Socioeconomic costs of influenza complications in hospitalized children.

Introduction: Influenza may be correlated with a high number of complications and generate high costs of treatment. The study aimed to estimate the socioeconomic significance of hospitalized influenza cases. Material and methods: In the 2015-2016 flu season 157 children (median age 17 months) were hospitalized in the Department of Pediatrics. The diagnosis was confirmed with the rapid influenza diagnostic test (RIDT), polymerase chain reaction (PCR) or both. The study assessed the direct and indirect costs of hospitalization, including the cost of treatment, work absence and the related income lost. Results: The frequency of complications among the children hospitalized was 57.3% (90/157), mainly due to pneumonia (31%) and bronchitis (23%). Patients with complications required longer hospital treatment (8 vs. 6 days, p < 0.01) and generated a higher total cost (€ 1042 vs. € 779, p < 0.01), including the patient's and systemic costs (€123 vs. € 94, p < 0.01 and € 916 vs. € 690, p < 0.01, respectively). Patients with complications had a 3.5-fold higher risk of generating higher (i.e., above median) costs. The difference in the costs between children aged under 2 and those over 2 years old was greater than the difference between children aged under 5 and those over 5 years old (€ 358 vs. € 253). Conclusions: Influenza complications generate higher systemic and patient's costs, both direct and indirect. The group of children for whom the difference is especially marked is under 2 years of age.

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.

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.

Epidemiology of Respiratory Syncytial Virus Hospitalizations in Poland: An Analysis from 2015 to 2023 Covering the Entire Polish Population of Children Aged under Five Years.

BACKGROUND: Respiratory syncytial virus (RSV) is an important cause of childhood hospitalizations. The aim of the study was to estimate the rates of RSV-related hospitalizations in children aged less than 5 years in Poland. METHODS: This retrospective observational cohort study was based on data obtained from the National Health Fund in Poland regarding all acute respiratory tract infections and RSV-coded admissions of children (age < 5 years) to public hospitals between July 2015 and June 2023. Patients were stratified based on the following age groups: 0-1 month, 2-3 months, 4-6 months, 7-12 months, 13-24 months, and 25-60 months. RESULTS: The number of RSV-related hospitalizations increased every season, both before and through the ending phase of the coronavirus disease 2019 (COVID-19) pandemic. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infection. Hospitalization rates per 1000 inhabitants were the highest for children aged 0-12 months, reaching 47.3 in the 2022/23 season. Within this group, the highest hospitalization rate was observed for children aged 2-3 months-94.9 in the 2022/23 season. During the ending phase of the COVID-19 pandemic, the observed increase in admission rates was 2-, 4-, and 5-fold the pre-COVID rate for children aged <12 months, 12-24 months, and 25-60 months, respectively. CONCLUSIONS: In Poland, RSV infections cause a significant burden in hospitalized children aged less than 5 years. RSV-related hospitalizations were most frequent in children aged less than 1 year. The COVID-19 pandemic was associated with a shift in the seasonality pattern of RSV infections. After the pandemic, more RSV-related hospitalizations were observed in older children (aged 13 months and older) vs. the pre-pandemic phase.

PKLR mutations in pyruvate kinase deficient Polish patients: Functional characteristics of c.101-1G > A and c.1058delAAG variants.

Pyruvate kinase (PK) deficiency is a rare autosomal recessive disorder characterized by chronic hemolytic anemia of variable severity. Nine Polish patients with severe hemolytic anemia but normal PK activity were found to carry mutations in the PKLR gene encoding PK, five already known ones and one novel (c.178C > T). We characterized two of the known variants by molecular modeling (c.1058delAAG) and minigene splicing analysis (c.101-1G > A). The former gives a partially destabilized PK tetramer, likely of suboptimal activity, and the c.101-1G > A variant gives alternatively spliced mRNA carrying a premature stop codon, encoding a severely truncated PK and likely undergoing nonsense-mediated decay.

Phase 3 Safety and Immunogenicity Study of a Three-dose Series of Twenty-valent Pneumococcal Conjugate Vaccine in Healthy Infants and Toddlers.

BACKGROUND: Global pediatric immunization programs with pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type pneumococcal disease, but a substantial disease burden of non-PCV serotypes remains. METHODS: This phase 3, randomized (1:1), double-blind study evaluated safety and immunogenicity of 20-valent PCV (PCV20) relative to 13-valent PCV (PCV13) in healthy infants. Participants received 2 infant doses and a toddler dose of PCV20 or PCV13, with diphtheria-tetanus-acellular pertussis combination vaccine at all doses and measles, mumps, rubella and varicella vaccines at the toddler dose. Primary pneumococcal immunogenicity objectives were to demonstrate noninferiority (NI) of PCV20 to PCV13 for immunoglobulin G geometric mean concentrations after infant and toddler doses and percentages of participants with predefined serotype-specific immunoglobulin G concentrations after infant doses. Safety endpoints included local reactions, systemic events and adverse events. RESULTS: Overall, 1204 participants were vaccinated (PCV20, n = 601; PCV13, n = 603). One month after the toddler dose, 19/20 serotypes met NI for immunoglobulin G geometric mean concentrations; serotype 6B narrowly missed NI [PCV20/PCV13 geometric mean ratio: 0.57 (2-sided 95% confidence interval: 0.48-0.67); NI criterion: lower 2-sided 95% confidence interval >0.5]. Sixteen/twenty serotypes met NI for ≥1 primary objective after 2 infant doses. PCV20 induced robust opsonophagocytic activity, and boosting responses were observed for all vaccine serotypes, including those missing statistical NI. The safety/tolerability profile of PCV20 was like that of PCV13. CONCLUSIONS: PCV20 3-dose series in infants was safe and elicited robust immune responses. Based on these results and PCV13 experience, PCV20 3-dose series is expected to be protective for all 20 vaccine serotypes. NCT04546425.

Improving Vaccine Assessment Pathways and Decision Making in the Polish Immunization Program.

This study examines the vaccine market access pathway in Poland to evaluate its efficiency and propose recommendations for its improvement. The research spans a comprehensive analysis of the vaccine assessment process, ranging from pre-registration to sustainability, encompassing critical components such as national immunization technical advisory groups (NITAGs), health technology assessments, resource evaluations, and decision making. This investigation utilizes a multi-phase approach. Initial desk research aimed to collect accumulated evidence about each step of the vaccine access pathway. This constituted the background for an expert panel discussion (n = 13) and a final online questionnaire (n = 12), evaluating the timeframes, inclusiveness, transparency, and consistency of the elements of the process. Poland is a late adopter of new vaccines. The country faces budget constraints and lacks a formalized framework for the inclusion of vaccines into the national immunization program. Notably, NITAGs play a crucial role, yet their limited resources and dependence on public health stakeholders diminish their impact. A formal and well-supported advisory body may become a foundation for decision-making processes. The health technology assessment conducted by the national agency is recognized for its timeliness and transparency, though the absence of fiscal analyses in vaccine assessments is identified as a gap that limits the understanding of the value of vaccinations. Resources are key drivers of decision making, and recent changes in legislation offer increased flexibility in financing vaccines. Challenges in the procurement process include a limited consideration of non-acquisition costs and an increased absence of a documented general strategy for immunization program development in Poland, pointing to a need for strategic planning. In conclusion, this study recommends the establishment of a robust NITAG with enhanced resources, incorporating fiscal analyses, transparent resource allocation, and strategic planning for immunization program development. Addressing these recommendations is crucial for optimizing Poland's vaccine market access pathway, ensuring timely and efficient population-wide vaccine access.

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.

Respiratory Syncytial Virus Infections in Polish Pediatric Patients from an Expert Perspective.

Respiratory syncytial virus (RSV) is the most common pathogen causing respiratory tract infections in infants, affecting over 90% of children within the first two years of life. It may cause lower respiratory tract infections, which constitute a significant healthcare burden both in the primary and secondary care settings. Meanwhile, the data regarding RSV disease in Poland is scarce, and published data significantly differs from the numbers reported for other countries with longstanding surveillance and reporting systems. A literature review and an expert panel were conducted to (1) understand the healthcare burden of RSV infections in Poland; (2) collect data on infection seasonality, patient pathway, and management patterns; and (3) evaluate RSV infection surveillance in Poland. According to the literature, RSV is the major agent responsible for non-influenza respiratory diseases in Poland. The reported rates of hospitalization for RSV infections are 267.5/100,000 for children under 5 years of age and 1132.1/100,000 for those under 1 year of age. Comparisons with data from other countries suggest that these values may be underestimated, possibly due to insufficient access to microbiological testing and a low awareness of RSV. Infections occur mainly between December and April, however, this pattern has changed following the implementation of preventive measures for coronavirus disease 2019 in the past few years. According to available reports, bronchodilators, antibiotics, corticosteroids, and X-ray imaging have been frequently used. The surveillance system in Poland has limitations, but these may be overcome due to recent changes in healthcare law as well as the availability and reimbursement of diagnostic tests.

Key Considerations during the Transition from the Acute Phase of the COVID-19 Pandemic: A Narrative Review.

The COVID-19 pandemic has been met with an unprecedented response from the scientific community, leading to the development, investigation, and authorization of vaccines and antivirals, ultimately reducing the impact of SARS-CoV-2 on global public health. However, SARS-CoV-2 is far from being eradicated, continues to evolve, and causes substantial health and economic burdens. In this narrative review, we posit essential points on SARS-CoV-2 and its responsible management during the transition from the acute phase of the COVID-19 pandemic. As discussed, despite Omicron (sub)variant(s) causing clinically milder infections, SARS-CoV-2 is far from being a negligible pathogen. It requires continued genomic surveillance, particularly if one considers that its future (sub)lineages do not necessarily have to be milder. Antivirals and vaccines remain the essential elements in COVID-19 management. However, the former could benefit from further development and improvements in dosing, while the seasonal administration of the latter requires simplification to increase interest and tackle vaccine hesitancy. It is also essential to ensure the accessibility of COVID-19 pharmaceuticals and vaccines in low-income countries and improve the understanding of their use in the context of the long-term goals of SARS-CoV-2 management. Regardless of location, the primary role of COVID-19 awareness and education must be played by healthcare workers, who directly communicate with patients and serve as role models for healthy behaviors.

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.

Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20-30 ng/mL (50-75 nmol/L)], and optimal concentration [30-50 ng/mL (75-125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

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.

A tendency to worse course of multisystem inflammatory syndrome in children with obesity: MultiOrgan Inflammatory Syndromes COVID-19 related study.

Background: A new disease entity called multisystem inflammatory syndrome in children (MIS-C) is a rare consequence of COVID-19 infection. The pathophysiology and risk factors of MIS-C are still unclear, and the clinical manifestation ranges from milder forms to cases needing intensive care unit treatment. Based on available data, obesity is linked to pro-inflammatory stimulation. Moreover, several studies showed that obesity could play a role in COVID-19 severity and its comorbidities among the adult and children's populations. This study aimed to investigate the influence of overweightedness/obesity in childhood for the course of MIS-C in Poland. Methods: This study presented data from the national MultiOrgan Inflammatory Syndromes COVID-19 Related Study (MOIS-CoR) collected between 4 March 2020 and 20 February 2021. Of the 371 patients that met the Polish MIS-C criteria, 306 were included for further analysis. Results: Children who are obese (OB with body mass index (BMI) ≥95th percentile) and overweight (OV with BMI ≥85th percentile but <95th percentile) (28 and 49 patients, respectively) represented 25.1% (n=77) of all recruited patients. Complete recovery at the time of discharge presented in 93% of normal body weight (NW) participants and 90% of OV children (p>0.05). Among OB children, 76% recovered fully, which differed from the NW group (p=0.01). Calculated odds ratio (OR) of incomplete recovery for OB children was 4.2. Irrespective of body weight, there were no differences (p>0.05) in the length of hospitalization and the duration of symptoms (for OB, 13 and 16.5 days; for OV and NW, 10 and 14 days, respectively), as well as in the frequency of cardiovascular abnormalities, necessity of oxygen therapy (OB, 26.9%; OV, 23.9%; and NW, 20.7%), and intravenous immunoglobulin and glucocorticosteroid (GCS) treatment. Conclusion: The higher risk of incomplete recovery and observed tendency toward a worsening course of MIS-C in patients with obesity suggest the need for further studies to confirm and understand our findings.

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.

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.

Childhood Obesity: Position Statement of Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes, the College of Family Physicians in Poland and Polish Association for Study on Obesity.

Childhood obesity is one of the most important problems of public health. Searching was conducted by using PubMed/MEDLINE, Cochrane Library, Science Direct, MEDLINE, and EBSCO databases, from January 2022 to June 2022, for English language meta-analyses, systematic reviews, randomized clinical trials, and observational studies from all over the world. Five main topics were defined in a consensus join statement of the Polish Society of Pediatrics, Polish Society for Pediatric Obesity, Polish Society of Pediatric Endocrinology and Diabetes and Polish Association for the Study on Obesity: (1) definition, causes, consequences of obesity; (2) treatment of obesity; (3) obesity prevention; (4) the role of primary care in the prevention of obesity; (5) Recommendations for general practitioners, parents, teachers, and regional authorities. The statement outlines the role of diet, physical activity in the prevention and treatment of overweight and obesity, and gives appropriate recommendations for interventions by schools, parents, and primary health care. A multisite approach to weight control in children is recommended, taking into account the age, the severity of obesity, and the presence of obesity-related diseases. Combined interventions consisting of dietary modification, physical activity, behavioral therapy, and education are effective in improving metabolic and anthropometric indices. More actions are needed to strengthen the role of primary care in the effective prevention and treatment of obesity because a comprehensive, multi-component intervention appears to yield the best results.