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

综合生理标志物、生物标志物和临床预测分析，用于早期预警极低出生体重婴儿的败血症和坏死性小肠结肠炎。

• 批准号: 10428595
• 负责人: Brynne Archer Sullivan
• 金额: $ 16.55万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428595
• 关键词: Acute; Algorithms; Antibiotics; Apnea; Award; Big Data; Biological Markers; Bradycardia; Brain; Characteristics; Child; Clinical; Clinical Data; Clinical Markers; Clinical Research; Clinical Trials; Clinical assessments; Collaborations; Communicable Diseases; Data; Data Set; Data Sources; Development Plans; Diagnosis; Disease; Disease Progression; Doctor of Philosophy; Early Diagnosis; Early treatment; Enrollment; Ensure; Environment; Faculty; Fellowship; Funding; Goals; Hand; Heart Abnormalities; Heart Rate; Immune response; Immunologic Markers; Immunology; Infant; Inflammatory; Injury; Laboratories; Life; Measures; Medical; Mentors; Mentorship; Methodology; Mission; Monitor; Morbidity - disease rate; Multi-Institutional Clinical Trial; Multicenter Trials; National Institute of Child Health and Human Development; Necrotizing Enterocolitis; Neonatal Intensive Care Units; Organ; Outcome; Oxygen; Patients; Pattern; Performance; Plasma; Predictive Analytics; Premature Infant; Pulse Oximetry; Randomized Clinical Trials; Records; Recovery; Research; Research Personnel; Resources; Risk; Risk Factors; Risk Marker; Sepsis; Septicemia; Source; Spottings; Step Tests; Survivors; Testing; Time; Time Series Analysis; Training; Training Activity; United States National Institutes of Health; Universities; Validation; Very Low Birth Weight Infant; Virginia; Washington; Work; adverse outcome; automated algorithm; career; career development; chemokine; clinical application; clinical diagnosis; clinical predictors; clinical risk; cytokine; disability; experience; feasibility testing; immune activation; improved; improved outcome; indexing; innovation; large datasets; late onset sepsis; mortality; multidisciplinary; multiorgan damage; novel; prediction algorithm; predictive modeling; professor; randomized trial; response; systemic inflammatory response; tool

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.

项目摘要 候选人：Brynne Sullivan博士是弗吉尼亚大学（UVA）的助理教授，具有以下经验： 研究涉及预测分析在NICU患者中的临床应用。她目前得到了 一个内部指导的职业发展奖，并参加了课程，以获得硕士学位的临床研究。 职业发展计划和目标：拟议的培训计划将使Sullivan博士成为一名临床医生- 具有预测分析专业知识的调查员，以改善危及生命的疾病的诊断和结局 极低出生体重儿（VLBW）的炎症性疾病。奖励期间的培训活动包括 时间序列分析、临床试验方法学和免疫学的研究生课程和辅导。 研究计划：20%的极低出生体重婴儿发生迟发性脓毒症（LOS）和坏死性小肠结肠炎（NEC）， 导致显著的发病率和死亡率。早期诊断和治疗可以开始恢复之前的过程 因此，检测疾病最初迹象的工具可以挽救生命并改善结果 为幸存者。存在LOS和NEC的生理标志物、生物标志物和临床风险标志物，目前作为单独的 数据来源。迫切需要在发病率和死亡率方面与LOS和 NEC将整合数据，开发早期诊断和治疗工具。目标是发展 使用临床、生理标志物和生物标志物数据进行预测分析，并测试整合 这些数据提高了算法性能。具体目标：1）开发并验证脉搏血氧仪 使用心率（HR）和血氧饱和度模式早期检测LOS和NEC的警告评分 （SpO 2），并将性能与使用临床风险的预测模型进行比较 2）确定免疫激活的生物标志物是否告知即将发生LOS和NEC的风险， 3）测试整合的生理标志物、生物标志物和临床监测的可行性。 在一项试点随机试验中进行临床监测，以告知多中心试验的后续步骤，该试验将成为 R 01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，远离疾病或残疾。 导师：主要导师，兰德尔Moorman，医学博士，和二级导师，凯伦费尔柴尔德，医学博士和 William Petri，医学博士，博士，拥有广泛而多样化的专业知识和成功完成 美国国立卫生研究院支持的研究，并指导学员和初级教师成为独立的调查人员。 环境：UVA高级医学分析中心和Petri博士的实验室将提供 为实现本提案的目标所需的知识环境和资源。的特殊 资源和机构的支持，在弗吉尼亚大学和优秀的多学科导师团队将允许 候选人，以实现她的长期目标，成为一个独立的调查员和国家认可的 早产儿致命炎症性疾病的预测分析专家。