Kristin Knippenberg

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.

Fracture Rates and Bone Density Among Postmenopausal Veteran and Non-Veteran Women From the Women’s Health Initiative

PURPOSE OF THE STUDY Postmenopausal osteoporosis can impact quality-of-life even prefracture. To determine whether osteoporosis should be a greater concern in women Veterans versus non-Veterans, we compared fracture rates and bone mineral density (BMD) for Veterans and non-Veterans using Womens Health Initiative data. DESIGN AND METHODS In this cohort study, participants were women aged 50-79 years. Outcomes were hip, central body, and limb fractures occurring during up to 19 years of follow-up and hip, spine, and whole body BMD collected three times over a 6-year period in a participant subsample. Covariates comprised risk factors for fracture, including fall history and other components of the World Health Organization Fracture Risk Assessment Tool (FRAX). Cox Proportional Hazards models were used to examine fracture rates for Veterans compared with non-Veterans. RESULTS Of 161,808 women, 145,521 self-identified as Veteran (n = 3,719) or non-Veteran (n = 141,802). Baseline FRAX scores showed that Veterans had higher 10-year probabilities for any major fracture (13.3 vs 10.2; p < .01) and hip fracture (4.1 vs 2.2; p < .01) compared with non-Veterans. The age-adjusted rate of hip fracture per 1,000 person-years for Veterans was 3.3 versus 2.4 for non-Veterans (p < .01). After adjustment, the hazards ratio for hip fracture was 1.24 (95% confidence interval 1.03-1.49) for Veterans versus non-Veterans. Hazards ratios at other anatomic sites did not differ by Veteran status. Mean BMD at baseline and at Years 3 and 6 also did not differ by Veteran status at any site. IMPLICATIONS Women Veterans had an increased hip fracture rate not explained by differences in well-recognized fracture risk factors.

Multiple Sclerosis and Risk of Infection-Related Hospitalization and Death in US Veterans.

BACKGROUND This study estimated the risk of infection-related hospitalizations and death in patients with and without multiple sclerosis (MS). METHODS We identified adults with MS in the US Department of Veterans Affairs (VA) system between 1999 and 2010. Each veteran with MS was matched, on age and sex, with up to four veterans without MS. Multivariable Cox proportional hazards regression models were performed to assess the influence of MS on the development of serious and fatal infections. RESULTS The cohort included 7743 veterans with MS and 30,972 veterans without MS. Mean (SD) age was 53.8 (13.3) years, and 80.8% were male. The incidence per 1000 person-years of overall serious infections was 19.2 (95% confidence interval [CI], 17.6-20.8) for those with MS and 10.3 (95% CI, 9.8-10.9) for those without MS. Fatal infection incidence rates were 1.2 (95% CI, 0.8-1.7) for patients with MS and 0.5 (95% CI, 0.3-0.6) for patients without MS. Regression models showed that veterans with MS were at greater risk for overall serious (hazard ratio [HR] = 1.52, P < .01) and fatal (HR = 1.85, P = .03) infections and serious respiratory (HR = 1.31, P = .01), urinary tract (HR = 4.44, P < .01), and sepsis-related infections (HR = 2.56, P < .01). CONCLUSIONS This study provides evidence that VA patients with MS are more likely than those without MS to be hospitalized and die of infection.

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.

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.

Health Care Costs in a Cohort of HIV-Infected U.S. Veterans Receiving Regimens Containing Tenofovir Disoproxil Fumarate/Emtricitabine

BACKGROUND Tenofovir disoproxil fumarate (TDF), a key component in many human immunodeficiency virus (HIV) treatment regimens, is associated with increased renal and bone toxicities. The contributions of such toxicities to treatment costs, as well as the relative differences in treatment costs for various TDF/emtricitabine (FTC) regimens, remains unexplored. OBJECTIVE To estimate and compare mean overall and renal- and bone-specific costs, including total, inpatient, outpatient, and pharmacy costs in patients treated with TDF/FTC+efavirenz (EFV) compared with several non-EFV-containing TDF/FTC regimens. METHODS We conducted a national cohort study of treatment-naive HIV-infected U.S. veterans who initiated treatment from 2003 to 2015 with TDF/FTC in combination with EFV, elvitegravir/cobicistat, rilpivirine, or ritonavir-boosted protease inhibitors (atazanavir, darunavir, or lopinavir). Outcomes of interest were quarterly total, inpatient, outpatient, and pharmacy costs using data from the Veterans Health Administration (VHA) electronic medical record and Managerial Cost Accounting System (an activity-based accounting system that allocates VHA expenditures to patient encounters). We controlled for measured confounders using inverse probability of treatment (IPT) weights and assessed differences using standardized mean differences (SMDs). For comparisons where SMDs exceeded 0.1 after IPT weighting, we used the more conservative matching weights in sensitivity analyses. For hypothesis testing, we compared IPT-adjusted differences in quarterly costs between treatment groups using Mann-Whitney U-tests and generalized estimating equation (GEE) regression models. RESULTS Of 33,048 HIV-positive veterans, 7,222 met eligibility criteria, including 4,172 TDF/FTC + EFV recipients; mean (SD) age of the cohort was 50.0 (10.0) years; 96.7% were male; 60.1% were black; and 30.1% were white. Quarterly periods of exposure to EFV-containing regimens were 22,499 and of exposure to non-EFV-containing regimens were 11,633. After IPT weighting, absolute SMDs were < 0.1 except for a few covariates in the rilpivirine comparison. The per-patient adjusted mean total quarterly costs were

Clinical and Economic Outcomes of Ranolazine Versus Conventional Antianginals Users Among Veterans With Chronic Stable Angina Pectoris

7,145 for EFV versus

Rates of Early Treatment for US Veterans With Multiple Sclerosis

8,726 for non-EFV (P < 0.001; Mann-Whitney U-test) and the per-patient adjusted mean difference in total quarterly costs was

Analysis of osteoporosis treatment patterns with bisphosphonates and outcomes among postmenopausal veterans

1,419 lower for EFV versus all non-EFV combined (P < 0.001; GEE model). Corresponding values for outpatient costs (

Determining Multiple Sclerosis Phenotype from Electronic Medical Records

2,656 vs.