Publications

BACKGROUND: Many Veterans treated within the VA Healthcare System (VA) are also enrolled in fee-for-service (FFS) Medicare and receive treatment outside the VA. Prior research has not accounted for the multiple ways that Veterans receive services across healthcare systems.

OBJECTIVE: We aimed to establish a typology of VA and Medicare utilization among dually enrolled Veterans with type 2 diabetes.

DESIGN: This was a retrospective cohort.

PARTICIPANTS: 316,775 community-dwelling Veterans age ≥ 65 years with type 2 diabetes who were dually enrolled in the VA and FFS Medicare in 2008-2009.

METHODS: Using latent class analysis, we identified classes of Veterans based upon their probability of using VA and Medicare diabetes care services, including patient visits, laboratory tests, glucose test strips, and medications. We compared the amount of healthcare use between classes and identified factors associated with class membership using multinomial regression.

KEY RESULTS: We identified four distinct latent classes: class 1 (53.9%) had high probabilities of VA use and low probabilities of Medicare use; classes 2 (17.2%), 3 (21.8%), and 4 (7.0%) had high probabilities of VA and Medicare use, but differed in their Medicare services used. For example, Veterans in class 3 received test strips exclusively through Medicare, while Veterans in class 4 were reliant on Medicare for medications. Living ≥ 40 miles from a VA predicted membership in classes 3 (OR 1.1, CI 1.06-1.15) and 4 (OR 1.11, CI 1.04-1.18), while Medicaid eligibility predicted membership in class 4 (OR 4.30, CI 4.10-4.51).

CONCLUSIONS: Veterans with diabetes can be grouped into four distinct classes of dual health system use, representing a novel way to characterize how patients use multiple services across healthcare systems. This classification has applications for identifying patients facing differential risk from care fragmentation.

BACKGROUND: Variation in physician adoption of new medications is poorly understood. Traditional approaches (eg, measuring time to first prescription) may mask substantial heterogeneity in technology adoption.

OBJECTIVE: Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant.

METHODS: A retrospective cohort study using prescribing data from IMS Xponent™ on all Pennsylvania physicians regularly prescribing anticoagulants (n=3911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription and group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions.

OUTCOMES: Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran.

RESULTS: We identified 5 distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in ≤3 mo with 45% of prescriptions) and 13.4% were rapid and moderate adopters (≤3 mo with 20% share). Two groups accounting for 21.6% and 16.1% of physicians, respectively, were slower to adopt (6-10 mo post-introduction) and dabigatran accounted for <10% share. Nearly half (45.2%) of anticoagulant prescribers did not adopt dabigatran. Cardiologists were much more likely than primary care physicians to rapidly adopt [odds ratio (OR)=12.2; 95% confidence interval (CI), 9.27-16.1] as were younger prescribers (age 36-45 y: OR=1.49, 95% CI, 1.13-1.95; age 46-55: OR=1.34, 95% CI, 1.07-1.69 vs. >55 y).

CONCLUSIONS: Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment.

BACKGROUND AND AIMS: Uncertainty about optimal treatment duration for buprenorphine opioid agonist therapy may lead to substantial variation in provider and payer decision-making regarding treatment course. We aimed to identify distinct trajectories of buprenorphine use and examine outcomes associated with these trajectories to guide health system interventions regarding treatment length.

DESIGN: Retrospective cohort study.

SETTING: US Pennsylvania Medicaid.

PATIENTS: A total of 10 945 enrollees aged 18-64 years initiating buprenorphine treatment between 2007 and 2012.

MEASUREMENTS: Group-based trajectory models were used to identify trajectories based on monthly proportion of days covered with buprenorphine in the 12 months post-treatment initiation. We used separate multivariable Cox proportional hazard models to examine associations between trajectories and time to first all-cause hospitalization and emergency department (ED) visit within 12 months after the first-year treatment.

FINDINGS: Six trajectories [Bayesian information criterion (BIC) = -86 246.70] were identified: 24.9% discontinued buprenorphine < 3 months, 18.7% discontinued between 3 and 5 months, 12.4% discontinued between 5 and 8 months, 13.3% discontinued > 8 months, 9.5% refilled intermittently and 21.2% refilled persistently for 12 months. Persistent refill trajectories were associated with an 18% lower risk of all-cause hospitalizations [hazard ratio (HR) = 0.82, 95% confidence interval (CI) = 0.70-0.95] and 14% lower risk of ED visits (HR = 0.86, 95% CI = 0.78-0.95) in the subsequent year, compared with those discontinuing between 3 and 5 months.

CONCLUSIONS: Six distinct buprenorphine treatment trajectories were identified in this population-based low-income Medicaid cohort in Pennsylvania, USA. There appears to be an association between persistent use of buprenorphine for 12 months and lower risk of all-cause hospitalizations/emergency department visits.

In August 2015, the US Food and Drug Administration (FDA) made the controversial decision to approve flibanserin (Addyi®) for women experiencing hypoactive sexual desire disorder. A number of factors contributed to disagreements regarding the FDA's decision, including the product's two prior failed FDA reviews, the unmet need of women with this disorder, extensive advocacy and politicization surrounding the product's relevance to women and sexual health, the potential for widespread off-label use, and the product's tenuous risk/benefit profile. Despite that, attention now shifts to maximizing the safe use of the product, including the optimal means to avoid numerous drug-drug interactions as well as the concomitant use of alcohol, both of which potentiate the risks of dizziness, hypotension, and syncope. Although the FDA has implemented a comprehensive Risk Evaluation and Mitigation Strategies program to maximize the product's safe use, patients, clinicians, and regulators must exhibit heightened vigilance early in the product's post-market life.

BACKGROUND: Medications to treat and prevent chronic disease have substantially reduced morbidity and mortality; however, their diffusion has been uneven. Little is known about prescribing of chronic disease medications by nurse practitioners (NPs) and physician assistants (PAs), despite their increasingly important role as primary care providers. Thus, we sought to conduct an exploratory analysis to examine prescribing of new chronic disease medications by NPs and PAs compared to primary care physicians (PCPs).

METHODS: We obtained prescribing data from IMS Health's Xponent™ on all NPs, PAs, and PCPs in Pennsylvania regularly prescribing anticoagulants, antihypertensives, oral hypoglycemics, and/or HMG-Co-A reductase inhibitors pre- and post-introduction of five new drugs in these classes that varied in novelty (i.e., dabigatran, aliskiren, sitagliptin or saxagliptin, and pitavastatin). We constructed three measures of prescriber adoption during the 15-month post-FDA approval period: 1) any prescription of the medication, 2) proportion of prescriptions in the class for the medication, and 3) time to adoption (first prescription) of the medication.

RESULTS: From 2007 to 2011, the proportion of antihypertensive prescriptions prescribed by NPs and PAs approximately doubled from 2.0 to 4.2 % and 2.2 to 4.9 %, respectively. Similar trends were found for anticoagulants, oral hypoglycemics, and HMG-Co-A reductase inhibitors. By 2011, more PCPs had prescribed each of the newly approved medications than NPs and PAs (e.g., 44.3 % vs. 18.5 % vs. 20 % for dabigatran among PCPs, NPs, and PAs). Across all medication classes, the newly approved drugs accounted for a larger share of prescriptions in the class for PCPs followed by PAs, followed by NPs (e.g., dabigatran: 4.9 % vs. 3.2 % vs. 2.8 %, respectively). Mean time-to-adoption for the newly approved medications was shorter for PCPs compared to NPs and PAs (e.g., dabigatran, 7.3 vs. 8.2 vs. 8.5 months; P all medications <0.001).

CONCLUSIONS: PCPs were more likely to prescribe each of the newly approved medications per each measure of drug adoption, regardless of drug novelty. Differences in the rate and speed of drug adoption between PCPs, NPs, and PAs may have important implications for care and overall costs at the population level as NPs and PAs continue taking on a larger role in prescribing.

BACKGROUND/OBJECTIVE: We have previously shown that an extracellular matrix (ECM) bioscaffold derived from porcine small intestine submucosa (SIS) enhanced the healing of a gap injury of the medial collateral ligament as well as the central third defect of the patellar tendon. With the addition of a hydrogel form of SIS, we found that a transected goat anterior cruciate ligament (ACL) could also be healed. The result begs the research question of whether SIS hydrogel has positive effects on ACL fibroblasts (ACLFs) and thus facilitates ACL healing.

METHODS: In the study, ECM-SIS hydrogel was fabricated from the digestion of decellularised and sterilised sheets of SIS derived from αGal-deficient (GalSafe) pigs. As a comparison, a pure collagen hydrogel was also fabricated from commercial collagen type I solution. The morphometrics of hydrogels was assessed with scanning electron microscopy. The ECM-SIS and collagen hydrogels had similar fibre diameters (0.105 ± 0.010 μm vs. 0.114 ± 0.004 μm), fibre orientation (0.51 ± 0.02 vs. 0.52 ± 0.02), and pore size (0.092 ± 0.012 μm vs. 0.087 ± 0.008 μm). The preservation of bioactive properties of SIS hydrogel was assessed by detecting bioactive molecules sensitive to processing and enzyme digestion, such as growth factors fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta 1 (TGF-β1), with enzyme-linked immunosorbent assay. ACLFs were isolated and expanded in culture from explants of rat ACLs (n = 3). The cells were then seeded on the hydrogels and cultured with 0%, 1%, and 10% foetal bovine serum (FBS) for 3 days and 7 days. Cell attachment was observed using a light microscope and scanning electron microscopy, whereas cell proliferation and matrix production (collagen types I and III) were examined with bromodeoxyuridine assays and reverse transcription-polymerase chain reaction, respectively.

RESULTS: The results showed that FGF-2 and TGF-β1 in the SIS hydrogel were preserved by 50% (65.9 ± 26.1 ng/g dry SIS) and 90% (4.4 ± 0.6 ng/g dry SIS) relative to their contents in ECM-SIS sheets, respectively. At Day 3 of culture, ACLFs on the SIS hydrogel were found to proliferate 39%, 31%, and 22% more than those on the pure collagen hydrogel at 0%, 1%, and 10% FBS, respectively (p < 0.05). Collagen type I mRNA expression was increased by 150%, 207%, and 100%, respectively, compared to collagen hydrogel (p < 0.05), whereas collagen type III mRNA expression was increased by 123% and 132% at 0% and 1% FBS, respectively (all p < 0.05) but not at 10% FBS. By Day 7, collagen type I mRNA expression was still elevated by 137% and 100% compared to collagen hydrogel at 1% and 10% FBS, respectively (p < 0.05). Yet, collagen type III mRNA levels were not significantly different between the two groups at any FBS concentrations.

CONCLUSION: Our data showed that the ECM-SIS hydrogel not only supported the growth of ACLFs, but also promoted their proliferation and matrix production relative to a pure collagen hydrogel. As such, ECM-SIS hydrogel has potential therapeutic value to facilitate ACL healing at the early stage after injury.

BACKGROUND & AIMS: Combination therapy with infliximab and azathioprine has demonstrated benefit over monotherapy for moderate-to-severe Crohn's disease. Clinical trials and models have not accounted for age-specific risks associated with these therapies, including the risk of immunosuppression-related cancer and infection. After accounting for these risks, the strategy yielding the greatest benefit may vary with age.

METHODS: We assessed age-specific risks and benefits of combination therapy compared with infliximab monotherapy by using Markov modeling. The base case was a 35-year-old male patient with a 1-year time horizon. We assumed the incidence of lymphoma to be 5.28-fold higher with combination therapy. Secondary analyses accounted for life expectancy, therapy beyond 1 year, and age-specific surgical and infection risks. Quality-adjusted life years (QALYs) were calculated for 25- to 75-year old individuals.

RESULTS: Combination therapy was found to be of greater benefit in the base case (0.7522 QALYs for combination therapy vs 0.7426 QALYs for monotherapy). Accounting for life years lost, monotherapy was the best approach if the hazard ratio for lymphoma with combination therapy was >8.1 patients who were 75 years old. Monotherapy provided greater net benefit to patients 55, 65, or 75 years old if therapy was extended for 9, 7, or 5 years, respectively. For 25-year-old men, monotherapy resulted in fewer deaths but only yielded greater QALYs if the annual incidence of hepatosplenic T-cell lymphoma exceeded 36/100,000 persons.

CONCLUSIONS: After accounting for age-specific risks of lymphoma, infection, and surgical complications, benefits of combination therapy outweighed the risks as a short-term and intermediate-term strategy for most patients with moderate-to-severe Crohn's disease who were younger than 65 years. For young male patients, combination therapy yields greater QALYs but at cost of an increased risk of death from lymphoma.