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《等待戈多》:基于横断面调查的印度羟氯喹预防新冠病毒策略分析

Waiting for Godot: A cross sectional survey based analysis of the hydroxychloroquine prophylaxis strategy against COVID-19 in India.

作者信息

Moni Merlin, Madathil Thushara, Palabatla Rahul, Balachandran Sabarish, Edathadathil Fabia, Gutjahr Georg, Madathil Sai B, Pai Rajesh, Kv Beena, Jayant Aveek, Sathyapalan Dipu T

机构信息

Department of General Medicine and Division of Infectious Diseases, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala.

Department of Anaesthesiology and Critical Care Medicine, Amrita Institute of Medical Sciences and Research Centre, Kochi, Kerala.

出版信息

J Public Health Res. 2020 Dec 30;9(4):1888. doi: 10.4081/jphr.2020.1888. eCollection 2020 Oct 14.

DOI:10.4081/jphr.2020.1888
PMID:33457350
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7802012/
Abstract

India currently has the second largest burden of infections due to COVID-19. Health Care Worker (HCW) shortages are endemic to Indian healthcare. It should therefore be a huge priority to protect this precious resource as a critical component of the systemic response to this pandemic. Advisories from the Indian Council of Medical Research (ICMR) have focused on using hydroxychloroquine prophylaxis against COVID-19 in at risk HCW. This prophylaxis strategy has no evidence. In further jeopardy there appear to insubstantial attempts to build this evidence as well. In this connection, we commissioned a survey within our Institution to estimate the penetration of hydroxychloroquine (HCQ) use and use this to statistically model the impact of current ongoing studies in India. We also briefly review the literature on HCQ prophylaxis for COVID-19. A structured survey designed using RedCAP application was disseminated among healthcare professionals employed at an academic referral tertiary care centre via online social media platforms. The survey was kept open for the entire month of June 2020. The survey was additionally used to statistically model the size of studies required to comprehensively address the efficacy of HCQ in this setting. 522 responses were received, of which 4 were incomplete. The ICMR strategy of 4 or more doses of HCQ was complete only in 15% of HCW in our survey. The majority of respondents were doctors (238, 46%). Amongst all category of responders, only 12% (n=63) received the full course. A majority of those who initiated the chemoprophylaxis with HCQ turned out to be medical professionals (59/63) with neither nurse nor other categories of healthcare workers accessing the medication. The respondents of our institutional survey did not report any life-threatening side effects. Presuming efficacy as per ICMR modelling for new registry trial on the lines of the published case control study, equal allocation between cases and controls and assuming a RR of 1.3.6, the power of such a study would be very low for n=2000 for event rates from 2.5-12.5%. We report the low penetration of HCQ chemoprophylaxis among the healthcare workers of our institution. We highlight the inherent drawbacks in the study design of current national COVID related trial based on the statistical modelling of our survey results and published literature, and thereby emphasis the need of evidence-based strategies contributing to research policy at national level.

摘要

印度目前是因新冠病毒感染而负担第二重的国家。医护人员短缺是印度医疗体系的痼疾。因此,将这一宝贵资源作为应对这场大流行的系统性应对措施的关键组成部分加以保护,应成为重中之重。印度医学研究理事会(ICMR)的咨询意见聚焦于让有风险的医护人员使用羟氯喹预防新冠病毒。这一预防策略并无证据支持。此外,似乎也没有实质性的努力来获取这方面的证据。在此背景下,我们在本机构内开展了一项调查,以估计羟氯喹(HCQ)的使用普及率,并据此对印度正在进行的研究的影响进行统计建模。我们还简要回顾了关于使用HCQ预防新冠病毒的文献。一项使用RedCAP应用程序设计的结构化调查通过在线社交媒体平台在一家学术转诊三级护理中心工作的医护人员中进行传播。该调查在2020年6月整月开放。该调查还被用于对全面评估HCQ在此情况下疗效所需研究规模进行统计建模。共收到522份回复,其中4份不完整。在我们的调查中,ICMR提出的4剂或更多剂HCQ的策略在仅15%的医护人员中得到落实。大多数受访者是医生(238人,占46%)。在所有类别的受访者中,只有12%(n = 63)接受了完整疗程。大多数开始使用HCQ进行化学预防的人是医学专业人员(59/63),护士和其他类别的医护人员均未使用该药物。我们机构调查的受访者未报告任何危及生命的副作用。假设按照ICMR针对已发表病例对照研究进行新注册试验的模型计算疗效,病例与对照平均分配,并假设相对危险度为1.3.6,对于事件发生率在2.5 - 12.5%之间、样本量n = 2000的此类研究,检验效能将非常低。我们报告了HCQ化学预防在我们机构医护人员中的低普及率。基于我们的调查结果和已发表文献的统计建模,我们强调了当前国家新冠相关试验研究设计中固有的缺陷,从而强调了基于证据的策略对国家层面研究政策的重要性。

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本文引用的文献

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Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).COVID-19 住院患者使用羟氯喹(无论是否联合使用阿奇霉素)导致 QT 间期延长的风险。
JAMA Cardiol. 2020 Sep 1;5(9):1036-1041. doi: 10.1001/jamacardio.2020.1834.
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Hydroxychloroquine plus personal protective equipment versus standard personal protective equipment alone for the prevention of COVID-19 infections among frontline healthcare workers: the HydrOxychloroquine Prophylaxis Evaluation(HOPE) trial: A structured summary of a study protocol for a randomized controlled trial.羟氯喹联合个人防护装备与单纯标准个人防护装备用于预防一线医护人员 COVID-19 感染的效果比较:羟氯喹预防评估(HOPE)试验:一项随机对照试验研究方案的结构化总结。
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3
Which QTc correction formulae (Bazett, Framingham, or Fridericia) to use for Hydroxychloroquine induced QTc prolongation?对于羟氯喹诱导的QTc延长,应使用哪种QTc校正公式(巴泽特公式、弗雷明汉姆公式还是弗里德里西亚公式)?
Indian Pacing Electrophysiol J. 2020 Sep-Oct;20(5):208. doi: 10.1016/j.ipej.2020.06.008. Epub 2020 Jul 1.
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Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19.医护人员与 SARS-CoV-2 在印度的感染:COVID-19 时期的病例对照研究。
Indian J Med Res. 2020 May;151(5):459-467. doi: 10.4103/ijmr.IJMR_2234_20.
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Prevalence of Flu-like Symptoms and COVID-19 in Healthcare Workers from India.印度医护人员中流感样症状和新冠病毒病的患病率
J Assoc Physicians India. 2020 Jul;68(7):27-29.
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A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.羟氯喹作为 COVID-19 暴露后预防的随机试验。
N Engl J Med. 2020 Aug 6;383(6):517-525. doi: 10.1056/NEJMoa2016638. Epub 2020 Jun 3.
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Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review.羟氯喹或氯喹治疗或预防 COVID-19:一项实时系统评价。
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Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data.羟氯喹治疗需要吸氧的 COVID-19 肺炎患者的临床疗效:利用常规护理数据进行的观察性对比研究。
BMJ. 2020 May 14;369:m1844. doi: 10.1136/bmj.m1844.