linear time and frequency domain [standard deviation of normal-to-normal intervals (SDNN), high-frequency power (HF), low-frequency power (LF), LF/HF ratio] and non-linear measures [detrended fluctuation analysis (DFA1), SD1, SD2, SD1/SD2 ratio]. Echocardiographic parameters considered were ventricular mass index, diastolic interventricular septum thickness, left ventricular diastolic dimension, left atrial dimension systolic (LADS), and ejection fraction (Teichholz). A negative quadratic relation between baseline LADS and change in SDNN and HF was observed. The maximum HF and SDNN change (an increase of roughly 0.02%) was predicted at LADS of 3.72 and 3.57 cm, respectively, while the majority of subjects experienced a decrease in HRV. There was no association between further echocardiographic parameters and change in HRV, and there was no evidence of a predictive value of HRV in the prediction of changes in cardiac structure. CONCLUSION: In the general population, LADS predicts 4-year alteration in SDNN and HF non-linearly. Because of the novelty of the result, analyses should be replicated in other populations.

Short-term blood pressure variability - variation between arm side, body position and successive measurements: a population-based cohort study.

BACKGROUND: Precise blood pressure (BP) measurements are central for the diagnosis of hypertension in clinical and epidemiological studies. The purpose of this study was to quantify the variability in BP associated with arm side, body position, and successive measurements in the setting of a population-based observational study. Additionally, we aimed to evaluate the influence of different measurement conditions on prevalence of hypertension. METHODS: The sample included 967 men and 812 women aged 45 to 83 years at baseline. BP was measured according to a standardized protocol with oscillometric devices including three sitting measurements at left arm, one simultaneous supine measurement at both arms, and four supine measurements at the arm with the higher BP. Hypertension was defined as systolic BP (SBP) ≥140 mmHg and/or diastolic BP (DBP) ≥90 mmHg. Variability in SBP and DBP were analysed with sex-stratified linear covariance pattern models. RESULTS: We found that overall, no mean BP differences were measured according to arm-side, but substantial higher DBP and for men also higher SBP was observed in sitting than in supine position and there was a clear BP decline by consecutive measurement. Accordingly, the prevalence of hypertension depends strongly on the number and scheme of BP measurements taken to calculate the index values. CONCLUSIONS: Thus, BP measurements should only be compared between studies applying equal measurement conditions and index calculation. Moreover, the first BP measurement should not be used to define hypertension since it overestimates BP. The mean of second and third measurement offers the advantage of better reproducibility over single measurements.

Health literacy in an urban elderly East-German population - results from the population-based CARLA study.

BACKGROUND: Health literacy (HL) has gained increasing attention in public health research. However, until now research was mainly focused on clinical settings rather than on the general population. Due its relation to social determinants and health outcomes, HL is of special interest in epidemiological studies. The aim of the present study was therefore to describe HL among an elderly general high-risk population, to analyze the potential contributing factors of HL, and to analyze the impact of HL on health-related outcomes. METHODS: We used data from the CARLA Study, which is a prospective population-based cohort study of the elderly general population of the city of Halle (Saale) in Eastern Germany. The short version of the HLS-EU Questionnaire (HLS-EU-Q16) was administered with 1,107 subjects aged between 55 and 91 year old. A HL score ranging from 0 to 50 points was computed and classified according to the recommendation of the HLS-EU project. Socio-economic as well as health-related variables were determined during the standardized interview and clinical examination. We calculated linear as well as logistic regression models in order to analyze the association between HL and health-related outcomes as well as potential influencing factors of HL. RESULTS: Overall, the HL score was 36.9 (SD 6.9). Among all subjects, 4 % showed inadequate HL, 23 % problematic HL, 50 % sufficient HL, and 23 % excellent HL. HL was positively associated with educational level, net household income, and self-perceived social position. Further, we found an increase of HL with age (ß = 0.10; 95 % CL 0.05; 0.15) and a lower HL score among women compared with men (Diff = -1.4; 95 % CL -2.2; -0.6). An inverse association was observed between HL and diabetes among both sexes (OR 0.93; 95 % CL 0.93; 0.98), between HL and myocardial infarction among women, and between HL and stroke among men. CONCLUSIONS: In this elderly general Eastern German population, we found higher HL score values compared with previous studies using the same questionnaire. HL was associated with socio-economic status. Furthermore, this cross-sectional study could show associations between HL and different health-related outcomes even after adjustment for educational level. However, further research is needed in order to evaluate the impact of HL on health-related outcomes using longitudinal data derived from the general population.

Meta-analysis of two genome-wide association studies identifies four genetic loci associated with thyroid function.

Thyroid hormones play key roles in cellular growth, development and metabolism. Although there is a strong genetic influence on thyroid hormone levels, the genes involved are widely unknown. The levels of circulating thyroid hormones are tightly regulated by thyrotropin (TSH), which also represents the most important diagnostic marker for thyroid function. Therefore, in order to identify genetic loci associated with TSH levels, we performed a discovery meta-analysis of two genome-wide association studies including two cohorts from Germany, KORA (n = 1287) and SHIP (n = 2449), resulting in a total sample size of 3736. Four genetic loci at 5q13.3, 1p36, 16q23 and 4q31 were associated with serum TSH levels. The lead single-nucleotide polymorphisms of these four loci were located within PDE8B encoding phosphodiesterase 8B, upstream of CAPZB that encodes the ß-subunit of the barbed-end F-actin-binding protein, in a former 'gene desert' that was recently demonstrated to encode a functional gene (LOC440389) associated with thyroid volume, and upstream of NR3C2 encoding the mineralocorticoid receptor. The latter association for the first time suggests the modulation of thyroid function by mineral corticoids. All four loci were replicated in three additional cohorts: the HUNT study from Norway (n = 1487) and the two German studies CARLA (CARLA, n = 1357) and SHIP-TREND (n = 883). Together, these four quantitative trait loci accounted for ∼3.3% of the variance in TSH serum levels. These results contribute to our understanding of genetic factors and physiological mechanisms mediating thyroid function.

Association of childhood and adult socioeconomic indicators with cardiovascular risk factors and its modification by age: the CARLA Study 2002-2006.

BACKGROUND: The influence of socioeconomic status (SES) on cardiovascular diseases and risk factors is widely known, although the role of different SES indicators is not fully understood. The aim of this study was to investigate the role of different SES indicators for cardiovascular disease risk factors in a middle and old aged East German population. METHODS: Cross-sectional data of an East German population-based cohort study (1779 men and women aged 45 to 83) were used to assess the association of childhood and adulthood SES indicators (childhood SES, education, occupational position, income) with cardiovascular risk factors. Adjusted means and odds ratios of risk factors by SES indicators with 95% confidence intervals (CI) were calculated by linear and logistic regression models, stratified by sex. The interaction effect of education and age on cardiovascular risk factors was tested by including an interaction term. RESULTS: In age-adjusted models, education, occupational position, and income were statistically significantly associated with abdominal obesity in men, and with smoking in both sexes. Men with low education had a more than threefold risk of being a smoker (OR 3.44, CI 1.58-7.51). Low childhood SES was associated with higher systolic blood pressure and abdominal obesity in women (OR 2.27, CI 1.18-4.38 for obesity); a non-significant but (in terms of effect size) relevant association of childhood SES with smoking was observed in men. In women, age was an effect modifier for education in the risk of obesity and smoking. CONCLUSIONS: We found considerable differences in cardiovascular risk factors by education, occupational position, income, and partly by childhood social status, differing by sex. Some social inequalities levelled off in higher age. Longitudinal studies are needed to differentiate between age and birth cohort effects.

Algorithmic surveillance of ICU patients with acute respiratory distress syndrome (ASIC): protocol for a multicentre stepped-wedge cluster randomised quality improvement strategy.

INTRODUCTION: The acute respiratory distress syndrome (ARDS) is a highly relevant entity in critical care with mortality rates of 40%. Despite extensive scientific efforts, outcome-relevant therapeutic measures are still insufficiently practised at the bedside. Thus, there is a clear need to adhere to early diagnosis and sufficient therapy in ARDS, assuring lower mortality and multiple organ failure. METHODS AND ANALYSIS: In this quality improvement strategy (QIS), a decision support system as a mobile application (ASIC app), which uses available clinical real-time data, is implemented to support physicians in timely diagnosis and improvement of adherence to established guidelines in the treatment of ARDS. ASIC is conducted on 31 intensive care units (ICUs) at 8 German university hospitals. It is designed as a multicentre stepped-wedge cluster randomised QIS. ICUs are combined into 12 clusters which are randomised in 12 steps. After preparation (18 months) and a control phase of 8 months for all clusters, the first cluster enters a roll-in phase (3 months) that is followed by the actual QIS phase. The remaining clusters follow in month wise steps. The coprimary key performance indicators (KPIs) consist of the ARDS diagnostic rate and guideline adherence regarding lung-protective ventilation. Secondary KPIs include the prevalence of organ dysfunction within 28 days after diagnosis or ICU discharge, the treatment duration on ICU and the hospital mortality. Furthermore, the user acceptance and usability of new technologies in medicine are examined. To show improvements in healthcare of patients with ARDS, differences in primary and secondary KPIs between control phase and QIS will be tested. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent Ethics Committee (EC) at the RWTH Aachen Faculty of Medicine (local EC reference number: EK 102/19) and the respective data protection officer in March 2019. The results of the ASIC QIS will be presented at conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00014330.

The association between change of soluble tumor necrosis factor receptor R1 (sTNF-R1) measurements and cardiovascular and all-cause mortality-Results from the population-based (Cardiovascular Disease, Living and Ageing in Halle) CARLA study 2002-2016.

AIMS: Single measurements of higher levels of soluble tumor necrosis factor receptor I (sTNF-R1) have been shown to be associated with increased risk of mortality. However, up to date, little is known about the underlying temporal dynamics of sTNF-R1 concentrations and their relation with mortality. We aimed to characterize the effect of changes in sTNFR-1 levels on all-cause and cardiovascular mortality, independent from other established risk factors for mortality, including other inflammatory markers. METHODS: We used data of the population based cohort study CARLA and included 1408 subjects with sTNF-R1 measured at baseline (2002-2006) and first follow-up (2007-2010). Cox proportional hazard models were used to assess the association of baseline and follow-up sTNF-R1 measurements with all-cause and cardiovascular mortality during ~10 years since the first follow-up after adjusting for relevant confounders. RESULTS: Based on 211 deaths among 1408 subjects, per each doubling of the baseline sTNF-R1, the risk of all-cause mortality was increased by about 30% (Hazard ratio 1.28, 95% Confidence Interval 0.6-2.7), while per each doubling of the follow-up level of sTNF-R1 mortality was 3-fold (3.11, 1.5-6.5) higher in a model including both measurements and adjusting for confounders. The results were mainly related to the cardiovascular mortality (5.9, 2.1-16.8 per each doubling of follow up sTNF-R1 value). CONCLUSION: Solely the follow-up value, rather than its change from baseline, predicted future mortality. Thus, while sTNF-R1 levels are associated with mortality, particularly cardiovascular, over a long-time period in the general population, if they change, the earlier measurements play no or little role.

Association between advanced glycation end products, their soluble receptor, and mortality in the general population: Results from the CARLA study.

BACKGROUND: Advanced glycation end products (AGEs) in the plasma are associated with a number of age-related diseases that possibly lead to reduced longevity. However, previous studies showed large inconsistencies in the association between AGEs or their soluble receptor (sRAGE) and mortality. We studied this association in a cohort study of general population and assessed the potential changes in this association over time. METHODS: We used data of 958 men and 802 women from the general population in Halle, Germany with a follow up of 12 years. The associations were assessed by means of Kaplan-Meyer survival curves and multivariable and time-varying Cox-regression. RESULTS: AGEs and sRAGE were either not or only weakly (and in the other direction than expected) associated with all-cause mortality after 12 years follow-up in men and women (AGEs: Hazard ratio (HR) = 0.93, 95% confidence interval (95%CI) = 0.83-1.05 for men; HR = 0.88, 95%CI = 0.74-1.05 for women; sRAGE: HR = 1.08, 95%CI = 0.95-1.23 for men; HR = 1.10, 95%CI = 0.92-1.30 for women). There was no change of the predictive values over the follow up time. Sub-analyses with participants with and without AGEs-related conditions (diabetes mellitus and decreased renal function), with age stratified groups (younger (<65 years) and older (≥65 years) participants), with cardiovascular disease mortality as the outcome and the AGE/sRAGE ratio as predictor provided similar results. CONCLUSIONS: Our findings suggest a lack of the expected association with mortality and contribute to the inconsistent findings for plasma-measured AGEs, sRAGE, and AGE/sRAGE ratio.

Metabolically Healthy, but Obese Individuals and Associations with Echocardiographic Parameters and Inflammatory Biomarkers: Results from the CARLA Study.

INTRODUCTION: The research on heterogeneity among obese individuals has identified the metabolically healthy, but obese (MHO) phenotype as a distinct group that does not experience the typical cardiovascular-related diseases (CVD). It is unclear if this group differs with regard to preconditions for CVDs. Our aim was to assess differences in echocardiographic parameters and inflammatory biomarkers between MHO and metabolically healthy, normal weight individuals (MHNW). METHODS: The analyses used data from 1412 elderly participants from a German population-based cohort study (CARLA), which collected detailed information on demographic, biochemical, and echocardiographic variables. Participants were subdivided into four groups (MHNW, MHO, MUNW (metabolically unhealthy, normal weight) and MUO (metabolically unhealthy, obese)) based on BMI≥30 kg/m2 (obese or normal weight) and presence of components of the metabolic syndrome. The clinical characteristics of the 4 groups were compared with ANOVA or Chi-Square test, in addition to two linear regression models for 16 echocardiographic parameters. The difference in inflammatory biomarkers (hsCRP, IL-6 and sTNF-RI) between the groups was examined with a multinomial logistic regression model. RESULTS: The MHO individuals were on average 64.2±8.4 years old, with a higher proportion of women (71.6%), low percentage of smokers, larger waist circumference (109.3±10.5 cm vs 89.1±10.8 cm, p<0.0001) and higher odds ratios for hsCRP, IL-6 and sTNF-RI compared to MHNW individuals. Linear regression models revealed greater left atrial (LA) diameter (2.73 (95% CI: 1.35-4.11) mm), LA volume (7.86 (95% CI: 2.88-12.83) mL), and left ventricular mass index (LVMI) (11.82 (95% CI: 4.43-19.22) g/m1.7) in the MHO group compared to the MHNW group. CONCLUSION: The MHO phenotype is associated with echocardiographic markers of cardiac remodeling (LA diameter, volume and LVMI) and higher odds ratios for inflammatory biomarkers.

Hospital-wide ELectronic medical record evaluated computerised decision support system to improve outcomes of Patients with staphylococcal bloodstream infection (HELP): study protocol for a multicentre stepped-wedge cluster randomised trial.

INTRODUCTION: Staphylococci are the most commonly identified pathogens in bloodstream infections. Identification of Staphylococcus aureus in blood culture (SAB) requires a prompt and adequate clinical management. The detection of coagulase-negative staphylococci (CoNS), however, corresponds to contamination in about 75% of the cases. Nevertheless, antibiotic therapy is often initiated, which contributes to the risk of drug-related side effects. We developed a computerised clinical decision support system (HELP-CDSS) that assists physicians with an appropriate management of patients with Staphylococcus bacteraemia. The CDSS is evaluated using data of the Data Integration Centers (DIC) established at each clinic. DICs transform heterogeneous primary clinical data into an interoperable format, and the HELP-CDSS displays information according to current best evidence in bacteraemia treatment. The overall aim of the HELP-CDSS is a safe but more efficient allocation of infectious diseases specialists and an improved adherence to established guidelines in the treatment of SAB. METHODS AND ANALYSIS: The study is conducted at five German university hospitals and is designed as a stepped-wedge cluster randomised trial. Over the duration of 18 months, 135 wards will change from a control period to the intervention period in a randomised stepwise sequence. The coprimary outcomes are hospital mortality for all patients to establish safety, the 90-day disease reoccurrence-free survival for patients with SAB and the cumulative vancomycin use for patients with CoNS bacteraemia. We will use a closed, hierarchical testing procedure and generalised linear mixed modelling to test for non-inferiority of the CDSS regarding hospital mortality and 90-day disease reoccurrence-free survival and for superiority of the HELP-CDSS regarding cumulative vancomycin use. ETHICS AND DISSEMINATION: The study is approved by the ethics committee of Jena University Hospital and will start at each centre after local approval. Results will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00014320.

Health-Related Disparities among Migrant Children at School Entry in Germany. How does the Definition of Migration Status Matter?

Background: Migration background is known to be an important risk factor for a number of medical outcomes. Still, relatively little is known about the epidemiologic relevance of different definitions of migration status. Methods: Data from 5250 school entry examinations spanning three consecutive years (2015-2017) were gathered from the Public Health Department in Halle, Germany. Data were stratified according to six different migration statuses and evaluated for differences in health service utilization and developmental outcomes. Results: Compared to non-migrant children, migrant children have a lower utilization of preventative services, and higher frequencies of developmental delays. Children with first-generation migration background consistently show results worse than all others, while children with one-sided second-generation migration background show results similar to those of their non-migrant peers. These findings are not substantially altered by adjustment for social status. Conclusions: Children with first-generation migration background should receive special attention in school entry examinations, since they constitute a group with consistently higher health risks compared to other groups of preschoolers.