如何写好系统综述.ppt

现在学习的是第1页，共31页2写综述？ 写综述？ 现在学习的是第2页，共31页3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现在学习的是第3页，共31页4AbstractAbstract C-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. 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 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.现在学习的是第4页，共31页5AbstractAbstractOBJECTIVES: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:BACKGROUND: Markers 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. 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. METHODS: Medline and Pub Med databases were searched for all studies assessing the relationship of inflammatory markers with CAC published till July 2007. RESULTS:. 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) (Lp-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 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 show any predictive benefits for future CHD. CONCLUSION: . 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 data 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 required to identify the combined role of measuring inflammatory markers in assessment of atherosclerotic disease.现在学习的是第5页，共31页6AbstractAbstractBACKGROUND:BACKGROUND: Traditional risk factors do not explain all of the risk for incident coronary heart disease (CHD) events. Various new or emerging risk factors have the potential to improve global risk assessment for CHD. PURPOSE: 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 factors 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:STUDY SELECTION: Studies were included if the participants had no baseline cardiovascular disease and the investigators adjusted for at least 6 Framingham risk factors. DATA EXTRACTION:. DATA EXTRACTION: Study quality was evaluated by using USPSTF cUSPSTF criteria and overall quality of evidence for each risk factor by using a modified version of the Grading 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: DATA SYNTHESIS: 9 systematic reviews 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 measured 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 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:LIMITATIONS: Because of lack of access to original data, no firm conclusions 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. CONCLUSION: The current evidence does not support the routine use of any of the 9 risk factors for further risk stratification of intermediate-risk persons.现在学习的是第6页，共31页7现在学习的是第7页，共31页8AbstractAbstractOBJECTIVE:OBJECTIVE: To assess the overall effects by a meta-analysis. DATA SOURCES: Electronic searches on PubMed and Ovid Medline from 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 (ACS) onset. DATA EXTRACTION: 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: RESULTS: A general variance-based method was used 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. Another 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: CONCLUSIONS: Greater early blood CRP moderately increases long-term risk of recurrent cardiovascular events or death, and may be a valuable prognostic predictor in patients after ACS.现在学习的是第8页，共31页9AbstractAbstractBACKGROUND:BACKGROUND: Associations 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. METHODS: METHODS: 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 factor levels. RESULTS: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(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 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 ischaemic stroke; 1.34 (1.18-1.52) for vascular mortality; and 1.34 (1.20-1.50) for non-vascular mortality. INTERPRETATION: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 each 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, and GlaxoSmithKline. Copyright 2010 Elsevier Ltd. All rights reserved.现在学习的是第9页，共31页10 论著论著普通综述普通综述系统综述系统综述MetaMeta分析分析数据基础一次文献二次或三次文献二次文献一次或二次文献文献检索无特定标准无特定标准一定时间内所有发表的文献一定时间内所有发表的文献研究方法 有特定要求无特定要求有特定要求有特定要求研究结果基于原始数据分析定性总结对文献研究结果的定性或定量综合和陈述文献研究数据定量综合和陈述讨论有无有有客观质量评价标准有无有有现在学习的是第10页，共31页传统文献综述的缺陷传统文献综述的缺陷u主观综合主观综合u缺乏标准化（可重复）的方法缺乏标准化（可重复）的方法u注重统计学是否注重统计学是否“有意义有意义”u等价对待每篇文献，无权重等价对待每篇文献，无权重u定性而非定量定性而非定量现在学习的是第11页，共31页12u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；u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；u临床指南诊治制定的依据；u杂志编辑判断投稿创新性的依据。现在学习的是第12页，共31页13经文献检索数据库查到的文献篇数 其他来源的文献篇数去除重复的文献后的篇数去除重复的文献后的篇数参加筛选的文献的篇数（摘要）参加筛选的文献的篇数（摘要）排除的篇数排除的篇数 符合要求的文献的篇数（全文）符合要求的文献的篇数（全文）定性分析综述的研究数量定性分析综述的研究数量 排除的文献（全文）和排除的排除的文献（全文）和排除的理由理由定量分析的研究数量定量分析的研究数量(meta-analysis)系统综述和Meta分析流程图现在学习的是第13页，共31页14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Alessandro Liberati et al Annals of Internal Medicine 2009;151:W65-w94 现在学习的是第14页，共31页15题目中应说明是系统综述或题目中应说明是系统综述或MetaMeta分析分析举例：1.C-reactive protein as a risk factor for coronary heart disease1.C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-: a systematic review and meta-analyses for the U.S. Preventive Services Task Force.analyses for the U.S. Preventive Services Task Force.2.Markers of inflammation and coronary artery calcification: 2.Markers of inflammation and coronary artery calcification: a systematic review.a systematic review.现在学习的是第15页，共31页16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现在学习的是第16页，共31页17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）现在学习的是第17页，共31页18 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)现在学习的是第18页，共31页19提供标准化的综述方案（review 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） 现在学习的是第19页，共31页发表偏倚（发表偏倚（publication bias） 定位偏倚（定位偏倚（location biases） 引用偏倚（引用偏倚（citation bias） 多次发表偏倚（多次发表偏倚（multiple publication bias） 入选标准偏倚（入选标准偏倚（biased inclusion criteria） 偏倚的种类现在学习的是第20页，共31页 定义定义 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。无效的结果被报告和发表的可能性更大。 发表偏倚现在学习的是第21页，共31页 在已发表的研究中，阳性结果的文章更容易以英文发在已发表的研究中，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。带来文献定位中的偏倚。英语偏倚（英语偏倚（English language bias）文献库偏倚（文献库偏倚（Database bias）定位偏倚现在学习的是第22页，共31页 一项研究结果发表在不同的杂志上，导致重复引一项研究结果发表在不同的杂志上，导致重复引用。用。多次发表偏倚现在学习的是第23页，共31页漏斗图漏斗图 相对于样本量的效应值，是以研究的效应估计值作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为横坐标，样本量作为纵坐标画出的散点图漏斗图分析漏斗图分析 根据图形的不对称程度判断系统综述或根据图形的不对称程度判断系统综述或MetaMeta分析中有无偏倚分析中有无偏倚 漏斗图分析现在学习的是第24页，共31页如果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现在学习的是第25页，共31页异质性的处理忽略异质性检验异质性合并解释固定效应模型有异质性不合并随机效应模型亚组分析Meta回归Meta分析中异质性资料处理的方法现在学习的是第26页，共31页27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）*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）现在学习的是第27页，共31页Health Technol Assess. 2006 Oct;10(39):iii-iv, ix-x, 1-41现在学习的是第28页，共31页29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现在学习的是第29页，共31页30本综述的资助来源。现在学习的是第30页，共31页感谢大家观看感谢大家观看现在学习的是第31页，共31页