Browsing by Author "Pai, Madhukar"

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    Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes : an individual patient data meta-analysis of 9,153 patients
    (Public Library of Science, 2012-08-28) Ahuja, Shama D.; Ashkin, David; Avendano, Monika; Banerjee, Rita; Bauer, Melissa; Bayona, Jamie N.; Becerra, Mercedes C.; Benedetti, Andrea; Burgos, Marcos; Centis, Rosella; Chan, Eward D.; Chiang, Chen-Yuan; Cox, Helen; D'Ambrosio, Lia; DeRiemer, Kathy; Dung, Nguyen Huy; Enarson, Donald; Falzon, Dennis; Flanagan, Katherine; Flood, Jennifer; Garcia-Garcia, Maria L.; Ghandi, Neel; Granich, Reuben M.; Hollm-Delgado, Maria G.; Holtz, Timothy H.; Iseman, Michael D.; Jarlsberg, Leah G.; Keshavjee, Salmaan; Kim, Hye-Ryoun; Koh, Won-Jung; Lancaster, Joey; Lange,Christophe; Lange, Wiel C. M. de; Leimane, Vaira; Leung, Chi Chiu; Li, Jiehui; Menzies, Dick; Migliori, Giovanni B.; Mishustin, Sergey P.; Mitnick, Carole D.; Narita, Masa; O'Riordan, Philly; Pai, Madhukar; Palmero, Domingo; Park, Seung-kyu; Pasvol, Geoffrey; Pena, Jose; Perez-Guzman, Carlos; Quelapio, Maria I. D.; Ponce-De-Leon, Alfredo; Riekstina, Vija; Robert, Jerome; Royce, Sarah; Schaaf, H. Simon; Seung, Kwonjune J.; Shah, Lena; Shim, Tae Sun; Shin, Sonya S.; Shiraishi, Yuji; Sifuentes-Osornio, Jose; Sotgiu, Giovanni; Strand, Matthew J.; Tabarsi, Payam; Tupasi, Thelma E.; Altena, Robert van; Van der Walt, Martie; Werf, Tjip S. van der; Vargas, Mario H.; Viiklepp, Pirett; Westenhouse, Janice; Yew, Wing Wai; Yim, Jae-Joon
    Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1–6.0]), ofloxacin (aOR: 2.5 [1.6–3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3–2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3–3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7–4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7–4.3]), ofloxacin (aOR: 2.3 [1.3–3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4–2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9–3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4–6.0]). Conclusions: In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.
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    Propensity score-based approaches to confounding by indication in individual patient data meta-analysis: non-standardized treatment for multidrug resistant tuberculosis
    (Public Library of Science, 2016) Fox, Gregory J.; Benedetti, Andrea; Mitnick, Carole D.; Pai, Madhukar; Menzies, Dick; The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB
    Background: In the absence of randomized clinical trials, meta-analysis of individual patient data (IPD) from observational studies may provide the most accurate effect estimates for an intervention. However, confounding by indication remains an important concern that can be addressed by incorporating individual patient covariates in different ways. We compared different analytic approaches to account for confounding in IPD from patients treated for multi-drug resistant tuberculosis (MDR-TB). Methods: Two antibiotic classes were evaluated, fluoroquinolones—considered the cornerstone of effective MDR-TB treatment—and macrolides, which are known to be safe, yet are ineffective in vitro. The primary outcome was treatment success against treatment failure, relapse or death. Effect estimates were obtained using multivariable and propensity-score based approaches. Results: Fluoroquinolone antibiotics were used in 28 included studies, within which 6,612 patients received a fluoroquinolone and 723 patients did not. Macrolides were used in 15 included studies, within which 459 patients received this class of antibiotics and 3,670 did not. Both standard multivariable regression and propensity score-based methods resulted in similar effect estimates for early and late generation fluoroquinolones, while macrolide antibiotics use was associated with reduced treatment success. Conclusions: In this individual patient data meta-analysis, standard multivariable and propensity-score based methods of adjusting for individual patient covariates for observational studies yielded produced similar effect estimates. Even when adjustment is made for potential confounding, interpretation of adjusted estimates must still consider the potential for residual bias.
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    Xpert MTB/RIF and Xpert MTB/RIF Ultra for pulmonary tuberculosis and rifampicin resistance in adults
    (John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration, 2019) Horne, David J.; Kohli, Mikashmi; Zifodya, Jerry S.; Schiller, Ian; Dendukuri, Nandini; Tollefson, Deanna; Schumache, Samuel G.; Ochodo, Eleanor A.; Pai, Madhukar; Steingart, Karen R.
    Background: Xpert MTB/RIF (Xpert MTB/RIF) and Xpert MTB/RIF Ultra (Xpert Ultra), the newest version, are the only World Health Organization (WHO)- recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in persons with signs and symptoms of tuberculosis, at lower health system levels. A previous Cochrane Review found Xpert MTB/RIF sensitive and specific for tuberculosis (Steingart 2014). Since the previous review, new studies have been published. We performed a review update for an upcoming WHO policy review. Objectives: To determine diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for tuberculosis in adults with presumptive pulmonary tuberculosis (PTB) and for rifampicin resistance in adults with presumptive rifampicin-resistant tuberculosis. Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, to 11 October 2018, without language restriction. Selection criteria: Randomized trials, cross-sectional, and cohort studies using respiratory specimens that evaluated Xpert MTB/RIF, Xpert Ultra, or both against the reference standard, culture for tuberculosis and culture-based drug susceptibility testing or MTBDRplus for rifampicin resistance. Data collection and analysis: Four review authors independently extracted data using a standardized form. When possible, we also extracted data by smear and HIV status. We assessed study quality using QUADAS-2 and performed meta-analyses to estimate pooled sensitivity and specificity separately for tuberculosis and rifampicin resistance. We investigated potential sources of heterogeneity. Most analyses used a bivariate randome Kects model. For tuberculosis detection, we first estimated accuracy using all included studies and then only the subset of studies where participants were unselected, i.e. not selected based on prior microscopy testing. Main results: We identified in total 95 studies (77 new studies since the previous review): 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert MTB/RIF and Xpert Ultra on the same participant specimen.