Vifor Pharma (Switzerland)

<bold>Background:</bold> Respiratory tract infections (RTI) are a major cause of morbidity and mortality, with direct and indirect economic costs. OM-85 (Broncho-Vaxom®), an extract of bacterial lysates marketed for 45 years for the prevention of recurrent RTIs, has been extensively studied in interventional trials. However, properly designed real-world evidence (RWE) studies supporting its effectiveness in routine practice remain scarce. REACH is the first multi-country, non-interventional study to evaluate OM-85 for the prevention of recurrent RTIs in children and adults. <bold>Methods:</bold> This study utilizes data from two European (THIN Belgium and THIN Italy) and one Chinese (Inspur) databases. Its design was framed using the target trial emulation strategy and published on the EMA RWE catalogue. Exposure groups consist of patients aged ≥ 1 year with at least 2 RTI in the previous year, either initiating OM-85, or non-users, matched based on propensity score. The rate of RTI episodes will be assessed at 3, 6, 9, 12 and 24 months. Secondary outcomes will include demographics, OM-85 prescription patterns, utilization of antibiotics and other concomitant medication. <bold>Results and Conclusion:</bold> A feasibility assessment estimated the number of patients treated with OM-85 at 17,000 in THIN databases and 6,000 in Inspur, warranting broad sample sizes. Prescription details, comorbidities, concomitant medication, and RTI episodes were retrievable. Therefore, this study will provide a deeper understanding of the use of OM-85 in routine practice and its effectiveness in diverse patient populations.

The US Magnet Development Program is leading an effort to design and manufacture a 20 T accelerator dipole magnet. Various designs are under development featuring cos-theta, block-coil, or common-coil geometries. To achieve the target field while maintaining cost-effectiveness the magnet cross-section includes high-temperature superconductor (HTS) inner coils and Nb<inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$_{3}$</tex-math></inline-formula>Sn outer coils, which are all powered in series. The quench protection of this class of high-field accelerator magnets is extremely challenging due to the high energy density, high current density, slow quench propagation, in particular in the HTS coils, and highly inhomogeneous thermal properties of HTS and Nb<inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$_{3}$</tex-math></inline-formula>Sn coils. The magnet quench discharge is simulated with the STEAM-LEDET program as coupled electro-magnetic and thermal transients. The peak temperature and voltage to ground in the magnet coils during the transient are presented. The performance of a CLIQ-based quench protection system applied to 1 m long model magnets in terms of peak temperature and voltage to ground is investigated. Furthermore, the scalability of the proposed solution to full-scale, 15 m long magnets is discussed.

Background and Objectives Chronic Kidney Disease-associated Pruritus (CKD-aP) is a disabling condition that affects around 60% of patients with end-stage kidney disease undergoing dialysis. Current off-label treatment options are neither effective nor appropriate for all dialysis patients, leaving a clear unmet need. This study aimed to evaluate the cost-effectiveness of difelikefalin – the only drug approved in Europe for the treatment of moderate to severe CKD-aP adult patients in haemodialysis – compared to the best supportive care (BSC) from the Spanish NHS perspective. Methods A Markov model was developed with seven health states: five health states representing levels of pruritus intensity over time (No, Mild, Moderate, Severe and Very severe CKD-aP), kidney transplant and death as the absorbing state. The model included patients with moderate to severe CKD-aP at baseline, in line with difelikefalin approved indication and clinical trials. Local costs, utilities, mortality rates and kidney transplant probabilities were obtained from published literature. Costs and quality-adjusted life-years (QALYs) were discounted at a 3% annual rate with a lifetime horizon (36 years). Results Difelikefalin was associated with an increased in QALYs (+0.49) and higher costs (+12,300€) compared to the BSC over a lifetime horizon. At a provisional cost estimate of 270.6€per 28-days for difelikefalin (based on a tentative list price for Spain), the incremental cost-utility ratio was 25,000€/QALY. The sensitivity analysis (DSA) confirmed the robustness of the results. The probabilistic sensitivity analysis (PSA), undertaken with 1000 iterations, indicated a 50% and 83% probability of difelikefalin being cost-effective at a willingness-to-pay (WTP) thresholds of 25,000 €/QALY and 30,000 €/QALY, respectively. Conclusions Difelikefalin could be a cost-effective option compared to BSC for the management of CKD-aP in adult haemodialysis patients within the Spanish NHS setting. Considering the unmet needs, these results support the convenience of incorporating difelikefalin in routine clinical practice in Spain.

Loss of keratinocyte differentiation is a leading cause in several skin diseases and needs to be controlled in adult homeostasis by for instance growth factors and proteases. Among them, we studied the role of isoform-rich dermokine - a wound- and tumour-related matrix metalloproteinase 10 substrate - via functional multi-omics. We generated dermokine isoform-dependent keratinocyte knockouts and three dimensional (3D) organotypic skin cultures and analyzed changes in their proteome and phosphoproteome by quantitative mass spectrometry. Through functional in vitro assays, we demonstrate that in the absence of dermokine-isoforms, p120 phosphorylation increases while cell-cell adhesion decreases in keratinocytes. Furthermore, we validate the link between decreased dermokine expression and phosphorylated p120-mediated adhesion in non-healing wounds samples derived from patients. Our data reveal a novel dermokine-p120-dependent cell-cell adhesion phenotype in keratinocytes and improve our understanding of wound-edge keratinocytes, expanding the hypothesis that dysregulated wounds resemble cancer.