. "Infections" . . . "Prediction of severe infection in children with chemotherapy-induced febrile neutropenia, development of clinical decision rule" . . "Cancer" . . "Neutrop\u00E9nie f\u00E9brile induite par la chimioth\u00E9rapie -- Enfant -- Dissertation universitaire" . "Cancer -- Chez l'enfant" . . . "Contexte: Le pronostic des neutrop\u00E9nie f\u00E9brile (NF) post-chimioth\u00E9rapie de l\u2019enfant a \u00E9t\u00E9 am\u00E9lior\u00E9 par une antibioth\u00E9rapie \u00E0 large spectre syst\u00E9matique. Cependant des infections s\u00E9v\u00E8res ne surviennent que dans 15-25% des cas. Il a \u00E9t\u00E9 recommand\u00E9 en 2012 de faire \u00E9voluer la prise en charge en tenant compte du risque infectieux en utilisant des r\u00E8gles de d\u00E9cision clinique (RDC). Nous avions montr\u00E9 que les outils publi\u00E9s pour distinguer ce risque \u00E9taient peu performants, non valid\u00E9s ou non applicables sur notre population. Une nouvelle RDC (score) permettant de distinguer les \u00E9pisodes de NF \u00E0 bas risque d\u2019infection s\u00E9v\u00E8re a \u00E9t\u00E9 construite. Cette RDC a \u00E9t\u00E9 valid\u00E9e en interne. Compte tenu des diff\u00E9rences mises en \u00E9vidence dans les populations de tumeurs solides et d\u2019h\u00E9mopathies, il pourrait \u00EAtre pertinent d\u2019utiliser un arbre de d\u00E9cision clinique pour classer le risque infectieux dont la premi\u00E8re division serait le type de cancer et de valider cette nouvelle RDC.L\u2019objectif de ce travail \u00E9tait de calibrer cette RDC sous forme d\u2019arbre et de la valider sur un \u00E9chantillon multicentrique pour distinguer les enfants avec NF \u00E0 bas risque d\u2019infection s\u00E9v\u00E8re. M\u00E9thodes: La premi\u00E8re \u00E9tape a \u00E9t\u00E9 d\u2019\u00E9valuer la m\u00E9thodologie de d\u00E9veloppement des RDC d\u00E9j\u00E0 publi\u00E9es pour identifier d\u2019\u00E9ventuelles limites m\u00E9thodologiques. Ensuite, nous avons d\u00E9crit les diff\u00E9rences entre les h\u00E9mopathies ou avec les tumeurs solides. Puis, la nouvelle RDC a \u00E9t\u00E9 calibr\u00E9e sous forme d\u2019un arbre de d\u00E9cision \u00E0 l\u2019aide du logiciel Sipina. Sa performance a \u00E9t\u00E9 \u00E9valu\u00E9e en termes de sensibilit\u00E9 (Se), sp\u00E9cificit\u00E9 (Sp), et rapport de vraisemblance n\u00E9gatif (RVN).En parall\u00E8le, un protocole de validation multicentrique prospectif a \u00E9t\u00E9 mont\u00E9, avec pour objectif une Se proche de 100% et un RVN inf\u00E9rieur \u00E0 0,1. Il a \u00E9t\u00E9 valid\u00E9 par le CCTIRS et par la CNIL. Il a \u00E9t\u00E9 financ\u00E9 par la Ligue Contre le Cancer (72 000 euros). Trente et un centres ont \u00E9t\u00E9 recrut\u00E9s. La RDC n\u2019a \u00E9t\u00E9 appliqu\u00E9e qu\u2019a posteriori ; la prise en charge de cette population n\u2019a donc pas \u00E9t\u00E9 modifi\u00E9e. La performance de la RDC entre la population de validation et construction a \u00E9t\u00E9 analys\u00E9e en termes de Se, Sp, RVN. L\u2019\u00E9valuation des pratiques de prise en charge des NF post-chimioth\u00E9rapie de l\u2019enfant a \u00E9t\u00E9 faite en parall\u00E8le sous la forme d\u2019une enqu\u00EAte nationale, dans la perspective d\u2019une \u00E9tude d\u2019impact ult\u00E9rieure.R\u00E9sultats: L\u2019\u00E9tude de la m\u00E9thodologie des RDC d\u00E9j\u00E0 publi\u00E9es a montr\u00E9 que les crit\u00E8res de d\u00E9veloppement d\u2019une RDC \u00E9taient respect\u00E9s dans 71% des cas (m\u00E9diane). Une RDC avait atteint le plus haut niveau d\u2019\u00E9vidence, mais sa population de construction \u00E9tait diff\u00E9rente de la n\u00F4tre et cette RDC n\u2019\u00E9tait pas reproductible sur notre population. Il existait 2 \u00E0 3 fois plus d\u2019infection s\u00E9v\u00E8re chez les patients atteints d\u2019une h\u00E9mopathie maligne. Deux arbres de d\u00E9cision ont donc \u00E9t\u00E9 construits pour diff\u00E9rencier le risque d\u2019infection s\u00E9v\u00E8re. Pour les patients avec une tumeur solide il avait des Se de 96%, Sp de 59% et RVN \u00E0 0,07, pour ceux avec une h\u00E9mopathie maligne, il avait des Se de 99%, Sp de 52% et RVN \u00E0 0,03. Les inclusions de la validation multicentrique se sont d\u00E9roul\u00E9es de janvier 2012 \u00E0 mai 2016. 1806 \u00E9pisodes ont \u00E9t\u00E9 inclus (333 infections s\u00E9v\u00E8res, 18,4%). L\u2019application de la RDC a \u00E9t\u00E9 faite a posteriori(en cours). L\u2019enqu\u00EAte nationale men\u00E9e en parall\u00E8le sur la prise en charge faite en pratique dans les centres fran\u00E7ais a montr\u00E9 une grande variabilit\u00E9 de prise en charge notamment dans les d\u00E9finitions de la neutrop\u00E9nie et de la fi\u00E8vre. Un travail doit \u00EAtre initi\u00E9 avec la Soci\u00E9t\u00E9 Fran\u00E7aise des Cancers de l\u2019Enfant pour uniformiser la prise en charge des NF et d\u00E9terminer le type d\u2019all\u00E8gement th\u00E9rapeutique \u00E0 proposer en vue de l\u2019\u00E9tude d\u2019impact, en utilisant cette RDC. Conclusion: Les \u00E9tapes de construction et de validation de cette nouvelle RDC ont \u00E9t\u00E9 r\u00E9alis\u00E9es en respectant les standards m\u00E9thodologiques. Une \u00E9tude d\u2019\u00E9valuation de l\u2019impact de la RDC devra \u00EAtre mise en place pour atteindre le plus haut niveau d\u2019\u00E9vidence." . . "Infection -- Dissertation universitaire" . "R\u00E8gle de d\u00E9cision clinique" . "2016" . . "Text" . . "Purpose: Chemotherapy-induced febrile neutropenia (FN) is known to be a risk for severe infection and death in the absence of prompt and appropriate antibiotic therapy. Immediate hospitalization for rapid institution of empirical broad-spectrum intravenous antibiotic therapy has led to reduce the mortality. However, documented or severe infections occur in only 15-25% of cases. In 2012 paediatric guidelines suggested to adapt the management of FN episodes to the infectious risk. In a previous work, none of the published clinical decision rules (CDRs) to rule out severe infections have been validated and have only rarely been tested in an external set of children. The methodological standards used to derive and validate these CDRs were a real concern. A new CDR was previously derived as a scoring system in Lille to classify the patients at high or low risk of severe infection, with a dataset collected in 2 centers in Lille, in following methodological standards. Differences between solid tumours and blood cancers were observed in children with FN for numbers and types of infections. As a result, we considered relevant to build a decision tree model to predict the low risk for severe infection with a first division that could be the type of cancer. This new decision rule was already validated in an internal set of data, but required an external validation.The aim of this project was to calibrate the CDR as a decision tree and validate its performance a posteriori in an external set of patients, using prospectively collected data from multiple centers.Methods: the methodological standards of available CDRs were first analysed. The new CDR derived on a bicentric dataset was reused to calibrate the CDR as a decision tree, using Sipina software. A prospective multicentric observational protocol funded by 72000\u20AC provided by \u201Cla Ligue Contre le Cancer\u201D was developed for an external validation of the CDR to expect near 100% sensitivity (Se) and a negative likelihood ratio (LR) below 0.1. The ethical regulation was followed. Thirty-one centers were recruited in France (27/30 referent centers for management of children with cancer, and 4 proximity centers fit to manage children with FN). The CDR was not applied to the included patients, and remained confidential. The data were collected on an e-CRF \u201Ccapture system\u201D. The data were captured by an assistant of clinical research and controlled by a physician researcher after the monitoring of the data in all centers. The CDR was a posteriori applied on the dataset. The performance of the CDR between validation and derivation sets of patients was analysed in terms of Se, specificity (Sp) and negative LR.Results: the methodological standards of development of a CDR were not always followed for the development of the published CDR predicting infection for FN in children. Only one CDR followed all criteria and reached the highest level of evidence, but this CDR was built in a very different population from our and was not reproducible. A decision tree model of the CDR was built to distinguish children with FN at low risk of severe infection. For children with solid tumours, the CDR had 96% Se, 59% Sp, and a negative LR at 0.07. For children with blood cancers, the CDR had 99% Se, 52% Sp, and a negative LR at 0.03.For external validation, inclusions started in 2012 until May 2016. Of the 31 centers, 23 included 1806 cases (333 severe infections [18.4%]). The retrospective application of the CDR on all included case in ongoing. A national survey was also conducted as the same time to analyse the real management of children with FN in France in order to determine the type of management that could be proposed for low risk patients when the CDR will be tested in an impact study.Conclusion: the different steps for the construction and validation of the new CDR were conducted following standards. This CDR is in progress to reach the highest level of evidence." . "Th\u00E8ses et \u00E9crits acad\u00E9miques" . . . . . "Pr\u00E9dire l'infection s\u00E9v\u00E8re lors des \u00E9pisodes de neutrop\u00E9nie f\u00E9brile post-chimioth\u00E9rapie de l'enfant, d\u00E9veloppement d'une r\u00E8gle de d\u00E9cision clinique" . . "Neutrop\u00E9nie f\u00E9brile" . "Pr\u00E9dire l'infection s\u00E9v\u00E8re lors des \u00E9pisodes de neutrop\u00E9nie f\u00E9brile post-chimioth\u00E9rapie de l'enfant, d\u00E9veloppement d'une r\u00E8gle de d\u00E9cision clinique" . . "Tumeurs -- Enfant -- Dissertation universitaire" . . . . . "Neutrop\u00E9nie -- Chez l'enfant" .