Enhancing Pharmacovigilance from the US Experience: Current Practices and Future Opportunities.

This review is intended to present perspectives from the US experience in enhancing pharmacovigilance on current practices and future opportunities. Best practices concepts could be applied worldwide through the presentation of how three pillars of pharmacovigilance: (1) medical and scientific excellence, (2) operational and compliance excellence, and (3) knowledge sharing and experts development in the field could serve as a framework for the establishment of an efficient and successful global pharmacovigilance system.

Prevalence and cost of HIV-associated weight loss in a managed care population.

OBJECTIVE: To estimate the prevalence of HIV-associated weight loss among HIV patients in a US managed care population, and compare demographic and clinical characteristics of HIV patients with and without evidence of HIV-associated weight loss. RESEARCH DESIGN AND METHODS: A retrospective observational study was conducted using a large, geographically diverse US managed care population to identify commercial enrollees with HIV/AIDS from 1/1/2005-7/31/2007, based on a combination of HIV/AIDS diagnosis codes or antiretroviral treatment. HIV-associated weight loss status was defined according to an algorithm combining evidence for weight loss-associated conditions, anorexia symptoms, and various treatments for weight loss or wasting. Among HIV patients continuously enrolled in the health plan for one year, patient demographics, treatments, and comorbidities were compared between patients with and without evidence for weight loss. RESULTS: A total of 22,535 patients with HIV/AIDS were identified, including 2098 who met the criteria for weight loss (estimated prevalence 9.3%; 95% CI: 8.9% - 9.7%). Among 12,187 continuously enrolled patients with HIV, 1006 (8.3%) had evidence of HIV-associated weight loss. Patients with HIV-associated weight loss were older (44.1 vs. 42.6 years), and more men had HIV-associated weight loss than women (8.8% vs. 5.3%). A number of comorbidities were more common among patients with HIV-associated weight loss. On average, these patients also had more ambulatory (24.0 vs. 13.4), ER (1.4 vs. 0.8), and inpatient visits (0.5 vs. 0.1). Total annual health care costs for patients with HIV-associated weight loss were more than double (mean $45,686 vs. $19,960) the costs for HIV patients without weight loss. CONCLUSIONS: Despite the availability of effective antiretroviral therapy, weight loss remains a problem among patients with HIV. Based on this analysis, almost 1 in 10 managed care patients with HIV have evidence of HIV-associated weight loss. These patients tend to have more comorbidities, use more health care resources, and incur greater costs compared to patients without HIV-associated weight loss. Patients with HIV-associated weight loss were generally sicker than the non-weight loss cohort; thus, the increased costs observed in this population may not be directly or wholly attributable to HIV-associated weight loss. In addition, limitations common to analyses of administrative claims data should be considered when interpreting these results.

Role of a critical visceral adipose tissue threshold (CVATT) in metabolic syndrome: implications for controlling dietary carbohydrates: a review.

There are likely many scenarios and pathways that can lead to metabolic syndrome. This paper reviews mechanisms by which the accumulation of visceral adipose tissue (VAT) may contribute to the metabolic syndrome, and explores the paradigm of a critical VAT threshold (CVATT). Exceeding the CVATT may result in a number of metabolic disturbances such as insulin resistance to glucose uptake by cells. Metabolic profiles of patients with visceral obesity may substantially improve after only modest weight loss. This could reflect a significant reduction in the amount of VAT relative to peripheral or subcutaneous fat depots, thereby maintaining VAT below the CVATT. The CVATT may be unique for each individual. This may help explain the phenomena of apparently lean individuals with metabolic syndrome, the so-called metabolically normal weight (MONW), as well as the obese with normal metabolic profiles, i.e., metabolically normal obese (MNO), and those who are "fit and fat." The concept of CVATT may have implications for prevention and treatment of metabolic syndrome, which may include controlling dietary carbohydrates. The identification of the CVATT is admittedly difficult and its anatomical boundaries are not well-defined. Thus, the CVATT will continue to be a work in progress.

Inflammation and its relationship to insulin resistance, type 2 diabetes mellitus, and endothelial dysfunction.

In the past decade, clinical, laboratory, and epidemiological research have coalesced to give rise to a new paradigm for understanding type 2 diabetes mellitus (DM). In this review, we present data that DM has an inflammatory etiology and that inflammation plays a role in diabetic complications, especially cardiovascular disease. This new paradigm offers insight into the relationship between DM and obesity. It also suggests possible new avenues of treatment.