临床诊断为急性鼻窦炎的成人的预后和抗生素获益预测:个体参与者数据荟萃分析

Jeroen Hoogland, Toshihiko Takada, Maarten van Smeden, Maroeska M Rovers, An I de Sutter, Daniel Merenstein, Laurent Kaiser, Helena Liira, Paul Little, Heiner C Bucher, Karel G M Moons, Johannes B Reitsma, Roderick P Venekamp
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摘要

背景:先前对临床诊断为急性鼻窦炎(ARS)的成人抗生素的个体参与者数据荟萃分析(IPD-MA)显示抗生素的总体边际效应,但在应用常规(即单变量或单变量一次)亚组分析时,无法确定最有可能从抗生素中获益的患者。我们更新了系统综述,并研究了患者水平预后和抗生素治疗效果的多变量预测是否可能导致对ARS患者进行更有针对性的治疗分配。方法:对9例抗生素治疗双盲安慰剂对照试验(n=2539)进行IPD-MA分析,以8-15天治愈概率为主要观察指标。建立了一个逻辑混合效应模型,根据人口统计学特征、体征和症状以及抗生素治疗分配来预测治愈的概率。根据内部和外部的交叉验证,从校准和鉴别性能、整体模型拟合和个体预测的准确性等方面对预测性能进行量化。结果:预后与治愈风险不能可靠预测(c统计量为0.58,Brier评分为0.24)。同样,患者水平的治疗效果预测也不能可靠地区分那些从抗生素中受益和没有受益的患者(c-for-benefit 0.50)。结论:总之,基于患者人口统计学和常见体征和症状的多变量预测不能可靠地预测IPD-MA患者水平的治愈概率和抗生素效果。因此,不能指望这些特征能够可靠地区分那些接受初级保健治疗的ARS患者是否受益于抗生素。
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Prognosis and prediction of antibiotic benefit in adults with clinically diagnosed acute rhinosinusitis: an individual participant data meta-analysis.

Background: A previous individual participant data meta-analysis (IPD-MA) of antibiotics for adults with clinically diagnosed acute rhinosinusitis (ARS) showed a marginal overall effect of antibiotics, but was unable to identify patients that are most likely to benefit from antibiotics when applying conventional (i.e. univariable or one-variable-at-a-time) subgroup analysis. We updated the systematic review and investigated whether multivariable prediction of patient-level prognosis and antibiotic treatment effect may lead to more tailored treatment assignment in adults presenting to primary care with ARS.

Methods: An IPD-MA of nine double-blind placebo-controlled trials of antibiotic treatment (n=2539) was conducted, with the probability of being cured at 8-15 days as the primary outcome. A logistic mixed effects model was developed to predict the probability of being cured based on demographic characteristics, signs and symptoms, and antibiotic treatment assignment. Predictive performance was quantified based on internal-external cross-validation in terms of calibration and discrimination performance, overall model fit, and the accuracy of individual predictions.

Results: Results indicate that the prognosis with respect to risk of cure could not be reliably predicted (c-statistic 0.58 and Brier score 0.24). Similarly, patient-level treatment effect predictions did not reliably distinguish between those that did and did not benefit from antibiotics (c-for-benefit 0.50).

Conclusions: In conclusion, multivariable prediction based on patient demographics and common signs and symptoms did not reliably predict the patient-level probability of cure and antibiotic effect in this IPD-MA. Therefore, these characteristics cannot be expected to reliably distinguish those that do and do not benefit from antibiotics in adults presenting to primary care with ARS.

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