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External Validation of Six Pediatric Fever and Neutropenia Clinical Decision Rules

Haeusler, Gabrielle M. MBBS1–5; Thursky, Karin A. MD2,5–8; Slavin, Monica A. MD2,5,6,8; Mechinaud, Francoise MD9; Babl, Franz E. MD10–12; Bryant, Penelope PhD11,13; De Abreu Lourenco, Richard PhD14; Phillips, Robert PhD15,16

The Pediatric Infectious Disease Journal: September 5, 2017 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/INF.0000000000001777
Original Studies: PDF Only

Background: Fever and neutropenia (FN) clinical decision rules (CDRs) are recommended to help distinguish children with cancer at high and low risk of severe infection. The aim of this study was to validate existing pediatric FN CDRs, designed to stratify children with cancer at high or low risk of serious infection or medical complication.

Methods: Pediatric CDRs suitable for validation were identified from a literature search. Relevant data were extracted from an existing dataset of 650 retrospective FN episodes in children with cancer. The sensitivity and specificity of each of the CDR were compared with the derivation studies to assess reproducibility.

Results: Six CDRs were identified for validation: two were designed to predict bacteremia and four to predict adverse events. Five CDRs exhibited reproducibility in our cohort. A rule predicting bacteremia had the highest sensitivity (100%; 95% confidence interval (CI) 93-100%) although poor specificity (17%) with only 15% identified as low risk. For adverse events, the highest sensitivity achieved was 84% (95% CI, 75-90%) with specificity of 29% and 27% identified as low risk. A rule intended for application after a 24-hour period of inpatient observation yielded a sensitivity of 80% (95% CI, 73-86) and specificity of 46%, with 44% identified as low-risk.

Conclusion: Five CDRs were reproducible although not all can be recommended for implementation because of either inadequate sensitivity or failure to identify a clinically meaningful number of low-risk patients. The 24-hour rule arguably exhibits the best balance between sensitivity and specificity in our population.

1. The Paediatric Integrated Cancer Service, Parkville, Victoria, Australia, 3052

2. Department of Infectious Diseases, Peter MacCallum Cancer Centre, Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia, 3000

3. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010

4. Department of Infection and Immunity, Monash Children’s Hospital, Department of Paediatrics, Monash University, Clayton, Victoria, Australia, 3168

5. NHMRC National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010

6. Department of Medicine, University of Melbourne, Parkville, Victoria, Australia, 3010

7. NHMRC National Centre for Antimicrobial Stewardship, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia, 3000

8.Victorian Infectious Diseases Service, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia, 3000

9. Children’s Cancer Centre, Royal Children’s Hospital, Parkville, Victoria, Australia, 3052

10. Department of Emergency Medicine, Royal Children's Hospital, Parkville, Victoria, Australia, 3052

11. Murdoch Children's Research Institute, Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia, 3052

12. Department of Paediatrics, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Victoria, Australia, 3010

13. Infectious Diseases Unit, Royal Children's Hospital, Parkville, Victoria, Australia, 3052

14. Centre for Health Economics Research and Evaluation, University of Technology Sydney, Ultimo, New South Wales, Australia, 2007

15. Centre for Reviews and Dissemination, University of York, Heslington, York, UK, YO10 5DD

16. Leeds Children’s Hospital, Leeds General Infirmary, Leeds LS1 3EX, UK

Conflicts of interest and sources of funding: GMH was supported by a National Health and Medical Research Council post-graduate scholarship (GNT1056158). FEB was part funded by a grant from the Royal Children's Hospital Foundation, Melbourne, Australia and an NHMRC Practitioner Fellowship. RP was funded by a Post-Doctoral Research Fellow grant from the NIHR (UK) Grant number PDF-10872. There are no conflicts of interest to declare.

Corresponding author: Dr Gabrielle M. Haeusler, Department of Infectious Diseases, Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, Australia, 3000, P: +61 3 9656 5853 F: +61 3 9656 1185, E: gabrielle.haeusler@petermac.org

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