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Background: Community-acquired Pneumonia (CAP) is a common childhood infectious disease. Deep learning models show promise in X-ray interpretation and diagnosis, but their validation should be extended due to limitations in the current validation workflow. To extend the standard validation workflow we propose doing a pilot test with the next characteristics. First, the assumption of perfect ground truth (100% sensitive and specific) is unrealistic, as high intra and inter-observer variability have been reported. To address this, we propose using Bayesian latent class models (BLCA) to estimate accuracy during the pilot. Additionally, assessing only the performance of a model without considering its applicability and acceptance by physicians is insufficient if we hope to integrate AI systems into day-to-day clinical practice. Therefore, we propose employing explainable artificial intelligence (XAI) methods during the pilot test to involve physicians and evaluate how well a Deep Learning model is accepted and how helpful it is for routine decisions as well as analyze its limitations by assessing the etiology. This study aims to apply the proposed pilot to test a deep Convolutional Neural Network (CNN)-based model for identifying consolidation in pediatric chest-X-ray (CXR) images already validated using the standard workflow., Methods: For the standard validation workflow, a total of 5856 public CXRs and 950 private CXRs were used to train and validate the performance of the CNN model. The performance of the model was estimated assuming a perfect ground truth. For the pilot test proposed in this article, a total of 190 pediatric chest-X-ray (CXRs) images were used to test the CNN model support decision tool (SDT). The performance of the model on the pilot test was estimated using extensions of the two-test Bayesian Latent-Class model (BLCA). The sensitivity, specificity, and accuracy of the model were also assessed. The clinical characteristics of the patients were compared according to the model performance. The adequacy and applicability of the SDT was tested using XAI techniques. The adequacy of the SDT was assessed by asking two senior physicians the agreement rate with the SDT. The applicability was tested by asking three medical residents before and after using the SDT and the agreement between experts was calculated using the kappa index., Results: The CRXs of the pilot test were labeled by the panel of experts into consolidation (124/176, 70.4%) and no-consolidation/other infiltrates (52/176, 29.5%). A total of 31/176 (17.6%) discrepancies were found between the model and the panel of experts with a kappa index of 0.6. The sensitivity and specificity reached a median of 90.9 (95% Credible Interval (CrI), 81.2-99.9) and 77.7 (95% CrI, 63.3-98.1), respectively. The senior physicians reported a high agreement rate (70%) with the system in identifying logical consolidation patterns. The three medical residents reached a higher agreement using SDT than alone with experts (0.66±0.1 vs. 0.75±0.2)., Conclusions: Through the pilot test, we have successfully verified that the deep learning model was underestimated when a perfect ground truth was considered. Furthermore, by conducting adequacy and applicability tests, we can ensure that the model is able to identify logical patterns within the CXRs and that augmenting clinicians with automated preliminary read assistants could accelerate their workflows and enhance accuracy in identifying consolidation in pediatric CXR images., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain., Objectives: To provide recommendations for the administration of nirsevimab for prevention of RSV disease., Methods: The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions., Results: In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis., Conclusions: Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis., (Copyright © 2023 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Pneumonia is a frequent manifestation of coronavirus disease 2019 (COVID-19) in hospitalized children., Methods: The study involved 80 hospitals in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spanish Pediatric National Cohort. Participants were children <18 years, hospitalized with SARS-CoV-2 community-acquired pneumonia (CAP). We compared the clinical and radiological characteristics of SARS-CoV-2-associated CAP with CAP due to other viral etiologies from ValsDance (retrospective) cohort., Results: In total, 151 children with SARS-CoV-2-associated CAP and 138 with other viral CAP were included. Main clinical features of SARS-CoV-2-associated CAP were cough, fever, or dyspnea. Lymphopenia was found in 43% patients and 15% required admission to the pediatric intensive care unit (PICU). Chest X-ray revealed condensation (42%) and other infiltrates (58%). Compared with CAP from other viral pathogens, COVID-19 patients were older, with lower C-reactive protein (CRP) levels, less wheezing, and greater need of mechanical ventilation (MV). There were no differences in the use of continuous positive airway pressure (CPAP) or HVF, or PICU admission between groups., Conclusion: SARS-CoV-2-associated CAP in children presents differently to other virus-associated CAP: children are older and rarely have wheezing or high CRP levels; they need less oxygen but more CPAP or MV. However, several features overlap and differentiating the etiology may be difficult. The overall prognosis is good., (© 2022 Wiley Periodicals LLC.)

Background: Establishing the etiology of community-acquired pneumonia (CAP) in children at admission is challenging. Most of the admitted children with CAP receive antibiotics. We aimed to build and validate a diagnostic tool combining clinical, analytical and radiographic features to differentiate viral from bacterial CAP, and among bacterial CAP, typical from atypical bacteria., Methods: Design-observational, multi-center, prospective cohort study was conducted in 2 phases. Settings: 24 secondary and tertiary hospitals in Spain. Patients-A total of 495 consecutive hospitalized children between 1 month and 16 years of age with CAP were enrolled. Interventions-A score with 2 sequential steps was built (training set, 70% patients, and validation set 30%). Step 1 differentiates between viral and bacterial CAP and step 2 between typical and atypical bacterial CAP. Optimal cutoff points were selected to maximize specificity setting a high sensitivity (80%). Weights of each variable were calculated with a multivariable logistic regression. Main outcome measures-Viral or bacterial etiology., Results: In total, 262 (53%) children (median age: 2 years, 52.3% male) had an etiologic diagnosis. In step 1, bacterial CAPs were classified with a sensitivity = 97%, a specificity = 48%, and a ROC's area under the curve = 0.81. If a patient with CAP was classified as bacterial, he/she was assessed with step 2. Typical bacteria were classified with a sensitivity = 100%, a specificity = 64% and area under the curve = 0.90. We implemented the score into a mobile app named Pneumonia Etiology Predictor, freely available at usual app stores, that provides the probability of each etiology., Conclusions: This 2-steps tool can facilitate the physician's decision to prescribe antibiotics without compromising patient safety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To describe the etiology of community-acquired pneumonia (CAP) in hospitalized children in Spain and analyze the predictors of the etiology., Hypothesis: The different etiological groups of pediatric CAP are associated with different clinical, radiographic, and analytical data., Design: Observational, multicenter, and prospective study., Patient Selection: This study included children aged 1 month to 17 years with CAP, who were hospitalized between April 2012 and May 2019., Methods: An extensive microbiological workup was performed. The clinical, radiographic, and analytical parameters were analyzed for three etiological groups., Results: Among the 495 children included, at least one causative pathogen was identified in 262 (52.9%): pathogenic viruses in 155/262 (59.2%); atypical bacteria (AB), mainly Mycoplasma pneumonia, in 84/262 (32.1%); and typical bacteria (TyB) in 40/262 (15.3%). Consolidation was observed in 89/138 (64.5%) patients with viral CAP, 74/84 (88.1%) with CAP caused by AB, and 40/40 (100%) with CAP caused by TyB. Para-pneumonic pleural effusion (PPE) was observed in 112/495 (22.6%) patients, of which 61/112 (54.5%) presented a likely causative pathogen: viruses in 12/61 (19.7%); AB in 23/61 (37.7%); and TyB in 26/61 (42.6%). Viral etiology was significantly frequent in young patients and in those with low oxygen saturation, wheezing, no consolidation, and high lymphocyte counts. CAP patients with AB as the etiological agent had a significantly longer and less serious course as compared to those with other causative pathogens., Conclusions: Viruses and M. pneumoniae are the main causes of pediatric CAP in Spain. Wheezing, young age, and no consolidation on radiographs are indicative of viral etiology. Viruses and AB can also cause PPE. Since only a few cases can be directly attributed to TyB, the indications for antibiotics must be carefully considered in each patient., (© 2021 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Knowledge of thrombosis in children with SARS-CoV-2 is scarce. In this multicentre national cohort of children with SARS-CoV-2 involving 49 hospitals, 4 patients out of 537 infected children developed a thrombotic complication (prevalence of 0.7% (95% CI: 0.2% to 1.9%) out of the global cohort and 1.1% (95% CI: 0.3% to 2.8%) out of the hospitalised patients). We describe their characteristics and review other published paediatric cases. Three out of the four patients were adolescent girls, and only two cases had significant thrombotic risk factors. In this paediatric cohort, D-dimer value was not specific enough to predict thrombotic complications. Adolescence and previous thrombotic risk factors may be considered when initiating anticoagulant prophylaxis on children with SARS-CoV-2 disease (COVID-19)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Influenza is a generally a benign disease, but occasionally it can cause serious complications. There is controversy about the benefits of antiviral treatment., Objectives: To provide some recommendations on the treatment with oseltamivir in paediatric patients with influenza, based on the best data available and valid in our environment., Methods: The Respiratory Infections Group of the Spanish Society of Paediatric Infectious Diseases carried out a review of the literature. The findings were analysed using the GRADE methodology, and recommendations were made., Results: The systematic use of diagnostic tests for influenza in the outpatient setting, or in the emergency room, in immunocompetent patients with a compatible clinical picture is not recommended. If the aim is to prevent serious events, the use of antivirals is not recommended for the vast majority of healthy and asthmatic patients with influenza or suspected seasonal flu. The systematic use of oseltamivir in patients admitted to hospital with influenza is not recommended. Oseltamivir treatment is recommended in any patients with influenza and pneumonia or severe illness, and critically ill patients, especially during the first 48hours of illness. The treatment of patients with risk factors is recommended, considering their underlying disease. Influenza vaccination, together with basic isolation measures, continue to be the main tool in the prevention of influenza., Conclusion: In some situations, there are sufficient data to issue clear recommendations. In other situations, the data are incomplete, and only allows weak recommendations., (Copyright © 2019 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Using the data from the HERACLES clinical surveillance study (2007-2016), we describe the population impact of the 13-valent pneumococcal conjugate vaccine (PVC13) on invasive pneumococcal disease (IPD) in children <15 years of age in the Community of Madrid, Spain. After six years of the inclusion of PCV13 in the vaccination calendar (2010-2016), and despite changes in the Regional Immunization Programme that limited its availability, the net benefit incidence rate (IR) of IPD fell by 70.1% (IRR 0.3 [95% CI: 0.22-0.4]; p ≤ 0.001), mainly due to a significant reduction (91%) in the PCV13 serotypes (IRR 0.09 [95% CI: 0.05-0.16], p ≤ 0.001). Furthermore, no significant changes were detected in the IR of IPD caused by non-PCV13 serotypes. The IRs of the aggressive, resistant and most prevalent serotype in the analysed population, the 19A serotype, dramatically decreased from the beginning to the end of the study (98%) [IRR 0.03 (95% CI: 0.00-0.19), p ≤ 0.001], to its almost total disappearance. Remarkably, this reduction led to a pronounced decline in the percentage of cefotaxime-resistant isolates and the incidence of meningitis cases. Assessment of the clinical impact revealed a reduction in the number of all clinical presentations of IPD, confirming the effectiveness of the PCV13. Finally, PCV13 detected by PCR is predicted to have a stronger impact than the one based on culture methods, which can overlook more than 20% of cases of IPD, mainly pleural empyemas., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Hyponatremia (HN) < 135 mmol/L is a frequent finding in children with community-acquired pneumonia (CAP). We aimed to determine the proportion of syndrome of inappropriate antidiuretic hormone secretion (SIADH) among patients with CAP and HN. Moreover, we wished to investigate the relationship between HN and inflammatory markers, bacterial etiology and prognosis in hospitalized children with CAP., Methods: We carried out a prospective, observational, multicentre, prospective cohort study. Eligible participants were children from 1 month to 17 years old hospitalized due to CAP from 2012 to 2015., Results: A total of 150 children were analyzed. Forty-five (30%) patients had serum sodium levels of less than 135 mmol/L. Patients with HN had significantly higher concentrations of inflammatory biomarkers. They also had significantly lower osmolality and urine sodium. They also had longer hospitalizations and more days of fever. Only 16 out of the 45 (35%) patients with HN had confirmed calculated plasma osmolality (<275 mOsm/kg). Only 5 out of 37 (13%) patients with available measurements of plasma osmolality and urine sodium fulfilled the criteria for SIADH. Among the 16 patients with HN and hypo-osmolality, 15 had a fractional sodium excretion (EFNa) levels of less than 1%. We found a significant inverse linear correlation between serum sodium and C-reactive protein, as well as serum sodium and procalcitonin. We found a significant direct correlation between serum sodium and urine sodium., Conclusion: HN is a common finding in hospitalized children with CAP. True SIADH is a rare event. HN has a good correlation with inflammatory biomarkers.

Objectives: To evaluate the impact of 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in children., Methods: Children younger than 15years of age attending 27 hospitals in the Region of Madrid with confirmed pneumococcal meningitis were identified in a prospective surveillance study, from 2007 to 2015. Clinical data, neurological sequelae, pneumococcal vaccination status, serotyping and antibiotic susceptibility were recorded., Results: One hundred and four cases of pneumococcal meningitis were identified, 63 during the period of routine 7-valent pneumococcal conjugate vaccine immunisation (May 2007-April 2010) and 41 during the period of 13-valent pneumococcal conjugate vaccine immunisation (May 2010-April 2015). When both periods were compared, a 62% (95% CI: 45-75%) decrease in the incidence of pneumococcal meningitis was observed, from 2.19 cases per 100,000 inhabitants in the PCV7 period to 0.81 per 100,000 inhabitants in the PCV13 period (p=0.0001), mainly due to an 83% (95% CI: 30-96%) reduction in cases caused by serotype 19A. Isolates not susceptible to cefotaxime (MIC>0.5μg/L) decreased from 27% to 8%, (p=0.02). Mean patient ages rose from 28.7months to 38.5months (p<0.05). Case fatality rate across both periods was 5%. An unfavourable outcome (death or neurological sequelae) occurred in 27% of patients, while the rate was similar in both periods. There was no increase in meningitis caused by pneumococcal serotypes not included in 13-valent pneumococcal conjugate vaccine throughout the years of the study., Conclusions: Immunisation with 13-valent pneumococcal conjugate vaccine has reduced the rate of pneumococcal meningitis in children less than 15years, with a near-elimination of cefotaxime-resistant isolates, but morbidity has remained unchanged. A shift of pneumococcal meningitis towards slightly higher age groups was also observed., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To assess whether dexamethasone (DXM) decreases the time to recovery in patients with parapneumonic pleural effusion., Study Design: This was a multicenter, randomized, double blind, parallel-group, placebo-controlled clinical trial of 60 children, ranging in age from 1 month to 14 years, with community-acquired pneumonia (CAP) and pleural effusion. Patients received either intravenous DXM (0.25?mg/kg/dose) or placebo every 6 hours over a period of 48 hours, along with antibiotics. The primary endpoint was the time to recovery in hours, defined objectively. We also evaluated complications and adverse events., Results: Among the 60 randomized patients (mean age, 4.7 years; 58% female), 57 (95%) completed the study. Compared with placebo recipients, the patients receiving DXM had a shorter time to recovery, after adjustment by severity group and stratification by center (hazard ratio, 1.95; 95% CI, 1.10-3.45; P?=?.021). The median time to recovery for patients receiving DXM was 68 hours (2.8 days) shorter than patients receiving placebo (109 hours vs 177 hours; P?=?.037). In exploratory subgroup analysis, the median time to recovery for patients with simple effusion receiving DXM was 76 hours (3.1 days) shorter than for patients with simple effusion receiving placebo (P?=?.017). The median time to recovery for patients with complicated effusion receiving DXM was 14 hours (0.5 days) shorter than for patients with complicated effusion receiving placebo (P?=?.66). The difference in the effect of DXM in the 2 severity groups was not statistically significant (P?=?.138 for interaction). There were no significant differences in complications or adverse events attributable to the study drugs, except for hyperglycemia., Conclusion: In this trial, DXM seemed to be a safe and effective adjunctive therapy for parapneumonic pleural effusion., Trial Registration: ClinicalTrials.gov: NCT01261546., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In the Community of Madrid, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced the 7-valent (PCV7) in the fully government-funded Regional Immunization Program (RIP) in May, 2010, but was later excluded in May, 2012, and included again in January, 2015. These unique changes allowed us to assess the impact of the different pneumococcal vaccination policies on PCV13 uptake in infants and on the incidence rate (IR) of invasive pneumococcal disease (IPD) in children <15 years old. In this prospective, active, surveillance study, we estimated PCV13 uptakes, IR and incidence rate ratios (IRR) for total IPD and for IPD caused by PCV13- and non-PCV13 serotypes in children <15 years, stratified by age, in four periods with different vaccination policies: fully government-funded PCV7 vaccination, fully government-funded PCV13, mixed public/private funding and only private funding. Vaccine uptakes reached 95% in periods with public-funded pneumococcal vaccination, but fell to 67% in the private funding period. Overall, IR of IPD decreased by 68% (p<0.001) in 2014-15, due to 93% reduction in the IR of PCV13-type IPD (p<0.001) without significant changes in non-PCV13-type IPD. A fully government-funded PCV13 vaccination program lead to high vaccine uptake and dramatic reductions in both overall and PCV13-type IPD IR. When this program was switched to private PCV13 vaccination, there was a fall in vaccine coverage and stagnation in the decline of PCV13-type IPD with data suggesting a weakening of herd immunity.

Background: In the Region of Madrid, universal immunization with the 13-serotypes pneumococcal conjugate vaccine (PCV13) started in May 2010. In July 2012, public funding ceased. Vaccination coverage decreased from >95% to 82% in 2013 and to 67% in 2014. Our aim was to investigate the impact of PCV13 withdrawal from Madrid Region universal immunization program on the incidence of complicated pneumococcal bacteremia., Methods: We performed a multicenter retrospective cohort study, from 2009 to 2014. Participants were children aged <14 years with Streptococcus pneumoniae bacteremia. Complications were defined as any condition requiring intensive care or surgery. Sequelae were conditions lasting ≥90 days., Results: A total of 168 patients were recruited. One-fourth of both immunized and nonimmunized patients had complications. Global complications increased after PCV13 withdrawal. About 28% of PCV13 serotypes presented complications. Complications caused by PCV13 serotypes did not increase after July 2012. Non-PCV13 serotypes increased progressively from 2009 on, and 23% presented complications. A significant risk of complications was found for patients with meningitis, empyema, C-reactive protein >100 mg/L and serotype 1. A multivariate analysis indicated that complications were associated with meningitis and hospital admission after July 2012. Sequelae were significantly associated with children <2 years of age, meningitis and non-PCV13 serotypes., Conclusions: The incidence of complications caused by PCV13 serotypes did not increase 2 years after PCV13 withdrawal. Nevertheless, all-serotypes complications increased. The likely cause was that non-PCV13 serotypes (associated with meningitis) are on the rise.

Objective: To compare the incidence and epidemiology of bacteremic community-acquired pneumonia (CAP) in the setting of changes in 13-valent pneumococcal conjugate vaccine (PCV13) coverage., Study Design: In the region of Madrid, universal immunization with the PCV13 started in May 2010. In July 2012, public funding ceased. Vaccination coverage decreased from >95% to 82% in 2013 and to 67% in 2014. We performed a multicenter surveillance and case-control study from 2009-2014. Cases were hospitalized children with bacteremic CAP. Controls were children selected 1:1 from next-admitted with negative blood cultures and typical, presumed bacterial CAP., Results: Annual incidence of bacteremic CAP declined from 7.9/100,000 children (95% CI 5.1-11.1) in 2009 to 2.1/100,000 children (95% CI 1.1-4.1) in 2012. In 2014, 2 years after PCV13 was withdrawn from the universal vaccination program, the incidence of bacteremic CAP increased to 5.4/100,000 children (95% CI 3.5-8.4). We enrolled 113 cases and 113 controls. Streptococcus pneumoniae caused most of bloodstream infections (78%). Empyema was associated with bacteremia (P = .003, OR 3.6; 95% CI 1.4-8.9). Simple parapneumonic effusion was not associated with bacteremia. Incomplete PCV immunization was not a risk factor for bacteremic pneumonia., Conclusions: High rate of PCV13 immunization was associated with decreased incidence of bacteremic CAP; this incidence increased when rate of immunization fell. Empyema (but not parapneumonic pleural effusion) was associated with bacteremia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Acquired hemophagocytic lymphohistiocitosis (HLH) syndrome can be a complication of visceral leishmaniasis (VL). A multicenter prospective study was conducted to determine the frequency of HLH syndrome in children with VL. Twenty-four children with VL were identified, and 10 (41%) developed HLH syndrome. VL should be ruled out in all children with HLH criteria living in or coming from endemic areas.

In Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13 serotypes.

Aim: To determine whether the treatment with oseltamivir improves the outcome of children with confirmed influenza infection and no other underlying disease., Methods: Multicentric, retrospective study performed in 10 hospitals of Madrid between September 2010 and June 2012. All children admitted to the hospitals with confirmed influenza infections were eligible. Children with risk factors for serious disease and nosocomial influenza infections were excluded. Asthma was not considered an exclusion factor. The study compared patients treated and untreated with oseltamivir. Fever duration, oxygen support, antibiotics administration, length of hospital stay, intensive care admission and bacterial complications were analyzed. To compare variables, χ(2) test, Fisher exact test, ANOVA or Mann-Whitney U test were used., Results: Two hundred eighty-seven children were included and 93 of them were treated with oseltamivir (32%). There were no significant differences between treated and untreated patients in days of fever after admission (1.7 ± 2; 2.1 ± 2.9, P > 0.05), length of stay (5.2 ± 3.6; 5.5 ± 3.4, P > 0.05), days of hypoxia (1.6 ± 2.3; 2.1 ± 2.9, P > 0.05), diagnosis of bacterial pneumonia (10%; 17%, P > 0.05), intensive care admission (6.5%; 1.5%,P > 0.05) or antibiotic prescription (44%; 51%, P > 0.05). There were no differences when the population was stratified by age (below or over 1 year) or by the presence or absence of asthma., Conclusions: There were no proven benefits of treatment with oseltamivir in hospitalized pediatric patients without the underlying diseases or risk factors for developing a serious illness, including those with asthma.

Background: Differences in invasive pneumococcal disease (IPD) in children are expected after a change from 7-valent pneumococcal conjugate vaccine (PCV7) to 13-valent pneumococcal conjugate vaccine (PCV13). Universal vaccination with PCV7 started in Madrid in November 2006, and it switched to PCV13 in June 2010., Methods: A prospective, laboratory-confirmed (by culture or polymerase chain reaction), clinical surveillance including all pediatric IPD requiring hospitalization in Madrid was performed in all hospitals with a pediatric department and included four 1-year periods from May 2007 to April 2011. Incidence rate (IR) was calculated as number cases per 100,000 inhabitants using children population data., Results: Six hundred fourteen IPDs were identified: 209 parapneumonic pneumococcal empyema, 191 bacteremic pneumonia, 75 primary bacteremia, 72 meningitis, 38 IPDs secondary to otic foci and 29 others. The incidence of IPD remained unchanged during 2007-2010 (IR=≈17.0), with a marked decrease in 2010-2011 (IR=11.34; P<0.05) attributable to reduction in children younger than 24 months (50.19 in 2008-2009 compared with 24.92 in 2010-2011; P<0.005). The incidence of bacteremic pneumonia (R²=0.966; β=1.132; P=0.017) and meningitis (R²=0.898; β=0.505; P=0.052) showed decreasing linear trends over time. The incidence of parapneumonic pneumococcal empyema increased in 2009-2010 but decreased in 2010-2011 (6.73 vs. 4.14; P=0.019). The incidence of IPDs by PCV13 serotypes was significantly (P≤0.004) lower in 2010-2011 (8.78) than in previous periods (IR=≈13.5)., Conclusions: Early data regarding changing from PCV7 to PCV13 use in the childhood vaccination calendar indicate that reductions in IR of bacteremic pneumonia and meningitis after PCV7 introduction (by reduction of cases by serotypes 1 and 19A) further decreased and there was a reversion of the increase in IR of parapneumonic pneumococcal empyema from 2010-2011, mainly because of reduction in serotype 1 and 19A cases.

Objective: To describe the epidemiological and clinical characteristics of children hospitalized with 2009 pandemic influenza (pH1N1) in Madrid, Spain., Patients/methods: We included patients less than 14 years of age admitted to one of 18 hospitals in Madrid, Spain, between May 1 and November 30, 2009 and diagnosed with pH1N1 by polymerase chain reaction. A retrospective chart review was conducted and data were compared by age, presence of high-risk medical conditions, and pediatric intensive care unit (PICU) admission., Results: A total of 517 pH1N1 cases were included for final analysis. One hundred and forty-two patients (27·5%) had predisposing underlying illnesses, with immunosuppression (36 children, 7%) and moderate persistent asthma (34, 6·6%) being the most common ones. Patients with underlying medical conditions had longer hospital stays [median 5, interquartile range (IQR) 3-8 days, versus median 4, IQR 3-6, P < 0·001] and required intensive care (20·4% versus 5·9%, P < 0·001) and mechanical ventilation more frequently than previously healthy children. Globally, intensive care was required for 51 patients (10%) and invasive mechanical ventilation for 12 (2%). Pediatric intensive care unit admission was significantly associated with abnormal initial chest X-ray [Odds Ratio (OR) 3·5, 95% confidence interval (CI) 1·5-8·5], underlying neurological condition (OR 3·1, CI 1·2-7·5) and immunosuppression (OR 2·9, 1·2-6·8). Five patients (0·9%) died; two with severe neurological disease, two with leukemia, and one with a malignant solid tumor., Conclusions: Children with underlying medical conditions experienced more severe pH1N1 disease. Risk factors for admission to the PICU included underlying neurological conditions, immunosuppression and abnormal initial chest X-ray., (© 2011 Blackwell Publishing Ltd.)

Candidemia is an important problem in pediatrics. In our hospital, highest candidemia rates were documented among children with congenital heart disease (CHD). A series was conducted to describe the clinical and mortality features of candidemia in these patients. Fifty-two cases (1988-2000) included very young infants (median age, 2 months) who received long-term antibiotic treatment (median, 20.5 days). Candida parapsilosis predominated (54%). Endovascular infections occurred in 11.5%. In-hospital mortality was 39% and related mortality 14%. Maintenance of catheter (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.0-37.2; P = .05) and severity of patients as measured with the Pediatric Risk Score of Mortality I (OR, 1.1, 95% CI, 1.0-1.3; P = .05) were independently associated with mortality. In summary, candidemia in children with CHD is diagnosed to very young infants with prolonged antibiotic therapy. Mortality is high but, in most cases, is not related to candidemia. Optimal management may include exclusion of endocarditis, early antifungal treatment, and catheter removal.

Objective: To identify the main risk factors for the acquisition of candidemia in children with congenital heart disease (CHD) in order to improve the clinical management of these patients., Design: A case-control study., Setting: A large tertiary-care referral center in Spain with a pediatric intensive care unit (PICU) to which more than 500 children with CHD are admitted annually., Patients: All patients had CHD and were admitted to the PICU during 1995-2000. Case patients were defined as patients with candidemia, and control patients were defined as patients without candidemia., Results: Twenty-eight case patients and 47 control subjects were included in the study. Case patients were younger (mean age [+/-SD], 12.5+/-32.0 vs 38.0+/-48.0 months; P<.01) and had a longer median PICU stay (19 vs 4 days; P<.01), and a greater percentage of case patients previously had Candida species isolated from specimens other than blood (eg, bronchial aspirates, urine, or skin specimens) (39% vs 4%; P<.01). Severity of clinical condition, as measured by the Therapeutic Intervention Scoring System (TISS) 1 week after PICU admission (odds ratio, 1.15; 95% confidence interval, 1.05-1.26; P<.01), and receipt of antibiotic treatment for more than 5 days (odds ratio, 13.42; 95% confidence interval, 1.31-137.13; P=.03) were independently associated with the development of candidemia., Conclusions: Patients with CHD who have a high TISS score 1 week after PICU admission and patients who have received prolonged antibiotic therapy should be considered at high risk for candidemia. Our results suggest that shorter courses of antibiotic therapy, routine surveillance culture for Candida species, and initiation of preemptive or empirical antifungal treatment could help in the clinical management of these patients.

Objective: To analyze the secular trends of candidemia in a large tertiary-care hospital to determine the overall incidence, as well as the incidence by ward and by species, and to detect the occurrence of outbreaks., Design: Retrospective descriptive analysis. Secular trends were calculated using the Mantel-Haenszel test., Setting: A large tertiary-care referral center in Spain with a pediatric intensive care unit (ICU) to which more than 500 children with congenital cardiac disease are admitted annually., Patients: All patients with candidemia occurring from 1988 to 2000 were included. Cases were identified from laboratory records of blood cultures., Results: There were 331 episodes of candidemia. The overall incidence of nosocomial candidemia was 0.6 episode per 1,000 admissions and remained stable throughout the study period (P = .925). The species most frequently isolated was Candida albicans, but the incidence of C. parapsilosis candidemia increased (P = .035). In the pediatric ICU, the incidence of C. parapsilosis was 5.6 episodes per 1,000 admissions and it was the predominant species. Outbreaks occurred occasionally in the pediatric ICU, suggesting nosocomial transmission., Conclusions: During this 13-year period, the incidence of candidemia remained stable in this hospital, but C. parapsilosis increased in frequency. Occasional outbreaks of candidemia suggested nosocomial transmission of Candida species.

Objective: To determine prognostic factors in child recipients of hematopoietic stem cell transplantation from blood or bone marrow (BMT) requiring critical care., Design: Retrospective study of a cohort of patients., Setting: Pediatric Intensive Care Unit (PICU) in a university tertiary care center., Patients and Participants: Child recipients of BMT requiring PICU admission., Measurements and Results: Of the 151 children receiving transplants in our institution, 44 (29.1%) had 49 admissions to the PICU. Mechanical ventilation (MV) was required in 34 patients (69.4% of all admissions). Overall mortality was 31/44 (70.4%). Mortality in patients requiring MV and not requiring MV was 26/34 (76.5%) and 5/10 (50%), respectively. The following variables were significantly associated with mortality in the univariate analysis: male gender (P=0.02), older age (P=0.03), acute graft versus host disease (aGVHD) grades III or IV (P=0.01), severe hemorrhagic cystitis (P=0.01), the diagnosis of lung injury (P=0.04), the need for MV (P=0.03) or for renal replacement therapy (P=0.02), the presence of respiratory (P=0.003), cardiovascular (P=0.009) or gastrointestinal (P=0.01) failures, and the failure of > or =3 organs (P=0.01). In the multivariate analysis, the presence of aGVHD grades III or IV, male gender, severe hemorrhagic cystitis, and the failure of > or =3 organs were found to be independent predictors of mortality., Conclusions: The need for intensive care is common among child recipients of a BMT. These patients have a high mortality rate but some complications are reversible with critical care support. Certain clinical parameters are useful to establish a realistic prognosis and to optimize the use of the available resources.

Background: A preoperative and postoperative chemotherapy regimen was applied to nonmetastatic osteosarcoma of the extremities in patients under 16 years of age to prevent the progress to metastatic disease and reduce the volume of the primary tumor in order to assess a conservative surgery., Patients and Methods: A modified T-10 chemotherapy regimen was used before surgery, including high dose methotrexate, vincristine, bleomycin, cyclophosphamide and dactinomycin. After surgery patients with a grade of tumor necrosis > 90% received the same regimen up to 45 weeks of treatment. For the cases with necrosis < 90%, this regimen was substituted by adriamycin and cisplatinum. Survival was studied in relation with age, sex, tumor site, levels of alkaline phosphatase and LDH, surgical treatment and tumor necrosis in the surgical specimen after preoperative chemotherapy. Uni and multivariate analysis were performed., Results: Twenty seven patients with ages ranging from 5 to 15 years (median 11 years) were treated. The most common site of primary tumor was femur, followed by humerus and tibia. In 9 cases (33%) tumor necrosis was > 90%. Consecutive surgery was performed in 20 patients and 7 suffered amputation or disarticulation of the extremity. Twenty patients remain alive and disease-free at a median follow-up of 84 months. The probability of disease-free survival at 50 months is 71%. The only factor which influenced significantly the survival was the grade of tumor necrosis. Survival was 100% for the 9 patients with necrosis > 90% and 53% for the 18 cases with necrosis > 90% (p = 0.022)., Conclusions: Preoperative and postoperative chemotherapy achieve disease-free survival in more than two thirds of patients with nonmetastatic osteosarcoma of the extremities and allow a non mutilating surgical treatment in the majority of them.

Background: Lymphocyte subset reconstitution was studied in 65 patients undergoing allogeneic and autologus bone marrow transplantation (BMT)., Patients and Methods: The expression of molecules on the membrane of lymphocyte subsets was assessed by two-colour flow cytometry and a direct immunofluorescence assay. The functional capacity of the patient's T lymphocytes following transplantation was identified by stimulation whit peripheral blood lymphocytes; B cells from BMT recipients were tested for their ability to respond, in vitro, to pokeweed (PWD) mitogen., Results: 1) The proportion of CD8+ T lymphocytes was higher than the CD4+ T lymphocytes until 1 1/2 year after-BMT, with high percentage of immature T cells (CD3+, CD8+, HLA-DR+, CD25-) in the first nine months post-transplant. Moreover, a large proportion of T lymphocytes lacked CD5 expression in the first year following BMT. 2) T-cell proliferative response to PHA was low with subsequent recovery until normality. 3) Low numbers of B cells in the first two months with a significant increase since then until 1 1/2 year after-BMT; the phenotype of these B cells was mainly CD19+, CD5+. 4) High in vitro spontaneous immunoglobulin production by peripheral blood B lymphocytes and an impaired response to PWM was observed. 5) Increased percentage of cells with natural killer (CD56) cell phenotype was seen during the 2nd and 3rd months after the graft infusion. After 1 1/2 year postgrafting, this percentage returned to normal level., Conclusions: Taken together, these data indicate the existence of numerous abnormalities in several subsets of peripheral blood lymphocytes after BMT and suggest a slow kinetics of immune recovery after human marrow transplantation being complete between 18 and 24 months following BMT.

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise. We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males. The mean age of the patients at the time of the study was 18.2 +/- 3.6 years (range 13.8-29.0), and when given chemotherapy treatment was 10.2 +/- 3.0 years (range 6-16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0-16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted.

The use of recombinant human granulocyte-stimulating factor (G-CSF) has been shown to effectively accelerate granulocytic recovery after autologous bone marrow transplantation (BMT) in adults. The experience, however, is limited in children. We evaluated the hematopoietic reconstitution in 41 consecutive children undergoing autologous BMT for hematologic malignancies (21 acute lymphoblastic leukemia, five non-Hodgkin's lymphoma) and solid tumours (seven neuroblastoma, two brain tumor, three Ewing's sarcoma, two Wilms' tumor, one rhabdomyosarcoma). Their ages ranged from 2 to 16 years (mean 7.2 years). rhG-CSF was given at a dose of 10 micrograms/kg/day i.v. in a 2h infusion from day +1 until +28 or until the absolute neutrophil count (ANC) was > 1 x 10(9)/L. These patients were compared with a similar historical control group of 38 children who did not receive rhG-CSF after autologous BMT. The number of cells infused was similar in both groups. At the dose and schedule used in the present study, rhG-CSF was well tolerated and no side-effects were observed. The number of cell infused was similar in both groups. At the dose and schedule used in the present study, rhG-CSF was well tolerated and no side-effects were observed. Our data show that rhG-CSF accelerates engraftment and reduces the number of febrile days and antibiotic use. Furthermore, patients who were treated had less infections.