Eli Korner

Improving Prescribing Safety in Patients with Renal Insufficiency in the Ambulatory Setting: The Drug Renal Alert Pharmacy (DRAP) Program

Study Objective. To determine whether a computerized Drug Renal Alert Pharmacy (DRAP) program could decrease the rate of medication errors in drug selection or dosing for 15 target drugs in patients with renal insufficiency.

Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C: Results from a US database of over 45 000 HCV-infected, evaluated patients

Chronic hepatitis C (HCV) treatment with pegylated‐interferon (PEG‐IFN)/ribavirin (RBV) is often limited by preexisting medical, psychiatric and psychosocial contraindications. However, limited data exist in general patient populations.

Hepatitis C virus therapy is associated with lower health care costs not only in noncirrhotic patients but also in patients with end-stage liver disease

The effect of anti‐viral treatment on downstream costs for hepatitis C virus (HCV)‐infected patients is unknown.

Painful diabetic peripheral neuropathy in a managed care setting: patient identification, prevalence estimates, and pharmacy utilization patterns.

The objectives of this study were to validate an algorithm for identifying patients with painful diabetic peripheral neuropathy (pDPN) and demonstrate its practical applications. Using the Kaiser Permanente Colorado Diabetes Registry, an algorithm was developed with selected ICD-9 diagnosis codes combined with automated pharmacy data for medications prescribed for pDPN symptoms. Medical records were reviewed to confirm pDPN presence and to inform algorithm refinement. Prevalence was estimated with a numerator of members with diabetes who had inclusion but no exclusion codes in 2003 (Method 1) and with a numerator of diabetes patients with inclusion codes between 1998 and 2003 who had no subsequent exclusion codes and who remained members in 2003 (Method 2); the denominator was all members with diabetes in 2003. Medication utilization was compared between patients with and without pDPN. A total of 19,577 members with diabetes were identified; 2612 met initial inclusion criteria. Medical record review (n = 298) demonstrated sensitivity of 94%, specificity of 55%, and positive predictive value (PPV) of 64%. Inclusion criteria were modified and pharmacy data eliminated. The revised algorithm identified 1754 additional patients meeting inclusion criteria. Medical record review (n = 190) demonstrated sensitivity of 99%, specificity of 49%, and PPV of 79%. Using the validated algorithm, pDPN prevalence was 113 (Method 1) and 208 (Method 2) per 1000 persons with diabetes. Significant differences were observed in medication prescriptions between patients with and without pDPN. Estimated pDPN prevalence among persons with diabetes was 11%-21% and pDPN patients had greater utilization of selected medications than those without pDPN. Identifying patients with pDPN is a fundamental step for improving disease management and understanding the economic impact of pDPN.

High rates of early treatment discontinuation in hepatitis C-infected US veterans

BackgroundPatients with chronic hepatitis C (HCV) frequently discontinued dual therapy with pegylated interferon alfa (Peg-IFN) plus ribavirin (RBV) before reaching the recommended duration of 48 or 24 weeks for genotypes (G) 1/4 or 2/3, respectively. We quantified rates of discontinuation despite efficacy (non-LOE) versus lack of efficacy (LOE) versus discontinuation for unknown reasons in a national database of United States veterans.MethodsWe identified a population-based cohort of U.S. veterans with encounters from 2004 through 2009 who had lab-confirmed HCV infection and initiated therapy with Peg-IFN plus RBV in Veterans Health Administration medical centers. Pharmacy data were used to determine therapy duration, defined as the sum of Peg-IFN days supplied. Patients “discontinued” if they failed to receive at least 44 (G1/4) or 20 weeks (G2/3) of therapy. We classified discontinuations as due to non-LOE, LOE, or unknown reasons using a classification rule based on treatment duration and laboratory confirmed response.ResultsOf 321,238 diagnosed HCV patients during the evaluation period, 9.7% initiated therapy and 6.4% met all other inclusion criteria. 54.9% of patients discontinued early; of these, 41.2% discontinued due to non-LOE reasons, 12.5% discontinued for LOE reasons, and 46.3% discontinued for unknown reasons. Among non-LOE discontinuers, most (60.1%) discontinued in the first 4 weeks of therapy, which constitutes 13.6% of all treated patients.ConclusionsWe observed a high proportion of early discontinuations with dual-therapy regimens in a national cohort of HCV-infected veterans. If this trend persists in the triple-therapy era, then efforts must be undertaken to improve adherence.

Predictors of Early Discontinuation of Pegylated Interferon for Reasons Other Than Lack of Efficacy in United States Veterans With Chronic Hepatitis C.

During the dual-therapy era, many patients with chronic hepatitis C discontinued therapy for reasons other than lack of efficacy (non-LOE). We determined whether selected patient characteristics predicted non-LOE discontinuation using national databases of U.S. veterans with Genotypes 1–4. We identified U.S. veterans in the Veterans Health Administration system in 2004–2009 who had hepatitis C-confirming RNA laboratory results and initiated therapy with pegylated interferon and ribavirin. We used a rule to classify patients who discontinued pegylated interferon early, based on pharmacy refill and viral response data. Multivariate Cox regression was used to identify predictors of non-LOE discontinuation. Of 321,238 patients with a hepatitis C International Classification of Diseases, Ninth Revision, code, 15,297 (4.8%) met all inclusion criteria. Non-LOE discontinuers comprised 30.3% of patients. For Genotypes 1–4, the predictors (adjusted hazard ratio) of greatest magnitude were comorbidities of myocardial infarction/congestive heart failure (1.36), renal disease (1.34), and platelets 100/mm3 or more (1.38). For Genotypes 2 and 3, predictors of greatest magnitude were Black race (1.30), myocardial infarction/congestive heart failure (1.84), albumin 3.5 mg/dl or more (1.65), sleep aid use (1.32), and poor persistence with antidepressants (1.31) and antihypertensive agents (1.37). Our study suggests that many host factors may have contributed to non-LOE dual-therapy discontinuation in veterans and may possibly predict non-LOE discontinuation in triple therapy.

The Association of Cytopenias and Weight Loss with Hepatitis C Virus Virologic Response in HIV/HCV-Coinfected Patients Treated with PEG-IFN and RBV

Background: Pegylated interferon (PEG-IFN)/ribavirin (RBV)-related cytopenias have been associated with improved virological outcomes among hepatitis C virus (HCV)-monoinfected patients. This analysis evaluated PEG-IFN/RBV-related cytopenias with virological responses among HIV/HCV-coinfected patients. Methods: Pooled data from PARADIGM and AIDS Pegasys Ribavirin International CO-infection Trial (APRICOT) trials of HIV/HCV-infected patients treated with PEG-IFN/RBV. Virologic response was categorized as HCV RNA detectable (end of treatment nonresponders [ET-NR]) or nondetectable (end of treatment responders [ETR]). Declines in hemoglobin (Hgb), platelets, neutrophils, lymphocytes, and weight between the groups were compared via analysis of covariance and Cochran-Mantel-Haenszel test. Results: A total of 474 patients, 291 ET-NR and 183 ETR (67 relapsers, 116 with sustained virologic response), 81% male, 52% Caucasian, 88% noncirrhotic, and 67% nondetectable HIV. The ETR experienced greater Hgb declines (≥3.0 g/dL) from baseline (73.8% versus 55.0%; P < .0001), neutrophils ≤1 and ≤ 0.5 × 109/L (66.1% versus 56.4%; P = .0334 and 42.6% versus 33.3%; P = .0312, respectively), and lymphocytes ≤1.5 and ≤0.5 × 109/L (99.5% versus 87.6%; P < .0001 and 24.6% versus 14.9%; P =.0079, respectively). Conclusions: The HIV/HCV-coinfected patients with ETR experienced greater declines in Hgb, neutrophils, and lymphocytes than the ET-NR patients.

Predicting Discontinuation of Pegylated Interferon as a Result of Lack of Efficacy in United States Veterans With Chronic Hepatitis C on Dual Therapy

Background: Many patients with chronic hepatitis C virus (HCV) being treated with pegylated interferon (peg-IFN) plus ribavirin (RBV) do not respond to therapy and do not clear the virus. Standard of care during the era of dual therapy was to discontinue the patient’s therapy based on insufficient decreases in viral load after 12 and/or 24 weeks on therapy. Objectives: We identified patient characteristics that were significant predictors of discontinuation as a result of lack of efficacy (LOE) in a national database of US veterans with genotypes 1 and 4. Methods: We identified US veterans who received care at Veterans Affairs medical centers in 2004-2009 and who had lab-confirmed HCV diagnoses and initiated therapy with peg-IFN plus RBV. Patients who discontinued therapy early were classified as either LOE or non-LOE discontinuers based on pharmacy refill patterns and laboratory response data. Predictors of LOE discontinuation were identified using univariate and multivariable Cox proportional hazards modeling. Results: Of 321 238 HCV patients with an ICD-9 diagnosis code, 31 215 (9.7%) initiated dual therapy with peg-IFN plus RBV, and 10 333 (3.2%) met all inclusion criteria and were included in the analysis. Overall, 13.6% of the cohort was classified as LOE. Significant predictors of LOE discontinuation included treatment for drug abuse (hazard ratio [HR] = 2.18), age >65 years (HR = 1.75), antiretroviral therapy for HIV (HR = 1.48), black race (HR = 1.47), platelet count >100/mm3 (HR = 1.46), and drug therapy for insomnia (HR = 1.40). Conclusions: We identified risk factors for discontinuation caused by LOE. Future work should focus on determining whether these characteristics are also predictive of triple-therapy LOE discontinuations.

Commentary: Absolute and relative contraindications to pegylated-interferon or ribavirin in the US general patient population with chronic hepatitis C - Authors' reply

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