AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, ...
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AIMTo evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial. METHODSA prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR). RESULTSA total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P = 0.09). CONCLUSIONThe trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.
Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this ex...
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Linked to major volcanic eruptions around 536 and 540 CE, the onset of the Late Antique Little Ice Age has been described as the coldest period of the past two millennia. The exact timing and spatial extent of this exceptional cold phase are, however, still under debate because of the limited resolution and geographical distribution of the available proxy archives. Here, we use 106 wood anatomical thin sections from 23forest sites and 20 tree species in both hemispheres to search for cell-level fingerprints of ephemeral summer cooling between 530 and 550 CE. After cross-dating and double-staining, we identified 89Blue Rings(lack of cell wall lignification), nine Frost Rings(cell deformation and collapse), and 93Light Rings(reduced cell wall thickening) in the Northern Hemisphere. Our network reveals evidence for the strongest temperature depression between mid-July and early-August 536 CE across North America and Eurasia, whereas more localised cold spells occurred in the summers of 532, 540–43, and548 CE. The lack of anatomical signatures in the austral trees suggests limited incursion of stratospheric volcanic aerosol into the Southern Hemisphere extra-tropics, that any forcing was mitigated by atmosphere-ocean dynamical responses and/or concentrated outside the growing season, or a combination of factors. Our findings demonstrate the advantage of wood anatomical investigations over traditional dendrochronological measurements, provide a benchmark for Earth system models, support cross-disciplinary studies into the entanglements of climate and history, and question the relevance of global climate averages.
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