bph的循证治疗课件

1、bph的循证治疗,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,bph的循证治疗,3,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

2、以置信： 20/100,000 in 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,bph的循证治疗,5,Keep the balance between benefits and harms,临床决策,bph的循证治疗,6,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,bph的循证治疗,7,What is the Evidence-based P

3、ractice（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,Integrating patient values, clinical expertise and best evidence,Sackett DL 2001,bph的循证治疗,8,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

4、属进行沟通，然后协助做出决策的能力,bph的循证治疗,9,1.临床经验（clinical expertise,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 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,bph的循证治疗,11,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,bph的循证治疗,12

5、,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,bph的循证治疗,13,Development 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,bph的循证治疗,14,40-79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,bph的循证治疗,15,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

6、 Terms,LUTSLower-urinary-tract symptoms BPEBenign prostatic enlargement(macroscopic) BOOBladder-outlet obstruction BPHBenign 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

7、. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:107-166,Pathophysiology of Clinical 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

8、-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,bph的循证治疗,20,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,bph的循证治疗,21,前列腺容积和LU

9、TS,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,bph的循证治疗,22,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,bph的循证治疗,23,2.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,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,bph的循证治疗,24,证据的级别的“金字塔,临床研究证据分级,bph的循证治疗,25,寻求 POEMs，避免DOEs,

10、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的循证治疗,26,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 残余尿 症状 前列腺体积,10年前观点,目前观点,bph的循证治疗,27,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,bph的循

11、证治疗,28,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,bph的循证治疗,29,循证教科书要求,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

12、不断更新 通过互联网传送给每一个医生和决策人员,bph的循证治疗,30,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,bph的循证治疗,31,EBCP DATA Resources,Summaries of the primary evidenceACP Journal Club | Clinical Evid

13、ence | 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 Practice,bph的循证治疗,32,点击,点击,bph的循证治疗,33,双击,bph的循证治疗,3

14、4,bph的循证治疗,35,bph的循证治疗,36,bph的循证治疗,37,bph的循证治疗,38,bph的循证治疗,39,bph的循证治疗,40,bph的循证治疗,41,bph的循证治疗,42,bph的循证治疗,43,双击,bph的循证治疗,44,点击,bph的循证治疗,45,bph的循证治疗,46,点击,bph的循证治疗,47,bph的循证治疗,48,Clincial Trial 132,Other Reviews 3,bph的循证治疗,49,bph的循证治疗,50,bph的循证治疗,51,评价证据Evaluating the Validity of The Study,对每一个研究必须回

15、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 results help in caring for my patient,bph的循证治疗,52,评价方式,自己进行文献评价 Critically appraise articles yourself 借助已评价的证据

16、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 Quantification of symptomsIPSSRecommended Quantification of symptomsbother scoreRecommended Digital

17、rectal examinationRecommended Urinalysis Recommended PSA measurementRecommended Voiding diary (frequency-volume charts)Recommended Urinary flow-rate recordingOptional Postvoid residual urine volume studiesOptional Pressure-flow studiesOptional Prostate imaging (TRUS)Optional Upper-urinary-tract imag

18、ing (US or IVU)Optional Lower-urinary-tract endoscopyOptional Serum creatinine measurementNot recommended,Adapted from Fifth International Consultation 2001 on BPH. In Benign Prostatic Hyperplasia. Plymouth, United Kingdom: Health Publication, 2001:519-535,bph的循证治疗,54,BPH的治疗目标,ICBPH制定的BPH的治疗目标： 缩小前列

19、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 Medicine:Proven treatment for Clinical BPH,Evidence-based medicine is based on result

20、s 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 with drugs for clinical BPH should evaluate the effects of therapy on AUR and BPH-re

21、lated 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 Extension* MaintainedMaintainedMaintained Scandinavian Open Extension*MaintainedMaintaine

22、dMaintained,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 = Proscar Worldwide Efficacy and Safety Study; PLESS = Proscar Long-term Efficacy and S

23、afety Study *Benefits achieved during double-blind therapy were maintained in extensions,bph的循证治疗,57,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,PROSCAR,57% risk reduction p0.001,4,1,2,3,0,Probability of AUR,Years,No. of AUR

24、s36252018 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 on the Natural History of Clinical BPH: Reduced Risk of Surgery,Slide V.6,15,

25、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 Adapted from McConnell JD et al N Engl J Med 1998;338(9):557-563,Effect of PRO

26、SCAR on the Natural History of BPH: Relative Risk Reductions vs. Interventions in Other Diseases,RiskConditionOutcomeInterventionReduction (%) OsteoporosisVertebral fractureAlendronate4447Hip fracture Alendronate 2151 AtherosclerosisPTCA or CABGStatins1737 Fatal/nonfatal MI Statins 2540 EpilepsySeiz

27、uresAnticonvulsants3887 Superficial bladder cancer RecurrenceBCG + surgery3180 Kidney stonesRecurrencePharmacotherapy6380 BPHAURPROSCAR57Surgery PROSCAR 55,Slide V.7,PTCA = percutaneous transluminal coronary angioplasty; CABG = coronary artery bypass graft; BCG = bacillus Calmette-Gurin Adapted from

28、 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 preserves predictive value of PSA measurements,Slide V.8,In PLESS, PROSCAR did not ma

29、sk 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 increases in urinary flow 2.5 ml/sec increase at year 7 Consistent safety and tole

30、rability pro 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 of patients completing each trial phase Adapted from Roehrborn CG et al. Poster 419,Pla

31、cebo (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,Slide VI.4,p0.05 PROSCAR vs. placebo at every time point after 4 months to 1 year and p0.00

32、1 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;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,bph的循证治疗,65,联合治疗的理论基础,From evidences(MTOPS)and syntegration,非那雄胺,多沙唑嗪,症状改善 最大尿流率改善