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

昼夜节律作为重症监护病房的新型治疗目标

• 批准号: 10438282
• 负责人: MELISSA P KNAUERT
• 金额: $ 4.64万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-09 至 2022-03-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10438282
• 关键词: Affect; Biology; Chairperson; Circadian Dysregulation; Circadian Rhythms; Critical Care; Critical Illness; Data Analyses; Delirium; Development; Environment; Future; Goals; Hospitalization; Hospitals; Intensive Care Units; Intervention; Investigation; Knowledge; Light; Measurement; Measures; Medical; Medicine; Mentored Patient-Oriented Research Career Development Award; Mentors; Outcome; Patients; Prevention; Prevention strategy; Prospective Studies; Randomized Controlled Trials; Research Personnel; Research Project Grants; Series; Sleep; Sleep disturbances; Study Subject; Time; Training; Training Activity; Translational Research; Work; career; career development; circadian; clinically relevant; experience; improved; improved outcome; member; mortality; new therapeutic target; patient oriented; patient oriented research; prevent; recruit; sleep physiology; success; treatment strategy

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.

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。我与K23相关的职业发展 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、精神错乱和更广泛危重的影响 疾病后果。我接受过重症监护和睡眠医学方面的相关临床培训。我已经有了耐心- 通过在ICU中进行几项与睡眠干扰有关的研究，获得了定向研究经验。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) 昼夜夹带干预，以及(3)纵向数据分析。完成这些培训活动将 弥合知识差距，并作为一名独立研究人员建立未来的成功。 导师和环境：我得到了亨利·克拉尔·亚吉博士、玛格丽特·皮萨尼博士和南希·雷德克博士的指导， 一支经验丰富、专注于睡眠医学、重症监护医学、昼夜节律领域的专家团队 测量、ICU精神错乱和以病人为中心的研究。这个团队已经展示了合作的成功， 每个成员都带来了独特的专业知识。我还与顾问Kenneth Wright博士(昼夜生物学 专家)和特伦斯·墨菲博士(分析专家)。我的科室主任(加里·德希尔博士)和科室 主任(纳夫塔利·卡明斯基博士)保证，我将继续至少75%的时间致力于 职业发展活动。我们将从耶鲁-纽黑文医院医疗重症监护室招募研究对象 这是一个大容量的ICU，有足够的病人来使这个项目可行。我们这一部分的翻译 Research Core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 睡眠障碍可能是导致ICU精神错乱的原因之一，建议促进睡眠 用于治疗和预防精神错乱。目前，缺乏关于潜在的 昼夜节律异常对ICU睡眠中断和随之而来的精神错乱的问题有重大贡献。 昼夜节律异常是潜在的可改变的，因此构成了ICU妄想的新的治疗靶点。 该项目将前瞻性地研究ICU患者的详细昼夜节律措施。我们将研究其影响 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，我们将进行试点随机对照试验，以评估 为ICU患者提供日间强光，以促进昼夜节律夹带。

项目成果

Adding Insult to Injury: Sleep Deficiency in Hospitalized Patients.

• DOI: 10.1016/j.ccm.2022.02.009
• 发表时间: 2022-06
• 期刊: CLINICS IN CHEST MEDICINE
• 影响因子: 5.7
• 作者: Mansour, Wissam;Knauert, Melissa
• 通讯作者: Knauert, Melissa