国内癌因性疲劳中医药相关临床试验注册现状分析

目的 通过分析中国临床试验注册中心(Chinese clinical trial registry，ChiCTR)注册的与中医药干预癌因性疲劳(cancer-related fatigue，CRF)相关的临床试验，探讨其试验注册现状。方法 检索ChiCTR数据库收录的从建库至2022年6月2日与中医药相关的CRF临床研究注册试验，对检索结果进行筛选并提取所需数据信息，运用WPS Office软件的表格功能对纳入研究数据进行统计分析，并归纳临床试验特征。结果 最终纳入36项CRF中医药相关临床试验，覆盖全国6个省、3个直辖市，其中包括干预性研究34项，观察性研究2项，招募样本量5 327例，干预措施包括内服药物疗法、中药注射液、外治法和中医传统功法。结论 目前有关CRF中医药临床试验注册数量总体呈上升趋势，试验以随机对照试验(randomized controlled trial, RCT)研究居多，干预性研究为主，其空间分布欠均衡，且注册信息的严谨性与结局指标的规范性待进一步提高。     

肝功能障碍患者异丙酚药代动力参数的Meta分析

目的系统评价肝功能障碍患者异丙酚药代动力学参数，为临床异丙酚个体化用药提供循证医学证据。方法计算机检索MEDLINE（1975年至2010年10月）、OVID、Springerlink、中国期刊全文数据库CNKI（1979年至2010年10月）、重庆维普中文科技期刊全文数据库（1989年至2010年10月）、万方数据资源系统（1996年至2010年10月）、中国生物医学文献数据库（1978年至2010年10月）等，并辅以手工检索。收集所有关于肝功能障碍患者异丙酚药代动力学随机对照试验和非随机对照试验公开发表的文献，使用Cochrane系统评价方法，评价纳入研究的方法学质量并提取有效数据，用RevMan4．2软件进行Meta分析。结果共检索到153篇英文文献和6篇中文文献．最后纳入6篇非随机对照试验。Meta分析结果显示：①肝功能障碍患者与肝功能正常患者相比，异丙酚中央室分布容积和清除率均未见差异有统计学意义。②两者在异丙酚半衰期和速率常数上也未见差异有统计学意义（P〉0．05）。③肝功能障碍患者异丙酚稳态分布容积大于对照组，差异有统计学意义[加权均数差1．24，95％可信区间（0．38，2．10），P=0．005]。结论肝功能障碍患者除异丙酚稳态分布容积明显高于肝功能正常患者外，其他指标差异无统计学意义，提示肝功能障碍患者异丙酚麻醉时不需降低用量，上述结论尚需进一步验证。     

Effects of Exercise on Cancer-related Fatigue and Quality of Life in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Meta-analysis of Randomized Clinical Trials

Objective To gain insight on how exercise affects the outcomes of prostate cancer patients treated with androgen deprivation therapy, specifically cancer-related fatigue (CRF) and quality of life (QoL). Methods Systematic searches for randomized clinical trials (RCTs) evaluating the effects of exercise on CRF and QoL of prostate cancer patients receiving androgen deprivation therapy were carried out to identify the eligible studies from EMBASE, PubMed and Cochrane library. Related data were extracted from eligible studies and then subjected to Reviewer Manage 5.3 for analysis. Standardized mean differences (SMD) and its 95% confidence interval (CI) were calculated. Results In all, 10 RCTs involving 841 prostate cancer patients (448 of whom exercised and 393 did not) were included in this study. With respect to CRF, there was good consistency among different studies, and it was remarkably reduced in the exercise group (SMD=?0.32, 95%CI:?0.45 to?0.18, P<0.00001,n=784). In regards to QoL, there was also good consistency among different studies, and it was also improved significantly in the exercise group (SMD=0.21, 95%CI: 0.08 to 0.34,P=0.002, n=841). Conclusion Exercise both reduced CRF and improved QoL in prostate cancer patients receiving androgen deprivation therapy.     

A Data Capture System for Outcomes Studies that Integrates with Electronic Health Records: Development and Potential Uses

In conventional clinical studies, the costs of data management for quality control tend to be high and collecting paper-based case report forms (CRFs) tends to be burdensome, because paper-based CRFs must be developed and filled out for each clinical study protocol. Use of electronic health records for this purpose could result in reductions in cost and improvements in data quality in clinical studies. The purpose of this study was to develop a data capture system for observational cancer clinical studies (i.e. outcomes studies) that would integrate with an electronic health records system, to enable evaluation of patient prognosis, prognostic factors, outcomes and drug safety. At the Outpatient Oncology Unit of Kyoto University Hospital, we developed a data capture system that includes a cancer clinical database system and a data warehouse for outcomes studies. We expect that our new system will reduce the costs of data management and analysis and improve the quality of data in clinical studies. Keiichi Yamamoto and Shigemi Matsumoto contributed equally to this work.     

支架置入术与内膜切除术治疗颈动脉狭窄的系统评价

目的:评价颈动脉血管成形术和颈动脉内膜切除术治疗颈动脉狭窄的近期临床疗效和安全性。方法:电子检索中国学术期刊网全文数据库(1996～2006年)、Medline(1996～2006年)和Cochrane图书馆(2006年12月前已发表的文献和已注册但未发表的临床试验),并与研究者取得联系获得更多的相关研究资料。纳入比较颈动脉血管成形术和内膜切除术治疗颈动脉狭窄的随机对照试验,比较两种治疗方法术后30d内卒中发生率和卒中与死亡的联合发生率。以卒中发生率作为疗效评价指标,以卒中和死亡的联合发生率作为安全性评价指标。2名评价员独立检索和提取资料,对纳入试验的方法学质量进行评价。结果:在术后30d内的卒中发生率方面,共纳入4项临床试验的2541例患者,其中颈动脉血管成形术组1278例,颈动脉内膜切除术组1263例,在术后30d的卒中和死亡的联合发生率方面,纳入5项临床试验,共2760例患者,其中颈动脉血管成形术组1385例,颈动脉内膜切除术组1375例。分析结果显示,在术后30d内的卒中发生率方面,颈动脉血管成形术与颈动脉内膜切除间差异无统计学意义(OR:1144;95%CI:1105～1197,Z=2128,P=0...     

血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂预防房颤发生的Meta分析

目的:评价血管紧张素转换酶抑制剂(ACEI)/血管紧张素Ⅱ受体拮抗剂(ARB)预防房颤发生/复发的效果。方法:计算机检索PubMed、ScienceDirect、Embase、Ovid、Cochrane图书馆临床对照试验资料数据库、中国生物医学文献数据库(2001年1月-2011年4月)中比较ACEI或ARB类药与其它药治疗心血管疾病的随机对照临床研究,按照入选与排除标准筛查文献,提取相关资料,采用Review Manager 4.2.9对所提取数据进行Meta分析。结果:共纳入14项随机对照研究,均为英文,研究病例数总计40 217例,其中治疗组20 260例,对照组19 957例。Meta分析表明,ACEI或ARB与其它药相比可预防房颤发生,其差异有统计学意义[OR=0.69,95%CI(0.63~0.75),P<0.000 1]。对不同基础疾病的亚组分析显示,高血压患者中服用ACEI/ARB较其他降压药在预防房颤发生方面差异有统计学意义[OR=0.69,95%CI(0.61~0.78),P<0.000 1];慢性心衰患者服用ACEI/ARB较其他常规治疗药可预防房颤发生[OR=0.61,95%CI(0.53~0.71),P<0.000 1];房颤患者中服用ACEI/ARB较其抗心律失常药可显著降低房颤复发率[OR=0.82,95%CI(0.69~0.98),P=0.03]。结论:在高血压、慢性心衰及房颤患者,服用ACEI/ARB类药可降低房颤发生/复发率。     

Scientific Section: Coronary Artery Surgery, Task Force Appointed by the Conference of Deputy Ministers of Health: 2. Results, indications and recommendations

The large majority of reported studies of patients treated by aortocoronary bypass have not been randomized clinical trials, and hence must be interpreted with great caution.

Review of the seven randomized clinical trials in the literature leads to only one firm, positive conclusion: aortocoronary bypass results in a reduction in the morbidity of coronary artery disease, due to the alleviation of cardiac pain, for at least 3 years. In addition, there is some evidence that mortality for symptomatic patients with significant left main-stem coronary artery stenosis may be reduced by coronary artery bypass surgery. A significant effect on mortaliy form other forms of coronary artery disease has not yet been conclusively demonstrated but also has not been excluded. Most of the reports are preliminary and involve small numbers of patients followed for relatively short periods. The operation is still being improved. It is to be hoped that the randomized trials, involving large numbers of patients, now in progress will supply some of these answers.

Aortocoronary bypass surgery is the treatment of choice for patients with stable cardiac pain that is disabling despite adequate treatment, or when adequate treatment is impractial; for patients with unstable cardiac pain, uncontrolled despite adequate treatment; and for symptomatic patients with critical stenosis of the left main-stem coronary artery.

     

慢性肾衰竭合并上消化道黏膜病变的临床治疗

目的探讨慢性肾衰竭（CRF）并发上消化道黏膜病变的有效治疗方法。方法对42例CRF并发上消化道疾病患者和40例非CRF的上消化道疾病患者进行胃镜检查了解黏膜病变;随机对照研究麦滋林-S颗粒辅助治疗的临床疗效。结果CRF患者的上消化道症状与黏膜病变均较重,麦滋林-S结合泮托拉唑治疗20d后临床症状改善,胃镜下表现及病理组织学等方面均有不同程度的好转,发现麦滋林-S治疗组的治疗效果较对照组在CRF患者中有显著疗效（P〈0．05）。结论CRF患者上消化黏膜病变较重,麦滋林-S结合泮托拉唑治疗具有显著疗效。     

新辅助化疗加手术治疗局部晚期宫颈癌的Meta分析

目的 评价新辅助化疗治疗局部晚期宫颈癌的临床疗效.方法 电子检索Cochrane图书馆、MEDLINE、EMBASE、PubMed、CBMdisc数据库,收集符合纳入标准的文献,提取资料、评价纳入研究的方法学质量,并提取有效数据进行Meta分析.结果 符合纳入标准共5篇文章,4篇为前瞻性随机对照试验,1篇为回顾性病例对照研究.新辅助化疗对局部晚期宫颈癌的5年生存率没有影响(相对危险度1.07,95％可信区间0.88～1.29,P=0.51),但提高了局部晚期宫颈癌的5年无瘤生存率(相对危险度1.13,95％可信区间1.0～1.27,P=0.01);降低了术后淋巴结转移率及宫旁浸润率(相对危险度0.48,95％可信区间0.34～0.7,P＜0.000 1;相对危险度0.54,95％可信区间0.36～0.83,P＜0.001).结论 新辅助化疗可用于治疗局部晚期宫颈癌,可降低术后宫旁浸润率及淋巴结转移率.但纳入的研究少且都为小样本的研究,因此新辅助化疗对局部晚期宫颈癌的疗效有待进一步大样本、高质量、多中心、随机双盲对照试验加以证实.     

Swedish guidelines for registry-based randomized clinical trials

Abstract

During the last decade Sweden has invested in a national infrastructure for collection of structured clinical data in the form of healthcare registries (in Sweden known as Kvalitetsregister). These data can be combined with other public data using the national personal identifiers that are issued to Swedish citizens. The healthcare registries have an almost complete coverage of Swedish healthcare, and a large network of clinicians is involved in the quality assurance and continuous improvement of healthcare using these registries. Uppsala Clinical Research Center (UCR) has been a technology provider of large-scale national registries and has a strong background in clinical trial management. This effort combines the areas of healthcare registries and clinical trials into a novel way of performing clinical trials to be able to: 1) run clinical trials as an integrated part of normal clinic workflow; and 2) leverage the nationwide network of outcome reporting. This strategy was shown to be successful in the TASTE (Thrombus Aspiration in Myocardial Infarction) study. When TASTE had been published, the New England Journal of Medicine wrote a perspective on the study calling it ‘The randomized registry trial—the next disruptive technology in clinical research?’ Since then several studies have been conducted in this way with great success. UCR has been appointed, by Clinical Studies Sweden and the Swedish Research Council, to develop the Swedish national guidelines for registry-based randomized clinical trials in order to ensure the possibility for more organizations to run this kind of study. This paper describes key concepts of register-based randomized clinical trials and the development of Swedish national guidelines.     

中医药临床研究者使用电子化数据管理系统的依从性问题及对策

在信息化飞速发展的今天,实施电子化临床试验数据管理是中医药临床试验数据管理的发展趋势,然而在项目实施过程中发现研究者对电子化数据管理的依从性不佳,并发现较差的依从性会对控制临床试验数据的质量产生直接的影响。在中医药大规模临床试验中采用电子化数据管理模式后,部分研究中心及研究者根据临床试验研究中依从性的现状,分析原因、提出对策。     

基于句子级Lattice-长短记忆神经网络的中文电子病历命名实体识别

目的 提出一种基于Re-entity新分词方法的条件随机场（CRF）模型,并与双向长短记忆神经网络（BiLSTM）-CRF和Lattice-长短记忆神经网络（LSTM）进行比较。方法 比较了现有实体识别方法和模型后,针对2018年全国知识图谱与语义计算大会（CCKS2018）任务一“电子病历命名实体识别”,提出基于Re-entity的CRF、BiLSTM-CRF、Lattice-LSTM方法,并在不同语料库训练不同参数级别的字符向量集。分别将各方法引入神经网络模型中进行模型性能对比实验,最后分别基于句子级和篇级输入句长进行对比研究。结果 CRF模型在最优特征工程的结果下引入Re-entity方法后性能得到提高,句子级的Lattice-LSTM模型在该任务上取得了89.75%的严格F1-measure,优于CCKS2018任务一的最高结果（89.25%）。结论 基于Re-entity新分词方法的CRF模型可利用中文临床药物知识库有效提高电子病历中药物的识别率,Re-entity方法可改善数据预处理阶段分词导致的错误累加,Lattice结构可以更好地结合字符和词序列的潜在语义信息,同时句子级输入能有效提高神经网络模型的识别准确率。     

拉米夫定治疗乙型肝炎病毒相关性肝衰竭疗效的Meta分析

目的系统评价拉米夫定治疗乙型肝炎病毒（HBV）相关性肝衰竭的疗效。方法检索1989年1月至2007年7月有关在常规内科治疗的基础上加用拉米夫定后对患者病死率、总胆红素（TBIL）及凝血酶原活动度（PTA）影响的文献,应用Meta分析的方法以比值比（OR）或加权平均数（WMD）为效应量进行合并分析。结果上述研究指标纳人研究文献分别为13、10篇和10篇,合并效应量及95％可信限（95％CI）分别为0．29（95％CI：0．21,0．40）、-0．88（95％CI：-1．27,-0．48）和0．60（95％CI：0．42,0．78）。结论与常规内科治疗组比较,加用拉米夫定可以显著降低肝衰竭患者的病死率,改善患者的TBIL和PTA水平。     

6月和9个月间歇疗法对HIV和并活动性肺结核治疗的疗效评价:Meta分析

目的:评价6月和9个月间歇疗法对HIV感染病人活动性肺结核治疗疗效的影响。方法:计算机检索1992年～2012年12月Cochrane图书馆、PubMed、Embase、中国知网和万方数据库等,收集不同抗结核疗程方案治疗HIV并活动性结核感染的随机对照试验(RCT)进行了系统评价。2名研究者独立进行资料提取和文献质量评估,采用RevMan4.2软件进行Meta分析。结果:纳入2个随机对照试验,共包括484例受试对象。结果表明,6个月抗结核治疗方案与6个月以上的方案治疗HIV感染病人活动性肺结核的失败率没有统计学差异1.39(0.25,7.68)。结论:6个月以上抗结核治疗方案在失败率方面没有比6个月治疗方案更低。上述结论尚需进一步通过开展大规模、高质量的基础和临床研究来证实。     

丁苯酞治疗血管性痴呆疗效及安全性的系统评价

目的系统评价丁苯酞治疗血管性痴呆的疗效和安全性。方法通过计算机检索及手工检索,全面收集丁苯酞治疗血管性痴呆的随机对照试验(RCT),按Cochrane协作网系统评价的方法进行评价。结果共纳入8个研究(717例患者)。8个研究采用MMSE评价患者痴呆程度改善情况,Meta分析示:丁苯酞组优于对照组[MD=3.76,95%CI(2.95,4.57)];5个研究(405例)采用ADL评价患者日常生活能力改善情况,Meta分析示:丁苯酞组优于对照组[MD=4.99,95%CI(2.29,7.69)];4个研究进一步采用CDS和HDS(各2个研究,计376例)评价患者痴呆程度改善情况,Meta分析示:丁苯酞组优于对照组[SMD=1.17,95%CI(0.36,1.97)]。3个研究(265例)给予临床有效性评价,Me-ta分析示:丁苯酞组优于对照组[RR=1.27,95%CI(1.09,1.47)]。共6个研究报道了药品不良事件,均无严重不良事件发生。结论本系统评价结果提示丁苯酞治疗血管性痴呆有效而且安全,但尚需更多更高质量的随机双盲对照试验进一步证实。     

Analysis and reporting of factorial trials: a systematic review

CONTEXT: Although factorial trials have become common, standards for the analysis and reporting of such trials have not been established and, despite concerns about the possibility of unrecognized interactions between therapies in factorial trials, the magnitude of this potential problem is unknown. OBJECTIVE: To examine the rationale, methods, and analysis of randomized factorial trials. DATA SOURCES AND STUDY SELECTION: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register using the terms factorial, interaction, 2 x 2, 2 by 2, and incremental to identify factorial randomized trials published from January 2000 to July 2002. To identify trials missed by the electronic search, we performed a hand search of English-language trials in a defined topic area (using the term myocardial ischemia [exp]) listed in MEDLINE (1966-2002), EMBASE (1980-2002), and the Cochrane Controlled Trials Register, as well as all trials in any topic area published in December 2000, excluding trials reporting only continuous surrogate end points. The final set of 33 eligible publications described 29 unique trials. DATA EXTRACTION: Two investigators independently identified factorial trials, generated a list of items affecting validity of results, and abstracted these items from each trial. DATA SYNTHESIS: The sensitivity of electronic searching for identifying factorial trials was 76%. Our 3-pronged search strategy identified 44 factorial trials with clinically important binary outcomes: 36 (82%) were done for reasons of efficiency (testing 2 interventions in the same patient population), and 8 (18%) were done to assess the incremental benefits of combining the 2 treatments. All but 1 of the trials reported treatment effects by comparing all patients who received treatment A (ie, those receiving either A alone or both A and B) vs all those not receiving treatment A (ie, those receiving either B alone or neither A nor B). Twenty-nine of the 44 trials (66%) reported the data from each of the treatment groups separately; 26 trials (59%) reported testing for interactions between the treatments. Only 2 of 31 (6%) comparisons demonstrated a statistically significant interaction between the 2 treatments. CONCLUSIONS: Accurate interpretation of factorial trials depends on the transparent reporting of data for each treatment cell. Despite concerns about unrecognized interactions, our findings suggest that investigators are appropriately restricting their use of the factorial design to those situations in which 2 (or more) treatments do not have the potential for substantive interaction.     

Integrated traditional and Western medicine for treatment of depression based on syndrome differentiation:a meta-analysis of randomized controlled trials based on the Hamilton depression scale

OBJECTIVE:To systematically review the benefits of integrated traditional and Western medicine therapies based on the Hamilton depression scale(HAMD) following syndrome differentiation of depression.METHODS:We searched six English and Chinese electronic databases for randomized clinical trials(RCTs) on integrated traditional and Western medicine for treatment of depression.Two authors extracted data and independently assessed the trial quality.RevMan 5 software was used for data analyses with an effect estimate presented as weighted mean difference(WMD) with a 95% confidence interval(CI).RESULTS:Seven RCTs with 576 participants were identified for this review.All trials were eligible for the meta-analysis and were evaluated as unclear or having a risk of bias.Meta-analysis showed,compared with Western medicine alone,integrated traditional and Western medicine based on syndrome differentiation could improve the effect of treatment represented by the HAMD [WMD=-2.39,CI(-2.96,-1.83),Z=8.29,P<0.00001].There were no reported serious adverse effects that were related to integrated traditional and Western medicine based therapies in these trials.CONCLUSIONS:Integrated traditional and Western medicine based therapies for the syndrome differentiation of depression significantly improved the HAMD,illustrating that combining therapies from integrated traditional and Western medicine for treatment of depression is better than Western medicine alone.However,further large,rigorously designed trials are warranted due to the insufficient methodological rigor seen in the trials included in this study.     

经动脉栓塞治疗腹主动脉瘤患者腔内修复术后持续性Ⅱ型内漏的荟萃分析

目的 评价经动脉栓塞治疗腹主动脉瘤腔内修复术(EVAR)术后持续性Ⅱ型内漏的临床效果.方法 通过计算机检索和人工检索所有相关文献,确定所有关于经动脉栓塞治疗EVAR术后Ⅱ型内漏的文献.由两位作者独立完成所有相关文献的回顾和提取.研究终点为技术成功率、临床成功率、术中死亡率及术后严重并发症.结果 共有56篇相关文献,没有RCT研究.7篇文献(含129例Ⅱ型内漏患者)符合纳入标准.技术成功率均数为78.3%(95%CI:78.3%±7.3%).在3项研究中瘤腔直径稳定不变和缩小的发生率分别为72.2%和27.8%、40.0%和60.0%、31.3%和68.7%,故瘤腔直径没有增大的临床成功率均为100.0%;而在另3项研究中,其Ⅱ型内漏的消失率分别为61.5%、20.0%、78.9%.没有术中死亡及术后严重并发症的发生.结论 根据现有证据,经动脉栓塞致内漏的侧支或(和)瘤囊是治疗EVAR术后Ⅱ型内漏的主要方法,具有高技术成功率、高临床成功率且没有严重并发症和术中死亡的发生.但鉴于目前此类临床研究病例较少,还有待于更多的高质量的随机研究来证实.     

Data standards for clinical research data collection forms: current status and challenges

Case report forms (CRFs) are used for structured-data collection in clinical research studies. Existing CRF-related standards encompass structural features of forms and data items, content standards, and specifications for using terminologies. This paper reviews existing standards and discusses their current limitations. Because clinical research is highly protocol-specific, forms-development processes are more easily standardized than is CRF content. Tools that support retrieval and reuse of existing items will enable standards adoption in clinical research applications. Such tools will depend upon formal relationships between items and terminological standards. Future standards adoption will depend upon standardized approaches for bridging generic structural standards and domain-specific content standards. Clinical research informatics can help define tools requirements in terms of workflow support for research activities, reconcile the perspectives of varied clinical research stakeholders, and coordinate standards efforts toward interoperability across healthcare and research data collection.     

临床试验计量重复测量资料的统计

目的 探讨药物临床试验计量重复测量资料统计分析方法的选择。方法 通过实例列出各种分析方法并进行比较。结果 临床药物研究资料常为重复测量资料，比较治疗组与对照组测量值是否有显著性差别，在统计方法选择策略上一种是对一个代表性值进行比较，采用传统的统计方法如两独立样本t检验、方差分析和协方差分析；另一种策略是采用混合效应模型对整个研究过程中所有时点的测量值进行分析。结论 两种统计策略均可以采用，但混合效应模型是较好的分析方法。药物临床试验研究资料常是重复测量资料，各时点值之间存在相关性。混合效应模型可以充分利用信息，既可以分析随机效应和相关性，又能处理缺损值。