Objective To study the effects and adverse reaction of imatinib mesylate used to prevent the recurrence of gastrointestinal stromal tumor (GIST) after resection. Methods 22 patients with primary gastrointestinal stromal tumor were included in the First Affiliated Hospital of Chongqing Medical University from January, 2007 to November, 2009 who received resection and were imageologically diagnosed as no residual tumor by enhanced CT or enhanced MRI after resection. They were all given imatinib mesylate 400 mg for oral use daily after resection (median-risk GIST: more than 1 year; high-risk GIST: more than 2 years). Patients’ 1-year and 2-year relapse-free survival (RFS) and adverse reaction were recorded during follow-up. Results Among 22 patients, there were 13 males and 9 females, with median age of 57.4 years, and 9 high-risk cases were included. The median follow-up lasted 34 months (24 to 48 months). Patients’ 1-year and 2-year RFS was 100% and 94.5%, respectively. Adverse reaction mainly included edema, nausea, abdominal pain, muscle or bone pain, thrombocytopenia, weakness, skin rashes, etc., most of which were mild or moderate and could be alleviated after treating symptoms. Conclusion Imatinib mesylate therapy given after resection is a safe and reliable method which could prolong RFS and prevent or delay the recurrence of GIST. However, further high-quality randomized controlled trial was required to verify its curative effects, since no control group has been set in our study.
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.
ObjectiveTo summarize the recent advancements in the researches on the pathogenesis of postoperative ileus and explain the clinical significances of postoperative ileus mechanisms for the diagnosis, treatment, and prevention. MethodsRelevant literatures about the postoperative ileus mechanism published recently were collected and reviewed. ResultsThe occurrence of postoperative ileus were related to postoperative nerve reflex inhibition, inflammatory response, effects of drugs, and other factors, it was a variety of mechanisms modulating each other. ConclusionThe gastrointestinal motility of postoperative ileus is mainly regulated by neural reflexes, inflammatory reactions, and drug interactions, three of which act differently but as a whole in different time segments while the inflammatory response play a key role of postoperative ileus persistence.
Objective To investigate the expression of granulysin ( GNLY) in lung of rats with acute lung injury ( ALI) stimulated with lipopolysaccharide ( LPS) . Methods Thirty-six healthy adult Wistar rats were randomly divided into a normal control group and a LPS group, with 18 rats in each group. LPS ( 4 mg/kg) was given intraperitoneally in the LPS group to induce ALI. The same amount of normal saline was given in the control group. The rats were randomly assigned to three subgroups ( n = 6) to be sacrificed respectively at 6, 18, and 30 hours after intraperitoneal injection. Wet/dry lung weight ratio ( W/D) and pathological changes of the lung were observed. The expression of GNLY in lung tissue was assayed by immunohistochemistry. Results In the LPS group, the W/D ratio was higher than that of the control group at each time point ( P lt;0. 05) and there were a large number of inflammatory cells infiltration and edema in interstitial spaces which suggested ALI. Compared with the control group, the expression of GNLY in the LPS group was significantly increased at all time points ( P lt;0. 05) . Conclusion GNLY may participate in ALI inflammatory process, which might play a role in preventing infection induced ALI.
Objective To establish standards, methods and processes for evidence-based evaluation and selection of essential medicine that meet the needs of the 8 pilot township health centers in China. Methods A descriptive analysis was conducted to compare the similarities/differences and the advantages/disadvantages of the standards, methods and processes between the World Health Organization (WHO) essential medicines evaluation and selection, and the GRADE evidence quality and recommend intensity. In combination with the former outcomes of this series of study, the standards, methods and processes of evidence-based evaluation and selection of essential medicines in the domestic pilot township health centers were optimized, restructured and improved. Softwares such as GRADEprofiler were used to assess the quality of evidence. Results a) Localized standards, methods and processes for evidence-based evaluation and selection of essential medicine were established, and the evaluation tool was ascertained; and b) Disease and drug names, guidelines and searching processes for evaluation and selection of essential medicine were developed with standardized, systematic and transparent approaches. Conclusion a) Standards, methods and processes for searching, evaluating and recommending the best evidence are preliminarily established, through comparative analysis on the effectiveness, safety, cost-effectiveness and applicability of the candidate medicines for diagnosing, treating and preventing diseases in township health centers in China; b) Following the principle of “utilizing the best existing evidences and developing the urgently-needed but lacking evidence”, a good exploration was done for the localization, standardization and transparency of the standards, methods and processes of evidence-based evaluation and selection of essential medicine for pilot township health centers.
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.
Objective To analyze the withdrawal reason of natalizumab in depth based on the serious adverse reaction reports and approval channel, and to provide decision references for more safe and effective report method of other biologicals. Methods We searched MEDLINE, EMbase, and the official websites of Food and Drug Administration (FDA) for case reports, approval channel, and the relevant information of drug marketing or withdrawal. Results Four case reports and fourteen official reports were included. Three cases of progressive multifocal leukoencephalopathy (PML) were reported in the clinical trials after natalizumab’s initially approval with two dead and one disabled, which could be retrieved by hemodialysis (2 cases hitherto). Consequently, multiple sclerosis (MS) patients were willing to bear the risk. Two cases of natalizumab-related PML (0.06‰) were confirmed in 32 000 patients without death report after two years of its remarketing, in July 2008. Another PML patient was reported in October 2008. Because of its non-substitutability for treating MS and Crohn disease (CD), FDA announced that patients could still use natalizumab under the close monitoring. Conclusion (1) The most serious adverse reaction of treating MS and CD with natalizumab is PML, but it can be preventable and curable now. The monitoring findings of efficacy and adverse reaction during the postmarketing indicate that the review system is perfect and practicable relatively, and can give references for other high-risk drugs on the fast or standard approval channel, for example, Chinese medicine injection can draw lessons from it. (2) The remarketing of natalizumab not only provide significant risk management precedent for other drug-development firms, but also brings hope to the remarketing or relaunching clinical trials for the suspected sideeffect drugs. (3) Because of the fast-track reviewing of natalizumab and the overlap between the research of Good Clinical Practice (GCP) and the post-marketing evaluation, we should continue to track the information and provide new evidence.
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.
Objective To compare and assess the efficacy of ventral/dorsal onlay graft urethroplasty in the treatment of urethral stricture. Methods We searched pertinent English literature via MEDLINE (1966 to 2007), EMBASE (1977 to 2007) and The Cochrane Library (Issue 4, 2007) for the use of ventral/dorsal graft urethroplasty in the reconstruction of urethral defect associated with urethral stricture. Data were extracted by two reviewers independently and analyzed by SPSS 13.0 software. Results A total of 50 studies involving 1 264 patients were included. Ventral onlay graft urethroplasty was used in 751 patients with a success rate of 82.6%, while dorsal onlay graft urethroplasty was used in 513 patients with a success rate of 86.9% (ventral vs. dorsal, χ2=4.432, P=0.035). Oral mucosa graft had the highest success rate (88.1%) of all grafts, and the success rate of free skin graft onlay urethroplasty was associated with the location of graft placement (ventral vs. dorsal, P=0.016). Concerning the location of stricture, urethroplasty for bulbar urethral stricture achieved the best results, with a success rate of 87.7%, which was also associated with the location of graft placement (ventral vs. dorsal, P=0.025). Conclusion Dorsal onlay graft urethroplasty is better than ventral onlay. It is better to place the free skin graft in the dorsal part of urethra. Bulbar urethral stricture is more suitable for graft onlay urethroplasty than penile urethral stricture.