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.     

Pediatric Drug Safety Surveillance in FDA-AERS: A Description of Adverse Events from GRiP Project

Individual case safety reports (ICSRs) are a cornerstone in drug safety surveillance. The knowledge on using these data specifically for children is limited. We studied characteristics of pediatric ICSRs reported to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Public available ICSRs reported in children (0–18 years) to FAERS were downloaded from the FDA-website for the period Jan 2004-Dec 2011. Characteristics of these ICSRs, including the reported drugs and events, were described and stratified by age-groups. We included 106,122 pediatric ICSRs (55% boys and 58% from United States) with a median of 1 drug [range 1–3] and 1 event [1–2] per ICSR. Mean age was 9.1 years. 90% was submitted through expedited (15-days) (65%) or periodic reporting (25%) and 10% by non-manufacturers. The proportion and type of pediatric ICSRs reported were relatively stable over time. Most commonly reported drug classes by decreasing frequency were ‘nervous system drugs’ (58%), ‘antineoplastics’ (32%) and ‘anti-infectives’ (25%). Most commonly reported system organ classes were ‘general’ (13%), ‘nervous system’ (12%) and ‘psychiatric’ (11%) disorders. Duration of use could be calculated for 19.7% of the reported drugs, of which 14.5% concerned drugs being used long-term (>6 months). Knowledge on the distribution of the drug classes and events within FAERS is a key first step in developing pediatric specific methods for drug safety surveillance. Because of several differences in terms of drugs and events among age-categories, drug safety signal detection analysis in children needs to be stratified by each age group.     

Clinical Characteristics Are Similar across Type A and B Influenza Virus Infections

Background

Studies that aimed at comparing the clinical presentation of influenza patients across virus types and subtypes/lineages found divergent results, but this was never investigated using data collected over several years in a countrywide, primary care practitioners-based influenza surveillance system.

Methods

The IBVD (Influenza B in Vircases Database) study collected information on signs and symptoms at disease onset from laboratory-confirmed influenza patients of any age who consulted a sentinel practitioner in France. We compared the clinical presentation of influenza patients across age groups (0–4, 5–14, 15–64 and 65+ years), virus types (A, B) and subtypes/lineages (A(H3N2), pandemic A(H1N1), B Victoria, B Yamagata).

Results

Overall, 14,423 influenza cases (23.9% of which were influenza B) were included between 2003–2004 and 2012–2013. Influenza A and B accounted for over 50% of total influenza cases during eight and two seasons, respectively. There were minor differences in the distribution of signs and symptoms across influenza virus types and subtypes/lineages. Compared to patients aged 0–4 years, those aged 5–14 years were more likely to have been infected with type B viruses (OR 2.15, 95% CI 1.87–2.47) while those aged 15–64 years were less likely (OR 0.83, 95% CI 0.73–0.96). Males and influenza patients diagnosed during the epidemic period were less likely to be infected with type B viruses.

Conclusions

Despite differences in age distribution, the clinical illness produced by the different influenza virus types and subtypes is indistinguishable among patients that consult a general practitioner for acute respiratory infections.     

Phenotypic and genotypic characteristics of mastocytosis according to the age of onset

Adult's mastocytosis is usually associated with persistent systemic involvement and c-kit 816 mutation, while pediatrics disease is mostly limited to the skin and often resolves spontaneously. We prospectively included 142 adult patients with histologically proven mastocytosis. We compared phenotypic and genotypic features of adults patients whose disease started during childhood (Group 1, n = 28) with those of patients whose disease started at adult's age (Group 2, n = 114). Genotypic analysis was performed on skin biopsy by sequencing of c-kit exons 17 and 8 to 13. According to WHO classification, the percentage of systemic disease was similar (75 vs. 73%) in 2 groups. C-kit 816 mutation was found in 42% and 77% of patients in groups 1 and 2, respectively (p<0.001). 816 c-kit mutation was associated with systemic mastocytosis in group 2 (87% of patients with systemic mastocytosis vs. 45% with cutaneous mastocytosis, p = 0.0001). Other c-kit activating mutations were found in 23% of patients with mastocytosis' onset before the age of 5, 0% between 6 and 15 years and 2% at adults' age (p<0.001). In conclusion, pathogenesis of mastocytosis significantly differs according to the age of disease's onset. Our data may have major therapeutic relevance when considering c-kit-targeted therapy.     

Circulating microRNAs and Outcome in Patients with Acute Heart Failure

Background

The biomarker value of circulating microRNAs (miRNAs) has been extensively addressed in patients with acute coronary syndrome. However, prognostic performances of miRNAs in patients with acute heart failure (AHF) has received less attention.

Methods

A test cohort of 294 patients with acute dyspnea (236 AHF and 58 non-AHF) and 44 patients with stable chronic heart failure (CHF), and an independent validation cohort of 711 AHF patients, were used. Admission levels of miR-1/-21/-23/-126/-423-5p were assessed in plasma samples.

Results

In the test cohort, admission levels of miR-1 were lower in AHF and stable CHF patients compared to non-AHF patients (p = 0.0016). Levels of miR-126 and miR-423-5p were lower in AHF and in non-AHF patients compared to stable CHF patients (both p<0.001). Interestingly, admission levels of miR-423-5p were lower in patients who were re-admitted to the hospital in the year following the index hospitalization compared to patients who were not (p = 0.0001). Adjusted odds ratio [95% confidence interval] for one-year readmission was 0.70 [0.53–0.93] for miR-423-5p (p = 0.01). In the validation cohort, admission levels of miR-423-5p predicted 1-year mortality with an adjusted odds ratio [95% confidence interval] of 0.54 [0.36–0.82], p = 0.004. Patients within the lowest quartile of miR-423-5p were at high risk of long-term mortality (p = 0.02).

Conclusions

In AHF patients, low circulating levels of miR-423-5p at presentation are associated with a poor long-term outcome. This study supports the value of miR-423-5p as a prognostic biomarker of AHF.     

Antiretroviral Therapy and Reasons for Not Taking It among Men Having Sex with Men (MSM)—Results from the European MSM Internet Survey (EMIS)

Background

The preventive effects of antiretroviral treatment (ART) on onward transmission of HIV are a major reason for broadening eligibility for ART. In the WHO European Region, surveillance reveals substantial differences in access to ART across regions and sub-populations. We analysed self-reported data on ART and reasons for not taking ART from EMIS, a large Pan-European Internet survey among men-who-have-sex-with-men (MSM).

Methods

Respondents from 38 European countries reported their last HIV test result and, if diagnosed with HIV, their treatment status, and reasons for not taking or having stopped ART from a 7 item multiple choice list and/ or answered an open-ended question to give other reasons. Responses were classified as fear of consequences, perceived lack of need, and ART inaccessibility based on factor analysis. Associations between not taking ART because of fear of consequences, and demographic, behavioural and contextual indicators were identified in a multivariable regression model.

Results

13,353 (7.7%) of 174,209 respondents had been diagnosed with HIV. Among them 3,391 (25.4%) had never received ART, and 278 (2.1%) had stopped taking ART. Perceived lack of need was by far the most common reason for not taking or stopping ART (mentioned by 3259 (88.8%) respondents), followed by fear of consequences (428 (11.7%)), and ART inaccessibility (86 (2.3%)). For all reasons, an East-West gradient could be seen, with larger proportions of men living in Central and Eastern Europe reporting reasons other than medical advice for not taking ART. A minority of men were reluctant to start ART independent of medical advice and this was associated with experiences of discrimination in health care systems.

Conclusions

ART is widely available for MSM diagnosed with HIV across Europe. Not being on treatment is predominantly due to treatment not being recommended by their physician and/or not perceived to be needed by the respondent.     

The Effectiveness of Inodilators in Reducing Short Term Mortality among Patient with Severe Cardiogenic Shock: A Propensity-Based Analysis

Background

The best catecholamine regimen for cardiogenic shock has been poorly evaluated. When a vasopressor is required to treat patients with the most severe form of cardiogenic shock, whether inodilators should be added or whether inopressors can be used alone has not been established. The purpose of this study was to compare the impact of these two strategies on short-term mortality in patients with severe cardiogenic shocks.

Methods and Results

Three observational cohorts of patients with decompensated heart failure were pooled to comprise a total of 1,272 patients with cardiogenic shocks. Of these 1,272 patients, 988 were considered to be severe because they required a vasopressor during the first 24 hours. We developed a propensity-score (PS) model to predict the individual probability of receiving one of the two regimens (inopressors alone or a combination) conditionally on baseline-measured covariates. The benefit of the treatment regimen on the mortality rate was estimated by fitting a weighted Cox regression model. A total of 643 patients (65.1%) died within the first 30 days (inopressors alone: 293 (72.0%); inopressors and inodilators: 350 (60.0%)). After PS weighting, we observed that the use of an inopressor plus an inodilator was associated with an improved short-term mortality (HR: 0.66 [0.55–0.80]) compared to inopressors alone.

Conclusions

In the most severe forms of cardiogenic shock where a vasopressor is immediately required, adding an inodilator may improve short-term mortality. This result should be confirmed in a randomized, controlled trial.     

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.     

Outcome at Two Years of Very Preterm Infants Born after Rupture of Membranes before Viability

PurposeTo compare the respiratory and neurological outcomes at two years of age of preterm children born before 33 weeks of gestation (WG) after early preterm premature rupture of membranes (EPPROM) between 14 and 24 WG with preterm children without EPPROM.ResultsNinety-four cases with EPPROM before 24WG have been included. The 31 children born from 26WG to 32WG were matched with 62 controls. The EPPROM group had poorer clinical evaluation at one year for motor (p = 0.003) and cognitive developmental scores (p = 0.016). Neuromotor rehabilitation was performed more often (p = 0.013). However, there was no difference at 2 years of age. Children born after EPPROM were hospitalized more often for bronchiolitis (p<0.001) during their first 2 years, which correlates with increased incidence of pneumothorax (p = 0.017), pulmonary hypoplasia (p = 0.004) and bronchopulmonary dysplasia (p = 0.005) during neonatal period.ConclusionAt two years, despite an increase in severe bronchiolitis and the need for more neuromotor rehabilitation during the first month of the life after discharge, there was no difference in neurological outcomes in the very preterm children of the EPPROM group compared to those born at a similar GA without EPPROM.