Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells.

Cellular senescence can exert dual effects in tumors, either suppressing or promoting tumor progression. The senescence-associated secretory phenotype (SASP), released by senescent cells, plays a crucial role in this dichotomy. Consequently, the clinical challenge lies in developing therapies that safely enhance senescence in cancer, favoring tumor-suppressive SASP factors over tumor-promoting ones. Here, we identify the retinoic-acid-receptor (RAR) agonist adapalene as an effective pro-senescence compound in prostate cancer (PCa). Reactivation of RARs triggers a robust senescence response and a tumor-suppressive SASP. In preclinical mouse models of PCa, the combination of adapalene and docetaxel promotes a tumor-suppressive SASP that enhances natural killer (NK) cell-mediated tumor clearance more effectively than either agent alone. This approach increases the efficacy of the allogenic infusion of human NK cells in mice injected with human PCa cells, suggesting an alternative therapeutic strategy to stimulate the anti-tumor immune response in "immunologically cold" tumors.

Disrupted Seasonality of Respiratory Viruses: Retrospective Analysis of Pediatric Hospitalizations in Italy from 2019 to 2023.

This multicenter study in Italian hospitals highlights the epidemiologic disruptions in the circulation of the 5 main respiratory viruses from 2019 to 2023. Our data reveal a resurgence of respiratory syncytial virus and influenza during the 2022-2023 winter season, with an earlier peak in cases for both viruses, emphasizing the importance of timely monitoring.

The mixed effect of Endocrine-Disrupting chemicals on biological age Acceleration: Unveiling the mechanism and potential intervention target.

INTRODUCTION: Although previous studies investigated the potential adverse effects of endocrine-disrupting chemicals (EDCs) on biological age acceleration and aging-related diseases, the mixed effect of multiple types of EDCs on biological age acceleration, including its potential underlying mechanism, remains unclear. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) were used to analyze biological age measures, including Klemera-Doubal method biological age (KDM-BA), phenotypic age, and homeostatic dysregulation (HD). Weight quantile sum (WQS) regression was performed to screen biological age-related EDCs (BA-EDCs) and assess the mixed effect of BA-EDCs on biological age acceleration and aging-related disease. Targets of BA-EDCs were obtained from three databases, while heart aging-related genes were obtained from the Aging Anno database. Protein-protein interaction (PPI) network and MCODE algorithm were applied to identify potential interactions between BA-EDC targets and heart aging-related genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to identify related pathways. RESULTS: This cross-sectional study included 1,439 participants. A decile increase in BA-EDCs co-exposure was associated with 0.31 years and 0.17 years of KDM-BA and phenotypic age acceleration, respectively. The mixed effect of BA-EDCs was associated with an increased prevalence of atherosclerotic cardiovascular disease (ASCVD). Vitamins C and E demonstrated a significant interaction effect on the association between BA-EDCs and KDM-BA acceleration. PPI network and functional enrichment analysis indicated that the AGE-RAGE signaling pathway in diabetic complications was significantly enriched. CONCLUSION: Our results showed that the co-exposure effect of BA-EDCs was associated with biological age acceleration and ASCVD, with the AGE-RAGE signaling pathway being the underlying mechanism. Vitamins C and E may also be an actionable target for preventing EDC-induced biological aging.

Nurturing the next generation of pediatric physician scientists: the Padova Physician Scientist Research Training for pediatric residents.

Less than 2% of physicians complete a research training (PhD) after the residency with a declining trend in those pursuing a clinical scientist pathway in pediatrics. The exposure to research methodology during the clinical training may play a role in engaging the next generations of pediatric physician scientist. Herein, we describe the experience of the Padova Physician Scientist Research Training (PPSRT) of the pediatric residency program at the University of Padova. The PPSRT was addressed to residents attending PGY2 to PGY4 of the pediatric program and consisted of two cores: a general one including in person or virtual lectures about research methodology in pediatrics including design of a clinical trial, writing of a scientific paper and statistical methods, and a subspecialties core for the discussion of research challenges in each area and the scientific writing activities. The perceived barriers to a research training and an evaluation of the program were assessed by an anonymized questionnaire. Sixty-four out 150 residents registered for the research training with 62/64 completing the two cores. The major perceived barrier to research during clinical training was the absence of protected time (89%) followed by the lack of specific funds (37%). The group activities lead to the publication of 24 papers.    Conclusion: This is the first experience in the Italian pediatric training of a dedicated research program within the frame of postgraduate medical education. Our report highlights the need for protected time to promote research interest and nurture a new generation of physician scientists. What is Known: • Training to medical research is not part of residency program. • The declining trend of physician scientists might be reverted by early exposure to research methodology and challenges during residency. What is New: • An early exposure to research training during pediatric residency increases the research engagement of pediatric residents. • The lack of protected time for research is perceived as the major barrier to research training during residency.

Mild Traumatic Brain Injury Characteristics and Symptoms in Preschool Children: How Do They Differ to School Age Children? A Multicenter Prospective Observational Study.

OBJECTIVE: To investigate if preschool children differ to school age children with mild traumatic brain injury (TBI) with respect to injury causes, clinical presentation, and medical management. DESIGN: A secondary analysis of a dataset from a large, prospective and multisite cohort study on TBI in children aged 0-18 years, the Australian Paediatric Head Injury Rules Study. SETTING: Nine pediatric emergency departments (ED) and 1 combined adult and pediatric ED located across Australia and New Zealand. PARTICIPANTS: 7080 preschool aged children (2-5 years) were compared with 5251 school-age children (6-12 years) with mild TBI (N= (N=12,331) MAIN OUTCOME MEASURES: Clinical report form on medical symptoms, injury causes, and management. RESULTS: Preschool children were less likely to be injured with a projectile than school age children (P<.001). Preschool children presented with less: loss of consciousness (P<.001), vomiting (P<.001), drowsiness (P=.002), and headache (P<.001), and more irritability and agitation (P=.003), than school-age children in the acute period after mild TBI. Preschool children were less likely to have neuroimaging of any kind (P<.001) or to be admitted for observation than school age children (P<.001). CONCLUSIONS: Our large prospective study has demonstrated that preschool children with mild TBI experience a different acute symptom profile to older children. There are significant clinical implications with symptoms post-TBI used in medical management to aid decisions on neuroimaging and post-acute intervention.

Fatigue recovery and connected factors following paediatric concussion.

OBJECTIVE: Using a biopsychosocial framework and the three-factor fatigue model, we aimed to (1) plot recovery of fatigue over the 3 months following paediatric concussion and (2) explore factors associated with persisting fatigue during the first 3 months postconcussion. METHODS: 240 children and adolescents aged 5-18 years (M=11.64, SD=3.16) completed assessments from time of injury to 3 months postinjury. Separate linear mixed effects models were conducted for child and parent ratings on the PedsQL-Multidimensional Fatigue Scale to plot recovery across domains (General, Cognitive, Sleep/Rest) and Total fatigue, from 1 week to 3 months postinjury. Two-block hierarchical regression analyses were then conducted for parent and child ratings of fatigue at each time point, with age, sex and acute symptoms in block 1 and child and parent mental health variables added to block 2. RESULTS: There was a significant reduction in both child and parent ratings across the 3 months postinjury for all fatigue domains (all p<0.001). For both child and parent fatigue ratings, child mental health was the most significant factor associated with fatigue at all time points. Adding child and parent mental health variables in the second block of the regression substantially increased the variance explained for both child and parent ratings of fatigue. CONCLUSION: Our findings confirm that fatigue improves during the first 3 months postconcussion and highlights the importance of considering child and parent mental health screening when assessing patients with persisting postconcussive symptoms.

Pediatric Sport-Related Concussion: Recommendations From the Amsterdam Consensus Statement 2023.

The 6th International Consensus Conference on Concussion in Sport, Amsterdam 2022, addressed sport-related concussion (SRC) in adults, adolescents, and children. We highlight the updated evidence-base and recommendations regarding SRC in children (5-12 years) and adolescents (13-18 years). Prevention strategies demonstrate lower SRC rates with mouthguard use, policy disallowing bodychecking in ice hockey, and neuromuscular training in adolescent rugby. The Sport Concussion Assessment Tools (SCAT) demonstrate robustness with the parent and child symptom scales, with the best diagnostic discrimination within the first 72 hours postinjury. Subacute evaluation (>72 hours) requires a multimodal tool incorporating symptom scales, balance measures, cognitive, oculomotor and vestibular, mental health, and sleep assessment, to which end the Sport Concussion Office Assessment Tools (SCOAT6 [13+] and Child SCOAT6 [8-12]) were developed. Rather than strict rest, early return to light physical activity and reduced screen time facilitate recovery. Cervicovestibular rehabilitation is recommended for adolescents with dizziness, neck pain, and/or headaches for greater than 10 days. Active rehabilitation and collaborative care for adolescents with persisting symptoms for more than 30 days may decrease symptoms. No tests and measures other than standardized and validated symptom rating scales are valid for diagnosing persisting symptoms after concussion. Fluid and imaging biomarkers currently have limited clinical utility in diagnosing or assessing recovery from SRC. Improved paradigms for return to school were developed. The variable nature of disability and differences in evaluating para athletes and those of diverse ethnicity, sex, and gender are discussed, as are ethical considerations and future directions in pediatric SRC research.

SIMPEDVR: using VR in teaching pediatric emergencies to undergraduate students-a pilot study.

The objective of this work was to provide pilot data on feasibility of using virtual reality (VR) to train undergraduate students in pediatric emergency scenarios. We staged VR sessions for a total of 45 medical and nursing students; in every session, each student managed two pediatric emergency virtual scenarios. At the end of the sessions, students completed a Technology Assessment Questionnaire to evaluate the perceived usefulness and perceived ease-of-use of their VR training experience and rated their perceived level of competence in managing the two clinical scenarios. The median perceived usefulness was 91.7/100 (interquartile range (IQR) 80.6-100), while the median perceived ease-of-use was 77.8/100 (IQR 63.9-88.9). The perceived level of competence increased from 2 (IQR 1-3) to 4 (IQR 3-4) on a 5-point Likert scale, for both scenarios (p < 0.001, Wilcoxon test for paired samples).       Conclusions: The staged VR sessions had a good perceived usefulness and resulted in an increase in the perceived level of competence. The results on the ease-of-use, however, show that an assumption that millennials and younger students can navigate with confidence VR hardware in a healthcare training setting should not be made; further work is required to ease the integration of VR into curricula. What is Known: • Virtual reality (VR) is a rising simulation training methodology in Pediatric Emergency Medicine (PEM), however little experience is reported about its use for undergraduate students What is New: • VR PEM trainiing was found useful by undergraduate students and its use increased their perceived level of competence, although ease-of-use received lower ratings. • Despite the young age, an assumption that millennials and younger students can navigate with confidence VR hardware in a healthcare training setting should not be made.

A SuperLearner-enforced approach for the estimation of treatment effect in pediatric trials.

Background: Randomized Clinical Trials (RCT) represent the gold standard among scientific evidence. RCTs are tailored to control selection bias and the confounding effect of baseline characteristics on the effect of treatment. However, trial conduction and enrolment procedures could be challenging, especially for rare diseases and paediatric research. In these research frameworks, the treatment effect estimation could be compromised. A potential countermeasure is to develop predictive models on the probability of the baseline disease based on previously collected observational data. Machine learning (ML) algorithms have recently become attractive in clinical research because of their flexibility and improved performance compared to standard statistical methods in developing predictive models. Objective: This manuscript proposes an ML-enforced treatment effect estimation procedure based on an ensemble SuperLearner (SL) approach, trained on historical observational data, to control the confounding effect. Methods: The REnal SCarring Urinary infEction trial served as a motivating example. Historical observational study data have been simulated through 10,000 Monte Carlo (MC) runs. Hypothetical RCTs have been also simulated, for each MC run, assuming different treatment effects of antibiotics combined with steroids. For each MC simulation, the SL tool has been applied to the simulated observational data. Furthermore, the average treatment effect (ATE), has been estimated on the trial data and adjusted for the SL predicted probability of renal scar. Results: The simulation results revealed an increased power in ATE estimation for the SL-enforced estimation compared to the unadjusted estimates for all the algorithms composing the ensemble SL.

Effectiveness of a Novel Tablet Application in Reducing Guideline Deviations During Pediatric Cardiac Arrest: A Randomized Clinical Trial.

Importance: Deviations from international resuscitation guidelines during the management of pediatric cardiac arrest are frequent and affect clinical outcomes. An interactive tablet application (app), PediAppRREST, was developed to reduce guideline deviations during pediatric cardiac arrest. Objective: To assess the effectiveness of PediAppRREST in improving the management of simulated in-hospital pediatric cardiac arrest. Design, Setting, and Participants: This multicenter 3-group simulation-based randomized clinical trial was conducted from September 2020 to December 2021 at 4 Italian university hospitals (Padua, Florence, Rome, Novara). Participants included residents in pediatrics, emergency medicine, and anesthesiology. Analyses were conducted as intention-to-treat. Data were analyzed from January to June 2022. Interventions: Teams were randomized to 1 of 3 study groups: an intervention group that used the PediAppRREST app; a control group that used a paper-based cognitive aid, the Pediatric Advanced Life Support (PALS) pocket card; and a control group that used no cognitive aids. All the teams managed the same standardized simulated scenario of nonshockable pediatric cardiac arrest. Main Outcomes and Measures: The primary outcome was the number of deviations from guidelines, measured by a 15-item checklist based on guideline recommendations. The main secondary outcomes were quality of chest compressions, team clinical performance (measured by the Clinical Performance Tool), and perceived team leader's workload. Study outcomes were assessed via video reviews of the scenarios. Results: Overall 100 teams of 300 participants (mean [SD] age, 29.0 [2.2] years; 195 [65%] female) were analyzed by intention-to-treat, including 32 teams randomized to the PediAppRREST group, 35 teams randomized to the PALS control group, and 33 teams randomized to the null control group. Participant characteristics (210 pediatric residents [70%]; 48 anesthesiology residents [16%]; 42 emergency medicine residents [14%]) were not statistically different among the study groups. The number of deviations from guidelines was significantly lower in the PediAppRREST group than in the control groups (mean difference vs PALS control, -3.0; 95% CI, -4.0 to -1.9; P < .001; mean difference vs null control, -2.6; 95% CI, -3.6 to -1.5; P < .001). Clinical Performance Tool scores were significantly higher in the PediAppRREST group than control groups (mean difference vs PALS control, 1.4; 95% CI, 0.4 to 2.3; P = .002; mean difference vs null control, 1.1; 95% CI, 0.2 to 2.1; P = .01). The other secondary outcomes did not significantly differ among the study groups. Conclusions and Relevance: In this randomized clinical trial, the use of the PediAppRREST app resulted in fewer deviations from guidelines and a better team clinical performance during the management of pediatric cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT04619498.

Pediatric Injury Surveillance From Uncoded Emergency Department Admission Records in Italy: Machine Learning-Based Text-Mining Approach.

BACKGROUND: Unintentional injury is the leading cause of death in young children. Emergency department (ED) diagnoses are a useful source of information for injury epidemiological surveillance purposes. However, ED data collection systems often use free-text fields to report patient diagnoses. Machine learning techniques (MLTs) are powerful tools for automatic text classification. The MLT system is useful to improve injury surveillance by speeding up the manual free-text coding tasks of ED diagnoses. OBJECTIVE: This research aims to develop a tool for automatic free-text classification of ED diagnoses to automatically identify injury cases. The automatic classification system also serves for epidemiological purposes to identify the burden of pediatric injuries in Padua, a large province in the Veneto region in the Northeast Italy. METHODS: The study includes 283,468 pediatric admissions between 2007 and 2018 to the Padova University Hospital ED, a large referral center in Northern Italy. Each record reports a diagnosis by free text. The records are standard tools for reporting patient diagnoses. An expert pediatrician manually classified a randomly extracted sample of approximately 40,000 diagnoses. This study sample served as the gold standard to train an MLT classifier. After preprocessing, a document-term matrix was created. The machine learning classifiers, including decision tree, random forest, gradient boosting method (GBM), and support vector machine (SVM), were tuned by 4-fold cross-validation. The injury diagnoses were classified into 3 hierarchical classification tasks, as follows: injury versus noninjury (task A), intentional versus unintentional injury (task B), and type of unintentional injury (task C), according to the World Health Organization classification of injuries. RESULTS: The SVM classifier achieved the highest performance accuracy (94.14%) in classifying injury versus noninjury cases (task A). The GBM method produced the best results (92% accuracy) for the unintentional and intentional injury classification task (task B). The highest accuracy for the unintentional injury subclassification (task C) was achieved by the SVM classifier. The SVM, random forest, and GBM algorithms performed similarly against the gold standard across different tasks. CONCLUSIONS: This study shows that MLTs are promising techniques for improving epidemiological surveillance, allowing for the automatic classification of pediatric ED free-text diagnoses. The MLTs revealed a suitable classification performance, especially for general injuries and intentional injury classification. This automatic classification could facilitate the epidemiological surveillance of pediatric injuries by also reducing the health professionals' efforts in manually classifying diagnoses for research purposes.

Role of biomarkers and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion: a systematic review.

OBJECTIVE: Determine the role of fluid-based biomarkers, advanced neuroimaging, genetic testing and emerging technologies in defining and assessing neurobiological recovery after sport-related concussion (SRC). DESIGN: Systematic review. DATA SOURCES: Searches of seven databases from 1 January 2001 through 24 March 2022 using keywords and index terms relevant to concussion, sports and neurobiological recovery. Separate reviews were conducted for studies involving neuroimaging, fluid biomarkers, genetic testing and emerging technologies. A standardised method and data extraction tool was used to document the study design, population, methodology and results. Reviewers also rated the risk of bias and quality of each study. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they: (1) were published in English; (2) represented original research; (3) involved human research; (4) pertained only to SRC; (5) included data involving neuroimaging (including electrophysiological testing), fluid biomarkers or genetic testing or other advanced technologies used to assess neurobiological recovery after SRC; (6) had a minimum of one data collection point within 6 months post-SRC; and (7) contained a minimum sample size of 10 participants. RESULTS: A total of 205 studies met inclusion criteria, including 81 neuroimaging, 50 fluid biomarkers, 5 genetic testing, 73 advanced technologies studies (4 studies overlapped two separate domains). Numerous studies have demonstrated the ability of neuroimaging and fluid-based biomarkers to detect the acute effects of concussion and to track neurobiological recovery after injury. Recent studies have also reported on the diagnostic and prognostic performance of emerging technologies in the assessment of SRC. In sum, the available evidence reinforces the theory that physiological recovery may persist beyond clinical recovery after SRC. The potential role of genetic testing remains unclear based on limited research. CONCLUSIONS: Advanced neuroimaging, fluid-based biomarkers, genetic testing and emerging technologies are valuable research tools for the study of SRC, but there is not sufficient evidence to recommend their use in clinical practice. PROSPERO REGISTRATION NUMBER: CRD42020164558.

Concussion Knowledge and Self-Reported Behaviors in Youth Rugby Players and Their Coaches: A Population-Wide Cross-Sectional Survey.

OBJECTIVE: To investigate concussion knowledge and self-reported behaviors in Italian youth rugby players and their coaches. To investigate predictors of lower concussion knowledge and association between athletes' self-reported knowledge and behavior. DESIGN: Cross-sectional, population-wide, survey study. SETTING: All rugby clubs (n = 52) of the Veneto region (Italy). PARTICIPANTS: Players and coaches of all under 15, 17 and 19 teams. Overall, 1719 athlete surveys (92.2% male; response rate, 71.1%) and 235 coach surveys (93.6% male; response rate, 93.2%) were eligible for analysis. INTERVENTION: Surveys circulated from September 20 to December 13, 2021. MAIN OUTCOME MEASURES: Knowledge scores were reported as a percentage of correct answers. Descriptive statistics were reported for all answers. The primary outcomes were concussion knowledge and self-reported behaviors. The secondary outcomes were the association between knowledge and participant individual factors and self-reported behaviors. RESULTS: Median knowledge score for athletes was 55% (IQR: 44-67) and for coaches was 60% (IQR: 52.5-69). Only 33.3% of athletes and 40% of coaches were aware of an increased risk of a second concussion after sustaining one. Athletes who had never heard of the word concussion (effect: -9.31; SE: 1.35, 95% CI: -12.0 to -6.7; P < 0.0001) and coaches with longer coaching experience (effect: -4.35; SE: 2.0, 95% CI: -8.29 to -0.41; P < 0.03) reported lower knowledge scores. There was no statistical association between knowledge scores and athlete self-reported behavior. CONCLUSION: Athletes and coaches had a similar level of concussion knowledge. Knowledge score of athletes did not predict self-reported behaviors. Although enhanced concussion education should be undertaken, interventions to ensure appropriate concussion reporting behaviors are also required.

Parental help-seeking behaviour for, and care of, a sick or injured child during the COVID-19 pandemic: a European online survey.

BACKGROUND: Globally, the COVID-19 pandemic had a huge impact on patients and healthcare systems. A decline in paediatric visits to healthcare settings was observed, which might have been due to lower incidence of injury and infectious illness, changes in healthcare services and parental concern. The aim of our study was to examine parental experiences of help-seeking for, and care of, a sick or injured child during COVID-19 lockdown periods in five European countries with different healthcare systems in place. METHODS: An online survey for parents with a child with any kind or illness of injury during COVID-19 lockdowns was circulated through social media in five European countries: Italy, Spain, Sweden, the Netherlands, and the United Kingdom. Parents living in one of these countries with self-identification of a sick or injured child during COVID-19 lockdown periods were eligible to fill in the survey. Descriptive statistics were used for the level of restrictions per country, children's characteristics, family characteristics and reported help-seeking behaviour of parents prior to the lockdown and their real experience during the lockdown. The free text data was subjected to thematic analysis. RESULTS: The survey was fully completed by 598 parents, ranging from 50 to 198 parents per country, during varying lockdown periods from March 2020 until May 2022. Parents who completed the survey were not deterred from seeking medical help for their sick or injured child during the COVID-19 pandemic. This finding was comparable in five European countries with different healthcare systems in place. Thematic analysis identified three main areas: parental experiences of access to healthcare, changes in parents' help-seeking behaviours for a sick or injured child during lockdowns, and the impact of caring for a sick or injured child during the lockdowns. Parents reported limited access to non-urgent care services and were anxious about either their child or themselves catching COVID-19. CONCLUSION: This insight into parental perspectives of help-seeking behaviour and care for a sick or injured child during COVID-19 lockdowns could inform future strategies to improve access to healthcare, and to provide parents with adequate information concerning when and where to seek help and support during pandemics.

Cerebral blood flow in children with persisting postconcussive symptoms and posttraumatic headache at 2 weeks postconcussion.

OBJECTIVE: Persisting postconcussive symptoms (pPCS), particularly headache, can significantly disrupt children's recovery and functioning. However, the underlying pathophysiology of these symptoms remains unclear. The goal in this study was to determine whether pPCS are related to cerebral blood flow (CBF) at 2 weeks postconcussion. The authors also investigated whether variations in CBF can explain the increased risk of acute posttraumatic headache (PTH) in female children following concussion. METHODS: As part of a prospective, longitudinal study, the authors recruited children 5-18 years old who were admitted to the emergency department of a tertiary pediatric hospital with a concussion sustained within 48 hours of admission. Participants underwent pseudocontinuous arterial spin labeling MRI at 2 weeks postconcussion to quantify global mean gray and white matter perfusion (in ml/100 g/min). Conventional frequentist analysis and Bayesian analysis were performed. RESULTS: Comparison of recovered (n = 26) and symptomatic (n = 12) groups (mean age 13.15 years, SD 2.69 years; 28 male) found no differences in mean global gray and white matter perfusion at 2 weeks postconcussion (Bayes factors > 3). Although female sex was identified as a risk factor for PTH with migraine features (p = 0.003), there was no difference in CBF between female children with and without PTH. CONCLUSIONS: Global CBF was not associated with pPCS and female PTH at 2 weeks after pediatric concussion. These findings provide evidence against the use of CBF measured by arterial spin labeling as an acute biomarker for pediatric concussion recovery.

"Procedural sedation and analgesia in Italian pediatric emergency departments: a subgroup analysis in italian hospitals".

To date, pain and anxiety are the most common symptoms reported by children who refer to pediatric emergency department. Despite it is well known that the undertreatment of this condition has some negative consequences in a short term and long term of time, gaps in the management of pain in this setting still persist. This subgroup analysis aims to describe the current state of art of pediatric sedation and analgesia in Italian emergency departments and to identify existing gaps to solve. This is a subgroup analysis of a cross-sectional European survey of pediatric emergency departments sedation and analgesia practice undertaken between November 2019 and March 2020. The survey proposed a case vignette and questions addressing several domains, like the management of pain, availability of medications, protocols and safety aspects, staff training and availability of human resources around procedural sedation and analgesia. Italian sites responding to the survey were identified and their data were isolated and checked for completeness. Eighteen Italian sites participated to the study, the 66% of which was represented University Hospitals and/or Tertiary Care Centers. The most concerning results were an inadequate sedation to 27% of patients, lack of availability of certain medications like nitrous oxide, the lack of use of intranasal fentanyl and topical anesthetics at the triage, the rare use of safety protocols and preprocedural checklists, lack of staff training and lack of space. Furthermore, the unavailability of Child Life Specialists and hypnosis emerged. Despite procedural sedation and analgesia in Italian pediatric emergency departments is progressively more used than previously, several aspects still require an implementation. Our subgroup analysis could be a starter point for further studies and to improve and make the current Italian recommendations more homogeneous.

Incidence of traumatic brain injuries in head-injured children with seizures.

OBJECTIVE: Incidence and short-term outcomes of clinically important traumatic brain injury (ciTBI) in head-injured children presenting to ED with post-traumatic seizure (PTS) is not described in current literature. METHODS: Planned secondary analysis of a prospective observational study undertaken in 10 Australasian Paediatric Research in Emergency Departments International Collaborative (PREDICT) network EDs between 2011 and 2014 of head-injured children <18 years with and without PTS. Clinical predictors and outcomes were analysed by attributable risk (AR), risk ratios (RR) and 95% confidence interval (CI), including the association with Glasgow Coma Scale (GCS) scores. RESULTS: Of 20 137 head injuries, 336 (1.7%) had PTS with median age of 4.8 years. Initial GCS was 15 in 268/336 (79.8%, AR -16.1 [95% CI -20.4 to -11.8]), 14 in 24/336 (7.1%, AR 4.4 [95% CI 1.6-7.2]) and ≤13 in 44/336 (13.1%, AR 11.7 [95% CI 8.1-15.3]) in comparison with those without PTS, respectively. The ciTBI rate was 34 (10.1%) with PTS versus 219 (1.1%) without PTS (AR 9.0 [95% CI 5.8-12.2]) with 5/268 (1.9%), 6/24 (25.0%) and 23/44 (52.3%) with GCS 15, 14 and ≤13, respectively. In PTS, rates of admission ≥2 nights (34 [10.1%] AR 9.0 [95% CI 5.8-12.3]), intubation >24 h (9 [2.7%] AR 2.5 [95% CI 0.8-4.2]) and neurosurgery (8 [2.4%] AR 2.0 [95% CI 0.4-3.7]), were higher than those without PTS. Children with PTS and GCS 15 or 14 had no neurosurgery, intubations or death, with two deaths in children with PTS and GCS ≤13. CONCLUSIONS: PTS was uncommon in head-injured children presenting to the ED but associated with an increased risk of ciTBI in those with reduced GCS on arrival.

Respective roles of non-pharmaceutical interventions in bronchiolitis outbreaks: an interrupted time-series analysis based on a multinational surveillance system.

BACKGROUND: Bronchiolitis is a major source of morbimortality among young children worldwide. Non-pharmaceutical interventions (NPIs) implemented to reduce the spread of severe acute respiratory syndrome coronavirus 2 may have had an important impact on bronchiolitis outbreaks, as well as major societal consequences. Discriminating between their respective impacts would help define optimal public health strategies against bronchiolitis. We aimed to assess the respective impact of each NPI on bronchiolitis outbreaks in 14 European countries. METHODS: We conducted a quasi-experimental interrupted time-series analysis based on a multicentre international study. All children diagnosed with bronchiolitis presenting to the paediatric emergency department of one of 27 centres from January 2018 to March 2021 were included. We assessed the association between each NPI and change in the bronchiolitis trend over time by seasonally adjusted multivariable quasi-Poisson regression modelling. RESULTS: In total, 42 916 children were included. We observed an overall cumulative 78% (95% CI -100- -54%; p<0.0001) reduction in bronchiolitis cases following NPI implementation. The decrease varied between countries from -97% (95% CI -100- -47%; p=0.0005) to -36% (95% CI -79-7%; p=0.105). Full lockdown (incidence rate ratio (IRR) 0.21 (95% CI 0.14-0.30); p<0.001), secondary school closure (IRR 0.33 (95% CI 0.20-0.52); p<0.0001), wearing a mask indoors (IRR 0.49 (95% CI 0.25-0.94); p=0.034) and teleworking (IRR 0.55 (95% CI 0.31-0.97); p=0.038) were independently associated with reducing bronchiolitis. CONCLUSIONS: Several NPIs were associated with a reduction of bronchiolitis outbreaks, including full lockdown, school closure, teleworking and facial masking. Some of these public health interventions may be considered to further reduce the global burden of bronchiolitis.