Improving emergency care and outcomes of immune-related adverse events: The immune-related emergency disposition index (IrEDi)

改善紧急护理和免疫相关不良事件的结果：免疫相关紧急处置指数 (IrEDi)

• 批准号: 10351698
• 负责人: Cielito C Reyes-Gibby
• 金额: $ 70.94万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10351698
• 关键词: Accident and Emergency department; Address; Admission activity; Autoimmune Diseases; Binding Sites; Biological; Biological Factors; Biometry; Blood Platelets; Body mass index; C-reactive protein; California; Cancer Center; Cancer Patient; Caring; Chronic; Clinical; Clinical Data; Cohort Studies; Colitis; Collaborations; Comprehensive Cancer Center; Computer software; Data; Data Analyses; Data Collection; Data Sources; Decision Making; Development; Diagnosis; Diagnostic; Diagnostic tests; Dose; Emergency Care; Emergency Department patient; Emergency Medicine; Emergency Situation; Emergency department visit; Emergency research; Epidemiologic Factors; Epidemiology; Erythrocyte Sedimentation Rate; Ethnic Origin; Fibrinogen; Future; Geography; Glucocorticoids; Goals; Gold; Guidelines; Hospitalization; Hour; Image; Immune; Immune checkpoint inhibitor; Immune response; Immunologic Markers; Immunooncology; Inflammation; Laboratories; Length of Stay; Life; Lymphocyte; Medical; Morbidity - disease rate; Neoplasm Metastasis; Ohio; Patient Discharge; Patients; Population Heterogeneity; Process; Prospective cohort study; Publishing; Pulmonary Inflammation; Race; Research; Resources; Sampling; Savings; Severities; Site; Specificity; Standardization; Statistical Models; Symptoms; Telephone; Universities; Visit; base; cancer therapy; cancer type; care outcomes; comorbidity; emergency settings; ethnic difference; follow-up; health record; imaging study; immune checkpoint; immune-related adverse events; improved; indexing; inflammatory marker; inhibitor; innovation; interest; mortality; multidisciplinary; neutrophil; palliating symptoms; patient oriented; patient stratification; predictive marker; predictive tools; prospective; racial and ethnic; recruit; risk stratification; sex; tool

ABSTRACT We respond to Notice of Special Interest: Research in the Emergency Setting, and will build upon the Compre- hensive Oncologic Emergency Research Network (CONCERN). For many cancer patients, Immune Check- point Inhibitors (ICPIs) can be life-saving. However, the immune-related adverse events (irAEs) from ICPIs can be debilitating, and can quickly become severe, or even be fatal. Often irAEs will precipitate visits to the emer- gency department (ED). Therefore, early recognition and the decision to admit, observe or discharge these pa- tients from the ED can be key to a cancer patient’s morbidity and mortality. ED clinicians typically make their decision for disposition (admit, observe or discharge) within 2-6 hours from their patient’s ED presentation. However, irAEs are particularly challenging in the ED because of atypical presentations, the absence of classic symptoms, delayed availability of diagnostic tests during the ED encounter, and the fast pace in the ED setting. At present, there is no single sufficiently large ED data source with clinical, biological, laboratory, and imaging data that will allow for the development of a tool that will guide early recognition and appropriate ED dispo- sition of patients with potential irAEs. Therefore, we propose to capitalize on a multi-site collaboration among 4 CONCERN EDs (MD Anderson Cancer Center, Ohio State University, Northwestern University and University of California San Diego) in different States, to achieve the following aims: 1) To develop a probability model [the Immune-related Emergency Disposition Index (IrEDi)] to risk stratify ED patients on ICPIs for ED disposition. We will leverage our existing data (n=~2000) of unique ED patients who received ICPIs within 3 months of ED presentation at the 4 research sites. We hypothesize that host immune response underlie the development of irAEs and that inflammation/immune biomarkers available during the ED encounter will im- prove the prediction of Hospital admission; Observation; or Discharge, along with traditional factors, i.e. epide- miological factors (age, race/ethnicity), biological factors (sex, BMI), cancer (type, stage/metastases) and treat- ment-related variables (class of ICPI, monotherapy versus combination, dose/duration), and clinical status (comorbidities, preexisting autoimmune diseases, vital signs, laboratory results, imaging study results); and 2) To validate IrEDi using prospective data and determine the predictive validity of irEDi. We will conduct a pro- spective cohort study of ED cancer patients who had received ICPIs, recruiting 1500 total from 4 sites over a 3- year period. A common limitation of ED studies is that patients may receive care from multiple EDs. Thus, we will conduct follow-up calls in 30 days to assess ED revisits or hospitalization. We hypothesize that IrEDi devel- oped in aim 1 will have high sensitivity (≥90%) and high specificity (≥90%) for predicting appropriate ED dispo- sition (hospital admission, observation, or discharge). If our aims are achieved, the IrEDi will be the first risk stratification tool derived from a large racial/ethnically and geographically diverse population of cancer patients. Our future goal is to validate irEDi in general EDs to improve emergency care of cancer patients on ICPIs.

摘要 我们响应特别关注的通知：在紧急情况下的研究，并将建立在压缩， 肿瘤紧急研究网络（CONCERN）。对于许多癌症患者来说，免疫检查- 点抑制剂（ICPIs）可以挽救生命。然而，ICPIs的免疫相关不良事件（irAE）可能 使人衰弱，并可能迅速变得严重，甚至致命。通常，irAE会促使患者前往急诊室就诊， 机构部门（艾德）。因此，早期承认和决定承认，遵守或解除这些条款- 来自艾德的病人可能是癌症病人发病率和死亡率的关键。艾德临床医生通常 在患者出现艾德症状后2-6小时内做出处置决定（入院、观察或出院）。 然而，irAE在艾德中特别具有挑战性，因为非典型表现，缺乏经典的 症状、艾德就诊期间诊断测试的延迟以及艾德环境中的快节奏。 目前，还没有一个足够大的艾德数据源，包括临床、生物学、实验室和成像 这些数据将允许开发一种工具，用于指导早期识别和适当的艾德处置， 发生潜在irAE的患者。因此，我们建议利用多站点协作 在4个关注ED（MD安德森癌症中心，俄亥俄州州立大学，西北大学和 加州圣地亚哥大学）在不同的州，以实现以下目标：1）制定一个概率 模型[免疫相关紧急处置指数（IrEDi）]对接受艾德ICPI治疗的艾德患者进行风险分层 处分我们将利用我们现有的数据（n=~2000），这些数据涉及在3年内接受ICPI的独特艾德患者。 在4个研究中心进行为期数月的艾德演示。我们假设宿主的免疫反应是 irAE的发展以及艾德就诊期间可用的炎症/免疫生物标志物将影响 证明入院、观察或出院的预测，沿着传统因素，即epide- 医学因素（年龄、人种/种族）、生物学因素（性别、BMI）、癌症（类型、分期/转移）和治疗- 心理相关变量（ICPI分类、单药治疗与联合治疗、剂量/持续时间）和临床状态 （合并症、既存自身免疫性疾病、生命体征、实验室结果、成像研究结果）;和2） 使用前瞻性数据验证IrEDi，并确定irEDi的预测有效性。我们将进行一次亲- 在接受ICPI的艾德癌症患者中进行的前瞻性队列研究，在3- 10年内从4个研究中心共招募了1500名患者。 年期间。艾德研究的一个常见局限性是患者可能接受多个ED的护理。因此我们 将在30天内进行电话随访，以评估艾德复诊或住院情况。我们假设IrEDi发展- 在目标1中的选择对于预测适当的艾德分配具有高敏感性（≥90%）和高特异性（≥90%）。 住院（入院、观察或出院）。如果我们的目标实现了，IrEDi将是第一个风险 分层工具来源于大的种族/民族和地理上多样化的癌症患者群体。 我们未来的目标是验证irEDi在一般ED，以改善癌症患者的ICPIs的急诊护理。