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AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Revolutionizing Precision Medicine w/Big Data
The Individual Exposure Health Risk Profile (IEHRP)
INFORMS Healthcare 2019
Richard Hartman, PhD
Mark Oxley, PhD
Professor of Mathematics
Department of Mathematics and Statistics
Graduate School of Engineering and Management
Air Force Institute of Technology (AFIT)
Wright-Patterson AFB, OH
29 Jul 2019
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Disclosures
• Presenter has no interest to disclose.
• No discussion of off-label uses
• The views expressed are those of the author and do not necessarily
reflect the official policy or position of the Air Force, the Department of
Defense, or the U.S. Government.
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Imagine If…
Doctors could understand the effects of
exposures on a patients health throughout
their life
Identify diseases at the molecular
level before the onset of disease
Enable rapid interventions and
supportive medical care
Reduce disability by truly preventing
disease
Demonstrate significant cost savings and
efficiencies
3
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Total Exposure Health
TEH Overview
TEH aims to capture workplace, environmental & lifestyle exposures to the individual (i.e., N=1, genome) using advances in science,
technology & informatics to prevent disease; improve health and well-being: Healthiest Performing Population by 2025
E
H
Increase use of genomic
research and knowledge
Improve exposure monitoring
through sensors and wearables
Better understanding of monitored
exposure to performance and
individual health outcomes
Advance operational decisions
using advancements in science,
medicine, technology, and
informatics with digital biodata
bank, Big Data analytics, and
expert systems
Total Exposure Health (TEH) represents a paradigm shift in military medicine – from a primary focus on disease and injury treatment to a more
holistic approach that focuses on health and prevention.
4
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Reimagining Healthcare with TEH
TEH will bring together distinct systems and initiatives into one portfolio: integrating exposure science, information technology, and existing healthcare
programs to develop end-to-end systems.
TEH capabilities will maximize the value of these advances by translating data collection, analysis, management, and visualization into clinically and
personally actionable results.
5
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
INDIVIDUAL EXPOSURE HEALTH RISK
INDEX/PROFILE (IEHRI/P)
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Our Clinical Disposition
Individual Exposure Health Risk Index/Profile (IEHRI/P)
Our Unique Genetic Proclivity
IEHRI/P:
Individual Exposure
Indices/Profile
Our Exposures
7
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
IEHRI/P: Expressed Mathematically
IEHRI
IEHRP
8
Individual Exposure Health Risk Profile (IEHRP) = (IEHRI 1, IEHRI 2 ,…, IEHRI i ) = ([v1,1
+ v1,2 + v1,3 ], [v2,1 + v2,2 + v2,3] ,…, [vi,1 + vi,2 + vi,3])
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Visualizing the IEHRP – Individual
IEHRP will aid in visualizing an
individual’s unique exposure
susceptibilities
Lee
NOISE BENZENELEAD RADIATION GLUTEN
SUSCEPTABILITY
HIGH
LOW
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
IEHRI with Multiple Variables
• Limitations to the IEHRI became evident,
which only accounted for three variables
to describe an individual exposure.
• This required the IEHRP to be modified
so it could account for multiple
confounding factors
IEHRP = (IEHRI1 , IEHRI2 , … , IEHRIj )
= ([v1,1 + v1,2 + v1,3 +…+ v1,j ] , [v2,1 + v2,2 +
v2,3 +…+ v2,j ] , … , [vi,1 + vi,2 + vi,3 +…+ vi,j ])
Genetics
Diagnostics
Sensors and
Mobile Data
Lifestyle
Occupation
Medical History
Environment
Family History
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
IEHRI & IEHRP: Expanded
IEHRP
 IEHRI – Which vi,j value is more important?
 WFi,j = weighting factor– importance of each variable (vi,j) when compared with all the variables
with in the IEHRI (e.g., are genes more important than exposure measure?)
 CFi,j = correction factor – variability (confidence) in the (vi,j) based on the process, procedures,
methods, device, etc. for each (vi,j)
Individual Exposure Health Risk Index (IEHRI) (exposure) =
[(v1,1)(CF1,1)(WF1,1) + (v1,2)(CF1,2)(WF1,2) + … + (v1,j)(CF1,j)(WF1,j)]
Individual Exposure Health Risk Profile (IEHRP) =
[(v1,1)(CF1,1)(WF1,1) + (v1,2)(CF1,2)(WF1,2) + (v1,3)(CF1,3)(WF1,3)] ,
[(v2,1)(CF2,1)(WF2,1) + (v2,2)(CF2,2)(WF2,2) + (v2,3)(CF2,3)(WF2,3)],
…..… ,
[(vi,1)(CFi,1)(WFi,1) + (vi,2)(CFi,2)(WFi,2) +…+ (vi,,j)(CFi,,j)(WFi,,j)]
11
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
2 2
3
1
IEHRP Visualization & Normalization
X
RADONNOISE BENZENE
MEASURED
EXPOSURE
Genetics
Medical Record
GLUTEN
Graphing the raw data we get the following IERHP.
However, to address censored data requires -
Normalization
= censored data
12
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
IEHRP Visualization & Normalization
IEHRP
= (IEHRI1 , IEHRI2 , IEHRI3, IEHRI4 )
= ([v1,1 + v1,2 + v1,3 ] , [v2,1 + v2,2 + v2,3] , [v3,1 + v3,2 + v3,3] , [v4,1 + v4,2 + v4,3 ])
= ([1 + 1 + 1] , [1 + (-) + 1] , [1 + 1+ (-)] , [(-) + (-) + 1])
= (3, 2, 2, 1)
Normalization Factors w.r.t. censored values in each IEHRI
Normalized IEHRI1 = (1/3) IEHRI1 = (1/3) [1 + 1 + 1] = 1
Normalized IEHRI2 = (1/2) IEHRI2 = (1/2) [1 + 0 + 1] = 1
Normalized IEHRI3 = (1/2) IEHRI3 = (1/2) [1 + 1 + 0] = 1
Normalized IEHRI4 = (1/1) IEHRI4 = (1/1) [0 + 0 + 1] = 1
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
1 11 1
IEHRP Visualization & Normalization
X
RADONNOISE BENZENE
MEASURED
EXPOSURE
Genetics
Medical Record
GLUTEN
Normalization = all indices will have values between 0
and 1. Accounting for the censored data we get the
following IEHRP
14
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Values and Factors Matrices
Modified values
Sum row entries
to produce indices =
IEHRI1
IEHRI2
IEHRI3
IEHRI4
Hadamard product is entry-wise multiplication
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Values and Factors Matrices
Modified values
Sum row entries
to produce indices =
IEHRI1
IEHRI2
IEHRI3
IEHRI4
Hadamard product is entry-wise multiplication
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
More Values and Indices
=
IEHRI1
…….
……..
IEHRIm
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Matrix Notation
column vector of
indices
matrix multiplication
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
IEHRP Benefits: Example
A
B
“Policymaker”“Healthcare Provider”
NOISE BENZENE GLUTEN RADON
NOISE BENZENE GLUTEN RADON
NOISE GLUTEN RADON BENZENE
RADON NOISE BENZENE GLUTEN
19
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Conclusion…
• Total Exposure Health can:
• Drive the development of medical expert systems, sensors and R&D
• Advance the science and understand the effects of currently undetectable exposures
and what we clinically know about exposure, gene expression, and disease
• Through the IEHRP:
• All information integrated about an individual
• Area sensors, Personnel/Physiological Sensors…integrated with all genetics, previous exposures
• Genomic data will be transparently incorporated into the clinical decision process
• Collectively
• Patients/providers will be afforded data real-time into healthcare enhancing the
Doctor/Patient experience
• Incrementally maximize human performance to not only retain personal health
attributes but enhance them
20
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
QUESTIONS?
Mark Oxley, PhD
Professor of Mathematics
Air Force Institute of Technology (AFIT)
Office: 1-937-255-3636 ext. 4515
Mark.oxley@afit.edu
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
BACKUP
22
AFIT Education Excellence:
Inspiration  Imagination  Innovation  Invention  Implementation  Impact
Noise Exposure Demonstration Project (NEDP)

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Revolutionizing Precision Medicine w/Big Data The Individual Exposure Health Risk Profile (IEHRP)

  • 1. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Revolutionizing Precision Medicine w/Big Data The Individual Exposure Health Risk Profile (IEHRP) INFORMS Healthcare 2019 Richard Hartman, PhD Mark Oxley, PhD Professor of Mathematics Department of Mathematics and Statistics Graduate School of Engineering and Management Air Force Institute of Technology (AFIT) Wright-Patterson AFB, OH 29 Jul 2019
  • 2. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Disclosures • Presenter has no interest to disclose. • No discussion of off-label uses • The views expressed are those of the author and do not necessarily reflect the official policy or position of the Air Force, the Department of Defense, or the U.S. Government.
  • 3. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Imagine If… Doctors could understand the effects of exposures on a patients health throughout their life Identify diseases at the molecular level before the onset of disease Enable rapid interventions and supportive medical care Reduce disability by truly preventing disease Demonstrate significant cost savings and efficiencies 3
  • 4. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Total Exposure Health TEH Overview TEH aims to capture workplace, environmental & lifestyle exposures to the individual (i.e., N=1, genome) using advances in science, technology & informatics to prevent disease; improve health and well-being: Healthiest Performing Population by 2025 E H Increase use of genomic research and knowledge Improve exposure monitoring through sensors and wearables Better understanding of monitored exposure to performance and individual health outcomes Advance operational decisions using advancements in science, medicine, technology, and informatics with digital biodata bank, Big Data analytics, and expert systems Total Exposure Health (TEH) represents a paradigm shift in military medicine – from a primary focus on disease and injury treatment to a more holistic approach that focuses on health and prevention. 4
  • 5. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Reimagining Healthcare with TEH TEH will bring together distinct systems and initiatives into one portfolio: integrating exposure science, information technology, and existing healthcare programs to develop end-to-end systems. TEH capabilities will maximize the value of these advances by translating data collection, analysis, management, and visualization into clinically and personally actionable results. 5
  • 6. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact INDIVIDUAL EXPOSURE HEALTH RISK INDEX/PROFILE (IEHRI/P)
  • 7. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Our Clinical Disposition Individual Exposure Health Risk Index/Profile (IEHRI/P) Our Unique Genetic Proclivity IEHRI/P: Individual Exposure Indices/Profile Our Exposures 7
  • 8. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact IEHRI/P: Expressed Mathematically IEHRI IEHRP 8 Individual Exposure Health Risk Profile (IEHRP) = (IEHRI 1, IEHRI 2 ,…, IEHRI i ) = ([v1,1 + v1,2 + v1,3 ], [v2,1 + v2,2 + v2,3] ,…, [vi,1 + vi,2 + vi,3])
  • 9. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Visualizing the IEHRP – Individual IEHRP will aid in visualizing an individual’s unique exposure susceptibilities Lee NOISE BENZENELEAD RADIATION GLUTEN SUSCEPTABILITY HIGH LOW
  • 10. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact IEHRI with Multiple Variables • Limitations to the IEHRI became evident, which only accounted for three variables to describe an individual exposure. • This required the IEHRP to be modified so it could account for multiple confounding factors IEHRP = (IEHRI1 , IEHRI2 , … , IEHRIj ) = ([v1,1 + v1,2 + v1,3 +…+ v1,j ] , [v2,1 + v2,2 + v2,3 +…+ v2,j ] , … , [vi,1 + vi,2 + vi,3 +…+ vi,j ]) Genetics Diagnostics Sensors and Mobile Data Lifestyle Occupation Medical History Environment Family History
  • 11. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact IEHRI & IEHRP: Expanded IEHRP  IEHRI – Which vi,j value is more important?  WFi,j = weighting factor– importance of each variable (vi,j) when compared with all the variables with in the IEHRI (e.g., are genes more important than exposure measure?)  CFi,j = correction factor – variability (confidence) in the (vi,j) based on the process, procedures, methods, device, etc. for each (vi,j) Individual Exposure Health Risk Index (IEHRI) (exposure) = [(v1,1)(CF1,1)(WF1,1) + (v1,2)(CF1,2)(WF1,2) + … + (v1,j)(CF1,j)(WF1,j)] Individual Exposure Health Risk Profile (IEHRP) = [(v1,1)(CF1,1)(WF1,1) + (v1,2)(CF1,2)(WF1,2) + (v1,3)(CF1,3)(WF1,3)] , [(v2,1)(CF2,1)(WF2,1) + (v2,2)(CF2,2)(WF2,2) + (v2,3)(CF2,3)(WF2,3)], …..… , [(vi,1)(CFi,1)(WFi,1) + (vi,2)(CFi,2)(WFi,2) +…+ (vi,,j)(CFi,,j)(WFi,,j)] 11
  • 12. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact 2 2 3 1 IEHRP Visualization & Normalization X RADONNOISE BENZENE MEASURED EXPOSURE Genetics Medical Record GLUTEN Graphing the raw data we get the following IERHP. However, to address censored data requires - Normalization = censored data 12
  • 13. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact IEHRP Visualization & Normalization IEHRP = (IEHRI1 , IEHRI2 , IEHRI3, IEHRI4 ) = ([v1,1 + v1,2 + v1,3 ] , [v2,1 + v2,2 + v2,3] , [v3,1 + v3,2 + v3,3] , [v4,1 + v4,2 + v4,3 ]) = ([1 + 1 + 1] , [1 + (-) + 1] , [1 + 1+ (-)] , [(-) + (-) + 1]) = (3, 2, 2, 1) Normalization Factors w.r.t. censored values in each IEHRI Normalized IEHRI1 = (1/3) IEHRI1 = (1/3) [1 + 1 + 1] = 1 Normalized IEHRI2 = (1/2) IEHRI2 = (1/2) [1 + 0 + 1] = 1 Normalized IEHRI3 = (1/2) IEHRI3 = (1/2) [1 + 1 + 0] = 1 Normalized IEHRI4 = (1/1) IEHRI4 = (1/1) [0 + 0 + 1] = 1
  • 14. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact 1 11 1 IEHRP Visualization & Normalization X RADONNOISE BENZENE MEASURED EXPOSURE Genetics Medical Record GLUTEN Normalization = all indices will have values between 0 and 1. Accounting for the censored data we get the following IEHRP 14
  • 15. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Values and Factors Matrices Modified values Sum row entries to produce indices = IEHRI1 IEHRI2 IEHRI3 IEHRI4 Hadamard product is entry-wise multiplication
  • 16. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Values and Factors Matrices Modified values Sum row entries to produce indices = IEHRI1 IEHRI2 IEHRI3 IEHRI4 Hadamard product is entry-wise multiplication
  • 17. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact More Values and Indices = IEHRI1 ……. …….. IEHRIm
  • 18. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Matrix Notation column vector of indices matrix multiplication
  • 19. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact IEHRP Benefits: Example A B “Policymaker”“Healthcare Provider” NOISE BENZENE GLUTEN RADON NOISE BENZENE GLUTEN RADON NOISE GLUTEN RADON BENZENE RADON NOISE BENZENE GLUTEN 19
  • 20. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Conclusion… • Total Exposure Health can: • Drive the development of medical expert systems, sensors and R&D • Advance the science and understand the effects of currently undetectable exposures and what we clinically know about exposure, gene expression, and disease • Through the IEHRP: • All information integrated about an individual • Area sensors, Personnel/Physiological Sensors…integrated with all genetics, previous exposures • Genomic data will be transparently incorporated into the clinical decision process • Collectively • Patients/providers will be afforded data real-time into healthcare enhancing the Doctor/Patient experience • Incrementally maximize human performance to not only retain personal health attributes but enhance them 20
  • 21. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact QUESTIONS? Mark Oxley, PhD Professor of Mathematics Air Force Institute of Technology (AFIT) Office: 1-937-255-3636 ext. 4515 Mark.oxley@afit.edu
  • 22. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact BACKUP 22
  • 23. AFIT Education Excellence: Inspiration  Imagination  Innovation  Invention  Implementation  Impact Noise Exposure Demonstration Project (NEDP)

Editor's Notes

  1. Maximizes human performance to not only retain personal health attributes but enhance them Helps Providers understand the effects of exposures on a patients health now and throughout their life (“True Comprehensive Health Surveillance”) Enables understanding of the effects of currently undetectable exposures and what we clinically know about exposure, gene expression, and disease Enables rapid, proactive intervention and supportive medical care Leads to significant savings in total health care costs
  2. The Air Force is dedicated to being the “healthiest and highest performing segment of the US by 2025” but the AFMS can only achieve Healthiest Population by true prevention - available like never before due to advances in science, technology, and medicine. Total Exposure Health positions the AFMS to to meet this vision with emphasis on “Personalized Healthcare” going beyond healing the ill and preventing early disease. A bold and novel concept, TEH associates exposures to the lowest common denominator – the individual’s DNA (N=1) – enriching operational decisions with forward vision using advancements in science, technology, and informatics to maximize Human Performance and advance the health and well-being of ALL Air Force beneficiaries. New knowledge of the relationships between individual’s genetic predispositions, epigenetic factors, and exposure to chemicals from lifestyle, occupation, and the environment can now support development of diagnostic approaches, treatment methods, and intervention strategies that consider all variables collectively. Hence, a comprehensive understanding of multiple exposures with genomic information will support a necessary paradigm shift from healthcare to health by promoting more rapid identification of risks to health and well-being and enabling earlier and more tailored interventions. Accurate calculation of disease risk factors will involve developing diagnostic systems that merge genomics to find relationships at the individual level to inform risk of disease promote health and well-being through intervention and mitigation of these risks along with various BigData from sensors, medical records, and various disparate unstructured data sets in order to understand the root causes of injury and disease and truly implement primary prevention.
  3. Rethinking Exposure we need a way to accesses, manage, mitigate and communicate. This is accomplished through the concept of the Individual Exposure Health Risk Profile.
  4. Typical “Dose vs. Effect” exposure curve and verbiage CLICK 1: We expect most individuals of a population to fall along this curve… CLICK 2: Specific Exposure #1: Noise (Lily is susceptible) CLICK 3: Specific Exposure #2: Benzene (Kirk is susceptible) CLICK 4: Specific Exposure #3: Lead (Al is susceptible) CLICK 5: Specific Exposure #4: Radiation (Rich is susceptible) CLICK 6: Specific Exposure #5: Gluten (Amy is susceptible) CLICK 7: Finally, we layer these exposures demonstrating that all individuals are unique…
  5. The Individual data will: Aggregate will help to better understand current and emerging trends through studies and analyses to advance primary prevention Advance Medicine through Research & Development (R&D) Ensure compliance with regulatory standards Improve quality of care and encourage good lifestyle choices Through TEH we will leverage and advance exposure science, sensor and data technologies, health informatics, and clinical support systems as a cutting edge way to obtain a holistic understanding of an individual’s health, root causes of disease and injury, and innovative but accessible methods for primary prevention to include: R&D to expand TEH capabilities into sensor, informatics, and database platforms Infrastructure, resources, and activities management Military, public, academic, and private partnerships Care provider, workforce, and patient training Enhanced support, ancillary services and benefits Healthcare delivery towards primary prevention Organizational change and Military Readiness supported by validated data Data integration into Individual Longitudinal Exposure Records (ILER)