Browsing by Author "Cobelens, Frank"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Effect of Xpert MTB/RIF on clinical outcomes in routine care settings : individual patient data meta-analysis
    (Elsevier, 2019-02) Di Tanna, Gian Luca; Khaki, Ali Raza; Theron, Grant; McCarthy, Kerrigan; Cox, Helen; Mupfumi, Lucy; Trajman, Anete; Mason, Peter; Bandason, Tsitsi; Durovni, Betina; Bara, Wilbert; Hoelscher, Michael; Clowes, Petra; Mangu, Chacha; Chanda, Duncan; Pym, Alexander; Mwaba, Peter; Cobelens, Frank; Nicol, Mark P.; Dheda, Keertan; Churchyard, Gavin; Fielding, Katherine; Metcalfe, John Z.
    Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I²<20% for the primary outcome). Interpretation Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact.
  • Thumbnail Image
    Item
    Translational research for tuberculosis elimination : priorities, challenges, and actions
    (Public Library of Science, 2016) Lienhardt, Christian; Lonnroth, Knut; Menzies, Dick; Balasegaram, Manica; Chakaya, Jeremiah; Cobelens, Frank; Cohn, Jennifer; Denkinger, Claudia M.; Evans, Thomas G.; Kallenius, Gunilla; Kaplan, Gilla; Kumar, Ajay M. V.; Matthiessen, Line; Mgone, Charles S.; Mizrahi, Valerie; Mukadi, Ya-diul; Nguyen, Viet Nhung; Nordstrom, Anders; Sizemore, Christine F.; Spigelman, Melvin; Squire, S. Bertel; Swaminathan, Soumya; Van Helden, Paul D.; Zumla, Alimuddin; Weyer, Karin; Weil, Diana; Raviglione, Mario
    Summary Points: • The WHO End TB Strategy, endorsed by the World Health Assembly in May 2014, has the ambitious goal of ending the global tuberculosis (TB) epidemic by 2035, with targets of a 95% decline in deaths due to TB (compared with 2015) and a 90% reduction in incidence of TB to ten cases/100,000 or less and no TB-affected household experiencing catastrophic costs due to TB. • Achieving this goal will only be possible through the development and rapid uptake of new tools, including rapid point-of-care diagnostics, safe and shorter treatment of latent TB infection and disease, and an efficacious TB vaccine, combined with efficient health systems and care provision, and actions on the social determinants of TB. • Research for TB elimination requires an intensification of efforts across a continuum from fundamental research to clinical, epidemiological, implementation, health system, and social science research. • Enhancing research along the full spectrum, from basic to implementation, and strengthening research capacity, particularly in low- and middle-income countries severely affected by the TB epidemics, is crucial for TB elimination. • The creation of a research-enabling environment that fosters and rewards high-quality research requires a broad-based, concerted effort by national governments and international donors to develop and promote TB research and research capacity at the country level and the effective engagement of all stakeholders.