Search Results (366)

Background: Myopia is projected to affect 50% of the global population by 2050. Its progression increases the risk of severe ocular pathologies, making it imperative to validate safe and effective non-pharmacological prevention interventions. Aim: To evaluate the clinical efficacy of low-level red-light therapy (RLRL) and nutritional supplementation in preventing and controlling myopia progression in children and adolescents. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (CRD420261301596). Randomized clinical trials in pediatric populations (aged 0–18 years) were included. The primary quantitative outcome measures for myopia were axial length (AL) and spherical equivalent (SE). Risk of bias (RoB 2) and heterogeneity (I²) were assessed. Results: 18 articles were included (n = 2438). RLRL demonstrated a significant reduction in axial elongation (mean difference (MD): −0.26 mm; 95% CI: −0.34 to −0.18) and a protective effect on refractive progression (MD: +0.60 D; 95% CI: 0.42 to 0.78), although with high heterogeneity (I² > 97%). Nutritional supplementation exhibited a modest, non-significant effect on axial length (−0.22 mm; 95% CI: −0.44 to 0.00), acting primarily as functional support. Conclusions: RLRL slows ocular elongation and myopia progression. Recent studies provide reassuring evidence regarding its long-term safety when recommended treatment protocols are followed. However, the high heterogeneity among studies, the need for standardized treatment discontinuation strategies, and the limited long-term evidence in geographically and ethnically diverse pediatric populations warrant further investigation. Current evidence is insufficient to demonstrate a consistent clinically meaningful effect of nutritional supplementation on axial elongation. Full article

Intranasal corticosteroids (INCS) remain the cornerstone of pharmacologic treatment for allergic rhinitis (AR) because of their well-established anti-inflammatory efficacy and generally favorable benefit–risk profile. Nevertheless, concerns regarding local and systemic corticosteroid-related adverse events (AEs) continue to influence patient adherence, prescribing practices, and long-term treatment acceptance. In routine clinical practice, safety perception and corticosteroid-related concerns frequently influence adherence and formulation selection to a greater extent than differences in clinical efficacy, particularly in pediatric populations and in patients requiring prolonged continuous therapy. Differences in pharmacokinetic and pharmacodynamic properties, including systemic bioavailability, glucocorticoid receptor affinity, lipophilicity, protein binding, and extent of first-pass metabolism, are considered important safety profile determinants of currently available INCS formulations. Available evidence indicates that local AEs, particularly epistaxis, nasal irritation, dryness, and sensory discomfort, represent the most frequently reported treatment-related AEs across INCS formulations, although these events are generally mild, self-limiting, and infrequently treatment-limiting. Clinically significant structural nasal complications, including septal perforation or progressive mucosal injury, appear uncommon in currently available studies. Systemic AEs, including hypothalamic–pituitary–adrenal (HPA) axis suppression, ocular toxicity, growth impairment, or clinically meaningful effects on bone metabolism, have not been consistently demonstrated with currently used low-systemic-exposure formulations administered at recommended therapeutic doses. Although systemic glucocorticoid exposure has been associated with alterations in lipid metabolism, adipose tissue function, and metabolic homeostasis, currently available intranasal corticosteroids demonstrate minimal systemic exposure, making clinically relevant metabolic effects unlikely under recommended therapeutic conditions. Formulations such as mometasone furoate, fluticasone propionate, fluticasone furoate, and ciclesonide exhibit pharmacokinetic characteristics associated with minimal systemic exposure because of extensive first-pass metabolism and low oral bioavailability. Although substantial pharmacokinetic differences exist between currently available INCS formulations, direct comparative evidence demonstrating clinically meaningful superiority in systemic safety outcomes remains limited. Current evidence suggests that formulation-dependent differences are clinically more relevant with respect to local tolerability, sensory characteristics, patient preference, and long-term adherence than major systemic safety outcomes. Pediatric evidence is generally reassuring, although historical concerns regarding growth suppression associated with earlier corticosteroid formulations continue to influence clinical practice. Currently available evidence supports the use of modern INCS as effective and generally well-tolerated therapeutic options across adult and pediatric populations. Full article

Background: Heritable thoracic aortic disease (HTAD) encompass a heterogeneous spectrum of conditions characterized by increased susceptibility to developing thoracic aortic aneurysm and life-threatening complications, including aortic dissection and rupture. Despite distinct underlying mechanisms involving extracellular matrix integrity, vascular smooth muscle cell function, and dysregulation of signaling pathways, these disorders converge on a shared vulnerability of the aortic wall. Although acute events typically occur in adulthood, the disease process often begins early in life, making HTAD highly relevant in pediatric practice, where early recognition and longitudinal management are essential. Aims: This narrative review provides a biology- and genetics-oriented, translational complement to current consensus recommendations, framing pediatric HTAD as a developmentally shaped disorder of the aortic wall in which genotype increasingly informs diagnosis, surveillance, and treatment. Methods: Relevant studies were identified through a comprehensive PubMed search, with particular focus on pathogenic mechanisms, current clinical guidelines, follow-up strategies and emerging genetic perspectives. Results: Genetic testing is emerging as a key tool for the management of HTAD, although its clinical utility remains limited by provisional genotype–phenotype correlations and inconclusive results. Current risk stratification is still mainly based on aortic diameter surveillance, while pharmacological strategies are predominantly extrapolated from Marfan syndrome trials, highlighting important gaps in evidence. Conclusions: Genetic advances are expanding management opportunities in HTAD, but their clinical translation remains challenging. Disease-specific risk models integrating genetic and clinical data may improve individualized risk stratification, treatment strategies and clinical outcomes. Full article

Pediatric phlebotomy is a common invasive procedure frequently associated with pain, anxiety, and fear, which may negatively affect children’s cooperation and overall healthcare experiences. Virtual reality (VR) has emerged as a promising non-pharmacological intervention capable of providing immersive distraction and emotional engagement during painful medical procedures. The aim of this systematic review was to evaluate the effectiveness of immersive VR in reducing pain perception and anxiety-related outcomes among pediatric patients undergoing phlebotomy procedures. This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The research question was developed using the PICO framework. Randomized controlled trials and comparative controlled studies published between January 2020 and September 2025 were identified through systematic searches of PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL). Studies involving children and adolescents aged 4–17 years undergoing phlebotomy or venipuncture procedures were eligible for inclusion. A total of six studies comprising 557 pediatric participants were included in the review. The VR interventions involved immersive and interactive environments, including educational simulations, animated scenarios, and game-based experiences delivered through head-mounted displays. Four studies reported statistically significant reductions in pain and/or anxiety among participants exposed to VR compared with control groups, whereas two studies found no significant differences. Across the included studies, VR interventions were generally well accepted by children, parents, and healthcare professionals, with only mild and transient adverse effects reported. However, substantial heterogeneity was observed regarding clinical settings, VR technologies, intervention protocols, and outcome assessment methods. The current evidence suggests that immersive VR is a promising adjunctive strategy for reducing pain and anxiety during pediatric phlebotomy procedures. Nevertheless, the available evidence remains limited by methodological heterogeneity and relatively small sample sizes. Future research should focus on larger, well-designed randomized controlled trials using standardized intervention protocols and outcome measures to support evidence-based implementation of VR in pediatric clinical practice. Full article

Apnea of prematurity (AOP) remains a critical challenge in neonatal care, with caffeine citrate serving as the cornerstone of pharmacological intervention. However, the current standardized dosing schedule fails to account for significant inter-individual variability in caffeine pharmacokinetics and clinical response. This narrative review explores the transformative potential of integrating wearable sensor technologies and multi-modal data analytics into a closed-loop framework for personalized caffeine therapy. Based on a synthesis of current monitoring literature, we propose a theoretical, comprehensive monitoring system utilizing the area under the respiratory curve (rAUC) as a continuous proxy metric, alongside waveform amplitude analysis aligned with pediatric polysomnography standards. By incorporating emerging metrics such as respiratory rate variability (RRV) and hypoxic burden, the framework enables the objective quantification of respiratory stability. Furthermore, the integration of established neonatal intensive care unit (NICU) parameters for bradycardia and oxygen saturation detection provides a critical cross-validation layer to minimize artifact-induced false alarms. This conceptual model bridges the gap between advanced signal processing and clinical oversight, offering a scalable pathway toward precision dosing. By shifting from reactive to predictive neonatology, sensor-driven optimization can enhance therapeutic efficacy, reduce alarm fatigue, and ultimately improve developmental outcomes for preterm infants. Full article

Background: Congenital heart defects (CHD) are the most common congenital malformations and often require complex, lifelong pharmacotherapy. In pediatric CHD populations, multidrug regimens targeting cardiac function and comorbidities predispose patients to polypharmacy. At the molecular level, concomitant drug use increases the risk of pharmacokinetic and pharmacodynamic interactions. Methods: This study aimed to characterize medication patterns and assess polypharmacy and potential drug–drug interactions in patients with CHD. A cross-sectional online survey was conducted in collaboration with the German National Register for Congenital Heart Defects (NRCHD) between November and December 2021. Patients aged 6–17 years with CHD were eligible for inclusion. Participants reported their current medications in open-ended questions. Drugs were categorized into pharmacological classes, and common drug combinations were evaluated for potential interactions. Results: Of 894 participants included in the analysis, 372 reported current medication use. Among these, 179 (48.1%) met criteria for polypharmacy (≥2 drugs). Polypharmacy was more frequent in patients with higher disease severity and comorbidity burden. Several drug combinations showed potential for clinically relevant pharmacokinetic and pharmacodynamic interactions, including mechanisms involving renal electrolyte handling, altered protein binding, cytochrome P450-mediated metabolism, and additive pharmacodynamic effects. Conclusions: Children with CHD are exposed to complex multidrug regimens with a considerable interaction risk, underscoring the need for systematic medication review and mechanistically informed pharmacological management in pediatric CHD care. Full article

Pediatric drug therapy remains fundamentally challenged by profound interindividual variability driven by dynamic development, genetic, and environmental factors. Although dosing strategies based on age, body weight, or body surface area remain important starting points in pediatric pharmacotherapy, they may not fully capture ontogeny-dependent variability in drug disposition and response. Consequently, clinically relevant differences in efficacy and toxicity may still occur among children receiving similar weight-adjusted doses. Pharmacogenomics offers a promising framework for individualized therapy; however, its clinical translation in pediatrics is limited by developmental variability in gene expression and enzyme activity. Emerging evidence highlights the pivotal role of epigenetic regulation, including DNA methylation, histone modifications, and microRNAs, in modulating pharmacogenetic expression across developmental stages, thereby reshaping drug response trajectories. Concurrently, advances in artificial intelligence and next-generation sequencing enable integration of multidimensional datasets, facilitating predictive modeling of drug efficacy and toxicity. This narrative review provides a comprehensive synthesis of developmental pharmacology, pharmacogenomics, and epigenetic mechanisms, while critically evaluating current translational gaps and implementation challenges. Importantly, it proposes an integrative precision framework that incorporates genetic, epigenetic, and computational insights to optimize pediatric pharmacotherapy. By bridging mechanistic biology with emerging digital health technologies, this work advances a paradigm shift from empirical prescribing toward predictive, adaptive, and individualized therapeutic strategies. The proposed approach holds significant potential to enhance clinical outcomes, minimize adverse effects, and accelerate the realization of precision medicine in pediatric populations. Full article

Background/Objectives: Pregnant and breastfeeding people require special considerations for enrollment in clinical trials. However, the baseline proportion of cardiovascular clinical trials including pregnant and breastfeeding people remains unclear. The objective of this study was to characterize the representation of pregnant and breastfeeding people in cardiovascular randomized clinical trials (RCTs) and to determine whether inclusion has increased following the 2018 removal of pregnancy from the FDA’s “vulnerable population” designation. Methods: We screened eight high-impact general medicine and specialty journals for cardiovascular RCTs published between 1 January 2019 and 31 December 2023. We included RCTs examining pharmacological, behavioral, educational, device, or procedural interventions. We excluded RCTs that recruited exclusively male, pediatric, geriatric, or postmenopausal populations, and those specifically designed for obstetrical populations. We also excluded publications reporting follow-up or subgroup, pooled, or secondary analyses of previously published trials. Data from RCTs were independently extracted in duplicate following the PRISMA guidelines. We examined each RCT for pregnancy and breastfeeding inclusion criteria, rationale for exclusion, and contraception requirements. Results: Of 3764 citations identified, 586 met the inclusion criteria. In total, four (0.7%) RCTs permitted inclusion of pregnant people, 382 (65%) explicitly stated their exclusion, and 200 (34%) did not provide specific enrolment criteria for them. The few studies that explicitly stated exclusion of pregnant people (31/382, 8.1%) provided a rationale. 225 (38%) RCTs explicitly stated exclusion of breastfeeding people, and none explicitly permitted inclusion. There was no significant difference in the proportion of pregnant or breastfeeding people included or excluded from RCTs that began enrollment before 2018 versus after 2018. Conclusions: Pregnant and breastfeeding people are primarily excluded from cardiovascular RCTs, and the justification for their exclusion is rarely provided. Full article

The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide belonging to the calcitonin family, discovered as a product of alternative splicing of the calcitonin gene. CGRP has emerged as a pleiotropic signaling molecule with widespread distribution in the central and peripheral nervous systems, particularly within primary sensory neurons. This narrative review synthesizes current knowledge on the CGRP system, integrating recent advances in its molecular structure, gene organization, and post-translational processing with high-resolution structural insights into its heterodimeric receptor complex (CLR-RAMP1) obtained through cryo-electron microscopy. We also include long-term safety data on anti-CGRP monoclonal antibodies, emerging cardiovascular risk signals, and novel therapeutic applications in vestibular migraine and pediatric populations. The intracellular signaling cascades activated by CGRP, including the canonical cAMP-PKA pathway, MAP kinase activation, and context-dependent calcium signaling, are discussed in relation to its diverse physiological functions. These encompass vasodilation, nociception modulation, neurogenic inflammation, gastrointestinal motility, bone metabolism, tissue regeneration, and energy homeostasis. The central role of CGRP in migraine pathophysiology is examined to understand the development of targeted therapies. The current pharmacological landscape is reviewed, including the evolution of small-molecule CGRP receptor antagonists (gepants) through three generations and the four approved monoclonal antibodies targeting CGRP or its receptor, with comparative analysis of their efficacy, safety profiles, and clinical positioning. Beyond migraine, emerging and predominantly preclinical roles of the CGRP system are discussed in chronic pain, osteoarthritis, cardiovascular diseases, sepsis, cancer (particularly bone metastases and tumor microenvironment immunomodulation), and neurodegenerative disorders such as Alzheimer’s disease. In these areas, the available evidence remains heterogeneous and, in most cases, is not yet sufficient to support clinical translation. Finally, future directions are discussed, including the development of stable CGRP analogs, allosteric modulators, and the potential expansion of therapeutic applications into oncology, intensive care medicine, and neuroprotection. Full article

Background/Objectives: Of the approximately 8% of children in the United States (US) with food allergy (FA), roughly 40% report allergy to multiple foods. The ubiquity and intensity of FA management can impose psychosocial burdens on both pediatric patients and caregivers, which may be exacerbated among those allergic to multiple foods. However, little work has comprehensively estimated the burden of multi-FA in heterogeneous pediatric populations with clinically confirmed FA. Methods: Children with allergist-diagnosed, IgE-mediated FA were enrolled in the FORWARD multisite prospective cohort study. Psychosocial burden was assessed annually using the FA Quality of Life Questionnaire-Parent Form 10 (FAQL-PF10) and FA Independent Measure-Parent Form (FAIM-PF); psychosocial burden for caregivers was measured with the FA Quality of Life-Parental Burden (FAQL-PB) Questionnaire. Multilevel regression models estimated independent effects of the number of current FAs after adjusting for child age, gender, race, ethnicity, household income, caregiver education, atopic comorbidities, and recruitment site. Results: FA-related psychosocial burden increased linearly for patients and caregivers with each additional FA even after controlling for demographic factors such as age, gender, race, ethnicity, income, education, and other atopic conditions, as well as repeated observations within participants: FAQL-PF10 B = 0.082 (N = 2206; p = 0.004), FAIM-PF B = 0.152 (N = 2206; p < 0.001), and FAQL-PB B = 0.166 (N = 1081; p < 0.001). Conclusions: The psychosocial burden of pediatric FA increases monotonically with each additional current FA, highlighting opportunities for tailored psychosocial, behavioral, and pharmacologic interventions to improve FA-related outcomes among those most impacted. Full article

Background/Objectives: Teratomas of the sacrococcygeal region are rare, but the most common tumors found in fetuses. They develop from the three germ layers—mesoderm, ectoderm, and endoderm—and occur at a rate of 1 in 27,000 to 1 in 40,000, with a fourfold higher incidence in female fetuses. 63.9–74% of sacrococcygeal teratomas are detected prenatally, most often in the second trimester. Methods: This study reports the case of a woman in her second pregnancy at 29 weeks and 2 days gestation who was incidentally diagnosed with tumor-like lesion in the sacrococcygeal region of fetus. The clinical situation required the pregnancy to be delivered by emergency cesarean section, and the tumor was surgically removed within the first few days of life. The lesion was finally diagnosed as an immature teratoma, and appropriate management was initiated, resulting in stabilization of the child’s general condition and proper development. Results: Detailed imaging and characterization of the lesion are essential for determining the appropriate management and minimizing foreseeable obstetric and neonatal complications. Fetal echocardiography in cases of suspected teratoma in the sacrococcygeal region is essential for identifying life-threatening risk factors and influences the planning of further management. The choice of treatment depends on the clinical situation; among intrauterine interventions and pharmacological therapy, it has been demonstrated that surgical removal of the lesion within the first days of life reduces the risk of recurrence. Conclusions: In any case where lesion such as tumor of the sacrococcygeal region of fetus is suspected, the pregnant woman should be managed at a tertiary care center to ensure multidisciplinary care involving obstetricians, neonatologists, pediatric surgeons, and oncologists. This study provides a review of the literature on methods of diagnosis and treatment of sacrococcygeal teratomas in fetuses. It emphasizes the importance of accurate diagnosis and prenatal care in such cases and their impact on further management. Full article

Inflammatory bowel disease (IBD) with an onset in childhood is characterized by a more extensive phenotype, a more aggressive clinical course, and a higher risk of long-term complications, including growth retardation, compared to adult-onset disease. While tumor necrosis factor-alpha (TNF-α) inhibitors are the cornerstone of therapy, achieving sustained remission in children is often hindered by unique pharmacokinetic challenges, such as accelerated drug clearance and a higher propensity for immunogenicity. This review explores the evolving role of therapeutic drug monitoring (TDM), specifically the paradigm shift from reactive to proactive strategies. While proactive TDM remains a subject of debate in adult IBD, emerging pediatric data strongly support its routine use to optimize treatment durability and prevent secondary loss of response. Evidence-based target trough concentrations for pediatric patients are critical for achieving mucosal healing: 8–13 µg/mL at week 6 and >5–7 µg/mL during maintenance for infliximab, and >13–14 µg/mL post-induction for adalimumab. Beyond clinical outcomes, this review emphasizes the economic viability of proactive TDM, which has been shown to reduce total healthcare expenditures by 18–30% by minimizing hospitalizations and avoiding premature treatment switches. By integrating pharmacological data with clinical pathways, proactive TDM serves as an essential tool for personalized medicine, ensuring safer and more cost-effective management of pediatric IBD. Full article

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for the treatment of type 2 diabetes (T2D), are increasingly used for the management of overweight and obesity in children and adolescents. However, the impact of concomitant lifestyle interventions, which vary in scope, structure, and intensity, remains unclear. Methods: A systematic search of PubMed, Scopus, and ClinicalTrials.gov was conducted from April to December 2025 (last update: 12 December 2025), in accordance with the PRISMA 2020 statement. Randomized and observational studies including patients aged 6–19 years with overweight or obesity, with or without T2D, treated with GLP-1 RAs or dual GIP/GLP-1 agonists, were included. Anthropometric outcomes, metabolic parameters, and the scope and structure of concomitant nutritional and behavioral interventions were assessed. Results: Fifteen studies (12 interventional [RCT/non-RCT] and 3 observational), including 1448 participants, were analyzed: liraglutide (n = 6), exenatide (n = 5), semaglutide (n = 1), dulaglutide (n = 1), tirzepatide (n = 1), and lixisenatide (n = 1). Intervention duration ranged from 6 to 68 weeks. Reported BMI reductions varied across studies and pharmacological agents, with semaglutide trials reporting reductions of up to −16.1%. Lifestyle interventions were heterogeneously reported, ranging from general dietary advice to structured, multidisciplinary programs including nutritional counseling, physical activity, and behavioral or family support. Due to heterogeneity in study design and reporting, the independent contribution of lifestyle interventions could not be determined. Conclusions: Available evidence suggests that GLP-1 RAs may represent an effective therapeutic option for children and adolescents with obesity and metabolic disorders. However, available evidence is largely derived from studies incorporating inconsistently reported lifestyle interventions, limiting the ability to disentangle pharmacological and lifestyle effects. Standardized reporting and studies specifically designed to assess their independent and combined effects are needed. Future research should standardize the reporting of lifestyle protocols (e.g., using TIDieR), incorporate validated measures of eating behavior, food preferences, and dietary intake, and use designs (e.g., factorial or stratified randomization of lifestyle intensity) that allow for the pharmacological and behavioral contributions to be quantified separately. This review highlights a critical and previously underexplored methodological gap regarding the structure and reporting of lifestyle co-interventions in pediatric GLP-1 trials. Full article

Background: Pediatric tuberculosis (TB) remains a major global health concern, accounting for a substantial proportion of TB-related morbidity and mortality worldwide. Treatment in children is particularly challenging due to age-specific pharmacokinetics, difficulties in drug administration, poor palatability, and reliance on caregivers for adherence. Objectives: This narrative review aims to evaluate the advantages and limitations of fixed-dose combinations (FDCs) in the treatment of pediatric TB, with a focus on adherence, pharmacological considerations, clinical outcomes, and implementation challenges. Methods: A narrative review of the literature was conducted, including clinical studies, pharmacokinetic analyses, programmatic data, and international guidelines related to the use of FDCs in pediatric TB management. Results: Evidence indicates that pediatric FDCs significantly improve treatment adherence by reducing pill burden and simplifying dosing regimens. They also decrease the risk of medication errors and inadvertent monotherapy, thereby contributing to the prevention of drug resistance. The availability of dispersible, child-friendly formulations has enhanced acceptability and ease of administration. However, limitations persist, including reduced flexibility in dose individualization, challenges in identifying the causative agent in adverse drug reactions, and variable access across settings. Pharmacokinetic concerns, particularly regarding rifampicin exposure, have been addressed in newer WHO-recommended formulations. Conclusions: FDCs represent a critical advancement in pediatric TB management and are strongly supported by international guidelines. Further research is needed to optimize formulations, ensure equitable access, and evaluate long-term clinical outcomes in diverse pediatric populations. Full article

Kawasaki disease (KD) represents the foremost cause of acquired pediatric heart disease, with coronary artery injury being the principal factor contributing to adverse prognoses. A significant clinical challenge is that 20–30% of patients demonstrate resistance to intravenous immunoglobulin (IVIG), which markedly elevates the risk of coronary artery lesions and long-term cardiovascular sequelae. Consequently, there is an urgent need to investigate novel pathogenic mechanisms beyond the conventional cytokine storm theory and to identify effective therapeutic targets. This review systematically summarizes the key role of the autophagy–inflammation axis in KD vasculopathy. Current evidence indicates that defective mitophagy and lysosomal dysfunction induce mitochondrial DNA release, resulting in overactivation of the NLRP3 inflammasome and cGAS-STING pathways, which amplify inflammatory responses and aggravate endothelial damage. The regulation of this axis is dynamic during both the acute and recovery phases and is influenced by metabolic reprogramming and epigenetic modifications, which may partially explain the lack of response to IVIG. Pharmacological agents, such as rapamycin and metformin, as well as natural compounds, such as resveratrol and urolithin A, have demonstrated beneficial anti-inflammatory effects in preclinical studies. Targeting the autophagy–inflammation axis represents a significant research direction with the potential to evolve into a promising therapeutic strategy. Mechanistically, restoring the balance of the autophagy–inflammation axis holds promise for mitigating coronary complications and improving long-term cardiovascular outcomes in children with KD; however, this prospect requires validation through prospective clinical studies. Full article