Albuquerque, NM, United States
Albuquerque, NM, United States

Time filter

Source Type

Peduzzi P.,U S WEST | Kyriakides T.,U S WEST | O'Connor T.Z.,U S WEST | Guarino P.,U S WEST | And 2 more authors.
American Journal of Medicine | Year: 2010

The US Department of Veterans Affairs (VA) Cooperative Studies Program has been conducting comparative effectiveness clinical trials for nearly 4 decades in many disease areas, including cardiovascular disease/surgery, diabetes mellitus, mental health, neurologic disorders, cancer, infectious diseases, and rheumatoid arthritis. The features that have made this program advantageous for conducting comparative effectiveness clinical trials are described along with methodological considerations for future trials based on lessons learned from its experience conducting these types of studies. Some of the lessons learned involve managing risk factors, clinical equipoise, patient preferences, evolving technology, the use of usual care as a comparator and pharmaceutical issues related to study drug blinding. These issues are not unique to the VA but can play an important role in enabling valid comparisons between treatments that may have differences in delivery or mechanisms of action and could affect the execution and feasibility of conducting a clinical trial with a comparative effectiveness aim. We also outline some future directions for comparative effectiveness clinical trials. © 2010 Elsevier Inc. All rights reserved.


McFall M.,Veterans Affairs Puget Sound Health Care System | McFall M.,University of Washington | Saxon A.J.,Veterans Affairs Puget Sound Health Care System | Saxon A.J.,University of Washington | And 16 more authors.
JAMA - Journal of the American Medical Association | Year: 2010

Context: Most smokers with mental illness do not receive tobacco cessation treatment. Objective: To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder (PTSD) improves longterm smoking abstinence rates. Design, Setting, and Patients: A randomized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009. Intervention: Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians (integrated care [IC]) vs referral to Veterans Affairs smoking cessation clinics (SCC). Patients received smoking cessation treatment within 3 months of study enrollment. Main Outcome Measures Smoking outcomes included 12-month bioverified prolonged abstinence (primary outcome) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals. Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome. Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Questionnaire 9, respectively, to determine if IC participation or quitting smoking worsened psychiatric status. Results: Integrated care was better than SCC on prolonged abstinence (8.9% vs 4.5%; adjusted odds ratio, 2.26; 95% confidence interval [CI], 1.30-3.91; P=.004). Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence (78/472 [16.5%] vs 34/471 [7.2%], P<.001) and remained significant at 18 months (86/472 [18.2%] vs 51/471 [10.8%], P<.001). Number of counseling sessions received and days of cessation medication used explained 39.1% of the treatment effect. Between baseline and 18 months, psychiatric status did not differ between treatment conditions. Posttraumatic stress disorder symptoms for quitters and nonquitters improved. Nonquitters worsened slightly on the Patient Health Questionnaire 9 relative to quitters (differences ranged between 0.4 and 2.1, P=.03), whose scores did not change over time. Conclusion: Among smokers with military-related PTSD, integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment resulted in greater prolonged abstinence. Trial Registration clinicaltrials.gov Identifier: NCT00118534 ©2010 American Medical Association. All rights reserved.


Matchar D.B.,Duke University | Matchar D.B.,National University of Singapore | Jacobson A.,Loma Linda University | Dolor R.,Duke University | And 11 more authors.
New England Journal of Medicine | Year: 2010

BACKGROUND: Warfarin anticoagulation reduces thromboembolic complications in patients with atrial fibrillation or mechanical heart valves, but effective management is complex, and the international normalized ratio (INR) is often outside the target range. As compared with venous plasma testing, point-of-care INR measuring devices allow greater testing frequency and patient involvement and may improve clinical outcomes. METHODS: We randomly assigned 2922 patients who were taking warfarin because of mechanical heart valves or atrial fibrillation and who were competent in the use of point-ofcare INR devices to either weekly self-testing at home or monthly high-quality testing in a clinic. The primary end point was the time to a first major event (stroke, major bleeding episode, or death). RESULTS: The patients were followed for 2.0 to 4.75 years, for a total of 8730 patient-years of follow-up. The time to the first primary event was not significantly longer in the self-testing group than in the clinic-testing group (hazard ratio, 0.88; 95% confidence interval, 0.75 to 1.04; P = 0.14). The two groups had similar rates of clinical outcomes except that the self-testing group reported more minor bleeding episodes. Over the entire follow-up period, the self-testing group had a small but significant improvement in the percentage of time during which the INR was within the target range (absolute difference between groups, 3.8 percentage points; P<0.001). At 2 years of follow-up, the self-testing group also had a small but significant improvement in patient satisfaction with anticoagulation therapy (P = 0.002) and quality of life (P<0.001). CONCLUSIONS: As compared with monthly high-quality clinic testing, weekly self-testing did not delay the time to a first stroke, major bleeding episode, or death to the extent suggested by prior studies. These results do not support the superiority of self-testing over clinic testing in reducing the risk of stroke, major bleeding episode, and death among patients taking warfarin therapy. (Funded by the Department of Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT00032591.). Copyright © 2010 Massachusetts Medical Society.


Raisch D.W.,University of New Mexico | Raisch D.W.,Clinical Research Pharmacy Coordinating Center | Feeney P.,Wake forest University | Goff Jr D.C.,Wake forest University | And 5 more authors.
Cardiovascular Diabetology | Year: 2012

Background: Health utility (HU) measures are used as overall measures of quality of life and to determine quality adjusted life years (QALYs) in economic analyses. We compared baseline values of three HUs including Short Form 6 Dimensions (SF-6D), and Health Utilities Index, Mark II and Mark III (HUI2 and HUI3) and the feeling thermometer (FT) among type 2 diabetes participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. We assessed relationships between HU and FT values and patient demographics and clinical variables.Methods: ACCORD was a randomized clinical trial to test if intensive controls of glucose, blood pressure and lipids can reduce the risk of major cardiovascular disease (CVD) events in type 2 diabetes patients with high risk of CVD. The health-related quality of life (HRQOL) sub-study includes 2,053 randomly selected participants. Interclass correlations (ICCs) and agreement between measures by quartile were used to evaluate relationships between HU's and the FT. Multivariable regression models specified relationships between patient variables and each HU and the FT.Results: The ICCs were 0.245 for FT/SF-6D, 0.313 for HUI3/SF-6D, 0.437 for HUI2/SF-6D, 0.338 for FT/HUI2, 0.337 for FT/HUI3 and 0.751 for HUI2/HUI3 (P < 0.001 for all). Common classification by quartile was found for the majority (62%) of values between HUI2 and HUI3, which was significantly (P < 0.001) higher than between other HUs and the FT: SF-6D/HUI3 = 40.8%, SF-6D/HUI2 = 40.9%, FT/HUI3 = 35.0%, FT/HUI2 = 34.9%, and FT/SF-6D = 31.9%. Common classification was higher between SF-6D/HUI2 and SF-6D/HUI3 (P < 0.001) than between FT/SF-6D, FT/HUI2, and FT/HUI3. The mean difference in HU values per patient ranged from -0.024 ± 0.225 for SF-6D/ HUI3 to -0.124 ± 0.133 for SF-6D/HUI2. Regression models were significant; clinical and demographic variables explained 6.1% (SF-6D) to 7.7% (HUI3) of the variance in HUs.Conclusions: The agreements between the different HUs were poor except for the two HUI measures; therefore HU values derived different measures may not be comparable. The FT had low agreement with HUs. The relationships between HUs and demographic and clinical measures demonstrate how severity of diabetes and other clinical and demographic factors are associated with HUs and FT measures.Trial registration: ClinicalTrials.gov Identifier: NCT00000620. © 2012 Raisch et al.; licensee BioMed Central Ltd.


Snodgrass A.J.,Clinical Research Pharmacy Coordinating Center | Campbell H.M.,Clinical Research Pharmacy Coordinating Center | Mace D.L.,Clinical Research Pharmacy Coordinating Center | Faria V.L.,Veterans Affairs Palo Alto Heath Care System | And 3 more authors.
Pharmacotherapy | Year: 2010

The phosphodiesterase type 5 (PDE-5) inhibitors-sildenafil, vardenafil, and tadalafil-are used primarily in erectile dysfunction, but sildenafil is also indicated for pulmonary hypertension. Common adverse effects of vardenafil include headache, flushing, nasal congestion, dyspepsia, and nausea. Recently, PDE-5 inhibitors have been associated with adverse vision effects, and emerging evidence now indicates that they may also be responsible for hearing changes and hearing loss. We describe a patient who developed unilateral sudden sensorineural hearing loss possibly related to the use of vardenafil for erectile dysfunction. To our knowledge, only one other case of hearing loss related to this drug class has been published. Our patient was a 57-year-old man who came to the emergency department with right-sided mild-to-moderate hearing loss in the 500-3000-Hz range, confirmed by audiogram, that occurred after ingestion of vardenafil. The patient was hospitalized 2 days later for administration of intravenous dexamethasone, followed by oral prednisone. He reported that his hearing had improved on the fourth hospital day and was discharged 3 days later, continuing to taper the prednisone on an outpatient basis. A repeat audiogram after 10 days of corticosteroid therapy confirmed that his hearing in the 500-3000-Hz range was within normal limits. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 3) adverse reaction of sudden sensorineural hearing loss associated with vardenafil consumption. We also performed an analysis of hearing loss cases related to PDE-5 inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System database to compare the characteristics of our patient with those of other reported adverse event cases. Based on the temporal relation of the sudden sensorineural hearing loss to this patient's drug consumption, we propose that the vardenafil is a likely cause of the hearing loss. This case provides further evidence that PDE-5 inhibitor consumption should be considered as a possible cause in patients presenting with sudden sensorineural hearing loss.


Duckworth W.C.,Phoenix Health Care Center | Abraira C.,Miami Medical Center | Moritz T.E.,Csp Inc. | Davis S.N.,Tennessee Valley Health Care System | And 9 more authors.
Journal of Diabetes and its Complications | Year: 2011

Background: The goal of the VA Diabetes Trial (VADT) was to determine the effect of intensive glucose control on macrovascular events in subjects with difficult-to-control diabetes. No significant benefit was found. This report examines predictors of the effect of intensive therapy on the primary outcome in this population. Methods: This trial included 1791 subjects. Baseline cardiovascular risk factors were collected by interview and the VA record. The analyses were done by intention to treat. Findings: Univariate analysis at baseline of predictors of a primary cardiovascular (CV) event included a prior CV event, age, insulin use at baseline, and duration of diagnosed diabetes (all P<.0001). Multivariable modeling revealed a U-shaped relationship between duration of diabetes and treatment. Modeled estimates for the hazard ratios (HRs) for treatment show that subjects with a short duration (3 years or less) of diagnosed diabetes have a nonsignificant increase in risk (HR >1.0) after which the HR is below 1.0. From 7 to 15 years' duration at entry, subjects have HRs favoring intensive treatment. Thereafter the HR approaches 1.0 and over-21-years' duration approaches 2.0. Duration over 21 years resulted in a HR of 1.977 (CI 1.77-3.320, P<.01). Baseline c-peptide levels progressively declined up to 15 years and were stable subsequently. Interpretation: In difficult-to-control older subjects with type 2 DM, duration of diabetes altered the response to intensive glucose control. Intensive therapy may reduce CV events in subjects with a duration of 15 years or less and may increase risks in those with longer duration. © 2011 Elsevier Inc. All rights reserved.


PubMed | University of Houston, University of Illinois at Chicago, University of Colorado at Denver and Clinical Research Pharmacy Coordinating Center
Type: Journal Article | Journal: Current therapeutic research, clinical and experimental | Year: 2014

Although corticosteroids such as prednisone are efficacious for the treatment of severe asthma, chronic administration of oral corticosteroid therapy is associated with significant adverse effects. Previous studies have shown that clarithromycin is effective in reducing bronchial hyperresponsiveness and allergen-induced bronchoconstriction. However, the effect of long-term clarithromycin therapy in patients with prednisone-dependent asthma is uncertain.This study was conducted to determine the effects of oral clarithromycin on prednisone daily dosage, pulmonary function, quality of life (QOL), and asthmatic symptoms in patients with corticosteroid-dependent asthma.This 14-week, prospective, randomized, double-blind, placebo-controlled pilot study was conducted at Pulmonary Associates (Phoenix, Arizona) and the University of Illinois at Chicago Medical Center (Chicago, Illinois). Patients aged 18 to 75 years with an established diagnosis of asthma and who had been receiving 5 mg/d of prednisone for the preceding 6 months were enrolled. After a 4-week data-collection period, patients received clarithromycin 500 mg BID for 6 weeks, followed by a 4-week follow-up period. The effects of clarithromycin therapy on prednisone dosage requirements, pulmonary function (as assessed using spirometry), QOL, and asthmatic symptoms (nocturnal asthma, shortness of breath, chest discomfort, wheezing, and cough) were assessed.Fourteen patients (9 men, 5 women; mean [SD] age, 62 [13] years) completed the study and were included in the final analysis. One patient withdrew from the study due to clarithromycin-related nausea. After 6 weeks of clarithromycin therapy, patients were able to tolerate a significant reduction in mean (SD) prednisone dosage from baseline (30% [18%]; P- 0.020). Pulmonary function, QOL, and asthmatic symptoms did not significantly worsen despite reduction in prednisone dose. All patients who completed the study tolerated clarithromycin therapy.In this pilot study of patients with corticosteroid-dependent asthma, 6-week clarithromycin 500 mg BID was clinically effective in allowing a reduction in prednisone dosage, without worsening pulmonary function, QOL, or asthmatic symptoms. In addition, clarithromycin was well tolerated, with only 1 patient discontinuing therapy due to treatment-related nausea.


Sullivan M.D.,University of Washington | O'Connor P.,HealthPartners | Feeney P.,Wake forest University | Hire D.,Wake forest University | And 8 more authors.
Diabetes Care | Year: 2012

OBJECTIVE - Depression affects up to 20-25% of adults with type 2 diabetes and may increase all-cause mortality, but few well-designed studies have examined the effects of depression on the full range of cardiovascular disease outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS - A total of 2,053 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) Health-Related Quality of Life substudy completed the Patient Health Questionnaire (PHQ)-9 measure of depression symptoms at baseline and 12, 36, and 48 months. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% CI) for the time-varying impact of depression on protocol-defined clinical outcomes with and without adjustment for demographic, trial-related, clinical, and behavioral variables. RESULTS - In fully adjusted models, depression was not significantly related to the ACCORD primary composite outcome (cardiovascular death, nonfatal heart attack, or stroke) (HR 1.53 [95% CI 0.85-2.73]) or to the ACCORD microvascular composite outcome (0.93 [0.53-1.62]), but all-cause mortality was significantly increased both in those with PHQ-assessed probable major depression (2.24 [1.24-4.06]) and PHQ score of ≥10 (1.84 [1.17-2.89]). The effect of depression on all-cause mortality was not related to previous cardiovascular events or to assignment to intensive or standard glycemia control. Probable major depression (by PHQ-9) had a borderline impact on the ACCORD macrovascular end point (1.42 [0.99-2.04]). CONCLUSIONS - Depression increases the risk of all-causemortality andmay increase the risk of macrovascular events among adults with type 2 diabetes at high risk for cardiovascular events. © 2012 by the American Diabetes Association.


Snodgrass A.J.,Clinical Research Pharmacy Coordinating Center | Campbell H.M.,Clinical Research Pharmacy Coordinating Center | Mace D.L.,Clinical Research Pharmacy Coordinating Center | Faria V.L.,Clinical Research Pharmacy Coordinating Center | And 2 more authors.
Pharmacotherapy | Year: 2010

The phosphodiesterase type 5 (PDE-5) inhibitors-sildenafil, vardenafil, and tadalafil-are used primarily in erectile dysfunction, but sildenafil is also indicated for pulmonary hypertension. Common adverse effects of vardenafil include headache, flushing, nasal congestion, dyspepsia, and nausea. Recently, PDE-5 inhibitors have been associated with adverse vision effects, and emerging evidence now indicates that they may also be responsible for hearing changes and hearing loss. We describe a patient who developed unilateral sudden sensorineural hearing loss possibly related to the use of vardenafil for erectile dysfunction. To our knowledge, only one other case of hearing loss related to this drug class has been published. Our patient was a 57-year-old man who came to the emergency department with right-sided mild-to-moderate hearing loss in the 500-3000-Hz range, confirmed by audiogram, that occurred after ingestion of vardenafil. The patient was hospitalized 2 days later for administration of intravenous dexamethasone, followed by oral prednisone. He reported that his hearing had improved on the fourth hospital day and was discharged 3 days later, continuing to taper the prednisone on an outpatient basis. A repeat audiogram after 10 days of corticosteroid therapy confirmed that his hearing in the 500-3000-Hz range was within normal limits. Use of the Naranjo adverse drug reaction probability scale indicated a possible (score of 3) adverse reaction of sudden sensorineural hearing loss associated with vardenafil consumption. We also performed an analysis of hearing loss cases related to PDE-5 inhibitors in the United States Food and Drug Administration's Adverse Event Reporting System database to compare the characteristics of our patient with those of other reported adverse event cases. Based on the temporal relation of the sudden sensorineural hearing loss to this patient's drug consumption, we propose that the vardenafil is a likely cause of the hearing loss. This case provides further evidence that PDE-5 inhibitor consumption should be considered as a possible cause in patients presenting with sudden sensorineural hearing loss.


PubMed | Clinical Research Pharmacy Coordinating Center
Type: Comparative Study | Journal: Clinical trials (London, England) | Year: 2013

Assessment of adherence to study medications is a common challenge in clinical research. Counting unused study medication is the predominant method by which adherence is assessed in outpatient clinical trials but it has limitations that include questionable validity and burdens on research personnel.To compare capsule counts, patient questionnaire responses, and plasma drug levels as methods of determining adherence in a clinical trial that had 2056 participants and used centralized drug distribution and patient follow-up.Capsule counts from study medication bottles returned by participants and responses to questions regarding adherence during quarterly telephone interviews were averaged and compared. Both measures were compared to plasma drug levels obtained at the 3-month study visit of patients in the treatment group. Counts and questionnaire responses were converted to adherence rates (doses taken divided by days elapsed) and were categorized by stringent (85.7%) and liberal (71.4%) definitions. We calculated the prevalence-adjusted bias-adjusted kappa to assess agreement between the two measures.Using a pre-paid mailer, participants returned 76.0% of study medication bottles to the central pharmacy. Both capsule counts and questionnaire responses were available for 65.8% of participants and were used to assess adherence. Capsule counts identified more patients who were under-adherent (18.8% by the stringent definition and 7.5% by the liberal definition) than self-reports did (10.4% by the stringent definition and 2.1% by the liberal definition). The prevalence-adjusted bias-adjusted kappa was 0.58 (stringent) and 0.83 (liberal), indicating fair and very good agreement, respectively. Both measures were also in agreement with plasma drug levels determined at the 3-month visit (capsule counts: p=0.005 for the stringent and p=0.003 for the liberal definition; questionnaire: p=0.002 for both adherence definitions).Inconsistent bottle returns and incomplete notations of medication start and stop dates resulted in missing data but exploratory missing data analyses showed no reason to believe that the missing data resulted in systematic bias.Depending upon the definition of adherence, there was fair to very good agreement between questionnaire results and capsule counts among returned study bottles, confirmed by plasma drug levels. We conclude that a self-report of medication adherence is potentially comparable to capsule counts as a method of assessing adherence in a clinical trial, if a relatively low adherence threshold is acceptable, but adherence should be confirmed by other measures if a high adherence threshold is required.

Loading Clinical Research Pharmacy Coordinating Center collaborators
Loading Clinical Research Pharmacy Coordinating Center collaborators