Publications

2025

Wachterman, Melissa W, Stuart R Lipsitz, Erin Beilstein-Wedel, Walid F Gellad, Karl A Lorenz, and Nancy L Keating. (2025) 2025. “Temporal Trends in Opioid-Related Care and Pain Among Veterans at the End of Life.”. Journal of Pain and Symptom Management. https://doi.org/10.1016/j.jpainsymman.2025.03.032.

CONTEXT: In response to the opioid crisis, federal guidelines were implemented, including the Veterans Health Administration's (VA) Opioid Safety Initiative in 2013. The impact of policies on patients near the end of life is unknown.

OBJECTIVES: Examine temporal trends in opioid prescribing, pain, and opioid overdoses among Veterans near the end of life.

METHODS: Retrospective, time series analysis of VA decedents between October 2009 and September 2018 whose next-of-kin participated in VA's Bereaved Family Survey (BFS). Using multivariate regression to adjust for sociodemographic and clinical covariates, we examined temporal trends in outpatient opioid prescribing, uncontrolled pain based on BFS report, and opioid overdose-related hospitalizations, in the last month of life, overall and by clinical diagnosis (cancer versus non-cancer).

RESULTS: Among 79,409 decedents, mean daily outpatient opioid dose in morphine milligram equivalents in the last month of life decreased from 4.6 mg in 2010 to 2.1 mg in 2018 (adjusted change -0.20 mg/year; P < .001). Opioid overdose-related hospitalization decreased from 0.8% in 2010 to 0.1% in 2018 (adjusted percentage point [PP] change -0.06 PP/year; P < .001). Among the 63,965 Veterans with pain data, the percentage with frequent uncontrolled pain increased from 48.8% in 2010 to 52.2% in 2018 (adjusted PP change +1.37 PP/y; P < .001). Patterns were similar among patients with cancer versus non-cancer conditions.

CONCLUSIONS: Over a time period during which opioid safety initiatives were implemented, opioid prescribing near the end of life decreased, accompanied by decreases in opioid-related hospitalizations but increases in pain. These findings suggest that important tradeoffs may exist between reducing opioid-related serious adverse events and undertreating patient pain in the last month of life. Opioid prescribing guidelines could consider incorporating prognosis into recommendations.

Seedahmed, Mohamed I, Mohamed T Albirair, Aaron D Baugh, Walid F Gellad, Mehdi Nouraie, Kevin F Gibson, Mary A Whooley, Charles E McCulloch, Laura L Koth, and Mehrdad Arjomandi. (2025) 2025. “Trends in All-Cause Mortality Among US Veterans With Sarcoidosis, 2004-2022.”. Chest 167 (5): 1416-27. https://doi.org/10.1016/j.chest.2024.10.043.

BACKGROUND: Sarcoidosis is an idiopathic multiorgan disease with variable clinical outcomes. Comprehensive analysis of sarcoidosis mortality in US veterans is lacking.

RESEARCH QUESTION: What are the trends in all-cause mortality among US veterans with sarcoidosis, and how are these trends influenced by demographics, Black vs White racial disparities, and geographic variability in relationship to mortality?

STUDY DESIGN AND METHODS: Using Veterans Health Administration (VHA) electronic health records (EHRs), we conducted a population-based retrospective cohort study of adjusted all-cause mortality from 2004 through 2022 among veterans with a diagnosis of sarcoidosis who received care through the VHA. Demographics, region of residence, service branch, tobacco use, and comorbidities were extracted from the EHR. Annual trends in all-cause mortality and patient-level characteristics associated with mortality were examined with multivariable ungrouped Poisson regression. We visualized trends and analyzed state-by-state mortality using the marginal means procedure. In subgroup analysis (2015-2022), we considered the impact of neighborhood-level socioeconomic disparities using the Area Deprivation Index (ADI).

RESULTS: In all, 23,745 veterans received a diagnosis of sarcoidosis between 2004 and 2019 and were followed up through 2022. After adjustment, including age and sex, all-cause mortality increased annually by 4.7% (P < .0001) and was 6.4% higher in Black than White veterans (mortality rate ratio, 1.064; P = .02). A subgroup analysis comparing models with and without ADI adjustment showed no meaningful change in mortality trends. Risk factors for increased all-cause mortality included older age, male sex, Black race, Northeast residence, and lower risk with other service branches. Despite distinct geographical variations in mortality rates, no clear patterns emerged.

INTERPRETATION: Mortality among veterans with sarcoidosis is rising. Differences identified by service branch and higher risk among male Veterans raise questions about differences in environmental exposures. The narrower racial disparities and smaller impact of ADI than in other studies may highlight the role of universal health care access in achieving equitable outcomes.

Xue, Lingshu, Ruofei Yin, Evan S Cole, Wei-Hsuan Lo-Ciganic, Walid F Gellad, Julie Donohue, and Lu Tang. (2025) 2025. “Development and Evaluation of a Machine Learning Model to Predict Acute Care for Opioid Use Disorder Among Medicaid Enrollees Engaged in a Community-Based Treatment Program.”. Addiction (Abingdon, England). https://doi.org/10.1111/add.70079.

AIMS: To develop machine-learning algorithms for predicting the risk of a hospitalization or emergency department (ED) visit for opioid use disorder (OUD) (i.e. OUD acute events) in Pennsylvania Medicaid enrollees in the Opioid Use Disorder Centers of Excellence (COE) program and to evaluate the fairness of model performance across racial groups.

METHODS: We studied 20 983 United States Medicaid enrollees aged 18 years or older who had COE visits between April 2019 and March 2021. We applied multivariate logistic regression, least absolute shrinkage and selection operator models, random forests, and eXtreme Gradient Boosting (XGB), to predict OUD acute events following the initial COE visit. Our models included predictors at the system, patient, and regional levels. We assessed model performance using multiple metrics by racial groups. Individuals were divided into a low, medium and high-risk group based on predicted risk scores.

RESULTS: The training (n = 13 990) and testing (n = 6993) samples displayed similar characteristics (mean age 38.1 ± 9.3 years, 58% male, 80% White enrollees) with 4% experiencing OUD acute events at baseline. XGB demonstrated the best prediction performance (C-statistic = 76.6% [95% confidence interval = 75.6%-77.7%] vs. 72.8%-74.7% for other methods). At the balanced cutoff, XGB achieved a sensitivity of 68.2%, specificity of 70.0%, and positive predictive value of 8.3%. The XGB model classified the testing sample into high-risk (6%), medium-risk (30%), and low-risk (63%) groups. In the high-risk group, 40.7% had OUD acute events vs. 16.5% and 5.0% in the medium- and low-risk groups. The high- and medium-risk groups captured 44% and 26% of individuals with OUD events. The XGB model exhibited lower false negative rates and higher false positive rates in racial/ethnic minority groups than White enrollees.

CONCLUSIONS: New machine-learning algorithms perform well to predict risks of opioid use disorder (OUD) acute care use among United States Medicaid enrollees and improve fairness of prediction across racial and ethnic groups compared with previous OUD-related models.

Lussier, Mia E, Megan E Hamm, Balchandre N Kenkre, Eric A Wright, Adam J Gordon, Ajay D Wasan, Walid F Gellad, et al. (2025) 2025. “Clinician Perceptions of Electronic Health Record and Email Nudge Interventions to Prevent Unsafe Opioid Prescribing: A Qualitative Study.”. Journal of Opioid Management 21 (2): 121-30. https://doi.org/10.5055/jom.0913.

OBJECTIVE: We aimed to understand clinician perceptions of nudge interventions designed to prevent unsafe opioid prescribing for acute pain in primary care.

DESIGN: Semistructured interviews were conducted.

SETTING: Forty-eight practices across three healthcare systems were included.

PARTICIPANTS: Primary care clinicians who were exposed to nudge interventions as part of a randomized clinical trial were included.

INTERVENTIONS: Intervention arms included an electronic health record alert upon new opioid prescribing either alone or with one or both nudge interventions (written opioid justification and/or monthly clinician comparison emails).

MAIN OUTCOME MEASURES: We used conventional content and thematic analysis to identify themes related to clinician perceptions of nudge interventions and the opioid epidemic.

RESULTS: We conducted and analyzed 77 clinician interviews. Clinicians voiced favorable impressions of both nudge interventions, but they did not feel the nudge interventions had a direct impact on their own prescribing of opioids, perhaps due to low prescribing secondary to other opioid interventions. Clinicians felt interventions should continue to assist high opioid prescribers.

CONCLUSION: Nudge interventions are favorably perceived by physicians to be an additional option in the current landscape of interventions to prevent unsafe opioid prescribing for acute pain in the primary care setting.

2024

Park, Tae Woo, Tithi D Baul, Jake R Morgan, Timothy E Wilens, and Amy M Yule. (2024) 2024. “Trends in Attention-Deficit Hyperactivity Disorder Diagnosis and Pharmacotherapy Among Adults With Opioid Use Disorder.”. Psychiatric Services (Washington, D.C.) 75 (3): 214-20. https://doi.org/10.1176/appi.ps.20220400.

OBJECTIVE: This study aimed to assess nationwide trends in attention-deficit hyperactivity disorder (ADHD) diagnoses and pharmacotherapy among patients with opioid use disorder and ADHD and to examine factors predicting receipt of stimulant medications among patients receiving medications for opioid use disorder (MOUDs).

METHODS: A claims-based database of commercially insured patients ages 13-64 was used to conduct two analyses: an annual cross-sectional study of 387,980 patients diagnosed as having opioid use disorder (2007-2017) to estimate the prevalence of ADHD diagnoses and pharmacotherapy, and a retrospective cohort study of 158,591 patients receiving MOUDs to test, with multivariable regression, the association between patient characteristics and receipt of stimulant medication.

RESULTS: From 2007 to 2017, the prevalence of ADHD diagnoses increased from 4.6% to 15.1% and the rate of ADHD pharmacotherapy increased from 42.6% to 51.8% among patients with opioid use disorder. Among all patients receiving MOUDs, 10.5% received at least one prescription stimulant during the study period. Female sex; residence in the southern United States; and ADHD, mood, and anxiety disorder diagnoses were associated with increased likelihood of stimulant receipt. Stimulant use disorder and other substance use disorder diagnoses were associated with decreased likelihood of stimulant receipt.

CONCLUSIONS: ADHD diagnoses and pharmacotherapy among patients with opioid use disorder have increased. A minority of patients with ADHD and taking MOUDs received a stimulant. Further study is needed of the benefits and risks of ADHD pharmacotherapy for patients with opioid use disorder.

Xu, Kevin Young, Fábio A Nascimento, Binx Yezhe Lin, Tae Woo Park, Donovan T Maust, Hillary Samples, and Greta A Bushnell. (2024) 2024. “Benzodiazepine Receipt in Adults With Psychogenic Non-Epileptic Seizures in the USA.”. BMJ Neurology Open 6 (2): e000767. https://doi.org/10.1136/bmjno-2024-000767.

BACKGROUND: Characterising benzodiazepine (BZD) prescribing to individuals with psychogenic non-epileptic seizures (PNES) is important for optimising PNES outcomes, but existing data is lacking.

METHODS: Using a nationwide administrative claims database (2016-2022), incident PNES was defined as an International classification of diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis in an inpatient or outpatient healthcare encounter after a 1-year period with no documented diagnosis. We described clinical characteristics of adults with incident PNES and estimated the prevalence of outpatient BZD treatment in the baseline year and 30-day follow-up period, with secondary analyses stratifying by baseline ES, anxiety and/or insomnia diagnoses, representing common indications for BZD receipt. We used logistic regression to evaluate predictors of post-PNES BZD receipt.

RESULTS: Among 20 848 adults with incident PNES diagnosis, 33.1% and 15.1% received BZDs in the year and month prior to PNES diagnosis, respectively, and 18.1% received BZDs in the month following a PNES diagnosis; 5.4% of those without prior BZD prescriptions received BZDs after diagnosis. The median days' supply was 30 days, with clonazepam, alprazolam and lorazepam representing the most common BZDs prescribed after PNES. Most people who received BZDs in the month prior to PNES diagnosis remained on BZDs in the month after PNES diagnosis (62.9%), with similar findings in the subcohorts without ES, anxiety and/or insomnia. Baseline BZD receipt and anxiety disorders, but not baseline ES diagnoses, were strong independent predictors of post-PNES BZD receipt.

CONCLUSIONS: While new BZD initiation is rare after PNES, most individuals with BZD scripts 1 month before PNES continue scripts after diagnosis.

Drake, Coleman, Dylan Nagy, Mark K Meiselbach, Jane M Zhu, Brendan Saloner, Bradley D Stein, and Daniel Polsky. (2024) 2024. “Racial and Ethnic Disparities in Geographic Availability of Buprenorphine.”. Journal of Addiction Medicine 18 (3): 335-38. https://doi.org/10.1097/ADM.0000000000001287.

OBJECTIVES: Overdose mortality has risen most rapidly among racial and ethnic minority groups while buprenorphine prescribing has increased disproportionately in predominantly non-Hispanic White urban areas. To identify whether buprenorphine availability equitably meets the needs of diverse populations, we examined the differential geographic availability of buprenorphine in areas with greater concentrations of racial and ethnic minority groups.

METHODS: Using IQVIA longitudinal prescription data, IQVIA OneKey data, and Microsoft Bing Maps, we calculated 2 outcome measures across the continental United States: the number of buprenorphine prescribers per 1000 residents within a 30-minute drive of a ZIP code, and the number of buprenorphine prescriptions dispensed per capita at retail pharmacies among nearby buprenorphine prescribers. We then estimated differences in these outcomes by ZIP codes' racial and ethnic minority composition and rurality with t tests.

RESULTS: Buprenorphine prescribers per 1000 residents within a 30-minute drive decreased by 3.8 prescribers per 1000 residents in urban ZIP codes (95% confidence interval = -4.9 to -2.7) and 2.6 in rural ZIP codes (95% confidence interval = -3.0 to -2.2) whose populations consisted of ≥5% racial and ethnic minority groups. There were 45% to 55% fewer prescribers in urban areas and 62% to 79% fewer prescribers in rural areas as minority composition increased. Differences in dispensed buprenorphine per capita were similar but larger in magnitude.

CONCLUSIONS: Achieving more equitable buprenorphine access requires not only increasing the number of buprenorphine-prescribing clinicians; in urban areas with higher racial and ethnic minority group populations, it also requires efforts to promote greater buprenorphine prescribing among already prescribing clinicians.

Park, Tae Woo, Tithi D Baul, Jake R Morgan, Timothy E Wilens, and Amy M Yule. (2024) 2024. “Trends in Attention-Deficit Hyperactivity Disorder Diagnosis and Pharmacotherapy Among Adults With Opioid Use Disorder.”. Psychiatric Services (Washington, D.C.) 75 (3): 214-20. https://doi.org/10.1176/appi.ps.20220400.

OBJECTIVE: This study aimed to assess nationwide trends in attention-deficit hyperactivity disorder (ADHD) diagnoses and pharmacotherapy among patients with opioid use disorder and ADHD and to examine factors predicting receipt of stimulant medications among patients receiving medications for opioid use disorder (MOUDs).

METHODS: A claims-based database of commercially insured patients ages 13-64 was used to conduct two analyses: an annual cross-sectional study of 387,980 patients diagnosed as having opioid use disorder (2007-2017) to estimate the prevalence of ADHD diagnoses and pharmacotherapy, and a retrospective cohort study of 158,591 patients receiving MOUDs to test, with multivariable regression, the association between patient characteristics and receipt of stimulant medication.

RESULTS: From 2007 to 2017, the prevalence of ADHD diagnoses increased from 4.6% to 15.1% and the rate of ADHD pharmacotherapy increased from 42.6% to 51.8% among patients with opioid use disorder. Among all patients receiving MOUDs, 10.5% received at least one prescription stimulant during the study period. Female sex; residence in the southern United States; and ADHD, mood, and anxiety disorder diagnoses were associated with increased likelihood of stimulant receipt. Stimulant use disorder and other substance use disorder diagnoses were associated with decreased likelihood of stimulant receipt.

CONCLUSIONS: ADHD diagnoses and pharmacotherapy among patients with opioid use disorder have increased. A minority of patients with ADHD and taking MOUDs received a stimulant. Further study is needed of the benefits and risks of ADHD pharmacotherapy for patients with opioid use disorder.

Xu, Kevin Young, Fábio A Nascimento, Binx Yezhe Lin, Tae Woo Park, Donovan T Maust, Hillary Samples, and Greta A Bushnell. (2024) 2024. “Benzodiazepine Receipt in Adults With Psychogenic Non-Epileptic Seizures in the USA.”. BMJ Neurology Open 6 (2): e000767. https://doi.org/10.1136/bmjno-2024-000767.

BACKGROUND: Characterising benzodiazepine (BZD) prescribing to individuals with psychogenic non-epileptic seizures (PNES) is important for optimising PNES outcomes, but existing data is lacking.

METHODS: Using a nationwide administrative claims database (2016-2022), incident PNES was defined as an International classification of diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis in an inpatient or outpatient healthcare encounter after a 1-year period with no documented diagnosis. We described clinical characteristics of adults with incident PNES and estimated the prevalence of outpatient BZD treatment in the baseline year and 30-day follow-up period, with secondary analyses stratifying by baseline ES, anxiety and/or insomnia diagnoses, representing common indications for BZD receipt. We used logistic regression to evaluate predictors of post-PNES BZD receipt.

RESULTS: Among 20 848 adults with incident PNES diagnosis, 33.1% and 15.1% received BZDs in the year and month prior to PNES diagnosis, respectively, and 18.1% received BZDs in the month following a PNES diagnosis; 5.4% of those without prior BZD prescriptions received BZDs after diagnosis. The median days' supply was 30 days, with clonazepam, alprazolam and lorazepam representing the most common BZDs prescribed after PNES. Most people who received BZDs in the month prior to PNES diagnosis remained on BZDs in the month after PNES diagnosis (62.9%), with similar findings in the subcohorts without ES, anxiety and/or insomnia. Baseline BZD receipt and anxiety disorders, but not baseline ES diagnoses, were strong independent predictors of post-PNES BZD receipt.

CONCLUSIONS: While new BZD initiation is rare after PNES, most individuals with BZD scripts 1 month before PNES continue scripts after diagnosis.

Drake, Coleman, Dylan Nagy, Mark K Meiselbach, Jane M Zhu, Brendan Saloner, Bradley D Stein, and Daniel Polsky. (2024) 2024. “Racial and Ethnic Disparities in Geographic Availability of Buprenorphine.”. Journal of Addiction Medicine 18 (3): 335-38. https://doi.org/10.1097/ADM.0000000000001287.

OBJECTIVES: Overdose mortality has risen most rapidly among racial and ethnic minority groups while buprenorphine prescribing has increased disproportionately in predominantly non-Hispanic White urban areas. To identify whether buprenorphine availability equitably meets the needs of diverse populations, we examined the differential geographic availability of buprenorphine in areas with greater concentrations of racial and ethnic minority groups.

METHODS: Using IQVIA longitudinal prescription data, IQVIA OneKey data, and Microsoft Bing Maps, we calculated 2 outcome measures across the continental United States: the number of buprenorphine prescribers per 1000 residents within a 30-minute drive of a ZIP code, and the number of buprenorphine prescriptions dispensed per capita at retail pharmacies among nearby buprenorphine prescribers. We then estimated differences in these outcomes by ZIP codes' racial and ethnic minority composition and rurality with t tests.

RESULTS: Buprenorphine prescribers per 1000 residents within a 30-minute drive decreased by 3.8 prescribers per 1000 residents in urban ZIP codes (95% confidence interval = -4.9 to -2.7) and 2.6 in rural ZIP codes (95% confidence interval = -3.0 to -2.2) whose populations consisted of ≥5% racial and ethnic minority groups. There were 45% to 55% fewer prescribers in urban areas and 62% to 79% fewer prescribers in rural areas as minority composition increased. Differences in dispensed buprenorphine per capita were similar but larger in magnitude.

CONCLUSIONS: Achieving more equitable buprenorphine access requires not only increasing the number of buprenorphine-prescribing clinicians; in urban areas with higher racial and ethnic minority group populations, it also requires efforts to promote greater buprenorphine prescribing among already prescribing clinicians.