Thromboembolic Complications in a Pediatric Patient Population: Treatment with Direct Oral Anticoagulants. Monitoring of Treatment Efficiency with D-Dimer Levels and Safety Profile By Thromboelastogram

Direct oral anticoagulants (DOAC) such as the thrombin inhibitor Dabigatran and the coagulation factor Xa inhibitors Apixaban and Rivaroxaban have been in clinical use for the past 5-6 years. Familiarity with their use in the general pediatric population with thrombosis secondary to inflammatory disorders and rheumatologic disease is currently not as prevalent due to the widespread more conventional anticoagulation practice with the fractionated heparins in particular Lovenox. In this report we would like to summarize our experience in a pediatric patient population ranging from 3- 17 years with thrombotic disease. Of 55 patients with various thrombotic events 16 patients were treated with DOAC. There were 5 patients who had underlying inflammatory disease including COVID. Thrombotic complications included arterial as well as venous thrombotic events. All patients had elevated D-Dimer levels ranging from 360-4000 mcg/ml on diagnosis and normalized with successful anticoagulation. All patients had resolution of thrombosis. Thrombelastogram (TEG) were obtained on isolated patients during therapy and were useful to balance anticoagulation to prevent hemorrhagic complications. In conclusion, DOAC are a safe and effective alternative to LMW Heparin in pediatric patients with arterial or venous thrombosis. Monitoring should include determination of D-Dimer levels for efficacy of treatment and TEG in cases with arterial disease where bleeding may be a secondary complication of therapy. Disclosures No relevant conflicts of interest to declare.

Modeling of levothyroxine in newborns and infants with congenital hypothyroidism: challenges and opportunities of a rare disease multi-center study

Modeling of retrospectively collected multi-center data of a rare disease in pediatrics is challenging because laboratory data can stem from several decades measured with different assays. Here we present a retrospective pharmacometrics (PMX) based data analysis of the rare disease congenital hypothyroidism (CH) in newborns and infants. Our overall aim is to develop a model that can be applied to optimize dosing in this pediatric patient population since suboptimal treatment of CH during the first 2 years of life is associated with a reduced intelligence quotient between 10 and 14 years. The first goal is to describe a retrospectively collected dataset consisting of 61 newborns and infants with CH up to 2 years of age. Overall, 505 measurements of free thyroxine (FT4) and 510 measurements of thyrotropin or thyroid-stimulating hormone were available from patients receiving substitution treatment with levothyroxine (LT4). The second goal is to introduce a scale/location-scale normalization method to merge available FT4 measurements since 34 different postnatal age- and assay-specific laboratory reference ranges were applied. This method takes into account the change of the distribution of FT4 values over time, i.e. a transformation from right-skewed towards normality during LT4 treatment. The third goal is to develop a practical and useful PMX model for LT4 treatment to characterize FT4 measurements, which is applicable within a clinical setting. In summary, a time-dependent normalization method and a practical PMX model are presented. Since there is no on-going or planned development of new pharmacological approaches for CH, PMX based modeling and simulation can be leveraged to personalize dosing with the goal to enhance longer-term neurological outcome in children with the rare disease CH.

LGG-30. TRAMETINIB-ASSOCIATED HYPONATREMIA IN A CHILD WITH LOW GRADE GLIOMA IS NOT SEEN FOLLOWING TREATMENT WITH ALTERNATIVE MEK INHIBITOR

Molecularly targeted therapy with MEK inhibitors is increasingly being incorporated into the treatment of pediatric low-grade gliomas (LGGs). Trametinib is an orally available MEK1/2 inhibitor that has demonstrated tumor control in LGGs with BRAF alterations. Safe expansion of MEK inhibitor therapy within the pediatric patient population demands adequate understanding of and surveillance for potential MEK-inhibitor specific toxicities, especially among young children. Hyponatremia has been reported in adult patients receiving BRAF/MEK inhibitor combination treatment as well as in two pediatric patients with known diabetes insipidus treated with trametinib monotherapy. To our knowledge, single-agent trametinib has not previously been reported to be associated with hyponatremia in children in the absence of an underlying endocrinopathy. We present a case of hyponatremia associated with trametinib use in an infant with progressive LGG without known endocrine dysfunction, which recurred after significant dose reduction. Therapy with an alternative MEK1/2 inhibitor, binimetinib, provided excellent tumor response without hyponatremia. Hyponatremia is a rare but serious side effect of trametinib, even without underlying pituitary dysfunction. Infants and patients lacking the ability to quickly regulate fluid intake in response to osmolality changes are at particular risk of suffering severe consequences from hyponatremia and should be monitored closely with initiation of trametinib. Switching to a different drug within the same class may offer an alternative to significant dose reduction or discontinuation due to this toxicity.

1355. Resistance in Gram-Negative Bacteria in the Pediatric Patient Population by Age and Sex

Background Previous research within the Beaumont Infectious Diseases Research Program found an overall increase in antibiotic resistance in adult males versus females. Furthermore, there is a peak in resistance in 18-29-year-old males, not seen in females. The origin of this early peak of antibiotic resistance in adults is unclear. This study examines these trends in the pediatric patient population. Methods Resistance data for all Gram-negative bacterial clinical isolates from Beaumont Health System’s clinical microbiology lab between October 1st, 2010, and December 31st, 2014 was analyzed. The pediatric isolates were categorized into sextiles (0-2, 3-5, 6-8, 9-11, 12-14, 15-17) and the sensitivities for each antibiotic were compared based on gender and age and separated by urine isolates vs. non-urine isolates to account for potential bias based on an abundance of urine samples in females. Results There were 7878 pediatric Gram-negative bacterial isolates in the database, and 96 duplicate samples were removed, leaving 7782 isolates to be analyzed. There were more female isolates (n=6888) than male isolates (n=890) due to the preponderance of urine cultures in females. At most age ranges, antibiotic resistance was significantly higher in males than females. In males, antibiotic resistance was highest between 12-14 and 15-17 years old. When analyzing the cultures based on sample type, the peak in resistance in males is seen in urine isolates, but the patterns of resistance are chaotic in non-urine isolates. This is likely attributable to a low number of isolates. Conclusion Sex is an important factor in determining antibiotic resistance in the pediatric patient population, as males exhibit higher resistance. The peak in antibiotic resistance initially noted in 18-29-year-old males in previous research originates in the pediatric age group and appears to develop between 12-17 years old. Further research is needed to determine the cause of the observed gender bias, to ascertain if it is modifiable in order to reduce antibiotic resistance. Disclosures All Authors: No reported disclosures

Electrospun Orodispersible Films of Isoniazid for Pediatric Tuberculosis Treatment

Child-appropriate dosage forms are critical in promoting adherence and effective pharmacotherapy in pediatric patients, especially those undergoing long-term treatment in low-resource settings. The present study aimed to develop orodispersible films (ODFs) for isoniazid administration to children exposed to tuberculosis. The ODFs were produced from the aqueous solutions of natural and semi-synthetic polymer blends using electrospinning. The spinning solutions and the resulting fibers were physicochemically characterized, and the disintegration time and isoniazid release from the ODFs were assessed in simulated salivary fluid. The ODFs comprised of nanofibers with adequate thermal stability and possible drug amorphization. Film disintegration occurred instantly upon contact with simulated salivary fluid within less than 15 s, and isoniazid release from the ODFs in the same medium followed after the disintegration profiles, achieving rapid and total drug release within less than 60 s. The ease of administration and favorable drug loading and release properties of the ODFs may provide a dosage form able to facilitate proper adherence to treatment within the pediatric patient population.

I Have an Owie!!!

Acute pain in the pediatric patient population is a frequently encountered clinical issue and presenting symptom. Prompt attention to, assessment of, and management of a pediatric patient’s pain are critical in order to enable providers to carry out the necessary diagnostic evaluation and enact the appropriate therapeutic interventions in a timely fashion. This also allows for rapport building between the provider and patients and engenders more trust, compassion, and benevolent care. The pediatric population is unique, both physiologically and developmentally, and therefore, approaches to management of acute pain in these patients must be unique as well. This chapter addresses and discusses assessment of acute pain, including pain scores, and modalities for control of acute pain in pediatric patients.

Is the Laparotomy Here to Stay? A Review of the Disadvantages of Laparoscopy

Minimally invasive procedures have seen increasing utilization in the pediatric patient population since the 1990s. Most thoracic and abdominal operations in pediatric surgery can be performed in a minimally invasive manner including those performed in neonates and infants. Thoracoscopic or laparoscopic operations can reduce hospital length of stay, minimize postoperative pain, and lead to more aesthetic results. However, it is important to be aware of the inherent risks, limitations, and adverse effects associated with these thoracoscopic and laparoscopic techniques, particularly in special populations. In this article, we will review the risks and limitations of laparoscopy in pediatric patients such as cost, operative time, reduced effectiveness, air embolism, hypercarbia, hypothermia, and access-related injuries.