EMRDatamining

NigamShahnigam@stanford.edu

1 0 -11 0 -1

1 0 -11 0 -1

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thousands

millions

hundreds

engineered

TheDataandtheproblem

ßIndividu

als(N)à

ß Features(p)à

ProceduresDevicesDiseasesDrugs Sequence,Expression(gene,protein),Metabolites…

Claims Quantifiedself

Wedoalot,withoutknowingwhatworks.

1. Clinicalquestions2. Insightsfromthedata3. Predictivemodels

Understandingthequestion

Whatproportionofthepopulationhasfamilialhyperlipidemia?

Whatarethesubtypesofautism?

Istherearelationbetweengutbacteriaanddepression?

Whichpatientswillbehigh-costnextyear?

Ismitralvalverepairorreplacementbetterforpatientswithprolapse?

HowdoesandrogendeprivationincreasedementiaRisk?

5

90773 water*on*the*brain3107785 hydrocephalus*[disease/finding]42612 hydrocephaly2889104 hydrocephalus*(disorder)1936514 hydrocephalus,*unspecified2001177 hydrocephalus*nos

2933 hydrocephalus*************************

4010253C0020255

hydrocephalus

tid cui str Note+freq syn Medline+freq %+noun2933 C0020255 hydrocephalus 29,634 NNS 19,541 64.6142612 C0020255 hydrocephaly 113 NN 275 49.8190773 C0020255 water>on>the>brain 8 ROOT 1 50

Phenotyping

Clinicalstudies

Terms,Concepts

Counts

Variables

Anyallergymed?

Profilingriskfactorsforchronicuveitis PAST MEDICAL/SURGICAL HISTORY: Positive for atrial fibrillation. The patient had AVR 6 years ago. Peripheral arterial disease with hypertension, peripheral neuropathy, atherosclerosis, hemorrhoids, proctitis, CABG, and cholecystectomy.

FAMILY HISTORY: Positive for atherosclerosis, hypertension, autoimmune diseases in the family.

REVIEW OF SYSTEMS: Weight loss of 25 pounds within the last 6 months, shortness of breath, constipation, bleeding from hemorrhoids, increased frequency of urination, muscle aches, dizziness and faintness, focal weakness and numbness in both legs, knees and feet.

LABORATORY DATA AND RADIOLOGICAL RESULTS: The patient had a chest x-ray, which showed cardiomegaly with atherosclerotic heart disease, pleural thickening and small pleural effusion, a left costophrenic angle which has not changed when compared to prior examination, COPD pattern. The patient also had a head CT, which showed atrophy with old ischemic changes. No acute intracranial findings.

DISCHARGE DIAGNOSIS: Syncope.

DISCHARGE MEDICATIONS: The patient was discharged on the following medications; Cardizem 90 mg p.o. thrice daily, digoxin 0.125 mg p.o. once daily, allopurinol 100 mg two times daily, Coumadin 4 mg p.o. q.h.s., and Remeron 15 mg p.o. q.h.s.

past medical surgical history: positive for atrial fibrillation. patient avr years ago. peripheral arterial disease hypertension, peripheral neuropathy, atherosclerosis, hemorrhoids, proctitis, cabg, and cholecystectomy.

family history: positive for atherosclerosis, hypertension, autoimmune diseases family.

review of systems: weight loss pounds months, shortness of breath, constipation, bleeding hemorrhoids, increased frequency of urination, muscle aches, dizziness and faintness, focal weakness and numbness both legs, knees and feet.

laboratory data and results: patient chest x-ray, which cardiomegaly atherosclerotic heart disease, pleural thickening and small pleural effusion, left costophrenic angle which not changed compared prior examination, copd pattern. patient head ct, which atrophy old ischemic . no acute intracranial findings.

discharge diagnosis: syncope.

discharge medications: patient following medications; cardizem mg . . daily, digoxin 0.125 mg . . once daily, allopurinol 100 mg two times daily, coumadin mg . . . . ., and remeron mg . . . . .

Input Text Annotations

True Internal Representation(with some keys shown for illustration)

53 844 58539 83 16 (colon)996 31363 13 (atrial fibrillation)1 19 (period)8 75087 12129 6158 61 316091 3 (peripheral arterial disease)254 332 124624 22 21 (comma)6198 2 (atherosclerosis)2 15 (comma)2835 22 1110647 2 (proctitis)2 92026 2 (cabg)2 411 21907 4 (cholecystectomy)1 15 (period)...

Reconstructed Representation

PAST MEDICAL/SURGICAL HISTORY: Positive for atrial fibrillation. The patient had AVR 6 years ago. Peripheral arterial disease with hypertension, peripheral neuropathy, atherosclerosis, hemorrhoids, proctitis, CABG, and cholecystectomy.

FAMILY HISTORY: Positive for atherosclerosis, hypertension, autoimmune diseases in the family.

REVIEW OF SYSTEMS: Weight loss of 25 pounds within the last 6 months, shortness of breath, constipation, bleeding from hemorrhoids, increased frequency of urination, muscle aches, dizziness and faintness, focal weakness and numbness in both legs, knees and feet.

LABORATORY DATA AND RADIOLOGICAL RESULTS: The patient had a chest x-ray, which showed cardiomegaly with atherosclerotic heart disease, pleural thickening and small pleural effusion, a left costophrenic angle which has not changed when compared to prior examination, COPD pattern. The patient also had a head CT, which showed atrophy with old ischemic changes. No acute intracranial findings.

DISCHARGE DIAGNOSIS: Syncope.

DISCHARGE MEDICATIONS: The patient was discharged on the following medications; Cardizem 90 mg p.o. thrice daily, digoxin 0.125 mg p.o. once daily, allopurinol 100 mg two times daily, Coumadin 4 mg p.o. q.h.s., and Remeron 15 mg p.o. q.h.s.

past medical surgical history: positive for atrial fibrillation. patient avr years ago. peripheral arterial disease hypertension, peripheral neuropathy, atherosclerosis, hemorrhoids, proctitis, cabg, and cholecystectomy.

family history: positive for atherosclerosis, hypertension, autoimmune diseases family.

review of systems: weight loss pounds months, shortness of breath, constipation, bleeding hemorrhoids, increased frequency of urination, muscle aches, dizziness and faintness, focal weakness and numbness both legs, knees and feet.

laboratory data and results: patient chest x-ray, which cardiomegaly atherosclerotic heart disease, pleural thickening and small pleural effusion, left costophrenic angle which not changed compared prior examination, copd pattern. patient head ct, which atrophy old ischemic . no acute intracranial findings.

discharge diagnosis: syncope.

discharge medications: patient following medications; cardizem mg . . daily, digoxin 0.125 mg . . once daily, allopurinol 100 mg two times daily, coumadin mg . . . . ., and remeron mg . . . . .

Input Text Annotations

True Internal Representation(with some keys shown for illustration)

53 844 58539 83 16 (colon)996 31363 13 (atrial fibrillation)1 19 (period)8 75087 12129 6158 61 316091 3 (peripheral arterial disease)254 332 124624 22 21 (comma)6198 2 (atherosclerosis)2 15 (comma)2835 22 1110647 2 (proctitis)2 92026 2 (cabg)2 411 21907 4 (cholecystectomy)1 15 (period)...

Reconstructed Representation

1

2

Countpresent,positivementions,aboutthepatient3

T-1 T-2 .. .. .. .. .. .. .. .. .. T-iP-1 1 0 -1P-2::::

P-n

1.8million

~3million

Deferbindingtoconcepts

Unitex

NegEx andConTextPatterns

Knowledgegraph

tf df NN JJ … VP T-1 T-2 T-3

ID Term-1 150,879 90,000 0.90 0.05 … 0.03

ID :

ID Term-nSyntactictypesFrequency Semantictypes

termmentions

Event/Outcomeconcepts

JuvenileIdiopathicArthritis

:

Uveitits

Iridocylitis

OralAntihistamines

JuvenileIdiopathicArthritisICD 9 codes696.0, 714.0, 714.2, 714.3, 714.9, 720.2, 720.9

Terms:Juvenile idiopathic arthritis, JIAJuvenile rheumatoid arthritis, JRAPsoriatic arthritisJuvenile spondyloarthropathy,spondyloarthritis,enthesitis related arthritis,sacroiliitis,reactive arthritis

Terms,Concepts

Counts

Variables

Androgendeprivation&Alzheimer’srisk

0 1 2 3 4 5 6 7

Anaphylaxis

Rhabdomyolysis

Tuberculosis

Allergic> rhinitis>

Abdominal>aortic>aneurysm>

Age

Caucasian

Ever> smoker

AntiDplatelet>medication>use

AntiDcoagulant>medication>use

AntiDhypertensive>medication>use

Statin>use

History>of>cardiovascular>disease

History>of>diabetes

History>of>malignancy

ADT>use

1.06 (1.04-1.08)

http://tinyurl.com/inf-consult

antihypertensives

Intervention

Diastolicpressure<90mmHg

Outcome

A55yearoldfemaleofVietnameseheritagewithknownasthmapresentstoherphysicianwithnewonsetmoderatehypertension

MyPatient

100

DiastolicBPwithDrugA:245DiastolicBPwithDrugB:989

1 2 3 4 5 6

90

80

70

60

MmHg

months

VariablesassociatedwithOutcome

DrugA

Asthma

Ethnicity

HDL

3 40 1 2HbA1c>10%

Example– 1:Choosingdiabetesdrugs

Scenario:WhichsecondlinedrugtousefortreatingdiabeticswhohavehighHbA1conetotwomonthsafterfirstlinetreatment?

250millionpatients

Metf->Metf (n)=377Glip->Glip (n)=30

Efficacy of monotherapy (Stanford data only)

Effectivetreatmentpathways

8.0Metforminà Glipizidevs.Pioglitazone

MetforminàSitagliptin vs.Pioglitazone

Metforminà Sitagliptin vs.Glipizide

Example– 2:Choosingchemotherapy

Scenario:For55-60yearoldwhitemalepatientwithnewlydiagnosedplasmacellleukemia(PCL),whatisthedifferenceinoverallsurvivalbetweenpatientstreatedwithintensiveversuslessintensivechemotherapy?

Example– 2:Personalizedestimate

Outlineofaninformaticsconsult

Descriptivesummary• Whathappenedaftertreatment?

Makingrecommendations• Whattreatmentchoicesaretypicallymade,givenpriormedicalhistory?Whataretypicaloutcomes?

• Estimation:WhatistheeffectoftreatmentchoiceXonoutcomeY?

XPRESS- EXtraction of PhenotypesfromclinicalRecordsusingSilver Standards

!!Time!"!

ICD-9 RX Terms Labs

3. Patient history is found after first mention of keyword

1. Build Keyword list based on terms related to “Myocardial

infarction”

Pid Notes

524

1234

765

834

…

….

…

…

…

…

…

…

….

Annotations

“Myocardial infarction” (Y/N) ?

2. Find Patients with keyword mentions +" #"

T" TP# FN#F" FP# TN#

train

test

5. Classifier is built using 5-fold cross validation

4. Feature Vectors constructed after collapsing patient timeline into normalized frequency counts for all terms, ICD-9s,

prescriptions and labs

ICD9 RX Terms Labs

4. Feature Vectors constructed after collapsing patient timeline into normalized frequency counts for all terms, ICD-9s,

prescriptions and labs

Input:config.R – withtermsearchsettingsOutput:keywords.tsv andignore.tsv

Input:getPatients.R -- config.R,keywords.tsv,ignore.tsvOutput:feature_vectors.Rda

Input:buildModel.R -- config.R,feature_vectors.RdaOutput:model.Rda

Phenotype AUC Sens. Spec. PPV

DM 0.95 91% 83 % 83%

MI 0.91 89% 91% 91%

FH 0.90 76.5% 93.6% ~20%

Celiac 0.75 40 % 90% ~4 %

Phenotyping- effortprecisiontradeoff

Acc PPV Time

0.98 0.96 1900

Acc PPV Time

0.90 0.91 2hrInsights

Learningtruerangesoflabtests DETECT:DataminingEMRsToEvaluateCoincidentTesting

Qualitymetrics

• PostsurgeryDVTrates

• UrinaryIncontinenceafterprostatecancersurgery

Time between surgery and DVT/PE event (first year after surgery)

Time in 10 day intervalsFr

eque

ncy

0 20 50 80 110 140 170 200 230 260 290 320 350

025

5075

100

PredictiveModeling

ClassificationorPrediction?

Patient’sMedicalRecord

###.##

Timeof“X”

###.#####.#####.##

Riskprediction Classification

SourceoffeaturesChoiceoffeatures

Predictingdelayedhealingwounds

59,958 patients

• Age• Gender• Insurance• Zip code

180,716 wounds• Wound type• Wound location

• Dimensions• Edema• Erythema• Rubor• Other wound qualities

Each wound assessment:68 Healogics Wound Care Centers in 26states• Center Code

Clinicallyusableperformance

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0.00

0.25

0.50

0.75

1.00

0.00 0.25 0.50 0.75 1.00Predicted probability of delayed wound healing

Obs

erve

d fra

ctio

n of

del

ayed

wou

nd h

ealin

g

PredictingCostBlooms

Panel2013-14TotalMembers:149,038

Panel2014-15TotalMembers:274,525

Learnmodel

Applymodel

PredictingCostBlooms

N=274,525Expensivein

2014=$18,028

Expensivein2015=$20,489

60%- Bloomers

40%- Persistent

Predicted,butdon’tbloom

Bloomerswemiss

CostBloommodel

WholePopulation– HighCostmodel

Correctlypredictedbloomers

0.810.430.57

AUCPPVCostCap.

0.860.510.68

Fruitfulareasofactivity

• Riskstratification:cost,latentdisease,decompensation

• Personalizingevidence:riskforme,whattreatmentwillwork

• Insightsintodiseaseprogression• Usingpassivelycollecteddata:sensors,featureengineering

• Practicemanagement:predictingmissedappointments,medicationadherence...

Openresearchproblems

• Datanonstationarity• Localvs.Globalmodels• Handlingunstructureddata(text,images,timetraces)• Outcomeascertainment(andcensoring)• Evaluation:Beyonddiscrimination• calibration,net-reclassification

• Bridgingthe“lastmile”

AcknowledgementsGroupMembers:• Scientists: SuzanneTamang,KenJung,Alison

Callahan,JuanBanda• Fellows:RainerWinnenburg,Rohit Vashisht• Engineer: VladimirPolony• BMIStudents:SarahPoole,AlejandroSchuler,

AlbeeLing,Vibhu Agarwal,DavidStark• MedStudents:GregGaskin,Jassi Pannu

Alums:AnnaBauer-Mehren (Roche),Srini Iyer(Facebook),Amogh Vasekar (Citrix),SandyHuang(Berkeley),Paea LePendu (Lexigram),RaveHarpaz(Oracle),TylerCole(BarrowInst.),SamFinlayson(Harvard),WillChen(Yale),YenLow(Netflix),ElsieGyang (FellowshipinSurgery)

Funding:• NIH – NLM,NIGMS,NHGRI,NINDS,NCI,FDA• StanfordInternal– Dept.ofMedicine,

PopulationHealthSciences,ClinicalExcellenceResearchCenter,Dean’soffice

• Fellowships – MedScholars,SiebelScholarsFoundation,StanfordGraduateFellowship

• Industry – Apixio,CollabRx,Healogics,JanssenR&D,Oracle,Baidu USA,Amgen

IT: AlexSkrenchuk,SCCIteam