Implementation Strategies for Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) to Prevent Neonatal Medication-Induced Kidney Injury.

Acute kidney injury (AKI) is a common complication among patients admitted to the neonatal intensive care unit. Nephrotoxic medications (NTMs) are known to increase the incidence of AKI, but the use of these -medications is often unavoidable. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) is a -quality improvement (QI) project that may be implemented at individual institutions and aims to systematically identify AKI in neonates and infants receiving NTMs. The purpose of this review is to describe nephrotoxic AKI in the neonatal population, introduce the Baby NINJA QI project and its potential to reduce neonatal AKI, and outline strategies for effective implementation of Baby NINJA.

Children's Oncology Group's 2023 blueprint for research: Pharmacy.

Children's Oncology Group (COG) pharmacists and pharmacy technicians from more than 200 COG-member institutions comprise the COG Pharmacy Discipline. Discipline members serve an essential role in the design and execution of COG clinical trials. Core activities include study drug management, study drug access, clinical trial operations, protocol harmonization, and direct patient care. Discipline members are also actively involved in continuing education, membership engagement, and research across other COG committees/domains. Future areas of committed growth for the discipline include pharmacogenomics, pharmacokinetics, pharmacoeconomics, pharmaceutics, and implementation science.

Valproic Acid Serum Concentration and Incidence of Toxicity in Pediatric Patients.

In certain pediatric patients on valproic acid, therapeutic range (50-100 µg/mL) is maximized or exceeded to achieve better seizure control. This study compared incidence of common valproic acid adverse effects (thrombocytopenia, hepatotoxicity, and hyperammonemia) across maintenance concentration and age group. One hundred twenty-four children on maintenance valproic acid between January 2013 and January 2021 were eligible for inclusion. Fifty-six patients were maintained in concentration range 50 to 80 µg/mL, an additional 44 between 80 and 100 µg/mL and 24 between 100 and 120 µg/mL. Forty-one patients were prepubescent, 57 pubescent, and 26 postpubescent. There were no statistically significant differences observed in the primary endpoint of thrombocytopenia across serum concentration range (P = .093) or age group (P = .628). No significant differences in hepatic dysfunction (P = .099) or hyperammonemia (P = .548) were observed in serum concentration groups. Similarly, age group analysis observed no difference in hepatic dysfunction (P = .615) or hyperammonemia (P = .369). Serum valproic acid levels >100 µg/mL can be considered in select pediatric patients based on this study.

Updates in clinical data for FDA-approved disease-modifying therapies for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a rare, diverse group of inherited neuromuscular disorders that cause degradation of the lower motor neurons, progressive muscle atrophy, and weakness. The natural history of SMA has changed significantly with an increased understanding of SMA pathophysiology and new technologies. As a result, affected individuals now have 3 disease-modifying therapies available for treatment. Evidence suggests that these novel agents are more effective when started early in the disease process. This reinforces the importance of newborn screening as a mechanism for early diagnosis. Pharmacists are highly valued members of the healthcare team who play a pivotal role in the SMA care team. Therefore, pharmacists must be up-to-date on SMA's medical management, including the most current efficacy and safety data to assist providers, caregivers, and patients in selecting these agents and ensuring patients with SMA receive optimal and timely medical care.

N-acetylcysteine for Management of Distal Intestinal Obstruction Syndrome.

With the improving life expectancy of cystic fibrosis patients, new manifestations of the disease are emerging. Distal intestinal obstruction syndrome is one of the increasingly noted complications. Traditionally this syndrome was treated surgically. N-acetylcysteine is sometimes used as a non-surgical treatment option despite lack of definitive evidence for its efficacy and safety and not being mentioned in current treatment guidelines. The existing case reports suggest that N-acetylcysteine may have a place in therapy for older patients with incomplete distal intestinal obstruction syndrome to relieve the initial obstruction or following disimpaction to ensure clearance of remaining ileus and to prevent obstruction recurrence. In younger patients (e.g., <3 years of age), efficacy of N-acetylcysteine has been controversial and its use has been associated with drug-induced liver injury and hypernatremia. In the cases included in this review, 4% N-acetylcysteine was the formulation most commonly used. Since higher concentrations have been associated with increased adverse effects and mucosal injury, lower concentrations and dosages should be used when using N-acetylcysteine until further evidence becomes available. Proper administration technique and monitoring parameters are not well defined in current literature. Prospective, well-designed clinical trials are lacking and would be helpful to better define the role of N-acetylcysteine in distal intestinal obstruction syndrome.

Nusinersen: A Novel Antisense Oligonucleotide for the Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) encompasses a group of autosomal recessively inherited degenerative neuromuscular disorders. They range in severity from neonatal onset with rapidly progressive weakness and early mortality (SMA-1), to onset in infancy (SMA-2), to adolescent/adult onset with indolent clinical course (SMA-3/-4). SMA patients share mutations in the survival motor neuron (SMN) gene; variations in clinical phenotypes are attributable to copy numbers of the closely related SMN2 gene. In December 2016, the US Food and Drug Administration (FDA) approved nusinersen (Spinraza, Biogen, Cambridge, MA) to treat SMA. Nusinersen, an antisense oligonucleotide, is administered directly into cerebrospinal fluid. It alters SMN2 pre-RNA splicing so exon 7 is included, increasing expression of functional SMN protein. Although nusinersen was FDA approved for treatment of all forms of SMA, the initial clinical trials were limited to patients up to age 14 years, diagnosed with SMA-1,-2, -3, not on mechanical ventilation support. Two subsequent phase 3 trials were completed for SMA-1 and SMA-2/-3 and demonstrated improved motor milestones and event-free survival, better than expected based on natural history studies. Efficacy assessments for patients receiving nusinersen are based on serial assessments of performance on age-appropriate standardized motor scales. Treatment requires complex financial and logistics because of the very high drug cost, intrathecal administration, and medical fragility of the patients. Treatment implementation also engenders ethical considerations related to cost, insurance coverage, limited clinical data on groups of patients not in clinical trials, and questions of duration of treatment. Nusinersen has been integrated into the treatment of many SMA patients.