A noninferiority randomized open-label pilot study of 3- versus 7-day influenza postexposure prophylaxis with oseltamivir in hospitalized children.

Short influenza postexposure prophylaxis (PEP) showed high efficacy in adults, but studies in children are lacking. This randomized open-label pilot trial aimed to verify noninferiority of a 3- versus 7-day prophylaxis with oral oseltamivir in hospitalized children. Influenza contacts were randomized to the 3- or 7-day group and efficacy, relative risk of adverse events (AEs), and the cumulative costs of drugs and AEs management were compared. The intention-to-treat (ITT) analysis included 59 children (n = 28 and n = 31 in the 3- and 7-day group, respectively). The efficacy was 100% (95% CI 87.7-100%) versus 93.6% (95% CI 78.6-99.2%) in the 3- and 7-day group; the differences were statistically insignificant. A per-protocol (PP) analysis including 56 patients (n = 27 and n = 29, respectively) showed 100% (95% CI 87.2-100%) and 93.1% (95% CI 77.2-99.2%) efficacy, respectively, without statistical significance. Differences were within the predefined noninferiority margin with an efficacy difference Δ = 6.45 percentage points (p.p.) with 1-sided 95% CI (- 2.8, - 1.31, p = 0.86; ITT) and Δ = 6.9 p.p. (1-sided 95% CI - 2.83, - 1.27, p = 0.85; PP). Adverse events did not differ significantly, while the cumulative costs of the prophylaxis and AEs management were higher in the 7-day group (median 10.5 euro vs. 4.5 euro, p < 0.01). This pilot study showed the noninferiority of the 3-day versus 7-day PEP, which was associated with lower costs.Trial registration number: NCT04297462, 5th March 2020, restrospectively registered.

Molecular Mechanisms of N-Acetylcysteine in RSV Infections and Air Pollution-Induced Alterations: A Scoping Review.

N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.

Significant COVID-19 burden in Polish children.

Introduction: COVID-19 cases have rarely been reported in children. We sought to analyse the attack rate in paediatric population in Poland, focusing on local variations among the provinces, correlation with the number of tests per capita, and test positivity rate. Material and methods: This cross-sectional study involved the 38.38 million population and detected 17,921 cases (age known in 17,822). Data were collected from publicly available registries and were analysed by age group and province of the country. Results: Children constituted 6.68% of cases (n = 1,191). The attack rate reached 15.49/100,000 children, increasing with age (10.79/100,000 in < 4 y.o. to 21.59/100,000 in 15-19 y.o.). Significant variations in the attack rates were observed: a 9.52-fold ratio between the highest and the lowest attack rates in provinces. The provinces from the first and fourth attack rate quartiles differed in the test positivity rate (4.96% vs. 1.98%, p < 0.05), but not in the number of tests per capita. The lowest quartile provinces showed 1.87- to 5.78-fold lower attack rates, compared to the directly neighbouring provinces, without any known population susceptibility differences. The attack rates in children and adults correlated very strongly (rho = 0.81). The attack rate correlated with the test positivity rate (rho = 0.64 in children and rho = 0.71 in adults) but not with the number of tests per capita. Conclusions: COVID-19 burden in children is significant. The local differences highlight various testing strategies, but the awareness of SARS-CoV-2 in children is essential. The correlation between attack rates in children and adults shows that the outbreak in children is parallel to the one observed in adults.

The Estimate of Parental Quality of Life Loss Due to Respiratory Syncytial Virus (RSV) Hospitalization.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the leading causes of pediatric hospitalizations, mainly in children under 2 years of age. Hospitalization affects the caregivers' quality of life (QoL). We assessed the caregivers' QoL during RSV-confirmed hospitalizations of children under 2 years old, identified the most affected QoL dimensions and calculated utilities focusing on the assessment methods and potential confounders. METHODS: The caregivers filled out the EQ-5D questionnaire, consisting of a descriptive system (assessing 5 QoL dimensions) and a visual analog scale (EQ VAS). Utility, utility loss and quality-adjusted life years (QALY) loss were calculated, and a concordance between the two systems was assessed. RESULTS: A disturbance in any of the five assessed dimensions was reported by 42% (55 out of 132) of the caregivers, mostly anxiety/depression (37%) and pain/discomfort (17%). The utilities varied between 0.17 and 1 in the descriptive system and 0.33-1 (median 0.86) in the EQ VAS, with a utility loss of 0.14 (IQR: 0.1-0.2). The calculated QALY loss reached a median of 2.45 × 10-3 (IQR: 1.37 × 10-3-4.56 × 10-3) and was not influenced by the patient's age or the final clinical diagnosis (QALY loss for bronchiolitis: 2.74 × 10-3, pneumonia: 1.84 × 10-3, bronchitis: 1.78 × 10-3, differences statistically insignificant). Only a moderate concordance between the descriptive system and the EQ VAS was seen (Spearman's rank correlation coefficient = 0.437, p < 0.05), with the latter revealing a higher degree of QoL disturbances. CONCLUSIONS: RSV hospitalization influences parental QoL significantly, and anxiety/depression is the most commonly reported issue. Utility impairment scores depend on the assessment method but not on the patient's age or final diagnosis. Thus, the impact of RSV on caregivers' QoL cannot be underestimated.

The Impact of RSV Hospitalization on Children's Quality of Life.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the most frequent etiological factors of lower respiratory tract infections in children, potentially affecting patients' quality of life (QoL). We aimed to asses QoL in children under 2 years of age hospitalized due to laboratory-confirmed RSV infection. METHODS: A QoL was assessed by parents/tutors with the use of the 100-point visual analog scale and compared against a disease-free period. We evaluated the median utility, QoL loss (reported in days), and quality-adjusted life years (QALY) loss in relation to RSV hospitalization. RESULTS: We included 132 patients aged from 17 days to 24 months (median 3.8 months). The mean utility during the hospitalization varied between 0.418 and 0.952, with a median of 0.679 (95%CI: 0.6-0.757) and median loss of 0.321 [0.243-0.4], which further translated into a loss of 2.2 days (95%CI: 1.6-3.1). The QALY loss varied between 0.526 × 10-3 and 24.658 × 10-3, with a median of 6.03 × 10-3 (95%CI: 4.38-8.48 × 10-3). Based upon the final diagnoses, the highest QALY loss was 6.99 × 10-3 (95%CI: 5.29-13.7 × 10-3) for pneumonia, followed by bronchiolitis-5.96 × 10-3 (4.25-8.41 × 10-3) and bronchitis-4.92 × 10-3 (2.93-6.03 × 10-3); significant differences were observed only between bronchitis and pneumonia (p = 0.0171); the QALY loss was not age-dependent. Although an increasing tendency in the utility score was observed, a strong cumulative effect related to the length of stay was noted until day 13. CONCLUSIONS: RSV contributes significantly to the utility deterioration and QALY loss in the case of RSV hospitalization, and the patient-reported data should be used in pharmacoeconomic assessments of the impact of RSV.

Risk Factors for Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: RSV often leads to hospitalization, and accurate knowledge of risk factors is crucial. METHODS: We retrospectively analyzed laboratory-confirmed RSV hospitalizations regarding pregnancy factors, birth status, cigarette smoke exposure, nutrition, social conditions, clinical presentation, and severe disease defined as a need for passive oxygen therapy (pO2Tx), the presence of pneumonia, respiratory failure, intensive care unit (ICU) transfer, and prolonged hospitalization. RESULTS: A univariate analysis included 594 children (median age 4 months) and revealed a pO2Tx relationship with age ≤ 3 months (OR = 1.56), prematurity (OR = 1.71), being born during RSV season (OR = 1.72), smoke exposure during pregnancy (both parents (OR = 2.41, father (OR = 1.8)), dyspnea (OR = 5.09), and presence of apnea (OR = 5.81). Pneumonia was associated with maternal smoke exposure (OR = 5.01), fever (OR = 3.92), dyspnea (OR = 1.62), history of aspiration (OR = 4.63), and inversely with age ≤ 3 months (OR = 0.45). Respiratory failure was associated with prematurity (OR = 3.13) and apnea (OR = 18.78), while the lower odds were associated with older age (OR = 0.57 per month) and presence of fever (OR = 0.11). ICU transfer was associated with apnea (OR = 17.18), but an inverse association was observed with age (OR = 0.54) and fever (OR = 0.11). A prolonged hospital stay was associated with prematurity (OR = 1.76), low birth weight (OR = 2.89), aspiration (OR = 4.93), and presence of fever (OR = 1.51). CONCLUSIONS: Age (up to 3 months), prematurity, and presence of apnea are risk factors for a severe RSV course.

Platelet Abnormalities in Children with Laboratory-Confirmed Influenza.

BACKGROUND: The role of platelets in the immune response against influenza has been raised, and a diagnostic or prognostic value of platelet parameter abnormalities, including platelet count (PLT), or mean platelet volume (MPV), has been suggested. The study aimed to analyze the prognostic value of platelet parameters in children hospitalized due to laboratory-confirmed influenza. METHODS: We retrospectively verified the platelet parameters (PLT, MPV, MPV/PLT, and PLT/lymphocyte ratio regarding the influenza complications (acute otitis media, pneumonia, and lower respiratory tract infection-LRTI), and the clinical course (antibiotic treatment, tertiary care transfer, and death). RESULTS: An abnormal PLT was observed in 84 out of 489 laboratory-confirmed cases (17.2%, 44 thrombocytopaenia cases, and 40 thrombocytoses). Patients' age correlated negatively with PLT (rho = -0.46) and positively with MPV/PLT (rho = 0.44), while MPV was not age-dependent. The abnormal PLT correlated with increased odds of complications (OR = 1.67), including LRTI (OR = 1.89). Thrombocytosis was related to increased odds of LRTI (OR = 3.64), and radiologically/ultrasound-confirmed pneumonia (OR = 2.15), mostly in children aged under 1 year (OR = 4.22 and OR = 3.79, respectively). Thrombocytopaenia was related to antibiotic use (OR = 2.41) and longer hospital stays (OR = 3.03). A lowered MPV predicted a tertiary care transfer (AUC = 0.77), while MPV/PLT was the most versatile parameter in predicting LRTI (AUC = 0.7 in <1 yo), pneumonia (AUC = 0.68 in <1 yo), and antibiotic treatment (AUC = 0.66 in 1-2 yo and AUC = 0.6 in 2-5 yo). CONCLUSIONS: Platelet parameters, including PLT count abnormalities and MPV/PLT ratio, are related to the increased odds of complications and a more severe disease course, and may add important data in assessing pediatric influenza patients, but should be interpreted cautiously due to age-related specificities.

The Etiology of Community-Acquired Pneumonia Correlates with Serum Inflammatory Markers in Children.

Community-acquired pneumonia (CAP) severely affects pediatric hospitalizations. This study assessed the contribution of CAP to hospitalizations, its etiology in relationship with age, and the inflammatory markers. Between 2013 and 2018, 1064 CAP patients were hospitalized and diagnosed with bacterial/possibly bacterial pneumonia (BP), viral/possibly viral pneumonia (VP) and atypical pneumonia (AP). The etiology was confirmed using blood/pleural fluid culture/polymerase chain reaction (PCR), rapid antigen test/PCR in nasopharyngeal swabs, or serological studies. CAP accounted for 9.9% of hospitalizations and 14.8% of patient days. BP was diagnosed in 825 (77.5%), VP in 190 (17.9%), and AP in 49 (4.6%) cases; the confirmed etiology (n = 209; 20%) included mostly influenza (39%; n = 82), respiratory syncytial virus (RSV, 35%; n = 72), and Mycoplasma pneumoniae (19%; n = 39). VP frequency decreased with age (41% in < 3 mo to 9% in ≥ 60 mo), in contrast to AP (13% in ≥ 60 mo). Among the analyzed parameters, the best differentiating potential was shown by: C-reactive protein (CRP, AUCBP-VP = 0.675; 95% CI: 0.634−0.715), procalcitonin (AUCBP-AP = 0.73; 95% CI: 0.67−0.794), and CRP/procalcitonin (AUCAP-VP = 0.752; 95% CI: 0.67−0.83); a good positive predictive value (88.8%, 98.3%, and 91.6%, respectively) but a low negative predictive value (29.5%, 13.1%, and 40.7%, respectively) was observed. CAP influences hospital patient days more than the crude number of patients would suggest. On a clinical basis, BP is mainly recognized, although viral pneumonia is confirmed most often. RSV and influenza are responsible for a huge percentage of hospitalized cases, as well as M. pneumoniae in children aged ≥ 5 years. Serum inflammatory markers may help differentiate etiological factors.

Capillary Blood Gas in Children Hospitalized Due to Influenza Predicts the Risk of Lower Respiratory Tract Infection.

Background: Influenza may impair respiratory exchange in the case of lower respiratory tract infections (LRTIs). Capillary blood gas (CBG) reflects arterial blood values but is a less invasive method than arterial blood sampling. We aimed to retrospectively verify the usefulness of CBG in pediatric influenza. Material and methods: CBG parameters (pH, pCO2, pO2, SatO2) in laboratory confirmed influenza cases hospitalized in 2013−2020 were verified in terms of LRTI, chest X-ray (CXR) performance, radiologically confirmed pneumonia (CXR + Pneumonia), prolonged hospitalization, and intensive care transfer. A theoretical CBG-based model for CXR performance was created and the odds ratios were compared to the factual CXR performance. Results: Among 409 children (aged 13 days−17 years 3/12, median 31 months), the usefulness of CBG decreased with the age. The SatO2 predicted the LRTI with AUC = 0.74 (95%CI: 0.62−0.86), AUC = 0.71 (0.61−0.82), and AUC = 0.602 (0.502−0.702) in children aged <6 months old (mo), 6−23 mo, 24−59 mo, respectively, while pO2 revealed AUC = 0.73 (0.6−0.85), AUC = 0.67 (0.56−0.78), and AUC = 0.601 (0.501−0.702), respectively. The pCO2 predicted the LRTI most precisely in children <6 months with AUC = 0.75 (0.63−0.87), yet not in older children. A high negative predictive value for CXR + Pneumonia was seen for SatO2 < 6 mo (96.7%), SatO2 6−23 mo (89.6%), pO2 < 6 mo (94.3%), pO2 6−23 mo (88.9%). The use of a CBG-driven CXR protocol (based on SatO2 and pO2) would decrease the odds of an unnecessary CXR in children <2 years old (yo) by 84.15% (74.5−90.14%) and 86.15% (66.46−94.28%), respectively. SatO2 and pO2 also predicted a prolonged hospitalization <6 mo AUC = 0.71 (0.59−0.83) and AUC = 0.73 (0.61−0.84), respectively, and in 6−23 mo AUC = 0.66 (0.54−0.78) and AUC = 0.63 (0.52−0.75), respectively. Conclusions: The CBG is useful mainly in children under two years, predicts the risk of LRTI, and can help exclude the risk of CXR + pneumonia. Children under six months of age represent the group that would benefit the most from CBG. A CBG-based protocol for the performance of CXR could significantly decrease the number of unnecessary CXRs.

Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review.

RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants-RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV-air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations.

Influence of Selected Air Pollutants on Mortality and Pneumonia Burden in Three Polish Cities over the Years 2011-2018.

Poland has one of the worst air qualities in the European Union, particularly regarding concentrations of particulate matter (PM). This study aimed to evaluate the short-term effects of air pollution and weather conditions on all-cause mortality and pneumonia-related hospitalizations in three Polish agglomerations. We investigated data from 2011 to 2018 on a number of health outcomes, concentrations of PM2.5, PM10, nitrogen dioxide (NO2), ozone (O3), and selected meteorological parameters. To examine the impact of air pollutants and weather conditions on mortality and pneumonia burden, we identified optimal general regression models for each agglomeration. The final models explained <24% of the variability in all-cause mortality. In the models with interactions, O3 concentration in Warsaw, NO2, O3, and PM2.5 concentrations in Cracow and PM10 and O3 concentrations in the Tricity explained >10% of the variability in the number of deaths. Up to 46% of daily variability in the number of pneumonia-related hospitalizations was explained by the combination of both factors, i.e., air quality and meteorological parameters. The impact of NO2 levels on pneumonia burden was pronounced in all agglomerations. We showed that the air pollution profile and its interactions with weather conditions exert a short-term effect on all-cause mortality and pneumonia-related hospitalizations. Our findings may be relevant for prioritizing strategies to improve air quality.

Low Levels of Procalcitonin Are Related to Decreased Antibiotic Use in Children Hospitalized Due to Influenza.

Procalcitonin increases in bacterial infections, which are often suspected (though rarely confirmed) in paediatric influenza. We retrospectively verified procalcitonin's usefulness in antibiotic guidance in children hospitalized due to laboratory-confirmed influenza. The ROC curve analysis evaluated procalcitonin's performance in terms of antibiotic implementation or continuation in patients who were naive or had been receiving antibiotic treatment prior to hospital admission. We also assessed the procalcitonin's usefulness to predict lower-respiratory-tract infections (LRTI), the presence of radiologically confirmed pneumonia, an intensive care unit transfer and a fatal outcome. Multiple regression models were built to verify the previously reported procalcitonin cut-off values. The study enrolled 371 children (median age 33 months). The AUC (area under the curve) for antibiotic implementation reached 0.66 (95%CI: 0.58-0.73) and 0.713 (95%CI: 0.6-0.83) for antibiotic continuation; optimal cut-offs (0.4 and 0.23 ng/mL, respectively) resulted in a negative predictive value (NPV) of 79.7% (95%CI: 76.2-82.9%) and 54.6% (95%CI: 45.8-63%), respectively. The use of 0.25 ng/mL as a reference decreased the odds of antibiotic treatment by 67% (95%CI: 43-81%) and 91% (95%CI: 56-98%), respectively. Procalcitonin showed lower AUC for the prediction of LRTI and pneumonia (0.6, 95%CI: 0.53-0.66, and 0.63, 95%CI: 0.56-0.7, respectively), with a moderately high NPV in the latter case (83%, 95%CI: 79.3-86.1%). Procalcitonin use may decrease the antibiotic frequency in hospitalized influenza cases both in terms of antibiotic administration and continuation. Procalcitonin concentrations may suggest bacterial suprainfections at lower concentrations than in adults, and a focus on its rule-out value is of special interest.

Air Pollutants' Concentrations Are Associated with Increased Number of RSV Hospitalizations in Polish Children.

Respiratory syncytial virus (RSV) contributes significantly to pediatric hospitalizations. An association between air pollution and an increased number of RSV cases has been suggested. We sought to evaluate the short-term impact of air pollutants on RSV hospitalizations in Polish children in the period 2010-2019. Daily concentrations of PM10 and PM2.5 (particulate matter with an aerodynamic diameter less than or equal to 10 µm and 2.5 µm, respectively) and nitrogen dioxide (NO2) were analyzed in general regression models (GRM) to establish their influence and full interaction scheme. Significant seasonal and annual periodicity among 53,221 hospitalizations was observed; finally, data from the 2012-2019 RSV high-risk seasons created models for seven agglomerations. The addition of PM2.5, PM10, and NO2 to the basic model for RSV seasonality explained 23% (4.9-31%, univariate model) to 31.4% (8.4-31%, multivariate model) of the variance in RSV hospitalizations. A 10 µg/m3 increase in PM2.5, PM10, and NO2 concentrations was associated with 0.134 (0.087-0.16), 0.097 (0.031-0.087), and 0.212 (0.04-0.29) average increases in hospitalizations, respectively. In the multivariate models, PM2.5, PM10, and NO2 alone, as well as PM2.5-NO2, PM2.5-PM10, and PM10-NO2 interactions, were associated with hospitalizations in some of the locations, while the metaregression showed statistically significant interactions between each of the pollutants, and between the pollutants and the year of the study. The inclusion of PM2.5, PM10, and NO2 in GRM explains a significant number of RSV hospitalizations. The pollutants act alone and interact together in a varied manner. Reducing air contamination might decrease the costs of hospital healthcare.

Capillary Blood Gas Predicts Risk of Intensive Care in Children with Bronchiolitis.

BACKGROUND: Bronchiolitis may result in respiratory failure diagnosed with arterial blood gas (ABG). ABG is not routinely performed in general paediatric wards but is closely reflected by capillary blood gas (CBG). We sought to assess the usefulness of CBG results in prediction of intensive care unit (ICU) transfer, antibiotic treatment, and length of stay in children hospitalized due to bronchiolitis. METHODS: The optimal cutoff values were estimated with an ROC analysis, while a multiple regression model calculated the odds of an ICU transfer, prolonged hospitalization, and antibiotic treatment related with hypercapnia (pCO2 ≥ 45 mmHg) and acidosis (pH ≤ 7.35). The correlation between the CBG (pH, pCO2, and SatO2) and the clinical/laboratory parameters (breath rate, heart rate, pulse oximetry, white blood cells, CRP, and procalcitonin) was calculated. RESULTS: The CBG was performed in 485 children aged 8 days-22 months (median 2 months). The pCO2 was significantly higher in ICU transferred patients (median 44.8 mmHg vs. 36.2 mmHg, p < 0.01), and showed AUC = 0.773, (95% CI: 0.638-0.907, p < 0.01) for ICU transfer (67% sensitivity, 82% specificity, 10.8% positive and 98.7% negative predictive value at cutoff 41.8 mmHg). Hypercapnia (OR = 6.63, 95% CI: 2.15-20.46, p < 0.01) and acidosis (OR = 5.01, 95% CI: 1.26-19.9, p = 0.022) predicted the ICU transfer independently. The CBG parameters were not related to prolonged hospitalization or antibiotic treatment, and showed only a weak and clinically irrelevant correlation with other laboratory and clinical parameters. CONCLUSIONS: Acidosis and hypercapnia indicate patients at risk of an ICU transfer, and the pCO2 levels (including values lower than hypercapnia) seem to be a promising marker in ICU risk assessment.

Respiratory Complications in Children Hospitalized with Respiratory Syncytial Virus Infection.

The goal of this study was to define the prevalence of respiratory complications, other than bronchiolitis, such as pneumonia, acute otitis media, and conjunctivitis in children treated in a hospital due to respiratory syncytial virus (RSV) infection, with reference to the plausible risk factors. The study included 111 children, aged up to 22 months (median 3 months). Complications were observed in 68 (61%) children, with 32 (29%) children presenting more than one. The most frequent complication was acute otitis media in 53 (48%), pneumonia in 37 (33%), and conjunctivitis in 12 (11%) out of the 111 children. Children with complications were older than those without complications and had fever that lasted for a significantly longer time, both before and during hospitalization, and the fever was stronger. They also presented a significantly lower breathing rate at admission. The age over 3 months was a single risk factor associated with the development of otitis media (OR = 9.8, 95%CI: 3.6-26.7) and pneumonia (OR = 2.8, 95%CI: 1.1-7.3). Other factors such as prematurity, birth weight below 2500 g, exposure to tobacco smoke during pregnancy, and the cessation of breastfeeding below age 6 months were statistically irrelevant to this end. We conclude that complications are very frequent in hospitalized children with RSV infection and their risk increases with the infant age.

Bacteremia in Children Hospitalized Due to Respiratory Syncytial Virus Infection.

The frequency of bacteremia in children hospitalized due to respiratory syncytial virus infection (RSV) rarely exceeds 1%, but a recent study reported a 10% risk of bacteremia. In this study, we set out to verify the frequency, usefulness, and costs of blood cultures in RSV infections. We addressed the issue by reviewing medical files of 512 children, aged 8 days-121 months, who were hospitalized during January 2010 and June 2017. The RSV-related diagnoses included bronchiolitis (390 patients), RSV pneumonia (65 patients), and bronchitis (57 patients). There were 212 blood cultures performed in 185 patients (36%). In 10 cultures (5.4%), the following pathogens were identified: Staphylococcus haemolyticus, 4; Staphylococcus epidermidis, 1; Staphylococcus hominis, 1; Corynebacterium, 1 Streptococcus parasanguinis, 1; Rothia mucilaginosa, 1; Micrococcus luteus, 1; and Streptococcus hominis, 1 case. However, all of these pathogens were identified as a contamination of samples only. Therefore, both positive blood cultures turned out in fact negative, and the patients having either result of blood culturing showed no clinically relevant differences. The total cost of blood cultures in the pediatric ward amounted to €1980. If performed in each and every patient, the costs would have reached €5490. In conclusion, the frank frequency of bacteremia in children with RSV infection, with no sepsis, seems exceedingly low, which confirms the earlier findings. Thus, blood culturing, generating high costs, is of negligible clinical value. The study provides no evidence supporting a routine blood culture in case of children hospitalized due to RSV infection.

Seasonality of Respiratory Syncytial Virus Hospitalization.

Seasonality of respiratory syncytial virus (RSV) infection is an area of limited knowledge. In this study, we set out to get insight into the epidemic characteristics of RSV. We retrospectively evaluated medical files of 512 hospitalizations in children due to RSV infection from January 2010 to July 2017. In this cohort of patients, there were 96.3% of children below 1 year of age; the median age was 2.8 months. The influence of weather condition during the week of hospitalization (WH) and also the preceding week (WP) on the rate of hospitalizations was also assessed. An overview of morbidity data demonstrates that the epidemic RSV season started from Week 50 of a year and lasts until Week 15 of the following year, with a peak between Week 4 and Week 10. The average monthly percentage rate of morbidity per year was as follows: December, 12.3%; January, 24.5%; February, 29%; and March, 21.7%. Hospitalizations were positively associated with the minimum and maximum outside air temperature during the WH (62.5% and 59.7%, respectively) and the WP (64.3% and 63.4%, respectively) and with relative humidity (WH 23% and WP 29.8%). A weak association with the wind speed was also noticed (WH 22% and WP 21%), while there was no influence of the level of atmospheric pressure on RSV morbidity. We conclude that seasonality of RSV is present between December and April each year, and morbidity is mostly influenced by minimum-maximum outside air temperature changes. Further epidemiological exploration is required to get a better knowledge on both active and passive immunization against RSV.

Nosocomial Infections in Patients Hospitalized with Respiratory Syncytial Virus: A Practice Review.

Viral testing is not always recommended in children with bronchiolitis due to doubts concerning its prognostic use. In this retrospective study, we investigated how the RSV testing would influence the frequency of nosocomial infections (NI). The files of 305 children, hospitalized due to the respiratory syncytial virus (RSV) infection in the period 2010-2014, were reviewed in the study. We found ten cases of NI. The RSV preventive measures did not vary in the consecutive years investigated, but the number of viral tests substantially varied. In 2010, 2012, and 2014, when ca. 2 tests per RSV(+) patient were performed, the risk of NI per patient was 1.3%, while in 2011 and 2013, when the RSV testing was less frequent, the accumulated risk per patient was 5.2%. There was a strong adverse relationship between the number of tests performed and the number of NI (rho = -0.975). The children with NI, when compared to those without NI, required a longer hospital stay, generating higher hospital costs regarding treatment, productivity loss, and indirect costs. The expenditure for RSV testing in the years of a low NI risk was higher than that in the high-risk years. Conversely, the expenditure related to NI management was lower in the years of a low NI risk. Each euro spent on RSV testing saved over 26 € from the NI management expenditure. We conclude that RSV testing is needed in the hospital setting to isolate the infected children and to prevent nosocomial RSV spread. This strategy is health advantageous and requires less resources than NI treatment.

Chest Radiography in Children Hospitalized with Bronchiolitis.

In uncomplicated bronchiolitis, chest radiography (CR) is not routinely recommended, yet it is still frequently made. This study seeks to evaluate the use of CR in children with bronchiolitis due to a lower respiratory tract infection (RSV-RTI) with respiratory syncytial virus (RSV) and the influence of CR on patient treatment during the 2010-2017 seasons. There were 581 children included into the study: 459 with bronchiolitis (390 RSV-RTI and 69 non-RSV), 65 with RSV pneumonia and 57 with RSV bronchitis. We found that CR was performed in 28.6% (166/581) patients. CR was much more frequent in patients with RSV than non-RSV infections (61% vs. 31%). CR prognostic sensitivity and specificity in guiding antibiotic treatment was low, 78% and 58%, respectively. Positive and negative predicted values of CR were 78% and 58%, respectively and the number needed to diagnose was 2.777. Children in whom CR was performed (irrespective of the result) were at 22.9-fold higher risk of antibiotic therapy (95%CI: 14.1-37.1; p < 0.01), while those with a positive CR were only at 4.4-fold higher risk of antibiotic therapy (95%CI: 2.2-8.9; p < 0.01). Children with CR required a longer hospital stay than those without it (10 vs. 8 days, respectively; p < 0.01). The percentage of CR decreased from 78% in 2010 to 33% in 2017, with the lowest value of 11% in 2015. The additional cost of CR, which had no influence on treatment, would have been €381 had it been performed in each patient, which amounts to 1% of the total hospitalization cost. We conclude that CR is overused and in most cases it has no influence on the patient management. The recognition of practical meaning of CR is essential to avoid unnecessary radiation of children.

Antibiotic Treatment in Patients with Bronchiolitis.

This study seeks to define the indications and the economic impact of the use of antibiotics in infants hospitalized due to bronchiolitis during 2010-2017. There were 459 children with bronchiolitis, median age of 2.2 months, 390 infections with respiratory syncytial virus (RSV), and 69 were non-RSV. Twenty two percent of all these children (102/459) required a workup toward urinary tract co-infections (UTI). A control group, consisting of 8,456 children without bronchiolitis, was created to assess UTI frequency in the general population. We found that 16.0% (73/459) children with bronchiolitis received antibiotics; 63 (13.7%) due to respiratory infection and 9 due to UTI. A time-trend analysis showed a decreasing use of antibiotics, from 57.0% in 2010 to 13.7% in 2017, with the lowest value of 6.4% noticed in 2014. Children treated with antibiotics required a 4-day longer hospitalization than those untreated (p < 0.01), but there were no other clinically relevant differences. After excluding the first 2 years with the highest antibiotic ordering, antibiotics, on average, were used in 9.8% of children with bronchiolitis. Frequency of UTI accompanying bronchiolitis was comparable to that in the control group (8.9% vs. 10.9%, respectively). Specificity of urine culture was 71%, with 100% sensitivity assumed, while the positive predicted value of only 41%. The unnecessary costs of urine cultures, if performed in each patient, would have been €2,236, and with additional laboratory tests in each case of a false positive result it would have reached €5,448. We conclude that antibiotics should be used for bronchiolitis only in justified cases, and their use should not exceed 10% of patients. Since UTI is no more frequent in bronchiolitis than in the general children's population, urine cultures should not be performed routinely.