Barriers to Buprenorphine Dispensing by Medicaid-Participating Community Retail Pharmacies.

Importance: Controlled substances have regulatory requirements under the US Federal Controlled Substance Act that must be met before pharmacies can stock and dispense them. However, emerging evidence suggests there are pharmacy-level barriers in access to buprenorphine for treatment for opioid use disorder even among pharmacies that dispense other opioids. Objective: To estimate the proportion of Medicaid-participating community retail pharmacies that dispense buprenorphine, out of Medicaid-participating community retail pharmacies that dispense other opioids and assess if the proportion dispensing buprenorphine varies by Medicaid patient volume or rural-urban location. Design, Setting, and Participants: This serial cross-sectional study included Medicaid pharmacy claims (2016-2019) data from 6 states (Kentucky, Maine, North Carolina, Pennsylvania, Virginia, West Virginia) participating in the Medicaid Outcomes Distributed Research Network (MODRN). Community retail pharmacies serving Medicaid-enrolled patients were included, mail-order pharmacies were excluded. Analyses were conducted from September 2022 to August 2023. Main Outcomes and Measures: The proportion of pharmacies dispensing buprenorphine approved for opioid use disorder among pharmacies dispensing an opioid analgesic or buprenorphine prescription to at least 1 Medicaid enrollee in each state. Pharmacies were categorized by median Medicaid patient volume (by state and year) and rurality (urban vs rural location according to zip code). Results: In 2016, 72.0% (95% CI, 70.9%-73.0%) of the 7038 pharmacies that dispensed opioids also dispensed buprenorphine to Medicaid enrollees, increasing to 80.4% (95% CI, 79.5%-81.3%) of 7437 pharmacies in 2019. States varied in the percent of pharmacies dispensing buprenorphine in Medicaid (range, 73.8%-96.4%), with significant differences between several states found in 2019 (χ2 P < .05), when states were most similar in the percent of pharmacies dispensing buprenorphine. A lower percent of pharmacies with Medicaid patient volume below the median dispensed buprenorphine (69.1% vs 91.7% in 2019), compared with pharmacies with above-median patient volume (χ2 P < .001). Conclusions and Relevance: In this serial cross-sectional study of Medicaid-participating pharmacies, buprenorphine was not accessible in up to 20% of community retail pharmacies, presenting pharmacy-level barriers to patients with Medicaid seeking buprenorphine treatment. That some pharmacies dispensed opioid analgesics but not buprenorphine suggests that factors other than compliance with the Controlled Substance Act influence pharmacy dispensing decisions.

Inflammatory Bowel Disease in Appalachian Kentucky: An Investigation of Outcomes and Health Care Utilization.

BACKGROUND: Rural residence has been associated with a lower incidence of inflammatory bowel disease (IBD) but higher health care utilization and worse outcomes. Socioeconomic status is intrinsically tied to both IBD incidence and outcomes. Inflammatory bowel disease outcomes have not been investigated in Appalachia: a rural, economically distressed region rife with risk factors for both increased incidence and unfavorable outcomes. METHODS: Hospital inpatient discharge and outpatient services databases were utilized to assess outcomes in patients diagnosed with either Crohn's disease (CD) or ulcerative colitis (UC) in Kentucky. Encounters were classified by patient residence in Appalachian or non-Appalachian counties. Data were reported as crude and age-adjusted rates of visits per 100,000 population per year collected in 2016 to 2019. National inpatient discharge data from 2019, stratified by rural and urban classification codes, were utilized to compare Kentucky to national trends. RESULTS: Crude and age-adjusted rates of inpatient, emergency department and outpatient encounters were higher in the Appalachian cohort for all 4 years observed. Appalachian inpatient encounters are more frequently associated with a surgical procedure (Appalachian, 676, 24.7% vs non-Appalachian, 1408, 22.2%; P = .0091). In 2019, the Kentucky Appalachian cohort had significantly higher crude and age-adjusted rates of inpatient discharges for all IBD diagnoses compared with national rural and nonrural populations (crude 55.2; 95% CI, 50.9-59.5; age-adjusted 56.7; 95% CI, 52.1-61.3). CONCLUSIONS: There is disproportionately higher IBD health care utilization in Appalachian Kentucky compared with all cohorts, including the national rural population. There is a need for aggressive investigation into root causes of these disparate outcomes and identification of barriers to appropriate IBD care.

The Kentucky Appalachian IBD population experiences increased health care utilization, with increased rates of inpatient admissions, emergency department, and outpatient visits compared with non-Appalachian Kentuckians. Kentucky Appalachian rates of inpatient admissions are higher compared with national rates, controlling for rural residence.

Telemedicine Buprenorphine Initiation and Retention in Opioid Use Disorder Treatment for Medicaid Enrollees.

Importance: Early COVID-19 mitigation strategies placed an additional burden on individuals seeking care for opioid use disorder (OUD). Telemedicine provided a way to initiate and maintain transmucosal buprenorphine treatment of OUD. Objective: To examine associations between transmucosal buprenorphine OUD treatment modality (telemedicine vs traditional) during the COVID-19 public health emergency and the health outcomes of treatment retention and opioid-related nonfatal overdose. Design, Setting, and Participants: This retrospective cohort study was conducted using Medicaid claims and enrollment data from November 1, 2019, to December 31, 2020, for individuals aged 18 to 64 years from Kentucky and Ohio. Data were collected and analyzed in June 2022, with data updated during revision in August 2023. Exposures: The primary exposure of interest was the modality of the transmucosal buprenorphine OUD treatment initiation. Relevant patient demographic and comorbidity characteristics were included in regression models. Main Outcomes and Measures: There were 2 main outcomes of interest: retention in treatment after initiation and opioid-related nonfatal overdose after initiation. For outcomes measured after initiation, a 90-day follow-up period was used. The main analysis used a new-user study design; transmucosal buprenorphine OUD treatment initiation was defined as initiation after more than a 60-day gap in buprenorphine treatment. In addition, uptake of telemedicine for buprenorphine was examined, overall and within patients initiating treatment, across quarters in 2020. Results: This study included 41 266 individuals in Kentucky (21 269 women [51.5%]; mean [SD] age, 37.9 [9.0] years) and 50 648 individuals in Ohio (26 425 women [52.2%]; mean [SD] age, 37.1 [9.3] years) who received buprenorphine in 2020, with 18 250 and 24 741 people initiating buprenorphine in Kentucky and Ohio, respectively. Telemedicine buprenorphine initiations increased sharply at the beginning of 2020. Compared with nontelemedicine initiation, telemedicine initiation was associated with better odds of 90-day retention with buprenorphine in both states (Kentucky: adjusted odds ratio, 1.13 [95% CI, 1.01-1.27]; Ohio: adjusted odds ratio, 1.19 [95% CI, 1.06-1.32]) in a regression analysis adjusting for patient demographic and comorbidity characteristics. Telemedicine initiation was not associated with opioid-related nonfatal overdose (Kentucky: adjusted odds ratio, 0.89 [95% CI, 0.56-1.40]; Ohio: adjusted odds ratio, 1.08 [95% CI, 0.83-1.41]). Conclusions and Relevance: In this cohort study of Medicaid enrollees receiving buprenorphine for OUD, telemedicine buprenorphine initiation was associated with retention in treatment early during the COVID-19 pandemic. These findings add to the literature demonstrating positive outcomes associated with the use of telemedicine for treatment of OUD.

Prenatal syphilis screening among pregnant Medicaid enrollees by sexually transmitted infection history as well as race and ethnicity.

BACKGROUND: Congenital syphilis can cause severe morbidity, including miscarriage and stillbirth, and rates are increasing rapidly within the United States. However, congenital syphilis can be prevented with early detection and treatment of syphilis during pregnancy. Current screening recommendations propose that all women should be screened early in pregnancy, whereas women with elevated risks for congenital syphilis should be screened again later in pregnancy. The rapid increase in congenital syphilis rates suggests that there are still gaps in prenatal syphilis screening. OBJECTIVE: This study aimed to examine associations between the odds of prenatal syphilis screening and sexually transmitted infection history or other patient characteristics across 3 states with elevated rates of congenital syphilis. STUDY DESIGN: We used the Medicaid claims data from Kentucky, Louisiana, and South Carolina for women with deliveries between 2017 and 2021. Within each state, we examined the log-odds of prenatal syphilis screening as a function of the mother's health history, demographic factors, and Medicaid enrollment history. Patient history was established using a 4-year lookback period of the Medicaid claims data; in state A, sexually transmitted infection surveillance data were used to improve the sexually transmitted infection history. RESULTS: The prenatal syphilis screening rates varied by state, ranging from 62.8% to 85.1% of deliveries to women without a recent history of sexually transmitted infections and from 78.1% to 91.1% of deliveries to women with a previous sexually transmitted infection. For the main outcome of syphilis screening at any time during pregnancy, deliveries associated with previous sexually transmitted infections had 1.09 to 1.37 times higher adjusted odds ratios of undergoing screening. Deliveries to women with continuous Medicaid coverage throughout the first trimester also had higher odds of syphilis screening at any time (adjusted odds ratio, 2.45-3.15). Among deliveries to women with a previous sexually transmitted infection, only 53.6% to 63.6% underwent first-trimester screening and this rate was still just 55.0% to 69.5% when considering only deliveries to women with a previous sexually transmitted infection and full first-trimester Medicaid coverage. Fewer delivering women underwent third-trimester screening (20.3%-55.8% of women with previous sexually transmitted infection). Compared with deliveries to White women, deliveries to Black women had lower odds of first-trimester screening (adjusted odds ratio, 0.85 in all states) but higher odds of third-trimester screening (adjusted odds ratio, 1.23-2.03), potentially impacting maternal and birth outcomes. For state A, linkage to surveillance data doubled the rate of detection of a previous sexually transmitted infection because 53.0% of deliveries by women with a previous sexually transmitted infection would not have had sexually transmitted infection history detected using Medicaid claims alone. CONCLUSION: A previous sexually transmitted infection and continuous preconception Medicaid enrollment were associated with higher rates of syphilis screening, but Medicaid claims alone do not fully capture the sexually transmitted infection history of patients. The overall screening rates were lower than would be expected given that all women should undergo prenatal screening, but the rates in the third trimester were particularly low. Of note, there are gaps in early screening for non-Hispanic Black women who had lower odds of first-trimester screening when compared with non-Hispanic White women despite being at elevated risk for syphilis.

The policy landscape for naloxone distribution in four states highly impacted by fatal opioid overdoses.

Background: Expanding access to naloxone is one of the most impactful interventions in decreasing opioid-related mortality. However, state distribution rates of naloxone are insufficient to meet community need. The current study sought to better understand this gap by focusing on state policies that may facilitate or impede naloxone distribution in four states highly impacted by fatal opioid overdoses - Kentucky, Massachusetts, New York, and Ohio. Methods: We provide a descriptive analysis of the policy landscape impacting naloxone distribution through pharmacy and community channels in the four states participating in the HEALing Communities Study (HCS). Publicly available data and the expertise of the research team were used to describe each state's naloxone access laws (NALs), Medicaid coverage of naloxone, and community overdose education and naloxone distribution infrastructure. Data presented in this study represent the most current policy landscape through September 2022. Results: Variation exists between specific components of the NALs of each state, the structure of Medicaid coverage of naloxone, and the community distribution infrastructure networks. Massachusetts and New York have a statewide standing order, but other states use different strategies short of a statewide standing order to expand access to naloxone. Quantity limits specific to naloxone may limit access to Medicaid beneficiaries in some states. Conclusion: States participating in the HCS have developed innovative but different mechanisms to ensure naloxone access. Policies were dynamic and moved towards greater access. Research should consider the policy landscape in the implementation and sustainability of interventions as well as the analysis of outcomes.

The Impact of Naloxone Coprescribing Mandates on Opioid-Involved Overdose Deaths.

INTRODUCTION: Since 2017, a total of 10 states have mandated naloxone coprescribing intended to prevent fatal opioid overdoses. This study aims to assess the association between naloxone coprescribing/offering mandates and opioid-involved overdose deaths on the basis of the opioid type. METHODS: Data on overdose deaths from 1999 to 2020 came from the National Center for Health Statistics CDC WONDER Online Database. This study examined deaths stratified by illicit/synthetic opioids and prescription/treatment opioids. Difference-in-difference negative binomial regression models estimated average marginal effects and 95% CIs. Covariates included opioid dispensing rate, Good Samaritan law, pharmacy-based naloxone access law, mandatory use of prescription drug monitoring program, and recreational cannabis dispensaries. Data collection and analysis were conducted in 2022. RESULTS: Ten states implemented naloxone coprescribing/offering mandates during the period. Coprescribing/offering mandates significantly reduced the number of prescription/treatment overdose deaths by 8.61 per state per quarter (95% CI= -15.13, -2.09), a 16% reduction from the counterfactual estimates. Coprescribing/offering mandates did not significantly impact illicit/synthetic overdose deaths (average marginal effect=0.32; 95% CI= -18.27, 18.91). CONCLUSIONS: Coprescribing/offering mandates prevent overdose deaths for its target population, individuals using prescription/treatment opioids. These mandates do not appear to impact populations using illicit/synthetic opioids; thus, expanded efforts are needed to reach these individuals.

Medicaid expansion and access to naloxone in metropolitan and nonmetropolitan areas.

PURPOSE: The opioid crisis remains a major public health concern in the United States. Naloxone is used to reverse opioid overdoses. This study examined Medicaid expansion on naloxone prescriptions in retail pharmacies in metropolitan (metro) and nonmetropolitan (nonmetro) areas (2011-2017). METHODS: We used population average models to evaluate the association of Medicaid expansion at the state level on the number of naloxone prescriptions dispensed and the percentage paid by Medicaid, including adjustment for opioid-related and state-level policy covariates. Difference-in-difference modeling was performed as a sensitivity analysis. FINDINGS: States that expanded Medicaid had higher unadjusted naloxone dispensing rates and Medicaid-paid percentage of naloxone in metro and nonmetro areas. Medicaid expansion was not associated with the number of naloxone dispensed in either metro (adjusted rate ratio (ARR) = 1.26, 95% CI: [0.80, 1.97]) or nonmetro (ARR = 0.67, 95% CI: [0.37, 1.19]) areas after covariate adjustment. In metro areas, Medicaid expansion was associated with a significant increase of 3.86 percentage points (95% CI: [0.09, 7.63]) in the Medicaid-paid percentage of naloxone dispensing compared to nonexpansion states, but this association was not significant in nonmetro areas. There was also a significant time by Medicaid expansion interaction on the Medicaid-paid percentage of naloxone dispensed (metro: estimate = 0.74, 95% CI: [0.36, 1.12]; nonmetro: estimate = 0.68, 95% CI: [0.17, 1.18]). CONCLUSIONS: Medicaid expansion increased naloxone access by increasing the Medicaid-paid percentage of naloxone prescriptions in metro areas. States with Medicaid expansion had a faster rate of increase in the Medicaid-paid percentage of naloxone than states without Medicaid expansion in nonmetro areas.

Enhancing research data infrastructure to address the opioid epidemic: the Opioid Overdose Network (O2-Net).

Opioid Overdose Network is an effort to generalize and adapt an existing research data network, the Accrual to Clinical Trials (ACT) Network, to support design of trials for survivors of opioid overdoses presenting to emergency departments (ED). Four institutions (Medical University of South Carolina [MUSC], Dartmouth Medical School [DMS], University of Kentucky [UK], and University of California San Diego [UCSD]) worked to adapt the ACT network. The approach that was taken to enhance the ACT network focused on 4 activities: cloning and extending the ACT infrastructure, developing an e-phenotype and corresponding registry, developing portable natural language processing tools to enhance data capture, and developing automated documentation templates to enhance extended data capture. Overall, initial results suggest that tailoring of existing multipurpose federated research networks to specific tasks is feasible; however, substantial efforts are required for coordination of the subnetwork and development of new tools for extension of available data. The initial output of the project was a new approach to decision support for the prescription of naloxone for home use in the ED, which is under further study within the network.

Trends in Urine Drug Monitoring Among Persons Receiving Long-Term Opioids and Persons with Opioid Use Disorder in the United States.

BACKGROUND: Practice guidelines recommend urine drug monitoring (UDM) at least annually in the setting of chronic opioid therapy as an objective assessment of substance use. However, empirical evidence on who gets tested and how often testing occurs is lacking. OBJECTIVES: This study investigates 10-year UDM trends in the United States based on 2 factors: (1) the duration of prescription opioid treatment, and (2) having an opioid use disorder (OUD) diagnosis and medications for opioid use disorder (MOUD) prescriptions. STUDY DESIGN: Observational cross-sectional study. SETTING: Research was conducted using administrative claims data from Optum's deidentified Clinformatics Data Mart Database for the period 2007 to 2016. The dataset contained information on the plan enrollment and health care claims from 50 states and the District of Columbia. METHODS: To examine trends in UDM based on the duration of prescription opioid treatment, persons receiving prescription opioid analgesics were categorized into 4 groups based on the number of days covered: (a) less than 90 days, (b) 90 to 179 days, (c) 180 to 269 days, and (d) at least 270 days. To examine trends based on an OUD diagnosis and MOUD prescriptions, persons diagnosed with OUD were identified and categorized based on the presence of MOUD prescriptions as follows: (a) OUD with buprenorphine (BPN) and naltrexone (NTX) in the same year; (b) OUD with BPN only; (c) OUD with NTX only; (d) OUD with chronic prescription opioid analgesics (>= 90 days); (e) OUD without prescription opioid analgesics, BPN, or NTX; and (f) chronic prescription opioid analgesics (>= 90 days) without an OUD diagnosis. For analysis, the percent receiving UDM was estimated per group per year. Then the data were restricted to those receiving at least one UDM to estimate the average number of UDM per person. RESULTS: Data included an average of 364,485 persons per year receiving prescription opioid analgesics for chronic use, and 10,277 per year receiving an OUD diagnosis. Among those receiving prescription opioid analgesics, less than 50% received UDM. For those receiving at least one UDM, one additional UDM was performed per person as the duration of opioids increased by 90 days. Among persons with OUD, the percent receiving UDM was the highest for those receiving both BPN and NTX (87%), followed by those receiving BPN only (80%), chronic opioids (79%), NTX only (72%), and those not receiving any MOUD/opioids (54%). LIMITATIONS: Methadone dispensing for OUD treatments was not captured in administrative claims data. CONCLUSIONS: Although recommended for patients with chronic pain, UDM is provided less than half of the time for these patients. However, once patients received at least one UDM, they would continue to receive it on a fairly regular basis. Compared with those with chronic pain, persons diagnosed with OUD are more likely to receive UDM at a more frequent interval.

The impact of medical and recreational marijuana laws on opioid prescribing in employer-sponsored health insurance.

Using data from Truven Health MarketScan Commercial Claims and Encounters Database between 2009 and 2015, we studied the effects of medical and recreational marijuana laws on opioid prescribing in employer-sponsored health insurance. We used a differences-in-differences (DD) approach and found that the implementation of medical marijuana laws (MMLs) and recreational marijuana laws (RMLs) reduced morphine milligram equivalents per enrollee by 7% and 13%, respectively. The reduction associated with MMLs was predominately in people aged 55-64, whereas the reduction associated with RMLs was largely in people aged 35-44 and aged 45-54. Our findings suggest that both MMLs and RMLs have the potential to reduce opioid prescribing in the privately insured population, especially for the middle-aged population.

Using medical claims database to develop a population disease progression model for leuprorelin-treated subjects with hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is a widely used treatment for patients with hormone-sensitive prostate cancer (PCa). However, duration of treatment response varies, and most patients eventually experience disease progression despite treatment. Leuprorelin is a luteinizing hormone-releasing hormone (LHRH) agonist, a commonly used form of ADT. Prostate-specific antigen (PSA) is a biomarker for monitoring disease progression and predicting treatment response and survival in PCa. However, time-dependent profile of tumor regression and growth in patients with hormone-sensitive PCa on ADT has never been fully characterized. In this analysis, nationwide medical claims database provided by Humana from 2007 to 2011 was used to construct a population-based disease progression model for patients with hormone-sensitive PCa on leuprorelin. Data were analyzed by nonlinear mixed effects modeling utilizing Monte Carlo Parametric Expectation Maximization (MCPEM) method in NONMEM. Covariate selection was performed using a modified Wald's approximation method with backward elimination (WAM-BE) proposed by our group. 1113 PSA observations from 264 subjects with malignant PCa were used for model development. PSA kinetics were well described by the final covariate model. Model parameters were well estimated, but large between-patient variability was observed. Hemoglobin significantly affected proportion of drug-resistant cells in the original tumor, while baseline PSA and antiandrogen use significantly affected treatment effect on drug-sensitive PCa cells (Ds). Population estimate of Ds was 3.78 x 10-2 day-1. Population estimates of growth rates for drug-sensitive (Gs) and drug-resistant PCa cells (GR) were 1.96 x 10-3 and 6.54 x 10-4 day-1, corresponding to a PSA doubling time of 354 and 1060 days, respectively. Proportion of the original PCa cells inherently resistant to treatment was estimated to be 1.94%. Application of population-based disease progression model to clinical data allowed characterization of tumor resistant patterns and growth/regression rates that enhances our understanding of how PCa responds to ADT.

Association between state Medicaid expansion status and naloxone prescription dispensing.

OBJECTIVE: To test whether Medicaid expansion is associated with (a) a greater number of naloxone prescriptions dispensed and (b) a higher proportion of naloxone prescriptions paid by Medicaid. DATA SOURCES/STUDY SETTING: We used the IQVIA National Prescription Audit to obtain data on per state per quarter naloxone prescription dispensing for the period 2011-16. STUDY DESIGN: In this quasi-experimental design study, the impact of Medicaid expansion on naloxone prescription dispensing was examined using difference-in-difference estimation models. State-level covariates including pharmacy-based naloxone laws (standing/protocol orders and direct authority to dispense naloxone), third-party prescribing laws, opioid analgesic prescribing rates, opioid-involved overdose death rates, and population size were controlled for in the analysis. PRINCIPAL FINDINGS: Medicaid expansion was associated with 38 additional naloxone prescriptions dispensed per state per quarter compared to nonexpansion controls, on average (P = .030). Also, Medicaid expansion resulted in an average increase of 9.86 percent in the share of naloxone prescriptions paid by Medicaid per state per quarter (P < .001). CONCLUSIONS: Our study found that Medicaid expansion increased naloxone availability. This finding suggests that it will be important to consider naloxone access when making federal- and state-level decisions affecting Medicaid coverage.

Integrating data science into the translational science research spectrum: A substance use disorder case study.

The availability of large healthcare datasets offers the opportunity for researchers to navigate the traditional clinical and translational science research stages in a nonlinear manner. In particular, data scientists can harness the power of large healthcare datasets to bridge from preclinical discoveries (T0) directly to assessing population-level health impact (T4). A successful bridge from T0 to T4 does not bypass the other stages entirely; rather, effective team science makes a direct progression from T0 to T4 impactful by incorporating the perspectives of researchers from every stage of the clinical and translational science research spectrum. In this exemplar, we demonstrate how effective team science overcame challenges and, ultimately, ensured success when a diverse team of researchers worked together, using healthcare big data to test population-level substance use disorder (SUD) hypotheses generated from preclinical rodent studies. This project, called Advancing Substance use disorder Knowledge using Big Data (ASK Big Data), highlights the critical roles that data science expertise and effective team science play in quickly translating preclinical research into public health impact.

Neonatal Abstinence Syndrome and Childhood Mental Health Conditions, 2009-2015: Commercial Versus Medicaid Populations.

OBJECTIVE: This study aimed to examine mental health conditions of children diagnosed with neonatal abstinence syndrome (NAS) in a commercially insured population and compare them with a multistate Medicaid-insured population identified in prior research. METHODS: Data from the IBM MarketScan Commercial Database from January 1, 2009, to September 30, 2015, were used to identify mental health conditions among children ages 1-5 both with and without NAS. Frequency analyses were conducted to ascertain intrapopulation differences and differences between the commercially insured and Medicaid populations. RESULTS: The NAS rate in the Medicaid population was 28.7 times higher than in the commercially insured population. Although the sample of children with NAS was small, and the results must be interpreted with caution, elevated rates of childhood mental health conditions observed in the commercially insured population were comparable to the Medicaid population. CONCLUSIONS: This analysis emphasizes the difference in rates of NAS between commercially insured and Medicaid populations.

Association of Naloxone Coprescription Laws With Naloxone Prescription Dispensing in the United States.

Importance: To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients. Objective: To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies. Design, Setting, and Participants: This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA's national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month and the study period was January 1, 2011, to December 31, 2017. Exposures: State legal intervention mandating naloxone coprescription. Main Outcomes and Measures: Number of naloxone prescriptions dispensed. State rates of naloxone prescriptions dispensed per month per 100 000 standard population were calculated. Results: The rate of naloxone dispensing increased after implementation of legal mandates for naloxone coprescription. An estimated 88 naloxone prescriptions per 100 000 were dispensed in Virginia and 111 prescriptions per 100 000 were dispensed in Vermont during the first full month the legal requirement was effective. In comparison, 16 naloxone prescriptions per 100 000 were dispensed in the 10 states (including the District of Columbia) with the highest opioid overdose death rates and 6 prescriptions per 100 000 were dispensed in the 39 remaining states. The number of naloxone prescriptions dispensed was associated with the legal mandate for naloxone coprescription (incidence rate ratio [IRR], 7.75; 95% CI, 1.22-49.35). Implementation of the naloxone coprescription mandate was associated with an estimated 214 additional naloxone prescriptions dispensed per month in the period following the mandates, holding all other variables constant. Among covariates, naloxone access laws (IRR, 1.37; 1.05-1.78), opioid overdose death rates (IRR, 1.06; 95% CI, 1.04-1.08), the percentage of naloxone prescriptions paid by third-party payers (IRR 1.009; 1.008-1.010), and time (IRR, 1.06; 95% CI, 1.05-1.07) were significantly associated with naloxone prescription dispensing. Conclusions and Relevance: These study findings suggest that legally mandated naloxone prescription for those at risk for opioid overdose may be associated with substantial increases in naloxone dispensing and further reduction in opioid-related harm.

The changing landscape of naloxone availability in the United States, 2011 - 2017.

Opioid overdose deaths have been on the rise in the United States since 1999. Naloxone is a competitive opioid antagonist that rapidly reverses opioid overdose. The implementation of naloxone access laws and development of naloxone formulations that can be administered by laypersons have coincided with changes in the landscape of naloxone availability in the United States. Using data from IQVIA's National Prescription Audit® we present the number of naloxone prescriptions dispensed quarterly from 2011 through the second quarter of 2017. The data demonstrate that nationwide naloxone dispensing increased nearly eight-fold from the fourth quarter of 2015 to the second quarter of 2017. Narcan® was the most commonly prescribed naloxone formulation as of the second quarter of 2017, accounting for 68% of prescriptions during that quarter followed by Evzio® (20%). There was considerable variability in the extent to which states experienced increases in naloxone dispensing, which may represent a general state-specific response to the opioid crisis, rather than direct association with opioid overdose death rates in a particular state. Although naloxone access laws continue to increase the amount of naloxone dispensed, cost remains a concern in terms of wide distribution of the life-saving medication.

Rural and Appalachian Disparities in Neonatal Abstinence Syndrome Incidence and Access to Opioid Abuse Treatment.

OBJECTIVE: Incidence of neonatal abstinence syndrome (NAS) is increasing due to the rise in opioid use. Rural states like Kentucky have been disproportionally impacted by opioid abuse, and this study determines NAS burden nationally and in Kentucky while quantifying differences in access to care between Appalachian and non-Appalachian counties. METHODS: NAS rates were calculated using National (2013) and Kentucky (2008-2014) National Inpatient Sample discharge data. Births were identified using International Classification of Diseases v9 code 779.5 and live birth codes V30.x-V38.x. Counties were classified as rural, micropolitan, or metropolitan using census data. Proximity analysis was conducted via mapping from ZIP code centroid to nearest opioid treatment facility. Distance to treatment facilities was calculated and then compared using nonparametric testing for counties by rural and Appalachian status. RESULTS: NAS cases tripled from 2008 to 2014 in Kentucky counties, with a 2013 NAS rate more than double the national NAS rate. Rural and Appalachian counties experienced an NAS increase per 1,000 births that was 2-2.5 times higher than urban/non-Appalachian counties, with a greater number of NAS births overall in Appalachian counties. All opioid treatment facility types were further from rural patients than micropolitan/metropolitan patients (P < .001), as well as further for Appalachians versus non-Appalachians (P < .001, all facility types). CONCLUSIONS: NAS burden disparately affects rural and Appalachian Kentucky counties, while treatment options are disproportionately further away for these residents. Policy efforts to increase NAS prevention and encourage opioid abuse treatment uptake in pregnant women should address rural and Appalachian disparities.

Retrospective analysis of health claims to evaluate pharmacotherapies with potential for repurposing: Association of bupropion and stimulant use disorder remission.

Drug repurposing is the identification of novel indication(s) for existing medications. Health claims data provide a burgeoning resource to evaluate pharmacotherapies with repurposing potential. To demonstrate a workflow for drug repurposing using claims data, we assessed the association between prescription of bupropion and stimulant use disorder (StUD) remission. Using the Truven Marketscan database, 96,156 individuals with a StUD were identified. Logistic regression was used to model the association between new bupropion prescriptions and remission while controlling for age, sex, region, StUD severity, antidepressant co-prescriptions, and comorbid mood and attention disorders. Prescription of bupropion within 30 days offirst documented StUD diagnosis increased odds of a subsequent remission diagnosis by 2.1 times (99% confidence interval: 1.09-3.89) in individuals with an amphetamine use disorder, but not those with a cocaine use disorder. This work provides a framework for reverse-translational drug repurposing, which may be applied to many other medical conditions.

Medicaid program choice, inertia and adverse selection.

In 2012, Kentucky implemented Medicaid managed care statewide, auto-assigned enrollees to three plans, and allowed switching. Using administrative data, we find that the state's auto-assignment algorithm most heavily weighted cost-minimization and plan balancing, and placed little weight on the quality of the enrollee-plan match. Immobility - apparently driven by health plan inertia - contributed to the success of the cost-minimization strategy, as more than half of enrollees auto-assigned to even the lowest quality plans did not opt-out. High-cost enrollees were more likely to opt-out of their auto-assigned plan, creating adverse selection. The plan with arguably the highest quality incurred the largest initial profit margin reduction due to adverse selection prior to risk adjustment, as it attracted a disproportionate share of high-cost enrollees. The presence of such selection, caused by differential degrees of mobility, raises concerns about the long run viability of the Medicaid managed care market without such risk adjustment.

Empirical Assessment of the Impact of Low-Cost Generic Programs on Adherence-Based Quality Measures.

In the United States, federally-funded health plans are mandated to measure the quality of care. Adherence-based medication quality metrics depend on completeness of administrative claims data for accurate measurement. Low-cost generic programs (LCGPs) cause medications fills to be missing from claims data as medications are not adjudicated through a patient's insurance. This study sought to assess the magnitude of the impact of LCGPs on these quality measures. Data from the 2012-2013 Medical Expenditure Panel Survey (MEPS) were used. Medication fills for select medication classes were classified as LCGP fills and individuals were classified as never, sometimes, and always users of LCGPs. Individuals were classified based on insurance type (private, Medicare, Medicaid, dual-eligible). The proportion of days covered (PDC) was calculated for each medication class and the proportion of users with PDC ≥ 0.80 was reported as an observed metric for what would be calculated based on claims data and a true metric which included missing medication fills due to LCGPs. True measures of adherence were higher than the observed measures. The effect's magnitude was highest for private insurance and for medication classes utilized more often through LCGPs. Thus, medication-based quality measures may be underestimated due to LCGPs.