When parenteral nutrition is the answer: The case of pediatric intestinal rehabilitation.

In pediatric patients with intestinal failure, parenteral nutrition is lifesaving but also has several associated risks. The goals of intestinal rehabilitation include promoting growth, minimizing complications associated with intestinal failure, and reaching enteral autonomy, if possible. Pediatric intestinal rehabilitation programs are interdisciplinary teams that strive to provide optimal care for children dependent on parenteral nutrition. The provision of parenteral nutrition requires close monitoring of patients' growth, nutrition concerns, clinical status, and laboratory parameters. Recent advances in the field of intestinal rehabilitation include new lipid emulsions, considerations regarding enteral feeding, advances in micronutrient provision, and central venous catheter preservation techniques. Challenges in the field remain, including improving overall quality of life with home parenteral nutrition administration and preventing recently recognized complications such as chronic intestinal inflammation.

Clinical course and therapeutic trial for a case of congenital secretory diarrhea due to novel GUCY2C variant.

Chronic diarrhea presents a significant challenge for managing nutritional and electrolyte deficiencies, especially in children, given the higher stakes of impacting growth and developmental consequence. Congenital secretory diarrhea (CSD) compounds this further, particularly in the case of the activating variants of the guanylate-cyclase 2C (GUCY2C) gene. GUCY2C encodes for the guanylate-cyclase 2C (GC-C) receptor that activates the downstream cystic fibrosis transmembrane receptor (CFTR) that primarily drives the severity of diarrhea with an unclear extent of influence on other intestinal channels. Thus far, management for CSD primarily consists of mitigating nutritional, electrolyte, and volume deficiencies with no known pathophysiology-driven treatments. For activating variants of GUCY2C, experimental compounds have shown efficacy in vitro for direct inhibition of GC-C but are not currently available for clinical use. However, Crofelemer, a CFTR inhibitory modulator with negligible systemic absorption, can theoretically help to treat this type of CSD. Herein, we describe and characterize the clinical course of a premature male infant with a de novo missense variant of GUCY2C not previously reported and highly consistent with CSD. With multi-disciplinary family-directed decision-making, a treatment for CSD was evaluated for the first time to our knowledge with Crofelemer.

Evaluation of potential cost savings through chemotherapy and biotherapy dose-rounding at a pediatric institution.

INTRODUCTION: Rapidly increasing costs of medication acquisition can pose a challenge for health-system pharmacy budgets. The impact of dose-rounding in a pediatric oncology population has not previously been well documented and a retrospective review was undertaken to quantify the potential cost benefits. METHODS: A retrospective chart review of patients with an oncologic diagnosis was performed for cytotoxic agents, asparaginase products, and biotherapy administered between January 1, 2014, and December 31, 2017. In the analysis, orders that could be rounded down to the nearest vial size by 5 or 10% were included. Medication pricing information was based on wholesale acquisition cost (WAC) and was provided by the Department of Pharmacy. Cost savings per medication were determined by multiplying the WAC of the medication by the number of vials saved. RESULTS: Over a 4-year span, 347 patients were evaluated and 552 out of a possible 3110 orders (17.7%) met criteria for a theoretical cost savings of approximately $1,126,000 (∼$3200 per patient). Rounding down doses by up to 5% resulted in a potential savings of about $529,000. When rounding was extended to 5-10% of the originally ordered dose, an additional $597,000 of approximate cost savings could have been realized. The medications with the largest impact on cost savings were rituximab, pegaspargase, and erwinia asparaginase. CONCLUSIONS: For pediatric oncology patients, there exists a unique potential cost savings opportunity if doses are rounded down within 5 or 10% of the originally ordered weight-based or body surface area-calculated dose.

Tolerability and Efficacy of a 1-Bag Pegaspargase Densensitization Protocol in Pediatric Oncology Patients.

Desensitization to pegaspargase has been previously attempted in patients who have a hypersensitivity reaction to pegaspargase when Erwinia asparaginase is not an available alternative because of supply issues. Often, these desensitizations have utilized a 3-bag method to complete the infusion. Retrospective chart review was utilized to evaluate the tolerability and efficacy of a 1-bag method for pegaspargase densensitization at a single center. Pegaspargase was infused over ∼3 hours with increases to the infusion rate every 15 minutes. Fifteen pediatric patients received a total of 28 pegaspargase infusions utilizing a 1-bag method. In total, 23 of the infusions were able to be successfully completed without signs of hypersensitivity reactions. In addition, 9 of the 15 patients were able to both successfully complete all infusions during the study period and have asparaginase levels within the therapeutic range 7 to 14 days after the infusion. Four of the 5 patients that did experience a hypersensitivity reaction were able to complete the infusion, however, none of these patients had acceptable asparaginase levels postinfusion. No patient required intubation or advanced life support measures secondary to anaphylaxis. Overall, the pegaspargase method described here was successful and well tolerated in a majority of patients.

Stability Determination of an Extemporaneously Compounded Ambrisentan Suspension by High Performance Liquid Chromatography Analysis.

OBJECTIVE: Ambrisentan, an endothelin receptor antagonist FDA-approved for the treatment of pulmonary arterial hypertension in adult patients, lacks an acceptable pediatric dosage form. The objective of this investigation was to determine the stability of an extemporaneously compounded ambrisentan suspension. METHODS: Ambrisentan suspension was compounded to a concentration of 1 mg/mL using commercially available suspending agents. The suspension was then evenly split into 2 plastic amber prescription bottles. One bottle was stored at room temperature and under continuous fluorescent light while the other bottle was stored under refrigeration and protection from light. A fast and selective reversed-phase high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of ambrisentan. HPLC analysis was performed on samples withdrawn from the stock bottles at predetermined time intervals, up to 90 days. RESULTS: The developed HPLC method enabled the elution and detection of ambrisentan peak at 4.4 minutes. HPLC analysis revealed that all samples from both storage conditions retained >90% potency throughout the study timeframe. There were no signs of any ambrisentan breakdown products on HPLC analysis. Color and odor of the final product was also consistent throughout the 90-day storage period. CONCLUSION: Ambrisentan suspension, compounded to 1 mg/mL, is stable at room temperature or under refrigeration for up to 90 days.

Comparison of Morphine- and Hydromorphone-Containing Patient-Controlled Epidural Analgesia Solutions in Pediatric Postoperative Patients.

OBJECTIVE: The use of patient-controlled epidural analgesia (PCEA) in pediatric patients has been shown to be safe and effective in managing postoperative pain in children. However, the optimal opioid to use in the epidural regimen remains undetermined. Morphine, hydromorphone, and fentanyl have been the agents most often used, but comparison of effectiveness across studies is difficult. The goal of this study was to compare postoperative pain scores in patients receiving PCEA solutions that contained either ropivicaine plus morphine or ropivicaine plus hydromorphone. METHODS: Retrospective chart review was used at a single center to identify pediatric patients between the ages of 5 and 17 years who used a morphine- or hydromorphone-containing PCEA solution postoperatively during an 18-month period. Maximum pain scores were recorded during 2 consecutive 24-hour periods postoperatively. The primary outcome was the number of patients who had a maximum pain score of ≤4 on postoperative day zero and postoperative day 1. RESULTS: Forty-six patients met the inclusion criteria and were analyzed. Patients prescribed morphine-containing PCEAs had a significantly higher incidence of maximal pain scores ≤4 in the 48 hours immediately after surgery compared with those patients prescribed hydromorphone-containing PCEAs (p = 0.03). Ropivicaine dosing in the epidural solution did not have a significant effect on pain scores and was not statistically different between opioid groups. Pediatric patients were able to effectively use the PCEA on-demand dose, with patients having pain scores >4 demanding significantly more on-demand doses from the PCEA than those patients with pain scores ≤4 (p ≤ 0.002). No serious adverse events were reported. CONCLUSIONS: Morphine-containing PCEAs may have an advantage in controlling postoperative pain in pediatric patients compared with hydromorphone-containing PCEAs. However, the heterogeneous nature of the procedures performed and the small sample size limit the generalizability of this study.