A Mixed-Methods Protocol to Identify Best Practices for Implementing Pharmacogenetic Testing in Clinical Settings.

Using a patient's genetic information to inform medication prescriptions can be clinically effective; however, the practice has not been widely implemented. Health systems need guidance on how to engage with providers to improve pharmacogenetic test utilization. Approaches from the field of implementation science may shed light on the complex factors affecting pharmacogenetic test use in real-world settings and areas to target to improve utilization. This paper presents an approach to studying the application of precision medicine that utilizes mixed qualitative and quantitative methods and implementation science frameworks to understand which factors or combinations consistently account for high versus low utilization of pharmocogenetic testing. This approach involves two phases: (1) collection of qualitative and quantitative data from providers-the cases-at four clinical institutions about their experiences with, and utilization of, pharmacogenetic testing to identify salient factors; and (2) analysis using a Configurational Comparative Method (CCM), using a mathematical algorithm to identify the minimally necessary and sufficient factors that distinguish providers who have higher utilization from those with low utilization. Advantages of this approach are that it can be used for small to moderate sample sizes, and it accounts for conditions found in real-world settings by demonstrating how they coincide to affect utilization.

North Carolina's multi-institutional pharmacogenomics efforts with the North Carolina Precision Health Collaborative.

The North Carolina Precision Health Collaborative is an interdisciplinary, public-private consortium of precision health experts who strategically align statewide resources and strengths to elevate precision health in the state and beyond. Pharmacogenomics (PGx) is a key area of focus for the North Carolina Precision Health Collaborative. Experts from Atrium Health's Levine Cancer Institute, Duke University/Duke Health System, Mission Health and the University of North Carolina (UNC) at Chapel Hill/UNC Health System have collaborated since 2017 to implement strategic PGx initiatives, including basic sciences research, translational research and clinical implementation of germline testing into practice and policy. This institutional profile highlights major PGx programs and initiatives across these organizations and how the collaborative is working together to advance PGx science and implementation.

Evaluation of the Financial and Health Burden of Infants at Risk for Respiratory Syncytial Virus.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading viral cause of death in infants younger than 1 year. In July 2014, the American Academy of Pediatrics (AAP) Committee on Infectious Diseases concluded that the "limited clinical benefit" for infants born at more than 29 weeks' gestation, together with the associated high cost of the immunoprophylaxis, no longer supported the routine use of palivizumab (Synagis). PURPOSE: To evaluate the impact of the newly adopted AAP palivizumab prophylaxis administration on health and subsequent hospital costs of infants born between 29 and less than 32 weeks' gestation. METHODS: A retrospective cohort analysis from a single institution across the duration of the study comparing the clinical and financial outcomes of infants (aged < 32 weeks) treated under the 2009 AAP guidelines (PRE) and infants (aged >29 weeks) managed after the 2014 AAP guidelines (POST) took effect. RESULTS: RSV-positive admissions were greater in the POST cohort versus the PRE cohort (P = .04). There were no readmission deaths due to RSV infection in either cohort. The number needed to treat to avoid a single RSV-positive hospitalization was 20 infants at an estimated palivizumab cost of $90,000 to avoid an estimated hospital cost of $29,000. IMPLICATIONS FOR PRACTICE: Assessment of individual risk factors and their ability to predict severe RSV risk/disease, thus, would allow providers greater flexibility in determining need for prophylaxis therapy. IMPLICATIONS FOR RESEARCH: Longitudinal evaluation of financial and clinical outcomes is needed to determine the impact of the 2014 AAP revised regulatory guidelines.

Ferumoxytol use as an intravenous contrast agent for magnetic resonance angiography.

OBJECTIVE: To evaluate the efficacy and safety of ferumoxytol for use in magnetic resonance angiography (MRA) of the vasculature. DATA SOURCES: Literature was accessed through MEDLINE (1946-September 2011) and EMBASE (1947-September 2011) using the terms ferumoxytol, magnetic resonance imaging and angiography, blood pool agent, and superparamagnetic iron oxide. Reference citations from identified publications were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and human studies (N = 9) were identified that evaluated ferumoxytol use in magnetic resonance imaging (MRI). Articles that evaluated the use of the drug in first-pass and equilibrium phase imaging of the vasculature were included (n = 4). DATA SYNTHESIS: Contrast agents for MRI improve disease characterization and diagnosis. Ferumoxytol, a medication approved for treatment of iron deficiency anemia in adults with chronic kidney disease, has superparamagnetic properties. As a blood pool agent, ferumoxytol remains primarily in the intravascular space. Therefore, its use in MRI may increase image sensitivity and specificity and have a decreased adverse effect profile compared to other contrast agents. Specifically, ferumoxytol may be an option for MRA, a specific type of MRI that images blood vessels. In the 4 studies evaluated here, ferumoxytol was administered primarily to healthy adults as an accumulative dose of 4 mg Fe/kg injected at 1 mL/sec. Not all studies reported adverse events and addressed safety monitoring. The evaluated studies are limited by small size, open-label design, and noncomparative methodology. CONCLUSIONS: Data from small pilot studies suggest that ferumoxytol may improve image quality in MRA; however, further investigation is necessary to establish its efficacy and safety. Large randomized, active-comparator trials are needed to establish optimal dosing, imaging procedures, and safety monitoring.

Characteristics of ambulatory anticoagulant adverse drug events: a descriptive study.

BACKGROUND: Despite the high frequency with which adverse drug events (ADEs) occur in outpatient settings, detailed information regarding these events remains limited. Anticoagulant drugs are associated with increased safety concerns and are commonly involved in outpatient ADEs. We therefore sought to evaluate ambulatory anticoagulation ADEs and the patient population in which they occurred within the Duke University Health System (Durham, NC, USA). METHODS: A retrospective chart review of ambulatory warfarin-related ADEs was conducted. An automated trigger surveillance system identified eligible events in ambulatory patients admitted with an International Normalized Ratio (INR) >3 and administration of vitamin K. Event and patient characteristics were evaluated, and quality/process improvement strategies for ambulatory anticoagulation management are described. RESULTS: A total of 169 events in 167 patients were identified from December 1, 2006-June 30, 2008 and included in the study. A median supratherapeutic INR of 6.1 was noted, and roughly half of all events (52.1%) were associated with a bleed. Nearly 74% of events resulted in a need for fresh frozen plasma; 64.8% of bleeds were classified as major. A total of 59.2% of events were at least partially responsible for hospital admission. Median patient age was 68 y (range 36-95 y) with 24.9% initiating therapy within 3 months prior to the event. Of events with a prior documented patient visit (n = 157), 73.2% were seen at a Duke clinic or hospital within the previous month. Almost 80% of these patients had anticoagulation therapy addressed, but only 60.0% had a follow-up plan documented in the electronic note. CONCLUSIONS: Ambulatory warfarin-related ADEs have significant patient and healthcare utilization consequences in the form of bleeding events and associated hospital admissions. Recommendations for improvement in anticoagulation management include use of information technology to assist monitoring and follow-up documentation, avoid drug interactions, and engage patients in their care.

Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder.

OBJECTIVE: To evaluate the efficacy and safety of melatonin for the treatment of insomnia in pediatric patients with attention-deficit/hyperactivity disorder (ADHD). DATA SOURCES: Literature was accessed through MEDLINE (1948-August 2009), EMBASE (1950-August 2009), and Scopus (1960-August 2009) using the terms melatonin, attention-deficit/hyperactivity disorder (ADHD), pediatric, insomnia, sleep disorder, and sleep. In addition, reference citations from publications identified were reviewed for relevant information. STUDY SELECTION AND DATA EXTRACTION: All English-language articles and human studies were identified and evaluated. Results from all identified randomized trials (n = 5), safety studies (n = 1), long-term follow-up studies (n = 1), post hoc retrospective analyses (n = 1), meta-analyses (n = 2), review articles (n = 9), and letters (n = 1) were summarized. DATA SYNTHESIS: Pediatric insomnia is prevalent in children with ADHD and impacts academic performance, social functioning, overall health, and family life. First-line therapy includes ruling out differential diagnoses, optimizing ADHD stimulant treatment, and initiating good sleep hygiene and behavioral therapy. Adjuvant pharmacotherapy is then an option and melatonin is often prescribed. Melatonin regulates circadian rhythm sleep disorders such as sleep-onset insomnia (SOI) in children with ADHD. Four studies in children with ADHD and insomnia showed improvement in sleep onset and sleep latency. Studies included children 6-14 years old and melatonin doses ranged from 3 to 6 mg administered within a few hours of a scheduled bedtime. In all studies, adverse events were transient and mild. The available melatonin studies are limited by small size and short duration; variable SOI criteria, ADHD criteria, and treatment assessments; and lack of generalizability. CONCLUSIONS: Available data suggest that melatonin is a well-tolerated and efficacious treatment option for pediatric patients with chronic SOI and ADHD. Regulated melatonin products and larger, well-designed trials to establish optimal dosing regimens and long-term safety are needed.