Delirium Biomarkers in the Intensive Care Unit

重症监护病房中的谵妄生物标志物

• 批准号: 8424119
• 负责人: Babar A Khan
• 金额: $ 12.77万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424119
• 关键词: Affect; Aging; Astrocytes; Attention; Award; Bioinformatics; Biological Assay; Biological Markers; Biological Process; Biometry; Blood; Blood specimen; C-reactive protein; Clinical Investigator; Clinical Research; Clinical Sciences; Clinical Trials; Cohort Studies; Complement; Complex; Coupled; Critical Care; Critical Illness; Data; Delirium; Development; Development Plans; Dexmedetomidine; Disease; Early identification; Enrollment; Ensure; Environment; Funding; Future; Growth Factor; Hospitals; IL8 gene; Indiana; Inflammation; Institutes; Insulin-Like Growth Factor I; Intensive Care Units; Interleukin-1; Interleukin-6; Intervention; K-Series Research Career Programs; Measures; Medical Informatics; Mentors; Molecular; Molecular Biology; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Neurocognitive; Nonlinear Dynamics; Occupational; Pathologic; Patients; Protocols documentation; Randomized Clinical Trials; Research; Research Infrastructure; Research Personnel; Resources; Role; Sampling; Serum; Severities; Structure; Study of serum; Symptoms; System; TNF gene; Technology; Therapeutic Intervention; Therapeutic Studies; Time; Training; Translational Research; United States National Institutes of Health; Universities; Variant; Work; base; burden of illness; career; career development; clinical phenotype; data acquisition; didactic education; effective therapy; experience; inflammatory marker; insight; meetings; mortality; multidisciplinary; neuroprotection; patient oriented; patient population; skills; translational study

DESCRIPTION (provided by applicant): Delirium affects up to 80% of mechanically ventilated patients in the intensive care unit (ICU). Delirium duration and severity are independently associated with higher morbidity and mortality. Early identification of patients susceptible to prolonged delirium duration and higher delirium severity will help in instituting effective therapeutic interventions to reduce complications associated with delirium. A personalized approach utilizing biomarkers to identify vulnerable delirious patients prone to increased delirium duration and severity offers promise to curtail the disease burden. This proposal describes a career development plan that will enable Dr. Khan to develop expertise in patient-oriented translational clinical research by acquiring the necessary skills in biomarker technology, bio- informatics and biostatistics. The candidate will study serum biomarkers of inflammation, astrocyte activation and neuroprotection in the context of a large randomized clinical trial, the Pharmacological Management of Delirium (PMD) trial. Dr. Khan's proposed project is a cohort study embedded within the large trial benefiting from the diverse patient population, data acquisition resources, research personnel and other inherent strengths of an R01. The completion of the project will identify a unique set of candidate biomarkers for delirium duration and severity and will establish Dr. Khan as a neurocognitive critical care researcher. The proposed career development plan integrates; a) advanced coursework in molecular biology, biostatistics, and bioinformatics, b) participation in local/national meetings to develop expertise in translational research, c) a multidisciplinary mentored research experience, and d) a highly supportive research environment. This environment includes an internationally recognized NIH funded PMD Study Group, a distinguished Indiana University Center for Aging Research, a renowned Clinical and Translational Sciences Institute, and pioneers in Medical Informatics, the Regenstrief Institute. Overall, this career development award will ensure the necessary protected time required to advance the candidate's career in biomarker based translational critical care research. In addition, the award will provide critical support to guide future translational studies / R01 applications. Future studies will assess the impact of utilizing a personalized approach consisting of early identification of vulnerable delirious patients through serum biomarkers coupled with effective therapeutic interventions in decreasing the morbidity and mortality associated with ICU delirium. PUBLIC HEALTH RELEVANCE: Project Narrative: A significant majority of critically ill patients admitted to the intensive care unit suffers from delirium with both delirium duration and its severity contributing independently to patient's morbidity and mortality. A current role of biomarkers to identify patients prone to prolonged delirium duration and higher severity is uncertain. This project seeks to develop a personalized approach of managing delirium by identifying candidate biomarkers that can prognosticate delirium duration and severity.

描述（由申请人提供）：重症监护病房 (ICU) 中多达 80% 的机械通气患者患有谵妄。谵妄持续时间和严重程度与较高的发病率和死亡率独立相关。早期识别容易出现谵妄持续时间延长和谵妄严重程度较高的患者将有助于采取有效的治疗干预措施，以减少与谵妄相关的并发症。利用生物标记物来识别易受谵妄持续时间和严重程度增加的易受伤害的谵妄患者的个性化方法有望减少疾病负担。 该提案描述了一项职业发展计划，该计划将使汗博士能够通过获得生物标志物技术的必要技能来发展以患者为导向的转化临床研究的专业知识， 生物信息学和生物统计学。候选人将在大型随机临床试验谵妄药理学管理 (PMD) 试验的背景下研究炎症、星形胶质细胞激活和神经保护的血清生物标志物。 Khan 博士提议的项目是一项嵌入大型试验中的队列研究，受益于 R01 的多样化患者群体、数据采集资源、研究人员和其他固有优势。该项目的完成将确定一组独特的谵妄持续时间和严重程度的候选生物标志物，并将汗博士确立为神经认知重症监护研究员。 拟议的职业发展计划整合了； a) 分子生物学、生物统计学和生物信息学的高级课程，b) 参加地方/国家会议以发展专业知识 在转化研究中，c）多学科指导的研究经验，以及 d）高度支持的研究环境。这个环境包括国际公认的 NIH 资助的 PMD 研究小组、著名的印第安纳大学衰老研究中心、著名的临床和转化科学研究所以及医学信息学先驱 Regenstrief 研究所。 总体而言，该职业发展奖将确保候选人在基于生物标志物的转化重症监护研究中推进职业生涯所需的必要受保护时间。此外，该奖项将为指导未来的转化研究/R01应用提供关键支持。未来的研究将评估采用个性化方法的影响，包括通过血清生物标志物早期识别易受伤害的谵妄患者，并结合有效的治疗干预措施，以降低 ICU 谵妄相关的发病率和死亡率。 公共健康相关性：项目叙述：绝大多数入住重症监护病房的危重患者患有谵妄，谵妄持续时间及其严重程度独立影响患者的发病率和死亡率。目前生物标志物在识别容易出现谵妄持续时间延长和严重程度较高的患者方面的作用尚不确定。该项目旨在通过识别可预测谵妄持续时间和严重程度的候选生物标志物来开发治疗谵妄的个性化方法。