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

通知感染性休克患者的紧急护理：数据驱动分析的新应用

• 批准号: 10491283
• 负责人: Lauren Page Black
• 金额: $ 18.01万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10491283
• 关键词: ADRB2 gene; Accident and Emergency department; Address; Area; Black race; Blood Pressure; Blood specimen; Characteristics; Classification; Clinical; Clinical Data; Clinical Research; Conflict (Psychology); Critical Care; Critical Illness; Data; Data Science; Data Set; Electronic Health Record; Emergency Care; Emergency Department patient; Emergency Medicine; Emergency Situation; Enrollment; Funding; Genes; Genetic; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Heritability; Heterogeneity; Hospitals; Hour; Human; Hypotension; IV Fluid; Intervention; K-Series Research Career Programs; Knowledge; Lead; Liquid substance; Medical Genetics; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Modeling; National Institute of General Medical Sciences; Outcome; Patients; Performance; Persons; Pharmaceutical Preparations; Pharmacogenetics; Pharmacogenomics; Phenotype; Population; Public Health; Race; Refractory; Research; Research Personnel; Resuscitation; Sampling; Scientist; Sepsis; Septic Shock; Shock; Single Nucleotide Polymorphism; Socioeconomic Status; Subgroup; Supervision; Systemic infection; Time; Training; Training and Education; Underrepresented Populations; Undifferentiated; Variant; Vasoconstrictor Agents; Work; advanced analytics; analytical method; base; beta-adrenergic receptor; biobank; biomedical informatics; black patient; blood pressure elevation; career; career development; clinical decision support; clinically relevant; cohort; cost; deep learning model; design; experience; implementation science; improved; innovation; insight; mortality; multidisciplinary; novel; patient population; patient response; premature; prospective; racial disparity; research study; response; risk variant; safety net; septic patients; skills; social factors; social health determinants; supervised learning; translational physician; treatment response; unsupervised learning

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.

项目摘要 背景：败血性休克通常是一种通常，昂贵且致命的状况。人们越来越认识到 （1）临床表现，（2）对治疗的反应和（3）的败血性休克患者在（1）临床表现方面有显着差异。 临床结果。这种患者级异质性可以解释为什么最佳的早期败血性冲击管理 仍然很了解。败血性休克患者死亡的可能性是化粪池患者的四倍 没有震惊。我们的初步数据表明，黑人患者因败血性休克的死亡率较高 与白人患者相比。当前的研究未表征化粪池休克之间患者的异质性 患者并且不阐明可能影响结果差异的药物遗传因素。 目的：必须从协同数据类型的见解来提供对更完整的了解 败血性休克异质性和可遗传性因素可能影响加压剂反应和差异 结果。拟议研究的总体目的是表征表型和遗传 败血性休克中异质性的各个方面。这项工作分为两个目的：（1）确定败血性冲击 使用先进的分析方法和（2）定量加速器药物遗传学的表型 种族和升压器反应的多态性。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败血性休克异质性的定义特征 与急诊室的早期败血性冲击管理有关，结果差异。 方法：（ AIM 1）我们将使用抗耐受性的化粪池患者的国家数据集来初始 急诊部的流体复苏，并将无监督的机器学习聚类方法应用于 定义早期败血性休克患者的临床相关表型。我们将分析表型变化 临床特征和结果。然后，我们将开发一个用于表型分类的监督模型。 （AIM 2）我们将执行针对种族平衡的100个样品的有针对性的药物基因组学，其中73个是 来自我们城市安全网络医院的化粪池休克患者的现有研究生物库。我们将注册 另外27名患者可以完成样本。我们将检查单核苷酸的风险等位基因的存在 种族相关基因的多态性基因。我们还将研究 靶向遗传多态性和冲击逆转。 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 建立成为临床研究人员独立所必需的技能。具体来说，我将1）收到 翻译临床研究的设计和行为实践经验，2） 数据科学，生物医学信息学和实施科学课程，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众的教育 健康和4）成为学术急诊医学领域的领导者和有效的导师。