Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients.
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Abstract
RATIONALE: Limitations in methods for the rapid diagnosis of hospital-acquired infections often delay initiation of effective antimicrobial therapy. New diagnostic approaches offer potential clinical and cost-related improvements in the management of these infections. OBJECTIVES: We developed a decision modeling framework to assess the potential cost-effectiveness of a rapid biomarker assay to identify hospital-acquired infection in high-risk patients earlier than standard diagnostic testing. METHODS: The framework includes parameters representing rates of infection, rates of delayed appropriate therapy, and impact of delayed therapy on mortality, along with assumptions about diagnostic test characteristics and their impact on delayed therapy and length of stay. Parameter estimates were based on contemporary, published studies and supplemented with data from a four-site, observational, clinical study. Extensive sensitivity analyses were performed. The base-case analysis assumed 17.6% of ventilated patients and 11.2% of nonventilated patients develop hospital-acquired infection and that 28.7% of patients with hospital-acquired infection experience delays in appropriate antibiotic therapy with standard care. We assumed this percentage decreased by 50% (to 14.4%) among patients with true-positive results and increased by 50% (to 43.1%) among patients with false-negative results using a hypothetical biomarker assay. Cost of testing was set at $110/d. MEASUREMENTS AND MAIN RESULTS: In the base-case analysis, among ventilated patients, daily diagnostic testing starting on admission reduced inpatient mortality from 12.3 to 11.9% and increased mean costs by $1,640 per patient, resulting in an incremental cost-effectiveness ratio of $21,389 per life-year saved. Among nonventilated patients, inpatient mortality decreased from 7.3 to 7.1% and costs increased by $1,381 with diagnostic testing. The resulting incremental cost-effectiveness ratio was $42,325 per life-year saved. Threshold analyses revealed the probabilities of developing hospital-acquired infection in ventilated and nonventilated patients could be as low as 8.4 and 9.8%, respectively, to maintain incremental cost-effectiveness ratios less than $50,000 per life-year saved. CONCLUSIONS: Development and use of serial diagnostic testing that reduces the proportion of patients with delays in appropriate antibiotic therapy for hospital-acquired infections could reduce inpatient mortality. The model presented here offers a cost-effectiveness framework for future test development.
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Tsalik, Ephraim L, Yanhong Li, Lori L Hudson, Vivian H Chu, Tiffany Himmel, Alex T Limkakeng, Jason N Katz, Seth W Glickman, et al. (2016). Potential Cost-effectiveness of Early Identification of Hospital-acquired Infection in Critically Ill Patients. Ann Am Thorac Soc, 13(3). pp. 401–413. 10.1513/AnnalsATS.201504-205OC Retrieved from https://hdl.handle.net/10161/12538.
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Alexander Tan Limkakeng
Dr. Alexander T. Limkakeng, Jr., MD, MHSc, FACEP is a Professor of Emergency Medicine, Vice Chair of Clinical Research, Director of the Acute Care Research Team, and Director of the Resident Research Fellowship for the Department of Emergency Medicine in the Duke University School of Medicine in Durham, North Carolina.
Dr. Limkakeng has served as chair of the American College of Emergency Physicians (ACEP) Research Committee, and been the Course Director of the ACEP Research Forum from 2016-2018, the largest emergency medical research platform in the nation. He is also the Assistant Director of ACEP’s Emergency Medicine Basic Research Skills course. He was elected to the Nominating Committee of the Society of Academic Emergency Medicine.
As a researcher, Dr. Limkakeng has led multiple clinical trials and interdepartmental sponsored projects and is author on over 100 peer-reviewed manuscripts. These include studies in emergency conditions such as COVID-19, traumatic brain injury, hypertension, heart failure, thrombosis, stroke, envenomations, and septic shock. His research has been funded by grants totaling over $5 million dollars. He has lectured internationally on acute coronary syndrome, responsible conduct of research, design of clinical trials, and precision medicine in emergency care. He has led Duke’s involvement in NIH-funded research networks and industry-funded work that led to FDA approval for multiple high-sensitivity cardiac troponin assays. He now serves as Co-PI for the Duke U24 Hub in the NIH Early Phase Pain Investigation Clinical Network (EPPIC-Net) (1U24NS114416) and a co-PI on the Duke U24 Hub award (1U24NS129498) in the NIH Strategies to Innovate Emergency Care Clinical Trials (SIREN) Network.
His personal research interest is finding new ways to diagnose acute coronary syndrome. In particular, he is interested in novel biomarkers and precision medicine approaches to this problem. The common element throughout this work is a focus on time-sensitive health conditions.
Jason Neil Katz
Micah Thomas McClain
Karen Elizabeth Welty-Wolf
Dr. Welty-Wolf studies (1) pathophysiology and treatment of acute lung injury and (2) multiple organ failure and disordered energy metabolism in sepsis. Injury models include hyperoxic lung injury and ARDS with multiple organ failure due to sepsis. In addition to evaluating mechanisms of lung injury in sepsis, current studies are being conducted to evaluate the potential role of monoclinal antibodies to neutrophil adhesion molecules in the prevention of this injury. Other sepsis work includes evaluating mechanisms of oxidative damage to mitochondria. Additional research efforts include evaluating the use of human recombinant manganese superoxide dismutase in preventing hyperoxic lung injury.
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