Understanding Household Dynamics From the Ground Up: A Longitudinal Study From a Rural South African Setting.

Investigations into household structure in low- and middle-income countries (LMICs) provide important insight into how families manage domestic life in response to resource allocation and caregiving needs during periods of rapid sociopolitical and health-related challenges. Recent evidence on household structure in many LMICs contrasts with long-standing viewpoints of worldwide convergence to a Western nuclearized household model. Here, we adopt a household-centered theoretical and methodological framework to investigate longitudinal patterns and dynamics of household structure in a rural South African setting during a period of high AIDS-related mortality and socioeconomic change. Data come from the Agincourt Health and Socio-Demographic Surveillance System (2003-2015). Using latent transition models, we derived six distinct household types by examining conditional interdependency between household heads' characteristics, members' age composition, and migration status. More than half of households were characterized by their complex and multigenerational profiles, with considerable within-typology variation in household size and dependency structure. Transition analyses showed stability of household types under female headship, while higher proportions of nuclearized household types dissolved over time. Household dissolution was closely linked to prior mortality experiences-particularly, following death of a male head. Our findings highlight the need to better conceptualize and contextualize household changes across populations and over time.

Estimating seroprevalence of SARS-CoV-2 in Ohio: A Bayesian multilevel poststratification approach with multiple diagnostic tests.

Globally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 59 million people and killed more than 1.39 million. Designing and monitoring interventions to slow and stop the spread of the virus require knowledge of how many people have been and are currently infected, where they live, and how they interact. The first step is an accurate assessment of the population prevalence of past infections. There are very few population-representative prevalence studies of SARS-CoV-2 infections, and only two states in the United States-Indiana and Connecticut-have reported probability-based sample surveys that characterize statewide prevalence of SARS-CoV-2. One of the difficulties is the fact that tests to detect and characterize SARS-CoV-2 coronavirus antibodies are new, are not well characterized, and generally function poorly. During July 2020, a survey representing all adults in the state of Ohio in the United States collected serum samples and information on protective behavior related to SARS-CoV-2 and coronavirus disease 2019 (COVID-19). Several features of the survey make it difficult to estimate past prevalence: 1) a low response rate; 2) a very low number of positive cases; and 3) the fact that multiple poor-quality serological tests were used to detect SARS-CoV-2 antibodies. We describe a Bayesian approach for analyzing the biomarker data that simultaneously addresses these challenges and characterizes the potential effect of selective response. The model does not require survey sample weights; accounts for multiple imperfect antibody test results; and characterizes uncertainty related to the sample survey and the multiple imperfect, potentially correlated tests.

Twin epidemics: the effects of HIV and systolic blood pressure on mortality risk in rural South Africa, 2010-2019.

BACKGROUND: Sub-Saharan African settings are experiencing dual epidemics of HIV and hypertension. We investigate effects of each condition on mortality and examine whether HIV and hypertension interact in determining mortality. METHODS: Data come from the 2010 Ha Nakekela population-based survey of individuals ages 40 and older (1,802 women; 1,107 men) nested in the Agincourt Health and socio-Demographic Surveillance System in rural South Africa, which provides mortality follow-up from population surveillance until mid-2019. Using discrete-time event history models stratified by sex, we assessed differential mortality risks according to baseline measures of HIV infection, HIV-1 RNA viral load, and systolic blood pressure. RESULTS: During the 8-year follow-up period, mortality was high (477 deaths). Survey weighted estimates are that 37% of men (mortality rate 987.53/100,000, 95% CI: 986.26 to 988.79) and 25% of women (mortality rate 937.28/100,000, 95% CI: 899.7 to 974.88) died. Over a quarter of participants were living with HIV (PLWH) at baseline, over 50% of whom had unsuppressed viral loads. The share of the population with a systolic blood pressure of 140mm Hg or higher increased from 24% at ages 40-59 to 50% at ages 75-plus and was generally higher for those not living with HIV compared to PLWH. Men and women with unsuppressed viral load had elevated mortality risks (men: adjusted odds ratio (aOR) 3.23, 95% CI: 2.21 to 4.71, women: aOR 2.05, 95% CI: 1.27 to 3.30). There was a weak, non-linear relationship between systolic blood pressure and higher mortality risk. We found no significant interaction between systolic blood pressure and HIV status for either men or women (p>0.05). CONCLUSIONS: Our results indicate that HIV and elevated blood pressure are acting as separate, non-interacting epidemics affecting high proportions of the older adult population. PLWH with unsuppressed viral load were at higher mortality risk compared to those uninfected. Systolic blood pressure was a mortality risk factor independent of HIV status. As antiretroviral therapy becomes more widespread, further longitudinal follow-up is needed to understand how the dynamics of increased longevity and multimorbidity among people living with both HIV and high blood pressure, as well as the emergence of COVID-19, may alter these patterns.

Dynamic Multicontrast X-Ray Imaging Method Applied to Additive Manufacturing.

We present a dynamic implementation of the beam-tracking x-ray imaging method providing absorption, phase, and ultrasmall angle scattering signals with microscopic resolution and high frame rate. We demonstrate the method's ability to capture dynamic processes with 22-ms time resolution by investigating the melting of metals in laser additive manufacturing, which has so far been limited to single-modality synchrotron radiography. The simultaneous availability of three contrast channels enables earlier segmentation of droplets, tracking of powder dynamic, and estimation of unfused powder amounts, demonstrating that the method can provide additional information on melting processes.

Should the SARS-CoV-2 vaccine be mandatory for nurses? An ethical debate.

The COVID-19 pandemic has had a devastating impact on the UK, as well as many other countries around the world, affecting all aspects of society. Nurses and other health and care professionals are a group particularly exposed to the virus through their work. Evidence suggests that vaccines form the most promising strategy for fighting this pandemic. Should vaccination against be mandatory for nurses and other health professionals? This article explores this question using an ethical framework.

Non-confirming replication of "Performance of InSilicoVA for assigning causes of death to verbal autopsies: multisite validation study using clinical diagnostic gold standards," by Flaxman et al.

BACKGROUND: A verbal autopsy (VA) is an interview conducted with the caregivers of someone who has recently died to describe the circumstances of the death. In recent years, several algorithmic methods have been developed to classify cause of death using VA data. The performance of one method-InSilicoVA-was evaluated in a study by Flaxman et al., published in BMC Medicine in 2018. The results of that study are different from those previously published by our group. METHODS: Based on the description of methods in the Flaxman et al. study, we attempt to replicate the analysis to understand why the published results differ from those of our previous work. RESULTS: We failed to reproduce the results published in Flaxman et al. Most of the discrepancies we find likely result from undocumented differences in data pre-processing, and/or values assigned to key parameters governing the behavior of the algorithm. CONCLUSION: This finding highlights the importance of making replication code available along with published results. All code necessary to replicate the work described here is freely available on GitHub.

Clusters of HIV Risk and Protective Sexual Behaviors in Agincourt, Rural South Africa: Findings from the Ha Nakekela Population-Based Study of Ages 15 and Older.

Understanding how sexual behaviors cluster in distinct population subgroups along the life course is critical for effective targeting and tailoring of HIV prevention messaging and intervention activities. We examined interrelatedness of sexual behaviors and variation between men and women across a wide age range in a rural South African setting with a high HIV burden. Data come from the Ha Nakekela population-based survey of people aged 15-85-plus drawn from the Agincourt Health and Socio-Demographic Surveillance System. We used latent class analysis of six sexual behavior indicators to identify distinct subgroup sexual behavior clusters. We then examined associations between class membership and sociodemographic and other behavioral risk factors and assessed the accuracy of a reduced set of sexual behavior indicators to classify individuals into latent classes. We identified three sexual behavior classes: (1) single with consistent protective behaviors; (2) risky behaviors; and (3) in union with lack of protective behaviors. Patterns of sexual behaviors varied by gender. Class membership was also associated with age, HIV status, nationality, and alcohol use. With only two sexual behavior indicators (union status and multiple sexual partners), individuals were accurately assigned to their most likely predicted class. There were distinct multidimensional sexual behavior clusters in population subgroups that varied by sex, age, and HIV status. In this population, only two brief questions were needed to classify individuals into risk classes. Replication in other situations is needed to confirm these findings.

Automated versus physician assignment of cause of death for verbal autopsies: randomized trial of 9374 deaths in 117 villages in India.

BACKGROUND: Verbal autopsies with physician assignment of cause of death (COD) are commonly used in settings where medical certification of deaths is uncommon. It remains unanswered if automated algorithms can replace physician assignment. METHODS: We randomized verbal autopsy interviews for deaths in 117 villages in rural India to either physician or automated COD assignment. Twenty-four trained lay (non-medical) surveyors applied the allocated method using a laptop-based electronic system. Two of 25 physicians were allocated randomly to independently code the deaths in the physician assignment arm. Six algorithms (Naïve Bayes Classifier (NBC), King-Lu, InSilicoVA, InSilicoVA-NT, InterVA-4, and SmartVA) coded each death in the automated arm. The primary outcome was concordance with the COD distribution in the standard physician-assigned arm. Four thousand six hundred fifty-one (4651) deaths were allocated to physician (standard), and 4723 to automated arms. RESULTS: The two arms were nearly identical in demographics and key symptom patterns. The average concordances of automated algorithms with the standard were 62%, 56%, and 59% for adult, child, and neonatal deaths, respectively. Automated algorithms showed inconsistent results, even for causes that are relatively easy to identify such as road traffic injuries. Automated algorithms underestimated the number of cancer and suicide deaths in adults and overestimated other injuries in adults and children. Across all ages, average weighted concordance with the standard was 62% (range 79-45%) with the best to worst ranking automated algorithms being InterVA-4, InSilicoVA-NT, InSilicoVA, SmartVA, NBC, and King-Lu. Individual-level sensitivity for causes of adult deaths in the automated arm was low between the algorithms but high between two independent physicians in the physician arm. CONCLUSIONS: While desirable, automated algorithms require further development and rigorous evaluation. Lay reporting of deaths paired with physician COD assignment of verbal autopsies, despite some limitations, remains a practicable method to document the patterns of mortality reliably for unattended deaths. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02810366. Submitted on 11 April 2016.

A General Age-Specific Mortality Model With an Example Indexed by Child Mortality or Both Child and Adult Mortality.

The majority of countries in Africa and nearly one-third of all countries require mortality models to infer the complete age schedules of mortality that are required to conduct population estimates, projections/forecasts, and other tasks in demography and epidemiology. Models that relate child mortality to mortality at other ages are important because almost all countries have measures of child mortality. A general, parameterizable component model (SVD-Comp) of mortality is defined using the singular value decomposition and calibrated to the relationship between child or child/adult mortality and mortality at other ages in the observed mortality schedules of the Human Mortality Database. Cross-validation is used to validate the model, and the predictive performance of the model is compared with that of the log-quadratic (Log-Quad) model, which is designed to do the same thing. Prediction and cross-validation tests indicate that the child mortality-calibrated SVD-Comp is able to accurately represent the observed mortality schedules in the Human Mortality Database, is robust to the selection of mortality schedules used for calibration, and performs better than the Log-Quad model. The child mortality-calibrated SVD-Comp can be used where and when child mortality is available but mortality at other ages is unknown.

The WHO 2016 verbal autopsy instrument: An international standard suitable for automated analysis by InterVA, InSilicoVA, and Tariff 2.0.

BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable causes of death at the population level in places where systems for medical certification of cause of death are weak. VA methods suitable for use in routine settings, such as civil registration and vital statistics (CRVS) systems, have developed rapidly in the last decade. These developments have been part of a growing global momentum to strengthen CRVS systems in low-income countries. With this momentum have come pressure for continued research and development of VA methods and the need for a single standard VA instrument on which multiple automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016, partners harmonized a WHO VA standard instrument that fully incorporates the indicators necessary to run currently available automated diagnostic algorithms. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality. This VA instrument offers the opportunity to harmonize the automated diagnostic algorithms in the future. CONCLUSIONS: Despite all improvements in design and technology, VA is only recommended where medical certification of cause of death is not possible. The method can nevertheless provide sufficient information to guide public health priorities in communities in which physician certification of deaths is largely unavailable. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality.

Sexual behavior and HIV risk across the life course in rural South Africa: trends and comparisons.

There is limited information about sexual behavior among older Africans, which is problematic given high HIV rates among older adults. We use a population-based survey among people aged 15-80+ to examine the prevalence of sexual risk and protective behaviors in the context of a severe HIV epidemic. We focus on variation across the life course, gender and HIV serostatus to compare the similarities and differences of young, middle aged, and older adults. Younger adults continue to be at risk of HIV, with potential partners being more likely to have been diagnosed with an STI and more likely to have HIV, partner change is high, and condom use is low. Middle aged and older adults engage in sexual behavior that makes them vulnerable at older ages, including extramarital sex, low condom use, and cross-generational sex with people in age groups with the highest rates of HIV. We find insignificant differences between HIV positive and negative adults' reports of recent sexual activity. This study provides new information on sexual behavior and HIV risk across the life course in rural South Africa to inform HIV prevention and treatment programing.

Probabilistic population projections for countries with generalized HIV/AIDS epidemics.

In 2015, the United Nations (UN) issued probabilistic population projections for all countries up to 2100, by simulating future levels of total fertility and life expectancy and combining the results using a standard cohort component projection method. For the 40 countries with generalized HIV/AIDS epidemics, the mortality projections used the Spectrum/Estimation and Projection Package (EPP) model, a complex, multistate model designed for short-term projections of policy-relevant quantities for the epidemic. We propose a simpler approach that is more compatible with existing UN projection methods for other countries. Changes in life expectancy are projected probabilistically using a simple time series regression and then converted to age- and sex-specific mortality rates using model life tables designed for countries with HIV/AIDS epidemics. These are then input to the cohort component method, as for other countries. The method performed well in an out-of-sample cross-validation experiment. It gives similar short-run projections to Spectrum/EPP, while being simpler and avoiding multistate modelling.

Progression of the epidemiological transition in a rural South African setting: findings from population surveillance in Agincourt, 1993-2013.

BACKGROUND: Virtually all low- and middle-income countries are undergoing an epidemiological transition whose progression is more varied than experienced in high-income countries. Observed changes in mortality and disease patterns reveal that the transition in most low- and middle-income countries is characterized by reversals, partial changes and the simultaneous occurrence of different types of diseases of varying magnitude. Localized characterization of this shifting burden, frequently lacking, is essential to guide decentralised health and social systems on the effective targeting of limited resources. Based on a rigorous compilation of mortality data over two decades, this paper provides a comprehensive assessment of the epidemiological transition in a rural South African population. METHODS: We estimate overall and cause-specific hazards of death as functions of sex, age and time period from mortality data from the Agincourt Health and socio-Demographic Surveillance System and conduct statistical tests of changes and differentials to assess the progression of the epidemiological transition over the period 1993-2013. RESULTS: From the early 1990s until 2007 the population experienced a reversal in its epidemiological transition, driven mostly by increased HIV/AIDS and TB related mortality. In recent years, the transition is following a positive trajectory as a result of declining HIV/AIDS and TB related mortality. However, in most age groups the cause of death distribution is yet to reach the levels it occupied in the early 1990s. The transition is also characterized by persistent gender differences with more rapid positive progression in females than males. CONCLUSIONS: This typical rural South African population is experiencing a protracted epidemiological transition. The intersection and interaction of HIV/AIDS and antiretroviral treatment, non-communicable disease risk factors and complex social and behavioral changes will impact on continued progress in reducing preventable mortality and improving health across the life course. Integrated healthcare planning and program delivery is required to improve access and adherence for HIV and non-communicable disease treatment. These findings from a local, rural setting over an extended period contribute to the evidence needed to inform further refinement and advancement of epidemiological transition theory.

Social patterns and differentials in the fertility transition in the context of HIV/AIDS: evidence from population surveillance, rural South Africa, 1993 - 2013.

BACKGROUND: Literature is limited on the effects of high prevalence HIV on fertility in the absence of treatment, and the effects of the introduction of sustained access to antiretroviral therapy (ART) on fertility. We summarize fertility patterns in rural northeast South Africa over 21 years during dynamic social and epidemiological change. METHODS: We use data for females aged 15-49 from the Agincourt health and socio-demographic surveillance system (1993-2013). We use discrete time event history analysis to summarize patterns in the probability of any birth. RESULTS: Overall fertility declined in 2001-2003, increased in 2004-2011, and then declined in 2012-2013. South Africans showed a similar pattern. Mozambicans showed a different pattern, with strong declines prior to 2003 before stalling during 2004-2007, and then continued fertility decline afterwards. There was an inverse gradient between fertility levels and household socioeconomic status. The gradient did not vary by time or nationality. CONCLUSIONS: The fertility transition in rural South Africa shows a pattern of decline until the height of the HIV/AIDS pandemic, with a resulting stall until further decline in the context of ART rollout. Fertility patterns are not homogenous among groups.

Bayesian population reconstruction of female populations for less developed and more developed countries.

We show that Bayesian population reconstruction, a recent method for estimating past populations by age, works for data of widely varying quality. Bayesian reconstruction simultaneously estimates age-specific population counts, fertility rates, mortality rates, and net international migration flows from fragmentary data, while formally accounting for measurement error. As inputs, Bayesian reconstruction uses initial bias-reduced estimates of standard demographic variables. We reconstruct the female populations of three countries: Laos, a country with little vital registration data where population estimation depends largely on surveys; Sri Lanka, a country with some vital registration data; and New Zealand, a country with a highly developed statistical system and good quality vital registration data. In addition, we extend the method to countries without censuses at regular intervals. We also use it to assess the consistency of results between model life tables and available census data, and hence to compare different model life table systems.

Cardiometabolic disease risk and HIV status in rural South Africa: establishing a baseline.

BACKGROUND: To inform health care and training, resource and research priorities, it is essential to establish how non-communicable disease risk factors vary by HIV-status in high HIV burden areas; and whether long-term anti-retroviral therapy (ART) plays a modifying role. METHODS: As part of a cohort initiation, we conducted a baseline HIV/cardiometabolic risk factor survey in 2010-2011 using an age-sex stratified random sample of ages 15+ in rural South Africa. We modelled cardiometabolic risk factors and their associations by HIV-status and self-reported ART status for ages 18+ using sex-stratified logistic regression models. RESULTS: Age-standardised HIV prevalence in women was 26% (95% CI 24-28%) and 19% (95% CI 17-21) in men. People with untreated HIV were less likely to have a high waist circumference in both women (OR 0.67; 95% CI 0.52-0.86) and men (OR 0.42; 95% CI 0.22-0.82). Untreated women were more likely to have low HDL and LDL, and treated women high triglycerides. Cardiometabolic risk factors increased with age except low HDL. The prevalence of hypertension was high (40% in women; 30% in men). CONCLUSIONS: Sub-Saharan Africa is facing intersecting epidemics of HIV and hypertension. In this setting, around half the adult population require long-term care for at least one of HIV, hypertension or diabetes. Together with the adverse effects that HIV and its treatment have on lipids, this may have serious implications for the South African health care system. Monitoring of the interaction of HIV, ART use, and cardiometabolic disease is needed at both individual and population levels.

The impacts of maternal mortality and cause of death on children's risk of dying in rural South Africa: evidence from a population based surveillance study (1992-2013).

BACKGROUND: Maternal mortality, the HIV/AIDS pandemic, and child survival are closely linked. This study contributes evidence on the impact of maternal death on children's risk of dying in an HIV-endemic population in rural South Africa. METHODS: We used data for children younger than 10 years from the Agincourt health and socio-demographic surveillance system (1992 - 2013). We used discrete time event history analysis to estimate children's risk of dying when they experienced a maternal death compared to children whose mother survived (N=3,740,992 child months). We also examined variation in risk due to cause of maternal death. We defined mother's survival status as early maternal death (during pregnancy, childbirth, or within 42 days of most recent childbirth or identified cause of death), late maternal death (within 43-365 days of most recent childbirth), any other death, and mothers who survived. RESULTS: Children who experienced an early maternal death were at 15 times the risk of dying (RRR 15.2; 95% CI 8.3-27.9) compared to children whose mother survived. Children under 1 month whose mother died an early (p=0.002) maternal death were at increased risk of dying compared to older children. Children whose mothers died of an HIV/AIDS or TB-related early maternal death were at 29 times the risk of dying compared to children with surviving mothers (RRR 29.2; 95% CI 11.7-73.1). The risk of these children dying was significantly higher than those children whose mother died of a HIV/AIDS or TB-related non-maternal death (p=0.017). CONCLUSIONS: This study contributes further evidence on the impact of a mother's death on child survival in a poor, rural setting with high HIV prevalence. The intersecting epidemics of maternal mortality and HIV/AIDS - especially in sub-Saharan Africa - have profound implications for maternal and child health and well-being. Such evidence can help guide public and primary health care practice and interventions.

Evidence of mycobacterial disease in COPD patients with lung volume reduction surgery; the importance of histological assessment of specimens: a cohort study.

BACKGROUND: Patients with COPD are at risk of non-tuberculous mycobacterial infection (NTM). This study examined the histology of lung tissue from COPD patients following lung volume reduction with particular focus on evidence of mycobacterial infection. METHODS: Retrospective histological study of 142 consecutive lung volume reduction surgical specimens (126 separate patients) at Royal Brompton Hospital between 2000 - 2013, with prospectively collected preoperative data on exacerbation rate, lung function and body mass index. RESULTS: 92% of patients had at least one other histological diagnosis in addition to emphysema. 10% of specimens had histological evidence of mycobacterial infection, one with co-existent aspergilloma. Mycobacteria were only identified in those patients with granulomas that were necrotising. These patients had higher exacerbation rates, lower TLCO and FEV1. CONCLUSION: A proportion of severe COPD patients will have evidence of mycobacterial infection despite lack of clinical and radiological suspicion. This may have implications for long-term management of these patients.