Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis
Effect of Xpert MTB/RIF on clinical outcomes in routine care settings: individual patient data meta-analysis
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DOI：
10.1016/s2214-109x(18)30458-3
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发表时间：
2019-02-01
影响因子：
34.3
通讯作者：
Bandason, Tsitsi
中科院分区：
文献类型：
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作者：
Di Tanna, Gian Luca;Khaki, Ali Raza;Bandason, Tsitsi
背景 Xpert MTB/RIF 是使用最广泛的结核病自动核酸扩增检测，已在 130 多个国家/地区使用。尽管诊断准确性有据可查，但患者治疗效果的预期改善尚未明确。我们进行了个体患者数据荟萃分析，以检查与 Xpert MTB/RIF 相关的患者结果的改善。方法我们检索了 PubMed、Embase、ClinicalTrials.gov 和泛非临床试验注册中心（从开始到 2018 年 2 月 1 日），以查找比较使用 Xpert MTB/RIF 与痰涂片镜检作为成人（18 岁或以上）结核病诊断测试的随机对照试验 (RCT)。我们排除了肺外结核患者的研究以及未评估死亡率的研究。我们使用两阶段方法进行初步分析，并使用一阶段方法进行敏感性分析。为了评估累积 6 个月全因死亡率的主要结果，我们首先对每项试验进行逻辑回归模型（整群随机试验的随机效应，多中心研究的稳健 SE），然后通过固定效应（逆方差）或随机效应（Der Simonian Laird）荟萃分析汇总优势比（OR）估计值。我们根据年龄和性别进行了调整，并根据艾滋病毒状况和既往结核病治疗史进行了分层。该研究方案已在 PROSPERO 注册，编号 CRD42014013394。 结果 我们的搜索确定了 387 项研究，其中 5 项 RCT 符合分析条件。在五个低收入和中等收入国家（南非、巴西、津巴布韦、赞比亚和坦桑尼亚），使用 Xpert MTB/RIF（Xpert 组）与痰涂片镜检（痰涂片组）对 8567 名成人诊所参加者（7074 名有数据的参与者中的 4490 名 [63.5%] 为 HIV 阳性）进行了结核病检测。主要结局（在三项研究中报告）发生在 Xpert 组 4050 名患者中的 182 名 (4.5%) 和涂片组 4093 名患者中的 217 名 (5.3%)（合并调整 OR 0.88，95% CI 0.68-1.14 [p=0.34]；对于 HIV 阳性个体 OR 0.83，0.65-1.05 [p=0.12]）。 Kaplan-Meier 估计显示，HIV 阳性患者的死亡率较低（Xpert 组每 100 人年 12.73 人，而痰涂片组每 100 人年 16.38 人）（风险比 0.76，95% CI 0.60-0.97；p=0.03）。偏倚风险被评估为合理，并且研究之间的统计异质性较低（I-2
Background Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF.Methods We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394.Findings Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63.5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4.5%) of 4050 patients in the Xpert group and 217 (5.3%) of 4093 patients in the smear group (pooled adjusted OR 0.88, 95% CI 0.68-1.14 [p=0.34]; for HIV-positive individuals OR 0.83, 0.65-1.05 [p=0.12]). Kaplan-Meier estimates showed a lower rate of death (12.73 per 100 person-years in the Xpert group vs 16.38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0.76, 95% CI 0.60-0.97; p=0.03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I-2