实证医学个案讨论课件

1、實證醫學個案討論急診內科何英豪醫師95-10-181實證醫學個案討論急診內科1Q: 一位76歲的男性患有輕度阿茲海默症，但未服用任何藥物。他的兒子帶他來門診就診，想要了解銀杏治療失智症的療效。2Q: 一位76歲的男性患有輕度阿茲海默症，但未服用任何藥物。PICOP: Alzheimers diseaseI: Gingko bilobaC: O: Effect3PICOP: Alzheimers disease3Search terms & StrategyKeyword: Gingko, Alzheimers diseaseDatabase: PubMedSearch strategy: Gi

2、ngko: 1414 A.D.: 50043 Gingko and A.D.:134 + English, Chinese, Human, Abstract : 67 + Clinical Trial, Meta-analysis, RCT: 154Search terms & StrategyKeywordOxford Centre for EBM Levels of Evidence (2001-5) 1a : SR (with homogeneity) of RCTs.1b: Individual RCT (with narrow confidence interval).2a: SR

3、(with homogeneity) of cohort studies2b: Individual cohort study (low quality RCT; 80% follow-up)3a: SR (with homogeneity) of case-control studies.3b: Individual case-control study. 4: Case-series (poor quality cohort and case-control studies).5: Expert opinion without explicit critical appraisal, or

4、 based on physiology, bench research or “first principles”5Oxford Centre for EBM Levels oGinkgo biloba and donepezil: a comparison in the treatment of Alzheimers dementia in a randomized placebo-controlled double-blind study Eur J Neurol 2006 Level: Ib 24-week randomized, placebo-controlled, double-

5、blind study. Aged 50-80years, mild to moderate dementiaGinkgo biloba (160 mg daily dose), donepezil (5 mg daily dose), or placebo group. No evidence of relevant differences in the efficacy of EGb 761 and donepezil in the treatment of mild to moderate Alzheimers dementia, so the use of both substance

6、s can be justified. 6Ginkgo biloba and donepezil: aA randomized, double-blind, placebo-controlled trial of two doses of Ginkgo biloba extract in dementia of the Alzheimers type. Curr Alzheimers Res. 2005 Level: Ib Randomized, placebo-controlled, double-blind, parallel-group, multicenter trial 513 ou

7、tpatients with uncomplicated dementia of the Alzheimers type scoring 10 to 24 on MMSE and less than 4 on the modified Hachinski Ischemic Score.26-week treatment with GbE at daily doses of 120 mg or 240 mg or placeboThe trial did not show efficacy of GbE, however, the lack of decline of the placebo p

8、atients may have compromised the sensitivity of the trial to detect a treatment effect. Thus, the study remains inconclusive with respect to the efficacy of GbE. 7A randomized, double-blind, plThe situation of patients with dementia may be rectified by Ginkgo biloba.Results of a health services rese

9、arch study concerning the ability of patients with dementia, quality of life of the nursing family members and total treatment costs MMV Fortschr Med 2005 Level: IIb (?) Non-randomised, two-armed cohort study with an open design 683 slightly or moderately demented patients, etween 65 and 80 years.Qu

10、ality-of-life of care-taking relatives (p 0.001) in the Ginkgo-cohort. Barthel-Index in the Ginkgo-cohort (p or = 0,001). 3.614,75 euro in the standard-cohort, 3.031,78 euro in the Ginkgo-cohort (p = 0.067). Ginkgo treatment has a valid place in caretaking structure of health services. Gingko attrib

11、utes to a higher quality of life for both care-takers and patients, the progression of disease is slowed down and treatment costs are lower.8The situation of patients withGinkgo biloba compared with cholinesterase inhibitors in the treatment of dementia: a review based on meta-analyses by the Cochra

12、ne collaboration.Dement Geriat Cogn Disord 2004 Level: Ia Cochrane Collaboration meta-analyses of ginkgo, donepezil, rivastigmine and galantamine in patients with dementia. 6 months of treatmentTrial data for cholinesterase inhibitors were more consistent than those for ginkgo, particularly regardin

13、g patient populations and outcome measures. Significant benefits on cognition vs. placebo were seen with donepezil, 5 and 10 mg, rivastigmine, 6-12 mg, and galantamine,16 and 24 mg.Significant benefit vs. placebo with ginkgo was seen only when all doses were pooled. Similar proportions of patients d

14、iscontinued treatment with ginkgo and placebo. Cholinesterase inhibitors were also well tolerated, although a significantly greater proportion of patients receiving active treatment discontinued vs. placebo with some doses. 9Ginkgo biloba compared with chGinkgo biloba extract EGb 761 in dementia: in

15、tent-to-treat analyses of a24-week, multi-center, double-blind, placebo-controlled, randomized trial.Pharmacopsychiatry 2003 Level: Ib Ginkgo biloba special extract EGb 761 (240 mg/day) in outpatients with pre-senile and senile primary degenerative dementia of the Alzheimer type (DAT) and multi-infa

16、rct dementia (MID) of mild to moderate severity. Double-blind, placebo-controlled, randomized, multi-center study The results of this ITT analysis substantiate the outcomes previously obtained with a responder analysis of the per-protocol population and confirm that EGb 761 improves cognitive functi

17、on in a clinically relevant manner in patients suffering from dementia. 10Ginkgo biloba extract EGb 761 Response patterns of EGb 761 in Alzheimers disease: influence of neuropsychological profiles.Pharmacopsychiatry 2003 Level: Ib 52-week, randomized, double-blind, placebo-controlled study with 120

18、mg EGb 761 based on cut-off points applied to Alzheimers Disease. Retrospective analysis of overall efficacy indicated that a quantitative treatment effect favorable to EGb 761 could be observed in cognitive performance (p = 0.04) and social functioning (p = 0.02). 11Response patterns of EGb 761 iAs

19、sociation of Alzheimers disease onset with ginkgo biloba and other symptomatic cognitive treatments in a population of women aged 75 years and older from the EPIDOS study.J Gerontol A Biol Sci Med Sci. 2003 Level: Ib Peripheral C4A treatment (cerebral and peripheral vasotherapeutics) and especially

20、Ginkgo biloba extracts are prescribed for memory impairment, in elderly patients. Case-control study of 1462 community-dwelling elderly women aged over 75 years. 69 women with Alzheimer-type dementia were compared with 345 paired women whose cognitive function remained normal. 7-year follow-up perio

21、d. A multivariate analysis showed that fewer women who developed Alzheimers dementia had been prescribed C4A treatment (including EGb 761) for at least 2 years (odds ratio = 0.31, 95% confidence interval = 0.12-0.82, p=.018). These results suggest that C4A treatment may reduce the risk of developing

22、 Alzheimers dementia in elderly women. 12Association of Alzheimers disInfluence of the severity of cognitive impairment on the effect of the Gnkgo biloba extract EGb 761 in Alzheimers disease.Neuropsychobiology 2002 Level: Ib 52-week, randomized, double-blind, placebo-controlled, parallel-group, mul

23、ticenter study with 120 mg of EGb, using cutoff points of 23 and 14 for MMSE score.Treatment effect favorable to EGb could be observed with respect to cognitive performance (p =0.02) and social functioning (p = 0.001) regardless of the stage of dementia, whether mild or moderately severe. Improvemen

24、t in the group of patients with very mild to mild cognitive impairment.In more severe dementia, the mean EGb effect should be considered more in terms of stabilization or slowing down of worsening, as compared to the greater deterioration observed with placebo 13Influence of the severity of cCholine

25、sterase inhibitors and Gingko extracts-are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months duration.Phytomedicine 2000 Level: Ia (?) The efficacy of four cholinesterase inhibitors (tacrine, donepezil, rivastigmine, metr

26、ifonate) and Ginkgo special extract EGb 761 in Alzheimers disease were compared. Measured on the ADAS-Cog scaleEfficacy in the delay of symptom progression or the difference in response rate between active substance and placebo, showed no major differences between the four cholinesterase inhibitors

27、and the Ginkgo special extract. Only tacrine exhibited a high dropout rate due to adverse drug reactions. Second-generation cholinesterase inhibitors (donepezil, rivastigmine, metrifonate) and Ginkgo special extract EGb 761 should be considered equally effective in the treatment of mild to moderate

28、Alzheimers dementia. 14Cholinesterase inhibitors and The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: new results of a randomized clinical trial. J Am Geriat Soc 2000 Level: Ib A 24-week,randomized, double-blind, placebo-controlled, parallel-group, multic

29、enter trial. 214 older persons with dementia (either Alzheimers dementia or vascular dementia; mild to moderate degree) or age-associated memory impairment. EGb 761(2 tablets per day, total dosage either 240 (high dose) or 160 (usual dose) mg/day) or placebo (0 mg/d). Intention-to-treat analysis sho

30、wed no effect on each of the outcome measures for participants who were assigned to ginkgo (n= 79) compared with placebo (n = 44) for the entire 24-week period. No beneficial effects of a higher dose or a prolonged duration of ginkgo treatment were found. Ginkgo is not effective as a treatment for o

31、lder people with mild to moderate dementia or age-associated memory impairment. 15The efficacy of ginkgo for eldA 26-week analysis of a double-blind, placebo-controlled trial of the ginkgobiloba extract EGb 761 in dementia.Dement Geriatr Cogn Disord 2000 Level: IIa ITT analysis: after 26 weeks treat

32、ment with a 120-mgdose (40 mg t.i.d.) of EGb 761 (EGb). Double-blind, placebo-controlled, fixed dose, parallel-group, multicenter study.Mildly to severely impaired Alzheimers disease or multi-infarct dementiaFrom 309 patients, 244 patients (76% for placeboand 73% for EGb). Placebo group showed a sta

33、tistically significant worsening in all domains of assessmentEGb was considered slightly improved on the cognitive assessment and the daily living and social behavior. Mean treatment differences favored EGb with 1.3 and 0.12 points, respectively, on the ADAS-Cog (p = 0.04) and the GERRI (p = 0.007).

34、 16A 26-week analysis of a doubleThe pharmacological effects of ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine.Psychopharmacol Bull 1998 Level: III EGb or tacrine, possible or probable Alzheimers, open, uncontrolled trial 18 subjects an average age of 67

35、.4 years with light to moderate dementia Randomly a single oral Test-Dose of either 40 mg of tacrine or240 mg of EGb2 in two separate sessions within 3- to 7-day intervals. The results also showed that 240mg of EGb has typical cognitive activator CEEG profiles (responders) in more subjects (8 of 18)

36、 than 40 mg tacrine (3 of 18 subjects). Because of the small sample size, we could not test the hypothesis that subjects who showed cognitive activator-type pharmacological response to the first Test-Dose of EGb or tacrine also exhibit more therapeutic effects (compared to nonresponders) when drugs

37、are administered chronically. 17The pharmacological effects ofClinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer type.J Psychiatr Res 1997 Level: Ib 240 mg/day of Ginkgo bilabo special extract EGb761 Double-blind, randomized, placebo-controlled in 20 outpatients,

38、 3 monthsPsychometric confirmation of efficacy (SKT test)Psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels Evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. 18

39、Clinical efficacy of Ginkgo biA placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group.JAMA 1997 Level: Ib A 52-week, randomized double-blind, placebo-controlled, parallel-group, multicenter study. Mildly to severely demented ou

40、tpatients with Alzheimer disease or multi-infarct dementiaEGb (120 mg/d) or placebo. ADAS-Cog, GERRI, and CGIC. 202/309 patients included in an intent-to-treat analysisEGb group had an ADAS-Cog score 1.4 points better than the placebo group (P=.04) and a GERRI score 0.14 points better than the placebo group (P=.004). EGb was safe and appears capable of stabilizing and in a substantial number o