José María Martinón-Sánchez

Nasal continuous positive airway pressure with heliox versus air oxygen in infants with acute bronchiolitis: a crossover study.

OBJECTIVE. The purpose of this work was to evaluate the effects of administering either heliox or air oxygen in combination with nasal continuous positive airway pressure in infants with refractory bronchiolitis. PATIENT AND METHODS. We conducted a prospective, interventional, single-center, crossover study in a teaching hospital including infants 1 month to 2 years of age, consecutively admitted to the PICU from February 2004 to February 2005 for treatment of severe acute bronchiolitis unresponsive to therapy. Patients with a clinical score (Modified Woods Clinical Asthma Score) of >5, arterial oxygen saturation of <92%, or transcutaneous CO2 pressure of >50 mmHg despite supportive therapy, nebulized L-epinephrine, and heliox therapy through a nonrebreathing reservoir face mask were eligible. During the study period, 40 infants with bronchiolitis were admitted to the PICU; 12 fulfilled inclusion criteria. A predetermined balanced sequential allocation to either 30 minutes of treatment with nasal continuous positive airway pressure with heliox or to air-oxygen nasal continuous positive airway pressure was performed. Measurements were taken at baseline and after 30 minutes of each treatment. RESULTS. Baseline mean values were as follows: nasal continuous positive airway pressure of 7.2 cmH2O; clinical score of 7.7 points; transcutaneous CO2 pressure of 61.6 mmHg; and arterial oxygen saturation of 88.6%, with the fraction of inspired oxygen at 35.4%. Clinical score, transcutaneous CO2 pressure, and arterial oxygen saturation improved during the study time with both heliox-nasal continuous positive airway pressure and air-oxygen-nasal continuous positive airway pressure: after 1 hour, the clinical score fell 1.7 points, transcutaneous CO2 pressure decreased 8.2 mmHg, and arterial oxygen saturation increased by 7.7%. Improvement in clinical score was double with heliox-nasal continuous positive airway pressure compared with the air-oxygen-nasal continuous positive airway pressure (2.12 vs 1.08 points), and the fall in the transcutaneous CO2 pressure was greater with heliox-nasal continuous positive airway pressure compared with air-oxygen-nasal continuous positive airway pressure (9.7 vs 5.4 mm Hg). There was no difference in arterial oxygen saturation between groups. No patients required endotracheal intubation. No adverse effects attributable to either of the study interventions were detected. CONCLUSIONS. Nasal continuous positive airway pressure improves the clinical score and the CO2 elimination of infants with refractory bronchiolitis. These positive effects are significantly enhanced when nasal continuous positive airway pressure is combined with heliox instead of air oxygen. Both techniques are noninvasive, seem safe, and may reduce the need for endotracheal intubation.

Viral Co-Infections in Pediatric Patients Hospitalized with Lower Tract Acute Respiratory Infections.

Background Molecular techniques can often reveal a broader range of pathogens in respiratory infections. We aim to investigate the prevalence and age pattern of viral co-infection in children hospitalized with lower tract acute respiratory infection (LT-ARI), using molecular techniques. Methods A nested polymerase chain reaction approach was used to detect Influenza (A, B), metapneumovirus, respiratory syncytial virus (RSV), parainfluenza (1–4), rhinovirus, adenovirus (A—F), bocavirus and coronaviruses (NL63, 229E, OC43) in respiratory samples of children with acute respiratory infection prospectively admitted to any of the GENDRES network hospitals between 2011–2013. The results were corroborated in an independent cohort collected in the UK. Results A total of 204 and 97 nasopharyngeal samples were collected in the GENDRES and UK cohorts, respectively. In both cohorts, RSV was the most frequent pathogen (52.9% and 36.1% of the cohorts, respectively). Co-infection with multiple viruses was found in 92 samples (45.1%) and 29 samples (29.9%), respectively; this was most frequent in the 12–24 months age group. The most frequently observed co-infection patterns were RSV—Rhinovirus (23 patients, 11.3%, GENDRES cohort) and RSV—bocavirus / bocavirus—influenza (5 patients, 5.2%, UK cohort). Conclusion The presence of more than one virus in pediatric patients admitted to hospital with LT-ARI is very frequent and seems to peak at 12–24 months of age. The clinical significance of these findings is unclear but should warrant further analysis.

Does Viral Co-Infection Influence the Severity of Acute Respiratory Infection in Children?

Background Multiple viruses are often detected in children with respiratory infection but the significance of co-infection in pathogenesis, severity and outcome is unclear. Objectives To correlate the presence of viral co-infection with clinical phenotype in children admitted with acute respiratory infections (ARI). Methods We collected detailed clinical information on severity for children admitted with ARI as part of a Spanish prospective multicenter study (GENDRES network) between 2011–2013. A nested polymerase chain reaction (PCR) approach was used to detect respiratory viruses in respiratory secretions. Findings were compared to an independent cohort collected in the UK. Results 204 children were recruited in the main cohort and 97 in the replication cohort. The number of detected viruses did not correlate with any markers of severity. However, bacterial superinfection was associated with increased severity (OR: 4.356; P-value = 0.005), PICU admission (OR: 3.342; P-value = 0.006), higher clinical score (1.988; P-value = 0.002) respiratory support requirement (OR: 7.484; P-value < 0.001) and longer hospital length of stay (OR: 1.468; P-value < 0.001). In addition, pneumococcal vaccination was found to be a protective factor in terms of degree of respiratory distress (OR: 2.917; P-value = 0.035), PICU admission (OR: 0.301; P-value = 0.011), lower clinical score (-1.499; P-value = 0.021) respiratory support requirement (OR: 0.324; P-value = 0.016) and oxygen necessity (OR: 0.328; P-value = 0.001). All these findings were replicated in the UK cohort. Conclusion The presence of more than one virus in hospitalized children with ARI is very frequent but it does not seem to have a major clinical impact in terms of severity. However bacterial superinfection increases the severity of the disease course. On the contrary, pneumococcal vaccination plays a protective role.

Cerebral syncope in children

We report a child with recurrent syncopal episodes who underwent head-up tilt testing according to a protocol that includes continuous and noninvasive measurement of brain oxygen saturation. We demonstrated significant cerebral hypoxemia during syncope without concomitant systemic hemodynamic disturbances. This response to head-up tilt test suggested the diagnosis of cerebral syncope.

Impact of Rotavirus Vaccination on Childhood Hospitalization for Seizures.

Background: Rotavirus vaccine (RV) might reduce the risk of hospitalization due to childhood seizures (CS). We aimed to identify and assess variations in the incidence of hospitalizations for CS among children <5 years of age before and after RV introduction. Methods: Annual hospitalization rates for any kind of CS, before and after RV introduction in 2007, were calculated using the official surveillance system for hospitalization data. Results: Our study cohort totaled 6149 children <5 years of age admitted to the hospital between 2003 and 2013 with any kind of CS (780.3* + 779.0* + 333.2* + 345* ICD-9-CM code). The annual hospitalization rates for any kind of CS in children <5 years of age were correlated with RV coverage (r = −0.673; P = 0.033) and rotavirus acute gastroenteritis admission rates (&rgr; = 0.506; P = 0.001), with decrease rates ranging from 16.2% (95% confidence interval: 8.3–23.5%) in 2007 to 34.0% (27.3–40.1%) in 2010, as compared with the median rate of the pre-vaccination period (2003 to 2006). Similarly, for convulsions (780.3*ICD-9-CM code), the decrease seen in children <5 years of age was significantly correlated with the increase in RV coverage (r = −0.747; P = 0.013) and rotavirus acute gastroenteritis admission rates (&rgr; = 0.543; P < 0.001), with decrease rates ranging from 18.7% (9.6–26.8%) in 2007 to 42.5% (35.3–48.9%) in 2012. Significant results were also obtained for infants <12 months and infants 1–2 years of age. In the remaining age groups or diagnostic categories analyzed, changes were either not significant or not related to vaccination changes or rotavirus acute gastroenteritis admission rates. Conclusions: Our results show that rotavirus vaccination may have a significant impact in the decrease in seizure-related hospitalizations in childhood. This additional benefit of rotavirus vaccination seems more marked in the youngest infants.

An estimation of indirect costs caused by acute rotavirus gastroenteritis in a Galician area, Spain

Despite the fact that rotavirus gastroenteritis is currently considered to be the most common pediatric disease in the European Community, preventable by vaccination, specific data about the indirect economic burden generated by rotavirus in Europe are limited [9]. In Spain, economic data on rotavirus are even more limited, and its impact in terms of indirect costs is unknown [2–4]. We have tried to assess the indirect economic burden of acute gastroenteritis induced by rotavirus in infants from a Galician area (Northwest of Spain), and to compare it with the burden due to acute gastroenteritis from other causes. For this purpose, a prospective, observational study was conducted from December 2005 through April 2006 in a pediatric continued care center, involving 88 infants under 2 years of age with acute gastroenteritis, in which all nonmedical expenses from the start to the end of the diseases were recorded in detail using personal interviews and telephone contacts. Moreover, fecal tests were performed in all the patients. All expenses incurred before, during, and after patient contact and study entry, from symptom start to total recovery of the child, were recorded. Expenses during care or hospitalization in terms of diets, materials, or medication were considered as part of direct (hospital) costs, and were not counted as indirect expenses. Priority was always given to the “exact” cost, when known by the parents. Costs in the following areas were evaluated and calculated as specified:

Clitoris and labia minora agenesis – an undescribed malformation

To the Editor: Although exceptionally rare, congenital external genitalia hypoplasia has been previously described, mainly as a part of complex syndromes (1). After reviewing the literature, we have not found any reference to congenital lack of labia minora or combination of clitoris and labia minora agenesis without further associated anomalies (2–5). Three girls with isolated external genitalia anomalies consisting of clitoral agenesis and lack of one or both labia minora are reported:

Development and Validation of a New Clinical Scale for Infants with Acute Respiratory Infection: The ReSVinet Scale.

Background and Aims A properly validated scoring system allowing objective categorization of infants with acute respiratory infections (ARIs), avoiding the need for in-person assessment and that could also be used by non-health professionals is currently not available. We aimed to develop a new clinical assessment scale meeting these specifications. Methods We designed a clinical scale (ReSVinet scale) based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points.170 children under two years of age with ARI were assessed independently by three pediatricians using this scale. Parents also evaluated their offspring with an adapted version of the scale in a subset of 61 cases. The scale was tested for internal consistency (Cronbach’s alpha), Pearson correlation coefficient for the items in the scale, inter-observer reliability (kappa index) and floor-ceiling effect. Results Internal consistency was good for all the observers, with the lowest Cronbach’s alpha being 0.72. There was a strong correlation between the investigators (r-value ranged 0.76–0.83) and also between the results obtained by the parents and the investigators(r = 0.73). Light’s kappa for the observations of the three investigators was 0.74. Weighted kappa in the group evaluated by the parents was 0.73. The final score was correlated with length of hospital stay, PICU admission and Wood-Downes Score. Conclusions The ReSVinet scale may be useful and reliable in the evaluation of infants with ARI, particularly acute bronchiolitis, even with data obtained from medical records and when employed by parents. Although further studies are necessary, ReSVinet scale already complies with more score validation criteria than the vast majority of the alternatives currently available and used in the clinical practice.

Bacteremia in Children Hospitalized with Respiratory Syncytial Virus Infection

Background The risk of bacteremia is considered low in children with acute bronchiolitis. However the rate of occult bacteremia in infants with RSV infection is not well established. The aim was to determine the actual rate and predictive factors of bacteremia in children admitted to hospital due to confirmed RSV acute respiratory illness (ARI), using both conventional culture and molecular techniques. Methods A prospective multicenter study (GENDRES-network) was conducted between 2011–2013 in children under the age of two admitted to hospital because of an ARI. Among those RSV-positive, bacterial presence in blood was assessed using PCR for Meningococcus, Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus, in addition to conventional cultures. Results 66 children with positive RSV respiratory illness were included. In 10.6% patients, bacterial presence was detected: H. influenzae (n = 4) and S. pneumoniae (n = 2). In those patients with bacteremia, there was a previous suspicion of bacterial superinfection and had received empirical antibiotic treatment 6 out of 7 (85.7%) patients. There were significant differences in terms of severity between children with positive bacterial PCR and those with negative results: PICU admission (100% vs. 50%, P-value = 0.015); respiratory support necessity (100% vs. 18.6%, P-value < 0.001); Wood-Downes score (mean = 8.7 vs. 4.8 points, P-value < 0.001); GENVIP scale (mean = 17 vs. 10.1, P-value < 0.001); and length of hospitalization (mean = 12.1 vs. 7.5 days, P-value = 0.007). Conclusion Bacteremia is not frequent in infants hospitalized with RSV respiratory infection, however, it should be considered in the most severe cases.

Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10−8) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52–0.73; P-value = 9.62 × 10−9). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55–0.76, P-value = 3.25 × 10−8). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.