Moving from medical to health systems classifications of deaths : extending verbal autopsy to collect information on the circumstances of mortality

Acknowledgements The authors would also like to acknowledge the field staff at the MRC, SA/Wits Agincourt Unit, particularly Sizzy Ngobeni. The authors also acknowledge Drs Malin Eriksson and Edward Fottrell at Umeå Centre for Global Health Research *UCGHR) who contributed to the development of the SF-VA indicators, Dr Nawi Ng at UCGHR who advised on the cause of death categories, and Dr Kerstin Edin at UCGHR who provided comments on the manuscript categories, and Dr Kerstin Edin who provided comments on the manuscript. Funding A Health Systems Research Initiative Development Grant from the UK Department for International Development (DFID), Economic and Social Research Council (ESRC), Medical Research Council (MRC (and the Wellcome Trust (MR/N005597/1) funds the research presented in this paper. Support for the Agincourt HDSS including verbal autopsies was provided by The Wellcome Trust, UK (grants 058893/Z/99/A; 069683/Z/02/Z; 085477/Z/08/Z; 085477/B/08/Z), and the University of the Witwatersrand and Medical Research Council, South Africa.Peer reviewedPublisher PD

Variation by Geographic Scale in the Migration-Environment Association: Evidence from Rural South Africa

"Scholarly understanding of human migration's environmental dimensions has greatly advanced in the past several years, motivated in large part by public and policy dialogue around 'climate migrants'. The research presented here advances current demographic scholarship both through its substantive interpretations and conclusions, as well as its methodological approach. We examine temporary rural South African outmigration as related to household-level availability of proximate natural resources. Such 'natural capital' is central to livelihoods in the region, both for sustenance and as materials for market-bound products. The results demonstrate that the association between local environmental resource availability and outmigration is, in general, positive: households with higher levels of proximate natural capital are more likely to engage in temporary migration. In this way, the general findings support the 'environmental surplus' hypothesis that resource security provides a foundation from which households can invest in migration as a livelihood strategy. Such insight stands in contrast to popular dialogue, which tends to view migration as a last resort undertaken only by the most vulnerable households. As another important insight, our findings demonstrate important spatial variation, complicating attempts to generalize migration-environment findings across spatial scales. In our rural South African study site, the positive association between migration and proximate resources is actually highly localized, varying from strongly positive in some villages to strongly negative in others. We explore the socio-demographic factors underlying this 'operational scale sensitivity'. The cross-scale methodologies applied here offer nuance unavailable within more commonly used global regression models, although also introducing complexity that complicates story-telling and inhibits generalizability." (author's abstract

Prevalence and risk factors for active convulsive epilepsy in rural northeast South Africa

Rationale: Epilepsy is among the most common neurological disorders worldwide. However,there are few large, population-based studies of the prevalence and risk factors for epilepsy in southern Africa. Methods: From August 2008 to February 2009, as part of a multi-site study, we undertook a three-stage, population-based study, embedded within the Agincourt health and socio-demographic surveillance system, to estimate the prevalence and identify risk factors of active convulsiveepilepsy (ACE) in a rural South African population. Results: The crude prevalence of ACE, after adjusting for non-response and the sensitivity of the screening method, was 7.0/1,000 individuals (95%CI 6.4—7.6) with significant geographic hetero-geneity across the study area. Being male (OR = 2.3; 95%CI 1.6—3.2), family history of seizures(OR = 4.0; 95%CI 2.0—8.1), a sibling with seizures (OR = 7.0; 95%CI 1.6—31.7), problems after deliv-ery (OR = 5.9; 95%CI 1.2—24.6), and history of snoring (OR = 6.5; 95%CI 4.5—9.5) were significantlyassociated with ACE. For children, their mother’s exposure to some formal schooling was pro-tective (OR = 0.30; 95%CI 0.11—0.84) after controlling for age and sex. Human immunodeficiencyvirus was not found to be associated with ACE. Conclusions: ACE is less frequent in this part of rural South Africa than other parts of sub-SaharanAfrica. Improving obstetric services could prevent epilepsy. The relationship between snoring and ACE requires further investigation, as does the relative contribution of genetic and environmental factors to examine the increased risk in those with a family history of epilepsy

A Successful Failure: Missing the MDG4 Target for Under-Five Mortality in South Africa.

Reflecting on under-five mortality, Peter Byass and colleagues consider how some countries may fail to meet millennium development goal targets despite making considerable advances

Collective efficacy, alcohol outlet density, and young men’s alcohol use in rural South Africa

Alcohol use contributes to morbidity and mortality in developing countries by increasing the risk of trauma and disease, including alcohol dependence. Limited research addresses determinants of alcohol use beyond the individual level in sub-Saharan Africa. We test the association of community collective efficacy and alcohol outlet density with young men's drinking in a cross-sectional, locally representative survey conducted in rural northeast South Africa. Informal social control and cohesion show protective associations with men's heavy drinking, while alcohol outlet density is associated with more potential problem drinking. These findings provide initial support for intervening at the community level to promote alcohol reduction

The CLEAR (considering leading experts' antithrombotic regimes around peripheral angioplasty) survey: an international perspective on antiplatelet and anticoagulant practice for peripheral arterial endovascular intervention.

Background Antiplatelet and anticoagulant therapy are commonly used before, during and after peripheral arterial endovascular intervention. This survey aimed to establish antiplatelet and anticoagulant choice for peripheral arterial endovascular intervention in contemporary clinical practice. Methods Pilot-tested questionnaire distributed via collaborative research networks. Results One hundred and sixty-two complete responses were collected from responders in 22 countries, predominantly the UK (48%) and the rest of the European Union (44%). Antiplatelet monotherapy was the most common choice pre-procedurally (62%). In the UK, there was no difference between dual and single antiplatelet therapy use post procedure (50% vs. 37% p = 0.107). However, a significant majority of EU respondents used dual therapy (68% vs. 20% p < 0.001). There was variation in choice of antiplatelet therapy by the device used and the anatomical location of the intervention artery. The majority (82%) of respondents believed there was insufficient evidence to guide antithrombotic therapy after peripheral endovascular intervention and most (92%) would support a randomised trial. Conclusions There is widespread variation in the use of antiplatelet therapy, especially post peripheral arterial endovascular intervention. Clinicians would support the development of a randomised trial comparing dual antiplatelet therapy with monotherapy

Evaluation of the Tsima community mobilization intervention to improve engagement in HIV testing and care in South Africa: study protocol for a cluster randomized trial

Abstract Background HIV transmission can be decreased substantially by reducing the burden of undiagnosed HIV infection and expanding early and consistent use of antiretroviral therapy (ART). Treatment as prevention (TasP) has been proposed as key to ending the HIV epidemic. To activate TasP in high prevalence countries, like South Africa, communities must be motivated to know their status, engage in care, and remain in care. Community mobilization (CM) has the potential to significantly increase uptake testing, linkage to and retention in care by addressing the primary social barriers to engagement with HIV care—including poor understanding of HIV care; fear and stigma associated with infection, clinic attendance and disclosure; lack of social support; and gender norms that deter men from accessing care. Methods/design Using a cluster randomized trial design, we are implementing a 3-year-theory-based CM intervention and comparing gains in HIV testing, linkage, and retention in care among individuals residing in 8 intervention communities to that of individuals residing in 7 control communities. Eligible communities include 15 villages within a health and demographic surveillance site (HDSS) in rural Mpumalanga, South Africa, that were not exposed to previous CM efforts. CM activities conducted in the 8 intervention villages map onto six mobilization domains that comprise the key components for community mobilization around HIV prevention. To evaluate the intervention, we will link a clinic-based electronic clinical tracking system in all area clinics to the HDSS longitudinal census data, thus creating an open, population-based cohort with over 30,000 18–49-year-old residents. We will estimate the marginal effect of the intervention on individual outcomes using generalized estimating equations. In addition, we will evaluate CM processes by conducting baseline and endline surveys among a random sample of 1200 community residents at each time point to monitor intervention exposure and community level change using validated measures of CM. Discussion Given the known importance of community social factors with regard to uptake of testing and HIV care, and the lack of rigorously evaluated community-level interventions effective in improving testing uptake, linkage and retention, the proposed study will yield much needed data to understand the potential of CM to improve the prevention and care cascade. Further, our work in developing a CM framework and domain measures will permit validation of a CM conceptual framework and process, which should prove valuable for community programming in Africa. Trial Registration NCT02197793 Registered July 21, 2014

Gene expression and splicing alterations analyzed by high throughput RNA sequencing of chronic lymphocytic leukemia specimens.

BackgroundTo determine differentially expressed and spliced RNA transcripts in chronic lymphocytic leukemia specimens a high throughput RNA-sequencing (HTS RNA-seq) analysis was performed.MethodsTen CLL specimens and five normal peripheral blood CD19+ B cells were analyzed by HTS RNA-seq. The library preparation was performed with Illumina TrueSeq RNA kit and analyzed by Illumina HiSeq 2000 sequencing system.ResultsAn average of 48.5 million reads for B cells, and 50.6 million reads for CLL specimens were obtained with 10396 and 10448 assembled transcripts for normal B cells and primary CLL specimens respectively. With the Cuffdiff analysis, 2091 differentially expressed genes (DEG) between B cells and CLL specimens based on FPKM (fragments per kilobase of transcript per million reads and false discovery rate, FDR q &lt; 0.05, fold change &gt;2) were identified. Expression of selected DEGs (n = 32) with up regulated and down regulated expression in CLL from RNA-seq data were also analyzed by qRT-PCR in a test cohort of CLL specimens. Even though there was a variation in fold expression of DEG genes between RNA-seq and qRT-PCR; more than 90 % of analyzed genes were validated by qRT-PCR analysis. Analysis of RNA-seq data for splicing alterations in CLL and B cells was performed by Multivariate Analysis of Transcript Splicing (MATS analysis). Skipped exon was the most frequent splicing alteration in CLL specimens with 128 significant events (P-value &lt;0.05, minimum inclusion level difference &gt;0.1).ConclusionThe RNA-seq analysis of CLL specimens identifies novel DEG and alternatively spliced genes that are potential prognostic markers and therapeutic targets. High level of validation by qRT-PCR for a number of DEG genes supports the accuracy of this analysis. Global comparison of transcriptomes of B cells, IGVH non-mutated CLL (U-CLL) and mutated CLL specimens (M-CLL) with multidimensional scaling analysis was able to segregate CLL and B cell transcriptomes but the M-CLL and U-CLL transcriptomes were indistinguishable. The analysis of HTS RNA-seq data to identify alternative splicing events and other genetic abnormalities specific to CLL is an added advantage of RNA-seq that is not feasible with other genome wide analysis