Pediatric Drugs最新文献

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.

Fungal infections in neonates are potentially life threatening. The differential diagnosis for neonatal rashes is extensive, with common culprits including both bacteria and fungi. Candida albicans is the predominant fungal pathogen, causing infections that range from superficial disease to severe systemic conditions, including sepsis and meningitis. Neonates, especially those who are preterm, are particularly susceptible because of developmentally immature immune systems and the use of invasive procedures and devices in neonatal intensive care units. Congenital cutaneous candidiasis, acquired in utero or during delivery, can lead to disseminated infection with high mortality rates. Early diagnosis and prompt antifungal treatment are crucial but challenging because of subtle clinical presentations, making accurate identification of the offending organism essential for selecting the appropriate treatment. Candida species account for the majority of neonatal fungal infections, with different species necessitating distinct treatments because of varying susceptibility profiles. Aspergillus, another significant pathogen, poses high mortality risks and can present either cutaneously or systemically. Malassezia, though less common, primarily affects preterm infants with catheter-related fungemia. Other fungal species, including Zygomycetes, Trichosporon, and Cryptococcus, rarely produce neonatal infections but are noteworthy for consideration. Treatment of fungal infection is critical despite the relative paucity of information regarding the clinical pharmacology of many antifungal drugs in neonates. We review the major antifungal agents (e.g., amphotericin B, the echinocandins, the azoles) and provide pharmacologic and dosing information. Finally, preventive strategies, including the use of stringent aseptic techniques and careful clinical monitoring, are essential to mitigate both the incidence and severity of these infections in neonates and infants in the first months of life.

Background: Anakinra is an interleukin-1 receptor antagonist (IL-1Ra). Since IL-1 has been shown to play a key role in the etiology of different autoinflammatory diseases, blocking its pathway has become an important therapeutic target, even in neonates.

Aims: We aimed to report our experience in using anakinra to treat specific neonatal inflammatory conditions.

Methods: We described the clinical management with anakinra of five cases of neonates or infants up to 3 months of age admitted to the neonatal intensive care unit (NICU) of Bambino Gesù Children's Hospital IRCCS in Rome (Italy) from 2020 onwards. Medical history and clinical data concerning NICU hospitalization were collected from the electronic medical records. Furthermore, we performed a literature review of off-label anakinra in the first 3 months of life, up to 5 April 2024. We excluded from this review cases of cryopyrin-associated periodic syndrome, deficiency of the interleukin-1 receptor antagonist, and mevalonate kinase deficiency, for which anakinra is a known treatment.

Results: We reported three off-label cardiorespiratory reasons to use IL-1Ra from our series: (i) chronic lung disease with pulmonary hypertension, (ii) interstitial lung disease with pulmonary hypertension to facilitate the weaning from respiratory support, and (iii) post-surgical polyserositis if effusions accumulate despite drainage. In all our patients, the drug was administered at a dosage of 10 mg/kg/day. The route of administration was chosen based on the patient's clinical characteristics, with the subcutaneous and intravenous routes being comparable in efficacy. The duration of therapy was modulated based on the patient's clinical response, with a minimum duration of 4 months. A total of 308 retrieved articles were screened, and then full texts of records deemed eligible for inclusion were assessed. Based on the literature search and our five cases, a total of 17 infants were treated with anakinra outside its approved indications. The major off-label use was for hemophagocytic lymphohistiocytosis/macrophage activation syndrome, followed by multisystem inflammatory syndrome in children and Kawasaki disease, as in two of our cases.

Conclusions: According to the results of our case series and review of the literature, the off-label use of anakinra in neonates with inflammatory conditions refractory to first-line therapy could be considered. Prospective, multicenter research is necessary to determine whether anakinra is a safe treatment option for these infants to prevent early inflammatory illnesses and in which situations it could enhance clinical results.

Prader-Willi syndrome is a rare neurodevelopmental disorder that impacts the musculoskeletal, endocrine, pulmonary, neurologic, ocular, and gastrointestinal systems. In addition, individuals with Prader-Willi syndrome have issues with cognitive development, characteristic behavioral problems, and perhaps most profoundly, appetite control. Currently, the only US Food and Drug Administration-approved therapy for Prader-Willi syndrome is growth hormone, which has been Food and Drug Administration approved for > 20 years for the treatment of growth failure in Prader-Willi syndrome. Growth hormone has shown to improve many aspects of this syndrome, including final height, body composition, developmental milestones, and cognition, but it does not affect hyperphagia, which is the hallmark symptom of this condition. Over the past 15 years, there have been several medication trials for the treatment of hyperphagia in Prader-Willi syndrome, but thus far, all have failed to achieve Food and Drug Administration approval for a variety of reasons. However, hyperphagia is the most life-limiting symptom of Prader-Willi syndrome, thus new pharmacologic therapies are desperately needed. We review ongoing and recently completed clinical trials for hyperphagia. Other issues in Prader-Willi syndrome that significantly impact quality of life include excessive daytime sleepiness and severe behavioral problems. We examine the medication trials to address these issues.

The aryl hydrocarbon receptor (AhR) has an integral role in maintaining skin homeostasis. Tapinarof cream 1% (VTAMA^®) is an AhR agonist developed by Dermavant Sciences, an Organon Company, as a once-daily topical treatment for plaque psoriasis and atopic dermatitis (AD). It was first approved in May 2022 in the USA for the topical treatment of plaque psoriasis in adults. It was then approved in June 2024 in Japan for the topical treatment of plaque psoriasis in adults and AD in adults and pediatric patients 12 years of age and older. In December 2024, it was approved in the USA for the topical treatment of AD in adults and pediatric patients 2 years of age and older. This article summarizes the milestones in the development of tapinarof cream 1% leading to this first pediatric approval.