SO NOW TO GET THINGS STARTED FOR
THE DAY I WANT TO WELCOME TWO
CO-CHAIRS BOTH OF WHOM YOU HEARD
FROM YESTERDAY, DR. BOB OWENS
AND THIS WILL BE FOLLOWED BY THE
FRAMING OF TODAY'S SESSION WITH
THE PRESENTATION ENTITLED
HETEROGENEITY AND OHS RESPONSE
AND ITS IMPLEMENTATION.
DR. OWENS, WHEN YOU'RE READY FOR
THE SUMMARY, PLEASE TAKE IT
AWAY.
>> THANKS, ALFONSO.
CAN YOU SEE MY SLIDES?
>> LOOKS GOOD.
>> PERFECT.
OKAY.
SO GOOD MORNING OR GOOD
AFTERNOON DEPENDING ON YOUR
LOCATION AROUND THE WORLD.
THANK YOU SO MUCH FOR JOINING US
ON DAY TWO.
MY JOB IS TO TRY TO SUMMARIZE
DAY ONE IN FIVE MINUTES WHICH IS
AS CHALLENGES AS IT SOUNDS.
THANK YOU TO ALL OUR SPEAKERS
YESTERDAY.
I'M HOPING TO VERY BRIEFLY
HIGHLIGHT ONE POINT OR SLIDE
FROM EACH SPEAKER.
I THINK THE THEME WAS
INFORMATION OVERLOAD BUT I WANT
TO START WITH THE TALK YESTERDAY
REALLY FOCUSING ON WHAT WE DON'T
KNOW, WHAT ARE THE GAPS WHEN IT
COMES TO SLEEP APNEA, AND CARE
OF WOMEN.
AND I TOOK THIS SLIDE FROM HER
WORK AS AN ADVOCATE, REALLY
HIGHLIGHTING THAT ONE IN FIVE
WOMEN HAVE SLEEP APNEA, THAT
MOST WOMEN ARE UNDIAGNOSED AND
UNTREATED AND OBVIOUSLY WE NEED
TO DO BETTER WITH THAT.
SO I THINK SHE REALLY CENTERED
WHY WE'RE DOING THIS.
WE TALKED ABOUT HOW OBSTRUCTIVE
SLEEP APNEAS LIKE HYPERTENSION
AND BY THAT, I THINK HE WAS
TALKING ABOUT MANY OF THE
DIFFERENCES IN TERMS OF
DEMOGRAPHICS THAT BOTH OSA AND
HYPERTENSION AFFECT MEN AND
WOMEN DIFFERENTLY, THERE ARE
RACIAL AND ETHNIC DIFFERENCES,
AGE DIFFERENCES, AND THAT WAS A
REALLY INTERESTING PERSPECTIVE.
I THINK THE OTHER THINGS THAT HE
TRIED TO HIGHLIGHT ARE THAT
THERE'S AN INCREDIBLY LARGE
NUMBER OF PATIENTS WITH
OBSTRUCTIVE SLEEP APNEA OR
HYPERTENSION.
FOR MOST PATIENTS WITH
HYPERTENSION, YOU DON'T USE A
LOT OF COMPLEXITY.
YOU SORT OF TREAT THEM BECAUSE
WE HAVE A LOT OF TREATMENT
OPTIONS, YOU DON'T NEED A LOT OF
METRICS OTHER THAN BLOOD
PRESSURE, AND GIVEN THE NUMBERS
OF PATIENTS WITH OBSTRUCTIVE
SLEEP APNEA, ALL OF THIS
COMPLEXITY, DO WE NEED IT ALL OR
NOT, OR WHICH PATIENTS TO WE
REALLY NEED TO UNCOVER THAT
COMPLEXITY.
SO MOVING INTO SESSION ONE, THIS
WAS OUTCOMES ACROSS THE LIFESPAN
AND I THINK DR. ISAIAH REALLY
TALKED ABOUT THE HETEROGENEITY
IN PEDIATRIC OBSTRUCTIVE SLEEP
DISORDERED BREATHING AND AS HE
EMPHASIZED, IT'S SLEEP
DISORDERED BREATHING NOT JUST
OBSTRUCTIVE DISEASE BECAUSE
THERE IS SO MUCH VARIABILITY.
AND I THINK HIS WAS THE FIRST
TALK TO START TO HIGHLIGHT HOW
MUCH DATA WE HAVE, VERY LITTLE
OF WHICH WE USE, AND CAN WE USE
MACHINE LEARNING APPROACHES TO
TRY TO HELP US.
DR. SUSAN REDLINE REALLY GOT
INTO THE COMPLEXITY HERE THAT
WE'RE TRYING TO LINK REALLY EVEN
GENOTYPE WITH ENDOTYPE WITH
PHENOTYPE AND TRY TO PERSONALIZE
TREATMENT OUT COME, BUT THIS
PATHWAY, WE HAVE SOME IDEAS
WHERE WE'RE WORKING OUT SORT OF
HIGHER -- LOWER AROUSAL
THRESHOLD, THESE ENDO PHENOTYPES
BUT WE'RE JUST AT THE INFANCY OF
ALL OF THIS INFORMATION.
DR. NISHA AURORA FROM NYU KIND
OF BUILDING ON THIS, ALL OF OUR
EARLIER SPEAKERS SHOWED HER
RECENT RESULTS IN WHICH THE
FINDINGS WERE DIFFERENT IN MEN
VERSUS WOMEN WHEN YOU LOOKED AT
GLYCEMIC CONTROL.
AND SHE SAID SOMETHING WHICH
REALLY STRUCK WITH ME, STUCK
WITH ME, IS THAT WE MIGHT NEED
DIFFERENT ALGORITHMS OF
DIAGNOSIS AND TREATMENT BASED ON
SEX.
SO IF YOU'RE LOOKING FOR SLEEP
APNEA IN A WOMAN, MAYBE YOU NEED
PSG VERSUS HSAT.
AND SO AGAIN, REALLY
HIGHLIGHTING A RECENT FINDING OF
HOW TREATMENT OF SLEEP APNEA IN
MEN AND WOMEN CAN RESULT IN
DIFFERENT OUTCOMES.
DR. MACEY SPOKE ABOUT SLEEP
APNEA AND ITS EFFECTS ON
COGNITION IN THE BRAIN, WHETHER
OR NOT OSA IS AN ACCELERATED
FORM OF AGING.
I THOUGHT SOME OF THAT
PERSPECTIVE WAS REALLY
INTERESTING BUT ALSO THOUGHT IT
WAS REALLY INTERESTING TO THINK
ABOUT THE MAGNITUDE OF EFFECT OF
OBSTRUCTIVE SLEEP APNEA VERSUS
OTHER THINGS WE THINK ABOUT,
LIKE SLEEP DURATION AND
EXERCISE, AND THIS WILL BE
ANOTHER THEME, IS THAT IT MAY
NOT JUST BE SLEEP APNEA, WHICH
IT SORT OF PAINS ME TO SAY, IT
MAY BE OTHER FACTORS THAT ARE
RELATED TO SLEEP.
SESSION TWO WOS REALLY FO FOCUSD
ON OSA AND MENOPAUSE.
DR. FACCO PRESENTED THE MFMU
SLEEP OVERVIEW TRIAL.
I WAS AMAZED AT THE COMPLEXITY
OF THIS TRIAL AND LIKE THIS
LITTLE GIF HERE, I CANNOT WAIT
FOR THE RESULTS OF THIS TRIAL.
THIS IS AN INCREDIBLY COMPLEX
HARD STUDY TO DO, WHEN DO YOU
START SCREENING PREGNANT WOMEN
FOR SLEEP APNEA, WHEN DO YOU
TREAT THEM, HOW DO YOU GET THEM
ADHERENT WITH THERAPY?
I'M REALLY LOOKING FORWARD TO
THIS TRIAL.
DR. BOURJEILY REALLY IN HER
TALK, TALKED ABOUT MANY OF THE
CHALLENGES OF STUDYING THIS
POPULATION EVEN THOUGH IT IS A
UNIQUE OPPORTUNITY AND OBVIOUSLY
VERY IMPORTANT FROM A PUBLIC
HEALTH POINT OF VIEW.
HER POINT ABOUT NOT FOR GETTING
THE POSTPARTUM PERIOD WHEN
PEOPLE ARE INCREDIBLY SLEEP
DEPRIVED AND HAVE MANY NEW
RESPONSIBILITIES, I THOUGHT WAS
A GREAT REMINDER.
FINALLY DR. JOFFE SPEAKING ABOUT
SLEEP FRAGMENTATION IN
PERIMENOPAUSE PERIOD.
HER SLIDE HERE IF A PATIENT WITH
NIGHT SWEATS COME IN CLINIC, I
THINK WE THINK ABOUT OBSTRUCTIVE
SLEEP APNEA AND WE DON'T THINK
ABOUT ALL THE OTHER CHANGES THAT
ARE HAPPENING, AND I REALLY
ENJOYED HER LINE IN ONE OF HER
CONCLUDING SLIDES, AVOID
REDUCTIONISM, EXPAND
MULTIDIMENSIONAL UNDERSTANDING.
I THOUGHT THAT WAS A GREAT
THOUGHT AND A REMINDER WHEN WE
OFTEN REDUCE EVERYTHING TO
OBSTRUCTIVE SLEEP APNEA.
SESSION THREE FOCUSED ON
HETEROGENEITY OF OSA.
I THINK DR. PACK WON THE SLIDE
OF THE DAY FOR ALL THE DIFFERENT
OUT COME MEASURES AND THEY SEEM
TO BE BREEDING LIKE RABBITS,
AGAIN, A THEME OF COMPLEXITY,
WHAT ARE THE RIGHT MEASUREMENTS,
WHAT ARE THE RIGHT OUTCOMES.
AND HOW ARE WE GOING TO DEAL
WITH ALL THIS INFORMATION.
AND ANKIT GAVE A GREAT SUMMARY
TALK ABOUT MANY DIFFERENT
THINGS.
I THINK MACHINE LEARNING
APPROACHES BUT THIS ERA OF BIG
DATA AND HOW ARE WE GOING TO TRY
TO INCORPORATE ALL OF THIS
INFORMATION YOU SEE JUST A
REPRESENTATIVE SLIDE HERE.
AND DR. GAYANOVA, I THINK IS
STARTING TO LEAD THE WAY.
THIS WAS A GOOD EXAMPLE USING
MACHINE LEARNING APPROACHES.
SO SHE LOOKED AT DR. AURORA'S
HYPNOS TRIAL LOOKING AT GLYCEMIC
PROFILES IN THOSE WITH
OBSTRUCTIVE SLEEP APNEA TREATED
WITH PAP AND THE MAIN PARENT
STUDY DIDN'T FIND AN OVERALL
DIFFERENCE, BUT THEN WHEN YOU
APPLY SOME OF THESE MACHINE
LEARNING APPROACHES, YOU START
TO GET AT SOME OF THE
HETEROGENEITY AND VARIABILITY.
BUT AS A CAUTIONARY NOTE,
DR. WELLMAN LOOKED AT SOME
RECENT DATA WHERE PULSE OXIMETRY
IN WHITE SKINNED VERSUS
DARK-SKINNED PEOPLE MAY ACTUALLY
BE DIFFERENT, SO WE DON'T WANT
MACHINE LEARNING TO PERPETUATE
BIASES OR GOING BACK TO THE
80s SORT OF GARBAGE IN-GARBAGE
OUT.
SO MY TAKEAWAY FROM DAY ONE,
FROM ALL OF THE TALKS, IS THAT
THERE'S A TREMENDOUS AMOUNT OF
HETEROGENEITY, CERTAINLY
INCLUDING GENDER, AND THERE'S
UNIQUE BIOLOGY ACROSS THE
LIFESPAN IN WOMEN THAT PRESENTS
BOTH CHALLENGES AND
OPPORTUNITIES TO REALLY IMPROVE
THE HEALTH OF OUR PATIENTS.
THE OVERWHELMING AMOUNTS OF
INFORMATION THAT WE'RE
COLLECTING REFLECTS REALLY THE
PROTEOME NATURE OF SLEEP, IT'S
NOT JUST SLEEP DISORDER
BREATHING, IT'S HOW MUCH YOU
SLEEP, WHEN YOU SLEEP, THINGS
LIKE THAT, AND THEN MACHINE
LEARNING APPROACHES OFFER
AMAZING POTENTIAL BUT DO HAVE
RISKS.
IT TOOK US QUITE A WHILE TO GET
TO WEARABLES BUT IT SEEMS THE
AMOUNT OF INFORMATION WE'RE
ABOUT TO BE COLLECTING IS JUST
GOING TO INCREASE EXPONENTIALLY.
SO THANK YOU AGAIN TO ALL OF OUR
SPEAKERS.
AND I CAN'T WAIT TO SEE WHAT DAY
TWO BRINGS.
THANK YOU VERY MUCH.
>> SO TAKING OFF ON THE DAY ONE,
I THINK WE DISCUSSED A LOT ABOUT
THE HETEROGENEITY IN TERMS OF
CHARACTERIZING OSA, IN TERMS OF
THE MANIFESTATION OF OSA, THE
DISEASE PROCESS AND SO ON.
AND ONE QUESTION I THINK KEPT
COMING ACROSS THROUGH ALL THE
DISCUSSIONS WAS OKAY, NOW WE
HAVE -- WHAT ABOUT THE
TREATMENT, HOW DO WE TACKLE
HETEROGENEITY IN TREATMENT AND
WHAT ARE THE CHALLENGES THERE
AND WHAT ARE THE OPPORTUNITIES
THERE.
SO ONE OF THE FIRST THINGS I
FEEL THAT IS NEEDED WHEN WE TALK
ABOUT TREATMENT IS WHAT IS THE
DEFINITION OF A RESPONDER VERSUS
NON-RESPONDER.
SO WHEN YOU'RE LOOKING AT
TREATMENT, YOU KNOW, DIFFERENT
TYPES OF TREATMENT AND TREATMENT
RESPONSE, WHAT IS THE DEFINITION
OF A RESPONDER AND WHO DO WE
CONSIDER AS A RESPONDER, DO WE
STICK TO WHAT THE DEFINITIONS
HAVE BEEN SO FAR OR ARE WE NOW
GOING TO ATTEMPT TO INCORPORATE
HETEROGENEITY INTO TERMS OF THE
DEFINITION.
SO IS IT A ONE SIZE FITS ALL
DEFINITION FOR WHAT WE SORT OF
TERM AS RESPONDER?
IS IT GOING TO BE ONLY BASED ON,
YOU KNOW, SORT OF THE
CHARACTERISTICS, THE SYMPTOMS,
OR ARE WE GOING TO LOOK AT A
MORE HOLISTIC APPROACH AND IF WE
DO THAT, HOW DO THE STATISTICS
PLAY OUT AND HOW CAN WE SORT OF
TACKLE THAT.
THE DEFINITION OF A RESPONDER
AND NON-RESPONDER IS ESPECIALLY
CRUCIAL WHEN YOU'RE CONSIDERING
PERSONALIZING TREATMENT AND THE
DIFFERENT TREATMENT MODALITIES.
SO AS WE PROGRESS TODAY, I'M
HOPING THAT CERTAIN DISCUSSIONS
AND QUESTIONS COME ABOUT THAT
CAN HELP US REFINE THIS, WHO IS
A RESPONDER VERSUS
NON-RESPONDER.
IN TERMS OF AGAIN TARGETING
THESE THERAPIES AND TARGETING
THE SPECIFIC POPULATIONS, ARE WE
GOING TO TARGET SYMPTOMS, ARE WE
GOING TO TARGET CHARACTERISTICS
OR ARE WE GOING TO TARGET BOTH
OF THEM OR A COMBINATION OF THEM
AND SO ON.
SO SOME OF THE OTHER SESSIONS
THROUGHOUT THE DAY ARE GOING TO
TACKLE IF THERE ARE COMBINATION
THERAPIES, COMBINATION OF
DIFFERENT DRUGS AND SO ON THAT
COULD BE USED TO TACKLE SYMPTOMS
OR THE PHYSIOLOGICAL
CHARACTERISTICS WHICH THEN SORT
OF HELP SYMPTOMS AND SO ON.
AND AGAIN, FOR THIS SCENARIO, IT
IS KEY TO KNOW WHAT IS THE
RESPONSE TO SORT OF TREATMENT
DEFINITION.
SO EVEN THOUGH YOU HAVE THESE
COMBINATION THERAPIES THAT ARE
GOING TO ATTEND TO SORT OF
MODIFY SOME OF THE PHENOTYPES,
THE ENDO TYPES, IS THE
DEFINITION STILL GOING TO BE
THAT A RESPONDER IS SOMEONE WHO
RESPONDS TO TREATMENT IN TERMS
OF AHI OR ARE WE GOING TO CHANGE
THAT DEFINITION.
SO THAT'S SOMETHING TO KEEP IN
MIND AS YOU HEAR ABOUT THESE
DIFFERENT TALKS, AND BRING TO
DISCUSSION, TO REALLY
EMPHASIZING THE HETEROGENEITY
NOW OF SHIFTING FROM
CHARACTERISTICS OF OSA AND THE
OUTCOMES TO ACTUALLY NOW
TREATMENT.
AGAIN THE COMBINATION THERAPY,
ARE THEY GOING TO TARGET THE
COMBINATION OF CHARACTERISTICS
OR ARE WE GOING TO TACKLE ONE OF
THEM AT A TIME, AND IF THEY ARE
TO BE COMBINED, HOW DO WE
PROCEED TO DO THAT.
WE'LL THEN SORT OF GO FORWARD
AND TALK ABOUT HETEROGENEOUS
EFFECTS, IN PERSONS WITH
INTELLECTUAL AND DEVELOPMENTAL
DISABILITIES, WHAT ARE THE
CHALLENGES WHEN IT COMES TO OSA
CHARACTERIZATION AS WELL AS
TREATMENT.
WHAT ARE THE SPECIFIC OUTCOMES
THAT SHOULD BE TARGETED?
ARE THEY GOING TO BE THE SAME,
ARE THEY GOING TO BE DIFFERENT,
WHAT SHOULD BE PRIORITIZED FOR
THIS POPULATION.
WHAT IS THE ROLE OF LONG TERM
MONITORING IN THESE POPULATIONS
AND IS THAT SOMETHING WE CAN
STOSORT OF USE TO NOT ONLY
ELUCIDATE HETEROGENEITY BUT ALSO
TACKLE SOME OF THE OUTCOMES OF
THE QUESTIONS WE HAD BEFORE.
THE HETEROGENEITY WITHIN THE
COMORBIDITIES IN THESE
POPULATIONS IS A CHALLENGE BUT
COULD ALSO BE AN OPPORTUNITY AND
COULD BE USED TO SORT OF ANSWER
SOME OF THE LONG-STANDING
QUESTIONS WE HAVE ABOUT OSA, SO
AS WE GO THROUGH THE OTHER
SESSION, YOU WILL HEAR ABOUT
DOWN SYNDROME AND SOME OF THE
OTHER VULNERABLE POPULATIONS AND
THE CHALLENGES THAT THAT
POPULATION PRESENTS AND HOW IT
COULD BE SORT OF USED TO
CHARACTERIZE THE HETEROGENEITY
IN OSA.
IN TERMS OF THE EMERGING
THERAPIES COMING ABOUT ON SCENE,
CPAP IS NOT THE ONLY THERAPY
ALTHOUGH IT'S BY FAR THE ONE
THAT'S SORT OF USED WIDELY, WHAT
IS ITS UTILITY IN VULNERABLE
POPULATIONS AND HOW DO WE SORT
OF TARGET OR LOOK AT THESE
EMERGING THERAPIES WITHIN THE
CONTEXT OF VULNERABLE
POPULATIONS, AND HOW DO THE
CHARACTERISTICS THAT WE SORT OF
DESCRIBE FROM DAY ONE, THE
DIFFERENT HETEROYES NAT HETEROGD
HETEROGENEOUS EFFECTS WE SAW ON
DAY ONE, HOW DO THEY PLAY IN
THIS WHOLE POPULATION.
SO HOPEFULLY SOME OF THE TALKS
YOU WILL HEAR THROUGHOUT THE DAY
WILL SHED LIGHT ON THAT AND
DURING THE DISCUSSION I URGE YOU
TO SHORT OF BRING THESE
QUESTIONS TO THE FOREFRONT.
ONE OF THE FACTORS THAT WE
SHOULD BE CONCENTRATING IN
EMERGING THERAPIES, IS IT AGAIN
GOING TO BE A SEQUENTIAL TRIAL,
ONE AFTER THE OTHER OR ARE WE
GOING TO TRY SOME COMBINATION AT
FIRST AND HAVE STRATEGIES THAT
WILL MOVE PERSONS TO ANOTHER
TREATMENT SHOULD THAT TREATMENT
FAIL.
AND FINALLY, WHEN WE ARE TALKING
ABOUT THE HETEROGENEITY, YOU
TALK ABOUT -- WE TALK ABOUT
CHARACTERISTICS AND OTHER THINGS
ON DAY ONE, WE ARE TALKING ABOUT
TREATMENT TODAY.
AT THE END, EVERYONE HAS A
QUESTION ALL THE TIME, HOW ARE
WE GOING TO IMPLEMENT THIS, HOW
ARE WE GOING TO BRING TO THE
CLINIC.
SO FROM DR. OWENS' SLIDE ON DAY
ONE, THE CHARGE WE HAD IN FRONT
OF US BY THE NHLBI AND THE NCDSR
IS HOW ARE WE GOING TO BRING
THIS TO THE CLINIC, WHAT ARE THE
CHALLENGES THAT REMAIN AND HOW
DO WE SORT OF TACKLE THEM.
SO AS YOU HEAR ABOUT THESE
TALKS, I WOULD URGE YOU TO BRING
TO DISCUSSION SOME OF THESE KEY
QUESTIONS THAT COULD BE
ADDRESSED.
SO THERE'S SEVERAL LEVELS OF
IMPLEMENTATION.
ULTIMATELY WE WANT THE SCIENCE
TO BENEFIT ALL RELEVANT
STAKEHOLDERS SO WHAT ARE THE
CHALLENGES THAT ARE PRESENTED
OVER THERE.
WE'LL BE GOING FROM DIAGNOSIS TO
TREATMENT MANAGEMENT AND THEN
FOLLOW-UP.
WHAT ARE THE CHALLENGES FOR
IMPLEMENTATION ACROSS THE
SPECTRUM FOR THESE THREE SORT OF
DOMAINS, AND THEN THE BIG
QUESTION IS ARE WE READY TO
PERSONALIZE CLINICAL TRIALS.
SO WE ARE TALKING ABOUT
HETEROGENEITY SO MUCH, IN TERMS
OF CHARACTERISTICS, IN TERMS OF
THE TREATMENT, ARE WE READY TO
EMBED THAT HETEROGENEITY INTO
THE DESIGN OF OUR CLINICAL
TRIALS.
OR COULD THEY BE USED TO E ENRIH
THE RECRUITMENT THAT COULD
HAPPEN IN CLINICAL TRIALS.
WHAT ARE THE GUIDELINES AND
STANDARDS FOR IMPLEMENTATION?
THIS IS SOMETHING THAT
IMPLEMENTATION SCIENCE IS SORT
OF A FIELD IN ITSELF, AND HOW
CAN WE LEARN FROM THAT AND USE
TO OUR ADVANTAGE FOR SLEEP APNEA
PATIENTS AND ALL THE RELEVANT
STAKEHOLDERS.
SO LASTLY I WOULD WANT TO SORT
OF EMPHASIZE THE ROUND TABLE
DISCUSSIONS THAT WILL HAPPEN
TOWARD THE END OF THE DAY WHERE
SOME OF THESE QUESTION FROM DAY
ONE AND THE QUESTIONS THAT MAY
BE RAISED TODAY FROM DAY TWO
ALONG WITH THIS VIEW THAT -- HOW
CAN WE BRING ALL OF THESE THINGS
TO THE CLINIC, ONE OF THE
QUESTIONS THAT STILL REMAIN,
WHAT ARE THE RESEARCH THAT NEEDS
TO HAPPEN, I WOULD URGE EVERYONE
TO SORT OF BRING THESE QUESTIONS
TO THE ROUNDTABLE DISCUSSIONS
AND TRY AND SORT OF GAIN SOME
CONSENSUS, OR AT LEAST KNOW WHAT
THE FUTURE STEPS OR THE NEXT
STEPS ARE IN THAT DIRECTION.
SO WITH THAT, I'LL STOP OVER
HERE AND THEN I THINK IT'S TIME
FOR OUR FIRST SESSION OF THE
DAY.
>> THANK YOU SO MUCH FOR
WRAPPING THAT UP AND CERTAINLY
SUMMARIZING THE CONVERSATIONS ON
DAY ONE.
AND THEN ANKIT FOR FRAMING DAY
TWO.
SO NEXT UP, WE WILL INTRODUCE OR
RE-INTRODUCE ONE OF OUR
CO-CLAIRES, DR. ESRA TASALI,
PROFESSOR AT THE UNIVERSITY OF
CHICAGO WHO WORKS IN SLEEP AND
ENERGY METABOLISM, LOOKING AT
OSA IN METABOLIC OUTCOMES.
ALSO, AGAIN, ESRA IS A CHAIR OF
THE -- OR THE CURRENT CHAIR OF
THE NIH SLEEP DISORDERS RESEARCH
ADVISORY BOARD, SO ESRA, ARE YOU
READY TO TAKE IT AWAY?
>> YES, YES.
LET ME SEE.
I NEED TO SHARE MY SLIDES,
MARISHKA.
I DID THIS BEFORE, BUT HOLD ON.
I APOLOGIZE, EVERYONE.
>
>> SO WE HEARD EXCELLENT TALKS
YESTERDAY AND MY TASK TODAY IS
TO ADDRESS THIS CHALLENGING
QUESTION.
SO CAN WE IDENTIFY RESPONDERS
VERSUS NON-RESPONDERS?
AND AT THE END OF MY TALK, I MAY
LEAVE YOU WITH MORE QUESTIONS
THAN ANSWERS, BUT I HOPE I WOULD
LIKE THAT THIS WILL HELP FOR THE
DISCUSSIONS LATER.
SO I THINK FIRST WE NEED TO
UNDERSTAND THAT AS HAS BEEN
MENTIONED, THAT THE TREATMENT
RESPONSE IS MULTILEVEL AND
MULTIFACTORIAL IN NATURE.
SO I DID THESE, FOR SIMPLICITY,
THESE THREE LEVELS: WHO TO
STUDY, HOW DO WE TREAT, AND WHAT
END POINTS ARE WE LOOKING AT.
SO WHAT IS OUR STUDY POPULATION
FOR SIMPLICITY, WE NEED TO
UNDERSTAND THAT THERE IS A
TARGET POPULATION, WE WOULD LIKE
THE INFORMATION TO GET
INFORMATION ABOUT IDEALLY, THEN
THERE'S THE ACTUAL POPULATION,
PEOPLE WHOM OUR SAMPLE WILL BE
DRAWN BASED ON OUR ELIGIBILITY
CRITERIA, AND THEN THERE IS THE
SAMPLE WHICH IS A SUBSET OF THE
ACTUAL POPULATION.
SO WE NEED TO CONSIDER THESE
FACTORS WHEN EXAMINING THE
HETEROYES NA
HETEROGENEITY.
SO AS MENTIONED EARLIER, THERE
ARE DEMOGRAPHIC FACTORS AND
PHENOTYPES AND CO-MORBID
CONDITIONS AND DURATION OF
EXPOSURE WHICH ALSO WAS
MENTIONED AND DISTINCT
PHENOTYPES THAT CAN INFLUENCE
THE TREATMENT RESPONSE.
SO HOW DO H WE APPLY TREATMENT S
ALSO IMPORTANT, WHETHER IT'S
SINGLE OR COMBINED TREATMENTS,
THE DELIVERY METHODS FOR
TREATMENTS, TREATMENT DURATION,
TREATMENT ADHERENCE AND
MONITORING AND ACCESS TO
TREATMENT.
AND IN TERMS OF END POINTS,
SHOULD WE BE FOCUSING ON SLEEP
APNEA METRICS, OR SHOULD WE BE
FOCUSING ON DAY TIME SLEEPINESS
OR OTHER ESTIMATES VERSUS
BIOLOGICAL END POINTS.
AND WHAT ARE THE CLINICAL
MEANINGFULNESS AND REA VERSE
AREANDREVERSIBILITY OF THESE OUS
AND WHAT ARE THE CUTOFFS AND
METRICS WE'RE USING TO DEFINE AN
OUTCOME TO STRATIFY OUR
RESPONDERS AND NON-RESPONDERS.
BEFORE MOVING ON AS I WAS
RESEARCHING THIS TOPIC, I CAME
ACROSS THIS STATISTICAL
METHODOLOGICAL PAPER AND MOST OF
YOU MIGHT BE FAMILIAR WITH THIS,
A RESPONDER AS WE DEFINE, AS WE
HEARD, IS AN INDIVIDUAL FOR WHOM
AN INTERVENTION IS BENEFICIAL.
HOWEVER, THERE'S A COMMON NOTION
THAT INDIVIDUALS WHO BENEFIT
FROM TREATMENT AS RESPONDERS ARE
THOSE WHO HAVE GREATER ROOM FOR
IMPROVEMENT, BUT STATISTICIANS
GIVE US A CAUTION FOR
PARTICULARLY POSTDOC SECONDARY
ANALYSES, BECAUSE DIVIDING
GROUPS BY THE OUTCOMES BEING
TESTED WHEN THERE'S NO OVERALL
EFFECT CAN LEAD TO SERIOUS
MISINTERPRETATION OF THE DATA,
BECAUSE YOU WOULD EXPECT THAT
INDIVIDUALS WITH LOW LEVELS OF A
PARTICULAR OUTCOME AT BASELINE
WOULD IMPROVE, AND, THEREFORE,
THERE NEEDS TO BE A
CONSIDERATION FOR A CONTROL
GROUP, CONTROL POPULATION FOR
RIGOROUS RESEARCH.
IN THIS
TREATMENT RESPONSE.
WHEN WE LOOK AT THE LITERATURE,
ONE APPROACH TO PREDICT
TREATMENT RESPONSE IS TO DO
CLUSTER ANALYSES, IN OTHER
WORDS, LOOKING AT BASELINE
PHENOTYPIC CHARACTERISTICS, AND
AS YOU CAN SEE HERE, A JARRED
RESPONSE HAS BEEN USED IN
MULTIPLE META-ANALYSES AND
SYSTEMIC ANALYSES IN THIS
RECENTLY PUBLISHED LARGE
PROSPECTIVE COHORT, EUROPEAN
COHORT, EVEN THOUGH AHI RESPONSE
REMAINS STABLE, THERE WAS
VARIABLE RESPONSE TO SLEEPINESS
BASED ON BASELINE CLUSTERS.
HOW ABOUT METABOLIC OUTCOMES?
WE KNOW THAT EXCESS WEIGHT,
SLEEP APNEA AND IMPAIRMENTS IN
GLUCOSE METABOLISM ARE HIGHLY
INTERRELATED.
WE KNOW THAT OBESITY HAS SEVERAL
COMORBIDITIES AND SLEEP APNEA
AND PREDIABETES, DIABETES CAN
COEXIST, AND WE ALSO KNOW EXCESS
WEIGHT ITSELF CAN LEAD TO
INSULIN RESISTANCE AND DIABETES
THROUGH VARIOUS MECHANISMS,
THROUGH INFLAMMATION, THROUGH
DEFECTS IN FAT METABOLISM, AND
THROUGH DOWNSTREAM EFFECTS IN
MITOCHONDRIAL METABOLISM LEAD
BELEADINGTO IMPAIRED GLUCOSE ANT
UTILIZATION.
WE ALSO KNOW THAT TO MAINTAIN
NORMAL GLUCOSE TOLERANCE,
INDIVIDUALS HAVE TO UPREGULATE
THEIR INSULIN SECRETION RELATIVE
TO THE DEGREE OF INSULIN
RESISTANCE.
BUT ON THE OTHER HAND, EVEN
THOUGH THERE IS THIS DEPENDENCY
ON EXCESS WEIGHT, THERE HAS BEEN
FOR THE PAST TWO DECADE STRONG
LITERATURE SUGGESTING THAT
THROUGH POTENTIAL BIOLOGICAL
PATHWAYS, SLEEP AP FE APNEA MAYE
INDEPENDENTLY LINKED TO
IMPAIRMENTS IN GLUCOSE
METABOLISM AND SYNTHETIC
ACTIVATION HAS BEEN ONE OF THEM,
ALTERED LIPID METABOLISMS HAVE
ALSO BEEN STUDIED, INFLAMMATION
AND OTHERS.
SO ONE OTHER WAY TO LOOK AT THIS
HETEROGENEITY IN TREATMENT
RESPONSE IS POTENTIALLY TO STUDY
YOUNG LEAN INDIVIDUALS AND WE
DID THAT.
THESE WERE YOUNG LEAN MEN WITH
NO CARDIOBOLG DISEASE, AND CARDD
CONTROLS WERE MATCHED FOR AGE,
BMI AND DIABETES RISK.
AND WHAT WE SAW WAS THAT THESE
OTHERWISE HEALTHY INDIVIDUALS
WITH NO CARDIOMETABOLIC DISEASE
HAVE TO SECRETE 37% HIGHER
INSULIN SECRETION TO MAINTAIN A
SIMILAR LEVEL OF GLUCOSE
TOLERANCE AND THEY BEHAVED AS IF
THEY WERE OBESE NORMAL GLUCOSE
TOLERANCE SUBJECTS WHEN WE
CONSIDER THE TRAJECTORY, GLUCOSE
TRAJECTORY INTO DEVELOPMENT OF
TYPE 2 DIABETES.
ANOTHER INTERESTING POPULATION
AND A DISTINCT POPULATION THAT
WE HAVE AN OPPORTUNITY TO STUDY
ARE WOMEN WITH POLYCYSTIC
OVARIAN SYNDROME.
THESE ARE PERIMENOPAUSAL WOMEN
WHO ARE HAVING HIGH TESTOSTERONE
LEVELS, THEIR CHARACTERIZED BY
OBESITY AND INSULIN RESISTANCE,
AND SLEEP APNEA IS HIGHLY
PREVALENT IN THIS POPULATION AND
THE RISK OF SEVERITY OF SLEEP
APNEA IS HIGHLY CORRELATED WITH
METABOLIC IMPAIRMENTS.
SO THEY HAVE AN EARLY ONSET
DIABETES AND CARDIOVASCULAR
RISK.
WE STUDIED THIS POPULATION SOME
YEARS AGO, AND TO MY KNOWLEDGE,
THERE HAS NOT BEEN INTERVENTION
STUDIES IN THIS POPULATION.
ANOTHER POPULATION WE COULD
LEARN FROM IS TYPE 1 DIABETES.
WE NOW KNOW THAT SLEEP APNEA IS
NOT JUST ABOUT TYPE 2 DIABETES
BUT IT'S ALSO INCREASED IN
PREVALENCE IN TYPE WITH AND IN
THIS PARTICULAR STUDY, WE DID
NOT ASSESS SLEEP APNEA BUT WE
SAW WITH LARGE INTERAND
INTRA-INDIVIDUAL VARIABILITY IN
SLEEP AND GLYCEMIC
CHARACTERISTICS IN REAL LIFE
SETTINGS IN THESE PATIENTS.
AND OBJECTIVELY MEASURED SLEEP
QUALITY WAS ASSOCIATED WITH
OVERNIGHT GLYCEMIC VARIABILITY
AND YOU CAN APPRECIATE NIGHT
WITH POOR SLEEP QUALITY SHOWED
HIGHER GLYCEMIC VARIABILITY EVEN
AT AN INDIVIDUAL PATIENT LEVEL.
WE ALSO KNOW THAT INCREASED
SYMPATHETIC ACTIVITY CAN WORSEN
GLUCOSE CONTROL AND WE KNOW THAT
SLEEP APNEA INCREASES
SYMPATHETIC ACTIVITY, BOTH
COMPARED TO LEAN AND OBESE
CONTROL, BUT INTERESTINGLY,
ALSO, WHEN WE DO CPAP WI WITH
WITHDRAWRL, IMMEDIATELY AFTER
THAT THERE IS INCREASED
SYMPATHETIC ACTIVITY.
INDEED SOME OF THE STUDIES
RANDOMIZED CONTROL TRIALS HAVE
SHOWN THAT EVEN AS LITTLE AS ONE
NIGHT OF C PACK WITHDRAWAL CAN
INCREASE NOCTURNAL GLUCOSE
LEVEL, INCREASED FREE FATTY
ACIDS AND CORTISOL.
SO TO ADDRESS THIS QUESTION
ABOUT CPAP USE TO IMPROVE
METABOLIC OUTCOMES, WE FIRST
CONDUCTED A PROOF OF CONCEPT
STUDY, A RANDOMIZED CONTROL
STUDY LED BY DR. PAMIDI AND WE
STUDIED PREDIABETIC PATIENTS
UNDER TWO CONDITIONS, IN AN
UNTREATED CONDITION AND TREATED
CONDITION, FOR TWO WEEKS, CPAP
TREATMENT WAS ADMINISTERED AT
NIGHT UNDER FULL SUPERVISION IN
THE LABORATORY AND SUBJECTS WERE
ALLOWED TO CONTINUE THEIR DAILY
ACTIVITY DURING THE DAY.
WHEN WE DID THIS, WE WERE ABLE
TO, IF I MAY SAY THAT, TURN OFF
THE DISEASE STATE AND NORMALIZE
OSA SEVERITY INDICES IN THIS
PARTICULAR STUDY, THE
TRADITIONAL INDICES AT LEAST,
AND WHAT WE SAW WAS IMPROVEMENT
IN GLUCOSE LEVELS, INSULIN
SENSITIVITY, AND SYMPATHETIC
ACTIVITY AS MEASURED BY
NOREPINEPHRINE LEVELS.
IN A FOLLOW-UP APPLICATION WE
ALSO SHOWED THAT CPAP TREATMENT
REDUCES NOT ONLY NIGHTTIME
RESTING HEART RATE LEVELS BUT
ALSO DURING THE DAY TIME OVER
THE COURSE OF TWO-WEEK
TREATMENT, RESTING HEART RATE
IMPROVED AFTER CPAP TREATMENT.
AND WE KNOW THAT EVEN ONE BEAT
OF INCREASE IN RESTING HEART
RATE CAN INCREASE MORTALITY AND
MORBIDITY, SO THERE IS A
CARRYOVER EFFECT OF NIGHTTIME
TREATMENT TO THE DAY TIME IN
REAL LIFE SETTINGS.
SIMILARLY, A RECENT PUBLICATION
BY DR. REDLINE'S GROUP AND
AZARBARZIN'S WORK HAS SHOWN THAT
A GREATER PRE-TREATMENT DELTA HR
METRIC IS ASSOCIATED WITH
GREATER CPAP RELATED PROTECTION
AGAINST ADVERSE CARDIOVASCULAR
OUTCOMES.
THIS IS DATA POST HOC A ANALYSIS
FROM THE TRIAL.
WE KNOW IT IS HIGHLY VARIABLE IN
REAL LIFE, DEPENDING ON WHAT
POPULATION YOU STUDY, THERE IS
LESS RESPONSE IN TYPE 2 DIAB
2 DIABETICS, THERE IS CONSENSUS
ON IMPROVEMENT IN INSULIN
RESISTANCE IN PERSONS WITHOUT
DIABETES, BUT ALSO RECENT TRIALS
LIKE SAVE STUDY, WHERE WE
INCLUDE PATIENTS WITH CO-MORBID
CARDIOVASCULAR DISEASE, FOUND NO
OVERALL EFFECT ON PREDIABETES OR
DIABETES OUTCOMES AS MEASURED BY
PLASMA GLUCOSE OR A1C, BUT THERE
WAS SOME SIGNAL INTERESTINGLY
FOR A PROTECTIVE ROLE OF CPAP IN
WOMEN WITH DIABETES.
AND THEN WE HEARD ABOUT THE
HYPNOS TRIAL, ALSO OVERALL NO
EFFECT BUT CPAP MAY IMPROVE
GLYCEMIC VARIABILITY IN WOMEN.
SO WHY IN THE REAL WORLD THERE
IS A LOW OR NO CPAP ADHERENCE,
THIS LARGE FRENCH STUDY LOOKED
AT ALMOST 500,000 PATIENTS FROM
THE DATABASE, AND FOUND THAT
CPAP TERMINATION RATE WAS ABOUT
48% AT THREE YEARS.
BUT THE DEFINITION OF CPAP
TERMINATION, I WOULD LIKE TO
POINT OUT, WAS BASED ON CPAP
REVERSEMENTS AND TRIGGERED BY
THE RESPIRATORY PHYSICIAN OR
SLEEP SPECIALIST USING A CPAP
USAGE OF LESS THAN FOUR HOURS
PER NIGHT OR VERY LOW USAGE OR
NO PERCEIVED BENEFIT.
SO I THINK I WOULD LIKE TO AT
LEAST PROPOSE A MISSING LINK
HERE, AND THIS IS HOW WE DEFINE
CPAP TREATMENT ADHERENCE.
WHAT IS THE OPTIMAL NIGHT LEIDOS
FOR AN INDIVIDUAL PATIENT, AND
WHAT IS THE GOAL FOR CPAP
SUCCESS?
I'M GOING TO GIVE YOU A COMMON
CLINICAL SCENARIO.
A PATIENT COMES IN AND SAYS HOW
MUCH DO I NEED TO USE THE CPAP
MACHINE TO GET BETTER, DOCTOR?
AND THE PROVIDER SAYS, THE MORE
YOU USE THE BETTER.
ACTUALLY IF YOU DON'T USE IT, AT
LEAST FOUR HOURS PER NIGHT, THEY
WILL TAKE YOUR MACHINE AWAY.
THIS ADVICE IS BASED OND
MEDICARE CRITERIA, CPAP WEAR
TIME GREATER THAN FOUR HOURS PER
NIGHT, IS CONSIDERED AS
ADHERENT, AND THE PATIENT COMES
BACK AND SAYS, YOU KEEP TELLING
ME I SHOULD USE THIS MACHINE
MORE, DOCTOR, BUT I WEAR MY MASK
ALL NIGHT EVERY NIGHT.
THIS IS JUST HOW I SLEEP, YOU
KNOW?
PATIENTS' HABITUAL SLEEP
PATTERNS CAN BE VARIABLE FROM
NIGHT TO NIGHT AND THIS IS
HIGHLY LIKELY HERE.
SO THIS PATIENT WAS NOT GIVEN A
CLEAR CPAP SUCCESS GOAL, AND
THIS PATIENT'S CPAP TREATMENT IS
NOT TAILORED OR PERSONALIZED TO
THEIR NIGHTLY SLEEP PATTERNS.
AND WE KNOW FROM LARGE
LITERATURE THAT SLEEP PATTERNS
ARE HIGHLY VARIABLE NOT ONLY
NIGHT TO NIGHT BUT ALSO PERSON
TO PERSON.
THIS IS LARGE POPULATION DATA
WITH VARIABLES OF OVER 120,000
INDIVIDUALS WITH UP TO TWO YEARS
OBJECTIVE SLEEP MONITORING.
AS YOU CAN SEE THOUGH EVEN MEAN
SLEEP DURATIONS ARE SIMILAR IN
DIFFERENT PERSONS, THEIR SLEEP
PATTERNS ARE HIGHLY VARIABLE.
THIS IS CLINICAL KAYDAY DATA ONL
THAT IS ONGOING ON NIGHT TO
NIGHT VARIABILITY IN TIME IN BED
OVER FIVE TO SIX MONTH PERIOD IN
DIFFERENT SLEEP APNEA PATIENTS
AND YOU CAN APPRECIATE THE
VARIABILITY IN SLEEP PATTERNS.
SO WE WOULD LIKE TO PROPOSE AND
WE DEVELOPED A NEW CPAP
ADHERENCE METRIC WHICH I CALL
PERCENT CPAP ADHERENCE, AND THIS
IS GOING BACK TO PUNJABI'S TALK,
A NEW SORT OF SIMPLICITY, A NEW
SIMPLE DIGITAL TOOL TOWARDS
POTENTIALLY PERSONALIZED OSA
CARE.
THIS WAS, I WOULD LIKE TO POINT
OUT, A USER CENTERED DESIGN
MEANING THAT PATIENTS THEMSELVES
HELPED US DEVELOP THIS TOOL,
THIS IS AND APP AND WE ALSO HAVE
A DASHBOARD, BUT IMPORTANTLY IT
PROVIDES PATIENTS TO HAVE A
CLEAR GOAL, 100% ADHERENCE, AND
IT INTEGRATES THROUGH VARIABLES
THE TIME IN BED INFORMATION AND
THE THERAPY IS -- THERAPY
SUCCESS THAT THE PATIENTS ARE
LOOKING AT EVERY MORNING ON
THEIR APP IS TAILORED NIGHT BY
NIGHT AND FOLLOWS THEIR NIGHTLY
SLEEP PATTERNS.
IN THIS PARTICULAR CASE, FOR
EXAMPLE, ACTUAL CPAP SUCCESS WAS
ONLY 51% BECAUSE THE PATIENT
SPENT TIME IN BED FOR EIGHT
HOURS, AND THESE ARE FROM LAST
WEEK, I BELIEVE, FROM A PATIENT
WHO'S IN OUR TRIAL.
AS YOU CAN SEE THE PATIENT IS
100% ADHERENT TO CPAP DESPITE
VARIABLE MASK ON DURATION, WHICH
CURRENTLY WE ARE BASING ALL OUR
ADHERENCE TREATMENT CRITERIA,
ONE NIGHT THE TIME IN BED WAS
FIVE HOURS 35 MINUTES AND THE
OTHER NIGHT THE TIME IN BED WAS
7 HOURS AND 46 MINUTES.
SO THIS MISSING LINK, I THINK
THAT OUR CURRENT DEFINITION OF
FOUR HOUR CPAP MASK WEAR IS IN
MY OPINION ARBITRARY AND COULD
BE HIGHLY MISLEADING AND COULD
BE A FACTOR IN EXPLAINING
VARIABILITY IN TREATMENT
RESPONSE.
FOR EXAMPLE, WE CAN LOOK AT
THESE TWO PATIENTS AND BECAUSE
THIS PATIENT DID NOT USE THEIR
MACHINE FOUR HOURS OR MORE, THEY
COULD BE CONSIDERED AS NOT
ADHERENT PER CERTAIN CRITERIA
BUT THEY ARE USING IT 93% OF
TIME THEY SPEND IN BED AND VICE
VERSA.
SO I THINK THAT THERE IS ALSO AN
IMPORTANT IMPLICATION ON HEALTH
EQUITY BECAUSE PEOPLE'S SLEEP
TIMES MAY VARY, ESPECIALLY GIVEN
THE KNOWN RACIAL/ETHNIC AND
SOCIOECONOMIC DIFFERENCES IN
SLEEP PATTERNS.
AND IN SUPPORT OF THIS IDEA OR
NOTION, OR METRIC, THERE HAS
BEEN A VERY LARGE DATA PUBLISHED
SHOWING A DOSE-RESPONSE
RELATIONSHIP BETWEEN CPAP USAGE
AND HEALTHCARE UTILIZATION IN
THIS CASE HOSPITALIZATION AND
EMERGENCY ROOM VISIT.
WITH BENEFITS SEEN EVEN WHEN
USAGE WAS AS LOW AS ONE TO TWO
HOURS PER NIGHT.
SO HOW ABOUT, AGAIN, GOING BACK
TO SIMPLICITY APPROACH, WE HAVE
ALL THESE DETAILED METRICS BUT
HOW ABOUT SIMPLY RESTORING SLEEP
QUALITY, WHAT HAPPENS TO SLOW
WAVE SLEEP, FOR EXAMPLE, ONE CAN
ALSO TALK ABOUT RM ABOUT REM SLT
I'M TAKING THE SLOW WAVE SLEEP
AS AN EXAMPLE HERE.
WE KNOW MANY OF US THAT PATIENTS
MAY NOT GET SLOW WAVE SLEEP AND
THEY RECOVER THEIR SLOW WAVE
SLEEP WITH CPAP THERAPY OR SLOW
WAVE ACTIVITY LEVELS AND SOME
PATIENTS MAY EVEN HAVE SLOW WAVE
ACTIVITY AT BASELINE AND EVEN
OUR FELLOWS KNOW THAT SLEEP
APNEA DURING SLOW WAVE, IF
ANYTHING, IS CURED AT THAT TIME.
SO WE ALSO KNOW THAT SLOW WAVE
SLEEP PLAYS AN IMPORTANT ROLE IN
GLUCOSE HOMEOSTASIS AND FUTURE
DIABETES RISK.
THIS IS LARGE PO POPULATION BASD
DATA THAT WAS PUBLISHED TO
SUGGEST THAT SLOW WAVE SLEEP
PREDICTS NEXT DAY GLUCOSE
REGULATION, AND OUR EXPERIMENTAL
DATA, AND DR. PUNJABI'S GROUP
PUBLISHED SIMILAR RESULTS THAT
IF YOU WERE TO SUPPRESS SLOW
WAVE SLEEP USING GLUCOSE
STIMULIIZATION, THAT WOULD
IMPAIR GLUCOSE ME TAB LIIZATION.
SUPPRESSION OF SLOW WAVE SLEEP
AND HYPOXEMIA COULD EXPLAIN
IMPAIRMENTS IN FREE FATTY ACID
METABOLISM IN SLEEP APNEA AND AS
YOU CAN SEE THAT IF SLOW WAVE
SLEEP IS PRESERVED, THERE IS
BETTER SUPPRESSION OF FREE FATTY
ACID METABOLISM SO LESS
DOWNSTREAM EFFECTS ON INSULIN
RESISTANCE IN THIS CASE.
AND WE ALSO HAVE VERY RECENT
DATA PUBLISHED IN HYPERTENSION
OF ABOUT 7,000 PATIENTS WITH
SLEEP APNEA HAS BEEN STUDIED,
AND WHAT THIS STUDY HAVE SHOWED
THAT DECREASED SLOW WAVE SLEEP
IS ASSOCIATED WITH A DOSE
DEPENDENT INCREASE IN ODDS OF
PREVALENT HYPERTENSION IN SLEEP
APNEA.
SO THOSE PATIENTS WHO PRESERVE
THEIR SLOW WAVE SLEEP AT
BASELINE HAD LESS LIKELIHOOD OF
BEING HYPERTENSIVE LATER.
SO WHETHER PRESERVATION OF SLOW
WAVE SLEEP AT BASELINE OR
RECOVERY FROM SLOW WAVE SLEEP
AFTER TREATMENT MAY EXPLAIN THE
VARIABILITY IN RESPONSE TO
TREATMENT IS ANOTHER RESEARCH
QUESTION.
AGAIN, WE HAVE MO MORE PROSPECTE
DATA FOR THE PROTECTIVE ROLE OF
SLOW WAVE SLEEP IN DIABETES AND
HYPERTENSION.
THIS IS OUR DATA FROM THE COHORT
FROM OUTCOMES OF SLEEP DISORDERS
IN OLDER MEN, BOTH SHOWING THAT
IF SLOW WAVE SLEEP IS PRESERVED,
THERE COULD BE LESS LIKELIHOOD
OF DIABETES OR HYPERTENSION.
AND I WOULD LIKE TO ALSO -- THIS
HAS BEEN MENTIONED SEVERAL
TIMES, IS IT ALL ABOUT SLEEP
APNEA, IS IT ALL ABOUT RESTORING
SLEEP QUALITY WITH OUR THERAPIES
IN SLEEP APNEA, I THINK I WOULD
ARGUE THAT INCORPORATING OTHER
SLEEP INTERVENTIONS IS A BETTER
WAY TO PERSONALIZE BEYOND OSA
TREATMENT BECAUSE WE KNOW THAT
THERE ARE FACTORS SUCH AS SLEEP
DURATION, SLEEP REGULARITY,
SLEEP TIMING AND CIRCADIAN
FACTORS THAT ARE ALL EQUALLY
IMPORTANT.
WITH THAT, WE HAVE PUBLISHED A
RANDOMIZED CONTROL TRIAL,
RESULTS FROM LOOKING AT THE
EFFECTS OF SLEEP EXTENSION ON
OBJECTIVELY ASSESSED ENERGY
INTAKE AMONG ADULTS WITH
OVERWEIGHT IN REAL LIFE
SETTINGS, AND WHAT WE WERE ABLE
TO SHOW THAT IF YOU CAN OPTIMIZE
SLEEP DURATION AND AS YOU CAN
PLEESHT THERE'S INDIVIDUAL
VARIABILITY, THEN WOULD YOU
DECREASE CLORK INTALK BY ABOUT
270 CAN I LOW CALORIES PER DAY,
AND THIS IS HIGHLY CLINICALLY
MEANINGFUL BECAUSE AS LITTLE AS
100 CAN I LOW CALORIES PER DAY
CAN INCREASE THE RISK FOR WEIGHT
GAIN.
WHAT I'M VERY EXCITED ABOUT,
THAT THIS STUDY WAS WELL
RECEIVED BY PEOPLE AROUND THE
GLOBE AND THE LAST SOCIAL MEDIA
POST FROM THIS STUDY THAT WAS
PUB LIRKED TWO YEARS AGO WAS
JUST LAST MONTH ON OCTOBER 21ST.
GIVEN THE SUCCESS AND INTEREST
IN THESE INTERESTING FINDINGS,
WE ARE NOW CONDUCTING A
RANDOMIZED CONTROLLED TRIAL TO
REALLY INCORPORATE OPTIMAL SLEEP
DURATION TO WEIGHT LOSS
INTERVENTIONS WITH HEALTHY DIET
AND PHYSICAL ACTIVITY.
THIS PARTICULAR STUDY ALSO USES
PERSONALIZED SLEEP INTERVENTION
TOOLS AND MHEALTH TECHNOLOGY
WITH HEALTH COACHING TO PROMOTE
WASTE LOSS AND IMPROVE CARDIOMED
METH BOLG HEALTH.
CARDIOMETABOLIC HEALTH.
SO KNOWING THE ENERGY BALANCE
MODEL OF OBESITY, WE KNOW THAT
IT IS -- COMPLEX BODY WEIGHT IS
REGULATED BY VARIOUS FACTORS,
WE'RE GOING TO HEAR MORE ABOUT
POTENTIALLY WEIGHT LOSS
TREATMENTS, PHARMACOLOGY
TREATMENTS FOR SLEEP APNEA IN
THE LATER TALKS, BUT IF I MAY
PROPOSE, I WOULD PROPOSE HEALTHY
SLEEP AS A NEW A APPETITE
SUPPRESSANT.
WE KNOW OVER THE PAST TWO
DECADES THAT SLEEP DEPRIVATION
INCREASES HUNGER, INCREASES
APPETITE THROUGH TWO MECHANISMS,
BOTH HOMEOSTATIC MECHANISMS
THROUGH HORMONES SUCH AS GR GHRN
AND ALSO REWARD MECHANISMS WHICH
HAS BEEN SHOWN TO BE ACTIVATED
WITH SLEEP DEPRIVATION AND
IMAGES STUDIES.
SO WHEN WE LOOK AT MATHEMATICAL
MODELING OF ENERGY BALANCE
DYNAMICS, WE KNOW THAT INCREASED
APPETITE PLAYS A GREATER ROLE
THAN DECREASED ENERGY
EXPENDITURE.
AND WE KNOW THAT DURING WEIGHT
LOSS, THERE IS A PERSISTENT
EFFORT NEEDED TO OVERCOME THE
INCREASE IN APPETITE.
THIS HAS BEEN IN THIS PARTICULAR
MODELING QUANTIFIED TO BE ABOUT
95 CA95 CAN I95 KILL 95KILOCALO.
>> ESRA, I WANT TO INTERJECT,
YOU'RE GETTING CLOSE TO TIME.
>> SURE.
LAST TWO SLIDES.
WE KNOW THAT AMERICAN HEART
ASSOCIATION, ACTUALLY WE WERE
ALL EXCITED THAT AMERICAN HEART
ASSOCIATION ADDED SLEEP TO
CARDIOVASCULAR HEALTH METRICS.
WE ALSO ARE VERY EXCITED THAT
AMERICAN DIABETES ASSOCIATION
ADDED SLEEP ASSESSMENT AS PART
OF PRECISION MEDICINE.
I THINK THAT WE HAVE AN
IMPORTANT RESPONSIBILITY HERE TO
INFORM THESE COMMUNITIES ON HOW
THAT WE CAN PERSONALIZE SLEEP
HEALTH.
I WILL SKIP THAT AND IN TERMS OF
RESEARCH GAPS AND OPPORTUNITIES,
I THINK THAT WE HAVE A GREAT
OPPORTUNITY FOR
INTERDISCIPLINARY AND
COLLABORATIVE APPROACH FOR
PERSONALIZED OSA CARE.
WE TALKED ABOUT THE GAP IN
RESEARCH FOR SEX AND GENDER
DIFFERENCES, WE WILL HEAR MORE
ABOUT POPULATIONS OF INTEREST.
I TALKED ABOUT SLOW WAVE SLEEP
BUT WE CAN DO MORE RESEARCH ON
REM SLEEP.
I THINK WE NEED TO DEFINITELY
DECIDE ON HOW WE DEFINE OUR
ADHERENCE TO TREATMENT.
THERE HAS BEEN DISCUSSION
YESTERDAY ABOUT THE
REVERSIBILITY OF AN OU OUTCOME H
TREATMENT AND WHAT IS THE CLUN
CAL BENEFIT.
FINALLY, I WOULD LIKE TO SAY
THERE CAN BE POTENTIALLY NOBLE
BIOMARKERS SUCH AS SYMPATHETIC
ACTIVITY MARKERS, HEART RATE
SURGES OR POTENTIALLY
MITOCHONDRIA FUNCTION CHANGES.
THOSE ARE INVOLVED IN THE KEY
PATHWAYS.
WITH THAT, I WOULD LIKE TO SAY
THANK YOU AND APOLOGIZE FOR THE
TECHNICALITIES.
>> IT HAPPENS.
BUT WE DO HAVE TIME FOR ONE
QUESTION AND IT LOOKS LIKE
DR. REDLINE HAS IT IN THE CHAT.
SUSAN, CAN YOU UNMUTE TO ASK
YOUR QUESTION?
>> REALLY GREAT TALK, ESRA, AND
I ESPECIALLY LIKED YOUR TALK
ABOUT N3 SLEEP.
WE KNOW FROM POPULATION STUDIES,
WOMEN ON AVERAGE HAVE MORE SLEEP
AND AS THEY AGE, THEY PRESERVE
THEIR N3 SLEEP.
SO CAN WE ACTUALLY LEVERAGE WHAT
WE KNOW NOW TO THINK ABOUT HOW
DIFFERENCES IN PRESERVATION OF
SLEEP GIVEN SLEEP APNEA MIGHT
ACTUALLY HELP US UNDERSTAND SOME
OF THE SEX DIFFERENCES IN
VULNERABILITY TO CARDIOMETABOLIC
DISEASE?
>> THIS IS AN EXCELLENT
QUESTION, SUSAN.
I THINK THAT CERTAINLY WE NEED
DO MORE QUANTITATIVE STUDIES
ACROSS THE COURSE OF HOW WOMEN
AGE, AND PRE AND POST MENOPAUSE,
SLOW WAVE SLEEP LEVELS AS YOU
KNOW, YOU KNOW, ARE CHANGING,
BUT THOSE POTENTIALLY WHO ARE
PRESERVING THEIR SLOW WAVE MAY
BE AT LOWER RISK AS THESE
POPULATION STUDIES SUGGEST.
SO I THINK THAT WE COULD CONDUCT
MORE MECHANISTIC STUDIES OR A
MORE -- BETTER DESIGN RANDOMIZED
CONTROL TRIALS REALLY POWER
TODAY LOOK AT THOSE SEX AND
GENDER DIFFERENCES.
>> AND ALSO SIMILARLY TO
UNDERSTAND PHYSIOLOGICALLY WHAT
ARE THE CHANGES IN SLOW WAVE
SLEEP, IS IT JUST A MEDIATOR OF
BETTER SLEEP CONTINUITY OR IS
THERE DIFFERENCES IN, YOU KNOW,
THE AUTONOMIC RESPONSES AT
NIGHT, ET CETERA.
>> EXACTLY.
I HAVEN'T SHOWN -- OUR PAPER IS
UNDER REVIEW WITH DR. BERSARD,
BUT WHEN WE DO EXPERIMENTALLY
RECOVER SLOW WAVE SLEEP, AND GET
IT BACK TO THE SUBJECTS WHAT IS
TAKEN AWAY, AMAZINGLY THEIR IS
LINDINSULIN SECRETORY RESPONSE -
APPROPRIATELY IF SLOW WAVE IS
THERE.
SO THESE FINDINGS HOPEFULLY WILL
BE PUBLISHED AND I THINK THERE
IS A LOT OF RESEARCH TO BE DONE
THERE.
>> THANK YOU.
>> WELL, THANK YOU, AND AS WE
QUEUE UP THE NEXT SESSION, AS
EVERYONE ON THE CALL IN THE
WORKSHOP ARE THINKING ABOUT THE
DISCUSSIONS AT THE END OF THE
DAY, THINKING ABOUT HOW SOME OF
THESE -- YOU KNOW, WITH THE
RESEARCH, IT'S GREAT AND WE'VE
HEARD KIND OF 360 DEGREES OF ALL
THE THINGS THAT ARE HAPPENING.
BUT TO THINK ABOUT HOW SOME OF
THESE PARTICULAR MEASURES COULD
BE MORE SPECIFIC AND MORE
SENSITIVE PARTICULARLY AND HOW
THESE NEW METRICS ARE IN SOME
WAYS CORRELATED WITH EACH OTHER,
AND HOW THEY COULD POTENTIALLY
BE MOVED TO THE CLINIC, AND SO
WE CAN CERTAINLY HAVE A FURTHER
DISCUSSION AT THE END OF THE
DAY, BUT WE WILL TURN IT OVER
NOW TO AARON LAPOSKY.
AARON, THANK YOU.
>> THANK YOU.
UNFORTUNATELY I CAN'T ACTIVATE
MY CAMERA BECAUSE IT SAYS MY
COMPUTER WON'T IDENTIFY IT SO I
APOLOGIZE FOR THAT, BUT I WILL
BE MODERATING THIS NEXT SESSION,
AGAIN, I'M A PROGRAM DIRECTOR IN
THE NATIONAL CENTER ON SLEEP
DISORDERS RESEARCH, AND I
OVERSEE A PORTFOLIO FOCUSED ON
CHRONOBIOLOGY AND ALSO
VENTILATORY CONTROL SCIENCE.
SO I'M HAPPY TO INTRODUCE THIS
SESSION WHICH IS LISTED IN THE
PROGRAM AS A HOT TOPIC AND IT'S
CONTINUING THE DISCUSSION ON
VARIOUS APPROACHES FOR TREATING
SLEEP DISORDERED BREATHING AND
POTENTIAL WAYS TO BE ABLE TO
PERSONALIZE THESE TREATMENTS FOR
PARTICULAR INDIVIDUALS, MAYBE
BASED ON THE PATHOBIOLOGY THAT
THEY HAVE FOR SLEEP DISORDERED
BREATHING.
SO THE SPEAKER IS DR. KLAR
YAGGI, PROFESSOR OF MEDICINE AND
DIRECTOR OF THE YALE PROGRAM IN
SLEEP MEDICINE AT THE YALE
UNIVERSITY SCHOOL OF MEDICINE.
THE TITLE OF HIS PRESENTATION
WILL FOCUS ON TREATING
OBSTRUCTIVE SLEEP APNEA WITH
PHARMACOTHERAPIES.
SO I'M HAPPY TO TURN THIS OVER
TO DR. KLAR.
DR. YAGGI, SORRY.
DR. YAGGI.
>> THAT'S JUST FINE.
THANK YOU VERY MUCH FOR THE
INVITATION AND PUTTING THIS
AMAZING WORKSHOP TOGETHER.
I MUST SAY YESTERDAY I LEFT SO
ENERGIZED THINKING ABOUT ALL THE
TOOLS THAT WE CAN LEVERAGE FROM
A.I. TO DR. PACK'S DISCUSSION OF
METABOLOMICS AND PRO AND PROTEO.
TODAY I WAS ASKED TO SPEAK ON
THE TOPIC OF ENDO PHENOTYPES AND
PARTICULARLY WITH RESPECT TO
PHARMACOTHERAPIES, AND FULL
DISCLOSURE, MY WORK HAS -- AND
THAT OF SOME OF MY MENTEES, HAS
REALLY FOCUSED ON BEING END US
USERS OF THESE TOOLS, AND I
TRULY BELIEVE THAT WE OWE A DEBT
OF GRATITUDE TO REALLY SOME OF
THE REALLY SMART PHYSIOLOGISTS
WHO HAVE BROUGHT SOME OF THESE
TOOLS TO THE RESEARCH COMMUNITY
SO WE CAN ASSESS THEIR CLINICAL
UTILITY AND VALIDITY, SUCH AS
ANDREW WELLMAN, SCOTT SANDS,
BRAD EDWARDS, AND CERTAINLY THE
WORK THAT'S GOING ON AT PENN
WITH SYMPTOM PHENOTYPES AND WITH
SWABS IMAGING, I THINK ALL ARE
GOING TO BE CRUCIAL IN
UNDERSTANDING THERAPEUTIC
POTENTIALS OF PHARMACOTHERAPIES.
I'M GOING TO SPEAK BRIEFLY ABOUT
A STUDY THAT WE HAVE JUST
STARTED THAT IS DOING JUST THAT,
LOOKING AT LEVERAGING IMAGING
AND SOME OF THESE PHYSIOLOGIC
TRAITS IN THE CONTEXT OF A
MECHANISTIC CLINICAL TRIAL FOR
OBSTRUCTIVE SLEEP APNEA CALLED
THE ADIPOSE STUDY.
I'M ALSO GOING TO MENTION SOME
WORK OF SEVERAL MENTEES THAT ARE
RELATED TO THIS TOPIC.
SO WE'RE GOING TO TALK BRIEFLY
TO GET EVERYONE ON THE SAME PAGE
ABOUT ENDOPHENOTYPES AND THEIR
CLINICAL POTENTIAL.
WE'RE GOING TO FOCUS FIRST ON
METABOLIC MODULATION AND ITS
IMPACT ON ANATOMY, MOVE TO
TALKING ABOUT NOR ADRENERGIC AND
ANTIMUSCARINICS AND THEIR IMPACT
ON GENERAL GENEOGLOSSIS AND UPE
MUSCLES E WE'RE GOING TO TALK
ABOUT SOME OF THE LITERATURE ON
HYPNOTICS AND AROUSAL THRESHOLD,
CARBONIC AN HIGH DRAIS
INHIBITORS AND VENTILATORY AND
STABILITY AND THEN FINISH OFF BY
TALKING ABOUT FUTURE
OPPORTUNITIES.
SO FOR MANY YEARS CERTAINLY WHEN
I STARTED OUT IN THE FIELD THE
PATHOGENESIS OF SLEEP APNEA WAS
THOUGHT REALLY TO ENTIRELY BE AN
ANATOMIC AND MECHANICAL ISSUE,
REALLY RELATED TO A BALANCE OF
FORCES AT PLAY.
ON THE SIDE OF THOSE FORCES THAT
ARE PROMOTING PATENCY ARE THE
PHARYNGEAL DILATOR MUSCLES, WE
KNOW GENIOGLOSSUS IS A MAJOR
PLAYER HERE AND PROMOTING AIRWAY
COLLAPSE IS THE NEGATIVE
PRESSURE OF INSPIRATION, AND
EXTRA LUMINAL POSITIVE PRESSURE
IMPOSED BY FAT OR ADIPOSE TISSUE
DEPOSITION IN SOME OF THESE
AIRWAY STRUCTURES OR HAVING A
SMALL MANDIBULAR SIZE.
THIS GAVE RISE TO THIS CONCEPT
OF CRITICAL CLOSING PRESSURE,
PCRIT AND THE HIGHLY COLLAPSABLE
UPPER AIRWAYS HAVE A POSITIVE
PCRIT AND MORE STABLE AIRWAYS,
IT TAKES MUCH MORE NEGATIVE
PRESSURE TO COLLAPSE THAT
AIRWAY.
REALLY OVER THE LAST 10 YEARS, I
THINK OUR UNDERSTANDING OF OSA
PATHOGENESIS HAS GROWN BY LEAPS
AND BOUNDS.
IN ADDITION TO THIS ANATOMICAL
PREDISPOSITION, WE NOW KNOW
THERE ARE A SERIES OF NON-AN
NON-ANATOMICAL TRAITS THAT ALSO
PREDISPOSE TO THE DEVELOPMENT OF
SLEEP APNEA.
YOU'VE HEARD ABOUT THESE ALREADY
THROUGHOUT THE CONFERENCE.
VENTILATORY CONTROL STABILITY,
LOOP GAIN, MUSCLE RESPONSIVENESS
OF THE UPPER AIRWAY, AND AROUSAL
THRESHOLD.
AND IT TURNS OUT THAT A MAJORITY
OF THESE PATIENTS MAY HAVE SLEEP
APNEA, RELATED TO THESE
NON-ANATOMICAL CAUSES RATHER
THAN JUST PURE ANATOMICAL
ISSUES.
AS WAS THE FOCUS OF THIS
WORKSHOP, NOT ALL PATIENTS GET
SLEEP APNEA FOR THE SAME REASON.
I THINK ONE OF THE APPEALS OF
THESE TRAITS IS THAT THEY'RE
ACTUALLY MEASURING PHYSIOLOGY
THAT IS OCCURRING DURING SLEEP
IN CONTRAST TO SOME OTHER
BIOMARKERS THAT ARE USED, AND
THEY LEVERAGE POLYSOMNOGRAPHY,
THE CURRENT WAY WE DIAGNOSE,
TREAT AND ASSESS OBSTRUCTIVE
SLEEP APNEA.
I THINK ANOTHER GREAT POTENTIAL
IS THAT THIS ACTUALLY MIGHT
REPRESENT A SCALABLE TECHNOLOGY.
WE'RE NOW DERIVING SOME OF THESE
TYPICAL TRAITS FROM STANDARD
POLYSONOGRAPHY, NOT JUST
ADVANCED PHYSIOLOGIC
LABORATORIES.
AND THE PROMISE OF THIS THERAPY
POTENTIALLY IS THAT TARGETING
THESE TRAITS MAY ALLOW US TO
REALLY MOVE INTO A MORE
PRECISION-BASED APPROACH TO
TREATING SLEEP APNEA.
INSTEAD OF A CPAP FOR ALL, THEN
SALVAGE THERAPY REALLY TARGETING
THESE TRAITS WITH VARIOUS
THERAPIES.
SO PERHAPS IT'S THE PATIENTS
WITH A SMALL COLLAPSIBLE AIRWAY
WHERE WEIGHT LOSS POSITIONAL
THERAPY OR APPLIANCE OR SURGERY
ARE BETTER APPROACHES.
THEN WE HAVE SOME PHARMACOLOGIC
THERAPIES THAT MAY ALLOW US TO
TARGET THEIR OVERLY SENSITIVE
INSULA TRI CONTROL SYSTEMS,
PHARMACOLOGIC AND NEW UPPER
AIRWAY NEUROSTIMULATION DEVICES
THAT MAY BE MORE HELPFUL AMONG
PATIENTS WITH POOR PHARYNGEAL
MUSCLE TONE AND SEDATIVE
HYPNOTICS OF COURSE TO TARGET
AROUSAL THRECIAL HOLD.
SO NOW WE'RE GOING TO MOVE INTO
STARTING TO TALK ABOUT THIS
ANATOMY AND METABOLIC
MODULATION.
HOT OFF THE PRESS LITERALLY
TODAY FROM THE LANCET IN THE
UNITED STATES, 75% OF PEOPLE IN
THIS COUNTRY ARE EITHER
OVERWEIGHT OR OBESE, WHICH IS
JUST MIND BLOWING.
AND IN FACT NOW, HALF OF U.S.
ADULTS WITH WOMEN ACTUALLY
LEADING THE WAY, MORE SO THAN
MEN, ARE ACTUALLY OBESE.
SO AN ENORMOUS PUBLIC HEALTH
BURDEN.
I THINK ONE OF THE THERAPEUTIC
PHARMACOLOGIC THERAPIES THAT
WE'RE ALL FAMILIAR WITH NOW ARE
THE GLP1 RECEPTOR AGONIST AND
THE STORY OF THESE THERAPIES IS
ACTUALLY QUITE REMARKABLE.
SO IN THE 1960s, IF WE
ADMINISTERED ORAL GLUCOSE, THAT
ELICITS A MUCH STRONGER INSULIN
RESPONSE AND GIVING THE EXACT
SAME AMOUNT OF GLUCOSE
INTRAVENOUSLY.
THIS PHENOMENON IS KNOWN AS THE
INCRETIN EFFECT.
IT REALLY HINTED THAT THERE WERE
SUBSTANCES PERHAPS HORMONES
BEING SECRETED BY INTRASITES IN
THE GUT THAT WERE ENHANCING
INSULIN SECRETION.
IN A NUMBER OF SCIENCES AROUND
THE 1960s AND 70s STUDYING
THE HELA MONSTER WHICH IS AN
ANIMAL THAT IS ADAPTED THAT CAN
ACTUALLY GO FOR MONTHS WITHOUT
EATING WHICH IS ACTUALLY VERY
HELPFUL WHEN YOU ARE LIVING IN A
DESERT HABITAT WHERE FOOD IS
SCARCE, IDENTIFIED A PEPTIDE IN
THE SALIVA OF THESE ANIMALS THAT
ACTUALLY ENDED UP SHARING VERY
SIMILAR STRUCTURAL AND
FUNCTIONAL SIMILARITY TO
GLUCAGON-TYPE PEPTIDE WHICH IS
SECRETED BY THE GUT AND WHICH WE
NOW KNOW STIMULATES INSULIN
SECRETION IN THE PANCREAS, SLOWS
GASTRIC EMPTYING AND REDUCES
APPETITE.
THESE MEDICATIONS HAVE REALLY
USHERED IN A NEW PARADIGM FOR
TREATING BOTH TYPE 2 DIABETES
AND OBESITY.
FOR THOSE INTERESTED
IRONICICALLY JUST THIS WEEK IN
THE "NEW YORK TIMES" MAGAZINE, I
THINK COMING OUT, IN FACT, THIS
WEEKEND, IS THE STORY OF THE
DEVELOPMENT OF THESE DRUGS AND
WHAT WE CAN LEARN FROM THE VENOM
OF ANIMALS.
I WAS VERY SURPRISED TO LEARN
THAT A VERY SIMILAR APPROACH WAS
USED TO DISCOVER ACE INHIBITORS.
BUT FOR YOUR READING PLEASURE IF
YOU HAVE A CHANCE TO LOOK AT
THIS.
SO WE KNOW SEMAGLUTIDE, PURELY A
GLP-1 AGONIST, AND AS WE'LL TALK
ABOUT ALSO THERE SEEMS TO BE A
GREATER MEAN PERCENTAGE OF
WEIGHT REDUCTION ASSOCIATED WITH
THESE MEDICATIONS AMONG WOMEN
COMPARED TO MEN, AND IN FACT
WITH RESPECT TO SEMAGLUTIDE,
FEMALE SEX WAS ASSOCIATED WITH A
HIGHER LIKELIHOOD OF LOSING 10%
OR GREATER BUT WE'VE NOW MOVED
INTO BOTH DOUBLE AND TRIPLE
HORMONE RECEPTOR AGONISTS.
WITH TIRZEPATIDE, WE'RE NOW
ACHIEVING A GREATER BODY WEIGHT
REDUCTION UP TO 15%, AGAIN
FEMALE SEX IS ASSOCIATED WITH A
GREATER REDUCTION IN BODY
WEIGHT, AND RETATRUTIDE WHICH IS
A TRIPLE HORMONE RECEPTOR
RESULTED IN WOMEN WITH NEARLY A
29% WEIGHT REDUCTION, WHICH NOW
WE'RE HITTING I THINK THE LOWER
RANGE OF EFFICACY OF BARIATRIC
SURGERY, WHICH IS QUITE
IMPRESSIVE.
ALTHOUGH WOMEN APPEAR TO HAVE A
SLIGHTLY GREATER WEIGHT LOSS
EFFECT WITH THESE MEDICATIONS,
WE DO KNOW FROM SOME OTHER
POOLED STUDIES THAT WEIGHT LOSS
ACTUALLY MAY BE MORE IMPACTFUL
IN IMPROVING SLEEP APNEA AMONG
MEN COMPARED TO WOMEN, THOUGH
THIS LIKELY VARIES A LITTLE BIT
WITH MENOPAUSAL STATUS.
WE KNOW THAT SEX DIFFERENCES
EXIST IN THE RESPONSE TO WEIGHT
LOSS INTERVENTIONS, AND CLEARLY
THIS IS A DOMAIN WHERE MORE DATA
IS NEEDED, PARTICULARLY AROUND
THE IMPACT OF THESE MEDICATIONS
ON SYMPTOMS OF SLEEP DISORDERED
BREATHING AND HOW MENOPAUSAL
STATUS MAY INFLUENCE THE
EFFICACY OF THESE.
BUT IT IS IN THIS CONTEXT THAT
WE JUST OVER THE SUMMER NOW HAD
THE SURMOUNT OSA STUDY, WHICH
WAS A TRIAL EVALUATING
TIRZEPATITDE, THIS DUAL AGONIST,
ON OBSTRUCTIVE SLEEP APNEA.
AND WHAT WAS OBSERVED WAS THAT
AT 52 WEEKS, A DOSE OF BETWEEN
10 AND 15 MILLIGRAMS OF
TIRZEPATITDE RESULTED IN A 16 TO
70% WEIGHT REDUCTION WHICH
TRANSLATE NEIGHBORHOOD A 20 TO
24% REDUCTION IN ACTIVE
HYPOPNEA.
THERE WERE ADDITIONAL BENEFIT
AND A VARIETY OF SECONDARY END
POINT INCLUDING CRP AND HYPOXIC
BURDEN AND BLOOD PRESSURE, BOTH
SYSTOLIC AND DIASTOLIC.
AND ALTHOUGH THIS MAY NOT BE A
THERAPY THAT CAN CURE PATIENTS
WITH RESPECT TO THEIR SLEEP
APNEA, I THINK THIS LEVEL OF
WEIGHT LOSS COULD BE AN
IMPORTANT ADJUNCTIVE TREATMENT
AND PERHAPS EXPAND SOME OF THE
POPULATIONS THAT MAY BENEFIT
FROM EITHER ORAL APPLIANCE
THERAPY OR HYPOGLOSSAL NERVE
STIMULATION.
I'M GOING TO SHIFT GEARS FOR
JUST A MOMENT AND TALK ABOUT A
DIFFERENT METABOLIC MODULATOR,
ANOTHER BLO BLOCKBUSTER DRUG IN
METABOLISM AND ENDOCRINOLOGY
WHICH ARE THE SGLT 2I
INHIBITORS.
SGLT 2I IS A RECEPTOR BASED IN
THE PROXIMAL TUBULE THAT IS
RESPONSIBLE FOR ABOUT 90% OF THE
GLUCOSE THAT IS FILTERED THROUGH
THE GL GLOMERULUS, AND THESE
INHIBITORS BLOCK THIS AND THUS
WE HAVE GLUCOSE UREA AND WE PEE
OUT ALL OF THIS GLUCOSE, AND
WITH THAT GLUCOSE EXCRETION,
THERE IS A MODEST WEIGHT LOSS OF
ABOUT A 300-CALORIE A DAY LOSS
ASSOCIATED WITH THIS GLUCOSE
EXCRETION.
THOUGH THESE DRUGS WERE
INITIALLY BROUGHT TO MARKET FOR
THE TREATMENT OF DIABETES, WE
HAVE SINCE LEARNED SIMILAR TO
THE GLP1s THAT WE'VE RECENTLY
LEARNED, THEY HAVE REALLY
IMPRESSIVE EFFECTS ON MAJOR
ADVERSE CARDIOVASCULAR EVENTS,
ON CARDIOVASCULAR DEATH, ON
HEART FAILURE AND EVEN KIDNEY
END POINTS.
I HAD THE OPPORTUNITY TO WORK
WITH FOLKS AND GO BACK AND LOOK
AT SOME OF THE CARDIOVASCULAR
TRIALS FOR THESE SGLT TWOs,
AND WE WENT BACK AND WE OBSERVED
QUITE CONSISTENTLY IN TWO
SEPARATE TRIALS USING TWO
SEPARATE DRUGS THAT THESE ALSO
HALF THE INCIDENCE FOR SLEEP
APNEA, AS AN ADVERSE OUT COME IN
THESE TRIALS.
AND WE HAVE NOW STARTED A TRIAL
TRYING TO FIGURE OUT HOW THESE
DRUGS MIGHT ACTUALLY IMPACT AND
SERVE AS A POTENTIAL TREATMENT
FOR SLEEP APNEA.
AND IN DOING THESE KINDS OF
MECHANISTIC TRIALS, WE CAN NOW
LEVERAGE SOME OF THE TOOLS, SO
IMAGING STUDIES, RICK SCHWAB IS
WORKING WITH US ON THIS TRIAL TO
LOOK AT USING MRI AND DYNAMIC
IMAGING TO LOOK AT HOW THESE
DRUGS MAY IMPACT ANATOMY, WEIGHT
LOSS IN THE UPPER AIRWAY, AND WE
ARE MEASURING THESE NON-ANATOMIC
PHYSIOLOGIC TRAITS TO SEE HOW
THESE DRUGS MAY IMPROVE AND
SERVE AS A TREATMENT OF
OBSTRUCTIVE SLEEP APNEA.
I'M GOING TO MOVE NEXT NOW TO
TALK ABOUT NOR ADRENERGIC AND
ANTIMUSCARINICS ON UPPER AIRWAY
MUSCLES.
WE NOW KNOW THAT THE SLEEP
RELATED WITHDRAWAL OF NOR
ADRENERGIC DRIVE IS A
SIGNIFICANT CAUSE OF
GENIOGLOSSUS HYPOTONIA,
PARTICULARLY DURING NON-REM
SLEEP, AND CORRESPONDINGLY,
ACTIVE MUSCARINIC INHIBITION
APPEARS TO REALLY MEDIATE THE
PHARYNGEAL HYPOTONIA,
PARTICULARLY DURING REM SLEEP.
AND WE SORT OF LEVERAGED THIS
INFORMATION AND NOW A NUMBER OF
RANDOMIZED CONTROL TRIALS
LOOKING AT COMBINATIONS OF NOR
ADRENERGIC AND ANTIMUSCARINIC
AGENTS, WHETHER THEY WOULD BE
HELPFUL IN TREATING OBSTRUCTIVE
SLEEP APNEA AND LO AND BEHOLD,
IN META-ANALYSIS OF THESE
TRIALS, THEY ARE.
AND THE EFFICACY HAS VARIED FROM
ONE STUDY TO ANOTHER, THE WORK
BY THE HARVARD GROUP, ONE OF THE
INITIAL STUDIES PUBLISHED, A
REALLY IMPRESSIVE 23-POINT
REDUCTION IN THE APNEA HIGH INDN
AVERAGE THERE'S ABOUT A 9 TO 10
UNIT REDUCTION, BUT ONE OF THE
THINGS THAT MAY EXPLAIN SOME OF
THE VARIABILITY, AND THIS WAS
ALSO IN THE META-ANALYSIS, IS
THAT MEN APPEAR TO RESPOND TO A
GREATER LEVEL THAN WOMEN.
AND WHAT WE SEE IN THIS FIGURE
IS THAT STUDYS THAT HAVE A
HIGHER PROPORTION OF MEN
RESULTED IN A SIGNIFICANTLY
LOWER DECREASE IN THE
APNEA/HYPOPNEA INDEX.
THIS IS ONE OF THE FIRST STUDIES
TO LOOK USING THE COMBINATION OF
ATOMOXETINE AND OXYBUTYNIN, AND
IT WAS REALLY THE COMBINATION OF
THESE TWO MEDICATIONS THAT LED
TO A SIGNIFICANT DECREASE AND
THEY MEASURED SOME OF THESE
TRAITS, IT WAS THROUGH THESE
PHYSIOLOGIC TRAITS AND IT WAS
THROUGH IMPROVEMENT IN
GENIOGLOSSUS ACTIVITY THAT THESE
WERE MEDIATED.
I'M GOING TO SHIFT NOW TO
HYPNOTICS, AND SOME OF THE DATA
ON THEIR IMPACT ON AROUSAL
THRESHOLD.
AND WHAT WE KNOW, AND AGAIN,
THESE ARE BASED ON NOW
META-ANALYSIS, THERE HAVE BEEN
SO MANY TRIALS NOW LOOKING AT
THE IMPACT OF HYPNOTICS ON
AROUSAL THRESHOLDS, AND THESE
DRUGS ARE CAPABLE OF RAISING THE
AROUSAL THRESHOLD, MAKING IT
HARDER TO WAKE UP DURING SLEEP.
BUT UNLIKE SOME OF THE OTHER
TRAITS SUCH AS THE GENIOGLOSSUS
AND SOME OF THE ANATOMIC, A
MODIFYING THE AROUSAL THRESHOLD
DIDN'T REALLY RESULT IN AN
OVERALL CLINICALLY SIGNIFICANT
IMPROVEMENT.
VERY, VERY MODEST.
WHAT WAS TO ME ACTUALLY QUITE
SURPRISING AND A LITTLE BITTEN
COURAGING WAS THE FACT THAT
THESE DRUGS ALSO DID NOT APPEAR
TO SIGNIFICANTLY IMPAIR
GENIOGLOSSUS FUNCTION.
LOOKING AT STUDIES THAT INCLUDED
TA MAT TTEMAZEPAM.
SO THESE HYPNOTICS DO NOT
SIGNIFICANTLY DECREASE
GENIOGLOSSUS ACTIVITY.
THOUGH THESE ARE NOT NECESSARILY
TREATMENTS TO IMPROVE THE
OVERALL APNEA HYPOPNEA INDEX,
OUR GROUP, I THINK, HAS BEEN
VERY INTERESTED IN HOW THESE
DRUGS MAY HELP IN TERMS OF
PROGNOSIS.
THIS IS WORK, THE LEAD AUTHOR IN
THE STUDY WAS ANDRE ZINSHA.
WHEN WE WENT BACK AND LOOKED AT
THE DATA FROM THE RIKADZA STUDY,
WE WERE STUNNED TO SEE THAT
THOSE PATIENTS WHO HAD LOW
AROUSAL THRESHOLD HAD NEARLY --
ALMOST A TWO-HOUR DIFFERENCE IN
THEIR ABILITY TO WEAR AND ADHERE
TO CPAP THERAPY.
SO KNOWLEDGE OF THIS ENDO DINO
TYPIC PHYSIOLOGIC TRAIT MAY BE
HELPFUL IN EXPLAINING CPAP
ADHERENCE AND CHOOSING THIS
THERAPY FOR INDIVIDUALS.
AND PERHAPS STUDIES THAT TARGET
THIS MAY MAKE IT EASIER FOR
PATIENTS TO ADHERE.
THIS IS WORK BY KRISTINE W. ON
FROM OUR GROUP AND I THINK HAS
BEEN MENTIONED BEFORE, WHO USING
THE MESA COHORT DEMONSTRATED IN
ADDITION TO LOWER LOOP GAIN,
LESS AIRWAY COLLAPSABILITY,
WOMEN CONSISTENTLY APPEAR TO
HAVE THIS LOWER' ROW SAL
THRESHOLD TRAIT.
IN FACT, THESE ENDOTYPES EXPLAIN
30% OF THE DIFFERENCES IN THEIR
NON-REM AHI.
THERE'S JUST A LOT OF INTEREST
ABOUT WHETHER THIS MAY EXPLAIN
WHY WOMEN MAY BE MORE LIKELY, I
THINK AS SUSAN BROUGHT UP
YESTERDAY, TO HAVE COMISA, AND
PERHAPS EXPLAIN SOME OF THE
LOWER ADHERENCE RATES TO CPAP
THERAPY.
WHICH IS INCREDIBLY IMPORTANT
GIVEN THEIR HIGH CARDIOVASCULAR
RISK FROM OBSTRUCTIVE SLEEP
APNEA.
THIS IS JUST TO REMIND US THAT
THE APPLE STUDY, WHICH WAS ONE
OF THE FIRST RANDOMIZED
CONTROLLED TRIALS IN OUR FIELD
LOOKING AT C PAM THERAPY WHICH
FOCUSED ON NEUROCOGNITION, AND I
THINK WE HAD A ROBUST DISCUSSION
OF THE IMPACT OF CPAP ON COG NI
REALLY SHOWED VERY MILD AND
TRANSIENT IMPROVEMENTS
PARTICULARLY IN EXECUTIVE
FUNCTION, WHICH WAS SORT OF
SURPRISING TO MANY OF US.
MORE RECENTLY, WE'VE GONE BACK
AND LOOKED AT THE APPLES DATA,
AND AS OBSERVED THAT THIS
EXECUTIVE FUNCTION IS COMPLETELY
MODIFIED BY THE AROUSAL
THRESHOLD.
SO THE PATIENTS WHO REALLY
BENEFIT FROM CPAP THERAPY WITH
RESPECT TO THIS MEASURE OF
COGNITION, EXECUTIVE FUNCTION
AND WE VALIDATED THIS IN TWO
SEPARATE MEASURES OF EXECUTIVE
FUNCTION, ARE THE ONES THAT HAVE
HIGHER AROUSAL THRESHOLD, THE
PATIENTS WITH LOWER AROUSAL
THRESHOLD DON'T SEEM TO BENEFIT.
SO WE WERE HEARING THOSE HEAR HE
PATIENTS TOGETHER AND THIS MAY
SHED SOME LIGHT ON HOW FUTURE
TRIALS AND HOW WE TARGET LOOKING
AT THINGS LIKE COGNITION.
ESRA'S JUST LAST TALK I THINK
BROUGHT UP CIRCADIAN BIOLOGY,
AND THAT'S NOT REALLY A FOCUS OF
THIS, BUT JUST TO POINT OUT THAT
A CIRCADIAN BIOLOGY DOES, IN
FACT, IMPACT SLEEP APNEA
TREATMENT AND WE CAN OFTEN MOD
MODIFY THAT WITH MEDICAL AND
BEHAVIORAL THERAPY.
MILY IS A KNAUERT IN OUR GROUP
ELEGANTLY WENT BACK THROUGH THE
APPLES DATA AND OBSERVED THAT
THOSE PATIENTS WHO WERE A
MORNING CHRONOTYPE HAD
SIGNIFICANTLY HIGHER ADHERENCE
RATES, SO ANOTHER DOMAIN TO
EXPLORE.
I'M GOING TO FINISH UP BY
TALKING ABOUT SOME OF THE DATA
ON CARBONIC AN HIGH DRAIS
INHIBITORS AND VENTILATORY
INSTABILITY AND WE WERE VERY
FORTUNATE THAT DR. SCHMICKL FROM
UCSD DID A VERY NICE AND
THOROUGH SYSTEMATIC LITERATURE
REVIEW ON THESE TOPICS.
SO THESE DRUGS BASICALLY ACIDIFY
THE BLOOD AND ARE TARGETING THE
LOOP GAIN, THE VENTILATORY
CONTROL INSTABILITY.
HE LOOKED AT POOLED STUDIES THAT
WERE LOOKING AT BOTH OBSTRUCTIVE
SLEEP APNEA AS WELL AS CENTRAL
SLEEP APNEA, AND THESE DRUGS
WORK.
THEY OVERALL LOWERED THE APNEA
HRB HYPOPNEA MIX BY A MEAN
DIFFERENCE OF 14 EVENTS PER
HOUR, ABOUT A 37% REDUCTION IN
SEVERITY.
WHAT SURPRISED ME, VERY SIMILAR
EFFICACY FROM BOTH OBSTRUCTIVE
AND CENTRAL SLEEP APNEA, I THINK
WE TEND TO USE THESE DRUGS MORE
CLINICALLY AMONG PATIENTS WITH
CENTRAL SLEEP APNEA, BUT IT
POINTS OUT THAT HIGH LOOP GAIN
OR VENTILATORY CONTROL
INSTABILITY IS PATHOPHYSIOLOGIC
AND OBSTRUCTIVE AS WELL AS
SENTRA SLEEP APNEA, AND THESE
DRUGS AS EXPECTED IN THEIR
DIURETIC CAPACITY WERE ALSO
FOUND TO SIGNIFICANTLY LOWER
BLOOD PRESSURE.
SO JUST BY WAY OF TAKE-HOME
POINTS AND WHAT WE'VE TALKED
ABOUT TODAY, KNOWLEDGE OF THESE
PHYSIOLOGIC TRAITS HAVE EXPANDED
OUR CONCEPT OF OSA PATHOGENESIS,
GLP-1 AGONISTS ARE COMBINATION
AGONISTS RESULT IN SIGNIFICANT
WEIGHT LOSS AND MARKED
IMPROVEMENT IN THE
APNEA/HYPOPNEA MIX FROM THE
SURMOUNT OSA TRIAL.
THE USE OF CLINICAL IMAGING
MODALITIES SUCH AS THE WORK FROM
PENICILLIN AND RICK SCHWAB
COMBINED WITH MEASURES OF
ENDOPHENOTYPES REALLY PERMIT
THESE SORT OF MECHANISTIC
CLINICAL TRIALS.
EXAMINING POTENTIALLY NOVEL
PHARMACOLOGIC TREATMENTS.
AND WE'RE LEVERAGING BOTH OF
THESE TOOLS IN ADIPOSA, THIS
SGL2 TRIAL, THAT WAS DONE AS
WELL AND SOME OF THE STUDIES
LOOKING AT GENIOGLOSSUS FUNCTION
AND
NEUROADRENERGIC/ANTIMUSCARINICS.
THIS COMBINATION OF NOR
ADRENERGIC AND ANTIMUSCARINIC
HAVE A MORE ROBUST EFFECT AMONG
MEN WITH RESPECT TO GENIOGLOSSIC
ACTIVITIES.
WE TALKED ABOUT HYPNOTICS ARE
ABLE TO ARROW THE THRESHOLD BUT
THEIR OVERALL IMPACT ON OSA
SEVERITY IS NOT THAT LARGE.
HOWEVER, THIS TOOL MAY ACTUALLY
END UP BEING MORE HELPFUL FROM
ITS PROGNOSTIC IMPLICATIONS.
IT'S ABLE TO PREDICT LOW CPAP
ADHERENCE, AND TARGETING THIS
MAY BE A THERAPEUTIC OPTION.
THERE HAVE BEEN SOME STUDIES
USING Z DRUGS THAT HAVE SHOWN
IMPROVED ADHERENCE RATES WITH
THE COMBINATION OF CPAP INSTEAD
OF HYPNOTICS.
THIS MEASURE OF AROUSAL
THRESHOLD, I THINK AS WE'VE
DISCUSSED ALREADY, MAY PROVIDE
REALLY IMPORTANT INSIGHT INTO
SOME OF THE SEX DIFFERENCES IN
SLEEP APNEA.
AND AS WE TALKED ABOUT, THIS
APPEARS TO MODERATE SOME OF THE
IMPACT OF CPAP ON EXECUTIVE
FUNCTION.
AND FINALLY, WE TALKED ABOUT HOW
ACETAZOLAMIDE LOWERS AHI BY 37%,
A SIMILAR IMPACT ON OBSTRUCTIVE
AND CENTRAL, AND IT APPEARS
BASED ON THAT META-ANALYSIS,
GREATER THAN 500 MG DOSE IS
REQUIRED TO REALLY SEE THESE
BENEFITS.
FINALLY, I THINK IN TERMS OF A
FUTURE OPPORTUNITIES, I THINK
THERE'S SOME REAL OPPORTUNITY
PERHAPS WITH THE SURMOUNT OSA
STUDY TO LOOK AT AND EXPLORE IN
MORE DETAIL SOME OF THE SEX
DIFFERENCES IN SLEEP APNEA THAT
OCCUR WITH GLP-1 FACILITATED
WEIGHT LOSS.
I THINK IT'S IMPORTANT FOR US TO
THINK BOTH ABOUT NOT JUST THE
OBJECTIVE POLYSONOGRAPHIC
MEASURES BUT THE SUBJECTIVE
MEASURES, SLEEPINESS, SYMPTOMS,
QUALITY OF LIFE, ET CETERA.
WE TALKED ABOUT -- AND I THINK
ANOTHER OPPORTUNITY IS USING
THIS COMBINATION OF IMAGING
MODALITIES AND THESE COMBINED
WITH MEASURES OF ENDO PHENOTYPES
TO REALLY BETTER UNDERSTAND SOME
OF THE SEX DIFFERENCES IN SLEEP
APNEA ACROSS VARIOUS LIFESPAN
STATES.
THAT INCLUDES PREGNANCY,
PREMENOPAUSAL STATUS AND
POST-MENOPAUSAL STATUS.
LONGER TERM FOLLOW-UP STUDIES IN
BOTH SEXES ARE NEEDED,
PARTICULARLY WITH RESPECT TO
ACETO TAZOLAMIDE, SEX DIFFERENCS
IN CIRCADIAN BIOLOGY.
I THINK THERE'S A REAL
OPPORTUNITY TO THINK ABOUT HOW
WE MIGHT COMBINE SOME OF THESE
PHARMACOTHERAPIES TO TARGET
SPECIFIC ENDOPHENOTYPES.
PATIENT DON'T USUALLY HAVE ONE
OF THESE BUT RATHER SOME OF THEM
TRACK TOGETHER, AND JUST LAST
PLUG, ON A COMPLETELY UNRELATED
TOPIC ON CANNABIS, AND AS I WAS
GOING THROUGH THIS LITERATURE ON
PHARMACOLOGY, THERE IS ACTUALLY
A LITERATURE ON LEVERAGING THE
ENDOCANNABINOID SYSTEM AND
CANNABIS IN TREATING OBSTRUCTIVE
SLEEP APNEA.
THIS IS NASCENT, BUT MORE FROM A
PUBLIC HEALTH -- I'VE RECENTLY
LEARNED AGAIN THIS SPEAKS TO
HETEROGENEITY BUT THAT THE
LARGEST RISING GROUP OF CANNABIS
USERS ARE OVER THE AGE OF 65,
THEY'RE USING IT FOR SLEEP AND
TO TREAT PAIN AND ALL OF THE
STUDIES HAVE BEEN DONE FROM THE
1970s IN YOUNG PEOPLE.
WE HAVE ZERO DATA AMONG OLDER
PEOPLE, AND I THINK THAT'S
REALLY IMPORTANT GIVEN HOW
LEGALIZATION HAS IMPACTED USE
ACROSS THIS COUNTRY.
SO WITH THAT, I'M GOING TO STOP.
THANK YOU VERY MUCH FOR YOUR
ATTENTION.
>> OKAY, DR. YAGGI, THANK YOU.
THAT WAS REALLY AN EXCEPTIONAL
OVERVIEW OF DIFFERENT
PHARMACOLOGICAL APPROACHES, FOR
TREATING SLEEP APNEA, AND THE
POTENTIAL FOR PERSONALIZING
THESE APPROACHES BASED ON THE
SPECIFIC PATHOBIOLOGY AND
SPECIFIC PHENOTYPES THAT THE
INDIVIDUALS MAY EXHIBIT.
I'D LIKE TO LEAVE TIME FOR ONE
QUESTION, EVEN THOUGH WE'RE
MOSTLY OUT OF TIME, BUT THIS IS
ONE THAT SHOWED UP IN THE CHAT.
SO IT SAYS DO YOU THINK SEX
DIFFERENCES IN VISCERAL FAT OR
OTHER FAT CHARACTERISTICS MAY
EXPLAIN SEX DIFFERENCE AND
WEIGHT LOSS IN RESPONSE TO
GLPs, AND IS IT PLAUSIBLE THAT
WE WILL SEE A BETTER OSA
RESPONSE WITH THOSE DRUGS IN
WOMEN DUE TO DIFFERENCES IN FAT
IN MEN AND WOMEN?
>> I THINK THAT'S AN EXCELLENT
QUESTION, AND WE TOUCHED A
LITTLE BIT UPON THIS YESTERDAY.
I THINK AT LEAST IN THE CHAT.
THERE WAS I THINK A VERY GOOD
DISCUSSION YESTERDAY ABOUT THE
IMPACT OF MENOPAUSAL STATUS ON
FAT DISTRIBUTION IN WOMEN.
AND THAT MAY AT LEAST IN PART
EXPLAIN HOW SLEEP APNEA IS
REALLY -- I THINK IT GOES UP
FOUR FOLD IF I REMEMBER
CORRECTLY COMPARING
PREMENOPAUSAL TO MENOPAUSAL
WOMEN.
AND THAT'S CERTAINLY, I THINK,
LIKELY A CONTRIBUTOR.
AND SO ALTHOUGH I THINK MANY
STUDIES HAVE SHOWN A MORE ROBUST
SLEEP APNEA IMPROVEMENT
ASSOCIATED WITH WEIGHT LOSS IN
GENERAL AMONG MEN, I'M NOT SURE
THEY HAVE BEEN STRATIFYING AND
LOOKING AT MENOPAUSAL STATUS IN
THAT.
AND I THINK IT'S AN EXCELLENT
HYPOTHESIS TO EXPLORE, AND WITH
SOME OF THESE TRIALS
PARTICULARLY WITH THIS DEGREE OF
WEIGHT LOSS, WE'LL HAVE AN
OPPORTUNITY.
AS A SIDE EMAIL JUST THIS WEEK,
THEY HAVEN'T RELEASED THAT YET
BUT I THINK THEY'RE UNDER FDA
RESTRICTIONS AT THE MOMENT BUT
HE SAID THAT'S ON THEIR RADAR
AND THEY'RE VERY MUCH INTERESTED
IN LOOKING AT THESE SEX
DIFFERENCES AT LEAST IN THE
SURMOUNT OSA TRIAL.
>> THANK YOU VERY MUCH.
IT'S TIME TO MOVE ON TO THE NEXT
SESSION.
SO I'D LIKE TO INTRODUCE THE
MODERATOR FOR SESSION FIVE,
DR. MEGHAN O'NEILL, SO MEGHAN,
WE'LL TURN THIS OVER TO YOU NOW.
>> GREAT.
THANK YOU SO MUCH.
ALL RIGHT.
SO GOOD AFTERNOON, EVERYONE.
MY NAME IS MEGHAN O'NEILL AND
I'LL BE MODERATING SESSION FIVE
TIETD TITHE HE WOULD WHAT CAN WE
LEARN ABOUT OSA HETEROGENEITY IN
PERSONS LIVING WITH INTELLECTUAL
AND DEVELOPMENTAL DISABILITIES?
I THINK I MIGHT BE THE ONLY NEW
MODERATOR TODAY SO JUST TO
INTRODUCE MYSELF QUICKLY, I AM A
MEDICAL OFFICER AT NICHD OR THE
EUNICE KENNEDY SHRIVER NATIONAL
INSTITUTE OF CHILD HEALTH AND
HUMAN DEVELOPMENT, AND I WORK IN
THE INTELLECTUAL AND
DEVELOPMENTAL DISABILITIES
BRANCH.
I'M TRAINED AS A PHYSICIAN IN
CHILD NEUROLOGY AND
NEURODEVELOPMENTAL DISABILITIES,
AND I MANAGE A PORTFOLIO OF
GRANTS RELEVANT TO IDD WITH
PARTICULAR INTEREST IN DOWN
SYNDROME.
IN THAT CAPACITY, I ALSO SERVE
ON THE INCLUDE PROJECT
LEADERSHIP TEAM AND I WANTED TO
TALK BRIEFLY ABOUT INCLUDE
BECAUSE IT'S RELEVANT TO OUR
TALKS TODAY.
THE INCLUDE ACRONYM STANDS FOR
INVESTIGATION OF CO-OCCURRING
CONDITIONS ACROSS THE LIFESPAN
TO UNDERSTAND DOWN SYNDROME.
WHICH IS A MOUTHFUL, BUT IT DOES
REPRESENT WELL WHAT OUR PROJECT
DOES.
THIS PROJECT WAS LAUNCHED IN
2018 IN SUPPORT OF A
CONGRESSIONAL DIRECTIVE FOR AN
NIH-WIDE INITIATIVE TO FUND MORE
RESEARCH TO ADDRESS CRITICAL
HEALTH AND QUALITY OF LIFE NEEDS
FOR INDIVIDUALS WITH DOWN
SYNDROME.
MOST OF YOU ARE AWARE THAT
OBSTRUCTIVE SLEEP APNEA AND
OTHER SLEEP DYSFUNCTION ARE ALL
STROOSTROODZLY COMMON IN PEOPLEH
DOWN SYNDROME SO MANY OF OUR
FUNDED INVESTIGATORS OVER THE
PAST SIX YEARS HAVE RESEARCHED
SLEEP IN DOWN DOWN SYNDROME ANT
INCLUDES THE TWO SPEAKERS WE'LL
BE HEARING FROM IN TODAY'S
SESSION.
OUR FIRST SPEAKER IS DR. CHRIS
CIELO, PROFESSOR OF PEDIATRICS
IN THE DIVISION OF PULMONARY AND
SLEEP MEDICINE AT CHILDREN'S
HOSPITAL OF PHILADELPHIA.
HIS PRESENTATION IS TITLED
LESSONS ABOUT OSA HETEROGENEITY
FROM A DOWN SYNDROME POPULATION.
AND WE'LL HAVE CHRIS TAKE OVER.
THANK YOU.
>> THANKS VERY MUCH, MEGHAN.
IS EVERYONE SEEING THE SLIDES?
>> WH YES, WE CAN SEE IT.
>> I'LL START OFF BY SAYING FOR
MANY YEARS AND STILL TO SOME
EXTENT, PEDIATRIC SLEEP APNEA
COHORTS HAVE BEEN RESTRICTED TO
EXCLUDE PATIENTS WITH GENETIC
CONDITIONS AND OTHER
COMORBIDITIES THAT REALLY
CREATES I THINK KIND OF THE
SPIRIT IN THIS WHOLE SESSION AN
ARTIFICIALLY HOMOGENEOUS COHORT
THAT'S REALLY NOT REPRESENTATIVE
OF THE PATIENTS THAT WE SEE IN
CLINIC AND IN THE REAL WORLD.
SO FOR THE NEXT FEW MINUTES I'LL
TALK A LITTLE ABOUT ONE
CONDITION, DOWN SYNDROME, AND
DR. O'NEILL ALREADY MENTIONED A
LITTLE BIT, HOPEFULLY CON VIPS
YOU THERE'S REAL VALUE IN
INCLUDES THESE PATIENTS AND
THOSE WITH SIMILAR CONDITIONS
ARE WORTH INCLUDING IN KRIN CALL
TRIALS AND OTHER STUDIES, I
THINK IT CAN BENEFIT THE
COMMUNITY OF PATIENTS WHO WE
SERVE AS WELL AS THE
INVESTIGATORS AND CLINICIANS.
JUST WANT TO POINT OUT FUNDING
AGENCIES LIKE NIH AND OTHERS
HAVE REALLY PUT REAL RESOURCES
IN IMPROVING THE HEALTH OF
PEOPLE WITH DOWN SYNDROME AND
SLEEP HAS BEEN A SIGNIFICANT
COMPONENT OF THAT INVESTMENT
PARTICULARLY THROUGH THE NIH
INCLUDE PROGRAM THAT SHE JUST
MENTIONED.
I'VE BEEN FORTUNATE THAT
MARISHKA, ALFONSO AND OTHERS
HAVE BEEN REAL ADVOCATES FOR
THIS KIND OF WORK TO GET SLEEP
IN PART OF THAT INITIATIVE.
I'VE HAD THE OPPORTUNITY TO
PARTICIPATE IN IN A NUMBER OF
STUDIES IN THIS AREA.
YOU CAN SEE FROM THIS LIST SOME
HAVE BEEN EARLY STAGE PILOT
STUDY, SINGLE CENTER CLINICAL
TRIALS LIKE THE ONE I'M DOING AT
CHOP CURRENTLY, THEN SOME OTHER
CLINICAL TRIALS, OTHER
MULTICENTER TRIALS, AND
U01 PROJECTS THAT HAVE RECENTLY
BEEN FUNDED THAT ARE GENERATING
LARGER STANDARDIZED DATA
COLLECTION NATIONALLY AND I
THINK GETTING SLEEP AND OTHER
METRICS INVOLVED WITH THOSE
COHORTS WILL REALLY BE A
VALUABLE RESOURCE MOVING FORWARD
FOR US AND FOR DOWN SYNDROME
INVESTIGATORS.
SO I'LL TALK ABOUT SOME OF THE
HETEROGENEITY IN THIS POPULATION
RELATED TO THE PRESENTATION OF
SLEEP APNEA, THE EVALUATION OF
OSA AND THEN MANAGEMENT OF SLEEP
APNEA AND AT THE END, I'LL JUST
TALK ABOUT SOME OF THE
OPPORTUNITIES AND CHALLENGES FOR
RESEARCHERS IN THIS AREA.
SO FOR THOSE WHO AREN'T FAMILIAR
WITH THIS CONDITION, DOWN
SYNDROME IS THE MOST COMMON
CHROMOSOMAL ABNORMALITY.
THERE'S ABOUT 400,000 PEOPLE
LIVING IN THE UNITED STATES
RIGHT NOW WITH DOWN SYNDROME
MOST OF WHICH HAVE A THIRD COPY
OF CHROMOSOME 21 BUT MORE RARELY
IT CAN OCCUR AS A MOSAIC OR
TRANSLOCATION, AND SOME OF THESE
CO-OCCURRING CONDITIONS THAT ARE
PART OF THIS INCLUDE INITIATIVE
RELATED TO SLEEP APNEA I THINK
ARE CRITICAL END POINTS OR
CONSEQUENCES OF SLEEP APNEA.
INTELLECTUAL DISABILITY IS ONE
OF THE HALLMARK FEATURES OF DOWN
SYNDROME AND THERE'S REALLY A
TREMENDOUS AMOUNT OF VARIABILITY
IN THAT OUT COME.
HEART DISEASE IS INCREDIBLY
COMMON, OVER HALF THE PEOPLE
WITH DOWN SYNDROME HAVE SOME
SORT OF CONGENITAL HEART
DISEASE.
THERE'S BEEN A LOT OF WORK
RECENTLY RELATED TO ALZHEIMER'S
DISEASE AND OBESITY IS
INCREASINGLY COMMON TOO, SO HOW
SLA RELATES TO SOME OF THESE
CO-OCCURRING CONDITIONS REALLY
IS JUST NOT WELL UNDERSTOOD BUT
THIS IS A VERY ENRICHED
POPULATION TO THINK ABOUT SOME
OF THOSE QUESTIONS.
THERE'S BEEN TREMENDOUS
IMPROVEMENT IN PATIENTS WITH
DODOWN SYNDROME.
IT'S AMAZING TO THINK THEIR LIFE
EXPECTANCY WAS ONLY 10 YEARS
BACK IN 1960 AND NOW CURRENTLY
MORE THAN 60 YEARS.
THERE WERE TREMENDOUS HEALTH
DISPARITIES IN THIS POPULATION
WITH WHITE PEOPLE WITH DOWN
SYNDROME WERE LIVING TWICE AS
LONG AS THOSE THAT WERE BLACK,
SO THERE'S A LOT OF HEALTH
DISPARITIES IN THIS POPULATION
AS WELL.
AND WHEN THINKING ABOUT SLEEP
APNEA, DOWN SYNDROME IS REALLY
SORT OF A PERFECT STORM.
YOU -- THIS HAS BEEN BROUGHT UP
SEVERAL TIMES IN OTHER TALKS
ABOUT SOME OF THESE MORE MORE
ANATOMIC FEATURES.
MACROGLOSSIA, NARROW, FLOPPY
AIRWAYS.
THESE PATIENTS IS HYPOTONIA AND
THEN OBESITY IS VERY COMMON AND
WE'RE SEEING MORE OF IT IN THIS
GROUP.
SO IT'S SOME REASONS WHY THERE'S
JUST A VERY, VERY HIGH
PREVALENCE OF SLEEP APNEA.
EVEN WITH ALL THAT, WE REALLY
DON'T KNOW EXACTLY WHAT THE
PREVALENCE ACTUALLY IS IN THIS
POPULATION, SORT OF ACROSS THE
LIFESPAN.
WE KNOW THAT IT'S VERY
PREVALENT, AND WE KNOW
APPROXIMATELY 50% OR MORE
CHILDREN WITH DOWN SYNDROME HAVE
SLEEP APNEA AND INFANTS MAY
ACTUALLY BE AT THE HIGHEST RISK.
THIS IS SOME WORK DONE BY KAREN
WATERS IN SYDNEY WHO LOOKED AT
152 CHILDREN ACROSS THE
PEDIATRIC -- SPECTRUM AND WE
REALLY DON'T SEE THIS IN MOST
OTHER POPULATIONS.
IN ADULTS, THE PREVALENCE AGAIN
NOT REALLY TOTALLY UNDERSTOOD
BECAUSE WE DON'T HAVE GOOD
POPULATION-BASED COHORTS BUT
THERE HAVE BEEN SOME COHORTS
WHERE 100% OF REFERRALS HAVE
BEEN FOUND TO HAVE SLEEP APNEA,
PEOPLE THINK THAT'S LIKELY IN
THE 78% RANGE AND A VERY HIGH
PROPORTION OF THOSE PATIENTS
HAVE SEVERE OSA.
THERE ARE HIGH RATES OF SLEEP
RELATED HYPOVENTILATION EVEN
REGARDLESS OF OSA SEVERITY.
THERE'S A SIGNIFICANT IMPACT
FROM SLEEP APNEA ON THESE
PATIENTS WHO ALREADY HAVE A LOT
OF CO-OCCURRING COMORBIDITIES.
THIS IS A FIGURE BY THE
BARCELONA GROUP WHICH SORT OF
HAD THIS HYPOTHESIZED
RELATIONSHIP BETWEEN BEHAVIORAL
SLEEP DISORDERS AND OBSTRUCTIVE
SLEEP APNEA KIND OF DISRUPTING
SLEEP, AND THEN CAUSING SORT OF
A WORSENING OF SOME OF THESE
HALLMARK FEATURES.
I THINK SOME OF THE DISCUSSION
THAT'S BEEN GOING ON THROUGHOUT
YESTERDAY AND TODAY'S SESSIONS
ABOUT SLEEP DISRUPTION,
INSUFFICIENT SLEEP, AND THEN
EVEN WHAT DR. YAGGIE WAS JUST
MENTIONING OR GOING THROUGH SOME
OTHER DATASETS TO TRY TO LOOK AT
DISRUPTION OF SLEEP MAY BE
REALLY RELEVANT HERE AND HAS NOT
BEEN EXPLORED IN PATIENTS WITH
DOWN SYNDROME.
WE KNOW IN KIDS, ESPECIALLY,
THERE'S A NEGATIVE CORRELATION
BETWEEN THE APNEA HYPOPNEA INDEX
AND THE DEVELOPMENTAL QUOTIENT.
THETHIS WAS A CROSS-SECTIONAL SY
OF 53 KIDS WHO UNDERWENT
DEVELOPMENTAL TESTING AND
POLYSONOGRAPHY, THERE'S A
CORRELATION BETWEEN THEIR AHI
AND DEVELOPMENTAL QUOTIENT.
BUT THE IMPACT OF SLEEP APNEA IN
INFANTS REALLY ISN'T WELL-KNOWN
AND WE KNOW THAT THIS GROUP OF
PATIENTS CAN HAVE SLEEP APNEA
FROM THE TIME THAT THER VERY
YOUNG.
SO CLEARLY A LOT MORE NEED TO BE
DONE IN THIS AREA.
SO THE HIGH PREVALENCE AND
POTENTIALLY SIGNIFICANT IMPACT
IN PEOPLE WITH DOWN SYNDROME
POSES SOME CHALLENGES FOR WHEN
AND THEN HOW TO EVALUATE THIS
POPULATION OF PEOPLE IN TERMS OF
SLEEP APNEA AND BECAUSE THERE'S
SUCH A HIGH RISK AND SCREENING
QUESTIONS ARE REALLY NOT
VALIDATED IN YOUNG KIDS, THE
AMERICAN ACADEMY OF PEDIATRICS
ACTUALLY HAS RECOMMENDED THAT
ALL PATIENTS WITH DISUNDERGO
POLYSO KNOWGRAPHY OR SLEEP APNEA
EVALUATION.
THEY JUST CHANGED THIS GUIDELINE
FROM FOUR TO 3 1/2 YEARS OLD.
AND THEY SAY THAT FOR CHILDREN
THAT ARE YOUNGER AND OLDER, THAT
WE SHOULD JUST USE SYMPTOMS,
ALTHOUGH UNFORTUNATELY THERE'S
NOT A LOT OF GOOD EVIDENCE
SAYING THAT THAT'S BEEN A
SUCCESSFUL STRATEGY.
IN THE UK, THEY ACTUALLY JUST
RECOMMEND OXIMETRY FOR INFANTS
AND THEN THROUGH AGE 3 TO 5, AND
YOU CAN SEE THIS WAS A REALLY
IMPORTANT STUDY DONE BY BRIAN
SKOTKO AND COLLEAGUES IN BOSTON
WHERE THEY ACTUALLY TOOK A LOT
OF TIME TO TRY TO VALIDATE A
DOWN SYNDROME SPECIFIC
QUESTIONNAIRE.
HE'SA REALLY INVESTED DOWN
SYNDROME RESEARCHER WHO'S REALLY
PARTNERED WITH A NUMBER OF OTHER
GROUPS SO THEN THEY ACTUALLY
WENT BACK AND TRIED TO VALIDATE
THIS AND THEY CREATED A NUMBER
OF DIFFERENT MODELS AND
UNFORTUNATELY THEY WERE REALLY
TERRIBLE AT PREDICTING THE
POSITIVE AND -- THE FALSE
POSITIVE AND TRUE POSITIVE RATE
FOR SLEEP APNEA IN THIS GROUP.
SO VERY HARD TO SCREEN THEM.
SO IT'S JUST SORT OF HARD TO
KNOW WHEN TO DO THE INITIAL
EVALUATION AND THEN WHEN TO DO A
FOLLOW-UP EVALUATION.
AND WE KNOW THAT IN GROUPS EVEN
WHO DON'T HAVE SYMPTOMS BOTH IN
CHILDREN AND IN ADULTS, THAT
VERY HIGH RATES OF THOSE
PATIENTS CAN STILL HAVE OSA.
SO IN ADDITION TO NOT HAVING
ADEQUATE SCREENING PROCEDURES,
THERE'S OTHER REASONS WHY
UNFORTUNATELY MANY PEOPLE WITH
DOWN SYNDROME AREN'T EVALUATED
FOR SLEEP APNEA AND A LOT OF
PLACES JUST REALLY AREN'T
APPROPRIATE FACILITIES.
WE SEE THIS ALL THE TIME AT
CHILDREN'S LOPTS LIKE WHERE I
WORK WHERE KIDS FOR YEARS HAVE
BEEN TRYING TO GET SLEEP STUDIES
AND THEY'RE NOT ABLE TO DO IT
EITHER BECAUSE FACILITIES WON'T
ACCEPT THEM, LABS WON'T ACCEPT
THEM OR THEY ATTEMPT IT AND THEN
THEY FAIL.
IT'S REALLY CHALLENGING.
POLYSONOGRAPHY MAY BE REALLY
DIFFICULT BECAUSE SOME OF THESE
KIDS HAVE SENSORY ISSUE, THEY
MAY HAVE FEAR OF GOING TO THE
HOSPITAL FOR LOTS OF MEDICAL
ISSUES THEY MAY HAVE, AND THERE
WAS A STUDY THAT CAME OUT OF
CINCINNATI CHILDREN'S WHICH WAS
REALLY ONE OF THE TOP CHILDREN'S
HOSPITALS IN THE COUNTRY WHERE
ONLY ABOUT 60% OF THE KIDS ARE
EVEN EVALUATED FOR SLEEP APNEA
AND THEY FOUND THAT DISTANCE
FROM THE HOSPITAL ACTUALLY
CORRELATED WITH WHETHER OR NOT
PATIENTS WERE BEING EVALUATED.
SO WE JUST REALLY DON'T
UNDERSTAND THE NATURAL HISTORY
OF SLEEP APNEA IN THIS
CONDITION.
AND THERE REALLY AREN'T DOWN
SYNDROME SPECIFIC GUIDELINES FOR
SLEEP APNEA IN OLDER ADULTS IN
TERMS OF WHETHER THEY SHOULD
HAVE INLAB POLYSONOGRAPHY, HOW
LONG THEY SHOULD BE SCREENED,
WHETHER HOME TESTING WOULD BE
APPROPRIATE, SO LOTS OF
IMPORTANT QUESTIONS THERE.
SO I'D LIKE TO HIGHLIGHT SOME OF
THE RECENT ANTIONGOING WORK TO
ADDRESS SOME OF THESE ISSUES
RELATED TO IMPROVING EVALUATION
AND MANAGEMENT IN CHURN AND
ADULTS WITH DOWN SYNDROME.
THIS IS SOME WORK THAT'S BEEN
GOING ON AT MY INSTITUTION THAT
WE'VE BEEN FORTUNATE TO PARTNER
WITH A LOT OF THESE FAMILIES,
AND WE KNOW THAT WE FOUND THAT
HOME SLEEP TESTING MAY BE AN
ALTERNATIVE IN CHILDREN WITH
DOWN SYNDROME THAT HAVE TROUBLE
EITHER ACCESSING SLEEP
LABORATORIES OR HAVING THE
TESTING COMPLETED, AND SO WE'VE
SEEN FOR YEARS THERE'S BEEN WORK
DONE BY BROCKMANN IN CHILE AND
THERE'S TESTING POSSIBLE IN KIDS
AND EVEN INFANTS WITH DOWN
SYNDROME.
WE DID THIS PILOT STUDY WHERE WE
FOUND THAT 43 YOUTH, MOSTLY
ADOLESCENTS BUT SOME SCHOOL AGED
KIDS AND SOME YOUNG ADULTS
ACTUALLY HIGHLY PREFERRED DOING
HOME SLEEP TESTING COMPARED WITH
IN-LAB POLYSOME NOGRAPHY.
WE FOUND HOME TESTS ACTUALLY HAD
PRETTY GOOD ACCURACY FOR OSA
COMPARED WITH IN-LAB PSG.
WE'RE CONTINUING WITH OUR
CURRENT CLINICAL TRIAL WHICH HAS
BEEN PRETTY SUCCESSFUL IN
RECRUITING BOTH KIDS WITH AND
WITHOUT DOWN SYNDROME TO TRY A
BETTER STUDY LIST WITH LARGER
NUMBERS OF PATIENTS.
THEN LOOKING IN TERMS OF
RESPONSE TO OSA TREATMENT, THIS
IS UNFORTUNATELY PRETTY HIGHLY
VARIABLE.
I'LL SHOW IN THE NEXT SLIDE A
NUMBER OF ONGOING STUDIES IN
THIS AREA.
SO THIS WAS SOME WORK IN THIS
TOP FIGURE BY A GROUP, FIRST
LINE THERAPY FOR CHILDREN WITH
OBSTRUCTIVE SLEEP APNEA.
UNFORTUNATELY ALMOST HALF HAD
RESIDUAL OHI GREATER THAN
5 WHICH IS CONSIDERED SUGGEST
CAN'T SLEEP SIGNIFICANT SLEEP A.
SO THERE'S A HIGHLY VARIABLE
RESPONSE MORE THAN WE WOULD
EXPECT TO SEE IN OTHERWISE
HEALTHY KIDS.
THIS IS SOME WORK DONE BY MY
COLLEAGUE LOOKING AT CPAP THAT
REALLY PERFORMED A LOT OF VERY
DETAILED SEMI STRUCTURED
INTERVIEWS AND PARENTS.
-- REALLY ASSOCIATED WITH
ADHERENCE, SO HER WORK RIGHT NOW
IS TRYING TO FOCUS IN SOME
ONGOING CLINICAL TRIALS OF HOW
TO USE SOME OF THOSE QUALITATIVE
FIND TOTION IMPROVE ADHERENCE
WITH CPAP AND OTHER MEASURES
LIKE NASAL CANNULA OXYGEN FOR
THESE FAMILIES.
THERE'S BEEN A LOT OF WORK DONE
WITH HYPOGLOSSAL NERVE
STIMULATION RELATED TO SLEEP
APNEA IN CHILDREN WITH DOWN
SYNDROME, ALL WITH PRETTY
VARIABLE RESULTS.
SOME KIDS DO VERY WELL BUT IN
THIS COHORT WHICH IS PUBLISHED
RECENTLY, THERE'S ABOUT A 50%
REDUCTION BUT AGAIN HIGHLY
VARIABLE AND ABOUT 36% HAD AN
AHI LESS THAN 5 AFTER ONE YEAR.
SO AGAIN THERE'S LOTS OF
PATIENTS WHO ARE SORT OF
UNDERTREATED SO MAY BE SOME
POSSIBILITIES FOR LEVERAGING
MULTIPLE DIFFERENT TREATMENTS AS
HAS BEEN MENTIONED IN OTHER
TALKS.
JUST TO COMMENT ON, THERE'S A
WHOLE BUNCH OF DIFFERENT TRIALS
HERE THAT ARE ONGOING RIGHT NOW,
I'M NOT GOING TO GO INTO A LOT
OF DETAIL HERE, BUT A LOT OF
THESE HAVE DIFFERENT OUTCOMES
THAT ARE BEING ECK AM INNED A EI
THINK HIS COMMENTS ABOUT
SEQUENTIAL THERAPIES ARE REALLY
RELEVANT TO THIS POPULATION
BECAUSE THERE'S JUST SUCH A HIGH
FAIL RATE, AND THERE COULD BE A
REALLY IMPORTANT GROUP TO LOOK
AT OF COMBINATION OF SEQUENTIAL
THERAPIES.
THIS IS DR. REDLINE'S TRIAL
LOOKING AT ME SAL CANNULA
OXYGEN, THE MOSAIC STUDY IS RUN
BY DAN COMBS IN ARIZONA AND IS
LOOKING AT A COMBINATION DRUG
THERAPY THAT HAS SOME PROMISE IN
CHILDREN.
THIS IS THE APAP21 TRIAL LOOKING
AT A MORE INTENSIVE CPAP
INTERVENTION.
AND THEN DERRICK LAM AT OREGON
LOOKING AT DRUG INDUCED SLEEP
ENDOSCOPY, I THINK WE'RE GOING
TO HEAR ABOUT SOME SELF
SUPPORTED NASOPHARYNGEAL AIRWAY
THAT INCLUDES SOME PEOPLE WITH
DOWN SYNDROME AS WELL.
SO A LOT OF EXCITING WORK GOING
ON IN THIS AREA.
I'LL JUST BRIEFLY MENTION TO
WRAP UP HERE THAT THERE'S A LOT
GOING ON IN TERMS OF JUST DATA
COLLECTION IN THIS AREA SO THE
INCLUDE INITIATIVE HAS FUND THIS
HAD DATA COORDINATING CENTER
WHICH INCLUDES A LOT OF
RESOURCES AND OUTREACH TO
DIFFERENT STUDY TEAMS, THINKING
ABOUT DATA COLLECTION AND
MANAGEMENT AND THEN THEY PROVIDE
TOOLS FOR DATA ANALYSIS AND
INTERPRETATION.
I'VE BEEN IN SOME CALLS WITH
LEADERSHIP FROM THIS GROUP AND
THEY'RE REALLY TRYING TO BE
THOUGHTFUL ABOUT ESPECIALLY SOME
OF THE MORE IMPORTANT
COMORBIDITIES.
YOU CAN SEE SLEEP APNEA IS IN
RED THERE, THE CONDITION FOR
WHICH THEY HAVE THE FIFTH MOST
PARTICIPANTS.
LIKE THERE'S ABOUT 1300 RIGHT
NOW, I KNOW THIS COHORT IS
GROWING, SO I THINK IT'S JUST
GENERATING AN IMPORTANT DATASET
THAT WE CAN KIND OF PARTNER WITH
A LOT OF THESE INVESTIGATORS
FOCUSED ON DOWN SYNDROME.
I MENTIONED NE BEGINNING THERE'S
THIS NEWLY FUNDED U01 PROGRAM
LOOKING FOR STANDARDIZED
COLLECTION ACROSS A NUMBER OF
SITES INCLUDING MY OWN AND I
THINK AGAIN WE'RE TRYING TO HAVE
SOME IMPORTANT SLEEP METRICS
COLLECTED THERE BOTH IN CHILDREN
AND IN ADULTS SO THAT WE CAN
HAVE THAT AS WELL AS ALL THE
OTHER COMORBIDITIES THAT WILL BE
COLLECTED WHICH I THINK WILL BE
A GREAT RESOURCE.
I THINK FINALLY I'LL MENTION
THAT THERE HAVE BEEN SOME
CHALLENGES BUT SOME REALLY GREAT
OPPORTUNITIES IN TERMS OF
PARTNERING WITH THIS COMMUNITY.
THESE PATIENTS CAN HAVE REALLY
VARIABLE INTELLECTUAL DISABILITY
WHICH MAKES IT PROPOSE SOME
CHALLENGES.
THERE CAN BE A LIMITED LOCAL
POPULATION, THERE'S A LOT OF
HETEROGENEITY AMONG THE
CO-OCCURRING CONDITION BUT
THERE'S A LOT OF I THINK VALUE,
THESE FAMILIES ARE REALLY
INVESTED IN THE RESEARCH,
THERE'S A HIGH INCLUSION AND
RETENTION RATE AND THERE'S A LOT
OF RESOURCES AVAILABLE TO THEM
TO PARTICIPATE IN RESEARCH.
SO OPPORTUNITIES INCLUDE
UTILIZING LARGE COHORTS THAT ARE
GETTING BIGGER AND BIGGER TO
ASSESS SOME OF TEASE
RELATIONSHIPS, COLLABORATING
BETWEEN INVESTIGATORS FOCUSED ON
DOWN SYNDROME AS WELL AS SLEEP
INVESTIGATORS LIKE THOSE ON THIS
CALL.
AND THEN CHARACTERIZING OSA
ACROSS THIS HIGH RISK POPULATION
ACROSS THE LIFESPAN.
SO THAT WILL BE IT FOR ME.
>> GREAT.
THANK YOU SO MUCH, DR. CIELO.
SO WE JUST HEARD A GREAT
DISCUSSION ABOUT THE HIGH RISK
OF OSA AMONG INDIVIDUALS WITH
DOWN SYNDROME, THE PRESENTATION
EVALUATION AND MANAGEMENT AND I
THINK HIGHLIGHTING THE NEED FOR
MORE -- JUST MORE INFORMATION
ABOUT THE NATURAL HISTORY OF OSA
IN DOWN SYNDROME AND THE
IMPORTANCE OF SEQUENTIAL
THERAPISTS AND SOME SORT OF
ALTERNATIVE TREATMENT OPTIONS.
AGO THOSE LINES, WE'RALONG THOSG
TO TRANSITION TO HEARING MORE
ABOUT EMERGING THERAPY FROM
DR. DAVID ZOPF, ASSOCIATE
PROFESSOR IN THE DIVISION OF
OTOLARYNGOLOGY, HEAD AND NECK
SURGERY AND THE DIRECTOR OF
INNOVATION AND SECTION CHIEF OF
PEDIATRIC -- AT THE UNIVERSITY
OF WISCONSIN SCHOOL OF MEDICINE
AND PUBLIC HEALTH.
HIS PRESENTATION IS TITLED
EMERGING OSA THERAPIES IN
VULNERABLE POPULATIONS.
THANK YOU.
>> HELLO.
THANK YOU SO MUCH.
REALLY EXCITED TO HAVE THE
OPPORTUNITY TO JOIN THIS REALLY
WONDERFUL DISCUSSION.
AS WAY OF DISCLOSURES, THESE ARE
LISTED BELOW, AND I'LL JUST
HIGHLIGHT THE TREMENDOUS SUPPORT
AND COLLABORATION WITH
DR. ALFINI, DR. BROWN AND NHLBI.
SO WHAT WE'RE GOING TO DO IS
KIND OF LOOK AT A COUPLE OF
VULNERABLE POPULATIONS,
PARTICULARLY DOWN SYNDROME AND
CEREBRAL PALSY, AND REALLY KIND
OF HIGHLIGHT THE NEED FOR
ADDITIONAL TREATMENT OPTIONS
ACCESSIBLE TO ALL.
AND THE WAY THAT I'LL KIND OF
THINK ABOUT THESE TWO IS KIND OF
AN INDEX NON-SURGICAL INNOVATION
AND INDEX SURGICAL INNOVATION.
WE TALKED A LITTLE BIT ABOUT
DOWN SYNDROME, CEREBRAL PALSY AS
WE KNOW IS THE MOST COMMON
NEUROMUSCULAR DISABILITY IN
CHILDHOOD.
AND IT'S INTERESTING HOW THERE
ARE A NUMBER OF ANATOMIC AND I
THINK PHYSIOLOGIC PARALLELS WITH
DOWN SYNDROME AND WE'VE HEARD A
GOOD AMOUNT WITH SOME OF THE
UNDERLYING PREDISPOSITION
ANATOMIC CONTRIBUTORS FROM DOWN
SYNDROME AND WHAT I WAS FINDING
AS I WAS EVALUATING MORE AND
MORE PATIENTS WITH CEREBRAL
PALSY AND DOWN SYNDROME IS
THERE'S QUITE A BIT OF
SIMILARITY BETWEEN THE TWO WHERE
THERE'S A PREDOMINENCE OF KIND
OF RETRO PALATAL AND RETRO
LINGUAL COLLAPSE, AND THIS IS
JUST A NICE SAGITTAL PICTURE
SHOWING A NUMBER OF THOSE
ANATOMICAL CONTRIBUTORS BUT
CEREBRAL PALSY AS WELL.
I THOUGHT THIS WOULD BE GOOD
JUST TO KIND OF THINK THROUGH AS
A PEDIATRIC OTOLARYNGOLOGIST WHO
PARTICIPATES IN A
MULTIDISCIPLINARY SLEEP CLINIC,
HOW DO I THINK ABOUT KIND OF THE
CURRENT STATE OF TREATMENT
OPTIONS.
WITH THESE VULNERABLE PATIENT
POPULATIONS, IT'S GOING TO BE
LIKELY A MULTIMODAL
INDIVIDUALIZED TREATMENT
APPROACH.
AND WE KNOW SOME OF THE GOLD
STANDARD TREATMENTS ARE POSITIVE
AIRWAY PRESSURE, PERHAPS NASAL
OXYGEN, DRUG INDUCED SLEEP
ENDOSCOPY HAS BEEN A REALLY
VALUABLE TOOL, AND USING DISE
INDUCED UPPER AIRWAY SURGERY
MIGHT BE AN OPTION.
SO OPTIONS IN WHITE ARE REALLY
NON-SURGICAL APPROACHES AND THE
OPTIONS IN BLUE ARE SURGICAL
APPROACHES.
WE KNOW DENTAL APPLIANCES MAY BE
HELPFUL FOR MILD THOUGH MAY BE
LIMITED AS FAR AS VULNERABLE
POPULATIONS.
WE TALKED A GOOD AMOUNT THIS
MORNING ABOUT WEIGHT REDUCTION
STRATEGIES AND GLP,
PHARMACEUTICALS, AND THEN
POTENTIALLY AS THEIR ROLE FOR
BARIATRIC SURGERY AND MORE
MORBID OBESITY,
NASOCORTICOSTEROIDS OR ORAL
LEUKOTRIENE MODIFIERS.
TYPICALLY MUCH FURTHER DOWN THE
LIST FOR ME IS CONSIDERATION OF
HYPOGLOSSAL STIMULATOR OR
TRACHEOSTOMY, SO WE KNOW THAT --
UNFORTUNATELY ARE NOT AS
EFFECTIVE IN THE DOWN SYNDROME
AND CP POPULATION, AND
PARTICULARLY IN THE CP
POPULATION, PAP THERAPY CAN BE A
RISK, RIGHT, WITH ASPIRATION OR
POTENTIAL ASPHYXIATION RISK.
ADENOTONS ELTONS LEADENOTONSILLD
PATIENTS HAVE PERSISTENT OSA.
IN ADDITION, THESE POPULATIONS
NOT ONLY ARE THEY MUCH MORE
LIKELY TO FAIL TREATMENT WITH
THESE GOLD STANDARD TREATMENTS
BUT THEY'RE ALSO IN THE SURGICAL
OPTIONS MUCH HIGHER
PERIOPERATIVE RISKS, SO
PARTICULARLY THE CEREBRAL PALSY
POPULATION, WHEREAS OTHERWISE
HEALTHY CHILD HAVING
ADENOTONSILLECTOMY MAY GO HOME
NA DAY OR THE NEXT DAY, PATIENTS
WITH CEREBRAL PALSY MAY BE IN
THE ICU FOR THREE OFF FOUR WEEKS
AND HAVE PERIODIC COMPLICATIONS
REQUIRING REINTEGRATION SYNDROME
TO A LESSER EXTENT BUT ALSO MUCH
HIGHER PERIOPERATIVE RISK.
A GOOD NUMBER OF THEY WILL ENDED
UP GOING FORWARD AND REQUIRING
TRACHEOSTOMY TO ADDRESS THEIR
UPPER AIRWAY OBSTRUCTION.
SO I FOUND MYSELF REALLY KIND OF
STRUGGLINGERRING FAMILIES THAT
HAVE KIND OF REACHED THE POINT
WHERE THE OPTIONS ENDED UP BEING
TRACHEOSTOMY OR PALLIATIVE
OBSERVATION WAS REALLY
DISSATISFYING FOR THE FAMILIES
AND THE PATIENTS AND CERTAINLY
THE CAREGIVERS AS WELL, AND SO
WE REALLY WERE INSPIRED TO
DEVELOP SOMETHING NOVEL, KIND OF
IN BETWEEN.
AND SO I THOUGHT THROUGH THE
ANATOMIC PATTERN OF COLLAPSE AND
IT REMINDED ME OF PATIENTS WITH
ANOTHER POPULATION I CARE FOR
WHERE THERE IS A SIGNIFICANT
AMOUNT OF RETRO LINGUAL COLLA
COLLAPSE, BASAL TIME WAS KIND OF
THE STAR OF THE SHOW.
THE GREAT -- HAD LED THE WAY
WITH TREATING THOSE PATIENTS
WITH NAY SEWER FAIR JEEL
AIRWAYS.
SO THAT WAS KIND OF THE STARTING
POINT FOR OUR DESIGN AND I
THOUGHT IF WE COULD BYPASS THE
RETRO PALATAL AND RETRO LINGUAL
OBSTRUCTION, PERHAPS WE COULD DO
A GOOD JOB OF TREATING THIS
UPPER AIRWAY OBSTRUCTION.
THERE'S A NUMBER OF DESIGN
FEATURES TO THE DEVICE WHERE
IT'S ACTUALLY OPEN CHANNEL SO
IT'S MORE LIKE A NASOPHARYNGEAL
STENT.
THIS IS AN EXAMPLE OF AN ENDO
SCOPIC EXAM OF A PATIENT WITH
CHECKPOINT.
YOU CAN HEAR THE OBSTRUCTION.
THIS PATIENT IS AWAKE.
THIS IS NOT A SLEEP ENDOSCOPY.
THEY'RE AWAKE AND SO THERE'S
COMPLETE PALATAL OBSTRUCTION AND
YOU'LL SEE VERY DYNAMIC AND
SEVERE OBSTRUCTION BEHIND THE
TONGUE TOO.
BUT THE PATTERN I WAS SEEING
WAS, ONCE WE GOT BEYOND THAT
TONGUE, THE AIRWAY OPENS UP
REALLY NICELY, SO THERE'S NO
SUPERGLOTTIC COLLAPSE, THE VOCAL
CORDS ARE OPENING REALLY NICELY.
ONE OF THE COMMENTS THAT CAME
WAS, YOU KNOW, WHO'S GOING TO
TOLERATE ANYTHING GOING IN THEIR
NOSE AND INTERESTINGLY, THIS
DEVELOPMENT STARTED PREPANDEMIC,
AND SO IT WAS INTERESTING TO SEE
HOW MOST EVERYBODY HAD TO
UNDERGO SOMETHING GOING IN THEIR
NOSE WITH COVID TESTS BUT A LOT
OF DESIGN OF THE DEVICE HAS BEEN
FOCUSED ON MAKING IT COMFORTABLE
TO PLACE AND TOLERABLE.
THIS IS A VIDEO OF A PATIENT
WITH SEVERE CEREBRAL PALSY.
SO THE PARENT PROVIDED VIDEO AND
YOU CAN HEAR THE REALLY SEVERE
OBSTRUCTION.
REALLY KIND OF WORKING FOR EVERY
BREATH.
AND THEN MOTHER IS GOING TO
PLACE THE DEVICE.
>> IS THAT BETTER?
YEAH, YEAH!
>> SO YOU CAN HEAR THE
OBSTRUCTION HAS PRETTY QUKLY
QUIETED DOWN.
SO WE'RE VERY FORTUNATE TO BE
STARTING THE FOURTH YEAR OF OUR
R33 PHASE OF THIS RANDOMIZED
CONTROL CLINICAL TRIAL.
I REALLY LOVE THE DESIGN OF THE
TRIAL, AND IT'S RANDOMIZED
CONTROLLED SO HALF OF PATIENTS
ARE GOING TO BE WAIT LIST
CONTROLLED WITH THE IDEA THAT IF
A PATIENT GETS PRESCRIBED CPAP
OR GETS BOOKED FOR A SURGERY,
IT'S NOT GOING TO HAPPEN THAT
DAY, THERE'S LIKELY GOING TO BE
KIND OF A WAIT PERIOD.
AND THEN THE OTHER GROUP IS
IMMEDIATE TREATMENT.
WHAT I LOVE ABOUT THIS DESIGN IS
SIMILAR TO DISCUSSION YESTERDAY
WHERE THERE IS THAT VIRTUAL
TWIN, THE PATIENT IN THE WAIT
LIST GROUP CAN ALMOST SERVE AS
THEIR ACTUAL TWIN, SO AFTER THE
8-WEEK PSG, BOTH GROUPS GET AN
8-WEEK PSG AND LAB PSG AND THE
WAIT LIST GROUP THEN IS OFFERED
THE DEVICE SO EVERYBODY GETS TO
TRIAL THE DEVICE AND THEN
THERE'S A 16-WEEK PSG.
INCLUSION CRITERIA ARE FOR
CONDITIONS WITH PHARYNGEAL
HYPOTONIA, SO DOWN SYNDROME,
CEREBRAL PALSY, SEVERE OSA,
REALLY THE BIG EXCLUSION
CRITERIA I'LL HIGHLIGHT IS
DISTAL AIRWAY COLLAPSE, SO THE
DEVICE CAN'T BE INTUBATING THE
PATIENT SO IF THERE'S
OBSTRUCTION AT THE LEVEL OF THE
VOCAL CORDS OR MORE DISTAL, THAT
WOULD BE AN EXCLUSION CRITERIA.
A COUPLE SNAPSHOT PATIENTS FROM
THE R61 TRIAL, THIS IS A DOWNS
PATIENT WHO HAD UNDERGROUND
MULTIPLE DISE DIRECTED
SURGERIES, WAS NOT A CANDIDATE
FOR A -- WAS NOT TOLERATING CPAP
DESPITE NUMEROUS ATTEMPTS WITH
SLEEP PSYCHOLOGISTS, SO WE WOULD
KIND OF CATEGORIZE THEM AS A
POTENTIAL TRACH CANDIDATE WITH
PERSISTENT REALLY PROFOUND
OBSTRUCTIVE SLEEP APNEA WITH AN
AHI OF 69 WE THE DEVICE, THAT
AHI COMES DOWN TO 17.8.
IF WE UTILIZE A MEDICARE
CRITERIA, IT WOULD BE 8.1, AND
INTERESTINGLY, THE RECOMMEND REP
WHICH REALLY THERE WAS NOT MUCH
AT ALL AT BASE LIERNTION WE
START TO SEE EMERGENCE OF REM
SLEEP.
PATIENT TWO, JUST TO LOOK AT, IS
A PATIENT WITH SEVERE CEREBRAL
PALSY.
AND SEVERE UPPER AIRWAY
OBSTRUCTION EVEN AWAKE, CPAP WAS
NOT DEEMED TO BE A SAFE OPTION
BECAUSE OF THE ASPHYXIATION
ASPIRATION RISK, SO WE WOULD
AGAIN CONSIDER THIS PATIENT
POTENTIAL FOR TRACHEOSTOMY TO
ADDRESS THEIR OBSTRUCTIVE SLEEP
APNEA.
THEIR AHI IS 6.7, BUT
IMPRESSIVELY, THEIR HYPOXIA
IS -- THE MINIMUM O2 SAT IN THE
60s AND A GOOD PERCENTAGE OF
THE NIGHT HYPOXIC, WITH THE
DEVICE, THAT AHI COMES DOWN TO
LESS THAN 1, THE O2NATOR
IMPROVES TO STAYING IN THE
90s, AND AGAIN, WE SEE REALLY
NOT MUCH REM SLEEP BUT WE START
TO SEE SOME RESTORATION OF REM
SLEEP.
IMPORTANTLY, NO DEVICE-RELATED
ADVERSE EVENTS, SERIOUS DEVICE
ADVERSE EVENTS.
INTERESTINGLY, YOU KNOW, AS WE
THINK ABOUT A NON-SURGICAL AND
SURGICAL APPROACH, IN THE EVENT
OF A CONCERN FOR SOMETHING LIKE
A RECALL, A NON-SURGICAL
APPROACH LIKE THIS, LIKE CPAP,
IS FAIRLY EASY TO ADDRESS,
WHEREAS AS WE THINK ABOUT
SURGICAL INNOVATIONS, SOMETHING
OF THAT NATURE WOULD BE MUCH
MORE DIFFICULT TO ADDRESS.
SO KIND OF THINKING ABOUT
SURGICAL INNOVATION AND EMERGING
OPTIONS ON THE SURGICAL
STANDPOINT, HYPOGLOSSAL NERVE
STIMULATOR IS AN INTERESTING
APPROACH TO CONSIDER.
I THINK THAT AS WE THINK ABOUT
KIND OF THE INHERENT CHALLENGES
OF IMPLANTS, AGAIN IF A DEVASE
FAILS AND THERE IS A RECALL,
IT'S A MUCH MORE SERIOUS AND
CHALLENGING RISK.
AGAIN IF THE PATIENT HAS TO GO
BACK TO THE OPERATING ROOM, WE
KNOW THEY'RE PERIOPERATIVE HIGH
RISK PATIENTS.
THERE DOES SEEM TO BE SOME
IMPROVEMENT, AS DR. CIELO
HIGHLIGHT, IN THE -- ABOUT 36%
HAD TREATMENT TO LESS THAN AHI5,
BUT IT'S NOT ACROSS THE BOARD
CERTAINLY AND THINKING ABOUT
WHAT TREATMENT RESPONSE IS, I
THINK IS CRITICAL.
WHEN WE LOOK AT KIND OF LONG
TERM FOLLOW-UP AND LONG TERM
POTENTIAL COMPLICATIONS, HART
NICK'S GROUP, DR. HARTNICK OUT
OF BOSTON REALLY HAS LED THE WAY
AND HAS DESCRIBED SOME OF THE
POTENTIAL CHALLENGES WITH HAVING
TO REPLACE BATTERIES AND HAVE
OTHER ISSUES FROM THE SURGICAL
STANDPOINT.
THEN I THINK IT'S GOOD TO KIND
OF CONSIDER COST, SO HOW
ACCESSIBLE IS THIS TREATMENT
OPTION, BOTH IN THE STATES AND
LOW/MIDDLE RESOURCE
ENVIRONMENTS.
THE TAKE-HOME POINTS THAT I'LL
HIGHLIGHT IS CLEARLY IN THESE
VULNERABLE POPULATIONS, THERE'S
A DIRE NEED FOR ADDITIONAL
TREATMENT OPTIONS THAT CAN REACH
ALL POPULATIONS.
I THINK IT'S REALLY FASCINATING
TO THINK ABOUT AS NEW TREATMENT
OPTIONS EMERGE, HOW THAT MAY
DRIVE ADDED KNOWLEDGE TO
INFORMATION.
I'VE SPOKE WITH DR. COLIN
SULLIVAN, FASCINATING TO HEAR
HOW THE DEVELOPMENT OF CPAP
REALLY KIND OF PRECEDED FULL
UNDERSTANDING OF SLEEP MEDICINE,
SO PERHAPS WE'LL LEARN MORE AS
THESE TREATMENT OPTIONS EMERGE.
GOOD TO HIGHLIGHT THAT THE
STANDARD -- THE GOLD STANDARD
TREATMENT OPTIONS ARE OFTEN NOT
FEASIBLE FOR THESE VULNERABLE
PATIENT POPULATIONS, AND SO
REALLY KIND OF HAVING TO THINK
MULTIMODAL AND INNOVATIVELY TO
ADDRESS THEIR SLEEP CHALLENGES,
AND THEN FUNDING FOR HIGHER RISK
INNOVATIVE SOLUTIONS LIKE THIS
REALLY I THINK WILL DRIVE
EVIDENCE-BASED CLINICAL
SOLUTIONS.
THANK YOU AGAIN SO MUCH FOR THE
OPPORTUNITY TO DISCUSS THESE
EMERGING OPTIONS.
>> THANK YOU, DR. ZOPF.
MY CAMERA WON'T WORK -- OH,
THERE WE GO.
SO I'M JUST GOING TO SUMMARIZE
REALLY QUICKLY WHAT WE JUST
HEARD AND THEN WE'LL JUMP INTO A
Q & A UNTIL ABOUT 2:10 OR SO AND
THEN WEAL TAKE A MORE
ABBREVIATED BREAK.
DR. CIELO DISCUSSED THE UNIQUE
SCREENING AND MANAGEMENT OF OSA
IN DOWN SYNDROME POINTING OUT
SEVERAL GAPS IN OUR CURRENT
KNOWLEDGE AND IN NATURAL HISTORY
AND TERRITORIMENT OPTIONS
AND TREATMENT OPTIONS.
HE ADDRESSED SOME CURRENT
CLINICAL TRIALS TO ADDRESS OSA
AND DOWN SYNDROME THAT ARE BEING
SUPPORTED BY THE NIH.
DR. ZOPF HIGHLIGHTED THE
SHORTCOMINGS OF TRADITIONAL
PEDIATRIC TREATMENT PATHWAYS FOR
OSA WHEN APLAYED TO CHILDREN APN
WITH CERTAIN DEVELOPMENTAL
DISABILITIES INCLUDING CEREBRAL
PALSY, DOWN SYNDROME AND
HYPOTONIA IN GENERAL.
HE DISCUSSED THE IMPORTANCE OF
MULTIMODAL INDIVIDUALIZED
TREATMENT PLANS AND REA VEALED
SOME POTENTIAL INNOVATIVE
SOLUTIONS INCLUDING SELF
SUPPORTED AIRWAY DEVICES BUT
ALSO MENTIONED THE NEED FOR
ADDITIONAL OPTIONS.
SO WITH THAT, WE'LL KIND OF
OPENED IT UP TO QUESTIONS, AND I
SEE A FEW IN THE CHAT.
ONE, I THINK DR. CIELO STARTED
ANSWERING BUT I JUST WILL
VERBALLY TALK ABOUT IT.
THIS IS FROM DR. REDLINE.
ANECDOTALLY I'VE BEEN IMPRESSED
OVER THE HUGE DIFFERENCES IN OSA
SEVERITY IN DOWN SYNDROME IN
N3 VERSUS REM.
DO YOU THINK STAGE DIFFERENCES
IN DOWN SYNDROME ARE DIFFERENT
THAN IN OTHER PEDIATRIC
POPULATIONS, AND HOW DO WE LEARN
FROM STAGE-SPECIFIC CHANGES TO
DESIGN NEW TREATMENTS?
>> I THINK IT'S AN IMPORTANT
QUESTION, AND THERE'S A LOT OF
VARIABILITY, I THINK.
THERE HAVE BEEN PATIENTS WITH
DOWN SYNDROME WITH REALLY SEVERE
OBSTRUCTIVE SLEEP APNEA WHERE
STILL THERE IS VERY -- THERE ARE
VERY FEW EVENTS IN N3 SLEEP.
IT'S NOT TOTALLY UNCOMMON FOR
THAT TO HAPPEN IN CHILDREN SO
CERTAINLY SEEN IN OTHER WIRN
CHILDREN WITH PRETTY SEVERE
SLEEP APNEA.
I THINK THERE'S A LOT OF
VARIABILITY THERE, AS I THINK I
MADE MENTION IN THE COMMENT.
THIS IS AN OPPORTUNITY BECAUSE
WE HAVE A NUMBER OF THERAPEUTIC
TRIALS GOING ON, THE WORK THAT
DR. ZOPF IS DOING AND THEN SOME
OF THE STUFF I MENTIONED.
I THINK AS WE GENERATE THESE
LARGER COHORT OF PATIENTS WHO
ARE UNDERGOING ONE OR MAYBE
MULTIPLE THERAPIES, FOR EXAMPLE,
JUST CPAP TO BETTER UNDERSTAND
WHICH OF THESE PATIENTS ARE
GOING TO RESPOND BETTER TO
DIFFERENT THERAPIES.
BECAUSE AGAIN AS I MENTIONED
THIS IS A GROUP OF WHERE THERE
ARE A LOT OF HOWEVER YOU WANT TO
DEFINE NON-RESPONDERS, THERE ARE
A LOT OF NON-RESPONDERS.
AND IT MAY BE THAT ONE THERAPY
MAY BE BETTER FOR ONE PATIENT
AND MAYBE THAT THEY NEED
MULTIPLE THERAPIES.
AND I THINK THIS IS ONE OF
PROBABLY MULTIPLE DIFFERENT
THINGS TO LOOK AT IN TERMS OF
WHICH THERAPIES ARE GOING TO BE
MOST HELPFUL.
JUST BUILDING ON SOME OF THE
OTHER TALKS THAT WERE MADE ABOUT
THINGS LIKE AROUSAL INDEX AND
SOME OF THE SYMPTOMS IN TERMS OF
WHETHER IF YOU WERE TO THINK
ABOUT DIFFERENT CLUSTERS,
BUILDING ON WHAT DR. PACK HAD
MENTIONED IN THE ADULT
COMMUNITY, SO CLUSTERS OF
PEDIATRIC PATIENTS WITH DOWN
SYNDROME OR OTHERWISE WHO
PRESENT WITH DAY TIME SYMPTOMS
IN TERMS OF SLEEPINESS, AGAIN,
WHICH OF THESE THERAPIES ARE
GOING TO ADDRESS THOSE DAY TIME
SYMPTOMS OR THOSE
NEURODEVELOPMENTAL SYMPTOMS.
I THINK WE'RE RIGHT NOW GETTING
INTO A POSITION WHERE WE CAN
ANSWER SOME OF THOSE QUESTIONS
AND IT'S REALLY EXCITING.
>> THANK YOU.
ALL RIGHT.
WE HAVE A QUESTION FROM THE
VIDEOCAST WEBSITE.
THIS IS FOR DR. ZOPF.
HOW ARE YOU ACCOUNTING FOR THE
HIGH DEGREE OF VARIABILITY WITH
REA INSPECRESPECT TO WHAT'S LABS
CEREBRAL PALSY IN YOUR STUDIES?
>> THAT'S A GREAT POINT.
I THINK THAT, YOU KNOW, THE
PATIENTS THAT ARE IN THE STUDY
TEND TO BE MORE FUNCTIONALLY
IMPACTED, GM, FCS, YOU KNOW,
4s AND 5s, MORE SEVERELY
IMPACTED WITH MORE SIGNIFICANT
PHARYNGEAL HAY POE TONYA,
TYPICALLY WHEELCHAIR BOUND, SO
GREAT CONSIDERATION AND THERE IS
THAT HIGH VARIABILITY.
I THINK AS WE GET MORE
EXPERIENCE WITH THIS MO VEL
APPROACH, WE'LL BEGIN TO KIND OF
EXPLORE ARE THERE SUBPOPULATIONS
OF CP WHICH ARE BETTER
RESPONDERS, ARE THERE PATIENTS
WITH ADDITIONAL COMORBIDITIES
THAT THE APPROACH IS MORE
EFFECTIVE OR LESS EFFECTIVE FOR.
AND WE KNOW THAT A NUMBER OF
THESE PATIENT -- THE CEREBRAL
PALSY PATIENTS IN PARTICULAR CAN
HAVE SEIZURE DISORDERS, OTHERS
CAN HAVE OTHER COMORBIDITIES AND
HOW ARE THOSE SUBPOPULATIONS
KIND OF MORE OR PERHAPS LESS
RESPONSIVE.
MY HOPE IS THAT THE APPROACH
THAT WE'VE TAKEN A ANATOMICALLY
WHERE IF YOU THINK ABOUT CPAP,
IT IS KIND OF LIKE A PNEUMATIC
STENT, AND THE DEVICE THAT WE
DEVELOPED IS KIND OF LIKE A SOFT
SILICONE PHYSICAL STENT BUT I
THINK VERY MUCH EMLATES WHAT
CPAP TRIES TO DO AND SO EARLY IN
THE DEVELOPMENT OF OUR CLINICAL
TRIAL, WE THOUGHT, BOY, WE COULD
REALLY NARROW THE POPULATION
THAT WE LOOK AT AND TRY TO KIND
OF TEE OURSELF UP FOR A SUCCESS.
OR WE CAN LOOK AT A MORE
HETEROGENOUS POPULATION AND SEE
DOES IT SEEM TO BE MORE
EFFECTIVE FOR OR LESS EFFECTIVE
FOR PATIENTS WITH OBESITY, WITH
SOME OTHER COMORBIDITIES, SO OUR
HOPE IS THAT IT'S MORE BROADLY
EFFECTED BECAUSE AFFECTED BECAUH
THAT IT TAKES.
>> THANK YOU, DR. ZOPF.
ALL RIGHT.
I HAVE ANOTHER QUESTION FOR
DR. CIELO.
REALLY EXCELLENT AND IMPACTFUL
WORK, CHRIS.
CAN YOU SHARE YOUR THOUGHTS
ABOUT WHAT INSTITUTIONAL AND
BROADER SYSTEM-RELATED FACTORS
WOULD BE NEEDED TO SUCCESSFULLY
SCALE HSAT FOR CHILDREN WITH
DOWN SYNDROME VERSUS CHILDREN
THAT ARE TYPICALLY DEVELOPING
AND/OR ARE NOT MEDICALLY
COMPLEX.
WOULD IT BE MORE EFFECTIVE TO
SCALE GIVEN SOME OF THE
CHALLENGES WITH H SAT
SENSITIVITY SPECIFICITY AND
SENSORY DIFFERENCES ACROSS
POPULATIONS?
>> I THINK THAT IN MY IDEAL
DREAM WORLD, YOU WOULD HAVE
CLINICIANS WHO HAVE EXPERTISE IN
SLEEP MEDICINE THAT UNDERSTAND
THE LIMITATIONS AND THE BENEFITS
OF THESE DIFFERENT INSTRUMENTS,
WHETHER IT'S SOMETHING THAT'S
VERY SIMPLISTIC USING SOMETHING
LIKE A PULSE OXIMETER ALL THE
WAY THROUGH FULL POLYSONOGRAPHY
AND ALSO KNOWS THE RESOURCES
THAT ARE AVAILABLE LOCAL LEGAL
TO THEM AND THAT ALSO IS SEEING
THE PATIENT IN THE CLINIC AND
CAN SAY I KNOW WHAT THE
RESOURCES ARE OF THIS FAMILY AND
WIWHAT THE POSSIBILITIES ARE AND
HAVE THAT DISCUSSION TO THE
FAMILY AND TO BE ABLE TO SAY
OKAY, BASED ON YOUR NEEDS, MY
INDEX OF SUSPICION FOR SLEEP
APNEA AND KNOWING ALL THESE
DIFFERENT INSTRUMENTS, THIS IS
THE MODALITY I'M GOING TO
RECOMMEND TO DO THIS ASSESSMENT
FOR SLEEP APNEA.
I THINK THAT'S A PRETTY HIGH BAR
TO REACH, BUT RIGHT NOW WE'RE
NOWHERE NEAR THAT BECAUSE WE
REALLY ARE VERY LIMITED TO WHAT
INSTRUMENTS WE'RE GOING TO USE
TO TEST FOR SLEEP APNEA SO WE'RE
LEFT WITH THIS DISPARITY WHERE
IF YOU'RE IN AN AREA WITH LOTS
OF RESOURCES, IN A REALLY
EXCELLENT SLEEP LAB, YOU CAN
STUDY MOST PATIENTS WITH DOWN
SYNDROME OR OTHER SIMILAR
CONDITIONS LIKE A LOT OF THE
PATIENTS DR. ZOPF IS TALKING
ABOUT, ALSO VERY CHALLENGING
TOO, YOU CAN GET A GOOD RESULT
AND THEN YOU HAVE THE RESOURCE
THERE TO TREAT THEM WITH ALL
THESE AVAILABLE POTENTIAL
OPTIONS, SURGICAL, NON-SURGICAL,
CPAP, ET CETERA.
BUT NOT EVERYONE HAS THOSE
OPTIONS AVAILABLE TO THEM.
AND SO I THINK THINKING MORE
BROADLY LIKE WE NEED TO INVEST
IN ALL THE STUFF THAT'S BEEN
DISCUSSED.
YESTERDAY AND TO SOME EXTENT
TODAY, DEALING WITH SOME OF THE
ARTIFICIAL INTELLIGENCE MODELS,
BIG DATA ANALYSIS, AND THEN
LOOKING -- PARTNERING WITH
ENGINEERS, DATA SCIENTIST AND
OTHERS TO TRY TO UNDERSTAND
THESE DIFFERENT MODALITIES AND
KNOW HOW THEY WORK IN DIFFERENT
POPULATIONS LIKE THOSE WITH DOWN
SYNDROME.
I THINK WE HAVE AN OPPORTUNITY
IN DOWN SYNDROME BECAUSE THERE'S
REAL FUNDING AVAILABLE TO DO
SOME OF THESE STUDIES AND THESE
BIG COHORTS THAT ARE AVAILABLE.
I THINK SOME OF THE POPULATIONS
THAT DR. ZOPF IS DEALING WITH,
IT EVEN MORE CHALLENGING BECAUSE
SOME OF THESE ARE EVEN MORE RARE
DISEASES, THERE'S MORE
HETEROGENEITY AND MAY BE HARDER
TO DO THOSE KIND OF STUDIES.
SO I THINK THAT'S SORT OF WHERE
I WOULD LOVE PEDIATRIC FIELD TO
GO, AND I'M JUST DISCLOSURE, I'M
PART OF THE AMERICAN ACADEMY OF
SLEEP MEDICINE TASK FORCE THAT'S
LOOKING AT THE EVIDENCE IN HOME
SLEEP TESTING IN CHILDREN AND
IT'S REALLY TOUGH BECAUSE IT'S
ALL OVER THE PLACE AND A LOT OF
THESE STUDIES WERE VERY SMALL
STUDIES, THEY WERE DONE
CLINICALLY OUTSIDE THE UNITED
STATES LIKE DURING COVID OR
OTHER SITUATIONS, SO PUTTING
TOGETHER THOSE DATA, IT'S VERY
CHALLENGING.
BUT I THINK MORE WORK NEEDS TO
BE DONE IN THIS AREA.
>> THANK YOU.
GREAT INNOVATION.
HOW IS THE COMPLIANCE OR
DESENSITIZATION PROCESS?
DO YOU THINK A SIMILAR STRATEGY
FOR THE ORAL AIRWAY MIGHT BE
HELPFUL?
>> GREAT QUESTION.
I THINK HAVING THE INDEX
POPULATION HAVING BE CEREBRAL
PALSY AND DOWN'S AS WELL, THE
MORE HIGHLY IMPACTED PATIENT
LAKE THE PATIENT IN THE VIDEO, I
WILL SAY THERE IS ALMOST KIND OF
RELIEF AND YOU COULD SEE THAT
YOUNG BOY SMILE WHEN HE GOT THE
DEVICE, SO AS YOU WOULD IMAGINE,
BEING ABLE TO BREATHE IS A
BENEFICIAL THING, SO THERE TENDS
TO BE, IN THAT POPULATION,
REALLY WARM RECEPTION TO THE
DEVICE.
IN THE DOWN'S POPULATION, I
THINK IT'S HIGHLY DEPENDENT ON
THE CAREGIVER, AND SO I THINK
WITH KIND OF ACCLAMATION TO USE
OF THE DEVICE, WHAT WE FOUND WAS
TO BE MOST HELPFUL IS CERTAINLY
IF CAREGIVERS ARE INVESTED AND
IF THEY CAN INCORPORATE
PLACEMENT OF THE DEVICE AND A
BEDTIME ROUTINE, IT SEEMS LIKE
THAT ROUTINE FOR THE DOWN'S
POPULATION SEEMS TO BE REALLY
VALUABLE.
AND SO COMPLIANCE IS HIGH IF THE
FAMILY IS ABLE TO KIND OF
INTEGRATE IT IN A BEDTIME
ROUTINE.
INTERESTINGLY, ANOTHER APPROACH
THAT'S BEEN SUCCESSFUL IS
PLACING IT AFTER THE CHILD'S
GONE TO SLEEP, AND IT'S BEEN
SUPER VALUABLE FOR ME HEARING
ABOUT SOME OF THE THRESHOLD DATA
TOO, AND IT MAKES ME WONDER IF A
TREATMENT APPROACH LIKE THIS,
YOU KNOW, COULD BENEFIT FROM
ADJUNCTIVE THERAPIES LIKE BEING
ABLE TO MODIFY SOME OF THOSE
AROUSAL THRESHOLDS, AND SO --
>> GREAT, THANK YOU.
I THINK THIS QUESTION COULD BE
FOR BOTH OF YOU FROM DR. TASALI.
WHAT ARE YOUR THOUGHTS ON
NOTICEABLE VERSUS VALUABLE
CHANGE, AS I TRIED TO ALLUDE TO
IN MY TALK, FOR DOWN SYNDROME
PATIENTS AND CAREGIVERS?
>> IT'S SUCH A FASCINATING
QUESTION.
I THINK IT'S SOMETHING THAT I'VE
SEEN A LOT IN MY DISE DIRECTED
SURGERIES OR REALLY ANY
INTERVENTION WHERE SOMETIMES
FAMILIES WILL COME BACK REALLY
HAPPY AND CAREGIVERS WILL SAY
BOY, THINGS SEEM A LOT BETTER,
AND THEN WE MIGHT GET A POST-OP
PSG WHICH SHOWS THERE MAY BE
IMPROVEMENT BUT THERE'S STILL
SLEEP APNEA.
I THINK IT KIND OF HARPS ON THE
QUESTION WHAT IS KIND OF
TREATMENT SUCCESS AND KIND OF
WHAT'S THE END POINT IN THESE
VULNERABLE POPULATIONS?
IS IT THE SAME AS CHILDREN
WITHOUT THESE VULNERABLE
POPULATIONS?
AND THAT TENDS TO BE KIND OF
WHERE THERE'S DISCORDANCE, IN MY
EXPERIENCE, WHERE I'M KIND OF
STRUGGLING WITH THERE SEEMS TO
BE IMPROVEMENT IN QUALITY OF
LIFE, THERE SEEMS TO BE IMPROVED
KIND OF CAREGIVER AND PATIENT
CLINICAL RESPONSE, BUT THAT MAY
NOT ALWAYS PAIR UP CLOSELY WITH
THE PSG FINDINGS.
>> I'LL JUST ADD THAT I THINK
THE DISCUSSION OF RESPONSE
VERSUS NON-RESPONSE IS SOMETHING
THAT'S REALLY, REALLY IMPORTANT
AND JUST I THINK IN PEDIATRICS,
THERE'S JUST A LOT OF OUTCOMES
THAT ARE SIMILAR TO TRIALS IN
ADULTS BUT THERE'S OTHERS THAT
ARE DIFFERENT.
SO I MEAN, YOU ALWAYS HAVE A
PARENT THAT'S PART OF THE
EQUATION AS WELL AND ESPECIALLY
LIKE YOUNGER KIDS THAT HAVE
OBSTRUCTIVE SLEEP APNEA, THE
PARENT IS OFTEN IMPACTED TOO.
THEIR SLEEP CAN BE IMPACTED,
THEIR ABILITY TO DA CARE FOR THR
CHILD CAN BE IMPACTED.
SOMETIMES IT'S NOT THE CONDITION
ITSELF, JUST PAU BECAUSE OF THER
WORRY ABOUT IT.
PARENTS ARE UP ALL NIGHT BECAUSE
THEY'RE WORRIED THAT THEIR CHILD
CAN'T BREATHE, AND IN SOME
CASES, THEY HAVE GOOD REASON FOR
THAT CONCERN.
AND SO PARENT REPORTED QUALITY
OF LIFE AND PARENT REPORTED
OUTCOMES, I THINK ARE AN
IMPORTANT MEASURE THAT WE NEED
TO CONSIDER TOO, BECAUSE IT CAN
REALLY AFFECT THE WHOLE FAMILY
IN SOME OF THESE CASES.
BUT IN OTHER CASES, FOR EXAMPLE,
A CHILD WITH DOWN SYNDROME THAT
HAS POOR SLEEP, EITHER THEY'RE
NOT SLEEPING WELL OR HAVE SLEEP
APNEA OR BOTH, IT AFFECTS THEIR
DAY TIME ACTIVITY TOO AND THAT
CAN IMPACT THE REST OF THE
FAMILY AND THERE CAN JUST BE A
LOT OF DOWNSTREAM CONSEQUENCES.
SO WE SHOULD THINK MORE BROADLY
ABOUT RESPONDERS IN TERMS OF
THESE THERAPIES.
SOMETIMES WITH THE AHI, HOW THAT
GOES DOWN OR CHANGES, BUT I
THINK ALSO HOW IT'S AFFECTING
DIET NA MIX AND THE FAMILY OF
THE CHILD'S WELL-BEING AND JUST
TO BE MORE BROAD ABOUT THAT.
AGAIN I'LL JUST KEEP MENTIONING
THAT SOME OF THESE COHORT
STUDIES, I THINK WITH A LOT OF
THOSE DEMOGRAPHIC KIND OF
FACTORS WILL BE A GREAT RESOURCE
TO TRY TO LOOK AS WE THINK ABOUT
CLINICAL TRIALS IN THESE
POPULATIONS.
>> OKAY, I THINK WE HAVE TIME
FOR ONE LAST QUICK QUESTION.
DR. ZOPF, GREAT TALK.
DO YOU ANTICIPATE THE DEVASE
WORKING DIFFERENTLY OR HAVING
MORE RISK FOR ADVERSE EFFECT
SUCH AS BLEADING B BLEEDING BASN
REASONS BEHIND NASAL OBSTRUCTION
FOR INSTANCE, TISSUE
HYPERTROPHY --
>> GREAT QUESTION.
WITH DR. CIELO'S COMMENT, ONE OF
THE QUALITY OF LIFE INDICES THAT
WE'RE LOOKING AT IN THE STUDY IS
FAMILY IMPACT, AND I WILL SAY
PARTICULARLY THE CP POPULATION,
IT'S ASTOUNDING HEARING
ANECDOTAL RESPONSES FROM PARENTS
WHERE THEY WERE GETTING UP KIND
OF MULTIPLE TIMES PER HOUR TO
MAKE SURE THEIR CHILD WAS STILL
BREADTHING AND THEN KIND OF
HAVING THAT MORE PEACE OF MIND
BEING ABLE TO SLEEP THROUGH THE
NIGHT FROM THE CAREGIVER SIDE.
AS FAR AS CONCERNS FOR BLEEDING
OR TISSUE OBSTRUCTION, IN
PLACING THE DEVICE, WE KIND OF
UTILIZE APPROACH ALMOST SIMILAR
TO ENDOTRACHEAL TUBE SIZING, SO
IT'S NOT CUSTOM FOR EACH
PATIENT, BUT THERE ARE KIND OF
LIKE HALF COUNCILME CENTIMETER .
INITIALLY WE'LL DO AN ENDO
SCOPIC EXAM DURING CLINIC AND
MAKE SURE THERE'S NOT SOMETHING
LIKE A POLYP OR JUVENILE ANG JOE
FIBROMA OR OTHER MASS THAT COULD
BE CONCERNING.
IT COULD ALSO GIVE US SOME HINTS
AS TO WHICH SIDE MIGHT BE BETTER
TO PLACE THE DEVICE ON.
PRETTY ASTOUNDINGLY, AND I'LL
KNOCK ON WOOD, WE'VE NOT HAD
ISSUES WITH EP EP EPISTAXIS, SE
DEVICE IS COMPOSED OF MEDICAL
GRADE SILICONE, IT'S QUITE SOFT,
AND SO HAVING HYPERVASCULAR
MUCOSA OR AGAIN WE DO KIND OF
SCREEN FOR ANY CONCERNING
ANATOMIC OBSTRUCTION, BUT
FORTUNATELY IT'S NOT BEEN AN
ISSUE.
>> GREAT.
ALL RIGHT.
THANK YOU SO MUCH, DR. ZOPF AND
DR. CIELO.
WITH THAT, I THINK WE'LL
CONCLUDE THIS SESSION AND
EVERYONE WILL HAVE A BREAK.
I THINK ALFONSO AND EVERYONE,
THE PLAN IS FOR PEOPLE TO COME
BACK AT 2:15, IS THAT RIGHT,
FIVE MINUTES?
>> FIVE MINUTES IS WHAT WE'VE
GOT.
>> ALL RIGHT.
SO WE'LL RECONVENE THEN.
THANKS, EVERYBODY.
>> OKAY.
SO JUST VERY QUICKLY, MY
DISCLOSURES, NOTHING RELEVANT TO
THIS CONVERSATION.
I WANT TO DO THE FOLLOWING.
I WANT TO TALK ABOUT THE
DISTINCTION BETWEEN
IMPLEMENTATION, IMPLEMENTATION
RESEARCH, AND IMPLEMENTATION
SCIENCE.
THEY ARE ALL CONNECTED BUT THERE
ARE SOME KEY DIFFERENCES THAT I
THINK ARE IMPORTANT FOR THE
FUTURE OF OSA RESEARCH.
MOST OF WHAT I WILL DO IS PREND
PRESENT A BRIEF OVERVIEW OF
IMPLEMENTATION SCIENCE THEORIES
AND FRAME WORKS BUT DOING THIS
STANDING ON ONE FOOT.
I REALLY APOLOGIZE IN ADVANCE IF
MY TALK COMES ACROSS AT EITHER
TOO BASIC AND SUPERFICIAL OR I
RACE THROUGH THEE THINGS.
THEN FINALLY, I WILL MENTION
VERY, VERY BRIEFLY A COUPLE OF
EXAMPLES FROM THE RECENT
LITERATURE OF IMPLEMENTATION
OUTCOMES IN STUDIES OF SLEEP
APNEA AND THEN CLOSE WITH A FEW
RECOMMENDATIONS.
SO JUST BY WAY OF BACKGROUND AS
DR. TASALI MENTIONED, I RUN
CLINICAL DIRECTORS NETWORK, A
PRIMARY CARE PRACTICE BASED
RESEARCH AND A NETWORK OF
PRACTICE BASED RESEARCH NETWORKS
THAT FOCUS IN PRIMARY CARE AND
MEDICALLY UNDERSERVED SETTINGS
ACROSS THE COUNTRY AND WE ALSO
WORK WITH SEVERAL OF THE PCORNET
CLINICAL DATA RESEARCH NETWORKS
AND THIS WILL BE IMPORTANT WHEN
I WRAP UP AND TALK ABOUT
RECOMMENDATIONS FOR FUTURE
STUDIES, THE NATURE OF WHICH MAY
BE MORE PRAG PRAGMATIC STUDIES O
I'LL COME BACK TO WHY THIS IS
IMPORTANT.
SO JUST TO BEGIN WITH SOME
DEFINITIONS, IF WE THINK OF THIS
AS A CONTINUUM WHERE QUALITY
IMPROVEMENT IS OFTEN FOCUSED ON
THE HERE AND NOW IN A LOCAL
SETTING, IMPLEMENTATION RESEARCH
IS MORE FOCUSED ON LOOKING AT
IMPLEMENTATION STRATEGIES ACROSS
MULTIPLE SETTINGS AND TRYING TO
UNDERSTAND HOW THEORY, COULD BE
TEXT, MEDIATORS, MECHANISMS
ADDRESS A GAP IN IMPLEMENTATION.
AND IMPLEMENTATION SCIENCE IS
THE STUDY OF METHODS TO PROMOTE
THE SYSTEMATIC UPTAKE OF
RESEARCH FINDINGS AND OTHER
EVIDENCE-BASED PRACTICES INTO
ROUTINE CARE, WHICH IF IT WORKS,
WILL IMPROVE THE QUALITY,
EFFECTIVENESS AND ACCESS TO
HEALTH SERVICES.
AND SO THE KEY DISTINCTION IN
THIS CONTINUUM IS THAT BOTH
IMPLEMENTATION RESEARCH AND
IMPLEMENTATION SCIENCE ARE
AIMING AND DEVELOPING
GENERALIZABLE KNOWLEDGE, AND
THAT I THINK IS AN IMPORTANT
DISTINCTION.
NIH ALSO BRINGS INTO THE PICTURE
DISSEMINATION RESEARCH, WHICH IS
TO UNDERSTAND THE PROCESSES AND
FACTORS THAT LEAD TO WIDESPREAD
AWARENESS AND UNDERSTANDING OF
EVIDENCE-BASED INTERVENTIONS,
BUT THAT THAT IS ON A CONTINUUM
AND IMPLEMENTATION RESEARCH
TRIES TO UNDERSTAND HOW THOSE
FINDINGS GET TAKEN UP,
IMPLEMENTED AND UNDERSTAND THE
PROCESSES THAT EITHER ACCELERATE
OR INHIBIT THEIR UPTAKE AND IN
PARTICULAR ONE OF THE AREAS
THAT'S VERY CRITICAL IN
IMPLEMENTATION RESEARCH HAS TO
DO WITH ADAPTATION AND HOW THE
SETTING INFLUENCES THE WAY IN
WHICH AN INTERVENTION OR
INNOVATION IS ACTUALLY
IMPLEMENTED.
SO THIS IS I THINK A GOOD
SYNOPSIS OF THE DISTINCTION
BETWEEN DISSEMINATION
IMPLEMENTATION, IMPLEMENTATION
INTERVENTION, IMPLEMENTATION
STRATEGY AND IMPLEMENTATION
RESEARCH, AND ALL MY SLIDES ARE
AVAILABLE SO THESE HAVE THE
REFERENCES AS WELL.
SO TAKING A STEP BACK, MOST OF
IMPLEMENTATION RESEARCH CAN
REALLY TRACE ITS ANCESTRY TO
RODGERS' THEORY OF THE DIFFUSION
OF INNOVATIONS WHICH FOCUSES ON
THE CHARACTERISTICS OF THE
INNOVATION, ORGANIZATION,
ENVIRONMENT THAT LEAD TO A
DECISION TO ADOPT OR NOT TO
ADOPT, WHICH LEADS TO EFFECTIVE
IMPLEMENTATION AND OUTCOMES.
THIS OF COURSE IS VASTLY
SIMPLIFIED AND MODERN
IMPLEMENTATION SCIENCE SEEKS TO
UNDERSTAND EACH OF THE ARROWS
BETWEEN THESE DIFFERENT KEY
ELEMENTS OF THE DIFFUSION AND
INNOVATION PROCESS.
SO ONE MODEL OR FRAMEWORK I HOPE
MANY OF YOU ARE FAMILIAR WITH
AND IF NOT, I WOULD POINT YOU TO
THE WORK ON RE-AIM, WHICH STANDS
FOR REACH, EFFECTIVENESS,
ADOPTION, IMPLEMENTATION, AND
MAINTENANCE.
AND THESE ARE A SERIES OF
VARIABLES THAT CAN BE MEASURED
IN A CLINICAL TRIAL OR
OBSERVATIONAL STUDY THAT HELP TO
UNDERSTAND THE DIFFERENT ASPECTS
OF IMPLEMENTATION.
WHAT'S THE FRACTION OF ELIGIBLE
PATIENTS THAT ARE REACHED, HOW
EFFECTIVE IS AN INTERVENTION,
HOW DO I ENHANCE THE LIKELIHOOD
THAT AN ORGANIZATION WILL MAKE A
DECISION TO ADOPT AN INNOVATION,
HOW DO I ENSURE THAT THIS IS
DELIVERED PROPERLY WITH HIGH
FIDELITY AND HOW CAN I DETERMINE
THAT IT'S SUSTAINED OVER TIME.
SO THESE ARE SOME OF THE KEY
ELEMENTS OF IMPLEMENTATION
SCIENCE, AND THERE ARE SOME
SUBSEQUENT MODIFICATIONS OR
INNOVATIONS TO RE-AIM, ONE IN
PARTICULAR CALLED QUEST, WHICH
KEEPS THE SAME SET OF VARIABLES
BUT ADDS A SERIES OF QUALITATIVE
AND ETHNOGRAPHIC AND
OBSERVATIONAL NON-INTERVENTIONAL
ASSESSMENTS TO REALLY TRY TO
UNDERSTAND THE PROCESS OF
ADOPTION, IMPLEMENTATION,
SUSTAINABILITY.
AND MORE RECENTLY, ANOTHER
INNOVATION IN RE-AIM IS REFERRED
TO AS PRISSMM, THE PRACTICAL
ROBUST IMPLEMENTATION AND
SUSTAINABILITY MODEL, WHICH IN
ADDITION TO THE SAME RE-AIM
CHARACTERISTICS, ALSO
CHARACTERIZES THE ORGANIZATIONAL
PATIENT PERSPECTIVES,
CHARACTERISTICS OF THE
ORGANIZATION, CHARACTERISTICS OF
PATIENTS, AND TRIES TO MODEL ALL
OF THESE ELEMENTS, AS WELL AS
THE INTECIAL INTERNAL AND EXTERL
ENVIRONMENT TO EXAMINE THEIR
IMPACT.
SO AGAIN THESE ARE THE ARROWS
BETWEEN THE ARROWS THAT LEND
THEMSELF TO CONCEPTUALIZATION
AND MEASUREMENT.
ANOTHER FRAMEWORK THAT YOU MAY
COME ACROSS OR HAVE SEEN IS
REFERRED TO AS THE CONSOLIDATED
FRAMEWORK FOR IMPLEMENTATION
RESEARCH, OR CFIR.
AND IT CHARACTERIZES
IMPLEMENTATION IN TERMS OF THE
OUTER SETTING.
THESE ARE NEIGHBORHOOD AND
COMMUNITY CHARACTERISTICS, THE
INNER SETTING ASPECTS OF THE
PRACTICE, ACCESS TO SPECIALISTS,
THE WORKFORCE, THE WORKFLOW, ET
CETERA, CHARACTERISTICS OF THE
PATIENTS.
IT LOOKS AT MEASURES OF PROCESS,
AND THEN IT LOOKS AT THE
ADAPTATION STARTING WITH THE
INTERVENTION IN ITS PUREST FORM,
AND THEN TRIES TO UNDERSTAND HOW
ALL OF THESE FACTORS AFFECT THE
ADAPTATION SO THAT THE
INTERVENTION CAN FIT WITHIN THE
SETTING WITHIN THE RESOURCES.
AND SO CFIR I THINK IS A VERY
IMPORTANT OTHER WAY TO LOOK AT
IT, AND AS I MENTIONED BEFORE,
PRISM, YOU'LL SEE HAS SOME OF
THE SAME MEASURES OF INNER AND
OUTER ORGANIZATIONAL
CHARACTERISTICS.
WHEN WE STUDY IMPLEMENTATION,
THERE ARE SOME KEY MEASURES WE
OFTEN LOOK AT AND A FEW EXAMPLES
OF THEM ARE FEASIBILITY,
FIDELITY, HOW WELL THE
INTERVENTION IS RE REPLICATED FM
PATIENT TO PATIENT, FROM
CLINICIAN TO CLINICIAN AND
SETTING TO SETTING.
PENETRATION, ACCEPTABILITY,
SUSTAINABILITY, UPTAKE, COSTS.
THESE ARE SOME OF THE
IMPLEMENTATION SCIENCE OUTCOMES
THAT ONE CAN BUILD INTO A STUDY,
AND OFTENTIMES AN IMPLEMENTATION
SCIENCE STUDY WILL LOOK AT
MULTIPLE IMPLEMENTATION
OUTCOMES.
THIS TRIES TO SCOPE OUT A LITTLE
BIT FURTHER WAYS IN WHICH WE CAN
LOOK AT ACCEPTABILITY, ADOPTION,
APPROPRIATENESS, FEASIBILITY, ET
CETERA, AND I WANT TO MENTION
THAT FIDELITY IS A PARTICULARLY
CHALLENGING QUESTION BECAUSE
PRIOR TO THE WIDESPREAD
DIFFUSION OF IMPLEMENTATION
SCIENCE, WE WOULD CONSIDER A
STUDY THAT HAD HIGH LEVELS OF
ADAPTATION, LOW FIDELITY, AND
HAD POOR INTERNAL VALIDITY.
I THINK IMPLEMENTATION SCIENCE
HAS HELPED US TO UNDERSTAND THAT
ANY IMPLEMENTATION STRATEGY
REQUIRES SOME ADAPTATION.
SO IN THINKING ABOUT THIS, THE
FIDELITY OR THE REPRODUCIBILITY
OF THE INTERVENTION REALLY WHEN
YOU THINK ABOUT ITS ADAPTATION
HAS A LOT MORE TO DO WITH ITS
GENERALIZABILITY.
SO HOW WELL CAN THIS
INTERVENTION STRATEGY WORK IN
DIFFERENT SETTINGS?
I THINK ABOUT OUR FEDERALLY
QUALIFIED HEALTH CENTERS WHERE I
KNOW OF ONLY ONE PULMONOLOGIST,
PERHAPS THERE ARE OTHERS BUT I
ONLY KNOW OF ONE, VERY FEW
PLACES THAT HAVE SLEEP LABS
WITHIN THEIR HEALTH CENTERS,
MANY HAVE ACCESS TO THEM THROUGH
COMMUNITY REFERRALS, SO ONE HAS
TO THINK ABOUT HOW DO YOU ADAPT
THE BEST PRACTICES IN THE
EVIDENCE-BASED STRATEGY SO THEY
CAN WORK IN LOW RESOURCE
SETTINGS.
SO ONE WAY TO APPROACH THIS THAT
I THINK HAS INCREASING
IMPORTANCE AT NHLBI AND
ELSEWHERE IS THE IDEA OF THESE
EFFECTIVENESS IMPLEMENTATION
HYBRID DESIGNS THAT ALLOW US TO
DESIGN THESE SO-CALLED HYBRID
STUDIES THAT LOOK AT BOTH
CLINICAL EFFECTIVENESS AND THE
EFFECTIVENESS OF DIFFERENT
IMPLEMENTATION STRATEGIES, AND
THEIR COMBINED EFFECT ON
IMPROVED OUTCOMES.
AND SO THIS IS AN AREA WHERE I
THINK THERE'S GREAT WORK TO BE
DONE IN OSA.
AND THERE ARE THREE TYPES OF
HYBRID STUDIES, THERE ARE MANY
SUBTYPES, WE HAVE ENDOTYPES
WITHIN THIS KIND OF STUDY
DESIGN, BUT IN A HYBRID TYPE 1,
THE FOCUS IS ON THE
EFFECTIVENESS QUESTION, AND WE
OFTEN THEN COLLECT PRELIMINARY
INFORMATION ON ITS
IMPLEMENTATION, A HYBRID TYPE
3 DOES THE REVERSE.
IT TAKES AS A GIVEN WE KNOW THAT
THE INTERVENTION IS CLINICALLY
EFFECTIVE, BUT WE WANT TO FOCUS
ON GATHERING THE MOST RIGOROUS
OUTCOMES ON ITS IMPLEMENTATION.
IT'S THE HYBRID TYPE 2 THAT
BALANCE OF 50/50 WHERE WE WOULD
DESIGN A STUDY THAT WOULD BE
POWERED TO DETECT THE MINIMALLY
DETECTABLE CLINICALLY AND
ORGANIZATIONALLY SIGNIFICANT
DIFFERENCES FOR AN INTERVENTION
AND ITS SETTINGS.
SO THE HYBRID TYPE 2 IS PERHAPS
THE MOST CHALLENGING BECAUSE IT
REQUIRES SAMPLE SIZES TO BE
ADEQUATE AT BOTH THE
EFFECTIVENESS OUT COME AND THE
IMPLEMENTATION OUTCOME.
WHEN WE THINK ABOUT THIS WHOLE
PROCESS, WE THINK ABOUT WAYS OF
DESIGNING INTERVENTIONS THAT CAN
BE DELIVERED IN DIFFERENT
SETTINGS.
THIS IS REFERRING TO EMERGING
CONCEPT OF DESIGNING FOR
DISSEMINATION AND
IMPLEMENTATION.
AND I THINK THIS IS AN AREA
WHERE THERE'S IMPORTANT WORK TO
BE DONE THAT ASKS THE QUESTION
HOW DO WE RETROFIT COMPLEX
MULTISTEP MULTILEVEL
IMPLEMENTATION STRATEGIES IN
BUSY COMPLICATED MEDICAL
PRACTICES THAT HAVE DIFFERENT
ACCESS TO DIFFERENT RESOURCES,
AND SO THE DESIGN PROCESS TAKES
MANY OF THESE INTO
CONSIDERATION.
WE ONLY HAVE TO THINK ABOUT
COVID VACCINATION AS BEING
HIGHLY EFFECTIVE BUT NOT,
PERHAPS, EASY TO DISSEMINATE AND
IMPLEMENT IN LOW RESOURCE
SETTINGS BECAUSE OF THE
REFRIGERATION REQUIREMENTS AND
OTHER HANDLING REQUIREMENTS.
SO DESIGNED FOR DISSEMINATION,
TRIES TO PUT MANY OF THESE
CHARACTERISTICS AT THE VERY
BEGINNING.
AND I'LL JUST LINK THIS TO THE
BROADER AREA OF COMPARATIVE
EFFECTIVENESS RESEARCH, WHICH IS
LOOKING AT DIFFERENT OPTIONS AND
OSA RESEARCH AS I UNDERSTAND IT
HAS DONE MANY IMPORTANT STUDIES
THAT HAVE COMPARED THE
EFFECTIVENESS OF DIFFERENT
DIAGNOSTIC AND THERAPEUTIC
INTERVENTIONS FOR HETEROJEEP HES
SETS OF PATIENTS.
PATIENT-CENTERED OUTCOMES BUILDS
ON COMPARATIVE EFFECTIVENESS
RESEARCH BUT FOCUSES ON OUTCOMES
THAT MATTER TO PEOPLE.
SO SOME OF THE PATIENT-CENTERED
OUTCOMES THAT I'VE COME ACROSS
HAVE TO DO WITH SYMPTOMS, DAY
TIME SLEEPINESS ABILITY,
FUNCTIONAL STATUS, COGNITIVE
STATUS.
THOSE ARE OUTCOMES THAT MATTER
TO PATIENTS THAT MAY NOT BE
ACCESSIBLE IN THE SAME RIGOR
THAT LUNG FUNCTION AND BREATHING
CAN BE ASSESSED.
BUT THEY CAN BE PUT TOGETHER, SO
CER AND PCOR HAVE A LOGICAL
AFFINITY FOR ONE ANOTHER, AND AS
I REVIEWED SOME STUDIES IN THIS
AREA, I SEE THIS AS ALS ALSO AST
FOR FUTURE WORK.
THE IDEA OF DESIGN TRIALS TO
INFORM DECISIONS IN PRACTICE,
AND PRAGMATIC TROILS GO BACK TOO
THAT CONCEPT OF ADAPTATION AND
FLEXIBILITY IN TERMS OF PATIENT
ELIGIBILITY, THE RECRUITMENT,
THE SETTING, THE ORGANIZATIONS,
THE ADHERENCE TO THE
INTERVENTION, THE ADHERENCE TO
ITS DELIVERY, THE FOLLOW-UP, AND
THE DECISION OF PATIENT
OUTCOMES.
WITH PRAGMATIC STUDIES, WE CAN
CHARACTERIZE HOW EXPLANATORY
VERSUS HOW PRAGMATIC A TRIAL IS
USING THIS WHEEL WHERE 5 IS THE
MOST PRAGMATIC AND 1 IS THE MOST
EXPLANATORY.
SO A PURE EXPLANATORY TRIAL
WOULD LOOK LIKE THIS WITH A
RADIUS OF 1 AND A PURE PRAGMATIC
TRIAL WOULD LOOK LIKE THIS WITH
A RADIUS OF 5, BUT IN PRACTICE,
IN THIS RECENT SUMMARY OF SERIES
OF PRAGMATIC TRIALS FROM THE NIH
COLLABORATORY, YOU CAN SEE THAT
MOST PRAGMATIC TRIALS LOOK MORE
LIKE AN IRREGULAR POLYGON, BUT
AS YOU CAN SEE IN THIS
DEMONSTRATION, 4s AND 5s ARE
THE MODAL LEVEL OF PRAGMATISM IN
THESE TRIALS.
AND SO THE DEGREE TO WHICH WE
CAN ADHERE TO SOME OF THESE
RECOMMENDED STRATEGIES WILL MAKE
THESE MORE LIKELY TO BE ADOPTED
AND IMPLEMENTED.
ONE STUDY THAT I DID WORKED WITH
A GROUP OF OLDER ADULTS HERE IN
NEW YORK CITY TO IMPLEMENT THE
DASH DIET AND HOME BLOOD
PRESSURE MONITORING THROUGH CON
CONGREGATE MEALS AND WELLNESS
PROGRAMS AND USING RE-AIM WE
REPORTED THAT WE REACHED ABOUT
HALF THE ELIGIBILITY PATIENTS,
WE LOWERED THE SYSTOLIC BLOOD
PRESSURE BY 4-MILLILITER OF
MERCURY, WE INCREASED THE
MAINTENANCE OF BLOOD PRESSURE
REDUCTION AT 7-MILLIMETERS OVER
SIX MONTHS AND THAT'S THE KIND
OF DROP YOU GET WHEN YOU ADD ONE
TO TWO MEDICATIONS.
SO THIS WAS TO ILLUSTRATE THE
WAY IN WHICH WE WERE ABLE TO
IMPLEMENT RE-AIM.
WHAT I WANTED TO DO IS BUZZ
THROUGH A COUPLE STUDIES I'VE
SEEN IN THE OSA LITERATURE
THAT'S REALLY NEW TO ME BUT
REALLY HIGHLIGHT SEVERAL STUDIES
WHERE A DIAGNOSIS, THIS STUDY
EXAMINED -- AND I APOLOGIZE IFI
GIVE SHORT SHRIFT TO MANY OF THE
AUTHORS WHO ARE PROBABLY IN THE
AUDIENCE, BUT LOOKING AT HOME
MONITORING VERSUS LABORATORY
MONITORING, CONCLUDING THAT IT
WAS FEASIBLE AND PREFERRED BY
PATIENTS.
SO IT GETS POSITIVE RANKING FOR
AN IMPLEMENTATION OUTCOME, IT'S
HYBRID EFFECTIVE IMPLEMENTATION
STUDY BECAUSE IT FINDS SIMILAR
EFFECTIVENESS IN DIAGNOSIS AND
AS A PATIENT-CENTERED OR PATIENT
PREFERRED OUT COME.
A SECOND STUDY LOOKED AT HOME
SLEEP APNEA CONCLUDED IT WAS
WELL TOLERATED AND PREFERRED IN
COMPARISON TO IN-LAB SLEEP
STUDIES BUT AT THE SAME TIME, I
NOTICED A THIRD STUDY THAT
SEEMED TO INDICATE THAT THE
IN-LAB STUDIES WERE MORE LIKELY
TO BE PREFERRED BY THE PATIENTS
IN THIS PARTICULAR TRIAL.
SO I THINK THE THINKING ABOUT
IMPLEMENTATION STRATEGIES IS THE
WAY IN WHICH ONE IMPLEMENTS BOTH
THE TESTING FOR OSA AND THEN
TURNING TO STUDIES OF TREATMENT,
THIS STUDY LOOKED AT HOME-BASED
INITIATION, CONCLUDING THAT IT
LED TO FASTER THERAPY ACCESS,
THIS STUDY FOUND THAT PATIENTS
WERE MORE LIKELY IN A COACHING
ARM TO A BRIEF TELEPHONE
COACHING ARM TO INCREASE THEIR
USAGE.
THIS STUDY SHOWED A DIGITAL
PLATFORM WAS VERY PROMISING IN
TERMS OF PATIENT ADHERENCE AND
THERAPY EXPERIENCE.
SO THESE GIVE ME GREAT HOPE THAT
THERE ARE A NUMBER OF DIFFERENT
IMPLEMENTATION STRATEGIES FOR
BOTH DIAGNOSIS AND THERAPEUTICS,
SO TO CONCLUDE IN THE TIME THAT
I HAVE ALLOCATED, I'D RECOMMEND
THAT THE DESIGN, CONDUCT AND
DISSEMINATION ACTIVITIES IN THE
FUTURE FOCUS ON PRAGMATIC
PATIENT-CENTERED HYBRID
EFFECTIVE AND IMPLEMENTATION
TRIALS THAT WE EXAMINE
IMPLEMENTATION STRATEGIES THAT
ENHANCED ACCESS TO CARE AND
HEALTH EQUITY AT THE PRACTICE,
PHYSIOLOGIC PATIENTS AND
POPULATION LEVELS, WE NEED TO
INCREASE THE DIVERSITY OF THE
PRACTICE SETTINGS IN WHICH THESE
STUDIES ARE CONDUCTED SO WE HAVE
BETTER EVIDENCE FOR
DISSEMINATION AND
IMPLEMENTATION, AND LIKEWISE THE
BROADER RANGE OF CLINICIANS AND
PATIENTS IN REAL WORLD SETTINGS
THAT COULD BENEFIT FROM BETTER
SCREENING TREATMENT DIAGNOSES
AND TREATMENT, AND FINALLY AS I
THINK I'VE HEARD SEVERAL TIMES,
IT'S GOING TO BE REALLY CRITICAL
TO DESIGN RECRUITMENT STRATEGIES
THAT WILL RECRUIT ADEQUATELY
POWERED SUBGROUPS SO THAT THE
HETEROGENEITY OF TREATMENT
EFFECTS CAN BE OBSERVED IN THE
BROADEST RANGE OF PATIENT
POPULATIONS, AND IN THE BROADEST
RANGE OF SETTINGS.
AND I WOULD URGE US TO BE
THINKING ABOUT PRINCIPLES OF
DESIGN FOR DISSEMINATION AT THE
POINT AT WHICH THESE STUDIES AND
INNOVATIONS ARE DEVELOPED
BECAUSE THESE ARE GOING TO BE
REALLY CRITICAL TO THEIR UPTAKE,
THEIR EFFECTIVENESS, AND THEIR
SUSTAINABILITY.
THANK YOU FOR THE OPPORTUNITY TO
SHARE SOME THOUGHTS AND
APPRECIATE ALL THAT I'VE LEARNED
IN THESE LAST TWO DAYS FROM
EVERYBODY.
>> THANK YOU, DR. TOBIN, FOR
THIS REALLY NICE OVERVIEW ON THE
KEY ELEMENTS OF IMPLEMENTATION
SCIENCE AND THEORIES.
WE DO NOT HAVE TIME FOR
QUESTIONS.
WE WILL MOVE ON TO THE NEXT TALK
BUT WE WILL TAKE QUESTIONS AT
THE END DURING THE Q & A
SESSION.
OUR NEXT SPEAKER IS DR. SARAH
HONAKER, WHO IS AN ASSISTANT
PROFESSOR OF PEDIATRICS AT
INDIANA UNIVERSITY SCHOOL OF
MEDICINE AND THE DIRECTOR OF
BEHAVIORAL SLEEP MEDICINE AT
RILEY CHILDREN'S HOSPITAL.
HER TALK IS TITLED
EVIDENCE-BASED PEDIATRIC OSA
DETECTION AND MANAGEMENT IN
PRIMARY CARE.
DR. HONAKER.
>> HAPPY TO BE HERE AND TALK TO
YOU TODAY EVIDENCE-BASED
PEDIATRIC OSA DETECTION AND
MANAGEMENT IN PRIMARY CARE
CLINICS.
SO MY GOAL TODAY IS TO TALK
ABOUT WHY PRIMARY CARE IS SUCH
AN IMPORTANT IMPLEMENTATION
SETTING IN PEDIATRICS, TO TALK
ABOUT THE CURRENT STATUS OF
EVIDENCE-BASED DETECTION AND
MANAGEMENT OF PEDIATRIC OSA IN
PRIMARY CARE, TO TALK ABOUT SOME
IMPLEMENTATION APPROACHES THAT
HAVE BEEN EMPLOYED AND HAVE
PROMISE AND THEN TO SUMMARIZE
GAPS AND OPPORTUNITIES.
THROUGHOUT I'M GOING TO TRY TO
HIGHLIGHT DIFFERENT SYSTEMS THAT
I THINK ARE CRITICAL, SO SOME OF
THE KEY PLAYERS, PROVIDERS,
FAMILIES, HEALTH SYSTEMS AND
COMMUNITIES.
SO PRIMARY CARE HAS UNIQUE
ACCESS TO FAMILIES.
SO THERE ARE 28 RECOMMENDED WELL
CHILD VISITS FROM BIRTH TO 18
YEARS.
AND THERE'S GOOD ADHERENCE WITH
THOSE AS WELL.
SO FOR IM EXAMP FOR EXAMPLE, INT
YOUTH HAD AT LEAST ONE WELL
CHILD CHECK.
IN ADDITION, THE AAP DOES
PEDIATRIC OSA GUIDELINES THAT
HAVE IMPLICATIONS FOR PRIMARY
CARE DELIVERY.
AND SPECIFICALLY, THESE ARE 2006
GUIDELINES.
SPECIFICALLY THEY NOTE THAT ALL
CHILDREN AND ADOLESCENTS SHOULD
BE SCREENED FOR SNORING.
IF A CHILD OR ADOLESCENT
SENATORS REGULARLY AND HAS ONE
OR MORE OF THE COMPLAINTS OR
FINDINGS SHOWN IN TABLE TWO,
THEN CLINICIANS SHOULD ORDER A
SLEEP STUDY OR COULD ALSO REFER
THE PATIENT TO SLEEP OR ENT FOR
FURTHER EVALUATION.
SO THAT'S THE IDEA.
BUT WHEN WE LOOK AT LITERATURE
EXAMINING PRACTICES IN PEDIATRIC
PRIMARY CARE, WE SEE RATES OF
SCREENING RAGE FROM 2 TO 25% IN
PEDIATRICS AND KEEP IN MIND THAT
NUMBER SHOULD BE 100%.
DIAGNOSIS IS AROUND 1%, AND WE
SUSPECT THAT SHOULD BE CLOSER TO
3 TO 5%.
AND WHEN CHILDREN WITH OSA AND
SLEEP DISORDER BREATHING ARE I'D
IDENTIFIED, RATES OF MANAGEMENT
ARE LOW.
IN ADDITION, WE SEE SIGNIFICANT
DISPARITIES BOTH IN THE
PREVALENCE AND SEVERITY OF
DISEASE, BUT ALSO IN THE RECEIPT
OF EVIDENCE-BASED CARE.
SO CHILDREN FROM MINORITIZED
RACIAL OR ETHNIC BACKGROUNDS
HAVE HIGHER RATES OF OSA, SO
THERE'S FOR EXAMPLE A 2 TO
4 FOLD INCREASE IN PREVALENCE IN
BLACK CHILDREN.
GREATER SEVERITY OF DISEASE, BUT
THERE THEY'RE ALSO LESS LIKELY O
RECEIVE A T ABDUL T & A AND HAVA
LONGER TIME TO OSA DIAGNOSIS.
CHILDREN FROM LOWER SE SBAC
GROWBDZ ALSO HAVE HIGHER RATES
OF OSA, LESS ACCESS TO T & A AND
LONGER TIME TO OSA DIAGNOSIS.
WE DON'T KNOW AS MUCH ABOUT SEX
AND GENDER DISPARITIES
PARTICULARLY WHEN IT COMES TO
EVIDENCE-BASED CARE.
SO UNLIKE IN THE SLIDE THAT WE
SAW YESTERDAY, LOOKING AT LOW
RATES OF FEMALE PARTICIPATION IN
PAP STUDIES, I DO THINK MOST OF
THE STUDIES INCLUDE FAIRLY
PROPORTIONAL RATES OF MALES AND
FEMALES, HOWEVER, THERE ARE
RELATIVELY FEW THAT EXAMINE
GENDER AS A POTENTIAL PREDICTOR
OF DIAGNOSIS OR CARE.
THERE IS SOME LITERATURE TO
SUGGEST HIGHER PREVALENCE OF OSA
IN BOYS, HIGHER AHI, BUT AS
WE'VE BEEN LEARNING THE LAST TWO
DAYS, SOME OF THAT CAN BE COULD
BE FOUNDED FOUND CONFOUNDED BYE
OF AHI AS A MEASURE AND
POTENTIAL GENDER DIFFERENCES
THERE.
THIS IS ALSO PARTICULARLY THE
CASE FOR BOYS WHO HAVE OBESITY.
HOWEVER, WHEN WE LOOK AT
DELIVERY OF EVIDENCE-BASED CARE,
SO FAR STUDIES HAVE NOT SHOWN
GENDER DISPARITIES IN TERMS OF
WHO GETS REFERRED BY THE PCP,
LIKELIHOOD OF RECEIVING A T & A
AND FOLLOW-UP CARE AFTER A T &
A.
SO ONE OF THE CHALLENGES WITH
PEDIATRIC OSA DETECTION AND
MANAGEMENT IS THERE ARE A LOT OF
STEPS IN THIS PROCESS, RIGHT?
SO TO START OFF WITH, SOMEBODY
HAS TO BE AWARE OF THE SYMPTOMS
AND RISK FACTORS, SO THE FAMILY
HAS TO NOTICE THAT THE CHILD
SENATORS.
THEY HAVE TO RECOGNIZE THAT AS
PROBLEMATIC, AND THERE HAVE BEEN
SEVERAL STUDIES THAT HAVE SHOWN
THAT A NUMBER OF FAMILIES THINK
OF SENATORS AS SOMETHING THAT IS
NORMAL OR CUTE OR SOMETHING
THAT'S OUTGROWN.
IN ADDITION FAMILIES HAVE TO BE
ACTIVATED THEN TO ENGAGE WITH
THE MEDICAL SYSTEM AROUND THE
SYMPTOMS THEY'RE SEEING.
OF COURSE IF WE CAN GET
UNIVERSAL SCREENING, WE DON'T
NECESSARILY NEED THOSE THREE
STEPS, SO THEN WE NEED THE PCP
TO DO AN EVALUATION AND USE
EVIDENCE-BASED DEDISITION
MAKING, APPROPRIATE REFERRAL AND
CARE.
THE FAMILY NEEDS TO ADHERE TO
WHATEVER THAT RECOMMENDATION WAS
AND THEN THERE'S COORDINATION
BETWEEN SYSTEMS, BETWEEN PRIMARY
CARE AND THE LAB AND
SUBSPECIALISTS.
SO THERE ARE A LOT OF
OPPORTUNITIES HERE FOR US TO
LOSE PATIENTS ON THIS PATHWAY.
A COUPLE STUDIES HAVE LOOKED AT
THAT.
SO ONE STUDY THAT LOOKED AT
TREATMENT PATHWAYS BY MINNETH
ALL, DR. WILLIAMSON ON THE CALL
WAS AN AUTHOR ON THIS PROJECT AS
WELL, THEY FOUND THAT CHILDREN
WITH AN OSA DIAGNOSIS THE MOST
COMMON PATHWAY WAS ACTUALLY NO
CARE WITH 34.4% OF CHILDREN.
IN OUR STUDIES WE'VE LACKED AT
PCP ALERTS FOR CHILDREN AT RISK
OF OSA AND WE FIND THAT JUST
OVER HALF OF CHILDREN THAT HAVE
A POSITIVE SC POSITIVE SCREEN FT
RECEIVE CARE SO CLEARLY THERE
ARE MANY MISSED OPPORTUNITIES.
THAT TAKES ME TO IMPLEMENTATION
APPROACHES.
I'M GOING TO FOCUS AT LEAST
WITHIN THE PRIMARY CARE SETTING,
I'M GOING TO FOCUS ON CLINICAL
DECISION SUPPORT SYSTEMS.
SO THIS WAS AN EFFICACIOUS TOOL
TO FACILITATE EVIDENCE-BASED
SCREENING, SURVEILLANCE,
REFERRAL, TREATMENT AND
FOLLOW-UP.
TYPICALLY IT INCLUDES SCREENING
FOR RISK, PROVIDER ALERTS,
WORKFLOW FACILITATION, PATIENT
EDUCATION, AND BY DEFINITION,
CDSS IS TAILORED, AND IT DOES
CONSIDER PERSONALIZED RISK.
SO I THINK THERE'S A LOT OF
OPPORTUNITY HERE.
SO FOR EXAMPLE, YOU COULD HAVE
SEPARATE ALGORITHMS FOR BOYS AND
GIRLS IF THE SCIENCE INFORMS
THAT NEED.
SO TO GIVE YOU AN EXAMPLE, THIS
IS A SYSTEM WE IMPLEMENTED IN MY
INSTITUTION SEVERAL YEARS AGO IN
FIVE PRIMARY CARE CLINICS THAT
SERVE MOSTLY BLACK AND HISPANIC
CHILDREN WITH MEDICAID
INSURANCE.
SO WE ASKED PARENTS IN THE
WAITING ROOM ON A TABLET, DOES
YOUR CHILD USUALLY SENATOR THREE
OR MOWR NIGHTS PER WEEK, AND WE
DID THIS WITH ALL PARENTS.
IF THE PARENT SAID YES, THEN WE
SENT THE PCP A VERY BASIC PROMPT
IN THE ELECTRONIC HEALTH RECORD.
THIS CHILD SENATORS, THIS MIGHT
BE OSA.
SNORES, THIS MIGHT BE
OSA.
WITH THIS SIMPLE INTERVENTION WE
FOUND ALMOST TRIPLE THE RATES OF
BOTH PSG REFERRALS AND
DOCUMENTATION OF SNORING
COMPARED TO THE COMPARABLE TIME
PERIOD PRIOR TO IMPLEMENTATION
OF THE SYSTEM.
HOWEVER, WE ALSO SAW THERE WAS
SIGNIFICANT VARIATION IN
PROVIDER BEHAVIOR IN REGARDS TO
REFERRALS.
YOU CAN SEE ON THE X AXIS, EACH
I.D. REPRESENTS A PROVIDER WHO
RECEIVED AT LEAST FIVE PROMPTS
ABOUT A CHILD HISTORY -- CHILD
WHO SCREENED -- ABOUT A CHILD
WHO SNORES.
HERE YOU SEE THE RATE IN WHICH
THEY THEN REFERRED THE CHILD OR
IDENTIFIED OSA IN THAT CHILD.
SO SOME PROVIDERS FELT A CHILD
HAD OSA, SOME PROVIDERS ACTED
ABOUT TWO THIRDS OF THE TIME.
SO QUITE A BIT OF PRACTICE
VARIATION.
SO WE WANTED TO UNDERSTAND A
LITTLE BIT MORE WHAT FACTORS ARE
PROMPTING THESE DIFFERENTIAL
REFERRAL RATES.
WE LOOKED AT PATIENT DEMOGRAPHIC
FACTORS INCLUDING SEX, PATIENT
HEALTH FACTORS AND THEN PROVIDER
AND CLINIC CHARACTERISTICS.
AND WE FOUND THAT WHILE AGE WAS
SOMEWHAT PREDICTIVE, THE MAIN
PREDICTORS OF WHETHER OR NOT A
CHILD RECEIVED A REFERRAL WERE
RELATED TO THE PROVIDER
CHARACTERISTICS AND NOT, FOR
EXAMPLE, THE PATIENT RISK
FACTORS WHICH WOULD BE
APPROPRIATE.
SORE JUST ANOTHER EXAMPLE OF
CDSS, THIS IS MY K23 WORK FUNDED
BY NHLBI, THANK YOU.
SO THIS INVOLVED SCREENING IN MY
CART ANDCHART AND WE ASKED ABOUT
SNORING.
WIF THE CHILD SCREENED POSITIVE
WE THEN PROVIDED A
NON-INTERRUPTIVE PROVIDER ALERT,
SO YOU CAN SEE HERE THAT IN THE
MENU IT SAYS SCREENED POSITIVE
AND IF THE PROVIDER CLICKS ON
THAT, THEN A BEST PRACTICE
ADVISORY ALERT EMERGES THAT
NOTES THAT THE PATIENT IS AT
HIGHER RISK FOR OSA AND LISTS
PATIENT SYMPTOMS AND RISK
FACTORS, AS WELL AS A VARIETY OF
ACTIONS THAT CAN BE TAKEN.
SO I WANT TO TAKE A STEP BACK
AND TALK ABOUT THE ROLE OF THE
FAMILY IN PRIMARY CARE
IMPLEMENTATION AND OSA
DETECTION.
SO IN TRADITIONAL CDSS, THE
PARENT'S INVOLVEMENT INVOLVES
PROVIDING INFORMATION.
THAT INFORMATION IS THEN GIVEN
TO THE PROVIDER WHO MAY OR MAY
NOT ACT ON THAT INFORMATION
AND/OR TALK TO THAT FAMILY ABOUT
THE INFORMATION.
HOWEVER, THERE IS AN ARGUMENT TO
BE MADE INVOLVING PROVIDERS AND
FAMILIES MORE IN THIS PROCESS
WHEREBY THE FAMILIES PROVIDE
INFORMATION, BUT IF THERE'S A
POSITIVE SCREEN, THE FAMILIES
ARE GIVEN THAT INFORMATION, AND
THEY HAVE THE OPTION TO BRING
THAT INFORMATION TO THE
PROVIDER.
SO THIS IDEA OF PATIENT
ACTIVATION KIND OF LIKE A
PHARMACEUTICAL COMMERCIAL.
SO WE DEVELOPED WITH STAKEHOLDER
FEEDBACK A HEALTH COMMUNICATION
MESSAGE TO ACTIVATE PARENTS
AROUND OSA, IT SAYS BASED OP
YOUR ANSWERS YOUR CHILD MAY HAVE
A SLEEP PROBLEM CALLED SLEEP
APNEA.
IF YOU SEE ANY OF THESE
PROBLEMS, LET YOUR CHILD'S
DOCTOR KNOW.
SO WE WANTED TO LOOK AT THE
IMPACT OF THIS TYPE OF MESSAGING
WITHIN COMPUTER DECISION SUPP
SUPPORT.
SO IF A CHILD SCREENED POSITIVE
FOR OSA THE PARENT WOULD SEE
THIS MESSAGE PRIOR TO THE
CHILD'S APPOINTMENT.
AND THEN WE ASKED PARENTS BASED
ON THIS MESSAGE, DO YOU PLAN TO
TALK TO YOUR CHILD'S DOCTOR
ABOUT SLEEP APNEA TODAY?
JUST UNDER HALF SAID YES.
ABOUT A THIRD WERE UNSURE.
AND ABOUT 22% SAID THEY'RE NOT
PLANNING TO TALK TO THEIR
CHILD'S DOCTOR ABOUT SLEEP
APNEA.
SO THERE WAS A DIFFERENT
RESPONSE, THE MESSAGE RESONATED
MORE WITH SOME FAMILIES THAN
OTHERS.
OF THOSE WHO SAID THEY PLANNED
TO TALK TO THEIR CHILD'S DOCTOR,
MORE THAN HALF OF THOSE CHILDREN
RECEIVED DOCUMENTED OSA
FOLLOW-UP.
SO A NASAL STEROID OR PSG
REFERRAL, WHEREAS THE RATE WAS
CLOSER TO 20% IN CASES WHERE
PARENTS WERE NOT ACTIVATED.
SO I THINK THIS REALLY SPEAKS TO
THE PROMISE OF PATIENT AND
FAMILY ACTIVATION AS AN APPROACH
TO PROMOTE EVIDENCE-BASED
DETECTION AND CARE.
THERE ARE ALSO SOME STUDIES THAT
HAVE LOOKED AT COMMUNITY AND
OTHER SETTINGS AS A WAY TO
SCREEN AND BRING PARENTS INTO
THE PRIMARY CARE SETTING.
THEY DID A STUDY WHERE THEY
ADMINISTERED THE PEDIATRIC SLEEP
QUESTIONNAIRE AT SEVEN HEAD
START CLINICS AND FAMILIES
RECEIVE WRITTEN INFORMATION AND
HELP WITH REFERRALS.
WE CONDUCTED A STUDY WHERE WE
HAD PARENTS COMPLETE THE
PEDIATRIC SLEEP QUESTIONNAIRE.
WE ALSO HAD TEACHERS COMPLETE
THE PSQ BASED ON THEIR
OBSERVATION OF CHILDREN NAPPING.
WE NOTIFIED FAMILIES OF A
POSITIVE SCREEN, GAVE THEM A
LETTER TO TAKE TO THEIR PCP AND
AN INFORMATIONAL MESS J A, AND F
THOSE THAT RECEIVED THAT
INTERVENTION, ALMOST ALL
CONTACTED THEIR PCP AND ABOUT
60% RECEIVED APPROPRIATE CARE
INITIALLY.
I THINK THERE'S ALSO SOME
IMPORTANT WORK AROUND CARE
NAVIGATION, SO THIS IS A STUDY
THAT'S ONGOING THAT LOOKS AT
PRIMARY CARE SLEEP NAVIGATION
FOR CHILDREN WHO HAVE BEEN
REFERRED TO SPECIAL CARE TO HELP
THEM SUCCESSFULLY COMPLETE THAT
PATHWAY AND COORDINATE CARE AND
THIS IS BEING CONDUCTED BY
AERIAL WILLIAMSON AND
COLLEAGUES, SO EAGER TO SEE
THOSE RESULTS.
SO IN SUMMARY, I THINK WE HAVE A
REALLY IMPORTANT GAP REGARDING
INSUFFICIENT RATES OF
EVIDENCE-BASED DETECTION AND
CARE FOR PEDIATRIC OSA.
SO I THINK ONE OF THE THINGS FOR
ME THAT THIS WORKSHOP HAS
ILLUSTRATED IS THERE'S A LOT
THAT WE DON'T KNOW ABOUT
EVIDENCE-BASED TREATMENT AND
ADDRESSING HETEROYES NATE AND HD
PERSONALIZED TREATMENT.
WE HAVE A LOT TO LEARN.
AT THE SAME TIME THERE'S A LOT
THAT WE ALREADY KNOW AND WE WANT
TO MAKE SURE THAT'S GETTING TO
THE PATIENTS WHO NEED IT.
I THINK SOME GAPS RELATED TO
THIS, THERE'S NOT ENOUGH DATA ON
SEX AND GENDER AND HOW THAT
INFLUENCES DETECTION AND CARE.
UNIVERSAL SCREENING IS
RECOMMENDED BUT DOESN'T OCCUR.
THERE'S UNWARRANTED PRACTICE
VARIATION AND THERE ARE
BOTTLENECKS, BARRIERS AND MISSED
OPPORTUNITIES IN THE CARE
PATHWAY.
SO IF WE GO BACK TO THINKING
ABOUT THIS PATHWAY, I THINK
THERE'S SOME INTERVENTIONS THAT
CAN BE HELPFUL AT VARIOUS
STAGES.
SO TECHNOLOGY LIKE WEARABLES OR
BABY CAMERAS COULD MAKE PARENTS
AWARE OF SYMPTOMS ORIS BEING
FACTORS.
HEALTH COMMUNICATION MESSAGING
CAN HELP FAMILIES RECOGNIZE THAT
SYMPTOMS ARE A PROBLEM AND
ACTIVATE THEM TO TALK TO THEIR
PROVIDER.
UNIVERSAL SCREENING AT THE PCP
LEVEL, CLINICAL DECISION
SUPPORT, ALSO FAMILY ACTIVATION
AFTER THE REFERRAL, AS WELL AS
COORDINATION TO HELP FAMILIES
WHO ARE REFERRED COMPLETE THOSE
STEPS.
SO JUST TO SUMMARIZE, I THINK
SOME NICE OPPORTUNITIES ARE KIND
OF WEARABLES TO IDENTIFY RISK OR
TECHNOLOGY, AUTOMATED SCREENING,
SCALABLE CLINICAL DECISION
SUPPORT TOOLS POSSIBLY WITH
GENDER-SPECIFIC ALGORITHMS,
LEARNING MORE ABOUT PATIENT AK
VAITION SUPPORTING PATHWAYS TO
KAI AND YOU CAN SEE SOME OF THE
DISCIPLINES AND FRAMEWORKS THAT
I THINK COULD BE HELPFUL IN
THESE ENDEAVORS.
YOU THAT.
>> THANK YOU VERY MUCH FOR THIS
INTERESTING TALK ON PRIMARY CARE
AND IMPLEMENTATION OF PEDIATRIC
OSA AND STRIKING LOW RATES OF
UNDERDIAGNOSIS AND TREATMENT
LOOK BEING FORWARD TO DISCUSSION
LATER ON FOR THE CLINICAL
APPROACHES YOU DESCRIBED.
MOVING ON TO OUR THIRD SPEAKER,
OUR THIRD SPEAKER IS DR. SUZANN
BERTISCH, CLINICAL DIRECTOR OF
BEHAVIORAL SLEEP AT BRIGHAM'S
WOMEN HOSPITAL AND ASSISTANT
PROFESSOR AT HARVARD MEDICAL
SCHOOL.
HER TALK IS ENTITLED
INCORPORATING DISSEMINATION AND
IMPLEMENTATION SCIENCE IN SLEEP
CLINICAL TRIALS.
THE MICROPHONE IS YOURS.
>> THANK YOU SO MUCH FOR HAVING
ME.
I JUST WANT TO MAKE SURE, IT
LOOKS LIKE MY SLIDES ARE SHOWING
A LITTLE BIT FUNKY, SO LET ME
GET THEM --
>> YOU'RE HAVING THE SAME
PROBLEM I HAD.
>> HERE WE GO.
OKAY.
SORRY.
THANK YOU SO MUCH FOR HAVING ME.
I THINK I'M THE LAST SPEAKER OF
THE CONFERENCE, SO THANK
EVERYBODY FOR STAYING, STICKING
AROUND FOR OUR LAST SESSION ON
IMPLEMENTATION SCIENCE.
I'M REALLY EXCITED THAT THIS
SESSION WAS INCLUDED BECAUSE
IT'S NEAR AND DEAR TO A LOT OF
THE WORK WE DO.
I DO RECEIVE CONSULTING FEES
FROM INDUSTRY BUT I HAVE NO
ACTUAL CONFLICT OF INTEREST IN
RELATION TO WHAT I'M SPEAKING ON
TODAY.
I KNOW DR. TOBIN GAVE A NICE
OVERVIEW AND I WILL JUST TOUCH
ON SOME POINTS BRIEFLY.
SO AT THE BEGINNING AND
THROUGHOUT THE TALK AS WELL.
THEN WE'LL TALK ABOUT SOME OF
THE APPROACHES AND EXAMPLES
SPECIFIC TO THE SLEEP LITERATURE
WITH IMPLEMENTATION SCIENCE HAS
BEEN LEVERAGED TO IMPROVE THE
SCIENCE AND I'LL WRAP UP WITH
SOME KEY POINTS AND THEN WE'LL
OPEN FOR DISCUSSION AT THE END.
SO ALREADY TALKED ABOUT TODAY,
THE REAL GOAL OF IMPLEMENTATION
SCIENCE IS A METHODOLOGY TO TAKE
WHAT WE KNOW FROM OUR RESEARCH
IN OUR CLINICAL RESEARCH FINDING
AND BRING TO THE BEDSIDE TO THE
PATIENT TO THE COMMUNITY AND
REALLY INFORM WHAT WE DO.
AND I THINK IMPLEMENTATION
SCIENCE IS THE TOOLBOX THAT
REALLY GIVES US AN ARRAY OF
TOOLS TO FIGURE OUT THE HOW AND
HOW CAN WE ACTUALLY OVERCOME
THIS GAP OF EFFECTIVE TREATMENTS
FOR SLEEP APNEA BUT HOW DO WE
ACTUALLY GET THEM TO THE HANDS
OF OUR PAITION OR AT THE
BEDSIDES AND USE THEM MORE
READILY IN THE CLINIC?
AS WAS TALKED ABOUT ACTUALLY
EARLIER, YESTERDAY, SHE HAD THIS
ON ONE OF HER SLIDES.
IT'S IMPORTANT TO NOTE THAT
IMPLEMENTATION SCIENCE IN
GENERAL CLOSELY ALIGNS TO -- IN
WHAT WE'VE TALKED ABOUT TODAY,
PRINCIPLES OF EQUITY, WHICH IS
DEFINED AS GIVING EVERYONE A
FAIR AND JUST OPPORTUNITY TO BE
AS HEALTHY AS POSSIBLE.
AND THE FIELD OF IMPLEMENTATION
SCIENCE CAN HELP US ADDRESS
THESE INEQUITIES BY HELPING US
STUDY THE FACTORS, PROCESSES AND
STRATEGIES AT MULTIPLE LEVELS OF
A SYSTEM OF CARE THAT INFLUENCED
THE UPPER TAKE, UP TAKE, USE ANY
SUSTAINABILITY OF OUR
EVIDENCE-BASED INTERVENTIONS AS
WELL AS POLICIES IN DIFFERENT
COMMUNITY AND PRACTICE SETTINGS.
SO JUST AS AN EXAMPLE I THINK
ABOUT IN SLEEP RESEARCH, THERE
ARE SEVERAL DIFFERENT CLINICAL
PRACTICE GUIDELINES.
I JUST PULLED ONE OF THE MORE
RECENT ONES FOR THE AMERICAN
THORACIC SOCIETY IN WHICH THE
GUIDELINES RECOMMENDS
PARTICIPATION IN A COMPREHENSIVE
LIFESTYLE INTERVENTION PROGRAM
FOR WEIGHT MANAGEMENT AND
TREATMENT OF OBSTRUCTIVE SLEEP
APNEA.
HOWEVER WHAT THE GUIDELINE
DOESN'T TELL US IS HOW WE
ACTUALLY USE THIS IN OUR
CLINICAL SETTINGS SO THERE'S NO
ROAD MAP ON HOW TO DISSEMINATE
AND BROADLY IMPLEMENT THESE
GUIDELINES.
THE OTHER ISSUE IS THAT ASSUMING
THAT ALL OF THESE TREATMENTS
WILL IMPROVE NOT JUST THE
QUALITY BUT ALSO COST AND SYSTEM
OUTCOMES, ONCE THEY'RE
DISSEMINATED, OVERLOOKS, AGAIN,
SOME OF THE FACTORS WE'VE HEARD
ABOUT IN THE OTHER TWO TALKS IN
THIS SESSION, IS THAT THE
CONTEXT IN WHICH WE DELIVER
THESE TREATMENT STRATEGIES ARE
REALLY IMPORTANT, SO WE'VE
TALKED A LOT IN THE LAST FEW
DAYS ABOUT THE SEX AND GENDER
DIVERSITY OF THE SLEEP APNEA
POPULATION, BUT THERE'S ALSO
DIVERSITY OF PROVIDERS IN THE
SETTINGS OF WHICH WE DELIVER THE
INTERVENTION AND IT'S UNLAKELY
THAT THE SAME STRATEGIES CAN BE
IMPLEMENTED SUCCESSFULLY ACROSS
THE CONTEXT.
MENTIONED ALREADY, THIS IS
REALLY MORE THAN BECAUSE WE KNOW
SLEEP APNEA IS A VERY DIFFERENT
DISEASE, WHETHER ENDOTYPE OR
PHENOTYPE AND EVEN WHAT IT LOOKS
LIKE IN THE FACES IN OUR CLINIC.
IN LIGHT OF THIS, IT'S IMPORTANT
FOR US AS A FIELD TO EVEN START
ASKING MORE QUESTIONS.
AGAIN THERE'S BEEN A LOT OF
QUESTIONS TODAY ABOUT ENDOTYPES
AND PHENOTYPES AND SEX AND
GENDER, BUT ALSO OTHER QUESTIONS
TA WE'LL SORT OF PEPPER IN AND
TALK ABOUT HOW WE CAN THINK OF
THIS AND ALSO TO URGE PEOPLE AND
THINK ABOUT THIS EARLIER ON IN
THE TRANSLATIONAL SPECTRUM, AND
HOW DO WE ACTUALLY THINK ABOUT
CONSIDERING SEX AND GENDER
DIFFERENCES AND DEVELOPING OUR
INTERVENTIONS, ALSO HOW DO WE
MEASURE AND ANALYZE THE EFFECTS
OF SEX AND GENDER ON SLEEP APNEA
OUTCOMES AND THEN DOWN THE LINE
IN THE FUTURE, ON IMPLEMENTATION
OUTCOMES.
SO WHAT ARE SOME EXAMPLES OF
BARRIERS TO IMPLEMENTATION?
SARAH JUST TALKED A LOT ABOUT
THIS, THE BARRIERS TO PEDIATRIC
SLEEP APNEA IN THE PRIMARY CARE
SETTING BUT ALSO TALK A LITTLE
ABOUT WHY WE SHOULD CONSIDER THE
SEX AN AND GENDER DIFFERENCES.
SO EVEN IF WE HAVE A TREATMENT
THAT'S 100% EFFICACIOUS, YOU CAN
ALMOST THINK ABOUT SOMETHING --
CPAP IS ACTUALLY NEARLY
EFFICACIOUS RIGHT IN THE IDEAL
SETTINGS, BUT WHERE IT DROPS --
WHERE THE VOLTAGE DROPS, THE
EFFECTS OF CPAP ARE DONE BECAUSE
WE HAVE LIMITATIONS ON THE
INDIVIDUAL PATIENT LEVEL ABOUT
PEOPLE DON'T ADOPT IT, IT'S NOT
ACCEPTABLE TO SOME PATIENTS,
THEN OTHER THINGS THAT
INTERFERE, EVEN IF THINGS ARE
ARE 100% EFFECTIVE, THE IMPACT
ALSO DEPENDS ON THE FIDELITY OF
THE INTERVENTION AS WELL AS THE
FEASIBILITY AND APPROPRIATENESS,
AND THAT SOME OF THE QUESTIONS
YOU THINK ABOUT, IS IT
APPROPRIATE FOR EVERYBODY, HOW
THIS ACTUALLY MAY VARY BY SOME
OF THE BOTH BIOLOGICAL AS WELL
AS SOCIAL FEATURES AS WELL.
EVEN IF AN INTERVENTION IS 100%
EFFECTIVE, SO IT BEEN SHOWN TO
BE EFFECTIVE IN THE REAL WORLD,
ITS IMPACT IS ALSO DIMINISHED BY
WE CAN THINK ABOUT MORE SYSTEM
FACTORS.
OUR SYSTEM IS GOING TO ADOPT
THESE PRACTICES, CAN WE TRAIN
PRACTITIONERS TO DELIVER THESE
INTERVENTIONS AND THEN CAN THEY
ACTUALLY DELIVER IT WITH
FIDELITY AS WELL.
ARE WE GIVING PATIENTS ACCESS TO
TREATMENT, IF WE THINK ABOUT
PATIENTS ACCESS TO TREATMENT AT
A POPULATION LEVEL, CAN THESE
INTERVENTIONS BE SUSTAINED OVER
TIME.
SO THESE ARE ALL THINGS THAT
AGAIN THE FIELD OF
IMPLEMENTATION SCIENCE SOMETIMES
REFER TO AS THE VOLTAGE DROP,
THAT AS WE TAKE SOMETHING FROM
THE CONTROLLED CLINICAL TRIAL
SETTINGS, THEY HAVE LESS
EFFECTIVENESS IN THE REAL WORLD
DUE TO A VARIETY OF FACTORS
INCLUDING PATIENT HETEROGENEITY.
SO THIS IS THE SLIDE THAT
DR. REDLINE SHOWED IN ONE TALK
IN THINKING ABOUT HOW SEX AND
GENDER PERMEATE EACH LEVEL OF
SLEEP APNEA THINKING ABOUT BOTH
SOCIETAL, INS TAWTIONAL, IN
ADDITION HOUSES AND INDIVIDUAL
DIFFERENCES BUT IT'S ALSO
IMPORTANT TO THINK ABOUT HOW
THESE FACTORS ALSO IMPACT OUR
ABILITY TO ADAPT AND SUSTAIN
TREATMENT.
AGAIN THIS IS IS GOING BACK TO
THE CONTEXTUAL FACTORS AND EVEN
IF WE FOCUS ON THE INDIVIDUAL
LEVEL FACTORS, WE KNOW THAT THE
CONTEXT IS ULTIMATELY GOING TO
IP FLTOINFLUENCE IMPLEMENTATION.
SEX AND GENDER ROLES ARE OFTEN
VERY INTERWOVEN TO THE FABRIC OF
SOCIAL, ECONOMIC, EVEN
BIOLOGICAL FACTORS, AND WE
SHOULD CONSIDER OW SEX AND
GENDER BEYOND JUST A LOT OF THE
BIOLOGY TALKED ABOUT TODAY,
ABOUT HOW SEX AND GENDER ROLES,
IDENTITY RELATIONS AND
INSTITUTIONALIZED GENDER
INFLUENCE THESE FACTORS AT A
VARIETY OF LEVELS.
SO WE SHOULD CONSIDER ASKING
QUESTIONS SUCH AS, YOU KNOW, IN
THINKING ABOUT, FOR EXAMPLE,
DIAGNOSIS AND TREATING SLEEP
APNEA, AGAIN, WE SHOULD BE
ASKING QUESTIONS BEYOND THE
BIOLOGY THAT INFLUENCED REAL
WORLD PRACTICE AND HOW CAN WE
CONSIDER GENDER ROLES HELPING US
TO UNDERSTAND AND ANTICIPATE
BARRIERS AND OPPORTUNITIES
FACING HEALTHCARE PROFESSIONALS
AND UPTAKE OF NEW INTERVENTIONS.
SO ONE EXAMPLE IS CLINICALLY AS
A PHYSICIAN, I'VE HAD NUMEROUS
PATIENTS WHO IDENTIFY AS FEMALE
OVER THE YEARS SAY THAT THEY'VE
DELAYED IN ACCESSING CARE FOR
SLEEP APNEA BECAUSE OF STIGMA
RELATED TO BODY WEIGHT AND BEING
AN UNHEALTHY -- THAT AFFECT
WOMEN AS WELL, WE'VE HEARD
EARLIER THAT YOUNGER WOMEN
ACTUALLY HAVE THE LOWEST RATES
OF CPAP TO ADHERENCE.
SO AGAIN, THERE'S SEX AND GENDER
ISSUES.
AND ALSO THINKING ABOUT A
PARTICULAR DECISION-MAKING
GROUP, AGAIN THESE ARE PEOPLE
WHO INFLUENCE THE ADOPTION OF
POLICIES, HOW WE MIGHT ACTUALLY
CONSIDER INSTITUTIONALIZED
GENDER.
THIS IS JUST AN EXAMPLE, MAYBE
MORE SUBTLE, IN MY OWN PRACTICE
WE HAVE MANNEQUINS OF VARIOUS
MASKS IN THE CLINIC BUT AGAIN,
THEY'RE ALL MANNEQUINS, THEY'RE
ALL REPRESENTATIONS OF MALE
FIGURES WEARING CPAP.
NONE OF MY FEMALE PATIENTS
ACTUALLY HAVE ANY EXAMPLES OR
VISUALS OF WOMEN WITH CPAP IN
OUR CLINICAL SPACE.
SO AGAIN, THAT'S MAYBE A SORT OF
AN IMPLICIT BIAS TOWARDS WHOEVER
PURCHASED THE MANNEQUIN FOR OUR
CLINIC, BUT IT'S IMPORTANT TO
THINK ABOUT HOW BOTH ON AN
INDIVIDUAL PRACTICE LEVEL AND
EVEN IPS TEUTIONALLIZE HOW SEX
AND GENDER ROLES MAY ACTUALLY
EVENTUALLY INFLUENCE OUR ABILITY
TO TREAT THE VARIETY OF PATIENTS
WE SEE IN SLEEP APNEA.
AND AGAIN, ONE EXAMPLE IS HOW DO
WE CONSIDER GENDER WHEN ROLLING
OUT PAP EDUCATION MATERIALS AND
PROGRAMS.
SO THE NEXT PART OF THE TALK,
I'M GOING TO FOCUS BRIEFLY ON
SHOWING EXAMPLES OF HOW
DIFFERENT RESEARCHERS HAVE
LEVERAGED IMPLEMENTATION SCIENCE
AGAIN ACROSS THE TRANSLATIONAL
STUDY.
SO THE FIRST EXAMPLE IS TO SHOW
PATIENTS LEVERAGING
IMPLEMENTATION SCIENCE.
I'M GOING TO SORT OF SUMMARIZE
SOME OF THE CORE ELEMENTS THAT
SORT OF ARE CONSISTENT ABOUT
STUDIES AND HOW WE'VE BEEN ABLE
TO LEVERAGE THIS ROBUST
METHODOLOGY.
SO SOME OF THE CORE ELEMENTS
INCLUDE USING DIFFERENT
THEORIES, MODELS AND FRAME WORKS
TO DESIGN STUDIES AND TO THINK
ABOUT COLLECTING OUTCOMES AND
IMPLEMENTING THE STUDIES
THEMSELVES.
STAKEHOLDER COLLABORATOR
ENGAGEMENT.
SELECTION OF INTERVENTIONS,
EVALUATION MEASURES AND AS WELL
AS IMPLEMENTATION STRATEGIES.
WHICH WE'LL TALK ABOUT IN A BIT.
THIS REALLY DESCRIBES AN ATTEMPT
TO GUIDE RESEARCHERS THINKING
ABOUT IMPLEMENTATION STUDIES OF
EVIDENCE-BASED INTERVENTIONS.
SO THE FIRST PART WHEN YOU'RE
SORT OF APPROACHING AND THINKING
ABOUT WHERE IS MY RESEARCH ON
THE IMPLEMENTATION SCIENCE
SPECTRUM IS TO IDENTIFY A
PRACTICE OF INTEREST.
THIS IS AN EVIDENCE-BASED
PRACTICE.
IT CAN BE A PROCEDURE, IT CAN BE
A GUIDELINE, IT CAN BE A
PRACTICE CARE PATHWAY, AND THE
FIRST QUESTION TO ASK IS, DOES
THIS -- IS THIS POI EFFICACIOUS.
SO IS THERE EFFICACY.
AND THEN IF THE ANSWER IS NO,
THEN YOU'RE GOING TO DESIGN YOUR
RESEARCH ALONG THIS RED PATHWAY.
IT'S IMPORTANT TO KEEP IN MIND
EVEN THOUGH THIS EFFICACY
RESEARCH IS NOT YET IN THE
YELLOW OR GREEN ZONE WHERE WE
REALLY START TO DEFINE
IMPLEMENTATION RESEARCH, AS
DR. TOBIN POINTED OUT, YOU COULD
DESIGN FOR IMPLEMENTATION OR FOR
DISSEMINATION IN MIND.
AGAIN, IF YOU HAVE A VERY
COMPLICATED, CLUNKY IP
INTERVENTION, IT'S JUST NOT
GOING TO MAKE IT OUT IN THE REAL
WORLD SETTING, SO IT'S IMPORTANT
TO THINK ABOUT THESE PRINCIPLES.
SO DR. WILLIAMSON, THIS IS SORT
OF AN EXEMPLAR MODEL DESIGNING
FOR DISSEMINATION IMPLEMENTATION
IN MIND WHEN SHE WAS DEVELOPING
AND ADAPTING BEHAVIORAL
INTERVENTIONS FOR YOUNG CHILDREN
OF LOW SES OR RACIAL/ETHNICALLY
MINORITIES BACKGROUNDS AGAIN IN
THE PRIMARY CARE SETTING AND AS
A FIRST STEP RATHER THAN SAYING
HERE'S THE INTERVENTION I WANT
TO IMPLEMENT IN THIS SPACE,
REALLY WHEN SPOKE WITH
CAREGIVERS OF FAMILY MEMBERS,
CAREGIVERS OF THESE KIDS,
PATIENT CLINICIANS, HAVING AN
ADVISORY BOARD, SPEAKING TO
PRIMARY CARE STAFF AND
UNDERSTANDING WHAT WOULD
ACTUALLY WORK IN THIS
INTERVENTION, SO SHE USED THIS
TO IDENTIFY NOT JUST THE
INTERVENTION CONTENT BUT ALSO
WHAT ARE THE IMPLEMENTATION
STRATEGIES I CAN CONSIDER USING
DOWN THE LINE AND THEN WENT
THROUGH AN ITERATIVE PROCESS TO
REFINE BOTH THE CONTENT AND THE
IMPLEMENTATION OF THE CONTENT
AND ACTUALLY GAIN INSIGHTS TO
HOW THIS MIGHT BE IMPLEMENTED
FOR FUTURE STUDIES AND THEN
EFFICIENTLY TESTED IN AGAIN A
HYBRID EFFECTIVENESS
IMPLEMENTATION, WHICH DR. TOBIN
REFERRED TO BUT WE'LL TALK ABOUT
MORE.
SO WHEN WE THINK ABOUT MOVING
DOWN THAT INTO THE YELLOW LINE
WHEN SOMETHING IS EFFICACIOUS,
THEN WE CAN MOVE INTO
EFFECTIVENESS, WHERE WE BRING
THINGS INTO THE REAL WORLD TO
SEE DO THEY WORK ACROSS
DIFFERENT POPULATIONS.
AND SITTING BETWEEN THAT T3 AND
T4 ARE THE HYBRID DESIGNS.
THE HYBRID IS THE MIX OF THE
EFFECTIVENESS AND IMPLEMENTATION
RESEARCH.
THIS IS THE SAME FIGURE THAT WE
JUST SAW ABOUT HALF AN HOUR AGO,
WHERE THESE -- AND THESE HYBRID
TRIALS BLEND EFFECTIVENESS
TRIALS WITH IMPLEMENTATION
TRIALS, SO AGAIN, THE HYBRID RUN
IS RELITTLE TESTING
EFFECTIVENESS, THEY'RE DESIGNED
LIKE TYPICAL COMPARATIVE
EFFECTIVENESS STUDY BUT
OBSERVING THE IMPLEM TEATION TO
INFORM HOW WHEN I USE THIS --
WHEN AT THE END OF THE STUDY HOW
AM I GOING TO IMPLEMENT IT, AND
IT'S A REALLY EFFICIENT DESANE
BECAUSE IF YOU'RE DOING
IMPLEMENTING A TRIAL IN THE
CONTEXT WHERE IT WILL BE
DELIVERED, WHY NOT COLLECT GOOD
INFORMATION ABOUT HOW IT MAY
WORK GOING FORWARD.
AT THE OTHER END OF THE
SPECTRUM, THE HYBRID 3 TRIALS
REALLY ARE OBSERVING
EFFECTIVENESS AND TESTING THE
IMPLEMENTATION STRATEGY.
SO WE HAVE THE CURRENT NHLBI
FUNDED HYBRID EFFECTIVENESS,
IT'S A HYBRID 1 EFFECTIVENESS
IMPLEMENTATION TRIAL EVALUATING
BEHAVIORAL TREATMENTS FOR
INSOMNIA AMONG SOCIOECONOMICALLY
DISADVANTAGED ADULTS IN THE
PRIMARY CARE SETTING, AND THIS
I'M NOT GOING TO TALK TOO MUCH
ABOUT OUR TRIAL BUT OUR SPECIFIC
AIMS ARE REALLY SET UP LIKE
TYPICAL COMPARATIVE
EFFECTIVENESS STUDY WHERE WE'RE
COMPARING TWO DIFFERENT
BEHAVIORAL TREATMENTS, ONE IS A
BRIEFER FORM OF COGNITIVE
BEHAVIORAL THERAPY, THE OTHER IS
IS TRADITIONAL COGNITIVE
BEHAVIORAL THERAPY DELIVERED BY
TELEPHONE TO IMPROVE ACCESS IN
THIS TARGET POPULATION OF
INTEREST AND WITHIN THE PRIMARY
CARE SETTING, WITH A
NON-INFERIORITY AIM COMMON IN
THESE TRIALS.
SO THE OUTCOMES OF THIS AIM
WHERE WE'RE REALLY COMPARING
QUALITY OF LIFE AND OTHER
SYMPTOMS, THESE AGAIN ARE SET UP
LIKE COMMON EFFECTIVENESS
STUDIES AND AS WE TALKED ABOUT,
TO THINK ABOUT HOW IT'S
IMPORTANT TO TAKE THE NEXT STEP
IN MOVING TO THE REAL WORLD IS
THINKING ABOUT EXPLORING THAT
HETEROGENEITIMENT WE TALKED A
LOT ABOUT THIS CONFERENCE, HOW
MIGHT THESE OUTCOMES VARY BY OSA
ENDOTYPES AND PHENOTYPES, HOW
ARE SOME OF THESE DIFFERENCES
EXPLAINED BY SEX AND GENDER
DIFFERENCES, BUT I THINK WHERE
SOME OF THE IMPLEMENTATION
SCIENCE COMES IN IS REALLY
THINKING ABOUT THE CONTEXT
THEY'RE DELIVERED, HOW MIGHT SEX
AND GENDER ROLES SUCH AS
OCCUPATION, BREAD WINNER STATUS,
TIME DOING HOUSEHOLD CHORES AND
CAREGIVING RESPONSIBILITIES,
ALSO INFLUENCE THE OUTCOMES THAT
ACTUALLY ARE REAL WORLD BARRIERS
AND SOMETIMES FACILITATORS THAT
MAY RESULT IN SOME OF THE
VARIATION WE SEE ACROSS SEX AND
GENDERED GROUPS.
THE REAL INNOVATIVE PARTS ARE
THESE IMPLEMENTATION AIMS OR
WHERE THEY FORMALLY EMBED THEM
INTO THE STRUCTURE.
FOR OUR STUDY OUR AIM 2 IS TO
EVALUATE THE BARRIERS,
FACILITATORS AND RECOMMEND --
RECOMMENDATIONS FOR BEHAVIORAL
TREATMENT OF INSOMNIA
IMPLEMENTATION AND PRIMARY CARE.
SO HERE WE'RE USING ONE OF A
VERY HEAVILY FRAMEWORK CALLED
THE CONSOLIDATED PRAIM QORK,
WHICH WE ARE GOING TO CONDUCT
INTERVIEWS WITH STAKEHOLDERS
INCLUDING PATIENTS, CLINICIANS,
MEDICAL DIRECTOR ADMINISTRATORS
AND STAFF AS WELL AS SOME OTHER
QUANTITATIVE WORK TO REALLY
START THINKING ABOUT IF THIS --
IF BBTI IS NOT INFERIOR TO CBTI,
HOW DO WE ACTUALLY START
IMPLEMENTING THIS AND EMBEDDING
IT IN PRIMARY CARE IN A WAY THAT
ACTUALLY WORKS.
AND THEN ADDING AGAIN SOME OF
THESE HYBRID OUT COME TRIALS OF
IMPLEMENTATION ADOPTION, PEOPLE
ARE GOING TO USE IT, IS IT
APPROPRIATE FOR THE POPULATION,
IS IT FEASIBLE, CAN WE DELIVER
IT WITH FIDELITY AS WELL AS CO
COST.
AGAIN E IT'S IMPORTANT TO THINK
ABOUT HOW THIS MAY BE LAYERED
WITH DIFFERENT SEX AND GENDER
ISSUES, HOW THE REACH MIGHT VARY
BY MALE, FEMALE OR TRANSGENDER
INDIVIDUALS, SHOULD THE
IMPLEMENTATION, THE INTERVENTION
CAN CONSIDER GENDER IDENTITY OR
SEXUAL ORIENTATION, AND YOU KNOW
EARLIER YESTERDAY WE WERE
TALKING ABOUT PREGNANT PEOPLE
AND PEOPLE WHO ARE
PERIMENOPAUSAL AND MENOPAUSAL
PEOPLE, AND AGAIN IF WE THINK
ABOUT IMPLEMENTING SOME OF THE
SLEEP APNEA TREATMENTS AND
PROTOCOLS AND NOT JUST IN
PRIMARY CARE CLINICS, OB-GYN,
HOW MIGHT THE MESSAGES AND
PROCEDURES AND IMPLEMENTATION
MIGHT DIFFER.
SO AS WE START MOVING ALONG THE
PIPELINE, WE TALKED ABOUT
EFFICACY RESEARCH, WE TALKED
ABOUT A HYBRID EFFECTIVENESS
IMPLEMENTATION TRIAL BUT REALLY
MOVING INTO THE MEATY PART OF
THE SUBWAY LINE AND TALK ABOUT
THE REAL IMPLEMENTATION
RESEARCH, WE TALK ABOUT MIXED
METHODS TO REALLY START
UNDERSTANDING THE CONTEXT AND
THEN DESIGNING IMPLEMENTATION
AND TESTING IMPLEMENTATION
STRATEGIES FOR REAL WORLD USE.
JUST TO QUICKLY SUMMARIZE SOME
OF THE PRINCIPLES DR. TOBIN
REFERRED TO THAT WE APPLY THESE
FRAME WORKS AND THESE ARE
PROPOSED MODEL OF FACTORS THAT
LIKELY IMPACT THE IMPLEMENTATION
SUSTAINABILITY OF EVIDENCE-BASED
PRACTICES, AND THEN WE USE THESE
FRAME WORKS TO IDENTIFY FACTORS
THAT HELP US TO SELECT THE RIGHT
STRATEGY OR STRATEGIES TO USE
DURING THE IMPLEMENTATION
PROCESS.
THESE IMPLEMENTATION STRATEGIES
ARE THEN USED TO ADOPT OR
INTEGRATE THE EVIDENCE-BASED
INNOVATIONS INTO CARE.
SO WE USE THE MODELS TO IDENTIFY
THE FACTORS THAT ARE THEN GOING
TO HELP US TO SELECT THE RIGHT
STRATEGIES OR AS JEFF CURR.
A N SAYS, WHAT ARE WE GOING TO
DO TO MAKE PEOPLE DO THE THING?
AND THESE CAN BE CONCEPTUALIZED
OR CLASSIFIED IN DIFFERENT WAYS.
ONE NOMENCLATURE REFERS TO THEM
AS PLANNING STRATEGIES,
EDUCATIONAL STRATEGY, FINANCIAL,
RESTRUCTURING, QUALITY
MANAGEMENT OR POLICY STRATEGIES.
SO IT'S REALLY COLLECTING
INFORMATION ABOUT HOW TO GET
PEOPLE BEST TO DO THE THING AND
IT'S OFTEN ADVISED TO USE MORE
THAN ONE STRATEGY.
AND THERE IS A CURRENT STUDY
GOING ON FUNDED THROUGH THE V.A.
SYSTEM IN WHICH YOU'RE TRYING TO
IMPROVE THE DIAGNOSIS AND
TREATMENT OF SLEEP APNEA AND
TREATMENT WITH PAP AMONG
PATIENTS WITH STROKE, AND THIS
IS TO INFLUENCE GUIDELINE
CONCORDANT CARE WITHIN THE V.A.,
AS WE KNOW THAT SINCE THESE
GUIDELINES HAVE COME OUT,
THEY'VE ACTUALLY SEEN NOT ONLY
LOW BUT ACTUALLY NO CHANGE IN
SLEEP STUDY UTILIZATION FOR
PATIENTS IN THE V.A. SYSTEM WHO
HAD A STROKE AND TIA EVEN WITHIN
A YEAR OF HAVING THE EVENT.
SO ESSENTIALLY THEIR GUIDELINES
RECOMMENDING TO DO SLEEP TESTING
AMONG THESE INDIVIDUALS, BUT
IT'S NOT HELPING.
AND SO THIS WORK IS LED BY JASON
SICO, WHO'S BASED IN THE V.A.
CONNECTICUT HEALTHCARE SYSTEM,
AND THEY ARE FUNDED IN THEIR
STUDY CALLED ASAP TO UTILIZE
RANDOMIZED TRIAL ACROSS SIX AP
VA MEDICAL CENTERS TO IMPLEMENT
AND EVALUATE THE EFFECTIVENESS
AND SUSTAINABILITY OF
IMPLEMENTATION STRATEGIES TO
IMPROVE THE DIAGNOSIS OF SLEEP
APNEA MANAGEMENT.
SO THE THING THAT THEY'RE
ACTUALLY TESTING IS A SYSTEMS
REDESIGN VIRTUAL COLLABORATIVE
AND DATA MONITORING, SO IT'S
ACTUALLY TRACKING HOW MANY
PEOPLE ARE GETTING TESTED, ARE
THEY USING CPAP AND MONITORING
THAT DATA, AND THEN THEY'RE ALSO
TESTING HOW TO GET PEOPLE TO DO
THE THING, AND THEY'RE LOOKING
AT, AGAIN, IMPLEMENTATION
STRATEGIES SUCH AS LOCAL
ADAPTATION, CHANN CHAMPIONS, EXL
FACILITATION, AUDIT AND
FEEDBACK.
AND THEY'RE LOOKING AT
DIFFERENT -- THEIR OUTCOMES ARE
IN DIFFERENT LEVELS, THEY'RE
LOOKING AT FACILITY DIAGNOSIS
RATES, 90-DAY RECURRENCE OF
VASCULAR EVENTS, TREATMENT
RATES, PAP ADHERENCE AND 90-DAY
MORTALITY.
SO THAT'S AN EXAMPLE OF TESTING
HOW ARE WE ACTUALLY GOING TO
IMPLEMENT THIS SCREENING AND
TREATMENT ACROSS THESE DIVERSE
MEDICAL CENTERS.
AGAIN IMPORTANT TO THINK ABOUT
HOW SHOULD THESE IMPLEMENTATION
INTERVENTIONS BE TAILORED TO THE
SEX GENDER DIVERSITY OF THE
TARGET AUDIENCE.
I THINK THIS IS ALL SOMETHING WE
CAN THINK ABOUT IN OUR WORK.
IT'S ALSO IMPORTANT TO THINK
ABOUT AGAIN DESIGNING FOR
DISSEMINATION, HOW CAN MESSAGES
BE CRAFTED IN A WAY THAT
RESPONDS TO SEX AND GENDER
RELATED FACTORS WITHOUT
REPRODUCING OR EXPLOITING ANY
NEGATIVE STEREOTYPES EMBEDDED IN
INSTITUTIONALIZED GENDER.
SO THE LAST SECTION, JUST GOING
TO END ON KNOWLEDGE GAPS IN
FUTURE REACCEPT.
I RESEARCH.I KNOW THIS SOUNDS GT
MANY OF YOU ARE SAYING WHY DOES
IT MATTER, I'M NOT AN
IMPLEMENTATION SCIENCE.
BUT I DO THINK HOPEFULLY I'VE
CONVINCED YOU THAT THESE
PRINCIPLES AND CORE ELEMENTS OF
IMPLEMENTATION SCIENCE CAN BE
USEFUL BEYOND JUST
IMPLEMENTATION RESEARCH AND
HOPEFULLY ILLUSTRATE HOW
APPLYING THESE CORE ELEMENTS
EVEN AS EARLY AS THE
CONCEPTUALIZATION OF THE
TREATMENTS THEMSELVES AND EARLY
EFFICACY WORK ADD RIGOR AND
RELEVANCE TO THE RESEARCH, AND I
THINK IT'S EVEN MORE IMPORTANT
AS WE'VE TALKED ABOUT IN TERMS
OF SEX AND GENDER DIFFERENCES
THROUGHOUT THE OSA TREATMENT,
YOU KNOW, TREATMENT COURSE IN
TERMS OF THE BIOLOGY BUT ALSO
THE IMPLEMENTATION AND UP TAKE
OF EFFICACIOUS AND EMERGING
TREATMENTS.
FOR THOSE OF YOU INTERESTED,
THERE'S A FEW COMMENTARIES ON
SLEEP IMPL IMPLEMENTATION SCIEN.
I LIKE TO SHOW PEOPLE MY
NEW YORK ROOTS TO QUOTE YOGI
BERRA, IF YOU DON'T KNOW WHERE
YOU'RE GOING, YOU MIGHT WIND UP
SOMEPLACE ELSE.
AND TO THINK ABOUT WHERE YOU ARE
ON THIS SUBWAY MAP, AND REALLY
OUR GOAL I THINK AS A FIELD IS
TO IMPROVE SLEEP -- OBSTRUCTIVE
SLEEP APNEA HEALTH ON A
POPULATIONAL LEVEL ACROSS A
DIVERSE NUMBER OF PATIENTS, AND
IT'S IMPORTANT TO THINK ABOUT
THE END OF THE SUBWAY LINE EARLY
AND WHERE YOU ARE.
I JUST WAP TO GIVE A SHOUT OUT
EARLIER THIS YEAR,
DR. WILLIAMSON AND I STARTED A
SLEEP IMPLEMENTATION SCIENCE
LISTSERV, SO IF YOU'RE
INTERESTED, YOU CAN SCAN THIS QR
CODE OR EMAIL US, WE'LL BE HAPPY
TO JOIN YOU TO EXCHANGE
INFORMATION AND KNOWLEDGE AND
CREATE A COMMUNITY OF
RESEARCHERS INTERESTED IN SLEEP
DISSEMINATION IMPLEMENTATION
SCIENCE.
SO JUST TO WRAP UP SORT OF THE
MEAN OPPORTUNITIES I SEE IN THIS
FIELD IS HOW CAN SLEEP APNEA
RESEARCHERS EXPLICITLY CONSIDER
SEX AND GENDER ISSUES IN OSA
EVALUATION AND ADAPTATION
DELIVERING IMPLEMENTATION OF OSA
INTERVENTIONS IN REAL WORLD
SETTINGS.
HOW DO WE IDENTIFY PRACTICAL
STRATEGIES AND OPPORTUNITIES TO
USE IMPLEMENTATION SCIENCE FRAME
WORKS AND METHODS TO BROADEN OUR
PERSPECTIVES THAT INFORM
TREATMENT AND IMPLEMENTATION IN
REAL WORLD SETTINGS, AND HOW CAN
OSA PROTOCOLS AND PROGRAMS MORE
EXPLICITLY CONSIDERED SOCIAL
DETERMINANTS OF HEALTH AND
SEXUAL AND GENDER DISCRIMINATION
IN SCOPE AND COULD BE TEXT AND
WHAT ARE SOME OF THE UNINTENDED
CONSEQUENCES OF SOME OF THIS
WORK.
SO I REALLY LOOK FORWARD TO THE
DISCUSSION TODAY, A THA AND THAU
ALL FOR YOUR ATTENTION.
>> THANK YOU, DR. BERTISCH.
I WOULD LIKE TO INVITE ALL OUR
PANEL SPEAKERS, DISCUSSANTS, TO
JOIN THE DISCUSSION, AND DURING
THE SESSION WE LEARNED ABOUT THE
KEY ELEMENTS OF IMPLEMENTATION
SCIENCE AND WHAT CERTAIN TYPES
OF TRIALS WE CAN PLAN, VERY
INTERESTING, THOSE HYBRID
TRIALS, PERSONALLY I'M
INTERESTED IN THEM, AND LET ME
SEE.
ARE THERE ANY QUESTIONS FROM THE
PANEL?
I'M TRYING TO SEE IF THERE ARE
ANY HANDS UP THERE.
MAYBE I CAN ASK THE FIRST
QUESTION.
SO TO ALL THE PANELISTS, HAVING
HEARD THE DAY ONE TALKS AND
TODAY'S TALKS, WHAT DO YOU THINK
THAT OUR FIELD, THE OSA FIELD,
WHERE SHOULD WE START?
YOU SHOWED US ALL THESE
DIFFERENT OPPORTUNITIES, AND
DIFFERENT TYPES OF TRIALS.
WHAT WILL BE YOUR THOUGHTS, FOR
EXAMPLE, JONATHAN, WHAT DO YOU
THINK WE SHOULD BE DESIGNING AS
OUR NEXT STUDY?
>> SO FIRST OF ALL, I JUST WANT
TO SAY, I LEARNED SO MUCH FROM
THE WHOLE CONFERENCE AND
ESPECIALLY FROM THIS PANEL.
I THINK THERE'S A LOT WE CAN
LEARN FROM THE WORK THAT HAS
ALREADY BEEN DONE, SO I THINK IN
THE WAY THAT WE WOULD APPROACH
META-ANALYSIS OF EFFECTIVENESS
OUTCOMES, WE SHOULD BEGIN BY
LOOKING AT THE DIFFERENT
PRACTICE SETTINGS, THE DIFFERENT
PATIENT POPULATIONS, AND BEGIN
TO ASSIGN SOME SENSE OF HOW
THOSE VARY.
THE FOREST PLOT IS THE PREFERRED
WAY TO DO THAT.
I THINK THAT WILL GIVE US SOME
INSIGHT INTO WHICH ARE THE MORE
PROMISING SETTINGS AND
APPROACHES AND WHICH ARE THE
MORE PROMISING INTERVENTION
STRATEGIES THAT WE HEARD A LOT
ABOUT IN THE LAST TALK, AND THEN
I THINK THE NEXT STEP IS TO
BEGIN TO DESIGN TRIALS THAT
PROSPECTIVELY AND WITH
RANDOMIZATION IN USING
PATIENT-REPORTED OUTCOMES AS
WELL AS CLINICAL OUTCOMES IN
PRAGMATIC DESIGNS, HYBRID
EFFECTIVENESS, IMPLEMENTATION,
ALL OF THAT INTO THE NEXT ROUND
OF MULTISITE CLINICAL TRIALS.
>> THANK YOU.
ARE THERE ANY QUESTIONS? YES,
DR. STROLLO.
>> DR. TOBIN, YOUR TALK WAS
GRIET, AND TGREAT.
TRYING TO REACH OUT TO RURAL
COMMUNITIES IS A REAL CHALLENGE,
PARTICULARLY FOR ADULT CARE,
THERE ARE ACCESS ISSUES AND THEN
THERE ARE ALSO ISSUES IN TERMS
OF INITIATING CARE AND
INTEGRATING CARE.
FROM YOUR EXPERIENCE, IN OTHER
VENUES, DO YOU HAVE WORDS OF
WISDOM THAT KIND OF HELP?
>> SO THE MOST IMPORTANT THING
WHICH I THINK WE'VE HEARD A
COUPLE OF TIMES WHICH HAS DO
WITH ENGAGING THE WIDE RANGE OF
STAKEHOLDERS, AND SO OFTENTIMES,
WE CAN GET A GROUP OF
INVESTIGATOR, CLINICIANS AND
OTHERS TOGETHER AND COME UP WITH
SOME GREAT IDEAS.
BUT I THINK THAT'S NOT
SUFFICIENT AND PART OF IT, I
BELIEVE, IS REALLY UNDERSTANDING
WHAT THE BARRIERS OF DIFFERENT
POPULATIONS BOTH ON THE SERVICE
DELIVERY SIDE AND ON THE PATIENT
EXPERIENCE SIDE ARE, AND THEN
ENGAGE THOSE STAKEHOLDERS IN THE
DESIGN FOR DISSEMINATION
APPROACH SO THAT THEIR FEEDBACK
IS INCORPORATED EARLY ON.
JUST A BRIEF ANECDOTE, I ONCE
WORKED WITH A GROUP TO DESIGN A
NUTRITIONAL INTERVENTION FOR
HOMELESS INDIVIDUALS, WE WERE
VERY PROUD OF OURSELVES AND THEN
ONE OF THE PARTICIPANTS SAID,
WELL, I EAT OUT OF THE GARBAGE
PAIL, WHAT GOOD IS ANY OF THIS
INFORMATION TO ME?
AND JUST MADE ME FEEL RIDICULOUS
AT THAT POINT BECAUSE WE DIDN'T
ENGAGE THE END USERS IN A WAY
THAT WOULD HELP US DESIGN A
PROGRAM THAT WOULD ACTUALLY BE
HELPFUL, SO I THINK ENGAGEMENT
IS THE KEY.
>> DO YOU HAVE ANY OTHER
INSIGHTS IN TERMS OF LOW
SOCIOECONOMIC GROUPS IN URBAN
POPULATION VERSUS RURAL
POPULATIONS ON THE BASIS OF YOUR
WORK?
>> SO HOUSING IS A CHALLENGE IN
BOTH SETTINGS, IN HOUSING
DENSITY IN THE URBAN SETTING,
NOISE, I THINK ALL OF THESE
CONSIDERATIONS THAT DISRUPT
SLEEP ARE REALLY IMPORTANT, SO
THIS GOES BACK TO THE VIGNETTE I
JUST SHARED, AND I THINK WE
REALLY HAVE TO UNDERSTAND THE
HOME ENVIRONMENT IN ORDER TO BE
ABLE TO DESIGN INTERVENTIONS
THAT ARE LIKELY TO HAVE UPTAKE
ADHERENCE AND SUSTAINABILITY.
SO I THINK IT'S VERY DIFFERENT
DESIGNING FOR DISSEMINATION IN A
RURAL SETTING WHERE PEOPLE LIVE
IN LARGER SPACES THAN IN A MORE
CROWDED SETTING.
THAT'S NOT TO SAY THERE AREN'T
GOING TO BE CHALLENGES THERE,
BUT AGAIN, I THINK THE
ENVIRONMENTAL ASSESSMENT IS
GOING TO BE REALLY CRITICAL
TOITY SUCCESS.
>> THANK YOU.
I WOULD LIKE TO BRING UP THIS
INTERESTING QUESTION FROM
DR. OWENS THAT'S BEEN SOMEWHAT
ANSWERED IN THE CHAT, BUT IT
SEEMS LIKE MANY OF THE
IMPLEMENTATION TRIALS MENTIONED
TRY TO GET MORE PATIENTS IN THE
CLINIC, BUT THE CLINICS AND OUR
SLEEP STUDIES ARE BACKED UP,
POTENTIALLY WEARABLES IS A WAY
AROUND OR BRINGING, YOU KNOW,
THE CARE TO THE PRIMARY CARE AS
WE TALKED ABOUT EARLIER.
WHO WOULD LIKE TO TAKE THIS
QUESTION?
DR. HONAKER FROM A PEDIATRIC
PERSPECTIVE?
BECAUSE YOU'VE SHOWN SOME
EXCITING INITIATIVES.
>> YEAH, AND IN A LOT OF SENSE,
I'M LUCKY, IN UNANIMOUSLY, WE
HAVE 14 -- OR 16 PEDIATRIC BEDS,
AND SO WHEN I ENGAGED IN THIS
WORK TO INCREASE THE VOLUME OF
REFERRALS, WE WERE ABLE TO
MANAGE THAT.
THAT SAID, THAT IS CERTAINLY NOT
THE CASE EVERYWHERE, AND I'M
PERSONALLY VERY EXCITED ABOUT
THE IDEA OF SORT OF WEARABLES OR
CAMERAS DETECTING RISK WHERE WE
COULD AT LEAST HELP TO STRATIFY
WHICH KIDS ACTUALLY NEED PSG,
AND WHICH KIDS WOULD BENEFIT
FROM WATCHFUL WAITING AND WHICH
KIDS MAYBE SHOULD JUST GO
STRAIGHT TO SURGERY, AND I'M
REALLY EXCITED ABOUT WHAT THE
NEXT FIVE YEARS WILL BRING IN
TERMS OF DIAGNOSTIC AND
TREATMENT STRATEGIES.
BUT WE STILL NEED TO WORK ON
DOING A GOOD JOB OF FINDING THE
KIDS WHO ARE AT RISK AS WELL.
>> SUSHMITA, DO YOU HAVE A
QUESTION?
WE CANNOT HEAR YOU FOR SOME
REASON.
OR AT LEAST I CAN'T.
I GUESS MAYBE I CAN READ THE
QUESTION.
IT'S ABOUT RESOLVING THE TENSION
BETWEEN PRAGMATIC TRIALS AND
PERSONALIZED INDIVIDUALIZED
THERAPIES, HOW DO WE BALANCE
SORT OF THE REAL WORLD
APPLICABILITY OF PRECISION
MEDICINE?
I GUESS THIS IS A KEY QUESTION
INDEED.
>> I CAN JUMP IN.
>> THIS IS SOMETHING IN
LISTENING TO SPEAKERS TALK,
FIRST I UNDERSTAND THAT THERE
SEEMS TO BE THIS DICHOTOMY
BETWEEN WHAT'S PRAGMATIC AND
WHAT'S PERSONALIZED, BUT I DO
THINK TRYING TO GET LARGER
CLINICAL TRIALS FUNDED IN WHICH
WE COULD EXPLORE LIKE
HETEROGENEITY BECAUSE WITH THE
CLINICAL TRIAL METHODOLOGY, IT'S
VERY HARD TO GET SOMETHING
PERSONALIZED.
THAT WOULD BE LIKE AN N OF
1 TYPE OF STUDY, SO IN TRYING TO
IDENTIFY SOME OF THE PATIENT
PHENOTYPES OR ENDO TYPES THROUGH
THE LARGE STUDIES BY FIRST
EXPLORING HETEROGENEITY IN OUR
COMPARATIVE EFFECTIVENESS TRIAL
TO THEN KIND OF USE THAT AS A
TOOL TO THEN TAYLOR TREATMENT
RATHER THAN I FEEL LIKE WHAT
WE'RE DOING NOW IS TRYING TO GET
SO PERSONALIZED AND WE'RE NOT --
THE SCIENCE IN SOME WAYS SEEMS
TO ME TO BE GETTING STALLED
EARLY IN THAT RED PART OF THE
LOOP WITH SAYING OH, IT DOESN'T
WORK, WE NEED TO GET
PERSONALIZED, OR IT SEEMS LIKE
WE NEED TO BRING THINGS MORE
MAYBE INTO THE COMPARATIVE
EFFECTIVENESS SPACE AND DO
LARGER STUDIES COMPARING
TREATMENTS AND TRY TO MAKE THEM
BIG ENOUGH WHERE WE MAY BE ABLE
TO POWER FROM SOME OF THE
HETEROGENEITY, THEN GROUPS MAYBE
SEE SIGNALS AND THEN DO MORE
DEDICATED STUDIES, RATHER THAN
JUST TRYING TO PERFECT A CERTAIN
THOUGHT OR CERTAIN TREATMENT IN
THESE HIGHLY CONTROLLED
SETTINGS.
I THINK -- WHAT I THINK ABOUT
WITH MY CLINICIAN HAT ON, WHEN I
HAVE DISCUSSIONS WITH MY
PATIENTS ABOUT THESE ARE ALL THE
OPTIONS FOR SLEEP APNEA, YES, I
DON'T KNOW YET WHAT IS GOING TO
WORK FOR YOU.
WE DON'T HAVE A LOT OF
COMPARATIVE EFFECTIVENESS
STUDIES TO EVEN MAKE THOSE
SHARED DECISION-MAKING
INFORMATIVE TO BEGIN WITH AND
IT'S GOING TO TAKE US A LONG
TIME TO PER FOACT OUR
PERSONALIZED STRATEGIES SO I
DON'T SEE THEM AS NECESSARILY
DICHOTOMOUS.
I THINK WE SHOULD JUST MAYBE
REFRAME THE WAY WE'RE ACTUALLY
PRODUCING THE CLINICAL KNOWLEDGE
THROUGH THE TRIALS.
>> THANKS.
I DON'T KNOW IF YOU CAN HEAR ME
NOW.
YEAH?
>> YES, WE CAN.
>> OKAY, GOOD.
THANK YOU FOR THAT.
I GUESS I WAS THINKING ALSO IN
THE CONTEXT OF THE PRAGMATIC
TRIALS WHERE YOU TRY TO HAVE --
MAKE SURE IT'S GENERALIZABLE TO
YOUR POPULATION, YOUR INCLUSION
CRITERIA IS QUITE BROAD.
HERE WE ARE THINKING OF
SUBGROUPS, SO PUTTING THAT AS A
DESIGN, HOW DO WE DESIGN THOSE
TRIALS, I THINK WE'VE DISCUSSED
IN THE PAST THOSE ADAPTIVE
TRIALS AND KIND OF THESE MORE
NOVEL METHODS BUT ALSO SHOULD WE
BE STRATIFYING BASED ON
SUBGROUPS BUT ALSO KIND OF
KEEPING OUR GENERAL POPULATION
IN A WAY THAT'S FAIRLY BROAD AND
THAT WE CAN APPLY TO PRACTICE.
>> I WANTED TO FOLLOW UP ON THE
QUESTION FOR DR. HONAKER ABOUT
PEDIATRICS AND WEARABLES.
ONE OF OUR CHALLENGES IN THIS
FIELD THAT WAS TOUCHED ON
EARLIER TODAY WAS WE CAN'T
REALLY AGREE UPON WHAT'S SLEEP
APNEA IN CHILDREN, AND IN
POLYSONOGRAPHY IN LABS, WE
FREQUENTLY RELY ON
HYPOVENTILATION MEASURES SUCH AS
CO2 WHICH IS VERY DIFFICULT TO
IMPLEMENT WITH A WEARABLE IN AN
OUTPATIENT SETTING.
WE CAN USE A WEARABLE.
DO YOU THINK THAT -- IT SEEMS TO
ME THERE NEEDS TO BE MORE
RESEARCH TO UNDERSTAND THE PREA
SITION OF THIS MEASUREMENT,
PARTICULARLY IN A PEDIATRIC
POPULATION.
>> NO, I THINK THAT MAKES A LOT
OF SENSE EVEN WITHIN THE PSG,
THERE IS SOME CONTROVERSY ABOUT
WHAT METRICS ARE MOST IMPORTANT
AND YOU KNOW, AND ALSO A THINK
THIS WAS ALLUDED TO IN ONE OF
THE EARLIER TALKS, THAT PSG
POTENTIALLY IDENTIFIES SEVERITY
BUT IT DOESN'T TELL YOU WHERE
THE OBSTRUCTION IS ANATOMICALLY,
AND SO THERE ARE SOME
TECHNOLOGIES THAT SEEM REALLY
EXCITING THAT CANNOT JUST
IDENTIFY OSA BUT POTENTIALLY
SIDE OF OBSTRUCTION TO GUIDE
TREATMENT.
THAT SAID, VALIDATION, IT'S ALL
VERY COMPLEX.
I JUST THINK SOMETIMES PERFECT
CAN BE THE ENEMY OF GOOD, RIGHT,
AND WE DON'T HAVE GREAT IDEAL
TREATMENT PATHWAYS OR
PERSONALIZED APPROACHES BY ALL
THESE VARIABLES BUT I MEAN WE
KNOW THAT MOST KIDS RESPOND TO
TNA TO SOME DEGREE, AND SO I
THINK -- AND THE PSG WORKS WELL
ENOUGH, SO I THINK WHILE WE'RE
SORT OF TRYING TO GET A BETTER
HANDLE ON BEST PRACTICES FOR
DIAGNOSIS AND TREATMENT, WE
STILL NEED TO BE DOING WHAT WE
CAN WITH THE TREATMENTS THAT WE
HAVE.
>> THANK YOU.
THANK YOU TO ALL OUR SPEAKERS.
I'M SURE THERE ARE MORE
QUESTIONS, MORE DISCUSSION,
WHICH WE CAN DO DURING OUR
ROUNDTABLE.
AND I AM NOW ANNOUNCING OUR
BREAK.
BRITTANY, COULD YOU TELL ME WHEN
WE SHOULD BE BACK?
>> OF COURSE.
WE'LL ALL BE BACK AT 3:45.
>> 3:45.
THANK YOU SO MUCH.
>> YOU'RE WELCOME.
>> WELCOME BACK, EVERYONE.
SO FOR THE LAST SESSION WE HAVE
WHAT US A CALLED ROUNDTABLE AND
MYSELF, ANKIT AND ESRA WILL
MODERATE.
ANYONE WHO'S ACTIVE IN THE
DISCUSSION WE HAVE, PLEASE TURN
YOUR VIDEO ON SO WE CAN SEE YOUR
FACE AS WELL.
WE'LL DO OUR BEST TO MODERATE IN
THE CHAT AND ALSO IN THE Q & A.
IF THERE ARE QUESTIONS.
GENERALLY, WE'RE GOING TO FOCUS
IN THE FIRST 20 MINUTES ON
SESSIONS ONE AND TWO FROM
YESTERDAY, THEN I'LL TURN THE
MIC OVER TO ANKIT, HE'LL
MODERATE FOR ANOTHER 20 MINUTES
ON SESSIONS THREE AND FOUR AND
THEN WE'LL FINISH UP WITH SOME
OF THE DISCUSSION TODAY AND ESRA
WILL CLOSE OUT WITH THE LAST 20
MINUTES.
SO I THINK THAT THERE WERE MANY
DIFFERENT QUESTIONS AND
DISCUSSIONS THAT WE WILL GO
FORWARD WITH TODAY.
I'M GLAD WE HAVE A LOT MORE
TIME.
BUT I DID WANT TO SORT OF START
A LITTLE BIT, AGAIN, I THINK
MARISHKA HAD SORT OF ASKED WHAT
ARE WE BRINGING INTO THE CLINIC,
AND SORT OF WHAT'S THE MOST
INTERESTING.
SORRY, I THINK WE'RE ALL GETTING
DISTRACTED BY MOVING AROUND HERE
ON THE VIDEO, BUT YOU KNOW, I
THINK AS I'VE PRACTICED OVER THE
LAST 10 YEARS OR SO, THE THINGS
THAT HAVE REALLY BEEN
INTERESTING, I THINK SORT OF
LEARNING THAT MAYBE WE DON'T
NEED TO TREAT AN AHI OF 6.
I THINK WE HAVE NEW THERAPIES
LIKE HYPOGLOSSAL NERVE
STIMULATOR, I THINK THE WEIGHT
MANAGEMENT POTENTIAL IS REALLY
HUGE.
I WANTED TO START AND ASK
DR. STROLLO, CAN YOU REFLECT A
LITTLE BIT ON HOW YOUR CLINICAL
PRACTICE HAS CHANGED, AND OF THE
SCIENCE AND TALKS WE SAW FROM
DAY ONE, OSA ACROSS THE
LIFESPAN, WHAT ARE THE THINGS
THAT YOU'RE EXCITED ABOUT GOING
FORWARD?
>> I THINK THE GOAL OF THIS
WORKSHOP IS REALLY TO TRY TO
APPROACH PERSONALIZING CARE, AND
WHEN WE STARTED THIS FIELD,
EVERYTHING WAS CPAP.
AND NOW WE HAVE A LOT MORE TOOLS
IN THE TOOLBOX.
AND THERE ARE GOING TO BE
DIFFERENTIAL EFFECTS FOR PEOPLE
OF COLOR AND WOMEN, LIKE ONE OF
THE THINGS THAT WE'VE LEARNED
JUST WITH THE HYPOGLOSSAL NERVE
STIMULATION SPACE IS THAT WOMEN
ACTUALLY RESPOND BETTER TO UPPER
AIRWAY STIMULATION THAN MEN,
ALTHOUGH THEY ARE FREENGT
FREFREQUENTLYDENIED INSURANCE, T
AN UNCOMMON PROBLEM, THAT'S ALSO
FOR ALL MEDICAL DEVICES FOR A
DEPDEFIBRILLATOR, A WOMAN IS MOE
LIKELY TO BE DENIED BY
INSURANCE.
SO I THINK THAT'S A GAP WE WANT
TO ACKNOWLEDGE AND TRY TO FIX
AND THOSE DATA WERE PRETTY WELL
SORTED OUT WITH SOME OF THE
PAPERS WE HAD PUBLISHED
PREVIOUSLY.
I THINK YOUR OTHER POINT, BOB,
IN TERMS OF WHO DO YOU TREAT,
YOU KNOW, WE DIDN'T REALLY TALK
ABOUT IN THIS WORKSHOP, ARE
THERE PEOPLE THAT WE SHOULDN'T
TREAT BECAUSE ALITTLE A LITTLEF
SLEEP APNEA MIGHT BE GOOD FOR
YOU AND MAYBE THIS NOTION OF
PREISCHEMIC CONDITION.
SUSAN WAS INVOLVED IN A PAPER
WITH ALI LOOKING AT RELATIVELY
LOW HYPOXIC BURDEN, ALTHOUGH IT
WASN'T THAT LOW, VERSUS HIGH
HYPOXIC BURDEN IN THE ISAAC
TRIAL AND PEOPLE EXPOSED TO CPAP
HAD WORSE CARDIOVASCULAR
OUTCOMES THAN PEOPLE WITH HIGH
HYPOXIC BURDEN, WHICH IS AN
INTERESTING OBSERVATION.
SO I THINK WE HAVE TO BE CAREFUL
IN WHO WE TREAT.
WE DON'T REALLY UNDERSTAND WHAT
THE THRESHOLD IS.
AND I THINK NARESH VERY NICE
LEHIGH LIGHTED ON THE FIRST DAY
THAT WE HAVE SO MANY DIFFERENT
METRICS THAT WE'RE REALLY --
THERE'S A LOT OF UNCERTAINTY,
EVEN IN THE ADULT SPACE AS
OPPOSED TO THE PEDIATRIC SPACE
WHICH IS EVEN MORE CHALLENGING.
SO THOSE WOULD BE MY THOUGHTS,
BUT I THINK PERSONALIZED CARE IS
GOING TO REQUIRE A VARIETY OF
DIFFERENT METRICS AND MAYBE LIKE
WHAT ALLEN SAID, POLYGENETIC
RISKS, DIEGO HAS BEEN WORKING IN
THAT AREA, WILL HELP GUIDE US.
I THINK THE LAST THING I WILL
SAY IN TERMS OF WHAT I THOUGHT
WAS REALLY EXCITING WAS THE
WHOLE NOTION OF SIMULATION, AND
BEING ABLE TO SIMULATE A PATIENT
BASED ON A DEEP DIVE INTO THE
DATA TO TRY TO TARGET THE
APPROPRIATE TREATMENT UP FRONT,
BECAUSE RIGHT NOW WE USUALLY
APPROACH PATIENTS, GIVE THEM
CPAP, THAT DOESN'T WORK, WE'LL
GO TO OTHER OPTIONS THAT ARE
MORE AGGRESSIVE.
>> THANKS.
I'VE ALWAYS THOUGHT OUR SLEEP
STUDY RIGHT NOW HAS ALL THESE
METRICS INCLUDING AHI AND A
BILLION OTHER STATISTICS.
WE COULD TALK ABOUT HOW MAYBE WE
AS A FIELD COULD ACTUALLY
STANDARDIZE OUR SLEEP REPORTS SO
WE DON'T LOOK LIKE REALLY SLOW
WHEN WE'RE TRYING TO READ AN
OUTSIDE REPORT, BUT THE BEST
SLEEP STUDY WOULD BE HERE'S WHY
YOU HAVE SLEEP APNEA, HERE'S THE
TREATMENTS THAT MIGHT WORK FOR
YOU, AND HERE'S HOW YOU'D FEEL.
YOU'D FEEL LIKE YOU GOT TWO MORE
HOURS OF SLEEP, OR YOUR BLOOD
PRESSURE WOULD GET BETTER OR
WHATEVER.
LET ME ASK NAJIB, WHAT DO YOU
THINK HAVE BEEN THE BIG
PRACTICES OVER YOUR CAREER IN
TERMS OF HOW WE TREAT SLEEP
APNEA, ONE WE SAW WITH SOME OF
THESE OUTCOMES, ARE THERE THINGS
YOU WERE EXCITED ABOUT FROM THE
FIRST COUPLE SESSIONS?
>> JUST FOR THE SAKE -- I WORK
IN CANADA SEW WE ACTUALLY DON'T
HAVE HYPOGLOSSAL NERVE
STIMULATION HERE.
I DON'T KNOW IF MY CLINICAL
PRACTICE HAS REALLY CHANGED THAT
MUCH IN THE LAST 10 YEARS.
I THINK 10, 15 YEARS AGO, I WAS
GETTING AN AHI ON PEOPLE AND
PUTTING PEOPLE ON CPAP AND
TELLING PEOPLE TO LOSE WEIGHT IF
THEY CAN, AND I THINK I'M KIND
OF DOING THE SAME THING NOW.
HONESTLY QUITE A FEW YEARS AGO,
A LITTLE BIT DOWN ON THE FIELD
TO BE HONEST BECAUSE I JUST FELT
LIKE WE'RE DOING THE SAME THINGS
OVER AND OVER.
I THINK IN THE LAST COUPLE OF
YEARS I'M MORE HOPEFUL BECAUSE
OF A LOT OF THIS WORK THAT'S
BEING DONE.
I DON'T KNOW IF A LOT OF THE
STUFF YOU PRESENTED HERE IS
NECESSARILY READY FOR PRIME TIME
OR THOSE KINDS OF THINGS, BUT IT
LOOKS PRETTY HOPEFUL AND LOOKS
PRETTY EXCITING AS WELL.
LIKE IF I COULD THINK OF THINGS
THAT I THINK PEOPLE ARE REALLY
EXCITED ABOUT IN GENERAL, EVEN
PEOPLE WHO AREN'T IN THE SLEEP
FIELD, JUST GENERAL RESPIRATORY
AS WELL, I THINK THAT THINGS
THAT WE ARE HOPEFUL ABOUT IS
PROBABLY THE PHARMACEUTICAL
APPROACHES TO SLEEP APNEA AND I
THINK THAT THAT LENDS ITSELF TO
SORT OF THE PHYSIOLOGIC
ENDOTYPING AND MAKES PHYSIOLOGY
MO IMPORTANT AS WELL.
I THINK THE WHOLE THING WITH THE
LINKS BETWEEN OBESITY AND HAVING
TREATMENT TO TREAT THE OBESITY
AND TREAT THE SLEEP APNEA I
THINK IT'S GOING TO CHANGE THE
WAY WE PROBABLY MANAGE THESE
PATIENTS AND THE LINKS BETWEEN
WHETHER WE START PRESCRIBING
SOME OF THESE MEDICATIONS AND
MORE SYSTEMATICALLY AS WELL.
I THINK ALL THESE NEWER METRICS
I THINK IS VERY EXCITING AS
WELL, BUT I WOULD GIVE THE
CAVEAT THAT I THINK IT WAS ALLEN
PACK OR MAYBE IT WAS ANKIT WHO
SAID THEY ARE KIND OF
PROLIFERATING VERY QUICKLY.
THE PROBLEM YOU GET INTO IS IT'S
VERY EASY TO GENERATE A LOT OF
THESE METRICS AND THE QUESTION
IS WHAT DO THEY MEAN
BIOLOGICALLY, AND YOU KNOW, WHAT
EXTRA INFORMATION DO THEY OFFER.
SO IF THEY MAKE YOUR PREDICTION
FROM 89 TO 89.5, I'M JUST NOT
SURE IF IT'S REALLY WORTH IT SO
I THINK WE KIND OF HAVE TO
FIGURE OUT WHICH OF THESE
METRICS ARE ACTUALLY GIVING NEW
INFORMATION VERSUS JUST SORT OF
REDUNDANT INFORMATION, DO THESE
EXTRA DIMENSIONALITIES MAKE THAT
MUCH SENSE OR ARE THEY MEASURING
OTHER ASPECTS OF THE DISEASE AS
WELL.
BUT YEAH, I THINK IT'S AN
EXCITING TIME BECAUSE I THINK
JUST LIKE WHAT YOU SAID, BOB, I
THINK IT WOULD BE NICE TO BE
ABLE TO GET THIS SLEEP STUDY OR
MAYBE INCORPORATE CLINICAL
STUFF, BAY OWE CHEMICAL STUFF AS
WELL, AND BE ABLE TO TELL THE
PERSON AND SAY LIKE YOU SAID
WELL THIS IS THE LOCATION OF
WHERE YOUR SLEEP APNEA IS, THIS
MIGHT BE WHY YOU MIGHT HAVE IT,
THESE ARE THE THERAPIES THAT
WOULD WORK BEST IN YOU, AND THE
PROBABILITY THAT THEY WOULD
WORK.
THESE ARE HOW YOU WOULD FEEL OR
IN TERMS OF QUALITY OF LIFE, YOU
KNOW, IMPROVEMENTS OR SLEEPINESS
IMPROVEMENTS, IF YOU GET
TREATMENT THESE ARE THINGS YOU
ARE AT RISK OF LONG TERM,
WHETHER IT BE DEMENTIA, HEART
DISEASE, HYPERTENSION OR THOSE
THINGS AS WELL, I THINK IT WOULD
BE ABLE TO BE NICE TO GIVE
PEOPLE A NUANCE OF WHAT'S GOING
ON.
SO I THINK WE ARE HEADED IN THAT
DIRECTION.
I THINK ONE OF THE ISSUES IS I
DON'T KNOW IF WE HAVE ENOUGH
DATA TO ACTUALLY DO A LOT OF
THINGS THAT WE WANT TO DO, SO
ONCE YOU'RE LOOKING AT THESE
HIGH DIMENSIONALITY OR MULTIPLE
DIMENSIONS, I THINK DOING A
COHORT OF A THOUSAND OR 5,000
PEOPLE, I JUST DON'T KNOW IF
THAT'S ENOUGH THERE, SO I THINK
THAT ANYTHING WE CAN DO TO KIND
OF PULL DATASETS TOGETHER TO
KIND OF REALLY GET THAT MUCH
DATA SO WE CAN APLAY THESE A.I.
TECHNIQUES OR THESE THINGS
WITHOUT REALLY OVERFITTING DATA
AND JUST COMING UP WITH STUFF
WHICH ENDS UP NOT BEING TRUE, I
THINK ARE IMPORTANT.
BUT OBVIOUSLY THESE THINGS NEED
TO BE TESTED BEFORE WE PUT THEM
INTO CLINICAL PRACTICE AS WELL.
SO THOSE ARE JUST MY MAJOR
THOUGHT AT THIS POINT.
>> SO I FEEL LIKE A LOT OF WHAT
YOU TOUCHED ON, GREAT PERSON TO
TALK ABOUT THAT IS GOING TO BE
DIEGO, SO I'M SORT OF PUTTING
YOU ON DECK HERE FOR A SECOND.
BUT LIKE YOU SAID, I THINK DELTA
HEART RATE, I THINK IS A
GREAT -- IT'S A REALLY
INTERESTING METRIC.
I ALWAYS WONDER, IS THAT A SLEEP
APNEA-SPECIFIC THING?
IS THAT THE IMPACT OF OSA OR IS
THAT LIKE A STRESS TEST EVERY
TIME YOU HAVE AN AROUSAL FROM
SLEEP?
INSTEAD OF HAVING A RESPIRATORY
AROUSAL, SOMEBODY COULD AROUSE
YOU FROM SLEEP AND YOU WOULD SEE
SOME OF THE SAME INFORMATION, SO
IS THAT SLEEP APNEA SPECIFIC, IS
THAT JUST A METRIC OF THE
CARDIOVASCULAR SYSTEM?
SO DIEGO, MY QUESTIONS TO YOU
ARE, YOU KNOW, DO WE HAVE ENOUGH
DATA, AND THEN HOW EASY WOULD IT
BE TO KIND OF GENERATE SOME OF
YOUR WORK, PUTTING PEOPLE IN
DIFFERENT CLUSTERS, HOW COULD WE
GET THAT INTO THE CLINIC?
WHAT WOULD IT TAKE TO DO THAT?
>> I THINK THAT'S A GREAT POINT
AND I THINK THAT CAN REALLY --
IF WE PUT TOGETHER ALL THE
DIFFERENT CLINICAL DATASETS THAT
MANY OF THE SLEEP LABS AROUND
THE WORLD ARE WORKING ON, AND WE
HAVE TO DO THIS LIKE REALLY
WELL, RIGHT, I'M ASSUMING THAT
THERE'S A LOT OF HETEROGENEITY
ON HOW DATA IS COLLECTED, WHAT
INFORMATION IS AVAILABLE.
I CAN JUST TALK ABOUT TALK ABOUT
SOME OF THE WORK DONE AT THE
SLEEP APNEA CONSORTIUM WHICH WAS
VERY CHALLENGING TO JUST LIKE
PULL THOSE SLEEP STUDIES
TOGETHER, WHEN YOU'RE PULLING,
YOU KNOW, SIGNALS WITH DIFFERENT
NAMES AND DIFFERENT LANGUAGES,
CHANNELS, DIFFERENT WAYS LIKE
SAMPLING RATES AND THINGS LIKE
THAT, SO I THINK THAT A LOT OF
WHAT WE LEARNED FROM LIKE THE
NATIONAL -- RESOURCE WHICH WAS A
FANTASTIC EFFORT TO TRY TO
AGGREGATE SOME OF THOSE MORE
LIKE RESEARCH LEVEL SORT OF
STUDIES, WE NEED TO LEARN FROM
THAT EXPERIENCE AND THEN NOT
TAKE ON THE NEXT CHALLENGE OF
HOW WE CAN DO THESE ACROSS VERY
HETEROGENEOUS CLINICAL
PRACTICES.
NOW THIS IS ONLY ONE POINT OF
DATA THAT COULD MATTER TO US BUT
IT A REALLY FUNDAMENTAL ONE
BECAUSE IT CAN HELP US ADDRESS
THOSE QUESTIONS LIKE WE HAVE
NOW -- THE GREAT HYPOTHESIS
ABOUT THE IMPACT OF THOSE TRAITS
OR THOSE DIFFERENT NOVEL MARKERS
FROM COMMUNITY-BASED STUDIES,
EVEN FROM SOME CLINICAL
POPULATIONS AS WELL.
BUT WE DON'T REALLY HAVE A LOT
OF INFORMATION ABOUT HOW THEY
WILL IMPACT THERAPY.
NOW, IF WE THINK ABOUT
RETROSPECTIVELY, WE HAVE
THOUSANDS, MILLIONS OF PATIENTS
THAT HAVE BEEN TREATED FOR SLEEP
APNEA.
SO IF WE PUT REALLY A GREAT
EFFORT OF TRYING TO CREATE THOSE
CLINICAL DATA REPOSITORIES IN
COLLABORATION, ENSURING THAT
STUDIES CAN BE HARMONIZED ACROSS
THE BOARD, THEN WE CAN START
SOME OF THE METHODS THAT ANKIT
BROUGHT YESTERDAY LIKE DIGITAL
TWINS, WE MIGHT BE ABLE TO FIND
SUFFICIENT PEOPLE WHERE WE CAN
TASK -- LIKE -- BETWEEN THAT DID
RECEIVE THE THERAPY, INDIGENOUS
WOMEN DIDN'T, YOU KNOW, ACROSS
MILLIONS OF PATIENTS AROUND THE
WORLD, AND START INFERRING THOSE
CAUSAL EFFECTS.
SO TO TIE THIS WITH SOME OF THE
DISCUSSION WE HAD LAST, CAN WE
LEARN FROM THE DATA THAT'S BEEN
COLLECTED RETROSPECTIVELY TO
THEN INFORM WHAT'S GOING TO BE
THE NEXT PERSPECTIVE PRAGMATIC
TRIAL YOU WANT TO DO.
AND I THINK THERE'S A LOT OF
ROOM OPPORTUNITY ON TRYING TO
ACCOMPLISH THIS, AND I THINK THE
FIRST STEP IS REALLY JOINING AS
A TEAM TO START HARMONIZING,
ORGANIZING THIS DATA AND JUST
PUTTING THAT TOGETHER SO WE CAN
START ASKING THOSE QUESTIONS
PRIOR TO WHAT WE DO TRIALS.
>> I LOVE THE IDEA OF THE
INSILICO, YOU KNOW, VIRTUAL
THERAPY AND SEE WHAT THAT LOOKS
LIKE FOR A PATIENT AND COME
BACK.
SO I WANT TO HAVE MONICA, IF
YOU'RE ABLE TO COME ON TO VIDEO
AND SORT OF ASK YOUR QUESTION,
BECAUSE I USE PERSONALIZED
MEDICINE AND PRECISION
INTERCHANGEABLY AND MAYBE YOU
COULD ASK YOUR QUESTION AND THEN
SUSAN I'D LIKE TO PUT YOU ON
DECK AND TALK FOR JUST A MINUTE
ABOUT THE CHALLENGES OF GETTING
THE NSRR UP AND RUNNING, YOU
KNOW, WHAT DID THAT TAKE AND
WHAT WOULD IT TAKE TO EXPAND
THAT BY 10 OR 100?
BUT MONICA, ARE YOU ABLE TO ASK
YOUR QUESTION ON VIDEO?
ITHERE YOU ARE, THANK YOU.
>> THANKS, BOB.
NO, I HEARD BOTH THE TERMS
MENTIONED TODAY, AND IN SOME
INSTANCES, THE SPEAKERS WERE
USING THEM INTERCHANGEABLY, SO I
JUST WANT TO BE CLEAR IN WHAT
CONTEXT ARE WE USING
PERSONALIZED MEDICINE VERSUS
PRECISION MEDICINE.
IN MY MIND THEY ARE TWO VERY
DIFFERENT THINGS.
I THINK THE FIELD WANTS TO
EVENTUALLY GET TO PRECISION
MEDICINE, A VERY TARGETED TYPE
OF TREATMENT SO THE RIGHT
TREATMENT FOR THE RIGHT PATIENT
AT THE RIGHT TIME.
WE'RE NOT THERE YET, BUT I THINK
THAT'S WHERE WE WANT TO BE.
THE DEFINITION OF PRECISION
MEDICINE HAS BEEN EVOLVING IN MY
SENSE FOR THE PAST FEW YEARS.
ARE WE THERE YET?
DO WE EXACTLY KNOW WHAT THE
DEFINITION IS?
PERSONALIZED MEDICINE DEFINITION
HAS BEEN AROUND FOR A WHILE, BUT
I THINK I JUST WANTED TO HEAR
YOUR THOUGHT ON THAT AND WHERE
DOES THIS FIELD WANT TO BE
EVENTUALLY?
>> I WILL DEFINITELY LEAVE THAT
OPEN FOR ANOTHER PANELIST,
BECAUSE I THINK I OFTEN USE
PERSONALIZED, PRECISION, AND
OTHER TERMS INTERCHANGEABLY.
>> -- USE PRECISION MEDICINE
QUITE A BIT AND THEY RELY ANNOT
ON GENETICS, BUT I THINK IT
NEEDS TO BE MORE THAN THAT.
I WOULD LOVE TO HEAR YOUR
THOUGHTS ON THAT.
I THINK THAT'S A GREAT WAY FOR
US TO AT LEAST DEFINE WHERE WE
WANT TO BE AS A SLEEP APNEA
FIELD.
>> SO SUSHMITA HAS HER HAND UP,
MAYBE SHE'S WILLING TO ANSWER
THAT.
>> VERY INTERESTING QUESTION.
I THINK I'M GUILTY OF THE SAME,
OF USING IT INTERCHANGEABLY.
BUT I THINK ONE OF THE THINGS
THAT WE HAVEN'T TALKED A LOT
ABOUT TODAY THAT MIGHT BE MORE
RELEVANT TO PERSONALIZED
MEDICINE IS PATIENT PREFERENCES
AND PATIENT CHOICE.
SO REALLY PATIENT LEVEL OF
CHARACTERISTICS ON WHAT
TREATMENT THEY PREFER OR LIKE OR
DISLIKE, MAYBE WITH RESPECT TO
THEIR UNIQUE ENVIRONMENT OR
OTHER SORT OF SOCIAL SITUATION.
SO I WONDER IF THAT'S SOMETHING
THAT DOESN'T REALLY GET
INCORPORATED INTO PRECISION
MEDICINE BECAUSE I SEE THAT MORE
AS AN OMICS-TYPE MOLECULAR --
BUT I DON'T KNOW.
IT'S JUST A THOUGHT.
>> IRINA, YOU HAVE YOUR HAND UP?
>> SO I JUST WANTED TO PUT A
COUPLE OF THOUGHTS AS A
STATISTICIAN AND QUANTITATIVE
PERSON.
AT THE UNIVERSITY OF MICHIGAN WE
HAVE A PRECISION MEDICINE CENTER
AND EVEN THOUGH THAT INITIATIVE
STARTED WITH COLLECTING GENETICS
DATA, THE TERM ITSELF AS
PRECISION MEDICINE WENT FURTHER
BEYOND JUST THE GENETICS AND
OTHER CHARACTERISTICS, BUT I
REALLY WANT TO AGREE WITH
SUSHMITA'S POINT THAT I FEEL
LIKE WHEN WE TALK ABOUT
PERSONALIZED, WE HAVE TO TAKE
INTO ACCOUNT THE PATIENT'S
PREFERENCES IN TERMS OF THE
OUTCOMES THAT WOULD BE IMPORTANT
FOR THEM AND WHAT ARE THINGS
THAT THEY WILL BE WILLING AND
NOT WILLING TO DO AS A
TREATMENT.
WHEREAS PRECISION WOULD BE MORE
TALKING ABOUT THE
CHARACTERISTICS OF A HUB IN
TERMS OF THE POTENTIAL EFFICACY
OF THE TREATMENT.
>> I WANT TO HOLD ON SOME OF THE
QUESTIONS.
SUSAN ARE YOU ABLE TO GIVE SORT
OF A ONE MINUTE ON HOW MUCH
BLOOD, SWEAT AND TEARS DID IT
TAKE TO GET NSRR GOING?
AND MAYBE THAT WOULD BE REALLY
HELPFUL.
>> THAT'S A REALLY GOOD
QUESTION.
I DON'T THINK IT WAS A PROBLEM
GETTING GOING.
IT'S ONGOING EFFORT, AP AGAIN, I
NEED TO ACKNOWLEDGE NHLBI HAS
BEEN INCREDIBLY SUPPORTIVE
BEGINNING WITH MICHAEL AND NOW
WITH MARISHKA BROWN IN REALLY
GIVING US THE FUNDING TO
ACTUALLY WORK WITH THE
COMMUNITY.
I PUT THE REFERENCE IN THE CHAT,
AND THE BIGGEST PROBLEMS ARE
TWOFOLD.
ONE IS REALLY JUST THE
WILLINGNESS OF PEOPLE TO SHARE
THEIR DATA, AND I WANT TO -- YOU
KNOW, AND I THINK EVERYONE NOW
WHO GETS NIH FUNDING TO DO SLEEP
RESEARCH IN THE U.S. HAS A
MANDATE TO SHARE THAT DATA, AND
I DO HOPE THAT EVERYONE TAKES
THAT SERIOUSLY AND I KNOW THAT
NHLBI OR NATIONAL CENTER FOR
SLEEP DISORDERS RESEARCH IS A
HAS ENCOURAGED SLEEP RESEARCHERS
TO CONTACT NSR AND WE WILL WORK
WITH YOU.
SO JUST WANTED TO SAY THAT THE
FIRST BARRIER -- THEN THERE ARE
REGULATORY ISSUES BUT I THINK
GOING FORWARD, IF YOU COLLECT
YOUR DATA USING SORT OF THE
COMMON PROTOCOL, ET, YOU CAN --
LANGUAGE FOR DATA SHARE, THERE'S
NO REASON TO HIDE BEHIND THAT.
WHERE I THINK THE BIGGEST
PROBLEM DIEGO IS REFERRING TO IS
THE AMOUNT OF EFFORT MY STAFF
SPENDS IN CLEANING DATA WE GET
FROM SAIR JUST SOURCES BECAUSE
OF ALL THE INCONSIST 1 TENNESSES
AND LACK OF HARMONIZATION WITH
DEVICES, PEOPLE LABEL CHANNELS,
THE FILTERS THAT GET PUT IN, AND
I VA TO SAY WE'RE WORKING VERY
HARD AND MY COLLEAGUE SHAWN
PURCELL HAS CREATED SOME REALLY
NICE OPEN SOURCE TOOLS, SO A LOT
OF THAT WORK OF SHARING DATA,
WHICH YOU KNOW, REALLY THE --
WHICH SLOWS US DOWN IS DOING
THAT SECONDARY HARM NIGH STATION
IN CLEANING UP, AND WHAT WE ARE
NOW DOING IS CREATING MSR
VERSIONS OF BOTH THE ROTH
SIGNAL, THE METADATA AND THE
SUMMARY VARIABLE, BUT IF THAT
COULD BE DONE BY EACH OF YOU UP
FRONT, IT TAKES OFF A HUGE
AMOUNT OF WORK.
AND WE ARE WORKING AT
PUBLICIZING IT AND I KNOW I
SPOKE TO -- DIEGO AND I HAVE
TALKED ABOUT EVEN ENGAGING THE
COMMUNITY MORE INTERACTIVELY, SO
IT'S NOT JUST THE MSR GROUP
THAT'S PUTTING THE STANDARDS OUT
THERE, AND MSR IS '04 FOR
HOSTING WEBINARS OVER THE NEXT
FEW MONTHS TO, AGAIN, CONTINUE
TO ENGAGE THE COMMUNITY SO WE
COULD DO THIS TOGETHER.
AND I ALSO WANTED TO MENTION,
SOME OF THESE ISSUES ARE GOING
TO BE DISCUSSED ON WEDNESDAY
WITH A BIO -- CATALYST WEBINAR
WHERE WE'LL TALK ABOUT SOME OF
THE THINGS.
SO IF THE COMMUNITY WORK
TOGETHER, I WOULD SAY THE LIFT
IS NOT HIGH, AND THERE IS NO
LIMIT TO SHARING OF DATA.
>> JUST SO -- AN EXTRA TO WHAT
SUSAN JUST SAID WHICH IS AN
EFFORT THAT THE SLEEP -- THIS
TASK FORCE, THE RESEARCH
NETWORK, SO MANY ON THIS CALL
ARE ACTUALLY MEMBERS, INCLUDING
SUSAN AND ARI WILLIAMSON.
WE'RE TRYING TO COLLECT
INFORMATION ABOUT HOW DIFFERENT
CLINICAL SITES AND SLEEP ARE
REALLY COLLECTING YOUR DATA AND
WHAT OTHER INFORMATION IS
AVAILABLE THAT COULD BE LINKED,
FROM THE EHR OR THERAPY DATA.
SO WE LEARNED A LOT ABOUT OVER
25 SITES, BUT IF ANYONE IS
INTERESTED IN SHARING THE
INFORMATION ABOUT YOUR OWN SITE
AND YOUR OWN CENTER TO HELP US
DESIGN HOW WE CAN PROPOSE AN
APPROACH THAT CAN FACILITATE
THIS WORK FOR EVERYBODY, I THINK
WE ARE GETTING CLOSER TO OUR
ULTIMATE GOAL HERE, WHICH IS
FACILITATE THE NEXT STEP --
THANKS, SUSAN.
>> THE ONLY THING I JUST WANT TO
ADD, AGAIN FOR RESEARCHERS,
SOUNDS LIKE YOU'RE STARTING YOUR
STUDIES.
I WOULD BEGIN WITH DESANING YOUR
DATA COLLECTION PROACTIVELY, SO
THERE'S NOT A LOT OF CLEAN-UP
THAT GET DONE, AND IF YOU LIKE
TO DEPOSIT AN NSR, MY STAFF WILL
HELP WORK WITH YOU TO CREATE
STANDARDIZED METADATA AND SPHAL
LABELS AND TO FORTH.
SO THANKS.
>> I THINK WHEN YOU WRITE YOUR
DATA SHARING PG PLAN FOR AN NIH
GRANT, I THINK YOU ASSUME YOU
HAVE THE DATA AND THEN YOU'LL
SHARE IT LATER, BUT I LOVE YOU
HAVE SOME SUGGESTED FORMATS FOR
BEFORE YOU COLLECT YOUR DATA.
NAJIB, I SEE YOUR HAND UP, ONE
OF THE COMMENTS IN THE Q & A
FROM EMMA COOKSEY IS ABOUT
PROLIFERATION OF THESE DIFFERENT
OUTCOMES.
NOT ONLY IS IT CONFUSING FOR US,
BUT IT'S CONFUSING FOR PATIENTS,
AND SHE'S ASKING IS THERE ONE
METRIC THAT CAN BE -- I WANT TO
START TALKING ABOUT IS THERE ONE
METRIC THAT RULES THEM ALL OR DO
WE ACTUALLY NEED ALL THESE
DIFFERENT METRICS BECAUSE SLEEP
IS SO IMPORTANT?
>> WHEN YOU SAY OUTCOMES, I
ASSUME YOU MEAN MORE LIKE
PHYSIOLOGIC METRICS OR SOMETHING
FROM PSG OR THOSE THINGS?
I'M NOT SURE --
>> YEAH, AHI 3% --
>> I WAS THINKING MORE LIKE
DYING NOSTIVE WITH DECIDE ON A
TREATMENT OPTION AND THE
CLINICIAN IS GIVING THEM OPTIONS
BUT THEY'RE PRESENTING IT BY
SAYING CPAP, WE'RE GOING TO AIM
TO REDUCE YOUR AHI UNDER 5 AND
THE SAME WITH ORAL APPLIANCES,
BUT NOW IT SEEMS LIKE WHEN WE'RE
TALKING ABOUT ESPECIALLY SOME OF
THE NEW MEDICATIONS, A LOT OF
THE TALK SEEMS TO BE AROUND
HYPOXIC BURDEN, AND SO FOR A
PATIENTS IT CAN BE REALLY
CHALLENGING.
SO I'M NOT SURE IF IT'S ONE
METRIC OR IF WE NEAT MULTIPLE TO
DECIDE ON THE RIGHT TREATMENT
OPTION.
>> I DON'T HAVE AN ANSWER FOR
YOU, OTHER PEOPLE MAY.
I THINK WE'VE SORT OF HUNG OUR
HAT ON AHI FOR MANY, MANY YEARS.
I'M NOT TOO SURE WHY.
YOU CAN ARGUE AND SAY OH, IT'S
JUST THIS FREQUENCY BASED
METRIC, IS IT 3%, BUT THAT'S
WHAT WE'VE HUNG OUR HAT ON AND
WHAT WE HAVE THE MOST EXPERIENCE
WITH, SO I GUESS AT THIS POINT
FROM A CLINICAL STANDPOINT, I
GUESS THAT ES WHAT I THAT'S WHAL
PATIENTS CLINICALLY.
THE HOPE DOWN THE ROAD IS THAT
HOPEFULLY -- THE POINT I WOULD
MAKE AS WELL, IT SEEMS HIGHLY
UNLIKELY THAT ONE METRIC IS
GOING TO PREDICT ALL THE
OUTCOMES ASSOCIATED WITH SLEEP
APNEA.
SO I THINK THAT GIVEN AS BOP
SAID HOW MUCH SLEEP AFFECTS KIND
OF EVERYTHING, WHETHER IT BE
MOOD, CRASH RISK, BLOOD PRESSURE
OR THOSE KIND OF THINGS, IT
SEEMS HIGHLY UNLIKELY THAT ONE
METRIC IS GOING TO RULE
EVERYTHING LIKE "LORD OF THE
RINGS" OR SOMETHING SO IT'S VERY
LIKELY THAT CERTAIN METRICS WILL
BE BETTER FOR PREDICTING
ALZHEIMER'S DISEASE SO IT
WOULDN'T -- IT MIGHT BE -- IT'S
CERTAINLY POSSIBLE THAT SOME OF
THE BIOLOGICAL MARKERS YOU GET
SOME BLOOD, IT WOULDN'T SURPRISE
ME IF THOSE WOULD BE MORE
EFFECTIVE IN PREDICTING CARD JOE
VASCULAR DISEASE OR THOSE KINDS
OF THINGS AS WELL.
SO YA I DON'T KNOW.
MY GUT FEELING IS THAT 10 YEARS
FROM NOW, THIS THING ABOUT OHI
AND HI THIS -- WHY ARE WITH
DOING THAT?
I THINK YOU WANT TO GIVE -- TO
THIS ENTIRE PANEL SAYING THESE
ARE THE DIFFERENT DIMENSIONS AND
THE DANGERS AS STUFF LAKE THAT
AS WELL, EVEN CANCER RISK, I
THINK IT'S HIGHLY UNLIKELY THAT
THE SAME THINGS THAT PREDICT
SOMEONE GETTING STROKE IS GOING
TO BE THE SAME AS SOMEONE
GETTING LUNG CANCER OR BREAST
CANCER, MELANOMA OR THOSE THINGS
AS WELL, SO THAT'S KIND OF MY
FEELING.
THE ONLY POINT I WANTED TO MAKE,
I'M NOT AN EXPERT OF THE
PHYSICIAN VERSUS PERSONALIZED
CARE.
WHEN I THINK OF PR PRECISION I
USUALLY THINK OF HIGH-THROUGHPUT
TYPE OF DATA, LIKE WHETHER IT BE
OWE MINGOMICS OR GENETICS, I WOT
HIGH-THROUGHPUT PHYSIOLOGY IN
THAT CATEGORY AS WELL, LET'S SAY
IF YOU HAVE CIRCUMFERENTIAL
NARROWING YOU DON'T DO WELL WITH
HYPO -- THAT SEEMS LIKE MORE OF
A PERSONALIZED KIND OF APPROACH
THAT I THINK WE YOU A KIND OF
TRY TO DO AS OPPOSED TO
PRECISION.
I THINK THE ULTIMATE GOAL WOULD
BE REALLY TOWARDS GETTING MORE
PRECISION CARE APPROACH LIKE
ANKIT SAID WHERE YOU CAN KIND OF
INTEGRATE ALL THIS DATA TOGETHER
AND REALLY FIGURE OUT WHAT WORKS
BEST FOR THE PATIENTS.
I THINK THE STUFF WE'RE DOING
NOW IN TERMS OF, OH, THE WOMAN
LIKES A DELL APPLIANCE BETTER
THAN CPAP OR SOMETHING, I THINK
THAT'S PART OF PERSONALIZED
MEDICINE, I THINK WE ALL
PRACTICE THAT OR TRY TO, BUT I
EVENTUALLY IT WOULD BE NICE TO
GET TO A MORE DECISION BASED
GOAL I WAS GOING TO MAKE.
>> THANK YOU.
SO I'M GOING TO HAND OVER TO
ANKIT AFTER SUSHMITA'S COMMENT.
THANK YOU.
>> THANK YOU.
I JUST WANTED TO ADD TO THAT
ABOUT THE METRICS, AND IN
THINKING ABOUT WHAT WAS
PRESENTED YESTERDAY AND NISHA'S
DATA, THE ONE SLIDE ABOUT HOW
MANY WOMEN HAVE BEEN INCLUDED IN
CLINICAL TRIALS.
TO DATE, I DON'T THINK WE REALLY
KNOW A LOT YET ABOUT WHAT METRIC
IS BEST IN PARTICULAR IN WOMEN.
I THINK THOSE DESERVE FURTHER
EVALUATION.
OBVIOUSLY IT'S A BALANCE BETWEEN
GETTING TOO MUCH AND
OVERDIAGNOSING VERSUS
UNDERDIAGNOSING AND MISSING A
LOT OF CLINICALLY RELEVANT
INDIVIDUALS WHO MIGHT RESPOND,
SO I THINK WE'RE STILL LEARNING
A LOT CERTAINLY IN WOMEN AND IN
PREGNANCY, SO I TEND TO KEEP MY
MIND OPEN IN THAT PARTICULAR
POPULATION.
I'M NOT SURE IF WE KNOW
EVERYTHING YET.
>> GREAT.
I THINK OVERALL, THIS SEEMS TO
BE HEADING IN THE RIGHT
DIRECTION WHERE EVEN AT THE END
OF THIS SEMINAR, WE'LL BE ABLE
TO DEFINE PERSONALIZED VERSUS
PRECISION, I THINK THAT WILL BE
HELPFUL TO THE PATIENTS.
ONE OF THE QUESTIONS I HAD FOR
THE PANELISTS JUST TO SORT OF
KICK OFF THIS THING, IN TERMS OF
THE DIFFERENT DEVICES, THE
WEARABLES AND SO ON THAT ARE
COMING ON AND PEOPLE ARE USING
IT, THE REQUIREMENTS BY FDA ARE
NOT AS RESTRICTIVE OR AS STRICT
AS WE WOULD LIKE IN TERMS OF THE
HETEROGENEITY OF THE DISORDER
AND TAKING THAT INTO ACCOUNT.
ESPECIALLY FOR THE GLUCOSE
MONITORING DEVICES, SO I'M JUST
CURIOUS TO SORT OF HEAR THOUGHTS
FROM PEOPLE WORKING WITH
WEARABLES AND NEW DATA AND SO
ON, HOW USING THESE WEARABLES
AND SO ON THAT PATIENTS OR EVEN
RESEARCH PARTICIPANTS ALWAYS
SORT OF BRING UP TO THE CLINIC
AND TO THE RESEARCHERS SAYING
I'M WEARING THIS FITBIT, CAN YOU
LOOK AT MY DATA, CAN YOU TELL ME
HOW IS MY SLEEP LOOKING, ARE YOU
ABLE TO INTEGRATE THAT INTO MY
CLINIC SORT OF OUT COME AND SO
ON.
SO I'M JUST TRYING TO SORT OF
UNDERSTAND FROM THE PANELISTS
WHAT WOULD ALLOW YOU OR LET YOU
USE THOSE WEARABLES DATA AS WELL
AS CLINICAL OUTCOMES OR RATHER
JUST TELL THE PATIENTS YOU KNOW
WHAT, I DON'T THINK THIS DI VICE
DEVICEIS ACCURATE, YOU SHOULDN'E
LOOKING AT THAT.
>> I THINK THAT'S ONE OF THE
CHALLENGES THAT WE HAVE
CURRENTLY IN THE FIELDS, THAT A
LOT OF THE WEARABLES ARE NOT
REALLY -- DON'T HAVE THE
VALIDATION THAT WE WOULD LIKE.
ONE OF MY COLLEAGUES I WORK
WITH, HE CALLS THEM TOYS.
SO IT HARD TO MAKE GOOD CLINICAL
DECISIONS ON SOME OF THESE
WEARABLES.
IT'S GETTING BETTER, THE APPLE
WATCH IS NOW GOING TO BE
FDA-APPROVED, SO WE'RE MOVING IN
THE RIGHT DIRECTION, BUT I THINK
YOU HAVE TO BE VERY CAUTIOUS IN
TERMS OF WHAT YOU GAIN FROM LIKE
A FITBIT OR A W UH-UH K STRAP OR
WHATEVER IN TERMS OF INTEGRATING
INTO CLINICAL DECISION-MAKING.
HAVING SAID THAT, I THINK THE
FUTURE OF OUR FIELD IS GOING TO
MOVE BEYOND THE SLEEP
LABORATORY.
WE'LL STILL HAVE THE SLEEP
LABORATORY FOR CAREFUL
PHYSIOLOGY AND FOR SELECTED
PATIENTS, BUT IN ORDER TO REALLY
IMPLEMENT THERAPY, YOU KNOW,
IT'S A BOTTLENECK.
>> I'LL LET ESRA KNOW AND THEN
ARI, YOU CAN GO.
>> I AGRA WITH WHAT DR. STROLLO
SAID, BUT I THINK IN MY
PRESENTATION WHAT I SHOWED ABOUT
SORT OF THIS METRIC THAT CAN
CHANGE OUR THINKING OR HOW WE
DEFINE TREATMENT ADHERENCE WAS
BASED ON WEARABLES, SO PEOPLE
WHO USE THEIR MASKS AND JUDGED
UPON THEIR MASK ON TIME-BASED ON
OUR CURRENT CRITERIA, MANY OF
THEM ARE WEARING FITBIT, MANY OF
THEM ARE WEARING DIFFERENT
WEARABLES.
AND TO INTEGRATE THAT
INFORMATION INTO OUR THERAPIES
IS -- TO ME IS REALLY
FUNDAMENTAL.
WE HAVE A TREATMENT HERE, IT MAY
WORK FOR SOME POPULATION, OF
COURSE WE HAVE DIFFERENT
MODALITIES FOR SLEEP APNEA
TREATMENT TODAY.
BUT WE DO NOT HAVE THE CORRECT
DOSE FOR THIS.
WE KNOW THE CORRECT DOSE IS THE
NIGHTLY SLEEP DURATION.
IT'S JUST ALMOST PRESCRIBING AN
ASTHMA INHALER, TELL THE
PATIENT, PRESS AS MANY PUFFS AS
YOU CAN.
IT'S ALMOST LIKE GIVING A BLOOD
PRESSURE PILL ARBITRARILY
BECAUSE ASSUMING THE BEDTIME IS
EIGHT HOURS TO TELL THEM FOUR
HOURS IS ENOUGH.
SO I THINK THAT WE NEAT TO --
MOVE BEYOND THIS SO WE CAN MAKE
IMPACT AND INFLUENCE TO OTHER
DISCIPLINES LIKE CARDIOLOGY, I
THINK WE NEED TO REALLY MOVE
FORWARD WITH OUR THINKING OF HOW
DEFINING OUR ADHERENCE TRACKING.
AND WHERABLES WHERE WEARABLES A
FANTASTIC WAY TO ACHIEVE THAT.
>> WEARABLES PROVIDE A VERY
POWERFUL OPPORTUNITY TO OBTAIN
OBJECTIVE MEASUREMENTS IN THE
ENVIRONMENT THAT THE PATIENT IS
IN, BUT I ALSO WANT TO PUT A
COUNTER POINT THAT I PERSONALLY
FEEL THAT WHEN WE COMBINE ALL
WEARABLES TOGETHER AND THINK OF
THEM AS A WHOLE, WE WOULD NOT
MAKE PROGRESS AND WE NEED TO
THINK OF WEARABLES WITHIN A
SPECIFIC DOMAIN.
WHAT I MEAN BY THAT, IF WE WANT
TO THINK OF, LET'S SAY, GLUCOSE,
WHICH IS MY AREA OF EXPERTISE,
WE'LL LOOK AT THE CONTINUOUS
GLUCOMONITORS AND WE CAN TALK
WITHIN THAT DOMAIN WHAT IS AN
ACCEPTABLE AND NOT ACCEPTABLE
MEASURE, AND HOW WE CAN USE IT.
AND USING THE CPAP MACHINE, THAT
IS ANOTHER SPECIFIC DOMAIN WE
ARE TALKING ABOUT AND WE CAN
TALK ABOUT WHETHER THE
MEASUREMENTS WE GET SUFFICIENTLY
ACCURATE OR NOT, SUSHTLY
ACCURATE.
WHEN WE TALK ABOUT THE BLOOD
PRESSURE, TOLD YOU THE SAME
THING, WHEN WE TALK ABOUT THE
PHYSICAL ACTIVITY, IT WOULD BE
THE SAME THING.
SO I FEEL LIKE WE CANNOT JUST
SPLIT ALL THE WEARABLES
TOGETHER, BUT WE HAVE TO LOOK
SPECIFICALLY WITHIN THE DOMAIN
THAT WE WANT THEM TO MEASURE,
AND THEN EVALUATE WHETHER THEY
CAN BE USEFUL OR NOT USEFUL AND
WHAT IS THE PROGRESS TO BE MADE.
>> DIEGO, GO AHEAD.
>> WHICH I THINK TIES IN VERY
WELL WITH THE PROPOSAL THAT
ANKIT SUGGESTED YESTERDAY ABOUT
HOW WE COULD DEFINE SLEEP APNEA
AS THE SERIES OF DOMAINS THAT
MIGHT BE IMPACTING SLEEP
FRAGMENTATION, MIGHT BE
IMPACTING OXYGEN SATURATION,
MIGHT BE AFFECTING HEART
FUNCTION.
THERE'S MANY DOMAINS.
I THINK WE ALL RECOGNIZE THERE'S
MANY DOMAINS SLEEP APNEA IS
IMPACTING.
IF IN THINKING ABOUT BOTH
DIAGNOSING AND CHARACTERIZING
BUT ALSO MAKING SURE THAT WE'RE
MONITORING THE DISEASE WELL AND
WHAT SORT OF WEARABLE TRACK WHAT
NEEDS TO BE TRACKED FOR THAT
PATIENT, I THINK IF WE SOMEHOW
IDENTIFY WHAT'S THE PRIMARY
DOMAIN THAT'S BEING IMPACTED BY
EACH PATIENT, AND THEN PERHAPS A
SPECIFIC WEARABLE MOVING FORWARD
TO TRACK HOW WELL THEY ARE
MANAGING THEIR DISEASE PROBABLY
WOULD BE ONE WAY TO GO.
>> NAJIB?
>> THIS IS MORE OF A QUESTION
FOR THE PANEL ACTUALLY TO BE
HONEST WITH YOU.
LIKE I READ THESE PSGs, WE GET
ALL THIS INFORMATION AND I FEEL
LIKE I'M ALMOST SCHOOLING MYSELF
INTO THINKING THIS ACTUALLY
REFLECTS WHAT THEY DO AT HOME
AND NUMBER ONE AM I FOOLING
MYSELF INTO THINKING THAT THIS
IS EXACTLY THE SAME AS EVERY
SINGLE NIGHT THEY'VE HAD NOR THE
LAST SIX MONTHS OR LAST FIVE
YEARS OR WHATEVER, AND IT'S BEEN
SHOWN -- LIKE MATTRESSES AND
STUFF ISN'T THAT GREAT, SO PART
OF MY KIND OF THINKS WE GET ALL
THESE THINGS UPDATED, WE CAN
GENERATE ALL THESE METRICS FROM
THE PSG AND WE REALLY KNOW WHAT
THEY'RE DOING THAT NIGHT, I JUST
DON'T KNOW HOW REFLECTIVE IT IS
TO SAY THIS TRULY -- AND THEN BY
THE SAME TOKEN, EVEN THOUGH I
THINK THERE'S ALL THESE ISSUES
WITH WEARABLES, WILL YOU
ACTUALLY GET BETTER DATA IF YOU
JUST GET A LITTLE BIT OF DATA
EVERY DAY BUT YOU COLLECT IT FOR
LIKE THREE OR FOUR MONTH, IS
THAT GOING TO BE BETTER THAN
GETTING A ONE NIGHT PSG, ARE
THEY COMPLEMENTARY?
THAT'S WHY I STRUGGLED WITH AS
WELL WHEN WE'RE COMING UP WITH
ALL THESE METRICS, AND I'M
HOPING THAT AFTER ONE NIGHT OF
PSG, THE PERSON IS GOING TO HAVE
CANCER IN FIVE --
>> I'M GOING TO MAKE A POINT AND
THEN LET BOB GO ON.
SO YOU KNOW, THIS IS SORT OF
MAYBE A CONTRARIAN VIEW AND
MAYBE EVEN CONTROVERSIAL TO SOME
EXTENT, BUT IN THE PURSUIT OF
SORT OF KNOWING MORE AND MORE
ABOUT SLEEP APNEA, HAVE WE PUT
OURSELVES IN A HOLE BY LOOKING
AT SEVERAL DIFFERENT DOMAINS AND
SHOULD A SLEEP APNEA TEST BE
INCLUDED IN SO MANY DIFFERENT
DOMAINS INCLUDING EEG, ECG, THIS
IS YOUR TEST, THIS IS WHAT
YOU'RE GULF COAST TO LOOK AT.
EVEN THOUGH THOSE CARDIAC
PROBLEMS ARE TO SOME EXTENT
GOING TO AFFECT BRAIN FUNCTION
AND OTHER THINGS.
SO HAVE WE IN THE PURSUIT OF
SORT OF KNOWING EVERYTHING WE
WANT TO KNOW ABOUT SLEEP APNEA,
EXPANDED PSG TO SUCH A LARGE
DIMENSION THAT WE NOW DON'T KNOW
WHAT TO DO WITH IT AND ARE
ACTUALLY TRYING TO FIND SIGNAL
AND NOISE AND SORT OF GOING
BEHIND THAT WHEN WE SHOULDN'T BE
DOING THAT?
WHICH IS HAVING THEM SORT OF USE
IT.
SO I'VE MADE THAT POINT AND THEN
LET BOB GO ON.
>> SURE, I THINK I GENERALLY
AGREE WITH WHAT YOU AND MAJIB
SAID.
WHEN I SEE SOMEBODY WHO SLEEPS
IN THE SLEEP LAB FOR 95% OF THE
NIGHT AND THEIR -- THEY'RE
CHRONICALLY SLEEP DEPRIVED AND
THEIR ONE NIGHT IN THE LAB IS
THE BEST NIGHT SLEEP THEY'VE
HAD, AND WE HAVE ALL THESE
THINGS -- WE ALSO DID A STUDY
WHERE WE WERE LOOKING AT WEIGHT
GAIN IN FRESHMAN.
THE ADVANTAGE OF WEARABLES,
WE'RE LOOKING AT SLEEP TIME
WHICH DID GO DOWN, BUT WEIGHT
STAYED THE SAME AND IT BECAUSE
THE WEARABLE ALSO LET US KNOW
THAT THEIR ACTIVITY, THEIR STEP
COUNT DOUBLED WHEN THEY CAME ON
TO CAMPUS AND THEY WEREN'T
DRIVING AND LIVING AT HOME.
SO I'M A BIG FAN OF THE
WEARABLES, YOU HAVE TO HAVE
CAVEATS, BUT THEY'RE MEASURING I
THINK MUCH CLOSER TO WHAT IS
ACTUALLY HAPPENING ON A REGULAR
BASIS.
I THINK THIS IS AN EXCITING TIME
BECAUSE WE ARE GOING TO START TO
GET A LOT OF WEARABLE
INFORMATION THAT'S NOT JUST
ABOUT SLEEP AND BREATHING AND
HEART RATE, BUT ACTIVITY.
PEOPLE WHO HAVE TROUBLE SLEEPING
AT NIGHT, WHAT ARE THEY DOING
DURING THE DAY?
I'M SORT OF PRO WEARABLE, I
THINK WE'RE A LITTLE SLOW ON THE
UPTAKE FOR THESE.
SO I'LL STOP THERE.
I THINK YOUR OTHER COMMENTS,
THOUGH, HOPEFULLY THE OTHER
PANELIST CAN COME ON, THEY'RE
REALLY GOOD.
>> THANKS.
FASCINATING TOPIC.
I THINK WE ALL SEE THE PATIENTS
WHO COME IN AND SHOW US THEIR,
YOU KNOW, THEIR PHONE WITH THEIR
DATA LIKE THIS IS WHAT'S
HAPPENING, I HAVE SLEEP APNEA,
YOU KNOW, DO SOMETHING.
SO YEAH, I AGREE WITH THE NEED
FOR VALIDATION AND OBVIOUSLY THE
TECHNOLOGY IS MOVING SO QUICKLY
SO THAT MAKES IT CHALLENGING
WITH ALL THE NEW DEVICES AND
ALGORITHMS THAT ARE OUT THERE.
JUST TO SAY I THINK THERE IS
SOMETHING DEFINITELY ABOUT NIGHT
TO NIGHT VARIABILITY WITH YOU
WE'VE ALL TALKED ABOUT BEFORE,
AND ALSO ON SLEEP QUALITY, IN
ADDITION TO THE SLEEP APNEA
METRICS, THE SLEEP QUALITY COULD
BE SOMETHING OF VALUE IN
PARTICULAR IF THAT'S VALIDATED.
THE OTHER PIECE IS JUST TO SAY
WHEN WE'RE DOING STUDIES WITH
OUR PATIENT PARTNERS, SOMETHING
THEY'VE ASKED FOR, INCLUDED IN A
VARIABLE AND THEY REALLY LIKE
KNOWING WHAT'S GOING ON.
SO WE'VE LISTENS TO OUR -- WE'RE
GOING TO BE LOOKING AT HOW IT
DETERMINES THEIR ABILITY TO
MONITOR THEIR THERAPY.
SO FOR US, WE'RE LOOKING AT
PREGNANCY WITH ALTERNATIVE
TREATMENT OPTIONS SO NOT JUST
CPAP.
SO COULD BE SOMETHING THAT COULD
BE USEFUL.
I DO AGREE IT NEEDS FURTHER
ALLEGATION WITH RESPECT TO THE
EFFICACY METRICS BUT IT COULD
YIELD SOME IMPORTANT
INFORMATION.
>> I'D JUST LIKE TO MAKE ANOTHER
COUPLE COMMENTS.
SO WE DO MO MOSTLY HOME SLOPE
TESTING QUITE FRANKLY CLINICALLY
AND WHAT I USUALLY TELL
PATIENTS, IS THIS I THINK YOU
GET MORE ACCURATE INFORMATION
THAN PUTTING SOMEBODY ALL WIRED
UP ON THEIR BACK, UNCOMFORTABLE.
IF YOU'RE DOING CAREFUL
PHYSIOLOGY, IT'S ONE THING.
BUT IF YOU'RE TRYING TO FIGURE
OUT A SIGNAL OF WHAT IS ACTUALLY
GOING ON IN THE BEDROOM, I THINK
HOME SLEEP TESTING IS BETTER.
I WAS STRUCK BY ESRA'S DATA WITH
HER APP THAT SHE WAS USING, THAT
YOU CAN HAVE SOMEBODY THAT'S
100% COMPLIANT BUT SLEEPS FIVE
HOURS.
IN PATIENTS THAT WE SEE IF
CLINIC, THAT'S WHERE WI WE REALY
LEVERAGE THE DATA DOWNLOADS.
IT'S NOT UNCOMMON WHEN YOU SEE
SOMEBODY SLEEPING FIVE HOURS A
NIGHT OR EVEN SIX HOURS A NIGHT
AND THEY'RE COMPLAINING OF
SLEEPINESS.
WELL, THAT'S MORE THAN SLEEP
APNEA THAT YOU'RE TRYING TO DEAL
WITH THE PATIENT.
AND YOU CAN GET A LOT OF THAT
INFORMATION FROM THE DATA
DOWNLOADS AND USUALLY PATIENTS
WANT TO INTERACT WITH THAT.
A WEARABLE GIVES YOU, I THINK,
SOME ADDITIONAL INFORMATION IN
TERMS OF SLEEP QUALITY, BUT
AGAIN, MY ONLY CAUTION WOULD BE
THAT YOU HAVE TO MAKE SURE THAT
IT'S ACCURATE INFORMATION.
>> SUSAN?
>> SO JUST TO MAYBE BUILD ON
THAT, THE WAY I KIND OF THINK
ABOUT THINGS A LITTLE BIT IS IT
NEVER EITHER/OR.
AND WHERE I REALLY THINK THE
EXCITEMENT OF TRYING TO BECOME
PRAGMATIC AND GET MORE RELIABLE
WAYS TO PHENOTYPE PEOPLE AND GET
THEM INTO TREATMENT IS USE WHAT
I'LL REFER TO AS OUR DEEP OF
PHENOTYPING WHETHER IT'S PO
POLYSOMOGRPH -- THEY MAY NOT
DIRECTLY TELL US ABOUT THE
MECHANISMS IN THE PATHWAYS, BUT
THEY MAY BE PRACTICALLY BE ABLE
TO BE HARNESSED IN THE REAL
WORLD.
THE KINDS OF WORK THAT EXCITE
ME, I DO THINK SOME OF THE
WEARABLES ARE REALLY
INTERESTING, I THINK ONE OF THE
SIGNALS THAT MANY WEARABLES HAVE
NOW IS THE PPG SIGNAL.
THAT'S A READOUT OF MANY THINGS
INCLUDING POTENTIALLY
SYMPATHETIC INNERVATION AND
VARIATION IN BLOOD PRESSURE AND
PULSE.
AND YOU KNOW, I THINK A REALLY
INTERESTING QUESTION IS QA
FEATURES OF THAT PPG SIGNAL
MIGHT TELL US ABOUT PHENOTYPE X
OR SLEEP APNEA CLUSTER X VERSUS
Y, BECAUSE THAT COULD
POTENTIALLY BE USED WITH SOME OF
THESE WINGS AND WATCHES OVER
MULTIPLE DAYS.
AND I THINK AS A FIELD, WE
EVENTUALLY ARE GOING TO HAVE TO
KNOW THAT MAYBE IT'S NOT ABOUT
ACCURATE -- WE HAVE TO RE-THINK
ACCURACY AS MAYBE PREDICTION.
SO I THINK THE ACCURACY AND THE
MECHANISMS ARE THAT DEEP
PHENOTYPING WORK WE DO, BUT
ULTIMATELY I THINK WE WANT
PRAGMATIC TOOLS TO BE ABLE TO
PREDICT WHO'S AT RISK AND WHO'S
GOING TO RESPOND AND THEY
ACTUALLY MAY NOT BE MEASURING
THE PERFECT PHYSIOLOGIC TRAIT
BUT THEY WILL BE USEFUL
CLINICALLY.
SO I JUST WANTED TO PUT THAT
PITCH OUT.
AND I KIND OF SEE THAT COMING.
AGAIN, I SEE HOW MANY PEOPLE
ACCESS THE NSRR TO LOOK AT SOME
OF THESE DATA, AND I FEEL LIKE
THERE ARE PEOPLE THAT ARE GOING
TO COME OUT WITH SOME REALLY
COOL ALGORITHMS.
>> THERE'S ONE QUESTION FROM THE
VIDEOCAST I'D LIKE TO TAKE, IT
SAYS NICE TO HAVE THESE
PERSONALIZED APPROACHES WITH
COMBINED CLINICAL PHYSIOLOGY,
IMAGING, ALL THE DIFFERENT
DOMAINS.
FROM A RESEARCH PERSPECTIVE, HOW
FEASIBLE WILL THEY BE IN THE
CONTEXT OF LIMITED FUNDING AND
LACK OF A SLEEP NETWORK THAT
OTHERS HAVE SUGGESTED AS SOME OF
THE SOCIETIES ARE BUILDING UP
ON.
BUT WHAT IS OUR IN GENERAL
PERSPECTIVE, HO YOU DO WE SORT
OF -- THESE ALL A.I. APPROACHES
AND SO ON ARE GREAT AND VERY
NOVEL AND EXCITING, BUT HOW DO
WE SORT OF UTILIZE THAT?
I'LL START OUT MAYBE ASKING
DIEGO, ONE OF THE THINGS HIM AND
I LEARNED TOGETHER WAS WHEN WE
WANTED TO USE THESE NEW
GENERATIVE A.I. APPROACHES AND
SO ON, EVERY CALL WE WOULD MAKE
TO THESE LARGE LANGUAGE MODELS
BY FACEBOOK AND OTHER COMPANIES
REQUIRES US TO PAY A LOT OF
MONEY.
NIH HAS SOME OF THE
OPPORTUNITIES SO THERE'S NIH
STRIDES INITIATIVE AND OTHERS,
WHICH OFFER FUNDING FOR SORT OF
USE OF THAT, BUT THERE'S NEVER
GOING TO BE A SITUATION WHERE WE
WOULD BE ABLE TO COMPETE WITH
THESE LARK COMPANIES WHO ARE
TRYING TO UTILIZE ALL THE DATA
AND JUST TO SORT OF PUT FORTH
ANOTHER LITTLE POINT IS,
23ANDME, ALL THEIR GENETIC DATA
IS GOING TO GO TO THE HIGHEST
BIDDER, AND SO WHOEVER HAS THE
COMPUTING POWER CAN ACTUALLY USE
AND UTILIZE IT AS IT IS.
SO WHAT IS YOUR PERSPECTIVE ON
THAT?
>> I THINK THAT'S A VERY
INTERESTING IMPORTANT POINT.
I THINK, YOU KNOW, I THINK YOU
TOUCHED UPON DATA PRIVACY
CONCERNS, WHICH I THINK IT'S
ALSO ANOTHER LEVEL LIKE IT'S
CHALLENGING LIKE WE ALL HAVE
THIS PROSPECT OF USING LLMs TO
REALLY HELP WITH -- ASPECTS, SO
IT'S CHALLENGING TO ALLOW --
TALK TO YOUR INSTITUTION TO SAY
CAN I PUT MY PATIENT'S NOTE INTO
CHATGPT OR LLAMA 3 AND TRY TO
GET SYMPTOM INFORMATION.
SO IT'S NOT AS SIMPLE, WHICH
GOES BACK TO WHAT WE'VE JUST --
WE ARE STILL PROBABLY IN THE
VERY EARLY STAGE OF TRYING TO
DETERMINE HOW EFFECTIVE SOME OF
THOSE TOOLS ARE IN ORDER TO GIVE
US ADDITIONAL INFORMATION THAT
WILL BE RELEVANT, AND PERHAPS
THAT IS AN OPPORTUNITY THERE
EVEN TO ASSESS IN A MORE
SYSTEMATIC WAY, AND THEN ONCE
YOU DEMONSTRATE THAT, WE
DEMONSTRATE THAT IT COULD BE
FEASIBLE, PERHAPS THERE COULD BE
A PACKAGE NOW DEPLOYED IN
DIFFERENT SITUATIONS,
INCORPORATING MORE OF THOSE
SETTINGS IN THE CLIN.
I THINK TECHNOLOGY ALWAYS
EVOLVES MORE RAPIDLY THAN
IMPLEMENTATION, AND I THINK
IT'S -- THAT'S A GOOD THING.
I THINK YOU WANT TO ALWAYS PUSH
THE BRAKES, BUT WE CANNOT REALLY
JUST STOP THE CAR, RIGHT?
SO THAT'S MY PERSPECTIVE ON
THAT.
>> GREAT.
I'LL TAKE THIS QUESTION -- AS
YOU SUGGESTED AND SOME OF THE
OTHER DATA ABOUT SORT OF BEING
IMPORTANT AND THERE'S PROBABLY A
PHENOTYPE AS WELL.
ESSENTIALLY IT IS IMPORTANT TO
DO A LONG TERM MONITORING STUDY
IN PREGNANCY ALONG WITH -- WHEN
WE ARE LOOKING AT ALL THE
EXISTING DATA THAT WAS USED IS
EITHER ONE NIGHT OR TWO NIGHT
BUT NOW WE'RE TALKING ABOUT MORE
LONG TERM MONITORING WITH THESE
NEW WEARABLE DEVICES AND SO ON,
THEY DON'T HAVE THAT INFORMS
THAT HAS ACTUALLY INFORMED US
THE IMPORTANCE OF LOOKING AT
SOME OF THE CHARACTERISTICS.
>> WOW, THAT'S A TOUGH QUESTION.
I HAVE TO SAY, IT'S EVEN A BIT
MORE COMPLICATED IN PREGNANCY
BECAUSE THEY'RE EVOLVING IN
THEIR PREGNANCY AND AS THEY
EVOLVE, THAT FLOW LIMITATION
MAY, IN FACT, CHANGE TO OVERT
HAPPENINGS AND THERE ARE CASE
REPORTS OF THAT, AND WE'VE
CERTAINLY SEE THAT, WHAT DOES
THAT REALLY MEAN, AT WHAT POINT
IS IT RELEVANT, I THES, THIS IS
SOMETHING THAT WE'VE BEEN
PUTTING OUR HEADS TOGETHER FOR
TOM TIME.
AS YOU RECALL I KNOW YOUR GROUP
HAS BEEN DOING WORK IN THIS AS
WELL, WITH INDU AND OF COURSE
NOW THAT THERE'S THIS VALIDATED
ALGORITHM THAT WAS USED IN THE
NEW MOM TO BE COHORT BY RACHEL
AND SCOTT, I THINK IT KIND OF
OPENED OUR EYES A LITTLE MORE AS
TO THE DIFFERENT SIGNALS AND
OUTCOMES, SO I THINK IT'S STILL
VERY EARLY FOR ME, WORKING WITH
RACHEL AND SCOTT AS WELL TO LOOK
THE AT DATA ON GESTATIONAL
DIABETES TO SEE WHAT COMES OUT
OF -- YOU'D KNOW AND THE NEW MOM
TO BE DATA, THERE WAS NO SIGNAL
WITH GESTATIONAL DIABETES, SO
JUST CURIOUS, I THINK WE JUST
NEED MORE ANOUN S ANNOUNCEES.
I DONE KNOW HOW THAT'S GOING TO
BE -- BY WEARABLES AND I DON'T
KNOW IF IT'S SHOULD.
>> SO LET'S LET ESRA TAKE OVER
AND MODERATE SOME OF THE OTHER
QUESTIONS.
>> THANK YOU, ANKIT.
JUST TO COMMENT TO THE EARLIER
COMMENTS THAT DR. STROLLO AND
DR. REDLINE MADE, WHETHER A
PERSON WHO'S UTILIZING THEIR
CPAP FOR FOUR OR FIVE HOURS IS
STILL SLEEPY IN OUR CLINIC, I
THINK THIS REALLY BRINGS THE
POINT ABOUT MULTICOMPONENT
INNINGS VENGS, RIGHT?
SO THEN WE CAN PO BE PERSONALIZG
THIS PATIENT'S TREATMENT.
THAT PATIENT DOESN'T NEED A
POTENTIALLY MORE ADVICE ON
TELLING THEM TO USE C PAT MORM,
AND TAKING INTO ACCOUNT WHETHER
THIS IS A SEX AND GENDER
DIFFERENCES, OW WE'RE GOING TO
APPROACH THAT SLEEP EXTENSION TO
AN OPTIMAL RANGE.
AND SOME OF THESE STUDENTS ARE
DEVELOPING THESE TOOLS, HOW
WOULD YOU OPTIMIZE IN A PERS
PERSON -- THAT HEALTHY BEHAVIOR
THAT'S GOING TO AFFECT PRETTY
MUCH DIFFERENT DOMAINS OF THEIR
LIVES, AND THEN REALLY BALANCING
OUT SOME PHENOTYPEING WITH SOME
PRACTICAL MEASURES, BECAUSE THIS
BRINGS TO THE NEXT SESSION, NEXT
ROUND DISCUSSION THE PATIENTS
ARE NOT ACCEPTING WHAT WE ARE
ASKING THEM TO DO.
IF THEY'RE COMEING WITH THEIR
WEARABLE INFORMATION TO US, IF
THEY'RE ASKING THESE QUESTIONS,
IF THEY WANT TO BE JUST AN N OF
1 TO BE TAKEN CARE OF, THEN WE
NEED TO REALLY, YOU KNOW, DO
THIS.
SO I WOULD LIKE TO ASK IFABLE I
AM OLD-FASHIONED WITH ALL THESE
BLACK CAMERAS, SO IF THE SESSION
5 AND 6 SPEAKERS, IF YOU CAN
TURN ON YOUR CAMERAS, THEN WE
CAN START THE ROUNDTABLE
DISCUSSION.
I SEE KLAR'S CAMERA ON.
I REALLY ENJOYED YOUR TALK,
KLAR.
OBVIOUSLY THESE
PHARMACOTHERAPIES ARE REALLY,
YOU KNOW, MOVING OUR FIELD
FORWARD, AND I WANTED TO ASK
MAYBE TOO GENERAL OF A QUESTION
IS, HOW CLOSE DO YOU THINK WE
ARE TO REALLY THEN BRIDGING TO
THE LAST SESSION, IMPLEMENTING
THOSE TO THE CLINICAL PRACTICE?
>> THAT'S A WONDERFUL QUESTION.
I THINK THESE ROUNDTABLE
DISCUSSIONS WERE A GREAT
ADDITION TO THIS.
I'D LIKE IT MAKE SOME COMMENTS
TO SORT OF BRIDGE PRECISION
MEDICINE, OUR FIELD NOW ENTERING
PHARMACOLOGIC THERAPIES FOR
TREATMENTS FOR OUR PATIENTS, AND
PERHAPS IMPLEMENTATION.
I THINK ONE OF THE THINGS NAJIB
SAID AT THE BEGINNING REALLY
RESONATED.
I ACTUALLY HAVE A FAMILY MEMBER
WHO IS GOING THROUGH BREARS BRET
CANCER TREATMENTS RIGHT NOW AND
I HAVE BEEN BLOWN AWAY WITH WHAT
IS POSSIBLE IN THAT FIELD WITH
RESPECT TO PHENOTYPING AND CARE.
YOU KNOW YOUR STAGE, YOU GET THE
ONCOTYPE OF YOUR TUMOR, YOU'RE
POST-MENOPAUSAL, THIS TRIAL
GIVES YOU THIS THERAPY.
AND IT IS PRECISION MEDICINE ON
STEROIDS, AND I THINK WE CAN
ONLY DREAM OF HAVING THAT KIND
OF DATA AND SCIENCE.
I THINK AS A FIELD AS WE SORT OF
ENTER PHARMACOLOGIC THERAPY FOR
SLEEP DISORDER BREATHING IN
PARTICULAR, I THINK AS
CLINICIANS, WE NEED TO, I THINK,
BE MORE BROADLY THINKING ABOUT
THE CARDIOMETABOLIC MENTAL
HEALTH, COGNITIVE HEALTH OF OUR
PATIENTS, AND ENGAGING IN THAT
CARE.
I THINK THAT MANY OF OUR
COLLEAGUES IN OTHER SPECIALTIES
KNOW ABSOLUTELY NOTHING ABOUT
SLEEP, AND CIRCADIAN SCIENCE.
I THINK WE SEE INCREDIBLY HIGH
RISK PATIENTS IN OUR CLINICS,
WITH CARDIOMETABOLIC DISEASE,
END STAGE COPD, END STAGE HEART
FAILURE, AND THERE IS NO REASON
WHY WE SHOULDN'T BE ENGAGING
THIS.
I THINK OUR HEALTHCARE SYSTEM IS
SO FRAGMENTED RIGHT NOW.
AND THE IDEA OF ONE-STOP
SHOPPING WHERE WE OWN EVERYTHING
RELATED TO SLEEP HEALTH OR
CIRCADIAN HEALTH OF THESE
PATIENTS IS REALLY -- REALLY
APPEALS TO THE SORT OF INTERNIST
IN ME.
I THINK ALSO REGARDING SORT OF
IMPLEMENTATION SCIENCE AND WHERE
WE SHOULD BE MOVING IN THAT
DOMAIN, I PUT THIS IN ONE SMALL
COMMENT IN THE CHAT, AS A.I. IS
COMING ON BOARD FOR SCORING
SLEEP STUDIES, AND I THINK WE'RE
MOVING MORE AND MORE TOWARDS
DOING HO HOME SLEEP TESTING
WEARABLE DEVICES, I THINK ONE
REALLY UNDERREPRESENTED
HEALTHCARE PROVIDER IN OUR FIELD
IS THE SLEEP TECHNOLOGIST.
IT IS EMBARRASSING HOW LITTLE WE
HAVE THIS PROVIDER ENGAGED IN
PATIENT FACING ACTIVITIES.
AS THEY'RE NOT GOING TO BE
NEEDING TO SCORE STUDIES AS MUCH
AND DO OVERNIGHT STUDIES, WE
SHOULD ENROLL THEM IN THE CARE
DAWRNG THE DAY TIME OF OUR
PATIENTS.
AND I THINK ALSO RELATED TO
IMPLEMENTATION SCIENCE, WE NEED
TO START THINKING ABOUT SLEEP
HEALTHCARE ACROSS HEALTH SYSTEMS
RIGHT NOW, AND RIGHT NOW, I
THINK WHAT WE'RE DOING IN
ACADEMIC CENTERS IS SETTING UP
INDIVIDUAL SLEEP LABORATORIES AT
EVERY HOSPITAL, AND THERE'S NO
REASON THAT WE NEED FIVE OR SIX
DIFFERENT SLEEP CENTERS IN A
HEALTHCARE SYSTEM.
I THINK WE NEED MAYBE ONE OR TWO
THAT CAN DO REALLY COMPLICATED
IN-LAB TESTING AND REALLY
EMBRACE THINGS LIKE TELEHEALTH
AND REALLY THINK ABOUT HOW WE
CAN BETTER STREAMLINE THE CARE.
ALL OF OUR SLEEP CENTERS ARE
OVERWHELMED WITH PATIENTS.
WE'RE SPENDING SO MUCH TIME
RIGHT NOW ON ANNUAL VISIT FOR
INSURANCE PURPOSES, AND I THINK
REALLY THINKING CRITICALLY IN
THAT SORT OF HEALTH SERVICES
RESEARCH, ALSO IMPLEMENTATION
SCIENCE, TO ALLOW US TO DO THIS
MORE COMPLICATED CARE IN PATIENT
IS WHERE WE NEED TO GO.
>> THANK YOU, KLAR.
I SEE SEVERAL HANDS UP.
BOB?
>> I WANTED TO GO BACK, SO
BEFORE KLAR JUST RAISED A WHOLE
BUNCH OF GREAT QUESTIONS WHICH I
ALSO HAVE QUESTIONS ABOUT, IN
THE CHAT, ESRA, YOU ASKED
ACTUALLY ABOUT THE
PHARMACOTHERAPY FOR OSA AND YOU
ASKED ABOUT SOME OF THE NEWER
STUDIES AND THE INCREASE IN
HEART RATE.
KLAR, YOU SAID HEY, WE USED
THESE DRUGS AND WE'RE GOING TO
MONITOR PEOPLE.
BUT ARE YOU GOING TO TREAT
PEOPLE WHO DON'T HAVE SYMPTOMS
AND YOU'LL SAY WELL, THE AHI IS
BETTER, BUT NOW I'VE INCREASED
THE HEART RATE, ARE YOU GOING TO
TREAT PEOPLE WHO ARE TRYING TO
MINIMIZE THEIR CARDIOVASCULAR
RISK TO GET THE AHI LOWER BUT
GET THE HEART RATE UP?
MY SENSE IS THERE ARE PATIENTS
IN WHOM THOSE DRUGS ARE GOING TO
BE USEFUL, BUT IT'S GOING TO BE
SYMPTOMATIC PEOPLE, BUT I'M
ASSUMING YOU'RE NOT GOING TO
PRESCRIBE THESE DRUGS TO TREAT
THE SLEEP APNEA TO REDUCE
CARDIOVASCULAR RISK AT LEAST
BASED ON THE STUDIES WE HAVE
NOW.
BUT I'M CURIOUS, I DON'T KNOW
HOW I'M GOING TO USE THESE DRUGS
COMPLETELY IF THEY ARE APPROVED.
>> I'M CURRENTLY NOT PRESCRIBING
ANY OF THAT'S DRUGS FOR THE CARE
OF SLEEP APNEA, THE NOR
ADRENERGICS OR THE
ANTIMUSCARINICS.
THE HEART RATE GOES UP -- ON
SOME OF THESE, THAT IS
ABSOLUTELY THE CASE.
SO WE NEED TO FIGURE OUT WHICH
TARGET POPULATION BENEFITS FROM
THESE SPECIFIC NOW MULTIPLE
PHARMACOLOGIC OPTIONS.
I THINK MY POINT TO ESRA'S
POINT, I THINK IT'S TRUE, BUT
MANY OF THESE THERAPIES ARE IN
WIDESPREAD USE, MANY OF OUR
PATIENTS ARE COMING IN ON THESE
TREATMENTS, YOU THINK THE
ADDERALL, WITH THE OVERLAP OF
ADHD, IT'S A NOR ADRENERGIC.
AND WE SHOULD BECOME MORE
FAMILIAR WITH THEIR USE AND HOW
DO YOU MONITOR THEM ON THESE
MEDICATIONS.
>> I'D LIKE TO JUST FOLLOW UP ON
THAT, KLAR.
WE WERE TALKING ABOUT
HETEROGENEITY IN OUR PATIENT
POPULATION.
BUT YOU KNOW, WHAT I'M SEEING
NOW IS OLDER AND OLDER PATIENTS
COMING IN AND THEY MAY BE ON A
STIM LANDSTIMULANT FOR EXCESSIVE
SLEEPINESS AND IT MAKES ME
INCREMENTALLY NERVOUS TO GIVE
THEM SOMETHING THAT'S GOING TO
POTENTIALLY HAVE AN ADVERSE
CARDIOVASCULAR IMPACT.
WE REALLY HAVEN'T STUDIED THESE
DRUGS THAT WELL IN THE ELDERLY.
THAT'S A VULNERABLE POPULATION.
THE QUESTION I HAD FOR YOU,
THOUGH, IS, THAT WAS A GREAT
REVIEW OF WHAT'S ON THE HORIZON
IN TERMS OF ANTIOBESITY DRUGS,
BUT ONE IN THE THINGS IN THE
V.A. THAT'S GOING ON RIGHT NOW
IS THERE'S THIS THING CALLED THE
VASER TRIAL WHERE THEY'RE
LEVERAGING PHARMACOGENOMICS TO
IDENTIFY THE BEST DRUG FOR A
GIVEN PATIENT USING THE GENOMIC
SIGNATURE.
AND YOU KNOW, WHEN WE ONLY HAD
CPAP AND ORAL APPLIANCES,
PHARMACOJEA KNOW MIX WAS NOT A
THING, BUT I THINK THAT IS GOING
TO BE AN OPPORTUNITY FOR US AS
WE GET MORE AND MORE DRUGS IN
THE TREATMENT SPACE, AND I JUST
WANTED TO GET YOUR REACTION TO
THAT AS A NOTION.
>> I THINK THE V.A. HAS BEEN A
LEADER IN SO MANY WAYS WITH
MILLION VETERAN PROGRAM AND WE
HEARD ABOUT SOME OF THE SCIENCE
IN SLEEP THAT WAS COMING OUT OF
THAT TODAY.
I THINK THE CARE IS OUTSTANDING
AT THE VA.
WITH LIMITED RESOURCES.
I THINK IN ADDITION TO
PHARMACOGENETICS, I THINK SOME
VERY INTERESTING QUESTIONS FOR
OUR FIELD ARE THAT WE'RE JUST
STARTING TO TOUCH ON IS THE IDEA
OF CHRONOTHERAPEUTICS, WHEN DO
WE TIME ALL OF THESE DIFFERENT
MEDICATIONS.
THERE'S SOME NASCENT LITERATURE
ON ANTI HYPERTENSIVES MAY BE
MORE EFFECTIVE AT NIGHTTIME,
CHOLESTEROL MEDICATIONS, THAT'S
REALLY IMPORTANT SCIENCE WE NEED
TO BE ENGAGING WITH AS WELL.
SO ALL OF THIS, I THINK
HOPEFULLY WILL MOVE US TOWARDS
MORE PRECISION-BASED APPROACHES.
>> I'LL GIVE YOU ONE ANECDOTE, I
SAW A PATIENT A FEW WEEKS AGO
WHO HAD LIVER CIRRHOSIS AND
PORTAL HYPERTENSION AND WAS
DOSING WITH A BETA-BLOCKER IN
THE MORNING AND WAS FALLING
ASLEEP.
HE STOPPED TAKING THE
BETA-BLOCKER AND WAS FINE.
I SAID HAVE YOU TRIED TAKING IT
AT NIGHT?
IF YOU'RE SLEEPY?
AND YOU KNOW, THAT WAS NOT PART
OF THE CONVERSATION THAT HE HAD
WITH HIS HEPATO LOGIST.
I THINK YOU'RE RIGHT, TIMING AND
CIRCADIAN RHYTHM ALIGNMENT WITH
NOW DRUGS THAT WE HAVE WOULD BE
AN IMPORTANT PART OF THE SLEEP
HOME FOR TOTAL CARE.
VERY GOOD.
>> TURNING TO MAYBE DAVID AND
CHRISTOPHER TO THE -- RELATED TO
SESSION 5, WHAT ARE YOUR
THOUGHTS HOW CLOSE WE ARE TO
IMPLEMENTING SOME OF THE REALLY
EXCITING THERAPEUTICS YOU SHOWED
IN YOUR PRESENTATIONS?
AND THEN HOW WOULD THIS
INFLUENCE PATIENTS' PERCEIVED
CARE AND CAREGIVERS?
WE HAD A LITTLE BIT OF THAT
DISCUSSION BUT MAYBE TO EXPAND
ON THAT.
>> AND MAYBE JUST WITH REGARDS
TO THE NASOPHARYNGEAL STENT, I
THINK THE POPULATIONS THAT WERE
UTILIZING IT ARE SOME OF THE
MOST COMPLEX CHALLENGING
POPULATIONS, AND SO NATURALLY
THE QUESTION AROSE, WELL, HOW
ABOUT OTHERWISE HEALTHY ADULT OR
MORE RUN OF THE MILL OBSTRUCTIVE
SLEEP APNEA.
SO THAT'S SOMETHING WE'RE REALLY
INTERESTED IN PURSUING SOME
ADDITIONAL EXTRAMURAL FUNDING
FOR.
INTERNALLY, WE HAVE A PILOT
STUDY THAT WE'RE GOING TO
INITIATE JUST FOR KIND OF THE
ADULT OBSTRUCTIVE SLEEP APNEA.
AND THEN AGAIN, WE'RE IN YEAR
FOUR OR FIVE OF OUR SINGLE SITE
TRIAL, SO WE'LL BE REALLY
EXCITED TO ANALYZE THAT DATA AND
WORKING WITH THE FDA ACTIVELY,
AND I THINK THAT THE NATURE OF
THE DEVICE BEING NON-SURGICAL
AND EASY TO MONITOR, EASY TO
KIND OF REMOVE OR REMEDY IF
THERE'S ANY CONCERNS, MY HOPE IS
THAT DISCUSSION IN PROCESS WITH
THE FDA IS RELATIVELY EXPEDIENT.
>> I THINK JUST BROADLY WE'RE
POISED T TO DO IT.
IF YOU THINK ABOUT THE
COMPONENTS THAT ARE NEEDED, YOU
LOOK AT PEOPLE ON THE SCREEN
HERE, LIKE DR. HONAKER AND
DR. WILLIAMSON WHO ARE
PSYCHOLOGISTS THAT DEAL WITH A
LOT OF EXPERTISE IN BEHAVIORAL
SLEEP MEDICINE AND THEN ALSO
HAVE REALLY TAKEN A LARGE
INTEREST IN OBSTRUCTIVE SLEEP
APNEA OUTSIDE OF THE PHYSICIANS
THAT ARE TREATING, GETTING
DIFFERENT PERSPECTIVES.
THAT'S PART OF THE WAY THAT
SLEEP MEDICINES AND PEDIATRICS
HAS PRACTICED.
IN TERMS OF IMPLEMENTATION, IF
YOU LOOK WITHIN OUR VERY, VERY,
VERY SMALL FIELD, WE BRING OTHER
PEOPLE IN LIKE OTOLARYNGOLOGISTS
LIKE DR. ZOPF AND THEN OUR
COLLEAGUES KIND OF ACROSS THE
SPECTRUM INCLUDING THE
SPECIALISTS THAT MANAGE
PRIMARILY THESE VERY COMPLICATED
PATIENTS THAT WE SEE.
AND THEN THE OTHER COMPONENT I
THINK IS JUST GENERATING THESE
NETWORKS.
PEOPLE LIKE DR. REDLINE THAT
HAVE REALLY BEEN ABLE TO BRING
TOGETHER MULTIPLE SITES THAT ARE
ABLE TO RECRUIT PATIENTS INTO
THESE MULTICENTER STUDIES
STARTSTARTING WITH CHAD AND SOMF
THESE OTHER TRIALS, IT BEEN HUGE
TO BE ABLE TO HAVE THESE NETWORK
OF SITES THAT CAN DO THAT KIND
OF WORK.
THEN THE NEXT STAGE WOULD BE
THEN TRYING TO ROLL IT OUT TO
POTENTIALLY LIKE SMALLER SITES,
UPLOOKING INTERNATIONALLY, AND I
THINK AGAIN, JUST REFERENCE THE
INCLUDE NETWORK WHICH I THINK IS
REALLY STARTING TO PUSH THESE
KIND OF NETWORKS THAT INCLUDE
PATIENTS THAT ARE OTHERWISE KIND
OF HARD TO RECRUIT.
SO I THINK LEVERAGING SOME OF
THESE TECHNIQUES AND THESE
NETWORKS ARE FORMED WITH LIKE
SOME OF THE OTHER PEOPLE IN THIS
GROUP THAT HAVE EXPERTISE IN
IMPLEMENTATION SCIENCE AND HAVE
AN INTEREST IN PEDIATRICS, DOING
SOME OF THE SAME WORK YOU'VE
ALREADY DONE POTENTIALLY IN THE
ADULT WORLD IN CHILDREN, I THINK
WE'RE REALLY POISED TO MAKE SOME
HUGE STRIDES IN THIS AREA, IT'S
REALLY EXCITING TO HEAR A LOT OF
THE TALK IN THAT SESSION TODAY.
>> THANK YOU.
I'M DEFINITELY FULLY, AS MANY OF
YOU WOULD AGREE FOR
INTERDISCIPLINARY RESEARCH AND
COLLABORATION FOR SURE.
THERE ARE EXAMPLES FROM OTHER
FIELDS THAT WHEN A DIABETES
TRIAL COMES OUT, IT'S HUGE
SAMPLE SIZES DUE TO THE
MULTICENTRIC NATURE OF IT,
SIMILAR WITH CARDIOVASCULAR
DISEASES.
SO SARAH, DO YOU HAVE ANY
COMMENTS ABOUT SOME OF THE TOOLS
YOU'VE BEEN USING TO TRIGGER A
PATIENT'S INTEREST OR TO SORT OF
TRY TO ADDRESS THE DI SPAIRTS IS
IN DETECTING SLEEP APNEA AND
TREATING?
>> YEAH, SO I THINK THAT OTHERS
HAVE ALLUDED TO THIS QUITE A BIT
BUT I THINK IT'S VERY, VERY MORE
THAN TO WORK WITH THE
STAKEHOLDERS WHENEVER YOU'RE
DEVELOPING A NEW TOOL.
SO THAT FIGURE TOORK TOOK US ABA
YEAR AND A HALF, THEY DIDN'T
LIKE THIS EMOJI, WE WORKED VERY
CLOSELY WITH PCPs AND PARENTS
AND SLEEP MEDICINE PROVIDERS FOR
ACCURACY.
WITH THE COMPUTER DECISION
SUPPORT SYSTEM, WE ALWAYS PILOT
IT IN ONE CLINIC, AND CHANGE A
LOT OF THINGS AND WE ALWAYS HAVE
GROUPS OF PCPs LOOK AT IT AND
EVERY TIME WITHOUT FAIL THAT WE
ENGAGE STAKEHOLDER, WE LEARN
SOMETHING IMPORTANT THAT HELPS
IT BE SUCCESSFUL.
BUT IT IS SLOW WORK, AND SO I'M
REALLY EXCITED ABOUT DISCUSSIONS
THAT WE'RE HAVING ABOUT ANYTHING
THAT CAN HELP US, I GUESS,
COLLABORATE AND SYSTEMS THAT CAN
HELP US BE MORE EFFICIENT.
>> I'M CURIOUS, BECAUSE WE HAD
VERY LITTLE EXPERIENCE WITH THIS
USER CENTERED DESIGN THAT WE DID
FOR THE TOOL I PRESENTED, THE
APP.
DO PATIENTS MORE LEAN TOWARDS
SIMPLICITY?
GOING BACK TO OUR KEYNOTE
SPEAKER, DR. PUNJABI'S KEYNOTE
SPEAKER, FOR EXAMPLE IF YOU WANT
TO PRESENT THEM WITH SO MANY
DIFFERENT METRICS ON THEIR APP
ABOUT THEIR RESIDUAL AHI AND
MASK LEAK AND THEY JUST WANTED
TO SEE A SIMPLE CIRCLE AND A
PERCENT GOAL SO DO YOU FEEL LIKE
WHEN YOU'RE DEVELOPING SOME OF
THESE SURVEYS THAT THIS IS YOUR
IMPRESSION?
>> I THINK THAT A LOT OF TIMES
IT IS SIMPLER MESSAGES THAT TEND
TO RESONATE, AND I DON'T THINK
THAT MAKES THEM WORSE, IT'S JUST
MORE RELATABLE.
SO FOR EXAMPLE ONE OF THE FIRST
CHANGES WE MADE IS WE TOOK ANY
REFERENCE TO OBSTRUCTIVE SLEEP
APNEA OUT OF OUR EDUCATION
MATERIALS BECAUSE WE IMMEDIATELY
GOT A LOT OF QUESTIONS ABOUT
WHAT'S OBSTRUCTIVE SLEEP APNEA
AND HOW IS THAT DIFFERENT THAN
SLEEP APNEA AND WE SAID OKAY,
WE'RE JUST GOING TO TAKE OUT
OBSTRUCTIVE AND IT JUST PLAIN
SLEEP APNEA.
SO YOU DON'T KNOW IF YOU DON'T
ASK.
>> ANY OTHER QUESTIONS?
>> I THINK WHAT YOU'RE GETTING
AT, ESRA, IS THE WHOLE NOTION OF
HEALTH LITERACY THAT WE DIDN'T
SPECIFICALLY TALK ABOUT BUT IS
IMPORTANT WHEN DESIGNING ANY
SORT OF INTERVENTION.
MY COLLEAGUE AT THE -- AT
UNIVERSITY OF WEST VIRGINIA THAT
I'M FORTUNATE TO BE HIS MENTOR
FOR ON HIS K AWARD IS LOOKING AT
HEALTHCARE DELIVERY IN RURAL
POPULATION, AND THE LOW
SOCIOECONOMIC GROUP THAT'S AT
HIGH RISK, AND I WAS GLAD THAT
KLAR SHOWED THAT WEST VIRGINIA
IS STILL NUMBER ONE IN OBESITY,
SO ROB'S WORK IS GOING TO BE
VERY IMPORTANT, HOPEFULLY HE'LL
SHOW SOME OF THAT WORK AT A
SUBSEQUENT WORKSHOP.
BUT ONE OF THE THINGS THAT WE'VE
BEEN DOING WITH STAKEHOLDERS AND
IN ROLLING OUT IS PROGRAM IS
REALLY TRYING TO ASSESS NOT ONLY
SOCIOECONOMIC STATUS BUT HOW
THAT ALIGNS WITH HEALTH LITERACY
WHEN DEVELOPING MATERIALS, WHICH
I THINK SARAH WAS GETTING AT IN
HER COMMENTS.
>> I SEE A COUPLE OF HANDS,
DR. WILLIAMSON?
>> HI, THANKS SO MUCH FOR THESE
AWESOME TALKS.
THIS WHOLE WORKSHOP HAS BEEN
REALLY INFORMATIVE AND I'M SO
EXCITED TO HEAR ABOUT ALL THE
GREAT DIRECTIONS PEOPLE ARE
PURSUING.
YOU KNOW, I THINK WHEN WE'RE
THINKING ABOUT HOW WE IMPLEMENT
ACROSS CONTEXT AND WE KIND OF
TAKE THINGS INTO ACCOUNT LIKE
HEALTH LITERACY AND
SOCIOECONOMIC STATUS BUT ALSO
MORE OF AN INTERSECTIONAL LENS
AND THINKING ABOUT ALL THE
DIFFERENT IDENTITIES THAT PEOPLE
HOLD, I OFTEN THINK ABOUT IT
LIKE YOU'RE LOOKING INTO ONE OF
THOSE FUN HOUSE MIRRORS WHERE
THERE'S LIKE JUST -- YOU COULD
ADAPT FOREVER, AND I THINK
THAT'S A CHALLENGING SCIENTIFIC
QUESTION WHEN WE THINK ABOUT
LIKE DOES EVERY ADAPTATION NEED
AN EVALUATION, AND I THINK ON
THE FLIP SIDE, AS PEOPLE HAVE
SAID EARLIER TODAY, REALLY THERE
IS NO IMPLEMENTATION WITHOUT
ADAPTATION, SO PART OF THIS I
THINK IS MAKING SURE WE'RE
OPTIMIZING FEATURES OF
INTERVENTIONS AS WELL AS
IMPLEMENTATION STRATEGIES THAT
CAN BE APPLIED DIFFERENTIALLY
ACCORDING TO THE PATIENT AND THE
CONTEXT.
SO THERE'S SOME MENTAL HEALTH
RELATED WORK THAT LOOKS AT, YOU
KNOW, CLINICIAN DECISION-MATION
MAIKING AROUND HOW TO MAKE
EVIDENCE-BASED CULTURAL
ADAPTATIONS.
SO I THINK WE CAN APPLY A LOT OF
THOSE FRAME WORKS TO SOME OF
WHAT WE'RE TALKING ABOUT HERE.
SURE, THERE ARE LIKE BROAD
THINGS WE CAN DO TO MAKE SURE
THAT HEALTH LITERACY FROM THAT
PERSPECTIVE SL ACCESSIBLE, BUT I
THINK, TOO, ABOUT REALLY
TRAINING CLINICIANS AND
IMPLEMENTERS IN HOW WE MAKE
THOSE DECISIONS IN AN
EVIDENCE-BASED WAY SO IT CAN BE
MORE APPLICABLE AS WE SCALE.
>> THANK YOU.
WE HAVE ABOUT FOUR MINUTES, SO
MAYBE QUICKLY GOING THROUGH
RAISED HANDS.
SUZIE?
OH, YOU'RE MUTED.
YOU'RE MUTED.
>> SORRY.
I'M JUST GOING TO ECHO SOME OF
THE COMMENTS MADE BY
DR. WILLIAMSON AND STROLLO IN
TERMS OF THINKING MORE ABOUT
IMPLEMENTATION STRATEGIES AND
IMPLEMENTATION GAPS IN CLINICAL
CARE.
I KNOW WE TALKED ABOUT THE LAST
TWO DAYS ABOUT HOW MUCH IS
UNKNOWN AND AS A CLINICIAN, I
AGREE, I THINK IT WAS IN THE
COMMENTS ABOUT I JUST FEEL LIKE
WE HAVE A LITTLE BIT LIKE A CAVE
WOMAN, LIKE WE HAVE CPAP, WE
HAVE DEVICE, DO YOU EVEN HAVE
SLEEP APNEA?
THERE'S SO MUCH WE DON'T KNOW.
BUT AT THE END OF THE DAY, WE
STILL HAVE A LOT OF PEOPLE USING
CPAP IN MANDIBULAR DEVICES WHO
ARE DOING WELL, AND I THINK WE
CAN THINK ABOUT IMPLEMENTATION
STRATEGIES EVEN WITH THE DATA WE
HAVE ON SEVERAL EFFECTIVE
TREATMENTS, AND THAT SOME OF THE
GAPS ARE JUST RIGHT IN FRONT OF
US, SO WE KNOW HEALTH LITERACY
IS A PROBLEM AND WE'VE DONE WORK
WITH PATIENT ADVOCACY GROUPS
SUCH AS MONICA'S ASAP GROUP, AND
SOME OTHER PATIENTS, THEY WANT
JUST MORE INFORMATION AND WE
HAVEN'T REALLY THOUGHT ABOUT
TAILORING INFORMATION AS WAS
SPOKE ABOUT AND QUESTIONS OF THE
INTERSECTIONALITY AND HOW TO
ACTUALLY GET -- BRING PATIENTS
TO THE TREATMENT.
WE TALKED ABOUT HOW WHY PAP IS
SO BAD AND HOW THERE MAY BE BOTH
BIOLOGICAL AND SOCIAL FACTOR,
BUT AT THE END OF THE DAY,
PAP -- ARE NOT THAT FAR BELOW
ANTIHYPERTENSIVE USE.
WE DO HAVE SEVERAL JUST EMERGING
STRATEGIES SO I THINK WE SHOULD
CONTINUE TO PUSH THE SCIENCE, AS
IMPERFECT AS IT MAY BE, AND
REALIZE WE HAVE TOOLS NOW THAT
WE CAN IMPLEMENT TREATMENTS WE
HAVE ACROSS THE PERIOD.
AND I'LL JUST SORT OF TAKE PAT'S
COMMENT ABOUT HEALTH LITERACY,
WE NEED HEALTH LITERACY IN OUR
CLINIC IN URBAN, IN BOSTON, WE
NEED MORE HEALTH LITERACY, WE
NEED BETTER PATIENT EDUCATION,
BECAUSE THOSE ARE ALL FACTORS
THAT INFLUENCE IMPLEMENTATION AS
WELL AS THE MULTIPLE HANDOFFS
AND CARE GAPS.
WE OBVIOUSLY NEED A BETTER
SYSTEM OF CARE, AND IT WOULD BE
NIGHNICE TO SEE HOW SOME OF THEK
WE TALKED ABOUT TODAY CAN
INFLUENCE THAT, BUT WE HAVE THE
FIELD -- SOME IMPLEMENTATION
DISSEMINATION SCIENCE THAT I
THINK CAN REDUCE SOME OF THOSE
CURRENT GAPS THAT WE ALREADY
HAVE ENOUGH EVIDENCE FOR.
SO THAT'S JUST MY LITTLE PITCH
AT THE END.
>> THANK YOU.
WE ARE OUT OF TIME, SO I'M GOING
TO GIVE THE MICROPHONE TO
ALFONSO FOR CLOSING REMARKS, BUT
THANK YOU, EVERYONE.
ALFONSO.
>> YES, THANK YOU, EVERYBODY,
AND SORRY TO CUT OFF THIS GREAT
DISCUSSION.
SO I JUST WANT TO TAKE A COUPLE
MINUTES HERE AT THE END TO GIVE
THANKS TO ALL OF YOU FOR
PARTICIPATING IN THIS WORKSHOP.
I THINK WE CAN ALL AGREE, WE
HEARD A LOT OF GREAT TALKS OVER
THE LAST COUPLE DAYS AND I THINK
WE'VE GAINED SOME VALUABLE
INSIGHTS AND A LOT OF NEW
QUESTIONS ABOUT THE COMPLEXITIES
OF OSA AND THE CRITICAL NEED TO
INCORPORATE PATIENT PREFERENCES
IN A PERSONALIZED MEDICINE AND
EFFICIENTLY PRECISE APPROACHES
TO OSA DIAGNOSIS AND TREATMENT.
DISCUSSIONS AROUND THE IMPACT OF
SEX AND RACIAL DIFFERENCES, THE
APPLICATION OF PERSONAL
PERSONALIZED APPROACHES AND THE
ROLE OF EMERGING TECHNOLOGIES
LIKE A.I. HAVE UNDERSCORED THE
IMPORTANCE OF TAILORING CARE
AMONG DIVERSE POPULATIONS AND
ACROSS THE ENTIRE LIFECOURSE,
INCLUDING FOR SEX AND GENDER
DIFFERENCES BUT ALSO INCLUDING
PEDIATRIC POPULATIONS AND DURING
LIFE TRANSITIONS LIKE PREGNANCY
AND MENOPAUSE, AND AMONG
INDIVIDUALS WITH DEVELOPMENTAL
AND INTELLECTUAL DISABILITIES
INCLUDING AS WE HEARD TODAY
THOSE WITH DOWN SYNDROME.
WE ALSO EXPLORED THE CHALLENGES
OF TRANSLATING RESEARCH INTO
CLINICAL PRACTICE AND THE NEED
FOR IMPLEMENTATION SCIENCE TO
ENSURE EFFECTIVE REAL WORLD
APPLICATION.
SO MOVING FORWARD, YOU KNOW, IT
SEEMS CLEAR THAT THERE ARE A LOT
OF RESEARCH OPPORTUNITIES IN
ADDRESSING THESE KNOWLEDGE GAPS
AND UNMET NEEDS WILL LIKELY BE
KEY TO IMPROVING OUTCOMES FOR
INDIVIDUALS WITH OSA.
SO LASTLY, I'D LIKE ON BEHALF OF
NCSDR AND COLLEAGUES ACROSS
NHLBI AND NIH, I WANT TO GIVE A
BIG THANKS TO ALL THE SPEAKERS,
DISCUSSANTS AND MODERATORS FOR
VOLUNTEERING THEIR VALUABLE TIME
TO PARTICIPATE IN THIS WORKSHOP.
I ALSO WANT TO THANK OUR
WORKSHOP SUPPORT TEAM,
PARTICULARLY BRITTANY AND SHAWN
FOR HELPING THEM RUN THE LAST
TWO DAYS AND FOR THEIR EFFORTS.
AND FINALLY, I WANT TO GIVE A
HUGE SHOUT OUT AND SINCERE THANK
YOU TO ALL THREE OF OUR
CO-CHAIRS FOR THEIR TREMENDOUS
CONTRIBUTIONS.
YOU HAVE NO IDEA THE TIME AND
EFFORT THEY PUT INTO THE
PLANNING OF THIS WORKSHOP OVER
THE LAST YEAR OR SO.
THE DEDICATION AND EFFORT REALLY
HELPED DRIVE THE DEVELOPMENT OF
THIS WORK SHOM SHOP T WORKSHOP .
THANKS AGAIN TO EVERYONE FOR
ATTENDING AND WE'LL BE IN TOUCH
SOON ABOUT DIFFERENT THINGS THAT
MAY COME OUT OF THIS WORKSHOP.
I HOPE EVERYONE HAS A GREAT
EVENING AND A RESTFUL WEEKEND.
>> THANK YOU.
THANKS, ALL.
>> THANK YOU, EVERYONE.
>> BYE.