Serum HMGB1 in febrile seizures.

The role of high-mobility group box 1 (HMGB1) in the pathogenesis of febrile seizures (FSs) is unclear. In our controlled follow-up study, we compared serum levels of HMGB1 (s-HMGB1) in the same individuals after the first FS, during febrile episodes without a FS, after recurrent FS, during healthy periods after FS, and between patients and controls. In all, 122 patients with FSs were included in the final analysis, including 18 with recurrent FSs with a complete follow-up protocol. We recruited 30 febrile children and 18 matched febrile children without seizures as controls. S-HMGB1 was lower in patients with recurrent FSs after the first FS than that in matched febrile control children (median 1.12 µg/L (0.14-2.95) vs 1.79 µg/L (0.33-47.90), P<0.04). We did not find any other differences in s-HMGB1 between the groups. S-HMGB1 did not differ in different types of FSs. We updated a meta-analysis of s-HMGB1 in patients with FSs and found that the differences were significant only in the studies conducted in East Asian populations. We conclude that S-HMGB1 does not seem to be a key factor in the pathogenesis of FSs but differences in HMGB1 concentrations could explain some of the ethnicity related susceptibility to FSs.

Streptococcus salivarius Probiotics to Prevent Acute Otitis Media in Children: A Randomized Clinical Trial.

Importance: New approaches for the prevention of acute otitis media (AOM), the most common reason for antibiotic use in children, are needed. Objective: To assess the efficacy of the Streptococcus salivarius K12 oral probiotics in the primary prevention of AOM. Design, Setting, and Participants: This double-blind, randomized placebo-controlled clinical trial was conducted from August 1, 2020, to May 31, 2021, at 50 day care centers in the Oulu region of Finland. A total of 827 children aged 1 to 6 years attending day care were included. The exclusion criteria consisted of ongoing antimicrobial prophylaxis or immunodeficiency. The follow-up time was 6 months and was completed on May 31, 2021. Data were analyzed from October 24, 2022, to September 16, 2023, based on intention to treat. Intervention: Eligible participants were randomly allocated to receive 1 daily dose of a S salivarius K12 product or placebo every evening for 6 months. A daily dose was defined as 1 sachet of soluble oral powder for children younger than 3 years or 1 chewable tablet for children 3 years or older containing 1 × 109 colony-forming units of S salivarius K12. Main Outcomes and Measures: The primary outcome was the proportion of children with at least 1 episode of AOM requiring antimicrobial therapy within 6 months of randomization. All physician visits and purchases of antimicrobial drugs were retrieved from the electronic national medical record and prescription register. The primary outcome was met if the legal guardian had purchased an antimicrobial prescription for AOM. Results: A total of 827 children with a mean (SD) age of 4.1 (1.6) years (433 boys [52.4%]) were randomized to S salivarius K12 oral products (n = 413) or placebo (n = 414). Thirty-four children (8.2%) in the S salivarius group and 24 children (5.8%) in the placebo group experienced at least 1 episode of AOM requiring antimicrobial therapy during the 6-month follow-up period (relative risk, 1.42 [95% CI, 0.86-2.34]; proportion difference, -2.44% [95% CI, -5.94% to 1.09%]; P = .17). Time to first AOM episode did not differ between the groups (174 [95% CI, 171-177] days in the S salivarius group vs 176 [95% CI, 173-179] days in the placebo group; P = .18). Conclusions and Relevance: In this randomized placebo-controlled clinical trial, the daily use of the S salivarius K12 products for 6 months did not reduce the occurrence of AOM. New approaches for primary prevention of AOM among children are needed. Trial Registration: ClinicalTrialsRegister.eu Identifier: 2020-001076-14.

Nasopharyngeal detection of atypical bacteria by multiplex polymerase chain reaction panel in acutely ill children was associated with an increased risk of pneumonia.

AIM: We aimed to assess whether detection of respiratory bacteria by multiplex polymerase chain reaction (PCR) testing associates with clinical outcomes in acutely ill children. METHODS: This cross-sectional study enrolled children under the age of 18 with a suspected respiratory infection treated in a paediatric emergency department of Oulu University Hospital, Finland from January 2015 through December 2015. Nasopharyngeal samples were routinely analysed for 16 respiratory viruses and later, after storage, analysed with a multiplex PCR panel for seven respiratory bacteria. RESULTS: At least one bacterial pathogen was detected in 600 out of the 1195 children (50%). The mean age was 3.3 (SD 3.7) years and 54% were boys. Atypical bacteria were associated with a risk of pneumonia (adjusted odds ratio [aOR] 14.1, 95% CI 3.98-50.1). Co-detection of rhinovirus with Streptococcus pneumoniae was not associated with risk of pneumonia (aOR 2.39, 95% CI 0.78-7.30). Detection of Streptococcus pneumoniae, Haemophilus influenzae or both was not associated with the risk of hospital admission or prescription of antibiotics. CONCLUSION: Nasopharyngeal detection of atypical bacteria in acutely ill children was associated with a markedly increased risk of pneumonia. The clinical utility of wide testing for other respiratory bacteria needs further evaluation.

Recurrent febrile seizures and serum cytokines: a controlled follow-up study.

BACKGROUND: The role of cytokines in the pathogenesis of febrile seizures (FSs) is unclear, and information regarding cytokine production outside of FS episodes is scarce. METHODS: In our controlled follow-up study of patients with FSs, we compared the levels of 12 serum cytokines after the patients' first FSs, during febrile episodes without FSs, after recurrent FSs, during healthy periods after FSs, and between patients and controls. RESULTS: Two-hundred fifty-one patients with first FS participated in the study, of whom 17 (mean age 1.6 years, SD 0.7) with recurrent FSs completed the protocol as required by the sample size calculations. The mean IL-1RA level was higher after the first FSs (2580 pg/mL, SD 1516) than during febrile episodes without FSs (1336 pg/mL, SD 1364, P = 0.006) and healthy periods after FSs (474 pg/mL, SD 901, P = 0.001). IL-1RA levels were also higher during first (2580 pg/mL) and recurrent FSs (2666 pg/mL, SD 1747) in comparison with febrile controls (746 pg/mL, SD 551) (P < 0.001 and P = 0.001, respectively), but there was no difference in the IL-1RA between febrile episodes without FSs and febrile controls. CONCLUSIONS: Patients with FSs produce stronger inflammatory reactions during febrile episodes with FSs compared with febrile episodes without FSs and febrile controls. IMPACT: In patients with FSs, IL-1RA was higher following first FS than during febrile episodes without FSs and healthy periods after FSs. IL-1RA was higher in patients with FSs following first and recurrent FSs than in febrile controls. There was no significant difference in IL-1RA between febrile episodes of patients without FSs and febrile controls. Using IL-1RA as a surrogate marker of IL-1 axis activity, our results indicate that patients with FSs produced stronger inflammatory reactions during FS episodes but not during other febrile episodes or healthy periods after FSs. Cytokines may play a role in pathogenesis of FSs.

Effect of Topical Antibiotics on Duration of Acute Infective Conjunctivitis in Children: A Randomized Clinical Trial and a Systematic Review and Meta-analysis.

Importance: Although topical antibiotics are often prescribed for treating acute infective conjunctivitis in children, their efficacy is uncertain. Objective: To assess the efficacy of topical antibiotic therapy for acute infective conjunctivitis. Design, Setting, and Participants: A randomized clinical trial was conducted in primary health care in Oulu, Finland, from October 15, 2014, to February 7, 2020. Children aged 6 months to 7 years with acute infective conjunctivitis were eligible for enrollment. The participants were followed up for 14 days. A subsequent meta-analysis included the present trial and 3 previous randomized clinical trials enrolling pediatric patients aged 1 month to 18 years with acute infective conjunctivitis. Interventions: Participants in the present randomized clinical trial were randomized to moxifloxacin eye drops, placebo eye drops, or no intervention. Main Outcomes and Measures: The primary outcome in the present randomized clinical trial was time to clinical cure (in days); in the meta-analysis, the primary outcome was the proportion of participants with conjunctival symptoms on days 3 to 6. Results: The randomized clinical trial included 88 participants (46 [52%] girls), of whom 30 were randomized to moxifloxacin eye drops (mean [SD] age, 2.8 [1.6] years), 27 to placebo eye drops (mean [SD], age 3.0 [1.3] years), and 31 to no intervention (mean [SD] age, 3.2 [1.8] years). The time to clinical cure was significantly shorter in the moxifloxacin eye drop group than in the no intervention group (3.8 vs 5.7 days; difference, -1.9 days; 95% CI, -3.7 to -0.1 days; P = .04), while in the survival analysis both moxifloxacin and placebo eye drops significantly shortened the time to clinical cure relative to no intervention. In the meta-analysis, a total of 584 children were randomized (300 to topical antibiotics and 284 to a placebo), and the use of topical antibiotics was associated with a significant reduction in the proportion of children who had symptoms of conjunctivitis on days 3 to 6 compared with placebo eye drops (odds ratio, 0.59; 95% CI, 0.39 to 0.91). Conclusions and Relevance: In this randomized clinical trial and systematic review and meta-analysis, topical antibiotics were associated with significantly shorter durations of conjunctival symptoms in children with acute infective conjunctivitis. Trial Registration: ClinicalTrialsRegister.eu Identifier: 2013-005623-16.

Multi-inflammatory syndrome and Kawasaki disease in children during the COVID-19 pandemic: A nationwide register-based study and time series analysis.

AIM: We investigated whether the ongoing COVID-19 pandemic was associated with the occurrence of Kawasaki disease or with multi-inflammatory syndrome in children (MIS-C). METHODS: This national Finnish register-based study was based on laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, MIS-C and Kawasaki disease cases. We performed a time series analysis on the occurrence of Kawasaki disease in 2016-2020. RESULTS: In 2020, there were 5170 laboratory-confirmed COVID-19 cases in children under 18 years of age and five fulfilled the MIS-C case definition. The occurrence of MIS-C was 0.97 per 1000 (95% confidence interval: 0.31-2.26) laboratory-confirmed SARS-CoV-2 infections in children. Our time series analysis showed that Kawasaki disease cases decreased during the COVID-19 pandemic. The seasonally adjusted incidence rate ratio was 0.49 (95% confidence interval: 0.32-0.74) when it was compared to pre-pandemic levels. This coincided with a reduced occurrence of respiratory infections, due to social distancing in the population. CONCLUSION: This nationwide register-based study found that MIS-C was a rare complication of the SARS-CoV-2 infection. The occurrence of Kawasaki disease and respiratory infections decreased during the pandemic. This suggests that transmissible microbes may play an important role in Kawasaki disease and social distancing may have a protective effect.

Efficacy of the implementation of the National Emergency X-Radiography Utilization Study II decision rule to clinical practice for paediatric head injury patients.

AIM: To investigate the usefulness of the National Emergency X-Radiography Utilization Study (NEXUS) II head trauma decision rule in clinical practice for paediatric patients in a tertiary university hospital serving as the only paediatric hospital in the area. METHODS: We compared how doctors evaluated and examined patients with head injury during two time periods, before and after the introduction of NEXUS II decision rule. Multiple implementation strategies were used as follows: education, tutoring and written instructions for the use of NEXUS II. RESULTS: Two hundred and forty-four head injury patients visited the hospital before and 385 after the introduction of the NEXUS II decision rule. The number of hospital admissions (56%) and the mean duration of hospitalisation (2.5 days) remained the same during the two periods. In the NEXUS II evaluated group, there was a decrease of 40% in the number of hospital admissions. NEXUS II was applied in only 62 (16%) cases. The number of head imaging procedures remained the same. No patients with a clinically significant head injury were missed with the NEXUS II evaluation. CONCLUSION: NEXUS II was ineffective as our implementation failed. When used, NEXUS II reduced expenses in our study population by decreasing the number of hospital admissions.

Respiratory viruses and febrile response in children with febrile seizures: A cohort study and embedded case-control study.

OBJECTIVE: There are limited data on the pathogen-related and host-related factors in the pathogenesis of febrile seizures (FS). We designed a controlled study to compare the role of different respiratory viruses and febrile response in FS. METHODS: In a prospective cohort study of 1899 pediatric emergency room patients aged 6 months-6 years with a positive respiratory virus multiplex PCR, we identified 225 patients with FSs. We first compared the distribution of respiratory viruses in age-stratified patients with FSs with that in other patients. In an embedded case-control study, we compared the febrile response in patients with FSs with that in the controls matched for age, season and the same respiratory virus. RESULTS: The relative risk for FS was the highest for coronavirus OC43, 229E, and NL63 infections [RR: 3.2, 95 % confidence interval (CI): 1.4-7.2) and influenza A and B [RR: 2.5, 95 % CI: 1.4-4.7] as compared to those with other respiratory viral infections. The patients with FSs had a stronger febrile response of 39.2 °C (difference: 0.8 °C, 95 % CI: 0.5-1.2) later during hospitalization after acute care than the controls matched for the same respiratory virus. CONCLUSIONS: Influenza and coronaviruses caused relatively more FS-related emergency room visits than other respiratory viruses. Furthermore, the febrile response was stronger in the patients with FSs than in the controls matched for the same respiratory virus. The results suggest that the pathomechanism of FSs includes modifiable pathogen-related and host-related factors with possible potential in the prevention of FSs.

NIV NAVA versus Nasal CPAP in Premature Infants: A Randomized Clinical Trial.

BACKGROUND: Noninvasive ventilation is recommended for neonatal respiratory distress to avoid adverse effects of invasive ventilation. OBJECTIVE: The aim of this study was to compare the feasibility of noninvasive neurally adjusted ventilatory assist (NIV NAVA) and continuous positive airway pressure (CPAP) in preterm newborn infants. METHODS: Forty preterm infants (gestational age 28+0 to 36+6 weeks) requiring CPAP and supplemental oxygen (FiO2 >0.23) for respiratory distress at <48 h of postnatal age were randomized to NIV NAVA or CPAP. The primary endpoint was the inspired oxygen concentration 12 h after study inclusion. Secondary endpoints were the duration of oxygen treatment, total duration of respiratory support, parenteral nutrition, blood gas values, patient comfort, need for invasive ventilation, and treatment complications. RESULTS: The mean FiO2 at the time of study inclusion was 0.29 in both groups. After 12 h of treatment, FiO2 was 0.26 ± 0.07 and 0.26 ± 0.04 in the NIV NAVA and CPAP groups, respectively (difference 0.006, 95% CI -0.4 to 0.5), with no difference between the groups during the course of noninvasive ventilation (p = 0.80). Seven patients (35%) in the NIV NAVA group and 10 (50%) in the control group required intubation (difference 15%, 95% CI -15.5 to 4.3, p = 0.36). Time to intubation, gas exchange, vital parameters, pain scale, treatment complications, and neonatal outcome did not differ between the groups. CONCLUSIONS: In the present trial, NIV NAVA had no statistically significant effect on oxygen requirements or the need for invasive ventilation in preterm newborn infants.

Neurally adjusted ventilatory assist (NAVA) in preterm newborn infants with respiratory distress syndrome-a randomized controlled trial.

UNLABELLED: Neurally adjusted ventilatory assist (NAVA) improves patient-ventilator synchrony during invasive ventilation and leads to lower peak inspiratory pressures (PIP) and oxygen requirements. The aim of this trial was to compare NAVA with current standard ventilation in preterm infants in terms of the duration of invasive ventilation. Sixty infants born between 28 + 0 and 36 + 6 weeks of gestation and requiring invasive ventilation due to neonatal respiratory distress syndrome (RDS) were randomized to conventional ventilation or NAVA. The median durations of invasive ventilation were 34.7 h (quartiles 22.8-67.9 h) and 25.8 h (15.6-52.1 h) in the NAVA and control groups, respectively (P = 0.21). Lower PIPs were achieved with NAVA (P = 0.02), and the rapid reduction in PIP after changing the ventilation mode to NAVA made following the predetermined extubation criteria challenging. The other ventilatory and vital parameters did not differ between the groups. Frequent apneas and persistent pulmonary hypertension were conditions that limited the use of NAVA in 17 % of the patients randomized to the NAVA group. Similar cumulative doses of opiates were used in both groups (P = 0.71). CONCLUSIONS: NAVA was a safe and feasible ventilation mode for the majority of preterm infants suffering from RDS, but the traditional extubation criteria were not clinically applicable during NAVA. WHAT IS KNOWN: • NAVA improves patient-ventilator synchrony during invasive ventilation. • Lower airway pressures and oxygen requirements are achieved with NAVA during invasive ventilation in preterm infants by comparison with conventional ventilation. What is new: • Infants suffering from PPHN did not tolerate NAVA in the acute phase of their illness. • The traditional extubation criteria relying on inspiratory pressures and spontaneous breathing efforts were not clinically applicable during NAVA.