Dataset Information

Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study.

ABSTRACT: Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5-10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren't (95% confidence interval, 1.89-7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice.

SUBMITTER: McMullan BJ

PROVIDER: S-EPMC7494114 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study.

McMullan Brendan J BJ Haeusler Gabrielle M GM Hall Lisa L Cooley Louise L Stewardson Andrew J AJ Blyth Christopher C CC Jones Cheryl A CA Konecny Pamela P Babl Franz E FE Mechinaud Françoise F Thursky Karin K

PloS one 20200916 9

Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN bet ...[more]

PMID: 32936822

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Project description:ObjectiveTo examine the association between paternal antidepressant use at conception and offspring preterm birth, malformations, autism spectrum disorder, and intellectual disability.DesignObservational prospective cohort study with regression methods, and negative control comparison.SettingSweden nationwide.Participants170 508 children conceived from 29 July 2005 and born in 2006-07, followed up to 2014 at age 8-9 years. This cohort included 3983 children born to fathers receiving antidepressant treatment during the conception period (that is, from four weeks before conception to four weeks after), a control group of 164 492 children not exposed to paternal antidepressant use, and a negative control comparison group of 2033 children born to fathers who did not use antidepressants during the conception period but began antidepressant treatment later during the pregnancy period (that is, from four weeks after conception to childbirth).Main outcome measureOffspring preterm birth, malformation diagnosed at birth, diagnosis of autism spectrum disorder, and diagnosis of intellectual disability.ResultsPaternal antidepressant use during conception was not associated with preterm birth (adjusted odds ratio 0.91 (95% confidence interval 0.79 to 1.04)) or malformations (1.06 (0.90 to 1.26)) using logistic regression, compared with offspring born to unexposed fathers. No association was seen between antidepressant use during conception and autism (adjusted hazard ratio 1.13 (0.84 to 1.53)) or intellectual disability (0.82 (0.51 to 1.31)) using Cox regression. In children whose fathers initiated antidepressant treatment during pregnancy, results were similar for all outcomes apart from intellectual disability, which had an increased adjusted hazard ratio (1.66 (1.06 to 2.59)). Compared with the 2033 children whose fathers initiated antidepressant treatment during pregnancy, the 3983 children exposed to paternal use of antidepressants at conception had no differences in preterm birth, malformation, and autism, but a reduced risk of intellectual disability (adjusted hazard ratio 0.49 (0.26 to 0.93)).ConclusionPaternal intake of antidepressants during the period around conception is safe with respect to the risk of the four major adverse outcomes in offspring-preterm birth, malformation, autism, or intellectual disability.

Project description:BackgroundDiagnosis of pneumonia is critical in managing patients with febrile neutropenia (FN), however, chest X-ray (CXR) has limited performance in the detection of pneumonia. We aimed to evaluate the performance of a deep learning-based computer-aided detection (CAD) system in pneumonia detection in the CXRs of consecutive FN patients and investigated whether CAD could improve radiologists' diagnostic performance when used as a second reader.MethodsCXRs of patients with FN (a body temperature ≥ 38.3 °C, or a sustained body temperature ≥ 38.0 °C for an hour; absolute neutrophil count < 500/mm3) obtained between January and December 2017 were consecutively included, from a single tertiary referral hospital. Reference standards for the diagnosis of pneumonia were defined by consensus of two thoracic radiologists after reviewing medical records and CXRs. A commercialized, deep learning-based CAD system was retrospectively applied to detect pulmonary infiltrates on CXRs. For comparing performance, five radiologists independently interpreted CXRs initially without the CAD results (radiologist-alone interpretation), followed by the interpretation with CAD. The sensitivities and specificities for detection of pneumonia were compared between radiologist-alone interpretation and interpretation with CAD. The standalone performance of the CAD was also evaluated, using area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. Moreover, sensitivity and specificity of standalone CAD were compared with those of radiologist-alone interpretation.ResultsAmong 525 CXRs from 413 patients (52.3% men; median age 59 years), pneumonia was diagnosed in 128 (24.4%) CXRs. In the interpretation with CAD, average sensitivity of radiologists was significantly improved (75.4% to 79.4%, P = 0.003) while their specificity remained similar (75.4% to 76.8%, P = 0.101), compared to radiologist-alone interpretation. The CAD exhibited AUC, sensitivity, and specificity of 0.895, 88.3%, and 68.3%, respectively. The standalone CAD exhibited higher sensitivity (86.6% vs. 75.2%, P < 0.001) and lower specificity (64.8% vs. 75.4%, P < 0.001) compared to radiologist-alone interpretation.ConclusionsIn patients with FN, the deep learning-based CAD system exhibited radiologist-level performance in detecting pneumonia on CXRs and enhanced radiologists' performance.

Project description:BackgroundRisk models of chemotherapy-induced (CIN) and febrile neutropenia (FN) have to date focused on determinants measured at the start of chemotherapy. We extended this static approach with a dynamic approach of CIN/FN risk modeling at the start of each cycle.DesignWe applied predictive modeling using multivariate logistic regression to identify determinants of CIN/FN episodes and related hospitalizations and chemotherapy disturbances (CIN/FN consequences) in analyses at the patient ('ever' during the whole period of chemotherapy) and cycle-level (during a given chemotherapy cycle). Statistical dependence of cycle data being 'nested' under patients was managed using generalized estimation equations. Predictive performance of each model was evaluated using bootstrapped c concordance statistics.ResultsStatic patient-level risk models of 'ever' experiencing CIN/FN adverse events and consequences during a planned chemotherapy regimen included predictors related to history, risk factors, and prophylaxis initiation and intensity. Dynamic cycle-level risk models of experiencing CIN/FN adverse events and consequences in an upcoming cycle included predictors related to history, risk factors, and prophylaxis initiation and intensity; as well as prophylaxis duration, CIN/FN in prior cycle, and treatment center characteristics.ConclusionsThese 'real-world evidence' models provide clinicians with the ability to anticipate CIN/FN adverse events and their consequences at the start of a chemotherapy line (static models); and, innovatively, to assess risk of CIN/FN adverse events and their consequences at the start of each cycle (dynamic models). This enables individualized patient treatment and is consistent with the EORTC recommendation to re-appraise CIN/FN risk at the start of each cycle. Prophylaxis intensity (under-, correctly-, or over-prophylacted relative to current EORTC guidelines) is a major determinant. Under-prophylaxis is clinically unsafe. Over-prophylaxis of patients administered chemotherapy with intermediate or low myelotoxicity levels may be beneficial, both in patients with and without risk factors, and must be validated in future studies.

Dataset Information

Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study.

Publications

Aminoglycoside use in paediatric febrile neutropenia - Outcomes from a nationwide prospective cohort study.

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