Assessing the health-related management of people with differences of sex development

Purpose Health care requirements and perception of people with differences of sex development (DSD) have changed enormously since the "Chicago Consensus Conference" in 2005. Therefore, new standards of care and evaluation of care have to be developed. Methods We summarize the social and legal approach to care for DSD during the last two decades and report the main results of European research activities. Results The last two decades were accompanied by legal and societal discussion regarding how to deal with a nonbinary concept of sex. This leads to the necessity to assess health care requirements for individuals with DSD in an objective manner. We briefly review the results of the recently funded European research projects dealing with health-related issues in DSD like EU COST Action DSD, I-DSD, and dsd-LIFE, and address the compilation of quality indicators that will be needed to benchmark health care provision and health care-related outcomes. Conclusions The benchmarking process has to be implemented among health care providers for individuals with DSD within the European Reference Networks for Rare Conditions

Venetoclax enhances the efficacy of therapeutic antibodies in B-cell malignancies by augmenting tumor cell phagocytosis

Immunotherapy has evolved as a powerful tool for the treatment of B-cell malignancies, and patient outcomes have improved by combining therapeutic antibodies with conventional chemotherapy. Overexpression of antiapoptotic B-cell lymphoma 2 (Bcl-2) is associated with a poor prognosis, and increased levels have been described in patients with "double-hit" diffuse large B-cell lymphoma, a subgroup of Burkitt's lymphoma, and patients with pediatric acute lymphoblastic leukemia harboring a t(17;19) translocation. Here, we show that the addition of venetoclax (VEN), a specific Bcl-2 inhibitor, potently enhanced the efficacy of the therapeutic anti-CD20 antibody rituximab, anti-CD38 daratumumab, and anti-CD19-DE, a proprietary version of tafasitamab. This was because of an increase in antibody-dependent cellular phagocytosis by macrophages as shown in vitro and in vivo in cell lines and patient-derived xenograft models. Mechanistically, double-hit lymphoma cells subjected to VEN triggered phagocytosis in an apoptosis-independent manner. Our study identifies the combination of VEN and therapeutic antibodies as a promising novel strategy for the treatment of B-cell malignancies

Cardiac Resynchronisation Therapy in Patients with Moderate to Severe Heart Failure in Germany: A Cost-Utility Analysis of the Additional Defibrillator

Background!#!Cardiac resynchronisation therapy (CRT) is a well-established form of treatment for patients with heart failure and cardiac dyssynchrony. There are two different types of CRT devices: the biventricular pacemaker (CRT-P) and the biventricular defibrillator (CRT-D). The latter is more complex but also more expensive. For the majority of patients who are eligible for CRT, both devices are appropriate according to current guidelines. The purpose of this study was to conduct a cost-utility analysis for CRT-D compared to CRT-P from a German payer's perspective.!##!Methods!#!A cohort Markov-model was developed to assess average costs and quality-adjusted life-years (QALY) for CRT-D and CRT-P. The model consisted of six stages: one for the device implementation, one for the absorbing state death, and two stages ('Stable' and 'Hospital') for either a CRT device or medical therapy. The time horizon was 20 years. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted.!##!Results!#!The incremental cost-effectiveness ratio (ICER) of CRT-D compared with CRT-P was €24,659 per additional QALY gained. In deterministic sensitivity analysis, the survival advantage of CRT-D to CRT-P was the most influential input parameter. In the probabilistic sensitivity analysis 96% of the simulated cases were more effective but also more costly.!##!Conclusions!#!Therapy with CRT-D compared to CRT-P resulted in an additional gain of QALYs, but was more expensive. In addition, the ICER was subject to uncertainty, especially due to the uncertainty in the survival benefit. A randomised controlled trial and subgroup analyses would be desirable to further inform decision making

Survival of patients undergoing cardiac resynchronization therapy with or without defibrillator: the RESET-CRT project

AIMS: Cardiac resynchronization therapy (CRT) is an established treatment for heart failure. There is contradictory evidence whether defibrillator capability improves prognosis in patients receiving CRT. We compared the survival of patients undergoing de novo implantation of a CRT with defibrillator (CRT-D) option and CRT with pacemaker (CRT-P) in a large health claims database. METHODS AND RESULTS: Using health claims data of a major German statutory health insurance, we analysed patients with de novo CRT implantation from 2014 to 2019 without indication for defibrillator implantation for secondary prevention of sudden cardiac death. We performed age-adjusted Cox proportional hazard regression and entropy balancing to calculate weights to control for baseline imbalances. The analysis comprised 847 CRT-P and 2722 CRT-D patients. Overall, 714 deaths were recorded during a median follow-up of 2.35 years. A higher cumulative incidence of all-cause death was observed in the initial unadjusted Kaplan-Meier time-to-event analysis [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.38-1.92]. After adjustment for age, HR was 1.13 (95% CI: 0.95-1.35) and after entropy balancing 0.99 (95% CI: 0.81-1.20). No survival differences were found in different age groups. The results were robust in sensitivity analyses. CONCLUSION: In a large health claims database of CRT implantations performed in a contemporary setting, CRT-P treatment was not associated with inferior survival compared with CRT-D. Age differences accounted for the greatest part of the survival difference that was observed in the initial unadjusted analysis