Division of Infectious Diseases, Allergy, and Immunology, Department of Internal Medicine, Saint Louis University School of Medicine, 1100 South Grand Blvd #817, Doisy Research Center, St. Louis, MO, 63104, USA.
Pfizer Inc., Collegeville, PA, USA.
BMC Infect Dis. 2021 Oct 27;21(1):1106. doi: 10.1186/s12879-021-06812-2.
Influenza is associated with excess morbidity and mortality of individuals each year. Few therapies exist for treatment of influenza infection, and each require initiation as early as possible in the course of infection, making efficacy difficult to estimate in the hospitalized patient with lower respiratory tract infection. Using causal machine learning methods, we re-analyze data from a randomized trial of oseltamivir versus standard of care aimed at reducing clinical failure in hospitalized patients with lower respiratory tract infection during the influenza season.
This was a secondary analysis of the Rapid Empiric Treatment with Oseltamivir Study (RETOS). Conditional average treatment effects (CATE) and 95% confidence intervals were computed from causal forest including 85 clinical and demographic variables. RETOS was a multicenter, randomized, unblinded, trial of adult patients hospitalized with lower respiratory tract infections in Kentucky from 2009 through 2012. Adult hospitalized patients with lower respiratory tract infection were randomized to standard of care or standard of care plus oseltamivir as early as possible after hospital admission but within 24 h of enrollment. After randomization, oseltamivir was initiated in the treatment arm per package insert. The primary outcome was clinical failure, a composite measure including failure to reach clinical improvement within 7 days, transfer to intensive care 24 h after admission, or rehospitalization or death within 30 days.
A total of 691 hospitalized patients with lower respiratory tract infections were included in the study. The only subgroup of patients with a statistically significant CATE was those with laboratory-confirmed influenza infection with a 26% lower risk of clinical failure when treated with oseltamivir (95% CI 3.2-48.0%).
This study suggests that addition of oseltamivir to standard of care may decrease clinical failure in hospitalized patients with influenza-associated lower respiratory tract infection versus standard of care alone. These results are supportive of current recommendations to initiate antiviral treatment in hospitalized patients with confirmed or suspected influenza as soon as possible after admission. Trial registration Original trial: Clinical Trials.Gov; Rapid Empiric Treatment With Oseltamivir Study (RETOS) (RETOS); ClinicalTrials.gov Identifier: NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715.
每年流感都会导致大量个体发病和死亡。目前针对流感感染的治疗方法有限，而且每种方法都需要在感染早期尽快开始，因此对于患有下呼吸道感染的住院患者，评估疗效非常困难。我们使用因果机器学习方法，重新分析了一项针对奥司他韦与标准治疗比较的随机临床试验数据，该试验旨在降低流感季节住院患者下呼吸道感染的临床治疗失败率。
这是一项对奥司他韦快速经验性治疗研究（RETOS）的二次分析。因果森林中包含 85 项临床和人口统计学变量，计算条件平均治疗效果（CATE）和 95%置信区间。RETOS 是一项多中心、随机、非盲、临床试验，纳入了 2009 年至 2012 年期间肯塔基州因下呼吸道感染住院的成年患者。将下呼吸道感染住院的成年患者随机分为标准治疗组或标准治疗加奥司他韦组，在入院后尽早（但在入组后 24 小时内）开始治疗。随机分组后，按照说明书要求在治疗组中开始使用奥司他韦。主要结局是临床治疗失败，这是一个复合指标，包括 7 天内未达到临床改善、入院后 24 小时转入重症监护病房或 30 天内再次住院或死亡。
共有 691 例下呼吸道感染住院患者纳入研究。只有实验室确诊的流感感染患者亚组的 CATE 具有统计学意义，奥司他韦治疗组的临床治疗失败风险降低了 26%（95%CI 3.2-48.0%）。
本研究表明，与标准治疗相比，奥司他韦联合标准治疗可能降低流感相关下呼吸道感染住院患者的临床治疗失败率。这些结果支持目前的建议，即对确诊或疑似流感的住院患者，应在入院后尽快开始抗病毒治疗。
ClinicalTrials.gov；Rapid Empiric Treatment With Oseltamivir Study（RETOS）（RETOS）；ClinicalTrials.gov 标识符：NCT01248715 https://clinicaltrials.gov/ct2/show/NCT01248715。
