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A CLINICAL PREDICTION MODEL FOR UNSUCCESSFUL PULMONARY TUBERCULOSIS TREATMENT OUTCOMES
Author
Peetluk, Lauren S.
Rebeiro, Peter F.
Ridolfi, Felipe M.
Andrade, Bruno de Bezerril
Santos, Marcelo Cordeiro
Kritski, Afranio
Durovni, Betina
Calvacante, Solange
Figueiredo, Marina C.
Haas, David W.
Liu, Dandan
Rolla, Valeria C.
Sterling, Timothy R.
Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil network
Rebeiro, Peter F.
Ridolfi, Felipe M.
Andrade, Bruno de Bezerril
Santos, Marcelo Cordeiro
Kritski, Afranio
Durovni, Betina
Calvacante, Solange
Figueiredo, Marina C.
Haas, David W.
Liu, Dandan
Rolla, Valeria C.
Sterling, Timothy R.
Regional Prospective Observational Research in Tuberculosis (RePORT)-Brazil network
Affilliation
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA. / Vanderbilt University School of Medicine. Department of Biostatistics. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine, Division of Infectious Diseases. Nashville, TN, USA / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Manaus, AM, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine, Division of Infectious Diseases. Nashville, TN, USA .
Vanderbilt University School of Medicine. Department of Medicine, Division of Infectious Diseases. Nashville, TN, USA / Meharry Medical College. Department of Internal Medicine. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA / Vanderbilt University School of Medicine. Department of Biostatistics. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA. / Vanderbilt University School of Medicine. Department of Biostatistics. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine, Division of Infectious Diseases. Nashville, TN, USA / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Universidade Salvador. Laureate Universities. Salvador, BA, Brasil / Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Salvador, BA, Brasil.
Fundação Medicina Tropical Dr. Heitor Vieira Dourado. Manaus, AM, Brasil / Universidade do Estado do Amazonas. Manaus, AM, Brasil.
Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine, Division of Infectious Diseases. Nashville, TN, USA .
Vanderbilt University School of Medicine. Department of Medicine, Division of Infectious Diseases. Nashville, TN, USA / Meharry Medical College. Department of Internal Medicine. Nashville, TN, USA.
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA / Vanderbilt University School of Medicine. Department of Biostatistics. Nashville, TN, USA.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
Vanderbilt University School of Medicine. Department of Medicine. Division of Epidemiology. Nashville, Tennessee, USA.
Abstract
Despite widespread availability of curative therapy, tuberculosis treatment outcomes remain suboptimal. Clinical prediction models can inform treatment strategies to improve outcomes. Using baseline clinical data, we developed a prediction model for unsuccessful TB treatment outcome and evaluated the incremental value of HIV-related severity and isoniazid acetylator status.
Methods: Data originated from the Regional Prospective Observational Research for Tuberculosis Brazil cohort, which enrolled newly-diagnosed tuberculosis patients in Brazil from 2015-2019. This analysis included participants with culture-confirmed, drug-susceptible pulmonary tuberculosis who started first-line anti-tuberculosis therapy and had ≥12 months of follow-up. The endpoint was unsuccessful tuberculosis treatment: composite of death, treatment failure, regimen switch, incomplete treatment, or not evaluated. Missing predictors were imputed. Predictors were chosen via bootstrapped backward selection. Discrimination and calibration were evaluated with c-statistics and calibration plots, respectively. Bootstrap internal validation estimated overfitting, and a shrinkage factor was applied to improve out-of-sample prediction. Incremental value was evaluated with likelihood ratio-based measures.
Results: Of 944 participants, 191 (20%) had unsuccessful treatment outcomes. The final model included seven baseline predictors: hemoglobin, HIV-infection, drug use, diabetes, age, education, and tobacco use. The model demonstrated good discrimination (c-statistic=0.77; 95% confidence interval: 0.73-0.80) and was well-calibrated (optimism-corrected intercept and slope: -0.12 and 0.89,
Downloaded from https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab598/6313211 by Fundacao Oswaldo Cruz (FIOCRUZ) user on 14 July 2021
respectively). HIV-related factors and isoniazid acetylation status did not improve prediction of the final model.
Conclusions: The prediction model, using information readily available at treatment initiation, performed well in this population. The findings may guide future work to allocate resources or inform targeted interventions for high-risk patients.
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