The effect of medication adherence on health care utilization in bipolar disorder.

A retrospective analysis of electronic prescription and medical claims representing approximately 1.4 million managed care commercial health plan members with mental health benefits was conducted. The effect of patient adherence to traditional mood-stabilizer therapy (lithium, valproate, carbamazepine, lamotrigine, or oxcarbazepine) for bipolar disorder on mental health-related hospitalization was assessed among 1,399 patients (mean age, 42.9 yr; 66.3% female) studied. Reduced adherence to traditional mood-stabilizing therapy (< 80%) in patients with bipolar disorder was associated with significantly greater risk of mental health-related, emergency room visits (odds ratio, 1.98; 95% confidence interval, 1.38-2.84) and inpatient hospitalizations (odds ratio, 1.71; 95% confidence interval, 1.27-2.32), even after adjusting for age, gender, and comorbidity.

Treatment patterns and real-world effectiveness of warfarin in nonvalvular atrial fibrillation within a managed care system.

OBJECTIVE: To examine warfarin utilization and clinical effectiveness among patients with nonvalvular atrial fibrillation within usual clinical care in a managed care system. RESEARCH DESIGN AND METHODS: A retrospective analysis of health care claims for an approximately four million member managed care organization was performed. Health plan members with a diagnosis of nonvalvular atrial fibrillation in calendar year 2000 were identified and stratified into two cohorts: Warfarin Therapy (newly initiating warfarin) or Warfarin Candidates (eligible for warfarin therapy according to the ACC/AHA/ESC Guidelines for the Management of Patients with Atrial Fibrillation, but did not receive warfarin). MEASUREMENTS: The occurrence of thromboembolism, ischemic stroke, and hemorrhage during a maximum 720-day follow-up were compared between cohorts, adjusting for age, gender, and other risk factors, using Cox regression. RESULTS: Among 12 539 subjects (mean age 78.0 +/- 8.8 years) with nonvalvular atrial fibrillation, 4895 (39.0%) initiated Warfarin Therapy and 7644 (61.0%) were Warfarin Candidates. Event occurrences among Warfarin Therapy vs. Warfarin Candidates were: ischemic stroke, 3.7% vs. 4.5%; any thromboembolism, 7.8% vs. 10.8%; and hemorrhage, 4.4% vs. 4.9%, respectively. Warfarin therapy was not associated with an increased risk for hemorrhage (hazard ratio [HR] = 0.97, 95% confidence interval [CI] = 0.82-1.15), while risks for ischemic stroke and any thromboembolism were significantly reduced, by 22% (HR = 0.78, 95% CI = 0.65-0.93) and 34% (HR = 0.66, 95% CI = 0.59-0.75), respectively. CONCLUSIONS: Within usual clinical care for the managed care population examined, warfarin remains underused despite current guidelines recommending its use in nearly all patients with nonvalvular atrial fibrillation. Although utilization of anticoagulation clinics and INR values attained were unknown in this study, the observed risk reductions for ischemic stroke and thromboembolism were lower than those achieved in clinical trials, while no increased risk for hemorrhage was observed. These findings suggest that warfarin is used conservatively, and dosed cautiously, diminishing the full potential benefit of anticoagulant therapy in patients with nonvalvular atrial fibrillation.

The Pharmacokinetics and Pharmacodynamics of Methylprednisolone in Chronic Renal Failure.

Methylprednisolone (MP) pharmacokinetics and its directly suppressive effects on cortisol secretion, circulating T-cells, and basophils in blood were compared in six chronic renal failure (CRF) subjects and six healthy controls after an IV administration of MP 0.6 mg kg(minus sign1) as the sodium succinate ester. The CRF subjects were studied between hemodialysis treatments. The total clearance of methylprednisolone sodium succinate (the prodrug) was reduced by 40% in CRF; however, the pharmacokinetics of methylprednisolone remained unchanged. Methylprednisolone clearance was approximately 280 ml h(minus sign1) kg(minus sign1) and volume of distribution was about 1.1 L kg(minus sign1). Physiological pharmacodynamic models were applied for the immediate effects of MP, based on the premise that receptor binding is followed by rapid suppression of the secretion of cortisol and recirculation of basophils, T-helper cells, and T-suppressor cells, which persist until inhibitory concentrations (IC(50)) of methylprednisolone disappear. The difference in IC(50) for each pharmacodynamic parameter was not statistically significant, suggesting no difference in the responsiveness of these factors to methylprednisolone in CRF. As the pharmacokinetics of other corticosteroids are altered in CRF, the lack of pharmacokinetic and pharmacodynamic changes of methylprednisolone may engender a therapeutic advantage for this corticosteroid in CRF.