Pediatric Drugs最新文献

In addition to harming the respiratory system, COVID-19 can affect multiple organs. Children may develop a specific complication of COVID-19 called multisystem inflammatory syndrome in children (MIS-C) which could influence the vascular system of children and cause multiple coagulopathies in the body. Information on the use of thromboprophylaxis in this condition was collected via the review of various articles. In general, different factors in immune system responses can trigger the initiation of thrombotic events. Studies have shown that starting anticoagulant prophylaxis, which contributes to decreased thrombotic events, is dependent on the patient's condition and D-dimer levels. However, further studies on pediatric populations are needed to establish the role of anticoagulants in children with this condition.

Background: Chronic hand eczema (CHE) significantly impacts quality of life. Published literature on pediatric CHE (P-CHE) in North America including knowledge on epidemiology and standard evaluation and management is limited.

Objective: Our objective was to assess diagnostic practices when evaluating patients with P-CHE in the US and Canada, produce data on therapeutic agent prescribing practices for the disorder, and lay the foundation for future studies.

Methods: We surveyed pediatric dermatologists to collect data on clinician and patient population demographics, diagnostic methods, therapeutic agent selection, among other statistics. From June 2021 to January 2022, a survey was distributed to members of the Pediatric Dermatology Research Alliance (PeDRA).

Results: Fifty PeDRA members responded stating that they would be interested in participating, and 21 surveys were completed. For patients with P-CHE, providers most often utilize the diagnoses of irritant contact dermatitis, allergic contact dermatitis, dyshidrotic hand eczema, and atopic dermatitis. Contact allergy patch testing and bacterial hand culture are the most used tests for workup. Nearly all utilize topical corticosteroids as first line therapy. Most responders report that they have treated fewer than six patients with systemic agents and prefer dupilumab as first-line systemic therapy.

Conclusions: This is the first characterization of P-CHE among pediatric dermatologists in the United States and Canada. This assessment may prove useful in designing further investigations including prospective studies of P-CHE epidemiology, morphology, nomenclature, and management.

Ewing sarcoma is a translocation-associated sarcoma mainly impacting adolescents and young adults. The classic translocation (EWSR1::FLI1) leads to a fusion oncoprotein that functions as an aberrant transcription factor. As such, the oncogenic driver of this disease has been difficult to target pharmacologically and, therefore, the systemic therapies used to treat patients with Ewing sarcoma have typically been non-selective cytotoxic chemotherapy agents. The current review highlights recent clinical trials from the last decade that provide the evidence base for contemporary drug therapy for patients with Ewing sarcoma, while also highlighting novel therapies under active clinical investigation in this disease. We review recent trials that have led to the establishment of interval-compressed chemotherapy as an international standard for patients with newly diagnosed localized disease. We further highlight recent trials that have shown a lack of demonstrable benefit from high-dose chemotherapy or IGF-1R inhibition for patients with newly diagnosed metastatic disease. Finally, we provide an overview of chemotherapy regimens and targeted therapies used in the management of patients with recurrent Ewing sarcoma.

Background: In the neonatal period, cardiac hypertrophy (CH) has been commonly associated with hyperinsulinemic pathologies, and the first case of CH in an extremely preterm infant treated with insulin infusion has recently been reported. To confirm this association, we report a case series of patients who developed CH after insulin therapy.

Methods: Infants with gestational age < 30 weeks and birth weight < 1500 g, born from November 2017 to June 2022, were studied if they developed hyperglycemia requiring treatment with insulin and had echocardiographic diagnosis of CH.

Results: We studied 10 extremely preterm infants (24.3 ± 1.4 weeks) who developed CH at a mean age of 124 ± 37 h of life, 98 ± 24 h after the initiation of insulin therapy. All surviving patients had resolution of CH at discharge, while three of four (75%) of the deceased patients had persistent CH.

Conclusions: Our case series supports the association between the development of CH and insulin therapy in extremely preterm infants and suggests further caution and the need for echocardiographic monitoring when treating these fragile patients with insulin.

Acute kidney injury (AKI) is a commonly encountered comorbidity in critically ill children. The coexistence of AKI disturbs drug pharmacokinetics and pharmacodynamics, leading to clinically significant consequences. This can complicate an already critical clinical scenario by causing potential underdosing or overdosing giving way to possible therapeutic failures and adverse reactions. Current available studies offer little guidance to help maneuver such complex dosing regimens and decision-making in pediatric patients as most of them are done on heterogeneous groups of adult populations. Though there are some studies on drug dosing during continuous renal replacement therapy (CRRT), their utility is in question because of the recent advances in CRRT technology. Our review aims to discuss the principles of pharmacokinetics pertinent for honing the existing practices of drug dosing in critically ill children with AKI, and the various complexities and intricate challenges involved. This in turn will provide a framework to help enable caretakers to tailor dosing regimens in complex clinical setups with further ease and precision.

Pediatric convulsive status epilepticus (cSE) is a neurologic emergency with potential for morbidity and mortality. Rapid treatment and escalation of therapies to achieve early seizure control is paramount in preventing complications and providing the best patient outcomes. Although guidelines recommend early treatment, cessation of out-of-hospital SE is undermined by treatment delay and inadequate dosing. Logistical challenges include prompt seizure recognition, first-line benzodiazepine (BZD) availability, comfort and expertise in administration of BZD, and timely arrival of emergency personnel. In-hospital, SE onset is additionally impacted by delays to first- and second-line treatment and availability of resources. This review presents an evidence-based, clinically oriented review of pediatric cSE, including its definitions and treatments. It provides evidence and rationale for timely treatment of first-line BZD treatment followed by prompt escalation to second-line antiseizure medication therapies for established SE. Treatment delays and barriers to care are discussed, with practical considerations for opportunities for areas of improvement in the initial treatment of cSE.

Pain has a multifaceted impact on individuals worldwide, affecting their physical functioning, emotional well-being, and quality of life. Children (age < 18 years) have a high prevalence of conditions associated with pain, such as toothache, headache, earache, sore throat, and respiratory tract infections, many of which may be accompanied by fever. Globally, the pharmacologic treatment of pain in pediatric patients is limited largely to nonopioid analgesics, and dosing must account for differences in age, weight, metabolism, and risk of adverse effects. This narrative review summarizes the findings of a literature search on the pediatric indications, dosing approaches, dosing guidelines, and pharmacokinetics of paracetamol and ibuprofen, which are common pain medications available globally for self-care use in children. The review also discusses the risks and benefits associated with these agents. The current roles of paracetamol and ibuprofen in the symptomatic management of coronavirus disease 2019 (COVID-19) infection and in the management of post-COVID-19 immunization symptoms in children are also discussed. Therefore, while a very large amount of data over several decades is available for paracetamol and ibuprofen, an urgent need exists for well-designed studies of these medications for the management of pain and fever in pediatric patients with COVID-19 to ensure optimal relief with minimal toxicity.

Background: The prescription of antidepressant drugs during pregnancy has been steadily increasing for several decades. Meta-analyses (MAs), which increase the statistical power and precision of results, have gained interest for assessing the safety of antidepressant drugs during pregnancy.

Objective: We aimed to provide a meta-review of MAs assessing the benefits and risks of antidepressant drug use during pregnancy.

Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search on PubMed and Web of Science databases was conducted on 25 October, 2021, on MAs assessing the association between antidepressant drug use during pregnancy and health outcomes for the pregnant women, embryo, fetus, newborn, and developing child. Study selection and data extraction were carried out independently and in duplicate by two authors. The methodological quality of included studies was evaluated with the AMSTAR-2 tool. Overlap among MAs was assessed by calculating the corrected covered area. Data were presented in a narrative synthesis, using four levels of evidence.

Results: Fifty-one MAs were included, all but one assessing risks. These provided evidence for a significant increase in the risks for major congenital malformations (selective serotonin reuptake inhibitors, paroxetine, fluoxetine, no evidence for sertraline; eight MAs), congenital heart defects (paroxetine, fluoxetine, sertraline; 11 MAs), preterm birth (eight MAs), neonatal adaptation symptoms (eight MAs), and persistent pulmonary hypertension of the newborn (three MAs). There was limited evidence (only one MA for each outcome) for a significant increase in the risks for postpartum hemorrhage, and with a high risk of bias, for stillbirth, impaired motor development, and intellectual disability. There was inconclusive evidence, i.e., discrepant results, for an increase in the risks for spontaneous abortion, small for gestational age and low birthweight, respiratory distress, convulsions, feeding problems, and for a subsequent risk for autism with an early antidepressant drug exposure. Finally, MAs provided no evidence for an increase in the risks for gestational hypertension, preeclampsia, and for a subsequent risk for attention-deficit/hyperactivity disorder. Only one MA assessed benefits, providing limited evidence for preventing relapse in severe or recurrent depression. Effect sizes were small, except for neonatal symptoms (small to large). Results were based on MAs in which overall methodological quality was low (AMSTAR-2 score = 54.8% ± 12.9%, [19-81%]), with a high risk of bias, notably indication bias. The corrected covered area was 3.27%, which corresponds to a slight overlap.

Conclusions: This meta-review has implications for clinical practice and future research. First, these results suggest that antidepressant drug

Background: Nasal glucagon (NG) 3 mg is approved in Japan to treat hypoglycemia in pediatric patients with diabetes, but an NG clinical study has not been performed in Japanese children because of practical and ethical concerns.

Objective: The aim of this study is to support the dose rationale for NG 3 mg in Japanese pediatric patients with diabetes using modeling and simulation.

Methods: We used a pharmacokinetic/pharmacodynamic bridging approach to extrapolate the available clinical data to Japanese pediatric patients. Population pharmacokinetic/pharmacodynamic modeling was performed using data from seven clinical studies, including five studies in non-Japanese adults, one study in Japanese adults, and one study in non-Japanese pediatric patients. Simulation was then used to estimate glucagon exposure and glucose response after NG 3-mg administration for three age categories of Japanese pediatric patients: 4 to < 8, 8 to < 12, and 12 to < 18 years. Treatment success was defined as an increase in blood glucose to ≥ 70 or ≥ 20 mg/dL from nadir within 30 min after administration of NG 3 mg. Safety was assessed in relation to the predicted maximum glucagon concentration of NG 3 mg using NG clinical trial data and published data on intravenous and intramuscular glucagon.

Results: The data showed a rapid and robust glucose response following NG 3 mg in Japanese and non-Japanese adults and non-Japanese pediatric patients, with some differences in glucagon exposure observed across studies. The pharmacokinetic/pharmacodynamic model described the observed clinical data well, and simulations indicated that > 99% of hypoglycemic Japanese pediatric patients in all three age groups would achieve treatment success. Predicted glucose responses to NG 3 mg in Japanese pediatric patients were comparable to those of intramuscular glucagon. Maximum concentration was not associated with the occurrence and severity of common adverse events (nausea, vomiting, and headache) in NG clinical studies. Furthermore, the predicted maximum concentration in Japanese pediatric patients, despite being higher than the observed maximum concentration in NG clinical studies, was substantially lower than the observed maximum concentration of 1 mg of intravenous glucagon, without serious safety issues.

Conclusions: This analysis suggests NG 3 mg has robust efficacy without serious safety concerns in Japanese pediatric patients with diabetes.

The majority of pediatric human immunodeficiency virus (HIV) infections are the result of vertical transmissions that occur during pregnancy, childbirth, and breastfeeding. The treatment of all pregnant persons living with HIV remains a global health initiative. Early and consistent use of antiretroviral therapy throughout pregnancy and childbirth drastically reduces the risk of perinatal transmission of HIV, resulting in fewer children living with the disease worldwide. Given that the maternal HIV viral load is the strongest predictor of perinatal transmission, suppressive antiretroviral treatment during pregnancy is the principal means to eliminate transmission of HIV from mother to child. With the use of combined antiretroviral therapy, typically with dual-nucleoside reverse transcriptase inhibitors plus an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, HIV-infected mothers can now achieve virologic suppression to undetectable levels and yield a perinatal transmission rate of less than 2%. Important considerations of HIV treatment in pregnancy include the safety and efficacy of antiretroviral drugs, altered pregnancy-related pharmacokinetics, potential for birth defects or adverse neonatal outcomes, and individualized delivery planning based on maternal viral load. This practical review article summarizes the options, considerations, and recommendations for antiretroviral treatment in pregnancy to reduce perinatal HIV transmission and optimize health outcomes for mothers and infants worldwide.