Objective To investigate the impact of edaravone on serum reactive oxygen species during the perioperative period of off-pump coronary artery bypass grafting （OPCAB）. Methods A total of 40 patients who underwent selective OPCAB in the First Hospital of Hebei Medical University between June 2011 and November 2012 were prospectively enrolled in this study. All the patients were randomly divided into a trial group and a control group by a random digitaltable method with 20 patients in each group. There were 13 males and 7 females in the trial group with their age of 40-67（51.8±11.5） years， and 9 males and 11 females in the control group with their age of 42-70 （53.5±13.1） years. Afteranesthesia induction， patients in the trial group received continuous intravenous infusion of edaravone 60 mg （diluted in 100 ml saline）， while patients in the control group received continuous intravenous infusion of saline 100 ml， both of whichwere finished within 30 minutes. Venous blood samples were taken 24 hours preoperatively （T1）， 1 hour after skin incision（T2）， at the end of the surgery （T3） and 24 hours postoperatively （T4） to examine the concentration of superoxide dismutase（SOD） and malondialdehyde （MDA）. The data of the two groups were compared. Results All the patients successfully underwent their surgery and were included in the analysis. At the T2， T3 and T4 time point， SOD concentration was 80.3±21.3 U/ml， 78.5±17.4 U/ml and 81.4±17.5 U/ml， and MDA concentration was 10.2±1.8 nmol/ml， 11.3±1.9 nmol/ml，14.8±2.1 nmol/ml respectively in the control group；SOD concentration was 92.8±18.4 U/ml，90.0±18.1 U/ml，and 88.7±18.7 U/ml，and MDA concentration was 7.2±1.7 nmol/ml，8.2±1.2 nmol/ml，10.2±1.3 nmol/ml respectively in the trial group. At each above time point， SOD activity was significantly higher in the trial group than the control group （F=2.90，P=0.003；F=2.80，P=0.003；F=2.80，P=0.001）， and MDA concentration was significantly lower in the trial group than the control group （F=2.79，P=0.001；F=2.80，P=0.001；F=2.90，P=0.000）. Conclusion Edaravone can decrease serum reactive oxygen species caused by OPCAB and reduce myocardial injury.
Objectives To assess the effectiveness and safety of carnitine in the treatment of idiopathic asthenozoospermia. Methods The Cochrane Library, MEDLINE, EMbase, and CNKI were searched between Jan 1995 and Dec 2006. Both English and Chinese studies were included in the review if they were randomized controlled trials (RCTs) involving men with idopathic asthenozoospermia who were treated with carnitine. Trial screening, data extraction, and quality assessment of included trials were conducted by method recommended by Cochrane Collaboration. Statistical analysis was conducted using RevMan 4.2.10 software. Results Five RCTs involving 346 patients met the inclusion criteria, and 307 patients were included in the meta-analysis. The results showed that: after being treated with carnitine for 3 and 6 months, the difference of the patients’ partners’ spontaneous pregnancy rate between treatment group and control group was statistically significant with RR2.46 and 95% CI1.12 to 5.43 (Z=2.23, P=0.03). After being treated with carnitine for 3 and 6 months, the difference of forward motile sperm per ejaculate between treatment group and control group was not statistically significant with WMD 9.16 and 95%CI 0.14 to 18.18 (Z=1.99, P=0.05) and WMD 5.28 and 95%CI –4.45 to 15.01 (Z=1.06, P=0.29). After being treated with carnitine for 3 and 6 months, the difference of percentage of forward sperm motility between treatment group and control group was not statistically significant with WMD 14.56 and 95%CI –4.49 to 33.61( Z=1.50 ,P=0.13), and WMD 7.34 and 95%CI –5.93 to 20.61 (Z=1.08, P=0.28). After being treated with carnitine for 3 and 6 months, the difference of total motile sperm per ejaculate between treatment group and control group was not statistically significant with WMD 15.32 and 95%CI –1.34 to 31.98 (Z=1.80, P=0.07) and WMD 6.20, 95%CI –3.00 to 15.39 (Z=1.32, P=0.19).After being treated with carnitine for 3 and 6 months, the difference of percentage of total sperm motility between treatment group and control group was not statistically significant with WMD 2.97 and 95%CI –5.75 to 11.69 (Z=0.67, P=0.50) and WMD 4.48 and 95%CI-9.17 to18.14 (Z=0.64, P=0.52). After being treated with carnitine for 3 and 6 months, the difference of semen volume between treatment group and control group was not statistically significant with WMD –0.12 and 95%CI –0.55 to 0.30 (Z=0.57, P=0.57) and WMD 0.03 and 95%CI –0.38 to 0.45 (Z=0.16, P=0.87). After being treated with carnitine for 3 and 6 months, the difference of sperm concentration between treatment group and control group was not statistically significant with WMD 7.92 and 95%CI – 2.85 to18.68 (Z=1.44, P=0.15), and WMD 1.02 and 95%CI –5.09 to 7.14 (Z=0.33, P=0.74). Three RCTs reported that there were no serious side effects of carnitine during the treatment period. Conclusions The available evidence indicates that spontaneous pregnancy rate would increase with carnitine therapy, while it is short of improvement of semen parameters. There is no serious side effect of carnitine. Because of lack of evidence, we cannot conclude that carnitine is effective in improving the prognosis of infertile patients with idiopathic asthenozoospermia. More high quality trials with large sample are proposed.
Economic evaluation used alongside clinical trials has become a hot spot in the development of clinical studies. The definition and classification of the cost were introduced in this article. The ways to conduct cost analysis in clinical trials were introduced systematically, including the identification, collection and analysis of the data of costs, and the concern of the analysis.
Objective To investigate the regulations and implementation effect for high-risk drugs of the FDA and MHRA on the basis of natalizumab, and to provide references for the risk regulation of the innovative drugs and high-risk drugs of China. Methods We searched MEDLINE, EMBASE.com, the official website of Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) for the marketing/withdrawal and risk regulation information of natalizumab as well as the relevant information of drug marketing/withdrawal and approval track. Results (1) Natalizumab was initially approved by the FDA through accelerated approval in November, 2004 with the phase three clinical trial still being conducted. But in February 2005, it was withdrawn after 3 patients developed PML. FDA resumed its marketing under a specially restricted distribution program called the Touch Prescribing Program in March, 2006. (2) Natalizumab was marketed in the European Union in April 2006. No cases of PML have been reported in the UK for this drug. (3) To speed the development of drugs that treat serious diseases, the FDA developed 3 distinct and successful approaches to make such drugs available as rapidly as possible: Priority Review, Accelerated Approval, and Fast Track. The proportion of new molecular entity and new biologic approved by fast tract were 45% and 74%, respectively between 2002 and 2009. (4) Drug regulation of MHRA contained: Yellow Card Scheme, Black Triangle products, Download Drug Analysis Prints (DAPs), and Defective Medicines Report Centre (DMRC). Self-reporting and monitoring system were fairly perfect, thus they can fulfill the close monitoring for high-risk drugs under the existing conditions and then realize the risk-minimization. Conclusion (1) The risk-minimization program of FDA for high-risk drugs is effective, and plays a role in the policy support for the researching and marketing of irreplaceable innovative drugs. (2) The risk regulation for high-risk drugs of MHRA is integrated into drug regulation program and enforces hierarchical management, and acquires risk-minimization effect. (3) We should learn from the policy and operational experience for the international new molecular entity and new biologic on the re-evaluation for innovative drugs and high-risk drugs. Combined with drug specific characteristics, evaluation indicators and criteria are developed base on evidence, risk management system and mechanism for innovative drugs are established and improved, and policy and administration security for the safety application of innovative drugs and high-risk drugs are provided.
Individual patient data meta-analyses are conducted through development of collaboration with trial investigators, central collection and checking of individual patient data of all eligible trials, and pooling of patient data to produce the best estimate of effects of health care interventions. They ensure study data to be update, accessible, reliable and complete so as to minimize the risk of bias, and are the gold standard of systematic reviews addressing effects of health care interventions. Meta-analyses using individual patient data enable higher flexibility of data analyses and more completeness and balance of results interpretation. The study conduct differs between individual patient data versus conventional meta-analyses. This article discussed the steps of conducting individual patient data meta-analyses.