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The study aimed to explore the use of diagnostics for febrile children presenting to European emergency departments (EDs), the determinants of inter-hospital variation, and the association between test use and hospitalization. We performed a secondary analysis of a cross-sectional observational study involving 28 paediatric EDs from 11 countries. A total of 4560 children < 16 years were included, with fever as reason for consultation. We excluded neonates and children with relevant comorbidities. Our primary outcome was the proportion of children receiving testing after primary evaluation, by country and by focus of infection. Variability between hospitals and effects of blood testing on patient disposition were explored by multilevel regression analyses, adjusting for patient characteristics (age group, triage level, appearance, fever duration, focus of infection) and hospital type (academic, teaching, other). The use of routine diagnostics varied widely, mostly in the use of blood tests, ranging from 3 to 75% overall across hospitals. Age < 3 months, high-acuity triage level, ill appearance, and suspicion of urinary tract infection displayed the strongest association with blood testing (odds ratios (OR) of 8.71 (95% CI 5.23-14.53), 19.46 (3.66-103.60), 3.13 (2.29-4.26), 10.84 (6.35-18.50), respectively). Blood testing remained highly variable across hospitals (median OR of the final model 2.36, 1.98-3.54). A positive association was observed between blood testing and hospitalization (OR 13.62, 9.00-20.61)., Conclusion: the use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. Focus groups of participating sites should help define reasons for unexpected variation., What Is Known: • Although previous research has shown variation in the emergency department (ED) management of febrile children, there is limited information on the use of diagnostics in European EDs. • A deeper knowledge of variability and its determinants can steer optimization of care., What Is New: • The use of diagnostics for febrile children was highly variable across European EDs, yet patient and hospital characteristics could only partly explain inter-hospital variability. • Data on between-centre comparison offer opportunities to further explore factors influencing unwarranted variation., (© 2022. The Author(s).)

Objective: To explore how parents judge disease severity of their febrile child and to identify symptoms they associate with serious illness, minor illness or health., Design: Semistructured interviews were conducted. Interviews were audio taped, transcribed verbatim and analysed thematically., Participants: Parents of children aged 0-5 years with a febrile illness., Setting: Participants were recruited at the paediatric ward and the emergency department., Results: Twenty-six interviews were conducted, in which 37 parents participated. Parents described disease severity of their child mainly in terms of changes in their child's normal characteristics (behaviour and physical features). They found it harder to describe specific disease symptoms such as dyspnoea or dehydration. Their child being active, eating and drinking well, and smiling were perceived as reassuring, whereas high fever, moving very little and uncertainty about the type of infections were mentioned as alarming symptoms. Previous experience with febrile illnesses in their children was of great influence on the number and accuracy of symptoms they reported., Conclusion: Parents used the normal behaviour and physical features of their child as a reference frame for judging disease severity. With a larger deviation from the child's normal characteristics, parents considered the illness more serious. They were less able to describe specific symptoms of disease such as dyspnoea or dehydration. This knowledge is important for clinicians in their communication with parents of children with febrile illness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Vital signs can help clinicians identify children at risk of serious illness. The NICE guideline for fever in under-fives recommends a routine measurement of temperature, heart rate, capillary refill and respiratory rate in all febrile children visiting the emergency department (ED). This study aims to evaluate the measurement of paediatric vital signs in European EDs, with specific attention to adherence to this NICE guideline recommendation. In a prospective observational study, we included 4560 febrile children under 16 years from the ED of 28 hospitals in 11 European countries (2014-2016). Hospitals were academic (n = 17), teaching (n = 10) and non-teaching (n = 1) and ranged in annual paediatric ED visits from 2700 to 88,000. Fifty-four percent were male, their median age was 2.4 years (IQR 1.1-4.7). Temperature was measured most frequently (97%), followed by capillary refill (86%), heart rate (73%), saturation (56%) and respiratory rate (51%). In children under five (n = 3505), a complete measurement of the four NICE-recommended vital signs was performed in 48% of patients. Children under 1 year of age, those with an urgent triage level and with respiratory infections had a higher likelihood of undergoing complete measurements. After adjustment for these factors, variability between countries remained. Conclusion: Measuring vital signs in children with fever in the ED occurs with a high degree of practice variation between different European hospitals, and adherence to the NICE recommendation is moderate. Our study is essential as a benchmark for current clinical practice, in order to tailor implementation strategies to different European settings.What is Known:• Vital signs can quickly provide information on disease severity in children in the emergency department (ED), and the NICE guideline for fever in under-fives recommends to routinely measure temperature, heart rate, capillary refill and respiratory rate.• Data regarding measurement of vital signs in routine practice across European EDs is currently unavailable.What is New:• Measurement of vital signs in febrile children is highly variable across European EDs and across patient subgroups, and compliance to the NICE recommendation is <50%.• Children under 1 year of age, those with an urgent triage level and with respiratory infections had a higher likelihood of undergoing complete measurements.

Background: Prevalence of serious bacterial infections in children in countries in western Europe and the USA is low. Antibiotic stewardship aims at a more rational use of antibiotics but information on the frequency of antibiotic prescription to children in emergency departments is scarce. We aimed to quantify and explain variability in antibiotic prescription in children attending European paediatric emergency departments., Methods: We did a cross-sectional, observational study of children aged between 1 month and 16 years who presented with fever to one of 28 European emergency departments on one random sampling day per month between Nov 1, 2014, and Feb 28, 2016. The surveyed sites were spread across 11 countries and included 17 academic hospitals with 3000 to up to 80 000 annual visits to their paediatric emergency departments. We determined the proportion of children without comorbidities who received antibiotic prescriptions by country, focus of infection, and type of antibiotic. We then did a detailed analysis of the same population, using a multilevel logistic regression analysis, into the variability in prescriptions across hospitals, focusing particularly on respiratory tract infections and correcting for a combination of result-dependent factors. Random group assignment was done by computer randomisation., Findings: Of 5177 children in total, 617 children had comorbidities. Of the 4560 children without comorbidities, 1454 (32%) received antibiotics. This percentage varied from 19% to 64% across countries. Of these 1454 prescriptions issued, 893 (61%) were second-line antibiotics. Antibiotic prescription for respiratory tract infections, the most common infection type, in children without comorbidities was most variable across countries (15-67% for upper respiratory tract infections and 24-87% for lower respiratory tract infections) and was associated with age (odds ratio [OR] 1·51, 95% CI 1·08-2·13), fever duration (OR 1·45, 1·01-2·07), blood concentrations of C-reactive protein (OR 2·31, 1·67-3·19), and chest x-ray results (OR 10·62, 5·65-19·94, for focal abnormalities; OR 3·49, 1·59-7·64, for diffuse abnormalities). After correcting for patient characteristics, diagnostic assessment, and hospital characteristics, antibiotic prescription for respiratory tract infections remained highly variable across emergency departments (standardised antibiotic prescription ratio 0·49-2·04)., Interpretation: Antibiotic prescription in European emergency departments is highly variable, with frequent use of second-line antibiotics. To ensure successful antibiotic stewardship initiatives in Europe aimed at reducing unnecessary prescription of antibiotics, variability of prescription across hospitals should be considered, drivers of suboptimal antibiotic prescription at the local level need to be identified, and European guidelines need to be devised., Funding: None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: First, to explore parents' views on and experiences of managing their febrile child and to assess their behaviour and needs when in search of information about fever; second, to develop and evaluate a hospital discharge information package about fever in children., Design: Mixed methods: (A) qualitative study with semistructured interviews and a focus group discussion (FGD) and (B) quantitative survey., Setting: Emergency department, non-acute hospital setting and day nursery in Rotterdam, The Netherlands., Participants: Parents of children <18 years (interviews, n=22) parents of children under 5 years (FGD (n=14), survey (n=38))., Intervention: Information package about fever in children (leaflet and website including videos)., Outcome Measures Quantitative Survey: Knowledge of fever and confidence in caring for a febrile child (Likert scale 0-5)., Results: Parents found fever mostly alarming, especially high fever. Help-seeking behaviour was based on either specific symptoms or on an undefined intuition. When parents did not feel recognised in their concern or felt criticised, anxiety increased as well as the threshold to seek healthcare for future illnesses. Information was needed, especially for situations when the general practitioner or social network were less easily available. This information should be reliable, consistent, available in multiple formats and include advice on management of fever at home and precise referral to medical services. Parents reported improved knowledge about fever (p<0.05) and mentioned improved confidence in caring for a child with fever at home after consulting the information package., Conclusion: Parents of children with a fever visiting the hospital are concerned about specific symptoms or based on an undefined intuition. Rather than telling parents that they should manage their child's illness at home, healthcare professionals should recognise parental intuition and provide clear information on alarming signs and potential diagnoses to empower parents in the management of their febrile child., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

Objective: To determine the agreement between peripheral and central capillary refill time (pCRT/cCRT) and their diagnostic values for detecting serious bacterial infection (SBI) in febrile children attending the paediatric emergency department (ED)., Design: Prospective observational study., Setting: Paediatric ED, Erasmus Medium Care-Sophia Children's hospital, the Netherlands., Patients: 1193 consecutively included, previously healthy, febrile children (1 month-16 years) with both pCRT measurements and cCRT measurements available. SBI diagnosis was based on abnormal radiographic findings and/or positive cultures from normally sterile locations in addition to clinical criteria., Main Outcome Measures: Agreement between pCRT and cCRT (Cohen's κ), overall and stratified for age and body temperature. The diagnostic value of pCRT and cCRT for SBI was assessed with logistic regression., Results: Overall agreement was 0.35 (95% CI 0.27 to 0.43; considered 'fair'). Although not significant, agreement was lower in children aged 1-<5 years (κ: 0.15 (95% CI 0.04 to 0.27)) and decreased with higher body temperatures with κ ranging from 0.55 (95% CI 0.32 to 0.79) for temperature <37.5°C to 0.21 (95% CI 0.07 to 0.34) for temperature >39.5°C. Abnormal pCRT (>2 s) was observed in 153 (12.8%; 95% CI 10.9% to 14.7%) and abnormal cCRT in 55 (4.6%; 95% CI 3.4% to 5.8%) children. The OR of abnormal pCRT (>2 s) for predicting SBI was 1.10 (95% CI 0.65 to 1.84). For abnormal cCRT (>2 s), the OR was 0.43 (95% CI 0.13 to 1.39)., Conclusions: The pCRT and cCRT values showed only fair agreement in a general population of febrile children at the ED, and no significant association with age or body temperature was found. Only a small part of febrile children at risk for serious infections at the ED show abnormal CRT values. Both abnormal pCRT and cCRT (defined as >2 s) performed poorly and were non-significant in this study detecting SBI in a general population of febrile children., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

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.

Background: C-Reactive protein (CRP) is an important diagnostic marker for serious bacterial infections in febrile children. C-Reactive protein bedside testing could potentially accelerate the diagnostic evaluation and shorten length of stay (LOS)., Objective: The aim of the study was to study the effect of introducing CRP bedside testing on the LOS of febrile children at the emergency department (ED)., Design and Intervention: A prospective observational study with a preimplementation cohort (2008) with traditional CRP testing and a postimplementation cohort (2009-2011) in which CRP bedside testing was introduced., Patients and Setting: All previously healthy children with fever, aged 1 month to 16 years, attending the ED of a university hospital were included; non-ill-appearing children with an upper airway infection were not eligible for CRP bedside testing., Analysis and Main Outcome Measure: Multivariable linear regression and propensity score analyses were used to determine the effect of CRP bedside testing on the logarithmic transformation length of stay [(log)LOS]., Results: The preimplementation cohort included 609 children of whom 286 (47%) had traditional CRP. The postimplementation cohort included the following 1330 children: 728 (55%) children had bedside CRP and 156 (12%) children had traditional CRP. Bedside CRP significantly lowered the median LOS of children in whom an additional diagnostic CRP test was performed, from 178 minutes (interquartile range, 135-232 minutes) to 148 minutes (interquartile range, 108-200 minutes) (30 minutes, 19% of total LOS). A significant reduction of 15% of the (log)LOS remained after adjusting for other determinants of (log)LOS; propensity score analysis showed a 16% reduction., Conclusions: C-Reactive protein bedside testing substantially lowered the LOS of children with fever at the ED in whom an additional diagnostic CRP test was performed.

Background: Clinical prediction rules (CPRs) to identify children with serious infections lack validation in low-prevalence populations, which hampers their implementation in primary care practice., Aim: To evaluate the diagnostic value of published CPRs for febrile children in primary care., Design and Setting: Observational cohort study among febrile children (<16 years) who consulted five GP cooperatives (GPCs) in the Netherlands., Method: Alarm signs of serious infection and clinical management were extracted from routine clinical practice data and manually recoded with a structured electronic data-entry program. Eight CPRs were selected from literature. CPR-variables were matched with alarm signs and CPRs were applied to the GPC-population. 'Referral to emergency department (ED)' was used as a proxy outcome measure for 'serious infection'. CPR performance was assessed by calibration analyses, sensitivity, specificity, and area under the ROC-curve (ROC-area)., Results: A total of 9794 GPC-contacts were eligible, 54% male, median age 2.3 years (interquartile range 1.0-4.6 years) and 8.1% referred to ED. Frequencies of CPR-variables varied from 0.5% (cyanosis, drowsy) to 25% (temperature ≥40°C). Alarm signs frequently included in CPRs were 'ill appearance', 'inconsolable', and 'abnormal circulatory or respiratory signs'. The height of the CPR's predicted risks generally corresponded with being (or not being) referred to the ED in practice. However, calibration-slopes indicated that three CPRs underestimated the risk of serious infection in the GPC-population. Sensitivities ranged from 42% to 54%, specificities from 68% to 89%. ROC-areas ranged from 0.52 to 0.81, with best performance of CPRs for children aged <3 months., Conclusion: Published CPRs performed moderately well in the primary out-of-hours care population. Advice is given on how to improve translation of CPRs to primary care practice., (© British Journal of General Practice 2015.)

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.

Context: Febrile children in primary care have a low risk for serious infection. Although several alarming signs and symptoms are proposed to have predictive value for serious infections, most are based on research in secondary care. The frequency of alarming signs/symptoms has not been established in primary care; however, in this setting differences in occurrence may influence their predictive value for serious infections., Objective: To determine the frequency of alarming signs/symptoms in febrile children in primary care., Design: Observational cohort study. Clinical information was registered in a semi-structured way and manually recoded., Setting: General practitioners' out-of-hours service., Subjects: Face-to-face patient contacts concerning children (aged ≤16 years) with fever were eligible for inclusion., Main Outcome Measures: Frequency of 18 alarming signs and symptoms as reported in the literature., Results: A total of 10,476 patient contacts were included. The frequency of alarming signs/symptoms ranged from n = 1 (ABC instability; <0.1%) to n = 2,207 (vomiting & diarrhea; 21.1%). Of all children, 59.7% had one or more alarming signs and/or symptoms. Several alarming signs/symptoms were poorly registered with the frequency of missing information ranging from 1,347 contacts (temperature >40°C as reported by the parents; 12.9%) to 8,647 contacts (parental concern; 82.5%)., Conclusion: Although the prevalence of specific alarming signs/symptoms is low in primary care, ≥50% of children have one or more alarming signs/symptoms. There is a need to determine the predictive value of alarming signs/symptoms not only for serious infections in primary care, but as well for increased risk of a complicated course of the illness.

Background: The diagnostic value of alarm features of serious infections in low prevalence settings is unclear., Aim: To explore to what extent alarm features play a role in referral to the emergency department (ED) by GPs who face a febrile child during out-of-hours care., Design and Setting: Observational study using semi-structured, routine clinical practice data of febrile children (<16 years) presenting to GP out-of-hours care., Method: Logistic regression analyses were performed to assess the association between alarm features of serious infections (selected from two guidelines and one systematic review) and referral to the ED. Adherence to the guideline was explored by a 2×2 contingency table., Results: In total 794 (8.1%) of 9794 eligible patients were referred to the ED. Alarm signs most strongly associated with referral were 'age <1 month', 'decreased consciousness', 'meningeal irritation', and 'signs of dehydration'. Nineteen percent of 3424 children with a positive referral indication according to the guideline were referred to the ED. The majority of those not referred had only one or two alarm features present. A negative referral indication was adhered to for the majority of children. Still, in 20% of referred children, alarm features were absent., Conclusion: In contrast to guidance, GPs working in primary out-of-hours care seem more conservative in referring febrile children to the ED, especially if only one or two alarm features of serious infection are present. In addition, in 20% of referred children, alarm features were absent, which suggests that other factors may be important in decisions about referral of febrile children to the hospital ED.

Febrile children pose the diagnostic dilemma of distinguishing those with serious infections from the vast majority with self-limiting diseases at an early stage. Alarm symptoms can aid in assessing the probability of serious infections in febrile children. The combined absence of alarm symptoms is useful in ruling out serious infections. CRP and PCT values are important diagnostic markers in febrile children in hospital settings. Children without any alarm symptoms and low inflammatory markers can be treated conservatively, provided there are good instructions on reassessment. Children with amber alarm symptoms or mildly elevated inflammatory markers in whom a serious infection cannot be ruled out require clinical observation or ambulant follow-up; empirical parenteral antibiotic treatment should also be considered and easily accessible. Children with red alarm symptoms or highly elevated inflammatory markers deserve clinical observation. In children < 3 months, empirical parenteral antibiotic treatment is also indicated.

Objectives: To develop and validate a prediction model for the early identification of children with pneumonia in emergency care settings., Methods: This was a diagnostic study with derivation and validation of multivariate logistic regression models. This study was carried out on children aged 1 month-16 years presenting with fever and cough visiting the pediatric emergency department of the Erasmus MC-Sophia, Rotterdam, the Netherlands (derivation population, n=504); Pediatric Assessment Unit, University Hospitals Coventry and Warwickshire NHS Trust, UK (validation population 1, n=420); Accident & Emergency Department, Queen's Medical Centre, Nottingham, UK (validation population 2, n=366). The outcome pneumonia is defined by the presence of pulmonary consolidations on chest radiograph or follow-up., Results: In population 1, 78 (16%) children were diagnosed with pneumonia; in populations 2 and 3, this number was 58 (14%) and 27 (7%), respectively. A simple clinical decision rule on the basis of ill appearance, tachypnea, decreased oxygen saturation, and elevated serum C-reactive protein categorized children as being at a low (<5%) or a high (>16%) risk of pneumonia. The rule yielded a discriminative value of 0.79 (0.69-0.89) in the Rotterdam population and was validated well in the other two populations., Conclusion: The risk of pneumonia can be assessed using three key clinical characteristics - overall assessment of the severity of illness, breathing rate, and oxygen saturation. Serum C-reactive protein contributes to the prediction of an intermediate risk of pneumonia in children. Children with a low risk of developing pneumonia with vital signs in the normal range can be discharged with effective safety netting, requiring neither antibiotics nor radiographs.

Background: Although fever in children is often self-limiting, antibiotics are frequently prescribed for febrile illnesses. GPs may consider treating serious infections by prescribing antibiotics., Aim: To examine whether alarm signs and/or symptoms for serious infections are related to antibiotic prescription in febrile children in primary care., Design and Setting: Observational cohort study involving five GP out-of-hours services., Method: Clinical information was registered and manually recoded. Children (<16 years) with fever having a face-to-face contact with a GP were included. Children who were already using antibiotics or referred to secondary care were excluded. The relation between alarm signs and/or symptoms for serious infections and antibiotic prescription was tested using multivariate logistic regression., Results: Of the 8676 included patients (median age 2.4 years), antibiotics were prescribed in 3167 contacts (36.5%). Patient characteristics and alarm signs and/or symptoms positively related to antibiotic prescription were: increasing age (odds ratio [OR] = 1.03; 95% confidence interval [95% CI] = 1.02 to 1.05), temperature measured by GP (OR = 1.72; 95% CI = 1.59 to 1.86), ill appearance (OR = 3.93; 95% CI = 2.85 to 5.42), being inconsolable (OR = 2.27; 95% CI = 1.58 to 3.22), shortness of breath (OR = 2.58; 95% CI = 1.88 to 3.56), duration of fever (OR = 1.31; 95% CI = 1.26 to 1.35). Negative associations were found for neurological signs (OR = 0.45; 95% CI = 0.27 to 0.76), signs of urinary tract infection (OR = 0.63; 95% CI = 0.49 to 0.82), and vomiting and diarrhoea (OR = 0.65; 95% CI = 0.57 to 0.74). These variables explained 19% of the antibiotic prescriptions., Conclusion: Antibiotics are often prescribed for febrile children. These data suggest that treatment of a supposed serious bacterial infection is a consideration of GPs. However, the relatively low explained variation indicates that other considerations are also involved.

Objective: To derive, cross validate, and externally validate a clinical prediction model that assesses the risks of different serious bacterial infections in children with fever at the emergency department., Design: Prospective observational diagnostic study., Setting: Three paediatric emergency care units: two in the Netherlands and one in the United Kingdom., Participants: Children with fever, aged 1 month to 15 years, at three paediatric emergency care units: Rotterdam (n=1750) and the Hague (n=967), the Netherlands, and Coventry (n=487), United Kingdom. A prediction model was constructed using multivariable polytomous logistic regression analysis and included the predefined predictor variables age, duration of fever, tachycardia, temperature, tachypnoea, ill appearance, chest wall retractions, prolonged capillary refill time (>3 seconds), oxygen saturation <94%, and C reactive protein., Main Outcome Measures: Pneumonia, other serious bacterial infections (SBIs, including septicaemia/meningitis, urinary tract infections, and others), and no SBIs., Results: Oxygen saturation <94% and presence of tachypnoea were important predictors of pneumonia. A raised C reactive protein level predicted the presence of both pneumonia and other SBIs, whereas chest wall retractions and oxygen saturation <94% were useful to rule out the presence of other SBIs. Discriminative ability (C statistic) to predict pneumonia was 0.81 (95% confidence interval 0.73 to 0.88); for other SBIs this was even better: 0.86 (0.79 to 0.92). Risk thresholds of 10% or more were useful to identify children with serious bacterial infections; risk thresholds less than 2.5% were useful to rule out the presence of serious bacterial infections. External validation showed good discrimination for the prediction of pneumonia (0.81, 0.69 to 0.93); discriminative ability for the prediction of other SBIs was lower (0.69, 0.53 to 0.86)., Conclusion: A validated prediction model, including clinical signs, symptoms, and C reactive protein level, was useful for estimating the likelihood of pneumonia and other SBIs in children with fever, such as septicaemia/meningitis and urinary tract infections.

Objective: To determine how vital signs such as heart and respiratory rates should be included in prediction models for serious bacterial infections (SBIs) in febrile children., Study Design and Setting: Prospective observational study of 1,750 febrile children aged <16 years, visiting the emergency department of a university hospital; of them 13% (n = 222) had SBI. Common age-specific thresholds of heart and respiratory rates were used to define tachycardia and tachypnea. We compared seven strategies to handle vital signs as predictors of SBI (dichotomized or continuously in various ways)., Results: The dichotomous predictors, namely tachycardia and tachypnea, containing information on the vital sign and age showed limited value to predict the presence of SBI (area under the receiver operating characteristic curve [AUC (ROC)]: 0.53 for heart rate and 0.55 for respiratory rate). In comparison, a model with age as a single continuous predictor resulted in an AUC of 0.58. Models with age and one of the vital signs included continuously showed the highest AUC (heart rate: 0.60 and respiratory rate: 0.63)., Conclusion: Heart and respiratory rates should be maintained as continuous variables in model development to predict SBI in febrile children, as dichotomization results in information loss and lower predictive ability., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: To assess whether the flowcharts and discriminators of the Manchester Triage System (MTS) can be used as indicators of alarming signs of serious febrile illness to predict the risk of hospitalization for febrile children who present at the emergency department (ED)., Study Design: Observational study, which included 2455 children (<16 years) who came to the ED of a university hospital with fever as their main complaint (May 2007-July 2009). Alarming signs for serious febrile illness were matched with MTS flowcharts and discriminators. At triage, the percentage of alarming signs positive was calculated. The diagnostic ability of the percentage of alarming signs positive to identify children at risk of hospitalization was assessed by calculating positive and negative likelihood ratios., Results: Thirty percent of children had at least 1 alarming sign positive at triage. Twenty-three percent were hospitalized. Positive likelihood ratios of hospitalization were 5.0 (95% CI: 3.9-6.5) for children with >20% of alarming signs positive at triage and 12.0 (95% CI: 5.2-27.6) for those with >40% of alarming signs positive. Negative likelihood ratios were 0.8 (95% CI: 0.8-0.8) and 1.0 (95% CI: 0.9-1.0), respectively., Conclusions: By alternatively using the flowcharts and discriminators of the MTS as alarming signs, rather than urgency classifiers, the MTS can function as a simple, readily available tool to identify febrile children at risk of hospitalization early in the care process. This knowledge may help to improve ED throughput times as well as admission and discharge management at pediatric EDs., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Although the topic of identifying febrile children at risk of serious infections has been addressed by numerous research groups, identified predictors remain diverse and implementation of results in routine practice has been limited. The aim of this paper is to discuss the problems and challenges in advancing diagnostic research in febrile children., Methods: The characteristics and results of 35 studies identified from a systematic review on predictors for febrile children were evaluated., Results: Current diagnostic research is mainly performed in subpopulations, defined by age and temperature limits and in paediatric emergency settings, ignoring the role of primary care. It is characterised by a dichotomous approach of outcomes and a wide variability of potential predictors. Validation of results to other settings and impact studies of prediction rules on patient outcomes are scarce. In designing diagnostic studies on children suspected of serious infections focus is needed on all clinically relevant populations within the spectrum of primary care and emergency department settings. Consensus is also needed on the definition of fever, the concept of serious infection and the set of predictors to focus on. The heterogeneity of patients in different settings and countries stress the need for continuous updating of prediction rules in routine practice. Broad validation in different clinical settings and countries and impact analysis in routine care is essential., Conclusions: Scientists in the field of diagnosis of serious infection in children must agree on core design features to be incorporated in all studies in the area of diagnostic research in febrile children. This will improve evidence from future studies, and their generalisability and implementation in routine practice.

Objective: The goal of this study was to evaluate parents' capability to assess their febrile child's severity of illness and decision to present to the emergency department. We compared children referred by a general practitioner (GP) with those self-referred on the basis of illness-severity markers., Methods: This was a cross-sectional observational study conducted at the emergency departments of a university and a teaching hospital. GP-referred or self-referred children with fever (aged <16 years) who presented to the emergency department (2006-2008) were included. Markers for severity of illness were urgency according to the Manchester Triage System, diagnostic interventions, therapeutic interventions, and follow-up. Associations between markers and referral type were assessed by using logistic regression analysis. Subgroup analyses were performed for patients with the most common presenting problems that accompanied the fever (ie, dyspnea, gastrointestinal complaints, neurologic symptoms, fever without specific symptoms)., Results: Thirty-eight percent of 4609 children were referred by their GP and 62% were self-referred. GP-referred children were classified as high urgency (immediate/very urgent categories) in 46% of the cases and self-referrals in 45%. Forty-three percent of GP referrals versus 27% of self-referrals needed extensive diagnostic intervention, intravenous medication/aerosol treatment, hospitalization, or a combination of these (odds ratio: 2.0 [95% confidence interval: 1.75-2.27]). In all subgroups, high urgency was not associated with referral type. GP-referred and self-referred children with dyspnea had similar frequencies of illness-severity markers., Conclusions: Although febrile self-referred children were less severely ill than GP-referred children, many parents properly judged and acted on the severity of their child's illness. To avoid delayed or missed diagnoses, recommendations regarding interventions that would discourage self-referral to the emergency department should be reconsidered.

Objective: To evaluate the discriminative ability of the Manchester triage system (MTS) to identify serious bacterial infections (SBIs) in children with fever in the emergency department (ED) and to study the association between predictors of SBI and discriminators of MTS urgency of care., Methods: This prospective observational study included 1255 children with fever (1 month-16 years) attending the ED of the Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands in 2008-9. Triage urgency was determined with the MTS (urgency (U) level 1-5). The relationship between triage urgency and SBI was assessed with multivariable logistic regression, including effects of age, sex and temperature. Discriminative ability was assessed by receiver operating characteristic curve analysis., Results: SBI prevalence was 11% (n=131, 95% CI 9% to 12%). The discriminative value of the MTS for predicting SBI was 0.57 (95% CI 0.52 to 0.62), and the MTS did not contribute to a model including age, sex and temperature. The sensitivity of the MTS (U1-2 vs U3-5) to detect SBI was 0.42 (95% CI 0.33 to 0.51) and specificity was 0.69 (95% CI 0.66 to 0.72). MTS high urgency discriminators include several known predictors of SBI, such as fever, work of breathing, meningism and oxygen saturation, but apply to non-SBI children as well., Conclusion: The MTS has poor discriminative ability to predict the presence of SBIs in children presenting with fever to the paediatric ED. Important predictors of SBI are represented within the MTS, but are used in a different way to classify urgency.

Objective: The objective was to study parental fever management and attitude toward fever from the perspective of the child's ethnicity and age., Patients and Setting: Children with fever presenting at the pediatric emergency department (PED) of the Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands, in the period from February 2002 to March 2004., Design: Prospective observational., Main Outcome Measures: Parental fever attitude and management assessed by a questionnaire., Results: Two hundred eleven children with fever (median age, 1.2 years; interquartile range, 0.7-2.0 years) were included, of whom 108 (55%) were boys. One hundred fourteen children (54%) were self-referrals at the PED. Accompanying symptoms were reported in 95% (50% had > or = 3); median temperature measured at PED was 39.5 degrees C (interquartile range, 38.9 degrees C-40.8 degrees C). One hundred fifty-five parents (74%) had used antipyretics to reduce fever, and 155 parents (74%) were worried about fever and its possible complications. Differences between Dutch and non-Dutch ethnicities were seen in temperature-reducing techniques, self-referral, and parental anxiety of fever and its complications. Age did not influence parental fever attitude and management., Conclusions: For most children in our population, the use of antipyretics was justified, as the majority of our children visiting the PED for an acute febrile episode are young infants, in particular with a high degree of fever and accompanying symptoms. We confirm and extend previous findings of ethnicity influencing parental fever management.

Prediction models fitted with logistic regression often show poor performance when applied in populations other than the development population. Model updating may improve predictions. Previously suggested methods vary in their extensiveness of updating the model. We aim to define a strategy in selecting an appropriate update method that considers the balance between the amount of evidence for updating in the new patient sample and the danger of overfitting. We consider recalibration in the large (re-estimation of model intercept); recalibration (re-estimation of intercept and slope) and model revision (re-estimation of all coefficients) as update methods. We propose a closed testing procedure that allows the extensiveness of the updating to increase progressively from a minimum (the original model) to a maximum (a completely revised model). The procedure involves multiple testing with maintaining approximately the chosen type I error rate. We illustrate this approach with three clinical examples: patients with prostate cancer, traumatic brain injury and children presenting with fever. The need for updating the prostate cancer model was completely driven by a different model intercept in the update sample (adjustment: 2.58). Separate testing of model revision against the original model showed statistically significant results, but led to overfitting (calibration slope at internal validation = 0.86). The closed testing procedure selected recalibration in the large as update method, without overfitting. The advantage of the closed testing procedure was confirmed by the other two examples. We conclude that the proposed closed testing procedure may be useful in selecting appropriate update methods for previously developed prediction models. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background The diagnostic value of alarm features of serious infections in low prevalence settings is unclear. Aim explore to what extent alarm features play a role in referral to the emergency department (ED) by GPs who face a febrile child during out-of-hours care. Design and setting study using semi-structured, routine clinical practice data of febrile children (