The influence of chest X-ray results on antibiotic prescription for childhood pneumonia in the emergency department.

The aim of this study is to evaluate the influence of chest X-ray (CXR) results on antibiotic prescription in children suspected of lower respiratory tract infections (RTI) in the emergency department (ED). We performed a secondary analysis of a stepped-wedge, cluster randomized trial of children aged 1 month to 5 years with fever and cough/dyspnoea in 8 EDs in the Netherlands (2016-2018), including a 1-week follow-up. We analysed the observational data of the pre-intervention period, using multivariable logistic regression to evaluate the influence of CXR result on antibiotic prescription. We included 597 children (median age 17 months [IQR 9-30, 61% male). CXR was performed in 109/597 (18%) of children (range across hospitals 9 to 50%); 52/109 (48%) showed focal infiltrates. Children who underwent CXR were more likely to receive antibiotics, also when adjusted for clinical signs and symptoms, hospital and CXR result (OR 7.25 [95% CI 2.48-21.2]). Abnormalities on CXR were not significantly associated with antibiotic prescription.Conclusion: Performance of CXR was independently associated with more antibiotic prescription, regardless of its results. The limited influence of CXR results on antibiotic prescription highlights the inferior role of CXR on treatment decisions for suspected lower RTI in the ED. What is Known: • Chest X-ray (CXR) has a high inter-observer variability and cannot distinguish between bacterial or viral pneumonia. • Current guidelines recommend against routine use of CXR in children with uncomplicated respiratory tract infections (RTIs) in the outpatient setting. What is New: • CXR is still frequently performed in non-complex children suspected of lower RTIs in the emergency department • CXR performance was independently associated with more antibiotic prescriptions, regardless of its results, highlighting the inferior role of chest X-rays in treatment decisions.

Evaluation of a clinical decision rule to guide antibiotic prescription in children with suspected lower respiratory tract infection in The Netherlands: A stepped-wedge cluster randomised trial.

BACKGROUND: Optimising the use of antibiotics is a key component of antibiotic stewardship. Respiratory tract infections (RTIs) are the most common reason for antibiotic prescription in children, even though most of these infections in children under 5 years are viral. This study aims to safely reduce antibiotic prescriptions in children under 5 years with suspected lower RTI at the emergency department (ED), by implementing a clinical decision rule. METHODS AND FINDINGS: In a stepped-wedge cluster randomised trial, we included children aged 1-60 months presenting with fever and cough or dyspnoea to 8 EDs in The Netherlands. The EDs were of varying sizes, from diverse geographic and demographic regions, and of different hospital types (tertiary versus general). In the pre-intervention phase, children received usual care, according to the Dutch and NICE guidelines for febrile children. During the intervention phase, a validated clinical prediction model (Feverkidstool) including clinical characteristics and C-reactive protein (CRP) was implemented as a decision rule guiding antibiotic prescription. The intervention was that antibiotics were withheld in children with a low or intermediate predicted risk of bacterial pneumonia (≤10%, based on Feverkidstool). Co-primary outcomes were antibiotic prescription rate and strategy failure. Strategy failure was defined as secondary antibiotic prescriptions or hospitalisations, persistence of fever or oxygen dependency up to day 7, or complications. Hospitals were randomly allocated to 1 sequence of treatment each, using computer randomisation. The trial could not be blinded. We used multilevel logistic regression to estimate the effect of the intervention, clustered by hospital and adjusted for time period, age, sex, season, ill appearance, and fever duration; predicted risk was included in exploratory analysis. We included 999 children (61% male, median age 17 months [IQR 9 to 30]) between 1 January 2016 and 30 September 2018: 597 during the pre-intervention phase and 402 during the intervention phase. Most children (77%) were referred by a general practitioner, and half of children were hospitalised. Intention-to-treat analyses showed that overall antibiotic prescription was not reduced (30% to 25%, adjusted odds ratio [aOR] 1.07 [95% CI 0.57 to 2.01, p = 0.75]); strategy failure reduced from 23% to 16% (aOR 0.53 [95% CI 0.32 to 0.88, p = 0.01]). Exploratory analyses showed that the intervention influenced risk groups differently (p < 0.01), resulting in a reduction in antibiotic prescriptions in low/intermediate-risk children (17% to 6%; aOR 0.31 [95% CI 0.12 to 0.81, p = 0.02]) and a non-significant increase in the high-risk group (47% to 59%; aOR 2.28 [95% CI 0.84 to 6.17, p = 0.09]). Two complications occurred during the trial: 1 admission to the intensive care unit during follow-up and 1 pleural empyema at day 10 (both unrelated to the study intervention). Main limitations of the study were missing CRP values in the pre-intervention phase and a prolonged baseline period due to logistical issues, potentially affecting the power of our study. CONCLUSIONS: In this multicentre ED study, we observed that a clinical decision rule for childhood pneumonia did not reduce overall antibiotic prescription, but that it was non-inferior to usual care. Exploratory analyses showed fewer strategy failures and that fewer antibiotics were prescribed in low/intermediate-risk children, suggesting improved targeting of antibiotics by the decision rule. TRIAL REGISTRATION: Netherlands Trial Register NTR5326.

Validation of the Feverkidstool and procalcitonin for detecting serious bacterial infections in febrile children.

BackgroundTo validate the Feverkidstool, a prediction model consisting of clinical signs and symptoms and C-reactive protein (CRP) to identify serious bacterial infections (SBIs) in febrile children, and to determine the incremental diagnostic value of procalcitonin.MethodsThis prospective observational study that was carried out at two Dutch emergency departments included children with fever, aged 1 month to 16 years. The prediction models were developed with polytomous logistic regression differentiating "pneumonia" and "other SBIs" from "non-SBIs" using standardized, routinely collected data on clinical signs and symptoms, CRP, and procalcitonin.ResultsA total of 1,085 children were included with a median age of 1.6 years (interquartile range 0.8-3.4); 73 children (7%) had pneumonia and 98 children (9%) had other SBIs. The Feverkidstool showed good discriminative ability in this new population. After adding procalcitonin to the Feverkidstool, c-statistic for "pneumonia" increased from 0.85 (95% confidence interval (CI) 0.76-0.94) to 0.86 (0.77-0.94) and for "other SBI" from 0.81 (0.73-0.90) to 0.83 (0.75- 0.91). A model with clinical features and procalcitonin performed similar to the Feverkidstool.ConclusionThis study confirms the external validity of the Feverkidstool, with CRP and procalcitonin being equally valuable for predicting SBI in our population of febrile children. Our findings do not support routine dual use of CRP and procalcitonin.

Practice variation across five European paediatric emergency departments: a prospective observational study.

OBJECTIVES: To compare paediatric healthcare practice variation among five European emergency departments (EDs) by analysing variability in decisions about diagnostic testing, treatment and admission. DESIGN AND POPULATION: Consecutive paediatric visits in five European EDs in four countries (Austria, Netherlands, Portugal, UK) were prospectively collected during a study period of 9-36 months (2012-2015). PRIMARY OUTCOME MEASURES: Practice variation was studied for the following management measures: lab testing, imaging, administration of intravenous medication and patient disposition after assessment at the ED. ANALYSIS: Multivariable logistic regression was used to adjust for general patient characteristics and markers of disease severity. To assess whether ED was significantly associated with management, the goodness-of-fit of regression models based on all variables with and without ED as explanatory variable was compared. Management measures were analysed across different categories of presenting complaints. RESULTS: Data from 111 922 children were included, with a median age of 4 years (IQR 1.7-9.4). There were large differences in frequencies of Manchester Triage System (MTS) urgency and selected MTS presentational flow charts. ED was a significant covariate for management measures. The variability in management among EDs was fairly consistent across different presenting complaints after adjustment for confounders. Adjusted OR (aOR) for laboratory testing were consistently higher in one hospital while aOR for imaging were consistently higher in another hospital. Iv administration of medication and fluids and admission was significantly more likely in two other hospitals, compared with others, for most presenting complaints. CONCLUSIONS: Distinctive hospital-specific patterns in variability of management could be observed in these five paediatric EDs, which were consistent across different groups of clinical presentations. This could indicate fundamental differences in paediatric healthcare practice, influenced by differences in factors such as organisation of primary care, diagnostic facilities and available beds, professional culture and patient expectations.

Shortness of breath in children at the emergency department: Variability in management in Europe.

OBJECTIVE: Our aim was to describe variability in resource use and hospitalization in children presenting with shortness of breath to different European Emergency Departments (EDs) and to explore possible explanations for variability. DESIGN: The TrIAGE project, a prospective observational study based on electronic health record data. PATIENTS AND SETTING: Consecutive paediatric emergency department visits for shortness of breath in five European hospitals in four countries (Austria, Netherlands, Portugal, United Kingdom) during a study period of 9-36 months (2012-2014). MAIN OUTCOME MEASURES: We assessed diversity between EDs regarding resource use (diagnostic tests, therapy) and hospital admission using multivariable logistic regression analyses adjusting for potential confounding variables. RESULTS: In total, 13,552 children were included. Of those, 7,379 were categorized as immediate/very urgent, ranging from 13-80% in the participating hospitals. Laboratory tests and X-rays were performed in 8-33% of the cases and 21-61% was treated with inhalation medication. Admission rates varied between 8-47% and PICU admission rates varied between 0.1-9%. Patient characteristics and markers of disease severity (age, sex, comorbidity, urgency, vital signs) could explain part of the observed variability in resource use and hospitalization. However, after adjusting for these characteristics, we still observed substantial variability between settings. CONCLUSION: European EDs differ substantially regarding the resource use and hospitalization in children with shortness of breath, even when adjusting for patient characteristics. Possible explanations for this variability might be unmeasured patient characteristics such as underlying disease, differences in guideline use and adherence or different local practice patterns.

Improving the prioritization of children at the emergency department: Updating the Manchester Triage System using vital signs.

BACKGROUND: Vital signs are used in emergency care settings in the first assessment of children to identify those that need immediate attention. We aimed to develop and validate vital sign based Manchester Triage System (MTS) discriminators to improve triage of children at the emergency department. METHODS AND FINDINGS: The TrIAGE project is a prospective observational study based on electronic health record data from five European EDs (Netherlands (n = 2), United Kingdom, Austria, and Portugal). In the current study, we included 117,438 consecutive children <16 years presenting to the ED during the study period (2012-2015). We derived new discriminators based on heart rate, respiratory rate, and/or capillary refill time for specific subgroups of MTS flowcharts. Moreover, we determined the optimal cut-off value for each vital sign. The main outcome measure was a previously developed 3-category reference standard (high, intermediate, low urgency) for the required urgency of care, based on mortality at the ED, immediate lifesaving interventions, disposition and resource use. We determined six new discriminators for children <1 year and ≥1 year: "Very abnormal respiratory rate", "Abnormal heart rate", and "Abnormal respiratory rate", with optimal cut-offs, and specific subgroups of flowcharts. Application of the modified MTS reclassified 744 patients (2.5%). Sensitivity increased from 0.66 (95%CI 0.60-0.72) to 0.71 (0.66-0.75) for high urgency patients and from 0.67 (0.54-0.76) to 0.70 (0.58-0.80) for high and intermediate urgency patients. Specificity decreased from 0.90 (0.86-0.93) to 0.89 (0.85-0.92) for high and 0.66 (0.52-0.78) to 0.63 (0.50-0.75) for high and intermediate urgency patients. These differences were statistically significant. Overall performance improved (R2 0.199 versus 0.204). CONCLUSIONS: Six new discriminators based on vital signs lead to a small but relevant increase in performance and should be implemented in the MTS.

A clinical prediction model to identify children at risk for revisits with serious illness to the emergency department: A prospective multicentre observational study.

BACKGROUND: To develop a clinical prediction model to identify children at risk for revisits with serious illness to the emergency department. METHODS AND FINDINGS: A secondary analysis of a prospective multicentre observational study in five European EDs (the TRIAGE study), including consecutive children aged <16 years who were discharged following their initial ED visit ('index' visit), in 2012-2015. Standardised data on patient characteristics, Manchester Triage System urgency classification, vital signs, clinical interventions and procedures were collected. The outcome measure was serious illness defined as hospital admission or PICU admission or death in ED after an unplanned revisit within 7 days of the index visit. Prediction models were developed using multivariable logistic regression using characteristics of the index visit to predict the likelihood of a revisit with a serious illness. The clinical model included day and time of presentation, season, age, gender, presenting problem, triage urgency, and vital signs. An extended model added laboratory investigations, imaging, and intravenous medications. Cross validation between the five sites was performed, and discrimination and calibration were assessed using random effects models. A digital calculator was constructed for clinical implementation. 7,891 children out of 98,561 children had a revisit to the ED (8.0%), of whom 1,026 children (1.0%) returned to the ED with a serious illness. Rates of revisits with serious illness varied between the hospitals (range 0.7-2.2%). The clinical model had a summary Area under the operating curve (AUC) of 0.70 (95% CI 0.65-0.74) and summary calibration slope of 0.83 (95% CI 0.67-0.99). 4,433 children (5%) had a risk of > = 3%, which was useful for ruling in a revisit with serious illness, with positive likelihood ratio 4.41 (95% CI 3.87-5.01) and specificity 0.96 (95% CI 0.95-0.96). 37,546 (39%) had a risk <0.5%, which was useful for ruling out a revisit with serious illness (negative likelihood ratio 0.30 (95% CI 0.25-0.35), sensitivity 0.88 (95% CI 0.86-0.90)). The extended model had an improved summary AUC of 0.71 (95% CI 0.68-0.75) and summary calibration slope of 0.84 (95% CI 0.71-0.97). As study limitations, variables on ethnicity and social deprivation could not be included, and only return visits to the original hospital and not to those of surrounding hospitals were recorded. CONCLUSION: We developed a prediction model and a digital calculator which can aid physicians identifying those children at highest and lowest risks for developing a serious illness after initial discharge from the ED, allowing for more targeted safety netting advice and follow-up.

The Role of the Respiratory Microbiome and Viral Presence in Lower Respiratory Tract Infection Severity in the First Five Years of Life.

Lower respiratory tract infections (LRTIs) in children are common and, although often mild, a major cause of mortality and hospitalization. Recently, the respiratory microbiome has been associated with both susceptibility and severity of LRTI. In this current study, we combined respiratory microbiome, viral, and clinical data to find associations with the severity of LRTI. Nasopharyngeal aspirates of children aged one month to five years included in the STRAP study (Study to Reduce Antibiotic prescription in childhood Pneumonia), who presented at the emergency department (ED) with fever and cough or dyspnea, were sequenced with nanopore 16S-rRNA gene sequencing and subsequently analyzed with hierarchical clustering to identify respiratory microbiome profiles. Samples were also tested using a panel of 15 respiratory viruses and Mycoplasma pneumoniae, which were analyzed in two groups, according to their reported virulence. The primary outcome was hospitalization, as measure of disease severity. Nasopharyngeal samples were isolated from a total of 167 children. After quality filtering, microbiome results were available for 54 children and virology panels for 158 children. Six distinct genus-dominant microbiome profiles were identified, with Haemophilus-, Moraxella-, and Streptococcus-dominant profiles being the most prevalent. However, these profiles were not found to be significantly associated with hospitalization. At least one virus was detected in 139 (88%) children, of whom 32.4% had co-infections with multiple viruses. Viral co-infections were common for adenovirus, bocavirus, and enterovirus, and uncommon for human metapneumovirus (hMPV) and influenza A virus. The detection of enteroviruses was negatively associated with hospitalization. Virulence groups were not significantly associated with hospitalization. Our data underlines high detection rates and co-infection of viruses in children with respiratory symptoms and confirms the predominant presence of Haemophilus-, Streptococcus-, and Moraxella-dominant profiles in a symptomatic pediatric population at the ED. However, we could not assess significant associations between microbiome profiles and disease severity measures.

A Novel Framework for Phenotyping Children With Suspected or Confirmed Infection for Future Biomarker Studies.

Background: The limited diagnostic accuracy of biomarkers in children at risk of a serious bacterial infection (SBI) might be due to the imperfect reference standard of SBI. We aimed to evaluate the diagnostic performance of a new classification algorithm for biomarker discovery in children at risk of SBI. Methods: We used data from five previously published, prospective observational biomarker discovery studies, which included patients aged 0- <16 years: the Alder Hey emergency department (n = 1,120), Alder Hey pediatric intensive care unit (n = 355), Erasmus emergency department (n = 1,993), Maasstad emergency department (n = 714) and St. Mary's hospital (n = 200) cohorts. Biomarkers including procalcitonin (PCT) (4 cohorts), neutrophil gelatinase-associated lipocalin-2 (NGAL) (3 cohorts) and resistin (2 cohorts) were compared for their ability to classify patients according to current standards (dichotomous classification of SBI vs. non-SBI), vs. a proposed PERFORM classification algorithm that assign patients to one of eleven categories. These categories were based on clinical phenotype, test outcomes and C-reactive protein level and accounted for the uncertainty of final diagnosis in many febrile children. The success of the biomarkers was measured by the Area under the receiver operating Curves (AUCs) when they were used individually or in combination. Results: Using the new PERFORM classification system, patients with clinically confident bacterial diagnosis ("definite bacterial" category) had significantly higher levels of PCT, NGAL and resistin compared with those with a clinically confident viral diagnosis ("definite viral" category). Patients with diagnostic uncertainty had biomarker concentrations that varied across the spectrum. AUCs were higher for classification of "definite bacterial" vs. "definite viral" following the PERFORM algorithm than using the "SBI" vs. "non-SBI" classification; summary AUC for PCT was 0.77 (95% CI 0.72-0.82) vs. 0.70 (95% CI 0.65-0.75); for NGAL this was 0.80 (95% CI 0.69-0.91) vs. 0.70 (95% CI 0.58-0.81); for resistin this was 0.68 (95% CI 0.61-0.75) vs. 0.64 (0.58-0.69) The three biomarkers combined had summary AUC of 0.83 (0.77-0.89) for "definite bacterial" vs. "definite viral" infections and 0.71 (0.67-0.74) for "SBI" vs. "non-SBI." Conclusion: Biomarkers of bacterial infection were strongly associated with the diagnostic categories using the PERFORM classification system in five independent cohorts. Our proposed algorithm provides a novel framework for phenotyping children with suspected or confirmed infection for future biomarker studies.

Management of children visiting the emergency department during out-of-office hours: an observational study.

BACKGROUND: The aim was to study the characteristics and management of children visiting the emergency department (ED) during out-of-office hours. METHODS: We analysed electronic health record data from 119 204 children visiting one of five EDs in four European countries. Patient characteristics and management (diagnostic tests, treatment, hospital admission and paediatric intensive care unit admission) were compared between children visiting during office hours and evening shifts, night shifts and weekend day shifts. Analyses were corrected for age, gender, Manchester Triage System urgency, abnormal vital signs, presenting problems and hospital. RESULTS: Patients presenting at night were younger (median (IQR) age: 3.7 (1.4-8.2) years vs 4.8 (1.8-9.9)), more often classified as high urgent (16.3% vs 9.9%) and more often had ≥2 abnormal vital signs (22.8% vs 18.1%) compared with office hours. After correcting for disease severity, laboratory and radiological tests were less likely to be requested (adjusted OR (aOR): 0.82, 95% CI 0.78-0.86 and aOR: 0.64, 95% CI 0.60-0.67, respectively); treatment was more likely to be undertaken (aOR: 1.56, 95% CI 1.49-1.63) and patients were more likely to be admitted to the hospital (aOR: 1.32, 95% CI 1.24-1.41) at night. Patterns in management during out-of-office hours were comparable between the different hospitals, with variability remaining. CONCLUSIONS: Children visiting during the night are relatively more seriously ill, highlighting the need to keep improving emergency care on a 24-hour-a-day basis. Further research is needed to explain the differences in management during the night and how these differences affect patient outcomes.

Sex-specific differences in children attending the emergency department: prospective observational study.

OBJECTIVE: To assess the role of sex in the presentation and management of children attending the emergency department (ED). DESIGN: The TrIAGE project (TRiage Improvements Across General Emergency departments), a prospective observational study based on curated electronic health record data. SETTING: Five diverse European hospitals in four countries (Austria, The Netherlands, Portugal, UK). PARTICIPANTS: All consecutive paediatric ED visits of children under the age of 16 during the study period (8-36 months between 2012 and 2015). MAIN OUTCOME MEASURES: The association between sex (male of female) and diagnostic tests and disease management in general paediatric ED visits and in subgroups presenting with trauma or musculoskeletal, gastrointestinal and respiratory problems and fever. Results from the different hospitals were pooled in a random effects meta-analysis. RESULTS: 116 172 ED visits were included of which 63 042 (54%) by boys and 53 715 (46%) by girls. Boys accounted for the majority of ED visits in childhood, and girls in adolescence. After adjusting for age, triage urgency and clinical presentation, girls had more laboratory tests compared with boys (pooled OR 1.10, 95% CI 1.05 to 1.15). Additionally, girls had more laboratory tests in ED visits for respiratory problems (pooled OR 1.15, 95% CI 1.04 to 1.26) and more imaging in visits for trauma or musculoskeletal problems (pooled OR 1.10, 95% CI 1.01 to 1.20) and respiratory conditions (pooled OR 1.14, 95% CI 1.05 to 1.24). Girls with respiratory problems were less often treated with inhalation medication (pooled OR 0.76, 95% CI 0.70 to 0.83). There was no difference in hospital admission between the sexes (pooled OR 0.99, 95% CI 0.95 to 1.04). CONCLUSION: In childhood, boys represent the majority of ED visits and they receive more inhalation medication. Unexpectedly, girls receive more diagnostic tests compared with boys. Further research is needed to investigate whether this is due to pathophysiological differences and differences in disease course, whether girls present signs and symptoms differently, or whether sociocultural factors are responsible.

Development and validation of a Paediatric Early Warning Score for use in the emergency department: a multicentre study.

BACKGROUND: Paediatric Early Warning Scores (PEWSs) are being used increasingly in hospital wards to identify children at risk of clinical deterioration, but few scores exist that were designed for use in emergency care settings. To improve the prioritisation of children in the emergency department (ED), we developed and validated an ED-PEWS. METHODS: The TrIAGE project is a prospective European observational study based on electronic health record data collected between Jan 1, 2012, and Nov 1, 2015, from five diverse EDs in four European countries (Netherlands, the UK, Austria, and Portugal). This study included data from all consecutive ED visits of children under age 16 years. The main outcome measure was a three-category reference standard (high, intermediate, low urgency) that was developed as part of the TrIAGE project as a proxy for true patient urgency. The ED-PEWS was developed based on an ordinal logistic regression model, with cross-validation by setting. After completing the study, we fully externally validated the ED-PEWS in an independent cohort of febrile children from a different ED (Greece). FINDINGS: Of 119 209 children, 2007 (1·7%) were of high urgency and 29 127 (24·4%) of intermediate urgency, according to our reference standard. We developed an ED-PEWS consisting of age and the predictors heart rate, respiratory rate, oxygen saturation, consciousness, capillary refill time, and work of breathing. The ED-PEWS showed a cross-validated c-statistic of 0·86 (95% prediction interval 0·82-0·90) for high-urgency patients and 0·67 (0·61-0·73) for high-urgency or intermediate-urgency patients. A cutoff of score of at least 15 was useful for identifying high-urgency patients with a specificity of 0·90 (95% CI 0·87-0·92) while a cutoff score of less than 6 was useful for identifying low-urgency patients with a sensitivity of 0·83 (0·81-0·85). INTERPRETATION: The proposed ED-PEWS can assist in identifying high-urgency and low-urgency patients in the ED, and improves prioritisation compared with existing PEWSs. FUNDING: Stichting de Drie Lichten, Stichting Sophia Kinderziekenhuis Fonds, and the European Union's Horizon 2020 research and innovation programme.

Clinical prediction models for young febrile infants at the emergency department: an international validation study.

OBJECTIVE: To assess the diagnostic value of existing clinical prediction models (CPM; ie, statistically derived) in febrile young infants at risk for serious bacterial infections. METHODS: A systematic literature review identified eight CPMs for predicting serious bacterial infections in febrile children. We validated these CPMs on four validation cohorts of febrile children in Spain (age <3 months), France (age <3 months) and two cohorts in the Netherlands (age 1-3 months and >3-12 months). We evaluated the performance of the CPMs by sensitivity/specificity, area under the receiver operating characteristic curve (AUC) and calibration studies. RESULTS: The original cohorts in which the prediction rules were developed (derivation cohorts) ranged from 381 to 15 781 children, with a prevalence of serious bacterial infections varying from 0.8% to 27% and spanned an age range of 0-16 years. All CPMs originally performed moderately to very well (AUC 0.60-0.93). The four validation cohorts included 159-2204 febrile children, with a median age range of 1.8 (1.2-2.4) months for the three cohorts <3 months and 8.4 (6.0-9.6) months for the cohort >3-12 months of age. The prevalence of serious bacterial infections varied between 15.1% and 17.2% in the three cohorts <3 months and was 9.8% for the cohort >3-12 months of age. Although discriminative values varied greatly, best performance was observed for four CPMs including clinical signs and symptoms, urine dipstick analyses and laboratory markers with AUC ranging from 0.68 to 0.94 in the three cohorts <3 months (ranges sensitivity: 0.48-0.94 and specificity: 0.71-0.97). For the >3-12 months' cohort AUC ranges from 0.80 to 0.89 (ranges sensitivity: 0.70-0.82 and specificity: 0.78-0.90). In general, the specificities exceeded sensitivities in our cohorts, in contrast to derivation cohorts with high sensitivities, although this effect was stronger in infants <3 months than in infants >3-12 months. CONCLUSION: We identified four CPMs, including clinical signs and symptoms, urine dipstick analysis and laboratory markers, which can aid clinicians in identifying serious bacterial infections. We suggest clinicians should use CPMs as an adjunctive clinical tool when assessing the risk of serious bacterial infections in febrile young infants.

Validity of the Manchester Triage System in emergency care: A prospective observational study.

OBJECTIVES: To determine the validity of the Manchester Triage System (MTS) in emergency care for the general population of patients attending the emergency department, for children and elderly, and for commonly used MTS flowcharts and discriminators across three different emergency care settings. METHODS: This was a prospective observational study in three European emergency departments. All consecutive patients attending the emergency department during a 1-year study period (2010-2012) were included. Validity of the MTS was assessed by comparing MTS urgency as determined by triage nurses with patient urgency according to a predefined 3-category reference standard as proxy for true patient urgency. RESULTS: 288,663 patients were included in the analysis. Sensitivity of the MTS in the three hospitals ranged from 0.47 (95%CI 0.44-0.49) to 0.87 (95%CI 0.85-0.90), and specificity from 0.84 (95%CI 0.84-0.84) to 0.94 (95%CI 0.94-0.94) for the triage of adult patients. In children, sensitivity ranged from 0.65 (95%CI 0.61-0.70) to 0.83 (95%CI 0.79-0.87), and specificity from 0.83 (95%CI 0.82-0.83) to 0.89 (95%CI 0.88-0.90). The diagnostic odds ratio ranged from 13.5 (95%CI 12.1-15.0) to 35.3 (95%CI 28.4-43.9) in adults and from 9.8 (95%CI 6.7-14.5) to 23.8 (95%CI 17.7-32.0) in children, and was lowest in the youngest patients in 2 out of 3 settings and in the oldest patients in all settings. Performance varied considerably between the different emergency departments. CONCLUSIONS: Validity of the MTS in emergency care is moderate to good, with lowest performance in the young and elderly patients. Future studies on the validity of triage systems should be restricted to large, multicenter studies to define modifications and improve generalizability of the findings.

Neutrophil CD64 expression is not a useful biomarker for detecting serious bacterial infections in febrile children at the emergency department.

BACKGROUND: CD64 is expressed on the surface membrane of neutrophils (nCD64) in the presence of bacterial infection. Although initial studies in intensive care settings have been promising, only two small, methodologically flawed studies have been performed in feverish children presenting to the emergency department (ED), both of which were showing a moderate diagnostic value of nCD64 to detect a serious bacterial infection (SBI). This study aimed to determine the diagnostic value of nCD64 in children presenting with fever to the ED for detecting SBI. METHODS: In this prospective observational multi-centre study previously healthy children aged 1 month-16 years with fever, presenting to the ED of two hospitals in the Netherlands in 2011-2012 were included. Standardised information on clinical features were collected and nCD64 and CRP were measured routinely. Multivariable logistic regression was used to determine the discriminative ability to detect SBI (ROC-area) of nCD64 compared with CRP. Diagnostic performance measures including sensitivity, specificity and likelihood ratios were calculated. RESULTS: In 392 children (45%) with both CRP and nCD64 determined, 52 children (13%) had an SBI. The AUC of the ROC curve for CD64 was 0.62 (95% CI = 0.54-0.70) and 0.75 (95% CI = 0.67-0.83) for CRP. Neither duration of fever nor deviated vital signs influenced the diagnostic performance of nCD64. CONCLUSION: NCD64 expression has poor discriminative value to detect children with an SBI in a general population of febrile children at the ED. It has no superior value compared to CRP in this setting, neither in total nor in sub-populations.

C-reactive protein, procalcitonin and the lab-score for detecting serious bacterial infections in febrile children at the emergency department: a prospective observational study.

BACKGROUND: C-reactive protein (CRP) and procalcitonin (PCT) are useful diagnostic tools to estimate the risk of serious bacterial infection (SBI) in febrile children at the emergency department (ED). The Lab-score combines these 2 biomarkers with urinalysis in an easy to use validated model. Kinetics of inflammatory markers suggests a differentiating role of duration of disease. AIM: : Appraisal of the diagnostic role of CRP and PCT in febrile children at risk of SBI, determining the differentiating value of duration of fever, and validating and updating the Lab-score. METHODS: In this prospective observational study previously healthy children with fever, 1 month to 16 years of age, attending the EDs of a university hospital and a teaching hospital (Rotterdam, the Netherlands) between 2009 and 2012 were included. Standardized information on clinical signs and symptoms, CRP, PCT and urinalysis were collected prospectively. Logistic multivariable regression analysis was used to assess diagnostic performance. The original Lab-score included CRP, PCT and urinalysis and the total score ranged 0-9 points. RESULTS: One thousand eighty-four children were included, median age was 1.6 years (interquartile range: 0.8-3.5), 170 children (16%) had SBI. CRP [receiver operating characteristic (ROC)-area 0.77 (95% confidence interval [CI]: 0.69-0.85)] and PCT [ROC-area 0.75 (95% CI: 0.67-0.83)] were both strong predictors of SBI. Duration of fever had no added diagnostic value to CRP and PCT. The Lab-score performed well [ROC area 0.79 (95% CI: 0.72-0.87)], but threshold values performed similar to often used cutoffs of single biomarkers. An updated Lab-score improved only moderately [ROC area 0.83 (95% CI: 0.76-0.90)]. PCT did not alter post-test probabilities for SBI substantially in patients with low (<20 mg/L) or elevated CRP (≥ 100 mg/L) levels (67% of population). CONCLUSION: CRP and PCT were both strong predictors of SBI. The original and updated Lab-score performed well, but thresholds values lacked diagnostic value for ruling out SBI. Depending on clinical risk thresholds, diagnostic testing can be limited to CRP or PCT, rather than both, in many febrile children.

Efficacy of fluticasone propionate on lung function and symptoms in wheezy infants.

The role of inhaled corticosteroids in the treatment of recurrent or persistent wheeze in infancy remains unclear. We evaluated the effect of 3 months of treatment with inhaled fluticasone propionate, 200 microg daily (FP200), on lung function and symptom scores in wheezy infants. Moreover, we evaluated whether infants with atopy and/or eczema respond better to FP200 as compared with non-atopic infants. Forced expiratory flow (Vmax(FRC)) was measured at baseline and after treatment. Sixty-five infants were randomized to receive FP200 or placebo, and 62 infants (mean age, 11.3 months) completed the study. Mean Vmax(FRC), expressed as a Z score, was significantly below normal at baseline and after treatment in both groups. The change from baseline of Vmax(FRC) was not different between the two treatment arms. After 6 weeks of treatment, and not after 13 weeks, the FP200 group had a significantly higher percentage of symptom-free days and a significant reduction in mean daily cough score compared with placebo. Separate analysis of treatment effect in infants with atopy or eczema showed no effect modification. We conclude that in wheezy infants, after 3 months of treatment with fluticasone, there was no improvement in lung function and no reduction in respiratory symptoms compared with placebo.