Robert S. Epstein

Impact of Medication Adherence on Hospitalization Risk and Healthcare Cost

Objective:The objective of this study was to evaluate the impact of medication adherence on healthcare utilization and cost for 4 chronic conditions that are major drivers of drug spending: diabetes, hypertension, hypercholesterolemia, and congestive heart failure. Research Design:The authors conducted a retrospective cohort observation of patients who were continuously enrolled in medical and prescription benefit plans from June 1997 through May 1999. Patients were identified for disease-specific analysis based on claims for outpatient, emergency room, or inpatient services during the first 12 months of the study. Using an integrated analysis of administrative claims data, medical and drug utilization were measured during the 12-month period after patient identification. Medication adherence was defined by days’ supply of maintenance medications for each condition. Patients:The study consisted of a population-based sample of 137,277 patients under age 65. Measures:Disease-related and all-cause medical costs, drug costs, and hospitalization risk were measured. Using regression analysis, these measures were modeled at varying levels of medication adherence. Results:For diabetes and hypercholesterolemia, a high level of medication adherence was associated with lower disease-related medical costs. For these conditions, higher medication costs were more than offset by medical cost reductions, producing a net reduction in overall healthcare costs. For diabetes, hypercholesterolemia, and hypertension, cost offsets were observed for all-cause medical costs at high levels of medication adherence. For all 4 conditions, hospitalization rates were significantly lower for patients with high medication adherence. Conclusions:For some chronic conditions, increased drug utilization can provide a net economic return when it is driven by improved adherence with guidelines-based therapy.

Pre-Existing Fractures and Bone Mass Predict Vertebral Fracture Incidence in Women

OBJECTIVE To determine the independent contributions of bone mass and existing fractures as predictors of the risk for new vertebral fractures. SUBJECTS Postmenopausal Japanese-American women. MEASUREMENTS Baseline measurements of the distal radius, the proximal radius, and the calcaneus were obtained in 1981 using single-photon absorptiometry. Measurements of the lumbar spine were obtained in 1984 using dual-photon absorptiometry. Prevalent vertebral fractures were identified using dimensions measured on lateral radiographs; vertebral height values more than 3 SD below vertebra-specific means were considered to indicate fracture. Statistical models were used to evaluate the utility of bone mass and existing (prevalent) fractures to predict the risk for new fractures during an average follow-up of 4.7 years. MAIN RESULTS Differences of 2 SD in bone mass were associated with fourfold to sixfold increases in the risk for new vertebral fractures. A single fracture at the baseline examination increased the risk for new vertebral fractures fivefold. Presence of two or more fractures at baseline increased the risk 12-fold. A combination of low bone mass (below the 33d percentile) and the presence of two or more prevalent fractures increased the risk 75-fold, relative to women with the highest bone mass (above the 67th percentile) and no prevalent fractures. Stature, body mass index, arm span, and spinal conditions such as scoliosis, osteoarthritis, and sacroiliitis did not predict fracture incidence (P greater than 0.05). Weight was marginally predictive (P = 0.04) of fracture incidence but became nonpredictive after adjusting for bone mass (P greater than or equal to 0.05). CONCLUSIONS Both bone mass and prevalent vertebral fractures are powerful predictors of the risk for new vertebral fractures. Combining information about bone mass and prevalent fracture appears to be better for predicting new fractures than either variable alone. Physicians can use these risk factors to identify patients at greatest risk for new fractures.

Warfarin Genotyping Reduces Hospitalization Rates Results From the MM-WES (Medco-Mayo Warfarin Effectiveness Study)

OBJECTIVES This study was designed to determine whether genotype testing for patients initiating warfarin treatment will reduce the incidence of hospitalizations, including those due to bleeding or thromboembolism. BACKGROUND Genotypic variations in CYP2C9 and VKORC1 have been shown to predict warfarin dosing, but no large-scale studies have prospectively evaluated the clinical effectiveness of genotyping in naturalistic settings across the U.S. METHODS This national, prospective, comparative effectiveness study compared the 6-month incidence of hospitalization in patients receiving warfarin genotyping (n = 896) versus a matched historical control group (n = 2,688). To evaluate for temporal changes in the outcomes of warfarin treatment, a secondary analysis compared outcomes for 2 external control groups drawn from the same 2 time periods. RESULTS Compared with the historical control group, the genotyped cohort had 31% fewer hospitalizations overall (adjusted hazard ratio [HR]: 0.69, 95% confidence interval [CI]: 0.58 to 0.82, p < 0.001) and 28% fewer hospitalizations for bleeding or thromboembolism (HR: 0.72, 95% CI: 0.53 to 0.97, p = 0.029) during the 6-month follow-up period. Findings from a per-protocol analysis were even stronger: 33% lower risk of all-cause hospitalization (HR: 0.67, 95% CI: 0.55 to 0.81, p < 0.001) and 43% lower risk of hospitalization for bleeding or thromboembolism (HR: 0.57, 95% CI: 0.39 to 0.83, p = 0.003) in patients who were genotyped. During the same period, there was no difference in outcomes between the 2 external control groups. CONCLUSIONS Warfarin genotyping reduced the risk of hospitalization in outpatients initiating warfarin. (The Clinical and Economic Impact of Pharmacogenomic Testing of Warfarin Therapy in Typical Community Practice Settings [MHSMayoWarf1]; NCT00830570).

Pharmacogenomic Biomarker Information in Drug Labels Approved by the United States Food and Drug Administration: Prevalence of Related Drug Use

Study Objectives. To review the labels of United States Food and Drug Administration (FDA)‐approved drugs to identify those that contain pharmacogenomic biomarker information, and to collect prevalence information on the use of those drugs for which pharmacogenomic information is included in the drug labeling.

Trends in Medication Treatment for ADHD

Objective: This study examines demographic trends in the use of medications to treat ADHD in adult and pediatric populations. Method: Using pharmacy claims data for a large population of commercially insured Americans, the study measures ADHD treatment prevalence and drug use from 2000 to 2005. Results: In 2005, 4.4% of children (ages 0 to 19) and 0.8% of adults (ages 20 and older) used ADHD medications. Treatment rates were higher in boys (6.1%) than in girls (2.6%), but the rates for men and women were approximately equal (0.8%). During the period of the study, treatment prevalence increased rapidly (11.8% per year) for the population as a whole. Treatment rates grew more rapidly for adults than for children, more rapidly for women than for men, and more rapidly for girls than for boys. Conclusion: Improved identification of ADHD in adult and female patients has contributed to rapid growth in ADHD medication use. (J. of Att. Dis. 2007; 10(4) 335-342)

The economic cost of hip fractures in community-dwelling older adults: A prospective study

OBJECTIVES: To evaluate the incremental cost in the year after hip fracture.

Validation of a new quality of life questionnaire for benign prostatic hyperplasia

In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted.

Pain and disability associated with new vertebral fractures and other spinal conditions

Although vertebral fractures are common among older women, little is known about associations with pain and disability. In this prospective study, fractures which occurred after the initial radiograph were strong predictors of back pain and disability at the end of followup, with odds ratios (OR) of approximately 4-5. Other, independently significant predictors were self-reported history of (1) disk disease (OR = 3-9), (2) traumatic back injury (OR = 4-7), and (3) spinal arthritis (OR = 3-6). In longitudinal analyses, new fractures were associated (OR = 6.4; 95% CI = 2.6, 15.6) with increases in back pain frequency (relative to pre-fracture levels). The association with prevalent fractures was weaker, and not significant (OR = 1.7; 95% CI = 0.5, 5.6). The pain frequency index increased approximately 3-fold, relative to pre-fracture levels. At the end of followup (mean = 3.5 years), the index was still two times greater than baseline. We conclude that associations with back pain and disability are greater in magnitude for new vertebral fractures than for prevalent fractures.

Natural history of prostatism: Impact of urinary symptoms on quality of life in 2115 randomly selected community men

OBJECTIVES To assess the impact of urinary symptoms on health-related quality of life (QoL), including degree of bother, worry, interference with daily activities, psychological well-being, sexual function, and general health in a community-based cohort of men. METHODS Eligible white men (n = 2115) aged 40 to 79 years who had not undergone previous prostate surgery or had prostate cancer were randomly selected from county residents. These subjects completed a questionnaire, which asked them about frequency and bother of urinary symptoms, interference with daily activities, psychological well-being, worry about urologic disease, sexual functioning, and general health. RESULTS Men with moderate to severe voiding symptoms reported, on average, four to six times the degree of bother and interference with daily activities and twice the level of worry of men with mild symptoms. Nearly five times the degree of bother and interference was reported for those with mild than with no symptoms. A higher percentage of men with moderate to severe symptoms (26% to 33%) than mild symptoms (< 8%) reported limiting fluids before bed, travel, or driving 2 hours. Receiver operating characteristic curves support the recommended symptom index cutpoint for moderate symptoms (= 8) by differentiating men with and without bother, interference with daily living, or dissatisfaction with urinary condition. CONCLUSIONS Moderate to severe urinary symptoms have a significant impact on mens lives in terms of degree of bother, worry, interference with daily living, and psychological well-being. The recommended cutpoint on symptom index differentiates men with and without decrement in health-related quality of life.

Impact of Proton Pump Inhibitors on the Effectiveness of Clopidogrel After Coronary Stent Placement: The Clopidogrel Medco Outcomes Study

Study Objective. To investigate the potential impact of proton pump inhibitors (PPIs) on the effectiveness of clopidogrel in preventing recurrent ischemic events after percutaneous coronary intervention (PCI) with stent placement.