State-of-the-art diagnosis of autoimmune blistering diseases.

Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin ß4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.

Medication Risks and Their Association with Patient-Reported Outcomes in Inpatients with Cancer.

BACKGROUND: We aimed to assess medication risks and determine factors influencing the health-related quality of life (HRQOL) in cancer inpatients. METHODS: A retrospective analysis was conducted to identify drug-related problems (DRPs) based on medication reviews, including patient-reported outcomes (PROs). Multiple linear regression analyses were performed to identify sociodemographic, disease-related, and drug therapy-related factors influencing changes from hospital admission to discharge in the scales of the EORTC QLQ-C30 questionnaire. RESULTS: A total of 162 inpatients with various hematological and solid cancer diseases was analyzed. Patients received a mean of 11.6 drugs and 92.6% of patients exhibited polymedication resulting in a mean of 4.0 DRPs per patient. Based on PRO data, 21.5% of DRPs were identified. Multiple linear regression models described the variance of the changes in global HRQOL and physical function in a weak-to-moderate way. While drug therapy-related factors had no influence, relapse status and duration of hospital stay were identified as significant covariates for global HRQOL and physical function, respectively. CONCLUSION: This analysis describes underlying DRPs in a German cancer inpatient population. PROs provided valuable information for performing medication reviews. The multiple linear regression models for global HRQOL and physical function provided explanations for changes during hospital stay.

Acute cardiovascular and muscular response to rowing ergometer exercise in artificial gravity - a pilot trial.

Prolonged immobilization and spaceflight cause cardiovascular and musculoskeletal deconditioning. Combining artificial gravity through short-arm centrifugation with rowing exercise may serve as a countermeasure. We aimed to compare the tolerability, muscle force production, cardiovascular response, and power output of rowing on a short-arm centrifuge and under terrestrial gravity. Twelve rowing athletes (4 women, aged 27.2 ± 7.4 years, height 179 ± 0.1 cm, mass 73.7 ± 9.4 kg) participated in two rowing sessions, spaced at least six weeks apart. One session used a short-arm centrifuge with +0.5 Gz, while the other inclined the rowing ergometer by 26.6° to mimic centrifugal loading. Participants started self-paced rowing at 30 W, increasing by 15 W every three minutes until exhaustion. We measured rowing performance, heart rate, blood pressure, ground reaction forces, leg muscle activation, and blood lactate concentration. Rowing on the centrifuge was well-tolerated without adverse events. No significant differences in heart rate, blood pressure, or blood lactate concentration were observed between conditions. Inclined rowing under artificial gravity resulted in lower power output (-33%, p < 0.001) compared to natural gravity, but produced higher mean and peak ground reaction forces (p < 0.0001) and increased leg muscle activation. Muscle activation and ground reaction forces varied with rotational direction. Rowing in artificial gravity shows promise as a strategy against cardiovascular and muscular deconditioning during long-term spaceflight, but further investigation is required to understand its long-term effects.

Urban-rural inequalities in IV thrombolysis for acute ischemic stroke: A nationwide study.

INTRODUCTION: Rural residency has been associated with lower reperfusion treatment rates for acute ischemic stroke in many countries. We aimed to explore urban-rural differences in IV thrombolysis rates in a small country with universal health care, and short transport times to stroke units. PATIENTS AND METHODS: In this nationwide cohort study, adult ischemic stroke patients registered in the Danish Stroke Registry (DSR) between 2015 and 2020 were included. The exposure was defined by residence rurality. Data from the DSR, Statistics Denmark, and the Danish Health Data Authority, were linked on the individual level using the Civil Registration Number. Adjusted treatment rates were calculated by balancing baseline characteristics using inverse probability of treatment weights. RESULTS: Among the included 56,175 patients, prehospital delays were shortest for patients residing in capital municipalities (median 4.7 h), and longest for large town residents (median 7.1 h). Large town residents were predominantly admitted directly to a comprehensive stroke center (98.5%), whereas 30.9% of capital residents were admitted to a hospital with no reperfusion therapy available (non-RT unit). Treatment rates were similar among all non-rural residents (18.5%-18.7%), but slightly lower among rural residents (17.2% [95% CI 16.5-17.8]). After adjusting for age, sex, immigrant status, and educational attainment, rural residents reached treatment rates comparable to capital and large town residents at 18.5% (95% CI 17.7-19.4). DISCUSSION AND CONCLUSION: While treatment rates varied minimally by urban-rural residency, substantial differences in median prehospital delay and admission to non-RT units underscored marked urban-rural differences in potential obstacles to reperfusion therapies.

Effectiveness of the online-eLearning program KeepCoool at improving the vaccine cold chain in general practices.

BACKGROUND: Protecting vaccines from freeze damage is a poorly addressed problem. We describe the effectiveness of the eLearning KeepCoool on cold chain maintenance in general practices. METHODS: For this intervention study, temperatures of vaccine refrigerators were logged at one-minute intervals. Personnel from practices with cold chain breaches was offered the eLearning. The primary outcome was the intervention's effectiveness to achieve temperatures in the target range (2 to 8°C) in the sixth week (follow-up) compared to the first (baseline). Using continuous temperature data, a generalized additive model for location, scale and shape was estimated. RESULTS: The practice response rate was 38% (64 of 168). At baseline, 73% of the practices and 68% of the refrigerators (51 of 75) showed cold chain breaches. 47% of the practices (n = 22 with 24 refrigerators) participated in the eLearning (55 physicians and practice assistants). At follow-up, 17% of those refrigerators were in the target range continuously, 38% reached targets 95% of the time while always >0°C, and temperatures ≤0°C decreased by 63%. Based on 2 million temperature data, the average Euclidian distance based on regression showed a significant improvement (p<0.05). CONCLUSION: The eLearning KeepCoool improved the practices´ vaccine cold chain. It is freely available at https://keepcoool.ukbonn.de.

Investigating the spatiotemporal associations between meteorological conditions and air pollution in the federal state Baden-Württemberg (Germany).

When analyzing health data in relation to environmental stressors, it is crucial to identify which variables to include in the statistical model to exclude dependencies among the variables. Four meteorological parameters: temperature, ultraviolet radiation, precipitation, and vapor pressure and four outdoor air pollution parameters: ozone ( O 3 ), nitrogen dioxide ( NO 2 ), particulate matter ( P M 2.5 , P M 10 ) were studied on a daily basis for Baden-Württemberg (Germany). This federal state covers urban and rural compartments including mountainous and river areas. A temporal and spatial analysis of the internal relationships was performed among the variables using (a) cross-correlations, both on the grand ensemble of data as well as within subsets, and (b) the Local Indications of Spatial Association (LISA) method. Meteorological and air pollution variables were strongly correlated within and among themselves in time and space. We found a strong interaction between nitrogen dioxide and ozone, with correlation coefficients varying over time. The coefficients ranged from negative correlations in January (-0.84), April (-0.47), and October (-0.54) to a positive correlation in July (0.45). The cross-correlation plot showed a noticeable change in the correlation direction for O 3 and NO 2 . Spatially, NO 2 , P M 2.5 , and P M 10 concentrations were significantly higher in urban than rural regions. For O 3 , this effect was reversed. A LISA analysis confirmed distinct hot and cold spots of environmental stressors. This work examined and quantified the spatio-temporal relationship between air pollution and meteorological conditions and recommended which variables to prioritize for future health impact analyses. The results found are in line with the underlying physico-chemical atmospheric processes. It also identified postal code areas with dominant environmental stressors for further studies.

Mixed stones: urinary stone composition, frequency and distribution by gender and age.

Proper analysis of urinary stone composition is a cornerstone for diagnosis, targeted treatment and recurrence prevention of urolithiasis. The aim of this study was to determine the composition, frequency and distribution of mixed stones according to gender and age of patients. A total of 42,519 urinary stones from 30,311 men and 12,208 women submitted between January 2007 and December 2020 were studied. Most urinary calculi consisted of two components (50.9%), followed by stones of a single constituent (27.1%) and three-component stones (21.9%), while four-component stones were only rarely identified (0.1%). Among all stones, 49.8% consisted of whewellite (COM), weddellite (COD), and mixtures of COM and COD, 33.8% were pure carbonate apatite (CA) and mixtures of CA with COM and/or COD, while 7.6% were composed of uric acid anhydrous (UAA), uric acid dihydrate (UAD), and mixed UAA and UAD. The remaining 8.8% of calculi were rare single-component stones and rare mixtures of various constituents. The number of stone components was inversely associated with age (p < 0.001). The proportion of men decreased significantly with the number of stone constituents, from 3.01:1 for single-component stones to 1.0:1 for four-component urinary calculi (p < 0.001). The vast majority of urinary calculi consisted of two or more components in varying proportions. While age was inversely associated with the number of stone constituents, the proportion of women increased significantly from single-component to four-component urinary calculi. A significant proportion of mixed stones could present a challenge for diagnosis and targeted recurrence prevention.

Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P=0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes (P=0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes (P=0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03542188.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

[Pemphigoid diseases in older adults]. / Pemphigoiderkrankungen bei älteren Menschen.

Pemphigoid diseases are a group of bullous autoimmune diseases characterized by autoantibodies against structural proteins of the dermal-epidermal junction. With a steadily growing aging population, pemphigoid diseases are emerging as a significant medical challenge, because they occur primarily in older individuals. The by far most common disease is bullous pemphigoid, which is clinically characterized by tense blisters, erosions, erythema or urticarial plaques, while severe pruritus is the leading subjective symptom. Mucous membrane pemphigoid predominantly affects surface-close mucous membranes with painful erosions and blisters as well as frequently scarring usually in the mouth, nose, and eyes. Anti-p200 pemphigoid clinically resembles bullous pemphigoid but is much less common. Diagnosis of these diseases involves the combination of clinical evaluation, lesional histopathology, direct immunofluorescence microscopy of a perilesional biopsy and serology. Topical and systemic corticosteroids are the mainstay of pemphigoid diseases treatment. Depending on the severity of the disease, various potentially corticosteroid-sparing therapies, such as dapsone, doxycycline, methotrexate, azathioprine and mycophenolate may be used. In severe courses, treatment with rituximab, cyclophosphamide, intravenous immunoglobulins or immunoadsorption are second- or third-line treatment options. Patients are best managed in centers experience with the management of pemphigoid diseases. Updated national and international guidelines for the diagnosis and treatment of bullous pemphigoid and mucous membrane pemphigoid have recently been published.

Socioeconomic Inequalities in Functional Outcome After Reperfusion-Treated Ischemic Stroke.

BACKGROUND: We aimed to investigate whether socioeconomic status (SES) was associated with functional outcome in patients with ischemic stroke treated with reperfusion therapy (intravenous thrombolysis and/or thrombectomy). METHODS: This nationwide cohort study included reperfusion-treated patients with ischemic stroke ≥18 years registered in the Danish Stroke Registry between 2015 and 2018. Functional outcome was determined by the modified Rankin Scale score 90 days after stroke. SES was defined by educational attainment, family income, and employment status before stroke. SES data were available from Statistics Denmark and linked on the individual level with data from the Danish Stroke Registry. Uni- and multivariable ordinal logistic regression was performed for each socioeconomic parameter individually (education, income, and employment) to estimate the common odds ratios (cORs) for lower 90-day modified Rankin Scale scores. RESULTS: A total of 5666 patients were included. Mean age was 68.7 years (95% CI, 68.3-69.0), and 38.4% were female. Low SES was associated with lower odds for achieving lower 90-day modified Rankin Scale score: Low versus high education, cOR, 0.69 (95% CI, 0.61-0.79), low versus high income, cOR, 0.59 (95% CI, 0.53-0.67), and unemployed versus employed, cOR, 0.70 (95% CI, 0.58-0.83). Inequalities were reduced after adjusting for age, sex, and immigrant status, except for unemployed versus employed patients, adjusted cOR, 0.66 (95% CI, 0.54-0.80). No statistically significant differences remained after adjusting for potentially mediating variables (eg, stroke severity, prestroke modified Rankin Scale, and smoking). CONCLUSIONS: Socioeconomic inequalities were observed in functional outcome after reperfusion treated ischemic stroke. In particular, prestroke unemployment was negatively associated with good functional outcome. A more adverse prognostic profile among patients with low SES appeared to explain the majority of these inequalities.

Being a Fair Neighbor-Towards a Psychometric Inventory to Assess Fairness-Related Perceptions of Airports by Residents-Development and Validation of the Aircraft Noise-Related Fairness Inventory (fAIR-In).

Aircraft noise causes a variety of negative health consequences, and annoyance is a central factor mediating stress-related health risks. Non-acoustic factors play an important role in the experience of annoyance where the aspect of fairness is assumed to be a vital component. This paper describes the development of the Aircraft Noise-related Fairness Inventory (fAIR-In) and examines its factorial validity, construct validity and predictive validity. The development of the questionnaire included expert consultations, statements from airport residents and a large-scale online survey around three German airports (N = 1367). Its items cover distributive, procedural, informational and interpersonal fairness. Via mailshot, almost 100,000 flyers were sent out in more (>55 dB(A) Lden)- and less (≤55 dB(A) Lden)-aircraft-noise-exposed areas around Cologne-Bonn, Dusseldorf and Dortmund Airport. Thirty-two items were carefully selected considering reliability, theoretical importance and factor loading calculated via exploratory factor analysis (EFA), with all facets achieving high internal consistency (α = 0.89 to 0.92). The factorial validity, analyzed via a confirmatory factor analysis (CFA), revealed that viewing distributive, procedural, informational and interpersonal fairness as distinct factors produced a better fit to the data than other categorizations with fewer factors. The fAIR-In shows adequate results in terms of construct validity and excellent results in terms of the predictive validity of annoyance by aircraft noise (r = -0.53 to r = -0.68), acceptance of airports and air traffic (r = 0.46 to r = 0.59) and willingness to protest (r = -0.28 to r = -0.46). The fAIR-In provides airport managers with a reliable, valid and easy-to-use tool to design, monitor and evaluate efforts to improve the neighborliness between an airport and its residents.

[Multimorbidity and its Importance in Future Health Care in Germany: a Secondary Data Analysis Based on 67 Million Health Insurance Policy Holders]. / Multimorbidität in Deutschland und ihre Bedeutung für die Versorgung der Zukunft ­ eine Sekundärdatenanalyse basierend auf 67 Mio. Versichertendaten.

BACKGROUND: Multimorbidity is a particular challenge for health care systems. In Germany, epidemiological findings are primarily sample-based. The estimated prevalence among adults in Germany is high, but there are methodological problems, such as a lack of a uniform definition. METHOD: Statutory health insurance data from the information system for health care data ("Informationssystem Versorgungsdaten") of the former German Institute for Medical Documentation and Information were analyzed. A total of 67.3 million people with statutory health insurance in 2014 were included. Multimorbidity was defined by the presence of at least three chronic diseases from a list of 46 diseases per ICD-10. RESULTS: A total of 21,157,937 individuals, or 31.4% of the total cohort, were defined as multimorbid. In men, progression of multimorbidity occurred at the age of about 40 years, whereas the increase was seen at the age of about 35 years in women. The different disease burden varied in different age and sex groups. CONCLUSION: A better understanding of complex disease interactions in relation to age and sex is needed. Interdisciplinary approaches with specific care concepts for multimorbidity, adapted to the chronic care model, should be explored in order to achieve an ideal care situation in Germany.

Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood.

BACKGROUND: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls. METHODS: We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)). RESULTS: We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnon-atopic , aOR = 4.03 [1.20-13.45] vs. controlsatopic ). Conjunctivitis showed a negative association versus controlsatopic (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic . Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters. CONCLUSIONS: The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors.

Obstetric Medicine: the protocol for a prospective three-dimensional cohort study to assess maternity care for women with pre-existing conditions (ForMaT).

Background: Pregnancies in women with pre-existing medical conditions are on the rise. These pregnancies are characterized by an increased rate of maternal and perinatal complications, which can result in higher health care expenditures and altered pregnancy experiences. The purpose of this study is to integrally analyze maternity care for women with pre-existing conditions in the framework of a risk-adapted, interdisciplinary care by recording three substantial parts of maternity care: (1) maternal and perinatal outcome; (2) hospital costs and reimbursements covering the period from preconception counseling or initial antenatal visit to discharge after birth; and (3) women's experience of reproductive choice and becoming a mother in the presence of a pre-existing condition. Methods: In this observational, prospective, longitudinal, and monocentric cohort study, we aim to include a total of 1,500 women over a recruitment period of 15 months. Women registering for care at the Department of Obstetrics and Prenatal Medicine, University Hospital Bonn, Germany, are allocated to three groups based on their health and risk status: women with pre-existing conditions, as well as healthy women with obstetric risk factor and healthy women with a low-risk pregnancy. Participants are observed from time of initial consultation until discharge after birth. Analysis focuses on (1) maternal and perinatal outcome, especially rate of severe maternal and neonatal morbidity; (2) costs and reimbursements; and (3) surveys to capture of women's experience and health-related quality of life during the time of reproductive choice, pregnancy, and childbirth in the presence of pre-existing medical conditions. Discussion: With its complex three-dimensional design, the ForMaT-Trial is aiming to provide a comprehensive analysis of pregnancy and childbirth in women with pre-existing conditions. The results may serve as a basis for counseling and care of these women. By analyzing costs of specialized care, data for discussing reimbursement are generated. Lastly, our results may increase awareness for the perception of reproductive choice, pregnancy and motherhood in this continuously rising population.Clinical trial registration: German Clinical Trials Register, DRKS00030061, October 28, 2022.

Temperature and particulate matter as environmental factors associated with seasonality of influenza incidence - an approach using Earth observation-based modeling in a health insurance cohort study from Baden-Württemberg (Germany).

BACKGROUND: Influenza seasonality has been frequently studied, but its mechanisms are not clear. Urban in-situ studies have linked influenza to meteorological or pollutant stressors. Few studies have investigated rural and less polluted areas in temperate climate zones. OBJECTIVES: We examined influences of medium-term residential exposure to fine particulate matter (PM2.5), NO2, SO2, air temperature and precipitation on influenza incidence. METHODS: To obtain complete spatial coverage of Baden-Württemberg, we modeled environmental exposure from data of the Copernicus Atmosphere Monitoring Service and of the Copernicus Climate Change Service. We computed spatiotemporal aggregates to reflect quarterly mean values at post-code level. Moreover, we prepared health insurance data to yield influenza incidence between January 2010 and December 2018. We used generalized additive models, with Gaussian Markov random field smoothers for spatial input, whilst using or not using quarter as temporal input. RESULTS: In the 3.85 million cohort, 513,404 influenza cases occurred over the 9-year period, with 53.6% occurring in quarter 1 (January to March), and 10.2%, 9.4% and 26.8% in quarters 2, 3 and 4, respectively. Statistical modeling yielded highly significant effects of air temperature, precipitation, PM2.5 and NO2. Computation of stressor-specific gains revealed up to 3499 infections per 100,000 AOK clients per year that are attributable to lowering ambient mean air temperature from 18.71 °C to 2.01 °C. Stressor specific gains were also substantial for fine particulate matter, yielding up to 502 attributable infections per 100,000 clients per year for an increase from 7.49 µg/m3 to 15.98 µg/m3. CONCLUSIONS: Whilst strong statistical association of temperature with other stressors makes it difficult to distinguish between direct and mediated temperature effects, results confirm genuine effects by fine particulate matter on influenza infections for both rural and urban areas in a temperate climate. Future studies should attempt to further establish the mediating mechanisms to inform public health policies.

Predictive Power of MIB-1 vs. Mitotic Count on Progression-Free Survival in Skull-Base Meningioma.

Although meningiomas are mainly non-aggressive and slow-growing tumors, there is a remarkable recurrence rate in a long-term follow-up. Proliferative activity and progression-free survival (PFS) differs significantly among the anatomic location of meningiomas. The aim of the present study was to investigate the predictive power of MIB-1 labeling index and mitotic count (MC) regarding the probability of PFS in the subgroup of skull-base meningiomas. A total of 145 patients were included in this retrospective study. Histopathological examinations and follow-up data were collected. Ideal cut-off values for MIB-1 and MC were ≥4.75 and ≥6.5, respectively. MIB-1 as well as MC were good predictors for PFS in skull-base meningiomas. Time-dependent analysis of MIB-1 and MC in prediction of recurrence of skull-base meningioma showed that their prognostic values were comparable, but different cut-offs for MC should be considered regarding the meningioma's location. As the achievement of a gross total resection can be more challenging in skull-base meningiomas and second surgery implies a higher risk profile, the recurrence risk could be stratified according to these findings and guide decision-making for follow-ups vs. adjuvant therapies.

Comparison of trunk muscle exercises in supine position during short arm centrifugation with 1 g at centre of mass and upright in 1 g.

Spaceflight is associated with reduced antigravitational muscle activity, which results in trunk muscle atrophy and may contribute to post-flight postural and spinal instability. Exercise in artificial gravity (AG) performed via short-arm human centrifugation (SAHC) is a promising multi-organ countermeasure, especially to mitigate microgravity-induced postural muscle atrophy. Here, we compared trunk muscular activity (mm. rectus abdominis, ext. obliques and multifidi), cardiovascular response and tolerability of trunk muscle exercises performed during centrifugation with 1 g at individual center of mass on a SAHC against standard upright exercising. We recorded heart rate, blood pressure, surface trunk muscle activity, motion sickness and rating of perceived exertion (BORG) of 12 participants (8 male/4 female, 34 ± 7 years, 178.4 ± 8.2 cm, 72.1 ± 9.6 kg). Heart rate was significantly increased (p < 0.001) during exercises without differences in conditions. Systolic blood pressure was higher (p < 0.001) during centrifugation with a delayed rise during exercises in upright condition. Diastolic blood pressure was lower in upright (p = 0.018) compared to counter-clockwise but not to clockwise centrifugation. Target muscle activation were comparable between conditions, although activity of multifidi was lower (clockwise: p = 0.003, counter-clockwise: p < 0.001) and rectus abdominis were higher (clockwise: p = 0.0023, counter-clockwise: < 0.001) during centrifugation in one exercise type. No sessions were terminated, BORG scoring reflected a relevant training intensity and no significant increase in motion sickness was reported during centrifugation. Thus, exercising trunk muscles during centrifugation generates comparable targeted muscular and heart rate response and appears to be well tolerated. Differences in blood pressure were relatively minor and not indicative of haemodynamic challenge. SAHC-based muscle training is a candidate to reduce microgravity-induced inter-vertebral disc pathology and trunk muscle atrophy. However, further optimization is required prior to performance of a training study for individuals with trunk muscle atrophy/dysfunction.

Specialized Outpatient Palliative Care­Clinical Course and Predictors for Living at Home Until Death

BACKGROUND: Specialized outpatient palliative care (SOPC) is an important component of the palliative medicine care concept in Germany. Its purpose is to improve the out-of-hospital care of patients who cannot be adequately cared for by their primary care physicians and in the setting of general outpatient palliative care (GOPC). METHODS: In this retrospective analysis of anonymized routine treatment data, we analyzed the characteristics of SOPC patients overall and with specific diseases, and depicted them both numerically and graphically. We also carried out a regression analysis of the factors affecting whether or not patients will be able to die in a home environment. RESULTS: The analysis included data from 14 460 patients who were treated by 14 different SOPC teams in the North Rhine area of Germany in 2017 and 2018. The majority of patients who died were able to live at home until death (85.9%); only a small percentage died as inpatients (7.7%). The symptom burden shortly before death was less than at the beginning of treatment. The factors displaying a statistically significant association with dying at home were: more advanced age (aOR 0.96; 95% CI: [0.95; 0.96]), female sex (aOR 0.85; 95% CI: [0.74; 0.98]), and house calls at night (aOR 0.60; 95% CI: [0.51; 0.71]). CONCLUSION: SOPC met its declared objectives of limiting distressing symptoms and enabling patients to live at home until death.

Red Blood Cell Distribution Width to Platelet Count Ratio Facilitates Preoperative Prediction of Recurrence in Surgically Treated Chronic Subdural Hematoma.

Objective: Recent studies have demonstrated emerging evidence of the role of inflammation in the growth and recurrence of chronic subdural hematoma (cSDH). Red blood cell distribution width to platelet count ratio (RPR) is a novel biomarker for inflammation in cancer, cardiac, and inflammatory diseases. The present retrospective study investigated the impact of RPR on recurrence after burr hole surgery for cSDH in 297 patients. Methods: The optimal cut-off value for RPR was defined as ≥0.0568 according to the receiver operating characteristic curve (AUC:0.64, 95%CI:0.55-0.72, p = 0.007). The study cohort was dichotomized into low (n = 157) and high (n = 140) RPR groups. Results: Significant differences between the groups were identified regarding American Society of Anesthesiologists (ASA) classification and frequency of anticoagulant intake. Demographics, comorbidities, size, morphology, and mass effect of cSDH were homogeneously distributed among the RPR groups. Multivariable binary logistic regression analysis considering location, midline-shift, septation, RPR, anticoagulant intake, sex, and ASA classification revealed that an increased baseline RPR (≥0.0568, OR: 3.1, 95%CI: 1.4-6.8, p = 0.004), and preoperative midline-shift (≥5 mm, OR: 2.7, 95%CI: 1.3-6.0, p = 0.01) are independent predictors of recurrent cSDH. Conclusion: The present findings suggest RPR as a novel inflammatory biomarker enabling risk stratification of recurrence after burr hole surgery for cSDH and might facilitate tailored medical decision making.