High-Frequency Heart Rate Variability Is Prospectively Associated With Sleep Complaints in a Healthy Working Cohort.

OBJECTIVE: Vagus nerve functioning, as indexed by high-frequency heart rate variability (HF-HRV), has been implicated in a wide range of mental and physical health conditions, including sleep complaints. This study aimed to test associations between HF-HRV measured during sleep (sleep HF-HRV) and subjective sleep complaints 4 years later. METHODS: One hundred forty-three healthy employees (91% male; MAge = 47.8 years [time 2], SD = 8.3 years) of an industrial company in Southern Germany completed the Jenkins Sleep Problems Scale, participated in a voluntary health assessment, and were given a 24-hour ambulatory heart rate recording device in 2007. Employees returned for a health assessment and completed the Jenkins Sleep Problems Scale 4 years later. RESULTS: Hierarchical regression analyses showed that lower sleep HF-HRV measured in 2007 was associated with higher self-reported sleep complaints 4 years later after controlling for covariates (rab,c = -0.096, b = -0.108, 95% CI, -0.298 to 0.081, ΔR2 = 0.009, p = .050). CONCLUSIONS: These data are the first to show that lower sleep HF-HRV predicted worse sleep 4 years later, highlighting the importance of vagus nerve functioning in adaptability and health.

Assessing adverse childhood experiences in young refugees: a systematic review of available questionnaires.

Today, various questionnaires are available to assess Adverse Childhood Experiences (ACEs) in children; however, it is uncertain if these questionnaires are comprehensive in addressing adversities of vulnerable subgroups, specifically refugee children. This review's objectives are to (1) identify current ACE questionnaires and determine if they are suitable in assessing refugee children's adversities, and (2) identify those previously used within a refugee population. A systematic literature search was conducted across five databases for articles published since 2010, including studies using an ACE-questionnaire that recognized multiple adversities in healthy children and were published in English. A total of 103 ACE questionnaires were identified in 506 studies. Only 14 of the 103 questionnaires addressed a refugee-specific adversity. Their ability to capture refugee children's experiences was limited: available questionnaires used a maximum of three items to assess refugee-specific adversities, covering only a fraction of forms of adversities relevant to refugee children. Psychometric characteristics were rarely reported. In addition, only two ACE questionnaires were used within a refugee population. With the tools currently available, it is not possible to comprehensively assess the exposure to and severity of the adversities faced by refugee children. The perpetuation of ongoing crises necessitates assessing refugee children's adversities to understand how their wellbeing is affected and to identify children at risk.

[Digital health progress hubs-data integration beyond university hospitals]. / Die digitalen Fortschrittshubs Gesundheit ­ Gemeinsame Datennutzung über die Universitätsmedizin hinaus.

The digital health progress hubs pilot the extensibility of the concepts and solutions of the Medical Informatics Initiative to improve regional healthcare and research. The six funded projects address different diseases, areas in regional healthcare, and methods of cross-institutional data linking and use. Despite the diversity of the scenarios and regional conditions, the technical, regulatory, and organizational challenges and barriers that the progress hubs encounter in the actual implementation of the solutions are often similar. This results in some common approaches to solutions, but also in political demands that go beyond the Health Data Utilization Act, which is considered a welcome improvement by the progress hubs.In this article, we present the digital progress hubs and discuss achievements, challenges, and approaches to solutions that enable the shared use of data from university hospitals and non-academic institutions in the healthcare system and can make a sustainable contribution to improving medical care and research.

Development and validation of a self-regulation scale within the German version of the Early Development Instrument.

BACKGROUND: Early childhood self-regulation (SR) is key for many health- and education-related outcomes across the life span. Kindergarten age is a crucial period for SR development, and within this developmental window, potential SR difficulties can still be compensated for (e.g., through interventions). However, efficient measurement of SR through brief, comprehensive, and easy-to-use instruments that identify SR difficulties are scarce. To address this need, we used items of an internationally applied kindergarten teacher questionnaire-the Early Development Instrument (EDI) - to develop and validate a specific SR measurement scale. METHODS: The psychometric evaluation and validation of the selected SR-items was performed in data collected with the German version of the EDI (GEDI), in two independent data sets - (a) the development dataset, with 191 children, and b) the validation dataset, with 184 children. Both included three- to six-year-old children and contained retest and interrater reliability data. First, three independent raters-based on theory-selected items eligible to form a SR scale from the two SR-relevant GEDI domains "social competence" and "emotional maturity". Second, exploratory and confirmatory factor analysis using structural equation modeling examined the item structure across both data sets. This resulted in a defined SR scale, of which internal consistency, test-retest and interrater reliability, cross-validation, and concurrent validity using correlation and descriptive agreements (Bland-Altman (BA) plots) with an existing validated SR-measuring instrument (the Kindergarten Behavioral Scales) were assessed. RESULTS: Confirmatory factor analysis across both data sets yielded the best fit indices with 13 of the GEDI 20 items initially deemed eligible for SR measurement, and a three-factor structure: a) behavioral response inhibition, b) cognitive inhibition, c) selective or focused attention (RMSEA: 0.019, CFI: 0.998). Psychometric evaluation of the resulting 13-item-GEDI-SR scale revealed good internal consistency (0.92), test-retest and interrater reliability (0.85 and 0.71, respectively), validity testing yielded stability across populations and good concurrent validity with the Kindergarten Behavioral Scales (Pearson correlation coefficient: mean 0.72, range 0.61 to 0.84). CONCLUSIONS: The GEDI contains 13 items suitable to assess SR, either as part of regular EDI developmental monitoring or as a valid stand-alone scale. This short 13-item (G)EDI-SR scale may allow early detection of children with SR difficulties in the kindergarten setting in future and could be the basis for public health intervention planning. To attain this goal, future research should establish appropriate reference values using a representative standardization sample.

Perceived importance of pandemic interventions for attending cultural events - findings from Germany.

BACKGROUND: During the first waves of the COVID-19 pandemic, many cultural and sporting events were held without spectators or had to be cancelled. Therefore, several containment strategies to provide requirements for safe events were developed and tested. Nonetheless, every second (50.7%) is afraid of becoming infected on an event. We therefore investigated which hygiene and containment measures are perceived to be important from the visitor's point of view and thus might increase subjective sense of safety. METHODS: This online study was carried out in November 2020. A total of 1,004 persons, who regularly attended events before the pandemic, took part in the study. The importance of different hygiene and containment measures was evaluated using a 5-point Likert-scale (1 "unimportant" to 5 "extremely important"). Potential statistical differences in socio-demographical aspects (age, gender, net disposable income for leisure activities) and attendance on events were tested with analyses of variance. RESULTS: Participants perceived the use of disinfectant (M = 4.10) as the most important element of containment strategies, followed by transparent information on the hygiene strategy (M = 4.00), reduced occupancy (M = 3.98), and optimized ventilation (M = 3.97). Body temperature measurement at the entrance (M = 3.27), a negative SARS-CoV-2 test (M = 3.11), completion of a health questionnaire (M = 3.05), and abandoning breaks and catering (M = 2.98) were considered as less important. Analyses of group differences in socio-demographical aspects found abandoning breaks and catering to be more important to men than to women. This strategy is also more important to people aged 66 and above than to younger age groups (e.g., age 20-40). For women, the use of disinfectant is considerably more important. No other significant differences exist. CONCLUSION: Combining relevant measures appears to be important to provide a safe containment strategy. Measures aimed at positively influencing people's sense of safety do not fully correspond to researched knowledge of effectiveness. There are also target group-specific differences in the rating of measures, which should be considered while preparing containment strategies. To describe the dynamic development of changes in subjective rating of containment strategies, continuing research is needed.

Stress at work is associated with intima media thickness in older male employees, independent of other sources of stress perception.

Chronic stress at work shows a moderate but robust longitudinal association with cardiovascular disease (CVD). Atherosclerosis is a pathophysiological process of most CVD, for which intima media thickness (IMT) of the carotid artery is used as an early marker. Its relationship with stress at work has remained largely unexplored, and the present study therefore aimed to elucidate the association between stress at work, assessed as effort-reward imbalance (ERI), and IMT. This cross-sectional study comprised of 501 male German employees aged 42 (19-64) years at enrollment into the Mannheim Industrial Cohort Study. Clinical assessments used fasting blood samples and IMT measurement. Self-report questionnaires assessed sources of perceived stress. Analyses adjusted for medical history, life style, and socio-economic status (SES) indicators as well as general perceived stress and worries to determine the specificity of ERI. Linear regression models estimated the association of ERI with IMT, stratifying for age groups and adjusting for potential confounders. ERI ratio increased until the age of 50 years and abated thereafter. In participants younger than 50 years IMT measurements were not associated with ERI ratios. However, despite lower mean ERI ratios in participants older than 50 years, this age group showed a significant relationship with IMT (standardized Beta = .36, p < .01), adjusting for multiple confounders including general perceived stress and worries. These analyses suggest that atherosclerosis in older employees is specifically related to stress at work. Longitudinal studies will help to elucidate the temporal relationship between stress exposure and downstream biological mechanisms.Lay summaryOur study explored the association of job stress and the calcification of the carotid artery in German employees. We found out that this association is stronger in employees older than 50 years. In addition, it is independent of medical risk factors and stress caused by private issues.

Robust nanoscopy of a synaptic protein in living mice by organic-fluorophore labeling.

Extending superresolution fluorescence microscopy to living animals has remained a challenging frontier ever since the first demonstration of STED (stimulated emission depletion) nanoscopy in the mouse visual cortex. The use of fluorescent proteins (FPs) in in vivo STED analyses has been limiting available fluorescence photon budgets and attainable image contrasts, in particular for far-red FPs. This has so far precluded the definition of subtle details in protein arrangements at sufficient signal-to-noise ratio. Furthermore, imaging with longer wavelengths holds promise for reducing photostress. Here, we demonstrate that a strategy based on enzymatic self-labeling of the HaloTag fusion protein by high-performance synthetic fluorophore labels provides a robust avenue to superior in vivo analysis with STED nanoscopy in the far-red spectral range. We illustrate our approach by mapping the nanoscale distributions of the abundant scaffolding protein PSD95 at the postsynaptic membrane of excitatory synapses in living mice. With silicon-rhodamine as the reporter fluorophore, we present imaging with high contrast and low background down to ∼70-nm lateral resolution in the visual cortex at ≤25-µm depth. This approach allowed us to identify and characterize the diversity of PSD95 scaffolds in vivo. Besides small round/ovoid shapes, a substantial fraction of scaffolds exhibited a much more complex spatial organization. This highly inhomogeneous, spatially extended PSD95 distribution within the disk-like postsynaptic density, featuring intricate perforations, has not been highlighted in cell- or tissue-culture experiments. Importantly, covisualization of the corresponding spine morphologies enabled us to contextualize the diverse PSD95 patterns within synapses of different orientations and sizes.

Measures of infection prevention and incidence of SARS-CoV-2 infections in cancer patients undergoing radiotherapy in Germany, Austria and Switzerland.

PURPOSE: COVID-19 infection has manifested as a major threat to both patients and healthcare providers around the world. Radiation oncology institutions (ROI) deliver a major component of cancer treatment, with protocols that might span over several weeks, with the result of increasing susceptibility to COVID-19 infection and presenting with a more severe clinical course when compared with the general population. The aim of this manuscript is to investigate the impact of ROI protocols and performance on daily practice in the high-risk cancer patients during this pandemic. METHODS: We addressed the incidence of positive COVID-19 cases in both patients and health care workers (HCW), in addition to the protective measures adopted in ROIs in Germany, Austria and Switzerland using a specific questionnaire. RESULTS: The results of the questionnaire showed that a noteworthy number of ROIs were able to complete treatment in SARS-CoV­2 positive cancer patients, with only a short interruption. The ROIs reported a significant decrease in patient volume that was not impacted by the circumambient disease incidence, the type of ROI or the occurrence of positive cases. Of the ROIs 16.5% also reported infected HCWs. About half of the ROIs (50.5%) adopted a screening program for patients whereas only 23.3% also screened their HCWs. The range of protective measures included the creation of working groups, instituting home office work and protection with face masks. Regarding the therapeutic options offered, curative procedures were performed with either unchanged or moderately decreased schedules, whereas palliative or benign radiotherapy procedures were more often shortened. Most ROIs postponed or cancelled radiation treatment for benign indications (88.1%). The occurrence of SARS-CoV­2 infections did not affect the treatment options for curative procedures. Non-university-based ROIs seemed to be more willing to change their treatment options for curative and palliative cases than university-based ROIs. CONCLUSION: Most ROIs reported a deep impact of SARS-CoV­2 infections on their work routine. Modification and prioritization of treatment regimens and the application of protective measures preserved a well-functioning radiation oncology service and patient care.

Psychometric properties and contextual appropriateness of the German version of the Early Development Instrument.

BACKGROUND: Assessing the early development of children at a population level in educational settings, may be useful for public health and policy decision making. In this study, we evaluated the psychometric properties and the contextual appropriateness of a German language version of the Early Development Instrument (EDI), a survey-based instrument originally developed in Canada, which assesses developmental vulnerability for children in preschool settings. METHODS: Sixty preschool teachers from six preschool organizations (22% of organizations contacted) in three cities in southwest Germany participated. They administered a German version of the EDI (GEDI) to 225 children (51% of eligible children). We assessed internal consistency, test-retest and interrater reliability. Preschool teachers assisted in determining face-validity by reviewing item coverage and comprehensibility. Exploratory factor analysis (EFA) was used to evaluate convergent validity. Concurrent validity was measured using correlations and agreements (Bland-Altman plots) between GEDI and other validated instrument scores. Additionally, we compared associations between GEDI domain scores and sociodemographic characteristics with similar associations in EDI studies worldwide. RESULTS: GEDI domains showed good to excellent internal consistency (0.73 < α > 0.99) and moderate to good test-retest and interrater reliability (0.50 to 0.81 and 0.48 to 0.71, respectively [p-value < 0.05]). Face validity was considered acceptable. EFA showed a factor structure similar to the original EDI. Correlations (range: 0.32 to 0.67) and agreements between GEDI scores and other German language instruments suggested good external reliability. Scoring within the lowest 10th percentile was strongly associated with age. CONCLUSIONS: Our psychometric assessment suggests good reliability and consistency of the GEDI. Differences in the age distribution of children, pedagogical objectives and educational system features of German preschools require future work to determine score thresholds indicative of vulnerability. Aside from dropping selected items from the original EDI that were inconsistent with features of the German educational system, the distribution of values in the language and cognitive development domain also suggested that context-specific cut-offs must be established for the German version. Such efforts are needed to account for relevant contextual differences between the educational systems.

Associations of Changes in Organizational Justice with Job Attitudes and Health-Findings from a Prospective Study Using a Matching-Based Difference-in-Difference Approach.

BACKGROUND: Ample evidence indicates that unfairness at the workplace (organizational injustice) is associated with both job attitudes and health of employees. Several factors that influence these associations have been identified: e.g., personality traits, such as the Big Five traits, justice sensitivity, type of occupation (e.g., white-collar), and unobserved time-invariant factors. Previous studies only addressed parts of these issues, and the ideal research design to mitigate biases-an experiment with random assignment to a treatment and control group-is not feasible. This study therefore mimics a randomized experiment using two statistical techniques. METHODS: First, matching was implemented to balance the treatment and control group in confounding factors (demographics and personality) in two prospective waves (2012-2014) of observational data (4522 white-collar, 2984 blue-collar) taken from the Linked Personnel Panel, which is an employee survey representative for German private sector companies with more than 50 employees. Second, a difference-in-difference approach excludes unobserved time-invariant factors by estimating associations of changes in organizational justice (distributive, procedural, interactional) with job attitudes (job satisfaction, turnover intention) and health (general and mental) in these groups, separate for white- and blue-collar employees. RESULTS: A decrease in perceived justice was associated with lower job attitudes (less job satisfaction and higher turnover intentions), while an increase was associated with higher values. This pattern was found for white- and blue-collar workers and also for health indicators, with the latter, however, being less pronounced. CONCLUSIONS: Increased fairness at the workplace is related to better job attitudes and health for white- and blue-collar employees, independent of personality traits and unobserved time-invariant factors.

Prevalence and predictors of dropout from high-intensity interval training in sedentary individuals: A meta-analysis.

Recent evidence suggests that high-intensity interval training (HIIT) is an effective method to improve fitness and various health markers. However, the tolerability and acceptability of HIIT among sedentary individuals is currently controversially discussed. Therefore, our objective was to investigate the prevalence and predictors of dropout among sedentary individuals in HIIT-based exercise interventions. MEDLINE/PubMed, SPORTDiscus, and Web of Science were searched systematically for relevant articles until 06/2018. Studies included were required to (a) be written in English, (b) include sedentary healthy adults, (c) use some form of HIIT without any complementary intervention, (d) last ≥4 weeks, (e) report detailed description of the applied HIIT protocol, and (f) report data that allow calculation of a dropout rate. Fifty-five studies reporting results from 67 HIIT interventions with 1318 participants met the eligibility criteria. The trim and fill adjusted pooled dropout rate across all interventions was 17.6% (95% confidence interval 14.2-21.5%). Dropout rates were significantly lower in cycling-based interventions compared with studies using running/walking as exercise modality (P < 0.001). Longer session time (ß = 0.02, P < 0.05), higher time effort/week (ß = 0.005, P < 0.05), and overall time effort/intervention (ß = 0.0003, P < 0.05) predicted greater dropout. Exercise intensity was not related to dropout. Our data suggest that HIIT-based interventions are tolerable and acceptable for previously sedentary individuals, exhibiting generally lower dropout rates than commonly reported for traditional exercise programs. Given the association between HIIT volume and dropouts, future studies should further focus on identifying the minimally effective dose of practical HIIT for improving health status. Such efforts would be important to increase implementation and public health impact of HIIT.

Identification of starting points to promote health and wellbeing at the community level - a qualitative study.

BACKGROUND: As health is influenced by the social, economic and environmental conditions in which individuals live, local communities are an ideal setting to promote health and wellbeing. However, up to now various health promotion interventions at the community level have had limited success, perhaps related to an incomplete understanding of local contexts and priorities. We therefore aimed to develop a broader and deeper understanding of topics or issues that were most salient to residents of a South-West German community by exploring their perceptions of needs, challenges, barriers and existing resources related to health and well-being. METHODS: As an initial step of a multi-year community-based participatory research project, we conducted semi-structured interviews with key informants (n = 30) from various community settings (e.g., child care, elderly care, businesses, non-profit organizations, village councils, and local government). The terms "health" and "wellbeing" were included in the stem of each question in the semi-structured interview guide to enable a focus on related perceived needs, challenges, barriers and existing resources. Interviews were audiotaped, transcribed verbatim and analyzed using qualitative content analysis techniques. RESULTS: Themes emerging from our interviews appeared to center primarily in three distinct areas: natural resources and built environment, access to services, and social cohesion including subthemes on the importance of social engagement and volunteerism, sense of community, and shared identity. CONCLUSIONS: That health and wellbeing were not identified explicitly as a priority by key informants suggests that these should not be presented as the primary focus of a community-wide initiative. Instead themes with a higher priority should be addressed in ways that can lead to better health and wellbeing as a secondary goal.

Associations of ambivalent leadership with distress and cortisol secretion.

Ambivalent social ties, i.e., whereby a relationship is evaluated simultaneously in positive and negative terms, are a potential source of distress and can perturb health-relevant biological functions. Social interactions at the workplace, in particular with supervisors, are often described in ambivalent terms, but the psychological and psychobiological impact of such interactions has received little scientific attention. The current study examined associations between ambivalent attitudes towards one's supervisor, perceived distress (general and work-related), and diurnal dynamics of the stress hormone cortisol. 613 employees evaluated their supervisor in terms of positive and negative behaviors, which was combined into an ambivalent index. Higher ambivalence was associated with higher perceived distress and work-related stress (p < .001), and with a larger cortisol awakening response and higher day-time secretion post-awakening (p < .01). The present study is the first to identify ambivalence towards supervisors as a predictor of employee distress and stress-related endocrine dysregulation. In consequence, focusing solely on positive or negative leader behavior may insufficiently capture the true complexity of workplace interactions and attempts to compensate negative behaviors with positive are unlikely to reduce distress-but quite the opposite-by increasing ambivalence.

Effects of low-volume high-intensity interval training in a community setting: a pilot study.

PURPOSE: High-intensity interval training (HIIT) is emerging as an effective and time-efficient exercise strategy for health promotion. However, most HIIT studies are conducted in laboratory settings and evidence regarding the efficacy of time-efficient "low-volume" HIIT is based mainly on demanding "all-out" protocols. Thus, the aim of this pilot study was to assess the feasibility and efficacy of two low-volume (≤ 30 min time-effort/week), non-all-out HIIT protocols, performed 2 ×/week over 8 weeks in a community-based fitness centre. METHODS: Thirty-four sedentary men and women were randomised to either 2 × 4-min HIIT (2 × 4-HIIT) or 5 × 1-min HIIT (5 × 1-HIIT) at 85-95% maximal heart rate (HRmax), or an active control group performing moderate-intensity continuous training (MICT, 76 min/week) at 65-75% HRmax. RESULTS: The exercise protocols were well tolerated and no adverse events occurred. 2 × 4-HIIT and 5 × 1-HIIT exhibited lower dropout rates (17 and 8 vs. 30%) than MICT. All training modes improved VO2max (2 × 4-HIIT: + 20%, P < 0.01; 5 × 1-HIIT: + 27%, P < 0.001; MICT: + 16%, P < 0.05), but the HIIT protocols required 60% less time commitment. Both HIIT protocols and MICT had positive impact on cholesterol profiles. Only 5 × 1-HIIT significantly improved waist circumference (P < 0.05) and subjective work ability (P < 0.05). CONCLUSIONS: The present study indicates that low-volume HIIT can be feasibly implemented in a community-based setting. Moreover, our data suggest that practical (non-all-out) HIIT that requires as little as 30 min/week, either performed as 2 × 4-HIIT or 5 × 1-HIIT, may induce significant improvements in VO2max and cardiometabolic risk markers.

Contextual influences on physical activity and eating habits -options for action on the community level.

BACKGROUND: This conceptual paper aims to illustrate the ways in which communities are able to advance health improvements on a population level. Outcome measures may include increased physical activity and healthier eating habits in particular, as well as an improved health-related quality of life and social cohesion as more generic outcomes. MAIN BODY: The paper begins by asking initial questions: Why did previous health-specific interventions only show moderate effects on an individual level and mixed effects on a population level? What is the added value of a community-based public health perspective compared to the traditional biomedical perspective when it comes to prevention? Why are we living the way we are living? Why do we eat what we eat? Why do we move the way we move? Subsequently, we illustrate the broad spectrum of contextual interventions available to communities. These can have geographical and technological as well as economic, political, normative and attitude-specific dimensions. It is shown that communities have a strong influence on health-related contexts and decision-making of adults, adolescents and children. In addition contextual characteristics, effects, mediators, moderators and consequences relevant for health can differ greatly between age groups. Both small-scale settings and overarching sectors possess physical, economic, political and sociocultural characteristics that can be proactively influenced by community decision-makers in the sense of a "health in all policies"-strategy. SHORT CONCLUSION: After presenting various interdisciplinary approaches to community-based health interventions, the manuscript closes with the following core message: Successful community-based health promotion strategies consist of multilevel - multicomponent interventions on the micro, meso and macro-level-environments.

Applied immuno-epidemiological research: an approach for integrating existing knowledge into the statistical analysis of multiple immune markers.

BACKGROUND: Immunologists often measure several correlated immunological markers, such as concentrations of different cytokines produced by different immune cells and/or measured under different conditions, to draw insights from complex immunological mechanisms. Although there have been recent methodological efforts to improve the statistical analysis of immunological data, a framework is still needed for the simultaneous analysis of multiple, often correlated, immune markers. This framework would allow the immunologists' hypotheses about the underlying biological mechanisms to be integrated. RESULTS: We present an analytical approach for statistical analysis of correlated immune markers, such as those commonly collected in modern immuno-epidemiological studies. We demonstrate i) how to deal with interdependencies among multiple measurements of the same immune marker, ii) how to analyse association patterns among different markers, iii) how to aggregate different measures and/or markers to immunological summary scores, iv) how to model the inter-relationships among these scores, and v) how to use these scores in epidemiological association analyses. We illustrate the application of our approach to multiple cytokine measurements from 818 children enrolled in a large immuno-epidemiological study (SCAALA Salvador), which aimed to quantify the major immunological mechanisms underlying atopic diseases or asthma. We demonstrate how to aggregate systematically the information captured in multiple cytokine measurements to immunological summary scores aimed at reflecting the presumed underlying immunological mechanisms (Th1/Th2 balance and immune regulatory network). We show how these aggregated immune scores can be used as predictors in regression models with outcomes of immunological studies (e.g. specific IgE) and compare the results to those obtained by a traditional multivariate regression approach. CONCLUSION: The proposed analytical approach may be especially useful to quantify complex immune responses in immuno-epidemiological studies, where investigators examine the relationship among epidemiological patterns, immune response, and disease outcomes.

The streamlined Allostatic Load Index: a replication of study results.

According to the World Health Organization stress in the workplace is becoming a major challenge of employers worldwide. While perceived stress levels can be assessed by questionnaires there is growing evidence that stress-related wear and tear of our body can be measured by the Allostatic Load Index (ALI). In a sample of 12,477 German industrial employees (19.6% female, 18-65 years) self-rated stress was explored by the effort-reward imbalance (ERI) questionnaire. A voluntary health check included biomarkers such as diastolic blood pressure, waist circumference, glycosylated hemoglobin, low-density lipoprotein, and heart rate variability. Based on predefined subclinical cutoff values, a 5-variable ALI was calculated. Differences in ALI according to low (ERI ≤1.0) and high (ERI >1.0) stress levels were tested. The association of ERI and ALI was explored using logistic regression analysis controlling for multiple confounders. Employees perceiving high stress levels showed significant higher ALI scores (p < .001) compared to lower stressed employees. This association was stronger in men and independent of age. ALI was associated with work stress in adjusted models (OR 1.18 ± .08 [95% CI 1.03, 1.36]; p < .05). This study replicates former results in a large sample of industrial employees indicating that work stress is associated with a short form ALI.

Determinants of peripapillary retinal nerve fiber layer thickness regarding ocular and systemic parameters - the MIPH Eye&Health Study.

BACKGROUND: Optical coherence tomography (OCT) allows quantitative image analysis of retinal tissue in vivo. Peripapillary retinal nerve fiber layer (pRNFL) thickness is widely used for evaluation of retinal nerve fiber rarefaction in several optic neuropathies. This study evaluates associations of pRNFL thickness in healthy adult subjects in order to evaluate influencing factors. METHODS: A cross-sectional study was performed in a working-age population. Only eyes without detectable ocular pathologies were included in the analysis. Among analyzed systemic cardiovascular parameters were age, gender, body-mass index, mean arterial blood pressure, HbA1c, high- and low-density-lipoproteins, and triglycerides. A comprehensive ophthalmological examination including refraction, tonometry, keratometry, and central corneal thickness measurmentwas performed. In addition, pRNFL thickness was imaged by spectral-domain OCT. Univariable and multivariable associations of pRNFL thickness in all four quadrants and on average with systemic and ocular parameters were calculated using a generalized estimating equation model. RESULTS: Three hundred and six subjects were included. pRNFL thickness measurements showed a significant association with spherical equivalent: pRNFL thickness decreased with increasing myopia in all quadrants (multivariable regression coefficients Beta: superior: 1.16, 95 % CI [0.62;1.71], p < 0.001; temporal: 0.87, [0.33;1.41], p = 0.001; inferior: 1.80, [1.18;2.42], p < 0.001; nasal: 2.60, [2.01;3.20], p < 0.001) and on average (1.51, [1.20;1.82], p < 0.001). A thicker central cornea thickness was related to lower pRNFL in the superior (-0.05, [-0.10; -0.01], p = 0.01), the inferior quadrant (-0.05, [-0.10;0.00], p = 0.03) and on average (-0.04, [-0.07; -0.01], p = 0.02). All other parameters were not  associated. CONCLUSION: Our findings highlight the importance of refraction when evaluating pRNFL thickness and its independence from other systemic parameters.

"Drug-Survival"-Raten und Gründe für den Abbruch von Systemtherapien bei Psoriasis.

HINTERGRUND UND ZIELE: Mittelschwere bis schwere Psoriasis erfordert häufig eine langfristige systemische Behandlung. Die Therapietreue bezüglich eines Medika-ments (Überlebensrate, "Drug Survival") reflektiert dessen Wirksamkeit, Sicherheit sowie die Zufriedenheit mit der Behandlung und ist ein Indikator für den Therapieerfolg. Das Ziel der vorliegenden Studie was die Ermittlung der "Drug-Survival"-Raten sowie der Gründe für den Abbruch einer Behandlung mit Fumarsäureestern (fumaric acid esters, FAE), Methotrexat (MTX), Acitretin (ACI), Cyclosporin A (CyA), Adalimumab (ADA), Etanercept (ETA), Infliximab (INF) und Ustekinumab (UST) bei Patienten mit mittelschwerer bis schwerer Psoriasis. PATIENTEN UND METHODEN: Wir führten eine retrospektive Analyse an 373 Patienten durch, die im Zeitraum 1/2003-5/2014 insgesamt 696 Behandlungen an einem deutschen Universitätsklinikum erhalten hatten. ERGEBNISSE: Die unbereinigte Überlebenswahrscheinlichkeit war für UST am höchsten, gefolgt von ADA, ETA, INF, FAE, MTX, ACI und CyA. In der multivariaten Regressionsanalyse mit FAE als Referenz betrug die Hazard Ratio (HR) für einen Abbruch 0,14 (95 % Konfidenzintervall: 0,06-0,35) bei UST, 0,43 (0,26-0,73) bei ADA, 2,11 (1,14-3,91) bei ACI und 3,26 (1,44-7,39) bei CyA. Das "Drug Survival" von INF war länger, wenn es in Kombination mit MTX eingesetzt wurde (HR 2,87; 1,21-6,81). Traditionelle systemische Antipsoriatika sowie INF wurden am häufigsten aufgrund von Nebenwirkungen abgesetzt; alle anderen Biologika aufgrund ihrer Unwirksamkeit für kutane Psoriasis-Läsionen. SCHLUSSFOLGERUNGEN: "Drug-Survival"-Raten sollten bei der Therapieentscheidung berücksichtigt werden, um den Patienten eine bestmögliche Langzeitstrategie zu bieten.

Drug survival rates and reasons for drug discontinuation in psoriasis.

BACKGROUND AND OBJECTIVES: Moderate-to-severe psoriasis frequently requires long-term systemic therapy. Reflecting efficacy, safety, and treatment satisfaction, drug survival is an indicator of therapeutic success. The objective of the present study was to assess drug survival rates and reasons for discontinuation of fumaric acid esters (FAE), methotrexate (MTX), acitretin (ACI), cyclosporine A (CyA), adalimumab (ADA), etanercept (ETA), infliximab (INF), and ustekinumab (UST) in patients with moderate-to-severe psoriasis. PATIENTS AND METHODS: We performed a retrospective analysis of 373 patients who had received a total of 696 treatment courses at a German university hospital in the period 1/2003-5/2014. RESULTS: The crude probability of survival was highest for UST, followed by ADA, ETA, INF, FAE, MTX, ACI, and CyA. In multivariate regression analysis using FAE as reference, hazard ratios (HR) for discontinuation were 0.14 (95 % confidence interval: 0.06-0.35) for UST, 0.43 (0.26-0.73) for ADA, 2.11 (1.14-3.91) for ACI, and 3.26 (1.44-7.39) for CyA. INF showed longer survival when combined with MTX (HR 2.87, 1.21-6.81). Traditional systemic antipsoriatic agents as well as INF were most frequently discontinued due to adverse events; all other biologics, due to inefficacy with respect to cutaneous lesions. CONCLUSIONS: Drug survival rates should be integrated into therapeutic decisions in order to provide patients with an optimal long-term strategy.