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.
The burden of perioperative complications following pediatric surgery in sub-Saharan Africa is high. Assessment of the patterns and determinants of such complications and their relationship to perioperative mortality are important in identifying indicators of poor outcomes. In this study, we aim to define predictors of perioperative mortality at a tertiary hospital in Nigeria. This was a retrospective review of medical records between January 2014 and December 2023. We included patients aged 15 years and below, who had general pediatric, oncological or urological surgery under general anesthesia. Information extracted included biodata, diagnosis, American Society of Anesthesiology (ASA) classification of physical status, time of death after surgery, cause of death, and duration of surgery. Data were processed using univariate and multivariate statistical analysis. A total of 1621 patients were analyzed. The 30-day perioperative mortality rate was 2.96% (296 per 10 000 patients). Jejuno-ileal atresia, gastrochisis, and bladder exstrophy were associated with the highest mortality rates, well above 50%. Logistic regression identified neonatal age, ASA class greater than II, prolonged surgery, and repeated surgical procedures as significant predictors of mortality. Sepsis and intestinal or anastomotic failure were identified as the most common direct causes of death. Neonatal age, ASA class greater than II and prolonged and repeated surgery are significant predictors of mortality in children's surgery in our practice. Efforts should be made to combat sepsis and provide physiologic support and intensive care provision to improve outcomes.
Better evaluation of the contribution of the main diseases, injuries, and risk factors for mortality and life expectancy is crucial for more efficient policy making at the national and subnational levels in Iran. The aim of this study is to assess the effect of emerging causes of mortality on health, specifically COVID-19, which can help policy makers implement preventive measures in similar situations. In this systematic analysis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we present estimates of cause-specific mortality at the national and subnational levels in Iran from 1990 to 2023. New to this iteration of GBD, we present a decomposition analysis of the contribution of specific causes of death to net gain or loss in life expectancy across 31 provinces of Iran. We used an array of data sources including censuses, vital registration, and surveys for national and subnational estimates. The two leading causes of death in Iran were ischaemic heart disease and stroke in both 1990 and 2019. However, in 2020 and 2021, the COVID-19 pandemic displaced the leading causes of death, ranking first with age-standardised mortality rates of 286·2 deaths (95% uncertainty interval 267·9-310·5) per 100 000 in 2020 and 250·0 deaths (233·2-272·5) per 100 000 in 2021. COVID-19 ranked second and tenth in 2022 and 2023, respectively. Life expectancy at birth for both sexes combined declined from 78·0 years (77·7-78·1) in 2019 to 74·3 years (74·0-74·4) in 2020. It steadily recovered to 78·8 years (78·5-79·2) in 2023. COVID-19 was the main cause of loss in life expectancy, by 4·19 years, between 2019 and 2020. There was a net gain of 12·4 years in life expectancy in Iran from 1990 to 2023. The net gain at the national level can be mostly attributed to reduced mortality from ischaemic heart disease (2·61 years), stroke (1·63 years), neonatal disorders (1·26 years), transport injuries (0·88 years), and neoplasms (0·64 years). The decline in mortality rates of major causes continued to 2023 despite the pandemic. An exception was Alzheimer's disease, which showed a 4·0% increase in rate between 2019 and 2023 and led to a net loss of 0·04 years in life expectancy since 1990. Diabetes led to a net loss of 0·09 years since 1990. There were variations between provinces in terms of age-standardised rates and the net change in life expectancy before and after the COVID-19 pandemic. The COVID-19 pandemic disrupted the rising trend of life expectancy in Iran, varying across provinces. Findings show that the health-care infrastructure and policies in Iran were not efficient in controlling the pandemic in 2020 and 2021, mainly due to inadequate vaccination coverage and timeliness, specifically for vulnerable subgroups. Sanctions may have aggravated the effect of COVID-19 on loss in life expectancy of Iranians. Despite the pandemic, the declining trend in age-standardised rates for top causes of mortality has continued to 2023, leading to a full recovery of life expectancy and underscoring the ultimate resilience of Iran's health system. Gates Foundation.
Ritlecitinib, an oral selective inhibitor of Janus kinase 3 and the TEC family of kinases, has recently been approved for the treatment of severe alopecia areata, but real-world data are still limited. The aim was to evaluate the effectiveness and tolerability of ritlecitinib 50 mg/day after 24 weeks in patients with severe alopecia areata in clinical practice. We performed an Italian observational, retrospective, multicentre study with 24 weeks of follow-up. Patients ≥ 12 years of age with severe alopecia areata (Severity of Alopecia Tool [SALT] ≥ 50) and a disease duration ≥ 6 months who were candidates for systemic therapy were enrolled. Ritlecitinib 50 mg/day was administered according to national guidelines. The primary endpoint was to evaluate the achievement of SALT ≤ 20 at week 24. Secondary endpoints included achievement of SALT ≤ 10; mean change in SALT; trichoscopic improvement; quality of life; psychological impact; efficacy in eyebrows, eyelashes, and nails; and safety profile. A total of 102 patients were included. At week 24, 40.2% of patients achieved SALT ≤ 20, with a greater response in adolescents (48.6%) than in adults (21.9%). The mean SALT score decreased from 86.2 ± 18.5 to 40.8 ± 37.1. Significant improvements were observed in trichoscopic signs and quality of life. The treatment was also effective on eyebrows, eyelashes, and nails. Adverse events were mild (e.g., acne, headache). Ritlecitinib had to be discontinued in only one case of severe anaemia. In this multicentre real-world study, ritlecitinib 50 mg/day was an effective and well-tolerated treatment option for severe alopecia areata. Alopecia areata is a common autoimmune disease that causes hair loss on the scalp and other parts of the body, such as eyebrows, eyelashes, and body hair. It affects people of any age, including adolescents, and often has a strong psycho-emotional impact, reducing quality of life. A new medication for severe alopecia areata, called ritlecitinib, was approved in 2023. Ritlecitinib is a Janus kinase inhibitor that modulates the immune response involved in the pathogenesis of the disease, promoting hair regrowth. However, data on its efficacy in everyday clinical practice have remained limited. To address this, we carried out a retrospective clinical study in Italy involving 20 university dermatology departments. We evaluated 102 adults and adolescents (≥ 12 years) with severe alopecia areata, treated with ritlecitinib 50 mg/day for 24 weeks. After 6 months of treatment, about 40% of patients had major hair regrowth on the scalp (with 80% of the scalp covered by hair). The treatment worked better in adolescents than in adults (48.6 vs 21.9%). Significant improvements were also noted in eyebrows, eyelashes, nail involvement, and quality of life parameters. Ritlecitinib was generally safe and well tolerated. Adverse effects were mild, and only one patient stopped treatment because of anaemia. Overall, our study showed that ritlecitinib was an effective and safe treatment for severe alopecia areata in real-world practice, particularly among adolescents.
Background Performance of artificial intelligence (AI)-based fracture detection is often evaluated on test sets that may not reflect real-world practice and overestimate AI accuracy, limiting clinical usability. Purpose To evaluate the impact of test set composition on the performance of AI models used for automated pediatric fracture detection at radiography. Materials and Methods This retrospective study analyzed pediatric appendicular trauma radiographs. Training and validation sets used consecutive radiographs, while two internal test sets were created: a "difficult" set containing radiographs with discrepancies between initial and final assessments and a "matched" set selected based on age, body region, and fracture presence. Three pediatric radiologists independently rated images for diagnostic difficulty and image quality. Sets were evaluated by EfficientNet (classification) and You Only Look Once, version 8 (YOLOv8) (object detection), models trained and validated on radiographs. Statistical significance was assessed with generalized estimating equations and odds ratios (ORs). Results A total of 39 703 pediatric patients were included (median age, 10.4 years [IQR, 6.3-13.3 years]; 56% [22 079 of 39 703] male). The difficult internal test set (392 patients, 786 radiographs) was associated with a 40% decrease in odds of a correct classification compared with the matched internal test set (526 patients, 786 radiographs) for EfficientNet variants (OR, 0.60 [95% CI: 0.53, 0.68]; P < .001). For YOLOv8 variants, difficult images were associated with an 80% decrease in odds of successful detection (OR, 0.20 [95% CI: 0.17, 0.25]; P < .001). Sensitivity analysis confirmed that images from the difficult set were rated as more challenging by experts than the "matched" set, and the difficult set contained more "complex" images (15% [119 of 786] vs 5% [41 of 786]) and fewer "simple" images (49% [381 of 786] vs 70% [550 of 786]) (P < .001). Conclusion AI performance in pediatric fracture detection was influenced by test set composition and radiograph complexity, where an internal test set of complex radiographs was associated with decreased odds of correct prediction. © RSNA, 2026 Supplemental material is available for this article.
Traumatic brain injury (TBI) is a leading cause of disability and death in children. More than 30% of children presenting to the emergency department (ED) with head trauma undergo brain computed tomography (CT), the standard neuroimaging modality in acute evaluation of intracranial pathology. Conventional magnetic resonance imaging (MRI) provides a non-ionizing alternative with greater sensitivity for certain intracranial injuries but is infrequently used in acute TBI because of limited scanner access and longer scan duration. Rapid brain MRI protocols reduce scan time and can be completed without sedation, with diagnostic accuracy for TBI comparable to CT, yet real-world availability remains limited. Point-of-care, low-field MRI (POC LF-MRI) systems are a recent radiologic advance that are portable, require less infrastructure, and allow bedside neuroimaging, including in critically injured children who cannot be safely transported. However, critical knowledge gaps exist regarding the diagnostic accuracy and feasibility of POC LF-MRI for pediatric head trauma in emergency and critical care settings. Our research aims to (1) determine the accuracy of POC LF-MRI for neuroradiographic TBI and clinically important TBI compared to current clinical standard of care initial neuroimaging, (2) determine the accuracy of POC LF-MRI for neuroradiographic injury progression on repeat neuroimaging, and (3) determine feasibility metrics and balancing measures of POC LF-MRI, including order-to-scan time, scan duration, proportion of incomplete scans, and ED length-of-stay. We will conduct a prospective, single-center, observational diagnostic accuracy cohort study of children 7-17 years old with blunt head trauma who undergo standard-of-care neuroimaging. Children with MR-unsafe implants or metallic shrapnel and wards of the state will be excluded. POC LF-MRI will be obtained within a reasonable time window of clinical neuroimaging, with a flexible window up to 72 hours, either in the ED, inpatient unit, or intensive care unit (ICU). The primary outcome is neuroradiographic TBI, defined as any traumatic intracranial finding on neuroimaging. Secondary outcomes include clinically important TBI (defined as TBI-related neurosurgical intervention, endotracheal intubation >24 hours, death, or ≥2-night hospitalization) and neuroradiographic injury progression on repeat neuroimaging (yes/no). Feasibility outcomes include order-to-scan time, scan duration, proportion of incomplete scans, and ED length of stay, along with other operational and balancing measures. Accuracy will be determined using imaging-level analyses comparing POC LF-MRI with clinical standard-of-care neuroimaging, reporting sensitivity, specificity, predictive values, and likelihood ratios with 95% confidence intervals for neuroradiographic TBI, clinically important TBI, and neuroradiographic injury progression, including predefined non-inferiority criteria for sensitivity, subgroup analyses, descriptive analyses of feasibility metrics, and exploratory analyses addressing incomplete imaging and missing data. The project was funded in 2024, and enrollment will be completed in July 2026. Data analyses are expected to be completed by December 2026, and the primary study results will be submitted for publication in 2027. This study will evaluate accuracy and feasibility for POC LF-MRI in an important subset of pediatric trauma patients and will provide preliminary data to inform future multicenter studies evaluating POC LF-MRI for children with head trauma.
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.
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.
Emergency abdominal surgeries (EASs) in children are often necessary to address life-threatening congenital and acquired conditions. This study aimed to determine short-term outcomes and predictors of in-hospital mortality after EAS in children at Mbarara Regional Referral Hospital (MRRH), South-Western Uganda. This prospective study was conducted from June to September 2024 and included children aged 0-17 years who underwent EAS at MRRH. Outcomes measured were 30-day in-hospital mortality, complications, and length of hospital stay. Overall survival after EAS was plotted using Kaplan-Meier curves. Cox regression analysis was used to determine predictors of in-hospital mortality after EAS. The 30-day mortality rate for all pediatric abdominal surgery was 152 per 10 000 person-days of hospitalization. Among 96children who required EAS at MRRH, the risk of death was significantly increased in those who had hypoxemia (adjusted hazard ratio (aHR) 12.4, p=0.011) and hypokalemia (aHR 5.02, p=0.044). Forty-one patients (42.7%) developed postoperative complications, the most common being surgical site infection (14.58%) and pneumonia (5.2%). The 30-day mortality rate after pediatric EAS in our setting is high and children who present with hypokalemia and hypoxemia are at increased risk of mortality after EAS.
Allergic rhinitis (AR) is one of the most prevalent chronic conditions in children and adolescents, significantly impacting quality of life and scholastic performance. Effective management requires therapeutic approaches that address the complex pathophysiology while ensuring safety and tolerability. This paper reviews the evidence supporting azelastine-fluticasone combination intranasal therapy in pediatric allergic rhinitis, with a focus on efficacy, safety, and clinical implementation. This paper encompassed clinical trials, guidelines (ARIA), consensus statements (SIAIP Delphi Consensus), and real-world evidence gathered from Italian primary care pediatricians managing children and adolescents with AR. Azelastine-fluticasone combination therapy demonstrates superior efficacy compared to monotherapy, exhibiting a rapid onset of action (15-30 min) and sustained symptom control. Its dual mechanism effectively addresses both early-phase (H1-receptor antagonism) and late-phase (glucocorticoid anti-inflammatory effects) allergic responses. Clinical trials conducted in adolescents aged 12-18 years confirm an excellent safety profile, with no significant effects observed on growth or the Hypothalamic-Pituitary-Adrenal (HPA) axis. Emerging evidence further may support its potential utility in younger children aged 6-12 years. The SIAIP Delphi Consensus on AR management, involving 42 pediatricians, achieved over 80% agreement on key management principles, particularly emphasizing the control of type 2 inflammation. Survey data collected from 864 Italian primary care pediatricians, collectively managing 81,231 children, indicates high adherence to ARIA guidelines (exceeding 70%) and a notable increase in the adoption of combination therapy, reaching up to 20% of cases. Azelastine-fluticasone combination intranasal therapy represents a significant paradigm shift in pediatric allergic rhinitis management. It offers superior efficacy, an excellent safety profile, and practical advantages that foster better treatment adherence. This therapeutic approach is well-aligned with contemporary guidelines and is increasingly being adopted in clinical practice for the management of moderate to severe AR in children and adolescents.
Breast cancer is a leading cause of mortality and morbidity among females worldwide. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we provided an updated comprehensive assessment of the epidemiological trends, disease burden, and risk factors associated with breast cancer globally, regionally, and nationally from 1990 to 2023. Breast cancer incidence, mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) were estimated by age and sex for 204 countries and territories from 1990 to 2023. Mortality estimates were generated using GBD Cause of Death Ensemble models, leveraging data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Mortality-to-incidence ratios were calculated to derive both mortality and incidence estimates. Prevalence was calculated by combining incidence and modelled survival estimates. YLLs were established by multiplying age-specific deaths with the GBD standard life expectancy at the age of death. YLDs were estimated by applying disability weights to prevalence estimates. The sum of YLLs and YLDs equalled the number of DALYs. Breast cancer burden attributable to seven risk factors was examined through the comparative risk assessment framework. The GBD forecasting framework was used to forecast breast cancer incidence and mortality from 2024 to 2050. Age-standardised rates were calculated for each metric using the GBD 2023 world standard population. In 2023, there were an estimated 2·30 million (95% uncertainty interval [UI] 2·01 to 2·61) breast cancer incident cases, 764 000 deaths (672 000 to 854 000), and 24·1 million (21·3 to 27·5) DALYs among females globally. In the World Bank low-income group, where a low age-standardised incidence rate (ASIR) was estimated (44·2 per 100 000 person-years [31·2 to 58·4]), the age-standardised mortality rate (ASMR) was the highest (24·1 per 100 000 [16·8 to 31·9]). The highest ASIR was in the high-income group (75·7 per 100 000 [67·1 to 84·0]), and the lowest ASMR was in the upper-middle-income group (11·2 per 100 000 [10·2 to 12·3]). Between 1990 and 2023, the ASIR in the low-income group increased by 147·2% (38·1 to 271·7), compared with a 1·2% (-11·5 to 17·2) change in the high-income group. The ASMR decreased in the high-income group, changing by -29·9% (-33·6 to -25·9), but increased by 99·3% (12·5 to 202·9) in the low-income group. The increase in age-standardised DALY rates followed that of ASMRs. Risk factors such as dietary risks, tobacco use, and high fasting plasma glucose contributed to 28·3% (16·6 to 38·9) of breast cancer DALYs in 2023. The risk factors with a decrease in attributable DALYs between 1990 and 2023 were high alcohol use and tobacco. By 2050, the global incident cases of breast cancer among females were forecast to reach 3·56 million (2·29 to 4·83), with 1·37 million (0·841 to 2·02) deaths. The stable incidence and declining mortality rates of female breast cancer in high-income nations reflect success in screening, diagnosis, and treatment. In contrast, the concurrent rise in incidence and mortality in other regions signals health system deficits. Without effective interventions, many countries will fall short of the WHO Global Breast Cancer Initiative's ambitious target of achieving an annual reduction of 2·5% in age-standardised mortality rates by 2040. The mounting breast cancer burden, disproportionately affecting some of the world's most vulnerable populations, will further exacerbate health inequalities across the globe without decisive immediate action. Gates Foundation, St Jude Children's Research Hospital.
To evaluate the mid-term outcomes of mechanical valve replacement of the common atrioventricular valve (CAVV) in single-ventricle pediatric patients and compare this with valvuloplasty. We conducted a retrospective study of 91 single-ventricle pediatric patients who underwent CAVV surgery between 2014 and 2025. Patients were divided into two groups according to the initial surgery: valvuloplasty and mechanical valve replacement groups. Baseline and perioperative characteristics were compared between groups. Overall survival and freedom from reintervention were analyzed using Kaplan-Meier curves. Receiver operating characteristic (ROC) curve analysis and maximally selected rank statistics were used to determine the optimal cut-off values for cardiopulmonary bypass (CPB) and aortic cross-clamp (ACC) time in predicting in-hospital and late mortality. There were 78 cases in valvuloplasty and 13 cases in the mechanical valve replacement group. The replacement group had significantly longer CPB and ACC time (p<0.001). In-hospital mortality was 2 out of 13 (15.4%) in the replacement group and 8 out of 78 (10.3%) in the valvuloplasty group (p>0.050). The median follow-up was 39 months. Kaplan-Meier analysis showed no significant difference in overall survival (p=0.280) and freedom from reintervention (p=0.270). Reintervention for recurrent regurgitation was required in eight patients after ventriculoplasty, whereas no reintervention was observed following valve replacement. ROC analysis identified a CPB time of 173.5 min as the optimal cut-off for predicting in-hospital mortality,with an area under the curve (AUC) of 0.751. Patients with CPB duration exceeding 180 min had significantly poorer survival (p=0.003). Mechanical valve replacement of the CAVV in single-ventricle pediatric patients provides satisfactory mid-term survival comparable to valvuloplasty, but with superior valve durability. Prolonged CPB time is associated with poorer survival and should be minimized whenever possible.
BACKGROUND: Although cardiac tumor in children are clinically rare, they present significant diagnostic challenges. This study aims to characterize the echocardiographic features of pediatric cardiac tumor and to correlate these findings with surgical and pathological results, thereby improving diagnostic accuracy. A further objective is to conduct long-term follow-up of surgical patients to provide insights into the prognosis and management of primary cardiac tumors in this population. METHODS: A retrospective analysis was conducted on pediatric patients under 18 years of age with cardiac tumor confirmed by both echocardiography and surgical pathology at our institution from January 2004 to January 2025. The inclusion criterion was confirmation of the lesion by both preoperative echocardiography and postoperative pathological analysis following surgical resection. Demographic and clinical data, including gender, age, clinical manifestations, and arrhythmias, were qualitatively summarized. Echocardiographic, surgical, and pathological findings were statistically analyzed. Long-term follow-up was performed to assess tumor recurrence, postoperative complications, and overall prognosis. RESULTS: Of the 18 pediatric patients included, 11 (61.1%) were symptomatic at presentation, with arrhythmias being the most common manifestation, observed in 9 (81.8%) of these symptomatic patients. Lesion size ranged from 0.4 to 10 cm, and the majority were solitary. Pathological analysis identified rhabdomyoma (n = 8, 44.4%), fibroma (n = 6, 33.3%), myxoma (n = 2, 11.1%), and cystic lesions (n = 2, 11.1%). The anatomical distribution varied by tumor type. Rhabdomyomas were most frequently found in the left ventricle (n = 2), with other locations including the right ventricle, right atrium, both ventricles, aortic valve, and superior vena cava (n = 1 each). All fibromas were predominantly located in the left ventricle (n = 5), with one case in the right atrium. The two myxomas were located in the right atrium and were multifocal with scattered distribution, respectively. The cystic lesions were located subaortic and on the posterior left ventricular wall (n = 1 each). A high concordance was observed between echocardiographic and pathological diagnoses, although discrepancies were noted in a subset of cases. CONCLUSION: This study confirms that primary cardiac tumor in children are predominantly benign, with rhabdomyoma and fibroma being the most common histological types. Clinical presentation is highly variable, with arrhythmias representing a frequent and significant symptom. While echocardiography serves as a reliable primary diagnostic tool, our findings highlight the potential for diagnostic discrepancies with histopathology, underscoring the need for careful interpretation. Ultimately, our data support a tailored approach to clinical management, where decisions on intervention are critically dependent on a comprehensive assessment of the tumor’s specific type, location, and size. This work provides valuable real-world data to enhance diagnostic accuracy and inform optimal management strategies for these rare conditions.
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The 2023 International Myositis Assessment and Clinical Studies Group (IMACS) guidelines introduced a standardized risk-stratification model for cancer screening in idiopathic inflammatory myopathies (IIM). However, real-world data on their application remain limited. This study aimed to evaluate the effectiveness of IMACS-based risk stratification in predicting malignancy and assess adherence to cancer screening recommendations in a multicentric Italian IIM cohort. We conducted a multicentre retrospective study including 411 IIM patients from five Italian rheumatology centres, classified into IMACS-defined standard, intermediate and high-risk groups. Cancer occurrence within three years of IIM diagnosis was assessed. Screening practices prior to the implementation of IMACS guidelines were compared with their recommendations. Logistic regression analysis was used to evaluate the predictive value of IMACS stratification. Among 411 patients, 180 (43.8%) were classified as high-risk, 156 (37.7%) as intermediate-risk and 75 (18.2%) as standard-risk. Cancer was diagnosed in 9.2% of patients within three years of IIM onset, with high-risk patients significantly more likely to develop malignancy (OR = 4.05, P = 0.026). Anti-TIF1γ (OR = 12.3, P < 0.001) and anti-SAE1 (OR = 11.9, P = 0.012) were independent predictors of cancer. Screening adherence varied, with underutilization of enhanced screening in intermediate-risk patients and a decline in screening over time. The IMACS stratification model effectively predicts cancer risk in IIM. However, real-world screening practices show inconsistencies, particularly in intermediate-risk patients. These findings support the need for optimized, risk-adapted malignancy surveillance in IIM and refinement of current guidelines based on real-world data.
This study aimed to characterize the metrics used to report Resource Utilization in Spine Healthcare (RUSH) for spine surgery patients in the United States. A systematic literature search identified studies related to resource utilization in spine surgery. Studies were excluded if the population was pediatric, outside the United States, or if patients received surgery for trauma, infection, or malignancy. There were 65 studies included in this analysis with a total of 941,231 patients. A total of 24 RUSH metrics were reported across all studies. The top 5 metrics were: length of stay (37/65), medical costs (33/65), medications (28/65), outpatient visits (26/65), and emergency department visits (26/65). Unique RUSH metrics used in <5 studies were: home health services (4/65), lab services (4/65), urgent care visits (4/65), referrals (4/65), nursing care (3/65), length of stay for future hospitalizations (2/65), electronic medical record messages (2/65), patient workdays lost (1/65), family member workdays lost (1/65), and insurance claims (1/65). Studies also varied in the number of metrics used as a proxy for RUSH. Across the studies, 9 used only 1 metric (14%), and 10 used only 2 metrics (15%). One study used 11 metrics (1.5%) and 2 studies used 13 metrics (3%). Spine surgery lacks consensus on the metrics used to report RUSH. While there are numerous metrics are used, there are no standardized guidelines to help researchers select these measures consistently across studies. Establishing a standardized set of RUSH metrics will enhance the ability to compare findings across studies, assess their validity, and correlate them with patient outcomes.
Road traffic collisions (RTCs) are the leading cause of death globally. Reducing the transportation time to definitive care and training bystanders in trauma management may impact clinical outcome. We aimed to study the impact of transportation methods on pediatric and adolescent severely injured vehicle occupants in Abu Dhabi Emirate, United Arab Emirates. The Abu Dhabi Trauma Registry prospectively collects data of all hospitalized trauma patients from seven major trauma centers in Abu Dhabi Emirate. We have studied all severely injured (ISS ≥ 12) road traffic collision patients, who were less than 19 years old (January 2014 to December 2023). Demography and clinical outcome of those transported by ambulance (n = 466) were compared with those transported by private vehicles (n = 47). Univariate analysis showed that patients who were transferred by private vehicles were significantly younger, (median (IQR range) age: 12 (6-15) years compared with 15.5 (12-17) years, p < 0.001), stayed significantly longer in the Emergency Department (median (IQR range) 275 (186-333) minutes compared with 214 (135-299) minutes, p = 0.01), were admitted significantly less to the ICU (31.9% compared with 51.9%, p = 0.009); and had significantly less hospital stay (median (IQR range) 3.5 (1-8) days compared with 7 (3-14) days, p = 0.003). There was no significant difference in mortality between the two groups (2.1% compared with 6.7%, p = 0.34). Logistic regression showed that mode of arrival did not significantly affect ICU admission (p = 0.26). The most significant factors that affected ICU admission were GCS, p < 0.001, OR 0.66 (95% CI 0.57-0.77) and ISS, p < 0.001, OR 1.12 (95% CI 1.08-1.16). A general linear model showed that GCS (p = 0.022) and RTS (p = 0.006) significantly affected length of hospital stay while mode of arrival did not (p = 0.38). Private vehicles appear to be safe for the transportation of selected major trauma children and adolescents with no adverse effects on ICU admission, hospital stay, or mortality. The role of bystanders in prehospital management and transportation of RTC victims should be further investigated.
BACKGROUND: Hyponatremia is common in critically ill children, and may be triggered by trauma-related stress responses. However, its clinical impact in pediatric trauma remains poorly defined. In this study, we investigated the incidence, risk factors, and outcomes of hyponatremia in pediatric patients with trauma. METHODS: This retrospective observational study investigated patients younger than 19 years admitted to a level I trauma center between 2016 and 2024 who had at least two serum sodium measurements during hospitalization. Patient demographic/anthropometric characteristics and trauma-related data were retrieved. Subsequently, demographic and admission/resuscitation characteristics were compared between patients with and without hyponatremia to investigate the epidemiology and risk factors of hyponatremia. RESULTS: Of 469 patients, 166 (35.4%) developed hyponatremia. In multivariable logistic regression analysis, very severe injury (ISS ≥ 25), surgical intervention, and early transfusion were identified as independent risk factors for hyponatremia. After adjustment for confounding variables, hyponatremia was independently associated with longer hospital stay, prolonged ICU stay, and increased duration of mechanical ventilation. CONCLUSIONS: Hyponatremia affects over one-third of pediatric patients with trauma and is strongly associated with injury severity and increased resource utilization. Early recognition of hyponatremia may help identify high-risk pediatric trauma patients and support optimized supportive care.
Developmental dysplasia of the hip remains a preventable yet underdiagnosed condition. Conventional screening strategies that rely on physical examination demonstrate limited sensitivity and fail to achieve comprehensive population coverage. Although universal ultrasound screening has shown promise, evidence supporting scalable, sustainable, and nurse-led community-based implementation models within real-world public health systems remains limited. To evaluate a nurse-led community-based ultrasound hip screening program integrated into routine maternal and child health services in Japan using the Reach, Effectiveness, Adoption, Implementation, Maintenance framework. A prospective cohort study with a mixed-methods design. Three rural Japanese municipalities (February 2024 to August 2025). Public health nurses, midwives, infants, and their caregivers who underwent routine newborn home visits or child-rearing consultations in the participating municipalities. The existing maternal and child health services evaluated across the following dimensions: Reach (coverage rate); Effectiveness (the proportion and mean age of infants referred early to medical institutions, and caregiver-reported outcomes following referral); Adoption (nurse adoption rate); Implementation (the proportion of ultrasound images meeting Graf's criteria, examination time, operational challenges, and cost); and Maintenance (continuation and policy integration). Ultrasound images were uploaded to a secure encrypted cloud server and interpreted remotely by Graf-certified pediatric orthopedic surgeons, with structured feedback provided to nurses throughout the implementation process. A total of 818 examinations were performed in 349 infants. The estimated coverage rate was 95.6%, indicating a near-universal range. Standard-plane images meeting Graf's criteria were obtained in 85.8% of examinations. Non-Type I hips accounted for 8.7% of cases, and 7.0% of infants were referred for further evaluation. Of these referred infants, 97.6% visited medical institutions, 54.8% required continued follow-up, and 4.8% required treatment. Adoption was high, with 95.5% of trained nurses conducting screenings. Implementation challenges included infant positioning, data-upload errors, and limited digital integration; however, interprofessional feedback from orthopedic surgeons improved technical performance. Ultrasound visualization enhanced caregiver understanding and facilitated timely adherence to referral recommendations. All municipalities continued screening, demonstrating strong maintenance. Nurse-led ultrasound hip screening can be feasibly integrated into routine maternal and child healthcare systems. This model enables early identification of suspected developmental dysplasia of the hip without clinical signs, and offers an equitable approach in resource-limited settings from a precision public health nursing perspective. University Hospital Medical Information Network Clinical Trial Registry; UMIN000051929 (https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000059248). Registration date: September 16, 2023. Start of recruitment: November 01, 2023. Nurse-led community ultrasound hip screening achieved 95.6% coverage, and 8.7% of the screened infants had a suspected dislocation or hip dysplasia.
PURPOSE: To evaluate the predictive performance of the Simple Stone Score (SSS) in pediatric percutaneous nephrolithotomy (PCNL) and compare it with the Stone-Kidney Size (SKS) score, developed specifically for this population. METHODS: Data from 145 consecutive pediatric patients who underwent PCNL between January 2008 and January 2024 were retrospectively analyzed. The SSS, based on largest stone diameter (LSD) and calyceal stone distribution (CSD), was applied. LSD was categorized as < 30 mm, 30–40 mm, or > 40 mm. CSD was classified as Grade I (single calyx or renal pelvis), Grade II (extension into one additional calyx), or Grade III (more than two calyces or complete staghorn stones). Residual fragments < 4 mm were considered clinically insignificant (CIRFs), and both stone-free and CIRF cases were defined as treatment success. The predictive performance of SSS for post-PCNL stone-free status was evaluated. RESULTS: The overall stone-free rate (SFR) was 68.3%, which increased to 74.5% when CIRFs were considered. On multivariate analysis, prior open stone surgery (p = 0.019), previous PCNL (p = 0.001), stone location (p = 0.011), and SSS (p = 0.008) were identified as independent predictors of SFR. Regarding treatment success, previous PCNL (p = 0.004), stone location (p = 0.020), and SSS (p = 0.003) remained significant independent predictors. Receiver operating characteristic curve analysis demonstrated no significant difference between the predictive performance of the SSS and SKS systems. However, decision curve analysis indicated that the SSS model offered a more consistent net clinical benefit. CONCLUSION: This study shows that the SSS is a reliable tool for predicting stone-free status in pediatric PCNL patients, comparable to the SKS and validated for this population.