Pediatric Drugs最新文献

Medulloblastoma, the most common malignant brain tumor of childhood, is an aggressive embryonal tumor that arises from the posterior fossa. On the molecular level, four clinically relevant subgroups have been established, which have already been integrated into routine diagnostic procedures and treatment stratification. The initial step in treating medulloblastoma typically involves maximal safe surgical resection, followed by craniospinal irradiation in most patients (except very young children) and chemotherapy. Efforts to improve cure rates and reduce long-term detrimental effects led to the reduction in radiotherapy and adaptation of chemotherapy. Gradually, over the past decades, these strategies have resulted in significant improvements in treatment outcomes. However, patients with a medulloblastoma recurrence still fare badly, especially those children who already had radiotherapy as part of their initial treatment. Whereas there is no universal treatment strategy at relapse and the outcome remains poor, recently, the administration of anti-angiogenic metronomic therapy led to sustained long-term survival in a quarter of patients. Nonetheless, there remains an unmet need to improve survival and mitigate therapy-induced morbidity by developing new treatment strategies. Promising new approaches include targeting the Sonic Hedgehog pathway, addressing transcriptional and epigenetic drivers, improving drug delivery, and overcoming treatment resistance. Although the most common malignant brain tumor of childhood, the number of novel approaches in addition to a molecularly subdivided entity renders it difficult to form large clinical trials.

Background and objective: Evidence and clinical guidelines on methylphenidate dosing in different weight status groups are limited. This study aimed to evaluate real-world methylphenidate dosing practices and treatment discontinuation rates in children and adolescents in relation to weight status.

Method: We used data from the BMI Epidemiology Study Gothenburg cohort, which includes weight and height measurements linked to national registers. Exposures included body weight, standardised body mass index (zBMI), and body mass index (BMI) status. The main outcome was the dose and weight-adjusted dose of methylphenidate for the baseline and follow-up prescriptions. We used a logistic regression model to evaluate treatment discontinuation in relation to weight status, sex, and age.

Results: The study included 1741 children and adolescents who initiated methylphenidate treatment and had BMI available. Among them, 612 had a follow-up prescription with BMI available. Children and adolescents with overweight and obesity received slightly higher absolute doses of methylphenidate at baseline prescriptions, but lower weight-adjusted doses. Children and adolescents with underweight received higher weight-adjusted doses. Absolute dose increases between treatment initiation and follow-up were highest in children and adolescents with obesity and lowest in children and adolescents with underweight. Girls received higher absolute and weight-adjusted doses than boys at follow-up, while children over 12 years of age received higher absolute but lower weight-adjusted doses than children under 12 years. A significantly higher proportion of children and adolescents with baseline underweight discontinued treatment during the first year, compared with the normal weight group. Beside lower baseline zBMI, female sex and higher age were also significantly associated with treatment discontinuation during the first year.

Conclusion: Our findings suggest that weight status, sex, and age are significantly associated with differential methylphenidate dosing and treatment discontinuation in children and adolescents.

For adolescents and young adults (AYA) with any health condition, it is important that they learn to manage their condition and healthcare as they transition into adulthood. For AYA with childhood-onset long-term conditions, this is also fundamental for a successful transition from child- to adult-centred services, as this period is associated with a decline in important health behaviours, such as medication adherence, which in turn are associated with poorer clinical outcomes and increased mortality. Current evidence suggests that, even though AYA are at higher risk for non-adherence than other age groups, existing interventions are less likely to be effective, or may bring about more modest benefits, for AYA compared with younger children and older adults. There is still a need for novel, innovative approaches to medication adherence that can help better meet the unique needs of AYA groups. We suggest that developmentally informed and developmentally tailored approaches may offer a promising avenue to achieve this. The most widely reported AYA adherence issues are deeply intertwined with the different stages of AYA biopsychosocial development and, therefore, AYA development can be understood as a common thread underlying AYA adherence issues. Ensuring that AYA adherence-promoting interventions are relative to an ongoing developmental assessment is crucial, not only to better meet AYA needs as they gradually prepare for their transfer to adult care, but also to continue to do so in the often forgotten third phase of transitional care (i.e. following transfer) well into their late adolescence and young adulthood.

Background: Anti-interleukin-1 (IL-1) biologic disease-modifying anti-rheumatic drugs are the mainstay for several childhood rheumatic and autoinflammatory diseases. Long-term medication safety is a key consideration for chronic disease management.

Aim: The objective was to synthesise evidence on the long-term safety of anti-IL-1 medications in children and young people with rheumatic diseases, including autoinflammatory diseases.

Methods: The study protocol was registered prospectively (PROSPERO CRD420251000272). Original full text studies of at least ten patients presenting safety data on anti-IL-1 medications in children with rheumatic diseases were eligible for inclusion. Medline, Embase and Web of Science were searched from inception to 27 February 2025. The methodological index for non-randomized studies (MINORS) tool was used to assess risk of bias. All relevant safety outcomes were presented and synthesised. Meta-analysis was not performed owing to study heterogeneity.

Results: A total of 1660 unique records were screened, and 57 unique studies (3690 patients) were included. In total, 31 were retrospective cohort studies, and 10 were prospective interventional trials. Most studies were of moderate (n = 31) or high (n = 25) risk of bias. Rates of adverse events varied significantly between studies. Injection site reactions (particularly with anakinra) and minor infections were common. Infections were the most common type of serious adverse event. Drug reaction with eosinophilia and systemic symptoms (n = 3) and interstitial lung disease (including related conditions) (n = 9) were reported in patients with systemic onset juvenile arthritis only. Deaths (n = 16) and malignancies (n = 7) were uncommon, often occurring long after anti-IL-1 medication discontinuation and were often deemed to be unrelated to the anti-IL-1 medication.

Conclusions: Our results are consistent with the known safety profile of anti-IL-1 medications and show that they are generally safe for use in the context of childhood rheumatic and autoinflammatory diseases. This review of clinical trial and real-world data will help inform clinical decision-making and family counselling when initiating anti-IL-1 medications in children.

Growth hormone (GH) has been used to treat severe GH deficiency for more than 60 years, with other indications dependent upon approval from national medical societies and governmental agencies. Many changes in GH preparations have been made to improve safety, compliance, and efficacy, from the extraction of GH from human pituitary glands to recombinant hormone technology and from the use of vials and syringes to the use of more advanced devices. Adherence to treatment has always been highlighted as a key point in the success of treatment; new depot preparations permitting weekly administration have advantages in this regard. This review summarizes the history of GH use and provides an analysis of the new weekly administration products.