Southern Ocean drives multidecadal atmospheric CO2 rise during Heinrich Stadials.

The last glacial period was punctuated by cold intervals in the North Atlantic region that culminated in extensive iceberg discharge events. These cold intervals, known as Heinrich Stadials, are associated with abrupt climate shifts worldwide. Here, we present CO2 measurements from the West Antarctic Ice Sheet Divide ice core across Heinrich Stadials 2 to 5 at decadal-scale resolution. Our results reveal multi-decadal-scale jumps in atmospheric CO2 concentrations within each Heinrich Stadial. The largest magnitude of change (14.0 ± 0.8 ppm within 55 ± 10 y) occurred during Heinrich Stadial 4. Abrupt rises in atmospheric CO2 are concurrent with jumps in atmospheric CH4 and abrupt changes in the water isotopologs in multiple Antarctic ice cores, the latter of which suggest rapid warming of both Antarctica and Southern Ocean vapor source regions. The synchroneity of these rapid shifts points to wind-driven upwelling of relatively warm, carbon-rich waters in the Southern Ocean, likely linked to a poleward intensification of the Southern Hemisphere westerly winds. Using an isotope-enabled atmospheric circulation model, we show that observed changes in Antarctic water isotopologs can be explained by abrupt and widespread Southern Ocean warming. Our work presents evidence for a multi-decadal- to century-scale response of the Southern Ocean to changes in atmospheric circulation, demonstrating the potential for dynamic changes in Southern Ocean biogeochemistry and circulation on human timescales. Furthermore, it suggests that anthropogenic CO2 uptake in the Southern Ocean may weaken with poleward strengthening westerlies today and into the future.

Quantifying the benefits of early sublingual allergen immunotherapy tablet initiation in children.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the upper airway, which progresses into allergic asthma (AA) in up to 45% of children. This analysis aimed to investigate clinical and economic benefits of sublingual allergen immunotherapy (SLIT tablets) initiated early in childhood for the treatment of AR by quantifying the long-term reduction in new cases of AA. METHODS: A Markov model was developed to estimate the long-term effects of SLIT tablets on the risk of developing asthma. Key parameters were primarily based on data from the GRAZAX® Asthma Prevention trial and included the age- and treatment-dependent risk of developing AA as well as annual probabilities of progression/remission in AR severity. Healthcare costs were estimated using data from the REACT study. RESULTS: In a modelled cohort of children with moderate-to-severe seasonal AR initiated on SLIT tablets at ages 7 and 12, 24% and 29%, respectively, develop AA during a 20-year period. In comparison, when initiated at age 5, 19% develop AA. Additionally, initiation of SLIT tablets at age 5 is associated with a total healthcare cost of EUR 20,429 per patient, whereas initiation at ages 7 and 12 is associated with, respectively, EUR 21,050 and EUR 22,379 per patient 20 years after AR diagnosis. CONCLUSION: Initiation of SLIT tablets in early childhood is associated with a clinically meaningful and permanent reduction in new cases of AA and lower healthcare costs among children with AR. This finding supports the clinical relevance of initiating SLIT tablets early for children with AR to obtain long-term clinical benefits.

Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis.

BACKGROUND: Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures. OBJECTIVES: To compare binary efficacy outcomes of systemic treatments for AD. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes included the proportion of patients achieving at least 50%, 75% and 90% improvements in Eczema Area and Severity Index (EASI 50, EASI 75 and EASI 90, respectively) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian NMAs to calculate odds ratios (OR) and 95% credible intervals (CrIs) between each intervention for each outcome. RESULTS: Eighty-three trials with 22 122 participants were included in the systematic review. In analyses limited to trials of 8-16 weeks' duration with predominantly adult populations, abrocitinib 200 mg daily (OR 1.5, 95% CrI 1.1-2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9-3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3-5.0) were associated with higher odds of achieving EASI 50 vs. dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5-1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3-0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3-0.7), and tralokinumab (OR 0.4, 95% CrI 0.3-0.6) were associated with lower odds of achieving EASI 50 vs. dupilumab. Results were similar for EASI 75, EASI 90 and IGA success. CONCLUSIONS: Supporting results for continuous outcome measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regard to binary efficacy endpoints up to 16 weeks in adults with moderate-to-severe AD, followed by upadacitinib 15 mg daily, dupilumab and abrocitinib 100 mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2 mg daily and tralokinumab.

Epidemiology and risk factors of community-acquired pneumonia in patients with different causes of immunosuppression.

Immunosuppression constitutes a significant risk for community-acquired pneumonia (CAP). Nevertheless, specific causes of immunosuppression and their relevance for incidence, etiology and prognosis of CAP are insufficiently investigated.We conducted a population-based cohort study within a statutory health insurance in Germany from 2015 to 2018. CAP was retrieved by ICD-10-GM codes. Episodes of immunosuppression were identified by coded conditions (hematologic neoplasms, stem cell or organ transplantation, neutropenia, HIV, primary immunosuppressive syndromes) or treatments (immunosuppressants, antineoplastic drugs, systemic steroids). Endpoints were defined as occurrence of CAP (primary), hospitalization, 30-day mortality and CAP associated with rare pathogens. Our analysis utilized the Andersen-Gill model adjusted for sex, age, level of long-term care, vaccination status, community type and comorbidities.942,008 individuals with 54,781 CAPs were included (hospitalization 55%, 30-day mortality 14.5%). 6% of individuals showed at least one episode of immunosuppression during the study period with systemic steroids (39.8%) and hematologic neoplasms (26.7%) being most common. Immunosuppression was recorded in 7.7% of CAPs. Besides classical risk factors such as age and level of long-term care, immunosuppressed patients were most prone to CAP (HR 2.4[2.3-2.5]) and consecutive death (HR 1.9[1.8-2.1]). Organ and stem cell transplantation (HR 3.2[2.6-4.0] and 2.8[2.1-3.7], respectively), HIV (HR 3.2[1.9-5.4]) and systemic steroids (> 20 mg prednisone daily dose equivalent (HR 2.7[2.4-3.1])) showed the highest risk for contracting CAP. CAP by rare pathogens was strongly associated with immunosuppression (HR 17.1[12.0-24.5]), especially HIV (HR 34.1[7.6-153]) and systemic steroids (HR 8.2[4.6-14.8]).Our study elucidates the relevance of particular immunosuppressive conditions including systemic steroids for occurrence and prognosis of CAP.

Long/post-COVID in children and adolescents: symptom onset and recovery after one year based on healthcare records in Germany.

PURPOSE: Evidence on the incidence and persistence of post-acute sequelae of COVID-19 (PASC) among children and adolescents is still limited. METHODS: In this retrospective cohort study, 59,339 children and adolescents with laboratory-confirmed COVID-19 in 2020 and 170,940 matched controls were followed until 2021-09-30 using German routine healthcare data. Incidence rate differences (ΔIR) and ratios (IRR) of 96 potential PASC were estimated using Poisson regression. Analyses were stratified according to age (0-11, 12-17 years), and sex. At the individual level, persistence of diagnoses in patients with onset symptoms was tracked starting from the first quarter post-infection. RESULTS: At 0-3 month follow-up, children and adolescents with a previous SARS-CoV-2 infection showed a 34% increased risk of adverse health outcome, and approximately 6% suffered from PASC in association with COVID-19. The attributable risk was higher among adolescents (≥ 12 years) than among children. For most common symptoms, IRRs largely persisted at 9-12 month follow-up. IRR were highest for rare conditions strongly associated with COVID-19, particularly inflammatory conditions among children 0-11 years, and chronic fatigue and respiratory insufficiency among adolescents. Tracking of diagnoses at the individual level revealed similar rates in the decline of symptoms among COVID-19 and control cohorts, generally leaving less than 10% of the patients with persistent diagnoses after 12 months. CONCLUSION: Although very few patients presented symptoms for longer than 12 months, excess morbidity among children and, particularly, adolescents with a history of COVID-19 means a relevant burden for pediatric care.

Changes in patient care through flexible and integrated treatment programs in German psychiatric hospitals: meta-analyses based on a series of controlled claims-based cohort studies.

BACKGROUND: Global treatment budgets, i.e. predefined budgets for patients treated in hospital independent of the setting within the hospital, together with flexible and integrated treatment (FIT) have been introduced in some German psychiatric hospitals since 2013. We investigated pooled changes in inpatient, day-care, outpatient treatment, and continuity of care for patients with mental disorders in 12 FIT-hospitals. METHODS: We conducted a series of 12 controlled cohort studies regarding FIT hospitals using anonymized patient claims data from more than 70 German statutory health insurance funds. Each study compared one FIT-hospital to matched patients from equivalent non-FIT-hospitals (routine care). We included only those patients without treatment in the respective hospital within two years prior to first hospital treatment (either FIT or routine care). We contrasted results between the year prior to with the first and second year after patient's first treatment (treatment continuity: only group comparison) using multivariate multi-level models. To approximate the difference-in-difference effect in the meta-analysis, we used the interaction terms group (FIT hospital vs. routine care) x time (year before vs. first or second patient year after study inclusion) in the Poisson models. RESULTS: The 12 studies included 36,069 patients with 2,358 patients from a Department of child and adolescent psychiatry. The pooled effect revealed a 5.1 days lower increase in inpatient treatment in FIT-hospitals during the first patient year compared to routine care. Results were statistically significant for adult care FIT-hospitals but not for child and adolescent FIT-hospitals. Utilization of day-care treatment increased more in most FIT-hospitals during the first year, while outpatient contacts increased in some and decreased in others. The odds of treatment continuity increased by 1.4 in FIT-hospitals compared to non-FIT-hospitals. CONCLUSIONS: Global treatment budgets lead to the intended changes in mental health care in the majority of FIT-hospitals compared to routine care in this large real-world evidence study from Germany. For child and adolescent psychiatry, more evidence is needed to draw firm conclusions. TRIAL REGISTRATION: This study was registered in the database "Health Services Research Germany" (trial number: VVfD_EVA64_15_003713).

Stratum corneum and microbial biomarkers precede and characterize childhood atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is the most common paediatric inflammatory skin disease. There are currently no robust biomarkers that could reliably predict its manifestation, and on the molecular level, it is less well characterized than adult AD. OBJECTIVES: This study aimed to extend previous findings and provide evidence for distinct changes of the epidermal proteome and microbiome preceding the onset of AD as well as characterizing early AD. METHODS: We longitudinally analysed epidermal biomarker levels and microbial profiles in a cohort of 50 neonates at high risk for AD, who had participated in a randomized controlled trial on early emollient use for AD prevention. RESULTS: About 26% of the infants developed AD until month 24 with an average age of 10 month at disease onset. In children with later AD, IL-1Ra, TNFß, IL-8, IL-18, IL-22, CCL2, TARC, TSLP and VEGFa showed increased levels prior to disease manifestation with levels of IL-1Ra, TNFß and VEGFa already increased shortly after birth. Further, children with later AD displayed a delayed maturation and differentially composed skin microbiome prior to AD onset. At manifestation, levels of multiple Th2, Th17/22 and Th1-associated biomarkers as well as innate immunity markers were elevated, and abundances of commensal Streptococcus species were reduced in favour of Staphylococcus epidermidis. CONCLUSIONS: Our results indicate that elevations of proinflammatory stratum corneum biomarkers and alterations of the skin microbiome precede paediatric AD and characterize the disease at onset.

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.

Evaluation of the telemedical health care network "SAFE BIRTH" for pregnant women at risk, premature and sick newborns and their families: study protocol of a cluster-randomized controlled stepped-wedge trial.

BACKGROUND: The Perinatal Center of the University Hospital Carl Gustav Carus Dresden has initiated the telemedical healthcare network "SAFE BIRTH" to coordinate and improve specialized care in non-metropolitan regions for pregnant women and newborns. The network incorporates five intervention bundles (IB): (1) Multi-professional, inter-disciplinary prenatal care plan; (2) Neonatal resuscitation; (3) Neonatal antibiotic stewardship; (4) Inter-facility transfer of premature and sick newborns; (5) Psycho-social support for parents. We evaluate if the network improves care close to home for pregnant women, premature and sick newborns. METHODS: To evaluate the complex healthcare intervention "SAFE BIRTH" we will conduct a cluster-randomized controlled stepped-wedge trial in five prenatal medical outpatient offices and eight non-metropolitan hospitals in Saxony, Germany. The offices and hospitals will be randomly allocated to five respectively eight sequential steps over a 30-month period to implement the telemedical IB. We define one specific primary process outcome for each IB (for instance IB#1: "Proportion of patients with inclusion criterion IB#1 who have a prenatal care plan and psychosocial counseling within one week"). We estimated a separate multilevel logistic regression model for each primary process outcome using the intervention status as a regressor (control or intervention group). Across all IB, a total of 1,541 and 1,417 pregnant women or newborns need to be included in the intervention and control group, respectively, for a power above 80% for small to medium intervention effects for all five hypothesis tests. Additionally, we will assess job satisfaction and sense of safety of health professionals caring for newborns (questionnaire survey) and we will assess families' satisfaction, resilience, quality of life and depressive, anxiety and stress symptoms (questionnaire surveys). We will also evaluate the cost-effectiveness of "SAFE BIRTH" (statutory health insurance routine data, process data) and barriers to its implementation (semi-structured interviews). We use multilevel regression models adjusting for relevant confounders (e.g. socioeconomic status, age, place of residence), as well as descriptive analyses and qualitative content analyses. DISCUSSION: If the telemedical healthcare network "SAFE BIRTH" proves to be effective and cost-efficient, strategies for its translation into routine care should be developed. TRIAL REGISTRATION: German clinical trials register. DRKS-ID: DRKS00031482.

Treatment in certified cancer centers is related to better survival in patients with colon and rectal cancer: evidence from a large German cohort study.

BACKGROUND: Certified cancer centers aim to ensure high-quality care by establishing structural and procedural standards according to evidence-based guidelines. Despite the high clinical and health policy relevance, evidence from a nation-wide study for the effectiveness of care for colorectal cancer in certified centers vs. other hospitals in Germany is still missing. METHODS: In a retrospective cohort study covering the years 2009-2017, we analyzed patient data using demographic information, diagnoses, and treatments from a nationwide statutory health insurance enriched with information on certification. We investigated whether patients with incident colon or rectal cancer did benefit from primary therapy in a certified cancer center. We used relative survival analysis taking into account mortality data of the German population and adjustment for patient and hospital characteristics via Cox regression with shared frailty for patients in hospitals with and without certification. RESULTS: The cohorts for colon and rectal cancer consisted of 109,518 and 51,417 patients, respectively, treated in a total of 1052 hospitals. 37.2% of patients with colon and 42.9% of patients with rectal cancer were treated in a certified center. Patient age, sex, comorbidities, secondary malignoma, and distant metastases were similar across groups (certified/non-certified) for both colon and rectal cancer. Relative survival analysis showed significantly better survival of patients treated in a certified center, with 68.3% (non-certified hospitals 65.8%) 5-year survival for treatment of colon cancer in certified (p < 0.001) and 65.0% (58.8%) 5-year survival in case of rectal cancer (p < 0.001), respectively. Cox regression with adjustment for relevant covariates yielded a lower hazard of death for patients treated in certified centers for both colon (HR = 0.92, 95% CI = 0.89-0.95) and rectal cancer (HR = 0.92, 95% CI = 0.88-0.95). The results remained robust in a series of sensitivity analyses. CONCLUSIONS: This large cohort study yields new important evidence that patients with colorectal cancer have a better chance of survival if treated in a certified cancer center. Certification thus provides one powerful means to improve the quality of care for colorectal cancer. To decrease the burden of disease, more patients should thus receive cancer care in a certified center.

Shifting from Theoretical Best Evidence to Practical Best Evidence: an Approach to Overcome Structural Conservatism of Evidence-Based Medicine and Health Policy. / Von der theoretisch besten Evidenz zur praktisch besten Evidenz: ein Ansatz zur Überwindung des Strukturkonservatismus in der evidenzbasierten Medizin und Gesundheitspolitik.

There is disparity in the healthcare sector between the extent of innovation in medical products (e. g., drugs) and healthcare structures. The reason is not a lack of ideas, concepts, or (quasi-) experimental studies on structural innovations. Instead, we argue that the slow implementation of structural innovations has created this disparity partly because evidence-based medicine (EBM) instruments are well suited to evaluate product innovations but less suited to evaluate structural innovations. This article argues that the unintentional interplay between EBM, which has changed significantly over time to become primarily theoretical, on the one hand, and caution and inertia in health policy, on the other, has resulted in structural conservatism. Structural conservatism is present when healthcare structures persistently and essentially resist innovation. We interpret this phenomenon as an unintended consequence of deliberate EBM action. Therefore, we propose a new assessment framework to respond to structural innovations in healthcare, centered on the differentiation between the theoretical best (possible) evidence, the practical best (possible) evidence, and the best available evidence.

[An Experience Report on the Evaluation of New Forms of Care for People with Mental Illness: Pros and Cons of the Use of SHI Claims Data]. / Evaluation von neuen Versorgungsformen für Menschen mit psychischen Erkrankungen: Pro & Contra zum Einsatz von GKV-Routinedaten ­ Ein Erfahrungsbericht.

The present article describes the special features of an evaluation of research in mental health services in Germany. The experiences of the evaluation of flexible and integrated treatment options with a global treatment budget in psychiatric hospitals based on routine data of more than 70 statutory health insurance (SHI) funds (EVA64 study) are systematically presented. Using the EVA64 study as an example, recommendations for the use of claims data in the field of mental health services research and in general are derived. (1) First, the study and its use of claims data is described and classified. (2) The individual outcomes of the study are presented and evaluated in order to (3) derive criteria, identify strengths and suggest potential uses of claims data. (4) Finally, recommendations for the further development of claims data from SHI funds as a basis for evaluation are described.

[Patient safety in the Innovation Fund - Characterization, results and evaluation of completed projects: Results of a scoping review]. / Patientensicherheit im Innovationsfonds ­ Charakterisierung, Resultate und Bewertung abgeschlossener Projekte: Ergebnisse eines Scoping Reviews.

The German Innovation Fund has funded various studies on patient safety. Their thematic spectrum, methodological quality, results and recommendations of the Innovation committee were to be systematically investigated in order to derive proposals for optimizing transfer success. As part of a scoping review, all Innovation Fund projects funded in the period 2016-02/2023 with a focus on patient safety were analyzed. Each included study document was critically reviewed by two independent persons. The 16 included projects addressed a wide range of populations, indications and interventions. The study quality was mostly good. The results ranged from feasible indicator sets and the prevention of adverse drug reactions to the optimization of error management. For seven projects, the Innovation Committee recommended forwarding the results to healthcare institutions with the request that they take note and/or examine the feasibility of implementation in standard care. Implementation, however, has not yet taken place. In order to facilitate implementation, the joint development of an implementation strategy by the recipients of the Innovation Committee's recommendations is necessary.

[Does the Innovation Fund Improve Healthcare Provision? A Critical Assessment of the Status of Implementing Successful Innovation Fund Projects into Healthcare Practice]. / Verbessert der Innovationsfonds die Versorgung? Eine kritische Bestandsaufnahme zum Stand der Implementierung erfolgreicher Innovationsfondsprojekte in die Versorgungspraxis.

INTRODUCTION: Since 2015, the Federal Joint Committee (G-BA)'s Innovation Fund has been supporting projects in health services research and new health service models ("Neue Versorgungsformen", NVF). By the end of 2022, 211 projects in the NVF category had been funded. A key objective is the transfer of successful projects into standard care. This article analyzes previous projects regarding their incorporation into routine care based on transfer recommendations of the Innovation Fund Committee ("Innovationsausschuss" IA). METHOD: Descriptive analysis of all projects completed by August 1, 2023 with transfer recommendations in the "NVF" funding stream. Presentation by topic, project duration, time until IA transfer decision, categorization, and number of institutions and organizations (recipients) addressed per project, their feedback published on the G-BA website, response rates per recipient group, and a content classification and interpretation of exemplary feedback. Recommendations based on the results and their discussion in an expert workshop. RESULTS: Out of 57 NVF projects, 17 had a transfer recommendation. A total of 57 feedback responses were received from a total of 431 recipients addressed by the IA across these projects. Response rates varied significantly. One-third of inquiries to the G-BA and its member organizations received a response (31%), while only every fifth inquiry to federal states (18%) and professional societies (18%) got a response. Less than one in ten inquiries to the Federal Ministry of Health (8%), administrative bodies (6%), and the German Medical Association (0%) received a response. Project-specific feedback within a recipient group was often contradictory or limited to regional scope. DISCUSSION AND CONCLUSION: The transfer process reveals significant structural and procedural obstacles regarding the incorporation of projects evaluated as successful into routine health care. To ensure that funding from the innovation fund is most effectively used, there needs to be a realistic chance of successful transfer of positive project outcomes into routine care. The DNVF recommends stronger involvement of rule-competent institutions, mandatory publication of responses, structured moderation of the transfer process, expanding types of selective contracts, financing of implementation phases and of studies drawing on results across successful NVF projects.

S3 Guideline Atopic dermatitis: Part 1 - General aspects, topical and non-drug therapies, special patient groups.

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD.

S3 guideline Atopic dermatitis: Part 2 - Systemic treatment.

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups.

[Perinatal Networks: Ensuring Regional Care of Pregnant Woman and Newborns]. / Perinatologische Kompetenznetzwerke: Die Versorgung von Schwangeren und Neugeborenen in einer Region.

Health care of pregnant women and their newborns is facing major challenges due to the decline in birth rate and shortage of specialists. In the current discussion about future concepts, the centralization associated with minimum quantities and the necessary safeguarding of care in the area are often construed as conflicting goals. Instead, concepts are needed to guarantee that pregnant women and their children will continue to receive care close to home. The example of the saxony center for feto/neonatal health is used to show how partners in a region can jointly ensure care during pregnancy, birth and the neonatal period on a supra-local and cross-hospital basis. The close cooperation of maximum care providers with regional partners enables comprehensive health care. At the same time, this cooperation enables hospitals to remain attractive employers in structurally weak regions and to provide comprehensive care for young families in need of medical services related to pregnancy and birth through good family and social integration close to home and work. The overriding goals of the saxony center for feto/neonatal health are optimal, guideline-based, interdisciplinary and intersectoral care of pregnant women and premature or sick newborns in the region.

Allergic diseases as risk factors for Long-COVID symptoms: Systematic review of prospective cohort studies.

OBJECTIVE: The role of allergy as a risk factor for Long-COVID (LC) is unclear and has not been thoroughly examined yet. We aimed to systematically review and appraise the epidemiological evidence on allergic diseases as risk factors for LC. DESIGN: This is an initial systematic review. Two reviewers independently performed the study selection and data extraction using Covidence. Risk of bias (RoB) and certainty of evidence (GRADE) were assessed. Random effects meta-analyses were used to pool unadjusted ORs within homogeneous data subsets. DATA SOURCES: We retrieved articles published between January 1st, 2020 and January 19th, 2023 from MEDLINE via PubMed, Scopus, the WHO-COVID-19 database and the LOVE platform (Epistemonikos Foundation). In addition, citations and reference lists were searched. ELIGIBILITY CRITERIA: We included prospective cohort studies recruiting individuals of all ages with confirmed SARS-CoV-2 infection that were followed up for at least 12 months for LC symptoms where information on pre-existing allergic diseases was available. We excluded all study designs that were not prospective cohort studies and all publication types that were not original articles. RESULTS: We identified 13 studies (9967 participants, range 39-1950 per study), all assessed as high RoB, due to population selection and methods used to ascertain the exposures and the outcome. Four studies did not provide sufficient data to calculate Odds Ratios. The evidence supported a possible relationship between LC and allergy, but was very uncertain. For example, pre-existing asthma measured in hospital-based populations (6 studies, 4019 participants) may be associated with increased risk of LC (Odds Ratio 1.94, 95% CI 1.08, 3.50) and findings were similar for pre-existing rhinitis (3 studies, 1141 participants; Odds Ratio 1.96, 95% CI 1.61, 2.39), both very low certainty evidence. CONCLUSIONS: Pre-existing asthma or rhinitis may increase the risk of LC.

Adherence and persistence in allergen immunotherapy (APAIT): A reporting checklist for retrospective studies.

BACKGROUND: Adherence is essential for the long-term efficacy of allergen immunotherapy (AIT) and has been evaluated in numerous retrospective studies. However, there are no published guidelines for best practice in measuring and reporting adherence or persistence to AIT, which has resulted in substantial heterogeneity among existing studies. The 'adherence and persistence in AIT (APAIT)' checklist has been developed to guide the reporting, design and interpretation of retrospective studies that evaluate adherence or persistence to AIT in clinical practice. METHODS: Five existing checklists, focussing on study protocol design, the use of retrospective databases/patient registries, and the appraisal and reporting of observational studies, were identified and merged. Relevant items were selected and tailored to be specific to AIT. The content of the checklist was discussed by 11 experts from Europe, the United States and Canada, representing allergy, healthcare and life sciences, and health technology appraisal. RESULTS: The APAIT checklist presents a set of items that should either be included or at least considered, when reporting retrospective studies that assess adherence or persistence to AIT. Items are organized into four categories comprising study objective, design and methods, data analysis, and results and discussion. The checklist highlights the need for clarity and transparency in reporting and emphasizes the importance of considering potential sources of bias in retrospective studies evaluating adherence or persistence to AIT. CONCLUSIONS: The APAIT checklist provides a pragmatic guide for reporting retrospective adherence and persistence studies in AIT. Importantly, it identifies potential sources of bias and discusses how these influence outcomes.

Dupilumab but not cyclosporine treatment shifts the microbiome toward a healthy skin flora in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) patients display an altered skin microbiome which may not only be an indicator but also a driver of inflammation. We aimed to investigate associations among AD patients' skin microbiome, clinical data, and response to systemic therapy in patients of the TREATgermany registry. METHODS: Skin swabs of 157 patients were profiled with 16S rRNA gene amplicon sequencing before and after 3 months of treatment with dupilumab or cyclosporine. For comparison, 16s microbiome data from 258 population-based healthy controls were used. Disease severity was assessed using established instruments such as the Eczema Area and Severity Index (EASI). RESULTS: We confirmed the previously shown correlation of Staphylococcus aureus abundance and bacterial alpha diversity with AD severity as measured by EASI. Therapy with Dupilumab shifted the bacterial community toward the pattern seen in healthy controls. The relative abundance of Staphylococci and in particular S. aureus significantly decreased on both lesional and non-lesional skin, whereas the abundance of Staphylococcus hominis increased. These changes were largely independent from the degree of clinical improvement and were not observed for cyclosporine. CONCLUSIONS: Systemic treatment with dupilumab but not cyclosporine tends to restore a healthy skin microbiome largely independent of the clinical response indicating potential effects of IL-4RA blockade on the microbiome.