Cost-effectiveness analysis of serplulimab combined with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of serplulimab combined with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma from the perspective of the Chinese healthcare system. METHODS A partitioned survival model with three health states was constructed for cost-effectiveness analysis. Clinical data were extracted from ASTRUM- 007. Information on parameters such as cost and health utility was derived from related websites and published literature. The quality-adjusted life years （QALYs） was used as the output index to calculate the incremental cost-effectiveness ratio （ICER）， and then compared with three times the per capita gross domestic product （GDP） in China to judge whether it was cost-effective. One- way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model； the cost- effectiveness of applying this plan to subgroup patients with programmed cell death-ligand 1 combined positive score （PD-L1 CPS） ≥10 and the scheme in the context of charitable drug donations was explored. RESULTS Among advanced or metastatic oesophageal squamous cell carcinoma patients and patients with PD-L1 CPS ≥10， serplulimab combined with chemotherapy could improve health outcomes with an augmentation of cost， compared with placebo combined with chemotherapy，resulting the ICERs were 599 623.64 yuan/QALY and 629 121.57 yuan/QALY， respectively. Therefore， serplulimab combined with chemotherapy was not cost-effective. Sensitivity analysis of single factor showed that the costs of serplulimab were the crucial factor affecting the ICER； probabilistic sensitivity analysis demonstrated basic analysis results were relatively robust. The results of scenario analysis showed that when all patients met the requirements of the charitable drug donation program， serplulimab combined with chemotherapy was cost-effective； the economic outcome of this scheme was reversed compared with the results of the basic analysis. CONCLUSIONS From Chinese healthcare perspective， first-line treatment with serplulimab in combination with chemotherapy is not a cost-effective option for patients with advanced esophageal squamous cell carcinoma， but it may be an economic option to implement a charitable drug donation program for all patients or if the price of serplulimab is significantly reduced.

Efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit / 中华神经科杂志

Objective:To confirm the efficacy and safety of cinepazide maleate injection in acute ischemic stroke patients with obvious motor function deficit.Methods:This study is a subgroup analysis of multi-center, randomized, double-blind, placebo-controlled phase Ⅳ clinical trial. A total 812 patients of acute ischemic stroke with obvious limb motor deficit [motor function of limbs score in National Institutes of Health Stroke Scale (NIHSS) ≥4] were enrolled in this subgroup analysis. Patients received either cinepazide maleate injection or placebo. The treatment period was 14 days and follow-up was 90 days. The efficacy endpoints included the proportions of patients with a modified Rankin Scale (mRS) score ≤2, mRS score ≤1 and Barthel Index <95 on day 90. Safety was evaluated by recording all adverse events, monitoring vital signs, laboratory parameters and electrocardiogram.Results:A total of 732 patients were involved in the final efficacy analysis (361 in cinepazide maleate group and 371 in control group). The baseline limb motor function score of NIHSS was 5.23±1.43 in the cinepazide maleate group whereas 5.20±1.36 in the control group. Logistic regression analysis showed that following treatment for 90 days, the proportion of patients with a mRS score ≤2 was significantly higher in the cinepazide maleate group than in the control group [56.0% (202/361) vs 44.2% (164/371), OR=0.60, 95% CI 0.44-0.82, P=0.002]. The proportion of patients with a mRS score ≤1 was higher in the cinepazide maleate group than in the control group [43.3% (139/361) vs 35.2% (118/371), OR=0.69, 95% CI 0.50-0.97, P=0.031]. The proportion of patients with a Barthel Index <95 on day 90 was significantly lower in the cinepazide maleate group than in the control group [45.2% (145/361) vs 55.2% (185/371), OR=0.64, 95% CI 0.46-0.88, P=0.007]. During the treatment and follow-up period, the incidence of the most common adverse events in the cinepazide maleate group was 50.4% (199/395). Constipation and abnormal liver function were more common, but there were no statistically significant differences between the two groups. Conclusion:Cinepazide maleate injection is superior to placebo in improving neurological function and activities of daily living, reducing disability, and promoting functional recovery and safe in patients with acute ischemic stroke with obvious limb motor deficit.

Bidirectional regulation of acupuncture: a subgroup analysis of multicenter randomized controlled trial of acupuncture with / 中国针灸

OBJECTIVE@#To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture with @*METHODS@#A total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up.@*RESULTS@#The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (@*CONCLUSION@#Acupuncture with

Prognostic and subgroup analysis of 162 patients with Barcelona Clinical Liver Cancer (BCLC)stage B hepatocellular carcinoma after hepatectomy / 中华肝胆外科杂志

Objectives To analyze prognosis and risk factors of Barcelona Clinical Liver Cancer (BCLC) stage B hepatocellular carcinoma patients treated with hepatectomy.Methods Clinical data of 162 BCLC stage B patients who underwent hepatectomy at Tianjin Medical University Cancer Institute & Hospital and the Second Hospital of Tianjin Medical University from June 2007 to December 2013 were retrospectively studied.The correlations between factors (age,gender) and long-term outcome were analyzed to determine independent risk factors.Subsequently,subgroup analysis of BCLC stage B hepatocellular carcinoma was performed.Results Multiple tumors,maximum tumor diameter ＞ 10 cm and AFP ＞ 100 μg/L were con firmed as independent risk factors of overall survival in postoperative BCLC B patients.Based on the risk factors,patients were divided into two groups,namely low-risk subgroup (≤ 1 risk factor) and high-risk subgroup (≥ 2 risk factors).In low-risk subgroup,1,3 and 5-year overall survival (OS) rates were 91.6％,65.5％,61.9％ respectively,and mean OS was 72 months.By contrast,1,3 and 5-year OS rates in high-risk subgroup were 67.4％,25.6％,10.8％ respectively,and mean OS was 29 months.Further more,1,3 and 5-year OS rates of all patients were 85.2％,54.9％,48.0％ respectively,and mean OS was 61 months.Conclusions Relatively favorable long-term outcomes could be yielded in BCLC stage B hepatocellular carcinoma patients treated with liver resection.The independent risk factors including multiple tumors,maximum tumor diameter ＞ 10 cm and AFP ＞ 100 μg/L were closely correlated with overall survival.BCLC stage B hepatocellular carcinoma patients could be divided into low-risk and high-risk subgroups based on the risk factors mentioned above.Survival rates in low-risk subgroup are remarkably superior to those in high-risk subgroup.

Meta-analysis on incidence of adverse drug reaction induced by Shuanghuanglian injection / 中国中药杂志

To conducted a systematic review on the safety of Shuanghuanglian injection in clinical use. In this paper, data from Pubmed, Embase, the Cochrane Library, CNKI, VIP and WanFang Data were retrieved. After extracting information and evaluating research methodological quality according to inclusion and exclusion criteria, Meta-analysis was conducted by using R3.2.3 software. A total of 56 individual studies were included, in which 585 cases showed adverse reactions in a total of 11 001 patients with Shuanghuanglian injections. Meta-analysis showed that the total incidence of adverse reactions was 6.5% (95%CI 0.051 to 0.082). Subgroup analysis showed that the incidence of adverse reactions was 4.8% (95%CI (0.032 to 0.067) and 8.1% (95%CI 0.054 to 0.112) respectively in children and adults; 7.2% (95%CI 0.049 to 0.095) and 6.6% (95%CI 0.036 to 0.104) respectively in 5%-10% glucose injection and 0.9% sodium chloride injection; 6.3% (95%CI 0.047 to 0.082) and 7.0% (95%CI 0.044 to 0.099) respectively in powder injection and liquid injection; 5.8% (95%CI 0.043 to 0.075) and 8.9% (95%CI 0.049 to 0.140) respectively in cases with duration of ≤7 d and >7 d; 4.2%(95%CI 0.027 to 0.059) and 8.4% (95%CI 0.059 to 0.113) respectively in single use and combined medication. Three most frequent types of adverse reaction symptoms reported were in skin and mucosa, digestive system, and body temperature center, with an incidence of 4% (95%CI 0.03 to 0.04), 3% (95%CI 0.02 to 0.03), and 1% (95%CI 0.00 to 0.01), respectively. The systemic evaluation demonstrated that the occurrence of adverse reaction of Shuanghuanglian injection was related to age, menstruum, duration of medication and combined medication. Incidence of adverse reactions differed considerably among different damage types. From the study demonstrated above, this paper concludes that we should follow the principles of evidence-based medication of traditional Chinese medicine; use Shuanghuanglian injection singly instead of combination with other drugs in clinical use; use Shuanghuanglian injection strictly in accordance to instructions, especially for children and the elderly, whose weight should be calculated and considered in medication; intensively monitor the drug adverse reaction after use; assess the risks of adverse effects for long-term usage, and take corresponding safety measures to ensure safety.

Statistical issues in randomised controlled trials: A narrative synthesis

ABSTRACT: Randomised controlled trials (RCT s) are gold standard in the evaluation of treatment efficacy in medical investigations, only if well designed and implemented. Till date, distorted views and misapplications of statistical procedures involved in RCTs are still in practice. Hence, clarification of concepts and acceptable practices related to certain statistical issues involved in the design, conduct and reporting of randomised controlled trials is needed. This narrative synthesis aimed at providing succinct but clear information on the concepts and practices of selected statistical issues in RCT s to inform correct applications. The use of tests of significance is no longer acceptable as means to compare baseline similarity between treatment groups and in determining which covariate(s) should be included in the model for adjustment. Distribution of baseline attributes simply presented in tabular form is however, rather preferred. Regarding covariate selection, such approach that makes use of information on the degree of correlation between the covariate(s) and the outcome variable is more in tandem with statistical principle(s) than that based on tests of significance. Stratification and minimisation are not alternatives to covariate adjusted analysis; in fact they establish the need for one. Intention-to-treat is the preferred approach for the evaluation of primary outcome measures and researchers have responsibility to report whether or not the procedure was followed. A major use of results from subgroup analysis is to generate hypothesis for future clinical trials. Since RCT s are gold standard in the comparison of medical interventions, researchers cannot afford the practices of distorted allocation or statistical procedures in this all important experimental design method.

Helicobacter pylori Seropositivity Is Associated with Gastric Cancer Regardless of Tumor Subtype in Korea

BACKGROUND/AIMS: To evaluate the association between Helicobacter pylori (H. pylori) infection and gastric cancer (GC) according to tumor subtype in Korea. METHODS: H. pylori status was determined serologically using the enzyme-linked immunosorbent assay. In total, 2,819 patients with GC and 562 healthy controls were studied. A logistic regression method was used after adjusting for possible confounders. RESULTS: The prevalence of H. pylori infection was significantly higher in the GC patients (84.7%) than in the controls (66.7%) (odds ratio [OR], 3.13; 95% confidence interval [CI], 2.46-3.97). The adjusted OR was significantly higher in H. pylori-infected patients aged or =60 years (OR, 1.48; 95% CI, 0.88-2.46; p<0.001). Subgroup analyses revealed no differences in seroprevalence between early gastric cancer (84.8%; OR, 3.01; 95% CI, 2.27-4.01) and advanced gastric cancer (84.6%; OR, 2.94; 95% CI, 2.24-3.85), cardia cancer (83.8%; OR, 2.98; 95% CI, 2.16-4.02) and noncardia cancer (84.8%; OR, 3.17; 95% CI, 2.48-4.04), and differentiated carcinoma (82.7%; OR, 2.99; 95% CI, 2.21-4.04) and undifferentiated carcinoma (86.8%; OR, 3.05; 95% CI, 2.32-4.00). CONCLUSIONS: The seroprevalence of H. pylori was higher in GC patients than in healthy controls, especially in younger patients. H. pylori infection is associated with GC, regardless of the tumor location, stage, or differentiation.

Subgroup Analysis in Meta-Analysis: a comparison of different methods / 薬剤疫学

<b>Introduction</b> : Meta-analysis is well recognized as the most important study methodology in pharmacoepidemiology. The cause of heterogeneity of the effects among studies in the conventional meta-analyses, has been typically analyzed by meta-regression and sometimes by extracting several studies in a post hoc manner, constructing subgroups from these studies and analyzing the effect in this subgroup. However, if multiple study subgroups are produced in a post hoc manner, since the potential possible number of subgroups is very huge, the multiplicity of testing results in the inflation of the type I error rate. Therefore, even when a significant subgroup has been identified, it can represent a type I error, due to multiplicity of testing. To insist on the significance of a post hoc subgroup analysis, it is indispensable to conduct an analysis adjusted for multiplicity.<br><b>Objective</b> : The present study was undertaken to establish a method for resolving the problem for the multiplicity of subgroup analysis in meta-analysis.<br><b>Methods</b> : Performance comparisons among the Bonferroni method, the Holm method, the Scheffe type method and the closed testing procedure were conducted, assuming the actual meta-analysis of clinical studies on colon cancer.<br><b>Results</b> : In the subgroup analysis without adjustment for multiplicity, the probability of type I error was unacceptably high. On the other hand, the four methods mentioned above can control this probability to below the nominal significance level. Under many situations, the closed testing procedure showed a relatively higher power, and this method was particularly superior to the other methods when a relatively high percentage of studies revealed minor effects.

A Review Study on Comparing Treatment Effects among Subgroups / 한국역학회지

It is interested in examining treatment effect on a particular category of subjects or in comparing treatment effects among different subgroups as well as overall treatment effect due to heterogeneity of study subjects. Subgroup analyses are exceedingly common, but they are also often misleading. Conclusions based on subgroup analyses can do harm both when a particular category of people is denied effective treatment (a "false-negative" conclusion), and when ineffective or even harmful treatment is given to a subgroup of people (a "false-positive" conclusion). Because of the frequency and the importance of clinical application of subgroup analysis, researchers need to be cautious about doing subgroup analyses. This study presents guidelines to help conducting subgroup analyses correctly.