Circadian Rhythm as a Novel Therapeutic Target in the Intensive Care Unit

项目总结 应聘者：我的长期职业目标是成为一名独立的、以病人为中心的研究人员，并将不断改进 重症监护病房(ICU)通过调查问题和制定干预措施的结果 睡眠生理学、昼夜生物学和危重疾病的交叉学科。我提出了职业发展的建议 这些活动将使我做好准备，成功地进行一系列调查，重点是了解ICU 昼夜节律异常及其对ICU睡眠中断、精神错乱和更广泛的影响 危重疾病结局。我接受过重症监护和睡眠医学方面的相关临床培训。我得到了首字母 通过在ICU进行几项与睡眠中断有关的研究，获得了以患者为导向的研究经验。在……里面 在这个K23应用程序中，我建议对昼夜节律进行专门的培训，重点是(1)昼夜节律 测量，(2)昼夜夹带干预，和(3)纵向数据分析。完成这些工作 培训活动将弥合目前的知识差距，并为今后作为独立调查员取得成功奠定基础。 导师和环境：我将得到亨利·克拉尔·亚吉、玛格丽特·皮萨尼和南希博士的指导 Redeker是一支经验丰富、专注于睡眠医学、重症监护医学、 昼夜节律测量、ICU精神错乱和以病人为中心的研究。这个团队已经证明了 合作成功，每个成员都带来了独特的专业知识。我还将与顾问Kenneth博士合作 赖特(昼夜生物专家)和特伦斯·墨菲博士(分析专家)。我的部门主任(Dr。 加里·德希尔)和科长(纳夫塔利·卡明斯基博士)提供了保证，我将至少致力于75% 把我的时间用来从事职业发展活动。我们将从耶鲁-纽黑文医院招募研究对象 医疗ICU，这是一个大容量的ICU，有足够的病人使这个项目可行。我们这个部门的 翻译研究核心和医学ICU生物库将支持这一项目。 指导研究项目：精神错乱影响50%-80%的内科ICU患者。预防和治疗 策略是有限的，精神错乱与包括增加死亡率在内的不良结局有关。因为 ICU睡眠中断可能是导致ICU精神错乱发展的一个因素，睡眠促进是 推荐用于治疗和预防精神错乱。目前，对这一事件缺乏调查 昼夜节律异常对ICU睡眠中断问题的潜在重大贡献 随之而来的精神错乱。昼夜节律异常是潜在的可改变的，因此构成了一种新的治疗方法 ICU精神错乱的目标。该项目将前瞻性地研究ICU患者(N=100)的详细昼夜节律 措施。我们将研究ICU光照水平对昼夜节律异常的影响，并研究 昼夜节律异常与精神错乱天数的关系。此外，我们还将进行一项试点 随机对照试验(N=50)，以评估向ICU患者提供日间强光的可行性 促进昼夜节律夹带。

PROJECT SUMMARY Candidate: My long-term career goal is to be an independent patient-oriented researcher who will improve outcomes in the intensive care unit (ICU) by investigating questions and developing interventions at the intersection of sleep physiology, circadian biology, and critical illness. I have proposed career development activities that will prepare me to successfully conduct a series of investigations focused on understanding ICU circadian rhythm abnormalities and the associated effects on ICU sleep disruption, delirium, and broader critical illness outcomes. I have relevant clinical training in critical care and sleep medicine. I have gained initial patient-oriented research experience by conducting several studies related to sleep disruption in the ICU. In this K23 application, I am proposing specific training in circadian biology with a focus on (1) circadian rhythm measurement, (2) circadian entrainment interventions, and (3) longitudinal data analysis. Completion of these training activities will bridge current knowledge gaps and set up future success as an independent investigator. Mentors and Environment: I will be mentored by Drs. Henry Klar Yaggi, Margaret Pisani, and Nancy Redeker, a team of experienced, committed experts in the fields of sleep medicine, critical care medicine, circadian measurement, ICU delirium, and patient-oriented research. This team has demonstrated collaborative success, and each member brings unique expertise. I will also work with advisors Dr. Kenneth Wright (circadian biology expert) and Dr. Terrence Murphy (analytics expert). My department Chairperson (Dr. Gary Desir) and Section Chief (Dr. Naftali Kaminski) have provided assurance that I will dedicate at least 75% of my time to career development activities. We will recruit study subjects from the Yale-New Haven Hospital Medical ICU which is a high volume ICU with sufficient patients to make this project feasible. Our section's Translational Research Core and Medical ICU Biorepository will support this project. Mentored Research Project: Delirium affects 50-80% of medical ICU patients. Prevention and treatment strategies are limited, and delirium is associated with poor outcomes including increased mortality. Because ICU sleep disruption is likely to be a contributor to the development of ICU delirium, sleep promotion is recommended for delirium treatment and prevention. Currently, there is a lack of investigation regarding the potentially significant contribution of circadian abnormalities to the problem of ICU sleep disruption and consequent delirium. Circadian abnormalities are potentially modifiable, and thus constitute a novel therapeutic target for ICU delirium. This project will prospectively study ICU patients (N=100) with detailed circadian measures. We will examine the impact of ICU light levels on circadian abnormalities and examine the association between circadian abnormalities and days of delirium. In addition, we will conduct a pilot randomized controlled trial (N=50) to assess the feasibility of providing daytime bright light to ICU patients to promote circadian entrainment.