Snapshot on drug-resistance rate and profiles in patients with chronic hepatitis B receiving nucleos(t)ide analogues in clinical practice.

While the selection of complex HBV drug-resistance patterns on therapeutic failure can compromise the efficacy of anti-HBV therapies, recent data show that patients failing treatment without drug-resistance have a rate of virological success close to drug-naive patients. The goal of this study is defining, in clinical practice, the burden of drug-resistance mutations in a cohort of patients treated with anti-HBV drugs. Prevalence and patterns of drug-resistance were analyzed by RT-sequencing in 204 patients infected chronically: 148 experiencing virological rebound (defined as an increase in serum HBV-DNA > 20 IU/ml after achieving virological success [HBV-DNA < 20 IU/ml]), and 56 null/partial responders (always detectable serum HBV-DNA [>20 IU/ml] within 48 weeks of therapy). The highest rate of drug-resistance was observed in patients experiencing virological rebound (prevalence, 79.1%). Conversely, almost half (46.4%) null/partial responders have no evidence of drug-resistance. The rate of drug-resistance was higher in patients treated with lamivudine (76.8% [109/142]) and telbivudine (83.3% [5/6]), followed by adefovir (62.5% [15/24]), and entecavir (52.2% [12/23]). Complex mutational patterns characterized by the co-presence of rtM204V/I-rtA181T/V (impairing the efficacy of all anti-HBV drugs) were detected in four patients (2.7%) with virological rebound. Drug-resistance is the main cause of failure to therapy in patients experiencing virological rebound, supporting the need of rapid switch to anti-HBV drugs with higher genetic barrier and potency (entecavir/tenofovir). Conversely, nearly half of null/partial responders shows no evidence of drug-resistance mutations, maintaining high chance of achieving therapeutic success with the same class of drug. In this setting, genotypic resistance may help in selecting patients still carrying wild-type viruses, that may take major benefits from antiviral treatment.

The impact of socioeconomic level on influenza vaccination among Italian adults and elderly: a cross-sectional study.

OBJECTIVE: To assess the predictive factors of influenza vaccination among Italian adults, focusing on socioeconomic differences. METHODS: A cross-sectional study was carried out using interview and self-reported data on 102,095 subjects aged 25-89 years from the national survey "health conditions and health care services use" conducted in Italy in 1999-2000. Analyses were stratified by age and multiple logistic regression models were used to estimate odds ratios (OR) of influenza vaccination. RESULTS: Approximately one in six individuals (17.3%) received an influenza vaccine in the previous 12 months. Older age, poor health status and former smoking were all positively associated with influenza vaccination (P-value<0.05). Lower educated individuals and subjects with manual occupations were less likely to be vaccinated than those better off, with an OR ranging from 0.65 (95% CI 0.55, 0.77) to 0.82 (95% CI 0.71, 0.93). Among individuals aged 65-89 there was no apparent influence of both variables on the likelihood of receiving the influenza vaccine. CONCLUSIONS: Socioeconomic inequalities in influenza vaccine uptake were present among the adults but not among the elderly. Because in Italy the National Health Service provides influenza vaccination to the elderly free of charge, it is possible that this policy attenuated the socioeconomic differential.

Toxicological profile of hydrofluoropolyethers.

Hydrofluoropolyethers (HFPE) are a family of linear oligomeric fluorinated fluids comprising a chain of difluoromethoxy and tetrafluoroethoxy repeating units with terminal OCF2H end groups, each of which contains an isolated hydrogen atom. These fluids have been designed as low environmental impact substitutes for perfluorinated organic substances in a number of applications including heat transfer and fire suppression agents, and as a solvent. The toxicological profile of these new fluids has been evaluated and is presented in this paper. Acute toxicity tests have been performed on Sprague-Dawley Crl: CD (SD) BR rats using oral, dermal, and inhalation routes. No deaths were recorded even at the highest tested concentrations, and the resultant LD50/LC50 values were >5000 mg/kg (oral), >2000 mg/kg (dermal), and >26,411 ppm (inhalation: reversible anaesthetic effects, e.g., lethargy, seen at this exposure concentration). Other short-term tests (skin and eye irritation, skin sensitisation, genotoxicity tests in vitro and in vivo, cardiac sensitisation) were also performed, and no hazardous properties were identified. Effects of repeated exposure by inhalation were examined in rats over test periods of 5, 14, 28, and 90 days. Effects on embryo-foetal development in the rat have also been studied. The 28-day, 90-day and developmental studies were performed using nominal HFPE concentrations of 1000, 3300, and 10,000 ppm (6h/day: actual exposures confirmed by test atmosphere analysis), and the highest tested concentration proved to be an NOAEL in each study. Major observed effects were elevated urinary (inorganic) fluoride levels and increased liver weights with centrilobular hepatocyte hypertrophy (considered an adaptive response, linked to hepatic metabolism of absorbed material).

Three phase emulsions for controlled delivery in the cosmetic field.

Synopsis Adding perfluoropolymethylisopropylether (Fomblin HC) to conventional cosmetic emulsion, causes the physicochemical and applicative properties of the formulation to be deeply modified, the main feature being the formation of three phase systems. The in vitro effects on percutaneous absorption of adding Fomblin HC to a cosmetic emulsion of three model compounds was assessed using caffeine, testosterone and tritiated water as model compounds. In vitro experiments were carried out through human skin using static and flow-through diffusion cells. The presence of Fomblin HC (1, 3, 5%) in the emulsion decreased the percutaneous absorption of testosterone (0.01%) but increased water permeation. These effects were dependent on Fomblin HC concentration. On the contrary, caffeine flux through the skin was not affected by Fomblin addition to the emulsion.