The New England journal of medicine
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Randomized Controlled Trial Multicenter Study
Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1.
An interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the nonnucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection. The addition of another potent agent, the NS5A inhibitor ABT-267, may improve efficacy, especially in difficult-to-treat patients. This study was designed to evaluate multiple regimens of direct-acting antiviral agents and ribavirin in patients with HCV genotype 1 infection who had not received therapy previously or who had no response to prior therapy with pegylated interferon and ribavirin. ⋯ In this phase 2b study, all-oral regimens of antiviral agents and ribavirin were effective both in patients with HCV genotype 1 infection who had not received therapy previously and in those who had not had a response to prior therapy. (Funded by AbbVie; ClinicalTrials.gov number, NCT01464827.).
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Randomized Controlled Trial Multicenter Study
Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCV infection.
All-oral combination therapy is desirable for patients with chronic hepatitis C virus (HCV) infection. We evaluated daclatasvir (an HCV NS5A replication complex inhibitor) plus sofosbuvir (a nucleotide analogue HCV NS5B polymerase inhibitor) in patients infected with HCV genotype 1, 2, or 3. ⋯ Once-daily oral daclatasvir plus sofosbuvir was associated with high rates of sustained virologic response among patients infected with HCV genotype 1, 2, or 3, including patients with no response to prior therapy with telaprevir or boceprevir. (Funded by Bristol-Myers Squibb and Pharmasset (Gilead); A1444040 ClinicalTrials.gov number, NCT01359644.).
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Endotracheal extubation should be performed without causing trauma, while maintaining adequate oxygenation and ventilation. The equipment needed to provide suction, ventilation, and reintubation should be readily available. ⋯ Before performing extubation, the clinician must carefully prepare the medical resources needed to address reasonably foreseeable complications. A failed extubation can lead to a precipitous deterioration in the patient's condition, and attempts to improvise solutions under these challenging circumstances are rarely satisfactory.