Transcript Document 7562981

外科實證醫學課程
Somatostatin Analogues for Acute
Bleeding Esophageal Varices
外科
莊世昌 醫師
執行EBM的五個步驟 ( I )
1.問問題（可以回答的問題）
 Converting
the need for information into an
answerable question.
2.找資料（可獲得最好的證據資訊）
 Search
the database and tracking down the
best evidence.
3.分析判斷（文獻的效度與重要性）
 Critical
appraising that evidence for its
validity and importance.
執行EBM的五個步驟 ( II )
4.臨床應用（整合三大層面）
 Integrating
the critical appraising with our
clinical expertise and our patient’s unique
biology, values and circumstances.
5.評估成果（執行EBM的效率）
 Evaluating
our effectiveness and efficiency
in executing step 1- 4 and seeking ways to
improve them both for next time.
Case
 王xx
56 y/o male
 Hepatitis B Hx for 20+ years
 Liver cirrhosis since 3+ years
 UGI bleeding 2 episodes => Gastroendoscope: EV
bleeding
 Admission due to 3rd GI bleeding
Background Knowledge
Portal Vein
Physiology
Portal pressure (5-8mmHg)
1. Esophagogastric varices :
coronary & short gastric v. to
azygos v.
2. Caput medusae : epigastric v.
3. Retroperitoneal callateral
vessels
4. Hemorrhoid venous plexus
5. Intrahepatic shunts
Esophageal Varices
Treatment
A. Noninterventional
1. Vasopressin, terlipressin
2. Somatostatin
3. Balloon tamponade
B. Interventionsal, nonsurgical
4. Endoscopic sclerotherapy
5. Endoscopic ligation
C. Surgical
6. Emergency portasystemic shunts
7. Esophageal transection and reanastomosis
8. Esophagogastric devascularization
9. Suture ligation of varices
Medications
1.
2.
3.
4.
Vasopressin (血管加壓素)
Terlipressin
Somatostatin (體抑素)
Octreotide
Octreotide
1.
Sandostatin 0.1mg/1ml/Amp
2.
Long-acting somatostatin analog
3.
降低奇靜脈血流
半衰期: 90 min
IV bolus 50-250 ug, continuous 50-250 ug/h
Side effects: hyper or hypoglycemia, Abd. pain,
nausea, diarrhea, headache
4.
5.
6.
Objectives
 To
study whether somatostatin or analogues
improve survival or reduce the need for blood
transfusions in patients with bleeding
oesophageal varices.
How to Ask Clinical Question
You Can Answer?
問題以PICO形式呈現
Patient or
Problem
Description
of the
patient or
the target
disorder of
interest
Intervention
Comparison
Intervention
Could include: Relevant
most often
Exposure
when
looking
Diagnostic test
at therapy
Prognostic
questions
factor
Therapy
Patient
perception etc.
Outcome
Clinical
outcome of
interest to
you and
your patient
Patient /
Problem
56 Y/O male liver cirrhosis with EV
bleeding
Intervention Somatostatin Analogues
Comparison
Placebo
Intervention
Outcome
Decrease mortality , ……
Step2 :Search Data for evidence
搜 尋 技 巧 與 策 略
 資料庫的選擇
 關鍵字的設定
 學習各種資料庫的搜尋方法
 圖書館定期開課
常用實證醫學電子資源
尋找文獻證據
醫學資料庫
已經整理的文獻
網路資源
未經整理的文獻
1.Cochrane Library
2.EBMR
3.UptoDate
4.Clinical Evidence
5. ACP J. club
1.Medline
2.PubMed
Step 3
Critical appraisal
文獻的分析判斷

文獻的結果是否有可信度？ (Validity)

文獻的結果是否有重要性？ (Importance)

此資料如何運用於臨床工作?(Practice)

文獻的分析判斷前需先分類，不同種類的文獻，研究方法不
同，評判方式也有異。
最常見的四類文獻：Therapy, Harm, Diagnosis, Prognosis
Diagnostic study important
Sensitivity
 Specificity
 Likelihood ratio for a positive test result
 Likelihood ratio for a negative test result
 Positive predictive value
 Negative predictive value
 Pre-test probability (prevalence)
 Pre-test odds = prevalence/(1-prevalence)
 Post-test odds = pre-test odds  LR

Therapeutic study important
 Control
event rate (CER)
 Experimental event rate (EER)
 Relative risk reduction (RRR)
 Absolute risk reduction (ARR)
 Number needed to treat (NNT)
The Evidence Pyramid
Levels of Evidence and Grades of Recommendations
Grade of
Recommendation
Level of
Evidence
Therapy/Prevention, Aetiology/Harm
Prognosis
A
1a
SR (with homogeneity*) of RCT
SR (with homogeneity*) of inception
studies, or a CPG validated on a test set
A
1b
Individual RCT (with narrow
Confidence Interval)
Individual inception cohort study with
80% follow-up
A
1c
All or none
All or none case-series
B
2a
SR (with homogeneity*) of cohort
study
SR (with homogeneity*) of either
retrospective cohort studies or untreated
control groups in RCTs
B
2b
Individual cohort study (include low
quality RCT; e.g., <80% follow-up)
Retrospective cohort study or follow-up
untreated control patients in an RCT; or
CPG not validated in a test set.
B
2c
“Outcomes” Research
“Outcomes” Research
B
3a
SR (with homogeneity*) of casecontrol studies
B
3b
Individual Case-Control Study
C
4
Case-series (and poor quality cohort
and case-control studies)
Case-series (and poor quality prognostic
cohort studies)
D
5
Expert opinion without explicit
critical appraisal, or based on
physiology bench research or “first
principles”
Expert opinion without explicit critical
appraisal, or based on physiology bench
research or “first principles”
Seach Result
Cochrane標誌及其意義
Cochrane協作網標誌（見圖）由一個圓形圖以及圍繞圓形圖
的兩個粗體同心半環圖共同構成。
1. 每一橫線代表一個試驗結果的可信區間，橫線越短則試
驗精度越高，結果越肯定
2. 垂直線（代表OR=1）將圓一分為二，可用於判斷結果差
別有無統計學意義，以區別治療效果，一般來說具有療
效的試驗結果分佈於垂直線左側;若橫線落在垂直線右側,
則表明治療結果無效。
3. 橫線與垂直線相接觸或相交，則表明該RCT中的不同治療
措施間差異無統計學意義。
4. 圓形圖內下方的菱形符號代表7個RCT的綜合結果。符號
位於左邊表明治療措施有效，位於右邊則表明治療措施
弊大於利。
該圓形圖展示了一項短程價廉的激素類藥物
Hydrocortisone治療可能早產的孕婦療效的隨
機對照試驗系統評價結果。第一個試驗於1972
年報導。至1991年，另外6項試驗結果也相繼報
導，但7個試驗結果不一致，該療法是否利大於害，根據
單個的臨床試驗結果難以確定。而系統評價結果明確肯定：
Hydrocortisone的確可降低新生兒死於早產併發症的危險，
使早產兒死亡率下降30%-50%。直至1989年，由於沒有進
行相關的系統評價分析和報導，多數產科醫師並未認識到
該項治療措施的效果,成千上萬的早產兒可能因其母親未
接受相應治療而死亡（還耗費更多不必要的治療費用）。
在臨床醫學中,由於未能根據RCTs製作出及時的、不斷更
新的系統評價而導致以生命為代價的這類例子，不勝枚舉。
Seach Strategy
 MEDLINE
(PubMed) from 1966 to Feb 2004
 Key
word: (somatostatin or octreotide or
vapreotide or lanreotide) combined with (varic* or
bleed* or hemorrhag* or hematemesis or melena)
 The
Cochrane library
 Key
word: (somatostatin explode all trees (mesh)
or somatostatin* or octreotide or vapreotide or
lanreotide) and (varic* or bleed* or hemorrhag* or
hematemesis or melena )
Selection Criteria
 All
randomised trials comparing
somatostatin or analogues with placebo or no
treatment in patients suspected of acute or
recent bleeding from oesophageal varices.
Description of Studies
 Included
20 trials (2518 patients, average of
about 100 patients per trial)
 The dose schedules and length of treatment
were quite variable
Methodological Quality
Double-blind: nine trials
 Blinding during data analysis: four trials
 All or nearly all (90%) of the randomised patients in
the analysis: seven trials
 In four trials, some of the randomised patients were
excluded because the source of bleeding was
judged to be non-variceal
 In the remaining trials it was not clear whether there
had been additional patients that were not accounted
for.

 The
trials were divided in two groups
 High-quality
group: the allocation of patients to
treatment groups had to be concealed and the
trials had to be double-blind
 Low-quality group
Types of Outcome Measures
Mortality.
 Number of blood transfusions.
 Number with balloon tamponade.
 Number failing initial haemostasis.
 Number with rebleeding.

Results (1)
 The
drugs did not reduce mortality
signicantly
 Relative
risk 0.96 (95% condence interval (CI)
0.74 to 1.24) for the high-quality trials
 0.79 (95% CI 0.61 to 1.02) for other trials
Mortality
Results (2)
 Units
of blood transfused
 Relative
risk: 0.7 (0.3 to 1.2) less with drugs in the
high-quality trials
 1.5 (0.9 to 2.0) less in the low-quality trials.
Number of
Transfusions
Results (3)
 Number
of patients failing initial hemostasis was
reduced, relative risk 0.67 (0.53 to 0.86).
Number
Failing Initial
Hemostasis
Results (4)
 Rebleeding
 Relative
was not signicantly reduced
risk 0.82 (0.45 to 1.49) in the high-quality
trials
 Relative risk 0.35 (0.18 to 0.67) in the low-quality trials,
Number With Rebleeding
Results (5)
 Use
of balloon tamponade was rarely reported.
Number with Balloon Tamponade
Basic Calculations
Odds Ratio
OR
(a/b) / (c/d)
Relative Risk
RR
[a/(a+b)] / [c/(c+d)]
1 – RR
Relative Risk Reduction
Absolute Risk Reduction
ARR
[a/(a+b)] – [c/(c+d)]
Number Needed to Treat
NNT
1 / ARR
Q&A
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