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Abstract Background Many patients with allergic rhinitis (AR) have moderate-to-severe persistent AR. Meda Pharma’s AzeFlu (MP-AzeFlu ® ) is an intranasal AR treatment comprising a novel formulation of azelastine hydrochloride and fluticasone propionate in a single device. Methods This prospective observational study of 214 adults and adolescents in Austria with moderate-to-severe persistent AR assessed the effectiveness of MP-AzeFlu (one spray/nostril twice daily; daily doses: azelastine hydrochloride 548 μg; and fluticasone propionate 200 μg) for AR control in clinical practice using the visual analog scale. Symptom severity was reported on days 0, 1, 3, 7, 14, 21, 28, 35, and 42. Patient demographics, AR phenotype, allergen sensitization, symptomatology, AR treatments in the previous year, and the reason for the MP-AzeFlu prescription were recorded. Results MP-AzeFlu treatment was associated with a rapid and statistically significant reduction in the visual analog scale score from baseline to each timepoint measured, including day 1 (all p

Abstract Dupilumab is a monoclonal antibody against the IL‐4 receptor alpha which has shown efficacy in T2 high severe asthmatics in phase 3 randomized controlled trials. The purpose of this real‐life study is to demonstrate the real‐life effectiveness of dupilumab in Austrian severe asthma patients. We retrospectively analyzed all patients receiving dupilumab at our severe asthma clinic. Thirteen patients have so far received dupilumab at our center. The primary outcome, asthma control questionnaire 6‐item scale at 2 weeks, improved by 0.57 points (p = .014), which is statistically and clinically significant. Similarly, the asthma control test at 4 weeks improved by 3.91 points (p = .024), also statistically and clinically significant. Improvements in forced expiratory volume in 1 s at 2 weeks were neither statistically, nor clinically significant. Improvements at 4 weeks (+220 ml, p = .041), and 3 months (+229 ml, p = .006), were statistically significant and clinically borderline significant. No severe adverse events or hypereosinophilia were observed. No adverse events led to treatment discontinuation. Most patients (85%) had previously received monoclonal antibody treatment for severe asthma. Previous monoclonal antibody treatment had been discontinued in these patients due to a lack of clinical response. Dupilumab is effective and safe in Austrian real‐life severe asthmatics. It provides a possible treatment strategy for T2 high severe asthmatics who do not qualify for anti‐immunoglobulin E or anti‐IL5/IL5R monoclonal antibody treatments or do not adequately respond to these.

Objective: Scant clinical data are available on the effects of current treatments for asthma on different subgroups of patients with this disease. We conducted a prospective, noninterventional, multicenter real-life study in adult patients with persistent asthma, and we specifically analyzed the effects of treatment with extrafine beclometasone dipropionate/formoterol (BDP/F) in asthma patients categorized by phenotypes related to small airways (i.e. smoking habits, disease duration, and air trapping). Methods: Patients received BDP/F as a fixed combination (100/6 μg), administered in 1–2 inhalations twice daily over a period of 12 weeks. Peak expiratory flow (PEF), forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), number of asthma attacks, asthma control, and severity of asthma symptoms were evaluated in the overall population and in different subgroups at three different time points. Results: Overall, 213 patients were enrolled. In the overall population the treatment resulted in a significant increase in the proportion of well controlled patients (from 6.1% to 66.3%; p

The infection of CD4+ cells by HIV leads to the progressive destruction of CD4+ T lymphocytes and, after a severe reduction of CD4+ cells, to AIDS. The aim of the study was to investigate whether HIV-infected patients with CD4 cell counts

The phosphoinositide 3-kinase (PI3-kinase) and the mammalian target of rapamycin (mTOR) are two major signaling molecules involved in growth and activation of mast cells (MC) and basophils (BA). We examined the effects of the dual PI3-kinase/mTOR blocker NVP-BEZ235 on growth of normal and neoplastic BA and MC as well as immunoglobulin E (IgE)-dependent cell activation. Growth of MC and BA were determined by measuring (3)H-thymidine uptake and apoptosis. Cell activation was determined in histamine release experiments and by measuring upregulation of CD63 and CD203c after challenging with IgE plus anti-IgE or allergen. We found that NVP-BEZ235 exerts profound inhibitory effects on growth of primary and cloned neoplastic MC. In the MC leukemia cell line HMC-1, NVP-BEZ235 showed similar IC(50) values in the HMC-1.1 subclone lacking KIT D816V (0.025 µM) and the HMC-1.2 subclone expressing KIT D816V (0.005 µM). Moreover, NVP-BEZ235 was found to exert strong growth-inhibitory effects on neoplastic MC in a xenotransplant-mouse model employing NMR1-Foxn1(nu) mice. NVP-BEZ235 also exerted inhibitory effects on cytokine-dependent differentiation of normal BA and MC, but did not induce growth inhibition or apoptosis in mature MC or normal bone marrow cells. Finally, NVP-BEZ235 was found to inhibit IgE-dependent histamine release in BA and MC (IC(50) 0.5-1 µM) as well as anti-IgE-induced upregulation of CD203c in BA and IgE-dependent upregulation of CD63 in MC. In summary, NVP-BEZ235 produces growth-inhibitory effects in immature neoplastic MC and inhibits IgE-dependent activation of mature BA and MC. Whether these potentially beneficial drug effects have clinical implications is currently under investigation.

The coronavirus disease 2019 (COVID-19) pandemic challenged many national health care systems, with hospitals reaching capacity limits of intensive care units (ICU). Thus, the estimation of acute local burden of ICUs is critical for appropriate management of health care resources. In this work, we applied non-linear mixed effects modeling to develop an epidemiological SARS-CoV-2 infection model for Germany, with its 16 federal states and 400 districts, that describes infections as well as COVID-19 inpatients, ICU patients with and without mechanical ventilation, recoveries, and fatalities during the first two waves of the pandemic until April 2021. Based on model analyses, covariates influencing the relation between infections and outcomes were explored. Non-pharmaceutical interventions imposed by governments were found to have a major impact on the spreading of SARS-CoV-2. Patient age and sex, the spread of variant B.1.1.7, and the testing strategy (number of tests performed weekly, rate of positive tests) affected the severity and outcome of recorded cases and could reduce the observed unexplained variability between the states. Modeling could reasonably link the discrepancies between fine-grained model simulations of the 400 German districts and the reported number of available ICU beds to coarse-grained COVID-19 patient distribution patterns within German regions.