Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated wi...Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated with hypercholesterolemia and drug interactions. For this study, we examined a dual strategy to manage hypertriglyceridemia in HIV-infected patient taking PIs: 1) switching patients to fosamprenavir (FPV), a PI with fewer drug interactions, and 2) adding prescription fish oil (LOVAZA?), which has been shown to reduce triglycerides. Methods: This multicenter, 24-week study enrolled 36 patients virologically suppressed (HIV-1 RNA <50 copies/mL) on PI-containing therapy with screening triglyceride levels of 200 - 1200 mg/dL and LDL cholesterol levels ≤160 mg/dL. At baseline, patients were switched to ritonavir (RTV)-boosted fosamprenavir (FPV 1400 mg/RTV 100 mg QD) and any lipid-lowering agents were stopped. At Week 6, LOVAZA 4 g QD was added. Results: Five patients prematurely discontinued due to adverse events (2), non-compliance, lost-to-follow up, and protocol violation. Median triglyceride concentration was 303 mg/dL at screening, 262 mg/dL at baseline, 290 mg/dL at Week 6 (+8% from baseline), and 218 mg/dL at Week 24 (–30% from Week 6). At Week 24, 39% (12/31) of patients had triglycerides <200 mg/dL. Among patients reaching Week 24, 100% (31/31) and 90% (28/31) had HIV-1 RNA <400 and <50 copies/mL, respectively. Conclusions: In this study, a switch to FPV/RTV followed by LOVAZA decreased median triglyceride levels and modestly increased the percentage of patients with triglyceride levels <200 mg/dL while maintaining virologic suppression in HIV-infected subjects with hypertriglyceridemia. Our data suggest that baseline PI may affect the likelihood of achieving triglycerides <200 mg/dL after 18 weeks on study. A larger study would be needed to understand the relative contributions of choice of protease inhibitor and LOVAZA to triglyceride concentrations in HIV-infected patients.展开更多
All in black,over one thousand textile executives from the country are gathering here in Babaoshan public cemetery,west of Beijing,on the morning of April 30,just one day before Chinese"golden holidays"of it...All in black,over one thousand textile executives from the country are gathering here in Babaoshan public cemetery,west of Beijing,on the morning of April 30,just one day before Chinese"golden holidays"of its week-long International Laborers’ Days starting from May 1st.This is展开更多
Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce...Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma growth.Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical framework.Hypothesis In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of 0.05.An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching placebo.Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.Discussion We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments.展开更多
文摘Background: Managing hypertriglyceridemia in HIV-infected patients often requires multiple pharmacologic strategies. Many protease inhibitors (PIs), one of 6 classes of drugs used to treat HIV, have been associated with hypercholesterolemia and drug interactions. For this study, we examined a dual strategy to manage hypertriglyceridemia in HIV-infected patient taking PIs: 1) switching patients to fosamprenavir (FPV), a PI with fewer drug interactions, and 2) adding prescription fish oil (LOVAZA?), which has been shown to reduce triglycerides. Methods: This multicenter, 24-week study enrolled 36 patients virologically suppressed (HIV-1 RNA <50 copies/mL) on PI-containing therapy with screening triglyceride levels of 200 - 1200 mg/dL and LDL cholesterol levels ≤160 mg/dL. At baseline, patients were switched to ritonavir (RTV)-boosted fosamprenavir (FPV 1400 mg/RTV 100 mg QD) and any lipid-lowering agents were stopped. At Week 6, LOVAZA 4 g QD was added. Results: Five patients prematurely discontinued due to adverse events (2), non-compliance, lost-to-follow up, and protocol violation. Median triglyceride concentration was 303 mg/dL at screening, 262 mg/dL at baseline, 290 mg/dL at Week 6 (+8% from baseline), and 218 mg/dL at Week 24 (–30% from Week 6). At Week 24, 39% (12/31) of patients had triglycerides <200 mg/dL. Among patients reaching Week 24, 100% (31/31) and 90% (28/31) had HIV-1 RNA <400 and <50 copies/mL, respectively. Conclusions: In this study, a switch to FPV/RTV followed by LOVAZA decreased median triglyceride levels and modestly increased the percentage of patients with triglyceride levels <200 mg/dL while maintaining virologic suppression in HIV-infected subjects with hypertriglyceridemia. Our data suggest that baseline PI may affect the likelihood of achieving triglycerides <200 mg/dL after 18 weeks on study. A larger study would be needed to understand the relative contributions of choice of protease inhibitor and LOVAZA to triglyceride concentrations in HIV-infected patients.
文摘July 1st,an important day to mark summer arrival not according to Chinese lunar calendar,but to the habitual way of thinking that hot season sets in.
文摘All in black,over one thousand textile executives from the country are gathering here in Babaoshan public cemetery,west of Beijing,on the morning of April 30,just one day before Chinese"golden holidays"of its week-long International Laborers’ Days starting from May 1st.This is
基金Medical Research Future Fund,Australia(APP1152282).
文摘Rationale Haematoma growth is common early after intracerebral haemorrhage(ICH),and is a key determinant of outcome.Tranexamic acid,a widely available antifibrinolytic agent with an excellent safety profile,may reduce haematoma growth.Methods and design Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units(STOP-MSU)is a phase Ⅱ double-blind,randomised,placebo-controlled,multicentre,international investigator-led clinical trial,conducted within the estimand statistical framework.Hypothesis In patients with spontaneous ICH,treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo.Sample size estimates A sample size of 180 patients(90 in each arm)would be required to detect an absolute difference in the primary outcome of 20%(placebo 39%vs treatment 19%)under a two-tailed significance level of 0.05.An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients.Intervention Participants will receive 1 g intravenous tranexamic acid over 10 min,followed by 1 g intravenous tranexamic acid over 8 hours;or matching placebo.Primary efficacy measure The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours,defined as either≥33%relative increase or≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan.Discussion We describe the rationale and protocol of STOP-MSU,a phase Ⅱ trial of tranexamic acid in patients with ICH within 2 hours from onset,based in participating mobile stroke units and emergency departments.
