Haeusler Gabrielle M, Phillips Robert, Slavin Monica A, Babl Franz E, De Abreu Lourenco Richard, Mechinaud Francoise, Thursky Karin A
Department of Infectious Diseases, Peter MacCallum Cancer Centre, Melbourne, Australia.
NHMRC National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
EClinicalMedicine. 2020 Jun 15;23:100394. doi: 10.1016/j.eclinm.2020.100394. eCollection 2020 Jun.
Numerous paediatric febrile neutropenia (FN) clinical decision rules (CDRs) have been derived. Validation studies show reduced performance in external settings. We evaluated the association between variables common across published FN CDRs and bacterial infection and recalibrated existing CDRs using these data.
Prospective data from the Australian-PICNICC study which enrolled 858 FN episodes in children with cancer were used. Variables shown to be significant predictors of infection or adverse outcome in >1 CDR were analysed using multivariable logistic regression. Recalibration included re-evaluation of beta-coefficients (logistic model) or recursive-partition analysis (tree-based models).
Twenty-five unique variables were identified across 17 FN CDRs. Fourteen were included in >1 CDR and 10 were analysed in our dataset. On univariate analysis, location, temperature, hypotension, rigors, severely unwell and decreasing platelets, white cell count, neutrophil count and monocyte count were significantly associated with bacterial infection. On multivariable analysis, decreasing platelets, increasing temperature and the appearance of being clinically unwell remained significantly associated. Five rules were recalibrated. Across all rules, recalibration increased the AUC-ROC and low-risk yield as compared to non-recalibrated data. For the SPOG-adverse event CDR, recalibration also increased sensitivity and specificity and external validation showed reproducibility.
Degree of marrow suppression (low platelets), features of inflammation (temperature) and clinical judgement (severely unwell) have been consistently shown to predict infection in children with FN. Recalibration of existing CDRs is a novel way to improve diagnostic performance of CDRs and maintain relevance over time.
National Health and Medical Research Council Grant (APP1104527).
已得出众多儿童发热性中性粒细胞减少症（FN）临床决策规则（CDR）。验证研究表明，这些规则在外部环境中的表现有所下降。我们评估了已发表的FN CDR中常见变量与细菌感染之间的关联，并利用这些数据对现有CDR进行重新校准。
使用澳大利亚-儿童国际癌症中性粒细胞减少症研究（Australian-PICNICC study）的前瞻性数据，该研究纳入了858例癌症患儿的FN发作。对在>1个CDR中显示为感染或不良结局显著预测因素的变量进行多变量逻辑回归分析。重新校准包括对β系数（逻辑模型）或递归划分分析（基于树的模型）进行重新评估。
在17个FN CDR中识别出25个独特变量。14个变量包含在>1个CDR中，10个变量在我们的数据集中进行了分析。单变量分析显示，部位、体温、低血压、寒战、严重不适以及血小板、白细胞计数、中性粒细胞计数和单核细胞计数下降与细菌感染显著相关。多变量分析显示，血小板减少、体温升高和临床不适表现仍显著相关。对5条规则进行了重新校准。与未重新校准的数据相比，重新校准提高了所有规则的曲线下面积（AUC-ROC）和低风险率。对于SPOG不良事件CDR，重新校准还提高了敏感性和特异性，外部验证显示具有可重复性。
骨髓抑制程度（血小板低）、炎症特征（体温）和临床判断（严重不适）一直被证明可预测FN患儿的感染情况。对现有CDR进行重新校准是提高CDR诊断性能并长期保持相关性的一种新方法。
国家卫生与医学研究委员会拨款（APP1104527）。
