Grant H. Skrepnek

Persistence, Adherence, and Risk of Discontinuation Associated with Commonly Prescribed Antihypertensive Drug Monotherapies

Objective: To assess 1-year persistence and adherence with monotherapy using the most commonly dispensed individual agent in 4 antihypertensive drug classes: hydrochlorothiazide (HCTZ), amlodipine, lisinopril, or valsartan. Design: Retrospective, longitudinal analysis of initial prescriptions during 2001 to 2002 from a nationwide administrative claims database representing 11 million covered lives in the United States. Measurements: Drug utilization following initiation. Cox proportional hazards regression models controlled for demographics, case-mix, and concomitant treatments. Results: Records for 60,685 subjects were included: HCTZ (n = 18,713), amlodipine (n = 11,520), lisinopril (n = 21,138), or valsartan (n = 9314). Over 1 year, 31% to 44% of subjects utilized no treatment for at least 60 days. Medication possession ratio (MPR) and adherence measures ranged from 73% to 90%. Valsartan was associated with significantly (P < .001) more favorable measures of persistence, length of therapy, time to discontinuation, MPR, and risk of discontinuation, compared with HCTZ, amlodipine, or lisinopril. The risk of discontinuation was 53%, 32%, and 14% greater for HCTZ, amlodipine, and lisinopril, respectively, versus valsartan (all comparisons P < .001). Conclusion: Among antihypertensive agents studied, valsartan was associated with the most favorable utilization patterns. Health care providers and systems should evaluate the use of antihypertensive drugs within their populations to identify and manage treatment discontinuation.

Acute Exacerbations of COPD in the United States: Inpatient Burden and Predictors of Costs and Mortality

Abstract Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a leading cause of hospitalizations in the United States and the major cost driver of COPD. This study determined the national inpatient burden of AECOPD and assessed the association of co-morbidities and hospital characteristics with inpatient costs and mortality. Discharge records from the Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample for 2006 was utilized. Outcomes of costs and mortality were assessed for AECOPD hospitalizations in cases ≥40 years of age. Multivariate regression analyses using a generalized linear model framework were conducted to determine predictors of inpatient costs and mortality controlling for patient demographics, primary payer, co-morbidity index, length of stay, hospital region, mechanical ventilation, and admission period. Overall, 1,254,703 hospitalizations for AECOPD were observed with mean costs of

Pharmacist workload and pharmacy characteristics associated with the dispensing of potentially clinically important drug-drug interactions

9545(±12,700) and total costs of

Prescribers' knowledge of and sources of information for potential drug-drug interactions: a postal survey of US prescribers.

11.9 billion. In-hospital mortality was 4.3% (N = 53,748). Discharges averaged 70.6 (±11.9) years of age. The majority were female (52.8%) and of white race (83.6% of reported race). Several co-morbidities were significantly associated with both costs and mortality (p < 0.001): acute myocardial infarction; congestive heart failure; cerebrovascular disease; lung cancer; cardiac arrhythmias; pulmonary circulation disorders; and weight loss. Significantly higher costs (p < 0.001) were associated with large and urban hospitals. The importance of co-morbidities in AECOPD is indicated in their association with prognosis and inpatient costs. Future research should determine if better management of these conditions can favorably impact the COPD disease burden.

Escitalopram versus sertraline in the treatment of major depressive disorder: a randomized clinical trial*

Background:Drug-drug interactions (DDIs) are preventable medical errors, yet exposure to DDIs continues despite systems that are designed to prevent such exposures. The purpose of this study was to examine pharmacy characteristics that may be associated with dispensed potential DDIs. Methods:This study combined survey data from community pharmacies in 18 metropolitan statistical areas with pharmacy claims submitted to 4 pharmacy benefit managers (PBMs) over a 3-month period from January 1, 2003 to March 31, 2003. Pharmacy characteristics of interest included prescription volume, the number of full-time equivalent pharmacists and pharmacy staff, computer software programs, and the ability to modify those programs with respect to DDI alerts, the use of technologies to assist in receiving, filling and dispensing medication orders, and prescription volume. The dependent variable in this study was the rate of dispensed medications that may interact. Results:A total of 672 pharmacies were included in the analysis. On average (±SD), the respondents filled 1375 ± 691 prescriptions per week, submitted 17,948 ± 23,889 pharmacy claims to the participating PBMs, had 1.2 ± 0.3 full-time equivalent pharmacists per hour open, and 545 (81%) were affiliated with a chain drug store organization. Factors significantly related to an increased risk of dispensing a potential DDI included pharmacist workload (odds ratio [OR] 1.03; 95% confidence interval [CI] 1.028–1.048), pharmacy staffing (OR 1.10; 95% CI: 1.09–1.11), and various technologies (eg, sophisticated telephone systems, internet receipt of orders, and refill requests) that assist with order processing, and the ability to modify DDI alert-screening sensitivity and detailed pharmacological information about DDIs. Conclusions:This study found that there was an increase in the risk of dispensing a potential DDI with higher pharmacist and pharmacy workload, use of specific automation, and dispensing software programs providing alerts and clinical information.

Cost-Efficacy of Imatinib versus Allogeneic Bone Marrow Transplantation with a Matched Unrelated Donor in the Treatment of Chronic Myelogenous Leukemia: A Decision-Analytic Approach

AbstractBackground: Given the high prevalence of medication use in the US, the risk of drug-drug interactions (DDIs) and potential for patient harm is of concern. Despite the rise in technologies to identify potential DDIs, the ability of physicians and other prescribers to recognize potential DDIs is essential to reduce their occurrence. The objectives of this study were to assess prescribers’ ability to recognize potential clinically significant DDIs and to examine the sources of information they use to identify potential DDIs and prescribers’ opinions on the usefulness of various DDI information sources. Methods: A postal questionnaire was developed to assess prescriber knowledge of medications that may interact and prescribers’ usual sources of DDI information. Recipients were asked to classify 14 drug pairs as ‘contraindicated’, ‘may be used together but with monitoring’ or ‘no interaction’. A response option of ‘not sure’ was also provided. The questionnaires were sent to a national sample of 12 500 prescribers based on past history of prescribing drugs associated with known potential for DDI, who were identified using data from a pharmacy benefit manager covering over 50 million individuals. Results: Usable questionnaires were obtained from 950 prescribers. The percentage of prescribers who correctly classified specific drug pairs ranged from 18.2% for warfarin and cimetidine to 81.2% for paracetamol (acetaminophen) with codeine and amoxicillin, with 42.7% of all combinations classified correctly. The number of drug pairs correctly classified by the prescribers ranged from 0 to 13. For half of the drug pairs over one-third of the respondents answered ‘not sure’; among those drug pairs, two were contraindicated. When asked what source was used to learn more about a potential DDI, a quarter of the prescribers reported using personal digital assistants and another quarter used printed material. The majority of the prescribers (68.4%) reported that they were usually informed by pharmacists about their patients’ potential exposure to DDIs. Compared with the prescribers who used other sources, those who used computerized DDI alerts as their usual source of DDI information consistently gave a lower rating score to the five statements that assessed the usefulness of the information. Conclusion: This study suggests that prescribers’ knowledge of potential clinically significant DDIs is generally poor. These findings are supported by other research and emphasize the need to develop systems that alert prescribers about potential interactions that are clinically relevant. Physicians most commonly reported learning about potential DDIs from pharmacists, suggesting further work is needed to improve the drug-prescribing process to identify potential safety issues earlier in the medication use process.

Effect of epidural analgesia on postoperative complications following pancreaticoduodenectomy

ABSTRACT Objective: This trial was conducted to compare the efficacy and tolerability of a fixed dose of escitalopram 10 mg/day with sertraline optimally dosed within its recommended dose range (50–200 mg/day) for the treatment of major depressive disorder. Methods: In this multicenter trial, depressed patients (DSM‑IV defined; baseline Montgomery–Asberg Depression Rating Scale [MADRS] ≥ 22) aged 18–80 years were randomly assigned to 8 weeks of double-blind treatment with escitalopram (10 mg/day) or sertraline (50–200 mg/day) following a 1‑week single-blind placebo lead-in period. There was no placebo comparison arm. Sertraline was initiated at 50 mg/day, and could be increased by 50 mg/day at weekly intervals based on clinical need and tolerability at the lower dose level. The blind was maintained with matching double-blind placebo capsules for the escitalopram group. Change from baseline to endpoint in MADRS total score (last observation carried forward) was the primary efficacy measure. Results: A total of 212 patients received double-blind medication. At week 8, the mean sertraline dosage was 144 mg/day (median = 150 mg/day). Mean changes from baseline to endpoint in MADRS scores were –19.1 and –18.4 for the escitalopram and sertraline groups, respectively. At endpoint, 75% and 70% of escitalopram- and sertraline-treated patients, respectively, were responders (≥ 50% improvement from baseline in mean MADRS scores). Both treatments were generally well tolerated; only 2% and 4% of patients prematurely discontinued escitalopram and sertraline treatment, respectively, due to adverse events. Conclusion: No differences in efficacy were observed for fixed-dose escitalopram 10 mg/day and sertraline flexibly dosed from 50–200 mg/day. At these doses, both escitalopram and sertraline were generally well tolerated.

A Diabetic Emergency One Million Feet Long: Disparities and Burdens of Illness among Diabetic Foot Ulcer Cases within Emergency Departments in the United States, 2006–2010

Study Objective. To develop and populate a decision‐analytic model for comparing the 2‐year cost and efficacy of imatinib versus allogeneic bone marrow transplantation (BMT) with a matched unrelated donor in the treatment of a 35‐year‐old man with newly diagnosed, Philadelphia chromosome—positive (Ph[+]) chronic myelogenous leukemia (CML) in the chronic phase.

Econometric approaches in evaluating costs and outcomes within pharmacoeconomic analyses

BACKGROUND The purpose of this study was to evaluate the effect of epidural analgesia use on postoperative complications in patients undergoing pancreaticoduodenectomy. METHODS This retrospective cohort study used the 2009 Nationwide Inpatient Sample from the Agency for Healthcare Research and Quality. Patients who underwent pancreaticoduodenectomy were grouped on the basis of whether they received epidural analgesia. The effect of epidural use on the composite end point of major complications including death was investigated using a generalized linear model. RESULTS Overall, 8,610 cases of pancreaticoduodenectomy occurred within the United States in 2009, and 11.0% of these patients received epidural analgesia. After controlling for various potential confounders, results of the multivariate regression indicated that epidural analgesia use was associated with lower odds of composite complications including death (odds ratio, .61; 95% confidence interval, .37-.99; P = .044). CONCLUSIONS In patients who underwent pancreaticoduodenectomy, epidural analgesia was associated with significantly lower postoperative composite complications.

Cost–utility comparison of escitalopram and sertraline in the treatment of major depressive disorder

Objectives To evaluate the magnitude and impact of diabetic foot ulcers (DFUs) in emergency department (ED) settings from 2006–2010 in the United States (US). Methods This cross-sectional study utilized Agency for Healthcare Research and Quality (AHRQ) Healthcare Cost and Utilization Project (HCUP) National Emergency Department Sample (NEDS) discharge records of ED cases among persons ≥18 years with any-listed diagnosis of DFUs. Multivariable analyses were conducted for clinical outcomes of patient disposition from the ED and economic outcomes of charges and lengths of stay based upon patient demographic and socioeconomic factors, hospital characteristics, and comorbid disease states. Results Overall, 1,019,861 cases of diabetic foot complications presented to EDs in the US from 2006–2010, comprising 1.9% of the 54.2 million total diabetes cases. The mean patient age was 62.5 years and 59.4% were men. The national bill was