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Importance: There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement., Objectives: To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug., Design, Setting, and Participants: This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022., Main Outcomes and Measures: PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs., Results: The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019., Conclusions and Relevance: In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.

Objective: Polypharmacy increases the risk of drug-drug interactions and adverse drug events. As obesity and rates of obesity-associated comorbid chronic conditions continue to rise, an improved understanding of whether children with obesity experience higher risk of polypharmacy is needed. This study aimed to compare chronic medication polypharmacy prevalence among children with and without a diagnosis of obesity., Methods: We performed a cross-sectional examination of prescription data for children aged 2-18 years prescribed ≥1 chronic medication using the 2019 Marketscan Medicaid database. Children with documented obesity were identified using medical visit diagnosis codes. Chronic medications included any ≥30-day prescription with ≥2 dispensed refills. Polypharmacy was defined as the prescription of ≥2 chronic medications for ≥1 overlapping days. Chi-squared tests compared polypharmacy prevalence and the distribution of chronic medication classes between children with and without obesity. Logistic regression determined the adjusted odds ratio (aOR) of polypharmacy for children with obesity, adjusting for relevant demographic and clinical differences., Results: Of 634,671 included children, 12.2% had documented obesity. More than one-half (52.7%) of children with obesity experienced polypharmacy compared with 47.6% of children without obesity (aOR 1.06 [95% confidence interval 1.04-1.08]). Chronic medication prescriptions, particularly for psychiatric and asthma medications, were more commonly prescribed among children with obesity than those without obesity., Conclusions: Children with documented obesity have higher polypharmacy prevalence than children without obesity. Clinicians must be aware of this risk and minimize inappropriate polypharmacy whenever possible. Future work should examine the consequences of polypharmacy, including drug-drug interactions and adverse drug events in children with obesity., (© 2022 Pharmacotherapy Publications, Inc.)

Background: Children with neurologic impairment (NI) are at risk for developing co-occurring chronic conditions, increasing their medical complexity and morbidity. We assessed the prevalence and timing of onset for those conditions in children with NI., Methods: This longitudinal analysis included 6229 children born in 2009 and continuously enrolled in Medicaid through 2015 with a diagnosis of NI by age 3 in the IBM Watson Medicaid MarketScan Database. NI was defined with an existing diagnostic code set encompassing neurologic, genetic, and metabolic conditions that result in substantial functional impairments requiring subspecialty medical care. The prevalence and timing of co-occurring chronic conditions was assessed with the Agency for Healthcare Research and Quality Chronic Condition Indicator system. Mean cumulative function was used to measure age trends in multimorbidity., Results: The most common type of NI was static (56.3%), with cerebral palsy (10.0%) being the most common NI diagnosis. Respiratory (86.5%) and digestive (49.4%) organ systems were most frequently affected by co-occurring chronic conditions. By ages 2, 4, and 6 years, the mean (95% confidence interval [CI]) numbers of co-occurring chronic conditions were 3.7 (95% CI 3.7-3.8), 4.6 (95% CI 4.5-4.7), and 5.1 (95% CI 5.1-5.2). An increasing percentage of children had ≥9 co-occurring chronic conditions as they aged: 5.3% by 2 years, 10.0% by 4 years, and 12.8% by 6 years., Conclusions: Children with NI enrolled in Medicaid have substantial multimorbidity that develops early in life. Increased attention to the timing and types of multimorbidity in children with NI may help optimize their preventive care and case management health services., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Background and Objectives: Although potentially dangerous, little is known about outpatient opioid exposure (OE) in children and youth with special health care needs (CYSHCN). We assessed the prevalence and types of OE and the diagnoses and health care encounters proximal to OE in CYSHCN., Methods: This is a retrospective cohort study of 2 597 987 CYSHCN aged 0-to-18 years from 11 states, continuously enrolled in Medicaid in 2016, with ≥1 chronic condition. OE included any filled prescription (single or multiple) for opioids. Health care encounters were assessed within 7 days before and 7 and 30 days after OE., Results: Among CYSHCN, 7.4% had OE. CYSHCN with OE versus without OE were older (ages 10-18 years: 69.4% vs 47.7%), had more chronic conditions (≥3 conditions: 49.1% vs 30.6%), and had more polypharmacy (≥5 other medication classes: 54.7% vs 31.2%), P < .001 for all. Most (76.7%) OEs were single fills with a median duration of 4 days (interquartile range: 3-6). The most common OEs were acetaminophen-hydrocodone (47.5%), acetaminophen-codeine (21.5%), and oxycodone (9.5%). Emergency department visits preceded 28.8% of OEs, followed by outpatient surgery (28.8%) and outpatient specialty care (19.1%). Most OEs were preceded by a diagnosis of infection (25.9%) or injury (22.3%). Only 35.1% and 62.2% of OEs were associated with follow-up visits within 7 and 30 days, respectively., Conclusions: OE in CYSHCN is common, especially with multiple chronic conditions and polypharmacy. In subsequent studies, researchers should examine the appropriateness of opioid prescribing, particularly in emergency departments, as well as assess for drug interactions with chronic medications and reasons for insufficient follow-up., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background and Objectives: Little is known about the use of chronic medications (CMs) in children. We assessed the prevalence of CM use in children and the association of clinical characteristics and health care resource use with the number of CMs used., Methods: This is a retrospective study of children ages 1 to 18 years using Medicaid from 10 states in 2014 grouped by the annual number of CMs (0, 1, 2-4, 5-9, and ≥10 medications), which are defined as a dispensed ≥30-day prescription with ≥2 dispensed refills. Trends in clinical characteristics and health care use by number of CMs were evaluated with the Cochran-Armitage trend test., Results: Of 4 594 061 subjects, 18.8% used CMs. CM use was 44.4% in children with a complex chronic condition. Across all children, the most common CM therapeutic class was neurologic (28.9%). Among CM users, 48.8% used multiple CMs (40.3% used 2-4, 7.0% used 5-9, and 0.5% used ≥10). The diversity of medications increased with increasing number of CMs: for 1 CM, amphetamine stimulants were most common (29.0%), and for ≥10 CMs, antiepileptics were most common (7.1%). Of $2.3 billion total pharmacy spending, 59.3% was attributable to children dispensed multiple CMs. Increased CM use (0 to ≥10 medications) was associated with increased emergency department use (32.1% to 56.2%) and hospitalization (2.3% to 36.7%)., Conclusions: Nearly 1 in 5 children with Medicaid used CMs. Use of multiple CMs was common and correlated with increased health care use. Understanding CM use in children should be fundamentally important to health care systems when strategizing how to provide safe, evidence-based, and cost-effective pharmaceutical care to children., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Child enrollment in Medicaid managed care (MMC) has expanded dramatically, primarily through state mandates. Care coordination is a key metric in MMC evaluation because it drives much of the proposed cost savings and may be associated with improved health outcomes and utilization. We evaluated the relationships between enrollment in 2 MMC structures, primary care case management (PCCM) and health maintenance organization (HMO) and access to and receipt of care coordination by children., Methods: Using data from the 2011/2012 National Survey of Children's Health and the Medicaid Statistical Information System state data mart, we conducted a retrospective, cross-sectional analysis of the relationships between fee-for-service, PCCM or HMO enrollment, and access to and receipt of care coordination. State-level univariate analyses and individual and state multilevel multivariable analyses evaluated correlations between MMC enrollment and care coordination, controlling for demographic characteristics and state financing levels., Results: In univariate and multilevel multivariable analyses, the PCCM penetration rate was significantly associated with increased access to care coordination (adjusted odds ratio: 1.23, P = .034) and receipt of care coordination (adjusted odds ratio: 1.37, P = .02). The HMO penetration rate was significantly associated with lower access to care coordination (adjusted odds ratio: 0.85, P = .05) and receipt of care coordination (adjusted odds ratio: 0.71, P < .001). Fee-for-service served as the referent., Conclusions: State utilization of MMC varied widely. These data suggest that care coordination may be more effective in PCCM than HMO structures. States should consider care coordination outcomes when structuring their Medicaid programs., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose. Dr Agrawal had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright © 2017 by the American Academy of Pediatrics.)

Background and Objectives: Outpatient pediatric polypharmacy is poorly characterized. Identification of at-risk populations has clinical implications for pharmacy case management programs. We described the degree of exposure to polypharmacy using parameters of depth (concurrent medication count) and duration, reported commonly dispensed medications and exposure to three example potential drug-drug interactions by different depths of polypharmacy, and determined patient characteristics associated with exposure to increased degrees (a function of depth and duration) of polypharmacy., Methods: Retrospective cohort study of Colorado fee-for-service Medicaid patients aged <18 years with 12 months of continuous enrollment. We calculated depth of polypharmacy using daily concurrent medication counts and duration of polypharmacy using days exposed to a certain depth. Multinomial logistic regression was used to assess patient characteristics associated with different degrees of polypharmacy., Results: Of 242 230 patients, 35% percent were exposed to any depth of polypharmacy, most commonly to anti-infective medications. Patients with higher depth polypharmacy were exposed to less common medications (psychotropic drugs, anticonvulsants, cardiovascular agents, and opioids) and to higher rates of exposure to potential drug-drug interactions. Of 47 972 patients exposed to ≥3 concurrent medications, 50% were exposed for <15 days, 25% for 15-38 days, 15% for 39-111 days, and 10% for 112-327 days. High-degree polypharmacy was associated with increasing age, male gender, and presence of a complex chronic condition., Conclusions: Outpatient pediatric polypharmacy occurs to a substantial degree for a small but vulnerable population of children, who may be candidates for pharmacy case management. We must determine whether increased exposure to high-degree polypharmacy causes harm., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: To examine the association between postdischarge outpatient follow-up and 30-day readmissions in Medicaid enrolled children with complex, chronic conditions., Study Design: This was a retrospective cohort analysis of Colorado Medicaid recipients with complex, chronic conditions who were discharged from the hospital between 2006 and 2008. The primary outcome was readmission between 4 and 30 days after index hospital discharge. Using multivariable logistic regression, we examined the association between early postdischarge outpatient visits (≤ 3 days postdischarge) and readmission. We secondarily analyzed the relationship between any outpatient visit from 4 to 29 days of index discharge and readmission., Results: For the 2415 patients with complex, chronic conditions included in the analysis, the 4- to 30-day readmission rate was 6.3%. The odds of readmission was significantly greater for patients with ≥ 1 outpatient visit ≤ 3 days after discharge compared with patients without a visit ≤ 3 days after discharge (aOR 1.7 [1.1-2.4]). The odds of readmission were significantly lower for patients with ≥ 1 outpatient visit from 4 to 29 days after discharge compared with patients without such visits (aOR 0.5 [0.3-0.7]). Other factors associated with readmission included index hospital length of stay and number of complex, chronic conditions., Conclusions: In medically complex children, there is a positive association between early postdischarge outpatient follow-up and readmission. There is an inverse association between later postdischarge outpatient follow-up and readmission. Outpatient follow-up occurring within 4-29 days after discharge may help to prevent 30-day readmissions. Additional research is needed to inform guidelines regarding longer term postdischarge outpatient follow-up in these children., (Copyright © 2015 Elsevier Inc. All rights reserved.)

ObjectiveTo examine how characteristics vary between children with any mental health (MH) diagnosis who have typical spending and the highest spending; to identify independent predictors of highest spending; and to examine drivers of spending groups.MethodsThis retrospective analysis utilized 2016 Medicaid claims from 11 states and included 775,945 children ages 3 to 17 years with any MH diagnosis and at least 11 months of continuous coverage. We compared demographic characteristics and Medicaid expenditures based on total health care spending: the top 1% (highest-spending) and remaining 99% (typical-spending). We used chi-squared tests to compare the 2 groups and adjusted logistic regression to identify independent predictors of being in the top 1% highest-spending group.ResultsChildren with MH conditions accounted for 55% of Medicaid spending among 3- to 17-year olds. Patients in the highest-spending group were more likely to be older, have multiple MH conditions, and have complex chronic physical health conditions (P

BACKGROUND AND OBJECTIVES: Drug--drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. METHODS: We performed a cross-sectional study of children aged 0 to 18 years with $1 ambulatory encounter, and $2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database. DDIs (exposure to a major DDI for $1 day) and the adverse physiologic effects of each DDI were identified using DrugBank's interaction database. Primary outcomes included the prevalence and rate of major DDI exposure. We used logistic regression to assess patient characteristics associated with DDI exposure. We examined the rate of DDI exposures per 100 children by adverse physiologic effects category, and organ-level effects (eg, heart rate-corrected QT interval prolongation). RESULTS: Of 781 019 children with $2 medication exposures, 21.4% experienced $1 major DDI exposure. The odds of DDI exposure increased with age and with medical and mental health complexity. Frequently implicated drugs included: Clonidine, psychiatric medications, and asthma medications. The highest adverse physiologic effect exposure rate per 100 children included: Increased drug concentrations (14.6), central nervous system depression (13.6), and heart rate-corrected QT interval prolongation (9.9). CONCLUSIONS: One in 5 Medicaid-insured children with $2 prescription medications were exposed to major DDIs annually, with higher exposures in those with medical or mental health complexity. DDI exposure places children at risk for negative health outcomes and adverse drug events, especially in the harder-to-monitor outpatient setting. [ABSTRACT FROM AUTHOR]