資料的評讀 (II)診斷與篩檢

神經內科 王志弘

診斷的過程1.1.Initiation of diagnosis hypothesisInitiation of diagnosis hypothesis

初步診斷 我想這病人可能有 。。。

2.2.Refinement of the diagnostic causesRefinement of the diagnostic causes 修正診斷 他可能不是 X 或 Y ，但到底是何種感染呢？ Narrowing the possibilities

3.3.Defining the final diagnosisDefining the final diagnosis 最終診斷 我們應該再做個［ XX 切片］確定，再來治療

初步診斷● 目前有上萬種的診斷疾病

● 如果我們不認識這個疾病，我們就不可能考慮到這個診斷

● 關於疾病發生比例的文獻，讓我們了解各種診斷的可能性（ pretest probability ）

修正診斷● 根據

– Symptoms, 症狀– Signs, 徵象– Laboratory tests, 實驗室檢查– Imaging, 影像檢查

診斷性試驗的實證

Evidence about “diagnostic tests”

● Is this evidence about the accuracy of diagnostic test

validvalid?

● Is this (valid) evidence show that the test is useful at all?

● How can I applyapply this valid, accurate diagnostic test to a specific patient?

文獻評讀

治療性● Validity (closeness to

the truth)● Impact (size of the

effect)● Applicability

(usefulness in our clinical practice)

診斷性● Is this evidence about

the accuracy of diagnostic test valid?

● Is this (valid) evidence show that the test is useful at all?

● How can I apply this valid, accurate diagnostic test to a specific patient?

ValidValidUsefulUsefulApplyApply

什麼是『正常』

BNP vsLV dysfunction

Is this evidence about the Is this evidence about the accuracy of a diagnostic accuracy of a diagnostic

test valid?test valid?

Validity about Diagnostic Tests

●Diagnostic Test in Question

●Reference (gold) standard

常見的 GOLD STANDARDS

1. 外科或是病理標本 2. 血液培養的菌株3. 風溼熱， Jones Criteria

4. DSM IV ( 精神疾病 )

5. X 光6. 長期追蹤

代表性● 該檢查是否在適當的病患族群中被評估過（尤其是

那些在臨床上會使用此一檢查的對象）● Representative● common presentation of the target disorder● confusing presentations

● include patients, with mild and severe, early and late, treated and untreated cases.

確定性● 無 論 檢 查 結 果 如 何 ， 參 考 標 準 （ reference

standard ）是否經過確認

● 如何達到確定診斷 ?● 另一個參考標準● 長期追蹤● 確定不會延誤治療

測量● Independent and blind measurement

● Psychiatric disorders

Is this (valid) evidence show that the test is

useful at all?

Sensitivity, Specificity,

Likelihood ratios

整體盛行率Prevalence

= ( a + c) / ( a + b + c +d ) = 809 / 2579 = 31%

Pre-test probability

Positive predictive value

● 陽性預測值 = a / (a + b) = 731 / 1001 = 73%● 檢查陽性（ ferritin < 65 ）的人當中，真正有病 ~

（缺鐵性貧血）的人的比例

Negative predictive value

● 陰性預測值 = d / (c + d) = 1500 / 1578 = 95%● 檢查陰性（ ferritin > 65 ）的人當中，真正沒有

病 ~ （缺鐵性貧血）的人的比例

Positive vs Negative Predictive Value

Pre-test probability: 測前機率Post-test probability: 測後機率根據前兩張 slide ：

– Positive predictive value: 73%– Negative predictive value: 95%

假設抽血檢查前病人 ( 有病 ) 的測前機率： 50%

如果陽性反應 測後機率： 73%

如果陰性反應 測後機率： 1-95% = 5%

Sensitivity

● 敏感度 = a / (a + c) = 731 / 809 = 90%● 真正有病的人當中，檢查有問題（陽性）的比例

Specificity

● 特異度 = d / (b + d) = 1500 / 1700 = 85%● 真正沒病的人當中，檢查沒問題（陰性）的比例

Likelihood Ratio

● 可能性比率● 陽性結果的可能性比率● LR+ = ( 出現目標疾病的病人中，檢查結果為陽

性的可能性） / ( 沒有出現目標疾病的病人中，檢查結果為陽性的可能性）

● = 敏感度 / (1- 特異度 ) ● = 90% / (1-85%) = 6

Likelihood Ratio

● 陰性結果的可能性比率● LR- = ( 出現目標疾病的病人中，檢查結果為陰

性的可能性） / ( 沒有出現目標疾病的病人中，檢查結果為陰性的可能性）

● = (1- 敏感度 ) / 特異度 ● = (1-90%) / 85% = 0.12

勝算 vs 機率• Odds vs Probability

• 假設有病與沒病的機率分別是 31% ， 69%

• 則有病的勝算為： 31%/69% = 0.45

• Study pre-test odds = prevalence / (1-prevalence)

Post-test Odds測後勝算

• LR+ = ( 出現目標疾病的病人中，檢查結果為陽性的可能性） / ( 沒有出現目標疾病的病人中，檢查結果為陽性的可能性）

• LR+(ferritin)= sensitivity/(1-specificity) = 90%/15%=6

• 測後勝算 ( 陽性反應 )

• = 測前勝算 * LR+ =1 * 6 = 6

• 測後勝算 ( 陰性反應 ) = 測前勝算 * LR-

Post-test Odds vs Probability

• 測後機率 = 測後勝算 / ( 測後勝算 +1)

• Study pre-test odds = 0.45

• Study post-test odds = 0.45 *6 = 2.7

• Study post-test probability = 2.7 /(2.7+1) = 73%

Post-test Odds , Probability ( 陰性 )

• 測後機率 = 測後勝算 / ( 測後勝算 +1)

• Study pre-test odds = 0.45

• Study post-test odds = 0.45 *0.12 = 0.054

• Study post-test probability( 有病 ) = 0.054/(0.054+1) = 5%

• 測後沒病機率 = 1-5% = 95% negative predictive value

個人化調整病患測後勝算= 研究測後勝算 * ( 病患測前勝算 / 研究測前勝算 )

檢查是否有用Sensitivity 敏感度 , Specificity 特異度兩者相加減掉 100% (Youden IndexYouden Index)

至少要大於 0, 最好要大於 50%, 理想值是 100%

Rule in / Rule out

SnNout:SnNout:

– high sensitivity, negative result rule out the diagnosis

SpPin: SpPin:

– high specificity, positive result rule in the diagnosis

LR+ = sensitivity / (1-specificity)

LR- = (1-sensitivity) /specificity

D-dimer vs Deep Vein ThrombosisSensitivity: 97.7% Specificity: 46%

Ferritin vs Iron deficiency anemiaSensitivity: 90%, specificity: 85%

How can I How can I applyapply this valid, accurate this valid, accurate diagnostic test to a diagnostic test to a specific patient?specific patient?

Is the diagnostic tests

Available

Affordable

Accurate

PreciseIn our setting

Patients Pre-Test Probability

• From personal experience, prevalence statistics, practice database, primary studies

• The study patients similar to our own ?

• If the disease probability changes after the evidence

Results Affect our management?

1. Move us across a test-treatment threshold

2. Our patient willing to carry it out

3. The consequence of the test help the patient reach his/her goal

Multilevel likelihood ratios

Multiple Tests

Prediction rule

SCREENING

Screening

Early diagnosis of pre-symptomatic disease among well individual in public

Case-finding

Early diagnosis of pre-symptomatic disease among patients who came to us for other unrelated diseases

Harm of Early Diagnosis

• Label: high risk for developing some disease

• False positive screening test

• Early diagnosis may not make people live longer, but it surely makes all of them “sick” longer.

Screening 有效嗎 ?

通常願意來接受篩檢的人，對醫囑的遵從性較高 自然預後較好

早期診斷通常會找到進展較慢的疾病

Diagnostic test

診斷不是用來發現絕對的事實

是用來減少臨床診斷的不確定性