Trial Sequential Analysis (TSA), one kind of cumulative meta-analysis, is a method which introduces sequential analysis into traditional meta-analysis to avoid random errors (false positive or false negative outcomes) that occurred during repeated updates when traditional meta-analysis is performing. It is also applied to calculate required information size (RIS) of a firm conclusion. This study aims to summarize the proposal, fundamental theory, application software, and current limitation of TSA, and to clarify the advantages of TSA on the basis of detailed examples, in order to attract more attention of researchers and promote the methodological development of meta-analysis in China.
摘要:目的:探讨有机磷农药中毒患者阿托品使用方法,提高抢救成功率。方法: 对2005年6月至2009年6月我院收治的有机磷农药中毒病人281例进行分组,所有患者均使用阿托品疗法,A组为2007年以后132例序贯阿托品疗法患者,B组2007年以前为常规使用静推继之肌注阿托品疗法149例患者,根据有机磷农药对胆碱酯酶复能剂的疗效分为高效组和低效组,并结合病情严重程度共分为重度有机磷农药中毒胆碱酯酶复能剂高效组、重度有机磷农药中毒胆碱酯酶复能剂低效组,轻度有机磷农药中毒胆碱酯酶复能剂高效组、轻度有机磷农药中毒胆碱酯酶复能剂低效组4组,分别从达到阿托品化时间、维持阿托品化效果、反跳和中间综合征发生率、开始撤药平均时间、总住院费用、总住院平均时间、护士劳动强度进行总结和分析。结果: 维持阿托品化疗效Ａ组与B组间有显著差异,P值lt;0.01,开始撤药平均时间、总住院平均时间、总住院费用、护士劳动强度Ａ组与B组间均有差异,P值lt;0.05,发生反跳和中间综合征发生率、达到阿托品化时间在高效组间比较无差异,低效组间比较无差异,高效组与低效组比较有显著差异,P值lt;0.01,主要与中毒药物种类和病情严重程度有关,其次与阿托品治疗方法有关。 结论: 序贯阿托品疗法治疗有机磷农药中毒优于常规使用静推继之肌注阿托品疗法。Abstract: Objective: To discussion of atropine in organophosphorus pesticide poisoning patients with the use of two different methods to improve the success rate. Methods: For June 2005 to June 2009 inour hospital a total of organophosphorus pesticide poisoning 281 cases were divided into A group and B group, All patients were using atropine therapy, 132 cases of sequential therapy in patients with atropine is divided into A group, 149 cases of routine use of intravenous injection and intramuscular injection of atropine group patients were divided into B group, From the following aspects were analyzed and summarized, They are the maintenance of the effect of atropinization, the average time for the beginning of withdrawal, the total hospitalization costs, the total average time for hospitalization and nurses labor intensity. According to the organic phosphorus pesticide on the efficacy of cholinesterase agents are divided into efficient and inefficient groups groups, From the types of poisons, toxic ways, poisoning performance and Complications for stratified, They were divided into 4 groups, severe organophosphorus pesticide poisoning and cholinesterase reactivator can be highly effective group, severe organophosphorus pesticide poisoning and cholinesterase reactivator Lowefficacy group, mild organophosphorus pesticide poisoning and cholinesterase reactivator can be highly effective group, mild organophosphorus pesticide poisoning and cholinesterase reactivator Lowefficacy group, Correlation analysis Antijumping and the incidence of intermediate syndrome and atropinization time.Results:Maintain the efficacy of atropine of A group and B were significantly different between groups, Plt;0.01, the average time began to withdraw drugs, the total average time for hospitalization, total hospital charges, nursing labor intensity of A group and B are differences between the two groups, P＜0.05. Rebound occurs and the incidence of intermediate syndrome, to atropinization time high between the two groups showed no difference between the two groups showed no differences between inefficient and efficient group and inefficient group were significantly different, Plt;0.01, mainly related to poisoning by drug type and severity of illness, followed with atropine therapy. Conclusion:Atropine sequential therapy is superior to organophosphorus pesticide poisoning by conventional atropine treatmen.
ObjectiveTo summarize the experience of 4 patients with a great saphenous venous graft patency after 15 years of postoperitive great saphenous venous sequential aortic coronary artery bypass grafting. MethodWe retrospectively analyzed the clinical data of 4 patients accepted great saphenous vein aortic coronary artery bypass graft under moderate hypothermia cardiopulmonary bypass from November 1989 to December 1992 year. There were 3 males and 1 female with a mean age of 48.3 years ranging from 40-58 years. We harvested great saphenous vein under groin 45-50 cm. The proximal and distal anastomoses were performed with parachute technique under two clamps technique. Coronary artery bypass graft was performed by two sequential grafts routinely. Aspirin was given through nasal tube 6 hours after operation. The risk factors of arteriosclerosis were controlled by patients themselves after discharge. ResultFour patients received coronary angiography in 15, 16, 18, and 21 years after surgery and the grafts and both proximal and distal anastomoses were patent. The patients lived about 20 years without angina. Conclusioncarefully dealing with the vein graft, taking sequential bypass grafting to guarantee parabolic curve and meticulous anastomosis are preconditional and necessary for long-term patency.
The robustness of results of statistical analysis would be altered on the condition of repeated update of traditional meta-analysis and cumulative meta-analysis. In addition, the cumulative meta-analysis lacks estimation of the sample size. While trail sequential analysis (TSA), which introduces group sequential analysis in meta-analysis, can adjust the random error and ultimately estimate the required sample size of the systematic review or meta-analysis. TSA is performed in TSA software. In the present study, we aimed to introduce how to use the TSA software for performing meta-analysis.
ObjectiveTo systematically evaluate the outcomes of drug-eluting balloon (DEB) in treating coronary artery in-stent restenosis (ISR) by using meta-analysis and trial sequential analysis (TSA). MethodsWe searched PubMed, EMbase, The Cochrane Library（Issue 4, 2016）, CNKI, CBM, VIP and WanFang Data to collect randomized controlled trials (RCTs) regarding the treatment of ISR by DEB from inception to April 2016. After two reviewers independently screened citations, extracted data and assessed the bias risk of included studies, we carried out meta-analysis and TSA analysis by using RevMan 5.3 version and TSA v0.9 respectively. ResultsA total of 10 RCTs involving 1909 patients were included. Seven-hundred and forty-seven patients were included with regard to the comparison between DEB and POBA, 1162 patients were recruited to compare DEB and drug-eluting stents (DES). The results of meta-analysis revealed that DEB was associated with decreased mortality (OR=0.36, 95%CI 0.14 to 0.93, P=0.04), compared with that of plain old balloon angioplasty (POBA). And TSA showed that cumulative Z-curve strode the conventional threshold value but not the TSA threshold value which suggested a false positive result of meta-analysis. In comparison with that of POBA, DEB had a lower incidence of target lesion revascularization (TLR) (OR=0.16, 95%CI 0.07 to 0.38, P＜0.01). And the result of TSA displayed that the cumulative Z-curve strode both the conventional and TSA threshold value which validated the result of meta-analysis. Besides, the results of meta-analysis showed that there were no significant differences in mortality (OR=0.84, 95%CI 0.41 to 1.72, P=0.63) and TLR (OR=1.55, 95%CI 0.76 to 3.16, P=0.22) between DEB and DES. However, the result of TSA revealed that the cumulative Z-curve did not strode both the conventional and TSA threshold value, and the included sample size less was than required information size which suggested that the reliability of the meta-analysis needed more studies to confirm. While the subgroup analysis of EES revealed that DEB had a higher incidence of TLR than that of DEB (OR=3.37, 95%CI 1.59 to 7.15, P＜0.01). And the result of TSA displayed that the cumulative Z-curve strode both the conventional and TSA threshold value which validated the result of meta-analysis. ConclusionCurrent evidence shows, EES is superior to DEB in decreasing the incidence of TLR in patients with ISR, while DEB is superior to POBA. However, the comparison of DEB and other strategies on reducing of mortality in patients with ISR still needed more studies to prove.
Cumulative meta-analysis could help researchers to justify the effectiveness of the intervention and whether the obtained evidence is sufficient. However, the process of the meta-analysis does not adjust the repeated testing of the null hypothesis and neither quantifies the statistical power. The sequential meta-analysis has solved the aforementioned problems and has been widely used in the clinical practice and decision-making. Currently several methods of sequential meta-analysis have been proposed and these methods differ from each other. Of which, the methodology of trial sequential (TSA) is well developed and corresponding performance is relatively easy; the methodology of double-triangular test of Whitehead is lagged than TSA and its performance is relatively difficult; the approach of semi-Bayes refers to the theory of Bayes and it's very difficult to generalize. Our paper aimed to give a brief introduction of the methodology of the sequential meta-analysis.
ObjectiveTo investigate the clinical value of quick sequential organ failure assessment (qSOFA) score in predicting the outcome of patients with septic shock. MethodsWe collected the clinical data of 170 patients with septic shock treated in the Emergency Intensive Care Unit between January 2013 and January 2014. According to the 28-day outcomes of the patients, they were recorded as survival group and non-survival group. We calculated the qSOFA score, acute physiology and chronic health evaluation (APACHE)Ⅱ score on patients' admission. Using receiver operating characteristic (ROC) curve, we analyzed the qSOFA score, the effect of APACHE Ⅱ score in predicting the 28-day prognosis for patients with septic shock. The correlation between qSOFA score and APACHEⅡ score was also assessed. ResultsThe qSOFA and APACHEⅡ scores in non-survivors were higher than those in the survivors. According to ROC curve analysis, the area under the curve for qSOFA score and APACHE Ⅱ score was 0.666 and 0.791, respectively. For qSOFA score with 2 cut-off points to evaluate the prognosis of septic shock, the sensitivity was 62.7%, specificity was 61.1%, positive predictive value was 56.0%, negative predictive value was 67.4%, positive likelihood ratio was 1.61, and negative likelihood ratio was 0.61. For the APACHEⅡ score with 24 cut-off points to evaluate the prognosis of septic shock, the sensitivity was 70.7%, specificity was 80%, positive predictive value was 73.6%, negative predictive value was 67.3%, positive likelihood ratio was 3.54, and negative likelihood ratio was 0.37. The correlation coefficient of qSOFA score and APACHE Ⅱ score was 0.499. ConclusionThe qSOFA score is useful to evaluate the prognosis of the patients with septic shock early in Emergency Department.
ObjectiveTo systematically review the association between angiotension-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and osteoarthritis (OA) by using meta-analysis and trial sequential analysis (TSA). MethodsThe PubMed, EMbase, CNKI, CBM, VIP, and WanFang Data were searched up to October 12th, 2016 for case-control or cohort studies on the correlation between ACE I/D polymorphism and OA risk. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis and TSA analysis were performed using Stata 13.1 software and TSA v0.9 soft ware. ResultsA total of six case-control studies involving 1 165 OA patients and 1 029 controls were included. The results of meta-analysis showed that the ACE I/D was associated with OA risk (DD+DI vs. II: OR=1.72, 95%CI 1.02 to 2.90, P=0.04; DI vs. II: OR=1.65, 95%CI 1.06 to 2.56, P=0.03). Subgroup analysis of ethnicity showed that, in Caucasians, the ACE I/D was associated with OA risk (DD vs. DI+II: OR=2.10, 95%CI 1.54 to 2.85, P<0.01; DD+DI vs. II: OR=3.11, 95%CI 2.20 to 4.39, P<0.01; DD vs. II: OR=4.01, 95%CI 2.68 to 6.00, P<0.01; DI vs. II: OR=2.65, 95%CI 1.06 to 2.56, P<0.01; D vs. I: OR=2.11, 95%CI 1.72 to 2.58, P=0.73). And TSA showed that all of the cumulative Z-curve strode the conventional and TSA threshold value which suggested the result of the association between ACE I/D polymorphism and OA in Caucasians was very reliable. However, the association did not exist in Asians (DD vs. DI+II: OR=0.80, 95%CI 0.60 to 1.07, P=0.13; DD+DI vs. II: OR=1.08, 95%CI 0.87 to 1.35, P=0.49; DD vs. II: OR=0.86, 95%CI 0.62 to 1.20, P=0.38; DI vs. II: OR=1.18, 95%CI 0.93 to 1.50, P=0.19; D vs. I: OR=0.93, 95%CI 0.83 to 1.14, P=0.73). And the results of TSA displayed that all of the cumulative Z-curve did not strode both TSA threshold value and required information size line excepting for DD vs. DI+II genetic model which suggested that the sample-size in Asians was insufficient. ConclusionsThe ACE D allele maybe a risk factor for OA in Caucasians. However, the association between ACE I/D polymorphism and OA risk in Asians still need more studies to prove.
Trial sequential analysis (TSA) could be performed in both TSA software and Stata software. The implementation process of TSA in Stata needs the command of "metacumbounds" of Stata combines with the packages of "foreign" and "ldbounds" of R software. This paper briefly introduces how to implement TSA using Stata software.
Trial sequential analysis (TSA) can identify inclusive results of apparently conclusive of meta-analyses by providing require information size and monitoring boundary. Certain methods of calculating information size are existed. Our objective was to give a brief introduction of four methods to help readers to better perform TSA in making meta-analyses.