Delirium Biomarkers in the Intensive Care Unit

描述(由申请人提供)：在重症监护病房(ICU)中，高达80%的机械通气患者会出现精神错乱。精神错乱的持续时间和严重程度与较高的发病率和死亡率独立相关。及早识别易患持续时间延长和严重程度较高的患者，将有助于制定有效的治疗干预措施，以减少与妄想相关的并发症。一种个性化的方法，利用生物标记物来识别易受伤害的精神错乱患者，容易增加精神错乱的持续时间和严重程度，这提供了减少疾病负担的希望。这份提案描述了一项职业发展计划，该计划将使可汗博士能够通过获得生物标记物技术方面的必要技能，在面向患者的转化性临床研究方面发展专业知识。 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、星形胶质细胞激活和神经保护的血清生物标记物，即Delirium的药物管理(PMD)试验。Khan博士提出的项目是一项嵌入大型试验的队列研究，受益于多样化的患者群体、数据获取资源、研究人员和R01的其他固有优势。该项目的完成将确定一组独特的用于衡量精神错乱持续时间和严重程度的候选生物标记物，并将确立可汗博士作为神经认知重症监护研究员的地位。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/国家会议以发展专门知识。 在翻译研究方面，c)多学科指导的研究经验，d)高度支持性的研究环境。这种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老龄研究中心，著名的临床和翻译科学研究所，以及医学信息学的先驱Regenstrief研究所。总体而言，这一职业发展奖将确保必要的保护时间，以促进候选人在基于生物标记物的转化性危重护理研究中的职业生涯。此外，该奖项将为指导未来的翻译研究/R01申请提供关键支持。未来的研究将评估利用个性化方法的影响，该方法包括通过血清生物标记物早期识别脆弱的精神错乱患者，并辅之以有效的治疗干预措施，以降低与ICU精神错乱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.