Comparative Effectiveness of Anticholinergic Agents for Lower Urinary Tract Symptoms.

BACKGROUND: Limited data from short-term clinical trials suggest efficacy advantages of solifenacin and fesoterodine over other anticholinergic agents in the treatment of lower urinary tract symptoms. OBJECTIVES: To (a) determine the real-world comparative effectiveness of newer anticholinergic agents for lower urinary tract symptoms, as assessed by 1-year persistence, and (b) identify patient factors independently associated with persistence. METHODS: We conducted a retrospective cohort study of U.S. veterans initiating newer anticholinergic therapy between October 2007 and August 2015. Multiple log-binomial regression was used to contrast 1-year persistence rates across anticholinergic agents while adjusting for measured confounders. Persistence was selected as a measure of effectiveness because nonpersistence is a common pathway encompassing inefficacy and intolerability, particularly in symptom-driven conditions. RESULTS: A total of 26,775 patients were included, of which 10,386 (38.8%) persisted with anticholinergic therapy at 1 year. Using long-acting tolterodine as the reference agent, superior persistence rates were observed for solifenacin (RR = 1.08, 95% CI = 1.03-1.13) and fesoterodine (RR = 1.25, 95% CI = 1.09-1.43), and a lower rate for short-acting tolterodine (RR = 0.90, 95% CI = 0.85-0.94). Patient factors associated with higher persistence rates included older age, male sex, and comorbidities such as multiple sclerosis, Parkinson's disease, and diabetes. CONCLUSIONS: Consistent with clinical trial reports, we found evidence for superior effectiveness of solifenacin and fesoterodine relative to other anti-cholinergics and for long-acting formulations over short-acting formulations. 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 (CDA 10-017). 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. The authors have no conflicts of interest. Study concept and design were contributed by all the authors. Shaw took the lead in data collection, along with Lund, and data interpretation was performed by Lund, Goodson, and Cantrell. The manuscript was written by Goodson, Cantrell, Lund, and Shaw and revised by Lund, Goodson, Cantrell, and Shaw.

Difference in Composite End Point of Readmission and Death Between Malnourished and Nonmalnourished Veterans Assessed Using Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition Clinical Characteristics.

BACKGROUND: Previous studies have demonstrated an association between malnutrition and poor outcomes. The primary objective of this study was to explore the difference in the composite end point of readmission rate or mortality rate between hospitalized veterans with and without malnutrition. MATERIALS AND METHODS: This was a retrospective chart review comparing veterans with malnutrition based on a modified version of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition consensus characteristics that used 5 of the 6 clinical characteristics to a matched control group of nonmalnourished veterans based on age, admitting service, and date of admission who were admitted between August 1, 2012, and December 1, 2014. Data were extracted from the medical record. Multivariate analysis was used to identify predictors of outcomes. RESULTS: In total, 404 patients were included in the final analysis. All end points were found to be statistically significant. The malnourished group was more likely to meet the composite end point (odds ratio [OR], 5.3), more likely to be readmitted within 30 days (OR, 3.4), more likely to die within 90 days of discharge (OR, 5.5), and more likely to have a length of stay >7 days (OR, 4.3) compared with the nonmalnourished group. Length of stay was significantly longer in the malnourished group, 9.80 (11.5) vs 4.38 (4.5) days. CONCLUSION: Malnutrition was an independent risk factor for readmission within 30 days or death within 90 days of discharge. Malnourished patients had higher rates of readmission, higher mortality rates, and longer lengths of stay and were more likely to be discharged to nursing homes.

Effect of selected clinical trial publication on adjunctive nonstatin medication prescribing in the Veterans Health Administration system.

PURPOSE: The question of whether publication of selected clinical trials is temporally followed by changes in prescribing of adjunctive lipid-lowering medications was evaluated. METHODS: In this retrospective preanalysis and postanalysis, Veterans Health Administration (VHA) patients 18 years or older who received a new or renewed order for any lipid-lowering medication between April 2, 2004, and September 2, 2014, were included. This period was chosen based on the publication dates of three trials investigating the efficacy of nonstatin medications: Simvastatin with or without Ezetimibe in Familial Hypercholesterolemia (ENHANCE, April 3, 2008), Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus (ACCORD Lipid, March 14, 2010), and Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy (AIM-HIGH, December 15, 2011). Annual prescribing rates for ezetimibe, fibrates, and niacin were analyzed for 4 years before and after the ENHANCE, ACCORD, and AIM-HIGH trial publication dates, respectively (3 years for niacin in AIM-HIGH) and reported as percent of patients in the cohort. RESULTS: Among patients receiving lipid-lowering medications, relatively low overall prescribing rates were observed for all three target medications. Prescribing rates for each medication decreased after its respective trial publication, with ezetimibe having the greatest change. CONCLUSION: Prescribing of fibrates, niacin, and ezetimibe in the VHA system decreased after the publication of landmark trials assessing their addition to a statin, consistent with the recommendations in the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline, which did not encourage routine use of adjunctive therapies to lower the risk of cardiovascular disease.

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.

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.

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%).

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.

Preemptive dose reduction of warfarin in patients initiating metronidazole.

BACKGROUND: The goal of this study was to determine if preemptive dose reduction (PDR) of warfarin is effective in maintaining therapeutic anticoagulation in patients initiating metronidazole. METHODS: This is a retrospective, single-center, cohort study in a pharmacist-managed anticoagulation clinic of a university affiliated Veteran's Affairs (VA) Medical Center. Subjects were anticoagulation patients initiating metronidazole between 1 January 2002 and 30 March 2009. At the time of metronidazole initiation, patients were managed with PDR of warfarin or no dose reduction. The primary outcome was the average change in International Normalized Ratio (INR) between patients that received PDR vs. those that did not. RESULTS: In total, 20 patients met inclusion criteria with seven patients receiving PDR at the time of initiation of metronidazole, whereas 13 did not. Patients managed with PDR and those that were not were similar in age (mean±SD 69.4±12.9 years vs. 72.1±9.9 years, p=0.61), mean baseline INR before metronidazole (2.58±0.49 vs. 2.57±0.66, p=0.98), and mean time to follow-up after initiation of metronidazole (5.6±2.9 days vs. 7.0±3.7 days, p=0.40), respectively. The primary outcome was statistically significant with a mean difference in INR of 1.28 (p=0.01) between patients manag-ed with PDR vs. those that were not. The mean preemptive warfarin dose reduction was 34.6%±13.4% which resulted in no significant increase in INR (p=0.61). Secondary outcomes including INR values >4.0 (0% vs. 46%, p=0.05), the average number of warfarin doses omitted (0.43±0.79 vs. 1.15±1.27, p=0.17), use of phytonadione or fresh frozen plasma, and rates of bleeding events were not significantly different be-tween groups. No thromboembolic events occurred during the 30 days following metronidazole therapy. CONCLUSIONS: In patients determined to be appropriate candidates for PDR, a 30%-35% reduction in mean daily warfarin dose was effective in maintaining therapeutic anticoagulation in patients started on concomitant metronidazole.

Atmospheric pressure changes and unexplained variability in INR measurements.

Changes in atmospheric pressure may influence hepatic blood flow and drug metabolism. Anecdotal experience suggests international normalized ratio (INR) variability may be temporally related to significant atmospheric pressure changes. We investigated this potential association in a large sample of patients with multiple INRs. This is a retrospective review of outpatient anticoagulation records from the Iowa City Veteran's Affairs Medical Center and affiliated outpatient clinics from October 1999 to July 2007. All patients, receiving at least one prescription for warfarin and INR at least 30 days or more from the date of the first warfarin prescription, were identified. INRs during periods of hospitalization and vitamin K use were excluded. Proximity analysis using geocoding of ZIP codes of identified patients to the nearest National Oceanic and Atmospheric Administration station was performed to assign atmospheric pressure with INR. Spearman's Rho and Pearson's correlation were used to evaluate atmospheric pressure and INR. Unique patients (1441) with 45 187 INRs were analyzed. When limited to nontherapeutic INRs following a previously therapeutic INR (1121 unique patients/5256 INRs), a small but clinically insignificant association between delta INR and delta atmospheric pressure was observed (r = -0.025; P = 0.038), but not for actual INR and atmospheric pressure (P = 0.06). Delta atmospheric pressure demonstrated greater variation during fall/winter months compared with spring/summer (0.23 vs. 0.15 inHg; P < 0.001); however, variability in INRs for the corresponding seasons was not significant (P = 0.136). No significant difference was detected in the proportions of nontherapeutic INRs among the different seasons (P = 0.371). No correlation was observed between atmospheric pressure changes and INR variability. These findings refute the anecdotal experience seen in our anticoagulation clinic.