Objective:To discuss the scientificity and feasibility of risk-based monitoring strategies in Investigator initiated Trials.Methods:" Guideline for Good Clinical Practice" promulgated by NMPA, " Oversight of Clinical Investigations-a Risk-based Approach to Monitoring" and " A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers Guidance for Industry DRAFT GUIDANCE" promulgated by the US FDA and other documents were analyzed, the practical experience of Investigator initiated Trials was also summarized.Results:It was recommended that clinical investigators use risk-based monitoring strategies in Investigator initiated Trials. The main idea of risk-based monitoring is to determine the key process and key data of the study, carry out risk rating on the project, and adopt corresponding monitoring methods according to the risk level when formulating the monitoring plan. At the same time, during the clinical trial development process, the risk and data quality of the research center should be regularly evaluated to grasp the risk changes of different centers. In accordance with trends, adjust the method, content and frequency of monitoring.Conclusions:To apply risk-based monitoring strategies in Investigator initiated Trials is scientificity and feasibility. Risk based monitoring can meet the data quality requirements of clinical trials, without affecting the analysis results of the main outcomes, and can further improve the efficiency and effectiveness of monitoring.

目的 分析心血宁胶囊改善伴有高Hcy水平(>15?μmol/L)的缺血性卒中患者短期功能预后的效果.方法 选取心血宁胶囊用于缺血性卒中伴高Hcy水平患者的有效性和安全性研究(研究周期2018年10月30日-2019年12月27日)中完成3个月药物治疗及随访的患者作为研究对象.根据研究用药的不同,将患者随机分成心血宁组(给予心血宁胶囊0.4克/粒、2粒/次、3次/日,叶酸片模拟剂2片/次、1次/日)、叶酸组(给予心血宁胶囊模拟剂2粒/次、3次/日,叶酸片0.4毫克/片、2片/次、1次/日)和安慰剂组(给予心血宁胶囊模拟剂2粒/次、3次/日,叶酸片模拟剂2片/次、1次/日),连续用药3个月.采用χ2趋势检验比较患者治疗3个月时mRS评分的变化情况.结果 本研究纳入238例患者,平均年龄为64.49±12.48岁.其中,心血宁组患者79例,叶酸组患者86例,安慰剂组患者73例.治疗3个月时,心血宁组mRS 0～1分的比例为91.14％(72/79),叶酸组为80.23％(69/86),安慰剂组为80.82％(59/73).趋势检验结果显示,叶酸组与安慰剂组相比mRS评分没有趋势关系(P=0.89),心血宁组与安慰剂组相比mRS评分有下降趋势(P=0.04),心血宁组与叶酸组相比mRS评分有下降趋势(P=0.03).结论 对于伴有高Hcy水平的缺血性卒中患者,使用心血宁胶囊治疗可能改善患者3个月功能预后.

Objective:To explore the key points and implementation of establishing a whole-process clinical research management system.Methods:Based on the problems in practice, combined with project management experiences, this article analyzed the construction of the whole-process clinical research management system.Results:The establishment of the management system provides a comprehensive and sustainable safeguard for clinical research, as well as the improvement of efficiency and quality of clinical research.Conclusions:The establishment of an effective whole-process management system for clinical research project is a useful exploration of the research service model in China.

Background and purpose The clinical significance of carbon dioxide combining power (CO2CP) in ischaemic cerebrovascular disease is not well established, and the role of CO2CP in the prognosis of acute ischaemic stroke (AIS) or transient ischaemic attack (TIA) has not been reported. The objective of the study was to investigate the associations between CO2CP and clinical outcomes in patients with AIS or TIA.Methods Data were derived from the China National Stroke Registry III. Patients were classified into five groups by quintiles of CO2CP levels and three groups according to the normal range of CO2CP (23–29 mmol/L). Multivariable Cox and logistic regressions were adopted to explore the associations of CO2CP levels with all-cause death and poor functional outcomes (modified Rankin Scale (mRS) 3–6/2–6) at 3 months and 1 year.Results Among 9531 patients included in the study, the median (IQR) CO2CP was 24.9 (23.0–27.0) mmol/L. After adjustment for potential confounders, patients in the first CO2CP quintile (21.1–23.3 mmol/L) had higher risk of all-cause death and poor functional outcomes (mRS score of 3–6/2–6) (HR or OR with 95% CI 2.37 (1.32 to 4.25), 1.49 (1.20 to 1.83) and 1.21 (1.03 to 1.42), respectively) compared with those in the fourth quintile. Similar results were found for outcomes at 1 year. Furthermore, all associations were also significant when CO2CP was <23 mmol/L compared with CO2CP of 23–29 mmol/L.Conclusions Decreased CO2CP was associated with high risk of all-cause death and poor functional outcomes in patients with AIS or TIA.

Backgrounds Embolic stroke is one of the main mechanisms of ischaemic stroke. Even if treated with recommended antithrombotic agents, stroke recurrence remains high. The Shuxuetong injection, a purified extract of traditional Chinese medicine widely used for thrombus diseases in clinical practice in China, could be a promising agent to prevent stroke recurrence. Aims To describe the design of the Shuxuetong injection for prevention of recurrence in acute ischaemic stroke with embolism mechanisms. Design The Shuxuetong for Prevention of recurrence in Acute Cerebrovascular events with Embolism (SPACE) trial is a multicentre, randomised, double-blind, placebo-controlled, parallel-group, superiority trial to evaluate the efficacy and safety of Shuxuetong injection in reducing recurrence or silent new ischaemic lesions on patients with acute embolic stroke within 10 days. An estimated 2416 patients with embolic stroke within 72 hours of symptom onset from 80 hospitals will be randomly assigned to one of two groups receiving Shuxuetong injection or placebo injection for 10 days. The primary endpoint is symptomatic or asymptomatic new cerebral infarction within 10 days after randomisation. Conclusion The SPACE Trial will provide valuable evidence for the efficacy and safety of Shuxuetong injection for the prevention of stroke recurrence in patients with imaging-defined embolic stroke. Clinical trial registration NCT03090113 .

Stroke becomes the second leading cause of death in the world, and has also been the leading cause of death in China in recent years, which gives rise to a heavy burden on families and society. The risk factors related to death of stroke in recent years are expounded, and the scale of adverse prognosis prediction of stroke and the scale verified in Chinese population are summarized in this paper, so as to provide an important reference basis for the prediction of stroke prevention, management and death outcome in China.

Objective To investigate the status of secondary prevention medications adherence in patients with ischemic cerebrovascular diseases in China, and the relationship between 3-month medication adherence and 1-year recurrent stroke after discharge in patients with acute ischemic stroke or TIA. Methods Patients diagnosed with first-ever acute ischemic stroke or TIA from Stroke and Transient Ischemic Stroke Treatment Adherence Registry in China were enrolled in this study. Medication adherence was defined as taking all secondary prevention medications prescribed at discharge continuously and regularly during the 3-month follow up. Multivariate logistic regression analysis was used to analyze the relationship between 3-month medications persistence and 1-year recurrent stroke after discharge. Results A total of 2768 patients were selected, with the mean age 62.3±11.4 years and 988 (35.7%) female patients. 2016 patients (72.8%) persisted in taking all secondary prevention medications during the 3-month follow up; the drug adherence rate were 95.3%, 90.9%, 90.2%, 85.4% and 73% for antiplatelet agents, blood glucose-lowering drugs, antihypertensive drugs, lipid-lowering drugs, and anticoagulation agents, respectively. The diabetes history (OR 1.40, 95% CI 1.14-1.73, P=0.0016) and the cessation history of blood glucose-lowering drugs might be the influence factors for drugs adherence, while there were no statistical significance after adjusting for the confounding factors. After adjusting for the confounders including age, sex, medical history and so on, logistic regression analysis showed 3-month persistence of secondary prevention medications was an independent influence factor for recurrent stroke at 1 year after discharge ( OR 0.36, 95% CI 0.14-0.91, P=0.0301). Conclusions The 3-month persistence of secondary prevention drugs was much more satisfactory compared to the previous results reported in Chinese patients. The 3-month persistence of secondary prevention medications was an independent influence factor for recurrent stroke at 1 year after discharge.

目的 调查急性缺血性卒中伴吞咽困难的住院患者,并探索吞咽康复治疗的影响因素及其与预后的相关性.方法 选取2012-2013年的1 581例多中心的缺血性卒中住院患者,吞咽困难的临床诊断由康复治疗师进行专业的床边吞咽评估得出.吞咽困难的康复治疗包括吞咽康复训练、电刺激或磁刺激,以及辅助治疗等.随访时间为12个月,终点事件包括全因死亡、卒中复发和功能预后不良.采用多因素Logistics回归模型对吞咽困难患者进行康复治疗的影响因素进行分析,采用Cox回归模型对吞咽困难患者进行康复治疗与预后的相关性进行分析.结果 本研究共纳入1581例伴吞咽困难的急性缺血性卒中患者,其中962例(60.8％)进行了吞咽康复治疗.进行吞咽康复治疗的影响因素包括:入院时较低的国立卫生研究院卒中量表评分、接受肢体康复治疗、深静脉血栓预防、颈动脉血管成像检查以及在年出院数较高的医院住院(均P＜0.05).与未进行吞咽康复治疗的患者相比,行吞咽康复治疗的患者12个月全因死亡风险较低[危险比(hazard ratio,HR):0.76;95％置信区间(confidence interval,CI):0.60～ 0.95],卒中复发比例较低[HR:0.73;95％CI:0.55～0.96],功能预后不良的比例较低(比值比:0.68;95％ CI:0.50～0.93)(均P＜0.05).结论 伴吞咽困难的急性缺血性卒中患者进行吞咽康复治疗的影响因素包括:入院时NIHSS评分,医院的年卒中出院人数,是否行肢体康复、深静脉血栓预防和颈动脉血管成像检查等.吞咽康复治疗可改善伴吞咽困难的急性缺血性卒中患者12个月的预后.

Objective To explore the data matching profile between stroke cohort in large multicenter study and the administrative data, and to provide new ideas and methods for data quality control in similar clinical studies. Methods The data of 12 112 inpatients with ischemic stroke who completed the 90-day follow-up from multicenter clinical trial from 2015 to 2017 were selected. The selected data were matched with all the deaths in the China National Disease Surveillance Points System from 2015 to 2017. The differences in regional and hospital distribution and patients characteristics were compared and analyzed between the group of unmatched patients with no death information in stroke cohort study while who had died as shown in China National Disease Surveillance Points System and the group of matched patients with the same death information in the two data. Results There were no statistically significant differences in regional and hospital distribution and patients characteristics between the two groups. However, according to the data trend, the unmatched rate of death information in the patients with NIHSS ≤3 on admission was higher than that in the patients with NIHSS >3 on admission (11.36% vs 6.56%), and the unmatched rate of death information in the patients living alone was higher than that in the patients living with family (13.16% vs 7.65%). Conclusions It is more difficult to obtain accurate death outcome information in patients with relatively mild neurologic impairment and patients living alone after discharge. The database matching method can make up for the lack of follow-up information in large multicenter cohort studies, which can provide accurate death outcome information of patients for stroke cohort studies.

Objective We investigated the effect of statin use during hospitalization in reducing short-term stroke recurrence of patients with acute ischemic stroke and chronic kidney diseases (CKD). Methods Data of first-ever ischemic stroke patients without a history of pre-stroke statin use was derived from the China National Stroke Registry (CNSR). Patients were stratified according to estimated glomerular filtration rate (eGFR): normal renal function [eGFR≥90 ml/(min·1.73 m2)], mild CKD [60 ml/(min·1.73 m2)≤eGFR<90 ml/(min·1.73 m2)] and moderate CKD [eGFR<60 ml/(min·1.73 m2)]. Multi-factors logistic regression analysis was used to evaluate the association between statin use during hospitalization and stroke recurrence with different renal functions at 3-month follow-up. Results Among 5951 patients included, 2595 (43.6%) patients were on statin use during hospitalization after stroke. Compared with non-statin group, statin use during hospitalization was associated with decreased stroke recurrence in patients with mild CKD [odds ratios (OR) 0.69, 95% confidence interval (CI) 0.50-0.95,P=0.02] and moderate CKD (OR 0.48, 95%CI 0.28-0.83,P=0.009) at 3-month follow-up, respectively. Whereas in patients with normal renal function, no significant benefit from statin therapy was detected (OR 0.80, 95%CI 0.60-1.06,P=0.12). Conclusion Statin use during hospitalization was associated with decreased stroke recurrence in ischemic stroke patients with mild and moderate CKD at 3-month follow-up, but not in patients with normal renal function in Chinese population. Further studies are needed to confirm this finding.

Objective To investigate the correlation between functional prognosis and plasma oxidized low-density lipoprotein (oxLDL) in acute ischemic stroke (AIS) patients with different levels of renal function. Methods All subjects were recruited from the Study of Oxidative Stress in Patients With Acute Ischemic Stroke (SOS-Stroke). Plasma level of ox-LDL was measured by enzyme-linked immuno sorbent assay (ELISA). Patients were stratified by the calculated glomerular filtration rate, and followed up at 1 year after stroke onset to assess the modified Rankin Scale (mRS) score. Analysis of the relationship between oxLDL and poor prognosis (modified Rankin scale ≥3 points) in patients with different levels of renal function were performed. Results A total of 3284 patients were enrolled in this study, of whom 877 (26.71%) had poor functional outcomes. After grouping according to renal function, there were 1241 cases of normal control, 924 cases of mild abnormality, and 242 cases of moderate-severe abnormality. Patients of poor prognosis in all groups were respectively 344 (21.70%) cases of normal group, 371 (28.65%) cases of mild abnormal group, and 162 cases (40.10%) of moderate-severe abnormal group. The plasma level of oxLDL had a significant effect on 1-year mRS score in the patients with normal and mild damage renal function: in normal renal function group, the mRS score increased by 0.12 points for each standard deviation increase in oxLDL [OR 0.12, 95%CI 0.05-0.19, P=0.0009], and the risk of poor prognosis increased by 20% (OR 1.20, 95%CI 1.02-1.40, P=0.0271); in mild renal impairment group, the mRS score increased by 0.16 points for each standard deviation increase in oxLDL. (OR 0.16, 95%CI 0.07-0.25,P=0.0007), and the risk of poor prognosis increased by 21% (OR 1.21, 95%CI 1.03-1.41, P=0.0190); however, in moderate-severe renal impairment group, plasma oxLDL levels did not significantly affect the mRS score. Conclusion The increased of plasma oxLDL levels in AIS patients with normal renal function and mild renal impairment are associated with the poor prognosis within 1 year.