Optimizing the Diagnostic Strategy for Acute Musculoskeletal Infections in Children: Evaluating the Clinical Performance and Comparative Cost of a Noninvasive Diagnostic Technique

优化儿童急性肌肉骨骼感染的诊断策略：评估无创诊断技术的临床表现和比较成本

• 批准号: 10664298
• 负责人: Justin Benjamin Searns
• 金额: $ 18.78万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-03 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664298
• 关键词: Acute; Address; Agreement; Algorithms; Award; Biological Testing; Biopsy; Blood; Blood specimen; Caring; Child; Child Care; Childhood; Clinical; Code; Collection; Colorado; Communicable Diseases; Consumption; Cost Analysis; DNA; Data; Database Management Systems; Databases; Dedications; Diagnostic; Diagnostic Procedure; Diagnostic Trial; Diagnostic tests; Disease; Enrollment; Equilibrium; Frequencies; Future; Goals; Guidelines; Health Information System; Hematogenous; Hospitalization; Hospitals; Infection; Inpatients; Institution; Interventional radiology; Intravenous; Investigation; Joints; Length; Length of Stay; Life; Mentorship; Microbiological Techniques; Microbiology; Modality; Molecular Diagnostic Testing; Morbidity - disease rate; Musculoskeletal; Operative Surgical Procedures; Osteomyelitis; Outcome; Pathogen detection; Patients; Pediatric Hospitals; Performance; Population; Procedures; Prospective Studies; Prospective, cohort study; Publishing; Recommendation; Reference Standards; Research; Research Personnel; Resources; Risk; Sedation procedure; Societies; Source; Specimen; Techniques; Testing; Training; United States; Variant; antimicrobial; bone; career; case finding; cell free DNA; clinical care; comparative; cost; cost comparison; cost estimate; diagnostic strategy; disability; hospital readmission; improved; innovation; interest; liquid biopsy; microbial; microcosting; minimally invasive; multidisciplinary; next generation sequencing; noninvasive diagnosis; novel diagnostics; pathogen; pathogenic bacteria; peripheral blood; prevent; primary outcome; relative cost; sample collection; skills; standard of care; standardized care; targeted treatment

PROJECT SUMMARY/ABSTRACT Pediatric musculoskeletal infections (MSKIs) are burdensome disorders that consume significant hospital re- sources and require prompt antimicrobial treatment to prevent systemic morbidity and life-altering disability. Identifying the causative bacterial culprit for MSKIs improves care by quickly targeting therapy. However, many children suffering from MSKIs never have their bacterial cause identified using existing microbiological tech- niques. Blood cultures are minimally invasive and inexpensive but only find the pathogen in 30-50% of MSKIs. Surgically-collected biopsies of infected musculoskeletal specimens (i.e., “source cultures”) increase diagnostic yield by 30% but require invasive and expensive diagnostic procedures with potential harm from sedation and surgery. Studies are needed to identify the optimal diagnostic strategy for MSKIs (i.e., routine use of invasive procedures versus blood culture alone). The Pediatric Health Information System (PHIS) database contains administrative data from millions of inpatient encounters and could be leveraged to efficiently study the diag- nostic variability for MSKIs at 52 pediatric hospitals in the United States. In addition, new diagnostic modalities have emerged that hold promise for pediatric MSKIs but need further study in these patients. Specifically, next- generation sequencing of microbial cell-free DNA (mcfDNA) from a peripheral blood specimen is a newly de- veloped non-invasive diagnostic test that uses a “liquid biopsy” to detect more than 1000 potential pathogens. Although mcfDNA testing is approved for clinical use, this test has not been validated in children with MSKIs specifically. The lack of evidence for how mcfDNA compares to invasive diagnostic procedures limits its clinical utility in this population. The Infectious Diseases Society of America (IDSA) recently called for new studies to determine whether mcfDNA testing could improve care for pediatric MSKIs. In addition, mcfDNA has an esti- mated cost of more than $2000, and cost analyses are needed to justify its use. This proposal aims to address the critical need for an optimized diagnostic strategy in pediatric MSKIs by (1) describing national variability in diagnostic testing and associated clinical outcomes for acute pediatric MSKIs; (2) determining the clinical performance of non-invasive mcfDNA testing for MSKIs compared to microbiological testing of surgically collected bone and joint specimens; (3) describe the cost of mcfDNA as compared to existing diagnostic options for pediatric MSKIs. This project is the culmination of this candidate’s dedication to improving clinical outcomes for children hospitalized with MSKIs. The objective of this award is for the candidate to develop the skills needed to meet his long-term goal of becoming an independent investigator studying diagnostic innovation for pediatric infections. The candidate will build on his research skillset through expert mentorship, didactic coursework, and experiential training in diagnostic trials and descriptive cost analyses. The candidate has thoughtfully assembled a multidisciplinary mentorship team with extensive expertise in the above aims to help him successfully complete his career training goals and research specific aims.

项目摘要/摘要 儿科肌肉骨骼感染(MSKI)是一种负担沉重的疾病，需要大量的住院治疗。 这是一种疾病来源，需要及时进行抗菌素治疗，以防止系统性疾病和改变生活的残疾。 找出MSKIs的致病细菌罪魁祸首，通过快速靶向治疗改善了护理。然而，许多人 患有MSKI的儿童永远不会使用现有的微生物技术来确定他们的细菌原因- 小甜饼。血液培养是微创和廉价的，但只在30%-50%的MSKI中发现病原体。 通过手术收集的感染肌肉骨骼标本的活组织检查(即“来源培养”)增加了诊断能力。 收益率为30%，但需要侵入性且昂贵的诊断程序，可能会对镇静和 做手术。需要研究来确定MSKI的最佳诊断策略(即常规使用侵入性 程序与血液培养相比)。儿童健康信息系统(PHIS)数据库包含 数以百万计的住院患者的管理数据，并可用于有效地研究诊断- 美国52家儿科医院MSKI的诊断变异性。此外，新的诊断模式 已经出现了对儿科MSKI有希望但需要在这些患者中进行进一步研究的药物。具体地说，接下来- 从外周血标本中提取微生物无细胞DNA(McfDNA)是一种新的方法。 开发的非侵入性诊断测试，使用“液体活组织检查”来检测1000多种潜在病原体。 尽管mcfdna检测已被批准用于临床，但这项检测尚未在患有MSKI的儿童中得到验证。 具体地说。缺乏mcfDNA与侵入性诊断程序相比较的证据限制了其临床应用。 在这一群体中的效用。美国传染病学会(IDSA)最近呼吁进行新的研究 确定mcfDNA检测是否可以改善儿童MSKI的护理。此外，mcfDNA还具有一种 配对成本超过2000美元，需要进行成本分析才能证明其使用的合理性。这项提案旨在解决 儿童MSKI优化诊断战略的迫切需要：(1)描述国家变异性 儿童急性MSKI的诊断试验和相关的临床结果；(2)确定临床 MSKI非侵入性mcfDNA检测与外科微生物学检测的性能比较 收集的骨和关节标本；(3)描述mcfDNA与现有诊断方法相比的成本。 儿科MSKI的选择。这个项目是这位候选人致力于改善临床工作的顶峰 因MSKI住院的儿童的结局。这一奖项的目标是让候选人发展 达到他成为一名研究诊断的独立调查员的长期目标所需的技能 针对儿科感染的创新。候选人将通过专家指导来建立他的研究技能， 教学课程，以及诊断试验和描述性成本分析方面的经验培训。候选人 深思熟虑地组建了一支在上述领域拥有广泛专业知识的多学科指导团队，旨在 帮助他顺利完成职业培训目标和研究的具体目标。