Delirium Biomarkers in the Intensive Care Unit

描述（由申请人提供）：谵妄影响重症监护室（ICU）中高达80%的机械通气患者。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。早期识别易受谵妄持续时间延长和更高谵妄严重程度影响的患者将有助于制定有效的治疗干预措施，以减少与谵妄相关的并发症。利用生物标志物来识别易受攻击的谵妄患者的个性化方法易于增加谵妄持续时间和严重程度，这有望减少疾病负担。 该提案描述了一个职业发展计划，该计划将使Khan博士能够通过获得生物标志物技术方面的必要技能， 生物信息学和生物统计学。候选人将在一项大型随机临床试验的背景下研究炎症，星形胶质细胞活化和神经保护的血清生物标志物，谵妄（PMD）试验的药理学管理。Khan博士提出的项目是一项嵌入大型试验的队列研究，受益于R 01的多样化患者人群、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套独特的候选生物标志物谵妄的持续时间和严重程度，并将建立汗博士作为一个神经认知重症监护研究人员。 拟议的职业发展计划包括：a）分子生物学、生物统计学和生物信息学方面的高级课程，B）参加地方/国家会议以发展专业知识 在翻译研究中，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，著名的印第安纳州大学老龄化研究中心，著名的临床和转化科学研究所，以及医学信息学的先驱，Regenstrief研究所。 总的来说，这个职业发展奖将确保必要的保护时间需要推进候选人的职业生涯在生物标志物为基础的转化重症监护研究。此外，该奖项将提供关键支持，以指导未来的翻译研究/R 01应用。未来的研究将评估使用个性化方法的影响，包括通过血清生物标志物结合有效的治疗干预措施早期识别易受伤害的谵妄患者，以降低与ICU谵妄相关的发病率和死亡率。

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.