Comparative evaluation of micro-leakage of two newer glass ionomer cements in primary molars immersed in three beverages: in vitro study

Introduction: The dietary habits of children expose the oral cavity to challenging environments. A durable interface between the restorative material and tooth surface is essential to ensure marginal integrity thereby contributing to the longevity of restoration. Objectives: The objective of this study was to compare the micro-leakage of two newer glass ionomer cements (SDI Riva Self Cure GIC and GC Fuji IX GP EXTRA) in primary molars immersed in sugarcane juice, chocolate milk and mango drink. Methods: The study included 60 extracted non carious upper and lower primary molars. The buccal and lingual surfaces were restored with SDI Riva Self Cure GIC and GC Fuji IX GP EXTRA respectively. The sample was divided into three groups (chocolate milk, mango drink, sugarcane juice). Each group (n=18) was further subdivided into three subgroups based on the immersion regime. Six teeth were kept as control. The teeth were immersed in Rhodamine B dye. Following this, micro-leakage was determined under 40 x stereomicroscope. Results: Both the materials showed micro leakage when immersed in the three beverages. When specimen under each group were compared, the microleakage score increased with an increase in immersion frequency. This was not statistically significant. The microleakage values for both the materials immersed in the three beverages were not significant. Conclusions: Both the materials used in this study can be conveniently used in restoration of primary molars.

Daclatasvir/peginterferon lambda-1a/ribavirin in patients with chronic HCV infection and haemophilia who are treatment naïve or prior relapsers to peginterferon alfa-2a/ribavirin.

AIM: This study explores the potential role of a novel interferon-containing regimen for treatment of patients with chronic hepatitis C (CHC) and underlying haemophilia. METHODS: This trial (NCT01741545) was an open-label, non-randomized phase 3 study, which included adult haemophiliacs with hepatitis C virus (HCV). Patients with HCV genotypes (GT)-2 or -3 were treated with Lambda-IFN/ribavirin (RBV)/daclatasvir (DCV) for 12 weeks (cohort A). Patients with HCV GT-1b or -4 were treated with Lambda-IFN/RBV/DCV for 12 weeks, followed by Lambda-IFN/RBV for an additional 12 weeks (cohort B). The primary endpoint was the proportion of patients with a sustained virologic response at post-treatment follow-up week 12 (SVR12). Clinical development of Lambda-IFN was discontinued during this trial leading to study termination before a 24-week post-treatment follow-up was obtained for all participants. RESULTS: Overall, 51 patients were treated (cohort A, n = 12; cohort B, n = 39). The proportion of patients achieving SVR12 was 92% in cohort A and 90% in cohort B. Therapy was generally well tolerated. The most common adverse events (AEs) were related to elevations in serum transaminases and/or bilirubin. Five serious AEs, four discontinuations due to AEs, and no deaths were reported. The rate of grade 3-4 bilirubin elevations was 17-18% across cohorts. CONCLUSION: Lambda-IFN/RBV/DCV treatment demonstrated a high SVR rate and was generally well tolerated with a safety profile consistent with expectations for this special patient population. This study supports use of DCV as part of a combination treatment regimen for haemophiliacs with CHC.

Peg-IFNα/ribavirin/protease inhibitor combination in hepatitis C virus associated mixed cryoglobulinemia vasculitis: results at week 24.

BACKGROUND: The standard-of-care treatment of patients with hepatitis C virus (HCV)-mixed cryoglobulinemia (MC) vasculitis includes pegylated interferon α (PegIFN)-α plus ribavirin and/or rituximab. About 30-40% of patients are non-responders or relapsers to such combination. OBJECTIVE: To analyse the safety and efficacy of Peg-IFNα/ribavirin/protease inhibitor combination in HCV-MC vasculitis. PATIENTS AND METHODS: Open-label, prospective, cohort study including 23 patients with HCV-MC vasculitis. Peg-IFNα/ribavirin was associated to telaprevir (375 mg three times daily, for 12 weeks, (n=15)) or boceprevir (800 mg three times daily, for 44 weeks, (n=8)) for 48 weeks. RESULTS: The median age was 59 (52.5-66) years, with 48.8% women. Thirteen patients (56.5%) were complete clinical responders, and 10 (43.5%) were partial responders at week 24. The virological response (ie, HCV RNA negativation) was of 69.6% at week 24 (p=0.005). The cryoglobulin level decreased from 0.44 to 0.06 g/l (p=0.0006) and the C4 level increased from 0.09 to 0.15 g/l (p=0.045). Grades 3 and 4 adverse events (mainly anaemia, neutropenia and thrombocytopenia) were observed in 10 cases (43.5%). Twenty patients (87%) received erythropoietin, 9 (39.1%) had red cell transfusion, and 2 (8.7%) had granulocyte stimulating agents. Antiviral therapy discontinuation was required in 8 (34.7%) patients for virological non-response (n=5), virological relapse (n=2) and depression (n=1). CONCLUSIONS: Peg-IFNα/ribavirin/protease inhibitor combination seems highly effective in HCV-MC. Such therapeutic regimen should be administered cautiously considering the high rate of side effects.

Thymosin alpha-1 with peginterferon alfa-2a/ribavirin for chronic hepatitis C not responsive to IFN/ribavirin: an adjuvant role?

This study was conducted to determine whether the adding thymosin alpha-1 to standard of care for re-treatment of nonresponding hepatitis C infections can improve sustained viral response (SVR) rates. Patients (n = 552) with hepatitis C infections not responding to the combination of Peginterferon alfa-2a or 2b with ribavirin (RBV)were randomized to receive peginterferon alfa-2a 180 mg/week with RBV 800-1200 mg/daily plus either thymosin alpha-1 1.6 mg SC twice weekly (n = 275) or placebo (n = 277) for 48 weeks. Eighty-eight per cent of patients had HCV genotype 1, 6.6% type 4, 2.2% type 2 and 3.6% type 3. SVR rates in the intention to treat population were similar between thymosin alpha-1 and placebo (12.7%vs 10.5%; P = 0.407). Among patients who completed all 48 weeks of therapy, the SVR rate was significantly higher in the thymosin alpha-1 group at 41.0% (34/83) compared with 26.3% (26/99) in the placebo group (P = 0.048). No significant difference was observed between treatment groups in the incidence of adverse events. The addition of thymosin alpha-1 to the standard of care did not increase the on-treatment HCV viral response. Thymosin alpha-1 seems to play no role in the primary therapy of the disease. This study raises the hypothesis that thymosin alpha-1 may have a secondary therapeutic role as an adjuvant in the prevention of relapses in patients achieving a virologic response during therapy.

[ANRS HC 02 RIBAVIC: histo-pathological impact]. / ANRS HC 02 RIBAVIC : impact histologique.

Anti-hepatitis C virus (HCV) therapy allows complete recovery of HCV infection (sustained virologic response). Reduction of necro-inflammation results usually in a stabilization then in a reduction of fibrosis and even of cirrhosis at least in patients with sustained virologic response. The randomised controlled RIBAVIC ANRS HC02 trial comparing the combination ribavirin-pegylated interferon-alpha2b versus ribavirine-standard interferon-alpha2b as first treatment in HIV-HCV co-infected patients allowed an analysis of 205 paired (pre- and post-treatment) biopsies using the Metavir and Ishak scores. A significant reduction was associated with sustained virologic response and non response with stabilization. There was no positive impact on fibrosis despite sustained virologic response and a deterioration in non responders. In multivariate analysis, didanosine and non response were significantly associated with fibrosis deterioration. The absence of fibrosis reversal in co-infected patients is related to virologic non response and probably to co-factors of fibrosis worsening, like the mitochondrial toxicity of antiretrovirals and especially of didanosine. In the RIBAVIC cohort (prospective followup of 383 co-infected HIV-HCV treated patients) with a median of 60 months, 21 patients (5 %) had a liver event: all were non responders and 20 had fibrosis score > or = F3. In multivariate analysis, factors associated with survival were virologic response to antiviral therapy, fibrosis score < F3 and baseline CD 4 count > 350/mL. These results emphasize the need of early therapeutic interventions to increase the rate of sustained virologic response and to decrease the rate of liver complications in the most severe patients.

Severe weight loss in HIV / HCV-coinfected patients treated with interferon plus ribavirin: incidence and risk factors.

Weight loss is reported by more than 20% of hepatitis C virus (HCV)-monoinfected patients treated with the peg-interferon (peg-IFN) and ribavirin combination. The aim of this study was to determine the incidence and risk factors of severe weight loss (> or =10%) in human immunodeficiency virus (HIV) / HCV-coinfected patients participating in a randomized, controlled 48-week trial comparing peg-IFN alpha 2b plus ribavirin with IFN alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, anti-HCV therapy and clinical and laboratory findings. One hundred eleven (28.9%) of 383 patients who received at least one dose of anti-HCV treatment subsequently had severe weight loss. Among patients who took at least 80% of the planned total dose, severe weight loss occurred in 74 patients (32.7%). In multivariate analysis, age >40 years [hazard ratio (HR), 1.59; 95% CI 1.09 to 2.31; P = 0.016], body mass index (BMI) >22 (HR, 1.72; 95% CI, 1.16 to 2.55; P = 0.0069), peg-IFN alpha-2b (HR, 1.82; 95% CI, 1.24 to 2.69; P = 0.0022) and female sex (HR, 1.60; 95% CI, 1.05 to 2.43; P = 0.027) were associated with severe weight loss. In contrast, patients taking non-nucleoside reverse transcriptase inhibitors (NNRTI)-containing antiretroviral regimens were less likely to lose weight (HR, 0.62; 95% CI, 0.39 to 0.96; P = 0.034). Lipodystrophy tended to occur more frequently in patients who had severe weight loss than in the other patients (26.1%vs 17.6%; P = 0.0682) and patients whose weight loss >5% persisted 24 weeks after the completion of anti-HCV therapy (n = 58 / 111) were more likely to be receiving stavudine-based antiretroviral therapy, suggesting that mitochondrial toxicity plays some role in weight loss. These findings show that severe weight loss is a frequent side effect of anti-HCV therapy in HIV / HCV-coinfected patients. The underlying mechanisms remain to be identified.

Thermal decomposition of commercial silicone oil to produce high yield high surface area SiC nanorods.

This article reports on the synthesis of high surface area (563m2/g) beta-SiC nanorods by thermal decomposition of commercial silicone oil at a relatively low reaction temperature (800 degrees C) in a closed Swagelok cell. High yield (75%) of SiC nanorods are obtained in this one-stage, solvent-, catalyst-, and template-free synthesis technique that runs at a relative low temperature and employs cheap single-precursor. The morphological (TEM, HR-SEM), compositional (CHNS, EDX, SAEDX]), structural (XRD, HR-TEM, and ED), thermal (TGA) characterizations and surface area analysis are carried out for the obtained SiC nanorods. The possibility of hydrogen storage in this high surface area nano-SiC rods are also tested and reported for the first time.

New treatments for chronic hepatitis C virus infection.

The treatment of hepatitis C virus infection (HCV) by a combination of pegylated interferon and ribavirin, according to early viral kinetics, leads to a sustained virological response (SVR) in more than 50% of patients with chronic infection. This SVR is a complete recovery of the infection but more than 50% of genotype 1-infected patients do not achieve SVR. A better understanding of the viral cycle, and the characterization of viral enzymes which are potential targets, resulted in the development of new molecules, direct acting antivirals (DAA) targeted against HCV, either specific of genotype 1 (protease inhibitors NS3/NS4A and polymerase inhibitors NS5B) or with a wider spectrum (NS5A or entry inhibitors), and non-specific antivirals (new interferons, cyclophilin inhibitors). We describe the results of phase II and III trials which clearly demonstrated a 20 to 30% increase in the SVR rate of genotype 1-infected patients, either naïve or treatment experienced. These new drugs should be approved by the end of 2011, after a temporary approval for compassionate use in cirrhotic patients with previous relapse or partial response to the combination therapy. In the future, the main limitations of triple therapy will be safety (cutaneous rash or anemia which may be controlled), cost, compliance, viral resistance, and drug interactions that must be avoided by educating patients and physicians.

Risk factors for anaemia in human immunodeficiency virus/hepatitis C virus-coinfected patients treated with interferon plus ribavirin.

The most frequent and the most troublesome adverse effect of interferon plus ribavirin-based therapy is anaemia. The aim of this analysis was to determine the incidence and risk factors of anaemia (Hb < 10 g/dL) in human immunodeficiency virus/hepatitis C virus (HCV)-coinfected patients receiving anti-HCV therapy. We reviewed all cases of anaemia occurring among 416 patients participating in a randomized, controlled 48-week trial comparing peginterferon (peg-IFN) alpha 2b plus ribavirin with interferon alpha-2b plus ribavirin. Univariate and multivariate analyses were used to identify links with antiretroviral treatments, HCV therapy and clinical and laboratory findings. Sixty-one (15.9%) of the 383 patients who received at least one dose of anti-HCV treatment developed anaemia. In multivariate analysis the risk of anaemia was significantly associated with zidovudine (OR, 3.27 95% CI, 1.64-6.54, P = 0.0008) and peg-IFN (OR, 2.35; 95% CI, 1.16-4.57, P = 0.0179). The risk of anaemia was lower in patients with higher baseline haemoglobin levels (OR, 0.35 95% CI, 0.26-0.49, P < 0.0001) and in patients receiving protease inhibitor-based antiretroviral therapy (OR, 0.51 95% CI, 0.30-0.86, P = 0.0114). Zidovudine discontinuation could help to avoid anaemia associated with anti-HCV therapy.

Comparison of serum hepatitis C virus (HCV) RNA and core antigen levels in patients coinfected with human immunodeficiency virus and HCV and treated with interferon plus ribavirin.

Trak-C (Ortho-Clinical Diagnostics) is an enzyme-linked immunosorbent assay-based method capable of quantifying hepatitis C virus (HCV) core antigen (CA) in serum and could be an alternative to molecular detection and quantification of HCV RNA. We have evaluated the Trak-C assay in comparison with an HCV RNA quantitative assay (Versant HCV v3.0; Bayer Diagnostics) in the follow-up of 348 treated, human immunodeficiency virus (HIV)/HCV-coinfected patients included in the ANRS HC02 RIBAVIC trial. ANRS HC02 RIBAVIC is a therapeutic, multicenter, randomized protocol comparing the efficacy of alpha interferon 2b (IFN-alpha2b) (3 million units three times a week)-ribavirin (800 mg/day) to that of pegylated IFN-alpha2b (1.5 mug/kg of body weight/week)-ribavirin (800 mg/day) during 48 weeks of treatment of HIV/HCV-coinfected patients naïve to HCV treatment. Patients were assessed for virological analysis at day 0 and weeks 4, 12, 24, 48, and 72. Correlation of HCV RNA and HCV CA at the initiation of treatment was excellent (r = 0.92). HCV RNA and CA kinetics were similar during follow-up of HCV treatment from day 0 to week 72 whatever the group of response and genotype. The positive and negative predictive values of response to the treatment at week 4 were 59 and 94%, respectively, for HCV RNA load reduction of >2 log and 54 and 94%, respectively, for HCV CA below the threshold value (4.18 log(10) pg/ml . 10(4)). Trak-C, a new assay able to quantify CA in HIV/HCV-coinfected patients, correlates well with quantitative HCV RNA assays and is cheaper and easier to perform than molecular technology. HCV CA could be a valuable alternative test for therapeutic follow-up of coinfected patients treated with IFN plus ribavirin in developing countries.