Browsing by Author "Menzies, Dick"

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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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    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.
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    Treatment and outcomes in children with multidrug-resistant tuberculosis : a systematic review and individual patient data meta-analysis.
    (Public Library of Science, 2018-07-11) Harausz, Elizabeth P.; Garcia-Prats, Anthony J.; Law, Stephanie; Schaaf, H. Simon; Kredo, Tamara; Seddon, James A.; Menzies, Dick; Turkova, Anna; Achar, Jay; Amanullah, Farhana; Barry, Pennan; Becerra, Mercedes; Chan, Edward D.; Chan, Pei Chun; Chiotan, Domnica Ioana; Crossa, Aldo; Drobac, Peter C.; Fairlie, Lee; Falzon, Dennis; Flood, Jennifer; Gegia, Medea; Hicks, Robert M.; Isaakidis, Petros; Kadri, S. M.; Kampmann, Beate; Madhi, Shabir A.; Marais, Else; Mariandyshev, Andrei; Mendez-Echevarria, Ana; Moore, Brittany Kathryn; Nargiza, Parpieva; Ozere, Iveta; Padayatchi, Nesri; Ur-Rehman, Saleem; Rybak, Natasha; Santiago-Garcia, Begona; Shah, N. Sarita; Sharma, Sangeeta; Shim, Tae Sun; Skrahina, Alena; Soriano-Arandes, Antoni; Van Den Boom, Martin; Van Der Werf, Marieke J.; Van Der Werf, Tjip S.; Williams, Bhanu; Yablokova, Elena; Yim, Jae-Joon; Furin, Jennifer; Hesseling, Anneke C.
    Background: An estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children. Methods and findings: To inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%±19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%±48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15± 20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0±8.3, p = 0.041 and aOR 5.9, 95% CI 1.7±20.5, p = 0.007, respectively). These findings for high-dose isoniazid may have been affected by site effect, as the majority of patients came from Cape Town. Limitations of this study include the difficulty of estimating the treatment effects of individual drugs within multidrug regimens, only observational cohort studies were available for inclusion, and treatment decisions were based on the clinician's perception of illness, with resulting potential for bias. Conclusions: This study suggests that children respond favorably to MDR-TB treatment. The low success rate in children infected with HIV who did not receive ART during their MDR-TB treatment highlights the need for ART in these children. Our findings of individual drug effects on treatment outcome should be further evaluated.