期刊分享

Ref: Li, R.C., Asch, S.M. & Shah, N.H. Developing a delivery science for artificial intelligence in healthcare. npj Digit. Med. 3, 107 (2020). https://doi.org/10.1038/s41746-020-00318-y

此篇文章探討醫療人工智慧應該發展的方向。過去醫療人工智慧常常是建立機器學習模型去預測單一疾病或死亡率等等。然而，醫療本身是複雜的，僅僅是預測疾病發生或是單純分類還遠遠不夠。必須要有效整合到醫療系統中並且實行(delievery AI)來改善醫療。

主要觀點包括：

1. Complex Adaptive Systems 複雜適應系統：醫療運作於複雜的系統中，AI必須設計得能適應這種複雜性。這不僅僅是部署一個ML模型的問題，而是設計一個整合了人員、流程和技術的綜合系統。

2. Multidisciplinary Approach 跨科部合作：成功地在醫療中實施AI需要跨科部合作，這中間會需要如設計思考(Design thinking)、實作、流程改善等等。

3. Evaluation and Implementation 評估與實施：AI解決方案不僅應該評估其是否能改善臨床結果，還應該評估其在現有醫療系統中的實施效果。文章建議使用像RE-AIM和SEIPS這樣的框架來評估這些維度。文章也舉例，如藥物臨床試驗在上市前經過嚴謹的流程確定有效性及安全性，甚至在做臨床試驗前都事先評估試驗如何進行能促進後續上市流程，醫療人工智慧研究也應該有類似的程序。

4. Ongoing Quality Control 持續的品質控制：文章強調需要對AI模型進行持續的監控和重新校準，以確保它們隨著後續仍然有效、穩定、及保持準確性。

心得：可以看到醫療人工智慧研究的演進已從單一模型分類疾病、預測疾病，轉變成如何實際運用改善醫療現況，這中間仍有相當大的改善空間，然而這也給了我們繼續研究的方向，也能真正改善人們的健康。

本篇文章部分修改自ChatGPT

Atrial Fibrillation 心房顫動抗凝血藥物使用

Thromboembolism Prevention 判斷是否需使用抗血栓藥物原則 (ACC/AHA/HRS guidelines 2019 focus update/2014)

* AF(Atrial fibrillation) 與 Atrial flutter 原則上當作相同方式處理

Class I 建議 (2014 guideline)

1. 當AF or atrial flutter 持續超過 48-hour 或者不知持續時間時，不管CHA2DS2-VASc score多高，Warfarin(控制在INR 2.0 ~ 3.0) 建議在轉回正常心律前(不管藥物或電擊)，建議至少需使用3週，且之後持續使用4週。(2019 guideline, NOACs並不比Warfarin差)

2. 當AF or atrial flutter 持續超過 48-hour 或者不知持續時間時需立即做Cardioversion時，抗凝血藥物需盡早使用，且持續至少4週。

3.當AF or atrial flutter 少於48-hour且有中風高風險時，intravenous heparin or LMWH或者factor Xa or direct thrombin inhibitor，建議盡早使用，且應長期使用。

4. 在轉回竇性心律後，長期使用抗凝血藥物的使用，應根據血栓形成的風險做評估‧

Class IIa 建議 (2014 guideline)

1. 當AF or atrial flutter 持續超過 48-hour 或者不知持續時間，且之前3週沒有接受抗凝血藥物治療，在Cardioversion前做TEE是合理的，確定LA(包含LAA)沒有血栓，且應在TEE之前使用抗血栓藥物及在轉回竇性心律後使用至少4週。

2. 當AF or atrial flutter 持續超過 48-hour 或者不知持續時間時， 抗凝血藥物dabigatran, rivaroxaban, or apixaban在轉回正常心律前(不管藥物或電擊)使用3週，且之後持續使用4週是合理的(reasonable)。

Class IIb 建議(2014 guideline)

1. 當AF or atrial flutter 少於48-hour且血栓形成低風險時, 使不使用抗凝血藥物都是合理的(reasonable)。

2019 Focused update: 

1. CHADVASc score: men 2, women 3 建議使用口服抗凝血藥物。

2. NOACs比起Warfarin並不更差，且在某些trial勝過Warfarin。

3. INR穩定前，應至少每週評估，穩定後至少每月評估。

4. 不論是Paroxysmal, persistent, permanent pattern的心房顫動，都應根據血栓形成風險使用抗凝血藥物。

完整文章請參考2019/2014 AHA/ACC/HRS guideline

Ref:

1. https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000000665

2. https://www.ahajournals.org/doi/10.1161/cir.0000000000000041

值班常用藥物 Medication

DKA (Diabeteic ketoacidosis)

Insulin (100 U regular insulin in 100 mL NS) run at 0.1 U/kg/h, keep glucose > 250 mg/dl 

If K<3.5, may postpone insulin until K>3.5 mEq/L

Ref:

Rosen & Barkin’s 5-Minute Emergency Medicine Consult 5TH EDITION

Atrial fibrillation

Rhythm control:  

- Amiodarone: 

 - 5–7 mg/kg over 30–60 min, then 1.2–1.8 g/d continuous infusion or in divided PO doses until 10 g total   - 600–800 mg/d divided dose until 10 g total, then 200–400 mg/d maintenance 

Rate control:

Antithrombotic therapy( If duration>48hrs, or not sure)

- Heparin: Load 80 U/kg IV; infusion at 18 U/kg/h. 

- Low-molecular-weight heparin: 1 mg/kg SC BID 

- Warfarin sodium: 2.5–5 mg/d PO, (based on INR)

- Aspirin: 50–325 mg/d 

- DOAC(dabigatran, rivaroxaban, apixaban, and edoxaban)

Ref:

1. Rosen & Barkin’s 5-Minute Emergency Medicine Consult 5TH EDITION

2. 2019 AHA/ACC/HRS Focused Update of the 2014 Guideline for Management of Patients with Atrial Fibrillation

插管用藥整理 Intubation medication

插管用藥
Midazolam (Dormicum)	Onset: 60-90 sec Duration: 1~4 hours Dose: 0.1-0.3mg/kg IV	Pros:   Cons: hypotension
Ketamine	Onset: 30 sec Duration: 5~15min Dose: 1-2 mg/kg IV	Pros: For shock, pain control, brochodilation Cons: ICP↑、CO↓
Etomidate	Onset:15-45 sec Duration:3~12min Dose: 0.3mg/kg IV	Pros: For shock, ICP↓ Cons: Adrenal suppression
Propofol	Onset: 15-45 sec Duration: 5~10min Dose: 1-2mg/kg IV	Pros: ICP↓, Seizure control, bronchodilation Cons: hypotension, propofol infusion syndrome
Thiopental	Onset: 30 sec Duration: 5~10min Dose: 3-5mg/kg IV	Pros: ICP↓, Seizure control Cons: hypotension, bronchospasm

急性代償性心臟衰竭處理 Acute Decompensated Heart Failure Management

臨床評估 Clinical evaluation

初始治療 Initial therapy

#監測生命徵象、心律
Monitor oxygen saturation, vital signs, and cardiac rhythm.

#給氧氣、建立靜脈通路、維持病人挺直坐姿
Provide supplemental oxygen if hypoxic (SpO2 <90%), place 2 IV catheters, and position patient upright.

Provide NIV as needed, unless immediate intubation is required or NIV is otherwise contraindicated; have airway management equipment readily available;

#利尿劑需盡快給予不能拖延，在鬱血性心臟衰竭及體液過多的病人
Initiate diuretic therapy without delay to relieve congestion/fluid overload:

*起手式
1.過去沒使用過利尿劑的病人可以Furosemide 40mg IV(2支)、bumetanide 1mg IV(半支)
2.長期慢性使用利尿劑或腎臟衰竭的病人可能需要用到平常的2倍劑量

#尋找造成急性代償心臟衰竭 (ADEF)的原因並給予相應性的治療，包含 Acute coronary syndrome, Hypertension, Arrhythmia, Acute aortic or mitral regurgitation, Aortic dissection, Sepsis, Renal failure, Anemia, or Drugs

 #心律過快及心房顫動的狀況考慮使用毛地黃digoxin控制心律
Patients with ADHF and AF with rapid ventricular rate often require medication (eg, digoxin) to slow their heart rate.

#若心房顫動合併血液動力學不穩需考慮使用電擊整流
Direct current cardioversion is indicated for patients with new onset AF and hemodynamic instability or refractory symptoms despite rate control.

#在急性主動脈瓣或二尖瓣迴流或升主動脈剝離病人需照會心臟外科處理
Obtain immediate cardiac surgery consultation for acute aortic or mitral regurgitation or ascending aortic dissection.

#End-organ perfusion充足狀況下考慮使用Vasodilator治療
For patients with adequate end-organ perfusion (eg, normal or elevated blood pressure) and signs of ADHF with fluid overload:

*嚴重高血壓、急性主動脈瓣或二尖瓣迴流(Undercircumstances of Severe HTN, MR, AR)考慮使用Nitoprusside
Nitroprusside: 5 to 10 mcg/min and titrate up every 5 minutes as tolerated to a dose range of 5 to 400 mcg/min

*利尿劑使用下仍不足的狀況下考慮使用IV NTG(Undercircumstances of inappropriate diuretics therapy response)
Nitroglycerin(NTG): 5 to 10 mcg/min and titrate every 3 to 5 minutes, range: 10 to 200 mcg/min.

#收縮性心臟衰竭併發ADEF停止beta-blocker使用，嚴重的ADHF或心因性休克，使用IV inotrope，例如 dobutamine或 milrinone (Primacor)，或考慮使用 IABP (Intraaortic balloon counter pulsation)

#LVOT狀況下考慮使用 beta blocker，若有肺水腫考慮使用針劑型利尿劑 ，給予IV vasopressor (eg, phenylephrine or norepinephrine); 禁止給予強心劑或血管舒張劑

#不知心臟狀況之下若有嚴重ADEF且合併心因性休克，給予IV強心劑(eg, dobutamine or milrinone), 給予或不給予IV血管收縮劑(eg, norepinephrine)，並且考慮 Mechanical support如IABP (Intraaortic balloon counter pulsation)

*各種心因性休克病因下之血管收縮作用劑使用選擇 (Circulation, 2017)

Cause or Presentation of CS	Vasoactive Management Considerations
Classic wet and cold	Norepinephrine or dopamine Inotropic agent
Euvolemic cold and dry	Norepinephrine or dopamine Inotropic agent Small fluid boluses
Vasodilatory warm and wet or mixed cardiogenic and vasodilatory	Norepinephrine Consider hemodynamics-guided therapy
RV shock	Fluid boluses Norepinephrine, dopamine, or vasopressin Inotropic agents, Inhaled pulmonary vasodilators
Normotensive shock	Inotropic agent or vasopressor
Aortic stenosis	Phenylephrine or vasopressin In patients with reduced LVEF, echocardiography- or PAC-guided dobutamine titration
Aortic regurgitation	Dopamine Temporary pacing
Mitral stenosis	Phenylephrine or vasopressin Esmolol or amiodarone
Mitral regurgitation	Norepinephrine or dopamine Inotropic agents Temporary MCS, including IABP
Postinfarction ventricular septal defect	See classic wet and cold considerations Temporary MCS, including IABP
Dynamic LVOT obstruction	Fluid boluses, Phenylephrine or vasopressin, Avoid inotropic agents, Avoid vasodilating agents, Esmolol or amiodarone RV pacing
Bradycardia	Chronotropic agents or Temporary pacing
Pericardial tamponade	Fluid bolus Norepinephrine

Ref:
1.Treatment of acute decompensated heart failure: Components of therapy
https://www.uptodate.com/contents/treatment-of-acute-decompensated-heart-failure-components-of-therapy
2.Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association, Circulation. 2017;136:e232–e268. DOI: 10.1161/CIR.0000000000000525

Oncology 腫六點

腫瘤科病房一定會被問的腫六點，可以快速的掌握一個癌症病人從最初的表現到診斷、期別、疾病，治療計畫、治療的效果及副作用、以及現在正在產生的問題，從這六點來整理一個癌症病人的發病經過。

Initial presentation
Definite diagnosis
Stage and disease extent
Treatment plan
Effect and side effect
Ongoing problem

敗血症/敗血性休克處理策略 Sepsis/Septic shock Management Strategy

Definition 定義
首先先來看看內科聖經Harrison裡對bacteremia, sepsis, septic shock的定義
Bacteremia 菌血症
Presence of bacteria in blood, as evidenced by positive blood cultures
Signs of possibly harmful systemic response
Two or more of the following conditions: (1) fever (oral temperature >38°C [>100.4°F]) or hypothermia (<36°C [<96.8°F]); (2) tachypnea (>24 breaths/min); (3) tachycardia (heart rate >90 beats/min); (4) leukocytosis (>12,000/μL), leukopenia (<4000/μL), or >10% bands
Sepsis (or severe sepsis) 敗血症
The harmful host response to infection; systemic response to proven or suspected infection plus some degree of organ hypofunction, i.e.:
1. Cardiovascular: SBP ≤90 mmHg or MAP ≤70 mmHg that responds to administration of IV fluid
2. Renal: U/O <0.5 mL/kg per hour for 1 h despite adequate fluid resuscitation
3. Respiratory: Pao2/FiO2 ≤250 or, if the lung is the only dysfunctional organ, ≤200
4. Hematologic: Platelet count <80,000/μL or 50% decrease in platelet count from highest value recorded over previous 3 days
5. Unexplained metabolic acidosis: A pH ≤7.30 or a base deficit ≥5.0 mEq/L and a plasma lactate level >1.5 times upper limit of normal for reporting lab
Septic shock 敗血性休克
Sepsis with hypotension (SBP <90 mmHg, or 40 mmHg less than patient’s normal blood pressure) for at least 1 h despite adequate fluid resuscitation or need for vasopressors to maintain SBP ≥90 mmHg or MAP ≥70 mmHg
Refractory septic shock 頑固性敗血性休克
Septic shock that lasts for >1 h and does not respond to fluid or pressor administration

敗血症(Sepsis)是人類宿主對抗病原菌(細菌、黴菌、病毒)產生的一連串全身性發炎反應，包含細胞介質的釋放 、驅使中性球細胞到達感染部位、微血管通透性的增加(使血流可到達感染部位)等等，然而人體過度的發炎反應可能反而造成更嚴重的後果。

敗血症(Severe sepsis已不再獨立出來一個名詞)及嚴重敗血性休克的處理，需要及早的處理。

Treatment 治療與處置

抗生素的使用


Reference: 1. Harrison's Principles of Internal Medicine, 19 edition

Fungal infection 黴菌感染相關議題

黴菌感染在臨床上是一個頗為棘手的問題，特別是發生在免疫不全的病人身上，需要特別的留意，除了在抗生素上的使用需注意抗菌譜外，也須根據臨床上的證據評估感染的可能性，給出合適的治療，避免走向嚴重併發症如敗血性休克及死亡。

黴菌分類 Fungus classification
Yeast - Candida spp., Cryptococcus spp., Trichosporon, Rhodotorula
Dimorphic - Blastomycosis, Paracoccidiomycosis, Coccidioidomycosis, Histoplasmosis, Sporotrichosis, Talaromyces
Mold - Aspergillus spp., Mucorymycosis, Fusariosis


抗黴菌圖譜 Anti-fungal agents spectrum

Reference:
1. Dodds Ashley, Elizabeth & Lewis, Russell & Lewis, James & Martin, Craig & Andes, David. (2006). Pharmacology of Systemic Antifungal Agents. Clinical Infectious Diseases - CLIN INFECT DIS. 43. 10.1086/504492.

黴菌感染臨床上判斷是否為疾病的三種可能性判斷，根據宿主因素、微生物學證據、病理切片、黴菌培養證據可分為Probable, Possible, Proven三種，再根據可能性投予抗黴菌用藥
Possible
1 host + 1 clinical but no mycobiological support
Probable
1 host + 1 microbiology + 1 clinical
Positive galactomannan or beta-D-glucan
Positive sputum or BAL culture
Prove
Histopathology + Culture

Chest X ray sign 常見胸部X光徵象

Kerley lines: cardiogenic pulmonary edema

A line: linear opacities extending from the periphery to the hila; they are caused by distention of anastomotic channels between peripheral and central lymphatics
B line:  short horizontal lines situated perpendicularly to the pleural surface at the lung base; they represent edema of the interlobular septa
C line: reticular opacities at the lung base, representing Kerley's B lines en face.

Reference:
1. Kerley's A, B, and C Lines, IMAGES IN CLINICAL MEDICINE, NEJM, 2009, https://www.nejm.org/doi/full/10.1056/NEJMicm0708489

休克分類 Shock classification

分布性休克 Distributive
Septic
Non-septic
Neurogenic shock
Anaphylactic shock

心因性休克 Cardiogenic
Myocardial infarction
Acute valvular damage
Arrhythmia

低血容性休克 Hypovolemic
Hemorrhagic
Non-hemorrhagic(Burns, GI losses)

阻塞性休克Obstructive
Massive pulmonary embolism
Tension pneumothorax
Cardiac tamponade

混合性休克 Mixed/unknown
Endocrine (eg, adrenal insufficiency, thyrotoxicosis, myxedema coma)
Metabolic (eg, acidosis, hypothermia)
Other – Polytrauma with more than one shock category, acute shock etiology with pre-existing cardiac disease, late under-resuscitated shock, miscellaneous poisonings

Ref:
1. Differential Diagnosis, third edition, Churchill's Pocketbooks
2. Shock(Circulatory) Ｗikipedia, https://en.wikipedia.org/wiki/Shock_(circulatory)

常見心電圖 ECG Criteria

RBBB
QRS duration > 120 ms
rsR’ “bunny ear” pattern in the anterior precordial leads (leads V1-V3)
Slurred S waves in leads I, aVL and frequently V5 and V6

Mariot Practical Electrocardiography
Lead V1 Late intrinsicoid (R' peak or lateR peak), M-shaped QRS (RSR'); sometimes wideR or qR
Lead V6 Early intrinsicoid (R peak), wide S wave
Lead I Wide S wave

LBBB
QRS duration > 120 ms
Absence of Q wave in leads I, V5 and V6
Monomorphic R wave in I, V5 and V6
ST and T wave displacement opposite to the major deflection of the QRS complex

Ref:
1. Helio, Learn the Heart, https://www.healio.com/cardiology/learn-the-heart/ecg-review/ecg-topic-reviews-and-criteria/right-bundle-branch-block-review
2. https://www.healio.com/cardiology/learn-the-heart/ecg-review/ecg-topic-reviews-and-criteria/left-bundle-branch-block-lbbb-review

3. Marriott's Practical Electrocardiography, 12e 

急性冠心症候群 Acute Coronary Syndrome 心電圖診斷

心電圖診斷 ECG Diagnosis

STEMI ST段上升心肌梗塞

1. 以J point為基準，產生新的連續兩個lead ST波段 ≥0.1 mV(1小格), 例外在V2, V3這兩個lead, 40歲以上男性 ≥0.2 mV(2小格)，40歲以下男性 ≥0.25 mV(2.5小格), 女性不限年齡≥0.15 mV(1.5小格)。

2. 新的LBBB

NSTEMI 非ST段上升心肌梗塞

產生新的連續兩個水平的(horizontal)或下斜的(Down-sloping)lead ST depression ≥ 0.05mV(半小格)，並且或者連續兩個lead T波下降超過1mm(1小格)，合併有一個prominent R wave或R/S ration>1。

梗塞位置 Location

V1-V2 – Anteroseptal
V3-V4 – Anteroapical
V5-V6 – Anterolateral
I, aVL – Lateral
II, III, aVF – Inferior

右冠狀動脈阻塞 RCA occlusion
1. ST depression in lead I
2. ST elevation lead III>II
   Proximal: ST elevation 1mm with positive T wave
   Distal: ST isoelectric with positive T wave in V4R

左冠狀動脈迴旋枝阻塞 LCX occlusion
1. ST elevation in lead II>III
2. ST isoelectric or elevated in lead I
3. ST isoelectric or depressed with negative T wave in T4R

Extension to posterior wall
=> ST depression in precordial lead
Extension to lateral wall
=> ST elevation in lead I, aVL, V5, V6

Ref:

1. Fourth Universal Definition of Myocardial Infarction, 2018 ESC/ACCF/AHA/WHF Expert Consensus Document
2. ECG in emergency Decision Making 2006 2nd Edition

# STEMI and potiential Equivalents 看到這些也要當成可能是STEMI發生

Ref: Electrocardiographic Diagnosis of Life-Threatening STEMI Equivalents: When Every Minute Counts∗ https://www.jacc.org/doi/10.1016/j.jaccas.2019.10.030

理學檢查-心音 Physical Examination-Heart sound

S1：高頻音，注意強度及是否有分裂(Splitting)，在左胸骨側可能會聽到正常的分裂S1心音，S1的大小與心室收縮力有關，在1st degree AV block時也會下降。在RBBB時可在Tricuspid area聽到分裂的S1。

S2：高頻音
Split S2
Physiologic：正常情況下主動脈瓣(A1)比肺動脈(P2)提前關閉，S2在吸氣時因Venous return增加，Pulmonary valve會更晚關閉，S2分裂心音會更明顯，可在Pulmonary area聽到。
Narrow or Single S2：如果吸氣時聽不到Split S2，如肺高壓時(Pulmonary Hypertension)因肺阻力大肺動脈瓣早期收縮 (Early pulmonic valve closure)，或Mild to moderate Aortic Stenosis (Delayed aortic valve closure)。或有一瓣膜消失或大片心室中膈缺損 (VSD)。
Wide S2 split：RBBB
Wide & Fixed S2 split：ASD/RV failure
Paradoxical (Reverse) S2 split：Severe Aortic Stenosis

S3：低頻音，為心房早期收縮射血入心室時產生turbulance之聲音。小於40歲且為運動員或體重瘦的人可能會聽到生理性的S3，大於40歲若聽到則有hemodynamic相關問題，如心室衰竭ventricular failure、左心室擴大等等。

S4：低頻音，為心房晚期收縮射血時，心室舒張異常(LV compliance)造成之聲音，如

心雜音Murmurs： 與S1, S2心音不同，時間上較長。
Loudness (Levine grade)
Gr 1: initially unaware
Gr 2: initially aware
Gr 3: Markable; no thrills
Gr 4: Complte; thrills
Gr 5: edge; thrills
Gr 6: no touch; thrills

Thrill震顫: 觸覺可以感覺得到胸壁震動


Systolic murmurs：S1與S2之間，常見為瓣膜性心臟病或正常生理現象
AS: Midsystolic, at Right base, Erb's point, Apex
HCMP: LLSB, Erb's point
PS/ASD: Left base
MR: Holosystolic, Apex
TR: Holosystolic, LLSB
VSD: Holosystolic, LLSB
Diastolic murmurs：S2與S1之間，常見為瓣膜性心臟病
AR: Early diastolic, at Right base, Erb's point, Apex
MS: Apex

Notes筆記：高頻音用聽診器diaphragm面聽，低頻音用bell面聽，輕放即可。


Ref:
1. Bates' Guide to Physical Examination and History-Taking, 11th edition
2. NTUH teaching