A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis

BACKGROUND: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin. METHODS: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course. DISCUSSION: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages. TRIAL REGISTRATION: DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832)

Preparing Institutions to Implement Harmonized Medicine and Nursing Curricula Through the Use of Cross-Institutional Faculty Developers

Doreen Anna Mloka,1 Francis Sakita,2 Irene Kida Minja,3 Haruna Dika,4 Edith AM Tarimo,5 Nathanael Sirili,6 Lillian Teddy Mselle,7 Rodrick Richard Kisenge,8 Philip Sasi,9 Livuka Nsemwa,10 Delfina R Msanga,11 Einoti Yohana Matayan,12 Nicholaus Bartholomeo Ngowi,13 Mainen Julius Moshi,14 John Bartlett,15 Sarah B Macfarlane,16 Ephata Kaaya,17 Patricia S O’Sullivan18 1Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 2Department of Emergency Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 3Department of Restorative Dentistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 4Department of Anatomy, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 5Department of Nursing Management, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 6Department of Development Studies, Muhimbili University of Health and Allied Sciences, School of Public Health and Social Sciences, Dar es Salaam, Tanzania; 7Department of Clinical Nursing, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 8Department of Pediatrics and Child Health, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 9Department of Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 10Department of Nursing and Midwifery, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 11Department of Pediatrics and Child Health, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 12Department of Ophthalmology, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 13Department of Surgery, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 14Department of Biological and Preclinical Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 15Department of Global Health and Medicine, Duke University, Durham, NC, USA; 16Department of Global Health Sciences, University of San Francisco California, San Francisco, CA, USA; 17Department of Pathology, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 18Office of Research and Development in Medical Education, University of San Francisco California, San Francisco, CA, USACorrespondence: Doreen Anna Mloka, Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, 9 United Nations Road, P.O. Box 650013, Dar es Salaam, Tanzania, Tel +255712459528, Email [email protected]: Effective implementation of new curricula requires faculty to be knowledgeable about curriculum goals and have the appropriate pedagogical skills to implement the curriculum, even more so if the new curriculum is being deployed at multiple institutions. In this paper, we describe the process of creating a common faculty development program to train cross-institutional faculty developers to support the implementation of national harmonized medicine and nursing curricula.Methods: A five-step approach was used, including a cross-institutional needs assessment survey for faculty development needs, the development of a generic faculty development program, the identification and training of cross-institutional faculty educators, and the implementation of cross-institutional faculty capacity-building workshops.Results: A list of common cross-cutting faculty development needs for teaching and learning was identified from the needs assessment survey and used to develop an accredited, cross-institutional faculty development program for competency-based learning and assessment. A total of 24 cross-institutional faculty developers were identified and trained in 8 core learning and assessment workshops. A total of 18 cross-institutional and 71 institutional workshops were conducted, of which 1292 faculty members and 412 residents were trained, and three cross-institutional educational research projects were implemented.Conclusion: The success attained in this study shows that the use of cross-institutional faculty developers is a viable model and sustainable resource that can be used to support the implementation of harmonized national curricula.Keywords: faculty development across institution

Burden and associated phenotypic characteristics of tuberculosis infection in adult Africans with diabetes: a systematic review.

Diabetes mellitus (DM) increases the risk of developing tuberculosis infection (TBI). However, the evidence on the burden and phenotypic characteristics of TBI in African patients with DM is limited. This study aimed to determine the prevalence and characterisation of TBI in native African patients living with DM. We searched PubMed, EMBASE, and African Journals Online for original studies reporting information on the prevalence and characteristics of TBI in adult Africans with DM. A forest plot was used to describe the pooled prevalence estimate of TBI and the corresponding 95% confidence intervals (CI). Six studies conducted in four African countries involving 721 participants with DM were included in this systematic review. The pooled prevalence estimate of TBI was 40% (95% CI 20-60%, I2 = 98.52%, p < 0.001). Age ≥ 40 years and glycated haemoglobin levels independently predicted TBI positivity in patients with DM in three studies. Africans with DM have a high prevalence of TBI, especially those who are older or with poorly controlled diabetes. This justifies the need for studies to explore how to screen and manage TBI to avert the progression to active TB disease