Impact of Pharmacogenomics on Pediatric Psychotropic Medication Prescribing in an Ambulatory Care Setting.

Objective: Evidence for pharmacogenomic (PGx) guided treatment in child and adolescent psychiatry is growing. This study evaluated the impact of PGx testing on psychotropic medication prescribing in an ambulatory child and adolescent psychiatry and a developmental pediatrics clinic. Methods: This was a single-center, retrospective, descriptive analysis of patients who underwent PGx testing between January 2015 and October 2022 at a child and adolescent psychiatry clinic or developmental pediatrics clinic. The primary outcome was the proportion of patients with at least one psychotropic medication modification made 6-month posttesting that could be attributed to CYP2C19, CYP2D6, HLA-B*15:02, or HLA-A*31:01. Secondary outcomes included reason for testing, types of therapeutic modifications made, and whether the therapeutic modifications concorded with PGx guidelines. Results: A total of 193 patients were analyzed. The average age was 10 ± 4 years old, 60% were male, 78% were Caucasian. Sixty-eight percent had a primary diagnosis of a neurodevelopmental disorder, namely autism spectrum disorder (51%), and attention-deficit/hyperactivity disorder (14%). The reasons for PGx testing included medication inefficacy (34%), medication intolerance (20%), and family request (19%). At the time of PGx testing, 37% of patients were taking ≥1 psychotropic medication with PGx annotation. Overall, 35 PGx-related therapeutic modifications were made in 32 (17%) patients. These included continuing current PGx medication (6.2%) and starting PGx medication (5.2%). These modifications mainly involved antidepressants. Out of these 35 PGx-related therapeutic modifications, 94% were concordant with PGx guidelines. Among 29 patients who were prescribed at least one CYP2D6 inhibitor, 25 (86%) underwent CYP2D6 phenoconversion. Conclusions: It is critical to apply pediatric age-specific considerations when utilizing PGx testing in child and adolescent psychiatry. PGx testing stewardship could provide a framework to guide the clinical utility of PGx in a pediatric population with mental health conditions, including neurodevelopmental disorders.

Effects of pharmacist-driven protocol on naloxone prescribing rates in two primary care clinics.

The Centers for Disease Control and Prevention (CDC) Guidelines for Prescribing Opioids for Chronic Pain recommend co-prescribing naloxone as a harm reduction strategy when there is an increased risk of opioid overdose. Although naloxone co-prescribing is an important harm reduction strategy, many at risk patients are not prescribed naloxone. The objective was to assess the effectiveness of a pharmacist-driven protocol at increasing the number of patients co-prescribed naloxone according to CDC recommendations. The study design was a multi-center retrospective cohort to evaluate the outcomes of a quality improvement intervention at two primary care clinics which aimed to increase naloxone co-prescribing. The intervention used a two-pronged approach consisting of telephonic outreach to eligible patients by pharmacists and pharmacy interns related to naloxone education and recommendations for naloxone co-prescribing. Additionally, recommendations were sent to the primary care provider in the electronic medical record (EMR) for consideration and implementation. After the 3 month intervention, 57 of the 86 patients contacted were co-prescribed naloxone (66.3%). Most naloxone initiation occurred at the time of telephonic outreach as a new medication order (n = 36), however an additional 12 patients were co-prescribed naloxone at a subsequent primary care provider visit. The proportion of patients at each clinic with MME ≥ 50 co-prescribed naloxone significantly increased after implementation of the intervention (pre 25/64 vs. post 43/76, p = 0.043). Overall, telephonic outreach to patients with recommendations to primary care providers in the EMR were effective methods to increase the rate of naloxone co-prescribing in primary care based on this study.

Loss of Chondroitin Sulfate Modification Causes Inflammation and Neurodegeneration in skt Mice.

One major aspect of the aging process is the onset of chronic, low-grade inflammation that is highly associated with age-related diseases. The molecular mechanisms that regulate these processes have not been fully elucidated. We have identified a spontaneous mutant mouse line, small with kinky tail (skt), that exhibits accelerated aging and age-related disease phenotypes including increased inflammation in the brain and retina, enhanced age-dependent retinal abnormalities including photoreceptor cell degeneration, neurodegeneration in the hippocampus, and reduced lifespan. By positional cloning, we identified a deletion in chondroitin sulfate synthase 1 (Chsy1) that is responsible for these phenotypes in skt mice. CHSY1 is a member of the chondroitin N-acetylgalactosaminyltransferase family that plays critical roles in the biosynthesis of chondroitin sulfate, a glycosaminoglycan (GAG) that is attached to the core protein to form the chondroitin sulfate proteoglycan (CSPG). Consistent with this function, the Chsy1 mutation dramatically decreases chondroitin sulfate GAGs in the retina and hippocampus. In addition, macrophage and neutrophil populations appear significantly altered in the bone marrow and spleen of skt mice, suggesting an important role for CHSY1 in the functioning of these immune cell types. Thus, our study reveals a previously unidentified impact of CHSY1 in the retina and hippocampus. Specifically, chondroitin sulfate (CS) modification of proteins by CHSY1 appears critical for proper regulation of immune cells of the myeloid lineage and for maintaining the integrity of neuronal tissues, since a defect in this gene results in increased inflammation and abnormal phenotypes associated with age-related diseases.