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Herbal therapies are used by more than 12% of the U.S. population each year, resulting in annual out-of-pocket expenses above $5 billion. Utilization rates are particularly high among patients with chronic diseases, and in patients frequently seen in clinic by physicians and nurse practitioners. Most physicians do not receive formal education regarding the safety of these therapies, and there is growing concern in the medical community about the potential risks to patients and the paucity of reliable information. Numerous adverse effects and interactions have been attributed to dietary supplements, based on variable levels of evidence ranging from historical use or anecdotes to pre-clinical research or high-quality clinical trials. Significant potential morbidity and costs have been indirectly associated with herb/supplement-drug interactions, including increased emergency room visits, outpatient clinic visits, and perioperative complications. However, most research has focused on efficacy rather than safety. Post-market surveillance is complicated by the uneven standardization of products between manufacturers, and in some cases between batches produced by the same manufacturer. To assure public safety around the use of dietary supplements within the framework of existing legislation and market realities, schema must evolve to more systematically monitor the safety of agents in the post-market environment; identify potentially dangerous supplements (and/or constituents); study the mechanism and potential hazards of these identified products; and clarify the process by which products may be considered for removal from the market. We discuss research and educational paradigms within this context which make use of existing surveillance mechanisms to more efficiently identify agents of particular concern. Specific examples are given. [ABSTRACT FROM AUTHOR]

Background and Objective: Hepatitis C virus (HCV) transmission occurs in 0.2%-10% of people after accidental needlestick exposures. However, postexposure prophylaxis is not currently recommended. We sought to determine the safety, tolerability, and acceptance of postexposure prophylaxis with peginterferon alfa-2b in healthcare workers (HCWs) exposed to blood from HCV-infected patients., Design: Open-label pilot trial of peginterferon alfa-2b for HCV postexposure prophylaxis., Setting: Two academic tertiary-referral centers., Methods: HCWs exposed to blood from HCV-infected patients were informed of the availability of postexposure prophylaxis. Persons who elected postexposure prophylaxis were given weekly doses of peginterferon alfa-2b for 4 weeks., Results: Among 2,702 HCWs identified with potential exposures to bloodborne pathogens, 213 (7.9%) were exposed to an HCV antibody-positive source. Of 51 HCWs who enrolled in the study, 44 (86%) elected to undergo postexposure prophylaxis (treated group). Seven subjects elected not to undergo postexposure prophylaxis (untreated group). No cases of HCV transmission were observed in either the treated or untreated group, and no cases occurred in the remaining 162 HCWs who did not enroll in this study. No serious adverse events related to a peginterferon alfa-2b regimen were recorded, but minor adverse events were frequent., Conclusion: In this pilot study, there was a lower than expected frequency of HCV transmission after accidental occupational exposure. Although peginterferon alfa-2b was safe, because of the lack of HCV transmission in either the treated or untreated groups there is little evidence to support routine postexposure prophylaxis against HCV in HCWs.

Purpose: Recent clinical trials have evaluated treatment strategies for chronic infection with hepatitis C virus (HCV) in patients co-infected with human immunodeficiency virus (HIV). Our objective was to use these data to examine the cost-effectiveness of treating HCV in an urban cohort of co-infected patients., Methods: A computer-based model, together with available published data, was used to estimate lifetime costs (2004 US dollars), life expectancy, and incremental cost per year of life saved (YLS) associated with 3 treatment strategies: (1) interferon-alfa and ribavirin; (2) pegylated interferon-alfa; and (3) pegylated interferon-alfa and ribavirin. The target population included treatment-eligible patients, based on an actual urban cohort of HIV-HCV co-infected subjects, with a mean age of 44 years, of whom 66% had genotype 1 HCV, 16% had cirrhosis, and 98% had CD4 cell counts >200 cells/mm3., Results: Pegylated interferon-alfa and ribavirin was consistently more effective and cost-effective than other treatment strategies, particularly in patients with non-genotype 1 HCV. For patients with CD4 counts between 200 and 500 cells/mm3, survival benefits ranged from 5 to 11 months, and incremental cost-effectiveness ratios were consistently less than $75,000 per YLS for men and women of both genotypes. Due to better treatment efficacy in non-genotype 1 HCV patients, this group experienced greater life expectancy gains and lower incremental cost-effectiveness ratios., Conclusions: Combination therapy with pegylated interferon-alfa and ribavirin for HCV in eligible co-infected patients with stable HIV disease provides substantial life-expectancy benefits and appears to be cost-effective. Overcoming barriers to HCV treatment eligibility among urban co-infected patients remains a critical priority.

HIV antiretroviral therapy (ART)-related hepatotoxicity is a significant clinical problem, resulting in severe elevations of liver enzymes and, potentially, liver failure and death. We retrospectively determined baseline clinical predictors of severe hepatotoxicity (SH; serum aminotransferases or total bilirubin >5 times and >2.5 times the upper limit of normal [ULN], respectively) among 8,851 subjects enrolled in 16 Adult AIDS Clinical Trial Group studies from October 1989 to June 1999. Subjects were divided into the following treatment categories: single nucleoside reverse transcriptase inhibitors (NRTIs), multiple NRTIs, nonnucleoside reverse transcriptase inhibitors (NNRTIs) combined with NRTIs, and the protease inhibitor (PI) indinavir (IDV) combined with NRTIs. SH occurred in 824 (9.3%) subjects, in 613 (6.92%) in the first 6 months and in another 211(2.38%) in the subsequent 6 months of study ART. Consistent with other reports, baseline elevation in serum aminotransferases was a significant risk factor for SH for all regimens. Risk factors not previously identified included concomitant hepatotoxic medications, thrombocytopenia, and renal insufficiency. Hepatitis C virus coinfection was associated with an increased risk of SH (odds ratio [OR] = 2.7; P < 0.003). In conclusion, this study identified known and previously unreported risk factors for severe hepatotoxicity that should be considered before the initiation of ART.

Serologic assays for HBV are the mainstay diagnostic tools for HBV infection. However, the advent of molecular biology-based techniques has added a new dimension to the diagnosis and treatment of patients with chronic HBV infection. Over the past decade, improvements in molecular technology, permitting detection of as few as 10 copies/mL of HBV DNA in serum have led to redefinitions of chronic HBV infection, as well as thresholds for antiviral treatment. As the sensitivity of these molecular techniques continues to improve, the challenge will be to standardize these as-says as well as define clinically significant levels of HBV replication.

Serologic assays for HBV are the mainstay diagnostic tools for HBV infection. However, the advent of molecular biology-based techniques has added a new dimension to the diagnosis and treatment of patients with chronic HBV infection. Over the past decade, improvements in molecular technology, permitting detection of as few as 10 copies/mL of HBV DNA in serum have led to redefinitions of chronic HBV infection, as well as thresholds for antiviral treatment. As the sensitivity of these molecular techniques continues to improve, the challenge will be to standardize these assays as well as define clinically significant levels of HBV replication.