People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen ... more People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was undetectable HCV RNA (<15 IU/mL) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part...
Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic re... more Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) following 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). In 2 phase 3, open-label trials, patients with HCV infection who had not previously been treated with a direct-acting antiviral agent were randomly assigned to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the non-inferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a non-inferiority margin of 5%. POLARIS...
The best regimen to retreat patients who do not respond to direct-acting antivirals (DAAs) and th... more The best regimen to retreat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus (HCV) genotype 1 infection. We performed an open-label trial at 32 sites in the United States and 2 sites in New Zealand of 197 patients with genotype 1 HCV infection, with or without compensated cirrhosis, who were treatment-naïve or previously treated with a DAA. Between March 2 and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for one treatment group consisting of treatment-naïve patients with cirrhosis. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Among t...
American Journal of Infection Control, Jan 2, 2009
Between April and June 2007, an outbreak of extended-spectrum beta-lactamase-producing Klebsiella... more Between April and June 2007, an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infections occurred in an intensive care unit in New Jersey. The outbreak was contained through active microbiologic surveillance, contact precautions, cohorting, and frequent room cleaning. This outbreak demonstrates the importance of rapid response in identifying and isolating patients to prevent further transmission.
Effective antiviral therapy is essential for achieving sustained virological response (SVR) in he... more Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naïve and prior null-responder HCV genotype (GT)1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12/24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naïve and -experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence/absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily (QD)+sofosbuvir 400 mg QD for 12 or 8 weeks. Primary efficacy endpoint: SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 ...
Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of ... more Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of this study was to identify whether currently prescribed doses of cefoxitin achieve adequate and sustained plasma and tissue concentrations in obese patients undergoing sleeve gastrectomy. A prospective evaluation of plasma and tissue cefoxitin concentrations in patients undergoing sleeve gastrectomy was performed. On the day of the surgical procedure, venous blood samples (5 mL) were collected just before cefoxitin administration and then at 5, 30, 60, 120, and 240 minutes after dose administration. In addition, subcutaneous adipose tissue was collected from the surgical site at the time of surgical incision and at closure. Cefoxitin concentrations in the collected samples were quantified by using an HPLC-ultraviolet method. A standard noncompartmental analysis was performed for each individual cefoxitin plasma concentration-time profile. In addition, the ratio of tissue to plasma concentration was calculated for all patients. Plasma and tissue pharmacokinetics of cefoxitin were evaluated in 6 patients undergoing sleeve gastrectomy. The mean age and BMI were 48.7 (6.2) years and 42.8 (7.1) kg/m(2), respectively. At the time of surgical closure, subcutaneous adipose tissue concentrations of cefoxitin were subtherapeutic (&amp;amp;amp;amp;amp;amp;amp;amp;lt;8 µg/mL) in all evaluated patients. Current dosing strategies for cefoxitin in obese surgical patients may be inadequate, and there is an urgent need to define the appropriate dosage.
Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. To assess th... more Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). 48 U.S. sites. 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. Sustained virologic response at 12 weeks (SVR12). In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In p...
People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen ... more People with hepatitis C virus (HCV) infection who have failed treatment with an all-oral regimen represent a challenging treatment population. The present studies evaluated the safety and efficacy of grazoprevir, ruzasvir, and uprifosbuvir, with or without ribavirin, in participants who had failed an NS5A inhibitor-containing regimen. C-SURGE (PN-3682-021) and C-CREST Part C (PN-3682-011 and -012) were open-label, multicenter studies. Participants who had previously relapsed following an NS5A inhibitor-containing all-oral regimen were retreated with grazoprevir 100 mg, ruzasvir 60 mg, and uprifosbuvir 450 mg alone for 24 weeks or with ribavirin for 16 weeks. The primary efficacy endpoint was undetectable HCV RNA (<15 IU/mL) 12 weeks after treatment completion (SVR12). In C-SURGE, SVR12 was achieved by 49/49 (100%) and 43/44 (98%) genotype (GT)1 participants in the 24-week no ribavirin arm and the 16-week plus ribavirin arm (lost to follow-up, n = 1), respectively. In C-CREST Part...
Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic re... more Patients with chronic hepatitis C virus (HCV) infection have high rates of sustained virologic response (SVR) following 12 weeks of treatment with the nucleotide polymerase inhibitor sofosbuvir combined with the NS5A inhibitor velpatasvir. We assessed the efficacy of 8 weeks of treatment with sofosbuvir and velpatasvir plus the pangenotypic NS3/4A protease inhibitor voxilaprevir (sofosbuvir-velpatasvir-voxilaprevir). In 2 phase 3, open-label trials, patients with HCV infection who had not previously been treated with a direct-acting antiviral agent were randomly assigned to groups given sofosbuvir-velpatasvir-voxilaprevir for 8 weeks or sofosbuvir-velpatasvir for 12 weeks. POLARIS-2, which enrolled patients infected with all HCV genotypes with or without cirrhosis, except patients with genotype 3 and cirrhosis, was designed to test the non-inferiority of 8 weeks of sofosbuvir-velpatasvir-voxilaprevir to 12 weeks of sofosbuvir-velpatasvir using a non-inferiority margin of 5%. POLARIS...
The best regimen to retreat patients who do not respond to direct-acting antivirals (DAAs) and th... more The best regimen to retreat patients who do not respond to direct-acting antivirals (DAAs) and the feasibility of further shortening regimens is unclear. We assessed the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in patients with hepatitis C virus (HCV) genotype 1 infection. We performed an open-label trial at 32 sites in the United States and 2 sites in New Zealand of 197 patients with genotype 1 HCV infection, with or without compensated cirrhosis, who were treatment-naïve or previously treated with a DAA. Between March 2 and September 1, 2015, patients received sofosbuvir-velpatasvir (400 mg/100 mg in a fixed-dose combination) plus GS-9857 (100 mg) once daily for 6-12 weeks, plus ribavirin for one treatment group consisting of treatment-naïve patients with cirrhosis. The primary endpoint was sustained virologic response 12 weeks after treatment (SVR12). Among t...
American Journal of Infection Control, Jan 2, 2009
Between April and June 2007, an outbreak of extended-spectrum beta-lactamase-producing Klebsiella... more Between April and June 2007, an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae infections occurred in an intensive care unit in New Jersey. The outbreak was contained through active microbiologic surveillance, contact precautions, cohorting, and frequent room cleaning. This outbreak demonstrates the importance of rapid response in identifying and isolating patients to prevent further transmission.
Effective antiviral therapy is essential for achieving sustained virological response (SVR) in he... more Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naïve and prior null-responder HCV genotype (GT)1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12/24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naïve and -experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence/absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily (QD)+sofosbuvir 400 mg QD for 12 or 8 weeks. Primary efficacy endpoint: SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 ...
Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of ... more Antibiotic dosing in obese surgical patients has not been adequately evaluated. The objective of this study was to identify whether currently prescribed doses of cefoxitin achieve adequate and sustained plasma and tissue concentrations in obese patients undergoing sleeve gastrectomy. A prospective evaluation of plasma and tissue cefoxitin concentrations in patients undergoing sleeve gastrectomy was performed. On the day of the surgical procedure, venous blood samples (5 mL) were collected just before cefoxitin administration and then at 5, 30, 60, 120, and 240 minutes after dose administration. In addition, subcutaneous adipose tissue was collected from the surgical site at the time of surgical incision and at closure. Cefoxitin concentrations in the collected samples were quantified by using an HPLC-ultraviolet method. A standard noncompartmental analysis was performed for each individual cefoxitin plasma concentration-time profile. In addition, the ratio of tissue to plasma concentration was calculated for all patients. Plasma and tissue pharmacokinetics of cefoxitin were evaluated in 6 patients undergoing sleeve gastrectomy. The mean age and BMI were 48.7 (6.2) years and 42.8 (7.1) kg/m(2), respectively. At the time of surgical closure, subcutaneous adipose tissue concentrations of cefoxitin were subtherapeutic (&amp;amp;amp;amp;amp;amp;amp;amp;lt;8 µg/mL) in all evaluated patients. Current dosing strategies for cefoxitin in obese surgical patients may be inadequate, and there is an urgent need to define the appropriate dosage.
Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. To assess th... more Effective, pangenotypic treatments for hepatitis C virus (HCV) infection are needed. To assess the safety and efficacy of sofosbuvir with velpatasvir in patients infected with HCV genotypes 1 to 6. Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01858766). 48 U.S. sites. 377 treatment-naive noncirrhotic patients. In part A, patients infected with HCV genotypes 1 to 6 were randomly assigned to sofosbuvir, 400 mg, with velpatasvir, 25 or 100 mg, for 12 weeks. In part B, patients with genotype 1 or 2 HCV infection were randomly assigned to sofosbuvir, 400 mg, and velpatasvir, 25 or 100 mg, with or without ribavirin for 8 weeks. Sustained virologic response at 12 weeks (SVR12). In part A, SVR12 rates were 96% (26 of 27) with velpatasvir, 25 mg, and 100% (28 of 28) with velpatasvir, 100 mg, for genotype 1; 93% (25 of 27) in both groups for genotype 3; and 96% (22 of 23) with velpatasvir, 25 mg, and 95% (21 of 22) with velpatasvir, 100 mg, for genotypes 2, 4, 5, and 6. In p...
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