Liviana Da Dalt

Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.

OBJECTIVES. Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. METHODS. The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. RESULTS. Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. CONCLUSIONS. For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.

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.

Antibiotic treatment for pyelonephritis in children: multicentre randomised controlled non-inferiority trial

Objective To compare the efficacy of oral antibiotic treatment alone with treatment started parenterally and completed orally in children with a first episode of acute pyelonephritis. Design Multicentre, randomised controlled, open labelled, parallel group, non-inferiority trial. Setting 28 paediatric units in north east Italy. Participants 502 children aged 1 month to <7 years with clinical pyelonephritis. Intervention Oral co-amoxiclav (50 mg/kg/day in three doses for 10 days) or parenteral ceftriaxone (50 mg/kg/day in a single parenteral dose) for three days, followed by oral co-amoxiclav (50 mg/kg/day in three divided doses for seven days). Main outcomes measures Primary outcome was the rate of renal scarring. Secondary measures of efficacy were time to defervescence (<37�C), reduction in inflammatory indices, and percentage with sterile urine after 72 hours. An exploratory subgroup analysis was conducted in the children in whom pyelonephritis was confirmed by dimercaptosuccinic acid (DMSA) scintigraphy within 10 days after study entry. Results Intention to treat analysis showed no significant differences between oral (n=244) and parenteral (n=258) treatment, both in the primary outcome (scarring scintigraphy at 12 months 27/197 (13.7%) v 36/203 (17.7%), difference in risk −4%, 95% confidence interval −11.1% to 3.1%) and secondary outcomes (time to defervescence 36.9 hours (SD 19.7) v 34.3 hours (SD 20), mean difference 2.6 (−0.9 to 6.0); white cell count 9.8�109/l (SD 3.5) v 9.5�109/l (SD 3.1), mean difference 0.3 (−0.3 to 0.9); percentage with sterile urine 185/186 v 203/204, risk difference −0.05% (−1.5% to 1.4%)). Similar results were found in the subgroup of 278 children with confirmed acute pyelonephritis on scintigraphy at study entry. Conclusions Treatment with oral antibiotics is as effective as parenteral then oral treatment in the management of the first episode of clinical pyelonephritis in children. Trial registration Clinical Trials NCT00161330.

Clinical Consequences of Rotavirus Acute Gastroenteritis in Europe, 2004-2005: The REVEAL Study

BACKGROUND The availability of comprehensive, up-to-date epidemiologic data would improve the understanding of the disease burden and clinical consequences of rotavirus gastroenteritis (RVGE) in Europe. METHODS During the 2004-2005 season, a prospective, multicenter, observational study was conducted in children <5 years of age in primary care, emergency department, and hospital settings in selected areas of Belgium, France, Germany, Italy, Spain, Sweden, and the United Kingdom. The clinical consequences of acute gastroenteritis (AGE) and RVGE were estimated. RESULTS The estimated percentage of children with rotavirus-positive AGE admitted to a hospital was 10.4%-36.0%, compared with 2.1%-23.5% of children with rotavirus-negative AGE. In France, Germany, Italy, Spain, and the United Kingdom, the relative risk of hospitalization was statistically significantly higher for children with rotavirus-positive AGE than for those with rotavirus-negative AGE. Children with rotavirus-positive AGE were more likely to have lethargy, fever, vomiting, and dehydration, and, therefore, more severe disease than were children with rotavirus-negative AGE. Dehydration was up to 5.5 times more likely in children with rotavirus-positive AGE than in those with rotavirus-negative AGE. CONCLUSIONS Rotavirus-positive AGE is more severe, causes more dehydration, and results in more emergency department consultations and hospitalizations than does rotavirus-negative AGE. Variations in the management of RVGE seen across study areas could be explained by differences in health care systems. Routine rotavirus vaccination of infants could significantly reduce the substantial burden of RVGE and would have major benefits for potential patients, their families, and health care providers.

Predictors of intracranial injuries in children after blunt head trauma

This study was conducted to determine if clinical features can predict the risk of intracranial injury (ICI) in pediatric closed head trauma. We enrolled 3,806 children under 16 years consecutively referred for acute closed head trauma to the paediatric emergency room of five Italian children’s hospitals. Relevant outcomes were death and diagnosis of ICI. Clinical symptoms and signs were evaluated as possible outcome predictors. Children were also classified into five groups according to their clinical presentation. The association of ICI with signs and symptoms and the appropriateness of the five-group classification in predicting the likelihood of ICI were evaluated by logistic regression analyses. ICI was diagnosed in 22 children; 2 of them died. The risk of fatal and nonfatal ICI was 0.5 and 5.2 per 1,000 children with closed head trauma respectively. Significant associations were found between ICI and loss of consciousness, prolonged headache, persistent drowsiness, abnormal mental status, focal neurological signs, signs of skull fracture in non-frontal areas and signs of basal skull fracture. The five-group classification of children allowed an excellent prediction in terms of likelihood of ICI (ROC area 0.972). Conclusions: Selection of children with closed head trauma based on different combinations of signs and symptoms allows for early identification of subjects at different risk for ICI. In patients with minor head injuries, the absence of loss of consciousness, drowsiness, amnesia, prolonged headache, clinical evidence of basal or non-frontal skull fracture identified 100% of children without lesions. Validation of our results with a larger sample of patients with ICI would be highly desirable.

Visual outcome of a cohort of children with neurofibromatosis type 1 and optic pathway glioma followed by a pediatric neuro-oncology program

We evaluated the visual outcome of a cohort of children with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG) treated according to standardized therapeutic guidelines. The study population consisted of all consecutive patients with NF1 and OPG referred to a specialized pediatric neuro-oncology program between 1994 and 2004. Treatment was instituted only in cases of progressive disease or clinical deterioration. Treatment modalities were chemotherapy (based on vincristine/carboplatin) for children younger than 5 years and radiotherapy for all others. Ten boys and 10 girls (seven with a positive family history) entered the trial (median age at diagnosis of OPG, 29 months). At a median follow-up time of 78 months, seven patients had been treated with chemotherapy only, four with radiotherapy, and four with chemotherapy plus radiotherapy. Five patients were observed only. Currently, 18 are alive and two have died. Eight patients were treated for progressive visual loss in the face of stable disease, five for tumor volume increase without visual deterioration, and two for symptomatic tumor volume increase. At referral, six children had a visual acuity (VA) of < 30% in both eyes; eight children had 100% VA bilaterally. At referral, the visual field (VF) could be assessed in three children: One had VF loss in both eyes, one had VF loss in one eye, and one had normal VF. At last follow-up, eight children had VA < 20% in both eyes; only two children had 100% VA in both eyes. Among 11 children who had some visual function, three had VF loss in one eye and three in both eyes, and five had an intact VF. Contrast and color sensitivity were abnormal in seven and six patients, respectively. Thirteen children fell into the WHO hypovision category. In summary, among the 15 children treated, one had a definitive and two a mild improvement in VA. In conclusion, the visual outcome of this selected cohort of NF1 patients with OPG is unsatisfactory. A critical reappraisal of the therapeutic strategy adopted is needed.

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.

Identification of Children and Adolescents at Risk for Renal Scarring After a First Urinary Tract Infection: A Meta-analysis With Individual Patient Data

IMPORTANCE No studies have systematically examined the accuracy of clinical, laboratory, and imaging variables in detecting renal scarring in children and adolescents with a first urinary tract infection. OBJECTIVES To identify independent prognostic factors for the development of renal scarring and to combine these factors in prediction models that could be useful in clinical practice. DATA SOURCES MEDLINE and EMBASE. STUDY SELECTION We included patients aged 0 to 18 years with a first urinary tract infection who underwent follow-up renal scanning with technetium Tc 99m succimer at least 5 months later. DATA EXTRACTION AND SYNTHESIS We pooled individual patient data from 9 cohort studies. MAIN OUTCOMES AND MEASURES We examined the association between predictor variables assessed at the time of the first urinary tract infection and the development of renal scarring. Renal scarring was defined by the presence of photopenia on the renal scan. We assessed the following 3 models: clinical (demographic information, fever, and etiologic organism) and ultrasonographic findings (model 1); model 1 plus serum levels of inflammatory markers (model 2); and model 2 plus voiding cystourethrogram findings (model 3). RESULTS Of the 1280 included participants, 199 (15.5%) had renal scarring. A temperature of at least 39°C, an etiologic organism other than Escherichia coli, an abnormal ultrasonographic finding, polymorphonuclear cell count of greater than 60%, C-reactive protein level of greater than 40 mg/L, and presence of vesicoureteral reflux were all associated with the development of renal scars (P ≤ .01 for all). Although the presence of grade IV or V vesicoureteral reflux was the strongest predictor of renal scarring, this degree of reflux was present in only 4.1% of patients. The overall predictive ability of model 1 with 3 variables (temperature, ultrasonographic findings, and etiologic organism) was only 3% to 5% less than the predictive ability of models requiring a blood draw and/or a voiding cystourethrogram. Patients with a model 1 score of 2 or more (21.7% of the sample) represent a particularly high-risk group in whom the risk for renal scarring was 30.7%. At this cutoff, model 1 identified 44.9% of patients with eventual renal scarring. CONCLUSIONS AND RELEVANCE Children and adolescents with an abnormal renal ultrasonographic finding or with a combination of high fever (≥39°C) and an etiologic organism other than E coli are at high risk for the development of renal scarring.

Bacteremic Pneumococcal Community-acquired Pneumonia in Children Less Than 5 Years of Age in Italy

Background: This study was designed to determine the proportion of bacteremic pneumococcal cases in a group of pediatric subjects with community-acquired pneumonia (CAP), the importance of the different serotypes and the impact of the currently available pneumococcal conjugate vaccines (PCVs). Methods: The study involved children who were ⩽5 years with radiographically confirmed CAP admitted to hospital in Italy between September 2008 and March 2011. A diagnosis of laboratory-confirmed bacteremic pneumococcal CAP was made in the presence of a culture and/or real-time polymerase chain reaction (PCR) positive for Streptococcus pneumoniae. Results: A total of 510 children were included in the study. Pneumococcal CAP was diagnosed in 73 cases (14.3%): S. pneumoniae was identified by means of positive real-time PCR in 67 cases (91.8%), a positive blood culture in 1 (1.4%) and both in 5 (6.8%). Complicated pneumonia was observed significantly more often in the pneumococcal-positive cases (P = 0.02) and empyema was the main complication (P = 0.007). Serotype 19A was most frequently encountered (17 cases; 25.8%), followed by serotypes 14 (10 cases, 15.1%), 4 (5 cases, 7.6%) and 3 (4 cases, 6.1%). The theoretical coverage offered by the available PCVs was calculated to be 31% for PCV7, 37% for PCV10 and 71% for PCV13. Conclusions: In Italy, bacteremic pneumococcal CAP accounts for a significant number of CAP cases in children who were ⩽5 years, with serotypes 19A and 14 being the most frequent. This suggests that PCV13 is the best means of preventing pneumococcal CAP.