Informing the Emergency Care of Septic Shock Patients: A Novel Application of Data-Driven Analytics

项目总结 背景：感染性休克是一种常见的、代价高昂的致命疾病。人们越来越认识到 感染性休克患者在(1)临床表现、(2)对治疗的反应和(3)方面存在显著差异。 临床结果。这种患者水平的异质性可能解释了为什么最佳的早期感染性休克治疗 人们对此仍然知之甚少。感染性休克患者死亡的可能性是感染性休克患者的四倍 没有受到惊吓。我们的初步数据显示，黑人患者死于感染性休克的几率更高 与白人患者相比。目前的研究没有描述感染性休克患者的异质性。 患者和没有解释可能影响结果差异的药物遗传因素。 目标：需要从协同数据类型中获得见解，以便更全面地了解 感染性休克的异质性和可能影响血管升压反应和差异的遗传因素 结果。拟议研究的总体目标是确定表型和遗传的特征。 感染性休克的异质性方面。这项工作分为两个目标：(1)确定感染性休克 用先进的分析方法进行表型分析和(2)血管升压药的药效学定量 种族和血管加压反应的多态。我们的总体假设是高级分析 应用于临床和遗传数据的方法可以识别感染性休克异质性的定义特征， 与急诊科早期感染性休克处理和预后差异有关。 方法：(目标1)我们将使用一个全国性的低血压难治性败血症患者数据集。 急诊科液体复苏和应用无监督机器学习聚类方法 明确感染性休克早期患者的临床相关表型。我们将分析表型变异在 临床特点和转归。然后，我们将开发一个用于表型分类的监督模型。 (目标2)我们将对100个样本进行有针对性的药物基因组学检测，其中73个样本是RACE的一部分 来自我们城市安全网医院的感染性休克患者的现有研究生物库。我们将招收一名 另外27名患者完成样本。我们将检查单核苷酸风险等位基因的存在 血管加压素相关基因的种族多态。我们还将研究两者之间的关联 有针对性的遗传多态和电击逆转。 职业发展：在拟议的职业发展奖期间，我将与我的指导团队合作 建立必要的技能，以实现作为临床研究人员的独立性。具体地说，我将1)收到 具有设计和实施转化性临床研究研究的实践经验，2)接受指导 数据科学、生物医学信息学和实施科学的课程工作，3)接受培训和 翻译数据科学、临床决策支持、药物基因组学和精确公共领域的教育 健康，以及4)成为学术急救医学的领导者和有效导师。

PROJECT SUMMARY Background: Septic shock is a commonly, costly, and deadly condition. There is increasing recognition that septic shock patients vary significantly in terms of (1) clinical presentation, (2) response to treatments, and (3) clinical outcomes. This patient-level heterogeneity may explain why optimal early septic shock management remains poorly understood. Patients with septic shock are four times more likely to die than septic patients without shock. Our preliminary data shows that Black patients have higher odds of mortality from septic shock compared to White patients. Current studies do not characterize patient heterogeneity among septic shock patients and do not explicate pharmacogenetic factors that may influence disparities in outcomes. Objective: Insights from synergistic data types are necessary to provide a more complete understanding of septic shock heterogeneity and hereditable factors that may influence vasopressor response and disparities in outcomes. The overall objective of the proposed research is to characterize both phenotypic and genetic aspects of heterogeneity in septic shock. This work is organized into two aims: (1) Identify Septic Shock Phenotypes Using Advanced Analytic Methods and (2) Quantify Vasopressor Pharmacogenetic Polymorphisms by Race and Vasopressor Response. Our overall hypothesis is that advanced analytic methods applied to clinical and genetic data can identify defining features of septic shock heterogeneity that are relevant to early septic shock management in the Emergency Department and disparities in outcomes. Methods: (Aim 1) We will use a national dataset of septic patients with hypotension refractory to initial Emergency Department fluid resuscitation and apply unsupervised machine learning clustering methods to define clinically relevant phenotypes of early septic shock patients. We will analyze phenotypic variation in clinical characteristics and outcomes. Then, we will develop a supervised model for phenotype classification. (Aim 2) We will perform targeted pharmacogenomics of 100 samples balanced for race, 73 of which are part of an existing research biobank of septic shock patients from our urban, safety-net hospital. We will enroll an additional 27 patients to complete the sample. We will examine the presence of risk alleles of single nucleotide polymorphisms for vasopressor-relevant genes by race. We will also examine the association between the targeted genetic polymorphisms and shock reversal. Career Development: During the proposed Career Development Award, I will work with my mentorship team to build the skills necessary to achieve independence as a clinical researcher. Specifically, I will 1) receive hands-on experience in the design and conduct of translational clinical research studies, 2) take didactic coursework in data science, biomedical informatics, and implementation science, 3) receive training and education in translational data science, clinical decision support, pharmacogenomics, and precision public health, and 4) become a leader and an effective mentor in academic emergency medicine.