Examining Hepatitis, A and B Vaccination, and HBV Reactivation Monitoring During Direct-Acting Antiviral Therapy for Hepatitis C.

The objective of this study was to examine Hepatitis A (HAV) and Hepatitis B (HBV) screening, and the risk of HBV reactivation during Hepatitis C (HCV) therapy with direct-acting antivirals (DAAs). A retrospective chart review was performed of patients treated with second generation DAA therapy from January 2014 to September 2016 at the Iowa City VA Healthcare System. In total 409 patients initiated HCV treatment, 308 (75%) and 241 (59%) were HAV and HBV vaccine eligible, respectively. Among those, 24 (8%) received a HAV vaccine, while only 20 (8%) received a HBV vaccine. Of these, 7 patients initiating an immunization in the clinic had record of completing the series. Further, 101 patients had a reactive Hepatitis B core Antibody indicating previous HBV infection, and 3 of these were tested for HBV reactivation during HCV therapy. Overall, the assessment found low rates of HAV and HBV vaccine administration, indicating missed opportunities for preventative care during HCV therapy. With the known risk of HBV reactivation with DAAs, the need for HAV and HBV screening is essential.

Mixed-methods evaluation of a telehealth collaborative care program for persons with HIV infection in a rural setting.

BACKGROUND: Delivery of comprehensive care for persons with human immunodeficiency virus (HIV) infection in rural and low prevalence settings presents many challenges. We developed and evaluated a telehealth collaborative care (TCC) program for persons with HIV in a rural area. OBJECTIVE: To determine the feasibility of TCC, and identify factors influencing implementation in rural settings. DESIGN: Mixed methods evaluation of a quality improvement program with pre-measures and post-measures. PATIENTS: Veterans with HIV infection in Iowa and Illinois. INTERVENTION: TCC integrated HIV specialty care delivered by clinical video telehealth, with primary care delivered by generalist providers, in seven Community Based Outpatient Clinics (CBOCs) serving rural areas. Principles guiding TCC design were: 1) clear delineation of specialty and primary care clinic roles in co-managed care; 2) creation of processes to improve care coordination between specialty and primary care teams; and 3) use of a patient registry for population management across sites. MEASURES: Veterans Affairs (VA) healthcare system performance measures for care for HIV infection and common comorbidities, patient travel time to obtain care, and patient satisfaction. Qualitative evaluation involved semi-structured telephone interviews with patients. KEY RESULTS: Thirty of 32 eligible patients chose TCC over traveling to the HIV clinic for all care. Among 24 patients in TCC during the June 2011-May 2012 evaluation period, median age was 54 (range, 40-79), most (96 %) were men, and median CD4 count was 707 cells/cm(3) (range, 233-1307). VA performance measures were met for > 90 % of TCC patients. Median yearly travel time decreased from 320 min per patient prior to TCC to 170 min during TCC (p < 0.001). Interview themes included: 1) overcoming privacy concerns during care in local primary care clinics; 2) tradeoffs between access, continuity, and care coordination; and 3) the role of specialist involvement in collaborative care. DISCUSSION: Telehealth Collaborative Care is a feasible approach to providing accessible and comprehensive care for persons with HIV in rural settings.

Sodium glucose cotransporter 2 inhibitors and gout risk: a sequence symmetry analysis.

OBJECTIVE: To examine the association between sodium-glucose cotransporter 2 inhibitors (SGLT2-I) and gout incidence in patients with diabetes is the objective. METHOD: National administrative data from the United States Veterans Health Administration were used to identify patients initiated on SGLT2-I from 2012 to 2020. Sequence symmetry analysis was performed to contrast the number of patients with incident gout within the year following SGLT2-I initiation to the number within the year preceding initiation. Exposure counterfactual analyses examined the relationship between potential therapeutic alternatives to SGLT2-I and risk for gout. RESULTS: The primary outcome of incident gout was observed in 441 patients preceding SGLT2-I initiation and 273 patients following SGTL2-I (symmetry ratio (SR) = 0.62; 95% CI: 0.53-0.72). This finding remained consistent across multiple sensitivity analyses. A reduction in gout incidence was also observed in exposure counterfactual cohorts initiating dipeptidyl peptidase-4 inhibitor (SR = 0.67; 95% CI: 0.63-0.72) and thiazolidinediones (SR = 0.72; 95% CI: 0.65-0.79), but not glucagon-like peptide-1 receptor agonist (GLP1-RA) (SR = 0.93; 95% CI: 0.77-1.12). CONCLUSIONS: The risk for incident gout was significantly reduced following SGLT2-I initiation. GLP1-RA had minimal to no impact on gout risk. Our findings support pleiotropic benefits of SGLT2-I use in patients with diabetes at elevated risk for gout. Key points • Early studies suggest SGLT2-inhibitors may decrease risk for gout • Our sequence symmetry analysis confirmed this observation • DPP4s and thiazolidinediones were also associated with lower gout risk • SLGT2 inhibitors may be beneficial in patients with diabetes at risk for gout.

Clinical Impact of GLP-1 receptor agonists in veterans receiving basal-bolus insulin.

BACKGROUND: In 2017, an estimated 7.4 million Americans used insulin to treat diabetes. Insulin is proven to lower A1c but can result in hypoglycemia and weight gain. Combining insulin with a glucagon-like peptide-1 receptor agonist (GLP-1-RA) may provide additional blood glucose control while limiting undesirable effects including weight gain. OBJECTIVE: To characterize the clinical impact of adding a GLP-1-RA to a basal-bolus insulin regimen in patients with type 2 diabetes. METHODS: This retrospective observational study used national Veteran's Health Administration data to identify patients with an existing basal-bolus insulin regimen who initiated a GLP-1-RA between January 1, 2005 and December 31, 2017. A1c, insulin total daily dose (TDD), and weight were collected at GLP-1-RA initiation (baseline), 3-, 6-, and 12-month time points and then analyzed using an intent-to-treat approach with the last observation carried forward. Decreases in A1c ≥ 0.5% and weight ≥2 kg were deemed clinically significant. RESULTS: Among 7651 patients initiating GLP-1-RA therapy, mean A1c had a clinically significant decline at 3, 6, and 12 months by -0.5%, -0.7%, and -0.7%, respectively, from a mean baseline of 9%. Patients with lower baseline A1c levels did not have clinically significant changes in A1c, whereas patients with baseline A1c ≥9% had more clinically significant declines. Insulin TDD decreased by -32, -38, and -42 units/day at 3, 6, and 12 months, respectively, where the mean decrease in insulin TDD at 12 months was 79 units/day among patients who discontinued bolus insulin (52.3%) compared with a mean decrease of 2 units/day among those who continued bolus insulin. Mean weight reductions at 3, 6, and 12 months were -1.2, -2.3, and -2.9 kg, respectively, from a mean baseline of 120.6 kg. CONCLUSION: Combining a GLP-1-RA with basal-bolus insulin had a clinically significant improvement on blood glucose control, lowered insulin TDD, and reduced weight. These outcomes were achieved within 3 to 6 months following GLP-1-RA initiation and were maintained through 1 year.

Evaluation of the metformin initiation rate in veterans with newly identified type 2 diabetes.

BACKGROUND: An estimated 35 million individuals in the United States have diabetes. The American Diabetes Association recommends metformin as first-line pharmacologic treatment. The primary objective of this study was to evaluate the metformin initiation rate in veterans with recently identified type 2 diabetes. METHODS: Veterans with new onset type 2 diabetes were identified using National Veterans Health Administration Data. Retrospective information was obtained from those with a first A1C ≥ 6.5% (48 mmol/mol) between 2013 and 2018. Veterans with at least one additional A1C < 6.5% (48 mmol/mol) documented in the three years prior to the A1C diagnostic for diabetes were included in the analysis. RESULTS: A total of 144,180 veterans were included. Of those, 45,776 (31.7%) were started on metformin within one year of diabetes diagnosis. The median time to metformin initiation was 12 days and median time to initiation of any anti-hyperglycemic was 11 days. Approximately 16,000 veterans were referred for lifestyle interventions within 90 days. CONCLUSION: Metformin initiation occurred in fewer patients than expected given metformin is a generic, well-tolerated medication recommended as first-line pharmacologic treatment option regardless of A1C. Further studies are needed to assess the barriers of initiating metformin at time of diabetes diagnosis.

Evaluation of the HealthImpact Diabetes Risk Model in the Veterans Health Administration.

BACKGROUND: HealthImpact is a novel algorithm using administrative health care data to stratify patients according to risk for incident diabetes. OBJECTIVES: To (a) independently assess the predictive validity of HealthImpact and (b) explore its utility in diabetes screening within a nationally integrated health care system. METHODS: National Veterans Health Administration data were used to create 2 cohorts. The replication cohort included patients without diagnosed diabetes as of October 1, 2012, to determine if HealthImpact scores were significantly associated with diabetes (type 1 or 2) incidence within the subsequent 3 years. The utility cohort included patients without diagnosed diabetes as of August 1, 2015, and assessed diabetes screening rates in the 2 years surrounding this index date, stratified by HealthImpact scores. RESULTS: The 3-year incidence of diabetes in the replication cohort (n = 3,287,240) was 9.1%. Of 100,617 (3.1%) patients with HealthImpact scores > 90, 30,028 developed diabetes, yielding a positive predictive value of 29.8%. These patients accounted for 9.9% of all incident diabetes cases (sensitivity). Sensitivity and negative predictive value improved with descending HealthImpact threshold scores (e.g., > 75, > 50), whereas specificity and positive predictive value declined. Of 3,499,406 patients in the utility cohort, 85.3% received either a blood glucose or hemoglobin A1c test during the 2-year observation period. Among 101,355 patients with a HealthImpact score > 90, nearly all (98.3%) were screened, and 86.3% had an A1c test. CONCLUSIONS: Our independent analysis corroborates the validity of HealthImpact in stratifying patients according to diabetes risk. However, its practical utility to enhance diabetes screening in a real-world clinical environment will be strongly dependent on the pattern and frequency of existing screening practices. DISCLOSURES: This work was supported by the Iowa City VA Health Care System and by the Department of Veterans Affairs, Office of Research and Development, Health Services Research and Development Service (Lund, CIN 13-412). The authors have no conflicts of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government.

Adding glucose-lowering agents delays insulin initiation and prolongs hyperglycemia.

OBJECTIVES: Nine classes of glucose-lowering agents (GLAs) are available for patients with type 2 diabetes prior to starting insulin. This study's aim was to determine if the number of GLAs is associated with a difference in glycated hemoglobin (A1C) at insulin initiation in the US Department of Veterans Affairs Health Care System (VAHCS). STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort with national Veterans Health Administration data was created. Veterans with type 2 diabetes and first insulin prescription filled in the VAHCS between January 1, 2009, and August 28, 2013, were identified. Included veterans refilled insulin within the first year, had an A1C > 7% (53 mmol/mol) at least 60 days prior to insulin initiation, and received a GLA within 6 months prior to insulin. Veterans were grouped into 4 cohorts according to the number of GLAs used. RESULTS: A total of 90,497 veterans with type 2 diabetes met inclusion criteria. Insulin was initiated at a mean A1C of 9.9% (85 mmol/mol). The mean A1Cs prior to insulin for 1, 2, 3, or > 3 GLAs were 10.3% (89 mmol/mol), 9.9% (85 mmol/mol), 9.6% (81 mmol/mol), and 9.6% (81 mmol/mol), respectively. Months to insulin increased with the number of GLA trials and prolonged the time veterans were exposed to A1C > 8% (64 mmol/mol). CONCLUSIONS: Multiple glucose-lowering drug classes are associated with a numerical, but not a clinical, difference in A1C at insulin initiation in the closed formulary of the VAHCS.

Prevalence of achievement of A1c, blood pressure, and cholesterol (ABC) goal in veterans with diabetes.

BACKGROUND: The "ABCs of Diabetes" are defined as hemoglobin A1c < 7.0%, blood pressure < 130/80 millimeters mercury (mm Hg), and lowdensity lipoprotein cholesterol (LDL-C) < 100 milligrams per deciliter (mg per dL). Assessments of 3-part goal attainment of A1c, blood pressure, and cholesterol have been reported using data from the National Health and Nutrition Examination Survey (NHANES) for several time periods (e.g., 1988-1994, 1999-2000, 1999-2002, and 2003-2004), Look Action for Health in Diabetes (Look AHEAD, 2001-2004), and community-based endocrinology practice (CBEP, 2000-2004). In 2002, an unpublished analysis of data from 2001-2002 at the Iowa City Veterans Affairs (ICVA) Medical Center found less than 50% of patients met each of the 3 individual goals. In the 5 years following the 2001-2002 assessment, the care for veterans with diabetes at the ICVA was enhanced to include (a) an increased number of diabetes classes and clinics, (b) implementation of the diabetes Care Coordination/Home Telehealth (CCHT) program, and (c) clinical reminders for diabetes performance measures that were added to the electronic medical record (EMR). OBJECTIVES: To (a) describe the prevalence of veterans meeting the ABC goals of diabetes in 1 VA medical center; (b) differentiate the proportion of diabetes patients who met the individual targets for A1c, blood pressure, and LDL-C and compare the results for 2008 through September 2009 with the earlier data from this facility (2001-2002); and (c) examine results reported previously in the literature for NHANES, Look AHEAD, and CBEP data sources. METHODS: Single-center, retrospective analysis of veterans at the ICVA for dates of service from January 1, 2008, through September 30, 2009, who (a) filled at least 1 prescription for an antidiabetic medication and (b) had each of the 3 biomarker values recorded in the EMR for A1c, blood pressure, and LDL-C after the antidiabetic prescription fill date. RESULTS: Of the 5,426 (97.6% male) patients meeting inclusion criteria in 2008-2009, 17.3% (n = 936) achieved the 3-part ABC goal. In this managed care setting, achievement of the 3-part ABC goal surpassed the proportions reported in previous studies in NHANES data (5.2% in 1988-1994, 7.3% in 1999-2000, 7.0% in 1999-2002, 13.2% in 2003-2004), and 10.1% in Look AHEAD 2001-2004, but fell short of the 22.0% reported in CBEP 2000- 2004. When compared with the 2001-2002 results at ICVA, the proportion of patients achieving the individual A1c goal in 2008-2009 increased by 10.8 percentage points (from 43.2% to 54.0%), 12.6 percentage points for blood pressure (from 29.2% to 41.8%), and 17.1 percentage points for LDL-C (from 49.5% to 66.6%, P < 0.001) for the 3 individual comparisons. CONCLUSIONS: The proportion of patients achieving each of the 3 goals for A1c, blood pressure, and LDL-C improved significantly in 2008-2009 compared with the 2001-2002 assessment in this medical center, following implementation of yearly clinical reminders for diabetes care, enhanced patient education, and other program changes that included home-based telephone monitoring with diabetes case management for some patients. Achievement of the 3-part ABC goal in 2008-2009 (17.3%) surpassed 5 assessments reported in the literature but was lower than the CBEP (2000- 2004) performance (22.0%).

Glycemic control and hypoglycemia in Veterans Health Administration patients converted from glyburide to glipizide.

BACKGROUND: In 2009, the Veterans Health Administration (VHA) released a national bulletin regarding the risk of hypoglycemia associated with the use of glyburide in elderly patients with renal dysfunction. Providers were encouraged to avoid glyburide and use glipizide in patients with a calculated creatinine clearance (CrCl) of less than 50 mL per minute. Since this initiative, many veterans were converted by their providers from glyburide to glipizide regardless of renal impairment. OBJECTIVES: To (a) identify whether hemoglobin A1c remained equivalent in patients converted from glyburide to glipizide, (b) evaluate the prevalence of hypoglycemia during treatment with glyburide or glipizide, (c) compare change in glycemic control for renally impaired versus nonimpaired patients, and (d) analyze dosage conversion ratios selected by providers and measures of patient follow-up after conversion including time until A1c measurement and number of glipizide dose titrations. METHODS: This was a single-center, retrospective analysis of veterans converted from glyburide to glipizide from January 1, 2008, through May 31, 2010, who had documented A1c values concurrent with glyburide and glipizide use. A 2-sided equivalence analysis was used for the primary outcome. Equivalence was defined as a change in mean A1c of ± 0.2. Hypoglycemia was defined as blood glucose of less than 70 mg per dL, symptoms of hypoglycemia, or hypoglycemia that led to a fall, loss of consciousness, emergency room visit, hospitalization, or death. The pre- to post-conversion change in rates of hypoglycemia was tested for significance using a McNemar's test. RESULTS: In the 141 (99.3% male, 53.9% CrCl less than 50 mL per minute, mean age = 74.0 years) patients meeting inclusion criteria between 2008-2010, the average change in A1c (+ 0.34) was nonequivalent after conversion from glyburide to glipizide (7.08% vs. 7.42%, respectively). Hypoglycemia occurred more frequently during treatment with glyburide than glipizide (31.2% vs. 12.8%, respectively, P less than 0.001). Mean dose conversion ratios were consistent with VHA recommendations (1 mg per day glyburide = 1.26- 1.55 mg per day glipizide). CONCLUSIONS: Conversion from glyburide to glipizide was associated with an increase in A1c, but the incidence of hypoglycemia was reduced. Results of this study are consistent with the recommendation of the American Diabetes Association and European Association for the Study of Diabetes to use second-generation sulfonylureas other than glyburide. Patients converted to glipizide should be monitored closely to adjust therapy as appropriate to maintain glycemic control.

Glucose control in patients with type 2 diabetes based on frequency of insulin glargine administration.

Glucose control and predictors of a switch from once to twice daily administration of insulin glargine in patients with type 2 diabetes was investigated. A mean decrease in %A1c of 0.52+/-0.12 (p=0.14) resulted, indicating clinical relevance. Daily dose was the only significant predictor of twice daily therapy.

Capecitabine-warfarin interaction.

OBJECTIVE: To report a case of concomitant warfarin therapy with consecutive cycles of capecitabine therapy, providing time of onset, magnitude, and assessment of the interaction. CASE SUMMARY: A 59-year-old man receiving chronic warfarin therapy for a mechanical mitral valve replacement was diagnosed with stage IV metastatic colon cancer. He was started on capecitabine/irinotecan after his cancer progressed with fluorouracil/leucovorin and the FOLFOX 6 regimen (oxaliplatin, leucovorin, and continuous fluorouracil infusion). He received 3 consecutive cycles of capecitabine/irinotecan with concomitant oral anticoagulation and, with each cycle, the warfarin dose was reduced. Over the course of these 3 cycles, the total weekly dose of warfarin was reduced by >85%. DISCUSSION: The capecitabine-warfarin interaction is clinically significant, requiring a black box warning in the package insert. The mechanism of action for the interaction is not clear, but may be related to down-regulation of CYP2C9 by capecitabine or its metabolites or a pharmacodynamic interaction with warfarin. A common response to this interaction, as discussed in previously published case reports, is the discontinuation of warfarin, capecitabine, or both. In this case, the Naranjo probability scale indicates a highly probable drug interaction between warfarin and capecitabine. CONCLUSIONS: As more patients require anticoagulation, and as chemotherapy agents such as capecitabine become available, the likelihood for these drug interactions increases. In our patient, close monitoring of therapy allowed successful use of warfarin and capecitabine.