Hugh Kawabata

Coronary heart disease in HIV-infected individuals.

It is currently unknown whether there is an increased risk of coronary heart disease (CHD) in patients with HIV infection. In addition, the contribution of antiretroviral therapy (ART) to CHD risk has not been quantified. We reviewed administrative claims data for HIV-infected and -uninfected individuals from the California Medicaid population and compared the incidence of and relative risk (RR) for CHD using log-linear regression analyses between groups. The association between exposure to ART and CHD incidence was also assessed. Of 3,083,209 individuals analyzed, 28,513 were HIV-infected. The incidence of CHD among young men (up to age 34) and women (up to age 44) with HIV infection was significantly higher than that among non-HIV-infected individuals. The covariate-adjusted RR for the development of CHD in individuals receiving ART compared with those not receiving ART was 2.06 (P < 0.001) in HIV-infected individuals aged 18-33 years. There were no statistically significant associations between ART exposure and CHD in other age groups. CHD incidence appears accelerated among young HIV-infected individuals. Strategies to reduce CHD risk should be incorporated into HIV primary care.

Major bleeding risk among non-valvular atrial fibrillation patients initiated on apixaban, dabigatran, rivaroxaban or warfarin: a "real-world" observational study in the United States

Limited data are available about the real‐world safety of non‐vitamin K antagonist oral anticoagulants (NOACs).

Increased use of lipid-lowering therapy in patients receiving human immunodeficiency virus protease inhibitors☆

Although human immunodeficiency virus (HIV) protease inhibitors (PIs) improve survival in patients with HIV infection, many patients receiving PIs develop hyperlipidemia, which may increase risk of future coronary events. The purpose of this study was to estimate the changing prevalence of lipid-lowering therapy (LLT) in patients with HIV and to evaluate its association with the use of HIV PIs. This was a cross-sectional study of adults with HIV infection who were registered in the Medicaid of California (MEDI-CAL) administrative claims database. Frequencies of HIV-related and dyslipidemia diagnoses were determined from International Classification of Diseases-9th Edition codes. Use of lipid-lowering and antiretroviral medications was determined by National Drug Codes. Multivariate statistical techniques were used to evaluate trends in use of PIs and lipid-lowering medications from January 1996 to June 2002. The number of HIV-infected patients in MEDI-CAL ranged from 15,764 in 1996 to 13,349 in 2000. The prevalence of LLT use among HIV-infected patients on PIs increased by sixfold (1.7% to 10.6%, p <0.05), and in 2000, exceeded use in the overall MEDI-CAL population (p = 0.09). The increasing rate of LLT in patients taking PIs was greater than in HIV-infected patients not on PIs and in MEDI-CAL (p = 0.002). In multivariate models, increasing age (odds ratio 2.30) and use of PIs (odds ratio 2.08) predicted use of LLT (p <0.001). Thus, in patients taking HIV PIs, use of LLT increased more than sixfold, at a faster rate than in the general population. It has not been proved that use of LLT in HIV-infected patients taking PIs improves survival.

Selected adverse events in cancer patients treated with vascular endothelial growth factor inhibitors

INTRODUCTION To evaluate the safety profile of new drugs, it is important to quantify the rates of adverse events (AE). There has been little to no research on the safety of vascular endothelial growth factor (VEGF) inhibitors in population-based settings. The purpose of this study was to further the understanding of the incidence of AEs in a population-based representative cancer population receiving VEGF inhibitors where there currently is a deep lack of knowledge. METHODS We conducted a retrospective cohort study using data from an administrative claims database between January 1, 2004 and December 31, 2010. Patients were included into the study if they had at least two malignant primary cancer diagnoses codes (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]: 140-209 [not including 196-199.0]) from the same cancer site and a prescription for a VEGF inhibitor. We estimated the incidence rate (IR) and 95% confidence interval (CI) for each adverse event under study. RESULTS 2326 patients met the inclusion and exclusion criteria. The mean age for the cohort was 57.3 where 79% of the patients were 50 years of age or older. The most common adverse event was nausea and vomiting (IR = 651.7/1000 person-years; 95% CI = 589.7-718.4). Other common adverse events were hypertension (IR = 452.9/1000 person-years; 95% CI = 394.9-517.1) and hemorrhage (IR = 375.2/1000 person-years; 95% CI = 332.2-422.3). The least common adverse events were rare dermatologic diseases such as Stevens-Johnson syndrome and toxic epidermal necrolysis where no cases were observed. CONCLUSIONS The rates detailed in this analysis are helpful in understanding the benefit risk of VEGF inhibitors as they are prescribed in the real world. Although no formal comparisons were conducted, the VEGF inhibitors evaluated in this study appeared to have overlapping toxicity profiles; however, the manner in which these AEs are listed in the prescribing information was not always consistent.

Cardiovascular Outcomes Associated with Lowering Low-density Lipoprotein Cholesterol in Rheumatoid Arthritis and Matched Nonrheumatoid Arthritis

Objective. To examine the associations between lowering low-density lipoprotein cholesterol (LDL-C) and cardiovascular (CV) outcomes among patients with rheumatoid arthritis (RA) and patients without it. Methods. Adult patients with RA and 2 age- and sex-matched control cohorts [RA plus general controls (RA/GN), RA plus osteoarthritis (OA) controls (RA/OA)] were identified between January 1, 2007, and December 31, 2011. Patients with a diagnosis of hyperlipidemia who initiated statin therapy without prior CV events were included. Multivariable Cox proportional hazard analyses were used. Results. The study identified 1522 patients with RA with 6511 general controls (RA/GN cohort); and 1746 patients with RA with 2554 OA controls (RA/OA cohort). During followup, mean (SD) LDL-C (mg/dl) was 96.8 (32.7) for RA, 100.1 (35.1) for general controls, and 99.1 (34.3) for OA. The relationship between lowering LDL-C and CV outcomes was similar for both RA and non-RA controls (p for interaction = 0.852 in RA/GN cohort, and p = 0.610 in RA/OA cohort). After adjusting for baseline CV risk factors, lowering LDL-C was associated with a 29%–50% lower risk of CV events (HR [95% CI] = 0.71 [0.57–0.89] in RA/GN, 0.50 [0.43–0.58] in RA/OA). Subgroup analyses showed that lowering LDL-C was associated with a similar degree of reduction of CV events in RA and non-RA controls (HR of 0.67–0.68 for RA, 0.72 for general controls, 0.76 for OA controls). Conclusion. Lowering LDL-C levels was associated with reduced CV events. The relationship between lowering LDL-C and CV outcomes in RA was similar to the relationship found in matched general and OA controls.

ASSOCIATION BETWEEN HYPOGLYCEMIA AND FALL-RELATED FRACTURES AND HEALTH CARE UTILIZATION IN OLDER VETERANS WITH TYPE 2 DIABETES.

OBJECTIVE To examine the association between hypoglycemia and fall-related outcomes in older patients with type 2 diabetes mellitus (T2DM). METHODS This retrospective cohort study used electronic medical records of T2DM patients (≥65 years) from the Veterans Integrated Service Network 16 (VISN 16) data warehouse (01/01/2004-06/30/2010). Patients in nonhypoglycemia group (non-HG) were 1:1 randomly matched with patients in hypoglycemia group (HG) by age (±5 years), sex, race, and medical center location. Fall-related events (i.e., fractures and head injuries) were identified, with a fall being the external cause within ±2 days. McNemar tests and generalized estimating equation (GEE) models were used to compare fall-related events in the 1-year outcome period after the index date (i.e., date of first hypoglycemic episode). We also examined fall-related healthcare utilization. RESULTS A total of 4,215 patients in each group were studied, with the mean age of 76.5 years (SD: 5.85). The mean Charlson comorbidity index (CCI) scores were 5.73 (SD: 2.95) in the HG and 4.34 (SD: 2.40) in the non-HG. The HG had significantly higher rates of fall-related events than non-HG, 27 (0.64%) versus 1 (0.02%) and 89 (2.11%) versus 21 (0.50%) events within 30 days and 1 year, respectively. GEE models confirmed the elevated risk of fall-related events after controlling for sociodemographic and clinical characteristics, comorbidities, and medication use (adjusted odds ratio [aOR]: 2.70; 95% confidence interval [CI]: 1.64-4.47). The HG patients were more likely to have emergency department (ED) visits, hospital admissions, and long-term care placement compared to their counterparts. CONCLUSION Hypoglycemia is associated with worse fall-related outcomes among the elderly veterans.

Traditional Cardiovascular Disease Risk Factor Management in Rheumatoid Arthritis Compared to Matched Nonrheumatoid Arthritis in a US Managed Care Setting.

To compare traditional cardiovascular (CV) risk factor management among patients with rheumatoid arthritis (RA) to that of matched non‐RA controls within a large US managed care setting.

Effects of Achieving Target Measures in RA on Functional Status, Quality of Life and Resource Utilization: Analysis of Clinical Practice Data

To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study.

Effects of Achieving Target Measures in Rheumatoid Arthritis on Functional Status, Quality of Life, and Resource Utilization: Analysis of Clinical Practice Data.

To evaluate associations between achieving guideline‐recommended targets of disease activity, defined by the Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) <2.6, the Simplified Disease Activity Index (SDAI) ≤3.3, or the Clinical Disease Activity Index (CDAI) ≤2.8, and other health outcomes in a longitudinal observational study.

Venous thromboembolism prophylaxis and clinical consequences in medically ill patients.

The objective of this study was to examine venous thromboembolism (VTE) prophylaxis use, risk reduction, and readmission in medically ill patients during hospitalization and after discharge. This 5-year retrospective study linked outpatient files from MarketScan Commercial and Medicare Supplemental databases. Patients were categorized into prophylaxis and non-prophylaxis groups based on guideline-recommended anticoagulant use from the index date to 180 days posthospital discharge and before the first VTE event date. Outcome variables were VTE events and rehospitalization. Risk adjustment was conducted within the prophylaxis group and between the prophylaxis and non-prophylaxis groups using propensity score matching. Among 4467 patients, 28.99% of the patients (n = 1295) were admitted with cancer, 18.03% (n = 805) with pneumonia, 14.06% (n = 628) with heart failure, 11.06% (n = 494) with stroke, 11.11% (n = 496) with sepsis, 8.08% (n = 361) with infectious diseases, 5.6% (n = 250) with severe respiratory disorders, 1.81% (n = 81) with inflammatory bowel disease, 1.05% (n = 47) with obesity, 0.20% (n = 9) with neurologic disorders, and 0.02% (n = 1) with acute rheumatic fever. Among those with 180-day continuous enrollment after the index date (n = 3511), 51.81% (n = 1819) received anticoagulant therapy only, 2.48% (n = 87) received mechanical compression treatment only (stocking or pneumatic compression), and 4.41% (n = 155) received both during hospitalization. Anticoagulant therapy rates ranged from 88.64% (obesity) to 32.39% (inflammatory bowel disease). Among anticoagulant therapy patients, 740 patients (40.68%) received low–molecular weight heparin only and 806 patients (44.31%) received unfractionated heparin. After risk adjustment, compared with patients without VTE prophylaxis, anticoagulant prophylaxis patients had lower VTE (3.62% vs. 4.27%, P < 0.04) and readmission rates (24.22% vs. 27.95%, P < 0.02) during the 6 months post-index hospital admission. In conclusion anticoagulant prophylaxis is underutilized and is associated with reduced VTE risk and a decrease in rehospitalizations for medically ill patients.