Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis

BACKGROUND: Paediatric multidrug-resistant (MDR) tuberculosis is a public health challenge of growing concern, accounting for an estimated 15% of all global cases of MDR tuberculosis. Clinical management is especially challenging, and recommendations are based on restricted evidence. We aimed to assess existing evidence for the treatment of MDR tuberculosis in children. METHODS: We did a systematic review and meta-analysis of published and unpublished studies reporting treatment outcomes for children with MDR tuberculosis. We searched PubMed, Ovid, Embase, Cochrane Library, PsychINFO, and BioMedCentral databases up to Oct 31, 2011. Eligible studies included five or more children (aged ≤16 years) with MDR tuberculosis within a defined treatment cohort. The primary outcome was treatment success, defined as a composite of cure and treatment completion. RESULTS: We identified eight studies, which reported treatment outcomes for a total of 315 patients. We recorded much variation in the characteristics of patients and programmes. Time to appropriate treatment varied from 2 days to 46 months. Average duration of treatment ranged from 6 months to 34 months, and duration of follow-up ranged from 12 months to 37 months. The pooled estimate for treatment success was 81·67% (95% CI 72·54-90·80). Across all studies, 5·9% (95% CI 1·3-10·5) died, 6·2% (2·3-10·2) defaulted, and 39·1% (28·7-49·4) had an adverse event. The most common drug-related adverse events were nausea and vomiting. Other serious adverse events were hearing loss, psychiatric effects, and hypothyroidism. INTERPRETATION: The treatment of paediatric MDR tuberculosis has been neglected, but when children are treated outcomes can be achieved that are at least as good as those reported for adults. Programmes should be encouraged to report outcomes in children to improve the knowledge base for care, especially as new drugs become available. FUNDING: None

Impact of HIV-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010

Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS)

Regional Adoption of Business-to-Business Electronic Commerce in China: Role of E-Readiness

Adoption of B2B e-commerce is a powerful driver of economic success in developed and developing countries. However, adoption rates in developing countries lag far behind. This paper draws on the Perceived eReadiness Model and research on the influence of inter-organizational relationships and economic-cultural contexts to explain the importance of three factors—inter-organizational power dependence, cooperativeness, and regional economic-cultural differences—for achieving higher levels of Internet-based Electronic Data Interchange (EDI) in the developing country of China. We employ survey data to empirically test both the individual and joint influence of these factors. The findings suggest that beyond intra-organizational and external factors, managers and policy makers wanting to promote Internet-based EDI adoption in developing countries must also account for the inter-organizational relationships of firms and the economic and cultural circumstances of the regions in which they operate

Association of BMI Category Change with TB Treatment Mortality in HIV-Positive Smear-Negative and Extrapulmonary TB Patients in Myanmar and Zimbabwe

OBJECTIVE: The HIV epidemic has increased the proportion of patients with smear-negative and extrapulmonary tuberculosis (TB) diagnoses, with related higher rates of poor TB treatment outcomes. Unlike in smear-positive pulmonary TB, no interim markers of TB treatment progress are systematically used to identify individuals most at risk of mortality. The objective of this study was to assess the association of body mass index (BMI) change at 1 month (±15 days) from TB treatment start with mortality among HIV-positive individuals with smear-negative and extrapulmonary TB. METHODS AND FINDINGS: A retrospective cohort study of adult HIV-positive new TB patients in Médecins Sans Frontières (MSF) treatment programmes in Myanmar and Zimbabwe was conducted using Cox proportional hazards regression to estimate the association between BMI category change and mortality. A cohort of 1090 TB patients (605 smear-negative and 485 extrapulmonary) was followed during TB treatment with mortality rate of 28.9 per 100 person-years. In multivariable analyses, remaining severely underweight or moving to a lower BMI category increased mortality (adjusted hazard ratio 4.05, 95% confidence interval 2.77-5.91, p<0.001) compared with remaining in the same or moving to a higher BMI category. CONCLUSIONS: We found a strong association between BMI category change during the first month of TB treatment and mortality. BMI category change could be used to identify individuals most at risk of mortality during TB treatment among smear-negative and extrapulmonary patients

The Secreted Metalloprotease ADAMTS20 Is Required for Melanoblast Survival

ADAMTS20 (A disintegrin-like and metalloprotease domain with thrombospondin type-1 motifs) is a member of a family of secreted metalloproteases that can process a variety of extracellular matrix (ECM) components and secreted molecules. Adamts20 mutations in belted (bt) mice cause white spotting of the dorsal and ventral torso, indicative of defective neural crest (NC)-derived melanoblast development. The expression pattern of Adamts20 in dermal mesenchymal cells adjacent to migrating melanoblasts led us to initially propose that Adamts20 regulated melanoblast migration. However, using a Dct-LacZ transgene to track melanoblast development, we determined that melanoblasts were distributed normally in whole mount E12.5 bt/bt embryos, but were specifically reduced in the trunk of E13.5 bt/bt embryos due to a seven-fold higher rate of apoptosis. The melanoblast defect was exacerbated in newborn skin and embryos from bt/bt animals that were also haploinsufficient for Adamts9, a close homolog of Adamts20, indicating that these metalloproteases functionally overlap in melanoblast development. We identified two potential mechanisms by which Adamts20 may regulate melanoblast survival. First, skin explant cultures demonstrated that Adamts20 was required for melanoblasts to respond to soluble Kit ligand (sKitl). In support of this requirement, bt/bt;Kittm1Alf/+ and bt/bt;KitlSl/+ mice exhibited synergistically increased spotting. Second, ADAMTS20 cleaved the aggregating proteoglycan versican in vitro and was necessary for versican processing in vivo, raising the possibility that versican can participate in melanoblast development. These findings reveal previously unrecognized roles for Adamts proteases in cell survival and in mediating Kit signaling during melanoblast colonization of the skin. Our results have implications not only for understanding mechanisms of NC-derived melanoblast development but also provide insights on novel biological functions of secreted metalloproteases

Molecular Chemistry to the Fore: New Insights into the Fascinating World of Photoactive Colloidal Semiconductor Nanocrystals

Colloidal semiconductor nanocrystals possess unique properties that are unmatched by other chromophores such as organic dyes or transition-metal complexes. These versatile building blocks have generated much scientific interest and found applications in bioimaging, tracking, lighting, lasing, photovoltaics, photocatalysis, thermoelectrics, and spintronics. Despite these advances, important challenges remain, notably how to produce semiconductor nanostructures with predetermined architecture, how to produce metastable semiconductor nanostructures that are hard to isolate by conventional syntheses, and how to control the degree of surface loading or valence per nanocrystal. Molecular chemists are very familiar with these issues and can use their expertise to help solve these challenges. In this Perspective, we present our group\u27s recent work on bottom-up molecular control of nanoscale composition and morphology, low-temperature photochemical routes to semiconductor heterostructures and metastable phases, solar-to-chemical energy conversion with semiconductor-based photocatalysts, and controlled surface modification of colloidal semiconductors that bypasses ligand exchange