Variation in the Proportion of Adults in Need of Blood Pressure-Lowering Medications by Hypertension Care Guideline in Low- and Middle-Income Countries: A Cross-Sectional Study of 1 037 215 Individuals From 50 Nationally Representative Surveys.

BACKGROUND: Current hypertension guidelines vary substantially in their definition of who should be offered blood pressure-lowering medications. Understanding the effect of guideline choice on the proportion of adults who require treatment is crucial for planning and scaling up hypertension care in low- and middle-income countries. METHODS: We extracted cross-sectional data on age, sex, blood pressure, hypertension treatment and diagnosis status, smoking, and body mass index for adults 30 to 70 years of age from nationally representative surveys in 50 low- and middle-income countries (N = 1 037 215). We aimed to determine the effect of hypertension guideline choice on the proportion of adults in need of blood pressure-lowering medications. We considered 4 hypertension guidelines: the 2017 American College of Cardiology/American Heart Association guideline, the commonly used 140/90 mm Hg threshold, the 2016 World Health Organization HEARTS guideline, and the 2019 UK National Institute for Health and Care Excellence guideline. RESULTS: The proportion of adults in need of blood pressure-lowering medications was highest under the American College of Cardiology/American Heart Association, followed by the 140/90 mm Hg, National Institute for Health and Care Excellence, and World Health Organization guidelines (American College of Cardiology/American Heart Association: women, 27.7% [95% CI, 27.2-28.2], men, 35.0% [95% CI, 34.4-35.7]; 140/90 mm Hg: women, 26.1% [95% CI, 25.5-26.6], men, 31.2% [95% CI, 30.6-31.9]; National Institute for Health and Care Excellence: women, 11.8% [95% CI, 11.4-12.1], men, 15.7% [95% CI, 15.3-16.2]; World Health Organization: women, 9.2% [95% CI, 8.9-9.5], men, 11.0% [95% CI, 10.6-11.4]). Individuals who were unaware that they have hypertension were the primary contributor to differences in the proportion needing treatment under different guideline criteria. Differences in the proportion needing blood pressure-lowering medications were largest in the oldest (65-69 years) age group (American College of Cardiology/American Heart Association: women, 60.2% [95% CI, 58.8-61.6], men, 70.1% [95% CI, 68.8-71.3]; World Health Organization: women, 20.1% [95% CI, 18.8-21.3], men, 24.1.0% [95% CI, 22.3-25.9]). For both women and men and across all guidelines, countries in the European and Eastern Mediterranean regions had the highest proportion of adults in need of blood pressure-lowering medicines, whereas the South and Central Americas had the lowest. CONCLUSIONS: There was substantial variation in the proportion of adults in need of blood pressure-lowering medications depending on which hypertension guideline was used. Given the great implications of this choice for health system capacity, policy makers will need to carefully consider which guideline they should adopt when scaling up hypertension care in their country.

CD4+ T-Cell Count at Antiretroviral Therapy Initiation in the "Treat-All" Era in Rural South Africa: An Interrupted Time Series Analysis.

BACKGROUND: South Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART). METHODS: We therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults aged ≥16 years attending 17 public sector primary care clinics in rural South Africa, between July 2014 and March 2019. RESULTS: Among 20 599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/µL (95% confidence interval [CI], 308.6 to 325.6) 1 to 8 months prior to UTT to 421.0 cells/µL (95% CI, 413.0 to 429.0) 1 to 12 months after UTT, including an immediate increase of 124.2 cells/µL (95% CI, 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/µL (95% CI, 381.8 to 397.1) 13 to 30 months after UTT but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (-118.2 cells/µL, 95% CI, -125.5 to -111.0) throughout the study. CONCLUSIONS: Although UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in those living with human immunodeficiency virus, particularly men.

Body-mass index and diabetes risk in 57 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data in 685 616 adults.

BACKGROUND: The prevalence of overweight, obesity, and diabetes is rising rapidly in low-income and middle-income countries (LMICs), but there are scant empirical data on the association between body-mass index (BMI) and diabetes in these settings. METHODS: In this cross-sectional study, we pooled individual-level data from nationally representative surveys across 57 LMICs. We identified all countries in which a WHO Stepwise Approach to Surveillance (STEPS) survey had been done during a year in which the country fell into an eligible World Bank income group category. For LMICs that did not have a STEPS survey, did not have valid contact information, or declined our request for data, we did a systematic search for survey datasets. Eligible surveys were done during or after 2008; had individual-level data; were done in a low-income, lower-middle-income, or upper-middle-income country; were nationally representative; had a response rate of 50% or higher; contained a diabetes biomarker (either a blood glucose measurement or glycated haemoglobin [HbA1c]); and contained data on height and weight. Diabetes was defined biologically as a fasting plasma glucose concentration of 7·0 mmol/L (126·0 mg/dL) or higher; a random plasma glucose concentration of 11·1 mmol/L (200·0 mg/dL) or higher; or a HbA1c of 6·5% (48·0 mmol/mol) or higher, or by self-reported use of diabetes medication. We included individuals aged 25 years or older with complete data on diabetes status, BMI (defined as normal [18·5-22·9 kg/m2], upper-normal [23·0-24·9 kg/m2], overweight [25·0-29·9 kg/m2], or obese [≥30·0 kg/m2]), sex, and age. Countries were categorised into six geographical regions: Latin America and the Caribbean, Europe and central Asia, east, south, and southeast Asia, sub-Saharan Africa, Middle East and north Africa, and Oceania. We estimated the association between BMI and diabetes risk by multivariable Poisson regression and receiver operating curve analyses, stratified by sex and geographical region. FINDINGS: Our pooled dataset from 58 nationally representative surveys in 57 LMICs included 685 616 individuals. The overall prevalence of overweight was 27·2% (95% CI 26·6-27·8), of obesity was 21·0% (19·6-22·5), and of diabetes was 9·3% (8·4-10·2). In the pooled analysis, a higher risk of diabetes was observed at a BMI of 23 kg/m2 or higher, with a 43% greater risk of diabetes for men and a 41% greater risk for women compared with a BMI of 18·5-22·9 kg/m2. Diabetes risk also increased steeply in individuals aged 35-44 years and in men aged 25-34 years in sub-Saharan Africa. In the stratified analyses, there was considerable regional variability in this association. Optimal BMI thresholds for diabetes screening ranged from 23·8 kg/m2 among men in east, south, and southeast Asia to 28·3 kg/m2 among women in the Middle East and north Africa and in Latin America and the Caribbean. INTERPRETATION: The association between BMI and diabetes risk in LMICs is subject to substantial regional variability. Diabetes risk is greater at lower BMI thresholds and at younger ages than reflected in currently used BMI cutoffs for assessing diabetes risk. These findings offer an important insight to inform context-specific diabetes screening guidelines. FUNDING: Harvard T H Chan School of Public Health McLennan Fund: Dean's Challenge Grant Program.

Maternal iron-and-folic-acid supplementation and its association with low-birth weight and neonatal mortality in India.

OBJECTIVE: The current study assessed intake of iron-and-folic-acid (IFA) tablet/syrup (grouped into none, < 100 d of IFA consumption or < 100 IFA and ≥ 100 d of IFA consumption or ≥ 100 IFA) among prospective mothers and its association with various stages of low-birth weight (ELBW, extremely low-birth weight; VLBW, very low-birth weight and LBW, low-birth weight) and neonatal mortality (death during day 0-1, 2-6, 7-27 and 0-27) in India. DESIGN: The cross-sectional, nationally representative, 2015-2016 National Family Health Survey (NFHS-4) data were used. Weighted descriptive analysis and multiple binary logistic regression modelling were used. SETTING: NFHS-4 covered 640 districts from thirty-seven states and union territories of India. PARTICIPANTS: A total of 120 374 and 143 675 index children aged 0-59 months were included to analyse LBW and neonatal mortality, respectively. RESULTS: Overall, 30·7 % mothers consumed ≥ 100 IFA in 2015-2016, and this estimate ranged from 0·0 % in Zunheboto district of Nagaland state to 89·5 % in Mahe district of Puducherry of India. Multiple regression analysis revealed that children of mothers who consumed ≥ 100 IFA had lower odds of ELBW, VLBW, LBW and neonatal mortality during day 0-1, as compared with mothers who did not buy/receive any IFA. Consumption of IFA (< 100 IFA and ≥ 100 IFA) had a protective association with neonatal death during day 7-27 and 0-27. Consumption of IFA was not associated with neonatal death during day 2-6. CONCLUSIONS: While ≥ 100 IFA consumption during pregnancy was found to be associated with preventing select types of LBW and neonatal mortality, a large variation in coverage of ≥ 100 IFA consumption across 640 districts is concerning.

Semiparametric linear transformation models for indirectly observed outcomes.

We propose a regression framework to analyze outcomes that are indirectly observed via one or multiple proxies. Semiparametric transformation models, including Cox proportional hazards regression, turn out to be well suited to model the association between the covariates and the unobserved outcome. By coupling this regression model to a semiparametric measurement model, we can estimate these associations without requiring calibration data and without imposing strong functional assumptions on the relationship between the unobserved outcome and its proxy. When multiple proxies are available, we propose a data-driven aggregation resulting in an improved proxy. We empirically validate the proposed methodology in a simulation study, revealing good finite sample properties, especially when multiple proxies are aggregated. The methods are demonstrated on two case studies.

The Impact of Immediate Initiation of Antiretroviral Therapy on Patients' Healthcare Expenditures: A Stepped-Wedge Randomized Trial in Eswatini.

Immediate initiation of antiretroviral therapy (ART) for all people living with HIV has important health benefits but implications for the economic aspects of patients' lives are still largely unknown. This stepped-wedge cluster-randomized controlled trial aimed to determine the causal impact of immediate ART initiation on patients' healthcare expenditures in Eswatini. Fourteen healthcare facilities were randomly assigned to transition at one of seven time points from the standard of care (ART eligibility below a CD4 count threshold) to the immediate ART for all intervention (EAAA). 2261 patients living with HIV were interviewed over the study period to capture their past-year out-of-pocket healthcare expenditures. In mixed-effects regression models, we found a 49% decrease (RR 0.51, 95% CI 0.36, 0.72, p < 0.001) in past-year total healthcare expenditures in the EAAA group compared to the standard of care, and a 98% (RR 0.02, 95% CI 0.00, 0.02, p < 0.001) decrease in spending on private and traditional healthcare. Despite a higher frequency of HIV care visits for newly initiated ART patients, immediate ART initiation appears to have lowered patients' healthcare expenditures because they sought less care from alternative healthcare providers. This study adds an important economic argument to the World Health Organization's recommendation to abolish CD4-count-based eligibility thresholds for ART.

RESUMEN: El inicio inmediato de la terapia antirretroviral (TAR) para todas las personas que viven con VIH tiene importantes beneficios para la salud, pero aún se desconocen las implicaciones en el aspecto económico. Este ensayo controlado aleatorizado por clústers (CRT por sus siglas en inglés) por grupos en distintas etapas pretende determinar el impacto del inicio inmediato de la TAR en los gastos sanitarios de los pacientes en Eswatini. Catorce centros sanitarios fueron asignados aleatoriamente a la transición en uno de los siete periodos de la asistencia estándar (elegibilidad para la TAR en niveles definidos de recuento de CD4) a la intervención de TAR inmediato para todos (EAAA). Se entrevistó a 2.261 pacientes con VIH a lo largo del estudio para conocer sus gastos sanitarios del año anterior. Según los modelos de regresión de efectos mixtos, se observó un descenso del 49% (RR: 0,51; IC del 95%: 0,36, 0,72; p<0,001) en el gasto sanitario total del año anterior en el grupo de la EAAA, y un descenso del 98% (RR 0,02; IC del 95%: 0,00, 0,02; p<0,001) en el gasto en asistencia sanitaria privada y tradicional. A pesar de una mayor frecuencia de visitas deatención de VIH para los pacientes que recién comenzaron laTAR, la aplicación inmediata de laTAR redujo los gastos sanitarios de los pacientes dado que buscaron menos atención de proveedores de asistencia sanitaria alternativos. Este estudio añade un importante argumento económico a la recomendación de la Organización Mundial de la Salud de abolir las restricciones de elegibilidad para la terapia antirretroviral basados en el recuento de CD4.

Children's education and parental old-age health: Evidence from a population-based, nationally representative study in India.

Previous research has documented intergenerational transmission of human capital from children to parents. Less is known, however, about heterogeneity in this 'upward transmission' in low-resource settings. We examine whether co-resident adult children's education is associated with improved health among older parents in India, using nationally representative data from the 2014 Indian National Sample Survey. Parents of children with tertiary education had a lower probability of reporting poor health than parents of children with less than primary education. The benefits of children's education persisted after controlling for economic factors, suggesting that non-pecuniary pathways-such as health knowledge or skills-may play an important role. The association was more pronounced among economically dependent parents and those living in the North and West regions. Taken together, our results point to a strong positive association between children's education and parental health, the role of non-pecuniary pathways, and the importance of subnational heterogeneity in India.

Nationally and regionally representative analysis of 1.65 million children aged under 5 years using a child-based human development index: A multi-country cross-sectional study.

BACKGROUND: Education and health are both constituents of human capital that enable people to earn higher wages and enhance people's capabilities. Human capabilities may lead to fulfilling lives by enabling people to achieve a valuable combination of human functionings-i.e., what people are able to do or be as a result of their capabilities. A better understanding of how these different human capabilities are produced together could point to opportunities to help jointly reduce the wide disparities in health and education across populations. METHODS AND FINDINGS: We use nationally and regionally representative individual-level data from Demographic and Health Surveys (DHS) for 55 low- and middle-income countries (LMICs) to examine patterns in human capabilities at the national and regional levels, between 2000 and 2017 (N = 1,657,194 children under age 5). We graphically analyze human capabilities, separately for each country, and propose a novel child-based Human Development Index (HDI) based on under-five survival, maternal educational attainment, and measures of a child's household wealth. We normalize the range of each component using data on the minimum and maximum values across countries (for national comparisons) or first-level administrative units within countries (for subnational comparisons). The scores that can be generated by the child-based HDI range from 0 to 1. We find considerable heterogeneity in child health across countries as well as within countries. At the national level, the child-based HDI ranged from 0.140 in Niger (with mean across first-level administrative units = 0.277 and standard deviation [SD] 0.114) to 0.755 in Albania (with mean across first-level administrative units = 0.603 and SD 0.089). There are improvements over time overall between the 2000s and 2010s, although this is not the case for all countries included in our study. In Cambodia, Malawi, and Nigeria, for instance, under-five survival improved over time at most levels of maternal education and wealth. In contrast, in the Philippines, we found relatively few changes in under-five survival across the development spectrum and over time. In these countries, the persistent location of geographical areas of poor child health across both the development spectrum and time may indicate within-country poverty traps. Limitations of our study include its descriptive nature, lack of information beyond first- and second-level administrative units, and limited generalizability beyond the countries analyzed. CONCLUSIONS: This study maps patterns and trends in human capabilities and is among the first, to our knowledge, to introduce a child-based HDI at the national and subnational level. Areas of chronic deprivation may indicate within-country poverty traps and require alternative policy approaches to improving child health in low-resource settings.

The impact of continuous quality improvement on coverage of antenatal HIV care tests in rural South Africa: Results of a stepped-wedge cluster-randomised controlled implementation trial.

BACKGROUND: Evidence for the effectiveness of continuous quality improvement (CQI) in resource-poor settings is very limited. We aimed to establish the effects of CQI on quality of antenatal HIV care in primary care clinics in rural South Africa. METHODS AND FINDINGS: We conducted a stepped-wedge cluster-randomised controlled trial (RCT) comparing CQI to usual standard of antenatal care (ANC) in 7 nurse-led, public-sector primary care clinics-combined into 6 clusters-over 8 steps and 19 months. Clusters randomly switched from comparator to intervention on pre-specified dates until all had rolled over to the CQI intervention. Investigators and clusters were blinded to randomisation until 2 weeks prior to each step. The intervention was delivered by trained CQI mentors and included standard CQI tools (process maps, fishbone diagrams, run charts, Plan-Do-Study-Act [PDSA] cycles, and action learning sessions). CQI mentors worked with health workers, including nurses and HIV lay counsellors. The mentors used the standard CQI tools flexibly, tailored to local clinic needs. Health workers were the direct recipients of the intervention, whereas the ultimate beneficiaries were pregnant women attending ANC. Our 2 registered primary endpoints were viral load (VL) monitoring (which is critical for elimination of mother-to-child transmission of HIV [eMTCT] and the health of pregnant women living with HIV) and repeat HIV testing (which is necessary to identify and treat women who seroconvert during pregnancy). All pregnant women who attended their first antenatal visit at one of the 7 study clinics and were ≥18 years old at delivery were eligible for endpoint assessment. We performed intention-to-treat (ITT) analyses using modified Poisson generalised linear mixed effects models. We estimated effect sizes with time-step fixed effects and clinic random effects (Model 1). In separate models, we added a nested random clinic-time step interaction term (Model 2) or individual random effects (Model 3). Between 15 July 2015 and 30 January 2017, 2,160 participants with 13,212 ANC visits (intervention n = 6,877, control n = 6,335) were eligible for ITT analysis. No adverse events were reported. Median age at first booking was 25 years (interquartile range [IQR] 21 to 30), and median parity was 1 (IQR 0 to 2). HIV prevalence was 47% (95% CI 42% to 53%). In Model 1, CQI significantly increased VL monitoring (relative risk [RR] 1.38, 95% CI 1.21 to 1.57, p < 0.001) but did not improve repeat HIV testing (RR 1.00, 95% CI 0.88 to 1.13, p = 0.958). These results remained essentially the same in both Model 2 and Model 3. Limitations of our study include that we did not establish impact beyond the duration of the relatively short study period of 19 months, and that transition steps may have been too short to achieve the full potential impact of the CQI intervention. CONCLUSIONS: We found that CQI can be effective at increasing quality of primary care in rural Africa. Policy makers should consider CQI as a routine intervention to boost quality of primary care in rural African communities. Implementation research should accompany future CQI use to elucidate mechanisms of action and to identify factors supporting long-term success. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov under registration number NCT02626351.

Are out-of-school adolescents at higher risk of adverse health outcomes? Evidence from 9 diverse settings in sub-Saharan Africa.

OBJECTIVES: We analysed mutually comparable surveys on adolescent attitudes and behaviours from nine sites in seven sub-Saharan African countries, to determine the relationship between school enrolment and adolescent health outcomes. METHODS: Data from the Africa Research, Implementation Science, and Education Network cross-sectional adolescent health surveys were used to examine the associations of current school enrolment, self-reported general health and four major adolescent health domains: (i) sexual and reproductive health; (ii) nutrition and non-communicable diseases; (iii) mental health, violence and injury; and (iv) healthcare utilisation. We used multivariable Poisson regression models to calculate relative risk ratios with 95% confidence intervals (CI), controlling for demographic and socio-economic characteristics. We assessed heterogeneity by gender and study site. RESULTS: Across 7829 adolescents aged 10-19, 70.5% were in school at the time of interview. In-school adolescents were 14.3% more likely (95% CI: 6-22) to report that their life is going well; 51.2% less likely (95% CI: 45-67) to report ever having had sexual intercourse; 32.6% more likely (95% CI: 9-61) to report unmet need for health care; and 30.1% less likely (95% CI: 15-43) to report having visited a traditional healer. School enrolment was not significantly associated with malnutrition, low mood, violence or injury. Substantial heterogeneity was identified between genders for sexual and reproductive health, and in-school adolescents were particularly less likely to report adverse health outcomes in settings with high average school enrolment. CONCLUSIONS: School enrolment is strongly associated with sexual and reproductive health and healthcare utilisation outcomes across nine sites in sub-Saharan Africa. Keeping adolescents in school may improve key health outcomes, something that can be explored through future longitudinal, mixed-methods, and (quasi-)experimental studies.

OBJECTIFS: Nous avons analysé des enquêtes mutuellement comparables sur les attitudes et les comportements d'adolescents dans neuf sites dans sept pays d'Afrique subsaharienne, afin de déterminer la relation entre la scolarisation et les résultats de la santé des adolescents. MÉTHODES: Des données provenant d'enquêtes transversales sur la santé des adolescents menées par le Réseau Africain de Recherche, d'Implémentation, de Science et d'Education ont été utilisées pour examiner les associations existant entre la scolarisation, l'état de santé général autodéclaré et les quatre principaux domaines de la santé des adolescents: (i) santé sexuelle et reproductive ; (ii) nutrition et maladies non transmissibles; (iii) santé mentale, violence et blessures et (iv) utilisation des soins de santé. Nous avons utilisé des modèles de régression multivariée de Poisson pour calculer les rapports de risque relatifs avec des intervalles de confiance (IC) à 95%, en tenant compte des caractéristiques démographiques et socioéconomiques. Nous avons évalué l'hétérogénéité par sexe et par site d'étude. RÉSULTATS: Sur 7.829 adolescents âgés de 10 à 19 ans, 70,5% étaient à l'école au moment de l'enquête. Les adolescents scolarisés étaient 14,3% (IC95%: 6-22) plus susceptibles de déclarer que leur vie se passait bien, 51,2% (IC95%: 45-67) moins susceptibles de déclarer avoir déjà eu des rapports sexuels, 32,6% (IC95%: 39-91) plus susceptibles de signaler un besoin de soins de santé non satisfait et 30,1% (IC95%: 15-43) moins susceptibles de déclarer avoir rendu visite à un guérisseur traditionnel. La scolarisation n'était pas associée de manière significative à la malnutrition, à la mauvaise humeur, à la violence ou aux blessures. Une hétérogénéité substantielle a été identifiée entre les sexes pour la santé sexuelle et reproductive, et les adolescents scolarisés étaient particulièrement moins susceptibles de faire état de résultats défavorables pour la santé dans les milieux où la moyenne de scolarisation était élevée. CONCLUSIONS: La scolarisation est fortement associée aux résultats en matière de santé sexuelle et reproductive et d'utilisation des soins de santé dans neuf sites en Afrique subsaharienne. Garder les adolescents à l'école peut améliorer les principaux résultats de santé, ce qui peut être exploré dans le cadre de futures études longitudinales.

Lifetime Prevalence of Cervical Cancer Screening in 55 Low- and Middle-Income Countries.

Importance: The World Health Organization is developing a global strategy to eliminate cervical cancer, with goals for screening prevalence among women aged 30 through 49 years. However, evidence on prevalence levels of cervical cancer screening in low- and middle-income countries (LMICs) is sparse. Objective: To determine lifetime cervical cancer screening prevalence in LMICs and its variation across and within world regions and countries. Design, Setting, and Participants: Analysis of cross-sectional nationally representative household surveys carried out in 55 LMICs from 2005 through 2018. The median response rate across surveys was 93.8% (range, 64.0%-99.3%). The population-based sample consisted of 1 136 289 women aged 15 years or older, of whom 6885 (0.6%) had missing information for the survey question on cervical cancer screening. Exposures: World region, country; countries' economic, social, and health system characteristics; and individuals' sociodemographic characteristics. Main Outcomes and Measures: Self-report of having ever had a screening test for cervical cancer. Results: Of the 1 129 404 women included in the analysis, 542 475 were aged 30 through 49 years. A country-level median of 43.6% (interquartile range [IQR], 13.9%-77.3%; range, 0.3%-97.4%) of women aged 30 through 49 years self-reported to have ever been screened, with countries in Latin America and the Caribbean having the highest prevalence (country-level median, 84.6%; IQR, 65.7%-91.1%; range, 11.7%-97.4%) and those in sub-Saharan Africa the lowest prevalence (country-level median, 16.9%; IQR, 3.7%-31.0%; range, 0.9%-50.8%). There was large variation in the self-reported lifetime prevalence of cervical cancer screening among countries within regions and among countries with similar levels of per capita gross domestic product and total health expenditure. Within countries, women who lived in rural areas, had low educational attainment, or had low household wealth were generally least likely to self-report ever having been screened. Conclusions and Relevance: In this cross-sectional study of data collected in 55 low- and middle-income countries from 2005 through 2018, there was wide variation between countries in the self-reported lifetime prevalence of cervical cancer screening. However, the median prevalence was only 44%, supporting the need to increase the rate of screening.

On the interpretation of the hazard ratio in Cox regression.

We argue that the term "relative risk" should not be used as a synonym for "hazard ratio" and encourage to use the probabilistic index as an alternative effect measure for Cox regression. The probabilistic index is the probability that the event time of an exposed or treated subject exceeds the event time of an unexposed or untreated subject conditional on the other covariates. It arises as a well known and simple transformation of the hazard ratio and nicely reveals the interpretational limitations. We demonstrate how the probabilistic index can be obtained using the R-package Publish.

Expansion of HIV testing in Eswatini: stakeholder perspectives on reaching the first 90.

Achieving the United Nations' 90-90-90 goals has proven challenging in most settings and the ambitious 95-95-95 goals seem even more elusive. However, in Eswatini - a lower-middle-income country in sub-Saharan Africa with the highest HIV prevalence in the world - an estimated 92% of people living with HIV know their status. We conducted 26 in-depth interviews with stakeholders from policy, implementation, donor, local advocacy and academic sectors to elicit the facilitators and inhibitors to HIV testing uptake in Eswatini. Background data and related reports and policy documents (n = 57) were also reviewed. Essential facilitators included good governance via institutional and national budgetary commitments, which often led to swift adoption of globally recommended programs and standards. The integration of HIV testing into all points of care fostered a sense that testing was part of routine care, which reduced stigma. Challenges, however, centred on social norms that disadvantage certain groups with high ongoing HIV risk (such as key populations, adolescent girls and young women), a heavy reliance on external donor funding, and stigma that had subsided but nevertheless persisted. Amid concerns about whether the 90-90-90 targets could be achieved by 2020, the experience of Eswatini provides tangible insights into factors that have successfully influenced HIV testing uptake and may thus prove informative for other countries.

Semiparametric linear transformation models: Effect measures, estimators, and applications.

Semiparametric linear transformation models form a versatile class of regression models with the Cox proportional hazards model being the most well-known member. These models are well studied for right censored outcomes and are typically used in survival analysis. We consider transformation models as a tool for situations with uncensored continuous outcomes where linear regression is not appropriate. We introduce the probabilistic index as a uniform effect measure for the class of transformation models. We discuss and compare three estimators using a working Cox regression model: the partial likelihood estimator, an estimator based on binary generalized linear models and one based on probabilistic index model estimating equations. The latter has a superior performance in terms of bias and variance when the working model is misspecified. For the purpose of illustration, we analyze data that were collected at an urban alcohol and drug detoxification unit.

Kenya's Health in All Policies strategy: a policy analysis using Kingdon's multiple streams.

BACKGROUND: Health in All Policies (HiAP) is an intersectoral approach that facilitates decision-making among policy-makers to maximise positive health impacts of other public policies. Kenya, as a member of WHO, has committed to adopting HiAP, which has been included in the Kenya Health Policy for the period 2014-2030. This study aims to assess the extent to which this commitment is being translated into the process of governmental policy-making and supported by international development partners as well as non-state actors. METHODS: To examine HiAP in Kenya, a qualitative case study was performed, including a review of relevant policy documents. Furthermore, 40 key informants with diverse backgrounds (government, UN agencies, development agencies, civil society) were interviewed. Analysis was carried out using the main dimensions of Kingdon's Multiple Streams Approach (problems, policy, politics). RESULTS: Kenya is facing major health challenges that are influenced by various social determinants, but the implementation of intersectoral action focusing on health promotion is still arbitrary. On the policy level, little is known about HiAP in other government ministries. Many health-related collaborations exist under the concept of intersectoral collaboration, which is prominent in the country's development framework - Vision 2030 - but with no specific reference to HiAP. Under the political stream, the study highlights that political commitment from the highest office would facilitate mainstreaming the HiAP strategy, e.g. by setting up a department under the President's Office. The budgeting process and planning for the Sustainable Development Goals were found to be potential windows of opportunity. CONCLUSION: While HiAP is being adopted as policy in Kenya, it is still perceived by many stakeholders as the business of the health sector, rather than a policy for the whole government and beyond. Kenya's Vision 2030 should use HiAP to foster progress in all sectors with health promotion as an explicit goal.

Causal Effect of Parental Schooling on Early Childhood Undernutrition: Quasi-Experimental Evidence From Zimbabwe.

An estimated 3.1 million children die each year because of undernutrition. Although cross-sectional and longitudinal studies have found a protective association between greater parental education and undernutrition in their children, no randomized trial has identified a causal effect, to our knowledge. Using the 1980 education reform in Zimbabwe as a natural experiment, we estimated the causal effect of additional parental schooling on the probability of anthropometric failure in their children under 5 years of age (ages 3 through 59 months). Analyzing data on 8,243 children from the 1988, 1999, 2005-2006, and 2010-2011 Demographic and Health Surveys, we found no effect of parental schooling on early childhood undernutrition at the national level in Zimbabwe. Among households in the urban and high-wealth-index subsamples, each additional year of maternal schooling led to absolute reductions in the probability of a child's being wasted of 5.2 percentage points (95% confidence interval (CI): -9.3, -1.2) and 3.6 percentage points (95% CI: -6.9, -0.4), respectively. In the subsample of children between the ages of 3 and 23 months, each additional year of paternal schooling increased the probability of a child's being stunted by 9.6 percentage points (95% CI: 1.4, 17.9). Secondary schooling alone may not be enough to improve early childhood nutrition in low-resource settings.

The MONARCH intervention to enhance the quality of antenatal and postnatal primary health services in rural South Africa: protocol for a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Gaps in maternal and child health services can slow progress towards achieving the Sustainable Development Goals. The Management and Optimization of Nutrition, Antenatal, Reproductive, Child Health & HIV Care (MONARCH) study will evaluate a Continuous Quality Improvement (CQI) intervention targeted at improving antenatal and postnatal health service outcomes in rural South Africa where HIV prevalence among pregnant women is extremely high. Specifically, it will establish the effectiveness of CQI on viral load (VL) testing in pregnant women who are HIV-positive and repeat HIV testing in pregnant women who are HIV-negative. METHODS: This is a stepped-wedge cluster-randomised controlled trial (RCT) of 7 nurse-led primary healthcare clinics to establish the effect of CQI on selected routine antenatal and postnatal services. Each clinic was a cluster, with the exception of the two smallest clinics, which jointly formed one cluster. The intervention was applied at the cluster level, where staff received training on CQI methodology and additional mentoring as required. In the control exposure state, the clusters received the South African Department of Health standard of care. After a baseline data collection period of 2 months, the first cluster crossed over from control to intervention exposure state; subsequently, one additional cluster crossed over every 2 months. The six clusters were divided into 3 groups by patient volume (low, medium and high). We randomised the six clusters to the sequences of crossing over, such that both the first three and the last three sequences included one cluster with low, one with medium, and one with high patient volume. The primary outcome measures were (i) viral load testing among pregnant women who were HIV-positive, and (ii) repeat HIV testing among pregnant women who were HIV-negative. Consenting women ≥18 years attending antenatal and postnatal care during the data collection period completed outcome measures at delivery, and postpartum at three to 6 days, and 6 weeks. Data collection started on 15 July 2015. The total study duration, including pre- and post-exposure phases, was 19 months. Data will be analyzed by intention-to-treat based on first booked clinic of study participants. DISCUSSION: The results of the MONARCH trial will establish the effectiveness of CQI in improving antenatal and postnatal clinic processes in primary care in sub-Saharan Africa. More generally, the results will contribute to our knowledge on quality improvement interventions in resource-poor settings. TRIAL REGISTRATION: This trial was registered on 10 December 2015: www.clinicaltrials.gov, identifier NCT02626351 .

Harmonization of community health worker programs for HIV: A four-country qualitative study in Southern Africa.

BACKGROUND: Community health worker (CHW) programs are believed to be poorly coordinated, poorly integrated into national health systems, and lacking long-term support. Duplication of services, fragmentation, and resource limitations may have impeded the potential impact of CHWs for achieving HIV goals. This study assesses mediators of a more harmonized approach to implementing large-scale CHW programs for HIV in the context of complex health systems and multiple donors. METHODS AND FINDINGS: We undertook four country case studies in Lesotho, Mozambique, South Africa, and Swaziland between August 2015 and May 2016. We conducted 60 semistructured interviews with donors, government officials, and expert observers involved in CHW programs delivering HIV services. Interviews were triangulated with published literature, country reports, national health plans, and policies. Data were analyzed based on 3 priority areas of harmonization (coordination, integration, and sustainability) and 5 components of a conceptual framework (the health issue, intervention, stakeholders, health system, and context) to assess facilitators and barriers to harmonization of CHW programs. CHWs supporting HIV programs were found to be highly fragmented and poorly integrated into national health systems. Stakeholders generally supported increasing harmonization, although they recognized several challenges and disadvantages to harmonization. Key facilitators to harmonization included (i) a large existing national CHW program and recognition of nongovernmental CHW programs, (ii) use of common incentives and training processes for CHWs, (iii) existence of an organizational structure dedicated to community health initiatives, and (iv) involvement of community leaders in decision-making. Key barriers included a wide range of stakeholders and lack of ownership and accountability of non-governmental CHW programs. Limitations of our study include subjectively selected case studies, our focus on decision-makers, and limited generalizability beyond the countries analyzed. CONCLUSION: CHW programs for HIV in Southern Africa are fragmented, poorly integrated, and lack long-term support. We provide 5 policy recommendations to harmonize CHW programs in order to strengthen and sustain the role of CHWs in HIV service delivery.

Household coverage of Swaziland's national community health worker programme: a cross-sectional population-based study.

OBJECTIVES: To ascertain household coverage achieved by Swaziland's national community health worker (CHW) programme and differences in household coverage across clients' sociodemographic characteristics. METHODS: Household survey from June to September 2015 in two of Swaziland's four administrative regions using two-stage cluster random sampling. Interviewers administered a questionnaire to all household members in 1542 households across 85 census enumeration areas. RESULTS: While the CHW programme aims to cover all households in the country, only 44.5% (95% confidence interval: 38.0% to 51.1%) reported that they had ever been visited by a CHW. In both uni- and multivariable regressions, coverage was negatively associated with household wealth (OR for most vs. least wealthy quartile: 0.30 [0.16 to 0.58], P < 0.001) and education (OR for >secondary schooling vs. no schooling: 0.65 [0.47 to 0.90], P = 0.009), and positively associated with residing in a rural area (OR: 2.95 [1.77 to 4.91], P < 0.001). Coverage varied widely between census enumeration areas. CONCLUSIONS: Swaziland's national CHW programme is falling far short of its coverage goal. To improve coverage, the programme would likely need to recruit additional CHWs and/or assign more households to each CHW. Alternatively, changing the programme's ambitious coverage goal to visiting only certain types of households would likely reduce existing arbitrary differences in coverage between households and communities. This study highlights the need to evaluate and reform large long-standing CHW programmes in sub-Saharan Africa.

Improving the performance of community health workers in Swaziland: findings from a qualitative study.

BACKGROUND: The performance of community health workers (CHWs) in Swaziland has not yet been studied despite the existence of a large national CHW program in the country. This qualitative formative research study aimed to inform the design of future interventions intended to increase the performance of CHW programs in Swaziland. Specifically, focusing on four CHW programs, we aimed to determine what potential changes to their program CHWs and CHW program managers perceive as likely leading to improved performance of the CHW cadre. METHODS: The CHW cadres studied were the rural health motivators, mothers-to-mothers (M2M) mentors, HIV expert clients, and a community outreach team for HIV. We conducted semi-structured, face-to-face qualitative interviews with all (15) CHW program managers and a purposive sample of 54 CHWs. Interview transcripts were analyzed using conventional content analysis to identify categories of changes to the program that participants perceived would result in improved CHW performance. RESULTS: Across the four cadres, participants perceived the following four changes to likely lead to improved CHW performance: (i) increased monetary compensation of CHWs, (ii) a more reliable supply of equipment and consumables, (iii) additional training, and (iv) an expansion of CHW responsibilities to cover a wider array of the community's healthcare needs. The supervision of CHWs and opportunities for career progression were rarely viewed as requiring improvement to increase CHW performance. CONCLUSIONS: While this study is unable to provide evidence on whether the suggested changes would indeed lead to improved CHW performance, these views should nonetheless inform program reforms in Swaziland because CHWs and CHW program managers are familiar with the day-to-day operations of the program and the needs of the target population. In addition, program reforms that agree with their views would likely experience a higher degree of buy-in from these frontline health workers.