Pediatric Drugs最新文献

Macitentan (Opsumit^®), an endothelin receptor antagonist (ERA) developed by Johnson & Johnson, is well established worldwide as monotherapy or combination therapy for the long-term treatment of pulmonary arterial hypertension (PAH). In September 2024, based on phase 3 clinical data in patients aged < 18 years, macitentan received its first pediatric approval in the EU as monotherapy or in combination for the long-term treatment of PAH in pediatric patients aged 2 years to < 18 years with WHO functional class (FC) II to III. Macitentan has also been approved in the UK for this indication. This article summarizes the milestones in the development of macitentan leading to the first pediatric approval for the long-term treatment of PAH.

Despite significant global reductions in cases of pneumonia during the last 3 decades, pneumonia remains the leading cause of post-neonatal mortality in children aged <5 years. Beyond the immediate disease burden it imposes, pneumonia contributes to long-term morbidity, including lung function deficits and bronchiectasis. Viruses are the most common cause of childhood pneumonia, but bacteria also play a crucial role. However, the optimal duration of antibiotic therapy for bacterial pneumonia remains uncertain in both low- and middle-income countries and in high-income countries. Knowing the optimal duration of antibiotic therapy for pneumonia is crucial for effective antimicrobial stewardship. This is especially important as concerns mount over rising antibiotic resistance in respiratory bacterial pathogens, which increases the risk of treatment failure. Numerous studies have focused on the duration of oral antibiotics and short-term outcomes, such as clinical cure and mortality. In contrast, only one study has examined both intravenous and oral antibiotics and their impact on long-term respiratory outcomes following pneumonia hospitalisation. However, study findings may be influenced by their inclusion criteria when children unlikely to have bacterial pneumonia are included. Efforts to differentiate between bacterial and non-bacterial pneumonia continue, but a validated, accurate, and simple point-of-care diagnostic test remains elusive. Without certainty that a child has bacterial pneumonia, determining the optimal duration of antibiotic treatment is challenging. This review examines the evidence for the recommended duration of antibiotics for treating uncomplicated pneumonia in otherwise healthy children and concludes that the question of duration is unresolved.

Meningococcal disease is rare but serious, often striking previously healthy adolescents or young adults, with substantial morbidity and mortality. The incidence of meningococcal disease in the USA declined even prior to the issuance of routine recommendations for vaccination, although an uptick in incidence has occurred since 2022. Routine recommendations for adolescent MenACWY vaccination were issued in 2005, and recommendations for adolescent MenB vaccination based on shared clinical decision-making (SCDM) were issued in 2015. Although meningococcal vaccines are safe and effective, their limited duration of protection coupled with low disease incidence result in a high cost per case averted by vaccination, most notably with MenB vaccines. The low cost-effectiveness raises ethical concerns about resource use and the role of economic analyses in policy decisions. However, the potential for substantial public health impact remains. Outer membrane vesicle (OMV)-containing MenB vaccines provide some protection against gonorrhea infections. The recent development of pentavalent ABCWY vaccines provide the opportunity to reduce the number of injections and simplify implementation, provided MenACWY and MenB vaccine schedules are harmonized. Vaccine attributes, implementation issues, and resource utilization will be important considerations in optimization of the US adolescent meningococcal vaccination strategy.

Neuroimaging, specifically magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and positron emission tomography (PET), plays an important role in improving the therapeutic landscape of pediatric neuropsychopharmacology by detecting target engagement, pathway modulation, and disease-related changes in the brain. This review provides a comprehensive update on the application of neuroimaging to detect neural effects of psychotropic medication in pediatrics. Additionally, we discuss opportunities and challenges for expanding the use of neuroimaging to advance pediatric neuropsychopharmacology. PubMed and Embase were searched for studies published between 2012 and 2024 reporting neural effects of attention deficit hyperactivity disorder (ADHD) medications (e.g., methylphenidate, amphetamine, atomoxetine, guanfacine), selective serotonin reuptake inhibitors (e.g., fluoxetine, escitalopram, sertraline), serotonin/norepinephrine reuptake inhibitors (e.g., duloxetine, venlafaxine), second-generation antipsychotics (e.g., aripiprazole, olanzapine, risperidone, quetiapine, ziprasidone), and others (e.g., lithium, carbamazepine, lamotrigine, ketamine, naltrexone) used to treat pediatric psychiatric conditions. Of the studies identified (N = 57 in 3314 pediatric participants), most (86%, total participants n = 3045) used MRI to detect functional pathway modulation or anatomical changes. Fewer studies (14%, total participants n = 269) used MRS to understand neurochemical modulation. No studies used PET. Studies that included healthy controls detected normalization of disease-altered pathways following treatment. Studies that focused on affected youth detected neuromodulation following single-dose and ongoing treatment. Neuroimaging is positioned to serve as a biomarker capable of demonstrating acute brain modulation, predicting clinical response, and monitoring disease, yet biomarker validation requires further work. Neuroimaging is also well suited to fill the notable knowledge gap of long-term neuromodulatory effects of psychotropic medications in the context of ongoing brain development in children and adolescents. Future studies can leverage advancements in neuroimaging technology, acquisition, and analysis to fill these gaps and accelerate the discovery of novel therapeutics, leading to more effective prescribing and ensuring faster recovery.

Youth under the age of 18 years represent a distinct subset of the population living with chronic kidney disease (CKD). The etiology of CKD differs greatly between children and adults, and young people with CKD face an extended lifetime living with their disease. Few rigorous randomized controlled trials in CKD have included people under the age of 18 years. As such, the recent success of CKD trials with sodium glucose co-transporter 2 inhibitors, mineralocorticoid antagonists, dual endothelin agonists, and hypoxia-induced factor prolyl hydroxylase inhibitors have largely not extended to children and adolescents. There are many reasons to believe these medications could prove as transformative in youth as they have in older adults, but trial data are missing. Innovative strategies are required to ensure that trials of recent, and future, agents in youth with CKD are successful.

Background: This study aimed to provide a comprehensive review of adverse events (AEs) associated with factor Xa (FXa) inhibitors in pediatric patients.

Methods: We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and the European Union Clinical Trials Register for English-language records from the establishment of the database up to October 17, 2023. Both randomized controlled trials and single-arm trials were included. AEs were analyzed using a Bayesian hierarchical model. For the pharmacovigilance study, data from the US Food and Drug Administration Adverse Event Reporting System from January 1, 2007, to December 31, 2023, were obtained. The proportional imbalance method and the Medicines and Healthcare products Regulatory Agency method were used to detect AE signals. Further characterization of patients presenting with AEs was performed.

Results: Of 451 records identified, 12 eligible studies were included. A total of 50.6% (95% Bayesian credible interval [CrI] 33.1-67.2, τ = 0.796) of patients experienced at least one AE, and 9.9% (95% CrI 3.9-19.5, τ = 0.552) developed at least one serious AE. Major and clinically relevant non-major bleeding occurred in 2.4% (95% CrI 0.8-4.8, τ = 1.61) of patients. The most common bleeding AEs were epistaxis (8.4% [95% CrI 3.9-14.9, τ = 1.96]), subcutaneous hematoma (6.4% [95% CrI 0.5-26.2, τ = 0.54]), and wound hemorrhage (3.7% [95% CrI 0.4-13.3, τ = 0.55]). Non-hemorrhagic AEs were pyrexia (9.2% [95% CrI 4.6-15.3, τ = 1.18]), vomiting (7.8% [95% CrI 4.0-12.3, τ = 0.08]), and abdominal pain (7.4% [95% CrI 1.5-19.4, τ = 0.84]). A total of 39 AE signals were detected in the pharmacovigilance study. The top three highest overall relative odds ratio (ROR) for AEs were observed for haemorrhoidal hemorrhage at 1211.82 (95% CI, 312.69-4696.29), thrombophlebitis at 134.64 (95% CI, 42.18-429.81), and deep vein thrombosis at 68.3 (95% CI, 42.53-109.68). Patients experiencing bleeding AEs had received a mean dosage of rivaroxaban 0.16 mg/kg and apixaban 0.08 mg/kg.

Conclusions: Systematically quantified AEs of FXa inhibitors in clinical trials and real-world studies provide an important guide for clinicians. The use of FXa inhibitors in pediatric patients is associated with an acceptable rate of AEs. The most common bleeding AE was epistaxis. Pediatric patients treated with FXa inhibitors were more prone to hemorrhoidal hemorrhage. A safe approach may involve prior use of other anticoagulants followed by careful administration of FXa inhibitors, with a dosing regimen tailored to age and weight. Close monitoring is recommended for peri-procedural anticoagulation and vomiting.

Background: The effectiveness of crisaborole for proactive treatment of atopic dermatitis (AD) is not well established.

Objectives: This study aims to investigate the efficacy and safety of a proactive treatment strategy with 2% crisaborole ointment for managing mild-to-moderate AD in children.

Patients and methods: In this 16-week randomized-controlled trial, children aged 2-17 years with mild-to-moderate AD were enrolled. All participants received treatment with 0.1% mometasone furoate cream for 2 weeks. Those with an IGA score of ≤ 1 were randomly assigned in a 1:1 ratio to either the proactive treatment group, which received crisaborole combined with emollient twice daily, or the reactive treatment group, which received emollients alone, and in the event of disease relapse, both groups received 0.1% mometasone furoate cream as rescue treatment.

Results: Of the 153 patients screened, 142 were randomized; 73 to the proactive treatment group and 69 to the reactive treatment group. At the end of the 16-week trial, the proactive treatment group had a relapse rate of 43.84%, significantly lower than the 71.01% relapse rate in the reactive group (P = 0.001). Additionally, the proactive treatment group demonstrated a significant reduction in the need for mometasone furoate prescriptions at weeks 4, 8, 12, and 16 (P < 0.05). Improvements were also observed in IGA, EASI, PP-NRS, and POEM scores at 12 weeks (P < 0.05). No significant differences in adverse events were found between the groups (χ² = 2.237, P = 0.135).

Conclusions: Proactive treatment with crisaborole ointment for children older than 2 years with mild-to-moderate AD effectively reduces flare-ups and reliance on topical corticosteroids, demonstrating good tolerability and safety.

Chinese clinical trial registry: ChiCTR2100054340 (Date of Trial Registration: 14 December 2021).

Background and objectives: Females of reproductive age are increasingly using attention deficit hyperactivity disorder (ADHD) medication, but its use during pregnancy and breastfeeding is largely unknown. The aim of this study is to examine the prevalence of ADHD medication fills during pregnancy and breastfeeding, including characteristics of these females and cohort differences over time.

Methods: We conducted a descriptive study using Danish nationwide registers. Within cohorts of pregnant and breastfeeding females, we calculated the prevalence of ADHD medication (methylphenidate, amphetamine, dexamfetamine, lisdexamfetamine, modafinil, atomoxetine, clonidine and guanfacine) fills and described sociodemographic and clinical characteristics across groups with fills, no fills and previous fills. Cohort differences in ADHD medication fills during pregnancy for 2005-2010, 2011-2016 and 2017-2022 were examined.

Results: In this cohort of 1,077,279 pregnancies, ADHD medication fills increased from 0.08 to 7.71 per 1000 individuals between 2005 and 2022. Among 446,485 breastfeeding females, fills increased from 0.55 to 3.67 per 1000 individuals from 2012 to 2022. Compared with the group with no fills, females filling ADHD medication during pregnancy and breastfeeding were younger, had lower levels of education, were more often smoking during pregnancy, utilised more psychiatric healthcare and had concurrent fills of other psychotropic medication. Cohort differences over time revealed that females filling ADHD medication during pregnancy in 2017-2022 were older, had higher levels of education, smoked less during pregnancy, had fewer psychiatric contacts and were less likely to fill other psychotropic medications compared with females in the earlier cohorts.

Conclusions: Results showed an increasing prevalence of ADHD medication fills during pregnancy and breastfeeding in Denmark over time, surpassing the increase observed generally in females of reproductive age filling ADHD medication. Results revealed a difference in characteristics of females filling ADHD medication during pregnancy over time, suggesting a shift in pregnancy treatment patterns.

Necrotizing enterocolitis (NEC) is a relatively rare but very severe gastrointestinal disease primarily affecting very preterm infants. NEC is characterized by excessive inflammation and ischemia in the intestines, and is associated with prolonged, severe visceral pain. Despite its recognition as a highly painful disease, current pain management for NEC is often inadequate, and research on optimal analgesic therapy for these patients is lacking. Insight into the mechanisms underlying intestinal pain in infants with NEC-visceral pain-could help identify the most effective analgesics for these vulnerable patients. Therefore, this comprehensive review aims to provide an overview of visceral nociception, including transduction, transmission, modulation, and experience, and discuss the implications for analgesic therapy in preterm infants with NEC. The transmission of visceral pain differs from that of somatic pain, contributing to the diffuse nature of visceral pain. Studies evaluating the effectiveness of analgesics for treating visceral pain in infants are scarce. However, research in visceral pain models highlights agents that may be particularly effective for treating visceral pain based on their mechanisms of action. Further research is necessary to determine whether agents that have shown promise for treating visceral pain in preclinical studies and adults are effective in infants with NEC as well.