bph的循证治疗董碧蓉南宁

1、bph的循证治疗的循证治疗evidence-based therapy of bph 中国循证医学中心中国循证医学中心 临床流行病学研究室临床流行病学研究室老年科老年科董碧蓉教授博士生导师一一.临床治疗依据的演变临床治疗依据的演变1900s个人经验个人经验权威性教学权威性教学无对照病例报告无对照病例报告病例对照研究病例对照研究, , 临床试验临床试验以科学为本的病因学以科学为本的病因学1970s临床终点指标研究临床终点指标研究+ + 临床经验临床经验以证据为本的临床用药以证据为本的临床用药1995医药费用直线攀医药费用直线攀升！升！ 卫生服务需求卫生服务需求不断增加！不断增加！卫生资源利卫生资

2、源利用不均！用不均！医患关系医患关系紧张！紧张！the rate of radical prostatectomy per 100,000 male medicare beneficiaries, adjusted for age and race手术率范围差异令人难以手术率范围差异令人难以置信：置信：20/100,000 in rhode 20/100,000 in rhode 429/100,000 in alaska 429/100,000 in alaska 21:1 21:1有些州经历太多的手术，许多病人阳萎和失禁相反，有些州手术不足合理的治疗可能存在于两极端之间。“keep the

3、 balance between benefits and harms”临床决策临床决策临床关于临床关于bph的治疗问题很多的治疗问题很多干预类型的选择干预类型的选择内科药物治疗内科药物治疗l -受体阻滞剂受体阻滞剂外科治疗外科治疗用药时机？用药时机？单药单药/联合？联合？用药疗程？用药疗程？不良事件？不良事件？药物相互作用药物相互作用?what is the evidence-based practice（ebp) 整合病人价值，临床医生的专业技能和最好证据，将三者完美地结合以制定出患者的治疗措施 sackett dl 2001model of evidence based clinical

4、 decisions clinical circumstancespatient preference research evidence clinical expertise 临床医生将专业技能，整合证据，同时考虑病人意愿与价值，与病人及家属进行沟通，然后协助做出决策的能力。 1. 1.临床经验临床经验（clinical expertise） l进行医学实践活动的基本能力：问诊、查体、进行医学实践活动的基本能力：问诊、查体、与病人沟通的能力与病人沟通的能力l对疾病病理生理、解剖知识的了解（专业知对疾病病理生理、解剖知识的了解（专业知识）识）l临床个人经验的积累临床个人经验的积累 尿道尿道移行

5、移行带（增生发带（增生发 生部分）生部分）中央区（癌发生部分）中央区（癌发生部分） 外周带外周带bphbph从从移行移行带带发生发生（benign prostatic hyperplasia， bph）解剖知识解剖知识development of bph : early slide 1 of 3bph的发生（早期）的发生（早期）膀胱膀胱包绕前列腺包绕前列腺上分的肌肉上分的肌肉前列腺前列腺组织组织外科外科包膜包膜前列腺段尿道前列腺段尿道development of bph : intermediate slide 2 of 3bph的发生（中期）的发生（中期）前列腺前列腺组织组织外科外科包膜包膜

6、狭窄的前列腺狭窄的前列腺段尿道段尿道development of bph : late slide 3 of 3严重狭窄的前严重狭窄的前列腺段尿道列腺段尿道bph的发生（晚期）的发生（晚期）前列腺前列腺组织组织外科外科包膜包膜40-7940-79岁每岁每年增长年增长0.6ml0.6ml，2020年后体年后体积增加积增加12ml12ml如果原来体如果原来体积是积是20ml20ml,20,20年后体积会年后体积会达到达到32ml32ml 前列腺的体积与年龄有关前列腺的体积与年龄有关生理知识生理知识前列腺增生症的发病率随年龄前列腺增生症的发病率随年龄增长而明显增加增长而明显增加流行病学知识流行病学知

7、识definition of termsnlutslower-urinary-tract symptomsnbpebenign prostatic enlargement(macroscopic)nboobladder-outlet obstructionnbphbenign prostatic hyperplasia (microscopic/histologic)nbpobenign prostatic obstruction (boo caused by bpe)nclinical bph luts + bpe + boo slide i.1病理生理知识病理生理知识adapted fro

8、m nordling j et al. in benign prostatic hyperplasia. plymouth, united kingdom: health publication, 2001:107-166.pathophysiology of clinical bph:overlapping but independent featuresslide i.2lutsenlargedprostateboo病理生理知识病理生理知识pathophysiology of clinical bph:predictive risk factorsslide i.4nincreasing

9、agenprostatic enlargementnelevated prostate-specific antigen (psa)nlower-urinary-tract symptoms (luts)ndecreased urinary flow rate bph的临床表现特点的临床表现特点排尿期症状排尿期症状(梗阻性梗阻性,占占25%)l排尿费力排尿费力,尿不尽感尿不尽感l尿线细慢尿线细慢l尿流中断尿流中断白天晚上储尿期症状储尿期症状(刺激性刺激性,占占25%)l尿频尿频(排尿次数增加排尿次数增加)l尿急尿急l夜尿增加夜尿增加储尿期 + 排尿期症状占50%日夜不轻松膀胱憩室膀胱憩室上尿路

10、积水上尿路积水尿潴留尿潴留前列腺增生的危害性前列腺增生的危害性尿路感染尿路感染膀胱结石膀胱结石血尿血尿腹股沟疝、脱肛、痔疮腹股沟疝、脱肛、痔疮反复起夜，影响休息，反复起夜，影响休息，诱发心脑血管疾病发作诱发心脑血管疾病发作前列腺容积和前列腺容积和lutslutsn前列腺容积对生活质量的影响前列腺容积对生活质量的影响 30ml 30ml 是是 30ml 40ml 40ml 是是 40ml 50ml 50ml 是是 50ml 50ml 的的 3.5 3.5 倍倍n中到重度症状影响中到重度症状影响qolqol是无症状的是无症状的4-64-6倍倍国际前列腺症状评分表国际前列腺症状评分表(ipss)(i

11、pss)0-7分分=轻度；轻度； 8-19分分=中度；中度； 20-35分分=重度重度2.2.最佳临床研究证据最佳临床研究证据（the best evidence)指与临床密切相关的研究，以人体研究证据指与临床密切相关的研究，以人体研究证据证据的级别的证据的级别的“金字塔金字塔”寻求寻求 poemspoems，避免，避免doesdoes q熟悉如何寻找临床问题的答案是重要的技能熟悉如何寻找临床问题的答案是重要的技能qpoem:patient-oriented evidence that mattersn 病人为中心的测量指标病人为中心的测量指标 （终点指标）（终点指标）ndoe：disease

12、-oriented evidence”n常引起误导，通常不成熟常引起误导，通常不成熟bphbph的治疗目标的治疗目标终点指标终点指标n生活质量生活质量 nauraur发生率发生率n前列腺手术率前列腺手术率n不良反应发生率不良反应发生率 n保护膀胱功能保护膀胱功能 中间指标改善中间指标改善n尿流率尿流率n残余尿残余尿n症状症状n前列腺体积前列腺体积1010年前观点年前观点目前观点目前观点源于对源于对9090种杂志持续种杂志持续6 6个月的个月的调查显示：调查显示：l97%97%的文献是的文献是doesdoes或其他。或其他。l80478047篇文献中仅篇文献中仅213213篇（篇（2.6%) 2

13、.6%) 是是poemspoems如何寻找高质量证据如何寻找高质量证据? ?ltextbook (print or online)lmedline or pubmed search: find and review articleslpre-appraised evidence best evidence clinical evidence (therapy only) cochrane collaboration (therapy only) uptodate循证教科书要求循证教科书要求使用超文本（使用超文本（hyepertext, pda) 的电子图书的电子图书收入的知识须是源于当前最好的

14、研究证据收入的知识须是源于当前最好的研究证据每一项证据都有质量评级每一项证据都有质量评级随着新证据的出现不断更新随着新证据的出现不断更新通过互联网传送给每一个医生和决策人员通过互联网传送给每一个医生和决策人员.推荐教科书推荐教科书clinical evidence (the bmj publishing group and the american college of physicians 1999 年第年第1次出版次出版)evidence-based on call (cd)harrisons textbooks(cd)merck manualebcp data resources qsu

15、mmaries of the primary evidenceacp journal club | clinical evidence | emedicine | fpin clinical inquiries | infopoems| uptodateqdatabasesmedline | cochrane libraryqelectronic textbooks and librariesacp medicine | harrisons | md consult | stat!ref qmeta-search enginessumsearch | trip plus: turning re

16、search into practice点击点击双击双击点击点击clincial trial 132other reviews 3评价证据评价证据evaluating the validity of the studyn对每一个研究必须回答三个基本问题对每一个研究必须回答三个基本问题 there are three basic questions that need to be answered for every type of study: l 研究结果的真实性如何？研究结果的真实性如何？are the results of the study valid? l 临床意义和统计学意义临床意

17、义和统计学意义what are the results? l 结果有助于我处理病人吗？结果有助于我处理病人吗？will the results help in caring for my patient?评价方式评价方式n自己进行文献评价自己进行文献评价 critically appraise articles yourselfn借助已评价的证据资源借助已评价的证据资源used a source that appraises trials for youlbest evidencelclinical evidence lcochrane libraryluptodatediagnosis of

18、 clinical bph: international recommendationsslide iv.1assessment icbph guidelinesquantification of symptomsipssrecommendedquantification of symptomsbother scorerecommendeddigital rectal examinationrecommendedurinalysis recommendedpsa measurementrecommendedvoiding diary (frequency-volume charts)recom

19、mendedurinary flow-rate recordingoptionalpostvoid residual urine volume studiesoptionalpressure-flow studiesoptionalprostate imaging (trus)optionalupper-urinary-tract imaging (us or ivu)optionallower-urinary-tract endoscopyoptionalserum creatinine measurementnot recommendedadapted from fifth interna

20、tional consultation 2001 on bph. in benign prostatic hyperplasia. plymouth, united kingdom: health publication, 2001:519-535.bph的治疗目标的治疗目标icbph制定的制定的bph的治疗目标：的治疗目标：l缩小前列腺体积和缩小前列腺体积和/ /或减轻梗阻或减轻梗阻l防止远期并发症防止远期并发症4 4l缓解临床症状缓解临床症状4 44.evaluation and treatment of low urinary tract symptoms in older man. 2

21、001 5th international consultation on bph. recommendation of the international scientific committeeevidence-based medicine:proven treatment for clinical bphnevidence-based medicine is based on results of clinical research.ndrugs in the same therapeutic class may exert different pharmacologic effects

22、.nindependent clinical studies must establish each drugs efficacy, safety, and effect on outcomes. noutcome studies with drugs for clinical bph should evaluate the effects of therapy on aur and bph-related surgery.slide v.1proscar:durable efficacy in long-term trialsdurationlong-term improvementstud

23、y(years)symptoms prostate volume urinary flownorth american1 scarp2 prospect2 prowess2 pless4 north american extension* maintainedmaintainedmaintainedscandinavian open extension* maintainedmaintainedmaintainedslide v.4 = significant improvement from baseline vs. placebo (p0.05); scarp = scandinavian

24、 study of reduction of the prostate; prospect = proscar safety plus efficacy canadian two-year study; prowess = proscar worldwide efficacy and safety study; pless = proscar long-term efficacy and safety study*benefits achieved during double-blind therapy were maintained in extensions.治疗组治疗组对照组对照组保列治

25、保列治 治疗对前列腺体积的影响治疗对前列腺体积的影响effects of proscar on the natural history of clinical bph: reduced risk of aurslide v.5placeboproscar57%riskreductionp0.00115105041230probability of auryears no. of aurs36252018 no. at risk1503145413981347 no. of aurs1411710 no. at risk1513148714491421placeboproscarp0.001 a

26、t 4 years proscar vs. placeboadapted from mcconnell jd et al n engl j med 1998;338(9):557-563. effects of proscar on the natural history of clinical bph: reduced risk of surgeryslide v.655%riskreductionp0.0011510501230probability of surgeryno. of surgeries37523231no. at risk1503145413741314no. of su

27、rgeries1822920no. at risk1513148314381410years4placeboproscarplaceboproscarp0.001 at 4 years, proscar vs. placeboadapted from mcconnell jd et al n engl j med 1998;338(9):557-563. effect of proscar on the natural history of bph: relative risk reductions vs. interventions in other diseasesriskconditio

28、noutcomeintervention reduction (%)osteoporosisvertebral fracturealendronate4447hip fracture alendronate 2151atherosclerosisptca or cabgstatins1737 fatal/nonfatal mi statins 2540epilepsyseizuresanticonvulsants3887superficial bladder cancer recurrencebcg + surgery3180kidney stonesrecurrencepharmacothe

29、rapy6380bphaurproscar57surgery proscar 55slide v.7ptca = percutaneous transluminal coronary angioplasty; cabg = coronary artery bypass graft; bcg = bacillus calmette-gurinadapted from roehrborn cg et al urology 2000;56:9-18. mcconnell et al n eng j med 1998;338(9):557-563.psa and proscarnpredictably

30、 reduces psa by 50% in men with bph nmultiplication of psa values by 2 in men treated for 6 months preserves predictive value of psa measurements slide v.8in pless, proscar did not mask prostate cancer detected by psalong-term experiencewith proscarnsustained improvements over 7 years of therapynred

31、uctions in symptom scoresnsustained reductions in prostate volume 25% reduction at year 7nsustained increases in urinary flow 2.5 ml/sec increase at year 7nconsistent safety and tolerability profile over 8 years of therapyslide vi.1data on file, msd. rapid and sustained reduction in the risk of long

32、-term outcomes with proscardouble-blind study open-label extensionslide vi.3n values indicate number of patients completing each trial phaseadapted from roehrborn cg et al. poster 419.placebo (n=1503)proscar 5 mg (n=1513)placebo proscar 5 mg (n=858)proscar 5 mg proscar 5 mg (n=979)543210yearly % of aur and/or bph-related surgery123456study year3.71.94.42.13.31.03.02.01.00.71.41.3slide vi.4 *p0.05 proscar vs. placebo at every time point after 4 months to 1 year and p0.001 proscar vs. placebo every 4 months, years 1 to 4*significa