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

项目摘要 候选人：我的长期职业目标是成为一名独立的、以病人为导向的研究人员， 通过调查问题和制定干预措施， 睡眠生理学、昼夜节律生物学和危重疾病的交叉点。我的K23相关职业发展 这些活动将使我能够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、谵妄和更广泛的危重患者的相关影响 疾病的结果。我接受过重症监护和睡眠医学的相关临床培训。我有了耐心- 通过进行几项与ICU睡眠中断相关的研究，获得了面向研究的经验。我的K23奖 包括昼夜节律生物学的职业发展培训，重点是（1）昼夜节律测量，（2） 昼夜节律干预;（3）纵向数据分析。完成这些培训活动将 弥合知识差距，并建立未来的成功作为一个独立的调查。 导师和环境：我的导师是亨利·克拉·雅吉博士、玛格丽特·皮萨尼博士和南希·雷德克尔博士， 一组经验丰富，致力于睡眠医学，重症监护医学，昼夜节律等领域的专家 测量、ICU谵妄和以患者为导向的研究。这个团队已经展示了合作的成功， 每个成员都有自己独特的专长我还与顾问肯尼思赖特博士（昼夜节律生物学 Terrence Murphy博士（分析专家）。我的系主任（加里德西尔博士）和科 纳夫塔利·卡明斯基博士保证，我将继续把至少75%的时间用于 职业发展活动。我们将从耶鲁-纽黑文医院医学ICU招募研究对象 这是一个高容量的重症监护室，有足够的病人使这个项目可行。我们部门的翻译 研究中心将支持该项目。 指导研究项目：谵妄影响50-80%的内科ICU患者。预防和治疗 治疗策略有限，谵妄与不良结局相关，包括死亡率增加。因为重症监护室 睡眠中断可能是ICU谵妄发生的一个因素，建议促进睡眠 治疗和预防谵妄目前，缺乏对潜在的 昼夜节律异常对ICU睡眠中断和随之而来的谵妄问题的重要贡献。 昼夜节律异常可能是可改变的，因此构成了ICU谵妄的新治疗靶点。 本项目将前瞻性研究ICU患者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，并检查昼夜节律异常与 精神错乱的日子此外，我们会进行一项随机对照试验，以评估 为ICU患者提供白天明亮的光线，以促进昼夜节律。

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. My K23-related career development activities 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 patient- oriented research experience by conducting several studies related to sleep disruption in the ICU. My K23 award includes career development 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 knowledge gaps and set up future success as an independent investigator. Mentors and Environment: I am 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 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 continue to 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 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 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 to assess the feasibility of providing daytime bright light to ICU patients to promote circadian entrainment.