Transcutaneous auricular vagus nerve stimulation may benefit from the addition of N-acetylcysteine to facilitate motor learning in infants of diabetic mothers failing oral feeds.

Objective: This 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. Methods: We 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. Results: NAC 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. Conclusion: In 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.

Suicide-Related Out-of-Hospital Cardiac Arrests in Queensland, Australia: Temporal Trends of Characteristics and Outcomes over 14 Years.

BACKGROUND: Research into suicide-related out-of-hospital cardiac arrests (OHCA) using OHCA registries is scant. A more complete understanding of methods, patient characteristics, and outcomes is essential to inform prehospital management strategies and public health interventions. METHODS: Included were all OHCA attended by Queensland Ambulance Service (Australia) paramedics between 1 January 2007 and 31 December 2020, where suicide-related causes could be identified. Age- and sex-standardized incidence rates were calculated. Suicide methods, patient characteristics, and survival outcomes were described. Factors associated with survival outcomes were investigated. RESULTS: Seven thousand three hundred and fifty-six suicide-related OHCA cases were included. The incidence rates increased from 9.0 per 100,000 population in 2007 to 12.4 in 2020. The incidence rates for males were four times those for females; however, incidence rates for females have increased faster than for males. Hanging was the most common suicide method (63%). Twenty-three percent of patients received resuscitation attempts by paramedics. Among those, the rates of return of spontaneous circulation (ROSC) sustained to hospital arrival, survival to hospital discharge, and survival to 30 days were 28.6, 8.5, and 8.0%, respectively. Over time, the rates of ROSC upon hospital arrival increased, whereas the rates of survival to discharge and 30-day survival remained stable. CONCLUSION: The incidence of prehospital-identified suicide-related OHCA in Queensland has increased over time. The prognosis of suicide-related OHCA is poor. Prevention measures should focus on early identification and treatment of individuals having a high risk of suicide. Emergency medical services need to have sufficient training for telecommunicators and paramedics in suicide risk assessment and identification.

Successful Eradication of a Highly Resistant Elizabethkingia anophelis Species in a Premature Neonate With Bacteremia and Meningitis.

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.

Annual Prevalence of Opioid Receipt by South Carolina Medicaid-Enrolled Children and Adolescents: 2000-2020.

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.

First hepatitis B vaccine uptake in neonates prior to and during the COVID-19 pandemic.

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 vaccination has been further complicated by the COVID-19 pandemic, with decreased uptake of many vaccines. 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 erythromycin 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.

The Impact of 2 Weight-Based Standard Parenteral Nutrition Formulations Compared With One Standard Formulation on the Incidence of Hyperglycemia and Hypernatremia in Low Birth-Weight Preterm Infants.

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.

Opioids or Steroids for Pneumonia or Sinusitis.

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.

Evaluating the Potential Severity of Look-Alike, Sound-Alike Drug Substitution Errors in Children.

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.

Potential Acetaminophen and Opioid Overdoses in Young Children Prescribed Combination Acetaminophen/Opioid Preparations.

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.

Opioid Prescribing and Potential Overdose Errors Among Children 0 to 36 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.

Antenatal pharmacokinetics and placental transfer of N-acetylcysteine in chorioamnionitis for fetal neuroprotection.

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.

Antibiotic timing in neonates with suspected hospital-acquired infections.

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.

An advanced clinical track within a doctor of pharmacy program.

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.

Survey of colleges of pharmacy to assess preparation for and promotion of residency training.

OBJECTIVE: To assess the prevalence of curricular programs or other structured activities designed to prepare students for and to promote residency training. METHODS: An electronic survey instrument containing 12 questions regarding institutional demographics and activities related to pharmacy student preparation for residency training was sent to administrators of all US colleges and schools of pharmacy. RESULTS: Ninety-one survey instruments were e-mailed to US colleges and schools of pharmacy administrators, and an overall response rate of 78% was attained. Twenty-two percent of respondents identified a structured curricular program to prepare students for postgraduate training. In addition, informal programs or informational sessions varying in scope and content were offered by many colleges and schools to prepare students for residency training. CONCLUSION: Many of the US colleges and schools of pharmacy reported structured activities or programs that promote residency training to students. Ten programs had a designated clinical-track curriculum.

Gabapentin therapy for pain and irritability in a neurologically impaired infant.

Gabapentin is a gamma-aminobutyric acid analog used for numerous neurologic conditions, including neuropathic pain and epilepsy. We describe a 39-week gestational age, male infant with hypotonicity, functional short gut, and microduplication of chromosome 22 who was treated with gabapentin to control pain and irritability. During his hospitalization, the infant experienced multiple complications including respiratory distress, persistent pulmonary hypertension of the newborn, hypocalcemia, hypoglycemia, hyperbilirubinemia, gastroesophageal reflux, necrotizing enterocolitis, and cholestatic jaundice. Pain associated with related invasive procedures and surgeries was treated with intermittent and scheduled morphine. In addition to postoperative and procedural pain, the infant continued to experience pain and irritability attributed to neurologic impairment, presumably secondary to his chromosomal abnormality. Trials of scheduled lorazepam along with intermittent morphine and phenobarbital were unsuccessful in managing these symptoms. After failure of nonpharmacologic treatment and continued trials of sedatives and analgesics, gabapentin 5 mg/kg at bedtime was started on day of life 98. Improvement in the infant's tone and disposition was noted by numerous health care professionals and the infant's mother. In addition, the infant's pain scores, using the Pain Assessment in Neonates Scale, showed marked improvement. The infant continued to receive gabapentin; the dosage was increased to 10 mg/kg at bedtime after 6 days, then to 5 mg/kg in the morning and 10 mg/kg at bedtime 10 days later. When the infant was 7 months old, his mother requested that gabapentin be discontinued. He was slowly weaned, and the drug was discontinued when he was 11 months old. The infant tolerated gabapentin well except for experiencing nystagmus, which was noted 31 days after starting the drug and resolved after drug discontinuation. Clinicians should be aware of gabapentin as an alternative treatment for pain and irritability in neurologically impaired infants. Further study is needed, however, to verify the drug's safety and efficacy in neonates and infants. Standardized pain scales along with close patient monitoring will help to guide clinicians in dosage titration to optimize therapy.

Research in women and special populations.

The American College of Clinical Pharmacy charged a Task Force on Research in Special Populations to review, update, and broaden its 1993 White Paper on Women as Research Subjects. Participants of the task force included pharmacy clinicians and investigators in the field. This resulting White Paper, Research in Women and Special Populations, discusses the current concepts regarding the conduct of research in women, as well as in special populations such as children, elderly, minorities, cognitively impaired, and other vulnerable populations (e.g., prisoners and refugees). For each specific population, the barriers to research participation, current guidelines and regulations, and available recommendations to address these barriers are discussed. The participation in research by these populations requires addressing special social and ethical challenges. Clinical pharmacy researchers should be cognizant of these guidelines and be an advocate for the inclusion and the rights of women and special populations in research participation.