Pediatric Drugs最新文献

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most frequent periodic fever syndrome in non-Mediterranean children, usually manifesting before the age of 5 years. It is characterized by clockwork episodes of fever lasting 3-7 days, accompanied by aphthous stomatitis, pharyngitis, and/or cervical adenitis. Typically, patients with PFAPA are generally well between episodes and exhibit normal growth and development. Although PFAPA often resolves spontaneously, its recurrent nature can significantly impact quality of life, and symptoms may persist into adulthood. This narrative review aimed to consolidate current knowledge on PFAPA epidemiology, pathogenesis, clinical presentation, diagnostic considerations, and therapeutic options. A structured literature search was performed using PubMed, Cochrane Library, and Scopus, focusing on relevant articles specifically addressing PFAPA. Increasing evidence suggests multifactorial pathogenesis involving innate immune dysregulation, activation of the NLRP3 inflammasome, and Th1-driven inflammation. Genetic analysis studies suggest a polygenic inheritance of PFAPA, linking it to immune pathways shared with familial Mediterranean fever and Behçet's disease. Diagnosis remains clinical, though genetic testing may be warranted in specific cases. Management strategies vary owing to the absence of standardized guidelines. Oral corticosteroids are highly effective for acute episodes but may shorten the interval between flares. Among preventive therapies, colchicine appears to reduce attack frequency, although evidence of its efficacy is limited, while tonsillectomy is often considered curative but recommended for patients with refractory disease or when there is a concurrent otolaryngologic indication. Further research is needed to refine diagnostic criteria and optimize treatment strategies, ultimately improving patients' and caregivers' quality of life.

Kawasaki disease (KD) is a common pediatric vasculitis, with coronary artery lesions (CALs) representing its most severe complication. Early identification of high-risk patients, including those with disease resistant to first-line treatments, is essential to guide personalized therapeutic approaches. Given the limited reliability of current scoring systems, there has been growing interest in the development of new prognostic models based on machine learning algorithms and artificial intelligence (AI). AI has the potential to revolutionize the management of KD by improving patient stratification and supporting more targeted treatment strategies. This narrative review examines recent applications of AI in stratifying patients with KD, with a particular focus on the ability of models to predict intravenous immunoglobulin resistance and the risk of CALs. We analyzed studies published between January 2019 and April 2024 that incorporated AI-based predictive models. In total, 21 papers met the inclusion criteria and were subject to technical and statistical review; 90% of these were conducted in patients from Asian hospitals. Most of the studies (18/21; 85.7%) were retrospective, and two-thirds included fewer than 1000 patients. Significant heterogeneity in study design and parameter selection was observed across the studies. Resistance to intravenous immunoglobulin emerged as a key factor in AI-based models for predicting CALs. Only five models demonstrated a sensitivity > 80%, and four studies provided access to the underlying algorithms and datasets. Challenges such as small sample sizes, class imbalance, and the need for multicenter validation currently limit the clinical applicability of machine-learning-based predictive models. The effectiveness of AI models is heavily influenced by the quantity and quality of data, labeling accuracy, and the completeness of the training datasets. Additionally, issues such as noise and missing data can negatively affect model performance and generalizability. These limitations highlight the need for rigorous validation and open access to model code to ensure transparency and reproducibility. Collaboration and data sharing will be essential for refining AI algorithms, improving patient stratification, and optimizing treatment strategies.

Background: Fibro-adipose vascular anomaly (FAVA) is a rare and complex vascular malformation that, to date, has hardly been studied, especially in children. The diagnosis and management of FAVA is complicated, and no treatment guidelines have yet been published.

Objectives: This study aimed to analyze the clinical manifestations and diagnostic and genetic evidence of FAVA and to explore safe and effective treatment with sirolimus in pediatric patients.

Methods: We retrospectively analyzed the clinical manifestations and examination data of 18 pediatric patients with FAVA who presented at the Vascular Anomaly Center from September 2019 to February 2023 and summarized the basis on which a diagnosis of FAVA was made. A genetic examination was completed in five cases. A total of 12 cases were treated with oral sirolimus. We analyzed changes in skin lesions before and after treatment and recorded the occurrence of adverse reactions.

Results: Of the 18 patients, 15 were girls and 3 were boys. Most lesions (15 cases) were in the lower extremities, accompanied by varying degrees of chronic pain, functional impairment, contractures, and other functional disorders. Imaging findings can be divided into three categories: focal, focal infiltrative, and diffuse. Histopathological manifestations were malformed vascular fibro-adipose tissue. A genetic examination of five cases identified a PIK3CA somatic mutation. After oral sirolimus treatment, pain and dysfunction associated with the lesions were significantly improved, the lesion volume dramatically diminished, and no obvious adverse reactions occurred.

Conclusions: With the help of imaging, and histopathological and somatic genetic examinations, FAVA can be promptly diagnosed and treated to avoid serious dysfunction. The efficacy and safety of oral sirolimus in the treatment of FAVA deserves further study.

Ceftazidime/avibactam (CAZ/AVI) is effective against a wide range of carbapenem-resistant Enterobacterales and multidrug-resistant Pseudomonas. The European Medicines Agency (EMA) approved its use in children from 3 months of age for urinary tract (UTI) and intra-abdominal infections (IAI). Published data in children are limited. We performed a review of existing literature on the use of CAZ/AVI in children. Our search identified a phase I dose-exploratory trial, two registrational phase II clinical trials and nine real-world case series. The efficacy, adverse effects and pharmacokinetics of CAZ/AVI in children were summarized. We also describe the experience of the use of CAZ/AVI in a tertiary hospital in Madrid, Spain. Up to March 2023, 22 episodes of treatment with CAZ/AVI were recorded in 14 patients (50% female, with a median age of 4 years [interquartile range (IQR) 3.5-9]). UTI, bacteraemia or sepsis were the most common clinical conditions for which CAZ/AVI was prescribed. CAZ/AVI was started as targeted therapy in 10 paediatric patients and as empirical therapy in 12 (54.5%) children. The treatment indication was reviewed and adapted according to microbiological results by a paediatric infectious diseases team. Effectiveness of CAZ/AVI was adequate, and there were no discontinuations in any case because of adverse effects.

Background and objective: Nigella sativa is a widely used medicinal plant with several potential therapeutic uses. This study aimed to investigate the possible beneficial cardioprotective effect of Nigella sativa in pediatric patients with type 1 diabetes mellitus.

Methods: Sixty children and adolescents with type 1 diabetes were randomized into two groups: group I (n = 30) who received Nigella sativa seed oil 450 mg twice daily after meals for 3 months in addition to insulin, and group II (n = 30) who received insulin alone. Echocardiographic examinations were performed before and after the treatment. The lipid profile, malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, and troponin I were also measured before and after Nigella sativa treatment.

Results: After 3 months of Nigella sativa administration, group I had significantly lower cholesterol and low-density lipoprotein-cholesterol, malondialdehyde, nitric oxide, tumor necrosis factor-α, transforming growth factor-β, and troponin I levels compared with their pretreatment levels and compared with group II. In addition, group I had a significantly higher left ventricular E'/A' ratio and two-dimensional left ventricular global longitudinal strain (2D-LV GLS) compared with baseline values and compared with group II after treatment.

Conclusions: Nigella sativa can improve subclinical left ventricular dysfunction in pediatric patients with type 1 diabetes mellitus.

Clinical trial registration: this clinical trial was registered at www.pactr.org with ID: PACTR202302478939306.

The evidence to support the efficacy and safety of pharmacological treatments for chronic non-cancer pain in children is limited. In practice, clinicians are often required to establish therapeutic plans using data extrapolated from adult studies, which may not apply to younger patients. Recent systematic reviews and meta-analyses indicate minimal evidence of benefit for these treatments in children; however, the low quality of studies included in these reviews complicates the conclusions that can be derived from them. In this article, we focus on safety, an outcome as critical as efficacy in clinical trial design but often designated as secondary or even exploratory. Specifically, we examine methods for assessing adverse events in clinical research and propose a practical approach for evaluating these events in everyday practice. Additionally, we outline our strategy to conduct a risk-benefit analysis at the individual patient level, highlighting the importance of using a composite risk-benefit metric rather than assessing these outcomes separately. This approach enables real-time monitoring of both drug-related symptom relief and adverse effects, facilitating clinically meaningful risk-benefit discussions with patients and their families. Finally, we advocate for improvements in clinical trial design for pediatric chronic pain treatments, particularly around adverse events. Future trials should incorporate standardized definitions, comprehensive risk-benefit evaluations, and transparent outcome reporting. Implementing these changes may enhance decision-making by balancing the safety and the effectiveness of pharmacological treatments for children and adolescents with chronic pain.

Background: Nephrotoxicity may increase the risk of neonatal mortality. Early identification of risk factors for nephrotoxicity is essential to improve clinical outcomes. This study aimed to determine the risk factors for nephrotoxicity in neonates receiving vancomycin to promote the safe use of vancomycin.

Methods: We searched international and Chinese databases from 1990 to 24 March 2024 for studies involving neonates receiving vancomycin and reporting their nephrotoxic outcomes. Effects were estimated with 95% confidence intervals (CIs), odds ratios (ORs), and standardized mean differences. We evaluated the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool.

Results: In total, the study included 12 retrospective cohort studies involving 2079 neonates. In neonates receiving vancomycin, the incidence of nephrotoxicity varied from 2.7 to 20.0%. Moderate-quality evidence indicated that furosemide (OR 5.80; 95% CI 2.98-11.28), amphotericin B (OR 2.75; 95% CI 1.23-6.12), patent ductus arteriosus (OR 5.93; 95% CI 2.80-12.55), and necrotizing enterocolitis (OR 4.49; 95% CI 2.12-9.49) were risk factors for nephrotoxicity in neonates receiving vancomycin. Low-quality evidence suggested that vasoactive agents (OR 9.23; 95% CI 1.06-80.62) were risk factors. Subgroup analysis with moderate-quality evidence identified a steady-state vancomycin trough concentration > 20 mg·L^-1 (OR 6.87; 95% CI 3.81-12.39) as a risk factor. Very low-quality evidence indicated that aminoglycosides (OR 0.29; 95% CI 0.13-0.62) were not risk factors.

Conclusions: This study reveals the nephrotoxic risk factors for neonates receiving vancomycin, which could help in the implementation of measures to prevent further renal impairment.

Prospero registration number: CRD42024564584.

Pediatric asthma remains a prevalent and challenging chronic condition globally, affecting quality of life and imposing significant burdens on families and healthcare systems. Despite advancements in understanding asthma pathophysiology and treatment, key controversies persist in optimizing management strategies. Inhaled corticosteroids (ICS) are the cornerstone of treatment, reducing inflammation and preventing exacerbations. While concerns about growth suppression exist, evidence suggests that this effect is primarily associated with high doses and prolonged use, rather than standard maintenance therapy. Nonetheless, adherence to ICS remains suboptimal, necessitating strategies to ensure effective and sustained treatment. The introduction of maintenance and reliever therapy (MART) with ICS-formoterol has offered improved outcomes by simplifying regimens and reducing reliance on short-acting beta-agonists (SABA). However, evidence supporting MART and ICS-SABA regimens in younger children is limited, highlighting gaps in pediatric-focused research. Biologics targeting inflammatory pathways, such as omalizumab, mepolizumab, and dupilumab, represent a personalized approach for severe asthma but face challenges including high costs, limited long-term safety data, and uncertainty regarding their ability to modify disease progression. In addition, the complexity of treatment decisions is compounded by insufficient biomarkers and age-specific evidence to guide therapy. Addressing these gaps requires robust clinical studies and improved adherence strategies tailored to pediatric populations. This review critically examines current pharmacological strategies, unresolved issues, and evolving approaches in asthma management, emphasizing the need for personalized and evidence-based care. Enhancing treatment outcomes for pediatric asthma necessitates balancing therapeutic benefits with minimal adverse effects and leveraging ongoing research to inform future practice.

Background and objective: Globally, primary headache disorders, including migraine, tension type headache and cluster headache, are a leading cause of disability in children and adolescents. However, there has been a paucity of large-scale population-based studies to inform clinical decision making for paediatric patients. Consequently, we undertook a nationwide study to ascertain the current status of primary headache treatment in children and adolescents in China.

Methods: The study was based on the Hospital Prescription Analysis Cooperative Project of China, in which prescription data were extracted from a database of adolescent and child patients with a primary headache disorder from 160 hospitals in nine major Chinese cities from 2019 to 2023. In this study, we first analysed the trends in children and adolescents with primary headache in China over the past 5 years, stratified by age and sex, and analysed the trends in prescribing patterns. We then explored the differences in prescribing patterns among different populations and patients with different types of diagnoses, with the aim of analysing the current status of treatment for children and adolescents with primary headache in Chinese healthcare institutions in a multi-dimensional approach.

Results: A total of 1735 outpatients were included. The majority of patients were 15-17 years of age (65.0% in 2023). Migraine (66.1%) and tension-type headache (33.5%) were the predominant headache types. Calcium channel blockers, vitamins, antidepressants, analgesics and anticonvulsants were the most commonly prescribed classes of drugs. Flunarizine was the most widely prescribed drug, with a 5-year average proportion of 23.6%. The majority of drugs prescribed to children were vitamins (30.9%) and calcium channel blockers (28.7%). Differences in prescribing between patients with migraine and patients with tension-type headache were evident, with patients with migraine using predominantly calcium channel blockers (35.9%) and analgesics (20.8%), whereas patients with tension-type headache had a predominance of antidepressants (28.9%) and muscle relaxants (19.2%).

Conclusions: The prevalence of primary headaches progressively increased with age in children and adolescents. Migraine and tension-type headache were the predominant headache diagnoses at this stage. Flunarizine was the most prescribed drug for both children and adolescents, typically indicated for the preventive treatment of migraine, whereas antidepressants were the most commonly prescribed drug for the preventive treatment of tension-type headache. The majority of treatments were aligned with the available evidence and guideline recommendations. Nevertheless, there is still a paucity of evidence regarding the use of some drugs; these require further attention and clarification.