bph的循证治疗-董碧蓉-南宁

1、BPH的循证治疗Evidence-Based therapy of BPH,中国循证医学中心 临床流行病学研究室 老年科,董碧蓉,教授 博士生导师,一.临床治疗依据的演变,个人经验,权威性教学,无对照病例报告,临床终点指标研究+ 临床经验,以证据为本的临床用药,医药费用直线攀升！,卫生服务需求不断增加！,卫生资源利用不均！,医患关系紧张！,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置信： 20/100,000 in

2、 Rhode 429/100,000 in Alaska 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 balance between benefits and harms”,临床决策,临床关于BPH的治疗问题很多,干预类型的选择,内科药物治疗,-受体阻滞剂 5-还原酶抑制剂 中药和植物制剂,外科治疗,用药时机？ 单药/联合？ 用药疗程？ 不良事件？ 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

3、出患者的治疗措施,Integrating patient values, clinical expertise and best evidence, Sackett DL 2001,Model of evidence based clinical decisions,clinical circumstances patient 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.临床经验（clinical expertise）,进行医学实践活动的

4、基本能力：问诊、查体、与病人沟通的能力 对疾病病理生理、解剖知识的了解（专业知识） 临床个人经验的积累,尿道,移行带（增生发 生部分）,中央区（癌发生部分）,外周带,BPH从移行带发生（Benign Prostatic Hyperplasia， BPH）,解剖知识,Development of BPH : Early,Slide 1 of 3,BPH的发生（早期）,膀胱,包绕前列腺 上分的肌肉,前列腺组织,外科包膜,前列腺段尿道,Development of BPH : Intermediate,Slide 2 of 3,BPH的发生（中期）,前列腺组织,外科包膜,狭窄的前列腺段尿道,Deve

5、lopment of BPH : Late,Slide 3 of 3,严重狭窄的前列腺段尿道,BPH的发生（晚期）,前列腺组织,外科包膜,40-79岁每年增长0.6ml，20年后体积增加12ml 如果原来体积是20ml,20年后体积会达到32ml,前列腺的体积与年龄有关,生理知识,前列腺增生症的发病率随年龄增长而明显增加,流行病学知识,Definition of Terms,LUTSLower-urinary-tract symptoms BPEBenign prostatic enlargement(macroscopic) BOOBladder-outlet obstruction BPH

6、Benign prostatic hyperplasia (microscopic/histologic) BPOBenign prostatic obstruction (BOO caused by BPE) Clinical BPH LUTS + BPE + BOO,Slide I.1,病理生理知识,Adapted from Nordling J et al. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:107-166.,Pathophysiology of Clin

7、ical BPH:Overlapping but Independent Features,Slide I.2,病理生理知识,Pathophysiology of Clinical BPH:Predictive Risk Factors,Slide I.4,Increasing age Prostatic enlargement Elevated prostate-specific antigen (PSA) Lower-urinary-tract symptoms (LUTS) Decreased urinary flow rate,BPH的临床表现特点,排尿期症状(梗阻性,占25%) 排尿

8、费力,尿不尽感 尿线细慢 尿流中断,白天,晚上,储尿期症状(刺激性,占25%) 尿频(排尿次数增加) 尿急 夜尿增加,储尿期 + 排尿期症状占50%,日夜不轻松,膀胱憩室,上尿路积水,尿潴留,前列腺增生的危害性,尿路感染,膀胱结石,血尿,腹股沟疝、脱肛、痔疮,反复起夜，影响休息， 诱发心脑血管疾病发作,前列腺容积和LUTS,前列腺容积对生活质量的影响 30ml 是 40ml 是 50ml 是 50ml 的 3.5 倍 中到重度症状影响QoL是无症状的4-6倍,国际前列腺症状评分表(IPSS),0-7分=轻度； 8-19分=中度； 20-35分=重度,2.最佳临床研究证据（The best ev

9、idence),指与临床密切相关的研究，以人体研究证据,设计良好的临床研究才是让证据说话的基石 随机对照试验是防治性研究的金标准 将来有可能有新的证据出现,证据的级别的“金字塔”,临床研究证据分级,寻求 POEMs，避免DOEs,熟悉如何寻找临床问题的答案是重要的技能 POEM:Patient-Oriented Evidence that Matters 病人为中心的测量指标 （终点指标） DOE：Disease-Oriented Evidence” 常引起误导，通常不成熟,BPH的治疗目标,终点指标 生活质量 AUR发生率 前列腺手术率 不良反应发生率 保护膀胱功能,中间指标改善 尿流率 残

10、余尿 症状 前列腺体积,10年前观点,目前观点,源于对90种杂志持续6个月的调查显示：,97%的文献是DOEs或其他。 8047篇文献中仅213篇（2.6%) 是POEMs,如何寻找高质量证据?,Textbook (print or online) Medline or PubMed search: find and review articles Pre-appraised evidence Best Evidence Clinical Evidence (Therapy only) Cochrane Collaboration (Therapy only) UpToDate,循证教科书要求

11、,使用超文本（hyepertext, PDA) 的电子图书 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 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.,推荐教科书,Clinical Evidence (the BMJ Publishing Group and the American College of Physicians 1999 年第1次出版) Evidence-Based on Call (CD) Harrisons textbooks(CD) Merck Manual,EBCP DATA Resources,Summaries of the pr

12、imary evidenceACP Journal Club | Clinical Evidence | eMedicine | FPIN Clinical Inquiries | InfoPOEMs| UpToDate DatabasesMEDLINE | Cochrane Library Electronic textbooks and librariesACP Medicine | Harrisons | MD Consult | Stat!Ref Meta-Search EnginesSUMSearch | TRIP Plus: Turning Research into Practi

13、ce,点击,点击,双击,双击,点击,点击,Clincial Trial 132,Other Reviews 3,评价证据Evaluating the Validity of The Study,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: 研究结果的真实性如何？Are the results of the study valid? 临床意义和统计学意义What are the results? 结果有助于我处理病人吗？Will the resu

14、lts help in caring for my patient?,评价方式,自己进行文献评价 Critically appraise articles yourself 借助已评价的证据资源Used a source that appraises trials for you Best Evidence Clinical Evidence Cochrane Library UpToDate,Diagnosis of Clinical BPH: International Recommendations,Slide IV.1,Assessment ICBPH Guidelines Quant

15、ification of symptomsIPSSRecommended Quantification of symptomsbother scoreRecommended Digital rectal examinationRecommended Urinalysis Recommended PSA measurementRecommended Voiding diary (frequency-volume charts)Recommended Urinary flow-rate recordingOptional Postvoid residual urine volume studies

16、Optional Pressure-flow studiesOptional Prostate imaging (TRUS)Optional Upper-urinary-tract imaging (US or IVU)Optional Lower-urinary-tract endoscopyOptional Serum creatinine measurementNot recommended,Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymout

17、h, United Kingdom: Health Publication, 2001:519-535.,BPH的治疗目标,ICBPH制定的BPH的治疗目标： 缩小前列腺体积和/或减轻梗阻 防止远期并发症4 缓解临床症状4,4.Evaluation and treatment of low urinary tract symptoms in older man. 2001 5th international consultation on BPH. Recommendation of the international scientific committee,Evidence-Based M

18、edicine:Proven treatment for Clinical BPH,Evidence-based medicine is based on results of clinical research. Drugs in the same therapeutic class may exert different pharmacologic effects. Independent clinical studies must establish each drugs efficacy, safety, and effect on outcomes. Outcome studies

19、with drugs for clinical BPH should evaluate the effects of therapy on AUR and BPH-related surgery.,Slide V.1,PROSCAR:Durable Efficacy in Long-Term Trials,DurationLong-Term Improvement Study(years)SymptomsProstate VolumeUrinary Flow North American1 SCARP2 PROSPECT2 PROWESS2 PLESS4 North American Exte

20、nsion* MaintainedMaintainedMaintained Scandinavian Open Extension*MaintainedMaintainedMaintained,Slide V.4, = significant improvement from baseline vs. placebo (p0.05); SCARP = Scandinavian Study of Reduction of the Prostate; PROSPECT = Proscar Safety Plus Efficacy Canadian Two-Year Study; PROWESS =

21、 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,对照组,保列治治疗对前列腺体积的影响,Effects of PROSCAR on the Natural History of Clinical BPH: Reduced Risk of AUR,Slide V.5,Placebo,PROS

22、CAR,57% risk reduction p0.001,4,1,2,3,0,Probability of AUR,Years,No. of AURs36252018 No. at risk1503145413981347 No. of AURs1411710 No. at risk1513148714491421,Placebo PROSCAR,p0.001 at 4 years PROSCAR vs. placebo Adapted from McConnell JD et al N Engl J Med 1998;338(9):557-563.,Effects of PROSCAR o

23、n the Natural History of Clinical BPH: Reduced Risk of Surgery,Slide V.6,15,10,5,0,1,2,3,0,Probability of surgery,No. of surgeries37523231 No. at risk1503145413741314 No. of surgeries1822920 No. at risk1513148314381410,Years,4,Placebo,PROSCAR,Placebo PROSCAR,p0.001 at 4 years, PROSCAR vs. placebo Ad

24、apted 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 Diseases,RiskConditionOutcomeInterventionReduction (%) OsteoporosisVertebral fractureAlendronate4447Hip fracture Alendronate 2151 Ather

25、osclerosisPTCA or CABGStatins1737 Fatal/nonfatal MI Statins 2540 EpilepsySeizuresAnticonvulsants3887 Superficial bladder cancer RecurrenceBCG + surgery3180 Kidney stonesRecurrencePharmacotherapy6380 BPHAURPROSCAR57Surgery PROSCAR 55,Slide V.7,PTCA = percutaneous transluminal coronary angioplasty; CA

26、BG = coronary artery bypass graft; BCG = bacillus Calmette-Gurin Adapted from Roehrborn CG et al Urology 2000;56:9-18. McConnell et al N Eng J Med 1998;338(9):557-563.,PSA and PROSCAR,Predictably reduces PSA by 50% in men with BPH Multiplication of PSA values by 2 in men treated for 6 months preserv

27、es predictive value of PSA measurements,Slide V.8,In PLESS, PROSCAR did not mask prostate cancer detected by PSA,Long-Term Experiencewith PROSCAR,Sustained improvements over 7 years of therapy Reductions in symptom scores Sustained reductions in prostate volume 25% reduction at year 7 Sustained incr

28、eases in urinary flow 2.5 ml/sec increase at year 7 Consistent safety and tolerability profile over 8 years of therapy,Slide VI.1,Data on file, MSD.,Rapid and Sustained Reduction in the Risk of Long-Term Outcomes with PROSCAR,Double-blind studyOpen-label extension,Slide VI.3,n values indicate number

29、 of patients completing each trial phase Adapted 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),Yearly % of AUR and/or BPH-related surgery,1,2,3,4,5,6,Study year,3.7,1.9,4.4,2.1,3.3,1.0,3.0,2.0,1.0,0.7,1.4,1.3,

30、Slide 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*Significant improvement vs. baseline with PROSCAR and placebo at 4 years, p0.001 PSA = prostate-specific antigen Adapted from Bruskewitz R et al Urology 1999

31、;54:670-678.,Overallbother score*,*,By baseline PSA tertile (ng/ml),PSA: 012,PSA: 01.3,PSA: 1.43.2,PSA: 3.312,1234,1234,1234,1234,Year of follow-up,0 1 2 3 4,Mean (SE) change inbother score from baseline,PROSCAR Significantly Reduced Bother Over Long-Term Therapy (4 Years) (PLESS Substudy),联合治疗的理论基础,From evidences(MTOPS)and synte