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1. Early onset metastatic colorectal cancer patients as a distinctive clinical and molecular phenomenon: Clinical Studies

Author

Pretta, Andrea, Ziranu, Pina, Perissinotto, Eleonora, Ghelardi, Filippo, Marmorino, Federica, Giampieri, Riccardo, Puci, Mariangela, De Grandis, Maria Caterina, Lai, Eleonora, Nasca, Vincenzo, Ciraci, Paolo, Puzzoni, Marco, Cerma, Krisida, Sciortino, Carolina, Taravella, Ada, Pretta, Gianluca, Giuliani, Lorenzo, Damonte, Camilla, Pusceddu, Valeria, Sotgiu, Giovanni, Berardi, Rossana, Lonardi, Sara, Bergamo, Francesca, Pietrantonio, Filippo, Cremolini, Chiara, and Scartozzi, Mario

Published
2025
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12. Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis.

Author

Huerga, Helena, Villalba, Julian, Grandjean, Louis, Sotgiu, Giovanni, Egere, Uzochukwu, Singh, Sarman, Zhu, Limei, Lienhardt, Christian, Denholm, Justin, Seddon, James, Whalen, Christopher, García-Basteiro, Alberto, Triasih, Rina, Chen, Cheng, Singh, Jitendra, Huang, Li-Min, Sharma, Surendra, Hannoun, Djohar, Del Corral, Helena, Mandalakas, Anna, Malone, LaShaunda, Ling, Du-Lin, Kritski, Afrânio, Stein, Catherine, Vashishtha, Richa, Boulahbal, Fadila, Fang, Chi-Tai, Boom, W, Netto, Eduardo, Lemos, Antonio, Hesseling, Anneke, Kay, Alexander, Jones-López, Edward, Horsburgh, C, Lange, Christoph, Andrews, Jason, Martinez, Leonardo, Cords, Olivia, Liu, Qiao, Acuna-Villaorduna, Carlos, Bonnet, Maryline, Fox, Greg, Carvalho, Anna, Chan, Pei-Chun, Croda, Julio, Hill, Philip, Lopez-Varela, Elisa, Donkor, Simon, Fielding, Katherine, Graham, Stephen, Espinal, Marcos, Kampmann, Beate, and Reingold, Arthur

Subjects
Adolescent, Adult, Aged, BCG Vaccine, Child, Child, Preschool, Humans, Infant, Infant, Newborn, Retrospective Studies, Tuberculosis, Tuberculosis, Pulmonary, Vaccination
Abstract

BACKGROUND: BCG vaccines are given to more than 100 million children every year, but there is considerable debate regarding the effectiveness of BCG vaccination in preventing tuberculosis and death, particularly among older children and adults. We therefore aimed to investigate the age-specific impact of infant BCG vaccination on tuberculosis (pulmonary and extrapulmonary) development and mortality. METHODS: In this systematic review and individual participant data meta-analysis, we searched MEDLINE, Web of Science, BIOSIS, and Embase without language restrictions for case-contact cohort studies of tuberculosis contacts published between Jan 1, 1998, and April 7, 2018. Search terms included mycobacterium tuberculosis, TB, tuberculosis, and contact. We excluded cohort studies that did not provide information on BCG vaccination or were done in countries that did not recommend BCG vaccination at birth. Individual-level participant data for a prespecified list of variables, including the characteristics of the exposed participant (contact), the index case, and the environment, were requested from authors of all eligible studies. Our primary outcome was a composite of prevalent (diagnosed at or within 90 days of baseline) and incident (diagnosed more than 90 days after baseline) tuberculosis in contacts exposed to tuberculosis. Secondary outcomes were pulmonary tuberculosis, extrapulmonary tuberculosis, and mortality. We derived adjusted odds ratios (aORs) using mixed-effects, binary, multivariable logistic regression analyses with study-level random effects, adjusting for the variable of interest, baseline age, sex, previous tuberculosis, and whether data were collected prospectively or retrospectively. We stratified our results by contact age and Mycobacterium tuberculosis infection status. This study is registered with PROSPERO, CRD42020180512. FINDINGS: We identified 14 927 original records from our database searches. We included participant-level data from 26 cohort studies done in 17 countries in our meta-analysis. Among 68 552 participants, 1782 (2·6%) developed tuberculosis (1309 [2·6%] of 49 686 BCG-vaccinated participants vs 473 [2·5%] of 18 866 unvaccinated participants). The overall effectiveness of BCG vaccination against all tuberculosis was 18% (aOR 0·82, 95% CI 0·74-0·91). When stratified by age, BCG vaccination only significantly protected against all tuberculosis in children younger than 5 years (aOR 0·63, 95% CI 0·49-0·81). Among contacts with a positive tuberculin skin test or IFNγ release assay, BCG vaccination significantly protected against tuberculosis among all participants (aOR 0·81, 95% CI 0·69-0·96), participants younger than 5 years (0·68, 0·47-0·97), and participants aged 5-9 years (0·62, 0·38-0·99). There was no protective effect among those with negative tests, unless they were younger than 5 years (0·54, 0·32-0·90). 14 cohorts reported on whether tuberculosis was pulmonary or extrapulmonary (n=57 421). BCG vaccination significantly protected against pulmonary tuberculosis among all participants (916 [2·2%] in 41 119 vaccinated participants vs 334 [2·1%] in 16 161 unvaccinated participants; aOR 0·81, 0·70-0·94) but not against extrapulmonary tuberculosis (106 [0·3%] in 40 318 vaccinated participants vs 38 [0·2%] in 15 865 unvaccinated participants; 0·96, 0·65-1·41). In the four studies with mortality data, BCG vaccination was significantly protective against death (0·25, 0·13-0·49). INTERPRETATION: Our results suggest that BCG vaccination at birth is effective at preventing tuberculosis in young children but is ineffective in adolescents and adults. Immunoprotection therefore needs to be boosted in older populations. FUNDING: National Institutes of Health.

Published
2022

16. Modeling Treatment Effect Modification in Multidrug-Resistant Tuberculosis in an Individual Patient Data Meta-Analysis

Author

Liu, Yan, Schnitzer, Mireille, Wang, Guanbo, Kennedy, Edward, Viiklepp, Piret, Vargas, Mario H., Sotgiu, Giovanni, Menzies, Dick, and Benedetti, Andrea

Subjects
Statistics - Methodology
Abstract

Effect modification occurs while the effect of the treatment is not homogeneous across the different strata of patient characteristics. When the effect of treatment may vary from individual to individual, precision medicine can be improved by identifying patient covariates to estimate the size and direction of the effect at the individual level. However, this task is statistically challenging and typically requires large amounts of data. Investigators may be interested in using the individual patient data (IPD) from multiple studies to estimate these treatment effect models. Our data arise from a systematic review of observational studies contrasting different treatments for multidrug-resistant tuberculosis (MDR-TB), where multiple antimicrobial agents are taken concurrently to cure the infection. We propose a marginal structural model (MSM) for effect modification by different patient characteristics and co-medications in a meta-analysis of observational IPD. We develop, evaluate, and apply a targeted maximum likelihood estimator (TMLE) for the doubly robust estimation of the parameters of the proposed MSM in this context. In particular, we allow for differential availability of treatments across studies, measured confounding within and across studies, and random effects by study., Comment: 16 pages, 1 table, 5 figures

Published
2021

20. Tuberculosis, Epidemiology of

Author

Sotgiu, Giovanni, Zignol, Matteo, Raviglione, Mario C., Spangler, Matthew L., Section editor, Meyers, Robert A., Editor-in-Chief, and Shulman, Lester M, editor

Published
2023
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27. Reply to Chang and Yew

Author

Sotgiu, Giovanni, Migliori, Giovanni Battista, Menzies, Dick, Mase, Sundari, Chorba, Terence, Seaworth, Barbara, and Nahid, Payam

Subjects
Centers for Disease Control and Prevention, U.S., Humans, Tuberculosis, Multidrug-Resistant, United States, Medical and Health Sciences, Respiratory System
Published
2020

28. The risk of tuberculosis in children after close exposure: a systematic review and individual-participant meta-analysis

Author

Martinez, Leonardo, Cords, Olivia, Horsburgh, C Robert, Andrews, Jason R, Consortium, Pediatric TB Contact Studies, Acuna-Villaorduna, Carlos, Ahuja, Shama Desai, Altet, Neus, Augusto, Orvalho, Baliashvili, Davit, Basu, Sanjay, Becerra, Mercedes, Bonnet, Maryline, Boom, W Henry, Borgdorff, Martien, Boulahbal, Fadila, Carvalho, Anna Cristina C, Cayla, Joan A, Chakhaia, Tsira, Chan, Pei-Chun, Cohen, Ted, Croda, Julio, Datta, Sumona, del Corral, Helena, Denholm, Justin T, Dietze, Reynaldo, Dobler, Claudia C, Donkor, Simon, Egere, Uzochukwu, Ellner, Jerrold J, Espinal, Marcos, Evans, Carlton A, Fang, Chi-Tai, Fielding, Katherine, Fox, Greg J, García, Luis F, García-Basteiro, Alberto L, Geis, Steffen, Graham, Stephen M, Grandjean, Louis, Hannoun, Djohar, Hatherill, Mark, Hauri, Anja M, Hesseling, Anneke C, Hill, Philip C, Huang, Li-Min, Huerga, Helena, Hussain, Rabia, Jarlsberg, Leah, Jones-López, Edward C, Kato, Seiya, Kato-Maeda, Midori, Kampmann, Beate, Kirchner, H Lester, Kritski, Afrânio, Lange, Christoph, Lee, Chih-Hsin, Lee, Li-Na, Lee, Meng-Rui, Lemos, Antonio Carlos, Lienhardt, Christian, Ling, Du-Lin, Liu, Qiao, Lo, Nathan C, Long, Richard, Lopez-Varela, Elisa, Lu, Peng, Magee, Matthew, Malone, LaShaunda L, Mandalakas, Anna M, Martinson, Neil A, Mazahir, Rufaida, Murray, Megan B, Netto, Eduardo Martins, Otero, Larissa, Parsonnet, Julie, Reingold, Arthur, Schaaf, H Simon, Seddon, James A, Sharma, Surendra, Singh, Jitendra, Singh, Sarman, Sloot, Rosa, Sotgiu, Giovanni, Stein, Catherine M, Iqbal, Najeeha Talat, Triasih, Rina, Trieu, Lisa, van der Loeff, Maarten F Schim, Van der Stuyft, Patrick, van Schalkwyk, Cari, Vashishtha, Richa, Verhagen, Lilly M, Villalba, Julian A, Wang, Jann-Yuan, Whalen, Christopher C, Yoshiyama, Takashi, Zar, Heather J, Zellweger, Jean-Pierre, and Zhu, Limei

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Health Sciences, Infectious Diseases, Rare Diseases, Prevention, Pediatric, Tuberculosis, Emerging Infectious Diseases, Infection, Good Health and Well Being, Adolescent, Age Factors, Child, Child, Preschool, Contact Tracing, Disease Transmission, Infectious, Family Characteristics, Female, Global Health, Humans, Incidence, Male, Mycobacterium tuberculosis, Risk Assessment, Sex Factors, Tuberculosis, Pulmonary, Pediatric TB Contact Studies Consortium, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundTens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood.MethodsIn this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protocol is registered with PROSPERO (CRD42018087022).FindingsIn total, study groups from 46 cohort studies in 34 countries-29 (63%) prospective studies and 17 (37%) retrospective-agreed to share their data and were included in the final analysis. 137 647 tuberculosis-exposed children were evaluated at baseline and 130 512 children were followed for 429 538 person-years, during which 1299 prevalent and 999 incident tuberculosis cases were diagnosed. Children not receiving preventive therapy with a positive result for tuberculosis infection had significantly higher 2-year cumulative tuberculosis incidence than children with a negative result for tuberculosis infection, and this incidence was greatest among children below 5 years of age (19·0% [95% CI 8·4-37·4]). The effectiveness of preventive therapy was 63% (adjusted HR 0·37 [95% CI 0·30-0·47]) among all exposed children, and 91% (adjusted HR 0·09 [0·05-0·15]) among those with a positive result for tuberculosis infection. Among all children

Published
2020

31. Impact of COVID-19 on diagnosis of tuberculosis, multidrug-resistant tuberculosis, and on mortality in 11 countries in Europe, Northern America, and Australia. A Global Tuberculosis Network study

Author

Nalunjogi, Joanitah, Mucching-Toscano, Sergio, Sibomana, Jean Pierre, Centis, Rosella, D'Ambrosio, Lia, Alffenaar, Jan-Willem, Denholm, Justin, Blanc, François-Xavier, Borisov, Sergey, Danila, Edvardas, Duarte, Raquel, García-García, José-María, Goletti, Delia, Ong, Catherine W.M., Rendon, Adrian, Thomas, Tania A., Tiberi, Simon, van den Boom, Martin, Sotgiu, Giovanni, and Migliori, Giovanni Battista

Published
2023
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32. Interventional pulmonology techniques in lung transplantation

Author

Mondoni, Michele, Rinaldo, Rocco Francesco, Solidoro, Paolo, Di Marco, Fabiano, Patrucco, Filippo, Pavesi, Stefano, Baccelli, Andrea, Carlucci, Paolo, Radovanovic, Dejan, Santus, Pierachille, Raimondi, Federico, Vedovati, Sergio, Morlacchi, Letizia Corinna, Blasi, Francesco, Sotgiu, Giovanni, and Centanni, Stefano

Published
2023
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33. Predictive performance of interferon-gamma release assays and the tuberculin skin test for incident tuberculosis: an individual participant data meta-analysis

Author

Hamada, Yohhei, Gupta, Rishi K., Quartagno, Matteo, Izzard, Abbie, Acuna-Villaorduna, Carlos, Altet, Neus, Diel, Roland, Dominguez, Jose, Floyd, Sian, Gupta, Amita, Huerga, Helena, Jones-López, Edward C., Kinikar, Aarti, Lange, Christoph, van Leth, Frank, Liu, Qiao, Lu, Wei, Lu, Peng, Rueda, Irene Latorre, Martinez, Leonardo, Mbandi, Stanley Kimbung, Muñoz, Laura, Padilla, Elisabeth Sánchez, Paradkar, Mandar, Scriba, Thomas, Sester, Martina, Shanaube, Kwame, Sharma, Surendra K., Sloot, Rosa, Sotgiu, Giovanni, Thiruvengadam, Kannan, Vashishtha, Richa, Abubakar, Ibrahim, and Rangaka, Molebogeng X.

Published
2023
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34. Bacterial Patterns and Empiric Antibiotic Use in COPD Patients With Community-Acquired Pneumonia

Author

Aruj, Patricia Karina, Attorri, Silvia, Barimboim, Enrique, Caeiro, Juan Pablo, Garzón, María I., Cambursano, Victor Hugo, Ceccato, Adrian, Chertcoff, Julio, Lascar, Florencia, Tulio, Fernando Di, Díaz, Ariel Cordon, Vedia, Lautaro de, Ganaha, Maria Cristina, Lambert, Sandra, Lopardo, Gustavo, Luna, Carlos M., Malberti, Alessio Gerardo, Morcillo, Nora, Tartara, Silvina, Pensotti, Claudia, Pereyra, Betiana, Scapellato, Pablo Gustavo, Stagnaro, Juan Pablo, Shah, Sonali, Lötsch, Felix, Thalhammer, Florian, Anseeuw, Kurt, Francois, Camille A., Braeckel, Eva Van, Vincent, Jean Louis, Djimon, Marcel Zannou, Bashi, Jules, Dodo, Roger, Nouér, Simone Aranha, Chipev, Peter, Encheva, Milena, Miteva, Darina, Petkova, Diana, Balkissou, Adamou Dodo, Pefura Yone, Eric Walter, Mbatchou Ngahane, Bertrand Hugo, Shen, Ning, Xu, Jin-fu, Bustamante Rico, Carlos Andres, Buitrago, Ricardo, Pereira Paternina, Fernando Jose, Kayembe Ntumba, Jean-Marie, Carevic, Vesna Vladic, Jakopovic, Marko, Jankovic, Mateja, Matkovic, Zinka, Mitrecic, Ivan, Bouchy Jacobsson, Marie-Laure, Christensen, Anette Bro, Bødtger, Uffe, Meyer, Christian Niels, Jensen, Andreas Vestergaard, Baunbæk-knudsen, Gertrud, Petersen, Pelle Trier, Andersen, Stine, Abd El-Wahhab, Ibrahim El-Said, Morsy, Nesreen Elsayed, Shafiek, Hanaa, Sobh, Eman, Abdulsemed, Kedir Abdella, Bertrand, Fabrice, Brun-Buisson, Christian, Montmollin, Etienne de, Fartoukh, Muriel, Messika, Jonathan, Tattevin, Pierre, Khoury, Abdo, Ebruke, Bernard, Dreher, Michael, Kolditz, Martin, Meisinger, Matthias, Pletz, Mathias W., Hagel, Stefan, Rupp, Jan, Schaberg, Tom, Spielmanns, Marc, Creutz, Petra, Suttorp, Norton, Siaw-Lartey, Beatrice, Dimakou, Katerina, Gaga, Mina, Papapetrou, Dimosthenis, Tsigou, Evdoxia, Ampazis, Dimitrios, Kaimakamis, Evangelos, Bhatia, Mohit, Dhar, Raja, D'Souza, George, Garg, Rajiv, Koul, Parvaiz A., Mahesh, P.A., Jayaraj, B.S., Narayan, Kiran Vishnu, Udnur, Hirennappa B., Krishnamurthy, Shashi Bhaskara, Kant, Surya, Swarnakar, Rajesh, Limaye, Sneha, Salvi, Sundeep, Golshani, Keihan, Keatings, Vera M., Martin-Loeches, Ignacio, Maor, Yasmin, Strahilevitz, Jacob, Battaglia, Salvatore, Carrabba, Maria, Ceriana, Piero, Confalonieri, Marco, Monforte, Antonella d’Arminio, Prato, Bruno Del, Rosa, Marino De, Fantini, Riccardo, Faverio, Paola, Fiorentino, Giuseppe, Gammino, Maria Antonia, Menzella, Francesco, Milani, Giuseppe, Nava, Stefano, Palmiero, Gerardo, Petrino, Roberta, Gabrielli, Barbara, Rossi, Paolo, Sorino, Claudio, Steinhilber, Gundi, Zanforlin, Alessandro, Franzetti, Fabio, Carugati, Manuela, Morosi, Manuela, Monge, Elisa, Carone, Mauro, Patella, Vincenzo, Scarlata, Simone, Comel, Andrea, Kurahashi, Kiyoyasu, Bacha, Zeina Aoun, Ugalde, Daniel Barajas, Zuñiga, Omar Ceballos, Villegas, José F., Medenica, Milic, Garde, E.M.W. van de, Mihsra, Deebya Raj, Shrestha, Poojan, Ridgeon, Elliott, Awokola, Babatunde Ishola, Nwankwo, Ogonna N.O., Olufunlola, Adefuye Bolanle, Olumide, Segaolu, Ukwaja, Kingsley N., Irfan, Muhammad, Minarowski, Lukasz, Szymon, Skoczyński, Froes, Felipe, Leuschner, Pedro, Meireles, Mariana, Ferrão, Cláudia, Neves, João, Ravara, Sofia B., Brocovschii, Victoria, Ion, Chesov, Rusu, Doina, Toma, Cristina, Chirita, Daniela, Dorobat, Carmen Mihaela, Birkun, Alexei, Kaluzhenina, Anna, Almotairi, Abdullah, Ali Bukhary, Zakeya Abdulbaqi, Edathodu, Jameela, Fathy, Amal, Abdulaziz Enani, Abdullah Mushira, Mohamed, Nazik Eltayeb, Memon, Jawed Ulhadi, Bella, Abdelhaleem, Bogdanović, Nada, Milenkovic, Branislava, Pesut, Dragica, Borderìas, Luis, Bordon Garcia, Noel Manuel, Alarcón, Hugo Cabello, Cilloniz, Catia, Torres, Antoni, Diaz-Brito, Vicens, Casas, Xavier, González, Alicia Encabo, Fernández-Almira, Maria Luisa, Gallego, Miguel, Gaspar-García, Inmaculada, Castillo, Juan González del, Victoria, Patricia Javaloyes, Martínez, Elena Laserna, Molina, Rosa Malo de, Marcos, Pedro J., Menéndez, Rosario, Pando-Sandoval, Ana, Aymerich, Cristina Prat, Torre, Alicia Lacoma de la, García-Olivé, Ignasi, Rello, Jordi, Moyano, Silvia, Sanz, Francisco, Sibila, Oriol, Rodrigo-Troyano, Ana, Solé-Violán, Jordi, Uranga, Ane, Boven, Job F.M. van, Torra, Ester Vendrell, Pujol, Jordi Almirall, Feldman, Charles, Yum, Ho Kee, Fiogbe, Arnauld Attannon, Yangui, Ferdaous, Bilaceroglu, Semra, Dalar, Levent, Yilmaz, Ufuk, Bogomolov, Artemii, Elahi, Naheed, Dhasmana, Devesh J., Feneley, Andrew, Ions, Rhiannon, Skeemer, Julie, Woltmann, Gerrit, Hancock, Carole, Hill, Adam T., Rudran, Banu, Ruiz-Buitrago, Silvia, Campbell, Marion, Whitaker, Paul, Youzguin, Alexander, Singanayagam, Anika, Allen, Karen S., Brito, Veronica, Dietz, Jessica, Dysart, Claire E., Kellie, Susan M., Franco-Sadud, Ricardo A., Meier, Garnet, Holland, Thomas L., Bergin, Stephen P., Kheir, Fayez, Landmeier, Mark, Lois, Manuel, Nair, Girish B., Patel, Hemali, Reyes, Katherine, Rodriguez-Cintron, William, Saito, Shigeki, Soni, Nilam J., Noda, Julio, Hinojosa, Cecilia I., Levine, Stephanie M., Angel, Luis F., Reyes, Luis F., Anzueto, Antonio, Whitlow, K. Scott, Hipskind, John, Sukhija, Kunal, Totten, Vicken, Wunderink, Richard G., Shah, Ray D., Mateyo, Kondwelani John, Noriega, Lorena, Alvarado, Ezequiel, Aman, Mohamed, Labra, Lucía, Pascual-Guardia, Sergi, Amati, Francesco, Marin-Corral, Judith, Aliberti, Stefano, Gea, Joaquim, Rodriguez, Alejandro, Sotgiu, Giovanni, Meyer, Christian N., Anzueto, Antonio R., and Restrepo, Marcos I.

Published
2023
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35. Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline

Author

Nahid, Payam, Mase, Sundari R, Migliori, Giovanni Battista, Sotgiu, Giovanni, Bothamley, Graham H, Brozek, Jan L, Cattamanchi, Adithya, Cegielski, J Peter, Chen, Lisa, Daley, Charles L, Dalton, Tracy L, Duarte, Raquel, Fregonese, Federica, Horsburgh, C Robert, Khan, Faiz Ahmad, Kheir, Fayez, Lan, Zhiyi, Lardizabal, Alfred, Lauzardo, Michael, Mangan, Joan M, Marks, Suzanne M, McKenna, Lindsay, Menzies, Dick, Mitnick, Carole D, Nilsen, Diana M, Parvez, Farah, Peloquin, Charles A, Raftery, Ann, Schaaf, H Simon, Shah, Neha S, Starke, Jeffrey R, Wilson, John W, Wortham, Jonathan M, Chorba, Terence, and Seaworth, Barbara

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Biodefense, Antimicrobial Resistance, Lung, Vaccine Related, Emerging Infectious Diseases, Rare Diseases, Prevention, Tuberculosis, Infectious Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Antitubercular Agents, Drug Administration Schedule, Drug Therapy, Combination, Humans, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, MDR-TB, tuberculosis, duration of treatment, drug treatment, treatment monitoring, Medical and Health Sciences, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Background: The American Thoracic Society, U.S. Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Diseases Society of America jointly sponsored this new practice guideline on the treatment of drug-resistant tuberculosis (DR-TB). The document includes recommendations on the treatment of multidrug-resistant TB (MDR-TB) as well as isoniazid-resistant but rifampin-susceptible TB.Methods: Published systematic reviews, meta-analyses, and a new individual patient data meta-analysis from 12,030 patients, in 50 studies, across 25 countries with confirmed pulmonary rifampin-resistant TB were used for this guideline. Meta-analytic approaches included propensity score matching to reduce confounding. Each recommendation was discussed by an expert committee, screened for conflicts of interest, according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology.Results: Twenty-one Population, Intervention, Comparator, and Outcomes questions were addressed, generating 25 GRADE-based recommendations. Certainty in the evidence was judged to be very low, because the data came from observational studies with significant loss to follow-up and imbalance in background regimens between comparator groups. Good practices in the management of MDR-TB are described. On the basis of the evidence review, a clinical strategy tool for building a treatment regimen for MDR-TB is also provided.Conclusions: New recommendations are made for the choice and number of drugs in a regimen, the duration of intensive and continuation phases, and the role of injectable drugs for MDR-TB. On the basis of these recommendations, an effective all-oral regimen for MDR-TB can be assembled. Recommendations are also provided on the role of surgery in treatment of MDR-TB and for treatment of contacts exposed to MDR-TB and treatment of isoniazid-resistant TB.

Published
2019

37. Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools

Author

Saderi, Laura, Puci, Mariangela, Di Lorenzo, Biagio, Centis, Rosella, D’Ambrosio, Lia, Akkerman, Onno W., Alffenaar, Jan-Willem C., Caminero, José A., Chakaya, Jeremiah Muhwa, Denholm, Justin T., Kurhasani, Xhevat, Ong, Catherine W.M., Rendon, Adrian, Silva, Denise Rossato, Tiberi, Simon, Zenner, Dominik, Cabibbe, Andrea M., Migliori, Giovanni Battista, and Sotgiu, Giovanni

Published
2022
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38. A Prospective Cohort Analysis of the Prevalence and Predictive Factors of Delayed Discharge After Laparoscopic Cholecystectomy in Italy: The DeDiLaCo Study

Author

Cillara, Nicola, Podda, Mauro, Cicalò, Enrico, Sotgiu, Giovanni, Provenzano, Maria, Fransvea, Pietro, Poillucci, Gaetano, Sechi, Raffaele, Deserra, Antonello, DʼAgostino, Francesca, Margiani, Carla, Scabini, Stefano, Pertile, Davide, Rosa, Raffaele De, Prosperi, Paolo, Bruscino, Alessandro, Bella, Annamaria Di, Casati, Massimiliano, Laface, Letizia, Abate, Emmanuele, Frontali, Alice, Bonomi, Alessandro Michele, Ferrario, Luca, Mucilli, Felice, Barone, Mirko, Borghi, Felice, Sasia, Diego, Giraudo, Giorgio, Puzziello, Alessandro, Loffredo, Andrea, Steccanella, Francesca, Donnarumma, Elio, Galleano, Raffaele, Malerba, Michele, Runfola, Matteo, Agus, Marcello, Fortunato, Federica, Calò, Pietro Giorgio, Medas, Fabio, Canu, Gian Luigi, Stella, Marco, Ferrara, Francesco, Baldi, Caterina, Benuzzi, Laura, Pisanu, Adolfo, Saba, Alessandra, Gessa, Emanuela, Muratore, Andrea, Calabrò, Marcello, Cuzzola, Bruno, Garino, Mauro, Marafante, Chiara, Farfaglia, Roberto, Pandolfo, Gianpiero, Pata, Giacomo, Lantone, Giulio, Marino, Fabio, Perrone, Fabrizio, Scognamillo, Fabrizio, Delogu, Daniele, Tilocca, Pier Luigi, Frena, Antonio, Malpaga, Anna, Bertelli, Giacomo, Memeo, Riccardo, Ferraro, Valentina, Libia, Annarita, Sarro, Giuliano, Marconi, Matteo, Nava, Samuele, Pierpaolo, Bordoni, Fleres, Francesco, Clarizia, Guglielmo, Alfieri, Sergio, Rosa, Fausto, Longo, Fabio, Restini, Enrico, Cianci, Pasquale, Capuzzolo, Sabino, Anania, Gabriele, Bombardini, Cristina, Urbani, Alessia, Bona, Davide, Aiolfi, Alberto, Lastraioli, Caterina, Paola, Massimiliano Di, DallʼOglio, Anna, D’Eletto, Marco, Capelli, Patrizio, Conti, Luigi, Luzietti, Enrico, Banchini, Filippo, Manca, Giuseppe, Calo, Gabriele’, Centomze, Antonella, Andreano, Mauro, Sullo, Pasquale, Giuseppina, Oliva, Anastasi, Alessandro, Canonico, Giuseppe, Nelli, Tommaso, Trompetto, Mario, Gallo, Gaetano, Clerico, Giuseppe, Arganini, Marco, Palmeri, Matteo, Bonuso, Claudio, Mirabella, Antonello, Marino, Marco V., Vaccarella, Gianpaolo, Salzano, Francesco, Meccariello, Renato, Mastrorilli, Maurizio, Campanile, Fabio Cesare, Foti, Nicola, Angelis, Monica De, Palma, Giovanni Domenico De, Aprea, Giovanni, Palomba, Giuseppe, Milone, Marco, Capano, Mariana, Manigrasso, Michele, Baldazzi, Gianandrea, Cassini, Diletta, Epifani, Angelo Gabriele, Bottino, Vincenzo, Canfora, Alfonso, Ferronetti, Antonio, de Manzini, Nicolò, Biloslavo, Alan, Fracon, Stefano, Filauro, Marco, Barberis, Andrea, Azzinnaro, Antonio, Oliva, Alba, Razzore, Andrea, Maira, Lorenzo Di, Bima, Carlo, Gibin, Enrico, Peluso, Chiara, Perrotta, Nicola, Celiento, Marta, Scorzelli, Marco, Tuveri, Antonio, Madeddu, Francesco, Fois, Claudia, Russello, Domenico, Latteri, Saverio, Sofia, Maria, Rio, Paolo Del, Cozzani, Federico, Giuffrida, Mario, Mariani, Pierpaolo, Giussani, Martina, Ansaloni, Luca, Maestri, Marcello, Tartaglia, Giuseppe, Caricato, Marco, Capolupo, Gabriella Teresa, Carannante, Filippo, Gambino, Giovanni, Bertino, Vanessa, Bonilauri, Stefano, Frazzetta, Giuseppe, Amodio, Pietro Maria, Siena, Teresa De, Zanzi, Federico, Guariniello, Anna, Rocco, Giuseppe, Mancini, Stefano, Sagnotta, Andrea, Solinas, Luigi, Porta, Andrea, Sambucci, Daniele, Monti, Eleonora, Quaglino, Francesco, Mantova, Serena, Fiore, Alessia, Costi, Renato, Virgilio, Edoardo, Montali, Filippo, Catarci, Marco, Apa, Daniela, Bertoldi, Innocenzo, Camandona, Michele, Bossotti, Maurizio, Palagi, Silvia, Doria, Emaunele, Caltagirone, Alice, Balani, Alessandro, Petronio, Barbara, Terranova, Susanna, Martuzzi, Federica, Romeo, Carlo, Carluccio, Raffaele, Neri, Silvia, Auriemma, Pasquale Pio, Prestigiacomo, Giorgia, Sala, Stefano, Colli, Francesco, Marini, Pierluigi, Cosimo, Carla Di, Gattolin, Andrea, Rimonda, Roberto, Travaglio, Elisabetta, Cotsoglou, Christian, Granieri, Stefano, Chierici, Andrea Piero, Tamini, Nicolò, Pitoni, Ludovica, Vico, Eleonora, Altomare, Donato Francesco, Martines, Gennaro, Tomasicchio, Giovanni, Coppola, Massimiliano, Aprile, Giovanna, Sau, Paolo, Papa, Mauro Del, Manzi, Fulvio, DʼAmata, Gabriele, Cocorullo, Gianfranco, Venturelli, Paolina, Carollo, Giuseppe, Tondolo, Vincenzo, Dore, Andrea, Giorgio, Danilo Di, Gusai, Giovanni Pietro Paolo, Salaris, Claudia, Sanna, Silvia, Pignata, Giusto, Andreuccetti, Jacopo, DʼAlessio, Rossella, Massani, Marco, Tutino, Roberta, Viola, Vincenzo, Stella, Luigi Persico, Diana, Massimo, Sampietro, Gianluca Matteo, Merlini, David Alessio, Sica, Giuseppe, Bagaglini, Giulia, Manzia, Tommaso Maria, Siracusa, Leandro, Tisone, Giuseppe, Ercolani, Giorgio, DʼAcapito, Fabrizio, Pietrantonio, Daniela Di, Fiscon, Valentino, Portale, Giuseppe, Cipollari, Chiara, Sorrentino, Mario, Piccolo, Roberta, Cojutti, Alessandro, Canova, Gualtiero, Nicotera, Antonella, Zago, Marcello, Montis, Giorgio De, Castaldi, Fabio, Morelli, Maria Morena, Parma, Emilio, Paolini, Claudia, Marco, Giovanni De, Elter, Chiara, Feo, Carlo V., Fabbri, Nicolò, Severi, Silvia, Nasto, Aurelio, Patrone, Renato, Conti, Lorenzo, Rizzi, Andrea, Broggi, Luca, Danelli, Piergiorgio, Cammarata, Francesco, Fiore, Luigi, Grande, Michele, Campanelli, Michela, and Grande, Simona

Published
2023
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40. Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis

Author

Nasiri, Mohammad Javad, Zangiabadian, Moein, Arabpour, Erfan, Amini, Sirus, Khalili, Farima, Centis, Rosella, D'Ambrosio, Lia, Denholm, Justin T., Schaaf, H. Simon, van den Boom, Martin, Kurhasani, Xhevat, Dalcolmo, Margareth Pretti, Al-Abri, Seif, Chakaya, Jeremiah, Alffenaar, Jan-Willem, Akkerman, Onno, Silva, Denise Rossato, Muňoz-Torrico, Marcela, Seaworth, Barbara, Pontali, Emanuele, Saderi, Laura, Tiberi, Simon, Zumla, Alimuddin, Migliori, Giovanni Battista, and Sotgiu, Giovanni

Published
2022
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42. Infant BCG vaccination and risk of pulmonary and extrapulmonary tuberculosis throughout the life course: a systematic review and individual participant data meta-analysis

Author

Martinez, Leonardo, Cords, Olivia, Liu, Qiao, Acuna-Villaorduna, Carlos, Bonnet, Maryline, Fox, Greg J, Carvalho, Anna Cristina C, Chan, Pei-Chun, Croda, Julio, Hill, Philip C, Lopez-Varela, Elisa, Donkor, Simon, Fielding, Katherine, Graham, Stephen M, Espinal, Marcos A, Kampmann, Beate, Reingold, Arthur, Huerga, Helena, Villalba, Julian A, Grandjean, Louis, Sotgiu, Giovanni, Egere, Uzochukwu, Singh, Sarman, Zhu, Limei, Lienhardt, Christian, Denholm, Justin T, Seddon, James A, Whalen, Christopher C, García-Basteiro, Alberto L, Triasih, Rina, Chen, Cheng, Singh, Jitendra, Huang, Li-Min, Sharma, Surendra, Hannoun, Djohar, del Corral, Helena, Mandalakas, Anna M, Malone, LaShaunda L, Ling, Du-Lin, Kritski, Afrânio, Stein, Catherine M, Vashishtha, Richa, Boulahbal, Fadila, Fang, Chi-Tai, Boom, W Henry, Netto, Eduardo Martins, Lemos, Antonio Carlos, Hesseling, Anneke C, Kay, Alexander, Jones-López, Edward C, Horsburgh, C Robert, Lange, Christoph, and Andrews, Jason R

Published
2022
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44. Pharmacodynamic analysis of a fluid challenge with 4 ml kg−1 over 10 or 20 min: a multicenter cross-over randomized clinical trial

Author

Messina, Antonio, Palandri, Chiara, De Rosa, Silvia, Danzi, Vinicio, Bonaldi, Efrem, Montagnini, Claudia, Baino, Sara, Villa, Federico, Sala, Francesca, Zito, Paola, Negri, Katerina, Della Corte, Francesco, Cammarota, Gianmaria, Saderi, Laura, Sotgiu, Giovanni, Monge García, Manuel Ignacio, and Cecconi, Maurizio

Published
2022
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45. Proposal of a New Composite Score (DAMADECO) to Simultaneously Evaluate Asthma and CRSwNP Severity in Comorbid Patients.

Author

D'Amato, Maria, Pasqualetti, Patrizio, Cantone, Elena, Caminati, Marco, Bonini, Matteo, Di Marco, Fabiano, Pipolo, Carlotta, Seccia, Veronica, Sotgiu, Giovanni, and De Corso, Eugenio

Subjects
COMORBIDITY, NASAL polyps, RESPIRATORY diseases, RESEARCH personnel, ASTHMA
Abstract

Background: Asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) are chronic respiratory conditions that frequently coexist. However, an integrated assessment tool for both conditions is currently lacking. This study aimed to develop and preliminarily evaluate a composite score capable of simultaneously assessing asthma and CRSwNP in comorbid patients. Methods: An expert panel comprising three pulmonologists, one allergist/clinical immunologist, and four ear, nose and throat (ENT) specialists developed a tool to capture asthma and CRSwNP severity. The tool (D'Amato-De Corso score, or DAMADECO score) incorporates eight parameters, four specific to asthma and four specific to CRSwNP, to assign individual scores for each condition. A composite score is then calculated to reflect the overall disease burden (ranging from −8: poor control and +8: optimal control). A retrospective pilot study was conducted to evaluate the tool. Results: The DAMADECO composite score was applied to 21 comorbid patients. The mean partial scores for asthma and CRSwNP were −1.57 and −1.67, respectively, with a mean total composite score of −3.24. A total of 13 out of 21 patients had uncontrolled domains in both diseases, while fewer patients had only uncontrolled domains in asthma (1/21) or CRSwNP (6/21). The DAMADECO score also allows researchers to track disease progression and monitor treatment effectiveness. Conclusions: The preliminary results suggest that the DAMADECO score is a promising tool for simultaneously assessing asthma and CRSwNP, addressing the unmet need for an integrated approach to comorbid respiratory diseases. Further validation studies are needed to validate the tool in larger patient populations. [ABSTRACT FROM AUTHOR]

Published
2025
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46. The effect of benralizumab on inflammation in severe asthma: a real-life analysis.

Author

Visca, Dina, Ardesi, Francesco, Zappa, Martina, Grossi, Sarah, Pignatti, Patrizia, Vanetti, Marco, Pini, Laura, Sotgiu, Giovanni, Centis, Rosella, Migliori, Giovanni Battista, and Spanevello, Antonio

Subjects
ASTHMATICS, BIOTHERAPY, PNEUMONIA, QUALITY of life, DISEASE remission
Abstract

Background: Benralizumab is a monoclonal antibody treatment for severe eosinophilic asthma (SEA). Few studies investigated its role in airway inflammation and its correlation with lung function. Objectives: The aim of the present study is to assess its effect after 1 year of treatment, focusing on airway inflammation. Design: This is a retrospective observational study, in an Italian tertiary reference centre specialised in diagnosis and management of severe asthma patients. Methods: We conducted a monocentric retrospective study including SEA patients treated with benralizumab for 1 year. Clinical, functional and inflammatory data were collected at baseline, 6 (T6) and 12 (T12) months. Results: Twenty-two SEA patients on benralizumab were included. We observed a reduction in exacerbations rate and systemic steroid treatment (p < 0.0001) as well as an improvement in asthma control (p < 0.0001), health-related quality of life (p = 0.017) and lung function pre-BD FEV1 (L) (p = 0.02) and percentage (p = 0.004) and post-BD FEV1 (L) (p = 0.01) and percentage (p = 0.003) from baseline to T6 and T12. A reduction in sputum eosinophil percentage was observed at T6 and T12 (p < 0.005). We found a positive correlation between the variation of sputum eosinophils percentage and FEV1 (L) at T12 (rho = −0.79, p = 0.04). Moreover, the improvement of FEF25%–75% from baseline to 6 (rho = −0.53, p = 0.03) and 12 (rho = −0.62, p = 0.01) months negatively correlated with the duration of asthma disease. In our cohort 12/22 patients were super-responders at T6 and 15/22 at T12. Furthermore, clinical remission was reached by 12/22, and all of them obtained blood and sputum eosinophils counts normalisation. Conclusion: Our data confirm that it is a rapid and effective treatment for SEA acting on clinical, functional, systemic and airway inflammatory outcomes. Our results highlight the role of induced sputum as a promising non-invasive technique to investigate pathophysiologic mechanisms in severe asthma treated with biologics. Finally, a negative correlation between small airway improvement and the duration of asthma may suggest that a prompt referral to asthma centres may delay lung function worsening. Additional studies are needed to investigate more in-depth the role of induced sputum in the management of asthma, response to treatment and remission. Plain language summary: Analysis of the effect of a biological therapy on severe asthma Background: Asthma is estimated to affect almost 5%-8% of the European adult population, and 5%–10% of these patients suffer from a severe asthma form. Severe asthma is characterised by chronic airway inflammation despite traditional inhaled treatment and patients may experience acute flare ups requiring courses of steroids and eventually hospitalization leading to a poor quality of life. New biological drugs have been introduced to treat severe asthma characterized by inflammation in the blood and in the lungs. Benralizumab is a well known biological option for severe asthmatic patients. Methods: We provide data on 22 patients followed up in our tertiary severe asthma centre in Tradate, Italy, affected by severe eosinophilic asthma treated with benralizumab for at least one year. Results: Our data confirmed a rapid effect of benralizumab on respiratory symptoms, exacerbations and quality of life. In addition, we documented a significant improvement in lung function along with a normalization of inflammation in the blood and in the lungs, assessed with a non-invasive tool: the induced sputum. Conclusions: Interestingly, our data highlight the importance of induced sputum as a promising non-invasive technique to investigate pathophysiologic mechanisms in severe asthma treated with biologics. Additional studies are needed to implement its role in the management of asthma also in terms of response to treatment towards a personalized approach. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis

Author

treatment–2017, The Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB, Ahmad, Nafees, Ahuja, Shama D, Akkerman, Onno W, Alffenaar, Jan-Willem C, Anderson, Laura F, Baghaei, Parvaneh, Bang, Didi, Barry, Pennan M, Bastos, Mayara L, Behera, Digamber, Benedetti, Andrea, Bisson, Gregory P, Boeree, Martin J, Bonnet, Maryline, Brode, Sarah K, Brust, James CM, Cai, Ying, Caumes, Eric, Cegielski, J Peter, Centis, Rosella, Chan, Pei-Chun, Chan, Edward D, Chang, Kwok-Chiu, Charles, Macarthur, Cirule, Andra, Dalcolmo, Margareth Pretti, D'Ambrosio, Lia, de Vries, Gerard, Dheda, Keertan, Esmail, Aliasgar, Flood, Jennifer, Fox, Gregory J, Fréchet-Jachym, Mathilde, Fregona, Geisa, Gayoso, Regina, Gegia, Medea, Gler, Maria Tarcela, Gu, Sue, Guglielmetti, Lorenzo, Holtz, Timothy H, Hughes, Jennifer, Isaakidis, Petros, Jarlsberg, Leah, Kempker, Russell R, Keshavjee, Salmaan, Khan, Faiz Ahmad, Kipiani, Maia, Koenig, Serena P, Koh, Won-Jung, Kritski, Afranio, Kuksa, Liga, Kvasnovsky, Charlotte L, Kwak, Nakwon, Lan, Zhiyi, Lange, Christoph, Laniado-Laborín, Rafael, Lee, Myungsun, Leimane, Vaira, Leung, Chi-Chiu, Leung, Eric Chung-Ching, Li, Pei Zhi, Lowenthal, Phil, Maciel, Ethel L, Marks, Suzanne M, Mase, Sundari, Mbuagbaw, Lawrence, Migliori, Giovanni B, Milanov, Vladimir, Miller, Ann C, Mitnick, Carole D, Modongo, Chawangwa, Mohr, Erika, Monedero, Ignacio, Nahid, Payam, Ndjeka, Norbert, O'Donnell, Max R, Padayatchi, Nesri, Palmero, Domingo, Pape, Jean William, Podewils, Laura J, Reynolds, Ian, Riekstina, Vija, Robert, Jérôme, Rodriguez, Maria, Seaworth, Barbara, Seung, Kwonjune J, Schnippel, Kathryn, Shim, Tae Sun, Singla, Rupak, Smith, Sarah E, Sotgiu, Giovanni, Sukhbaatar, Ganzaya, Tabarsi, Payam, Tiberi, Simon, Trajman, Anete, Trieu, Lisa, Udwadia, Zarir F, van der Werf, Tjip S, and Veziris, Nicolas

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Clinical Research, Tuberculosis, Lung, Antimicrobial Resistance, Prevention, Clinical Trials and Supportive Activities, Rare Diseases, Orphan Drug, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Infection, Good Health and Well Being, Amikacin, Antitubercular Agents, Capreomycin, Carbapenems, Clofazimine, Diarylquinolines, Drug Therapy, Combination, Fluoroquinolones, Humans, Kanamycin, Levofloxacin, Linezolid, Moxifloxacin, Recurrence, Treatment Failure, Tuberculosis, Multidrug-Resistant, Tuberculosis, Pulmonary, Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB treatment–2017, Medical and Health Sciences, General & Internal Medicine, Biomedical and clinical sciences, Health sciences
Abstract

BackgroundTreatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis.MethodsIn this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration.FindingsOf 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses.InterpretationAlthough inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition.FundingAmerican Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Published
2018

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