1、首都医科大学附属北京安贞医院 北京市心肺血管疾病研究所赵冬,1,如何写一份好的综述,2,写综述？,写综述？,3,综述的类型和特点,综述包括普通综述、系统综述和Meta分析：传统综述 是常见的综述形式，为某一主题的文献结果的总结，但有逐渐被系统综述取代的可能性。 系统综述是根据一定的入选标准, 系统地整理所有相关的 观察或实验研究的证据, 以回答一个特定的研究问题。特点为（1）目标明确，方法学清晰且可复制；（2）进行了系统化的文献检索，包括符合入选标准的所有文献；（3）对文献可靠性进行了评价；（4）综合包括的文献的特征和研究结果并给予系统的陈述。 Meta分析采用统计学的方法整合和总结所研究的文
2、献的结果。系统综述可以包括Meta分析，也可以不包括。Meta分析与一般的系统综述相比，可以对干预效果进行更加准确的估计。,(Cochrane Collaboration 的定义)www.cochrane-handbook.org,AbstractC-reactive protein (CRP) is a marker of systemic inflammation, and it has been implicated in the pathogenesis of many chronic diseases, including cardiovascular (CV) diseases.
3、With highly sensitive CRP assays, serum CRP can add considerably to standard coronary heart disease risk factors and in the prediction of subsequent major CV risk. We review evidence supporting the assessment of highly sensitive CRP both in patients with established CV diseases and in those without
4、known disease as well as evidence supporting CRP as a target of therapy. We also review various pharmacologic (especially intensive statin therapy) and nonpharmacologic therapies to reduce levels of CRP.,Am J Med Sci 2009 338:486-92,4,C-reactive protein and cardiovascular diseases-is it ready for pr
5、imetime?,Abstract OBJECTIVES: The goal of this systematic review is to assess the cross-sectional relationship of inflammatory markers with the presence and extent of coronary artery calcium (CAC) to identify asymptomatic individuals with a higher risk of coronary heart disease (CHD). BACKGROUND: Ma
6、rkers of subclinical inflammation and subclinical atherosclerosis have both been used to improve detection of individuals at high risk of developing cardiovascular disease. CAC has emerged as a surrogate maker for underlying coronary atherosclerosis, and has been shown to predict future CHD events.
7、Although inflammation is intimately associated with atherosclerosis, and levels of inflammatory markers predict cardiovascular risk, the relationship of subclinical inflammatory markers with the burden of coronary atherosclerosis is not clear. METHODS: Medline and Pub Med databases were searched for
8、 all studies assessing the relationship of inflammatory markers with CAC published till July 2007. RESULTS: We found 12 studies that met our criteria. CRP, fibrinogen, metallic metalloproteinase-9 (MMP-9), monocyte chemotactic protein 1 (MCP-1), resistin, lipoprotein-associated phospholipase A(2) (L
9、p-PLA(2), IL-6, tumor necrosis factor alpha (TNF-alpha) and beta-fibroblast growth factor (bFGF) were used as inflammatory markers. There was a wide variation among studies with regards to population size, inclusion criterias, age range and techniques. It was observed that in almost all studies the
10、relationship between inflammatory markers and CAC was weak, and was mostly found upon univariate analysis in women. However, this association was lost after correction for obesity and BMI. The data on the relationship of inflammation and CAC with progression of atherosclerosis is scarce and did not
11、show any predictive benefits for future CHD. CONCLUSION: Variable associations between CAC and inflammatory markers were identified. In most studies where a positive relationship was found, this relationship disappeared after appropriate correction for the presence of traditional risk factors. Our d
12、ata suggests that an approach in which inflammatory markers are used to further characterize risk in individuals with an established coronary artery disease burden is more warranted than using biomarkers as sole risk predictors of future CHD events. Large, well-planned comprehensive studies are requ
13、ired to identify the combined role of measuring inflammatory markers in assessment of atherosclerotic disease.,Atherosclerosis 2008 201:1-7,5,Markers of inflammation and coronary artery calcification: a systematic review.,Abstract BACKGROUND: Traditional risk factors do not explain all of the risk f
14、or incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD. PURPOSE: To summarize the results of 9 systematic reviews of novel risk factors to help the U.S. Preventive Services Task Force (USPSTF) evaluate the fa
15、ctors clinical usefulness. DATA SOURCES: Results from a MEDLINE search for English-language articles published from 1966 to September 2008, using the Medical Subject Heading terms cohort studies and cardiovascular diseases in combination with terms for each risk factor. STUDY SELECTION: Studies were
16、 included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors. DATA EXTRACTION: Study quality was evaluated by using USPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Gr
17、ading of Recommendations, Assessment, Development, and Evaluation framework. Each factors potential clinical value was evaluated by using a set of criteria that emphasized the importance of the effect of that factor on the reclassification of intermediate-risk persons. DATA SYNTHESIS: 9 systematic r
18、eviews were conducted. C-reactive protein (CRP) was the best candidate for use in screening and the most rigorously studied, but evidence that changes in CRP level lead to primary prevention of CHD events is inconclusive. The other evaluated risk factors were coronary artery calcium score as measure
19、d by electron-beam computed tomography, lipoprotein(a) level, homocysteine level, leukocyte count, fasting blood glucose, periodontal disease, ankle-brachial index, and carotid intima-media thickness. The availability and validity of the evidence varied considerably across the risk factors in terms
20、of aggregate quality, consistency of findings, and applicability to intermediate-risk persons in the general population. For most risk factors, no studies assessed their usefulness for reclassifying intermediate-risk persons. LIMITATIONS: Because of lack of access to original data, no firm conclusio
21、ns could be drawn about differences in risk prediction among racial and ethnic groups. The review did not emphasize within-cohort comparisons of multiple risk factors. CONCLUSION: The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of in
22、termediate-risk persons.,6,Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the U.S. Preventive Services Task Force.,7,Abstract OBJECTIVE: To assess the overall effects by a meta-analysis. DATA SOURCES: Electronic searches on PubMed and Ovid Medline fro
23、m their start to October 2009 were carried out. Objective Cohort studies and secondary analysis of randomised controlled trials reporting the relative risk (RR) of recurrent cardiovascular events or death associated with C-reactive protein (CRP) obtained within 72 h from acute coronary syndromes (AC
24、S) onset. DATA EXTRACTION: Two epidemiologists independently abstracted information on study design, study and participant characteristics, level of CRP, outcomes, control for potential confounding factors and risk estimates using a standardised form. RESULTS: A general variance-based method was use
25、d to pool the estimates of risk. Thirteen studies containing 1364 new cases identified from 9787 patients during the follow-up periods reported the risk estimates by CRP categories. Compared with the bottom CRP category (10 mg/l) category of CRP values with a random-effects model, respectively. Anot
26、her four and three studies reported the risk by unit of CRP or logarithmically transformed CRP. The pooled RRs (95% CI) were 1.49 (1.06 to 2.08) per 5 mg/l and 1.26 (0.95 to 1.69) per natural logarithm of CRP (mg/l), respectively. CONCLUSIONS: Greater early blood CRP moderately increases long-term r
27、isk of recurrent cardiovascular events or death, and may be a valuable prognostic predictor in patients after ACS.,Heart 2010 95:339-410,8,Early C-reactive protein in the prediction of long-term outcomes after acute coronary syndromes: a meta-analysis of longitudinal studies.,Abstract BACKGROUND: As
28、sociations of C-reactive protein (CRP) concentration with risk of major diseases can best be assessed by long-term prospective follow-up of large numbers of people. We assessed the associations of CRP concentration with risk of vascular and non-vascular outcomes under different circumstances. METHOD
29、S: We meta-analysed individual records of 160 309 people without a history of vascular disease (ie, 1.31 million person-years at risk, 27 769 fatal or non-fatal disease outcomes) from 54 long-term prospective studies. Within-study regression analyses were adjusted for within-person variation in risk
30、 factor levels. RESULTS: Log(e) CRP concentration was linearly associated with several conventional risk factors and inflammatory markers, and nearly log-linearly with the risk of ischaemic vascular disease and non-vascular mortality. Risk ratios (RRs) for coronary heart disease per 1-SD higher log(
31、e) CRP concentration (three-fold higher) were 1.63 (95% CI 1.51-1.76) when initially adjusted for age and sex only, and 1.37 (1.27-1.48) when adjusted further for conventional risk factors; 1.44 (1.32-1.57) and 1.27 (1.15-1.40) for ischaemic stroke; 1.71 (1.53-1.91) and 1.55 (1.37-1.76) for vascular
32、 mortality; and 1.55 (1.41-1.69) and 1.54 (1.40-1.68) for non-vascular mortality. RRs were largely unchanged after exclusion of smokers or initial follow-up. After further adjustment for fibrinogen, the corresponding RRs were 1.23 (1.07-1.42) for coronary heart disease; 1.32 (1.18-1.49) for ischaemi
33、c stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: CRP concentration has continuous associations with the risk of coronary heart disease, ischaemic stroke, vascular mortality, and death from several cancers and lung disease that are ea
34、ch of broadly similar size. The relevance of CRP to such a range of disorders is unclear. Associations with ischaemic vascular disease depend considerably on conventional risk factors and other markers of inflammation. FUNDING: British Heart Foundation, UK Medical Research Council, BUPA Foundation,
35、and GlaxoSmithKline. Copyright 2010 Elsevier Ltd. All rights reserved.,Lancet 2010 375:132-140,9,C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis.,10,不同类型文献的主要区别,传统文献综述的缺陷主观综合 缺乏标准化（可重复）的方法 注重统计学是否“有意义” 等价对待每篇文献，无权重 定
36、性而非定量,是准确、可靠总结研究证据的工具，帮助临床医生、研究人员和病人了解最新的研究现状；为政策制定者者判断比较诊断、干预或治疗方法的效果和危险提供依据；临床指南诊治制定的依据；杂志编辑判断投稿创新性的依据。,12,系统综述和Meta分析的功能,13,系统综述和Meta分析流程图,14,好综述的27条标准 PRISMA 菜单（ Preferred Reporting Items for Systematic reviews and Meta-Analyses),题目: 1项标准 摘要：1项标准 前言：2项标准 方法：12项标准 结果： 7项标准 讨论：3项标准 经费：1项标准,Alessan
37、dro Liberati et al Annals of Internal Medicine 2009;151:W65-w94,题目中应说明是系统综述或Meta分析举例：1.C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force.2.Markers of inflammation and coronary artery calcification: a syst
38、ematic review.,15,题目：1项标准,符合如下结构和内容： 背景 目标 资料来源 研究入选标准、研究人群和干预措施 评价和综合研究结果的方法 结果 局限性 结论和主要结果的意义 系统综述的注册号,16,摘要：1项标准,已现有知识为背景，说明了为什么要写本篇综述； 要综述的研究问题明确（符合PICOS标准）,17,前言：2项标准,P：研究对象（Participants)I: 干预措施 （Interventions)C: 对照 （Comparison)O: 结局 （Outcome)S: 研究设计 (Study design),18,PICOS标准：,提供标准化的综述方案（review
39、 protocol)，最好有注册号码* 入选标准明确合理 说明所有文献来源（文献数据库、其他文献来源） 文献检索的策略正确（说明局限性，如不可复制的检索方式）； 选择研究的标准合理； 有资料收集或摘录的程序（表格、独立性、获得原始数据的方法） 收集资料的内容（应列出所有采集的变量和定义） 应对个体研究内可能的偏倚进行评价； 合并的测量指标（如RR或均数差值） 结果合并的方法（统计学方法，如异质性检验、Meta分析的模型） 应对研究间的偏倚进行评价（如发表偏倚） 附加的分析方法（如敏感度分析、Meta回归分析）,19,方法学：12项标准,发表偏倚（publication bias） 定位偏倚（l
40、ocation biases） 引用偏倚（citation bias） 多次发表偏倚（multiple publication bias） 入选标准偏倚（biased inclusion criteria）,偏倚的种类,定义具有统计学显著性意义的研究结果较无显著性意义和无效的结果被报告和发表的可能性更大。,发表偏倚,在已发表的研究中，阳性结果的文章更容易以英文发表在国际性杂志，同时不同数据库之间的收录差异，可能带来文献定位中的偏倚。英语偏倚（English language bias） 文献库偏倚（Database bias）,定位偏倚,一项研究结果发表在不同的杂志上，导致重复引用。,多次发表
41、偏倚,漏斗图 相对于样本量的效应值，是以研究的效应估计值作为横坐标，样本量作为纵坐标画出的散点图 漏斗图分析 根据图形的不对称程度判断系统综述或Meta分析中有无偏倚,漏斗图分析,针灸治疗中风的49个试验的漏斗图分析 （Tang TL, 1999）,如果Meta分析中没有偏倚，图形构成一个对称的倒置“漏斗”；如果图形呈现明显的不对称，表明偏倚可能存在,样本量小的研究结果通常分散在图形底部很宽的范围内,样本量大的研究结果集中在图形上部一个较窄的范围内,Meta分析中异质性资料处理的方法,被选择研究的详细情况（筛选的数量、符合入选条件的、最终选择的数量、每一阶段被排除研究的排除原因、最好有流程图）
42、* 细述入选研究的特征（包括样本大小、PICOS、随访时间）和引证； 入选各个研究可能存在的偏倚（如结局定义） 列出各个研究的结果（如森林图）*； 合并计算的结果（包括Meta分析的结果，可信区间和异质性检验） 研究间可能存在的出现偏倚的危险评估 附加分析的结果（如敏感度分析）,27,结果：7项标准,Health Technol Assess. 2006 Oct;10(39):iii-iv, ix-x, 1-41,主要结果的证据强度进行总结，陈述结果可能的价值； 要研究的局限性和可能存在的偏倚（从研究的水平和综述的水平） 做出总的结论和今后研究的方向,29,讨论：3项标准,本综述的资助来源。,30,经费：1项标准,方积乾：生物医学研究的统计学方法（高等教育出版社）王家良：临床流行病学（上海科学技术出版社）Stephen B. Hulley: Designing Clinical Research (Third edition,2007 )Cochrane Collaboration: www.cochrane-handbook.org CRD guideline: www.york.ac.uk,31,推荐阅读的工具书和文献及网站,
