Interprofessional transformation of clinical education: The first six years of the Veterans Affairs Centers of Excellence in Primary Care Education.

This paper describes the Centers of Excellence in Primary Care Education (CoEPCE), a seven-site collaborative project funded by the Office of Academic Affiliations (OAA) within the Veterans Health Administration of the United States Department of Veterans Affairs (VA). The CoEPCE was established to fulfill OAA's vision of large-scale transformation of the clinical learning environment within VA primary care settings. This was accomplished by funding new Centers within VA facilities to develop models of interprofessional education (IPE) to teach health professions trainees to deliver high quality interprofessional team-based primary care to Veterans. Using reports and data collected and maintained by the National Coordinating Center over the first six years of the project, we describe program inputs, the multicomponent intervention, activities undertaken to develop the intervention, and short-term outcomes. The findings have implications for lessons learned that can be considered by others seeking large-scale transformation of education within the clinical workplace and the development of interprofessional clinical learning environments. Within the VA, the CoEPCE has laid the foundation for IPE and collaborative practice, but much work remains to disseminate this work throughout the national VA system.

Comparative treatment effectiveness of direct acting antiviral regimens for hepatitis C: Data from the Veterans administration.

BACKGROUND AND AIMS: Data addressing real world effectiveness of direct acting antiviral agents in hepatitis C infected patients are now emerging. This study compared the sustained virologic response rates achieved 12 weeks post-treatment in patients treated with three such agents by the Veterans Health Administration. METHODS: A retrospective cohort study was conducted using patients who terminated treatment by July 1, 2015. Data were retrieved from the Veterans Health Administration electronic medical records system. Patients were included if sufficient viral load laboratory data were available to determine sustained virologic response. Applying an intention to treat approach and logistic regression analysis, the sustained virologic response rates achieved were compared across drug regimens. RESULTS: A total of 11 464 patients met study selection criteria. Without controlling for other risk factors, sustained virologic response at least 12 weeks post treatment was achieved in 92% of ledipasvir/ sofosbuvir, 86% of ombitasvir/paritaprevir/ritonavir/dasabuvir, and 83% of simeprevir/sofosbuvir patients. After adjusting for patient characteristics, simeprevir/sofosbuvir (93.3%) and ledipasvir/sofosbuvir (96.2%) patients were statistically more likely than ombitasvir/paritaprevir/ritonavir/dasabuvir (91.8%) patients to demonstrate sustained virologic response. Human immunodeficiency virus, hepatitis B infection, diabetes, obesity, previous treatment history and augmentation therapy using ribavirin did not impact sustained virologic response rates. Sustained virologic response rates were lower for patients under age 65, with cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, indications of fibrosis, or a non-genotype 1 infection. Women and Caucasian patients were more likely to achieve a sustained virologic response. CONCLUSIONS: All three direct acting antiviral regimens appear highly effective in achieving sustained virologic response.

Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.

BACKGROUND: Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS). METHODS: Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations. RESULTS: 5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS. CONCLUSION: Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.

The clinical and economic burdens of metabolic dysfunction-associated steatohepatitis.

AIMS: This study aimed to assess and compare the health care resource utilization (HCRU) and medical cost of metabolic dysfunction-associated steatohepatitis (MASH) by disease severity based on Fibrosis-4 Index (FIB-4) score among US adults in a real-world setting. MATERIALS AND METHODS: This observational cohort study used claims data from the Healthcare Integrated Research Database (HIRD) to compare all-cause, cardiovascular (CV)-related, and liver-related HCRU, including hospitalization, and medical costs stratified by FIB-4 score among patients with MASH (identified by International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] code K75.81). Hospitalization and medical costs were compared by FIB-4 score using generalized linear regression with negative binomial and gamma distribution models, respectively, while controlling for confounders. RESULTS: The cohort included a total of 5,104 patients with MASH and comprised 3,162, 1,343, and 599 patients with low, indeterminate, and high FIB-4 scores, respectively. All-cause hospitalization was significantly higher in the high FIB-4 cohort when compared with the low FIB-4 reference after covariate adjustment (rate ratio, 1.63; 95% CI, 1.32-2.02; p < .0001). CV-related hospitalization was similar across all cohorts; however, CV-related costs were 1.26 times higher (95% CI, 1.11-1.45; p < .001) in the indeterminate cohort and 2.15 times higher (95% CI, 1.77-2.62; p < .0001) in the high FIB-4 cohort when compared with the low FIB-4 cohort. Patients with indeterminate and high FIB-4 scores had 2.97 (95% CI, 1.78-4.95) and 12.08 (95% CI, 7.35-19.88) times the rate of liver-related hospitalization and were 3.68 (95% CI, 3.11-4.34) and 33.73 (95% CI, 27.39-41.55) times more likely to incur liver-related costs, respectively (p < .0001 for all). LIMITATIONS: This claims-based analysis relied on diagnostic coding accuracy, which may not capture the presence of all diseases or all care received. CONCLUSIONS: High and indeterminate FIB-4 scores were associated with significantly higher liver-related clinical and economic burdens than low FIB-4 scores among patients with MASH.

MASH is a serious liver disease that can lead to fibrosis, cirrhosis, and other complications. There is a need to understand the impact of disease severity on the burden of MASH. Health care claims data were used to assess the use of medical resources, including hospitalization, and medical costs among patients with 3 different levels of severity of MASH, as assessed via FIB-4 score. FIB-4 is a widely available non-invasive marker of severity. Rates of all-cause, cardiovascular-related and liver-related hospitalization and medical costs were several-fold higher in patients with high disease severity of MASH than those with low disease severity of MASH.

Improvement of guideline ß-blocker prescribing in heart failure: a cluster-randomized pragmatic trial of a pharmacy intervention.

BACKGROUND: Treatment with specific beta-blockers and doses recommended by guidelines is often not achieved in practice. We evaluated an intervention directed to the pharmacy to improve prescribing. METHODS AND RESULTS: We conducted a pragmatic cluster-randomized trial, where facilities (n = 12) with patients (n = 220) were the clusters. Eligible patients had a beta-blocker prescription that was not guideline concordant. Level 1 intervention included information to a pharmacist on facility guideline concordance. Level 2 also provided a list of patients not meeting guideline goals. Intervention and follow-up periods were each 6 months. Achievement of full concordance with recommendations was low (4%-5%) in both groups, primarily due to lack of tolerability. However, compared with level 1, the level 2 intervention was associated with 1.9-fold greater odds of improvement in prescribing (95% confidence interval [CI] 1.1-3.2). Level 2 patients also had greater odds of a higher dose (1.9, 95% CI 1.1-3.3). The intervention was aided by the patient lists provided, the electronic medical record system, and staff support. CONCLUSIONS: In actual practice, full achievement of guideline goals was low. However, a simple intervention targeting pharmacy moved patients toward guideline goals. As health care systems incorporate electronic medical records, this intervention should have broader feasibility.

Impact of pharmacist-managed erythropoiesis-stimulating agents clinics for patients with non-dialysis-dependent CKD.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are associated with serious adverse events, and maintaining hemoglobin levels within a narrow range can be difficult. We examined the quality of ESA prescribing and monitoring in pharmacist-managed ESA clinics versus usual care in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). STUDY DESIGN: Historical cohort. SETTING & PARTICIPANTS: Outpatients receiving ESAs for NDD-CKD at 10 Veterans Affairs Medical Centers with both pharmacist-managed ESA clinics (n = 314) and physician-based care (ie, usual care; n = 91) and 6 sites with usual care only (n = 167) on January 1, 2009, were followed up for 6 months. PREDICTOR: Type/site of care (ie, pharmacist-managed ESA clinic, usual care at ESA clinic site, usual-care site). OUTCOMES: Primary outcomes were proportion of hemoglobin values in the target range of 10-12 g/dL, ESA dose, and frequency of hemoglobin monitoring. Factors associated with hemoglobin values out of target range were identified using multinomial logistic regression. RESULTS: More hemoglobin values were in the target range in pharmacist-managed ESA clinics (71.1% vs 56.9% for usual-care sites; P < 0.001). The average 30-day dose of darbepoetin was 163 µg in pharmacist-managed ESA clinic patients versus 240 µg in usual-care site patients and 258 µg in usual-care patients at ESA clinic sites. For epoetin, corresponding average 30-day doses were 44,890 versus 47,141 and 57,436 IU. Veterans in pharmacist-managed ESA clinics had more hemoglobin measurements on average (5.8 vs 3.6 in usual-care sites and 3.8 in usual care at ESA clinic sites; P = 0.007). In the multinomial model, usual care was associated with hemoglobin levels out of target range, whereas heart failure and diabetes were associated with values in range. LIMITATIONS: We could not assess whether different hemoglobin targets were used by usual-care providers. CONCLUSIONS: Relative to usual care, pharmacist-managed clinics provided improved quality of ESA dosing and monitoring for patients with NDD-CKD.

Comparative Effectiveness of Roflumilast and Azithromycin for the Treatment of Chronic Obstructive Pulmonary Disease.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) patients with exacerbations despite optimized bronchodilator therapy, roflumilast and chronic azithromycin are recommended options. Roflumilast is recommended in severe COPD patients with chronic bronchitis, whereas chronic azithromycin is more broadly indicated. The comparative effectiveness between these 2 treatments to reduce exacerbation rate remains unclear. OBJECTIVES: Our objective was analysis of the Veterans Health Administration (VHA) database (medication and claims data without lung function or presence of chronic bronchitis or tobacco use) to compare the effectiveness of roflumilast and azithromycin on hospitalizations and mortality. METHODS: The primary outcome of the study was cumulative incidences of first COPD-related and all-cause hospitalization. Sensitivity analysis on hospitalizations was conducted for VHA patients who also had Medicare. RESULTS: In 1302 roflumilast and 2573 azithromycin patients, the all-cause mortality rates at 1 year were 19% and 15%, respectively. The median times-to-all-cause death were 47 months (interquartile range [IQR] 16-81) for the roflumilast and 48 months (IQR 20-83) for the azithromycin groups. Roflumilast was associated with higher mortality (hazard ratio [HR] 1.16; 95% confidence interval [CI], 1.04-1.29). Roflumilast showed no significant association for COPD-related hospitalization (subdistribution HR [SHR]=1.14, 95% CI, 1.00-1.29) and all-cause hospitalization (HR 1.07, 95% CI, 0.97-1.18). For patients with Medicare (N=2030), roflumilast was associated with higher COPD-related (SHR 1.21; 95% CI, 1.05-1.41) and all-cause (SHR 1.23; 95% CI, 1.09-1.38) hospitalizations. CONCLUSIONS: Roflumilast was associated with higher hazard ratios for death, COPD-related hospitalizations, and all-cause hospitalizations in COPD patients only after adjustment for VHA and external Medicare events. Prospective clinical trials are needed to directly compare the relative efficacy of these therapies.

Medicaid Eligibility Expansions May Address Gaps In Access To Diabetes Medications.

Diabetes is a top contributor to the avoidable burden of disease. Costly diabetes medications, including insulin and drugs from newer medication classes, can be inaccessible to people who lack insurance coverage. In 2014 and 2015 twenty-nine states and the District of Columbia expanded eligibility for Medicaid among low-income adults. To examine the impacts of Medicaid expansion on access to diabetes medications, we analyzed data on over ninety-six million prescription fills using Medicaid insurance in the period January 2008-December 2015. Medicaid eligibility expansions were associated with thirty additional Medicaid diabetes prescriptions filled per 1,000 population in 2014-15, relative to states that did not expand Medicaid eligibility. Age groups with higher prevalence of diabetes exhibited larger increases. The increase in prescription fills grew significantly over time. Overall, fills for insulin and for newer medications increased by 40 percent and 39 percent, respectively. Our findings suggest that Medicaid eligibility expansions may address gaps in access to diabetes medications, with increasing effects over time.

The Impact of Delayed Hepatitis C Viral Load Suppression on Patient Risk: Historical Evidence from the Veterans Administration.

BACKGROUND: The high cost of new hepatitis C (HCV) treatments has resulted in "watchful waiting" strategies being developed to safely delay treatment, which will in turn delay viral load suppression (VLS). OBJECTIVE: To document if delayed VLS adversely impacted patient risk for adverse events and death. METHODS: 187,860 patients were selected from the Veterans Administration's (VA) clinical registry (CCR), a longitudinal compilation of electronic medical records (EMR) data for 1999-2010. Inclusion criteria required at least 6 months of CCR/EMR data prior to their HCV diagnosis and sufficient data post-diagnosis to calculate one or more FIB-4 scores. Primary outcome measures were time-to-death and time-to-a composite of liver-related clinical events. Cox proportional hazards models were estimated separately using three critical FIB-4 levels to define early and late viral response. RESULTS: Achieving an undetectable viral load before the patient's FIB-4 level exceed pre-specified critical values (1.00, 1.45 and 3.25) effectively reduced the risk of an adverse clinical events by 33-35% and death by 21-26%. However, achieving VLS after FIB-4 exceeds 3.25 significantly reduced the benefit of viral response. CONCLUSIONS: Delaying VLS until FIB-4 >3.25 reduces the benefits of VLS in reducing patient risk.

The risk of long-term morbidity and mortality in patients with chronic hepatitis C: results from an analysis of data from a Department of Veterans Affairs Clinical Registry.

IMPORTANCE: The impact of viral load suppression, genotype, race, and other factors on the risk of late-stage liver-related events in patients with hepatitis C (HCV) has been assessed previously using data from small observational cohorts or clinical trials. Data from large real-world practice samples are needed to improve risk factor estimates for late-stage liver events and death in HCV. OBJECTIVE: To describe the natural history of HCV in real-world clinical practice. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study. Patients with a detectable viral load (>25 IU/mL) and a recorded baseline genotype were selected from the Veterans Affairs (VA) HCV clinical registry (CCR), which compiles electronic medical records data from 1999 to present. EXPOSURES: Risk factors included genotype, race, age, sex, and time to achieving an observed undetected viral load. MAIN OUTCOMES AND MEASURES: The primary outcomes were time to death and time to a composite of liver-related clinical events. Secondary outcomes included the components of the composite clinical outcome. Outcomes were measured using a time-to-event format and were analyzed using Cox proportional hazards models. RESULTS A total of 28,769 of 360,857 unique HCV CCR patients met all study criteria. Only 24.3% of patients received treatment, and 16.4% of treated patients (4.0% of all patients) achieved an undetectable viral load. The unadjusted death rates were 6.8 (95% CI, 6.0-7.7) per 1000 person-years for patients who achieved viral load suppression vs 21.8 (95% CI, 21.5-22.2) deaths per 1000 person-years in patients who did not achieve this goal. Cox model results found that achieving viral suppression reduced risk of the composite clinical end point by 27% (hazard ratio [HR], 0.73 [95% CI, 0.66-0.82]) and the risk of death by 45% (HR, 0.55 [95% CI, 0.47-0.64]). Genotype 2 patients were at significantly lower risk, and genotype 3 patients were at higher risk for all study outcomes relative to genotype 1. Black patients were at lower risk for all liver events than white patients. CONCLUSION AND RELEVANCE: Achieving an undetectable viral load was associated with decreased hepatic morbidity and mortality. It remains to be determined whether newer treatment regimens can offer higher response rates with fewer adverse effects in real-world settings.

Incremental cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent clinics for non-dialysis-dependent chronic kidney disease patients.

BACKGROUND: Pharmacists successfully manage patients with anemia and chronic kidney disease (CKD), but the cost effectiveness of these programs is unknown. OBJECTIVE: To compare the cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent (ESA) clinics with that of usual care in patients with non-dialysis-dependent (NDD)-CKD. METHODS: A Markov model was used to estimate the incremental cost effectiveness of pharmacist-managed ESA clinics compared with usual care in outpatient veterans receiving ESAs for NDD-CKD in 2009. The analysis was conducted from a US Veterans Health Administration perspective with a 5-year time horizon, and the year of valuation for cost results was 2012. The effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. RESULTS: In the deterministic base case analysis, costs and effectiveness per patient over 5 years were US$13,412 and 2.096 quality-adjusted life-years (QALYs) in the pharmacist-managed ESA clinics and US$16,173 and 2.093 QALYs in usual care; ESA clinics dominated usual care. In one-way sensitivity analyses, ESA clinics no longer dominated if their patients' probability of being in the target hemoglobin range fell to 52 % (base case 71 %) or if the mean cost/patient/month of epoetin or darbepoetin in ESA clinics increased to approximately US$382 (base case US$226) or US$477 (base case US$268), respectively. When all parameters were varied simultaneously in a probabilistic sensitivity analysis, ESA clinics were favored ≥80 % of the time at willingness-to-pay thresholds of US$0-$100,000 per QALY gained. CONCLUSIONS: Pharmacist-managed ESA clinics were less costly and more effective than usual care in patients receiving ESAs for anemia and NDD-CKD. Results were robust to variation and support the use of pharmacist-managed ESA clinics.