Integrated physiomarker, biomarker and clinical predictive analytics for early warning of sepsis and necrotizing enterocolitis in very low birth weight infants.

项目摘要 候选人：Brynne Sullivan博士是弗吉尼亚大学(UVA)的助理教授，在 预测分析在NICU患者中的临床应用研究。她目前得到的支持是 内部指导职业发展奖，并报名参加课程，以获得临床研究硕士学位。 职业发展计划和目标：拟议的培训计划将使沙利文博士成为一名临床医生- 具有预测分析专业知识的调查员，以改善危及生命的诊断和结果 极低出生体重儿(VLBW)的炎症性疾病获奖期内的培训活动包括 时间序列分析、临床试验方法学和免疫学方面的研究生课程和辅导。 研究计划：晚发性败血症(LOS)和坏死性小肠结肠炎(NEC)发生在20%的极低出生体重婴儿和 导致严重的发病率和死亡率。及早诊断和治疗可以提前开始恢复的进程 发生严重伤害；因此，检测疾病最初迹象的工具可以挽救生命并改善结果。 对于幸存者来说。LOS和NEC的生理标记物、生物标记物和临床风险标记物目前是单独存在的 数据来源。迫切需要使洛杉矶和洛杉矶的发病率和死亡率有实质性的不同 NEC将整合数据，开发用于早期诊断和治疗的工具。我们的目标是发展 使用临床、生理标记物和生物标记物数据进行预测性分析，并检验整合 这些数据提高了算法的性能。具体目标：1)开发和验证脉搏血氧计 应用心率和血氧饱和度模式早期检测LOS和NEC的预警评分 (SpO2)，并使用临床风险将性能与预测模型进行比较 因素；2)确定免疫激活的生物标志物是否提示即将发生的LOS和NEC的风险 生理标记物和临床监测的背景；3)综合生理标记物、生物标记物和 在先导性随机试验中进行临床监测，为下一步的多中心试验提供信息，这将是 R01提案。拟议的研究符合NICHD的使命，即确保所有儿童都有 有机会发挥他们的潜力，过上健康和富有成效的生活，不受疾病或残疾的困扰。 导师：主要导师兰德尔·穆尔曼医学博士和二级导师凯伦·费尔柴尔德医学博士和 威廉·佩里博士，医学博士，拥有广泛而多样的专业知识，并在成功完成 NIH支持的研究，并指导受训人员和初级教员成为独立调查人员。 环境：UVA高级医学分析中心和佩里博士的实验室将提供 实现本提案目标所需的智力环境和资源。不同寻常的 弗吉尼亚大学的资源和机构支持以及出色的多学科指导团队将使 实现她成为独立调查员和国家认可的长期目标的候选人 早产儿危及生命的炎症性疾病的预测分析专家。

PROJECT ABSTRACT Candidate: Dr. Brynne Sullivan is an Assistant Professor at the University of Virginia (UVA) with experience in research involving clinical applications of predictive analytics in NICU patients. She is currently supported by an internal mentored career develop award and enrolled in courses to earn a MSc degree in clinical research. Career development plan and goals: The proposed training plan will establish Dr. Sullivan as a clinician- investigator with expertise in predictive analytics to improve diagnosis and outcomes of life-threatening inflammatory illness in very low birth weight infants (VLBW). Training activities during the award period include graduate-level coursework and tutorial in time series analysis, clinical trial methodology and immunology. Research Plan: Late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) occur in 20% of VLBW infants and cause significant morbidity and mortality. Early diagnosis and treatment can start the course to recovery before serious injury occurs; therefore, tools to detect the first signs of illness could save lives and improve outcomes for survivors. Physiomarkers, biomarkers and clinical risk markers of LOS and NEC exist, currently as separate sources of data. The critical need for making a substantial difference in morbidity and mortality from LOS and NEC is to integrate data to develop tools for earlier diagnosis and treatment. The objective is to develop predictive analytics using clinical, physiomarker and biomarker data and test the hypothesis that integrating these data improves algorithm performance. SPECIFIC AIMS: 1) Develop and validate a Pulse Oximetry Warning Score for early detection of LOS and NEC using patterns in heart rate (HR) and oxygen saturation (SpO2) from a large, multi-center data set and compare performance to predictive models using clinical risk factors; 2) Determine whether biomarkers of immune activation inform risk of imminent LOS and NEC in the context of physiomarker and clinical monitoring; 3) Test feasibility of integrated physiomarker, biomarker and clinical monitoring in a pilot randomized trial to inform next steps of a multi-center trial that will be the focus of an R01 proposal. The proposed research is consistent with the NICHD mission to ensure that all children have the chance to fulfill their potential to live healthy and productive lives free from disease or disability. Mentors: The primary mentor, Randall Moorman, MD, and secondary mentors, Karen Fairchild, MD and William Petri, MD, PhD, have broad and diverse expertise and strong track records in successful completion of NIH-supported studies and in mentoring trainees and junior faculty to become independent investigators. Environment: The UVA Center for Advanced Medical Analytics and Dr. Petri's laboratory will provide the intellectual environment and resources necessary to accomplish the goals of this proposal. The exceptional resources and institutional support at UVA and outstanding multi-disciplinary mentorship team will allow the candidate to achieve her long-term goal of becoming an independent investigator and nationally recognized expert in predictive analytics for life-threatening inflammatory illnesses in premature infants.