Escolar Documentos
Profissional Documentos
Cultura Documentos
Anna$Bauer)Mehren$
Shah$Lab,$Stanford$Center$for$Biomedical$Informa:cs$
Networks(
Networks$have$successfully$been$used$in$biology$and$ partly$in$medicine$
Ataxia$protein)protein$interac:on$network$(Lim$et$al,$Cell,$ 2006)$ Pa:ent$stra:ca:on$using$ICD9$data$(Roque$et$al,$PLoS(Comp( Biol,$2011)$
We$can$use$networks$from$unstructured$EHR$data$for:$
Cohort$construc:on$ Clinical$outcome$analysis$
4/2/13
Data(
STRIDE(
1.8$million$pa:ents$ 18$years$ 35$million$coded$ICD9$ diagnoses$ 11$million$clinical$free$text$ notes$
NCBO(
Clinically(relevant(hypotheses(
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From(clinical(notes(to(paBent(feature(matrix$
Ontologies$provide$features$&$dependencies$ BioPortal$$knowledge$graph$
Crea:ng$clean$lexicons$
Diseases$ Procedures$
Text$clinical$note$
Simple$text$processing,$Feature$extrac:on$
Term$$1$ :$ :$ :$ Term$$n$
Term$recogni:on$tool$ NCBO$Annotator$
Annota:on$Workow$
NegEx$ Pa[erns$
Devices$
Drugs$
Terms$Recognized$
Nega:on$detec:on$ Family$History$detec:on$
Nega:on$detec:on$
Drugs$
Diseases$
Devices$
Procedures$
C1 P1 : : Pn 1 0 0 0
0 1 0 1
1 1 0 0
Cn 1 0 1 1
C1 C1 : :
Who is getting these drugs, conditions, etc?
cephalexin cane
0.6 1
0.5 0.2 1
P1 1
0.1 1
0.7 0.5 1
Cn
ultrasound imaging
Drug$Safety$
bypass graft
doppler studies angioplasty atherectomy wheelchair cilostazol hydralazine congestive heart pneumonia failure heart failure amiodarone pravastatin carotid pantoprazole insulin glargineendarterectomy obesity zolpidem transplantation trimethoprim ramipril fentanyl diagnostic imaging revascularization vascular surgical procedures
Prac:ce)based$evidence$
Prac:ce)based$ evidence$
surgical revision
diazepam
coronary angiography
PracBceEbased(evidence(
Peripheral(artery(disease((PAD):(obstruc:on$of$infra) renal$abdominal$aorta$and$lower$extremity$arteries$$
!$Cilostazol$
4/2/13
Cilostazol(
Reversible$selec:ve$inhibitor$of$phosphodiesterase$(PDE)$type$III$ Long)term$oral$milrinone$therapy$associated$with$life)threatening$ cardiovascular$events$in$conges:ve$heart$failure$(CHF)$pa:ents$
$
$
Packer et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med. (1991)
$$$$$$
$
$
$$$$$$ $$$$$$Hypothesis:$
1.is PAD ! Cilostazol? ! MACE risk of Cilostazol not associated with increased 2. PAD/CHF ! Cilostazol? ! MACE major adverse cardiovascular events (MACE)
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Dimension(reducBon((paBent(space(
PAD
Patients (1.8 million)
Concept Peripheral artery disease Peripheral vascular disease Peripheral arterial occlusive disease Intermittent claudication Claudication (finding)
3000
PAD
50k
2000
2500
Frequency
1500
tPAD
500
1000
1000
2000
3000
4000
5000
6000
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C1 P1 : : Pn 1 0 0 0
0 1 0 1
1 1 0 0
Cn 1 0 1 1
!
Variable Treatment (n= 232) Demographics Age (at indication onset), mean (sd) Gender (female), n (%) Race , (%) Asian Black Unknown White Comorbidities Coronary artery disease, n (%) Congestive heart failure, n (%) Hypertension, n (%) Co-prescriptions Beta blocking agents, n (%) ACE inhibitors, plain, n (%) Platelet aggregation inhibitors excl. heparin, n (%) Vasodilators, n (%) History of Cardiac arrhythmia, n (%) Stroke, n (%) Myocardial infarction, n (%) Vascular surgical procedures, n (%) Bypass surgery, n (%) 71.22 (11.02) 37.22 8.52 2.69 22.87 65.47 5.38 25.56 10.76 75.34 78.03 91.93 32.29 32.29 17.94 17.94 74.44 41.70 Before Matching Control (n= 5525) 70.43 (12.46) 45.94 7.41 3.71 26.17 62.22 6.47 22.84 11.31 60.77 69.57 79.00 26.36 32.17 18.31 15.87 47.71 26.56 p-value 0.30 <0.01 0.56 0.36 0.25 0.32 0.48 0.36 0.80 <0.001 <0.01 <0.001 0.06 0.97 0.89 0.43 <0.001 <0.001 Patient-patient similarity network Control (n= 232) 72.05 (10.62) 36.65 6.33 3.61 22.17 67.87 4.98 20.36 9.50 p-value 0.41 0.84 0.37 0.59 0.82 0.55 0.83 0.21 0.75 Propensity score matching Control (n= 5525) 70.87 (11.51) 35.87 10.31 0.90 20.63 67.27 6.28 30.49 10.31 p-value 0.75 0.77 0.51 0.16 0.57 0.69 0.70 0.36 0.88
! ! ! !
Cilostazol patients are sicker than other 69.68 0.20 74.89 0.91 PAD patients 67.87 0.01 78.92 0.81
89.59 0.41 95.51 0.07
Cohort(construcBon(
PaBentEpaBent(similarity(network((PSim)(
1159( Pa:ents$
PropensityEscore(matching((PSM)(
1. Choose$variables$for$matching$
5757(
J ( A, B) = AB AB
Pa:ents$
0 0.6 0 0.8 0.8 0 0.6 0.9 0.7 0 0.5 0.8 0.9 0.7 0 0.8 0.3 0.9 0.8 0.8 0
5757(
Nearest(neighbor( Matching((1:1)(
cilostazol control
Cilostazol(
Control(
5757( Concepts$
1 0 0 1 0 0 0 1 1 0 1 1 1 0 1 0 0 1 0 0 1 0 0 1 0 1 0 1 1 1 1
Pa:ents$
17(
Pa:ents$
1159(
Pa:ents$ 464(
0 1 1 0 0
0 1 1 0 0
464(
4/2/13
10
Cohort(construcBon(
!
Variable Treatment (n= 232) Demographics Age (at indication onset), mean (sd) Gender (female), n (%) Race , (%) Asian Black Unknown White Comorbidities Coronary artery disease, n (%) Congestive heart failure, n (%) Hypertension, n (%) Co-prescriptions Beta blocking agents, n (%) ACE inhibitors, plain, n (%) Platelet aggregation inhibitors excl. heparin, n (%) Vasodilators, n (%) History of Cardiac arrhythmia, n (%) Stroke, n (%) Myocardial infarction, n (%) Vascular surgical procedures, n (%) Bypass surgery, n (%) 71.22 (11.02) 37.22 8.52 2.69 22.87 65.47 5.38 25.56 10.76 75.34 78.03 91.93 32.29 32.29 17.94 17.94 74.44 41.70 Before Matching Control (n= 5525) 70.43 (12.46) 45.94 7.41 3.71 26.17 62.22 6.47 22.84 11.31 60.77 69.57 79.00 26.36 32.17 18.31 15.87 47.71 26.56 p-value 0.30 <0.01 0.56 0.36 0.25 0.32 0.48 0.36 0.80 <0.001 <0.01 <0.001 0.06 0.97 0.89 0.43 <0.001 <0.001 Patient-patient similarity network Control (n= 232) 72.05 (10.62) 36.65 6.33 3.61 22.17 67.87 4.98 20.36 9.50 69.68 67.87 89.59 p-value 0.41 0.84 0.37 0.59 cilostazol control 0.82 0.55 0.83 0.21 0.75 0.20 0.01 0.41 Propensity score matching Control (n= 5525) 70.87 (11.51) 35.87 10.31 0.90 1 20.63 0 67.27
1 1
! ! ! !
Concepts$ 0.16
0 0 1 0 0 0 1 1 0 1 1 1 0 0.57 1 0.69 1 0 0 0 1 0 0 1 0 1 1 1 1
0.51
17(
Pa:ents$
464(
Outcome(in(PAD(paBents(
B
MACE
Myocardial infarction Stroke Death
0 1 0 1 0 1
Cn 1 1 0 0 1 1
CIL 1 1 1 0 0 0
tazol rol
similarity psm
Arrhythmias
Ventricular fibrillation Ventricular tachicardia Atrial fibrillation Cardiac arrhythmia
MALE
Bypass procedure Revascularization procedure
4/2/13
12
Dierences(in(cohorts(
4/2/13
13
A
cilostazol control
MACE
Myocardial infarction Stroke Death
similarity psm
Arrhythmias
Ventricular fibrillation Ventricular tachicardia Atrial fibrillation Cardiac arrhythmia
MALE
Bypass procedure Revascularization procedure
Natural(experiment(
No difference in MACE among patients taking Cilostazol Uncovered a natural experiment that supports what clinicians suspect
4/2/13
wheelchair
cilostazol
ultrasound imaging
amoxicillin
doppler studies angioplasty revascularization cilostazol diagnostic imaging bypass heart failure pravastatin nifedipine vascular diseases atherectomy bypass graft
pneumonia
amiodarone
fentanyl
obesity
carotid endarterectomy pantoprazole insulin glargine ramipril decompressive incision transplantation trimethoprim coronary angiography sulfamethoxazole zolpidem heart transplantation tacrolimus fluoroscopic angiography temazepam
diazepam
control
Outcome(in(CHF(paBents(
Iden:ed$and$manually$conrmed$43$PAD$pa:ents$$ with$history$of$CHF$taking$Cilostazol$despite$the$black)box$warning$
A
MACE
B
MALE
cardiac arrest amputation death (SSDI) defibrillation events myocardial infarction stroke revascularization sudden cardiac death angioplasty
bypass
0 0.5 1 1.5 2 2
Odds ratio
Conclusions$
cilostazol control
P1( P1( 1$
Pn(
Cilostazol([is(or(is(not](associated(with(increased(risk( of(major(adverse(cardiovascular(events((MACE)(
:( :( Pn(
Pa:ent)pa:ent$similarity$can$be$ used$for$cohort$building$
cephalexin
cane
C1(
doppler ultrasonography ultrasound imaging doppler studies atherectomy
Cn(
amoxicillin angioplasty revascularization cilostazol hydralazine congestive heart pneumonia failure heart failure amiodarone pravastatin carotid pantoprazole insulin glargineendarterectomy obesity zolpidem transplantation trimethoprim ramipril fentanyl diagnostic imaging vascular surgical procedures bypass graft
C1( :( :( Cn(
1$
wheelchair
surgical revision
diazepam
coronary angiography
Acknowledgements(
Shah$Lab$
Nigam$Shah$ Paea$LePendu$ Rave$Harpaz$ Srinivasan$Iyer$ Kenneth$Jung$ Amogh$Vasekar$ Sandy$Huang$ Tyler$Cole$
NCBO$Team$
Mark$Musen$ NIH$funding$
$
STRIDE$Team$
Tanya$Podchiyska$ Todd$Ferris$
Medical$collaborator$
Nicholas$Leeper$
PAMF$Team$
Cli$Olson$ $
4/2/13
17
$ We$are$hiring$postdocs!$ $ $ $ $ $nigam@stanford.edu$