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多潘立酮增加帕金森病的有害心脏事件:一项观察性研究的贝叶斯再分析。

Domperidone increases harmful cardiac events in Parkinson's disease: A Bayesian re-analysis of an observational study.

机构信息

CHUM Research Center, Pavillon S, 850, St-Denis St., Montreal, Quebec, Canada; The Canadian Network for Observational Drug Effect Studies (CNODES), Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine H-485, Montreal, Quebec Canada; University of Montreal, 2900 Edouard Montpetit Blvd, Montreal, Quebec Canada.

Department of Medicine, McGill University, 3605 de la Montagne St., Montreal, Quebec Canada; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1020 Pine Ave W, Montreal, Quebec Canada.

出版信息

J Clin Epidemiol. 2021 Dec;140:93-100. doi: 10.1016/j.jclinepi.2021.09.002. Epub 2021 Sep 8.

Abstract

OBJECTIVES

To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson's disease (PD).

STUDY DESIGNS AND SETTINGS

Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors' strengths, different priors, and Bayesian meta-analysis RESULTS: The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively.

CONCLUSION

While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses.

摘要

目的

评估多潘立酮在帕金森病(PD)患者中的室性心动过速/心源性猝死(VT/SCD)风险。

研究设计和设置

使用贝叶斯方法,将观察性研究的结果与先验信念相结合,计算与不使用相比,多潘立酮使用时 VT/SCD 的相对风险(RR)增加的后验概率(RR)和危害,定义为风险超过 15%。使用正态分布先验(RR(对数))进行分析:无信息(N(0,10))或信息(N(0.53,179)),来自荟萃分析(OR(95%CI):1.70(1.47-1.97))。进行了敏感性分析:不同先验的强度、不同的先验和贝叶斯荟萃分析。

结果

无信息先验产生的 RR:1.23(95%置信区间(CrI):0.94-1.62),与已发表的频率 RR 相似:1.22(95%CI:0.99-1.50),危害的可能性为 69%。使用权重为 100%、50%和 10%的信息先验,RR 分别为 1.63(1.41-1.88)、1.57(1.31-1.91)和 1.39(1.10-1.93)。相应的危害概率分别为 100%、99%和 94%。

结论

虽然基于无信息先验的频率和贝叶斯方法都无法对多潘立酮在 PD 患者中的心律失常风险得出明确结论,但具有信息先验的贝叶斯分析显示,风险增加的可能性很高,对多种先验敏感性分析具有稳健性。

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