Predictors of longitudinal change in bone mineral density in a cohort of HIV-positive and negative subjects.

OBJECTIVE: Although low bone mineral density (BMD) is prevalent in HIV, changes in BMD over time remain unclear. We aimed to compare rates of, and factors associated with, BMD change between HIV-positive and HIV-negative subjects. METHODS: In a prospective, 3-year cohort, HIV-positive and HIV-negative subjects provided annual demographic and clinical data, fasting bloods and dual x-ray absorptiometry (DXA). Using longitudinal mixed models we compared and determined predictors of rate of change in BMD. RESULTS: Of 384 subjects (45.8% HIV-positive), 120 contributed two and 264 contributed three BMD measurements. Those with HIV were younger (median (IQR) 39 (34-46) vs 43 (35-50) years; p=0.04), more often male (61% vs 46%; p = 0.003) and less likely Caucasian (61% vs 82%; p 30 years, Caucasian ethnicity, and not being on ART during follow-up were associated with greater decline and higher parathyroid hormone associated with a smaller decline in BMD at the femoral neck. We found no association between BMD change and exposure to tenofovir disoproxil fumarate or protease inhibitors. CONCLUSIONS: We observed no difference in rate of BMD decline regardless of HIV status and in HIV positive subject, having started ART within the previous three months was the only factor associated with greater BMD decline at all 3 sites

'HepCheck Dublin': An Intensified Hepatitis C Screening Programme in a Homeless Population Demonstrates the Need for Alternative Models of Care

Background: Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. Prevalence of HCV in homeless populations ranges from 3.9% to 36.2%. The HepCheck study sought to investigate and establish the characterisation of HCV burden among individuals who attended an intensified screening programme for HCV in homeless services in Dublin, Ireland. Methods: The HepCheck study was conducted as part of a larger European wide initiative called HepCare Europe. The study consisted of three phases; 1) all subjects completed a short survey and were offered a rapid oral HCV test; 2) a convenience sample of HCV positive participants from phase 1 were selected to complete a survey on health and social risk factors and 3) subjects were tracked along the referral pathway to identify whether they were referred to a specialist clinic, attended the specialist clinic, were assessed for cirrhosis by transient elastography (Fibroscan) and were treated for HCV. Results: 597 individuals were offered HCV screening, 73% were male and 63% reported having had a previous HCV screening. We screened 538 (90%) of those offered screening, with 37% testing positive. Among those who tested positive, 112 (56%) were ‘new positives’ and 44% were ‘known positives’. Undiagnosed HCV was prevalent in 19% of the study sample. Active past 30-day drug use was common, along with attendance for drug treatment. Unstable accommodation was the most common barrier to attending specialist appointments and accessing treatment. Depression and anxiety, dental problems and respiratory conditions were common reported health problems. 46 subjects were referred to specialised services and two subjects completed HCV treatment. Conclusions: This study demonstrates that the current hospital-based model of care is inadequate in addressing the specific needs of a homeless population and emphasises the need for a community-based treatment approach. Findings are intended to inform HepCare Europe in their development of a community-based model of care in order to engage with homeless individuals with multiple co-morbidities including substance abuse, who are affected by or infected with HCV

The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Introduction Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 <100 cells/mm3. We investigated the cost‐effectiveness of this enhanced‐prophylaxis package versus other strategies, including using cryptococcal antigen (CrAg) testing, in individuals with CD4 <200 cells/mm3 or <100 cells/mm3 at ART initiation and all individuals regardless of CD4 count. Methods The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 <200 cells/mm3 population providing enhanced‐prophylaxis components are sourced at lowest available prices. The ICER reduced in more severely immunosuppressed individuals (US$113 per QALY in the CD4 <100 cells/mm3 population) and increased in all individuals regardless of CD4 count (US$722 per QALY). Results were sensitive to prices of the enhanced‐prophylaxis components. Enhanced‐prophylaxis was more effective and less costly than all CrAg testing strategies as enhanced‐prophylaxis still conveyed health gains in CrAg‐negative patients and savings from targeting prophylaxis based on CrAg status did not compensate for costs of CrAg testing. CrAg testing strategies did not become cost‐effective unless the price of CrAg testing fell below US$2.30. Conclusions The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices

Late Presentation With HIV in Africa: Phenotypes, Risk, and Risk Stratification in the REALITY Trial.

This article has been accepted for publication in Clinical Infectious Diseases Published by Oxford University PressBackground: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts .1). Results: Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P < .04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P = .02). Of five late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/µL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/µL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/µL), but low symptom burden and maintained fat mass. The remaining groups had 4%-6% mortality. Conclusions: Clinical and laboratory features identified groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up. Clinical Trials Registration: ISRCTN43622374.REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation

Mapping the medical outcomes study HIV health survey (MOS-HIV) to the EuroQoL 5 Dimension (EQ-5D-3L) utility index

10.1186/s12955-019-1135-8Health and Quality of Life Outcomes1718

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

Evaluation of cystatin C in malignancy and comparability of estimates of GFR in oncology patients

Objectives: Creatinine is the biomarker of choice for use in estimates of kidney function in oncology patients. However as non-renal factors such as muscle mass can influence creatinine concentrations, we evaluated cystatin C as an alternative biomarker and its incorporation in GFR estimating formulae in an oncology setting. Measured GFR is infrequently undertaken in adult clinical practice with the consequent reliance on calculated GFR for patient assessment. Design and methods: Cystatin C and creatinine concentrations were evaluated from 134 oncology patients prior to commencing chemotherapeutic cycles. Estimates of creatinine clearance (Cockroft-Gault) and GFR (using Hoek, Jonsson, MDRD and CKD-EPI) were evaluated. Cystatin C-based GFR estimates (using CKD-EPI CysC and CKD-EPI SCr/CysC) were compared with the creatinine-based GFR estimates (CG, MDRD and CKD-EPI SCr) within the GFR ranges of 60–89, 45–59 and ≤44 mL/min/1.73 m2. Results: Cystatin C concentrations were significantly higher in oncology patients both prior to commencing chemotherapy (F: P<0.01 and M: P<0.0001) and during cycles of treatment (F: P<0.0001 and M: P<0.01) when compared with a reference population. Cystatin C concentrations also increased significantly during chemotherapy (P<0.0001) in a subset of female patients evaluated. Poor agreement (average 42%) was demonstrated between CKD-EPI CysC and creatinine-based GFR estimates within the investigated GFR ranges, with improved agreement (average 55%) when using the combined CKD-EPI SCr/CysC formula. Conclusions: This study demonstrated a malignancy and treatment-mediated effect on cystatin C measures, which may confound its clinical utility in estimating GFR in oncology patients. Keywords: Cystatin C, Kidney, GFR, Chemotherap

Pulmonary hypertension in children aged two to twenty four months hospitalised with severe pneumonia at two tertiary hospitals in Harare, Zimbabwe

Objectives: The aim of the study was to describe the echocardiographic findings in children hospitalized with severe pneumonia, in particular the presence of pulmonary hypertension. Design:&nbsp; A descriptive cross-sectional study was undertaken. Setting:&nbsp; Paediatric medical wards in two tertiary, teaching hospitals in Harare, Zimbabwe. Subjects:&nbsp; Consecutive sampling of 206 children aged 2 to 24 months meeting the WHO case definition of severe pneumonia whose caregivers gave informed consent. Main Outcome Measures: Echocardiography findings of left ventricular contractility and estimated pulmonary hypertension defined as elevated Right Ventricular Systolic Pressure (RVSP) &gt;25mmHg, both assessed by 2D echocardiography. Results:&nbsp;&nbsp; Elevated RVSP was found in 11.3% (n=22/195) of the participants with a mean of 35(4.2). This was not significantly associated with mortality (p=0.291). The following factors were significantly associated with elevated RVSP (p=&lt;0.05): central cyanosis, SPO2 &lt; 90% and at least two previous hospitalizations with pneumonia. Most, 98% (n=191) of patients had normal left ventricular contractility based on ejection fraction and fractional shortening. Ten of the participants died (10/195), giving a case fatality rate of 5.1%. Conclusion: Pulmonary hypertension was found to be a complication in 11.3% of children hospitalized with severe pneumonia. Further studies are needed to evaluate its persistence

Understanding Conceptualizations of Pregnancy and Planning for Pregnancy Among Adolescent Girls and Young Women in Harare, Zimbabwe

Zimbabwe has one of the highest rates of maternal mortality, yet little is understood about adolescent girls’ and young women’s perspectives on pregnancy or planning for pregnancy. The research study took an emic approach to understand and describe how adolescent girls and young women (14–24 years) in Harare, Zimbabwe, conceptualize pregnancy and planning for pregnancy and how these conceptualizations inform pregnancy decisions. Semi-structured, in-depth, qualitative interviews were conducted with adolescent girls and young women (N = 48) and data were analyzed thematically using NVivo 10. Pregnancy was conceptualized across nine themes: carrying a child and oneself, growing a family, motherhood, the best time for pregnancy, pregnancy decision makers, who is responsible for the pregnancy, pregnancy burden, pregnancy dangers, and increase in social status with pregnancy. Planning for pregnancy was conceptualized during the prepregnancy, pregnancy, and postpregnancy phases. Findings emphasize considering sociocultural views concerning pregnancy and including social networks in maternal health efforts