School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Penang, Malaysia; Faculty of Pharmacy, Universiti Teknologi MARA Puncak Alam Campus, 42300, Bandar Puncak Alam, Selangor, Malaysia.
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Gelugor, 11800, Penang, Malaysia.
Tuberculosis (Edinb). 2024 Sep;148:102553. doi: 10.1016/j.tube.2024.102553. Epub 2024 Jul 31.
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.
延迟痰菌阴转与药物敏感的涂阳肺结核患者治疗失败或复发的风险增加相关。在许多研究中已经确定了一些促成因素，但结果因地区和国家而异。因此，本研究旨在建立一个预测模型，解释马来西亚药物敏感的涂阳肺结核患者在开始抗结核药物治疗后两个月内痰菌阴转时间的影响因素。收集并分析了 2013 年至 2018 年期间在马来西亚北部地区一家三级医院随访的肺结核患者的回顾性数据。使用非线性混合效应建模软件（NONMEM 7.3.0）建立参数生存模型。最后，通过 Kaplan-Meier-可视化预测检查（KM-VPC）方法、基于核的危险率估计方法和抽样重要性重采样（SIR）方法进一步验证了模型。共纳入 224 例患者，其中强化期结束时仍有 34.4%（77/224）的患者痰菌阳性。戈珀特危险函数最能描述数据。与胸部 X 线严重程度的最小基线相比，中度和晚期病变的痰菌阴转危险分别降低了 39%和 33%（调整后的危险比（aHR）分别为 0.61；95%置信区间（95%CI）为 0.44-0.84 和 0.67，95%CI 为 0.53-0.84）。同时，与非药物滥用者相比，活动期和既往药物滥用者的危险分别降低了 59%（aHR，0.41；95%CI，0.23-0.73）和 48%（aHR，0.52；95%CI，0.35-0.79）。内部和外部验证最终模型的成功开发允许更好地估计痰菌阴转时间，并提供对其预测因子的关系的更好理解。
