Publications

2019

Schleiden, Loren J, Carolyn T Thorpe, John P Cashy, Walid F Gellad, Chester B Good, Joseph T Hanlon, Maria K Mor, et al. (2019) 2019. “Characteristics of Dual Drug Benefit Use Among Veterans With Dementia Enrolled in the Veterans Health Administration and Medicare Part D.”. Research in Social & Administrative Pharmacy : RSAP 15 (6): 701-9. https://doi.org/10.1016/j.sapharm.2018.09.001.

BACKGROUND: Obtaining prescription medications from multiple health systems may complicate coordination of care. Older Veterans who obtain medications concurrently through Veterans Affairs (VA) benefits and Medicare Part D benefits (dual users) are at higher risk of unintended negative outcomes.

OBJECTIVE: To explore characteristics predicting dual drug benefit use from both VA and Medicare Part D in a national sample of older Veterans with dementia.

METHODS: Administrative data were obtained from the VA and Medicare for a national sample of 110,828 Veterans with dementia ages 68 and older in 2010. Veterans were classified into three drug benefit user groups based on the source of all prescription medications they obtained in 2010: VA-only, Part D-only, and Dual Use. Multinomial logistic regression was used to examine predictors of drug benefit user group. The source of prescriptions was described for each of the ten most frequently used drug classes and opioids.

RESULTS: Fifty-six percent of Veterans received all of their prescription medications from VA-only, 28% from Part D-only, and 16% from both VA and Part D. Veterans who were eligible for Medicaid or who had a priority group score conferring less generous drug benefits within the VA were more likely to be Part D-only or dual users. Nearly one fourth of Veterans taking opioids concurrently received opioid prescriptions from dual sources (24.7%).

CONCLUSIONS: Medicaid eligibility and Veteran priority group status, which largely decrease copayments for drugs obtained outside versus within the VA, respectively, were the main factors predicting drug user benefit group. Policies to encourage single-system prescribing and enhance communication across health systems are crucial to preventing negative health outcomes related to care fragmentation.

Cochran, Gerald, Evan S Cole, Jack Warwick, Julie M Donohue, Adam J Gordon, Walid F Gellad, Todd Bear, David Kelley, Ellen DiDomenico, and Jan Pringle. (2019) 2019. “Rural Access to MAT in Pennsylvania (RAMP): A Hybrid Implementation Study Protocol for Medication Assisted Treatment Adoption Among Rural Primary Care Providers.”. Addiction Science & Clinical Practice 14 (1): 25. https://doi.org/10.1186/s13722-019-0154-4.

BACKGROUND: The continued escalation of opioid use disorder (OUD) calls for heightened vigilance to implement evidence-based care across the US. Rural care providers and patients have limited resources, and a number of barriers exist that can impede necessary OUD treatment services. This paper reports the design and protocol of an implementation study seeking to advance availability of medication assisted treatment (MAT) for OUD in rural Pennsylvania counties for patients insured by Medicaid in primary care settings.

METHODS: This project was a hybrid implementation study. Within a chronic care model paradigm, we employed the Framework for Systems Transformation to implement the American Society for Addiction Medicine care model for the use of medications in the treatment of OUD. In partnership with state leadership, Medicaid managed care organizations, local care management professionals, the Universities of Pittsburgh and Utah, primary care providers (PCP), and patients; the project team worked within 23 rural Pennsylvania counties to engage, recruit, train, and collaborate to implement the OUD service model in PCP practices from 2016 to 2019. Formative measures included practice-level metrics to monitor project implementation, and outcome measures involved employing Medicaid claims and encounter data to assess changes in provider/patient-level OUD-related metrics, such as MAT provider supply, prevalence of OUD, and MAT utilization. Descriptive statistics and repeated measures regression analyses were used to assess changes across the study period.

DISCUSSION: There is an urgent need in the US to expand access to high quality, evidence-based OUD treatment-particularly in rural areas where capacity is limited for service delivery in order to improve patient health and protect lives. Importantly, this project leverages multiple partners to implement a theory- and practice-driven model of care for OUD. Results of this study will provide needed evidence in the field for appropriate methods for implementing MAT among a large number of rural primary care providers.

Metes, Ilinca D, Lingshu Xue, Chung-Chou H Chang, Haiden A Huskamp, Walid F Gellad, Wei-Hsuan Lo-Ciganic, Niteesh K Choudhry, Seth Richards-Shubik, Hasan Guclu, and Julie M Donohue. (2019) 2019. “Association Between Physician Adoption of a New Oral Anti-Diabetic Medication and Medicare and Medicaid Drug Spending.”. BMC Health Services Research 19 (1): 703. https://doi.org/10.1186/s12913-019-4520-4.

BACKGROUND: In the United States, there is well-documented regional variation in prescription drug spending. However, the specific role of physician adoption of brand name drugs on the variation in patient-level prescription drug spending is still being investigated across a multitude of drug classes. Our study aims to add to the literature by determining the association between physician adoption of a first-in-class anti-diabetic (AD) drug, sitagliptin, and AD drug spending in the Medicare and Medicaid populations in Pennsylvania.

METHODS: We obtained physician-level data from QuintilesIMS Xponent™ database for Pennsylvania and constructed county-level measures of time to adoption and share of physicians adopting sitagliptin in its first year post-introduction. We additionally measured total AD drug spending for all Medicare fee-for-service and Part D enrollees (N = 125,264) and all Medicaid (N = 50,836) enrollees with type II diabetes in Pennsylvania for 2011. Finite mixture model regression, adjusting for patient socio-demographic/clinical characteristics, was used to examine the association between physician adoption of sitagliptin and AD drug spending.

RESULTS: Physician adoption of sitagliptin varied from 44 to 99% across the state's 67 counties. Average per capita AD spending was $1340 (SD $1764) in Medicare and $1291 (SD $1881) in Medicaid. A 10% increase in the share of physicians adopting sitagliptin in a county was associated with a 3.5% (95% CI: 2.0-4.9) and 5.3% (95% CI: 0.3-10.3) increase in drug spending for the Medicare and Medicaid populations, respectively.

CONCLUSIONS: In a medication market with many choices, county-level adoption of sitagliptin was positively associated with AD spending in Medicare and Medicaid, two programs with different approaches to formulary management.

Cole, Evan S, Ellen DiDomenico, Gerald Cochran, Adam J Gordon, Walid F Gellad, Janice Pringle, Jack Warwick, et al. (2019) 2019. “The Role of Primary Care in Improving Access to Medication-Assisted Treatment for Rural Medicaid Enrollees With Opioid Use Disorder.”. Journal of General Internal Medicine 34 (6): 936-43. https://doi.org/10.1007/s11606-019-04943-6.

BACKGROUND: The opioid epidemic has disproportionately affected rural areas, where a limited number of health care providers offer medication-assisted treatment (MAT), the mainstay of treatment for opioid use disorder (OUD). Rural residents with OUD may face multiple barriers to engagement in MAT including long travel distances.

OBJECTIVE: To examine the degree to which rural residents with OUD are engaged with primary care providers (PCPs), describe the role of rural PCPs in MAT delivery, and estimate the association between enrollee distance to MAT prescribers and MAT utilization.

DESIGN: Retrospective cohort study.

PARTICIPANTS: Medicaid-enrolled adults diagnosed with OUD in 23 rural Pennsylvania counties.

MAIN MEASURES: Primary care utilization, MAT utilization, distance to nearest possible MAT prescriber, mean distance traveled to actual MAT prescribers, and continuity of pharmacotherapy.

KEY RESULTS: Of the 7930 Medicaid enrollees with a diagnosis of OUD, a minority (18.6%) received their diagnosis during a PCP visit even though enrollees with OUD had 4.1 visits to PCPs per person-year in 2015. Among enrollees with an OUD diagnosis recorded during a PCP visit, about half (751, 50.8%) received MAT, most of whom (508, 67.6%) received MAT from a PCP. Enrollees with OUD with at least one PCP visit were more likely than those without a PCP visit to receive MAT (32.7% vs. 25%; p < 0.001), and filled more buprenorphine and naltrexone prescriptions (mean = 11.1 vs. 9.3; p < 0.001). The median of the distances traveled to actual MAT prescribers was 48.8 miles, compared to a median of 4.2 miles to the nearest available MAT prescriber. Enrollees traveling a mean distance greater than 45 miles to MAT prescribers were less likely to receive continuity of pharmacotherapy (OR = 0.71, 95% CI = 0.56-0.91, p = 0.007).

CONCLUSIONS: PCP utilization among rural Medicaid enrollees diagnosed with OUD is high, presenting a potential intervention point to treat OUD, particularly if the enrollee's PCP is located nearer than their MAT prescriber.

Thorpe, Joshua M, Carolyn T Thorpe, Loren Schleiden, John Cashy, Ronald Carico, Walid F Gellad, and Courtney Harold Van Houtven. (2019) 2019. “Association Between Dual Use of Department of Veterans Affairs and Medicare Part D Drug Benefits and Potentially Unsafe Prescribing.”. JAMA Internal Medicine 179 (11): 1584-86. https://doi.org/10.1001/jamainternmed.2019.2788.

This observational study evaluates the association of dual prescribing for Veterans Affairs and Medicare Part D benefits with unsafe prescription exposure in a national cohort of older veterans.

2018

Newberry, Carolyn, Ravy K Vajravelu, Octavia Pickett-Blakely, Gary Falk, Yu Xiao Yang, and Kristle L Lynch. (2018) 2018. “Achalasia Patients Are at Nutritional Risk Regardless of Presenting Weight Category.”. Digestive Diseases and Sciences 63 (5): 1243-49. https://doi.org/10.1007/s10620-018-4985-8.

BACKGROUND: Achalasia is an esophageal motor disorder that leads to swallowing dysfunction and weight loss. Nutritional risk in achalasia patients is not well defined.

AIMS: The aims of this study were to define baseline body mass index (BMI), changes in weight, and nutritional risk over time in a large cohort of achalasia patients.

METHODS: This was a retrospective cohort study of achalasia patients at a tertiary care center with documented BMI, symptom severity as per Eckardt score, and nutritional risk assessment as per the Malnutrition Universal Screening Tool, which considers BMI, degree of recent weight loss, and acuity of disease.

RESULTS: Among the 337 patients presenting for achalasia management, 179 had confirmed disease. Upon presentation 69.8% of patients were classified as overweight or obese. Using the Malnutrition Universal Screening Tool, we found 50% of patients to be at moderate or high risk for malnutrition at presentation. Eckardt score (OR 1.15, 95% CI 1.05-1.26), duration of disease (OR for each additional month 1.04, 95% CI 1.01-1.08), and female gender (OR 1.76, 95% CI 1.02-3.03) were independent predictors of increased risk for malnutrition. Nutrition risk score decreased after therapy in 93.3% of patients.

CONCLUSIONS: Despite a high prevalence of overweight and obese status in achalasia patients, many are at risk of developing nutritional complications secondary to rapid weight loss. This risk frequently resolves post-treatment. Regardless of baseline BMI, we recommend all patients undergo nutritional assessment to identify high-risk patients who may benefit from dietary intervention and expedited therapy.

Papamichael, Konstantinos, Ravy K Vajravelu, Mark T Osterman, and Adam S Cheifetz. (2018) 2018. “Long-Term Outcome of Infliximab Optimization for Overcoming Immunogenicity in Patients With Inflammatory Bowel Disease.”. Digestive Diseases and Sciences 63 (3): 761-67. https://doi.org/10.1007/s10620-018-4917-7.

BACKGROUND: Preliminary data suggest that treatment optimization can reverse immunogenicity and regain response in patients with IBD and secondary loss of response (SLR) to anti-TNF therapy due to antidrug antibodies. However, data regarding the long-term outcome of these patients are scarce.

AIMS: We aimed to investigate drug retention in IBD patients of whom infliximab was optimized to overcome immunogenicity and variables associated with drug retention.

METHODS: This was a retrospective, multicenter study of consecutive IBD patients with antibodies to infliximab (ATI), based on either proactive or reactive therapeutic drug monitoring, who underwent infliximab optimization (increasing dose, shortening interval, adding an immunomodulator, or combination) to overcome immunogenicity from September 2012 to July 2015; they were followed through December 2015. ATI were analyzed using the drug-tolerant Prometheus homogeneous mobility shift assay. Drug retention was defined as no need for drug discontinuation due to SLR or serious adverse event.

RESULTS: Our cohort consisted of 22 patients (Crohn's disease, n = 15). At the end of follow-up [median, (IQR): 17.3 (10.5-32.8) months] 77% (15/22) of patients were still on drug. Univariable Cox proportional hazards regression analysis identified first detectable ATI titer as the only variable associated with drug retention (HR: 0.89; 95% CI: 0.82-0.98, p = 0.016). Receiver-operating characteristic analysis identified an ATI titer < 8.8 U/mL associated with drug retention.

CONCLUSIONS: In real-life clinical practice, optimization of infliximab therapy can prevent drug discontinuation in approximately 3/4 of patients with ATI, especially in those with low titers. Large prospective studies are needed to confirm these data.

Osterman, Chelsea K, Jaber Alanzi, James D Lewis, Elizabeth L Kaufman, Vivek Narayan, Ben Boursi, Ravy K Vajravelu, Frank I Scott, Bruce Malkowicz, and Ronac Mamtani. (2018) 2018. “Association Between Symptomatic Versus Asymptomatic Recurrence and Survival in Bladder Cancer.”. Clinical Genitourinary Cancer 16 (3): 235-39. https://doi.org/10.1016/j.clgc.2017.11.001.

BACKGROUND: The benefit of surveillance after curative cystectomy in bladder cancer is unproven, but might be justified if detection of asymptomatic recurrence improves survival. Previous studies showing a benefit of surveillance might have been affected by lead-time or length-time bias.

MATERIALS AND METHODS: We conducted a retrospective cohort study among 463 cystectomy patients at the University of Pennsylvania. Patients were followed according to a standardized protocol and classified according to asymptomatic or symptomatic recurrence detection. Primary outcome was all-cause mortality. Adjusted Cox regression models were used to assess the effect of mode of recurrence on survival from time of cystectomy (model 1) and time of recurrence (model 2) to account for lead and length time.

RESULTS: One hundred ninety-seven patients (42.5%) recurred; 71 were asymptomatic (36.0%), 107 were symptomatic (54.3%), and 19 (9.6%) were unknown. Relative to patients with asymptomatic recurrence, patients with symptomatic recurrence had significantly increased risk of death (model 1: hazard ratio [HR], 1.67; 95% confidence interval [CI], 1.07-2.61; model 2: HR, 1.74, 95% CI, 1.13-2.69) and had lower 1-year overall survival from time of recurrence (29.37% vs. 55.66%). Symptomatic patients were diagnosed with recurrence a median of 1.7 months before asymptomatic patients, yet their median survival from recurrence was 8.2 months less.

CONCLUSION: Symptomatic recurrence is associated with worse outcomes than asymptomatic recurrence, which cannot be explained by lead- or length-time bias. Similar methods to account for these biases should be considered in studies of cancer surveillance. Shortening surveillance intervals might allow for detection of more recurrences in an asymptomatic phase.

Vajravelu, Ravy K, Ronac Mamtani, Frank I Scott, Adam Waxman, and James D Lewis. (2018) 2018. “Incidence, Risk Factors, and Clinical Effects of Recurrent Diverticular Hemorrhage: A Large Cohort Study.”. Gastroenterology 155 (5): 1416-27. https://doi.org/10.1053/j.gastro.2018.07.026.

BACKGROUND & AIMS: Although recurrent diverticular hemorrhage is common, its incidence and risk factors have not been measured outside of small institutional cohorts. We analyzed the incidence of and risk factors for recurrent diverticular hemorrhage and whether discontinuing anticoagulation after diverticular hemorrhage is associated with ischemic stroke.

METHODS: We performed a retrospective cohort study of patients enrolled in the OptumInsight Clinformatics database from 2000 through 2016. Incidence rates for initial and recurrent diverticular hemorrhage were calculated by identifying patients who had hospitalizations with a primary discharge diagnosis consistent with diverticular hemorrhage. The hazard ratios of second diverticular hemorrhage associated with anticoagulants or platelet aggregation inhibitors were calculated using Cox proportional hazards regression adjusted for demographics, comorbidities, and medication use. The hazard ratio for ischemic stroke among patients who discontinued anticoagulation after diverticular hemorrhage was calculated similarly.

RESULTS: In the cohort analyzed, 14,925 patients had an initial diverticular hemorrhage; 1368 of these patients had a second episode. The unstandardized incidence rates of initial and second diverticular hemorrhage were 10.9 per 100,000 person-years (95% confidence interval [CI] 10.7-11.0) and 3625.6 per 100,000 person-years (95% CI 3436.0-3823.0). Platelet aggregation inhibitors were associated with second episodes of diverticular hemorrhage (hazard ratio 1.47; 95% CI 1.15-1.88), whereas all classes of anticoagulation agents were not associated. Among patients with a potential indication for stroke prophylaxis, those who discontinued anticoagulation after the diverticular hemorrhage had an increased hazard of ischemic stroke (hazard ratio 1.93; 95% CI 1.17-3.19).

CONCLUSIONS: In this retrospective cohort study, platelet aggregation inhibitors, but not anticoagulants, were associated with recurrent diverticular hemorrhage. Discontinuing anticoagulation was associated with increased hazard for ischemic stroke.