Prognostic modeling of pediatric tracheostomy-associated respiratory tract infections

项目概要： 每年有4，000多名儿童接受气管切开术，并有20，000多人住院治疗 最常见的是由于急性气管造口相关的呼吸道感染（TARI）。这些 住院治疗最常是由于绿脓杆菌感染。努力改善对残疾人的照顾 气管切开术的儿童受到关于患者因素、 p.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。这项建议会 通过识别和描述常见的预后因素来解决这一关键的知识缺口。 因TARI住院的儿童再次住院。在这个K23指导职业发展奖，约翰博士 莫里森将：1）利用来自一项六中心前瞻性队列研究的现有数据，该研究对因以下原因住院的儿童进行了研究： TARI，以确定与复发性TARI住院相关的临床因素; 2）前瞻性确定 病原体特异性因素和宿主免疫应答特征与复发性 TARI住院，和3）推导出一种新的预后模型，将临床和分子因素， 识别TARI复发住院风险增加的患者。实现这些目标将有助于博士。 莫里森的长期目标是领导旨在改善 气管造口术儿童和其他频繁呼吸道感染儿童的结局。 申请人致力于改善慢性呼吸衰竭儿童的护理， 作为一名医生兼科学家，他是约翰一家的儿科助理教授 霍普金斯大学（JHU）约翰霍普金斯全儿童医院（JHACH）医学院， 指导职业发展奖，在此期间，他将发展先进的培训，教育， 成为生物标志物知情的预后模型和风险的独立资助的研究者的经验- 在气管造口术的儿童中进行分层临床试验。这份提案将为莫里森博士提供支持 需要通过以下方式来推进他的职业生涯：1）获得关于预后的发展和应用的知识 建模，2）发展进行生物技术转化研究的专业知识，3）准备 进行一项前瞻性、多中心研究，验证预后模型并检查治疗策略， 和4）扩大他对个人和系统层面因素的实际理解， 气管切开患儿的入院率。莫里森博士将得到广泛的资源支持， JHACH和JHU的临床和转化研究所，并组建了一支强大的团队， 具有生物标志物发现、生物标志物信息预后建模和风险分层方面专业知识的导师 临床试验他还将通过JHU布隆伯格公共卫生学院进行课程学习， 生物统计学，分子流行病学和临床试验进行，以补充他在基础和 临床科学，并获得必要的技能过渡到独立。

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.