52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120

Inhibitory role of peroxisome proliferator-activated receptor gamma in hepatocarcinogenesis in mice and in vitro

Although peroxisome proliferator-activated receptor gamma (PPARγ) agonist have been shown to inhibit hepatocellular carcinoma (HCC) development, the role of PPARγ in hepatocarcinogenesis remains unclear. We investigated the therapeutic efficacy of PPAR

A Randomized Double-Blind Crossover Study of Phase-Shift Sound Therapy for Tinnitus

Objective. The purpose of this study was to compare the efficacy of the treatment of tinnitus with a phase-shifting pure tone to that of the same tone treatment without phase shifting. Study Design. A double-blind crossover randomized controlled trial. Setting. This study was conducted at the University Medical Center Groningen. Subjects and Methods. Twenty-two patients with predominantly tonal tinnitus underwent both intervention and control treatments. Each treatment consisted of three 30-minute sessions in 1 week. The control treatment was identical to the intervention treatment, except that the stimulus was a pure tone without phase shifting. Questionnaires, tinnitus loudness match, and annoyance and loudness ratings were used to measure treatment effects. Results. Pure-tone treatment and phase-shift treatment had no significant effect on tinnitus according to questionnaires (Tinnitus Handicap Index, Tinnitus Reaction Questionnaire, Hospital Anxiety and Depression Scale, and Maastricht Questionnaire), audiological matching procedures, and loudness and annoyance ratings of tinnitus. Furthermore, phase-shift treatment showed no additional significant improvement in comparison with pure-tone treatment. Changes in questionnaire scores due to pure-tone and the phase-shift treatment were correlated. Conclusion. On average across the group, both treatments failed to demonstrate a significant effect. Both treatments were beneficial for some patients. However, a positive effect was not demonstrated that could be attributed to the periodic shifting of the phase of the stimulus tone

Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects

Background: Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy. Methods: Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment. Results: Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% (P<0.001), more pronounced in women with baseline MPD ⩾20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed. Conclusion: Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes

Prenatal muscle development in a mouse model for the secondary dystroglycanopathies

The defective glycosylation of α-dystroglycan is associated with a group of muscular dystrophies that are collectively referred to as the secondary dystroglycanopathies. Mutations in the gene encoding fukutin-related protein (FKRP) are one of the most common causes of secondary dystroglycanopathy in the UK and are associated with a wide spectrum of disease. Whilst central nervous system involvement has a prenatal onset, no studies have addressed prenatal muscle development in any of the mouse models for this group of diseases. In view of the pivotal role of α-dystroglycan in early basement membrane formation, we sought to determine if the muscle formation was altered in a mouse model of FKRP-related dystrophy

Novel methodology for predicting the critical salt concentration of bubble coalescence inhibition

Bubble coalescence in some salt solutions can be inhibited if the salt concentration reaches a critical concentration Ccr. There are three models available for Ccr in the literature, but they fail to predict Ccr correctly. The first two models employ the van der Waals attraction power laws to establish Ccr from the discriminant of quadratic or cubic polynomials. To improve the two models, the third model uses the same momentum balance equation of the previous models but different intermolecular force generated by water hydration with exponential decaying. The third prediction for Ccr requires the experimental input for film rupture thickness and is incomplete. We show further in this paper that the third model is incorrect. We propose a novel methodology for determining C cr which resolves the mathematical uncertainties in modeling C cr and can explicitly predict it from any relevant intermolecular forces. The methodology is based on the discovery that Ccr occurs at the local maximum of the balance equation for the capillary pressure, disjoining pressure, and pressure of the Gibbs-Marangoni stress. The novel generic approach is successfully validated using nonlinear equations for complicated disjoining pressure

Minority youth, crime, conflict, and belonging in Australia

In recent decades, the size and diversity of the minority population of contemporary western societies has increased significantly. To the critics of immigration, minority youth have been increasingly linked to crime, criminal gangs, anti-social behaviour, and riots. In this article, we draw on fieldwork conducted in Sydney, Australia's largest and most ethnically diverse city, to probe aspects of the criminality, anti-social behaviour, national identity, and belonging of ethnic minority youth in Australia. We conclude that the evidence on minority youth criminality is weak and that the panic about immigrant youth crime and immigrant youth gangs is disproportionate to the reality, drawing on and in turn creating racist stereotypes, particularly with youth of 'Middle Eastern appearance'. A review of the events leading up to the Sydney Cronulla Beach riots of December 2005 suggests that the underlying cause of the riots were many years of international, national, and local anti-Arab, anti-Muslim media discourse, and political opportunism, embedded in changing but persistent racist attitudes and practises. Our argument is that such inter-ethnic conflict between minority and majority youth in Sydney is the exception, not the rule. Finally, we draw on a hitherto unpublished survey of youth in Sydney to explore issues of national identity and belonging among young people of diverse ethnic and religious background. We conclude that minority youth in Sydney do not live 'parallel lives' but contradictory, inter-connected cosmopolitan lives. They are connected to family and local place, have inter-ethnic friendships but are often disconnected to the nation and the flag. © 2009 Springer Science+Business Media B.V