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Clinical applications and Arden Syntax
Educational material, part 5
Medexter HealthcareBorschkegasse 7/5 A-1090 Vienna
www.medexter.com
www.meduniwien.ac.at/kpa (academic)
Better care, patient safety, and quality assurance by Medexter, Vienna, Austria
The ArdenSuite
EHR applications
Integration into i.s.h.medat the
Vienna General Hospital
SOP checkingin melanoma patients
receiving chemotherapy
University of Colorado Health—with Epic EHR
• patient follow-up and authorization of additional inpatient services (e.g., occupational and physical therapy)
© 2014 Epic Systems Corporation. Used with permission.
Example of e-mail from HFRRS MLM to HF nurse practitioners:
Heart failure readmission risk score
Input:
• vital signs
• lab data
• demographics
• ATD info
• ICD codes
Intensive care application
CDS integration at the cardiac ICU of the Universitätsklinikum
Erlangen
• Commercial ArdenSuite CDS engine by Medexter Healthcare connected with Dräger ICM
• Data, time, and user controlled MLM processing
from Stefan Kraus, Erlangen, Germany
from Stefan Kraus, Erlangen, Germany
cAlerts—Context-sensitive, laboratory-data-based
clinical alerts
Context-specific alerts: C-reactive protein
Rule ID Message Context Rule
CRP_slight Slightly increased CRPPrevious value in the normal range or no previous value
20 mg/l ≤ CRP < 50 mg/l
CRP_mod Moderately increased CRPPrevious value in the normal range or no previous value
50 mg/l ≤ CRP < 100 mg/l
CRP_sign Significantly increased CRPPrevious value in the normal range or no previous value
CRP ≥ 100 mg/l
CRP_cont Further increase of CRP
Patient has no leukemia and4th+ day of infection andvalue available between 12 and 36 hours prior to the current value
CRP ≥ 20 mg/l and
CRP−yesterday′s CRPyesterday′s CRP
≥ 0.20
Note: CRP, C-reactive protein concentration in mg/l
Context-specific alerts: Leukocyte count
Rule ID Message Context Rule
LpenLeukocyte value indicates leukopenia
- 0.5 G/l < leukocyte count ≤ 3 G/l
Lcyt_leukLeukocyte value indicates leukocytosis. Admission diagnosis: leukemia
Leukemia Leukocyte count ≥ 12 G/l
Lcyt_sinc Significant increase of leukocytesLeukocyte count−previous leukocyte count
previous leukocyte count≥ 0.4
Lcyt_sdecSignificant decrease of leukocytes
Leukocyte count−previous leukocyte countprevious leukocyte count
≤ −0.4
Lcyt_incIncrease of leukocytes compared to previous finding
No leukemia andno previous infection andprevious value in the normal range.
Leukocyte count ≥ 12 G/l
Lcyt_pers Persistent leukocytosis
No leukemia and4th+ day of infection andvalue available between 12 and 36 hours prior to the current value.
Leukocyte count ≥ 12 G/l and
Leukocyte count−yesterday′s leukocyte countyesterdays′s leukocyte count
≥ −0.10
Note: Leukocyte count expressed in grams (G) per liter
Inflammation monitoring and alerts
Hepaxpert—Interpretation of hepatitis serology
test results
Automated interpretation of
hepatitis serology test results
• includes frequent, rare, as well as inconsistent combinations
• complete coverage of the problem domains
• e.g., hepatitis B serology: about 150 rules in 3 layers for 61,440 possible combinations
test results
interpretation
Integration ofHepaxpert into a
laboratory information system
Hepatitis serology interpretation integrated into an EHR
Rheumexpert—Interpretive tool for
rheumatology
Differential diagnostic supportin
rheumatology
CDS Hooks and the ArdenSuite
CDS Hooks
e.g.,ArdenSuite
e.g.,Rheumexpert
Hepaxpert
adapted from: www.cds-hooks.org; light green boxes by Medexter
e.g.,databasesopenEHR
…
openEHRand the ArdenSuite
OpenEHR connector
• extension for ArdenSuite server
• RESTful connection to openEHR server
• receive openEHR data
• use data in MLM
EhrScape
• 1st MLM • 2nd MLM
Send query & return the data • calls the 1st MLM
• analyzes blood pressure for orthostatic hypotension
Screenshot from ArdenSuite IDE
Activiti BPMN and the ArdenSuite
Clinical guideline for “Hepatitis B in pregnancy: outpatient visit”
Department of Obstetrics and Gynecology, Vienna General Hospital/Medical University of Vienna, Austria
Hepatitis B breastfeeding recommendations for HBsAg positive patients
Test results Hepatitis B PCRpositive1
Hepatitis B PCRnegative2
Hepatitis B PCR unknown
HBeAg positive Don’t breastfeed or wean from breastfeeding
Breastfeeding after immunization possible
Don’t breastfeed or wean from breastfeeding
HBeAg negative Don’t breastfeed or wean from breastfeeding
Breastfeeding after immunization possible
Breastfeeding after immunization possible
HBeAg unknown Don’t breastfeed or wean from breastfeeding
Breastfeeding after immunization possible
No recommendation possible until data is available
1 Positive result corresponds to >107 genomes/ml2 Negative result corresponds to ≤107 genomes/mlNote: HBeAg, hepatitis B envelope antigen; PCR, polymerase chain reaction
Activiti BPMN workflow and MLM calls
… part of pediatrician–mother conversation
PMML and the ArdenSuite
Predictive Model Markup Language (PMML)
• XML-based file format
• representation of statistical and data mining models
• vendor-independent method to exchange models
• supported by over 20 vendors (e.g., IBM, KNIME, R)
A. Guazzelli, What is PMML?, IBM (2010). http://www.ibm.com/developerworks/library/ba-ind-
PMML1/index.html.
Data Mining Group – PMML version 4.3, from: http://dmg.org/pmml/pmml-v4-3.html
PMML to Arden Syntax transformer
• decision trees (PMML) -> Arden Syntax (MLM)
• plugin for the ArdenSuite IDE
• input: PMML file (PMML v. 4.3)
• output: MLM file (Arden Syntax v. 2.9)
some further processing with ArdenSuite IDE, e.g., add institution
Momo—Monitoring of microorganisms
Vienna General HospitalA 1,900-bed tertiary care and teaching hospital
microbiology laboratory information system
MOLIS
reports, surveillance, and analytics
MOMO58 structured parameters
pdfs structured results
• hospital information system i.s.h.med
• clinical users• laboratory & QM• hospital hygiene & infection control• hospital administration• medical research• external EHR & EMR systems
Fuzzy Arden Syntax
From: Dupré, B. The sorites paradox. In Dupré B. (2007) 50 philosophy ideas you really need to know. QuercusPublishing PLc, London, p. 122.
Lotfi
Lotfi A. Zadeh with Klaus-Peter Adlassnig, visit at Lotfi’s home in Berkeley, CA, U.S.A., on 22 Nov 2015
Welcome!
Why Fuzzy Arden Syntax? – part I
• Modeling linguistic uncertainty by fuzzy sets
‒ due to the unsharpness (fuzziness) of boundaries in linguistic concepts; gradual transition from one concept to another
‒ modeled by fuzzy sets (e.g., fever, increased glucose level, hypoxemia)
‒ a fuzzy set calculates a degree of compatibility in the range [0,1] between raw data and a linguistic clinical concept
• Modeling propositional uncertainty by fuzzy logic
‒ due to the incompleteness of medical conclusions; uncertainty in definitional, causal, statistical, and heuristic relationships
‒ modeled by fuzzy logic truth values between zero and one (e.g., 0.6, 0.9)
– to evaluate logical combinations of clinical concepts to draw conclusions about higher-level concepts; repeated use propagates results through an inference network
Why Fuzzy Arden Syntax? – part II
• Modeling two-dimensional fuzzy sets and fuzzy automata
‒ linguistic fuzzy states represent physiological or pathophysiological states
‒ state transitions are described by linguistic instructions
‒ two-dimensional fuzzy sets include time dimension
• Modeling fuzzy control
– heuristic, linguistic control rules
– here: open-loop control cycle
Fuzzy sets
• Crisp boundary
‒ Defines a sharp threshold.
‒ Checking if a given value is greater or less
than the defined crisp threshold results in
either true or false.
‒ Borderline cases are not detected.
• Fuzzified boundary
‒ Defines a gradual transition
‒ Checking if a given value is greater or less
than the defined fuzzified boundary results in a
truth value between 0 and 1
‒ Borderline cases are detected
‒ Weighted results for borderline cases, all other
are as usual
Fuzzy sets ‒ Arden vs. Fuzzy Arden
• Classical Arden Syntax
fever_limit := 38;
temperature := 37.9;
message := "patient has no fever";
IF temperature > fever_limit THEN
msg := "patient has fever";
END IF
• Result message: “patient has no fever”
• Borderline case is not detected
• Fuzzy Arden Syntax
fever_limit := FUZZY SET (37.5,0), (38,1);
temperature := 37.9;
message := "patient has no fever";
IF temperature > fever_limit THEN
msg := "patient has fever";
END IF
• Result message: “patient has fever”
(with applicability 0.8)
• Borderline case is detected
Four clinical concepts in Moni-ICU
Clinical Concept (Unit) Fuzzy Set
Normal Range Borderline Range Pathological Range
Increased body temperature (fever) (°C)
< 37.5 37.5 – 38.0 1) > 38.0 2)
Increased C-reactive protein (CRP) (mg/dl)
< 1.0 1.0 – 6.0 3) > 6.0 3)
Leukopenia (WBC/mm3) > 5,000 4,000 – 5,000 4) < 4,000 2)
Leukocytosis (WBC/mm3) < 11,000 11,000 – 12,000 4) > 12,000 2)
1) as defined by clinicians2) as defined by CDC/NHSN, ECDC, and KISS for retrospective surveillance purposes3) as defined by clinicians; CRP is an early phase protein, useful as an “infection radar” for prospective purposes4) as defined by clinicians; white blood cell count (WBC) is a slowly reacting indicator, important for surveillance
purposes
Frequency distributions: four clinical concepts as well as the topmost HAI definitions (24,325 patient days)
Clinical Concept Absent
n (%)
Borderline
n (%)
Present
n (%)
Increased body temperature (fever) 16,074 (66.1) 3,421 (14.0) 4,830 (19.9)
Increased C-reactive protein (CRP) 4,383 (18.0) 5,841 (24.0) 14,101 (58.0)
Leukopenia 22,991 (94.5) 668 (2.8) 666 (2.7)
Leukocytosis 15,169 (62.4) 1,544 (6.3) 7,612 (31.3)
BSI or1) CRI2 or UTI-A or UTI-B 20,687 (85.0) 606 (2.5) 3,032 (12.5)
1) inclusive disjunction with precedence of “present” over “borderline” over “absent”
Two different hyperglycemia definitions
hyperglycemia (surveillance) is true is 1.00.hyperglycemia (alerting) is true is 0.75.
Moni—Monitoring of hospital-acquired infections
Moni-ICU and Moni-NICU
Monitoring (for surveillance and alerts) of healthcare-associated infections (HAIs) in
ICUs with adult patients and in NICUs with neonatal patients
Characteristics
(1) PDMSs and LISs as electronic data sources provide structured medical data
(2) medical knowledge bases containing computerized knowledge of every clinical entity involved
(3) processing algorithms evaluate, aggregate, and interpret clinical data stepwise until data can be mapped into the given HAI definitions
patient-specific alerts
infection control
natural-language definitions of nosocomial
infections
Fuzzy theories
Artificial intelligence
Monitoringof
nosocomial infections
knowledge-based systems
fuzzy sets and logic
ICUICU
microbiology
cockpit surveillance remote
clinical data
Medicine
data on microorganisms
cockpit surveillance at ward
ICU
Adlassnig, K.-P., Blacky, A. & Koller, W. (2009) Artificial-Intelligence-Based Hospital-Acquired Infection Control. In Bushko, R.G. (Ed.) Strategy for the Future of Health, Studies in Health Technology and Informatics 149, IOS Press, Amsterdam, 103–110.
A bloodstream infection—with clinical signs and growth of same skin
contaminant from two separate blood samples
BSI-A2
1
clinical_signs_of_BSI (t-1d, t, t+1d)
same_skin_contaminant_from_two_separate_blood_samples
Linguistic uncertainty defined by fuzzy sets—example: fever
feverT (t-1d) ...
fever
feverT (t)
thermoregulation applied
feverT (t+1d) ...
data import
intensive care unit
maximum value
of the day
e.g., 38.5 CC
1
037 37.5 38 38.5
linguistic HAI definitions
basic concepts:symptoms, signs, test results, clinical findings
intermediate concepts:pathophysiological states
abstraction:rules, type-1 & type-2 fuzzy sets, temporal abstraction
feature extraction:mean values, scores, …
preprocessing: missing data, plausibility, …
ICU, NICU, and microbiology patient data bases
y inference stepsreasoning
symbols
data-to-symbolconversion
raw data
x inference steps
layer n (goal)
layer 0 (start)
… ……
patient-specific cockpit&
legal reporting&
quality benchmarking
Knowledge pyramid
Advanced HAI cockpit surveillance
Second study
93 ICU patient admissions; 882 patient days; 30 HAI episodes over complete or
partial duration of stay; 76 stays with no HAI episodes
De Bruin, J.S., Adlassnig, K.-P., Blacky, A., Mandl, H., Fehre, K. & Koller, W. (2013) Effectiveness of an Automated Surveillance System for Intensive Care Unit-Acquired Infections. Journal of the American Medical Informatics Association 20(2), 369–372.
Moni-ICU
goldstandard
I+ I-
I+ 26 1
I- 4 75
30 76
HAI episodes correctly / falsely identified or missed by Moni-ICU
sensitivity = 87%• 3 false-negative pneumonias + 1 false-negative CVC-related
infection due to missing microbiology
specificity = 99%• 1 false-positive CVC-related infection because of a present
concomitant leukemia (with leukocytosis)
Acceptability
Barriers to CDS
• mental
– necessity or imperative not recognized (fatalistic attitude towards risk/suffering) no innovation
– factual incomprehension (don’t understand it) no innovation
– emotional or rational refusal (don’t want it) against innovation
– insufficient endorsement (don’t do it) against innovation
• clinical
– too simplistic or insufficient quality (lack of content quality)
– lack in workflow integration (lack of process quality)
• technical
– lack in structured patient data (documentation)
– insufficient data/semantic interoperability (data and terminology standards)
• financial
– insufficient funds (often not true!)
How to overcome these barriers?
By clinically useful solutions and—last but not least—recognizing the importance
of CDS.
Combined reasons for Moni’s success
• clinical– no diagnoses, but graded compliance with definitions
– no need for additional data entry
– two-step reporting: (1) automated generation and (2) expert verification
• methodological– pure knowledge-based system with explanatory component
– consensual classification criteria
– hierarchical layers of data and knowledge
– fuzzy set theory and logic
• technical
– separation of intensive care data collection, microbiology data collection, CDS rule engine server, knowledge packages, and web-based infection control cockpit
– integration of different hospital IT systems (intensive care IT, microbiology IT, CDS IT)
• administrative– structured intensive care data and structured data from microbiology (through Momo)
– support by hospital administration
– several clinical lead users
Arden Syntax “Lego” MLMs
Faster to your destination with Arden Syntax “Lego” MLMs
clinical and microbiological building blocks
• healthcare-associated infection monitoring and surveillance
• clinical event monitoring
Clinical Arden Syntax MLM building blocks
Clinical concept Definition
Fever Body temperature > 38 °C
Leukopenia < 4,000 WBC/mm3 blood
Leukocytosis ≥ 12,000 WBC/mm3 blood
Elevated CRP CRP >10 mg/dl blood
ShockSystolic blood pressure
Heart rate<1
Drop in BPBP value in the 37.5% percentile of all averages between systolic and diastolic BP over the last 3 days
Note: WBC, white blood cell; CRP, C-reactive protein; BP, blood pressure.
Microbiological Arden Syntax MLM building blocks
Note: CFU, colony forming unit; GNB, Gram-negative bacteria.1) Specimens taken and tested in parallel; CFU ratio between catheter and peripheral sample must be > 52) Specimens taken and tested in parallel; catheter sample must test positive at least 2 hours before withdrawal of
the peripheral blood sample.
Information element Description
Positive urine culture Urine culture with ≥ 105 CFU/ml of at most two different microorganisms
Conditional positive urine culture
1. At least two urine cultures with repeated isolation of the sameuropathogen (GNB or S. saprophyticus) with ≥ 102 colonies/ml urinein non-voided specimens
2. ≤ 105 colonies/ml of a single uropathogen (GNB or S. saprophyticus)in a patient being treated with an effective antimicrobial agent for aurinary infection
Positive catheter culture 1. Quantitative culture of a catheter tip (≥ 103 CFU / ml)2. Semiquantitative culture of a catheter tip (> 15 CFU / ml)3. Quantitative positive culture of blood drawn from a central venous
catheter; with CFU/ml reported1)
4. Quantitative positive culture of blood drawn from a peripheral vein;with CFU/ml reported1)
5. Qualitative positive culture of blood drawn from a central venouscatheter2)
6. Qualitative positive culture of blood drawn from a peripheral vein2)
7. Positive culture of pus from the insertion site
The future
Begin of exponential growth
We are here.
Kurzweil, R. The singularity is near. Viking, 2005.
Licensing options—I
Licensing options—II
Licensing options—III
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