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肺结核治疗中断的特征、预测因素及后果:一项多中心回顾性队列研究。

Characteristics, predictors and consequences of tuberculosis treatment interruption: A multicentre retrospective cohort study.

机构信息

Centre of Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

Department of Pharmacy, Sarawak General Hospital, Ministry of Health Malaysia, Kuching, Sarawak, Malaysia.

出版信息

Trop Med Int Health. 2024 May;29(5):434-445. doi: 10.1111/tmi.13987. Epub 2024 Mar 12.

Abstract

OBJECTIVES

Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption.

METHODS

We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant.

RESULTS

Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%).

CONCLUSION

Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

摘要

目的

治疗中断与结核病(TB)治疗结局不佳和耐药性增加有关。为了解决这一问题,我们旨在研究治疗中断的特征、预测因素和后果。

方法

我们通过检索马来西亚砂拉越 10 家公共卫生诊所 4 年(2018-2021 年)的结核病患者记录,进行了一项回顾性队列研究。选择患有药物敏感型结核病的成年患者(≥18 岁)。治疗中断定义为治疗期间累计中断≥2 周。采用卡方检验、Mann-Whitney U 检验、Kaplan-Meier 检验和 Cox 比例风险回归分析数据,p<0.05 为统计学显著。

结果

在 2953 名符合条件的患者中,475 名(16.1%)发生了结核病治疗中断。中断最常发生在强化期(46.9%,n=223),治疗开始后前 4 周风险最大。强化期的中位中断时间为 2 周,强化期末累积中断概率为 12.9%。值得注意的是,144 名患者(30.3%)在强化期和继续期都发生了治疗中断,而其余 108 名患者(22.7%)仅在继续期发生了中断,中位中断时间为 16 周。有三个预测因素被确定为增加治疗中断的风险:药物不良反应(aHR=8.53,95%Cl:6.73-10.82)、吸烟(aHR=2.67,95%Cl:2.03-3.53)和非法药物使用(aHR=1.88,95%Cl:1.03-3.45)。相反,患有基础糖尿病与治疗中断的可能性降低相关(aHR=0.72,95%Cl:0.58-0.90)。治疗中断导致治疗重新开始(62.3%对 0.7%)、药物改变(47.8%对 4.9%)、治疗持续时间延长(247 天 [IQR=105]对 194 天 [IQR=44.3])和成功率降低(86.5%对 99.9%)有显著差异。

结论

了解治疗中断的时间特征、预测因素和负面后果,可以指导制定与时间相关的方法来减轻这一问题。

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