Janssen Pharmaceutical Research and Development, LLC, Titusville, NJ, United States of America.
Johnson & Johnson, New Brunswick, NJ, United States of America.
PLoS One. 2021 Aug 16;16(8):e0255887. doi: 10.1371/journal.pone.0255887. eCollection 2021.
Recent observational studies suggest increased aortic aneurysm or dissection (AAD) risk following fluoroquinolone (FQ) exposure but acknowledge potential for residual bias from unreported patient characteristics. The objective of our study is to evaluate the potential association between FQ, other common antibiotics and febrile illness with risk of AAD using a self-controlled case series (SCCS) study design.
Retrospective database analysis-SCCS.
Primary and Secondary Care.
51,898 patients across 3 US claims databases (IBM® MarketScan® commercial and Medicare databases, Optum Clinformatics).
FQ or other common antibiotics or febrile illness.
AAD.
We studied patients with exposures and AAD between 2012 and 2017 in 3 databases. Risk windows were defined as exposure period plus 30 days. Diagnostic analyses included p-value calibration to account for residual error using negative control exposures (NCE), and pre-exposure outcome analyses to evaluate exposure-outcome timing. The measure of association was the incidence rate ratio (IRR) comparing exposed and unexposed time.
Most NCEs produced effect estimates greater than the hypothetical null, indicating positive residual error; calibrated p (Cp) values were therefore used. The IRR following FQ exposure ranged from 1.13 (95% CI: 1.04-1.22 -Cp: 0.503) to 1.63 (95% CI: 1.45-1.84 -Cp: 0.329). An AAD event peak was identified 60 days before first FQ exposure, with IRR increasing between the 60- to 30- and 29- to 1-day pre-exposure periods. It is uncertain how much this pre-exposure AAD event peak reflects confounding versus increased antibiotic use after a surgical correction of AADs.
This study does not confirm prior studies. Using Cp values to account for residual error, the observed FQ-AAD association cannot be interpreted as significant. Additionally, an AAD event surge in the 60 days before FQ exposure is consistent with confounding by indication, or increased use of antibiotics post-surgery.
NCT03479736.
最近的观察性研究表明，氟喹诺酮（FQ）暴露后主动脉瘤或夹层（AAD）的风险增加，但承认未报告患者特征可能存在残留偏倚。我们研究的目的是使用自我对照病例系列（SCCS）研究设计评估 FQ、其他常见抗生素和发热疾病与 AAD 风险之间的潜在关联。
回顾性数据库分析-SCCS。
初级和二级保健。
3 个美国索赔数据库（IBM® MarketScan®商业和医疗保险数据库、Optum Clinformatics）中的 51898 名患者。
FQ 或其他常见抗生素或发热疾病。
AAD。
我们在 3 个数据库中研究了 2012 年至 2017 年期间有暴露和 AAD 的患者。风险窗口定义为暴露期加 30 天。诊断分析包括使用阴性对照暴露（NCE）进行剩余误差校准的 p 值（Cp）和评估暴露-结果时间的预暴露结果分析。关联的度量是比较暴露和未暴露时间的发病率比值（IRR）。
大多数 NCE 产生的估计值大于假设的零，表明存在正残留误差；因此使用了校正后的 p（Cp）值。FQ 暴露后的 IRR 范围为 1.13（95%CI：1.04-1.22-Cp：0.503）至 1.63（95%CI：1.45-1.84-Cp：0.329）。在首次 FQ 暴露前 60 天发现 AAD 事件高峰，在 60 至 30 天和 29 至 1 天的预暴露期间，IRR 增加。目前尚不确定这种 AAD 事件高峰在多大程度上反映了手术后 AAD 矫正后混杂因素的增加或抗生素使用的增加。
本研究未证实先前的研究。使用 Cp 值来解释剩余误差，观察到的 FQ-AAD 关联不能解释为显著。此外，FQ 暴露前 60 天的 AAD 事件激增与指示性混杂一致，或术后抗生素使用增加。
NCT03479736。
