Publications

2023

Austin, Anna E, Christine Piette Durrance, Katherine A Ahrens, Qingwen Chen, Lindsey Hammerslag, Mary Joan McDuffie, Jeffery Talbert, Paul Lanier, Julie M Donohue, and Marian Jarlenski. (2023) 2023. “Duration of Medication for Opioid Use Disorder During Pregnancy and Postpartum by Race/Ethnicity: Results from 6 State Medicaid Programs.”. Drug and Alcohol Dependence 247: 109868. https://doi.org/10.1016/j.drugalcdep.2023.109868.

BACKGROUND: Medication for opioid use disorder (MOUD) is evidence-based treatment during pregnancy and postpartum. Prior studies show racial/ethnic differences in receipt of MOUD during pregnancy. Fewer studies have examined racial/ethnic differences in MOUD receipt and duration during the first year postpartum and in the type of MOUD received during pregnancy and postpartum.

METHODS: We used Medicaid administrative data from 6 states to compare the percentage of women with any MOUD and the average proportion of days covered (PDC) with MOUD, overall and by type of MOUD, during pregnancy and four postpartum periods (1-90 days, 91-180 days, 181-270 days, and 271-360 days postpartum) among White non-Hispanic, Black non-Hispanic, and Hispanic women diagnosed with OUD.

RESULTS: White non-Hispanic women were more likely to receive any MOUD during pregnancy and all postpartum periods compared to Hispanic and Black non-Hispanic women. For all MOUD types combined and for buprenorphine, White non-Hispanic women had the highest average PDC during pregnancy and each postpartum period, followed by Hispanic women and Black non-Hispanic women (e.g., for all MOUD types, 0.49 vs. 0.41 vs. 0.23 PDC, respectively, during days 1-90 postpartum). For methadone, White non-Hispanic and Hispanic women had similar average PDC during pregnancy and postpartum, and Black non-Hispanic women had substantially lower PDC.

CONCLUSIONS: There are stark racial/ethnic differences in MOUD during pregnancy and the first year postpartum. Reducing these inequities is critical to improving health outcomes among pregnant and postpartum women with OUD.

Hammerslag, Lindsey, Jeffery Talbert, Julie M Donohue, Michael Sharbaugh, Katherine Ahrens, Lindsay Allen, Anna E Austin, et al. (2023) 2023. “Urine Drug Testing Among Medicaid Enrollees Initiating Buprenorphine Treatment for Opioid Use Disorder Within 9 MODRN States.”. Drug and Alcohol Dependence 250: 110875. https://doi.org/10.1016/j.drugalcdep.2023.110875.

BACKGROUND: Treatment guidelines recommend regular urine drug testing (UDT) for persons initiating buprenorphine for opioid use disorder (OUD). However, little is known about UDT utilization. We describe state variation in UDT utilization and examine demographic, health, and health care utilization factors associated with UDT in Medicaid.

METHODS: We used Medicaid claims and enrollment data from persons initiating buprenorphine treatment for OUD during 2016-2019 in 9 states (DE, KY, MD, ME, MI, NC, PA, WI, WV). The main outcome was at least 1 UDT within 180 days of buprenorphine initiation, the secondary outcome was at least 3. Logistic regression models included demographics, pre-initiation comorbidities, and health service use. State estimates were pooled using meta-analysis.

RESULTS: The study cohort included 162,437 Medicaid enrollees initiating buprenorphine. The percent receiving ≥1 UDT varied from 62.1% to 89.8% by state. In the pooled analysis, enrollees with pre-initiation UDT had much higher odds of ≥1 UDT after initiation (aOR=3.83, 3.09-4.73); odds were also higher for enrollees with HIV, HCV, and/or HBV infection (aOR=1.25, 1.05-1.48) or who initiated in later years (2018 v 2016: aOR=1.39, 1.03-1.89; 2019 v 2016: aOR=1.67, 1.24-2.25). The odds of having ≥3 UDT were lower with pre-initiation opioid overdose (aOR=0.79, 0.64-0.96) and higher with pre-initiation UDT (aOR=2.63, 2.13-3.25) or OUD care (aOR=1.35, 1.04-1.74). The direction of associations with demographics varied by state.

CONCLUSIONS: Rates of UDT increased over time and there was variability among states in UDT rates and demographic predictors of UDT. Pre-initiation conditions, UDT, and OUD care were associated with UDT.

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.

Jiang, Xinyi, Hyun Jin Song, Ching-Yuan Chang, Debbie Wilson, Jingchuan Guo, Wei-Hsuan Lo-Ciganic, and Haesuk Park. (2023) 2023. “Disparities in Access to Hepatitis C Treatment Among Arizona Medicaid Beneficiaries With Chronic Hepatitis C.”. Medical Care 61 (2): 81-86. https://doi.org/10.1097/MLR.0000000000001801.

BACKGROUND: High costs of direct-acting antivirals (DAAs) have led to their restricted access for patients with hepatitis C virus (HCV).

OBJECTIVE: The aim was to assess how HCV treatment access and predictors of HCV treatment changed in the post-DAA period compared with pre-DAA period.

METHODS: A retrospective cohort study using Arizona Medicaid data was conducted for patients with HCV to compare treatment initiation rates between pre-DAA (January 2008-October 2013) and post-DAA (November 2013-December 2018) periods. Multivariable logistic regression was used, controlling for demographic and clinical variables.

RESULTS: Twenty-four thousand and ninety and 28,756 patients during the pre-DAA and post-DAA periods were identified. Overall, 12.6% were treated in the post-DAA period compared with 7.8% in the pre-DAA period ( P <0.001). The relative increase in the HCV treatment initiation rate from the pre-DAA to the post-DAA period was significant greater for Black beneficiaries compared with White beneficiaries ( P =0.002). Hispanic beneficiaries were less likely to be treated in the post-DAA period [adjusted odds ratios (aOR): 0.88; CI: 0.79-0.98] compared with White beneficiaries. Those with mental illness (aOR: 0.71; 95% CI: 0.63-0.80) and substance use disorders (aOR: 0.63; 95% CI: 0.58-0.68) were less likely to be treated in the post-DAA period.

CONCLUSIONS: Although treatment initiation increased and disparities for Black beneficiaries compared with White beneficiaries attenuated in the post-DAA period, only 13% of Arizona Medicaid patients with HCV received DAA treatment. Disparities in DAA access remained among Hispanic patients and those with mental illness and substance use disorders.

Park, Haesuk, Hye-Rim Kang, Pei-Lin Huang, Wei-Hsuan Lo-Ciganic, Christina E DeRemer, Debbie Wilson, and Eric A Dietrich. (2023) 2023. “Comparative Effectiveness and Safety of Extended Anticoagulant Therapy Among Medicare Beneficiaries With Venous Thromboembolism.”. Clinical and Translational Science 16 (1): 128-39. https://doi.org/10.1111/cts.13433.

Guidelines recommend an extended course of anticoagulation therapy for patients who experienced venous thromboembolism (VTE) without transient provocation, however, optimal duration remains uncertain. We assessed effectiveness and safety of extended use of apixaban and warfarin greater than 6 months of initial treatment in patients with VTE. We conducted a retrospective cohort study of Medicare beneficiaries aged greater than or equal to 18 years with deep vein thrombosis or pulmonary embolism. Patients were required to have initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of initial anticoagulant treatment, and received extended phase treatment with apixaban (the apixaban group) or warfarin (the warfarin group) or no extended therapy. Multivariable Cox proportional hazards modeling with inverse probability treatment weighting was used to compare recurrent VTE, mortality, and major bleeding risks among the three groups. Mean extended-treatment duration was up to 10 months and 14 months in apixaban and warfarin groups, respectively. Compared with no extended treatment, apixaban use was associated with decreased risks of recurrent VTE (hazard ratio [HR] = 0.08, [95% confidence interval [CI]: 0.01-0.41]) and mortality (HR = 0.37, [95% CI: 0.27-0.51]) without increased major bleeding risk (HR = 1.29, [95% CI: 0.68-2.45]); warfarin use was associated not with recurrent VTE risk change but with increased major bleeding risk (HR = 2.14, [95% CI: 1.26-3.65]) and decreased mortality risk (HR = 0.39, [95% CI: 0.29-0.51]). Compared with warfarin, apixaban use was associated with decreased recurrent VTE (HR = 0.13, [95% CI: 0.03-0.63]) and major bleeding (HR = 0.56, [95% CI: 0.32-0.98]) risks. Subgroup and sensitivity analyses (e.g., intention-to-treat) findings remained consistent. Compared with warfarin or no extended therapy, extended-apixaban use was associated with reduced risk of recurrent VTE without increased major bleeding risk. Continuing anticoagulant therapy with apixaban greater than 6 months may be effective and safe.

Chang, Ching-Yuan, Haesuk Park, Juan M Hincapie-Castillo, Coy D Heldermon, Vakaramoko Diaby, Seonkyeong Yang, Debbie L Wilson, and Wei-Hsuan Lo-Ciganic. (2023) 2023. “Trends, Characteristics, Race, and Ethnicity Associated With Nonadherence to Antidepressants Among Breast Cancer Survivors With Depression.”. Journal of Managed Care & Specialty Pharmacy 29 (4): 431-45. https://doi.org/10.18553/jmcp.2023.29.4.431.

BACKGROUND: Breast cancer is the most diagnosed cancer in the United States, and half of breast cancer survivors experience major depressive disorders (hereafter depression). Healthcare Effectiveness Data and Information Set (HEDIS) quality measures evaluating depression treatment practices recommend uninterrupted antidepressant treatment for 3 months in the acute phase and 3 months in the continuation phase for the general population. However, little is known about the extent of and trends in antidepressant nonadherence among breast cancer survivors with depression, which may impact adherence to breast cancer treatment, potentially leading to breast cancer recurrence and other adverse outcomes. OBJECTIVE: To examine the trends and characteristics associated with antidepressant nonadherence among breast cancer survivors with depression in the United States. METHODS: We conducted cross-sectional analyses of Surveillance, Epidemiology, and End Results linked with Medicare data (2010-2019) for women with breast cancer and depression who newly initiated antidepressant use. Using HEDIS measures of nonadherence (ie, antidepressant prescription coverage ≤84 days of the 114-day acute phase or ≤180 days of the 231-day continuation phase), we calculated the annual crude prevalence of antidepressant nonadherence and examined trends using unadjusted logistic regression. Multivariable logistic regression identified characteristics associated with antidepressant nonadherence. RESULTS: Among 9,452 eligible breast cancer survivors with depression (aged ≥65 years = 84% and White race = 82%), the crude prevalence of antidepressant nonadherence decreased from 2010 to 2019 for both the acute (49% to 40%; Ptrend<0.001) and continuation (67% to 57%; Ptrend<0.001) phases. Factors significantly associated with higher odds of antidepressant nonadherence in both the acute and continuation phases included Black race (odds ratios [ORs] [95% CI] for the acute/continuation phases: 2.0 [1.7-2.4]/2.0 [1.7-2.3]) and Hispanic ethnicity (1.5 [1.1-1.9]/2.2 [1.6-2.9]) compared with White race; receiving the first antidepressant from an oncologist vs a psychiatrist (1.4 [1.1-1.8]/1.6 [1.2-2.0]); and using antidepressants not recommended for older adults by the Beers criteria (2.2 [1.6-2.9]/2.0 [1.4-2.7]). Factors associated with lower odds of antidepressant nonadherence in both phases included receiving lymph node dissection (0.7 [0.5-0.9]/0.7 [0.5-0.9]), receiving endocrine therapy (0.9 [0.8-0.9]/0.8 [0.7-0.9]), having a higher National Cancer Institute comorbid index (0.8 [0.7-0.8]/0.9 [0.8-0.9]), having a follow-up visit with a psychiatrist (0.9 [0.8-0.9]/0.9 [0.8-0.9]), and switching to different antidepressants (0.7 [0.6-0.8]/0.7 [0.7-0.8]). CONCLUSIONS: Despite antidepressant nonadherence prevalence decreasing from 2010 to 2019, over half of breast cancer survivors with depression and Medicare were nonadherent in the continuation phase. Patients with identified nonadherence risk factors may benefit from close monitoring and targeted interventions. DISCLOSURES: Wei-Hsuan Lo-Ciganic reported grants from the National Institute on Drug Abuse (R01DA044985 and R01DA050676), the National Institute on Aging (R21AG060308), the National Institute of Mental Health (R01MH121907), Merck Sharp & Dohme, Bristol Myers Squibb, the Richard King Mellon Foundation at the University of Pittsburgh, the Clinical and Translational Science Institute of the University of Florida, the Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation, and the US Department of Veterans Affairs outside the submitted work; in addition, Wei-Hsuan Lo-Ciganic has a patent pending for U1195.70174US00. Haesuk Park reported grants from Bristol Myers Squibb/Pfizer Alliance American Thrombosis Investigator Initiated Research Program (ARISTA-USA) outside the submitted work. Juan M. Hincapie-Castillo reported grants from Merck outside the submitted work. Debbie Wilson reported grants from the National Institute on Drug Abuse, the National Institute on Aging, Merck Sharp & Dohme, and Bristol Myers Squibb outside the submitted work; and serving as an editorial board member for the Journal of Pharmacy Technology. Ching-Yuan Chang's contributions to this manuscript were made while at the University of Florida College of Pharmacy. Ching-Yuan Chang is currently employed by Vertex Pharmaceuticals, Inc. Vertex did not fund or have any involvement in this study or publication. Vakaramoko Diaby is currently employed by Otsuka, Inc. Otsuka did not fund or have any involvement in this study or publication. No other disclosures were reported.

Kang, Hye-Rim, Bobby L Jones, Wei-Hsuan Lo-Ciganic, Christina E DeRemer, Eric A Dietrich, Pei-Lin Huang, and Haesuk Park. (2023) 2023. “Trajectories of Adherence to Extended Treatment With Warfarin and Risks of Recurrent Venous Thromboembolism and Major Bleeding.”. Research and Practice in Thrombosis and Haemostasis 7 (3): 100131. https://doi.org/10.1016/j.rpth.2023.100131.

BACKGROUND: Little is published about warfarin therapy adherence patterns beyond 6 months of initial anticoagulant treatment and their association with effectiveness and safety for patients with venous thromboembolism (VTE).

OBJECTIVES: To compare the risks of recurrent VTE and major bleeding during extended treatment between adherence patterns using MarketScan Commercial and Medicare Supplemental databases (2013-2019).

METHODS: In a retrospective cohort study, we included patients with incident VTE who completed an initial 6-month anticoagulant treatment and received either warfarin or no extended therapy. Group-based trajectory models were used to identify distinct extended treatment trajectories. Associations between the trajectories and risk of hospitalization due to recurrent VTE and major bleeding were assessed using inverse probability treatment-weighted Cox proportional hazards models.

RESULTS: Compared with no extended treatment, consistently high warfarin adherence was associated with a significantly decreased risk of hospitalization due to recurrent VTE (hazard ratio [HR] = 0.23; 95% CI, 0.12-0.45), but gradually (HR = 0.29; 95CI, 0.08-1.06) or rapidly declining (HR = 0.14; 95% CI, 0.02-1.24) adherence showed no association with the risk of hospitalization due to recurrent VTE. Compared with no extended treatment, warfarin extended therapy was associated with an increased risk of hospitalization due to major bleeding regardless of adherence patterns (consistently high: HR = 2.08; 95% CI, 1.18-3.64, gradually declining: HR = 2.10; 95% CI, 0.74-5.95, and rapidly declining: HR = 9.19; 95% CI, 4.38-19.29). However, compared with rapidly declining adherence, consistently high (HR = 0.23; 95% CI, 0.11-0.47) and gradually declining (HR = 0.23; 95% CI, 0.08-0.64) adherence were associated with decreased risk of hospitalization due to major bleeding.

CONCLUSION: The findings indicated that consistently high adherence to extended warfarin treatment was associated with a decreased risk of hospitalization due to recurrent VTE but an increased risk of hospitalization due to major bleeding compared with no extended treatment.

Wang, Yanning, Debbie L Wilson, Deanna Fernandes, Lauren E Adkins, Ashley Bantad, Clint Copacia, Nilay Dharma, et al. (2023) 2023. “Deprescribing Strategies for Opioids and Benzodiazepines With Emphasis on Concurrent Use: A Scoping Review.”. Journal of Clinical Medicine 12 (5). https://doi.org/10.3390/jcm12051788.

While the Food and Drug Administration's black-box warnings caution against concurrent opioid and benzodiazepine (OPI-BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995-08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0). Among the three studies deprescribing concurrent use (success rates of 21-100%), two evaluated a 3-week rehabilitation program, and one assessed a 24-week primary care intervention for veterans. Initial opioid dose deprescribing rates ranged from (1) 10-20%/weekday followed by 2.5-10%/weekday over three weeks to (2) 10-25%/1-4 weeks. Initial benzodiazepine dose deprescribing rates ranged from (1) patient-specific reductions over three weeks to (2) 50% dose reduction for 2-4 weeks, followed by 2-8 weeks of dose maintenance and then a 25% reduction biweekly. Among the 26 guidelines identified, 22 highlighted the risks of co-prescribing OPI-BZD, and 4 provided conflicting recommendations on the OPI-BZD deprescribing sequence. Thirty-five states' websites provided resources for opioid deprescription and three states' websites had benzodiazepine deprescribing recommendations. Further studies are needed to better guide OPI-BZD deprescription.