Obesity is linked to disease severity in moderate to severe atopic dermatitis-Data from the prospective observational TREATgermany registry.

BACKGROUND: There are conflicting data on a potential association between obesity and atopic dermatitis (AD). The purpose of this study was to investigate the relationship between obesity and AD disease severity. METHODS: Patients from the TREATgermany registry cohort were divided into three groups according to their body mass index (BMI). Due to low numbers, underweight patients (BMI <18.5 kg/m2) were excluded from the analysis. Physician- and patient-reported disease severity scores as well as additional phenotypic characteristics were evaluated for association with BMI. Generalized linear mixed models and multinomial logit models, respectively, were applied to investigate the association of BMI, age, sex and current systemic AD treatment with disease severity. RESULTS: This study encompassed 1416 patients, of which 234 (16.5%) were obese (BMI ≥30 kg/m2). Obesity was associated with lower educational background and smoking. Otherwise, obese and non-obese AD patients had similar baseline characteristics. Increased BMI was associated with higher oSCORAD (adjusted ß: 1.24, 95% CI: 1.05-1.46, p = 0.013) and Patient-oriented eczema measure (POEM) (adjusted ß: 1.09, 95% CI: 1.01-1.17, p = 0.038). However, the absolute difference in the overall oSCORAD was small between obese and non-obese AD patients (Δ oSCORAD = 2.5). Allergic comorbidity was comparable between all three groups, with the exception of asthma which was more pronounced in obese patients (p < 0.001). DISCUSSION: In this large and well-characterized AD patient cohort, obesity is significantly associated with physician- and patient-assessed measures of AD disease severity. However, the corresponding effect sizes were low and of questionable clinical relevance. The overall prevalence of obesity among the German AD patients was lower than in studies on other AD cohorts from different countries, which confirms previous research on the German population and suggests regional differences in the interdependence of AD and obesity prevalence.

High recurrence rate of eczema herpeticum in moderate/severe atopic dermatitis -TREATgermany registry analysis.

BACKGROUND: Eczema herpeticum (EH) is a disseminated skin infection caused by herpes simplex virus in atopic dermatitis (AD) patients. The frequency of EH and the clinical features of EH patients have not yet been investigated in a larger cohort. METHODS: We sought to investigate the TREATgermany cohort, a multicenter, non-interventional clinical registry of moderately to severely affected AD patients in Germany. Baseline characteristics of patients included between December 2017 and April 2021 were compared between patients without, single, and multiple EH. RESULTS: Of the 893 patients, 195 (21.8%) had at least one EH. Of the 195 patients with EH, 107 had multiple EH (54.9%), representing 12.0% of the total study population. While there were no differences in demographic characteristics, previous treatment, and disease scores at enrollment (itch, IGA, oSCORAD, EASI), patients with EH had more frequent atopic comorbidities and sensitizations to house dust mite, food, and mold. DISCUSSION: TREATgermany registry data suggest a high prevalence and recurrence rate of EH, while there appears to be no specific clinical phenotype, besides an increase in allergies, to identify EH patients in the daily routine.

Itch, sleep loss, depressive symptoms, fatigue, and productivity loss in patients with moderate-to-severe atopic dermatitis: Analyses of TREATgermany registry data.

BACKGROUND: TREATgermany is a multicenter registry including patients with moderate-to-severe atopic dermatitis (AD) from currently 74 study centers (university clinics, hospitals and practices) in Germany. As of August 31, 2021, 1,230 adult patients were enrolled. METHODS: In TREATgermany, patients and physicians fill in questionnaires pertaining to symptoms, disease severity, quality of life, depressiveness, and fatigue. In particular, limitations in work performance are assessed using the Work Limitations Questionnaire (WLQ). To assess associations between occupational performance/work limitations and symptoms, correlations and regression models were calculated. RESULTS: The examined sample of 228 employed patients reported an average of 6% at-work productivity loss within the past two weeks prior to enrolment in the registry. The WLQ productivity loss score was moderately associated with itch (r = 0.32) and sleep loss (r = 0.39) and strongly associated with depressive symptoms (r = 0.68) and fatigue (r = 0.60). CONCLUSIONS: The analyses of the registry data show that moderate-to-severe atopic dermatitis has a negative impact on the work productivity of the patients. The analyses further point out the relevant associations between work productivity, depressive symptoms, and fatigue highlighting the disease burden caused by the psychological components of AD.

Itching in Atopic Dermatitis: Patient- and Physician-reported Outcomes in the German Atopic Dermatitis Registry TREATgermany.

TREATgermany is an investigator-initiated prospective disease registry. It investigates physician- and patient-reported disease severity (Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator Global Assessment, Patient-Oriented Eczema Measure (POEM), Patient Global Assessment (PGA)), patient-reported symptoms (itch, sleep loss, depressive symptoms), therapy courses and dermatological quality of life (DLQI) in moderate-to-severe atopic dermatitis with SCORAD > 20. 1,134 atopic dermatitis patients (mean age 41.0 ± 14.7 years, 42.5% females) were enrolled by 40 German recruiting sites (dermatological clinics and practices) between June 2016 and April 2021. The current analysis focuses on itch scores obtained with a numerical rating scale (NRS)) documented for the previous 3 days prior to baseline visit. The results show that 97.2% (1,090 of 1,121) patients experienced itch. Itch severity correlated moderately with severity of atopic dermatitis oSCORAD (rho = 0.44 (0.39-0.48)) and EASI score (rho = 0.41 (0.36-0.46)). A strong correlation was found with self-reported disease severity as PGA (rho = 0.68 (0.65-0.71)), POEM sum score (rho = 0.66 (0.63-0.69)) and dermatological quality of life impairment DLQI (rho = 0.61 (0.57-0.65)). Itch as a subjective complaint is more closely correlated with patient-reported outcomes than with objective assessments by the physician.

Real-world data on the effectiveness, safety and drug survival of dupilumab: an analysis from the TREATgermany registry.

This interim analysis from the atopic dermatitis registry TREATgermany shows robust long-term efficacy, favourable safety and high persistence of dupilumab under real life conditions.

Prediction of inpatient pressure ulcers based on routine healthcare data using machine learning methodology.

Despite the relevance of pressure ulcers (PU) in inpatient care, the predictive power and role of care-related risk factors (e.g. anesthesia) remain unclear. We investigated the predictability of PU incidence and its association with multiple care variables. We included all somatic cases between 2014 and 2018 with length of stay ≥ 2d in a German university hospital. For regression analyses and prediction we used Bayesian Additive Regression Trees (BART) as nonparametric modeling approach. To assess predictive accuracy, we compared BART, random forest, logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) using area under the curve (AUC), confusion matrices and multiple indicators of predictive performance (e.g. sensitivity, specificity, F1, positive/ negative predictive value) in the full dataset and subgroups. Analysing 149,006 cases revealed high predictive variable importance and associations between incident PU and ventilation, age, anesthesia (≥ 1 h) and number of care-involved wards. Despite high AUCs (range 0.89-0.90), many false negative predictions led to low sensitivity (range 0.04-0.10). Ventilation, age, anesthesia and number of care-involved wards were associated with incident PU. Using anesthesia as a proxy for immobility, an hourly repositioning is indicated. The low sensitivity indicates major challenges for correctly predicting PU based on routine data.

Status report on the atopic dermatitis registry TREATgermany.

BACKGROUND: The TREATgermany registry collects data from children, adolescents, and adults with moderate-to-severe atopic dermatitis (AD) in Germany. For this purpose, clinical and patient-reported outcomes, the course of the disease, and applied therapies are observed. METHODS: TREATgermany recruits patients with moderate-to-severe AD according to the diagnostic criteria of the UK Working Party, an "Objective Scoring for Atopic Dermatitis" (oSCORAD) > 20 and/or currently antiinflammatory systemic treatment for AD or previous anti-inflammatory systemic treatment for AD within past 24 months before inclusion. No study related interventions will be performed. Currently, 59 dermatological practices, clinics, and university hospitals are participating in TREATgermany (as of May 2021). Based on the interim analysis of October 13, 2020, patient characteristics were described from 4,373 documented visits of adult participants (n = 1,025). RESULTS: The mean age at inclusion in TREATgermany was 42 years, 57.7% of patients were men (n = 591) and 42.3% were women (n = 434). According to oSCORAD, 85.8% of those included suffered from moderate-to-severe AD. At baseline visit, 744 patients had already received one or more systemic treatments for AD (glucocorticosteroids n = 600, ciclosporin A (CSA) n = 307, dupilumab n = 98). 597 patients received dupilumab during their participation in TREATgermany, 134 patients received CSA. CONCLUSION: With the increasing number of recruitment centers (October 2020: 38 centers; May 2021: 59 centers), TREATgermany can continue to make an important contribution to health services research for patients with moderate-to-severe AD. The registry fulfills the methodological requirements of IQWiG for the collection and processing of healthcare-related data. With the successful and expected approval of further systemic treatments, these can be compared in terms of efficacy and safety in the future. In addition, with the recruitment of children and adolescents started in 2021, this patient group can also be observed.

[Association between Socioeconomic Status and Developmental Status: Data Linkage of Results of the Daycare and School Entry Health Examinations of a Saxon Birth Cohort Study]. / Zusammenhang zwischen sozioökonomischem Status und Entwicklungsstand ­ Datenlinkage von Ergebnissen der Kita- und Schulaufnahmeuntersuchung mit einer sächsischen Geburtskohortenstudie.

BACKGROUND: Child development is determined by both biological (e. g. gender, natal maturity) and psychosocial (e. g. socioeconomic status, daycare) factors. OBJECTIVES: To examine how familial socioeconomic status (SES) as well as biological and other psychosocial factors are associated with the state of development of 4- and 6-year-old children. METHODS: Data linkage of primary data from a birth cohort study and routine data from the Saxon public health departments on children born between 2007 and 2008, who underwent both daycare health examination and school entry health examination (N=615), was used to examine speech and motor skills, both fine and gross, for associations with psychosocial and biological factors. Potential associations were tested for significance and shown as odds ratios by using binary logistic regression. RESULTS: There were no noticeable problems in the development of the majority of Saxon children until school entry. Nevertheless, language seems to be a sensitive area of development, since 37% of the children showed problems at both time-points. Furthermore boys, preterm infants and children from a lower socio-economic class were more often affected by developmental delays, with preterm infants with low SES being at very high risk. Furthermore, the point of time of entering daycare seems to be of relevance for child development. CONCLUSIONS: The results are in line with national and international findings. An important new finding is the significantly increased likelihood of having developmental problems when biological and psychosocial risk factors coincide. However, longitudinal analyses are required to study developmental courses and to evaluate measures initiated to combat these issues.

Individual-Level Linkage of Primary and Secondary Data from Three Sources for Comprehensive Analyses of Low Birthweight Effects.

AIM OF THE STUDY: The linkage of primary and secondary data is becoming an increasingly popular approach in healthcare research, but involves some challenges for all involved parties, for example due to data protection requirements. The aim of this article is to systematically outline the methods used and experiences made during a cohort study in the field of pediatric health care research (EcoCare-PIn) that involved access to and linkage of three different data sources. Particular focus is placed on the necessary regulatory measures with regard to data access and data linkage as well as on data validation to ensure a correct linkage. METHODS: While complying with all relevant data protection requirements, the study realized an individual-level linkage of a) pseudonymized administrative health insurance data from a statutory health insurance on Saxon children born between 2007 and 2013, b) primary data collected via postal questionnaires from parents/caregivers and c) medical data from kindergarten- and school-entry-examinations of Saxon health authorities. The fundamental principle of the concept of data linkage was to strictly separate the sites of data collection and data analysis, which was realized through the involvement of a trust center. RESULTS: Challenges especially pertained to the extensive regulatory pre-requirements for data access as well as to data protection requirements while performing the study. Technical aspects and data validation also required a considerable share of attention and resources. A number of validation routines were applied to avoid incorrect data linkage and to ensure the high quality of the final dataset. Data validation included both plausibility checks within the primary data and consistency checks of information given in primary and secondary data. CONCLUSION: The linkage of primary and secondary data on the individual level offers great opportunities for using the strengths of different data sources synergistically and overcoming some of their limitations. Statutory health insurance data and medical data from kindergarten- and school-entry-examinations of Saxon health authorities are examples of already existing data sources that can complement cost-consuming primary data collections by valuable data sets and open up opportunities for longitudinal analysis.

Impact of birthweight on health-care utilization during early childhood - a birth cohort study.

BACKGROUND: Comprehensive data are needed to evaluate the burden of low birthweight. Analysis of routine data on health-care utilization during early childhood were used to test the hypothesis that infants with low birthweight have (i) increased inpatient health-care utilization, (ii) higher hospital costs and (iii) different morbidity pattern in early childhood when compared with normal birthweight infants. METHODS: Children born between 2007 and 2013 that were insured at birth with the statutory health insurance AOK PLUS were included (N = 118,166, equaling 49% of the Saxon newborns) and classified into very low (< 1500 g, VLBW), low (1500-2499 g, LBW) birthweight and reference group (> 2500 g). Outcomes were: inpatient health-care utilization quantified by number and length of hospital stays; costs of hospitalizations including medication; reasons of hospitalizations for each year of life (YOL). RESULTS: 72, 38 and 22% of VLBW-, LBW- and reference group were hospitalized after perinatal period within the first YOL with a more than 5-fold increased risk in VLBW to be hospitalized for hemangioma, convulsions, hydrocephalus, hernia and respiratory problems. Median (IQR) cumulative cost of inpatient care during the first four YOLs was 2953 (1213-7885), 1331 (0-3451) and 0 (0-2062) Euro for respective groups. Inpatient early childhood health-care utilization (after first YOL) was higher in VLBW compared to healthy, normal birth weight infants (RR 3.92 [95%-CI 3.63, 4.23]), residents of rural areas (RR 1.37 [95%-CI 1.35, 1.40]) and in boys (RR 1.31 [95%-CI 1.29, 1.33]). CONCLUSION: This large population-based birth-cohort study indicates a high clinical and economic burden of low birthweight which is not restricted to the first year of life.

Deep-sea mining: Interdisciplinary research on potential environmental, legal, economic, and societal implications.

Deep-sea mining refers to the retrieval of marine mineral resources such as Mn nodules, FeMn crusts, and seafloor massive sulfide deposits, which contain a variety of metals that serve as crucial raw materials for a range of applications, from electronic devices to renewable energy technologies to construction materials. With the intent of decreasing dependence on imports, supporting the economy, and potentially even overcoming the environmental problems related to conventional terrestrial mining, a number of public and private institutions have rediscovered their interest in exploring the prospects of deep-sea mining, which had been deemed economically and technically unfeasible in the early 1980s. To date, many national and international research projects are grappling to understand the economic environmental, social, and legal implications of potential commercial deep-sea mining operations: a challenging endeavor due to the complexity of direct impacts and spillover effects. In this paper, we present a comprehensive overview of the current state of knowledge in the aforementioned fields as well as a comparison of the impacts associated with conventional terrestrial mining. Furthermore, we identify knowledge gaps that should be urgently addressed to ensure that the world at large benefits from safe, efficient, and environmentally sound mining procedures. We conclude by highlighting the need for interdisciplinary research and international cooperation. Integr Environ Assess Manag 2018;14:672-691. © 2018 SETAC.

Fishing in acid waters: A vulnerability assessment of the Norwegian fishing industry in the face of increasing ocean acidification.

Ocean acidification (OA) describes a change in the ocean's carbonate chemistry. Whereas its chemical processes are largely understood, the biological and socioeconomic consequences particularly in relation to fisheries are less known. Norway is a major fishing nation worldwide and is potentially affected by OA. To improve the understanding of the socioeconomic consequences of OA, we conducted a risk assessment among the Norwegian counties using a modified version of a risk assessment framework introduced in the Intergovernmental Panel on Climate Change's "Special Report: Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation," which considers risk to be the sum of hazard, exposure, and vulnerability. Our results show that about 13 of 19 counties are likely to experience moderate to high risk from OA. We highlight that the success of integrated risk assessments highly depends on the availability of detailed environmental, economic, and societal data. In the case of Norway, modeling data regarding the progress of OA, improved information on potential biological impacts on a larger number of species, and statistical data on social variables are required. We conclude that although still in its infancy, integrated risk assessments are important prerequisites for any form of interdisciplinary research on OA and the development of successful response strategies. Integr Environ Assess Manag 2017;13:778-789. ©2016 SETAC.

Effects of Volatile Anesthetics on Mortality and Postoperative Pulmonary and Other Complications in Patients Undergoing Surgery: A Systematic Review and Meta-analysis.

BACKGROUND: It is not known whether modern volatile anesthetics are associated with less mortality and postoperative pulmonary or other complications in patients undergoing general anesthesia for surgery. METHODS: A systematic literature review was conducted for randomized controlled trials fulfilling following criteria: (1) population: adult patients undergoing general anesthesia for surgery; (2) intervention: patients receiving sevoflurane, desflurane, or isoflurane; (3) comparison: volatile anesthetics versus total IV anesthesia or volatile anesthetics; (4) reporting on: (a) mortality (primary outcome) and (b) postoperative pulmonary or other complications; (5) study design: randomized controlled trials. The authors pooled treatment effects following Peto odds ratio (OR) meta-analysis and network meta-analysis methods. RESULTS: Sixty-eight randomized controlled trials with 7,104 patients were retained for analysis. In cardiac surgery, volatile anesthetics were associated with reduced mortality (OR = 0.55; 95% CI, 0.35 to 0.85; P = 0.007), less pulmonary (OR = 0.71; 95% CI, 0.52 to 0.98; P = 0.038), and other complications (OR = 0.74; 95% CI, 0.58 to 0.95; P = 0.020). In noncardiac surgery, volatile anesthetics were not associated with reduced mortality (OR = 1.31; 95% CI, 0.83 to 2.05, P = 0.242) or lower incidences of pulmonary (OR = 0.67; 95% CI, 0.42 to 1.05; P = 0.081) and other complications (OR = 0.70; 95% CI, 0.46 to 1.05; P = 0.092). CONCLUSIONS: In cardiac, but not in noncardiac, surgery, when compared to total IV anesthesia, general anesthesia with volatile anesthetics was associated with major benefits in outcome, including reduced mortality, as well as lower incidence of pulmonary and other complications. Further studies are warranted to address the impact of volatile anesthetics on outcome in noncardiac surgery.

Psoriasis and cardiometabolic traits: modest association but distinct genetic architectures.

Psoriasis has been linked to cardiometabolic diseases, but epidemiological findings are inconsistent. We investigated the association between psoriasis and cardiometabolic outcomes in a German cross-sectional study (n=4,185) and a prospective cohort of German Health Insurance beneficiaries (n=1,811,098). A potential genetic overlap was explored using genome-wide data from >22,000 coronary artery disease and >4,000 psoriasis cases, and with a dense genotyping study of cardiometabolic risk loci on 927 psoriasis cases and 3,717 controls. After controlling for major confounders, in the cross-sectional analysis psoriasis was significantly associated with type 2 diabetes (T2D, adjusted odds ratio (OR)=2.36; 95% confidence interval CI=1.26-4.41) and myocardial infarction (MI, OR=2.26; 95% CI=1.03-4.96). In the longitudinal study, psoriasis slightly increased the risk for incident T2D (adjusted relative risk (RR)=1.11; 95% CI=1.08-1.14) and MI (RR=1.14; 95% CI=1.06-1.22), with highest risk increments in systemically treated psoriasis, which accounted for 11 and 17 excess cases of T2D and MI per 10,000 person-years. Except for weak signals from within the major histocompatibility complex, there was no evidence of genetic risk loci shared between psoriasis and cardiometabolic traits. Our findings suggest that psoriasis, in particular severe psoriasis, increases the risk for T2D and MI, and that the genetic architecture of psoriasis and cardiometabolic traits is largely distinct.