Publications

BACKGROUND: Most states have recently passed laws requiring prescribers to use prescription drug monitoring programs (PDMPs) before prescribing opioid medications. The impact of these mandates on discontinuing chronic opioid therapy among Veterans managed in the Veterans Health Administration (VA) is unknown. We assess the association between the earliest of these laws and discontinuation of chronic opioid therapy in Veterans receiving VA health care.

METHODS: We conducted a comparative interrupted time-series study in the 5 states mandating PDMP use before August 2013 (Ohio, West Virginia, Kentucky, New Mexico, and Tennessee), adjusting for trends in the 17 neighboring control states without such mandates. We modeled 25 months of prescribing for each state centered on the month the mandate became effective. We included Veterans prescribed long-term outpatient opioid therapy (305 of the preceding 365 d). Our outcomes were discontinuation of chronic opioid therapy (primary outcome) and the average daily quantity of opioids per Veteran over the following 6 months (secondary outcome).

RESULTS: We included 250 monthly cohorts with 225,665 unique Veterans and 3.4 million Veteran-months. Baseline discontinuation rates before the PDMP mandates were 0.4%-2.7% per month. Kentucky saw a discontinuation increase of 1 absolute percentage point following its PDMP mandate which decreased over time. The other 4 states had no significant association between their mandates and change in opioid discontinuation. There was no evidence of decreasing opioid quantities following PDMP mandates.

CONCLUSION: We did not find consistent evidence that state laws mandating provider PDMP use were associated with the discontinuation of chronic opioid therapy within the VA for the time period studied.

UNLABELLED: Regional variation in procedure use often reflects the uncertainty about the risks and benefit of procedures. In Switzerland, regional variation in vertebroplasty and balloon kyphoplasty rates was high, although the variation declined between 2013 and 2018. Substantial parts of the variation remained unexplained, and likely signal unequal access and differing physician opinion.

PURPOSE: To assess trends and regional variation in percutaneous vertebroplasty (VP) and balloon kyphoplasty (BKP) use across Switzerland.

METHODS: We conducted a population-based analysis using patient discharge data from all Swiss acute care hospitals for 2013-2018. We calculated age/sex-standardized mean procedure rates and measures of variation across VP/BKP-specific hospital areas (HSAs). We assessed the influence of potential determinants of variation using multilevel regression models with incremental adjustment for demographics, cultural/socioeconomic, health, and supply factors.

RESULTS: We analyzed 7855 discharges with VP/BKP from 31 HSAs. The mean age/sex-standardized procedure rate increased from 16 to 20/100,000 persons from 2013 to 2018. While the variation in procedure rates across HSAs declined, the overall variation remained high (systematic component of variation from 56.8 to 6.9 from 2013 to 2018). Determinants explained 52% of the variation.

CONCLUSIONS: VP/BKP procedure rates increased and regional variation across Switzerland declined but remained at a high level. A substantial part of the regional variation remained unexplained by potential determinants of variation.

INTRODUCTION: Gastrointestinal (GI) symptoms and disorders affect an increasingly large group of veterans. Opioid use may be rising in this population, but this is concerning from a patient safety perspective, given the risk of dependence and lack of evidence supporting opioid use to manage chronic pain. We examined the characteristics of opioid prescriptions and factors associated with chronic opioid use among chronic GI patients dually enrolled in the DVA and Medicare Part D.

MATERIALS AND METHODS: In this retrospective cohort study, we used linked, national patient-level data (from April 1, 2011, to December 31, 2014) from the VA and Centers for Medicare & Medicaid Services to identify chronic GI patients and observe opioid use. Veterans who had a chronic GI symptom or disorder were dually enrolled in VA and Part D and received ≥1 opioid prescription dispensed through the VA, Part D, or both. Chronic GI symptoms and disorders included chronic abdominal pain, chronic pancreatitis, inflammatory bowel diseases, and functional GI disorders. Key outcome measures were outpatient opioid prescription dispensing overall and chronic opioid use, defined as ≥90 consecutive days of opioid receipt over 12 months. We described patient characteristics and opioid use measures using descriptive statistics. Using multiple logistic regression modeling, we generated adjusted odds ratios and 95% CIs to determine variables independently associated with chronic opioid use. The final model included variables outlined in the literature and our conceptual framework.

RESULTS: We identified 141,805 veterans who had a chronic GI symptom or disorder, were dually enrolled in VA and Part D, and received ≥1 opioid prescription dispensed from the VA, Part D, or both. Twenty-six percent received opioids from the VA only, 69% received opioids from Medicare Part D only, and 5% were "dual users," receiving opioids through both VA and Part D. Compared to veterans who received opioids from the VA or Part D only, dual users had a greater likelihood of potentially unsafe opioid use outcomes, including greater number of days on opioids, higher daily doses, and higher odds of chronic use.

CONCLUSIONS: Chronic GI patients in the VA may be frequent users of opioids and may have a unique set of risk factors for unsafe opioid use. Careful monitoring of opioid use among chronic GI patients may help to begin risk stratifying this group. and develop tailored approaches to minimize chronic use. The findings underscore potential nuances within the opioid epidemic and suggest that components of the VA's Opioid Safety Initiative may need to be adapted around veterans at a higher risk of opioid-related adverse events.

IMPORTANCE: Atrial fibrillation is a common cardiac rhythm disturbance causing substantial morbidity and mortality that disproportionately affects racial/ethnic minority groups. Anticoagulation reduces stroke risk in atrial fibrillation, yet studies show it is underprescribed in racial/ethnic minority patients.

OBJECTIVE: To compare initiation of anticoagulant therapy by race/ethnicity for patients in the Veterans Health Administration (VA) system with atrial fibrillation.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 111 666 patients within the VA system with incident atrial fibrillation between January 1, 2014, and December 31, 2018. Data were analyzed between December 1, 2019, and March 31, 2020.

EXPOSURES: Any anticoagulation was defined as receipt of warfarin or direct-acting oral anticoagulants, apixaban, dabigatran, edoxaban, or rivaroxaban.

MAIN OUTCOMES AND MEASURES: Initiation of any anticoagulation (or direct-acting oral anticoagulant therapy in those who initiated any anticoagulation) was examined within 90 days of an index atrial fibrillation diagnosis.

RESULTS: Our final cohort comprised 111 666 patients (109 386 men [98.0%] and 95 493 White patients [85.5%]; mean [SD] age, 72.9 [10.4] years). A total of 69 590 patients (62.3%) initiated any anticoagulant therapy, varying 10.5 percentage points by race/ethnicity (P < .001); initiation was lowest in Asian (52.2% [n = 676]) and Black (60.3% [n = 6177]) patients and highest in White patients (62.7% [n = 59 881]). Among anticoagulant initiators, 45 381 (65.2%) used direct-acting oral anticoagulants, varying 7.2 percentage points by race/ethnicity (P < .001); initiation was lowest in Hispanic (58.3% [n = 1470]), American Indian/Alaska Native (59.8% [n = 201]), and Black (60.9% [n = 3763]) patients and highest in White patients (66.0% [n = 39 502). Compared with White patients, the odds of initiating any anticoagulant therapy were significantly lower for Asian (adjusted odds ratio [aOR], 0.82; 95% CI, 0.72-0.94) and Black (aOR, 0.90; 95% CI 0.85-0.95) patients. Among initiators, the adjusted odds of direct-acting oral anticoagulant initiation were significantly lower for Hispanic (aOR, 0.79; 95% CI, 0.70-0.89), American Indian/Alaska Native (aOR, 0.75; 95% CI, 0.57-0.99), and Black (aOR, 0.74; 95% CI 0.69-0.80) patients.

CONCLUSIONS AND RELEVANCE: This cohort study found that in patients with incident atrial fibrillation managed in the VA system, race/ethnicity was independently associated with initiating any anticoagulant therapy and direct-acting oral anticoagulant use among anticoagulant initiators. Understanding the reasons for these treatment disparities is essential to improving equitable atrial fibrillation management and outcomes among racial/ethnic minority patients treated in the VA system.

Health system data incompletely capture the social risk factors for drug overdose. This study aimed to improve the accuracy of a machine-learning algorithm to predict opioid overdose risk by integrating human services and criminal justice data with health claims data to capture the social determinants of overdose risk. This prognostic study included Medicaid beneficiaries (n = 237,259) in Allegheny County, Pennsylvania enrolled between 2015 and 2018, randomly divided into training, testing, and validation samples. We measured 290 potential predictors (239 derived from Medicaid claims data) in 30-day periods, beginning with the first observed Medicaid enrollment date during the study period. Using a gradient boosting machine, we predicted a composite outcome (i.e., fatal or nonfatal opioid overdose constructed using medical examiner and claims data) in the subsequent month. We compared prediction performance between a Medicaid claims only model to one integrating human services and criminal justice data with Medicaid claims (i.e., integrated model) using several metrics (e.g., C-statistic, number needed to evaluate [NNE] to identify one overdose). Beneficiaries were stratified into risk-score decile subgroups. The samples (training = 79,087, testing = 79,086, validation = 79,086) had similar characteristics (age = 38±18 years, female = 56%, white = 48%, having at least one overdose = 1.7% during study period). Using the validation sample, the integrated model slightly improved on the Medicaid claims only model (C-statistic = 0.885; 95%CI = 0.877-0.892 vs. C-statistic = 0.871; 95%CI = 0.863-0.878), with small corresponding improvements in the NNE and positive predictive value. Nine of the top 30 most important predictors in the integrated model were human services and criminal justice variables. Using the integrated model, approximately 70% of individuals with overdoses were members of the top risk decile (overdose rates in the subsequent month = 47/10,000 beneficiaries). Few individuals in the bottom 9 deciles had overdose episodes (0-12/10,000). Machine-learning algorithms integrating claims and social service and criminal justice data modestly improved opioid overdose prediction among Medicaid beneficiaries for a large U.S. county heavily affected by the opioid crisis.

OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States.

DESIGN: Observational cohort study.

SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system.

PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation.

MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion.

RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses.

CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission.

BACKGROUND: In a cohort of Veterans dually enrolled in the Department of Veterans Affairs (VA) and Medicare Part D, we sought to describe high-dose daily opioid use among Veterans with unexplained gastrointestinal (GI) symptoms and structural GI diagnoses and examine factors associated with high-dose use.

METHODS: We used linked national patient-level data from the VA and Centers for Medicare and Medicaid Services (CMS). We grouped patients into 3 subsets: those with unexplained GI symptoms (e.g., chronic abdominal pain); structural GI diagnoses (e.g., chronic pancreatitis); and those with a concurrent unexplained GI symptom and structural GI diagnosis. High-dose daily opioid use levels were examined as a binary variable [≥ 100 morphine milligram equivalents (MME)/day] and as an ordinal variable (50-99 MME/day, 100-119 MME/day, or ≥ 120 MME/day).

RESULTS: We identified 141,805 chronic GI patients dually enrolled in VA and Part D. High-dose opioid use was present in 11% of Veterans with unexplained GI symptoms, 10% of Veterans with structural GI diagnoses, and 15% of Veterans in the concurrent GI group. Compared to Veterans with only an unexplained GI symptom or structural diagnosis, concurrent GI patients were more likely to have higher daily opioid doses, more opioid days ≥ 100 MME, and higher risk of chronic use. Factors associated with high-dose use included opioid receipt from both VA and Part D, younger age, and benzodiazepine use.

CONCLUSIONS: A significant subset of chronic GI patients in the VA are high-dose opioid users. Efforts are needed to reduce high-dose use among Veterans with concurrent GI symptoms and diagnoses.

This cohort study used Medicaid data to examine trends in the use of and spending for hemophilia pharmaceuticals from 2005 to 2020.

BACKGROUND: List prices of tumor necrosis factor (TNF) inhibitors drastically increased during the last decade, but previous research has shown that half of these increases were offset by rising manufacturer discounts. It remains unclear to what extent manufacturers' discounts have offset increases in list prices of each self-administered injectable TNF inhibitor. Evaluating trends in net prices and discounts at the product level will be paramount in understanding the role of competition in the biologic market. OBJECTIVES: To (a) describe product-level changes in net prices of each self-administered injectable TNF inhibitor available in 2007-2019 and (b) quantify to what extent manufacturer discounts have offset increases in list prices. METHODS: We obtained 2007-2019 pricing data for etanercept, adalimumab, certolizumab, and golimumab from the investment firm SSR Health, which uses company-reported sales to estimate net prices and discounts for brand products manufactured by publicly traded companies. For each drug and year, we calculated annual costs of treatment for patients with rheumatoid arthritis based on list and net prices and discounts in Medicaid and other payers. RESULTS: From 2007-2019, list prices of etanercept and adalimumab increased by 293% and 295%, respectively; however, discounts offset 47% and 45% of these increases, leading to net price increases of 171% and 203%. List prices of golimumab and certolizumab increased by 183% and 182%, respectively, but with discounts offsetting 58% and 59% of these increases, net prices increased by 103% and 109%. Net prices of golimumab started to decrease after 2016, while net prices of adalimumab and certolizumab experienced their first drop in 2019. Across the study period, discounts in Medicaid and in other payers increased, respectively, from 21% to 85% and 6% to 32% for etanercept; from 26% to 88% and 19% to 35% for adalimumab; from 28% to 63% and 22% to 46% for golimumab; and from 29% to 83% and 27% to 47% for certolizumab. CONCLUSIONS: Despite growing manufacturer discounts, net prices of self-administered injectable TNF inhibitors still increased at a mean annual rate of 9.6% in 2007-2019. This led to net prices tripling for adalimumab and more than doubling for etanercept, golimumab, and certolizumab. DISCLOSURES: This study was funded by the Myers Family Foundation. Hernandez is funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Hernandez has served on Pfizer's scientific advisory board. The other authors have nothing to disclose.

BACKGROUND: Oral anticoagulation (OAC) is recommended for the prevention of stroke in atrial fibrillation (AF). However, only 50%-60% of AF patients in the United States are treated with OAC, and 60% of them adhere to OAC therapy over time. OBJECTIVES: To (1) compare adherent use of OAC between AF patients who received primary care from practices involved in shared-savings models and patients who received care from practices not involved in shared savings and (2) examine the trend of adherence to OAC over time. Because OAC can save downstream medical costs associated with averted stroke events, we hypothesized that OAC adherence would be higher among patients receiving care from practices involved in shared savings. METHODS: Using 2014-2019 claims data from a health insurer in western Pennsylvania, we identified 20,637 AF patients from 2015-2018. Patients were followed from the first AF diagnosis (index date) for 12 months or until disenrollment. We categorized patients according to the payment model of the practice from which they received primary care: shared savings (n = 8,844) and no shared savings (n = 11,793). The primary outcome was adherent use of OAC therapy, which was defined as having at least 80% of the followup period covered with OAC. Secondary outcomes included adherent use of direct oral anticoagulants (DOACs) and adherent use of warfarin. We constructed logistic regression models to assess the association between involvement in shared savings and adherent use of OAC, while controlling for demographics, clinical characteristics, and index year. RESULTS: 34% of patients in the shared-savings group adhered to OAC, compared with 32.7% in the no shared-savings group (P = 0.04). After adjustment, adherence was higher for the shared-savings group for OAC (adjusted odds ratio [aOR] = 1.07, 95% CI = 1.01-1.14) and warfarin (aOR = 1.11, 95% CI = 1.02-1.20) compared with the no shared-savings group. However, the odds of adherent use of DOACs did not statistically differ between shared savings and no shared savings (aOR = 0.99, 95% CI = 0.91-1.08). The odds of adherent OAC use increased over time: the aOR of adherent use of OAC was 1.21 (95% CI = 1.09-1.34) for index year 2016; 1.50 (95% CI = 1.36-1.67) for 2017; and 1.78 (95% CI 1.60-1.98) for 2018, all compared with 2015. CONCLUSIONS: Receipt of primary care from a practice involved in shared savings was associated with a higher adherent use of OAC and warfarin for patients with atrial fibrillation. Furthermore, adherent use of OAC improved over time for both treatment groups. Our research demonstrates that the alignment of financial incentives between providers and insurers may improve the use of therapies with downstream cost-saving potential. DISCLOSURES: This project was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Hernandez has received consulting fees from Pfizer and BMS, outside of the submitted work. The other authors have nothing to disclose.