Silvia Bressan

Procalcitonin and C-reactive protein as diagnostic markers of severe bacterial infections in febrile infants and children in the emergency department.

Objective: To assess the value of procalcitonin (PCT) and C-reactive protein (CRP), compared with that of total white-blood cell count (WBC) and absolute neutrophil count (ANC), in predicting severe bacterial infections (SBIs) in febrile children admitted to Emergency Department. Methods: A prospective study was conducted in 408 children aged 7-days to 36-months, admitted with fever without source, at a tertiary care Pediatric Emergency Department. PCT, CRP, WBC, and ANC were determined upon admission and compared. Specificity, sensitivity, multilevel likelihood ratios, receiver operating characteristic (ROC) analysis, and multivariate stepwise logistic regression were carried out. Results: SBI was diagnosed in 94 children (23.1%). PCT, CRP, WBC, and ANC were significantly higher in this group than in non-SBI patients. The area under the ROC (AUC) obtained was 0.82 (95% CI: 0.78–0.86) for PCT, 0.85 (95% CI: 0.81–0.88) for CRP (P = 0.358), 0.71 (95% CI: 0.66–0.75) for WBC, and 0.74 (95% CI: 0.70–0.78) for ANC. Only PCT (OR: 1.32; 95% CI: 1.11–1.57; P < 0.001) and CRP (OR: 1.02; 95% CI: 1.01–1.03; P < 0.001) were retained as significant predictors of SBI in a multiple regression model. For infants with fever <8 hours (n = 45), AUC for PCT and CRP were 0.92 (95% CI: 0.80–0.98) and 0.75 (95% CI: 0.60–0.87), respectively (P = 0.056). Conclusion: Both PCT and CRP are valuable markers in predicting SBI in children with fever without source and they perform better than WBC and ANC. PCT appears more accurate at the beginning of infections, but overall CRP may be the most convenient marker for its better sensitivity and feasibility.

Diagnostic Value of Procalcitonin in Well-Appearing Young Febrile Infants

BACKGROUND AND OBJECTIVE: Procalcitonin (PCT) has been introduced in many European protocols for the management of febrile children. Its value among young, well-appearing infants, however, is not completely defined. Our objective was to assess its performance in diagnosing serious bacterial infections and specifically invasive bacterial infections (IBIs) in well-appearing infants aged <3 months with fever without source (FWS). METHODS: Well-appearing infants aged <3 months with FWS admitted to 7 European pediatric emergency departments were retrospectively included. IBI was defined as the isolation of a bacterial pathogen in blood or cerebrospinal fluid culture. RESULTS: We included 1112 infants who had PCT measured and a blood culture performed. IBI was diagnosed in 23 cases (2.1%). In the multivariate analysis including clinical and laboratory data, PCT was the only independent risk factor for IBI (odds ratio 21.69; 95% confidence interval [CI] 7.93–59.28 for PCT ≥0.5 ng/mL). Positive likelihood ratios for PCT ≥2 ng/mL and C-reactive protein (CRP) >40 mg/L were 11.14 (95% CI 7.81–15.89) and 3.45 (95% CI 2.20–5.42), respectively. Negative likelihood ratios for PCT <0.5 ng/mL and CRP <20 mg/L were 0.25 (95% CI 0.12–0.55) and 0.41 (95% CI 0.22–0.76). Among patients with normal urine dipstick results and fever of recent onset, areas under the receiver operator characteristic curve for PCT and CRP were 0.819 and 0.563, respectively. CONCLUSIONS: Among well-appearing young infants with FWS, PCT performs better than CRP in identifying patients with IBIs and seems to be the best marker for ruling out IBIs. Among patients with normal urine dipstick results and fever of recent onset, PCT remains the most accurate blood test.

Association of Procalcitonin With Acute Pyelonephritis and Renal Scars in Pediatric UTI

BACKGROUND AND OBJECTIVE: Urinary tract infections (UTIs) are common childhood bacterial infections that may involve renal parenchymal infection (acute pyelonephritis [APN]) followed by late scarring. Prompt, high-quality diagnosis of APN and later identification of children with scarring are important for preventing future complications. Examination via dimercaptosuccinic acid scanning is the current clinical gold standard but is not routinely performed. A more accessible assay could therefore prove useful. Our goal was to study procalcitonin as a predictor for both APN and scarring in children with UTI. METHODS: A systematic review and meta-analysis of individual patient data were performed; all data were gathered from children with UTIs who had undergone both procalcitonin measurement and dimercaptosuccinic acid scanning. RESULTS: A total of 1011 patients (APN in 60.6%, late scarring in 25.7%) were included from 18 studies. Procalcitonin as a continuous, class, and binary variable was associated with APN and scarring (P < .001) and demonstrated a significantly higher (P < .05) area under the receiver operating characteristic curve than either C-reactive protein or white blood cell count for both pathologies. Procalcitonin ≥0.5 ng/mL yielded an adjusted odds ratio of 7.9 (95% confidence interval [CI]: 5.8–10.9) with 71% sensitivity (95% CI: 67–74) and 72% specificity (95% CI: 67–76) for APN. Procalcitonin ≥0.5 ng/mL was significantly associated with late scarring (adjusted odds ratio: 3.4 [95% CI: 2.1–5.7]) with 79% sensitivity (95% CI: 71–85) and 50% specificity (95% CI: 45–54). CONCLUSIONS: Procalcitonin was a more robust predictor compared with C-reactive protein or white blood cell count for selectively identifying children who had APN during the early stages of UTI, as well as those with late scarring.

Implementation of Adapted PECARN Decision Rule for Children With Minor Head Injury in the Pediatric Emergency Department

OBJECTIVES Of the currently published clinical decision rules for the management of minor head injury (MHI) in children, the Pediatric Emergency Care Applied Research Network (PECARN) rule, derived and validated in a large multicenter prospective study cohort, with high methodologic standards, appears to be the best clinical decision rule to accurately identify children at very low risk of clinically important traumatic brain injuries (ciTBI) in the pediatric emergency department (PED). This study describes the implementation of an adapted version of the PECARN rule in a tertiary care academic PED in Italy and evaluates implementation success, in terms of medical staff adherence and satisfaction, as well as its effects on clinical practice. METHODS The adapted PECARN decision rule algorithms for children (one for those younger than 2 years and one for those older than 2 years) were actively implemented in the PED of Padova, Italy, for a 6-month testing period. Adherence and satisfaction of medical staff to the new rule were calculated. Data from 356 visits for MHI during PECARN rule implementation and those of 288 patients attending the PED for MHI in the previous 6 months were compared for changes in computed tomography (CT) scan rate, ciTBI rate (defined as death, neurosurgery, intubation for longer than 24 hours, or hospital admission at least for two nights associated with TBI) and return visits for symptoms or signs potentially related to MHI. The safety and efficacy of the adapted PECARN rule in clinical practice were also calculated. RESULTS Adherence to the adapted PECARN rule was 93.5%. The percentage of medical staff satisfied with the new rule, in terms of usefulness and ease of use for rapid decision-making, was significantly higher (96% vs. 51%, p<0.0001) compared to the previous, more complex, internal guideline. CT scan was performed in 30 patients (8.4%, 95% confidence interval [CI]=6% to 11.8%) in the implementation period versus 21 patients (7.3%, 95% CI=4.8% to 10.9%) before implementation. A ciTBI occurred in three children (0.8%, 95% CI=0.3 to 2.5) during the implementation period and in two children (0.7%, 95% CI=0.2 to 2.5) in the prior 6 months. There were five return visits (1.4%) postimplementation and seven (2.4%) before implementation (p=0.506). The safety of use of the adapted PECARN rule in clinical practice was 100% (95% CI=36.8 to 100; three of three patients with ciTBI who received CT scan at first evaluation), while efficacy was 92.3% (95% CI=89 to 95; 326 of 353 patients without ciTBI who did not receive a CT scan). CONCLUSIONS The adapted PECARN rule was successfully implemented in an Italian tertiary care academic PED, achieving high adherence and satisfaction of medical staff. Its use determined a low CT scan rate that was unchanged compared to previous clinical practice and showed an optimal safety and high efficacy profile. Strict monitoring is mandatory to evaluate the long-lasting benefit in patient care and/or resource utilization.

Pediatric Emergency Care Applied Research Network head injury clinical prediction rules are reliable in practice

Objective The Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury (TBI) age-based clinical prediction rules identify children at very low risk of a significant head injury who can safely avoid CT. Our goal was to independently validate these prediction rules. Design Cross-sectional study. Setting Two paediatric emergency departments located in USA and in Italy. Patients All children presenting within 24 h of a head injury with a Glasgow Coma Score of ≥14. Intervention Assessment of PECARN TBI clinical predictors. Main outcome measure Clinically important TBI defined as head injury resulting in death, intubation for >24 h, neurosurgery or two or more nights of hospitalisation for the management of head trauma. Results During the study period, we included 2439 children (91% of eligible patients), of which 959 (39%) were <2 years of age and 1439 (59%) were male. Of the study patients, 373 (15%) had a CT performed, 69 (3%) had traumatic findings on their CT and 19 (0.8%) had a clinically important TBI. None of the children with a clinically important TBI were classified as very low risk by the PECARN TBI prediction rules (overall sensitivity 100%; 95% CI 83.2% to 100%, specificity 55%, 95% CI 52.5% to 56.6%, and negative predictive value 100%, 95% CI 99.6% to 100%). Conclusions In our external validation, the age-based PECARN TBI prediction rules accurately identified children at very low risk for a clinically significant TBI and can be used to assist CT decision making for children with minor blunt head trauma.

Procalcitonin is a Predictor for High-Grade Vesicoureteral Reflux in Children: Meta-Analysis of Individual Patient Data

OBJECTIVE To assess the predictive value of procalcitonin, a serum inflammatory marker, in the identification of children with first urinary tract infection (UTI) who might have high-grade (≥3) vesicoureteral reflux (VUR). STUDY DESIGN We conducted a meta-analysis of individual data, including all series of children aged 1 month to 4 years with a first UTI, a procalcitonin (PCT) level measurement, cystograms, and an early dimercaptosuccinic acid scan. RESULTS Of the 152 relevant identified articles, 12 studies representing 526 patients (10% with VUR ≥3) were included. PCT level was associated with VUR ≥3 as a continuous (P = .001), and as a binary variable, with a 0.5 ng/mL preferred threshold (adjusted OR, 2.5; 95% CI, 1.1 to 5.4). The sensitivity of PCT ≥0.5 ng/mL was 83% (95% CI, 71 to 91) with 43% specificity rate (95% CI, 38 to 47). In the subgroup of children with a positive results on dimercaptosuccinic acid scan, PCT ≥0.5 ng/mL was also associated with high-grade VUR (adjusted OR, 4.8; 95% CI, 1.3 to 17.6). CONCLUSIONS We confirmed that PCT is a sensitive and validated predictor strongly associated with VUR ≥3, regardless of the presence of early renal parenchymal involvement in children with a first UTI.

Bronchopulmonary dysplasia: The earliest and perhaps the longest lasting obstructive lung disease in humans

Bronchopulmonary dysplasia (BPD) is one of the most important sequelae of premature birth and the most common form of chronic lung disease of infancy. From a clinical standpoint BPD subjects are characterized by recurrent respiratory symptoms, which are very frequent during the first years of life and, although becoming less severe as children grow up, they remain more common than in term-born controls throughout childhood, adolescence and into adulthood. From a functional point of view BPD subjects show a significant airflow limitation that persists during adolescence and adulthood and they may experience an earlier and steeper decline in lung function during adulthood. Interestingly, patients born prematurely but not developing BPD usually fare better, but they too have airflow limitations during childhood and later on, suggesting that also prematurity per se has life-long detrimental effects on pulmonary function. For the time being, little is known about the presence and nature of pathological mechanisms underlying the clinical and functional picture presented by BPD survivors. Nonetheless, recent data suggest the presence of persistent neutrophilic airway inflammation and oxidative stress and it has been suggested that BPD may be sustained in the long term by inflammatory pathogenic mechanisms similar to those underlying COPD. This hypothesis is intriguing but more pathological data are needed. A better understanding of these pathogenetic mechanisms, in fact, may be able to orient the development of novel targeted therapies or prevention strategies to improve the overall respiratory health of BPD patients.

Validation of a laboratory risk index score for the identification of severe bacterial infection in children with fever without source

Objective The identification of severe bacterial infection (SBI)in children with fever without source (FWS) remains a diagnostic problem. The authors previously developed in their Swiss population a risk index score, called the Lab-score, associating three independent predictors of SBI, namely C reactive protein (CRP), procalcitonin (PCT) and urinary dipstick. The objective of this study was to validate the Lab-score in a population of children with FWS different from the derivation model. Methods A prospective study, conducted in Padova, on 408 children aged 7 days to 36 months with FWS was recently published. PCT, CRP, white blood cell count (WBC) and urinary dipstick were determined in all children. The Lab-score was applied to this population and the diagnostic characteristics for the detection of SBI were calculated for the Lab-score and for any single variable used in the Italian study. Results For the identification of SBI, the sensitivity of a score ≥3 was 86% (95% CI 77% to 92%) and the specificity 83% (95% CI 79% to 87%). The area under the receiver operating characteristic curve for the Lab-score (0.91) was significantly superior to that of any single variable: 0.71 for WBC, 0.86 for CRP and 0.84 for PCT. The Lab-score performed better than other laboratory markers, even when applied to children of different age groups (<3 months, 3–12 months and >12 months). The results obtained in this validation set population were comparable with those of the derivation set population. Conclusions This study validated the Lab-score as a valuable tool to identify SBI in children with FWS.

Diagnostic performance of the lab-score in predicting severe and invasive bacterial infections in well-appearing young febrile infants.

Background and Objectives: The “Lab-score” combining C-reactive protein, procalcitonin and urine dipstick results has recently been derived and validated as an accurate tool for predicting severe bacterial infections (SBIs) in children with fever without source. We aimed to assess the Lab-score usefulness in predicting SBI, especially invasive bacterial infections (IBIs), in well-appearing infants <3 months with fever without source. Methods: A multicenter retrospective study was conducted in 7 pediatric emergency departments in Spain and Italy. An SBI was defined as isolation of a bacterial pathogen from urine, blood, cerebrospinal fluid or stools, an IBI as isolation of a bacterial pathogen from blood or cerebrospinal fluid. The diagnostic characteristics of the Lab-score for detection of SBI and IBI were calculated. Results: An SBI was diagnosed in 287 (28.3%) of 1012 patients and an IBI in 23 (2.1%) of 1098. The positive and negative likelihood ratios of a score ≥3 for SBI prediction were 10.2 (95% confidence interval [CI]: 9.5–10.9) and 0.5 (95% CI: 0.5–0.5), respectively. The area under the receiver operating characteristic curve was 0.83 (95% CI: 0.80–0.86). The same diagnostic accuracy measures for identification of IBI were 4.3 (95% CI: 4–4.6), 0.4 (95% CI: 0.3–0.5) and 0.85 (95% CI: 0.76–0.94), respectively. Use of Lab-score would have resulted in misdiagnosis of 7 (30%) infants with IBI. Conclusions: In well-appearing infants with fever without source, the Lab-score seems a more useful tool for ruling in, rather than ruling out, SBI. Its accuracy for IBI prediction was unsatisfactory.

Accuracy of PECARN, CATCH, and CHALICE head injury decision rules in children: a prospective cohort study

BACKGROUND Clinical decision rules can help to determine the need for CT imaging in children with head injuries. We aimed to validate three clinical decision rules (PECARN, CATCH, and CHALICE) in a large sample of children. METHODS In this prospective observational study, we included children and adolescents (aged <18 years) with head injuries of any severity who presented to the emergency departments of ten Australian and New Zealand hospitals. We assessed the diagnostic accuracy of PECARN (stratified into children aged <2 years and ≥2 years), CATCH, and CHALICE in predicting each rule-specific outcome measure (clinically important traumatic brain injury [TBI], need for neurological intervention, and clinically significant intracranial injury, respectively). For each calculation we used rule-specific predictor variables in populations that satisfied inclusion and exclusion criteria for each rule (validation cohort). In a secondary analysis, we compiled a comparison cohort of patients with mild head injuries (Glasgow Coma Scale score 13-15) and calculated accuracy using rule-specific predictor variables for the standardised outcome of clinically important TBI. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614000463673. FINDINGS Between April 11, 2011, and Nov 30, 2014, we analysed 20 137 children and adolescents attending with head injuries. CTs were obtained for 2106 (10%) patients, 4544 (23%) were admitted, 83 (<1%) underwent neurosurgery, and 15 (<1%) died. PECARN was applicable for 4011 (75%) of 5374 patients younger than 2 years and 11 152 (76%) of 14 763 patients aged 2 years and older. CATCH was applicable for 4957 (25%) patients and CHALICE for 20 029 (99%). The highest point validation sensitivities were shown for PECARN in children younger than 2 years (100·0%, 95% CI 90·7-100·0; 38 patients identified of 38 with outcome [38/38]) and PECARN in children 2 years and older (99·0%, 94·4-100·0; 97/98), followed by CATCH (high-risk predictors only; 95·2%; 76·2-99·9; 20/21; medium-risk and high-risk predictors 88·7%; 82·2-93·4; 125/141) and CHALICE (92·3%, 89·2-94·7; 370/401). In the comparison cohort of 18 913 patients with mild injuries, sensitivities for clinically important TBI were similar. Negative predictive values in both analyses were higher than 99% for all rules. INTERPRETATION The sensitivities of three clinical decision rules for head injuries in children were high when used as designed. The findings are an important starting point for clinicians considering the introduction of one of the rules. FUNDING National Health and Medical Research Council, Emergency Medicine Foundation, Perpetual Philanthropic Services, WA Health Targeted Research Funds, Townsville Hospital Private Practice Fund, Auckland Medical Research Foundation, A + Trust.