Systematic review of studies generating individual participant data on the efficacy of drugs for treating soil-transmitted helminthiases and the case for data-sharing

Preventive chemotherapy and transmission control (PCT) by mass drug administration is the cornerstone of the World Health Organization (WHO)’s policy to control soil-transmitted helminthiases (STHs) caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm) and hookworm species (Necator americanus and Ancylostama duodenale) which affect over 1 billion people globally. Despite consensus that drug efficacies should be monitored for signs of decline that could jeopardise the effectiveness of PCT, systematic monitoring and evaluation is seldom implemented. Drug trials mostly report aggregate efficacies in groups of participants, but heterogeneities in design complicate classical meta-analyses of these data. Individual participant data (IPD) permit more detailed analysis of drug efficacies, offering increased sensitivity to identify atypical responses potentially caused by emerging drug resistance

Assessing health and well-being among older people in rural South Africa

Background: The population in developing countries is ageing, which is likely to increase the burden of noncommunicable diseases and disability. Objective: To describe factors associated with self-reported health, disability and quality of life (QoL) of older people in the rural northeast of South Africa. Design: Cross-sectional survey of 6,206 individuals aged 50 and over. We used multivariate analysis to examine relationships between demographic variables and measures of self-reported health (Health Status), functional ability (WHODASi) and quality of life (WHOQoL). Results: About 4,085 of 6,206 people eligible (65.8%) completed the interview. Women (Odds Ratio (OR) 1.30, 95% CI 1.09, 1.55), older age (OR2.59, 95% CI 1.97, 3.40), lower education (OR1.62, 95% CI 1.31,2.00), single status (OR1.18, 95% CI 1.01, 1.37) and not working at present (OR1.29, 95% CI 1.06, 1.59) were associated with a low health status. Women were also more likely to report a higher level of disability (OR1.38, 95% CI 1.14, 1.66), as were older people (OR2.92, 95% CI 2.25, 3.78), those with no education (OR1.57, 95% CI 1.26, 1.97), with single status (OR1.25, 95% CI 1.06, 1.46) and not working at present (OR1.33, 95% CI 1.06, 1.66). Older age (OR1.35, 95% CI 1.06, 1.74), no education (OR1.39, 95% CI 1.11, 1.73), single status (OR1.28, 95% CI 1.10, 1.49), a low household asset score (OR1.52, 95% CI 1.19, 1.94) and not working at present (OR1.32; 95% CI 1.07, 1.64) were all associated with lower quality of life. Conclusions: This study presents the first population-based data from South Africa on health status, functional ability and quality of life among older people. Health and social services will need to be restructured to provide effective care for older people living in rural South Africa with impaired functionality and other health problems

Clinical deterioration during antituberculosis treatment in Africa: Incidence, causes and risk factors

BACKGROUND:HIV-1 and Mycobacterium tuberculosis cause substantial morbidity and mortality. Despite the availability of antiretroviral and antituberculosis treatment in Africa, clinical deterioration during antituberculosis treatment remains a frequent reason for hospital admission. We therefore determined the incidence, causes and risk factors for clinical deterioration. METHODS: Prospective cohort study of 292 adults who initiated antituberculosis treatment during a 3-month period. We evaluated those with clinical deterioration over the following 24 weeks of treatment. RESULTS: Seventy-one percent (209/292) of patients were HIV-1 infected (median CD4+: 129 cells/muL [IQR:62-277]). At tuberculosis diagnosis, 23% (34/145) of HIV-1 infected patients qualifying for antiretroviral treatment (ART) were receiving ART; 6 months later, 75% (109/145) had received ART. Within 24 weeks of initiating antituberculosis treatment, 40% (117/292) of patients experienced clinical deterioration due to co-morbid illness (n = 70), tuberculosis related illness (n = 47), non AIDS-defining HIV-1 related infection (n = 25) and AIDS-defining illness (n = 21). Using HIV-1 uninfected patients as the referent group, HIV-1 infected patients had an increasing risk of clinical deterioration as CD4+ counts decreased [CD4+>350 cells/muL: RR = 1.4, 95% CI = 0.7-2.9; CD4+:200-350 cells/muL: RR = 2.0, 95% CI = 1.1-3.6; CD4+<200 cells/muL: RR = 3.0, 95% CI = 1.9-4.7]. During follow-up, 26% (30/117) of patients with clinical deterioration required hospital admission and 15% (17/117) died. Fifteen deaths were in HIV-1 infected patients with a CD4+<200 cells/muL. CONCLUSIONS: In multivariate analysis, HIV-1 infection and a low CD4+ count at tuberculosis diagnosis were significant risk factors for clinical deterioration and death. The initiation of ART at a CD4+ count of <350 cells/muL will likely reduce the high burden of clinical deterioration

A systems approach identifies co-signaling molecules of early growth response 1 transcription factor in immobilization stress

Adaptation to stress is critical for survival. The adrenal medulla, the major source of epinephrine, plays an important role in the development of the hyperadenergic state and increased risk for stress associated disorders, such as hypertension and myocardial infarction. The transcription factor Egr1 plays a central role in acute and repeated stress, however the complexity of the response suggests that other transcription factor pathways might be playing equally important roles during acute and repeated stress. Therefore, we sought to discover such factors by applying a systems approach. Using microarrays and network analysis we show here for the first time that the transcription factor signal transducer and activator of transcription 3 (Stat3) gene is activated in acute stress whereas the prolactin releasing hormone (Prlh11) and chromogranin B (Chgb) genes are induced in repeated immobilization stress and that along with Egr1 may be critical mediators of the stress response. Our results suggest possible involvement of Stat3 and Prlh1/Chgb up-regulation in the transition from short to repeated stress activation