搜索结果：Italian journal of pediatrics

Treating obesity in children and adolescents is complex, given the dynamic nature of growth and development during this life stage. The role of pharmacological treatments in the management of pediatric obesity remains uncertain, particularly with respect to outcomes beyond weight reduction, including quality of life and long-term adverse events. To assess the benefits and harms of pharmacological interventions for the treatment of obesity in children and adolescents. We searched CENTRAL, MEDLINE, the World Health Organization (WHO) International Clinical Trials Registry Platform, and ClinicalTrials.gov on 3 July 2023 without language restrictions. In June 2025, we checked the status of ongoing studies and updated results accordingly. We included randomized controlled trials (RCTs) evaluating pharmacological interventions in children (0 to 9 years) and adolescents (10 to 19 years) with essential obesity. Eligible studies administered any medication, at any dose, as monotherapy or in combination, for at least three months and reported outcomes after a minimum follow-up of six months. Critical outcomes were change in body mass index (BMI), change in weight, any adverse events, discontinuation due to adverse events, and incidence or severity of obesity-related outcomes. Important outcomes were health-related quality of life, mental and physical well-being, and obesity-related disability. We used the RoB 2 tool to assess bias in the included RCTs. We calculated mean differences (MDs) and standardized mean differences (SMDs) for continuous outcomes and risk ratios (RRs) for dichotomous outcomes, with their corresponding 95% confidence intervals (CIs). We used GRADE to assess the certainty of evidence for critical outcomes and quality of life. We included 37 RCTs with a total of 4218 participants. Two were cross-over trials; 35 were parallel-group trials. We identified seven ongoing studies and six studies as awaiting classification. Of the included studies, 25 involved adolescents only. Eleven studies planned to include both children and adolescents, but only eight actually did. One study intended to include children but did not specify participants' age at inclusion. Trials randomized participants to pharmacological interventions or control alongside common baseline treatments (e.g. behavioral or lifestyle approaches, diet, and physical activity). Of the 37 included studies, 31 used placebo and six used no intervention (baseline treatment alone) as the comparator. The studies were conducted across 17 high-income, six middle-income, and three low-income countries. Length of follow-up ranged from six to 31 months, with a median of 11 months. Pharmacological interventions versus placebo Compared to placebo, pharmacological interventions (glucagon-like peptide-1 [GLP-1] receptor agonists, metformin, orlistat, sibutramine, topiramate, phentermine plus topiramate) may reduce BMI (change from baseline) by 1.80 kg/m2 (95% CI -2.36 to -1.24; I2 = 87%; 25 studies, 3091 participants; low-certainty evidence) and weight (change from baseline) by 5.47 kg (95% CI -7.45 to -3.50; I2 = 89%; 20 studies, 2380 participants; low-certainty evidence). Adverse events were frequent. Pharmacological interventions (GLP-1 agonists, sibutramine, phentermine, topiramate) likely make little to no difference in the risk of any adverse events compared to placebo (RR 1.03, 95% CI 1.00 to 1.07; I2 = 0%; 8 studies, 1877 participants; moderate-certainty evidence). Pharmacological interventions (GLP-1 agonists, metformin, orlistat, sibutramine, phentermine, topiramate) may make little to no difference in the risk of discontinuation due to adverse events, although the risk was slightly higher with the medications (RR 1.50, 95% CI 0.82 to 2.75; I2 = 17%; 13 studies, 2213 participants; low-certainty evidence). One study (46 participants), comparing sibutramine to placebo, found that there may be little to no difference in the incidence of obesity-related outcomes for adolescents with comorbidities (assessed as changes in glycemia, blood pressure, total cholesterol, and triglycerides). We were unable to pool other data on incidence or severity of obesity-related outcomes. Compared to placebo, pharmacological interventions (GLP-1 agonists, phentermine plus topiramate) likely result in little to no difference in quality of life, assessed with the Impact of Weight on Quality of Life-Kids (IWQOL) questionnaire (MD 1.02, 95% CI -1.94 to 3.98; I2 = 48%; 4 studies, 741 participants; moderate-certainty evidence). Pharmacological interventions versus no intervention Compared to no intervention, metformin may reduce BMI (change from baseline) by 1.51 kg/m2 (95% CI -2.29 to -0.73; I2 = 0%; 3 studies, 151 participants) and weight (change from baseline) by 3.20 kg (95% CI -6.12 to -0.28; 1 study, 42 participants), but the evidence for both outcomes is very uncertain. Compared to no intervention, pharmacological interventions (metformin and orlistat) may increase the risk of discontinuations due to adverse events, but the evidence is very uncertain (RR 13.70, 95% CI 0.83 to 225.43; 2 studies, 84 participants). None of the studies comparing pharmacological interventions to no intervention reported data on adverse events, obesity-related outcomes, and quality of life that could be pooled in meta-analysis. Only eight of the 37 included studies enrolled children, and data were seldom disaggregated by age, limiting the ability to draw conclusions about benefits or harms in children. This review includes clinical trials assessing the benefits and harms of pharmacological treatments - including GLP-1 agonists, metformin, orlistat, phentermine, sibutramine, and topiramate - for weight management in adolescents with obesity. Evidence suggests that pharmacological treatments may result in small reductions in BMI and weight, which could be clinically important, although effects vary by medication. Evidence on desirable and undesirable effects in children is scant. Uncertainties remain about the optimal duration of treatment, consequences of treatment discontinuation, and long-term benefits and harms, particularly considering the physiology of children and impact on growth. Studies with longer follow-up are needed to evaluate outcomes beyond BMI and weight change, including the potential effects of treatment discontinuation. The Department of Nutrition and Food Safety at the WHO commissioned and provided financial support for this work. WHO acknowledges financial support from the Norwegian Agency for Development Cooperation (NORAD), the Swedish International Development Cooperation Agency (SIDA), the Government of the Grand Duchy of Luxembourg, the Government of Germany (BMG), and the Government of Greece to the WHO Department of Nutrition and Food Safety. Our protocol is registered in PROSPERO: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433123.

Inherited epidermolysis bullosa comprises a heterogeneous group of skin fragility diseases, presenting with a range of manifestations and complications that profoundly affect quality of life (QoL). A disease-specific instrument, Quality of Life in EB (QOLEB), has been developed to assess the impact of epidermolysis bullosa signs and symptoms on QoL. The aim of this cross sectional study, conducted as part of a European project - BUR-EB, was to test the psychometric properties of the Italian version of the QOLEB and to assess QoL in Italian epidermolysis bullosa patients. Demographic, clinical, and QOLEB data of 56 Italian patients aged ≥11 years participating in the BUR-EB online survey were analysed. Principal component analysis showed excellent internal consistency of Italian QOLEB, and high convergent validity with the generic questionnaire EQ-5D. About 40% of patients reported severe to very severe disease burden, and a strong correlation was observed between disease severity and QOLEB scores. Independent variables associated with worse QoL were pain, chronic wounds, wheelchair use and patient organization membership. Our study confirms the good psychometric properties of the Italian QOLEB. In addition to depicting the major impact of epidermolysis bullosa on QoL, it identifies pain, chronic wounds and functional disability as major targets for therapeutic interventions.

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Plexiform neurofibromas (PNs) are benign tumors that can cause pain, disfigurement, and disability in patients with neurofibromatosis type 1. Selumetinib, a MEK1/2 inhibitor, is the first drug who showed efficacy in inducing PNs shrinkage, reducing the associated morbidities in pediatric patients. Overall, selumetinib showed a good safety profile. However, multiple adverse effects have been reported both in pediatric and adult patients, including respiratory ones. Serial spirometry is suggested in patients with thoracic neurofibromas to detect changes that may underly PN's modifications. The aims of this study are to investigate the trend of pulmonary function in pediatric patients with NF1 treated with selumetinib and to determine the onset of respiratory adverse events. This is a retrospective study conducted at the Pediatric Department of the Institute for Maternal and Child Health IRCCS "Burlo Garofolo" in Trieste, Italy. We identified all the patients diagnosed with NF1 at our institution who received selumetinib. We excluded patients unable to perform spirometry at treatment start, and patients above 18 years of age. We registered patients' forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1) for the first two years of follow-up and record any possible respiratory adverse effect since the beginning of the treatment. A total of 21 patients were included (7 females, 14 males) out of the 24 treated with selumetinib. Patients' median age when selumetinib was started was 12 years. Neurofibromas were located mostly in the upper body, but 13 of them were in the thoracic area. The duration of the clinical follow-up ranged from 9 months to 72 months (6 years), with a mean follow-up length of 37 months. During the follow-up period, none of the patients reported pulmonary symptoms and no significant changes of the spirometry values were detected. Among those with thoracic plexiform neurofibromas, no correlation was found between spirometry values and PN's volumetric changes at the MRI. Our experience suggests that selumetinib does not impact on pulmonary function in children and young adults. Serial spirometry should not be mandatory or could be at least distanced since it is not an appropriate method to precisely monitor plexiform neurofibromas changes over time.

Acute otitis media (AOM) is a common pediatric infection, and spontaneous tympanic membrane perforation and otorrhea represent a clinically significant subset that requires specific management. Understanding current practices among pediatricians is crucial for identifying areas of concordance with guidelines, management strategies, and potential educational needs. A national survey was conducted among Italian pediatricians, including both family pediatricians and hospital-based specialists, to assess their attitudes and practices regarding the definition, epidemiology, diagnosis, and treatment of AOM with otorrhea. A dedicated questionnaire included 20 items concerning different aspects of AOM management, including the potentiality of topical treatment for otorrhea. Data were also stratified for age, type of work, and geographic area. Five hundred pediatricians participated in the survey. The survey revealed that 57.6% of respondents preferred "acute otitis media with otorrhea" as the disease definition. AOM with otorrhea is most frequently observed in winter (45%) and autumn/spring (25% each). Approximately two-thirds of pediatricians (66%) manage 5-20 cases monthly during peak incidence. Otorrhea is reported in <10% of AOM cases by 58.6% of practitioners. A substantial majority (80.2%) initiate antibiotic treatment at the first observation in the presence of otorrhea, primarily systemic (78.2%), with amoxicillin-clavulanate (60.2%) being the preferred drug for 8-10&#x2009;days (72.4%). Recurrences within 3&#x2009;months are reported by 72.8% of respondents, with <10% of patients reporting them. There is raised interest in treatment alternatives (85.8%) and a preference for topical administration for specific patient categories (60.6%). This national survey suggests that Italian pediatricians commonly favor early antibiotic treatment for acute otitis media with otorrhea, while areas of uncertainty remain regarding watchful waiting, treatment duration, and the role of topical therapy. These findings highlight the need for clearer, practice-oriented guidance and further research.

Language development in early childhood varies considerably, making early detection of Developmental Language Disorders (DLDs) challenging despite their high prevalence and long-term effects on learning and mental health. In Italy, no culturally adapted, easy-to-use screening tools are currently available in primary care. To address this gap, a screening tool was developed to support the early identification of children aged 24-72 months at risk of DLD and other clinically relevant language difficulties. To evaluate the psychometric properties and accuracy of the Comunicazione e Linguaggio in Ambulatorio Pediatrico (CLAP), a brief age-specific screening tool designed for use in Italian paediatric outpatient settings. In this pilot validation study, children were recruited by primary care paediatricians during routine well-child visits and stratified into four age groups: 24-30, 36-42, 48-54, and 60-72 months. After administration of the CLAP screening tool, each child underwent a blinded speech-language pathologist (SLP) assessment. Psychometric evaluation included internal consistency, item-total correlations, confirmatory factor analysis, and item response theory indices (discrimination and difficulty). Diagnostic accuracy was assessed using ROC curves, area under the curve (AUC), sensitivity, specificity, and optimal cut-offs. Analyses were conducted separately for each age group. Fifty children were enrolled in each age group; overall, 24% of the sample fell into the pathological subgroup after the blinded SLP assessment. Internal consistency was acceptable in the 24-30-month (KR-20 = 0.695) and 36-42-month (KR-20 = 0.777) groups, but lower in older children. Factor analyses supported a mainly unidimensional structure in the younger groups. Item response theory showed good discrimination and informativeness for several items. ROC analyses indicated excellent diagnostic accuracy in the 24-30-month group (AUC = 0.93; sensitivity = 92%; specificity = 87%), fair accuracy in the 36-42- and 48-54-month groups (AUC = 0.75 and 0.74), and poor performance in the 60-72-month group (AUC = 0.46). The CLAP demonstrates promising psychometric properties and good-to-fair accuracy as a brief screening tool for identifying children aged 24-54 months at risk of clinically relevant language difficulties, including those who may need further assessment for DLD. Its age-specific design, quick administration, and non-invasive nature support its potential integration into routine primary care. For older children, an age-specific revision or an alternative tool might be required. A larger validation study is currently in progress. What is already known on this subject Developmental Language Disorder (DLD) is common in early childhood; however, early identification remains difficult due to variable developmental pathways and the absence of validated screening tools in primary care. Currently, no brief, culturally adapted instrument is available for routine use in Italian paediatric settings. What does this study add to existing knowledge This study demonstrates that the CLAP tool has promising psychometric properties, with good accuracy in the youngest age group and fair accuracy up to 54 months for identifying children at risk of clinically relevant language difficulties, including those who may later meet criteria for DLD. It provides the first evidence supporting an age-specific, feasible screening option that can be integrated into Italian primary care, while also identifying areas requiring revision for older pre-schoolers. What are the potential or actual clinical implications of this work? CLAP can assist paediatricians in the early detection of clinically relevant language difficulties in children during routine well-child visits. Its adoption could help standardize early language screening in Italy, leading to earlier referral for further diagnostic assessment and appropriate speech-language evaluation.

Cough is one of the most common and distressing symptoms in pediatric practice and represents a major cause of medical consultation, parental anxiety, and inappropriate medication use. Although most acute cough episodes are benign and self-limiting, they can significantly affect child's sleep, school performance, and quality of life. The COVID-19 pandemic and subsequent changes in infection patterns and immune responses have further highlighted the need to update the existing clinical guidance. This joint position paper by the Italian Society of Pediatric Allergy and Immunology (SIAIP) aims to provide a pragmatic, evidence-based update on the management of acute and post-viral cough in children and adolescents, integrating recent scientific advances and real-world clinical experiences. A multidisciplinary board of experts from SIAIP critically reviewed the literature published from 2019 to 2025 and updated the previous 2019 SIAIP document. The group achieved consensus on diagnostic and therapeutic recommendations through structured discussion and iterative revision. The document emphasizes a stepwise approach to pediatric acute cough, starting with careful history-taking, clinical evaluation, and reassurance. Non-pharmacological measures-hydration, nasal saline irrigation, and avoidance of irritants-remain the first-line management. Pharmacological therapy may be considered in selected cases where cough is particularly distressing or significantly interferes with sleep; peripherally acting, nonsedative antitussives represent a reasonable option in terms of efficacy and safety. Centrally acting antitussives and unnecessary antibiotics should be avoided. Standardized, high-quality natural medical devices-with appropriate supporting evidence-represent a valid option. Honey-based preparations can be considered as complementary options. The paper also discusses new insights into cough pathophysiology, particularly the role of airway sensory hypersensitivity and neurogenic inflammation, which are paving the way for mechanism-based treatments. This position paper provides an updated, pragmatic framework for the management of acute and post-viral cough in children and adolescents. It promotes rational drug use, integration of non-pharmacological and complementary measures, and awareness of emerging therapeutic targets. A mechanism-driven, individualized, and family-centered approach is advocated to improve clinical outcomes and quality of life for pediatric patients.

Hemolytic uremic syndrome associated with Shiga toxin-producing Escherichia coli (STEC-HUS) infection is a major individual and public health challenge, and the leading cause of acute kidney injury in children. In Western countries, HUS complicates about 15% of STEC infections, which are responsible for acute bloody diarrhea (ABD) in at least 6&#x2013;7% of cases in children (rising to over 15% during late summer). The widespread use of molecular microbiology techniques enables the diagnosis of STEC infection before HUS onset in an increasing number of patients, creating a potential window of preventive and therapeutic opportunities. Given the rapid progression of the disease, all children with ABD should be tested for Shiga toxin (Stx) encoding genes as early as possible. Stx-positive patients should then be closely monitored for HUS development by urine dipstick, to detect hemoglobinuria.This proactive diagnostic approach creates the opportunity to anticipate the application of measures that have already been proven to mitigate the severity of HUS, among which stands the early and generous fluid administration, but most importantly opens a window to explore preventive and therapeutic interventions. In detail, even though antibiotics are not historically recommended in STEC infections, recent data suggest a promising potential preventive role for bacteriostatic agents (e.g., azithromycin) during the initial stages of the infection.The aim of the present contribution is to share this approach to ABD and STEC infection as endorsed by the Italian scientific societies actively engaged in this area (AMCLI, SIGENP, SIMEUP, SIN, SIP, SIPPS, SITIP) through an intersocietal consensus. The goal is to promote the early diagnosis of STEC infection nationwide, thereby improving our understanding of the mechanisms of disease spreading, and hopefully reduce the rate of progression to HUS, its case fatality rate and possibly improve both short- and long-term outcomes.

Energy drinks are widely marketed to enhance alertness and performance and are increasingly consumed by children and adolescents, despite warnings from pediatric and public health organizations regarding potential health risks. This study aimed to investigate energy drink consumption, age of initiation, motivations, risk perception, and awareness of health guidelines among Italian adolescents, with comparisons across distinct clinical and non-clinical subgroups. A cross-sectional survey was conducted between May and December 2025 using an anonymous questionnaire administered to adolescents aged 9-17 years. Participants were recruited from four settings: inpatients with eating disorders, other hospitalized patients, competitive athletes, and healthy controls. The questionnaire assessed demographics, familiarity and frequency of energy drink consumption, age of first use, motivations, perceived health risks, knowledge of official guidelines, and attitudes toward sales regulations. Data were analysed descriptively and using chi-square tests, with statistical significance set at p&#x2009;<&#x2009;0.05. In the study period, 430 participants were recruited. Overall, 96.5% of participants were familiar with energy drinks, and 65.1% reported at least occasional consumption. Early initiation was common, with 39.2% of consumers starting before age 12. Frequent consumption was relatively low (10.2%) but more prevalent among older adolescents and healthy controls. Only 52.3% perceived energy drinks as harmful, and awareness of official health guidelines was limited (40.4%). Consumption patterns, risk perception, and knowledge differed significantly across subgroups, with athletes showing greater awareness and eating disorder patients exhibiting higher uncertainty. Although frequent energy drink use was uncommon, early exposure and substantial knowledge gaps were identified. These findings highlight the need for routine screening, targeted education, and preventive strategies to reduce energy drink consumption and protect vulnerable pediatric populations.

This study investigated whether job satisfaction and perceptions of respect for human rights among healthcare workers and patients improved in the post-COVID period compared to during the pandemic in 2021. Conducted in October 2025 across five outpatient hospital units in Sardinia, Italy, this cross-sectional survey involved 97 healthcare professionals and 129 patients recruited voluntarily based on service requirements attendance. The "Well-Being at Work and Respect for Human Rights" questionnaire (WWRR) was used to assess job satisfaction, organizational climate, respect for human rights, and perceived adequacy of resources. Chi-square tests were used to compare categorical variables, and one-way ANOVA with Bonferroni correction was used to analyze mean WWRR scores. Results indicated that, compared to 2021, healthcare workers' scores remained largely unchanged, reflecting modest satisfaction and ongoing concerns about organizational factors, staffing, and resource availability. Conversely, patients reported significantly higher satisfaction, particularly in areas of care quality, organizational efficiency, and respect for rights, with notable improvements in organizational satisfaction since 2021 (p&#x202f;<&#x202f;0.0001 for all comparisons). The greatest perception gap was observed in organizational aspects, where patient scores exceeded staff scores by nearly two points. Both groups continued to express dissatisfaction with resource adequacy. Additionally, staffing needs evolved, with increased demand for administrative support, security personnel, and multidisciplinary care providers. In 2025, compared to 2021, healthcare professionals reported a significantly greater need for administrative or HR managers (14.4% vs. 0%; p&#x202f;<&#x202f;0.0001), security personnel (5.1% vs. 0.6%; p&#x202f;=&#x202f;0.023), and an increase in all professional figures or multiple types of workers (14.4% vs. 0%; p&#x202f;<&#x202f;0.0001). Similarly, user responses showed a higher perceived need for administrative or staff-managing professionals (8.5% vs. 0%; p&#x202f;<&#x202f;0.0001) and occupational therapists, educators, or rehabilitation technicians (8.5% vs. 2.1%; p&#x202f;=&#x202f;0.017). While patient trust in healthcare services has largely rebounded in the post-pandemic period, this masks ongoing challenges in restoring healthcare workers' morale and satisfaction. Persistent systemic issues strain staff well-being and threaten the quality, efficiency, and sustainability of care. Bridging the gap between renewed patient confidence and the unresolved difficulties faced by healthcare workers must become a central priority for policymakers and administrators. By improving workplace conditions, fostering supportive organizational cultures, and investing in staff development and well-being, healthcare systems can secure a durable, post-crisis recovery.

Clinical research is essential for advancing pediatric care, yet pediatricians often face unique structural, organizational, and methodological barriers that may hinder their participation in scientific activities. Understanding these obstacles is crucial to designing effective strategies that strengthen pediatric research capacity in Italy, a country with a leading role in European pediatric output. This study aimed to investigate Italian pediatricians' perceptions of barriers, facilitators, and needs related to conducting research, applying evidence in clinical practice, and publishing scientific work. We conducted a cross-sectional online survey of Italian pediatricians using an 18-item questionnaire administered between April and May 2025. Data were analyzed descriptively, and multilevel logistic regression assessed associations between perceived barriers and respondents' characteristics. A total of 717 pediatricians involved in clinical and/or research activities were included. Among those engaged in research (n&#x2009;=&#x2009;385), the most frequently reported personal barriers were difficulties balancing clinical and research duties (79.3%) and limited access to funding (67.9%). Operational issues such as delayed Ethics Committee approvals (80.8%) and challenges in multicenter data sharing (55.9%) were also prominent. Many respondents expressed dissatisfaction with current research evaluation systems: 78.2% believed that metrics should reflect long-term patient impact, and 73.1% reported that existing criteria penalize pediatric researchers in low-resource settings. Regarding scientific publishing, major obstacles included limited time (75%), complexity of data analysis (58.7%), and publication costs (55%). Interest in support initiatives was high, particularly for monthly evidence summaries (88.5%) and training in artificial intelligence tools (74.3%). Multivariate analysis revealed significant differences by age, gender, and professional role, especially concerning perceived research training adequacy and data analysis difficulties. Italian pediatricians face substantial structural, organizational, and methodological barriers to conducting research. Despite this, they show strong motivation to engage in scientific activities and express clear needs for training, infrastructural support, and improved evaluation systems. Strengthening funding opportunities, enhancing institutional support, and streamlining ethical and administrative procedures are essential to advancing pediatric research capacity and improving future child health outcomes.

Fungal infections are common worldwide and a frequent reason for pediatric primary care visits, mainly affecting the skin, hair, and nails, with a consistently high prevalence in outpatient settings. This study aimed to assess the burden of fungal infections in pediatric primary care in Italy and characterize the patterns of antifungal therapy use. This population database analysis used data from Pedianet, a comprehensive database of 193 family pediatricians in Italy. The annual incidence rate (IR) of fungal infections was evaluated in children aged&#x2009;<&#x2009;14 years from January 2010 to December 2024. Subjects were followed up from 2010 or their enrollment date until the end of assistance or the end of the study period. All antifungal treatments occurring within an episode were included. A total of 23,463 episodes of fungal infection were identified, including 23,034 episodes of skin and mucocutaneous mycoses and 429 episodes of onychomycosis. The most frequent diagnoses were Candida-associated diaper dermatitis (52.1%) and mucocutaneous candidiasis (27.4%). Between 2010 and 2019, the incidence of fungal infections remained stable at 11-14 cases per 1,000 person-years. A marked decline across all age groups was observed in 2020, reflecting the impact of the SARS-CoV-2 pandemic. Regarding treatment, 144/429 (33.6%) of onychomycosis episodes received an antifungal prescription, mainly tioconazole, while 8347/23,034 (36.3%) of skin and mucocutaneous mycoses were treated, predominantly with clotrimazole. This population-based cohort study updates the epidemiology of non-invasive fungal infections in pediatric outpatients and underscores the need for greater awareness, improved diagnosis, prevention, and antifungal stewardship in primary care.

OBJECTIVE: Intravenous immunoglobulin (IVIG) serves as the first-line therapy for Kawasaki disease (KD); however, a significant minority of patients exhibit resistance to this treatment. Currently, there is a lack of easily accessible and reliable predictors for IVIG resistance. This study systematically evaluates the utility of baseline peripheral blood cell counts and their ratios in predicting IVIG non-response. METHODS: We assembled a retrospective cohort from the Children&#x2019;s Hospital of Chongqing Medical University, including all KD patients admitted between January 1, 2023, and June 30, 2025. Patients were classified as either IVIG-responsive or IVIG-resistant based on the resolution of fever following the initial IVIG treatment. We compared baseline demographics, laboratory data, and coronary artery lesion (CAL) status. Univariable analysis was conducted to identify factors associated with IVIG resistance, and receiver-operating characteristic (ROC) curves were utilized to quantify predictive performance. RESULTS: Among the 210 children diagnosed with KD, 15 (7.1%) were classified as IVIG-resistant, while 195 (92.9%) were responsive to treatment. No significant differences were observed in sex, age at onset, or the frequency of CAL between the two groups; however, the hospital length of stay was significantly longer in the resistant cases (P&#x2009;<&#x2009;0.001). Prior to IVIG treatment, the resistant group exhibited elevated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII) (P&#x2009;=&#x2009;0.003, 0.001, 0.013, 0.029, respectively), alongside a lower absolute lymphocyte count (P&#x2009;<&#x2009;0.001). ROC analysis revealed that NLR (AUC 0.733; cut-off 1.07; sensitivity 100%, specificity 84.6%) and PLR (AUC 0.766; cut-off 64.43; sensitivity 100%, specificity 84.1%) were the most robust pre-treatment predictors of IVIG resistance. Following IVIG administration, responsive patients demonstrated significant alterations in multiple cellular parameters, whereas resistant patients exhibited only minimal changes. The extent of change was markedly different between the groups, particularly for PLR: PLR decreased in resistant patients but increased in responders. The difference in PLR before and after infusion (&#x394;PLR) provided excellent discrimination (AUC 0.840; cut-off 81.77; sensitivity 93.3%, specificity 90.3%). CONCLUSIONS: Elevated baseline NLR, PLR, MLR, and SII are identified as risk factors for IVIG resistance in KD. NLR values exceeding 1.07 and PLR values greater than 64.43 demonstrate high predictive value. A decline in post-treatment PLR of &#x2265;&#x2009;81.77 serves as an additional strong indicator of non-response to IVIG.

Sepsis remains the leading cause of in-hospital deaths among children, and there is currently a lack of precise early prediction models. This study aimed to develop an interpretable machine learning (IML) model to predict in-hospital mortality in pediatric patients diagnosed with sepsis according to the 2024 Phoenix Sepsis Diagnostic Criteria. This single-center retrospective cohort study analyzed 464,459 children who were hospitalized in the Children's Hospital Affiliated to Nanjing Medical University from January 2018 to December 2023 were screened. Based on the Phoenix Sepsis Score, 2,477 cases of childhood sepsis were finally diagnosed. The features were filtered using three methods the minimum absolute contraction and selection operator (LASSO) regression, the Boruta algorithm, and random forest importance ranking, ultimately identifying 12 features. Eight machine learning algorithms were trained on 70% of the data and evaluated on a 30% test set. The optimal model was screened based on the accuracy of the test set and the area under the receiver operating characteristic curve (AUC). The interpretability of the model is enhanced by leveraging SHapley Additive exPlanations (SHAP) summary graphs, individual SHAP force maps, and partial dependency plots (PDPs). A total of 2,477 patients with sepsis met the participation criteria, with a median age of 26 months (IQR, 5-78 months). Among the 2,477 participants, 1,448 (58.5%) were boys. The CatBoost model demonstrated the best performance among the 8 constructed models, achieving an AUC of 0.889 and an accuracy of 92.9% in the test set. Notably, at the default decision threshold, the model demonstrated high specificity but relatively low sensitivity. However, by optimizing the decision threshold using the Youden Index, the model's sensitivity was substantially improved to 83.05%, effectively mitigating the potential risk of missed diagnoses for high-risk patients in clinical practice. Feature importance analysis indicated that invasive mechanical ventilation, Glasgow Coma Scale score, platelet count, uric acid, and SpO2/FiO2 ratio were the top five features that had the greatest impact on the CatBoost model. SHAP analysis provided both global feature importance and individualised risk explanations, and the model has been deployed as a freely accessible web calculator. The IML model developed in this study provides a highly interpretable and accurate tool for the early prediction of in-hospital mortality in pediatric sepsis patients. The SHAP approach improves model interpretability and helps clinicians understand the factors driving those predictions. However, as a single-center retrospective study, the generalizability of our findings to other clinical settings may be limited. Future multi-center prospective studies are necessary to further validate the model and address its current limitations in sensitivity to minimize the risk of missing high-risk cases.

BACKGROUND: SCN1A Gene pathological variants can lead to a spectrum of epilepsy phenotypes ranging from mild genetic epilepsy with febrile seizures plus (GEFS+) to severe Dravet syndrome (DS). As most pathological variants are de novo variants, early prediction of phenotypes and prognosis is challenging, and the genotype-phenotype correlation remains unclear. METHOD: We retrospectively analyzed the clinical and genetic data of 50 children with SCN1A variant-related epilepsy to explore the relationship between variant characteristics (location, in silico prediction scores), seizure characteristics, and phenotypes. RESULTS: This study included 50 children with SCN1A variant-related epilepsy, among whom 86.0% (43/50) had onset before the age of 1, 86.0% (43/50) exhibited fever sensitivity, and 68.0% (34/50) were accompanied by developmental delay; 36.0% (18/50) experienced status epilepticus(SE), 56.0% (28/50) had cluster seizures, and 48.0% (24/50) showed abnormal electroencephalogram(EEG) within one year of onset. Genetic analysis revealed that missense mutations accounted for 62.0% (31/50), with 78.0% (39/50) being de novo variants, and 24 previously unreported pathogenic variants were identified. The DS group (16 cases) had a significantly higher incidence of SE compared to the non-DS group (P&#x2009;=&#x2009;0.041), while the non-DS group had a higher proportion of missense mutations (P&#x2009;=&#x2009;0.014). Variant region analysis indicated that N-terminal variants were strongly associated with SE, and variants in the S2-S3/S3-S4 regions were prone to causing EEG abnormalities. In terms of treatment, the ketogenic diet was effective in 80.0% (4/5) of the children, while sodium channel blockers exacerbated seizures in 66.6% (4/6) of the children. CONCLUSION: The genotype-phenotype correlation in SCN1A-related epilepsy is crucial for early diagnosis and management: missense mutations are more prevalent in non-DS phenotypes, while DS phenotypes carry a higher risk of SE. Previously unreported variant sites expand the genetic spectrum. Ketogenic diet (KD) may be an effective treatment option, and the use of Sodium channel blocker(SCB) requires caution.

Respiratory syncytial virus (RSV) remains a leading cause of bronchiolitis and hospitalization in infants across Italy, particularly during predictable seasonal outbreaks. With the 2023-2025 RSV seasons marking the first large-scale rollout of the monoclonal antibody nirsevimab, this study aimed to evaluate the implementation strategies, regional variability, and early clinical impact of RSV prophylaxis at the national level. We conducted a nationwide, multicenter, observational study across 19 Italian regions. Data were collected through the Italian Society of Pediatrics and the Italian Society of Neonatology, focusing on regional differences in rollout timing, organizational models, logistical challenges, and RSV-related hospitalizations and pediatric intensive care unit (PICU) admissions. The results highlighted significant regional heterogeneity. Northern and central regions such as Veneto, Lombardy, and Tuscany initiated prophylaxis earlier and experienced fewer logistical barriers, resulting in marked reductions in RSV hospitalizations - up to 83.7% in Friuli-Venezia Giulia. Conversely, southern and smaller central regions, including Molise, Marche, and Umbria, faced delayed starts, supply shortages, and bureaucratic challenges, leading to more modest decreases. PICU admissions mirrored these trends. Overall, the national introduction of nirsevimab correlated with a significant reduction in RSV-related morbidity, especially in regions with early, well-organized rollouts. Comparative international studies from France, Spain, and Luxembourg reinforce the Italian findings: timely and universal prophylaxis leads to substantial public health benefits. The study concludes that early campaign activation, consistent drug availability, and efficient organization are critical for maximizing the protective effect of RSV immunization.

Neonatal jaundice is a common condition, occurring in approximately 80% of term infants during the first week of life. Timely diagnosis and management are essential to prevent bilirubin-induced neurological damage. In 2022, the American Academy of Pediatrics (AAP) updated its guideline for managing hyperbilirubinemia in infants&#x2009;&#x2265;&#x2009;35 weeks' gestation, raising treatment thresholds and recommending individualized follow-up based on gestational age, neurotoxicity risk factors, and the bilirubin-treatment threshold difference. Evidence from low- and middle-income countries on the clinical impact of these guideline is limited. We conducted a prospective observational study at Panyananthaphikkhu Chonprathan Medical Center, Thailand, from February 2024 to January 2025, including 1,104 neonates&#x2009;&#x2265;&#x2009;35 weeks' gestation. All infants underwent total serum bilirubin (TSB) screening within 72&#xa0;h of birth and were managed according to the 2022 AAP guideline. Phototherapy rates, follow-up recommendations, readmissions, exchange transfusions, and cases of acute bilirubin encephalopathy were recorded. In addition, the infants' TSB values were retrospectively applied to the 2004 AAP guideline to assess eligibility for phototherapy. Among infants who did not receive phototherapy, TSB values were retrospectively applied to the Bahr 2021 nomogram to determine follow-up recommendations for comparison with management based on the 2022 AAP guideline. Phototherapy was required in 221 infants (20.0%), representing a 38% relative reduction compared with the rate observed when the 2004 AAP guideline was retrospectively applied (32%; p&#x2009;<&#x2009;0.001). Follow-up rates decreased from 56.9% under the Bahr 2021 nomogram to 52.7% under the 2022 guideline (absolute reduction, 4.3%; relative reduction, 7.5%; 95% CI, 5.91-9.03; p&#x2009;=&#x2009;0.044). Readmission occurred in 127 infants (11.5%), most commonly due to suboptimal intake. No cases of acute bilirubin encephalopathy or exchange transfusion were reported. Implementation of the 2022 AAP guideline reduces phototherapy use and unnecessary follow-up visits without increasing adverse outcomes. With clearly structured follow-up schedules and close monitoring of infants at risk of developing severe jaundice, high-risk newborns can be managed effectively and safely. These findings support the applicability of the guideline in routine clinical practice, including in middle-income countries.

BACKGROUND: Limb Girdle Muscular Dystrophy (LGMD) is a heterogeneous group of muscle diseases that are common in childhood. This study aimed to determine the clinical, histopathological, genetic features characteristics of among pediatric patients with LGMD in the &#xc7;ukurova region and to identify disease subgroups. METHODS: This study aimed to identify disease subgroups in the &#xc7;ukurova region through a retrospective review of patients with LGMD, given differences in clinical indicators that can be used for early diagnosis and disease course as well as regional variations. Frequency and descriptive analyses were performed using SPSS 21 for Windows (IBM Corp., Armonk, NY, USA). RESULTS: The most common type identified at our center was LGMD2A-R1 (51.6%). The other types were LGMD2F-R6, LGMD2D-R3 and LGMD2C-R5, in order of frequency. Among these subtypes, the earliest age of onset and diagnosis as well as the highest creatine kinase values, were observed in the LGMD2C-R5 group. Respiratory failure was notably frequent in patients with LGMD2F-R6. Early ambulation loss was detected in patients with LGMD2F-R6 and LGMD2D-R3. Muscle biopsy was performed on 9 of the 16 patients with calpainopathy and 12 of the 15 patients with sarcoglycanopathy. The diagnosis of LGMD was confirmed by genetic testing in 25 of 31 patients. Previously unidentified 3 new mutations were detected in 4 patients. CONCLUSIONS: Early diagnosis and determination of LGMD subgroups are important for the investigation of targeted treatment options and the provision of genetic counseling in the future.

Children with intellectual disability are more likely to experience chronic and neuropathic pain, which remains frequently under-recognized due to limitations in self-reporting and objective assessment tools. Epigenetic mechanisms, particularly DNA methylation, are believed to influence pain perception. This study investigates the differences in methylation patterns between children with intellectual disability and their age- and sex-matched neurotypical controls. A cross-sectional study was carried out from March 2022 to July 2023 at the IRCCS Burlo Garofolo in Trieste, Italy. The methylation profiles of children with severe to profound intellectual disabilities and a history of recurrent pain episodes were compared to those of healthy controls. Whole blood DNA was analysed through bisulfite conversion and microarray technology, focusing on CpG islands, gene regions, and enhancers. Seventy-two participants were enrolled, including 36 children with intellectual disability and 36 without. The analysis identified four Differentially Methylated Regions (DMRs). DMR1, located within the *RNF39* gene, was found to be hypomethylated in children with intellectual disabilities. Similarly, DMR2, upstream of *VTRNA2-1* and *MIR886*, and DMR4, at the 5'UTR of *AURKC*, were also hypomethylated. In contrast, DMR3, positioned upstream of *IRF6*, was hypermethylated in the intellectual disability group. These findings indicate that children with intellectual disability exhibit distinct methylation patterns of genes related to pain pathways compared to their healthy peers. Additional research is needed to investigate the clinical relevance of these epigenetic alterations and their potential as biomarkers for pain in this population.