Browsing by Author "Nijman, Ruud G."

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    Availability and use of rapid diagnostic tests for the management of acute childhood infections in Europe : A cross-sectional survey of paediatricians
    (2022-12) Dewez, Juan Emmanuel; Pembrey, Lucy; Nijman, Ruud G.; del Torso, Stefano; Grossman, Zachi; Hadjipanayis, Adamos; Van Esso, Diego; Lim, Emma; Emonts, Marieke; Burns, James; Gras-LeGuen, Christèle; Kohlfuerst, Daniela; Dornbusch, Hans Jürgen; Brengel-Pesce, Karen; Mallet, Francois; von Both, Ulrich; Tsolia, Maria; Eleftheriou, Irini; Zavadska, Dace; de Groot, Ronald; van der Flier, Michiel; Moll, Henriëtte; Hagedoorn, Nienke; Borensztajn, Dorine; Oostenbrink, Rianne; Kuijpers, Taco; Pokorn, Marko; Vincek, Katarina; Martinó n-Torres, Federico; Rivero, Irene; Agyeman, Philipp; Carrol, Enitan D.; Paulus, Stéphane; Cunnington, Aubrey; Herberg, Jethro; Levin, Michael; Mujkić, Aida; Geitmann, Karin; Da Dalt, Liviana; Valiulis, Arunas; Lapatto, Risto; Syridou, Garyfallia; Altorjai, Péter; Torpiano, Paul; Størdal, Ketil; Illy, Károly; Mazur, Artur; Spreitzer, Mateja Vintar; Rios, Joana; Wyder, Corinne; Romankevych, Ivanna; Basmaci, Romain; Ibanez-Mico, Salvador; Yeung, Shunmay
    Background Point-of-care-tests (POCTs) have been advocated to optimise care in patients with infections but their actual use varies. This study aimed to estimate the variability in the adoption of current POCTs by paediatricians across Europe, and to explore the determinants of variability. Methods and findings A cross-sectional survey was conducted of hospital and primary care paediatricians, recruited through professional networks. Questions focused on the availability and use of currently available POCTs. Data were analysed descriptively and using Median Odds Ratio (MOR) to measure variation between countries. Multilevel regression modelling using changes in the area under the receiver operating characteristic curve of models were used to assess the contribution of individual or workplace versus country level factors, to the observed variation. The commonest POCT was urine dipsticks (UD) which were available to >80% of primary care and hospital paediatricians in 68% (13/19) and 79% (23/29) countries, respectively. Availability of all POCTs varied between countries. In primary care, the country (MOR) varied from 1.61 (95%CI: 1.04-2.58) for lactate to 7.28 (95%CI: 3.04-24.35) for UD. In hospitals, the country MOR varied from 1.37 (95%CI:1.04-1.80) for lactate to 11.93 (95% CI:3.35-72.23) for UD. Most paediatricians in primary care (69%, 795/1154) and hospital (81%, 962/1188) would use a diagnostic test in the case scenario of an infant with undifferentiated fever. Multilevel regression modelling showed that the country of work was more important in predicting both the availability and use of POCTs than individual or workplace characteristics. Conclusion There is substantial variability in the adoption of POCTs for the management of acute infections in children across Europe. To inform future implementation of both existing and innovative tests, further research is needed to understand what drives the variation between countries, the needs of frontline clinicians, and the role of diagnostic tests in the management of acute childhood infections.
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    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 Paediatrics
    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.
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    A Novel Framework for Phenotyping Children With Suspected or Confirmed Infection for Future Biomarker Studies
    (2021-07-28) Nijman, Ruud G.; Zavadska, Dace; PERFORM consortium; Rīga Stradiņš University
    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.
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    Presentations of children to emergency departments across Europe and the COVID-19 pandemic : A multinational observational study
    (2022-08) Nijman, Ruud G.; Honeyford, Kate; Farrugia, Ruth; Pučuka, Zanda; the REPEM network (Research in European Pediatric Emergency Medicine) as part of the EPISODES study group; Rīga Stradiņš University
    Background During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses. Methods and findings Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes. Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems. Conclusions Reductions in ED attendances were seen across Europe during the first COVID-19 lockdown period. More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell.
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    Sex differences in febrile children with respiratory symptoms attending European emergency departments : An observational multicenter study
    (2022-08-03) Tan, Chantal D.; el Ouasghiri, Soufiane; von Both, Ulrich; Carrol, Enitan D.; 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; Vermont, Clementien L.; Zenz, Werner; Zavadska, Dace; Moll, Henriette A.; Zachariasse, Joany M.; Department of Paediatrics
    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.
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    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 Paediatrics
    OBJECTIVES: 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.