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.

项目总结/文摘