1.Feasibility study of using clinical trial individual-level data sample bank as external control to support drug and device development:taking transcatheter aortic valve replacement device as an example
Xiao-ying LIN ; Chi-lie DANZENG ; Duo-er WANG ; Ying-xuan ZHU ; Ye LU ; Fan GAO ; Yuan-xin LI ; Meng-zhu SU ; Zi-long ZHANG ; Min CHEN ; Qi-ze LI ; Ru JIANG ; Yan-yan ZHAO ; Yang WANG
Chinese Journal of Interventional Cardiology 2025;33(8):459-466
Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.
2.Feasibility study of using clinical trial individual-level data sample bank as external control to support drug and device development:taking transcatheter aortic valve replacement device as an example
Xiao-ying LIN ; Chi-lie DANZENG ; Duo-er WANG ; Ying-xuan ZHU ; Ye LU ; Fan GAO ; Yuan-xin LI ; Meng-zhu SU ; Zi-long ZHANG ; Min CHEN ; Qi-ze LI ; Ru JIANG ; Yan-yan ZHAO ; Yang WANG
Chinese Journal of Interventional Cardiology 2025;33(8):459-466
Objective To explore the feasibility and corresponding implementation methods of constructing a sample resource bank based on individual-level data of completed clinical trials and using it to construct external controls for drug/device clinical trials.Methods Taking the pre-marketing clinical trial of transcatheter active valve replacement(TAVR)for the treatment of aortic valve stenosis as an example,the individual-level databases of multiple trials were standardized to form a sample bank.The original data of any trial in the sample bank were selected as the experimental group,and the remaining samples were selected as the control group.The potential confounding was handled by using the propensity score matching and stratification methods to clarify the process of constructing external controls based on the sample bank of individual-level data of clinical trials.Results This study included individual-level data of single-group trials of 4 TAVR devices,with a total of 569 subjects(59.2%male).The number of subjects in Trials 1 to 4 was 120,120,163,and 166,respectively.Propensity score matching enabled the matching of 113,117,125,and 147 subjects with comparable or similar characteristics from individual-level data from other trials,respectively,demonstrating a high matching success rate.The PS score distribution plot after stratification showed that the proportions of subjects in the experimental and control groups in strata 1 to 5 in scheme 1 were 4/103,11/103,22/92,32/87,and 51/64,respectively.For all constructed external controlled trials,a certain number of control samples with similar baseline characteristics to the experimental groups were distributed within each propensity score stratum.The results of the simulation test also reflected the potential differences between different devices in the 12-month all-cause mortality rate.Conclusions The sample bank constructed with individual-level data from clinical trials,as a high-quality data source,can serve as a source of external control for single-arm trials in the same field,and as a useful supplement to the external control scenario of real-world evidence to support drug and device development.At the same time,targeted research on research methods and bias control measures in related fields is also needed.
3.The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis.
Tao WU ; Yao Wei ZOU ; Jian Da MA ; Chu Tao CHEN ; Xue Pei ZHANG ; Jian Zi LIN ; Yan Hui XU ; Kui Min YANG ; Qian ZHANG ; Yao Yao ZOU ; Ying Qian MO ; Lie DAI
Chinese Journal of Preventive Medicine 2022;56(5):574-582
Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.
Adolescent
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Adult
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Aged
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Arthritis, Rheumatoid/epidemiology*
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Cholesterol, LDL
;
Cross-Sectional Studies
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Female
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Humans
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Male
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Middle Aged
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Non-alcoholic Fatty Liver Disease/epidemiology*
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Obesity/epidemiology*
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Overweight/epidemiology*
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Triglycerides
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Young Adult
4.Trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai from 1993 to 2017
Yan-min WANG ; Jian-jing XIONG ; Wen-jun GAO ; Xiao-lie YIN ; Xiao-ming YANG ; Guang-wen CAO
Shanghai Journal of Preventive Medicine 2021;33(10):905-912
Objective:To characterize the trends in the incidence and mortality of colorectal cancer in Jing'an District of Shanghai, thus optimizing the prophylactic options for this malignancy. Methods:Data from Shanghai Cancer Registration and Reporting System were used to analyze the colorectal cancer prevalence in Jing'an District from 1993 to 2017. Joinpoint software was used to analyze the trends in the standardized incidence rate and mortality rate by calculating the annual percentage of change (APC) and the average annual percentage of change (AAPC). Results:A total of 13 580 new cases of colorectal cancer were reported in Jing'an District during 1993 and 2017, with an average crude incidence rate of 52.94/105 and a standardized incidence rate of 24.77/105. The total number of deaths was 7 572, with an average crude mortality rate of 29.52/105 and a standardized mortality rate of 12.20/105. The standardized incidence rate of colorectal cancer in Jing'an District from 1993 to 2017 showed an increasing trend (AAPC=1.64%,
5.Effect and Mechanism of Traditional Chinese Medicine on Prevention and Treatment of Pathological Scar
Zi-li SUN ; Si-yu LIU ; Ming-li ZOU ; Yi FENG ; Yong DU ; Min-lie YANG ; Shun YU ; Zheng-dong YUAN ; Jun-jie WU ; Guo-zhong LYU ; Feng-lai YUAN
Chinese Journal of Experimental Traditional Medical Formulae 2020;26(17):225-234
Pathological scar is a kind of skin fibrotic disease caused by abnormal wound healing, including hypertrophic scar and keloid. Pathological scar may lead to aesthetic flaws, limb dysfunction and local discomfort in patients. Due to the complexity of the wound healing process, the formation of scar is affected by many factors. In addition to traditional surgical, laser, cryostatic and hormone injection methods for the treatment of pathological scar, there are new therapies, such as mesenchymal stem cell therapy, fat transplantation, interferon, and botulinum toxin. They are widely used in clinical practice, but with such problems as high prices and many side effect. Traditional Chinese medicine (TCM) has a long history in treating pathological scar. In recent years,
6.The Effect of Serum Cytokine Levels prior Transplantation on the Outcome of Severe Aplastic Anemia Patients Received Allogeneic Hematopoietic Stem Cell Transplantation.
Zhao WANG ; Yuan-Yuan SHI ; Xin YANG ; Su-Dong ZHANG ; Li-Ning ZHANG ; Dong-Lin YANG ; Yi HE ; Rong-Li ZHANG ; Er-Lie JIANG ; Jia-Lin WEI ; Si-Zhou FENG ; Min-Zhe HAN
Journal of Experimental Hematology 2018;26(2):502-507
OBJECTIVETo identify the role of serum cytokine levels prior allogeneic hematopoietic stem cell trans-plantation (allo-HSCT) in the outcome of severe aplastic anemia (SAA) patients received allo-HSCT treatment.
METHODSThe clinical data of 117 SAA patients received allo-HSCT were enrolled in this study. The overall survival (OS), graft versus host disease (GVHD) incidence and relationship of serum cytokines with OS and major transplantation complications were retrospectively analyzed.
RESULTSThe patients enrolled in this study included 78(66.7%) cases received HSCT matched sibling donors (MSD), 12(10.2%) HSCT of unrelated donors (MUD) and 27 cases received HSCT of haploidentical donors (HID). The 5-years OS was 76.0%(95% CI: 64.4-87.5%); aGVHD cumulative incidence was 49.6%(95% CI: 40.4%-58.8%) and cumulative incidence cGVHD was 31.6%(95% CI:23.1%-40.2%). MSD allo-HSCT had a significantly higher 5-years OS as compared with the other donors(82.3%±6.6% vs 61.3%±11.7%, P<0.05). HLA matching, donor's age, cytomegalovirus/ Epstein-Barr virus (CMV/EBV) infection were important factors of affecting occurence of aGVHD. The patients with higher serum IL-6 had reduced platelet recovery time after transplantation (14.6±1.8 vs 18.3±2.6 d)(P=0.050) and higher serum TNF-α level accompanied by a lower incidence of CMV/EBV infection (37.8%±11.1% vs 58.8±16.8%)(P<0.05).
CONCLUSIONMSD allo-HSCT is the effective treatment for SAA patients. Donor's type remains the strong predictor of survival. The serum levels IL-6 and TNF-α before transplantation associate with platelet recovery and CMV/EBV infection.
Anemia, Aplastic ; Cytokines ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Retrospective Studies ; Treatment Outcome
7.Continuous Use of Thienopyridine May Be as Safe as Low-Dose Aspirin in Endoscopic Resection of Gastric Tumors.
Sooyeon OH ; Sang Gyun KIM ; Jung KIM ; Ji Min CHOI ; Joo Hyun LIM ; Hyo Joon YANG ; Jae Yong PARK ; Seung Jun HAN ; Jue Lie KIM ; Hyunsoo CHUNG ; Hyun Chae JUNG
Gut and Liver 2018;12(4):393-401
BACKGROUND/AIMS: Current guidelines recommend withholding antiplatelets for 5–7 days before high-risk endoscopic procedures. We investigated whether this reduces post-endoscopic submucosal dissection (ESD) bleeding. METHODS: Gastric ESD cases with antiplatelets were retorospectively reviewed. Withholding antiplatelets for 5–7 days before ESD was defined as cessation and 0–4 days as continuation. The rate and risk of post-ESD bleeding according to the types and cessation of antiplatelets were assessed. RESULTS: Among the 215 patients (117 adenoma and 98 early gastric cancer), 161 patients were on single (94 aspirin, 56 thienopyridine, and 11 other agents), 51 on dual, and 3 on triple antiplatelets. Post-ESD bleeding rates were 12.8% in aspirin users, 3.6% in thienopyridine, 27.5% in dual, 33.3% in triple therapy, and 9.7% in the cessation and 15.0% in the continuation group. Multiple antiplatelets (odds ratio [OR], 2.41; 95% confidence interval [CI], 1.01 to 5.76) and specimen size ≥ 5.5 cm (OR, 2.84; 95% CI, 1.04 to 7.73) were the risk of bleeding, while continuation of thienopyridine (OR, 0.23; 95% CI, 0.05 to 1.09) and antiplatelets (OR, 1.83; 95% CI, 0.68 to 4.94) did not increase the risk of bleeding. CONCLUSIONS: Continuing thienopyridine and aspirin did not increase the risk of post-ESD. Multiple antiplatelet therapy and a large specimen size were independent risk factors of post-ESD bleeding.
Adenoma
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Aspirin*
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Hemorrhage
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Humans
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Risk Factors
8. Effects of different light on the ethology and melatonin secretion in depressive rats
Shu-Zhe ZHOU ; Wei-Min DANG ; Guo-Yi ZHANG ; Tian-Hang ZHOU ; Jian LIN ; Tian-Mei SI ; Ji-Tao LI ; Zhong-Kai HE ; Can-Tao ZHONG ; Sheng WANG ; Li ZHAO ; Yong-Zhi WANG ; Wei WEI ; Zhen-Lie HUANG ; Kuo ZHANG ; Zhi-Zhong CHEN ; Yi LIU ; Yang LIU ; Rong-Sheng ZHAO ; Hai-Ming SUN ; Si-Heng LI ; Rong-Feng NIU ; Yu-Zhen TONG ; Yan-Tao MA ; Xin YU
China Occupational Medicine 2016;43(01):8-14
OBJECTIVE: To observe the impact of energy saving light,incandescent light and circadian light on the ethology of depressive rats and explore its possible mechanism on affecting the secretion of melatonin. METHODS: Thirty rats aged 6weeks were randomly selected from 40 specific pathogen free health female SD rats after they adapted to the living environment,depressive rat models were established in the rats by bilateral ovariectomy combined with isolated living and chronic unpredictable mild stress stimulation at the age of 11-14 weeks. Then these 30 ovariectomized rats were randomly divided into 3 intervention groups,including an energy saving light group,an incandescent light group and a circadian light group,with 10 rats in each group. The rats in these 3 groups were given specific experimental light intervention for 3 weeks respectively at the age of 17 weeks. The other 10 rats were raised in conventional environment as the control group. Their body weights were measured at the age of 17,19,20 and 21 weeks. The ethology tests were carried out by sucrose preference test and the open-field test at the age of 7,14 and 20 weeks respectively. The melatonin levels in peripheral blood of 7 time points from 19: 30 to 8: 30 were measured in the rats at age of 21 weeks. One rat in each group at every time point was randomly selected for examination. RESULTS: At the age of 17 weeks before light-intervention,the body weights of rats in 4 groups showed no significant difference( P > 0. 05). After light-intervention,at the age of 17-20 weeks,the body weights of rats in 3 intervention groups were gradually increased with the increase of age( P < 0. 05).There was no significant difference between body weights of rats at the age of 21 weeks and those at the age of 20 weeks in each group( P > 0. 05). At age of 7 weeks,no significant differences were found in sucrose consumption and standing scores among these 4 groups( P > 0. 05). After the depressive models were established,at the age of 14 weeks before light-intervention,in rats of these 3 intervention groups,the sucrose consumption and standing scores were lower than those of the control group( P < 0. 05),and there was no significant difference found in the above 2 indexes among these 3intervention groups( P > 0. 05). At the age of 20 weeks after light-intervention,the sucrose consumption and standing scores were not significantly different from each other among the 4 groups( P > 0. 05). The peak levels of melatonin in the peripheral blood of rats in these 3 intervention groups were higher than that in the control group. The peak levels onsets of melatonin in peripheral blood of rats in the circadian light group and the energy saving light group were earlier or 2 hours delayed compared to that of control group,while it was similar between the incandescent light group and control group.CONCLUSION: The circadian light,the energy saving light and the incandescent light are similarly effective in improving the behaviors of depressive rats. The circadian light can delay the onset of peak level of melatonin in peripheral blood.
9.Application of three dimensional model in treatment of superolateral dislocation of mandibular condyle.
Xin XU ; Rong-xin DENG ; Si-min DENG ; Jun-lie YANG ; Jun CHEN
Journal of Zhejiang University. Medical sciences 2014;43(5):572-576
OBJECTIVETo assess the application of three-dimensional jaw model in treatment of superolateral dislocation of condyle.
METHODSNine patients with superolateral dislocation of condyle and symphyseal fractures were admitted in hospital from June 2008 to June 2013. Spiral CT scan on maxilla and mandible was performed,and three-dimensional jaw model was constructed with rapid prototyping technology. According to conditions of condylar superolateral dislocation model,the operation scheme was designed. The symphyseal fracture line was made and fracture was reduced on three-dimensional jaw model. Individualized prefabricated reconstructive titanium plate was made on symphyseal fracture model. Symphyseal fracture was replaced with individualized prefabricated mandibular reconstruction titanium plate according to occlusal relationship. At the same time,reduction of condylar superolateral dislocation was accomplished.
RESULTSOperations were successfully completed in 9 cases under guidance of three dimensional jaw model surgery. Operative incision was primarily healed,and occlusal relationship was restored. Postoperative CT scan showed that the locations of condyle in 9 cases were completely restored. Patients were followed-up for 6-28 months with a median of 18 months. The maximum of mouth opening was 3.1- 4.2 cm with a medians of 3.3 cm,and the occlusal relationship of all patients was normal after surgery.
CONCLUSIONThree-dimensional jaw model can show complete status of condylar superolateral dislocation and symphyseal fracture. The model can accurately shape symphyseal reconstructive titanium plate and restore condylar superolateral dislocation during reductive surgery.
Humans ; Joint Dislocations ; Mandibular Condyle ; physiopathology ; surgery ; Mandibular Fractures ; surgery ; Models, Anatomic ; Tomography, Spiral Computed ; Tomography, X-Ray Computed
10.Analysis of hepatitis C virus (HCV) subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong province.
Wei-lie CHEN ; Jing-min NIE ; Wei-ping CAI ; Xiao-zhen YUAN ; Feng-yu HU ; Shao-jing WEI ; Yang-bo TANG ; Fu-chun ZHANG ; Xiao-ping TANG
Chinese Journal of Hepatology 2011;19(10):729-933
OBJECTIVETo explore the transmission routes, genotypes/subtypes distribution and genetic character of HCV in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province.
METHODSReverse transcription (RT) nested PCR was performed to amplify the HCV NS5B gene region from 95 HIV/HCV co-infected and 99 HCV mono-infected individuals lived in Guangdong province. The PCR products were then sequenced for HCV subtyping. Genetic analysis was done by MEGA4 software.
RESULTS(1) HIV/HCV co-infected individuals infected HCV mostly through injection drug use (IDU, 78.9%), the HCV subtypes were identified as 6a (53.7%), 3a (17.9%), 1b (15.8%), 3b (11.6%) and 1a (1.0%) respectively, the genetic distance within subtype 1b was longer than those within other subtypes, the predominant HCV subtype in HIV/HCV co-infected individuals infected through IDU was 6a (60.0%). (2) HCV mono-infected individuals infected HCV mostly through blood or blood products transfusions (80.8%), the HCV subtypes were identified as 1b (67.7%), 6a (17.2%), 3a (6.1%), 2a (5.0%), 3b (2.0%), 4a (1.0%) and 5a (1.0%) respectively, the genetic distance within subtype 1b was also longer than those within other subtypes, the predominant HCV subtype in HCV mono-infected individuals infected through blood or blood products transfusions was 1b (76.2%).
CONCLUSIONThe diversity of HCV subtypes in HIV/HCV co-infected and HCV mono-infected individuals in Guangdong Province was high, both the major transmission route and HCV subtype between HIV/HCV co-infected individuals and HCV mono-infected individuals were different.
Adolescent ; Adult ; Aged ; Asian Continental Ancestry Group ; China ; epidemiology ; Coinfection ; virology ; Female ; Genotype ; HIV ; HIV Infections ; epidemiology ; virology ; Hepacivirus ; classification ; genetics ; Hepatitis C ; epidemiology ; virology ; Humans ; Male ; Middle Aged ; Phylogeny ; Young Adult

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