Publications

IMPORTANCE: Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19.

OBJECTIVE: To evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19.

DESIGN: Observational cohort study.

SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States.

PARTICIPANTS: All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation.

EXPOSURES: Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants.

MAIN OUTCOMES AND MEASURES: 30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation.

RESULTS: Of 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses.

CONCLUSIONS AND RELEVANCE: Early initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.

BACKGROUND: Statutory rebates and preferred drug lists (PDLs) may result in differential use of biosimilars and generics between Medicaid fee-for-service (FFS) and managed care organizations (MCOs), particularly for branded drugs with large price increases subject to large inflation rebates, which are not retained by MCOs.

OBJECTIVE: To compare the use of 2 biosimilar/generics of branded drugs whose list price tripled in 2008-2018 across states with only FFS Medicaid, with MCOs not subject to statewide PDLs, with MCOs subject to statewide PDLs, and with MCOs where drug benefits have been carved out.

METHODS: Using 2018 Medicaid drug utilization data, we extracted reimbursement records in Q1-Q3 2018 for insulin glargine 100 IU/mL and glatiramer. We calculated the market share of the biosimilar insulin glargine and generic glatiramer among the corresponding drugs. We compared the market share of these products across 4 state groups: states with only FFS Medicaid, states with MCOs not subject to statewide PDLs for each drug, states with MCOs subject to PDLs, and states with MCOs where drug benefits have been carved out into FFS. We evaluated the correlation between state-level penetration of MCOs and share of biosimilar/generic products.

RESULTS: Nationally, the market share of these biosimilar/specialty generics was higher among MCOs than FFS (60.5% vs. 3.7% for biosimilar insulin glargine; 59.4% vs. 5.7% for generic glatiramer; all P < 0.001). The market share of these products was highest in states where MCOs were not subject to statewide PDLs for these drugs (59.1% for biosimilar insulin glargine, 52.8% for glatiramer) compared with states with MCOs subject to PDLs (2.4%, 18.0%); states with only FFS Medicaid (0.9%, 1.7%); or states where drug benefits have been carved out of MCOs (0.0%, 1.0%; all P < 0.001). There was a significant correlation between state-level MCO penetration and share of generic/biosimilar products (R = 0.50 for biosimilar insulin glargine and 0.57 for glatiramer; all P < 0.001).

CONCLUSIONS: For 2 drug classes with large price increases, use of biosimilars/generics was greater in MCOs than FFS Medicaid, specifically in states without PDL requirements for MCOs. These findings may reflect financial incentives for MCOs to use drugs with lower list prices because they do not benefit from statutory Medicaid rebates.

DISCLOSURES: No outside funding supported this study. Hernandez was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). The authors have nothing to disclose.

BACKGROUND: Atrial fibrillation (AF) is the most common heart rhythm disorder and is associated with a 5-fold increased risk of ischemic stroke. Racial/ethnic minorities and women with AF have higher rates of stroke compared to white individuals and men respectively. Oral anticoagulation reduces the risk of stroke, yet prior research has described racial/ethnic and sex-based variation in its use. We sought to examine the initiation of any oral anticoagulant (warfarin or direct-acting oral anticoagulants, DOACs) by race/ethnicity and sex in patients with incident, non-valvular AF. Further in those who initiated any anticoagulant, we examined DOAC vs. warfarin initiation by race/ethnicity and sex.

METHODS: We used claims data from a 5% sample of Medicare beneficiaries to identify patients with incident AF from 2012 to 2014, excluding those without continuous Medicare enrollment. We used logistic regression to assess the association between race/ethnicity (white, black, Hispanic), sex, and oral anticoagulant initiation (any, warfarin vs. DOAC), adjusting for sociodemographics, medical comorbidities, stroke and bleeding risk.

RESULTS: The cohort of 42,952 patients with AF included 17,935 women, 3282 blacks, and 1958 Hispanics. Overall OAC initiation was low (49.2% whites, 48.1% blacks, 47.5% Hispanics, 48.1% men, and 51.5% women). After adjusting, blacks (odds ratio (OR) 0.84; 95% CI, 0.78-0.91) were less likely than whites to initiate any oral anticoagulant with no difference observed between Hispanics and whites (OR 0.92; 95% CI, 0.83-1.01). Women were less likely than men to initiate any oral anticoagulant, OR 0.59 (95% CI 0.55-0.64). Among initiators of oral anticoagulation, DOAC use was low (35.8% whites, 29.3% blacks, 40.0% Hispanics, 41.6% men, and 42.4% women). After adjusting, blacks were less likely to initiate DOACs than whites, OR 0.75 (95% CI 0.66-0.85); the odds of DOAC initiation did not differ between Hispanic and white patients or between men and women.

CONCLUSION: In a national cohort of Medicare beneficiaries with newly-diagnosed AF, overall oral anticoagulant initiation was lower in blacks and women, with no difference observed by Hispanic ethnicity. Among oral anticoagulant initiators, blacks were less likely to initiate novel DOACs, with no differences identified by Hispanic ethnicity or sex. Identifying modifiable causes of treatment disparities is needed to improve quality of care for all patients with AF.

OBJECTIVE: To identify sociodemographic profiles of patients prescribed high-dose opioids.

DESIGN: Cross-sectional cohort study.

SETTING/PATIENTS: Veterans dually-enrolled in Veterans Health Administration and Medicare Part D, with ≥1 opioid pre-scription in 2012.

MAIN OUTCOME MEASURES: We identified five patient-level demographic characteristics and 12 community variables re-flective of region, socioeconomic deprivation, safety, and internet connectivity. Our outcome was the proportion of vet-erans receiving >120 morphine milligram equivalents (MME) for ≥90 consecutive days, a Pharmacy Quality Alliance measure of chronic high-dose opioid prescribing. We used classification and regression tree (CART) methods to identify risk of chronic high-dose opioid prescribing for sociodemographic subgroups.

RESULTS: Overall, 17,271 (3.3 percent) of 525,716 dually enrolled veterans were prescribed chronic high-dose opioids. CART analyses identified 35 subgroups using four sociodemographic and five community-level measures, with high-dose opioid prescribing ranging from 0.28 percent to 12.1 percent. The subgroup (n = 16,302) with highest frequency of the outcome included veterans who were with disability, age 18-64 years, white or other race, and lived in the Western Census region. The subgroup (n = 14,835) with the lowest frequency of the outcome included veterans who were with-out disability, did not receive Medicare Part D Low Income Subsidy, were >85 years old, and lived in communities within the second and sixth to tenth deciles of community public assistance.

CONCLUSIONS: Using CART analyses with sociodemographic and community-level variables only, we identified sub-groups of veterans with a 43-fold difference in chronic high-dose opioid prescriptions. Interactions among disability, age, race/ethnicity, and region should be considered when identifying high-risk subgroups in large populations.

BACKGROUND: Cash prices for prescription drugs vary widely in the United States.

OBJECTIVE: To describe cash price variation by retail pharmacy type for 10 generic and 6 brand-name drugs throughout the United States and stratified by ZIP code.

DESIGN: Cross-sectional study.

SETTING: Drug pricing data from GoodRx, an online tool for comparing drug prices, representing more than 60 000 U.S. pharmacies (fall 2015).

MEASUREMENTS: Cash prices for a 1-month supply of generic and brand-name drugs were ascertained. Stratified by ZIP code, relative cash prices for groups of generic and brand-name drugs were estimated for big box, grocery-based, small chain, and independent pharmacies compared with a reference group of large chain pharmacies.

RESULTS: Across 16 325 ZIP codes, 68 353 unique pharmacy stores contributed cash prices. When stratified by 5-digit ZIP code, the relative cash prices for generic drugs at big box, grocery-based, small chain, and independent pharmacies compared with those at large chain pharmacies were 0.52 (95% CI, 0.51 to 0.53), 0.82 (CI, 0.81 to 0.83), 1.51 (CI, 1.45 to 1.56), and 1.61 (CI, 1.58 to 1.64), respectively. The relative cash prices for brand-name drugs were 0.97 (CI, 0.96 to 0.97), 1.00 (CI, 0.99 to 1.00), 1.06 (CI, 1.05 to 1.08), and 1.03 (CI, 1.02 to 1.04), respectively.

LIMITATION: Results may not reflect current drug prices and do not account for point-of-sale discounts or price matching that may be offered by smaller pharmacies.

CONCLUSION: Compared with large chains, independent pharmacies and small chains had the highest cash prices for generic drugs and big box pharmacies the lowest. Relative differences in cash prices for brand-name drugs were modest across types of retail pharmacies.

PRIMARY FUNDING SOURCE: Arnold Ventures.

PURPOSE OF REVIEW: Educating clinicians on how to improve the medical management of type 2 diabetes in the modern pharmacologic era represents an enormous challenge given the number of medications available and the diversity across guideline recommendations. Academic detailing uses active social marketing techniques to deliver in-office, face-to-face educational encounters between a trained clinical educator (academic detailer) and a primary care clinician and can improve the quality of prescribing and management decisions, leading to better patient outcomes.

RECENT FINDINGS: This updated review provides context on how academic detailing programs can improve diabetes-related clinical knowledge and practice among primary care providers, incorporating the perspective of a field-based academic detailer. It also profiles 4 diabetes-specific academic detailing programs varying in geographic scope and detailing approach, based in Massachusetts, Pennsylvania, Vermont, and Saskatchewan Province (Canada). Academic detailing can effectively overcome challenges to increasing the evidence-based use of newer glucose-lowering medications in primary care settings.

BACKGROUND: Hospitalizations contribute significantly to the annual health care expenditure for inflammatory bowel disease (IBD), and reducing cost of care without compromising outcomes is a rising priority. Teaching hospitals (THs) have higher costs and utilize trainees in care to a greater extent than community hospitals, and it is unknown how hospital teaching status (HTS) affects outcomes. We therefore sought to investigate the impact of HTS on IBD hospitalization outcomes.

METHODS: We used the Vizient clinical database to identify patients hospitalized between October 1, 2014, and March 31, 2018, for IBD. Vizient hospitals were divided into major THs, minor THs, and non-THs. We used multivariable linear regression of aggregated discharge data to assess the association of HTS with mean length of stay (LOS), mean direct cost (DC), 30-day readmission rate (RR), and in-hospital mortality rate (MR), while adjusting for demographics and disease complexity.

RESULTS: Vizient included 29,863 discharges among 291 hospitals for ulcerative colitis (UC) and 62,698 discharges among 314 hospitals for Crohn's disease (CD) between October 1, 2014, and March 31, 2018. Unadjusted mean LOS, mean DC, and 30-day RR were greater among THs for both UC and CD. Unadjusted MR was greater among major THs for UC but not CD. After multivariable analysis, only 30-day RR for UC was increased in major THs relative to non-THs (1.98%; 95% confidence interval, 0.33%-3.61%).

CONCLUSIONS: Differences in metrics of cost-effective hospital care for patients with IBD appear to be driven by disease severity rather than HTS. Future research should attempt to better characterize factors driving resource utilization for IBD hospitalizations.

It is unknown to what extent rising drug costs are due to inflation in the prices of existing drugs versus the entry of new products. We used pricing data from First Databank and pharmacy claims from UPMC Health Plan to quantify the contribution of new versus existing drugs to the changes in costs of oral and injectable drugs used in the outpatient setting in 2008-16. The costs of oral and injectable brand-name drugs increased annually by 9.2 percent and 15.1 percent, respectively, largely driven by existing drugs. For oral and injectable specialty drugs, costs increased 20.6 percent and 12.5 percent, respectively, with 71.1 percent and 52.4 percent of these increases attributable to new drugs. Costs of oral and injectable generics increased by 4.4 percent and 7.3 percent, respectively, driven by new drug entry. The rising costs of generic and specialty drugs were mostly driven by new product entry, whereas the rising costs of brand-name drugs were due to existing drug price inflation.