Panel: Improving Healthcare Research Through Collaboration

May 9th, 2018

11:30 AM – 12:30 PM

ASC 118

RonaldPirrallo,M.D.ViceChairforAcademics

DepartmentofEmergencyMedicineGreenvilleHealthSystem

ResearchTargetMap

HumanResponse

SystemAnalysis

ClinicalEffectiveness

Strategic Development of a Research Experience Enrichment Program (REEP) in the Department of Emergency Medicine

Dotan Shvorin PhD, Ronald Pirrallo MD, MHSA, Kevin Taaffe PhD, Phillip Moschella MD, PhD

ObjectiveTo establish a GHS-CU collaboration that

generates health care inquiries, aimed to improve

patient care processes by applying engineering

methods, within the GHS Department of

Emergency Medicine.

BackgroundThe Creative Inquiry (CI) program matches

motivated undergraduate and graduate students

with CU Faculty to facilitate imaginative engaged

learning and cross-disciplinary interactions to

produce the next generation of scholars.

HypothesisCan the CU CI program be adapted to the GHS

health care environment to advance GHS

scholarship and workforce development?

MethodsUnder the leadership of an embedded CU scholar, 6 teams of CI students were

matched with GHS EM Clinical Faculty and EM Residents to investigate topics

ranging from CPR training effectiveness to quantifying physician distractions to clinician

decision making under fatigue to describing clinician physiologic biomarker variability

during a shift to understanding the effect of consultant use on ED operations to TB

screening modelling.

Outcomes6 teams incorporating 12 EM GHS Faculty, 6 EM

residents, 18 Undergraduates and 5 graduate

students formed the Research Experience Enrichment Program (REEP) to answer 6

research questions in this academic year. The 6

teams generated 6 confirmed abstract conference

presentations that secured a CU internal award of $6k for dissemination.

ConclusionThe REEP appears to have successful built upon

the CU CI framework to produce promising

scholarly work and expose nearly 2 dozen CU students to the health care environment this

year. Future work will evaluate if these teams

generate peer reviewed manuscripts and track

how many CU REEP participants pursue careers

in health care.

Emergency Medicine Research Target MapMotivation Streamline Research Project: Yearly Cycle of Scholarly Activities

AlainLitwin,M.D.ViceChairforAcademics

DepartmentofInternalMedicineGreenvilleHealthSystem

Department of MedicineResearch Efforts

May 9, 2018Alain Litwin, MD, MPH

Vice Chair of Academics and ResearchDepartment of Medicine

Medicine Research Areas

ClinicalTrials OpentoEnrollment GHSEnrolled

Total Enrolled/ Goal

PIONEER-HF - PhaseIIIB/IVstudyofEntresto vs.enalapril onchangesinNT-proBNP instabilizedinpts withacutedecompensatedHF,EF<40%

9 642/882

Evolve ShortDAPT

- Assess safetyof3monthDAPTinptsw/highbleedingriskwhohadPCIwithSynergystent

22(1ScreenFailure)

1,457/2,000

TAILOR-PCI - Randomizedpost-PCItoprospectiveordelayedgenotypingtodeterminesensitivitytoplavix

50 4,450/5,270

GALACTIC-HF - PhaseIIIstudyofOmecamtiv Mecarbil inptswithchronicHFandreducedEF

- Eligibility:HFadmissionwithinthelastyearandEF< 35%

4(1ScreenFailure)

1,865/8,000

MINT(MyocardialIschemiaandInfusion)

AMIwithhemoglobin<10g/dL randomizedto1)LiberalTransfusionStrategy– transfuse

whenhemoglobin<102)RestrictiveTransfusionStrategy– transfuse

whenhemoglobin7-8

0 208/3500

Cardiovascular ResearchEnrolling Trials

Cardiovascular Research

InvestigatorInitiatedStudies Enrollment

AFib RotorMapping

Pilotstudyof compassmappingduringablationtoidentifyAFibrotors

26

5Trials inFollow-up

• ABSORBIII&IV(Abbott)• PROMUSRegistry(BostonSci)• CABANAAFib trial(DCRI/MayoClinic)

• Bioflow-VDES(Biotronik)• CardioMems PAS(St.Jude)

Ongoing Trials

Memory Health: Caring for Self, Caring for Others

Investigating the effects of the stress of caring for loved ones with Alzheimer’s Disease on caregivers, and developing solutions to support caregivers

Initially:•Duke Endowment grant•July 2014 – July 2017•$990,470

New Funding:•Administration for Community Living grant•September 2015 – September 2018•$995,890

Partnering to Transform Health Care

• NCORP: Adults and PediatricsØ 342 Clinical Trials (330 adult, 12 pediatric)

o Treatmento Preventiono Cancer Care Delivery

• Institute for Translational Oncology Research (ITOR)Ø Phase I Clinical Research Unit (CRU)Ø BiorepositoryØ Clinical Genomics CenterØ Innovation Zone

• Center for Integrative Oncology and Survivorship (CIOS)Ø Integrative Therapies

GHS Cancer Research

11

ITOR Biorepository Services• 2900 + unique patients • > 20,000 aliquots – cancer center

Ø fresh snap frozenØ live cell cryopreservationØ formalin-fixed paraffin embeddedØ blood (whole, plasma, serum)

• Genomic annotation with 50 gene hot spot panel• Legal Framework in place

• allows sharing of tissue and clinical annotation in research projects

• >20,000 aliquots – other DOM investigators

ITOR Innovation Zone

InnovationZone

NUBAD LLCNUCLEIC ACID BASED DRUGS

Center for Cancer Prevention and Wellness

14

CenterforCancerPreventionand

WellnessRiskStratification

NP-MDEvaluation/ManagementNavigationRegistry

Endocrine

GUProstate

Chemoprevention

HighRiskSurveillance

BreastPrevention

Multi-modality LungLowDose

CTScreening

Head/NeckScreeningGYN

EndometrialOvarian

BestChanceClinics

Screening

SkinMole

MappingScreening

GIColon&GEHighRiskLiver

Screening

Hereditary

Cancer

Prevention

Clinic

Hypothesis: • Abnormal RNA expression (nc RNA’s) precedes

protein (Biomarker) expression • Change in protein expression triggers clinical

expression of cancerGoal: • Establish predictive libraries of nc RNA that

precede clinical diagnosis of cancer and precede threat of host death of cancer

15

Solution:• Create Biorepository effort within CCPW to enroll tens of thousands of

our population with yearly blood banking to create hundreds of thousands of samples for ultimate transcriptionomic interpretation of cancer evolution.

• Dedicated enhanced effort to Biobank high risk (BRCA, Hep B, MDS) to characterize the pre-clinical molecular events, the associated environmental triggers and potential portals of intervention for achieving pre-clinical “Molecular Arrest” and even “Molecular Reversal” of the process.

• “Molecular Arrest” and even “Molecular Reversal” of oncogenic progression could be Environmental/Lifestyle alteration of nc RNA expansion in targeted therapy for neutralization of alteration nc RNA portfolio.

16

Variablesincluded•Ageatonset•Diseaseduration•HY•Subscores fromMDS-UPDRSpartn3and2•Subscores derivedjustwithpart3•MDS-UPDRSpart2– totalscore•MDS-UPDRSpart1– isolatedquestions

Variablesincluded•Ageatonset•Diseaseduration•HY•Subscores fromMDS-UPDRSpartn3and2•Subscores derivedjustwithpart3•MDS-UPDRSpart2– totalscore•MDS-UPDRSpart1– isolatedquestions

TPAoutcome

NIHSSextended

ARCADIA

PACESETTER MaRISS

ARAMIS

RESPECTESUS Fullerton

TARGET TIA

TimetoTPAanalysis

RESEARCH PIPELINESSTROKE CENTER

Startupactivities

EnrollmentPhase

Closeoutactivities

Waitingapproval

Observationalstudies

PhaseIIIrandomized

devices

INVESTIGATORINITIATED

SPONSORINITIATED

GRANT

Parkinson’s Disease Subtypes

18

Wearable Sensors QuantifyParkinson’s Disease Symptoms

19

Accelerating the Revolution in Population Health(care)

Healthcare Professional Performance Satisfaction

Patient Reported

Outcomes & Engagement

Clinical Outcomes &

Costs

Community Behavior Health & Environ

Data

Step 1: Capture clinical & population data

Data (360o View& Learning)• Clinical processes & outcomes• Patient-reported outcomes• Behavior, Socioeconomic,

Environment, Geospatial• Cost (cost effectiveness)

Step 2:Obtain 360o

view of data

Analysis• Prioritize community and

healthcare delivery system objectives and outcomes

• Identify key modifiable social and medical determinants impacting priority outcomes

Step 3:Analyze &

models data

Model & TranslateTranslate key determinants into effective action programs for :• Integrated health system• Patients• Communities

Step 4:Identify areas

to apply discoveries

Step 6:Analytics,

*research & services impact

* ≥75% of research is rapid learning health system (RLHS)

Implementation (interface with Clinics & Healthcare Systems / Communities to):• Conduct Pilot Interventions -----------------------------------------------------• Support Broad Implementation

Step 5: Implementati

on impact

CCI Pharmacological Treatment Algorithm

Regimen-13 pills; 3 meds

Regimen- 22 pills; 3 meds

Lisinopril 40 (Free)Benazepril /

Amlodipine 40 / 10 ($4/Mo)

Amlodipine 10($4/mo)

Indapamide 2.5 ($4/mo)

Indapamide 2.5($4/mo)

Total Cost:$8 / mo

Total Cost:$8 / mo

Regimen- 33 pills; 3 meds

Regimen – 4 2 pills; 4 meds

Losartan 100($4/mo)

Benazepril / Amlodipine 40 / 10

($4/mo)

Amlodipine 10($4/mo)

HCTZ / Spironolactone (25

/ 25, generic co-pay)

Indapamide 2.5($4/mo)

Total Cost:$12 / mo

Total Cost:Est. $8 - $20 / mo

Notes:1. Treatment algorithm should control 80%–90% of hypertensives to

<140/<902. If patients have compelling indications for specific BP med

classes, include them

64.6

75.3

50.0

55.0

60.0

65.0

70.0

75.0

80.0

85.0

90.0

Baseline Visit

Last MAP Visit

Perc

enta

ge

Impact of MAP / Target: BP on BP Control in Family Medicine: Phase 1/2 Results.

Phase 1 – Single Site

Phase 2 – 16 Sites

Hanlin RB, et al. J Clin Hypertension. 2018: in press (DOI: 10.1111/jch.13141).

Patients graduating from JUMP session with our residents and dietician

60.0

65.0

70.0

75.0

80.0

85.0

90.0

Week1-2

Week3-4

Week5-6

Week7-8

Week9-10

Week11-12

Adhe

rencerates,%

Studyweeks

DailyadherencetoDAAs

DOT

Group

Individual

1– 3– 5– 7– 9– 11–

Community-basedHCVtreatmentcolocatedwithOATprograms

PREVAIL: Intensive models of HCV care for people who inject drugs

Litwin AH,etal.EASL2017,Amsterdam.#PS-130

StudyArm ETR SVR12DOT 98.0%(50/51) 98.0%(50/51)Group 93.8%(48/51) 93.8% (48/51)Individual 96.1% (49/51) 90.2%(46/51)Total 96.0%(144/150) 94.0%(141/150)

Overalladherence:DOT(82.8%),Group(77.5%),Individual(74.4%)

NoSVRin9patients:3ingroup,5inindividualand1inDOT§ 3patientsdidnotachieve

undetectableHCVRNA§ 2patientsdiedduringtreatment§ 4patientswithHCVRNAnotdetected

atEOT

§ National study - 8 states, 16 sites§ Enrolling 750 Current PWID (injected within 3

months)§ 600 initiating HCV treatment with once daily

sofosbuvir/velpatasvir x 12 weeks

§ On-site HCV treatment at either:§ community health centers or § methadone treatment programs

§ Outcomes: Initiation, Adherence, Completion, SVR, Resistance, Reinfection (over 2 years)

§ Stakeholders: National advocacy & medical organizations (HRC, NVHR, AATOD, NATAP), government (CDC), clinicians, patients, industry

Real world DAA outcomes among PWIDHepatitis C Real Options

DAA-treatment naïveGt 1-6With and without HIV

Study Design

Randomization

v

mDOT

Patient Navigation Tx

Initiation

TxInitiatio

n

EOT

EOT SVR 12

SVR 12

ConsentBaseline Week 0

Up to 12 weeks to initiate treatment

Week 12

12 weeks sof/vel

Arm A: 1) OTP, N=150; 2) CHC, N=150Arm B: 1) OTP, N=150; 2) CHC, N=150

Week 24

Week 120Monthly follow up Quarterly follow up

Virtual DOT (vDOT) may be as effective as in-person modified DOT (mDOT) for people who use drugs

• 17patientstreatedwithSOF/LDV• 12/17(71%)usedillict drugswithin6

months;14/17(82%)haveinjecteddrugs

• 16/17(94%)achievedETR• vDOT adherence91%vs mDOT 83%

• .

AiCure

Some ways to bridge the cultural divide• Meet and Greet with Divisions of Medicine (e.g neurology, geriatrics,

and primary care).• Develop virtual networking spaces – for initial one-on-one and group

meetings and ongoing collaborations – new Clemson Building and/or Zoom

• Identify resources at CUSHR that are of interest to GHS Clinical Researchers

• Monthly Department of Medicine Research Seminar to be launched –will invite CUSHR investigators

• Web-based directory of researchers, mentors, and resources within HSC

AngelaSharkey,M.D.SeniorAssociateDeanofAcademicAffairs

USC School ofMedicine– Greenville

IntroductiontotheBiomedicalResearchersatUSCSOM-Greenville

May9,2018

AreasofExpertise• Microbiology:ESKAPEpathogens,mutagenesis,drugdiscovery,

growthanalysis,virulenceassays,QCofinstrumentationforprivatesector,antimicrobialpropertiesofproteins

• Cellbiology:cellculture,microscopy,flowcytometry• Biochemistry:proteindetection,proteinpurification,structure-

functionanalysis,enzymeassays,proteinsasbiomarkersofdisease,glycan-proteininteractions

• Molecularbiology:PCR,RT-PCR,molecularcloning,assessepigeneticmodifications,genemutationsindisease

• DevelopmentalBiology:IVF, embryoculture• ReproductivePhysiology:endocrinology(e.g.hormoneassays),

semenanalysis• Immunology:Flowcytometry,cellsorting,magneticcellseparation,

immunoassays,lymphocytefunctionassays

BMSFacultyResearchFocusAreasUSCSOMG– BiomedicalSciences Faculty FocusAreasSergioArce,M.D.,Ph.D. ImmunologyandpathogenesisofmultiplemyelomaandsarcoidosisAsaC.Black,Jr.,M.D. Pluripotentadultstemcellsandmultiplesclerosis

AnnaV.Blenda,Ph.D. Antimicrobialpropertiesofhumangalactinproteins;geneticspfSplitHandFootMalformation(SFHM)

ReneeJ.Chosed,Ph.D. Genetics/epigeneticsposttranslationalmodificationsanddiseaseprogression;molecularmechanismsofhumanembryodevelopment

StevenE.Fiester,Ph.D. Microbiology/infectiousdisease;virulenceofmultidrug-resistantbacterialpathogens

LaurenA.Gonzales,Ph.D. Vertebratepaleontology;evolutionofprimatebrain

RichardL.Goodwin,Ph.D. Mechanismsofcardiovasculardevelopmentandmalformation;cell-basedtherapies

RichardL.Hodinka,Ph.D.,F(AAM) Clinicalmicrobiology,infectiousdiseases;moleculardiagnostics,identificationandmonitoringofmicrobialpathogens

AnnBlairKennedy,LMT,BCTMB,DrPH Patientandstakeholderengagement;behavioralchangeinterventionsandintegrativemedicine

MohammedK.Khalil,DVM,M.S.Ed.,Ph.D. Medicaleducationandinnovativelearningstrategies;learningandinstructionaltechnology

ThomasI.Nathaniel,Ph.D. Neurology;stroke/telestrokeprogram;medicaleducationWilliamE.Roudebush,Ph.D. Embryology;preimplantationembryomorphometricsRebeccaRuss-Sellers,Ph.D. Healthservicesresearch;medicaleducation

JenniferTrilk,Ph.D. Exercisescience;ExerciseisMedicineGreenville;improvingpatienthealththroughexercise

MatthewTucker,Ph.D. Sleepandmemoryprocessing;medicaleducationShannaWilliams,Ph.D. Craniofacialstudy;medicaleducationWilliamWright,Ph.D. Diabeticretinopathy;medicaleducationassessmentpractices;curriculumdesign

SergioArce,MDPhDClinicalAssociateProfessor,Immunologyarce@greenvillemed.sc.edu

SergioArce,MDPhD- ImmunologySARCOIDOSIS MULTIPLEMYELOMA

3D-COLLAGENMATRICES

AnnaBlenda,PhDClinicalAssociateProfessor,GeneticsandBiochemistryablenda@greenvillemed.sc.edu

AnnaBlenda, PhDGeneticsCurrent/ActiveResearchProjects

1. Antimicrobialproperties ofhumangalectinproteins,specificallygalectin-9:- collaborationwithDr.Stowell,MDPhD,EmoryUSOM,- USCSOMGstudents:AnitaVenkatesh (M2)andMaryKMontesdeOca (M3)

2. Useofgalectin-9 proteinasabiomarker innon-invasivediagnosisofendometriosis:- collaborationwithDr.Lessey,MDPhD,GHS,- Aspire-Igrantproposalsubmitted,patientsamplesavailable,pilotstudyinitiated

3.FacultysponsorsupervisingcurrentM3studentRonnieFunkatEmorySOMinthesplithand-footmalformation geneticstudy:- collaborationwithDr.Schwartz,PhD,GreenwoodGeneticCenter

AnnaBlenda, PhDGeneticsResearchProjectsinDiscussionPhase

1. Roleofgalectin-9 inregulationofmultiplemyelomabiology:- collaborationwithDr.Arce,MDPhD,USCSOMG

2.Roleofgalectin-9 ingranulomaformation insarcoidosis:- collaborationwithDr.ArceandDr.Kornev,PhD,ClemsonU

3. Strokeresearch (roleofgalectins,metabolomicsprofiling,microbiomestudy):- collaborationwithDr.ThomasNathaniel,PhD,USCSOMG

ReneeJ.Chosed, PhDClinicalAssistantProfessor,BiochemistryandMolecularBiologychosed@greenvillemed.sc.edu

ReneeJ.Chosed, PhDBiochemistryCurrentProject1:ModelthehumanMixed-lineageleukemia(MLL)multi-proteincomplexinyeast(Saccharomycescerevisiae)• Molecularbiologytechniquestoaltertheyeastgenome• Analyzehistonemodificationstatusinthegeneticallyalteredyeast

strains• Assessprotein-proteininteractionswithintheMLLproteincomplex

CurrentProject2:Investigatethemolecularmechanismsresponsiblefor“self-correction”ofaneuploid humanembryospriortoimplantation• Measuregeneexpression(RT-PCR)inpre-implantationembryo

blastocoelfluid• Enzymeassaystodetectapoptosisinblastocoelfluid

StevenE.Fiester,PhDClinicalAssistantProfessor,Microbiologyfiester@greenvillemed.sc.edu

StevenE.Fiester, Ph.D.Microbiology• Research interests:

– Elucidation of virulence mechanisms in ESKAPE (Enterococcus faecium,Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii,Pseudomonas aeruginosa and Enterobacter species) pathogens allowingfor the development of therapeutics

– Collaborative investigation of atypical ESKAPE infections and ESKAPEpathogens with multidrug- and pandrug-resistances

• Key research accomplishments:– Recharacterized A. baumannii as

hemolytic– Demonstrated ability of A. baumannii to

utilize heme-b as an iron source• Demonstrated efficacy of galliumprotoporphyrin IX as an effectivetherapeutic against multidrug-resistantA. baumannii

RBCsaloneRBCswithA.baumannii

• CurrentResearch:– TargetingphospholipaseCofA.

baumannii fortherapeuticpurposes

– InvestigatinglocalizationofGa-PPIXinA.baumannii atArgonneNationalLabs

– CharacterizingA.baumannii isolatescausingnecrotizingfasciitis

• Privatecollaborations:– DevelopmentofaTrojanhorse

antibiotictotreatmultidrug-resistantK.pneumoniae

Contactinfo:sfiester@ghs.org

WilliamE.Roudebush, PhDClinicalAssociateProfessor,DevelopmentalBiology,ReproductivePhysiolopgyroudebus@greenvillemed.sc.edu

WilliamE.Roudebush,PhD• Developmentalbiology

– Fertilization• Enhancingsperm-egginteractions

– Roleofgrowthfactors(Platelet-activatingfactor;PAF)– Preimplantationembryodevelopment

• Roleofgrowthfactors(PAF)• Molecularmechanisms

– Self-correctionofaneuploidy

• Reproductivephysiology– Endocrinology

• Assaydevelopment&utilization– AMH;InhibinB;PAPP-A

– Therapeutics• EnhancingIUIoutcomes

– PAF

ToFindOutMoreAboutourBMSFacultyandTheirResearchInterests

• http://sc.edu/study/colleges_schools/medicine_greenville/faculty/faculty/index.php

– FilterbyDepartment• BiomedicalSciences

Guest Panelistsu Ronald Pirrallo, M.D., Vice Chair for Academics,

Department of Emergency MedicineGreenville Health System

u Alain Litwin, M.D., Vice Chair for Academics, Department of Internal MedicineGreenville Health System

u Angela Sharkey, M.D., Senior Associate Dean of Academic Affairs, USC School of Medicine – Greenville