Prognostic modeling of pediatric tracheostomy-associated respiratory tract infections

项目总结： 每年有4000多名儿童接受气管切开术，其中2万多人住院 每年最常见的原因是急性气管造口相关呼吸道感染(Tari)。这些 住院最常见的原因是铜绿假单胞菌感染。努力改善对老年人的护理 接受气管切开术的儿童面临着有限的证据的挑战，这些证据表明患者的因素、特征 铜绿假单胞菌本身和儿童的免疫反应影响复发感染的风险。这项提议将 通过确定和描述频繁发作的预测因素来解决这一关键的知识差距 因塔里住院的儿童再次住院。在这个K23导师职业发展奖中，John博士 莫里森将：1)利用六个中心对因以下原因住院的儿童进行的前瞻性队列研究的现有数据 确定与复发的Tari住院相关的临床因素；2)前瞻性地确定 病原体特异性因素和宿主免疫反应特征与复发频率的关系 Tari住院，以及3)推导出一个新的预后模型，该模型包含了临床和分子因素 确定复发塔里住院的风险增加的患者。实现这些目标将有利于Dr。 莫里森的长期目标是领导旨在改善预后分层干预研究 气管切开术的儿童和其他经常受到呼吸道感染影响的儿童的结局。 申请人致力于改善对慢性呼吸衰竭儿童的护理，并 作为内科科学家的其他医学复杂性。他是约翰斯医院的儿科学助理教授 霍普金斯大学(JHU)约翰霍普金斯大学所有儿童医院(JHACH)医学院寻求 导师职业发展奖，在此期间他将发展高级培训、教育和 在生物标记物信息预后模型和风险方面成为独立资助的研究人员的经验 儿童气管切开术的分层临床试验。这项提案将为莫里森博士提供支持 需要通过1)获得关于预测的开发和应用的知识来推进他的职业生涯 建模，2)开发基于生物样品的翻译研究的专业知识，3)准备 进行前瞻性的多中心研究，验证预后模型并检查治疗策略， 以及4)扩大他对导致复发的个人和系统层面因素的实际理解 气管切开术儿童的入院情况。莫里森博士将得到广泛的资源支持 JHACH和JHU的临床和翻译研究所，并组建了一支强大的 在生物标记物发现、生物标记物信息预后建模和风险分层方面具有专业知识的导师 临床试验。他还将通过JHU布隆伯格公共卫生学院在#年攻读课程 生物统计学、分子流行病学和临床试验指导，以补充他在基础和 临床科学，并获得过渡到独立所需的技能。

PROJECT SUMMARY: Each year over 4,000 children undergo tracheotomy and account for more than 20,000 hospitalizations annually most commonly due to acute tracheostomy-associated respiratory infections (TARI). These hospitalizations are most often due to Pseudomonas aeruginosa infection. Efforts to improve the care of children with tracheostomy are challenged by the limited body of evidence on how patient factors, features of P. aeruginosa itself, and the child's immune response impact the risk of recurrent infection. This proposal will address this critical knowledge gap by identifying and characterizing prognostic factors for frequent rehospitalization in children hospitalized for TARI. In this K23 Mentored Career Development Award, Dr. John Morrison will: 1) leverage existing data from a six-center prospective cohort study of children hospitalized for TARI to identify clinical factors associated with recurrent TARI hospitalization; 2) prospectively determine the association of pathogen-specific factors and features of the host immune response with frequency of recurrent TARI hospitalization, and 3) derive a novel prognostic model incorporating clinical and molecular factors to identify patients at increased risk for recurrent TARI hospitalization. Achieving these aims will facilitate Dr. Morrison's long-term goal of leading prognostically-stratified interventional studies aimed at improving outcomes for children with tracheostomy and others affected by frequent respiratory infections. The applicant has dedicated his career to improving the care for children with chronic respiratory failure and other medical complexity as a physician-scientist. He is an Assistant Professor of Pediatrics with the Johns Hopkins University (JHU) School of Medicine at Johns Hopkins All Children's Hospital (JHACH) who seeks a mentored career development award during which he will develop the advanced training, education, and experience to become an independently funded investigator in biomarker-informed prognostic models and risk- stratified clinical trials in children with tracheostomy. This proposal will provide Dr. Morrison with the support needed to advance his career by 1) acquiring knowledge on the development and application of prognostic modeling, 2) developing expertise in conducting biospecimen-based translational research, 3) preparing to conduct a prospective, multicenter study validating a prognostic model and examining therapeutic strategies, and 4) expanding his practical understanding of individual- and system-level factors contributing to recurrent admissions among children with tracheostomy. Dr. Morrison will be supported by the extensive resources of the Institutes for Clinical and Translational Research at JHACH and JHU and has assembled a strong team of mentors with expertise in biomarker discovery, biomarker-informed prognostic modeling, and risk-stratified clinical trials. He will also pursue coursework through the JHU Bloomberg School of Public Health in biostatistics, molecular epidemiology, and clinical trial conduct to complement his experience in the basic and clinical sciences and acquire the skills necessary to transition to independence.