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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 tim

Background: The Northwestern Assessment of Verbs and Sentences (NAVS) assesses verb and sentence production and comprehension in aphasia. Results from the original English version and from its adaptation to German have shown that the NAVS is able to capture effects of verb-argument structure (VAS) complexity (i.e., lower accuracy for two- and three-argument vs. one-argument verbs) and syntactic complexity (i.e., lower accuracy for non-canonical vs. canonical sentences) in both agrammatic participants and individuals with fluent forms of aphasia. The NAVS has been recently adapted to Italian (NAVS-I) and tested on a group of healthy participants, with results showing longer reaction times to complex vs. simple verbs and sentences. Aims: The present study aimed to test the ability of NAVS-I to i) capture verb/sentence production and comprehension deficits in Italian-speaking individuals with agrammatism or with fluent aphasia, and ii) differentiate individuals with aphasia from healthy age-matched participants, with the overall goal to validate its use in clinical practice. Methods & Procedures: Forty-four healthy participants and 28 individuals with aphasia (10 with agrammatic speech production) were administered the NAVS-I, which includes tasks assessing production and comprehension of verbs requiring one, two or three arguments, as well as production and comprehension of canonical and non-canonical sentences. Outcomes & Results: On the Verb Naming Task (VNT), better production of one- (vs. two- and three-) argument verbs was found in the agrammatic group, whereas, verb production in the fluent group was solely predicted by word length and imageability. No effects of argument optionality (i.e., greater difficulty for optionally transitive verbs than for 1-argument verbs) were found. Sentence-level tasks found no differences between the agrammatic and the fluent group in production or comprehension of both canonical and non-canonical sentences; rather, senten

Purpose: To evaluate the reliability of the Deauville score (DS) in therapy response assessment and to define the prognostic value of the metabolic response of end of induction (EOI) [18F]FDG PET (PET) in follicular lymphoma patients. Methods: Adult patients with untreated grade 1-3a FL/ stage II-IV enrolled in the multicentre, prospective, phase III FOLL12 trial (NCT02063685) were randomized to receive standard immunochemotherapy followed by rituximab maintenance (standard arm) versus standard immunochemotherapy followed by response-adapted post-induction management (experimental arm). Baseline and EOI PET were mandatory for the study. All PET scans were centralized on the WIDEN® platform and classified according to DS in a blind independent central review. DS1-3 was considered negative (CMR), whereas DS4-5 was considered positive (not CMR). The primary endpoint was PFS. The main secondary endpoint was overall survival (OS). Results: Overall, 807 follicular lymphoma patients-52% women, 89% stage III-IV disease, 40% with a high-risk FLIPI-2 score (3-5)-were enrolled in the study; 729 (90.4%) baseline and EOI PET were available for the analysis. EOI PET was positive (DS4-5) in 88/729 (12.1%) cases. Overall inter-reviewer agreement on PET pos/neg result was 0.92, while agreement on positive and negative cases was 0.77 and 0.94, respectively. The median follow-up was 69 months; 247 events were registered in the 5-yr follow-up, with a 5-yr PFS of 67% (95%CI: 63%-70%). The 5-yr PFS rate for PET neg (DS1-3) and PET pos (DS4-5) patients was 71% (95%CI: 67%-75%) and 36% (95%CI: 25%-46%), respectively, with HR 3.49 (95%CI: 2.57-4.72). Five-year PFS was worse as DS increased, with 74% (70%-78%), 58% (48%-67%; HR 1.71; p = 0.001)] and 36% (25%-46%; HR 3.88; p < 0.001) in DS1-2, DS3 and DS4-5, respectively. EOI PET maintained its prognostic value in both the standard and experimental arms. In the whole population, 5-yr OS was 94% (95%CI: 92%-96%), with 96% (95%CI: 94-97

Respiratory tract infections (RTIs) are the most common infectious syndromes, primarily caused by viruses. The primary objective was to compare the illness courses between historical RTIs and recent SARS-CoV-2 infections. The study cohort consisted of RTI cases evaluated at the Pediatric Emergency Departments of Padua and Bologna, discharged or admitted with microbiologically confirmed viral RTI between 1 November 2018 and 30 April 2019 (historical period) and 1 March 2020 and 30 April 2021 (recent period). We evaluated the risk of oxygen or respiratory support, hospitalization, antibiotic therapy, and complications among different viral infections. The odds ratio (OR) and the 95% confidence intervals (CIs) were estimated through mixed-effect logistic regression models, including a random intercept on the individual and hospital. We identified 767 RTIs: 359 in the historical period compared with 408 SARS-CoV-2 infections. Infections of SARS-CoV-2 had a lower risk of being admitted (OR 0.04, 95% CI 0.03-0.07), receiving respiratory support (OR 0.19, 95% CI 0.06-0.58), needing antibiotic therapy (OR 0.35, 95% CI 0.22-0.56) and developing complications (OR 0.27, 95% CI 0.14-0.51) compared to all other viral RTIs. COVID-19 in children is clinically similar to other viral RTIs but is associated with a less severe infection course. Thus, most prevention strategies implemented for SARS-CoV-2 should still be considered during RSV and Influenza epidemics

Introduction: The COVID-19 pandemic induced an extraordinary impact on public mental health to a degree not completely understood, especially in vulnerable populations such as breast cancer (BC) survivors. In this study, we described the short- (after 3-month) and long- (after 12-month) term effects of a multidisciplinary home-based lifestyle intervention in Italian women BC survivors during the first year of COVID-19 pandemic. Materials and methods: In total, 30 Italian BC survivors with risk factors for recurrence took part in the ongoing MoviS trial (protocol: NCT04818359). Between January 2020 and January 2021, a 3-month lifestyle intervention based on psychological counseling, nutrition, and exercise was carried out. Participants were asked to fill out psychological questionnaires for the assessment of quality of life (QoL) indicators (European Organization for Research and Treatment of Cancer QoL, EORTC-QLQ-C30) and psychological health measures such as fatigue (Brief Fatigue Inventory, BFI), distress (Distress Thermometer, DT and Psychological Distress Inventory, PDI), cancer-related fatigue (Verbal Rating Scale, VRS), and mood states (Profile of Mood States Questionnaire, POMS). IBM SPSS Statistical Software version 27.0 and R Project for Statistical Computing version 4.2.1 were used to process data. All participants were assessed at four time points: T0 (baseline), T1 (3-month), and follow-up at T2 and T3 (6- and 12-month, respectively) to measure primary (quality of life indicators) and secondary (psychological health) outcomes. Friedman non parametric test and Wilcoxon signed rank test (with Bonferroni correction) were conducted to investigate the statistically significant differences in psychometric scores and between assessment times. Results: Compared to baseline (T0), at T1 most of the QoL indicators (i.e., symptoms of fatigue and general health) were improved (p < 0.017) with the exception of a worsening in participants' social functioning ability

Introduction With the aim of implementing common policies of health promotion to counter the use of tobacco cigarettes and new products and e-cig at university, the UNIVERSITY SMOKE-FREE network was set up in Italy. Objective The main objectives of the network are: to update and uniform the university regulations; to investigate exposure of students and staff to active and passive smoking by means of a multicentre survey; to implement initiatives for helping students to stop smoking; to produce information and teaching materials. Material and Methods With the involvement of the university governments, a network was set up comprising 14 universities: Milan La Statale (UNIMI), Milan-Bicocca, Milan-Humanitas, Brescia, Insubria, Pavia, Bergamo, Rome Sapienza, Parma, Padua, Florence, Urbino, the Polytechnic University of Marche, and Palermo. In order to carry out the survey, a questionnaire was developed and validated1, investigating active cigarette smoking, use of new products, exposure to passive smoking, knowledge of the health effects of smoking, and knowledge of, and agreement on regulations. Results All network universities have started to review and update their smoke-free regulations. The survey protocol, developed at UNIMI, was shared among the universities for approval by their respective Ethics Committees. The survey was completed in 2021 by the University of Milan La Statale, and in May-July 2023 by the Universities of Brescia and Urbino, while it will be conducted in the other universities in 2024. To date, more than 10000 students participated in the survey (11-25% of students). First results show differences among universities and scientific and humanistic faculties, in terms of active and passive smoking, and awareness of risks of smoking2. Conclusions The establishment of the UNIVERSITY SMOKE-FREE network is an important step to counter smoking at university. Conducting a multicentre survey may be useful to develop information material and implement com

Aim: Children have largely been unaffected by severe COVID-19 compared to adults, but data suggest that they may have experienced new conditions after developing the disease. We compared outcomes in children who had experienced COVID-19 and healthy controls. Methods: A retrospective nested cohort study assessed the incidence rate of new-onset conditions after COVID-19 in children aged 0–14 years. Data were retrieved from an Italian paediatric primary care database linked to Veneto Region registries. Exposed children with a positive nasopharyngeal swab were matched 1:1 with unexposed children who had tested negative. Conditional Cox regression was fitted to estimate the adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the exposure and outcome associations after adjusting for covariates. Results: We compared 1656 exposed and 1656 unexposed children from 1 February 2020 to 30 November 2021. The overall excess risk for new-onset conditions after COVID-19 was 78% higher in the exposed than unexposed children. We found significantly higher risks for some new conditions in exposed children, including mental health issues (aHR 1.8, 95% CI 1.1–3.0) and neurological problems (aHR 2.4, 95% CI 1.4–4.1). Conclusion: Exposed children had a 78% higher risk of developing new conditions of interest after COVID-19 than unexposed children.

Background: Bronchiolitis is the most common lower respiratory tract infection (LRTI) in children and is mainly caused by the Respiratory Syncytial Virus (RSV). Bronchiolitis presents seasonally and lasts about five months, usually between October to March, with peaks of hospitalizations between December and February, in the Northern Hemisphere. The burden of bronchiolitis and RSV in primary care is not well understood. Materials and methods: This retrospective analysis used data from Pedianet, a comprehensive paediatric primary care database of 161 family paediatricians in Italy. We evaluated the incidence rates (IR) of all-cause bronchiolitis (ICD9-CM codes 466.1, 466.11 or 466.19), all-cause LRTIs, RSV-bronchiolitis and RSV-LRTIs in children from 0 to 24 months of age, between January 2012 to December 2019. The role of prematurity (<37 weeks of gestational age) as a bronchiolitis risk factor was evaluated and expressed as odds ratio. Results: Of the 108,960 children included in the study cohort, 7,956 episodes of bronchiolitis and 37,827 episodes of LRTIs were recorded for an IR of 47 and 221 × 1,000 person-years, respectively. IRs did not vary significantly throughout the eight years of RSV seasons considered, showing a seasonality usually lasting five months, between October and March, while the peak of incidence was between December and February. Bronchiolitis and LRTI IRs were higher during the RSV season, between October and March, regardless of the month of birth, with bronchiolitis IR being higher in children aged ≤12 months. Only 2.3% of bronchiolitis and LRTI were coded as RSV-related. Prematurity and comorbidity increased the risk of bronchiolitis; however, 92% of cases happened in children born at term, and 97% happened in children with no comorbidities or otherwise healthy. Conclusions: Our results confirm that all children aged ≤24 months are at risk of bronchiolitis and LRTI during the RSV season, regardless of the month of birth, gestational age

Using electronic data from a large population-based network of Family Paediatricians (Pedianet), we aimed to describe the use of topical antimicrobials, including ozenoxacin 1% cream, in impetigo in children in Italy. We included 2929 children aged 6 months-14 years from 2016 to 2019 with at least one episode of impetigo treated with topical antimicrobials. Overall, 3051 cases of impetigo were included in the analysis. Treatment started in most cases on the same day as the impetigo diagnosis and lasted around eight days. In about 8% of the cases, a systemic antibiotic was prescribed after the topical antimicrobial, usually after 4-14 days. In this study, ozenoxacin was used in 8% of the cases. Treatment duration was significantly shorter for patients prescribed ozenoxacin compared to the whole study population (median of six vs. seven days, respectively). In contrast, the rate of treatment failure was similar. Very few adverse reactions were identified.

Background: In Europe, influenza vaccination coverage in the pediatric population is low. This study describes the influenza incidence and associated healthcare utilization in the pediatric population in Italy. Methods: Deidentified data from electronic medical records for children 0-14 years old seen by >150 family pediatricians in the Pedianet network in Italy were evaluated for 10 influenza seasons spanning 2010-2020. Incidence of influenza (cases per 1000 person-months), related sequelae and associated healthcare resource use were determined using diagnostic, prescription and medical examination data. Results: Over 10 seasons, an average of 8892 influenza cases (range, 4700-12,419; total 88,921) were diagnosed in a cohort of 1,432,384 children 0-14 years of age. Influenza vaccination coverage was 3.6% among children with an influenza diagnosis and 6.8% among children without. Influenza-related healthcare resource utilization included 1.58 family pediatrician visits per influenza episode and 220 ED and 111 hospital admissions, with the highest resource usage among children 1-4 years and lowest among children <6 months old. The most common influenza complications were acute otitis media (2.9% of influenza cases) and pneumonia (0.5%). Antibiotics were prescribed in 38.7% of influenza cases; no antiviral agents were prescribed. One intensive care unit admission and 2 cases requiring ventilatory support were documented. No influenza-related deaths were reported. Conclusion: Pediatric influenza vaccination was low despite the burden and healthcare use related to seasonal influenza in the pediatric population during a 10-year period in Italy.

Despite widespread childhood immunization programs, pneumococcal disease (PD) continues to be associated with significant clinical and economic burden worldwide. This retrospective study assessed the PD-related economic burden in children from the Veneto region of Italy following the introduction of a 13-valent pneumococcal conjugate vaccine (PCV13) to the Italian immunization schedule in 2010. Between 2010 and 2017, the annual incidences of pneumonia, acute otitis media (AOM), and invasive pneumococcal disease (IPD), as well as syndromic-disease-related episodes, declined. In our analysis of data from regional expenditure and healthcare resource utilization (HCRU) databases related to children < 15 years of age, we found that regional expenditures decreased between 2010 and 2017 for pneumonia (EUR 8.88 to EUR 3.59 million), AOM (EUR 3.78 to EUR 2.76 million), and IPD (EUR 1.40 to EUR 1.00 million). Despite reductions in PD-related expenditure following the introduction of PCV13, there continues to be an economic burden associated with PD in Veneto, Italy.

Fever is one of the most common causes of medical evaluation of children, and early discrimination between viral and bacterial infection is essential to reduce inappropriate prescriptions. This study aims to systematically review the effects of point-of-care tests (POCTs) and rapid tests for respiratory tract infections on changing antibiotic prescription rate, length of stay, duration of therapy, and healthcare costs. Embase, MEDLINE, and Cochrane Library databases were systematically searched. All randomized control trials and non-randomized observational studies meeting inclusion criteria were evaluated using the NIH assessment tool. A meta-analysis was performed to assess the effects of rapid influenza diagnostic tests and film-array respiratory panel implementation on selected outcomes. From a total of 6440 studies, 57 were eligible for the review. The analysis was stratified by setting and POCT/rapid test type. The most frequent POCTs or rapid tests implemented were the Rapid Influenza Diagnostic Test and film-array and for those types of test a separate meta-analysis assessed a significant reduction in antibiotic prescription and an improvement in oseltamivir prescription. Implementing POCTs and rapid tests to discriminate between viral and bacterial infections for respiratory pathogens is valuable for improving appropriate antimicrobial prescriptions. However, more studies are needed to assess these findings in pediatric settings.

BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines.METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events.FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively.INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates.FUNDING: The projec

The oncogenic role of common fragile sites (CFS), focal and pervasive gaps in the cancer genome arising from replicative stress, remains controversial. Exploiting the TCGA dataset, we found that in most CFS the genes residing within the associated focal deletions are down-regulated, including proteins involved in tumour immune recognition. In a subset of CFS, however, the residing genes are surprisingly overexpressed. Within the most frequent CFS in this group, FRA4F, which is deleted in up to 18% of cancer cases and harbours the CCSER1 gene, we identified a region which includes an intronic, antisense pseudogene, TMSB4XP8. TMSB4XP8 focal ablation or transcriptional silencing elicits the overexpression of CCSER1, through a cis-acting mechanism. CCSER1 overexpression increases proliferation and triggers centrosome amplifications, multinuclearity, and aberrant mitoses. Accordingly, FRA4F is associated in patient samples to mitotic genes deregulation and genomic instability. As a result, cells overexpressing CCSER1 become sensitive to the treatment with aurora kinase inhibitors. Our findings point to a novel tumourigenic mechanism where focal deletions increase the expression of a new class of “dormant” oncogenes.

INTRODUCTION AND OBJECTIVE: Community-acquired pneumonia (CAP) is one of the most common reasons of prescribing antibiotics for children, often with overuse of broad-spectrum antibiotics. The aim of this study is to describe the antibiotic prescriptions for Italian children with CAP, at the primary care level. STUDY DESIGN: Retrospective cohort study conducted among children 3 months-14 years of age with CAP, enrolled in Pedianet (http://www.pedianet.it) from January 1, 2009 to December 31, 2018. Antibiotic treatment was defined as narrow-spectrum (NS-ABT) if amoxicillin and broad-spectrum (BS-ABT) if amoxicillin/clavulanic acid, cephalosporins or any combination. Crude and adjusted logistic regressions for the odds of receiving NS-ABT were conducted (all episodes of CAP and per patient). A P value <0.05 was considered statistically significant. RESULTS: Among 9691 CAP, 7260 episodes from 6409 children followed by 147 pediatricians were analyzed. The 16.7% of CAP [1216/7260, 95% confidence interval (CI): 15.9%-17.6%] received an NS-ABT while 53.3% (3863/7260, 95% CI: 52%-54.4%) received BS-ABTs and 30% (2181/7260, 95% CI: 28.9%-31.1%) macrolides. Within 10 years, a slight but increasing trend of NS-ABT prescription was observed (P < 0.001). Factors independently associated with reduced odds of receiving an NS-ABT compared with BS-ABT including macrolides were being older than 5 years [odds ratio (OR) 0.45, 95% CI: 0.39-0.52], living in Central/Southern Italy (OR 0.13, 95% CI: 0.10-0.16) and being exposed to ABT 3 months before (OR 0.61, 95% CI: 0.53-0.70). These findings were confirmed comparing NS-ABT versus BS-ABT excluding macrolides (n = 5079) and when the analysis was limited to index CAP. CONCLUSION: Our findings report a very limited prescription of narrow-spectrum antibiotics for Italian children with CAP.