Can hydroxychloroquine prevent preeclampsia and preterm delivery in lupus pregnancy?

这是斯坦福大学流行病学家朱莉娅·西马德博士R01奖的新申请 大学医学院，作为早期阶段将创新的镜头带到了这个领域 调查员制定研究计划，重点研究患者的不良妊娠结局 系统性红斑狼疮。对于她的K01奖，西马德博士和同事们表明 患有狼疮的孕妇是一个高度用药的群体，她们会经历更多的不良反应 结果，包括早发性先兆子痫、早产、感染和中风。在最近 在试点工作中，Simard博士发现用于治疗狼疮的羟氯喹(HCQ) 在怀孕期间，可以预防先兆子痫和早产。在两个人口中(一个美国 西马德博士还发现，只有不到一半的患有狼疮的孕妇 使用HCQ，尽管有建议。这一点也得到了其他人的证实。 Simard博士在本申请的基础上通过三个大型国际组织 以确定氢氯喹酮是否能降低狼疮患者出现这些不良后果的风险 怀孕。Simard博士将与瑞典、以色列和Kaiser Permanente的同事合作 美国北加州研究部的。这些数据包括以下详细信息 已订购和填写的处方，而且通常没有关于抗磷脂抗体状况的数据 和产次，狼疮生殖研究中的两个关键因素。在目标1中，西马德博士将确定 妊娠期间使用HCQ的妇女是否降低了先兆子痫的风险。在《目标2》中，Dr。 Simard将检查早产，将自发性与医学上的指征分开，以 检查子痫前期的总体风险和用药情况，以及糖皮质激素等其他因素 使用和妊娠期糖尿病。 在Aim 3中，Simard博士的团队将确定孕妇使用HCQ的障碍和促进剂 与狼疮采用一种创新的混合方法设计。在评估患者的依从性和 美国和以色列大型数据库中临床医生遵守指南的情况，他们将确定 不太可能粘连的亚群，检查它们与粘连患者的不同之处。然后 与患者和提供者合作，他们将使用这些量化结果来识别 使用Focus从患者和提供者的角度分析遵守规则的障碍和促进者 组。这一目标将提供有关HCQ使用和处方实践的关键信息，以改进 分析范式和我们对HCQ在狼疮妊娠中使用的临床理解，以及 为临床护理和可能的未来临床试验提供基础支持。

This is a new application for an R01 award for epidemiologist Dr. Julia Simard, at Stanford University School of Medicine, who brings an innovative lens to the field as an early stage investigator building a research program focused on adverse pregnancy outcomes in patients with systemic lupus erythematosus. For her K01 award, Dr. Simard and colleagues showed that pregnant women with lupus are a highly-medicated group, who experience more adverse outcomes, including early-onset preeclampsia, preterm delivery, infection, and stroke. In recent pilot work, Dr. Simard found that hydroxychloroquine (HCQ), which is used to manage lupus during pregnancy, may prevent preeclampsia and preterm delivery. In two populations (one US and one in Sweden), Dr. Simard also found that fewer than half of pregnant women with lupus use HCQ, despite recommendations. This has been corroborated by others as well. Dr. Simard builds upon this work in the present application via three large international populations to determine whether HCQ reduces the risk of these adverse outcomes in lupus pregnancies. Dr. Simard will partner with colleagues in Sweden, Israel, and Kaiser Permanente of Northern California’s Division of Research in the United States. These data include details on ordered and filled prescriptions, and often unavailable data on antiphospholipid antibody status and parity, two critical factors in lupus reproductive research. In aim 1, Dr. Simard will determine whether preeclampsia risk is reduced in women who use HCQ during pregnancy. In aim 2, Dr. Simard will examine preterm delivery, partitioning spontaneous from medically-indicated, to examine overall risks and medication by preeclampsia and other factors such as glucocorticoid use and gestational diabetes. In aim 3, Dr. Simard’s team will identify barriers and facilitators of HCQ use in pregnant women with lupus using an innovative mixed methods design. After evaluating patient adherence and guideline adherence by clinicians in the large US and Israeli databases, they will identify subsets less likely to adhere and examine how they differ from adherent patients. Then partnering with patients and providers, they will use these quantitative findings to identify barriers and facilitators of adherence from the patient and provider perspectives using focus groups. This aim will provide key information on HCQ use and prescription practices to improve the analytic paradigm and inform our clinical understanding HCQ use in lupus pregnancy, and provide foundational support for clinical care and possibly, a future clinical trial.