Development and Validation of a Clinical Prediction Rule for Pediatric Pneumonia

描述（由申请人提供）：肺炎是全球儿童的主要杀手，每年造成五分之一的儿童死亡，其中包括每年近200万5岁以下儿童死亡。在美国，尽管总体死亡率较低，但肺炎仍然是儿童中最常见的住院指征，很大一部分患有严重疾病的儿童需要强化心肺干预和长期住院。尽管这是巨大的负担，但在肺炎儿童疾病严重程度的确切决定因素和预期结果方面存在着巨大的知识差距。其结果是管理方面的广泛差异，包括护理地点的决定、诊断检测和抗菌素的使用，对个人结局和社会成本产生下游影响。因此，提高我们对肺炎疾病严重程度的理解，包括准确预测结果的能力，是一个尚未满足需求的关键领域。本提案中详细介绍的研究直接回应了这一需求，并包括以下科学目标：1)开发并严格验证使用比例odds logistic回归预测社区获得性肺炎（CAP）住院儿童严重结局风险的临床预测；2)将微生物学数据的测定纳入模型，评估肺炎病原学对预测规则性能特征的影响；3)外部验证临床

DESCRIPTION (provided by applicant): Pneumonia is the leading killer of children worldwide, responsible for one in five pediatric deaths annually, including nearly 2 million deaths each year among children less than 5 years of age. In the United States (US), despite low overall mortality, pneumonia remains the most common indication for hospitalization among children, with a significant proportion of children experiencing severe disease requiring intensive cardiorespiratory interventions and prolonged hospitalization. Despite this enormous burden, substantial knowledge gaps exist regarding precise determinants of disease severity and expected outcomes for children with pneumonia. The result is wide variation in management-including site of care decisions, diagnostic testing, and use of antimicrobials-with downstream effects on individual outcomes and societal costs. Thus, improving our understanding of pneumonia disease severity, including the ability to accurately predict outcomes, is a critical area of unmet need. The research detailed in this proposal responds directly to this need and includes the following scientific aims: 1) Develop and rigorously validate a clinical prediction rue using proportional odds logistic regression that predicts risk for severe outcomes among children hospitalized with community-acquired pneumonia (CAP); 2) Incorporate the determination of microbiologic data into the model to assess the influence of pneumonia etiology on performance characteristics of the prediction rule; 3) Externally validate the clinical prediction rule among a prospective observational cohort of children presenting to the emergency department with CAP. For the past two and one half years, the candidate has worked closely with his mentor and other investigators to conduct prospective, population-based surveillance for CAP hospitalizations among children in three US cities to determine disease incidence and comprehensive microbiologic etiology. This study includes over 2500 children with CAP and will serve as the exclusive data source for the development and initial validation of the proposed prognostic studies (scientific aims 1 and 2). Aim 3 will enroll 300 children in the emergency department requiring hospital admission for CAP in a prospective validation study to ensure accurate predictive performance of the developed models in new populations and assess their potential clinical applicability. The overarching objective of this mentored career development experience is for the candidate to emerge as an independent clinical investigator leading a multidisciplinary research program to improve care and outcomes for children with pneumonia. To accomplish this goal, the candidate will augment his prior research training with advanced coursework and practical skills development in predictive modeling, clinical research, implementation science, and leadership training. Throughout the award period, the candidate will work closely with a multidisciplinary team of mentors and advisors-including experts in infectious diseases, biostatistics, hospital medicine, and epidemiology-to carry out his stated career and scientific aims. PROJECT NARRATIVE: This proposal seeks to better understand determinants of disease severity for children with pneumonia, the leading killer of children worldwide and the most common reason for childhood hospitalization in the United States. Knowledge of these factors and their often complex interactions will be used to predict risk for severe outcomes among children hospitalized with pneumonia, and could be applied in clinical settings to improve care and outcomes for this population.