Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma (HD21): a randomised, multicentre, parallel, open-label, phase 3 trial.

BACKGROUND: Intensified systemic chemotherapy has the highest primary cure rate for advanced-stage, classical Hodgkin lymphoma but this comes with a cost of severe and potentially life long, persisting toxicities. With the new regimen of brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone (BrECADD), we aimed to improve the risk-to-benefit ratio of treatment of advanced-stage, classical Hodgkin lymphoma guided by PET after two cycles. METHODS: This randomised, multicentre, parallel, open-label, phase 3 trial was done in 233 trial sites across nine countries. Eligible patients were adults (aged ≤60 years) with newly diagnosed, advanced-stage, classical Hodgkin lymphoma (ie, Ann Arbor stage III/IV, stage II with B symptoms, and either one or both risk factors of large mediastinal mass and extranodal lesions). Patients were randomly assigned (1:1) to four or six cycles (21-day intervals) of escalated doses of etoposide (200 mg/m2 intravenously on days 1-3), doxorubicin (35 mg/m2 intravenously on day 1), and cyclophosphamide (1250 mg/m2 intravenously on day 1), and standard doses of bleomycin (10 mg/m2 intravenously on day 8), vincristine (1·4 mg/m2 intravenously on day 8), procarbazine (100 mg/m2 orally on days 1-7), and prednisone (40 mg/m2 orally on days 1-14; eBEACOPP) or BrECADD, guided by PET after two cycles. Patients and investigators were not masked to treatment assignment. Hierarchical coprimary objectives were to show (1) improved tolerability defined by treatment-related morbidity and (2) non-inferior efficacy defined by progression-free survival with an absolute non-inferiority margin of 6 percentage points of BrECADD compared with eBEACOPP. An additional test of superiority of progression-free survival was to be done if non-inferiority had been established. Analyses were done by intention to treat; the treatment-related morbidity assessment required documentation of at least one chemotherapy cycle. This trial was registered at ClinicalTrials.gov (NCT02661503). FINDINGS: Between July 22, 2016, and Aug 27, 2020, 1500 patients were enrolled, of whom 749 were randomly assigned to BrECADD and 751 to eBEACOPP. 1482 patients were included in the intention-to-treat analysis. The median age of patients was 31 years (IQR 24-42). 838 (56%) of 1482 patients were male and 644 (44%) were female. Most patients were White (1352 [91%] of 1482). Treatment-related morbidity was significantly lower with BrECADD (312 [42%] of 738 patients) than with eBEACOPP (430 [59%] of 732 patients; relative risk 0·72 [95% CI 0·65-0·80]; p<0·0001). At a median follow-up of 48 months, BrECADD improved progression-free survival with a hazard ratio of 0·66 (0·45-0·97; p=0·035); 4-year progression-free survival estimates were 94·3% (95% CI 92·6-96·1) for BrECADD and 90·9% (88·7-93·1) for eBEACOPP. 4-year overall survival rates were 98·6% (97·7-99·5) and 98·2% (97·2-99·3), respectively. INTERPRETATION: BrECADD guided by PET after two cycles is better tolerated and more effective than eBEACOPP in first-line treatment of adult patients with advanced-stage, classical Hodgkin lymphoma. FUNDING: Takeda Oncology.

[DNVF Memorandum Health Literacy (Part 2) - Operationalisation and Measuring of Health Literacy from a Health Services Research Perspective]. / DNVF Memorandum Gesundheitskompetenz (Teil II) ­ Operationalisierung und Messung von Gesundheitskompetenz aus Sicht der Versorgungsforschung.

The "DNVF Memorandum Health Literacy (Part 2): Operationalization and Measurement of Health Literacy from the Perspective of Health Services Research" of the German Network for Health Services Research represents the continuation of the memorandum "DNVF Memorandum Health Literacy (Part 1): Background, Subject and Issues in Health Services Research". In addition to the general requirements for the measurement of health literacy, this memorandum also deals with the specific requirements, such as the differentiation of health literacy from related constructs, the differences between performance-based and self-assessment methods, the differences between generic and specific instruments, the use of screening instruments, and the measurement of health literacy in special populations. Furthermore, special considerations about the measurement of digital health literacy, potentials of qualitative and participatory research approaches as well as research ethics in the measurement of health literacy will be elaborated on. A special emphasis is placed on practical relevance for health services researchers. Finally, the authors will give an outlook on challenges and research desiderata in connection with the measurement of health literacy in the context of health services research.

Employees Receiving Inpatient Treatment for Common Mental Disorders in Germany: Factors Associated with Time to First and Full Return to Work.

Purpose In Germany, return to work (RTW) after inpatient treatment for common mental disorders (CMDs) is a complex process at the intersection of the mental healthcare system and the workplace. This study examined (1) the time to first and full RTW and (2) associated factors among employees receiving inpatient treatment for CMDs. Methods In this prospective cohort study, employees receiving inpatient psychiatric or medical rehabilitation treatment for CMDs were interviewed by phone during their last week before discharge. Follow-up interviews were conducted after 6, 12, and 18 months. Health-, personal, and work-related factors were used from baseline measurement. Parametric survival analysis was conducted to identify factors associated with time to first and full RTW. Results A total of N = 269 participants who stayed at a psychiatric clinic or a medical rehabilitation facility were included. Almost all participants (n = 252, 94%) from both treatment settings reported a first RTW and a full RTW. The time to first and full RTW was shortest among participants from medical rehabilitation (both median 6 days) and longer among participants from psychiatric treatment (median 17 days to first RTW and 73 days to full RTW). While only health-related and personal factors were associated with time to first RTW, leadership quality and needed individual RTW support were associated with time to full RTW. Conclusions More attention to work accommodation needs for RTW in clinical practice and coordinated actions towards RTW in collaboration with key RTW stakeholders in the workplace may support a timely RTW.Clinical Registration Number DRKS00010903, retrospectively registered.

Returning to work after sickness absence due to common mental disorders: study design and baseline findings from an 18 months mixed methods follow-up study in Germany.

BACKGROUND: With nearly 30 % of the general population experiencing one mental disorder in 12 months, common mental disorders (CMDs) are highly prevalent in Germany and mainly affect the workforce. Therefore, the processes of successfully returning to work (RTW) and achieving a sustainable RTW (SRTW) are important not only for recovery but the prevention of negative consequences like job loss or disability retirement. While factors influencing and predicting the time until RTW are well-investigated in other countries, research on determinants of RTW and SRTW has received little attention in Germany. Consequently, this study aims to investigate the RTW and SRTW processes due to CMDs from the employees´ perspective in Germany. METHODS: This prospective cohort study uses a convergent parallel mixed methods design with a quantitative sample and qualitative sub-sample. Two hundred eighty-six participants of the quantitative study and a sub-sample of 32 participants of the qualitative study were included. The primary outcome of the quantitative study is the time until RTW and full RTW. The secondary outcome is the sustainability of RTW. The following measures will be used to cover work-, RTW- and health-related factors: working time, duration of sickness absences, functional ability, work ability, RTW self-efficacy, social support, work-privacy conflict, job satisfaction, job crafting and depressive symptoms. Quantitative and qualitative data will be integrated at the end. DISCUSSION: The paper provides an overview on study design, recruitment, sample characteristics and baseline findings of an 18 months mixed methods follow-up study in Germany. This study will provide evidence of (S)RTW processes and its influencing factors due to CMDs in Germany and therefore contribute to further improvement of its (S)RTW practices. TRIAL REGISTRATION: German Clinical Trials Register (ID: DRKS00010903, July 28, 2017, retrospectively registered).