Department of Pediatrics, Division of Infectious Diseases, University of Chicago Medicine, Chicago, IL, USA.
Department of Pediatrics, The University of Chicago, Chicago, IL, USA.
Sci Rep. 2022 May 6;12(1):7429. doi: 10.1038/s41598-022-11576-z.
Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009-2014) and prospective validation (2015-2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension at time of presentation compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn't have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1, 2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden's Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Our prediction model has a very good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduced length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.
发热性中性粒细胞减少症(FN)是接受化疗的儿童中常见的病症。我们在本研究中的目标是开发一种模型,以预测儿科癌症患者 FN 发病时血液感染(BSI)和转入重症监护病房(TIC)的情况。我们对 7 年内因发热和化疗诱导的中性粒细胞减少而住院的儿科和青少年癌症患者进行了一项观察性队列分析。我们排除了接受干细胞移植后发生 FN 并出现发热性非中性粒细胞减少症发作的患者。主要结局是通过 FN 发病后 7 天内的阳性血培养确定 BSI 的发生。次要结局是 FN 发病后 14 天内转入重症监护病房(TIC)。预测变量包括初始 FN 表现时的人口统计学、临床和实验室测量。数据分为独立推导(2009-2014 年)和前瞻性验证(2015-2016 年)队列。使用逻辑回归和随机森林为这两种结果建立预测模型,并与 Hakim 模型进行比较。使用接受者操作特征曲线(ROC)下的面积(AUC)指标评估性能。共确定了 230 名患者中的 505 例 FN 发作(FNEs)。在 106 例(21%)中诊断为 BSI,在 56 例(10.6%)中发生了 TIC。FN 最常见的肿瘤诊断是急性淋巴细胞白血病(ALL),AML 患者的 BSI 发生率最高。与未发生 BSI 的患者相比,发生 BSI 的患者的最高体温更高,BSI 发生率更高,且在发病时低血压的发生率更高。转入重症监护病房(TIC)的 FN 患者的体温和低血压发生率高于未转入 TIC 的 FN 患者。我们比较了 3 种模型:(1)随机森林(2)逻辑回归和(3)Hakim 模型。BSI 预测的曲线下面积分别为模型 1(0.79)、模型 2(0.65)和模型 3(0.64)(P<0.05)。TIC 预测的曲线下面积分别为模型 1(0.88)、模型 2(0.76)和模型 3(0.65)(P<0.05)。随机森林模型在预测 BSI 和 TIC 方面表现出更高的准确性,并在由 Youden 指数确定的最佳截定点处分别显示出 BSI 和 TIC 的阴性预测值(NPV)为 0.91 和 0.97。RF 模型的似然比(LR)(后测概率)具有识别低 BSI 和 TIC 风险(0.24 和 0.12)和高风险患者(3.5 和 6.8)的潜在效用。我们的预测模型在 FN 患者发病时对 BSI 和 TIC 的临床实践具有很好的诊断性能。该模型可用于识别一组低 BSI 风险患者,他们可能受益于提前出院和缩短住院时间,也可以识别出 FN 患者有并发症的高风险,他们可能受益于发病时更强化的治疗。