Pediatric Drugs最新文献

Background: Baclofen can decrease rumination frequency in adults with rumination syndrome. Outcomes of baclofen treatment in children with rumination syndrome have not been described. The aim of this study was to examine the safety and efficacy of baclofen in children with rumination syndrome in combination with behavioral therapy at a single center.

Methods: We performed a retrospective review of children aged 0-18 years with rumination syndrome based on Rome criteria and prescribed baclofen by a pediatric gastroenterologist at the Nationwide Children's Hospital, Columbus, Ohio, USA, between 2012 and 2019. Children without follow-up data or who were prescribed baclofen for other symptoms were excluded.

Results: We identified 44 children with rumination syndrome who were prescribed baclofen by a pediatric gastroenterologist. Seventeen either did not have follow-up data or never started the medication. We included 27 patients in the study: 22 (81.5%) female, median age 14.5 years (range 10-18 years) and 100% Caucasian. Twenty patients (74%) received baclofen 5 mg and seven patients (26%) received baclofen 10 mg three times daily. Most patients received behavioral therapy and baclofen simultaneously. Thirteen patients (48%) reported improvement in symptoms, primarily a decrease in rumination frequency, at their first follow-up visit. Regurgitation frequency per week decreased after starting baclofen (p < 0.05). One patient experienced dizziness. No other side effects were reported.

Conclusion: Nearly half of our patients with rumination syndrome improved after baclofen. It was well tolerated with minimal side effects. This suggests that baclofen in addition to behavioral therapy can improve symptoms of rumination syndrome. Prospective, controlled studies in a larger cohort of children with rumination syndrome are needed to confirm these findings.

Functional constipation is a common problem in childhood worldwide and has a great impact on social, physical, and emotional functioning of affected children and their caregivers. It is a clinical diagnosis based on the Rome IV criteria. Non-pharmacological treatment involves education, demystification, lifestyle advice, and toilet training. Pharmacological treatment consists of disimpaction, maintenance treatment, and eventually weaning if possible. Polyethylene glycol is considered as the first choice of laxative for both disimpaction and maintenance treatment. Different osmotic laxatives, stimulant laxatives, lubricants, and enemas are available as alternative pharmacological treatment options. Novel drugs are emerging but evidence to support the widespread application of these drugs in the pediatric population is often lacking and more high-quality research is needed in this field. If children remain symptomatic despite optimal pharmacological treatment, botulinum toxin injections in the anal sphincter can be considered as an alternative, more invasive treatment option. This review provides an update on currently available literature concerning the pharmacologic treatment of functional constipation in children.

As the activity of certain drug metabolizing enzymes or transporter proteins can vary with age, the effect of ontogenetic and genetic variation on the activity of these enzymes is critical for the accurate prediction of treatment outcomes and toxicity in children. This makes pharmacogenetic research in pediatrics particularly important and urgently needed, but also challenging. This review summarizes pharmacogenetic studies on the effects of genetic polymorphisms on pharmacokinetic parameters and clinical outcomes in pediatric populations for certain drugs, which are commonly prescribed by clinicians across multiple therapeutic areas in a general hospital, organized from those with the most to the least pediatric evidence among each drug category. We also further discuss the research status of the gene-guided dosing regimens and clinical implementation of pediatric pharmacogenetics. More and more drug-gene interactions are demonstrated to have clinical validity for children, and pharmacogenomics in pediatrics have shown evidence-based benefits to enhance the efficacy and precision of existing drug dosing regimens in several therapeutic areas. However, the most important limitation to the implementation is the lack of high-quality, rigorous pediatric prospective clinical studies, so adequately powered interventional clinical trials that support incorporation of pharmacogenetics into the care of children are still needed.

Obesity-related asthma is associated with a high disease burden and a poor response to existent asthma therapies, suggesting that it is a distinct asthma phenotype. The proposed mechanisms that contribute to obesity-related asthma include the effects of the mechanical load of obesity, adipokine perturbations, and immune dysregulation. Each of these influences airway smooth muscle function. Mechanical fat load alters airway smooth muscle stretch affecting airway wall geometry, airway smooth muscle contractility, and agonist delivery; weight loss strategies, including medically induced weight loss, counter these effects. Among the metabolic disturbances, insulin resistance and free fatty acid receptor activation influence distinct signaling pathways in the airway smooth muscle downstream of both the M2 muscarinic receptor and the β₂ adrenergic receptor, such as phospholipase C and the extracellular signal-regulated kinase signaling cascade. Medications that decrease insulin resistance and dyslipidemia are associated with a lower asthma disease burden. Leptin resistance is best understood to modulate muscarinic receptors via the neural pathways but there are no specific therapies for leptin resistance. From the immune perspective, monocytes and T helper cells are involved in systemic pro-inflammatory profiles driven by obesity, notably associated with elevated levels of interleukin-6. Clinical trials on tocilizumab, an anti-interleukin antibody, are ongoing for obesity-related asthma. This armamentarium of therapies is distinct from standard asthma medications, and once investigated for its efficacy and safety among children, will serve as a novel therapeutic intervention for pediatric obesity-related asthma. Irrespective of the directionality of the association between asthma and obesity, airway-specific mechanistic studies are needed to identify additional novel therapeutic targets for obesity-related asthma.

Background and objective: Amikacin is preferred in treating Gram-negative infections in neonates and it has a narrow therapeutic window. The population pharmacokinetic modeling approach can aid in designing optimal dosage regimens for amikacin in neonates. In this study, we attempted to identify the suitable population pharmacokinetic model from the published reports for the study population from an Indian setting.

Methods: Published population pharmacokinetic studies for amikacin in neonates were identified. Data on structural models and typical pharmacokinetic parameters were extracted from the studies. For the clinical study, neonates who met the inclusion criteria were enrolled in the study from the NICU, Kasturba Medical College, Manipal, during Jan 2020 to March 2022. Drug concentrations were estimated, and demographic and clinical data were collected. Identified population pharmacokinetic models were used to predict the amikacin concentrations in neonates. Predicted concentrations were compared against the observed concentrations. Differences between predicted and observed concentrations were quantified using statistical measures. The population pharmacokinetic model, which was able to predict the data well, is considered a suitable model for the study population. Dosing regimens were suggested for neonates using the pharmacometric simulation approach generated by the selected model.

Results: A total of 43 plasma samples were collected from 31 neonates. Twelve population pharmacokinetic models were found for amikacin in neonates. The predictive performance of the 12 studies was performed using clinical data. A two-compartment model reported by Illamola et al. predicted the amikacin concentrations better than other models. Illamola et al. reported creatinine clearance and body weight as the significant covariates impacting the pharmacokinetic parameters of amikacin. This model was able to predict the clinical data with 29.97% and 0.686 of relative median absolute prediction error and relative root mean square error, respectively, which is the best among the published models. The Illamola et al. model was selected as the final model to perform pharmacometric simulations for the subjects with different combinations of creatinine clearance and body weight. Dosage regimens were designed to attain target therapeutic concentrations for the virtual subjects and a nomogram was developed.

Conclusions: The population pharmacokinetic model reported by the Illamola et al. model was selected as the final model to explain the clinical data with the lowest relative median absolute prediction error and relative root mean square error when compared with other models. An amikacin nomogram was developed for the neonates whose creatinine clearance and body weight ranged between 10 and 90 mL/min and between 2 and 4 kg, respectively. A developed nomogram can assist clinician

Sodium thiosulfate (Pedmark^®) is a chemoprotectant/antioxidant developed by Fennec Pharmaceuticals (formerly Adherex Technologies) to reduce to risk of hearing loss associated with cisplatin. Sodium thiosulfate reduces the risk of ototoxicity by interacting directly with cisplatin to produce inactive platinum species, as well as by causing intracellular effects (such as increasing antioxidant glutathione levels and inhibition of oxidative stress) after entering the cells through the sodium sulfate cotransporter 2. In September 2022, sodium thiosulfate received its first approval in the USA for reducing the risk of ototoxicity associated with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumours. Sodium thiosulfate is under regulatory review in the EU for the prevention of ototoxicity induced by cisplatin chemotherapy in patients 1 month to < 18 years of age with localised, non-metastatic, solid tumours. This article summarizes the milestones in the development of sodium thiosulfate leading to this pediatric first approval for reducing the risk of ototoxicity associated with cisplatin in pediatric patients.

Background: Plexiform neurofibromas are benign neoplasms that develop in 20-50% children with neurofibromatosis type 1 (NF1). Selumetinib was approved as treatment for symptomatic and inoperable plexiform neurofibromas. Subclinical left ventricular ejection fraction reduction is a less common effect of selumetinib.

Objective: We aimed to investigate the contractile function of the heart in a cohort of children with NF1 treated with selumetinib.

Methods: We designed a cross-sectional study including 17 patients with NF1 who received selumetinib. Echocardiographic parameters were compared with a cohort of 17 healthy children matched by sex and age and another group of 17 children with untreated NF1.

Results: Compared with healthy controls, patients with NF1 treated with selumetinib had lower mean values of global longitudinal strain (- 22.9 ± 2% vs -25.5 ± 2%; p = 0.001), fractional shortening (36 ± 4% vs 43 ± 8%; p = 0.02) and tricuspid annular plane systolic excursion (19 ± 3 mm vs 23 ± 2 mm; p = 0.001); no difference was found in left ventricular ejection fraction (63 ± 4% vs 65 ± 3%; p = 0.2 respectively). Median treatment time with selumetinib at the time of the echocardiographic evaluation was 22 ± 16 months.

Conclusions: Patients with NF1 treated with selumetinib may experience subtle changes in systolic function identified by global longitudinal strain and not revealed by left ventricular ejection fraction. Global longitudinal strain might be useful to monitor cardiac function in this cohort of patients for the duration of therapy.

Background: Long-acting injectable antipsychotics (LAIAs) are an efficacious and well-tolerated treatment in adults with schizophrenia spectrum disorders (SSD). However, there is less evidence for their use in children and adolescents.

Objectives: The aim of this systematic review was to summarize findings regarding the effectiveness and side effects of LAIA in children and adolescents with SSD.

Methods: Four databases (Web of Science, PubMed, MEDES, and Dialnet) were systematically searched for articles published between inception and 12 March, 2022, with the following inclusion criteria: (1) original articles or case reports; (2) providing data on efficacy/effectiveness or safety/tolerability of LAIA treatment in children and adolescents diagnosed with SSD (schizophrenia, schizoaffective disorder, schizophreniform disorder, non-affective psychotic disorder); (3) mean age of samples ≤ 18 years; and (4) written in English or Spanish. Exclusion criteria were review articles, clinical guides, expert consensus as well as posters or oral communication in conferences. The risk of bias was assessed using the ROBIS tool.

Results: From 847 articles found, 13 met the inclusion criteria. These included seven single case reports or case series, four retrospective chart reviews, a 24-week open-label trial, and one observational prospective study, covering a total of 119 adolescents (aged 12-17 years) with SSD. Almost all the articles described data on second-generation LAIA (53 patients on risperidone [once every other week], 33 on paliperidone palmitate [once monthly], 10 on aripiprazole [once monthly], and two on olanzapine pamoate [once monthly]). Twenty-one patients were reported to be only on first-generation LAIAs. Non-adherence was the main reason for starting an LAIA. In all of the studies, the use of LAIAs was associated with improvement in the patients' symptoms.

Conclusions: There are few studies assessing the use of LAIAs in adolescents with SSD. Overall, these treatments have suggested good effectiveness and acceptable safety and tolerability. However, we found no studies examining their use in children aged < 12 years. The problems and benefits linked to this type of antipsychotic formulation in the child and adolescent population require further study, ideally with prospective, controlled designs.

Objectives: We evaluated the characteristics and sought risk factors for hospitalization in children who return to the emergency department within 7 days of discharge after oral or intravenous ondansetron treatment for vomiting. The secondary aim was to determine whether the diagnosis of any serious condition had been delayed as the result of discharge after ondansetron treatment.

Methods: This retrospective analysis of the medical records of children who had been treated for vomiting with ondansetron in a tertiary care pediatric emergency department and revisited the emergency department within 7 days was performed between 2017 and 2019. We compared demographic and clinical features as well as management between hospitalized and discharged patients, focusing upon potentially delayed diagnoses of serious conditions.

Results: Fifty of the 89 ondansetron-treated children (56.2%) who revisited the emergency department were discharged home after their second emergency department visit and the remaining 39 (43.8%) were hospitalized. No parameter of the management of the first visit was predictive of the outcome of the revisit. Five revisit patients (5.6%) were newly diagnosed with a serious condition, with intussusception and ovarian torsion being the most substantial time-sensitive delays (the other diagnoses were pneumonia and aseptic meningitis).

Conclusions: Physicians assessing patients who had been treated with ondansetron as supportive care for vomiting at an earlier visit to the pediatric emergency department should consider alternative diagnoses despite initial clinical improvement. No definitive risk factor for readmission was identified, but a high level of alertness to a possible meningeal or acute abdominal source is imperative.