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基于贝叶斯Cox回归模型的耐多药结核病患者死亡影响因素

Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model.

作者信息

Wang Zhiyong, Zhang Yuqi, Gao Wenlong, Li Zongyu, Li Ming, Luo Qiuxia, Xiang Yuanyuan, Bao Kai

机构信息

Lanzhou Pulmonary Hospital, Lanzhou 730030.

Department of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou 730000, China.

出版信息

Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Nov 28;48(11):1659-1668. doi: 10.11817/j.issn.1672-7347.2023.230226.

Abstract

OBJECTIVES

Multidrug-resistant tuberculosis (MDR-TB) has a high mortality and is always one of the major challenges in global TB prevention and control. Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients. For follow-up data, the Cox proportional hazards regression model is an important multifactor analysis method. However, the method has significant limitations in its application, such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model. Therefore, Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy, and compare the differences between these 2 methods in their application.

METHODS

Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1, 2017 to March 31, 2021. Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors. Conventional and Bayesian Cox regression models were established to estimate the hazard ratios () and their 95% confidence interval (95% ) for the factors affecting the death of MDR-TB patients. The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% of each variable. The smaller parameter standard deviation and narrower 95% range indicated the more reliable parameter estimation.

RESULTS

The median survival time (1st quartile, 3rd quartile) of the 388 MDR-TB patients included in the study was 10.18 (4.26, 18.13) months, with the longest survival time of 31.90 months. Among these patients, a total of 12 individuals died of MDR-TB and the mortality was 3.1%. The median survival time (1st quartile, 3rd quartile) for the deceased patients was 4.78(2.63, 6.93) months. The majority of deceased patients, accounting for 50%, experienced death within the first 5 months of anti-TB therapy, with the last mortality case occurring within the 13th month of therapy. The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications (=6.96, 95% 2.00 to 24.24, =0.002) and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up (=0.19, 95% 0.05 to 0.77, =0.020). In the results of Bayesian Cox regression model, the iterative history plot and Blue/Green/Red (BGR) plot for each parameter showed the good model convergence, and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture (=0.33, 95% 0.08 to 0.87). Additionally, compared to patients without complications, those with comorbidities had an approximately 6.80-fold increase in the risk of death (=7.80, 95% 1.90 to 21.91). Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up (=0.10, 95% 0.01 to 0.30). The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model, except for parameter standard deviations of receiving regular follow-up (Bayesian model was 0.77; conventional model was 0.72) and pulmonary cavities (Bayesian model was 0.73; conventional model was 0.73).

CONCLUSIONS

The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients. Complications are the main risk factors of death in MDR-TB patients, while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death. For data with a small sample size and low incidence of outcome, the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

摘要

目的

耐多药结核病(MDR-TB)死亡率高,一直是全球结核病防控的主要挑战之一。分析可能影响MDR-TB患者不良结局的因素,有助于改善对MDR-TB患者的系统管理并优化治疗策略。对于随访数据,Cox比例风险回归模型是一种重要的多因素分析方法。然而,该方法在应用中存在显著局限性,例如难以处理小样本量及其他实际问题对模型的影响。因此,本研究同时使用贝叶斯Cox回归模型和传统Cox回归模型分析MDR-TB患者抗结核治疗期间死亡的影响因素,并比较这两种方法在应用中的差异。

方法

数据来源于2017年11月1日至2021年3月31日在兰州肺科医院接受治疗的388例MDR-TB患者。采用生存分析方法分析MDR-TB患者治疗期间的死亡情况及其影响因素。建立传统Cox回归模型和贝叶斯Cox回归模型,以估计影响MDR-TB患者死亡的因素的风险比(HR)及其95%置信区间(95%CI)。通过比较各变量的参数标准差和95%CI评估这两种模型中参数估计的可靠性。参数标准差越小且95%CI范围越窄,表明参数估计越可靠。

结果

本研究纳入的388例MDR-TB患者的中位生存时间(第1四分位数,第3四分位数)为10.18(4.26,18.13)个月,最长生存时间为31.90个月。这些患者中,共有12例死于MDR-TB,死亡率为3.1%。死亡患者的中位生存时间(第1四分位数,第3四分位数)为4.78(2.63,6.93)个月。大多数死亡患者(占50%)在抗结核治疗的前5个月内死亡,最后一例死亡发生在治疗的第13个月。传统Cox回归模型结果显示,合并症的MDR-TB患者死亡风险比无并发症患者高约6.96倍(HR = 6.96,95%CI 2.00至24.24,P = 0.002),接受定期随访的患者死亡风险比未接受定期随访的患者降低约81%(HR = 0.19,95%CI 0.05至0.77,P = 0.020)。在贝叶斯Cox回归模型结果中,各参数的迭代历史图和蓝/绿/红(BGR)图显示模型收敛良好,参数估计表明首次痰培养阳性患者的死亡风险低于首次痰培养阴性患者(HR = 0.33,95%CI 0.08至0.87)。此外,与无并发症患者相比,合并症患者的死亡风险增加约6.80倍(HR = 7.80,95%CI 1.90至21.91)。接受定期随访的患者与未接受定期随访的患者相比,死亡风险降低90%(HR = 0.10,95%CI 0.01至0.30)。这两种模型的比较表明,除接受定期随访的参数标准差(贝叶斯模型为0.77;传统模型为0.72)和肺空洞的参数标准差(贝叶斯模型为0.73;传统模型为0.73)外,贝叶斯Cox模型中其他变量的参数标准差和相应的95%CI范围明显小于传统模型。

结论

抗结核治疗的第一年是MDR-TB患者死亡的高危期。并发症是MDR-TB患者死亡的主要危险因素,而接受定期随访且首次痰培养阳性的患者死亡风险较低。对于小样本量和结局发生率低的数据,贝叶斯Cox回归模型比传统Cox模型提供更可靠的参数估计。

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