Pediatric Drugs最新文献

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.

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.