Estimates of aid for reproductive, maternal, newborn, and child health: findings from application of the Muskoka2 method, 2002-17.

BACKGROUND: Four methods have previously been used to track aid for reproductive, maternal, newborn, and child health (RMNCH). At a meeting of donors and stakeholders in May, 2018, a single, agreed method was requested to produce accurate, predictable, transparent, and up-to-date estimates that could be used for analyses from both donor and recipient perspectives. Muskoka2 was developed to meet these needs. We describe Muskoka2 and present estimates of levels and trends in aid for RMNCH in 2002-17, with a focus on the latest estimates for 2017. METHODS: Muskoka2 is an automated algorithm that generates disaggregated estimates of aid for reproductive health, maternal and newborn health, and child health at the global, donor, and recipient-country levels. We applied Muskoka2 to the Organisation for Economic Co-operation and Development's Creditor Reporting System (CRS) aid activities database to generate estimates of RMNCH disbursements in 2002-17. The percentage of disbursements that benefit RMNCH was determined using CRS purpose codes for all donors except Gavi, the Vaccine Alliance; the UN Population Fund; and UNICEF; for which fixed percentages of aid were considered to benefit RMNCH. We analysed funding by donor for the 20 largest donors, by recipient-country income group, and by recipient for the 16 countries with the greatest RMNCH need, defined as the countries with the worst levels in 2015 on each of seven health indicators. FINDINGS: After 3 years of stagnation, reported aid for RMNCH reached $15·9 billion in 2017, the highest amount ever reported. Among donors reporting in both 2016 and 2017, aid increased by 10$1·4 billion) to $15·4 billion between 2016 and 2017. Child health received almost half of RMNCH disbursements in 2017 (46$7·4 billion), followed by reproductive health (34%, $5·4 billion), and maternal and newborn health (19$3·1 billion). The USA ($5·8 billion) and the UK ($1·6 billion) were the largest bilateral donors, disbursing 46% of all RMNCH funding in 2017 (including shares of their core contributions to multilaterals). The Global Fund and Gavi were the largest multilateral donors, disbursing $1·7 billion and$1·5 billion, respectively, for RMNCH from their core budgets. The proportion of aid for RMNCH received by low-income countries increased from 31% in 2002 to 52% in 2017. Nigeria received 7% ($1·1 billion) of all aid for RMNCH in 2017, followed by Ethiopia (6$876 million), Kenya (5%, $754 million), and Tanzania (5$751 million). INTERPRETATION: Muskoka2 retains the speed, transparency, and donor buy-in of the G8's previous Muskoka approach and incorporates eight innovations to improve precision. Although aid for RMNCH increased in 2017, low-income and middle-income countries still experience substantial funding gaps and threats to future funding. Maternal and newborn health receives considerably less funding than reproductive health or child health, which is a persistent issue requiring urgent attention. FUNDING: Bill & Melinda Gates Foundation; Partnership for Maternal, Newborn & Child Health

Cortisol awakening response over the course of humanitarian aid deployment: A prospective cohort study

Alastair Ager - ORCID 0000-0002-9474-3563 https://orcid.org/0000-0002-9474-3563Added VoR 2021-01-05Background: Internationally deployed humanitarian aid (HA) workers are routinely confronted with potentially traumatic stressors. However, it remains unknown whether HA deployment and related traumatic stress are associated with long-term changes in hypothalamic-pituitary-adrenal (HPA) axis function. Therefore, we investigated whether cortisol awakening response (CAR) decreased upon deployment and whether this was moderated by previous and recent trauma exposure and parallel changes in symptom severity and perceived social support.Methods: In this prospective study, n=86 HA workers (68% females) completed questionnaires regarding trauma exposure, posttraumatic stress disorder (PTSD), anxiety and depressive symptoms and perceived social support, as well as salivary cortisol assessments at awakening and 30 minutes post-awakening at before, early and 3-6 months post-deployment.Results: Linear mixed models showed significantly decreased CAR (b(SE)=-.036(.011), p=.002) and awakening cortisol over time (b(SE)=-.007(.003), p=.014). The extent of awakening cortisol change was significantly moderated by interactions between previous and recent trauma exposure. Also, a steeper awakening cortisol decrease was significantly associated with higher mean anxiety and PTSD symptoms across assessments. No significant effects were found for social support.Conclusions: We observed attenuated CAR and awakening cortisol upon HA deployment, with a dose-response effect between trauma exposure before and during the recent deployment on awakening cortisol. Awakening cortisol change was associated with PTSD and anxiety symptom levels across assessments. Our findings support the need for organizational awareness that work-related exposures may have long-lasting biological effects. Further research assessing symptoms and biological measures in parallel is needed to translate current findings into guidelines on the individual level.This work was funded by the US Centers for Disease Control and Prevention and the Antares Foundation through a cooperative agreement [Grant Number: 5U01EH000217]; The first author Yulan Qing is financially supported by the Chinese Scholarship Council Grant for her Ph.D. (NO. 201504910771). Additionally, Mirjam van Zuiden was supported by a Veni grant from the Netherlands organization for Health research and Development (ZonMw, grant no. 91617037). The funding source had no role in the design or execution of the research.https://doi.org/10.1080/20008198.2020.181664911pubpub

Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background: Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings: LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). Conclusions: LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP

Costing Human Rights and Community Support Interventions as a Part of Universal Access to HIV Treatment and Care in a Southern African Setting

Expanding access to antiretroviral therapy (ART) has both individual health benefits and potential to decrease HIV incidence. Ensuring access to HIV services is a significant human rights issue and successful programmes require adequate human rights protections and community support. However, the cost of specific human rights and community support interventions for equitable, sustainable and non-discriminatory access to ART are not well described. Human rights and community support interventions were identified using the literature and through consultations with experts. Specific costs were then determined for these health sector interventions. Population and epidemic data were provided through the Statistics South Africa 2009 national mid-year estimates. Costs of scale up of HIV prevention and treatment were taken from recently published estimates. Interventions addressed access to services, minimising stigma and discrimination against people living with HIV, confidentiality, informed consent and counselling quality. Integrated HIV programme interventions included training for counsellors, ‘Know Your Rights’ information desks, outreach campaigns for most at risk populations, and adherence support. Complementary measures included post-service interviews, human rights abuse monitoring, transportation costs, legal assistance, and funding for human rights and community support organisations. Other essential non-health sector interventions were identified but not included in the costing framework. The annual costs for the human rights and community support interventions are United States (US) $63.8 million (US$1.22 per capita), representing 1.5% of total health sector HIV programme costs. Respect for human rights and community engagement can be understood both as an obligation of expanded ART programmes and as a critically important factor in their success. Basic rights-based and community support interventions constitute only a small percentage of overall programmes costs. ART programs should consider measuring the cost and impact of human rights and community support interventions as key aspects of successful programme expansion

Expanding ART for Treatment and Prevention of HIV in South Africa: Estimated Cost and Cost-Effectiveness 2011-2050

Background: Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa. Methods: We model a best case scenario of 90% annual HIV testing coverage in adults 15-49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm3(current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011-2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses. Results: Expanding ART to CD4 count <350 cells/mm3prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and$3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves$0.6 billion versus current; other ART scenarios cost $9-194 per DALY averted. If ART reduces transmission by 99$17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%. Conclusion: Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570