Browsing by Author "Chanda, Duncan"

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    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.
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    A living WHO guideline on drugs for covid-19
    (2022-09) Agarwal, Arnav; Rochwerg, Bram; Lamontagne, François; Siemieniuk, Reed AC; Agoritsas, Thomas; Askie, Lisa; Lytvyn, Lyubov; Leo, Yee-Sin; Macdonald, Helen; Zeng, Linan; Amin, Wagdy; Barragan, Fabian A Jaimes; Bausch, Frederique J.; Burhan, Erlina; Calfee, Carolyn S.; Cecconi, Maurizio; Chanda, Duncan; Dat, Vu Quoc; De Sutter, An; Du, Bin; Freedman, Stephen; Geduld, Heike; Gee, Patrick; Gotte, Matthias; Harley, Nerina; Hashmi, Madiha; Hunt, Beverley; Jehan, Fyezah; Kabra, Sushil K.; Kanda, Seema; Kim, Yae-Jean; Kissoon, Niranjan; Krishna, Sanjeev; Kuppalli, Krutika; Kwizera, Arthur; Castro-Rial, Marta Lado; Lisboa, Thiago; Lodha, Rakesh; Mahaka, Imelda; Manai, Hela; Mino, Greta; Nsutebu, Emmanuel; Preller, Jacobus; Pshenichnaya, Natalia; Qadir, Nida; Relan, Pryanka; Sabzwari, Saniya; Sarin, Rohit; Shankar-Hari, Manu; Sharland, Michael; Shen, Yinzhong; Ranganathan, Shalini S.; Souza, Joao P.; Stegemann, Miriam; Swanstrom, Ronald; Ugarte, Sebastian; Uyeki, Tim; Venkatapuram, Sridhar; Vuyiseka, Dubula; Wijewickrama, Ananda; Tran, Lien; Zeraatkar, Dena; Bartoszko, Jessica J.; Ge, Long; Brignardello-Petersen, Romina; Owen, Andrew; Guyatt, Gordon; Diaz, Janet; Kawano-Dourado, Leticia; Jacobs, Michael; Vandvik, Per Olav
    This living guideline by Arnav Agarwal and colleagues (BMJ 2020;370:m3379, doi:10.1136/bmj.m3379) was last updated on 22 April 2022, but the infographic contained two dosing errors: the dose of ritonavir with renal failure should have read 100 mg, not 50 mg; and the suggested regimen for remdesivir should have been 3 days, not 5-10 days. The infographic has now been corrected.
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    Point of care Xpert MTB/RIF versus smear microscopy for tuberculosis diagnosis in southern African primary care clinics : a multicentre economic evaluation
    (Elsevier, 2019-06-01) Pooran, Anil; Theron, Grant; Zijenah, Lynn; Chanda, Duncan; Clowes, Petra; Mwenge, Lawrence; Mutenherwa, Farirai; Lecesse, Paul; Metcalfe, John; Sohn, Hojoon; Hoelscher, Michael; Pym, Alex; Peter, Jonny; Dowdy, David; Dheda, Keertan
    Background: Rapid on-site diagnosis facilitates tuberculosis control. Performing Xpert MTB/RIF (Xpert) at point of care is feasible, even when performed by minimally trained health-care workers, and when compared with point-of-care smear microscopy, reduces time to diagnosis and pretreatment loss to follow-up. However, whether Xpert is cost-effective at point of care remains unclear. Methods: We empirically collected cost (US$, 2014) and clinical outcome data from participants presenting to primary health-care facilities in four African countries (South Africa, Zambia, Zimbabwe, and Tanzania) during the TB-NEAT trial. Costs were determined using an bottom-up ingredients approach. Effectiveness measures from the trial included number of cases diagnosed, initiated on treatment, and completing treatment. The primary outcome was the incremental cost-effectiveness of point-of-care Xpert relative to smear microscopy. The study was performed from the perspective of the health-care provider. Findings: Using data from 1502 patients, we calculated that the mean Xpert unit cost was lower when performed at a centralised laboratory (Lab Xpert) rather than at point of care ($23·00 [95% CI 22·12–23·88] vs $28·03 [26·19–29·87]). Per 1000 patients screened, and relative to smear microscopy, point-of-care Xpert cost an additional $35 529 (27 054–40 025) and was associated with an additional 24·3 treatment initiations ([–20·0 to 68·5]; $1464 per treatment), 63·4 same-day treatment initiations ([27·3–99·4]; $511 per same-day treatment), and 29·4 treatment completions ([–6·9 to 65·6]; $1211 per completion). Xpert costs were most sensitive to test volume, whereas incremental outcomes were most sensitive to the number of patients initiating and completing treatment. The probability of point-of-care Xpert being cost-effective was 90% at a willingness to pay of $3820 per treatment completion. Interpretation: In southern Africa, although point-of-care Xpert unit cost is higher than Lab Xpert, it is likely to offer good value for money relative to smear microscopy. With the current availability of point-of-care nucleic acid amplification platforms (eg, Xpert Edge), these data inform much needed investment and resource allocation strategies in tuberculosis endemic settings.