>> GOOD MORNING AND WELCOME BACK
TO THE FIFTH ANNUAL NIH HEAL
INITIATIVE SCIENTIFIC MEETING.
I'M HAIRK TI'LL BE YOUR EMCEE AE
TAMARA FROM THE NATIONAL
INSTITUTE ON DRUG ABUSE.
FOR THOSE WHO COULD NOT JOIN US
YESTERDAY MORNING, WE ARE
EXCITED TO HAVE ATTENDEES
SPANNING THE FULL HEAL
COMMUNITY, INCLUDING
PRE-CLINICAL BASIC RESEARCHERS
TO IMPLEMENTATION SCIENCE
RESEARCHERS, ALL WORKING TO
ADDRESS THE OPIOID USE DISORDER
AND CHRONIC PAIN CRISES.
WE ARE ALSO JOINED BY NIH
LEADERSHIP AND STAFF, AS WELL AS
COMMUNITY PARTNERS, ADVISING
HEAL PROJECTS, AND THE HEAL
INITIATIVE AS A WHOLE.
MANY WITH LIVED AND LIVING
EXPERIENCE.
WE ARE HONORED TO HAVE SO MANY
CRITICAL PERSPECTIVES AT THIS
MEETING AND AN EAGERNESS TO COME
TOGETHER.
THIS IS A HYBRID MEETING.
MOST SESSIONS WILL BE
LIVESTREAMED TO VIRTUAL
ATTENDEES VIA THE VIRTUAL EVENT
PLATFORM.
BOTH VIRTUAL AND IN-PERSON
ATTENDEES HAVE ACCESS TO THIS
PLATFORM.
YOU RECEIVED THE ACCESS LINK VIA
EMAIL EARLIER THIS WEEK.
THE PLATFORM INCLUDES ADDITIONAL
RESOURCES INCLUDING ALL RESEARCH
POSTERS AND THEIR ABSTRACTS.
ALL MEETING SESSIONS ARE BEING
RECORDED, AND WILL BE AVAILABLE
ON THE PLATFORM FOLLOWING THE
MEETING.
THE PLENARY SESSIONS IN THIS
ROOM WILL ALSO BE LIVESTREAMED
TO THE PUBLIC VIA NIH VIDEOCAST.
RECORDINGS WILL BE AVAILABLE ON
THE HEAL WEBSITE.
IN ADDITION TO ATTENDING
SESSIONS, WE ENCOURAGE YOU TO
PARTICIPATE DURING Q & A AND
SUGGEDISCUSSION SESSIONS.
FEEL FREE TO STEP UP TO A
MICROPHONE AND THE MODERATOR
WILL CALL ON YOU.
THERE WILL ALSO BE MICROPHONES
IN THE BREAKOUT ROOMS.
PLEASE ALWAYS USE THEM TO ENSURE
YOU CAN BE HEARD.
VIRTUAL PARTICIPANTS, PLEASE USE
THE CHAT FUNCTION TO ASK YOUR
QUESTIONS.
WHILE THERE ARE NO FORMAL POSTER
SESSIONS TODAY, ALL OF THE
RESEARCH POSTERS WILL REMAIN IN
SALONS E THROUGH H UNTIL THE END
OF THE MEETING.
FEEL FREE TO GO IN AND VIEW THE
POSTERS AS YOU HAVE TIME.
ALSO BE SURE TO CHECK OUT THE
VIRTUAL ATTENDEE POSTER ON THE
VIRTUAL MEETING PLATFORM.
THERE ARE SEVERAL PROGRAM BOOST
BOOTHS SET UP IN THE FOYER
OUTSIDE THIS ROOM.
BE SURE TO VISIT THE HEAL DATA
ECOSYSTEM BOOTH, WHERE THEY CAN
ASSIST YOU IN COMPLETING KEY
STEPS FOR MAKING YOUR DATA
HEAL-COMPLIANT AND PREPARING
DATA FOR PUBLICATION AND
DISSEMINATION.
COMPLEATING STUDY REGISTRATION
AND THE CDER STUDY LEVEL
METADATA FORM WILL AUTOMATICALLY
ENTER YOU INTO THE RAFFLE FOR A
CHANCE TO WIN EXCITING PRIZES.
HEAL CONNECTIONS ALSO HAS A
BOOTH WHERE YOU CAN LEARN MORE
ABOUT HOW THEY ARE CREATING
PATHWAYS TO BUILD AND SUSTAIN
COMMUNITY PARTNERSHIPS AND
SUPPORTING RESEARCHERS IN
MEANINGFULLY SHARING RESULTS
WITH THOSE THAT WILL BENEFIT
MOST FROM THE RESEARCH FINDINGS.
WE WILL ALSO HEAR FROM HEAL
CONNECTIONS ABOUT THE COMMUNITY
ENGAGEMENT WORK THEY ARE DOING
LATER THIS AFTERNOON.
THE PURPOSE NETWORK IS ALSO
AVAILABLE TO DISCUSS HOW THEY
ARE CONNECTING PAIN RESEARCHERS
ACROSS THE CONTINUUM OF PAIN
RESEARCH FROM ALL DISCIPLINES
AND CAREER STAGES.
AS ALWAYS, IF YOU HAVE
QUESTIONS, PLEASE VISIT THE
REGISTRATION AND INFORMATION
DESK IN THE FOYER.
SO TO KICK OFF OUR SECOND DAY,
WE HAVE A SESSION TITLED
"ENGINEERING TREATMENTS FOR PAIN
AND OPIOID USE DISORDER."
DR. ALL ALI REZAI FROM WEST VIRA
UNIVERSITY AND DR. PRASAD
SHIRVALKAR FROM UNIVERSITY OF
CALIFORNIA SAN FRANCISCO WITH
EDWARD MOWERY WILL SHARE.
DR. AKLIN OF THE NATIONAL
INSTITUTE ON DRUG ABUSE WILL
MODERATE THE SESSION.
SO PLEASE JOIN ME IN WELCOMING
DRS. AKLIN, REZAI, SHIRVALKAR
AND MR. MOWERY.
>> THANK YOU VERY MUCH, AND
WELCOME.
I'M EXCITED TO INTRODUCE MY
PANEL TODAY.
VERY EXCITING ON ENGINEERING
TREATMENTS FOR PAIN AND OPIOID
USE DISORDER.
DR. PRASAD SHIRVALKAR IS
ASSOCIATE PROFESSOR OF
ANESTHESIOLOGY, NEUROLOGY AND
NEUROLOGICAL SURGERY AT UCSF.
HIS FOCUS AS A NEUROLOGIST AND
PAIN MEDICINE SPECIALIST IS TO
TREAT THE WHOLE SPECTRUM OF
CHRONIC PAIN SYNDROMES.
PRASAD'S LAB RECENTLY DISCOVERED
THE FIRST DIRECT BRAIN
BIOMARKERS TO TRACK PAIN
SEVERITY, AND A LOT OF THIS WORK
NOW IS BEING USED TO DEVELOP
NEUROMODULATION TECHNIQUES TO
TREAT PAIN.
MR. ED MOWERY, TO HIS IMMEDIATE
RIGHT, IS A CLINICAL TRIAL
PARTICIPANT.
ED IS A COMMUNITY PARTNER ON
PRASAD'S STUDY.
ED IS A MUSICIAN FROM
ALBUQUERQUE NEW MEXICO, AND
PREVIOUSLY SUFFERED FROM CHRONIC
PAIN OVER 18 YEARS.
ED HAS UNDERGONE OVER 32 SPINAL
SURGERIES WITHOUT MEANINGFUL
BENEFIT.
HE ALSO HAD SHARP, STABBING PAIN
IN HIS LEGS AND FEET FROM
COMPLEX REGIONAL PAIN SYNDROMES
THAT PREVENTED HIM FROM WORKING
OR PLAYING MUSIC.
SINCE ENROLLING IN PRASAD'S
STUDY AT UCSF, HE IS NEARLY
PAIN-FREE AND HAS STARTED
WORKING FULL TIME AND PLAYING
MUSIC AGAIN.
LAST BUT NOT LEAST, DR. ALI
REZAI IS ASSOCIATE DEAN OF
NEUROSCIENCE AT WEST VIRGINIA
UNIVERSITY AND EXECUTIVE CHAIR
AND DIRECTOR AT WEST VIRGINIA
UNIVERSITY ROCKEFELLER
NEUROSCIENCE INSTITUTE.
DRHE IS AN EXPERT IN
NEUROMODULATION FOR MOVEMENT
DISORDERS, CHRONIC PAIN, AND
OTHER NEUROBEHAVIORAL DISORDERS.
WITH RESEARCH SPANNING
PARKINSON'S DISEASE, CHRONIC
PAIN, ADDICTION, AND
ALZHEIMER'S.
HE HAS OVER 200 SCIENTIFIC
PUBLICATIONS WITH AN H INDEX OF
92, AND THE CURRENT P.I. ON A
NIDA-FUNDED UG3 UH3 GRANT TO
FOCUS ON DEEP BRAIN STIMULATION
AND FOCUS ULTRASOUND FOR OPIOID
USE DISORDER.
DR. REZAI IS PAST PRESIDENT OF
THE CONGRESS OF NEUROLOGICAL
SURGEONS AND NORTH AMERICAN
NEUROMODULATORY SOCIETY.
THANK YOU VERY MUCH, GENTLEMEN,
AND LOOKING FORWARD TO A
FRUITFUL PRESENTATION.
THANK YOU.
>> THANKS SO MUCH, WILL, AND
THANKS, DR. VOLKOW,
DR. KOROSHETZ AND ALL OF US FOR
BEING HERE.
THANKS ESPECIALLY, ED, FOR
MAKING IT ALL THE WAY HERE FROM
ALBUQUERQUE.
I'M A NEUROLOGIST AND PAIN
PHYSICIAN AND GOING TO TALK TO
YOU TODAY ABOUT OUR EFFORTS TO
DEVELOP A NEW TREATMENT, AS WELL
AS UNDERSTAND MECHANISMS IN THE
BRAIN FOR CHRONIC PAIN.
IT'S BEEN KNOWN FOR SOME TIME
THAT CHRONIC PAIN IS VERY
PREVALENT.
IN A NEW STUDY, IT ACTUALLY
DEMONSTRATES THAT INCIDENCE IS
HIGHER THAN DEPRESSION OR
DIABETES IN A SINGLE-YEAR STUDY.
THE URGENCY OF CHRONIC PAIN WAS
COMMUNICATED OR AN ATTEMPT WAS
MADE TO COMMUNICATE IT IN THE
90s BY CALLING CHRONIC PAIN AS
THE FIFTH VITAL SIGN.
BUT AS OPPOSED TO THE OTHER FOUR
VITAL SIGNS, THERE'S NO
OBJECTIVE MEASURE OF PAIN.
WHEN I TALKED TO A MENTOR OF
MINE AND TOLD HIM, HOW CAN WE
ONTIVELY MEASURE PAIN, HE ASKED
ME, OH, YOU MEAN A K3 INDICATOR?
>> I'VE NEVER SEEN ANYTHING LIKE
IT EITHER, RIGHT?
ONE THING THEY GOT RIGHT WAS
THAT I THINK THE K3 INDICATOR,
IF ONE EXISTS, IS PROBABLY GOING
TO COME FROM THE BRAIN.
SO THAT WAS PRETTY PRESCIENT.
I'M GOING TO TALK TO YOU TODAY
ABOUT OUR ATTEMPTS TO DECODE
PAIN FROM THE BRAIN OR
UNDERSTAND OBJECTIVE CORRELATES
OF SUBJECTIVE PAIN PERCEPTION,
AND THEN TALK ABOUT THE CLINICAL
TRIAL THAT ED IS IN, AND HE'LL
COME AFTERWARDS AND SHARE SOME
OF HIS EXPERIENCE.
WE'VE KNOWN FOR MANY DECADES
THAT THERE ARE SIGNALS OF PAIN
IN THE BRAIN THAT TRACK
SUBJECTIVE EXPERIENCE.
MOST OF HISTORICAL RESEARCH, I
WOULD ARGUE, HAS BEEN DONE IN
HEALTHY PEOPLE, USING
EXPERIMENTAL PAIN.
NONETHELESS, WE'VE LEARNED A LOT
ABOUT KEY BRAIN REGIONS OR
CIRCUITS THAT ARE IMPORTANT
USING MAYBE A HEAT PROBE ON A
PATIENT'S HAND.
MOST NOTABLY, RECENTLY THE WORK
FROM WAGER'S NEUROLOGIC PAIN
SIGNATURE WAS PRECEDED BY WORK
BY ROBERT COGHILL AND CATHY
BUSHNELL'S GROUP ALSO USING FMRI
AND PET WHICH HAD SOME
CONCORDANCE IN TERMS OF AREAS
THAT WERE IMPORTANT FOR PAIN,
SUCH AS ANTERIOR SINK LAT
CORTEX, AREAS LIKE THE INSULA,
MEDIAL PREFRONTAL CORTEX.
HOWEVER, I WILL SAY SOME OF THE
MOST IMPORTANT WORK IN ACTUALLY
LOOKING AT REAL WORLD CHRONIC
PAIN IN WORK DONE IN CHICAGO
WHERE THEY LOOK AT PATIENTS WHO
HAVE ACUTE OR SHORT TERM LOW
BACK PAIN, WHAT BRAIN REGIONS OR
WHAT ACTIVITY ACROSS THE BRAIN
MIGHT DISTINGUISH THOSE PATIENTS
WHO RECOVER FROM THOSE PATIENTS
WHO PERSIST TO HAVE DEBILITATING
CHRONIC PAIN.
USING TIME POINT OF FOUR MRIs
OVER ONE YEAR, THERE'S CERTAIN
AREAS THAT SHOW DEGENERATION OR
DECREASE IN GREY MATTER VOLUME
AND THERE'S OTHER AREAS THAT IN
THE PREFRONTAL CORTEX THAT
APPEAR TO HAVE FUNCTIONAL
CHANGES BUT I THINK THE QUESTION
STILL REMAINS, WHAT SIGNALS
MIGHT TRACK THE SPONTANEOUS
NATURE OF FLUCTUATING CHRONIC
PAIN OVER DAYS, HOURS, ET CET
CETERA.
SO WE TEND TO TALK ABOUT CHRONIC
PAIN OR CONCEPTUALIZE IT IN
THREE DIMENSIONS AS THE
SOMATOSENSORY, THE PHYSICAL, HOW
SEVERE IS IT, WHERE IS IT, THE
EMOTIONAL OR MOTIVATIONAL, AS
WELL AS THE EFFECT THAT IT HAS
ON ATTENTION AND MEMORY.
THAT'S THE COGNITIVE.
IN A REDUCTIONIST WAY, WE CAN
MAP THESE DIFFERENT DIMENSIONS
ON TO DIFFERENT BRAIN CIRCUITS,
BUT I THINK IT'S CLEAR THAT NO
BRAIN REGION DOES ANYTHING,
RIGHT?
IT'S IN CONCERT WITH OTHER BRAIN
REGIONS THAT THERE'S A NETWORK
FLOW OF INFORMATION THAT LEADS
TO BEHAVIOR AND LIKELY
SUBJECTIVE PERSONAL EXPERIENCE.
AND SO NONETHELESS, I THINK IT'S
IMPORTANT TO AT LEAST TRY TO
IDENTIFY WHAT ARE CIRCUITS THAT
MIGHT BE MORE IMPORTANT FOR
CERTAIN EXPERIENCES THAN OTHERS.
THIS MIGHT HELP US TO TRACK AND
MORE IMPORTANTLY TREAT CHRONIC
PAIN.
SO WE USE THE APPROACH OF DEEP
BRAIN STIMULATION AS AN ATTEMPT
TO ENGINEER A TREATMENT FOR
CHRONIC PAIN.
DBS HAS BEEN ESTABLISHED AS A
TOOL FOR MANY DISORDERS WHERE
CERTAIN TARGETS, SINGLE TARGETS
IN THE BRAIN HAVE BEEN SHOWN TO
WORK ACROSS PATIENTS WITH
SURPRISING EFFICACY.
BUT THERE'S STILL NO BEST SINGLE
TARGET FOR PAIN.
THERE'S NO BRAIN REGION OR PAIN
CENTER IN THE BRAIN, RIGHT?
IT SEEMS TO BE MORE OF A
DISTRIBUTED NETWORK THAN MANY
OTHER DISEASES WHICH IS MORE
CHALLENGING TO FIND SOMETHING
THAT GENERALIZES.
SO ACROSS THE YEARS, STARTING IN
1960 AND THEN IN THE 70s AT
UCSF ACTUALLY, FOLKS HAVE TRIED
TO USE DBS AT VARIOUS TARGETS TO
TREAT CHRONIC PAIN.
THERE WAS A BIG INDUSTRY TRIAL
IN THE 1990s THAT THEN KIND OF
INSPIRED YET ANOTHER TRIAL USING
THE ANTERIOR CINGULATE DBS, BUT
THE MAIN MESSAGE HAS BEEN,
ANYTHING THAT WORKS IN THE SHORT
TERM SEEMS TO FADE.
AND MOREOVER, EVEN THE SINGLE
DOUBLE BLINDED RANDOMIZED TRIAL
HAD A NEGATIVE OUTCOME.
SO THE MAIN PROBLEMS ARE, YOU
KNOW, MOST PATIENTS ARE FAILED
BY ALL THERAPIES.
THE EFFECTIVE TARGETS ARE
UNKNOWN, AND IT WEARS OFF AFTER
TIME.
SO WE ASKED CAN WE BUILD CLOSED
DBS SOLUTIONS, SPECIFICALLY, CAN
WE TRY TO ENGINEER A SYSTEM THAT
LOOKS LIKE A THERMOSTAT?
JUST LIKE A THERMOSTAT MIGHT
TURN ON AND OFF IN RESPONSE TO
THE MEASUREMENTS OF AMBIENT
HEAT, CAN WE MEASURE CHRONIC
PAIN?
THAT'S KIND OF THE FIRST STEP.
SO WE PUBLISHED A STUDY RECENTLY
IN FOUR PATIENTS, THREE OF WHOM
HAD POST STROKE PAIN AND ONE HAD
PHANTOM LIMB PAIN.
THESE PATIENTS WERE IMPLANTED
WITH A NOVEL DEVICE THAT ALLOWED
US TO STIMULATE BUT ALSO RECORD
ACTIVITY FROM BRAIN REGIONS.
WE RECORDED FROM ELECTRODES
IMPLANTED IN THE ANTERIOR
CINGULATE CORTEX AS WELL AS TH
THE -- FRONTAL CORTEX WHILE
PATIENTS REPORTED THEIR PAIN
MULTIPLE TIMES A DAY OVER MANY
MONTHS.
HERE IS AN EXAMPLE PATIENT OVER
FOUR MONTHS AND EACH BLACK DOT
REFLECTS A PAIN REPORT THEY GAVE
US, BUT ALSO THEY WOULD HIT A
BUTTON ON THE REMOTE AND WE
WOULD GET A BRAIN READING OR A
SNAPSHOT OF BRAIN ACTIVITY.
SO USING THIS BRAIN ACTIVITY,
ESSENTIALLY USED A TRANSFORM
WHERE WE DECOMPOSED THE NEURAL
SIGNALS INTO CONSTITUENT
WAVELENGTHS KIND OF LIKE AN
EQUALIZER WOULD DO FOR MUSIC.
SO BY TAKING THE FREQUENCY
CHARACTERISTICS OF THESE BRAIN
SIGNAL, WE ASKED CAN WE PREDICT
AT LEAST WHEN PATIENTS ARE GOING
TO BE IN HIGH VERSUS LOW PAIN.
USING ACTIVITY FROM EITHER THE
ANTERIOR CINGULATE OR THE
ORBITOFRONTAL CORTEX WE COULD
PREDICT IN ALL PATIENTS, AND I
THINK THIS WAS VERY SURPRISING
BUT REASSURING TO US, THAT IT IS
IT IS FEASIBLE TO TRACK
SUBJECTIVE HIGH VERSUS LOW
STATES IN THE BRAIN.
HERE'S A MAP OF EACH PATIENT'S
NEURAL SIGNATURE THAT WE USED TO
DECODE THEIR PAIN.
AND SPECIFICALLY WHAT I THOUGHT
WAS INTERESTING IS THAT THERE'S
A LOT OF INTRAINDIVIDUAL
VARIABILITY.
THIS IS REAL WORLD CHRONIC PAIN.
WHEN WE LOOKED AT EXPERIMENTAL
PAIN, WE FOUND SIGNATURES IN TWO
PATIENTS WHERE WE COULD
SUCCESSFULLY DECODE ACUTE PAIN,
IT DID NOT GENERALIZE.
SO THIS IS AN IMPORTANT PROOF OF
PRINCIPLE, I THINK, THAT DIRECT
BRAIN SIGNALS CAN ACTUALLY TRACK
CLINICAL CHRONIC PAIN STATE, THE
BIOMARKERS APPEAR TO BE
DISTINCT, REINFORCING OUR
INTUITION CLINICALLY, BUT AN
IMPORTANT NOTE, YOU KNOW, THAT
BIOMARKERS OF PAIN SHOULD NOT BE
USED TO UNDERMINE OR -- I THINK
THEY CAN ADD VALIDATION FOR PAIN
WHEN MRIs ARE NEGATIVE, BLOOD
TESTS ARE NEGATIVE.
IT MIGHT BE ACTUALLY AN
OPPORTUNITY TO HELP DIAGNOSE OR
MONITOR DISEASE.
BUT I THINK DAVIS SAID IT BEST,
THAT PAIN IS DEFINED BY AN
INDIVIDUAL AS THEIR TBROWND
TRUTH.
GROUND
TRUTH.
SO WE APPLY THEM IN A CLINICAL
TRIAL TO TRY TO IDENTIFY WHAT IS
THE BEST REGION NOW TO
STIMULATE, TO ACTUALLY ACHIEVE
PAIN RELIEF.
SO HERE, WHAT WE DID, IF YOU
LOOK ON THE BOTTOM LEFT, FOR 10
DAYS, WE USED AN APPROACH USING
STEREO EEGs WHERE WE IMPLANT
PATIENTS' BRAIN TARGETING
SPECIFIC BRAIN REGIONS THAT WE
BELIEVE ARE IMPORTANT IN PAIN,
AND WE SYSTEMATICALLY STIMULATE
OVER 10 DAYS TO IDENTIFY THE
BEST TARGET FOR PAIN RELIEF.
ONCE WE ACTUALLY ACHIEVE, MAYBE,
A HINT OF RELIEF, WE PERFORM
DOUBLE BLINDED SHAM CONTROLLED
TESTING IN THE HOSPITAL.
SO MY TEAM IS IN THE ROOM FOR
EIGHT HOURS A DAY, FOR 10 DAYS,
WE GOT TO KNOW ED REAL WELL
DURING THIS TIME.
AND SO IF THE PATIENTS GET 50%
RELIEF OR MORE, WHAT WE DO IS WE
IMPLANT A PERMANENT BRAIN
IMPLANT AND WE FOLLOW THEM FOR
TWO YEARS.
WE IMPLANT THE PERMANENT DEVICE
CONNECTING ELECTRODES THAT
TARGET THE BEST SITE THAT WE
OBTAINED IN THE DISCOVERY TRIAL
PERIOD.
SO WE THEN USED AGAIN A
PERSONALIZED APPROACH TO DERIVE
BIOMARKERS AND TRY TO IMPLEMENT
A SIMPLE SCHEME, THE SIMPLEST
THING IS CAN WE TURN THE DEVICE
ON AND OFF IN RESPONSE TO
ONGOING BIOMARKERS.
TO DATE, WE'VE HAD SEVEN
PATIENTS ENROLLED.
SIX PATIENTS HAVE UNDER DTS GONE
THE EXPLORATORY TRIAL PERIOD.
OF THOSE SIX, FIVE OF THEM HAVE
PROCEEDED TO A PERMANENT BRAIN
IMPLANT.
SO FIVE OUT OF SIX PATIENTS SO
FAR HAVE HAD CLINICALLY
MEANINGFUL RELIEF.
I WANT TO TALK VERY BRIEFLY
ABOUT ED MOWERY HERE.
AND THEN, YOU KNOW, LET YOU HEAR
FROM HIM DIRECTLY.
SO ED WAS RCS05.
THAT'S HOW WE WOULD REFER TO
HIM, PHI SAFE MANNER.
HE WAS 51 YEARS OLD WHEN HE MET
US, THAT WAS BACK IN 2021.
HEAVY METAL MUSICIAN FROM
NEW MEXICO.
HE HAD CHRONIC PAIN SINCE THE
AGE OF 15.
HE TOLD ME HAD A KNEE SURGERY
WHEN HE WAS 15, AND AT THIS
TIME, I MEAN, YOU CAN ONLY
IMAGINE, HE'S BEEN LIVING WITH
PAIN FOR THIS WHOLE TIME, BUT
HE'S HAD OVER 32 SURGERY,
INCLUDING IN HIS NECK, LOW BACK,
JOINTS.
HIS PAIN IS ALL OVER THE LIMBS,
BUT HE WAS DIAGNOSED WITH CRPS,
COMPLEX REGIONAL PAIN SYNDROME,
WHICH IS PARTICULARLY HARD TO
TREAT SYNDROME.
IT INTERFERED WITH HIS LIFE
OBVIOUSLY.
BUT NOTABLY, LIKE MANY PATIENTS,
HE'S TRIED OVER 20 MEDICATIONS,
STEROID INJECTIONS, SPINAL CORD
STSTIMULATOR, PHYSICAL THERAPY D
STILL WAS DISABLED.
HERE ARE SOME PISHTS THAT I
THINK MANY PEOPLE ARE FAMILIAR
WITH BUT CLEARLY YOU'VE BEEN
THROUGH A LOT, ED, RIGHT?
SO WHEN WE MET ED IN JUNE 2021,
THIS WAS THE PICTURE THAT HE
DREW US.
HIS BRAIN, YOU COULD SEE RIGHT
HERE, I'M GOING TO SHOW YOU,
IT'S FINISHING UP IN THE LAST
MINUTE, AND AS WE PEEL AWAY, YOU
CAN SEE THE ELECTRODES THAT WERE
IN HIS BRAIN.
AND IN THE HOSPITAL, HE
UNDERWENT TESTING AND YOU COULD
SEE THE PAIN MAPS HE STARTED
DRAWING, HE COULD SEE PAIN
APPEARS TO EVEN REALLY HAVE
MELTED OFF HIS BODY, WHICH WE
WERE AMAZED, RIGHT?
SO JUST TO SHOW YOU WHAT THAT
LOOKED LIKE DIRECTLY FROM ED'S
MOUTH, THIS WAS IN THE HOSPITAL
WHEN WE WERE TESTING.
>> SO, OF COURSE, YOU KNOW, I'M
BIASED BECAUSE HE'S IN THE ROOM
BUT HE GOT A PERMANENT IMPLANT
EVENTUALLY.
WE WENT ON TO DO TESTING FOR THE
LAST TWO YEARS AND ESSENTIALLY
HERE YOU CAN SEE HIS CLOSED LOOP
PERFORMANCE ON THE Y AXIS, PAIN
SEVERITY SCORES.
HIS OPEN LOOP STIMULATION, YOU
KNOW, HE WAS HITTING ZEROs
VERY OFTEN.
CLOSED LOOP, WE'RE CONTINUING
THE ANALYSIS NOW BUT IT LOOKS
LIKE HE HAS LESS PAIN SPIKES IN
COMPARISON TO SHAM AND BASELINE.
LAST BUT NOT LEAST, I WANTED TO
SHOW A VIDEO BUT IN THE INTEREST
OF TIME I'M GOING TO PASS IT ON
TO YOU, ED, AND JUST SAY THANKS
AGAIN FOR ED FOR BEING HERE, AND
OUR WHOLE TEAM.
THERE WE GO.
FOR BEING ABLE TO, YOU KNOW --
BEING ABLE TO LEARN A LOT ABOUT
THE BRAIN AND HELP FOLKS LIKE
YOU.
>> HI, EVERYBODY.
I'M EDWARD MOWERY.
I AM THE FOUNDER, VOCALIST AND
BASSIST OF METAL BAND TWINAKU.
OUR LABEL -- FROM MILAN, ITALY.
THE SAME ALBUM RECORDED DURING
THE MEDICAL TRIAL IS ABOUT TO BE
RELEASED ON VINYL AND DC.
I AM ALSO AN AUDIO RECORDING AND
ELECTRONIC AND COMPUTER ENGINEER
BEFORE I WENT TO SCHOOL, I
WORKED IN RESTAURANTS, I STARTED
AS A DISHWASHER AND BECAME A
CHEF AND THEN DECIDED IT WAS
TIME TO GO TO SCHOOL.
I GREW UP AND GRADUATED IN
NEW MEXICO.
I'M SURE YOU HAVE ALL SEEN
OPPENHEIMER RIGHT NOW AND ARE
FAMILIAR WITH OPPY'S TOWN.
MOM WAS PART OWNER OF REALTY AND
MY FATHER WAS IN THE ARMY AND
NUCLEAR ENGINEER.
I'M MARRIED TO MY BEAUTIFUL WIFE
STEPHANIE AND WE LIVE IN
ALBUQUERQUE, NEW MEXICO.
WE ARE REUNITED HIGH SCHOOL
SWEET HEARTS MARRIED IN 2012
AFTER 22 YEARS APART.
SHE'S THE ONLY ONE THAT TRULY
KNOWS WHAT I'VE BEEN THROUGH.
SHE'S LIVED IT WITH ME.
SO SHE HAS ALSO BEEN THROUGH IT.
IMAGINE THE PERSON YOU LOVE
SCREAMING IN THE MIDDLE OF THE
NIGHT IN PAIN, NIGHT AFTER
NIGHT, NOT KNOWING WHEN IT'S
EVER GOING TO END.
MY DAD ALSO HAS STOOD IN FRONT
OF CONGRESS DURING ANOTHER
CRISIS YEARS AND YEARS AGO AND
TOMORROW I'LL BE STANDING IN
FRONT OF CONGRESS FOR A WHOLE
NEW CRISIS, THE OPIOID CRISIS.
I DRIVE FOR A RIDESHARING
COMPANY PART-TIME AND I SEE THE
RESULTS OF THE CRISIS EVERY TIME
I WORK.
OPIATES HAVE THEIR PLACE BUT
THEY DON'T BELONG ON THE
STREETS.
IN MY FINAL DECISION TO GO
THROUGH WITH THE TRIAL, WITH
PRASAD'S KEEM AND UCSF, WHAT I
WANTED MOST WAS, OF COURSE, TO
BE OUT OF PAIN.
BUT I ALSO WANTED TO GET OFF THE
MEDICATIONS.
AND AT ONE TIME, I WILL START
WEANING WITHIN THE NEXT COUPLE
MONTHS, I START WEANING OFF
MORPHINE, LYRICA AND CYMBALTA.
MY PAIN SPECIALIST IS READY.
THAT'S VERY RARE WHEN ANYONE ON
HIS PRACTICE ARE TRYING TO WEAN
OFF THE DRUGS, AND THEY'RE
EXCITED TO HELP ME GET GOING
WITH ALL OF THAT.
DR. NARIN WAS THE ONE WHO
DIAGNOSED ME WITH CRPS IN 2017.
I USED TO BE A PRETTY HARD CORE
DOWNHILL SKIER AND A SOCCER
GOALIE.
AFTER MY FIRST KNEE INJURY ON
THE SOCCER FIELD REQUIRING
SURGERY THE A 14 YEARS OLD, I
FOUND THE GUITAR AND WAS
INSTANTLY HOOKED.
SINCE 14 YEARS OLD, I'VE HAD 29
SURGERIES, BOTH FEET, BOTH
KNEES, I'VE HAD MY KNEE REPLACED
AND REVISED, MY RIGHT KNEE.
MY LUMBAR SPINE AND CERVICAL
SPINE, C3 TO T1, L4 TO S1 DISKS
HAVE BEEN REPLACED AND FUSED.
WHEN I FIRST FOUND OUT ABOUT THE
UCSF TRIAL ENTAILING THREE BRAIN
SURGERIES, IT SCARED THE HELL
OUT OF ME.
I RAN AT FIRST.
BUT THEN MY PAIN GOT SO BAD AND
SO BRUTAL THAT I HAD NO OTHER
CHOICE BUT TO GO THROUGH WITH
THE TRIAL, AND NOW I WISH I
WOULDN'T HAVE WAITED.
I WAITED A YEAR AND A HALF
BEFORE ACTUALLY GOING THROUGH
WITH IT, AND I WISH I WOULD HAVE
DONE IT A LOT SOONER.
THE DESCRIPTION OF MY PAIN AT
ITS WORST, THIS IS ALL ON THE
INSIDE, NO ONE CAN SEE IT UNLESS
THEY SEE ME IN IT.
I HAVE WHAT I CALL TWO LIGHTNING
BOLT RAZOR SNAKES THAT COME OUT
OF MY BIG TOES AND WREAK HAVOC
ALL UP AND DOWN MY LEGS AND INTO
MY LOW BACK.
I WOULD LITERALLY REACH DOWN TO
SEE IF I WAS CUT AND BLEEDING
WHEN THE SNAKES CAME OUT IN MY
LEGS.
I BELIEVE THAT WAS THE WORST OF
MY CRPS PAIN.
BRAIN MANUFACTURED PAIN, NO
CUTS, NO BRUISES, NOTHING AT ALL
TO SEE, WITH THE EXCEPTION OF
HOW I REACTED TO IT.
AT ONE POINT, JUST BEFORE PRASAD
AND DR. SHANE GAVE ME MY FIRST
PERMANENT -- MY IMPLANTS, I WAS
IN THE WORST PAIN OF MY LIFE,
WHICH IS WHAT I'M DESCRIBING
NOW.
I ALSO DEAL WITH RADICULAR
LUMBAR PAIN, RADICULAR NECK
CERVICAL PAIN, PERIPHERAL
NEUROPATHY, FIBROMYALGIA AND
GOUT PAIN.
I DON'T WISH CRPS ON ANY HUMAN
IN THE PLANET, NOT EVEN MY WORST
ENEMY.
THE BRAIN DISEASE HAS BEEN HELL
TO DEAL WITH FOR MY WIFE AND ME.
IT'S NOT JUST THE ONES THAT ARE
IN PAIN, IT'S YOUR LOVED ONES
AND COLLEAGUES TOO.
I'M IN A FACEBOOK GROUP CALLED
POSITIVITY WITH RSD OR CSRP.ORG.
THERE ARE SEVERAL OTHER SUPPORT
GROUPS FOR CRPS PATIENTS BUT FOR
ME, THIS WAS THE ONE, AND
THERE'S THOUSANDS OF US THAT
NEED HELP.
RECENTLY I WENT BACK TO WORK FOR
A RIDESHARING COMPANY WHEN I
CALLED MY DISABILITY LAWYER TO
FIND OUT THE DETAILS OF LEAVING
DISABILITY.
SHE WAS IMMEDIATELY TAKEN BACK.
I DIDN'T HEAR ONE WORD OUT OF
HER FOR ABOUT 20 SECONDS AND
THEN SHE SAYS, YOU'RE THE FIRST
ONE IN 25 YEARS TO EVER CALL AND
ASK HOW TO GET OFF DISABILITY,
NOT GET ON.
DURING THE 10-DAY TRIAL, I
BROUGHT MY GUITAR WITH ME, MY
LAPTOP AND A SMALL RECORDING
INTERFACE.
I'M WRITING A METAL SONG ABOUT
THE TRIAL ACTUALLY.
I WAS IN USCF HOSPITAL FOR 10
DAYS LIKE PRASAD SAID.
EVERY DAY WE TESTED THE
TEMPORARY 144 POINTS IN MY HEAD.
THE KAY AFTER THAT MY FIRST
TEMPORARY BRAIN SURGERY.
MY THOUGHTS WERE STAY POSITIVE
AND DO EVERYTHING THEY ASK OF
ME, AND I DID.
I CALLED THE WIRE ON MY HEAD MY
PREDATOR BRAID.
I MADE JOKES ABOUT IT AND GOT
THROUGH IT THE BEST I POSSIBLY
COULD.
THEY HAD ME PACING UP AND DOWN
THE HALLWAY IN THE HOSPITAL
WHILE I WAS TESTING.
WE HAD A HOT SAUCE TEST, WE HAD
SHAM TESTING.
MY PAIN JUMPED ALL OVER THE MAP
DURING SHAM TESTING.
THEN IN THE LAST TWO DAYS OF
TESTING, THE SIGNAL STARTED
WORKING AND KILLING MY PAIN.
I WAS BESIDE MYSELF.
IT WAS LIKE I'D LOST A BEST
FRIEND, AND THAT WAS THE PAIN.
I STILL HAVE PAIN SPIKES POP UP
SOMETIMES -- I DON'T HAVE ANY IN
A DAY, SOMETIMES I'LL HAVE THREE
OR FOUR, FIVE IN A WEEK.
AND I CAN FEEL THE ADAPTIVE
PROGRAM KICK ON AND TURN OFF THE
PAIN IN MY FEET.
I'M LIKE, IT STARTS TO GO UP AND
I'M LIKE, OH, HERE COMES THE
PAIN, AND THEN -- OOP, IT'S
GONE.
IT'S REALLY COOL.
I'M STANDING HERE RIGHT IN FRONT
OF YOU ALL AS LIVING PROOF THAT
DBS WORKS FOR PAIN.
PRASAD AND HIS TEAM AT UCF HAVE
GIVEN ME MY LIFE BACK, AND I'M
NOT SQUANDERING MY SECOND CHANCE
AT LIFE.
THANK YOU GUYS, AND THANK YOU,
PRASAD.
>> DR. ALI REZAI.
>> GOOD MORNING.
ED, YOU'RE WHY WE'RE ALL HERE,
SO THANK YOU FOR SHARING YOUR
EXPERIENCE.
FIRST SLIDE, IF I MAY, PLEASE.
SO I'D LIKE TO GIVE THE RESULTS
OF OUR DEEP BRAIN STIMULATION
AND FOCUSED ULTRASOUND
PROCEDURES FOR OPIOID USE
DISORDER.
I WANT TO THANK DR. VOLKOW,
DR. AKLIN, KEVIN WALTON, AND
JENNIFER WONG FOR THEIR SUPPORT.
IF IT WASN'T FOR KEVIN AND WILL
AND DR. VOLKOW, WE WOULD NOT BE
HERE.
SO FIVE YEARS AGO, THEY BELIEVED
IN THIS OPPORTUNITY TO PUSH
FORWARD THE FRONTIERS OF
NEUROMODULATION.
SO WE APPRECIATE THAT.
WITHOUT YOU, WE COULD NOT DO IT.
SO CAN YOU GET THE SLIDES GOING,
BY ANY CHANCE?
WILL YOU GIVE ME EXTRA TIME?
JUST KIDDING.
I'LL JUST START.
SO BASICALLY, THERE ARE MANY
NETWORKS IN THE BRAIN, CORTICAL
AND SUBCORTICAL NETWORKS IN THE
BRAIN THAT ARE INVOLVED IN THE
REWARD CIRCUITRY OF ADDICTION,
AND NEUROMODULATION CAN BE USED
FOR POTENTIAL ADJUNCTIVE
TREATMENT IN ADDITION TO
MEDICATIONS AND BEHAVIORAL
THERAPY.
SO YOU DELIVER MAGNETIC ENERGY
TO DIFFERENT NODES IN THE BRAIN
WITH TMS, YOU DELIVER ELECTRICAL
ENERGY WITH TDCS, AND WITH DEEP
BRAIN STIMULATION, AND YOU
DELIVER ULTRASOUND ENERGY.
SO ONE OF THE KEY ASPECTS FOR
DBS AND FOCUSED ULTRASOUND IS
THAT WE CAN DELIVER THE ENERGY
DEEP INTO THE BRAIN INTO THE
NUCLEUS ACCUMBENS.
SO THIS IS WHY WE STARTED THIS
STUDY, DECADES OF WORK WITH ABUM
KENS THAT SHOWS THE CIRCUITRY.
WE DECIDED TO EXPLORE DEEP BRAIN
STIMULATION FIRST OF THE NUCLEUS
ACCUMBENS FOR SEVERE OPIOID USE
DISORDER.
THIS IS BASED ON YEARS OF
RESEARCH PRECLINICALLY AND ALSO
SEVERAL PAPERS FROM GROUPS IN
EUROPE, IN CHINA, IN CANADA,
THAT THEY LOOKED AT DEEP BRAIN
STIMULATION FOR ALCOHOLISM,
SEVERE AUD AND OPIOID COCAINE
AND OTHER DISORDERS.
SO THAT'S LED TO NIDA SPONSORING
IN 2018 A UG STUDY LOOKING AT
DEEP BRAINSTEM LAITION
FEASIBILITY AND SAFETY STUDY OF
THE -- IN THE NUCLEUS ACCUMBENS.
AND WE STARTED THAT WITH A
FOUR-PATIENT -- ARE THE SLIDES
GOING TO GO OR SHOULD I JUST
CONTINUE?
OKAY.
SO WE DID A FOUR-PATIENT SAFETY
AND FEASIBILITY LOOKING AT
PEOPLE WITH SEVERE OPIOID USE
DISORDER AND THOSE WHO HAVE
FAILED MULTIPLE TREATMENTS,
MULTIPLE OVERDOSES AND WERE VERY
DISABLED AND THEY UNDERWENT THIS
STUDY.
FOUR PARTICIPANTS, YEARS OF
MEDICATION USE, THEY ALL HAD
MEDICATIONS FOR OPIOIDS.
SUBOXONE, METHADONE, AND
MULTIPLE OVERDOSES AND VERY
SEVERE.
AND THEIR RESULTS WERE VERY
PROMISING IN TERMS OF ACUTELY
BEING ABLE TO -- NO, I'M JUST
GOING -- IT'S OKAY.
BUT IT WAS WORKING EARLIER,
SO -- OKAY.
I'M OKAY, I'M OKAY.
I'M JUST GOING BY MEMORY.
SORRY.
WE'LL JUST IMPROVISE.
IS THAT OKAY?
SO BASICALLY, WHAT WE -- ONE
IMPORTANT THING WAS THAT DURING
THE SURGERY WITH THE BRAIN --
THANK YOU VERY MUCH!
OH, NO, I SEE IT THERE BUT I
DON'T SEE IT HERE.
OKAY.
THERE WE GO.
DO I GET THAT TIME BACK?
NO, I'M JUST KIDDING.
CAN I SEE IT HERE AS WELL IF
POSSIBLE?
CAN THEY SHOW IT ON THIS MONITOR
AS WELL?
OKAY, SO BASICALLY LOOKING AT AS
POTENTIAL ADJUNCTIVE TREATMENT,
MULTIPLE ENERGIES, TMS, TDCS,
DBS -- DEEP BRAIN STIMULATION WE
TALKED ABOUT STUDIES ACROSS THE
WORLD.
FEW PATIENTS, NOT RANDOMIZED
CONTROL TRIAL.
INITIAL UG NIDA SPONSORED STUDY,
2018, SEVERE OUD AND LIFE THREAT
LIFE-THREATENING OVERDOSES.
THIS IS THE PROTOCOL, INVOLVED
INPATIENT ASSESSMENTS.
AT BASELINE, AND THEN THE FDG
PET TO LOOK AT BRAIN METABOLISM
AND THEN LONG-TERM FOLLOW LN UPS
OUTPATIENTS IN THEIR NATURAL
ENVIRONMENT.
FOUR PATIENTS, MULTIPLE YEARS OF
DRUG USE, AND ON AVERAGE, THEY
TOOK SUBSTANCES ONE WEEK BEFORE
THEY WERE ENROLLED.
MANY, MANY SUBSTANCES.
TARGETING THE BRAIN, BILATERAL
NUCLEUS ACCUMBENS SEEN ON
IMAGING AND TRACTOGRAPHY.
HERE'S AN EXAMPLE, ACUTE
REDUCTIONS IN CREW INDUCED
CRAVING WITH ELECTROSTIMULATION
TURNED ON.
I HOPE THE VIDEO PLAYS.
CAN YOU TURN ON THE AUDIO,
PLEASE?
THANK YOU.
[INAUDIBLE]
>> SO ACUTELY, WITHIN SECONDS,
CRAVING DECREASED FOR THE
SUBSTANCE WITH Q INDUCTION.
THIS WAS VERY CONSISTENT ACROSS
THE SUBJECTS.
SO THE OUTCOMES, WELL-TOLERATED,
NO SERIOUS ADVERSE EFFECTS.
REDUCTION OF CRAVINGS AND
ANXIETY IN ALL PARTICIPANTS.
TWO PATIENTS HAD COMPLETE
ABSTINENCE, 1700 DAYS AND 1100
DAYS POST DBS, AND FDG-PET IN
THESE TWO INDIVIDUALS REVEALED
INCREASED GLUCOSE METABOLISM IN
THE FRONTAL REGION BEFORE AND
AFTER DBS, SMALL NUMBER.
CAUTION ABOUT CONCLUSIONS ON
THAT.
ONE PATIENT HAD DRUG RECURRENCE
USE, NO OVERDOSES BUT ACHIEVED
FOUR MONTHS OF ABSTINENCE AND
DISCONTINUED PARTICIPATION THREE
YEARS DUE TO PROTOCOL FATIGUE
AND NOT WANTING TO COME BACK AND
UNDERGO EVALUATIONS.
AND THE LAST PARTICIPANT WAS
EXPLANTED DUE TO PERSISTENT
NONCOMPLIANCE WITH THE STUDY.
SO DBS, THE UGUH PHASE INITIALLY
IS SAFE AND FEASIBLE FOR SEVERE
OUD.
RESULTS ARE ENCOURAGING OF
REDUCED CRAVING AND USE.
IT IS AN INVASIVE BRAIN
PROCEDURE.
BRAIN SURGERY HAS SIGNIFICANT
REQUIREMENTS FOR MAINTENANCE OF
THE IMPLANTS, BAT REAS CHANGES
AND PROBLEMS MANAGEMENT OF THE
DEVICE, HAVE TO COME BACK A LOT.
INTENSE PROTOCOL DEMANDS THAT
MADE THE STUDY RETENTION
PROBLEMATIC.
RECRUITMENT WAS A CHALLENGE,
RECRUITED FOUR PATIENTS OVER TWO
YEARS, SO IT WAS VERY DIFFICULT
TO FIND A LARGE POPULATION.
SCALING POTENTIAL IS LIMITED.
SO WE WANT TO EXPLORE OTHER
ASPECTS.
IN THE SAME TIME, THERE'S BEEN
CHANGES GOING ON WITH FOCUSED
ULTRASOUND IN THE WORLD OF
NEUROSURGERY, WHICH IS REA HAS Y
DRAMATICALLY CHANGED THE
LANDSCAPE OF PROCEDURES WE'RE
DOING AS NEUROSURGEONS.
IT'S A FOCUSED ULTRASOUND
SYSTEM.
YOU LIE IN MRI, HELMET COMES
OVER YOUR HEAD, IT HAS 1,000
ULTRASOUND PROBES THAT YOU CAN
BEAM AND TARGET ANYWHERE YOU
PRESCRIBE IN MRI CORTICALLY,
SUBCORTICALLY, THALAMUS.
15,000 PROCEDURES DONE
FDA-APPROVED STANDARD OF CARE
FOR PEOPLE WITH SEVERE TREMOR
AND PARKINSON'S.
IN FACT, LAST YEAR THERE WERE
MORE FOCUSED ULTRASOUNDS FOR
TREMOR THAN DBS.
SO THE FIELD IS CHANGING
DRAMATICALLY.
APPLICATIONS.
THE MOST COMMON STANDARD IS FOR
TREMOR IN PARKINSON'S, YOU MAKE
A SMALL LESION IN THE BRAIN.
SECOND APPLICATION, RAPIDLY
EXPLODING, IS TARGETED BLOOD
BRAIN OPENING WITH FOCUSED
ULTRASOUND FOR DRUG DELIVERY.
AND THEN THE ONE THAT WE HAVE
LOOKED AT MORE IS
NEUROMODULATION WITH LOW
INTENSITY FOCUSED BEAM DELIVERY.
SO THIS HAS BEEN SHOWN IN 100
PROCEDURES SO FAR, SO WE USED
INSIGHTEC HELMET, YOU LIE IN THE
MRI, HELMET COMES OVER YOUR
HEAD, IT'S A LOW INTENSITY
SYSTEM AND WE DELIVER THE
THOUSAND ULTRASOUND PROBES TO
THE PINPOINT AREA IN THE
ACCUMBENS AND DELIVER ULTRASOUND
ENERGY.
WHEN YOU'RE LOOKING AT THE HEART
OR -- THIS IS A THOUSAND OF THEM
BEING CONVERGED ON A POINT.
SO THIS LED US TO DO A SAFETY
STUDY.
WE DID NOT KNOW IF ULTRASOUND
HAS ANY IMPACT SAFETY OR OTHERS,
SO WE STARTED A SAFETY STUDY
WITH FDA.
FOUR PARTICIPANTS FROM
OUTPATIENT PROGRAM, UNILATERAL,
LET'S DO ONE SIDE AT A TIME TO
MAKE SURE IT'S SAFE ON THE
ACCUMBENS AND WE DEMONSTRATED IT
WAS SAFE AND WELL TOLERATED WITH
THE POTENTIAL SIGNAL FOR
REDUCING CRAVINGS IN 90 DAYS,
AND THAT GAVE US A DOSE-RESPONSE
CURVE AS WELL, SO WE OP OPTIMIZD
THE DOSE.
WHICH LED TO THE NEXT STUDY,
WITH IS LOOKING AT SAFETY AND
FEASIBILITY AND TOLERABILITY FOR
INDIVIDUALS WITH SEVERE OUD
THROUGH 90 DAYS PRIMARY END
POINT SAFETY, AND THEN LOOKING
AT SECONDARY OBJECTIVE
SUBSTANCE, CRAVING SUBSTANCE
USE, FUNCTIONAL CONNECTIVITY
WITH FMRI, AND THESE ARE
PATIENTS WHO WERE ALL ON
MEDICATIONS, SUBOXONE,
METHADONE, AND RECRUITED FROM
OUR 28-DAY RESIDENTIAL PROGRAM.
AND THIS STUDY, WE'RE GOING TO
REPRESENT EIGHT PATIENTS 90 DAYS
PLUS OUT COME.
BUT WE HAVE OVERALL 16 PATIENTS
IN THE STUDY.
THE DESIGN.
BASELINE, WE OBTAINED SAFETY
QUEUE INDUCED SUBSTANCE CRAVING
MOOD, EMOTIONAL FUNCTIONING,
COGNITIVE AND SUBSTANCE USE TOX,
URINE TOX.
CRAVING IS VERY IMPORTANT, QUEUE
INDUCED CRAVING, VISUAL CUES,
PROVIDE BASELINE AT MULTIPLE
TIME LINES AND PERSONALIZE TO
THE PATIENT'S INDIVIDUAL CRAVING
PROFILE.
AND THEN DURING THE PROCEDURE
NOW, WE DO BEHAVIORAL CRAVINGS
AS WE SHOWED AND NOW WE HAVE
GOGGLES THAT WE BEAM THE IMAGES,
PERSONALIZED TO THAT PATIENT, TO
GET THEIR DIGITAL SCALE AND
OBSERVE WHAT HAPPENS TO THEIR
CRAVINGS, AND THEN WE DO SHAM,
FIVE MINUTES.
WE DO FOUR 5-MINUTE BLOCKS FOR
TREATMENT AND ONE BLOCK OF
5-MINUTE SHAM FOR FDA
REQUIREMENTS, AND THEN WE
DELIVER THE ULTRASOUND TO THE
BILATERAL NUCLEUS ACCUMBENS, AND
THEN WE MONITOR DURING THE
TREATMENT SAFETY, CRAVINGS,
MOOD, COGNITIVE FUNCTION AND
FUNCTIONAL NEUROIMAGING, AND
THEN AFTERWARDS FROM DAY ONE, 7,
ALL THE WAY TO LONG TERM.
INITIALLY THE STUDY WAS ONLY 30
DAYS.
WE DID NOT EXPECT TO SEE CHANGES
AFTER 30 DAYS.
BUT BECAUSE OF THE RESPONSE, WE
EXTENDED IT TO NOW ONE YEAR AND
LONGER.
SO, PROCEDURE.
OUTPATIENT MRI SUITE, PATIENT
LIES IN MRI, HELMET COMES OVER
YOUR HEAD, WE USE A DENTAL MOLD
OR HEAD FRAME.
PATIENT PREFERENCE.
WE DO ANATOMICAL TARGETING OF
THE ACCUMBENS LIKE WE'VE DONE
FOR DEEP BRAIN STIMULATION THAT
REALLY GUIDED AN FOCUSED OUR
TARGETING TO THE MEDIAL
PREFRONTAL CORTEX.
PERSONALIZED CUES THAT THEY GET
ON THE TABLE ONCE THE CRAVINGS
ARE UP, THEN WE GIVE THE
ULTRASOUND TREATMENT.
IT TAKES ONE HOUR AND THEN THEY
GET OFF THE TABLE AND EAT FOOD
AND THEN THEY GO HOME.
THAT'S THE BASIC PROCEDURE.
CHARACTERISTICS OF THIGHS EIGHTT
SUBJECTS, SIGNIFICANT USE OF
HEROIN AND FENTANYL, 14 YEARS,
AND PRESCRIPTION OPIOIDS, 14
YEARS MEDIAN, AND THEN THEY ALSO
WITH THESE SEVERE PATIENTS HAVE
CO-MORBID METH, COCAINE, BENZO
AND OTHER PROFILES OF USE OF
MANY YEARS.
SEVEN OF THESE EIGHT HAD
MULTIPLE UNSUCCESSFUL ATTEMPTS
WITH INPATIENT, OUTPATIENT,
RESIDENTIAL, MEDIAN OF 4.
AND THEN THEY WOULD RELAPSE
OFTEN.
ONE PERSON, DESPITE 23 YEARS OF
USE, NEVER SOUGHT TREATMENT
UNTIL WHEN THEY CAME TO THE
OUTPATIENT TREATMENT CENTER
BASED ON THEIR FAMILY'S
INSISTENCE.
SO WHAT'S THE OUTCOME?
SAFETY MOST IMPORTANT THING.
SAFE AND WELL TOLERATED, 16
PATIENTS SO FAR BUT THIS FIRST
EIGHT, NO EXPECTED AEs OR
SAEs.
NO BRAIN CHANGES, NOT SEEING
HEMORRHAGE, HE DEME OR ANYTHING
THAT WE OBSERVED ON ANY OF THE
MULTIPLE MR SEQUENCE THAT WE DO.
AND THEN WE'RE NOT KNOCKING OUT
THE ACCUMBENS.
IT'S NOT A LESION, SO BASED ON
SHAPS, QUALITY OF LIFE AND OTHER
SCALES, WE'RE NOT SEEING THEY'RE
HAVING CHANGES WITH SATISFACTION
WITH SOCIAL ROLES, POSITIVE
AFFECT AND WELL-BEING, SO ARE WE
SOMEHOW LESIONING OR IMPACTING
THE ACCUMBENS ADVERSELY, BUT
WE'RE NOT, IT SEEMS LIKE, AT
THIS POINT.
WHAT ABOUT THE CUE INDUCED
CRAVINGS?
THAT WAS ONE OF OUR OUTCOMES
AFTER SAFETY, LOOKING AT
BASELINE, BASELINE EIGHT
PARTICIPANTS AND THIS IS SCALE,
ZERO TO 10.
THIS IS THE FUS PROCEDURE, DAY
1, 7, 30, 60 AND 90 DAYS WITH
REDUCTIONS IN CRAVINGS AND
THERE'S THE OUTLIERS RIGHT THERE
IN PLUSES.
THIS IS OPIOID KRIEFING,
BASELINE VERSUS POST-OP.
WHAT ABOUT METH AND COCAINE AND
BENZOS?
THIS IS THEIR AVERAGES, THIS IS
THE MEDIAN SORRY.
BASELINE, FUS AND UP TO 90 DAYS
AND COUNTING METH, COCAINE AND
BENZOS AND THEIR CRAVINGS FOR
THESE SUBSTANCES.
WHAT ABOUT CANNABIS, ALCOHOL AND
NICOTINE, WHICH ARE READILY
AVAILABLE VERSUS OTHER DRUGS?
BASICALLY SAME, INTERESTING
PROFILE THAT WE SAW REDUCTIONS.
NICOTINE WAS MORE RESISTANT BUT
THESE ARE INTERESTING
OBSERVATIONS.
WE'RE REPORTING 90 DAYS RIGHT
NOW FOR OUR PROTOCOL.
EMOTIONAL OUTCOMES.
ANXIETY, DEPRESSION AND MOOD AT
THIS TIME WE CAN SEE AT BASELINE
FOR THESE INDIVIDUALS BOX PLOTS
AND THEN PROCEDURE AND THEN 90
DAYS PRIMARY -- SECONDARY
OUTCOME THAT WE LOOKED AT IN
THESE INDIVIDUALS FOR DEPRESSION
AND ANXIETY.
AND THEN WHAT ABOUT SUBSTANCE
USE?
URINE TOX SUBSTANCE USE, EIGHT
PARTICIPANTS, SO WE CAN SEE
GREEN INDICATES NEGATIVE, RED IS
POSITIVE, SO THEY HAD
PARTICIPANT 3, 5 AND 7 -- 6,
RATHER, HAD ISOLATED USE.
INTERESTING THE USE WAS REDUCED
SIGNIFICANTLY BUT THEY DID USE,
3 OUT OF 8.
-- PROTOCOL ALLOWED US TO DO
REPEAT ULTRASOUND.
SO PARTICIPANT NUMBER 6, WE
TREATED HIM AGAIN, AND THEN HIS
CRAVINGS WENT DOWN AND SO FAR
HE'S ALSO ABSTINENT.
SO THOSE ARE THE URINE TOX
RESULTS.
WHAT ABOUT SUBJECTIVE OUTCOMES?
POST FUS PARTICIPANT FEEDBACK.
THIS IS PATIENT RESPONSES AND
PROVIDER OBSERVATIONS.
ON THE TABLE EVERY PARTICIPANT
SAYS I AM NOT CONNECTING TO THE
CUES.
THE IMAGES OF HEROIN, OF PILLS,
OF COCAINE, IT'S NOT MAKING
SENSE TO THEM.
SO IT SEEMS LIKE ACUTE
DISCONNECTION TO THEM, AND
THEY'RE ALL CONFUSED, THEY SAY
WHAT HAPPENED?
I'M NOT UNDERSTANDING WHAT'S
GOING ON.
SIGNIFICANT DECREASE IN
CRAVINGS, ACUTELY ON THE TABLE,
COMPARED TO SHAM.
WE DID NOT HAVE AS MUCH WITH
SHAM.
AND THEN REDUCED THOUGHTS AND
DREAMS RELATED TO ALCOHOL AND
MANY OTHER ASPECTS THAT ARE
IMPROVED WE'RE OBSERVING RIGHT
NOW.
THIS IS JUST INITIAL RESULTS.
AND STABLE DESIRE, NO CHANGE IN
PLEASURES OF LIFE, FOOD, THIS IS
VERY IMPORTANT TO MAKE SURE
WE'RE NOT IMPACTING THOSE.
ENHANCED MOOD, SHARPER FOCUS,
AND MANY ARE ENGAGING WITH THEIR
FAMILIES, CHILD PROTECTIVE
SERVICES GIVING THEIR KIDS BACK
TO THEM, AND LIFE ENGAGEMENT,
EDUCATION, OTHER -- SO IT SEEMS
INTERESTING IN TERMS OF THEIR
RESPONSE.
I'LL GIVE YOU TWO QUICK VIDEOS
IF I MAY.
THIS IS TWO PARTICIPANTS TALKING
ABOUT THEIR CRAVINGS BEFORE AND
AFTER THE FUS PROCEDURE.
CAN YOU TURN THE VOLUME UP,
PLEASE.
AFTER THE PROCEDURE, IT WAS JUST
LIKE I FELT BAD FOR THE PERSON
THAT I WAS TO BE IN THAT
SITUATION.
>> AND I COULD NOT CONNECT WITH
THE PHOTOS ANYMORE, LIKE, I'M
TRYING TO ELICIT SOME TYPE OF
FEELING THAT I KNEW, LIKE,
PREVIOUSLY WOULD EXCITE ME OR
ENTICE ME TO USE, AND I REALLY
JUST COULDN'T CONNECT WITH IT.
YOU KNOW, I THINK THIS IS --
THIS IS LIKE AN EXTRA TOOL FOR
ME, YOU KNOW?
I THINK THIS IS -- --
>> I DON'T KNOW WHAT TO DO HERE
BUT ANYHOW, SORRY.
THEN HOW ABOUT FUNCTIONAL MRI?
I'LL BE DONE IN TWO MINUTES.
SO BASICALLY I WANT TO CAUTION
IS ONLY SEVEN PARTICIPANTS AND
IT'S OBSERVATIONAL, SO WE'RE
ASSESSING IT LOOKING AT CHANGES
IN FUNCTIONAL CONNECTIVITY WITH
THE SEED AND THE BILATERAL
ACCUMBENS TO LOOK AT
CORRELATIONS IN THE REST OF THE
BRAIN BEFORE AND AFTER
ULTRASOUND.
YOU CAN SEE HERE A BASELINE
PROFILE OF POSITIVE CONNECTIVITY
AND CORRELATIONS WITH THE
DIFFERENT PARTS OF THE NETWORK.
SEVEN DAYS LATER, WE SAW AN
INCREASE OBSERVATION OF ACTIVITY
OF ACCUMBENS BILATERAL WITH ACC
AND REDUCTIONS OF PFC AND
POSTERIOR CORTEX.
30 DAYS WE SAW REDUCTION IN NAC
CONNECTIVE WITH ACC AND
SIGNIFICANT REDUCTION GOING DOWN
IN THE PFC.
SO WE'RE ANALYZING, DOING A
60-DAY ANALYSIS AS WELL BUT
THERE SEEMS TO BE CHANGES IN
SOME OF THE NETWORKS WHICH WE
NEED TO UNDERSTAND BETTER BUT
THESE ARE OBSERVATIONS WITH THE
FUNCTIONAL CONNECTIVITY, CON
COME AT THAT PARTICULAR TIME
REDUCTION IN CRAVINGS AND USE.
COUPLE OTHER THINGS.
WEARABLES IS IMPORTANT, WE ALSO
LOOKED AT ANOTHER STUDY WITH
THESE PATIENTS.
HEART RATE AUTONOMIC NERVOUS
SYSTEM, WHAT HAPPENS OVER TIME
TO THEIR HEART RATE, HEART RATE
VARIABILITY AND SUBJECTIVE
ELEMENTS LINKED TO AN APP THAT
THEY USE AND AGAIN CAUTION EARLY
RESULTS, BUT WE'RE SEEING
STATISTICALLY SIGNIFICANT
INCREASE IN HEART RATE
VARIABILITY OVER THE 60 TO 90
DAYS AS COMPARED TO BASELINES
FOR HRV, AND ALSO SUBJECTIVE
IMPROVEMENTS OF SLEEP QUALITY
AND WE'RE ANALYZING MUCH MORE
DATA BUT THIS IS JUST AN INITIAL
PEAK INTO THIS DATA, WHICH IS
VERY EXTENSIVE.
JUST ANOTHER CONCEPT ABOUT METH.
THERE IS NO MEDICATION FOR METH.
BIG PROBLEM.
WE DID ONE PATIENT WHERE WE HAD
A 26-YEAR-OLD MALE WITH 13 YEAR
HISTORY OF METH.
SEVERAL UNSUCCESSFUL INPATIENT,
OUTPATIENT, RESIDENTIAL.
PAST HISTORY OF EXCESSIVE
ALCOHOL USE AND CAN SEE CRAVINGS
SUBSTANTIALLY DECREASED 90 DAYS
AND IS STILL COUNTING BEYOND
THAT AND URINE TOX HAS BEEN
NEGATIVE, AND THIS INDIVIDUAL
TOOK METH EVERY WEEK SINCE AGE
13.
SO IT'S ONE CASE, WE WANT TO DO
A LARGER STUDY WITH METH BUT IT
SEEMS TO BE COVERING MULTIPLE
SUBSTANCES SO FAR.
SUMMARY.
BILATERAL ACCUMBENS ULTRASOUND
SEEMS TO BE SAFE AND WELL
TOLERATED FOR THREE YEARS WE'VE
BEEN DOING IT WITH NO UNEXPECTED
EA ES OR SAEs.
WE OBSERVED IMMEDIATE REDUCTIONS
IN CRAVINGS THAT YOU DON'T SEE
WITH SHAM, AFTER ONE 20-MINUTE
TREATMENT, REDUCTION WAS NOT
OBSERVED CONSISTENTLY WITH SHAM,
AND WE'RE SEEING WHAT WAS
SURPRISING TO US THE NEXT DAY
AND CONTINUING VERY SUSTAINED
REDUCTIONS OF CRAVINGS FOR
OPIOID AND METH AND COCAINE AND
BENZO AND OTHER SUBSTANCES AND
COUNTING.
URINE TOX CONFIRMED NO DRUG USE
IN FIVE OF EIGHT PARTICIPANTS.
AND WITH PRIMARY OUD AT 90 DAYS
OUTCOMES AND WE'RE CONTINUING
OBSERVATIONS, SO FAR THE
PATTERNS ARE CONSISTENT FOR
THESE INDIVIDUALS, WE'RE GOING .
NO AEs, NO ADVERSE REDUCTIONS
IN NATURALLY RY REINFORCING AND
PLEASURABLE BEHAVIORS --
OBSERVED BY THEIR PATIENTS AND
CARE PROVIDERS.
NEXT STEPS, LONG TERM FOLLOW-UP
ASSESSMENT, 16 PATIENTS, WE'LL
CONTINUE TO FOLLOW THEM UP
6 MONTHS AND 12 MONTHS, AND
WE'RE INITIATING WITH NIDA
SUPPORT A RANDOMIZED DOUBLE
BLIND SHAM CONTROLLED CLINICAL
TRIAL, WE RECEIVED FDA APPROVAL
IN DECEMBER, IRB APPROVAL IN
JANUARY AND ENROLLING THE FIRST
PATIENT NEXT MONTH.
WE NEED TO UNDERSTAND WHAT'S
GOING ON WITH THE MECHANISMS OF
THIS.
ONE 15, 20 MINUTE TREATMENT IS
OBTAINING SUSTAINED CRAVING AND
USE REDUCTIONS.
SO OVERALL SUMMARY.
BOTH DBS AND FUS METHODS MAY
HAVE A UTILITY AS AN ADJUNCTIVE
TREATMENT FOR OPIOID USE.
DBS, WHILE EFFECTIVE, HAS
LIMITATIONS.
AND SCALABILITY IS A PROBLEM,
AND IT'S INVASIVE.
FOUR PATIENTS IN TWO YEARS, WE
ENROLLED 16 PATIENTS FOR
ULTRASOUND IN TWO YEARS.
FUS MAY CIRCUMVENT THESE
LIMITATIONS WITH GREATER SAFETY
PROFILE AND POTENTIAL FOR
WIDESPREAD USE, BUT WE NEED TO
DO MORE RESEARCH.
THIS CANNOT BE DONE WITHOUT
DR. MAHONEY RIGHT THERE AND
DR. THOMPSON-LAKE, THEY'RE THE
ONES THAT DO ALL THE HEAVY LIFT,
AND WE APPRECIATE VERY MUCH THE
SUPPORT AND GUIDANCE FROM DRS.
VOLKOW, AKLIN, WANG AND WONG A.
THANK YOU VERY MUCH.
>> SO THANK YOU VERY MUCH.
WE HAVE TIME FOR QUESTIONS, IF
THERE ARE ANY QUESTIONS, THERE
ARE MICROPHONES ALONGSIDE THE
WALL HERE.
THANK YOU, GENTLEMEN, FOR THAT
FASCINATING SET OF
PRESENTATIONS.
IT REALLY HIGHLIGHTS HOW
IMPORTANT THESE TREATMENT
MODALITIES ARE ACROSS THE
CONTINUUM.
SO VERY NICELY DONE.
WE DO HAVE A QUESTION.
>> THAT WAS AMAZING.
WONDERFUL DATA.
SO JUST WONDERING IF YOU MIGHT
WANT TO CHALLENGE THE
INDIVIDUALS WITH A STRESSOR, AND
NOT NECESSARILY A DRUG CHALLENGE
BUT OF COURSE THE CIRCUITS ARE A
LITTLE DIFFERENT FOR THOSE.
THE OTHER THING IS, I WONDERED
IF YOU MEASURED BODY WEIGHT IN
YOUR PATIENTS FROM THE BEGINNING
TO THE END OF YOUR STUDY.
>> GREAT QUESTION.
BODY WEIGHTS, I HAVE TO GET BACK
TO YOU.
WE HAVE IT, I HAVE TO GET BACK
TO TO SEE IF THERE'S ANY CHANGE.
I DON'T THINK THERE'S BEEN ANY
SIGNIFICANT CHANGE IN THAT
REGARD.
BUT REGARDING THE STRESSORS, WE
DID CUE-INDUCED ACTIVATION, SO
THAT WAS A STRESSOR FOR THEM.
IN FACT, ONE PATIENT WHO REAL
RELAPSED, WE DECIDE FOR SAFETY
NOT TO DO CUES ANYMORE, BECAUSE
THEY WERE RELAPSING WE DIDN'T
WANT TO GET THEM FURTHER
AMPLIFIED SO CUES WERE
STRESSORS.
>> GREAT PRESENTATIONS.
REALLY SPECTACULAR, EXTREMELY
EXCITING.
MY QUESTION IS GOING TO GO FOR
OPIOID USE DISORDER.
YOU HAD I THINK IT WAS TWO OR
THREE PATIENTS THAT DID RELAPSE.
DID YOU ASK THEM WHEN THEY WERE
TAKING THE DRUGS, DID THEY FEEL
DIFFERENTLY ON THE EFFECTS OF
INTOXICATION?
>> IB DE INDEED THEY DID.
A COUPLE OF THEM BASICALLY SAID
THEY JUST WENT THROUGH IT, THEY
WERE PARTYING WITH FRIENDS AND
THEY WERE INTERACTING, SO THE
CRAVING WAS REDUCED IN THEM,
WHICH IS INTERESTING.
SO IT WAS MAYBE BEHAVIORAL BUT
THEY DID SAY THAT THEY DID TO
THE FEEL THE SAME.
SO WE NEED TO EXPLORE THAT
FURTHER.
BUT THEIR CRAVINGS IS THE MOST
CONSISTENT REDUCTION THAT WE SEE
IN THEM.
AND THEY ALL SAID THAT I TOOK IT
BUT I DON'T KNOW WHY I TOOK IT.
>> I HAVE A QUESTION OVER HERE
IF THAT'S OKAY.
GREAT PRESENTATIONS AND SPECIAL
THANK YOU TO EDWARD FOR SHARING
YOUR STORY.
IT WAS AMAZING, A MOTIVATING
STORY.
DR. REZAI, YOUR THOUGHTS ABOUT
SCALABILITY OF FOCUSED
ULTRASOUND.
DO YOU SEE THIS AS A PROCEDURE
THAT WILL ALWAYS HAVE TO BE DONE
BY NEUROSURGEONS, AND ALSO CAN
IT BE SCALED OUT TO SMALLER
HOSPITALS AND OUTPATIENT
CLINICS?
>> GREAT QUESTION.
I DO THINK THIS NEEDS TO BE DONE
ULTIMATELY BY NON-NEUROSURGEONS
TO SCALE.
THERE ARE DIFFERENT TYPES OF
ULTRASOUND UNITS LIKE A TMS
UNIT.
SO I THINK THIS NEEDS TO BE
EXPLORED, AND THIS NEEDS TO BE
DONE, IN OUR OPINION, IN THE
CLINIC BY ADDICTION SPECIALISTS.
SO I THINK THE KEY THING IS IT'S
NONINVASIVE, AND IT CAN BE LIKE
A TMS SYSTEM.
SO WE SHOULD MOVE IT AWAY FROM
NEUROSURGEONS OVER TIME.
>> THANK YOU.
>> HI.
I FIRST WANT TO JUST THANK ED
FOR SHARING YOUR STORY.
IT WAS VERY MOVING, AND I REALLY
APPRECIATE YOU SHARING IT WITH
US.
AND THEN I HAD A QUESTION ABOUT
THE USE OF THE FOCUSED
ULTRASOUND ON OPIOID USE
DISORDER.
DID YOU HAVE ANY REPORTED
CHANGES IN LIKE FOOD CRAVINGS OR
APPETITE?
>> GREAT QUESTION.
WE SHOWED THOSE OUTCOMES.
THOSE WERE IMPORTANT.
WE WANT TO MAKE SURE WE'RE NOT
KNOCKING OUT THE ACCUMBENS OR
LESIONS IT, ALTHOUGH WE DIDN'T
ANYTHING.
WE DID NOT SEE CHANGES IN THOSE
OR OTHER PLEASURABLE ACTIVITIES.
ALL OF THEM, THEY WERE NPO FOR
THE PROCEDURE, WITHOUT FOOD, AND
THEY WALKED OFF THE TABLE AND
THEY SAID, GIVE ME A CUP OF
COFFEE AND A SANDWICH.
SO WE HAVE NOT OBSERVED THAT,
WHICH IS VERY IMPORTANT FOR US.
IT'S A GREAT QUESTION BUT WE
HAVE NOT OBSERVED THOSE IMPACTS.
>> I HAVE A QUESTION OVER HERE.
THANK YOU FOR YOUR PRESENTATION.
MY NAME IS ANNA FROM UNIVERSITY
OF PITTSBURGH.
ED, YOU HAD KIND OF HINTED AT
THIS AND ALSO SOME OF THE
RESEARCHERS TOO, BUT YOU TALKED
ABOUT HOW LOSING THE PAIN SO
QUICKLY WAS LIKE LOSING A
FRIEND, AND THEN SOME OF THE
OUDs HAD ALSO TALKED ABOUT
THAT.
LIKE IT WAS A QUICK -- SOMETHING
VERY QUICK THAT DISAPPEARED ALL
OF A SUDDEN, AND THEY COULDN'T
FEEL THE CONNECTION TO THE CUES
ANYMORE, LIKE YOU DIDN'T HAVE
YOUR PAIN ANYMORE.
DO YOU, ED, AND THEN ALSO FROM A
RESEARCH PE PERSPECTIVE THE OTHS
SEE THAT BEING SOMETHING WITH
THESE TYPES OF INTERVENTIONS
THAT YOU'LL HAVE TO DEAL WITH IN
TERMS OF LIKE HELPING TO KIND OF
CREATE A NEW SELF VERY QUICKLY,
WHICH MIGHT NOT HAPPEN IN A
TRADITIONAL INTERVENTION?
>> IT WAS -- IT WAS ALMOST
DEPRESSING AT FIRST.
IT WAS REALLY STRANGE FOR PAIN
TO BE GONE, BECAUSE I'D BEEN IN
PAIN SINCE I WAS 14 YEARS OLD.
AND WHEN IT WAS GONE, IT WAS
EUPHORIC.
I MEAN, I LITERALLY FELT OUT OF
BODY AT THE BEGINNING.
BUT IT PASSED, AND WENT AWAY.
IT WAS DEFINITELY AN UNEXPECTED
FEELING.
>> HI.
I'D LIKE TO THANK EDWARD AS
WELL.
I THINK IT'S BEEN REALLY
HELPFUL.
I'M JUST WONDERING WITH THE
INVESTIGATORS BOTH FROM THE
STANDPOINT OF SUBSTANCE USE
DISORDER AND CRPS, THERE ARE SO
MANY POTENTIAL MENTAL HEALTH
COMORBIDITIES OR PHYSICAL
COMORBIDITIES THAT COULD GO
ALONG WITH THESE PROBLEMS, AND
I'M WONDERING IN THE PATIENTS
THAT YOU HAVE STUDIED OR
ENROLLED SO FAR, WHAT KIND OF A
PROFILE OR WHAT KIND OF A
SCREENING DID YOU DO IN ORDER TO
COME UP WITH THE INDIVIDUALS, OR
ARE YOU CONSIDERING THAT WHEN
YOU LOOK AT THE PATIENTS THAT
YOU'RE TREATING?
>> THANKS, THAT'S A GREAT
QUESTION.
OUR INCLUSION CRITERIA WAS, YOU
WANT TO INCLUDE A LARGE
POPULATION OF PEOPLE BUT YOU
WANT TO BE SPECIFIC AND
GENERALIZABLE, SO WE FOCUSED ON
NEUROPATHIC PAIN.
SO ANYONE WITH AN IDENTIFIABLE
NERVE INJURY CAUSING PAIN.
NONETHELESS THAT'S STILL
HETEROGENEOUS BUT EVERY PATIENT
UNDERWENT A FULL PSYCHOLOGICAL
EVALUATION TO MAKE SURE THERE
WERE NO OTHER UNTREATED
PSYCHOLOGICAL COMORBIDITIES.
IF SO, THEY COULD HAVE THAT
OPTIMIZED.
THEY UNDERWENT ALSO BRAIN MRI TO
MAKE SURE IT WAS SAFE TO TARGET,
IF THEY HAD ANY OTHER IMPLANTED
HARDWARE, THEY WERE NOT A
CANDIDATE UNFORTUNATELY.
WELL, THAT'S NOT TRUE BECAUSE ED
HAS A SPINAL CORD STIMULATOR,
BUT IF THEY'D HAD ANY PAIN BRAIN
HARDWARE OR PACEMAKER.
I THINK THE BIGGEST CRITICISM I
WOULD HAVE OF MYSELF AND OUR
STUDY IS WE'RE LOOKING FOR FOLKS
THAT VO CHRO HAVE CHRONIC PAIN E
STILL ACTIVE AND ABLE ENOUGH TO
PARTICIPATE IN A CLINICAL TRIAL,
WHICH SEEMS LIKE A
CONTRADICTION.
SO I THINK IT'S IMPORTANT TO
STUDY A LARGER POPULATION, BUT
TO DO SO IN A WAY THAT WE CAN
GENERALIZE.
>> FOR US IT'S SIMILAR BUT I
THINK IT WAS THE STANDARD DSM
CRITERIA, NO OTHER ONES EXCEPT
ANXIETY AND DEPRESSION, AND
THESE WERE INDIVIDUALS THAT WERE
KNOWN TO THE BEHAVIORAL TEAM, TO
THE ADDICTION MANAGEMENT TEAM.
THEY KNEW THEM REALLY WELL.
THAT'S VERY IMPORTANT.
AND WE ALSO RULED OUT PEOPLE
WITH PERSONALITY DISORDERS AT
THIS POINT.
SO UNDERGOING THIS.
SO VERY SIMILAR, BUT IT WAS
MANAGED BY A VERY EXPERT TEAM
THAT KNEW THESE PATIENT REALLY
WELL.
>> ONE FINAL QUESTION.
DR. VOLKOW.
>> I APOLOGIZE FOR ASKING AGAIN,
I WAS LOOKING TO SEE SOMEONE
ELSE, BUT I ALSO WANT TO THANK
YOU, EDWARD, FOR COMING HERE AND
SPEAKING TO US OF YOUR
EXPERIENCE.
AND REALLY COMMEND YOU FOR YOUR
COURAGE AND CONGRATULATIONS.
THIS IS QUITE REMARKABLE, SO
BEST OF SUCCESS.
>> THANK YOU.
>> I WILL SAY SOMETHING THAT
ACTUALLY LED ME TO A QUESTION
FOR DR. REZAI.
YOU MENTIONED THAT YOU WERE
THINKING THE PROCESS OF BRINGING
DOWN YOUR ANALGESIC DRUGS, SO
THAT LED ME TO ASK THE QUESTION
TO DR. REZAI, IN THOSE PATIENTS
THAT ARE STABLE, IS THERE A
DISCUSSION OF BRINGING DOWN
THEIR MEDICATIONS FOR OPIOID USE
DISORDERS?
WHAT ARE THE PLANS?
>> THAT'S A GREAT QUESTION.
I THINK AT THIS POINT, WHEN THEY
WERE ENROLLED, THEY WERE STABLE
ON THEIR MEDICATIONS FOR OPIOID
USE, BUT WE HAVE NOT MADE
CHANGES AT THIS POINT BUT WE'RE
IN ACTIVE DISCUSSIONS WITH THE
ADDICTION MANAGEMENT TEAM, SO
THERE'S OPPORTUNITIES TO REDUCE
IT.
BUT AT THIS POINT, WE HAVE NOT.
WE KEPT THEM IN THE SAME DOSES.
WE FOLLOWED THE CLINICAL
GUIDELINES OF THE ADDICTION
SPECIALISTS AT THIS POINT.
WE HAVE NOT DONE THAT.
BUT GREAT QUESTION.
WE NEED TO MAYBE LOOK AT THAT AS
WELL.
>> WELL, WE ARE AT TIME.
I WANT TO THANK THE PANELISTS, I
WANT TO THANK THE ORGANIZERS FOR
TODAY'S MEETING AND PLENARY
SESSION.
THANK YOU VERY MUCH.
AND THANK YOU FOR YOUR
PARTICIPATION.
>> I WANTED TO THANK AGAIN DRS.
AKLIN, REZAI, SHIRVALKAR AND
MR. MOWERY.
WHAT A POWERFUL TESTIMONY.
I HOPE YOU CAN SEE OUR HEAL
RESEARCH CAN HAVE A REAL IMPACT
AND I HOPE YOU TAKE THAT AWAY AS
MORE MOTIVATION FOR YOUR OWN
RESEARCH.
SO NOW WE HAVE A RESEARCH
PROGRAM UPDATE FROM THE BACK
PAIN CONSORTIUM OR BACPAC.
WELCOME TO THE STAGE DRS. SOWA,
TORRES ESPIN, MAUCK AND ANSTROM
TO PRESENT THEIR WORK.
>> THANK YOU SO MUCH.
IT IS AN HONOR AND A PRIVILEGE
TO OPEN THIS UP ON BEHALF OF THE
BACPAC INVESTIGATORS.
I'M GOING TO START OFF BY GIVING
AN OVERVIEW OF WHAT WE HAVE
ACCOMPLISHED AND WHAT WE HAVE
SET OUT TO DO IN THE CONSORTIUM,
BUT ALSO IMPORTANTLY, WHAT WE
HAVE THAT WE WILL BE ABLE TO
SHARE WITH THE HEAL COMMUNITY AS
WELL AS THE COMMUNITY AT LARGE.
I THINK WHAT YOU'LL SEE AND
APPRECIATE IS THERE IS GOING TO
BE A MASSIVE AMOUNT OF
PHENOTYPING INFORMATION THAT
HELPS US BETTER UNDERSTAND THE
EXPERIENCE CHRONIC LOW BACK
PAIN.
SO THE BACPAC MISSION WITHIN THE
HEAL UMBRELLA IS TRANSLATIONAL
PATIENT-CENTERED TO ADDRESS
EFFECTIVE AND PERSONALIZED
THERAPIES FOR CHRONIC LOW BACK
PAIN.
SO EACH OF THESE PIECES OF THE
MISSION IS VERY, VERY
INTENTIONAL.
WE HAVE TAKEN THE OPPORTUNITY TO
ENSURE THAT WE HAVE PEOPLE WITH
LIVED EXPERIENCES CONTRIBUTING
TO THE DESIGN OF THE WAY WE
COLLECT ALL OF THE INFORMATION,
AND NOW MORE RECENTLY, THE WAY
WE ARE ANALYZING AND
INTERPRETING THE INFORMATION
THAT WE HAVE.
SO THAT WAS VERY INTENTIONAL.
IT'S ALSO BEEN VERY INTENTIONAL
TO MAKE SURE THAT WE ARE
APPROACHING PERSONALIZED
THERAPIES.
AS YOU'RE PROBABLY FAMILIAR,
CHRONIC LOW BACK PAIN BEING A
MAJOR DRIVER OF DISABILITY AS
WELL AS SUBSTANCE USE, OUR
APPROACH FROM THE BEGINNING IN
THE CONSORTIUM WAS TO ENSURE
THAT WE DID NOT SET OUT TO PROVE
WHAT WE THINK WE KNEW.
THIS WAS A THEME THAT CAME UP
AGAIN AND AGAIN AS WE WERE
SETTING UP OUR DATA COLLECTION
METHODS.
INSTEAD, WE REALIZE THAT MUCH OF
THE CLINICAL FAILURE IN THE
TREATMENT OF CHRONIC LOW BACK
PAIN IS NOT NECESSARILY BECAUSE
WE DON'T HAVE GOOD TREATMENTS.
BUT IT'S WE DON'T KNOW IN WHOM
TO USE WHAT TREATMENTS WHEN.
SO THE REAL KEY FOR BACPAC IS TO
IDENTIFY THE RIGHT TREATMENT FOR
THE RIGHT PATIENT AT THE RIGHT
TIME, BECAUSE WHEN WE DON'T DO
THAT, THERE'S A LOT OF
FRUSTRATION OF BOTH THE PATIENT
AND THE CLINICIAN AND THINGS GO
DOWN THE WRONG DIRECTION.
SO THAT'S THE PRIMARY GAP.
OUR OBJECTIVES ARE SHOWN HERE TO
DEVELOP A THEORETICAL MODEL,
IDENTIFY FACTORS THAT ARE
PREDICTIVE OF TREATMENT
EFFECTIVENESS, AND THEN
ULTIMATELY TO DEVELOP AN
ALGORITHM.
SO WE INTENTIONALLY CAST THE NET
VERY BROADLY.
THERE ARE CERTAINLY
HYPOTHESIS-DRIVEN DATA
COLLECTION PROCEDURES AND TRIALS
WITHIN BACPAC, BUT THERE WAS
AGREEMENT EARLY ON TO LET THE
DATA TELL US THINGS WE DIDN'T
KNOW OR COULDN'T HAVE
ANTICIPATED LOOKING FOR IN THE
PAST.
AND WE'RE REALLY THANKFUL REALLY
TO NIH FOR GIVING US THE FREEDOM
AND THE OPPORTUNITY TO DO THIS
SO THAT WE IDENTIFY THINGS THAT
ARE TRULY PARADIGM CHANGING.
AND THAT IS VERY MUCH OUR
INTENT.
AND THIS HELPED FORM THE
QUESTIONS AND THE WAY THAT WE
HAVE APPROACHED THINGS
THROUGHOUT THE ENTIRETY OF
BACPAC.
WE ALSO WERE VERY INTENTIONAL IN
REACHING OUT TO COMMUNITIES THAT
WERE HISTORICALLY UNDERREP
RESENTED IN PAIN RESEARCH AND
BACK PAIN RESEARCH IN GENERAL.
DR. CHRIS KEL MENTIONED THIS
YESTERDAY BUT WE DID A LOT OF
DEDICATED OUTREACH TO MAKE SURE
THE DATA WE COLLECTED AND
PHENOTYPING WE WERE DOING WAS
TRULY REPRESENTATIVE OF THE
COMMUNITY WE WERE LOOKING TO
SERVE.
AND FINALLY, WE WERE LOOKING
VERY MUCH TO FIGURE OUT WHAT OF
THESE DEEP PHENOTYPING ASPECTS
ARE IMPORTANT, AND WHAT CAN BE
INCORPORATED IN THE CLINICAL
PRACTICE.
WHAT YOU'LL SEE IS WE'RE
COLLECTING A MASSIVE AMOUNT OF
DATA, AND THERE'S NO INTENT THAT
THIS WILL BE THINGS THAT CAN BE
DONE WITH EACH AND EVERY PERSON
THAT IS SEEKING CARE.
CARE INSTEAD,
WE'RE LOOKING FOR THE SIGNALS
AND WHAT ARE THE THINGS THAT ARE
GOING TO DIRECT US IN A
DIFFERENT DIRECTION.
SO THESE ARE THE BACPAC RESEARCH
SITES.
WE'RE WELL REP RESENTED ACROSS
THE COUNTRY.
THERE ARE THREE MECHANISTIC
RESEARCH CENTERS THAT ARE DOING
DEEP PHENOTYPING, CASTING THAT
NET BROAD AND DOING A MAJOR
MASSIVE AMOUNTS OF DATA
COLLECTION ON ALL ASPECTS OF THE
EXPERIENCE OF LOW BACK PAIN.
THOSE ARE AT THE UNIVERSITY OF
MICHIGAN, THE UNIVERSITY OF
PITTSBURGH AND THE UNIVERSITY OF
CALIFORNIA-SAN FRANCISCO.
WE ALSO HAVE SEVEN TECHNOLOGY
RESEARCH SITES THAT ARE
DEVELOPING NOVEL TECHNOLOGIES
FOR BOTH DIAGNOSIS AND
TREATMENT, AS WELL AS THREE
CLINICAL TRIALS.
WE'VE ALSO HAD THE OPPORTUNITY
TO DESIGN A VERY NOVEL
INNOVATIVE SMART TRIAL.
THE DESIGN OF THIS TRIAL WAS
CONFORMED BY CONSORTIUM MEMBERS
THROUGH CONSENSUS BUILDING BUT
ALSO WITH THE INPUT OF
STAKEHOLDERS WITH LIVED
EXPERIENCES.
AND THAT DEFINED THE WAY WE
APPROACH THIS TRIAL AND THE
TREATMENTS WE CHOSE TO STUDY.
WE CHOSE FOUR DIFFERENT TRE
TREATMENTS, NOT BECAUSE WE WERE
TRYING TO DETERMINE WHETHER THEY
WERE EFFECTIVE OR NOT.
WE KNEW THEY WERE EFFECTIVE.
WE WERE TRYING TO DETERMINE IN
WHOM THEY WOULD BE EFFECTIVE.
SO WE CHOSE THESE FOUR
TREATMENTS AND DID DEEP
PHENOTYPING OF ALL OF THE
PARTICIPANTS IN THE TRIAL TO
UNDERSTAND WHO WOULD RESPOND
BETTER.
THE FOUR TREATMENTS ARE SHOWN
HERE.
ENHANCED SELF-CARE, ACCEPTANCE
AND COMMITMENT THERAPY, A FORM
OF COGNITIVE BEHAVIORAL THERAPY,
EVIDENCE-BASED EXERCISE AND
MANUAL THERAPY, ESSENTIALLY
ENHANCED -- WE USED A PRAGMATIC
APPROACH TO IDENTIFY HOW
PATIENTS WERE DOING ON THAT
TREATMENT.
SO MUCH LIKE WE WOULD DO IN
CLINICAL PRACTICE, WE SAID IF
THE PATIENT IS DOING WELL, WE
MAINTAIN THEM ON THAT FIRST
RANDOMIZED TREATMENT.
IF THEY ARE DOING OKAY, WE MAY
AUGMENT THAT WITH ONE OF THE
OTHER THREE TREATMENTS, AND IF
THEY'RE DOING POORLY, THEN WE
WOULD RE-RANDOMIZE THEM TO ONE
OF THE OTHERS.
SO AGAIN, A PRAGMATIC APPROACH
THAT WOULD MIMIC WHAT WE WOULD
DO IN CLINICAL PRACTICE AND THEN
FOLLOWED THEM OUT.
WHAT YOU'LL HEAR ABOUT LATER IN
THE SESSION TODAY IS HOW WE'RE
STARTING TO PLACE PEOPLE WITHIN
THOSE SPACES AND THOSE
PHENOTYPES TO DEFINE WHO'S GOING
TO RESPOND BETTER TO DIFFERENT
TREATMENTS.
THESE ARE THE BEST TRIAL SITES,
AGAIN, WELL REPRESENTED ACROSS
THE COUNTRY, AND IT HAS BEEN AN
AMAZING COLLABORATION GETTING
EVERYONE TO ROW IN THE SAME
DIRECTION AND WORK TOGETHER IN
BOTH THE WAY WE COLLECT THE DATA
AND IN THE WAY THAT WE ARE
RECRUITING AND PARTNERING
TOGETHER.
IN TERMS OF HOW WE'RE
PHENOTYPING ACROSS THE
CONSORTIUM, WE'VE DONE A LOT OF
WORK TO HARMONIZE THIS.
WE'RE VERY MUCH USING THE
BIOBEHAVIORAL CONTEXT OF THE
PERSON WITH LOW BACK PAIN BY
COLLECTING INFORMATION ABOUT
SOCIAL DETERMINANTS, BEHAVIORS
AND LIFESTYLES, PAIN-RELATED
PSYCHOSOCIAL FACTORS, GENERAL
PSYCHOSOCIAL FACTORS, AND
INFORMATION ABOUT THE PAIN
CHARACTERISTICS AND QUALITIES
THEMSELVES, AND PUTTING THIS ALL
TOGETHER.
THIS JUST GIVES YOU A SENSE OF
THE PATIENT-REPORTED OUTCOMES
THAT WE ARE COLLECTING.
IN THE FIRST COLUMN THERE, YOU
CAN SEE WE'RE COLLECTING ALL OF
THE HEAL MINIMUM DATASET
PATIENT-REPORTED OUTCOMES.
IN ADDITION TO THAT, WE
HARMONIZED ACROSS THE CONSORTIUM
ADDITIONAL PATIENT-REPORTED
OUTCOMES THAT ARE RELEVANT
EITHER TO BACK PAIN OR THINGS
THAT ARE ADJACENT TO BACK PAIN
THAT WE WANTED TO MAKE SURE
EVERYONE WAS COLLECTING SO THAT
WE HAVE A CONSISTENT DATASET
THAT WAS HARMONIZED.
THIS GIVES YOU AN EXAMPLE OF
THAT HARMONIZATION OF
PATIENT-REPORTED OUTCOMES
BETWEEN WHAT WE'RE CONNECTING IN
THE MECHANISTIC RESEARCH CENTERS
AND ALSO COLLECTING IN THE BEST
TRIAL, SO THAT DEEP PHENOTYPING
WILL HAVE OVERLAP SO THAT WE CAN
COMPARE APPLES TO APPLES AS WE
LOOK AT THE DATA COMING OUT OF
ALL OF THESE DIFFERENT CENTERS.
SIMILARLY, THINGS ABOUT THE
EXPERIENCE OF PAIN AND
QUANTITATIVE MEASURES, THINGS
LIKE QUANTITATIVE SENSORY
TESTING, MONITORING PATIENTS AT
HOME, WE HARMONIZED THE WAY WE
WERE COLLECTING THAT DATA SO,
AGAIN, WE COULD COMPARE DATA
ACROSS THE CONSORTIUM.
I SEEM TO BE STUCK.
SO IF SOMEONE CAN HELP ADVANCE
THE SLIDES?
THE NEXT SLIDE THAT I'LL SHOW
YOU IS REPRESENTING THE THREE
MECHANISTIC RESEARCH CENTERS.
SO THE THREE MECHANISTIC
RESEARCH CENTERS, AGAIN, ARE
UNIVERSITY OF PITTSBURGH,
UNIVERSITY OF MICHIGAN, AS WELL
AS UCSF.
AND WHAT WE DID -- SORRY, IT'S
NOT WORKING AT ALL.
SO WHAT WE DID WAS WE HARMONIZED
OUR DATASETS WITHIN THE THREE
CONSORTIA, AND WE ALSO HAD
CERTAIN SEGMENTS OF THE
CONSORTIA WHERE WE WOULD
HARMONIZE BETWEEN TWO.
FOR EXAMPLE.
IN THE UNIVERSITY OF MICHIGAN,
THE UNIVERSITY OF PITTSBURGH, WE
WERE DOING ADDITIONAL
BIOSAMPLING IN ADDITION TO THE
PATIENT-REPORTED OUTCOMES.
UCSF AND MICHIGAN ARE
COLLABORATING DOING ADVANCED
IMAGING ANALYSIS AND COLLECTING
RICH DATASETS RELATED TO THAT.
NOW THAT THAT INFRASTRUCTURE IS
BUILT ACROSS THE MECHANISTIC
RESEARCH CENTERS, WE ARE VERY
HOPEFUL THAT NOW THAT WE HAVE
DONE THE BASELINE COLLECTION ON
ALL THESE HARMONIZED MEASURES,
THAT WE'LL BE ABLE TO FOLLOW
THIS VERY VALUABLE COHORT
FORWARD AS WE -- THERE YOU GO.
SO WE'LL BE ABLE TO FOLLOW THIS
VERY VALUABLE COHORT FORWARD AND
COLLECT DATA BEYOND THE ONE YEAR
FOLLOW-UP THAT WE'RE CURRENTLY
COLLECTING.
SO ROBUST DATA COLLECTION, AT
PITT WE NOW HAVE OVER 950
PARTICIPANTS AT UCSF, THEY HAVE
OVER 450 PARTICIPANTS, AS WELL
AS A REMOTE COHORT THAT IS NOW
MORE THAN 2400 PARTICIPANTS WITH
PATIENT-REPORTED OUTCOMES AND
ELECTRONIC MEDICAL RECORD DATA
AND AT MICHIGAN THEY'RE NOW WELL
OVER 420 PARTICIPANTS THAT HAVE
THE DEEP PHENOTYPING DATA AS
WELL AS PARTICIPATING IN THE
CLINICAL TRIAL.
I'LL GIVE YOU JUST A BIT OF A
SENSE OF THE PITT COHORT TO GIVE
YOU A SENSE OF WHO THESE PEOPLE
ARE WHO HAVE ENTERED INTO OUR
COHORT.
THE FIRST GRAPH THERE JUST PAIN
SCORE.
SO YOU CAN SEE A MODERATE RANGE
OF PAIN THAT IS RELATIVELY
CONSISTENT OVER TIME.
THAT Y AXIS IS EXPANDED THERE SO
THAT THAT DROP OR REGRESSION TO
THE MEAN THAT OCCURRED AFTER THE
BASELINE IS REALLY ONLY ABOUT A
POINT IN CHANGE AN IN PAIN SCOR.
SO MODERATE PAIN.
SIMILARLY, DISABILITY AS
MEASURED BY THE DISABILITY
INDEX, ALSO MODERATE AND
RELATIVELY CONSISTENT OVER THE
ONE-YEAR FOLLOW-UP.
WE ALSO DO HARMONIZATION OF HOW
WE ARE COLLECTING INFORMATION
ABOUT TREATMENTS.
WE RECOGNIZE THAT PEOPLE WITH
CHRONIC LOW BACK PAIN RECEIVE
DIFFERENT TYPES OF TREATMENTS,
AND SOMETIMES MULTIPLE
TREATMENTS AT ONCE.
SO WE HAVE HARMONIZED THE WAY
THAT WE'RE COLLECTING THAT
INFORMATION ACROSS THE
CONSORTIUM SO WE CAN COMPARE AND
CONTRAST.
AT PITT, WE SEE A VERY HIGH
PREDOMINENCE OF EXERCISE AS
BEING THE MAJOR TREATMENT THAT
PEOPLE ARE ENGAGING IN, FOLLOWED
BY NSAIDS, AND QUITE A BIT OF
MINDFULNESS AND MEDITATION IN
OUR COHORT AS WELL.
SO IT WILL BE INTERESTING AS THE
FULL DATASETS COME IN TO BE ABLE
TO SEE ALL OF THE DIFFERENT
TREATMENTS THAT PEOPLE ARE
RECEIVING.
WE'VE ALSO HARMONIZED THE
PHYSICAL EXAM MANEUVER SO WE
CREATED STANDARD OPERATING
PROCEDURES.
SO THAT THE WAY WE WERE
MEASURING RANGE OF MOTION WAS
THE SAME ACROSS ALL OF THE
DIFFERENT SITES IN THE
CONSORTIUM.
THIS IS WORK THAT IS LED BY
KEVIN BELL IN PITTSBURGH LACKING
AT LOOKINGAT USING SKIN SURFACEN
SENSORS THAT ARE WIRELESS WHERE
WE CAN COLLECT RANGE OF MOTION
OF MOTION, VELOCITY AND
ACCELERATION WITHIN SPINE
MOVEMENTS AND MEASURE ACTIVITY
IN THE FIELD.
SO THIS IS ONE EXAMPLE OF THE
BIOMECHANICAL DATA THAT WE ARE
COLLECTING.
ANOTHER EXAMPLE IS THAT OF THE
UCSF GROUP THAT IS MAKING USE OF
THE AZURE CONNECT CAMERA CYST
TELL AS WELL AS A CUSTOMIZED
FLOOR MATT WHERE THEY CAN LOOK
AT JOINT MOVEMENTS AS WELL AS
OVERALL POSTURE, AGAIN
VELOCITIES AND ACCELERATIONS,
JOINT FORCES AND MECHANICAL
ENERGY ESTIMATES.
AGAIN, THESE ARE JUST EXAMPLES
OF THE VERY, VERY RICH DATASETS
THAT WE'RE COLLECTING BASED ON
THE BIOMECHANICS.
WE ALSO ARE COLLECTING DATA ON
THE IMAGING, AND THIS IS A GREAT
EXAMPLE OF THE COLLABORATION
BETWEEN SITES.
IN PITTSBURGH, WE ARE COLLECTING
OUR CLINICAL IMAGING AND SENDING
TO UCSF FOR ADVANCED ANALYSIS,
LOOKING AT DIFFERENT COMPONENTS
AND DIFFERENT WAYS WE CAN
ANALYZE THE CLINICAL IMAGES, AND
SEVERAL OF THE SITES ARE ALSO
COLLECTING ADVANCED IMAGES, LIKE
T1 ROW THAT CAN GIVE INFORMATION
ABOUT EARLY DEGENERATIVE CHANGES
IN THE INTERVERTEBRAL DISKS, FOR
EXAMPLE, OR EVEN SPECTROSCOPY,
WHICH SHOWS THE CHEMICAL EXOA
COMPOSITION ACROSS THE
INTERVERTEBRAL DISKS IN A VERY
SENSITIVE FASHION.
WE'RE BIOSAMPLING ALL OF THE
PARTICIPANTS IN THE STUDY WITH
SALIVA, BLOOD, SPINAL TISSUES
FOR THOSE THAT UNDERGO SPINE
SURGERY DURING THE ONE-YEAR
FOLLOW-UP PERIOD, STOOL SAMPLES
AND URINE SO THAT WE CAN LOOK AT
GENOMICS, EP EPIGENOMICS,
MICROBIOME, TRANSCRIPTOMICS,
METABOLOMICS, AND THERE'S BEEN A
LOT OF WORK TO HARMONIZE THE WAY
THAT THE SAMPLES ARE COLLECTED
AT ALL OF THE SITES AS WELL, SO
THAT THE CREATION OF THIS
BIOREPOSITORY CAN BE USED BY
OTHERS.
AND I'LL END BY JUST TELLING YOU
A BIT ABOUT HOW WE'RE STARTING
TO THINK ABOUT PULLING ALL OF
THIS DATA TOGETHER.
AND SO THIS IS AN EXAMPLE THAT
CAROL GRECKO AND HER TEAM, WE
LOOKED AT 10 DIFFERENT FACTORS
OR DOMAINS BASED ON
PATIENT-REPORTED OUTCOMES,
DEMOGRAPHICS AS WELL AS SOCIAL
DETERMINANTS OF HEALTH, AND BY
USING LATENT CLASS ANALYSIS,
WERE ABLE TO IDENTIFY FOUR
DIFFERENT PHENOTYPES OF PATIENTS
FROM THE ENTIRE COHORT.
JUST BASED ON THOSE 10 FACTORS.
IT'S PRETTY ROBUST.
DOING THE SAME THING WITH A
CLUSTER ANALYSIS, A DIFFERENT
MATHEMATICAL APPROACH SHOWS VERY
SIMILAR PATTERNS, THOUGH IT
COLLAPSED INTO THREE DIFFERENT
PHENOTYPES.
SO WE'RE VERY BULLISH ON THIS
AND THINK THAT AS WE START TO
LAYER IN THE BIOMECHANICS AND
THE BIOLOGY ON TOP OF ALL OF THE
PATIENT-REPORTED INFORMATION
THAT WE HAVE THAT WE WILL REALLY
BE ABLE TO TEASE OUT DIFFERENT
TYPES OF PATIENTS AND DIFFERENT
PHENOTYPES OF PATIENTS AND HOW
THEY RESPOND.
SO HOW WE'RE MAKING SENSE OF
THAT SOUP OF DATA, WE HAVE
PREPROCESSED IN PITTSBURGH OVER
600 OF OUR DATA PARTICIPANTS.
WE HAVE PAINSTAKINGLY HAD DATA
RETREATS WHERE WE SIT IN A ROOM
FOR SEVERAL HOURS AT A TIME AND
GO THROUGH ITEM BY ITEM WHAT
FEATURES WE'RE GOING TO PULL OUT
OF EACH DATA COLLECTION.
SO FOR EXAMPLE, ARE WE GOING TO
INCLUDE LEFT HIP RANGE OF MOTION
AND RIGHT HIP RANGE OF MOTION OR
ARE WE GOING TO COME UP WITH
SOMETHING THAT IS GOING TO
HARMONIZE THAT FEATURE?
THEN STARTING TO DO SOME MACHINE
LEARNING.
AGAIN WE'RE VERY EXCITED, THE
EARLY MACHINE LEARNING, YOU CAN
SEE SOME OF THE CORRELATION
COEFFICIENTS HERE AT THE BOTTOM,
BUT LOOKING VERY, VERY GOOD AND
THIS INCLUDES SO FAR JUST THE
PATIENT-REPORTED OUT COME AND
DEMOGRAPHIC DATA, SO AGAIN AS WE
LAYER OTHER THINGS ON, WE THINK
WE'RE GOING TO HAVE A GREAT
ABILITY TO LOOK AT THE
ASSOCIATION WITH PAIN, AS WELL
AS DISABILITY.
AND YOU'LL HEAR MORE ABOUT THAT
AS I PASS TO MY PARTNER.
I'LL JUST END BY THANKING OUR
PITT TEAM.
THIS IS AN AMAZING
MULTIDISCIPLINARY TEAM OF
BIOLOGISTS, CLINICIAN,
ENGINEERS, BIOSTATISTICIAN, ALL
APPROACHING THIS PROBLEM
TOGETHER.
WE HAVE MULTIPLE
CO-INVESTIGATORS INVOLVED IN THE
PROJECT WHO BRING THEIR CONTENT
EXPERTISE TO THE TABLE IN BOTH
DESIGNING AND INTERPRETING THE
DATA, AS WELL AS OUR CHAMPIONS
WHO ARE THE MACHINE THAT MAKE
THE ENGINE RUN ESSENTIALLY.
I'M VERY THANKFUL FOR THE
CONSORTIUM IN GENERAL.
I THINK EVERYONE HAS COME IN TO
BACPAC BY LEAVING THEIR
INDIVIDUAL RESEARCH AGENDAS ONE
TIER BELOW THE OVERARCHING
MISSION OF BACPAC, WHICH HAS
BEEN REALLY, REALLY AMAZING TO
SEE HOW EVERYONE HAS KIND OF
CHECKED THEIR OWN EGOS AT THE
DOOR AND COLLABORATED AND AT
TIMES COMPROMISED TO MAKE SURE
THAT WE ARE DOING SOMETHING THAT
IS WELL REPRESENTING THE PEOPLE
THAT WE ARE LOOKING TO HELP WITH
THE TREATMENTS THAT WE'RE
DESIGNING.
WE'VE LEARNED FROM EACH OTHER,
WE'VE SYNERGIZED, AND TRULY IT'S
BEEN THE GREATEST JOY OF MY
PROFESSIONAL YEAR, AND I REMAIN
HOPEFUL THAT WE'LL KEEP THE BAND
TOGETHER AS WE MOVE FORWARD WITH
THINGS.
SO I'LL PASS IT ON TO ABEL TO
TALK ABOUT HOW WE MAKE SENSE OF
ALL THIS DATA.
>> THAT WAS GREAT.
THANK YOU, GWEN.
I LOVE DATA, SO I'M GOING TO TRY
TO ECK PLAIP EXPLAIN WHAT WE AO
DO AT UCSF TO MAKE SENSE OF ALL
OF THIS DATA.
THE ULTIMATE GOAL IS TO
UNDERSTAND THIS QUESTION THAT WE
HAVE UP HERE ON THE SCREEN, CAN
WE KNOW ALL THE FACTORS THAT
ACTUALLY ARE CAUSING CHRONIC LOW
BACK PAIN?
AND I'M GOING TO START PREMISING
THIS BY THE IDEA THAT MOST CASES
OF CHRONIC PAIN, WE DON'T KNOW
THE EXACT CAUSE, AND IF WE DON'T
KNOW THE CAUSE, WELL, FINDING
THE TREATMENT BECOMES VERY
DIFFICULT.
WE ALL HEARD ABOUT THE TRIAL AND
ERROR THAT GOES INTO DECIDING
WHAT TREATMENT WORKS BEST FOR A
PATIENT.
SO WHY WE DON'T KNOW THE CAUSE?
WELL, THIS IS BECAUSE OF THE
COMPLEXITY OF CHRONIC PAIN.
WE KNOW A LOT OF THE DIFFERENT
FACTORS AND T THAT MAY POTENTIAY
CONTRIBUTE AND INTERACT TO EACH
OTHER TO MAKE THE APPEARANCE OF
PAIN BUT ALSO THE PROGRESSION OF
CROCK PAIN AND THE RESPONSE TO
TREATMENT.
CHRONIC PAIN.
SO TO UNDERSTAND THAT COMPL
COMPLEXITY, GWEN MENTIONED THIS
ALREADY, THE BACPAC CONSORTIUM
DECIDED TO BUILD A THEORETICAL
MODEL, AND SO THEORETICAL
MODELS, YOU HAVE AN EXAMPLE HERE
ON THE SCREEN, IT'S CALLED THE
CONCEPTUAL.
THE EXPERTS HAVE TO DECIDE THESE
ARE THE DIFFERENT FACTORS, HOW
THEY ARE GOING TO INTERACT AND
WHAT ARE THE BASIC MECHANISMS
THAT PAIN SHALL APPEAR, PROGRESS
AND SO ON.
NOW, MODELS ARE A SIMPLIFICATION
OF REALITY.
IT ALLOWS US TO UNDERSTAND
COMPLEX SYSTEMS IN A MUCH MORE,
I GUESS, APPROACHABLE WAY, AND
WE CAN THEN START THINKING OR
SHARE UNDERSTANDING OF WHAT ARE
THE MECHANISMS OF THAT COMPLEX
PHENOMENON, IN THIS PARTICULAR
CASE, PAIN.
NOW WE CAN BUILD MODELS IN
DIFFERENT WAYS.
WE CAN BUILD MODELS FROM DATA
ITSELF, WE CAN BUILD MODELS FROM
THE LITERATURE.
YOU CAN THINK ABOUT A SYSTEMATIC
REVIEW, FOR INSTANCE, STARTING
TO BUILD THAT MODEL.
WE CAN BUILD MODELS FROM ASKING
THE EXPERTS, LAKE THE MODEL THAI
JUST SHOWED.
I'M GOING TO TALK ABOUT THE DATA
MODEL TRYING TO MAKE SENSE OF
ALL THAT.
SO AT UCSF, WE HAVE THE COMEBACK
STUDY, OBSERVATIONAL STUDY, AND
THE GOAL IS DEEP PHENOTYPING AS
GWEN WAS TALKING ABOUT, SO
THERE'S A LOT OF DATA FROM
DIFFERENT DOMAINS THAT ARE
COLLECTING, AND EACH ONE OF THE
COMPLEX SPECIALIZED DATASETS
THAT ARE BEING COLLECTED, THERE
IS A LOT OF WORK THAT GOES INTO
GENERATING EVERYONE'S FAVORITE
VARIABLES.
BUT THE POINT IS, HOW DO WE BIND
ALL THIS INFORMATION SO WE CAN
MAKE SENSE OF IT.
ONE OF THE THINGS WE'RE DOING IS
USING SOME MODELING TECHNIQUES
FROM MACHINE LEARNING WITH THE
IDEA TO BE ABLE TO MAKE SENSE OF
ALL THAT INFORMATION.
SO, SO FAR WE ARE WORKING WITH
679 VARIABLES IN THOSE 450
PATIENTS THAT ARE IN THE
COMEBACK STUDY.
SO THE WAY THAT WE DO THIS IS BY
USING SOME ANALYTICAL PIPELINES
THAT WE CALL MULTIDOMAIN
INTEGRATION, DATA INTEGRATION.
THE IDEA HERE IS TO TEASE APART
THE ACTUAL SIGNALS FROM -- THAT
ARE IMPORTANT FOR THE
PHENOTYPING OF PAIN AND
UNDERSTANDING THE COMPLEXITY OF
PAIN VERSUS WHAT IS NOISE IN ALL
THAT DATA.
WITH THE IDEA THAT WE CAN ANSWER
TWO DIFFERENT QUESTIONS.
THE COMPLEXITY PROBLEM, OR THE
QUESTION OF WHAT ARE THE COMPLEX
RELATIONSHIPS BETWEEN ALL THESE
FACTORS THAT REMIND CHRONIC LOW
BACK PAIN, BUT ALSO A
SUBGROUPING PROBLEM OF WHAT ARE
THE DIFFERENT POTENTIAL
SUBGROUPS OF PATIENTS THAT HAVE
DIFFERENT CHARACTERISTICS OF
THOSE PHENOTYPES.
WE'RE GOING TO BE USING
DIFFERENT TYPES OF MACHINE
LEARNING FOR THIS, BUT WHAT I
WANT TO POINT OUT IS THAT THESE
TWO QUESTIONS ARE RELATED TO
EACH OTHER.
SO THE COMPLEXITY OF THE -- OF
THE POPULATION IS HIGHLY RELATED
TO THE UNDERLYING MECHANISTIC
REASONS FOR WHY PAIN SHOWS UP IN
THOSE POPULATIONS.
SO WHAT YOU HAVE HERE IS AN
EXAMPLE OF -- THAT SUMMARIZES
ONE OF THE MODELS THAT WE HAVE.
SO UNDERNEATH IS A MODEL WITH
679 VARIABLES AND MORE THAN 2000
DIFFERENT RELATIONSHIPS.
AND SO THIS ILLUSTRATES THAT
COMPLEXITY, AND WHAT YOU HAVE IS
THE NAME OF THE DIFFERENT
DOMAINS OF DATA THAT GWEN WAS
TALKING ABOUT, AND ALL THE
VARIABLES, HOW DO THEY RELATE TO
EACH OTHER.
SO TO GIVE YOU AN EXAMPLE, THIS
IS A VERY COMPLEX MODEL BUT WE
VIEW AN EXAMPLE OF HOW THAT
LOOKS LIKE, WE CAN TAKE A LOOK
AT THESE THREE DIFFERENT
DOMAINS: PAIN CHARACTERISTICS,
SYMPTOMS, AND THOUGHTS AND
BELIEFS.
AND BASICALLY, UNDERNEATH THIS
MODEL IS A NETWORK.
AND THESE NETWORKS ARE BASICALLY
RELATIONSHIPS BETWEEN THE
DIFFERENT FACTORS THAT ARE THE
VARIABLES THAT YOU HAVE THERE IN
THE DOTS, AND THE ARROWS POINTS
OUT WHAT ARE THE CAUSAL
RELATIONSHIPS BETWEEN ALL OF
THOSE.
NOW WE CAN DO A LOT OF THINGS
WITH THESE MODELS BUT ONE I'M
VERY FOND OF IS THAT WE CAN
START SIMULATING HYPOTHESIS
ABOUT THE COMPLEXITY AND
BEHAVIOR OF CHRONIC PAIN.
SO FOR INSTANCE, WE CAN DO A
SIMULATION AND SAY, WHAT WILL
HAPPEN IF WE TREAT PEOPLE FOR
ANXIETY IN THIS POPULATION?
AND WHAT HAPPENED IS THAT ALL
THAT INFORMATION POPULATES IN
THE NETWORK SO WE CAN TRY TO
UNDERSTAND AND GENERATE A NEW
HYPOTHESIS THAT CAN BE BROUGHT
INTO CLINICAL TRIALS.
SO THAT'S WHEN IT COMES TO THE
COMPLEXITY PROBLEM, PHENOTYPING
WITHOUT GETTING MUCH INTO THE
DETAIL OF THE SUBGROUPING, WE'VE
DONE SOME PIPELINES ON THESE AND
YOU HAVE HERE A REPRESENTATION
OF SIX DIFFERENT GROUPS.
SO WE CAN TAKE A LOOK AT WHAT
THEY ARE BASED ON THEIR CLINICAL
CHARACTERISTICS.
FOR INSTANCE, THAT GROUP UP
THERE WOULD HAVE MOSTLY FEMALES,
COMORBIDITIES, PAIN INTENSITY,
PAIN INTERFERES, IN COMPARISON
TO THIS GROUP DOWN HERE THAT
HAVE COMORBIDITIES YOUNG AND
HIGH LEVELS OF ANXIETY.
WE CAN ALSO LOOK AT THE NETWORKS
THAT CAPTURE THE MECHANISTICS OF
THESE PATIENTS SO WE CAN START
UNDERSTANDING WHAT ARE THE
CAUSAL MECHANISMS OF THE
APPEARANCE OR WHAT MAKES THESE
PATIENTS DIFFERENT.
SO WE'RE STILL WORKING ON THIS
BECAUSE WE CAN ALSO THEN START
COMPARING ALL THESE NETWORKS
ACROSS THE DIFFERENT CLUSTERS.
SO I'LL LEAVE YOU WITH SOMETHING
WE'RE TRYING TO THINK ABOUT,
BECAUSE WHEN WE TALK ABOUT
MODELING, ONE OF THE PROBLEMS IS
THAT MODELING FROM DATA, OR
MODELING FROM THE EXPERT
LITERATURE BRINGS UP CHALLENGES
AND THEIR BIASES FOR EACH ONE OF
THESE TYPES OF MODELS.
SO THE QUESTION OF WHAT IS
TRUTH, ON ALL THIS, WE TEND TO
THINK ABOUT HAVING DIFFERENT
MODELS THAT COMES FROM THESE
DIFFERENT PERSPECTIVES, AND THEY
CAN SHARE INFORMATION, WITH THE
IDEA THAT THE MODELS FROM THE
DATA GIVES US WHAT ARE THE
PATTERNS THAT WE CAN SEE AND THE
MODELS FROM THE LITERATURE AND
EXPERTS GIVES US THE MECHANISTIC
UNDERSTANDING WITH THE GOAL THAT
THEN WE CAN BUILD A MODEL THAT
IS REAL, BUT ALSO CAPTURED THOSE
MECHANISMS, THEN WE COULD PUT
THAT MODEL TO ACTION, DO SOME OF
THOSE SIMULATIONS, AND SO ON.
SO I'M GOING TO LEAVE THIS HERE
AND THIS IS WORK WE'VE BEEN
DOING AT UCSF WITH THE REACH
TEAM.
THANK YOU.
>> GOOD MORNING, EVERYONE.
MY NAME IS MATT MAUCK FROM THE
UNIVERSITY OF NORTH CAROLINA.
I'M HERE TO TALK TO YOU TODAY
ABOUT THE BIOMARKERS FOR
EVALUATING SPINE TREATMENTS
TRIAL.
THAT GWEN INTRODUCED.
THE GOAL WITH THIS TRIAL IS TO
DEVELOP A PRECISION MEDICINE
ALGORITHM TO HELP ASSIGN THE
BEST SEQUENCE OF TREATMENTS FOR
INDIVIDUALS WITH CHRONIC LOW
BACK PAIN.
WE ALSO HOPE TO DISCOVER
BIOMARKERS THAT PREDICT
TREATMENT RESPONSE AND
CONTRIBUTE TO OUR UNDERSTANDING
OF THE PATHOGENESIS OF CHRONIC
LOW BACK PAIN.
WE'VE SUCCESSFULLY RECRUITED OUR
COHORT INTO THE STUDY, AND HAVE
RECRUITED OVER A THOUSAND
PATIENTS INTO BEST.
THERE ARE SEVERAL INTERVENTIONS
THAT WE KNOW HELP PATIENTS WITH
LOW BACK PAIN.
THESE ARE LISTED HERE AND ARE
THE INTERVENTIONS THAT WE'RE
USING IN THE BEST TRIAL.
FOR EXAMPLE, DULOXETINE MIGHT
WORK REALLY WELL FOR SOME
PATIENTS BUT NOT FOR OTHERS.
THAT'S WHY WE DEVELOPED THE BEST
TRIAL AS A CONSORTIUM TO HELP US
UNDERSTAND AND DISENTANGLE WHY
SOME PATIENT RESPOND AND OTHERS
DON'T.
THE BIOMARKERS FOR EVALUATING
SPINE TREATMENTS TRIAL, WE CALL
IT THE BEST TRIAL, AND IT'S THE
COLLABORATIVE CENTERPIECE OF THE
BACK PAIN CONSORTIUM.
WE ALL CAME TOGETHER AS A TEAM
AND DEVELOPED THE PROTOCOL AND
THE ALGORITHM AND THE
PHENOTYPING THAT WE'RE
DEVELOPING IN THIS TRIAL.
WE SETTLED ON AN ADAKTIVE
DESIGN, A SMART TRIAL DESIGN.
THIS IS ONE OF THE LARGEST
SMARTS TO BE PERFORMED IN
MEDICINE.
IT'S ALIGNED WITH -- WE HAVE TWO
3-MONTH TREATMENT PERIODS VERY
MUCH ALIGNED WITH PATIENTS IN
THE CLINICAL SETTING.
WE USE A BROAD INCLUSION
CRITERIA.
THE GOAL IS TO MAKE THE RESULTS
MOST GENERALIZABLE TO THE U.S.
POPULATION THAT EXPERIENCES
CHRONIC LOW BACK PAIN.
WE ENROLLED THESE PARTICIPANTS
ACROSS 12 CLINICAL SITES.
THESE SITES ARE OUT STANDING,
AND REALLY WORK TOGETHER TO
ACCOMPLISH THE ENROLLMENT WITH
THE LEADERSHIP FROM THE DAK,
WHICH YOU'LL HEAR ABOUT A LITTLE
BIT LATER.
WHAT MAKES BEST INNOVATIVE AND
UNIQUE IS THE RICH MULTIMODAL
PHENOTYPING THAT WE'RE
PERFORMING IN THE BEST TRIAL.
WE'RE COLLECTING INFORMATION ON
PATIENT-REPORTED MEASURES,
BIOMECHANICS AND ACTIVITY,
BIOLOGICAL MARKERS, AND GWEN
MENTIONED FROM THE STOOL AND
FROM BLOOD.
WE'RE ALSO COLLECTING BIOMEDICAL
IMAGING, WE'RE COLLECTING
FUNCTIONAL NEUROIMAGING AS WELL
AS BASELINE CLINICAL SPINE
MRIs AT THE BASELINE, WHICH
I'LL TELL YOU ABOUT IN A MOMENT.
TO BUILD OFF OF WHAT ABEL WAS
DISCUSSING, PATIENTS WITH
CHRONIC LOW BACK PAIN ARE VERY
COMPLEX.
THESE REPRESENT THREE PROFILES
OF PATIENTS THAT I WAS ABLE TO
TAKE CARE OF AT BASELINE IN THE
BEST TRIAL.
DR. MARRAS' GROUP AT THE OHIO
STATE SPINE RESEARCH INSTITUTE
PUT THIS TOGETHER FOR US.
ON THE TOP ROW ARE SOME DETAILS
ABOUT THESE INDIVIDUALS'
BIOMECHANICS.
DOWN BELOW DESCRIBE THE
INDIVIDUALS' PAIN EXPERIENCE,
DESCRIBES THE LOCATIONS WHERE
THEY'RE HAVING PAIN, AS WELL AS
THE PROMIS MEASURES THAT
REPRESENT ANXIETY, DEPRESSION,
FATIGUE.
YOU CAN SEE THAT EACH OF THESE
PATIENTS ARE VERY UNIQUE, BUT
LIKELY FIT SOMEWHERE WITHIN
THESE CLUSTERS THAT ABEL
DESCRIBED IN HIS TALK, AND
CHECKING THESE PHENOTYPING
MEASURES WILL HELP US PLACE
THESE INDIVIDUALS WITHIN THESE
CLUSTERS, AND HOPEFULLY WILL
LEARN ABOUT WHAT IS CAUSATIVE
AND WHAT CAUSES CHRONIC LOW BACK
PAIN AS PART OF DOING THIS
TRIAL.
I'D LIKE TO TAKE YOU ON A TOUR
OF THE BEST TRIAL BY DISCUSSING
TWO PATIENTS THAT I WAS ABLE TO
TAKE CARE OF THROUGH THIS TRIAL.
THE FIRST ON THE LEFT IS A
67-YEAR-OLD FEMALE WITH A
20-YEAR HISTORY OF CHRONIC LOW
BACK PAIN.
YOU CAN SEE THIS INDIVIDUAL ON
THE MICHIGAN BODY MAP, THE AREAS
IN BLUE DENOTE AREAS WHERE THE
INDIVIDUAL IS HAVING PAIN, AS
PRIMARILY AXIAL LOW BACK PAIN.
ALL THE PATIENTS IN THE BEST
TRIAL HAD PREDOMINANTLY LOW BACK
PAIN.
AND THIS PATIENT PRIMARILY HAD
AXIAL LOW BACK PAIN WITH A FEW
EXTRA AXIAL SITES OF PAIN YOU
CAN SEE IN THE RIGHT KNEE AND
WRIST.
THAT'S IN CONTRAST TO THE
PATIENT ON THE RIGHT, WHO'S A
41-YEAR-OLD MALE WITH A 10-YEAR
HISTORY OF CHRONIC LOW BACK
PAIN, AND THIS INDIVIDUAL HAS
MORE WIDESPREAD FEATURES OF
PAIN, EXPERIENCES CHRONIC LOW
BACK PAIN AS THE MAJORITY OF
THIS INDIVIDUAL'S PAIN, BUT ALSO
HAS OTHER EXTRA AXIAL SITES OF
PAIN, MUCH GREATER THAN THE
PATIENT ON THE LEFT.
I WANTED TO SHOWCASE AN EXAMPLE
OF SOME OF THE BIOMARKERS THAT
WE'RE COLLECTING IN THE BEST
TRIAL.
THIS IS AN EXAMPLE BIOMECHANICAL
MEASURE THAT WAS COLLECTED BY
THE OHIO STATE UNIVERSITY ACROSS
ALL OF THE CENTERS THAT
PARTICIPATED IN THIS.
AND THIS SHOWS THE BIOMECHANICAL
ASSESSMENT FOR THESE TWO
PATIENTS.
I'VE SHOWN YOU A COMPOSITE
MEASURE ON THE BOTTOM
DEMONSTRATING THE OVERALL LOW
BACK PAIN MOTION LISTED AS AN
INDEX.
YOU CAN SEE THE PATIENT ON THE
LEFT HAD MUCH HIGHER RANGE OF
MOTION, VELOCITY, ACCELERATION
IN ALL PLANES COMPARED TO THE
PATIENT ON THE RIGHT.
DR. MARRAS' TEAM HAS PUT
TOGETHER A VIDEO THAT SHOWS US
THE INDIVIDUAL SPINE MOTION
BETWEEN THESE TWO INDIVIDUALS TO
A LATERAL BENDING TASK WHERE HE
ASKS PARTICIPANTS TO MOVE SIDE
TO SIDE AS FAST AS THEY CAN.
AND DR. MARRAS' TEAM WAS ABLE TO
USE THE CLINICAL SPINE IMAGING
TO MAP A THREE-DIMENSIONAL MODEL
AND PLOT, DATA THAT WAS
COLLECTED BY SENSORS THAT WERE
PLACED ON INDIVIDUALS WHILE
DOING THIS TASK ON TO THESE
CLINICAL SPINES, AND THEN NOW
MADE A VIDEO SHOWING YOU THEIR
MOTION.
HOPEFULLY WE CAN PLAY THE VIDEO.
WELL, SUFFICE IT TO SAY, THE
SPINE ON THE LEFT MOVES A LOT
WITH A LOT GREATER ACCELERATION.
IF YOU CAN PLAY IT, THAT WOULD
BE GREAT.
THANKS.
SO YOU CAN SEE THE PATIENT ON
THE LEFT HAS MUCH GREATER SPINE
MOTION THAN THE PATIENT ON THE
RIGHT.
HAS GREATER RANGE OF MOTION,
VELOCITY, AND ACCELERATION.
I THINK THIS GIVES YOU A
SNAPSHOT ABOUT HOW DIFFERENT
PATIENTS ARE THAT PRESENT WITH
CHRONIC LOW BACK PAIN, AND ALSO
GIVES US AS CLINICIANS USEFUL
BIOMARKERS THAT MIGHT PREDICT
TREATMENT RESPONSE.
THE FISHES PATI FIRST PATIENT I,
THE FEMALE PATIENT, RECEIVED T
THE -- THIS INDIVIDUAL WAS
RANDOMIZED TO EVIDENCE-BASED
EXERCISE AND MANUAL THERAPY,
WHICH IS OUR ENHANCED PHYSICAL
THERAPY TREATMENT.
THE OTHER PATIENT, THE
41-YEAR-OLD MALE, WAS ASSIGNED
TO ENHANCE SELF-CARE, WHICH IS A
SELF-DIRECTED DIGITALLY
DELIVERED BIOBEHAVIORAL
MANAGEMENT TREATMENT THAT
INVOLVED A WALKING PROGRAM, AS
WELL AS GUIDANCE ON OVER THE
COUNTER MEDICATIONS.
SO THESE INDIVIDUALS UNDERWENT
12 ADDITIONAL WEEKS OF TREATMENT
AND THEN RE-PRESENTED TO CLINIC
FOR ADDITIONAL PHENOTYPING AS
WELL AS RANDOMIZATION TO A
SECOND INTERVENTION.
WE RANDOMIZED PATIENTS TO THE
SECOND INTERVENTION BASED ON
THEIR RESPONSE TO THE FIRST
INTERVENTION.
PATIENTS THAT DID VERY WELL WERE
MAINTAINED ON THE FIRST STAGE
INTERVENTION FOR THE SECOND
STAGE.
INDIVIDUALS THAT HAD A MODERATE
RESPONSE WERE AUGMENTED WITH AN
ADDITIONAL TREATMENT FOR THE
SECOND STAGE AND CONTINUED THE
FIRST STAGE OF TREATMENT.
YOU FINALLY, INDIVIDUALS THAT DT
RESPOND AT ALL WERE RANDOMIZED
TO A NEW INTERVENTION FOR THE
SECOND TREATMENT PERIOD.
IN ADDITION TO CONTINUING THE
FIRST INTERVENTION THEY WERE
ASSIGNED.
THIS IS A 67-YEAR-OLD FEMALE
THAT WE DISCUSSED.
THIS INDIVIDUAL WAS ASSIGNED TO
PHYSICAL THERAPY FOR THE FIRST
INTERVENTION, WENT THROUGH THAT
INTERVENTION, AND HAD A MODERATE
RESPONSE.
WAS THEN AUGMENTED WITH ENHANCED
SELF-CARE AND RANDOMIZED
ENHANCED SELF-CARE FOR THE
SECOND 12-WEEK PERIOD AND WHEN
THEY CAME BACK TO CLINIC, HAD A
REALLY REMARKABLE CLINICAL
RESPONSE.
IT'S POSSIBLE THAT THIS
INDIVIDUAL RECEIVED THE BEST
SEQUENCE OF TREATMENTS TO TREAT
THEIR LOW BACK PAIN.
THE QUESTION WE HOPE TO ANSWER
WITH THE DATA WE'RE COLLECTING
IN THE BEST TRIAL IS WHAT
BIOMARKERS WOULD HAVE PREDICTED
THAT AND COULD WE REPRODUCIBLY
ASSIGN INTERVENTIONS BASED ON
THOSE BIOMARKERS.
THE SECOND PATIENT I DISCUSSED
RECEIVED THE ENHANCED SELF-CARE
FOR THE TREATMENT PERIOD WAS
AUGMENTED WITH PHYSICAL THERAPY
FOR THE SECOND STAGE TREATMENT.
THIS INDIVIDUAL DIDN'T RESPOND
SO WELL TO THE ENHANCED
SELF-CARE.
BUT HAD A ROBUST RESPONSE TO
PHYSICAL THERAPY.
IN THIS CASE, THE QUESTION
BECOMES, IF WE WOULD HAVE
ASSIGNED PHYSICAL THERAPY TO
THIS INDIVIDUAL FIRST, WOULD
THEY HAVE HAD THAT GREAT
RESPONSE RIGHT AWAY?
AND ARE THERE BIOMARKERS THAT
WOULD HAVE PREDICTED THAT?
I WANTED TO SHARE THESE CASES TO
GIVE YOU A FLAVOR OF HOPEFULLY
WHAT WE'RE ABLE TO DO WITH THE
DATA WE COLLECT FROM THE BEST
TRIAL, AND OUR VISION IS THAT
WE'LL BE ABLE TO GIVE PHYSICIANS
AND CLINICIANS AT THE BEDSIDE A
PRECISION ALGORITHM THAT WILL
GUIDE THEIR TREATMENT.
THANKS.
>> THANK YOU.
I'M KEVIN ANSTROM.
I WORK AT UNIVERSITY OF NORTH
CAROLINA WITH MATT, AND I'M PART
OF A LARGER GROUP CALLED THE DAC
THAT WE'LL DISCUSS A LITTLE BIT
LATER.
SO THERE ARE REALLY TWO THINGS
THAT I'LL BE PRESENTING HERE.
ONE IS AROUND A TOOL THAT WE'VE
DEVELOPED OR A SET OF TOOLS, THE
BACPAC DATA PORTAL, AND THEN THE
SECOND WILL BE JUST A VERY BRIEF
UPDATE OF WHERE WE STAND ON THE
BEST TRIAL THAT GWEN AND MATT IT
HAD OUTLINED EARLIER.
SO IN TERMS OF DATA SHARING,
DATA WORKING GROUP, THERE'S A
COMMITTEE THAT PUT TOGETHER A
SET OF PROCESSES OR PLANS.
ADDITIONALLY, WE HAVE A DATA
PORTAL THAT'S BEEN PUT TOGETHER,
AND WHAT YOU SEE FROM THIS
SCWEEM HERE IS EACH OF THE
RESEARCH SITES, AND AGAIN, THERE
ARE MANY SITES, THEY INTERACT
WITH A TEAM AT THE DAC, AND
ESSENTIALLY GOING BACK AND FORTH
TO MAKE SURE THAT THE DATA
STANDARDS ARE MET.
AGAIN, THOSE WOULD BE THE HEAL
DATA STANDARDS AS WELL AS THE
BACPAC DATA STANDARDS, AND THEN
THE DATA IS STORED IN A
COMMONPLACE.
THE BOTTOM PART OF THE FIGURE
HERE WOULD BE AN INDIVIDUAL
RESEARCHER THAT WOULD BE
INTERESTED IN ACCESSING THOSE
POOLED RESOURCES FROM ACROSS THE
STUDY, AND THEY BASICALLY WOULD
HAVE TO GAIN AUTHORIZATION TO
USE THE SYSTEM ONCE THEY HAD
AUTHORIZATION AND HAD THE RIGHT
APPROVAL, THEY WOULD GO IN AND
ESSENTIALLY LOG IN TO THE
SYSTEM.
THIS GOES THROUGH SOME OF THE
STEPS THAT ARE REQUIRED BEFORE
DOING THE TRANSFERS, AND AGAIN,
THIS IS A PROCESS THAT OBVIOUSLY
REQUIRES THE CORRECT
PERMISSIONS, ET CETERA.
THIS IS ANOTHER SCHEME, WE DON'T
HAVE TIME TO GO THROUGH THE
DETAILS, BUT ESSENTIALLY
EVERYONE THAT WOULD GET
PERMISSION WOULD HAVE THE PROPER
AUTHORITIES, ET CETERA.
AND HERE JUST MAYBE A COUPLE
SCREEN SHOTS OF WHAT IT WOULD
ACTUALLY LOOK LIKE FOR THE
SYSTEM ITSELF.
AND THEN AT THE SORT OF END OF
THE PROJECTS, WE'LL BE COMPLYING
WITH OTHER HEAL REQUIREMENTS.
WE WILL LIKELY USE MORE THAN A
SINGLE REPOSITORY, AND WE CAN GO
INTO DETAILS IF PEOPLE HAVE
QUESTIONS LATER.
NOW QUICKLY JUMPING TO WHAT HAD
BEEN DESCRIBED EARLIER, THE BEST
TRIAL, AGAIN, THE BEST TRIAL IS
ONE OF THE CENTER PIECES OF THE
OVERALL BACPAC WORK.
IT'S A LARGE PRECISION MEDICINE
DESIGN STUDY, AND AGAIN, THERE'S
TWO TREATMENT PERIODS.
EACH OF THOSE WOULD BE THREE
MONTHS LONG.
IT'S A TYPE OF STUDY THAT
STATISTICIANS AND OTHERS CALL
THIS A SMART SEQUENTIAL MULTIPLE
ASSIGNMENT RANDOMIZED TRIAL.
AGAIN, WE START WITH FOUR
INDIVIDUAL INTERVENTIONS, AND
OBVIOUSLY WE COLLECT A
TREMENDOUS AMOUNT OF
INFORMATION.
THERE'S A SUBSET, WE COLLECT A
LOT OF INFORMATION, AND THEN A
SUBSET WE COLLECT EVEN MORE,
THAT WOULD BE THE DEEP PHENOTYPE
SUBSET.
JUST IN TERMS OF PRECISION
MEDICINE FOR DEFINITION,
ESSENTIALLY IT'S SOME VERSION OF
GETTING THE RIGHT TREATMENT FOR
THE RIGHT PERSON AT THE RIGHT
TIME.
AND ESSENTIALLY IT'S CALLED LOTS
OF DIFFERENT THINGS IN THE
LITERATURE, IN THE STATISTICAL
LITERATURE IT'S OFTEN CALLED
DYNAMIC TREATMENT JE REGIME.
WE'LL JUST GO THROUGH A COUPLE
LITTLE EXAMPLES HERE.
SO THIS IS SORT AFTER VERY
COMMON SCHEMA THAT WOULD BE
USED, AND JUST IN GENERAL HERE,
WE COULD DO THINGS LIKE COUNT
THE NUMBER OF EMBEDDED TREATMENT
REGIMES.
SO HERE IT'S A CASE WHERE THE
Rs STAND FOR POINTS OF
RANDOMIZATION, AND THE B, C, D
AND E, THOSE STAND FOR DIFFERENT
INTERVENTIONS.
AND SO IN THIS CASE, YOU SEE
SORT OF AS YOU MOVE FROM LEFT TO
RIGHT OVER TIME, A PARTICULAR
INDIVIDUAL WOULD BE RANDOMIZED
AT TWO TIME POINTS.
HERE THERE WOULD BE ESSENTIALLY
FOUR EMBEDDED TREATMENT REGIMES.
YOU WOULD HAVE B TO D, THAT
WOULD BE ONE.
YOU WOULD HAVE B TO E, THAT
WOULD BE TWO.
C TO D, THREE.
AND THEN C TO E, FOUR.
SO AGAIN, THAT'S A SIMPLE
STRUCTURE WHERE THERE ARE SORT
OF NO TAILORING VARIABLES.
HERE'S A SITUATION THAT'S
SLIGHTLY MORE COMPLICATED BUT IT
TURNS OUT IN THIS SETTING THERE
ARE ONLY THREE EMBEDDED
TREATMENT REGIMES.
PROBABLY THE EASIEST TO TAKE
CARE OF IS THE ONE ON THE BOTTOM
WHERE A PERSON WOULD START ON C
AND IF THEY RESPONDED AT KIND OF
THE INTERMEDIATE TIME POINT,
THEY WOULD CONTINUE ON C, OR
THEY WOULD START ON C IF THEY
DID NOT RESPOND, THEY WOULD GO
TO C PLUS SOMETHING LIKE AN
AUGMENTATION.
THAT WOULD BE SORT OF ONE OF
THESE EMBEDDED TREATMENT
REGIMES.
ON THE TOP, IT TURNS OUT THERE'S
ACTUALLY TWO DIFFERENT EMBEDDED
TREATMENT REGIMES.
A PERSON COULD START WITH B AND
IF THEY RESPOND THEY CONTINUE ON
B, OR IF THEY DIDN'T RESPOND,
THEY COULD GO TO B WITH SOME
SORT OF AUGMENTATION, THAT WOULD
BE THE SECOND OF THESE EMBEDDED
TREATMENT REGIMES.
THE-1/3 WOULD BE ESSENTIALLY THE
CASE WHERE A PERSON STARTS WITH
B, THEY DO NOT RESPOND AND THEN
YOU WOULD ESSENTIALLY AUGMENT
THEM WITH C, SO THEY'D END UP
WITH B PLUS C.
SO AGAIN THAT'S THE SORT OF
SETUP WE'RE DOING FOR THIS
COMPLICATED STUDY.
I WON'T SPEND TIME GOING THROUGH
THE NUMBER OF EMBEDDED TREATMENT
REGIMES HERE.
MY DAUGHTER SAID IT'S ROUGHLY
THE NUMBER OF TIMES WE EXPECT TO
SEE TAYLOR SWIFT MENTIONED AT
THE SUPER BOWL.
THAT'S PROBABLY NOT QUITE RIGHT.
BUT JUST SORT OF A FUN FACT, A
TYPICAL PROFESSIONAL FOOTBALL
GAME, NFL GAME, THERE ARE ABOUT
153 PLAYS PER GAME, SO 153.
THE NUMBER OF EMBEDDED TREATMENT
REGIMES IS ABOUT ROUGHLY THAT
NUMBER.
IN ADDITION, YOU THINK OF WHAT
ABEL SHOWED EARLIER IN TERMS OF
THE PHENOTYPIC DATA THAT WE'RE
CAPTURING.
THIS ENDS UP BEING A VERY
COMPLICATED PROCESS.
IN ADDITION TO THAT, THIS IS
SORT OF HITTING ON SOME OF THE
OBJECTIVES EARLIER.
SO AGAIN, THIS IS A PRECISION
MEDICINE -- THAT WILL BE
DEVELOPED AND THE FORMAL
OBJECTIVE HERE IS WE'RE TAKING
THESE SORT OF TWO DIFFERENT
SEQUENCES, WE HAVE THE DIFFERENT
INTERVENTIONS AND WE'RE GOING TO
USE THE BIOMARKER INFORMATION TO
IMPROVE THAT.
SEEMS TO HAVE ITS OWN MIND HERE.
SO -- TIMELINES, AWESOME.
SO WHERE WE ARE IN TERM OF TIME
LINES -- I SWEAR I'M NOT DOING
THIS.
MATT MENTIONED WE'D COMPLETED
SCREENING AND ENROLLMENT WITH
JUST OVER A THOUSAND
PARTICIPANTS.
IN TERMS OF RANDOMIZATION, AGAIN
THERE WAS A RUN-IN PERIOD AND A
FEW OTHER THINGS.
IN TERMS OF RANDOMIZATION, WE
HAVE SLIGHTLY OVER 800 PEOPLE
RANDOMIZED TO THE FIRST OF THESE
INDIVIDUAL TREATMENTS.
WE ANTICIPATE -- WE ANTICIPATE
HAVING TWO DESIGN PAPERS
SUBMITTED OVER THE NEXT MONTH OR
SO, ONE FOCUSED ON CLINICAL
ISSUES, HOW THE INDIVIDUAL
INTERVENTIONS WERE SELECTED, ET
CETERA.
ONE DEALS WITH SOME OF THE
STATISTICAL ISSUES AROUND
RANDOMIZATION BALANCING, ET
CETERA.
IN TERMS OF THE PARTICIPANTS IN
THE STUDY, THE FINAL STUDY
VISITS WILL HAPPEN LATER IN
2024.
DATABASE LOCK IS ANTICIPATED TO
BE LATE THIS CALENDAR YEAR.
AND IN TERMS OF THE TEAM, AGAIN,
THIS IS PART OF THE DAC AS WELL
AS THE OVERALL BACPAC TEAM, AND
AGAIN, THIS IS A PHOTOGRAPH THAT
WAS TAKEN FROM -- I THINK IT WAS
SPRING OF LAST YEAR.
AND AGAIN, THIS IS MANY OF THE
PEOPLE PART OF THE PROJECT,
AGAIN, THERE ARE MORE.
THAT'S ALL WE HAVE TO PRESENT
TODAY, AND AGAIN, THANK YOU FOR
HAVING US.
>> I'M KATHLEEN SLOKA,
UNIVERSITY OF IOWA.
YOU HAVE A LOT OF BIOMARKERS
WHICH IS GREAT.
I DIDN'T GATHER -- YOU'RE
LOOKING AT THEM CLEARLY PRIOR TO
RANDOMIZATION AND TREATMENT.
ARE YOU LOOKING AT THEM AT EACH
TIME PERIOD AS WELL TO SEE IF
THERE ARE CHANGES IN THOSE AND
THEN TO ME, THAT GETS AT WHETHER
OR NOT THAT'S IMPORTANT IN TERMS
OF MECHANISM OR IS IT JUST
SOMETHING THAT HELPS US PREDICT?
IF YOU UNDERSTAND WHAT I'M
SAYING.
>> I THINK IT'S A GREAT
QUESTION, AND SOMETHING WE'VE
WRESTLED A LOT WITH.
AND THE ANSWER IS REALLY BOTH.
SO JUST TO SEPARATE THIS OUT A
LITTLE BIT, SOME OF THIS IS
OBSERVATIONAL, SO TWO OF THE
THREE MECHANISTIC RESEARCH
CENTERS ARE COLLECTING
OBSERVATIONAL DATA AND FOLLOWING
PATIENTS LONGITUDINALLY, AND
THEN THERE'S THE CLINICAL TRIAL
DOING DEEP PHENOTYPING AT
MICHIGAN AS WELL AS THE BEST
TRIAL.
EACH OF THOSE HAVE TOUCH POINTS
THROUGHOUT THE CONTINUUM.
THE ENTIRETY OF THE DEEP
PHENOTYPING IS NOT OCCURRING AT
EVERY TIME POINT BUT MUCH OF IT
IS REPEATED.
SO IN PARTICULAR, THE
PATIENT-REPORTED OUTCOMES ARE
COLLECTED LONGITUDINALLY IN ALL
OF THEM.
ELECTRONIC MEDICAL RECORD DATA
COLLECTED LONGITUDINALLY IN ALL
OF THEM.
WE HAVE BIOSAMPLING AT DIFFERENT
POINTS IN THE BEST TRIAL, WE
ALSO HAVE IMAGING TIME POINTS AT
MULTIPLE POINTS WITHIN THE BEST
TRIAL.
NOT IN THE OBSERVATIONAL TRIAL.
SO THERE'S A LITTLE BIT OF BOTH
TRYING TO USE THE DATA AS
PREDICTIVE TOOLS AND THEN USE
THE DATA AS MECHANISTIC
INFORMATION OF WHO IS RESPONDING
AND HOW DID THINGS CHANGE.
AS WE TALK ABOUT THIS AMONGST
THE CONSORTIUM, AND I WELCOME
OTHERS TO CHIME IN HERE, THE WAY
WE'RE THINKING ABOUT IT IS,
WE'RE REALLY DEVELOPING THOSE
NOVEL MECHANISTIC THINGS WE NEED
TO STUDY GOING FORWARD.
>> ARE YOU STORING THE TISSUE IN
THE SAMPLES FOR FUTURE ANALYSES
BUT YOU'RE NOT ACTUALLY
COLLECTING THE PROTEOMICS
METABOLOMICS?
>> OH, NO, WE'RE DOING MA SICK E
OMICS AND ADDITIONALLY --
>> I MISSED THAT, I DIDN'T KNOW
YOU HAD THE WHOLE GROUPS DOING
IT.
THAT'S WONDERFUL.
THANK YOU.
>> SO, HI, LINDSAY CRISWELL,
DIRECTOR OF NIAMS.
I DIDN'T WANT TO MISS THIS VERY
PUBLIC OPPORTUNITY TO EXPRESS
THE SUPPORT AND ENTHUSIASM FOR
THIS PROGRAM ON BEHALF OF MY
COLLEAGUES.
EVERYTHING FROM THE EXTENT TO
WHICH YOU'RE PRACTICING PATIENT
ENGAGEMENT, THE EFFORTS DIRECTED
AT DATA HARMONIZATION, THE
THEORETICAL MODEL THAT YOU
DEVELOPED THAT'S REALLY
INSPIRING US TO THINK ABOUT THAT
ACROSS HEAL AND IN OTHER
PROGRAMS, AND SOMETHING THAT YOU
DIDN'T MENTION, WHICH WERE THE
OBSTACLES THAT YOU OVERCAME
RELATED TO THE FACT THAT THE
BEST TRIAL RECRUITMENT OVERLAPS
OVERLAPPED SOME WITH THE COVID
PANDEMIC AND YOU EXCEEDED YOUR
ENROLLMENT.
THAT REALLY SPEAKS TO YOUR
COMMITMENT HERE.
LASTLY, SOMETHING ELSE THAT
DIDN'T COME OUT IN THIS SESSION
BUT WE'RE REALLY EXCITED TO SEE
THE EXTENT TO WHICH THE BACPAC
PROGRAM IS ALSO BEGINNING TO
HAVE CROSSTALK AND COLLABORATION
WITH SOME OF THE OTHER PROGRAMS
ACROSS HEAL REJOIN PRECISION
MYOFASCIAL PAIN, SO WE'RE REALLY
EXCITED ABOUT HOW WE CAN BUILD
UPON YOUR CONTRIBUTIONS TOWARDS
A MUCH GREATER UNDERSTANDING OF
THIS COMPLEX PROBLEM.
SO THANK YOU SO MUCH FOR YOUR
HARD WORK AND DEDICATION. 3236 01:45:12,472 >> THANK YOU.