Biomarkers and Risk Stratification in Pediatric Community-Acquired Pneumonia

儿科社区获得性肺炎的生物标志物和风险分层

• 批准号: 9012197
• 负责人: Todd Adam Florin
• 金额: $ 17.55万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9012197
• 关键词: 18 year old; Accident and Emergency department; Acute; Address; Adult; Award; Bacterial Infections; Benchmarking; Biological Assay; Biological Markers; Caring; Cessation of life; Child; Child Care; Childhood; Clinical; Clinical Data; Clinical Investigator; Clinical Management; Clinical Research; Cohort Studies; Communities; Data; Data Sources; Databases; Decision Aid; Decision Making; Deterioration; Development; Development Plans; Diagnosis; Diagnostic tests; Disease; Disease Progression; Emergency Medicine; Enrollment; Ensure; Environment; Epidemiologic Methods; Funding; Future; Goals; Guidelines; Hospitalization; Image; Immune response; Infection; Infectious Diseases Research; Inpatients; Institution; Instruction; Intensive Care; Judgment; Knowledge; Laboratories; Measurement; Measures; Mechanical ventilation; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Molecular Epidemiology; Morbidity - disease rate; Outcome; Outpatients; Patient risk; Patients; Pediatric Hospitals; Pediatric Research; Physicians; Pneumonia; Polymerase Chain Reaction; Positioning Attribute; Recruitment Activity; Research; Research Infrastructure; Research Methodology; Research Personnel; Research Training; Resources; Risk; Risk Factors; Role; Scientist; Septic Shock; Severities; Severity of illness; Site; Specimen; Statistical Methods; Stratification; Streptococcus pneumoniae; Testing; Time; Training; Translational Research; United States; Variant; White Blood Cell Count procedure; Work; biobank; biomarker development; biomarker discovery; career development; clinical biomarkers; clinical care; clinical decision-making; cohort; disorder risk; evidence base; experience; high risk; improved; infectious disease model; laboratory experience; meetings; multidisciplinary; novel; outcome prediction; pathogen; predict clinical outcome; predictive modeling; procalcitonin; prospective; public health relevance; tool

 DESCRIPTION (provided by applicant): Community-acquired pneumonia (CAP) is the most common serious bacterial infection in children and a leading cause of pediatric hospitalization. Despite its significance, the decision to hospitalize a child with CAP is currently made using clinical factors, imaging and tests that do not accurately or reliably assess disease risk. The result is substantial variation in hospitalization rates and clinical management. Three newer biomarkers - procalcitonin, proadrenomedullin, and pneumococcal bacterial load - have demonstrated potential to improve severity prediction in CAP. Yet, there are currently no evidence-based clinical prediction rules to gauge disease severity or predict clinical outcomes among children with CAP. The extensive variation in care, in addition to the lack of evidence-based decision aids, highlights the critical need for an improved understanding of disease severity and tools to guide management for pediatric CAP. The proposed research will address this important knowledge and practice gap by pursuing the following specific aims: (1) to determine the association between host and pathogen biomarkers and clinical outcomes, including need for hospitalization, in children with CAP; and (2) to develop and internally validate a clinical prediction rule for need for hospitalization of children with CAP. To achieve these aims, the candidate, Todd Florin, MD, MSCE, will leverage an existing study infrastructure developed in conjunction with his mentors during his KL2 award and that has been enrolling children with CAP since July 2013. The robust infrastructure, the primary data source for this K23, includes an active enrollment mechanism in the Cincinnati Children's Hospital Medical Center (CCHMC) ED and the development of a biorepository of specimens from children with CAP. As a pediatric emergency medicine physician, Dr. Florin is uniquely positioned to accomplish the proposed K23 research and training aims. Dr. Florin's long-term goal is to become an expert in clinical and translational research methods to improve the diagnosis and outcomes of pediatric CAP and other common, serious pediatric infections in the acute care setting. In order to expand his research training to include advanced statistical methods in predictive modeling, molecular epidemiology, biomarker discovery, and multicenter pediatric emergency medicine research, Dr. Florin has developed a detailed career development plan consisting of mentorship, didactic coursework, hands-on laboratory experience and completion of the proposed research. He has assembled a multidisciplinary team of experienced mentors with expertise in pediatric pneumonia, infectious diseases research, biomarker discovery, predictive modeling and multicenter emergency medicine research. Dr. Florin will meet regularly with his mentors individually, and quarterly as a full committee, to ensure completion of all research and training benchmarks. The institutional commitment to young researchers at CCHMC, one of the largest pediatric research institutions in the United States, provides an ideal collaborative training environment by providing the strong mentorship, formal instruction, statistical database support, specialized laboratories, and practical experiences necessary to develop into an independent clinical investigator. This proposal will allow Dr. Florin to make significant contributions to pediatric infectious diseases research in the ED as an independent physician-scientist and prepare him for future R01-funded projects focused on use of biomarkers to improve pneumonia diagnosis and management in children.

 描述(申请人提供)：社区获得性肺炎(CAP)是儿童最常见的严重细菌感染，也是儿科住院的主要原因。尽管意义重大，但目前住院治疗CAP儿童的决定是使用临床因素、成像和测试做出的，这些因素不能准确或可靠地评估疾病风险。结果是住院率和临床管理有很大差异。三个较新的生物标志物--降钙素原、肾上腺髓质素原和肺炎球菌细菌负荷--已显示出改善CAP严重程度预测的潜力。然而，目前还没有基于证据的临床预测规则来评估CAP儿童的疾病严重程度或预测临床结果。除了缺乏循证的决策辅助工具外，护理方面的广泛差异也突显了改善对疾病严重性的了解和指导儿科CAP治疗的工具的迫切需要。拟议的研究将通过追求以下具体目标来解决这一重要的知识和实践差距：(1)确定宿主和病原体生物标记物与临床结果之间的联系，包括CAP儿童的住院需求；以及(2)开发和内部验证CAP儿童住院需求的临床预测规则。为了实现这些目标，候选人托德·弗洛林，医学博士，MSCE，将利用在他的KL2奖项期间与他的导师一起开发的现有研究基础设施，该基础设施自2013年7月以来一直在招收儿童参加CAP。强大的基础设施是这份K23的主要数据来源，包括辛辛那提儿童医院医疗中心(CCHMC)ED的积极登记机制，以及开发CAP儿童标本的生物资料库。作为一名儿科急救内科医生，弗洛林博士在实现拟议的K23研究和培训目标方面具有得天独厚的优势。弗洛林博士的长期目标是成为临床和转化性研究方法方面的专家，以改善儿科CAP和其他急性护理环境中常见的严重儿科感染的诊断和预后。为了扩大他的研究培训，将预测建模、分子流行病学、生物标记物发现和多中心儿科急救医学研究中的先进统计方法包括在内，弗洛林博士制定了一项详细的职业发展计划，包括指导、授课课程、动手实验室经验和完成拟议的研究。他组建了一支由经验丰富的导师组成的多学科团队，这些导师在儿科肺炎、传染病研究、生物标记物发现、预测建模和多中心急救医学研究方面具有专业知识。弗洛林博士将定期单独与他的导师会面，并作为一个完整的委员会每季度会面一次，以确保完成所有研究和培训基准。CCHMC是美国最大的儿科研究机构之一，机构对年轻研究人员的承诺提供了一个理想的协作培训环境，提供了强大的指导、正式指导、统计数据库支持、专业实验室和发展为独立临床研究人员所必需的实践经验。这项建议可让弗洛林医生以独立内科科学家的身份，为教育署的儿科传染病研究作出重大贡献，并为未来R01资助的项目作好准备，这些项目的重点是利用生物标记物改善对儿童肺炎的诊断和治疗。