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Phoenix, AZ, United States

Cohen A.L.,Banner Good Samaritan Medical Center | Sarid R.,Phoenix VA Health Care System
Thrombosis Research | Year: 2010

Introduction: Monoclonal gammopathy of undetermined significance (MGUS) has been proposed to be a risk factor for venous thromboembolic disease (VTE). However, no series published to date has been population-based or included a control group with similar comorbidities to people with MGUS. Patients/Methods: We reviewed the records of all the male veterans in a single VA healthcare system with MGUS between January 1, 1996 and December 31, 2005. We compared the rate of VTE in 166 patients with MGUS with the rate of VTE in an age-matched control group of 465 patients who had tested negative for monoclonal gammopathy by serum protein electrophoresis (SPEP). Results: The VTE rate in the MGUS group was 2.2 per 100 person-years, which was not significantly different from the rate in the control group, 1.4 per 100 person-years (HR 1.38, CI 0.63-3.01, p = 0.42). Most VTE events occurred within 4 months of the diagnosis of MGUS. In univariate analysis, albumin level (HR 0.21, CI 0.1-0.41, p < 0.001), abnormal leukocyte count (HR 2.53, CI 1.09-5.86, p = 0.03), and history of prior VTE (HR 4.41, CI 1.69-11.54, p = 0.003) were associated with increased risk of VTE. On multivariate analysis, albumin level and history of prior VTE remained significant, but presence of MGUS was still not significantly associated with VTE risk. Conclusion: Our results suggest that the increased rate of VTE in people with MGUS may be primarily due to other underlying conditions that led to testing for a monoclonal gammopathy rather than to the monoclonal gammopathy itself. © 2009 Elsevier Ltd. Source

Dev S.,Phoenix VA Health Care System | Clare R.M.,Duke Clinical Research Institute | Felker G.M.,Duke Clinical Research Institute | Fiuzat M.,Duke Clinical Research Institute | And 2 more authors.
European Journal of Heart Failure | Year: 2012

Aims Survival preferences, ascertained from time-trade-off utilities, have not been studied in heart failure patients who designate a 'do not resuscitate' (DNR) status. Therefore, the aim of this study was to determine the association of heart failure patients resuscitation preferences with survival preferences and mortality in the ESCAPE trial. Methods and results We analysed the association of resuscitation orders at 1 month with time-trade-off utilities and 6-month mortality. There were 26 and 349 patients with a DNR order and Full Code order, respectively. DNR patients were older, had more coronary artery disease, hypertension, renal impairment, and poorer exercise capacity than Full Code patients. DNR patients also experienced longer hospitalization and higher 6-month mortality. In multivariate analysis, DNR preference was associated with 10-fold higher odds of willingness to trade survival time (lower time-trade-off utility) in favour of improved quality of life [odds ratio 10.33, 95 confidence interval (CI) 1.6564.80]. DNR preference was the best predictor of mortality (χ 2 26.12, P < 0.0001, hazard ratio 6.88, 95 CI 3.2814.41), despite adjustment for known predictors including brain natriuretic peptide. Conclusions Heart failure patients requests to forgo resuscitation may signify more than simply 'what-if' directives for emergency care. DNR decisions may reflect preferences for intervention to enhance quality rather than prolong survival, which is particularly important as these patients have high early mortality. © 2011 The Author. Source

Saremi A.,Phoenix VA Health Care System | Bahn G.,Cooperative Studies Program Coordinating Center | Reaven P.D.,Phoenix VA Health Care System
Diabetes Care | Year: 2012

OBJECTIVE - To determine the effect of statin use on progression of vascular calcification in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS - Progression of coronary artery calcification (CAC) and abdominal aortic artery calcification (AAC) was assessed according to the frequency of statin use in 197 participants with T2DM. RESULTS - After adjustment for baseline CAC and other confounders, progression of CAC was significantly higher in more frequent statin users than in less frequent users (mean ± SE, 8.2 ± 0.5 mm 3 vs. 4.2 ± 1.1 mm3; P < 0.01). AAC progression was in general not significantly increased with more frequent statin use; in a subgroup of participants initially not receiving statins, however, progression of both CAC and AAC was significantly increased in frequent statin users. CONCLUSIONS - More frequent statin use is associated with accelerated CAC in T2DM patients with advanced atherosclerosis. © 2012 by the American Diabetes Association. Source

Goldfine A.B.,Harvard University | Conlin P.R.,Brigham and Womens Hospital | Halperin F.,Harvard University | Koska J.,Phoenix VA Health Care System | And 5 more authors.
Diabetologia | Year: 2013

Aims/hypothesis: Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance. Methods: We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment. Results: Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI -39%, 56%]; placebo 6% [95% CI -20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (-16% vs 42%, p = 0.005), but was not correlated with metabolic improvements. The frequency of tinnitus was low but tended to be higher with salsalate therapy (n = 4 vs n = 2). Conclusions/interpretation: In summary, salsalate therapy was well tolerated, lowered fasting glucose, increased adiponectin and reduced adipose tissue NF-κB activity. These changes were not related to changes in peripheral insulin sensitivity, suggesting additional mechanisms for metabolic improvement. Trial registration: ClinicalTrials.gov NCT00330733 Funding: Office of Research and Development, Medical Research Service, Department of Veterans Affairs and NIH K24 DK63214 © 2013 Springer-Verlag (outside the USA). Source

Saremi A.,Phoenix VA Health Care System | Bahn G.D.,Cooperative Studies Program Coordinating Center | Reaven P.D.,Phoenix VA Health Care System
Diabetes Care | Year: 2016

OBJECTIVE To determine whether a link exists between serious hypoglycemia and progression of atherosclerosis in a substudy of the Veterans Affairs Diabetes Trial (VADT) and to examine whether glycemic control during the VADT modified the association between serious hypoglycemia and coronary artery calcium (CAC) progression. RESEARCH DESIGN AND METHODS Serious hypoglycemia was defined as severe episodes with loss of consciousness or requiring assistance or documented glucose <50 mg/dL. Progression of CAC was determined in 197 participants with baseline and follow-up computed tomography scans. RESULTS During an average follow-up of 4.5 years between scans, 97 participants reported severe hypoglycemia (n = 23) or glucose <50mg/dL (n = 74). Serious hypoglycemia occurred more frequently in the intensive therapy group than in the standard treatment group (74%vs. 21%, P <0.01). Serious hypoglycemiawas not associated with progression of CAC in the entire cohort, but the interaction between serious hypoglycemia and treatment was significant (P <0.01). Participants with serious hypoglycemia in the standard therapy group, but not in the intensive therapy group, had ∼50% greater progression of CAC than those without serious hypoglycemia (median 11.15 vs. 5.4 mm 3, P = 0.02). Adjustment for all baseline differences, including CAC, or time-varying risk factors during the trial, did not change the results. Examining the effect of serious hypoglycemia by on-trial HbA1c levels (cutoff 7.5%) yielded similar results. In addition, a dose-response relationship was found between serious hypoglycemia and CAC progression in the standard therapy group only. CONCLUSIONS Despite a higher frequency of serious hypoglycemia in the intensive therapy group, serious hypoglycemia was associated with progression of CAC in only the standard therapy group. © 2016 by the American Diabetes Association. Source

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