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中國醫藥大學附設醫院

實證醫學競賽

D95652 黃碩焜
D29875 陳韋勳
D30008 黃詩涵
OUTLINE - 6A

Analysis 臨床場景分析

Ask 提出臨床問題

Acquire 搜尋最有用的資料

Appraisal 嚴格評讀文獻

Apply 應用到病人身上

Audit 自我評估

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1
ANALSIS
臨床場景分析

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CLINICAL SCENARIO

老王因為兩膝疼痛被診斷有骨關節炎
(osteoarthritis) ,進聽說葡萄糖胺 (glucasamine)
對於減少膝蓋疼痛頗有效果,並不會比非類固消
炎劑差,是真的嗎 ?
患者的考量問題

1. 在骨關節炎的患者,使用葡萄糖胺,相較於
NSAID ,對減少膝蓋疼痛的療效差異。

2. 在骨關節炎的患者,使用葡萄糖胺,相較於
NSAID 所產生的副作用差異 ?
背景資訊

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相關知識

疾病說明:
Osteoarthritis (OA) was previously thought to be a normal consequence of
aging, thereby leading to the term degenerative joint disease. However, it is
now realized that OA results from a complex interplay of multiple factors,
including joint integrity, genetics, local inflammation, mechanical forces, and
cellular and biochemical processes.

常見病因、危險因子 / 機轉:
OA is linked to one or more factors, such as aging, occupation, trauma, and
repetitive, small insults over time. These associations are strongest for OA of
the knee and hand and are less strong for the hip.
相關知識

常見治療方法 / Indication :

Drug: NSAID, opioid, Capsaicin, duloxetine, and


intraarticular Glucocorticoids
Non drug: weight management and exercise, braces and
foot orthoses for patients suitable to these interventions.

治療效果:

The main medications used in the pharmacologic


management for OA pain control is NSAID.

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2
ASK
提出臨床問題
Patient > Intervention > Comparison > Outcome

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• PICO – 1
在骨關節炎的患者,使用葡萄糖胺,相較於
NSAID ,對減少膝蓋疼痛的療效差異。

Patient Mid-year-old man with knee osteoarthritis

Intervention Glucosamine

Comparison NSAID
Clinical outcomes
Outcome (Quality of life, Pain, Progression)
■ 治療 / 預防 □診斷 □危害 / 病因 □預後
Type of Question
□其他
• PICO – 2
在骨關節炎的患者,使用葡萄糖胺,
• 相較於 NSAID 所產生的副作用差異 ?

Patient Mid-year-old man with osteoarthritis

Intervention Glucosamine

Comparison NSAID

Outcome Side effect.


□ 治療 / 預防 □診斷 ■危害 / 病因 □預後
Type of Question
□其他
搜尋文獻類型

Ref.
Users' Guides to the Medical Literature: A Manual for
Evidence-Based Clinical Practice2nd Edition. Gordon
Guyatt, Drummond Rennie, Maureen O. Meade, and 12
Deborah J. Cook. 2008, ISBN: 978-0-07-159036-5
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ACQUIRE
搜尋最有用的資料
MeSH Term Integrated with Search Strategy

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MeSH EXAMPLE

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SEARCH STRATEGY
資料庫資源:■ ACCESSSS ■Cochrane Library ■PubMed ■Dynamed

AND AND AND

P I C O
knee “Glucosamine” “NSAID” 1. Quality of life
osteoarthritis [Mesh] [Mesh] 2. Pain
3. Progression
Rate
6S MODEL

DiCenso A, Bayley L, Haynes RB. Accessing preappraised evidence: fine-tuning the 5S model into a 6S 16
model. ACP J Club 2009;151:JC3-2, JC3-3. Reproduced by EVMS Brickell Medical Sciences Library
PUBMED SEARCH

17
18
19
N = 10 N = 11 N = 27

搜尋文獻共 48 篇

不符合 PICO
排除
重複文章 N=42
品質不佳
文章較舊
其他國語言

6篇

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Pubmed
RTC+systematic review, 2015
1. Efficacy and safety of glucosamine, diacerein, and NSAIDs in osteoarthritis
knee: a systematic review and network meta-analysis. (2015)

2. Effects of glucosamine sulfate on the use of rescue non-steroidal anti-


inflammatory drugs in knee osteoarthritis: Results from the Pharmaco-
Epidemiology of GonArthroSis (PEGASus) study.(2016)

3. A clinical study on glucosamine sulfate versus combination of glucosamine non RCT, not Glucosamine vs
sulfate and NSAIDs in mild to moderate knee osteoarthritis. (2012) NSAID, research was too old

4. Nonsteroidal Anti-Inflammatory Drug or Glucosamine Reduced Pain and


Improved Muscle Strength With Resistance Training in a Randomized
Controlled Trial of Knee Osteoarthritis Patients (2011)

Cochrane

5. A clinical study on glucosamine sulfate versus combination of glucosamine


sulfate and NSAIDs in mild to moderate knee osteoarthritis (2014)

6. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and


improved muscle strength with resistance training in a randomized
controlled trial of knee osteoarthritis patients (2012)

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Impact Factor: 1.68 Ranking: 84/124

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Patient

• Background: To conduct a systematic review and


network meta-analysis of randomized controlled trials
(RCTs) with the aims of comparing relevant clinical Outcome
outcomes (that is, visual analog scores (VAS), total and
sub-Western Ontario and McMaster Universities
Osteoarthritis index (WOMAC) scores, Lequesne
algofunctional index, joint space width change, and
adverse events) between diacerein, glucosamine, and
placebo.
Intervention
• Methods: Medline and Scopus databases were
searched from inception to 29 August 2014, using
PubMed and Scopus search engines and included
RCTs or quasi-experimental designs comparing clinical
outcomes between treatments. Data were extracted
from original studies. A network meta-analysis was
performed by applying weight regression for continuous
outcomes and a mixed-effect Poisson regression for
dichotomous outcomes.
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APPRAISAL
嚴格評讀文獻

Systemic Review
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Yes Can‘t tell No
1. Did the review address a clearly
focused question? V

本篇論文
情境
與情境相同
Mid-year-old man
P with knee O
osteoarthritis
I Glucosamine O
C NSAID O
O Clinical outcomes O

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Yes Can‘t tell No
2. Did the authors look for the right
type of papers? V

Inclusion criteria Randomized controlled trials or quasi-experimental designs


comparing clinical outcomes between treatments in primary OA patients’ knee
were eligible if they met the following criteria:

● Compared clinical outcomes between glucosamine (either glucosamine


sulfate or glucosamine hydrochloride) and diacerein, or each of these
treatments with other comparators (for example, placebo, non-steroidal
anti-inflammatory drugs).
● Compared at least one of the following outcomes: pain score, function,
patient/physician global assessments, range of motion, joint space width
difference, and adverse events.
● Had sufficient data to extract and pool: reported mean, standard deviation
(SD), numbers of subjects according to treatments for continuous outcomes,
and number of patients according to treatment for dichotomous outcomes.
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Yes Can‘t tell No
3. Do you think all the important,
relevant studies were included? V

Select Databases Medline, Scopus


databases
Follow up reference lists x
Personal contact with experts x
Search for unpublished x
Search for non-English language studies x 30
Yes Can‘t tell No
4. Did the review’s authors do enough
to assess the quality of the included V
studies?

Identified studies were selected by one author (J.K.) and


randomly checked by A.T. Titles and abstracts were
initially screened; full papers were then retrieved if a
decision could not be made from the abstracts. The
reasons for ineligibility or exclusion of studies were
recorded and described.

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Yes Can‘t tell No
4. Did the review’s authors do enough
to assess the quality of the included V
studies?

Inclusion criteria Randomized controlled trials or quasi-experimental designs


comparing clinical outcomes between treatments in primary OA patients’ knee
were eligible if they met the following criteria:

● Compared clinical outcomes between glucosamine (either glucosamine


sulfate or glucosamine hydrochloride) and diacerein, or each of these
treatments with other comparators (for example, placebo, non-steroidal
anti-inflammatory drugs).
● Compared at least one of the following outcomes: pain score, function,
patient/physician global assessments, range of motion, joint space width
difference, and adverse events.
● Had sufficient data to extract and pool: reported mean, standard deviation
(SD), numbers of subjects according to treatments for continuous outcomes,
and number of patients according to treatment for dichotomous outcomes.
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Cochrane “Risk of bias”
Author Seq
uen
tool
Allocation
concealment
Blinding Incomplete
outcome
Selective
outcome
Other
source of
Description of
other bias
ce data report bias
gen
erat
ion

Pujalte JM U U Y U Y U Did not mention about ITT

Lopes VA U N N U Y U Did not mention about ITT

Muller FH U U Y Y Y Y

Noack W U U Y Y Y Y

Nguyen M U U Y Y Y N Unbalance between baseline age and disease duration

Qiu GX U U Y Y Y U Did not mention about ITT

Houpt JB Y Y Y Y Y N Unbalance between baseline WOMAC score

Rindone JP
U U Y U Y U Did not mention about ITT

Pelletier JP Y Y Y N Y Y

Reginster JY Y Y Y N N Y

Dougados M Y Y Y N Y Y

Hughes R Y Y Y Y Y U Did not mention about ITT

Pavelka K Y Y Y N Y Y

Braham R N N Y Y Y Y

Cibere J Y Y Y Y Y Y
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Yes Can‘t tell No
4. Did the review’s authors do enough
to assess the quality of the included V
studies?
> 2 Assessor O

Valid criteria O

Cochrane “Risk of bias” tool O

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Yes Can‘t tell No
5. If the results of the review have
been combined, was it reasonable to V
do so?
Direct comparisons of continuous outcomes were measured at the end of each study between
glucosamine versus placebo and diacerein versus placebo and were then pooled using an
unstandardized mean difference (UMD). Heterogeneity of the mean difference across
studies was checked using the Q statistic, and the degree was quantified using the I 2 statistic. If
heterogeneity was present (P value <0.10 or the I 2 > 25%), the UMD was estimated using a random effects
model; otherwise, a fixed-effects model was applied.

For dichotomous outcomes, a relative risk (RR) of adverse reactions of treatment comparisons
at the end of each study was estimated and pooled. Heterogeneity was assessed using the same
method as mentioned previously. If heterogeneity was present, the DerSimonian and Laird method [10]
was applied for pooling; otherwise, the fixed-effects model by inverse variance method was applied. Meta-
regression was applied to explore the source of heterogeneity (for example, mean age, percentage of
females, bone mass index (BMI), Kellgren-Lawrence grading, duration of OA) if data was available.
Publication bias was assessed using contour-enhanced funnel plots [11,12] and Egger tests [13].

For indirect comparisons, network meta-analyses were applied to assess all possible effects of
treatment measured at different times if summary data were available for pooling [14-16]. A linear
regression model weighted by inverse variance was applied to assess the treatment effects with
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adjustment for study effects and time for continuous outcomes. For adverse events, a mixed-effect Poisson
regression was applied to assess treatment effects [15].
Yes Can‘t tell No
6. What are the overall results of the
review? V

● pain VAS
● total WOMAC scores
● subWOMAC scores
Primary ● Lequesne algofunctional
Outcome index
● Joint space width
including pain, stiffness, and
function

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The mean VAS was −0.90 (95% CI: −1.67, −0.14) units
signifi- cantly lower in glucosamine than in NSAIDs
(Table 2).

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Yes Can‘t tell No
7. How precise are the results?
V

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Yes Can‘t tell No
8. Can the results be applied to the
local population? V

● 24/27 of the studies included OA of the


knee
● Mean age: 42 to 69 years
Inclusion criteria ● Body mass index: 24.0 to 32.6 kg/m²
● Duration of OA: 1.6 to 13 years
● Females: 5.1% to 88%
● Duration of treatment: 4 weeks to 3 years

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Yes Can‘t tell No
9. Were all important outcomes
considered? V

● Pain VAS
● Total WOMAC scores
Outcome ● SubWOMAC scores
● Lequesne algofunctional index
● Joint space width
Including pain, stiffness, and function

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Yes Can‘t tell No
10. Are the benefits worth the harms
and costs? V

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評讀總表
1. Did the study address a clearly focused issue?
2. Was the cohort recruited in an acceptable way?
3. Do you think all the important, relevant studies
were included?
4. Did the review’s authors do enough to assess the
quality of the included studies?
5. If the results of the review have been combined,
was it reasonable to do so?
6. What are the overall results of the review?
7. How precise are the results?
8. Can the results be applied to the local population?
9. Were all important outcomes considered?
10. Are the benefits worth the harms and costs?

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評讀偏誤
1. NSAID 的項目、頻次、使用方式?

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• 證據等級

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5
APPLY & AUDIT
應用到病人身上 & 自我評估

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1. 我們和研究中的病人是否非常不
同,而不能應用此結果?
24/27 of the studies included OA of the knee

Mean age: 42 to 69 years


Body mass index: 24.0 to 32.6 kg/m²
Duration of OA: 1.6 to 13 years
Females: 5.1% to 88%
Duration of treatment: 4 weeks to 3 years

由於病人資訊不足,因此假定病人為體重正常且超過 42 歲之中年男
子,又題目寫最近聽說,合理假設老王被診斷 OA 已超過 1.6 年,因此
符合我們資料中的範圍。

Yes / No 若老王有其他疾病會導致老王在 4 周內死亡或是在 4 周內會換人工關節


則不符合我們資料的證據,因為資料都治療至少 4 周且沒有人工關節置
換。
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2. 此治療適合我們的診療環境
• 嘛?
病人或醫療體系負擔得起嘛?
Yes / No
Yes, 市售 glucosamine 約 1000~1500 元 /1000ml
以藥品級、國外原廠維骨力來說,自費五百粒約四千五百元,食品級則單方五百粒約一
千五百元、複方六十粒約一千至一千五百元

• 這樣的治療是否有提供?
Yes, 如 OSAMINE 250MG

• 經濟考量?
與非類固醇消炎止痛藥相比,一樣都有超級大包裝,
價格相對昂貴但是副作用相對較少,較難以比較使用 NSAID 的經濟考量

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由於每個人對疼痛
的感受不同,使用
止痛藥 / 葡萄糖胺的
習慣也不同,因此
較難以比較價格

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3. 我們的病人使用 Glucosamine 替
代 NSAID 治療骨關節炎可能從治療
中得到什麼好處或壞處?
好處 壞處
● Glucosamine 有較少的副 ● 使用 glucosamine 顯著較
作用 NSAID 更好之處未明
● Glucosamine 對疼痛的改
善較 NSAID 顯著

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4. 對於我們要預防的結果及我們所提供
的治療,病人的價值觀和期望值為何?

Contexual Features
Quality of Life
社會環境因素

Using Glucosamine 即使在 function 等因素上


glucosamine 療效並未大於
NSAID ,但社會多把葡萄糖
胺當作逢年過節禮品以及孝心
的表現。也未嘗不可。

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用病人能理解的語言提供建議
王先生您好,目前有臨床證據支持硫酸鹽葡萄糖胺可以改善退化性
關節炎所產生的疼痛。但是並沒有研究告訴我們市面上時常提及的
「潤滑關節,保護骨頭」的效果。另外,維骨力和非類固醇消炎藥在
疼痛緩解上也沒有顯著的差別,目前對他們的長期作用並沒有進一步
了解。不過葡萄糖胺也沒有什麼特別需要擔心的副作用,所以如果已
經買了的話就先吃吧。只是市售葡萄糖胺相關產品有可能含有許多不
明添加物,在購買的時候請小心。

由於健保已經取消維骨力的給
付,在價錢上會比非類固醇消炎藥稍
貴一點。但考量到非類固醇消炎藥可
能造成的腸胃道不適,建議還是使用
葡萄糖胺更適合。

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THANKS FOR YOUR ATTENTION

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