GOOD AFTERNOON, I'M JON LORSCH,
DIRECTOR OF THE NATIONAL
INSTITUTE OF GENERAL MEDICAL
SCIENCES, WELCOME TO THE STETTEN
LECTURE, HONORING THE THIRD
DIRECTOR OF NIGMS WITH A STRONG
COMMITMENT TO BASIC SCIENCE,
ESPECIALLY RESEARCH AND
GENETICS, CELLULAR, MOLECULAR
BIOLOGY AND CHEMISTRY, SPENT
MOST OF HIS CAREER AT NIH
SERVING IN TWO INSTITUTES,
OFFICE OF THE DIRECTOR, AND WAS
PARTICULARLY WELL KNOWN AS
CO-AUTHOR OF THE EARLY EDITION
OF TEXT BOOK PRINCIPLES OF
BIOCHEMISTRY.
IN RECOGNITION OF HIS MANY
CONTRIBUTIONS, WITHIN AND
OUTSIDE OF NIH, HE HAS THE
DISTINCTION OF HAVING TWO
ENTITIES NAMED AFTER HIM AT NIH,
THIS LECTURE AND THE DEWITT
STETTEN JR. MUSEUM OF MEDICAL
RESEARCH.
SALLY JOINED THE DISTINGUISHED
LIST OF LECTURERS, DIRECTOR OF
WEST VIRGINIA CTSI, ASSOCIATE
VICE PRESIDENT FOR CLINICAL AND
TRANSLATIONAL RESEARCH,
PROFESSOR OF MEDICINE AT WEST
VIRGINIA UNIVERSITY.
SALLY WORKS TO ALLEVIATE HEALTH
DISPARITIES IN RURAL AMERICA
ESPECIALLY REGARDING PUBLIC
HEALTH CRISES LIKE THE COVID-19
PANDEMIC AND OPIOID CRISIS.
SHE WILL HIGHLIGHT WVCTSI
DEVELOPMENTS INCLUDING RESULTS
FROM A STUDY USING DEEP BRAIN
STIMULATION.
SHE WILL DISCUSS RESEARCH
RESULTS RELATING TO EPIDEMIOLOGY
OF SARS-COV-2 AND TREATMENT OF
THE DISEASE.
SALLY RECEIVED A B.A. IN
CHEMISTRY, AND M.D. FROM CASE
WESTERN RESERVE SCHOOL OF
MEDICINE, NIGMS SUPPORTED HER
WORK THROUGH THE U54 CLINICAL
AND TRANSLATIONAL RESEARCH
AWARDS THROUGH THE INSTITUTIONAL
DEVELOPMENT AWARD, IDeA
PROGRAM, SINCE 2012.
AS OF THIS AUGUST, SALLY WAS
NAMED SCHOOL'S INAUGURAL
CHANCELLOR PREEMINENT SCHOLAR
CHAIR IN RECOGNITION OF HER
OUTSTANDING ACHIEVEMENTS.
SO SALLY, CONGRATULATIONS FOR
THAT EXTREMELY WELL-DESERVED
HONOR.
PLEASE HELP ME WELCOME SALLY FOR
HER TALK, BIOMEDICAL RESEARCH IN
RURAL AMERICA, MUCH
ACCOMPLISHED, MUCH TO DO.
>> THANK YOU FOR THE KIND
INTRODUCTION.
I WOULD JUST LIKE TO THANK DR.
LEY AND DR. LORSCH FOR INVITING
ME, I'M PROFOUNDLY PRIVILEGED TO
PRESENT THIS LECTURE IN HONOR OF
DR. STETTEN, WHO PARTICULARLY
WAS COMMITTED TO GENETICS AND
MOLECULAR AND CELLULAR BIOLOGY,
REALLY THE DISCIPLINES THAT HAVE
CONTRIBUTED SO MUCH TO
TREATMENTS AND CURES OF MANY OF
TODAY'S ILLNESSES.
THIS TALK IS ABOUT RESEARCH IN
RURAL AMERICA, AND WHY IS THAT
IMPORTANT?
IF YOU LOOK IN THE 19th
CENTURY, ACTUALLY MORTALITY
RATES WERE HIGHER IN THE CITIES
AND URBAN AREAS, AND THAT WAS
BECAUSE OF CONTAGION AT
POPULATED AREAS, POOR WATER
SUPPLIES, AND A LACK OF SEWAGE
TREATMENT.
AS SCIENCE REALLY MADE CLEAR
WHAT WE NEEDED TO DO, WATER WAS
CLEAN, THERE WERE SANITATION
PRACTICES PUT IN PLACE, AND IN
THE 20th CENTURY A LOT MORE
VACCINES SUCH THAT BY THE
MID-20th CENTURY, THE
MORTALITY RATES BETWEEN RURAL
AND URBAN POPULATIONS WERE
ESSENTIALLY THE SAME.
BUT AS THIS SLIDE SHOWS ON THE
LEFT PANEL, IN THE LATE '80s,
THESE MORTALITY RATES BEGAN TO
DIVERGE, WITH URBAN RATES
SHOWING IN THE BLUE LINE
CONTINUING TO DECREASE WHILE THE
RURAL RATES SHOWN IN THE GOLD
LINE REALLY FLATTENED OUT.
YOU MIGHT SAY, WELL, THIS IS
JUST -- THIS HAS TO DO WITH
POVERTY, ON THE PANEL OF THE
RIGHT YOU SEE CERTAINLY POVERTY,
HIGH POVERTY COMMUNITIES HAVE
HIGHER MORTALITY RATES, IN FACT
THAT DOES NOT ANSWER THE
DISPARITY.
IN FACT, LOW POVERTY RATE RURAL
COMMUNITIES HAVE SIMILAR
MORTALITY RATES TO HIGH POVERTY
RATE URBAN COMMUNITIES.
NEXT SLIDE PLEASE.
TO TAKE YOU TO WEST VIRGINIA,
WEST VIRGINIA MORTALITY RATE WAS
NUMBER ONE IN THE COUNTRY, A
COUPLE YEARS AGO.
HOWEVER, IT'S BEEN SURPASSED BY
MISSISSIPPI, NONETHELESS AS
SHOWN BY THE MAP OF WEST
VIRGINIA COUNTIES, EVERY COUNTY
IN WEST VIRGINIA HAS A
MORTALITY, AGE ADJUSTED, GREATER
THAN THE U.S. RATE.
SHOWN ON THE RIGHT ARE A NUMBER
OF CONDITIONS AND, AGAIN, THE
WEST VIRGINIA MORTALITY RATE IS
HIGHER.
COVID-19 IS NOW THE THIRD MOST
COMMON CAUSE OF DEATH IN THE
UNITED STATES, ACTUALLY FOR THE
THIRD YEAR RUNNING, AND YOU CAN
SEE HERE AGAIN WEST VIRGINIA IS
ABOVE THE U.S. RATE.
NEXT SLIDE.
WHAT I'M GOING TO TALK ABOUT
TODAY ARE TWO THINGS, NUMBER
ONE, THE CORONAVIRUS PANDEMIC
NATIONAL INITIATIVES ACROSS THE
CTRs, AND SOME WEST VIRGINIA
INITIATIVES, AND THEN THE LAST
COUPLE MINUTES I'M GOING TO TALK
ABOUT SOME OF THE WORK WITH
SUBSTANCE USE DISORDERS AROUND
EMERGENT INFECTIONS RELATED TO
INTRAVENOUS DRUG USE AND
INNOVATIVE TREATMENT.
NEXT SLIDE.
NEXT SLIDE PLEASE.
THE NATIONAL COVID COHORT
COLLABORATIVE IS AN ANALYTICS
PLATFORM THAT COLLECTS
ELECTRONIC MEDICAL RECORD DATA
FROM PROVIDERS ACROSS THE
NATION, HARMONIZES IT, MAKES IT
AVAILABLE TO RESEARCHERS.
REALLY VERY EARLY IN THE
CORONAVIRUS PANDEMIC, THE SPRING
OF 2020, GMS AND THE IDeA
PROGRAM FUNDED CTRs, EIGHT
CTRs INITIALLY INVOLVED TO BE
PART OF N3C TO SUBMIT DATA AND
THEN TO DEVELOP THE
INFRASTRUCTURE FOR THE ANALYTICS
TO ANALYZE THOSE DATA WITH
REALLY SPECIAL FOCUS ABOUT
POPULATIONS FOR WHICH THOSE
CTRs SERVED.
ON THE MAP, YOU CAN SEE THE
INITIAL CTRs ARE IN A LIGHTER
GREEN.
IT WAS MAINE, RHODE ISLAND,
DELAWARE, WEST VIRGINIA,
MISSISSIPPI, OKLAHOMA, NEBRASKA.
HAWAII AND PUERTO RICO AND
VERMONT JOINED AS DID A DAKOTA,
DATA SUBMITTED BY A COBRA IN
SOUTH DAKOTA.
HOWEVER, THE CTR IN NORTH DAKOTA
IS ENGAGING INVESTIGATORS.
IN WEST VIRGINIA WE HAD ONE OF
OUR PARTNER SITES, CHARLESTON
AREA MEDICAL CENTER IN THE
SOUTHERN PART OF THE STATE,
WHERE MORTALITY RATES ARE
HIGHER, HIGHEST, SUBMITTING DATA
AS WELL.
NEXT SLIDE.
AN EARLY PROJECT NOW PUBLISHED
IN JOURNAL OF RURAL HEALTH
ASSESSED MORE THAN A MILLION
COVID-19 PATIENTS FROM ACROSS
THE UNITED STATES, FROM JANUARY
202020 JUNE 2021.
REALITY WAS DETERMINED BY
RURAL/URBAN COMMUTING AREAS
CODES, THAT CLASS CLASSIFY CODES USING
DENSITY, URBANIZATION, DAILY
COMMUTING.
NEXT SLIDE.
THESE ARE KAPLAN-MEIER THAT SHOW
SURVIVAL ESTIMATES.
PURPLE LINE ARE URBAN RUCA
CODES, GREEN LINE ARE RURAL RUCA
CODES ADJACENT TO URBAN AREAS,
AND YELLOW ARE NON-ADJACENT
RURAL RUCA CODES.
MORTALITY, AS YOU CAN SEE, IN
RURAL AREAS IS GREATER THAN
URBAN AREAS, 40% GREATER.
WHICH IS QUITE AN AMOUNT.
YOU CAN SAY SURE, BECAUSE PEOPLE
IN RURAL AREAS ARE OLDER,
FATTER, THEY HAVE MORE
COMORBIDITIES, ALL THOSE WERE
ADJUSTED FOR, RESULTS WERE THE
SAME, EVEN FOR SOCIAL
DEPRIVATION, BEGS THE QUESTION
WHY, WE DON'T HAVE A GOOD
ANSWER.
THE RIGHT PANEL INTERESTINGLY
SHOWS OTHER HOSPITALIZED
PATIENTS WHO DID NOT HAVE
COVID-19, AND YOU CAN SEE THAT
THEIR RURAL INDIVIDUALS HAD AN
INCREASED MORTALITY, IT WAS
ABOUT 20% GREATER AS WELL.
NEXT SLIDE.
A SECOND PROJECT WITH THE NC
3GROUP, THEY SPAN 12 INTUITIONS.
WE LOOKED AT COMMUNITY RISK FOR
BREAK THROUGH INFECTIONS AMONG
FULLY VACCINATED ADULTS, LOOKED
AT IMPACT OF DEMOGRAPHICS,
VACCINE MANUFACTURER, ALSO
RURALITY, AGAIN THESE WERE
ELECTRONIC HEALTH RECORDS
BETWEEN JANUARY 1 AND DECEMBER
OF 2021.
NEXT SLIDE.
THIS IS BASELINE CHARACTERISTICS
TO GIVE YOU AN IDEA OF WHAT THE
POPULATIONS WERE IN EACH OF THE
BUCKETS.
AGAIN, IT WAS URBAN, RURAL THAT
ARE URBAN ADJACENT, NON-URBAN
ADJACENT.
YOU CAN SEE AS YOU MIGHT, YOU
KNOW, HAVE GUESSED THAT THE
RURAL POPULATIONS ARE OLDER.
THAT THE VACCINATION RATES ARE
LOWER, AND THE LAST ROW REALLY
SHOWS THE, YOU KNOW, COMPOSITION
IN EACH OF THOSE ACROSS THE FOUR
REGIONS OF THE U.S.
NEXT SLIDE.
THIS I SHOW BECAUSE I THOUGHT IT
WAS INTERESTING, IF YOU LOOK AT
THE VACCINE MANUFACTURER,
ACTUALLY THE MODERNA VACCINE,
mRNA VACCINE, HAD A LOWER,
SIGNIFICANTLY LOWER BREAKTHROUGH
RATE THAN PFIZER.
THERE HAVE BEEN OTHER STUDIES
THAT LOOKED AT THIS OTHER WAYS,
SUGGESTING PERHAPS THE MODERNA
VACCINE MIGHT BE A BIT BETTER.
THERE HAVE BEEN HYPOTHESIS WHY
THAT MAY OR MAY NOT BE TRUE.
THE OTHER THING THAT IS NOT
SURPRISING, HOWEVER, IS IF YOU
HAD A PREVIOUS HISTORY OF
SARS-COV-2 INFECTION, YOU WERE
LESS LIKELY TO HAVE
BREAKTHROUGH.
AND THAT, YOU KNOW, IN THE
OMICRON PERIOD, YOU WERE MORE
LIKELY TO HAVE BREAKTHROUGH
CONSISTENT WITH WHAT WE KNOW
ABOUT THE INCREASED
TRANSMISSIBILITY.
NEXT SLIDE.
THIS WAS REALLY THE
MULTI-VARIABLE HAZARD RATIOS,
AND AGAIN YOU SEE THAT URBAN
ADJACENT RURAL AND NON-ADJACENT
RURAL COMMUNITIES HAD
SIGNIFICANTLY -- WERE
SIGNIFICANTLY MORE LIKELY TO
HAVE BREAKTHROUGH INFECTIONS.
ALSO, IF YOU LOOK AT VACCINATION
RATES STRATIFIED BY LOW, MEDIUM,
HIGH, AS DEFINED ON THE SLIDE,
YOU CAN SEE SLOW VACCINATION
RATES AREAS WERE MORE LIKELY TO
HAVE BREAKTHROUGH INFECTIONS.
AND I THINK THIS IS REALLY
IMPORTANT BECAUSE, YOU KNOW,
THERE ARE PARTS OF SOUTHERN WEST
VIRGINIA WHERE THE RATE IS 35%,
AND I THINK THIS MIGHT BE REALLY
IMPORTANT TO DISCUSS WITH
COMMUNITIES THE IMPLICATIONS OF
THIS STUDY BECAUSE EVEN THOUGH
YOU'RE VACCINATED, IF YOU'RE IN
A COMMUNITY WITH A LOW
VACCINATION RATE, YOU ARE MUCH
MORE LIKELY TO GET A
BREAKTHROUGH INFECTION THAN IF
YOU WERE IN A COMMUNITY WITH
HIGHER VACCINATION RATE.
NEXT SLIDE.
THIS JUST IS INTERESTING.
IT'S REALLY THE CUMULATIVE
INCIDENCE, AGAIN, YOU KNOW,
RURAL IS THE PURPLE AND RED,
BLUE IS URBAN.
YOU CAN SEE EARLY ON RIGHT AFTER
VACCINATION THERE'S NOT MUCH OF
A DIFFERENCE.
BUT OF COURSE WE KNOW THAT AS
YOU PROCEED OUT OVER TIME FROM
VACCINATION, OVER, YOU KNOW,
MONTHS, FOUR OR FIVE, SIX
MONTHS, ANTIBODY WANES, THAT'S
WHEN YOU START TO GET REALLY AN
INCREASE IN THE INFECTION,
SUGGESTING THAT, YOU KNOW, EVEN
IF YOU GOT VACCINATED, AS YOUR
ANTIBODY LEVELS WANE, YOU'RE IN
COMMUNITIES THAT PEOPLE AREN'T
VACCINATED WITH A LOT OF
TRANSMISSION, YOUR CHANCES OF
GETTING INFECTED ARE GREATER AS
WELL.
NEXT SLIDE.
ANOTHER PROJECT THAT THE CTRs
UNDERTOOK WITH THE N3C PLATFORM
WAS TO DEVELOP AN ORDINAL SCALE
FOR COVID DISEASE SEVERITY.
THE W.H.O. DEVELOPED AN ORDINAL
SCALE TO USE WITH CLINICAL
TRIALS, MOST CLINICAL TRIALS
WITH COVID USED THAT SCALE.
THERE'S LESS GRANULARITY OF DATA
WITH EHRs, AND SO THE W.H.O.
SCALE DIDN'T WORK VERY WELL.
USING ALMOST ACROSS 3 MILLION
PATIENTS, IF YOU GO TO THE NEXT
SLIDE, YOU'LL SEE THE ORDINAL
SCALE FOR EHR USE IS SHOWN ON
THE LEFT, AND REALLY STRATIFIED
PATIENTS BY OUTPATIENT,
HOSPITALIZED, ANY OXYGEN.
WE COULDN'T -- THE W.H.O. REALLY
LOOKED AT, YOU KNOW, OXYGEN BY
MASK OR HIGH SWELL OXYGEN.
IT WAS VERY DIFFICULT IN THE EHR
TO REALLY SORT OF PARSE THAT
OUT.
ECMO WITH A LEVEL OF 9 AND DEATH
WAS 11.
NEXT SLIDE.
AS YOU SEE OVER 28 DAYS AFTER
DIAGNOSIS OF SARS-COV-2
INFECTION, THAT MOST OF THE
PEOPLE DO WELL.
YOU MIGHT SAY, WELL IF THESE ARE
HOSPITALIZED PATIENTS, HOW COME
ON DAY 1 YOU HAVE SOME OF THEM
IN THE PEACH COLOR WHICH IS
OUTPATIENT BUT SOME DID NOT GET
ADMITTED UNTIL LATER, SOME WERE
ADMITTED EARLIER, GOT DISCHARGED
VERY QUICKLY.
THIS IS A COMPOSITE ACROSS THOSE
PATIENTS.
IF YOU LOOK AT THE PANEL ON THE
LEFT YOU SEE THE MORTALITY AS
YOU MIGHT EXPECT GOES UP AS THE
SEVERITY INDEX INCREASES, THE
EXCEPTION IS THAT THE ECMO
PATIENTS STILL HAD A HIGH
MORTALITY OF 25%, BUT THE
MECHANICALLY VENTILATED PATIENTS
WERE ALMOST AT 30%.
I THINK THAT ACTUALLY THIS MAKES
SENSE.
INDIVIDUALS WHO WERE FELT TO
HAVE A VERY POOR PROGNOSIS WERE
NOT PUT ON ECMO, AND DURING THE
DELTA WAVE THERE WAS REALLY
RATIONING OF THE ECMO.
IN FACT, SOME PLACES, YOU KNOW,
PATIENTS OVER 40 OR HIGH BMI
WERE NOT PUT ON ECMO.
IT'S NOT SURPRISING THOSE FOLKS
WITH POOREST PROGNOSIS COLLECTED
IN THE MECHANICAL VENTILATION
GROUP WITH A SLIGHTLY HIGHER
MORTALITY.
NEXT SLIDE.
NOW, THAT ORDINAL SCALE THEN
PERMITTED US TO REALLY LOOK AT
WHAT'S THE BEST THERAPY FOR
TREATMENT OF COVID.
YOU KNOW, THAT WAS A QUESTION
PARTICULARLY EARLY ON.
THIS STUDY REALLY USED MACHINE
LEARNING, NEURAL NETWORK,
MACHINE LEARNING CLASSIFIERS.
AND IT'S INTERESTING BECAUSE
MACHINE LEARNING MODELS ARE
USUALLY CONSIDERED BLACK BOX
PROCEDURES.
YOU HAVE LIMITED INSIGHT, OTHER
THAN SORT OF OUTCOME PREDICTION.
BUT MORE RECENTLY, USE OF
SHEPLEY ADDITIVE EXPLANATION
VALUES, SHAP VALUES AS WE CALL
THEM, CAN PROVIDE INSIGHT INTO
INTERPRETATIONS OF COMPLEX
MACHINE LEARNING MODELS, WITH
HIGH ACCURACY AND ROBUSTNESS.
SHAP VALUES WERE USED.
WHAT THIS STUDY LOOKED AT IS
WHAT IS PROTECTIVE OF HOSPITAL
DISCHARGE?
SO WOULD THERAPY HAVE SORT OF
PREDICT OUTCOME OF DISCHARGE,
AND WHAT FACTORS PREDICT DEATH?
I'LL START WITH THE BAR GRAPH ON
THE RIGHT, THOSE WERE NEGATIVE
IMPACTS.
IF YOU LOOK DOWN THE LIST, MANY
OF THEM ARE PATIENT FACTORS SUCH
AS AGE AND COMORBIDITIES.
THE ONE TREATMENT THAT APPEARS
THERE IS ANTI-COAGULATION
THERAPY.
AND I THINK THAT'S AN
INTERESTING FINDING, AND THE
QUESTION IS WHY ONE MIGHT
HYPOTHESIZE THAT INDIVIDUALS WHO
ONLY GOT ANTI-COAGULATION
PERHAPS HAD A SEVERE
THROMBOEMBOLIC COMPLICATION THAT
REQUIRED THAT TREATMENT.
WE KNOW COVID IS ASSOCIATED WITH
THAT.
THE OTHER MIGHT BE THAT
INDIVIDUALS WHO HAD
COMORBIDITIES SUCH AS DIABETES
PERHAPS PHYSICIANS WERE NOT
GIVING THOSE PATIENTS STEROIDS.
IF WE NOW LOOK AT THE POSITIVE
IMPACTS, WHAT WAS PREDICTIVE OF
HOSPITAL DISCHARGE, YOU CAN SEE
THERE ARE A LOT OF TREATMENTS
THERE, BUT MOST OF THEM ARE
COMBINATIONS.
THE ONLY ONE THAT APPEARS ALONE
ARE STEROIDS.
YOU HAVE ANTICOAGULANTS WITH
STEROIDS.
ANTICOAGULANTS WITH TARGETED
ANTI-VIRALS.
SUGGESTING THAT REALLY
COMBINATION THERAPY AND COVID
MIGHT BE VERY IMPORTANT.
AS YOU KNOW, OUR CLINICAL TRIALS
EARLY ON WERE JUST LOOKING AT
ONE FACTOR.
AS THE PANDEMIC PROGRESSED,
STEROIDS, ANTI-COAGULATION, WERE
NOT EXCLUSIONARY FACTORS.
I THINK THAT THIS IS REALLY
INTERESTING AND MAY INFORM
CLINICAL TRIALS AND HOW WE LOOK
AT THEM.
THE OTHER THING I WOULD SAY
ABOUT THE VERY LARGE DATABASE,
NO CLINICAL TRIAL, YOU KNOW, HAS
INDIVIDUALS IN EVERY
SUBPOPULATION, BUT WHEN YOU HAVE
MILLIONS AND MILLIONS OF FOLKS
YOU CAN BEGIN TO LOOK AT
OUTCOMES IN SPECIFIC
SUBPOPULATIONS OF INDIVIDUALS
WITH PARTICULAR COMORBIDITIES.
NEXT SLIDE.
A SECOND MACHINE LEARNING
PROJECT IN THE CTR N3C GROUP,
WHAT WAS THE POSSIBILITY OF
DISCHARGE WITH TREATMENTS AND
TREATMENT COMBINATIONS, AGAIN
MACHINE LEARNING TECHNIQUES WERE
USED.
AND THE STUDY POPULATION AS YOU
SEE THERE WAS NORTH OF 248,000
FOLKS.
AND THE TOP ONE RESULTS, SOME
ARE NOT SURPRISING, AS THE
CHARLESTON COMORBIDITY INDEX
INCREASED, LOOKING AT COMPOSITE
SCORE OF VARIOUS COMORBIDITIES.
INTERESTINGLY, MECHANICALLY
VENTILATED PATIENTS HAD OUTCOMES
DURING THE OMICRON WAVE THAT
WERE BETTER, REGARDLESS OF THE
THERAPEUTIC REGIMEN THAN WITH
OTHER WAVES.
THIS PERMITTED US, AND I'LL SHOW
A SLIDE IN A MINUTE, LOOKING AT
PRE-DELTA WAVE, DELTA VARIANT
WAVE, AND THEN OMICRON.
OVERALL THE BEST THERAPY WAS
SPIKE PROTEIN MONOCLONAL
THERAPIES WITH ANTICOAGULANTS.
THESE ARE REALLY PANELS
REGENERATED THEM FOR EVERY
ORDINAL SEVERITY LEVEL ACROSS
ALL THE WAVES.
I JUST SELECTED FOR BREVITY
THOSE PANELS OF OS 3,
HOSPITALIZED PATIENTS WITHOUT
OXYGEN REQUIREMENT.
YOU CAN SEE YOU HAVE THE KEY OF
THE VARIOUS TREATMENTS ON THE
SIDE, GOING ACROSS THE X-AXIS
ARE INCREASING CHARLESTON
COMORBIDITY INDEX, SO CLEARLY
CHANCES OF DISCHARGE DECREASED
AS NUMBER OF COMORBIDITIES
INCREASED.
YOU CAN SEE THAT FOR MOST OF
THESE MONOCLONALS ACTUALLY HAD
THE HIGHEST PROBABILITY OF
DISCHARGE, THOUGH IF YOU LOOK
PRE-DELTA AND DELTA PINK IS
TARGETED ANTI-VIRALS, MOST WAS
WITH REMDESAVIR, PRE-PAXLOVID,
WE WANT TO EXTEND TO LOOK AT
TARGETED ANTI-VIRALS WHICH MOST
WOULD FEEL ARE BETTER.
NEXT SLIDE.
I WANT TO JUST BEFORE I LEAVE
THE NATIONAL INITIATIVES REALLY
JUST SAY HOW IMPORTANT THE N3C
INITIATIVE WAS BECAUSE WHAT IT
DID, IT REALLY FACILITATED
PRODUCTIVE COLLABORATION ACROSS
CTRs.
WE REALLY LIKED WORKING WITH
EACH OTHER, IT WAS ONE OF THE
MOST INTELLECTUALLY STIMULATING
THINGS PERSONALLY THAT I WAS
DOING.
AND SO WE ACTUALLY KENTUCKY HAD
FOLKS CTSA WORKING WITH US ON
N3C.
WHEN THE OPPORTUNITY CAME FOR
THE RECOVER STUDY, THE
OBSERVATIONAL COHORT OF LONG
COVID, WE APPLIED SAYING IT WAS
IMPORTANT FOR CENTERS THAT WERE
SERVING UNDERSERVED POPULATIONS
TO REALLY MAKE AVAILABLE STUDIES
IN THOSE POPULATIONS AS WELL.
MANY OF WHICH HAD BEEN HARD HIT
BY COVID.
WE WERE FUNDED.
TWO CTSA, KANSAS AND KENTUCKY,
PARTS PATED IN THE ISCORE
RESEARCH.
LIGHTER GREEN AREAS, TENNESSEE,
OHIO, PENNSYLVANIA, ARE REALLY
CATCHMENT AREAS, JUST SHOWING
THAT REALLY A LARGE PORTION OF
THE UNITED STATES IS REALLY
COVERED BY THIS NETWORK.
WE'VE BEEN A TOP ENROLLER,
OVERENROLLED ADDITIONAL TARGETS,
ADDITIONAL FUNDED STUDIES ARE
NOW BEING IMPLEMENTED.
IMMULINA IS AN IMMUNE MODULATOR,
UNIVERSITY OF MISSISSIPPI
PROCURED FUNDING FOR A PILOT
STUDY ACROSS 12 OF OUR SITES.
AND DR. ROSEN AT MAINE MEDICAL
CENTER, CO-P.I. OF THE ISCORE
NETWORK IS BEING FUNDED.
WE DON'T HAVE A GRANT NUMBER YET
BUT TO LOOK AT THE PATHOBIOLOGY,
ASSESS VIRAL PERSISTENT IN FAT
TISSUE, THERE'S SOME PRELIMINARY
DATA TO SUGGEST, NUMBER ONE,
THAT OCCURS AND, NUMBER TWO, IT
ALTERS THE BIOENERGETICS OF THE
MITOCHONDRIA.
NEXT SLIDE.
IF WE NOW FOCUS ON WEST
VIRGINIA, NEXT SLIDE, I JUST
WANTED TO POINT OUT THAT THE
PARTNERS ACROSS WEST VIRGINIA
SHOWN IN THE LEFT PANEL HAVE
BEEN CRITICALLY IMPORTANT TO
BEING ABLE TO ADDRESS COVID,
PARTICULARLY THE DEPARTMENT OF
HEALTH AND HUMAN RESOURCES WHICH
IS THE STATE HEALTH DEPARTMENT.
THE PANEL ON THE RIGHT IS REALLY
MUCH OF OUR LABORATORY, SHOWS
OUR PRACTICE-BASED RESEARCH
NETWORK WHICH IS NOW UP TO 129
SITES.
NEXT SLIDE.
THE RAPID ACCELERATION OF
DIAGNOSIS FOR UNDERSERVED
POPULATIONS, RADX-UP, WAS
FUNDED, THE GRANT NUMBER IS
ABOVE, TO REALLY LOOK AT
STRATEGIES TO INCREASE TESTING
AMONG UNDERSERVED AND VULNERABLE
POPULATIONS IN WEST VIRGINIA.
IT HAD A COUPLE OF PARTS.
THE MOST IMPORTANT WAS THAT WE
EMPLOYED MOBILE VANS, ONE OF
WHICH IS SHOWN AT THE RIGHT, TO
DO TESTING.
THESE MOBILE VANS WE WORKED WITH
THE COUNTY HEALTH DEPARTMENTS,
AND WE WOULD FIND AREAS THAT
WERE VERY ACCESSIBLE TO FOLKS IN
THE COUNTY, THESE WERE REALLY IN
RURAL AREAS.
ONE OF OUR SITES WAS A FUNERAL
HOME, I DIDN'T THINK THAT WAS
THE RIGHT MESSAGE, BUT IT WAS
VERY EFFECTIVE.
WE ALSO WORKED WITH OUR PBRN
CLINICIAN.
BACK AT THE BEGINNING OF THE
PANDEMIC, YOU COULDN'T GET
SWABBED.
YOU COULDN'T GET SPECIAL
PROTECTIVE EQUIPMENT.
THE THIRD PARTY PAYERS WERE ONLY
PAYING FOR PCR TESTS FOR
INDIVIDUALS WITH SYMPTOMS SO IF
YOU WERE EXPOSED OR YOU NEEDED A
TEST FOR WORK, YOU WERE OUT OF
LUCK.
AND SO WE REALLY WORKED WITH OUR
PBRN SITES AS WELL TO PROVIDE
TESTING, PROVIDE THEM WITH
TENTS, ONE OF THE MOST IMPORTANT
POINTS THERE WAS WE ACTUALLY HAD
FLEX STAFF THAT WOULD GO AND
TEST AT THOSE SITES.
AND IMPORTANTLY, WE HAD A
COMMUNITIES OF COLOR INITIATIVE,
IT WAS A VAN THAT WORKED WITH
COMMUNITIES OF COLOR, WITH
CHURCHES AND SO FORTH,
CULTURALLY COMPETENT STAFF TO
TEST IN THOSE COMMUNITIES.
IT WAS A POPULATION-BASED STUDY.
WE WANTED TO INTENSIFY TESTING
IN THOSE COUNTIES, WITH A
PREDICTED NEAR TERM INCREASE IN
SARS-COV-2 INCIDENCE, AS
PREDICTED USING THE
INSTANTANEOUS REPRODUCTIVE
NUMBER, AND WE ACTUALLY -- THE
TEAM HAS REALLY REFINED THAT
MODEL, AND HAS BROUGHT IN
VACCINATION RATES AND VARIANTS,
ONE PAPER PUBLISHED, REVISED
AGAIN, HAVE ANOTHER ONE UNDER
REVIEW.
NEARLY 143,000 PCR SARS-COV-2
TESTS WERE CONDUCTED, YOU CAN
SEE THE POSITIVITY RATE THERE, 1
IN 5 OF THE CLINIC SAMPLES, AND
MOBILE VAN SAMPLES, NOT QUITE
20% WAS POSITIVE SO THIS WAS --
I WAS SURPRISED AT THE
POSITIVITY RATE AND THE MAP ON
THE RIGHT, WE TESTED IN EVERY
ONE OF WEST VIRGINIA'S 55
COUNTIES EXCEPT TWO.
THE TWO ARE SHOWN IN WHITE.
THIS WAS REALLY ALL OVER THE
STATE.
WE'VE HAD A PAPER PUBLISHED IN
AGPH, AMERICAN JOURNAL OF PUBLIC
HEALTH, SEVERAL OTHERS BEING
SUBMITTED.
TESTING DATA, THE STATE HEALTH
DEPARTMENT WAS A GREAT
COLLABORATOR.
AND AGREED TO PROVIDE US TESTING
DATA NOT ONLY, YOU KNOW, WE HAD
OUR RADx RESULTS, BUT ALL OF
THE TESTING DATA THAT CAME TO
THE STATE.
AND WE LOOKED AT THE
RELATIONSHIP BETWEEN TEST SITE
AVAILABILITY AND, YOU KNOW,
LOOKED AT THAT IN THE CONTEXT OF
SOCIAL DEPRIVATION, AND SOCIAL
DETERMINANTS OF HEALTH.
WHAT WE FOUND WHICH WAS NO BIG
SURPRISE, RIGHT, THE MORE SITES,
THE MORE TESTING YOU'LL HAVE.
BUT THAT WAS REALLY AMPLIFIED IN
COMMUNITIES THAT HAD GREATER
ECONOMIC DEPRIVATION.
SUCH THAT IN FUTURE PANDEMICS,
IN FUTURE PANDEMICS THOSE AREAS
WOULD BE, YOU KNOW, THE PLACE TO
PUT TESTING SITES BECAUSE THEY
WOULD INCREASE, YOU KNOW, THE
NUMBER OF TESTS, MORE SO THAN IN
AN AREA THAT HAD A HIGHER
SOCIOECONOMIC LEVEL.
NEXT SLIDE.
I THINK JUST BEFORE I SAY, I'LL
JUST COMMENT, I THINK IT'S
IMPORTANT IF YOU HAVE
AVAILABILITY, PEOPLE DO AVAIL
THEMSELVES OF THE TESTS.
I MEAN, MANY WERE IN VERY, VERY
RURAL SITES.
SO JUST TO SAY, OH, PEOPLE DON'T
BELIEVE IN SCIENCE, DON'T BOTHER
TO TEST THERE, IS NOT THE CASE.
THAT'S NOT WHAT WE FOUND.
ANOTHER INITIATIVE FUNDED BY GMS
SUPPLEMENT SHOWN THERE WAS VIRAL
SEQUENCING.
TO DATE WE'VE SEQUENCED MORE
THAN 17,000 SAMPLES.
THE DISTRIBUTION OF VARIANTS ON
THE LEFT SHOWS FROM WHEN WE
STARTED DOING THIS IN JANUARY OF
2021 THROUGH CURRENT, BUT I
THINK MORE INTERESTING IS THE
PANEL ON THE RIGHT WHICH JUST
LOOKS AT 2022, AND THE OMICRON
VARIANTS.
AND YOU CAN SEE BA 1 IN RED WAS
SUPPLANTED BY BA 2 IN BLUE,
INTERESTINGLY MORE RECENTLY MOST
OF THE VARIANTS HAVE BEEN BA.5
BUT YOU SEE THE ORANGE WHICH IS
BQ, JUST STARTING IN.
IT WILL BE INTERESTING TO SEE
WHAT HAPPENS THERE.
I SHOULD SAY AGAIN THIS IS NOT
ONLY OUR 17,000 SAMPLES FROM
SEQUENCING INITIATIVE, BUT THE
STATE, CDC WAS SEQUENCING,
LABCORP WAS SEQUENCING.
THE STATE, WE WORKED WITH THEM.
THIS ANALYSIS INCLUDES ALL THE
SEQUENCING ACROSS THE STATE OF
WEST VIRGINIA AND ENABLED US TO
MATCH VARIANT SEQUENCES WITH
ELECTRONIC MEDICAL RECORDS IN
THE WVU MEDICAL SYSTEM THAT WE
SUBMITTED TO N3C.
NEXT SLIDE.
ANOTHER WAS LOOKING AT PATTERNS
OF VARIANT EMERGENCE AND THE
QUESTION HERE IS, IS THERE A
CONSISTENT PATTERN BY WHICH NEW
VARIANTS ARE DISSEMINATED?
AND, YOU KNOW, IS THAT A
SUGGESTION WHERE SURVEILLANCE
FOR FUTURE EPIDEMICS SHOULD BE
DONE?
WE LOOKED AT SARS-COV-2 POSITIVE
SAMPLES FROM SEPTEMBER 2020 TO
MARCH 2022 THAT WERE SEQUENCED,
AND WHAT WE USED, WE HAVE A VERY
GOOD GEOSPATIAL GROUP, BUT THEY
ACTUALLY USED AS THE COORDINATES
THE CENTROID OF THE PATIENT'S
ZIP CODE, WE HAD PATIENT
ADDRESSES, AND INTERESTINGLY THE
VARIANTS OF CONCERN WERE USUALLY
INTRODUCED IN THE NORTH AND
TRAVELED DOWN THE INTERSTATES.
I WAS GOING TO SHOW A VIDEO WE
HAVE, BUT I THOUGHT IT WOULD BE
A GLITCH, PROBABLY WOULD HAVE
BEEN.
I HAVE A NUMBER OF JUST THREE
STILLS WITH EACH OF THE
VARIANTS.
GO TO THE NEXT SLIDE.
THIS IS THE ALPHA INTRODUCTION.
AND YOU CAN SEE IT'S HARD TO
SEE, BUT IN THE MORGANTON, THE
NORTH PART, A COUPLE ORANGE
DOTS.
THAT'S WHERE THAT WAS
INTRODUCED.
AND THEN IF YOU LOOK, THAT'S
JANUARY TO APRIL, IT'S NICER ON
THE VIDEO BUT THIS SPREAD DOWN
THE INTERSTATE, SHOWN IN THE
DARK LINES, AND THEN OUT TO THE
RURAL POPULATIONS.
THE OTHER CONCENTRATION THAT
CAME IN THAT WASN'T RELATED TO
THE REST OF WEST VIRGINIA WAS
EASTERN PANHANDLE, A BEDROOM
COMMUNITY OF D.C.
THAT TRANSMISSION PATTERN WAS
REALLY OVER THERE AND DIDN'T
IMPACT RURAL WEST VIRGINIA.
NOW, NEXT SLIDE, IF WE GO TO THE
DELTA VARIANT, WE SEE A SLIGHTLY
DIFFERENT PATTERN, THOUGH THE
INITIAL ONE ON THE LEFT IN APRIL
WAS IN THE NORTH BUT
SUBSEQUENTLY, YOU KNOW, WE
DIDN'T SEE JUST SPREAD DOWN THE
INTERSTATES.
IT WAS SORT OF ALL OVER.
WE SAID, WHAT'S GOING ON HERE?
WHAT HAPPENED WITH DELTA, IF YOU
REMEMBER, IS DELTA REALLY GOT
GOING IN THE SUMMER OF 2021.
I DIDN'T KNOW THIS BUT A LOT OF
WEST VIRGINIA GOES TO MYRTLE
BEACH AND THERE WERE MULTIPLE
CHURCH GROUPS, RURAL AREAS,
GOING AS A GROUP AND CAME BACK
AND HAD MULTIPLE OUTBREAKS OF
DELTA, DIFFERENT THAN WHAT WE
HAD SEEN WITH ALPHA.
IF WE GO TO THE NEXT SLIDE,
OMICRON, YOU CAN SEE THAT,
AGAIN, IT STARTED IN THE NORTH
BUT, YOU KNOW, VERY QUICKLY
CHARLESTON, WHICH IS SORT OF THE
LEFT LOWER AREA, QUICKLY BECAME
INVOLVED.
AT THE SAME TIME THE NORTH
BECAME INVOLVED, THAT EASTERN
PANHANDLE WAS AS WELL.
NOW, IT'S ONLY A MONTH, DECEMBER
TO JANUARY, YOU CAN SEE JUST HOW
QUICKLY OMICRON SPREAD.
SO WE'RE DOING FURTHER ANALYSIS,
PREPARING A PUBLICATION, BUT,
YOU KNOW, OUR SORT OF CONCLUSION
WITH SOME EXCEPTIONS IS BY AND
LARGE YOU COME IN AT MORGANTOWN,
EASTERN PANHANDLE, IT SPREADS
ALONG THE MAJOR ROUTES AND OUT
TO THE RURAL POPULATIONS.
NEXT SLIDE.
JUST THE LAST PROJECT THAT WE
HAD FOR COVID IN WEST VIRGINIA
WAS ANTIBODY STUDY THAT LOOKED
AT ANTIBODY LEVELS FOR COVID-19
IN NURSING HOME STAFF AND
RESIDENTS.
YOU CAN SEE WE HAD MORE THAN
2100.
NEXT SLIDE.
I SHOULD SAY THAT WEST VIRGINIA
DID A GREAT JOB VERY EARLY ON
VACCINATING A WIDE MAJORITY OF
NURSING HOME RESIDENTS.
MANY OF THE STAFF, NOT SO MANY
OF THE STAFF, WHO REFUSED, BUT
IF YOU LOOK AT THOSE THAT WERE
VACCINATED DURING THE DELTA
SURGE, NOT VERY MANY HAD HAD
BOOSTERS, BUT DURING THE OMICRON
SURGE OVER HALF HAD.
IF WE GO TO THE NEXT SLIDE, YOU
CAN SEE THAT IN THE DELTA ERA
INFECTIONS A LOWER ANTIBODY
LEVEL WAS STATISTICALLY
SIGNIFICANTLY DIFFERENT THAN
THOSE THAT DIDN'T GET INFECTED,
SO, YOU KNOW, YOUR -- IF YOU HAD
LOWER ANTIBODY LEVEL YOU WERE
MORE LIKELY TO GET BREAKTHROUGH
BUT NOT THE CASE WITH OMICRON.
CAN YOU SEE THERE'S NO
DIFFERENCE.
THAT'S CONFIRMING THE FACT THERE
IS SIGNIFICANT IMMUNE EVASION
WITH THE OMICRON VARIANT.
NEXT SLIDE.
I JUST WANT TO FINISH UP THE
NEXT FIVE MINUTES OR SO WITH A
DISCUSSION OF SUBSTANCE USE
DISORDER IN WEST VIRGINIA.
NEXT SLIDE.
THIS SHOWS DRUG OVERDOSE
MORTALITY RATES IN THE UNITED
STATES OVER THE PAST TWO
DECADES.
AND YOU CAN SEE THAT THERE'S
BEEN AN EXPLOSION ALL OVER.
AND THERE'S CERTAIN HOT SPOTS IN
CENTRAL APPALACHIA AS WELL AS
AREAS OF THE WEST.
NEXT SLIDE.
IF WE FOCUS ON WEST VIRGINIA,
2020, WEST VIRGINIA HAS BY FAR
THE HIGHEST DRUG OVERDOSE
MORTALITY RATE.
81.4 PER 100,000.
THERE'S NO OTHER STATE THAT IS
EVEN IN THE GREEN WHICH GOES
FROM 67 TO 81.4.
IF WE LOOK BY APPALACHIAN COUNTY
AGAIN YOU SEE THE SOUTHERN PART
OF WEST VIRGINIA AS WELL AS A
BIT OF OHIO, ALONG THE OHIO
RIVER THERE, HAVE THE VERY
HIGHEST OVERDOSE MORTALITY
RATES.
NEXT SLIDE.
NOT SURPRISINGLY, EMERGENT
INFECTIOUS DISEASES RELATED TO
INJECTION DRUG USE HAS BEEN
INCREASING.
NEXT SLIDE.
HEPATITIS C IS ONE OF THEM.
IF YOU LOOK AT THE SLIDE AT THE
LEFT, THIS IS 2013 TO 2015, THE
MOST RECENT THAT THEY HAVE.
YOU CAN SEE THAT FOUR OF THE SIX
STATES WITH THE HIGHEST
PREVALENCE OF CHRONIC HEPATITIS
C ARE IDeA STATES.
HEPATITIS C, YOU KNOW, BY AND
LARGE YOU HAVE ACUTE INFECTION
BUT UNLIKE HEPATITIS B THE
MAJORITY OF INDIVIDUALS WITH
HEPATITIS C WILL DEVELOP CHRONIC
INFECTION.
OF THOSE, ABOUT 10 TO 20% WILL
GO ON TO DEVELOP CIRRHOSIS,
LIVER FAILURE, AND CIRRHOSIS IS
ASSOCIATED WITH HIGHER INCIDENCE
OF HEPATOCELLULAR CARCINOMA.
EIGHT, NINE YEARS AGO, WHAT
HAPPENED, WE STARTED HAVING
VERY, VERY GOOD DRUGS, AND
BEFORE I GO TO THE NEXT SLIDE
I'LL JUST POINT OUT THAT CHRONIC
HCV IN WEST VIRGINIA, AGAIN, IS
IN THE SOUTHERN PART OF THE
STATE.
NEXT SLIDE.
SO, WE HAD DRUGS THAT COULD CURE
CHRONIC HEPATITIS C IN 8 TO 12
WEEKS.
I MEAN, IT WAS REALLY AN
UNBELIEVABLE ADVANCE,
THERAPEUTIC ADVANCE.
THE PROBLEM WAS, THERE WERE TWO
PROBLEMS.
NUMBER ONE, PBN PRACTITIONERS
SAID YOU GOT TO HELP US WITH
THIS, WE'RE BEING INUNDATED WITH
HEPATITISC, THERE ARE DRUGS, WE
DON'T KNOW HOW TO USE THEM.
CRAIG ROBINSON AND AMBER CRIST
SAID YOU'RE FREE NEXT WEEK,
WE'RE GOING TO ALBUQUERQUE, YOU
GOT A PLANE TICKET TO LOOK IT
THE NEW MEXICO, UNIVERSITY OF
NEW MEXICO ECHO PROGRAM
EXTENSION FOR HEALTH CARE
OUTCOMES.
WHICH HAD A SUCCESSFUL PROGRAM
TREATING HEPATITIS C, LONG
BEFORE REALLY THERE WERE GOOD
DIRECTLY ACTING AGENTS.
WE WENT.
WE IMPLEMENTED THE ECHO PROGRAM
WHICH OCCURS EVERY COUPLE OF
WEEKS.
THERE ARE TWO CASE
PRESENTATIONS.
AND THEN THERE'S ABOUT A
15-MINUTE DIDACTIC.
THE STATE OF WEST VIRGINIA HAD A
REQUIREMENT WV MEDICAID WITH
ONLY COVER INDIVIDUALS WITH
DIRECTLY ACTING AGENTS SO
EFFECTIVE IF THEY SAW AN I.D. OR
G.I. SPECIALIST.
OFTEN THE WAIT WAS 6 TO 9
MONTHS, IT WAS HOURS OF TRAVEL
FOR SOME FOLKS.
WE WENT TO WEST VIRGINIA
MEDICAID AND SAID, LISTEN, COULD
YOU COUNT PRESENTATION AT ECHO
AS THAT SUBSPECIALTY
CONSULTATION?
PRIMARY CARE PHYSICIANS WERE
CLEAR.
I MEAN, THEY HAD NEW OF KNEW HOW
TO TREAT AND USE THOSE AND WV
MEDICAID, GOT RID OF ADVANCED
FIBROSIS TREATMENT, LOOKING AT
ECONOMIC ANALYSIS, NUMBER OF
PEOPLE TREATED.
NEXT SLIDE.
THAT WASN'T THE END OF THE ECHO
PROGRAM.
TODAY WE HAVE ALL OF THESE
PROJECTS THAT WERE -- A LOT OF
PBRN AND OTHERS SAID WE NEED
THIS.
WE'RE IN MOST OF THE WEST
VIRGINIA COUNTIES SHOWN IN BLUE.
WE ALSO -- WEST VIRGINIA ECHO IS
IN 20 ADDITIONAL STATES.
THERE ARE CURRENTLY NEGOTIATIONS
WITH WV MEDICAID TO SUPPORT THE
ECHO PROGRAM.
NEXT SLIDE.
THERE ARE TWO CURRENT HIV
OUTBREAKS, ONE IN THE COUNTY
WITH THE BLUE PIN, ONE IN THE
COUNTY WITH THE RED PIN.
YOU'LL SEE A GRAY PIN BY
WHEELING, IT HASN'T BEEN
OFFICIALLY CALLED.
THESE OUTBREAKS ARE 95% FOLKS
THAT USE INTRAVENOUS DRUGS.
A THIRD OF THE HIV IS DIAGNOSED
IN THE HOSPITAL, THIS WASN'T
SOMETHING THAT GOT HIV
YESTERDAY.
THESE ARE INDIVIDUALS WHO ARE
NOW PRESENTING AFTER HAVING HIV
FOR YEARS WITH COMPLICATIONS.
MORE THAN 40% ARE WOMEN.
AND RECENTLY, THE LEGISLATURE IN
THE STATE OF WEST VIRGINIA MADE
IT DIVERSITY RESULT,
REQUIREMENTS FOR SYRINGE SERVICE
PROGRAMS, MANY HAVE CLOSED, A
GOOD SYRINGE SERVICE PROGRAM IN
CABELL COUNTY HEALTH DEPARTMENT,
IT'S IN THE NEWS THEY MAY HAVE
TO CLOSE.
DO REMEMBER THE OUTBREAK OF HIV
IN SOUTHERN INDIANA, SCOTT
COUNTY, THAT EPIDEMIC WAS ONLY
BROUGHT UNDER CONTROL WHEN THE
GOVERNOR PENCE AT THAT TIME
AGREED TO HAVE SYRINGE EXCHANGE.
AND THERE HAD BEEN MODELING, IF
THEY HAD EFFECTIVE SYRINGE
EXCHANGE THERE WHO HAVE BEEN
MANY FEWER CASES.
THE OTHER THING I WOULD SAY
GOING BACK TO CLINICAL TRIALS,
EXACTLY ZERO, ZERO CLINICAL
TRIALS IN WEST VIRGINIA ON HIV
PREVENTION.
WHEN WE LOOK AT WHAT'S NEEDED,
YOU HAVE TO PUT CLINICAL TRIALS
WHERE YOU'RE HAVING OUTBREAKS.
YOU'RE NOT GOING TO ELIMINATE
HIV BY DOING ALL YOUR STUDIES IN
NEW YORK CITY AND SAN FRANCISCO.
NEXT SLIDE.
THIS IS NO SURPRISE, OF COURSE.
WEST VIRGINIA USED TO HAVE A
VERY LOW HIV DIAGNOSIS RATE IS
INCREASED.
YOU'LL SEE IT TAILS OFF AT 2019.
THAT ISN'T TAILED OFF.
IT'S BECAUSE WITH COVID THERE'S
NOT BEEN MUCH TESTING.
I AM SURE THAT WE'RE NOW ABOVE
THE U.S. AVERAGE.
NEXT SLIDE.
ANOTHER STUDY THAT WAS FUNDED A
COUPLE YEARS AGO BY GMS LOOKED
AT PERCEPTIONS OF RISK AMONG
WOMEN.
REMEMBER, WOMEN CONSTITUTED MORE
THAN 40% OF THE NEW HIV CASES.
IT WAS MIXED METHODS.
ACTUALLY, MY HBTN STUDY, NIAID
STUDY THAT I WAS PROTOCOL CHAIR,
IT LOOKED AT 2,000 URBAN WOMEN,
A DECADE AGO, LOOKING AT HIV
RISK WITH AUDIO ASSISTED
COMPUTER SELF-INTERVIEW, FOLKS
HAD HEADPHONES, YOU DIDN'T HAVE
TO BE LITERATE TO ANSWER
QUESTIONS, WE DID SEMI
STRUCTURED INTERVIEWS, ENROLLED,
NEXT SLIDE, 88 WOMEN.
I DID 10 INTERVIEWS MYSELF.
THEY WERE JUST HEART WRENCHING.
THOUGH MOST OF THE INDIVIDUALS,
YOU CAN SEE DEMOGRAPHIC SHOWN
THERE, MOST HAD BEEN TESTED AT
LEAST ONCE.
WHAT EMERGED IN THE QUALITATIVE
WERE THEMES, THREE OF THE FOUR
THEMES WE HAD SEEN IN THE 064
STUDY OF URBAN WOMEN, ISOLATION,
VIOLENCE AGAINST WOMEN, REALLY
COMMUNITY STIGMA.
I WOULD SAY THE VIOLENCE AGAINST
WOMEN, IT WAS HARD TO FIT AND
HEAR SOME OF THESE WOMEN'S
STORIES.
IT WAS UNBELIEVABLE.
MY VIEW WAS I THINK SOME
VIOLENCE IN RURAL AREAS MAY BE
MORE INTENSE FOR A NUMBER OF
REASONS.
WHAT I NEVER HEARD IN NEWARK,
AND NEWARK'S HIV EPIDEMIC, FOR
THOSE THAT DON'T I RAN AN HIV
PROGRAM, BIG HIV PROGRAM IN
NEWARK FOR TEN YEARS, THAT --
AND THAT EPIDEMIC WAS PREDICATED
ON INTRAVENOUS DRUG USE, HIGHEST
PROPORTION OF WOMEN BECAUSE THEY
DIDN'T KNOW THEIR PARTNERS WERE
SHOOTING DRUGS AND WERE
INFECTED.
I NEVER HEARD INTERGENERATIONAL
DRUG USE.
MULTIPLE WOMEN SAID I WAS FIRST
SHOT UP FOR MY 7th BIRTHDAY,
SHOT UP AT 9 BECAUSE THEY WANTED
ME TO SHUT UP.
I MEAN, THIS IS SOMETHING THAT I
THINK HAS NOT BEEN WRITTEN
ABOUT, AND IS REALLY SOMETHING
THAT NEEDS ATTENTION.
JUST GOING TO THE RIGHT SIDE OF
THE SLIDE HERE YOU SEE THAT 80%
OF WOMEN REPORTED CURRENT OR
PAST INTRAVENOUS DRUG USE, A
QUARTER HAD A SEXUAL PARTNER WHO
ENGAGED IN DRUG USE, 40% HAD A
PARTNER WHO HAD BEEN IN PRISON,
YET, YOU KNOW, 85% OF THE WOMEN
DID NOT THINK THEY WERE AT HIV
RISK.
SO I THINK THAT THIS REALLY IS
CRITICAL EVIDENCE THAT WE REALLY
NEED EDUCATION PREVENTION
PROGRAMS OR THIS THING IS IN
WEST VIRGINIA IS GOING TO BE
EXPLOSIVE.
I'LL FINISH WITH INNOVATIVE
TREATMENT.
THE PROBLEM CURRENTLY WITH
TREATMENT OF OUD, OPIOID USE
DISORDER, SUBSTANCE USE
DISORDER, CLICK ONCE MORE, IS
THAT THE RATE OF SUCCESS FOR
THESE TREATMENTS IS LESS THAN
50%.
POLY SUBSTANCE USE IS COMMON.
AND MOST NON-OPIOID SUBSTANCES
DO NOT HAVE A MEDICATION
TREATMENT AVAILABLE.
THEY RELY MOSTLY ON BEHAVIORAL
TREATMENTS, THE EXCEPTION OF
COURSE IS OPIOID USE DISORDER
WHICH REALLY HAS MEDICATION
TREATMENT METHADONE, SUBOXONE
AND SO FORTH BUT CLEARLY THIS IS
AN UNMET NEED.
CLICK THROUGH TILL YOU GET
THROUGH.
SO, YOU HAVE TO UNDERSTAND WHY
WE DID THIS.
ADDICTION'S A BRAIN DISORDER
WITH MULTIPLE AREAS INVOLVED.
ACUTE OPIOID USE INCREASES
DOPAMINE IN THE NUCLEUS
ACCUMBENS, AT THE CENTER OF THE
REWARD CIRCUITRY.
YOU FEEL GOOD WHEN YOU HAVE A
LOT OF DOPAMINE.
YOU REALLY WANT MORE.
OVER TIME, THE DOPAMINE
DECREASES, IN THE NUCLEUS
ACCUMBENS LEADING TO INCREASE
THE CRAVING IN EFFORT TO
INCREASE THE DOPAMINE.
DECREASED DOPAMINE REDUCES
PREFRONTAL CORTEX ACTIVITY
LEADING TO POOR EXECUTIVE
FUNCTION AND DECISION MAKING AND
THIS IMBALANCE WORSENS OVER
TIME.
NEXT SLIDE.
DEEP BRAIN STIMULATION HAS BEEN
DONE FOR A NUMBER OF THINGS.
HE SAID WE SHOULD WRITE THIS
GRANT.
CTR, SOMEBODY HAS A GREAT IDEA,
WE WERE IN THE WAR ROOM, WROTE
THIS GRANT.
WE WERE FUNDED BY NIDA FOR
FOR-PATIENT FEASIBILITY STUDY,
INCLUSION CRITERIA SHOWN THERE,
MOST IMPORTANTLY YOU HAD TO HAVE
FAILED MULTIPLE TREATMENT
ATTEMPTS FOR OPIOID USE
DISORDER, AND YOU ALSO, YOU
KNOW, HAD TO HAVE MULTIPLE
DOCUMENTED OVERDOSE.
THESE WERE NOT FOLKS THAT JUST
HAD ONE TREATMENT ROUND AND HAD
FAILED IT.
NEXT SLIDE.
THESE ARE OUR BASELINE
CHARACTERISTICS, JUST TO SAY
THAT LOOK AT THE NUMBER OF
OVERDOSES, 5 TO 11, AND THESE
WERE NOT FOLKS IN TREATMENT, ALL
OF THESE FOLKS HAD USED WITHIN
THE LAST WEEK BEFORE ENTERING
THE TRIAL.
NEXT SLIDE.
THIS IS THE PROCEDURE JUST TO
SHOW YOU IF THE NEUROSURGEON
WERE HERE HE WOULD GO ON FOR
HALF AN HOUR, BUT THE NUCLEUS
ACCUMBENS IS DEEP.
THEY PUT STIMULATORS IN.
NEXT SLIDE.
AND THEN THERE IS A POWER PACK
IN THE CHEST.
NEXT.
AND JUST YOU CAN CLICK THROUGH,
ARROWS WILL COME UP.
THERE IS A CRAVING SCALE WHERE
THEY SHOW VARIOUS SORT OF
PICTURES AND THEN THE PATIENT
WILL SHOW ON THE SCALE WHERE
THEY FIT.
AND YOU CAN SEEP GOING.
NEXT SLIDE.
AND ACTUALLY, INTRAOPERATIVELY,
CLICK ONCE MORE, THE PATIENT IS
AWAKE, AND RESPONDS TO THESE
TRIGGERS, SUCH THAT THEY CAN
SEE, YOU KNOW, THAT THEY HAVE
NOT ONLY BY RADIOGRAPHY BUT THEY
HAVE THE STIMULATOR IN THE
CORRECT PLACE.
AND YOU CAN SEE BASELINE VERSUS
INTRAOPERATIVE IT COMES DOWN.
NEXT SLIDE.
THESE ARE THE RESULTS.
PATIENT NUMBER 1 HAD HAD
MULTIPLE TREATMENT FAILURES,
OPIOID USE DISORDER FOR DECADES,
AND HAS NOW BEEN ABSTINATE.
WE DO LIQUID CHROMATOGRAPHY TO
GET THE SUBSTANCES.
NUMBER 2 WAS IN AND OUT OF
PRISON, KEPT USING, A MUTUAL
AGREEMENT WITH PARTICIPANT AND
TEAM THAT HIS STIMULATOR WAS
ACTUALLY REMOVED.
PATIENT NUMBER 3 AGAIN DID
GREAT.
REMEMBER, THESE ARE FOLKS THAT
HAD MULTIPLE OVERDOSES, MULTIPLE
TREATMENT FAILURES, NOW
ABSTINATE NOW OUT TO MORE THAN
500 DAYS, PATIENT 1 AND
PARTICIPANT 3 ARE EMPLOYED,
INTERESTINGLY PARTICIPANT 4
INITIALLY HAD ISOLATED RELAPSES,
BUT AS TIME HAS GONE ON HE IS
NOW MONTHS WITHOUT ANY RELAPSES,
AND CURRENTLY HAS FOUND
EMPLOYMENT SUGGESTING PERHAPS AS
THE CIRCUITRY IS NORMALIZED, YOU
HAVE MORE DOPAMINE TO THE
PREFRONTAL CORTEX, BETTER
EXECUTIVE CONTROL.
ACTUALLY, WE HAVE PET SCANS THAT
ACTUALLY LABEL THE DOPAMINE AND
YOU CAN SEE INCREASE IN THE
PREFRONTAL.
NEXT SLIDE.
SO, IN CONCLUSION, YOU KNOW,
IDeA CTRs ARE CATALYST FOR
RESEARCH FOCUSING ON RURAL
HEALTH AND UNDERSERVED ISSUES.
WEST VIRGINIA IS THE CATALYST.
IDEA CTRs HAVE WORKED IN
EXEMPLARY FASHION TOGETHER ON
BIG DATA AND NOW CLINICAL
TRIALS.
AND THAT IS I THINK FERTILE
GROUND FOR FUTURE INCREASES.
AND I THINK ENGAGEMENT, FINALLY
THIS IS MOST IMPORTANT, RURAL
POPULATION IN RESEARCH IS
CRITICALLY IMPORTANT TO
FACILITATING BELIEF AND TRUST IN
SCIENCE.
I GREW UP AT AN APPALACHIAN
RIVER TOWN, DIFFERENT TIME.
YOU HAD, YOU KNOW, LIFE MAGAZINE
WITH ALL THE PICTURES, YOU CAN
SEE THE WORLD TODAY.
NONE OF THAT EXISTS.
THERE'S JUST THE INTERNET WITH A
LOT OF MISINFORMATION, AND
EVERYBODY IN THEIR OWN ECHO
CHAMBER.
I THINK UNLESS, YOU KNOW, WE
ACTIVELY ENGAGE AND MAKE TRIALS
AVAILABLE, WHY WOULD FOLKS
BELIEVE, YOU KNOW, SOMETHING
FROM MORGANTOWN OR WASHINGTON,
D.C.?
I MEAN, IT'S REALLY IMPORTANT TO
HAVE SUBSTANTIVE INPUT BY THESE
COMMUNITIES AND THE CTRs CAN
REALLY PROVIDE FOR THAT.
THEN I WANT TO CONCLUDE WITH
ACKNOWLEDGMENTS, NEXT SLIDE
SHOWS THE TEAM WITH THE DEEP
BRAIN RESEARCH, DEEP BRAIN
STIMULATION.
IT'S A CAST OF A LOT OF PEOPLE.
FINALLY, OUR NEXT SLIDE, OUR
CTSI, IT'S ABOUT A THIRD OF THE
GROUP NOW.
WE HAVE 65 FOLKS.
A LOT OF FOLKS INVOLVED IN ALL
THESE PROJECTS.
PARTICULARLY I'D LIKE TO THANK
DR. LEY, BRUNE L AND MORELL.
NONE OF THIS WOULD HAVE HAPPENED
WITHOUT THEM.
WE HAVE A NUMBER OF QUESTIONS
STARTING WITH ONE, THE PERSON IS
CURIOUS ABOUT THE MAP SHOWING
SARS-COV-2 VARIANT SPREAD.
YOU NOTED MANY STARTED NEAR
MORGANTOWN.
DO YOU HAVE A HYPOTHESIS ABOUT
THIS BEING RELATED TO THE
UNIVERSITY OR MOBILE POPULATION
ASSOCIATED WITH UNIVERSITY AND
SPECULATE A CAUSAL LINK WITH
SPREAD THROUGHOUT THE STATE?
>> SO, WE'RE LOOKING AT THIS,
BUT MORGANTOWN IS AN HOUR DUE
SOUTH OF PITTSBURGH AND
UNIVERSITIES, WE'VE ALL BEEN
THERE.
HAVE YOU PEOPLE IN AND OUT FROM
ALL OVER THE WORLD.
SO, YES, THAT'S TRUE.
BUT THE OTHER THING THAT I THINK
IS REALLY IMPORTANT IS WHAT
APPEARS TO BE THE SPREAD DOWN
THE MAJOR HIGHWAYS.
AND, YOU KNOW, THE SARS-COV-2
IS, YOU KNOW, AEROSOL AND
RESPIRATORY DROPLETS.
EARLY ON IN THE AIDS EPIDEMIC,
ABE BERGAZI WROTE ABOUT THE
SPREAD ALONG THE INTERSTATE WITH
TRUCKERS, NOT A NEW IDEA.
BUT I THINK, YOU KNOW, YOU CAN'T
JUST SAY IT'S ONLY THIS WAY.
OF COURSE IT ISN'T.
YOU'VE GOT THE EASTERN PANHANDLE
THAT DIDN'T APPEAR TO AFFECT
MUCH OF -- THEY GOT IT FROM YOU
GUYS IN D.C. AND WERE GIVING IT
BACK OVER THERE.
AND, YOU KNOW, YOU REALLY HAD
THIS DELTA THAT REALLY CAME IN
WITH THE INFLUX OF TRAVEL.
CLEARLY IT'S TRAVEL.
IT'S PEOPLE GOING FROM OUTSIDE.
I THINK YOU HAVE MORE OF THAT IN
MORGANTOWN THAN ANYPLACE ELSE.
>> RIGHT.
MAKES SENSE.
A QUESTION ALSO ABOUT THE
ANTICOAGULANT TREATMENT YOU
SHOWED, OR THE EFFECTS.
WHY WAS THE ANTICOAGULANT
TREATMENT -- HAD A HIGH NEGATIVE
EFFECT ALONE BUT POSITIVE EFFECT
IN ALMOST ALL THE COMBINATION
TREATMENTS WITH DIFFERENT
THERAPEUTICS?
>> YEAH, THAT'S A GREAT
QUESTION.
I THINK THAT, YOU KNOW, AGAIN AS
I SAID, IT'S INTRIGUING WHY
ANTICOAGULANTS ALONE WERE
NEGATIVE IMPACT.
I THINK THAT REALLY HAD TO DO
WITH PEOPLE WHO HAD SEVERE
THROMBOEMBOLIC COMPLICATIONS.
I THINK THAT WAS A GROUP, OR A
GROUP WHERE PEOPLE DIDN'T WANT
TO GIVE THEM STEROIDS.
THE ISSUE WITH THE COMBINATIONS,
THAT'S THE INTERESTING THING
ABOUT THIS PAPER, COMBINATIONS
APPEAR TO DO BETTER E -- AND
STEROIDS WAS THE ONLY SINGLE ONE
YOU HAVE, THE ONLY THING FROM
SHAP VALUES, WHICH FEATURES WERE
MOST IMPACTFUL, MUCH DATA COMES
EARLY ON IN THE PANDEMIC BEFORE
WE HAD BETTER SORTS OF
ANTI-VIRALS.
AND I THINK THAT IT'S GOING TO
BE INTERESTING TO RELAPSE REPEAT
IT.
THE OTHER THING I SHOULD SAY IS
WE REALLY TRIED IN OUR, YOU
KNOW, SORT OF DATASETS TO
EXCLUDE THE ANTI-COAGULATION.
EVERYBODY IN THE HOSPITAL IS ON
PREVENTIVE DVT THERAPY, THAT WAS
EXCLUDED.
WE WERE LOOKING FOR PEOPLE ON
THERAPEUTIC ANTI-COAGULATION,
SUGGESTING, YOU KNOW, AT LEAST
EARLY ON THOSE WERE PROBABLY
PEOPLE WHO WERE MORE SICK.
>> BEFORE WE GO TO THE LAST
QUESTION I'VE BEEN ASKED TO SAY
THE CME NUMBER AGAIN.
IF YOU WANT THE CME NUMBER,
44433.
SO, LAST QUESTION FOR YOU,
SALLY.
MUCH MORE GENERAL ONE.
WHAT'S THE BIGGEST BARRIER TO
GETTING RURAL PATIENTS ENGAGED
IN CLINICAL TRIALS, IN YOUR
EXPERIENCE?
>> WELL, THAT'S A GREAT
QUESTION.
I WOULDN'T, YOU KNOW, SORT OF
PRESUME TO HAVE THE ANSWER BUT I
WILL SAY THAT WE DID FOCUS
GROUPS, AND THIS WAS RIGHT
BEFORE COVID, AROUND THAT ISSUE.
WE REALLY WANTED TO EXPAND
CLINICAL TRIALS.
AND THE NUMBER ONE REASON THAT
RURAL FOLKS IN THOSE FOCUS
GROUPS SAID THEY HAD NOT BEEN IN
CLINICAL TRIALS, NOBODY ASKED
THEM, THEY DIDN'T KNOW IT WAS
AVAILABLE.
AND SO I THINK THE MOST
IMPORTANT BARRIER IS TO MAKE
THESE TRIALS AVAILABLE TO FOLKS.
AND, YOU KNOW, YOU'RE NOT GOING
TO TAKE A FIRST-IN-HUMAN AND
ENROLL SOMEBODY DOWN IN McDOW
COUNTY, SOUTHERNWEST VIRGINIA.
MANY ARE BECOMING COMMON, PBRN
PARTICIPATED IN AN ACTIV TRIAL
WITH COAGULATION, ENROLLED AT
THE SITE AND THEN ACTUALLY
EVERYTHING ELSE WAS REMOTE.
THEY WERE AUTOMATICALLY SENT THE
DRUG AND SO FORTH.
I THINK WE'RE GETTING, YOU KNOW,
MUCH MORE CREATIVE ABOUT HOW TO
INCLUDE THESE PEOPLE.
I THINK, YOU KNOW, WHAT I SAID
AT THE END IS WHAT'S MOST
IMPORTANT.
ALL THE MOST ELEGANT SCIENCE IN
THE WORLD IS FAR LESS VALUABLE
IF PEOPLE DON'T BELIEVE IT.
I THINK UNLESS WE ENGAGE PEOPLE
AND BRING CLINICAL TRIALS AND
REALLY TAKE THEIR INPUT TO
HEART, I THINK THAT OUR SCIENCE
IS GOING TO BE MUCH LESS
IMPACTFUL THAN IT OTHERWISE
WOULD.
>> I THINK THAT'S AN EXTREMELY
GOOD MESSAGE AND A GOOD WAY TO
END THIS GREAT TALK.
THANK YOU SO MUCH, SALLY.
WE APPRECIATE ALL THE WORK YOU
AND YOUR COLLEAGUES HAVE DONE.
AND APPRECIATE YOU FOR GIVING
THIS TALK FOR US.
THANK YOU VERY MUCH.
>> THANK YOU.