Cardiovascular events among patients with prostate cancer treated with abiraterone and enzalutamide.

BACKGROUND AND PURPOSE: There is growing concern about the adverse metabolic and cardiovascular effects of abiraterone acetate (AA) and enzalutamide (ENZ), two standard hormonal therapies for prostate cancer. We analysed the risk of cardiovascular adverse events among patients treated with AA and ENZ. PATIENTS AND METHODS: We used Kythera Medicare data from January 2019 to June 2023 to identify patients with at least one pharmacy claim for AA or ENZ. The index date was the first prescription claim date. Patients were required to have 1 year of data pre- and post-index date. New users excluded those with prior AA or ENZ claims and pre-existing cardiovascular comorbidities. Demographic and clinical variables, including age, socioeconomic status (SES), comorbidity score, prostate-specific comorbidities, and healthcare costs, were analysed . Propensity score matching was employed for risk adjustment. RESULTS: Of the 8,929 and 8,624 patients in the AA and ENZ cohorts, respectively, 7,647 were matched after adjusting for age, sociodemographic, and clinical factors. Between the matched cohorts (15.54% vs. 14.83%, p < 0.05), there were no statistically significant differences in any cardiovascular event after adjusting for these factors. The most common cardiovascular event in both cohorts was heart failure (5.20% vs. 4.49%), followed by atrial fibrillation (4.42% vs. 3.60%) and hypotension (2.93% vs. 2.48%). INTERPRETATION: This study provides real-world evidence of the cardiovascular risk of AA and ENZ that may not appear in clinical trial settings. Adjusting for age, baseline comorbidities, and SES, the likelihood of a cardiovascular event did not differ between treatment groups.

Prevalence of mastocytosis and Hymenoptera venom allergy in the United States.

BACKGROUND: Mastocytosis is a risk factor for Hymenoptera venom anaphylaxis (HVA). Current guidelines recommend measuring tryptase in patients with HVA and that those with mastocytosis pursue lifelong venom immunotherapy (VIT). Available data on HVA and mastocytosis largely derive from European single-center studies, and the prevalence of HVA with and without mastocytosis in the United States is unknown. OBJECTIVE: We sought to determine the prevalence of HVA and mastocytosis in the United States using an insurance claims database and evaluate the impact of mastocytosis on VIT in patients with HVA in a US cohort. METHODS: The IBM Watson Database, consisting of insurance claims from approximately 27 million US patients in 2018, was queried to identify patients with HVA and/or mastocytosis. Furthermore, a retrospective study of 161 patients undergoing VIT between 2015 and 2018 at the University of Michigan was conducted. RESULTS: In the IBM Watson Database, the prevalence of HVA was 167 per 100,000 (0.167%) and the prevalence of mastocytosis 10 per 100,000 (0.010%) overall and 97 per 100,000 (0.097%) among those with HVA. Mastocytosis showed a 9.7-fold increase among patients with HVA versus the general population. In the U-M cohort, 2.6% of patients with VIT had mastocytosis. Tryptase level did not correlate with venom reaction severity but was higher in patients with systemic VIT reactions. CONCLUSIONS: We observed a lower US HVA prevalence than previously reported. Mastocytosis was more common in US patients with HVA, though at lower rates than previously reported. In patients with VIT there was no correlation between tryptase level and reaction severity.

Real-world adherence and persistence for newly-prescribed HIV treatment: single versus multiple tablet regimen comparison among US medicaid beneficiaries.

BACKGROUND: Once-daily, single-tablet regimens (STRs) have been associated with improved patient outcomes compared to multi-tablet regimens (MTRs). This study evaluated real world adherence and persistence of HIV antiretroviral therapy (ART), comparing STRs and MTRs. METHODS: Adult Medicaid beneficiaries (aged ≥ 18 years) initiating ART with ≥ 2 ART claims during the identification period (January 1, 2015-December 31, 2016) and continuous health plan enrollment for a 12-month baseline period were included. For STRs, the first ART claim date was defined as the index date; for MTRs, the prescription fill claim date for the last drug in the regimen was defined as the index date, and prescription fills were required to occur within a 5-day window. Adherence was assessed in 30-day intervals over a 6-month period, with adherence defined as having less than a 5-day gap between fills. Persistence was evaluated as median number of days on therapy and percent persistence at 12 months. Cox Proportional Hazard models were used to evaluate risk of discontinuation, controlling for baseline and clinical characteristics. RESULTS: A total of 1,744 (STR = 1290; MTR = 454) and 2409 (STR = 1782; MTR = 627) patients newly prescribed ART had available data concerning adherence and persistence, respectively. Average age ranged 40-42 years. The patient population was predominantly male. Adherence assessments showed 22.7% of STR initiators were adherent to their index regimens over a 6-month period compared to 11.7% of MTR initiators. Unadjusted persistence analysis showed 36.3% of STR initiators discontinued first-line therapy compared to 48.8% for MTR initiators over the 2-year study period. Controlling for baseline demographic and clinical characteristics, MTR initiators had a higher risk of treatment discontinuation (hazard ratio [HR] = 1.6, p < 0.0001). Among STRs, compared to the referent elvitegravir(EVG)/cobicistat(COBI)/emtricitabine(FTC)/tenofovir alafenamide(TAF), risk of discontinuation was higher for efavirenz(EFV)/FTC/tenofovir disoproxil fumarate(TDF) (HR = 3.6, p < 0.0001), EVG/COBI/FTC/TDF (HR = 2.8, p < 0.0001), and abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) (HR = 1.8, p = 0.004). Among backbones, FTC/TAF was associated with lower risk of discontinuation than FTC/TDF (HR = 4.4, p < 0.0001) and ABC/3TC (HR = 2.2, p < 0.0001). CONCLUSIONS: Among patients newly prescribed ART, STR initiators were significantly less likely to discontinue therapy and had greater adherence and persistence compared to MTR initiators. Regimens containing FTC/TAF as a backbone had higher persistence than those consisting of other backbones.

Hematocrit levels and thrombotic events in patients with polycythemia vera: an analysis of Veterans Health Administration data.

Patients with polycythemia vera (PV) have a high incidence of thrombotic events (TEs), contributing to a greater mortality risk than the general population. The relationship between hematocrit (HCT) levels and TE occurrence among patients with PV from the Veterans Health Administration (VHA) was evaluated to replicate findings of the CYTO-PV trial with a real-world patient population. This retrospective study used VHA medical record and claims data from the first claim with a PV diagnosis (index) until death, disenrollment, or end of study, collected between October 1, 2005, and September 30, 2012. Patients were aged ≥ 18 years at index, had ≥ 2 claims for PV (ICD-9-CM code, 238.4) ≥ 30 days apart during the identification period, continuous health plan enrollment from 12 months pre-index until end of study, and ≥ 3 HCT measurements per year during follow-up. This analysis focused on patients with no pre-index TE, and with all HCT values either < 45% or ≥ 45% during the follow-up period. The difference in TE risk between HCT groups was assessed using unadjusted Cox regression models based on time to first TE. Patients (N = 213) were mean (SD) age 68.9 (11.5) years, 98.6% male, and 61.5% white. TE rates for patients with HCT values < 45% versus ≥ 45% were 40.3% and 54.2%, respectively. Among patients with ≥ 1 HCT before TE, TE risk hazard ratio was 1.61 (95% CI, 1.03-2.51; P = 0.036). This analysis of the VHA population further supports effective monitoring and control of HCT levels < 45% to reduce TE risk in patients with PV.

Cardiovascular outcomes among elderly patients with heart failure and coronary artery disease and without atrial fibrillation: a retrospective cohort study.

BACKGROUND: Coronary artery disease accelerates heart failure progression, leading to poor prognosis and a substantial increase in morbidity and mortality. This study was aimed to assess the impact of coronary artery disease on all-cause mortality, myocardial infarction (MI), and ischemic stroke (IS) among hospitalized newly-diagnosed heart failure (HF) patients with left ventricular systolic dysfunction (LVSD). METHODS: This retrospective cohort study included Medicare patients (aged ≥65 years) with ≥1 inpatient heart failure claim (index date = discharge date) during 01JAN2007-31DEC2013. Patients were required to have continuous enrollment for ≥1-year pre-index date (baseline: 1-year pre-index period) without a prior heart failure claim (in the 1 year pre-index prior to the index hospital admission); follow-up ran from the index date to death, disenrollment from the health plan, or the end of the study period, whichever occurred first. HF with LVSD patients, identified with diagnosis codes of systolic dysfunction (excluding baseline atrial fibrillation), were stratified based on prevalent coronary artery disease at baseline into coronary artery disease and non-coronary artery disease cohorts. Main outcomes were occurrence of major adverse cardiovascular events including all-cause mortality, myocardial infarction, and ischemic stroke. Propensity score matching (PSM) was used to balance patient characteristics. Kaplan-Meier curves of ACM and cumulative incidence distribution of MI/IS were presented. RESULTS: Of 22,230 HF with LVSD patients, 15,827 (71.2%) had coronary artery disease and were overall more likely to be younger (79.8 vs 80.9 years), male (49.6% vs. 35.6%), white (86.2% vs 81.4%), with more prevalent comorbidities including hypertension (80.7% vs 74.3%), hyperlipidemia (67.7% vs 46.7%), and diabetes (46.3% vs 35.8%) (all p < 0.0001). After propensity score matching, cohorts included 5792 patients each. The coronary artery disease cohort had significantly higher cumulative incidence of myocardial infarction and ischemic stroke at the end of 7-year follow-up vs non-coronary artery disease (myocardial infarction = 50.0% vs 18.0%; ischemic stroke = 23.3% vs 18.7%; all p < 0.0001). Follow-up all-cause mortality rates were similar between the two cohorts. CONCLUSIONS: HF with LVSD patients with coronary artery disease had significantly higher incidence of ischemic stroke and myocardial infarction, but similar all-cause mortality compared to those without coronary artery disease.

The value of sPESI for risk stratification in patients with pulmonary embolism.

INTRODUCTION: Various risk stratification methods exist for patients with pulmonary embolism (PE). We used the simplified Pulmonary Embolism Severity Index (sPESI) as a risk-stratification method to understand the Veterans Health Administration (VHA) PE population. MATERIALS AND METHODS: Adult patients with ≥ 1 inpatient PE diagnosis (index date = discharge date) from October 2011-June 2015 as well as continuous enrollment for ≥ 12 months pre- and 3 months post-index date were included. We defined a sPESI score of 0 as low-risk (LRPE) and all others as high-risk (HRPE). Hospital-acquired complications (HACs) during the index hospitalization, 90-day follow-up PE-related outcomes, and health care utilization and costs were compared between HRPE and LRPE patients. RESULTS: Of 6746 PE patients, 95.4% were men, 67.7% were white, and 22.0% were African American; LRPE occurred in 28.4% and HRPE in 71.6%. Relative to HRPE patients, LRPE patients had lower Charlson Comorbidity Index scores (1.0 vs. 3.4, p < 0.0001) and other baseline comorbidities, fewer HACs (11.4% vs. 20.0%, p < 0.0001), less bacterial pneumonia (10.6% vs. 22.3%, p < 0.0001), and shorter average inpatient lengths of stay (8.8 vs. 11.2 days, p < 0.0001) during the index hospitalization. During follow-up, LRPE patients had fewer PE-related outcomes of recurrent venous thromboembolism (4.4% vs. 6.0%, p = 0.0077), major bleeding (1.2% vs. 1.9%, p = 0.0382), and death (3.7% vs. 16.2%, p < 0.0001). LRPE patients had fewer inpatient but higher outpatient visits per patient, and lower total health care costs ($12,021 vs. $16,911, p < 0.0001) than HRPE patients. CONCLUSIONS: Using the sPESI score identifies a PE cohort with a lower clinical and economic burden.

Effectiveness and Safety of Oral Anticoagulants Among Nonvalvular Atrial Fibrillation Patients.

Background and Purpose- This ARISTOPHANES study (Anticoagulants for Reduction in Stroke: Observational Pooled Analysis on Health Outcomes and Experience of Patients) used multiple data sources to compare stroke/systemic embolism (SE) and major bleeding (MB) among a large number of nonvalvular atrial fibrillation patients on non-vitamin K antagonist oral anticoagulants (NOACs) or warfarin. Methods- A retrospective observational study of nonvalvular atrial fibrillation patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from January 1, 2013, to September 30, 2015, was conducted pooling Centers for Medicare and Medicaid Services Medicare data and 4 US commercial claims databases. After 1:1 NOAC-warfarin and NOAC-NOAC propensity score matching in each database, the resulting patient records were pooled. Cox models were used to evaluate the risk of stroke/SE and MB across matched cohorts. Results- A total of 285 292 patients were included in the 6 matched cohorts: 57 929 apixaban-warfarin, 26 838 dabigatran-warfarin, 83 007 rivaroxaban-warfarin, 27 096 apixaban-dabigatran, 62 619 apixaban-rivaroxaban, and 27 538 dabigatran-rivaroxaban patient pairs. Apixaban (hazard ratio [HR], 0.61; 95% CI, 0.54-0.69), dabigatran (HR, 0.80; 95% CI, 0.68-0.94), and rivaroxaban (HR, 0.75; 95% CI, 0.69-0.82) were associated with lower rates of stroke/SE compared with warfarin. Apixaban (HR, 0.58; 95% CI, 0.54-0.62) and dabigatran (HR, 0.73; 95% CI, 0.66-0.81) had lower rates of MB, and rivaroxaban (HR, 1.07; 95% CI, 1.02-1.13) had a higher rate of MB compared with warfarin. Differences exist in rates of stroke/SE and MB across NOACs. Conclusions- In this largest observational study to date on NOACs and warfarin, the NOACs had lower rates of stroke/SE and variable comparative rates of MB versus warfarin. The findings from this study may help inform the discussion on benefit and risk in the shared decision-making process for stroke prevention between healthcare providers and nonvalvular atrial fibrillation patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT03087487.

Cytoreductive treatment patterns among US veterans with polycythemia vera.

BACKGROUND: Polycythemia vera (PV) is a myeloproliferative neoplasm associated with increased thrombotic and cardiovascular risk, which are key contributors to patient morbidity and mortality. The Veterans Health Administration (VHA) is the largest integrative health network in the United States. Available data concerning patients with PV in this population are limited. METHODS: This retrospective observational study evaluated the characteristics, management, and outcomes of patients with PV in the VHA Medical SAS® Dataset (October 1, 2005, to September 30, 2012). Inclusion criteria were ≥ 2 claims for PV (ie, PV diagnostic code was recorded) ≥30 days apart during the identification period, age ≥ 18 years, and continuous health plan enrollment from ≥12 months before the index date until the end of follow-up. All data were analyzed using descriptive statistics. RESULTS: The analysis included 7718 patients (median age, 64 years; male, 98%; white, 64%). The most common comorbidities before the index date were hypertension (72%), dyslipidemia (54%), and diabetes (24%); 33% had a history of smoking. During the follow-up period (median, 4.8 years), most patients did not receive treatment with cytoreductive therapy, including phlebotomy (53%), or antiplatelet agents, such as aspirin (57%). The thrombotic and cardiovascular event rates per 1000 patient-years were 60.5 and 83.8, respectively. Among patients who received cytoreductive treatment, the thrombotic event rate was 48.9 per 1000 patient-years. The overall mortality rate was 51.2 per 1000 patient-years. CONCLUSION: The notable rates of thrombotic and cardiovascular events observed in this analysis, even among patients receiving cytoreductive treatment, highlight the important unmet clinical needs of patients with PV in the VHA.

Taxane chemotherapy vs antiandrogen agents as first-line therapy for metastatic castration-resistant prostate cancer.

OBJECTIVES: To assess treatment patterns and outcomes of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line chemotherapy or antiandrogen therapy. PATIENTS AND METHODS: Patients initiating first-line antiandrogen therapy (abiraterone, enzalutamide) or chemotherapy (taxane) between October 2012 and September 2014 were retrospectively identified in the US Veterans Health Administration database. The impact of antiandrogen therapy vs chemotherapy on overall survival (OS) and time to discontinuation was assessed using Cox proportional hazard models, adjusting for prior androgen deprivation therapy (ADT) duration and available prognostic factors. RESULTS: Overall, 1445 patients were evaluable, of whom 1108 received antiandrogen therapy and 337 received chemotherapy (docetaxel). On multivariable analysis and propensity score analysis, the OS times for antiandrogen therapy vs chemotherapy were not significantly different (hazard ratio [HR] 1.041, 95% confidence interval (CI) 0.853-1.270, P = 0.694, and HR 1.047, 95% CI 0.861-1.273, P = 0.644, respectively). Time to discontinuation was shorter for chemotherapy vs antiandrogen therapy (HR 2.339, 95% CI 1.969-2.779; P < 0.001). Prior ADT duration above the median was associated with longer OS (HR 0.566, 95% CI 0.464-0.690; P < 0.001) and time to discontinuation (HR 0.831, 95% CI 0.699-0.988; P = 0.036) in the antiandrogen therapy cohort and not the chemotherapy cohort, while prior ADT duration below the median was associated with higher prostate specific antigen (PSA) response rate in the chemotherapy vs antiandrogen therapy cohort (61.5% vs 51.1%; P = 0.024). The treatment-free interval after discontinuation was longer after first-line chemotherapy vs antiandrogen therapy (mean 53 vs 39 days; P = 0.030). CONCLUSION: After adjusting for key prognostic factors in this large mCRPC dataset, the OS was similar for first-line chemotherapy vs antiandrogen therapy despite shorter time to discontinuation with chemotherapy and longer treatment-free interval after first-line chemotherapy. These hypothesis-generating data also suggest that duration of prior ADT may assist in the selection of patients for chemotherapy vs antiandrogen therapy.

Effect of Renal Function on Dosing of Non-Vitamin K Antagonist Direct Oral Anticoagulants Among Patients With Nonvalvular Atrial Fibrillation.

BACKGROUND: Non-vitamin K antagonist direct oral anticoagulants (DOACs) are fixed-dose regimens indicated for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients. Dose adjustment is necessary among patients with renal insufficiency to optimize efficacy and safety. OBJECTIVE: To assess DOAC dosing appropriateness and its effect on clinical outcomes in NVAF patients. METHODS: Adult NVAF patients with ≥1 DOAC pharmacy claim (January 1, 2013, to December 31, 2014), continuous enrollment for ≥12 months post-index DOAC claim, and documented creatinine clearance within 3 months preindex date in the Optum/Humedica SmartFile database were eligible. DOAC dosage was classified as inappropriate or appropriate by level of renal function, age, and body weight per US prescription information. Cox proportional models were used to assess the risks of bleeding and stroke associated with inappropriate DOAC dosage. RESULTS: Of the 388 eligible patients, 69 (17.8%) were inappropriately dosed, and rivaroxaban had the highest inappropriate dosing rate. Most inappropriately dosed patients were underdosed. Inappropriately dosed patients were more likely to be older, female, and have a body weight of ≤60 kg; they also had higher mean CHA2DS2-VASc and Charlson comorbidity index scores (all P < 0.05). Overtreated patients had a higher risk of bleeding (hazard ratio [HR] = 5.4; P = 0.006) than undertreated patients (HR = 3.1; P = 0.025) relative to appropriately dosed patients. However, no significant difference in stroke risk was observed, most likely because very few stroke events were observed in the study. CONCLUSIONS: Inappropriate dosing occurred among patients with normal and insufficient renal function. The consideration of clinical factors beyond renal function is necessary to reduce bleeding risk associated with DOAC therapy.

Visceral fat area, not body mass index, predicts postoperative 30-day morbidity in patients undergoing colon resection for cancer.

PURPOSE: Colectomy for cancer in obese patients is technically challenging and may be associated with worse outcomes. Whether visceral obesity, as measured on computed tomography, is a better predictor of complication than body mass index (BMI) or determines long-term oncologic outcomes has not been well characterized. This study examines the association between derived anthropometrics and postoperative complication and long-term oncologic outcomes. METHODS: Retrospective review of patients undergoing elective colectomy for cancer at a single tertiary-care center from 2010 to 2016. Adipose tissue distribution measurements, including visceral fat area (VFA), were determined from preoperative imaging. The primary outcome was 30-day postoperative complication; secondary outcomes included overall and disease-free survival. Multivariable logistic regression was performed to determine association between obesity metrics and outcome. RESULTS: Two hundred and sixty-four patients underwent 266 primary resections of colon cancer. Twenty-eight patients (10.5%) developed major morbidity (Clavien-Dindo grade ≥ III). VFA but not BMI was significantly associated with morbidity in multivariate analysis (p = 0.004, odds ratio 1.99, 95% confidence interval 1.25-3.19). No other imaging-derived anthropometric was associated with increased morbidity. In receiver operating characteristic analysis, VFA was predictive of major morbidity (area under curve 0.660). A cutoff value of VFA ≥ 191 cm2 was associated with 50% sensitivity and 76% specificity for predicting major morbidity. Patients with VFA ≥ 191cm2 had 19.4% risk of morbidity, whereas those with < 191 cm2 had 7.2% risk (relative risk ratio 2.69, unadjusted p = 0.004). Neither VFA nor BMI was associated with overall or disease-free survival. CONCLUSION: VFA but not BMI predicts morbidity following elective surgery for colon cancer.

The Use of Decomposition Methods in Real-World Treatment Benefits Evaluation for Patients with Type 2 Diabetes Initiating Different Injectable Therapies: Findings from the INITIATOR Study.

BACKGROUND: Determining characteristics of patients likely to benefit from a particular treatment could help physicians set personalized targets. OBJECTIVES: To use decomposition methodology on real-world data to identify the relative contributions of treatment effects and patients' baseline characteristics. METHODS: Decomposition analyses were performed on data from the Initiation of New Injectable Treatment Introduced after Antidiabetic Therapy with Oral-only Regimens (INITIATOR) study, a real-world study of patients with type 2 diabetes started on insulin glargine (GLA) or liraglutide (LIRA). These analyses investigated relative contributions of differences in baseline characteristics and treatment effects to observed differences in 1-year outcomes for reduction in glycated hemoglobin A1c (HbA1c) and treatment persistence. RESULTS: The greater HbA1c reduction seen with GLA compared with LIRA (-1.39% vs. -0.74%) was primarily due to differences in baseline characteristics (HbA1c and endocrinologist as prescribing physician; P < 0.050). Patients with baseline HbA1c of 9.0% or more or evidence of diagnosis codes related to mental illness achieved greater HbA1c reductions with GLA, whereas patients with baseline polypharmacy (6-10 classes) or hypogylcemia achieved greater reductions with LIRA. Decomposition analyses also showed that the higher persistence seen with GLA (65% vs. 49%) was mainly caused by differences in treatment effects (P < 0.001). Patients 65 years and older, those with HbA1c of 9.0% or more, those taking three oral antidiabetes drugs, and those with polypharmacy of more than 10 classes had higher persistence with GLA; patients 18 to 39 years and those with HbA1c of 7.0% to less than 8.0% had higher persistence with LIRA. CONCLUSIONS: Although decomposition does not demonstrate causal relationships, this method could be useful for examining the source of differences in outcomes between treatments in a real-world setting and could help physicians identify patients likely to respond to a particular treatment.

Warfarin Discontinuation in Patients With Unprovoked Venous Thromboembolism: A Large US Insurance Database Analysis.

This study examined warfarin therapy discontinuation and its risk factors among patients with unprovoked venous thromboembolism (VTE) in the US clinical practice setting. Adult patients with unprovoked VTE were identified from the MarketScan claims database from January 1, 2006 to December 31, 2012. The index date was defined as the date of first VTE diagnosis. Patients were required to have no VTE diagnosis in the 6 months before index date and continuous health plan enrollment for 6 months before and 12 months after the index date. Warfarin discontinuation rates and adjusted hazard ratios (HRs) were reported. Of 21,163 eligible patients, 15,463 were diagnosed with deep vein thrombosis (DVT) only (73.1%), 5027 with pulmonary embolism (PE) only (23.7%), and 673 with DVT and PE (3.2%). The average duration of warfarin therapy was 5.2 months (SD = 3.0). During 1-year follow-up, 21.4% patients discontinued therapy within 3 months, 42.8% within 6 months, and 70.1% within 12 months. PE versus DVT [HR = 0.77, 95% confidence interval (CI) = 0.74-0.80], comorbid atrial fibrillation (HR = 0.73, 95% CI = 0.66-0.81), thrombophilia (HR = 0.62, 95% CI = 0.54-0.71), and age >40 years (41-65 years: HR = 0.86, 95% CI = 0.81-0.91; >65 years: HR = 0.82, 95% CI = 0.77-0.87) were significantly associated with reduced risk of warfarin discontinuation. Alcohol abuse/dependence (HR = 1.36, 95% CI = 1.20-1.55), cancer history (HR = 1.13, 95% CI = 1.07-1.19), bleeding (HR = 1.07, 95% CI = 1.01-1.15), and catheter ablation (HR = 1.10, 95% CI = 1.00-1.20) in the 6 months before index date were significantly associated with increased risk for warfarin discontinuation. In conclusion, nearly 1 of 4 patients with unprovoked VTE discontinued warfarin within 3 months. Three of 4 patients discontinued therapy within 1 year. Younger age and multiple clinical factors are associated with warfarin therapy discontinuation.

Clinical and economic burden associated with cardiovascular events among patients with hyperlipidemia: a retrospective cohort study.

BACKGROUND: Annual direct costs for cardiovascular (CV) diseases in the United States are approximately $195.6 billion, with many high-risk patients remaining at risk for major cardiovascular events (CVE). This study evaluated the direct clinical and economic burden associated with new CVE up to 3 years post-event among patients with hyperlipidemia. METHODS: Hyperlipidemic patients with a primary inpatient claim for new CVE (myocardial infarction, unstable angina, ischemic stroke, transient ischemic attack, coronary artery bypass graft, percutaneous coronary intervention and heart failure) were identified using IMS LifeLink PharMetrics Plus data from January 1, 2006 through June 30, 2012. Patients were stratified by CV risk into history of CVE, modified coronary heart disease risk equivalent, moderate- and low-risk cohorts. Of the eligible patients, propensity score matched 243,640 patients with or without new CVE were included to compare healthcare resource utilization and direct costs ranging from the acute (1-month) phase through 3 years post-CVE date (follow-up period). RESULTS: Myocardial infarction was the most common CVE in all the risk cohorts. During the acute phase, among patients with new CVE, the average incremental inpatient length of stay and incremental costs ranged from 4.4-6.2 days and $25,666-$30,321, respectively. Acute-phase incremental costs accounted for 61-75% of first-year costs, but incremental costs also remained high during years 2 and 3 post-CVE. CONCLUSIONS: Among hyperlipidemic patients with new CVE, healthcare utilization and costs incurred were significantly higher than for those without CVE during the acute phase, and remained higher up to 3 years post-event, across all risk cohorts.

Burden of Clostridium difficile-associated disease among patients residing in nursing homes: a population-based cohort study.

BACKGROUND: Clostridium difficile (C. difficile) infection (CDI) is the leading cause of nosocomial diarrhea in the United States. This study aimed to examine the incidence of CDI and evaluate mortality and economic burden of CDI in an elderly population who reside in nursing homes (NHs). METHODS: This was a population-based retrospective cohort study focusing on US NHs by linking Medicare 5% sample, Medicaid, Minimum Data Set (MDS) (2008-10). NH residents aged ≥65 years with continuous enrollment in Medicare and/or Medicaid Fee-for-Service plan for ≥12 months and ≥2 quarterly MDS assessments were eligible for the study. The incidence rate was calculated as the number of CDI episodes by 100,000 person-years. A 1:4 propensity score matched sample of cohorts with and without CDI was generated to assess mortality and health care costs following the first CDI. RESULTS: Among 32,807 NH residents, 941 residents had ≥1 episode of CDI in 2009, with an incidence of 3359.9 per 100,000 person-years. About 30% CDI episodes occurred in the hospital setting. NH residents with CDI (vs without CDI) were more likely to have congestive heart failure, renal disease, cerebrovascular disease, hospitalizations, and outpatient antibiotic use. During the follow-up period, the 30-day (14.7% vs 4.3%, P < 0.001), 60-day (22.7% vs 7.5%, P < 0.001), 6-month (36.3% vs 18.3%, P < 0.001), and 1-year mortality rates (48.2% vs 31.1%, P < 0.001) were significantly higher among the CDI residents vs non-CDI residents. Total health care costs within 2 months following the first CDI episode were also significantly higher for CDI residents ($28,621 vs $13,644, P < 0.001). CONCLUSIONS: CDI presents a serious public health issue in NHs. Mortality, health care utilization, and associated costs were significant following incident CDI episodes.

HIV economic burden of illness in the Veterans Health Administration population.

The objective was to assess the human immunodeficiency virus (HIV) economic burden of illness in the Veterans Health Administration (VHA) population. Adults (aged 18-64 years) with a HIV diagnosis (International Classification of Diseases 9th Revision, Clinical Modification [ICD-9-CM] code 042.x, V08) from 1 June 2007 to 31 May 2012 were selected from VHA Medical SAS(®) data-sets. Continuous VHA insurance coverage 12-month pre- and postindex date, with no antiretroviral therapy (ART) prescriptions within 180 days pre-index date, was required for treatment-naive (TN) HIV-infected patients. One baseline CD4 count or HIV viral load measured within three months after HIV diagnosis or one ART anchor drug claim postindex date was required for group comparison. All-cause health-care costs and utilizations were evaluated and stratified by CD4 cell count, viral load, nonnucleoside reverse transcriptase inhibitor (NNRTI) anchor drugs (efavirenz/non-efavirenz), and ART (NNRTI/PI/INSTI/CCR-5 Antagonist-based) regimen cohorts. The overall economic burden was compared between HIV-infected vs. non-HIV-infected patients. CD4 count, viral load, and treatment patterns and the associated costs were compared among TN patients. A 1:1 propensity score matching (PSM) was used to adjust for baseline differences. A total of 25,648 HIV-infected patients were identified (mean age 51; 96.4% male; 49.7% non-Hispanic black) of which 11,371 were TN. HIV-infected patients incurred higher PSM-adjusted total costs than non-HIV-infected patients ($25,232 vs. $10,206, p < 0.0001). Total costs for TN with CD4 cell counts ≤50 cells/mm(3) were higher than all other CD4 cell strata (p < 0.001). Total costs for TN with viral loads >100,000 copies/mL were higher than all other viral load categories (p < 0.001). Efavirenz-treated patients incurred higher ART-related ($8663 vs. $2846, p = 0.0266), but lower non-ART-related ($2339 vs. $6628, p = 0.0042) pharmacy costs than non-efavirenz patients. NNRTI-based cohort incurred lower total costs than protease inhibitor-based ($32,829 vs. $39,073, p = 0.0005) but no significant differences compared to integrase strand transfer inhibitor cohorts. This study offers new health-care costs and resource utilization estimates associated with the burden of HIV in the VHA population.

The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: The study aims to assess the relative efficacy of granulocyte colony-stimulating factor (G-CSF) products administered as primary prophylaxis (PP) to patients with cancer receiving myelosuppressive chemotherapy. METHODS: A systematic literature review identified publications (January 1990 to September 2013) of randomized controlled trials evaluating PP with filgrastim, pegfilgrastim, lenograstim, or lipegfilgrastim in adults receiving myelosuppressive chemotherapy for solid tumors or non-Hodgkin lymphoma. Direct, indirect, and mixed-treatment comparison (MTC) were used to estimate the odds ratio and 95 % credible interval of febrile neutropenia (FN) during cycle 1 and all cycles of chemotherapy combined without adjusting for differences in relative dose intensity (RDI) between study treatment arms. RESULTS: Twenty-seven publications representing 30 randomized controlled trials were included. Using MTC over all chemotherapy cycles, PP with filgrastim, pegfilgrastim, lenograstim, and lipegfilgrastim versus no G-CSF PP or placebo were associated with statistically significantly reduced FN risk. FN risk was also significantly reduced with pegfilgrastim PP versus filgrastim PP. Over all chemotherapy cycles, there was a numerical but statistically nonsignificant increase in the FN risk for lipegfilgrastim PP versus pegfilgrastim PP. Using MTC in cycle 1, PP with filgrastim, pegfilgrastim, and lipegfilgrastim versus no G-CSF PP or placebo were associated with statistically significantly reduced FN risk. CONCLUSIONS: In this meta-analysis, using MTC without adjustment for RDI, PP with all G-CSFs evaluated reduced the FN risk in patients receiving myelosuppressive chemotherapy. Future studies are needed to assess the influence of RDI on FN outcomes and to eliminate potential bias between G-CSF arms receiving more intensive chemotherapy than control arms.

Development of a Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose in Veterans' Health Administration Patients.

OBJECTIVE: Develop a risk index to estimate the likelihood of life-threatening respiratory depression or overdose among medical users of prescription opioids. SUBJECTS, DESIGN, AND METHODS: A case-control analysis of administrative health care data from the Veterans' Health Administration identified 1,877,841 patients with a pharmacy record for an opioid prescription between October 1, 2010 and September 30, 2012. Overdose or serious opioid-induced respiratory depression (OSORD) occurred in 817. Ten controls were selected per case (n = 8,170). Items for an OSORD risk index (RIOSORD) were selected through logistic regression modeling, with point values assigned to each predictor. Modeling of risk index scores produced predicted probabilities of OSORD; risk classes were defined by the predicted probability distribution. RESULTS: Fifteen variables most highly associated with OSORD were retained as items, including mental health disorders and pharmacotherapy; impaired drug metabolism or excretion; pulmonary disorders; specific opioid characteristics; and recent hospital visits. The average predicted probability of experiencing OSORD ranged from 3% in the lowest risk decile to 94% in the highest, with excellent agreement between predicted and observed incidence across risk classes. The model's C-statistic was 0.88 and Hosmer-Lemeshow goodness-of-fit statistic 10.8 (P > 0.05). CONCLUSION: RIOSORD performed well in identifying medical users of prescription opioids within the Veterans' Health Administration at elevated risk of overdose or life-threatening respiratory depression, those most likely to benefit from preventive interventions. This novel, clinically practical, risk index is intended to provide clinical decision support for safer pain management. It should be assessed, and refined as necessary, in a more generalizable population, and prospectively evaluated.

Adding Rapid-Acting Insulin or GLP-1 Receptor Agonist to Basal Insulin: Outcomes in a Community Setting.

OBJECTIVE: To evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist. METHODS: Data were extracted retrospectively from a U. S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up. RESULTS: Overall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P<.0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P<.0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P<.0001) compared with the basal + RAI cohort. CONCLUSIONS: Add-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin.

Hepatic decompensation in patients with HIV/Hepatitis B Virus (HBV)/Hepatitis C Virus (HCV) triple infection versus HIV/HCV coinfection and the effect of anti-HBV nucleos(t)ide therapy.

The incidence rate of hepatic decompensation was higher in patients with human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) triple infection than in those with HIV/HCV coinfection (24.1 vs 10.8 events per 1000 person-years; hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.12-3.18). Compared with HIV/HCV-infected patients, the rate of decompensation was increased among HIV/HBV/HCV-infected patients receiving no anti-HBV therapy (HR, 2.48; 95% CI, 1.37-4.49) but not among those who did receive such therapy (HR, 1.09; 95% CI, .40-2.97).