Journal of Pediatric Pharmacology and Therapeutics最新文献

The aim of this review is to present the information a clinician will need when considering alpelisib therapy for a patient diagnosed with PIK3CA-related overgrowth spectrum (PROS). PROS is a condition caused by a somatic recessive gain-of-function mutation in the gene encoding phosphatidylinositol-3-kinase (PI3K). PROS is rare, affecting approximately 14 births per 1 million. PROS affects many different tissues including skin, bone, vascular, adipose, and connective tissues, thus its presentations vary widely. The presentation of PROS is often described as mosaic, as the disease typically does not affect all cells in the body. For patients two years of age and older requiring systemic therapy, alpelisib is an option which was recently granted accelerated approval by the US Food and Drug Administration (FDA) on April 5, 2022. Alpelisib is an inhibitor of PI3K, slowing the progression of existing lesions and preventing new lesions in patients with PROS. Important drug interactions exist with both CYP3A4 inducers and CYP2C9 substrates. Additionally, providers of patients receiving alpelisib should be aware of potential side effects including hypersensitivity, severe cutaneous adverse reactions, hyperglycemia, pneumonitis, diarrhea, and embryo-fetal toxicity. Despite the potential for adverse events, alpelisib has provided clinical benefit to many patients with PROS as evidenced by the current literature. This review collects and summarizes the currently available evidence, including a recently published case series and multiple case reports. Alpelisib is a promising new option for patients with PROS.

Objective: To evaluate the physical intravenous Y-site compatibility of 29 combinations of medications at commonly used pediatric concentrations using both existing and novel techniques.

Methods: Medication combinations included were selected by a varied group of pediatric inpatient pharmacists, and then assessed by 3 independent reviewers for existing literature. For each combination, 2 different medications were mixed together in a 1:1 ratio and incubated at room temperature for 4 hours to simulate Y-site administration. Each sample was then analyzed using the US Pharmacopeia (USP) <788> recommended analytical technique of light obscuration (LO) in addition to novel flow imaging (FI) microscopy and backgrounded membrane imaging (BMI). Physical compatibility was determined using USP chapter <788> large volume particle count limits for all techniques.

Results: A total of 29 different medication combinations were studied. Five combinations met criteria for compatibility by all 3 techniques. The remaining 24 combinations reached the threshold to be considered incompatible by at least 1 of the 3 techniques. Light obscuration, BMI, and FI identified 14%, 59%, and 76% of combinations as incompatible, respectively. All samples deemed incompatible by LO were also incompatible by at least 1 of the other 2 techniques. Flow imaging and BMI results agreed in 69% of samples tested.

Conclusions: Most combinations tested were found to be incompatible by at least 1 of the 3 instruments used. Light obscuration appears to have reduced accuracy for identifying particulate resulting in physical medication incompatibility when compared with the novel techniques of FI and BMI.

Objective: Critically ill pediatric patients commonly experience opioid-induced dysmotility. Methylnaltrexone, a subcutaneously administered, peripherally acting mu-opioid receptor antagonist, is a compelling adjunct to enteral laxatives in patients with opioid-induced dysmotility. Data for methylnaltrexone use in critically ill pediatric patients are limited. The purpose of this study was to determine the effectiveness and safety of methylnaltrexone for opioid-induced dysmotility in critically ill infants and children.

Methods: Patients younger than 18 years who received subcutaneous methylnaltrexone from January 1, 2013, through September 15, 2020, in the pediatric intensive care units at an academic institution were included in this retrospective analysis. Outcomes included incidence of bowel movement, enteral nutrition feeding volume, and adverse drug events.

Results: Twenty-four patients, median age 3.5 years (IQR, 0.58-11.1), received 72 methylnaltrexone doses. The median dose was 0.15 mg/kg (IQR, 0.15-0.15). Patients were receiving a mean ± SD of 7.5 ± 4.5 mg/kg/day of oral morphine milligram equivalents (MMEs) at methylnaltrexone administration and received opioids for median 13 days (IQR, 8.8-21) prior to methylnaltrexone administration. A bowel movement occurred within 4 hours following 43 (60%) administrations and within 24 hours following 58 (81%) administrations. Enteral nutrition volume increased by 81% (p = 0.002) following administration. Three patients had emesis and 2 received anti-nausea medication. No significant changes in sedation or pain scores were observed. Withdrawal scores and daily oral MMEs decreased following administration (p = 0.008 and p = 0.002, respectively).

Conclusions: Methylnaltrexone may be an effective treatment for opioid-induced dysmotility in critically ill pediatric patients with low risk of adverse effects.

Objective: Five commercially available amoxicillin-clavulanate (AMC) ratio formulations contribute to ratio selection variability with efficacy and toxicity implications. The objective of this survey was to determine AMC formulation use patterns across the United States.

Methods: A multicenter practitioner survey was distributed to multiple listservs (American College of Clinical Pharmacy pediatrics, infectious diseases, ambulatory care, pharmacy administration; American Society of Health-System Pharmacists; Pediatric Pharmacy Association members), and selected pediatric Vizient members in June 2019. Responses were screened for multiples within institutions. Repeated organization responses were identified (n = 37) and excluded if the duplicate matched another response from the same organization exactly (n = 0).

Results: One hundred ninety independent responses were received. Nearly 62% of respondents represented a children's hospital within an acute care hospital; remainder being from stand-alone children's hospitals. Around 55% of respondents indicated prescribers were responsible for choosing the patient-specific formulation for inpatients. Nearly 70% of respondents indicated multiple formulations were available due to clinical need (efficacy, toxicity, measurable volume), whereas over 40% responded that the number of liquid formulations were limited to decrease the potential for error. Variability was demonstrated among institutions using ≥ 2 different formulations for acute otitis media (AOM), sinusitis, lower respiratory tract infection, skin and soft tissue infection, and urinary tract infection (33.6%, 37.3%, 41.5%, 35.8%, and 35.8%, respectively). The 14:1 formulation was the most common, but not exclusive, for AOM, sinusitis, and lower respiratory tract infections with 2.1%, 2.1%, and 2.6% of respondents indicating use of the 2:1 formulation and 10.9%, 15%, and 16.6% of respondents indicating use of the 4:1 formulation.

Conclusions: Significant AMC formulation selection variability exists across the United States.

Objective: To evaluate the effect of a multidisciplinary practice bundle on the incidence of delirium in the pediatric intensive care unit (PICU).

Methods: This retrospective observational study evaluated patients admitted to the PICU with Cornell Assessment of Pediatric Delirium (CAPD) scoring. A multidisciplinary practice bundle was implemented involving pharmacists, nurses, and providers. Study endpoints included CAPD scores greater than or equal to 9, length of hospital stay, and days spent in the PICU.

Results: The study included 192 patients. The pre-intervention mean CAPD score was 3.59, maximum of 24 (range, 0-24), and 4.5% of patients had a score ≥9. The post-intervention mean score was 4.04, maximum of 21 (range, 0-21), and 9.6% of patients had a score ≥9. The pre-intervention mean total length of hospital stay was 8.7 days, maximum of 149 days (range, 0-149); the mean number of days spent in PICU was 4.5 days, and maximum days in PICU was 89 days (range, 0-89). The post-intervention mean total length of hospital stay was 8.8 days, maximum of 57 days (range, 0-57); the mean number of days spent in PICU was 3.9 days, and maximum days in PICU was 31 days (range, 0-31).

Conclusions: Implementation of a multidisciplinary practice bundle, the use of CAPD scores, and the stewardship of high-risk patients increased overall awareness of the occurrence of pediatric delirium in the PICU and reduced length of stay in the intensive care unit and therefore reduced cost for families and the institute.

Objectives: This study aimed to determine if there is a difference in health care use in pediatric asthma exacerbations with dexamethasone at a standardized dose compared with a weight-based approach.  .

Methods: This was a single-center, retrospective study of patients ages 2 to 17 years presenting to the pediatric emergency department (ED) with an asthma exacerbation between July 1, 2018, and June 30, 2021. Patients who received at least 1 dose of dexamethasone and had an International Classification of Diseases, 10th revision (ICD-10) code for asthma were included. The primary end point was the rate of return visits to the ED within 30 days and 31 to 90 days. Secondary end points included incidence of hospitalization and intubation, length of stay, dexamethasone dosing discrepancies, other corticosteroids or adjunctive therapies used, and medication escalation at discharge. The incidences of vomiting, hyperglycemia, and hypertension were also evaluated. Descriptive statistics were used for categoric variables and a Kaplan-Meier survival curve and Cox regression evaluated the primary outcome.

Results: A total of 252 patients were included, 162 in the standardized dosing group and 90 in the weight-based group. There was no difference in return visits at 30 days and 31 to 90 days (3.1 vs 4.4, p = 0.58; and 3.7 vs 7.8, p = 0.16). The standardized group had a statistically significant shorter length of stay and lower ipratropium and magnesium use compared with the weight-based group. However, hospitalization rates were lower overall in the weight-based group. The incidences of vomiting, hyperglycemia, and hypertension were similar.

Conclusions: A standardized dosing strategy for dexamethasone in pediatric asthma exacerbations showed favorable outcomes and may lead to improved adherence.

With a limited number of child and adolescent psychiatrists available to see youth patients, many common psychiatric problems in youth are managed by other providers. Clinical pearls from experts in child and adolescent psychiatry can help general practitioners with this management. Some common issues are discussed here for which practical guidance is offered, ranging from approaches to assessment and how to start and titrate medications for the treatment of attention deficit hyperactivity disorder, depression, and sleep problems.

Objective: Limited data exist comparing indomethacin and ibuprofen for the treatment of patent ductus arteriosus (PDA). The objective was to compare the safety and efficacy of indomethacin and ibuprofen for treatment of PDA closure.

Methods: This single-center, pre-test/post-test quasi-experiment included preterm infants admitted to the neonatal intensive care unit who received indomethacin (July 1, 2013-September 30, 2015) or ibuprofen (December 1, 2015-July 31, 2019) for PDA. Patients were excluded if they were thrombocytopenic, had existing kidney injury, unresolved intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC) at treatment initiation. Data were obtained from the electronic health record. Study outcomes were complete PDA closure, degree of PDA closure, resolution of symptoms, and new-onset acute kidney injury (AKI), IVH, or NEC.

Results: A total of 114 patients were included: 44 (39%) received indomethacin and 70 (61%) received -ibuprofen. Twenty-one (21%) patients experienced successful PDA closure within 1 week: 13 (32%) indomethacin patients and 8 (13%) ibuprofen patients (p = 0.023). PDA size reduction occurred in 43 (46%) patients with 29 (25%) experiencing complete symptom resolution. Significantly more indomethacin patients compared with ibuprofen patients experienced new-onset AKI (48% vs 17%; p < 0.001) and received concomitant nephrotoxins (68% vs 39%; p = 0.002). There were no significant differences in new-onset IVH or NEC.

Conclusions: Indomethacin administration successfully closed the PDA in more neonates than ibuprofen but resulted in higher rates of AKI. However, this was confounded by more frequent administration of concomitant nephrotoxins. Larger trials are needed to help elucidate the optimal drug for closure of the PDA in neonates.

Fibrinogen deficiencies in neonates can lead to bleeding complications. In this report, we describe a case of congenital afibrinogenemia in a newborn with critical pulmonary stenosis who presented with bilateral cephalohematomas after an uncomplicated delivery. The initial use of cryoprecipitate was followed by administration of fibrinogen concentrate. We estimated a half-life of 24 to 48 hours with the concentrate product. This patient received fibrinogen replacement and had a subsequent successful cardiac repair. The drug's shorter half-life in this neonate contrasts with prior reports of longer half-life in older patients and is important to note in treating future neonatal patients with this diagnosis.

Objective: The aim of our study was to evaluate the frequency, type, and risk factors associated with adverse drug reactions (ADRs) in HIV-positive children with adherence to antiretroviral therapy (ART) at the Unit of Care and Accompaniment for People Living With HIV (USAC) of Bamako.

Methods: A cross-sectional study was conducted at USAC of Bamako from May 1, 2014, to July 31, 2015. We included children aged 1 to 14 years with at least 6 months of ARV treatment initiated at USAC, with or without ADRs. Data collection was based on information collected from parents and clinical/biological assessments.

Results: Median age of participants was 36 months and female sex was predominant (54.8%). Poor adherence during the study was observed in 15% of cases. Of patients in the study, 52% had a CD4 count less than 350 cells/mm³ at the time of adverse events. In bivariate analysis, we found that participants with adherence to ART tended to be younger than those with non-adherence to ART (36 vs 72 months, p = 0.093). In multivariable analysis, prophylactic treatment was the only factor marginally associated with ART adherence in HIV patients (p = 0.09). No other adverse biological effects or clinical conditions were associated with ART adherence in this study.

Conclusions: In this study we found that ADRs were frequent in HIV-positive patients but less frequent in ART-adherent HIV-positive children. Therefore, it is essential to regularly monitor children receiving ARVs to detect and treat the complications associated with these therapies according to ART adherence.