52 research outputs found
Boceprevir for untreated chronic HCV genotype 1 infection.
International audienceBACKGROUND: Peginterferon-ribavirin therapy is the current standard of care for chronic infection with hepatitis C virus (HCV). The rate of sustained virologic response has been below 50% in cases of HCV genotype 1 infection. Boceprevir, a potent oral HCV-protease inhibitor, has been evaluated as an additional treatment in phase 1 and phase 2 studies. METHODS: We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were randomly assigned to one of three groups. In all three groups, peginterferon alfa-2b and ribavirin were administered for 4 weeks (the lead-in period). Subsequently, group 1 (the control group) received placebo plus peginterferon-ribavirin for 44 weeks; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks, and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks. Nonblack patients and black patients were enrolled and analyzed separately. RESULTS: A total of 938 nonblack and 159 black patients were treated. In the nonblack cohort, a sustained virologic response was achieved in 125 of the 311 patients (40%) in group 1, in 211 of the 316 patients (67%) in group 2 (P<0.001), and in 213 of the 311 patients (68%) in group 3 (P<0.001). In the black cohort, a sustained virologic response was achieved in 12 of the 52 patients (23%) in group 1, in 22 of the 52 patients (42%) in group 2 (P=0.04), and in 29 of the 55 patients (53%) in group 3 (P=0.004). In group 2, a total of 44% of patients received peginterferon-ribavirin for 28 weeks. Anemia led to dose reductions in 13% of controls and 21% of boceprevir recipients, with discontinuations in 1% and 2%, respectively. CONCLUSIONS: The addition of boceprevir to standard therapy with peginterferon-ribavirin, as compared with standard therapy alone, significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection. The rates were similar with 24 weeks and 44 weeks of boceprevir
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Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1): an open-label, randomised, multicentre phase 2 trial
Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin.
In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 ÎŒg/kg plus ribavirin 800â1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400â1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with
ClinicalTrials.gov, number
NCT00423670.
Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54%, 95% CI 44â64], p=0·013 for PRB28; 58/103 [56%, 44â66], p=0·005 for PR4/PRB24; 69/103 [67%, 57â76], p<0·0001 for PRB48; and 77/103 [75%, 65â83], p<0·0001 for PR4/PRB44;
vs 39/104 [38%, 28â48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27%]), and a rate of relapse (six of 27 [22%]) similar to control (12/51 [24%]). Boceprevir-based groups had higher rates of anaemia (227/416 [55%]
vs 35/104 [34%]) and dysgeusia (111/416 [27%]
vs nine of 104 [9%]) than did the control group.
In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone.
Merck
Aerodynamic investigations of ventilated brake discs.
The heat dissipation and performance of a ventilated brake disc strongly depends
on the aerodynamic characteristics of the flow through the rotor passages. The
aim of this investigation was to provide an improved understanding of ventilated
brake rotor flow phenomena, with a view to improving heat dissipation, as well
as providing a measurement data set for validation of computational fluid
dynamics methods. The flow fields at the exit of four different brake rotor
geometries, rotated in free air, were measured using a five-hole pressure probe
and a hot-wire anemometry system. The principal measurements were taken using
two-component hot-wire techniques and were used to determine mean and unsteady
flow characteristics at the exit of the brake rotors. Using phase-locked data
processing, it was possible to reveal the spatial and temporal flow variation
within individual rotor passages. The effects of disc geometry and rotational
speed on the mean flow, passage turbulence intensity, and mass flow were
determined. The rotor exit jet and wake flow were clearly observed as
characterized by the passage geometry as well as definite regions of high and
low turbulence. The aerodynamic flow characteristics were found to be reasonably
independent of rotational speed but highly dependent upon rotor geometry
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Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection
Background
Treatment guidelines recommend the use of peginterferon alfa-2b or peginterferon alfa-2a in combination with ribavirin for chronic hepatitis C virus (HCV) infection. However, these regimens have not been adequately compared.
Methods
At 118 sites, patients who had HCV genotype 1 infection and who had not previously been treated were randomly assigned to undergo 48 weeks of treatment with one of three regimens: peginterferon alfa-2b at a standard dose of 1.5 ÎŒg per kilogram of body weight per week or a low dose of 1.0 ÎŒg per kilogram per week, plus ribavirin at a dose of 800 to 1400 mg per day, or peginterferon alfa-2a at a dose of 180 ÎŒg per week plus ribavirin at a dose of 1000 to 1200 mg per day. We compared the rate of sustained virologic response and the safety and adverse-event profiles between the peginterferon alfa-2b regimens and between the standard-dose peginterferon alfa- 2b regimen and the peginterferon alfa-2a regimen.
Results
Among 3070 patients, rates of sustained virologic response were similar among the regimens: 39.8% with standard-dose peginterferon alfa-2b, 38.0% with low-dose peginterferon alfa-2b, and 40.9% with peginterferon alfa-2a (P=0.20 for standarddose vs. low-dose peginterferon alfa-2b; P=0.57 for standard-dose peginterferon alfa-2b vs. peginterferon alfa-2a). Estimated differences in response rates were 1.8% (95% confidence interval [CI], â2.3 to 6.0) between standard-dose and low-dose peginterferon alfa-2b and â1.1% (95% CI, â5.3 to 3.0) between standard-dose peginterferon alfa-2b and peginterferon alfa-2a. Relapse rates were 23.5% (95% CI, 19.9 to 27.2) for standard-dose peginterferon alfa-2b, 20.0% (95% CI, 16.4 to 23.6) for lowdose peginterferon alfa-2b, and 31.5% (95% CI, 27.9 to 35.2) for peginterferon alfa- 2a. The safety profile was similar among the three groups; serious adverse events were observed in 8.6 to 11.7% of patients. Among the patients with undetectable HCV RNA levels at treatment weeks 4 and 12, a sustained virologic response was achieved in 86.2% and 78.7%, respectively.
Conclusions
In patients infected with HCV genotype 1, the rates of sustained virologic response and tolerability did not differ significantly between the two available peginterferonâ ribavirin regimens or between the two doses of peginterferon alfa-2b. (ClinicalTrials. gov number, NCT00081770.
New Horizons in Agricultural Information Management : proceedings of an international symposium, 13-16 Mar. 1991, Beijing, China
Meeting: New Horizons in Agricultural Information Management, 13-16 Mar. 1991, Beijing, C
The Invisible Third. The Basque and Celtic Words for "Swallow"
In a keynote address at the XI. Fachtagung der Indogermanischen
Gesellschaft, about possible non-Indo-European influence on the Celtic
languages, Kim McCone drew attention to the similarity between the
Insular Celtic, e.g. OIr fannall, W gwennol, and the Basque,i.e. enara, ain(h)-
ara, words for 'swallow' (Lat hirundo). McCone reconstructs *waNilri or
*weNrilri as preforms for the Insular Celtic words, and *(w)aiNala for Pre-
Basque (McCone 2005,408-9).l This suggestion looks very attractive and
suggestive and, if correct, would shed rare light on prehistoric linguistic
relationships in Western Europe. In this article, I will examine the equation
more closely and add a number of observations
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4 HCV SPRINT-1 FINAL RESULTS: SVR 24 FROM A PHASE 2 STUDY OF BOCEPREVIR PLUS PEGINTRONâą (PEGINTERFERON ALFA-2B)/RIBAVIRIN IN TREATMENT- NAIVE SUBJECTS WITH GENOTYPE-1 CHRONIC HEPATITIS C
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