Assessment of the Potential Impact and Cost-effectiveness of Self-Testing for HIV in Low-Income Countries.

Studies have demonstrated that self-testing for human immunodeficiency virus (HIV) is highly acceptable among individuals and could allow cost savings, compared with provider-delivered HIV testing and counseling (PHTC), although the longer-term population-level effects are uncertain. We evaluated the cost-effectiveness of introducing self-testing in 2015 over a 20-year time frame in a country such as Zimbabwe

Targeting the ATP-dependent formation of herpesvirus ribonucleoprotein particle assembly as an antiviral approach

Human herpesviruses are responsible for a range of debilitating acute and recurrent diseases, including a number of malignancies. Current treatments are limited to targeting the herpesvirus DNA polymerases, however with emerging viral resistance and little efficacy against the oncogenic herpesviruses, there is an urgent need for new antiviral strategies. Herein we describe a mechanism to inhibit the replication of the oncogenic herpesvirus Kaposi’s sarcoma associated herpesvirus (KSHV), by targeting the ATP-dependent formation of viral ribonucleoprotein particles (vRNPs). We demonstrate that small molecule inhibitors which selectively inhibit the ATPase activity of the cellular human transcription/export complex (hTREX) protein UAP56, result in effective inhibition of vRNP formation, viral lytic replication and infectious virion production. Strikingly, as all human herpesviruses utilize conserved mRNA processing pathways involving hTREX components, we demonstrate the feasibility of this approach for pan-herpesvirus inhibition

Opportunities for improving the efficiency of paediatric HIV treatment programmes

Objectives: To conduct two economic analyses addressing whether to: routinely monitor HIV-infected children on antiretroviral therapy (ART) clinically or with laboratory tests; continue or stop cotrimoxazole prophylaxis when children become stabilized on ART. Design and methods: The ARROW randomized trial investigated alternative strategies to deliver paediatric ART and cotrimoxazole prophylaxis in 1206 Ugandan/Zimbabwean children. Incremental cost-effectiveness and value of implementation analyses were undertaken. Scenario analyses investigated whether laboratory monitoring (CD4 tests for efficacy monitoring; haematology/biochemistry for toxicity) could be tailored and targeted to be delivered cost-effectively. Cotrimoxazole use was examined in malaria-endemic and non-endemic settings. Results: Using all trial data, clinical monitoring delivered similar health outcomes to routine laboratory monitoring, but at a reduced cost, so was cost-effective. Continuing cotrimoxazole improved health outcomes at reduced costs. Restricting routine CD4+ monitoring to after 52 weeks following ART initiation and removing toxicity testing was associated with an incremental cost-effectiveness ratio of $6084 per quality-adjusted life-year (QALY) across all age groups, but was much lower for older children (12+ years at initiation; incremental cost-effectiveness ratio =$769/QALY). Committing resources to improve cotrimoxazole implementation appears cost-effective. A healthcare system that could pay $600/QALY should be willing to spend up to$12.0 per patient-year to ensure continued provision of cotrimoxazole. Conclusion: Clinically driven monitoring of ART is cost-effective in most circumstances. Routine laboratory monitoring is generally not cost-effective at current prices, except possibly CD4 testing amongst adolescents initiating ART. Committing resources to ensure continued provision of cotrimoxazole in health facilities is more likely to represent an efficient use of resources

A variable amplitude fretting fatigue life estimation technique: formulation and experimental validation

The aims of the research work summarised in this paper are twofold. The first goal is to make available a large number of new experimental results generated by testing specimens of grey cast iron under both constant and variable amplitude fretting fatigue loading. The second goal is to formulate an advanced fretting fatigue design approach based on the combined use of the Modified Wӧhler Curve Method, the Theory of Critical Distances and the Shear Stress-Maximum Variance Method. The validation exercise based on the experimental results being produced demonstrates that the proposed methodology is a powerful tool suitable for designing mechanical assemblies against fretting fatigue

Factors associated with healthcare seeking behaviour for children in Malawi: 2016

Objective: To characterise health seeking behaviour (HSB) and determine its predictors amongst children in Malawi in 2016. Methods: We used the 2016 Malawi Integrated Household Survey data set. The outcome of interest was HSB, defined as seeking care at a health facility amongst people who reported one or more of a list of possible symptoms given on the questionnaire in the past two weeks. We fitted a multivariate logistic regression model of HSB using a forward step-wise selection method, with age, sex and symptoms entered as a priori variables. Results: Of 5350 children, 1666 (32%) had symptoms in the past two weeks. Of the 1666, 1008 (61%) sought care at health facility. The children aged 5–14 years were less likely to be taken to health facilities for health care than those aged 0–4 years. Having fever vs. not having fever and having a skin problem vs. not having skin problem were associated with increased likelihood of HSB. Having a headache vs. not having a headache was associated with lower likelihood of accessing care at health facilities (AOR = 0.50, 95% CI: 0.26–0.96, P = 0.04). Children from urban areas were more likely to be taken to health facilities for health care (AOR = 1.81, 95% CI: 1.17–2.85, P = 0.008), as were children from households with a high wealth status (AOR = 1.86, 95% CI: 1.25–2.78, P = 0.02). Conclusion: There is a need to understand and address individual, socio-economic and geographical barriers to health seeking to increase access and use of health care and fast-track progress towards Universal Health Coverage