Validation of Administrative Data and Timing of Point Prevalence Surveys for Antibiotic Monitoring.

Importance: Point prevalence surveys (PPSs) are used globally to collect data on antibiotic prescriptions. However, the optimal frequency for data collection to ensure comprehensive understanding of antibiotic use and to target and monitor stewardship interventions remains unknown. Objective: To identify the optimal frequency for collecting data on antibiotic use among the pediatric population through PPSs leveraging administrative data. Design, Setting, and Participants: This prognostic study used a cross-sectional validation approach and was conducted in pediatric outpatient and inpatient settings in the Veneto region of Italy. Antibiotics were classified according to the World Health Organization Access, Watch and Reserve criteria. Prescribing rates of access antibiotics were analyzed for pediatric inpatients with records dated between October 1, 2014, and December 31, 2022, and outpatients with records dated between January 1, 2010, and December 31, 2022. The study included children younger than 15 years with an antibiotic prescription who were admitted to the pediatric acute care unit or evaluated by a primary care pediatrician. Data analysis was performed from October 2023 to January 2024. Main Outcomes and Measures: An algorithm was developed to identify optimal time frames for conducting PPSs. This approach sought to minimize the discrepancy between quarterly and yearly PPS results, aiming to accurately estimate annual antibiotic prescribing rates in both inpatient and outpatient settings (primary outcome). External validity of the optimal PPS time frames derived from outpatient data when applied to the inpatient setting was also investigated. Validation involved assessing the effectiveness of administrative data in identifying strategic PPS periods for capturing inpatient antibiotic use patterns (secondary outcome). Results: This analysis included 106 309 children: 3124 were inpatients (1773 males [56.8%]) and 103 185 were outpatients (53 651 males [52.0%]). A total of 5099 and 474 867 antibiotic prescriptions from inpatients and outpatients were analyzed, respectively. Outpatients tended to be older than inpatients, with a median age of 3.2 (IQR, 1.3-6.3) years vs 2.6 (IQR, 0.6-6.6) years, respectively, and with a lower burden of clinical comorbidities (≥1 comorbidity: 6618 [6.4%] vs 1141 [36.5%], respectively). The algorithm successfully identified distinct time frames within the calendar year from inpatient and outpatient records optimized for PPS data collection. Rates obtained from the quarterly PPS during these identified periods exhibited greater agreement with annual antibiotic prescribing rates (inpatient: r = 0.17, P < .001; and outpatient: r = 0.42, P < .001) than those derived from the yearly PPS (inpatient: r = 0.04, P = .58; and outpatient: r = 0.05, P = .34), with a Δ reduction of up to 89.8% (where Δ represents the percentage point change in antibiotic prescribing rates). Furthermore, the optimal PPS time frames gleaned from the outpatient data demonstrated robust applicability to the inpatient setting, yielding comparable results in both scenarios. Conclusions and Relevance: This study evaluated the potential of administrative data in determining the optimal timing of PPS implementation. The quarterly PPS balanced precision and sustainability, especially when implemented during strategically selected periods across different seasons. Further studies are needed to validate the algorithm used in this study, especially in post-COVID-19 pandemic years and different settings.

Coagulation factor X promotes resistance to androgen-deprivation therapy in prostate cancer.

Although hypercoagulability is commonly associated with malignancies, whether coagulation factors directly affect tumor cell proliferation remains unclear. Herein, by performing single-cell RNA sequencing (scRNA-seq) of the prostate tumor microenvironment (TME) of mouse models of castration-resistant prostate cancer (CRPC), we report that immunosuppressive neutrophils (PMN-MDSCs) are a key extra-hepatic source of coagulation factor X (FX). FX activation within the TME enhances androgen-independent tumor growth by activating the protease-activated receptor 2 (PAR2) and the phosphorylation of ERK1/2 in tumor cells. Genetic and pharmacological inhibition of factor Xa (FXa) antagonizes the oncogenic activity of PMN-MDSCs, reduces tumor progression, and synergizes with enzalutamide therapy. Intriguingly, F10high PMN-MDSCs express the surface marker CD84 and CD84 ligation enhances F10 expression. Elevated levels of FX, CD84, and PAR2 in prostate tumors associate with worse survival in CRPC patients. This study provides evidence that FXa directly promotes cancer and highlights additional targets for PMN-MDSCs for cancer therapies.

Implementation of the WHO standards to assess the quality of care for children with acute diarrhoea: findings of a multicentre study (CHOICE) in Italy.

BACKGROUND: There is no documented experience in the use of the WHO standards for improving the quality of care (QOC) for children at the facility level. We describe the use of 10 prioritised WHO-Standard-based Quality Measures to assess QOC for children with acute diarrhoea (AD) in Italy. METHODS: In a multicentre observational study in 11 paediatric emergency departments with different characteristics and geographical location, we collected data on 3061 children aged 6 months to 15 years with AD and no complications. Univariate and multivariate analyses were conducted. RESULTS: Study findings highlighted both good practices and gaps in QoC, with major differences in QOC across facilities. Documentation of body weight and temperature varied from 7.7% to 98.5% and from 50% to 97.7%, respectively (p<0.001); antibiotic and probiotic prescription rates ranged from 0% to 10.1% and from 0% to 80.8%, respectively (p<0.001); hospitalisations rates ranged between 8.5% and 62.8% (p<0.001); written indications for reassessment were provided in 10.4%-90.2% of cases (p<0.001). When corrected for children's individual characteristics, the variable more consistently associated with each analysed outcome was the individual facility. Higher rates of antibiotics prescription (+7.6%, p=0.04) and hospitalisation (+52.9%, p<0.001) were observed for facilities in Southern Italy, compared with university centres (-36%, p<0.001), independently from children characteristics. Children's clinical characteristics in each centre were not associated with either hospitalisation or antibiotic prescription rates. CONCLUSIONS: The 10 prioritised WHO-Standard-based Quality Measures allow a rapid assessment of QOC in children with AD. Action is needed to identify and implement sustainable and effective interventions to ensure high QOC for all children.

Implementation of the WHO standards to assess quality of care for children with acute pain in EDs: findings of a multicentre study (CHOICE) in Italy.

BACKGROUND: There is little experience on the use of the WHO Standards for improving the quality of care (QOC) for children. We describe the use of four prioritised WHO Standard-based Quality Measures to assess the provision of care for children with pain in emergency departments (EDs). METHODS: In a multicentre observational study in 10 EDs with different characteristics in Italy, we collected data on 3355 children accessing the EDs between January 2019 and December 2020. The association between children and facility characteristics and quality measures was analysed through multivariate analyses. RESULTS: The proportion of children whose pain was measured was 68.7% (n=2305), with extreme variations across different centres (from 0.0% to 99.8%, p<0.001). The proportion of children treated for pain was 28.9% (n=970) again with a wide range (5.3%-56.3%, p<0.001). The difference between the frequency of children with pain measured and pain treated varied widely between the facilities (ranging from -24.3 to 82). Children with moderate and severe pain were more frequently treated (48.9% and 62.9% of cases, respectively), although with large variations across centres (ranges: 0%-74.8% and 0%-100% respectively, p<0.001). After correction for children's characteristics, the variable more strongly associated with analysed outcomes was the facility which the child accessed for care. Being a facility in Northern Italy was associated with a higher rate of pain measurement (67.3%-95% CI: 39.9% to 94.6%, p<0.001) compared with facilities in South Italy (-22.1% lower (95% CI: -41.7% to -2.50%, p=0.03). CONCLUSIONS: The use of few WHO Standard-based measures related to pain can help identifying priority gaps in QOC for children and in monitoring it over time. There is a need for more implementation research to establish which are the most sustainable and effective interventions to improve the QOC for acute pain in children.

Implementation of the WHO Standards to assess quality of paediatric care at the facility level using service users' perspective as source of data: a multicentre quality improvement study in Italy.

OBJECTIVES: There is little experience in the use of the WHO Standards for improving the quality of care (QOC) for children at the facility level. We describe the use of 75 WHO Standard based Quality Measures to assess paediatric QOC, using service users as a source of data, in Italy. STUDY DESIGN: In a cross-sectional study including 12 hospitals, parents/caregivers of admitted children completed a validated questionnaire including 75 Quality Measures: 40 pertinent to the domain of experience of care; 25 to physical/structural resources; 10 to COVID-19 reorganisational changes. Univariate and multivariate analyses were conducted. RESULTS: Answers from 1482 service users were analysed. Physical resources was the domain with the higher frequency of reported gaps in QOC, with key gaps (higher rates of responders reporting need for improvement and low variability across centres) being: (1) quality of meals (48.1%; range across facilities: 35.3%-61.7%); (2) presence of cooking areas (50.9%; range: 34.6%-70.0%); (3) spaces for family/friends (51.3%; range: 31.8%-77.4%). For experience of care, the most critical gap was the information on the rights of the child (76.6%; range: 59.9%-90.4%), with most other Quality Measures showing an overall frequency of reported need for improvement ranging between 5% and 35%. For reorganisational changes due to COVID-19 an improvement was felt necessary by <25% of responders in all Quality Measures, with low variability across centres. At the multivariate analyses, factors significantly associated with the QOC Index largely varied by QOC domain. CONCLUSIONS: The use of the 75 prioritised Quality Measures, specific to service users' perspective, enabled the identification of both general and facility-specific gaps in QOC. Based on these findings, quality improvement initiatives shall focus on a core list of selected Quality Measures common to all facilities, plus on an additional list of Quality Measures as more relevant in each facility.

Evaluation of the WHO standards to assess quality of care for children with acute respiratory infections: findings of a baseline multicentre assessment (CHOICE) in Italy.

BACKGROUND: Experience is lacking on the implementation of the WHO standards for improving the quality of care (QOC) for children at facility level. We describe the use of 10 prioritised WHO standard-based quality measures to assess provision of care for children with acute respiratory infections (ARI) in Italy. METHODS: In a multicentre observational study across 11 emergency departments with different characteristics, we collected 10 WHO standard-based quality measures related to case management of children with ARI and no emergency/priority signs. Univariate and multivariate analyses were conducted. RESULTS: Data from 3145 children were collected. Major differences in QOC across facilities were observed: documentation of saturation level and respiratory rate varied from 34.3% to 100% and from 10.7% to 62.7%, respectively (p<0.001); antibiotic prescription rates ranged from 22.6% to 80.0% (p<0.001), with significant differences in the pattern of prescribed antibiotic; hospitalisations rates ranged between 2.3% and 30.6% (p<0.001). When corrected for children's individual sociodemographic and clinical characteristics, the variable more consistently associated with each analysed outcome was the individual facility where the child was managed. Higher rates of antibiotics prescription (+33.1%, p<0.001) and hospitalisation (+24.7%, p<0.001) were observed for facilities in Southern Italy, while university centres were associated with lower hospitalisation rates (-13.1%, p<0.001), independently from children's characteristics. CONCLUSIONS: The use of 10 WHO standard-based measures can help quickly assess QOC for children with ARI. There is an urgent need to invest more in implementation research to identify sustainable and effective interventions to ensure that all children receive high QOC.

Severe and invasive bacterial infections in infants aged less than 90 days with and without SARS-CoV-2 infection.

BACKGROUND: Fever in children represents one of the most common causes of medical evaluation. Infants younger than 90 days of age are at higher risk of severe and invasive bacterial infections (SBI and IBI). However, clinical signs and symptoms of viral and bacterial infections in young infants are frequently similar, and several studies have shown that the risk of SBIs remains non-negligible even in the presence of a positive point-of-care viral test. Our study aims to evaluate whether the proportion of SBIs and IBIs in febrile infants younger than 90 days during the COVID-19 pandemic was higher than that in the pre-pandemic period, and to describe the proportion of SBIs and IBIs in infants with and without SARS-CoV-2 infection. METHODS: This was a retrospective single-center cohort study conducted at the Children's Hospital of the University of Padua in Italy, involving febrile young infants evaluated in the Pediatric Emergency Department (PED) and admitted to Pediatric Acute Care Unit (PACU) between March 2017 to December 2022. Infants admitted before the COVID-19 pandemic were compared to infants admitted during the pandemic period and SARS-CoV-2 positive patients to the negative ones. RESULTS: 442 febrile infants younger than 90 days were evaluated in Padua PED and admitted to the wards. The proportion of SBIs and IBIS did not significantly change over the study periods, ranging between 10.8% and 32.6% (p = 0.117) and between 0% and 7.6%, respectively (p = 0.367). The proportion of infants with a diagnosis of SBIs and IBIs was higher in the SARS-CoV-2 negative group (30.3% and 8.2%, respectively) compared to the positive group (8.5% and 2.8%, respectively) (p < 0.0001). The most common diagnosis in both groups was UTI, mainly caused by E. coli. A similar proportion of blood and urine cultures were performed, whereas lumbar puncture was more frequently performed in SARS-CoV-2 negative infants (40.2% vs 16.9%, p = 0.001). CONCLUSIONS: Although the risk of concomitant serious bacterial infection with SARS-CoV-2 is low, it remains non-negligible. Therefore, even in SARS-CoV-2-positive febrile infants, we suggest that the approach to screening for SBIs remains cautious.

Targeting senescence induced by age or chemotherapy with a polyphenol-rich natural extract improves longevity and healthspan in mice.

Accumulating senescent cells within tissues contribute to the progression of aging and age-related diseases. Botanical extracts, rich in phytoconstituents, present a useful resource for discovering therapies that could target senescence and thus improve healthspan. Here, we show that daily oral administration of a standardized extract of Salvia haenkei (Haenkenium (HK)) extended lifespan and healthspan of naturally aged mice. HK treatment inhibited age-induced inflammation, fibrosis and senescence markers across several tissues, as well as increased muscle strength and fur thickness compared with age-matched controls. We also found that HK treatment reduced acutely induced senescence by the chemotherapeutic agent doxorubicin, using p16LUC reporter mice. We profiled the constituent components of HK by mass spectrometry, and identified luteolin-the most concentrated flavonoid in HK-as a senomorphic compound. Mechanistically, by performing surface plasmon resonance and in situ proximity ligation assay, we found that luteolin disrupted the p16-CDK6 interaction. This work demonstrates that administration of HK promotes longevity in mice, possibly by modulating cellular senescence and by disrupting the p16-CDK6 interaction.

A two-tiered high-flow nasal cannula approach does not increase intensive care utilization and hospital length of stay in bronchiolitis.

While concerns about high-flow nasal cannula oxygen (HFNC) overuse and associated increased use of hospital resources are rapidly spreading, a two-tiered approach in its use is recommended by recent bronchiolitis guidelines. However, data on its effects in practice have not been reported. We aimed to analyze the trends in use of HFNC, hospitalizations, length of stay (LOS), and intensive care unit (ICU) admissions for bronchiolitis in a tertiary care center using a two-tiered HFNC approach since its introduction in practice. We retrospectively included data of children < 12 months of age who presented to the Paediatric Emergency Department (PED) and were hospitalized for bronchiolitis at our institution in the epidemic season between October 1st and April 30th during the years 2012-2023 and compared the clinical data across the years. Of the 687 hospitalized children included, 79.9% required oxygen supplementation. Use of HFNC significantly increased since its implementation (from 25% in 2012-2013 to over 60% since 2019-2020, p < 0.0001) and was most frequently administered as rescue treatment (in 57.5% of patients). There was no increased trend in ICU admissions (between 1.5% and 10.0% of hospitalizations across seasons, p = 0.40), while LOS, after increasing between 2013 and 2016 (medians between 4.0 and 5.4 days), remained stable thereafter (medians between 3.8 and 4.3 days). CONCLUSIONS: The use of HFNC according to a two-tiered approach does not appear to be associated with an increase in ICU utilization or LOS. WHAT IS KNOWN: • Bronchiolitis is one of the most common reasons for hospitalization in infants. • Use high-flow nasal canulae oxygen (HFNC) has rapidly spread outside the intensive care unit (ICU) to treat infants with bronchiolitis, although increasing evidence has dampened the initial enthusiasm about their effectiveness. • Concerns nowadays are rising about HFNC overuse and associated increased use of hospital resources, including escalation of care to ICU. WHAT IS NEW: • A more selective use of HFNC according to a "two-tiered approach", intended as a second-line rescue treatment in non-severely ill children who fail standard oxygen therapy, is not associated with increased ICU and length of hospital stay.

Use of a Large Language Model to Identify and Classify Injuries With Free-Text Emergency Department Data.

This cross-sectional study assesses the accuracy, sensitivity, and specificity of a large language model used to process unstructured, non-English emergency department (ED) data in medical records.

Association Between Early-Life Exposure to Antibiotics and Development of Child Obesity: Population-Based Study in Italy.

BACKGROUND: Childhood obesity is a significant public health problem representing the most severe challenge in the world. Antibiotic exposure in early life has been identified as a potential factor that can disrupt the development of the gut microbiome, which may have implications for obesity. OBJECTIVE: This study aims to evaluate the risk of developing obesity among children exposed to antibiotics early in life. METHODS: An Italian retrospective pediatric population-based cohort study of children born between 2004 and 2018 was adopted using the Pedianet database. Children were required to be born at term, with normal weight, and without genetic diseases or congenital anomalies. We assessed the timing of the first antibiotic prescription from birth to 6, 12, and 24 months of life and the dose-response relationship via the number of antibiotic prescriptions recorded in the first year of life (none, 1, 2, and ≥3 prescriptions). Obesity was defined as a BMI z score >3 for children aged ≤5 years and >2 for children aged >5 years, using the World Health Organization growth references. The obese incidence rate (IR) × 100 person-years and the relative 95% CI were computed using infant sex, area of residence, preschool and school age, and area deprivation index, which are the covariates of interest. A mixed-effect Cox proportional hazards model was used to estimate the hazard ratio and 95% CI for the association between antibiotic exposure in early life and child obesity between 24 months and 14 years of age, considering the family pediatricians as a random factor. Several subgroup and sensitivity analyses were performed to assess the robustness of our results. RESULTS: Among 121,540 children identified, 54,698 were prescribed at least an antibiotic within the first year of life and 26,990 were classified as obese during follow-up with an incidence rate of 4.05 cases (95% CI 4.01-4.10) × 100 person-year. The risk of obesity remained consistent across different timings of antibiotic prescriptions at 6 months, 1 year, and 2 years (fully adjusted hazard ratio [aHR] 1.07, 95% CI 1.04-1.10; aHR 1.06, 95% CI 1.03-1.09; and aHR 1.07, 95% CI 1.04-1.10, respectively). Increasing the number of antibiotic exposures increases the risk of obesity significantly (P trend<.001). The individual-specific age analysis showed that starting antibiotic therapy very early (between 0 and 5 months) had the greatest impact (aHR 1.12, 95% CI 1.08-1.17) on childhood obesity with respect to what was observed among those who were first prescribed antibiotics after the fifth month of life. These results were consistent across subgroup and sensitivity analyses. CONCLUSIONS: The results from this large population-based study support the association between early exposure to antibiotics and an increased risk of childhood obesity. This association becomes progressively stronger with both increasing numbers of antibiotic prescriptions and younger age at the time of the first prescription.

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.

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.

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.

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.

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.