Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C

Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14 days. Previously untreated patients with genotype 1 hepatitis C were randomized to receive placebo and peginterferon alfa-2a (n = 4); telaprevir (n = 8); or telaprevir and peginterferon alfa-2a (n = 8). Telaprevir was given as 750 mg oral doses every 8 hours; peginterferon alfa-2a was given as weekly 180 mug subcutaneous injections. The median change in HCV RNA from baseline to day 15 was -1.09 log(10) (range, -2.08 to -0.46) in the placebo and peginterferon alfa-2a group; -3.99 log(10) (range, -5.28 to -1.26) in the telaprevir group, and -5.49 log(10) (range, -6.54 to -4.30) in the telaprevir and peginterferon alfa-2a group. Day 15 HCV RNA levels were undetectable in 4 patients who received telaprevir and peginterferon alfa-2a and in 1 patient who received telaprevir alone. No viral breakthrough occurred in patients who received telaprevir and peginterferon alfa-2a. The majority of adverse events were mild. There were no serious adverse events or premature discontinuations. Twelve weeks after starting off-study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa-2a group, 5 patients in the telaprevir group, and 1 patient in the placebo and peginterferon alfa-2a group. CONCLUSION: This study confirmed the substantial antiviral effects of telaprevir and showed an increased antiviral effect of telaprevir combined with peginterferon alfa-2

Telaprevir and peginterferon with or without ribavirin for chronic HCV infection.: PROVE2: Telaprevir with PEG-IFN and RBV in HCV

International audienceBACKGROUND: In patients with chronic infection with hepatitis C virus (HCV) genotype 1, treatment with peginterferon alfa and ribavirin for 48 weeks results in rates of sustained virologic response of 40 to 50%. Telaprevir is a specific inhibitor of the HCV serine protease and could be of value in HCV treatment. METHODS: A total of 334 patients who had chronic infection with HCV genotype 1 and had not been treated previously were randomly assigned to receive one of four treatments involving various combinations of telaprevir (1250 mg on day 1, then 750 mg every 8 hours), peginterferon alfa-2a (180 microg weekly), and ribavirin (dose according to body weight). The T12PR24 group (81 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks, followed by peginterferon alfa-2a and ribavirin for 12 more weeks. The T12PR12 group (82 patients) received telaprevir, peginterferon alfa-2a, and ribavirin for 12 weeks. The T12P12 group (78 patients) received telaprevir and peginterferon alfa-2a without ribavirin for 12 weeks. The PR48 (control) group (82 patients) received peginterferon alfa-2a and ribavirin for 48 weeks. The primary end point, a sustained virologic response (an undetectable HCV RNA level 24 weeks after the end of therapy), was compared between the control group and the combined T12P12 and T12PR12 groups. RESULTS: The rate of sustained virologic response for the T12PR12 and T12P12 groups combined was 48% (77 of 160 patients), as compared with 46% (38 of 82) in the PR48 (control) group (P=0.89). The rate was 60% (49 of 82 patients) in the T12PR12 group (P=0.12 for the comparison with the PR48 group), as compared with 36% (28 of 78 patients) in the T12P12 group (P=0.003; P=0.20 for the comparison with the PR48 group). The rate was significantly higher in the T12PR24 group (69% [56 of 81 patients]) than in the PR48 group (P=0.004). The adverse events with increased frequency in the telaprevir-based groups were pruritus, rash, and anemia. CONCLUSIONS: In this phase 2 study of patients infected with HCV genotype 1 who had not been treated previously, one of the three telaprevir groups had a significantly higher rate of sustained virologic response than that with standard therapy. Response rates were lowest with the regimen that did not include ribavirin. (ClinicalTrials.gov number, NCT00372385.

Turbulent Thermal Image Velocimetry at the Immediate Fire and Atmospheric Interface

We present novel in-field vegetation fire observations and the analyses using brightness temperatures recorded by longwave infrared camera and thermal image velocimetry. The brightness temperatures from a wind-driven stubble wheat fire were obtained with a 60 frames per second (fps) video acquisition. Multi-level sonic anemometers on a 10m in-fire tower were used for measurements of turbulent velocity and air temperatures, while fuel level air and flame temperatures were collected by an array of thermocouples (TCs). The camera\u27s image pixel resolution was adequate to discern thermal structures in accordance with the in-fire TC measurements and its spacing distances. The in-situ and remotely measured flaming zone dynamics were derived using two different methodologies, Thermal Image Velocimetry (TIV) and Image Segmentation (IS). The results highlight spatial and spectral information of coherent turbulent and mean velocity structures. The power spectra decomposition of the TIV showed similar spectral characteristics to the sonic speed measurements during the fire passage under the tower with a similar inertial subrange slope. This result reveals plausible evidence of interaction between the flaming zone and wind turbulence for a prescribed rapidly moving stubble wheat fire. This research presents a new field measurement methodology for understanding fire-atmospheric interactions between the flaming zone and the immediate overlying atmospheric turbulent boundary layer

Sexual orientation and treatment-seeking for depression in a multilingual worldwide sample

BACKGROUND: Prior research has found higher rates of mental health problems among sexual minority individuals. We examine treatment-seeking for depression, as well as its relationship with sexual orientation, in a large, multilingual, international sample. METHOD: Participants in an automated, quintilingual internet-based depression screening tool were screened for depression, and completed several background measures, including sexual orientation (with an option to decline to state) and past and current depression treatment seeking. RESULTS: 3,695 participants screened positive for current or past depression and responded to the sexual orientation question. Those who declined to state their sexual orientation were far less likely to seek any treatment than individuals endorsing any orientation; they were especially unlikely to seek psychotherapy. Individuals identifying as bisexual sought both psychotherapy and alternative treatments at a higher rate than other groups. An interaction was observed between sexual orientation and gender, such that lesbian women were especially likely to have used psychotherapy. Other variables that emerged as significant predictors of treatment-seeking for depression included age and participant's language. LIMITATIONS: Limitations include possible misinterpretation of translated terms due to regional differences, and possible limits to generalizability due to this study being conducted on the internet. CONCLUSIONS: Our results suggest that individuals who decline to state their sexual orientation may be more likely to forgo effective treatments for depression. Further studies of depression service utilization should focus on developing treatment modalities that could better engage sexual minority individuals, especially those who are reluctant to disclose their orientation

Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants

ObjectiveTo compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation.Study designMulticenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-246/7 and 25-286/7 weeks.ResultsAmong 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.ConclusionsThis analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH.Trial registrationClinicalTrials.gov: NCT00063063

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