>>GOOD MORNING, EVERYBODY.
IT'S 8:59.
I THINK WE SHOULD GET STARTED
FOR THE DAY.
WE HAVE A LONG DAY, WE HAVE A
FULL DAY.
LIKE YESTERDAY, TODAY WE WILL
START WITH TALKS ON SICKLE CELL
DISEASE SURVEILLANCE SYSTEMS AND
THEN WE WILL GO TO
IMPLEMENTATION AND ON FOR OTHER
TALKS FOR SYMPOSIUM 3 AND 4.
SO WITHOUT ANY FURTHER DELAYS, I
WILL ASK ALEX TO GIVE US SOME
LOGISTICS, QUICKLY SHE'S GOING
TO GO OVER LOGISTICS IN A MINUTE
OR SO, AND THEN AFTER THAT, WE
WILL GET STARTED.
DR. MARY HULIHAN IS GOING TO
START THE SESSION.
ALEX?
>> THANK YOU.
WELCOME TO DAY TWO.
WE HOPE YOU ENJOYED YESTERDAY.
WE DO WANT TO GO OVER A FEW
HOUSEKEEPING THROUGHOUT THE
DURATION OF THE WORKSHOP.
ATTENDEES SHOULD HAVE RECEIVED A
UNIQUE LOG-IN FOR ATTENDEES
SPECIFICALLY THIS MORNING.
YOU CAN USE THAT ALL THREE DAYS
OF THE WORKSHOP.
WITH THAT BEING SAID, THIS
MEETING IS BEING RECORDED.
IF YOU DO NEED CLOSED
CAPTIONING, IT'S LOCATED AT THE
BOTTOM OF YOUR SCREEN.
PLEASE CLICK ON "LIVE
CAPTIONING," THEN CLICK ON" SHOW
SUBTITLES."
WE DO ASK ATTENDEES INTERACT
THROUGHOUT THE WORKSHOP.
WITH THAT BEING SAID, WE HAVE A
Q & A BOX AT THE BOTTOM OF THE
SCREEN IF YOU WOULD LIKE TO ASK
QUESTIONS TO SPEAKERS, PLEASE
INPUT YOUR QUESTIONS THERE.
IF YOU WOULD LIKE TO HAVE CHAT
OR CONVERSATION, PLEASE USE THE
CHAT BOX FOR THAT.
ONCE AGAIN, THIS MEETING IS
BEING RECORDED.
IF YOU DO HAVE ANY QUESTIONS,
PLEASE REACH OUT TO ME.
I WILL BE HERE THROUGHOUT THE
DURATION ONLINE.
ONCE AGAIN, IF YOU HAVE ANY
QUESTIONS, PLEASE REACH OUT.
WE DO ASK THAT ALL ATTENDEES
REMAIN MUTED AND KEEP THEIR
CAMERAS OFF AND WE HOPE YOU
ENJOY DAY 2.
THANK YOU.
>> THANK YOU, ALEX.
AND I WILL NOW HAND OVER THE
SESSION TO DR. HULIHAN.
>> THANK YOU SO MUCH, AND THANK
YOU FOR THE KIND INVITATION TO
BE HERE AND SPEAK WITH YOU
TODAY.
WE'RE REALLY EXCITED TO SHARE
WITH YOU SOME INFORMATION ABOUT
OUR SICKLE CELL DATA COLLECTION
PROGRAM, OUR SURVEILLANCE SYSTEM
FOR SCDC AND WE'RE GOING TO HAVE
A NUMBER OF PRESENTERS TODAY.
I'M NOT SURE IF YOU CAN PULL UP
MY SLIDES?
WONDERFUL, AND GO TO THE NEXT
SLIDE, PLEASE.
SO A QUICK OVERVIEW OF THE
PROGRAM.
THAT WE'LL BE SHARING
INFORMATION FROM TODAY.
THIS IS A COOPERATIVE AGREEMENT
THAT IS FUNDED THROUGH THE
CENTERS FOR DISEASE CONTROL AND
PREVENTION AND WE CURRENTLY HAVE
11 STATES PARTICIPATING IN THE
PROGRAM.
YOU CAN SEE THEM LISTED THERE ON
THE RIGHT, AND ALL OF THE STATES
ARE COLLECTING DATA.
THEY ARE PRESENTING AND PULLING
TOGETHER AGGREGATE INFORMATION,
ALL OF WHICH IS GOING TO BE
AVAILABLE ON OUR WEBSITE VERY
SOON.
AND ACROSS THOSE 11 STATES BASED
ON THE U.S. CENSUS DATA, WE
THINK THAT THERE'S APPROXIMATELY
A THIRD OF THE U.S. SICKLE CELL
DISEASE POPULATION.
FIVE OF THESE 11 STATES ARE ALSO
FUNDED TO DO ADDITIONAL ANALYSES
AND THAT'S WORK THAT'S GOING TO
BE SHARED WITH YOU TODAY.
SO JUST A QUICK OVERVIEW AND NOT
TO GO INTO TOO MUCH DETAIL ABOUT
THIS, BUT A REMINDER THAT THIS
IS A SURVEILLANCE SYSTEM AND SO
THE INFORMATION THAT WILL BE
PRESENTED TODAY COMES FROM A LOT
OF DIFFERENT DATA SOURCES THAT
IS ALL LINKED TOGETHER.
YOU CAN SEE THOSE DATA SOURCES
LISTED HERE.
SOME OF THE ANALYSES THAT ARE
PRESENTED USE SOME OF THESE DATA
SOURCES, SOME USE ALL OF THEM,
BUT THE SPEAKERS WILL SHARE WITH
YOU WHICH ARE THE SOURCES FOR
THE INFORMATION THEY'RE
PROVIDING.
SO TODAY'S PRESENTATIONS ARE
GOING TO COVER A WIDE VARIETY OF
TOPICS ALL OF WHICH ARE
REFLECTED ON THE SLIDES YOU JUST
SAW.
WE'RE GOING TO START WITH THE
SCDC MODERNIZATION AND MOVE TO
NORTH CAROLINA, TALK ABOUT
HEALTHCARE UTILIZATION.
CALIFORNIA IS GOING TO SHARE
INFORMATION ABOUT ACCESS TO
HEALTHCARE.
THE MICHIGAN TEAM IS GOING TO
TALK ABOUT HOW THEY'RE USING THE
DATA TO IMPROVE HEALTHCARE
POLICY, AND THEN WE'LL CLOSE OUT
WITH GEORGIA TALKING ABOUT SOME
OF THE WORK WE'VE DONE TO LINK
THIS SURVEILLANCE DATA WITH
COVID-19 DATA SYSTEMS.
THEN WE'LL HAVE TIME AT THE END
FOR SOME QUICK Q & A.
SO JUST A QUICK REMINDER, WE
HAVE JUST POSTED A NEW
FORECASTED FUNDING OPPORTUNITY.
YOU CAN GO TO GRANTS.GOV AND
FIND IT THERE.
AND IF YOU'D LIKE TO STAY UP TO
DATE ON THE HAPPENINGS OF THIS
PROGRAM, WE HAVE A QUARTERLY
NEWSLETTER THAT YOU CAN
SUBSCRIBE TO, IT'S ON THE
WEBPAGES, THERE'S A QUICK LINK
TO SUBSCRIBE YOU AND YOU'LL GET
UPDATES DELIVERED TO YOUR INBOX
EVERY QUARTER.
SO WITH THAT, I THINK WE CAN
MOVE OVER TO DR. HANKINS WITH
THE TENNESSEE TEAM.
>> THANK YOU, DR. HULIHAN, AND
THANK YOU, FOR THE INTRODUCTION.
I AM GOING TO SHARE MY SCREEN
AND BEGIN MY PRESENTATION.
I AM GOING TO DISCUSS -- CAN YOU
SEE MY SLIDES?
>> YES, WE CAN.
>> OKAY, THANK YOU.
SO I WILL DISCUSS THE DATA
MODERNIZATION IN OUR APPROACH TO
BUILDING A SURVEILLANCE PROGRAM.
SO I WILL BEGIN BY DISCUSSING
THE GAPS IN HAVING BIG DATA IN
SICKLE CELL DISEASE.
OUR CURRENT APPROACHES TO THE
MODERNIZATION IN SICKLE CELL
DISEASE USING SURVEILLANCE.
WHY WE NEED A SICKLE CELL DATA
COLLECTION SURVEILLANCE PROGRAM,
AND HOW WE ARE APPROACHING
SURVEILLANCE IN FUTURE
DIRECTIONS.
SO ALTHOUGH ALL 50 STATES IN THE
UNITED STATES DO HAVE NEWBORN
SCREENING, IT'S UNIVERSAL, VERY
FEW STATES ARE USING THE
EPIDEMIOLOGIC DATA THAT THE
NEWBORN SCREENING PROVIDES, AND
WE ALSO HAVE GOVERNMENT FUNDED
PROGRAMS SUCH AS MEDICAID AND
MEDICARE THAT HAVE A WEALTH OF
DATA THAT IS CURRENTLY BEING
UNDERUTILIZED FOR RESEARCH AND
OTHER EPIDEMIOLOGICAL PURPOSES.
AND WHAT THAT RESULTS IS THAT WE
REALLY DO NOT HAVE A
POPULATION-LEVEL DATA FOR SICKLE
CELL DISEASE, WHICH REALLY
IMPAIRS OUR ABILITY TO CALCULATE
DISEASE PREVALENCE, DELIVERY OF
EVIDENCE-BASED CARE, AND
HEALTHCARE UTILIZATION IN THE
UNITED STATES.
THERE ARE CURRENT APPROACHES TO
BIG DATA IN SICKLE CELL DISEASE
CURRENTLY.
FOR EXAMPLE, THERE ARE
ELECTRONIC HEALTH RECORD
COLLABORATIVES SUCH AS THE ASH
DATA HUB THAT YOU WILL HEAR
LATER THIS MORNING, THERE ARE
MULTI-REGISTRY DEVELOPMENTS SUCH
AS THE SICKLE CELL DISEASE
IMPLEMENTATION CONSORTIUM THAT
YOU WILL HEAR IN THE NEXT
SESSION.
THERE ARE LARGE SYSTEMS THAT
USES SINGLE DATABASES SUCH AS
KAISER PERMANENTE AND VETERANS
AFFAIRS, AND THERE ARE SINGLE
CENTER REGISTRIES THAT EVEN
THOUGH SOME OF THEM DO HAVE A
LOT OF PATIENTS, THEY'RE NOT
CONSIDERED BIG DATA.
THE PROBLEM WITH ALL OF THEM IS
THAT THEY ARE NOT REALLY
POPULATION-LEVEL DATA BECAUSE
THEY DO NOT ENCOMPASS THE ENTIRE
POPULATION.
ALTHOUGH THEY'RE ALL VERY
IMPORTANT.
SO IN THIS FIGURE HERE THAT WE
PUBLISHED LAST YEAR SHOWS THE
RELATIONSHIP BETWEEN
POPULATION-LEVEL DATA WITH THE
OTHER TYPES OF REGISTRIES THAT
EXIST.
SO IF YOU LOOK AT THE DARK GREEN
CIRCLE, WE CALL IT A POPULATION
SURVEILLANCE, THAT IS
POPULATION-LEVEL DATA AND
ENCOMPASSES ALL THE OTHER
REGISTRIES AND THE
SUBPOPULATIONS THAT REGISTRIES,
FOR EXAMPLE, ENCOMPASS.
SO IN ESSENCE, THE WAY TO
UNDERSTAND IT IS THAT COHORT
STUDIES AND REGISTRIES, FOR
EXAMPLE, EVEN THOUGH THEY MAY BE
MULTISITE, MULTICENTER, THEY'RE
A SUBSET OF THE POPULATION LEVEL
DATA THAT SURVEILLANCE PROGRAMS
CAN PROVIDE.
SO BY HAVING POPULATION-LEVEL
DATA, BY HAVING A SURVEILLANCE
PROGRAM, WE'LL BE ABLE TO
ESTIMATE THE TRUE PREVALENCE OF
A DISEASE AND ITS COMPLICATIONS.
THE GEOGRAPHIC DISTRIBUTION OF
ALL CASES, WE'LL BE ABLE TO
MONITOR POPULATION MOVEMENT AS
PEOPLE MOVE FROM ONE STATE OR
ONE CITY TO THE OTHER.
IDENTIFY AREAS WHERE CLINICIANS
ARE NEEDED OR MORE CLINICS ARE
NEEDED.
AND THEN MONITOR HEALTHCARE
UTILIZATION ACROSS MULTIPLE
INSTITUTIONS AND BE ABLE TO MAKE
COMPARISONS.
THERE ARE A VARIETY OF BARRIERS
FOR US TO BUILD SURVEILLANCE
SYSTEMS.
FOR EXAMPLE, THERE ARE MULTIPLE
DATA SOURCES THAT COMPRISE A
SURVEILLANCE SYSTEM.
AND MOST OF THE TIME, THEY'RE
NOT LINKED.
THE OWNERSHIP OF THOSE DATASETS
IS VARIABLE, SO DIFFERENT PEOPLE
OWN DIFFERENT DATA.
AND THEN VARIABLE QUALITY OF
THOSE DATASETS, NOT ALL DATASETS
ARE RESEARCH-READY.
AND THEN TO ACCESS THOSE
DATASETS, IT CAN BE CUMBERSOME.
IT CAN BE A LONG, BUREAUCRATIC
PROCESS THAT CREATES A SLOW
ACCESS ROAD, AND IT TAKES TIME
TO COMPILE AND VALIDATE THIS
DATASET.
SO OUR APPROACH, THE SCDC
APPROACH TO BUILD
POPULATION-LEVEL DATA OR
SURVEILLANCE PROGRAM IS TO APPLY
SIMILAR PRINCIPLES ACROSS ALL
PARTICIPATING STATES IN WHAT WE
CALL A DISTRIBUTED DATA NETWORK,
WHICH I WILL DISCUSS IN A FEW
SLIDES.
BUT WHAT IT TAKES TO DO THIS
TOGETHER IS THAT WE HAVE TO
BUILD A RELATIONSHIP ACROSS ALL
STATE, ALL THE PARTICIPANTS, WE
HAVE TO STANDARDIZE THE DATA, WE
HAVE TO CREATE A
MULTIDISCIPLINARY APPROACH.
IT TAKES DIFFERENT TYPES OF
PEOPLE WITH DIFFERENT EXPERTISE
TO CREATE A SURVEILLANCE PROGRAM
AND SOMETIMES WE NEED AN HONEST
BROKER WHO IS AN IMPARTIAL
MEDIATOR TO ALLOW US ACCESS TO
DIFFERENT TYPES OF DATA.
AND BECAUSE THERE IS VARIABILITY
IN WHO HO OWNS THE DATA IN WHICH
STATE AND FORMAT THE DATA STORED
IN DIFFERENT STATES, THERE'S
SOME VARIABILITY IN THE APPROACH
TO CREATING A DISEASE
SURVEILLANCE PROGRAM.
SO FOR EXAMPLE, NEWBORN
SCREENING AND MEDICAID DATA,
THEY ARE IN DIFFERENT FORMATS IN
DIFFERENT STATES SO IN THE ONE
SCREEN DATA FORMAT IN TENNESSEE
IS DIFFERENT THAN WHAT IT WOULD
LOOK LIKE IN GEORGIA OR NORTH
CAROLINA, FOR EXAMPLE.
SO EACH STATE EULSES A UNIQUE
DATA FLOW AND WHAT I'M SHOWING
YOU HERE ON THIS FIGURE IS THE
APPROACH TO THE DATA FLOW IN THE
STATE OF TENNESSEE.
SO FOR EXAMPLE, WE BEGAN BY
MERGING VITAL STATISTICS DATA
WITH HOSPITAL UT UTILIZATION DAA
AND MEDICAID DATA.
ONCE THESE THREE DATASETS ARE
LINKED, THEN WE LINKED WITH
NEWBORN SCREENING DATA AND ONLY
THEN WE'RE ABLE TO LI LINK WITH
CLINIC-LEVEL DATA AND LOCAL
REGISTRIES.
ONCE THIS IS DONE, WE CAN
ANALYZE THE DATA AND REPORT.
AND THE WAY WE REPORT IS BY
USING A COMMON DATA MODEL WHICH
I WILL EXPLAIN NEXT.
THOSE THREE OTHER EXAMPLES ARE
THE DATA FLOW FOR GEORGIA,
COLORADO, AND NORTH CAROLINA.
GEORGIA AND NORTH CAROLINA ARE
ON THE LINE, AND THEY WILL GIVE
MORE DETAILS AND ALSO YOU CAN
ASK MORE QUESTIONS ABOUT THE
PROCESS IN DIFFERENT STATES.
THE DATA VALIDATION AND
STANDARDIZATION OF THE DATA ALSO
FOLLOWS A PROCESS THAT WAS
AGREED UPON IN OUR GROUP, SO THE
CASE IDENTIFICATION, THIS IS AN
EXAMPLE OF NORTH CAROLINA, THEY
USE LEVEL 2 IDENTIFICATION OF
THREE ENCOUNTERS FOR SICKLE CELL
DISEASE OVER FIVE YEARS.
HERE ON THE RIGHT, EXAMPLE OF
DATA LINKAGE AND DEDUPLICATION
FROM GEORGIA BEGINS WITH
CLEANING, DEDUPLICATING AND
STANDARDIZING THE DATASET.
THEN AS I MENTIONED WE FOLLOW A
COMMON DATA MODEL WHICH IS A
STANDARD VARIABLE FORMAT THAT --
A DICTIONARY WE CREATED FOR THIS
PROJECT.
WE DECIDED WHICH VARIABLES THAT
WE WANT TO INCLUDE, HOW THEY
WILL BE NAMED, HOW THEY WILL BE
FORMATTED, AND THEN EACH STATE
CREATE A DATASET THAT HAS THE
SAME VARIABLES, THE SAME
VARIABLE NAMES AND FORMATS.
WE ADOPT A COMMON DATA MODEL
THAT MAKES IT A LOT EASIER FOR
US TO EXCHANGE DATA AT THE END.
THE COMMON DATA MODEL IS ONE
SINGLE DA DATA INSTRUMENT AND OE
YOU AGREE ON THOSE STANDARD WAYS
OF NAMING THE VARIABLES AND
STRUCTURING THE VARIABLES, IS
THAT WE CAN EXPAND TO ADDITIONAL
DATASETS.
SO HERE'S IN THE PICTURE AN
EXAMPLE OF THE COORDINATED
SURVEILLANCE DATA WE HAVE, BUT
WE CAN EXPAND TO HEALTH
OUTCOMES, PHARMACY DATA AND
OTHER TYPES OF DATASETS, ALL
FOLLOWING THE SAME COMMON DATA
MODEL.
AND WE ARE IMPLEMENTING A
FEDERATED MODEL WHERE DATA ARE
MAINTAINED LOCALLY BY EACH SITE.
AND THIS IS WHAT I'M SHOWING YOU
IN THIS SLIDE.
THE DISTRIBUTED DATA NETWORK
THAT WE ESTABLISHED IS THAT EACH
SITE, EACH STATE IS AN EQUAL
PARTNER, SHOWN HERE IN THE
BOTTOM LEFT OF THE PICTURE.
SO WE ALL FOLLOW A COMMON DATA
MODEL AND THEN EACH SITE OWNS
THE DATA, AND THEN THERE'S A
LEAD CENTER THAT QUERIES THIS
DATA AND THE STATES CAN SEND
AGGREGATED RESULTS AT THE END,
BUT THE DATA BELONGS, IS OWNED,
BY EACH SITE OR EACH STATE.
AND THEN THIS PICTURE ON THE
LEFT, I'M SHOWING THE 11 STATES
THAT CURRENTLY HAVE A
SURVEILLANCE PROGRAM AND
DR. HULIHAN SHOWED THIS PICTURE
BUT THE POINT IS TO SHOW THE
PICTURE ON THE RIGHT, WHICH IS
THE MAP OF THE UNITED STATES
SHOWING THE PREVALENCE OF SICKLE
CELL DISEASE IN OUR COUNTRY, AND
WHAT IS THE POINT HERE IS THAT
THE SURVEILLANCE PROGRAM IS
BEGINNING TO NOW EXTEND TO STATE
WHERE THE PREVALENCE IS THE
HIGHEST, THE PREVALENCE OF
SICKLE CELL DISEASE IS THE
HIGHEST.
SO LITTLE BY LITTLE, WE'RE
BEGINNING TO COVER ALL STATES
AND LITERALLY HAVE
POPULATION-LEVEL DATA.
SO THE NEXT STEPS ARE HOPEFULLY
TO EXPAND TO MORE STATES, WHICH
HOPEFULLY ALL 50 STATES ONE DAY
WILL HAVE A SURVEILLANCE
PROGRAM, SO WE'LL HAVE A TRUE
POPULATION COVERAGE,
POPULATION-LEVEL COVERAGE OF
SICKLE CELL DISEASE IN THE
COUNTRY.
AND THEN EXPAND TO OTHER DATA
SOURCES, SO FOR EXAMPLE,
MEDICARE DATA IS VERY EXPENSIVE
TO ACCESS.
SO HOPEFULLY THAT WILL BE
INCLUDED IN THE SURVEILLANCE
PROGRAM.
ACADEMIC, ENVIRONMENTAL DATA, ET
CETERA.
AND HOPEFULLY WE CAN MAKE THIS
PROCESS SIMPLE.
ONE EXAMPLE IS PERHAPS USING
PUBLIC HEALTH AUTHORITY IN MORE
AND MORE STATES THAT HAVE
DIFFICULTY ACCESSING THE DATA,
AND THE PUBLIC HEALTH AUTHORITY
FOR THOSE WHO DON'T KNOW IS A
RULE THAT PERMITS ENTITIES TO
DISCLOSE PROTECTED HEALTH
INFORMATION WI WITHOUT
AUTHORIZATION, SO FOR EXAMPLE,
WITHOUT IRB APPROVAL,
SPECIFICALLY USED FOR PUBLIC
HEALTH PURPOSES.
AND ALSO MORE BUY-IN FROM
GOVERNMENT AGENCIES ALSO
IMPROVES THE ABILITY FOR US TO
ACCESS DIFFERENT TYPES OF DATA.
SO WITH THAT, I'M GOING TO END
AND TURN IT BACK TO DR. HULIHAN.
THANK YOU.
>> THANK YOU SO MUCH,
DR. HANKINS.
SO FOR OUR NEXT PRESENTATION
TODAY, WE'RE GOING TO HAVE
DR. MARIAM KAYLE FROM THE NORTH
CAROLINA SCDC TEAM.
SHE'S GOING TO BE PRESENTING ON
THE HEALTHCARE UTILIZATION
INFORMATION THAT HAS BEEN PULLED
FROM THIS DATASET IN THE STATE
OF NORTH CAROLINA.
SO MARIAM?
>>HELLO, EVERYONE.
MY NAME IS MARIAM KAYLE.
THANK YOU SO MUCH FOR THE
INVITATION.
I'M REALLY EXCITED TO PRESENT
THE NORTH CAROLINA SICKLE CELL
DATA COLLECTION PROGRAM AND
SHARE WITH YOU SOME OF THE WORK
THAT WE HAVE BEEN DOING ON
UNDERSTANDING HEALTHCARE
UTILIZATION IN OUR STATE.
THESE ARE MY DISCLOSURES.
OUR FUNDING FROM THE CDC AND THE
PRESENTATION TODAY REPRESENTS MY
VIEWS AND NOT THE NORTH CAROLINA
DEPARTMENT OF HEALTH AND HUMAN
SERVICES.
SO A LITTLE BIT ABOUT OUR
PROGRAM.
OUR PROGRAM IS A LITTLE BIT
DIFFERENT AND UNIQUE THAN THE
OTHER STATE IN THAT WE HAVE A
REALLY CLOSE COLLABORATION
BETWEEN DUKE UNIVERSITY SCHOOL
OF NURSING AND THE NORTH
CAROLINA DEPARTMENT OF HEALTH
AND HUMAN SERVICES, DIVISION OF
PUBLIC HEALTH.
WE ALSO HAVE ESTABLISHED
COLLABORATIONS ACROSS THE STATE
WITH DIFFERENT ENTITIES THAT ARE
INVOLVED IN SICKLE CELL DISEASE,
INCLUDING PIEDMONT HEALTH
SERVICES AND SICKLE CELL AGENCY,
A COMMUNITY-BASED ORGANIZATION
ACROSS NORTH CAROLINA, THE
GOVERNOR'S APPOINTED COUNCIL ON
SICKLE CELL DISEASE, AND WE HAVE
COLLABORATIONS FROM ALL SICKLE
CELL CENTERS ACROSS THE STATE,
THE SIX COMPREHENSIVE SICKLE
CELL CENTERS AND TWO OTHER SITES
THAT PROVIDE CARE TO PEOPLE WITH
SICKLE CELL DISEASE, AND PEOPLE
WITH LIVED EXPERIENCE.
WE'VE ENGAGED THOSE PARTNERS
THROUGH AN ADVISORY COUNCIL THAT
IS AN INTEGRAL PART OF OUR
PROGRAM AND ADVISES US ON THE
PRIORITIES FOR ANALYSES FOR OUR
STATE.
DR. HULIHAN PRESENTED SOME OF
THE DATA SOURCES, WHAT WE HAVE
CURATED IN NORTH CAROLINA ARE
THE ALL STATE, ALL PAYER ED AND
HOSPITAL DISTAR DISCHARGE DATA M
2013, WE HAVE DUKE HEALTH
ELECTRONIC HEALTH RECORDS,
NEWBORN SCREENING AND VITAL
RECORDS, AND WE ARE -- WE'VE
BEEN WORKING WITH NORTH CAROLINA
MEDICAID AND EXPECT TO RECEIVE
MEDICAID DATA ANY TIME SOON.
SO MY PURPOSES TODAY ARE TO -- I
HAVE -- ARE TWOFOLD.
SO FIRST I'LL TRY AND ILLUSTRATE
HOW WE'RE USING SURVEILLANCE
DATA TO DESCRIBE HEALTHCARE
UTILIZATION IN SICKLE CELL
DISEASE IN NORTH CAROLINA,
FOCUSED ON ED AND HOSPITAL
ADMISSIONS, AND NEXT I'LL
ILLUSTRATE HOW WE'RE USING SOME
OF OUR DATA TO SUPPORT
INITIATIVES ACROSS THE STATES TO
IMPROVE -- ACROSS THE STATE TO
IMPROVE SICKLE CELL CARE.
AS I MENTIONED, THE ANALYSIS I
WILL PRESENT WILL BE FROM ALL
STATE, ALL PAYER ED AND
DISCHARGE DATASET TO IDENTIFY
OUR COHORTS WE USED DATA FROM
2013 TO 2019.
THIS IS A LIMITED PHI DATASET,
SO WE'VE LINKED INDIVIDUALS
USING THEIR DATE OF BIRTH, ZIP
CODE AND SEX ACROSS THE DATA AND
ACROSS THE DIFFERENT TIERS.
WE'VE INCLUDED THE LEVEL 2 CASE
DEFINITION, WHICH IS MORE THAN
AT LEAST THREE ICD CODES FOR
SICKLE CELL DISEASE IN A
FIVE-YEAR PERIOD.
THE PEOPLE HAD TO HAVE -- EITHER
HAVE A VISIT IN 2017 OR HAVE HAD
ANY VISIT BEFORE AND AFTER TO BE
INCLUDED IN THE COHORT.
THE REASONING FOR THAT IS THAT
WE WANTED TO MAKE SURE THEY'RE
STILL IN NORTH CAROLINA.
AND THEY ARE NORTH CAROLINA
RESIDENTS BASED ON THEIR
RESIDENTIAL ZIP CODE.
BY DEFINITION, A HOSPITAL
ADMISSION WHEN I REPORT ON THAT
ENCOMPASSES ALL HOSPITAL
ADMISSIONS THAT IS DIRECT
ADMISSIONS OR ADMISSIONS THAT
STARTED IN THE ED.
ED VISITS ARE ED TREAT AND
RELEASE, MEANING THAT THEY DO
NOT INCLUDE ED TO INPATIENT
ADMISSIONS.
AND WHEN WE REPORT ON AGE, WE'RE
REPORTING ON AGE IN 2017 BECAUSE
WE'RE REPORTING ON UTILIZATION
IN 2017.
SO OUR COHORT FOR THIS ANALYSIS
INCLUDED 5,092 PEOPLE, 54% WERE
FEMALE, 94% AFRICAN AMERICAN,
AND 2% HISPANIC.
THE MEAN MEDIAN AGE IS 25 YEARS
AND ON THE RIGHT SIDE OF THE
SCREEN, YOU CAN SEE THE AGE
DISTRIBUTION WHICH IS WHAT WE
WOULD EXPECT OF THE LIFE
EXPECTANCY OF SICKLE CELL
DISEASE.
ABOUT 13% ONLY OF OUR COHORT WAS
AGED OVER 50 YEARS.
THE TREND THAT YOU SEE HERE IS
SIMILAR TO THE TREND THAT IS
REPORTED BY OTHER STATES,
INCLUDING GEORGIA AND
CALIFORNIA.
SO IT LOOKS LIKE THIS IS AGE
DISTRIBUTION AS SIMILAR TO THE
OTHER STATES.
OF THOSE 5,000 PEOPLE, ABOUT 39%
HAD A HOSPITAL ADMISSION IN
2017.
MEDIAN OF TWO ADMISSIONS AND
LENGTH OF STAY OF SEVEN DAYS.
AND ABOUT 52% HAD AN ED TREAT
AND RELEASE VISIT IN 2017 WITH A
MEDIAN OF TWO VISITS IN THAT
YEAR.
THIS MAP IS SHOWING WHERE THE
5,000 PEOPLE WILL ACROSS THE
STATE.
NORTH CAROLINA HAS ABOUT 100
COUNTIES, AND IT LOOKS LIKE A
MAJORITY OF THE PEOPLE, ABOUT
53%, LIVE IN SIX COUNTIES IN THE
STATE.
OF COURSE THE DARKER THE RED,
THE MORE PEOPLE LIVE IN THOSE --
THE MORE PEOPLE LIVE IN THAT
AREA, AND THEN THE OTHER THING I
WANT TO POINT OUT IS THE
LOCATION OF THE DIFFERENT SICKLE
CELL CENTERS.
THE BLUE ICONS REFER TO THE
DEPARTMENT OF PUBLIC HEALTH
CONTRACTED COMPREHENSIVE SICKLE
CELL CENTERS AND THE TWO GREY
ICONS REFER TO THE OTHER TWO
SICKLE CELL CLINICAL SITES THAT
ARE NOT CONTRACTED BY THE
DEPARTMENT OF PUBLIC HEALTH, BUT
PROVIDE SERVICES TO PEOPLE WITH
SICKLE CELL DISEASE IN THE
STATE.
THE FIRST THING THAT YOU CAN SEE
IN THIS GRAPH IS AN AGGREGATION
OF PEOPLE KIND OF IN THE CENTRAL
AREA OF NORTH CAROLINA WITH FOUR
CENTERS SERVICING ABOUT FIVE
DIFFERENT COUNTIES WITH THE
HIGHEST NUMBER OF PEOPLE WITH
SICKLE CELL DISEASE IN THE
STATE.
THE NUMBER ONE COUNTY THAT HAD
THE HIGHEST NUMBER OF PEOPLE
WITH SICKLE CELL DISEASE IN THE
STATE IS MECKLENBURG COUNTY,
WHICH IS IN THE CHARLOTTE AREA,
AND THERE ARE TWO CENTERS THERE
THAT PROVIDE CARE FOR PEOPLE
WITH SICKLE CELL DISEASE.
CUMBERLAND IS A COUNTY THAT IS
KIND OF -- YOU CAN SEE ABOUT 32O
CENTER CLOSE TO THAT.
THE EASTERN PART OF THE STATE,
THERE'S ONE CENTER IN GREENVILLE
THAT SERVICES THAT PART OF THE
STATE, AND THE WESTERN PART OF
THE STATE, THERE'S ONE CENTER IN
ASHEVILLE, AND THAT'S A
PEDIATRIC CENTER.
SO IT SEEMS THAT WHAT IT LOOKS
LIKE FROM THIS GRAPH IS THAT
MOST PEOPLE WITH SICKLE CELL
DISEASE IN THE STATE HAVE LIVED
OR AGGREGATED AROUND SICKLE CELL
CENTERS.
THERE IS SOME DECREASED ACCESS
POTENTIALLY IN THE WESTERN PART
OF THE STATE AND THE EASTERN
PART OF THE STATE.
OUR PLANS MOVING FORWARD IS TO
LOOK AT THE UTILIZATION OF THESE
PEOPLE, LOOK AT THE TRAVEL TIME
THAT THEY HAVE TO GET SERVICES,
WHETHER OR NOT THEY'RE USING
MULTIPLE SITES FOR THEIR CARE,
AND LOOK AT THE UTILIZATION BY
DISTANCE TO TRY AND UNDERSTAND
BETTER ACCESS TO CARE IN OUR
STATE.
THIS SLIDE IS SHOWING THE NUMBER
OF VISITS BY AGE GROUP AND WE'RE
SHOWING BOTH HOSPITAL ADMISSIONS
AND ED TREAT AND RELEASE VISITS
ON THE SAME SLIDE.
PATIENTS HAD ABOUT -- IN 2017,
THEY HAD ABOUT 5600 TOTAL
HOSPITAL ADMISSIONS.
80% OF THOSE WERE ED TO
INPATIENT ADMISSIONS.
AND THEN THEY HAD ABOUT 9300 ED
TREAT AND RELEASE VISITS.
THE NOT SURPRISING PART OF THE
SLIDE IS, WE SEE UTILIZATION
REALLY JUMP UP BOTH FOR ED AND
HOSPITAL ADMISSIONS BEGINNING AT
AGE 20, SO THE AGE GROUP 20 TO
29 AND AGE GROUP 30 TO 39 HAD
THE HIGHEST UTILIZATIONS BOTH
FOR ED VISITS AND FOR
ADMISSIONS.
AND THEN THAT TAPERS OFF WITH
THE OLDER POPULATION.
THIS IS AGAIN PRELIMINARY DATA
AND WHAT WE'RE WORKING ON RIGHT
NOW WITH OUR ADVISORY COUNCIL IS
AN ANALYSIS THAT LOOKS AT THIS
AGE GROUP SPECIFICALLY, TRYING
TO LOOK AT SOCIAL DRIVERS OF
HEALTH AND USING THE SOCIAL
VULNERABILITY INDEX AND SEE IF
THERE'S ANY PATTERNS THAT WE
COULD IDENTIFY THAT WOULD HELP
US UNDERSTAND BETTER THE REASONS
WHY THOSE ADMISSIONS JUMP
HIGHER.
THIS IS AS REPORTED IN THE
LITERATURE, WE KNOW THIS AGE
GROUP IS THE TIME WHEN PEOPLE
START COMING OFF MEDICAID SO
THEY LOSE INSURANCE.
THEY TRANSITION FROM PEDIATRIC
TO ADULT CARE AND SO THEY LOSE
THEIR CENTERS, AND THAT COULD BE
ONE REASON, BUT WE WANTED TO
SPEND A LITTLE BIT MORE TIME
LOOKING AT SOCIAL DRIVERS OF
HEALTH AS WELL, THAT ANALYSIS IS
NEXT FOR US TO UNDERSTAND THE
UTILIZATION PATTERN FOR THIS AGE
GROUP.
THEN WE LOOKED AT THE PRIMARY
PAYER FOR THOSE VISITS IN 2017.
IN OUR STATES, MEDICAID AND
MEDICARE HAD THE HIGHEST SHARE
OF PAYMENT BOTH FOR ED AND
HOSPITAL ADMISSIONS, ED VISITS
AND HOSPITAL ADMISSIONS PAYING
FOR ALMOST 80% OF THE SERVICES
RENDERED FOR PEOPLE WITH SICKLE
CELL DISEASE IN THE STATE.
WHAT THIS SLIDE IS SHOWING IS
THE PAYIER BY AGE GROUP FOR BOTH
ED VISITS AND HOSPITAL
ADMISSIONS AND AS YOU CAN SEE
MEDICATE STARTS TO TAPER OFF AT
AGE 20 AS PEOPLE COME OFF
MEDICAID AND THEN MEDICARE JUMPS
IN AND COVERS FOR THAT COST AND
A VERY FEW PERCENTAGES IS BEING
COVERED BY OTHER PAYIE PAYERS LE
PRIVATE INSURANCE, SELF PAY AND
OTHER FEDERAL PROGRAMS.
THOSE PATTERNS WERE SIMILAR TO
THE PATTERNS REPORTED BY
CALIFORNIA AND GEORGIA ON THE
TIMING OF WHEN MEDICARE STARTS
COVERING FOR PEOPLE WITH SICKLE
CELL DISEASE AND WHEN MEDICAID
TAPERS OFF SO THE PATTERNS LOOK
SIMILAR TO OTHER STATES.
A COUPLE EXAMPLES ON HOW WE'VE
BEEN PUTTING SOME OF OUR DATA IN
A RELATIVELY NEW PROGRAM, WE'VE
BEEN ESTABLISHED FOR TWO YEARS
AND WE'RE STILL WORKING ON
GETTING OUR DATA TOGETHER, BUT
WE ARE REALLY -- WE PRIDE
OURSELF AS A STATE IN OUR
COLLABORATIONS ACROSS THE AISLE
WITH ALL THE DIFFERENT GROUPS
THAT ARE INVOLVED IN SICKLE CELL
DISEASE ACROSS THE STATE.
AND SO WE ARE INVOLVED IN THE
GOVERNOR'S COUNCIL WHICH HAS A
MEDICAL RESEARCH COMMITTEE.
THE MEDICAL RESEARCH COMMITTEE
IDENTIFIED ED CARE AS A PRIORITY
OF CARE FOR PEOPLE WITH SICKLE
CELL DISEASE IN NORTH CAROLINA,
AND THEY HAVE BEEN WANTING TO
IMPLEMENT A STANDARDIZED PAIN
MANAGEMENT PLAN ACROSS ALL EDs
IN NORTH CAROLINA TO IMPROVE
PAIN MANAGEMENT AND DECREASE
HOSPITAL ADMISSIONS.
THERE'S BEEN A LOT OF WORK
ACROSS OUR STATE FROM DIFFERENT
INVESTIGATORS TO TRY AND IMPROVE
ED CARE ACROSS THE STATE AND
THIS IS KIND OF THE NUMBER ONE
COMPLAINT WE HEAR FROM OUR
PATIENTS WHEN THEY EXPRESS THEIR
SATISFACTION WITH CARE.
SO THE GOVERNOR'S COUNCIL, THE
MEDICAL RESEARCH COMMITTEE TOOK
THIS AS A PRIORITY FOR THIS YEAR
AND WHAT WE'RE DOING TO SUPPORT
THIS INITIATIVE TO HELP THEM
IMPLEMENT THE STANDARDIZED PLANS
IS HELP IDENTIFY THE TOP 20 ED
CENTERS WITH THE HIGHEST NUMBER
OF ED VISITS IN IN ORDER
CAROLINA.
SO WE'RE PROVIDING THEM WITH A
TABLE, THEY HAVE NOT RECEIVED
THIS YET, SO OUR TEAM JUST
FINISHED WORKING ON THIS LAST
WEEK.
WE'RE PROVIDING THEM WITH A LIST
OF THE TOP 20 FACILITIES IN THE
STATE THAT HAVE THE HIGHEST
ADMISSIONS OR THE HIGHEST NUMBER
OF ED VISITS.
THIS WILL HELP THEM TARGET THOSE
FACILITIES AND HELP EDUCATE AND
IMPLEMENT THE ED PAIN MANAGEMENT
PLAN.
THIS IS ONE EXAMPLE.
THE OTHER EXAMPLE IS WE'RE
COLLABORATING WITH THE NORTH
CAROLINA MEDICAID, THE DIVISION
OF HEALTH BENEFITS.
THEY HAVE LAUNCHED AN INITIATIVE
TO IMPROVE ACCESS TO SC TO TCD
SCREENING AND ELIMINATE BARRIERS
TO TCD SCREENING AMONG PEOPLE
WITH SICKLE CELL TO AGE 16 AND
WE'RE WORKING CLOSELY WITH THEM
TO HELP THEM ASSIST IN DEFINING
THE COHORT AND PROPOSING
LINKAGES WITH NEWBORN SCREENING
SO THEY CAN HAVE AN APPROPRIATE
UNDERSTANDING OF THE UTILIZATION
OF TCD SCREENING AND SOME OF THE
BARRIERS THAT ARE HAPPENING.
SO WE'RE SUPPORTING MORE OF --
WE'RE PROVIDING MORE OF A
TECHNICAL SUPPORT TO HELP
UNDERSTAND THE PREVALENCE OF TCD
SCREENING IN THE STATE AND WHAT
COULD BE SOME OF THE BARRIERS.
THE NORTH CARE LAY NORTH CAROLIS
LAUNCHING THIS INITIATIVE TO
HOPEFULLY HAVE MORE ACCESS TO
TCD SCREENING AMONG THE
PEDIATRIC POPULATION IN NORTH
CAROLINA.
ONE OF OUR PROJECTS IS REALLY
FOCUSED ON ACUTE HEALTHCARE
UTILIZATION AND ED VISITS AND
THE OTHER IS FOCUSED ON
PREVENTIVE CARE AND WE FEEL VERY
FORTUNATE TO BE ABLE TO
CONTRIBUTE SOME ASSISTANCE IN
THOSE TWO IMPORTANT AREAS FOR
OUR STATE.
NEX
SO IN SUMMARY, REALLY, THE DATA
IS LIKE ANY OTHER SECONDARY
DATASET WITH A LOT OF MISSING
DATA, POTENTIAL DATA ERRORS AND
DATA ACCURACY AND CHALLENGES AND
LINKAGES BECAUSE THE DIFFERENT
DATA COME WITH DIFFERENT PHI AND
SOME DOES NOT ACTUALLY HAVE PHI
SO WE HAVE A LOT OF CHALLENGES
THERE, BUT THE OPPORTUNITIES ARE
GREAT BECAUSE, ONE, THIS IS --
THESE MULTIPLE DATA SOURCES
REPRESENT -- BETTER REPRESENT
THE POPULATION.
FOR EXAMPLE, WHEN YOU'RE LOOKING
AT ALL STATE, ALL PAYER
UTILIZATION, WE'RE ABLE TO LOOK
AT ALL PAYERS AND ALL THE
UTILIZATION THAT IS HAPPENING
ACROSS THE STATE AND WE'RE NOT
MISSING ANY AREAS.
COMBINING MULTIPLE DATA SOURCES
INCREASES THE COMPREHENSIVENESS
OF THE DATA THAT WE HAVE IN THE
DATASET, SUCH AS NEWBORN
SCREENING, VITAL RECORDS, THE
ABILITY TO COMBINE WITH OTHER
SOCIAL DRIVERS OF HEALTH
DATASETS ALSO.
IT CAN HELP GUIDE INTERVENTIONS
TO IMPROVE CARE AT THE STATE
LEVEL SUCH AS THE EXAMPLES I
HAVE PROVIDED.
IT CAN HELP GUIDE POLICY TO
IMPROVE CARE AT THE STATE LEVEL
AND IT KEEPS -- IT CAN HELP US
ENGAGE OTHER KEY PLAYERS AT THE
STATE LEVEL, SUCH AS THE CBOs
AND THE COUNCILS, THE GOVERNOR'S
COUNCILS AND THE MEDICAL
RESEARCH COMMITTEE THAT I HAVE
MENTIONED.
IN CLOSING, I WOULD LIKE TO
ACKNOWLEDGE OUR TEAM.
THIS IS A BIG TEAM BETWEEN THE
DIVISION OF PUBLIC HEALTH,
BETWEEN DUKE AND PIEDMONT HEALTH
SERVICES, AND WE WORK VERY
COLLABORATIVELY TO PUT THIS
TOGETHER.
I WANT TO ACKNOWLEDGE AND THANK
CDC AND THE OTHER SPHAITS FOR OR
THEIR SUPPORT AND A BIG SHOUT
OUT TO OUR ADVISORY COUNCIL WHO
KEEPS US FOCUSED ON WHAT IS
IMPORTANT IN TERMS OF ANALYSES
FOR OUR STATE AND WHO'S VERY
ENGAGED IN HELPING US DETERMINE
THOSE PRIORITIES.
I WOULD BE -- I THINK THAT'S MY
LAST SLIDE.
I'D BE HAPPY TO ENTERTAIN ANY
QUESTIONS, AND I'VE LEFT MY
EMAIL ADDRESS OVER THERE SO
PLEASE FEEL FREE TO REACH OUT IF
YOU HAVE ANY QUESTIONS.
>> THANK YOU SO MUCH, MARIAM.
AND I DO THINK SEVERAL QUESTIONS
CAME IN THE CHAT AND THE Q & A,
AND WE'LL -- IF YOU WANT TO
ANSWER THOSE OR IF THEY'RE ONES
THAT AREN'T APPROPRIATE FOR YOU
TO ANSWER, MARIAM, WE CAN SAVE
THEM TO THE END AS WELL.
>> I WILL, THANK YOU.
>> THANKS SO MUCH.
OKAY.
SO WE'RE GOING TO MOVE ON AND
NEXT WE HAVE JACKIE VALLE FROM
THE CALIFORNIA SCDC PROGRAM.
JHAQUE IS GOING TO TALK ABOUT
HOW THIS PROGRAM CAN INFLUENCE
ACCESS TO HEALTHCARE
UTILIZATION.
AS WE MENTIONED AT THE
BEGINNING, IT'S GREAT TO COLLECT
ALL THIS DATA BUT REALLY WHAT
WE'RE TRYING TO DO IS USE TO
MAKE A DIFFERENCE TO IMPROVE
PEOPLE'S LIVES.
ONE WAY THAT THIS IS VERY
VALUABLE IS INCREASING ACCESS TO
CARE.
SO WITH THAT, JHAQUE, I WILL
TURN IT OVER TO YOU.
>> THANK YOU, EVERYONE.
AS MARY MENTIONED, I'M WITH THE
CALIFORNIA DATA COLLECTION
PROGRAM AND I'M GOING TO BE
TALKING ABOUT ACCESS TO
HEALTHCARE.
AS YOU'VE ALREADY HEARD FROM
SEVERAL OTHER STATES ABOUT THE
SICKLE CELL DATA COLLECTION
PROGRAM I WON'T GO INTO TOO MUCH
DETAIL BUT QUICKLY NOTING THE
CALIFORNIA PROGRAM HAS BEEN
AROUND FOR AROUND 10 YEARS WHEN
YOU INCLUDE THE PILOT PROGRAMS
OF THIS SURVEILLANCE SYSTEM SO
WE'VE HAD TIME TO TEST AND
VALIDATE OUR SYSTEM, PROCESSING
LINKAGE PROGRAMS A COUPLE TIMES
OVER.
BEFORE I GET INTO THE ANALYSIS,
FOR SOME CONTEXT IN TERMS OF THE
NUMBER OF PEOPLE WITH SICKLE
CELL DISEASE THAT WE ESTIMATE TO
BE IN CALIFORNIA, THERE'S TWO
COLUMNS HERE.
THE ONE ON THE LEFT, THE PEOPLE
WE HAVE THE MOST INFORMATION ON,
7,000, WE KNOW THEY WERE IN THE
STATE DURING THIS TIME PERIOD.
THE OTHER COLUMN INCLUDES PEOPLE
THAT WE KNOW ARE IN THE STATE AT
SOME POINT BUT CAN'T -- IT COULD
BE -- THEY HAVE PRIVATE
INSURANCE AND ARE NOT SEEKING
CARE OR MAYBE THEY MOVED -- TO
GIVE YOU A SENSE OF WHERE WE'RE
AT ON THAT.
SO THE GOAL OF THE PROGRAM IS
REALLY TO USE THE DATA TO
IMPROVE CARE OUTCOMES AND
QUALITY OF LIFE FOR THOSE WITH
SICKLE CELL DISEASE.
AND SO USING OUR DATA, WE WANTED
TO EXAMINE INDIVIDUALS WITH
SICKLE CELL DISEASE ACCESS TO
SPECIALTY CARE.
AS WE KNOW THIS POPULATION HAS
HISTORICALLY ENCOUNTERED
SIGNIFICANT SYSTEMIC AND
INSTITUTIONAL BARRIERS IN ACCESS
TO CARE.
SICKLE CELL DISEASE IS COMPLEX,
IT REQUIRES COORDINATION BETWEEN
PRIMARY SPECIALTY CARE INCLUDING
HEMATOLOGISTS TO REALLY PREVENT
COMPLICATIONS THAT REDUCE
QUALITY OF LIFE.
SO WITH THIS QUESTION OF ACCESS
TO CARE IN MIND WE WANTED TO
REFINE THAT A LITTLE BIT MORE TO
HOW MANY MEDICAID PATIENTS WITH
SICKLE CELL DISEASE SEE A
HEMATOLOGIST.
JUST TO NOTE, NOT ALL
HEMATOLOGISTS ARE EXPERTS IN
TREATING SICKLE CELL DISEASE AND
WE ALSO KNOW THERE CAN BE
PRIMARY CARE PROVIDERS THAT CAN
BE VERY KNOWLEDGEABLE AND
EXPERIENCED IN TREATING PATIENTS
WITH SICKLE CELL DISEASE SO THIS
IS REALLY LOOKING AT THIS ISSUE
ATITY MOST BASIC LEVEL.
AT ITS MOST BASIC LEVEL.
SO THE CALIFORNIA AND GEORGIA
TEAM LED THIS RETROSPECTIVE
COHORT ANALYSIS USING CALIFORNIA
AND GEORGIA DATA.
INCLUSION CRITERIA WERE
INDIVIDUALS WITH SICKLE CELL
DISEASE WITH THREE CONTINUOUS
MEDICAID COVERAGE, WITH NO
BREAKS IN COVERAGE WHEN WE WERE
TRYING TO DETERMINE WHETHER OR
NOT THEY SOUGHT CARE.
WE USED MEDICAID ENROLLMENT DATA
WHICH INCLUDES MONTHLY
INFORMATION ON COVERAGE, CLAIMS
DATA WHICH INCLUDES ALL CLAIMS
FOR INPATIENT, OUTPATIENT,
PHARMACY CLAIMS, ET CETERA.
AS WELL AS PROVIDER NPI NUMBERS.
WE THEN LINKED EACH CLAIM TO THE
NPI DATABASE TO OBTAIN THE
PROVIDER SPECIALTY IN ORDER TO
IDENTIFY THE HEMATOLOGIST AND
FOR EACH PERSON WE CALCULATED
THE TOTAL NUMBER OF HEMATOLOGIST
ENCOUNTERS WITHIN THE 2016 TO
2018 TIME PERIOD.
A COUPLE QUICK RESULTS.
THIS IS PEDIATRIC POPULATION,
YOU CAN SEE THE PROPORTION OF
PEDIATRIC PATIENTS IN OUR DATA
WHO HAD NO ENCOUNTERS WITH A
HEMATOLOGIST IN ANY OF THOSE
GIVEN YEARS WITHIN THAT
THREE-YEAR PERIOD, AROUND 30% IN
CALIFORNIA AND 20% IN GEORGIA.
AMONG THE ADULTS, THE PICTURE IS
NOT AS GREAT AS ALL.
YOU CAN SEE THE PROPORTION WITH
ZERO ENCOUNTERS IN ONE YEAR WAS
BETWEEN 63 AND 68% IN
CALIFORNIA.
SLIGHTLY BETTER BE NUMBERS IN
GEORGIA WITH 48 TO 49% HAVING AN
ENCOUNTER WITH A HEMATOLOGIST.
THOSE NUMBERS DID IMPROVE A
LITTLE BIT WHEN YOU LOOK AT THE
FULL THREE YEARS.
CALIFORNIA CROPP DROPPED DOWN T%
AND GEORGIA DOWN TO 34%.
SO WHEN WE WERE LOOKING AT THIS,
WE EXPECTED THERE WOULD BE SOME
CONCERN IN TERMS OF WHETHER OR
NOT THEY WERE SEEING ANY
HEMATOLOGISTS BUT THESE NUMBERS
WERE A LOT HIGHER THAN EXPECTED
IN TERMS OF THE PROPORTION OF
PERSONS WHO DIDN'T SEE A
HEMATOLOGIST ESPECIALLY AMONG
THE PEDIATRIC PATIENTS, ABOUT A
THIRD FOR CALIFORNIA AND A
QUARTER FOR GEORGIA WHO HAD NOT
SEEN A HEMATOLOGIST IN A YEAR.
SO THIS HIGHLIGHTS AN
OPPORTUNITY TO IMPROVE ACCESS TO
SPECIALTY CARE FOR PATIENTS WITH
SICKLE CELL DISEASE AND THE NEXT
SLIDE, WE WANT TO SHOW YOU AN
EXAMPLE OF HOW WE TAKE SOMETHING
LIKE THIS AND MAKE IT A LITTLE
BIT MORE TARGETED FOR OUR
POPULATION IN CALIFORNIA.
SO OUR FOLLOW-UP QUESTION TO
THIS WAS WHERE ARE EXPERIENCED
PROVIDERS LOCATED AND WHERE DO
PEOPLE WITH SICKLE CELL DISEASE
LIVE?
SO IN THIS, WE WANT TO TAKE A
CLOSER LOOK TO LOS ANGELES
COUNTY.
THEY HAVE APPROXIMATELY
9 MILLION PEOPLE WITH I IS ABOUT
A THIRD OF THE CALIFORNIA
POPULATION.
37% OF CALIFORNIANS LIVING WITH
SICKLE CELL DISEASE IN
LOS ANGELES COUNTY, SO THE
LARGEST AMONG ALL COUNTIES IN
CALIFORNIA.
LA COUNTY IS DIVIDED INTO EIGHT
SERVICE PLANNING AREAS TO KIND
OF DEVELOP AND PROVIDE TARGETED
PUBLIC HEALTH IN CLINICAL
SERVICES.
WE FOCUSED ON THIS SERVICE
PLANNING AREA SPA6, WHICH IS THE
SOUTH ONE.
BASICALLY IT HAS THE LARGEST
NUMBER OF INDIVIDUALS LIVING
WITH SICKLE CELL DISEASE IN LA
COUNTY AND HIGHEST AREA OF
SOCIAL VULNERABILITY.
THIS INDEX IDENTIFIES VULNERABLE
NEIGHBORHOODS BASED ON A VARIETY
OF FACTORS LIKE POVERTY,
UNEMPLOYMENT, HOUSING,
TRANSPORTATION ACCESS.
IT KIND OF DEPO GOES ON FROM TH.
THE INCLUSION CRITERIA WAS
SIMILAR TO THE PREVIOUS
ANALYSIS, PATIENTS HAVING HAD --
DATA SOURCES REMAIN THE SAME BUT
WE ALSO INCLUDED EXPERIENCED
PROVIDERS AND EXPERIENCED
PROVIDER WAS EITHER HEMATOLOGIST
OR PRIMARY CARE PROVIDER THAT
SAW AT LEAST 20-PLUS MEDICAID
PATIENTS LIVING WITH SICKLE CELL
DISEASE IN THAT THREE-YEAR
PERIOD.
AND FROM THERE, WE WERE ABLE TO
IDENTIFY INDIVIDUALS IN SPA
6 WHO DID NOT SEE AN EXPERIENCED
PROVIDER.
SO THE GOAL OF THIS ANALYSIS
WHICH WE'RE STILL KIND OF
REFINING IN TERMS OF OUR
MATERIALS IS REALLY TO BE ABLE
TO PROVIDE -- WE CAN MAKE IT A
LITTLE BIT MORE ACCESSIBLE TO
OUR STAKEHOLDERS, NGOs AND
OTHER PARTNERS SO WE WANTED TO
BE ABLE TO VISUALLY SEE WHERE
THE EXPERIENCED PROVIDERS WERE
LOCATED IN COMPARISON TO THE
PATIENTS.
THE HIGHLIGHTED SHADED AREAS ARE
ALL THE ZIP CODES WITHIN SPA6.
IT GOES IN LIGHT TO DARK BASED
ON PROPORTION OF PATIENTS WITH
ENCOUNTERS WITH THE DARKEST ZIP
CODES HAVING THREE QUARTERS OF
THE PATIENTS WITH ZERO
ENCOUNTERS.
AS YOU CAN SEE, THE MAJORITY OF
EXPERIENCED PROVIDERS ARE
LOCATED OUTSIDE OF SPA6.
SO KIND OF IN CONCLUSION, WE
KNOW THAT SICKLE CELL DISEASE
LIKE ANY BLOOD DISORDER REQUIRES
SPECIALIZED EXPERTISE.
THOSE NOT SEEN BY HEMATOLOGISTS
IS ALARMINGLY HIGH EVEN AMONG
PEDIATRIC PATIENTS WHO ARE OFTEN
THOUGHT TO HAVE BETTER CARE,
BETTER ACCESS TO COMPREHENSIVE
CARE CENTERS, OVER HALF WERE
STILL NOT SEEN BY HEMATOLOGISTS
OR EXPERIENCED PRIMARY CARE
PHYSICIAN.
THIS WILL HIGHLIGHTS AN
OPPORTUNITY TO IMPROVE ACCESS TO
CARE FOR SICKLE CELL DISEASE
PATIENTS ENROLLED IN MEDICAID,
TO START DISCUSSION WITH POLICY
MAKERS AND OTHERS DUE TO
POSSIBLE BARRIERS TO CARE.
I THINK THAT'S THE LAST SLIDE I
HAVE.
THANKS TO ALL THE ADVISORY
BOARDS AND THOSE THAT HAVE
WORKED WITH US AND I THINK
THAT'S IT.
I'LL BE HAPPY TO ANSWER
QUESTIONS.
>> THANK YOU SO MUCH, JHAQUE.
AND THANKS TO EVERYONE FOR THE
WONDERFUL QUESTIONS THAT ARE
COMING IN THROUGH THE Q & A AND
THE CHAT.
WE'LL EITHER ANSWER THOSE ONLINE
OR GET TO THEM AT THE END FOR
SURE.
SO MOVING ON TO OUR NEXT
PRESENTATION, WE ARE LUCKY TO
HAVE TWO TEAM MEMBERS FROM THE
MICHIGAN SCDC TEAM.
DOM SMITH AND SARAH REEVES ARE
GOING TO BE CO-PRESENTING THE
NEXT INFORMATION.
AND THEY ARE GOING TO SHOW SOME
RECENT WORK THAT'S GOING ON IN
MICHIGAN, AND IT'S LOOKING AT
WAYS TO USE THIS DATA TO WORK
WITH HEALTHCARE POLICY AND
HEALTHCARE POLICY MAKERS TO
IMPROVE THE LIVES OF PEOPLE WITH
SICKLE CELL DISEASE.
SO THE PROJECT IS SPECIFIC TO
MICHIGAN, BUT I THINK ALL OF US
WHO ARE LISTENING ON THE PHONE
CAN IMAGINE THAT IT COULD
CERTAINLY BE EXTRAPOLATED TO
OTHER STATES THROUGHOUT THE U.S.
SO I WILL TURN IT OVER TO THE
MICHIGAN TEAM.
THANK YOU SO MUCH.
>> THANK YOU, MARY.
AND I WILL KICK US OFF.
SOL YOU'VE HEARD ABOUT HOW A LOT
OF THE STATES HAVE BEEN ABLE TO
ACCOMPLISH THIS WORK THROUGH A
GRANT OF PUBLIC HEALTH AUTHORITY
AND THAT'S EXACTLY WHAT WE'VE
BEEN ABLE TO ESTABLISH HERE IN
MICHIGAN THROUGH OUR PARTNERSHIP
WITH THE MICHIGAN DEPARTMENT OF
HEALTH AND HUMAN SERVICES AND
UNIVERSITY OF MICHIGAN.
AND OUR SCDC PROGRAM IS LED BY
DR. SARAH REEVES.
AND I'LL TALK ABOUT HOW WE'VE
BEEN ABLE TO IMPLEMENT THIS NEW
POLICY INITIATIVE UTILIZING OUR
CHILDREN'S SPECIALTY HEALTHCARE
SERVICES PROGRAM AND THE
SURVEILLANCE SYSTEM.
SO A KEY MESSAGE THAT WE WANTED
TO SHARE THAT YOU'VE HEARD
OTHERS EXPRESS AS WELL IS
UNDERSTANDING THE TRUE NUMBER OF
PEOPLE WITH SICKLE CELL DISEASE
IN A STATE, AS WELL AS WHERE
THEY LIVE, ARE ESSENTIAL
CONSIDERATIONS WHEN EXPANDING
POLICIES AND SERVICES FOR PEOPLE
WITH SICKLE CELL DISEASE.
AND IF THESE TWO THINGS AREN'T
ACCURATELY DETERMINED, THEN
THESE POLICIES THAT ARE
IMPLEMENTED MAY FALL SHORT OF
THEIR TRUE POTENTIAL.
SO AS WE START TO TALK ABOUT
THIS PARTICULAR CASE STUDY, I
WANTED TO GIVE JUST A LITTLE BIT
OF BACKGROUND ABOUT HOW WE GOT
HERE.
SO IN MICHIGAN, OUR CHILDREN
SPECIAL HEALTHCARE SERVICES
PROGRAM SERVES APPROXIMATELY
60,000 CHILDREN WITH SPECIAL
NEEDS, AND IT COVERS ABOUT 2700
DIFFERENT DIAGNOSES.
AND LONG TERM COVERAGE HAS ONLY
BEEN AVAILABLE FOR CHILDREN UP
TO THE AGE OF 21, BUT FOR 2
SPECIFIC CONDITIONS, CYSTIC
FIBROSIS AND HEMOPHILIA,
COVERAGE -- THIS EXPANDED
COVERAGE INCLUDES SERVICES FOR
MEDICAL CARE AND TREATMENT, CARE
COORDINATION, TRANSPORTATION,
MEDICAL HOMES AND ADDITIONAL
SUPPORT SERVICES.
AND THIS PROGRAM IS FUNDED BY
TITLE 5-DOLLARS, GENERAL FUND
DOLLARS AS WELL AS MEDICAID.
BUT FOR THE PAST COUPLE YEARS,
THERE HAVE BEEN ONGOING
CONVERSATIONS IN OUR STATE ON
HOW WE COULD EXPAND THESE
BENEFITS FOR THE SICKLE CELL
DISEASE POPULATION OVER THE AGE
OF 21 ACROSS THE LIFESPAN.
IN MICHIGAN, WE WERE
SUCCESSFULLY ABLE TO DO THAT
BEGINNING IN FQ22 BY CHANGING
OUR PUBLIC HEALTH CODE AND
ADDING SOME ADDITIONAL DOLLARS
FOR OTHER THINGS IN OUR STATE
WHICH I'M ABOUT TO TELL YOU
ABOUT.
SO EACH YEAR, WE HAVE
OPPORTUNITIES TO PRESENT TO OUR
GOVERNOR AND OUR STATE
LEGISLATURE WHAT WE CALL IN OUR
STATE PROPOSALS FOR CHANGE, AND
THEY'RE REALLY TRANSFORMATIONAL,
THEY'RE MEANT TO BE BIG IN SCOPE
AND TRANSFORMATIONAL
OPPORTUNITIES AND ONLY A FEW
ACTUALLY END UP MAKING IT
THROUGH OUR STATE LEGISLATURE
AND TO OUR GOVERNOR TO SIGN INTO
LAW.
AND THE THINGS WE WERE ABLE TO
DO IN RECEIVING A $6.7 MILLION
BUDGET TO DO IT WAS EXPANDING
CHILDREN SPECIAL HEALTHCARE
SERVICES FOR SICKLE CELL DISEASE
FOR INDIVIDUALS OVER THE AGE OF
21.
WE WERE ABLE TO INCLUDE DOLLARS
FOR OUR STATE COMMUNITY-BASED
ORGANIZATION, THE SICKLE CELL
DISEASE ASSOCIATION OF MICHIGAN,
AND WE WERE ALSO ABLE TO INCLUDE
GRANT DOLLARS TO SUPPORT SICKLE
CELL CLINICS IN OUR STATE.
AND WE INCLUDE A COMPONENT IN
THAT PROPOSAL FOR CHANGE, WE
BUILT IN THE SICKLE CELL
SURVEILLANCE SYSTEM, AND HOW WE
WOULD USE SCDC DATA ALONG THE
WAY TO EVALUATE THIS PROCESS OR
TO INFORM OUR ACTIVITIES,
PROJECTS AND POLICIES ALONG THE
WAY.
AND THAT LED TO WHAT YOU'RE
GOING TO HEAR ABOUT TODAY, THE
UNIVERSITY OF MICHIGAN POLICY
AND THE CASE STUDY THEY'RE GOING
TO TALK MORE ABOUT.
AND I JUST WANT TO ALSO SHARE
THAT I'M HAPPY TO REPORT ALSO IN
MICHIGAN, FOR THIS FISCAL YEAR
FOR THE 23 UPCOMING BUDGET, WE
WERE ABLE TO GET ANOTHER
$2.5 MILLION TO DEVELOP A SICKLE
CELL CENTER OF EXCELLENCE IN THE
CITY OF DETROIT, AND WE HAVE
ALSO BEEN ABLE TO MAXIMIZE THE
INITIAL SET OF MONEY THAT WE GOT
THROUGH MEDICAID MATCH, AND WE
ARE GOING TO BE ABLE TO EXPAND
THOSE CLINICAL GRANTS THAT WE
WERE -- WE FUNDED THREE GRANTS
INITIALLY, BUT WE'RE ABLE TO
MAXIMIZE OUR DOLLARS AND OUR
PLAN IS TO FUND MORE CLINICS IN
FY 23.
SO I WILL TURN IT OVER TO SARAH,
AND SHE IS GOING TO TELL YOU
ABOUT HOW WE'RE LEVERAGING THE
SICKLE CELL DISEASE SURVEILLANCE
SYSTEM TO MAXIMIZE ADULT
ENROLLMENT FOR CSHCS.
THANK YOU.
>> THANKS, DOM.
SO AS DOM MENTIONED, IT'S
AMAZING THAT THEY WERE ABLE TO
LEVERAGE THEIR RESOURCES AND
EXPAND THE PUBLIC HEALTH CODE TO
INCLUDE PEOPLE WITH SICKLE CELL
DISEASE AND CSHCS OVER THE AGE
OF 21, BUT WE NEED TO ENROLL
THEM.
SO TO BE ABLE TO ENROLL ADULTS
IN THESE NEWLY EXPANDED
BENEFITS, THE STATE NEEDS TO BE
ABLE TO KNOW WHO IS LIVING WITH
SCDC IN OUR STATE AND ALSO KNOW
HOW TO CONNECT WITH THOSE FOLKS
TO BE ABLE TO REACH OUT TO THEM
TO ENROLL THEM IN THE EXPANDED
BENEFITS.
THERE WERE A LOT OF WAYS THAT WE
COULD THINK ABOUT REACHING
ADULTS WITH SICKLE CELL DISEASE
AND ONE WAS THINKING ABOUT
REACHING OUT TO PEOPLE THAT HAD
PREVIOUSLY AND RECENTLY BEEN
ENROLLED IN CSHCS, SO MAYBE
PEOPLE AGES 21 TO 26-ISH THAT
HAD BEEN ENROLLED PREVIOUSLY BUT
HAD AGED OUT GIVEN THE AGE CAP
THAT HAD PREVIOUSLY BEEN IN
PLACE.
AND SO THAT WAS ABOUT 400
ADULTS.
SO IF WE WENT WITH THAT RECENT
CSHCS ENROLLMENT IN TERMS OF
OUTREACH TO ADULTS WITH SICKLE
CELL DISEASE, THERE WERE ONLY
ABOUT 400 ADULTS THAT WERE
ELIGIBLE.
BUT THERE'S OBVIOUSLY MORE
PEOPLE LIVING IN THE STATE THAT
ARE OVER THE AGE OF 21 WITH
SICKLE CELL DISEASE.
WE CAN THINK OF A LOT OF
DIFFERENT GROUPS, PEOPLE THAT
MOVED TO MICHIGAN AS AN ADULT SO
WERE NOT IN CSHCS PREVIOUSLY,
OLDER POPULATIONS, PEOPLE OVER
THE AGE OF, SAY, 26, 30, 40, AND
PEOPLE THAT WERE NEVER ENROLLED
SO EVEN A 21-YEAR-OLD OR
22-YEAR-OLD THAT HAD NEVER BEEN
ENROLLED IN CSHCS, THOSE GROUPS
OF INDIVIDUALS WITH SICKLE CELL
DISEASE WOULD NOT BE INCLUDED
WHEN WE WERE JUST DOING OUTREACH
TO THOSE THAT HAD HAD RECENT
CSHCS ENROLLMENT.
SO THE MICHIGAN SCDC MISCDC
PARTNERSHIP, TO ENHANCE OUTREACH
TO INDIVIDUALS WITH SICKLE CELL
DISEASE THAT WERE ELIGIBLE FOR
THESE NEWLY EXPANDED BENEFITS.
THIS WAS FUNDED AT THE
UNIVERSITY OF MICHIGAN AND OUR
TWO OVERALL GOALS WERE TO
IDENTIFY AND CHARACTERIZE
INDIVIDUALS THAT WERE ELIGIBLE
FOR EXPANDED BENEFITS, AND THEN
ASSIST MDHHS ENSURING THEY HAD
THE MOST RECENT INFORMATION
AVAILABLE TO CONNECT WITH PEOPLE
FOR OUTREACH MATERIALS TO HELP
ENROLL THEM IN EXPANDED
BENEFITS.
NUMEROUS PEOPLE ON THE CALL HAVE
EXPLAINED THE DATA SOURCES THAT
GO INTO SCDC, SO WE USED THE
COMBINATION OF ALL THOSE DATA
SOURCES TO IDENTIFY PEOPLE THAT
HAD SICKLE CELL DISEASE AND HAD
BEEN IN THE STATE AT SOME POINT
BETWEEN 2016 AND 2022.
AND ALSO WERE ALIVE AND OVER 20
YEARS OLD AT THE TIME OF CHSCS
EXPANSION.
AFTER WE IDENTIFIED PEOPLE THAT
WERE ELIGIBLE FOR EXPANDED
BENEFITS USING THIS MULTISOURCE
DATA, AND AGAIN THIS IS SO
IMPORTANT BECAUSE IT'S
IRRESPECTIVE OF INSURANCE STATUS
OR AGE, WE WORKED WITH MDHHS
DATA TO ESTABLISH CONNECTION
FORGS OUTREACH.
WHEN WE LEVERAGED THE SCDC DATA,
IF YOU REMEMBER WHEN WE WERE
JUST THINKING ABOUT REACHING OUT
TO PEOPLE WITH RECENT CSHCS
ENROLLMENT -- HOWEVER WHEN WE
COMBINED ALL THE DATA WE
IDENTIFIED AN ADDITIONAL 2,169
PEOPLE FOR A TOTAL OF JUST OVER
2500 ADULTS LIVING IN THE STATE
THAT WERE ELIGIBLE TO BE
ENROLLED IN THESE EXPANDED CSHCS
BENEFITS.
WE IDENTIFIED CONTACT
INFORMATION FOR 99.4% OF THOSE
ELIGIBLE PEOPLE OF THE 2500
PEOPLE.
AND FOR THE PEOPLE WE IDENTIFIED
CONTACT INFORMATION FOR, 80.4%
HAD INFORMATION THAT HAD BEEN
UPDATED AS RECENTLY AS 2022.
WE LOOKED AT A LOT OF DIFFERENT
DATA SOURCES FOR THIS.
WE LOOKED AT THE IMMUNIZATION
REGISTRY, WE LOOKED AT CLINIC
DATA TO UNDERSTAND THE ADDRESSES
AND OTHER THINGS, WE LOOKED AT
MEDICAID.
SO WHEN WE COMBINED ALL OF THOSE
SOURCES AND PICKED THE MOST
RECENT AND RELIABLE DATA, IT WAS
OVER 80% OF FOLKS HAD VERY
RECENT CONTACT INFORMATION.
SO WHAT WE WANTED TO EMPHASIZE
WITH THIS WAS THAT WHEN WE WERE
ABLE TO USE THE POPULATION-BASED
DATA, WE IDENTIFIED AN
ADDITIONAL 2100 PEOPLE WITH
SICKLE CELL DISEASE THAT WERE
ELIGIBLE FOR EXPANDED BENEFITS
BEYOND JUST RELYING ON RECENT
CSHCS ENROLLMENT.
IDENTIFYING MORE RECENT CONTACT
INFORMATION IS GOING TO ALLOW AN
ADDITIONAL LAYER OF CONNECTION
AND OUTREACH TO ADULTS IN TERMS
OF MAILINGS, COORDINATION WITH
LOCAL HEALTH DEPARTMENTS, AND
THIS IS TRUE PARTICULARLY FOR
ADULTS.
I THINK YOU'VE SEEN THROUGH THE
DATA THAT MULTIPLE STATES HAVE
ALREADY PRESENTED THAT ADULTS
CAN BE A TRICKIER POPULATION TO
CONNECT WITH, GIVEN THE FACT
THAT THE PATTERNS OF HEALTHCARE
UTILIZATION.
SO THIS IS AN IMPORTANT STEP
FORWARD FOR REACHING ADULTS WITH
SICKLE CELL DISEASE IN OUR
STATE.
AND THEN FINALLY, WITH SCDC IN
PLACE, OTHER STATES COULD USE
THIS METHODOLOGY TO BE ABLE TO
IDENTIFY MORE INDIVIDUALS WITH
SICKLE CELL DISEASE TO BE
CONNECTED WITH RESOURCES AND
IMPACTED BY NEW POLICIES.
AGAIN, KNOWING THE FULL
POPULATION OF PEOPLE WITH SICKLE
CELL DISEASE AND WHERE THEY LIVE
IS REALLY IMPORTANT WHEN
THINKING ABOUT THESE POLICIES,
OR ELSE THEY WILL NOT REACH
THEIR FULL POTENTIAL.
THIS IS JUST ONE CASE EXAMPLE OF
HOW WE CAN USE POPULATION-BASED
DATA AND COLLABORATIONS ACROSS
THE STATE.
THERE'S PLENTY OF ADDITIONAL
SCDC POLICY CONTRIBUTIONS.
THESE ARE JUST -- IT WAS ALMOST
OVERWHELMING TO TRY TO PUT THIS
IN A COUPLE SLIDES.
THE AMAZING WORK THAT'S BEEN
DONE IN THE LAST DECADE OR SO.
SSCDC PROVIDES DATA TO A WIDE
VARIETY OF ORGANIZATIONS.
ALL OF US HAVE EXPERIENCED THESE
REQUESTS TO STATE HEALTH
DEPARTMENT THS, LEGISLATORS,
NON-PRO FIPROFIT ORGANIZATIONS,
COMMUNITY-BASED ORGANIZATIONS.
I'M GOING TO PROVIDE SOME
EXAMPLES OF SOME OF THIS DATA
THAT HAS BEEN PROVIDED BACK UPON
REQUEST.
SO FOR EXAMPLE, IN MICHIGAN, WE
SPOKE TO SOME CONGRESS PEOPLE
REGARDING WHAT THE STATE WAS OF
SICKLE CELL DISEASE IN MICHIGAN.
SO WE PREPARED A FACT SHEET TO
SAY THIS IS HOW MANY PEOPLE WE
HAVE, TWO HAS BEEN ENROLLED IN
MEDICAID AND HEALTHCARE
UTILIZATION.
THIS IS A DATA BRIEF ABOUT
SICKLE CELL DISEASE IN GEORGIA
WHERE PEOPLE ARE LIVING, HOW OLD
FOLKS ARE, WHAT METRO ATLANTA
COUNTIES PEOPLE ARE LIVING IN.
I COULD GO ON AND ON WITH THESE,
BUT HERE'S JUST A COUPLE MORE
EXAMPLES.
MEDICAID COVERAGE PATTERNS FOR
PEOPLE WITH SICKLE CELL DISEASE
IN CALIFORNIA AND GEORGIA, CAN
REALLY THINK ABOUT PEOPLE
INSURED FOR AT LEAST ONE MONTH,
WHERE THOSE GAPS ARE AND HOW WE
CAN THINK ABOUT CLOSING THOSE
GAPS.
DATA FOR VASO -- ARE
SOCIOECONOMIC FACTORS RELATED TO
EMERGENCY DEPARTMENT UTILIZATION
FOR CALIFORNIANS WITH SICKLE
CELL DISEASE?
THERE'S A LOT OF DIFFERENT WAYS
THAT THIS DATA CAN BE LEVERAGED
TO PROVIDE ORGANIZATIONS WITH
THE EVIDENCE THAT THEY NEED TO
INFLUENCE POLICY.
AND AGAIN, THE POLICY
CONTRIBUTIONS GO PAST JUST THE
DATA.
THERE'S A LOT OF EXPERTISE ON
THESE SCDC TEAMS.
A LOT OF THE DATA AND
STAKEHOLDER EXPERTISE, FOLKS
HAVE SERVED WITH COMMITTEE FOR
THE STRATEGIC PLAN AND
BLUEPRINT, PARTICIPATION IN
GOVERNOR APPOINTED COUNCILS, YOU
HEARD MARIAM PAWK ABOUT THAT, T,
MEETINGS WITH LEGISLATORS AT
MULTIPLE LEVELS, SO REALLY THE
DATA AS WELL AS THE DEEP
KNOWLEDGE ON THESE SCDC TEAMS
AND WIDE VARIETY OF STAKEHOLDERS
INVOLVED CAN HELP INFORM
DIFFERENT POLICIES AND TARGETS.
SO AGAIN, I WANT TO TAKE A
MOMENT TO THANK MDHHS
COLLABORATORS, MARY, ISABELLE,
TERRA, KEVIN, MICHAELLA, AND
THANK YOU VERY MUCH FOR THE
OPPORTUNITY TO TALK ABOUT SCDC
IN MICHIGAN.
>> THANK YOU SO MUCH, DOM AND
SARAH.
I THINK WHAT IS GOING ON IN
MICHIGAN IS EXACTLY THE TYPE OF
PROJECT AND EXACTLY THE TYPE OF
ACTIVITY THAT THIS PROGRAM WAS
ESTABLISHED FOR, AND WE'RE JUST
SO DELIGHTED TO HAVE THE
OPPORTUNITY FOR THIS TO BE
HAPPENING.
SO MOVING ON TO OUR FINAL
PRESENTATION FOR TODAY FROM THE
GEORGIA SCDC TEAM, WE HAVE
DR. ANGIE SNYDER.
SHE HAS BEEN, WOULDING ON THIS
PROJECT FOR 11, 12 YEARS AT THIS
POINT, SO WE'VE BEEN ON THIS
ROAD TOGETHER FOR A VERY LONG
TIME.
AND ANGIE IS GOING TO SHARE SOME
OF OUR NEWER ACTIVITIES WITH YOU
THAT ARE QUITE EXCITING.
SO WE'VE HAD THIS CORE DATASET
THAT WE'VE BEEN WORKING WITH AND
WE'VE HAD KIND OF THESE CORE
SOURCES OF DATA FOR A LONG TIME
THAT ARE PART OF SCDC BUT WITH
THE RECENT PANDEMIC, WE WERE
ALSO ABLE TO LEVERAGE THAT CORE
DATA TO LINK WITH INFORMATION
SPECIFIC TO COVID-19 AND USE
THAT LINKAGE CAPABILITY AS A WAY
TO BETTER UNDERSTAND THE IMPACT
OF COVID ON THE SICKLE CELL
DISEASE POPULATION.
SO ANGIE IS GOING TO TALK ABOUT
A COUPLE OF DIFFERENT WAYS THAT
WE'RE EXPLORING THE DATA AND
BETTER UNDERSTANDING THE IMPACT
OF THE PANDEMIC FOR SICKLE CELL
DISEASE.
THANKS, ANGIE.
>> THANK YOU.
GREAT.
SO AS MARY SAID, I'M ANGIE
SNYDER.
I'M FROM GEORGIA STATE
UNIVERSITY, AND I'M THE PI OF
THE GEORGIA PROGRAM AND LIKE SHE
SAID, I'VE BEEN WORKING WITH
MARY AND CALIFORNIA FOR A LONG
TIME DOING ALL THIS WORK.
SO IT'S EXCITING TO SEE HOW
OTHER STATES ARE COMING ALONG
NOW.
IT'S REALLY EXCITING.
AND I'M GOING TO PRESENT THIS
WORK AND GEORGIA IS PART OF IT,
BUT IT HAS LOTS OF COLLABORATORS
FROM THESE OTHER STATES AS WELL.
SO AS MARY MENTIONED, WE HAVE
THREE ONGOING PROJECTS RIGHT
NOW, LOOKING AT SORT OF THE
INTERSECTION OF SICKLE CELL AND
COVID-19.
WE HAVE ONE PAPER THAT'S
COMPLETED AND I'M GOING TO TALK
TO YOU ABOUT THAT TODAY THAT'S
LOOKING AT THE OUTCOMES OF
COVID-19 IN PEOPLE WITH SICKLE
CELL DISEASE AND TRAIT.
AND THIS IS USING THE STATE'S
COVID-19 SURVEILLANCE SYSTEMS.
WE HAVE ANOTHER TWO PAPERS THAT
ARE IN PROCESS, AND I'LL SHARE
WITH YOU A LITTLE BIT OF
PRELIMINARY DATA FROM THOSE.
ONE LOOKS AT TRENDS AND
CHARACTERISTICS OF EMERGENCY
DEPARTMENT UTILIZATION BEFORE
AND DURING THE PANDEMIC, EARLY
PANDEMIC.
AND THEN THE OTHER LOOKS AT
ACCESS TO AND USE OF TELEHEALTH
DURING THE COVID-19 PANDEMIC.
I DON'T HAVE RESULTS YET, I'M
JUST GOING TO TELL YOU WHAT
WE'RE PLANNING TO DO.
AS MARY AND SEVERAL OF MY
COPRESENTERS MENTIONED, THIS
IS -- THE SCDC PROGRAM OFFERS
LOTS OF BENEFITS TO US.
ONE OF THOSE BEING THAT WE CAN
LINK WITH ADDITIONAL
SURVEILLANCE DATA IN THE STATE
TO LOOK AT DIFFERENT OUTCOMES OF
INTEREST.
AND I THINK SARAH MENTIONED ONE
OF THE OTHER DATASETS THAT SHE
AND I KNOW GEORGIA HAS ALSO
LINKED WITH IS OUR IMMUNIZATION
REGISTRIES.
BUT IT OFFERED US THE PERFECT
OPPORTUNITY TO LOOK AT AN
EMERGING THREAT LIKE COVID-19.
AND ANOTHER SURVEILLANCE SYSTEM
OR TRACKING SYSTEM THAT SOME
STATES ARE ALSO COLLECTING DATA
ON IS THE PRESCRIPTION DRUG
MONITORING PROGRAM.
YOU COULD THINK OF A LOT OF
DIFFERENT PLACES WHERE WE MIGHT
WANT TO LINK TO ADDITIONAL DATA
TO ANSWER SPECIFIC QUESTIONS
ABOUT INDIVIDUALS WITH SICKLE
CELL DISEASE.
THE OTHER THING I WANTED TO
STRESS ABOUT OUR DATA IS THE
LONGITUDINAL NATURE OF IT.
AND I KNOW THAT GEORGIA AND
CALIFORNIA HAVE THE MOST
LONGITUDINAL DATA BECAUSE WE'VE
BEEN PARTICIPATING IN THIS WORK
FOR THE LONGEST PERIOD OF TIME.
BUT ONE OF THESE STUDIES THAT
WE'RE DOING, THE ED1, WI ONE, WL
SHOW THE ABILITY TO TRACK
CHANGES IN CARE OVER TIME CAN
ALSO BE REALLY HELPFUL.
SO WE'RE GOING TO SHOW YOU HOW
WE'RE LOOKING PRE AND POST THE
COVID-19 PANDEMIC, BUT YOU COULD
IMAGINE A LOT OF OTHER THINGS
THAT YOU MIGHT WANT TO LOOK AT,
DIFFERENT POLICY CHANGES OR
DIFFERENT THINGS THAT ARE
HAPPENING, DOES THAT CHANGE THE
WAY INDIVIDUALS WITH SICKLE CELL
DISEASE ACCESS CARE.
AND I'LL JUST HIGHLIGHT BECAUSE
THE COVID-19 PANDEMIC BECAME
PART OF HEALTHCARE UTILIZATION
DATA, THEY CREATED A NEW
ADMINISTRATIVE CODE FOR IT
BECAUSE WE'RE COLLECTING
ADMINISTRATIVE DATA AS PART OF
OUR SURVEILLANCE PROJECT, WE CAN
ALSO USE THOSE CODES TO SORT OF
TRACK THE INTERACTION WITH
INDIVIDUALS WITH SICKLE CELL
DISEASE.
SO THIS IS THE FIRST PAPER I
MENTIONED.
THIS ONE IS COMPLETED, AND IT'S
BEEN SUBMITTED, IT'S UNDER
REVIEW, AND THIS IS LOOKING AT
OUTCOMES OF COVID-19 IN NEWBORN
SCREENING COHORTS OF SICKLE CELL
DISEASE AND TRAIT.
AND ALL THESE WONDERFUL
CO-AUTHORS HAVE DONE THIS WORK
WITH ME.
OBJECTIVES OF THIS STUDY WERE TO
DESCRIBE THE COHORTS OF
INDIVIDUALS FROM TWO STATEWIDE
NEWBORN SCREENING COHORTS A
TRADE AND SICKLE CELL DISEASE
WITH OUR STATE COVID-19 TRACKING
DATA.
AND WE DID THIS IN TWO STATES,
MICHIGAN AND GEORGIA, FROM 2020
TO 2021.
AND WE HAVE THREE COHORT OF
INDIVIDUALS, PERSONS WITH SICKLE
CELL DISEASE THAT ALSO REPORTED
A POSITIVE TEST FOR COVID-19,
PERSONS WITH TRAIT THAT REPORTED
A POSITIVE TEST WITH COVID-19,
AND THEN PERSONS WITH NORMAL
HEMOGLOBIN AND COVID-19.
SO FIRST WE JUST WANTED TO LOOK
AT RATES WITHIN THESE THREE
COHORTS OF HOSPITALIZATION AND
DEATH, AND THEN -- AND WITH
POSITIVE TESTS, AND THEN WE ALSO
WANTED TO RUN A MULTIVARIATE
MODEL WHERE WE ESTIMATED THE
ODDS OF HOSPITALIZATION AND
DEATH, AND FOR THIS -- FOR THE
MODELING, WE RESTRICTED IT TO
THE BLACK RACE ONLY BECAUSE
THERE'S SO FEW INDIVIDUALS IN
BOTH OF OUR STATES THAT WERE NOT
BLACK WHO HAD SICKLE CELL
DISEASE OR SICKLE CELL TRAIT.
SO AGAIN AS EVERYONE'S
MENTIONED, THERE IS NO
POPULATION-BASED REGISTRY FOR
SICKLE CELL DISEASE OR TRAIT, SO
WHILE ALL THE OTHER STUDIES THAT
HAVE BEEN DONE WITH SICKLE CELL
AND COVID-19 ARE REALLY, REALLY
IMPORTANT, ALL OF THEM ARE VERY
IMPORTANT, THEIR THEY'RE BIASED
IN CLINICAL CARE SETTINGS WHERE
PEOPLE ARE DOING RESEARCH.
THIS ONE IS -- THIS -- OUR
DATASET ALLOWS TO YOU LOOK AT
ALL INDIVIDUALS WITH SICKLE CELL
DISEASE TO GET POPULATION-BASED
ESTIMATES.
WHY IS THIS REALLY IMPORTANT,
ALSO TO LOOK AT FOLKS WITH
TRAIT, IS OF COURSE COVID-19
APPEARS TO HAVE A SEVERE EFFECT
ON THOSE WITH DISEASE, IT HAS
UNKNOWN EFFECTS ON THOSE WITH
TRAIT, AND THE PATHOPHYSIOLOGY
OF TRAIT MAY TARGET SOME OF THE
SAME SYSTEMS AND ORGANS AS
COVID-19 AND SO IT WAS IMPORTANT
FOR US TO UNDERSTAND IF
INDIVIDUALS WITH TRAIT WERE ALSO
AT INCREASED RISK.
AND WE ALSO WANTED TO SORT OF
TEST THE THEORY OF CAN WE LINK
THESE DATA SOURCES, AND WE DID
IT VERY COLLABORATIVELY IN BOTH
GEORGIA AND MICHIGAN WHEREAS
SARAH DESCRIBED IN MICHIGAN THEY
HAVE A VERY CLOSE RELATIONSHIP
WITH THEIR HEALTH DEPARTMENT
FOLKS, WE ALSO DO IN GEORGIA,
AND IT'S REALLY THE HEALTH
DEPARTMENT INDIVIDUALS WHO DID
THE LINKING BEHIND THEIR
FIREWALLS.
THEY DIDN'T ACTUALLY -- WE
DIDN'T HAVE TIME TO SHARE
COVID-19 DATA WITH US AT THE
UNIVERSITY.
SO ALL THE DATA ANALYSIS WAS
DONE BY THE INDIVIDUAL AT THE
HEALTH DEPARTMENTS.
AND CALIFORNIA HELPED TO
COORDINATE AND HELPED TO WRITE
THE PAPER.
SO A LITTLE BIT MORE ABOUT OUR
METHODS.
AS I MENTIONED, WE HAVE THREE
DISEASE -- WE HAVE THREE
COHORTS, ONE COHORT WITH SICKLE
CELL DISEASE, ONE WITH SICKLE
CELL TRAIT AND ONE WITH NORMAL
HEMOGLOBIN.
IN GEORGIA, WE REALLY ONLY HAVE
CHILDREN, IT'S REALLY ONLY A
PEDIATRIC COHORT BECAUSE OUR
NEWBORN SCREENING DATA ONLY GOES
BACK ELECTRONICALLY TO 2008.
AND SO WE NEEDED TO GO BACK TO
OUR NEWBORN SCREANING DATA
BSCREENING DATABECAUSE WE ALSO O
COLLECT INFORMATION ON
INDIVIDUALS WITH TRAIT BECAUSE
WE DON'T HAVE IT IN OUR
SURVEILLANCE SYSTEM AND ALSO
NEEDED TO CONFIRM INDIVIDUALS
HAD NORMAL HEMOGLOBIN.
MICHIGAN HAS SLIGHTLY MORE
HISTORICAL DATA, THEY WERE ABLE
TO GO BACK TO 1987 AND THEY HAVE
INDIVIDUALS AS OLD AS 33 IN
THEIR DATA.
YOU CAN SEE BASED ON OUR
RESULTS, MICHIGAN HAS MORE --
LARGER POPULATIONS AND ALSO
LARGER OUTCOMES OF INTEREST LIKE
HOSPITALIZATION AND DEATH
BECAUSE THEY HAVE AN OLDER
COHORT THAN WE DO IN GEORGIA.
AND AGAIN WE LINK TO EACH OF OUR
STATES COVID-19 CONFIRMED CASE
AND THESE ARE -- THE STATES
QUICKLY GOT ORGANIZED AROUND
DOING SURVEILLANCE FOR COVID-19,
SO THESE ARE ALL PEOPLE THAT HAD
A POSITIVE PCR TEST FOR
COVID-19.
FROM MARCH 2ND, 2020 TO NOVEMBE.
SO WE TRIED NOT TO INCLUDE THE
OMICRON AND WE ALSO WANTED TO
GET THE RESULTS OUT SINCE WE'RE
STILL KIND OF IN THE MIDDLE OF
THE PANDEMIC.
WE CUT OFF DATA COLLECTION AT
NOVEMBER 30TH OF LAST YEAR.
AND AGAIN OUR LOGISTIC
REGRESSION MODELS FOR HOSPITAL
AND DEATH, WITH HE RESTRICTED TO
BLACK POPULATIONS, WE USED
GENERALIZED ESTIMATING EQUATION
MODELING IN MICHIGAN BECAUSE
THEY HAVE SOME REINFECTION DATA.
GEORGIA JUST HAD VERY MINIMAL
REINFECTION DATA, SO WE JUST --
WE DIDN'T INCLUDE REINFECTIONS
AND WE USED A STANDARD LOGISTIC
REGRESSION MODEL.
SO THESE ARE OUR RESULTS.
THESE ARE DESCRIPTIVE STATISTICS
SO YOU CAN LOOK AT MALES AND
FEMALES AND BY TWO DIFFERENT AGE
COHORTS BECAUSE REMEMBER WE HAVE
A PRETTY YOUNG POPULATION.
AND YOU CAN SEE IT BY RACE, BUT
YOU CAN SEE THAT THE PREDOMINANT
NUMBER OF FOLKS IN BOTH THE
SICKLE CELL CATEGORIES ARE
PEOPLE THAT IDENTIFY AS BLACK.
SO WHEN WE DID THE MODELING
AGAIN, WE JUST DID IT WITH THE
BLACK POPULATIONS IN ALL.
BUT YOU CAN SEE THAT THE RATES
IN GEORGIA, THESE ARE THE
GEORGIA RESULTS, THEY LOOK
PRETTY SIMILAR IN TERMS OF THE
TOTAL NUMBER OF FOLKS THAT ARE
TESTING POSITIVE, THE PERCENTAGE
OF INDIVIDUALS TESTING POSITIVE,
AND THE PERCENTAGE OF THOSE THAT
ENDED UP HOSPITALIZED IN THE
TRAIT AND THE NORMAL HEMOGLOBIN,
THAT'S NOT EVEN CONTROLLING FOR
ANY OTHER COVARIATES, AND SICKLE
CELL DISEASE, OF COURSE THE RATE
IS MUCH HIGHER IN TERMS OF
TESTING POSITIVE AND IN TERMS OF
THE INDIVIDUALS THAT ARE
SUBSEQUENTLY HOSPITALIZED.
THESE ARE THE RATES FOR
MICHIGAN.
SOMEWHAT SIMILAR TO GEORGIA, THE
SICKLE CELL DISEASE POPULATION,
OF COURSE THE RATES ARE MUCH
HIGHER.
IT LOOKS LIKE IN MICHIGAN
OVERALL, THAT MORE INDIVIDUALS
ARE TESTING POSITIVE FOR
COVID-19, BUT IN THE NORMAL
HEMOGLOBIN GROUP, BUT SLIGHTLY
LESS OF THEM ARE BEING
HOSPITALIZED.
BUT LET'S ALSO GO TO THE NEXT
SLIDE AND LOOK AT THE
MULTIVARIATE MODELS.
SO THESE ARE THE ODDS RATIOS OF
HOSPITALIZATION AND MORTALITY IN
BOTH GEORGIA AND MICHIGAN.
AND SO -- WELL, AND I SHOULD SAY
MORTALITY IS ONLY IN MICHIGAN
BECAUSE GEORGIA JUST DID NOT
HAVE ENOUGH DEATHS TO MODEL.
SO THE TOP PART IS THE ODDS OF
HOSPITALIZATION IN GEORGIA AND
MICHIGAN.
YOU CAN SEE THAT IN THE -- THAT
THE RATES ARE -- COMPARING THE
SICKLE CELL POPULATION TO
INDIVIDUALS WITH NORMAL
HEMOGLOBIN, THAT THE RATES ARE
MUCH HIGHER, EVEN WHEN YOU
CONTROL FOR AGE AND SEX.
BUT THE ADJUSTED ODDS FOR TRAIT
ARE PRETTY MUCH RIGHT ON THE 1,
SO THEY'RE NOT SIGNIFICANT AT
ALL.
AND THEN ALSO THE SAME FOR
MICHIGAN WITH THE MORTALITY
DATA, YOU CAN SEE THE CONFIDENCE
INTERVALS OVERLAP WITH ONE.
SO THERE'S NO SIGNIFICANCE FOR
TRAIT IN TERMS OF ANY DIFFERENCE
IN HOSPITALIZATION OR MORTALITY,
BUT THERE IS A DIFFERENCE, A
HIGHER RATE FOR THOSE WITH
SICKLE CELL DISEASE.
SO THAT'S THE RESULTS OF THAT
STUDY.
I WILL ALSO GIVE YOU A PREVIEW
OF SOME PRELIMINARY DATA ON
TRENDS AND CHARACTERISTICS OF
EMERGENCY DEPARTMENT USE PRE AND
DURING THE COVID-19 PANDEMIC
AMONG INDIVIDUALS WITH SICKLE
CELL DISEASE.
FOR THIS STUDY, WE HAVE GEORGIA,
CALIFORNIA, MICHIGAN AND
TENNESSEE CO-AUTHORS.
SO AGAIN, THE GOAL OF THIS WORK
IS TO LOOK AT TRENDS AND
CHARACTERISTICS OF ED VISITS
DURING -- PRE AND DURING THE
PANDEMIC AMONG INDIVIDUALS WITH
SICKLE CELL DISEASE.
WE'RE LOOKING AT OVERALL RATES
OF ED UTILIZATION, AND THEN
DIFFERENCES ACROSS DIFFERENT
SOCIODEMOGRAPHIC
CHARACTERISTICS.
WHY IS THIS IMPORTANT?
ED IS REALLY AN IMPORTANT SOURCE
OF CARE FOR THOSE WITH SICKLE
CELL DISEASE, AND WE'RE NOT
REALLY SURE WHAT HAPPENED TO ED
UTILIZATION DURING THE PANDEMIC.
WE COULD ARGUE WHY IT MIGHT
INCREASE AND WE CAN ARGUE WHY IT
MIGHT DECREASE.
AGAIN, WE TOOK THE SICKLE CELL
COHORTS WERE DEFINED FOR EACH
STATE FOR ALL INDIVIDUALS THAT
MET OUR -- AND IF YOU REMEMBER
THE CASE DEFINITION, IT WOULD BE
CONFIRMED CASES AND THE PROBABLE
CASES.
FOR CALENDAR YEAR 2019.
WE WANTED TO MAKE SURE THEY WERE
INSURED BY MEDICAID IN EACH
STATE BECAUSE WE WANTED TO MAKE
SURE THEY WERE IN THE STATE
DURING THE WHOLE TIME PERIOD,
AND THEN WE ALSO -- SOME
FOLKS -- SOME STATES HAD A
LITTLE BIT OF DIFFICULTY WITH
THEIR E D-DAY TA.
D DATA.
SOME STATES USED THEIR ED DATA
FOR THIS, THE DATA MARIAM TALKED
ABOUT IN HER PRESENTATION.
SO WE WANTED TO MAKE SURE THEY
WERE INSURED BY MEDICAID FOR 18
OR MORE OF THE 24 MONTHS BETWEEN
JANUARY 2019 AND DECEMBER 2020.
WE LOOKED AT THE MONTHLY RATE OF
ANY ED UTILIZATION PER 1,000
INDIVIDUALS WITH SICKLE CELL
DISEASE.
SO WE'RE BASICALLY LOOKING AT
MONTHLY RATES OF ED USE
PRE-PANDEMIC, WHICH WOULD BE
JANUARY 2019 TO FEBRUARY 2020,
AND THEN DURING THE PANDEMIC,
AND I WILL SAY MARCH BUT IT'S
REALLY APRIL, MARCH IS KIND OF
IN THAT GREY ZONE.
APRIL TO DEES DECEMBER OF 2020.
AND WE USED AN INTERRUPTED TIME
SERIES, FOR THOSE OF YOU THAT
ARE METHODOLOGISTS, GENERALIZED
LINEAR MODEL.
WE USED POISSON LINK FUNCTION
AND OFFSET USING THE LOG OF THE
COHORT SIZE.
WE ALSO SEASONALLY ADJUSTED TO
LOOK AT COHORT TRENDS.
AGAIN, WHAT YOU'RE LOOKING AT
WHEN I SHOW YOU THE PRELIMINARY
RESULTS FOR CALIFORNIA AND
GEORGIA ARE THE MEDIAN TOTAL
NUMBER OF ED VISITS, AND WE ALSO
ARE GOING TO LOOK AT THEM BY
AGE, SEX, RACE AND ETHNICITY.
WE HAVE SICKLE CELL GENOTYPE FOR
SOME OF THEM.
AND WE HAVE PAYER FOR THE ED
VISITS.
AND THEN WE ALSO PLAN TO LOOK AT
THOSE THAT RESULTED IN INPATIENT
ADMISSIONS TO THE HOSPITAL, ALSO
THOSE THAT WERE TREAT AND
RELEASE VISIT, AND THEN THE FIVE
MOST FREQUENTLY OCCURRING
PRIMARY DISCHARGE DIAGNOSES.
WE CAN ALSO LOOK AT WHETHER THE
HOSPITALIZATION WAS DUE TO
COVID-19 OR NOT, OR WHETHER THE
ED VISIT WAS DUE TO COVID-19 OR
NOT.
SO AGAIN, THESE ARE JUST
PRELIMINARY.
WE ONLY HAVE RESULT FROM GEORGIA
AND CALIFORNIA.
LET ME SEE IF I CAN EXPLAIN TO
YOU WHAT YOU'RE SEEING.
AGAIN, THE LINES ARE SQUIGGLY
BECAUSE THEY'RE ADJUSTED AND
THERE IS SOME SEASONALITY TO ED
USE.
BUT YOU CAN SEE THE LITTLE --
THE BLACK LINE IS WHAT WAS GOING
ON PRE-PANDEMIC.
THE RED LINE IS ONCE THE
PANDEMIC STARTED.
THE DOTTED LINE WOULD BE WHAT WE
WOULD EXPECT IF THERE WAS NO
DISRUPTION, IF THERE WAS NO
COVID-19 PANDEMIC, THAT WOULD BE
WHAT WE WOULD EXPECT TO SEE
BASED ON THE SEASONAL TREND.
GOING ON.
SO YOU CAN SEE IT'S INTERESTING
THAT THE SLOPES OF THE LINES IN
CALIFORNIA AND GEORGIA DON'T
EVEN LOOK THE SAME.
SO BOTH OF THEM CLEARLY, WHEN
THE PANDEMIC SORT OF HIT IN
APRIL, THEY HAD A DISRUPTION.
THERE WAS A LOT LESS ED VISITS,
AND THEN IN GEORGIA IT LACKS
LIKE THEY WERE APPROACHING BY
THE END OF LAST YEAR, THEY WERE
APPROACHING BACK TO NORMAL, BUT
IN CALIFORNIA, THEY LOOK LIKE
THEY'RE GOING THE OPPOSITE
DIRECTION, THAT THERE'S EVEN
LESS FOLKS AT THE END OF LAST
YEAR THAT WERE UTILIZING THE ED
THAN EXPECTED.
SO LOTS OF QUESTIONS, WE'RE
EXCITED TO SEE WHAT THE OTHER
STATES COME UP WITH, AND THIS
SUGGESTS THAT MAYBE SOME OF THE
LOCAL POLICIES OR -- THAT THAT
MIGHT BE CHANGING HOSPITAL
UTILIZATION MORE THAN EVEN THE
SICKLE CELL STATUS OF THE
INDIVIDUALS IN EACH OF THE
STATES.
SO IT QUITE INTERESTING.
AND THEN I SAID WE WERE GOING TO
TEST FOR DIFFERENCES.
THE ONLY ONE THAT LOOKS QUITE
INTERESTING, IT'S A TREND THAT
WE SAW BOTH IN GEORGIA AND
CALIFORNIA, IS THAT THE DECREASE
IN ED VISITS IS REALLY DRIVEN BY
THE PEDIATRIC POPULATIONS.
EVEN IN CALIFORNIA, IT'S EVEN
THE YOUNGEST, YOU KNOW, IT THE
ZERO TO 10-YEAR-OLDS.
THEY'RE HAVING WAY LESS ED
VISITS THAN THEY HAD BEEN,
ALMOST A 45% DECREASE IN
GEORGIA, THAT THEY WERE HAVING
PRIOR TO THE PANDEMIC.
THE OTHER THING I WILL JUST SAY,
WE'VE SCANNED THROUGH ARE THERE
DIFFERENCES IN THE PRIMARY
DIAGNOSIS OF THE INDIVIDUALS
WHEN THEY'RE HAVING THESE ED
VISITS, AND REALLY THERE AREN'T
ANY DIFFERENCES, IF WE JUST DID
LIKE THE TOP FIVE DIAGNOSES FOR
EACH OR EVEN THE TOP 10, THEY
PRETTY MUCH LOOK THE SAME PRE
AND DURING THE PANDEMIC.
SO MORE TO COME ON THIS.
IT'S REALLY INTERESTING.
I'D BE INTERESTED TO SEE IF
ANYBODY HAS ANY OTHER THOUGHTS
ABOUT WHY WE MIGHT BE SEEING
THESE DIFFERENT UTILIZATION
PATTERNS.
THEN FINALLY, WE DON'T HAVE
PRELIMINARY RESULTS FOR THIS,
BUT WE'RE ALSO LOOKING AT THE
USE OF TELEHEALTH FOR
INDIVIDUALS DURING COVID-19 AS
WELL.
SOME OF THAT MIGHT BE
INTERACTING WITH THE ED VISITS,
WE'RE NOT SURE, BUT WE WANT TO
DESCRIBE ACCESS TO AND USE OF
TELEHEALTH AMONG INDIVIDUALS
WITH SICKLE CELL DURING THE
COVID-19 PANDEMIC.
AND WE'RE GOING TO LOOK AT
CHARACTERISTICS OF THE
TELEHEALTH USE, THE FREQUENCY OF
THE USE, THE CHARACTERISTICS OF
THE PROVIDERS, THE SPECIALTY,
LOOK AT DEMOGRAPHICS OF THE
INDIVIDUALS AND AREA LEVEL
CHARACTERISTICS AS WELL.
I THINK IT'S PRETTY SELF
EXPLANATORY, BUT WE JUST SORT OF
WANT TO KNOW IF ANY OF THAT
TELEHEALTH USE THAT MAY HAVE
OCCURRED DURING THE PANDEMIC IS
REDUCING ANY SORT OF BARRIERS
THAT INDIVIDUALS MAY HAVE
EXPERIENCED.
SO THAT WILL BE VERY EXCITING
TOO, ONCE WE START LOOKING AT
THAT.
I KNOW FROM JUST LOOKING AT
PRELIMINARY DATA, GEORGIA WAS
USING A FAIR AMOUNT OF
TELEHEALTH BEFORE, BUT MOST OF
THE OTHER STATES, NOT A LOT OF
TELEHEALTH IN THE SICKLE CELL
POPULATION, BUT I'M SURE THAT
THAT HAS INCREASED AND CHANGED
SINCE THE PANDEMIC.
SO I THINK THAT WAS MY LAST
SLIDE.
AND THAT'S ALSO MY INFORMATION,
IF ANYBODY WOULD LIKE TO CONTACT
ME IN THE FUTURE.
AND I GUESS I'LL TURN IT BACK TO
YOU, MARY, AND SEE IF THERE'S
ANY OTHER QUESTIONS.
>> THANK YOU SO MUCH, ANGIE.
AND HUGE THANKS TO EVERYBODY WHO
WAS ON THE PANEL TODAY.
SO WE HAVE BEEN RECEIVING A LOT
OF QUESTIONS THROUGH THE Q & A.
I THINK ALL OF THOSE HAVE BEEN
ANSWERED AT THIS POINT.
IF YOU NEED ADDITIONAL
INFORMATION, YOU'RE MORE THAN
WELCOME TO REACH OUT TO
INDIVIDUAL PANELISTS OR YOU CAN
CONTACT ME AND I WILL CONNECT
WITH YOU FOLKS.
THERE ARE SEVERAL QUESTIONS IN
THE CHAT AS WELL.
IT LOOKS LIKE THOSE HAVE BEEN
ANSWERED TOO.
WE CAN TAKE MORE QUESTIONS.
IF NOT, I CAN GO THROUGH SOME OF
THE QUESTIONS THAT WERE ASKED
AND THE ANSWERS PROVIDED.
I'M SEEING ONE, WE WISH WE HAD
MEASURES FOR APPROPRIATE ED CARE
VERSUS OPTIONAL ED CARE IN
SICKLE CELL DISEASE.
I'M NOT SURE -- OPTIONAL, I'M
NOT SURE IF THAT WAS SOMETHING
THAT WAS TALKED ABOUT.
BUT YES, CERTAINLY MEASURES FOR
APPROPRIATE CARE WOULD BE
FANTASTIC.
IT DOESN'T LOOK LIKE WE'VE
GOT -- I THINK THEY'VE ALL BEEN
CHECKED IN THE CHAT, SO SOME OF
THE TYPES OF QUESTIONS THAT HAVE
COME IN THROUGH THE Q & A, JUST
TO JUST SHARE WITH OTHERS,
THERE'S QUESTIONS ABOUT CAN
KNOWLEDGE BE EXAINGED EXCHANGEH
OTHER PROGRAMS?
THIS WAS SPECIFIC TO SICKLE IN
AFRICA BUT I'M GOING TO EXPAND
THE QUESTION TO ASKING ABOUT
OTHERS, SO CERTAINLY THE
METHODOLOGIES THAT ARE USED HERE
ARE AND ARE NOT RELEVANT ACROSS
STATES AND ACROSS COUNTRIES,
EVERYONE IN THIS PROGRAM LOVES
TO TALK ABOUT IT, AND WILL
PROBABLY TALK YOUR EAR OFF IF
YOU GET IN TOUCH WITH ANY OF US,
SO WE CAN ABSOLUTELY SHARE
INFORMATION.
WE CAN SHARE HOW THE DATA IS
BEING A SED, WE CAN TALK ABOUT
CONFIDENTIALITY.
PLEASE GET IN TOUCH WITH US AND
WE WILL CERTAINLY DO THAT.
THERE WAS LOTS OF QUESTIONS
ABOUT KIND OF INTERPRETING THE
DATA AND WHAT THE DATA MEANS,
AND I WILL SAY SOMETHING THAT
LOOKS TO BE COMMON ACROSS MANY
OF THEM IS, AGAIN, ONE OF THE
UNIQUE ASPECTS OF THIS PROGRAM
IS THAT IT DOES INCLUDE PEOPLE
OF ALL AGE, IT INCLUDES
HEALTHCARE UTILIZATION
REGARDLESS OF WHO PAYS FOR IT,
SO WHETHER IT'S MEDICARE,
MEDICAID, PRIVATE INSURANCE,
SELF PAY, OTHER FORMS OF
INSURANCE, THAT IS ALL CAPTURED
BY THIS PROGRAM.
REALLY --
>> THERE ARE A FEW COMMENTS ON
THE CHAT, I THINK.
MARY, THERE ARE A FEW COMMENTS
IN THE CHAT.
>> ARE THEY NEW?
LET'S SEE.
REGARDING THE NEW -- THAT'S FROM
DOM FOR OTHERS, LETTING YOU KNOW
THAT THE NEW CENTER IN
DETROIT -- NOT SURE IT'S READY
TO BE ANNOUNCED JUST YET BUT
WILL SHARE THIS INFORMATION ONCE
THERE IS INFORMATION AVAILABLE,
AND I WILL BE HAPPY TO GET THAT
OUT TO FOLKS.
AND THEN A COMMENT BACK TO
DR. SU ASKING ABOUT ED CARE THAT
GETS PRETTY CLOSE AT DETERMINING
DIFFERENT MEASURES OF ED CARE.
OH, PAULA TANABE, DO YOU HAVE
YOUR HAND UP?
FEEL FREE TO COME OFF MUTE.
I THINK YOU'RE A PANELIST SO YOU
CAN DO THAT.
>> DOMINIC ANSWERED IT IN THE
CHAT.
>> OH, WONDERFUL.
WONDERFUL.
OKAY.
SO I WILL CLOSE OUT OUR TIME
HERE TODAY.
BUT PLEASE, IF YOU NEED
ADDITIONAL ANSWERS TO YOUR
QUESTIONS OR IF MORE QUESTIONS
COME UP, REACH OUT TO US.
IF YOU HAVE QUESTIONS YOU WOULD
LIKE TO ASK OF THE DATA, YOU CAN
REACH OUT TO ONE OF THE STATES
DIRECTLY AND WORK WITH THEM.
YOU CAN GET IN TOUCH WITH ME.
YOU KNOW, WE'RE HOPEFUL THAT
THIS PROJECT CONTINUES AND
CONTINUES TO INCREASE THE
RESOURCES AND FUNDING AVAILABLE
SO THAT WE CAN EXPAND TO ANSWER
MANY MORE QUESTIONS FOR A LONG
TIME TO COME AND USE THIS
INFORMATION TO CONTINUE
IMPROVING CARE AND ACCESS TO
CARE.
THANKS, EVERYONE, VERY, VERY
MUCH.
>> THANK YOU FOR A GREAT SESSION
ON SURVEILLANCE.
SO NOW WE MOVE TO OUR NEXT PART,
WHICH IS DR. ROBERT GIBSON IS
GOING TO TALK ABOUT FINDINGS
FROM THE SICKLE CELL DISEASE
IMPLEMENTATION CONSORTIUM.
DR. GIBSON.
>> THANK YOU.
IF YOU CAN BRING UP MY SLIDES
AND WE CAN GET STARTED.
I WANT TO WELCOME EVERYBODY AND
THANK THE SPEAKERS THAT YOU'RE
GOING TO HEAR.
BECAUSE WE'RE WORKING UNDER THE
CLOCK, I'M GOING TO ASK ALL OF
OUR PRESENTERS TO STAY ON
SCHEDULE TO THE BEST OF THEIR
ABILITY.
AND I WILL ONLY INTRODUCE EACH
SPEAKER -- EACH PRIMARY SPEAKER
OF EACH SECTION.
ALSO PLEASE USE THE CHAT -- I
GUESS THE Q & A FUNCTION.
WE HAVE SOMEONE MONITORING THAT
AND THEY'LL BE ATTEMPTING TO
EITHER ANSWER THOSE QUESTIONS
LIVE OR TO BE ABLE TO DEAL WITH
THEM AT THE END OF EACH SESSION,
WE HAVE TIME SET ASIDE FOR
QUESTIONS.
SO I'M GOING TO ASK EVERYBODY TO
BE SUCCINCT SO WE STAY ON
SCHEDULE AND TO DO THAT, I'M
GOING TO GO AHEAD AND START.
YOU CAN SEE WHO I AM, AND I'M
SPEAKING TODAY ON BEHALF OF THE
IMPLEMENTATION CO CONSORTIUM.
THIS IS SORT OF A WRAP-UP SLIDE
SHOW OF WHAT WE'VE DONE OVER THE
LAST SIX YEARS, AND TO WHET YOUR
APPETITES FOR WHAT WE'RE GOING
TO DO IN THE FUTURE.
I'M NOT SURE THAT THAT'S THE
NEXT SLIDE, BUT THAT'S OKAY.
THIS SHOWS THE PARTICIPATING
ORGANIZATIONS.
THERE WERE EIGHT DIFFERENT
CENTERS.
SO THE CONSORTIUM HAD A COUPLE
OF SPECIFIC GOALS THAT IT WAS TO
CARRY OUT, AND ONE WAS A NEEDS
ASSESSMENT AND THIS IS JUST SORT
OF A VERY QUICK OVERVIEW OF THAT
NEEDS ASSESSMENT THAT WAS
CONDUCTED SIX YEARS AGO AT THE
START OF THE PROJECT.
JUST TO GIVE YOU SOME IDEA OF
WHAT WE WERE LOOKING AT AND HOW
WE COLLECTED DATA.
WE ALSO WERE CHARGED WITH -- GO
BACK ONE, PLEASE.
WE WERE ALSO CHARGED WITH, AS
WELL AS DOING A BROAD BASED
ASSESSMENT, TO THE STARTING OF A
STREJ INDUSTRY.
REGISTRY.
WE'VE HEARD A LOT OF INFORMATION
THIS MORNING ABOUT REGISTRIES
AND DATA COLLECTION, SO THIS WAS
A PROSPECTIVE REGISTRY WITH OVER
2400 INDIVIDUALS ENROLLED.
THIS IS THE -- THESE ARE THE
BASIC INFORMATION ABOUT THAT
REGISTRY.
AND THE IMPORTANT THING IS GOING
TO BE FOUND ON THE NEXT SLIDE
ABOUT OUR REGISTRY.
SO THE REGISTRY IS THE NOT
STOPPING WITH THE PROJECT.
CURE SC FUNDING IS NOW GOING TO
BE USED TO CONTINUE THIS
REGISTRY, AND IT WILL CONTINUE
TO BE BUILT ON THE CURRENT
PLATFORM.
WE'RE GOING TO CONTINUE TO
COLLECT LONGITUDINAL DATA THAT
INFORMS THE NATURAL HISTORY OF
SICKLE CELL DISEASE.
IT'S GOING TO BE A WELL -- IT'S
A COHORT THAT'S WELL
CHARACTERIZED.
WE'RE LOOKING TO CREATE
AUTOMATED EHR DATA EXTRACTION AS
THIS MOVES FORWARD.
AND THIS WILL BE AVAILABLE --
THIS DATA WILL BE AVAILABLE AT
THE NHLBI BIOLINCC AND BIODATA
CATALYST REPOSITORIES.
I KNOW PEOPLE ARE WORKING ACROSS
ALL OF THE DIFFERENT REGISTRIES
TO MAKE THEM INTEROPERABLE AND I
KNOW THAT THAT'S SOMETHING
THAT'S CERTAINLY SOUGHT AFTER.
SO THIS IS A GREAT BENEFIT OF
THE SCD PROJECT.
ANOTHER USE OF THE REGISTRY DATA
IN AN ONGOING REGISTRY STUDY IS
IN THE FINAL STAGES OF BEING
AWARDED.
THIS HAS BEEN REVIEWED BY NHLBI
AND WE ARE AWAITING FINAL
APPROVAL.
THE PI ON THIS IS JEFF GLOSSBERG
AND THIS IS LOOKING AT THE
IMPACT OF SOME OF THE NEW
MEDICATIONS ON PATIENT OUTCOME
SO THIS IS ANOTHER EXCITING
OUTCOME OF THE STUDY, OF THE
REGISTRY PROJECT.
THE SICKLE CELL CONSORTIUM, IN
ADDITION TO THE REGISTRY, ALSO
HAD THREE DIFFERENT PROJECTS.
THE ALIGN PROJECT, WHICH YOU
WILL BE HEARING ABOUT.
DR. TANABE WILL BE REPORTING OUT
DATA FROM TH THE ALIGN PROJECT,O
IMPROVE MANAGEMENT OF
VASO-OCCLUSIVE EPISODES IN ADULT
EMERGENCY DEPARTMENTS.
SO THE STUDY IS COMPLETING ITS
DATA COLLECTION AND IS BEGINNING
DATA ANALYSIS.
A NUMBER OF PUBLICATIONS ARE
PLANNED IN THE OUTCOMES.
INVESTIGATORS ARE PLANNING
FUTURE GRANT APPLICATIONS TO
CONTINUE THE WORK, AND
DR. TANABE LATER IN THIS SESSION
WILL ACTUALLY BE REPORTING
PRELIMINARY RESULTS.
ANOTHER PROJECT WAS THE MESH
PROJECT, AND THIS WAS LED BY DRS
WILL ALSO BE PROVIDING
PRELIMINARY DATA AT THE --
DURING THE SESSION AS WELL.
SO THE GOALS OF THAT PROJECT
WERE TO IMPROVE PATIENT
ADHERENCE TO HYDROXYUREA,
IMPROVE PROVIDER HYDROXYUREA
PRESCRIBING BEHAVIORS AND
EVALUATE BARRIERS AND
FACILITATORS, AND ALL OF THIS
WAS DONE USING AN APP AND DATA
RECORDER.
SO THE MESH TEAM IS, AGAIN, ALSO
COMPLETING THEIR DATA ANALYSIS,
AND THEY'RE ALSO DEVELOPING
PUBLICATIONS.
THEY HAVE RECEIVED AN ASH BRIDGE
FUNDING GRANT TO CONTINUE THEIR
WORK WHILE THEY RESUBMIT AN
APPLICATION TO NHLBI TO
SPECIFICALLY CONTINUE AND EXPAND
THIS WORK, AND DR. HAWKINS WILL
ALSO BE TALKING ABOUT THEIR
PRELIMINARY DATA.
THE THIRD PROJECT WE WORKED ON
AS PART OF THE CONSORTIUM WAS
GETTING UNAFFILIATED PATIENTS TO
CARE, AND I'M GOING TO SPEAK A
LITTLE BIT ABOUT THAT PROJECT.
SO THE OUTCOMES FROM THE
UNAFFILIATED PROJECT, WE CARRIED
OUT A DELPHI PROJECT WHERE WE
IDENTIFIED THROUGH THE DELPHI
PROCESS CREATED A DEFINITION FOR
WHAT IS TRULY AN UNAFFILIATED
STATUS, AND THEN ALSO TO,
THROUGH THE DELPHI PROCESS, TO
DEFINE A SPECIALIST WHO PROVIDES
CARE FOR INDIVIDUALS WITH SICKLE
CELL DISEASE.
OUT OF THE UNAFFILIATED PROJECT,
A MULTISITE R01 HAS BEEN
DEVELOPED AND FUNDED, DR. CANTOR
IS THE CONTACT PI FOR THAT.
THIS PROJECT WILL BE LOOKING AT
IDENTIFYING WAYS TO ENGAGE
INDIVIDUALS WITH SICKLE CELL
DISEASE IN CARE.
WE ARE ALSO COMPLETING THE
ANALYSIS OF THE QUALITATIVE
STUDY THAT WE CONDUCTED LOOKING
AT PATIENT ENGAGEMENT AND I'LL
BE PRESENTING THAT IN NOT THE
NEXT SESSION BUT THE ONE AFTER.
SO THESE ARE THE FINDINGS FROM
THE DELPHI.
YOU CAN SEE ON THE LEFT A
DEFINITION OF AN INDIVIDUAL WITH
SICKLE CELL DISEASE WHO IS
CONSIDERED UNAFFILIATED.
AND THEN ON THE RIGHT IN BLUE,
THE DEFINITION OF A SICKLE CELL
SPECIALIST.
I'LL GIVE YOU A MOMENT TO LOOK
AT THAT.
SO THIS IS A LITTLE BIT OF AN
OVERVIEW OF THE PROJECT THAT I
DESCRIBED THAT DR. CANTER WILL
BE RUNNING.
IT'S CALLED RECIPE FOR SHORT.
AND THIS WILL CONTINUE THE
EFFORTS AT ADAPTING EXISTING
IMPLEMENTATION STRATEGIES USED
IN OTHER CHRONIC DISEASES FOR
SICKLE CELL DISEASE.
SO IT'S LARGELY AN INL PLEM
IMPLEMENTATION SCIENCE PROJECT.
THESE ARE THE SITES FOR THE
RECIPE PROJECT, AND YOU SEE
THERE'S A NICE DISTRIBUTION AND
THIS OVERLAPS VERY NICELY WITH
THE SLIDE THAT WAS PRESENTED IN
THE PREVIOUS PRESENTATION FROM
THE CDC PROJECT OVERLAPPING
WHERE THERE ARE LARGE
INDIVIDUALS WITH SICKLE CELL
DISEASE.
SO OVERALL, IN CONCLUSION, AND I
AM JUST ABOUT OVER TIME.
SO THESE ARE THE OUTCOMES OF THE
SICKLE CELL CONSORTIUM.
WE'VE HAD A GREAT OUTCOME.
I'VE JUST DESCRIBED HOW THE
PROJECTS WILL GO ON IN THE
FUTURE.
AND THEN THE LAST THING WE WANT
TO CALL ATTENTION TO IS WE'VE
HAD A NUMBER OF WONDERFUL
DIVERSITY SUPPLEMENT TRAINEES AS
WELL AS ONE PRIDE TRAINEE.
JUST WANT TO SHOUT OUT THESE
INDIVIDUALS WHO HAVE WORKED ON
OUR PROJECT OVER THE LAST SIX
YEARS AND THE BENEFITS TO THEIR
CAREER AND TO SCIENCE IN
GENERAL.
I THINK I'VE RUN OUT OF TIME, SO
WE'LL TRY AND ANSWER QUESTIONS
IN THE CHAT.
OR WE'LL PICK THEM UP LATER.
NOW I WANT TO INTRODUCE
DR. LEWIS HSU WHO IS LEADING US
WITH THE VALUE OF COMMUNITY
STAKEHOLDERS.
>> THANK YOU, DR. GIBSON.
CAN I GET MY SLIDES BACK UP?
BRIDGET REYNOLDS IS MY PARTNER
AND SHE'LL PRESENT THE LATTER
HALF.
WHILE WE'RE WAITING FOR THE
SLIDES TO COME UP.
I'M PLEASED AND HONORED TO
CO-PRESENT THIS SESSION THAT'S
CALLED THE VALUE OF COMMUNITY
STAKEHOLDER ADVISORS IN
TRANSFORMING SICKLE CELL CARE.
A COLLABORATIVE JOURNEY.
AND OUR GOAL IN THIS IS TO
HIGHLIGHT THE VALUE OF
STAKEHOLDER ADVISORS FOR THIS
SICKLE CELL DISEASE
IMPLEMENTATION CONSORTIUM
PROJECT, AND WE'RE GOING TO GIVE
EXAMPLES FROM OUR CHICAGO GROUP.
WE WANT TO EMPHASIZE THAT THIS
WAS A PANEL COLLABORATIVE
ACTIVITY AND WE'RE SPEAKING ON
BEHALF OF THE WHOLE CHICAGO SITE
WITH SPECIFICALLY ALSO ADVISOR
STAKEHOLDERS LISTED HERE ON THIS
SLIDE, AND NEXT SLIDE, PLEASE.
SO IF THIS WAS A LIVE
PRESENTATION, WE WOULD ALL BE
SITTING ON THE STAGE AS
PANELISTS WITH THE POT PLANT
POTTED PLANTNEXT TO US.
BUT THE VIRTUAL FOR MA'AM MADE
US TRUNCATE THE TIMING.
THEY WERE ALL CO-PREPARERS OF
THIS PRESENTATION.
THERE WERE MANY OTHER
STAKEHOLDERS WHO MADE IMPORTANT
CONTRIBUTIONS TO THE PROJECT BUT
THESE WERE THE FOUR WHO PREPARED
TODAY'S TALK.
WHAT I'D LIKE TO DO IS GIVE, IN
MY PART, THE HIGHLIGHTS ON THE
VALUE OF THE COMMUNITY ADVISORY
BOARD TO ACADEMIC RESEARCHERS
LIKE ME.
AND THAT THE -- AND THEN BRIDGET
REYNOLDS WILL GIVE THE
PERSPECTIVE OF THE STAKEHOLDER
ADVISORS.
SO FIRST IN THE PLANNING AND
DESIGN PHASE, EVEN IN THE GRANT
PREPARATION PART, PRECOVID, WE
LITERALLY HAD A LARGE GROUP OF
STAKEHOLDERS SEATED AT THE
CONFERENCE TABLE.
THIS PROVIDED MORE IMMEDIACY,
MORE SENSE OF PARTNERSHIP THAT
REALLY ENRICHED THE NUMBERS AND
THE DATA FROM NEEDS ASSESSMENT
AND FOCUS GROUPS, ALLOWING US TO
DO QUICK PIVOTS AND ADJUSTMENTS.
THEN AS WE WERE IMPLEMENTING
PROJECTS, A SUBGROUP OF THESE
STAKEHOLDERS REALLY CONTINUED IN
WEEKLY MEETINGS, WEEKLY
MEETINGS, WITH A LINE ITEM ON
THE AGENDA SAYING, HEY,
COMMUNITY ADVISORS, DO YOU HAVE
ANYTHING YOU WANT TO COMMENT ON
AND IT WAS JUST COMPLETELY OPEN,
WHATEVER THEY WISH TO BRING TO
THE AGENDA.
THEY HELPED AVOID SOME MISSTEPS
FOR RECRUITMENT TACTICS AND
DISSEMINATION, WHAT SUBURBS TO
GO TO MAYBE, WHAT KEY COMMUNITY
SITES TO GO TO FOR RECRUITMENT,
HOW TO ADJUST TO COVID, HOW TO
DISSEMINATE INFORMATION ON
SOCIAL MEDIA, OR EMAILS OR
FLYERS IN THE WAITING ROOM.
AND THEN FOR THE ANNUAL CHICAGO
SICKLE CELL SUMMIT, THEY REALLY
HELPED SET THE AGENDA AND
PRIORITIZE TOPICS AND THEN
TOWARD THE LAST TWO YEARS OF THE
SUMMIT, DID THE HEAVY LIFTING OF
THE ORGANIZATION OF IT AND
REALLY RUNNING THINGS.
AT THE NATIONAL LEVEL, COMMUNITY
STAKEHOLDER ADVISORS JOINED OUR
NATIONAL IN-PERSON SCDIC
MEETINGS IN BETHESDA, SAT IN
NATCHER CONFERENCE ROOM MEETING
ROOM SPEAKING ACTIVELY IN WORK
GROUPS, MADE STATEMENTS ABOUT
HOW RESEARCH SHOULD BE DONE ON
AGE 45 YEARS AND UP IN SICKLE
CELL DISEASE, EVEN THOUGH THE
SCDIC PROJECT WAS CUTTING THE
AGE LIMIT AT 45.
AND THEN JOINED IN BOTH THE
INFORMAL CONSENSUS AND THEN THE
FORMAL DELPHI CONSENSUS PROCESS
TO SET THE DEFINITION OF UP
AFFILIATED PATIENTS.
THEY WERE VERY IMPORTANT FOR
THAT.
AND SOME WENT ON TO REACH OTHER
PROGRAMS AND OTHER RESEARCH
PROJECTS.
THEN FINALLY THE SUSTAINABILITY
FOR THE FUTURE.
SO SUSTAINABILITY IS REALLY
IMPORTANT, IT'S NOT HAVING
ONE-OFF GRANT FUNDING FOR
COMMUNITY -- OR BUILD UP AND GET
DISSOLVED.
SUSTAINABILITY WILL MEAN USING
TOOLS OF IMPLEMENTATION SCIENCE
TO DEMONSTRATE THE IMPACT AND
HAVE A THEORETICAL FRAMEWORK
SUCH AS THE READINESS
FRAMEWORKS, SUSTAINABILITY
READINESS STRATEGY, WHICH IS AN
ADAPTATION OF THE IMPL IMPLEMENN
SCIENCE GETTING TO OUTCOMES THAT
WE'VE BEEN USING A LOT AT OUR
SITE IN CHICAGO.
FINALLY I WANT TO MENTION I'M
OLD ENOUGH TO REMEMBER THE NIH
COMPREHENSIVE SICKLE CELL
CENTERS WERE ALL REQUIRED TO
HAVE COMMUNITY INVOLVEMENT,
CONSIDERED ONE LEG OF THE
THREE-LEGGED STOOL REQUIRED
BUT -- CELEBRATE IMPLEMENTATION
SCIENCE IS BRINGING US TOOLS TO
MEASURE HOW COMMUNITY
STAKEHOLDER ADVISORS CONTRIBUTE
AND WE CAN REALLY KNOW HOW THEY
ARE INTEGRAL PARTNERS IN
RESEARCH IN SICKLE CELL DISEASE
AND OTHER TOPICS.
WITH THAT, I'M GOING TO HAND
OVER THE REST OF THE TIME TO
BRIDGET REYNOLDS.
>> HI.
THANK YOU FOR ALLOWING ME TO
SPEAK TODAY ON MY EXPERIENCES AS
A COMMUNITY ADVISORY BOARD
MEMBER.
AND I'D LIKE TO TALK ABOUT FIRST
OF ALL HOW DO YOU BECOME ONE,
WHAT DOES IT TAKE TO BECOME AN
ADVISOR, WHAT WERE THE
RESEARCHERS LOOKING FOR?
THEY WERE BEING LOOKING FOR
MEMBERS OF THE COMMUNITY FROM
ONE OR MORE HOSPITAL SITES, AND
IDEALLY THERE SHOULD BE NO
MAXIMUM AGE UNLESS IT'S CRITICAL
TO THE OUTCOME OF THE STUDY.
YOU SHOULD BE PROACTIVE.
YOU SHOULD WANT TO PARTNER IN
YOUR CARE AND HAVE A GENUINE
DESIRE TO ADVANCE THE SCIENCE.
AND THERE SHOULD BE A BIT OF
CURIOSITY ABOUT YOUR DISEASE AND
HOW IT AFFECTS YOU.
AND THAT SHOULD EXTEND BEYOND
YOURSELF TO OTHERS, REQUIRING A
BIT OF ALTRUISM.
AND FINALLY, YOU SHOULD HAVE
GOOD COMMUNICATION SKILLS.
YOU SHOULD BE OBJECTIVE AND COME
FROM A SINCERE PLACE.
WHAT DO WE DO?
WELL, WE PLAN AND HOST THE
ANNUAL CHICAGO SICKLE CELL
SUMMIT.
WE PARTICIPATE IN WEEKLY ISAAC
MEETINGS.
WE PARTICIPATE IN QUARTERLY
COMMUNITY ADVISORY BOARD
MEETINGS.
AND IN SCDIC WORK GROUPS ON THE
THREE INTERVENTIONS: ALIGN,
MESH AND UNAFFILIATED PATIENTS.
AND WE FORM OUR OWN ISAAC WORK
GROUPS.
WE -- SUCH AS WHEN WE PLANNED A
SUMMIT.
AND WE SURVEY THE SICKLE CELL
COMMUNITY, MAYBE FOR SOMETHING
WE NEED TO KNOW OR AT THE BEHEST
OF RESEARCHERS.
AND WHO MAY WANT A BROADER
PERSPECTIVE ON SOMETHING.
AND THEN WE MAY DRAFT POSITION
STATEMENTS.
IF THERE'S SOMETHING THAT WE
FEEL NEEDS ATTENTION, WE WILL DO
A POSITION STATEMENT ON THAT,
AND THEN WE CAN PUSH THAT UP TO
NIH.
WE SELECT ONE PERSON FROM THE
ADVISORY BOARD TO REPRESENT US
AT THE ANNUAL NIH MEETINGS.
AND THERE, YOU ARE NOT JUST A
PASSIVE PARTICIPANT, BUT YOU CAN
ACTIVELY PARTICIPATE AND HAVE
INPUT WHICH WILL BE HEARD.
IT'S VERY ACTIONABLE.
AND THAT PERSON WILL COME BACK
AND UPDATE US ON THE PROCEEDINGS
OF THAT NEEDING. MEETING.
>> THIS IS ROBERT.
I JUST WANT TO GIVE YOU A
2-MINUTE WARNING.
>> OKAY.
EMPOWERMENT.
WHY BE INVOLVED?
BECAUSE YOU WANT TO -- WE WANT
TO HAVE EQUITY, SKIN IN THE
GAME, WE WANT TO BUILD TRUST
BETWEEN THE PEOPLE WHO ARE
STUDYING US AND WHO ARE
PROVIDING CARE DESIGN FOR US.
THERE IS BIDIRECTIONAL TRUST.
WE KNOW THE RESEARCHERS, WE KNOW
THE TEAM AND THEY KNOW US.
WE WANT TO CONTRIBUTE AND
PARTNER SOLUTIONS, PROVIDE REAL
LIFE EXPERIENCES AND
PERSPECTIVES THAT WILL KEEP THAT
RESEARCH RELEVANT FOR THE
RESEARCHER AND THE SICKLE CELL
COMMUNITY.
AND THERE ARE PERKS.
ACCOMPLISHMENT, CAMARADERIE,
TEAM WORK, A SENSE OF PURPOSE
THAT IS BOOSTED BY YOUR ABILITY
TO INFLUENCE THE AGENDA ON THE
LOCAL AND THE NATIONAL LEVEL.
AND WHAT'S MORE, YOU ARE
LEARNING FROM A DIVERSE GROUP OF
PROFESSIONALS, AND SOME OF YOUR
PEERS ARE PROFESSIONALS TOO, AND
IMPLEMENTATION SCIENCE,
SCIENTISTS, TRANSLATIONAL
SCIENTISTS AND THE LOT.
YOU HAVE A SEAT AT THE TABLE,
AND A REAL SENSE OF BELONGING.
AND FINALLY, THESE ARE SOME OF
MY PEERS ON THE ADVISORY BOARD,
AND I'D LIKE -- THESE ARE SOME
QUOTE FROM MY PEERS.
AND MAXCINE SAYS SHE LOOKS
FORWARD TO WORKING ON MORE
PROJECTS AND FINDING WAYS TO
HELP IMPROVE THE HEALTH OF THE
SICKLE CELL COMMUNITY.
BEVERLY SAYS THE OPPORTUNITY HAS
EMPOWERED HER AND HAS GIVEN HER
A SENSE OF BELONGING WORKING
WITH THE RESEARCH TEAM AT THE
LOCAL AND NATIONAL LEVELS.
AND FINALLY, DORINDA SAYS THAT
HER VOICE AND THAT OF OTHER
INDIVIDUALS WITH SICKLE CELL IS
WELCOMED, HEARD AND VALUED.
AND THANK YOU SO MUCH FOR YOUR
TIME, AND I'D LIKE TO OPEN THIS
UP TO OUR PANEL TO ANSWER
QUESTIONS.
DO WE HAVE ANY QUESTIONS?
>> I DON'T SEE ANY QUESTIONS IN
THE QUEUE.
YOU MAY JUST CHECK, I THINK
THERE'S SOME ROLLING THINGS IN
THE CHAT.
BUT WE'VE RUN OUT OF TIME FOR
THIS SESSION.
SO IT'S TIME TO MOVE ON TO THE
NEXT ONE.
IF YOU CAN BRING UP THE SLIDES
FOR THE LIFETIME NARRATIVE.
THANK YOU.
THIS PROJECT AS YOU CAN SEE IS
ONE OF THE PROJECTS THAT WERE
DONE BY THE SCDIC AND WE ARE IN
THE PROCESS OF COMPLETING THE
ANALYSIS.
SO THIS IS A QUALITATIVE
PROJECT.
IT GREW OUT OF OUR DISCUSSIONS
ABOUT WHAT IS UNAFFILIATION, AND
WHAT DOES IT MEAN TO PEOPLE TO
NOT BE ENGAGED IN CARE VERSUS
ENGAGED IN CARE.
WE REALLY COULDN'T ANSWER THIS
FROM THE INDIVIDUAL WITH SICKLE
CELL DISEASE'S PERSPECTIVE, SO
WE DEVELOPED A RESEARCH
QUESTION, HOW DO PARTICIPANTS,
PATIENTS WITH SICKLE CELL
DISEASE, UNDERSTAND OR VIEW
THEIR ENGAGEMENT IN MEDICAL CARE
AND FREETM TREATMENT FOR THEIR ?
AND THAT IS WHAT GUIDED OUR
RESEARCH.
SO OUR METHODS.
I'M REVIEWING THIS VERY QUICKLY,
IF PEOPLE HAVE QUESTION,
SPECIFIC QUESTIONS, I CAN FOLLOW
UP ON THE CHAT.
WE USED A NARRATIVE APPROACH
WITH A TWO-STEP INTERVIEW
SCHEDULE, AND WE ASKED THE
PARTICIPANTS TO RECOUNT THEIR
TREATMENT HISTORY WITH A FOCUS
ON THEIR CHANGING ENGAGEMENT IN
CARE.
WE ALSO ASKED PARTICIPANTS, AND
YOU CAN SEE ON THE RIGHT-HAND
SIDE OF THE SCREEN, WE CREATED A
TABLE OR A LOG OF EVENTS, AND WE
USED -- WE HAD THE PARTICIPANTS
HELP US CREATE THIS JOINTLY OR
TO RATIFY ONE OF THESE TABLES IF
WE CREATED IT, AND THEN ALSO TO
SORT OF RATE THESE EVENTS TO
BEING POSITIVE, NEGATIVE OR
NEUTRAL.
INTERVIEWERS WERE TRAINED AT
EACH SITE.
INTERVIEWS WERE CONDUCTED
LOCALLY, TRAN SCRIBED AND TRANSD
UPLOADED TO A 1 CENTRAL
REPOSITORY.
I'M GOING TO GO THROUGH THIS
QUICKLY BECAUSE I DON'T WANT TO
RUN OUT OF TIME.
HERE YOU CAN READ OUR
RECRUITMENT METHODS OF HOW WE
FOUND PEOPLE WHO MET THE
DEFINITION OF UNAFFILIATED.
AND THEN OUR INCLUSION CRITERIA,
THESE ARE PEOPLE OVER THE AGE OF
18, THEY HAD A VERIFIED
DIAGNOSIS OF SCD, WHICH WE
DEVELOPED AS PART OF THE -- OR
MET AS PART OF THE INTERVIEW
PROCESS.
THEY MET THE DEFINITION OF
UNAFFILIATED FROM THE DELPHI
STUDY.
AND YOU CAN SEE THE DEFINITION
BELOW.
SO OUR ANALYSIS PROCESS.
A NARRATIVE APPROACH FOCUSES ON
THE STORIES THAT PARTICIPANTS
TELL DURING THE INTERVIEWS.
THIS IS A LITTLE DIFFERENT FROM
OTHER QUALITATIVE APPROACHES.
SO THE ANALYSIS ATTENDS TO THE
PARTICIPANTS' ACTION IN THE
STORY, STORY OUTCOMES, YOU CAN
PLOT -- YOU CAN SORT OF PLOT OR
GRAPH PLOT LINES OR LOOK AT
CHARACTERIZATIONS, SO IT'S A
LITTLE BIT DIFFERENT FROM
REGULAR QUALITATIVE WORK.
THE DATA COLLECTION IS RICH AND
COMPLEX, AND TODAY BUT WE'RE
ONLY GOING TO SHARE JUST A
LITTLE BIT OF THIS DATA, AND
THIS IS A PARTICIPANT'S
RATIONALE IN COMING AND GOING
FROM CARE.
IN ADDITION TO THE NARRATIVE
ANALYSIS THAT WE'RE CURRENTLY
COMPLETING, WE ALSO COMPLETED A
RAPID QUALITATIVE ANALYSIS OF
THE TRANSCRIPTS, AND THAT
INFORMATION HAS ALSO INFORMED
WHAT WE PRESENT TODAY.
SO THESE WERE OUR PARTICIPANTS.
YOU CAN SEE THESE WERE FROM SIX
OF THE EIGHT SITES THAT WERE
PARTICIPATING IN THE SCDIC
CONSORTIUM.
SO OUR PRIMARY FINDINGS.
THE DATA ANALYSIS IS IN PROCESS,
AND WE ARE SHARING PRELIMINARY
RESULTS.
AND I WANT TO TAKE A MOMENT,
WHENEVER YOU'RE DOING
QUALITATIVE WORK, IT'S ALWAYS
VERY IMPORTANT TO SORT OF ENGAGE
IN A CERTAIN AMOUNT OF
INVESTIGATOR REFLEXIVITY.
SO WHEN WE BEGAN THIS PROCESS,
THERE WERE ASSUMPTIONS WE MADE
THAT ULTIMATELY HAVE BECOME
CHALLENGED AS WE DID THIS.
SO ONE OF THE ASSUMPTIONS THAT
WE MADE WAS THAT PATIENTS ARE
GOING TO VIEW THEIR ILLNESS
PROCESS IN THE SAME WAY OR A
SIMILAR WAY THAT PROVIDERS DO.
THE IDEA OF BEING ENGAGED IN
CARE OR NOT ENGAGED IN CARE.
AND AS WE LISTEN TO THE STORIES
OF PARTICIPANTS, THEY HAD A VERY
DIFFERENT -- THEY HAD A
DIFFERENT UNDERSTANDING, AND
I'LL TALK A LITTLE BIT ABOUT
THAT.
AND SO SOME OF OUR ASSUMPTIONS
WERE ACTUALLY CHALLENGED BY OUR
PARTICIPANTS.
AND THE OTHER IDEA THAT WE
STARTED WITH WAS THAT A LIFE
NARRATIVE WOULD CAPTURE THE
ILLNESS EXPERIENCE AND THE
REASONS FOR ENGAGING AND NOT --
AND FOR LEAVING CARE, AND AS
WE'VE DONE THE ANALYSIS, WE ARE
REFLECTING THAT POSSIBLY AN
ILLNESS NARRATIVE THAT WE
THOUGHT WOULD BE INFORMATIVE MAY
NOT HAVE BEEN THE BEST WAY TO
CAPTURE THIS DATA, BUT WE THINK
NONETHELESS WE'VE GOTTEN SOME
VERY INTERESTING RESULTS.
SO THE PATIENTS' PERSPECTIVE,
THE REASONS FOR NOT BEING IN
CARE.
SO THESE ARE QUOTES OR
ABSTRACTIONS OF QUOTES.
SO WHAT WE FOUND WAS THAT
OFTENTIMES INDIVIDUALS HAD
BREAKS IN CARE, AND THEY
DESCRIBE MOVING, GOING TO
COLLEGE, GETTING A NEW JOB, AND
THAT PARTICIPANTS MADE CHOICES
AFTER NOT -- MADE CHOICES
FOLLOWING THESE BREAKS IN CARE
NOT TO RE-ENGAGE OR TO FOLLOW UP
IN REFERRALS.
AND WHAT'S HIGHLIGHTED THERE IN
YELLOW IS THIS IS SOME OF OUR
REFLECTION OF THE ANALYSIS
PROCESS, EITHER WHERE WE ARE
SHARING WITH YOU OUR SYNTHESIS
OR WHERE WE'RE STILL DEBATING AS
INVESTIGATORS.
FLIESH SO HERE TSO HERE THERE'SN
INFERENCE THAT ABSENCE OF THE
PEOPLE -- WITHOUT THE SICKLE
CELL DISEASE COMMUNITY OR
PERSONAL CONNECTIONS WITH
PROVIDERS, THAT THIS SEEMED TO
GET IN THE WAY OF CONNECTIVITY.
SO WHEN PEOPLE LEFT AND WENT
SOMEWHERE, THEY DIDN'T HAVE
THESE COMMUNITY AND PERSONAL
SUPPORTS OR CONNECTIONS, AND
THAT SEEMED TO FOSTER PEOPLE NOT
GOING BACK INTO CARE.
THERE WASN'T A PROMPT.
PEOPLE ALSO HAD DIFFICULTY
GETTING OUTPATIENT AND CLINIC
APPOINTMENTS, AND SCHEDULING WAS
MENTIONED VERY FREQUENTLY, THE
IDEA THAT MANY OF OUR INTERVIEW
SUBJECTS WERE YOUNG ADULTS, MOST
IF NOT ALL OF THEM ARE WORKING.
IT IS VERY HARD TO FIND CLINIC
TIMES THAT ARE NOT OVERLAPPING
WITH WORK TIME.
AND THAT WAS AN IMPORTANT
DISCUSSION POINT.
INDIVIDUALS ALSO HAD
MISINFORMATION, AND THIS
MISINFORMATION LED THEM NOT TO
SEEK CARE ONCE THEY LEFT CARE.
SO THIS WAS AN EXTREME EXAMPLE,
BUT ONE OF OUR RESPONDENTS SAID
IN THEIR FAMILY, ONLY MEN CAN
GET SICKLE CELL DISEASE AND THAT
WOMEN DIDN'T GET SICKLE CELL
DISEASE.
AND YOU KNOW, THIS IS LATER
DISPELLED BUT THE BELIEF
WASHINGS AS A YOUNG WOMAN, I
DON'T NEED TO GET CARE BECAUSE
SICKLE CELL DISEASE DOESN'T
AFFECT WOMEN.
TRANSPORTATION FOR NON-ACUTE
CARE VISIT TREATMENTS WAS ALSO
VERY IMPORTANT.
ONE OF THE PARTICIPANTS SAID I
WENT OUT THERE A COUPLE OF TIMES
BUT I DIDN'T KEEP UP WITH THE
GOING BACK AND FORTH BECAUSE I
DIDN'T HAVE TRANSPORTATION.
TRANSPORTATION FOR ACUTE CARE
WAS NOT MENTIONED AS A PROBLEM.
BUT FOR ONGOING AND CHRONIC
CARE, IT WAS A DIFFICULTY.
AND THEN INSURANCE FOR
PREVENTIVE OR ONGOING CARE WAS
ALSO A REASON FOR NOT BEING IN
CARE.
AND I HAVE TO MOVE REALLY
QUICKLY.
WE HAD THIS IDEA OF PEOPLE
HAVING A SENSE OF AGENCY, I CAN
CONTROL IT, IT DOESN'T CONTROL
ME.
AND SO PEOPLE WERE MANAGING
THEIR SYMPTOMS OUTSIDE OF THE
MEDICAL ENVIRONMENT.
THEY DIDN'T FEEL THEY NEEDED
INPATIENT CARE.
AND YOU CAN LOOK VERY QUICKLY AT
SOME OF THESE BECAUSE I'VE JUST
ABOUT RUN OUT OF TIME, AND I
WANT TO BE A GOOD STEWARD.
BUT AGENCY WAS IMPORTANT.
WHY PEOPLE RETURN TO CARE.
THE BIG EXPLANATION WAS I GOT
SICK.
I GOT SICK AND I HAD TO, PEOPLE
WERE HAVING MORE ED VISITS AND
THEY FELT THERE WAS A NEED TO
RE-ENGAGE IN CHRONIC CARE.
AND THEN -- AS PEOPLE FELT THEY
WERE GETTING SICKER, THEY WERE
RE-ENGAGING IN ONGOING CARE.
MORE EXAMPLES ABOUT THAT IT WAS
TIME.
PEOPLE WERE GETTING OLDER, THEY
WERE SENSING MORE DISEASE IN
THEIR BODIES.
THEY HAD ADDITIONAL CHRONIC
ILLNESSES THAT OVERLAPPED THEIR
SICKLE CELL DISEASE, OR SOME
PEOPLE JUST FELT THIS IT HAD
BEEN A LONG TIME AND THEY FELT
IT WAS TIME TO GET BACK INTO
CARE.
SO WHEN YOU DO QUALITATIVE WORK,
IT'S ALSO IMPORTANT TO THINK
ABOUT WHAT YOU DIDN'T HEAR, AND
SOMETIMES THIS IS RELATED TO THE
QUESTIONS YOU ASKED, BUT
SOMETIMES THIS IS ALSO ABOUT
WHAT IS NOT IMPORTANT TO PEOPLE.
SO WE DID NOT HEAR ANY COMMENTS
ABOUT TRADITIONAL PEDS TO ADULT
TRANSITION.
THAT WASN'T IDENTIFIED AS A
PROBLEM.
ALTHOUGH PEOPLE DID TALK ABOUT
HOW LIFE CHANGES CO-OCCUR WITH
ENGAGEMENT AND DISENGAGEMENT.
THIS IS A PLACE WHERE THE
ANALYSIS TEAM IS CONTINUING TO
DEBATE AT THIS POINT.
INSURANCE OR COSTS WERE NOT
IDENTIFIED AS A BARRIER FOR
ACUTE CARE BUT WERE MENTIONED
FOR OBTAINING ONGOING CARE.
PEOPLE DID NOT EXPRESS THE NEED
TO WORK WITH HEALTHCARE
PROVIDERS FOR DAY TO DAY DISEASE
CARE MANAGEMENT.
AND THE USE OF SICKLE CELL
DISEASE MEDICATIONS AS A
MODIFYING THERAPY WAS NOT RAISED
AS AN ISSUE.
>> 2 MINUTE WARNING.
>> THANK YOU.
SO OUR PRELIMINARY CONCLUSIONS.
MY SICKLE CELL DISEASE IS NOT A
CONSTANT THING.
I'M NOT CONSTANTLY SICK SO IT'S
LIKE I CAN -- I FEEL OKAY, I
DON'T NEED TO GO TO THE HOSPITAL
ALL THE TIME BECAUSE I'M NOT
SICK ALL THE TIME.
THAT WAS SOMETHING THAT WAS
VERBALIZED BY MANY OF THESE
YOUNG ADULTS.
SO THE ANALYSIS CONTINUES BUT
THESE ARE OUR PRELIMINARY
THOUGHTS.
UNAFFILIATED PARTICIPANTS
RELAYED THEIR CARE STORIES AS
EPISODES OF ILLNESS.
OFTEN OF ACUTE ILLNESS.
AND THEN INTERVALS OF HEALTH.
AND THERE WAS AN ABSENCE OF THE
NEED FOR CARE IN THE WAY THEY
DESCRIBED THESE STORIES.
OTHERS THOUGHT THAT THE
PARTICIPANTS DID VIEW THEIR
ILLNESS AS CHRONIC, BUT THAT THE
HEALTHCARE SYSTEM WAS NOT ALWAYS
HELPFUL, AND THIS LED TO
INTERRUPTIONS IN CARE.
AND THIS IS ONE OF THE POINT
THAT WE'RE WORKING OUT IN OUR
STORIES.
PARTICIPANTS DID NOT LINK CARE
EPISODES TO CREATE LARGER
NARRATIVES.
AND WE ARE GOING BACK AND
EXPLORING, IS THIS EPISODIC
UNDERSTANDING OF CARE THE WAY WE
ASK QUESTIONS, OR IS THIS TRULY
THE WAY INDIVIDUALS THAT ARE
UNAFFILIATED ARE SEEING THEIR
CARE?
BEING IN AND OUT OF CARE WAS
PRIMARILY OR OFTEN AN ISSUE OF
CHOICE FOR THESE YOUNG ADULTS.
INDIVIDUALS DISENGAGED CARE AS A
RESULT OF LIFE EVENTS, BUT THEY
DID NOT FEEL THE NECESSITY TO
RE-ENGAGE IN CARE AFTER THEY
WERE RE-SETTLED OR AFTER THESE
CHANGES.
SO I ACTUALLY HAVE RUN OUT OF
TIME AND I WANT TO BE A GOOD
STEWARD HERE.
YOU CAN READ THESE QUICKLY AND
LET'S GO ON TO THE NEXT SLIDE.
SO THESE ARE OUR LIMITATIONS.
AND THIS IS VERY IMPORTANT TO
THINK ABOUT AS WE FURTHER
ANALYZE OUR DATA AND AS PEOPLE
LOOK AT WHAT WE WERE DOING.
IMPORTANT TO POINT OUT, WE SPOKE
ONLY WITH OR PRIMARILY WITH
YOUNG ADULTS, THAT WAS A
CONSTRAINT OF THE CONSORTIUM.
WE'VE NOT DONE OR LOOKED AT
THESE MATERIALS BY GENDER.
AND IT WAS VERY INTERESTING IN
OUR ANALYSIS THAT THE IDEA OF
HOSPITAL AS A LOCATION FOR ACUTE
CARE BUT ALSO THAT WAS THE PLACE
WHERE ONGOING CARE, THAT TERM
WAS USED IN SORT OF THINKING
ABOUT GOING TO A CLIPPING OR
A CLINIC OR ADOCTOR'S OSS
DOCTOR'S OFFICE.
THOSE TWO ARE OFTEN CONFLATED
AND WE OFTEN HAVE TO TEASE THOSE
OUT.
I'M GOING TO END HERE AND
INTRODUCE OUR NEXT SPEAKER.
DR. JANE HANKINS.
I WANT TO CORRECT THE FACT THAT
I ERRED IN SAYING JANE'S NAME
EARLIER.
IT IS DR. HANKINS.
AND SHE'LL TALK TO US ABOUT THE
MESH STUDY.
>> THANK YOU, DR. GIBSON.
YEAH, HAWKINS IS MY COUSIN.
I'M HANKINS.
WE'LL DISCUSS THE DETERMINANTS
OF HYDROXYUREA ADHERENCE IN A
STUDY CALLED MESH.
I WANT TO BEGIN BY REVIEWING
WHAT THE CURRENT DEFINITION OF
ADHERENCE IS.
WHICH IS TH THE EXTENT TO WHICHA
PERSON'S BEHAVIOR OF TAKING A
MEDICATION AGREES WITH THE
RECOMMENDATIONS FROM THAT
HEALTHCARE PROVIDER.
AND THAT PUTS THE EMPHASIS ON
THE PATIENT'S AUTONOMY AND THE
RELATIONSHIP WITH THE PROVIDER,
AS OPPOSED TO THE DEFINITION OF
COMPLIANCE, WHICH IS A
UNIDIRECTIONAL RELATIONSHIP.
SO IN A LARGE EVALUATION OF
PATIENTS USING MEDICAID CLAIMS
DATA, LESS THAN HALF OF THE
PATIENTS WERE PRESCRIBED
HYDROXYUREA AND OF THOSE,
APPROXIMATELY A THIRD HAD
APPROPRIATE ADHERENCE.
SO JUST BY LOOKING AT THE LEVEL
OF BARRIERS HERE, YOU CAN EASILY
TELL THAT IT'S NOT ONLY PATIENT
LEVEL BARRIERS THAT IMPAIRS USE
OF HYDROXYUREA BUT THE SYSTEM
AND PROVIDER-LEVEL BARRIERS.
SO HERE WHAT I'M SHOWING YOU IS
AN INTERVENTION MAPPING MODEL
WHICH IS AN IMPLEMENTATION
SCIENCE METHOD TO DEVELOP NEW
INTERVENTIONS.
HERE IN THE SHADED AREA, I'M
SHOWING YOU THE DETERMINANTS OF
MEDICATION ADHERENCE
SPECIFICALLY TO HYDROXYUREA THAT
WE IDENTIFIED THROUGH OUR OWN
DATA.
WE DID QUANTITATIVE AND
QUALITATIVE DATA ANALYSIS AND
LITERATURE REVIEW, AND WE
IDENTIFIED THE SALIENT
DETERMINANTS OF WHAT GETS IN THE
WAY OR BARRIERS TO TAKING
HYDROXYUREA IN A SICKLE CELL
POPULATION.
SO FOR EXAMPLE, FORGETFULNESS,
HEALTH EFFICACY, KNOWLEDGE, WHEN
THEY ARE LOW, THEY IMPAIR THE
USE AT THE PATIENT LEVEL.
AT THE PROVIDER LEVEL, WE
IDENTIFIED SELF-EFFICACY AND
COGNITIVE KNOWLEDGE OF
HYDROXYUREA AS BARRIERS FOR
PROVIDERS.
SO WE DEVELOPED INTERVENTIONS
THAT DIRECTLY TARGET THOSE
DETERMINANTS THAT WE IDENTIFIED
AS SALIENT IN GETTING IN THE WAY
OF UTILIZATION AND WE DID THAT
FOR THE PROVIDER BARRIERS AND
THE PATIENT BARRIERS.
SO HERE ARE EXAMPLES OF
BARRIERS.
WE PACKAGED ALL THE
INTERVENTIONS IN A MOBILE HEALTH
APPLICATION OR AN APP.
SO ALL THESE INTERVENTIONS WENT
INTO AN APP FOR THE PATIENTS
WITH A PATIENT APP CALLED IN
CHARGE HEALTH AND PROVIDERS' APP
WAS CALLED HU2 BOX DEVELOPED BY
DR. SHAH FROM DUKE.
SO INTERVENTIONS ACT ON
DETERMINANTS THAT WILL LEAD TO
CHANGES IN THE PERFORMANCE
OUTCOMES THAT AT THE END OF THE
DAY IMPROVE ADHERENCE AND
IMPROVE QUALITY OF LIFE.
THESE TWO APPS, THESE TWO
COMBINED MULTILEVEL
INTERVENTIONS HATCHED INTO TWO
DIFFERENT APPS ARE BEING USED
TOGETHER IN THE STUDY CALLED
MESH, INTEGRATION OF MOBILE
HEALTH INTO SICKLE CELL DISEASE
CARE TO INCREASE HYDROXYUREA
UTILIZATION AS MENTIONED BY
DR. GIBSON IN THE PRIOR -- IN
THE FIRST TALK.
AND A WE'RE MEASURING ADHERENCEF
PROPORTION OF DAYS COVERED OR
PDC WHICH IS A SURROGATE OF
MEDICATION ADHERENCE.
IT'S A SURROGATE AND ACCEPTED
OUTCOME FOR -- END POINT FOR
ADHERENCE.
THESE ARE THE SEVEN SITES FROM
THE SCDIC THAT ARE PARTICIPATING
IN THE STUDY.
WE'VE ENROLLED A TOTAL OF
293 PATIENTS AGE 15 TO 45 NEW TO
HYDROXYUREA OR ON CHRONIC USE OF
HYDROXYUREA, AND 89 PROVIDERS
WHO HAD AT LEAST ONE PATIENT
WITH SICKLE CELL DISEASE UNDER
THEIR CARE FOR THE FOLLOWING 12
MONTHS AFTER ENROLLMENT.
AND WE WANTED TO LOOK AT WHAT
WERE THE DRIVERS OF ADHERENCE IN
THE STUDY TO SEE IF THEY
CONCURRED WITH THE LITERATURE IN
OUR PRIOR ANALYSIS AND IF WE
IDENTIFIED NEW TARGETS OR NEW
PREDICTORS OF ADHERENCE IN THIS
GROUP.
SO WE DID A BASELINE ANALYSIS
BEFORE THEY STARTED USING THE
APP, THE PATIENTS, AND FOR
PATIENT LEVEL PREDICTORS, WE
USED A NUMB WE ARE OF NUMBER OF,
COGNITIVE DEPRESSION SYMPTOMS,
AMONG THE CLINIC LEVEL
PREDICTORS WE LOOKED AT THE TYPE
OF PROVIDER IN THE CLINIC, THE
TYPE OF CLINIC, AND FOR THE
PROVIDERS, THEIR SELF-EFFICACY,
THEIR COMFORT IN MANAGING
HYDROXYUREA AND THEIR KNOWLEDGE
IN MANAGING HYDROXYUREA.
OF THE 293 PATIENTS ENROLLED,
270 PATIENTS HAD ONE HYDROXYUREA
REFILL IN THE SIX MONTHS PRIOR
TO THE ENROLLMENT THAT
CONSTITUTED THE BASELINE PERIOD
SIX MONTHS BEFORE THE ENROLLMENT
IN THE STUDY.
SO WE INCLUDED THOSE
270 PATIENTS IN THE BASELINE
ANALYSIS OF PREDICTORS OF
ADHERENCE TO HYDROXYUREA.
THE OTHER PATIENTS WERE NEW TO
THE TREATMENT OR THEY DIDN'T
HAVE A DOCUMENTED REFILL OF MORE
THAN SIX MONTHS FROM ENROLLMENT.
THE BASELINE ADHERENCE FOR THE
270 PATIENTS IN THIS ANALYSIS IS
QUITE LOW.
EVEN LOWER THAN WE WERE
ANTICIPATING.
WE THOUGHT IT WAS GOING TO BE
AROUND 50%, WHICH IS WHAT THE
LITERATURE SAYS.
IT'S 42.6%, WITH A LITTLE BIT OF
VARIABILITY ACROSS THE
GENOTYPES, BUT NOT MUCH.
THE FACTORS AT THE PATIENT LEVEL
THAT WERE ASSOCIATED WITH HIGHER
ADHERENCE WERE HIGHER
SELF-REPORTED ADHERENCE,
PERCEIVED HYDROXYUREA EFFICACY,
HIGHER MEDICATION SELF-EFFICACY,
GREATER RELIANCE ON ON OTHERS AD
MORE COGNITIVE PROBLEMS,
PROBABLY BECAUSE THEY RECEIVED
GREATER ASSISTANCE.
THOSE FACTORS ASSOCIATED WITH
LOWER ADHERENCE WERE GREATER
FINANCIAL HARDSHIP, GREATER PAIN
INTERFERENCE AND POLYPHARMACY.
SO WHEN A PATIENT WAS USING AT
LEAST ONE MORE MEDICATION IN
ADDITION TO HYDROXYUREA.
THESE TWO GRAPHS SHOW THE NICE
RELATIONSHIP BETWEEN MEDICATION
SELF-EFFICACY ON THE LEFT, AND
THE ADHERENCE.
SO THE GREATER THE SELF-EFFICACY
OR THEIR BELIEF THAT THEY CAN
MANAGE THEIR TREATMENT, THE
BETTER THE ADHERENCE, AND THE
MORE -- THE GREATER NUMBER OF
MEDICATIONS, THE WORSE THEIR
ADHERENCE.
AND THE MULTIVARIABLE ANALYSIS,
THE FACTORS AT THE PATIENT LEVEL
THAT REMAIN SIGNIFICANT WERE
AGE, WHICH WAS CLOSE TO
SIGNIFICANCE, FINANCIAL
HARDSHIP, SELF-REPORTED
ADHERENCE, AND TAKING MORE THAN
ONE MEDICATION IN ADDITION TO
HYDROXYUREA.
AT THE CLINIC LEVEL FACTORS, THE
ONLY FACTOR THAT WAS SIGNIFICANT
WITH ADHERENCE WAS THE NUMBER OF
ADVANCED CARE PROVIDERS WHO WERE
ALSO ENROLLED IN THE STUDY.
SO THE MORE NURSE PRACTITIONERS
AND PHYSICIAN ASSISTANTS IN THE
CLINIC AS PART OF YOUR STAFF,
THE BETTER YOUR PATIENT'S
ADHERENCE.
THE SETTING OF THE CLINIC, URBAN
OR SUBURBAN, AND THE TYPE OF THE
CLINIC, ACADEMIC OR COMMUNITY,
WERE NOT ASSOCIATED WITH
INCREASED ADHERENCE.
WE ARE LOOKING CURRENTLY AT THE
PROVIDER LEVEL FACTORS.
WE'RE STILL DOING THE ANALYSIS,
BUT I CAN TELL YOU THAT THERE'S
VARIABILITY, SIGNIFICANT
VARIABILITY IN OUR SAMPLE IN
RELATION TO THE SELF-EFFICACY,
SO THE PROVIDER IS SAYING THEY
FEEL CONFIDENT AND THEY BELIEVE
THEY CAN MANAGE TREATMENT WITH
HYDROXYUREA IN SICKLE CELL
DISEASE, AND NOT A WHOLE LOT OF
DIFFERENCE BETWEEN PHYSICIANS
AND ADVANCED CARE PROVIDERS.
AS FAR AS KNOWLEDGE, WE HAD A
QUIZ ON WHAT WOULD YOU DO IN
THIS SCENARIO, WOULD YOU HOLD
THOSE IF THERE'S TOXICITY, HOW
DO YOU ESCALATE TO THOSE, AND
THE KNOWLEDGE WAS ALSO VARIED
BUT IN PHYSICIANS SCORING A
LITTLE BIT HIGHER THAN ADVANCED
CARE PROVIDERS.
A LOT OF THIS STUDY IS STILL
COMPLETING THAT ANALYSIS.
IETD LIKEI'D LIKE TO SHARE THE F
THE FIRST TWO SITES IN THE
STUDY.
WE HAD -- IT SO HAPPENED THOSE
TWO SITES STARTED ENROLLMENT
THREE MONTHS BEFORE THE COVID-19
PANDEMIC STARTED.
SO THE PATIENT WERE INVOLVED AT
THESE FIRST TWO SITES,
EXPERIENCED THE STUDY BEFORE THE
PANDEMIC AND DURING THE INITIAL
MONTHS OF THE PANDEMIC.
THE FIRST SITE HAD A LOCKDOWN IN
RESPONSE TO THE PANDEMIC THAT
LASTED TWO MONTHS AND WAS FASTER
TO START USING TELEHEALTH.
THE OTHER SITE HAD A LONGER
LOCKDOWN OF NINE MONTHS AND TOOK
LONGER FOR THE SITE TO BEGIN
USING TELEHEALTH.
SO THE SITE THAT HAD THE SHORTER
LOCKDOWN, THE PATIENT
EXPERIENCED IMPROVEMENT IN
ADHERENCE BOTH AT 3 AND 6 MONTHS
DURING THE STUDY, WHEREAS THE
SITE WITH THE LONGER LOCKDOWN,
THE PATIENTS EXPERIENCED A LOSS
OF ADHERENCE DURING THE STUDY.
HOWEVER, IN BOTH SITES, IF THE
PATIENTS USED THE APP, YOU SAW
AN INCREASE IN ADHERENCE, 40%
MORE IN RELATION TO THOSE WHO
DID NOT USE THE APP.
SO THIS GRAPH ON THE RIGHT
SHOWED THE CHANGE IN APP USE
AFTER THE START OF THE PANDEMIC
AND INCREASE IN THE PDC AND
THERE IS RELATIONSHIP, GREATER
AT HEERNS.
SO THIS IS BEGINNING OF EVIDENCE
IN OUR STUDY THAT THIS
INTERVENTION HELPED THE PATIENTS
IMPROVE ADHERENCE.
WITH THE QUALITATIVE ANALYSIS,
AND WE DID SAMPLING OF OUR
PATIENTS ACCORDING TO THE APP
USE, SO WE SAMPLED AMONG THOALS
WHO USE THE APP MORE AND THOSE
WHO USE THE APP LESS.
AND IN BOTH OF THOSE TWO SITES,
WITH THE SHORTER LOCKDOWN AND
LONGER LOCKDOWN, ALL THE
PATIENTS INTERVIEWED SAID THE
APP HELPED THEM TAKE THEIR HEAD
MEDALLIONCATION, TAKE THEIR
HYDROXYUREA.
HOWEVER, AMONG THE LOW USERS OF
THE APP, THEY DID STATE THAT THE
LOCKDOWN OR THE CONTACT WITH THE
PROVIDER WAS A BARRIER FOR THEM
TO BOTH USE -- TO OBTAIN THEIR
HYDROXYUREA AND REMAIN ON
TREATMENT.
AND MIXED METHOD ANALYSIS
IDENTIFIED THAT THE USE OF THE
APP WAS DEPENDENT ON THE
PATIENT-PROVIDER CONTACT.
SO IN CONCLUSION, THE
DETERMINANTS OF HYDROXYUREA
ADHERENCE OCCUR AT VARIOUS
LEVELS.
IT'S NOT ONLY CONSTRAINED TO THE
PATIENT LEVEL AS A BARRIER, AND
WE ARE STARTING TO IDENTIFY
POTENTIAL NEW TARGETS TO BOOST
ADHERENCE, SO POLYPHARMACY FOR
EXAMPLE, SO PATIENTS WHO TAKE
SEVERAL MEDICATIONS AND THIS IS
GOING TO BECOME MORE AND MORE OF
A FACTOR NOW THAT WE HAVE MORE
DISEASE MODIFYING THERAPIES THAT
WE'RE STARTING TO USE IN
COMBINATION WITH HYDROXYUREA,
AND THEN FINANCIAL HARDSHIP.
SO DEVELOPING INTERVENTIONS
THAT -- OR STRATEGIES THAT
TARGET FINANCIAL HARDSHIP AND
THINK ABOUT WAYS TO MITIGATE IT
AND IMPROVE ACCESS TO THE DRUG
IN POLYPHARMACY WILL BE HELPFUL
GOING FORWARD.
THEN THE CONTEXTUAL FACTORS WE
IDENTIFIED, CONTACT WITH
PROVIDERS WAS VERY IMPORTANT SO
WHATEVER INTERVENTION YOU GIVE,
YOU NEED TO BE MINDFUL THAT THE
CONTACT WITH PROVIDERS IS
IMPORTANT TO MAINTAIN THE USE OF
WHATEVER INTERVENTION WE
INTRODUCE.
WAND TO CONTAND TO CONTINUE THIE
STILL DOING A LOT OF ANALYSIS,
WE STILL HAVE THE OTHER SITES
STO ANSITES TOANALYZE BUT WE REH
BRIDGE GRANT TO FINISH ANALYSIS
TO PREPARE THE SUBMISSION TO
CONTINUE THE WORK THAT WE
STARTED.
SO THANK YOU, AND I'LL TURN IT
OVER TO DR. GIBSON.
THANK YOU.
>> THANK YOU VERY MUCH,
DR. HANKINS.
THE NEXT SPEAKER IS PAULA
TANABE, AND SHE'LL TALK ABOUT
THE ALIGN STUDY.
>> EXCELLENT.
THANK YOU, DR. GIBSON.
CAN I HAVE MY SLIDES, PLEASE?
PERFECT.
SO I WANT TO THANK NHLBI AND THE
CONSORTIUM FOR THIS OPPORTUNITY
TO PRESENT THE STATUS OF WHERE
WE ARE WITH THE ALIGN PROJECT
THAT WE'VE BEEN REFERRING TO A
LITTLE BIT.
AND DR. KING AND I FROM WASH-U
ARE LEADING THIS PROJECT WITH
THE ENTIRE CONSORTIUM AND THE
INVESTIGATORS AT EACH SITE.
SO ALIGN IS ACTUALLY -- STANDS
FOR AN INDIVIDUALIZED PAIN PLAN
WITH PATIENT AND PROVIDER ACCESS
FOR EMERGENCY DEPARTMENT CARE OF
SICKLE CELL DISEASE.
AND I THINK THE PATIENT ACCESS
IS WHAT IS VERY UNIQUE ABOUT
THIS PROJECT AND THE FIRST TIME
ANYTHING LIKE THIS ANYWHERE HAS
EVER BEEN DONE.
AND ALL EIGHT CENTERS FROM THE
CONSORTIUM ARE PARTICIPATING
HERE AGAIN, SO WE WANT TO THANK
ALL OF THE EMERGENCY PROVIDER,
HEMATOLOGISTS, SICKLE CELL
PROVIDERS, AND REALLY ALL OF THE
IT EXPERTS AT EACH CENTER AS
WELL, BECAUSE THIS PROJECT
REALLY IS CRITICAL TO HAVE ALL
OF THESE PARTNERS, EVERYBODY
REALLY HAS AN EQUAL PARTNER IN
MAKING THIS SUCCESSFUL.
AT EACH SITE.
SO THE PURPOSE OF ALIGN IS
REALLY TO IMPROVE THE CARE OF
EMERGENCY DEPARTMENT PATIENTS
WITH BOEs IN VOEs IN THE ED WHH
USUALLY IS MOST PEOPLE'S NUMBER
ONE COMPLAINT ABOUT ACCESS TO
SICKLE CELL DISEASE.
WE WANT TO -- THE UNIQUE PART IS
EMBEDDING INDIVIDUALIZED PAIN
PLANS INTO THE ELECTRONIC HEALTH
RECORD NOT ONLY FOR ED PROVIDERS
TO KNOW HOW TO TREAT INDIVIDUAL
PATIENTS, BUT FOR THE PATIENT TO
HAVE ACCESS TO THEIR INDIVIDUAL
PAIN PLAN IN THEIR OWN
ELECTRONIC HEALTH RECORD.
ONE OF THE RECOMMENDATIONS,
THERE ARE 17 RECOMMENDATIONS FOR
VOE IN THOSE GUIDELINES, AND ONE
WAS THAT PATIENTS SHOULD HAVE AN
INDIVIDUALIZED PAIN PLAN, SO FOR
EXAMPLE, THEY MAY NEED
10 MILLIGRAMS OF MORPHINE VERSUS
I MAY NEED 2 MILLIGRAMS OF
MORPHINE.
SO OUR PRIMARY OUTCOME FROM THIS
STUDY IS ACTUALLY THE PATIENT
SATISFACTION WITH THE ED QUALITY
OF CARE, WHICH I IS A VALIDATED
MEASURE.
WE HAVE MANY SECONDARY OUTCOMES
BUT ONE IS THE PROVIDER
CONFIDENCE, THE ED PROVIDER
CONFIDENCE IN MANAGING PAIN IN
THE ED.
OTHER SECONDARY OUTCOMES INCLUDE
UTILIZATION AND THEN ACTUAL
ADHERENCE TO THE IPP DURING THE
ED VISIT.
THESE OUTCOMES ARE ASSESSED AT
BASELINE AND THEN AFTER A
FOLLOW-UP ED VISIT IF THE
PATIENT HAS ONE.
PARTICIPANT INCLUSION CRITERIA
ARE SICKLE CELL DISEASE, AGAIN,
18 TO 45, SO ONLY ADULTS WHO HAD
TO HAVE ACCESS TO A SMARTPHONE,
AND VERY CRITICAL WAS THAT THEY
HAD TO HAVE ONE ED VISIT IN THE
PARTICIPATING SITE WITHIN THE
LAST 90 DAYS FROM ENROLLMENT,
AND THIS WAS THE VISIT THAT
PARTICIPANTS WERE ASKED TO RATE
THEIR BASELINE QUALITY OF CARE
SO IT WASN'T A BASELINE OF MY
OVERALL EXPERIENCE IN EMERGENCY
DEPARTMENTS BUT MY EXPERIENCE AT
THAT PARTICULAR SITE IN THE LAST
THREE MONTHS.
AND THEY ALSO HAD TO BE ENGAGED
IN CARE, IN OUTPATIENT CARE IN
THE SICKLE CELL CLINIC SO THAT A
SICKLE CELL PROVIDER COULD KNOW
THE PATIENT ENOUGH TO BE
CONFIDENT TO WRITE AN INDIVIDUAL
PLAN.
PROVIDER PARTICIPANTS WERE ANY
EMERGENCY PROVIDER WHO WORKED IN
THE STUDY ED, HAD ACCESS TO THE
EHR ROUTINELY, AND EACH SITE
DETERMINED REALLY WHO WOULD BE
THE RIGHT CATEGORY OF PROVIDER
THAT WOULD PROBABLY BE ORDERING
THAT FIRST DOSE.
AND THEN THE INCLUSION CRITERIA,
THEY ALSO HAD TO AGREE TO
PARTICIPATE IN FOLLOW-UP
SURVEYS.
A FEW PATIENTS WERE EXCLUDED BY
THE SICKLE CELL SPECIALISTS
BECAUSE THEY FELT THAT THAT
PARTICULAR PATIENT SHOULD NOT
HAVE A PROTOCOL OR SHOULD NOT BE
ADMINISTERED OPIOIDS IN THE ED.
AND THAT WAS DETERMINED BY THE
SICKLE CELL PROVIDER, NOT BY THE
ED PROVIDER.
SO THIS IS THE PROTOCOL HERE.
THESE ARE THE METHODS.
AND I CAN TELL YOU WHAT IT SAYS
ON THE LEFT.
IT LOOKS A LITTLE CUT OFF ON MY
SLIDE.
SO FIRST OF ALL PATIENTS HAD TO
GET ENROLLED AND CONSENTED AND
BEFORE COVID, IT WAS MOSTLY IN
THE CLINIC, DURING COVID IT ALSO
WAS VIA PHONE.
SO PATIENTS WERE IDENTIFIED.
THEY WOULD SIGN CONSENT AND THEN
THE SICKLE CELL PROVIDER WOULD
WRITE THE IPP FOR THAT PATIENT.
THEY WOULD DETERMINE WHAT DOSE
FOR VOE SHOULD BE IF THEY GO TO
THE EMERGENCY DEPARTMENT.
AND THEN AFTER THAT WAS WRITTEN,
THEN THE PATIENT AND PROVIDER
TALKED ABOUT THE PROTOCOL AND
THE RESEARCH STAFF MADE SURE
ALSO THAT THE PATIENT KNEW HOW
TO ACCESS THE PROTOCOL.
SO THIS WAS REALLY THE CRITICAL
PART, AND AT MANY SITES, THE
RESEARCH STAFF ACTUALLY WORKED
WITH THE PATIENT TO EITHER SIGN
THEM UP FOR THEIR ELECTRONIC
PORTAL OR MAKE SURE THAT THEY
KNEW HOW -- AND MAKE SURE THEY
KNEW HOW TO ACCESS IT.
SO ALL PATIENTS WERE GIVEN A
WALLET CARD.
NOW THE WALLET CARD WAS NOT LIKE
IN THE PAST, WHERE PATIENTS WERE
MAYBE GIVEN A LETTER THAT THEY
WOULD GIVE TO THE ED PROVIDER TO
SAY, HEY, HERE IS MY DOSE.
THAT JUST HISTORICALLY HAS BEEN
VERY UNSUCCESSFUL.
FOR A LOT OF DIFFERENT REASONS.
PROVIDERS WANT TO SEE SOMETHING
IN THE EHR TO BE BELIEVABLE.
SO THE WALLET CARD IS THE
INSTRUCTIONS FOR THE PATIENT ON
HOW THEY CAN GO IN TO THEIR
PATIENT PORTAL ELECTRONIC HEALTH
RECORD AND FIND THEIR IPP.
MANY OF THE SITES THAT USE EPIC
FOR EXAMPLE USE THE
COMMUNICATIONS TAB SO THE
PATIENT WOULD SIGN IN TO THEIR
PORTAL, GO TO COMMUNICATIONS AND
LOOK FOR A LETTER AND THAT'S
WHERE THE IPP WAS WRITTEN.
SO THIS ALLOWED THE PATIENT
THEN, DURING FUTURE ED VISITS,
TO PULL THAT UP AND SHOW TO THE
ED PROVIDER, WHERE IT LOOKS VERY
REAL BECAUSE IT IS VERY REAL, IT
IS IN THEIR ELECTRONIC HEALTH
RECORD.
AND THIS REALLY GETS AT ONE OF
THE LONG-TIME BARRIERS FOR
TREATING PATIENTS WITH SICKLE
CELL IN THE EMERGENCY
DEPARTMENT.
AND THAT IS THAT THEY ARE NOT
BELIEVED AND THEY'RE JUST
ASSUMED TO BE SEEKING DRUGS FOR
ADDICTION VERSUS SEEKING DRUGS
FOR PAIN, WHICH THEY ARE.
THEY WERE ALSO GIVEN SOME
TALKING POINTS ABOUT HOW TO TALK
WITH THE PROVIDER ABOUT THIS.
THE ED PROVIDERS ALSO RECEIVED
EDUCATION ABOUT THE PROTOCOL,
RECEIVED EDUCATION ABOUT WHERE
THEY CAN FIND THE PROTOCOL IN
THE ELECTRONIC HEALTH RECORD
FROM THEIR VIEW AS WELL.
SO THEN THIS IS ONE OF THOSE
REALLY TRICKY PROTOCOLS BECAUSE
YOU CAN'T PREDICT WHEN PATIENTS
ARE GOING TO COME IN WITH A VOE.
SO WE ENROLLED A LOT OF
PATIENTS, WE OVERENROLL
PATIENTS, AND THEN WAIT FOR THEM
TO HAVE AN ED VISIT.
IN THIS PARTICULAR PROJECT,
RESEARCH STAFF WOULD MONITOR
THEN FOR ED VISITS, AND THEN
AFTER THE PATIENT HAD AN ED
VISIT, THERE WAS REALLY NO
INTERVENTION IN THE EMERGENCY
DEPARTMENT AT ALL.
AFTER THAT VISIT, THE RESEARCH
STAFF WOULD SEND THE SAME SURVEY
OUT ABOUT THEIR QUALITY OF CARE
WITHIN 96 HOURS ABOUT THAT
VISIT, AND THEN THE PROVIDER WHO
TOOK CARE OF THEM, IF THEY WERE
ENROLLED AS WELL, WOULD ALSO GET
A SURVEY AND THEY WOULD COMPLETE
AN EMAIL SURVEY BECAUSE THE
PROVIDERS WANTED EMAILS.
THE INDIVIDUALS WITH SICKLE CELL
WANTED TEXT.
SO THEY BOTH WERE ASKED TO
COMPLETE A FOLLOW-UP SURVEY
AFTER AN ED VISIT.
SO WHERE ARE WE TODAY, WHICH IS
PRETTY MUCH WHAT I'M REALLY
REPORTING ON TODAY.
THE TARGET WAS, WE WERE HOPING
EACH SITE WOULD ENROLL ABOUT 40
PATIENTS AND GET 20 UNIQUE
PATIENTS COMPLETING THE
FOLLOW-UP ED SURVEY.
SO OUR TARGET WAS 160 UNIQUE
PATIENTS WITH FOLLOW-UP SURVEYS,
AND I COULDN'T BE HAPPIER TO SAY
THAT I THINK LAST WEEK WE HIT
IT, AND SO WE DO HAVE 160 UNIQUE
PATIENT FOLLOW-UP SURVEYS WHICH
IS PHENOMENAL, GIVEN ALL OF THE
COVID CRAZINESS.
BECAUSE IT DID DEFINITELY KEEP
SOME PATIENT AWAIL FROM THE
EMERGENCY DEPARTMENT FOR QUITE A
PERIOD OF TIME.
SO COMPLETING THE STUDY WAS A
CHALLENGE, AND REALLY ALL OF THE
SITES AND ALL OF THE
COORDINATORS AT EACH SITE, ALL
THE INVESTIGATORS AT EACH SITE
WERE SO COMMITTED AND SO
DEDICATED TO COMPLETING THIS,
EVEN AFTER THIS INITIAL GRANT
FUNDING ENDED, THAT IT REALLY IS
ONLY BECAUSE OF THE DEDICATION
OF REALLY EVERYONE, EVERYBODY
INVOLVED AT EACH SITE THAT WE
HIT THIS NUMBER.
I'M STILL AMAZED THAT WE HIT THE
NUMBER.
I COULDN'T BE HAPPIER.
SO WE DID ENROLL 280 PATIENTS
THAT SIGNED CONSENT.
THE PRIMARY OUTCOME IS BASED ON
ONLY ONE VISIT FROM THAT
PATIENT, SO THE FIRST ED VISIT
THEY WOULD HAVE.
HOWEVER, IF THEY HAD MORE THAN
ONE VISIT, THEY WERE SENT
SURVEYS.
I THINK UP TO ABOUT FIVE IN A
PARTICULAR MONTH.
WHERE THEY COULD ACTUALLY
COMPLETE THE SURVEY MORE THAN
THAT.
SO WE DO HAVE 329 POST-ED
SURVEYS BUT 160 WITH UNIQUE
PATIENTS.
WE TRAINED 881 ED PROVIDERS, 40R
SURVEYS, AND 243 COMPLETED POST
ED SURVEYS.
WHAT WAS REALLY EXCITING WAS
149 -- WE HAD ALMOST 150, OF 149
PAIRED SURVEY, SO WE HAVE A
RESPONSE FROM THE PATIENT AND
RESPONSE FROM THE PROVIDER ON
THE SAME PARTICULAR VISIT.
I DO THINK SOME OF THIS RESPONSE
RATE FROM THE PATIENTS IN
COMPLETING ALL THE SURVEYS
AFTERWARDS AND FROM THE
PROVIDERS WAS REALLY, AGAIN,
JUST DUE TO THE ENTHUSIASM FOR
THIS PROJECT FOR THE IMPORTANCE
OF THIS PROJECT TO BOTH PATIENT
AND TO THE ED PROVIDERS AS WELL.
THEY DID NOT HAVE TO ANSWER
THESE SURVEY, AND THEY REALLY
DID.
SO I THINK THAT IS REALLY ALL OF
WHAT WE HAVE RIGHT TODAY.
WHERE WE ARE RIGHT NOW IS WE
ACTUALLY HAVE ANALYZED THE
BASELINE SURVEY FOR BOTH THE
PATIENTS AND THE PROVIDERS, AND
WE DO HAVE THAT DATA.
WE HAVE STARTED TO LOOK AT THAT
DATA.
IT'S INTERESTING DATA, AND SO
WE'RE NOT COMFORTABLE TODAY
SHARING IT, BUT WE ARE GETTING
READY, WE DID SUBMIT AN ABSTRACT
TO ASH WITH IT AND WE'LL NEED TO
REALLY TALK ABOUT IT WITH THE
CONSORTIUM INVESTIGATORS FIRST,
I THINK, BEFORE WE GO FORWARD,
AND THEN WE'RE PLANNING MANY
PAPERS, THERE'S LOTS OF
IMPLEMENTATION AROUND THIS
PROJECT, AND THEN WE'LL HAVE
HEALTHCARE UTILIZATION OU OUTCO,
AND THE PRIMARY OUTCOMES AS
WELL.
SO WE'RE REALLY VERY EXCITED
ABOUT COMPLETING THIS, AND
GETTING IT WRAPPED UP TO GET THE
DATABASE LOCKED UP AS WELL,
BECAUSE THE SITES DO STILL NEED
TO HAVE SOME TIME TO FINISH TO
ENTER SOME OF THEIR HEALTHCARE
UTILIZATION DATA, WHICH IS
MEASURED 12 MONTHS PRIOR TO
ENROLLMENT AND 12 MONTHS AFTER
ENROLLMENT, IF WE HAVE 12 MONTHS
AFTER THE PATIENT-SIGNED
CONSENT.
THAT'S IT.
SO THANK YOU, EVERYBODY, FOR
THIS OPPORTUNITY TO PRESENT
TODAY.
>> THANK YOU, DR. TANABE.
OUR NEXT SPEAKER IS DR. PRIYA
PARIKH.
>> THANK YOU, DR. GIBSON.
GOOD MORNING.
I'M A 30-YEAR PEDIATRIC
HEMATOLOGY ONCOLOGY FELLOW HERE
AT UCSF CHILDREN'S HOSPITAL.
TODAY I'M REALLY THRILLED TO
HAVE THE OPPORTUNITY TO SPEAK ON
THIS PROJECT ON BEHALF OF MYSELF
AND MY COCOLLABORATORS.
HERE IS OUR STUDY ENTITLED THE
EVALUATION OF THE IMPACT OF
COVID-19 ON INDIVIDUALS WITH
SICKLE CELL DISEASE IN THE U.S.
USING PATIENT-REPORTED OUTCOMES.
AS WE KNOW, COVID-19 PANDEMIC
HAS CREATED A LOT OF
LONG-STANDING EFFECTS ON
PERSONAL HEALTH, SOCIAL HEALTH
AND MORE GENERALLY THE WORLD IN
WHICH WE LIVE IN.
WE NE HEALTH INEQUITIES HAVE
ALSO BEEN BROUGHT TO LIGHT IN
PHYSICAL HEALTH MEASURES AS WELL
AS MENTAL HEALTH, RESILIENCY AND
DISCRIMINATION ALL IN THE
SETTING OF INCREASED SYSTEMIC
RACISM.
THOSE WHO HAVE HAD LONG-STANDING
EFFECTS WITH RACISM AND HEALTH
INEQUITIES WITHIN OUR HEALTHCARE
SYSTEM REALLY ARE OUR PATIENTS
AND FAMILIES WITH SICKLE CELL
DISEASE.
WONDERFUL WORK HAS BEEN DONE SO
FAR TO UNDERSTAND THE CLINICAL
IMPACT OF COVID-19 FOR OUR
PATIENTS, INCLUDING A LEDGE
INDUSTRY THROUGH DR. PINTO'S
WORK ENTITLED SECURE-SCD.
WHAT HASN'T BEEN YET WELL
DESCRIBED, THOUGH, IS HOW OUR
PATIENTS HAVE DESCRIBED THEIR
EXPERIENCES IN THEIR OWN WORDS
DURING THE COVID-19 PANDEMIC.
SO OUR STUDY SPECIFICALLY AIMS
TO ADD IN A PATIENT VOICE DURING
PATIENT-REPORTED OUTCOMES
INCLUDING MEASURES OF EMOTIONAL
DISTRESS, PAIN AND PSYCHOSOCIAL
WELL-BEING.
IN ADDITION TO UNDERSTANDING
CLINICAL PRESENTATION OF
COVID-19 FOR A COVID-POSITIVE
PATIENT COHORT, OUR FOCUS AS I
MENTIONED IS REALLY
UNDERSTANDING THE
PATIENT-REPORTED PAIN
EXPERIENCE, THE PSYCHOSOCIAL
WELL-BEING AND GENERAL HEALTH
AFFECTED THROUGHOUT THE COVID-19
PANDEMIC.
I THINK THIS WILL REALLY PROVIDE
A GAP IN THE LITERATURE THAT
CURRENTLY EXISTS AND SORT OF
REPRESENTING THE PATIENT VOICE
THROUGHOUT THIS REALLY
UNPRECEDENTED TIME WE'RE ALL
FACING IN OUR TIME.
WE HYPOTHESIZE ADOLESCENTS AND
ADULTS WITH SICKLE CELL DISEASE
WILL EXPERIENCE A MORE NEGATIVE
PSYCHOSOCIAL IMPACT DURING THE
PANDEMIC IN THESE VERY SPECIFIC
MEASURES OF EMOTIONAL DISTRESS,
SOCIAL FUNCTIONING, AND OVERALL
HEALTH.
IN TERMS OF METHODS FOR OUR
STUDY, I KNOW THERE'S A LOT OF
WORDS ON THE SLIDE BUT I WANT TO
HIGHLIGHT A COUPLE POINT.
YOU'VE HAD THE OPPORTUNITY TO
HEAR A LITTLE BIT ABOUT THE
SCDIC AND OVERALL CONSORTIUM
WORK THROUGH DR. GIBSON'S
WONDERFUL OVERVIEW AND THE OTHER
PROJECTS THAT HAVE BEEN ONGOING.
OUR FOCUS IN THIS STUDY IS TO
USE EXISTING PATIENT FOLLOW-UP
SURVEY DATA IN ADDITION TO THE
CREATION OF A COVID-19-SPECIFIC
PATIENT SURVEY THROUGHOUT THE
CONSORTIUM THAT WAS IMPLEMENTED
IN 2020.
THE TIMELINE OF THAT SURVEY
DISTRIBUTION AND ANALYSIS WAS
SPECIFICALLY SEPTEMBER 2020 TO
JUNE 2021, SO SHORTLY AFTER THE
EMERGENCE OF THE PANDEMIC.
THE POPULATION INCLUDING OUR
INCLUSION CRITERIA IS ADOLESCENT
AND YOUNG ADULT POPULATIONS
ENROLLED IN THE SCDIC REGISTRY
WHO ARE PRIMARILY WITHIN THE
AGES OF 15 AND 45, AND MORE
SPECIFICALLY THOSE WHO COMPLETED
BOTH THE COVID-19 SURVEY AS WELL
AS AN ANNUAL FOLLOW-UP SURVEY,
WITHIN A MONTH OR SO OF EACH
OTHER.
IN TERMS OF OUR DESIGN FOR THE
STUDY, WE ARE DOING THIS
RETROSPECTIVELY, IT RETROSPECTIE
AND DESCRIPTIVE AND SURVEY-BASED
INCLUDING PATIENT-REPORTED
CLINICAL OUTCOMES AND MEASURES.
I WANTED TO POINT ATTENTION TO
THE SURVEYS WE UTILIZED WHICH
INCLUDE THE NOVEL CORONAVIRUS
AND COVID-19 PATIENT IMPACT
SURVEY WILL WISCONSIN I'LL SPEAK
A LITTLE BIT MORE ABOUT, THE
PATIENT FOLLOW-UP SURVEY AND WE
ALSO INCLUDED AN INSTITUTIONAL
CLIMATE SURVEY FOR EACH SITE
THAT PARTICIPATED IN THE STUDY
JUST TO GET A MORE GENERAL SENSE
OF TIME LIME OF COVID-19 IMPACT
INCLUDING VACCINATION, ET
CETERA.
TO TOUCH A LITTLE BIT MORE
SPECIFICALLY ON THE PATIENT
IMPACT SURVEY, IT WAS DEVELOPED
IN 2020 AND INCLUDES A SET OF 20
QUESTIONS.
OVERALL VARIABLES IN THIS SURVEY
INCLUDED OUTCOMES SURROUNDING
CLINICAL MEASURES, HEALTHCARE
ACCESS AND UTILIZATION, AS WELL
AS PSYCHOSOCIAL IMPACT THROUGH A
COMBINATION OF CHECK BOX
QUESTIONS AND SCALES.
THOSE PSYCHOSOCIAL IMPACT
QUESTIONS WERE REALLY IN BIG
BUCKETS OF SOCIAL BEHAVIORS,
RELATIONSHIPS, MOOD, STRESS,
SLEEP, FINANCIAL BURDEN.
FROM OUR SCDIC FOLLOW-UP SURVEY,
WE ALSO IDENTIFIED AS A GROUP
THE FOLLOWING VARIABLES AND
PLANS USING OUTCOMES AND -- THEY
WERE DRAWN FROM THE HEALTH
MEASURES COLLECTION THAT ARE
REALLY CONSISTING OF MEASUREMENT
SYSTEMS LOOKING AT PHYSICAL,
MENTAL, SOCIAL HEALTH, SYMPTOMS,
LIFE SATISFACTION.
THESE INCLUDED THE MAJOR BUCKETS
OF PROMISE, PATIENT-REPORTED
OUTCOMES MEASUREMENT INFORMATION
SYSTEM, THE ADULT SICKLE CELL
QUALITY OF LIFE MEASUREMENT
INFORMATION SYSTEM OR ASCQ-ME AS
WELL AS THE TOOLBOX.
THESE ARE SORT OF VALIDATED
TOOLS THAT HAVE FOUND TO BE
SOUND IN ALL OF THESE DIFFERENT
GENERAL BUCKETS OF PHYSICAL
HEALTH, PSYCHOSOCIAL AND
EMOTIONAL MENTAL HEALTH AS WELL.
SO DETAILED HERE ARE SORT OF THE
OVERALL VARIABLES THAT WE HAD
INCLUDED AND PLAN TO INCLUDE IN
OUR OVERALL ANALYSIS, INCLUDING
ASCQ-ME, PROMISE, AS WELL AS
EXPERIENCES OF DISCRIMINATION,
WITH OVERALL LOOKING AT OUTCOMES
OF PROMIS EMOTIONAL DISTRESS,
DEPRESSION, ANXIETY, AS WELL AS
PROMIS GLOBAL HEALTH.
I'M HAPPY TO SHARE A COUPLE
INITIAL RESULTS HERE THAT ARE
MORE DESCRIPTIVE IN NATURE.
IN TOTAL, FOR OUR PROJECT, WE
HAD AN ANALYSIS GROUP OF
653 PATIENTS, AND JUST AS A
REMINDER, THOSE ARE THOSE WHO
FINISHED BOTH COVID-19 AS WELL
AS WHAT WAS THE FOLLOW-UP
SURVEY.
THIS INCLUDES BREAKDOWN BY SCDIC
SITES WHICH WE SEE A NICE
REPRESENTATION OF ALL OF OUR
EIGHT SITES, AS WELL AS
DEMOGRAPHICS BY AGE, SEX AND
ETHNICITY.
IN TERMS OF ACCESS TO CARE, WE
FOUND THAT THE MAJORITY OF OUR
PATIENTS STILL HAD IN-PERSON
VISIT DURING THIS TIME PERIOD.
BUT AS I THINK WE ALL KNOW,
VIDEO AND PHONE VISITS WERE ALSO
HAPPENING AND SORT OF EMERGING
AND BECOMING MORE COMMON
THROUGHOUT THE PANDEMIC.
INTERESTINGLY, SOCIAL BEHAVIORS
WERE VARIED, AS WELL AS SORT OF
RELATIONSHIPS AND HOW THAT
CHANGED THROUGHOUT THE PAN
DEPUBLIC.
MOST IMPACTED IN TERMS OF SOCIAL
MEASURES WERE THINGS LIKE GOING
OUT TO EAT AT RESTAURANTS, MOOD,
SLEEP, STRESS AND SPECIFICALLY
FINANCIAL STRESS.
WE SAW IN GENERAL EITHER STABLE
SOCIAL -- AS A RESULT OF THESE
IMPACTS.
HERE IS JUST A BRIEF OVERVIEW OF
OUR COVID POSITIVE PATIENT
COHORTS.
PATIENTS WHO HAD SELF-IDENTIFIED
AS HAVING COVID INFORECAST AND
WAINFECTION,WANTED TO UNDERSTANF
CLINICAL EXPERIENCES THEY ALL
HAD, SO I WOULD SAY IN GENERAL,
MOST OF OUR YOUNG ADULT
ADOLESCENT PATIENTS REALLY
EXPERIENCED SYMPTOMS OF FEVERS,
CHILLS, COUGH, SHORTNESS OF
BREATH, PAIN, FATIGUE, MYALGIA,
HEADACHE AND LOST OF TASTE AND
SMELL AND THOSE WERE SORT OF THE
MOST OVERALL COMMONLY REPORTED
SYMPTOMS.
I WANTED TO JUST GIVE A GENERAL
SENSE OF WHERE WE INTEND TO GO
FOLLOWING SOME OF THIS INITIAL
DESCRIPTIVE WORK THAT'S BEEN
DONE.
WE REALLY PLAN TO USE UNIVARIATE
AND MULTIVARIATE ANALYSES USING
THESE VALIDATED PRO FRAME WORKS
AS PREVIOUSLY DISCUSSED AND IN
PREVIOUS SLIDES, AS WELL AS THE
ADDITION OF THE COVID-19
VARIABLE AND UNDERSTANDING HOW
BOTH PATIENTS OVERALL THROUGHOUT
THE PANDEMIC HAVE SORT OF
EXPERIENCED THEIR SICKLE CELL
DISEASE AND HOW THAT MAY HAVE
CHANGED IF THEY TRULY HAD
COVID-POSITIVE DISEASE.
WE PLAN TO UNDERSTAND IN OUR
RESULTS WITHIN THE CONTEXT OF
WHAT I THINK IS REALLY IMPORTANT
TO HIGHLIGHT HERE, WHICH IS A --
THAT GO HAND IN HAND WITH A
PANDEMIC AND I THINK WE DON'T
HAVE SO MUCH TIME TO TALK ABOUT
THAT TODAY, BUT I THINK WE'RE
ALL VER VERY AWARE THAT SYSTEMIC
RACISM AND DISCRIMINATION SAW AN
UPTICK DURING THE PANDEMIC AND
ESPECIALLY FOR OUR PATIENTS.
SO THAT HAS BEEN WELL DESCRIBED
AND A WELL-KNOWN I PHENOMENON TT
HAS BEEN HAPPENING THROUGHOUT
THIS PANDEMIC.
I WILL POINT OUT A COUPLE
LIMITATION HERE.
I THINK SAMPLE SIZE IS ALWAYS
SOMETHING TO THINK ABOUT, THE
NATURE OF PATIENT-REPORTED
OUTCOMES, OUR GOAL AND INTENTION
IS REALLY TO ADD IN THE PATIENT
VOICE, BUT WE DID NOT VERIFY
SOME OF THIS DATA THROUGH
MEDICAL RECORDS, INSURANCE
CLAIMS, ET CETERA.
RECONCILING DISKREP K DISCREPANS
SOMETHING WE'VE BEEN WORKING ON
BETWEEN OUR COVID-19 IMPACT
SURVEY AND THE FOLLOW-UP PLAN IN
PLACE WITH SCDIC.
AND THE OTHER THING IS THE
VARYING CHANGES TO THE COVID-19
CLIMATE EVEN WITHIN THE STUDY
PERIOD.
AS MOST OF US ARE VERY FAMILIAR,
THE PANDEMIC HAS NOT BEEN A
LINEAR PROCESS, AND
VACCINATIONS, DIFFERENT
EXPERIENCE AS WELL AS
GEOPOLITICAL CLIMATES HAVE
VARIED A LOT.
AND JUST TO WRAP UP, NEXT SLIDE,
BRIEFLY WANTED TO ACKNOWLEDGE
HERE MY COCOLLABORATORS, MY
PRIMARY MENTOR, DR. MARCIA
TREADWELL AND ALL OUR PATIENTS
AND THOSE AFFECTED BY THE
COVID-19 PANDEMIC.
I WILL WRAP UP THERE AND HAND IT
BACK OFF TO DR. GIBSON.
THANK YOU SO MUCH.
>> THANK YOU VERY MUCH,
DR. PARIKH.
I THINK YOU HAVE A COUPLE
QUESTIONS IN THE Q & A, IF YOU
CAN CHECK AND FOLLOW UP WITH
THEM.
THANK YOU.
OUR NEXT SPEAKER IS
DR. STEPHANIE IBEMERE.
>> GOOD AFTERNOON.
I'M GOING TO SHARE MY SCREEN.
HELLO AND GOOD DAY TO YOU ALL.
I HOPE YOU CAN HEAR ME CLEARLY.
MY NAME IS DR. STEPHANIE
IBEMERE.
I OOM ASSISTANT PROFESSOR IN THE
DUKE UNIVERSITY SCHOOL OF
NURSING.
I'D LINING TO I'D LIKE TO STARTY
THANKING THE NHLBI FOR THE
OPPORTUNITY TO PRESENT HERE
TODAY.
I'D LIKE TO ALSO SAY A SPECIAL
THANK YOU TO THIS MAGNIFICENT
CO-AUTHOR TEAM THAT YOU'RE
SEEING HERE FOR THEIR ENTHUSIASM
FOR THIS STUDY, AND OF COURSE
FOR THEIR SUPPORT AS WE WORK TO
GET THIS MANUSCRIPT PUBLISHED.
SO ON BEHALF OF THIS WONDERFUL
TEAM, I'M HAPPY TO PRESENT OUR
STUDY TO YOU ALL TODAY ENTITLED
HIGH BODY MASS INDEX IN ADULTS
WITH SICKLE CELL DISEASE, A
REPORT FROM THE SICKLE CELL
DISEASE IMPLEMENTATION
CONSORTIUM REGISTRY.
SO THESE ARE DISCLOSURES IN AND
FUNDING STATEMENTS.
AGAIN THANK YOU TO THE NHLBI FOR
YOUR SUPPORT OF THE CONSORTIUM.
SO BODY MASS INDEX IS INCREASING
EACH YEAR IN THE UNITED STATES
AND ACROSS ALL POPULATIONS AND
AS WE KNOW, COVID-19, I DON'T
KNOW ABOUT YOU GUYS, WAS NOT
KIND TO ME AND HAS NOT BEEN KIND
TO THE GENERAL POPULATION IN
TERMS OF WEIGHT GAIN.
THIS BODY MASS INCREASE IS
PARTICULARLY EVIDENT IN THE
AFRICAN AMERICAN POPULATION
WHERE APPROXIMATELY 76.1% OF
THOSE IN THIS POPULATION ARE
CLASSIFIED AS BEING OVERWEIGHT
OR OBESE COMPARED TO 69.8% IN
THE WHITE POPULATION.
SICKLE CELL DISEASE IS A
CONDITION WE KNOW PRO DOMINANTLY
APREDOMINANTLYAFFECTS THOSE WITT
STATUS GIVEN DEMANDS ASSOCIATED
WITH THE DISEASE PROCESS.
HOWEVER, EXTANT LITERATURE IS
SHOWING THAT BMI, BODY MASS
INDEX, ARE INCREASING IN THE
PEDIATRIC SICKLE CELL DISEASE
POPULATION.
HOWEVER, DATA ABOUT THE ADULT
SICKLE CELL DISEASE POPULATION
HAVE BEEN CONFLICTING OVERALL
AND THIS IS DUE TO VARYING
METHODS OF CATEGORIZING BODY
MASS INDEX, THE USE OF SMALL
SAMPLE SIZES IN THESE STUDIES
AND THE USE OF DATA FROM SINGLE
INSTITUTIONS THAT RESULTS IN
INCONCLUSIVE RESULTS.
SO GIVEN THE INCREASING BODY
MASS INDEX IN THE POPULATION AND
OUR LIMITED AVAILABLE EVIDENCE
ON BMI STATUS FOR THOSE THAT ARE
ADULTS WITH SICKLE CELL DISEASE,
THE PRIMARY OBJECTIVE OF THIS
PARTICULAR STUDY WAS TO
DETERMINE THE PREVALENCE OF
OVERWEIGHT AND OBESE BMI STATUS
AMONG ADULTS WITH SICKLE CELL
DISEASE AGED 20 TO 45
PARTICIPATING IN THE SICKLE CELL
DISEASE IMPLEMENTATION
CONSORTIUM REGISTRY.
OUR SECOND DI OBJECTIVE WAS TO
IDENTIFY ASSOCIATIONS BETWEEN
SOCIODEMOGRAPHIC SICKLE CELL
DISEASE AND NON-SICKLE CELL
DISEASE RELATED CLINICAL
CHARACTERISTICS.
HYDROXYUREA USE, AND HIGH BODY
MASS INDEX IN ADULTS WITH SICKLE
CELL DISEASE.
SO THIS STUDY AS I MENTIONED WAS
CONDUCTED UTILIZING DATA FROM
THE SCDIC REGISTRY.
THE CONSORTIUM CONSISTS OF EIGHT
COMPREHENSIVE SICKLE CELL
CENTERS, AS DR. GIBSON HAD
SHARED BEFORE, AND ONE DATA
COORDINATING CENTER.
AND AS WAS NOTED, THE PURPOSE OF
THE SCDIC WAS TO DESIGN AND
ASSESS STRATEGIES TO IMPROVE
SICKLE CELL DISEASE OUTCOMES
THROUGH -- AND THE ESTABLISHMENT
OF A SICKLE CELL DISEASE
REGISTRY CONTAINING CLINICAL AND
PATIENT-REPORTED OUTCOMES.
SO FOR THIS PARTICULAR STUDY, WE
CONDUCTED A CROSS-SECTIONAL
EPIDEMIOLOGICAL ANALYSIS
UTILIZING DATA FROM PARTICIPANTS
WHO WERE CONSENTED TO
PARTICIPATE IN THE REGISTRY DATA
COLLECTION PORTION OF THIS
STUDY, AND WHO WERE BETWEEN THE
AGES OF 20 AND 45 YEARS.
WE EXCLUDED PARTICIPANTS IF THEY
HAPPENED TO BE PREGNANT UPON
REGISTRATION -- EXCUSE ME --
REGISTRY ENROLLMENT OR IF THEY
HAD ANY MISSING DATA.
WE HA ANALYZED DATA GATHERED FRM
MEDICAL RECORD ABSTRACTION, WE
ALSO USED MEDICAL ABSTRACTIONS
ON THE MEDICAL HISTORY OF
NON-SICKLE CELL DISEASE
COMPLICATIONS, WHICH ARE THINGS
LIKE DIABETES OR HYPERTENSION.
WE ALSO ASSESSED
SOCIODEMOGRAPHIC CHARACTERISTICS
SUCH AS AGE, SEX, INSURANCE
STATUS, AND PATIENT-REPORTED
OUTCOMES SUCH AS WHAT PRIYA JUST
PRESENTED FROM THE PROMIS
SCALES.
THESE PARTICULARLY INCLUDED
SICKLE CELL PAIN FREQUENCY AND
SEVERITY.
WE ALSO LOOKED AT EMOTIONAL
DISTRESS.
HOWEVER, THAT DID NOT COME OUT
AS YOU WILL SEE IN THE RESULTS
AS AN IMPORTANT VARIABLE HERE.
WE CONDUCTED BU BI VARIATE
ANALYSIS, FINALLY WE CONDUCTED A
MULTIVARIABLE LOGISTIC
REGRESSION WITH BACKWARD
ELIMINATION TO IDENTIFY WHICH
FACTORS WERE INDEPENDENTLY
ASSOCIATED WITH OVERWEIGHT OR
OBESE STATUS.
SO OUR TOTAL SAMPLE INCLUDED
1,664 PARTICIPANTS.
THE MEAN AGE OF THIS GROUP WAS
30.2 YEARS, AND MEDIAN BMI FOR
THIS POPULATION OF PATIENTS IN
THIS COHORT WAS 23.9 KILOGRAMS
PER METER SQUARED, WHICH
ACTUALLY FALLS INTO THAT NORMAL
BODY MASS CATEGORY.
MOST OF THE POPULATION ALSO
REPORTED A HOUSEHOLD INCOME NEAR
THE POVERTY LINE.
SO IN THIS COHORT SPECIFICALLY,
42.9% OF THE STUDY SAMPLE FELL
INTO THIS OVERWEIGHT AND OBESE
CATEGORY WHERE OBESE STATUS WAS
MOST PREVALENT AMONG THE SITES
IN THE SOUTH.
, WHERE MOST PEOPLE
WERE OBESE IN THE SOUTHWEST AND
SOUTHEAST.
SO ON THIS SLIDE, WE HAVE THE
RESULTS OF OUR MULTIVARIABLE
LOGISTIC REGRESSION.
REGISTRY PARTICIPANTS WHO WERE
FEMALE OR WERE OLDER, AND
REPORTED HAVING HYPERTENSION HAD
HIGHER ODDS OF BEING OVERWEIGHT
OR OBESE.
IN OUR UNIVARIATE ANALYSIS, THE
HYDROXYUREA EFFECT APPEARED TO
VARY BY GENOTYPE, THUS WE
INCLUDED HYDROXYUREA IN OUR
LOGISTIC REGRESSION AS AN
INTERACTION TERM.
WE EXAMINE MODELS IN WHICH
HYDROXYUREA AND GENOTYPE WERE
ENTERED INTO THE MODEL AS
SEPARATE VARIABLES.
HOWEVER, WE RETURNED SIMILAR
RESULTS AS WHAT IS PRESENTED IN
THIS MODEL HERE.
AS CAN BE SEEN HERE, WHEN
COMPARED TO THE GENOTYPE SS, S
BETA ZERO AND WITH NO
HYDROXYUREA USE, THOSE WHO HAD
THE GENOTYPE OF SC/S BETA PLUS,
REGARDLESS OF THEIR HYDROXYUREA
USE, AND THOSE WITH THE GENOTYPE
SS/S BETA ZERO REPORTING
HYDROXYUREA USE WERE MORE LIKELY
TO BE OVERWEIGHT OR OBESE IN
THIS PARTICULAR COHORT.
SO IN THIS STUDY, WE DI DESCRIBD
THE PREVALENCE OF HIGH BMI IN
ADULTS WITH SICKLE CELL DISEASE
WHICH IS HIGHER THAN EXPECTED AS
CURRENT LITERATURE SUGGESTS
OVERWEIGHT AND OBESE STATUS
RANGES FROM 20 TO 28%.
IN OUR STUDY, WE FOUND 42.9%.
WE IDENTIFIED ASSOCIATIONS
BETWEEN HIGH BMI, AGE, SEX,
HYPERTENSION AND THE INTERACTION
TERM OF -- AND HYDROXYUREA USE.
THESE IMPLICATIONS FOR SICKLE
CELL DISEASE MANAGEMENT AS BOTH
PATIENTS AND PROVIDERS CAN
BENEFIT FROM ADDITIONAL
EDUCATION AND RESOURCES ABOUT
BMI, NUTRITION RELATED TO SICKLE
CELL DISEASE AND THEIR RELATION
TO SICKLE CELL DISEASE
MORBIDITY.
SO MORE DATA ARE NEEDED TO
FURTHER CHARACTERIZE THIS
RELATIONSHIP BETWEEN HIGH BMI
STATUS, SICKLE CELL DISEASE AND
NON-SICKLE CELL DISEASE
CO-MORBID ITSCOMORBIDITIES WITHF
DEVELOPING STRATEGIES WHICH CAN
AMCAN -- BETTER UNDERSTANDING OF
BMI STATUS.
IESM GOING TO END THERE, AND
THANK YOU VERY MUCH FOR THIS
PRESENTATION TODAY.
>> THANK YOU VERY MUCH,
DR. IBERMERE.
YOU MAY HAVE SOME QUESTIONS IN
THE Q & A AND IN THE CHAT.
EXAWN OUR LAST SPEAKER FOR THIS
SESSION IS DR. ELEANOR
STEVENSON.
>> GOOD MORNING.
THANK YOU FOR ALLOWING ME TO
PRESENT OUR STUDY.
I'M ELEANOR STEVENSON.
I AM A CLINICAL PROFESSOR AT THE
DUKE UNIVERSITY SCHOOL OF
NURSING AND ALONG WITH MY
COLLEAGUES, WE ARE PRESENTING A
STUDY TITLED INFER TELL OUTCOMES
AMONG FEMALES AND MALES WITH
SICKLE CELL DISEASE IN THE SCDIC
REGISTRY.
SO THESE ARE OUR DISCLOSURES.
SO A LITTLE BIT OF BACKGROUND.
BOTH WOMEN AND MEN CAN
EXPERIENCE INFERTILITY.
INFERTILITY IS DEFINED THROUGH
THE WORLD HEALTH ORGANIZATION AS
THE INABILITY TO CONCEIVE A
PREGNANCY AFTER 12 MONTHS OF
REGULAR UNPROTECTED INTERCOURSE.
AMONGST THE POPULATION OF PEOPLE
WITH SICKLE CELL, FEMALES ARE AT
INCREASED RISK FOR DIMINISHED
OVARIAN RESERVE.
AND MALES WITH SICKLE CELL
PRESENT WITH DELAYED PUBERTY,
LOW TESTOSTERONE AND SPERM
ABNORMALITIES DUE TO TESTICULAR
DYSFUNCTION.
SO INFER T INFERTILITY NATIONALY
AFFECTS ABOUT 12 TO 15% OF THE
U.S. POPULATION, BUT IT'S
CURRENTLY UNKNOWN IF THERE
ARE -- WHAT THE INCIDENCE IS
AMONGST THOSE WITH SICKLE CELL.
THERE ARE NO KNOWN PUBLISHED
REPORTS THAT PRESENT INFERTILITY
INCIDENCE OR TREATMENT SEEKING
FOR BOTH MEN OR WOMEN WITH
SICKLE CELL DISEASE.
SO WE NEED MORE INFORMATION TO
UNDERSTAND INFERTILITY FOR THOSE
INDIVIDUALS WITH SICKLE CELL SO
WE CAN IMPROVE CLINICAL CARE.
SO THE AIMS WERE TO DESCRIBE THE
PREVALENCE OF FEMALE AND MALE
FACTOR INFERTILITY IN PERSONS
WITH SICKLE CELL DISEASE IN THE
REREGISTRY, TO DESCRIBE
INFERTILITY TREATMENT SEEKING
AMONG FEMALES AND MALES WITH
INFERTILITY WHO ARE ENROLLED IN
THE REGISTRY AND DETERMINE IF
THERE ARE DIFFERENCES BETWEEN
FERTILE AND INFERTILE GROUP
BASED ON SOCIODEMOGRAPHIC
STATISTICS.
WE USED CONSORTIUM DATA
COLLECTED USING SELF-REPORT
SURVEYS, MEDICAL RECORDS AND
LABORATORY ABSTRACTION FORMS.
FEMALE AND MALE PARTICIPANTS
COMPLETED DATA COLLECTION FORMS
INCLUDED SEX-SPECIFIC
INFERTILITY QUESTIONS.
OF THE 2,440 PERSONS IN THE
CONSORTIUM, 2374 COMPLETED THOSE
PREGNANCY FORMS AND OF THESE,
THE MAJORITY, 2315 RESPONDED TO
THE THE INF INFERTILITY-RELATED
QUESTIONS.
SO BA BASELINE CHARACTERISTICS
CHARACTERISTICS AND RISK
FACTORS, MEAN AND STANDARD
DEVIATION FOR CONTINUOUS
VARIABLES.
CATEGORICAL VARIABLES WERE USING
FISHER'S EXACT TEST OND
CHI-SQUARE, WE SET A P VALUE OF
LESS THAN .05 AS STATISTICALLY
SPECIFIC.
FIRST UNIVARIATE ANALYSIS WERE
USED AS THE FIRST SCREENING STEP
TO ANALYZE ASSOCIATION BETWEEN
INFERTILITY AND SOCIODEMOGRAPHIC
AND CLINICAL VARIABLES.
NEXT, BIOLOGICALLY AND SOCIALLY
INFLUENTIAL VARIABLES WERE USED
IN A MULTIVARIABLE REGRESSION
MODEL.
BACKWARD ELIMINATION LOGISTIC
REGRESSION WITH AN EXIT
CRITERION OF P LESS THAN .05 WAS
USED TO IDENTIFY STATISTICALLY
SIGNIFICANT COVARIATES AND
DETERMINE A MORE PERSONAL USE
MODEL.
MODEL FITTING INCLUDING A
COMPARISON OF THE FULL AND
REDUCED MODELS TO PROVIDE TESTS
OF AN IMPROVED FIT.
ODDS RATIO AND 95% CONFIDENCE
INTERVALS WERE OBTAINED FOR
VARIABLES IN THE REMAINING FINAL
MODEL.
SO OUR RESULTS, I APOLOGIZE,
THAT N SHOULD BE ACTUALLY 2311.
SO THERE WERE 2311 PARTICIPANTS
IN THE REGISTRY THAT WERE
INCLUDED IN THE FINAL ANALYSIS.
AND JUST TO LOOK AT SOME OF THE
DEMOGRAPHIC BREAKDOWN, THE MEAN
AGE WERE 29.2 YEARS OF AGE.
THE MAJORITY OF THE SAMPLE,
95.6, WERE BLACK, 73% WERE NEVER
MARRIED.
NEARLY 63% WERE INSURED THROUGH
EITHER MEDICARE, MEDICAID,
MILITARY INSURANCE.
73% REPORTED HAVING HEMOGLOBIN
SS GENOTYPE, AND NEARLY 74%
EITHER WERE CURRENTLY OR
PREVIOUSLY TAKING HYDROXYUREA.
SO THE FIRST AIM, PREVALENCE AND
INFER TELL DIAGNOSIS.
INFERTILITY DIAGNOSIS.
OF OUR SAMPLE OF 2311, 23.9%
REPORT THE INFER TELL.
. DEFINED
AS NOT BEING ABLE TO CONCEIVE A
PREGNANCY WITHIN 12 MONTHS OF
UNPROTECTED INTERCOURSE.
THE REASONS FOR INFERTILITY ARE
SHOWN HERE BUT AS YOU CAN SEE,
THE THEY ONLY HAVE DIAGNOSES FOR
A SMALL NUMBER OF THOSE WITH
INFERTILITY AND ON THE NEXT
SLIDE, YOU WILL SEE WHY.
ONLY 22.8%, SO THAT IS AN N OF
100 OF THOSE 441 OF PARTICIPANTS
WHO REPORTED INFERTILITY
ACTUALLY SOUGHT OUT AN
INFERTILITY CONSULTATION.
SO NOT EVEN 25% OF THOSE WHO
WERE EXPERIENCING INFERTILITY
TRIED TO SEEK OUT SOME HELP.
OF THOSE WHO DID, 21.7% WERE
FEMALE AND 25% WERE MALE.
OF THE 100 THAT SOUGHT
CONSULTATION, ONLY 41% RECEIVED
INFERTILITY TESTING.
WHEN YOU CONSIDER 441 REPORTED
INFERTILITY, ONLY 10% ACTUALLY
RECEIVED SOME SORT OF MEDICAL
EVALUATION FOR THEIR
INFERTILITY.
SO AS YOU CAN ALSO SEE, VERY FEW
OF OUR SAMPLE RECEIVED TREATMENT
TO HELP THEM BECOME PREGNANT.
IN A COMPARISON OF THOSE WITH IH
INFERTILITY AND WITHOUT,
SOCIODEMOGRAPHIC CHARACTERISTICS
OF SAMPLE, COMPARED TO
INDIVIDUALS 18 TO 29 YEARS OF
AGE, THOSE WHO WERE 30 TO 34
ACTUALLY HAD MORE THAN TWICE THE
ODDS OF INFERTILITY NOT
SURPRISINGLY AND 35 ABOVE HAD A
1.66% INCREASED ODDS OF
INFERTILITY.
THOSE WITH INFERTILITY WERE LESS
LIKELY TO BE NON-EMPLOYED BY
CHOICE BUT MORE LIKELY TO BE
EMPLOYED.
MARITAL STATUS, DIFFERENT
BETWEEN THE GROUPS.
MALES WHO NEVER HAD BEEN MARRIED
LESS LIKELY TO REPORT
INFERTILITY THAN THEIR MARRIED
COUNTERPARTS.
AND HYDROXYUREA USE AND GENOTYPE
WERE NOT FOUND TO BE DIFFERENT
BETWEEN THE GROUPS.
SO IN SUMMARY, OUR SAMPLE HAD
HIGHER RATES OF INFERTILITY THAP
THE GENERAL PUBLIC.
THAN
THE GENERAL PUBLIC, UP 17% MALES
AND 24% FEMALES.
THIS IS HIGHER THAN THE NATIONAL
TRENDS OF ABOUT 12% MALES AND 11
TO 15% FEMALE, SO MUCH HIGHER
THAN THE NATIONAL AVERAGE.
ONLY A QUARTER OF OUR SAMPLE
WITH INFERTILITY SOUGHT
FERTILITY CONSULTATION, AND THIS
IS ABOUT HALF THE NATIONAL RATE.
SO ABOUT 50% OF PEOPLE IN THE
UNITED STATES WITH INFERTILITY
WILL SEEK CARE FOR THEIR
INFERTILITY.
OF THOSE WHO DID SEEK OUT CARE,
FEWER DID SEEK OUT TREATMENT FOR
IT.
IT'S IMPORTANT TO KNOW THAT
NATIONALLY, WOMEN FROM RACIAL
AND ETHNIC MINORITIES UTILIZE
INFERTILITY SERVICES LESS THAN
NON-HISPANIC WHITE WOMEN.
OF THE 100 PARTICIPANTS IN OUR
STUDY WHO REPORT INFERTILITY,
VERY FEW HAD RECEIVED MEDICAL
HELP IN CONCEIVING.
THE MOST COMMON TREATMENT
OFFERED WAS ADVICE.
ONLY 12 RECEIVED OVULATION
MEDICATIONS SUCH AS CLOAMID FOR
THEIR TREATMENT PLAN.
ONLY ONE REPORTED -- A LARGE
PERCENTAGE OF OUR SAMPLE HAS
GOVERNMENT INSURANCE, WHICH IT'S
IMPORTANT TO NOTE DOES NOT
INCLUDE INFERTILITY TREATMENT.
SO THIS REALLY HAS ACCESSING
POLICY IMPLICATIONS.
INFERTILITY CARE IS REALLY
EXPENSIVE.
JUST AN EVALUATION ALONE CAN BE
UPWARDS OF $500 AND THAT DOESN'T
INCLUDE SOME OF THE ASSOCIATED
TESTING.
TREATMENT IS IN THE THOUSANDS
AND IN VITRO IS UPWARDS OF ABOUT
$20,000 PER CYCLE.
AND SO WITHOUT INSURANCE, THE
COST IS REALLY PROHIBITIVE FOR
MOST PEOPLE.
IN THE U.S. IN GENERAL, THERE'S
LIMITED INSURANCE COVERAGE FOR
INFERTILITY SERVICES.
ONLY 19 STATES HAVE MANDATED
INFERTILITY INSURANCE COVERAGE
LAWS, OF WHICH ONLY 13 STATES
INCLUDE IN VITRO COVERAGE, AND
ONLY 11 STATES MANDATE COVERAGE
FOR FERTILITY PRESERVATION LAWS
FOR IATROGENIC INFERTILITY.
WHILE MEDICAID MAY COVER THE
INFERTILITY EVALUATION, THERE'S
ESSENTIALLY AS I SAID BEFORE NO
COVERAGE FOR TREATMENT.
SO NATIONALLY, THERE IS A HIGHER
SHARE OF BLACK AND HISPANIC
WOMEN THAN WHITE WOMEN WHO ARE
COVERED BY MEDICAID OR
UNINSURED, WHICH IS CONSISTENT
WITH OUR SAMPLE, AND THOSE WITH
SICKLE CELL HAVE HIGHER RATES OF
MEDICAID UNEMPLOYMENT THAN THE
GENERAL BLACK AND HISPANIC
POPULATION, SO INSURANCE
COVERAGE BECOMES A SIGNIFICANT
BARRIER TO ACCESS TO CARE NEEDED
FOR THOSE WITH SICKLE CELL WHO
ARE EXPERIENCING INFERTILITY.
SO AS CARE FOR INDIVIDUALS WITH
SICKLE CELL CONTINUES TO
IMPROVE, SO SHOULD THAT FOR
INFERTILITY.
MORE WORK REALLY IS NEEDED TO
HELP IMPROVE ACCESS TO CARE FOR
INFERTILITY EVALUATION AND
APPROPRIATE TREATMENT FOR THOSE
WHO DESIRE HAVING CHILDREN.
THOSE ARE MY REFERENCES.
WITH THAT, I'M HAPPY TO ANSWER
QUESTIONS.
IF WE HAVE TIME.
>> THANK YOU, DR. STEVENSON.
AND WE HAVE FINISHED ON TIME,
ACTUALLY THREE MINUTES EARLY.
THERE ARE SOME QUESTIONS IN THE
CHAT IN THE Q & A, BUT IF
ANYBODY HAS ANY QUESTIONS FOR
ANY OF THE PANELISTS OR ANYTHING
ABOUT THE SCDIC CONSORTIUM, YOU
HAVE A FEW MINUTES WHERE YOU CAN
TAKE THAT OPPORTUNITY OR WE CAN
TURN EVERYTHING BACK OVER TO
NHLBI.
>> I DON'T SEE ANY HANDS UP AT
THE MOMENT.
AMIR, DO YOU SEE ANY HANDS UP?
OR ALEX, DO YOU SEE ANY HANDS
UP?
I DON'T SEE ANY.
>> ALL RIGHT.
I'LL TURN IT BACK OVER TO YOU.
>> WELL, THANK YOU SO MUCH.
FOR AN EXCELLENT SESSION.
THERE ARE SOME COMMENTS IN THE
CHAT AGAIN, SO PLEASE RESPOND TO
THEM ACCORDINGLY.
SO HERE WE MOVE ON TO OUR NEXT
COMPONENT, WHICH IS THE ARBERY
SEARCH COLLABORATIVE, AND
DR. CHARLES ABRAMS IS GOING TO
BE CHAIRING THIS SESSION, AND
I'LL LET DR. ABRAMS TAKE OVER.
DR. ABRAMS?
>> THANK YOU VERY MUCH.
THANKS, EVERYONE.
I'D LIKE TO THANK JULIE, NAOMI,
ALEX AND EVERYONE WHO HAS BEEN
PUTTING TOGETHER A GREAT
SYMPOSIUM AND FOR THE CHANCE TO
TALK WITH MY COLLEAGUES HERE
TODAY.
SO THIS IS GOING TO BE A
MULTIPART PRESENTATION, IF I
COULD TROUBLE YOU TO ADVANCE TO
THE NEXT SLIDE.
SO I'M JUST GOING TO BE GIVING
AN INTRODUCTION ON THE RESEARCH
COLLABORATIVE OR THE ASH RC AS
WELL AS OUR RESEARCH INITIATIVE,
THEN MY COLLEAGUES ARE GOING TO
BE TALKING ABOUT VARIOUS
COMPONENTS OF IT.
SO ABOUT A HALF A DOZEN YEARS
AGO, THE AMERICAN SOCIETY OF
HEMATOLOGY MADE A COMMITMENT TO
MAKE A DIFFERENCE IN THE CARE OF
INDIVIDUALS WITH SICKLE CELL
DISEASE, AND SO THEY LAUNCHED A
MULTIPRONGED INITIATIVE, AND
THAT INVOLVED WORK ON IMPROVING
ACCESS TO CARE INVOLVED WORK ON
A POLICY LEVEL, A NATIONAL
LEVEL, INVOLVED FORMING A
COALITION OF SICKLE CELL
INTERESTED GROUPS TO GIVE A
VOICE TO THE INDIVIDUALS WITH
SICKLE CELL AND THERE WAS A
GLOBAL INITIATIVE THAT'S STILL
ONGOING WHICH INVOLVES NEWBORN
SCREENING IN SUB-SAHARAN AFER
KA. BUT WAFRICA.THERE WAS ALSO N
IMPROVING RESEARCH AND DOING
THINGS TO DIRECTLY HELP THE CARE
OF INDIVIDUALS WITH THIS
DISEASE, AND SO FOR THAT, THEY
FORMED A RESEARCH COLLABORATIVE
AND IF YOU COULD ADVANCE TO THE
NEXT SLIDE, IT'S WHAT I'D LIKE
TO BE INTRODUCING TODAY.
SO THE ASH RESEARCH
COLLABORATIVE IS DESIGNED TO
FOSTER INTERACTIONS BETWEEN
PEOPLE IN ACADEMIA AND THE
GOVERNMENT AND IN INDUSTRY,
BECAUSE WE BELIEVE THAT
COLLECTIVELY TOGETHER WE CAN
ACCELERATE RESEARCH AND IMPROVE
CARE.
SO THAT IS THE PURPOSE OF THE
ASH RC, AND THE FOCUS MOST
RECENTLY HAS BEEN ON SICKLE CELL
DISEASE.
SO IF YOU WOULD GO TO THE NEXT
SLIDE.
SO THERE ARE TWO MAIN PRONGS TO
THIS RESEARCH ENDEAVOR, AND SO
FIRST THERE'S A CLINICAL TRIAL
NETWORK, AND SO THIS IS COMPOSED
OF SITES AND COMMUNITY MEMBERS,
AND IT PROVIDES THE
INFRASTRUCTURE TO ACCELERATE
SICKLE CELL DISEASE RESEARCH.
AND THEN SECOND, THERE'S A DATA
HUB, AND SO THIS INVOLVES THE
INGESTION OF REAL WORLD DATA, AS
WELL AS THE SICKLE CELL DISEASE
LEARNING COMMUNITY THAT YOU'RE
GOING TO BE HEARING ABOUT THAT
PROMOTES THE IMPLEMENTATION OF
EVIDENCE-BASED PRACTICE TO
IMPROVE SICKLE CELL DISEASE
CARE.
SO IF WE GO TO THE NEXT SLIDE,
THERE ARE GOING TO BE FOUR TALKS
THAT FOLLOW ME.
FIRST, NICOLE MORTIER IS GOING
TO BE GIVING A TALK ON THE
CLINICAL TRIAL NETWORK.
SECOND, KATHLEEN THAHEWITT ON TE
DATA HUB.
EMILY TUCKER ON REAL WORLD
EVIDENCE AND TO WRAP THINGS UP,
ALEXIS THOMPSON IS GOING TO BE
TALKING ABOUT THE LEARNING
COMMUNITY.
SO WITH THAT, IF YOU GO TO THE
NEXT SLIDE, I'D LIKE TO PASS IT
OVER TO NICOLE MORTIER.
>> AS DR. ABRAMS JUST MENTIONED,
THE NETWORK WAS LAUNCHED TO
ENHANCE THE CONDUCT OF CLINICAL
RESEARCH FOR SICKLE CELL
DISEASE.
THE NETWORK, WHICH IS JUST ONE
PART OF THE ARBE ASH RESEARCH
COLLABORATIVE, FACILITATE
OPTIMALLY DESIGNED CLINICAL
RESEARCH TO ADVANCE THE CARE OF
THOSE LIVING WITH SICKLE CELL
DISEASE.
THE NETWORK IS -- SORRY, NEXT
SLIDE.
THE NETWORK IS REALLY BUILT ON
THREE PILLARS.
FIRST, WE HAVE A COMMUNITY
CENTERED APPROACH BRINGING THE
VOICE OF THE SICKLE CELL DISEASE
COMMUNITY TO THE TABLE,
LEVERAGING REAL WORLD DATA,
WHICH YOU'LL HEAR MORE ABOUT
THROUGH THE DATA HUB, AND THEN
SUPPORTING SICKLE CELL DISEASE
RESEARCH BY BRINGING TOGETHER A
COMMUNITY OF RY RESEARCH-READY
CLINICAL SITES AND
INVESTIGATORS, REALLY HELPING TO
FACILITATE EFFICIENT COORDINATED
CLINICAL RESEARCH.
SO LAST YEAR, AT THE NHLBI
AUGUST MEETING, DR. ABRAMS
ANNOUNCED THE FIRST 10 CON SORE
SH THAT HAD BEEN ONBOARDED INTO
THE NETWORK.
SO TODAY, WE HAVE 16 ONBOARDED
CONSORTIA WITH DIRECT
RELATIONSHIP WITH 16 OF THE HUB
SITES, AND THROUGH THOSE 16
ONBOARDED CONSORTIA, THE NETWORK
HAS RELATIONSHIPS WITH ALMOST 80
CLINICAL SITES AND APPROXIMATELY
38,000 CHILDREN AND ADULTS
LIVING WITH SICKLE CELL DISEASE
THAT ARE SPREAD IN EIGHT
GEOGRAPHICALLY DIVERSE AREA THAT
REPRESENTS A GOOD DEAL OF THE
SICKLE CELL DISEASE POPULATION.
SO AS ALSO DISCUSSED IN TALKS
THIS MORNING, ENSURING THAT
WE'RE BUILDING THIS NETWORK WITH
THE SICKLE CELL DISEASE
COMMUNITY IS FOUNDATIONAL TO OUR
MISSION.
AND THE ASH RESEARCH
COLLABORATIVE SICKLE CELL
DISEASE COMMUNITY ADVISORY BOARD
PROGRAM IS REALLY KEY TO THAT
EFFORT.
SO ASH RC IS HELPING TO SUPPORT
THE DEVELOPMENT OF LOCAL
COMMUNITY ADVISORY BOARDS AT
EACH OF THE CONSORTIA BROUGHT
INTO THE NETWORK AND ALSO A
NATIONAL COMMUNITY ADVISORY
BOARD WHICH IS MADE UP OF
REPRESENTATIVES FROM EACH OF
THOSE LOCAL COMMUNITY ADVISORY
BOARDS OR CABs.
BY BRINGING TOGETHER AND
BRINGING THE COMMUNITY VOICE TO
THE TABLE IN DISCUSSION ABOUT
SICKLE CELL DISEASE CLINICAL
RESEARCH AND ENIMAIJING THAT
COMMUNITY EARLY AND OFTEN
THROUGHOUT THE ENTIRE RESEARCH
PROCESS, WE CAN ENSURE THAT
WE'RE ASSESSING THE PRIORITIES
OF THE COMMUNITY WITH REGARDS TO
RESEARCH, GAIN COMMUNITY INPUT
TO IDENTIFY AND ADDRESS BARRIERS
TO RESEARCH PARTICIPATION
ASSOCIATED WITH STUDY DESIGN,
PROMOTE KNOWLEDGE AND COCREATE
EDUCATIONAL RESOURCES WITHIN THE
COMMUNITY TO ADDRESS CONCERNS
AND QUESTIONS ABOUT RESEARCH
THAT CAN THEN BE DISSEMINATED
BEYOND THESE LOCAL COMMUNITY
ADVISORY BOARDS TO THE BROADER
SICKLE CELL DISEASE COMMUNITY,
AND TO REALLY DESIM NATE
INFORMATION ABOUT RESEARCH
OPPORTUNITIES AND OUTCOMES.
MY EXPERIENCE AND I SUSPECT THAT
OF MANY OF US ON THIS CALL IS
THE PERCEPTION OF PERSONS LIVING
WITH SICKLE CELL DISEASE ARE
UNWILLING TO PARTICIPATE IN
RESEARCH IS GREATLY EXAGGERATED.
THE SICKLE CELL DISEASE
COMMUNITY IS VERY MUCH
INTERESTED IN PARTICIPATING IN
THE RESEARCH PROCESS AND
CONTRIBUTING TO THE KNOWLEDGE
THAT WILL IMPROVE THEIR LIVES
AND LIVES OF OTHERS LIVING WITH
SICKLE CELL DISEASE.
WE JUST NEED TO EMPOWER THE
COMMUNITY, ENGAGE THEM WITHIN
THE RESEARCH PROCESS, INCLUDE
THEM IN THE RESEARCH PROCESS AND
NORMALIZE CONVERSATIONS AROUND
RESEARCH.
SO ASH RESEARCH COLLABORATIVE IS
WORKING TO SUPPORT THE SICKLE
CELL DISEASE COMMUNITY AND OUR
RESEARCH SITES TO BUILD A STRONG
CTN INFRASTRUCTURE THAT WILL
ACCELERATE AND SUPPORT SICKLE
CELL DISEASE RESEARCH.
SOME OF THAT SUPPORT INCLUDES
PROVIDING FINANCIAL SUPPORT TO
THE HUB SITE FOR A DEDICATED
STUDY COORDINATOR AND FOR THAT
LOCAL COMMUNITY ADVISORY BOARD
DEVELOPMENT.
TO HELP TO IMPROVE STUDY STARTUP
EFFICIENCY, SITES WITHIN THE
NETWORK HAVE ACCESS TO A CENTRAL
IRB, THE WESTERN CAPERNICUS
GROUP, AND A NETWORK LEVEL
ELECTRONIC TRIAL MASTER FILE IS
CURRENTLY BEING POPULATED TO
STANDARDIZE AND FACILITATE STUDY
LEVEL ESSENTIAL DOCUMENT
COLLECTION.
WE'RE CONNECTING INDUSTRY AND
OTHER INVESTIGATORS TO KEY
OPINION LEADERS WITHIN THE
SICKLE CELL DISEASE CLINICIAN
AND RESEARCH COMMUNITY AS WELL
AS WITH OUR NATIONAL COMMUNITY
ADVISORY BOARDS FOR COMMUNITY
INPUT AND PROTOCOL REVIEWS.
IN ADDITION TO SUPPORTING THE
PIPELINE OF NEW THERAPEUTICS FOR
TREATMENT OF SICKLE CELL
DISEASE, WE REALLY HOPE THAT THE
RESEARCH INFRASTRUCTURE WE'RE
BUILDING AS PART OF THE CLINICAL
TRIALS NETWORK WILL BE USED TO
SUPPORT COLLABORATIVE AND
INVESTIGATOR LED RESEARCH ABOUT
SICKLE CELL DISEASE WE'VE BEEN
HEARING ABOUT OVER THE LAST
COUPLE DAYS AND WE LOOK FORWARD
TO FURTHER DISCUSSIONS.
I'M TURNI'LL TURN IT OVER NOW TY
COLLEAGUE, KATHLEEN HEWITT.
>> HI, EVERYONE.
SPECIAL THANK YOU TO DRS. ABRAMS
AND THOMPSON FOR COORDINATING
THIS SESSION AND TO MY FELLOW
COLLEAGUES AND ALSO TO NHLBI FOR
HAVING US TODAY.
IT'S MY PLEASURE TO SHARE A
LITTLE ABOUT THE DATA HUB
PROGRAM AND THEN I WILL HAND IT
OVER TO EMILY TUCKER WHO'S GOING
TO TALK SPECIFICALLY ABOUT SOME
OF OUR REAL WORLD DATA
INITIATIVES.
SO TO SORT OF LEVEL THE PLAYING
FIELD FOR EVERYONE, IF YOU ARE
AWARE OF THE DATA HUB, I KNOW
BECAUSE I RECOGNIZE YOUR FACES
AND YOUR NAMES, OTHERS MAY NOT
BE SO MUCH.
IF YOU THINK WITH ABOUT THE DA,
ONE OF THE AREAS TO CONSIDER IS
REAL WORLD DATA.
MANY OF US IN THE RESEARCH FIELD
ARE PROBABLY ALREADY INVOLVED OR
BECOMING INVOLVED WITH
UNDERSTANDING THE IMPORTANCE OF
HOW REAL WORLD DATA CAN HELP TO
SUPPORT GENERATION OF REAL WORLD
EVIDENCE.
BUT THERE ARE OTHER USES AS WELL
SO WHY IS THE DATA HUB OF VALUE,
WHY DID ASH INVEST IN BUILDING
AN INFRASTRUCTURE TO SUPPORT IT?
THIS DIAGRAM HERE RUNS
THROUGH -- AND I'LL JUST RUN
THROUGH IT FAIRLY QUICKLY, BUT
SO YOU CAN THINK ABOUT USING
THAT DATA FOR RETROSPECTIVE
RESEARCH USING IT FOR ANALYSIS,
UNDERSTANDING, DOING PRAGMATIC
CLINICAL TRIALS AND
UNDERSTANDING WHAT'S HAPPENING
IN THE REAL WORLD TO HELP
IDENTIFY CLINICAL AREAS THAT
MIGHT NEED SOME ATTENTION AS
WELL AS QUALITY IMPROVEMENT.
ANOTHER IS TO NEST STUDIES.
WHAT WE MEAN BY THAT IS, BY
USING THE DATA THAT WE'RE
CAPTURING FROM THE SITES WHO ARE
PARTICIPATING IN THE DATA HUB
PROGRAM, THAT GIVES US A LARGE
BREADTH OF INFORMATION ABOUT
PEOPLE LIVING WITH SICKLE CELL
DISEASE, BUT TO EXECUTE CERTAIN
PROSPECTIVE CLINICAL STUDY,
ADDITIONAL DATA MAY BE NEEDED.
SO WHEN WE NEST A STUDY WITHIN
THE DATA HUB, WE WOULD USE THE
REAL WORLD DATA BUT ALSO AUGMENT
THAT WITH PROSPECTIVE MORE
MANUAL DATA COLLECTION.
I A 'NOTHER FOCUS AREA IS USING
THE DATA FOR LOCAL AND NATIONAL
QUALITY IMPROVEMENT.
AND WE HAVE A LEARNING COMMUNITY
WHICH WILL BE TALKED ABOUT IN A
LITTLE BIT BY DR. ALEXIS
THOMPSON TO LEARN HOW THESE DATA
ARE BEING USED TO COORDINATE --
THEY COULD ANALYZE AND SEE WHERE
THEY MIGHT HAVE GAPS IN
OPPORTUNITIES TO IMPROVE, THEY
WILL HAVE THEIR OWN LOCAL FOCUS
AREAS.
AND THOSE FOCUS AREAS THEN WILL
INFORM CLINICAL PRACTICE.
AND THINKING ABOUT WAYS IN WHICH
THE WAY CLINICIANS ARE
APPROACHING CLINICAL PRACTICE
LEARNING FROM EACH OTHER, ALSO
LEARNING FROM THOSE WHO ARE
PARTICIPATING IN THE DATA HUB
PROGRAM AND OTHER -- IN OTHER
INSTITUTIONS.
ALSO THE DATA HUB IS
MULTI-STAKEHOLDER, SO WHILE MANY
OF OUR COMMITTEE MEMBERS DO
REPRESENT THOSE THAT HAVE SICKLE
CELL CLINICAL EXPERTISE BUT THEY
ARE IMPLEMENTATION SCIENTISTS,
THEY ARE PSYCHOLOGIST, THEY ALSO
ARE MEMBERS OF THE SICKLE CELL
DISEASE COMMUNITY, THEY
REPRESENT INDUSTRY, THEY WORK
WITH FEDERAL AGENCIES, NHLBI
BEING ONE OF THEM BUT ALSO FDA,
HHS, OFFICE OF MINORITY HEALTH,
AND WE ALSO HAVE SOME MEMBER
FROM CDC WHO PARTICIPATE IN THE
WORK.
AND NETWORK, BRING TOGETHER
REPRESENTATIVES ACROSS ALL OF
THESE DIFFERENT STAKEHOLDER
AVENUES AND TALKING ABOUT AND
BRINGING TO THE HIGHEST LEVEL
WHAT THE NEEDS ARE FOR OUR
PATIENTS WITH SICKLE CELL
DISEASE BUT THROUGH THE DATA
HUB, TRYING TO CAPTURE AS MUCH
DATA AS WE CAN TO HELP INFORM US
HOW CARE IS BEING PROVIDED
ACROSS THE U.S.
SO KEEPING ALL OF THAT IN MIND
AND IF I JUST DRAW YOUR EYES TO
THE RIGHT, REALLY EVERYTHING
DRILLS DOWN TO TWO THINGS.
ONE IS USING THE DATA FOR
RESEARCH AND THE OTHER IS TO
ENHANCE CLINICAL CARE AND DOING
QUALITY IMPROVEMENT.
SO NOW IF I CAN DRAW YOUR EYES
BACK OVER TO THE LEFT, WE START
WITH PEOPLE LIVING WITH SICKLE
CELL DISEASE.
THOSE PATIENTS HAVING THEIR DATA
THAT'S BEING CAPTURED IN
ELECTRONIC HEALTH RECORDS TO BE
SUBMITTED TO THE DATA HUB.
NOW WE ARE LOOKING AT OTHER DATA
SOURCES TO CREATE A 360 DEGREE
VIEW OF PATIENTS BECAUSE
OBVIOUSLY THE ELECTRONIC HEALTH
RECORD DATA WHILE IT HAS A LOT
AND PROBABLY SOME OF THE MOST
INFORMATION ABOUT PATIENTS, IT
ALSO IS NOT 100% COMPREHENSIVE.
BUT RIGHT NOW OUR FOCUS IS
STARTING ON THE ELECTRONIC
HEALTH RECORD.
AS THOSE DATA DO COME OVER TO
US, WE THEN HAVE COMMITTEES AND
STRUCTURES THAT ARE HELPING TO
FIGURE OUT HOW DO WE BEST
ANALYZE AND MAKE THAT DATA
AVAILABLE FOR RESEARCH AS WELL
AS QUALITY IMPROVEMENT.
SO HERE YOU'LL SEE A PICTURE
THAT'S SORT OF SYNONYMOUS WITH
THE ONE THAT NICOLE SHARED WITH
YOU.
THIS ONE IDENTIFIES THE 37 SITES
THAT ARE CURRENTLY PARTICIPATING
IN THE DATA HUB.
ALL OF THESE SITES ARE ALSO
ASSOCIATED WITH THE CLINICAL
TRIALS NETWORK.
WE HAVE SENT OUT AND ARE IN THE
PROCESS OF ENROLLING OUR NEXT
20, BUT FOR THESE 30 YOU SEE
HERE, IT COVERS APPROXIMATELY
25,000 PATIENTS ACROSS ALL OF
THESE INSTITUTIONS.
AND OF THOSE THAT ARE ACTIVELY
SUBMITTING DATA ON -- AT LEAST
ON A QUARTERLY BASIS WHICH IS
REQUIRED TO, MANY HAVE SELECTED
TO SUBMIT DATA MONTHLY, WE HAVE
10,000 PATIENTS SO FAR THAT HAVE
BEEN SUBMITTED TO THE DATA HUB.
AND THE REMAINING SITES ARE
WORKING ON THEIR DATA
SUBMISSIONS AND GOING THROUGH
TEST PROCESSES.
WHILE WE ANTICIPATE THAT WHEN WE
GET THROUGH TO THE -- THANK YOU
VERY MUCH FOR THE CLAP.
WE ANTICIPATE THAT AS WE GET
THROUGH THE NEXT COUPLE OF
COHORTS THAT WE'LL BE INVITING
TO THE DATA HUB TO HAVE AT LEAST
ONE HALF OF ALL OF THE U.S.
POPULATION FOR SICKLE CELL
DISEASE, OUR INTEND INTENT IS NO
STOP THERE, OUR INTENT IS TO
HAVE A FULLY REPRESENTATIVE KAY
TA BDATABASE THAT ENCOMPASSES AR
MOST ALL OF THOSE WITH SICKLE
CELL DISEASE.
OUR DATA GOES BACK TO 2015.
WE SELECTED THAT DATE BECAUSE
THERE WERE SOME MEANINGFUL USE
MEASURES THAT WERE PUT INTO
PLACE THAT MADE IT MOST LIKELY
THAT INSTITUTIONS THAT HAVE
STARTED TO CAPTURE DATA FROM
ELECTRONIC HEALTH RECORDS IF
THEY HADN'T PRIOR.
THEY GO ALL THE WAY BACK TO
2015, CAPTURE EVERY PATIENT UP
TO THAT CURRENT DAY, AND THEN
WHEN THEY SUBMIT THE NEXT TIME
OR EVERY MONTH OR EVERY QUARTER,
WHATEVER THEY SELECT, WE THEN
GET THOSE ADDITIONAL PATIENT
EVENTS THAT HAVE OCCURRED SINCE
THEIR PRIOR SUBMISSION.
SO THAT'S WHY THIS DATABASE
ACTUALLY GROWS VERY, VERY
QUICKLY.
THIS NEXT SLIDE HERE IS
REPRESENTATIVE OF THE TYPES OF
METRICS THAT WE ARE INITIALLY
FOCUSING ON.
OUR SICKLE CELL SUBCOMMITTEE,
WHICH IS CLAIREED BY DR. ALEXIS
THOMPSON AND THERE ARE MEMBERS
WHO ARE PRESENT HERE TODAY THAT
ARE ON THAT COMMITTEE, THEY
IDENTIFY THESE METRIC AREAS
SPECIFICALLY BECAUSE, A, THEY
ARE CLINICALLY IMPORTANT, BUT
ALSO, B, WE FELT THEY HAD THE
BEST CLANBEST CHANCE OF BEING CD
USING HEALTH RECORD DATA.
WE RECOGNIZE MANY OF THESE
METRICS OR SOME OF THEM MAY NEED
TWEAKING AS WE'RE LOOKING AT
THEM NOW WITH REAL DATA BEHIND
THEM.
BUT THIS IS JUST TO GIVE YOU A
QUICK BIRD'S-EYE VIEW OF WHERE
WE'RE INITIALLY FOCUSED, BUT
CERTAINLY IT'S NOT WHERE WE'RE
STARTING AND STOPPING.
THIS IS VERSION 1 OF THE METRICS
THAT ARE AVAILABLE FOR US TO BE
ABLE TO ANALYZE AND USE FOR
RESEARCH.
FOR RESEARCH, WE CAN CREATE
OTHER METRICS AND GO BEYOND
THIS, BUT THESE ARE THE SORT OF
STANDARDIZED ONES THAT WE'RE
FOCUSED ON.
SO THE NEXT FEW SLIDES I'M GOING
TO SHARE WITH YOU SOME SCREEN
SHOTS OF WHAT OUR SITES WHO
PARTICIPATE IN THE DATA HUB HAVE
ACCESS TO.
BUT THIS SHOULD ALSO HELP YOU TO
GET A BETTER SENSE OF THE TYPE
OF DATA THAT WE HAVE, AND
QUESTIONS THAT COULD BE
ADDRESSED AND ANSWERED FOR
VARIOUS RESEARCH PURPOSES.
SO FOR EXAMPLE, THIS IS A SITE
PORTAL, SO EACH SITE THAT
SUBMITS DATA, THEY HAVE ACCESS
TO THEIR VERY OWN CONFIDENTIAL
SITE PORTAL.
THIS SCREEN SHOT HERE, YOU CAN
SEE, GOING ACROSS THE TOP, IN
THOSE LITTLE WHITE BOXES, THERE
ARE A SERIES OF FILTERS.
YOU CAN GO AND YOU CAN SELECT,
OKAY, SHOW ME ALL FEMALES OR
SHOW ME PATIENTS WHO ARE AGE 12
TO 16 AND SHOW ME GENOTYPE AND
IT WILL DRILL DOWN SO ALL OF THE
METRICS PRESENTED WILL SHOW
SPECIFICALLY THAT COHORT.
SO THIS IS THE CLINICAL
DASHBOARD.
ALSO GOING ACROSS A LITTLE BIT
BELOW THAT, YOU'LL SEE WHERE
THERE ARE DIFFERENT TABLES, SO
ONE IS THE PARTICIPANT
CHARACTERISTICS, ACUTE CARE
EVENT, PHARMACOTHERAPY,
CEREBRAL, RENAL, AND WE HAVE
SEVERAL OTHER CATEGORIES WHERE
THERE ARE A NUMBER OF DIFFERENT
METRICS THAT ARE PRESENTED.
AS YOU LOOK AT THESE GRAPHS,
YOU'LL SEE THAT THERE ARE
DIFFERENT GRAPHICAL DISPLAYS
DEPENDING WHAT THE DATA IS THAT
WE'RE LOOKING AT.
BUT THIS ONE IN PARTICULAR IS
JUST SHOWING YOU HOW RESULTS
HAVE CHANGED FROM OVER TIME, AND
THIS PARTICULAR EXAMPLE SHOWS
MAY 2019 TO THE JANUARY 2021,
AND IT'S A CONTROL CHART, SO
SITES CAN BE ABLE TO SEE HOW
THEY'RE DOING BASED ON UPPER AND
LOWER LIMITS, AND THE LIMITS ARE
NOTED THERE IN THE LEGEND
UNDERNEATH THE X LINE AND CAN BE
TURNED ON AND OFF.
ONE AREA THAT IS HIGH PRIORITY
FOR US IS FOCUSING ON DATA
QUALITY, AND WE HAVE TWO DATA
QUALITY REPORTS.
DATA QUALITY LEVEL ONE AND DATA
QUALITY LEVEL TWO.
IT'S A WHOLE TALK IN AND OF
ITSELF BUT I'LL GIVE YOU THE
HIGHLIGHTS OF IT.
SO DATA QUALITY LEVEL ONE IS
WHERE WE FOCUS ON WHEN THE DATA
SUBMITTED, DOES IT HAVE
INTEGRITY, ARE ALL THE DATA
THERE, ARE THE TABLES ORGANIZED
IN A STRUCTURED WAY.
WE ALIKE USING OMA, WE ALSO ARE
ABLE TO UT UTILIZE FIRE DATA, PE
STARTING TO TEST, BUT LOOKING AT
THE INTEGRITY OF THE DATA.
LEVEL 2, WHICH IS AN EXAMPLE
HERE, IS LOOKING AT THE
CONSISTENCY, AND IT WILL SHOW
CERTAIN METRIC RESULTS THAT WERE
IN THE PRIOR SUBMISSION COMPARED
TO THE NEW ONE.
SO IF YOU SEE THE AVERAGE
PATIENTS PER PROVIDER IS 52 ON
THAT FIRST SUBMISSION AND THEN
ALL OF A SUDDEN IT WAS 500 IN
THE SECOND SUBMISSION, THESE ARE
TO CREATE HIGHLIGHTS SO THAT THE
SITES THEMSELVES WHO OWN THESE
DATA CAN IDENTIFY IF SOMETHING
LOOKS A LITTLE OFF OR MAKE SURE
THAT IT LOOKS CORRECT.
THIS HERE IS AN EXAMPLE OF A
COHORT FINDER, SO SITES IF THEY
WANT TO BE ABLE TO DRILL DOWN
AND FIND A CERTAIN PATIENT
COHORT PERHAPS FOR A RESEARCH
STUDY, BUT ALSO PERHAPS IN
LOOKING AT POTENTIAL GUIDELINE
TREATMENTS.
FOR EXAMPLE, IN THE FUTURE,
THERE SHOULD BE AN UPDATE TO A
SICKLE CELL DISEASE GUIDELINE
THAT INDICATES PATIENTS WITH
CERTAIN CHARACTERISTICS SHOULD
BE CONSIDERED FOR A NEW THERAPY.
IN THAT CASE, THE SITE CAN COME
IN, THEY CAN DRILL DOWN,
IDENTIFY WHO THAT POTENTIAL
COHORT MIGHT BE ELIGIBLE FOR
THAT NEW THERAPY AND IT GIVES
THEM A LIST QUICKLY OF THOSE
PATIENTS WHO THEY MIGHT WANT TO
REACH OUT TO AND HAVE A
CONVERSATION WITH.
HERE IS WHERE SITES WILL BE ABLE
TO MONITOR EVERY SINGLE
SUBMISSION THEY SEND TO US.
IT SHOWS THEY'VE RECEIVED IT,
IT'S IN THE PROCESS OF BEING
UPDATED AND ONCE THAT DATA IS
AVAILABLE IN THE DATA HUB AND
LIVE IN THEIR DASHBOARD.
AND BY CLICKING ON THE DETAILS,
THERE'S MANY MORE TECHNICAL
DETAILS FOR ANYBODY WHO HAS THE
STOMACH FOR THAT SORT OF
INFORMATION.
SO WHILE SEVERAL OF OUR SITES DO
HAVE ACCESS TO THEIR OWN EHR
DATA TO USE FOR LOCAL DATA
ANALYTIC PURPOSES THAT PERHAPS
GO BEYOND WHAT OUR DASHBOARD IS
GOING TO AFFORD THEM, THEY CAN
DOWNLOAD THEIR DATA BACK OUT OF
THE DATA HUB BUT IN THE FORM OF
AN ANALYTIC DATASET SO THEY'RE
NOT GETTING THIS BIG HUGE EHR
DATA FILE, INSTEAD THEY'RE
GETTING AN ANALYTIC DATASET THAT
HAS TAKEN DIFFERENT EHR CODES
AND ORGANIZED IT IN A WAY THAT
MAKES IT EASIER TO ANALYZE.
AND THIS LAST SLIDE HERE, IS TO
SHOW YOU THAT EACH SITE ALSO CAN
ADD USERS, SO FOR EACH SITE,
THERE IS A SITE ADMINISTRATOR,
AND THEN THEY CAN ADD ADDITIONAL
PEOPLE AT THEIR INSTITUTION TO
BE ABLE TO HAVE ONE, TWO OR ALL
OF THE FEATURES THAT ARE
AVAILABLE IN THEIR SITE PORTAL.
SO FOR EXAMPLE, YOU MIGHT
WANT -- A SITE ADMINISTRATOR
MIGHT WANT TO HAVE A COMMITTEE
BE ABLE TO ACCESS THE
OVERARCHING REPORT, BUT THEY
DON'T WANT THEM TO BE ABLE TO
LOOK AT THE DATA SUBMISSIONS TAB
BECAUSE THAT'S MORE TECHNICAL.
SO IT JUST ANOTHER NICE FEATURE
TO MAKE THIS TOOL WORK FOR AS
MANY PEOPLE AS POSSIBLE AT THEIR
INSTITUTION.
SO THAT WAS A BRIEF OVERVIEW OF
WHY THE DATA EXISTS, WE'RE HERE
TO FOCUS ON SUPPORTING RESEARCH
AND QUALITY IMPROVEMENT BY USING
REAL WORLD DATA AND A OTH OTHERT
DIEDSTUDIES AS NEEDED, SO THEY N
SUPPORT THEIR OWN RESEARCH AND
QUALITY IMPROVEMENT EFFORTS AS
WELL.
SO IT'S NOW MY PLEASURE TO HAND
YOU OVER TO EMILY TUCKER, WHO'S
GOING TO TALK WITH YOU ABOUT OUR
REAL WORLD EVIDENCE INITIATIVES
THAT WE'RE WORKING ON RIGHT NOW
WITH THE FDA.
THANK YOU.
>> THANK YOU, DR. HEWITT.
THANK YOU FOR THE OPPORTUNITY TO
SPEAK AT THIS YEAR'S MEETING.
I'M SENIOR MANAGER FOR EVIDENCE
DEVELOPMENT WITH THE ASH
RESEARCH COLLABORATIVE DATA HUB.
TODAY I'LL COVER HOW WE'RE
COLLECTING REAL WORLD DATA TO
GENERATE REAL WORLD EVIDENCE IN
SUPPORT OF FDA REGULATED
RESEARCH.
SO WHAT DOES IT MEAN WHEN WE
TALK ABOUT REAL WORLD DATA AND
REAL WORLD EVIDENCE?
REAL WORLD DATA ARE THE DATA
RELATING TO PATIENT HEALTH
STATUS AND THE DELIVERY OF
HEALTHCARE ROUTINELY COLLECTED
FROM A VARIETY OF SOURCES SUCH
AS ELECTRONIC HEALTH RECORDS,
CLAIMS, AND PATIENT REGISTRIES.
REAL WORLD EVIDENCE IS THE
CLINICAL EVIDENCE REGARDING THE
USAGE AND POTENTIAL BENEFITS
ORIS BEINGS OF THE MEDICAL
PRODUCT DERIVED FROM THE
ANALYSIS OF REAL WORLD DATA.
REAL WORLD EVIDENCE CAN BE
GENERATED BY DIFFERENT STUDY
DESIGNS OR ANALYSES SUCH AS
RANDOMIZED AND PRAGMATIC TRIALS
AND OBSERVATIONAL STUDIES.
SO WHY ARE THESE DEFINITIONS
IMPORTANT?
THE DATA HUB IS A MODERN
PLATFORM THAT FACILITATES THE
ACQUISITION -- TO CREATE
RESEARCH GRADE DATA ASSETS AS
WELL AS ASSESSING OUTCOMES TO
ENHANCE CARE IN HEMATOLOGY.
AT THIS TIME, WE ARE PRIMARILY
COLLECTING ELECTRONIC HEALTH
RECORD DATA BUT DO HAVE PLANS TO
COLLECT GENOMIC DATA,
PATIENT-REPORTED OUTCOMES AND
CLAIMS DATA.
OUR PROGRAM LEVERAGES RECENT
HEALTH IT REGULATORY CHANGES AND
INTEROPERABILITY ENHANCEMENTS TO
MAKE IT EASIER AND MORE
CONSISTENT WITH CLINICAL SITES
TO PARTICIPATE.
AS YOU CAN SEE HERE, WE INTEND
TO SUPPORT A NUMBER OF DIFFERENT
STAKEHOLDERS SUCH AS OUR PATIENT
AND COMMUNITY MEMBERS,
CLINICIANS, RESEARCHERS, AND
FEDERAL ENTITIES.
SO WHY ARE WE FOCUSING ON REAL
WORLD DATA?
I THINK WE CAN ALL AGREE THAT
RANDOMIZED CONTROL TRIALS ARE
THE PREFERRED SOURCE OF EVIDENCE
WHEN IT COMES TO THE
EFFECTIVENESS OF INTERVENTIONS
BUT I THINK WE CAN ALSO AGREE
THAT THEY ARE NOT REPRESENTATIVE
OF THE GENERAL POPULATION ORTHOS
WITH A PARTICULAR DISEASE.
WHILE THEY ARE A KEY RESEARCH
TOOL FOR ADVANCING KNOWLEDGE AND
CARE FOLLOW UP IS LIMITED,
STUDIES ARE INCREDIBLY EXPENSIVE
AND IT TAKES A SIGNIFICANT
AMOUNT OF TIME TO ENROLL AND
MAINTAIN PATIENTS.
THIS IS WHERE REAL WORLD DATA
COMES IN, TO AUGMENT, NOT TO
REPLACE, HOW WE'RE CONDUCTING
CLINICAL RESEARCH.
REAL WORLD DATA CAN BE COLLECTED
FROM ANY NUMBER OF COHORTS OR
POPULATION SHOULD BE GROUPS
ALONG WITH THE EXAMINATION OF
NEW TREATMENTS IN REAL WORLD
SETTINGS WHERE PATIENTS'
BEHAVIOR, CONCURRENT TREATMENTS
AND ENVIRONMENTAL FACTORS ARE
NOT INFLUENCED BY PARTICIPATION
IN A CLINICAL TRIAL.
BY LEVERAGING THE DATA THAT'S
ALREADY BEING CAPTURED ROUTINELY
IN HEALTHCARE, WE'RE ABLE TO
ASSESS THE IMPACT OF
INTERVENTIONS, CHARACTERIZE
HEALTH CONDITION, AND PATIENT
OUTCOMES, AND IDENTIFY AND
ADDRESS HEALTH INEQUITIES, ALL
AT A MUCH LOWER COST.
NOW, CAPTURING REAL WORLD DATA
IS GREAT, BUT IT ISN'T ENOUGH.
WE NEED TO GENERATE EVIDENCE TO
ENSURE THESE OUTCOMES COME TO
FRUITION.
IN THE DRAFT GUIDANCE FDA SHARED
AROUND THIS TIME LAST YEAR, THE
AGENCY FOCUSED ON THREE CHAL
EX-RELATED TO THE USE OF REAL
WORLD DATA GATHERED FROM
ELECTRONIC HEALTH RECORDS AND
CLAIMS.
INCLUDING THE SELECTION OF DATA
SOURCES THAT APPROPRIATELY
ADDRESS THE STUDY QUESTION,
DEVELOPMENT AND VALIDATION OF
DEFINITIONS FOR STUDY DESIGN
ELEMENTS, AND DATA PROVENANCE
AND QUALITY THROUGHOUT THE
LIFECYCLE.
IT'S IMPORTANT TO BE COGNIZANT
OF THESE TYPES OF INHERENT
CHALLENGES WHEN USING SUCH DATA
IN RESEARCH, WHICH IS WHY WE'VE
BEEN WORKING TOWARDS DEVELOPING
IMPROVED APPROACHES TO GENERATE
VALID EVIDENCE.
FDA'S GUIDANCE MADE IT CLEAR
THAT THE STRENGTH OF REAL WORLD
EVIDENCE ES PISHLY IN SUPPORT OF
A REAL WORLD DECISION IS
DEPENDENT UPON THE METHODOLOGY,
RELIABILITY AND EVIDENCE OF THE
UNDERLYING DATA.
UNDERSTANDING AND MANAGING THE
QUALITY OF THE OVERALL DATA IS
AMBITIOUS, WHICH IS WHY WE
DEVELOPED A STRATEGY TO SUPPORT
THE CREATION OF A KR A COMPREHEE
HIGH QUALITY DATASET.
FOLLOWING ARE CONSIDERATIONS FOR
OUR DATA QUALITY STRATEGY.
THE FIRST IS RELEVANCE.
DATA SHOULD BE RELEVANT NOT ONLY
TO THE SITE AND THE PHYSICIAN TO
ENABLE CONTINUED PARTICIPATION
IN THE PROGRAM, BUT ALSO TO
THOSE WHO INTEND TO LEVERAGE THE
DATA, SUCH AS RESEARCHERS AND
THE FDA.
NEXT IS TIMELINESS.
IT'S IMPERATIVE STAKEHOLDERS
HAVE -- SUBMIT THEIR DATA ON A
WEEKLY, MONTHLY OR QUARTERLY
SCHEDULE.
THE THIRD IS COMPLETENESS,
REQUIRING THAT RECORDS BE
SELECTED WITHOUT GAPS OR
DUPLICATIVE DATA.
VALIDITY, A LIST OF RULES,
REQUIREMENTS AND DEFINITIONS.
AND LASTLY, CONSISTENCY.
RECORDS MUST BE ACCURATE AND
DETAILED FOR ENABLING WELL
THOUGHT DECISION-MAKING, DATA
CONSISTENCY ENSURES THAT
ANALYTICS CORRECTLY CAPTURE AND
RENCH THE VALUE OF THE DATA.
WE INTEND TO CONTINUE TO EXPLORE
STRATEGIES FOR FILLING GAPS IN
DATA THAT MAY BE DIFFICULT TO
OBTAIN FROM ELECTRONIC HEALTH
RECORDS.
INCLUDING THE USE OF MOBILE
TECHNOLOGIES, PATIENT-REPORTED
OUTCOMES, WEARABLES AND LINKING
TO EXTERNAL DATABASES TO CREATE
A MORE COMPREHENSIVE PICTURE OF
PATIENT CARE.
HERE IS JUST ONE EXAMPLE OF HOW
WE ARE CONTINUING TO FOCUS ON
MINIMIZING THE DATA CAPTURE
BURDEN WHILE CONTINUING TO
ADDRESS DATA TA QUALITY.
QUALITY.
THE DATA WE COLLECT IS
TRANSFERRED ON A MONTHLY OR
QUARTERLY BASIS AS I MENTIONED
EARLIER.
WE THEN PERFORM A DATA QUALITY
ASSESSMENT TO IDENTIFY ANY
ANOMALIES OR MISSING DATA THAT
MAY EXIST IN THE SUBMISSION AND
GENERATE A PRE-POPULATED
ELECTRONIC CASE REPORT THE SITE
CAN REVIEW.
THE SITE CAN THEN EASILY ADDRESS
ANY DISCREPANCIES OR MISSING
DATA AND RESUBMIT.
ONCE THIS INFORMATION IS
RECEIVED, THE DATA HUB NOW
BECOMES A SOURCE OF TRUTH AND
THE UPDATED DATA WILL APPEAR ON
THE DASHBOARD WHERE THEY CAN
COMPARE OUTCOMES TO THE
AGGREGATE OF THOSE PARTICIPATING
IN THE DATA HUB.
WHILE THERE'S STILL SOME ELEMENT
OF MANUAL CURATION, WE'RE ABLE
TO ALLEVIATE THE MAJORITY OF
THAT EFFORT, LEVERAGING WHAT
ALREADY LIVES IN A PATIENT'S
HEALTH RECORD.
TO AUGMENT OUR EFFORTS IN
GENERATING REAL WORLD EVIDENCE,
WE TEAMED UP WITH THE INNOVATIVE
GENOMICS INSTITUTE IN
COLLABORATION WITH THE FDA AND
HOSTED TWO STAKEHOLDER
ROUNDTABLE MEETINGS TO
ACCELERATE INNOVATIONS FOR
SICKLE CELL DISEASE WITH REAL
WORLD EVIDENCE, WHICH WE OFTEN
REFER TO AS THE RWE INITIATIVE.
THE PURPOSE WAS TO EXPLORE A
NATIONWIDE REAL WORLD DATA
SYSTEM TO GENERATE EVIDENCE
FOFER CLINICAL STUDIES REGULATED
BY THE FDA.
IN ORDER TO ACCOMPLISH THIS, WE
LAUNCHED TWO WORKING GROUPS
FOCUSED ON GENOMIC THERAPIES AND
COORDINATED REGISTRY NETWORKS.
THE GENOMIC THERAPIES WORKING
GROUP SOUGHT TO IDENTIFY DATA
POINTS THAT SHOULD BE COLLECTED
TO GENERATE ACTIONABLE,
REGULATORY GRADE REAL WORLD
EVIDENCE FOR GENOMIC THERAPIES
IN SICKLE CELL DISEASE.
TO MINIMIZE THESE RISKS AND SET
THE BROADER FIELD FOR LONG TERM
SUCCESS, COORDINATED EFFORTS
HELPED IDENTIFY TO ADDRESS
UNANSWERED QUESTIONS AROUND
SAFETY AND EFFICACY OF THESE
THERAPIES, CREATING THE
OPPORTUNITIES FOR THE DATA
GENERATED TO IMPACT REGULATORY
DECISION-MAKING AND ENABLE
IMPROVEMENTS IN THERAPEUTIC
DESIGN AND RISK MANAGEMENT.
THE COORDINATED REGISTRY NETWORK
WORKING GROUP AIMED TO DISCUSS
THE ROLE OF COORDINATED REGISTRY
NETWORKS FOR PATIENT LEVEL DATA
AGGREGATION BY LINKING
TRADITIONAL CLINICAL REGISTRIES
TO OTHER DATA SOURCES.
COORDINATED REGISTRY NETWORKS
HAVE THE POTENTIAL TO IMPROVE
CARE BY BRINGING TOGETHER DATA
FROM MULTIPLE SOURCES RESULTING
IN A MORE HOLISTIC,
COMPREHENSIVE AND COST-EFFECTIVE
APPROACH TO GENERATING REAL
WORLD EVIDENCE.
BOTH WORKING GROUPS INCLUDED A
DIVERSE GROUP OF STAKEHOLDERS
INCLUDING FEDERAL ENTITY,
SCIENTISTS, PAYERS, SICKLE CELL
DISEASE COMMUNITY MEMBERS AND
INDUSTRY.
BY INCLUDING SO MANY DIFFERENT
GROUPS WE WERE ABLE TO GATHER
THE NEEDS EACH BROUGHT TO THE
TABLE WHICH RESULTED IN THE
CREATION OF TWO REPORTS WHICH
WILL BE HELPFUL IN GUIDING THE
DATA HUBS KEY TECHNOLOGY AND
INFRASTRUCTURE NEEDS AS WE
CONTINUE TO DEVELOP AND GROW THE
PROGRAM.
LASTLY THE REPORTS I JUST
TOUCHED ON PRODUCED IN THE
INITIATIVE WILL BE AVAILABLE FOR
OPEN COMMENT THIS FALL, WHERE WE
HOPE TO RECEIVE VALUABLE
FEEDBACK FROM MANY KEY
STAKEHOLDERS INCLUDING THE
GENERAL PUBLIC.
AND WITH THAT, I WILL PASS
THINGS OVER TO DR.' LEXIS
THOMPSON, CHIEF OF THE DIVISION
OF HEMATOLOGY AT CHILDREN'S
HOSPITAL OF PHILADELPHIA AND
CHAIR OF OUR SICKLE CELL DISEASE
SUBCOMMITTEE.
THANK YOU.
>> GOOD AFTERNOON OR GOOD
MORNING FOR MY FRIENDS ON THE
WEST COAST.
IT'S REALLY A PRIVILEGE TO BE A
PART OF THIS PRESENTATION TODAY
WITH MY COLLEAGUES FROM ASH, AS
WELL AS FRIENDS AND COMPLETION
BROADLY IN THE SICKLE CELL
COMMUNITY.
I'M GOING TO BE COVERING BRIEFLY
THE SICKLE CELL LEARNING
COMMUNITY, AND THIS IS A CONCEPT
THAT'S NEW TO INDIVIDUALS, I
JUST WANT TO SHARE SOME CONTEXT.
THE LEARNING COMMUNITIES WERE
INITIALLY CALLED LEARNING
HEALTHCARE SYSTEMS, AND THIS WAS
INITIALLY ADVOCATED, THIS IDEA
CAME ABOUT FROM THE NATIONAL
ACADEMIES OF MEDICINE IN 2007,
AND SPECIFICALLY THESE LEARNING
HEALTH SYSTEMS WERE INTENDED TO
ADVANCE SCIENCE INFORMATICS
INCENTIVES AND CULTURE ALIGNED
FOR CONTINUOUS IMPROVEMENT AND
INNOVATION.
WITH BEST PRACTICES SEAMLESSLY
EMBEDDED IN A DELIVERY SYSTEM,
AND SPECIFICALLY WITH PATIENT
AND FAMILIES AS ACTIVE
PARTICIPANTS IN ALL ELEMENTS.
SO THE MULTI-STAKEHOLDER TEAMS
FOR THE SICKLE CELL LEARNING
COMMUNITY INCLUDE NOT ONLY
PATIENTS AND THEIR FAMILIES BUT
ALSO HEMATOLOGISTS, BOTH
PEDIATRIC AND ADULT
HEMATOLOGIST, ALLIED HEALTH
PROFESSIONALS, RESEARCHERS,
IMPLEMENTATION SCIENTISTS, WHO
HAVE ALL COME TOGETHER TO
IDENTIFY COMMON GOALS AND SELECT
IMPROVEMENT AREAS.
WE'VE ESTABLISHED WORKING GROUPS
THAT HAVE PUT TOGETHER CHANGE
PACKAGE, AND WE'LL BE ABLE TO
MEASURE CHANGE ULTIMATELY, AT
LEAST AT THE PATIENT LEVEL,
USING DATA THAT'S IN THE DATA
HUB.
NOW THIS WILL BE THE VERY FIRST
TIME THAT A LEARNING COMMUNITY
HAS BEEN ESTABLISHED WITH SICKLE
CELL DISEASE AT ITS CORE.
SOME OF YOU IN ACADEMIC
INSTITUTIONS MAY BE FAMILIAR
WITH OTHER LEARNING HEALTH
NETWORKS OR LEARNING COMMUNITIES
THAT HAVE BEEN ESTABLISHED TO
ADDRESS AND IMPROVE OUTCOMES FOR
PATIENTS WITH HEART FAILURE,
CYSTIC FIBROSIS, WITH
INFLAMMATORY BOWEL DISEASE, MANY
OF WHICH HAVE HAD SOME
REMARKABLE SUCCESS OVER THE LAST
10 TO 12 YEARS.
THE LEARNING COMMUNITY FOR
SICKLE CELL DISEASE HAS SELECTED
AS ITS PRIMARY PURPOSE TO
IMPROVE THE CARE AND OUTCOMES OF
PEOPLE LIVING WITH SICKLE CELL
DISEASE.
WE'RE GOING TO ACCOMPLISH THAT
BY USING DATA TO IDENTIFY QI
OPPORTUNITIES, AND WE'VE ALREADY
STARTED BY LAUNCHING PILOT
LEARNING COMMUNITY SITES AT
ABOUT 10 TO 20 OF THE SITES THAT
ARE ALIGNED WITHIN THE ASH RC
SITES THAT HAVE BEEN DESCRIBED
JUST A FEW MOMENTS AGO.
THESE ACTUALLY ARE SOME OF THE
SITES THAT JUST HAVE ELECTED TO
BECOME PART OF OUR PILOT SITES.
THEY ARE A SUBSET OF THE SITES
THAT ARE A PART OF THE ASH RC,
AND ALSO SOME WHO ARE ONBOARDING
INTO THE DATA HUB.
AND SO AMONG THESE SITES, THEY
INCLUDE ALMOST AN EQUAL BALANCE
BETWEEN PEDIATRIC AND ADULT
PATIENTS.
THEY REPRESENT ABOUT 10,000
SICKLE CELL PATIENTS, AND THEY
ARE CURRENTLY IMPLEMENTING QI
PROJECT, WHICH I'LL DESCRIBE FOR
YOU.
WE HAD A DESIGN WORK GROUP AND
WE HAVE BEEN MAINTAINING A
TECHNICAL ADVISORY GROUP THAT
HAVE HELPED US TO ACTUALLY
FORMULATE A GLOBAL AIM, WHICH IS
TO PROFOUNDLY IMPROVE THE LIFE
COURSE AND QUALITY OF LIFE OF
INDIVIDUALS LIVING WITH SICKLE
CELL DISEASE.
THIS TEAM, THROUGH AN ITERATIVE
PROCESS, HAVE IDENTIFIED TWO QI
GOALS.
THESE WILL NOT BE THEIR LAST
GOALS BUT CERTAINLY THE FIRST
TWO.
THE FIRST, WHICH ALL PILOTS THEY
PARTICIPATE IN, IS TO IMPROVE
THE RELIABLE USE OF DISEASE
MODIFYING THERAPY, AND THIS
INCLUDES, OF COURSE, HURRICANE
HYDROXYUREA.
SOME MY PAI LOT SITES WILL HAVE
A SECOND QI PROJECT WHICH WILL
IMPROVE THE USE OF CODEVELOPED
PAIN MANAGEMENT PLANS, WHICH
MEANS CODEVELOP WITH THE PATIENT
AND THEIR PROVIDER.
THESE TEAMS HAVE ACTUALLY COME
TOGETHER FROM THE PILOT SITES
AND HAVE PUT TOGETHER A TOOLKIT
WHICH CONTINUES TO GROW, AND
RESIDES IN THE ASH COMMUNITY'S
WEBPAGES.
THE QI TOOLS HAVE INCLUDED THOSE
THAT INCLUDE THINGS LIKE THEIR
PAIN ACTION PLANS FROM VARIOUS
SITES, MATERIALS THAT SITES ARE
USING FOR PATIENT EDUCATION
AROUND DISEASE HOD GUYING
THERAPIES, PROCESS MAPS THAT
SOME OF THE TEAMS HAVE DEVELOPED
IN TERMS OF DECIDING HOW
PATIENTS ARE ENGAGED AND HOW
THEY CONSIDER THE USE OF, FOR
INSTANCE, DISEASE MODIFYING
THERAPIES, WHEN ARE THEY
INTRODUCED, WHO DOES THAT, WHAT
IS THE PROCESS AND HOW
FREQUENTLY ARE THESE THINGS
RE-ASSESSED AT
EACH ONE OF THE SITES.
SO IT HAS PROVIDED AN AMAZING
OPPORTUNITY FOR ALL OF THE PILOT
SITES TO WORK TOGETHER ON
MONTHLY ACTION PERIODICALS TO
LOOK AT PROGRESS THAT THEY'RE
MAKING AND DECIDING AT EACH SITE
HOW THEY WILL CHOOSE TO ONBOARD
THESE TWO INITIATIVES.
I SHOULD ALSO MENTION WHILE THIS
EFFORT HAS LARGELY BEEN
SUPPORTED BY THE AMERICAN
SOCIETY OF HEMATOLOGY, WE HAVE
BEEN GRATEFUL FOR A SUPPORT FOR
A GRANT FROM THE DEPARTMENT OF
HEALTH AND HUMAN SERVICES.
YEAR ONE HAD BEEN ABOUT THE
DEVELOPMENT AND DESIGN OF THE
LEARNING COMMUNITY AND
FACILITATING INCREASED
PARTICIPATION, THE DATA HUB.
YEAR TWO, WHICH WE ARE CURRENTLY
IN, IS ABOUT IMPLEMENTATION, AND
SO THAT IS WHY DURING THIS YEAR,
WE ARE FOCUSING ON GETTING THE
PILOT SITES TO ACTUALLY BEGIN
THE WORK OF CREATING THE CHANGE
PACKAGE THAT WE HOPE TO ACTUALLY
EVENTUALLY SEE ACROSS THE ENTIRE
SET OF INSTITUTIONS THAT ARE
PART OF THE LEARNING COMMUNITY,
AND ULTIMATELY IN YEAR THREE, WE
WILL BEGIN A NATIONWIDE
IMPLEMENTATION AND THAT WILL
BEGIN IN OCTOBER OF THIS YEAR.
FOR THE FIRST TIME, THIS HAS
OBVIOUSLY BEEN IMPACTED BY THE
PANDEMIC, WE WILL HAVE AN
IN-PERSON LEARNING COMMUNITY
MEETING IN LATE SEPTEMBER.
WE'RE LOOKING FORWARD TO HAVING
LESSONS LEARNED FROM ALL OF OUR
SITES THAT ARE PARTICIPATE, AND
TO REALLY LOOK FOR THE
OPPORTUNITIES TO BEGIN ALSO
LOOKING AT SUSTAINABILITY AND
SCALABILITY OF OUR EFFORTS.
SO WITH THAT, I'M GOING TO TURN
THIS BACK OVER TO DR. ABRAMS TO
SUMMARIZE.
THANK YOU.
>> NEXT SLIDE.
THANK YOU.
SO AS YOU CAN SEE, WE'RE ON A
WAVE AND PLANNING ON RIDING THIS
WAVE.
THERE'S BEEN TREMENDOUS
MOMENTUM, THERE'S BEEN INTEREST,
THERE'S BEEN INVESTING,
INVESTMENT IN MAKING THIS WORK.
SO WE'RE LOOKING FORWARD TO
VALVE NIEZING FORCES AND
GALVANIZING FORCES WITH ALL OF
YOU INVOLVED ON THIS CALL.
I THINK IF WE CAN HARNESS THE
ENERGY AND THE INTEREST THAT
I'VE SEEN AT THIS MEETING, AND I
KNOW IS HERE TODAY, IT WILL BE
TERRIFIC.
WE'RE WELCOMING YOU TO REACH OUT
TO US WITH COLLABORATIONS OR
IDEAS, AND I'LL DIRECT YOU TO
OUR CONTACT INFORMATION, WHICH
IS SHOWN AT THE LEFT LOWER
PORTION OF THE SLIDE,
INFO@ASHRC.ORG.
THIS IS HOW COLLECTIVELY WE'RE
GOING TO BE ABLE TO MAKE A
DIFFERENCE WITH THIS DISEASE,
AND I WOULD LOVE FOR YOU TO
PERSONALLY REACH OUT TO ME SO
THAT WE CAN WORK TOGETHER.
SO WITH THAT, I'M GOING TO WRAP
UP.
I'D BE HAPPY TO TAKE ANY
QUESTIONS YOU HAVE OR MAYBE
DIRECT THEM TOWARDS MY
COLLEAGUES HERE.
SO WE'RE BACK AND STARTING WITH
SYMPOSIUM 4.
WE'RE GOING TO START WITH
DR. RIVERS.
THE ABNORMAL PRESENCE OF
MITOCHONDRIA IN SERBING LATING
RED BLOOD CELLS S WITH STRESS
ERYTHROPOISE IS IN MOUSE MODEL.
>>I'M FROM OAKLAND CALIFORNIA
AND WE SAID THE NAME OF MY TALK
SO I'LL GET INTO IT.
IT'S GOING TO BE A 15 MINUTE
TALK VERSUS A 30 MINUTE TALK SO
I WANT TO GIVE EVERYONE THE
HEADS UP.
IN 2017 MY GROUP AT THE
UNIVERSITY OF ILLINOIS-CHICAGO
IN MY LABORATORY WERE FIRST TO
PUBLISH A CASE SERIES OF SIX
PATIENTS WHERE WE DESCRIBE THE
MITOCHONDRIAL RETENTION IN
SICKLE CELL DISEASE AND WE
SHOWED IN THE SIX PATIENTS THEY
HAD A HIGHER NUMBER ERYTHROCYTES
AND YOU CAN SEE IN THE UPPER
LEFT YOU SEE REFIX RED BLOOD
CELL AND REFIX WITH
MITOCHONDRIA.
THERE'S A SIGNIFICANT DIFFERENCE
BETWEEN CONTROLS AND PEOPLE WITH
HEMOGLOBIN SS.
SO WHY WOULD THIS BE AN ISSUE
HAVING MITOCHONDRIA RETAINED IN
RED BLOOD CELLS.
USUALLY MITOCHONDRIA ROOT
BETWEEN THE RETIC AND RED BLOOD
CELLS AND FOR SICKLE CELL
PATIENTS THIS COULD BE A PROBLEM
BECAUSE MITOCHONDRIA CONSUME
OXYGEN TO MAKE ATP CAN MAKE IT
HYPOXIC AND SICKLY AND INCREASE
ROS GENERATION WHICH WE FURTHER
EVALUATED THIS IN A GROUP OF
HEMOGLOBIN SS PATIENTS AND SC
VARIANT PATIENTS.
WHAT WE SAW WAS THAT SS PATIENTS
HAD A VARIETY MUCH LEVELS OF
INCREASED RED BLOOD CELL
MITOCHONDRIA IN PANEL A AND A
VARIETY OF LEVELS OF INCREASED
ROS.
PATIENTS WERE ELEVATED BUT NOT
TO THE AMOUNT OF EXCESS
PATIENTS.
WHEN WE LOOKED AT ALL PERIPHERAL
RED BLOOD CELLS THERE'S AN
INCREASE IN SS AND A LITTLE BIT
OF SC AND THIS WAS ALREADY
KNOWN.
BUT WHAT WASN'T KNOWN AT THE
TIME WAS PANEL D THAT THE RED
BLOOD CELLS WITH MITOCHONDRIA
CONTAINED MORE ROS THAN THE RED
BLOOD CELLS WITHOUT MITOCHONDRIA
AND IN THIS ONE WE'RE USING DCSF
AS OUR STAIN AND CD71 WHICH
STAINS SIMILAR TO ORANGE AND
CONTINUING TO USE TERN TO LOOK
AT MITOCHONDRIA.
SO WHEN WE LOOKED AT HEMOLYSIS
WE SEE A CORRELATION BETWEEN
BILIRUBIN MARKERS WE DIDN'T SEE
IN PATIENTS WITH HIGH DROXIA AND
WE WANTED TO EVALUATE THE
DIFFERENCE IN MITOCHONDRIAL
RETENTION BETWEEN THE LEVELS OF
CONTROL SICKLE CELL AND
ERYTHROPOIESIS AND WE WANTED TO
EVALUATE DIFFERENCES IN THE
OXYGEN CONSUMPTION RATE OF
CONTROL SICKLE CELL DISEASE AND
STRESSOR ERYTHROPOIESIS MODEL
AND CREATED A MODEL BY
PHLEBO
PHLEBOTOMYZING AND COLLECTED
BLOOD SAMPLES ON THE FIFTH DAY.
WE DID THE RETENTION ASSAYS OF
THE PERIPHERAL BLOOD AND
INDUCTION WITH THE PHLEBOTOMY
AND COLLECT FROM THE ORBITAL
SIGN -- SINUS AND IF YOU LOOK
IN THE BLUE THE UPPER LEFT
QUADRANTS THERE'S INCREASED
PHLEBOTOMY OF ERYTHROCYTES WITH
MITOCHONDRIA WITH CONTROL NOT AS
MUCH AS SICKLE CELL DISEASE AND
INCREASED COMPARED TO CONTROL
BUT NOT AS MUCH AS HEMOGLOBIN
SS.
WE WERE ABLE TO INCREASE THIS BY
PHLEBOTOMY.
NEXT WE LOOK AT ROS AND
PHLEBOTOMY AND CONTROL HAVE THE
MOST THEY HAVE RED BLOOD CELLS
WITHOUT MITOCHONDRIA WHERE
SICKLE CELL HAS THE MOST CLOSELY
FOLLOWED BY RED BLOOD CELLS
WITHOUT MITOCHONDRIA WHICH AND
IN THE RED IS RED BLOOD CELL
WITH MITOCHONDRIA BUT THE LEFT
SIDE IS TO SHOW YOU INDEPENDENT
OF WHERE YOUR RED BLOOD CELLS
WITH MITOCHONDRIA COME FROM THEY
HAVE A SIMILAR AMOUNT OF ROS AND
YOU CAN SEE THAT IN THE GRAPH
WHICH BASICALLY SHOW THAT RETI
TEND TO HAVE MORE ROS THAN RBCs
WITHOUT MITOCHONDRIA OR RETICES
WITHOUT MITOCHONDRIA AND THE
DETERMINING FACTOR IS WHETHER
YOU HAVE HEME GLOBIN S.
AND NEXT WE WANTED TO DO A
PRECURSOR EVALUATION TO SEE IF
WE CAN SEE WHERE THE DEFECT WAS
OCCURRING AND WHEN ROS WAS
INCREASED.
SO WE FLUSHED THE BONE MARROW
FROM THE THREE GROUPS AND
STAINED THEM WITH THE PRE CUSSER
MARKER CD45 -- PRECURSOR MARKER
CD45 WITH A METHOD FROM 2013 AND
STAINING THE CD-45 VERSUS SIDE
SCATTER AND CREATED PATTERNS TO
USE OUR SORTER AND WERE ABLE TO
CREATE FIVE DIFFERENT SUBGROUPS
OR SEPARATE OUT THE BASIL
PHILICS AND RETICULOCYTES AND
SEPARATED THEM BY FLOW CYTOMETRY
FOR ROS.
THIS IS THE PATTERN YOU GET WHEN
YOU DO THE CD 44 VERSUS FORWARD
SIDE SPLATTER AND WE SAW IN
GENERAL AN INCREASE IN
PRECURSORS FROM 1 TO 6.
SOMETIMES SIGNIFICANT AND
SOMETIMES NOT UNTIL WE GOT TO
THE RED BLOOD CELLS AND THAT WAS
BECAUSE IN SICKLE CELL WE ARE
HEMOLIES -- HEMOLYZING AND IT
DECREASED OVER THE POPULATION
SIZE FROM STAGE 1 TO THE RED
BLOOD CELL IT BECAME SMALLER OR
DECREASED AND THEN THERE WAS A
CONTROL IN PHLEBOTOMY AT THE SS
RED BLOOD CELL STAGE WE SAW IN
SS.
THEN WE LOOKED AT MITOCHONDRIAL
FLUORESCENCE AND WE COULD SEE
THE SAME PATTERNS THE
MITOCHONDRIAL FLUORESCENCE WAS
DECREASING OVER TIME WITH AN
INCREASE AT STAGE 6 THE RED
BLOOD CELL STAGE.
NEXT WE WERE INTERESTED IN
LOOKING AT OXYGEN CONSUMPTION.
TO LOOK AT OXYGEN CONSUMPTION WE
LOOKED AT PERIPHERAL BLOOD AND
USED THE XE EXTRA CELLULAR FLUX
ANALYZER WHICH HAS THREE
INJECTIONS ONE IS OLIGO MYOCIN
AND THE NEXT IS SEP WHICH BLOCKS
THE FLOW OF THE ELECTRON
TRANSPORT CHAIN AND THAT ALLOWS
YOU TO MEASURE MAXIMAL
RESPIRATIONS AND THE NEXT
POISONS THE MITOCHONDRIA.
THAT ALLOWS YOU TO LOOK AT THE
NON-MITOCHONDRIAL OXYGEN
CONSUMPTION.
WE DID THIS IN A SERIES IN HUMAN
AND MOUSE INITIALLY AND WHAT WE
SAW WAS THAT IN BOTH HUMANS AND
IN MOUSE THE SICKLE CELL WAS
HIGHER IN BASAL OXYGEN
CONSUMPTION.
WHEN WE LOOKED AT THE
PHLEBOTOMIZED MOUSE WE SAW IT IN
RED BLOOD CELLS.
POSSIBLY BECAUSE THEY HAD
MITOCHONDRIA.
IN CONCLUSION THEY CONTAIN
LEVELS SIMILAR TO SICKLE CELL
MICE AND INTENSITY GOES TO THE
BONE MARROW AS WELL AS
MITOCHONDRIA THEMSELVES AND
SEEMED THE MITOCHONDRIAL OCCURS
DURING PRECURSOR AT THE RETICULA
SITE AND MOUSE HAD INCREASED
OXYGEN SIMILAR TO SICKLE CELL
DISEASE MICE LEADING US BACK TO
THE PICTURE WHERE WE SHOW
HEMOGLOBIN CAUSES SICKLING AND
EVOLYSIS AND THEY DON'T HAVE
SICK LING AND THEY DO HAVE THE
ROS GENERATION THE QUESTION IS
DID THE ROS GENERATE ENOUGH TO
LEAD TO HEHEMOLYSIS AND THEN WE
LOOKED AT THE EFFECT TO ALLOW US
TO EVALUATE THIS MODEL AND
UNDERSTAND WHAT MITOCHONDRIA
EFFECTED RED BLOOD CELL IS EVEN
BETTER.
SO THE NEXT STEPS WE WANT TO
FURTHER INVESTIGATE THE DEFECTS
IN SICKLE CELL DISEASE AND
RECENTLY A PAPER CAME OUT THAT
SHOWED DEFICIENCY PATHWAYS IN
SICKLE CELL DISEASE AND
DECREASED IN PINK IN NIK WAS
SEEN AND WE ALSO SAW INCREASES
IN ATG WITH LSD1 INHIBITION IN
OUR ORIGINAL PAPER.
WE WANT TO INVESTIGATE MYOPHAGE
INDUCING AGENTS AND ARGINNINE
AND ENDARI HAS BEEN SHOWN TO
EFFECT SICKLE CELL DISEASE AND
THERE'S A FASCINATING MECHANISM
THAT HELP IF YOU CONSIDER
THEY'RE ELECTRONIC TRANSPORT
CHAINS INSIDE THE RED BLOOD CELL
AND NOT JUST DOING GLYCOLYSIS
AND IN AN ARTICLE HAS TO
INCREASE RBC VIABILITY.
WE TALKED ABOUT MITOCHONDRIA IN
SICKLE CELL DISEASE AND
GLUTAMINE SICKLE CELL DISEASE.
AND I WANT TO MENTION AT THE END
NOT ONLY DOES MITOCHONDRIAL
INCREASE DEPLETE ROS GENERATION
AND SHOWN TO INCREASE RBC AFFECT
AND IT'S A PROINFLAMMATORY
BECAUSE OF THE HYPOME METMETMET
DNA AND THERE'S FURTHER
MECHANISMS TO TREAT
MITOCHONDRIAL DNA.
SO I WANT TO THANK THE PEOPLE IN
MY LAB.
HART HORNEMAN AND MIKAIL
ALEJANDRO AND THOSE FROM THE
UNIVERSITY OF ILLINOIS WHO
CONTINUE TO SUPPORT ME AND A
WOULD ALSO LIKE TO THANK NIH FOR
THEIR CONTINUED SUPPORT FOR THE
RECENT DIVERSITY PLATFORM.
ANY QUESTIONS?
>> THANK YOU, DR. RIVERS.
I DON'T SEE ANYTHING IN THE
CHAT.
THERE'S ONE SAYING
CONGRATULATIONS.
BEAUTIFUL AND ELEGANT WORK.
IT HAS APPLICATIONS IN SICKLE
CELL DISEASE AND NON-SICKLE CELL
CONDITIONS.
THERE'S A QUESTION FROM SUSAN.
>> IT SAYS HOW DOES THE
INHIBITOR IMPACT THIS.
OUR FIRST PAPER WE WERE LOOKING
AT LSD1 INHIBITERS TO INDUCE
HEMOGLOBIN F AND THEY DO THIS BY
INDUCING ATG5 AND ATG7.
>>
>> THEY'LL BE PRESENTING IMPACT
OF ARGININE TOMORROW AT NOON IT
WILL BE INTERESTING TO LOOK AT
THE FUNCTION IN RED BLOOD CELLS.
>> AND THERE'S A COMMENT ABOUT
SICKLE CELL.
MAY YOU COMMENT?
SO HOW DO MITOCHONDRIA AND
SICKLE CELL DISEASE -- MALARIA.
ONE INTERESTING THING AND THIS
COULD BE WITH HEMOGLOBIN S HAVE
YOU INCREASED REACTIVE OXYGEN
SPECIES INSIDE THE CELL AND MAY
BE INHOSPITABLE TO THE MALARIA
WITH THE OXYGEN ALREADY
INCREASED MITOCHONDRIA.
>> AND YOU ANSWERED THE QUESTION
HOW DID YOUR INHIBITORS AFFECT
THIS.
>> POSSIBLE STORAGE OF LEGIONS
OF RBC.
IF YOU LOOK AT THE NORMAL IN THE
GRAPH RETICS HAVE EIGHT OF
MITOCHONDRIA IN THEM REGARDLESS
OF AARSS BUT MOST PEOPLE DON'T
HAVE A HIGH PERCENTAGE OF RET
RETICULOCYTES.
>> YOU CAN ANSWER THAT TWO WAYS.
YOU CAN SEE FROM TO THE FLOW
CYTOMETRY DATA IT'S ABOUT 10% OF
RED BLOOD CELLS TO MAYBE 20% OF
RETICS.
BUT ARE THOSE THE CELLS THAT ARE
SICKLY.
WHEN WE LOOK AT CELLS WITH
MITOCHONDRIA DO THE CELLS THAT
HAVE THE MITOCHONDRIA ARE THOSE
THE FIRST ONE TO SICKLE?
I GUESS YOU CAN SAY NO AND WE
DON'T COMPLETELY KNOW YET.
THANK YOU DR. RIVERS.
>> THANK YOU, SO MUCH.
>> LET'S MOVE ON TO THE NEXT
COMPONENT WHICH IS TRANSFORMING
TECHNOLOGIES TO ASSESS BLOOD
COMPONENTS IN SICKLE CELL THESE
DR. SHEEHAN WILL CHAIR THE
SESSION AND HAS AN EXCELLENT
PANEL OF SPEAKERS.
VIVIEN.
>> THANK YOU SO MUCH.
CAN EVERYONE SEE THE SLIDES
OKAY?
>> YES, WE CAN.
>> AWESOME.
SO I WANT TO GIVE A BRIEF
INTRODUCTION TO THE TALKS.
IT IS AN INTERESTING AND VARIED
PANEL.
WE HAVE TWO ENGINEERS, A
HEMATOLOGIST, A TRANSPLANTER AND
PATHOLOGIST BUT WE ARE ALL
WORKING TOGETHER TO DEVELOP NEW
DEVICES TO STUDY BLOOD FUNCTION
IN SICKLE CELL DISEASE AND OUR
PATIENTS HAVE THE SAME VISCOSITY
AS A PERSON WITH 45%.
THEY ALMOST NEED TO HAVE ANEMIA
TO NOT BE SUPER VISCOUS AND
THEY'RE RIGID AND DEFORMABLE
PARTICULARLY WHEN DEOXYGENATED
AND DAMAGE THE ENDO THELIUM AND
THE QUALITY OF THE RED BLOOD
CELLS IS MORE AB NORMAL
ANDALO-ANTIBODIES CAN BE NEEDED
TO ADDRESS THE PROBLEM.
WE'RE LIVING IN A GOLDEN AGE OF
SICKLE CELL DISEASE WITH THREE
NEW FDA APPROVED THERAPIES AND
IT CREATES A NEW NEED.
NOT ALL NOVEL THERAPIES ARE AS
EASY TO MONITOR WITH HYDROXY
URIA.
WE CAN MAKE SURE OUR PATIENTS
ARE AT THEIR MAXIMUM TOLERATED
DOSE AND IT'S NICE TO GET SEE
WHAT HEMOGLOBIN THEY PRODUCED
BUT CAN TELL IF THEY'RE TAKING
IT IN THE RIGHT DOSE WITH JUST
ROUTINE CONVENTIONAL LABS.
OUR SICKLING AGENTS AND AL
GLUTAMINE DON'T HAVE THE AIM
EASE OF USE AND INTRODUCES THE
QUESTION OF WHICH THERAPY TO ADD
ON TO HYDROXYUREA FOR WHICH
INDIVIDUAL.
WE HAVE SOME EXISTS TOOLS NOT
QUITE IN THE CLINICAL LABORATORY
SPACE AND MANY TRANSLATIONAL
LABS THAT CAN MEASURE RED CELL
QUALITY AND THE MOST NOVEL IS
THE MEASUREMENT OF DEFORMABILITY
AND SICKLING.
SOME VERSIONS OF THIS NOT
INVOLVING OXYGEN GRADIENT ARE IN
USE.
VISCOMETER MEASURE THE WHOLE
BLOOD VISCOSITY AND THE COMMONLY
USED ADVIA BUT FEW REPORT THE
DENSE RED BLOOD CELLS WHICH IS
OF INTEREST TO US LOOKING AT
SICKLE CELL FUNCTION.
AND SOMETHING THAT HEMATOLOGY
ANALYZERS DOES NOT PROVIDE.
ON THE CUSP OF BECOMING
COMMERCIALLY AVAILABLE AND
THERE'S A COMPANY THAT PROVIDES
THIS SERVICE ON THE CLIA
CERTIFIED BASIS AND LOOK AT
PROTEINS THAT LINE THE ENDO
THELIUM.
TO SHOW WHY IT FITS IN YOU CAN
USE THE OXYGEN LEVELS AND CAN
BEGIN TO INVESTIGATE ADHESIONS
AND THERE'S A LOT OF
PATHOPHYSIOLOGY WE'RE NOT ABLE
TO INTERROGATE WITH THESE MORE
COMMONLY USED DEVICES.
SO OXYGEN GRADIENT LOOKS AT THE
DEFORMITY OF THE RED CELLS AND
THEY'RE ADDED TO A VISCOUS
SOLUTION WITHIN THE CHAMBER AND
IT STRETCHES THE RED BLOOD CELL
AND OXYGENATED RED BLOOD CELL
HAS HAVE SOME DEFORMABLE DUE TO
SICKLING OF THE HEMOGLOBIN.
THIS GIVES THREE USEFUL
BIOMARKERS IN CLINICAL TRIALS
AND LIKELY TO BECOME CERTIFIED
FUTURE.
YOU HAVE THE POINT OF AND YOU
HAVE THE OXYGENATED RED BLOOD
CELL AND THEN AND MY LAB HAS
CONTRIBUTED TO SOME CLINICAL
CORRELATIONS OF THE BIOMARKERS
SHOWING IN ADULT AND PEDIATRIC
COHORT THAT INDIVIDUALS WHO HAVE
HAD TWO OR MORE VOC IN THE PAST
TWO YEARS HAVE A HIGHER POINT OF
SICKLING THAN THOSE WHO HAVE NOT
AND SO THIS INDICATES THAT IF
YOU'RE RED CELLS SICKLE YOU'RE
MORE LIKELY TO HAVE A CRISIS IN
THE PAST TWO YEARS.
SO SOME CLINICAL CORRELATIONS
AND EXTENSIVE WORK HAVE BEEN
DONE ON THE DEVICE AND THERE'S
LIMITATIONS TO THE CURRENT
TECHNOLOGIES.
OXYGEN GRADIENT EKTACYTOMETRY
REQUIRES AN EXPERIENCED STAFF
AND GIVES POPULATION LEVEL
MEASUREMENTS AND A SINGLE VALUE
FOR THE WHOLE BLOOD SAMPLE NOT
ALLOWING US TO LOOK AT A SINGLE
CELL FOR SUB POPULATION LEVEL
AND USES OSMOLARITY AND HBS
POLYMERIZATION IS INDIRECTLY
MEASURED AND THERE'S A
POPULATION LEVEL MEASUREMENT.
SO WHAT IS WRONG WITH THE
POPULATION-LEVEL MEASUREMENT?
WELL, IT CERTAINLY IS HELPFUL
AND USEFUL IN LOOKING AT THE RED
CELL IN ADVANCE AND THERE'S
VARIABILITY WITH THE POPULATIONS
AND THE BLOOD YOU MIGHT COLLECT.
MOST HAVE INTEREST RED CELLS
VARYING IN AGE.
IT MAY BECOME IRREVERSIBLY
SICKLING AND MAY HAVE LOST ITS
MEMBRANE AND BECOME MORE OF A
SPHERE MAKING IT DENSER.
AND THEN OF COURSE THERE'S
SPECIAL CONDITIONS BASED ON WHAT
THERAPY THE PATIENTS ARE ON.
GENE-BASED THERAPY YOU'LL GET A
LOT OF HETEROGENEITY BASED ON
THE ASSERTION YOU'RE HAVING IN A
PARTICULAR STEM CELL IT'S
DERIVED FROM AND CRISPR CAS
EDITING AND LOOKING AT DRUG
OCCUPANCY.
IT WOULD BE HELPFUL TO HAVE
SINGLE CELL OR SUB POPULATION
LEVEL MEASUREMENTS TO BETTER
EVALUATE NOVEL THERAPIES.
ONE OF OUR SPEAKERS HAS
DEVELOPED THE OCCLUSION CHIP
WHICH ADDRESSES SOME OF THESE
UNMET NEEDS.
IT DOES MEASURE RED BLOOD CELL
MECHANICALLY IN TERMS OF THE
COST AND AUXILIARY EQUIPMENT
NEEDED IT CAN REPLACE MICROSCOPY
AND THE TRANSPLANTER WILL SHOW
HOW TOGETHER SHE AND I HAVE BEEN
USING RHEOLOGY TO ASSESS
SELF-BASED THERAPIES AND HOW THE
ASSAYS CAN LOOK AT IF THERE'S
CURES IN DISEASE AND ALSO HOW BY
USING THE DIFFERENCE IN
DENSITIES BETWEEN EDITED AND
UNEDITED CELLS ARE TRANSFUSED
HEMOGLOBIN AA CELLS AND MIXED
RECIPIENT SS CELLS WE CAN USE
THE DENSITY TO SEPARATE OUT SUB
POPULATIONS AND STILL BE ABLE TO
USE OUR CURRENT VIROLOGIC
DEVICES WITH THE REFINEMENT OF
ACHIEVING SEPARATION BY RED CELL
FUNCTION IN THIS CASE DENSITY.
AND THEY'LL PRESENT SEVERAL NEW
DEVICES THAT HAVE BEEN DEVELOPED
IN THE LAB THAT ARE THE
PROTOTYPE OR TRANSLATION STAGE.
IT CAN SHOW RED CELL DEFORMITY
ON A SINGLE CELL LEVEL AND
ADHESION AND LOOK AT VISCOSITY
BY DIFFUSION RATHER THAN BY
SHEAR AND LOOKING AT THE EFFECTS
OF RED CELLS ON THE ENDO THELIUM
BUT WHAT DOES THE RED CELL DO
AND WHAT EFFECTS ON PERMEABILITY
AND HOW TO MEASURE THE
DYSFUNCTION AND LOOK AT AN
AUTOMATED ALGORITHM BASED WAY OF
USING DATA FOR DATA ANALYSIS AND
INDIVIDUAL CELL COUNT AND OUR
PATHOLOGIST HAS BEEN DEVELOPING
A WAY TO ENGINEER RED CELLS
BEING AWARE INDIVIDUALS WITH
SICKLE CELL DISEASE IS THE
HIGHEST RATES OF AL FALO -- OF
ALLO-IMMUNIZATION AND THEY'LL
DEVELOP WORK THAT COULD BE A
GAME CHANGER FOR TRANSFUSION
MEDICINE.
ANOTHER COLLEAGUE WILL SHOW HBS
POLYMERIZATION MEETING NEEDS TO
HAVE SINGLE CELL LEVEL TO ASSESS
HOW EFFECTIVE A THERAPY HAS BEEN
ON PREVENTING POLYMERIZATION AND
CAPTURES THE IMPACT OF THE
UNEQUAL DISTRIBUTION WHETHER
THREW INDUCTION OR GENE
STRATEGIES AND SHOW THE DEVICE
SHOWING MEASUREMENTS OF
DEFORMABILITY AND VISCOSITY
MEASUREMENTS UNDER HYPOXIA.
OUR CURRENT COMMERCIALLY
AVAILABLE DEVICES NEED FURTHER
VALIDATION.
THE BEST THING TO BE ABLE TO
SHOW IS THE CHANGING BIOMARKERS
CHANGES CLINICAL OUTCOMES NOT
JUST IN ASSOCIATION BUT WE
ACTUALLY ACHIEVE A CLINICAL
DIFFERENCE IF WE LOWER THE
POINTS, FOR EXAMPLE.
AND CAN THESE BIOMARKERS SERVE
AS CLINICAL TRIAL END POINTS AND
CAN THEY BE USED TO DEFINE
PATIENT CARE AND HAVE A CURE
INTACT?
WE NEED TO FURTHER DEVELOP THE
NOVEL DEVICES WITH SINGLE CELL
AND SUBPOPULATION CAPABILITIES
AND FURTHER EXPLORE RED CELL
ENDOTHELIAL INTERACTIONS AND THE
DEVICES WE'RE GOING TO TALK
ABOUT AND HEAR ABOUT TODAY HAVE
ALREADY THE POTENTIAL TO EXPAND
WHAT ASPECTS OF RED CELL
PATHOPHYSIOLOGY WE CAN EXPLORE.
THE GREEN BOX ARE THE NEW
DEVICES WE'LL BE TALKING ABOUT
TODAY AND THE BLUE ARE THE
EXISTING COMMERCIALLY AVAILABLE
ONES THAT WE HAVE GREATER
FAMILIARITY WITH.
WITH THAT, I WILL HAND THIS OVER
TO TO OUR NEXT SPEAKER DR. UMUT
GURKAN FROM CASE WESTERN
UNIVERSITY.
>> THANK YOU VERY MUCH, VIVIEN.
GOOD AFTERNOON, ALL.
MY NAME IS UMUT GURKAN A
PROFESSOR AT CASE WESTERN
INVESTIGATION AND I'D LIKE TO
TALK ABOUT OCCLUSION CHIP IN NEW
FUNCTIONAL COMPLEMENTARY
EKTACYTOMETRY FOR ASSESSING RED
CELL HEALTH IN SICKLE CELL
DISEASE.
THE COMPROMISED RED BLOOD CELLS
LEAD TO OCCLUSION AND HIGH POM
POX YA.
WE THINK THE OCCLUSION OF
CAPILLARIES CAN BE USED AS A
BIOMARKER TO IDENTIFY PATIENTS
WITH POOR DEFORMABILITY OR HIGH
VISCOSITY AND TO SELECT AND
MONITOR THERAPIES.
WE HAVE DEVELOPED AND TRANSLATED
A NUMBER OF BIO CHIP ASSAY TO
MEASURE RED BLOOD CELL HEALTH
WITH EMERGING THERAPIES.
THESE ASSAYS MEASURE RED CELL IN
FLOW AND MICROCAPILLARY
OCCLUSION IN FLOW.
TODAY I'LL FOCUS ON OCCLUSION
INDEX MEASUREMENT WHICH IS BASED
ON RED BLOOD CELL AND
MICROCAPILLARY FLOW.
MEASURE OCCLUSION INDEX USING A
DEVICE WE CALL OCCLUSION CHIP.
IT'S A FUNCTIONAL MICROCAPILLARY
OCCLUSION ASSAY THAT INCLUDES
NON-UNIFORM NARROW CAPILLARY
OPENINGS AND PASSAGEWAYS.
IT ALLOWS THE ASSESSMENT OF RED
CELLS AS THEY PASS THROUGH
NARROW CAPILLARY OPENINGS.
IT ALLOWS TESTING.
HERE'S THE WORKING PRINCIPLE OF
OCCLUSION CHIP WHERE THE STIFF
RED BLOOD CELLS OCCLUDE THE UP
STREAM CAPILLARIES AND AS MORE
FLOW IN THE CHIP THEY NAVIGATE
PAST THE UPSTREAM BLOCKAGES TO
CAPILLARIES.
AT THE END OF THE TEST WE
PERFORM AN ASSESSMENT AND
QUANTIFICATION OF THE RESULTS.
THIS ASSAY HAS A STANDARDIZED
OCCLUSION OF THE CAPILLARY FROM
WHICH THE OCCLUSION INDEX CAN BE
CALCULATED.
IT REPRESENTS THE PERCENT
OCCLUSION OF THE CAPILLARY AND
IT IS GENERALIZABLE TO ANY
ARTIFICIAL CAPILLARY NETWORK
WHERE THE HIGH OCCLUSION MEANS
THE BLOOD SAMPLE CONTAINS A
LARGE NUMBER OF STIFF RED BLOOD
CELLS RESULT IN THE HIGH
OCCLUSION INDEX.
WE HAVE PERFORMED EXTENSIVE
ANALYTICAL VALIDATION AND HERE'S
A SUMMARY OF THE TEST PERFORMED
WHERE WE USED RIGID MICROBEADS
MIXED WITH HEALTHY RED BLOOD
CELLS TO TEST THE RETENTION
MECHANISM BY THE CAB LIR --
CAPILLARIES MICROSPHERES ARE
RETAINED AT 8 MICROMETER OPENING
CAPILLARIES.
6 MICROMETER BEADS HAVE CAP
LIRLIR
-- CAPILLARIES AND OCCLUSION
DETECTS RED BLOOD CELL
DEFORMABILITY IN A WIDE RANGE OF
PATHOLOGICAL SCENARIOS INCLUDING
ARTIFICIAL MEMBRANE STIFFENING,
HEAVY METAL TOXINS, STORAGE
LESIONS, MALARIA AND SICKLE CELL
DISEASE.
SO THIS ASSAY SHOULD BE
APPLICABLE TO DIFFERENT TYPES OF
DISEASES AND PATHOLOGIES THAT
AFFECT OCCLUSION IN CAPILLARIES.
IT'S SIGNIFICANTLY GREATER IN
INDIVIDUALS WITH SICKLE CELL
DISEASE COMPARED TO HBSS AND
HBSS OCCLUSION INDEX CAN BE
AROUND 3% MEANING 3% OF THE
AVAILABLE CAPILLARY OPENINGS ARE
OCCLUDED BY THE STIFF SICKLE RED
BLOOD CELL AND IT CAN BE USED TO
STRATIFY PATIENTS WHICH WE HAVE
SHOWN ASSOCIATED WITH DISEASE
SEVERITY.
HIGH OCCLUSION INDEX BEYOND THE
CERTAIN THRESHOLD ASSOCIATES
WITH HIGHER HDH AND RETICULOCYTE
COUNTS AND LOWER VALUES IN THE
INDIVIDUALS AND THE MEASUREMENT
OF OCCLUSION INDEX IN HYPOXIA IS
A NEW AND UNIQUE DIMENSION TO
ASSESSING RED BLOOD CELL C
CAPILLARY OCCLUSION IT'S
MEASURED WITH THE USUAL HYPOXIA
LEVELS THAT RESULT IN 8% TO 3%
SPO2 OR SATURATION WITH
HEMOGLOBIN WITH OXYGEN.
IT'S MUCH HIGHER THAN THE
OCCLUSION INDEX IN HDSS AND
ASSOCIATED WITH THE HEMOGLOBIN S
PERCENTAGE IN INDIVIDUALS WITH
SICKLE CELL DISEASE.
WE HAVE SHOWN BOTH EKTACYTOMETRY
DR. VIVIEN SHEEHAN TALKED ABOUT
AND TALKED ABOUT DIFFERENTIATION
OF THE HEALTHY RED BLOOD CELLS
AND OTHERS ARE SHOWN IN THIS
FIGURE.
WE HAVE TESTED THE
REPRODUCIBILITY OF THE CHIP AND
COMPARED IT WITH EKTACYTOMETRY.
THE AVERAGE COEFFICIENT IN
OCCLUSION CHIP WAS LESS THAN 20%
WHEREAS IT WAS AROUND 2% FOR
EKTACYTOMETRY MEASUREMENTS WHICH
WE THINK IS ATTRIBUTABLE TO THE
HIGHER OCCLUSION CHIP WHICH MAY
INDUCE OR RESULT IN HIGHER
VARIATION IN THE MEASUREMENTS OF
THE EXPERIMENTS.
LESS THAN 20% COEFFICIENT OF
VARIATION IS STILL AN ACCEPTABLE
COEFFICIENT VARIATION ACCORDING
TO THE DEVICE REGULATIONS.
AND I WILL TALK ABOUT THE HIGHER
SENSITIVITY OF OCCLUSION CHIP IN
THE NEXT SIDE.
TO TEST THE OCCLUSION CHIP AND
COMPARE IT WITH THE
EKTACYTOMETRY, WE TESTED -- WE
EDIT SMALL FRACTIONS OF STIFF
RED BLOOD CELLS AND MIXED THEM
WITH HEALTHY RED BLOOD CELLS AT
VARYING PERCENTAGES.
SMALL PERCENT RANGING FROM 0% TO
0.1% AND 1%.
THE RANGE OF STIFF RED BLOOD
CELLS MIXED WITH HEALTHY WAS IN
THE RANGE 0 TO 1%.
OCCLUSION CHIP IS SENSITIVE TO
SMALL FRACTIONS OF RED BLOOD
CELLS WITH STIFFNESS AND
SENSITIVELY IS AROUND 0.1%.
EKTACYTOMETRY IN THIS CASE DID
NOT DETECT A DIFFERENCE FOR THE
SMALL FRACTION STIFF RED BLOOD
CELLS MIXED WITH HEALTHY RED
BLOOD CELLS.
NEXT WE COMPARED HYPOXIC
OCCLUSION CHIP FOR SAMPLES THAT
ARE HBAA, HEALTHY NORMAL RED
BLOOD CELLS AND HBSS
POST-TRANSPLANT.
AND OCCLUSION CHIP DETECTED THIS
IN HBSA AND POST-BONE MARROW
TRANSPLANT AND LOWER OXYGEN
GRADIENT EKTACYTOMETRY SHOWED
SIMILAR RESULTS FOR HBA, HBAS
AND HBSS SHOWN HERE ON THE LEFT.
WE THINK IT'S COMPLEMENTARY TO
LOWER CYTOMETRY FOR PROBING
ABNORMALITIES WHEN PERCENTAGE IS
LOW OR AROUND THE UNHEALTHY RED
BLOOD CELL PERCENTAGE IS LOW IN
THE BLOOD SAMPLES.
WE ALSO HAVE SHOWN OCCLUSION CAN
BE USED FOR TESTING OF NEW
PHARMACOLOGIC INTERVENTIONS SUCH
AS THE HEMOGLOBIN OXYGEN
MODIFYING DRUG WHERE IT'S
SIGNIFICANTLY REDUCED IN THE RED
BLOOD CELL AS SHOWN IN THE
FIGURE.
ALL PREVIOUS RESULTS OF
OCCLUSION INDEX MEASUREMENT RELY
ON HIGH RESOLUTION OCCLUSION
CHIP WHICH IS ESSENTIALLY A
MICROFLUIDIC NETWORK OF
CAPILLARY OPENINGS AND LIMITS
THE ACCESSIBILITY OF THE
TECHNOLOGY AND ITS USE IN THE
CLINIC.
FOR THIS REASON WE HAVE RECENTLY
DEVELOPED AN METHOD TO ELIMINATE
THE NEED FOR MICROSCOPY AND
ALLOW A PORTABLE POINT-OF-CARE
UTILIZATION OF THE TECHNOLOGY.
IN THIS METH IT'S MEASURED
BETWEEN WHAT IS DETECTED AND THE
READING FROM THE LEVELS IN THE
CAPILLARY OPENINGS AND THE
MEASUREMENTS CORRELATE WELL WITH
THE OPTICAL OCCLUSION INDEX
MEASUREMENT DETERMINED BY HIGH
RESOLUTION OPTICAL MICROSCOPY
AND HAVE SHOWN THE CORRELATION
CALLS FOR HBA AND HBSS SAMPLES
AND OTHER ABNORMALITY AND THIS
SUGGESTS THE READ OUT IS AS
RELIABLE AS OPTICAL MICRO S
MICROSCOPY-BASED READ OUT.
THE RED CELL INDEX ASSOCIATED
WITH DISEASE SEVERITY FOR
EXAMPLE IN THIS CASE I SHOWED
TWO EXAMPLES WHERE HIGH
ELECTRONIC INDEX ASSOCIATES WITH
HIGH LEVELS OF THE COUNTS AND
LDH IN SICKLE CELL DISEASE.
IN SUMMARY, WE ARE VERY CLOSE TO
ACHIEVING A PORTABLE, ACCESSIBLE
AND SENSITIVE RED BLOOD CELL
ASSESSMENT AT THE POINT-OF-CARE
WHICH WILL BE ENABLED BY THE
MIRCA TECHNOLOGY.
THE FUTURE WORK INCLUDES
CLINICAL VALIDATION OF
ADAPTATION TO CLINICAL STUDIES
AND TRIALS.
A PROTOTYPE ARE CURRENTLY BEING
VALIDATED AT DR. VIVIEN
SHEEHAN'S LAB AT EMORY AND THIS
IS SUPPORTED BY THE MICROSYSTEMS
ENGINEER POINT-OF-CARE
TECHNOLOGIES.
THANK YOU VERY MUCH FOR YOUR
ATTENTION AND PLEASE LET ME KNOW
IF YOU HAVE ANY QUESTIONS.
>> I HAD A QUESTION FOR YOU.
I WAS LOOKING AT THE GLUTEROL
DATA AND LOOKING AT THIS
DIFFERENT WAYS OF MEASURING THIS
MAY BE IMPACTING THIS AND IT'S
NOT JUST VERY WELL CAPTURED BY
THE STRATEGY AND BY THE
DEFORMABILITY STRATEGY.
>> YES.
>> AND NOT SO MUCH A SENSITIVITY
THI
THING.
>> I THINK WE NEED TO FOCUS ON
DIFFERENT ASPECTS AND THE
DEFORMABILITIES MAY BE THE
HIGHLIGHT OF WHAT WE HEARD ABOUT
IN THE WORKSHOP.
>> HOW DOES THIS COMPARE TO
HEMOGLOBIN TYPE AND EXPRESSION.
>> THEY PRODUCE DIFFERENT
RESULTS BASED ON THE HEMOGLOBIN
TYPE AND SB AND WHAT'S BEEN
SHOWN IN SEVERAL PUBLICATIONS.
SO AND LOOKING AT THE OVER ALL
RED BLOOD CELL BUT IT'S NOT
PERFECT HIGHLIGHTING THE
IMPORTANCE OF LOOKING AT RED
CELL FUNCTION AND SO MUCH
ASPECTS IMPACT OUTSIDE OF
HEMOGLOBIN LEVELS.
>> THERE'S ANOTHER QUESTION.
IS THIS GEARED MORE FOR DRUG
EFFICACY?
I THINK SUCH BIO PHYSICAL
ASSESSMENTS CAN LOOK AT THE DRUG
EFFICACY AND POTENCY AND IN
VITRO DRUG DEVELOPMENTS AND
COULD BE ENABLED BY SUCH
TECHNOLOGY AND MULTIPLE
APPLICATION AREAS.
AND THERE'S A QUESTION ABOUT
WHAT IS THE EFFECT OF RED BLOOD
CELL FRAGMENTATION AND IT WILL
BE ANSWERED LIVE.
>> I THINK IT WAS AN ACCIDENT.
I WAS TRYING TO TYPE MY
QUESTION.
>> I'LL TAKE A LOOK.
DO WE HAVE COMMENTS ABOUT RED
BLOOD CELL FRAGMENTATION.
I DO FOR THE LIRCA.
IT WOULDN'T RECOGNIZE IT BECAUSE
IT WON'T HAVE THE RIGHT SIZE OR
BEHAVIOR WITH THE SYSTEM AND FOR
YOUR OCCLUSION CHECK WOULD
PROBABLY PASS THROUGH UNIMPEDED
BECAUSE OF ITS SMALL SIZE.
>> NOW, A QUESTION FROM
DR. GUPTA, IS THE ERYTHROCYTES
SIGNIFICANT SINCE HEMOGLOBIN A
PREVENTS SICKLING EARLY IN LIFE?
I THINK IN THE HYPOXIC
MEASUREMENTS IF THE F LEVELS ARE
HIGH, WHICH WE HAVE SHOWN THE
OCCLUSION INDEX TENDS TO BE
LOWER AND REDUCE SICKLING AND
REDUCE STIFFENING OF THE RED
BLOOD CELLS THAT IS INDUCED BY
FETAL HEMOGLOBIN BUT IS
SOMETHING WE SHOULD LOOK INTO.
IT'S A GOOD COMMENT.
I EXPECT IF SICKLE HEMOGLOBIN IS
PRESENT IN THE SAMPLE WE MAY BE
ABLE TO DETECT A DIFFERENCE IN
THE OCCLUSION INDEX.
>> THE ONE FROM DR. KOETS?
>> HAVE YOU LOOKED AT THIS UNDER
FLOW IT SEEMS FLOW AT THIS LEVEL
IS AN IMPEDENCE PROBLEM RATHER
THAN RESISTANCE.
THAT'S A GOOD QUESTION.
IT'S A GOOD QUESTION.
WE USED IT IN OTHER EXPERIMENTS
BUT NOT IN THIS ONE SO GOOD
COMMENT.
I THINK IT'S WORTH LOOKING AT
THIS INCLUDING HEMOLIYS-LY HEMO
HEMOLY
HEMOLYSIS.
>> THE OSMOSCAN VERSUS THE
COMMERCIAL SCAN.
YOU ALSO SEE THE IMPACT OF PERI
CYTOLOGY.
>> I'M A PATIENT AT UNIVERSE
HOSPITALS AND RETIRED CLINICAL
LAB EMPLOYEE.
SO GLAD TO SEE THE RESULTS THEIR
TECHNOLOGY AND WOULD LIKE TO
THANK THIS INDIVIDUAL.
THANK YOU VERY MUCH.
AND IT WAS POSSIBLE WITH THE
CONTRIBUTION AND INVOLVEMENT OF
THE PATIENTS.
HEMOLIE
AND DOES IT AFFECT THE
MEASUREMENT.
IN ONE SLIDE I SHOW THAT LOW
FETAL HEMOGLOBIN AND HIGH FETAL
HEMOGLOBIN AND MCB RESULTS IN
LOWER INDEX AND HAVE YOU LARGER
CELLS IN THE CASE OF HIGHER H
HEMOGLOBIN LEVELS AND RESULTS IN
A LOWER INDEX WHICH SUGGESTS
THAT THIS TEST IS MEASURING
BASED ON DEFORMABILITY NOT SMALL
DIFFERENCES IN THE VOLUME OR
SIZE.
AND THE DEVICE DEPENDS ON
IMPEDENCE EARLY IN LIFE AND MAY
BE CRITICAL FOR SCREENING.
I UNDERSTAND DR. GUPTA'S
QUESTION BETTER NOW.
I'M NOT SURE IF WE CAN USE THESE
RED BLOOD CELL BIO PHYSICAL
TESTS FOR POINT OF SCREENING FOR
SICKLE CELL DISEASE.
SPECIFICALLY BUT IT'S A GOOD
COMMENT.
WE HAVE NOT TALKED ABOUT THAT SO
WE HAVE OTHER METHODS AND
METHODS FOR POINT-OF-CARE FOR
SICKLE CELL DISEASE BUT THIS IS
AN INTERESTING COMMENT, THANK
YOU.
>> THE CONCERN IS WITH HIGH
FETAL HEMOGLOBIN AT FURTHER THE
RED BLOOD CELL WOULD APPEAR
ESSENTIALLY NORMAL.
>> YES.
AND IT'S BEEN LOOK AT IN MALARIA
TO LOOK AT THE IMPACT OF RED
BLOOD CELL DEFORMABILITY.
IT WOULD BE GREAT TO LOOK AT
THIS.
I THINK IT'S A GOOD COMMENT.
>> LET'S TAKE ONE MORE QUESTION.
I'M GLAD IT'S GETTING SO MUCH
INTEREST.
>> DR. COATES SAID IT WOULD BE
INTERESTING TO LOOK AT THE SETS
WITH MISSING ALPHA AND WONDERING
IF YOU CAN DETECT A DIFFERENCE
IN DEFORMABILITY.
WE HAVE TALKED ABOUT THIS QUITE
A BIT LOOKING AT THE EFFECT OF
ALPHA TAU.
WE'RE INTERESTED AND DR. COATES
IF YOU'RE INTERESTED IN LOOKING
AT THIS TOGETHER WE'D BE HAPPY
TO DO THAT.
THAT'S A GOOD COMMENT.
>> IT HIGHLIGHTS THE CHALLENGES.
THE LIRKA CAN SOMETIMES DETECT
WITH OXYGEN GRADIENT A
DIFFERENCE BETWEEN A NORMAL AND
TRAIT BUT NOT RELIABLY AND NOT
ON EVERY DEVICE.
SOMETHING I'VE ASKED UMUT TO
HELP WITH IS TO DEVELOP THE
DEVICE THAT WOULD RELIABLY BE
ABLE TO INTERROGATE TRAIT NOT
JUST WITH KNOWN MODIFIERS BUT
WITH GREATER VARIABILITY CAUSED
BY MEMBRANOPATHY DIFFERENCES AND
THINGS THAT MAY EXPLAINS WHAT
DRIVES TRAIT DIFFERENCES ON AN
EPIDEMIOLOGY LEVEL.
>> VERY GOOD QUESTION AND
COMMENT.
>> OUR NEXT SPEAKER, THEN --
>> WOULD YOU LIKE ME TO
INTRODUCE.
>> YES, LET'S ALL GET IN THAT
HABIT.
>> OUR NEXT SBAEPEAKER IS TAMI N
FROM CHILDREN'S HOSPITAL BAYLOR
COLLEGE OF MEDICINE.
>> CAN YOU SEE THAT.
I'M TAMI JOHN FROM TEXAS
CHILDREN'S HOSPITAL, BAYLOR
MEDICINE AND THANK YOU FOR THE
RBC FUNCTION AFTER THERAPIES
WITH CURATIVE INTENT.
I'M A CLINICIAN SO THIS IS A
SHIFT IN CONVERSATION LOOKING AT
CLINICAL ASPECT AND SPECIFICALLY
THE WORK.
I HAVE NO PERSONAL FINANCIAL
DISCLOSURES BUT HAVE INTEREST IN
THERAPIES RELATED TO DEVELOPED.
-- SICKLE CELL DISEASE AND I
HAVE CURE IN QUOTATIONS.
IN THE CONTEXT OF CORRECTIVE
CELLULAR THERAPIES.
I'LL DISCUSS THE CONCEPT OF RBC
FUNCTION AND FUNCTIONAL ANALYSIS
USING EKTACYTOMETRY AND SHIFT
GEARS TO DISCUSS DONOR CELL
ENGRAFTMENT AFTER TRANSPLANT FOR
SICKLE CELL DISEASE AND CONCLUDE
WITH FINAL THOUGHTS AND
RELEVANCE AND FUTURE
CONSIDERATIONS.
SO AS WAS PRESENTED YESTERDAY,
CORRECTIVE THERAPIES WITH
CURATIVE INTENT FOR SICKLE CELL
DISEASE ARE CURRENTLY DIVIDED
INTO THE ALLO GENIC STEM
TRANSPLANT AND MANY PEOPLE
EXCITED ABOUT THIS RESEARCH AND
THE DEVELOPMENT OF REDUCED
TOXICITY.
THE SECOND IS AUTOLOGOUS
GENE-MODIFIED THERAPIES WITH AN
INSERTION AND SILENCE AND
CORRECTION AMONG OTHERS.
SO IN GENERAL, THERAPIES
TARGETED TO CURE SICKLE CELL
DISEASE AT LEAST FROM MY
PERSPECTIVE SHOULD BE CORRECTIVE
SUCH THAT RESOLUTION OF THE
CLINICAL PHENOTYPE IS SEEN FIRST
AND FOREMOST.
THIS IS ACHIEVED BIO LOGICALLY
THROUGH EXPRESSION OF A
NON-SICKLING HEMOGLOBIN THAT
MIMICS OR ELIMINATES ERYTHROCYTE
SICKLING AND THE REMAINDER OF
THIS TALK IS IN REGARDS TO RED
BLOOD CELL DEFORMITY AS ASSESSED
BY ANALYZER WORK AS DR. SHEEHAN
HAD PRESENTED.
THE ADDITIONAL APPLICATION OF AN
OXYGEN GRADIENT HAS ALLOWED FOR
ASSESSMENT OF DEFORMABILITY IN
SHEER STRESS DURING OXYGEN
DEPLETION.
AS DR. SHEEHAN HAS SHOWN, THIS
GRAPHICAL REPRESENTATION ON THE
RIGHT IS WHAT'S PRODUCED AFTER
ANALYSIS OF THE WORK UP.
DATA POINTS TO INCLUDE THE POINT
OF SICKLING AT THE OXYGEN
CONCENTRATION WHERE THE
DEFORMABILITY DECLINES AND THE
CELLS BEGIN TO SICKLE.
THE INDEX IS A NUMERICAL VALUE
OF DEFORMITY WITH THE I.E. MAX
DESCRIBING DEFORMABILITY UNDER
OXYGEN CONDITIONS AND THE THEN
THE DELTA BETWEEN THE TWO.
THE PICTORIAL ON THE RIGHT SHOWS
RED CELL DEFORMITY PER CELL TYPE
AND I'LL NOTE THE TOP BLUE RYAN
REPRESENTS HEMOGLOBIN AA RED
CELLS UNAFFECTED BY HYPOXIA.
THE PURPLE CURVE IS REFLECTIVE
OF THE RED BLOOD CELLS OR SICKLE
CELL TRAIT AND LOOKING AT
CONCENTRATION WITHOUT THE
ELONGATION INDEX OR SIGNIFICANT
SIGNALLING.
THE RED LINE AT THE BOTTOM
REPRESENTS THE RED BLOOD CELLS
WHERE DEFORMABILITY DECLINES
PRECIPITOUSLY WITH HYPOXIA
CREATING THE INDEX CURVE.
RED BLOOD CELL DEFORMITY WITH A
VARIETY OF EXPOSURES HAS BEEN
DESCRIBED AND THE LOWEST SOLID
BLACK LINE YOU SEE HERE
REPRESENTS UNTREATED RED BLOOD
CELLS IN HEMOGLOBIN SS DISEASE.
THEED TO LINE REPRESENTS THE
TRANSFUSED SICKLE CELL DISEASE
AND THE MIDDLE LINES REPRESENT
SICKLE CELL DISEASE WITH VARIOUS
FACTORS SUCH AS THE HYDROXYUREA
EXPOSURE WITH A YOUNG PATIENT
UNDER 5 YEARS OR SS DISEASE AND
THE HIGH POINT OF SICKLING BY
THE RIGHT LINE WHEN LOOKING AT
UNTREATED HEMOGLOBIN SS COMPARED
TO ALL THESE OTHER SICKLE CELL
DISEASE WITH OTHER EXPOSURES.
FURTHER, NOTE THE DIFFERENCES IN
THE ELONGATION INDEXES WHEN
COMPARED TO UNTREATED HEMOGLOBIN
SS.
GENERALLY DEOXYGENATION IS
REPRESENTED BY THE CHANGES IN
THE ELONGATION INDEX
PARTICULARLY IN THE YOUNGER
PATIENTS AN THOSE WHO HAVE BEEN
TRANSFUSED COMPARED TO
HEMOGLOBIN SS WITHOUT THERAPIES.
THIS DEPICT THE DEFORMITY
WITHOUT GRADIENT.
IN A PATIENT WITH SICKLE CELL
DISEASE RECENTLY HAVING RECEIVED
RED CELL EXCHANGE THEY WERE
ANALYZED AND NOTE THE POINT OF
SICKLING UP HERE IN THE WHOLE
BLOOD IS RELATIVELY LOW COMPARED
TO THE NON-TREATED SICKLE CELL
I'LL SHOW IN FUTURE SLIDES AT
ABOUT 14.5 MILLIGRAMS MERCURY.
AS EXPECTED GIVEN THE THERAPY
AND AFTER INTENSITY SORTING, THE
POPULATION OF CELLS IS IDENTIFY
WITH A HIGH POINT OF SICKLING
AND FORMABILITY REFLECTIVE AND
SHOWN ON THE CURVE.
YOU CAN SEPARATE OUT CELLS BY
DENSITY AND LOOK AT THEIR
FUNCTION INDIVIDUALLY.
TO SHIFT GEARS SLIGHTLY BACK TO
THE CURATIVE THERAPIES AND THE
CLINICAL REALM AS WE HEARD
YESTERDAY WE HEARD THE SUCCESSES
OF THE THERAPY WE CONSIDER
CURATIVE AND THERE WAS A REPORT
THE LARGEST META-ANALYSIS OF
SICKLE CELL DISEASE AFTER BONE
MARROW TRANSPLANT FROM A DONOR
FROM MYBLATED BLOOD AND TO
EXPAND DONOR POSSIBILITIES BEING
EXPLORED WITH HIGH POPULARITY.
THOUGH WITH THE EXPLORATION
WE'RE RECOGNIZING THERE'S AN
INCREASED RISK FOR INCREASED
ENGRAFTMENT UP TO 40% TO 50% OF
PATIENTS INCLUDING MYOBLATIVE
CONDITIONING UP TO 30%.
I'VE GIVEN THE RISK OF HIGH
RATES WITH THE CONDITIONING
REGIMENTS UNDERSTANDING THE
IMPACT OF MIXED DONOR CHIMERISM
IS AFFECTED ABOUT THE DEGREE OF
CORRECTION AND NIH PUBLISHED A
MODEL HERE THAT CAN PREDICT
HEMOGLOBIN PERCENT WITH MYELOID
ENGRAFTMENT AND AS THE DONOR
CHIMERISM DECREASES HEMOGLOBIN
AFFECTS ABOUT 50% IN RECIPIENT
FROM AN A.S. DONOR WHICH IS
CLEARLY CONCERNING SEEING
INCREASES BEYOND WHAT THE DONOR
SHOULD REPRESENT.
SO THEY HYPOTHESIZED OR
THEORIZED THE DONOR CHIMERISM
CAN BE VERY LOW BECAUSE NORMAL
PRECURSORS OUTLIVE THE
ERYTHROPOIESIS AND CAN STILL
MAINTAIN CORRECTION OF THE
PHENOTYPE.
AND WE HAVE MONITORED PATIENTS
WHO SERVICED THE TRANSPLANT AND
WE SEE A RATE OF MIXED CHIMERISM
SIMILAR TO THE REPORT AROUND 40%
TO 50%.
IN TWO CASES, HOWEVER, WE SAW
DONOR CHIMERISM THAT WAS QUITE
LOW.
THE MAJORITY HAD THEM IN THE 90%
DONOR MYELOID COMPARTMENT AS
COMPARED TO JUST THE TWO THAT
HAVE SIGNIFICANT LOWER CHIMERISM
BELOW 50%.
IN BOTH CASES I HAVE THEM
DESPITE ON THE RIGHT ONE HAD
DONOR MYELOID CHIMERISM AND BOTH
WERE NEARING 10 YEARS OUT OF
TRANSPLANT AND NOTABLY THE
PATIENT WITH 15% HAD HEMOGLOBIN
S OF 43%.
AND A DONOR WHO HAD GENOTYPE AA
AND SHOULD HAVE EVIDENCE OF
HEMOGLOBIN SS HADN'T HAD
SIGNIFICANT OR ACUTE SICKLE CELL
MANIFESTATIONS THOUGH ON
LABORATORY FINDINGS HAS EVIDENCE
OF HEMOLYSIS AND DIDN'T REQUIRE
SIGNIFICANT INTERVENTIONS.
THE SECOND PATIENT HAD A
HEMOGLOBIN SS OF 4% AND DIDN'T
HAVE ACUTE COMPLICATIONS OF
SICKLE CELL DISEASE.
AND WE LOOKED IN CONJUNCTION OF
DR. SHEEHAN WITH TRANSPLANTS
WITH CHIMERISM.
IN THE LEFT TWO IN THE BOTTOM
RIGHT GRAPH AND LOOK AT
INTERMEDIATE CHIMERISM OF 50% TO
90% HOWEVER, RED CELL FUNCTION
THAT REFLECTS THAT OF OUR AA AND
AS DONOR AND YOU SEE THE FLOOD
LINES OR FLATLY CURVE LINES
CONSISTENT WITH THE RED BLOOD
CELLS.
ON THE TOP RIGHT WE HAVE LOOKED
AT CORRECTION WITH RED BLOOD
CELL DEFORMITY CONSISTENT WITH
THE DONOR AND WE CAN LOOK AT
SUSTAINED PROTECTION FROM
CLINICAL EVENTS BUT AT
POPULATION-LEVEL ASSESSMENT WE
SEE THAT A BIOLOGICAL CURE HAS
NOT BEEN ACHIEVED WITH RED BLOOD
CELL S THAT AFFECT HYDROXYUREA.
ALSO AS PRESENTED YESTERDAY A
FEW TIMES AND PUBLISHED, WE HAVE
SEEN CLEARER CLINICAL RELEVANCE
WITH COMPLETION OF THE ACUTE
OCCLUSIVE CRISIS AND THOSE
PROFOUND IN THE PRE AND POST
EVENTS AND BUY LODGE EXPRESSION
IN THE GROUP C COHORT IS
REPORTED AT 40% TO 50% WITH
EXPRESSION OF THAT IN 80% TO 90%
OF RED BLOOD CELLS.
THERE'S A POPULATION OF CELLS
THAT ARE BETA S ONLY AND 10% TO
12% OF THE CELLS.
THE SHEEHAN LAB PERFORM ED
CYTOMETRIC EVALUATION AND THE
CURVE IS SHOWN HERE.
IN THIS PARTICULAR INDIVIDUAL
THE HEMOGLOBIN WAS NORMAL AT
12.2.
THE PATIENT HAS NO SIGNIFICANT
SIGNS OF HEMOLYSIS AND THE BLOOD
SICKLES AND THEY LOOK AT 17.5
AND THE CELLS ARE POORLY
DEFORMABLE ON POPULATION
ANALYSIS.
AND SHOWS FUNCTION IN WHAT WE
CALL DISEASE RANGE RESEMBLING
THAT OF A PERSON TRANSFUSED WITH
SICKLE CELL DISEASE.
AND CORRECTION OF THE SICKLING
PHENOTYPE INCLUDING ANEMIA
THOUGH A POPULATION OF SICKLE
CELLS PERSIST THOUGH MAY BE
HEAVILY DILUTED.
LESSONS LEARNED FROM THIS CASE
INCLUDING THE FOLLOWING THERAPY
RESULTS IN BENEFIT FROM
SUSTAINED COLLISION OF SICKLE
CELL DISEASE HOWEVER A
POPULATION OF SICKLE CELLS
CO-EXIST ON POPULATION LEVEL
ANALYSIS EXHIBIT DISEASE LEVEL
FUNCTION.
AND I SUSPECT IF WE LOOK AT THE
GRADIENT ANALYSIS THEY LOOK LIKE
SICKLE CELL DISEASE THOUGH YOU
MAY FIND INTERESTING -- YOU SEE
INTERESTING FINDINGS WITH
PARTIAL CORRECTIONS AND
CORRELATION OF POPULATION
ANALYSIS AND THEN REALLY LOOKING
AT DENSITY GRADIENT ANALYSIS
AFTER THERAPIES IS NEEDED TO
HELP US ELUCIDATE SOME OF THE
RELEVANCE OF THESE FINDINGS.
AND FINALLY AMONG PATIENTS WHO
HAVE RECEIVED OTHER GENE
MODIFICATION THERAPIES AND GENE
EDITING APPROACHES I THINK IT
WILL BE INTERESTING TO ASSESS
WHAT A POPULATION LEVEL AND
DENSITY GRADIENT SORTING WHAT
THE RED CELL FUNCTION LOOKS LIKE
IN COMPARISON.
TO CONCLUDE, RED BLOOD CELL
ANALYSIS WITH OXYGEN GRADIENT
DESCRIBES DISEASE OF DISEASE
CORRECTION WITH POTENTIAL
APPLICABILITY IN PARTIALLY
CORRECTIVE THERAPIES.
CERTAINLY LARGE SCALE ANALYSES
ARE NEEDED TO UNDERSTAND THE
RELEVANCE OF POPULATION-LEVEL
DISEASE RANGE RED BLOOD CELL
FUNCTION PARTICULARLY BECAUSE
CLINICAL BENEFIT FROM THESE
THERAPIES SEEMS TO EXCEED THAT
EXPECTED BASED ON THE FUNCTIONAL
ANALYSIS WE'VE SHOWN TODAY.
QUESTIONS REMAIN REGARDING THE
SIGNIFICANCE OF ONGOING SICKLING
IN A SMALL POPULATION OF CELLS.
WHAT'S THAT MEAN IN AS FAR AS
ORGAN TOXICITY AND STRESS AND
LOOKING AT LIMITATIONS IN
POPULATION ANALYSIS AND MAY HELP
IDENTIFY CLINICAL THRESHOLDS TO
LOOK AT ACUTE AND CHRONIC SICKLE
CELL DISEASE.
MORE INFORMATION IS NEEDED
REGARDING CORRELATION AND
PREDICTABILITY OF CLINICAL
OUTCOMES USING THE BIOMARKERS
AND MAY BE A TOOL IN CONJUNCTION
WITH THE OTHER BIOMARKERS
PRESENTED TODAY THAT CAN HELP
DESCRIBE OUTCOMES FROM THERAPIES
AND CORRELATE WITH CLINICAL
EXPECTATIONS.
WITH THAT I WOULD LIKE TO THANK
ALL THE PATIENTS IN THE FAMILIES
THAT ALLOW AND HAVE SPENT SO
MUCH TIME WITH US AND ALLOW US
AND ENTRUST US WITH THEIR
MEDICAL CARE TO THE SHEEHAN LAB
AT EMORY AND VIVIEN SHEEHAN WHO
HAS RUN ALL THE SAMPLES WE RUN
PORCH TO OUR TEXAS CHILDREN'S
PROCUREMENT TEAM WHO PROCESS
BLOOD SAMPLES AND TO OUR BONE
MARROW TRANSPLANTS AT CHILDREN'S
TEXAS HOSPITAL WHERE WE SEE
NUMEROUS PATIENTS DAILY AND
THANK YOU FOR TO THE NIH FOR
ALLOWING ME TO PRESENT TODAY.
WITH THAT I CAN ANSWER SOME
QUESTIONS.
>> THAT'S A TYPICAL TRANSFUSED
TO 30% HEMOGLOBIN SICKLING AND
WE TOOK A PATIENT ON TRANSFUSION
AND SUPERIOR IMPOSED THE CURVE
WITH MIXED CHIMERISM WHICH
SHOULD HAVE BEEN ENOUGH TO BE
CURATIVE AND APPEARS TO BE MORE
SIMILAR TO A CHRONICALLY
TRANSFUSED TRANSPLANT PATIENT
WHICH IS NOT CURATIVE.
AND THERE'LL BE AN OPPORTUNITY
TO ASK QUESTIONS AT THE END AS
WELL.
>> WITH THAT I'LL INTRODUCE
DR. CHRISTINA CARUSO FROM EMORY
UNIVERSITY.
BEFORE I DO THAT I WANT TO SAY
CONGRATULATIONS.
WE HAVE SOMEONE WHO JUST
CELEBRATED SIX YEARS AND WE'RE
VERY GRATEFUL TO HERE ALL THE
NEW OUTCOMES AND CONGRATULATIONS
TO YOU.
AND WITH THAT TO DR. CHRIS DENA
CARUSO FROM EMORY.
>> HI, EVERYBODY.
HOPEFULLY YOU'RE ABLE TO HEAR ME
WHILE I PULL UP MY SLIDES.
ALL RIGHT.
ARE YOU ABLE TO SEE MY SLIDES?
OKAY.
WELL, GOOD AFTERNOON.
MY NAME IS CHRISTINA CARUSO.
I'M AN INSTRUCTOR AT EMORY AND
WILL BE DISCUSSING SOME OF OUR
WORK IN THE LAB DURING
LEVERAGING MICROFLUIDICS ASSAYS
AS FUNCTIONAL ANALYSIS TOOLS IN
SICKLE CELL DISEASE.
ARE YOU GUYS ABLE TO SEE MINE?
IT SAYS IT'S PAUSED ON MY
SCREEN.
>> I'M NOT SEEING YOUR SLIDES.
>> HERE'S A BRIEF OUTLINE OF
WHAT I PLAN TO TALK TO YOU ALL
ABOUT DURING THIS PRESENTATION.
SO I'LL GIVE SOME BACKGROUND ON
MICROFLUIDIC IS AS AND WHY
THEY'RE GREAT TOOLS FOR STUDYING
SICKLE CELL DISEASE AS WELL AS
OTHER HEMATOLOGIC DISORDERS AND
LOOK AT THE PATHOPHYSIOLOGY THAT
CAN BE ASSESSED IN ADDITION TO
HOW SOME OF THE APPLICATIONS CAN
BE COUPLED WITH HEMATOLOGY
SOFTWARE FOR ROBUST OUTPUT.
THIS PRESENTATION WILL SERVE AS
A LITTLE BIT OF A MICROFLUIDIC
BUFFET WHERE I GIVE A SMALL
TASTE OF THE EXPERIMENTS
PERFORMED WITH OUR ASSAYS.
I KNOW I DON'T NEED TO INTRODUCE
THE RED CELL TO THIS AUDIENCE
BUT I WILL MENTION THERE'S MANY
CLINICAL PROPERTIES THAT ALLOW
FOR IT TO DO ITS JOB WELL AND IN
PARTICULAR THE CELL MEMBRANE
PROVIDES PROPERTIES ESSENTIAL
FOR PHYSIOLOGIC CELL FUNCTION
AND TRA FIRSTING THE CIRCULATORY
SYSTEM AND IN PARTICULAR THE
CAPILLARY NETWORK.
THEY'RE ALTERED IN SICKLE CELL
DISEASE AND PREVIOUSLY DISCUSSED
AND THE DECREASED DEFORMABILITY
AND RED CELLS AND OTHER
DISORDERS ARE OF PARTICULAR
INTEREST TO ME AND OTHERS IN OUR
GROUP.
WHY IS RED CELL DEFORMABILITY
IMPORTANT?
ALTERATIONS IN THE PHYSICAL
PROPERTIES SICH AS AND SUCH
ALTERATIONS CAN IMPACT
ENDOTHELIAL FUNCTION AND IMPACT
MANY FUNCTIONS AND THE FUNCTION
CAN PLAY A ROLE IN VASCULOPATHY
AND SOME TECHNIQUES LOOK AT THE
ENTIRE RED CELL POPULATION AND
THOSE THAT ASSESS DEFORMABILITY
AND YOU LOOKED AT ONE TOOL IN
EKTACYTOMETRY AND AN EXAMPLE IS
ATOMIC FORCE MICROSCOPY.
IT CAN GATHER INFORMATION BY
FEELING OR TOUCHING A SURFACE
WITH THE MECHANICAL PROBE AND AN
ABILITY IS TO MEASURE THE FORCES
BETWEEN THE PROBE AND THE SAMPLE
AS A FUNCTION OF THEIR MUTUAL
SEPARATION.
AND THIS CAN BE APPLIED TO
MEASURE THE MECHANICAL
PROPERTIES SUCH AS THE MEASURE
OF STIFFNESS.
AFM IS FANTASTIC AT MEASURING
VARIATIONS AT THE SINGLE CELL
LEVEL BUT TIME INTENSIVE AND
THROUGHPUT SO NOT ENTIRELY
REPRESENTATIVE OF A POPULATION.
CAN THESE MODELS DESIGN TO MIMIC
THE VASCULATURE LOOK AT
PROPERTIES OF RED CELLS AND
ALTERED FLOW AND ENDOTHELIAL
FUNCTION AND THE ANSWER IS A
RESOUNDING YES AND YOU SEE THE
DEVICE ON THE TOP LEFT AND IF
YOU TAKE THAT OPPOSED TO THE
SIGNIFICANTLY DISTURBED OR
ALTERED FLOW SEEN ON THE BOTTOM
INCLUDING CHANNELS WITH FULL
OCCLUSION WITH A PATIENT WITH
SICKLE CELL DISEASE.
SO ENDOTHELIALIZED MODELS CAN
SERVE AS A MODEL OF THE
VASCULATURE AND THESE ARE THE
TWO I'VE USED IN THE LAB WITH
THE TOP SHOWING A STRAIGHT
CHANNEL DEVICE WHERE EACH HAS A
DIAMETER OF 100 MICRONS AND THE
BOTTOM SHOWING A 32-CHANNEL
BRANCHING DEVICE WHERE THE
SMALLEST BRANCHES HAVE A
DIAMETER OF 30 MICRONS.
IN THE LAB WE UTILIZE DIFFERENT
SIZES OR GEOMETRIES OR
CONFIGURATIONS.
ON THE RIGHT YOU CAN SEE A
CARTOON OF HOW WE ENDOTHELIALIZE
THE DEVICES.
WE START WITH A SILICONE-BASED
DEVICE BONDED TO A COVER SLIP
AND INTRODUCE ENDOTHELIAL CELLS
IN THE DEVICES AND EXPOSE THEM
TO PHYSIO LOGIC FLOW LEADING TO
A HOMOGENEOUS LAYER LINING THE
MICROFLUIDIC DEVICE.
AS ENDOTHELIAL CELLS RESPOND
POSITIVELY TO FLOW CONDITIONS WE
CAN USE THAT IN CREATING OUR
DEVICES.
ON THE RIGHT SIDE WHEN NO FLOW
IS APPLIED, CELLS LOOK
DISORGANIZED AND HETEROGENEOUS
BUT THEY WHEN HAPPY THEY CAN
ARRANGE IN A NICE LAYER ON THE
LEFT.
WHAT ARE SOME WAYS THE ASSAYS
CAN BE APPLIED TO THE STUDY OF
SICKLE CELL DISEASE?
WELL, WE SINGLE CELL
MEASUREMENTS AND ASSAYS AND DO
BULK CELL SUSPENSION
MEASUREMENTS SUCH AS OCCLUSION
ASSAYS AND LOOK BEYOND THE BLOOD
AND MEASURE ENDOTHELIAL HEALTH
AND DYSFUNCTION.
WITH ALL THESE ASSAYS AND
APPLICATIONS IS MANUAL DATA
ANALYSIS OUR ONLY OPTION?
I'M THE FIRST TO ADMIT I'VE DONE
MY FIRST SHARE OF MANUAL
ANALYSIS WITHIN MICROFLUIDIC
DEVICES FOR SOME OF MY
EXPERIMENTS AND PARTICULARLY IN
REGARD TO ASSESSING ENDOTHELIAL
DYSFUNCTION.
HOWEVER, MANUAL ANALYSIS CAN BE
ERROR PRONE.
THANKS TO A WONDERFUL GRADUATE
STUDENT IN OUR LAB WE NOW HAVE A
PRECISE AND COMPREHENSIVE
SOFTWARE ANALYSIS TOOL CALLED
I-PLOTS WHICH HAS BEEN MADE OPEN
SOURCE THAT CAN BE LEVERAGED IN
CONJUNCTION WITH MANY OF OUR
MICROFLUIDIC ASSAYS AS WELL AS
FOR OTHER APPLICATIONS.
SO JUST A LITTLE BRIEF
INTRODUCTION TO THAT SOFTWARE
BEFORE I TELL YOU ABOUT SOME OF
OUR ASSAYS AND ITS APPLICATIONS.
THE SOFTWARE ENABLES THE
QUANTIFICATION OF MICROSCOPY
DATA FROM A WIDE RANGE OF
HEMATOLOGY ASSAYS.
IT'S VERSATILE METHODS ADOPT TO
VIDEO MICROSCOPY OF CELLS AND
CELL SUSPENSIONS FROM TAKEN FROM
A VARIETY OF EXPERIMENTAL
SYSTEMS AND DEVICES INCLUDING
WITHIN BULK STATIC AND
FLOW-BASED DEVICES AND HERE'S
EXAMPLES ON THE LEFT OF THE
FIGURE.
AND I-PLOTS ANALYZES EXTERNALLY
COLLECTED DATA MAKING IT
SUITABLE FOR DATA PREVIOUSLY
COLLECTED OR NEW AND YOU CAN
SELECT VARIATIONS AND
ACCUMULATION APPLICATION THAT'S
PROMOTE FOR THE EXPERIMENT THEY
PERFORMED AND EACH APPLICATION
FACILITATES INTERACTIVE ANALYSIS
OF A SPECIFIC EXPERIMENTAL WORK
FLOW.
AND THEN FROM THE PROVIDED
MICROSCOPY IMAGING DATA DATA
CORRESPONDING TO EACH INDEX ON
AN INPUT FILE IS AUTOMATICALLY
GENERATE AND CLUSTERING
ALGORITHM AND IT CAN BE USED
WITH THE CREATION OF A SINGLE
CELL DEFORMABILITY INDEX DEFINED
AS THE VELOCITY AND THE CELLS
PASSING THROUGH THE CAPILLARY
CHANNELS.
YOU CAN SEE A MICROSCOPIC VIEW
ON THE TOP OF OUR SINGLE-CELL
MICROFLUIDIC DEVICE DESIGNED TO
MIMIC THE CAPILLARY BED WITH THE
MICROSCOPY ON THE BOTTOM OF THE
REGION OF INTEREST OF 20X
MAGNIFY FICTION AND YOU CAN SEE
WHAT TRAVEL THE CHANNELS CIRCLED
IN GREEN HERE AND THEN IN THE
MIDDLE YOU CAN SEE THE SELECT
IMAGES FROM THE SOFTWARE OUTPUT
SHOWING A REPRESENTATIVE HEALTHY
CONTROL RED CELL IN THIS CASE
BEING TRACKED ACROSS FRAMES AND
THE SOFTWARE REPORTS CELL SIZE
PRIOR TO THE CELL'S ENTRY INTO
THE SMALLEST CHANNELS BEFORE THE
SHAPE HAS BEEN CHANGED OR
ALTERED IN ANY WAY.
ON THE RIGHT YOU CAN SEE A VIDEO
WHICH HAS SLOWED DOWN TO MAKE IT
EASIER TO SEE.
I HOPE YOU CAN APPRECIATE SOME
OF THE RED CELLS SQUEEZING INTO
AND TRAVERSING THE
MICROCHANNELS.
AND THEN HERE YOU CAN SEE SOME
REAL-TIME ANALYSIS WITHIN
I-PLOTS OF SINGLE CELL DEFORMITY
MEASUREMENTS OF HEALTHY
CONTROLLED RED CELLS IN BLUE AND
SICKLE CELLS IN RED AND A REGION
WAS SELECTED THE ENTIRE LENGTH
OF THE CAPILLARY CHANNEL AND THE
MEASUREMENT OF DEFORMABILITY ARE
SHOWN ON THE RIGHT AS ACQUIRED
AND EVEN WITH THE SMALL SNAPSHOT
OF CELLS YOU CAN SEE THE SICKLE
CELL RED CELLS HAVE A LESS
DEFORMABLE THAN HEALTHY CONTROL
CELLS.
AND HERE ON THE LEFT IS SDI DATA
FOR RED CELLS FROM ONE HEALTHY
DONOR IN BLUE AND ONE HEMOGLOBIN
PATIENT IN RED AND THIS SHOWS
FROM FIVE MICROLITERS OF BLOOD
IN THE CASE WE ANALYZED A TOTAL
OF 1500 HEALTHY CELLS AND 250000
SICKLE RED CELLS AND THEY WERE
FOUND LESS DEFORMABLE THAN
HEALTHY CONTROLS AND A
POPULATION OF SICKLE CELL RANGE
AND IN ADDITIONALLY THE SOFTWARE
CLUSTERING ALGORITHMS COMBINED
DISEASED AND HEALTHY CELLS INTO
A MATHEMATICALLY DEFINED
CLUSTERS SHOWN ON THE RIGHT SIDE
AND DIFFERENCES BETWEEN EVENT
FREQUENCY WITHIN CLUSTER SHOW
MORE SICKLE CELL EXIST IN THE
SMALLER LOW SDI CLUSTER
DEMONSTRATED IN YELLOW WHICH IS
IN SUPPORT OF THE FINDINGS FROM
THE OVER ALL PATIENT POPULATION
WHICH IS SEEN ON THE LEFT.
AND IN ADDITION YOU CAN ALSO SEE
WITHIN THE CLUSTER INFORMATION
THAT SIZE OF RED CELLS IS
MEASURED IN ADDITION TO THE
DEFORMABILITY DATA AND ALLOWS
FOR THE CREATION OF THE PLOT OF
SDI VERSUS CELL SIZE.
YOU CAN EASILY APPRECIATE THE
INCREASED HETEROGENEITY OF RED
CELLS WITHIN THE DATA AND IN
ADDITION TO ISOLATED RED CELLS
ARE COUPLED WITH OUR
MICROFLUIDIC CAN SUPPORT
ANALYSIS OF VARIOUS CELL LINES
AS WELL AS FLUORESCENTLY TAGGED
CELLS SUCH AS RETICULOCYTES AND
NEXT YOU'LL DISCUSS OUR
OCCLUSION STUDIES IN OUR
MICROFLUIDICS.
AND SOME CHANNELS ARE COMPLETELY
OCCLUDED WHILE OTHERS HAVE
PARTIAL OCCLUSION AND THERE'S
CLEAR ALTERATIONS IN FLOW
DEMONSTRATED AS WELL.
SO THERE'S A LOT GOING ON THE
SLIDE AND I'LL HIGHLIGHT WHAT
YOU'RE SEEING.
AND THIS IS ACTUALLY SHOWING
SOME ACCUMULATION AND OCCLUSION
DATA WITH ITS ANALYSIS WITHIN
THE I-PLOTS.
OCCLUSION AND ACCUMULATION CAN
BE USED WITH COMMERCIALLY
AVAILABLE AND SPECIALLY DESIGNED
MICROFLUIDIC DEVICES AND IT'S
SHOWN WITH OUR MICROVASCULATURE
ON THE MICROCHIP DEVICES AND WE
LOOKED AT THE WHOLE BLOOD
SAMPLES AND IT CAN USE SIGNAL
FROM FLUORESCENT MICROSCOPY TO
AUTOMATICALLY CREATE A DETAILED
MAP OF DEVICE CHANNELS AS SHOWN
ON THE LEFT OF THE SLIDE.
AND OCCLUSION HAS FLUORESCENT
MICROSCOPY IMAGES AND WHAT
ACCUMULATION IS FOR THIS IS
CALCULATED AS THE CHANGE IN
FLUORESCENT MICROSCOPY IMAGE
AREA RELATIVE TO THE PREVIOUS
FRAME.
ACCUMULATION RATES AND OCCLUSION
WON'T CHANGE BUT IT ALLOWS FOR
THE STUDY OF OCCLUSION OR
THROMBUS INSTABILITY AND DATA
FROM THE SHED AN OVER ALL
DECREASED PERCENTAGE OF OCCLUDED
CHANNELS AND LOOKING AT THE
COMPARISON TO CONTROL.
SO THIS IS A LITTLE BIT
DIFFERENT MICROFLUIDIC SYSTEM
AND THIS IS AN ENDOTHELIALIZED
MICROFLUIDIC SYSTEM UTILIZED BY
SOME MEMBERS OF OUR LAB WITH A
HYDRO GEL AND ALLOWS FOR THE
RECAPITULATION OF THE MEMBRANE
DEPOSITION AND THE BARRIER
FUNCTION AND THIS SYSTEM CAN BE
SUSTAIN FOR LONGER THAN ONE
MONTH SO OBVIOUSLY THAT'S UNLIKE
OTHER MICROVASCULATURE ON A CHIP
DEVICE FOR SINGLE OR SHORT-TERM
EXPERIMENTS.
THIS MICROSYSTEM ENABLES THE
REAL-TIME OBSTRUCTION AND
PERMEABILITY UNDER FLOW
CONDITIONS.
ON THE LEFT YOU CAN SEE THE TIME
LINE FOR THIS HYDRO GEL
EXPERIMENT OR BASELINE
PERMEABILITY WAS CHECKED AT DAY
14 AND PROFUSION OF CELLS AND
FOLLOWED BY MEASUREMENTS AFTER
THE SICKLE CELL PROFUSION HAD
COMPLETED.
YOU CAN SEE THE IMAGES ARE THE
MICROCHANNELS OCCLUDED BY SICKLE
CELLS STAMPED WITH THE WHITE
ARROWS AND THE RESULTING
CO-LOCALIZED ENDOTHELIAL
PERMEABILITY AND LEAKAGE ON THE
TAGGED VSA AS SHOWN OVER HERE.
SO THIS SLIDE SHOWS SOME IMAGES
OF BLOOD SMEARS REVEALING TWO
EXPERIMENTAL SCENARIOS INVOLVING
SICKLE CELL PATIENT BLOOD
SAMPLES AND THE AIM OF THIS
EXPERIMENT WAS TO ASSESS THE
ALTERATIONS AND ENDOTHELIAL P
PERMUTATION AND IT'S
HYPOTHESIZED A LOWER MESSAGE OF
ISCs WOULD NOT LEAD TO
PERMEABILITY CHANGES WHILE THE
HIGHER PERCENTAGE WAS 14% WOULD
LEAD TO OCCLUSION OR INCREASED
PERMEABILITY AND HERE YOU SEE
EPIFLUORESCENT IMAGES THAT
SHOWED PROFUSION OF THE LOW
PERCENT ANG OF ISCs CAUSED NO
CHANGE IN PERMEABILITY IN THE
ENGINEERED HYDRO GEL DEVICES.
AND RESULTS FROM THE HIGH ISC
DEVICES SHOWN ON THE BOTTOM
SHOWED THAT PROFUSION OF THE
ISCs SHOWED TEMPORARY
MICROCHANNEL OCCLUSION AND WE
SAW THERE WAS ENOUGH TO INDUCE
LOSS OF ENDOTHELIAL BARRIER
FUNCTION AND INCREASED
PERMEABILITY SEEN HERE FROM DAY
15.
WITHIN ONE DAY OF CONTINUED
CULTURE AND PROFUSION THE IFC
MICROCHANNEL WAS ABLE TO HEAL
AND GRADUALLY REGAIN ITS BARRIER
FUNCTION WHICH YOU CAN SEE DOWN
HERE IN 16 AND THIS IS JUST
QUANTITATIVELY SHOWN IN THE
GRAPH OVER HERE ON THE RIGHT.
OF COURSE WE'D WANT TO KNOW WHAT
IS GOING ON WITH THE ENDTHELIUM
BEFORE AND AFTER OUR
MICROFLUIDIC ASSAYS HERE SOME
IMAGING WHERE YOU CAN SEE THE
ENTIRE SURFACE OF A MICROFLUIDIC
DEVICE LINE WITH THE ENDOTHELIAL
CELLS PRIOR TO EXPOSURE TO ANY
COMPONENTS.
BRIEFLY HERE'S SOME OF MY DATA
FROM AN EXPERIMENT DESIGNED TO
QUANTIFY ENDOTHELIAL DYSFUNCTION
FOLLOWING EXPOSURE TO VARYING
AMOUNTS OF ISOLATED SICKLE CELLS
BUT SIMILAR EXPERIMENTS CAN BE
DONE WITH WHOLE BLOOD AS WELL
AND THEY WERE STAINED FOR
DYSFUNCTION AND I RAN DIFFERENT
VARIABLES INCLUDING 100% SICKLE
CELLS AND HEALTHY CONTROLS AND
MIXTURES CONTAINING 5% TO 10%
SICKLE CELL IN PATIENTS AND WE
SEE AN EXPRESSION BASED ON THE
PERCENTAGES OF SICKLE CELLS AND
SUSPENSION.
AND THIS IS JUST SOME OF THE
GRAPH SHOWING THE CUMULATIVE
DATA OF NORMALIZED INTENSITY FOR
FORMAL RUNS.
ONE LAST APPLICATION I'LL SHOW
YOU GUYS IS SUSPENSION VELOCITY
TRACKING.
I-PLOTS CAN HAVE TRACKING
ALGORITHMS TO CREATE
MEASUREMENTS AND THE ALGORITHMS
ADAPT TO VIDEO MICROSCOPY OF
MORE ADVANCED RESEARCH DEVICES
SUCH AS THIS DEVICE DESIGNED TO
DE-OXYGENATE SAMPLES UTILIZED BY
DAVE WOODS' GROUP YOU'LL HEAR
ABOUT IN A LITTLE WHILE AND HERE
YOU CAN SEE THE MEAN AND MAXIMUM
VELOCITY MEASUREMENT OF
SUSPENSION AS OXYGEN TENSION IS
LOWERED FROM 160 TO ZERO.
OBVIOUSLY I'VE PROVIDED A SMALL
TASTE OF THE CAPABILITIES OF THE
MICROFLUIDIC DEVICES AND
APPLICATIONS WITH-SICKLE CELL
DISEASE.
I HOPE IT OFFERS AN IDEA
PLATFORM FOR THE STUDY OF SICKLE
CELL DISEASE AND OTHER HEM
HEMOTOLOGIC AND COMBINING THE
USES FURTHER ADVANCE THEIR USE
OUTSIDE THE HYDRO GEL SYSTEM
THEY'RE EASY TO MAKE AND USE
PARTICULARLY NOW WITH THE
ADDITION OF THE DATA ANALYSIS
TOOLS AND TRANSLATIONAL AND
ULTIMATELY SOME CLINICAL
APPLICATIONS WILL BE UTILIZED TO
TRACK CHANGES PRE AND POST
PHARMACOLOGIC INTERVENTIONS
WITHIN THE DEVICES.
SO OBVIOUSLY I DID NOT DISCUSS
ALL OF OUR ASSAYS BUT HOPEFULLY
GAVE YOU A BUFFET OF SOME OF OUR
EXPERIMENTS AND THE MICROFLUIDIC
TECHNOLOGIES AND I'D BE HAPPY TO
ANSWER MORE QUESTIONS VIA THE
CHAT OR E-MAIL AT A LATER TIME
AS WELL.
I'D LIKE TO THANK ALL THE
MEMBERS OF THE LAB AND FOR THE
CONTRIBUTIONS TO THE WORK
PRESENTED HERE.
>> THANK YOU, CHRISTINA.
CAN YOU SEE THE QUESTIONS IN THE
CHAT?
THERE'S ONE ABOUT WHETHER YOU
USED ECs FROM PATIENTS WITH
SICKLE CELL DISEASE FROM
DR. GUPTA.
FOR ALL THE EXPERIMENTS THE
ENDOTHELIAL CELLS ARE UMBILICAL
VEIN ENDOTHELIAL CELLS SO OUR
GOAL WAS TO GET A BASELINE WITH
AN ENDOTHELIAL CELL AVAILABLE
AND TYPICALLY BEHAVES WELL.
WE USED TYPES FROM LARGE VESSELS
SUCH AS HAYEX AND CARDIAC AND
LUNG AND EPITHELIAL CELLS BUT
NONE OF THESE HAVE BEEN
ENDOTHELIAL CELLS FROM SICKLE
CELL PATIENTS BUT SOMETHING
WE'RE INTERESTED IN PURSUING IN
THE FUTURE.
>> SOUNDS LIKE THE NEXT QUESTION
WILL BE ADDRESSED BY DR. WOOD IN
HIS TALK.
>> ANY RUN DIDN'T MEASURE P
SELECTINS SINCE IT BINDS AND
BLOCKING HAS THERAPEUTIC EFFECT?
FOR THE INITIAL REASON WE DID
VCAM AND ESELECTIN WAS MORE SO
THEY WERE TRIED AND TRUE MARKERS
AND ACTUALLY WE KIND OF WERE
STARTING THIS BEFORE P SELECTIN
WAS I THINK BECOMING FAR MORE
INTERESTING IN THE SICKLE CELL
WORLD AND WE CAN ONLY REALLY USE
IT WITHIN THAT PARTICULAR ASSAY
TO BIOMARKERS AND STAIN FOR TWO
THINGS AT A TIME BUT WE'RE
REALLY LOOKING FOR ADDITIONAL
WAYS AND WE LOOKED INTO RNA SEQ
TO GET MORE COMPARED TO MARKERS
OF INFLAMMATION DYSFUNCTION.
DO I HAVE TIME FOR MORE?
IN THE HYDRO GEL DOES IT
DISTEND?
IT HAS ABILITY TO ADJUST SIMILAR
TO WHAT WE WOULD EXPECT WITH IN
VIVO AND WITH ACTUAL BLOOD
VESSELS.
OUR SMALLER PDMS-BASED SILICONE
DEVICES WE DON'T HAVE THE
ABILITY.
IT'S A MORE ADVANCED SYSTEM BUT
NOT WITHOUT ITS CERTAINLY TRICKY
AND DEFINITELY NEEDS A FAR MORE
SKILLED USER AND DOESN'T ALLOW
FOR THAT QUICK AND DIRTY
MICROFLUIDIC EXPERIMENT AS WITH
OTHERS.
YES, THAT IS ONE OF THE GREAT
THINGS ABOUT THAT SYSTEM.
>> AND THE QUESTION ABOUT LARGE
VESSEL EVs FOR ADHESION.
>> I HAVEN'T -- IT'S BEEN A
MINUTE SINCE I'VE DONE WORK AND
WE HAVE AN AORTIC ENDOTHELIAL
CELLS AND LOOKED AT DYSFUNCTION
WITH ESELECTIN AND HADN'T LOOKED
AT ADHESION WITHIN THOSE SYSTEMS
AS WELL AS LOOKING AT THE
ENDOTHELIAL CELLS AND SOMETHING
WE HOPE TO LOOK FOR IN THE
FUTURE.
>> THANK YOU.
THE OTHERS WERE JUST COMPLIMENTS
YOU CAN SEE LATER.
>> THANK YOU.
AND I'M HAPPY TO INTRODUCE
ANOTHER EMORY COLLEAGUE
DR. ROBACK FOR OUR NEXT TALK SO
THANK YOU ALL AGAIN.
>> GREAT.
THANK YOU.
I'LL TRY TO SHARE MY SCREEN.
CAN YOU SEE MY SCREEN?
>>
>> YES, LOOKS GOOD.
>> GOOD.
I'LL GO TO PRESENTATION MODE.
OKAY.
FIRST I'D LIKE TO THANK VIVIEN
AND THE ORGANIZERS FOR GIVING ME
THE OPPORTUNITY TO PRESENT HERE.
THE WORK I'M GOING TO BE TALKING
ABOUT TODAY WAS DONE IN
COLLABORATION WITH JOHNS
HOPKINS.
I HAVE NO DISCLOSURES TO MAKE
RELEVANT TO THESE PARTICULAR
STUDIES.
SO WHEN YOU LOOK AT THE TYPICAL
PATIENTS THAT WE TRANSFUSE, YOU
CAN DIVIDE THOSE PATIENTS A FEW
DIFFERENT WAYS BASED ON WHETHER
THEY HAVE ACUTE RED CELL NEEDS
OR CHRONIC TRANSFUSION NEEDS AND
WHETHER THEY CAN BE SERVED
APPROPRIATELY WITH ROUTINE
MATCHES OR WHETHER THEY REQUIRE
COMPLEX MATCHING ALGORITHMS TO
GET THE MOST COMPATIBLE BLOOD.
THE MORE COMPLEX PATIENTS ARE
SHOWN HERE WITH THE GRAY
BACKGROUND BUT AMONG THOSE,
SICKLE CELL PATIENTS ARE
PROBABLY SOME OF THE MOST
COMPLEX PATIENTS WE MANAGE IN
THE BLOOD BANK IN TERMS OF
PROVIDING RED CELLS FOR
TRANSFUSION BECAUSE OF THEIR
SIGNIFICANT PROPENSITY TO MAKE
RED CELL ALLO ANTIBODIES WHEN
TRANSFUSED AND THEY'RE
TRANSFUSION NEEDS MAY BE BETTER
SUPPORTED BY NOVEL CULTURED RED
CELL PRODUCTS WHICH COULD ONE,
PREVENT ALLO IMMUNIZATION AND
COULD ALLOW YOU TO MAKE RED
CELLS AVAILABLE FASTER BECAUSE
SOMETIMES IT CAN TAKE LONGER
DAYS OR LONGER TO FIND
COMPATIBLE PATIENTS FOR A
PATIENT HEAVILY ALLO IMMUNIZED
AND CAN PREVENT REACTION IN
PREVIOUSLY ALLO IMMUNIZED
PATIENTS.
AND THERE'S THREE APPROACHES
USEFUL FOR TRANSFUSION.
SO THE FIRST APPROACH IS TO
TAKE PRIMARY CD34 STEM CELLS AND
STIMULATE THEM TO DIFFERENTIATE
INTO ERYTHROBLASTS AND
PROLIFERATE BUT THE PRIMARY
ERYTHROBLASTS HAVE LIMITED
SELF-RENEWAL PROPERTIES AND AT A
POINT CHANGE THE CULTURE MILIEU
TO DIFFERENTIATE INTO MATURE RED
CELLS.
MOST ARE PROBABLY AWARE OF A
PAPER PUBLISHED ABOUT 11 YEARS
AGO IN BLOOD WHERE THIS WAS DONE
AND THE RESULTING ERYTHROCYTES
WERE TRANSFUSED AND THE
PERSISTENCE WAS MONITORED AS
WELL AS OTHER OUTCOMES.
THE PROBLEM IS IT'S A FAIRLY
INEFFICIENT APPROACH AND LED TO
ALTERNATIVE WAYS TO CREATE
CULTURES THAT COULD MUCH MORE
EFFICIENTLY PRODUCE LARGE
NUMBERS OF ETHERCYTES FOR
TRANSFUSION.
I'M SHOWING ONE REFERENCE HERE
FROM A GROUP THOUGH THERE'S
DOZENS OF REFERENCES IN THE
LITERATURE AND ESSENTIALLY
ANOTHER WAY TO DO THIS IS TO
TAKE CD34 POSITIVE CELLS OR
ERYTHROBLASTS AND CAUSE THEM TO
DEDIFFERENTIATE TO PROLIFERATE
EXTENSIVELY AND CAN BE
STIMULATED TO RESUME
DIFFERENTIATION OF ERYTHROBLASTS
AND MATURE CELLS AND SO I CAN
COMPARE AND CONTRAST I'M USING
THIS VERY SIMPLE DIFFERENTIATION
SCHEMATIC FROM PLURIPOTENT STEM
CELLS INTO RETICULOCYTES AND
STEM CELLS AND THE WAY I SEE THE
APPROACH THE WAY LIN GAO'S GROUP
HAS DONE IT IS TAKE PERIPHERAL
BLOOD SAMPLES AND DIFFERENTIATE
INTO ERYTHROBLASTS ONCE WE HAVE
PRIMARILY ERYTHROBLASTS IN
CULTURE WE NUCLEOAFFECT THE
CELLS WITH THE OTHER FACTORS TO
STIMULATE THE CELLS TO
DEDIFFERENTIATE INTO PLURISTEM
CELLS TO PROLIFERATE EXTENSIVELY
AND WE CAN LATER CHANGE THE
CULTURE CONDITIONS TO STIMULATE
THEM TO DIFFERENTIATE INTO RED
CELLS.
THIS APPROACH KIND OF WORKS BUT
AT LEAST IN OUR HANDS AND IN LIN
GAO'S HANDS WASN'T THAT
EFFICIENT HERE'S A COMBINATION
OF UNPUBLISHED WORK IN OUR LAB
AND PUBLISHED WORK FROM LIN G
GAA'S CELL AND YOU CAN SEE THAT
YOU START TO GET INCREASED
EXPRESSION OF CD235A ON THE
CELLS AND FEW ARE ENUCLEATE.
YOU CAN MAKE A LOT OF CELLS
USING THIS APPROACH BUT NOT A
GREAT WAY TO CREATE MATURE RED
CELLS THAT CAN BE USED FOR
TRANSFUSION.
AND THERE WAS A SEARCH FOR A
GOLDILOCKS GENE THAT CAN ALOUSE
THEM TO PROLIFERATE MUCH MORE
EXTENSIVELY THAN THEY OTHERWISE
WOULD.
FOR EXAMPLE, IN THE PRIMARY CELL
CULTURE EXAMPLE ALLOW THEM TO
PROLIFERATE MUCH MORE
EXTENSIVELY THAN NORMAL BUT
STILL ALLOWS THEM TO RELATIVELY
EFFICIENTLY BE DIFFERENTIATED
INTO MATURE ERYTHROCYTES.
AND TO COMPARE AND CONTRAST THAT
WITH THE IPSC APPROACH WHICH IS
IN GRAY I SHOWED A COUPLE SLIDES
AGO AND WHAT YOU LOOK AT IS
TAKING ERYTHROBLASTS IN THE SAME
CULTURES AND THEN INTRODUCING A
GENE THAT CAUSES THE
ERYTHROBLASTS TO CONTINUE
PROLIFERATE EXTENSIVELY AND WE
CALL THESE EXTENSIVELY EXPANDING
ERYTHROBLASTS AND STIMULATING
THEM TO DIFFERENTIATE INTO
RETICULOCYTES AND MATURE RED
CELLS.
WHAT I'LL TALK ABOUT IS THE
INTRODUCTION OF BMI-1 IN THE
CELLS.
MUCH OF THE WORK I'LL BE SHOWING
YOU WAS PUBLISHED LAST YEAR AND
LOU ET AL. MOLECULAR THERAPY AND
THERE WAS A MOUSE MODEL WHERE
THEY INTRODUCED BMI-1 INTO
ERYTHROBLASTS IN A MOUSE MODEL.
JUST TO GIVE A SMALL BACKGROUND
ON BMI-1, IT'S ALSO KNOWN AS
PCGF4 PART OF THE POLY CHROME
REPRESSIVE ORIGINALLY FOUND IN
DROSOPHILA ESC AND CAN
UBIQUINATE AND LEAD TO ITS
DEGRADATION WHICH THEN LEADS TO
AFFECTS ON TRANSCRIPTION AND BMI
KNOCKOUT HAS BEEN DONE AND YOU
GET A HYPER CELLULAR MARROW AND
THEY HAVE LIMITED REPOPULATING
ACTIVITY AND THIS FIGURE WAS
TAKEN FROM A REVIEW ARTICLE A
FEW YEARS AGO.
IN ORDER TO INVESTIGATE WHETHER
BMI-1 TO WHAT EXTENT BMI-1 PLAYS
A ROLE IN HUMAN ERYTHROBLASTS
PROLIFERATION AND
DIFFERENTIATION AND WHETHER
THERE MAY BE A GOLDILOCKS GENE
LIN GAO TALKED ABOUT WE USED THE
FOLLOWING CULTURE SYSTEM AND
HUMAN PERIPHERAL BLOOD WAS
COLLECTED FROM VOLUNTEER DONORS
AND THE PERIPHERAL BLOOD WAS
SUBJECT TO A FIGHT CALLED TO
ISOLATE PBMCs AND THEY WERE
PLACED IN ERYTHROBLAST EXPANSION
MEDIUM WHICH WAS SFPM PLUS THE
FACTOR AND IL3 AND IGF1 AND
LOOKING AT CELL NUMBERS YOU SEE
THE FIRST FIVE DAYS YOU GET A
DECLINE IN CELL NUMBERS IN THE
CULTURES THEN YOU GET A REBOUND
SO BY ABOUT DAY EIGHT YOU RETURN
TO THE STARTING NUMBER AND SEE
PROLIFERATION OF THE CELLS OVER
THE ENSUING WEEK OR 10 DAYS.
THIS IS TWO DIFFERENT BLOOD
SAMPLES FROM TWO DIFFERENT
DONORS.
BOTH FOLLOWING THE SAME KINETICS
AND AFTER DAY 16 YOU GET A
PLATEAU AND DECLINE.
LOOKING AT JUST TWO TIME POINTS,
DAY 12 AND DAY 32, BOTH OF WHICH
HAVE SIMILAR CELL NUMBERS IN THE
CULTURES, YOU CAN SEE AT DAY 12
THEY'RE LARGER PLASTIC LOOKING
CELLS AND THEY LOOK
SIGNIFICANTLY MORE HEALTHY THAN
THESE CELLS WHERE THEY HAVE WHAT
LOOKS LIKE DEAD AND DYING CELLS.
IF YOU DO FLOW IMMUNOPHENOTYPING
USING ALPHA 4 INTEGRIN AND ALSO
BAN 3, VERY COMMONLY USED
COMBINATION OF ANTIBODIES TO
LOOK AT THESE MOSTLY BLASTS AND
BY THE TIME YOU GET TO DAY 32
NOW YOU HAVE MORE CELLS AND YOU
GET MORE ERYTHYROID CELLS.
AT DAY 12 WHEN YOU PUT IN EDU
DOING A FALSE CHASE EXPERIMENT
YOU SEE A LARGE NUMBER OF THE
CELLS INCORPORATED THE ANALOG
INTO THEIR DNA.
COMPARE THAT WITH THE NUCLEI AND
BY DAY TWO THERE'S LESS
INCORPORATION OF THE ANALOG.
THIS IS QUANTIFIED OVER HERE AND
IF YOU LOOK AT AND BY DAY 32
OVER A THIRD OF THE CELLS ARE
EITHER DEAD OR DYING.
SO THE NEXT INVESTIGATIONS
LOOKED AT WHAT KIND OF A ROLE
MIGHT BMI-1 PLAY IN ERYTHROBLAST
EXPANSION?
USING THE SAME CULTURES I SHOWED
ON THE PREVIOUS SLIDE, BMI-1
MESSENGER RNA WAS QUANTIFIED BY
QUANTITATIVE RTPCR AND SEE
RELATIVELY HIGH LEVELS ON DAY 8
AND DAY 16 AND PROGRESSIVELY
DECLINING LEVELS TO HALF THE
STARTING LEVEL OR DAY 8 LEVEL BY
32 DAYS IN CULTURE.
FROM A KINETIC PERSPECTIVE THE
DECLINE IN BMI-1 COULD BE
CONSISTENT WITH A REGULATOR
THAT'S EXPRESSED AT HIGHER
LEVELS EARLY ON WHILE THE CELLS
ARE PROLIFERATING AND THEN
TURNED OFF AS THE CELLS ARE
DIFFERENTIATING.
TO LOOK AT WHAT POTENTIAL ROLE
BMI-1 MIGHT PLAY, TWO DIFFERENT
KNOCK-DOWN VECTORS WERE
PRODUCED.
THESE ARE VECTORS THAT PRODUCE A
SHORT RNA SEGMENT.
ONE TARGETING THIS PARTICULAR
AXON HERE IN THE CODING REGION
AND THE OTHER TARGETING THE
THREE PRIME UNTRANSLATED IN
BMI-1.
YOU CAN SEE DOWN HERE IS AGAINST
THE KNOCKOUT VECTOR AND THE
LEVEL YOU SEE IN CULTURES HIT
WITH THIS VECTOR, WHEN YOU
TRANSDUCE CELLS WITH EITHER OF
THESE OTHER TWO VECTORS ONE
TARGETING THE AXON AND ONE
TARGETING THE TRANSLATOR REGION,
YOU CAN GET APPRECIABLE KNOCKOUT
OF BMI-1 EXPRESSION.
WHAT'S INTERESTING IS IF YOU
LOOK AT PROLIFERATIVE CAPABILITY
OF THE CULTURES, WHEN YOU LOOK
AT THE CONTROL VECTOR HERE
TARGETING GFP IS IN BLUE AND YOU
GET ESSENTIALLY THE NORMAL
PROLIFERATIVE CURVE WE SEE
DIVISIONS OR PROLIFERATION FOR
ABOUT 10 OR 12 DAYS AND THEN A
PLATEAU AND SLIGHT DECLINE.
IF YOU TRANSDUCE THE CELLS WITH
EITHER ONE OF THESE KNOCKOUT
VECTORS YOU GET A SIGNIFICANT
PROLIFERATIVE CAPACITY AND THE
AND NOW JUST TO CONFIRM WE DID A
RESCUE EXPERIMENT ONCE AGAIN
USING THE SAME RETROVIRUSES BUT
THEN IN ADDITION CODE
TRANSDUCING WITH THE KNOCKOUT
VECTORS A RETROVIRAL VECTOR THAT
EXPRESSES A BMI-1 TRANS GENE.
AND THIS DOES NOT INCLUDE THE
THREE PRIME TRANSLATER REGIONS.
IT WOULD ONLY BE THIS KNOCKOUT
VECTOR WHICH TARGETS THE AXON.
ONLY THIS KNOCKOUT VECTOR WOULD
TARGET THIS RESCUE TRANS GENE
BUT NOT THE ONCE TRANSLATED
REGION VECTOR.
WHAT YOU CAN SEE HERE IS THAT
WHEN YOU CODE TRANSDUCE THE
KNOCKOUT VECTOR TARGETING THIS
AREA OF THE VARIOUS WITH THE
BMI-1 TRANS GENE THERE'S NO
IMPACT ON PROLIFERATION BECAUSE
THE KNOCKOUT VECTOR IS TARGETING
BOTH THE INDIGENOUS BMI-1
TRANSCRIPT AND THE TRANSCRIPT
COMING FROM THIS LENGTHY VIRAL
VECTOR.
BUT THE KNOCKOUT VECTOR
TARGETING THE REGION TRANSDUCING
THAT WITH THE TRANS GENE THEN
YOU GET A RETURN TO NORMAL
ACTIVITY BECAUSE THE TRANS GENE
IS NOT GET --TARGETED BY THE
VECTOR AND IT'S PROMISING BMI-1
COULD BE A GENE THAT HAS THE
CHARACTERISTICS WE'RE LOOKING
FOR AS A WAY TO PROLONG AND
ALLOW THE CELLS TO DIFFERENTIATE
INTO MATURE RED CELLS.
WHAT I'M SHOWING HERE THEN ARE
STUDIES TO OVER EXPRESS BMI-1 IN
THE SAME ERYTHROBLAST CULTURES.
THIS IS A SCHEMATIC OF THE
CULTURE SYSTEM.
I TOLD YOU THISSERYY
WE
WE CULTURED THEM FOR EIGHT DAYS
AND THEN WE GREW THE CELLS AT
LEAST 60 DAYS IN CULTURE.
THESE ARE THEN THE EXTENSIVELY
EXPANDING ERYTHROID CELLS AND WE
HAD IMDM AND WHAT YOU CAN SEE
HERE IS THAT THE BMI EXPRESSION
VECTOR LED TO MARKEDLY NOTED
LEVELS AND LOOKING AT PERIPHERAL
BLOOD FROM P152 AND P154
COMPARED TO THE P152
ERYTHROBLASTS WHERE WE USED THE
CONTROL GFP VECTOR SHOWN HERE
WHICH PLATEAUS IN TWO WEEKS IN
CULTURE AND THE CELLS ARE ALL
DEAD BY ABOUT THREE TO FOUR
WEEKS IN CULTURE, BOTH OF THESE
CULTURES WHEN TRANSDUCED WITH A
BMI-1 VECTOR EXPANDED OVER 60
DAYS IN CULTURE.
THEY CONTINUE TO EXPAND.
IN SOME CASES WE CULTURE THE 80
OR MORE DAYS.
IF WE LOOK AT THE ERYTHROBLASTS
AT DIFFERENT TIME POINTS, ZERO,
10, 30 OR 60 THEY LOOK SIMILAR
AND LOOK LIKE ERYTHROBLASTS AND
HAVE A FAIRLY LARGE NUCLEUS AND
SMALL RIM OF BASOPHILIC
CYTOPLASM AND BY DAY SIX THEY
STILL LOOK LIKE ERYTHROBLASTS
AND HAVE NORMAL YOU EUKARY
EUKARYOTECYTES AND IF YOU FOCUS
ON THE TWO PLOTS HERE THIS IS
THE ONE I SHOWED BEFORE SO CD49
VERSUS BAN 3.
YOU SEE WITH THE PROLIFERATING
ERYTHROBLASTS TAKEN AROUND THE
E3 CELLS WHERE WE MOSTLY HAVE
EARLY CELLS EARLY IN THE
LINEAGE, WHEN WE THEN UNDER GO
TERMINAL MATURATION AND CAPTURE
THE CELLS LATER AT DAY 8 OF THE
TERMINAL CULTURATION THERE'S A
DIFFERENT PHENOTYPE.
THIS SHOWS A CYTOSPIN OF THE
CELLS AND A FAIR NUMBER OF THEM
LOOK TO BE ENUCLEATED AND I'LL
SHOW STUDIES IN A COUPLE
MINUTES.
>> IT'S A TWO-MINUTE WARNING.
>> I'LL GET THROUGH THE REST OF
THE SLIDES THEN, SORRY.
WE WERE ABLE TO DO THE SAME
THING USING PERIPHERAL BLOOD
FROM ADULT SICKLE CELL PATIENTS
I'LL SKIP OVER BUT THEY
PROLIFERATE NICELY AFTER BMI-1
TRANSDUCTION.
I'LL ALSO POINT OUT AND SORRY
I'M RUNNING SHORT ON TIME BUT
THESE CELLS WE'RE ABLE TO
EFFICIENTLY KNOCKOUT OR EXPRESS
TRANS GENES AND IN THIS CASE WE
KNOCKED OUT CD 55 WHICH IS THE
CHROMER BLOOD GROUP RECEPTOR AND
WE EXPRESS THE NGF RECEPTOR
OFTEN USED FOR SORTING CELLS AND
THE KEY POINT HERE IS THAT IN
BOTH CASES, THE ENUCLEATION WAS
NOT AFFECTED BY EXPRESSING THE
NGF RECEPTOR.
I MENTIONED WE'D BEEN TWEAKING
OUR MATURATION CULTURES AND WHAT
WE SEE HERE IS THAT AS WE GO
FURTHER DOWN THE MATURATION
PATHWAY, YOU CAN SEE WE START TO
GET MORE AND MORE MATURE LOOKING
RED CELLS BY ABOUT DAY 15.
IF WE GO TO DAY 21 WE SEE NEARLY
80% ENUCLEATION AT THAT POINT.
WE HAVE TAKEN THE CELLS AND
TRANSFUSED THEM AND WE HAVE MICE
THAT HAVE BEEN TREATED AND WHEN
WE TRANSFUSE THEM AT DAY ZERO WE
CAN STILL PICK UP CELLS UP TO
ABOUT SEVEN DAYS OR SO AFTER
TRANSFUSION.
ALBEIT THROUGH LOW LEVELS.
THE CELLS EXPRESS CD285A
DIFFERENTIATING THEM FROM THE
MOUSE RED CELLS.
WE CAN STILL DETECT THE CELLS
SEVEN DAYS OUT AND THE LONGER WE
GO THE MORE THE CELLS ARE
ENUCLEATED AND A COUPLE MORE
SLIDES.
JUST TO SHOW YOU THE CELLS DO
PROLIFERATE EXTENSIVELY.
IF YOU DO MATH ON THIS AND I
WANT TO BE CLEAR, THESE ARE
THEORETICAL CALCULATIONS.
WE HAVEN'T DONE THIS BUT IF YOU
RUN THE MATH ON THIS AND LOOK AT
THE EXTENT OF EXPANSION WITH
SOME OF THE CULTURES, YOU CAN
THEORETICALLY PRODUCE HUNDREDS
IF NOT THOUSANDS OF RED CELL
UNITS FROM ONE OF THESE CULTURES
WHICH IS REALLY EXCITING AND
SUGGESTS THIS COULD BE
POTENTIALLY CLINICALLY USEFUL.
THE CELLS -- IF YOU LOOK AT
THEIR IMMUNOPHENOTYPE FOR
TYPICAL RED CELL ANTIGENS, WHAT
YOU CAN SEE IS THE PHENOTYPE IS
IDENTICAL TO THE RED CELLS OF
THE DONOR.
SO IF YOU DID THIS THIS COULD BE
ETOLOGOUS TO THE DONOR AND
SEEING HEMOGLOBIN F EXPRESSION
IN THE SICKLE CELLS AND MATURED
E3 CELLS FROM SICKLE CELL DONOR
AND COULD PREVENT SICKLING.
>> WE HAVE TO WRAP IT UP.
>> IT LEADS TO INTERESTING
POTENTIAL STRATEGY I'D BE HAPPY
TO TALK ABOUT WHICH IS THAT WE
COULD SUPPORT THE NEEDS OF ALLO
IMMUNIZED OR NEGATIVE SICKLE
CELL DONORS USING THIS APPROACH
BECAUSE THESE TRANSFUSED CELLS
WOULD BE ALLOGENIC AND SHOULDN'T
BE TARGETED BY EXISTING
ANTIBODIES AND IF NEED BE WE CAN
LOOK AT KNOCKOUT OR OTHER
APPROACHES TO FURTHER INCREASE
HEMOGLOBIN F AND REDUCE SICKLING
TO MAKE UP NUMEROUS UNITS AND
FREEZE THEM AND THAW THEM WHEN
YOU NEED THEM.
MY BLAST SLIDE IS MY
ACKNOWLEDGEMENT SLIDE AND
COLLABORATIONS AND FUNDED BY
NHLBI WITH THE GRANT HERE.
>> ONE QUICK QUESTION FROM JOHN
BELCHER.
DO YOU THINK ADDING A VECTOR
WOULD IMPROVE ENGRAFTMENT OF
GENE EDITED FSCs.
>> I THINK IT WOULD BE REALLY
WORTH LOOKING AT THAT, ACTUALLY.
WE'RE JUST SURPRISED HOW LONG
THOSE -- WE'RE SURPRISED HOW
LONG WE CAN GET THOSE CELLS TO
PROLIFERATE THE ONLY QUESTION I
MIGHT HAVE AND NEEDS TO BE ST
STUDIED IS WHETHER THOSE CELLS
WOULD ENGRAPH IN THOSE WAYS
AFTER YOU EXPRESS BMI-1 TO
CONTRIBUTE TO THE ERYTHROID
LINEAGE BUT MAKES SENSE TO
INVESTIGATE.
>> OUR FINAL SPEAKER IS
DR. DAVID WOOD FROM THE
UNIVERSITY OF MINNESOTA.
>> OKAY, EVERYBODY.
CAN YOU SEE MY SLIDES?
>> PERFECT.
>> GREAT.
THANKS, VIVIEN FOR ORGANIZING
THE SESSION.
IT'S BEEN GREAT.
I'M ENJOYING ALL THE TALKS.
THANKS EVERYBODY FOR BEING HERE,
OBVIOUSLY.
I'M GOING TO TALK ABOUT SOME OF
WHAT MY LAB DOES AND TOOLS WE
BUILT I THINK ARE COMPLEMENTARY
AND MEASURE SIMILAR THINGS TO
SOME OF WHAT YOU HEARD ABOUT BUT
MAYBE IN A SLIGHTLY DIFFERENT
WAY OR TO TRY TO MEASURE
DIFFERENT ASPECTS OF THE CELLS
BIO MECHANICAL PROPERTIES.
I'M GOING TO START BY THANKING
PEOPLE SO I DON'T FORGET OR RUN
OUT OF TIME AT THE END.
SO MOST THE WORK I'M GOING TO
SLOW YOU TODAY AT LEAST FROM MY
LAB WILL BE DILLON WILLIAMS A
GRAD STUDENT AND A TECH IN MY
LAB AS WELL AS JOSÉ VALDEZ AND
FORMER Ph.D.s AND A FORMER
CLINICAL FELLOW IN THE LAB AND
YOU HEARD FROM CHRISTINA EARLIER
SOME OF THE WORK WE HAVE DONE
WITH THE GEORGIA TECH GROUP AND
I'LL SHOW YOU GROUP WITH DEN
JONG AND I WANT TO ACKNOWLEDGE
THE NGH GROUP AND JOHN HIGGINS
AND SHOW WORK WITH THIS GROUP AT
THE BEGINNING.
I WANT TO ACKNOWLEDGE ALL THOSE
FOCUS AND THE FUNDING.
GENERALLY SPEAKING I DON'T NEED
TO TELL ANYBODY SICKLE CELL
DISEASE BUT I WANT TO SAY MY LAB
IS INTERESTED IN PARTICULARLY
MEASURING THE BIO PHYSIC OF
SICKLE CELL DISEASE SPANNING
FROM HEMOGLOBIN POLYMERIZATION
AND DEFORMABILITY IN BIO
MECHANICS AND BLOOD FLOW AND THE
CIRCULATORY SYSTEM AND I'LL TELL
YOU ABOUT SUITES OF PROBES AT
THE CELLULAR SCALE AND WHOLE
BLOOD SCALE AND WHAT KIND OF
THINGS WE CAN MEASURE AT THOSE
DIFFERENT SCALES.
THE FIRST OF THOSE IS A SINGLE
CELL MEASUREMENT.
THIS WAS ALL MOTIVATED BY THE
IDEA OF WHAT YOU WANT TO KNOW
ABOUT THE SINGLE CELLS
ESPECIALLY RED CELLS IN THE
CONTEXT OF ANTI-SICKLING THERAPY
WHETHER IT'S GENE OR HYDROXYUREA
OR SOMETHING LIKE THAT, YOU WANT
TO KNOW HOW MUCH POLYMER THE
CELLS ARE MAKE AND THE RANGE OF
OXYGEN RETENTION THEY'LL BE
EXPOSED TO AS THEY GO THROUGH
THE VASCULATURE.
THIS IS WORK WITH THE NGH GROUP
AND IN PARTICULAR JOHN HIGGINS
AND OTHERS AND THIS IS BUILDING
ON A PLATFORM PREVIOUSLY
DEVELOPED TO MEASURE OXYGEN
SATURATION OF SINGLE RED BLOOD
CELLS.
WE KNOW HEMOGLOBIN POLYMER HAS A
LOWER AFFINITY THAN SOLUBLE
HEMOGLOBIN AND WHEN IT
POLYMERIZES WE SHOULD SEE THE
OXYGEN AS YOU LOWER THE TENSION.
WE USE THE SYSTEM AND THE WAY IT
WORKS FOR A SINGLE CELL YOU
ILLUMINATE IT AT TWO DIFFERENT
WAVE LENGTHS, 410 AND 430 AND
THERE'S DIFFERENT ABSORPTIONS.
IF YOU MEASURE THE OPTICAL
DENSITY AND TAKE THE RATIO OF
THAT IT TELLS YOU WHAT THE
OXYGEN SATURATION OR THE
HEMOGLOBIN IS INSIDE THE CELL.
AND SIMULTANEOUSLY BECAUSE WE'RE
TAKING IMAGES OF THE CELLS, YOU
CAN DO A MORPHOLOGICAL ANALYSIS
AND YOU CAN CONSIDER THIS FREE
DATA AND YOU CAN LOOK AT THE
CELLS AND SAY, DO THEY LOOK LIKE
SOMETHING THAT'S SOLUBLE OR
SOMETHING'S POLYMERIZED.
WHAT WE DID WAS MORE
SOPHISTICATED WAS TRAIN A
MACHINE-LEARNING ALGORITHM TO
DETECT THE DIFFERENCE BETWEEN
THE TWO.
IN A WAY YOU CAN GET THE
SATURATION AND THE MORPHOLOGICAL
CLASSIFICATION SAYING DO THE
CELLS CONTAIN POLYMER OR LOOK
LIKE A SOLUBLE DEFORMABLE CELL?
THE QUESTION IS WHAT CAN YOU DO
WITH THIS MEASUREMENT.
WE HAD A FEW QUESTIONS GOING
INTO THIS.
ONE THING I'LL SAY AT THE
BEGINNING, ALL THE DEVICES THAT
I'M GOING TO SHOW YOU, ALL THE
TECHNOLOGIES, WE HAVE OXYGEN
CONTROL ON THE DEVICE.
SO WE'RE GOING TO BE ABLE TO
TUNE THE OXYGEN TENSION OF THE
RED BLOOD CELLS AND WHEN I'LL
SHOW YOU THE DEVICE IN DETAIL
AND IT HAS A SCHEMATIC OF THE
DIFFERENT LAYERS AND SHOW WHERE
THE OXYGEN CONTROL COMES IN AND
SUFFICE TO SAY ALL THE DEVICES
HAVE THE OXYGEN CONTROL BUILT
INTO THEM.
THIS IS A SICKLE CELL SAMPLE AND
WHAT YOU MEASURE UNDER ROOM
ATMOSPHERE OXYGEN LEVELS.
ALL THE CELLS ARE PRETTY MUCH
FULLY SATURATED WITH OXYGEN.
THE QUESTION YOU CAN ASK IS WHAT
WILL HAPPEN TO THE DISTRIBUTION
OF THE CELL SATURATION AS IT
GOES DOWN IN OXYGEN.
MY NAIVE THOUGHT IS WHAT YOU'D
EXPECT TO SEE IS THIS WILL MOVE
TO THE LEFT BECAUSE THE
SATURATION WILL GO DOWN AS YOU
DECREASE THE OXYGEN AND IF YOU
START MAKING POLYMER INSIDE THE
CELLS AS YOU INCREASE THE AMOUNT
OF POLYMER, YOU'LL SPREAD THIS
DISTRIBUTION OUT.
IT'S GOING TO BROADEN.
YOU WOULD HAVE THIS MONOMODAL
DISTRIBUTION AND IT WOULD
CONTINUE TO BROADEN AND LOWER
AND EVENTUALLY UNTIL YOU GET TO
ZERO OXYGEN.
WHAT HAPPENS IS THAT AS YOU TURN
DOWN THE OXYGEN SO THIS IS THE
8%.
THIS IS ARTERIAL LEVEL OXYGEN
AND YOU FORM A POPULATION OF
CELLS WITH A LOW OXYGEN
SATURATION.
WHAT THIS IS INDICATING IS THAT
THESE CELLS ARE QUITE A LOT OF
POLYMER AND IT DOESN'T BIND
OXYGEN EFFICIENTLY AND THE
SATURATION OF THOSE CELLS IS
DRAMATICALLY LOWER THAN THIS
POPULATION OF CELLS WHICH HAS
LITTLE TO NO POLYMER AND ALL THE
CELLS ARE AT THE SAME OXYGEN
TENSION.
YOU FORM THESE TWO POPULATIONS
OF CELLS AND AS YOU CONTINUE
GOING DOWN IN OXYGEN NOW WE'RE
AT 6%.
THIS IS CAPILLARY LEVELS.
YOU'VE GOT AGAIN THIS POPULATION
THAT HAS A RELATIVELY HIGH
SATURATION AND LITTLE OR NO POLY
AND A RELATIVELY LARGE
POPULATION HERE NOW THAT HAS A
LOT OF POLYMER IN THEM AND AT A
LOWER SATURATION BECAUSE OF THE
PRESENTATION OF THE POLYMER.
WHAT'S HAPPENING IS YOU GO DOWN
IN OXYGEN AND YOU'RE BASICALLY
GETTING A SHARP INCREASE IN THE
AMOUNT OF POLYMER IN SOME OF THE
CELLS.
SO YOU'RE GETTING THIS BIMODAL
DISTRIBUTION OF SOME OF THE
CELLS AND SOME POLYMER AND SOME
WITH NONE.
IT'S NOT WHAT WE EXPECTED TO SEE
AND IT'S INTERESTING AND IF YOU
THINK ABOUT IT FROM A CLINICAL
PERSPECTIVE AND FROM A BIO
PHYSICAL PERSPECTIVE IT'S AN
INTERESTING OUTCOME AND NOT ONE
I PREDICTED AND THERE'S
INTERESTING QUESTIONS BUT FROM A
CLINICAL PERSPECTIVE IT'S A NICE
MEASUREMENT BECAUSE IT MEANS
THERE'S TWO POPULATIONS HERE.
THIS IS WHAT WE'VE CONSIDERED
THE BAD POPULATION.
WE DON'T WANT THE CELLS THERE AT
ALL.
WE DON'T WANT TO SEE THESE AT
ANY OXYGEN TENSION.
AN EASY MEASURE OF A THERAPEUTIC
EFFECT IS TO ASK HOW MANY CELLS
ARE IN THIS POPULATION VERSUS
THIS AT ANY GIVEN OXYGEN TENSION
AND SHIFT THAT WITH THE THERAPY
AND SHIFT CELLS FROM THE
POPULATION TO THIS ONE BY
APPLYING AN ANTI-SICKLING
THERAPY OR ANTI-POLYMERIZATION
THERAPY AND WE'VE BEEN FORTUNATE
TO PARTICIPATE OR MAKE
MEASUREMENTS FROM THE BLOOD
SAMPLES FROM THE GENE THERAPY
TRIAL AT BOSTON CHILDREN'S
HOSPITAL THEY'RE DOING A VECTOR
TO SILENCE BCL11A AND MAKE
HEMOGLOBIN F.
WE RAN THIS EXACT ASSAY ON A LOT
OF THOSE PATIENTS WHO WERE
UNDERGOING THE GENE THERAPY.
AND I'M GOING TO START YOU OUT
WHICH IS TO SAY THAT ONE OF THE
THINGS THAT'S INTERESTING IS IF
YOU COMPARE THIS GENE THERAPY
POPULATION TO THOSE TREATED WITH
HYDROXYUREA THE GENE THERAPY
PATIENTS AREN'T COMING TO IN THE
HOSPITAL WITH OCCLUSIONS WHILE
THE HIYDROXYUREA PATIENTS ARE AD
IT'S YOU CAN SAY IT'S DUE TO UGF
BUT THERE'S A POPULATION OF THE
HYDROXYUREA PATIENTS NOT MAKING
A LOT OF HBF AND THERE'S A
POPULATION MAKING A LOT AND
COMPARABLE TO WHAT THE GENE
THERAPY PATIENTS ARE MAKING AND
THEY'RE NOT DIFFERENT
STATISTICALLY.
THE TWO POPULATIONS BASED ON HBF
ALONE AND WHEN WE ASK WHAT'S THE
FRACTION OF THE RED BLOOD CELLS
THAT DON'T MAKE POLYMER AND I
HAVE THIS AT TWO DIFFERENT
OXYGEN TENSIONS AND WHEN WE ASK
THE SIZE OF THE POPULATION WE
SEE A DIFFERENCE.
WE'RE SEEING THE BCL11 TREATED
PATIENT MAKING LESS POLYMER THAN
THE HIGH PATIENTS.
AND SO JUST TO SHOW YOU THAT
THERE REALLY IS A DIFFERENCE IN
THIS FUNCTIONAL VERSUS THE PLAIN
MOLECULAR READOUT AND IF YOU
MEASURE THE F CELLS IT GOES THE
OPPOSITE DIRECTION OF WHAT YOU
EXPECT.
IT GETS MORE COMPLICATED.
NEITHER OF THE BASIC MOLECULAR
MEASUREMENTS CAN GIVE YOU WHAT
YOU CAN GET FROM READING FROM
THE POLYMERIZATION.
WE UNDERSTAND WHERE THE DATA'S
COMING FROM AND WE'RE PREPARING
THAT NOW BUT FOR PURPOSES OF
TIME I'M NOT GOING TO THAT HERE
AND GOING TO TALK ABOUT IT
LATER.
THERE'S IMPLICATIONS OF THIS.
WHAT'S INTERESTING IS THE MOST
BASIC ONE IS I THINK THE IDEA OF
MEASURING HBS POLYMER IS
POWERFUL AND TELLS YOU WHAT YOU
WANT TO KNOW BUT FROM A BIO
PHYSICAL PERSPECTIVE IT'S
INTERESTING TO SEE THE
POLYMERIZATION SEEMS TO BE THE
ALL OR NOTHING PHENOMENON ACROSS
A PHYSIO LOGICALLY RELEVANT
RANGE OF ELEMENTS.
IF THAT'S TRUE, IF SOME OF THE
CELLS HAVE A LOT OF POLYMER AND
SOME HAVE NONE IF YOU MEASURE
THE DEFORMABILITY YOU SHOULD SEE
THE BI-DIRECTIONAL DEFORMABILITY
AND THERE'S CLEVER STUFF GOING
UPON I'LL SHOW A SLIGHTLY
DIFFERENT EASY UNDER CONTROLLED
HIYPOXIA AND THIS IS DIFFERENT
FROM THE EAK TA
EKTACYTOMETRY EARLIER AND WE'RE
GOING TO USE HYDRO DYNAMIC
SQUEEZING AND OUR GOAL IS FOR
THE CELL NOT TO TOUCH THE WALL
OF THE DEVICE AND ONLY WANT THE
FLUID TO SQUEEZE THE CELL SO WE
ONLY MEASURE CELL DEFORMABILITY
AND NOT INTERACTIONS WITH THE
WALLS.
THERE'S DIFFERENT REASONS TO
WANT TO MEASURE THOSE BUT FOR
OUR PURPOSES WE ONLY WANT TO
MEASURE PERMEABILITY.
A DEFORMABLE CELLS GOES THROUGH
AND POLYMERIZED CELL GOES
THROUGH AND NOTHING HAPPENS TO
IT AND THAT'S WHAT WE EXPECT TO
SEE HERE.
AS WITH MOST CHIPS WE HAVE AN
ELABORATE SET UP WITH A CAMERA
AND MICROSCOPE AND CAN TUNE IN
THE OXYGEN TENSIONS OF THE CELLS
SO WE KNOW EXACTLY WHERE THEY'RE
AT.
I DON'T NEED TO GO INTO TOO MUCH
HERE AND THERE'S AN AREA OVER
PERIMETER MEASUREMENT MUCH THE
CELLS TO GIVE A MEASURE OF
DEFORMABILITY.
HOW MUCH YOU CHANGE THAT AREA
AND IT'S A MEASURE OF
DEFORMABILITY.
IT'S A HUGE MEASUREMENT AND HOW
MUCH DOES SHAPE CHANGE WHEN IT
GETS SQUEEZED.
IF WE MAKE THE MEASUREMENT
ACROSS A RANGE OF OXYGEN
TENSIONS WE SEE WHAT WE SHOWED
WITH THE SATURATION MEASUREMENT.
21% YOU GET THIS MONOMODAL
DISTRIBUTION WHERE ALL THE CELLS
ARE KIND OF YOU HAVE A RANGE OF
DEFORMABILITIES WHICH IS NOT
USUAL.
THAT'S WHAT WE'D EXPECT AS SOON
AS WE START GOING DOWN IN OXYGEN
WE SEE THE SUBPOPULATION SHOW UP
WITH A LOW DEFORMABILITY AND
WHAT'S INTERESTING AND THAT
POPULATION OF CELLS GROWS AS YOU
DROP OXYGEN WHILE THE HIGH
DEFORMABILITY POPULATION SHRINKS
AS YOU DROP THE OXYGEN TENSION.
WHAT'S INTERESTING HERE AND THIS
IS MAYBE EVEN CLEARER THAN WITH
THE OXYGEN SATURATION
MEASUREMENT, IF YOU LOOK AT THE
MEDIAN OF THIS PEAK HERE IT'S
NOT REALLY CHANGING AS WE DROP
THE OXYGEN TENSION WHICH KIND OF
IMPLIES THE AMOUNT OF POLYMER IN
THE CELLS ISN'T CHANGING OR AT
LEAST THE AMOUNT THE LEVEL OF
DEFORMABILITY ISN'T CHANGING AS
WE DROP THE OXYGEN TENSION
THEY'RE ABOUT AS STIFF AS THEY
WERE WHEN THEY FIRST POLYMERIZED
OR FIRST FORMED POLYMER.
THAT'S REALLY INTERESTING.
THIS IS JUST ONE SAMPLE BUT OF
COURSE YOU CAN MEASURE ACROSS A
RANGE OF BLOOD SAMPLES FROM
DIFFERENT PATIENTS AND YOU SEE
THE SAME THING ACROSS ALL OF
THEM WITH THIS BIMODAL
DISTRIBUTION AND YOU SAY IF YOU
CAN MEASURE WHY AND SATURATION
WHY NOT BOTH AND THIS IS A QUICK
DEMONSTRATION THAT WE CAN DO
THAT TOO AND LOOK AT THE
DIFFERENT OXYGEN TENSIONS AND
IT'S WELL CORRELATED.
I THINK THIS HAD SOME PRETTY
IMPORTANT IMPLICATIONS.
SO WE DO SEE THERE'S TWO
DISTINCT MECHANICAL POPULATIONS
OF RED CELLS IN SICKLE CELL AND
I THINK THE RELATIVE FRACTIONS
OF THE TWO POPULATIONS IS REALLY
A GREAT COMPLICATION FOR ANY
KIND OF ANTI-SICKLING THERAPY
INCLUDING GENE THERAPY.
I ALSO THINK AND I THINK
CHRISTINA'S DATA HIGHLIGHTS THIS
REALLY WELL THE PRESENCE OF THE
STIFF CELLS EVEN A SMALL
POPULATION HAVE HIGH ARTERIAL
OXYGEN TENSIONS TO ME HAS
IMPLICATIONS FOR CONTINUOUS
VASCULAR DAMAGE AND YOU CAN'T
AVOID THAT ONCE YOU SEE THE
CELLS ARE AROUND AT ALL OXYGEN
TENSIONS.
AND I'LL ALSO SAY AND THIS IS
ANOTHER INTEREST OF MINE IS THAT
THAT DISTRIBUTION OF MECHANICAL
PROPERTIES WILL DRIVE ALTERED
BLOOD FLOW.
SO I'LL QUICKLY TRANSITION TO
THIS AND PROBABLY NOT SHOW IT
ALL IN THE INTEREST OF TIME BUT
A REMINDER SICKLE BLOOD FLOW IS
IMPAIRED UNDER HYPOXIC
CONDITIONS AND THIS IS SICKLE
BLOOD FLOW UNDER NORMAL
CONDITIONS AND THIS IS WHAT IT
LOOKS LIKE WHEN YOU TAKE OUT THE
OXYGEN.
I LIKE TO SHOW THE VIDEO BECAUSE
IT GIVES PEOPLE A SENSE OF HOW
DRAMATIC THE CHANGE IS FROM THIS
TO THIS WHEN YOU TAKE THE OXYGEN
WAY.
THE CELLS ARE MORPHOLOGICALLY
DIFFERENT AND THE BLOOD COMES
ALMOST TO A COMPLETE STOP AND
YOU CAN CONTROL THE BLOOD FLOW
AND THE CONTROL HYPOXIA HAS OVER
SICKLE CELL DISEASE AND WE
CREATE THE DEVICES TO LOOK AT
THIS UNDER WELL CONTROLLED
OXYGEN TENSION AND THAT'S ON
THIS SLIDE.
WE HAVE A BLOOD LAYER AT THE
BOTTOM SHOWN IN RED HERE.
WE HAVE A HYDRATION LAYER AND
THE TOP WE HAVE A GAS LAYER
WHERE WE CAN FLOW GAS WITH
CONTROLLED OXYGEN TENSION AND IT
CAN DIFFUSE AND THAT'S HOW WE
CONTROL OXYGEN AND AGAIN WE CAN
CONTROL IT PRECISELY AND WHAT
OXYGEN TENSION THE CELLS ARE
SEEING.
I'VE GOT TWO MINUTES HERE.
AND WE CAN MEASURE THE OXYGEN
FIELD AND HIGHER RESOLUTION BUT
SOME COOL STUFF YOU CAN DO WITH
THIS BECAUSE WE HAVE HIGH
RESOLUTION VELOCITY FIELDS YOU
CAN LOOK AT THE PROPERTIES OF
BLOOD FLOW AND THAT'S IMPORTANT
IF WHAT YOU WANT TO DO IS
EXTRAPOLATE THAT TO LARGER
VESSELS AND WE'VE MEASURED THE
BLOOD UNDER THE CONDITIONS AND
SIMULATE WHAT THE BLOOD FLOW
WOULD LOOK LIKE AND THIS IS
TAKEN FROM MRI IMAGES AND
COMPUTING THE BLOOD FLOW BASED
ON WHAT WE MEASURE AND YOU CAN
DO THINGS LIKE PREDICT WHAT THE
WALL SHEER STRESS MIGHT BE AND
CAN IMPROVE WHEN YOU TREAT A
PATIENT WITH A TRANSFUSION.
I WON'T GO INTO THIS BUT TO SAY
OTHER THINGS YOU CAN DO IS
THERE'S A NICE STUDY WE'VE DONE
WHERE YOU CAN TAKE BLOOD FROM
PATIENTS AND TREAT IT AND SEE
THE IMPROVEMENT IN THE BLOOD
FLOW AND SEE THE DRAMATIC
IMPROVEMENT WHEN YOU TREAT WITH
VOXELOTOR AND YOU CAN SEE
INFORMATICS TO SEE WHAT'S
DRIVING THE CHANGES.
WE DID THAT WITH THE SUBSET OF
PATIENTS AND ONE THING YOU CAN
SEE IMMEDIATELY FROM THE HEAT
MAP IS THE SS AND SC PATIENTS
CLUSTER VERY NICELY AND HBC
POSITIVELY CORRESPONDS AND MAYBE
IT SYNERGISTICALLY BINDS.
AND I'LL SAY WE CAN MAKE THESE
MEASUREMENTS IN MANY SCALES.
I THINK THE SINGLE CELL
PROPERTIES ARE REALLY IMPORTANT
IN REVEALING MECHANISMS FOR THE
DIVERSE RESPONSE TO THERAPY WE
SEE AND I THINK IT'S IMPORTANT
TO MAKE THESE FUNCTIONAL
MEASUREMENTS OPPOSED TO JUST
MOLECULAR MEASUREMENTS.
THERE'S A LOT OF WE CAN SAY
ABOUT THE DISEASE PHENOTYPE.
WITH THAT I'LL STOP BECAUSE I
THINK WE'RE OUT OF TIME.
>> YES, BUT THANK YOU SO MUCH TO
ALL THE SPEAKERS.
IT'S A WONDERFUL SESSION.
AND MAYBE WE CAN SQUEEZE OUT ONE
OR TWO QUESTIONS?
>> NO, I DON'T THINK SO.
>> PLEASE E-MAIL THE SPEAKERS IF
YOU HAVE FURTHER QUESTIONS.
>> THANK YOU VERY MUCH.
>> THANK YOU FOR AN EXCELLENT
PANEL OF SPEAKERS AND EXCELLENT
SESSION BUT I THINK WE NEED TO
MOVE ON TO OUR NEXT SESSION.
AND OUR NEXT TWO SPEAKERS ARE
GOING TO TALK ABOUT -- GIVE YOU
A GLIMPSE OF ONE OF OUR FLAGSHIP
PROGRAMS AT NIH CALLED H3 AFRICA
PROGRAM FOR HUMAN HEREDITY AND
HEALTH IN AFRICA.
I'M SURE MANY ARE AWARE OF THE
PROGRAM.
IT'S TO FACILITATE AN
AFRICAN-BASED RESEARCH APPROACH
TO LOOK AT DETERMINATES OF
DISEASE WITH THE GOAL OF
IMPROVING THE AFRICAN
POPULATION.
IT'S A PROGRAM THAT'S HAD
SUBSTANTIAL INVESTMENT FROM NIH
AND FROM AFRICA AND AFRICAN
RESEARCHERS AND AFRICAN
POPULATIONS.
AND HAS BEEN A TREMENDOUSLY
SUCCESSFUL PROGRAM AND I'D LIKE
THE NEXT TWO SPEAKERS BOTH VERY
DISTINGUISHED SPEAKERS
DR. SOLOMON AQUAH FROM THE DEAN
OF LIFE SCIENCES AT THE
UNIVERSITY OF GHANA AND
DR. AMBROSE WONKAM THE RECENTLY
MINTED PROFESSOR OF GENETICS AND
MEDICINE AT THE DEPARTMENT OF
GENETICS AT JOHNS HOPKINS
UNIVERSITY.
SO I THINK THE FIRST SPEAKER IS
SOLOMON.
IT'S ALL YOURS.
>> YOU HAVE MY SLIDES.
DO I HAVE TO SHOW MY SCREEN?
>> NO, IT'S ON.
>> THANK YOU FOR THE LOVELY
INTRODUCTION.
THANK YOU, COLLEAGUES.
I'M GOING TO TALK TO YOU ABOUT
THE COHORT FOR RESEARCH IN
SICKLE CELL DISEASE.
>> I'M GOING THIS FOR THE SAKE
OF THOSE NOT FAMILIAR WITH IT
AND PARTICULARLY STUDENTS.
WE ALL KNOW IT'S A GENETIC
DISORDER WITH A MUTATION AND
THERE'S A SINGLE POINT MUTATION
IN THE HEMOGLOBIN GENE THAT IS
THE MOLECULAR GENETICS FOR
SICKLE CELL DISEASE.
WE DO KNOW THAT THIS CHANGE IN
THE NUCLEOTIDE LEADS TO A CHANGE
IN THE SEQUENCE WHERE THE ACID
IS SUBSTITUTE AND THE
POLYMERIZATION WHICH WE HEARD
AND GO BACK ONE, AND THE
PRESENTATION ON THE
POLYMERIZATION KINETICS LEADS TO
THE FORMATION OF SICKLE CELL VCs
AND FROM THE BIOLOGICAL POINT OF
VIEW WE KNOW TWO BASIC ANOMALIES
THERE'S THE PROPENSITY TO STICK
TO EACH OTHER.
WE HEARD SEVERAL TALKS ABOUT
POLYMERIZATION.
AS THE TWO CELLULAR ANOMALIES WE
BASICALLY BLAME FOR A VARIETY OF
CLINICAL COMPLICATIONS THAT
AFFECT EVENTUALLY EVERY ORGAN
SYSTEM IN SICKLE CELL PATIENTS.
ABOUT 10 YEARS AGO MY LAB WAS
INTRIGUED BY THE BASIC QUESTION
THEY HAD WAS HOW IT PROMOTES
ACUTE COMPLICATIONS OF SICKLE
CELL DISEASE AND WHAT ARE THE
MECHANISMS.
WE USED MOUSE MODEL TO TRY TO
UNDERSTAND THIS.
OUR INTEREST WAS ON THE STUDY
THAT SHOWED INDIVIDUALS WHO HAVE
THIS AT THE TIME OF PRESENTATION
HAVE A SUDDEN DROP IN HEMOGLOBIN
WHICH WE INTERPRETED TO MEAN
ACUTE INTRAVASCULAR HEMOLYSIS
AND AT THE TIME THE PARADIGM
WITH RESPECT TO BIOLOGY IN
SICKLE CELL DISEASE WAS
INJECTING SICKLE CELL MICE
INTRAPERITONEAL AND THE OUTCOME
WAS QUITE DRAMATIC.
WE DISCOVERED THAT WHEN YOU
INFUSE PURIFIED HEME WITHIN A
SHORT PERIOD THE SLIDE YOU SEE
IS A CONTROL ANIMAL INFUSED WITH
SALINE AND AN EXPERIMENTAL MOUSE
INFUSED WITH A BODY WEIGHT OF
HEME AND YOU SEE CLEAR EVIDENCE
OF THE MASSIVE INJURY TO THE
LUNG OF THE MICE AND WITHOUT
GOING THROUGH EXTENSIVE DETAILS
WE ARE ABLE TO STUDY THIS IN
MORE DETAIL USING A VARIETY OF
TOOLS INCLUDING THE PULSE OX AS
WELL AS MEASURING OXYGEN AND
LOOKED AT GENETICS AND BONE
MARROW EXPERIMENTS TO
DEMONSTRATE CONCLUSIVELY THAT AN
S OF THIS IN THE MOUSE TRIGGERED
CLASSICAL ACUTE LUNG INJURY.
SOW THIS LED US TO DEVELOP A
CONCEPTUAL MODEL THROUGH
HEMOLYSIS AND ACTED THROUGH THE
SIGNALLING CAUSED ACUTE LUNG
INJURY AND THIS WAS REMINISCENT
OF THE RAPIDLY EVOLVING SIN
DROLL THAT COLLEAGUES PROPERTY
REPORTED AND SICKLE CELL DISEASE
PATIENTS WHEN ADMITTED TO THE
HOSPITAL WITH ACS DIE WITHIN 24
TO 72 HOURS AND OUR MOUSE MODEL
WE THOUGHT WAS A GOOD REPLICA OF
THE CLINICAL PHENOM NONE AND IF
THIS WAS -- PHENOMENON AND THIS
WIS ENOUGH TO CAUSE ACUTE
DISEASE THERE'S DEFENSE
MECHANISMS.
THESE INCLUDE HAPTO GLOBIN AND
OTHER MADE NATURALLY ARE AN AND
A HALF DEFENSE MECHANISM TO
PROTECT AGAINST THE DELETERIOUS
AFFECT OF HEME.
WE'VE GONE ON TO DO A LOT OF
STUDIES INCLUDING HEMOPEXIN.
AND WHAT I'LL SHOW WITH RESPECT
TO THE H3 AFRICA PROJECT WE
TRIED TO EXPLORE THE GENETICS OF
THE HEMOLYSIS IN THIS
SICKLEGENAFRICA COHORT.
SO THIS IS ESSENTIALLY THE
CONCEPTUAL FRAMEWORK.
WE APPRECIATE THE HEMOLYSIS CAN
CAUSE NOT ONLY ACUTE INJURY TO
THE LUNG AND AS I'LL SHOW IN A
SECOND, ACUTE INJURY TO THE
KIDNEYS.
WE HAVE DATA AND WE ALSO KNOW NO
PATIENTS HAVE THE SAME HEMOLYSIS
AND THE GOAL OF THE PROJECT WAS
TO UNDERSTAND THE GENOMICS THAT
INFLUENCED THE VARIABLE CAPACITY
AND THIS WAS ORGANIZED WITH THE
GENOMICS OF MODIFYING PROTEINS
AS WELL AS THE CALL FOR THE WORK
AND QUE HAVE COLLABORATORS IN
NIGERIA AND IT'S A
CARDIOVASCULAR PROJECT WHERE FOR
THE FIRST TIME WE GOT ECHOS ON
THE ADULT PATIENTS AND LOOKING
AT WHAT WE FIND IN PROJECT 1.
PROJECT 2 FOCUSSED ON THE
GENOMICS OF SEVERE MALARIA AND
SICKLE CELL PATIENTS.
WE HAD DIFFICULTY IN TERMS OF
THE NUMBER OF PATIENTS.
THAT CHANGED INTO AN EX VIVO
STUDY AND THE BIO INFORMATICS
HAS BEEN DONE IN PITTSBURGH AND
IN CAPE TOWN.
THIS IS WHERE YOU LOOK AT FROM
THE STRUCTURE IN TERMS OF THE
SCIENCE FOR THE SICKLEGENAFRICA
NETWORK.
YOU'RE LOOKING AT THE STUDY
DESIGN OF THE NETWORK.
YOU CAN SEE FROM THE VERY TOP
OVER ALL SICKLEGENAFRICA IS A
PROSPECTIVE OBSERVATIONAL STUDY
OF PROTECTIVE PROTEINS AND
DAMAGE IN SICKLE CELL DISEASE.
WE START WITH AN ETHICS APPROVAL
AND TRAINING OF TO THE STAFF
INVOLVED AND THERE'S SIX
CLINICAL SITES WE ENROLLED
PATIENTS OVER 50 PATIENTS IN
TERMS OF RESEARCH INVESTIGATORS
IN DIFFERENT LEVELS INVOLVED IN
THE PROJECT AND WE'RE MAKING
SURE THE PATIENTS AND THEIR
FAMILIES UNDERSTAND WHAT IT IS
WE WANT TO DO SO ONCE WE GET
APPROVAL AND GET COMMUNITY
ENGAGEMENT DONE AND I'LL SHOW
YOU SLIDES WE BEGAN THE PROCESS
OF ENROLLING PATIENTS.
OUR TARGET WAS TO ENROLL 7,000
SECOND HALF PATIENTS, ADULTS AND
CHILDREN WITHIN THREE YEARS, TWO
TO THREE YEARS.
COVID EXTENDED THAT A BIT AND
YOU CAN SEE THE FLOW DIAGRAM.
AND PATIENTS ENROLLED IF THEY
PRESENT WITH ACUTE ILLNESS THEY
ENROLLED SAMPLES ARE TAKEN.
WE HAVE TO VERIFY EVERY PATIENT
IS ACTUALLY A SICKLE CELL
PATIENT AND WE DO THAT AND YOU
CAN FOLLOW THE ARROW GOING DOWN
TO WHERE WE ARE NOW.
WE ARE ESSENTIAL LY IN OUR STUD.
WE ARE AT THE TAIL END.
AN IMPORTANT COMPONENT IS THE
FRAMEWORK AND WE FOCUS ON
AUTONOMY AND DUTY OF CARE AND
THE PATIENT'S BEST INTEREST.
AND THIS IS LED BY DR. KOFI
ANNAN A CLINICAL PSYCHOLOGIST
AND HAVE DONE COMMUNITY
ENGAGEMENT AND THERE'S ABOUT 20%
OF OUR PARTICIPANTS ARE UNABLE
OR DO NOT GIVE CONTENT AND THEY
SAID THEY'LL SPEAK WITH THEIR
FAMILY AND COME BACK AND THAT'S
IMPORTANT TO RESPECT.
NEARLY 98% OF OUR PARTICIPANTS
WANT RESULTS RETURNED TO THEM
EVEN IF UNRELATED TO THE
RESEARCH QUESTION AND ETHICS SAY
IS A MAJOR PIECE OF WHAT WE DO
ENGAGE THE COMMUNITY ACTIVELY.
THIS IS THE COMMUNITY ENGAGEMENT
WE DID BEFORE WE DRAW THE FIRST
BLOOD SAMPLE.
THIS IS THE PROJECT IN APRIL
2018 AND WHAT YOU SEE HERE ARE
COMMUNITY AND RELIGIOUS LEADERS
AND PATIENTS AND PARENTS TO
DISCUSS WHAT SICKLEGENAFRICA WAS
ALL ABOUT AND TOOK THAT ON THE
ROAD SHOW TO THE SIX
PARTICIPATING SITES.
WE WENT TO GHANA AND THEN WENT
TO LAGOS AND THEN TANZANIA.
AND THIS WAS IMPORTANT TO MAKE
SURE PATIENT AND THEIR FAMILIES
UNDERSTOOD IT IN TERMS OF THE
FACT THERE WOULDN'T BE IMMEDIATE
BENEFIT TO THE PATIENTS IN THE
STUDY AND REGARDLESS OF THAT
THERE WAS A LOT OF ENTHUSIASM
FROM PATIENTS AND PARENTS TO BE
PART OF THE STUDY.
AS OF 2021 WE SURPASSED OUR
ORIGINAL TARGET OF 7,000
PATIENTS.
WE ENROLLED 3,901 CHILDREN.
THE CITIES WITH THE NUMBER OF
PARTICIPANTS THAT HAVE BEEN
ENROLLED AND LOOKING AT THE
CLINIC STARTED IN KUMASI
FOLLOWED BY THE CLINIC IN DAR ES
SALAAM AND ALL RECRUITMENT WAS
WITH RED CUP DATA AND WE
ENROLLED 3,108 ADULTS WHICH HAS
HAD ADULT SICKLE CELL CLINICS
AND THAT'S LEADING THE WAY.
BY NOVEMBER OF LAST YEAR WE
ENROLLED OVER 7,000 PATIENTS
INTO THIS STUDY MAKING IT THE
LARGEST COHORT STUDY OF SICKLE
CELL DISEASE I'M AWARE OF.
JUST A COUPLE OF THINGS.
THIS IS THE ADULT COHORT AND IT
WAS INTERESTING TO US AT THE
TIME OF ENROLLMENT HOW'S
PATIENTS WERE MANAGING THEIR
PAIN.
YOU CAN SEE THE DRUGS PATIENTS
WERE USING TO MANAGE THEIR PAIN.
QUITE INTERESTING IN THE SLIDE
AND WHEN WE LOOKED AT OTHER
MEDICATIONS, I WANT TO POINT TO
TWO MEDICATIONS.
IF WE LOOK AT HYDROXYUREA LESS
THAN 6% WERE ON THIS AND NEARLY
99% WERE TAKEN FOLIC ACID.
IT'S REALLY QUITE INTERESTING
WHEN PATIENTS BELIEVE AND THEY
HAVE ACCESS TO A DRUG THAT CAN
INFLUENCE THEIR DISEASE AS FOLIC
ACID IS BELIEVED IN THIS PART OF
THE WORLD TO HAVE BENEFICIAL
EFFECT THEY TAKE IT AND WHEN THE
DRUG IS UNAVAILABLE AS HYDR
HYDROXYUREA HAS NOT THEY CANNOT
TAKE IT.
IT SPEAKS TO PATIENT'S ATTITUDES
IN TERMS OF MEDICATION.
THEY'LL TAKE THE DRUG AND
WHEN --
>> TWO-MINUTE WARNING.
>> SAY THAT AGAIN?
>> YOU HAVE A TWO-MINUTE
WARNING.
>> OKAY.
NEXT SLIDE, PLEASE.
AND THIS IS TO SHOW YOU WHAT
CONDITIONS WHERE THE PATIENTS
WERE BASICALLY TREATING AT THE
TIME OF ENROLLMENT.
BASED ON THE PREVIOUS SLIDE, THE
MAJORITY OF PATIENTS WERE
TREATED FOR MALARIA.
THERE'S A WIDE VARIATION IN THE
LEVEL.
HERE YOU SEE THE LEVELS OF
HEMOPEXIN AND THE MACROGLOBULIN
AND SOME ARE NEARLY A NORMAL
VALUE AND THE MAJORITY OF SICKLE
CELL PATIENTS ARE LESS AND ONE
FOR THE OTHER IT'S THE OPPOSITE.
BOTH PROTEINS BIND AND DEPENDING
ON WHICH THEY'LL END UP IN THE
LIVER OR KIDNEY.
WE ASKED AND LOOKING AT THE
SEVERITY OF HEMOLYSIS AND WE SAW
A NICE CORRELATION AND TRAINED
THE RATIO AND WE SEE IT BINDS TO
THE KIDNEY AND THIS GIVES
CONFIDENCE TO PROBE FURTHER IN
MICE.
HERE WE ASKED IF THERE'S AN
EXCESS OF HEME IN THE SICKLE
CELL MOUSE WHERE WILL THE HEME
GO?
YOU CAN SEE THE MAJORITY OF THE
EXCESS HEME ENDS UP IN THE
LIVER.
AND EXCESS HEME GOES TO THE
KIDNEY RATHER THAN GOING TO THE
LIVER.
AND WE MEASURED THE FILTRATION
RATE AND YOU CAN SEE AT BASELINE
THE MOUSE MEASURED THE GFR AND
WAITED A COUPLE DAYS AND
CHALLENGED IT WITH HEME.
THERE'S THIS IS A LOW DOSE OF
HEME THAT DOESN'T CAUSE ACUTE
LUNG INJURY BUT YOU WOULD KNOW
IF THE MOUSE HAS BEEN CHALLENGED
AND DOING IT 48 HOURS AFTER THE
HEME CHALLENGE IS NO DIFFERENCE
AND WE CAN SEE A CLEAR
DIFFERENCE THE SS MOUSE HAS AN
IMPAIRED GFR.
AND IMPORTANT TO NOTE THAT WE
BASICALLY FOLLOWED THIS AVENUE
OF RESEARCH QUESTION BASED ON
OUR DATA IN THE SINGLE
SICKLEGENAFRICA COHORT WHERE WE
SAW AN ASSOCIATION BETWEEN
HEMOPEXIN DEFICIENT AND MARKERS
AND CAN DEMONSTRATE WITH MOUSE
MODELS AN EXCESS HEME LEADS TO
ACUTE KIDNEY INJURY AS THE BASIS
FOR ACUTE AKI IN SICKLE CELL
DISEASE.
AND TO SUMMARIZE WE HAVE S WITH
CLINICAL DATA AND BIOLOGICAL
SAMPLES STORED AND 99% OF THE
COHORT HAVE GIVEN BROAD CONSENT
FOR THE USE OF THEIR DATA AND
SAMPLES FOR FUTURE STUDIES.
AND THERE'S INCIDENTAL FINDINGS
WHETHER OR NOT TREATMENT IS
AVAILABLE AND BELIEVE THE STUDY
HELPS TO IDENTIFY SICKLE CELL
DISEASE AS A RISK FACTOR FOR
ACUTE KIDNEY INJURY.
THERE'S A TEACHING HOSPITAL AND
THE INSTITUTIONS IN LAGOS AND
THEN OF COURSE THE HISTORY OF
PITTSBURGH.
YOU CAN SEE THE FUNDING THAT'S
SUPPORTED A LOT OF THIS WORK
OVER THE YEARS.
>> THANK YOU, GREAT TALK.
I THINK THERE'S XENTS ON THE
CHAT BUT YOU CAN RESPOND TO
THEM.
SORRY, WE NEED TO MOVE ON TO
AMBROSE.
HE'S GOING TO TALK ABOUT WHY WE
SHOULD INVEST IN GENOMIC
VARIATION.
DR. WONKAM.
>> THANK YOU FOR THE INVITATION.
TODAY MY ROLE IS SIMPLE.
I
>> LET ME SWAP THE PRESENTERS.
>> AND MANY WERE COLONIZED IN
EUROPE AND ASIA.
IT MADE THE GENOME MORE VITAL IN
AFRICA.
AFRICA FOR EXAMPLE, THE APPROACH
I'M SURE THE EVALUATION WAS NOT
PRESENT.
WE KNOW SOME HAVE BEEN LOOKED AT
AND THEY MOVED TO EUROPE AND TO
ASIA AND WHY IS THIS IMPORTANT?
THIS IS ONE OF THE
PREDISPOSITION THAT ALLOWED
GENETIC DISPOSITION AND THERE'S
ONE PORTION OF WHAT WAS MADE
FROM THE NEANDERTHAL AND THAT
CAN BE BEST INVESTIGATED IN
AFRICAN POPULATION FOR HEALTH
AND DISEASE.
AND ONLY 2% OF AFRICAN ANCESTRY
EXISTED IN GWAS AND THERE'S A
CASE OF THIS VARIANT.
AND THERE'S A DEVELOPMENT IN
VARIANTS WITH MEDICATION AND
ONCE THE VARIANT ASSOCIATED WITH
DIABETES CAN ONLY BE FOUND IN
AFRICA.
THAT MEANS THERE IS TOMORROW A
DRUG DEVELOPMENT AROUND THAT.
AND THERE'S A SERIES FOUND AND
REPLICATED IN 5,000 EUROPEANS
FROM SWEDEN AND DESPITE HAVING
FIVE TIMES LESS SAMPLE SIZE,
AFRICAN SAMPLE MORE LARGER IN
EFFECT AND THAT MEANS WITH MORE
SAMPLE, LARGE GENOMIC VARIATION
ALLOWED TO FIND SOMETHING
IMPORTANT.
I'LL NOW MOVE TO SINGLE GENE
DISORDER.
WE KNOW FOR SINGLE GENE DISORDER
THE PROFILE MAY NOT BE THE SAME.
THE CONDITION MAY KNOW
HUNTINGTON DISEASE AND ONE GENE
IS LOCATED.
ONE OF THE TOPIC OF RESEARCH
HERE WE FOUND THAT THE GENE THAT
EXPLAINS CHILDREN BORN DEF AND
50% WERE FROM AFRICAN ANCESTRY.
WE KNOW FRECH -- THAT THE NEXT
VOLUNTEER ALLOWS FOR INVOLVE
GENE DISCOVERY IN AFRICA AND
SOME FAMILIES DESCRIBE SEVEN
NOVEL GENES.
FOR EXAMPLE, IN THIS FAMILY WE
FOUND THE WAARDENBURG SYNDROME
AND THERE WAS MALFORMATION.
WE WENT BACK TO THE FAMILY AND
FOUND AT LEAST ONE OF THE
EFFECTED PERSON HAD THE
DISTURBANCE.
AND HERE'S WHERE THERE WERE
INVOLVE GENES FOR SOX 9 AND
THERE WAS MALFORMATION.
THIS IS A PROOF OF CONCEPT WE
BELIEVE AND APPLICABLE TO ALL
GENE DISORDER.
AND WE'LL FIND SOMETHING
UNEXPECTED.
WE LOOKED AT THE ALLO
DIFFERENTIATION AND FOUND THAT
THE DIFFERENCE BETWEEN ASSENCESL
IS NOT THE SAME AND THERE'S A
DIFFERENTIATION BETWEEN THOSE
THAT HAVE IT AND NOT SUGGESTING
AFRICAN POPULATION WOULD BE A
GOOD POPULATION TO STUDY AND
APPROPRIATE LANGUAGE BECAUSE IF
WE DON'T HEAR THEY WILL NOT
TALK.
THE REASON REASON WE SHOULD
INVEST IN AFRICAN POPULATIONS
AND THEY'RE NOT ASSOCIATED WITH
THIS DEVELOPMENT AND ALL THE
ELEMENTS, CLIMATE, ENVIRONMENT,
FOOD, INFECTION AND WE ARE
SPEAKING TO SICKLE CELL DISEASE
ONE TYPICAL EXAMPLE OF THE
ENVIRONMENT INVOLVED IN AFRICA
AND WE CAN LOOK AT WHAT IS
ASSOCIATED WITH AFRICAN
POPULATION.
THIS IS IMPORTANT.
WE KNOW AND THE COMBINATION OF
IN ANCESTRY AND MOVEMENT AND
AFRICAN POPULATION HAVE THE MOST
GENETIC ROLE.
AND THE LAST REASON WE SHOULD DO
THIS IS THROUGH H3 AFRICA HAS
ALLOWED TO IMPROVE THE GENETIC
ARCHITECTURE BY STUDYING 500
GENOME.
AND WE LOOKED AT GWAS VARIATION
AND I'LL SHOW HOW THIS WILL HAVE
AN IMPLICATION IN SICKLE CELL
DISEASE.
WE HAVE ALSO SUBJECT TO
VARIATION ALLOW THIS BUT I
BELIEVE THE GENOMICS ALLOW AND
I'LL ARGUE ONE IS MISSING AND
THE LOCI RESPONSIBLE FOR
EVALUATION EXPLAIN ONLY 20%
MAXIMUM VARIATION.
WE RERAN GWAS AND VALIDATED THE
REGION OF THE CHROMOSOME 6 BUT
FOUND A COUPLE LOCI.
ONE PRESENTED HERE AND I THINK
THESE ARE USED TO TRY TO MAKE
SURE WE HAVE THE SAME RESULT ON
DIFFERENT APPLICATIONS.
THIS IS ONE OF THE LOCI THAT
DESCRIBED THE GENES AND ONE THAT
MAKES A GOOD CANDIDATE BECAUSE
THE GENE IS STRONGLY REGULATED
IN THE RED BLOOD CELL AND OTHER
MODELS HAVE PRODUCTION OF RED
BLOOD CELL AND WE ALSO KNOW IT'S
ASSOCIATED WITH ERYTHROPOIESIS
AND WE LOOK AT THE SIMPLE MAP
LOOKING AT THE REGION OF THE
GENOME THAT IS VALID WITH THE
GWAS WE FOUND.
AND WE HAVE AN APPLICANTS AND
THERE'S AN INTERACTION BETWEEN
THE VARIANT AND THE GENES IN
THAT REGION AND SPECIFIC
ENHANCER AND ALLOWS US TO
IMPROVE THE CELL LINE AND MAYBE
ON ANIMAL MODEL.
A GROUP FOUND ONE GENE LAST YEAR
AND A DIFFERENT PATHWAY.
THAT'S DIFFERENT FROM WHAT WE
KNEW.
THAT MEANS THAT THESE TWO HAVE
SOME DISCOVERY TO GO.
AND I ARGUE THE AFRICAN
POPULATION IS INVOLVED IN THIS
AND THIS PATIENT HAD APPROACHES
THAT AFFECT THE QUALITY OF LIFE
AND SOME OF YOU HAVE SEEN THE
CONDITION AND THE CHALLENGES ARE
DIFFERENT IN DIFFERENT PARTS.
IN AFRICA WE LOOK AT TREATMENT
AND IN AMERICA THE LAST FEW
YEARS THE MORPHOLOGY HAS NOT
CHANGED AND AMERICA HAD
COMPLICATION SUBJECT TO
VARIATION AND THERE'S A
DYSFUNCTION ASSOCIATED WITH WHAT
SOLOMON SPOKE ABOUT AND THERE'S
STUDIES ON RESEARCH.
AND HIGH BLOOD PRESSURE IS
AFFECTED AND THERE'S STEMMIC
BLOOD PRESSURE IN SICKLE CELL
DISEASE ASSOCIATED WITH
COMPLICATION.
AND INVESTIGATED THOSE GENETIC
FACTORS ASSOCIATED WITH HIGH
BLOOD PRESSURE AND YOU CAN
PRESENT A MODEL THAT MAY PREDICT
COMPLICATION TO SOME OF THE
CARDIOVASCULAR COMPLICATION.
TO MY KNOWLEDGE THERE'S ONLY ONE
GWAS IN BLOOD PRESSURE IN SICKLE
CELL DISEASE.
AND WE LOOKED AT THE RESULT AND
WE HAVE AT LEAST TWO IN THE
SYSTOLIC BLOOD PRESSURE AND WE
LOOKED AT THE RELATION BETWEEN
THE BMI AND BLOOD PRESSURE AND
TO SEE IF WE CAN KEEP UP THE
SAME TYPE OF GENES.
WE SAW THE SAME ASSOCIATION.
IT IS POSSIBLE SOME OF THE
VARIANT WE FOUND ASSOCIATION
WITH DIABETES MILLITIS AND SOME
OF THE GWAS GENES WE FOUND SOME
WOULD BE CLOSE TO WHAT WE CAN
FIND AND WE LOOKED AT THE
VARIANT AND THE FACTORS.
AND WE LOOK AT DISEASE
PHYSIOLOGY AND WE STARTED WITH A
GROUP OF STUDIES AND THE SECOND
ONE ARE IN THEIR 40s, 50s AND
WHAT WE FOUND IS THAT THERE'S A
RARE VARIANT ASSOCIATED WITH
POTENTIAL PATHWAY PHYSIOLOGY AND
ONE INTERESTING PATHWAY WAS THE
ARGININE PATHWAY.
SUGGESTING THAT THAT PATHWAY MAY
BE LINKED WITH GENOMIC VARIATION
AND PRODUCTION OF AND ALLOW SOME
VARIATION AND BECAUSE OF MY
ANCESTRY MAY HAVE SICKLE CELL
DISEASE AND MAY HAVE BEEN IN THE
POPULATION AT LEAST 5,000 YEARS
AGO AND SUGGEST SICKLE CELL
DISEASE HAVE BEEN ASSOCIATED
WITH POTENTIALLY SPECIFIC
PRESSURE ON GENOME.
AND SOME OF THE VARIANTS HAVE
BEEN SELECTED BECAUSE OF THE
CONDITION AND THE SEVERITY OF
THE CONDITION OF THE SICKLE CELL
AND WE'RE NOW COMPARING THOSE
WITH AND WITHOUT SICKLE CELL
DISEASE AND IN THIS SLIDE AND
ASSOCIATED WITH GENOMES WE HAVE
NOW IN SICKLE CELL DISEASE AND
WE NEED TO LOOK AT THE
COMBINATION OF ALL THE VARIANTS
THAT HAVE BEEN SELECTED ON THE
AFRICAN CONTINENT AND THE
VARIATION.
WE KNOW THERE'S DYSFUNCTION.
AND WE STILL NEED TO INVESTIGATE
THE ACTUAL DATE OF THE
COMMUNICATION.
WHAT WILL HAPPEN BEYOND SICKLE
CELL DISEASE?
WE BELIEVE THE FOUNDATION OF THE
HUMAN GENOME PROJECT THAT ALLOW
US TO HAVE SOME BIAS AND WE
PROPOSE THE SEQUENCE IN
ASSOCIATION TO ADDRESS THE
MISSING LINK OF OUR HUMAN GENOME
AND WE'LL SEE THE PROJECT SOME
TIME LAST YEAR.
I WENT TO THANK ALL THE FUNDERS
AND THANK YOU SO MUCH.
>> WE'RE A LITTLE BIT OUT OF
TIME BUT THERE MAY BE QUESTIONS
OR COMMENTS ON THE CHAT AND Q&A.
YOU CAN RESPOND TO THEM.
ACCORDINGLY.
LET'S MOVE ON NEXT TO TO THE TOP
MED PROGRAM AND THE NEXT THREE
SPEAKERS WILL GIVE SNIPPETS OF
SICKLE CELL RELATED WORK USING
TOP MED DATA.
THE FIRST SPEAKER IS DR. MARILYN
TELLEN IN BIOLOGIC MEASURES AND
MULTI-OMICS AS PROGNOSTIC
FACTORS IN SICKLE CELL DISEASE.
>> I WAS TRYING TO GET TO MY
FIRST SLIDE.
>> SO WHAT I'M GOING TO DO TODAY
ALL THE TALKS TODAY HAVE BEEN
WONDERFUL INTRODUCTION TO WHAT I
HAVE TO SAY SO I'M GOING TO GO
THROUGH THE FIRST COUPLE SLIDES
REALLY FAST.
WE'VE HEARD ABOUT MEASUREMENTS
OF CELL BIOLOGY AND HEARD ABOUT
PROTEOMICS AND GENETICS.
WHAT I'M GOING TO TALK ABOUT IS
THE ACTUAL PROCESS OF PREDICTING
VARIABILITY IN SICKLE CELL
DISEASE AND SPECIFICALLY WHAT DO
WE WANT TO PREDICT AND WHY.
I WOULD ARGUE THAT WE WANT TO
PREDICT THINGS IN THE SHORT TERM
SUCH AS BOC FREQUENCY AND RISK
OF STROKE AND WE HAVE
THERAPEUTICS TO ADDRESS THOSE
THINGS AND WE WOULD LIKE TO
DIRECT THEM TO THE RIGHT PEOPLE.
ON THE LONG-TERM PROGNOSIS, WE
WORRY ABOUT END ORGAN DAMAGE
SUCH AS STROKE, KIDNEY DISEASE,
PULMONARY HYPERTENSION AND HOW
PATIENTS AGE AND SURVIVE OVER
TIME.
SO THE PURPOSE OF HAVING
PREDICTIVE MEASURES WOULD BE
BOTH PREVENTION AND TREATMENT.
I'M WAITING FOR THIS WE'VE
LOOKED AT PREDICTORS OF ACUTE
CHEST SYNDROME BUT THE ASSAY WAS
DIFFICULT TO WORK WITH.
I'LL MENTION THE ROLE OF
LEUKOCYTE ACTIVATION BECAUSE I
HAVE PRELIMINARY EVIDENCE AND
THEY'RE ACTIVATED IN SICKLE CELL
DISEASE.
WE KNOW THEY PARTICIPATE IN
HETEROCELLULAR FORMATION THAT
INVOLVES P SELECTIN.
UNFORTUNATELY WHEN A DRUG THAT
INHIBITED THAT AGGREGATE
FORMATION EXPERIMENTALLY WAS
GIVEN TO PEOPLE IT FAILED TO
INDUCE A SIGNIFICANTLY DECREASED
AMOUNT OF PAIN AND BASAL
OCCLUSION AND WE KNOW IN THE
PAST THAT SICKLE RED CELLS
INCLUDE NEUTROPHILS.
WHAT WE HAVEN'T KNOWN IS WHETHER
IMPROVEMENTS IN RED CELL HEALTH
LIKE THE THINGS YOU HEARD ABOUT
TODAY WITH SICKLING AND OTHER
SUCH THINGS ACTUALLY CHANGES THE
DEGREE TO WHICH SICKLE RED CELLS
AFFECT LEUKOCYTE ACTIVATION AND
IF SO IS THAT LINKED TO EVENTS
SUCH AS BASAL OCCLUSION.
AND THIS IS A SLIDE THAT I
PRESENTED AT THE GLOBAL SICKLE
CELL MEETING THIS SUMMER THAT
COMES FROM THE PHASE 1 TRIAL OF
A FORM OF THERAPEUTICS.
THEY WERE LOOKING AT SEVERAL
MARKERS OF INFLAMMATION.
ON THE RIGHT IS WHITE CELL COUNT
AND THE OTHER IS ANOTHER LEVEL
AND IN THE MIDDLE IS ONE OF THE
THINGS WIFE BEEN WORKING ON AND
THERE'S
-- WE'VE BEEN WORK ON AND WE SEE
LESS IN PATIENTS TREATED WITH
DRUG AND THERE'S SUGGESTIVE
EVIDENCE FROM THE PHASE 1 TRIAL
WHETHER THAT'S LINKED TO
DECREASED BASAL OCCLUSION.
AND JUST ANOTHER INTERESTING
FACT THAT COMES FROM A
DIFFERENCE STUDY THAT WE HAVE
BEEN DOING IS THAT NEUTROPHIL
ACTIVATION SEEMS TO BE STRONGLY
LINKED TO THE WHICH THEY EXPOSE
THES DRIVER FOR ACTIVATION OF
COAGULATION.
BUT IT ALSO SEEMS TO BE A DRIVER
OF NEUTROPHIL ACTIVATION.
SO LONG-TERM PROGNOSIS WHICH IS
WHAT I'LL SPEND THE REST OF THE
TIME ON, WE HAVE WONDERFUL
EVIDENCE ABOUT STROKE FROM MANY
PEOPLE'S WORK USING TRANS
CRANIAL DOPPLERS AND LOOK
LOOKING AT THE EFFECT OF
TRANSFUSIONS AND LEARNED A LOT
ABOUT NEPHROPATHY AND WE SHOWED
THE LINKAGE OF APOLL -- APOL 1
IN NEUROPATHY AND LOOKED AT A
RISK SCORE FOR PROGRESSION OF
SICKLE CELL NEPHROPATHY AND
SEVERAL PEOPLE HAVE SHOWN NICELY
AND IT'S REPRODUCED BY OTHERS
THAT ADHESION FACTORS SUCH AS
ICAM 1 ARE LINKED TO SUR VIEFRL
AS AND CLINICAL HISTORY WAS
LINKED TO LONG-TERM SURVIVAL BY
PLATT AND OUR SELVES AND OTHERS
HAVE SHOWN MULTI-ORGAN SEVERITY
SCORE HAS BEEN LINKED TO
SURVIVAL.
IN THINKING ABOUT WHAT HAPPENS
TO SICKLE CELL PATIENTS AS THEY
AGE AND GET OLDER, ON THE LEFT
YOU SEE SOME OF THE HIGH POINTS,
IF YOU WILL, IF SICKLE CELL
PATHOPHYSIOLOGY INCLUDING THE
CHRONIC INFLAMMATION AND
OXIDATIVE STRESS AND INCREASED
STEM CELL TURNOVER AND ON TOP OF
THAT WE HAVE THE GENETIC
VARIANTS.
SEVERAL OF WHICH YOU HEARD ABOUT
TODAY.
THEN WE HAVE ALL THE OTHER
PROCESSES DURING AGING, DNA
MITOCHONDRIAL DNA COPY NUMBER
NAH NATURALLY DECREASES AS
THERE'S ACQUIRED DNA DAMAGE.
WE SEE CLONAL HEMATOPOIESIS IN
EVERYBODY WITH OR WITHOUT SICKLE
CELL DISEASE AS THEY AGE.
WE SEE INCREASING CHIP.
YOU GET TELOMERE SHORTENING AND
AGE-RELATED DNA METHYLATION
CHANGES AND THIS HAPPENS IN
EVERYBODY NATURALLY WHETHER THEY
HAVE SICKLE CELL DISEASE OR NOT.
THE QUESTION IS DO THEY HAPPEN
DIFFERENTLY AND IN AN
ACCELERATED WAY AND IN WHAT WAY,
IF ANY, DO THEY PARTICULARLY
CONTRIBUTE TO AGING AND SURVIVAL
IN SICKLE CELL DISEASE.
WHAT WE'RE TRYING TO DO IS LOOK
AT MEASURES OF PHYSIOLOGIC
DYSFUNCTION AND PROTEOMIC
MEASURE AND ORGAN INJURY AND
MEASUREMENTS OF FRAILTY IN ORDER
TO UNDERSTAND EARLY MORTALITY
VERSUS MORE SUCCESSFUL AGING.
AND THIS IS JUST A RECAP OF WHAT
I'VE SAID WHICH I'M GOING TO GO
OVER FAST IN THE INTEREST OF
TIME.
SO OUR GOAL IS TO IDENTIFY THE
MULTIPLE FACTORS CONTRIBUTING TO
ADVERSE OUTCOMES AND TO DEVELOP
A ROBUST ALGORITHM USING THE
FACTORS IN APPROPRIATE FASHION
TO PREDICT SURVIVAL AND FRAILTY
BASED ON CLINICAL AND
METABOLOMIC AND PROTEOMIC AND
GENETIC FACTORS.
TO DO THIS WE'RE USING THE ADULT
SICKLE CELL COHORTS YOU SEE
HERE.
TOGETHER GIVE US ABOUT ALMOST
4,000 PATIENTS.
THESE ARE ALL ADULT PATIENTS AND
THEY HAVE A VARIETY OF
PHENOTYPIC DATA AVAILABLE AS
WELL AS WHOLE GENOME
SECOND-CHA
SECOND-CHANCING AND SOMETIMES
PROTEOMICS AND SOMETIMES OTHER
MEASUREMENTS.
NOW, ONE OF THE THINGS, DUKE HAS
BEEN PIONEERING UNDERSTANDING
AGING AND FRAILTY IN SICKLE CELL
PATIENTS.
AND THE LITERATURE ON FRAILTY
UNTIL FAIRLY RECENTLY I THINK
HAS NOT BEEN ALL THAT RELEVANT
TO SICKLE CELL PATIENTS PERHAPS
BUT IT'S WELL SHOWN THAT
MEASUREMENTS OF FRAILTY HAVE
PREDICTIVE VALUES IN MANY
POPULATIONS WITH AND WITHOUT
CHRONIC DISEASES.
SO WE'VE BEEN TRYING TO IDENTIFY
OR DESIGN A CLINICAL AND FRAILTY
BASED INDEX THAT IS A BETTER
PREDICTOR OF SURVIVAL THAN OUR
PREVIOUSLY USED MULTI-ORGAN
SEVERITY SCORE.
WE DID THAT AND LOOKED AT
FACTORS IN THE FRAILTY INDEX
CONSISTENT OF 24 LABORATORY AND
PHYSICAL EXAM BASED FACTORS AND
LOOKED AT THE PREDICTED
SURVIVAL.
ON THE LEFT IS THE ORGAN
SEVERITY SCORE WE USED AND
PUBLISHED PREVIOUSLY AND ON THE
RIGHT IS THE SURVIVAL BY FRAILTY
INDEX AND IT SEEMS A BIT MORE
POWERFUL AND THERE'S OUR ATTEMPT
AT THE FRAILTY INDEX AND WE'RE
WORKING TO OPTIMIZE IT TO
INCLUDE ADDITIONAL NON-SICKLE
CELL RELATED PATHOPHYSIOLOGIES
EASILY AVAILABLE FOR MOST
ELECTRONIC HEALTH RECORDS.
THE POINT OF THIS BEING THAT ALL
ALL THE ITEMS IN THE FRAILTY
INDEX ARE THINGS THAT YOU CAN
EXTRACT FROM MEDICAL RECORDS.
YOU DON'T HAVE TO DO ADDITIONAL
TESTING.
NOW, IN ADDITION, WE ARE LOOKING
AT OTHER MEASUREMENTS OF AGING,
TELOMERE LENGTH IS ONE OF THE
ESTABLISHED MARKERS OF AGING BUT
IN SICKLE CELL DISEASE THOUGH
THERE HAVE BEEN A FEW STUDIES
THEY'RE SOMEWHAT CONTRADICTORY
BECAUSE HYPOXY UREA AFFECTED AND
RECENTLY TOP MED HAS IDENTIFIED
36 LOCI ASSOCIATED WITH TELOMERE
LENGTH 20 OF WHICH WERE NOVEL
COMPARED TO PREVIOUS LITERATURE.
MITOCHONDRIAL DNA COPY NUMBER
VARIES AMONG INDIVIDUALS AND
INFLUENCED BY GENETICS AND
PHYSIO LOGIC PROCESSES WITH
LEUKOCYTE CONTENT ESPECIALLY
REFLECTING OXIDANT-INDUCED CELL
DAMAGE WHICH IS QUITE RELEVANT
TO SICKLE CELL DISEASE.
MITOCHONDRIAL DYSFUNCTION IS A
MAJOR HALLMARK OF AGING AS WELL
AS SICKLE CELL DISEASE AND IT'S
BEEN STUDIED IN OTHER DISEASES
AND CONDITIONS FOR ASSOCIATION
WITH CLINICAL OUTCOMES SUCH AS
HYPERTENSION, CARDIOVASCULAR
DISEASE AND DIABETES AND HAS
BEEN IN DEPDEPENDENT WITH
CARDIOVASCULAR DISEASE IN THREE
PROSPECTIVE STUDIES WE
HYPOTHESIZE THE MITOCHONDRIAL
DNA WILL PROVIDE INFORMATION TO
IDENTIFY INDIVIDUALS PRONE TO
INFLAMMATORY AND VASCULAR PATHIC
AND ORGAN DAMAGE AMONG PATIENTS
WITH SICKLE CELL DISEASE.
LOOKING AT TELOMERE LENGTH AND
MITOCHONDRIAL DNA COPY NUMBER WE
HAVE THUS FAR ONLY USED OUR ONLY
DATA SET WHICH IS PROBABLY JUST
SHY OF 600 PATIENTS AND WE'VE
LOOKED AT FOUR ASSOCIATIONS OF
TELOMERE LENGTH AND
MITOCHONDRIAL DNA COPY NUMBER.
WE SEE SOME INTERESTING
ASSOCIATIONS SUCH AS THE COPY
NUMBER ON HYDROXYUREA USE
PERHAPS THE TELOMERE LENGTH AND
BRONCO DIE -- DILATOR USE AND
LOOK AT HEMOLYSIS LIKE BILIRUBIN
AND HOPE TO EXTEND THESE TO THE
OTHER TOP MED DATA SETS I SHOWED
PREVIOUSLY.
CLONAL HEMATOPOIESIS IS NOT ONLY
A MARKER FOR FUTURE
HEMATOPOIETIC MALIGNANCIES AND
HAS BEEN SHOWN TO BE A MARKER
FOR OTHER DISEASES SUCH AS FOR
LIVER AND HEART.
AND THEY'RE AMONG THE SLIGHTLY
LESS THAN 98,000 PARTICIPANTS OF
DIVERSE ANCESTRIES.
AND THERE'S BEEN TWO RECENT
STUDIES AND THE ONE COMING FROM
TOP NED WHICH DID NOT SHOW A
SIGNIFICANT INCREASED RISK OF
CHIP AND THE ONE COMING FROM THE
GROUP HEADED WHICH SHOWED AN AND
INTERESTINGLY IN TOP MED HAS
ALSO USED MENDEL YAN
ASSOCIATION AND I WANT TO GET TO
THE EPIGENETIC EVALUATION WHICH
WE ALSO HAVE UNDERWAY WITH OUR
TOP MED GROUP.
AGAIN, PATIENTS WITH SICKLE CELL
DISEASE ARE 20 TO 30 YEARS OLDER
THAN THEIR CHRONOLOGIC AGE
COMPARED TO OTHER PATIENTS.
SO WE'RE GOING TO LOOK AT
PROTEOMICS AND WE'VE DONE THAT
SO SOME EXTENT WITH NEPHROPATHY.
AND THIS IS RELATED TO OUR
SURVIVAL IN OUR PRELIMINARY
PROTEOMICS AND IN OUR
PRELIMINARY METABOLOMICS.
THIS IS PUBLISHED DATA SO I'M
JUST GOING TO REMIND YOU THAT WE
HAVE BEEN WORKING ON RISK SCORES
AND THIS IS TO ILLUSTRATE THE
KIND OF THING WE HOPED TO DO IS
TO DEVELOP A MUCH MORE COMPLETE
RISK SCORE FOR THINGS LIKE
NEPHROPATHY AND SURVIVAL.
I THINK WITH THE MULTIPLE TOP
MED DATA SETS WE SHOULD BE ABLE
TO IDENTIFY A SET OF PREDICTORS
AMONG ALL THE OMICS MEASURES
THAT ARE ROBUST AND WILL BE
USEFUL.
WE'LL USE A NUMBER OF DIFFERENT
METHODS.
I WON'T GET INTO THAT FOR THE
LACK OF TIME BUT WE WILL
INCORPORATE CLINICAL EPIGENETIC
AGE AND TELOMERE AGE AND
MITOCHONDRIAL DNA RISK FACTORS
AS WELL AS MEASUREMENTS OF
FRAILTY AND THEN IN THE SECOND
SET OF MOLTS WE'LL INCLUDE THE
PROTEOMICS AND METABOLOMICS
DATA.
A COMPREHENSIVE STUDY OF THESE
RISK FACTORS IS LOOKING IN
SICKLE CELL DISEASE BUT HOLDS
THE POTENTIAL FOR REALLY
PRODUCING THE ABILITY TO RISK
STRATIFY AND TO MAKE OUR
CLINICAL STUDIES OF
INTERVENTIONS BETTER BY
IDENTIFYING TRULY PATIENTS AT
RISK FOR A PARTICULAR OUTCOME
AND ALSO POSSIBLY TO ELUCIDATE
NEW MECHANISMS OF PATH YO --
PATH YOO PHYSIOL
PATHOPHYSIOLOGY AND HOPE TO
TARGET NEW PATIENTS FOR THE
TRIAL AND WILL HIGHLIGHT SOME OF
THE PEOPLE WHO PARTICIPATED IN
THE STUDIES AT DUKE AND MY PA
PARTNER AND HAVE BUILT THIS
PROGRAM WITH OUR SUPERB
STATISTICIAN AND JJ STRAUSS WHO
RUNS OUR ADULT SICKLE CELL
PROGRAM AND OTHER PEOPLE AT DUKE
AND OUR COLLABORATORS AT NORTH
CAROLINA AND EMORY AND THE
UNIVERSITY OF MONTREAL AND THE
OTHER TOP MED SICKLE CELL
COHORTS AND THEIR P.I.s AND ALL
THEIR STAFF WHO ENROLLED SO MANY
PATIENTS IN THE COHORTS.
THE FUNDS HAVE LARGELY COME AS
SHOWN IN THE BOTTOM OF THE
SLIDE.
I'LL END THERE.
>> THANK YOU, MARILYN.
I THINK WE'LL MOVE ON TO OUR
NEXT TALK.
THERE MAY BE COMMENTS AND
QUESTIONS FOR YOU IN THE CHAT
WHICH YOU CAN RESPOND TO.
NEXT SPEAKER IS GOING TO BE
DR. REINER PROTEOMIC ANALYSIS OF
SICKLE CELL TRAIT IN TOP MED.
>> THIS THANK YOU FOR THE
OPPORTUNITY TO PRESENT IN
PRELIMINARY RESULT IN PROTEOMIC
ANALYSIS IN THE SICKLE CELL
TRAIT.
WHILE SICKLE CELL DISEASE IS
CLEARLY AN IMPORTANT HEREDITARY
BLOOD DISEASE AND OBVIOUSLY THE
FOCUS OF THIS MEETING THE COPY
OF THE SICKLE CELL MUTATION AS
SHOWN ON THE BOTTOM RIGHT IS
MORE COMMON IN THE
U.S. AFFECTING 8% OF THE AFRICAN
AMERICAN POPULATION.
WHILE SICKLE CELL TRAIT HAS BEEN
CONSIDERED A RELATIVELY BENIGN
CONDITION WITH NO CLINICAL
SEQUELAE, MORE RECENTLY, HAVE
ASSOCIATED IT WITH INCREASE RISK
OF KIDNEY AND THROMBOLIC
DISEASE.
THE ORIGINAL OBSERVATION
ASSOCIATED WITH KIDNEY DISEASE
WAS MADE IN 2014 WAS BASED ON A
META-ANALYSIS OF FIVE
POPULATION-BASED NHLBI COHORT
STUDIES SHOWN HERE, CARDIA MESA
AND OTHERS WHERE SICKLE CELL
TRAIT WAS ASSOCIATED WITH
INCREASED EGFR AND TWOFOLD
INCREASE OF KIDNEY DISEASE
ACROSS A TOTAL OF ABOUT 16,000
AFRICAN AMERICAN PARTICIPANTS.
AND THE ASSOCIATION OF KIDNEY
DYSFUNCTION IS CONSISTENT WITH
DATA FROM RENAL
MICROANGIOGRAPHIC STUDIES DATING
BACK TO THE 1970s SHOWING
DESTRUCTION OF THE RENAL MEDULLA
IN SICKLE TRAIT SHOWN IN THE
MIDDLE PANEL INTERMEDIATE
BETWEEN HEALTHY INDIVIDUAL ON
THE LEFT AND SICKLE CELL DISEASE
ON THE RIGHT.
AND THE HYPOXIA ACIDOSIS AND
DERYE DRAGS AND SLOW BLOOD FLOW
PROMOTE HEMOGLOBIN POLY
POLYMERIZATION AND INCREASED
RISK OF KIDNEY DISEASAGE
COMPLICATIONS.
THROUGH THE NHLBI SEQUENCING
PROGRAM AND THE HEMATOLOGY AND
HEMOST
HEMOSTAIFS
-- HEMOSTAVES
HEMOSTASIS WORKING GROUP WHO
PARTICIPATED IN THE CHRONIC
KIDNEY DISEASE META-ANALYSIS WE
AND THE WORKING GROUP MEMBERS
HAVE STUDIED THE TRAIT IN THE
AFRICAN AMERICAN POPULATION.
SO THROUGH THE TOP MED
HEMATOLOGY WORKING GROUP WE HAVE
RECENTLY SHOWN IN ADDITION TO
BEING A RISK FACTOR FOR KIDNEY
DISEASE AND VENUS THROMBOSIS
SICKLE CELL DISEASE TRAIT IS
ASSOCIATED WITH PHENOTYPES NOT
ONLY LOWER EGFR AND LOWER
HEMOGLOBIN LEVELS AND MCB AND
HIGHER HEMOGLOBIN A1C LEVELS AND
LOWER CIRCULATING LYMPHOCYTE
COUNTS.
HOWEVER, STILL RELATIVELY LITTLE
IS KNOWN BY THE MECHANISMS
UNDERLYING THE PHENOTYPIC
ASSOCIATIONS.
WHILE LOTS OF PROGRESS HAS BEEN
MADE OVER THE YEARS IN
UNDERSTANDING HOW SICKLE
HEMOGLOBIN POLYMERIZATION AND
LEUKOCYTE ACTIVATION AND ALL
THINGS WE HAVE HEARD MUCH ABOUT
TODAY LEAD TO INCREASED
VISCOSITY AND VASO INCLUSION AND
CONTRIBUTE TO THE CLINICAL
SEQUELAE OF SICKLE CELL DISEASE
THE MECHANISMS UNDERLYING THE
CONSEQUENCES OF SICKLE CELL
TRAIT ARE NOT AS WELL AS STUDIED
AND THEREFORE LESS UNDERSTOOD.
SO WITH THIS BACKGROUND OF THE
POTENTIAL PUBLIC HEALTH
IMPORTANCE OF SICKLE TRAIT IN
MIND, TOGETHER WITH THE FOCUS OF
THE FIRST PHASE OF TOP MED WHOLE
GENOME SEQUENCING ON RACIAL
DIVERSITY INCLUDING A SIZABLE
NUMBER OF AFRICAN AMERICAN
PARTICIPANTS AS SHOWN ON THE
LEFT IN ORANGE AND NOW THE
AVAILABILITY DURING THE CURRENT
PHASE OF TOP MED SHOWN ON THE
RIGHT
>>
>> SCORERY, IS THIS THE RIGHT
SLIDE?
>> THE TOP MED SLIDE?
>> YEAH.
AND
>> SO SPECIFICALLY OUR PROJECT
INVOLVES ABOUT 2,000 FRONTRUNNER
S AND WE'RE CURRENTLY GENERATING
METHYLIZATION AND THERE'S TWO
TIME POINTS 15 YEARS APART.
THE SAMPLES FOR MULTI-OMICS WERE
SELECTED BASED ON THE SICKLE
CELL GENOTYPE STATUS AT THE
RS334 SNIP AND THE OVER ALL
PROJECT CAN BE DIVIDED INTO A
COUPLE SPECIFIC AIMS AS
SUMMARIZED HERE.
THERE'S THE PROTE OMIC CARRIERS
AND NON-CARRIERS USING THE
ANTIBODY-BASED PLATFORM WHICH
CONTAINS ABOUT 1500 PROTEINS.
THIS SLIDE SHOWS THE WOMEN'S
HEALTH INITIATIVE OR WHI WHICH
IS A LARGE MULTI-CENTER
PROSPECTIVE STUDY OF
POST-MENOPAUSAL WOMEN IN THE
U.S. WHERE PARTICIPANTS WERE
RECRUITED FROM 40 CLINICAL
CENTERS AND THE OVER ALL SAMPLE
INCLUDES ABOUT 15% AFRICAN
AMERICAN WOMEN RECRUITED FROM
ABOUT EIGHT MINORITY CENTERS.
THIS TABLE SUMMARIZES THE
BASELINE CHARACTERISTICS OF THE
600 SICKLE SAFE CARRIERS AND 600
AGE-MATCHED CONTROLS.
YOU CAN SEE ASPECT ED --
EXPECTED THE HAD GFRs AND HIGHER
PREVALENCE OF DIABETES.
HERE'S A TABLE COMPARING
AGE-ADJUSTED PROTEIN LEVELS
BETWEEN THE 600 SICKLE CELL
TRAIT AND 600 NON-CARRIERS.
SO THE P VALUE THRESHOLD OF 1500
PROTEINS THERE'S A TOTAL OF 35
PROTEINS SIGNIFICANTLY
ASSOCIATED WITH SICKLE TRAIT
STATUS.
AND WE CAN SEE THE TOP TWO
PROTEINS ARE THE CHEMO KINES AND
THE INJURY MOLECULE 1 WHICH
ALONG WITH OTHER PROTEINS
HIGHLIGHTED IN GREEN SUCH AS UR
AND MCP1 HAVE BEEN PREVIOUSLY
ASSOCIATED WITH BOTH
INFLAMMATORY AND KIDNEY DISEASES
MORE GENERALLY.
HIGHLIGHTS IN RED ARE OTHER
PROTEINS RELATED TO RED CELL
MORPH O
MORPHO
MORPHOLOGY AND SEVERAL OF THE
TOP PROTEINS DID REMAIN
SIGNIFICANTLY ASSOCIATED WITH
SICKLE CELL TRAIT EVEN AFTER
ADJUSTING FOR BASELINE EGFR OR
KIDNEY FUNCTION.
NEXT WE CREATED A PROTEIN RISK
SCORE FROM THE TOP SICKLE TRADE
ASSOCIATED PROTEINS AND THEN
TESTED WHETHER THE SICKLE TRAIT
PROTEIN RISK SCORE MEASURED AT
BASELINE PREDICTS FUTURE KIDNEY
DISEASE OUTCOMES ASSESSED 15
YEARS LATER IN WHI.
AND AT LEAST THERE'S SOME
PRELIMINARY EVIDENCE TO SUGGEST
THAT THIS SICKLE TRAIT PROTEIN
RISK SCORE WHEN ADJUSTED FOR
BASELINE AGE AND EGFR PREDICTED
THE DECLINE IN KIDNEY FUNCTION
AS WELL AS INCIDENT END STAGE
KIDNEY DISEASE.
SO IN SUMMARY WE SHOW SOME
PRELIMINARY ANALYSIS IDENTIFYING
A NUMBER OF PLASMA PROTEINS
ASSOCIATED WITH SICKLE TRAIT.
SOME OF WHICH MAY ULTIMATELY BE
INFORMATIVE FOR SICKLE
ASSOCIATED NEPHROPATHY AND
CARRIERS AS WELL AS PATIENTS
WITH SICKLE CELL DISEASE.
THE GENERATION OF ADDITIONAL
MULTI-OMICS DATA AND
METABOLOMICS AND METHYLATION AND
IN THE CONTROL SAMPLE ULTIMATELY
MADE ALLOW FURTHER INTEGRATIVE
ANALYSIS INTO INFORM MECHANISMS
UNDERLYING BOTH SICKLE TRAIT AND
SICKLE DISEASE AS RELATIONSHIP
TO OTHER CLINIC TRAITS AND
OUTCOMES.
AND LOOKING AT THE TOP MED
PROGRAM IN HEMATOLOGY AND SICKLE
WORKING GROUPS AND NHLBI FOR
MAKING THIS PROJECT POSSIBLE.
THANK YOU.
>> THINK THE DATA WE PRESENT
HERE IS FAIRLY PRELIMINARY AND
STILL THE NEXT STEP IS REALLY TO
TEST ITS ROBUSTNESS AND
REPLICATION AND INDEPENDENT
SAMPLES.
PERSONALLY, I'M NOT AWARE OF
ASSUMING SAYING SOMETHING LIKE
FRACTOKINE IS MECHANISTICALLY
IMPORTANT OR I'M NOT AWARE OF
DRU
DRUGS.
>> THANK YOU FOR A GREAT TALK.
>> LET'S GROW -- GO TO OUR LAST
TALK OF THE DAY FOR ERIC EARLY
AND LOOKING AT GENOMIC-WIDE
ASSOCIATION OF EARLY ISCHEMIC
STROKE IN BRAZIL SICKLE CELL
DISEASE CONFIRMS.
>> THANK YOU FOR BEING HERE.
BEING THE LAST SPEAKER I KNOW
EVERYONE'S TIRED.
I'M A GENETICISTS AND I COME
FROM A PEDIATRIC ONCOLOGY AND
WHOLE GENOME SEQUENCING
BACKGR
BACKGROUND AND WE'RE A
NON-PROFIT RESEARCH INSTITUTE
AND WE WORKED WITH CHAPEL HILL
AND OTHER UNIVERSITIES.
AND STROKE BEING HIGHER AT UNDER
AGE 14 WITH HEMORRHAGIC BEING
MORE COMMON IN THEIR 20s AND
THERE'S A REVIEW AND GO TO THE
COHORT AND IN BLUE IS THE STROKE
FOR SICKLE CELL ANEMIA.
AND THE SICKLE HAS A HUGE
GENOTYPE IS IMPORTANT AND HBSS
HEADLINES HAVE THE HIGHEST
FACTORS AND THE BIGGEST FACTORS
ARE LISTED AND THE OTHERS BEYOND
THAT ARE MIXED.
THERE'S BEEN A LOT OF WORK IN
STUDIES FOR DECADES BUT THE GWAS
INCLUDE REALLY ONLY ONE AND WE
LOOKED AT THE GENES BUT THEY
HAVEN'T BEEN REPLICATED SINCE.
AND IT DID NOT REPLICATE THIS WE
THINK THERE'S A CLEAR KNOWLEDGE
GAP HERE.
AND THIS WAS ONE OF THE RESEARCH
PRIORITIES FOR THE RECIPIENT IN
EPIDEMIOLOGY STUDY PHASE 3
PROGRAM AND THERE'S A NATIONAL
COLLABORATION WITH RESEARCH
CENTERS IN THE U.S. AND SIX
CENTERS AND AT UNIVERSITIES IN
BRAZIL AND THESE BLOOD CENTERS
ARE THE CLINICS PARTICIPANTS
THAT CONTINUE THEIR CARE.
WE WERE ALSO LUCKY TO GET WHOLE
GENOME SEQUENCING BY TOP MED.
THIS INCLUDED ACROSS THE WHOLE
GENOME.
WE USED 30XA.
AND MINOR ALLELE FREQUENCIES AND
LEAVING ABOUT 18 MILLION SNPs
AND INDELS AND PRINCIPAL
COMPONENT WERE CALCULATED FOR
THE GENETIC BACKGROUND OF
INDIVIDUALS AND OF THE ROUGHLY
3,000 ENROLLED THE 500 WERE NOT
SEQUENCED.
FOR VARIOUS TECHNOLOGY REASONS
THE DATA HAD PC ISSUES AND TOOLS
WERE EXCLUDED AND THEN WE DID
FOCUS ON THE HOMO ZYGOTES AND
THIS IS THE FIRST ROUND OF
STUDIES WE WANTED THE STRONGEST
SIGNAL BECAUSE 1,000 INDIVIDUALS
IS A LOT IN THE CONTEXT OF THE
FIELD BUT IN THE CONTEXT OF GWAS
IT'S FAIRLY SMALL.
WE WANTED TO MAKE SURE THE
DISEASE STRENGTH WAS STRONG AND
SO WE DID FOCUS ON HOMO ZYGOTES.
THE FINAL BOX HERE WE DID ALSO
EXCLUDE 230 INDIVIDUALS WHO
EXPERIENCED NO STROKE AROUND
REPORTED NO STROKE.
AND EITHER UNDERGOING PRODUCT
TRANSFUSION THERAPIES OR HAD A
NORMAL TRANS CRANIAL DOPPLER AND
OUR REASONING WAS TO TRY TO MAKE
SURE THAT WE HAD A STRONG
GENETIC SIGNAL AND IN THE
CONTROL CASE INDIVIDUALS HAVE
HIGHER RISK OF STROKE AND
ULTIMATELY WE WERE LEFT WITH A
STUDY COHORT OF 1,300
PARTICIPANTS.
AND THIS WAS WELL REPRESENTED
ACROSS THE CENTERS ON THE RIGHT
YOU SEE THE BREAKDOWNS AND
NUMBER OF INDIVIDUALS WITH
STROKE ON THE Y AXIS.
FOR THIS REASON WE WANTED TO
ADDRESS THE COMPONENT AND DIDN'T
WANT TO EXCLUDE PEOPLE.
WE ENDED UP IMPLEMENTING A COX
PROPORTIONAL HAZARDS MODEL AND
IT MEASURES DIFFERENCES SO IT'S
COMMON THE RESPONSE IS TIME FOR
STROKE FOR CENSORING ENROLLMENT
OR LAST VISIT AND LIKE I
MENTIONED THE TOP 10 PRINCIPAL
COMPONENTS OF THE GENETIC
ANCESTRY UNRELATED TO THE
DISEASE AND STROKE WERE PART OF
THE CONTROL GROUP.
THIS IS A VERY MIXED POPULATION.
THE Y AXIS AND THE LOWER THE P
VALUE THE HIGHER YOU ARE ON THE
Y AXIS.
THE DOTTED LINE REPRESENTED
GENOME WIDE SIGNIFICANCE AND
GENES ARE ANNOTATED HERE BY THE
GENES CLOSEST TO THE SNIP WITH
THE BEST OR LOWEST P VALUE THEN
I COLOR CODED THEM BASED ON
LITERATURE RESEARCH OF PREVIOUS
GENETIC STUDIES AND TURNED OUT
THREE OF THESE CDK18 HAD BEEN
LINKED TO STROKE BEFORE AND THE
GENES HAVE BEEN LINKED TO OTHER
CARDIOVASCULAR TRAITS I'LL SHOW
ON THE NEXT SLIDE.
WE FOUND A COUPLE THAT HAD NO
PREVIOUS ASSOCIATION WITH
STROKE.
AND THE GENOMIC CONTROL SUGGESTS
NO INFLATION OF P VALUE AND
THEY'RE SIGNAL NOT JUST NOISE
FROM OUR MODELLING.
HERE I'M SLOWING THE GENES AND
RELATIVE EFFECTS AND THEY HAVE A
RATIO OF BASED RISK AND ERROR
AND THEN THE LITERATURE.
AND THERE'S PEDIATRIC AND EARLY
ONSET.
AND THE JAPANESE COHORT IS
WRITING A PAPER WITH A
U.S. COHORT AND THESE ARE
NON-SICKLE COHORTS.
THESE ARE EARLY ONSET NON-SICKLE
COHORTS.
NONE OF THE GENES LISTED HERE
HAVE BEEN LINKED TO SICKLE
SPECIFICALLY.
HERE YOU'RE SEEING A ZOOM IN OF
THE LOCUS.
UP TOP IS THE MODIFICATION WITH
THE COLOR ADDED TO ENHANCE THE
SNPs IN LINKAGE.
AND YOU CAN ADD LOW RISK
INDIVIDUALS AND RED REPRESENTS
HOMOZYGOUS INDIVIDUALS.
AND THERE'S PEDIATRIC SICKLE
ISCHEMIC STROKE AND THIS IS
SLIGHTLY MORE RARE TOWARDS THE
1% OBSERVED FREQUENCY.
SINCE WE HAVE 14 INDEPENDENT
RISK LOCI THERE WEREN'T A LOT OF
INCREASED RISK BUT THE GROUPING
I'M PRESENTING HERE SHOWS
INDIVIDUALS WITH ZERO RISK
ALLELES.
ONE, TWO, THREE, FOUR OR MORE.
AND TAKING A STEP BACK TO A MORE
PHYSIO LOGIC AND PHYSIOLOGICAL
SYSTEMS, AN ENRICHMENT TEST CAN
SHOW CANDIDATES BASED ON VARIOUS
LINES OF EVIDENCE AND THE
OVERREPRESENTATION OF THE GENE
IN PARTICULAR GENE SETS MAY
SUGGEST THAT VARIANTS IN THOSE
GENES OR NEAR THOSE GENES ARE
DISRUPTING THESE PATHWAYS.
AND YOU CAN HAVE THEM ENRICHED
IN THE PATHWAY AND THERE'S A
MEMBRANE PARTICULARLY INVOLVED
OUTREACH OF ENRICHMENT AND
HEMOGLOBIN AND THE BLOOD
PRESSURE.
AND YOU CAN SELECT THIS AS
APPROPRIATE AND WE EXPECT TO SEE
EVIDENCE OF VARIANTS ASSOCIATED
WITH STROKE ASSOCIATED WITH
ASSOCIATION WITH GENES
ASSOCIATED WITH STROKE AND
SIMILAR WE DO AND WE SEE
ENRICHMENT OF THE 18 CANDIDATE
GENES.
I LOOKED FOR OVER REPRESENTATION
OF THOSE GENES WITHIN GENE SETS
AFFILIATED WITH GENE EXPRESSION
IN THE TISSUES.
THAT MEANS IN THIS CASE IN THE
HYPOTHALAMUS IN THE FAR LEFT I'M
SEEING SIGNIFICANT FALSE
DISCOVERY RATE AND MULTIPLE
HYPOTHESIS AND OVER
REPRESENTATION OF THE 18
CANDIDATE GENES AND GENES THAT
ARE DIFFERENTIALLY EXPRESSED IN
THE HYPOTHALAMUS SUGGESTING
THESE TISSUES ARE WHAT IS
MEDIATING THE PATHOPHYSIOLOGY.
WE ALSO SEE STRONG SIGNAL IN THE
ARTERIES AND TIBIAL AND I'M NOT
SURE WHAT TO THINK ABOUT THAT.
AND IN SUMMARY WE DISCOVERED
EARLY ONSET STROKE GENES
PREVIOUSLY KNOWN TO BE RELATED
TO ISCHEMIC STROKE RISK.
WE REPLICATED THEM IN THIS
BRAZIL COHORT AS WELL
DISCOVERING LOCI AND THE
ENRICHMENT RESULTS SHOWED
EXPRESSION IN ARTERIES AND
THALAMUS AND AS USUAL WITH GWAS
THE NEXT STEP IS VALIDATION AND
CALCULATING POLY GENIC RISK
SCORES AND VALIDATING NEW
COHORTS ESPECIALLY IN AFRICAN
COHORT.
I'M ALSO PERSONALLY INTERESTED
IN THE ROLE OF NON-ENCODING
VARIANT WITH METHYLATION AND
GENE EXPRESSION CHANGES AND
ALWAYS INTERESTED IN
COLLABORATION ON THAT AS WELL AS
METABOLOMICS.
NONE OF THIS WORK WOULD HAVE
BEEN POSSIBLE WITHOUT THE
INCREDIBLE COLLABORATORS.
AND APOLOGIES I DON'T SPEAK
PORTUGUESE ON THE NAMES.
>> THANK YOU FOR THE LAST TALK.
THANKS TO THE AUDIENCE TOO AND
THERE'S A COUPLE QUESTIONS IN
THE COMMENT SECTION.
CAN YOU SEE THEM OR DO YOU WANT
ME TO READ?
>> IT'S IMPORTANT TO TRACK.
IT HAS EFFECTS.
SO STROKE WAS EXTRACTED FROM THE
MEDICAL RECORDS.
I'M REALLY INTERESTED IN MRI.
I WAS RECENTLY CHATTING WITH A
COLLEGIATE DUKE ABOUT MACHINE
LEARNING OF MRIs PREDICTING THE
SYSTEMIC BLOOD FLOW CHANGES IN
CERTAIN DISEASES AROUND IN THIS
CASE I THINK MRI WOULD BE A REAL
INTERESTING RESPONSE TO STUDY.
>> THERE'S A QUESTION FROM
DR. GUP TA.
WHAT ARE YOUR THOUGHTS ABOUT
DOPAMINE-TARGETED GENES.
THOSE CAN BE RELEVANT TO
FUNCTION.
>> I AM NOT AN EXPERT.
I WILL RESPECTFULLY ASK OTHERS
TO INTERVENE AND I HAVEN'T SEEN
THIS ASSOCIATION UNLESS I'M
MISSING OR IT'S POPPING OUT TO
OTHERS ON THE CALL.
THAT'S A GOOD THING TO FOLLOW-UP
ON.
THANK YOU.
>> OKAY.
I DON'T SEE ANY OTHER ADDITIONAL
COMME
COMMENTS.
THANK YOU VERY MUCH AGAIN FOR
THE WONDERFUL TALK AND SESSION
AND THANK YOU, AUDIENCE, FOR
HANGING IN THERE FOR THE LAST
TALK.
WE HAVE TOMORROW ANOTHER FULL
DAY FOR TALKS THAT START AT 9:00
TOMORROW MORNING IN SYMPOSIUM 5.
THE THEME FOR TOMORROW WILL BE
PAIN AND SICKLE CELL WHICH IS A
MAJOR ASPECT OF SICKLE DISEASE
AND YOU'LL BE HAPPY TO HEAR
TALKS TOMORROW AND IT STARTS AT
10:00 TOMORROW MORNING AND
HOPEFULLY WE'LL SEE YOU TOMORROW
AT 9:00.
I DON'T HAVE ANYTHING ELSE.
ALEX, DO YOU HAVE LOGISTICS TO
TALK ABOUT FOR TOMORROW?
>> NOT AT THIS TIME BUT A
REMINDER TO USE YOUR DAILY LOG
IN AND THE SPEAKERS PLEASE
REMEMBER TO LOG IN EARLY
TOMORROW MORNING TO JOIN US AND
THANK YOU AGAIN AND WE'LL SEE
YOU TOMORROW.
>> THANKS, ALEX.
THANK YOU AGAIN FOR ALL THE
SPEAKERS FOR TODAY AND LOOK
FORWARD TO SEEING YOU TOMORROW
FOR ANOTHER FULL DAY OF
WONDERFUL TALKS.
SEE YOU THEN.