Publications

2023

Hughes, Ashley M, Erica Lin, Raza A Hussain, Gretchen Gibson, Marianne Jurasic, Lisa K Sharp, Colin C Hubbard, et al. (2023) 2023. “The Feasibility of Academic Detailing for Acute Oral Pain Management in Outpatient Dentistry: A Pilot Study.”. Journal of the American Pharmacists Association : JAPhA 63 (1): 158-163.e6. https://doi.org/10.1016/j.japh.2022.08.001.

BACKGROUND: Opioids are overprescribed in the outpatient dental setting. Therefore, opportunities exist for opioid stewardship.

OBJECTIVES: The purpose of this pilot study was to test the feasibility of an academic detailing (AD) intervention to promote appropriate prescribing of opioids in outpatient dentistry.

METHODS: We implemented an AD intervention targeting management of acute oral pain in a Midwestern Veterans Affairs outpatient dental facility. The intervention targeted dentists who actively prescribed opioids at the time of the study. The pilot study tested feasibility, adoption, and acceptance of the AD campaign. Visit-based prescribing rates were obtained from the Veterans Health Administration's Corporate Data Warehouse for baseline and postintervention using difference-in-differences analyses to detect potential changes in health service outcomes.

RESULTS: Results indicate moderate levels of feasibility through participation rates (n = 5, 55.5%) and high levels of organizational readiness for change (average of 88.6% agree to strongly agree). Furthermore, fidelity of the AD intervention was high. Adoption measures show moderate indication of motivation to change, and trends suggest that participating dentists decreased their visit-based opioid prescribing rates (P > 0.05).

CONCLUSION: The intervention demonstrated feasibility with some indications of adoption of intervention techniques and decrease in opioid prescribing. We further recommend working closely with frontline providers to gather feedback and buy-in before scaling and implementing the AD campaign.

Frank, David A, Amber E Johnson, Leslie R M Hausmann, Walid F Gellad, Eric T Roberts, and Ravy K Vajravelu. (2023) 2023. “Disparities in Guideline-Recommended Statin Use for Prevention of Atherosclerotic Cardiovascular Disease by Race, Ethnicity, and Gender : A Nationally Representative Cross-Sectional Analysis of Adults in the United States.”. Annals of Internal Medicine 176 (8): 1057-66. https://doi.org/10.7326/M23-0720.

BACKGROUND: Although statins are a class I recommendation for prevention of atherosclerotic cardiovascular disease and its complications, their use is suboptimal. Differential underuse may mediate disparities in cardiovascular health for systematically marginalized persons.

OBJECTIVE: To estimate disparities in statin use by race-ethnicity-gender and to determine whether these potential disparities are explained by medical appropriateness of therapy and structural factors.

DESIGN: Cross-sectional analysis.

SETTING: National Health and Nutrition Examination Survey from 2015 to 2020.

PARTICIPANTS: Persons eligible for statin therapy based on 2013 and 2018 American College of Cardiology/American Heart Association blood cholesterol guidelines.

MEASUREMENTS: The independent variable was race-ethnicity-gender. The outcome of interest was use of a statin. Using the Institute of Medicine framework for examining unequal treatment, we calculated adjusted prevalence ratios (aPRs) to estimate disparities in statin use adjusted for age, disease severity, access to health care, and socioeconomic status relative to non-Hispanic White men.

RESULTS: For primary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors among non-Hispanic Black men (aPR, 0.73 [95% CI, 0.59 to 0.88]) and non-Mexican Hispanic women (aPR, 0.74 [CI, 0.53 to 0.95]). For secondary prevention, we identified a lower prevalence of statin use that was not explained by measurable differences in disease severity or structural factors for non-Hispanic Black men (aPR, 0.81 [CI, 0.64 to 0.97]), other/multiracial men (aPR, 0.58 [CI, 0.20 to 0.97]), Mexican American women (aPR, 0.36 [CI, 0.10 to 0.61]), non-Mexican Hispanic women (aPR, 0.57 [CI, 0.33 to 0.82), non-Hispanic White women (aPR, 0.69 [CI, 0.56 to 0.83]), and non-Hispanic Black women (aPR, 0.75 [CI, 0.57 to 0.92]).

LIMITATION: Cross-sectional data; lack of geographic, language, or statin-dose data.

CONCLUSION: Statin use disparities for several race-ethnicity-gender groups are not explained by measurable differences in medical appropriateness of therapy, access to health care, and socioeconomic status. These residual disparities may be partially mediated by unobserved processes that contribute to health inequity, including bias, stereotyping, and mistrust.

PRIMARY FUNDING SOURCE: National Institutes of Health.

Dickson, Sean R, Nico Gabriel, Walid F Gellad, and Inmaculada Hernandez. (2023) 2023. “Assessment of Commercial and Mandatory Discounts in the Gross-to-Net Bubble for the Top Insulin Products From 2012 to 2019.”. JAMA Network Open 6 (6): e2318145. https://doi.org/10.1001/jamanetworkopen.2023.18145.

IMPORTANCE: Insulin list prices have grown substantially since 2010, but net prices have declined since 2015 because of manufacturer discounts, leading to an increasingly large difference between list and net prices of drugs often called the gross-to-net bubble. It remains unclear to what extent the gross-to-net bubble represents voluntary manufacturer discounts negotiated in commercial and Medicare Part D markets (hereafter called commercial discounts) vs mandatory discounts under the Medicare Part D coverage gap, Medicaid, and the 340B program.

OBJECTIVE: To decompose the overall gross-to-net bubble of leading insulin products into discount types.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation obtained data from Medicare and Medicaid claims and spending dashboards, Medicare Part D Prescriber Public Use File, and SSR Health for the top 4 commonly used insulin products: Lantus, Levemir, Humalog, and Novolog. The gross-to-net bubble, which represents total discounts, was estimated for each insulin product and year (from 2012 to 2019). Analyses were conducted in June to December 2022.

MAIN OUTCOMES AND MEASURES: The gross-to-net bubble was decomposed into 4 discount types: (1) Medicare Part D coverage gap discounts, (2) Medicaid discounts, (3) 340B discounts, and (4) commercial discounts. Coverage gap discounts were estimated using Medicare Part D claims data. Medicaid and 340B discounts were estimated using a novel algorithm that accounted for best prices set by commercial discounts.

RESULTS: Total discounts for the 4 insulin products increased from $4.9 billion to $22.0 billion. Commercial discounts represented a majority of all discounts, increasing from 71.7% of the gross-to-net bubble in 2012 ($3.5 billion) to 74.3% ($16.4 billion) in 2019. Among mandatory discounts, coverage gap discounts remained relatively consistent as a proportion of discounts (5.4% in 2012 vs 5.3% in 2019). Medicaid rebates decreased as a proportion of total discounts, from 19.7% in 2012 to 10.6% in 2019. The 340B discounts increased as a proportion of total discounts from 3.3% in 2012 to 9.8% in 2019. Results for the contribution of discount types to the gross-to-net bubble were consistent across insulin products.

CONCLUSIONS AND RELEVANCE: Results of a decomposition of the gross-to-net bubble for leading insulin products suggest that commercial discounts play a growing role in lowering net sales compared with mandatory discounts.

Pickering, Aimee N, Xinhua Zhao, Florentina E Sileanu, Elijah Z Lovelace, Liam Rose, Aaron L Schwartz, Allison H Oakes, et al. (2023) 2023. “Prevalence and Cost of Care Cascades Following Low-Value Preoperative Electrocardiogram and Chest Radiograph Within the Veterans Health Administration.”. Journal of General Internal Medicine 38 (2): 285-93. https://doi.org/10.1007/s11606-022-07561-x.

BACKGROUND: Low-value care cascades, defined as the receipt of downstream health services potentially related to a low-value service, can result in harm to patients and wasteful healthcare spending, yet have not been characterized within the Veterans Health Administration (VHA).

OBJECTIVE: To examine if the receipt of low-value preoperative testing is associated with greater utilization and costs of potentially related downstream health services in Veterans undergoing low or intermediate-risk surgery.

DESIGN: Retrospective cohort study using VHA administrative data from fiscal years 2017-2018 comparing Veterans who underwent low-value preoperative electrocardiogram (EKG) or chest radiograph (CXR) with those who did not.

PARTICIPANTS: National cohort of Veterans at low risk of cardiopulmonary disease undergoing low- or intermediate-risk surgery.

MAIN MEASURES: Difference in rate of receipt and attributed cost of potential cascade services in Veterans who underwent low-value preoperative testing compared to those who did not KEY RESULTS: Among 635,824 Veterans undergoing low-risk procedures, 7.8% underwent preoperative EKG. Veterans who underwent a preoperative EKG experienced an additional 52.4 (95% CI 47.7-57.2) cascade services per 100 Veterans, resulting in $138.28 (95% CI 126.19-150.37) per Veteran in excess costs. Among 739,005 Veterans undergoing low- or intermediate-risk surgery, 3.9% underwent preoperative CXR. These Veterans experienced an additional 61.9 (95% CI 57.8-66.1) cascade services per 100 Veterans, resulting in $152.08 (95% CI $146.66-157.51) per Veteran in excess costs. For both cohorts, care cascades consisted largely of repeat tests, follow-up imaging, and follow-up visits, with low rates invasive services.

CONCLUSIONS: Among a national cohort of Veterans undergoing low- or intermediate-risk surgeries, low-value care cascades following two routine low-value preoperative tests are common, resulting in greater unnecessary care and costs beyond the initial low-value service. These findings may guide de-implementation policies within VHA and other integrated healthcare systems that target those services whose downstream effects are most prevalent and costly.

Kim, Katherine Callaway, Tumader Khouja, Jacqueline M Burgette, Charlesnika T Evans, Gregory S Calip, Walid F Gellad, and Katie J Suda. (2023) 2023. “Trends in Dispensed Prescriptions for Opioids, Sedatives, Benzodiazepines, Gabapentin, and Stimulants to Children by General Dentists, 2012-2019.”. Pharmacoepidemiology and Drug Safety 32 (6): 625-34. https://doi.org/10.1002/pds.5589.

PURPOSE: Opioids, benzodiazepines and sedatives can manage dental pain, fear and anxiety but have a narrow margin of safety in children. General dentists may inappropriately prescribe gabapentin and stimulants. National evidence on dispensing rates of these high-alert medicines by dentists to children is limited.

METHODS: We utilize join-point regression to identify changes in fills for opioids, sedatives, benzodiazepines, gabapentin, and stimulants to children <18 years from 2012 to 2019 in a national dataset comprising 92% of dispensed outpatient prescriptions by dentists.

RESULTS: From 2012 to 2019, 3.8 million children filled prescriptions for high-alert drugs from general dentists. National quarterly dispensing of high-alert drugs decreased 63.1%, from 10456.0 to 3858.8 days per million. Opioids accounted for 69.4% of high-alert prescriptions. From 2012 to 2019, fills for opioids, sedatives, benzodiazepines, and stimulants decreased by 65.2% (7651.8 to 2662.7), 43.4% (810.9 to 458.7), 43.6% (785.7 to 442.7) and 89.3% (825.6 to 88.6 days per million), respectively. Gabapentin increased 8.1% (121.8 to 131.7 days per million). A significant decrease in high-alert fills occurred in 2016, (-6.0% per quarter vs. -1.6% pre-2016, P-value<0.001), especially for opioids (-7.0% vs. -1.2%, P-value<0.001). Older teenagers (15-17 years) received 42.5% of high-alert prescriptions. Low-income counties in the South were overrepresented among top-prescribing areas in 2019.

CONCLUSIONS: We found promising national decreases in fills for high-alert medicines to children by general dentists from 2012 to 2019. However, older teenagers and children in some counties continued to receive dental opioids at high rates. Future efforts should address non-evidence-based pain management in these groups.

Hernandez, Inmaculada, Meiqi He, Jingchuan Guo, Mina Tadrous, Nico Gabriel, Gretchen Swabe, Walid F Gellad, et al. (2023) 2023. “COVID-19 Pandemic and Trends in New Diagnosis of Atrial Fibrillation: A Nationwide Analysis of Claims Data.”. PloS One 18 (2): e0281068. https://doi.org/10.1371/journal.pone.0281068.

BACKGROUND: Atrial fibrillation (AF) is associated with a five-fold increased risk of stroke and a two-fold increased risk of death. We aimed to quantify changes in new diagnoses of AF following the onset of the COVID-19 pandemic. Investigating changes in new diagnoses of AF is of relevance because delayed diagnosis interferes with timely treatment to prevent stroke, heart failure, and death.

METHODS: Using De-identified Optum's Clinformatics® Data Mart, we identified 19,500,401 beneficiaries continuously enrolled for 12 months in 2016-Q3 2020 with no history of AF. The primary outcome was new AF diagnoses per 30-day interval. Secondary outcomes included AF diagnosis in the inpatient setting, AF diagnosis in the outpatient setting, and ischemic stroke as initial manifestation of AF. We constructed seasonal autoregressive integrated moving average models to quantify changes in new AF diagnoses after the onset of the COVID-19 pandemic (3/11/2020, date of pandemic declaration). We tested whether changes in the new AF diagnoses differed by race and ethnicity.

RESULTS: The average age of study participants was 51.0±18.5 years, and 52% of the sample was female. During the study period, 2.7% of the study sample had newly-diagnosed AF. New AF diagnoses decreased by 35% (95% CI, 21%-48%) after the onset of the COVID-19 pandemic, from 1.14 per 1000 individuals (95% CI, 1.05-1.24) to 0.74 per 1000 (95% CI, 0.64 to 0.83, p-value<0.001). New AF diagnoses decreased by 37% (95% CI, 13%- 55%) in the outpatient setting and by 29% (95% CI, 14%-43%) in the inpatient setting. The decrease in new AF diagnoses was similar across racial and ethnic subgroups.

CONCLUSION: In a nationwide cohort of 19.5 million individuals, new diagnoses of AF decreased substantially following the onset of the COVID-19 pandemic. Our findings evidence pandemic disruptions in access to care for AF, which are concerning because delayed diagnosis interferes with timely treatment to prevent complications.

Dickson, Sean, Nico Gabriel, Walid F Gellad, and Inmaculada Hernandez. (2023) 2023. “Estimated Changes in Insulin Prices and Discounts After Entry of New Insulin Products, 2012-2019.”. JAMA Health Forum 4 (6): e231430. https://doi.org/10.1001/jamahealthforum.2023.1430.

IMPORTANCE: Despite the political salience of insulin prices, no study to date has quantified trends in insulin prices that account for manufacturer discounts (net prices).

OBJECTIVE: To describe trends in insulin list prices and net prices faced by payers from 2012 to 2019 and estimate changes in net prices after the 2015 to 2017 entry of new insulin products.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included an analysis of Medicare, Medicaid, and SSR Health drug pricing data from January 1, 2012, to December 31, 2019. Data analyses were performed from June 1, 2022, to October 31, 2022.

EXPOSURES: US sales of insulin products.

MAIN OUTCOMES AND MEASURES: Net prices faced by payers were estimated for insulin products as list prices minus manufacturer discounts negotiated in commercial and Medicare Part D markets (ie, commercial discounts). Trends in net prices were evaluated before and after the entry of new insulin products.

RESULTS: Net prices of long-acting insulin products increased at an annual rate of 23.6% from 2012 to 2014 but decreased at an annual rate of 8.3% after the introduction of insulin glargine (Toujeo and Basaglar) and degludec (Tresiba) in 2015. Net prices of short-acting insulin increased at an annual rate of 5.6% from 2012 to 2017 but then decreased from 2018 to 2019 after the introduction of insulin aspart (Fiasp) and lispro (Admelog). For human insulin products, which did not experience entry of new products, net prices increased at an annual rate of 9.2% from 2012 to 2019. From 2012 to 2019, commercial discounts increased from 22.7% to 64.8% for long-acting insulin products, from 37.9% to 66.1% for short-acting insulin products, and from 54.9% to 63.1% for human insulin products.

CONCLUSIONS AND RELEVANCE: In this longitudinal study of US insulin products, results suggest that insulin prices substantially increased from 2012 to 2015, even after accounting for discounts. The introduction of new insulin products was followed by substantial discounting practices that lowered net prices faced by payers.

Yang, Lanting, Shangbin Tang, Meiqi He, Jingchuan Guo, Nico Gabriel, Gretchen Swabe, Walid F Gellad, et al. (2023) 2023. “COVID-19 Pandemic and Initiation of Treatment for Atrial Fibrillation: A Nationwide Analysis of Claims Data.”. BMC Cardiovascular Disorders 23 (1): 604. https://doi.org/10.1186/s12872-023-03614-z.

BACKGROUND: The COVID-19 pandemic profoundly disrupted the delivery of medical care. It remains unclear whether individuals diagnosed with new onset disease during the pandemic were less likely to initiate treatments after diagnosis. We sought to evaluate changes in the treatment initiation of patients newly diagnosed with atrial fibrillation (AF) after the onset of the COVID-19 pandemic.

METHODS: In this retrospective cohort study, we identified individuals with incident AF from 01/01/2016-09/30/2021 using Optum's de-identified Clinformatics® Data Mart Database. The primary outcome was initiation of oral anticoagulation (OAC) within 30 days of AF diagnosis. Secondary outcomes included initiation of OAC within 180 days of diagnosis, initiation of warfarin, direct oral anticoagulants (DOACs), rhythm control medications and electrical cardioversion within 30 days of diagnosis. We constructed interrupted time series analyses to examine changes in the outcomes following the onset of the pandemic.

RESULTS: A total of 573,524 patients (age 73.0 ± 10.9 years) were included in the study. There were no significant changes in the initiation of OAC, DOAC, and rhythm control medications associated with the onset of the pandemic. There was a significant decrease in initiation of electrical cardioversion associated with the onset of the pandemic. The rate of electronic cardioversion within 30 days of diagnosis decreased by 4.9% per 1,000 patients after the onset of the pandemic and decreased by about 35% in April 2020, compared to April 2019, from 5.53% to 3.58%.

CONCLUSION: The COVID-19 pandemic did not affect the OAC initiation within 30 days of AF diagnosis but was associated with a decline in the provision of procedures for patients newly diagnosed with AF.

Gellad, Walid F, Qingnan Yang, Kayleigh M Adamson, Courtney C Kuza, Jeanine M Buchanich, Ashley L Bolton, Stanley M Murzynski, et al. (2023) 2023. “Development and Validation of an Overdose Risk Prediction Tool Using Prescription Drug Monitoring Program Data.”. Drug and Alcohol Dependence 246: 109856. https://doi.org/10.1016/j.drugalcdep.2023.109856.

OBJECTIVES: To develop and validate a machine-learning algorithm to predict fatal overdose using Pennsylvania Prescription Drug Monitoring Program (PDMP) data.

METHODS: The training/testing (n = 3020,748) and validation (n = 2237,701) cohorts included Pennsylvania residents with a prescription dispensing from February 2018-September 2021. Potential predictors (n = 222) were measured in the 6 months prior to a random index date. Using a gradient boosting machine, we developed a 20-variable model to predict risk of fatal drug overdose in the 6 months after the index date.

RESULTS: Beneficiaries in the training (n = 1,812,448), testing (n = 1,208,300), and validation (n = 2,237,701) samples had similar age, with low rates of fatal overdose during 6-month follow up (0.12%, 0.12%, 0.04%, respectively). The validation c-statistic was 0.86 for predicting fatal overdose using 20 PDMP variables. When ranking individuals based on risk score, the prediction model more accurately identified fatal overdose at 6 months compared to using opioid dosage or opioid/benzodiazepine overlap, although the percentage of individuals in the highest risk percentile who died at 6 months was less than 1%.

CONCLUSIONS AND POLICY IMPLICATIONS: A gradient boosting machine algorithm predicting fatal overdose derived from twenty variables performed well in discriminating risk across testing and validation samples, improving on single factor risk measures like opioid dosage.

Bridges, Nora C, Rachel Taber, Abigail L Foulds, Todd M Bear, Renee M Cloutier, Brianna L McDonough, Adam J Gordon, et al. (2023) 2023. “Medications for Opioid Use Disorder in Rural Primary Care Practices: Patient and Provider Experiences.”. Journal of Substance Use and Addiction Treatment 154: 209133. https://doi.org/10.1016/j.josat.2023.209133.

INTRODUCTION: The opioid epidemic has exacted a significant toll in rural areas, yet adoption of medications for opioid use disorder (MOUD) lags. The Rural Access to Medication Assisted Treatment in Pennsylvania (RAMP) Project facilitated adoption of MOUD in rural primary care clinics. The purpose of this study was to gain a better understanding of the barriers and facilitators operating at multiple levels to access or provide MOUD in rural Pennsylvania.

METHODS: In total, the study conducted 35 semi-structured interviews with MOUD patients and MOUD providers participating in RAMP. Qualitative analysis incorporated both deductive and inductive approaches. The study team coded interviews and performed thematic analysis. Using a modified social-ecological framework, themes from the qualitative interviews are organized in five nested levels: individual, interpersonal, health care setting, community, and public policy.

RESULTS: Patients and providers agreed on many barriers (e.g., lack of providers, lack of transportation, insufficient rapport and trust in patient-provider relationship, and cost, etc.); however, their interpretation of the barrier, or indicated solution, diverged in meaningful ways. Patients described their experiences in broad terms pointing to the social determinants of health, as they highlighted their lives outside of the therapeutic encounter in the clinic. Providers focused on their professional roles, responsibilities, and operations within the primary care setting.

CONCLUSIONS: Providers may want to discuss barriers to treatment related to social determinants of health with patients, and pursue partnerships with organizations that seek to address those barriers. The findings from these interviews point to potential opportunities to enhance patient experience, increase access to and optimize processes for MOUD in rural areas, and reduce stigma against people with opioid use disorder (OUD) in the wider community.