>> OKAY, GOOD MORNING,
EVERYBODY.
THIS IS PANKAJ QASBA.
WE'LL START WITH OUR SYMPOSIUM
7.
WE HAVE TWO, 7 AND 8.
SO THIS PARTICULAR ONE IS
SYSTEMS BIOLOGY AND OTHER
APPROACHES OF SICKLE CELL
DISEASE.
SO WE HAVE YOU'LL SEE
INTERESTING PRESENTATIONS AND
BIOLOGY APPROACHES FOR SICKLE
CELL AND SPLEEN DISEASE AND ALSO
FOR GENE THERAPY CAMPAIGN FOR
SICKLE CELL FROM SCDAA AND ALSO
HEAR FROM ASH PEOPLE.
AND ALSO INFLUENCE MUCH SEX
HORMONES AND INFLUENCE OF MENSES
ON WOMEN AND METABOLIC
PROGRAMMING AND MACROPHAGES.
THERE'S A WHOLE VARIETY OF
PRESENTATIONS AND PROTOCOLS FROM
ALIGN TRIALS AND SYMPOSIUM 8
WILL BE ESSENTIALLY ALL UPDATES
FROM ASH AND FROM JULIE KANTER
ON THE NATIONAL ALLIANCE FOR
SICKLE CELL CENTERS AND CENSUS
RECOMMENDATIONS.
LET'S GET STARTED.
OUR FIRST PRESENTATION TODAY IS
AN INTEGRATED IN SILICO, IN
VIVO, EX VIVO FUNCTION OF SICKLE
CELL DISEASE.
THE FIRST PRESENTER IS PIERRE
BUFFET FROM PARIS.
>> HELLO.
I HOPE YOU CAN HEAR ME WELL.
>> WE CAN.
PLEASE GO AHEAD.
>> FIRST I'M SO GRATEFUL TO BE
WITH YOU EVEN IF IT'S SADLY NOT
IN PERSON.
ORGANIZING THIS IN FRANCE IS NOT
EASY IN SUMMER.
I'LL START WITH THE STAGE IN
PLACE AND THEN GEORGE EM
KARNIADAKIS CAN TWO DEEPER INTO
IN VITRO AND IN SILICO
APPROACHES.
LAST YEAR WE PRESENTED FROM
RESULTS OF CHILDREN WITH SICKLE
CELL DISEASE AND THIS YEAR I'LL
BROADEN THE SCOPE TO WHAT WE'VE
DONE IN MALARIA DO SEE HOW
THINGS DONE THERE WILL HELP US
UNDERSTAND AND TACKLE SICKLE
CELL DISEASE.
AS YOU SEE THE SPLEEN IS A
FILTER FOR RED BLOOD CELLS AND
THEY ARE PLAY A ROLE SQUEEZING,
TRAPPING, JAMMING MANY RED
CELLS.
LET ME TAKE YOU BACK TO
FILTRATION OF RED BLOOD CELLS.
AS YOU THINK MOST OF YOU KNOW,
THE WHITE PULP IS FOR ADAPTIVE
IMMUNE RESPONSE.
I WILL NOT TALK ABOUT THIS TODAY
AND FOCUS ON RED PULP AND
FILTRATION OF CELLS.
WHEN YOU LOOK AT THE MICROSCOPY
OF THE HUMAN SPLEEN THE SIZE OF
A FIST APPROXIMATELY YOU HAVE
MICROSCOPY.
WHITE NODULES WHICH CORRESPOND
TO LYMPHOID NODULES AND THE RED
SPONGY TISSUE WHERE THE
FILTRATION OF RED CELLS TAKES
PLACE.
IF WE LOOK AT THAT ON ELECTRONIC
MICROSCOPY FIRST LOOK AT THE
DRAWING ON THE TOP LEFT OF THE
SLIDE.
SO THIS IS A DRAWING OF THE
SMALL VEINS THAT ACT AS A
FILTER.
ENDOTHELIAL CELLS COLORED IN
BLUE ARE ELONGATED AND THEY DO
NOT HAVE A BASAL MEMBRANE SO RED
CELLS WILL GO FROM OUTSIDE TO
INSIDE YOU SEE THEM ENTERING AND
SQUEEZING BETWEEN THE
ENDOTHELIAL CELLS AND SEE THE
EQUIVALENT ON THE TOP.
THIS VERY TINY SQUEEZING OF RED
CELLS BETWEEN THE ENDO THELIAL
CELLS AND YOU SEE THE RED CELLS
SQUEEZING AND SEE THE INTENSE
DEFORM OF THE RED CELLS AS IT
GOES.
THANK YOU FOR LAUNCHING THE
FIRST ANIMATION IN SILICO BY THE
TEAM OF GEORGE EM KARNIADAKIS
WHICH IS THE ONLY WAY WE HAVE TO
LOOK AT THIS MOVING BECAUSE WE
DON'T HAVE A TOOL TO LOOK AT
THAT IN VIVO IN HUMANS.
I WAS NOT SURE I WOULD BE ABLE
TO LOOK AT THE VIDEOS SO THESE
ARE SNAPSHOTS.
THE SECOND FILTRATION DEVICE.
WE SAW THE MECHANICAL
DEFORMATION OF RED CELLS BUT THE
RED PULP IS FULL OF MACROPHAGES
HERE IN ORANGE WHICH ARE GOING
TO BE ABLE TO RETAIN THE RED
CELLS.
YOU CAN SEE THE PROCESS AND IF
YOU CAN LAUNCH THE VIDEO OR
SWITCH TO THE NEXT PICTURE.
YOU SEE THE RED CELL CONTAINS
AND THE FOLLOW-UP IS GOING
EXPELLED AND THE RED CELL
CONTINUES IN PROCESS AND USED TO
TEST SPLEEN FUNCTION.
SO THE WAY WE STUDIED THAT WAS
BY LAUNCHING AN EX VIVO SPLEEN
DIFFUSION SYSTEM.
YOU SEE THE SPLEEN IN THE BLUE
RESERVOIR THIS PUTS THE MARINE
IN CIRCULATION AND MAINTAINS ITS
FUNCTION ABOUT TWO HOURS SO WE
TEST THE PITTING PROCESS.
WE CAN SEE THE PITTING PROCESS
OCCURRING.
THIS IS THE BLUE PICTURE AT THE
BOTTOM WITH THE BROWN BODY BEING
EXPELLED AS THE RED CROSSES THE
SPLEEN FILTER.
SO WE USED THE SEEM HOW IT WAS
ABLE TO BE INFECTED.
TWO STAGES THE EARLY STAGE AND
THE RED VERSION ON THE TOP RIGHT
AND THE MATURE FORMS BIGGER AND
THE MATURE FORMS WERE FULLY
RESTAI
RESTAINS THIS IS TIME OF
DIFFUSION ON THE X AXIS AND HALF
OF THEM WOULD BE RETAINED BY
MECHANICAL RETENTION.
SOW IS THE SPLEEN IS SPLEEN IS
ABLE TO RETAIN AND DESIGN A WAY
TO FILTER RED CELLS IN A SPLEEN
LIKE WAY.
TO DO SO WE USED THESE MIMICKING
THE SIZE AND IF PUT POPULATION
OF RED CELLS CONTAINING A SUB
POPULATION OF INFECTED RED CELLS
IF YOU COME WITH A DRUG THAT
FILTERS THIS ONLY THE INFECTED
RED CELLS IMPACTED BY THE DRUG
WILL BE RETAINED WHEREAS ALL THE
OTHER RED CELLS WILL BE ABLE TO
FLOW THROUGH.
SO THE MICRO FILTRATION IS THE
BEST MIMIC WE HAVE WE TESTED
THIS FOR HIGH THROUGHPUT
SCREENING AND WE USE THIS TO
SCREEN DRUGS AGAINST THE MALARIA
PARASITES.
SO WE COULD SCREEN ALMOST 13
DRUGS FROM A REPURPOSING LIBRARY
CALLED REFRAME.
WE GOT 112 ACTIVE DRUGS THAT
STIFFEN INFECTED RED CELLS, 76
WERE CONFIRMED AS ACTIVE AND 3
ARE VERY INTERESTING BECAUSE
THEY'RE ONLY ADMINISTERED AND
SAFE.
THE CONCLUSION OF THE APPROACH
IS YOU CAN USE THE FILTRATION
SYSTEM THAT MIMICS THE SPLEEN TO
FIND DRUGS SPECIFICALLY ACTIVE
ON SOME RED CELL SUBPOPULATION.
AGAIN TO CONFIRM THE SYSTEM IS
REALLY MEANINGFUL IN TERMS OF
PATHOPHYSIOLOGY WE USED IT ON
OTHER RED CELL DISEASES AND THE
MOST WELL KNOWN IN TERMS OF
MECHANICAL RETENTION AND WHERE
RED CELLS BECOME SPHERICAL AND
LOSE SURFACE AREA AND THEY ARE
RETAINED UP STREAM AND ON THE Y
AXIS IS THE RETENTION RATE BY
THE SYSTEM AND RED CELLS ARE NOT
RETAINED AND RED CELLS ARE
RETAIN AND THE CORRELATION ON
THE Y AXIS AND SURFACE AREA OF
RED CELLS THAT CORRESPOND ARE
STRONG CONFIRMING LONG STANDING
THEORY THAT SPHEROCYTE SHAPE
PREVENTS THE ABILITY TO CROSS
THE SPLEEN.
THIS IS RED CELLS WHERE YOU SEE
THE DECREASE IN THE PERIPHERAL
BLOOD OF THE PATIENT WHEREAS
ACTIVITY INCREASES IN THE SPLEEN
CONFIRMING THAT REALLY THE
SPLEEN IS RETAINING THE RED
CELLS.
IN ERYTHROCYTOSIS IS THE WAY IT
CAUSES ANEMIA AND REMOVING THE
SPLEEN RELIEVES ANEMIA.
THIS IS THE LANDSCAPE WE'VE BEEN
USING TO CONSOLIDATE WHAT WE
WILL BE DOING AND WHAT WE ARE
DOING IN SICKLE CELL DISEASE.
LAST POINT ON MALARIA, VERY
RECENTLY WE USED SPLENECTOMY OR
SAMPLES FROM SPLENECTOMIES IN
MALARIA ENDEMIC AREA OF
INDONESIA AND SHOWED THE SPLEEN
WEIGHT IS CORRELATE WITH THE
CONGESTION OF THE RED AND
CORRELATE WITH THE LEVEL OF
ANEMIA.
CLEARLY IN CHRONIC MALARIA,
SPLEEN CONGESTION IS THE CAUSE
OF ANEMIA LIKE IN SPEROCYTOSIS
AND COMPLICATIONS IN SICKLE CELL
DISEASE.
JUST TO REMIND THE SPLEEN
CONGESTION IN SICKLE CELL
DISEASE AS SHOWN BY BRUCE AND
COLLEAGUES AND MANY OTHERS
BEFORE, THIS PROCESS IS DELAYED
BY THE USE OF HYDROXYUREA.
SO THERE'S A CONNECTION BETWEEN
THE DIFFERENT COMPLICATIONS AND
SPLEEN CONGESTION IN SICKLE CELL
DISEASE WITH CLEARLY ACUTE
CONGESTION CAUSING THE
SEQUESTRATION CRISIS AND CHRONIC
CONGESTION WHICH CAUSES
INCREASED ANEMIA AND LOW GROWTH
IN THE CHILDREN.
NOW TO THE RECENT RESULTS.
WE ANALYZED IN PARALLEL TWO
COHORTS, 17 CHILDREN WITH SICKLE
CELL DISEASE END UP GOING
SPLENECTOMY BECAUSE OF
SEQUESTRATION AND THERE WAS A
CONTROL GROUP OF 12 ADULT
SUBJECTS SPLEN ECTOMIZED AND
THEN COMPARED THEM BY FILTRATION
AS I SHOWED YOU PREVIOUSLY.
SO THE MAIN RESULT WE OBSERVED
IS IF YOU LOOK AT THE CONTROLS
THE PERIPHERAL RED CELLS ARE NOT
RETURNING WHEREAS THERE'S 10%
MORE RETENTION IN THE SPLENIC
RED CELLS, THAT WAS EXPECTED THE
SPLEEN IS RETAINING ALL THE RED
CELLS AND AS FOR SICKLE CELL
DISEASE THE DIFFERENCE BETWEEN
42 PERIPHERY AND SPLEEN IS
AROUND 35%.
THREES A MARKED MECHANICAL
RETENTION OF RED CELLS IN THE
SPLEEN OF CHILDREN WITH SICKLE
CELL DISEASE.
AND WHEN WE LOOK AT THE SHAPE OF
THE RED CELLS IN THE SPLEEN,
THEY'RE ELONGATED OR SPHEROIC
AND CLEARLY THE HUMAN SPLEEN OF
CHILDREN WITH SPLENIC
COMPLICATION IS MECHANICALLY
RETAINING A LOT OF RED CELLS AND
THIS IS CONTRIBUTOR OF THE
CONGESTION AND COMPLICATION.
ONE LAST POINT OF THIS SLIDE
WHICH IS I THINK CRUCIAL WHEN
YOU LOOK AT THE RETENTION OF RED
CELLS IN THE PERIPHERY
CIRCULATING RED CELLS IN THE
CONTROLS OR IN THE CHILDREN
THERE ARE IDENTICAL.
MEANING THE SPLEEN IS STILL ABLE
TO PREVENT STIFF RED CELLS TO
STAY IN CIRCULATION.
PROBABLY PROTECTING THE
PERIPHERY FROM THE DAMAGES
CAUSED BY STIFF RED CELLS IN
CIRCULATION.
TO SUMMARIZE THIS IN SICKLE CELL
DISEASE IS IF WE CAN ACT ON
SQUEEZING AND DROPPING AND
RESTORE THE ABILITY WITH DRUGS
WE'LL BE ABLE TO INTERRUPT THE
PATH TOWARDS SPLENIC
COMPLICATION.
THE IDEA IS YOU CAUSE JAMMING
AND THAT CAUSES SICKLING AND YOU
HAVE THE CRISIS WHICH EVENTUALLY
LEADS TO SPLEEN FIBROSIS AND
LOSS OF SPLEEN FUNCTION.
NOW, IF USING THE DRUG YOU'LL BE
ABLE TO RESTORE THE ABILITY OF
NORMAL RED CELLS THEN YOU WILL
PREVENT THE SPLENIC
COMPLICATIONS.
TO DO SO WE WANT TO USE THE
SCREENING SYSTEM WE USE IN
MALARIA BUT INSTEAD OF USING
DRUGS THAT STIFFEN PARASITES WE
WANT DRUGS THAT WOULD HELP
RESTORE THE DEFORMABILITY OF RED
CELLS.
SO THE IDEA IS THAT BY SAVING
RED CELLS WE'RE ABLE TO SAVE THE
SPLEEN TO MAINTAIN THE FUNCTION
AND TO BE MORE SCIENTIFIC THE
IDEA OF DRUG IS TO SAVE THE
SPLEEN AND PREVENT SPLENIC
COMPLICATION.
AND CLEARLY THE REASON WHY IT
WOULD BE USEFUL TO MAINTAIN IS
TO PREVENT COMPLICATION AND
PREVENT THE LOSS OF SPLEEN
FUNCTION THAT IN LARGE COHORTS
ARE SHOWN TO BE DELETERIOUS IN
ALL PATIENTS.
I WILL NOW HAND IT OVER TO
GEORGE EM KARNIADAKIS AND MING
DAO AND THANK YOU FOR INVITING
US TO THIS BEAUTIFUL MEETING.
>> THANK YOU FOR INVITING US
HERE.
I'LL CONTINUE THE IDEA BY
PIERRE.
THIS SLIDE WAS TRYING TO SHOW
THE REDUCED ABILITY THEIR RED
CELLS CAUSE MANY DISEASES
BECAUSE THE RED CELLS FROM TO GO
THROUGH SMALL CAPILLARIES AND
HAVE TO GO THROUGH MANY CYCLES
SO DEFORMABILITY IS VERY
IMPORTANT.
SO DURING THE OXYGEN DELIVERY
AND CARBON DIOXIDE TAKING FROM
THE TISSUE BACK TO LUNG, SO ALL
THESE GIVES RED CELL THE FATIGUE
OF REPEATED HYPOXIA CYCLES.
BOTH DEFORMABILITY LIKE
MECHANICAL CHALLENGE CYCLES
VERSUS HYPOXIA CYCLES ARE
FATIGUE AND THEY MAY DAMAGE THE
RED CELLS ESPECIALLY SICKLE
CELL.
SO WE BUILT MICROFLUIDIC DEVICES
THAT CAN DO UNDER CONTROLLED
HYPOXIA AND MEASURE
DEFORMABILITY IN SITU.
SO WE HAVE A SINGLE CELL
MICROFLUIDIC BASED PLATFORM THAT
CAN INDUCE SINGLE AND MULTIPLE
HYPOXIA CYCLES AND IMPOSE IN
SITU MECHANICAL LOAD AND TEST
RED CELL UNDER REPEATED HYPOXIA
AS WELL REPEATED MECHANICAL
CHALLENGES.
WHERE HE STUDY SPLEEN ON THE
DEVICE.
PIERRE ALREADY TOLD US THE
IMPORTANCE OF SPLIT RETENTION
AND THE MACROPHAGE SPEROCYTOSIS
BOTH ARE IMPORTANT BECAUSE
BECAUSE THEY NEED TO BE IN
BALANCE IN THE SPLEEN.
IF THE ACCUMULATED RETENTION
WILL REMAIN THEN THE SPLEEN WILL
BE CLOGGED AND BLOCKED.
THAT WILL CAUSE SEQUESTRATION
PROBLEM OR CRISIS.
SO ON THE TOP IS FROM PIERRE'S
PAPER THAT SHOWING IN THE SPLEEN
YOU DO SEE CELLS SICKLE UNDER
HYPOXIA.
BOTTOM IS THE IDEA THAT WE WILL
STUDY USING SEPARATED SO-CALLED
M CHIP AND S CHIP AND S CHIP
WILL PRESENT THE DEVICE THAT
MIMIC THE RETENTION FROM THE
SPLENIC SPLIT.
FOR THE M FILTER OR M CHIP WE'RE
TRYING TO STUDY THE RETENTION
AND PHAGOCYTOSIS OF THE
MACROPHAGES.
THESE ARE THE PHYSICAL DEVICES
AS SHOWN THE DEVICE WITH THE
FILTER SLITS.
THIS IS THE M CHIP WE'LL PUT
MACROPHAGES AND STUDY UNDER
HYPOXIA HOW THE PROCESS WILL BE
AFFECTED.
SO THIS BLUE CURVE SHOWS THE
SICK
SICKLED FRACTION AND THE BLUE
SHOWS THE OXYGEN.
THE GREEN IS THE SICKLE
FRACTION.
SO UNDER THIS HYPOXIA CYCLE
YOU'LL SEE THE SICKLE FRACTION
GOES UP GRADUALLY AND THEN IF WE
PUT THE OXYGEN BACK IT WILL
UNSICKLE.
SO THE SICKLE FRACTION WHEN THE
OXYGEN LEVEL GOES UP THE SICKLE
FRACTION WILL DROP.
SO NEXT -- THIS IS THE
EXPERIMENT UNDER HYPOXIA AND
MORE AND MORE CELLS TRAP AND
WHEN YOU PUT BACK THE OXYGEN AND
WE PLAY IT AGAIN AND THEN UNDER
HYPOXIA YOU SEE MORE AND MORE
CELLS GETTING TRAPPED.
WHEN YOU PUT OXYGEN BACK THESE
ARE UNSICKLED AND DEFORMABLE
AGAIN.
THESE ARE THE DIGITAL TWIN ON
THE BOTTOM GEORGE WILL SHOW
MORE.
SO WE HAVE THE DEVICE TO DO
MULTIPLE CYCLES THE HYPOXIA
CYCLES AND THE TIME ON THE LEFT
VERSUS OXYGEN LEVEL.
WE CAN CHANGE THE TIMING OR SO.
WE CAN SEE THE SICKLE FRACTION
WILL CHANGE OVER TIME AND VERY
HETEROGENEOUS THOUGH THE BLOOD
IS FROM A SINGLE PATIENT.
THERE'S HETEROGENEITY IN THE
PATIENT AND WE CAN TRACK USING
THE ASSAY AND THEN WE RECENTLY
BUILD A BASE AUTOMATED SICKLING
KINETIC MEASUREMENT.
IT USED TO BE WE HAVE TO COUNT
MANUALLY.
IT'S VERY PAINFUL BUT NOW WE
HAVE A METHOD TO DO IT
AUTOMATED.
THE QUESTION IS WHAT IF WE USE
THE ANTI-SICKLING DRUG APPROVED
BY PFIZER TO DO THE STUDY AND
WITH DIFFERENT MODIFICATION THE
PERCENTAGE ON THE LEFT MEANS
MODIFICATION LEVEL MEANS THE
PERCENT OF HEMOGLOBIN MODIFIED
BY THE DRUG.
THE MECHANISM IS TO INCREASE THE
OXYGEN AFFINITY.
ON THE RIGHT PANEL SHOWS THE
SICKLE FRACTION VERSUS TIME.
THIS IS SICKLING KINETICS UNDER
OUR HYPOXIA AND ON THE BOTTOM IS
THE PERCENT MODIFICATION YOU SEE
ALMOST NO SICKLING AT ALL BUT IN
BETWEEN 30% IS THE IDEAL
SITUATION ACHIEVED IN VIVO
BECAUSE YOU DON'T WANT THIS TO
BE THIS TO BE TOO MUCH BECAUSE
THE RED CELL WILL DELIVER TO
DELIVER OXYGEN IF THE AFFINITY
IS TOO MUCH.
30% YOU STILL SEE SIGNIFICANT
REDUCTION OF SICKLE FRACTION
VERSUS TIME AND THAT'S THE
BEAUTY OF THIS ANTI-SICKLING
DRUG.
SO IF THE QUESTION IS IF UNDER
REPEATED HYPOXIA CYCLES WHAT
HAPPENS?
THESE ARE THE RESULTS.
EACH IS TAKEN 20 SECONDS IN THE
HYPOXIA CYCLE AND IN THE X AXIS
YOU CAN SEE THERE'S SIGNIFICANT
REDUCTION OF SICKLED FRACTION
DUE TO DRUG TREATMENT.
IT'S THE LOWER GREEN BARS AND
THE BLUE BARS ARE THE CONTROL.
YOU CAN SEE THE VOXELOTOR HELPS
EARLY ON.
THIS IS AT 40 SECONDS.
SO THIS IS BOTH VERY EARLY STAGE
YOU CAN SEE IT'S ALREADY
SIGNIFICANTLY REDUCED SICKLED
FRACTION AND THAT ALSO PERSISTS
WITH SOME MANY CYCLES UP TO 30
CYCLES WE DID THE REDUCTION HAS
BEEN VERY SIGNIFICANT.
SO THE DRUG REALLY HELPS.
OKAY.
HERE IS A STUDY OF NORMAL RED
CELLS THROUGH THE SPLEEN SLITS.
YOU CAN SEE THEY GO THROUGH
PRETTY EASILY.
IF FOR SICKLE CELLS UNDER
NOMOXIA AND THEY'RE STIFFER YOU
CAN SEE THIGH HAVE BEEN BLOCKED
MORE THAN THAT ONE BUT STILL
MANY CELLS CAN GO THROUGH UNDER
NORMOXIA AND YOU CAN SEE THE
DEFORMED SICKLE CELLS WE'LL
BLOCK THE SLITS QUICKLY.
THEY PROVIDES US HISTOLOGY OF
THEIR STUDY ON THESE.
THIS IS THE NORMAL SPLEEN PLUS
HEALTHY RED CELLS COMPARED TO
THE NORMAL FLUIDIC DEVICE AND
WITH NORMAL THERE'S
SEQUESTRATION BUT NOT TOO MUCH
COMPARED TO SICKLE RED CELLS IN
THE SPLENIC CRISIS YOU SEE THE
SEQUESTRATION.
THESE ARE CONFIRMED BOTH THE
PERCENT OF OPEN SLITS AND THE
RED IS UNDER THE DE-OXYGENATED
CONDITION AND BLOCKING THE
SPLITS QUICKLY.
UNDER NORMOXIA IS NOT TOO BAD.
THESE ARE THE HEALTHY CONTROLS.
IF WE TAKE A SNAPSHOT AT 40
SECONDS XRAR THE CELLS IN THE
CONDITION UNDER HYPOXIA THERE'S
NO SIGNIFICANCE AND UNDER
CONDITIONS THERE'S HIGHER
RETENTION.
THE OPEN SLIT NUMBER DROPS.
THEN IF 234R HYPOXIA MOST OF
THESE -- MANY OF THE CELLS
SICKLE AND ARE VERY STIFF AND
CAN QUICKLY CLOG ALL THE SLITS.
AND WHAT HAPPENS IF WE HAVE THE
HYPOXIA BLOCKED AND PUT BACK
OXYGEN WHAT HAPPENS NEXT.
I BELIEVE WE WERE MIMICKING WHAT
WAS HAPPENING IN A SPLENIC
CRISIS.
DOCTORS PUT ON TRANSFUSION AND
THEN WE'LL GET THE OXYGEN IN THE
SPLEEN AND THEN THAT'S WHAT
HAPPENS WE RELIEVE AT LEAST
TEMPORARILY.
AND SITUATION FOR IN VIVO DRUG
TO PATIENTS.
HYPOXIA BLOCKING THE SLITS
QUICKLY AND DROP TO ZERO QUICKLY
BUT WITH VOXELOTOR TREATMENT THE
HIGHER OPEN SLITS REMAIN OVER
TIME.
THERE'S DEFINITELY VERY GOOD
RELIEF WITH THE VOXELOTOR
TREATMENT IN THE INITIAL
EXPERIMENT.
SO THERE'S ANOTHER SIDE OF THE
STORY.
WHAT HAPPENS WITH THE MACROPHAGE
TO THE BALANCE AND ADHESION
VERSUS DIFFERENT CONDITIONS
UNDER NORMOXIA AND HYPOXIA AND
THE MACROPHAGE NEXT.
YOU SEE THE VIDEO WE STUDIED THE
ADHESION.
THESE ARE ENHANCED FOR
ESPECIALLY ON THE HYPOXIA.
THE MACROPHAGE VERSUS DIFFERENT
CONDITIONS.
FOR HEALTHY CELLS UNDER
DEOXYGENATED CONDITIONS THERE'S
LITTLE TRACKING OF THE RED CELLS
BUT UNDER FOR SICKLE CELLS YOU
HAVE A HIGHER NUMBER OF CELLS
BEING TRAPPED AND ADHERED BY THE
MACROPHAGES.
UNDER DEOXYGENATED THE ADHESION
IS MORE ENHANCED UNDER HYPOXIA.
THEY'LL BE INGESTED BY THE
MACROPHAGES AND UNDER NORMOXIA
THEY'LL BE DIGESTED.
THIS TAKES 12 MINUTES AND 7
MINUTES AND THIS IS A SICKLE
CELL UNDER HYPOXIA BEING
INGESTED AND THIS IS BEING
DIGESTED NOT TOO SLOW BUT IN
MANY CASES HALF THE SICKLE CELLS
ARE EATEN OR INGESTED INSIDE THE
SICKLE AND THEY REMAIN HARD TO
DIGEST.
HALF STAY FOR HOURS NOT BEING
DIGESTED.
SO THIS WE BELIEVE IS A
BOTTLENECK DUE TO MANY OF THESE
ARE NOT EASY TO BE DIGESTED
THOUGH THEY INTERNALIZE QUICKLY.
THIS IS VERSUS DIFFERENT
CONDITIONS.
SICKLED CELLS UNDER HIGH BOX YA
ARE INGESTED PRETTY QUICKLY.
IF IT'S NOT SICKLED THEN THEY
PRETTY MUCH STAY SIMILAR AS
NORMOXIA CONDITION IF THE SICKLE
CELLS ARE NOT SICKLED.
SO SICKLED OR NOT SICKLED
THERE'S A DIFFERENCE IN THE SLOW
DIGESTION WILL BE BOTTLENECK.
SO WHEN THE INGESTED SICKLE CELL
HAS BEEN TAKEN IN IT CAN SLOW
DIGESTION BUT IF WE PUT OXYGEN
BACK ON WHAT HAPPENS?
YOU CAN SEE THIS IS A SICKLED
CELL UNSICKLED FIRST AND THEN
AFTER UNSICKLING IT CAN BE
DIGESTED RATHER QUICKLY.
SO IF YOU HAVE A WAY TO UNSICKLE
OR REDUCE THE SICKLING
PERCENTAGE IT WILL BE VERY
HELPFUL.
SO HERE'S A SUMMARY SLIDE.
WE BELIEVE FOR HEALTHY SUBJECTS
THE RETENTION VERSUS ELIMINATION
RATE WILL BE RELATIVELY SMALL
AND THEY WILL KEEP BALANCE.
UNDER STABLE SICKLE CELL DISEASE
SITUATION BECAUSE OF THE LOWER
DEFORMABILITY IN SICKLE CELLS
THEY'LL HAVE MORE SICKLE CELLS
BEING TRAPPED.
IF YOUR ELIMINATION BY
MACROPHAGES CAN KEEP UP THE PACE
THEN TAKING A LOT OF THESE STIFF
CELLS BUT THEY CAN -- YOU HAVE
ANEMIA BUT YOU MAY NOT HAVE MORE
SYMPTOM LIKE IN LARGE SPLEEN.
BUT HERE AS PIERRE WAS
MENTIONING, IF WE CAN INCREASE
THE DEFORMABILITY AND TOWARD THE
HEALTHY CONDITION WE REALLY CAN
PROBABLY GO BACK TO THIS AND
PREVENT DAMAGING AND THE
HYPERSPLENIC CONDITION IS WHEN
THE RETENTION RATE IS HIGHER
THAN WHAT THE MACROPHAGES CAN
HANDLE YOU'LL HAVE A LARGE
SPLEEN THAT CAN BE A MORE SEVERE
SITUATION.
IF THIS SITUATION PERSISTS AND
SUSTAINED WITH THE HIGHER
RETENTION RATE THAN THE
MACROPHAGE THEN IT WILL HAVE A
DEEPENING HYPOXIA AND WILL HAVE
MORE SICKLED CELLS AND THE
SLOWER INGESTION WILL MAKE THE
WHOLE THING INTO A VICIOUS CYCLE
AND IT COULD BE A
LIFE-THREATENING CRISIS.
IN BOTH CASES IF WE HAVE REDUCED
SICKLING PERCENTAGE AND ALSO WE
CAN SOFTEN THE CELLS WE CAN
ACTUALLY SOLVE THE PROBLEM FROM
THE BEGINNING.
THAT'S WHY WE MAY HAVE A HOPE TO
SAVE THE SPLEEN WITH THE DRUG.
SO THAT'S MY SUMMARY SLIDE.
SO WE ACTUALLY ESTABLISHED OUR
DRUG EFFICACY ASSAYS AND THIS
CAN ALSO DO THE TEST FOR US TO
TRY TO SCREEN DRUGS ACTUALLY.
SO HOPEFULLY WITH OUR TESTS AND
ASSAYS AND UNDERSTANDING, THERE
MAY BE DRUGS THAT CAN BE USED TO
SAVE THE SPLEEN.
HOPEFULLY WE CAN ACHIEVE THAT IN
WITH FUTURE STUDIES.
THANK YOU, THAT'S ALL.
>> THANK YOU VERY MUCH, MING AND
PIERRE.
THANK YOU.
SO HERE WE ARE IN ADDITION TO IN
VITRO AND IN VIVO STUDY WE DO IN
SILICO STUDIES AIMING TO BUILD
DIGITAL TWINS FOR ALL THE
RECEIVES IN SICKLE CELL ANEMIA
INCLUDING SUB CELLULAR
ALTERATION AND SUB CELLAR
MECHANICS AND DIGITAL TWINS AT
THE ORGAN LEVEL THE ARE RED
BLOOD CELLS LEVEL AND SHOW YOU
RESULTS OF THIS AND THE STUDIES
ARE BASED ON VERY SOPHISTICATED
MATHEMATICAL MODELS MOLECULAR
DYNAMICS WHERE ONE CAN DO THE
SAME MODELLING UNIVERSALLY FROM
ON DIFFERENT SCALES.
SO YOU BUILD DIGITAL TWINS AND
CONTINUALLY LEARN AND YOU CAN
SEE SO FAR WE HAVE PLENTY OF
DATA USING THE MICROFLUIDIC
EXPERIMENTS AT MIT AND STUDIES
OF PIERRE IN FRANCE.
SO EACH ONE PROCESS WE MODEL
FROM LEFT TO RIGHT THE
POLYMERIZATION AND RAD HEGES AND
MACROPHAGES AND ALSO DIGITAL
TWIN OF MACROPHAGE AND PAPER IN
A JOURNAL ON THE COVER OF THIS
JOURNAL BECAUSE OF THE
COMPLEXITY IN DEVELOPING THE
MODELS AND MAKE THEM REALISTIC
AND DIGITAL TWINS TO CONTINUALLY
LEARN.
AS AN EXAMPLE, STARTING WITH THE
SIN
SINGLE RED BLOOD CELL AND YOU
SEE THE FLUCTUATION AND TO CUT
THROUGH THE MIDDLE OF THE RED
BLOOD CELL YOU SEE THE
HEMOGLOBIN PARTICLES AND ON THE
BOTTOM YOU CAN SEE THE
POLYMERIZATION PROCESS CHA IS
GROWING IN THE MEMBRANE OF THE
RED BLOOD CELL SO THE MODELS
HAVE BEEN VALIDATED 10, 15 YEARS
USING THE LAB AT MIT.
HERE'S AT THE SUBCELLULAR LEVEL
INCLUDING IN THE MEMBRANE OF ALL
THE PROTEINS INVOLVED IN THE
PROCESS AND IT'S A VERY DYNAMIC
AND FAST PROCESS THIS
POLYMERIZATION RECRUITING MORE
HEMOGLOBIN MOLECULES AND IT WAS
AN EXERCISE OF DEVELOPING
METHODS ON THE FLY AND IT'S A
DYNAMIC PROCESS WHICH WE DID A
FEW YEARS AGO.
THIS IS OXYGENATION AND YOU CAN
SEE THE DIGITAL TWINS TOTALLY
MIMIC THE EXPERIMENT.
YOU CAN TRAIN THE RED CELLS TO
BE SUBJECT TO THE FORMATION
ACCORDING TO THE LEVEL OF
OXYGENATION AND WITH DATA WE
HAVE THE DIGITAL TWINS OF THE
REALITY.
AND THESE ARE THE SLITS OF THE S
KWHIP AND -- S CHIP OF THE
DIGITAL TWIN AND MEASURE THE
VELOCITY AND HUNDREDS OF
MICROBES PER SECOND AND
CONSIDERED GOOD AGREEMENT AFTER
THEY'VE BEEN CALIBRATED AFTER
MANY MANY YEARS OF THIS TYPE OF
WORK.
AND HERE THE SLIDE SHOWED ALL
THREE INTEGRATION WE HAVE AS THE
TITLE OF THE TALK YOU SEE THE
IMAGE WHERE WE SEE HOW CLOUDED
IS THE SLITS AND THIS IS
REPEATED IN VITRO WHERE WE CAN
SEE ACCUMULATION OF THE PRESSURE
OF RED BLOOD CELLS IN FRONT OF
THE SLITS AND THIS IS THE
INTEGRATION HOW WE BUILD THIS
BECAUSE IT'S BASED ON BOTH IN
VIVO AND IN VITRO IN DATA.
AND THE COMPLICATED INTERACTION
AND YOU CAN CLICK ONCE A COMPLEX
INTERACTION BETWEEN THE
MACROPHAGES AND THE RED BLOOD
CELLS.
YOU CAN SEE THEY COME IN
DIFFERENT SHAPES AND SOME ADHERE
AND IT'S A COMPLEX ADHESION AND
COMPLEX PROCESS BUT WE TRY TO
MIMIC AND QUANTIFY WITH
COMPARISONS AND EXPERIMENTS IN
THE PAPER.
SO THE NEXT PROCESS FOR
MACROPHAGES HOW WE SIMULATE
ENGULFMENT.
AND HERE WE HAVE EXPERIMENTS
WITH MICROBEADS TO MIMIC OUR
CY
CYTOSIS AND THEY HAVE AN ACTIVE
AREA THAT GOES AND CAPTURES THE
BEADS.
MOST IMPORTANTLY AND THAT'S WHY
THE SIMULATION IS HELPFUL.
WE CAN QUANTIFY THE ADHESION
ENERGY REQUIRED.
THAT'S SOMETHING THAT CANNOT BE
DONE FOR FULL OR PARTIAL
ENGULFMENT IN THE BOTTOM LEFT.
IF YOU CAN CLICK A COUPLE TIMES.
WHAT YOU SEE IS RA PLYING THE
MICROBEADS TO DELEGATED SHAPES
THE ONES THAT STAY BEHIND AND
AND WE MIMIC THERE'S EXPERIMENTS
AT THE LAB AT MIT AND UNDER
NORMOXIA THEY'RE DEFORMABLE AND
UNDER GO DRASTIC DEFORMATION AND
BECOME SMALLER BEFORE BEING
ENGULFED IN CONTRAST UNDER
HYPOXIA DURING THE PROCESS OF
SI
SITOSIS IS DIFFERENT AND WE'RE
ABLE TO QUANTIFY THAT.
SO HERE'S A QUANTIFICATION I WAS
TALKING ABOUT.
WE SEE ON THE LEFT WE NOW HAVE
THE EXPERIMENTS AND ADHESIVE
STRESS AND THE AMOUNT REQUIRED
FOR FULL ENGULFMENT AND WE SEE
HERE ON THE LEFT YOU CONSIDER
THE FLEXIBLE IS THE ADHESIVE
STRESS IS THE LARGEST OPPOSED TO
ELONGATED AND RIGID WHICH CAN BE
ENGULFED FASTER.
ON THE RIGHT WE GO BACK TO
SOMETHING THAT PIERRE TALKED
ABOUT SO WE HAVE THE RED BLOOD
CELLS GOING THROUGH THE SPLIT
BUT AS THEY BECOME MORE
SPHERICAL WE SEE THE RETENTION
RATE INCREASES.
CORRESPONDINGLY THE SAME SURFACE
AREA OF VOLUME WILL BE A
DETERMINATE OF PARTIAL OR FULL
ENGULFMENT.
HERE WE SHOW RED BLOOD CELLS AND
WE'RE ABLE TO COMPARE THE
CONTROLS TO QUANTIFY EXACTLY THE
LEVEL OF ADHESIVE STRESS AND THE
SURFACE AREA WHICH IS A DOUBLE
DETERMINATANT -- DETERMINATE FOR
THE MACROPHAGES AND THIS
QUANTIFIES THE PROCESS.
HOWEVER, THE MACROPHAGES WE
SHOWED HOW WE BUILD MACROPHAGES
THAT MIMIC THE REAL MACROPHAGES
BUT THEY ARE BASED ON
MACROPHAGES SHOWN IN THE UPPER
RIGHT PICTURE IT'S VERY VIVID.
THE QUESTION IS CAN WE BUILD A
TRUE DIGITAL TWIN OF THAT WITH
WHICH HAS PSEUDOPODS INSIDE THE
CELL AND RANDOMLY OR WHEN THEY
TRIGGER THEY PROTRUDE.
FOR US THAT WAS THE LATEST WHERE
WE WERE ABLE TO SHOW WE CAN
BUILD THIS TYPE OF PSEUDOPODS.
HERE WE HAVE A MODEL WHERE THE
MEMBRANE AND THE CYTOSKELETON
ARE SHOWN DIFFERENTLY AND IT
PLAYS AN ACTIVE ROLE IN THE
PSEUDOPODS AND IF YOU CLICK
YOU'LL SEE HERE HOW YOU HAVE
THIS PSEUDO POD AND SEE THE BLUE
DOTS FROM THE CYTOSKELETON RAP
TOURS AND ENGULFS THE RED BLOOD
CELLS AND AS IT GOES INSIDE FOR
DIGESTION THERE'S A
RECONNECTION, A LINKING OF THE
FILAMENTS OF THE MACROPHAGE.
A COMPLEX BUT WE'RE AT THE POINT
WHERE WE HAVE A TRUE DIGITAL
TWIN OF THE MACROPHAGE FOR THE
FIRST TIME.
THIS IS ALSO SHOWN HERE IN THE
NICE VIDEO.
FROM WORK FROM ISRAEL SHOWING
THE PSEUDO PODS ARE ISSUING THIS
AND RANDOM PROTUGS OF PSEUDO
PODS WE WERE TRYING TO MIMIC IN
THE DIGITAL TWIN FINALLY WE HAVE
A DIGITAL TWIN OF THE SPLEEN
FROM PIERRE'S GROUP IN FRANCE WE
TRIED TO HAVE A GEOMETRICALLY
SIMILAR DIGITAL TWIN AND WE
CHECKED THE GEOMETRY.
WE OF COURSE WANT TO SIMULATE
THE CONDITIONS OF WHICH RED
CELLS GO THROUGH AND RETAVEND
AND CAUGHT BY THE MACROPHAGES.
-- RETAINED AND CAUGHT BY THE
MACROPHAGES.
WE HAVE THE MACROPHAGE IN FRONT
OF THE SLITS.
AND HERE THERE'S A POINT YOU CAN
CLICK THE MACROPHAGES CAPTURE
WHAT IS BLOCKED BY THE SLIT.
IN THE MIDDLE WE CAPTURE THE
CELLS AND SLITS IN CONTRAST YOU
HAVE A HEALTHY FLOW ON THE RIGHT
YOU SEE THE RED CELLS GO THROUGH
AND THE RIGHT DIGITAL TWIN.
THE LAST ONE WE CAN QUANTIFY AND
WHAT WE HAVE HERE IS THE EFFECT
OF THE CHANGES.
SO WE HAVE A TOTAL SYSTEMATIC
COMPARISON WITH EXPERIMENTAL
DATA OF DIFFERENT LEVELS OF RBC
AND IN SUMMARY WE HAVE PRESENTED
AN INTEGRATED IN VIVO, IN VITRO,
IN SILICO STUDY AND GOING
FORWARD WE'RE LOOKING HOW TO
SAVE THE SPLEEN AS PIERRE AND
MING TALKED ABOUT AND WHAT DRUGS
IN PARTICULAR OF THE RECENT
DRUGS WOULD BE MOST EFFECTIVE
AND USING BOTH IN VITRO AND IN
SILICO EXPERIMENTS WE CAN
DISSECT THE MECHANISMS BY WHICH
THIS HAPPENED.
THANK YOU VERY MUCH.
YOU TOOK US FROM VALIDATING IN
THE LAB IN THE SPLEEN AND MOVING
AT THE MICROFLUIDIC LEVEL AND
DOING COMPLEX PATH TO CREATE
BEAUTIFUL DIGITAL TWINS TO
VALIDATE YOUR EXPERIMENTS.
QUESTIONS?
>> IN THE PAST THEY TALKED ABOUT
TIME AND HAVE YOU LOOKED AT THE
TIME IN YOUR EX VIVO CONDITIONS
AND ARE YOU SUGGESTING IT
DOESN'T MATTER WHETHER THE
SICKLE CELLS ARE REVERSIBLY OR
NOT REVERSIBLE STILL
CONTRIBUTING?
>> WE LOOKED AT THIS A LITTLE
BIT.
IN FACT THE SO-CALLED
IRREVERSIBLE SICKLE CELL THE
SICKLE HEMOGLOBIN STILL
POLYMERIZE AND UNPOLYMERIZE
DURING THE HYPOXIA AND NORMOXIA
CYCLES SO BECOME MORE STIFFER
EVEN THE IACs BECOME STIFFER
DURING UNDER HYPOXIA.
THE IACs BY ITSELF START AS MORE
RIGID THAN THE OTHERS AND BY
THEMSELVES MAY NOT PASS THE
SLITS THAT ARE EASIER TO BE
ELIMINATED BUT OTHERWISE THEY
STILL GO THROUGH IN OUR IN VITRO
STUDY THEY STILL GO THROUGH THE
POLYMERIZATION PROCESS.
>> WHAT IS THE ADMINISTRATION OF
OXYGEN?
>> MAYBE THE ANSWER CAN BE
ANSWERED BY PIERRE.
>> GOOD QUESTION.
THE ANSWER AT THE MOMENT IS WE
DON'T KNOW.
WE DON'T HAVE DIRECT
MEASUREMENTS IN THE COURSE OF
THE LEVEL OF OXYGEN.
WE DON'T KNOW HOW DEEP GOES THE
HYPOXIA.
IT'S PROBABLY PRETTY MILD
BECAUSE THE SPLEEN RECEIVES MUCH
MORE BLOOD FLOW THAN IT NEEDS
FOR METABOLIC REQUIREMENTS AS A
FILTERING ORGAN.
BUT THE TRUTH IS WE CONFER ONLY
INDIRECTLY, SORRY.
>> ONE ADDITION.
I THINK WE ACTUALLY HAVE MORE
EXPERIMENTS DOWN AT MILD HYPOXIA
THAT MAY BE MORE SIMILAR TO MOST
CASES IN VIVO.
>> ONE COMMENT, IF I MAY.
MOST OF WHAT WE HAVE SHOWN IN
MECHANICAL RETENTION OF NORMAL S
IS UNDER NORMOXIA.
THERE IS NOT ONLY SICKLING AND
MECHANICAL RETENTION IN SICKLE
CELL DISEASE CASE.
>> GREG COTTO FROM CSL.
CONGRATULATIONS THIS IS FABULOUS
PROGRESS.
THERE'S A STRUCTURAL NUANCE I'M
WONDERING ABOUT IN THE IMAGING
OF MACROPHAGES ADHERING TO
SICKLE CELLS, IT APPEARS THE
LEGEND EDGE OF THE INTERACTION
IS ALWAYS ONE OF THE POINTS OF
THE CELL.
AND I WONDERED IF YOU HAVE
INSIGHTS WHETHER IT'S
INTERACTION THROUGH RECEPTORS OR
ANY OTHERS?
IT'S REMINISCENT OF WHAT MING
SHOWED IN THE PAST OF THE
LEADING EDGE ADHESION TO
FIBERNECTIN IN TERMS OF SICKLE
CELLS.
>> THANK YOU.
I DON'T THINK WE HAVE LOOKED
INTO THAT YET.
I THINK YOU HAVE A VERY GOOD
SUGGESTION.
MAYBE WE SHOULD TAKE A LOOK AND
TRY TO SEE IF THAT HAPPENS.
THANK YOU.
>> CAN I ADD SOMETHING HERE
BECAUSE WE HAVE BEEN WORKING
WITH A GROUP AT JOHNS HOPKINS
AND HAVE RECENTLY PUBLISHED A
PAPER ON THE SIGNALLING
MECHANISM.
FOR THAT WE ARE TRYING TO EMBED
THE PROCESS WITH THE MECHANISM
CURRENTLY BUT PUBLISHED THIS
PAPER WHERE WE INCLUDE THE
SIGNALS AND OTHER LIGANDS
RECEPTORS THE MECHANISM FOR THIS
AND NOW WE ARE IN THE PROCESS OF
INTEGRATING THE SIGNALLING AND
THE BIO MECHANICAL ASPECT OF
CYTOSIS I SHOWED YOU.
>> DREXEL UNIVERSITY.
THIS WAS A BEAUTIFUL
COMPREHENSIVE STUDY AND ALSO
WANT TO POINT OUT THAT THE
MOVIES THAT GEORGE SHOWS ARE SO
COMPELLING, IT'S DECEPTIVE TO
KNOW HOW CRAZY THE COMPUTATIONAL
LEVELS ARE TO SHOW ALL THAT
STUFF.
THE POINT I WANTED TO MAKE TO
YOU IS REGARDING THE VOXELOTOR
AND IT'S IMPORTANT TO COMPARE
THAT AND NON-TREATED CELLS AT
CONSTANT OXYGEN DELIVERY RATHER
THAN CONSTANT P.O.T. BECAUSE
VOXELOTOR AND THE COMPARISON IS
FOR THE GIVEN A OF OXYGEN HOW
WELL HAS VOXELOTOR DONE COMPARED
TO THE CONTROLS.
>> THANK YOU.
THAT WAS A HARD EXPERIMENT TO DO
BUT WERE THINKING HOW TO MANAGE
THAT.
>> YOU GUYS ARE AT M.I.T.
YOU'LL FIGURE IT OUT.
>> THANK YOU.
YES, WE HAVE ONLINE QUESTIONS.
>> THANK YOU FOR GREAT TALKS.
YOU LOOKED AT MACROPHAGES WITHIN
THE SPLEEN.
WHAT ABOUT OTHER IMMUNE CELLS
AND SPECIFIC COMPONENTS OF THE
SPLEEN.
ARE THERE DIFFERENCES BETWEEN
THE RED AND WHITE PULP?
>> THERE'S FIBROSIS IN THE
PROPORTION OF KIDS AND THERE'S A
LOSS OF WHITE PULP SO LIKELY
SOME DEFECTS IN ADAPTIVE
COMMUNITY AND RECENT RESULTS THE
SPLEEN IS STILL WORKING AND
THERE'S NO OBVIOUS IMPAIRMENT OF
IMMUNE CELLS AT THIS STAGE.
THIS IS THE PERIOD WHERE MOST
KEEN TO LOOK AT THE PROCESSES
NOT LATER ON.
THERE MAY BE MANY THINGS COMING
LATER IN THE EVOLUTION.
>> ANYMORE QUESTIONS?
GREAT?
IF THERE'S COMMENTS ON CHAT I'M
SURE GEORGE AND PIERRE WILL TAKE
A LOOK AT THAT.
WELL, THANK YOU VERY MUCH FOR
THIS AMAZING JOURNEY BETWEEN LAB
AND MICROFLUIDICS AND IN SILICO
AND WE'LL COME BACK TO EARTH AND
NATURAL HISTORY OF AVASCULAR
NECROSIS OF FEMME EERL HEAD IN
CHILDREN AND ADOLESCENTS WITH
SICKLE CELL DISEASE FROM
DR. KHALID ELBASHIR.
>> I HAVE NO DISCLOSURES.
AS WE HEARD IN SEVERAL
PRESENTATIONS THERE'S A LOT OF
GAP IN KNOWLEDGE IN MANY THINGS
IN DEVELOP.
-- IN SICKLE CELL.
AND I'D LIKE TO SHED LIGHT AND
THERE'S PROGRESSIVE CONDITION OF
SICKLE CELL DISEASE AND
OBSTRUCTION OF THE BLOOD BY THE
SICKLE RED BLOOD CELL LEADING TO
ISCHEMIA AND LOSS OF STRUCTURAL
INTEGRITY AND EVENTUALLY
COLLAPSE OF THE FEMORAL HEAD.
IT AFFECTS ABOUT 30% OF PEOPLE
LIVING WITH SICKLE CELL DISEASE
AND THE HIGHEST OF AVASCULAR
NECROSIS IS SS AMONG AFRICAN
AMERICANS AND WITH 41% HAVING A
VASCULAR NECROSIS.
THE PREVALENCE INCREASES WITH
AGE AND IMPACT OF AVASCULAR
NECROSIS IS MORE PRONOUNCED
AMONG ADULT.
IN THE ABSENCE OF INTERVENTION
THE COLLAPSE OF FEMORAL HEAD IN
90% OF PATIENTS WITHIN FIVE
YEARS AFTER THE ONSET OF
CLINICAL SYMPTOMS.
MEANING PAIN AND PROBLEMS.
AVASCULAR NECROSIS LEADS TO
REDUCED QUALITY OF LIFE
OBVIOUSLY AND POSSIBLY INCREASED
OPIOID UTILIZATION.
THERE ARE STILL GAPS IN
UNDERSTANDING THE DISEASE COURSE
AND MANAGEMENT OF AVASCULAR
NECROSIS DUE TO GAP IN RESEARCH.
AND THERE'S CLINICAL X-RAY AND
MRI AND YOU CAN SEE IN THIS
CARTOON HOW THE HIP IS GETTING
ANGRY AS THE DISEASE ADVANCE.
SO OUR GOAL IS TRY TO CAPTURE
THE DISEASE AS EARLY AS POSSIBLE
TO PROGRESSION TO COLLAPSE HIP
AND DEGENERATIVE DISEASE.
AT ST. JUDE WE'RE DOING STUDY OF
AVASCULAR NECROSIS TO
CHARACTERIZE THE CLINICAL RISK
FACTORS, BIOLOGICAL PARAMETERS
OF AVASCULAR NECROSIS OF THE
FEMORAL HEAD AND PROGRESSION OF
AVASCULAR NECROSIS AND WANTED TO
EXAMINE THE TWO GROUPS AND
IDENTIFY IF THERE IS ANY GENETIC
FACTOR LIKE POLYMORPHISM
DOCUMENTED THAT CAN INCREASE THE
RISK FOR AVASCULAR NECROSIS
AMONG PATIENTS WITH SICKLE CELL
DISEASE AND EXAMINE IF THERE'S A
RISK FACTOR MEANING
HOSPITALIZATION AND HOSPITAL
RE-ADMISSIONS.
WE ALSO WANT TO DETERMINE THE
FULL HIP REPLACEMENT AND MEASURE
THE TIME BETWEEN DIAGNOSIS AND
SURGICAL INTERVENTION.
AND LOOK AT AVASCUAR NECROSIS
USING HIP MRI.
WE LOOKED AT THE DATABASE IN
ST. JUDE BETWEEN PATIENTS
BETWEEN 2006 AND 2021.
AGE RANGES BETWEEN 0 AND 27
YEARS OLD.
AT LEAST THEY HAD ONE MRI FOR
SUSPECTED AVASCULAR NECROSIS AND
LOOKED AT MODIFIABLE AND
UNMODIFIABLE RISK FACTORS.
IN THE UNMODIFIABLE RISK FACTORS
WE LOOKED AT PATIENTS SEQUENCED
AND THIS IS ONGOING WORK TO LOOK
AT THE MORPHISM AND LOOKING AT
THOSE WITH AVASCULAR NECROSIS
AND THE CLINICAL AND LABORATORY
FACTORS SUCH AS HEMOGLOBIN F,
VITAMIN D AND BONE MARROW
DENSITY.
AND THE SAME FOR THE INDIVIDUALS
WITH NO AVASCULAR NECROSIS.
SO THE OUTCOMES WE'RE TRYING TO
SEE AT WHAT AGE IS AVASCULAR
NECROSIS IS PRESENT.
AND WHAT ARE THE DIAGNOSTIC
MODALITY USED TO DIAGNOSIS
AVASCULAR NECROSIS AND
RECOMMENDATION AT THE TIME
RECOMMEND JUST PHYSICAL THERAPY
AND COMPRESSOR REPLACEMENT AT
THE TIME OF PRESENTATION AND
ALSO THE YEAR BEFORE AND AFTER
INTERVENTION AND THE FREQUENCY
OF HOSPITALIZATION AND E.D.
VISITS AND OTHER COMPLICATIONS
OF AV AND THESE WHICH ARE MORE
BURDENED WITH SICKLE CELL
DISEASE AND LOOK AT
PSYCHOLOGICAL IMPACT TO MEASURE
WHETHER IT HAS INDUCED ANXIETY
OR DEPRESSION AMONG THE
PATIENTS.
AND SAME WITH THE PATIENT OF
AVASCULAR NECROSIS WITH NO
FEMORAL HEAD.
WE HAD A TOTAL OF 68 PATIENTS
WITH MRI FOR SUSPECTED AVASCULAR
NECROSIS OF THE FEMORAL HEAD.
OUT OF THE 68, 34 OF THEM WITH
AVASCULAR NECROSIS AND 34 HAD NO
AVASCULAR NECROSIS.
SO THE AGE WAS A LITTLE HIGHER
AMONG THE PATIENTS WHO HAD
AVASCULAR NECROSIS COMPARED TO
THE PATIENTS WHO DID NOT HAVE
AVASCULAR NECROSIS AND THEN
THERE WAS INCREASED LIKE IN MALE
PREVALENCE ABOUT ALMOST 68% OF
THEM WERE MALE.
THE HEMOGLOBIN F WAS HIGHER IN
PATIENTS WITH NO AVASCULAR
NECROSIS BUT NOT STATISTICALLY
SIGNIFICANT AND WE ASSUME
BECAUSE OF THE SMALL SAMPLE
SIZE.
ONE OF THE THINGS WE FOUND AND
WE STILL ARE GETTING DATA AND
ADDING MORE PEOPLE TO THE STUDY
THAT WE DID NOT FIND DIFFERENCE
IN HYDROXYUREA BETWEEN THE TWO
GROUPS.
ALSO WE LOOKED AT THE BONE
MARROW DENSITY THE P VALUE WAS
207 THOUGH IT WAS NOT
STATISTICALLY SIGNIFICANT BUT
GIVEN THE SAMPLE SIZE THAT MAY
BE SAYING SOMETHING.
THIS IS THE CONTINUATION OF THE
RESULT AND THE TABLE WE LOOKED
AT THE UTILIZATION AND DISEASE
BURDEN.
THE NUMBER OF E.D. VISITS AND
HOSPITALIZATION WAS HIGHER IN
PATIENTS WITH AVASCULAR NECROSIS
COMPARED TO PATIENTS WITH NO
AVASCULAR NECROSIS WHILE AGAIN
WAS NOT STATISTICALLY
SIGNIFICANT.
WE USE THE MEASURE TO MEASURE
THE HEALTH RELATED QUALITY OF
LIFE AND THIS IS LIKE A SCALE
BETWEEN 0 TO 100.
THE HIGHER NUMBER MEANING A
BETTER HEALTH RELATED QUALITY OF
LIFE AND IT IS OBVIOUS THAT THE
QUALITY OF LIFE WAS BETTER IN
PATIENT WITH NO AVASCULAR
NECROSIS AND PATIENTS WITH
AVASCULAR NECROSIS LIKE WERE
IMPACTED IN THE FOUR ARMS OF THE
PHYSICAL, EMOTIONAL AND THE PAIN
IMPACT WAS STATISTICALLY
SIGNIFICANT EVEN IN THE SMALL
SAMPLE SIZE BUT THERE WAS NO
DIFFERENCE IN ANXIETY AND
DEPRESSION BETWEEN THE TWO
GROUPS.
SO THIS IS THE INITIAL GRAPH WE
HAD.
IT WAS NOT SURPRISING THE
AVASCULAR NECROSIS WAS MORE
PREVALENT IN OLDER CHILDREN
BETWEEN AGE 11 AND 16.
BUT WHAT WAS SURPRISING TO US IS
WE HAD EIGHT PATIENTS YOUNGER
THAN 10 YEARS OLD AND ONE
PATIENT PRESENTED WAS 4 YEARS
OLD AND HAD AVASCULAR NECROSIS
OF THE FEMORAL HEAD.
COMPARED TO PATIENTS WITH
AVASCULAR NECROSIS OF THE
FEMORAL HEAD PATIENT WITH
AVASCULAR NECROSIS HAD
SIGNIFICANTLY BETTER QUALITY OF
LIFE DUE TO PAIN AND ABOUT 24%
OF THE PATIENT WERE LESS THAN 10
YEARS OLD.
WE FOUND NO DIFFERENCE IN
HYDROXYUREA USAGE AND BONE
MINERAL DENSITY.
MORE DATA IS COMING IN.
CURRENTLY WE'RE DOING IN
PROGRESS BY STUDYING THE GENETIC
DATA AND GETTING DATA FROM THE
DEPARTMENT OF HEALTH FROM
TENNESSEE TO COMPARE AND DATA
LIKE RECENT DATA BEFORE THE
PRESENTATION THERE WAS 83
PATIENTS MORE RECENTLY ENROLLED.
SO THIS IS THE OUTCOME OF THE
SURGICAL INTERVENTION IN THE
COHORT.
THE MOST RECENT NUMBER IS 151
PATIENT AND 65 OF THEM HAD
AVASCULAR NECROSIS.
86 DID NOT HAVE.
OUT OF THE 65 ABOUT 20 HAD CORE
DECOMPRESSION AND 15 OF THEM HAD
IT WITHIN ONE YEAR OF THE
DIAGNOSIS.
AND FIVE HAD IT BETWEEN 14
MONTHS TO 6 1/2 YEARS.
SIX HAD ARTHROPLASTY.
WE HAVE THE SAMPLE SIZE AND ONLY
INCLUDED PATIENT WITH MRI WITH
SUSPECTED AVASCULAR NECROSIS BUT
HAVE NOT LOOKED AT THE PATIENT
WHO WERE LIKE DID NOT HAVE HIP
PAIN.
WE COULDN'T JUST SAFELY ASSUME
ALL THE PATIENTS DID NOT HAVE
AVASCULAR NECROSIS.
THAT'S ONE OF THE LIMITATIONS OF
THE STUDY.
WE DID THE SCREENING IN SICKLE
CELL ABOUT SIX BUT NO ROUTINE
SCREENING FOR AVASCULAR
NECROSIS.
SO THE CONCEPT OF THE SCREENING
IS TO CREATE GUIDELINES FOR
SURVEILLANCE AND IT SHOWED IN
YOUNGER PATIENTS AND RESEARCH
HAS SHOWN THAT AVASCULAR
NECROSIS SICKLE CELL CAN BE AN
INDEPENDENT RISK FACTOR OF
AVASCULAR NECROSIS.
SO THE BENEFIT IS TO PREVENT
COMPLICATIONS AND START EARLY
TREATMENT AND THERE'S RESEARCH
SHOWING THIS ACTUALLY IS MORE
BENEFICIAL TO THE PATIENT THAN
WAITING UNTIL THE COLLAPSE OF
THE HIP.
SO THE LIMITATION OF THE
SCREENING IS LIKE FIRST OF ALL
IT'S NOT THE GUIDELINE.
THE COST OF THE SCREENING AND
OBTAINING MRI AND LACK OF
EVIDENCE OF EFFICACY OF
INTERVENTION IN EARLY STAGES OF
AVASCULAR NECROSIS AND
COMPLICATIONS OF SURGERY.
THIS IS A STUDY THAT IT IS
BETTER TO DO SCREENING AND
BETTER TO INTERVENE EARLY IN THE
EARLY STAGE OF THE DISEASE.
WHAT IS THE FUTURE HOLD?
WE NEED TO EXPAND RESEARCH AND
USE NATIONAL REGISTRIES SUCH AS
GRAND DAD TO GET MORE DATA.
WE NEED TO STUDY THE
EFFECTIVENESS OF INTERVENTIONS.
I KNOW THERE WAS DEBATE IN
YOUNGER PATIENTS BUT WHERE HE
NEED TO EXAM THE RATIONALE OF
DOING MRI AND INVESTIGATE THE
CURATIVE THERAPIES DISCUSSED IN
THE FIRST DAY TO REVERSE THE
PROGRESSION OF THE DISEASE.
I WANT TO THANK THE ENTIRE TEAM
AT ST. JUDE.
IT TAKES A VILLAGE AND THANK YOU
TO NHLBI FOR THE OPPORTUNITY.
>> ANY QUICK QUESTIONS FROM THE
AUDIENCE?
ONE QUICK QUESTION.
>> NICE PRESENTATION.
THERE ARE REPORTS FROM INDIA
WHERE THEY'RE OBSERVING AVN
FREQUENTLY IN A CERTAIN PART OF
THE COUNTRY WHERE THEY'VE DONE
IMAGING AND EVERYTHING AS YOUNG
AS 6 YEARS OLD IN LARGE NUMBERS.
THEY DON'T HAVE THE PERCENT BUT
IT'S MORE RECENT INFORMATION.
THE OTHER QUESTION IS DO THESE
PHOSPHONATES REDUCE PAIN?
>> THE FIRST QUESTION WE'RE
SEEING THAT ALSO IN ST. JUDE.
THERE WAS A SURPRISE TO HAVE
AVASCULAR NECROSIS AT THE YOUNG
AGE.
THE PATIENT STARTED HYDROXYUREA
EARLY AND WE'RE LEANING TO CHECK
IN FOR GENETIC RISK FACTORS ON
THE PATIENTS.
THERE'S PAPERS PHOSPHONATE HELPS
WITH PAIN AND STOPS REGRESSION
AND REVERSE.
BECAUSE OF THE SIDE EFFECTS I
SPOKE TO MANY SENIORS AT
ST. JUDE, BECAUSE OF THE SIDE
EFFECT OF THE PHOSPHONATE IN
CHILDREN THEY'RE NOT FOR USING
IT.
WE NEED MORE RESEARCH TO SEE THE
EFFECT MAYBE SOME CLINICAL TRIAL
TO BE ABLE TO ASSESS THE SAFETY
IN CHILDREN BUT YES, IT DOES
HELP WITH PAIN IN THE OPTION.
>> THANK YOU AGAIN.
LET'S MOVE ON TO THE NEXT
TALK -- IS THERE SOMETHING
ONLINE?
DR. ELBASHIR CAN ADDRESS THAT
ONLINE IN YOUR LAPTOP.
SORRY, WE'RE OUT OF TIME.
LET'S MOVE ON TO THE NEXT TALK
WHICH IS DISSEMINATION AND
TRUST, GENE THERAPY INFORMATION
CAMPAIGN BY SCDAA, DR. LEWIS
HSU.
>> GOOD MORNING.
I WANT TO MENTION THAT I WAS
AFFILIATED WITH CDC IN THE
PROGRAM BUT NOT REALLY
AFFILIATED CDC.
THIS IS ABOUT SICKLE CELL
DISEASE ASSOCIATION OF AMERICA
AND I'D LIKE TO FIRST
ACKNOWLEDGE MY PARTNERS, DR. IVY
IN THE AUDIENCE.
AND DR. HARTFIELD.
I'M A VOLUNTEER CHIEF MEDICAL
OFFICER.
THE MISSION OF SCDAA IS TO
ADVOCATE FOR PEOPLE AFFECTED BY
SICKLE CELL CONDITIONS AND
MAXIMIZE QUALITY OF LIFE AND
ADVANCE THE SEARCH FOR UNIVERSAL
CURE.
THE STRUCTURE IS THERE'S MEMBER
ORGANIZATIONS OVER 50 ACROSS THE
COUNTRY.
THE DISTRIBUTION OF THE MEMBER
ORGANIZATIONS MORE OR LESS
REFLECTS SICKLE CELL DISEASE AND
WHERE THERE'S STATES WITH NOT
THIS ORGANIZATION REFLECT MORE
WORK TO BE DONE.
THE MEMBER CATEGORIES ARE
INDIFFERENT TIERS.
SOME ARE DOING ADVOCACY, SOME
ARE DOING SUPPORT IN ADDITION
AND DIRECT SERVICE TO THE MEMBER
INDIVIDUALS WITH SICKLE CELL
DISEASE.
AND COVID IS SPIKING AGAIN AND
PEOPLE WITH SICKLE CELL DISEASE
OFTEN WERE NOT ABLE TO STAY AWAY
FROM THE HOSPITAL AND STAY IN
ISOLATION BECAUSE OF THE OTHER
THINGS GOING ON WITH SICKLE CELL
DISEASE.
THE QUESTION WAS WERE PEOPLE
WITH SICKLE CELL AT RISK AND
THIS BECAME A REAL OPPORTUNITY
AND RESPONSIBILITY FOR SCDAA AND
THE MEDICAL AND RESEARCH
ADVISORY COMMITTEE THAT RAMPED
UP FROM MEETING ONCE A YEAR TO
ONCE A WEEK AND TRYING TO LEARN
FROM AN EFFORT IN COMMUNITY
ENGAGEMENT UNLIKE ANYTHING SCDAA
HAD DONE BEFORE.
THROUGH THIS WE WERE ALSO
PREPARING TOOLS FOR WHAT WE KNEW
WAS COMING WHICH IS GENE THERAPY
ANNOUNCEMENTS AND GENE THERAPY
WITH GOOD NEWS AND BAD NEWS WAS
CAUSING CONFUSION AND EXCITEMENT
AND PEOPLE NEEDED TO KNOW
INFORMATION.
ANOTHER CONTEXT FOR THOSE
INCLINED THE NASEM REPORT THE
NATIONAL AQUAKED -- ACADEMY AND
MEDICINE CALLED A BLUEPRINT
SAYING WHAT WERE NEEDED WERE
SHOWN IN THE PILLARS AND E AND F
WERE ABOUT AWARENESS AND
ADDRESSING BARRIERS TO ACCESS.
FINALLY THERE'S A GENERAL
CONTEXT THERE'S A RISE IN
AWARENESS OF DISSEMINATION AND
IMPLEMENTATION SCIENCE FOR COVID
VACCINES THIS BECAME IMPORTANT
WITH STATEMENTS SUCH AS FROM
THIS FAMOUS BALTIMORE PASTOR A
MINISTER AND MASTER OF PUBLIC
HEALTH AND PREVIOUSLY A FEDERAL
HEALTH OFFICIAL SAYING THAT WHEN
YOU'RE TALKING ABOUT STUFF FOR
SOMEBODY'S HEALTH FOR THE
MINORITY POPULATION YOU CAN'T
JUST DO HERE'S WHAT WE'RE GOING
TO DO TO YOU AND HELP YOU.
HE SAID THAT'S WAY TOO
PATERNALISTIC AND HARMFUL
THROUGH THE YEARS AND IS NOT
GOING TO ADD TO THE SPREAD OF
INFORMATION SO MUCH AS IT'S
GOING TO ADD TO DISTRUST.
AND SO THAT'S A QUOTE FROM
PASTURE TERRENCE KING IN
BALTIMORE.
AND ONE OF THE THINGS HE WOULD
DO IS AS A MINISTER TOO HE WOULD
COUCH THINGS IN THE SETTING OF
FAITH-BASED MESSAGES FOR HIS
CONGREGATION AND SAY NOT
EVERYTHING THAT COMES AS
SALVATION -- NOT EVERYTHING THAT
KWO
COMES TO HELP YOU AND EVEN IN
THE CASE OF MOSES OR NOAH AS A
MAN OF GOD THEY WEREN'T JUST
WAITING FOR GOD TO DO SOMETHING
THEY HAD TO DO SOMETHING AND FOR
NOAH HE DIDN'T SAVE HIS FAMILY
JUST BY PRAYING, HE HAD TO
PHYSICALLY BUILD AN ARK AND HE
HAD TO DO A LITTLE EXPERIMENT
AND HAD TO SEND OUT BIRDS TO SEE
IF THEY LANDED ON DRY LAND OR IF
THEY COULDN'T FIND DRY LAND AND
COME BACK SO HIS EXPERIMENT
RECORDED IN THE BIBLE IS PART OF
THIS CREDIT TO HIM AS BEING A
MAN OF FAITH.
PASTOR KING WAS GIVING AN
EXAMPLE TO HIS CONGREGATION
SOMETIMES YOU HAVE TO USE HUMAN
TOOLS TO BE ABLE TO MANIFEST
YOUR FAITH.
DISSEMINATION EXPERIENCES DURING
THE COVID PANDEMIC BUILT IDEAS
OF TRUSTED MESSENGERS, COMMUNITY
PARTNERSHIP AND TRYING TO
ADDRESS RACIAL AND ETHNIC
DISPARITIES AS WELL AS ADDRESS
THE PARENTS AND CAREGIVERS WHILE
DOING ALL THIS STUFF.
SO THESE WERE SOME OF THE TOOLS
FROM DISSEMINATION,
IMPLEMENTATION SCIENCE THAT
SCDAA WAS TRYING TO BUILD IN.
AND OVER ALL DISSEMINATION
SCIENCE IS A YOUNGER FIELD THAN
IMPLEMENTATION SCIENCE SHOWN BY
THE ICON OF A BUDDING SEED.
BUT THERE ARE WAYS TO DO AN
ACTIVE AND PLANNED SPREAD OF
EVIDENCE-BASED INFORMATION WITH
DIFFERENT FRAMEWORKS AS SHOWN
HERE IN THIS REFERENCE.
AND THE ONE WE WERE CHOOSING FOR
SCDAA WAS THIS IDEA OF TRUSTED
MESSENGERS BUT ALSO USING
SEVERAL FORMATS.
DIFFERENT MEDIA PATHWAYS.
SOME WAS COMMUNITY LEADERS,
PEERS AND ALSO LOOKING TO THE
GATE KEEPERS OF A COMMUNITY.
AT THE SAME TIME LOOKING AT MASS
MEDIA, LOCAL MEDIA, ETHNIC
MEDIA, SOCIAL MEDIA AND MEMBER
ORGANIZATIONS AS WE WERE SEEING
ARE LOCALLY PLACED AND HAVE TIES
TO WHAT'S GOING TO ON WITH THEIR
STATE OR THEIR COUNTY OR PARISH.
AND A KEY IDEA IN THIS IS TO
LISTEN TO THE PEOPLE, SEE WHAT
THEY WANT TO KNOW, ANSWER THOSE
QUESTIONS, LISTEN TO THEM AGAIN
TO FIND OUT WHAT THEY ARE WANT
TO KNOW NEXT AND THEREFORE YOU
BECOME TRUSTED BECAUSE YOU'RE
ANSWERING PEOPLE'S QUESTIONS
OPPOSED TO GIVING ANNOUNCEMENTS
TO THINGS PEOPLE DIDN'T REALLY
WANT TO KNOW OR WHAT THEY WANTED
TO KNOW YOU NEVER ANSWERED.
SO THIS BECAME OUR STRATEGY
THROUGH COVID AND THIS BECAME
THE GENERAL DISSEMINATION
STRATEGY WAS A CONTINUOUS
FEEDBACK LOOP OF LISTENING TO
WHAT WAS HAPPENING THROUGH THE
COMMUNITY-BASED ORGANIZATIONS
THROUGH THE MEMBER ORGANIZATIONS
AS WELL AS THROUGH WHAT WE'RE
HEARING FROM DIFFERENT
PROVIDERS.
SOME THINGS WOULD BE GENERATED
SUCH AS THIS A STATEMENT ABOUT
THE CLINICAL TRIAL PAUSE IN ONE
OF THE GENE THERAPY STUDIES DUE
TO CASES OF ACUTE MYELOCIDIC
LIEUKEMIA AND TRYING TO ADDRESS
THE CONCERN WITH FREQUENTLY
ASKED QUESTIONS FORMAT AS WELL
AS RECOMMENDATIONS.
I WANT TO ACKNOWLEDGE SEVERAL
MEMBERS OF MARAC ARE HERE IN THE
AUDIENCE.
THANK YOU VERY MUCH.
AND HOW CAN WE THE MEMBER
ORGANIZATIONS AND USE THE
DIFFERENT FORMATS.
AND USED THAT TO TALK ABOUT GENE
THERAPY IN A CONCERTED WAY.
WITH THREE GENE THERAPY MASTER
CLASSES TALKING ABOUT WHAT SORTS
OF ISSUES THERE WERE IN DETAIL
WITH OPPORTUNITIES FOR THE
MEMBER ORGANIZATIONS AND THE
AUDIENCE TO ASK QUESTIONS.
THERE WAS DURING THE CONVENTION,
ANNUAL CONVENTION OF SCDAA IN
OCTOBER SESSIONS ON GENE THERAPY
WITH MORE OPPORTUNITIES TO ASK
QUESTIONS AND MORE INTERACTIONS
AND SCDAA CONTINUED ON WITH
DISCUSSION OF THE REPORT ON GENE
THERAPY THAT TALKED ABOUT COST
EFFECTIVENESS.
AS THIS WAS GOING ON, THERE WAS
MORE AND MORE INTERACTION WITH
MEDIA.
MEDIA STARTED COMING TO US
ASKING FOR INTERVIEWS AND CBOs
WERE ASKING FOR MORE WEBINARS.
THERE WAS STARTING TO BE DEMAND
AND PROVIDERS WERE ASKING AND
EXPECTING PATIENTS.
A SMALL BALL EFFECT WAS
HAPPENING.
BY THE TIME THE ANNOUNCEMENT OF
FDA APPROVAL WE WERE MOSTLY
READY DECEMBER 8 EXCEPT WE WERE
READY FOR ONE TO BE APPROVED AND
FDA APPROVED TWO.
WE HAD TO SIT IN THE HALLWAYS OF
THE ASH MEETING RETYPING SOME OF
THE STATEMENTS THAT WERE
PREPARED FOR RELEASE AND REWORD
THEM ABOUT TWO GENE THERAPIES.
THIS WAS FOLLOWED BY A STATEMENT
IN THE AFTERNOON LIKE FDA
ANNOUNCEMENT AT 9:00 OR 10:00 IN
THE MORNING.
IF ANYBODY WANTS TO SEE THAT
STATEMENT IT'S STILL ONLINE.
SPECIFICALLY WE HAD A WARRIOR
FAQ.
SICKLE CELL DISEASE WARRIORS HAD
SPECIFIC QUESTIONS.
WE TRIED TO CONDENSE THESE TO
UNWUN
CONDENSE THESE USED BY
COMMUNITY-BASED ORGANIZATIONS TO
TRY TO ADDRESS WHAT PEOPLE
WANTED TO KNOW.
I'LL SKIP THIS IN THE INTEREST
OF TIME.
EVERYONE KNOWS COST IS A BIG
ISSUE.
HERE'S THE STATISTICS OF WHAT
KINDS OF THINGS WERE SHOWN AS
THE IMPACT MUCH THIS
DISSEMINATION CAMPAIGN.
I'LL SAY THE SICKLE CELL DISEASE
ASSOCIATION CONTRACTS WITH THE
BONIE HENESON GROUP AND WE THANK
YOU VERY MUCH.
SO MEDIA OUTREACH, THERE WAS A
LOT OF MEDIA APPEARANCES.
I'M NOT PHOTO GENIC.
I'D RATHER DO RADIO THAN TV BUT
HAVE TO DO TV AND RADIO AND GOT
TO DO BLOGS AND GOT TO DO
PODCASTS, ALL KINDS OF STUFF
WITH OUTLETS THAT NORMALLY DON'T
SEEM TO PAY ATTENTION TO SICKLE
CELL SUCH AS BLOOMBERG AND FOX
NEWS AND NPR.
I TRIED TO DO PITHY STATEMENTS.
MY PARTNERS ALSO HAD PITHY
STATEMENTS.
THEY WERE MEDIA FRIENDLY.
WE TRIED TO GET THE WORD OUT A
LOT AND 360 IS A LOT OF MEDIA
APPEARANCES.
SOME CAME OUT IN PRINT AND 400
MILLION PEOPLE WERE PROBABLY
REACHED AND THIS IS SOCIAL MEDIA
IN DIFFERENT OUTLETS YOU SEE THE
NUMBERS WE'RE REACHING THROUGH
FACEBOOK AND X FORMERLY TWITTER
AND SOCIAL MEDIA IMPRESSIONS.
AS WELL AS WEBSITE ENGAGEMENT
WITH THOUSANDS OF VIEWS, E-MAIL
LETTERS, E-MAIL NEWSLETTER
COMING OUT WEEKLY WITH 10,000
AND MASTER CLASSES WHICH
CONTINUED ON TO 2024 WITH 310
ATTENDEES ON A MASTER CLASS
ONLINE LIVE AND ANOTHER 1,000
AFTERWARDS.
>> TWO MINUTES.
>> OKAY.
NEXT STEPS ARE TO TRY TO
CONTINUE THE WORK WITH
COLLABORATION WITH THE
DEMOCRATIZING WITH GENE THERAPY
EDUCATION AND WE'RE PLEASED AT
THE EFFORTS GOING ON THERE
TRYING TO BRING MORE COMMUNITY
LINKAGE THERE.
EDUCATING HEALTH CARE PROVIDERS
BECAUSE WE'RE STARTING TO HEAR
SOME OF THE COMMUNITY-BASED
ORGANIZATIONS AND PATIENTS ARE
BETTER INFORMED THAN THEIR
DOCTORS ARE.
THERE'S CONTINUED MASTER
CLASSES.
I'LL PUT IN A PLUG FOR THE NEXT
SCDAA ANNUAL CONVENTION IN
OCTOBER IN ATLANTA AND THERE'LL
BE MASTER CLASS THERE TOO.
THAT IS IT.
I'LL BE HAPPY TO TAKE QUESTIONS.
>> GREG COTTO.
LEWIS, WONDERFUL PERSPECTIVE AND
THANK YOU FOR THE REPRESENTATION
OF THE SICKLE CELL COMMUNITY TO
THE POPULAR MEDIA.
ONE OF THE IMMEDIATE
CONSEQUENCES OF SUCH A MEDIA
BLITZ ABOUT GENE THERAPY FOR
SICKLE CELL DISEASE WAS
POTENTIAL IMPRESSION TO ROLL
BACK FUNDING FOR INVESTIGATING
OTHER THERAPIES FOR SICKLE CELL
DISEASE.
I JUST WONDERED IF YOU HAD
IMPRESSION OR FEEDBACK FROM THAT
KIND OF THING BECAUSE THERE WERE
SO MANY TAKEN BY THE MESSAGE
THAT WE DON'T NEED TREATMENT FOR
SICKLE CELL DISEASE ANYMORE.
EVERYBODY'S GOING TO BE CURED.
>> EXACTLY.
THANK YOU FOR THAT COMMENT.
WHEN YOU DO A SINGLE SOUND BITE
THE SECOND POINT GETS LOST BUT
TRY TO PUSH THE IDEA WHILE
GETTING READY FOR GENE THERAPY
YOU HAVE TO STAY IN GOOD SHAPE.
WHILE GETTING READY FOR GENE
THERAPY, PEOPLE NEED TO BE
PROTECTING THEIR ORGANS AND NEED
TO HAVE GOOD HEALTH CARE
SYSTEMS, EMERGENCY DEPARTMENTS,
EVERYTHING ELSE.
THERE'S A STRONG MESSAGE IN
THERE WE TRY NOT TO GET IT LOST
IN THE HUBBUB.
ALSO, POST GENE THERAPY PEOPLE
NEED FOLLOW-UP AND IF IT FAILS
FOR SOME REASON YOU STILL NEED
SICKLE CELL CARE.
>> THANKS, LEWIS.
FANTAS
FANTASTIC.
RIMAS FROM CARING CROSS.
THE THEME WAS IT'S EASIER TO
PRE-BUNK THAN DEBUNK SO I WANT
TO THANK YOU AND APPLAUD YOUR
ORGANIZATION WHETHER IT'S
COVID-19 OR CELL THERAPIES TO
KEEP THE MESSAGE GOING FORWARD.
HOW DO YOU SEE A SUSTAINABLE
PRO-SCIENCE MESSAGE COMING?
>> WORKING HARD.
CONTINUE TO TRY.
IT'S FABULOUS WORKING WITH
COMMUNITY-BASED ORGANIZATIONS, I
HAVE TO SAY THAT COMPARED TO
EARLIER PARTS OF MY CAREER AS AN
M.D. Ph.D. SITTING IN MY LAB FOR
WEEKS AT A TIME IT'S BEEN SO
DIFFERENT AND SO INTERESTING.
>> I WANT TO ADD THAT AS PART OF
OUR EDUCATION AND MESSAGING WE
HAVE TWO NEW TREATMENTS AND WE
UNDERSTAND THE WAY THINGS GO AND
EXPECT TO HAVE MORE AND ALSO
ENOUGH HAVING DISCUSSIONS ABOUT
WHAT'S HAPPENING IN THE
REGENERATIVE SPACE.
SO I KNOW WE GET A CURATIVE
TREATMENT AND HAVE DAMAGE IN THE
BODY.
WHO IS WORKING ON THAT TO FIX
THAT.
THAT'S ALSO BEEN PART OF OUR
EDUCATION AND MESSAGING.
AS WELL AS SAYING WE UNDERSTAND
THIS IS REALLY BIG BUT WE ARE
THE FIRST AND THERE ARE MANY
OTHER DISEASES TO FOLLOW AND SO
WHAT WE'RE HOPING TO DO IS
EVERYBODY HEARS THAT AND GET A
ROAR NOT ONLY FOR SICKLE BUT WE
CAN START GETTING OTHER DISEASES
FOR US NOT TO BE SILOED.
WE'RE JUST FIRST AND I THINK OUR
COMMUNITY HAS DONE A GREAT JOB
OF SAYING THAT, RESPECTING THAT
MESSAGE AND THAT IMPORTANCE OF
THAT AND GETTING THE MESSAGE
OUT.
>> THANK YOU.
ONLINE?
>> YES, FROM FRANCINE BAKER.
THANK YOU DR. HSU FOR ALL YOU DO
ON BEHALF OF THE SICKLE CELL
COMMUNITY AND THERE WILL BE
INDIVIDUALS WHO NEVER GET GENE
CELL THERAPY.
WE SHOULD NOT FORGET ABOUT THOSE
WARRI
WARRIORS.
>> INDEED.
THANK YOU.
>> THANK YOU, AGAIN.
>> OKAY.
SO WE'RE GOING TO BREAK FOR
ANOTHER 10 MINUTES OR SO.
LET'S GET BACK AT 10:50 HERE
PROMPTLY AND WE'LL START WITH
THE NEXT TALKS.
>> OKAY.
IF WE CAN HAVE OUR SEATS BACK.
WE'RE GOING TO START OUR NEXT
TA
TALK.
WE'LL START WITH OUR NEXT TALK,
EMERGING SICKLE CELL DISEASE
MODIFYING THERAPIES.
DR. MODUPE IDOWU.
GO AHEAD, PLEASE START.
>> I THANK THE ORGANIZERS FOR
THIS PROGRAM AND INVITING ME TO
PRESENT TODAY AND MY TOPIC TODAY
IS EMERGING SICKLE CELL DISEASE
MODIFYING THERAPIES.
THESE ARE MY DISCLOSURES.
SICKLE CELL DISEASE IS A SEVERE,
CHRONIC HEMOLYTIC CONDITION BY
ORGAN DYSFUNCTION PUNCTUATED
WITH ACUTE EVENTS AND VASO
OCCLUSIVE PHENOTYPE AND ANEMIC
PHENOTYPE AND THERE'S LOW NITRIC
OXIDE AND AS SEEN ON THE DIAGRAM
LEADING TO COMPLICATIONS CAUSED
BY VASCULOPATHY AND STROKE.
THE PATIENTS HAVE MULTIORGAN
FAILURE EASILY EVEN WHEN THEY
DON'T COME IN WITH VASO
OCCLUSIVE CRISES AS THOSE THAT
HAVE THE PHENOTYPE AS SEEN ON
THE RIGHT OF THE DIAGRAM.
THOUGH SOME ARE RIGHT IN THE
MIDDLE AND HAVE BOTH PHENOTYPES.
6:
THE CHOICE OF THERAPIES DEPENDS
ON THE COMPLICATIONS.
WHAT I MEANT IS THE HEMOLYTIC
HAVE THE LOW NITRIC OXIDE
LEADING TO DYSFUNCTION AND VASO
OCCLUSIVE ONES HAVE HIGH LEVELS
OF LEUKOCYTE COUNTS AND HIGH
HEMOGLOBIN LEVELS AND
COMPLICATIONS BECAUSE OF
OBSTRUCTION OF CAPILLARIES BY
ERYTHROCYTES AND HAVE THE
COMPLICATIONS AS ACUTE CHEST
SYNDROME AND AVN AND ACUTE PAIN
SYNDROMES.
THERE ARE MULTIPLE BIOLOGICAL
TARGETS.
THOSE HIGHLIGHTED IN BLUE FDA
APPROVED AND YOU CAN SEE WE CAN
TARGET ANYWHERE FROM THE DNA AND
PROTEINS AND CELLULAR LEVEL AND
CAN ALSO TARGET THE VASCULAR AND
DO THE VASCULAR PLASMA AND END
ORGAN.
I WILL TALK MORE ABOUT TARGETING
ON THE CELLULAR LEVEL AND USING
THE AFFINITY BINDING TYPE OF
THERAPIES.
THERE ARE MANY SICKLE CELL
DISEASE CLINICAL COMPLICATIONS
DIVIDED INTO ACUTE AND CHRONIC
COMPLICATIONS.
WE SHOULD ALSO NOTE THAT SOME OF
THE THERAPIES ONLY EFFECT SOME
OF THE COMPLICATIONS BUT AS LONG
AS THEY ARE EFFECTIVE FOR TWO OR
MORE OF THESE OR ONE OR MORE OF
THE COMPLICATIONS, THEN WE
SHOULD BE ABLE TO USE THEM IN
CLINICAL PRACTICE.
AS WE DEVELOP NEW THERAPIES WE
SHOULD FIND OUT WHICH ONES ARE
GOOD FOR EACH OF THE
COMPLICATIONS.
THESE ARE THE FDA APPROVED
THERAPIES.
HYDROXYUREA, L GLUTAMINE AND
CRIZANLIZUMAB IS GOOD FOR
PRIAPISM AND IT DEPENDS ON THE
PHENOTYPE THE PATIENT IS
EXHIBITING AND THESE ARE THE
EXAMPLES HOW TO USE THE FDA
APPROVED THERAPIES FOR ALL
PATIENTS 9 MONTHS AND OLDER THEY
SHOULD BE PROBABLY OFFERED
HYDROXYUREA IF WE WANT TO LIMIT
TRANSFUSION WE WANT TO KEEP THE
HEMOGLOBIN IN A HIGH STEADY
STATE THEN WE NEED TO CONSIDER
USING KRIZ -- THE MEDICINE AND
THERE'S BEEN CASE HISTORIES OF
PATIENTS DOING BETTER ON
VOXELOTOR AND HYDROXYUREA.
PED AND THIS PATIENT PRESENTED
WITH NORMAL LEVEL OF T195 AND
CREATINE 0.4 AND COULD NOT
TOLERATE HYDROXYUREA AND
INTERESTED IN NEWER TARGETED
THERAPIES THAT CAN IMPROVE HER
HEMOGLOBIN AND ENERGY LEVEL.
A HEMATOLOGIST DISCUSSED
PYRUVATE KINASE ACTIVATORS AND
GBT601 TO HER.
SO NOW I'LL TALK ABOUT THE
EMERGING INVESTIGATIONAL
PHARMACOLOGIC THERAPIES FOR
SICKLE CELL DISEASE.
I APOLOGIZE MY SLIDES ARE NOT
PROJECTING WELL WHEN THEY
TRANSITIONED.
THEY WERE ANOTHER COLOR
ACTUALLY.
THE DIRECT HEMOGLOBIN AS
POLYMERIZATION INHIBITOR AND
PYRUVATE KINASE ACTIVATORS AND
THE THERAPIES THAT INDUCE
HEMOGLOBIN F ARE MENTIONED IN
SITU AND ADDRESS CELL ADHESIONS
AND AND THERE'S AN INHIBITOR
WITH A HIGHER AMOUNT THAN
VOXELOTOR.
IT COULD IMPROVE CLINICAL
OUTCOME THERE'S A STUDY TO
EVALUATE THE EFFECT OF
OSIVELOTOR TREATMENT AND
IMPROVEMENTS WERE SEEN TO WEEK
12 ON THE STUDY.
THE MEAN HEMOGLOBIN INCREASE IN
THE 100 MILLIGRAM GROUP OF
OSIVELOTOR WAS IMPROVED AND ONE
MILLIGRAM GROUP WAS 1.317.
THIS SLIDE BASICALLY SHOWED THE
IMPROVEMENT IN HEMOGLOBIN.
AND HEMOLYSIS WAS OBSERVED AT
WEEK 6 AND 12.
AND THE INDICATORS OF OXYGEN
SUGGESTED NO IMPAIRMENT AND NO
INCREASE IN EQUAL LEVELS OF VOC
AND IMPROVED IN HEMOGLOBIN S
POLYMERIZATION.
OSIVELOTOR HAS GONE TO PHASE III
STUDY AT THIS POINT.
NOW I'LL MOVE TO PYRUVATE KINASE
ACTIVATOR.
IT'S A KEY ENZYME IN RBC
METABOLISM AND PRODUCTION OF
ATP.
IN OUR PATIENT WITH SICKLE CELL
DISEASE, STABILITY ARE REDUCED
COMPARED TO HEALTHY CONTROLS.
AND THIS DIAGRAM SHOWED THE PK
ACTIVATORS HAVE THE POTENTIAL OF
HAVING A DUAL MECHANISM OF
INCREASING ATP AND 1 AND 3DPG
AND INCREASE THE ENERGY AND
HEMOGLOBIN AFFINITY THERE BE
REDUCING HEMOGLOBIN
POLYMERIZATION.
THE AGENCY UNDER INVESTIGATION
INCLUDE MITAPIVAT AND AG946.
THIS WAS PRESENT THE RISE OF
PHASE 2 RESULTS IN DECEMBER OF
2023.
MITAPIVAT IS A FIRST-IN CLASS
ORAL SMALL MOLECULE UNDER
INVESTIGATION FOR THE TREATMENT
OF SICKLE CELL DISEASE.
THIS HAS BEEN APPROVED IN THE
U.S. FOR HEMOLYTIC ANEMIA AND PK
DEFICIENCY IN E.U. AND U.K. FOR
TREATMENT OF THESE PATIENTS.
SO IN THE RISE UP STUDY WE FOUND
THERE WAS DOSE DEPENDENT
DECREASE IN 2,3DPG LEVELS AND 42
PRIMARY EFFICACY END POINT WE
FOUND OUT THAT 46.2% OF PATIENTS
IN THE 50 MILLIGRAM ON AND 50%
OF PATIENTS IN THE OTHER ARM HAD
INCREASE IN HEMOGLOBIN COMPARED
TO THE PLACEBO GROUP AND THE
INCREASE IN THE 50 MILLIGRAM WAS
1.11 GRAM PER DECILITER AND THE
DIFFERENCES RESPECTIVELY
COMPARED TO 1.71 IN THE PLACEBO
GROUP.
THIS DIAGRAM SHOWS THE SAME
INFORMATION I JUST PRESENTED.
THIS IS THE SAME INFORMATION
GIVEN THAT THERE WAS A REDUCTION
IN ANALYZED RATE OF SICKLE CELL
PAIN CRISIS AND MITAPIVAT WAS
CONSISTENT WITH PREVIOUSLY
REPORTED DATA IN SAFETY AND RISE
UP IS NOW IN PHASE 3.
WE ALSO PUBLISHED A PHASE 1
STUDY OF OVE TAVOPIVA IN BLOOD
ADVANCES AND IN THE PHASE 1
STUDY 36 WERE ENROLLED IN FOUR
COHORTS FOR THE ETAPIVAT AND
THEY RECEIVED IT ONCE DAILY FOR
12 WEEKS AND CONSISTENT WITH THE
MECHANISM OF ACTION THERE WAS
INCREASE IN ATP, DECREASING TO
2,3 DPG AND INCREASE OF ONE GRAM
IN THE HEMOGLOBIN LEVEL IN 73%
OF THE PATIENT DURING TREATMENT
PERIOD AND MARKERS WERE
DECREASED AND IN THIS STUDY OF
ETAPIVAT IN SICKLE CELL DISEASE
ONE MILLIGRAM DAILY FOR 12 WEEKS
WAS WELL TOLERATED AND DECREASED
HEMOLYSIS.
AND BACK TO THE CASE I
PRESENTED.
AND IT IMPROVED TO 9 IN 10 AND
DECREASED SIGNIFICANTLY AND
ENERGY LEVEL IMPROVED.
SHE WAS ABLE TO CONTINUE COLLEGE
UNINTERRUPTED AND HAD GOOD
QUALITY OF LIFE.
I'LL SAY ONE STATEMENT IT'S ALSO
IN CLINICAL TRIAL RIGHT NOW
PHASE 1 AND 2 AND BASICALLY
GIVEN ONCE OR TWICE PER WEEK.
IT'S FOUND TO INDUCE FETAL
HEMOGLOBIN AND SEEMS SAFE SO
FAR.
AND INCLAUMAB TO REDUCE VOC.
THE MODIFYING THERAPIES SHOULD
BE BASED ON PATIENT AND
CAREGIVER PREFERENCES.
WE SHOULD LOOK AT THE ORAL
VERSUS IV AND WHETHER THEY'RE
OPEN TO CLINICAL TRIALS.
THERE'S PSYCHOSOCIAL
CONSIDERATION AND MONITORING AND
ADVERSE EVENTS FROM THERAPY WILL
HELP IMPROVE ADHERENCE AND
IMPROVE OVER ALL TREATMENT
OUTCOME.
AND THIS IS OUR TREATED SICKLE
CELL PATIENTS SAME AS TREATED
EARLIER DEPENDING ON THEIR
PHENOTYPE IF THEY'RE MORE HEMEC
CONSIDERING THERAPIES MORE THAN
OTHERS.
AND TURN TO FDA APPROVED
THERAPIES AND IDEA THE CLINICAL
TRIALS THAT ARE OPEN AT MY SITE.
SO IN CONCLUSION, SICKLE CELL
DISEASE IS A SINGLE GENE
DISORDER WITH A COMPLEX
PHENOTYPIC EXPRESSION.
SICKLE CELL DISEASE IS A
DISABLING CONDITION THAT AFFECT
MULTIPLE ORGAN SYSTEMS.
THERE'S MULTIPLE POTENTIAL
TARGETS IN THE DEVELOPMENT OF
THERAPEUTIC AGENTS DEPENDING ON
SICKLE CELL DISEASE PHENOTYPIC
EXPRESSION AND COMPLICATIONS.
EACH OF THE THERAPIES CAN BE
GIVEN ALONE OR IN COMBINATION
WITH HYDROXYUREA THERAPY.
AND OTHERS ARE UNDER CLINICAL
INVESTIGATION WITH SOME
ENCOURAGING RESULTS.
THANK YOU FOR YOUR ATTENTION.
>> THANK YOU.
SO FOR THE SAKE OF TIME, I THINK
WE'RE GOING TO MOVE ON.
ARE THERE ANY ONLINE QUESTIONS
OR COMMENTS?
NONE.
OKAY, LET'S MOVE ON TO OUR NEXT
TALK BY ZACHARY RAMSAY THE
INFLUENCE OF SEX HORMONES IN
SICKLE CELL PAIN IN WOMEN FROM
CARIBBEAN INSTITUTE OF HEALTH
RESEARCH.
>> WE HAVE NOW FINISHED DATA
COLLECTION.
SO SORRY BUT THESE ARE NOT THE
LATEST SLIDES THAT ARE UPDATED.
IS IT POSSIBILITY TO CHECK BACK
WITH WHAT'S ON THE REPOSITORY?
ALL RIGHT.
I'LL GO AHEAD.
IN OUR PREVIOUS WORK IN JAMAICA
WE HAVE FOUND WOMEN WITH SICKLE
CELL DISEASE ARE NOTED TO HAVE
HIGHER ODDS OF NEUROPATHIC PAIN
AND TO BE MORE SENSITIVE TO
PRESSURE TO PAINFUL STIMULI AND
IN MENSTRUAL STUDIES WE HAVE
FOUND THAT WOMEN WITH SICKLE
CELL DISEASE ARE TO NOTED TO
HAVE VASO OCCLUSIVE PAIN FOUND
TO BE TEMPORARILY ASSOCIATED
WITH THE ONSET OF THEIR MENSES
AND FOUND HORMONAL
CONTRACEPTIVES HAVE BEEN SHOWN
TO INCREASE THE RACE OF VASO
CRISIS.
AND WE FOUND HIGH ESTRADIOL
LEVELS ARE ASSOCIATED WITH
DECREASED PAIN THRESHOLDS AND
PROGESTERONE LEVELS HAVE AFFECT
IN REGULATION OF PAIN IN THE
LUTEAL PHASE.
THESE FINDINGS SUGGEST THERE MAY
BE A NEUROLOGICAL LINK BETWEEN
SEX HORMONES AND SICKLE CELL
DISEASE PAIN AND WANTED TO
INVESTIGATE THAT FURTHER.
NOW, THERE ARE SOME VERY
IMPORTANT CONFOUNDERS WE HAVE TO
CONSIDER WHEN TRYING TO ASSESS
THIS RELATIONSHIP.
FIRSTLY, SLEEP, DEPRESSION AND
ANXIETY ARE KNOWN TO HAVE WELL
ESTABLISHED LINKS BETWEEN SICKLE
CELL DISEASE PAIN AND
SENSITIZATION AS WELL AS TO BE
LINKED WITH SEX HORMONES.
WE COLLECTED THE DATA DURING THE
COVID-19 PANDEMIC AND WE FELT WE
COULD NOT IGNORE THE DATA
BECAUSE BOTH COVID-19 INFECTION
AND THE VACCINES HAVE BEEN
ASSOCIATED WITH ABNORMAL MENSES
AND PERIPHERAL NEUROPATHY.
HYDROXYUREA HAS BENEFITS IN
TERMS OF VASO OCCLUSIVE CRISIS
BUT FOUND TO BE RESULT IN
PERIPHERAL NEUROPATHY WHEN USED
ON PATIENTS WHO DO NOT HAVE
SICKLE CELL DISEASE.
WE HAVE TO CONSIDER DIFFERENT
HEMATOLOGICAL FACTORS AND AFFECT
CELLULAR ADHESION.
SO THE AIM OF THE RESEARCH WAS
TO INVESTIGATE VARIATION LEVELS
OF SEX HORMONES ASSOCIATED WITH
PAIN DETECTION THRESHOLDS AS
MEASURED BY QUANTITATIVE SENSORY
TESTING AMONG WOMEN WITH SICKLE
CELL DISEASE.
AND WE PERFORMED A PROSPECT ITCH
COHORT STUDY IN JAMAICA AND
INCLUDED WOMEN WHO HAD SICKLE
CELL DISEASE WHO WERE 18 YEARS
OR OLDER.
IF THEY HAD REGULAR MENSES AND
INCLUDED THEM IF THEY WERE
PREGNANT AND HAD A HISTORY OF
HYSTERECTOMY AND HAD A CRISIS AT
THE TIME OF THEIR VISIT OR
UNDOCUMENTED COGNITIVE DEFICITS
OR WERE ON CONTRACEPTIVES IN THE
LAST THREE MONTHS.
THESE WERE THE MEASUREMENTS
PERFORMED.
AND THE MEASUREMENTS WERE BASED
ON THE EXPERTS' RECOMMENDED
SCHEDULE TO MINIMIZE THE
VARIABILITY BETWEEN PERSONS.
WE PERFORMED A FOLLICULAR PHASE
VISIT BETWEEN DAY 6 TO 11 OF THE
MENSTRUAL PSYCH AND LUTEAL PHASE
17 TO 21.
WE ASSESSED FOR THE PROBABLE
PRESENCE OF NEUROPATHIC PAIN AND
LOOKED AT THE FREQUENCY AND
SEVERITY OF THE VASO OCCLUSIVE
CRISIS USING THE ASK ME PAIN
EPISODE AND LOOKED AT OTHER
PSYCHOSOCIAL AND CONFOUNDERS AND
PERFORMED QUANTITATIVE SENSORY
TESTING AND THERMAL TESTING AT
THE FOREARM AND LEG AND LOOKED
AT SEX HORMONES AS WELL AS THE
COMPLETE BLOOD COUNT AND
RETICULOSITE COUNT.
WE DID A PREGNANCY TEST AND
LOOKED AT THEIR DEMOGRAPHIC AND
MEDICAL HISTORY AND LOOKED AT
DEPRESSION, ANXIETY AND
DYSMENORRHEA USING VALIDATED
QUESTIONNAIRES.
IN TERMS OF STATISTICAL METHODS
WE HAD LIKELIHOOD ESTIMATION.
THE PRIMARY OUTCOMES WE LOOKED
AT THE MEAN OF THREE TRIALS FOR
PRESSURE PAIN THRESHOLD AND HEAT
PAIN THRESHOLD AT UPPER AND
LOWER LIMB.
WE USED RANDOM INTERCEPTS AT THE
PARTICIPANT LEVEL.
CONSENT USE RANDOM SLOPES
BECAUSE THEY DIDN'T IMPROVE THE
MODELS AND WE ASSESSED
INTERRUPTIONS USING MARGINAL
EFFECTS AND VERY IMPORTANTLY WE
CAPTURED THE TEMPORAL
RELATIONSHIPS OF THE
MEASUREMENTS BY TAKING THE
NUMBER OF DAYS BETWEEN THE
MEASUREMENT AND THE FIRST DAY OF
THEIR LAST MENSES.
WHAT WE DID WAS STANDARDIZED IT
BY VIVDIVIDING IT BY THE LENGTH
THEIR MENSTRUAL CYCLE.
WE DIDN'T HAVE A FORMAL WAY OF
VALIDATING THEY WERE ACTUALLY IN
THE MENSTRUAL CYCLE PHASE WE PER
ASSUMED THEY WERE IN AND
CALCULATED Z SCORES OF HEAT PAIN
THRESHOLD AND NORMATIVE VALUES
OF AFRICAN AMERICAN CYCLES AND
WE LOOKED AT OFF YOU'LLATER
CYCLES.
AND WE INCLUDED 125 AND 103
COMPLETED BOTH VISITS.
THE MEAN AGE WAS 29 YEARS,
APPROXIMATELY 79% OF WOMEN HAD A
SEVERE GENOTYPE.
APPROXIMATELY HALF HAD A
COVID-19 VACCINE AND 18% HAD A
POSITIVE COVID-19 DIAGNOSIS AND
SIGNIFICANT TO THOSE HAVING
FIBROIDS.
AND THE MEDIAN CYCLE WAS 28.
YOU CAN SEE THE DYSMENORRHEA AND
SEVERITY SCORES ARE IN
COMPARISON TO THE REFERENCE
POPULATIONS IN THOSE VALIDATION
STUDIES.
AND OF NOTE ABOUT 73% HAD
CYCLES.
OVULATE AND THIS WAS EXPECTED
IN PROGESTERONE LEVELS.
ESTRADIOL REMAINED THE SAME.
COMPARED TO ETHNIC REFERENCE
MEANS WERE LOWER BUT THE ETHNIC
REFERENCE STILL DID FALL WITHIN
THE RANGE OF VALUES WE RECORDED.
AND THERE WERE NO SIGNIFICANT
DIFFERENCES RECORDED HEREBY.
-- HERE.
AND HIGHER ESTRADIOL LEVELS WERE
ASSOCIATED WITH LOWER MEAN PAIN
THRESHOLD AND INTERACTION WITH
TIME I'LL EXPLAIN SHORTLY.
IN ADDITION, THE PRESENCE OF OFF
LATER CYCLES AND HYDROXYUREA USE
AND COVID-19 DIAGNOSIS IN THE
LAST SIX MONTHS WERE ASSOCIATED
WITH HEAT PAIN THRESHOLD AS
WELL.
AND THERE'S FIXED AND RANDOM
EFFECTS BY ESTRADIOL LEVELS APPS
AND AS THEY GO UP THE DETECTION
LEVELS GO DOWN BEING NOCICEPTIC
AND LOOKING AT THE PAIN
THRESHOLD BY ESTRADIOL AND THE
DAYS IN THE MENSTRUAL CYCLE THAT
HAVE BEEN STANDARDIZED.
YOU CAN SEE BASICALLY IF THERE
WAS NO INTERACTION THE COLORED
LINE WOULD BE STRAIGHT,
VERTICAL.
FOR EACH VALUE OF ESTRADIOL OR
MARGIN OF ESTRADIOL YOU'D GET
THE SAME PREDICTIVE VALUE.
BECAUSE THERE'S AN INTERACTION
THE LINES BECOME CURVED.
YOU CAN SEE FOR THE SAME VALUE
OF ESTRADIOL THE PREDICTED VALUE
BECOMES HIGHER AT LATER TIMES IN
THE MENSTRUAL CYCLE.
BETWEEN 0 AND 0.1 STANDARDIZED
DAYS IS 36 TO 37 BUT THE SAME
VALUE BETWEEN 0.7 AND 0.8 IS
BETWEEN 43 AND 44.
WE FOUND ESTRADIOL IS
PRO-NOCICEPTIVE AND THE AFFECT
VARIES BY TIME.
THE EFFECT WAS HIGHER EARLIER
TIMES IN THE MENSTRUAL CYCLE AND
WE FOUND IT WITH OUR SENSITIVITY
ANALYSIS AS WELL.
OF COURSE THE TEMPORAL
RELATIONSHIP OF PAIN IS KNOWN.
I MENTIONED THE LANDMARK STUDY
FINDING APPROXIMATELY ONE-THIRD
OF WOMEN WITH SICKLE CELL
DISEASE EXPERIENCED VOC PAIN
AROUND THE TIME OF THEIR MENSES.
WE DID ANTICIPATE FINDINGS WOULD
BE MORE POTENTIATED AT EARLIER
STAGES OF THE MENSTRUAL CYCLE.
I SHOULD MENTION THOUGH THAT
ESTRADIOL LEVELS CERTAINLY DO
NOT PROVIDE AN EXPLANATION FOR
THE TEMPORAL NATURE OF PAIN
BECAUSE ESTRADIOL WAS LOWEST
AROUND THE TIME OF MENSES.
AND WE'D HAVE TO MEASURE THEM AT
DIFFERENT TIME POINTS IN THE
MENSTRUAL CYCLE BUT THE GOOD
POINT IS WE HAVE PRELIMINARY
EVIDENCE TO SUPPORT ESTRADIOL IN
ITS ROLE IN NOCICEPTION IN WOMEN
WITH SICKLE CELL DISEASE.
WE CAN INVESTIGATE THEIR ROLE
IN WOMEN WITH REFRACTORY
NEUROPATHIC PAIN FOR REFRACTORY
CYCLICAL PAIN AND HYDROXYUREA
WAS ASSOCIATED WITH LOWER PAIN
DETECTION LEVELS AND PAIN
SENSITIZATION.
IN JAMAICA WE OFFER HYDROXYUREA
SO WE MAY SEE A RELATIONSHIP
BETWEEN HIGHER PAIN SEVERITY AND
PAIN SENSITIZATION.
AND WE NOTED THERE WAS AN
INCREASE IN IN HYPOTHESIS AND
THERE'S VASO OCCLUSIVE CRISIS AS
THEY AGE AND PERIPHERAL
NEUROPATHY COULD BE RELATED TO
POST INFECTIOUS IMMUNE
DYSREGULATION.
PARADOXICALLY WE FOUND A
PROBABLE DIAGNOSIS OF NEURO
PATHIC PAIN WERE ASSOCIATEDS
WITH HIGHER PAIN THRESHOLDS AND
SHOULD BE NOTES THE ISP DOES
ROYCE NEGATIVE SYMPTOMS AS PART
OF NEUROPATHIC PAIN.
THAT'S ONE POSSIBLE EXPLANATION.
ADDITIONALLY IN A NUMBER OF
STUDIES IT DOESN'T CORRELATE
WELL WITH NEUROPATHIC PAIN AND
MORE A MEASURE OF FIBER
NEUOPATHY AND COULD EXPLAIN
WHERE WE'RE SEEING PATIENTS WITH
HIGHER VOC AND FREQUENCY SCORES
HAVE HIGHER DETECTION AS WELL.
THERE ARE SOME LIMITATIONS.
THE COVID-19 DIAGNOSIS WAS
SELF-REPORTED.
AND THAT'S REALLY REFLECTING
WHEN WAS HAPPENING BECAUSE TAY
WERE DOING TEST KITS AND FELT
THE DATA WAS IMPORTANT TO OMIT.
WE USED THE STEADY STATE BLOOD
VALUES AS LEVEL 2 COVARIATES AND
SOMETHING WE CAN LOOK TO FUTURE
STUDIES AND SHOULD MENTION OF
COURSE INCLUSION CRITERIA
SELECTED WOMEN WITH RELATIVELY
NORMAL MENSTRUAL AND HORMONAL
PHENOTYPES SO IT MAY NOT
ENTIRELY REPRESENT THE WHOLE
POPULATION OF WOMEN WITH SICKLE
CELL DISEASE.
THANK YOU VERY MUCH I WANT TO
ACKNOWLEDGE THE FOUNDATION AND
THESE SUPERVISORS.
AND THERE WERE OTHER
CO-INVESTIGATORS.
THANK YOU.
>> THANK YOU.
THERE'S ONLINE QUESTIONS FOR THE
SAKE OF TIME IF YOU CAN ADDRESS
THEM THAT WOULD BE APPRECIATED.
I THINK WE NEED TO MOVE ON TO
OUR NEXT TALK.
SO THE NEXT TALK IS
IMPLEMENTATION OF INDIVIDUALIZED
PAIN PROTOCOLS THE ALIGN TRIAL
WITH DR. TANABE AND DR. KING.
>> THANK YOU SO MUCH THANK YOU
TO THE NIH AND TO THE PLANNING
COMMITTEE FOR THE OPPORTUNITY TO
PRESENT RESULTS FROM THE ALIGN
TRIAL WHICH IS IMPLEMENTATION OF
INDIVIDUALIZED PAIN PLANS TO
TREAT PAIN IN THE EMERGENCY
DEPARTMENT.
THIS IS ON BEHALF OF MYSELF AND
DR. KING AND SEVERAL
INVESTIGATORS IN THE ROOM.
DR. HSU AND WANG AND OUR DATA
MANAGEMENT ARE HERE AS WELL.
SO THE ALIGN TRIAL WAS ONE OF
THREE IMPLEMENTATION SCIENCE
TRIALS PART OF THE NHLBI FUNDED
SICKLE CELL DISEASE
IMPLEMENTATION CONSORTIUM.
THREE TRIALS WERE IMPLEMENTED
PAIN TRIALS FOR PROVIDER ACCESS
AND FOR THE FIRST TIME EVER FOR
INDIVIDUAL PATIENTS OR WARRIORS
TO HAVE THEIR PAIN TREATED IN
THE EMERGENCY DEPARTMENT.
THERE WERE EIGHT THAT
PARTICIPATED IN THE CONSORTIUM.
ALL EIGHT CENTERS PARTICIPATED
IN THE ALIGN TRIAL.
AND THIS IS FRUSTRATING FOR
INDIVIDUAL WARRIORS AND
EMERGENCY DEPARTMENT PROVIDERS.
TODAY AFTER BEING AT THIS FOR 20
YEARS WE HAVE MADE PROGRESS AND
THERE'S AN OPIOID EPIDEMIC AND
NUMBERS OF OVERCROWDING AND
EMERGENCY ROOM DEPARTMENT.
MY THEME WILL BE PARTNERSHIP AND
THE E.D. PARTNERS ARE IN THE
PLACE OF WANTING TO DO THE RIGHT
THING AND NOW NEED HELP.
THE INDIVIDUALIZED PAIN PLANS AS
RECOMMENDED BY NATIONAL HEART,
LUNG AND BLOOD AND ASH ARE
IMPORTANT.
WE WANTED TO EVALUATE THE
IMPLEMENTATION, CAN WE DO THIS
FOR BOTH PATIENTS AND PROVIDERS.
OUR SECONDARY OUTCOMES WERE E.D.
PROVIDERS OF THEIR CONFIDENCE.
IT'S ONE THING TO HAVE THEM IN
THE CHART OR IN THE PATIENT
PORTAL BUT WILL PATIENTS
ACKNOWLEDGE AND PROVIDERS USE
THEM?
THEY HAD TO HAVE HAD AT LEAST
ONE VISIT TO THE SICKLE CELL
CENTER WITHIN THE LAST YEAR SO
THE SICKLE PROVIDER CAN WRITE AN
INDIVIDUALIZED PAIN PLAN AND
THEY ALSO HAD TO HAVE HAD A
VISIT FOR VOE AT THE E.D. WITHIN
THE LAST 90 DAYS.
SO WE COULD GET A BASELINE
SATISFACTION SCORE FROM THEM OF
THEIR SATISFACTION WITH THAT
VISIT IN THE LAST THREE MONTHS
VERSUS THE VISIT THEY'RE GOING
TO REMEMBER FOREVER IN THE LAST
20 YEARS.
SO ALL THE E.D. PROVIDERS WOULD
BE IN THE SURVEY AND TO BE IN
THE FOLLOW-UP HAD TO BE HAVE A
PATIENT WHO ENROLLED AND
CONCEPTS AND HAD A FOLLOW-UP
VISIT AND SURVEY AS WELL.
EIGHT SITES PARTICIPATED ALL
ACADEMIC CENTERS AND SIX OF THE
EIGHT SITES ALREADY HAD
INDIVIDUALIZED PAIN PLANS
AVAILABLE FOR THE PROVIDER.
AND WE HAD A LITTLE BIT ABOUT
THE DEI AND TRIAL AND HOW TO
TRIAGE PATIENTS AND
INDIVIDUALIZED PAIN PROTOCOLS.
THE SICKLE CELL DISEASE
PROVIDERS WROTE INDIVIDUALIZED
A PLANS FOR FUTURE VISITS IN THE
E.D.
THOSE PLANS WERE THEN MADE
AVAILABLE FOR THE SITES FOR THE
E.D. PROVIDERS AND ALSO MADE
AVAILABLE SO THE PATIENT AND HOW
TO USE PATIENT PORTAL AND
RESEARCH STAFF HELPED THEM TO
MAKE SURE THEY GOT ACCESS TO THE
PORTAL.
A MILLION REASONS WHY THEY NEED
TO HAVE THAT.
THIS WAS A GOOD EXCUSE AND
MOTIVATION FOR INDIVIDUAL
PATIENTS TO ACTUALLY GET ACCESS
AND USE THE PORTAL.
WE ALSO GAVE THE PATIENT A
WALLET CARD.
IT DID NOT HAVE THEIR DOSE ON
IT.
IT GAVE THEM THE INSTRUCTIONS
HOW TO ACCESS THE PLAN FROM THE
E.H.R. FROM THEIR PHONE.
IF ANYBODY WALKS INTO AN E.R.
WITH A LETTER THAT SAYS
DR. SMITH SAYS I GET 2
MILLIGRAMS OF DILATIN IT'D GET
THROWN AWAY AND THE QUESTIONS
WERE TEXTED.
AND IMPORTANTLY THESE WERE SIX
ACADEMIC MEDICAL SITES PRO
SICKLE CELL AND THEY HAD BEEN
WORKING WITH E.D.s AND HAD
INDIVIDUAL PLANS IN THE RECORD
FOR THE EMERGENCY PROVIDER.
SIX OF THE EIGHT.
THE OTHER TWO DID IT FOR THE
TRIAL.
WE HAD 153 PATIENTS WHO
COMPLETED A BASELINE AND
FOLLOW-UP SURVEY ON THE PATIENT
SIDE.
ON THE PROVIDER SIDE MORE
PROVIDERS BUT 135 WHO COMPLETED
A BASELINE AND FOLLOW-UP AND
TREATED A PATIENT WHO HAD AN
INDIVIDUALIZED PAIN PLAN.
THEY COMPLETED THE TEXT SURVEY
AND USING THE SCALE 1-5 WE ASKED
THEM HOW EASY WAS IT FOR YOU TO
FIND IT.
IT'S AN IMPLEMENTATION TRIAL.
WE KNOW HOW WE SHOULD BE
TREATING VASO OCCLUSIVE EPISODES
AND THERE'S EVIDENCE BUT CAN WE
IMPLEMENT THE EVIDENCE.
IT'S VERY MUCH IMPLEMENTATION.
WE WANTED TO KNOW AND E.D.
PROVIDERS DMRECOMPLETED THE SUR
WITH A 1 TO 7 SCORE.
ALL THE PATIENTS WERE PRETTY
SATISFIED AT BASELINE WITH THE
QUALITY OF THEIR CARE.
IF YOU THINK ABOUT IT, SIX OF
THE EIGHT CENTERS ALREADY HAVE
INDIVIDUAL PLANS THE E.D. WAS
USING.
THERE WAS NO IMPROVEMENT IN
SATISFACTION FROM THE BASELINE
BECAUSE WE WERE HIGH TO START
WITH AND NOT SURPRISING E.D.
PROVIDERS WERE CONFIDENT GIVING
THE RIGHT CARE ARE TWO DIFFERENT
THINGS AND NO CHANGE.
60% WERE PRETTY CONFIDENT AND
STAYED THAT WAY.
WE HAD OTHER QUESTIONS WE ASKED
THAT WERE REALLY IMPORTANT.
97.6% OF THE E.D. PROVIDERS
ORDERED WHAT WAS RECOMMENDED.
YOU PUT THE PROTOCOL OUT THERE.
THEY FEEL CONFIDENT AND WILL
ORDER IT.
WHILE WE DIDN'T MEASURE MORPHINE
EQUIVALENTS IN THIS TRIAL AND
THERE'LL BE MORE DATA IN A FEW
MINUTES THEY FOLLOW WITHIN .1
MILLIGRAM.
AND WE'RE WORKING TOGETHER AND
COLLABORATING AND MAKING THEIR
JOB EASIER BECAUSE THEY DO WANT
TO DO THE RIGHT THING IN A VERY
DIFFICULT ENVIRONMENT WITH AN
OPIOID EPIDEMIC AND CRAZY
OVERCROWDING.
WHAT YOU SEE FROM THE FIRST
GRAPHIC ON THE LEFT IS HOW EASY
WAS IT TO FIND IT BECAUSE AGAIN
IMPLEMENTATION CAN THEY FIND IT.
PRETTY EASY IF YOU LOOK AT THE
6s AND 7s IT'S ABOUT 60% OF THE
TIME PEOPLE FOUND IT WAS EASY TO
FIND WE HAD 318 POST SURVEYS WE
SURVEYED THEM MORE THAN ONE
TIME.
THE PRIMARY ANALYSIS WAS JUST UP
WITH VISIT.
WE GOT 318 SURVEYS BACK FROM
PATIENTS.
OVER ALL IT WAS EASY TO FIND.
IMPORTANT TO FIND IT'S NOT EASY
TO FIND FOR EVERYBODY.
EACH INDIVIDUAL WE NEED TO MAKE
SURE THEY CAN FIND IT.
THEN THE SECOND SIDE IS HOW
HELPFUL WAS IT.
HOW HELPFUL WAS THE PLAN IN THE
PAIN TREATMENT YOU NEEDED AND
AGAIN PRETTY HELPFUL.
SIX AND SEVEN OVER 50%.
THE PAIN PLANS WERE HELPFUL.
PATIENTS LIKED IT AND WE HAD AN
ANECDOTE AND I THINK FROM YOUR
SIDE IN CHICAGO WE HEARD ON THE
CALLED ONE PATIENT FROM THE UIC
SITE AND SHOWED IT TO A RANDOM
E.D. DOC IN TEXAS AND THEY
FOLLOWED IT AND WE WERE JUMPING
UP AND DOWN AND THAT'S WHAT WE
WANT.
ONE MORE COMMENT WITH PART OF
THE CDC REGISTRY DOING AN
ANALYSIS OF SUPER UTILIZATION
AND IDENTIFIED PATIENTS IN NORTH
CAROLINA OVER SEVEN YEARS THAT
CAME FROM 25 DIFFERENT STATES IT
SPEAKS TO THE NEED FOR
INDIVIDUALIZED
A PLAN AND 60% SAID THEY HAD A
PLAN.
I THINK THE REASON 30% DIDN'T
WAS THEY KNEW THE E.D. DOC WAS
FOLLOWING THE PLAN IN THE
RECORD.
IN CONCLUSION ALL THE SITES WERE
ABLE TO SUCCESSFULLY IMPLEMENT
THE PLANS AND PUT THEM IN THE
MEDICAL RECORD FOR THE PATIENT
WHICH IS WHERE THEY NEED TO BE.
E.D. PROVIDERS ENDORSE THEM AND
THEY'LL BE FEASIBLE AND FOLLOWED
AND IT REDUCES A LOT OF BARRIERS
TO RECOMMENDED TREATMENT
IMPLEMENTING THE INDIVIDUAL
PLANS.
AS AN ASIDE, WE DID DEVELOP A
FORMAL PROCESS TO HELP THE
SICKLE CELL PROVIDERS WRITE A
PLAN AND THAT IS POSTED.
THE CALCULATOR WHERE WE WORK
WITH DR. STRAUSS TO A FORMAL
PROCESS TO DEVELOP AND HOUSED AT
THE NATIONAL ALLIANCE OF SICKLE
CELL CENTER'S WEBSITE.
WE'RE HAPPY IT'S UP THERE
AVAILABLE FOR FREE AND
QUESTIONS.
>> TERRIFIC WORK.
THIS WARMS MY HEART.
WHAT ARE YOUR RECOMMENDATIONS
FOR SITES NOT PART OF THIS?
I KNOW AT EMORY CHILDREN'S
HEALTH CARE OF ATLANTA THEY HAVE
INDIVIDUAL PAIN PLANS.
AS A DOC I CAN'T FIND THEM.
I LOOK AND THEN GIVE UP AND TRY
TO DO THE RIGHT THING FOR THE
PATIENT.
>> WHERE DO YOU FIND THE PLAN IS
THE QUESTION.
I RECOMMEND THE
MULTIDISCIPLINARY TEAM WHERE YOU
HAVE AN E.R. DOC AND SICKLE CELL
DOC AND SOMEONE TO WORK WITH THE
ELECTRONIC HEALTH RECORD AND
TRYING TO FIND A PLACE TO FIND
IT AND TALKING ABOUT THE LAST
OUT PATIENT VISIT BECAUSE MANY
TIMES THAT RECORD IS SO MANY
VISITS YOU CAN'T FIND IT.
WE HAVE A SNAPSHOT VIEW AND THE
PLAN IS THERE.
IF IT CHANGES THEY NEED TO
CHANGE IT THERE.
IT'S ONE PLACE.
OTHER PLACES DO IT AS AN FYI TAB
IN THE E.H.R.
I THINK YOUR PARTICULAR CENTER
YOU HAVE TO GET TOGETHER AND
TELL THEM WE CAN'T FIND IT.
IT'S GREAT YOU'RE WRITING THIS
BUT WE CAN'T FIND IT SO PUT IT
SOMEWHERE WHERE YOU CAN FIND IT
AND WORK TOGETHER TO GET IT
THERE.
THEN THERE'S THE KEEPING IT UP
TO DATE.
OFTEN THAT IS ALSO UP TO THEM AS
WELL.
HAVING A BPA AND GO TO ORDER THE
MEDS AND THE BPA POPS UP AND
SAYS GIVES THE PERSON THIS.
A LOT OF PEOPLE DON'T GET A LOT
OF OPIOIDS AND THOSE PEOPLE CAN
BENEFIT FROM WEIGHT BASED.
THAT WOULD BE MY RECOMMENDATION
THE PARTNERSHIP.
>> IF YOU USE EPIC THERE'S A
PLACE OF EMERGENCY CARE PLANS
BUILT INTO THE GENERIC VERSION.
I KNOW YOU MAY NOT HAVE IT BUT
THEY USE THIS FOR PEOPLE THAT
FREQUENTLY USE THE EMERGENCY
ROOM DEPARTMENT.
WE ORIGINALLY PUT OUR IPPs IN
CARE COORDINATION UNDER SNAPSHOT
AND THE EMERGENCY ROOM PEOPLE
SAID NO WE WANT THEM IN THIS
PLACE AND GOES IN THEIR GENERAL
WORK FLOW BUT IT DEPENDS ON THE
E.R.
I ASSUME THE OTHER VENDORS HAVE
A SPECIFIC PLACE FOR THINGS LIKE
THAT AS WELL.
>> THANK YOU, DR. WANG.
AND GET IT FOR THE PATIENT FOR
THE PATIENT PORTAL.
>> DANIEL IVY.
I WANTED TO ASK ABOUT YOUR NEXT
STEPS.
IT'S WONDERFUL THE WORK AT THE
SICKLE CELL CENTERS BUT HAVE YOU
THOUGHT ABOUT WHAT YOU'LL DO
NEXT AND USING THE NORTH
CAROLINA APEX OR OTHER EXISTING
PROGRAMS WITH THE STATE
GOVERNMENT TO PUSH THIS OUT TO
OTHER E.D.s IN RURAL AREAS.
>> THANK YOU FOR THE QUESTION.
IT'S FUNNY YOU MENTION NORTH
CAROLINA.
WE'VE BEEN WORKING FOR FOUR
YEARS NOW TO DEVELOP THE TOOLBOX
AND DISSEMINATE.
WITH PARTNERS ACROSS THE STATE
FROM EMERGENCY MEDICINE AND FROM
SICKLE CELL ACROSS THE STATE TO
DISSEMINATE THE TOOLBOX THROUGH
THE CEOs OF THE TOP 20 HOSPITALS
THAT HAVE THE HIGHEST NUMBER OF
E.D. VISITS TO CEO AND NURSING
AND MEDICAL DIRECTORS AND
WORKING WITH THOSE ASSOCIATIONS.
YOU'RE RIGHT, IT'S TIME FOR A
BIGGER DISSEMINATION AND I THINK
THERE'S A PENDING MEASURE ABOUT
TIME TO FIRST DRUG.
SO BETWEEN ASH AND CMS AND
LARGER ORGANIZATIONS IT'S TIME.
WE'VE SHOWN WE CAN DO IT SO WE
DO HAVE TO DISSEMINATE IT NOW.
THERE'S A CHAIR AND I THINK I'LL
BE THE CHAIR ELECT AFTER THAT.
THERE'S A GREAT TOOL ON THE ASAP
WEBSITE AND THE TOOL IS THE
NUMBER DECISION SUPPORT TOOL
THAT HAS EVER BEEN OUT FROM ASEP
WHICH IS A HUGE THING TO BE ABLE
TO SAY.
THE FACT ASAP AND MY ENA
ORGANIZATION I THINK WE'VE MADE
A WHOLE LOT OF PROGRESS DESPITE
THE BARRIERS WE STILL HAVE AND
HAVE PROFESSIONAL ASSOCIATIONS
BEHIND THEM AND CAN NO LONGER
SAY E.D.s DON'T WANT TO DO IT
BUT SAY HOW DO WE HELP THEM DO
IT.
>> WHAT IS THE PLATFORM?
>> EPIC AND SERNER.
EPIC IS EPIC FOR YOU AND ME AND
EACH IS A LITTLE DIFFERENT AND
ALISON KING HAS MORE DETAILED
GOOD EXAMPLES OF HOW YOU CAN DO
IT IF YOU'RE ON EPIC TO MAKE IT
SUPER, SUPER EASY.
>> HOW CAN WE GET ACCESS TO THE
PORTAL AND START TO ADDRESS THE
IMPROVEMENT
>> I'M HAPPY TO CONNECT WITH
ANYONE OR CONNECT IN THE
HOSPITAL FROM MARLIN IMABAGO.
>> YOU CAN GET THE CALCULATOR.
THE TOOLBOX IN NORTH CAROLINA
WE'RE GETTING A LOT OF REQUESTS
FOR THAT ALREADY AND START THE
DISSEMINATION ON SEPTEMBER 1.
I DON'T HAVE PERMISSION TO SHARE
THAT YET BUT IF YOU E-MAIL ME I
CAN SHARE ALL KINDS OF STUFF.
>> ONE MORE.
GREAT PRESENTATION.
WHAT ARE YOUR THOUGHTS ON HOW WE
CAN MAKE IPPs STANDARD OF CARE
AND THERE BE REDUCING THE BIASES
AND ACCESS ISSUES PATIENTS OF AN
EXPERIENCE.
WE HAVE TO GET PATIENTS MORE
ENGAGED TO REQUEST THE PLANS
BECAUSE THE SICKLE CELL PROVIDER
HAS TO WRITE THE PLAN.
AND THEN THEY HAVE TO ENGAGE
THEIR E.D.
I THINK THAT WOULD BE
PROFESSIONAL ASSOCIATIONS,
PATIENTS DRIVING IT.
I THINK ALL OF US DRIVING IT
TOGETHER AND MAYBE THE CMS
MEASURE WILL HELP WITH
MOTIVATION.
>> ONE MORE.
>> A COMMENT FROM JULIE KANTER.
THERE'S A QR CODE TO LINK TO THE
PATIENT'S PLAN IN THE SICKLE
CELL DISEASE REGISTRY.
>> THANK YOU FOR THE UPDATE.
LET'S GO TO THE NEXT TALK
METABOLIC REPROGRAMMING OF
MACROPHAGES BY SICKLE CELL
HEMOGLOBIN BY MARINA JEREBTSOVA.
FROM HOWARD UNIVERSITY COLLEGE
OF MEDICINE.
>> GOOD MORNING.
THANK YOU FOR GIVING ME THE
OPPORTUNITY TO PRESENT OUR DATA
AT THIS MEETING.
AND THE LOW OXYGEN PRESENTS
HEMOLYSIS AND FREE PLASMA
HEMOGLOBIN AND THERE'S
APPROXIMATEL
APPROXIMATELY HEMOGLOBIN IN
CIRCULATION AND THE MACROPHAGE
HAPPEN IN THE SPLEEN.
IF INDUCED ANTIINFLAMMATORY
PHENOTYPE OF PLAQUE ROW FAITH.
-- MACROPHAGE AND THERE'S
LYSOSOMES AND AUTOPHAGOSOMES
WITH PRO-INFLAMMATORY PHENOTYPE
AND THAN POLYMERIZE AT LOW PH
AND THIS ANY DELAY ITS
DEGRADATION IN LIYSOSOMES AND G
TO THE PROINFLAMMATORY
PHENOTYPE.
DIFFERENTIATION OF MACROPHAGE TO
THE SPECIFIC PHENOTYPE IS
USUALLY ASSOCIATED WITH THE
METABOLIC PROGRAMMING.
AND THIS REPRESENTS THE
POLYMERIZATION OF HEMOGLOBIN IN
THE RED BLOOD CELLS AND
CAPILLARY SICKLE CELL DISEASE
MOUSE.
AND WE LOOK AT THE THP-1 CELL
LINE DIFFERENTIATED INTO THE
MACROPHAGE AND WE USE NORMAL
HEMOGLOBIN A AS A CONTROL FOR
THE MODIFICATION OF THE
MACROPHAGE PHENOTYPE.
WE ALSO USE SICKLE CELL DISEASE
MOUSE MODEL.
THREES TWO APPROACHES.
AND WE LOOK AT THE MIGHT CON --
MITOCHONDRIAL PROBE AND IT
REPRESENTS THE PROBE.
THE BLUE COLOR REPRESENTS THE
STAINING OF NUCLEUS.
AND HERE IS A WHITE OUTLINE OF
THE STAINING QUANTIFICATION OF
THE PAIR CELLS.
AND BOTH DEMONSTRATE SIGNIFICANT
INCREASE OF THEIR MITOCHONDRIA
IN MACROPHAGE HEMOGLOBIN
COMPARED TO THE MACROPHAGE
TREATED WITH HEMOGLOBIN.
AND THREES AN INCREASE IN THE
NUMBER OF MITOCHONDRIA IN THE
MACROPHAGE IN SICKLE CELL
HEMOGLOBIN NOT ONLY THE NUMBER
QUANTIFIED IN THE MICROSCOPE BUT
THE SIZE OF MITOCHONDRIA AND
INCREASE IN THE MACROPHAGE STAGE
OF SICKLE CELL HEMOGLOBIN.
AND YOU CAN ANALYZE THE RNA SEQ
DATA AND THERE WAS A PATHWAY IN
THE ENRICHMENT ANALYSIS.
AND WE CAN COMPARE SAMPLES.
WE COMPARE MACROPHAGE FOR SICKLE
CELLS AND TREATED WITH NORMAL
HEMOGLOBIN.
AND THE NUMBER OF EXPRESSION IN
THE MACROPHAGE TREATED WITH
SICKLE CELL HEMOGLOBIN.
THERE'S GENERIC CUSTOM CELLS
ANALYSIS FOR 242 GENES.
WE ALSO PERFORMED ANALYSIS OF
THE GENES FOR GLYCOLYSIS AND
MITOCHONDRIAL INFUSION.
THE INCREASED NUMBER WITH IN
CONTRAST INCREASE THE SIZE OF
MITOCHONDRIA CAN BE ASSOCIATED
WITH THE MITOCHONDRIAL FUSION
BUT WE DID NOT FIND SIGNIFICANT
DIFFERENCE IN THE THOSE TREATED
WITH THE SICKLE CELL HEMOGLOBIN.
SO THE INCREASE OF MITOCHONDRIAL
MAY AFFECT THE FUNCTION OF
MITOCHONDRIA.
WE FIRST TESTED THE PRODUCTION
OF MITOCHONDRIA.
WE DID NOT FIND A DIFFERENCE
BETWEEN THE PRODUCTION OF
MITOCHONDRIAL BETWEEN THE
CONTROL MACROPHAGE TREATED WITH
HEMOGLOBIN S AND IT SLIGHTLY
DECREASED PRODUCTION OF
MITOCHONDRIAL ROS AND WE
DEMONSTRATED THE PRODUCTION OF
MITOCHONDRIAL ROS IN OUR SYSTEM.
THERE'S ALSO THE PRODUCTION OF
THP AND HEMOGLOBIN S REDUCED
SIGNIFICANTLY MORE ATP AND THE
AMOUNT OF HTP1 DERIVED
MACROPHAGE AND THERE'S NO
LIMITATION FOR THE OXYGEN IN
THIS PROCESS IN THE CELLS.
AND THERE'S MOSTLY MACROPHAGES
IN THE DIGESTION OF THE RED
BLOOD CELLS MICE AND ATP
PRODUCTION AND SICKLE CELL
DISEASE MICE SIGNIFICANTLY
INCREASED.
WHAT WAS INTERESTING IS WE FOUND
SIGNIFICANT INCREASE IN THE
SPLENNOCYTES.
IN CONCLUSION, TREATMENT OF
HUMAN MACROPHAGE INCREASED THE
NUMBER AND VOLUME OF
MITOCHONDRIA AND THE SIZE OF
PHOSPHORYLATION AND ATP
PRODUCTION AND UP REGULATION OF
M ROS PRODUCTION AND INCREASED
MITOCHONDRIAL SIZE AND ATP
PRODUCTION AND MACROPHAGE
TREATED WITH HEMOGLOBIN MAY
REFLECT DIFFERENTIATION INTO THE
LONG-TERM PRO INFLAMMATORY
PHENOTYPE CALLED TRAINED
IMMUNITY OR INMATE IMMUNE SYSTEM
MEMORY.
THIS CAN EXIST IN THE MACROPHAGE
TWO TO SIX MONTHS AND BECAUSE
IT'S ASSOCIATED WITH THE E
EPIGENETIC CHANGE IN MACROPHAGE
TREATED WITH SICKLE CELL
HEMOGLOBIN.
THANK YOU.
>> QUESTIONS?
NO IN PERSON OR ONLINE
QUESTIONS?
THANK YOU VERY MUCH FOR YOUR
TALK.
SO LET'S MOVE ON TO THE NEXT
TALK FROM DR. STEPHANIE IBEMERE
AND PAIN PROTOCOL FOR EMERGENCY
ROOM DEVELOPMENT OF VASO
OCCLUSIVE EPISODES.
>> I'M AN ASSIST THE DUKE
UNIVERSITY SCHOOL OF NURSING AND
WITH GREAT POWER COMES GREAT
RESPONSIBILITY AND I'M STANDING
BETWEEN YOU AND YOUR LUNCH SO I
PROMISE NOT TO GO OVER TIME AND
APPRECIATE BEING HERE.
TODAY I'LL BE PRESENTING SOME
DATA FROM A MANUSCRIPT CURRENTLY
UNDER REVIEW ENTITLED IMPACT OF
INDIVIDUALIZED VERSUS
WEIGHT-BASED PAIN PROTOCOL ON
PATIENT SATISFACTION FOR
PATIENTS WITH SICKLE CELL
DISEASE EXPERIENCING VASO
OCCLUSIVE EPISODES.
AS YOU SAW A COUPLE SECONDS AGO
I DO NOT HAVE DISCLOSURES
PERTINENT TO THIS PRESENTATION.
I'LL BE PRESENTING SECONDARY
ANALYSIS THAT COMES FROM THE
COMPARE VOE TRIAL FUNDED WE THE
NATIONAL HEART, LUNG AND BLOOD
INSTITUTE.
I WANT TO THANK THEM FOR
SUPPORTING OUR RESEARCH.
INDIVIDUALS WHO LIVE WITH SICKLE
CELL DISEASE OFTEN EXPERIENCE
UNPREDICTABLE AND FREQUENT VASO
OCCLUSIVE EPISODES.
THEY CARRY WITH THEM WHAT CAN BE
AN EXTREME AND SOMETIMES
INDESCRIBABLE PAIN THAT OFTEN
NECESSITATES EMERGENCY ROOM
DEPARTMENT CARE AND INTRAVENOUS
OPIOID ADMINISTRATION.
UNFORTUNATELY THE WORK OF
DR. HAYWOOD AND DR. BALLGIN AND
OTHERS HIGHLIGHTED THAT DESPITE
THE REALITY, THE REALNESS, THE
RAWNESS OF THE PAIN INDIVIDUALS
FEEL DURING THESE VASO OCCLUSIVE
EPISODES, THEY OFTEN ENCOUNTER
STIGMA AND ARACIAL BIAS IN THE
EMERGENCY ROOM DEPARTMENT WHEN
SEEKING CARE.
AFTER YEARS AND YEARS OF THOSE
EXPERIENCES AND COLLECTING
ANYTHING TICH S IN EMERGENCY
ROOM DEPARTMENT MANY SICKLE CELL
WARRIORS DECIDE TO DELAY THEIR
CARE AND THESE DELAYS ARE WHAT
WITH CONSIDER CONTRIBUTION TO
THE INCREASED MORBIDITY AND
MORTALITY RELATED TO SICKLE CELL
DISEASE.
SO, IN THE CONTEXT OF THIS
MILIEU THE NATIONAL HEART, LUNG
AND BLOOD INSTITUTE IN 2014 AND
THE AMERICAN SOCIETY FOR
HEMATOLOGY IN 2020 DEVELOPED
GUIDELINES OR RECOMMENDATIONS
FOR HOW WE COULD TREAT VASO
OCCLUSIVE EPISODES AND MADE THE
RECOMMENDATION WE SHOULD BE
TREATING THESE ACUTE EPISODES
USING A PATIENT SPECIFIC
PROTOCOL OR WHAT THEY LABELLED A
STANDARD PAIN PROTOCOL.
IN THIS PARTICULAR PARENT STUDY
WE WERE TALKING ABOUT THE
COMPARISON OF A PATIENT-SPECIFIC
PAIN PROTOCOL AND THE
WEIGHT-BASED PAIN PROTOCOL IN
THE REDUCTION OF A PAIN SCORE
MEASURED BY A 0 TO 100 VISUAL
SCALE ANALOG SCALE DEVICE.
IN THIS STUDY WE OPERATIONALIZED
THE STANDARD OPIOID PROTOCOL AS
A WEIGHT-BASED PAIN PROTOCOL.
IN MY STUDY I'M TALKING ABOUT
THE COMPARISON OF THE PATIENT
SATISFACTION PROTOCOL TO THE
WEIGHT-BASED PAIN PROTOCOL IN
THE MEASUREMENT OF PATIENT
SATISFACTION IN THE STUDY.
SO, TO BE INCLUDED THERE WERE
SIX SITES.
THE STUDY SITES HAD TO MEDE
CERTAIN CRITERIA.
THERE HAD TO BE A HEMATOLOGIST,
READY, WILLING AND ABLE TO
DEVELOP THE PAIN PROTOCOLS FOR
EACH PATIENT RANDOMIZED.
YOU CAN'T DO MUCH WITH A
DOCUMENT THAT CAN'T GET
INTEGRATED IN THE ELECTRONIC
HEALTH RECORD.
SO YOU HAVE I.T. SPECIALISTS
READY, WILLING AND WAITING TO
SUPPORT THE PROTOCOLS IN THE
ELECTRONIC HEALTH RECORD.
CAPACITY TO HANDLE A RESEARCH
STUDY OF THIS SIZE WAS
IMPERATIVE FOR US AND WANTED TO
KNOW THE SITES HAD AT LEAST TWO
SICKLE CELL DISEASE RELATED
EVENTS AT THEIR SITES.
IT'S IMPORTANT TO NOTE IN THE
SITES THERE WERE NO PREVIOUS
USES OF A PAIN PROTOCOL SPECIFIC
FOR VASO OCCLUSIVE EPISODES IN
THE EMERGENCY ROOM DEPARTMENT.
ALL STUDY PARTICIPANTS WHO
PARTICIPATED OVER 18 HAVE ONE OF
THESE FOUR GENOTYPES AND HAD AN
EMERGENCY ROOM DEPARTMENT VISIT
AFTER BEING RANDOMIZED AND
COMPLETED THEIR EMERGENCY ROOM
DEPARTMENT AFTER THEIR E.D.
VISIT.
ALL THE PARTICIPANTS RECRUIT AND
ENROLLED WERE BLIND TO THEIR
STUDY ARM IN THE STUDY.
IN TERMS OF THE METHODS THAT
WERE USED FOR COMPARE OF THE
STUDY PRIOR TO BEING RANDOMIZED
WE CONDUCTED PRE-ENROLLMENT.
YOU MAY SCRATCH YOUR HEAD AS TO
WHAT THAT MEANS.
PRE-ENROLLMENT IS RELATED TO US
CONSENTING TO PARTICIPANTS
BEFORE THEY HAD THEIR E.D. VISIT
BECAUSE WE DIDN'T FEEL IT WAS
WISE TO HAVE THEM IN THE VASO
OCCLUSIVE EPISODES IN THE
EMERGENCY ROOM DEPARTMENT.
ONCE PRE-ENROLLED A PARTICIPANT
WOULD BE RANDOMIZED AND THERE
WAS AN OPIOID CALCULATOR TO
DEVELOP THE PAIN PROTOCOLS.
THAT WAS USED IN CONJUNCTION
WITH MEDICAL HISTORY INFORMATION
WHICH INCLUDED THE TYPES AND
DOSES OF OPIOID THAT WERE USED
ON THAT PARTICIPANT'S MOST
SEVERE PAIN DAY AND PREVIOUS USE
OF OPIOIDS THAT COULD BE
COLLECTED FROM CHART REVIEW.
SHOULD THE HEMATOLOGIST HAD HAD
ANY ISSUE IN DEVELOPING THE PAIN
PLANS THEY HAD ACCESS TO THREE
HEMATOLOGY EXPERTS TO SUPPORT
THEM IN THE DEVELOPMENT OF THE
PAIN PROTOCOLS.
ALL YOU NEED TO GO IS TO THE
NATIONAL ALLIANCE OF THE OPIOID
WEBSITE TO GET THE CALCULATOR.
AND A LOT OF HARD WORK WENT INTO
BUILDING THAT CALCULATOR.
AS PART OF THE STUDY I AM
PRESENTING TODAY PARTICIPANT
SATISFACTION WITH PAIN
MANAGEMENT WAS COLLECTED AS PART
OF THE LAST DATA COLLECTION
POINT IN THE SIX HOUR STUDY
VISIT OR HOSPITAL DISPOSITION.
WHATEVER THE FINAL DATA POINT
WAS AND ANALYSIS OF SATISFACTION
BETWEEN THE PROTOCOLS WAS
CONDUCTED USING A TWO-SAMPLE T
TEST AND HEISBERG TEST.
THE MEAN AGE OF OUR PARTICIPANTS
WAS 30 YEARS.
THE MOST HIGHLY REPRESENTED
GENOTYPES WERE SS AND SICKLE
BETA THALASSEMIA.
MOST WERE FEMALE AND AFRICAN
AMERICAN AND THE BASELINE PAIN
SCORE WAS APPROXIMATELY 80.
I WANT TO HIGHLIGHT IN THE TRIAL
THE PRIMARY OUTCOME SHOWED A 34%
REDUCTION IN PAIN.
THOUGH THE DIFFERENCE BETWEEN
THE TWO PROTOCOLS WAS NOT
SIGNIFICANT.
THERE WAS A 26.5 POINT REDUCTION
IN PAIN SCORE IN THE COMPARABLE
VOE TRIAL WHICH WAS CLINICALLY
SIGNIFICANT.
SO IS PATIENT SATISFACTION.
SO FOR OVER ALL THE 40% OF THE
PARTICIPANTS FELT THEIR PAIN WAS
RELIEVED ENOUGH TO BE DISCHARGED
HOME AT THE END OF THE STUDY.
YOU CAN ALSO SEE THOUGH IT
WASN'T STATISTICALLY SIGNIFICANT
A LARGE PORTION OF INDIVIDUALS
RANDOMIZED TO THE SPECIFIC
PROTOCOL BELIEVED THE E.D. STAFF
HAD DONE EVERYTHING TO CONTROL
THEIR PAIN AND THE WEIGHT-BASED
PROTOCOL SHOWED THE SAME NUMBER
OF PARTICIPANTS SUGGESTING THEIR
PAIN WAS WELL CONTROLLED BY THE
E.D. STAFF AND THE PROTOCOL WHO
STATED THEY WERE SATISFIED WITH
THE PAIN MANAGEMENT COMPARED TO
THE PAST IN THIS PARTICULAR
STUDY.
SO IF YOU LOOK AT THE VERY LAST
PART OF THE BOX IN THE RED
YOU'LL SEE THE PATIENT SPECIFIC
GROUP WAS AT 57% OF THE GROUP
SAYING THEY WERE VERY SATISFIED
COMPARED TO THE WEIGHT-BASED
GROUP ONLY 31%.
INTERESTINGLY NEARLY 80% OF THE
OVER ALL SAMPLE STATED THEY WERE
SOMEWHAT OR VERY SATISFIED WITH
THE PAIN MEDICINE THEY RECEIVED
DURING THE TRIAL AS WELL.
THERE WAS ALSO NO DIFFERENCE
BETWEEN THE GROUPS IN TERMS OF
REACHING THEIR ORIGINAL PAIN
GOAL THIS SHOWS THE DECISION.
34 PARTICIPANTS DISCHARGED HOME,
91% FELT THEY WERE READY TO BE
DISCHARGED AND THEIR PAIN HAD
BEEN RELEASED SUFFICIENTLY TO BE
RELEASED HOME AND 90% WHO DID
NOT HAVE THEIR PAIN RELEASED
WERE ADMITTED TO THE HOSPITAL.
OF THE FIVE UP TREATMENT OR IN
THE STUDY VISIT FOR SIX HOURS
BUT NOT RECEIVED A DISPOSITION
DECISION 80% DID NOT BELIEVE
THEIR PAIN WAS SUFFICIENTLY
RELIEVED TO BE DISCHARGED HOME.
YOU MAY ASK YOURSELF THE STORY
AND THE MORAL OF THE STORY, WHY
ARE YOU TELLING ME ALL THIS?
THE MORAL IS WHETHER YOU USE THE
PATIENT SPECIFIC PAIN PROTOCOL
OR WEIGHT-BASED PAIN PROTOCOL,
YOUR PATIENTS ARE GOING TO BE
SATISFIED.
THAT'S SOMETHING WE'VE BEEN
CHASING AFTER A LONG TIME.
THE DATA WE COLLECTED IN THE
COMPARED VOE TRIAL GIVES THE
INFORMATION TO GIVE THE PAIN
PROTOCOLS TO MAKE PATIENTS
SATISFIED WITH THEIR CARE IN THE
EMERGENCY ROOM DEPARTMENT.
A GREATER PROPORTION OF THEIR
PAIN MANAGED WITH A PLAN
COMPARED TO A WEIGHT-BASED
PROTOCOL WERE SATISFIED WITH
THEIR CARE AND I THINK THE PAIN
PROTOCOLS OFFERS AN OPPORTUNITY
TO IMPROVE CARE AND EXPERIENCES
OF OUR SICKLE CELL WARRIORS IN
THE EMERGENCY ROOM DEPARTMENT
AND AS DR. TANABE SAID A WAY TO
SUPPORT CLINICAL TEAMS IN MAKING
GOOD EVIDENCE-BASED DECISIONS
HOW TO MANAGER VOE IN THE
EMERGENCY ROOM DEPARTMENT.
I CANNOT DO THIS PRESENTATION
WITHOUT TAKING A MINUTE TO SAY A
MASSIVE THANK YOU TO THE SICKLE
CELL WARRIORS AND THEIR FAMILIES
WHO OPTED TO PARTICIPATE IN THE
STUDY.
WE AS SCIENTISTS IN THE ROOM
CANNOT DO OUR WORK WITHOUT THEM
AND OWE THEM A GREAT DEBT OF
GRATITUDE AND I LISTED THE
AUTHORS FOR THE MANUSCRIPT ON
THE SLIDE AND WANT TO THANK THEM
EACH FOR THEIR SUPPORT AND
GUIDANCE AS WE DID THE
MANUSCRIPT AND ANALYSIS AND TAKE
A MOMENT TO SAY A BIG THANK YOU
TO DR. PAULA TANABE FOR BEING A
GREAT MENTOR TO ME.
I STARTED AS A POSTDOC AND WAS
ABLE TO TRANSITION TO BEING A
CO-INVESTIGATOR SO IT'S BEEN A
GREAT LEARNING OPPORTUNITY FOR
ME AS I GROW MY OWN PERSONAL
RESEARCH PROGRAM.
THANK YOU ALL SO MUCH FOR
LISTENING.
I PROMISED NOT TO GO OVER TIME.
>> ON WEIGHT BASED VERSUS
PERSONAL -- THE SECRET IS OUT OF
THE BAG AND THERE'S A PAIN SCORE
THAT WAS CLINICALLY RELEVANT.
THERE'S A PAIN PLAN THEY WERE
TREATED ON DID THEY KNOW WHICH
PAIN PLAN THEY HAD BEEN
RANDOMIZED TO?
>> THEY DID NOT KNOW.
THEY WERE BLINDED IN THE STUDY
AND DIDN'T KNOW IF THEY WERE
PATIENT SPECIFIC OR WEIGHT
BASED.
>> THANK YOU.
>> YOU'RE WELCOME.
>> FANTASTIC JOB, DR. IBEMERE.
IN THE DOSING, IN THE WORK WE
DID PRIOR TO THE COMPARE STUDY,
WE HAD TWO SITES AND DID NOT
GIVE A CALCULATOR.
WE DID NOT TELL HEMATOLOGISTS
HOW TO WRITE THE PLAN.
IN THAT STUDY, WHICH WAS NOT
TOTALLY POWERED FOR THE OUTCOME
THE PATIENTS GOT A SIGNIFICANTLY
HIGHER DOSE THAN THE WEIGHT BASE
AND HAD AN IMPROVEMENT UP THEIR
PAIN SCORE AND WE DID NOT REACH
OUR FINAL SAMPLE SIZE BECAUSE OF
COVID BUT THE DOSES WERE THE
SAME AND WERE LOWER THAN THE
PILOT WORK HOWEVER, WE DESIGN
THE CALCULATOR TO BE VERY
USER -- TO BE DISSEMINATED FOR
WIDESPREAD USE WITH THE GOAL OF
SAFETY IN MIND.
IT'S A VERY SAFE CALCULATOR.
IF YOU LOOK AT THE PAPER
PUBLISHED I THINK IN ACADEMIC
EMERGENCY MEDICINE ON THIS
YOU'LL SEE LOTS OF GREAT SIDE
EFFECT DATA IT WAS ALL TOTALLY
SAFE, NO NARCAN, NO PROBLEM.
IT SHOWED CONFIDENCE IN PEOPLE
IN USING THE CALCULATOR.
BUT WITH EVERYTHING CLINICAL AS
YOU WRITE THE PROTOCOLS IF THE
DOSE LOOKS TOO LOW THEN IT
SHOULD BE TOO HIGH.
SOME PATIENTS HAD
EXTRAORDINARILY HIGH DOSES FROM
THE CALCULATOR AND TWO OR THREE
THE TEAMS DECIDED NOT TO ENROLL
BECAUSE THE DOSE WOULD NEVER BE
GIVEN NO MATTER WHAT.
THANK YOU.
>> THANK YOU.
>> SO, QUESTION HERE AND HAVE
YOU LOOKED AT IF USING A
PROTOCOL CAN HELP PROVIDERS EASE
THEIR ANXIETY ABOUT PRESCRIBING
OPIOIDS.
>> I THINK FROM THE ALIGN STUDY
THEY FELT COMFORTABLE USING THE
DEVELOPEDIZED -- INDIVIDUALIZED
OR PATIENT SPECIFIC PROTOCOLS
BUT THERE'S ROOM TO DO IN THAT
AREA IN ADVOCACY AND WE HAVE
SOME OF THAT DATA FROM THE ALIGN
TRIAL.
>> THAT'S GREAT.
THE THOUGHT BEHIND THE QUESTION
IS PROTOCOLS CAN HELP MITIGATE
BIASES.
IT DOESN'T MATTER WHAT YOU THINK
ABOUT THE PERSON SO THAT'S
GREAT.
THANKS.
>> I'M WITH YOU 100%.
I HAD WANTED TO MENTION IN THE
PRESENTATION TOO THIS DEPICTION
OF THE STIGMA AND RACIAL BIAS
PEOPLE EXPERIENCE IS COMING
THROUGH ON TV SHOWS.
IF YOU HAVEN'T SEEN IT YET,
THERE'S LOTS OF NETFLIX SERIES.
ONE CALLED LENNOX HILL THAT
DEPICTS WHAT I WAS DESCRIBING IN
THE INTRODUCTION OF MY
PRESENTATION.
THANK YOU, EVERYBODY.
>> THANK YOU.
OKAY, SO WE'RE GOING TO BREAK
FOR LUNCH AND COME BACK PROMPTLY
AT 1:30.
SO WE HAVE STILL VERY
INTERESTING TALKS LEFT FOR THE
REST OF THE DAY.
SEE YOU AT 1:30.
>> OKAY.
GOOD AFTERNOON, EVERYBODY.
WE ARE BACK WE'RE GOING TO GET
STARTED WITH OUR LAST SYMPOSIUM
FOR THE MEETING AND FOR TODAY.
THIS IS OUR THIRD ON UPDATES ON
CIRCLE RBC NEUTROPHIL
INTERACTIONS.
DR. GRACE LEE.
>> OKAY AS EVERYONE IN THE
AUDIENCE KNOWS, NEUTROPHILS ARE
INCREASINGLY RECOGNIZED AS
CONTRIBUTORS TO SICKLE CELL
DISEASE.
IT'S BEEN NOBODY LEUKOCYTOSIS IS
RELATED TO COMPLICATIONS AND
EARLY DEATH AND NEUTROPHILS ARE
ACTIVATED AND FUNCTIONALLY
ABNORMAL AND FOUND TO HAVE
ADHESIVENESS TO THE ENDOTHELIAL
CELLS AND RELATED TO
COMPLICATIONS.
NEUTROPHILS FROM SICKLE CELL
DISEASE PATIENTS ARE ALSO MORE
PRONE TO EXTRA CELLULAR TRAP OR
NET RELEASE AND PATIENTS WITH
VASO OCCLUSIVE CRISIS AND ACUTE
CHEST SYNDROME HAVE INCREASED
AMOUNTS IN THEIR PLASMA.
IN PRIOR WORK IN SOME CONDITIONS
THEY ARE PREINCUBATED BEFORE
EXPOSING THEM TO NEUTROPHILS.
THEY'RE QUANTIFIED.
IN THE UPPER LEFT HAND GRAPH SS
RED BLOOD CELLS HAVE MORE
ADHESION AND EXPOSURE TO
EPINEPHRINE CAUSES FURTHER
ADHESION.
WE CHOSE TO FOCUS ON THE A
TERTIARY GRANULE FOR NEUTROPHILS
AND THEY WERE OFFERED FOR SS RED
CELLS AND THEY CAUSED THEM TO
DEGRANULATE AND NEUTROPHILS WERE
INCUBATED AND AFTER THREE HOURS
THE RELEASE OF THE NET COMPONENT
WAS MEASURED.
YOU CAN SEE SS RED CELLS CAUSED
MORE NET RELEASE.
TOGETHER THE PREVIOUSLY
PUBLISHED STUDIES SHOWED SS RED
CELLS DIRECTLY ACTIVATE
NEUTROPHILS AND CONTRIBUTE TO
THE ACTIVATION.
THE GOAL IS TO DETERMINE IF THE
RED CELL EXCHANGE CAN DECREASE
ACTIVATION.
SO WITH IRB APPROVAL AND
INFORMED CONSENT WE ENROLLED
FROM THE DUKE OUT PATIENT
APHERESIS CLINIC AND THE ASSAY
FOCUSES ON TERTIARY GRANULAR
RELEASE AND NEUTROPHILS HAVE AN
AGONIST AND WE ALSO QUANTIFIED
RED CELL EXPOSURE USING FLOW
CYTOMETRY.
WE ENROLLED 22 PATIENTS FROM OUR
CLINIC.
EXACTLY HALF WERE MALE AND 11
MALES AND THE AVERAGE AVERAGE IS
20 TO 60.
PATIENTS WERE UNDERGOING ROUTINE
RED CHEL EXCHANGE AND THE COMMON
HISTORY WAS FOR STROKE THE
INDICATION FOR 54.5% OF OUR
PATIENTS AND OTHER INDICATIONS
FOR APHERESIS HAD PRIAPRISM.
SO THE FIRST FIRST OBJECTIVE WAS
TO DETERMINE IF THESE PATIENTS
WHO WERE UNDERGOING CHRONIC RED
CELL EXCHANGE IN GOOD STEADY
STATE WHETHER THE PATIENTS STILL
HAD ACTIVATED NEUTROPHILS.
WE DREW WHOLE BLOOD FROM THE 22
PATIENTS AS WELL AS WHOLE BLOOD
FROM 22 AGE AND SEXED MATCHED
HEALTHY CONTROL AND INCUBATED
WITH BUFFER TO MIMIC SPONTANEOUS
DEGRANULATION OR THE BACTERIAL
PEPTIDE DMLF OR LPS AND MEASURED
DEGRANULATION RESPONSES.
FOR ALL CONDITIONS TESTED,
NEUTROPHILS FROM SICKLE CELL
PATIENTS RELEASED MORE MMP9 AND
DEGRANULATING TO A HIGHER
EXTENT.
THE RESULTS SHOW THE PATIENTS
RECEIVING CHRONIC RED CELL
EXCHANGE HAD RESPONSES COMPARED
TO HEALTHY CONTROLS.
SO NEXT WE WANTED TO KNOW IS
HEIGHTENED DEGRANULATION
RESPONSE REFLECTIVE OF
LEUKOCYT
LEUKOCYTOSIS.
WE PLOTTED AGAINST WHITE COUNT
SHOWN ON THE LEFT GRAPH OR
ABSOLUTE NEUTROPHIL COUNT ON THE
RIGHT HAND GRAPH.
THERE WAS NO CORRELATION BETWEEN
DEGRANULATION RESPONSES
SUGGESTING THE RESPONSES WE
OBSERVED ARE NOT SIMPLY DUE TO
CELL COUNT.
S TO LOOK AT THE EFFECT OF RED
CELL WE LOOKED AT BEFORE AND
AFTER RED CELL EXCHANGE AND
INCUBATED WITH BUFFER AND FLMP
OR LPS AND IT CAUSED A DECLINE
IN DEGRANULATION FOR ALL
AGONISTS TESTED.
SO AFTER MAKING THAT OBSERVATION
WE WANTED TO KNOW IF IT WAS
POSSIBLE THAT THE APHERESIS
APPARATUS WAS CONTRIBUTING TO
THIS OBSERVATION.
SO WE DECIDED TO RECRUIT A
CONTROL COHORT FOR OUR RED CELL
EXCHANGE STUDY COHORT.
SO WE CHOSE TO ENROLL FIVE
PATIENTS WITH NEUROLOGIC
DISORDERS UNDERGOING ROUTINE OUT
PATIENT PLASMA EXCHANGE.
THE REASON WE CHOSE THIS IS
BECAUSE THE PATIENTS WERE
UNDERGOING REGULARLY SCHEDULED
OUT PATIENT PROCEDURES.
THE PLASMA EXCHANGE USES THE
SAME APHERESIS EXCHANGE AS THE
RED CELL EXCHANGE AND USES THE
TUBING SET SO IT WOULD MIMIC
BLOOD CIRCULATING THROUGH THE
CIRCUIT.
AND IN THE LITTLE TABLE IS THE
DEMOGRAPHICS FOR THE FIVE
CONTROL PATIENTS.
WE HAVE ONE MALE AND FOUR MALE.
THE AVERAGE AGE WAS 46.2 YEARS
RANGING FROM 20 TO 61.
THREE PATIENT WITH DIFFERENT
CONDITIONS.
ON THE GRAPHS SHOWN TO THE RIGHT
WE PLOTTED THE SICKLE CELL
PATIENTS IN GREEN.
THESE ARE THE 22 PATIENTS WITH
SICKLE CELL DISEASE WHO ARE
UNDERGOING RED CELL EXCHANGE AND
PLOTTED THE FIVE PLASMA EXCHANGE
APPRECIATES IN GRAY.
YOU CAN SEE FOR ALL THE AGONISTS
TESTED IT CAUSED A DECLINE IN
CELL DE GRANULATION AND THE
PLASMA EXCHANGE PROCEDURE DID
NOT CAUSE A DEPARISHABLE DECLINE
IN RESPONSES.
THE FINDINGS SUGGEST THE
MODULATION OF DEGRANULATION IS
NOT JUST DUE TO BLOOD TRAVELLING
THROUGH THE SECTOR AND FLOWING
THROUGH THE TUBING.
SO BECAUSE OF PRIOR STUDIES HAD
SHOWN SS RED CELLS ARE ABLE TO
DIRECT RED CELLS AND WANTED TO
LOOK AT THE CORRELATION OF THE
DECLINE IN GRANULELATION WE WERE
OBSERVING.
WE PLOTTED DEGRANULATION
RESPONSES ON THE Y AXIS AGAINST
HEMOGLOBIN ON THE X AXIS.
YOU SEE FROM THE LEFT
SPONTANEOUS DEGRANULATION WAS
NOT SIGNIFICANTLY CORRELATED
WITH HEMOGLOBIN S LEVELS AND THE
RESPONSE TO LPS WAS STRONGLY
CORRELATED WITH HEMOGLOBIN
LEVELS AND IT SUGGESTS RED CELL
EXCHANGE MAY REMOVE CELLS AND
TRANSFUSE HEALTHY DONOR RED
CELLS.
THE LAST QUESTION WE WANTED TO
START TO TACKLE WAS HOW LONG IS
THE EFFECT OF RED CELL EXCHANGE.
ALL THE STUDIES I SHOWED YOU
WERE DONE ON BLOOD DRAWN PRIOR
TO RED CELL EXCHANGE AND AFTER.
WE WANTED TO SEE IF THERE WAS A
LONGER AFFECT OF RED CELL
ZHARCHK.
SO TO ANSWER THIS QUESTION WE
ENROLLED TWO PATIENTS AND
PERFORMED LONGITUDINAL STUDIES
AND HAD BLOOD DRAWN PRIOR AND
AFTER RED CELL EXCHANGE AND
AFTER DAY THREE AND DAY SEVEN
AND WEEKLY THEREAFTER FOR A
ONE-MONTH PERIOD.
ON THE TOP TWO GRAPHS ARE
DEGRANULATION TO PLA AND MLLF
AND YOU SEE THEY START TO
REBOUND AND GO BACK UP TO
BASELINE BY DAY SEVEN AFTER RED
CELL EXCHANGE AND FLUCTUATE AND
YOU SEE THE RESPONSES TO LPS AND
BUFFER.
YOU CAN SEE WITH LPS AND BUFFER
THE GRANULATION RESPONSE BUT
REMAIN DEPRESSED FOR A LONGER
PERIOD OF TIME AND DON'T START
TO REBOUND BACK TO BASELINE
UNTIL SOMEWHERE BETWEEN DAY 21
AND DAY 28.
IN THE BOTTOM TWO PANELS WE
PLOTTED THE PATIENTS WHITE
COUNT, ABSOLUTE NEUTROPHIL COUNT
AND HEMOGLOBIN LEVELS AT THE
STUDY TIME POINTS.
THE RESULTS TOGETHER SUGGEST
THAT RED CELL EXCHANGE HAS A
SUSTAINED EFFECT ON NEUTROPHIL
DEGRANULATION BEYOND THE
IMMEDIATE POST-PROCEDURE PERIOD.
THE NEXT QUESTION IS WHAT IS
CAUSING THE DEGRANULATION WITH
RED CELL EXCHANGE.
THIS IS SOMETHING OUR GROUP IS
INVESTIGATING.
AS A FIRST ATTEMPT FOR MECHANISM
WE FOCUSSED ON THE EXPOSURE.
ON THE LEFT GRAPH HEALTHY DONOR
NEUTROPHILS WERE INCUBATED WITH
RED CELLS IT CAUSED HEALTHY
NEUTROPHILS TO DEGRANULATE AND
CELLS THAT HAD INCREASED SS
EXPOSURE CAUSED A GREATER
INCREASE IN DEGRANULATION.
BUILDING ON THE RESULTS IN THE
RIGHT GRAPH WE THEN MEASURED PS
EXPOSURE ON CIRCULATING RED
CELLS AND SICKLE CELL PATIENTS
BEFORE RED CELL EXCHANGE AND
AFTER.
AND YOU CAN SEE THERE WAS AN
OVER ALL DECLINE IN PS EXPOSURE
WITH APHERESIS.
IN SUMMARY, RED CELL EXCHANGE
MODULATES RESPONSE AND DECLINE
IN HEMOGLOBIN S LEVELS AND THE
AFFECT OF RED CELL EXCHANGE IS
SUSTAINED OVER SEVERAL DAYS.
PS EXPOSURE INDUCES NEUTROPHIL
DEGRANULATION AND EXPOSURE
DECLINES WITH RED CELL EXCHANGE.
OUR FINDINGS RAISE THE
POSSIBILITY THAT TRADITIONAL RED
CELL EXCHANGE END POINTS MAY BE
INADEQUATE TO ASSESS THE
EXCHANGE AND THE FUNCTIONAL END
POINTS TO DEMONSTRATE ACTIVATION
MAY BE BENEFICIAL.
AS I EXPLAIN WHAT AMONG
MODULATES IS UNCLEAR AND IT'S
ONE MECHANISM DECREASING
NEUTROPHIL ACTIVATION AND
ONGOING STUDIES IN OUR LAB ARE
FOCUSSING ON ADHESION RECEPTORS
ON SS RED CELLS AND THE
INHIBITOR BY WHICH RED CELLS
TRANSFUSION MAY BE MODULATING
NEUTROPHIL ACTIVITY.
FUTURE STUDIES ARE STILL NEEDED
TO ESTABLISH THE MULTIPLE
MECHANISMS BY WHICH RED CELL
EXCHANGE DETERMINE INHIBITION
CAN BE INCORPORATED AS THE
THERAPEUTIC END POINT FOR RED
CELL EXCHANGE.
I WANTED TO TAKE A MINUTE TO
ACKNOWLEDGE THE MEMBERS OF MY
LAB FOR THE STUDIES I EXPLAINED
AND WANT TO THANK MY
COLLABORATORS AND MENTOR
DR. HELEN AND MEMBERS OF HER LAB
WHO PERFORMED ADHESION ASSAYS
AND THE SERRIN ASSAYS AND OF
COURSE OUR PATIENTS THAENDZ
APHERESIS NURSES.
GOOD AND THE APHERESIS NURSES.
THANK YOU.
>> THANK YOU.
>> DID YOU LOOK AT RETICULOCYTE
COUNT OR HEMOGLOBIN S TO COMPARE
>> CAN YOU SEE AT THE
FORMULATION.
>> I DID NOT LOOK AT THE OTHER
FRACTIONS SO THAT'S A FANTASTIC
IDEA.
>> WE HAVE A QUESTION ONLINE.
SHE'S ASKING GREAT STUDY ARE
THERE PLANS TO LOOK AT THIS PRE
AND POST TRANSFORMATIVE
THERAPIES AS WELL?
>> SHE ASKED ARE THERE PLANS TO
LOOK AT THIS PRE AND POST
TRANSFORMATIVE THERAPIES AS
WELL.
>> TRANSFORMATIVE THERAPIES?
>> YES.
>> OH, THAT WOULD BE FANTASTIC
TO DO.
I DID NOT THINK ABOUT THAT BUT
THAT WOULD ALSO BE VERY VERY
INTERESTING.
>> ANOTHER QUESTION FROM MARK
WALTERS.
ANY IDEA WHAT THE CALCIUM
EXPOSURE IN THE APHERESIS HAS ON
ACTIVATION?
YOUR DATA WERE A BIT AMBIGUOUS.
HE MEANT CO2 CALCIUM DEPLETION.
>> CALCIUM DEPLETION?
>> YES.
>> THE WHOLE BLOT IS NOT DRAWN
FROM THE APHERESIS CIRCUIT.
THE BLOOD FROM THE PATIENT IS
DRAWN FROM THE PATIENT'S BODY
FROM THEIR CENTRAL LINE OR
PERIPHERAL IVs.
NOT NOT DRAWN FROM THE APHERESIS
CIRCUIT AND THEY'RE DRAWN FROM
THE PRE-PROCEDURE LAB AND NOT
DRAWN FROM THE APHERESIS TUBING.
>> NO MORE QUESTIONS ONLINE.
LET'S MOVE ON TO THE NEXT
PRESENTATION THIS IS ONE FROM
UPDATE FROM ASH REGISTRY
COLLABORATORS ON SICKLE CELL
DISEASE NET WORK APPROACH TO
DEVELOPING DATA QUALITY IN LARGE
NATIONAL REGISTRIES AND GOING TO
BE PRESENTED BY DR. ALEXIS
THOMPSON OF CHILDREN'S HOSPITAL
OF PHILADELPHIA AND DR. TED WUN
FROM U.C. DAVIS.
ALEXIS.
>> GOOD AFTERNOON AND THANK YOU
FOR THE OPPORTUNITY TO UPDATE
THE AUDIENCE ON WORK BEING DONE
BY THE ASH RESEARCH
COLLABORATORS ON THE SICKLE CELL
NETWORK.
SO WHO ARE WE?
I HOPE MANY ARE FAMILIAR WITH
THE RESEARCH COLLABORATIVE.
IT WAS DESIGN TO IMPROVE THE
LIVES OF THOSE LIVING WITH BLOOD
SUPPORTERS BY SUPPORTING
COLLABORATIVE PARTNERSHIPS TO
FACILITATE RESEARCH AND
ULTIMATELY HOPEFULLY IMPROVE
PATIENT CARE.
CURRENTLY THE DATA HUB IS
CAPABLE OF INGEST ING DATA FROM
A VARIETY OF SOURCES BUT OUR
PRIMARY FOCUS HAS BEEN ON THE
WHOLE EMR FROM PARTICIPATING
INSTITUTIONS.
ONCE IN THE DATA HUB WE SEE THE
OPPORTUNITIES FALL INTO TWO
CATEGORIES.
ONE TO ENHANCE CLINICAL CARE BY
SUPPORTING THINGS LIKE
IDENTIFYING GAPS AND VARIABILITY
IN PATIENT CARE ALLOWING THE
INDIVIDUAL SITES TO USE THE DATA
HUB PORTAL TO BE ABLE TO SEE IN
REAL TIME NEAR REAL TIME THE
STATUS OF THEIR PATIENTS.
BUT TO BE ABLE TO ESSENTIALLY
LOOK AT USING THAT FOR ENHANCING
BEST PRACTICES.
WE ALSO SEE THE DATA FROM THE
DATA HUB BEING USED FOR RESEARCH
IN CREATING CONTEMPORANEOUS
CONTROL GROUPS POTENTIALLY FOR
POST-MARKET SURVEILLANCE,
SUPPORTING
INVESTIGATOR-INITIATED TRIALS
AND THE POTENTIAL FOR COHORT
IDENTIFICATION FOR PROSPECTIVE
STUDIES.
THIS IS WHERE WE ARE TO DATE AND
HAVE GROWN SINCE WE WERE LAST
YEAR.
WE HAVE A TOTAL OF 42 CONTRACTS
EXECUTED THAT MAKE UP A TOTAL OF
52 SITES REPRESENTED.
AND THESE 52 SITES USE A VARIETY
OF DIFFERENT SOURCES IN TERMS OF
THEIR ELECTRONIC HEALTH RECORD
VENDOR WITH THE PREDOMINANT
BEING EPIC AND THE DATA
SUBMISSION TAKES MORE THAN ONE
PATHWAY WITH THE MOST COMMON
ONES BEING OMOP OR FIRE API.
OF THE 56 SITES REPRESENTED,
SOME ARE IN VARIOUS POINTS WITH
SOME BEING IN THE TEST PHASE
OTHERS MOVING TOWARDS PRE TEST
BUT ABOUT 20 OF THEM NOW BEING
IN FULL PRODUCTION AND THEREFORE
READILY SUBMITTING DATA AT LEAST
QUARTERLY.
THIS REPRESENTS ABOUT 25,000
INDIVIDUALS WITH SICKLE CELL
DISEASE.
THERE ARE ALSO ABOUT 12 SITES
WHO HAVE ACTUALLY UNDER GONE AN
ADDITIONAL EFFORT THAT INVOLVES
WHAT WE CALL INVESTIGATOR
VERIFICATION OF SICKLE CELL
DIAGNOSIS.
THIS IS ATTESTATION BY THE SITE
P.I. USING EXISTING SOURCE DATA
TO VERIFY FROM THEIR PERSPECTIVE
THE DIAGNOSIS AND THIS IS
COMMONLY FROM INTERNAL
REGISTRIES.
SOMETIMES WORK IN COLLABORATION
WITH OTHER DATA INITIATIVES,
PROBLEM LIST AND CLINIC NOTES
AND ABOUT OVER 11,000 PATIENTS
HAVE NOW BEEN VERIFIED IN TERMS
MUCH THEIR DIAGNOSIS.
WE HAVE DONE WORK AS THE DATA
HUB AS IT INTERFACES WITH THE
CLINICAL TRIALS DATA HUB AND
DR. WUN WILL UPDATE YOU AS WELL.
>> THANK YOU, ALEXIS.
I'VE BEEN LEADING THE TEAM AND
AND IN THE APPROACH OF THIS I
FIRST AND SOMEONE TOLD ME ONE
TIME WE UNDERSTAND WHAT THE DATA
AS SCIENTISTS AND THE
INFORMICIST AND I WAS HONORED
AND THOUGHT IT WAS A GREAT
OPPORTUNITY TO CREATE A RESOURCE
WHICH I THINK WILL SERVE OUR
COMMUNITIES AND INCLUDING OUR
PATIENTS WELL.
THIS IS HIGHLIGHTING THE
RE-ORGANIZATION OF THE ASH
RESEARCH COLLABORATIVE WITH THE
BOARD OF DIRECTORS.
THE LEADERSHIP TEAM CONSISTS OF
THE CHAIRS, WHICH IS MYSELF AND
THE DATA QUALITY TEAM AND THREE
COMMITTEES ON THE BOTTOM,
SCIENTIFIC COMMITTEES, AMANDA
BRANDOW AND THE NATIONAL
COMMITTEE IS LED BY BAYLOR.
WE'LL BE ABLE TO STEER THE OVER
ALL DIRECTION OF THE PROGRAM AS
WELL AS IMPLEMENT THE DESIRES OF
THE BOARD OF THE DIRECTORS AND
AGAIN OUR CONSTITUENCIES AND I I
WILL CONVENE THE TEAM AND THEY
WERE SELECTED BECAUSE OF THEIR
EXPERIENCE AS CLINICIANS AND
DEALING WITH SOME YOU MAY NOT
RECOGNIZE SOME HAVE DONE LARGE
PROJECTS INCORPORATING DATA FROM
MULTIPLE INSTITUTIONS AS WELL AS
ONE PERSON BEING A LITTLE
PAROCHIAL WHO IS A CARD CARRYING
CLINI
CLINICAL INFORMATIST AND WHAT
WITH WANT TO BE AS A REGISTRY
AND RESEARCH COLLABORATIVE DATA
SOURCE IS TO PROVIDE DATA THAT
IS TRUSTWORTHY OF RESEARCHERS
FOR DATA QUALITY EFFORT AND
THAT'S OUR JOB IN THE RESEARCH
COLLABORATIVE IN GENERAL IS FOR.
SO WE'RE PUTTING TOGETHER A
REGIME.
AND THERE'S A BEEN DATA QUALITY
CHECKS THAT HAVE GONE INTO AFTER
INGESTION.
THE FIRST IS FOR COMPLETENESS.
AGAIN, DATA SCIENTISTS AND THE
REAL STATISTICIANS AND
EPIDEMIOLOGISTS I'VE WORKED WITH
OVER THE LAST COUPLE DECADES
TOLD ME YOU NEED TO KNOW YOUR
DATA.
SO I LOOK AT A LOT OF SPREAD
SHEETS WITH MY ANALYSTS SO I
KNOW MY DATA.
EVERY DATA SET HAS MISSINGNESS
AND ELEMENTS THAT ARE NOT CLEAR
AND IT'S IMPORTANT TO KNOW THAT.
THE SECOND IS CONSISTENCY.
THIS VARIES OVER TIME.
FOR WHATEVER REASON JUST LIKE
ALL THE THINGS WE DO IN OUR
CLINICAL LIVES, THE COMPLETENESS
OF THE DATA, THE QUALITY OF THE
DATA MAY CHANGE OVER TIME
BECAUSE OUR SOURCE IS SHIFTING.
THOSE OF YOU WHO HAVE GONE
THROUGH I DON'T KNOW HOW MANY
UPGRADES OF EPIC HAVE LIVED
THROUGH THIS YOURSELF.
SO WE NEED TO MAKE SURE AS WE
CONTINUE TO INGEST DATA FROM
OUR VARIOUS SOURCES IT'S
CONSISTENT AND WE ADJUST IF IT'S
NOT AND A BIG ONE WE WENT
THROUGH IS IN THE STATES
RECENTLY WAS ICD TO ICD10 AND
IT'S DIZZIESING -- DIZZYING
THINGS BACK AND FORTH AND I'VE
BECOME APPRECIATIVE OF THE
PEOPLE THAT DO THAT NOW AND WE
WANT IT ACCURATE.
DR. THOMPSON IS LEADING A
VALIDATION PROJECT AND WE HAVE
AN AN INVESTIGATOR ATTESTATION
TO THE DIAGNOSIS BUT THERE'S A
FOLLOW ON PROJECT THAT HAS BEEN
SUBMITTED AS AN ABSTRACT WE
WON'T DISCUSS NOW OF DOING AN
ANNUAL VALIDATION OF FORCED
DOCUMENTATION.
WE'RE WORKING ON A QAQC PLAN
THROUGH THE DATA CYCLE FROM
INGESTION TO INITIAL REGISTRY TO
TRANSFORMATION TO A DATA
WAREHOUSE TO CREATION OF
ANALYTICAL DATA SETS.
EACH STEP ALONG THE WAY WHAT
I'VE LEARNED FROM MY MENTORS AND
COLLABORATORS AT CALIFORNIA
CANCER REGISTRY IS EACH STEP
NEEDS A QAQC STEP TO MAKE SURE
THE DATA IS SOUND.
TO GIVE A TASTE OF WHAT'S THERE
THIS IS THE ACCUMULATED REGISTRY
NOW CLOSE TO 23,000.
WHAT THE YEARS REPRESENT ARE
UNIQUE ENCOUNTERS.
IT COUNTS THE YEARS OF DIAGNOSIS
NOT VALIDATE AND VERIFIED
DIAGNOSIS OF INDIVIDUALS THAT
HAVE HIT THE VARIOUS
CONTRIBUTORS OF THE DATA IN THAT
YEAR AND THAT'S WHY THE NUMBERS
YOU CAN'T SIMPLY ADD THEM UP BUT
CUMULATIVELY HERE'S THE PATIENTS
TO DATE.
HERE'S A TASTE OF THE DATA
AVAILABLE.
AS YOU KNOW THERE'S DISCHARGE
DATA WITH DIAGNOSES FROM EACH
ENCOUNTER FOR EMERGENCY ROOM
DEPARTMENT, ETCETERA AS WELL AS
PROBLEM LIST.
THIS IS A COMPILATION OF THE
COMORBIDITIES OR COMPLICATIONS
NA HAVE BEEN ENUMERATED SO FAR
IN ADULT AND PEDIATRIC PATIENTS
CUT OFF BEING 18.
THIS HAS NOT GONE THROUGH
VALIDATION YET.
THIS IS FACE VALIDITY.
SOME NUMBERS RING TRUE IN OUR
CLINICAL EXPERIENCES.
MY OWN GROUP PUBLISHED ON
EMBOLISM.
WHAT HAS BEEN COMMENTED SO FAR
BY PEOPLE IN PERSONALLY IS THE
ESSENTIAL HYPERTENSION NUMBER
SEEMS TO BE HIGH.
I WILL SAY HOWEVER THAT IN OUR
OWN STATE DATA WE WENT THROUGH
ACCUMULATIVE INCIDENTS EXERCISE
TO DO A PARTICULAR ANALYSIS WITH
OUR STATE DATA FROM 91 -- 1991
TO 2018 AND IT DEPENDS ON AGE
BECAUSE WE USAGE SCALE FOR
ACCUMULATIVE INCIDENTS.
I DON'T THINK THE NUMBERS ARE
THAT FAR OFF.
IT'S A HOPE AS WE CAN USE
EXTERNAL SOURCES TO VALIDATE AS
WELL AS INTERNAL VALIDATION.
AND THIS IS NOW ONE OF THE
THINGS AS WE KNOW SINCE ONE OF
THE ORIGINAL COHORT STUDIES
WE'VE ALL BEEN LOOKING IN THE
FIELD IS A LONGITUDINAL COHORT
WE CAN FOLLOW.
THIS IS SHOWING THOUGH IT'S LEFT
HEAVY RIGHT NOW, RIGHT
TRUNCATED, IS THE NUMBER OF
YEARS OF FOLLOW-UP ON INDIVIDUAL
PATIENTS AND AS TIME GOES ON THE
RIGHT SIDE IS GOING TO GROW
WHICH WILL BE A FANTASTIC
RESOURCE AND YOU CAN ALSO SEE
FROM THE AGE BANDS WE'RE GOING
TO FINALLY COLLECT MORE AND MORE
INFORMATION ON THAT GREATER THAN
30, GREATER THAN 45,
50-YEAR-OLDS.
I HAVE AN 81-YEAR-OLD HEMOGLOBIN
SC PATIENT NOW IN MY PATIENT
PANEL.
AS PATIENTS AGE WE'LL HOPEFULLY
CREATE MORE ON THE PATIENTS.
AND FINALLY FOR ME WE'RE WORKING
IN EARNEST ON CREATING
PHENOTYPES AND WE'LL BE
SOLICITING INPUT FROM OUR
VARIOUS COLLABORATORS AND
PARTNERS ON ONE PHENOTYPES TO
BUILD AND SECONDARILY FOR
VALIDATION AND WHETHER THE
PURPOSE IS FOR QI OR RESEARCH OR
CLINICAL TRIALS WITH CREATE
ALGORITHMS TO FIND US THE RIGHT
PATIENTS ACCURATELY AND QUICKLY.
THAT'S ANOTHER STEP THAT THE
WHOLE GROUP NOT JUST THE QUALITY
GROUP WILL BE WORKING ON IN THE
FUTURE.
I'LL LAND IT BACK TO
DR. THOMPSON.
>> THANK YOU, TED.
AND WANTED TO SHOW YOU WE'RE
BEGINNING TO SOLICIT AND SUPPORT
DATA PROJECTS AND INVESTIGATOR
INITIATED STUDIES THROUGH THE
CLINICAL TRIALS NETWORK AS WELL
AS THE DATA HUB.
WE'RE NOW FINISHING THE THIRD
ROUND OF PROPOSALS WITH FOUR
CONCEPTS HAVING WITHIN LAUNCHED.
TWO LEADING TO NIH SUBMISSIONS.
WE HAD A SECOND ROUND OF
CONCEPTS AND THE THIRD ROUND
JUST COMPLETED.
AND SEVERAL OF THESE WILL
INVOLVE REQUESTS DIRECTLY FROM
THE DATA HUB.
SO WE'RE VERY EXCITED ABOUT THE
ABILITY TO SEE THIS AMAZING
RESOURCE ALREADY BEING PUSHED
OUT AND THERE ARE A NUMBER OF
ABSTRACTS SUBMITTED TO THE
ANNUAL MEETING THIS YEAR USING
DATA FROM THE DATA HUB.
THERE'S ALSO A NUMBER OF
PUBLICATIONS ACTUALLY WITH THE
DATA HUB OR THE RESEARCH
NETWORK.
SO OUR HOPE IS FOR THOSE WHO ARE
MEMBERS OF THE CLINICAL TRIALS
NETWORK, YOU AS A P.I. OR EVEN
IF YOU'RE AN INTERESTED PERSON
AT AN INSTITUTION PART OF A
NETWORK YOU SHOULD FEEL FREE TO
COLLABORATE WITH YOUR
REPRESENTATIVE TO GET YOUR
INTEREST KNOWN OR REACH OUT TO
US.
WE'RE INTERESTED IN HEARING
FEASIBILITY ASSESSMENTS,
REVIEWING AND APPROVING PROTOCOL
WHEN LOOKING FOR COLLABORATORS
OR IF YOU HAVE AN IDEA AND WOULD
LIKE TO FUN IT UP THE FLAG POLE
OR WOULD LIKE TO USE DATA HUB
DATA.
THIS IS THE ADDRESS YOU CAN
CONTACT US FOR MORE INFORMATION.
THANK YOU.
>> I BELIEVE IN THIS AND HOPING
TO WORK WITH IT ONGOING.
ONE IS WHERE DO YOU FIND THE
DATA TO MAKE SURE YOU'RE GETTING
US SUCKED INTO THE RIGHT PLACE.
HOW MUCH ARE YOU WITH THE LARGE
GROUP ABLE TO TALK TO EPIC ABOUT
DESIGNING THEIR SICKLE CELL
INFORMATION COLLECTION TO FIND
IT IN A REASONABLE PLACE?
>> SO THAT CONVERSATION HAS
STARTED.
WE HAVE ALSO BEEN EXCITED ABOUT
DISCUSSIONS WITH THE OFFICE AT
THE NATIONAL COORDINATOR FOR
HEALTH INFORMATION TO BE ABLE TO
IDENTIFY CONSISTENTLY HOW WE
WILL DEFINE SICKLE CELL IN ANY
DATA SET AND THOSE CONVERSATIONS
HAVE STARTED MOVING BEYOND EPIC
AND WHAT NATIONAL STANDARDS WE
CAN PUT IN PLACE IN SICKLE CELL
AND EXCITED ABOUT BEING PART OF
THAT AS ARE OTHERS IN THE ROOM.
WE THINK THAT WILL BE ONE PLACE
WHERE IT STARTS.
FOR THOSE WHO ARE PART OF THE
CLINICAL TRIAL NETWORK, EACH ONE
HAS BEEN GIVEN ACCESS TO A
PORTAL AND THE INDIVIDUAL
PATIENTS' DATA IS INGESTED EVERY
QUARTER AND THAT DATA INCLUDING
THE DELINEATION OF THE SUB TYPES
OF SICKLE CELL DISEASE THERE'S
TWO LINES.
TYPICALLY YOUR DATA AND THE
AGGREGATE FOR THAT POINT IN
TIME.
FOR THE DATA HUB AS A WHOLE.
SO CERTAINLY FOR MY INSTITUTION
I'M ABLE TO LOOK AT COMPARING
THINGS LIKE E.D. TREAT AND
RELEASE AND HYDROXYUREA USE AND
COMORBIDITIES TED MENTIONED AND
BEING ABLE TO SEE THOSE AND ASK
THAT LOOK LIKE WHAT I THINK I
HAVE AND BEING ABLE TO TALK TO
THE STAFF HAS BEEN TERRIFIC IN
TERMS OF MY UNDERSTANDING THE
DATA AND THEN ALSO UNDERSTANDING
MY OWN PATIENT POPULATION.
>> HI, MEDICAL COLLEGE OF
WISCONSIN.
ARE YOU DOWNLOADING DISCREET
DATA OR USING LARGE LANGUAGE
MODELS TO MINE CLINICAL NOTES,
ETCETERA?
>> HASN'T COME UP YET, MARY BUT
IT'S A GREAT POINT.
RIGHT NOW WE'RE USING DISCREET
DATA BUT WE RECOGNIZE THERE'S A
NUMBER OF OBSERVATIONS IN SICKLE
CELL DISEASE THAT WILL NOT BE
INDIVIDUAL DATA ELEMENTS.
WE'VE ALREADY BEEN DISCUSSING
WHETHER IT'S NATURAL LANGUAGE
PROCESSING OR MACHINE LEARNING
TO BE ABLE TO UTILIZE THOSE NEW
TECHNOLOGIES TO BE ABLE TO PULL
DATA.
WE'D ALSO EVENTUALLY LIKE TO
LOOK AT PATIENT-REPORTED
OUTCOMES.
BEING ABLE TO LOOK AT HOW WE
TAKE OUR PLATFORM AND ARE ABLE
TO LOOK AT VALIDATED --
HOPEFULLY VALIDATED PRL TOOLS --
>> MAYBE WE SHOULD TALK SOME
TIME.
BUT THE OTHER WHAT INCIDENTS
DEPEND ON WHERE YOU PULL IT FROM
AND HOW YOU DEFINE IT.
THAT'S DIFFERENT FROM SAYING WAS
THERE A HYPERTENSION MEDICATION.
DO YOU KNOW HOW THOSE INCIDENTS
WERE GENERATED?
>> SO I'LL TELL YOU A COUPLE
THINGS.
ONE IS I DIDN'T MENTION THE
DETAILS OF THE DIFFERENT
PROJECTS IN TERMS OF WHAT WE
AGREED TO SUPPORT.
SEVERAL ARE ASKING THE KIND OF
QUESTIONS YOU'RE ASKING ABOUT
VERY SPECIFIC SUB POPULATIONS OF
PATIENTS.
SO WHETHER IT'S LOOKING AT CKD
OR PAIN OR AKI BUT LOOKING AT
DIFFERENT MODELS ON HOW ONE
ACTUALLY DRILLS DOWN ON
ASSESSMENTS IN THOSE DIFFERENT
AREAS OF COMORBIDITIES.
THAT'S WHAT SOME OF THOSE EARLY
REQUESTS WERE.
>> THANK YOU.
>> TO ELABORATE ON THAT, I THINK
FOR NOW WHAT HAS BEEN DONE IS A
STRUCTURED DATA ELEMENT.
THERE IS A CAPABILITY AND THE
NOTES HAVE BEEN INGESTED.
THERE'S A CAPABILITY THEY'RE
WORKING ON TO LOOK FOR THOSE
OTHER THINGS AND THEN I THINK
THE PHENOTYPE THAT'S GOING TO BE
FOR ME INTELLECTUALLY THE MOST
INTERESTING PART IS USING A
COMBINATION OF STRUCTURED DATA
OF THINGS YOU GET FROM THE NLP
TO CHANGE TO STRUCTURED DATA AND
PRESCRIBING AND DISPENSING
INFORMATION TO SAY YOU ONLY
COUNT HYPERTENSION IF IT'S
MENTIONED THREE TIMES AND GIVEN
THE HYPERTENSIVE MEDICINE OR
WHAT THE MEDICINES ARE.
>> THE DATA IS CONSIDERING.
I'M SYMPATHETIC TO THE PROCESS.
>> BUT THEN AGAIN INGEST ING
DIFFERENT TYPES OF DATA AS WITH
OTHER CONSOLIDATED DATA
WAREHOUSES AS DR. THOMPSON
MENTIONED IS IMAGING DATA AND
SITES CAN DO IT WITH GEEM OMIC
DATA -- GENOMIC DATA.
>> CAN ANY CONSORTIUM JOIN?
>> WE HOPE SO.
WE'RE HOPEFUL THAT WE'RE GOING
TO CLEAR THAT WITHIN THE NEXT --
WE'RE HOPING THE NEXT 12 TO 18
MONTHS AND THEN WE'LL BE OPEN TO
RECEIVING MORE SITES THAT WOULD
BE INTERESTING.
THE QUESTION HAS ALREADY BEEN
RAISED ABOUT INTERNATIONAL.
I THINK THAT IS ABSOLUTELY
SOMETHING THAT WE WANT TO TALK
ABOUT.
>> FOR PRACTICAL PURPOSES SHOULD
I SEND AN E-MAIL TO PUT
OURSELVES ON THE WAIT LIST?
>> PLEASE.
>> I THINK THE PROCESS IS
BECOMING FASTER.
I KNOW WE'RE RUNNING OUT OF
TIME.
RIGHT NOW THOSE PARTICIPATING IN
MANY DATA INITIATIVES WHETHER
IT'S NCATS OR ALL THESE THINGS,
RIGHT NOW THERE HAVE BEEN MANY
COMPETING MODELS.
IT'S VERY DIFFICULT.
I THINK PEOPLE ARE NOW
AGGREGATING OR CONVERGING ON TO
A COUPLE THINGS.
FOR YOUR OWN I.T. DEPARTMENTS IT
WILL BECOME EASIER.
>> ANY QUESTIONS ONLINE?
NO QUESTIONS ONLINE.
THANK YOU SO MUCH.
>> THANK YOU.
>> OKAY.
MOVING ALONG WE HAVE NEXT TALK
IS FROM DR. VIVIEN SHEEHAN
IMPACT OF OSIVELOTOR ON BONE
MARROW AND STEM CELLS IN SICKLE
CELL MOUSE MODEL.
>> THANK YOU FOR ALLOWING ME TO
PRESENT.
MY APOLOGIES I CAN'T BE IN
PERSON.
I'M IN A HOTEL ROOM AND IT'S
BEEN A WONDERFUL MEETING AND
I'VE LEARNED A LOT.
SO I THINK MANY OF US ARE
FAMILIAR WITH OSIVELOTOR AND THE
SECOND GENERATION GBT 601 WE'LL
CALL 601 AND THE ABILITY TO
INCREASE THE OXYGEN AFFINITY
STABILIZING THE HEMOGLOBIN AND
THE OXYGENATED CONFIRMATION.
WHEN OSIVELOTOR BECAME AVAILABLE
THERE WAS A CONCERN OF HAVING
NEGATIVE EFFECTS ON THE VIROLOGY
OF BLOOD.
THAT'S WHEN I FIRST BECAME
INVOLVED IN THIS TYPE OF WORK
FEEDING THESE COMPOUNDING TO THE
SICKLE MOUSE MODEL.
THIS LED TO FUTURE WORK I'LL BE
PRESENTING.
IN THIS EXPERIMENT WE GAVE DRUG
CONTAINING CHOW AND STANDARD
CHOW TO A COHORT AND HAD A
COMPARATOR FOR SPECIFIC ASSAYS.
WE LOOKED AMOUNT THE EFFECT OF
DRUG CHOW COMPARED TO STANDARD
THE CBC USING EXOCYTOMETRY AND
IMAGED THE BLOOD FLOW AND LOOKED
AT RETICULOCYTE COUNT.
IT'S PROBABLY NO SURPRISE THAT
GBT 601 INCREASES HEMOGLOBIN.
IT'S USED TWO DOSES IN MANY
ASSAYS, .2% AND .4% OF NOTE THE
CLINICAL TRIAL USES THE HIGHER
DOSE OF .4%.
AND THERE'S A HEMOGLOBINOPATHY
TO NORMALIZING WITH THE .4% AND
REDUCTION IN RETIC COUNT WHICH
DID NOT ACHIEVE STATISTICAL
SIGNIFICANCE.
NEXT WE WRAVENTED TO LOOK AT THE
-- WANTED TO LOOK AT THE IMPACT
OF RED CELL DEFORMITY AND
POLYMERIZE AND UNDER HYPOXIA.
AND WHAT USES EXOCYTOMETRY AND
YOU PUT THIS IN THE SOLUTION AND
IT'S SUBJECTED TO HYPOXIA AND
THE SHAPE IS ANALYZED USING THE
LASER TO DETERMINE IF IT'S
SMOOTH OR MORE ANGLED WHEN
OXY
OXYGENATED OR MORE RIGID WITH
THE DEOXYGENATED.
601 IMPROVED THE RED CELL
DEFORMABILITY AND TOLERANCE.
THE RED CELL WAS LESS LIKELY TO
SICKLE INDICATING THE
DEPOLYMERIZATION OF THE MICE
TREATED WITH DRUG.
WE SAW THE RED CELL FLEXIBILITY
AND THE POINT OF SICKLING.
THE RED CELL WAS ABLE TO WITH
STAND SICKLING AT LOWER OXYGEN
LEVELS IN MICE TREATED WITH 601.
THE HEMOGLOBIN WAS REFERRED TO
THE ON DRUG NATIONAL STATE AND
POTENTIALLY HAVE HYPER VISCOSITY
EFFECT AND WE MET THE MICE WITH
THE GBT CHOW FLUID UP TO DAY
FIVE AND COMPARED IT TO THE MICE
WITH CONTROL CHOW.
YOU CAN SEE A FACT EFFECT AND
DISSIPATED WHEN THE CHOW WAS
WITHDRAWN.
YOU CAN SEE BY DAY THREE THE
HYPOXIA RETURNED BACK TO CONTROL
LEVELS AS IF IT WAS NEVER THERE.
THE EI BENEFITS WERE MAINTAINED
AND PRESENT THOUGH NOT
STATISTICALLY SIGNIFICANT BY DAY
FIVE.
THIS LED US TO CONSIDER WHAT IS
THIS DOING IMPROVING THE
NORMOXIC RED CELL SINCE WHAT THE
DRUG DOES IS ENCOURAGE THE RED
CELL TO STAY IN ITS NORMOXIC
CONFIRMATION.
I CAN'T SEE THIS EFFECT WHEN I
FED THE MICE WITH DRUG CHOW FOR
TWO WEEKS OR REQUIRED A MORE
PROLONGED TREATMENT OF SIX WEEKS
TO GET THE IMPROVEMENT IN THE
NORMOXIC RED CELL AND HAD A
REDUCTION IN V CAM AND AND WE
SAW IMPROVEMENT IN THE BONE
MARROW CELLULARITY IN THE BONE
MARROW.
WE'RE LOOKING AT THE POSITIVITY
WHICH IS A MARKER OF THE
APOPTOSIS AND WE SEE A REDUCTION
IN THAT WITH DRUG.
AND REDUCTION OF STRESS AND THE
MOUSE USES THE SPLEEN AS A SITE
OF ERYTHROPHERESIS AND WE SAW
MATURATION WITH DRUG CHOW.
AND REDUCTION OF APOPTOSIS OF
THE BLAST AND RETICK -- THE
SITES.
THE BEST PICTURE IS MISSING AND
I DON'T KNOW WHY.
WE HYPOTHESIZED THE LONG-TERM
BENEFIT THE IMPROVEMENT IN THE
NORMOXIC RED CELL WAS DUE TO AN
IMPROVEMENT IN THE BONE MARROW
AND LOOKED TO SEE WHETHER THE
STROMA SEEN IN THE MOUSE BONE
MARROW COULD BE IMPROVED BY
TREATMENT WITH 601.
YOU'LL HAVE TO TAKE MY WORD FOR
IT WE SAW NORMALIZATION OF THE
TORTURED BLOOD VESSELS OF THE
BONE MARROW AND NORMALIZATION OF
THE DISORDERED STROMA.
IT QUANTIFIED IN THE PANEL AND
MADE IT'S WAY THROUGH AND
THERE'S NO STATISTICAL
DIFFERENCE BETWEEN STROMA OF THE
A A MOUSE COMPARED TO THE 601
AND LOWER DOSE THAN IN THE
CLINICAL TRIALS CURRENTLY.
YOU CAN SEE THE MARK OF THE
BLOOD VESSELS AND AS THEY BEEN
LUNARIZATION OF THE BLOOD
VESSELS VERSUS THE CONTROL CHOW.
SEE THE SAME WITH THE
NORMALIZATION OF THE STROMA AS
MARK BY THE END.
SO WE CONCLUDE 601 INCREASES
HEMOGLOBIN AND AS THE CORRELATE
WITH IMPROVEMENT IN THE BONE
MARROW ENVIRONMENT AND WE WERE
HAPPY TO SEE THIS NORMALIZATION
OF THE PATHOLOGIC ANGIOGENESIS
IMPROVEMENT IN THE STROMA AND
THE CHANGES ARE TYPICALLY
ASSOCIATED WITH IMPROVED HSC
HEALTH AND THAT WORK IS ONGOING.
SO THIS IS A TIMELY FINDING AS
FOLKS HEARD WE HAD A WONDERFUL
TALK THE FIRST DAY OF THE
MEETING FROM DR. MARIN TALKING
ABOUT THE NEED TO IMPROVE OUR
CONTROL OF SICKLE CELL LEADING
UP TO MOBILIZATION FOR GENE
THERAPY.
WHAT I WANT TO PROPOSE IS A YEAR
LONG COURSE OF 601 PRIOR TO
GENE-BASED THERAPY TO IMPROVE
HSC HELP AND IMPROVE OUR ABILITY
TO MOBILIZE STEM CELLS AND
HOMING WILL IMPROVE THE
STRUCTURE OF THE BONE MARROW.
AS WE ATTEMPT TO CONVERT OUR
DATA FROM MOUSE TO HUMAN A YEAR
SEEMS TO BE SUFFICIENT AND THIS
COULD REPLACE THE LEAD UP TO
GENE THERAPY WHICH IS TIME
CONSUMING WHILE WE WAIT FOR
APPROVAL AND ASSESSMENT OF THE
PATIENT RATHER THAN HAVING THEM
BE TRANSFUSED AND HAVE AN ORAL
THERAPY WHICH COULD BE A GAME
CHANGER WITH THOSE DIFFICULT TO
MATCH BLOOD UNITS FOR.
HAPPY TO TAKE ANY QUESTIONS.
I WANT TO THANK MY WONDERFUL LAB
AT EMORY AND COLLABORATIONS THAT
TAUGHT ME ABOUT LORCA AND MY
COLLABORATORS AT GEORGIA TECH
AND FUNDING SOURCES.
QUESTIONS FROM THE AUDIENCE?
ANYTHING ONLINE?
>> I THINK IN HER PRESENTATION
THE QUESTIONS WERE ANSWERED.
>> THAT'S EFFICIENT.
SO I THINK WE'RE SUPPOSED TO
TAKE A BREAK NOW BUT I THINK
GIVEN THE LATENESS OF THE DAY AT
THIS POINT AND WE HAVE JUST ONE
MORE SESSION SO I'M HOPING AND
IS JULIE ONLINE WOULD YOU MIND
TAKING US ACROSS THE FINISH
LINE?
>> WILL DO.
>> SO WE'LL HAVE IT FINAL TALK
AND SCRIPT THE BREAK.
IF ANYBODY WANTS TO GET UP FOR A
BIO BREAK, PLEASE DO.
THIS IS GOING TO BE THE UPDATES
ON NATIONAL ALLIANCE OF SICKLE
CELL CENTERS INCLUDING CONSENSUS
RECOMMENDATION AND JULIE KANTER
AND HER GROUP WILL BE PRESENTING
MULTIPLE PRESENTATION.
>> YOU THANK YOU FOR THE
OPPORTUNITY TO PRESENT.
SORRY I'M NOT THERE IN PERSON.
AND WHY WE STARTED THE NATIONAL
ALLIANCE OF SICKLE CELL CENTERS
IN 2020 AND TALK WHERE WE ARE
NOW AND WHERE THE FUTURE IS
GOING AND IF ANYONE HASN'T YET
JOINED IN THE FUN WE WANT TO
INVITE YOU TO BECOME A MEMBER.
WE STARTED A NATIONAL ALLIANCE
IN 2020 AND NOTHING WAS GOING
ON, WE WERE ALL PANDEMIC AND
REALIZED THERE WASN'T AN
ORGANIZATION DEDICATED TO
PROVIDERS AND NOT JUST PHYSICIAN
AND RESEARCHERS BUT NURSES, CARE
COORDINATORS.
EVERYTHING WE NEED TO MAKE IT
BETTER FOR SICKLE CELL AND DON'T
HAVE THE OPPORTUNITY TO ENGAGE
TEAMS AND WE WANTED TO WORK ON A
WAY TO IMPROVE CARE OF SICKLE
CELL DISEASE AND FOCUS ON
CLINICAL AND QUALITY OF CAIRO
OPPOSED TO NOVEL THERAPEUTICS.
AND PROVIDE A FINANCIAL MODEL
FOR AFFILIATES AND WANTED TO
BUILD A COMMUNITY TO SUPPORT
SUSTAINABILITY.
WE ALSO RECOGNIZED WHERE WE
DON'T HAVE DATA AND THERE ARE SO
MANY PLACES WE DON'T HAVE DATA.
THERE'S MANY ELEMENTS OF
STANDARD OF CARE THAT HAVEN'T
BEEN VALIDATED OR PROVEN ON THE
POPULATION LEVEL.
THERE'S HUGE VARIATION IN
PROCESS AND IT SEEMS ANECDOTE
AND OPINION HAVE BEEN TRANSLATED
AND SOMETHING LIKE SICKLE STROKE
SCREENING THERE'S A HUGE GAP IN
CARE DELIVERY.
WHILE THERE'S BEEN WORK DONE ON
IMPROVING THE GAP THERE'S WAY TO
GO AND POLITICAL BOUNDARIES THAT
HAVE HAMPERED SUCCESS AND THE
NUMBER OF REGISTRIES THAT HAVE
COME AND GONE AND AMAZING GRANTS
THAT HAVE COME AND GONE WHERE
THE DATA AND KNOWLEDGE GETS LOST
BECAUSE IT'S NOT KEPT IN A
CONTINUED SPACE AND NEED TO MOVE
FORWARD WORKING TOGETHER.
IT DOESN'T STOP WITH GENE
THERAPY IN FACT IT SHOULD IGNITE
MORE AND WE HAVE A LONG TIME
BEFORE IT GETS TO GENE THERAPY
AND INDIVIDUALS WHO MAY NOT WANT
GENE THERAPY AND DEVELOPING IS
NOT ENOUGH.
WE NEED TO MAKE SURE THEY GET TO
CARE.
OUR PRIMARY GOAL IS TO ENSURE
AND IMPROVE ACCESS TO A SICKLE
CELL DISEASE SPECIALIST AND HOW
IT SHOULD BE A GOAL.
WE KNOW THE SYSTEM OF CARE IS
BROKEN ESPECIALLY IN THE UNITED
STATES.
WE ALSO KNOW THERE ARE THINGS WE
AS SPECIALISTS DON'T AGREE ON.
MY FAVORITE EXAMPLE IS HOW OFTEN
AN ECHO CARDIO GRAM BE DONE AND
I'VE SEEN FISTICUFFS EMERGE FROM
THAT AND WE CAN ANSWER QUESTIONS
EFFECTIVELY AND OUTCOMES HAVE TO
BE THE RESULT OF THE SYSTEM OF
CARE AND NOT JUST INDIVIDUAL.
WE WANT TO WORK TOGETHER TO
IMPROVE OUTCOMES.
WE HAVE ABOUT 98 SICKLE CELL
DISEASE CENTERS AND WE
OVERLAPPED AND THERE'S MANY IN
THE UNITED STATES AND YES WE
WANT TO GO TO CANADA TOO AND
THERE'S A PLAN FOR THAT.
IN THE MEANTIME I WANT TO SAY
THERE ARE MANY SICKLE CELL
CENTERS AND WE NEED TO HARNESS
WHAT WE'RE DOING AND WORK
FURTHER TOGETHER.
AND WE SAID WE'RE GOING TO
DEFINE THAT.
WE DID TWO STUDIES.
ONE FOR ADULTS AND ONE FOR
CENTER REQUIREMENTS.
AND MANY PEOPLE KNOW THERE ARE A
LOT OF HOSPITALS AND ACADEMIC
CENTERS UNWILLING TO INVESTIGATE
IN THE CARE OF PEOPLE WITH
SICKLE CELL DISEASE.
TO BE PART OF THE ALLIANCE IS
SOMETHING YOU COULD TAKE TO YOUR
CEO AND SAY HERE'S WHAT WE NEED
TO DO TO BECOME A MEMBER OF THIS
GROUP AND LOOK AT DATA DISCOVERY
AND WE TALKED ABOUT IT AND IT
INCLUDES 4,000 INDIVIDUALS AND
THEY HAVE FULL PHENOTYPES.
WE VOTED ON RECOMMENDATIONS AND
WE HELD THE THIRD ANNUAL SICKLE
CELL CENTERS MEETING AND HAD
OVER 200 PEOPLE FROM OVER 150
DIFFERENT INSTITUTIONS THE
MAJORITY OF WHICH WERE SICKLE
CELL CENTERS SO WE WERE EXCITED.
IN DEVELOPING RECOMMENDATIONS
WITH DEFINED TWO LEVELS.
ONE MET STANDARD.
WHAT PROVIDERS MUST DO TO ENSURE
SAFE AND ADEQUATE CARE AND WE
KNOW THESE THINGS ARE
BENEFICIAL.
SUCH AS THE IMPORTANCE OF GOING
TO THE DENTIST TWICE A YEAR FOR
ANNUAL CLEANINGS.
WITH KNOW PATIENTS NEED TO DO
THAT AND THERE'S LIMITATIONS AND
OTHER PROBLEMS.
WE CAN'T HOLD THAT AS A STANDARD
OF CARE.
AND THERE'S A SERIES OF
ITERATIVE SURVEYS AND COMPROMISE
AND THEN LEAD TO A VOTE WHERE
ALL CENTERS GET ONE VOTE LEADING
TO RECOMMENDATIONS WHERE IT HAS
TO BE OVER 70% TO BE CONSIDERED
A RECOMMENDATION.
WE'VE DEVELOPED PEDIATRIC AND
ADULT RECOMMENDATIONS TO UNDER
GO PEER REVIEW AND WE HAVE THE
TABLES OF THE RECOMMENDATIONS ON
THE WEBSITE.
YOU CAN PULL THAT UP AND
BASICALLY SAY WHAT DOES A
2-YEAR-OLD NEED OR 15-YEAR-OLD
OR 55-YEAR-OLD NEED?
WE TALKED ABOUT RECOMMENDATIONS
AND THOSE WILL BE ON THE WEBSITE
BY THE END OF THIS WEEK AND
DEFINED TRANSITION IN SICKLE
CELL DISEASE.
AND DR. GAURINO WILL TALK ABOUT
THAT AND PLANS SIMILAR TO WHAT
DR. TANABE DESCRIBED AND A
SOCIAL WORKER.
LET'S TALK ABOUT GRAN DAD AND
IT'S A PROSPECTIVE HIGH QUALITY
CURATED DATA SET TO IMPROVE AND
GUIDE ADHERENCE TO CARE AND
PROVIDE THE PLATFORM FOR QUALITY
IMPROVEMENT.
IT ALLOWS FOR REAL TIME
INVESTIGATION OF NOVEL THERAPIES
THOUGH THE MAY HAVE BEEN GOAL IS
QUALITY IMPROVEMENT AND USE IT
AS A REGISTRY AND USING GRAN DAD
FOR THE ALLIANCE AND FOR THE
SICKLE CELL DISEASE TDP PROGRAM
DEMONSTRATING HOW ONE CAN BE
USED IN DIFFERENT WAYS AND THE
DATA WON'T GO AWAY IF THE
PROJECT GOES AWAY.
ALMOST ANYTHING YOU COULD WANT
IS WITHIN GRAN DAD.
SUPPORT IS DEVELOPED BY OUR
PROGRAM INITIALLY AND MAKE SURE
WE SUSTAIN IT.
IT TOOK SUPPORT TO MAKE IT PART
OF THE ALLIANCE AND CONTINUES TO
BE A PARTNERSHIP BETWEEN THE TDP
PROGRAM.
AND RESOURCES AND TRAINING
PROGRAM.
IT OFFERED TRAINING FOR OUR APPs
AND NURSE PRACTITIONERS TO
BECOME A SPECIALIST IN SICKLE
CELL DISEASE AND THEY HAVE
SESSIONS DEDICATED FOR AVPs AND
HAVE AN OBSERVATION RUBRIC AND
HAVE TO DO CASE PRESENTATIONS
AND HAVE CHECKPOINT ASSESSMENTS
PRE AND POST TEST ASSESSMENTS
AND WILL BE AN OFFICIAL APP
FELLOWSHIP PROGRAM.
THIS WILL ALLOW US TO DEVELOP
AFFILIATE SITES AND WHAT WE CAN
DO FOR PHYSICIANS WHO DON'T
BECOME HEMATOLOGISTS BUT WANT TO
BECOME SICKLE CELL SPECIALIST.
FINALLY WANT TO TALK ABOUT
RECIPE.
IT'S AN NIH FUNDED GRANT LOOKING
TO HOW PATIENTS GOT UNAFFILIATED
FROM SICKLE CELL DISEASE CARE
AND WHY ARE SO MANY NOT SEEING
SPECIALISTS AN FIND THEM AND
RECRUIT THEM AND ENSURE THEY
HAVE BETTER OUTCOMES.
AS WE USE DATA WHEN THE PROJECT
IS OVER AND THE PROJECT GOES
AWAY, THEN WE'LL BE ABLE TO HAVE
THE DATA EMBEDDED IN GRAN DAD
AND IT WON'T GO AWAY WHEN THE
PROJECT GOES AWAY.
I DON'T KNOW IF MY SLIDES
DISAPPEARED FOR EVERYBODY OR
JUST ME.
WE HAVE THE CAPTURE POINT OF
TRANSITION.
WE HOPE TO PROVIDE EDUCATION NOT
JUST FOR PHYSICIANS BUT ADPs AND
NURSES AND SOCIAL WORKERS AND
HAVE AN ACTIVE GROUP OF SOCIAL
WORKERS WORKING TO PUT
GUIDELINES TOGETHER.
WE HAVE OUR 2025 MEETING IN
JULY, LOCATION TBD AND MORE
CENTERS JOINING AND HAVE OTHER
IMPROVED ACCESS TO POLICIES,
PROCEDURES AND PROTOCOLS
AVAILABLE TO MEMBERS.
WE HAVE OTHER RECOMMENDATIONS IN
PROJECT.
HOW TO TREAT IRON OVERLOAD AND
RECOMMENDATIONS ARE ALMOST 100%
COMPLETE AND EMPHASIS ON WHEN
SOMEONE SHOULD BE TRANSFERRED TO
A HOSPITAL THAT INCLUDES A
SPECIALIST AND DEFINING THAT
SICKLE CELL DISEASE SPECIALIST
AND THEY SHOULD BE COMING OUT
FOR FINAL VOTE IN THE NEXT
COUPLE MONTHS.
HOPEFULLY BY THIS TIME NEXT YEAR
WE'LL BE PUBLISHED.
WE FOCUSSED ON PALLIATIVE AND
CANCER MANAGEMENT IN PEOPLE WITH
SICKLE CELL DISEASE AND CBO
INTEGRATION.
WE STARTED THE DISCUSSION ABOUT
THE RIGHT PATIENT FOR GENE
THERAPY.
THAT'S A MORE COMPLEX
CONVERSATION WE PLAN FOR TWO
YEARS OF DISCUSSIONS BEFORE WE
MOVE IT BACK IN TO THE CONSENSUS
PLACE.
AND NOW I TAKE PLEASURE IN
INTRODUCING DR. LANZKRON A
PROFESSOR IN THE DIVISION HEAD
OF HEMATOLOGY AT THOMAS
JEFFERSON AND WILL TALK ABOUT
SOMEBODY IMPORTANT THAT'S BEEN A
CENTER POINT THE ANNUAL
COMPREHENSIVE CARE VISIT FOR
INDIVIDUALS WITH SICKLE CELL.
>> I'LL TALK WITH THE VISIT AT
OUR CONSENSUS MEETING AND HOW TO
INTEGRATE ACROSS DATABASES AND
USE IT TO IMPROVE CARE.
WE ALL KNOW PEOPLE WE SEE WITH
SICKLE CELL DISEASE IS
ASSOCIATED WITH SIGNIFICANT
MORBIDITY AND MORTALITY AND THE
GOAL OF THE VISIT IS TRYING TO
IDENTIFY THE RISK FACTORS AND
ACT UPON THEM WHEN THERE'S
EVIDENCE TO SUPPORT DOING THAT.
IT'S INTERESTING THE GENERAL
POPULATION AS A WHOLE NOT JUST
PEOPLE WITH SICKLE CELL DISEASE
AND RECOMMENDS AGAINST HEALTH
CHECKS FOR ASYMPTOMATIC ADULTS
AND THE PEOPLE WE TAKE CARE OF
ARE NOT ASYMPTOMATIC ADULTS FOR
THE GENERAL POPULATION THERE
SHOULD BE ANNUAL REVIEWS BECAUSE
THEY PROMOTE TRUST WITH
PHYSICIANS.
SO THE PREVIOUS SLIDES TALKED
ABOUT WHERE THERE WERE BENEFITS
FOR MORTALITY AND SOME HEALTH
BEHAVIORS IMPROVED WHEN YOU TWO
AN ANNUAL VISIT.
THERE'S NO DATA IN SICKLE CELL
DISEASE AND I LEARNED HOW I TAKE
CARE OF PEOPLE NOT FROM A
TEXTBOOK FROM MENTORS AND
THERE'S SOME DATA IN THE
GUIDELINES THE NHLBI GUIDELINES
NOW A DECADE OLD.
A LOT OF THIS IS NOT EVIDENCE
BASED AND VARIES ACROSS
INSTITUTIONS.
AS A SICKLE COMMUNITY TO IMPROVE
CARE WE NEED TO BUILD EVIDENCE
BUT CAN'T WAIT FOR THAT EVIDENCE
WE NEED THE ABILITY TO HELP US
DEFINE BEST PRACTICES.
WE HAVE TO MEASURE AND ANALYZE
DATA AGAINST IMPROVEMENTS.
SO YOU HEARD LATE ABOUT WHY
THEY'RE MAKING THE
RECOMMENDATIONS IT'S TO
FACILITATE PRACTICE
HARMONIZATION AND PRACTICE IN A
SIMILAR WAY ACROSS SITES.
CONSENSUS ON THE
RECOMMENDATIONS.
AND TO REINFORCE THE VOTING
PROCESS AND ARE ABLE TO AND THEN
WE HAVE VOTE AFTER DISCUSSION
ABOUT THE RECOMMENDATIONS AND
THE STANDARDS AND
RECOMMENDATIONS ARE SENT TO ALL
THE SITES AND THINGS ARE
INCLUDED AS A CONCENSUS
RECOMMENDATION ARE STANDARD IF
70% OF SITES AGREE.
THIS INCLUDED THE STANDARDS
GOING TO 81 FULL AND ASSOCIATE
SITE MEMBERS WHO VOTED ON THESE
RECOMMENDATIONS.
AND TO REMIND YOU FOR ALL THE
RECOMMENDATIONS WE BROKE THEM
DOWN TO STANDARD FOR SAFE AND
ADEQUATE CARE AND RECOMMENDED
ARE THOSE BENEFICIAL AND
PROVIDERS SHOULD PROBABLY TRY TO
FOLLOW FOR WHICH THERE'S LESS
EVIDENCE TO SUPPORT THEM.
AND SHOULD INCLUDE ACUTE CARE
USE AND TREATMENT SETTINGS AS
WELL AS HOSPITALIZATIONS AND
ANOTHER STANDARD IS HOW ADULTS
WITH SICKLE CELL DISEASE HAVE AN
ESTABLISHED PRIMARY CARE
PROVIDER AND PROVIDE SCREENING
IN ADDITION TO THEIR ITEMS I
WILL NOW DETAIL.
ALL ADULTS WITH SICKLE CELL
DISEASE SHOULD BE REFERRED TO
LOCAL OR NATIONAL SICKLE CELL
DISEASE ORGANIZATIONS FOR
SUPPORT IF AVAILABLE.
AS A RECOMMENDATION THOSE ON
MODIFYING THERAPY OR REQUIRE
PRESCRIPTIONS FOR OPIOIDS SHOULD
BE SEEN EVERY THREE MONTHS FOR
FOLLOW-UP AND ADULTS WITH MORE
MILD DISEASE PHENOTYPE EVERY SIX
MONTHS.
AND THE ANNUAL COMPREHENSIVE
HISTORY.
IT'S RECOMMENDED ALL ADULTS
RECEIVE THE STANDARD ANNUAL
VISIT WHICH I'M GOING TO GO IN
THE DETAILS FOR AND INTENSE BUT
IT'S IMPORTANT.
AGAIN ONE OF THE MAIN REASONS
DEVELOP TRUST AND IMPROVE THE
RELATIONSHIP AND HAVE COMPLEX
ILLNESSES AND NEED TO DEAL WITH
CHRONIC PAIN AND TRACK ACUTE
CARE UTILIZATION AND MAKE
DECISIONS ABOUT DISEASE
MODIFYING THERAPY AND DISCUSS
NOVEL THERAPIES AS WELL.
SO MOVING ON TO CEREBRAL
VASCULAR DISEASE.
THE STANDARDS EVERY PERSON
SHOULD UNDER GO AN EVALUATION
FOR DEFICITS DURING THE ANNUAL
COMPREHENSIVE VISIT.
EVERY ADULT SHOULD UNDER GO A
QUALITATIVE AND FUNCTIONAL
ASSESSMENT DURING THE ANNUAL
VISIT AND VALIDATED ASSESSMENTS
ARE NOT QUITE AVAILABLE BUT
HOPEFULLY PENDING AND WE'LL HAVE
A TOOL FOR THE SCREENING AND
RECOMMENDATION WAS TO REFER TO A
NEUROPSYCHOLOGIST IF
ABNORMALITIES IN NEUROLOGIC
FUNCTIONS ARE IDENTIFIED.
ONE OF THE THINGS I DIDN'T
MENTION IS WE DON'T GO AGAINST
EVIDENCE-BASED GUIDELINES AND
WE'RE NOT THROUGH THE SAME
RIGOROUS PROCESS USED FOR
GUIDELINES.
SO FOR CARDIOVASCULAR ASSESSMENT
CONSISTENT WITH ASH GUIDELINES
ADULTS WITH SICKLE CELL DISEASE
SHOULD BE SCREENED ANNUALLY AND
MAY REQUIRE ADDITIONAL TESTING
AND CAN YOU WALK FIVE BLOCKS ON
A FLAT SURFACE OR CLIMB THREE
FLIGHTS OF STAIRS OR EXPERIENCE
DIZZINESS WHEN YOU WALK AT NIGHT
UNABLE TO CATCH YOUR BREATH.
IF THE ANSWER TO ANY OF THESE IS
YES ECHO IS RECOMMENDED AND
DETERMINATION IS UNCLEAR AND IF
THE ANSWER TO ALL IS KNOWN
CLINICIAN CAN USE THEIR CLINICAL
JUNCTION AND REVIEW OF ALL
CLINICAL GUIDELINES TO APPROACH
CLINICAL DIAGNOSTIC TESTING.
AND HYPERTENSION.
AND IF AN ECHO IS PERFORMED
ATTENTION SHOULD BE PAID TO ALL
ASPECTS OF THE HEART AND ALL
ADULTS WITH SICKLE CELL DISEASE
SHOULD BE SCREENED FOR SYMPTOMS
OF OBSTRUCTIVE SLEEP APNEA AND
ROUTINE SCREENING WITH PFTs IS
NOT RECOMMENDED AS PER MULTIPLE
GUIDELINES BUT PROVIDERS SHOULD
HAVE A LOW THRESHOLD FOR
PERFORMING THESE WITH RISK
FACTORS AS PER THE ASH GUIDELINE
I'VE LISTED HERE BUT WILL NOT GO
OVER.
CAPACITY SHOULD BE PERFORMED AND
THE FOLLOWING SHOULD PROMPT A
REFERRAL TO PULMONARY.
WE OFTEN DO THE TESTS AND DON'T
KNOW WHEN OR REFER TO PULMONARY.
IF THEY CONNECTED TO AN LUNG
CAPACITY OF LESS THAN 70% AND
FCV IS LESS THAN 70% OR CONCERN
OF ASTHMA OR IF THEIR DIFFUSION
IS LESS THAN 60% PREDICT AND
INDIVIDUALS WITH INTERSTITIAL
LUNG DISEASE IDENTIFIED IN CT
IMAGING, THEY SHOULD BE REFERRED
TO PULMONARY MEDICINE PRIOR TO
TESTING AND THIS IS STANDARD OF
CARE IN PULMONARY MEDICINE.
AND SCREENED FOR CONSTIPATION IN
THE LARGE SPLEEN AND
THROMBOCYTOPENIA AND CONFIRMED
WITH ULTRASOUND IF THERE'S AN
ABSENCE OF SPLENNOMEGGALLY
PATIENTS MAY REQUIRE ADDITIONAL
WORKUP.
FOR RENAL THIS SHOULD NOT BE
SHOCKING THOSE WITH SICKLE CELL
DISEASE SHOULD HAVE A SCREENING
OF CREATIN AND WE DID NOT VOTE
ON WHEN TO INITIATIVE ARMS BUT
THAT WILL BE HAPPENING IN THE
FUTURE.
ALL PEOPLE WITH SICKLE CELL
DISEASE SHOULD BE SCREENED FOR
HISTORY OF PRIAPISM AND ERECTILE
DYSFUNCTION AND ACCESS TO
CONTRACEPTION IF DESIRED AND
THOSE WITH MENSTRUAL ASSOCIATED
VOC SHOULD BE CONSIDERED FOR
HORMONAL CONTRACEPTION AND
DISCUSS FERTILITY OPTIONS
INCLUDING THE RISK OF DISEASE
MODIFYING MODIFICATIONS AT EACH
VISIT AND REFERRALS TO REI IF
NEEDED.
SKIN, ALL PATIENTS SHOULD HAVE A
DETAILED SKIN EXAM FOR EVIDENCE
OF LEG ULCERS.
IF THERE'S RECURRENT SKIN
ULCERATIONS THERE SHOULD BE
CONSIDERATIONS OF DISEASE
MODIFYING THERAPY.
ALL ADULTS WITH SICKLE CELL
DISEASE SHOULD UNDER GO MEDICAL
HEALTH SCREENING FOR ANXIETY AND
DEPRESSION ON AN ANNUAL BASIS
USING TOOLS.
IRON ASSESSMENTS.
ALL PEOPLE WITH SICKLE CELL
DISEASE RECEIVING LONG TRANS
FUSION SHOULD HAVE MONITORING
FOR IRON OVERLOAD AND CHELATION
THERAPY AND REGULARLY MONITORED
FOR EFFECT.
MANY PATIENTS END UP GOING FROM
HOSPITAL TO HOSPITAL OFTEN
GETTING INAPPROPRIATELY
TRANSFUSED AND IMPORTANT TO
ASSESS FOR IRON OVERLOAD.
THE RECOMMENDATION INCLUDED ALL
PATIENTS WITH ON CHRONIC
TRANSFUSION SHOULD HAVE
MONITORING OF THEIR LIVER IRON
CONCENTRATION USING AN MRI.
BONE HEALTH.
ANNUAL VITAMIN W TESTING WITH
APPROPRIATE SUPPLEMENTATION AS
NEEDED.
RECOMMENDATION FOR AND THAT
SHOULD INCLUDE JOINT SYMPTOMS
AND IMAGING ONLY BASED ON
POSITIVE FINDINGS.
AND WHAT'S IMPORTANT IS THE
RECOMMENDATION THAT IT'S THE
SICKLE CELL CENTER THAT SHOULD
ENSURE AND IMPLEMENT AND TRACK
WHETHER OR NOT PATIENTS ARE
GETTING THE IMMUNIZATIONS
INCLUDING PNEUMOCOCCAL AND
INFLUENZA AND BOOSTING IS NEEDED
AND HEPATITIS C SCREENING FOR
THOSE ON THERAPY.
SO WHAT'S NEXT FOR THE
RECOMMENDATIONS AND HOW IS
STANDARDIZING THE ASSESSMENTS
HELPED?
HOPEFULLY BY STANDARDIZING THE
ASSESSMENTS THE SITES IN GRAN
DAD WILL BEGIN TO ENTER THE DATA
ON AN ANNUAL BASIS AND WE'LL BE
ABLE TO USE THE TOOLS TO ASSESS
HOW WE'RE MANAGING PATIENTS.
WE'VE ALREADY DONE THAT AND HAVE
HAD A COUPLE ABSTRACTS IN ASH
LOOKING HOW NOT WELL WE DO IN
THE REAL WORLD SETTING.
WE LOOKED AT HOW MUCH TIMES THE
PATIENTS HAVE BEEN SCREENED AND
ONLY THE 37% HAD ANNUAL
OBSERVATIONS.
MORE THAN A THIRD IN GRAN DAD
WITH FERRITIN WERE NOT ON IRON
CHELATION AND A QUARTER HAD
IMAGING STUDIES TO ASSESS.
AND WE HAVE NOT PUBLISHED WHAT
SITES DO BETTER THAN OTHERS.
IF THERE ARE SITES DOING WELL I
KNOW THERE'S AN OVERLOAD CLINIC
EMBEDDED IN A PROGRAM.
IF THE RESULTS ARE GREAT MAYBE
IT'S SOMETHING WE CAN LEARN FROM
AND SEE IF WE CAN'T IMPROVE SOME
OF THE NUMBERS.
A
WE HAVE A HEALTH MAINTENANCE
SHEET AND DATA FROM GRAN DAD AND
INCLUDED THE LABORATORY
SCREENING, WHETHER THE PATIENT
HAD THE ANNUAL EYE EXAM AND
WHETHER KIDS HAVE RECEIVED
RECOMMENDED VACCINATIONS AND
VERIFIES WHEN PATIENTS ARE NOT
ON DISEASE MODIFYING THERAPY.
AND I FIND IT HELPFUL BEFORE I
SEE PATIENTS AND THERE'S IMAGING
AND IMMUNIZATIONS AND NOTES
MOTIVATES ME TO HAVE THE TESTS
DONE.
FINALLY I WANT TO TALK ABOUT
PROs AND HOW WE MIGHT BE ABLE TO
USE THEM IN THE FUTURE.
THIS IS THE ASK ME DOMAINS.
THIS HAS BEEN FIELD TESTS IN
PEOPLE WITH SICKLE CELL DISEASE
AND SCORES HAVE BEEN
STANDARDIZED TO A MEAN OF 50 AND
ASQ ME SCORES ARE REQUIRED IN
GRAN DAD AND THEY'RE ASKED TO
COMPLETE IT ON THE ANNUAL BASIS.
WE LOOKED AT THE DATA A YEAR OR
TWO AGO WHERE WE LOOKED AT THE
RESULTS FOR PEOPLE PARTICIPATING
IN GRAN DAD AND FILLED OUT THE
ASQ ME AND I THINK THE SCORES
ARE INTERESTING AND WITH WHAT WE
CALL SEVERE DISEASE AND WHAT WE
DON'T AND I THINK PROs ARE
REALLY IMPORTANT TOOLS.
AND OUR COLLEAGUES WHO TAKE CARE
OF PEOPLE WITH RHEUMATOID
ARTHRITIS THINK THEY'RE
IMPORTANT TOOLS.
I'LL TALK HOW THEY'RE USED IN
RHEUMATOID ARTHRITIS AND BASIS
ON A REVIEW THAT IDENTIFIED
RANDOMIZED CONTROL TRIALS WHERE
PROs WERE ASSESSED AS A PRIMARY
OUTCOME OF THE STUDIES.
IT'S NOT DONE FOR SICKLE CELL
DISEASE.
44 OF THE TRIALS USE PROs
ASSESSED AT SECONDARY OUTCOMES.
THE MEASURES THEY USED SOME OF
WHICH ARE PROMISED TOOLS ARE
USED AND WIDELY AVAILABLE AND
PROVIDER IMPORTANT PERSPECTIVES
OFTEN NOT CAPTURED IN THE
RESPONSE CRITERIA.
SOUNDS FAMILIAR THEY USE FOR
RHEUMATOID ARTHRITIS.
DIVISION OF RHEUMATOLOGY AT
HOPKINS USED COMPUTERS FOR
PATIENTS TO COMPLETE THEM WHILE
WAITING IN THE WAITING ROOM AND
THEY REVIEW THE TOOLS AND SORT
OF DEVELOPED THIS IMAGE FOR EACH
PATIENT.
SO RED THEY'RE MORE THAN TWO
STANDARD DEVIATIONS AWAY FROM
THE STANDARD SCORE AND THIS IS
SOMETHING THEY CAN TRACK OVER
TIME TO ASSESS RESPONSE TO
THERAPY.
AND THEY USE THIS IN THE CLINIC
AND USE THIS TOOL TO CHANGE
PATIENT'S THERAPIES.
I THINK A LOT OF THIS COULD BE
POTENTIALLY SOMETHING WE CAN
TEST AND USE IN THE CLINIC
SETTING TO HELP IMPROVE OUTCOMES
FOR OUR PATIENTS.
I TALKED ABOUT ANNUAL SCREENING.
AND THE REAL KEY IS THE
IMPORTANCE WE STANDARDIZE CARE
ACROSS CENTERS AND TRY TO DO THE
SAME THINGS AND WE'LL DO QI ON
THE RESULTS AND OUTCOMES AND WE
ARE USING GRAN DAD FOR QUALITY
IMPROVEMENT AND REMIND PEOPLE
WHAT NEEDS TO BE DONE ON AN
ANNUAL BASIS.
THAT'S ALL I HAVE.
THANK YOU.
>> THANK YOU.
WE'LL TAKE QUESTIONS AT THE END
AND MOVE TO THE THIRD DISCUSSION
DR. GAURINO A MEDICINE AND
PEDIATRIC PHYSICIAN AND WORKING
CLOSELY WITH THE NATIONAL
ALLIANCE AMONG OTHER GROUPS IN
IMPROVE TRANSITION THROUGH
DOCUMENTATION AND THE
CONSENSUS-BASED RECOMMENDATION
AND LET STEPHANIE EXPLAIN MORE.
>> THANK YOU VERY MUCH.
WE'LL TALK ABOUT THE TRANSITION
OF CARE AND THIS CAN BE
CHALLENGING FOR PATIENTS WITH
SICKLE CELL DISEASE ON MANY
LEVEL AND WE'LL DEFINES
TRANSITION OF CARE AND TRANSFER
OF CARE IN SICKLE CELL DISEASE
AS VOTED UPON BY THE ALLIANCE.
THEN WE'LL DISCUSS WAYS WE CAN
START TO TRACK AND MONITOR THIS.
WE HEARD A COUPLE TIMES HOW
IMPORTANT THE ELECTRONIC HEALTH
RECORD FOR INCLUDING ACCURATE
COMPREHENSIVE INFORMATION FOR
PATIENTS WITH SICKLE CELL
DISEASE.
WE CAN EACH DO A GREAT JOB AT
OUR CENTER CREATING
INDIVIDUALIZED PAIN PLANS OR
CAPTURING SEVERITY BUT WHEN
PATIENTS TRANSITION INTO AN
ADULT COMPREHENSIVE PROGRAM SOME
INFORMATION GETS LOST.
HOW CAN WE HELP THE E.H.R. WORK
FOR US WHICH I KNOW IS SOMETIMES
A NOVEL CONCEPT.
HOW CAN WE USE E.H.R. TOOLS TO
CAPTURE AND SUPPORT TRANSITION.
I DON'T THINK I HAVE TO SPEND
TIME SHARING WITH THE AUDIENCE
HOW COMPLEX PROPOSITION
TRANSITIONING IS.
IT INVOLVES CLINICIANS, PATIENT
AND HEALTH SYSTEM AT MANY
LEVELS.
EVEN WITHIN THE PATIENT REALM
THERE ARE BIOLOGICAL,
PSYCHOLOGICAL AND SOCIOLOGICAL
FACTORS THAT CAN AFFECT
TRANSITION AND WHETHER IT GOES
WELL OR NOT WELL.
SO WE'RE ADDRESSING A COUPLE OF
THESE AREAS WITH THIS PROJECT.
SO I'M GOING TO TALK ABOUT TWO
PROJECTS IN PARALLEL.
THE FIRST THING WE STARTED
THINKING ABOUT WAS A PROBLEM
STATEMENT.
YOUNG ADULTS WITH SICKLE CELL
DISEASE WHO DO NOT SUCCESSFULLY
TRANSITION TO ADULT MEDICAL CARE
OR TO ANOTHER SICKLE CELL HOME
HAVING INCREASED UTILIZATION OR
RISK FOR SEVERE DEATH AND HOW
CAN WE FACILITATE THAT USING
E.H.R. SYSTEMS?
FIRST WE HAVE TO DEFINE WHAT
TRANSITION IS.
YOU KNOW IT CAN BE CHALLENGING.
ALSO IF WE'RE GOING TO USE THE
E.H.R. TO CAPTURE DATA IMPORTANT
FOR TRANSITION WHAT SORTS OF
THINGS DO WE WANT TO KNOW ABOUT?
WE STARTED OUT WITH A GROUP OF
SIX HEMATOLOGISTS, THREE OF WHOM
WERE PEDIATRIC, THREE OF WHOM
WERE PREDOMINANTLY ADULT AND
START TO COME UP WITH SOME OF
THE ELEMENTS THAT WOULD BE
IMPORTANT TO A TRANSITION
SUMMARY AND SENT THEM TO CENTERS
AND WENT THROUGH THE CONSENSUS
PROCESS AND AGGRAVATED THE DATA
AND DISCUSSED THE ELEMENTS WHICH
I'LL TALK ABOUT AND THEN CAME UP
ONE THE FINALIZED SET OF
IMPORTANT TRANSITION ELEMENTS.
I THINK IT REFLECTS SOME GOOD
FEEDBACK FROM PEDIATRIC AND
ADULT SICKLE CELL CLINICIANS AND
POTENTIALLY SOME OF THE ADULT
CLINICIANS WERE SURPRISED OR THE
PEDIATRIC CLINICIANS WERE
SURPRISED SOME OF THE DETAILS
THE ADULT CLINICIANS DIDN'T FEEL
WERE AS PERTINENT.
WHAT WE HAVE COME UP WITH TRIES
TO CAPTURE BOTH GROUPS NEEDS.
WE TOOK THE SETS OF ELEMENTS AND
I WORKED WITH TWO EHRs AND WE
PILOT THE TEMPLATES AND ARE
COLLECTING DATA ON FEASIBILITY
A
AND THINGS FOR WHICH WE HAVE THE
BEST EVIDENCE AND HOPE SOME MAY
SEEM LIKE COMMON SENSE BUT IT'S
IMPORTANT TO WRITE THEM DOWN AND
HAVE THEM AS OUR GO-TO
DOCUMENTS.
AND WE HAVE ADDITIONAL
RECOMMENDATIONS FOR WHICH WE
FEEL STRONGLY BUT THERE'S LESS
EVIDENCE.
SO REFERRING COMPREHENSIVE
PEDIATRIC AND CLINICIANS
PREFERABLY THE ENTIRE TEAM
SHOULD HAVE JOINT MEETINGS TO
DISCUSS PATIENTS NEAR TRANSITION
AND JOINT PEDIATRIC TO ADULT
TRANSITION SERVICE SHOULD BE
AVAILABLE.
THE PERCENTAGES ARE THE NUMBER
OF SICKLE CELL CENTERS THAT
AGREED WITH EACH OF THESE
STATEMENTS FOR REFERENCE.
AND EVERY COMPREHENSIVE SICKLE
CELL PROGRAM SHOULD HAVE A
UNIVERSAL CARE PLAN IN THE
E.H.R. TO TRACK SERVICES
RELEVANT WHICH IS SOMETHING
WE'LL TALK ABOUT LATER AND
PEDIATRIC SUMMARY E.H.R.
TRANSITION OF CARE HANDOFF NOTE
SHOULD BE UTILIZED TO FACILITATE
HANDOFF BETWEEN PEDIATRIC AND
ADULT CARE TRANSITION.
THESE ARE SOME OF THE WORK
YOU'LL SEE LATER IT CAN BE
UPDATED FOR THE TRANSITION OF
CARE.
THE GOAL IS NOT TO CREATE MORE
WORK BUT CREATE DOCUMENTS THAT
CAPTURE IMPORTANT INFORMATION
HELP CLINICIANS.
THERE'S A PROGRESS REPORT AFTER
THE INITIAL ADULT VISIT TO SEND
BACK TO THE REFERRING CLINICIAN
SO THE PEDIATRIC TEAM AND
PRIMARY CARE CLINICIAN KNOWS
WHAT HAPPENED.
THIS IS A STANDARD THAT ALL
COMPREHENSIVE PEDIATRIC AND
ADULT SICKLE CELL CENTERS SHOULD
TRACK TRANSITION OF CARE AND ALL
CENTERS SHOULD HAVE A TRANSITION
COORDINATOR OR PROGRAM DESIGNEE
TO FOLLOW PATIENTS FROM
PEDIATRIC TO ADULT CARE UNTIL
TRANSITION AND PROGRAMS HAVE
DIFFERENT WAYS OF DOING THIS OR
SUPPORTING PATIENTS AS THEY
TRANSITION SO IT WAS LEFT TO BE
ABLE TO ACCOMMODATE THE WAY
EVERYBODY DOES TRANSITION.
THE TIME GAP BETWEEN THE LAST
CLINICAL VISIT AND THE FIRST
CARE VISIT TO ESTABLISH CARE
SHOULD BE LESS THAN THREE MONTHS
AND TRYING TO MINIMIZE THE TIME
WHERE PATIENTS CAN GET LOST IN
FOLLOW-UP OR HAVE NEEDS NOT
BEING MET AND A FORMAL SYSTEM TO
IDENTIFY TRANSITIONING
ADOLESCENT OR PATIENTS NOT
HAVING AN INITIAL ADULT VISIT
WITHIN THE SIX MONTHS OF THE
LAST PEDIATRIC VISIT ESTABLISHED
AT BOTH CENTERS.
RELYING ON CENTERS TO BE SURE
THE PATIENTS GET TO WHERE THEY
NEED TO GO.
AND IT'S IMPORTANT TO REMEMBER
AS PATIENTS TRANSITION THEIR
INFORMATION ON THEIR TRANSFUSION
HISTORY SHOULD FOLLOW THEM.
SO THE INITIAL ADULT VISIT
SHOULD INCLUDE SOME
COMMUNICATION BETWEEN BLOOD
BANKS WITHOUT GENOTYPES OR
PHENOTYPING OR TRANSFUSION
HISTORY.
ONE OF THE MOST IMPORTANT THINGS
TO COME OUT OF THIS WORK IS
DEFINING TRANSITION OF WORK AND
TRANSFER OF CARE THE TWO
HALLMARKS OF THE PERIOD AND
DEFINE A TRANSFER OF CARE AS TWO
VISITS WITH THE SICKLE CELL
VISIT IN THE FIRST YEAR AND THEY
CAN BE IN PERSON OR TELEMEDICINE
TO ACCOMMODATE THE WAY HEALTH
CARE IS DELIVERED AND TO IMPROVE
UPTAKE AND MAYBE MORE RURAL
AREAS OR PLACES THAT DON'T HAVE
A SICKLE CELL CENTER WHERE
PATIENTS CAN PHYSICALLY GO.
INTEGRATION TO ADULT CARE WAS
DEFINED AS COMPLETION OF AT
LEAST 50% OF THE COMPREHENSIVE
VISITS IN THE FIVE YEAR PERIOD
AFTER TRANSFER OF CARE.
THIS MAY BE ONE OF THE MOST
IMPORTANT POINTS TO MAKE.
THE OTHER CRUCIAL PIECE IS THE
PATIENT IDENTIFIES THE CENTER AS
THEIR MEDICAL HOME HELPING THEM
FEEL THEY'RE INTEGRATED INTO THE
NEW CARE TEAM.
THE DEFINITIONS ALLOW US TO
TRACK SUCCESSFUL PROGRAMS OR
HELP US TRACK QUALITY OF
DIFFERENT INTERVENTIONS OR
METRICS OR UNDERSTAND HOW
PROGRAMS WORK OR WHERE THERE'S
OPPORTUNITIES FOR IMPROVEMENT
FOR TRANSITION OF CARE.
THESE ARE MOST THE ELEMENTS WE
DISCUSSED IN THE CONSENSUS
PROCESS.
THE ONES IN GREEN REACHED
CONSENSUS AND THE ONES IN RED
ARE NOT.
YOU CAN SEE IT INCLUDES A LOT OF
PERTINENT INFORMATION.
SOME OF WHAT THE ELEMENTS ARE
EASILY PUT INTO THE E.H.R. AS
DISCREET DATA ELEMENTS AND SOME
REQUIRE MORE FREE TEXT AND
NARRATIVE BOXES WHICH MAKES
THINGS HARDER IN TERMS OF DATA
COLLECTION OR POPULATING OR
CARRYING FORWARD.
AND LABS ON RECORD, VITAL SIGNS
AND HYDROXYUREA LABS AND DISEASE
MODIFYING THERAPY SECTION, GENE
THERAPY OR TRANSPLANT
INFORMATION FOR PATIENTS WHO HAD
UNDER GONE TRANSFORMATIVE
THERAPY.
THERE WAS SPECIFIC TRANSFUSION
ELEMENTS IMPORTANT TO CONVEY AND
A VARIETY OF COMPLICATIONS SOME
OF WHICH SHOWN HERE AND SPACES
FOR THE ACUTE PAIN PLAN AND
INPATIENT ADMISSIONS FOR
PATIENTS WITH NUANCED THINGS TO
CONVEY.
AND MEDICATIONS INCLUDED.
HOW DO YOU CAPTURE THE
INFORMATION IN THE E.H.R.?
THIS IS ONE OF MANY WAYS AND
MANY HAVE IMPLEMENTED SOLUTIONS
SIMILAR OR DIFFERENT IN YOUR
E.H.R.s BUT THE IDEA BEHIND THIS
PROJECT WITH THE NATIONAL
ALLIANCE IS TO COLLABORATE NOT
DUPE -- DUPLICATE AND CREATING
THE TOOLS IN ANY E.H.R. WE CAN
REFINE THEM AND DISTRIBUTE THEM
TO OUR CENTERS AND CREATE MORE
UNIFORMITY.
THERE'S ONE THE THINGS YOU CAN
USE TO CHART INFORMATION
CARRYING FORWARD THROUGH
DIFFERENT ENCOUNTERS AND THE
DIFFERENT TABS ON THE SIDE
REFLECT THE DIFFERENT SECTIONS
IN THE E.H.R. TRANSITION HANDOFF
ELEMENT.
THIS HAS INFORMATION ABOUT
RESEARCH PARTICIPATION REFERRING
CLINICIANS WHETHER OR NOT THEY
COMPLETED A TRANSITION
CURRICULUM THE DISEASE MODIFYING
THERAPIES AND SPECIFIC DOSES AND
DETAILS OF MEDICATIONS AS WELL
AS PAIN HISTORY.
AND MATRIX FOR THE SICKLE CELL
COMPLICATIONS AND MARK OFF THE
ONES PATIENTS EXPERIENCED WITH
DATES AND DETAILS.
THAT GOES IN THE FLOW SHEET TO
REVIEW DURING ANY ENCOUNTER.
THIS IS THE WAY OUR ED
CLINICIANS CAN ACCESS THE
PATIENT PAIN PLANS AND THAT'S
HOW WE STARTED TO DISSEMINATE
THAT INFORMATION.
YOU CAN ALSO TRACK SOME OF THESE
VALUES OVER TIME.
YOU CAN USE THIS TO POPULATE THE
CLINIC NOTE AND COMES UP AS A
SPECIFIC SICKLE CELL CLINIC NOTE
WHERE PRIOR MY NOTES WENT IN AS
PRIMARY CARE AND SEPARATES THEM
OUT AND ALLOWS CLINICIANS TO
LOOK AT THEM SPECIFICALLY FOR
THE SICKLE CELL PAIN PLAN.
THAT THE HOW WE ADDRESSED IT IN
SERNER.
AND IN EPIC WE CREATED A SMART
FORM FOR SICKLE CELL DISEASE.
ALL THE ELEMENTS HERE YOU SEE
ARE INDIVIDUAL DATA ELEMENTS IN
A SMART FORM.
EACH CLINICIAN UPDATES THE SMART
FORM AND USES IT TO POPULATE
THEIR NOTE.
THIS AVAILABLE IN EPIC AS A
WHOLE BASED ON THE MOST RECENT
UPDATE.
INSTITUTIONS HAVE TO OPT IN AND
UPLOAD THE SMART FORM BUT IT'S
THERE AND THERE MAY BE TWEAKING
SITES HAVE TO DO FOR THE DATA
ELEMENTS THAT MAY BE SLIGHTLY
DIFFERENT IN YOUR VERSION OF
EPIC.
SO THIS THEN USES THOSE SAME
TRANSITION ELEMENTS TO CREATE A
SENDING NOTE OR PEDIATRIC NOTE.
ONE THING WE'RE LOOKING TO WORK
OUT IS HOW TO DEAL WITH THE
PROTECTED HEALTH INFORMATION
ELEMENTS FOR MINORS OR
ADOLESCENTS RELATED TO OBSTETRIC
HISTORY OR SEXUALLY TRANSMITTED
DISEASE HISTORY OR OTHER ITEMS
OFTEN PROTECTED.
WE WANT TO BE COGNIZANT AND
STILL RELAY INFORMATION.
WHEN WE BUILT THE TEMPLATE WE
DIDN'T INCLUDE THEM TO AVOID
INFORMATION BEING INADVERTENTLY
RELAYED OR DISSEMINATED TO
PEOPLE TO WHOM IT SHOULD NOT GO.
THIS IS INFORMATION AVAILABLE
FOR PATIENTS.
THE CLINICAL TEAMS AT OUR
PEDIATRIC AND ADULT SICKLE CELL
CENTERS BEGAN USING THESE AND
WE'VE DONE REVISION BASED ON
CLINICIAN FEEDBACK AND
EXPERIENCING THINGS THAT WEREN'T
IN THERE OR NEEDED TO BE DONE
DIFFERENTLY.
WE ARE NOW GOING TO AND AFTER WE
TAKE THAT WE ARE ABLE TO
DISSEMINATE THE CODING THE FORMS
TO OTHER SITES TO CONTINUE TO
USE AND IMPROVE THEM AND THEN I
THINK LIKE MANY OF YOU KNOW THE
END STAGE GOAL IS TO CREATE A
NOTE OR SYSTEM WHERE THIS
INFORMATION CAN BE TRANSFERRED
ACROSS E.H.R.s SO THAT
REGARDLESS OF WHETHER A PATIENT
IS SEEN IN EPIC OR SERNER OR
ANOTHER E.H.R. PLATFORM YOU'RE
ABLE TO CONVEY THIS DATA SO IT'S
NOT LOST.
I HAVE TO THANK THE TEAMS AND
THOSE WHO CODED ALL THIS WORK
AND CELT WITH MYSELF AND ME IS
INFORMATICS CURIOUS BUT NOT VERY
SKILLED AND WERE HELPFUL AND THE
NATIONAL ALLIANCE FOR THE WORK
AND TRANSITION TEMPLATE TEAM.
THANK YOU SO MUCH FOR ALLOWING
ME TO SHARE THIS WITH YOU TODAY.
>> THANK YOU SO MUCH AND WE'RE
HAPPY TO TAKE ANY QUESTIONS.
ANY QUESTIONS ONLINE?
NO QUESTIONS IN PERSON?
I GUESS YOU'VE BEEN CLEAR.
>> THERE WAS A QUESTION ABOUT
VACCINES AND WHETHER IT NEEDED
TO BE TRACKED BY THE ADULT
SICKLE CELL PROGRAM.
THERE WAS LOTS OF DISCUSSION
ABOUT THE NEED FOR ONGOING
PNEUMOCOCCAL VACCINES IN OUR
POPULATION.
THE BASIC RECOMMENDATION IS TO
STICK WITH THE CDC GUIDELINE.
>> GREAT.
THANK YOU AGAIN FOR
ACCOMMODATING AND COMING IN
EARLY.
SO WE GIVE 20 MINUTES BACK TO
EVERYBODY FOR THE DAY AND THANK
YOU AGAIN FOR COMING TO THIS
WONDERFUL SICKLE CELL MEETING
FOR THE LAST THREE DAYS.
WE'VE TOUCHED FROM BONE MARROW
TRANSPLANT TO GENE THERAPY TO
SYSTEMS BIOLOGY AND ALL THE
NETWORKS AND ASH UPDATES AND CDC
UPDATES AND LOOK FORWARD TO HOUR
NEXT YEAR'S ANNUAL SICKLE CELL
MEETING.
UNTIL THEN, GOOD-BYE.