Adam J Esbenshade1,2,3, Zhiguo Zhao3,4,5, Catherine Aftandilian6, Raya Saab7, Rachel L Wattier8, Melissa Beauchemin9, Tamara P Miller10, Jennifer J Wilkes10, Michael J Kelly11, Alison Fernbach9, Michael Jeng6, Cindy L Schwartz12, Christopher C Dvorak8, Yu Shyr3,4,5, Karl G M Moons13, Maria-Luisa Sulis9, Debra L Friedman1,2,3. 1. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee. 2. Monroe Carell Jr. Children's Hospital at Vanderbilt, Vanderbilt University Medical Center, Nashville, Tennessee. 3. Vanderbilt-Ingram Cancer Center, Nashville, Tennessee. 4. Department of Biostatistics, Vanderbilt University, Nashville, Tennessee. 5. Center for Quantitative Science, Vanderbilt University School of Medicine, Nashville, Tennessee. 6. Department of Pediatrics, Lucile Packard Children's Hospital, Stanford University, Palo Alto, California. 7. Department of Pediatrics, Children's Cancer Institute, American University of Beirut Medical Center, Beirut, Lebanon. 8. Department of Pediatrics, University of California at San Francisco, San Francisco, California. 9. Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Department of Pediatrics, Columbia University, New York, New York. 10. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 11. Division of Pediatric Hematology/Oncology, The Floating Hospital for Children at Tufts Medical Center, Boston, Massachusetts. 12. Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas. 13. Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.
Abstract
BACKGROUND: Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. METHODS: A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. RESULTS: From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. CONCLUSIONS: The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790.
BACKGROUND: Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness. METHODS: A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables. RESULTS: From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI. CONCLUSIONS: The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017;123:3781-3790.
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