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Context The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease, despite scant and conflicting evidence of its efficacy. Objective To determine the effect of silymarin on liver disease activity in patients with chronic hepatitis C virus (HCV) infection unsuccessfully treated with interferon-based therapy. Design, Setting, and Participants Multicenter, double-blind, placebo-controlled trial conducted at 4 medical centers in the United States. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (ALT) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Enrollment began in May 2008 and was completed in May 2010, with the last follow-up visit completed in March 2011. Intervention Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks. Main Outcome Measures The primary outcome measure was serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50% decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures. Results After 24 weeks of treatment, only 2 participants in each treatment group (P ≥ .99) met the primary outcome measure (3.8% [95% CI, 0.5% to 13.2%] for placebo, 4.0% [95% CI, 0.5% to 13.7%] for 420-mg silymarin, and 3.8% [95% CI, 0.5% to 13.2%] for 700-mg silymarin). The mean decline in serum ALT activity at the end of treatment did not differ significantly (P = .75) across the 3 treatment groups (mean decline, −4.3 [95% CI, −17.3 to 8.7] U/L for placebo, −14.4 [95% CI, −41.6 to 12.7] U/L for 420-mg silymarin, −11.3 [95% CI, −27.9 to 5.4] U/L for 700-mg silymarin); there likewise were no significant differences in HCV RNA levels (mean change, 0.07 [95% CI, −0.05 to 0.18] log 10 IU/mL for placebo, −0.03 [95% CI, −0.18 to 0.12] log 10 IU/mL for 420-mg silymarin, 0.04 [95% CI, −0.08 to 0.16] log 10 IU/mL for 700-mg silymarin; P = .54) or quality-of-life measures. The adverse event profile of silymarin was comparable with that of placebo. Conclusion Higher than customary doses of silymarin did not significantly reduce serum ALT levels more than placebo in participants with chronic HCV infection unsuccessfully treated with interferon-based therapy. Trial Registration clinicaltrials.gov Identifier: NCT00680342

Background: There has been a recent resurgence of severe infections with Streptococcus pyogenes , including bacteremias and a toxic shock—like syndrome. The purpose of this study was to examine the influence of intravenous drug use on the incidence, clinical epidemiology, and severity of S pyogenes bacteremia. Methods: We conducted a retrospective survey of medical records at a 500-bed tertiary care urban hospital and at a nearby 500-bed suburban university-affiliated hospital. All patients from each hospital with documented S pyogenes bacteremia from January 1, 1979, to December 31, 1989, were included. We examined demographic and clinical data from cases at the two institutions, serologic findings from a subset of isolates from the urban hospital, and factors associated with mortality from S pyogenes bacteremia by stepwise logistic regression analysis. Results: Ninety-five cases of S pyogenes bacteremia were identified, with 65% (62 cases) occurring at the urban center. Intravenous drug use occurred more frequently at the urban center ( P P =.001). Infection with the human immunodeficiency virus occurred in a subset of the injecting drug users at the urban center. Cellulitis and cutaneous abscesses were the most common sources of bacteremia at both centers. During the study period, the numbers of S pyogenes bacteremias increased at the urban center ( P =.007), accompanied by a significant increase in the proportion of infections associated with parenteral drug use ( P =.003). There was no change in the prevalence of any T type throughout the study period and no clustering of T types among injecting drug users. The overall mortality was 23% (20/89). By logistic regression analysis, age older than 65 years (relative risk [RR], 14; 95% confidence interval [CI], 3.2 to 68) and the presence of the toxic shock— like syndrome (RR, 36; 95% CI, 2.2 to 600) were significantly associated with mortality due to S pyogenes bacteremia. Conclusions: Intravenous drug use accounted for an increase in cases of S pyogenes bacteremia at an innercity hospital. However, advanced age and the toxic shock—like syndrome were the most important predictors of mortality. (Arch Intern Med. 1993;153:2679-2684)

• Since nationwide surveillance for pneumococcal bacteremia in the United States is not done, community-based studies are useful alternative methods to monitor trends in this disease. Data on the incidence of pneumococcal bacteremia in Charleston County, South Carolina, from 1974 to 1976, have been used to support cost-effective pneumococcal vaccine programs for the elderly. We reevaluated the incidence of pneumococcal bacteremia in Charleston County in 1986 and 1987 to assess whether earlier estimates remained valid given changes in medical practice. During 1986 and 1987, overall annual incidence of pneumococcal bacteremia in Charleston County was 18.7 per 100 000 (95% confidence limits, 13.7 to 23.6 per 100 000), which represents a 2.3-fold increase over the earlier rate. The increase coincided with a 2.2-fold increase in the annual number of blood cultures processed at four Charleston County hospital laboratories from 1975 to 1987 despite only a 1.1-fold increase in the number of patients discharged from these hospitals. Annualized rates increased 2.3-fold for adults more than or equal to 65 years old to 53 per 100 000 and 4.6-fold for children less than 2 years old to 162 per 100 000. The case-fatality rate of bacteremic patients was 18%, compared with 21% in the earlier study. The casefatality rate for more than or equal to 65 years of age was 44%. Ninety-one percent of adults 19 to 64 years old with bacteremia had underlying medical conditions for which pneumococcal vaccine is recommended; all persons 55 to 64 years old had at least one underlying condition. The marked increases in pneumococcal bacteremia rates detected are likely due to more routine culturing of blood from symptomatic patients with pneumococcal disease. These findings emphasize the need for effective programs promoting use of pneumococcal vaccine in high-risk groups, particularly those more than or equal to 65 years old, and the development of a more immunogenic vaccine for children less than 2 years old. ( Arch Intern Med. 1990;150:1401-1405)