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CONFIDENCE treatment success: long-term real-world effectiveness and safety of ocrelizumab in Germany
No full textBackground Early high-efficacy treatment for people with relapsing multiple sclerosis (pwRMS) may provide better long-term outcomes compared with the escalation strategy. In this study, we present an analysis of treatment success and safety from the CONFIDENCE study in a real-world cohort of pwRMS treated with ocrelizumab in different treatment lines for up to 5.5 years. Methods The ongoing German non-interventional post-authorization safety study, CONFIDENCE (ML39632, EUPAS22951), evaluates the long-term safety and effectiveness of therapy in pwMS newly treated with ocrelizumab or other disease-modifying therapies for up to 10 years. This analysis presents CONFIDENCE treatment success (proportion of people with no clinical disease activity measured by relapse or disease progression and no treatment discontinuation due to adverse event [AE] or lack of therapeutic effectiveness), confirmed disability progression (CDP), annualized relapse rates, and safety in pwRMS stratified by the number of previous MS therapies (PMSTs). Results At the data cutoff (11 October 2023), the full analysis set included 2,261 pwRMS treated with ≥1 dose of ocrelizumab. At baseline, the mean age (SD) of the participants was 41.16 (11.39) years (treatment-naïve, 39.19 [12.95] years; ≥3 PMSTs, 42.80 [10.08] years), and the mean Expanded Disability Status Scale (EDSS) score was 3.08 (1.86) (treatment-naïve, 2.37 [1.54]; ≥3 PMSTs, 3.57 [1.90]). Overall, 58.4% of pwRMS with continuous treatment achieved CONFIDENCE treatment success from baseline until year 5 (74.0 and 50.3% of pwRMS with 0 and ≥3 PMSTs). The main reasons for not achieving CONFIDENCE treatment success were relapse and CDP, while treatment discontinuation due to AEs or lack of effectiveness played a minor role. The proportion of pwRMS with AEs did not increase with longer treatment duration and tended to be higher with more PMSTs. The spectrum of AEs was similar across treatment lines, and no new or unexpected AEs were observed. Conclusion CONFIDENCE treatment success remained high over 5 years of ocrelizumab treatment, even among people with RMS (pwRMS) with a higher number of PMSTs. Only a small proportion of pwRMS discontinued treatment due to AEs. These results support early intervention with high-efficacy ocrelizumab treatment to optimize long-term outcomes for pwRMS. Trial registration https://catalogues.ema.europa.eu/node/3142/administrative-details , identifiers ML39632 and EUPAS22951
Genomic Characterization of Carbapenem-Resistant Acinetobacter baumannii (OXA-23) and Klebsiella pneumoniae (KPC-2) Causing Hospital-Acquired Infections in Dogs
No full textBackground/Objectives: Antimicrobial resistance is a major global health threat. Among the most problematic pathogens are carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, which are significant causes of mortality in humans, particularly in the context of nosocomial infections. In companion animals, these bacteria have been reported mainly as colonizers of healthy animals or, less frequently, in community-acquired infections. However, no confirmed cases of healthcare-associated infections caused by these species have been documented in this population. This study reports the first confirmed fatal cases of infection with carbapenem-resistant A. baumannii and KPC-producing K. pneumoniae in dogs. Methods: Three hospitalized dogs developed infections associated with distinct anatomical devices, including a venous catheter, an endotracheal tube, and a Penrose drain. Bacterial isolation followed by antimicrobial susceptibility testing identified carbapenem-resistant A. baumannii and K. pneumoniae. The isolates were subsequently subjected to additional antimicrobial resistance tests and whole-genome sequencing (WGS). Results: WGS confirmed the presence of the OXA-23 carbapenemase gene in both A. baumannii isolates and the KPC-2 carbapenemase gene was detected in the K. pneumoniae strain. All three strains exhibited resistance to multiple antimicrobial classes, including β-lactams (amoxicillin-clavulanic acid, ampicillin, cephalotin, piperacillin-tazobactam, cefoxitin, ceftiofur, cefotaxime, ertapenem, imipenem and meropenem), aminoglycosides (gentamicin, neomycin), tetracyclines (doxycycline, tetracycline and oxytetracycline), fluoroquinolones (ciprofloxacin, enrofloxacin), and folate pathway antagonists (trimethoprim-sulfamethoxazole). Multilocus sequence typing identified two high-risk clones: K. pneumoniae ST340 (CC258) and A. baumannii ST15 (CC15). Single nucleotide polymorphism analysis confirmed a high degree of genetic similarity between these isolates and strains previously associated with human infections in Brazil. Conclusions: These findings provide the first evidence of fatal, healthcare-associated infections caused by these multidrug-resistant pathogens in dogs and underscore the need to strengthen surveillance and infection control practices in veterinary hospitals. Furthermore, the results raise concerns about the potential of companion animals to act as reservoirs for multidrug-resistant organisms of public health relevance
Who Are the Farmers Participating in a Carbon Sequestration Program? Results of a Discrete Choice Experiment in Germany
No full textABSTRACT Agricultural soils offer great potential for carbon sequestration through humus formation. One way to motivate farmers to build up humus is through humus programs. These are still at an early stage of development, poorly explored, and the number of participating farmers is low. Our aim is to explain the heterogeneity of farmers' willingness to participate in humus programs by typologizing them according to different design preferences and socioeconomic backgrounds. To this end, we conducted a survey with German farmers including a discrete choice experiment and questions about environmental awareness, profit orientation and farm characteristics. We summarized farmers' attitudes towards for example, climate change with a factor analysis and included the results into the latent class model we used to analyze the discrete choice experiment. The farmers surveyed can be divided into four classes. The results show that the classes differ in the farmers' preferences for the characteristics of a humus program, for example, type of reference value and program duration, and according to the factors of the factor analysis, for example, advocacy of humus programs. The classes distinguish between disinterested and motivated farmers, farmers focusing on safe money and farmers focusing on quick money. With this study, we improve the understanding of farmers' acceptance of humus programs, which is essential before starting targeted (political) efforts
Mixed broadleaf–conifer forests promote coexistence of red squirrels and dormice
No full textAbstract Tree species admixtures are a promising management practice to reconcile biodiversity and economic benefits. Mixtures have been shown to promote the diversity of many taxa. However, how canopy-dwelling small mammals are affected by tree admixtures and changes in forest composition has seldom been studied. Here we assess how forests with varying proportions of European beech ( Fagus sylvatica ) and two conifer species: ( Pseudotsuga menziesii and Picea abies) influence the presence of three arboreal small mammals: red squirrel (Sciurus vulgaris), edible dormouse ( Glis glis ) and hazel dormouse ( Muscardinus avellanarius ). We set up 80 non-baited camera trap stations on trees, at heights ranging from 2 to 30 m, at four sites (with five forest plots each) in northern Germany. We then assessed arboreal small mammal species’ presence, occupancy, potential competition, and probability of co-occurrence through occupancy models and generalized linear mixed models. After 7374 camera-days, we recorded 468 sightings of red squirrels, 249 of edible dormice, and 197 of hazel dormice. We found no evidence that the presence of one animal species negatively influenced the presence of the others. Forests with a greater share of conifers had greater occupancy by squirrels, while forests with greater beech share had greater occupancy by dormice species. The probability of co-occurrence of arboreal small mammal species was the highest in forests with intermediate proportions of beech and conifers, revealing that mixed forests promoted the coexistence of red squirrels and dormice. Clinical trial number : Not applicable
Behavioral climate change: does thinking about future consequences of climate change affect risk preferences and cooperation?
No full textAbstract Human-made climate change is one of the most pressing challenges of the 21st century. This paper examines how thinking about future consequences of climate change influences decision-making. Using priming experiments, we address ambiguity preferences, risk preferences, and willingness to cooperate among farmers, students, and representatives of the general population of Germany. The results show that farmers (who were asked specifically about the consequences for their profession) – but not students or representatives of the general population – increase their investments in uncertain assets. There are also common patterns across the subject pools, most notably willingness to cooperate remains largely unchanged
Radiotherapy for patients with brain metastases and leptomeningeal carcinomatosis: prognostic factors and clinical outcomes
No full textAbstract Brain metastases and leptomeningeal carcinomatosis (LC) are complications of advanced-stage malignancies, associated with a poor prognosis. This study aimed to evaluate the role of prognostic factors and radiotherapy (RT) treatment approaches while taking toxicity into account. We performed a retrospective study and compared clinical characteristics, prognostic factors, toxicities and outcomes in patients with (1) parenchymal brain metastases (PM) ( n = 275) vs. LC ( n = 35) and (2) in patients with whole brain radiotherapy (WBRT) ( n = 52) vs. WBRT + boost ( n = 201). We found poorer survival (OS) of the LC group compared to PM patients in univariable analysis (not in multivariable analysis). LC patients predominantly underwent WBRT only, received surgical resection before RT less frequently and had more RT discontinuations than PM patients. OS was better in the WBRT + boost group than in the WBRT only group. In patients who received WBRT + boost, the primary tumor was more often controlled, and the number of PM was lower compared to the WBRT only group. WBRT + boost was associated with higher rates of alopecia than WBRT only. Patients with LC had a worse prognosis compared to patients with PM. WBRT + boost resulted in higher toxicity than WBRT only but resulted in better OS in the presented study. WBRT + boost patients had more favorable prognostic factors prior to RT, so OS improvement is not likely due to boost. Treating brain metastases requires a careful assessment of benefits and risks. Optimal RT planning should consider prognostic factors and potential side effects individually
The effect of antibiotic therapy on clinical outcome in patients hospitalized with moderate COVID-19 disease: a prospective multi-center cohort study
No full textAbstract Purpose The benefit of antibiotic treatment (ABT) for patients with moderate COVID-19 is unclear and overtreatment poses the risk of adverse effects such as Clostridioides difficile infection and antibiotic resistance. This multi-center study compares health status improvement between patients with and without ABT at hospital admission. Methods Between March 2020 and May 2023, hospitalized adults with confirmed SARS-CoV-2 infection were recruited from the German National Pandemic Cohort Network (NAPKON), which includes patients from various hospitals across Germany. The study population included patients with moderate or severe COVID-19 at baseline. The primary objective was to compare health improvement or decline after two weeks between patients who received ABT at baseline and those who did not in the moderate COVID-19 population. The statistical analysis adjusted for confounders such as gender, age, vaccination status, clinical condition, and comorbidities. The severe COVID-19 population was investigated as a secondary objective. Results A total of 1,317 patients (median age 59 years; 38% women) were eligible for analysis, of whom 1,149 had moderate and 168 severe COVID-19 disease. ABT for pneumonia was administered to 467 patients with moderate and 117 with severe COVID-19. ABT at baseline was significantly associated with a higher deterioration rate after two weeks in patients with moderate COVID-19 (ABT: 292 improvement, 61 deterioration; no ABT: 429 improvement, 14 deterioration). A similar result was obtained in the multiple regression analysis where an odds ratio of 5.00 (95% confidence interval: 2.50 – 10.93) for ABT was observed. Conclusion We found no benefit of antibiotic therapy in patients with moderate COVID-19. Use of ABT was associated with a higher likelihood of clinical deterioration. Graphical abstrac
Real-World Harm Reduction of Metformin Plus DPP4 Inhibitors versus Metformin Plus Sulfonylureas in Older Adults: A Target Trial Emulation Using German Claims Data
No full textTowards an improved representation of the relationship between root traits and nitrogen losses in process-based models
No full texthttp://dx.doi.org/10.13039/501100011958 Danmarks Frie Forskningsfondhttp://dx.doi.org/10.13039/501100004836 Independent Research Fund Denmar
Host cell entry and neutralisation sensitivity of SARS-CoV-2 BA.3.2
No full texthttp://dx.doi.org/10.13039/100018696 HORIZON EUROPE Healthhttp://dx.doi.org/10.13039/501100023651 European Social Fund for Germanyhttp://dx.doi.org/10.13039/100011937 Lower Saxony State Ministry of Science and Culturehttp://dx.doi.org/10.13039/501100002745 Bavarian Research Foundationhttp://dx.doi.org/10.13039/501100001659 German Research Foundationhttp://dx.doi.org/10.13039/501100002347 Federal Ministry of Education and Research Bonn Offic