Search

Background: Patients with end-stage kidney disease require complex and expensive medical management. Kidney transplantation remains the treatment of choice for end-stage kidney disease and is considered superior to all other modalities of renal replacement therapy or dialysis. However, access to kidney transplant is limited by critical supply and demand, making it extremely important to ensure longevity of transplanted kidneys. This is prevented through lifelong immunosuppression, with caution not to overly suppress the immune system, resulting in toxicity and harm. Transition of care to community nephrologists after initial kidney transplantation and monitoring at a transplant center is an important process to ensure delivery of effective and patient-centric care closer to home. Once transplanted, laborious surveillance of the immune system and monitoring for potential rejection and injury are undertaken through an armamentarium of screening modalities. Posttransplant surveillance for kidney function and injury remains key to follow-up care. While kidney function, quantified by estimated glomerular filtration rate and serum creatinine, and kidney injury, measured by proteinuria and hematuria, are standard biomarkers used to monitor injury and rejection posttransplant, they have recently been demonstrated to be inferior in performance to that of AlloSure (CareDx Inc, Brisbane, CA) circulating donor-derived, cell-free DNA (dd-cfDNA)., Objective: The outcomes and methods of monitoring renal transplant recipients posttransplant have remained stagnant over the past 15 years. The aim of this study is to consider intensive surveillance using AlloSure dd-cfDNA in an actively managed protocol, assessing whether it increases long-term allograft survival in kidney transplant recipients compared with current standard clinical care in community nephrology., Methods: The study protocol will acquire data from a phase IV observational trial to assess a cohort of renal transplant patients managed using AlloSure dd-cfDNA and patient care managers versus 1000 propensity-matched historic controls using United Network for Organ Sharing U.S. Scientific Registry of Transplant Recipients data. Data will be managed in a centralized electronic data server. The primary outcome will be superior allograft survival, as a composite of return to dialysis, retransplant, death due to allograft failure, and death with a functional graft (infection, malignancy, and cardiovascular death). The secondary endpoints will assess improved kidney function through decline in estimated glomerular filtration rate and immune activity through development of donor-specific antibodies., Results: The total sample is anticipated to be 3500 (2500 patients managed with AlloSure dd-cfDNA and 1000 propensity-matched controls). Active enrollment began in November 2020., Conclusions: Based on a significant literature base, we believe implementing the surveillance of dd-cfDNA in the kidney transplant population will have a positive impact on graft survival. Through early identification of rejection and facilitating timely intervention, prolongation of allograft survival versus those not managed by dd-cfDNA surveillance protocol should be superior., International Registered Report Identifier (irrid): PRR1-10.2196/25941., (©Bethany L Dale, Subhasish Bose, Sheng Kuo, Alana Burns, Pierre Daou, Jenna Short, Jake Miles. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.03.2021.)

Background: Interventions to reduce child deaths in Africa have often underachieved, causing the Millennium Development Goal targets to be missed. We assessed whether a community enquiry into the circumstances of death could improve intervention effectiveness by identifying local avoidable factors and explaining implementation failures., Methods: Deaths of children younger than 5 years were ascertained by community informants in two districts in Mali (762 deaths) and three districts in Uganda (442 deaths) in 2011-15. Deaths were investigated by interviewing parents and health workers. Investigation findings were reviewed by a panel of local health-care workers and community representatives, who formulated recommendations to address avoidable factors and, subsequently, oversaw their implementation., Findings: At least one avoidable factor was identified in 97% (95% CI 96-98, 737 of 756) of deaths in children younger than 5 years in Mali and 95% (93-97, 389 of 409) in Uganda. Suboptimal newborn care was a factor in 76% (146 of 194) of neonatal deaths in Mali and 64% (134 of 194) in Uganda. The most frequent avoidable factor in postneonatal deaths was inadequate child protection (mainly child neglect) in Uganda (29%, 63 of 215) and malnutrition in Mali (22%, 124 of 562). 84% (618 of 736 in Mali, 328 of 391 in Uganda) of families had consulted a health-care provider for the fatal illness, but the quality of care was often inadequate. Even in official primary care clinics, danger signs were often missed (43% of cases in Mali [135 of 396], 39% in Uganda [30 of 78]), essential treatment was not given (39% in Mali [154 of 396], 35% in Uganda [27 of 78]), and patients who were seriously ill were not referred to a hospital in time (51% in Mali [202 of 396], 45% in Uganda [35 of 78]). Local recommendations focused on quality of care in health-care facilities and on community issues influencing treatment-seeking behaviour., Interpretation: Local investigation and review of circumstances of death of children in sub-Saharan Africa is likely to lead to more effective interventions than simple consideration of the biomedical causes of death. This approach discerned local public health priorities and implementable solutions to address the avoidable factors identified., Funding: European Union's 7th Framework Programme for research and technological development., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The World Health Organization defines a "critical shortage" of health workers as being fewer than 2.28 health workers per 1000 population and failing to attain 80% coverage for deliveries by skilled birth attendants. We aimed to quantify the number of health workers in five African countries and the proportion of these currently working in primary health care facilities, to compare this to estimates of numbers needed and to assess how the situation has changed in recent years., Methods: This study is a review of published and unpublished "grey" literature on human resources for health in five disparate countries: Mali, Sudan, Uganda, Botswana and South Africa., Results: Health worker density has increased steadily since 2000 in South Africa and Botswana which already meet WHO targets but has not significantly increased since 2004 in Sudan, Mali and Uganda which have a critical shortage of health workers. In all five countries, a minority of doctors, nurses and midwives are working in primary health care, and shortages of qualified staff are greatest in rural areas. In Uganda, shortages are greater in primary health care settings than at higher levels. In Mali, few community health centres have a midwife or a doctor. Even South Africa has a shortage of doctors in primary health care in poorer districts. Although most countries recognize village health workers, traditional healers and traditional birth attendants, there are insufficient data on their numbers., Conclusion: There is an "inverse primary health care law" in the countries studied: staffing is inversely related to poverty and level of need, and health worker density is not increasing in the lowest income countries. Unless there is money to recruit and retain staff in these areas, training programmes will not improve health worker density because the trained staff will simply leave to work elsewhere. Information systems need to be improved in a way that informs policy on the health workforce. It may be possible to use existing resources more cost-effectively by involving skilled staff to supervise and support lower level health care workers who currently provide the front line of primary health care in most of Africa.

Context: Steroid 5α-reductase inhibitors are used to treat benign prostatic hyperplasia and androgenic alopecia, but the role of 5α-dihydrotestosterone (DHT) in mediating testosterone's effects on muscle, sexual function, erythropoiesis, and other androgen-dependent processes remains poorly understood., Objective: To determine whether testosterone's effects on muscle mass, strength, sexual function, hematocrit level, prostate volume, sebum production, and lipid levels are attenuated when its conversion to DHT is blocked by dutasteride (an inhibitor of 5α-reductase type 1 and 2)., Design, Setting, and Patients: The 5α-Reductase Trial was a randomized controlled trial of healthy men aged 18 to 50 years comparing placebo plus testosterone enthanate with dutasteride plus testosterone enanthate from May 2005 through June 2010., Interventions: Eight treatment groups received 50, 125, 300, or 600 mg/wk of testosterone enanthate for 20 weeks plus placebo (4 groups) or 2.5 mg/d of dutasteride (4 groups)., Main Outcome Measures: The primary outcome was change in fat-free mass; secondary outcomes: changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels., Results: A total of 139 men were randomized; 102 completed the 20-week intervention. Men assigned to dutasteride were similar at baseline to those assigned to placebo. The mean fat-free mass gained by the dutasteride groups was 0.6 kg (95% CI, -0.1 to 1.2 kg) when receiving 50 mg/wk of testosterone enanthate, 2.6 kg (95% CI, 0.9 to 4.3 kg) for 125 mg/wk, 5.8 kg (95% CI, 4.8 to 6.9 kg) for 300 mg/wk, and 7.1 kg (95% CI, 6.0 to 8.2 kg) for 600 mg/wk. The mean fat-free mass gained by the placebo groups was 0.8 kg (95% CI, -0.1 to 1.7 kg) when receiving 50 mg/wk of testosterone enanthate, 3.5 kg (95% CI, 2.1 to 4.8 kg) for 125 mg/wk, 5.7 kg (95% CI, 4.8 to 6.5 kg) for 300 mg/wk, and 8.1 kg (95% CI, 6.7 to 9.5 kg) for 600 mg/wk. The dose-adjusted differences between the dutasteride and placebo groups for fat-free mass were not significant (P = .18). Changes in fat mass, muscle strength, sexual function, prostate volume, sebum production, and hematocrit and lipid levels did not differ between groups., Conclusion: Changes in fat-free mass in response to graded testosterone doses did not differ in men in whom DHT was suppressed by dutasteride from those treated with placebo, indicating that conversion of testosterone to DHT is not essential for mediating its anabolic effects on muscle., Trial Registration: clinicaltrials.gov Identifier: NCT00493987.