title: Predicting microbiologically defined infection in febrile neutropenic episodes in children: global individual participant data multivariable meta-analysis.
abstract: Risk-stratified management of fever with neutropenia (FN), allows intensive management of high-risk cases and early discharge of low-risk cases. No single, internationally validated, prediction model of the risk of adverse outcomes exists for children and young people. An individual patient data (IPD) meta-analysis was undertaken to devise one.
  
  
  
  The 'Predicting Infectious Complications in Children with Cancer' (PICNICC) collaboration was formed by parent representatives, international clinical and methodological experts. Univariable and multivariable analyses, using random effects logistic regression, were undertaken to derive and internally validate a risk-prediction model for outcomes of episodes of FN based on clinical and laboratory data at presentation.
  
  
  
  Data came from 22 different study groups from 15 countries, of 5127 episodes of FN in 3504 patients. There were 1070 episodes in 616 patients from seven studies available for multivariable analysis. Univariable analyses showed associations with microbiologically defined infection (MDI) in many items, including higher temperature, lower white cell counts and acute myeloid leukaemia, but not age. Patients with osteosarcoma/Ewings sarcoma and those with more severe mucositis were associated with a decreased risk of MDI. The predictive model included: malignancy type, temperature, clinically 'severely unwell', haemoglobin, white cell count and absolute monocyte count. It showed moderate discrimination (AUROC 0.723, 95% confidence interval 0.711-0.759) and good calibration (calibration slope 0.95). The model was robust to bootstrap and cross-validation sensitivity analyses.
  
  
  
  This new prediction model for risk of MDI appears accurate. It requires prospective studies assessing implementation to assist clinicians and parents/patients in individualised decision making.
authors.affiliation: Centre for Reviews and Dissemination, University of York, York, UK.|Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Phillips
authors.affiliation: Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.|Program in Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Lillian
authors.initials: L
authors.lastname: Sung
authors.affiliation: Department of Pediatrics, University of Bern, Bern, Switzerland.
authors.forename: Roland A
authors.initials: RA
authors.lastname: Ammann
authors.affiliation: Department of Primary Care and Health Sciences, Keele University, Keele, UK.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Riley
authors.affiliation: Istituto G. Gaslini, Genova, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Castagnola
authors.affiliation: Department of Infectious Diseases and Infection Control, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia.|Department of Paediatric Infectious Diseases and The Paediatric Integrated Cancer Service, Monash Children's Hospital, Clayton, Victoria, Australia.
authors.forename: Gabrielle M
authors.initials: GM
authors.lastname: Haeusler
authors.affiliation: Department of Pediatrics, Division of Hematology/Oncology, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Klaassen
authors.affiliation: Department of Pediatric Oncology, University Of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wim J E
authors.initials: WJ
authors.lastname: Tissing
authors.affiliation: Pediatric Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Lehrnbecher
authors.affiliation: Department of Childrens and Young Peoples Oncology, Royal Marsden Hospital, Sutton, Surrey, London, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Chisholm
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Hakim
authors.affiliation: Centre for Reviews and Dissemination, University of York, York, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Ranasinghe
authors.affiliation: EORTC Data Centre and Hopitaux Universitaires Bordet-Erasme-Institut Jules Bordet, Brussels, Belgium.
authors.forename: Marianne
authors.initials: M
authors.lastname: Paesmans
authors.affiliation: Institute of Child Health and Great Ormond Street Childrens Hospital, London, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Hann
authors.affiliation: Centre for Reviews and Dissemination, University of York, York, UK.
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Stewart
mesh_terms: D002648:Child; D064147:Febrile Neutropenia / Q000382:microbiology* / Q000628:therapy; D006801:Humans; D007239:Infections / Q000097:blood* / Q000382:microbiology* / Q000628:therapy; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors