Ruud G. Nijman

Clinical prediction model to aid emergency doctors managing febrile children at risk of serious bacterial infections: diagnostic study.

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.

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

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

Parental fever attitude and management: influence of parental ethnicity and child's age.

Objective: The objective was to study parental fever management and attitude toward fever from the perspective of the childs ethnicity and age. Patients and Setting: Children with fever presenting at the pediatric emergency department (PED) of the Erasmus MC-Sophia Childrens 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 ≥3); median temperature measured at PED was 39.5°C (interquartile range, 38.9°C-40.8°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.

Can urgency classification of the Manchester triage system predict serious bacterial infections in febrile children

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 Childrens 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.

Vital signs should be maintained as continuous variables when predicting bacterial infections in febrile children

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.

C-Reactive Protein Bedside Testing in Febrile Children Lowers Length of Stay at the Emergency Department

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.

Comparison of peripheral and central capillary refill time in febrile children presenting to a paediatric emergency department and its utility in identifying children with serious bacterial infection.

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 Childrens 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 (Cohens 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.

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

Abstract 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 departement (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.

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

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

O-094 Diagnostic Usefulness Of Biomarkers In The Management Of Children With Fever At Risk Of Serious Bacterial Infections At The Emergency Department: Prospective Diagnostic Study

Background and aims To evaluate the diagnostic usefulness of biomarkers in the management of children with fever at risk of serious bacterial infections (SBI) at the emergency department (ED). Methods In this prospective observational study previously healthy children with fever, aged 1 month to 16 years, attending the EDs of a university hospital and a teaching hospital (Rotterdam, the Netherlands) between 2009 and 2012 were included. Standardised information on clinical signs and symptoms, C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD64 expression and urinalysis were collected prospectively. Logistic multivariable regression analysis was used to assess diagnostic performance. Results 1,084 children were included, median age was 1.6 years (interquartile range: 0.8–3.5), 170 children (16%) had SBI. CRP (receiver operating characteristic curve (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. CD64 lacked diagnostic strength (ROC-area 0.62 (95% CI 0.54–0.70)). A score containing PCT and CRP together with urinalysis, the Lab-score, performed well (ROC-area 0.79 (95% CI 0.72–0.87)), but thresholds performed similar to often used cut-offs of single biomarkers. Combined with clinical signs and symptoms both CRP and PCT were useful; additional PCT to CRP did not improve diagnostic performance substantially. Conclusions CRP and PCT were equally useful in the diagnostic evaluation of the febrile child, whereas CD64 wasn’t useful. Performing both CRP and PCT is often not indicated in a general population of febrile children. Our findings contrast previous studies suggesting PCT outperforming CRP and superior value of CD64 in specific settings.