Development and validation of an open-source pipeline for automatic population of case report forms from electronic health records: a pediatric multi-center prospective study.

BACKGROUND: Clinical trials and registry studies are essential for advancing research and developing novel treatments. However, these studies rely on manual entry of thousands of variables for each patient. Repurposing real-world data can significantly simplify the data collection, reduce transcription errors, and make the data entry process more efficient, consistent, and cost-effective. METHODS: We developed an open-source computational pipeline to collect laboratory and medication information from the electronic health record (EHR) data and populate case report forms. The pipeline was developed and validated with data from two independent pediatric hospitals in the US as part of the Long-terM OUtcomes after Multisystem Inflammatory Syndrome In Children (MUSIC) study. Our pipeline allowed the completion of two of the most time-consuming forms. We compared automatically extracted results with manually entered values in one hospital and applied the pipeline to a second hospital, where the output served as the primary data source for case report forms. FINDINGS: We extracted and populated 51,845 laboratory and 4913 medication values for 159 patients in two hospitals participating in a prospective pediatric study. We evaluated pipeline performance against data for 104 patients manually entered by clinicians in one of the hospitals. The highest concordance was found during patient hospitalization, with 91.59% of the automatically extracted laboratory and medication values corresponding with the manually entered values. In addition to the successfully populated values, we identified an additional 13,396 laboratory and 567 medication values of interest for the study. INTERPRETATION: The automatic data entry of laboratory and medication values during admission is feasible and has a high concordance with the manually entered data. By implementing this proof of concept, we demonstrate the quality of automatic data extraction and highlight the potential of secondary use of EHR data to advance medical science by improving data entry efficiency and expediting clinical research. FUNDING: NIH Grant 1OT3HL147154-01, U24HL135691, UG1HL135685.

The value of white blood cell count in predicting serious bacterial infections in children presenting to the emergency department: a multicentre observational study.

BACKGROUND: White blood cell count (WBC) is a widely used marker for the prediction of serious bacterial infection (SBI); however, previous research has shown poor performance. This study aims to assess the value of WBC in the prediction of SBI in children at the emergency department (ED) and compare its value with C reactive protein (CRP) and absolute neutrophil count (ANC). METHODS: This study is an observational multicentre study including febrile children aged 0-18 years attending 1 of 12 EDs in 8 European countries. The association between WBC and SBI was assessed by multivariable logistic regression, adjusting for age, CRP and duration of fever. Additionally, diagnostic performance was assessed by sensitivity and specificity. Results were compared with CRP and ANC. RESULTS: We included 17 082 children with WBC measurements, of which 1854 (10.9%) had an SBI. WBC >15 had an adjusted OR of 1.9 (95% CI 1.7 to 2.1) for prediction of SBI, after adjusting for confounders. Sensitivity and specificity were 0.56 (95% CI 0.54 to 0.58) and 0.74 (0.73 to 0.75) for WBC >15, and 0.32 (0.30 to 0.34) and 0.91 (0.91 to 0.91) for WBC >20, respectively. In comparison, CRP >20 mg/L had a sensitivity of 0.87 (95% CI 0.85 to 0.88) and a specificity of 0.59 (0.58 to 059). For CRP >80 mg/L, the sensitivity was 0.55 (95% CI 0.52 to 057) and the specificity was 0.91 (0.90 to 0.91). Additionally, for ANC >10, the sensitivity was 0.55 (95% CI 0.53 to 0.58) and the specificity was 0.75 (0.75 to 0.76). The combination of WBC and CRP did not improve performance compared with CRP alone. CONCLUSION: WBC does not have diagnostic benefit in identifying children with an SBI compared with CRP and should only be measured for specific indications.

Validation of the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in low- and middle-income countries: A multicentre observational study.

Early recognition of children at risk of serious illness is essential in preventing morbidity and mortality, particularly in low- and middle-income countries (LMICs). This study aimed to validate the Emergency Department-Paediatric Early Warning Score (ED-PEWS) for use in acute care settings in LMICs. This observational study is based on previously collected clinical data from consecutive children attending four diverse settings in LMICs. Inclusion criteria and study periods (2010-2021) varied. We simulated the ED-PEWS, consisting of patient age, consciousness, work of breathing, respiratory rate, oxygen saturation, heart rate, and capillary refill time, based on the first available parameters. Discrimination was assessed by the area under the curve (AUC), sensitivity and specificity (previously defined cut-offs < 6 and ≥ 15). The outcome measure was for each setting a composite marker of high urgency. 41,917 visits from Gambia rural, 501 visits from Gambia urban, 2,608 visits from Suriname, and 1,682 visits from Tanzania were included. The proportion of high urgency was variable (range 4.6% to 24.9%). Performance ranged from AUC 0.80 (95%CI 0.70-0.89) in Gambia urban to 0.62 (95%CI 0.55-0.67) in Tanzania. The low-urgency cut-off showed a high sensitivity in all settings ranging from 0.83 (95%CI 0.81-0.84) to 1.00 (95%CI 0.97-1.00). The high-urgency cut-off showed a specificity ranging from 0.71 (95%CI 0.66-0.75) to 0.97 (95%CI 0.97-0.97). The ED-PEWS has a moderate to good performance for the recognition of high urgency children in these LMIC settings. The performance appears to have potential in improving the identification of high urgency children in LMICs.

Which low urgent triaged febrile children are suitable for a fast track? An observational European study.

BACKGROUND: The number of paediatric patients visiting the ED with non-urgent problems is increasing, leading to poor patient flow and ED crowding. Fast track aims to improve the efficiency of evaluation and discharge of low acuity patients. We aimed to identify which febrile children are suitable for a fast track based on presenting symptoms and management. METHODS: This study is part of the Management and Outcome of Fever in children in Europe study, which is an observational study including routine data of febrile children <18 years attending 12 European EDs. We included febrile, low urgent children (those assigned a triage acuity of either 'standard' or 'non-urgent' using the Manchester Triage System) and defined children as suitable for fast track when they have minimal resource use and are discharged home. Presenting symptoms consisted of neurological (n=237), respiratory (n=8476), gastrointestinal (n=1953) and others (n=3473, reference group). Multivariable logistic regression analyses regarding presenting symptoms and management (laboratory blood testing, imaging and admission) were performed with adjustment for covariates: patient characteristics, referral status, previous medical care, previous antibiotic use, visiting hours and ED setting. RESULTS: We included 14 139 children with a median age of 2.7 years (IQR 1.3-5.2). The majority had respiratory symptoms (60%), viral infections (50%) and consisted of self-referrals (69%). The neurological group received imaging more often (adjusted OR (aOR) 1.8, 95% CI 1.1 to 2.9) and were admitted more frequently (aOR 1.9, 95% CI 1.4 to 2.7). The respiratory group had fewer laboratory blood tests performed (aOR 0.6, 95% CI 0.5 to 0.7), were less frequently admitted (aOR 0.6, 95% CI 0.5 to 0.7), but received imaging more often (aOR 1.8, 95% CI 1.6 to 2.0). Lastly, the gastrointestinal group had more laboratory blood tests performed (aOR 1.2. 95% CI 1.1 to 1.4) and were admitted more frequently (aOR 1.4, 95% CI 1.2 to 1.6). CONCLUSION: We determined that febrile children triaged as low urgent with respiratory symptoms were most suitable for a fast track. This study provides evidence for which children could be triaged to a fast track, potentially improving overall patient flow at the ED.

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES -1.18 years [95% CI -2.05, -0.32]), had fewer respiratory symptoms (RD -0.15 [95% CI -0.33, -0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD -0.35 [95% CI -0.64, -0.07]), lower lymphocyte count (ES -0.16 × 109/uL [95% CI -0.30, -0.01]), lower C-reactive protein (ES -28.5 mg/L [95% CI -46.3, -10.7]), and lower troponin (ES -0.14 ng/mL [95% CI -0.26, -0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES -1.6 years [95% CI -2.5, -0.8]), had less frequent SIRS (RD -0.18 [95% CI -0.30, -0.05]), lower lymphocyte count (ES -0.39 × 109/uL [95% CI -0.52, -0.25]), lower troponin (ES -0.16 ng/mL [95% CI -0.30, -0.01]) and less frequently received anticoagulation therapy (RD -0.19 [95% CI -0.37, -0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (-1.3 days [95% CI -2.3, -0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Emergency medical services utilisation among febrile children attending emergency departments across Europe: an observational multicentre study.

Children constitute 6-10% of all patients attending the emergency department (ED) by emergency medical services (EMS). However, discordant EMS use in children occurs in 37-61% with fever as an important risk factor. We aimed to describe EMS utilisation among febrile children attending European EDs. This study is part of an observational multicentre study assessing management and outcome in febrile children up to 18 years (MOFICHE) attending twelve EDs in eight European countries. Discordant EMS use was defined as the absence of markers of urgency including intermediate/high triage urgency, advanced diagnostics, treatment, and admission in children transferred by EMS. Multivariable logistic regression analyses were performed for the association between (1) EMS use and markers of urgency, and (2) patient characteristics and discordant EMS use after adjusting all analyses for the covariates age, gender, visiting hours, presenting symptoms, and ED setting. A total of 5464 (15%, range 0.1-42%) children attended the ED by EMS. Markers of urgency were more frequently present in the EMS group compared with the non-EMS group. Discordant EMS use occurred in 1601 children (29%, range 1-59%). Age and gender were not associated with discordant EMS use, whereas neurological symptoms were associated with less discordant EMS use (aOR 0.2, 95%CI 0.1-0.2), and attendance out of office hours was associated with more discordant EMS use (aOR 1.6, 95%CI 1.4-1.9). Settings with higher percentage of self-referrals to the ED had more discordant EMS use (p < 0.05).  Conclusion: There is large practice variation in EMS use in febrile children attending European EDs. Markers of urgency were more frequently present in children in the EMS group. However, discordant EMS use occurred in 29%. Further research is needed on non-medical factors influencing discordant EMS use in febrile children across Europe, so that pre-emptive strategies can be implemented. What is Known: •Children constitute around 6-10% of all patients attending the emergency department by emergency medical services. •Discordant EMS use occurs in 37-61% of all children, with fever as most common presenting symptom for discordant EMS use in children. What is New: •There is large practice variation in EMS use among febrile children across Europe with discordance EMS use occurring in 29% (range 1-59%), which was associated with attendance during out of office hours and with settings with higher percentage of self-referrals to the ED. •Future research is needed focusing on non-medical factors (socioeconomic status, parental preferences and past experience, healthcare systems, referral pathways, out of hours services provision) that influence discordant EMS use in febrile children across Europe.

Are children with prolonged fever at a higher risk for serious illness? A prospective observational study.

OBJECTIVES: To describe the characteristics and clinical outcomes of children with fever ≥5 days presenting to emergency departments (EDs). DESIGN: Prospective observational study. SETTING: 12 European EDs. PATIENTS: Consecutive febrile children <18 years between January 2017 and April 2018. INTERVENTIONS: Children with fever ≥5 days and their risks for serious bacterial infection (SBI) were compared with children with fever <5 days, including diagnostic accuracy of non-specific symptoms, warning signs and C-reactive protein (CRP; mg/L). MAIN OUTCOME MEASURES: SBI and other non-infectious serious illness. RESULTS: 3778/35 705 (10.6%) of febrile children had fever ≥5 days. Incidence of SBI in children with fever ≥5 days was higher than in those with fever <5 days (8.4% vs 5.7%). Triage urgency, life-saving interventions and intensive care admissions were similar for fever ≥5 days and <5 days. Several warning signs had good rule in value for SBI with specificities >0.90, but were observed infrequently (range: 0.4%-17%). Absence of warning signs was not sufficiently reliable to rule out SBI (sensitivity 0.92 (95% CI 0.87-0.95), negative likelihood ratio (LR) 0.34 (0.22-0.54)). CRP <20 mg/L was useful for ruling out SBI (negative LR 0.16 (0.11-0.24)). There were 66 cases (1.7%) of non-infectious serious illnesses, including 21 cases of Kawasaki disease (0.6%), 28 inflammatory conditions (0.7%) and 4 malignancies. CONCLUSION: Children with prolonged fever have a higher risk of SBI, warranting a careful clinical assessment and diagnostic workup. Warning signs of SBI occurred infrequently but, if present, increased the likelihood of SBI. Although rare, clinicians should consider important non-infectious causes of prolonged fever.

European study confirms the combination of fever and petechial rash as an important warning sign for childhood sepsis and meningitis.

AIM: This study investigated febrile children with petechial rashes who presented to European emergency departments (EDs) and investigated the role that mechanical causes played in diagnoses. METHODS: Consecutive patients with fever presenting to EDs in 11 European emergency departments in 2017-2018 were enrolled. The cause and focus of infection were identified and a detailed analysis was performed on children with petechial rashes. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We found that 453/34010 (1.3%) febrile children had petechial rashes. The focus of the infection included sepsis (10/453, 2.2%) and meningitis (14/453, 3.1%). Children with a petechial rash were more likely than other febrile children to have sepsis or meningitis (OR 8.5, 95% CI 5.3-13.1) and bacterial infections (OR 1.4, 95% CI 1.0-1.8) as well as need for immediate life-saving interventions (OR 6.6, 95% CI 4.4-9.5) and intensive care unit admissions (OR 6.5, 95% CI 3.0-12.5). CONCLUSION: The combination of fever and petechial rash is still an important warning sign for childhood sepsis and meningitis. Ruling out coughing and/or vomiting was insufficient to safely identify low-risk patients.

Sex differences in febrile children with respiratory symptoms attending European emergency departments: An observational multicenter study.

OBJECTIVE: To assess sex differences in presentation and management of febrile children with respiratory symptoms attending European Emergency Departments. DESIGN AND SETTING: An observational study in twelve Emergency Departments in eight European countries. PATIENTS: Previously healthy children aged 0-<18 years with fever (≥ 38°C) at the Emergency Department or in the consecutive three days before Emergency Department visit and respiratory symptoms were included. MAIN OUTCOME MEASURES: The main outcomes were patient characteristics and management defined as diagnostic tests, treatment and admission. Descriptive statistics were used for patient characteristics and management stratified by sex. Multivariable logistic regression analyses were performed for the association between sex and management with adjustment for age, disease severity and Emergency Department. Additionally, subgroup analyses were performed in children with upper and lower respiratory tract infections and in children below five years. RESULTS: We included 19,781 febrile children with respiratory symptoms. The majority were boys (54%), aged 1-5 years (58%) and triaged as low urgent (67%). Girls presented less frequently with tachypnea (15% vs 16%, p = 0.002) and increased work of breathing (8% vs 12%, p<0.001) compared with boys. Girls received less inhalation medication than boys (aOR 0.82, 95% CI 0.74-0.90), but received antibiotic treatment more frequently than boys (aOR 1.09, 95% CI 1.02-1.15), which is associated with a higher prevalence of urinary tract infections. Amongst children with a lower respiratory tract infection and children below five years girls received less inhalation medication than boys (aOR 0.77, 95% CI 0.66-0.89; aOR 0.80, 95% CI 0.72-0.90). CONCLUSIONS: Sex differences concerning presentation and management are present in previously healthy febrile children with respiratory symptoms presenting to the Emergency Department. Future research should focus on whether these differences are related to clinicians' attitudes, differences in clinical symptoms at the time of presentation and disease severity.

Febrile children with comorbidities at the emergency department - a multicentre observational study.

We aimed to describe characteristics and management of children with comorbidities attending European emergency departments (EDs) with fever. MOFICHE (Management and Outcome of Fever in children in Europe) is a prospective multicentre study (12 European EDs, 8 countries). Febrile children with comorbidities were compared to those without in terms of patient characteristics, markers of disease severity, management, and diagnosis. Comorbidity was defined as a chronic underlying condition that is expected to last > 1 year. We performed multivariable logistic regression analysis, displaying adjusted odds ratios (aOR), adjusting for patient characteristics. We included 38,110 patients, of whom 5906 (16%) had comorbidities. Most common comorbidities were pulmonary, neurologic, or prematurity. Patients with comorbidities more often were ill appearing (20 versus 16%, p < 0.001), had an ED-Paediatric Early Warning Score of > 15 (22 versus 12%, p < 0.001), or a C-reactive protein > 60 mg/l (aOR 1.4 (95%CI 1.3-1.6)). They more often required life-saving interventions (aOR 2.7, 95% CI 2.2-3.3), were treated with intravenous antibiotics (aOR 2.3, 95%CI 2.1-2.5), and were admitted to the ward (aOR 2.2, 95%CI 2.1-2.4) or paediatric intensive care unit (PICU) (aOR 5.5, 95% CI 3.8-7.9). They were more often diagnosed with serious bacterial infections (aOR 1.8, 95%CI 1.7-2.0), including sepsis/meningitis (aOR 4.6, 95%CI 3.2-6.7). Children most at risk for sepsis/meningitis were children with malignancy/immunodeficiency (aOR 14.5, 8.5-24.8), while children with psychomotor delay/neurological disease were most at risk for life-saving interventions (aOR 5.3, 4.1-6.9) or PICU admission (aOR 9.7, 6.1-15.5). CONCLUSIONS: Our data show how children with comorbidities are a population at risk, as they more often are diagnosed with bacterial infections and more often require PICU admission and life-saving interventions. WHAT IS KNOWN: • While children with comorbidity constitute a large part of ED frequent flyers, they are often excluded from studies. WHAT IS NEW: • Children with comorbidities in general are more ill upon presentation than children without comorbidities. • Children with comorbidities form a heterogeneous group; specific subgroups have an increased risk for invasive bacterial infections, while others have an increased risk of invasive interventions such as PICU admission, regardless of the cause of the fever.

Characteristics of pediatric emergency department frequent visitors and their risk of a return visit: A large observational study using electronic health record data.

BACKGROUND: Among pediatric emergency department (ED) visits, a subgroup of children repeatedly visits the ED, making them frequent visitors (FVs). The aim of this study is to get insight into the group of pediatric ED FVs and to determine risk factors associated with a revisit. METHODS AND FINDINGS: Data of all children aged 0-18 years visiting the ED of a university hospital in the Netherlands between 2017 and 2020 were included in this observational study based on routine data extraction. Children with 4 or more ED visits within 365 days were classified as FVs. Descriptive analysis of the study cohort at patient- and visit-level were performed. Risk factors for a recurrent ED visit were determined using a Prentice Williams and Peterson gap time cox-based model. Our study population of 10,209 children with 16,397 ED visits contained 500 FVs (4.9%) accounting for 3,481 visits (21.2%). At patient-level, FVs were younger and more often suffered from chronic diseases (CDs). At visit-level, frequent visits were more often initiated by self-referral and were more often related to medical problems (compared to trauma's). Overall, FVs presented at the ED more often because of an infection (41.3%) compared to non-FVs (27.4%), either associated or not with the body system affected by the CD. We identified the presence of a comorbidity (non-complex CD HR 1.66; 1.52-1.81 and complex CD HR 2.00; 1.84-2.16) as determinants with the highest hazard for a return visit. CONCLUSION: Pediatric ED FVs are a small group of children but account for a large amount of the total ED visits. FVs are younger patients, suffering from (complex) comorbidities and present more often with infectious conditions compared to non-FVs. Healthcare pathways, including safety-netting strategies for acute manifestations from their comorbidity, or for infectious conditions in general may contribute to support parents and redirect some patients from the ED.

Rapid Viral Testing and Antibiotic Prescription in Febrile Children With Respiratory Symptoms Visiting Emergency Departments in Europe.

BACKGROUND: Inappropriate antibiotic prescribing often occurs in children with self-limiting respiratory tract infections, contributing to antimicrobial resistance. It has been suggested that rapid viral testing can reduce inappropriate antibiotic prescribing. We aimed to assess the association between rapid viral testing at the Emergency Department (ED) and antibiotic prescription in febrile children. METHODS: This study is part of the MOFICHE study, which is an observational multicenter study including routine data of febrile children (0-18 years) attending 12 European EDs. In children with respiratory symptoms visiting 6 EDs equipped with rapid viral testing, we performed multivariable logistic regression analysis regarding rapid viral testing and antibiotic prescription adjusted for patient characteristics, disease severity, diagnostic tests, focus of infection, admission, and ED. RESULTS: A rapid viral test was performed in 1061 children (8%) and not performed in 11,463 children. Rapid viral test usage was not associated with antibiotic prescription (aOR 0.9, 95% CI: 0.8-1.1). A positive rapid viral test was associated with less antibiotic prescription compared with children without test performed (aOR 0.6, 95% CI: 0.5-0.8), which remained significant after adjustment for CRP and chest radiograph result. Twenty percent of the positively tested children received antibiotics. A negative rapid viral test was not associated with antibiotic prescription (aOR 1.2, 95% CI: 1.0-1.4). CONCLUSIONS: Rapid viral test usage did not reduce overall antibiotic prescription, whereas a positive rapid viral test did reduce antibiotic prescription at the ED. Implementation of rapid viral testing in routine emergency care and compliance to the rapid viral test outcome will reduce inappropriate antibiotic prescribing at the ED.

Multi-PheWAS intersection approach to identify sex differences across comorbidities in 59 140 pediatric patients with autism spectrum disorder.

OBJECTIVE: To identify differences related to sex and define autism spectrum disorder (ASD) comorbidities female-enriched through a comprehensive multi-PheWAS intersection approach on big, real-world data. Although sex difference is a consistent and recognized feature of ASD, additional clinical correlates could help to identify potential disease subgroups, based on sex and age. MATERIALS AND METHODS: We performed a systematic comorbidity analysis on 1860 groups of comorbidities exploring all spectrum of known disease, in 59 140 individuals (11 440 females) with ASD from 4 age groups. We explored ASD sex differences in 2 independent real-world datasets, across all potential comorbidities by comparing (1) females with ASD vs males with ASD and (2) females with ASD vs females without ASD. RESULTS: We identified 27 different comorbidities that appeared significantly more frequently in females with ASD. The comorbidities were mostly neurological (eg, epilepsy, odds ratio [OR] > 1.8, 3-18 years of age), congenital (eg, chromosomal anomalies, OR > 2, 3-18 years of age), and mental disorders (eg, intellectual disability, OR > 1.7, 6-18 years of age). Novel comorbidities included endocrine metabolic diseases (eg, failure to thrive, OR = 2.5, ages 0-2), digestive disorders (gastroesophageal reflux disease: OR = 1.7, 6-11 years of age; and constipation: OR > 1.6, 3-11 years of age), and sense organs (strabismus: OR > 1.8, 3-18 years of age). DISCUSSION: A multi-PheWAS intersection approach on real-world data as presented in this study uniquely contributes to the growing body of research regarding sex-based comorbidity analysis in ASD population. CONCLUSIONS: Our findings provide insights into female-enriched ASD comorbidities that are potentially important in diagnosis, as well as the identification of distinct comorbidity patterns influencing anticipatory treatment or referrals. The code is publicly available (https://github.com/hms-dbmi/sexDifferenceInASD).

Improving triage for children with comorbidity using the ED-PEWS: an observational study.

OBJECTIVE: To assess the value of the Emergency Department-Pediatric Early Warning Score (ED-PEWS) for triage of children with comorbidity. DESIGN: Secondary analysis of a prospective cohort. SETTING AND PATIENTS: 53 829 consecutive ED visits of children <16 years in three European hospitals (Netherlands, UK and Austria) participating in the TrIAGE (Triage Improvements Across General Emergency departments) project in different periods (2012-2015). INTERVENTION: ED-PEWS, a score consisting of age and six physiological parameters. MAIN OUTCOME MEASURE: A three-category reference standard as proxy for true patient urgency. We assessed discrimination and calibration of the ED-PEWS for children with comorbidity (complex and non-complex) and without comorbidity. In addition, we evaluated the value of adding the ED-PEWS to the routinely used Manchester Triage System (MTS). RESULTS: 5053 (9%) children had underlying non-complex morbidity and 5537 (10%) had complex comorbidity. The c-statistic for identification of high-urgency patients was 0.86 (95% prediction interval 0.84-0.88) for children without comorbidity, 0.87 (0.82-0.92) for non-complex and 0.86 (0.84-0.88) for complex comorbidity. For high and intermediate urgency, the c-statistic was 0.63 (0.62-0.63), 0.63 (0.61-0.65) and 0.63 (0.55-0.73) respectively. Sensitivity was slightly higher for children with comorbidity (0.73-0.75 vs 0.70) at the cost of a lower specificity (0.86-0.87 vs 0.92). Calibration was largely similar. Adding the ED-PEWS to the MTS for children with comorbidity improved performance, except in the setting with few high-urgency patients. CONCLUSIONS: The ED-PEWS has a similar performance in children with and without comorbidity. Adding the ED-PEWS to the MTS for children with comorbidity improves triage, except in the setting with few high-urgency patients.

Shock Index in the early assessment of febrile children at the emergency department: a prospective multicentre study.

OBJECTIVE: (1) To derive reference values for the Shock Index (heart rate/systolic blood pressure) based on a large emergency department (ED) population of febrile children and (2) to determine the diagnostic value of the Shock Index for serious illness in febrile children. DESIGN/SETTING: Observational study in 11 European EDs (2017-2018). PATIENTS: Febrile children with measured blood pressure. MAIN OUTCOME MEASURES: Serious bacterial infection (SBI), invasive bacterial infection (IBI), immediate life-saving interventions (ILSIs) and intensive care unit (ICU) admission. The association between high Shock Index (>95th centile) and each outcome was determined by logistic regression adjusted for age, sex, referral, comorbidity and temperature. Additionally, we calculated sensitivity, specificity and negative/positive likelihood ratios (LRs). RESULTS: Of 5622 children, 461 (8.2%) had SBI, 46 (0.8%) had IBI, 203 (3.6%) were treated with ILSI and 69 (1.2%) were ICU admitted. High Shock Index was associated with SBI (adjusted OR (aOR) 1.6 (95% CI 1.3 to 1.9)), ILSI (aOR 2.5 (95% CI 2.0 to 2.9)), ICU admission (aOR 2.2 (95% CI 1.4 to 2.9)) but not with IBI (aOR: 1.5 (95% CI 0.6 to 2.4)). For the different outcomes, sensitivity for high Shock Index ranged from 0.10 to 0.15, specificity ranged from 0.95 to 0.95, negative LRs ranged from 0.90 to 0.95 and positive LRs ranged from 1.8 to 2.8. CONCLUSIONS: High Shock Index is associated with serious illness in febrile children. However, its rule-out value is insufficient which suggests that the Shock Index is not valuable as a screening tool for all febrile children at the ED.

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.

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.

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.

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.