Characteristics and Early Outcomes of Patients With Xpert MTB/RIF-Negative Pulmonary Tuberculosis Diagnosed During Screening Before Antiretroviral Therapy

Comparison of the characteristics of HIV-infected patients with Xpert-positive and Xpert-negative tuberculosis and relationship of Xpert status with subsequent clinical and programmatic outcomes

Delays in starting antiretroviral therapy in patients with HIV-associated tuberculosis accessing non-integrated clinical services in a South African township

BACKGROUND: Delays in the initiation of antiretroviral therapy (ART) in patients with HIV-associated tuberculosis (TB) are associated with increased mortality risk. We examined the timing of ART among patients receiving care provided by non-integrated TB and ART services in Cape Town, South Africa. METHODS: In an observational cohort study, we determined the overall time delay between starting treatment for TB and starting ART in patients treated in Gugulethu township between 2002 and 2008. For patients referred from TB clinics to the separate ART clinic, we quantified and identified risk factors associated with the two component delays between starting TB treatment, enrolment in the ART clinic and subsequent initiation of ART. RESULTS: Among 893 TB patients studied (median CD4 count, 81 cells/μL), the delay between starting TB treatment and starting ART was prolonged (median, 95 days; IQR = 49-155). Delays were shorter in more recent calendar periods and among those with lower CD4 cell counts. However, the median delay was almost three-fold longer for patients referred from separate TB clinics compared to patients whose TB was diagnosed in the ART clinic (116 days versus 41 days, respectively; P < 0.001). In the most recent calendar period, the proportions of patients with CD4 cell counts < 50 cells/μL who started ART within 4 weeks of TB diagnosis were 11.1% for patients referred from TB clinics compared to 54.6% of patients with TB diagnosed in the ART service (P < 0.001). CONCLUSIONS: Delays in starting ART were prolonged, especially for patients referred from separate TB clinics. Non-integration of TB and ART services is likely to be a substantial obstacle to timely initiation of ART

Screening for HIV-Associated Tuberculosis and Rifampicin Resistance before Antiretroviral Therapy Using the Xpert MTB/RIF Assay: A Prospective Study

In a prospective study, Stephen Lawn and colleagues find that pre-ART screening with Xpert MTB/RIF increased tuberculosis case detection by 45% compared to smear microscopy in HIV-positive patients at high risk of TB risk. AE competing interests must also pull through to the proof. “The Academic Editor, Madhukar Pai, declares that he consults for the Bill & Melinda Gates Foundation (BMGF). The BMGF supported FIND which was involved in the development of the Xpert MTB/RIF assay. He also co-chairs the Stop TB Partnership's New Diagnostics Working Group that was involved in the WHO endorsement of the Xpert assay.” Linked: Scott pmed.1001061; Evans pmed.1001064; Dowdy pmed.100106

Failure time and microcrack nucleation

The failure time of samples of heterogeneous materials (wood, fiberglass) is studied as a function of the applied stress. It is shown that in these materials the failure time is predicted with a good accuracy by a model of microcrack nucleation proposed by Pomeau. It is also shown that the crack growth process presents critical features when the failure time is approached.Comment: 13 pages, 4 figures, submitted to Europhysics Letter

Six-Month Mortality among HIV-Infected Adults Presenting for Antiretroviral Therapy with Unexplained Weight Loss, Chronic Fever or Chronic Diarrhea in Malawi.

In sub-Saharan Africa, early mortality is high following initiation of antiretroviral therapy (ART). We investigated 6-month outcomes and factors associated with mortality in HIV-infected adults being assessed for ART initiation and presenting with weight loss, chronic fever or diarrhea, and with negative TB sputum microscopy

Tuberculosis Incidence Rates during 8 Years of Follow-Up of an Antiretroviral Treatment Cohort in South Africa: Comparison with Rates in the Community

BACKGROUND: Although antiretroviral therapy (ART) is known to be associated with time-dependent reductions in tuberculosis (TB) incidence, the long-term impact of ART on incidence remains imprecisely defined due to limited duration of follow-up and incomplete CD4 cell count recovery in existing studies. We determined TB incidence in a South African ART cohort with up to 8 years of follow-up and stratified rates according to CD4 cell count recovery. We compared these rates with those of HIV-uninfected individuals living in the same community. METHODOLOGY/PRINCIPAL FINDINGS: Prospectively collected clinical data on patients receiving ART in a community-based cohort in Cape Town were analysed. 1544 patients with a median follow-up of 5.0 years (IQR 2.4-5.8) were included in the analysis. 484 episodes of incident TB (73.6% culture-confirmed) were diagnosed in 424 patients during 6506 person-years (PYs) of follow-up. The TB incidence rate during the first year of ART was 12.4 (95% CI 10.8-14.4) cases/100PYs and decreased to 4.92 (95% CI 3.64-8.62) cases/100PYs between 5 and 8 years of ART. During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500, 501-700 and ≥700 cells/µL, TB incidence rates (95% CI) were 25.5 (21.6-30.3), 11.2 (9.4-13.5), 7.9 (6.4-9.7), 5.0 (3.9-6.6), 5.1 (3.8-6.8), 4.1 (3.1-5.4) and 2.7 (1.7-4.5) cases/100PYs, respectively. Overall, 75% (95% CI 70.9-78.8) of TB episodes were recurrent cases. Updated CD4 cell count and viral load measurements were independently associated with long-term TB risk. TB rates during person-time accrued in the highest CD4 cell count stratum (>700 cells/µL) were 4.4-fold higher that the rate in HIV uninfected individuals living in the same community (2.7 versus 0.62 cases/100PYs; 95%CI 0.58-0.65). CONCLUSIONS/SIGNIFICANCE: TB rates during long-term ART remained substantially greater than rates in the local HIV uninfected populations regardless of duration of ART or attainment of CD4 cell counts exceeding 700 cells/µL

Identification of losses to follow-up in a community-based antiretroviral therapy clinic in South Africa using a computerized pharmacy tracking system

BACKGROUND: High rates of loss to follow-up (LTFU) are undermining rapidly expanding antiretroviral treatment (ART) services in sub-Saharan Africa. The intelligent dispensing of ART (iDART) is an open-source electronic pharmacy system that provides an efficient means of generating lists of patients who have failed to pick-up medication. We determined the duration of pharmacy delay that optimally identified true LTFU. METHODS: We conducted a retrospective cross-sectional study of a community-based ART cohort in Cape Town, South Africa. We used iDART to identify groups of patients known to be still enrolled in the cohort on the 1st of April 2008 that had failed to pick-up medication for periods of ≥ 6, ≥ 12, ≥ 18 and ≥ 24 weeks. We defined true LTFU as confirmed failure to pick up medication for 3 months since last attendance. We then assessed short-term and long-term outcomes using a prospectively maintained database and patient records. RESULTS: On the date of the survey, 2548 patients were registered as receiving ART but of these 85 patients (3.3%) were found to be true LTFU. The numbers of individuals (proportion of the cohort) identified by iDART as having failed to collect medication for periods of ≥ 6, ≥ 12, ≥ 18 and ≥ 24 weeks were 560 (22%), 194 (8%), 117 (5%) and 80 (3%), respectively. The sensitivities of these pharmacy delays for detecting true LTFU were 100%, 100%, 62.4% and 47.1%, respectively. The corresponding specificities were 80.7%, 95.6%, 97.4% and 98.4%. Thus, the optimal delay was ≥ 12 weeks since last attendance at this clinic (equivalent to 8 weeks since medication ran out). Pharmacy delays were also found to be significantly associated with LTFU and death one year later. CONCLUSIONS: The iDART electronic pharmacy system can be used to detect patients potentially LTFU and who require recall. Using a short a cut-off period was too non-specific for LTFU and would require the tracing of very large numbers of patients. Conversely prolonged delays were too insensitive. Of the periods assessed, a ≥ 12 weeks delay appeared optimal. This system requires prospective evaluation to further refine its utility

Dynamical stability of the crack front line

Dynamical stability of the crack front line that propagates between two plates is studied numerically using the simple two-dimensional mass-spring model. It is demonstrated that the straight front line is unstable for low speed while it becomes stable for high speed. For the uniform model, the roughness exponent in the slower speed region is fairly constant around 0.4 and there seems to be a rough-smooth transition at a certain speed. For the inhomogeneous case with quenched randomness, the transition is gradual.Comment: 14 pages, 7 figure