ObjectiveThis study aims to determine if pretreating with enteral N-acetylcysteine (NAC) improves CNS oxidative stress and facilitates improvement in oromotor skills during transcutaneous auricular nerve stimulation (taVNS) paired with oral feedings in infants of diabetic mothers (IDMs) who are failing oral feeds.MethodsWe treated 10 IDMs who were gastrostomy tube candidates in an open-label trial of NAC and taVNS paired with oral feeding. NAC (75 or 100 mg/kg/dose) was given by nasogastric (NG) administration every 6 h for 4 days, then combined with taVNS paired with 2 daily feeds for another 14 days. NAC pharmacokinetic (PK) parameters were determined from plasma concentrations at baseline and at steady state on day 4 of treatment in conjunction with magnetic resonance spectroscopic (MRS) quantification of CNS glutathione (GSH) as a marker of oxidative stress. We compared increases in oral feeding volumes before and during taVNS treatment and with a prior cohort of 12 IDMs who largely failed to achieve full oral feeds with taVNS alone.ResultsNAC 100 mg/kg/dose every 6 h NG resulted in plasma [NAC] that increased [GSH] in the basal ganglia with a mean of 0.13 ± 0.08 mM (p = 0.01, compared to baseline). Mean daily feeding volumes increased over 14 days of NAC + taVNS compared to the 14 days before treatment and compared to the prior cohort of 12 IDMs treated with taVNS alone. Seven IDMs reached full oral feeds sufficient for discharge, while three continued to have inadequate intake.ConclusionIn IDM failing oral feeds, NAC 100 mg/kg/dose every 6 h NG for 4 days before and during taVNS paired with oral feeding increased CNS GSH, potentially mitigating oxidative stress, and was associated with improving functional feeding outcomes compared to taVNS alone in a prior cohort. This represents a novel approach to neuromodulation and supports the concept that mitigation of ongoing oxidative stress may increase response to taVNS paired with a motor task.

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme involved in the Phase I metabolism of numerous medications used in clinical practice. Its potential significance in pediatric pharmacotherapy is underscored by the unique metabolic profile of children, which differs markedly from adults, especially in neonates, infants, and young children due to developmental changes in enzyme activity. This review explores the critical role of CYP3A4 in the metabolism of drugs used in the pediatric population, with a particular focus on combination drug therapies. Given the high potential for drug-drug interactions in combination therapies, understanding the modulation of CYP3A4 activity is essential for optimizing therapeutic outcomes and minimizing adverse effects. This paper further examines the structural similarities between these medications and bergamottin, a known CYP3A4 inhibitor found in citric fruits such as grapefruit. Variability in CYP3A4 activity, influenced by genetic polymorphisms, developmental stage, and external factors, necessitates careful consideration in the prescribing and management of drugs in children. This review corroborates the need for personalized medicine approaches and enhanced pharmacovigilance to ensure the safe and effective use of CYP3A4-metabolized drugs in the pediatric population.

Introduction: Routine vaccination for hepatitis B is recommended at birth, and most infants should be vaccinated within 24 h of life. Historically, vaccination rates have been less than ideal, and routine vac-cination has been further complicated by the COVID-19 pandemic, with decreased uptake of many vac-cines. This retrospective study assessed hepatitis B vaccination rates at birth before and after the start of the COVID-19 pandemic and explored the factors associated with lower vaccination rates. Methods: Infants born at a single academic medical center in Charleston, South Carolina from November 1, 2018 through June 30, 2021 were identified. Infants were excluded if they died or received >= 7 days of systemic steroid therapy within the first 37 days of life. Maternal and infant baseline characteristics and uptake of the first hepatitis B vaccine during hospital admission were recorded. Results: A total of 7808 infants were included in the final analysis, with an overall vaccine uptake of 91.6 %. Of the 3880 neonates in the pre-pandemic group, 3583 (92.3 %) were vaccinated, versus 3571 (90.9 %) of 3928 neonates in the pandemic group (rate difference = 1.4 %; 95 % confidence interval-2.8 % to 5.7 %, p = 0.52). Factors independently associated with lower vaccine uptake included being of non-Hispanic white race, born to a married mother, birth weight < 2 kg, and parental refusal of ery-thromycin eye ointment at birth. Conclusion: The COVID-19 pandemic did not significantly affect the uptake of inpatient neonatal hepatitis B vaccination. Several patient-specific factors were associated with suboptimal vaccination rates in this population.(c) 2023 Elsevier Ltd. All rights reserved.

Introduction: taVNS improves oral feeding in newborns who are failing oral feeds but is ineffective in Infants of Diabetic Mothers (IDM) with lower CNS glutathione(GSH) concentrations in a prior trial. We hypothesized that mitigating oxidative stress with N-acetylcysteine(NAC) prior to taVNS would enhance motor learning in IDM and achieve full oral feeds. We measured PK and CNS GSH changes with NAC. Methods: Following informed consent, we enrolled 8 IDM slated to receive gastrotomy tubes. Infants received NAC 75 (n=4) or 100mg/kg/dose q6h (n=4) via nasogastric tube prior to feeds for 4 days alone, then with taVNS for up to 14 days. We obtained magnetic resonance spectroscopy (MRS) before NAC, after 4d of NAC, and the end of treatment, along with steady-state NAC serum concentrations for PK estimates around day 4 MRS. Feeding volumes were compared between IDM treated with NAC+taVNS (n=8) and taVNS alone (prior trial, n=12). Results: Mean (SD) postmenstrual age was 41±1wks, days attempting po were 39±8d, and 50% infants had CNS bleeds and infarcts due to birth asphyxia. The increase in daily oral feeds over 2 weeks was significantly greater during NAC+taVNS (+2.6ml/kg/d) than prior to treatment (0.5ml/kg/d, p<0.001) and greater than during taVNS alone (+1.5ml/kg/d, p<0.001). 62% IDM reached full oral feeds with NAC+taVNS, compared with 25% with taVNS alone. PK parameters included t½ = 1.8±0.4hours, AUC= 58.7±26.3 mcg-hr/mL, and CL= 1107±257mL/hr/kg. MRS showed increased [GSH] in basal ganglia in all infants at 1.5-2h after ng NAC. NAC was well tolerated. Conclusions: NAC improved CNS antioxidant status and facilitated taVNS effects on oral feeding volumes in Infants of Diabetic Mothers who have oxidative stress and largely did not respond to taVNS alone. This approach may enhance neuromodulation effects in other CNS neuroinflammatory conditions. Research Category and Technology and Methods Translational Research: 12. Vagus Nerve Stimulation (VNS); Keywords: NAC, taVNS, CNS oxidative stress, infants of diabetic mothers

•As-needed use of ICS-formoterol has not been well implemented in patients with asthma. •Might be a lack of awareness of the updated recommendations from GINA report. •Insurance coverage of as-needed ICS-formoterol may be limited by its off-label use. •Areas for improvement available for pharmacist and other healthcare professionals to improve the implementation.

Elizabethkingia anophelis is a Gram-negative bacillus that can exhibit highly resistant phenotypes against most antibiotics with evidence of efficacy and safety in the neonatal population. Given the limited antimicrobial options, clinicians may be forced into challenging treatment scenarios when faced with central nervous system infections in premature neonates caused by E. anophelis . We report a case of successful treatment of hospital-acquired meningitis and bacteremia caused by E. anophelis at 11 days of life in a male infant born at 29 weeks, 1 day gestation and birth weight of 1.41 kg. Therapy consisted of vancomycin, dose adjusted to maintain goal troughs of 15-20 mg/L, and rifampin 10 mg/kg/dose every 12 hours, with ciprofloxacin 15 mg/kg/dose every 12 hours and trimethoprim/sulfamethoxazole 5 mg/kg/dose every 12 hours added due to antimicrobial susceptibilities and unsatisfactory response, for a total of 21 days. Following initiation of this multidrug regimen, repeat cultures were negative, laboratory parameters improved [with exception of elevated cerebrospinal fluid (CSF) white blood cell count], the patient remained otherwise stable, and there were no adverse effects noted from therapy. Complications after treatment included the requirement of bilateral hearing aids and the development of hydrocephalus necessitating ventriculoperitoneal shunt placement. To our knowledge, we report the first case of meningitis in a premature neonate initially identified as E. anophelis in the United States treated with this regimen which led to successful microbiologic eradication with no antimicrobial safety concerns.

Understanding patterns of opioid receipt by children and adolescents over time and understanding differences between age groups can help identify opportunities for future opioid stewardship. We conducted a retrospective cohort study, using South Carolina Medicaid data for children and adolescents 0–18 years old between 2000–2020, calculating the annual prevalence of opioid receipt for medical diagnoses in ambulatory settings. We examined differences in prevalence by calendar year, race/ethnicity, and by age group. The annual prevalence of opioid receipt for medical diagnoses changed significantly over the years studied, from 187.5 per 1000 in 2000 to 41.9 per 1000 in 2020 (Cochran–Armitage test for trend, p < 0.0001). In all calendar years, older ages were associated with greater prevalence of opioid receipt. Adjusted analyses (logistic regression) assessed calendar year differences in opioid receipt, controlling for age group, sex, and race/ethnicity. In the adjusted analyses, calendar year was inversely associated with opioid receipt (aOR 0.927, 95% CI 0.926–0.927). Males and older ages were more likely to receive opioids, while persons of Black race and Hispanic ethnicity had lower odds of receiving opioids. While opioid receipt declined among all age groups during 2000–2020, adolescents 12–18 had persistently higher annual prevalence of opioid receipt when compared to younger age groups.

Background: As survival rates in neonates with congenital heart disease have improved, research has shown they are at an increased risk for brain injury and neurodevelopmental delay. One intervention shown to have a positive impact on the development in premature and full-term newborns, as well as a positive impact on mother-infant relationship, is kangaroo care (KC). There is limited evidence to support the use of KC in infants with congenital heart disease, some of who may also be premature. Purpose: The purpose of this study was to examine the safety and feasibility of introducing KC for neonates with congenital heart disease in the pediatric cardiac intensive care unit. Methods: A descriptive observational feasibility study was employed to evaluate the safety and efficacy of KC for this population. Results: There were 25 neonates included with 60 sessions of KC. There were no adverse events including line and tube dislodgments and physiological instability related to the use of KC. Implications for Practice: This study found KC to be safe and feasible for neonates with KC. Implications for Research: This is the first study examining the feasibility and safety of KC in this vulnerable population of neonates. Further research should be conducted using a quasi-experimental design to investigate neurodevelopmental outcomes with a larger sample of patients.

Background: Standardized parenteral nutrition (PN) formulations are used in at-risk neonates to provide nutrition immediately following birth. However, evidence for the optimal formulation(s) to maximize growth while reducing the risks of glucose and electrolyte abnormalities is limited. Purpose: The purpose of this study was to compare the rates of hypernatremia and hyperglycemia with 2 weight-based standardized PN formulations versus one standard PN in low birth-weight preterm neonates. Methods: This was a single-center observational study of infants less than 1800 g birth weight and less than 37 weeks' gestation who received standardized PN in the first 48 hours of life. Patients in the weight-based PN group were compared with a historical group of patients receiving single standard PN. Rates of hypernatremia and hyperglycemia were compared by χ2 analysis. Results: There was a nonsignificant (P = .147) reduction in hypernatremia in the weight-based PN group (9 of 87; 10.3%) compared with the single PN group (16 of 89; 18.0%). However, hyperglycemia was significantly more frequent in the weight-based group than in the single PN group (24.1% vs 12.4%, P = .035). Implications for Practice: The 2 weight-based PN standardized formulations studied did not significantly decrease the incidence of hypernatremia or hyperglycemia. Implications for Research: Future studies to determine optimal standardized PN to provide early nutrition in high-risk neonates are warranted.

OBJECTIVES: To compare the frequency of opioid and corticosteroid prescriptions dispensed for children with pneumonia or sinusitis visits on the basis of location of care. METHODS: We evaluated 2016 South Carolina Medicaid claims data for 5 to 18 years olds with pneumonia or sinusitis. Visits were associated with 1 of 3 locations: the emergency department (ED), urgent care, or the ambulatory setting. RESULTS: Inclusion criteria were met by 31 838 children. Pneumonia visits were more often linked to an opioid prescription in the ED (34 of 542 [6.3%]) than in ambulatory settings (24 of 1590 [1.5%]; P ≤ .0001) and were more frequently linked to a steroid prescription in the ED (106 of 542 [19.6%]) than in ambulatory settings (196 of 1590 [12.3%]; P ≤ .0001). Sinusitis visits were more often linked to an opioid prescription in the ED (202 of 2705 [7.5%]) than in ambulatory settings (568 of 26 866 [2.1%]; P ≤ .0001) and were more frequently linked to a steroid prescription in the ED (510 of 2705 [18.9%]) than in ambulatory settings (1922 of 26 866 [7.2%]; P ≤ .0001). In logistic regression for children with pneumonia, the ED setting was associated with increased odds of receiving an opioid (adjusted odds ratio [aOR] 4.69) or steroid (aOR 1.67). Similarly, patients with sinusitis were more likely to be prescribed opioids (aOR 4.02) or steroids (aOR 3.05) in the ED than in ambulatory sites. CONCLUSIONS: School-aged children received opioid and steroid prescriptions for pneumonia or sinusitis at a higher frequency in the ED versus the ambulatory setting.

In 2018, more than 5,000 individuals participated in the ASHP Resident Matching Program (i.e., the “Match”).1 One of the largest perceived barriers among students who were undecided about pursuing postgraduate training was the belief that their student loans or other financial obligations after graduation would be a significant burden if they entered a postgraduate program.2 Personal finance education that prepares students to manage stress associated with student loan debt is not commonly incorporated into pharmacy curricula.3 An aspect of financial planning and student indebtedness that has not previously been evaluated is the direct financial costs associated with pursuing postgraduate residency training (PGRT) incurred by pharmacy students. In particular, the pre-PGRT application (e.g., costs of preparing and attending the ASHP Midyear Clinical Meeting [MCM], American College of Clinical Pharmacy Annual Meeting, or other regional showcase opportunities), PGRT application, and post-PGRT application (e.g., traveling for onsite interviews) may become added financial burdens.

Opioid analgesics are potentially hazardous medications in young children. During the past 5 years, much attention has been drawn to the safety concerns of these medications.1–6 Data evaluating pain control after injury among older children suggest that opioid drugs are not more effective than nonopioids in treating pain secondary to acute traumatic injury.7,8 Postsurgical data evaluating children who underwent palatoplasty demonstrated that children treated with nonopioid pain regimens did as well as subjects treated with morphine.9 More concerning, opioid analgesics have been consistently demonstrated to be among the most common drugs involved in accidental ingestions prompting emergency department visits and rank consistently high as contributors to medication-related death in children.1 Data from nonopioid medication studies have demonstrated that young children, particularly infants, are at higher risk for experiencing drug errors and experiencing adverse outcomes should they experience a dosing error.10 In previous studies, we demonstrated that children 0 to 36 months old who received opioid drugs received a potential overdose approximately 1.6% to 2.7% of the time, and the frequency of potential opioid overdose may be as high as 11.8% among children 0 to 2 months old.11,12 In this brief report, we examined South Carolina Medicaid data to determine the indications for receipt of opioid analgesics among subjects 0 to <6 months old.

INTRODUCTION:Combination preparations of acetaminophen/opioid are the most common opioid form prescribed to children. We tested the hypothesis that dispensed prescriptions of acetaminophen/opioid preparations more appropriately match acetaminophen dosing parameters than opioid dosing parameters. We also hypothesized that the frequency of potential overdose was inversely related to subject age.METHODS:Using 2011 to 2012 South Carolina outpatient Medicaid data, the authors identified acetaminophen/opioid preparations dispensed to children 0 to 36 months. Utilizing Centers for Disease Control and Prevention (CDC) data to impute subject weights as the 97th percentile for age and gender, the authors used imputed weights to calculate the maximum recommended daily dose (expected dose) of each component. We calculated the dose delivered per day (observed dose) based on drug concentration, volume dispensed, and days' supply and then calculated the frequency of overdose (observed dose/expected dose, >1.10) by each component, comparing overdose frequency of acetaminophen to the overdose frequency of opioid using a risk ratio. Logistic regression evaluated differences in potential overdose by age, controlling for race/ethnicity and gender.RESULTS:Among 2,653 dispensed prescriptions of study drugs to 2,308 children 0 to 36 months old, the frequency of potential overdose was 0.7% for acetaminophen and 1.6% for opioid (risk ratio, 2.28). Age less than 3 months was associated with a greater frequency of potential overdose of either acetaminophen or opioid, even after controlling for gender and race/ethnicity.CONCLUSIONS:Prescriptions of acetaminophen-opioid drugs dispensed to children 0 to 36 months old contained potential overdoses of opioid at greater than twice the frequency of acetaminophen and were more likely to occur in infants less than 3 months old.

Objective. To estimate the frequency of potential overdoses among outpatient opioid-containing prescriptions. Method. Using 11 years of outpatient Medicaid prescription data, we compared opioid dose dispensed (observed) versus expected dose to estimate overdose error frequencies. A potential overdose was defined as any preparation dispensed that was >110% of expected based on imputed, 97th percentile weights. Results. There were 59 536 study drug prescriptions to children 0 to 36 months old. Overall, 2.7% of the prescriptions contained potential overdose quantities, and the average excess amount dispensed was 48% above expected. Younger ages were associated with higher frequencies of potential overdose. For example, 8.9% of opioid prescriptions among infants 0 to 2 months contained potential overdose quantities, compared with 5.7% among infants 3 to 5 months old, 3.6% among infants 6 to 11 months old, and 2.3% among children >12 months (P < .0001). Conclusions. Opioid prescriptions for infants and children routinely contained potential overdose quantities.

Objective Look-alike, sound-alike (LASA) drug name substitution errors in children may pose potentially severe consequences. Our objective was to determine the degree of potential harm pediatricians ascribe to specific ambulatory LASA drug substitution errors. Methods We developed a unified list of LASA pairs from published sources, removing selected drugs on the basis of preparation type (eg, injectable drugs). Using a modified Delphi method over 3 rounds, 38 practicing pediatricians estimated degree of potential harm that might occur should a patient receive the delivered drug in error and the degree of potential harm that might occur from not receiving the intended drug. Results We identified 3550 published LASA drug pairs. A total of 1834 pairs were retained for the Delphi surveys, and 608 drug pairs were retained for round 3. Final scoring demonstrated that participants were able to identify pairs where the substitutions represented high risk of harm for receiving the delivered drug in error (eg, did not receive methylphenidate/received methadone), high risk of harm for not receiving the intended drug (eg, did not receive furosemide/received fosinopril), and pairs where the potential harm was high from not receiving the intended drug and from erroneously receiving the delivered drug (eg, did not receive albuterol/received labetalol). Conclusions Pediatricians have identified LASA drug substitutions that pose a high potential risk of harm to children. These results will allow future efforts to prioritize pediatric LASA errors that can be screened prospectively in outpatient pharmacies.

OBJECTIVE:To determine the pharmacokinetics (PK) and placental transfer of intravenous (i.v.) N-acetylcysteine (NAC) in mothers with a clinical diagnosis of chorioamnionitis (CA) and determine the PK of i.v. NAC in their infants. STUDY DESIGN:In this prospective, double-blind study i.v. NAC 100 mg/kg/dose or saline was administered within 4 hours of CA diagnosis to pregnant women ≥24 weeks' gestation and then every 6 hours until delivery. Maternal PK and placental transfer were determined with maternal blood and matched maternal and cord venous blood. Neonatal PK estimates were determined from i.v. NAC (12.5-25 mg/kg/dose) administered every 12 hours for 5 doses. Noncompartmental analyses were performed for maternal and neonatal PK estimates. RESULTS:Eleven mothers (5 preterm, 6 near-term) and 12 infants (1 set of twins) received NAC. Maternal clearance (CL) of NAC was faster than in nonpregnant adults, with a terminal elimination half-life of 1.2 ± 0.2 hours. The NAC cord to maternal ratio was 1.4 ± 0.8, suggesting rapid placental transfer and slower rate of fetal CL. Neonatal PK estimates for near-term compared with preterm infants showed a significantly shorter terminal elimination half-life (5.1 vs 7.5 hours, respectively) and greater CL (53.7 vs 45.0 mL/h/kg, respectively). CONCLUSIONS:Maternal CL and placental transfer of NAC was rapid, with umbilical cord concentrations frequently exceeding maternal concentrations. The administration of NAC to mothers with CA achieves predictable NAC plasma concentrations in the fetus, indicating that antenatal neuroprotection may be possible for these newborns at high risk for neuroinflammation.

There exists general agreement within neonatology that antibiotics should be administered promptly to neonates with possible bacterial sepsis and meningitis. We initiated a series of quality improvement cycles designed to reduce delays in the initiation of antibiotic therapy to less than 2 hours when hospital-acquired infection (HAI) was suspected. All infants in this study were in neonatal intensive care (level II or III) who were started on antibiotics for a suspected HAI (defined as an infection that occurred 72 hours after admission to the NICU) were audited. Through a series of quality improvement cycles, we analyzed sources of delays in the initiation of antibiotic therapy from the time the order was written through administration. In subsequent cycles, we intervened to reduce delays through education, standardize the evaluation process, and develop an online ordering system that streamlined the workflow patterns in the nurseries and pharmacy. Using a prospective cohort design, we compared antibiotic delivery times after each process improvement cycle. Antibiotic delivery time was reduced from a median of 137.5 minutes to 75 minutes and variation of practice was reduced in terms of standard deviation and range (P < .001). The use of computerized physician order entry significantly improved the writing of STAT orders (P < .0001). A systematic analysis of workflow patterns and efficiencies, coupled with improvement cycles targeting delays and development of a computerized physician order entry system, allowed us to improve antibiotic delivery time in neonates with suspected HAI in an intensive care nursery system.

Purpose: To assess graduating pharmacy students' perceptions of mentorship received during pharmacy school when pursuing post-graduate residency training (PGRT).Methods: A survey was emailed to all Accreditation Council for Pharmacy Education (ACPE) accredited schools of pharmacy inviting graduating pharmacy students pursuing PGRT to evaluate aspects of mentorship. The 18-item survey instrument contained five sections: satisfaction with mentorship in various areas (e.g., interview preparation and selecting programs for application), importance of mentorship, amount of mentorship desired, mentorship programs, and match process results. Incomplete surveys were excluded from analysis. Descriptive statistics were used to summarize responses while Chi-square and Fisher's exact tests were used to compare responses from the matched and non-matched groups. Additionally, regression analysis was conducted to evaluate the students' match results with satisfaction in various areas of mentorship.Results: Complete surveys were received from 268 students attending 39 schools of pharmacy. Students ranked curriculum vita (CV) preparation and establishing residency rank list as the most and least important mentorship activities, respectively. Compared with non-matched students, matched students found mentorship with CV preparation (p = 0.02) and selecting programs to apply to (p = 0.01) significantly more important. In addition, matched students were more satisfied with mentorship on CV preparation (85% vs. 71%, p = 0.02), interviewing (71% vs. 38%, p < 0.001), residency recruitment at meetings preparation (76% vs. 59%, p = 0.03) and selecting programs to apply to (71% vs. 39%, p < 0.001).Conclusion: Graduating pharmacy students pursuing PGRT were most satisfied with CV and residency recruitment at meetings preparation, and along with interview preparation, ranked them as most important. Published by Elsevier Inc.

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Sandra S. Garner, Toby H. Cox; Lucinactant: New and Approved, But Is It an Improvement?. The Journal of Pediatric Pharmacology and Therapeutics 1 December 2012; 17 (3): 206–210. doi: https://doi.org/10.5863/1551-6776-17.3.206 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search nav search search input Search input auto suggest Search

Objective. To evaluate the advanced clinical track, a curricular track designed to prepare doctor of pharmacy (PharmD) students for residency training and institutional practice.Design. The advanced clinical track required completion of elective coursework, an additional advanced practice experience, 8 clinical experiences, and a skills checklist, and participation in a clinical skills competition.Assessment. Thirty-two graduates of the advanced clinical track were surveyed. Of the 23 respondents, 95% of those who pursued residency training were successfully matched with a residency program. Ninety-one percent of respondents felt that the advanced clinical track increased their confidence and 74% felt it was definitely an advantage when applying to a residency program. All participants agreed that the advanced clinical track met their expectations or goals and would recommend it to other students.Conclusion. Completion of an advanced clinical track was viewed by PharmD graduates as valuable preparation for residency training and institutional practice and would be recommended to other students.