Objective To evaluate the curative effectiveness and safety of prophylactic chemohyperthermic peritoneal perfusion (CHPP) during the radical surgery of advancing gastric cancer. Methods We searched MEDLINE (1980 to December 2002), EMBASE (1989 to December 2002), BIOSIS Previews (1980 to December 2002), Cochrane Controlled Trials Register (Issue 4, 2003) and CBMdisc (1981 to December 2002). Randomized or quasi-randomized controlled trials comparing curative gastrectomy (CG) plus CHPP with CG for advancing gastric cancer were collected. The methodological quality of included studies was assessed, and a meta-analysis was performed by RevMan 4.2 software. Results Seven RCTs involving 744 patients met the selection criteria, all trials were of lower methodological quality. ① Meta-analysis results showed that no significant difference was found comparing CG plus CDDP (cisplatin) with CG for peritoneal recurrence after operation (The pooled OR 0.69，95%CI 0.43 to 1.12). Compared with CG alone, CG plus CDDP plus MMC significantly reduced peritoneal recurrence after operation during ≥5 years follow up (OR 0.05, 95% CI 0.01 to 0.37), but this effect was not seen during lt; 5 years follow up (OR 0.35，95%CI 0.06 to 2.10). ② CG plus CDDP significantly reduced mortality after operation during ＜5 and ≥5 years follow up, compared with CG alone (OR 0.25, 95%CI 0.08 to 0.75; the pooled OR 0.62, 95%CI 0.41 to 0.95), CG plus CDDP plus MMC significantly reduced mortality after operation during ≥5 years follow up, compared with CG alone (the pooled OR 0.45, 95%CI 0.28 to 0.74), but this effect was not seen during lt; 5 years follow up (OR 0.29, 95%CI 0.08 to 1.15). ③ Side effects were reported in only one study and no significant difference was found between the two groups (P=0.96). Conclusions Because of the small number of included studies, the lower methodological quality, and the differences in diagnostic criteria of peritoneal recurrence after operation, the reviewers feel that no firm conclusion could be drawn. Some well designed RCTs of CHPP for advancing gastric cancer should be undertaken to further evaluate its effectiveness.
Objective To discuss the methods of producing experimental models of chronic pancreatitis and their individual properties. Methods The recent literatures about experimental models of chronic pancreatitis were reviewed and analyzed. Methods of producing experimental models and their individual properties were summarized, and best models suitable for varied chronic pancreatitis were afforded. Results Diet, ligation of pancreatic duct, caerulein, dibutyltin dichloride (DBTC), arterial ligation, injecting microspheres into artery, and injection of pancreatic duct could induce different experimental models of chronic pancreatitis. Spontaneous chronic pancreatitis was induced by diet, chronic obstructive pancreatitis produced by ligation and injection of pancreatic duct, chronic relapsing pancreatitis evoked by caerulein, and chronic active pancreatitis made by arterial ligation and injecting microspheres into artery.Conclusion Different methods could induce models of chronic pancreatitis, which had their individual properties.
Objective To investigate whether the growth of the human experimental hepatocellular carcinoma (HCC) can be suppressed by the antibody against vascular endothelial growth factor (VEGF). MethodsThe monoclonal antiVEGF antibody was injected to nude mice nearby the xenograft tumour foculs of the human SMMC7721 HCC. The changes of the tumour size were measured at different times. The intratumoural microvessels were showed by immunohistochemical staining of CD31 antigen; the apoptotic cells in the tumour tissues were detected in situ by terminal deoxynucleotidyl transferasemediated dUTPbiotin nick end labeling (TUNEL) assay. ResultsIn the first and second week after finishing the injection procedure, the tumour sizes were compared as the length (mm) multiplying width (mm) between the two groups, the tumour sizes as the test group vs the control group were (26.46±19.81) mm2 vs (105.77±17.40) mm2 (P＜0.001) and (45.20±23.02) mm2 vs (150.77±77.41) mm2 (P＜0.05), respectively. After 2 weeks the intratumoural microvessel density (iMVD) and the apoptotic index (AI) were compared between two groups with iMVD being (2 311±120)/mm2 vs (3 900±328)/mm2(P＜0.001 ) and AI being (15.31% vs 6.83%), P＜0.005. Conclusion The antiVEGF antibody can suppress the xenograft tumour growth of the human SMMC7721 HCC by antiangiogenesis.In fact, its antitumour effect is produced by elevating the incidence of apoptosis in tumour tissues.
Randomized controlled trials (RCTs) are currently the gold standard for the treatment effect comparisons; however, it is sometimes not feasible to conduct an RCT due to ethical and economic reasons. In the absence of evidence for head-to-head RCT direct comparison, the indirect comparison technique is an effective and resource-saving alternative. Matching-adjusted indirect comparison (MAIC) is an attractive method in the field of population-adjusted indirect comparisons between two trials. It can adjust for between-trial imbalances in the distribution of observed covariates by weighting the available individual patient data of the studied intervention and then match the aggregated data of the controlled intervention. Subsequently, the treatment effect comparison can be evaluated through the post-matched population. Although MAIC is gaining increasing attention in clinical research, especially in the evaluation of new drugs, efforts are still largely required for knowledge dissemination in China. In this paper, we briefly introduced the concepts, research value and examples, and pros and cons of MAIC.
Objective To investigate the effectiveness of posterior non-decompression surgery in the treatment of thoracolumbar fractures without neurological symptoms by comparing with the conventional posterior decompression surgery. Methods Between October 2008 and October 2015, a total of 97 patients with thoracolumbar fractures with intraspinal occupying 1/3-1/2 and without neurological symptoms were divided into the decompression surgery group (51 cases) and the non-decompression surgery group (46 cases). There was no significant difference in gender, age, cause of injury, injury segment, the thoracolumbar injury severity score (TLICS), combined injury, disease duration, and preoperative relative anterior vertebral height, kyphosis Cobb angle, intraspinal occupying percentage, visual analogue scale (VAS), Oswestry disability index (ODI), and Japanese Orthopaedic Association (JOA) score between 2 groups (P>0.05). The operation time, intraoperative blood loss volume, postoperative drainage, bed rest time, hospitalization time, and relative anterior vertebral height, kyphosis Cobb angle, intraspinal occupying percentage, and VAS score, ODI, JOA score at preoperative and postoperative 3 days and 1 year were recorded and compared. Results The operation time, intraoperative blood loss volume, and postoperative drainage in non-decompression surgery group were significantly less than those in decompression surgery group (P<0.05). There was no significant difference in the postoperative bed rest time and hospitalization time between 2 groups (P>0.05). In decompression surgery group, 4 cases had cerebrospinal fluid leakage and healed after conservative treatment. All incisions healed by first intention, and no nerve injury or infection of incision occurred. All patients were followed up 10-18 months (mean, 11.7 months). The recovery of vertebral body height was satisfactory in 2 groups, without secondary kyphosis and secondary nerve symptoms. The imaging indexes and effectiveness scores of 2 groups at 3 days and 1 year after operation were significantly improved when compared with preoperative ones (P<0.05). The intraspinal occupying percentage, VAS score, and ODI at 1 year after operation were significantly lower than those at 3 days after operation in 2 groups (P<0.05), and JOA score at 1 year after operation was significantly higher than that at 3 days after operation (P<0.05). Relative anterior vertebral height at 1 year after operation was significantly higher than that at 3 days after operation in non-decompression surgery group (P<0.05); and there was no significant difference in decompression surgery group (P>0.05). At 3 days, the intraspinal occupying percentage and JOA score in non-decompression surgery group were higher than those in decompression surgery group (P<0.05), and VAS score and ODI at 3 days in non-decompression surgery group were lower than those in decompression surgery group (P<0.05). No significant difference was found in the other indexes between 2 groups at 3 days and 1 year after operation (P>0.05). Conclusion Compared with the posterior decompression surgery, posterior non-decompression surgery has the advantages of less bleeding, less trauma, less postoperative pain, and so on. It is an ideal choice for the treatment of thoracolumbar fractures with intraspinal occupying 1/3-1/2 and without neurological symptoms under the condition of strict indication of operation.
Propensity score methods belong to an analytical approach by incorporating the measured covariates and mimicking randomization to enhance the comparability between groups, hence reducing the impact of potential confounding in observational studies. Propensity score methods have been increasingly used in observational studies. This paper illustrates the principle and the methods based on the propensity score, in combination with its application in observational studies. It also compares results from propensity score methods with those from multivariable regression and randomized controlled trials. It was found that currently there has been a lack of recommendations for the selection of propensity score methods. Differences may exist when comparing results from propensity score methods with findings from typical regression analyses and randomized controlled trials.
In medical research, pilot and feasibility studies are conducted to reduce the uncertainty of future main trial and enhance its overall quality and probability of successful completion. The objective of a pilot and feasibility study is to answer whether the main trial can be performed, should be performed, and if so, how. Due to the tremendous resources, time, and funding required for a phase Ⅲ clinical trial, conducting a pilot and feasibility study is generally a pivotal step. While pilot and feasibility studies are gaining increasing attention in clinical research, efforts are largely required to promote the dissemination in China. Therefore, in this article, we briefly introduce the concepts of a pilot and feasibility study, its importance to the main trial, and current practice. Examples are also provided to help illustrate the introduction.
A patient registry database is an important source of real-world data, and has been widely used in the assessment of drug and medical devices, as well as disease management. As the second part of the serial technical guidance for real-world data and studies, this paper introduces the concept and scope of potential uses of patient registry databases, proposes recommendations for planning and developing a patient registry database, and compares existing health and medical databases. This paper further develops essential quality indicators for developing a patient registry database, in expect to guide future studies.
Assessing the clinical value of pharmaceuticals is crucial for comprehensive evaluation in clinical practice and plays a vital role in supporting decision-making for drug supply assurance. Real-world data (RWD) offers valuable insights into the actual diagnosis and treatment processes, serving as a significant data source for evaluating the clinical demand, effectiveness, and safety of drugs. This technical guidance aims to elucidate the scope of application of RWD for the clinical value assessment of pharmaceuticals, as well as the key considerations for conducting value assessment research. These considerations include identifying the dimensions of clinical value that necessitate RWD and effectively utilizing RWD for evaluation purposes. Additionally, this guidance provides essential points for implementing pharmaceutical clinical value assessment based on real-world data, with a specific focus on study design and statistical analysis. By doing so, this guidance assists researchers in accurately comprehending and standardizing the utilization of real-world research in conducting pharmaceutical clinical research.
In the clinical evidence-based decision-making process, factors including benefits and harms, evidence certainty, cost and feasibility of interventions should be considered based on the best evidence. The development of decision threshold of effect size (DTES) for patient health outcomes can help stakeholders understand the benefits and harms of interventions, assess evidence certainty, and interpret research results. Based on international experience, the MERGE Working Group through group discussions, semi-structured interviews, expert consensus, and pilot application developed a set of 8-step guidelines for the development of DTES for health outcomes. These steps included necessity assessment, formation of working groups, selection of patient important outcomes, creation of scenarios based on the best evidence, design of expert consultation questionnaires, analysis of expert consultation results, face-to-face expert consensus, dissemination of the application and reevaluation. The DTES guideline development is intended to provide methodological guidance for stakeholders to develop DTES for health outcome indicators in different domains.