Medication Safety Events After Acute Myocardial Infarction Among Veterans Treated at VA Versus Non-VA Hospitals.

INTRODUCTION: Fragmentation of health care across systems can contribute to mistakes in prescribing and filling medications among patients treated for myocardial infarction (MI). We sought to compare omissions, duplications, and delays in outpatient medications used for secondary prevention among veterans treated for MI at Veterans Affairs (VA) versus non-VA hospitals. METHODS: We utilized national VA and Centers for Medicare and Medicaid Services data (2012-2018) to identify veterans 65 years or older hospitalized for MI and measured the use of outpatient medications for secondary prevention in the 30 days after MI among those treated at VA versus non-VA hospitals. RESULTS: A total of 118,456 veterans experiencing MI were included; of which 102,209 were hospitalized at non-VA hospitals. An omission in any medication class occurred more frequently among veterans treated at non-VA versus VA hospitals (82.8% vs 67.8%, P < 0.001). In multivariable modeling, the odds of omissions in any medication class were higher among those treated at non-VA versus VA hospitals (odds ratio: 3.04; 95% CI: 2.88-3.20). Duplications occurred more frequently in veterans treated at non-VA versus VA hospitals: 1.9% versus 1.6% had 1 or more for non-VA versus VA hospitals ( P < 0.001). Veterans treated at non-VA hospitals were more likely to have delays of 3 days or more in prescription fills after hospital discharge (88.4% vs 70.6% across all classes, P < 0.001). CONCLUSIONS: Omissions, duplications, and delays in outpatient prescribing of secondary prevention medications were more common among 118,456 veterans treated at non-VA versus VA hospitals for MI. Interventions aimed at improving care transitions and optimizing medication use among veterans treated at non-VA hospitals should be implemented.

Geographic distribution of United States clinical trial sites utilized for guideline changing studies of cholesterol management.

BACKGROUND: This study aimed to evaluate the geographic distribution of United States (US) clinical trial sites utilizedfor guideline changing studies of cholesterol management. METHODS: Randomized trials evaluating pharmacologic interventions for cholesterol treatment and reporting location data (ie, zip code of trial sites) were identified. Location data was abstracted from ClinicalTrials.gov. RESULTS: Half of US counties were over 30 miles from a study site and, social determinants of health were more favorable in counties with versus without clinical trial sites. CONCLUSIONS: Stakeholders such as regulatory bodies andtrial sponsors should incentivize and support infrastructure that would enable a larger number of US counties to be utilized for clinical trial sites. TRIAL REGISTRATION: Not applicable.

Impact of Race and Ethnicity on Severe Hypoglycemia Associated with Sulfonylurea Use for Type 2 Diabetes among Veterans.

Sulfonylureas are associated with hypoglycemia. Whether a racial/ethnic disparity in this safety outcome exists is unknown. We sought to assess the impact of race/ethnicity on severe hypoglycemia associated with sulfonylurea use for type 2 diabetes (T2D). Using Veterans Affairs and Medicare data, Veterans initially receiving metformin monotherapy for T2D between 2004 and 2006 were identified. Sulfonylurea use (either alone or via the addition of a prescription for a sulfonylurea to metformin) was captured and compared to remaining on metformin alone during the follow-up period (2007-2016). Hazard ratios (HR) and 95% confidence intervals (CI) from longitudinal competing risk Cox models were used to measure the association between sulfonylurea use and severe hypoglycemia defined as hospitalization for hypoglycemia. A total of 113,668 Veterans with T2D were included. A higher risk of severe hypoglycemia was associated with the receipt of sulfonylurea prescriptions versus remaining on metformin alone across all groups. The effect was largest among Hispanic Veterans (HR: 7.59, 95%CI:4.32-13.33), followed by Veterans in the other race/ethnicity cohort (HR: 4.57, 95%CI:2.50-8.36) and Non-Hispanic Black Veterans (HR: 3.67, 95%CI:2.78-4.85). The effect was smallest among Non-Hispanic White Veterans (HR: 3.11, 95%CI:2.77-3.48). In conclusion, a higher risk of severe hypoglycemia associated with sulfonylurea prescriptions was observed across all analyses. The relationship was most pronounced for Hispanic Veterans, who had nearly 8 times the risk of severe hypoglycemia with sulfonylureas versus remaining on metformin alone.

Sulfonylureas as second line therapy for type 2 diabetes among veterans: Results from a National Longitudinal Cohort Study.

AIMS: To assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone. MATERIALS AND METHODS: This was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes. RESULTS: Switching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7-19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively). CONCLUSIONS: Switching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy.

First hepatitis B vaccine uptake in neonates prior to and during the COVID-19 pandemic.

INTRODUCTION: Routine vaccination for hepatitis B is recommended at birth, and most infants should be vaccinated within 24 h of life. Historically, vaccination rates have been less than ideal, and routine vaccination has been further complicated by the COVID-19 pandemic, with decreased uptake of many vaccines. This retrospective study assessed hepatitis B vaccination rates at birth before and after the start of the COVID-19 pandemic and explored the factors associated with lower vaccination rates. METHODS: Infants born at a single academic medical center in Charleston, South Carolina from November 1, 2018 through June 30, 2021 were identified. Infants were excluded if they died or received ≥ 7 days of systemic steroid therapy within the first 37 days of life. Maternal and infant baseline characteristics and uptake of the first hepatitis B vaccine during hospital admission were recorded. RESULTS: A total of 7808 infants were included in the final analysis, with an overall vaccine uptake of 91.6 %. Of the 3880 neonates in the pre-pandemic group, 3583 (92.3 %) were vaccinated, versus 3571 (90.9 %) of 3928 neonates in the pandemic group (rate difference = 1.4 %; 95 % confidence interval -2.8 % to 5.7 %, p = 0.52). Factors independently associated with lower vaccine uptake included being of non-Hispanic white race, born to a married mother, birth weight < 2 kg, and parental refusal of erythromycin eye ointment at birth. CONCLUSION: The COVID-19 pandemic did not significantly affect the uptake of inpatient neonatal hepatitis B vaccination. Several patient-specific factors were associated with suboptimal vaccination rates in this population.

Risk Factors for Antibiotic Resistant Urinary Pathogens in Patients Discharged From the Emergency Department.

Purpose: Urinary tract infections (UTIs) are one of the most common indications for antimicrobial use in the emergency department (ED). Appropriate empiric selection is crucial to ensure optimal care while limiting broad-spectrum antibiotic use. The primary objective of this study was to evaluate the relationship between patient-specific risk factors and drug resistant urinary pathogens in patients discharged from the ED and followed by Emergency Medicine Pharmacists (EMPs). Methods: This was a single-center, retrospective chart review of adult (≥18 years old) patients with positive urine cultures discharged from the ED. The association between risk factors and pathogen resistance to ≥1 classes of antibiotics was evaluated using multivariate logistic regression. Risk factors included the following: hospitalization within the previous 30 days, intravenous antibiotic use within 90 days, diabetes, clinical atherosclerotic cardiovascular disease, psychiatric disorder, dementia, current antibiotic use for any indication, previous lifetime history of UTIs, indwelling or intermittent catheterization, hemodialysis, previous lifetime history of a urologic procedure, urinary tract abnormality, immunosuppressive disease or medications, current residence in a nursing or rehabilitation facility, and history of a multidrug resistant organism (MDRO). Results: A total of 1018 patients were included. There was an increase in the odds of antibiotic resistance in patients with cystitis and ≥2 risk factors (Odds Ratio [OR] = 1.70, 95% CI = 1.24-2.32). In those with pyelonephritis, there was a non-significant increase in the odds of resistance for those with ≥2 risk factors (OR = 1.83, 95% CI = 0.98-3.42). Patients with pyelonephritis discharged on inappropriate antibiotics were more likely to return to the ED within 30 days (P = .03). Conclusions: For patients with cystitis discharged from the ED, those with ≥2 patient-specific risk factors had significantly increased odds of antibiotic resistance. Patients with pyelonephritis, but not cystitis, who were discharged on inappropriate antibiotics were more likely to return to the ED within 30 days. In conjunction with an EMP culture follow-up program, the identification of risk factors for antimicrobial resistance can be used to design more patient-specific empiric antibiotic selections.

Effectiveness and Safety of Twice- Versus Thrice-Daily Subcutaneous Heparin for Venous Thromboembolism Prophylaxis at a Large Academic Medical Center.

BACKGROUND: Dosing variation of subcutaneous unfractionated heparin (UFH) exist for venous thromboembolism prophylaxis (VTEP). OBJECTIVE: The purpose of this study was to compare the safety and effectiveness of thrice-daily (TID) versus twice-daily (BID) administration of UFH during a heparin shortage for VTEP. METHODS: A single-center retrospective analysis was conducted in patients with orders for BID subcutaneous UFH during a heparin shortage from September 1, 2019, to February 4, 2020. These patients were matched to patients with TID subcutaneous UFH orders from January 1, 2019, to May 31, 2019. The primary outcome was the incidence of deep-vein thrombosis or pulmonary embolism confirmed by imaging during hospitalization. The secondary outcome was the incidence of major or clinically relevant nonmajor bleeding events as defined by International Society on Thrombosis and Haemostasis (ISTH) definitions. RESULTS: A total of 277 patients with orders for BID UFH and meeting inclusion criteria were evaluated and matched to patients who received TID UFH. After the exclusion criteria were implemented, 510 patients remained in the TID group. The primary outcome occurred in 4% of patients in the BID group and 3% in the TID group (P = 0.645). Major bleeding or clinically relevant nonmajor bleeding events occurred in 10% of patients in the BID group and 8% in the TID group (P = 0.310). CONCLUSION AND RELEVANCE: There was no difference in effectiveness or safety of TID versus BID subcutaneous UFH for VTEP. During a heparin shortage, transitioning patients to BID UFH for VTEP to conserve supply may be considered.

Development of a Pharmacy Residency Research Certificate Program.

Background: Similar to teaching certificate programs, which have been incorporated in many pharmacy residencies to improve teaching skills, resident research certificate programs could provide residents with more exposure to biostatistics and research design. However, few research certificate programs have been described. Objective: To assess the impact of a research certificate program on residents' attitude toward, confidence in, and knowledge of research. Methods: A resident research certificate program was created for the 2018-2019 residency class at our institution, which included 33 pharmacy residents (15 postgraduate year-1 [PGY1] and 18 PGY2 residents). The program consisted of 7 sessions aimed at providing residents with research training. To earn a certificate, participants were required to attend 6 or more sessions and achieve a score greater than or equal to 70% on a postassessment. An optional questionnaire assessing attitude, confidence, and knowledge was also administered at baseline and following the certificate program. Results: Of the 33 residents participating in the research certificate program, 21 (9 PGY1 and 12 PGY2) residents completed both the baseline and follow-up questionnaire and were included in the analysis. All items assessing attitude and 3 of 6 items assessing confidence improved significantly following the certificate program when compared to baseline (P < .05 for all). Median knowledge scores were no different on the baseline versus follow-up questionnaire (P = .54). Conclusions: After completing a research certificate program, resident knowledge scores did not differ from baseline, but attitudes toward research and confidence appeared to improve. Research certificate programs could be an avenue for providing pharmacy residents with increased exposure to and comfort with biostatistics and research design.

Medication adherence to injectable glucagon-like peptide-1 (GLP-1) receptor agonists dosed once weekly vs once daily in patients with type 2 diabetes: A meta-analysis.

BACKGROUND: Suboptimal medication adherence has been associated with increased resource utilisation and mortality among patients with type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly important in the treatment of T2D. However, medications in this class differ considerably in their dosing frequency, which may impact adherence. We sought to perform a meta-analysis to compare adherence to injectable GLP-1RAs dosed once weekly vs once daily in patients with T2D. METHODS: Medline and Scopus were searched from 1/2005 to 7/2020 using keywords and MeSH terms pertaining to adherence and GLP-1RAs. Studies of adults with T2D were included if they compared adherence (as measured by proportion of days covered [PDC]) to injectable GLP-1RAs dosed once weekly vs once daily. A meta-analysis of non-overlapping studies was performed to evaluate the primary outcome of non-adherence, defined as the proportion of patients with a PDC < 80. RESULTS: A total of 7 studies evaluating 75 159 patients (range: 2886-30 097) with T2D were included. The follow-up periods of included studies ranged from 6 to 12 months. Injectable GLP-1RAs dosed once weekly were either dulaglutide, albiglutide or exenatide extended release; while liraglutide was the injectable once daily agent evaluated in all included studies. Upon meta-analysis, once weekly GLP-1RA dosing was associated with an 11% lower risk of non-adherence compared to once daily dosing (risk ratio = 0.89; 95% confidence interval = 0.83-0.95; I2  = 89%). CONCLUSION: Once weekly dosing of injectable GLP-1RAs was associated with better adherence vs once daily dosing among patients with T2D. These findings coupled with the known detrimental consequences of non-adherence suggest that dosing frequency is an important factor to consider when selecting a GLP-1RA.

Intravenous insulin for the management of non-emergent hyperglycemia in the emergency department.

PURPOSE: There is currently no consensus regarding the necessity of emergency department (ED) glucose reduction to manage hyperglycemia in patients presenting without a hyperglycemic emergency. Known consequences of intravenous (IV) insulin administration include hypoglycemia, hypokalemia, and increased ED length of stay. The primary objective of this study was to assess the impact of IV regular insulin on glucose reduction and ED length of stay in patients presenting to the ED with non-emergent hyperglycemia. Secondary objectives included the characterization of potential adverse events. METHODS: This was a retrospective, observational study of patients ≥18 years who received IV regular insulin and were discharged from the ED at a large academic Trauma Center. Univariate and multivariable regression analyses were utilized to determine if an association existed between IV insulin administration and blood glucose as well as ED length of stay. RESULTS: A total of 405 patients were included in the analysis. An insulin dose >5 units was associated with a greater reduction in blood glucose (difference = 37.4 mg/dL; p < .001) but no difference in ED length of stay relative to ≤5 units. Furthermore, 7.9% of patients developed hypokalemia and 0.4% developed hypoglycemia. CONCLUSION: The use of >5 units of IV regular insulin for the management of isolated hyperglycemia in the ED was associated with a modest reduction in blood glucose and no difference in ED length of stay compared with those that received ≤5 units. However, use of IV insulin for this purpose resulted in a 7.9% occurrence of hypokalemia.

Joint effect of race/ethnicity or location of residence and sex on low density lipoprotein-cholesterol among veterans with type 2 diabetes: a 10-year retrospective cohort study.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of death among United States women. Rural residence and ethnic-minority status are individually associated with increased CV mortality. Managing dyslipidemia is important in the prevention of CV mortality. However, the impact of race/ethnicity and location of residence on sex differences in dyslipidemia management is not well understood. Therefore, we sought to understand the joint effects of race/ethnicity and location of residence on lipid management differences between veteran men and women with type 2 diabetes (T2D). METHODS: Veterans Health Administration and Centers for Medicare and Medicaid Services data were used to perform a longitudinal cohort study of veterans with T2D (2007-2016). Mixed effects logistic regression with a random intercept was used to model the association between sex and low-density lipoprotein (LDL) > 100 mg/dL and its interaction with race/ethnicity and location of residence after adjusting for all measured covariates. RESULTS: When female sex and rural location of residence were both present, they were associated with an antagonistic harmful effect on LDL. Similar antagonistic harmful effects on LDL were observed when the joint effect of female sex and several minority race/ethnicity groups were evaluated. After adjusting for measured covariates, the odds of LDL > 100 mg/dL were higher for urban women (OR = 2.66, 95%CI 2.48-2.85) and rural women (OR = 3.26, 95%CI 2.94-3.62), compared to urban men. The odds of LDL > 100 mg/dL was the highest among non-Hispanic Black (NHB) women (OR = 5.38, 95%CI 4.45-6.51) followed by non-Hispanic White (NHW) women (OR = 2.59, 95%CI 2.44-2.77), and Hispanic women (OR = 2.56, 95%CI 1.79-3.66). CONCLUSION: Antagonistic harmful effects on LDL were observed when both female sex and rural location of residence were present. These antagonistic effects on LDL were also present when evaluating the joint effect of female sex and several minority race/ethnicity groups. Disparities were most pronounced in NHB and rural women, who had 5.4 and 3.3 times the odds of elevated LDL versus NHW and urban men after adjusting for important covariates. These striking effect sizes in a population at high cardiovascular risk (i.e., older with T2D) suggest interventions aimed at improving lipid management are needed for individuals falling into one or more groups known to face health disparities.

An Evaluation of Statin Use Among Patients with Type 2 Diabetes at High Risk of Cardiovascular Events Across Multiple Health Care Systems.

BACKGROUND: Patients with more than one chronic condition often receive care from several providers and facilities, which may lead to fragmentation of care. Poor care coordination in dual health care system use has been associated with increased emergency department visits, hospitalizations, and costs. OBJECTIVE: Dual health care system use is increasing among veterans, and we sought to evaluate the effect of dual health care system use on statin treatment in veterans with type 2 diabetes at high risk of cardiovascular events, using varying degrees of Centers for Medicare & Medicaid Services (CMS) services. METHODS: This was a 10-year retrospective longitudinal cohort study of national clinical and administrative data that included 689,138 veterans with type 2 diabetes who were aged 65 years or older on January 1, 2006. Patients were followed from January 1, 2007, until December 31, 2016. Administrative and clinical data from the Veterans Health Administration's (VHA) Corporate Data Warehouse were merged with CMS inpatient, outpatient, and pharmacy data. Statin use was defined as any therapy and subcategorized as high versus low or moderate intensity per the American College of Cardiology/American Heart Association guidelines. Marginal generalized estimating equation-type models for longitudinal data were used to model the association between dual health care utilization status (< 50%, 50%-80%, and > 80% VHA utilization, with the first group serving as the reference group) and statin use after adjusting for measured covariates. RESULTS: The mean ages at baseline for each group were similar and ranged between 75.4 and 76.9 years. For the outcome of any statin use, the group with < 50% VHA utilization was significantly less likely to receive statin therapy compared with the group with > 80% VHA utilization (OR = 0.26, 95% CI = 0.26-0.26), while the group with 50%-80% VHA utilization was slightly more likely (OR = 1.05, 95% CI = 1.04-1.07). Similarly, for the high-intensity versus low-/moderate-intensity or no statins outcome, the group with < 50% VHA utilization was significantly less likely to receive a high-intensity statin compared with the group with > 80% VHA utilization (OR = 0.56, 95% CI = 0.55-0.57), while the group with 50%-80% VHA utilization was only slightly less likely (OR = 0.95, 95% CI =0.94-0.96). CONCLUSIONS: Among veterans with diabetes at high risk of cardiovascular events, dual health care system utilization status appeared to affect statin use. We observed lower odds for any statin use and high-intensity statin therapy among the cohort with the lowest degree of VHA utilization (i.e., < 50%). Interventions to increase statin use among veterans at high risk of cardiovascular events with lower degrees of VHA utilization should be explored. DISCLOSURES: This study was supported by a grant funded by the Department of Veterans Affairs' Health Services Research and Development Service and was undertaken at the Health Equity and Rural Outreach Center (HEROIC) at Ralph H. Johnson Veteran Affairs Medical Center, Charleston, SC. The authors report no potential conflicts of interest relevant to this article. This article represents the views of the authors and not those of the Medical University of South Carolina or Veteran Health Administration.