Der Einfluss psychischer Faktoren auf die Bewältigung der chronisch obstruktiven Lungenerkrankung (COPD)

Die chronisch obstruktive Lungenerkrankung (COPD) ist eine der häufigsten chronischen Erkrankungen. COPD verläuft progredient und ist gekennzeichnet durch Atemnot, Husten und Auswurf. Die körperliche Symptomatik bedingt eine starke Beeinträchtigung für die Betroffenen, die mit einer geringen Lebensqualität und häufigen komorbiden psychischen Symptomen (z.B. krankheitsspezifischen Ängsten) oder psychischen Störungen einhergeht. Mit medizinischen Behandlungsmöglichkeiten kann aktuell keine vollständige Symptomreduktion erreicht werden. Aus diesem Grund und aufgrund der chronisch progredienten Natur der Erkrankung soll die Behandlung vor allem die Lebensqualität der Betroffenen erhalten. Ziel dieser Dissertation war, psychische Faktoren und deren Zusammenhänge zur gesundheitsspezifischen Lebensqualität zu untersuchen, die für die Krankheitsbewältigung nachteilig (z.B. krankheitsspezifische Ängste) oder vorteilhaft (protektive Faktoren) sind. In einer querschnittlichen Studie untersuchten wir die Hypothese, dass krankheitsspezifische Ängste in einem Zusammenhang mit der gesundheitsspezifischen Lebensqualität stehen (Studie 1). Zur besseren Erfassung dieser COPD-spezifischen Ängste wurde ein psycho-metrisches Instrument weiterentwickelt und an einer großen Stichprobe von COPD-Betroffenen untersucht. Wie erwartet gingen krankheitsspezifische Ängste mit einer geringeren gesundheitsspezifischen Lebensqualität einher. Dieser Zusammenhang zeigte sich regressionsanalytisch, nachdem u.a. psychische Symptome allgemeiner Ängstlichkeit und Depressivität, das Krankheitsstadium, Alter und Geschlecht berücksichtigt wurden. Mit zunehmender Krankheitsschwere berichteten die Betroffenen mehr krankheitsspezifische Ängste und geringere gesundheitsspezifische Lebensqualität. In einer weiteren querschnittlichen Studie untersuchten wir den Einfluss möglicher protektiver psychischer Faktoren auf die gesundheitsspezifische Lebensqualität sowie auf komorbide psychische Angst- und Depressionssymptome (Studie 2). Dabei wurden zwei Konzepte untersucht, die Prozesse inneren Wachstums darstellen und Persönlichkeitsmerkmale abbilden sollen, die Anpassungsprozesse an Stressoren und Lebensumstände begünstigen: Kohärenzsinn und Resilienz. Die regressionsanalytische Untersuchung ergab, dass mehr Kohärenzsinn und Resilienz mit einer größeren gesundheitsspezifischeren Lebensqualität sowie weniger Angst- und Depressionssymptomatik einhergingen. Zunehmende Krankheitsschwere ging mit einer geringeren gesundheitsspezifischen Lebensqualität und mehr Depressionssymptomatik einher, aber nicht mit mehr Angstsymptomatik. In einer Übersichtsarbeit wurden psychische Faktoren zusammengestellt, die in der COPD-Behandlung im Rahmen von pneumologischen Rehabilitationsmaßnahmen für die Krankheitsbewältigung relevant sind (Studie 3). Zusammenfassend zeigte sich, dass die gefundenen Faktoren dazu beitrugen, dass sich die Behandlungsergebnisse zwischen den Patienten stark unterschieden. Da pneumologische Rehabilitationsmaßnahmen ein zentraler Behandlungsbaustein bei COPD sind, wirken sie sich auf die Krankheitsbewältigung und damit ebenfalls auf die gesundheitsspezifische Lebensqualität aus. Die durchgeführten Studien betonten die Bedeutung psychischer Faktoren auf die Krankheitsbewältigung, da sie Zusammenhänge zwischen krankheitsspezifischen Ängsten, protektiven und anderen psychischen Faktoren zur gesundheitsspezifischen Lebensqualität ergaben. Es wird diskutiert, wie sich diese Erkenntnisse bewerten, Forschungsansätze vertiefen und Behandlungsmöglichkeiten ableiten lassen

Effect of terroir on the glucosinolate content of Moringa oleifera grown in three agro-ecological zones of Ghana

Environmental factors and cultural practices significantly influence the secondary metabolites in plants, e.g., glucosinolates, depending on the cultivar of each species. The present study analyzed the influence of specific environmental factors (e.g., temperature, rainfall, and relative humidity), elevation, and fertilization (i.e., nitrogen and sulfur) on the glucosinolate content in leaves of wild-grown Moringa oleifera from three agro-ecological zones in Ghana and selected M.oleifera accessions cultivated under semi-controlled field conditions. The results showed that climate did not significantly influence total glucosinolate content in leaves of both wild-grown and cultivated accessions of M.oleifera, while elevation significantly influenced the total glucosinolate content of wild-grown plants. Fertilization had no significant impact on the total glucosinolate content of the cultivated accessions. Furthermore, wild-collected M.oleifera leaves from the three agro-ecological zones did not reveal a significant difference in their total glucosinolate content. For the cultivated accessions of M.oleifera, the agro-ecological zone, harvest time, and accession and the interactions among these factors significantly influenced the total glucosinolate content. The results suggest that selecting suitable accessions, choosing suitable locations, and applying appropriate cultivation practices could contribute to optimizing the production of health-promoting Moringa plants with special emphasis on glucosinolate content

Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial

Background Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. Methods This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1–3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1–7), and prednisone (40 mg/m2 orally on days 1–14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). Findings Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24–42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65–0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45–0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6–96·1) for BrECADD and 90·9% (88·7–93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7–99·5) and 98·2% (97·2–99·3), respectively. Interpretation BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma

Associations of Migration, Socioeconomic Position and Social Relations With Depressive Symptoms – Analyses of the German National Cohort Baseline Data

Objectives: We analyze whether the prevalence of depressive symptoms differs among various migrant and non-migrant populations in Germany and to what extent these differences can be attributed to socioeconomic position (SEP) and social relations.Methods: The German National Cohort health study (NAKO) is a prospective multicenter cohort study (N = 204,878). Migration background (assessed based on citizenship and country of birth of both participant and parents) was used as independent variable, age, sex, Social Network Index, the availability of emotional support, SEP (relative income position and educational status) and employment status were introduced as covariates and depressive symptoms (PHQ-9) as dependent variable in logistic regression models.Results: Increased odds ratios of depressive symptoms were found in all migrant subgroups compared to non-migrants and varied regarding regions of origins. Elevated odds ratios decreased when SEP and social relations were included. Attenuations varied across migrant subgroups.Conclusion: The gap in depressive symptoms can partly be attributed to SEP and social relations, with variations between migrant subgroups. The integration paradox is likely to contribute to the explanation of the results. Future studies need to consider heterogeneity among migrant subgroups whenever possible

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Knowledge Augmented Machine Learning with Applications in Autonomous Driving: A Survey

The existence of representative datasets is a prerequisite of many successful artificial intelligence and machine learning models. However, the subsequent application of these models often involves scenarios that are inadequately represented in the data used for training. The reasons for this are manifold and range from time and cost constraints to ethical considerations. As a consequence, the reliable use of these models, especially in safety-critical applications, is a huge challenge. Leveraging additional, already existing sources of knowledge is key to overcome the limitations of purely data-driven approaches, and eventually to increase the generalization capability of these models. Furthermore, predictions that conform with knowledge are crucial for making trustworthy and safe decisions even in underrepresented scenarios. This work provides an overview of existing techniques and methods in the literature that combine data-based models with existing knowledge. The identified approaches are structured according to the categories integration, extraction and conformity. Special attention is given to applications in the field of autonomous driving

Critical evaluation of molecular tumour board outcomes following 2 years of clinical practice in a Comprehensive Cancer Centre

Recently, molecular tumour boards (MTBs) have been integrated into the clinical routine. Since their benefit remains debated, we assessed MTB outcomes in the Comprehensive Cancer Center Ostbayern (CCCO) from 2019 to 2021. Methods and results In total, 251 patients were included. Targeted sequencing was performed with PCR MSI-evaluation and immunohistochemistry for PD-L1, Her2, and mismatch repair enzymes. 125 treatment recommendations were given (49.8%). High-recommendation rates were achieved for intrahepatic cholangiocarcinoma (20/30, 66.7%) and gastric adenocarcinoma (10/16, 62.5%) as opposed to colorectal cancer (9/36, 25.0%) and pancreatic cancer (3/18, 16.7%). MTB therapies were administered in 47 (18.7%) patients, while 53 (21.1%) received alternative treatment regimens. Thus 37.6% of recommended MTB therapies were implemented (47/125 recommendations). The clinical benefit rate (complete + partial + mixed response + stable disease) was 50.0% for MTB and 63.8% for alternative treatments. PFS2/1 ratios were 34.6% and 16.1%, respectively. Significantly improved PFS could be achieved for m1A-tier-evidence-based MTB therapies (median 6.30 months) compared to alternative treatments (median 2.83 months; P = 0.0278). Conclusion The CCCO MTB yielded a considerable recommendation rate, particularly in cholangiocarcinoma patients. The discrepancy between the low-recommendation rates in colorectal and pancreatic cancer suggests the necessity of a weighted prioritisation of entities. High-tier recommendations should be implemented predominantly

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis