Treatment Outcomes of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

BACKGROUND:Treatment outcomes for multidrug-resistant Mycobacterium Tuberculosis (MDRTB) are generally poor compared to drug sensitive disease. We sought to estimate treatment outcomes and identify risk factors associated with poor outcomes in patients with MDRTB. METHODOLOGY/PRINCIPAL FINDINGS:We performed a systematic search (to December 2008) to identify trials describing outcomes of patients treated for MDRTB. We pooled appropriate data to estimate WHO-defined outcomes at the end of treatment and follow-up. Where appropriate, pooled covariates were analyzed to identify factors associated with worse outcomes. Among articles identified, 36 met our inclusion criteria, representing 31 treatment programmes from 21 countries. In a pooled analysis, 62% [95% CI 57-67] of patients had successful outcomes, while 13% [9]-[17] defaulted, 11% [9]-[13] died, and 2% [1]-[4] were transferred out. Factors associated with worse outcome included male gender 0.61 (OR for successful outcome) [0.46-0.82], alcohol abuse 0.49 [0.39-0.63], low BMI 0.41[0.23-0.72], smear positivity at diagnosis 0.53 [0.31-0.91], fluoroquinolone resistance 0.45 [0.22-0.91] and the presence of an XDR resistance pattern 0.57 [0.41-0.80]. Factors associated with successful outcome were surgical intervention 1.91 [1.44-2.53], no previous treatment 1.42 [1.05-1.94], and fluoroquinolone use 2.20 [1.19-4.09]. CONCLUSIONS/SIGNIFICANCE:We have identified several factors associated with poor outcomes where interventions may be targeted. In addition, we have identified high rates of default, which likely contributes to the development and spread of MDRTB

Lipid Composition of the Human Eye: Are Red Blood Cells a Good Mirror of Retinal and Optic Nerve Fatty Acids?

International audienceBACKGROUND: The assessment of blood lipids is very frequent in clinical research as it is assumed to reflect the lipid composition of peripheral tissues. Even well accepted such relationships have never been clearly established. This is particularly true in ophthalmology where the use of blood lipids has become very common following recent data linking lipid intake to ocular health and disease. In the present study, we wanted to determine in humans whether a lipidomic approach based on red blood cells could reveal associations between circulating and tissue lipid profiles. To check if the analytical sensitivity may be of importance in such analyses, we have used a double approach for lipidomics. METHODOLOGY AND PRINCIPAL FINDINGS: Red blood cells, retinas and optic nerves were collected from 9 human donors. The lipidomic analyses on tissues consisted in gas chromatography and liquid chromatography coupled to an electrospray ionization source-mass spectrometer (LC-ESI-MS). Gas chromatography did not reveal any relevant association between circulating and ocular fatty acids except for arachidonic acid whose circulating amounts were positively associated with its levels in the retina and in the optic nerve. In contrast, several significant associations emerged from LC-ESI-MS analyses. Particularly, lipid entities in red blood cells were positively or negatively associated with representative pools of retinal docosahexaenoic acid (DHA), retinal very-long chain polyunsaturated fatty acids (VLC-PUFA) or optic nerve plasmalogens. CONCLUSIONS AND SIGNIFICANCE: LC-ESI-MS is more appropriate than gas chromatography for lipidomics on red blood cells, and further extrapolation to ocular lipids. The several individual lipid species we have identified are good candidates to represent circulating biomarkers of ocular lipids. However, further investigation is needed before considering them as indexes of disease risk and before using them in clinical studies on optic nerve neuropathies or retinal diseases displaying photoreceptors degeneration