Sanjay K. Gandhi

Psychometric Evaluation of the 12-Item Short-Form Health Survey (SF-12) in Osteoarthritis and Rheumatoid Arthritis Clinical Trials

BACKGROUND The psychometric properties of the 12-Item Short-Form Health Survey (SF-12), a subset of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), have been tested in the general population and certain disease states. OBJECTIVE The purpose of this study was to evaluate the psychometric properties of the SF-12 as a generic measure of health-related quality of life (HRQoL) in osteoarthritis (OA) and rheumatoid arthritis (RA) patient populations in clinical trials. METHODS Data were aggregated from 5 clinical trials evaluating the efficacy of non-steroidal anti-inflammatory drugs in OA (n = 651) and RA (n = 693) patients. Patient assessments in these trials were made using the SF-36 and commonly used clinical measures of OA and RA at baseline and after up to 6 weeks of treatment. For the items of the SF-36 contained in the SF-12, the item missing rate, computability of scores, floor and ceiling effects, factor structure, and item-component correlations were evaluated. Clinical variables and correlations of physical component summary (PCS-12) and mental component summary (MCS-12) scores of the SF-12 with the corresponding SF-36 component summary scores (PCS-36 and MCS-36) were also examined. Analyses were conducted separately for OA and RA patients. RESULTS A low individual SF-12 item missing rate (0.29% to 2.30%) and a high percentage score computability (90.9%-94.3%) were observed at baseline. No floor or ceiling effects at baseline were observed. The scree plot confirmed the 2-factor structure of the SF-12 items. Items belonging to the physical component correlated more strongly with the PCS-12 than with the MCS-12; similarly, items belonging to the mental component correlated more strongly with the MCS-12 than with the PCS-12. The correlations between the PCS-12 and PCS-36 and between the MCS-12 and MCS-36 ranged from 0.92 to 0.96 (P < 0.001) at baseline and at week 2, 4, or 6. Significant correlations ranging from -0.09 to -0.58 (P < 0.05) were observed between the SF-12 scores and clinical variables. CONCLUSION The SF-12 appears to be a psychometrically sound tool for the assessment of HRQoL in OA and RA patients.

The prevalence of coronary artery calcium among diabetic individuals without known coronary artery disease

OBJECTIVES We sought to examine the age and gender distribution of coronary artery calcium (CAC) by diabetes status in a large cohort of asymptomatic individuals. BACKGROUND Among individuals with diabetes, coronary artery disease (CAD) is a major cause of morbidity and mortality. Electron-beam tomography (EBT) quantifies CAC, a marker for atherosclerosis. METHODS Screening for CAC by EBT was performed in 30,904 asymptomatic individuals stratified by their self-reported diabetes status, gender, and age. The distribution of CAC across the strata and the association between diabetes and CAC were examined. RESULTS Compared with nondiabetic individuals (n = 29,829), those with diabetes (n = 1,075) had higher median CAC scores across all but two age groups (women 40 to 44 years old and men and women > or =70 years old). Overall, the likelihood of having a CAC score in the highest age/gender quartile was 70% greater for diabetic individuals than for their nondiabetic counterparts. CONCLUSIONS Younger diabetic individuals appear to have calcified plaque burden comparable to that of older individuals without diabetes. These findings call for future research to determine if EBT-CAC screening has an incremental value over the current CAD risk assessment of individuals with diabetes.

Similarity as a risk factor in drug-name confusion errors: the look-alike (orthographic) and sound-alike (phonetic) model.

BACKGROUND One of every four medication errors reported in the United States is a name-confusion error. The rate of name-confusion errors might be reduced if new and confusing names were not allowed on the market and if safeguards could be put in place to avoid confusion between existing names. OBJECTIVES To evaluate several prognostic tests of drug-name confusion, alone and in combination, with respect to their sensitivity, specificity, and overall accuracy. RESEARCH DESIGN Case-control study. Twenty-two different computerized measures of orthographic similarity, orthographic distance, and phonetic similarity were used to compute similarity/distance scores for n = 1,127 cases (ie, pairs of names that appeared in published error reports or national error databases) and n = 1,127 controls. MAIN OUTCOME MEASURES Mean similarity/distance scores were compared across cases and controls. The performance of each measure at distinguishing between cases and controls was evaluated by tenfold crossvalidation. Dose-response relationships were examined. Univariate and multivariate logistic regression models were formed and evaluated by 10 fold crossvalidation. RESULTS Cases had significantly higher similarity scores than controls. Every measure of similarity proved to be a significant risk factor for error. There was a significant increasing trend in the odds-ratio as a function of similarity. A three-predictor logistic regression model had crossvalidated sensitivity of 93.7%, specificity of 95.9% and accuracy of 94.8%. CONCLUSIONS A sensitive and specific test of drug-name confusion potential can be formed using objective measures of orthographic similarity, orthographic distance, and phonetic distance.

Effect of Rosuvastatin Compared with Other Statins on Lipid Levels and National Cholesterol Education Program Goal Attainment for Low-Density Lipoprotein Cholesterol in a Usual Care Setting

Study Objective. To compare, in a usual care setting, the effects of rosuvastatin and other 3‐hydroxy‐3‐methylglutaryl coenzyme A inhibitors (statins) on lipid levels and on goal attainment of low‐density lipoprotein cholesterol (LDL) levels from the National Cholesterol Education Program (NCEP) third report of the Adult Treatment Panel (ATP III).

Achieving low-density lipoprotein cholesterol goals in high-risk patients in managed care: comparison of rosuvastatin, atorvastatin, and simvastatin in the SOLAR trial.

OBJECTIVE To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease. PATIENTS AND METHODS In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks. RESULTS A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare. CONCLUSION In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits.

Concomitant use of statins and CYP3A4 inhibitors in administrative claims and electronic medical records databases

BACKGROUND Patients may experience increased risk of adverse drug interactions when statins are administered concomitantly with cytochrome P450 3A4 (CYP3A4) inhibitors. OBJECTIVE To determine patient numbers in routine clinical practice with concomitant exposure to CYP3A4-metabolized statins and CYP3A4 inhibitors and highlight potential risk for adverse drug interaction. METHODS Exposure to prescription medications over 1 year (2005-2006) was evaluated from patient records: US PharMetrics Integrated Patient-Centric administrative claims database and the US General Electric Medical System (GEMS) database. Rates of concomitant prescribing of statins with CYP3A4 inhibitors (listed in United States of America product labels and all identified potential inhibitors) were examined in the cohort overall, in those aged ≥65 years, and in those receiving higher doses of statins. RESULTS Overall, 951,166 patient records were included (PharMetrics n = 650,825; GEMS, n = 300,341). Of these, 792,081 (83%) patients used a CYP3A4-metabolized statin as opposed to a non-CYP3A4-metabolized statin (17%). Findings from both databases were consistent. Overall, 25-30% of patients given a CYP3A4-metabolized statin were concomitantly exposed to a CYP3A4 inhibitor, including approximately 9% concomitantly exposed to a labeled inhibitor, findings consistent with those in patients aged ≥65 years, and patients on higher doses of statins. CONCLUSIONS Clinicians frequently co-prescribe CYP3A4-metabolized statins with CYP3A4 inhibitors. Physician education regarding the impact of these inhibitors on the metabolism of lovastatin, simvastatin, and atrovastatin is needed. Further studies are also needed to determine whether concomitant administration of a non-CYP3A4-metabolized statin (such as fluvastatin, pravastatin, or rosuvastatin) with a CYP3A4 inhibitor, may reduce adverse event rates in routine clinical practice.

Efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in the treatment of patients with hypercholesterolemia : A meta-analysis of clinical trials

Recent studies have documented the long-term impact of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on mortality and morbidity related to coronary heart disease, establishing the link between lowering cholesterol levels and reducing cardiac events. Our study was a comparative literature review and meta-analysis of the efficacy of four HMG-CoA reductase inhibitors-fluvastatin, lovastatin, pravastatin, and simvastatin-used in the treatment of patients with hypercholesterolemia. The data sources for our meta-analysis of the efficacy of these cholesterol-lowering agents were 52 randomized, double-masked clinical trials with at least 25 patients per treatment arm. The results showed all four agents to be effective in reducing blood cholesterol levels. We computed summary efficacy estimates for all published dose strengths for the four agents. Fluvastatin 20 mg/d reduced low-density lipoprotein cholesterol (LDL-C) levels by 21.0% and total cholesterol (total-C) levels by 16.4%; fluvastatin 40 mg/d reduced these levels by 23.1% and 17.7%, respectively. Lovastatin 20 mg/d reduced LDL-C levels by 24.9% and total-C levels by 17.7%; lovastatin 80 mg/d reduced these levels by 39.8% and 29.2%, respectively. Pravastatin 10 mg/d reduced LDL-C levels by 19.3% and total-C levels by 14.0%; pravastatin 80 mg/d reduced these levels by 37.7% and 28.7%, respectively. Simvastatin 2.5 mg/d reduced LDL-C levels by 22.9% and total-C levels by 15.7%; simvastatin 40 mg/d reduced these levels by 40.7% and 29.7%, respectively. The results of our meta-analysis can be used in conjunction with treatment objectives and comparative cost-effectiveness data for these agents to decide appropriate therapeutic alternatives for individual patients.

Cost effectiveness of rosuvastatin in patients at risk of cardiovascular disease based on findings from the JUPITER trial

Abstract Objective: This study assessed the long-term cost effectiveness of rosuvastatin therapy compared with placebo in reducing the incidence of major cardiovascular (CVD) events and mortality. Methods: A probabilistic Monte Carlo simulation model estimated long-term cost effectiveness of rosuvastatin therapy (20 mg daily) for the prevention of CVD mortality and morbidity. The model included three stages: (1) CVD prevention simulating the 4 years of the JUPITER trial, (2) initial CVD prevention beyond the trial, and (3) subsequent CVD event prevention. A US payer perspective was assessed reflecting direct medical costs, and up to a lifetime horizon. Sensitivity analyses tested the robustness of the model estimates. Results: For a hypothetical cohort of 100,000 patients at moderate and high risk of CVD events based on Framingham risk of ≥10%, estimated quality-adjusted life-years (QALYs) gained with rosuvastatin therapy compared with placebo was 33,480 over a lifetime horizon, and 25,380 and 9916 over 20-year and 10-year horizons, respectively. Approximately 12,073 events were avoided over the lifetime; 6,146 non-fatal MIs, 2905 non-fatal strokes, and 4030 CVD deaths avoided. Estimated incremental cost-effectiveness ratio (ICER) for cost per QALY was

Comparative effectiveness of rosuvastatin versus other statin therapies in patients at increased risk of failure to achieve low- density lipoprotein goals

7062 (lifetime),

Lipid levels and low-density lipoprotein cholesterol goal attainment in diabetic patients: rosuvastatin compared with other statins in usual care

10,743 (20-year horizon), and