Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or IIb hypercholesterolemia.

This randomized, double-blind, placebo-controlled trial was conducted in 52 centers in North America to compare the effects of the new, highly effective statin, rosuvastatin, with atorvastatin and placebo in hypercholesterolemic patients. After a 6-week dietary run-in, 516 patients with low-density lipoprotein (LDL) cholesterol > or =4.14 mmol/L (160 mg/dl) and < 6.47 mmol/L (250 mg/dl) and triglycerides < or =4.52 mmol/L (400 mg/dl) were randomized to 12 weeks of once-daily placebo (n = 132), rosuvastatin 5 mg (n = 128), rosuvastatin 10 mg (n = 129), or atorvastatin 10 mg (n = 127). The primary efficacy end point was percent change in LDL cholesterol. Secondary efficacy variables were achievement of National Cholesterol Education Program (NCEP) Adult Treatment Panel II (ATP II), ATP III, and European Atherosclerosis Society LDL cholesterol goals and percent change from baseline in high-density lipoprotein (HDL) cholesterol, total cholesterol, triglycerides, non-HDL cholesterol, apolipoprotein B, and apolipoprotein A-I. Rosuvastatin 5 and 10 mg compared with atorvastatin 10 mg were associated with greater LDL cholesterol reductions (-40% and -43% vs 35%; p <0.01 and p <0.001, respectively) and HDL cholesterol increases (13% and 12% vs 8%, p <0.01 and p <0.05, respectively). Total cholesterol and apolipoprotein B reductions and apolipoprotein A-I increases were also greater with rosuvastatin; triglyceride reductions were similar. Rosuvastatin 5 and 10 mg were associated with improved achievement in ATP II (84% in both rosuvastatin groups vs 73%) and ATP III (84% and 82% vs 72%) LDL cholesterol goals, and rosuvastatin 10 mg was more effective than atorvastatin in achieving European Atherosclerosis Society LDL cholesterol goals. Both treatments were well tolerated.     

Measurement of Phenotype and Absolute Number of Circulating Heparin-Binding Hemagglutinin,ESAT-6 and CFP-10, and Purified Protein Derivative Antigen-Specific CD4 T Cells Can Discriminate Active from Latent Tuberculosis Infection

The tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are used as adjunctive tests for the evaluation of suspected cases of active tuberculosis (TB). However, a positive test does not differentiate latent from active TB. We investigated whether flow cytometric measurement of novel combinations of intracellular cytokines and surface makers on CD4 T cells could differentiate between active and latent TB after stimulation with Mycobacterium tuberculosis-specific proteins. Blood samples from 60 patients referred to the Singapore Tuberculosis Control Unit for evaluation for active TB or as TB contacts were stimulated with purified protein derivative (PPD), ESAT-6 and CFP-10, or heparin-binding hemagglutinin (HBHA). The CD4 T cell cytokine response (IFN-γ, interleukin-2 [IL-2], interleukin-17A [IL-17A], interleukin-22 [IL-22], granulocyte-macrophage colony-stimulating factor [GM-CSF], and tumor necrosis factor alpha [TNF-α]) and surface marker expression (CD27, CXCR3, and CD154) were then measured. We found that the proportion of PPD-specific CD4 T cells, defined as CD154⁺ TNF-α⁺ cells that were negative for CD27 and positive for GM-CSF, gave the strongest discrimination between subjects with latent and those with active TB (area under the receiver operator characteristic [ROC] curve of 0.9277; P < 0.0001). Also, the proportions and absolute numbers of HBHA-specific CD4 T cells were significantly higher in those with latent TB infection, particularly CD154⁺ TNF-α⁺ IFN-γ⁺ IL-2⁺ and CD154⁺ TNF-α⁺ CXCR3⁺. Finally, we found that the ratio of ESAT-6- and CFP-10-responding to HBHA-responding CD4 T cells was significantly different between the two study populations. In conclusion, we found novel markers of M. tuberculosis-specific CD4 cells which differentiate between active and latent TB.     

Attendance at specialist hepatitis clinics and initiation of antiviral treatment among persons chronically infected with hepatitis C: examining the early impact of Scotland's Hepatitis C Action Plan

Primary goals of the Hepatitis C Action Plan for Scotland Phase II (May 2008–March 2011) were to increase, among persons chronically infected with the hepatitis C (HCV) virus, attendance at specialist outpatient clinics and initiation on antiviral therapy. We evaluated progress towards these goals by comparing the odds, across time, of (a) first clinic attendance within 12 months of HCV diagnosis (n = 9747) and (b) initiation on antiviral treatment within 12 months of first attendance (n = 5736). Record linkage between the national HCV diagnosis (1996–2009) and HCV clinical (1996–2010) databases and logistic regression analyses were conducted for both outcomes. For outcome (a), 32% and 45% in the respective pre‐Phase II (before 1 May 2008) and Phase II periods attended a specialist clinic within 12 months of diagnosis; the odds of attendance within 12 months increased over time (OR = 1.05 per year, 95% CI: 1.04–1.07), but was not significantly greater for persons diagnosed with HCV in the Phase II era, compared with the pre‐Phase II era (OR = 1.1, 95% CI: 0.9–1.3), after adjustment for temporal trend. For outcome (b), 13% and 28% were initiated on treatment within 12 months of their first clinic attendance in the pre‐Phase II and Phase II periods, respectively. Higher odds of treatment initiation were associated with first clinic attendance in the Phase II (OR = 1.9, 95% CI: 1.5–2.4), compared with the pre‐Phase II era. Results were consistent with a positive impact of the Hepatitis C Action Plan on the treatment of chronically infected individuals, but further monitoring is required to confirm a sustained effect.     

Risk of transmission associated with sharing drug injecting paraphernalia: analysis of recent hepatitis C virus (HCV) infection using cross‐sectional survey data

Sharing injecting paraphernalia (containers, filters and water) poses a risk of transmitting the hepatitis C virus (HCV). The prevalence of, and risk of HCV from, such behaviour has not been extensively reported in Europe. People who inject drugs (PWID) were recruited in cross‐sectional surveys from services providing sterile injecting equipment across Scotland between 2008 and 2010. Participants completed a questionnaire and provided a blood spot for anonymous testing. Logistic regression was used to examine the association between recent HCV infection (anti‐HCV negative and HCV‐RNA positive) and self‐reported measures of injecting equipment sharing in the 6 months preceding interview. Twelve per cent of the sample reported sharing needles/syringes, and 40% reported sharing paraphernalia in the previous 6 months. The adjusted odds ratios (AOR) for sharing needles/syringes (+/− paraphernalia), and sharing only paraphernalia in the last 6 months were 6.7 (95% CI 2.6–17.1) and 3.0 (95% CI 1.2–7.5), respectively. Among those who reported not sharing needles/syringes, sharing containers and filters were both significantly associated with recent HCV infection (AOR 3.1, 95% CI 1.3–7.8 and 3.1, 95% CI 1.3–7.5, respectively); sharing water was not. We present the first study to apply a cross‐sectional approach to the analysis of the association between sharing paraphernalia and incident HCV infection and demonstrate consistent results with previous longitudinal studies. The prevalence of paraphernalia sharing in our study population is high, representing significant potential for HCV transmission.