Wirtschaftswissenschaftliche Beratung - Fluch oder Segen für die Politik?

Referat im Rahmen der Verabschiedung Herrn Prof. Dr. rer. pol. Günther Poser, gehalten am 14.07.2003 im Georg-Christoph-Lichtenberg Haus, Darmstadt.

Which attributes of whole genome sequencing tests are most important to the general population? Results from a German preference study

Objective: The aim of this study was to identify the preferences for whole genome sequencing (WGS) tests without genetic counseling. Methods: A discrete choice experiment was conducted where participants chose between two hypothetical alternatives consisting of the following attributes: test accuracy, test costs, identified diseases, probability of disease occurrence, and data access. People from the general German population aged ≥18 years were eligible to participate in the survey. We estimated generalized linear mixed effects models, latent class mixed-logit models, and the marginal willingness to pay. Results: Three hundred and one participants were included in the final analysis. Overall, the most favored WGS testing attributes were 95% test accuracy, report of severe hereditary diseases and 40% probability of disease development, test costs of €1,000, and access to test results for researchers. Subgroup analysis, however, showed differences in these preferences between males and females. For example, males preferred reporting of results at a 10% probability of disease development and females preferred reporting of results at a 40% probability. The test cost, participant’s educational level, and access to data influenced the willingness to participate in WGS testing in reality. Conclusion: The German general population was aware of the importance of genetic research and preferred to provide their own genetic data for researchers. However, among others, the reporting of results with a comparatively relatively low probability of disease development at a level of 40%, and the test accuracy of 95% had a high preference. This shows that the results and consequences of WGS testing without genetic counseling are hard to assess for individuals. Therefore, WGS testing should be supported by qualified genetic counseling, where the attributes and consequences are explained. © 2018 Plöthner et al

The Grey Zones of Classic Hodgkin Lymphoma

Simple Summary Classic Hodgkin lymphoma (CHL) is a well-defined lymphoid neoplasm with a minority of characteristic neoplastic cells of B cell origin, namely Hodgkin and Reed-Sternberg cells immersed in a rich reactive inflammatory infiltrate in the background. Although CHL has always been set apart from non-Hodgkin lymphomas, cases with morphological and phenotypic features intermediate between CHL and other lymphomas have been described. Whereas some of these lymphomas only represent morphological mimics, others exhibit mutational and gene expression profiles which overlap with CHL, indicating that these cases, frequently termed grey zone lymphomas, reside on the biological boundary between CHL and large B-cell lymphomas. In the present review, we aim to describe the current knowledge of these rare lymphomas, address diagnostic issues and summarize today's concepts on the classification of grey zone lymphomas and related tumors. Classic Hodgkin lymphoma (CHL) is a well-defined neoplasm characterized by the presence of a minority of pathognomonic Hodgkin and Reed-Sternberg (HRS) cells in a reactive inflammatory background. Although genotypically of B cell origin, HRS cells exhibit a downregulated B cell program and therefore are set apart from other B cell lymphomas in the current WHO classification. However, cases with morphological and phenotypic features overlapping with CHL have been recognized, and the category of B cell lymphoma-unclassifiable-with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL, also termed grey zone lymphoma, was first introduced into the WHO classification in 2008 as provisional entity. These cases, as well as others raising a differential diagnosis of CHL can present diagnostic problems, as well as therapeutic challenges. Whereas some of these lymphomas only represent biologically unrelated morphological mimics, others, especially mediastinal grey zone lymphoma, exhibit genetic and gene expression profiles which overlap with CHL, indicating a true biological relationship. In this review, we address areas of diagnostic difficulties between CHL and other lymphoma subtypes, discuss the biological basis of true grey zone lymphoma based on recent molecular studies and delineate current concepts for the classification of these rare tumors

Benefits of rIX-FP prophylaxis in patients with Haemophilia B: real-world evidence from a Spanish reference centre

Haemophilia B; pharmacokinetic; Real world evidenceHemofilia B; Farmacocinética; Evidencia del mundo realHemofília B; Farmacocinètica; Evidència del món realStandard FIX prophylaxis for PWHB require frequent injections, which has led to the development of extended half-life products like rIX-FP (albutrepenonacog alfa) that has shown good efficacy in clinical studies. This ambispective study aims to report a real-world experience with rIX-FP in a Spanish centre with PWHB who switched from SHL-FIX or began prophylaxis with rIX-FP. Five PWHB were included in this study, Four PTP switched to rIX-FP with prophylaxis every 7 days whilst one PUP started with an every-14-days regimen. 3 PTPs extended their dosing intervals to every 14 days or every 21 days. In all PTPs, median annualized spontaneous and joint bleeding rates were maintained at 0.00 and median (range) of ABR was 0.92 (0.00–2.77) after switch to rIX-FP. Mean trough level with previous product was 3.68% (SD = 2.06), while it was 7.08% (SD = 3) with all rIX-FP dosing intervals. After switching to rIX-FP, all PTP reduced their annual infusion rate between 50 and 84% and their annual FIX consumption by 61% (59–67%). This is the first reported real-world experience with albutrepenonacog alfa in a small cohort in Spain and demonstrates good bleeding control together with a reduction of the infusion rate, factor consumption and higher through factor level than previous treatment

Thrombospondin-3 augments injury-induced cardiomyopathy by intracellular integrin inhibition and sarcolemmal instability.

Thrombospondins (Thbs) are a family of five secreted matricellular glycoproteins in vertebrates that broadly affect cell-matrix interaction. While Thbs4 is known to protect striated muscle from disease by enhancing sarcolemmal stability through increased integrin and dystroglycan attachment complexes, here we show that Thbs3 antithetically promotes sarcolemmal destabilization by reducing integrin function, augmenting disease-induced decompensation. Deletion of Thbs3 in mice enhances integrin membrane expression and membrane stability, protecting the heart from disease stimuli. Transgene-mediated overexpression of α7β1D integrin in the heart ameliorates the disease predisposing effects of Thbs3 by augmenting sarcolemmal stability. Mechanistically, we show that mutating Thbs3 to contain the conserved RGD integrin binding domain normally found in Thbs4 and Thbs5 now rescues the defective expression of integrins on the sarcolemma. Thus, Thbs proteins mediate the intracellular processing of integrin plasma membrane attachment complexes to regulate the dynamics of cellular remodeling and membrane stability

A drug safety evaluation of abiraterone acetate in the treatment of prostate cancer

Introduction: To evaluate the safety profile characteristics of abiraterone acetate (AA) in the treatment of metastatic prostate cancer (mPCa). Areas covered: In this literature review the authors evaluate safety data from phase III trials investigating the combination of abiraterone acetate plus prednisone (AAP) in patients with metastatic prostate cancer. In particular, the aim was to clarify its toxicity profile, long-term exposure impact, and the correlation with general health-related quality of life (HRQoL). Expert opinion: Based on the studies reviewed, it appears that abiraterone acetate has favourable outcomes, is effective and well tolerated, mostly in asymptomatic or slightly symptomatic patients, and has recognised toxicity profile characteristics. Incidence of adverse events (AEs), such as mineralocorticoid- and corticosteroid-releated AEs, and hepatotoxicity is well known and widely described. Understanding the toxicity profile of AA could assist decision-making in clinical practice

Patient's adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: Is combination therapy better than monotherapy

Abstract BACKGROUND: Recent studies showed that the non-adherence to the pharmacological therapy of patients affected by BPH-associated LUTS increased the risk of clinical progression of BPH. We examined the patients adherence to pharmacological therapy and its clinical consequences in men with BPH-associated LUTS looking at the differences between drug classes comparing mono vs combination therapy. METHODS: A retrospective, population-based cohort study, using prescription administrative database and hospital discharge codes from a total of 1.5 million Italian men. Patients ≥ 40 years, administered alpha-blockers (AB) and 5alpha-reductase inhibitors (5ARIs), alone or in combination (CT), for BPH-associated LUTS were analyzed. The 1-year and long term adherence together with the analyses of hospitalization rates for BPH and BPH-related surgery were examined using multivariable Cox proportional hazards regression model and Pearson chi square test. RESULTS: Patients exposed to at least 6 months of therapy had a 1-year overall adherence of 29 % (monotherapy AB 35 %, monotherapy 5ARI 18 %, CT 9 %). Patient adherence progressively declined to 15 %, 8 % and 3 % for AB, 5ARI, and CT, respectively at the fifth year of follow up. Patients on CT had a higher discontinuation rate along all the follow-up compared to those under monotherapy with ABs or 5ARIs (all p < 0.0001). Moreover, CT was associated with a reduced risk of hospitalization for BPH-related surgery (HR 0.94; p < 0.0001) compared to AB monotherapy. CONCLUSIONS: Adherence to pharmacological therapy of BPH-associated LUTS is low and varies depending on drugs class. Patients under CT have a higher likelihood of discontinuing treatment for a number of reasons that should be better investigated. Our study suggests that new strategies aiming to increase patient's adherence to the prescribed treatment are necessary in order to prevent BPH progression

From genetics to therapy: Unraveling the complexities of Richter transformation in chronic lymphocytic leukemia

Chronic lymphocytic leukemia; Clonal evolution; Richter's transformationLeucèmia limfocítica crònica; Evolució clonal; Transformació de RichterLeucemia linfocítica crónica; Evolución clonal; Transformación de RichterRichter transformation (RT) refers to the progression of chronic lymphocytic leukemia, the most prevalent leukemia among adults, into a highly aggressive lymphoproliferative disorder, primarily a diffuse large B-cell lymphoma. This is a severe complication that continues to be a therapeutic challenge and remains an unmet medical need. Over the last five years, significant advances have occurred in uncovering the biological processes leading to the RT, refining criteria for properly diagnose RT from other entities, and exploring new therapeutic options beyond the ineffective chemotherapy. This review summarizes current knowledge in RT, including recent advances in the understanding of the pathogenesis of RT, in the classification of RT, and in the development of novel therapeutic strategies for this grave complication.This work was supported in part by the Instituto de Salud Carlos III, Fondo de Investigaciones Sanitarias [PI17/00943, F.B, PI18/01392, P.A.], and Gilead Fellowships, United States [GLD18/00047, F.B.] and Fundació la Marató de TV3, Spain [201905-30-31 F.B]. F.N. acknowledges research support from the American Association for Cancer Research (2021 AACR-Amgen Fellowship in Clinical/Translational Cancer Research, 21-40-11-NADE), the European Hematology Association (EHA Junior Research Grant 2021, RG-202012-00245), the Lady Tata Memorial Trust, India (International Award for Research in Leukaemia 2021–2022, LADY_TATA_21_3223)

Patient{'}s adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: Is combination therapy better than monotherapy

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