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Background: Adjuvant treatment options have become the standard therapy for stage III and IV resectable cutaneous melanoma. Two recent studies led to the registration of dabrafenib and trametinib as targeted therapies for BRAF-mutated melanoma, and of immunotherapy with nivolumab irrespective of BRAF-mutation status. Both therapies have different spectrums of adverse events. Objective: To estimate the financial impact of side effects from the perspective of the German statutory sick funds to compare both therapeutic options and to relate the burden to the overall costs of the treatment. Study design and setting: Thirty-six adverse event categories for the combination of dabrafenib and trametinib ('combi treatment') and for nivolumab were extracted from the original publications of the studies named COMBI-AD and CheckMate 238. Patients and intervention: For all event categories a diagnosis and therapy recommendation were determined according to current national or international guidelines or from leading German textbooks. Main outcome measure: The resulting diagnostic steps, treatments, and therapies were evaluated with unit costs based on the German fee schedule for ambulatory physicians, the German G-DRG scheme, and the German drug price list. Results: The number of events with nivolumab per one hundred treatments amounted to 3.8 mandatory hospitalizations, 3.5 emergency care events and 0.8 life-threatening events. For the combi treatment, the respective number of events per one hundred treatments was 2.7, 1.8, and 0.5. The overall cost burden was calculated as €899 for nivolumab and €861 for combi-treatment. Conclusion: The treatment of adverse events resulting from adjuvant melanoma therapy showed comparable costs for both therapies. [ABSTRACT FROM AUTHOR]

Purpose: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB., Methods: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points., Results: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously., Conclusion: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries., (© 2024. The Author(s).)

Objectives: To investigate, whether inflammatory rheumatic diseases (IRD) inpatients are at higher risk to develop a severe course of SARS-CoV-2 infections compared to the general population, data from the German COVID-19 registry for IRD patients and data from the Lean European Survey on SARS-CoV-2 (LEOSS) infected patients covering inpatients from the general population with SARS-CoV-2 infections were compared., Methods: 4310 (LEOSS registry) and 1139 cases (IRD registry) were collected in general. Data were matched for age and gender. From both registries, 732 matched inpatients (LEOSS registry: n = 366 and IRD registry: n = 366) were included for analyses in total., Results: Regarding the COVID-19 associated lethality, no significant difference between both registries was observed. Age > 65°years, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, spondyloarthritis and the use of rituximab were associated with more severe courses of COVID-19. Female gender and the use of tumor necrosis factor-alpha inhibitors (TNF-I) were associated with a better outcome of COVID-19., Conclusion: Inflammatory rheumatic diseases (IRD) patients have the same risk factors for severe COVID-19 regarding comorbidities compared to the general population without any immune-mediated disease or immunomodulation. The use of rituximab was associated with an increased risk for severe COVID-19. On the other hand, the use of TNF-I was associated with less severe COVID-19 compared to the general population, which might indicate a protective effect of TNF-I against severe COVID-19 disease., Competing Interests: TW was employed by company Biocontrol Jena. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Hasseli, Hanses, Stecher, Specker, Weise, Borgmann, Hasselberger, Hertenstein, Hower, Hoyer, Koll, Krause, von Lilienfeld-Toal, Lorenz, Merle, Nunes de Miranda, Pletz, Regierer, Richter, Rieg, Roemmele, Ruethrich, Schmeiser, Schulze-Koops, Strangfeld, Vehreschild, Voit, Voll, Vehreschild, Müller-Ladner and Pfeil.)

To understand and handle the COVID-19 pandemic, digital tools and infrastructures were built in very short timeframes, resulting in stand-alone and non-interoperable solutions. To shape an interoperable, sustainable, and extensible ecosystem to advance biomedical research and healthcare during the pandemic and beyond, a short-term project called "Collaborative Data Exchange and Usage" (CODEX+) was initiated to integrate and connect multiple COVID-19 projects into a common organizational and technical framework. In this paper, we present the conceptual design, provide an overview of the results, and discuss the impact of such a project for the trade-off between innovation and sustainable infrastructures.

Objective: To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe., Methods: This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case-control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching., Results: A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure., Conclusions: This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections. Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Collaboration among logistics facilities in a multicenter logistics delivery network can significantly improve the utilization of logistics resources through resource sharing including logistics facilities, vehicles, and customer services. This study proposes and tests different resource sharing schemes to solve the optimization problem of a collaborative multicenter logistics delivery network based on resource sharing (CMCLDN-RS). The CMCLDN-RS problem aims to establish a collaborative mechanism of allocating logistics resources in a manner that improves the operational efficiency of a logistics network. A bi-objective optimization model is proposed with consideration of various resource sharing schemes in multiple service periods to minimize the total cost and number of vehicles. An adaptive grid particle swarm optimization (AGPSO) algorithm based on customer clustering is devised to solve the CMCLDN-RS problem and find Pareto optimal solutions. An effective elite iteration and selective endowment mechanism is designed for the algorithm to combine global and local search to improve search capabilities. The solution of CMCLDN-RS guarantees that cost savings are fairly allocated to the collaborative participants through a suitable profit allocation model. Compared with the computation performance of the existing nondominated sorting genetic algorithm-II and multi-objective evolutionary algorithm, AGPSO is more computationally efficient. An empirical case study in Chengdu, China suggests that the proposed collaborative mechanism with resource sharing can effectively reduce total operational costs and number of vehicles, thereby enhancing the operational efficiency of the logistics network., Competing Interests: The authors have declared that no competing interests exist.

Conclusion: Retropharyngeal abscess (RPA) is a rare, potentially life-threatening disease, requiring appropriate otorhinolaryngologic as well as radiologic diagnostics, and medical and surgical intervention by a transoral, transcervical or transnasal approach in a multidisciplinary setting., Objectives: The risks and benefits of surgical intervention in patients with RPA were assessed. The main outcome measure was the clinical resolution of the abscess., Patients and Methods: A retrospective chart review was performed at a tertiary care university hospital over a period of 28 months. Eleven patients aged 1 to 68 years with the diagnosis of RPA were included., Results: All patients presented with restricted cervical mobility and all patients had CT and/or MRI scan on admission. The mean abscess volume was 9.4 cm(3). Surgical intervention was performed in all cases, including transoral (n=5), transcervical (n=3) or combined transoral and transcervical (n=2) drainage. In one patient RPA close to the skull base was drained by an MRI-guided transnasal approach. All patients recovered; however, there was one recurrence and in one case surgical tracheotomy was unavoidable during the course of disease. Growth of streptococcal species was verified in six of the examined abscesses. Abscessing lymphadenitis, infection of a cervical cyst, and previous ganglionar local opioid analgesia treatment were identified as causative factors.

The lipid lowering agent ezetimibe (EZ) and its intestinally formed glucuronide (GLUC) were shown to be substrates of the efflux transporters P-glycoprotein (P-gp) and the multidrug resistance associated protein 2 (MRP2) which markedly influences the disposition and efficacy of EZ in man. This study aims to elucidate the unique meaning of P-gp in the pharmacokinetics of EZ in mice. In brief, serum concentrations, organ distribution and elimination of EZ were determined in 10 male wild-type and mdr1a/b (-/-) mice after oral treatment with EZ (10 mg/kg, 10 days). EZ and GLUC were quantified in serum, urine, feces and various tissues using a validated LC-MS/MS method. Compared to wild-type mice, mdr1a/b knockout was associated with significantly increased serum concentrations of GLUC (5.58 +/- 2.07 versus 2.09 +/- 0.83 ng/ml, p < 0.001) but not of EZ (0.92 +/- 0.73 versus 0.55 +/- 0.40 ng/ml, n.s.). Consequently, urinary excretion of GLUC was about three-fold increased (9.96 +/- 0.27 versus 3.10 +/- 1.37 microg/day, p = 0.049) whereas renal clearance and the amount excreted via feces remained unchanged. Both EZ and GLUC were not over-proportionally distributed into investigated organs. P-glycoprotein primary influences the oral absorption of ezetimibe in mice. Distribution, renal and fecal excretion of the drug seems not to be markedly affected by P-glycoprotein., ((c) 2007 Wiley-Liss, Inc.)

The purpose of this study was to determine the maximum tolerated dose, toxicity profile and anti-tumor activity of paclitaxel in combination with gemcitabine when administered to patients with unresectable locally recurrent or metastatic squamous cell carcinoma of the head and the neck (SCCHN). Twenty-seven patients were treated in a phase I-II study with gemcitabine at a dose of 800 mg/m on days 1 and 8, escalating to a dose of 1,000 mg/m, plus escalating doses of paclitaxel (100, 135 and 175 mg/m) on day 2. Treatment consisted of 6 cycles repeated every 3 weeks. The main toxicity was myelosuppression. Other toxicities were mild and manageable. Due to grade 4 neutropenia at higher doses the recommended dose level of the gemcitabine/paclitaxel combination was 1,000/135 mg/m. Four patients achieved a partial response and no patient had a complete remission, giving an overall response rate of 14.8%. The median time of survival was 24 weeks. We conclude that the combination of paclitaxel and gemcitabine is tolerated, but shows insufficient clinical activity in patients with recurrent and/or metastatic SCCHN to warrant further testing.