Bivalirudin vs heparin with or without tirofiban during primary percutaneous coronary intervention in acute myocardial infarction: the BRIGHT randomized clinical trial.

IMPORTANCE: The safety and efficacy of bivalirudin compared with heparin with or without glycoprotein IIb/IIIa inhibitors in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are uncertain. OBJECTIVE: To determine if bivalirudin is superior to heparin alone and to heparin plus tirofiban during primary PCI. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, open-label trial involving 2194 patients with AMI undergoing primary PCI at 82 centers in China between August 2012 and June 2013. INTERVENTIONS: Patients were randomly assigned to receive bivalirudin with a post-PCI infusion (n = 735), heparin alone (n = 729), or heparin plus tirofiban with a post-PCI infusion (n = 730). Among patients treated with bivalirudin, a postprocedure 1.75 mg/kg/h infusion was administered for a median of 180 minutes (IQR, 148-240 minutes). MAIN OUTCOMES AND MEASURES: The primary end point was 30-day net adverse clinical events, a composite of major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or bleeding. Additional prespecified safety end points included the rates of acquired thrombocytopenia at 30 days, and stent thrombosis at 30 days and 1 year. RESULTS: Net adverse clinical events at 30 days occurred in 65 patients (8.8%) of 735 who were treated with bivalirudin compared with 96 patients (13.2%) of 729 treated with heparin (relative risk [RR], 0.67; 95% CI, 0.50-0.90; difference, -4.3%, 95% CI, -7.5% to -1.1%; P = .008); and 124 patients (17.0%) of 730 treated with heparin plus tirofiban (RR for bivalirudin vs heparin plus tirofiban, 0.52; 95% CI, 0.39-0.69; difference, -8.1%, 95% CI, -11.6% to -4.7%; P < .001). The 30-day bleeding rate was 4.1% for bivalirudin, 7.5% for heparin, and 12.3% for heparin plus tirofiban (P < .001). There were no statistically significant differences between treatments in the 30-day rates of major adverse cardiac or cerebral events (5.0% for bivalirudin, 5.8% for heparin, and 4.9% for heparin plus tirofiban, P = .74), stent thrombosis (0.6% vs 0.9% vs 0.7%, respectively, P = .77), acquired thrombocytopenia (0.1% vs 0.7% vs 1.1%; P = .07), or in acute (<24-hour) stent thrombosis (0.3% in each group). At the 1-year follow-up, the results remained similar. CONCLUSIONS AND RELEVANCE: Among patients with AMI undergoing primary PCI, the use of bivalirudin with a median 3-hour postprocedure PCI-dose infusion resulted in a decrease in net adverse clinical events compared with both heparin alone and heparin plus tirofiban. This finding was primarily due to a reduction in bleeding events with bivalirudin, without significant differences in major adverse cardiac or cerebral events or stent thrombosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01696110.

[Efficacy and safety of intravenous levosimendan compared with dobutamine in decompensated heart failure].

OBJECTIVE: To compare the efficacy and safety of intravenous levosimendan and dobutamine in patients with decompensated heart failure refractory to conventional medications. METHODS: Patients were recruited into this multicentre, randomised, positive-controlled and parallel-group study to receive either levosimendan or dobutamine therapy. In the levosimendan group, an initial loading dose of levosimendan of 12 microg x kg was infused over 10 min, followed by a continuous infusion of 0.1 microg x kg(-1) x min(-1) for 1 h and then 0.2 microg x kg(-1) x min(-1) for 23 h. In the control group, dobutamine was infused for 1 h at an initial dose of 2 microg x kg(-1) x min(-1) without a loading dose, followed by a continuous infusion of 4 microg x kg(-1) x min(-1) for 23 h. Hemodynamic responses at 24 h were evaluated by echocardiography (in both groups) and Swan-Gans catheter (in the levosimendan group). Clinical assessment was performed to evaluate efficacy and safety of the medications. RESULTS: A total of 225 patients from 12 medical centers were evaluated; 119 assigned to levosimendan and 106 assigned to dobutamine group. The effectiveness rate was 31.9% (38 patients) in the levosimendan group and 17.9% (19 patients) in the dobutamine group (P < 0.01). At 24 h, left ventricular ejection fraction (LVEF) was improved by 6. 4% in the levosimendan group, compared with 4.6% in the dobutamine group (P > 0.05). Stroke volume (SV) was increased by 11.1 ml in the levosimendan group and 2.8 ml in the dobutamine group respectively (P < 0.05). Dyspnea and clinical manifestations improvements were more significant in levosimendan therapy group compared to dobutamine group. There were less adverse effects including hypokalemia, hypotension and ventricular premature beats in the levosimendan group than in the dobutamine group (P < 0.05). CONCLUSION: Levosimendan was well tolerated and superior to dobutamine for patients with decompensated heart failure refractory to conventional medications.

Nicotinamide overload may play a role in the development of type 2 diabetes.

AIM: To investigate whether nicotinamide overload plays a role in type 2 diabetes. METHODS: Nicotinamide metabolic patterns of 14 diabetic and 14 non-diabetic subjects were compared using HPLC. Cumulative effects of nicotinamide and N(1)-methylnicotinamide on glucose metabolism, plasma H(2)O(2) levels and tissue nicotinamide adenine dinucleotide (NAD) contents of adult Sprague-Dawley rats were observed. The role of human sweat glands and rat skin in nicotinamide metabolism was investigated using sauna and burn injury, respectively. RESULTS: Diabetic subjects had significantly higher plasma N(1)-methylnicotinamide levels 5 h after a 100-mg nicotinamide load than the non-diabetic subjects (0.89 +/- 0.13 micromol/L vs 0.6 +/- 0.13 micromol/L, P < 0.001). Cumulative doses of nicotinamide (2 g/kg) significantly increased rat plasma N(1)-methylnicotinamide concentrations associated with severe insulin resistance, which was mimicked by N(1)-methylnicotinamide. Moreover, cumulative exposure to N(1)-methylnicotinamide (2 g/kg) markedly reduced rat muscle and liver NAD contents and erythrocyte NAD/NADH ratio, and increased plasma H(2)O(2) levels. Decrease in NAD/NADH ratio and increase in H(2)O(2) generation were also observed in human erythrocytes after exposure to N(1)-methylnicotinamide in vitro. Sweating eliminated excessive nicotinamide (5.3-fold increase in sweat nicotinamide concentration 1 h after a 100-mg nicotinamide load). Skin damage or aldehyde oxidase inhibition with tamoxifen or olanzapine, both being notorious for impairing glucose tolerance, delayed N(1)-methylnicotinamide clearance. CONCLUSION: These findings suggest that nicotinamide overload, which induced an increase in plasma N(1)-methylnicotinamide, associated with oxidative stress and insulin resistance, plays a role in type 2 diabetes.

Changing knowledge, behavior, and practice related to universal precautions among hospital nurses in China.

PURPOSE: To evaluate the effect of an educational training program for hospital nurses on universal precautions in Changsha, Hunan Province, People's Republic of China. METHOD: Using a quasi-experimental design, 50 of 100 randomly selected hospital nurses were randomly assigned to receive an educational intervention. Questionnaires were administered to the 100 nurses prior to and 4 months after the training. FINDINGS: Knowledge, practice, and behaviors related to universal precautions and the prevalence of hepatitis B immunization improved among nurses in the group who received training. No significant change in the frequency of glove use was found. Underreporting of sharps injuries to hospital authorities continued in both groups. CONCLUSION: Although educational training significantly improved Chinese nurses' knowledge, practice, and behavior related to universal precautions, there remains room for improvement in glove use and needlestick injury reporting.