Browsing by Author "Hagedoorn, Nienke N."
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Item Characteristics and management of adolescents attending the ED with fever : A prospective multicentre study(2022-01-19) Borensztajn, Dorine; Hagedoorn, Nienke N.; Carrol, Enitan; Von Both, Ulrich; Dewez, Juan Emmanuel; Emonts, Marieke; Van Der Flier, Michiel; De Groot, Ronald; Herberg, Jethro; Kohlmaier, Benno; Levin, Michael; Lim, Emma; Maconochie, Ian; Martinon Torres, Federico; Nijman, Ruud; Pokorn, Marko; Rivero-Calle, Irene; Tsolia, Maria; Vermont, Clementien; Zavadska, Dace; Zenz, Werner; Zachariasse, Joany; Moll, Henriette A.; Department of PaediatricsObjective Most studies on febrile children have focused on infants and young children with serious bacterial infection (SBI). Although population studies have described an increased risk of sepsis in adolescents, little is known about febrile adolescents attending the emergency department (ED). We aimed to describe patient characteristics and management of febrile adolescents attending the ED. Design and setting The MOFICHE/PERFORM study (Management and Outcome of Febrile Children in Europe/Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union), a prospective multicentre study, took place at 12 European EDs. Descriptive and multivariable regression analyses were performed, comparing febrile adolescents (12-18 years) with younger children in terms of patient characteristics, markers of disease severity (vital signs, clinical alarming signs), management (diagnostic tests, therapy, admission) and diagnosis (focus, viral/bacterial infection). Results 37 420 encounters were included, of which 2577 (6.9%) were adolescents. Adolescents were more often triaged as highly urgent (38.9% vs 34.5%) and described as ill appearing (23.1% vs 15.6%) than younger children. Increased work of breathing and a non-blanching rash were present less often in adolescents, while neurological signs were present more often (1% vs 0%). C reactive protein tests were performed more frequently in adolescents and were more often abnormal (adjusted OR (aOR) 1.7, 95% CI 1.5 to 1.9). Adolescents were more often diagnosed with SBI (OR 1.8, 95% CI 1.6 to 2.0) and sepsis/meningitis (OR 2.3, 95% CI 1.1 to 5.0) and were more frequently admitted (aOR 1.3, 95% CI 1.2 to 1.4) and treated with intravenous antibiotics (aOR 1.7, 95% CI 1.5 to 2.0). Conclusions Although younger children presented to the ED more frequently, adolescents were more often diagnosed with SBI and sepsis/meningitis. Our data emphasise the importance of awareness of severe infections in adolescents.Item Development and validation of a prediction model for invasive bacterial infections in febrile children at European Emergency Departments : MOFICHE, a prospective observational study(2021-07-01) Hagedoorn, Nienke N.; Borensztajn, Dorine; Nijman, Ruud Gerard; Nieboer, Daan; Herberg, Jethro Adam; Balode, Anda; Von Both, Ulrich; Carrol, Enitan; Eleftheriou, Irini; Emonts, Marieke; Van Der Flier, Michiel; De Groot, Ronald; Kohlmaier, Benno; Lim, Emma; MacOnochie, Ian; Martinón-Torres, Federico; Pokorn, Marko; Strle, Franc; Tsolia, Maria; Zavadska, Dace; Zenz, Werner; Levin, Michael; Vermont, Clementien; Moll, Henriette A.; Rīga Stradiņš UniversityObjectives: To develop and cross-validate a multivariable clinical prediction model to identify invasive bacterial infections (IBI) and to identify patient groups who might benefit from new biomarkers. Design: Prospective observational study. Setting: 12 emergency departments (EDs) in 8 European countries. Patients: Febrile children aged 0-18 years. Main outcome measures: IBI, defined as bacteraemia, meningitis and bone/joint infection. We derived and cross-validated a model for IBI using variables from the Feverkidstool (clinical symptoms, C reactive protein), neurological signs, non-blanching rash and comorbidity. We assessed discrimination (area under the receiver operating curve) and diagnostic performance at different risk thresholds for IBI: sensitivity, specificity, negative and positive likelihood ratios (LRs). Results: Of 16 268 patients, 135 (0.8%) had an IBI. The discriminative ability of the model was 0.84 (95% CI 0.81 to 0.88) and 0.78 (95% CI 0.74 to 0.82) in pooled cross-validations. The model performed well for the rule-out threshold of 0.1% (sensitivity 0.97 (95% CI 0.93 to 0.99), negative LR 0.1 (95% CI 0.0 to 0.2) and for the rule-in threshold of 2.0% (specificity 0.94 (95% CI 0.94 to 0.95), positive LR 8.4 (95% CI 6.9 to 10.0)). The intermediate thresholds of 0.1%-2.0% performed poorly (ranges: sensitivity 0.59-0.93, negative LR 0.14-0.57, specificity 0.52-0.88, positive LR 1.9-4.8) and comprised 9784 patients (60%). Conclusions: The rule-out threshold of this model has potential to reduce antibiotic treatment while the rule-in threshold could be used to target treatment in febrile children at the ED. In more than half of patients at intermediate risk, sensitive biomarkers could improve identification of IBI and potentially reduce unnecessary antibiotic prescriptions.Item Diversity in the emergency care for febrile children in Europe : A questionnaire study(2019-06-01) Borensztajn, Dorine; Yeung, Shunmay; Hagedoorn, Nienke N.; Balode, Anda; Von Both, Ulrich; Carrol, Enitan D.; Dewez, Juan Emmanuel; Eleftheriou, Irini; Emonts, Marieke; Van Der Flier, Michiel; De Groot, Ronald; Herberg, Jethro Adam; Kohlmaier, Benno; Lim, Emma; MacOnochie, Ian; Martinón-Torres, Federico; Nijman, Ruud; Pokorn, Marko; Strle, Franc; Tsolia, Maria; Wendelin, Gerald; Zavadska, Dace; Zenz, Werner; Levin, Michael; Moll, Henriette A.; Department of PaediatricsObjective To provide an overview of care in emergency departments (EDs) across Europe in order to interpret observational data and implement interventions regarding the management of febrile children. Design and setting An electronic questionnaire was sent to the principal investigators of an ongoing study (PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management), www.perform2020.eu) in 11 European hospitals in eight countries: Austria, Germany, Greece, Latvia, the Netherlands, Slovenia, Spain and the UK. Outcome measures The questionnaire covered indicators in three domains: local ED quality (supervision, guideline availability, paper vs electronic health records), organisation of healthcare (primary care, immunisation), and local factors influencing or reflecting resource use (availability of point-of-care tests, admission rates). Results Reported admission rates ranged from 4% to 51%. In six settings (Athens, Graz, Ljubljana, Riga, Rotterdam, Santiago de Compostela), the supervising ED physicians were general paediatricians, in two (Liverpool, London) these were paediatric emergency physicians, in two (Nijmegen, Newcastle) supervision could take place by either a general paediatrician or a general emergency physician, and in one (München) this could be either a general paediatrician or a paediatric emergency physician. The supervising physician was present on site in all settings during office hours and in five out of eleven settings during out-of-office hours. Guidelines for fever and sepsis were available in all settings; however, the type of guideline that was used differed. Primary care was available in all settings during office hours and in eight during out-of-office hours. There were differences in routine immunisations as well as in additional immunisations that were offered; immunisation rates varied between and within countries. Conclusion Differences in local, regional and national aspects of care exist in the management of febrile children across Europe. This variability has to be considered when trying to interpret differences in the use of diagnostic tools, antibiotics and admission rates. Any future implementation of interventions or diagnostic tests will need to be aware of this European diversity.Item Febrile children with comorbidities at the emergency department — a multicentre observational study(2022-09) Borensztajn, Dorine M.; Hagedoorn, Nienke N.; Carrol, Enitan D.; von Both, Ulrich; Emonts, Marieke; van der Flier, Michiel; de Groot, Ronald; Herberg, Jethro; Kohlmaier, Benno; Levin, Michael; Lim, Emma; Maconochie, Ian K.; Martinon-Torres, Federico; Nijman, Ruud G.; Pokorn, Marko; Rivero-Calle, Irene; Tsolia, Maria; van der Velden, Fabian J.S.; Vermont, Clementien; Zavadska, Dace; Zenz, Werner; Zachariasse, Joany M.; Moll, Henriette A.; Department of PaediatricsWe 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.Item Impact of a clinical decision rule on antibiotic prescription for children with suspected lower respiratory tract infections presenting to European emergency departments : a simulation study based on routine data(2021-02-10) Hagedoorn, Nienke N.; Zavadska, Dace; PERFORM consortium; Rīga Stradiņš UniversityBACKGROUND: Discriminating viral from bacterial lower respiratory tract infections (LRTIs) in children is challenging thus commonly resulting in antibiotic overuse. The Feverkidstool, a validated clinical decision rule including clinical symptoms and C-reactive protein, safely reduced antibiotic use in children at low/intermediate risk for bacterial LRTIs in a multicentre trial at emergency departments (EDs) in the Netherlands. OBJECTIVES: Using routine data from an observational study, we simulated the impact of the Feverkidstool on antibiotic prescriptions compared with observed antibiotic prescriptions in children with suspected LRTIs at 12 EDs in eight European countries. METHODS: We selected febrile children aged 1 month to 5 years with respiratory symptoms and excluded upper respiratory tract infections. Using the Feverkidstool, we calculated individual risks for bacterial LRTI retrospectively. We simulated antibiotic prescription rates under different scenarios: (1) applying effect estimates on antibiotic prescription from the trial; and (2) varying both usage (50%-100%) and compliance (70%-100%) with the Feverkidstool's advice to withhold antibiotics in children at low/intermediate risk for bacterial LRTI (≤10%). RESULTS: Of 4938 children, 4209 (85.2%) were at low/intermediate risk for bacterial LRTI. Applying effect estimates from the trial, the Feverkidstool reduced antibiotic prescription from 33.5% to 24.1% [pooled risk difference: 9.4% (95% CI: 5.7%-13.1%)]. Simulating 50%-100% usage with 90% compliance resulted in risk differences ranging from 8.3% to 15.8%. Our simulations suggest that antibiotic prescriptions would be reduced in EDs with high baseline antibiotic prescription rates or predominantly (>85%) low/intermediate-risk children. CONCLUSIONS: Implementation of the Feverkidstool could reduce antibiotic prescriptions in children with suspected LRTIs in European EDs.Item Shock Index in the early assessment of febrile children at the emergency department : a prospective multicentre study(2022-02) Hagedoorn, Nienke N.; Zachariasse, Joany M.; Borensztajn, Dorine; Adriaansens, Elise; Von Both, Ulrich; Carrol, Enitan D.; Eleftheriou, Irini; Emonts, Marieke; Van Der Flier, Michiel; De Groot, Ronald; Herberg, Jethro Adam; Kohlmaier, Benno; Lim, Emma; Maconochie, Ian; Martinón-Torres, Federico; Nijman, Ruud Gerard; Pokorn, Marko; Rivero-Calle, Irene; Tsolia, Maria; Zavadska, Dace; Zenz, Werner; Levin, Michael; Vermont, Clementien; Moll, Henriette A.; Department of PaediatricsObjective: (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.Item Variation in antibiotic prescription rates in febrile children presenting to emergency departments across Europe (MOFICHE) : A multicentre observational study(2020-08-19) Hagedoorn, Nienke N.; Balode, Anda; Zavadska, Dace; PERFORM consortium; Rīga Stradiņš UniversityBackground The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. Methods and findings Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0–18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%–41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%–90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%–29.3%), and inconclusive in 22.5% (range across EDs: 0.4%–60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%–59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%–47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%–100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. Conclusions In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.Item Variation in hospital admission in febrile children evaluated at the Emergency Department (ED) in Europe : PERFORM, a multicentre prospective observational study(2021-01-07) Borensztajn, Dorine M.; Hagedoorn, Nienke N.; Calle, Irene Rivero; Maconochie, Ian K.; von Both, Ulrich; Carrol, Enitan D.; Dewez, Juan Emmanuel; Emonts, Marieke; van der Flier, Michiel; de Groot, Ronald; Herberg, Jethro; Kohlmaier, Benno; Lim, Emma; Martinon-Torres, Federico; Nieboer, Daan; Nijman, Ruud G.; Pokorn, Marko; Strle, Franc; Tsolia, Maria; Vermont, Clementien; Yeung, Shunmay; Zavadska, Dace; Zenz, Werner; Levin, Michael; Moll, Henriette A.; Department of PaediatricsOBJECTIVES: Hospitalisation is frequently used as a marker of disease severity in observational Emergency Department (ED) studies. The comparison of ED admission rates is complex in potentially being influenced by the characteristics of the region, ED, physician and patient. We aimed to study variation in ED admission rates of febrile children, to assess whether variation could be explained by disease severity and to identify patient groups with large variation, in order to use this to reduce unnecessary health care utilization that is often due to practice variation. DESIGN: MOFICHE (Management and Outcome of Fever in children in Europe, part of the PERFORM study, www.perform2020.org), is a prospective cohort study using routinely collected data on febrile children regarding patient characteristics (age, referral, vital signs and clinical alarming signs), diagnostic tests, therapy, diagnosis and hospital admission. SETTING AND PARTICIPANTS: Data were collected on febrile children aged 0-18 years presenting to 12 European EDs (2017-2018). MAIN OUTCOME MEASURES: We compared admission rates between EDs by using standardised admission rates after adjusting for patient characteristics and initiated tests at the ED, where standardised rates >1 demonstrate higher admission rates than expected and rates <1 indicate lower rates than expected based on the ED patient population. RESULTS: We included 38,120 children. Of those, 9.695 (25.4%) were admitted to a general ward (range EDs 5.1-54.5%). Adjusted standardised admission rates ranged between 0.6 and 1.5. The largest variation was seen in short admission rates (0.1-5.0), PICU admission rates (0.2-2.2), upper respiratory tract infections (0.4-1.7) and fever without focus (0.5-2.7). Variation was small in sepsis/meningitis (0.9-1.1). CONCLUSIONS: Large variation exists in admission rates of febrile children evaluated at European EDs, however, this variation is largely reduced after correcting for patient characteristics and therefore overall admission rates seem to adequately reflect disease severity or a potential for a severe disease course. However, for certain patient groups variation remains high even after adjusting for patient characteristics.