A time-to-event modelling of sputum conversion within two months after antituberculosis initiation among drug-susceptible smear positive pulmonary tuberculosis patients: Implementation of internal and external validation.

Publication date: Sep 01, 2024

Delayed sputum conversion has been associated with a higher risk of treatment failure or relapse among drug susceptible smear-positive pulmonary tuberculosis patients. Several contributing factors have been identified in many studies, but the results varied across regions and countries. Therefore, the current study aimed to develop a predictive model that explained the factors affecting time to sputum conversion within two months after initiating antituberculosis agents among Malaysian with drug-susceptible smear-positive pulmonary tuberculosis patients. Retrospective data of pulmonary tuberculosis patients followed up at a tertiary hospital in the Northern region of Malaysia from 2013 until 2018 were collected and analysed. Nonlinear mixed-effect modelling software (NONMEM 7. 3.0) was used to develop parametric survival models. The final model was further validated using Kaplan-Meier-visual predictive check (KM-VPC) approach, kernel-based hazard rate estimation method and sampling-importance resampling (SIR) method. A total of 224 patients were included in the study, with 34. 4 % (77/224) of the patients remained positive at the end of 2 months of the intensive phase. Gompertz hazard function best described the data. The hazard of sputum conversion decreased by 39 % and 33 % for moderate and advanced lesions as compared to minimal baseline of chest X-ray severity, respectively (adjusted hazard ratio (aHR), 0. 61; 95 % confidence intervals (95 % CI), (0. 44-0. 84) and 0. 67, 95 % CI (0. 53-0. 84)). Meanwhile, the hazard also decreased by 59 % (aHR, 0. 41; 95 % CI, (0. 23-0. 73)) and 48 % (aHR, 0. 52; 95 % CI, (0. 35-0. 79)) between active and former drug abusers as compared to non-drug abuser, respectively. The successful development of the internally and externally validated final model allows a better estimation of the time to sputum conversion and provides a better understanding of the relationship with its predictors.

Concepts Keywords
Hospital Adult
Malaysian Antitubercular Agents
Months Antitubercular Agents
Predictive Female
Tuberculosis Hazard
Humans
Malaysia
Male
Middle Aged
Mycobacterium tuberculosis
NONMEM
Pulmonary tuberculosis
Reproducibility of Results
Retrospective Studies
Sputum
Sputum conversion
Time Factors
Time to event
Treatment Outcome
Tuberculosis, Pulmonary
Young Adult

Semantics

Type Source Name
disease MESH pulmonary tuberculosis
disease MESH treatment failure
disease MESH relapse
drug DRUGBANK Tropicamide

Original Article

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