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200万名5岁以下儿童的死亡。在美国（US），尽管总体死亡率较低，但肺炎仍然是儿童住院治疗的最常见指征，相当大比例的儿童患有严重疾病，需要强化心肺干预和延长住院时间。尽管有如此巨大的负担，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巨大的知识差距。其结果是管理上的广泛差异，包括护理决策，诊断测试和抗菌药物的使用，对个人结果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，是一个未满足需求的关键领域。本提案中详细介绍的研究直接响应了这一需求，并包括以下科学目标：1）使用比例优势逻辑回归开发并严格验证临床预测芸香，该预测可预测社区获得性肺炎住院儿童的严重后果风险（CAP）; 2）将微生物学数据的确定并入模型中以评估肺炎病因对预测规则的性能特征的影响; 3）外部验证临床 一个前瞻性观察队列的儿童出现在急诊室与CAP的预测规则。在过去的两年半里，候选人与他的导师和其他研究人员密切合作，对美国三个城市的儿童CAP住院进行前瞻性、基于人群的监测，以确定疾病的发病率和全面的微生物病因。这项研究包括2500多名CAP儿童，将作为拟定预后研究（科学目标1和2）的开发和初步验证的独家数据来源。目标3将招收300名儿童， 在一项前瞻性验证研究中，需要住院治疗CAP的急诊科，以确保所开发模型在新人群中的准确预测性能，并评估其潜在的临床适用性。这种指导职业发展经验的总体目标是候选人成为一名独立的临床研究者，领导一个多学科研究计划，以改善肺炎儿童的护理和结果。为了实现这一目标，候选人将通过预测建模，临床研究，实施科学和领导力培训方面的高级课程和实践技能发展来加强他之前的研究培训。在整个获奖期间，候选人将与一个多学科的导师和导师团队密切合作，包括传染病，生物统计学，医院医学和流行病学专家，以实现他的职业和科学目标。

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.