Kaiser Foundation Hospitals

ADULT CHANGES IN THOUGHT (ACT) RESEARCH PROGRAM - THE ADULT CHANGES IN THOUGHT (ACT) U19 PROGRAM WILL EXPAND, MODERNIZE, AND IMPROVE ACT'S PROSPECTIVE COHORT STUDY TO ACHIEVE ADVANCES IN SCIENTIFIC UNDERSTANDING OF OLDER ADULTS IN GENERAL AND DEMENTIA AND ALZHEIMER'S DISEASE IN PARTICULAR. ACT IS SET IN A HEALTHCARE DELIVERY SYSTEM. THE STUDY TEAM IDENTIFIES INCIDENT CASES OF DEMENTIA AND ALZHEIMER'S DISEASE AND FOLLOWS CONSENTING PARTICIPANTS TO AUTOPSY. THE PROGRAM WILL TRANSFORM THE CURRENT ACT U01 TO A U19, WHICH ENVISIONS COMPLEX MULTI-COMPONENT PROGRAMS THAT WILL HAVE A POWERFUL INFLUENCE ON THE FIELD. THE PROGRAM'S OVERARCHING GOAL IS TO IDENTIFY RISK FACTORS ACROSS THE LIFE COURSE THAT PROVIDE POTENTIAL INTERVENTION TARGETS FOR PRESERVING COGNITION AND PREVENTING ALZHEIMER'S DISEASE AND RELATED DEMENTIAS (ADRD). THE OVERALL SPECIFIC AIMS ARE: AIM 1. EXPAND ACT COHORT ENROLLMENT AND MODERNIZE AND IMPROVE FOLLOW-UP WITH EMPHASIS ON INCREASING RACIAL/ETHNIC DIVERSITY AND DEEP PHENOTYPING OF LIFE COURSE RISK FACTORS, COGNITIVE AND PHYSICAL FUNCTIONING, AND OUTCOMES INCLUDING NEUROIMAGING AND NEUROPATHOLOGY BASED ADRD OUTCOMES. THE CORES WILL EXPAND COHORT ENROLLMENT FROM 2,000 TO 3,000. THE STUDY WILL INVEST IN SIX CORES: A, ADMINISTRATIVE; B, CLINICAL; C, LIFE COURSE; D, NEUROPATHOLOGY; E, NEUROIMAGING; F, DATA AND ANALYSIS. THESE CORES WILL WORK TOGETHER TO FURTHER ENHANCE THE VALUE OF ACT'S RESOURCES, ENABLING THE ACT STUDY TO CONTINUE TO BE THE FOUNDATION FOR AN EXTRAORDINARY ARRAY OF SCIENCE. TO DATE, ACT HAS ACHIEVED A COMPLETENESS OF FOLLOW-UP INDEX OF 94.5% AND HAS OBSERVED 56,140 PERSON-YEARS OF FOLLOW-UP. ACT HAS IDENTIFIED >1,300 INCIDENT DEMENTIA CASES AND >1,000 INCIDENT ALZHEIMER'S CASES. THE STUDY HAS COMPLETED >850 AUTOPSIES AND WILL SURPASS 1,100 AUTOPSIES THIS CYCLE. ADDITIONALLY, 1,077 ACT PARTICIPANTS HAD ONE MRI SCAN, AND 540 HAVE HAD =2, WITH FUNDING IN PLACE FOR HUNDREDS MORE. AIM 2. SUPPORT KEY PROJECTS STUDYING THE SPECTRUM OF HEALTHY FUNCTIONING TO ADRD IN OLDER ADULTS. THE THREE PROJECTS CENTER AROUND 24-HOUR CYCLE PHYSICAL ACTIVITY, SEDENTARY BEHAVIOR, AND SLEEP PATTERNS IN OLD AGE (PROJECT 1), THE IMPLICATIONS OF COGNITIVELY DEFINED ALZHEIMER'S DISEASE SUBGROUPS (PROJECT 2), AND MECHANISMS UNDERLYING NEURAL PROTECTION AND TOXICITY OF STRONG ANTICHOLINERGIC DRUGS AND ANTIHYPERTENSIVE DRUGS (PROJECT 3). AIM 3. EXPAND AND IMPROVE ACT'S DISSEMINATION OF EXCEPTIONAL RESOURCES TO THE RESEARCH COMMUNITY GUIDED BY NIA'S ADOPTED FAIR (FINDABLE, ACCESSIBLE, INTEROPERABLE, AND REPRODUCIBLE) PRINCIPLES. ACT HAS PROVEN TO BE AN EXCEPTIONAL RESOURCE TO THE RESEARCH COMMUNITY, PROVIDING DATA AND SPECIMENS TO RESEARCH COLLEAGUES LOCALLY, ACROSS THE COUNTRY, AND AROUND THE WORLD, AND PROVIDES MENTORSHIP TO JUNIOR INVESTIGATORS. WE WILL CONTINUE TO ENHANCE OUR DATA SHARING CAPABILITIES IN THIS U19 PROGRAM.

KAISER PERMANENTE NCI NATIONAL COMMUNITY ONCOLOGY RESEARCH PROGRAM NCORP

INTEGRATING ADDICTION RESEARCH IN HEALTH SYSTEMS: THE ADDICTION RESEARCH NETWORK

ALZHEIMER'S DISEASE PATIENT REGISTRY (ADPR)

EARLY LIFE EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS AND CHILD GROWTH, ADIPOSITY, AND NEURODEVELOPMENT

A RESOURCE FOR GENETIC EPIDEMIOLOGY RESEARCH IN ADULT HEALTH AND AGING

KAISER WASHINGTON VTEU SUPPLEMENT 20-0003

INFRASTRUCTURE FOR PATHWAYS, A PROSPECTIVE STUDY OF BREAST CANCER SURVIVORSHIP

NATIONAL DENTAL PRACTICE-BASED RESEARCH NETWORK: COORDINATING CENTER

CRN4: CANCER RESEARCH RESOURCES & COLLABORATION IN INTEGRATED HEALTH CARE SYSTEMS

EXOME SEQUENCING IN DIVERSE POPULATIONS IN COLORADO & OREGON

OPTIMIZING COLORECTAL CANCER SCREENING PRECISION AND OUTCOMES IN COMMUNITY-BASED POPULATIONS (PRECISE)

CENTER FOR RESEARCH TO OPTIMIZE PRECISION LUNG CANCER SCREENING IN DIVERSE POPULATIONS

STUDY OF THE CARE AND OUTCOMES OF RENAL INSUFFICIENCY

PRECONCEPTION AND PRENATAL HEALTH IMPACTING FACTORS AND CHILD HEALTH - CHILDHOOD OBESITY AND NEURODEVELOPMENTAL IMPAIRMENTS HAVE INCREASED IN RECENT DECADES AND ARE THE MOST PREVALENT CONDITIONS THREATENING CHILD’S HEALTH AND WELL-BEING. THE CONSEQUENCES OF THESE CONDITIONS SIGNIFY THE NEED TO IDENTIFY MODIFIABLE FACTORS TO TARGET FOR UPSTREAM PREVENTION. EMERGING EVIDENCE SUGGESTS THAT PRENATAL EXPOSURES TO PSYCHOLOGICAL DISTRESS, SUBSTANCE USE, AND LIFESTYLE FACTORS DURING CRITICAL WINDOWS OF FETAL DEVELOPMENT MAY OPERATE TO DEVELOPMENTALLY PROGRAM CHILDHOOD OBESITY AND NEURODEVELOPMENT (ND). HOWEVER, FEW STUDIES HAVE TAKEN A MULTIPLE-EXPOSURE APPROACH TO UNDERSTAND THE INDIVIDUAL AND JOINT EFFECTS OF THESE EXPOSURES. IN AIM 1 WE WILL EXAMINE THE ROLE OF IN UTERO EXPOSURE TO PSYCHOLOGICAL DISTRESS AND SUBSTANCE USE ON CHILD GROWTH, ADIPOSITY, OBESITY, AND ND AND THE EXTENT TO WHICH PRENATAL LIFESTYLE FACTORS AND NEIGHBORHOOD FACTORS MAY MITIGATE THESE ASSOCIATIONS. FURTHER, WHILE MATERNAL DIET AND PHYSICAL ACTIVITY IMPACT INFANT GROWTH AND ADIPOSITY, FEW STUDIES HAVE ASSESSED MECHANISTIC PATHWAYS AND LITTLE IS KNOWN ABOUT THEIR IMPACT ON ND. WE PROPOSE THE 24-HOUR MOVEMENT PROFILE AND METABOLOMICS AS OUR SPECIALIZED MEASURES OF LIFESTYLE, AND OBESITY AND ND AS OUR SPECIALIZED OUTCOMES. THE 24-HOUR MOVEMENT PROFILE INCORPORATES THE INTERDEPENDENT RELATIONSHIPS BETWEEN DEVICE-BASED MEASURES OF PHYSICAL ACTIVITY AND SLEEP DURING PREGNANCY TO BETTER INFORM INTERVENTIONS. METABOLOMICS CAN ELUCIDATE MECHANISTIC PATHWAYS AND WILL BE MEASURED REPEATEDLY ON THE SAMPLES COLLECTED ACCORDING TO THE ECHO PROTOCOL (PRENATAL BLOOD, CORD BLOOD, POSTNATAL CHILD’S BLOOD, AND BREASTMILK). IN AIM 2, WE WILL CLARIFY THE JOINT EFFECTS OF MATERNAL PRENATAL DIETARY PATTERNS AND THE 24-HOUR MOVEMENT AND CHILD GROWTH, OBESITY, AND ND, AND WHETHER METABOLOMIC SIGNATURES PRENATALLY, AT BIRTH, AND POSTNATALLY MEDIATE THESE ASSOCIATIONS. FOR AIMS 1 AND 2 WE WILL ALSO EXAMINE HOW ASSOCIATIONS VARY BY NEIGHBORHOOD CHARACTERISTICS. IN AIM 3 WE WILL MAXIMIZE RECRUITMENT AND RETENTION BY IMPLEMENTING EVIDENCE-BASED STRATEGIES FOCUSED ON ENGAGING GROUPS IN CLINICAL RESEARCH AND IMPLEMENTING THE ECHO COHORT PROTOCOL APPLYING SYSTEMATIC QUALITY CONTROL APPROACHES AND BEST PRACTICES. WE PROPOSE TO CONTRIBUTE TO THE ECHO PROGRAM BY RECRUITING A LARGE COHORT OF 1,800 PREGNANT WOMEN FROM TWO MEDICAL CENTERS AT KAISER PERMANENTE NORTHERN CALIFORNIA SERVING A LARGE UNDERLYING POPULATION, THE CONCEIVING PARTNER, THEIR RESULTING CHILD, AND TO FOLLOW ALL OF THEM AT MULTIPLE VISITS AFTER THE CHILD IS BORN. IN AIM 4 WE WILL EXPLORE THE ROLE OF PRECONCEPTION MATERNAL AND PATERNAL LIFESTYLE FACTORS ON INFANT BIRTH SIZE TO IDENTIFY CRITICAL TIME PERIODS TO INTERVENE ON TO PREVENT UPSTREAM RISK FACTORS FOR CHILDHOOD OBESITY AND ND. ALL MEMBERS OF OUR RESEARCH TEAM WILL HAVE THE OPPORTUNITY TO CONTRIBUTE TO ALL ASPECTS OF OUR PROJECT AND TO BE INVOLVED IN THE NEW ECHO PHASE. FINDINGS FROM THIS STUDY WILL HAVE IMPORTANT IMPLICATIONS FOR INFORMING INTERVENTIONS, PREVENTION STRATEGIES AND POLICIES TO ENSURE OPTIMAL HEALTH AND WELL-BEING FOR ALL CHILDREN.

PATIENT-CENTERED TEAM-BASED PRIMARY CARE TO TREAT OPIOID USE DISORDER, DEPRESSION, AND OTHER CONDITIONS

EPIDEMIOLOGY OF AGE-RELATED DEMENTIA, MILD COGNITIVE IMPAIRMENT AND BRAIN PATHOLOGY IN A MULTIETHNIC COHORT OF OLDEST-OLD

PROSPECTIVE STUDY OF BREAST CANCER SURVIVORSHIP

TAILORED NON-PHARMACOTHERAPY SERVICES FOR CHRONIC PAIN: TESTING SCALABLE AND PRAGMATIC APPROACHES

MULTI-ETHNIC GENOME-WIDE STUDY OF BIPOLAR DISORDER

CLINICAL CARE GAPS AND UNMET NEEDS IN ADOLESCENT AND YOUNG ADULT (AYA) CANCERS

THE DISCOVERING HEALTHCARE INNOVATIONS TO ADDRESS DISPARTIES IN STROKE (DIADS) PR

ENHANCING OUTBREAK ANALYTICS AND FORECASTING WITH ELECTRONIC HEALTH RECORDS

MENTAL HEALTH RESEARCH NETWORK III

EARLY LIFE EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS AND CHILD GROWTH, ADIPOSITY, AND NEURODEVELOPMENT

OPTIMIZING COLONOSCOPY & FECAL IMMUNOCHEMICAL TESTS FOR COMMUNITY-BASED SCREENING

PRAGMATIC TRIAL OF ACUPUNCTURE FOR CHRONIC LOW BACK PAIN IN OLDER ADULTS

MULTI-INSTITUTIONAL CONSORTIUM FOR CER IN DIABETES TREATMENT AND PREVENTION

ENHANCING CLINICAL EFFECTIVENESS RESEARCH WITH NATURAL LANGUAGE PROCESSING OF EMR

HMORN UCSF CENTER FOR DIABETES TRANSLATIONAL RESEARCH

COMPARATIVE EFFECTIVENESS OF DIABETES PREVENTION STRATEGIES IN WOMEN WITH GDM

SCALABLE PARTNERING NETWORK FOR CER: ACROSS LIFESPAN CONDITIONS AND SETTINGS

CLINICAL IMPLEMENTATION OF CARRIER TESTING USING NGS

COLLABORATIVE CARE FOR CHRONIC PAIN IN PRIMARY CARE

STUDYING COLORECTAL CANCER EFFECTIVENESS OF SCREENING STRATEGIES (SUCCESS)

DEVELOPMENT OF A CARDIOVASCULAR SURVEILLANCE SYSTEM IN THE CVRN

HMO RESEARCH NETWORK CARDIOVASCULAR RESEARCH NETWORK

MULTIETHNIC STUDY OF BREAST ARTERIAL CALCIUM GRADATION AND CVD

PROMOTING ADHERENCE TO IMPROVE EFFECTIVENESS OF CARDIOVASCULAR DISEASE THERAPIES

PRECONCEPTION AND PRENATAL HEALTH IMPACTING FACTORS AND CHILD HEALTH - ABSTRACT CHILDHOOD OBESITY AND NEURODEVELOPMENTAL IMPAIRMENTS HAVE INCREASED IN RECENT DECADES AND ARE THE MOST PREVALENT CONDITIONS THREATENING CHILD’S HEALTH AND WELL-BEING. THE CONSEQUENCES OF THESE CONDITIONS SIGNIFY THE NEED TO IDENTIFY MODIFIABLE FACTORS TO TARGET FOR UPSTREAM PREVENTION. EMERGING EVIDENCE SUGGESTS THAT PRENATAL EXPOSURES TO PSYCHOLOGICAL DISTRESS, SUBSTANCE USE, AND LIFESTYLE FACTORS DURING CRITICAL WINDOWS OF FETAL DEVELOPMENT MAY OPERATE TO DEVELOPMENTALLY PROGRAM CHILDHOOD OBESITY AND NEURODEVELOPMENT (ND). HOWEVER, FEW STUDIES HAVE TAKEN A MULTIPLE EXPOSURE APPROACH TO UNDERSTAND THE INDIVIDUAL AND JOINT EFFECTS OF THESE EXPOSURES. IN AIM 1 WE WILL EXAMINE THE ROLE OF IN UTERO EXPOSURE TO PSYCHOLOGICAL DISTRESS AND SUBSTANCE USE ON CHILD GROWTH, ADIPOSITY, OBESITY, AND ND AND THE EXTENT TO WHICH PRENATAL LIFESTYLE FACTORS AND NEIGHBORHOOD FACTORS MAY MITIGATE THESE ASSOCIATIONS. FURTHER, WHILE MATERNAL DIET AND PHYSICAL ACTIVITY IMPACT INFANT GROWTH AND ADIPOSITY, FEW STUDIES IN DIVERSE POPULATIONS HAVE ASSESSED MECHANISTIC PATHWAYS AND LITTLE IS KNOWN ABOUT THEIR IMPACT ON ND. WE PROPOSE THE 24-HOUR MOVEMENT PROFILE AND METABOLOMICS AS OUR SPECIALIZED MEASURES OF LIFESTYLE, AND OBESITY AND ND AS OUR SPECIALIZED OUTCOMES. THE 24-HOUR MOVEMENT PROFILE INCORPORATES THE INTERDEPENDENT RELATIONSHIPS BETWEEN DEVICE-BASED MEASURES OF PHYSICAL ACTIVITY AND SLEEP DURING PREGNANCY TO BETTER INFORM INTERVENTIONS. METABOLOMICS CAN ELUCIDATE MECHANISTIC PATHWAYS AND WILL BE MEASURED REPEATEDLY ON THE SAMPLES COLLECTED ACCORDING TO THE ECHO PROTOCOL (PRENATAL BLOOD, CORD BLOOD, POSTNATAL CHILD’S BLOOD, AND BREASTMILK). IN AIM 2 WE WILL CLARIFY THE JOINT EFFECTS OF MATERNAL PRENATAL DIETARY PATTERNS AND THE 24-HOUR MOVEMENT AND CHILD GROWTH, OBESITY, AND ND AND WHETHER METABOLOMIC SIGNATURES PRENATALLY, AT BIRTH, AND POSTNATALLY MEDIATE THESE ASSOCIATIONS. FOR AIMS 1 AND 2 WE WILL ALSO EXAMINE HOW ASSOCIATIONS VARY BY NEIGHBORHOOD CHARACTERISTICS AND INFANT SEX ASSIGNED AT BIRTH. IN AIM 3 WE WILL MAXIMIZE RECRUITMENT AND RETENTION BY IMPLEMENTING EVIDENCE-BASED STRATEGIES FOCUSED ON ENGAGING DIVERSE GROUPS IN CLINICAL RESEARCH AND IMPLEMENTING THE ECHO COHORT PROTOCOL APPLYING SYSTEMATIC QUALITY CONTROL APPROACHES AND BEST PRACTICES. WE PROPOSE TO CONTRIBUTE TO THE ECHO PROGRAM BY RECRUITING A DIVERSE COHORT OF 1,800 PREGNANT INDIVIDUALS FROM TWO MEDICAL CENTERS AT KAISER PERMANENTE NORTHERN CALIFORNIA SERVING A DIVERSE POPULATION (~70% RACIAL/ETHNIC MINORITY GROUPS WITH 50% HAVING A LOW INCOME), THE CONCEIVING PARTNER, THEIR RESULTING CHILD, AND TO FOLLOW ALL OF THEM AT MULTIPLE VISITS AFTER THE CHILD IS BORN. IN AIM 4 WE WILL EXPLORE THE ROLE OF PRECONCEPTION MATERNAL AND PATERNAL LIFESTYLE FACTORS ON INFANT BIRTH SIZE TO IDENTIFY CRITICAL TIME PERIODS TO INTERVENE ON TO PREVENT UPSTREAM RISK FACTORS FOR CHILDHOOD OBESITY AND ND. ALL MEMBERS OF OUR DIVERSE RESEARCH TEAM WILL HAVE EQUAL OPPORTUNITY TO CONTRIBUTE TO ALL ASPECTS OF OUR PROJECT AND TO BE INVOLVED IN THE NEW ECHO PHASE. FINDINGS FROM THIS STUDY WILL HAVE IMPORTANT IMPLICATIONS FOR INFORMING INTERVENTIONS, PREVENTION STRATEGIES AND POLICIES TO ENSURE OPTIMAL HEALTH AND WELL-BEING FOR ALL CHILDREN.

CRN CLINICAL COMMUNICATION RESEARCH CENTER

PEDIATRIC RESPIRATORY ILLNESS INPATIENT MEASUREMENT SYSTEM STUDY

STRATEGIES AND OPPORTUNITIES TO STOP COLON CANCER IN PRIORITY POPULATIONS

PROSPECTIVE ANNUAL ESTIMATES OF INFLUENZA VACCINE EFFECTIVENESS AND BURDEN OF DISEASE

DIET AND LIFESTYLE IN A PROSPECTIVE STUDY OF BLADDER CANCER SURVIVORS

CONTEMPORARY TREATMENT AND OUTCOMES FOR ATRIAL FIBRILLATION IN CLINICAL PRACTICE

CALIFORNIA CADDRE-SEED PHASE II

THE CYGNET STUDY: ENVIROMENTAL AND GENETIC DETERMINANTS OF MATURATION OF GIRLS

BREAST WHITE ADIPOSE TISSUE INFLAMMATION AND BREAST CANCER OUTCOMES

THE CENTER EDUCATION AND RESEARCH ON THERAPEUTICS (CERTS) SCIENTIFIC FORUM

IMPACT OF INTEGRATED HEALTH IT ON QUALITY AND RESOURCE USE FOR DIABETIC PATIENTS

RESISTANCE TRAINING TO REDUCE CHEMOTOXICITY IN COLON CANCER

LOW-COST DETECTION OF DEMENTIA USING ELECTRONIC HEALTH RECORDS DATA: VALIDATION AND TESTING OF THE ERADAR ALGORITHM IN A PRAGMATIC, PATIENT-CENTERED TRIAL.

PROSPECTIVE EVALUATION OF ACUTE KIDNEY INJURY (PEAK) COHOT

(PQ3) ADDRESSING CANCER TREATMENT DISPARITIES FOR PERSONS WITH HIV - PROJECT SUMMARY/ABSTRACT THE INTRODUCTION OF COMBINATION ANTIRETROVIRAL THERAPY (ART) HAS LED TO A DRAMATIC DECLINE IN AIDS-ASSOCIATED MORTALITY. HOWEVER, AS PERSONS WITH HIV (PWH) AGE, MORTALITY FROM NON-AIDS-DEFINING CANCER (NADC) CONTINUES TO INCREASE AND IS NOW THE LEADING CAUSE OF DEATH FOR PWH. RECENT STUDIES HAVE DEMONSTRATED PERSISTENT DISPARITIES IN BOTH INITIATION OF CANCER THERAPY AND SURVIVAL AMONG PWH AND CANCER COMPARED WITH THE GENERAL POPULATION. THIS MAY BE DUE IN PART TO MEDICAL AND RADIATION ONCOLOGISTS' CONCERNS REGARDING THE SAFETY AND EFFICACY OF CANCER TREATMENT FOR PWH. ALTERNATIVELY, IT IS POSSIBLE THAT CHEMOTHERAPY WITH RADIATION THERAPY (CRT) AND RADIATION THERAPY (RT) ALONE MAY BE LESS EFFECTIVE IN PWH OR ASSOCIATED WITH GREATER TOXICITY. IT IS WELL ESTABLISHED THAT POSITIVE CANCER OUTCOMES ARE DEPENDENT ON SUCCESSFUL NAVIGATION OF ALL STEPS IN THE CANCER CARE DELIVERY PROCESS, INCLUDING: TIMELY TREATMENT INITIATION, TREATMENT COMPLETION, AND TREATMENT SAFETY, DEFINED BY AVOIDANCE OF SERIOUS ADVERSE EVENTS (SAES). IT IS ALSO CRITICAL TO EVALUATE THE ONGOING HEALTH NEEDS OF CANCER SURVIVORS WITH HIV, INCLUDING THE RISK OF LONG-TERM CHRONIC HEALTH CONDITIONS (I.E., LATE ADVERSE EFFECTS) AFTER CANCER TREATMENT. PRIOR STUDIES HAVE EVALUATED CANCER TREATMENT INITIATION RATES FOR CERTAIN CANCERS, HOWEVER, THERE HAVE BEEN NO PUBLISHED STUDIES THAT HAVE COMPREHENSIVELY EVALUATED DIFFERENCES IN OUTCOMES AT OTHER KEY STEPS IN THE CANCER CARE DELIVERY PROCESS FOR PWH COMPARED WITH PEOPLE WITHOUT HIV (HIV-), NOR HAVE THERE BEEN STUDIES THAT HAVE EVALUATED PATIENT- AND PROVIDER-FACTORS THAT MIGHT CONTRIBUTE TO DISPARITIES AT EACH STEP. WE PROPOSE THE FOLLOWING SPECIFIC AIMS WHICH WILL ADDRESS THESE CRITICAL KNOWLEDGE GAPS FOR THE FOUR MOST COMMON NADCS IN PWH TREATED WITH CRT/RT (ANAL, HEAD AND NECK, LUNG, OR PROSTATE CANCER): AIM 1: TO EVALUATE DIFFERENCES IN THE TIMING OF CANCER TREATMENT INITIATION BETWEEN PWH AND MATCHED HIV- WITH CANCER, AND RISK FACTORS FOR DELAYED TREATMENT IN PWH. AIM 2: TO EVALUATE DISPARITIES IN SHORT-TERM SAES AND CANCER TREATMENT COMPLETIONS BETWEEN PWH AND MATCHED HIV- PATIENTS WHO INITIATED CRT/RT. AIM 3: TO EVALUATE THE LONG-TERM RISK OF MORTALITY AND CANCER RECURRENCE COMPARING PWH WITH CANCER AND MATCHED HIV- PATIENTS. AIM 4: TO COMPARE RISK OF CHRONIC HEALTH CONDITIONS AMONG PWH WITH CANCER, WITH (A) HIV- WITH CANCER AND (B) PWH WITHOUT CANCER. IN ADDITION TO EVALUATING DIFFERENCES IN OUTCOMES BETWEEN PWH AND HIV- PATIENTS WITH CANCER, STUDY AIMS WILL ALSO EVALUATE THE IMPACTS OF KEY POTENTIAL RISK FACTORS, INCLUDING: ART REGIMENS, IMMUNOSUPPRESSION, AND TREATMENT DOSAGE AND COMPLETION, WHICH MAY BE ASSOCIATED WITH CRT/RT OUTCOMES. THIS OBSERVATIONAL COHORT STUDY WILL IDENTIFY >3,000 PWH DIAGNOSED WITH CANCER, 1:1 MATCHED HIV- PERSONS WITH THE SAME CANCERS, AND 4:1 MATCHED PWH WITHOUT CANCER WHO HAVE RECEIVED CARE FROM THE VETERAN'S ADMINISTRATION OR KAISER PERMANENTE, THE TWO LARGEST SINGLE-PAYER INTEGRATED HEALTHCARE SYSTEMS IN THE UNITED STATES. STUDY FINDINGS WILL PROVIDE DATA TO PROVIDE TARGETS FOR CANCER CARE DELIVERY AND TREATMENT INTERVENTIONS, AND INFORM HIV-SPECIFIC CANCER TREATMENT GUIDELINES TO IMPROVE CANCER SURVIVAL AMONG PWH.

COMPARATIVE EFFECTIVENESS IN GENOMIC & PERSONALIZED MEDICINE FOR COLON CANCER

PREDICTION ALGORITHMS FOR THE DETECTION OF EARLY STAGE PANCREATIC CANCER (PRO-TECT)

A NEW APPROACH TO AN OLD PROBLEM: REDESIGNING LATENT TUBERCULOSIS SCREENING AND TREATMENT

HARNESSING ARTIFICIAL INTELLIGENCE AND DEEP LEARNING TO DETERMINE A CORONARY ARTERY CALCIUM ESTIMATE IN PATIENTS WITH NO HISTORY OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (HIDDEN-ASCVD) STUDY - PROJECT SUMMARY/ ABSTRACT DATA SCIENCE ADVANCES HAVE LED TO THE EMERGENCE OF OPPORTUNISTIC IMAGING SCREENING – APPLYING ALGORITHMS TO SCREEN FOR CONDITIONS FROM IMAGING PERFORMED FOR OTHER PURPOSES. OPPORTUNISTIC SCREENING FOR CORONARY ARTERY CALCIUM (CAC) IS AN IDEAL TEST CASE. CAC IS THE STRONGEST PREDICTOR OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) AND KNOWING ONE HAS CAC CAN BE A POWERFUL MOTIVATOR OF PREVENTIVE BEHAVIOR. HOWEVER, <1% OF POTENTIALLY ELIGIBLE PATIENTS RECEIVE ELECTROCARDIOGRAM (ECG)-GATED COMPUTED TOMOGRAPHY (CT) SCANS TO MEASURE CAC. CAC CAN BE IDENTIFIED ON NON-GATED CHEST CTS, OF WHICH 19 MILLION ARE PERFORMED ANNUALLY IN THE U.S. WE PREVIOUSLY DEMONSTRATED THAT A DEEP LEARNING (DL) ALGORITHM CAN ACCURATELY QUANTIFY CAC ON NON- GATED, NON-CONTRAST CHEST CTS, AND NOTIFYING PATIENTS AND PROVIDERS OF THE PRESENCE OF OPPORTUNISTIC CAC SIGNIFICANTLY INCREASED STATIN PRESCRIPTION RATES COMPARED TO USUAL CARE. THE HIDDEN-ASCVD STUDY WILL EXTEND VALIDATED DL-CAC METHODS TO NON-CARDIAC, CONTRAST-ENHANCED CT SCANS AND INCLUDE A FACTORIAL RANDOMIZED CONTROLLED TRIAL (RCT) TO IDENTIFY THE OPTIMAL OPPORTUNISTIC CAC NOTIFICATION STRATEGIES TO MAXIMIZE STATIN PRESCRIPTION RATES AND PATIENT AND PROVIDER ACCEPTABILITY WITHIN KAISER PERMANENTE NORTHERN CALIFORNIA, AN INTEGRATED HEALTH SYSTEM PROVIDING CARE TO >4.5 MILLION MEMBERS WITH BROAD RACIAL AND ETHNIC DIVERSITY. IN AIM 1, WE WILL VALIDATE THE DIAGNOSTIC ACCURACY OF THE EXISTING DL-CAC ALGORITHM AND ADAPT THE ALGORITHM TO CONTRAST-ENHANCED CT SCANS USING SELF-SUPERVISED DL AND PAIRED NON-GATED AND GATED CT SCANS. WE WILL ALSO DESCRIBE THE EPIDEMIOLOGY AND OUTCOMES OF OPPORTUNISTIC CAC IN THIS DIVERSE HEALTH CARE SYSTEM. IN AIM 2, WE WILL IDENTIFY 5,760 ADULTS WITH DL-CAC ON CHEST CT, WITHOUT KNOWN ASCVD, AND NOT RECEIVING STATINS AND EFFICIENTLY TEST MULTIPLE NOTIFICATION STRATEGIES BASED ON THE MINDSPACE BEHAVIOR CHANGE PRINCIPLES AND THE MULTIPHASE OPTIMIZATION STRATEGY (MOST) FRAMEWORK FOR INTERVENTION OPTIMIZATION. THROUGH A FACTORIAL RCT DESIGN, WE WILL DETERMINE THE MOST EFFECTIVE NOTIFICATION STRATEGY THAT MAXIMIZES STATIN THERAPY AND MINIMIZES PATIENT-REPORTED ANXIETY. CO-DESIGN FOCUS GROUPS OF PROVIDERS AND PATIENTS THAT RECEIVED NOTIFICATIONS WILL THEN PROVIDE INPUT ON SERIAL ADAPTATION OF THE STRATEGY BASED ON THEIR EXPERIENCE. THE ADAPTED OPTIMAL STRATEGY WILL BE TESTED IN A SINGLE-ARM VALIDATION STUDY TO DETERMINE AN UNBIASED ESTIMATE OF THE NET EFFECT OF THE INTERVENTION ON STATIN INITIATION AND PATIENT ACCEPTABILITY. THE RCTS WILL BE ENRICHED FOR HISTORICALLY MARGINALIZED RACIAL AND ETHNIC GROUPS TO PROVIDE GENERALIZABLE KNOWLEDGE. THE HIDDEN-ASCVD STUDY WILL BE PARADIGM SHIFTING BY IDENTIFYING THE OPTIMAL BEHAVIORAL SCIENCE-DRIVEN NOTIFICATION STRATEGY FOR OPPORTUNISTIC CAC BALANCING THE BENEFIT OF STATIN THERAPY WITH THE PERCEIVED RISKS OF HEALTH-RELATED ANXIETY. THIS RESEARCH WILL MOTIVATE FUTURE STUDIES DESIGNED TO IMPLEMENT OPPORTUNISTIC CAC SCREENING AND NOTIFICATION ON A HEALTH SYSTEM-WIDE SCALE REDUCING THE OVERALL BURDEN OF ASCVD AND MITIGATING DOCUMENTED HEALTH DISPARITIES.

IDENTIFYING PRE-SEPSIS OPPORTUNITIES FOR EARLY, TARGETED INTERVENTION

MODERATE HYPERTENSION IN PREGNANCY: SAFETY AND EFFECTIVENESS OF TREATMENT

DIGITAL TREATMENTS FOR OPIOIDS AND OTHER SUBSTANCE USE DISORDERS (DIGITS) IN PRIMARY CARE: A HYBRID TYPE-III IMPLEMENTATION TRIAL

NATIONAL CADDRE STUDY: CHILD DEVELOPMENT AND AUTISM

CV WIZARD: DOES A PRIORITIZED, POINT-OF-CARE CLINICAL DECISION SUPPORT TOOL IMPROVE GUIDELINE-BASED CVD RISK FACTOR CONTROL IN SAFETY NET CLINICS?

ANTIMICROBIAL RESISTANT E. COLI BEFORE AND AFTER CALIFORNIA SENATE BILL 27 (ARES): A NATURAL EXPERIMENT

INPATIENT TECHNOLOGY-SUPPORTED ASSISTED REFERRAL

NAD+ AUGMENTATION IN CARDIAC SURGERY ASSOCIATED MYOCARDIAL INJURY

BLOOD PRESSURE, OBESITY, AND DIABETES IN RELATION TO PERINATAL AND POSTPARTUM COMPLICATIONS - PROJECT SUMMARY/ABSTRACT HYPERTENSIVE DISORDERS IN PREGNANCY (HDP) ARE A LEADING CAUSE OF MATERNAL MORBIDITY, AFFECTING OVER 350,000 PREGNANT U.S. WOMEN ANNUALLY. HDP RATES INCREASED DRAMATICALLY IN THE PAST DECADES. CLINICAL CARE AND MANAGEMENT FOR THIS GROWING GROUP OF WOMEN IS COMPLICATED, HOWEVER, BY CONFLICTING GUIDELINES, UNCERTAIN EVIDENCE FOR POSTPARTUM CARE, AND IMPORTANT COMORBIDITIES THAT MAY IMPACT OUTCOMES. IN 2017, THE AMERICAN COLLEGE OF CARDIOLOGY/AMERICAN HEART ASSOCIATION (ACC/AHA) ISSUED NEW GUIDELINES TO DEFINE CHRONIC HYPERTENSION BY USING LOWER SYSTOLIC/DIASTOLIC BLOOD PRESSURE (SBP/DBP) THRESHOLDS (STAGE 1 HYPERTENSION, 130-139/80-89; STAGE 2, =140/90 MMHG) DOWN FROM =140/90. IN 2019, THE AMERICAN COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS (ACOG) CONFIRMED MUCH OF THIS RECOMMENDATION BUT DID NOT APPLY THE LOWER BP THRESHOLDS TO DIAGNOSE NEW-ONSET HDP, DUE TO THE LACK OF DATA ON THE ASSOCIATIONS BETWEEN THESE LOWER BP THRESHOLDS WITH PRENATAL AND POSTPARTUM COMPLICATION. THE ACOG ALSO RECOGNIZED IT IS NOT SCIENTIFICALLY SUBSTANTIATED TO USE THE 20-WEEK MARK TO DETERMINE WHETHER HYPERTENSION PREDATES PREGNANCY OR IS PREGNANCY-RELATED, CALLING FOR EXAMINATION OF BP TRAJECTORIES ACROSS PREGNANCY. FURTHER, DUE TO FRAGMENTED POSTPARTUM CARE, LITTLE IS KNOWN ABOUT POSTPARTUM HYPERTENSIVE DISORDERS AND ASSOCIATED HOSPITALIZATION AND SEVERE MATERNAL MORBIDITY. FINALLY, PRE-EXISTING OBESITY AND DIABETES OFTEN CLUSTER WITH HDP AND COMPLICATE THE ASSOCIATION BETWEEN BP IN PREGNANCY AND RISK OF COMPLICATIONS. TO ADDRESS THESE CRITICAL KNOWLEDGE GAPS, WE PROPOSE A POPULATION- BASED COHORT STUDY OF ~0.5 MILLION DEMOGRAPHICALLY DIVERSE WOMEN WHO DELIVERED SINGLETONS IN 2007-2019 AT KAISER PERMANENTE NORTHERN CALIFORNIA (KPNC), AN INTEGRATED HEALTH CARE SYSTEM WITH A STABLE MEMBERSHIP AND COMPREHENSIVE ELECTRONIC MEDICAL RECORD DATA. WE ARE UNIQUELY POSITIONED TO TIMELY ADDRESS THE IMPORTANT CONCERN REGARDING THE UNKNOWN ASSOCIATION OF THE 2017 ACC/AHA DEFINED BP CATEGORIES IN PREGNANCY WITH PERINATAL AND POSTPARTUM COMPLICATIONS (AIMS 1-2). LEVERAGING KPNC’S UNIQUE LONGITUDINAL TRACKING OF BP AND WEIGHT BEFORE, DURING, AND AFTER PREGNANCY AND ROBUST DIABETES DIAGNOSIS DATA BEFORE PREGNANCY, WE WILL BE ABLE TO EFFICIENTLY DISSECT THE JOINT EFFECTS OF BP IN PREGNANCY WITH COMORBID OBESITY AND DIABETES ON PERINATAL AND POSTPARTUM COMPLICATIONS (AIMS 1-2). FINALLY, WE WILL EXAMINE BP TRAJECTORIES ON A CONTINUUM BEFORE 20 WEEKS OF GESTATION AND ACROSS PREGNANCY WITH RISK OF COMPLICATIONS (AIM 3). THIS STUDY PROVIDES A TIMELY AND UNPARALLELED OPPORTUNITY TO ADDRESS THE CONCERNS ARISING FROM THE CONFLICTS BETWEEN THE ACC/AHA AND ACOG GUIDELINES REGARDING HOW TO MANAGE PREGNANT WOMEN WITH BP LEVELS LOWER THAN CONVENTIONAL THRESHOLDS. OUR FINDINGS MAY HELP IDENTIFY AT WHICH BP LEVEL, AND IN WHICH TIME WINDOW, CLOSER PATIENT SURVEILLANCE AND CHANGE IN MANAGEMENT MAY BE INITIATED. FURTHER, OUR FINDINGS MAY PROVIDE CLINICIANS WITH SORELY NEEDED DATA TO INFORM EARLY CLINICAL TRIAGE AND RISK STRATIFICATION OF WOMEN WITH COMBINATIONS OF CERTAIN BP CATEGORIES IN PREGNANCY AND COMORBID OBESITY AND DIABETES, THUS ENHANCING INDIVIDUALIZED CARE DECISION AND EFFICIENCY.

THE EPICS (ENGAGING PRIMARY CARE IN CANCER SURVIVORSHIP) STUDY: A RANDOMIZED TRIAL OF NOVEL MODELS OF CARE FOR CANCER SURVIVORS

CLINICAL TRIAL OF EXPANDED ADVANCE CARE PLANNING TO ADDRESS REGIMEN INTENSITY IN OLDER PATIENTS AT HIGH RISK FOR TREATMENT-INDUCED HYPOGLYCEMIA

CAF????????: CLINIC-BASED INTERVENTION TO ADDRESS FINANCIAL HARDSHIP FOR PEOPLE WITH CANCER

REDUCING WEIGHT AND DIABETES RISK IN AN UNDERSERVED POPULATION

AN EFFICACY-EFFECTIVENESS TRIAL OF COGNITIVE BIAS MODIFICATION FOR YOUTH ANXIETY

MOLECULAR PROFILES AND LIFESTYLE FACTORS IN BREAST CANCER PROGNOSIS

SPREAD-NET: PRACTICES ENABLING ADAPTING AND DISSEMINATING IN THE SAFETY NET

THE SAFETY AND IMPACT OF EXPANDED ACCESS TO NALOXONE IN HEALTH SYSTEMS

MATERNAL MARIJUANA USE DURING PREGNANCY, MARIJUANA LEGALIZATION, AND ADVERSE OBSTETRICAL AND NEONATAL OUTCOMES: A 12-YEAR COHORT STUDY

ASCEND: APPROACHES TO CHC IMPLEMENTATION OF SDH DATA COLLECTION AND ACTION

PREDICITING AND ADDRESSING COLONOSCOPY NON-ADHERENCE IN COMMUNITY SETTINGS

BODY COMPOSITION AND BREAST CANCER SURVIVAL: IMMUNE AND METABOLIC BIOMARKERS IN BREAST TUMORS

IMPROVING BLOOD PRESSURE SCREENING AND TREATMENT STRATEGIES IN YOUNG ADULTS - PROJECT SUMMARY THE OVERALL REDUCTION IN THE RATE OF CARDIOVASCULAR DISEASE (CVD) OVER THE PAST DECADES IN THE US HAS NOT EXTENDED TO YOUNG ADULTS AGED 18-39 YEARS. AN INCREASING PREVALENCE OF CVD RISK FACTORS IN YOUNG ADULTS, INCLUDING HIGH BLOOD PRESSURE (BP), LIKELY CONTRIBUTED TO THE INCREASE IN CVD RATES. ABOUT 20% OF US YOUNG ADULTS HAVE STAGE 1 OR 2 HYPERTENSION (BP 130-139/80-89 MM HG AND =140/90 MM HG, RESPECTIVELY). DESPITE THE HIGH PREVALENCE OF HYPERTENSION IN YOUNG ADULTS AND ITS ASSOCIATION WITH CVD, THERE IS LITTLE EVIDENCE TO GUIDE BP SCREENING AND TREATMENT RECOMMENDATIONS IN YOUNG ADULTS. FOR BP SCREENING, >25% OF YOUNG ADULTS IN THE US WITH HYPERTENSION ARE UNAWARE THAT THEY HAVE IT. MOREOVER, SOCIAL DETERMINANTS OF HEALTH (SDOH), AN IMPORTANT INFLUENCE ON THE HEALTH OF YOUNG ADULTS, IS NOT CONSIDERED IN BP SCREENING RECOMMENDATIONS. FOR BP MANAGEMENT, THE BENEFITS OF INITIATING ANTIHYPERTENSIVE MEDICATIONS DURING YOUNG ADULTHOOD ARE UNKNOWN AND ARE EXTRAPOLATED FROM DATA AMONG OLDER ADULTS. DUE TO THE LACK OF EVIDENCE, MOST OF THE 13 MILLION YOUNG ADULTS WITH STAGE 1 HYPERTENSION ARE CURRENTLY NOT RECOMMENDED TO INITIATE ANTIHYPERTENSIVE MEDICATION, AND 50% (2.5 MILLION) OF YOUNG ADULTS WITH STAGE 2 HYPERTENSION ARE CURRENTLY LEFT UNTREATED. ALTHOUGH RANDOMIZED CONTROLLED TRIALS (RCTS) WITH HARD CVD OUTCOMES WILL PROVIDE DEFINITIVE EVIDENCE, IT MAY NOT BE FEASIBLE TO PERFORM SUCH A TRIAL IN YOUNG ADULTS DUE TO HIGH COSTS AND LONG FOLLOW-UP TIME NEEDED TO DETERMINE CVD RISK REDUCTION BENEFITS. IN THE ABSENCE OF RCTS, HIGH QUALITY OBSERVATIONAL AND SIMULATION STUDIES CAN PROVIDE CLINICALLY RELEVANT AND ACTIONABLE EVIDENCE FOR POLICY MAKERS, PATIENTS, AND CLINICIANS IN A COST-EFFICIENT MANNER. THE OVERALL STUDY OBJECTIVES ARE TO DETERMINE THE OPTIMAL BP SCREENING INTERVALS FOR YOUNG ADULTS AND TO IDENTIFY THOSE WITH A HIGH RISK OF PREMATURE AND/OR LIFETIME CVD WHO MAY BENEFIT FROM ANTIHYPERTENSIVE MEDICATION DURING YOUNG ADULTHOOD. THE AIMS OF THIS STUDY ARE TO (1) DETERMINE BP SCREENING INTERVALS BY EXAMINING THE TIMING OF TRANSITIONING FROM NORMAL BP INTO STAGE 1 OR 2 HYPERTENSION AND LONG-TERM BP TRAJECTORIES, (2) IDENTIFY CHARACTERISTICS OF YOUNG ADULTS WITH STAGE 1 OR 2 HYPERTENSION WHO ARE AT HIGH RISK FOR ADVERSE CVD OR RENAL OUTCOMES, (3) QUANTIFY THE BENEFITS AND HARMS OF ANTIHYPERTENSIVE MEDICATION AMONG YOUNG ADULTS WITH STAGE 1 OR 2 HYPERTENSION BY EMULATING A HYPOTHETICAL RCT USING A LARGE OBSERVATIONAL DATABASE AND STATE-OF-THE-ART STATISTICAL MODELS TO MINIMIZE CONFOUNDING AND SELECTION BIAS, AND (4) COMPARE THE SHORT- AND LONG-TERM HEALTH AND ECONOMIC IMPACT OF BP SCREENING AND MANAGEMENT STRATEGIES FOR US YOUNG ADULTS IDENTIFIED IN AIMS 1 TO 3 VS. CURRENT BP GUIDELINES. TO ADDRESS THESE AIMS, WE WILL STUDY ~500,000 YOUNG ADULTS AGED 18-39 YEARS FROM BOTH KAISER PERMANENTE SOUTHERN CALIFORNIA AND FOUR EPIDEMIOLOGIC COHORTS. FINDINGS FROM THIS STUDY WILL INFORM FUTURE BP GUIDELINES, REDUCE HEALTH INEQUITY BY DIRECTING SCREENING AND TREATMENT TO HIGH RISK SUBGROUPS, AND IMPROVE CARDIOVASCULAR HEALTH OF US YOUNG ADULTS.

HEALTH SYSTEM DEPRESSION TREATMENT AND OUTCOMES - ABSTRACT DEPRESSION WILL BE THE GREATEST SOURCE OF GLOBAL DISEASE BY 2030, AFFECTING BLACK, HISPANIC, AND ASIAN COMMUNITIES. OUR WORK HAS SHOWN THAT COMPARED TO WHITE PATIENTS, BLACK, HISPANIC, AND ASIAN PATIENTS WERE LESS LIKELY TO RECEIVE ANY DEPRESSION TREATMENT AND IF TREATED, LESS LIKELY TO RECEIVE A PARTIAL OR FULL COURSE OF PSYCHOTHERAPY OR MEDICATION. IF PATIENTS DO NOT RECEIVE TREATMENT, MOST WILL NOT EXPERIENCE IMPROVEMENT OR REMISSION OF THEIR DEPRESSION. HOWEVER, THE EVIDENCE IS NOT CLEAR ABOUT THE BENEFITS OF A PARTIAL VS FULL COURSE OF TREATMENT BECAUSE REAL-WORLD POPULATION-BASED STUDIES RARELY INCLUDE THE TREATMENT COURSE IN OUTCOME ANALYSES. TWO IMPORTANT UNANSWERED QUESTIONS FOR IMPLEMENTATION RESEARCH ON DEPRESSION TREATMENT DISPARITIES ARE 1) WHAT FACTORS CONTRIBUTE TO PATIENTS NOT RECEIVING TREATMENT AND 2) IF TREATED, DOES A PARTIAL COURSE CONFER SIMILAR BENEFITS TO A FULL COURSE? WE WILL ADDRESS THESE QUESTIONS BY USING 1) THE NIMHD FRAMEWORK ADAPTATION FOR DEPRESSION THAT ADDRESSES THE ROLE OF HEALTH SYSTEMS SPECIFICALLY TO ESTABLISH THE DETERMINANTS OF DISPARITIES IN DEPRESSION TREATMENT AND OUTCOMES AND 2) A LEARNING HEALTH SYSTEMS APPROACH TO ENSURE OUR FINDINGS HAVE AN IMPACT ON PRACTICE. THE FOLLOWING AIMS WILL BE ACCOMPLISHED WITH A SAMPLE OF BLACK (N=44,934), HISPANIC (N=113,207), ASIAN (N=16,505), AND WHITE (N=179,502) PATIENTS IN 5 HEALTH SYSTEMS IN 7 STATES (CA,TX,GA,MN,MI,ND,WI): AIM 1. TEST THE FACTORS IN THE NIMHD FRAMEWORK FOR MENTAL HEALTH CONTRIBUTING TO RACIAL DISPARITIES IN TREATMENT (NONE, PARTIAL OR FULL COURSE) FOR PATIENTS WITH MODERATE-TO-SEVERE SYMPTOMS OF DEPRESSION; AIM 2. EXAMINE THE MEDIATING EFFECT OF TREATMENT ON RACIAL DISPARITIES IN IMPROVEMENT AND REMISSION OF DEPRESSION SYMPTOMS; AIM 3. ADDRESS FACTORS IN THE NIMHD FRAMEWORK FOR MENTAL HEALTH THAT CANNOT BE ADDRESSED IN MODELS FOR AIM 1 AND AIM 2 BY INCORPORATING THE LIVED EXPERIENCES OF BLACK, HISPANIC AND ASIAN PATIENTS AND THEIR PROVIDERS; AND AIM 4. COMBINE THE FINDINGS FROM AIMS 1 – 3 TO CREATE A SET OF RECOMMENDATIONS FOR RESEARCH AND PRACTICE TO IMPROVE DEPRESSION CARE IN LARGE HEALTH SETTINGS.

USE OF ACUPUNCTURE FOR CHRONIC PAIN WITHIN AN INTEGRATED HEALTH PLAN

PRENATAL AND NEONATAL BIOLOGIC MARKERS FOR AUTISM

TRANSLATIONAL DIABETES PREVENTION IN GDM

IMPACT OF BODY COMPOSITION AND RELATED INFLAMMATORY AND IMMUNE STATES ON PROGNOSIS OF NON-MUSCLE INVASIVE BLADDER CANCER - ABSTRACT BLADDER CANCER IS ONE OF THE TOP TEN MOST COMMON CANCERS IN THE U.S., AND ONE OF THE MOST EXPENSIVE TO TREAT. MOST CASES (75%) ARE NON-MUSCLE-INVASIVE BLADDER CANCER (NMIBC) WITH HIGH RATES OF RECURRENCE (70%) AND PROGRESSION (25%). WHILE PROGNOSTIC FACTORS REMAIN LARGELY UNKNOWN, THE SUCCESS OF BACILLUS CALMETTE-GUERIN (BCG), AN INTRAVESICAL IMMUNOTHERAPY AS THE MOST EFFECTIVE THERAPY FOR NMIBC FOR OVER FOUR DECADES, HIGHLIGHTS THE POTENTIAL OF THE INFLAMMATORY AND IMMUNE ENVIRONMENTS IN DETERMINING TREATMENT RESPONSE AND PROGNOSIS. GIVEN THE MEDIAN AGE OF BLADDER CANCER DIAGNOSIS IS 73 YEARS, PATIENTS ARE COMMONLY FACED WITH AGE-RELATED LOSS OF MUSCLE MASS (SARCOPENIA), INCREASE OF FAT ACCUMULATION (OBESITY), OR BOTH (SARCOPENIC OBESITY), WHICH ARE ALL CHARACTERIZED BY CHRONIC INFLAMMATION AND ALTERED IMMUNE RESPONSES. THESE BODY COMPOSITION PHENOTYPES ARE ASSOCIATED WITH TUMOR PROGRESSION AND INCREASED MORTALITY. THUS, WE HYPOTHESIZE THAT BODY COMPOSITION AT DIAGNOSIS MAY SHAPE THE HOST INFLAMMATORY AND IMMUNE MILIEU AND IMPACT BLADDER CANCER PROGNOSIS. THIS HYPOTHESIS WILL BE TESTED IN THE BLADDER CANCER EPIDEMIOLOGY, WELLNESS, AND LIFESTYLE STUDY (BE-WELL; R01 CA172855, MPI: KWAN/TANG/KUSHI) OF NEWLY DIAGNOSED NMIBC PATIENTS FROM 2015-2019 AT KAISER PERMANENTE, ONE OF THE LARGEST PROSPECTIVE COHORT STUDIES OF NMIBC, WITH 1,472 PATIENTS ENROLLED WITH RICH PATIENT, CLINICAL, AND BIOSPECIMEN DATA TO EXAMINE GENETIC AND LIFESTYLE FACTORS IN PROGNOSIS AND SURVIVAL. WE PROPOSE TO CONDUCT A FULL INVESTIGATION OF BODY COMPOSITION, INFLAMMATION, AND IMMUNITY IN BLADDER CANCER OUTCOMES IN BE-WELL TO DETERMINE HOW ADIPOSITY, MUSCLE, AND INFLAMMATORY AND IMMUNE BIOMARKERS AT DIAGNOSIS CAN IDENTIFY NMIBC PATIENTS AT HIGH RISK FOR TREATMENT FAILURE AND/OR DISEASE RECURRENCE AND PROGRESSION. OUR AIMS ARE: 1) TO DETERMINE THE ASSOCIATION OF COMPUTED TOMOGRAPHY (CT)-DERIVED BODY COMPOSITION PHENOTYPES (SARCOPENIA, ADIPOSITY, MYOSTEATOSIS) WITH NMIBC RECURRENCE (FIRST AND MULTIPLE) AND PROGRESSION; 2) TO DETERMINE THE ASSOCIATION OF BODY COMPOSITION WITH BCG IMMUNOTHERAPY OUTCOMES INCLUDING ADVERSE EVENTS AND TREATMENT FAILURE; 3) TO EXAMINE THE ASSOCIATION OF CIRCULATING INFLAMMATORY AND IMMUNE BIOMARKERS WITH BODY COMPOSITION AND BCG OUTCOMES AND NMIBC PROGNOSIS; 4) EXPLORE IF THE ADDITION OF BODY COMPOSITION MEASURES AND INFLAMMATORY AND IMMUNE BIOMARKERS IMPROVES THE PERFORMANCE OF CURRENT RISK STRATIFICATION MODELS FOR NMIBC PATIENTS. GIVEN THE COMMON CLINICAL USE OF CT, BODY COMPOSITION MEASURES COULD BE READILY INCORPORATED INTO THE CURRENT CLINICOPATHOLOGICAL FACTOR- BASED RISK STRATIFICATION SYSTEM TO IMPROVE THE CLINICAL CARE OF NMIBC.

ADDICTION TELEMEDICINE CONSULTATION IN PRIMARY CARE: INCREASING ACCESS TO PHARMACOTHERAPY AND SPECIALTY TREATMENT FOR ALCOHOL PROBLEMS

MULTI-COMPONENT BEHAVIORAL INTERVENTION FOR COMPLEX PATIENTS WITH CVD RISK

FETAL AND EARLY POSTNATAL INFLUENCES ON CHILD METABOLIC HEALTH AFTER GESTATIONAL DIABETES

MATERNAL INFLAMMATION DURING PREGNANCY AND NEURODEVELOPMENTAL DISORDERS

INTERNET CBT FOR DEPRESSION: COMPARING PURE, GUIDED, AND STEPPED CARE

HEALTHCARE ORGANIZATIONAL STRUCTURAL CONDITIONS AND THE HEALTH OF PEOPLE RECENTLY RELEASED FROM PRISON - PROJECT SUMMARY/ABSTRACT SOCIETAL SYSTEMS OF RACISM, SEGREGATION, AND CRIMINAL JUSTICE PRACTICES HAVE RESULTED IN HIGH RATES OF IMPRISONMENT OF BLACK, INDIGENOUS, AND OTHER PEOPLE OF COLOR (BIPOC) AND REPRESENT STRUCTURAL RACISM AND DISCRIMINATION (SRD). UPON RELEASE FROM PRISON, PEOPLE FACE FURTHER CHALLENGES INFLUENCED BY SRD INCLUDING POLICIES, PROCEDURES AND PRACTICES IN THE HEALTHCARE SYSTEM THAT LIMIT ACCESS AND CONTRIBUTE TO POOR HEALTH. COMPARED TO THE GENERAL POPULATION, PEOPLE RELEASED FROM PRISON HAVE A HIGHER PREVALENCE OF POOR CV HEALTH, AN INCREASED RISK OF CV EVENTS, AND HIGHER CARDIOVASCULAR (CV) MORTALITY WITHIN 2 YEARS OF RELEASE. ACCESS TO HEALTHCARE FOLLOWING RELEASE FROM PRISON IS KEY TO PREVENTING POOR HEALTH OUTCOMES IN THIS POPULATION. SYSTEMATIC INVESTIGATION OF SRD IN DIVERSE HEALTHCARE SYSTEMS HAS NOT OCCURRED, AND THE EXTENT TO WHICH DIFFERENT ORGANIZATIONAL POLICIES AND PRACTICES LIMIT OR PERPETUATE DISPARITIES IN ACCESS AND HEALTH OUTCOMES AMONG PEOPLE RELEASED FROM PRISON IS UNKNOWN. WE PROPOSE THREE SPECIFIC AIMS TO PROVIDE CRITICAL INFORMATION ON SRD IN HEALTHCARE ORGANIZATIONS AND BEGIN TO ADDRESS THE PROBLEM. IN AIM 1, USING THREE DIVERSE HEALTH SYSTEMS, WE WILL ANALYZE SYSTEM WRITTEN MATERIALS AND CONDUCT INTERVIEWS AND FOCUS GROUPS WITH SYSTEM LEADERS, FRONTLINE STAFF, AND REPRESENTATIVES OF COMMUNITY-BASED ORGANIZATIONS TO MEASURE POLICIES, PRACTICES AND ATTITUDES AROUND HEALTHCARE ACCESS, TRANSITION PROGRAMS, CULTURE, SUPPORT OF SOCIAL DETERMINANTS OF HEALTH AND SPECIALIZED SERVICES FOR PEOPLE RELEASED FROM PRISON. IN AIM 2, LEVERAGING A DATABASE OF INDIVIDUALS RELEASED FROM COLORADO STATE PRISONS (~400 A MONTH), WE WILL PROSPECTIVELY ENROLL 600 PEOPLE RECENTLY RELEASED FROM PRISON INTO A LONGITUDINAL COHORT STUDY TO ASSESS THEIR EXPOSURE TO HEALTHCARE STRUCTURAL CONDITIONS FOLLOWING RELEASE. USING THE ALL-PAYER CLAIMS DATABASE, WE WILL EXAMINE THE ASSOCIATION BETWEEN EXPOSURE TO STRUCTURAL CONDITIONS AND 12-MONTH PRIMARY OUTCOMES OF HEALTHCARE UTILIZATION (CLINIC VISITS, EMERGENCY VISITS, HOSPITALIZATION) AND SECONDARY OUTCOMES OF CV HOSPITALIZATION AND ALL-CAUSE MORTALITY. RACE/ETHNICITY AND BASELINE CV HEALTH WILL BE EXAMINED AS MODERATING VARIABLES BECAUSE INTERSECTIONAL SRD MAY PARTICULARLY DISADVANTAGE BIPOC INDIVIDUALS RELEASED FROM PRISON AND THOSE WITH POOR CV HEALTH. IN AIM 3, WE WILL INTEGRATE RESULTS FROM AIMS 1 AND 2 TO DEVELOP PRACTICE RECOMMENDATIONS TO IMPROVE HEALTH CARE ACCESS AND OUTCOMES FOR PEOPLE RELEASED FROM PRISON. RECOMMENDATIONS WILL BE ITERATIVELY REVISED WITH A COMMUNITY ADVISORY BOARD AND FINALIZED USING A MODIFIED DELPHI PANEL OF NATIONAL EXPERTS. FINAL RECOMMENDATIONS WILL BE ASSEMBLED AND BROADLY DISSEMINATED. GIVEN THE ENORMITY OF THE POPULATION OF INDIVIDUALS WITH A HISTORY OF IMPRISONMENT, THEIR SIGNIFICANT BURDEN OF POOR HEALTH INCLUDING CV DISEASE AND THE DISPROPORTIONATE IMPRISONMENT OF BIPOC INDIVIDUALS, A CRITICAL GOAL OF OUR RESEARCH IS TO IDENTIFY TARGETS FOR FUTURE INTERVENTIONS TO IMPROVE ACCESS AND HEALTH FOR PEOPLE RELEASED FROM PRISON. SOLUTIONS TO THE SIGNIFICANT PROBLEM OF NEGATIVE HEALTH CONSEQUENCES TO IMPRISONMENT AND SRD REQUIRES UNDERSTANDING STRUCTURAL CONDITIONS AT MULTIPLE LEVELS.

REDUCING CHILDHOOD OBESITY THROUGH EHR-SUPPORTED MOTIVATIONAL INTERVIEWING - PROJECT SUMMARY RATES OF CHILDHOOD OBESITY IN THE U.S. REMAIN AT HISTORIC HIGHS. BEFORE THE AGE OF 11 YEARS, 18% OF ALL CHILDREN IN THE U.S. ARE ALREADY OBESE; 26% OF HISPANIC AND 24% OF BLACK CHILDREN ARE OBESE. PEDIATRIC PRIMARY CARE SETTINGS ARE UNDERUTILIZED IN PREVENTING AND TREATING CHILDHOOD OBESITY. AN EVIDENCE-BASED METHOD FOR TREATMENT OF CHILDHOOD OBESITY TO HELP ENGAGE AND MOTIVATE PATIENTS IS MOTIVATIONAL INTERVIEWING (MI). ONE RECENT SUCCESSFUL STUDY, BMI2 (FOR BRIEF MOTIVATIONAL INTERVIEWING TO REDUCE CHILD BODY MASS INDEX) DIRECTED AT THE PARENTS OF CHILDREN IN PEDIATRIC CARE PRACTICES LOWERED BMI SIGNIFICANTLY. MI-BASED APPROACHES HAVE BEEN PARTICULARLY SUCCESSFUL FOR RACIAL/ETHNIC MINORITIES AND LOW-INCOME POPULATIONS. HOWEVER, THE TARGETED MI DOSE OF BMI2 REQUIRES SIGNIFICANT RESOURCES, WITH MI SESSIONS ADMINISTERED BY THE PCP AND A REGISTERED DIETICIAN. IT IS UNCLEAR WHETHER THE IMPRESSIVE RESULTS OF BMI2 CAN BE REPLICATED IN A HEALTH CARE SYSTEM WITH REAL-WORLD CONDITIONS. IT IS CHALLENGING TO FIND AN EFFECTIVE INTERVENTION THAT IS FEASIBLE AND SUSTAINABLE WITHOUT REQUIRING SIGNIFICANT RESOURCES. OUR OVERALL GOAL IS TO REDUCE EXCESS BODY WEIGHT IN CHILDREN IN PRIMARY CARE. WE WILL CONDUCT A CLUSTER-RANDOMIZED PRAGMATIC TRIAL IN 36 PEDIATRIC CLINICS IN KAISER PERMANENTE SOUTHERN CALIFORNIA (KPSC) TO TEST THE EFFECTIVENESS OF A MODIFIED VERSION OF BMI2 INTERVENTION IN PEDIATRIC CLINICS (18 INTERVENTION, 18 USUAL CARE WITH ATTENTION CONTROL, = 10,800 CHILDREN). THE CLINICS SERVE OVER 45,000 CHILDREN AGED 2-8 YRS WHO ARE OVERWEIGHT OR OBESE WITH HIGH RACIAL/ETHNIC AND SOCIOECONOMIC DIVERSITY (53% HISPANIC; 23% STATE- SUBSIDIZED INSURANCE). USING MI TECHNIQUES, PCPS WILL INITIATE AND MAINTAIN DISCUSSION ABOUT WEIGHT MANAGEMENT WITH PARENT (6 X 20 MIN) AND REFER PATIENTS ELECTRONICALLY TO EXPERIENCED AND MI-TRAINED LIFESTYLE COACHES. WITH FULL ACCESS TO THE EMR, COACHES WILL CALL REFERRED FAMILIES (CHILD’S BMI-FOR-AGE =85TH PERCENTILE) AND DELIVER INTERVENTION VIA TELEPHONIC MI COUNSELING OVER TWO YEARS (6 X 45 MIN). USUAL CARE CLINICS WITH ATTENTION CONTROL WILL INCLUDE REGULAR ENCOUNTERS AND EDUCATIONAL VIDEOS AS ATTENTION CONTROL. PRIMARY AIM: DETERMINE THE EFFECTIVENESS AND DOSE-RESPONSE RELATIONSHIP OF A PRAGMATIC, SYSTEM-INTEGRATED CHILDHOOD OBESITY INTERVENTION USING MBMI2KIDS (A MODIFIED BMI2 APPROACH) ON BMI AT 2-YR FOLLOW-UP. SECONDARY AIM: INVESTIGATE HOW PATIENT CHARACTERISTICS SUCH AS MINORITY OR LOW-INCOME BACKGROUND AND PARENTAL OBESITY MODIFY THE EFFECT OF THE MBMI2KIDS INTERVENTION (HETEROGENEITY OF EFFECTS). IMPACT: THIS STUDY HAS THE POTENTIAL FOR A HIGHLY SIGNIFICANT SHIFT IN PEDIATRIC PRIMARY CARE PRACTICES. OUR RESULTS WILL PROVIDE VALUABLE GUIDANCE TO PROVIDERS AND HEALTH CARE SYSTEMS TO HELP THEM EFFECTIVELY HALT AND REVERSE THE CHILDHOOD OBESITY EPIDEMIC. OUR RESULTS CAN BE QUICKLY TRANSLATED INTO OTHER CLINICAL CARE SETTINGS AND ENDORSE THE MEANINGFUL USE OF EMR SYSTEMS TO SUPPORT PROVIDERS USING TOOLS AND CENTRALIZED APPROACHES THAT MAKE INTERVENTIONS SCALABLE.

MHEALTH MINDFULNESS INTERVENTION FOR PREGNANT BLACK AND LATINA WOMEN AT RISK OF POSTPARTUM DEPRESSION - ABSTRACT POSTPARTUM DEPRESSION (PPD) IS A DEBILITATING AND COSTLY CONDITION AFFECTING OVER 20% OF POSTPARTUM WOMEN AND DISPROPORTIONATELY IMPACTS BLACKS AND LATINAS. THE COVID-19 PANDEMIC IS LEADING TO A SEVERE INCREASE IN THE RATE OF DEPRESSION WHILE THE US IS ALREADY STRUGGLING WITH DEEP-SEATED INEQUITIES IN MENTAL HEALTH CARE FOR BLACK AND LATINA POPULATIONS. THE US PREVENTIVE SERVICES TASK FORCE RECENTLY RECOMMENDED THAT WOMEN AT INCREASED RISK OF PPD SHOULD BE REFERRED FOR COUNSELING TO REDUCE THE RISK OF PPD. HOWEVER, NUMEROUS PATIENT- LEVEL (E.G. LACK OF TIME OR MONEY) AND SYSTEM-LEVEL BARRIERS (E.G. SHORTAGE OF PROVIDERS), NOW COMPOUNDED WITH THE COVID-19 PANDEMIC, POSE CHALLENGES TO THE RECEIPT OF COUNSELING, PARTICULARLY AMONG BLACK AND LATINA POPULATIONS THAT ALREADY EXPERIENCED A LOWER RATE OF TREATMENT INITIATION. THERE IS AN URGENT NEED FOR EVIDENCE- BASED ACCESSIBLE AND SCALABLE MENTAL HEALTH CARE OPTIONS FOR THESE HIGH-RISK AND VULNERABLE WOMEN. MINDFULNESS-BASED INTERVENTIONS (MBIS) ARE EFFECTIVE AND THEORY-DRIVEN INTERVENTIONS FOR REDUCING DEPRESSION SYMPTOMS. HOWEVER, STANDARD MBIS REQUIRE 30+ HOURS OF IN-PERSON OR ONLINE SESSIONS FOR 8 WEEKS AND ARE OFTEN TOO INTENSE FOR PREGNANT WOMEN WITH HIGH DEPRESSION SYMPTOM BURDEN. OUR PILOT STUDY OF A SELF-PACED, SMALL DOSAGE (10-20 MINUTES/DAY FOR 6 WEEKS), MOBILE-BASED (MHEALTH) MBI FOR PREGNANT WOMEN WITH HIGH DEPRESSION SYMPTOMS DEMONSTRATED PROMISING FEASIBILITY AND PRELIMINARY EFFICACY RESULTS IN REDUCING DEPRESSION SYMPTOMS PROVIDING SUPPORT FOR A FULLY-POWERED TRIAL. WE WILL CONDUCT A HYBRID EFFECTIVENESS- IMPLEMENTATION STUDY TO TEST THE EFFECTIVENESS OF THE MHEALTH MBI TO REDUCE POSTPARTUM DEPRESSION SYMPTOMS IN BLACK AND LATINA PREGNANT WOMEN AT INCREASED RISK OF PPD, AND EXAMINE BARRIERS AND FACILITATORS OF IMPLEMENTATION WITHIN A LARGE HEALTHCARE SYSTEM. THE STUDY WILL TAKE PLACE AT KAISER PERMANENTE NORTHERN CALIFORNIA (KPNC), AN INTEGRATED HEALTH CARE DELIVERY SYSTEM WITH A DIVERSE POPULATION AND COMPREHENSIVE ELECTRONIC HEALTH RECORDS. KPNC’S UNIVERSAL PERINATAL DEPRESSION SCREENING PROGRAM WILL BE LEVERAGED TO EFFICIENTLY IDENTIFY ELIGIBLE WOMEN. WE WILL RANDOMIZE 600 PREGNANT (300 LATINA AND 300 BLACK) WOMEN INTO THE INTERVENTION ARM OR TIME- AND ATTENTION-MATCHED CONTROL ARM AND ASK THEM TO PRACTICE MINDFULNESS OR ANOTHER PROGRAM FOR 6 WEEKS, 10-20 MINUTES A DAY. WE WILL PARTNER WITH HEADSPACETM AND TAILOR THE DIGITAL PLATFORM TO DELIVER THE MINDFULNESS PROGRAM AND OBTAIN ADHERENCE DATA. PATIENT-REPORTED OUTCOMES OF DEPRESSION (PRIMARY OUTCOME), ANXIETY, STRESS AND SLEEP (SECONDARY OUTCOMES), AND ATTENTION MONITORING AND ACCEPTANCE (TARGET ENGAGEMENTS) WILL BE COLLECTED 3 TIMES DURING THE STUDY (BASELINE, POST INTERVENTION, AND 4 WEEKS POSTPARTUM). IMPLEMENTATION OF THE INTERVENTION WILL BE EVALUATED USING THE RE-AIM FRAMEWORK (REACH, EFFECTIVENESS, ADOPTION, IMPLEMENTATION AND MAINTENANCE). FURTHER, USING THE RESULTS OF THIS TRIAL, WE WILL DETERMINE OPTIMAL DOSAGE AND TAILOR THE DIGITAL INTERVENTION. FINDINGS FROM THE IMPLEMENTATION EVALUATION WILL BE HIGHLY APPLICABLE TO SYSTEMS THAT ARE PLANNING TO INCORPORATE SELF-PACED MHEALTH MINDFULNESS INTERVENTIONS.

THE KAISER PERMANENTE NATIONAL RESEARCH DATABASE

EVALUATING EFFECTIVENESS AND IMPLEMENTATION OF A RISK MODEL FOR SUICIDE PREVENTION ACROSS HEALTH SYSTEMS - PROJECT SUMMARY/ABSTRACT: SUICIDE IS A MAJOR PUBLIC HEALTH CONCERN IN THE UNITED STATES; NEARLY 50,000 INDIVIDUALS DIE BY SUICIDE ANNUALLY AND ALMOST 1.5 MILLION ATTEMPT SUICIDE. TO DATE, IDENTIFICATION OF INDIVIDUALS AT RISK FOR SUICIDE HAS RELIED ON SUICIDE RISK SCREENING PRACTICES, INCLUDING USING A VARIETY OF SELF- REPORT INSTRUMENTS. HOWEVER, SENSITIVITY OF THESE MEASURES ARE ONLY MODERATE; MORE PRECISE TOOLS FOR IDENTIFYING PATIENTS AT RISK FOR SUICIDE ARE NEEDED. SUICIDE RISK MODELS, DEVELOPED BY OUR TEAM, INCORPORATE HEALTH RECORDS DATA AND HISTORICAL SELF-REPORT SCREENING QUESTIONNAIRE RESPONSES TO IMPROVE ACCURACY OF RISK PREDICTION. OUR MODELS HAVE OUTPERFORMED TRADITIONAL CLINICAL SCREENING AND SIMILAR RISK MODELS FOR ADULTS RECEIVING CARE IN OUTPATIENT MENTAL HEALTH SPECIALTY SETTINGS. HOWEVER, WHILE ACCURATE, THEY HAVE NOT BEEN EVALUATED IN REAL WORLD CARE; WHETHER THE MODELS ACTUALLY INCREASE IDENTIFICATION OR RESULT IN PATIENTS RECEIVING MORE SUICIDE PREVENTION SERVICES, FEWER CRISIS SERVICES, OR MAKING FEWER SUICIDE ATTEMPTS IS UNKNOWN. THERE IS SUBSTANTIAL CLINICAL INTEREST IN IMPLEMENTING SUICIDE RISK MODELS BUT LITTLE SCIENTIFIC EVIDENCE ABOUT THE EFFECTIVENESS OF THESE MODELS IN REAL WORLD SETTINGS COMPARED TO STANDARD SCREENING PRACTICES ALONE. ADDITIONALLY, THERE IS ALMOST NO GUIDANCE FOR THEIR IMPLEMENTATION IN HEALTHCARE. THE PROPOSED PROJECT LEVERAGES THE NIMH-FUNDED MENTAL HEALTH RESEARCH NETWORK (MHRN), A COLLABORATION OF LARGE HEALTH SYSTEMS WITH ESTABLISHED CLINICAL DATA INFRASTRUCTURE TO SUPPORT MULTI-SITE STUDIES. MHRN MEMBERS HENRY FORD HEALTH SYSTEM, KAISER PERMANENTE NORTHWEST, AND HEALTHPARTNERS WILL PARTICIPATE IN THIS PROJECT AND COLLECTIVELY SERVE >170,000 BEHAVIORAL HEALTH PATIENTS PER YEAR. THE PATIENT POPULATIONS ARE DIVERSE, INCLUDING THOUSANDS OF INDIVIDUALS WITH MEDICAID AND MEDICARE. EACH OF THESE SYSTEMS HAS IMPLEMENTED A SUICIDE PREVENTION CARE MODEL IN THEIR BEHAVIORAL HEALTH DEPARTMENTS, INCLUDING ROBUST SUICIDE RISK SCREENING AND ASSESSMENT PROCESSES. HOWEVER, NONE OF THESE SYSTEMS HAS IMPLEMENTED A SUICIDE RISK MODEL. THE PROPOSED PROJECT INCLUDES A PRAGMATIC TRIAL APPROACH WITH RANDOMIZATION OF BEHAVIORAL HEALTH CLINICS ACROSS THE THREE PARTICIPATING HEALTH SYSTEMS. IT IS INNOVATIVE BECAUSE IT SEEKS TO IMPLEMENT AN MHRN SUICIDE RISK MODEL (INTERVENTION) INTO EACH SYSTEM'S EXISTING SUICIDE PREVENTION CARE MODEL (USUAL CARE) TO INCREASE THE REACH AND EFFECTIVENESS OF THE SUICIDE PREVENTION CARE MODELS. SITES WILL RECEIVE IMPLEMENTATION PLANNING SUPPORT BASED ON STAKEHOLDER FEEDBACK FROM PRELIMINARY STUDIES AND DELIVERABLES INCLUDE AN IMPLEMENTATION PLANNING TOOL KIT TO FACILITATE SPREAD. THIS HIGH-IMPACT STUDY HAS IMPORTANT CLINICAL IMPLICATIONS AS HEALTH SYSTEMS CONSIDER WHETHER IT MAKES SENSE TO ENHANCE THEIR EXISTING SUICIDE PREVENTION CARE MODELS WITH A SUICIDE RISK MODEL. IT IS TIMELY BECAUSE MANY HEALTH SYSTEMS ARE ADVANCING TOWARD SUICIDE RISK MODEL IMPLEMENTATION WITHOUT EVIDENCE TO SUPPORT THIS INNOVATION.

INTERVENTION BASED IN PRIMARY CARE TO INCREASE PHYSICAL ACTIVITY AMONG INACTIVE ADULTS WITH PREDIABETES AND DIABETES

MULTILEVEL INTERVENTIONS TO INCREASE ADHERENCE TO LUNG CANCER SCREENING - ABSTRACT SCREENING FOR LUNG CANCER HAS THE POTENTIAL FOR A PROFOUND PUBLIC HEALTH BENEFIT. LUNG CANCER IS THE LEADING CAUSE OF US CANCER MORBIDITY AND MORTALITY FOR BOTH MEN AND WOMEN, RESPONSIBLE FOR MORE DEATHS THAN BREAST, CERVICAL, COLORECTAL, AND PROSTATE CANCERS COMBINED. ANNUAL SCREENING WITH LOW-DOSE COMPUTED TOMOGRAPHY (LDCT) REDUCED LUNG CANCER MORTALITY BY 20%. SUCCESSFUL POPULATION-BASED SCREENING REQUIRES CONTINUOUS MONITORING TO ADHERENCE REPEAT SCREENING IN HIGH RISK ADULTS TO ACHIEVE SIMILAR RESULTS. REPEAT ANNUAL SCREENING IS NECESSARY FOR EARLY DETECTION OF LUNG CANCER. BASELINE OR FIRST LDCT SCANS DETECT PREVALENT LUNG CANCER, WHEN SUBSEQUENT SCREENING DETECTS NEW NODULES. HOWEVER, ADHERENCE TO SCREENING IS LOW, RANGING AT 28-38% FROM CENTERS NATIONALLY. MULTILEVEL INTERVENTIONS, WHICH TARGET PATIENTS, CLINICIANS, AND HEALTHCARE SYSTEMS, OFFER A PROMISING FRAMEWORK TO ADDRESS THE GAPS IN LUNG CANCER SCREENING TO ACHIEVE GUIDELINE- RECOMMENDED LUNG CANCER SCREENING. OUR MIXED-METHODS PILOT STUDY WITH KPWA STAKEHOLDERS TWO CRITICAL COMPONENTS TO IMPROVE ADHERENCE TO REPEAT SCREENING: PROVIDING EDUCATION FOR PATIENTS ON LUNG CANCER SCREENING, AND OFFERING REMINDERS FOR ON-TIME RETURN TO SCREENING. WE DEVELOPED TWO NOVEL PATIENT-CENTERED INTERVENTIONS USING PRINCIPLES OF HUMAN-CENTERED DESIGN TO ADDRESS THESE NEEDS: 1) PATIENT VOICES VIDEO THAT INCORPORATES PATIENT TESTIMONIALS TO ACKNOWLEDGE RECEIPT OF SCREENING, A TAILORED REMINDER OF TIME DUE FOR NEXT SCAN, AND REASSURANCE TO REDUCE FEAR OF SCREENING AND ROLE OF LOVED ONES TO SUPPORT HEALTH CHOICES; AND 2) STEPPED REMINDERS, THAT DIRECTLY REMINDS PATIENTS WHEN THEIR NEXT SCAN IS DUE. BOTH INTERVENTIONS ARE FACILITATED BY A HEALTH SYSTEM ELECTRONIC HEALTH RECORD (EHR) BUILD TO TRACK PATIENTS FOR POPULATION HEALTH MANAGEMENT AND A CLINICALLY-EMBEDDED MEDICAL ASSISTANT TO DELIVER INTERVENTIONS. THE GOAL OF THIS PROPOSAL IS TO TEST THESE TWO INTERVENTIONS RELATIVE TO USUAL CARE TO PROMOTE ADHERENCE TO REPEAT SCREENING IN A PRAGMATIC CLUSTER RANDOMIZED TRIAL ENROLLING 1775 ADULT KPWA MEMBERS, WHO COMPLETE A SCREENING LDCT IN 2022-2025 ACROSS 34 KPWA PRIMARY CARE CLINICS IN A 2X2 FACTORIAL-DESIGNED STUDY. STUDY ARMS INCLUDE: A) STEPPED REMINDERS ALONE; B) PATIENT VOICES VIDEO ALONE; C) BOTH INTERVENTIONS; OR D) USUAL CARE. TO ADDRESS OUR GOALS, OUR SPECIFIC AIMS ARE TO: 1) COMPARE EFFECTIVENESS OF TWO MULTILEVEL INTERVENTIONS RELATIVE TO USUAL CARE IN IMPROVING (A) RATES OF ADHERENCE TO LUNG CANCER SCREENING, (B) PATIENT-CENTERED OUTCOMES; AND (C) CLINIC OUTCOMES; AND 2) DETERMINE THE PATIENT-, CLINICIAN-, AND SYSTEM-LEVEL FACTORS THAT INFLUENCE CHANGES IN ADHERENCE TO INFORM LUNG CANCER SCREENING PROGRAMS. TO DATE, NO RANDOMIZED CLINICAL TRIAL HAS EVALUATED STRATEGIES TO IMPROVE ADHERENCE TO LUNG CANCER SCREENING IN US POPULATIONS WITH MULTILEVEL STRATEGIES. WE WILL MOVE THE FIELD FORWARD BY PROVIDING EFFECTIVE, SCALABLE INTERVENTIONS TO IMPROVE LUNG CANCER SCREENING ADHERENCE TO ACHIEVE THE POPULATION-BASED MORTALITY BENEFITS PROMISED BY LARGE CLINICAL TRIALS THAT MOTIVATED SCREENING GUIDELINES.

THE IMPACT OF AIR POLLUTION EXPOSURE ON COVID-19 SEVERITY AND MORTALITY

ASSESSING THE IMPACT OF CANNABIS LEGALIZATION ON ADOLESCENT CANNABIS USE AND CANNABIS-RELATED HEALTH CONDITIONS - PROJECT SUMMARY/ABSTRACT ADOLESCENT CANNABIS USE IS INCREASINGLY RECOGNIZED AS AN IMPORTANT PUBLIC HEALTH PROBLEM WITH SIGNIFICANT ADVERSE HEALTH CONSEQUENCES. RECREATIONAL CANNABIS LEGALIZATION (RCL) HAS HIGH POTENTIAL TO INCREASE RISK FOR ADOLESCENT CANNABIS USE AND CANNABIS-RELATED HEALTH CONDITIONS. HOWEVER, THE EFFECTS OF RCL ON ADOLESCENTS ARE UNKNOWN. WITH A HIGHLY REPRESENTATIVE SAMPLE OF NEARLY 1 MILLION ADOLESCENTS (N=900,000) REGULARLY SCREENED FOR CANNABIS USE IN KAISER PERMANENTE NORTHERN CALIFORNIA’S LARGE INTEGRATED HEALTHCARE DELIVERY SYSTEM FROM 2015 TO 2023, THIS MULTI-METHOD STUDY WILL ADDRESS THE PRESSING PUBLIC HEALTH QUESTIONS OF WHETHER AND HOW CALIFORNIA STATE RCL AND HETEROGENEITY OF LOCAL REGULATORY SCHEMES IMPACT THE RISK OF ADOLESCENT CANNABIS USE AND CANNABIS-RELATED HEALTH CONDITIONS. WE WILL USE A QUASI-EXPERIMENTAL INTERRUPTED TIME SERIES DESIGN TO TEST WHETHER ADOLESCENT CANNABIS USE, CANNABIS-RELATED HEALTH CONDITIONS (E.G., CANNABIS USE DISORDER, OTHER SUBSTANCE USE, RESPIRATORY SYMPTOMS, MENTAL HEALTH PROBLEMS, CANNABIS-RELATED ACCIDENTS, ACUTE CANNABIS INTOXICATION, CANNABINOID HYPEREMESIS SYNDROME), AND CANNABIS-RELATED HEALTHCARE USE (E.G., EMERGENCY DEPARTMENT, ADDICTION TREATMENT) AND RISE POST-RCL. WE WILL ALSO EXAMINE LOCAL RCL POLICIES (RETAILER BANS OR CAPS, PRODUCT AND ADVERTISING RESTRICTIONS, TAXES, HEALTH WARNINGS) AND USE GEOGRAPHIC INFORMATION SYSTEMS METHODS TO MAP RETAILER LOCATION (E.G., DISTANCE FROM HOME ADDRESS TO THE CLOSEST RETAILER) ONTO INDIVIDUAL-LEVEL ELECTRONIC HEALTH RECORD DATA COLLECTED IN CLINICAL CARE TO TEST WHETHER THE EFFECTS OF RCL ARE STRONGER AMONG THOSE WHO LIVE IN COMMUNITIES WITH LESS RESTRICTIVE LOCAL POLICIES, ADJUSTING FOR PRE-RCL MEDICAL CANNABIS POLICIES. WE WILL CONDUCT HYPOTHESIS-DRIVEN MODERATION ANALYSES TO IDENTIFY SUB-GROUPS WHOSE RISK FOR CANNABIS USE AND CANNABIS-RELATED HEALTH CONDITIONS MAY BE GREATEST FOLLOWING RCL. TO GAIN FURTHER CLINICAL INSIGHT INTO OUR QUANTITATIVE DATA AND GUIDE NEXT STEPS, WE WILL CONDUCT FOCUS GROUPS WITH ADOLESCENTS AND INTERVIEWS WITH ADDICTION MEDICINE CLINICIANS, PEDIATRICIANS, AND EMERGENCY DEPARTMENT PHYSICIANS TO GAIN INSIGHT INTO HOW RCL IMPACTS ADOLESCENT CANNABIS USE AND ADDICTION TREATMENT NEED FROM THE PERSPECTIVE OF BOTH PATIENTS AND PROVIDERS. TOGETHER, RESULTS WILL HAVE IMMEDIATE PUBLIC HEALTH AND CLINICAL IMPLICATIONS, PROVIDING URGENTLY NEEDED DATA TO IDENTIFY POTENTIALLY ACTIONABLE AREAS FOR FUTURE POLICY ADAPTATIONS AND AID DECISION MAKING FOR PUBLIC HEALTH PRACTICES TO REDUCE ADOLESCENT CANNABIS USE AND CANNABIS-RELATED HARMS.

HEALTH AND ECONOMIC EFFECTS OF LIGHT RAIL LINES: A NATURAL EXPERIMENT

PARK, RX, PHYSICAL ACTIVITY AND OTHER HEALTH BENEFITS FOR LOW INCOME CHILDREN

USING PEER SUPPORT TO AID IN PREVENTION AND TREATMENT IN PREDIABETES (UPSTART)

PRENATAL BLOOD PRESSURE PATTERNS TO PREDICT PREGNANCY-RELATED HYPERTENSION AND LATER LIFE CARDIOVASCULAR RISK

COMPARING THE EFFECTS OF PRENATAL DEPRESSION AND ITS TREATMENT ON DEVELOPMENTAL OUTCOMES OF THE OFFSPRING

VENOUS THROMBOEMBOLISM SEQUELAE IN A POPULATION-BASED INCEPTION COHORT - PROJECT SUMMARY / ABSTRACT NEARLY 1 MILLION AMERICANS EACH YEAR EXPERIENCE A FIRST VENOUS THROMBOEMBOLISM (VTE), WHICH INCLUDES DEEP VEIN THROMBOSIS (DVT) AND PULMONARY EMBOLISM (PE). VTE IS TYPICALLY VIEWED AS AN ACUTE EVENT THAT IS TREATABLE BY ANTICOAGULANTS, WITH LESS FOCUS ON CHRONIC ADVERSE VTE SEQUELAE OR ON REHABILITATION. ADULTS WHO HAVE EXPERIENCED AN INCIDENT VTE MAY BE AT HIGH RISK FOR ADVERSE VTE SEQUELAE IN THE FIRST 12 MONTHS AFTER THEIR EVENT, INCLUDING PATIENT-RELEVANT SYMPTOMS (SUCH AS DYSPNEA, PAIN, AND SWELLING) AND ADVERSE CLINICAL OUTCOMES (VTE RECURRENCE AND DEATH). RESEARCH TO-DATE HAS CHARACTERIZED THE POST-THROMBOTIC SYNDROME OCCURRING POST-DVT, BUT THERE HAS BEEN MUCH LESS ATTENTION GIVEN TO SEQUELAE FOLLOWING AN INCIDENT PE. FURTHERMORE, ALMOST ALL RESEARCH ABOUT SEQUELAE AFTER BOTH DVT AND PE HAS BEEN IN THE CONTEXT OF ANTICOAGULATION WITH VITAMIN K ANTAGONISTS RATHER THAN WITH NEWER DIRECT ORAL ANTICOAGULANTS (DOACS), WHICH ARE NOW PRIMARILY USED IN PRACTICE. CLINICALLY, WE LACK METHODS TO IDENTIFY ADULTS AT GREATEST RISK OF ADVERSE VTE SEQUELAE AND HOW TO PREVENT THESE SEQUELAE. WHETHER SEVERAL PROMISING BIOMARKERS THAT ARE READILY AVAILABLE FOR CLINICAL MEASUREMENT (BRAIN NATRIURETIC PEPTIDE, D-DIMER, AND TROPONIN), OR, WHETHER MODIFIABLE EXPOSURES SUCH AS ANTICOAGULANT TYPE OR PHYSICAL ACTIVITY ARE ASSOCIATED WITH ADVERSE VTE SEQUELAE IS INCOMPLETELY UNDERSTOOD. IN THE PROPOSED RESEARCH, WE WILL CHARACTERIZE PATIENT-RELEVANT SYMPTOMS AND ADVERSE CLINICAL OUTCOMES AT MULTIPLE TIMEPOINTS IN THE FIRST 12 MONTHS POST-VTE AND WILL EVALUATE BIOMARKERS AND MODIFIABLE RISK FACTORS IN RELATION TO THESE VTE SEQUELAE. TO ACCOMPLISH THIS, WE WILL CREATE A NEW PROSPECTIVE POPULATION- BASED INCEPTION COHORT STUDY BASED IN KAISER PERMANENTE WASHINGTON, AN INTEGRATED HEALTHCARE DELIVERY SYSTEM IN WASHINGTON STATE. OUR PRELIMINARY RESEARCH SUPPORTS THE FEASIBILITY OF DAILY IDENTIFICATION OF INCIDENT VTE CASES AMONG ADULT ENROLLEES, AND WE ANTICIPATE ~957 ELIGIBLE ADULTS WITH VALIDATED VTE ACROSS 33 MONTHS OF ENROLLMENT. DE NOVO DATA COLLECTION IN ~380 CONSENTING ADULTS WILL INCLUDE: 1) SURVEYS AT 2 WEEKS AND 1, 3, 6, AND 12 MONTHS POST-VTE TO COLLECT INFORMATION ON POST-VTE SYMPTOMS, 2) WRIST-WORN ACCELEROMETERS TO OBJECTIVELY MEASURE PHYSICAL ACTIVITY AND RESTING HEART RATE IN THE 12 MONTHS POST-VTE, AND 3) BLOOD COLLECTION WITHIN 4 WEEKS OF THE INCIDENT VTE TO MEASURE 3 PRE-SPECIFIED BIOMARKERS. THESE STUDY DATA WILL BE COMBINED WITH RICH ELECTRONIC HEALTH RECORD DATA TO ACCOMPLISH 3 SCIENTIFIC AIMS: (1) CHARACTERIZE THE PREVALENCE PATTERN OF SYMPTOMS AT 2 WEEKS AND 1, 3, 6, AND 12 MONTHS POST-INCIDENT VTE AND CLINICAL OUTCOMES OVER THE 12 MONTHS OF FOLLOW-UP; (2) EVALUATE THE ASSOCIATIONS OF KEY BIOMARKER LEVELS MEASURED IN BLOOD COLLECTED WITHIN 4 WEEKS OF THE INCIDENT VTE; AND, (3) EVALUATE MODIFIABLE RISK FACTORS FOR SEQUALAE, INCLUDING VTE ANTICOAGULANT TYPE AND PHYSICAL ACTIVITY LEVEL. THIS RESEARCH WILL FILL CRITICAL KNOWLEDGE GAPS THAT ARE IMPORTANT TO PATIENTS BY PROVIDING ESTIMATES OF THE PREVALENCE OF CLINICALLY BURDENSOME VTE SEQUELAE AND IDENTIFYING POSSIBLE ETIOLOGIC AND MODIFIABLE RISK FACTORS THAT CAN BE TARGETED IN FUTURE INTERVENTIONS.

SOCIAL NETWORKS AND DISPARITIES IN HEALTH BEHAVIORS AND BREAST CANCER OUTCOMES IN IMMIGRANT WOMEN

RANDOMIZED TRIAL TO REDUCE SITTING TIME AND IMPROVE CARDIOMETABOLIC HEALTH IN OBESE OLDER ADULTS

LONG TERM ADVERSE HEALTH OUTCOMES FOR WOMEN AND CHILDREN FOLLOWING SARS-COV-2 INFECTION DURING PREGNANCY - PROJECT SUMMARY SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) INFECTION, THE VIRUS RESPONSIBLE FOR THE GLOBAL COVID-19 PANDEMIC OF UNPRECEDENTED SCALE CAUSES A MULTI-ORGAN DISEASE WITH WIDESPREAD EFFECTS. INCREASING EVIDENCE SUGGESTS LONG-TERM EFFECTS OF SARS-COV-2 INFECTION IN SOME INDIVIDUALS PRESENT UP TO A YEAR AFTER INITIAL INFECTION, REFERRED TO AS POST-ACUTE SEQUELAE OF SARS-COV-2 (PASC). PREGNANT WOMEN AND THEIR FETUSES MAY BE PARTICULARLY VULNERABLE TO THE LONG-TERM EFFECTS OF SARS-COV-2 INFECTION. THE BIOLOGICAL PLAUSIBILITY AND EMERGING EPIDEMIOLOGICAL EVIDENCE FROM SARS-COV-2 INFECTIONS IN THE POPULATION HIGHLIGHT THE URGENT NEED FOR RESEARCH ON THE LONG-TERM EFFECTS OF SARS-COV-2 INFECTION DURING PREGNANCY ON WOMEN’S CARDIOMETABOLIC AND NEUROPSYCHIATRIC HEALTH OUTCOMES AND CHILDREN’S GROWTH AND DEVELOPMENT. LIMITATIONS OF CURRENT STUDIES OF BOTH PREGNANT WOMEN WITH SARS-COV-2 INFECTION AND THEIR CHILDREN EXPOSED IN UTERO, INCLUDE A LACK OF LONG-TERM FOLLOW-UP, LACK OF DATA ON PRE-EXISTING CONDITIONS MAKING IT DIFFICULT TO DISENTANGLE RISK FACTORS FOR THE INFECTION FROM ITS CONSEQUENCES, AND LIMITED ABILITY TO EXAMINE ASSOCIATIONS BY PREDOMINANT SARS-COV-2 VARIANT AND VACCINATION STATUS. THE PROPOSED STUDY LEVERAGES KAISER PERMANENTE NORTHERN CALIFORNIA’S (KPNC’S) HIGH-QUALITY ELECTRONIC HEALTH RECORDS (EHR) DATA ON SARS-COV-2 INFECTION TESTING AND RESULTS TO ASSEMBLE A LONGITUDINAL PREGNANCY COHORT OF >195,000 PREGNANT WOMEN (>22,000 WOMEN WITH SARS-COV-2 INFECTION DURING PREGNANCY AND APPROXIMATELY>173,000 WITHOUT) BETWEEN MARCH 2020 AND DECEMBER 2022. WE WILL USE OUR ROBUST AND COMPREHENSIVE EHR TO FOLLOW WOMEN AND THEIR CHILDREN FOR UP TO 5 YEARS AND ASCERTAIN CLINICAL DIAGNOSES DATA. ADDITIONALLY, WE WILL RECRUIT AND SURVEY A SUBSAMPLE OF 2000 OF THE MOTHER-CHILD DYADS WHEN THE CHILD IS 3 YEARS OLD TO ASCERTAIN WOMEN’S AND CHILDREN’S SELF/PARENT-REPORTED SUBCLINICAL HEALTH OUTCOMES NOT AVAILABLE IN THE EHR, BUT THAT MAY SUGGEST A NEED TO MONITOR AND/OR PROVIDE EARLY INTERVENTIONS. WE WILL RANDOMLY IDENTIFY 1000 DYADS WITH SARS-COV-2 INFECTION DURING PREGNANCY (1/3 EARLY VARIANTS, 1/3 DELTA AND 1/3 OMICRON VARIANTS) AND 1000 DYADS WITHOUT SARS-COV-2 INFECTION DURING PREGNANCY. OUR STUDY WILL ASSESS THE FOLLOWING: 1) EVALUATE THE LONG-TERM EFFECTS OF A SARS-COV-2 INFECTION DURING PREGNANCY ON WOMEN’S CARDIOMETABOLIC AND NEUROPSYCHIATRIC OUTCOMES (EHR AND SELF-REPORT), AND 2) EVALUATE THE LONG-TERM EFFECTS OF IN UTERO EXPOSURE TO SARS-COV-2 INFECTION ON CHILD GROWTH TRAJECTORY AND NEURODEVELOPMENT (EHR AND PARENT-REPORT). WE WILL EXAMINE VARIANT, SEVERITY OF INFECTION AND GESTATIONAL AGE AT INFECTION IN RELATION TO ALL OUTCOMES OF INTEREST AND EXPLORE EFFECT MODIFICATION BY VACCINATION STATUS, RACE/ETHNICITY AND PRE-EXISTING CO-MORBIDITIES. FINALLY, OUR ANALYSES WILL INCLUDE INFECTION STATUS BEFORE, DURING AND AFTER PREGNANCY OR BIRTH ALLOWING FOR ESTIMATION OF JOINT EFFECTS. THIS PROJECT WILL FILL A SIGNIFICANT GAP INFORMING WOMEN AND CHILDREN EXPOSED TO SARS-COV-2 INFECTION DURING PREGNANCY, THE PUBLIC, CLINICIANS, AND HEALTH CARE SYSTEMS OF THE FULL SPECTRUM OF HEALTH CONSEQUENCES OF INFECTION.

OPTIMIZING MEDICAL DECISION MAKING FOR OLDER PATIENTS WITH TYPE 2 DIABETES

MULTI-ETHNIC MULTI-CANCER EARLY DETECTION AND SCREENING (MED SCREEN) STUDY - PROJECT SUMMARY MULTI-CANCER DETECTION (MCD) TESTS, WHICH EVALUATE CELL-FREE DNA AND OTHER BIOLOGICAL COMPONENTS WITH A SINGLE BLOOD DRAW, ARE A NEW FRONTIER IN CANCER SCREENING, PARTICULARLY FOR CANCERS WITH NO EFFECTIVE SCREENING METHODS. DESPITE COMMERCIAL AVAILABILITY, LITTLE IS KNOWN ABOUT THEIR FEASIBILITY, ACCEPTABILITY, AND EFFECTIVENESS ACROSS DIVERSE SETTINGS AND POPULATIONS. TO ADDRESS THIS EVIDENCE GAP, THE NATIONAL CANCER INSTITUTE (NCI) IS CREATING THE CANCER SCREENING RESEARCH NETWORK (CSRN) TO CONDUCT RIGOROUS, MULTICENTER CANCER SCREENING STUDIES. IN RESPONSE TO RFA-CA-23-020, WE PROPOSE A CSRN ACCRUAL, ENROLLMENT, AND SCREENING SITE (ACCESS) HUB THAT WILL RECRUIT PARTICIPANTS FOR THE INITIAL VANGUARD STUDY FROM KAISER PERMANENTE (KP) ACROSS 21 SOCIODEMOGRAPHICALLY DIVERSE MEDICAL CENTERS IN URBAN, SUBURBAN, AND SEMI-RURAL AREAS OF CALIFORNIA THAT INCLUDE ~1.45 MILLION ADULTS AGES 45-70 YEARS AND THAT CAN EFFICIENTLY EXPAND, FOR FOLLOW-UP CSRN STUDIES, TO 36 MEDICAL CENTERS WITH ~3 MILLION SCREENING-ELIGIBLE ADULTS. OUR UNDERLYING POPULATION FOR THE VANGUARD STUDY INCLUDES LARGE NUMBERS OF ASIAN OR PACIFIC ISLANDER (311,959), BLACK (100,910), AND HISPANIC (285,287) ADULTS COVERED BY MEDICARE, MEDICAID, AND COMMERCIAL INSURANCE, ALLOWING FOR OVERSAMPLING AND INCLUSION OF UNDERREPRESENTED GROUPS. EFFICIENTLY LINKED BY ADMINISTRATIVE AND CLINICAL DATA SYSTEMS WITHIN AN INTEGRATED HEALTH CARE SYSTEM, THE KP ACCESS HUB IS WELL-SUITED TO ACHIEVE THE CSRN’S GOALS. OUR SETTING PROVIDES COMPREHENSIVE PRIMARY AND SPECIALTY CARE WITH CONTINUOUS LONGITUDINAL TRACKING OF HEALTHCARE UTILIZATION, INCLUDING STANDARD OF CARE CANCER SCREENING; HAS LOW LOSS TO FOLLOW-UP DUE TO HEALTH PLAN DISENROLLMENT; AND CAPTURES COMPLETE REAL-TIME INFORMATION ON PATIENT ENCOUNTERS, REFERRALS, DIAGNOSES, PROCEDURES, TEST RESULTS, TREATMENTS, AND OUTCOMES IN EXTENSIVE ELECTRONIC HEALTH RECORD DATA SYSTEMS, INCLUDING LABORATORY, PATHOLOGY, RADIOLOGY, AND CANCER REGISTRY DATABASES. THE KP ACCESS HUB WILL BE LED BY A MULTIDISCIPLINARY TEAM EMBEDDED WITHIN KP CLINICAL OPERATIONS AND RESEARCH STRUCTURES. THE TEAM HAS DECADES OF CLINICAL, SCIENTIFIC, AND IMPLEMENTATION EXPERTISE IN CANCER SCREENING AND PROVEN EXPERIENCE WITH RECRUITING PARTICIPANTS FOR LARGE-VOLUME TRIALS, DATA MANAGEMENT, AND SPECIMEN COLLECTION, INCLUDING THE USE OF OVERSAMPLING AND OTHER STRATEGIES FOR OPTIMIZING PARTICIPANT DIVERSITY AND ENGAGEMENT. DRAWING ON THESE COLLECTIVE STRENGTHS, OUR SPECIFIC AIMS ARE TO: (1) RECRUIT, ENROLL, RETAIN, AND FOLLOW A SOCIODEMOGRAPHICALLY DIVERSE SAMPLE OF 2,400 ASYMPTOMATIC, AVERAGE-RISK ADULTS AGES 45-70 YEARS, INCLUDING UNDERSTANDING BARRIERS TO PARTICIPATION FOR UNDERREPRESENTED GROUPS; (2) DEVELOP AND ASSESS PROCESSES TO EFFECTIVELY COMMUNICATE MCD TEST RESULTS TO PARTICIPANTS AND PROVIDERS; (3) IDENTIFY AND EVALUATE DIAGNOSTIC PATHWAYS FOLLOWING A POSITIVE MCD TEST FOR TIMELY FOLLOW-UP CARE; AND (4) COLLECT AND TRANSFER HIGH-QUALITY DATA AND SPECIMENS FROM STUDY RECRUITMENT THROUGH CLOSEOUT FOR ALL NEEDED ENDPOINTS. IN CLOSE COLLABORATION WITH THE COORDINATING AND COMMUNICATION CENTER, STATISTICS AND DATA MANAGEMENT CENTER, OTHER ACCESS HUBS, AND THE NCI, THE KP ACCESS HUB CAN INFORM THE EVALUATION OF MCD TESTS ACROSS DIVERSE POPULATIONS.

CHILDHOOD MALTREATMENT AND DISEASE RISK IN YOUNG ADULTHOOD: THE ROLE OF HPA REGULATION IN ADOLESCENCE - ABSTRACT CHILD MALTREATMENT IS A SIGNIFICANT AND COSTLY SOCIAL ISSUE WITH OVER 670,000 DOCUMENTED CASES ANNUALLY. THE EFFECTS OF MALTREATMENT ARE WIDE-RANGING AND INCLUDE INCREASED RATES OF MORBIDITY AND MORTALITY FROM CHRONIC DISEASES. TO IMPROVE THE HEALTH AND MORTALITY OF THIS VULNERABLE POPULATION IT IS CRITICAL TO DELINEATE THE PATHWAYS THROUGH WHICH MALTREATMENT CONTRIBUTES TO INCREASED RISK FOR DISEASE AND IDENTIFY OPPORTUNITIES FOR PREVENTION. DYSREGULATION OF THE BODY’S PHYSIOLOGICAL STRESS RESPONSE SYSTEMS CONSTITUTES A KEY PATHWAY THROUGH WHICH EARLY MALTREATMENT SHAPES BIOLOGICAL AGING PROCESSES AND RISK FOR SUBSEQUENT DISEASE. IN ADDITION, RECALIBRATION OF THE STRESS SYSTEM DURING ADOLESCENCE MAY MITIGATE THE EFFECTS OF EARLY TRAUMA ON DISEASE RISK. ALTHOUGH THE HPA AXIS IN PARTICULAR HAS BEEN IMPLICATED AS A KEY MECHANISM LINKING MALTREATMENT WITH DISEASE, THESE ASSOCIATIONS HAVE ONLY BEEN TESTED BETWEEN ANY TWO OF THESE VARIABLES (I.E., MALTREATMENT AND HPA AXIS FUNCTION, MALTREATMENT AND DISEASE, OR HPA AXIS FUNCTION AND DISEASE) USING CROSS-SECTIONAL OR RETROSPECTIVE REPORTS OF MALTREATMENT. THIS STUDY WILL BE THE FIRST TO TEST THIS HYPOTHESIZED MEDIATION MODEL FROM MALTREATMENT TO DISEASE RISK VIA HPA FUNCTIONING USING A DEVELOPMENTAL FRAMEWORK FROM CHILDHOOD TO YOUNG ADULTHOOD, INCORPORATING MULTIPLE INDICES OF DISEASE RISK. SECOND, THE PROPOSED WORK WILL BE THE FIRST TO USE INNOVATIVE NEW MODELING TECHNIQUES TO CHARACTERIZE HPA AXIS FUNCTIONING ACROSS FOUR TIMEPOINTS IN ADOLESCENCE TO PINPOINT THE PARTICULAR ASPECTS OF THE STRESS RESPONSE AND DEVELOPMENTAL PERIODS OF STRESS SYSTEM SENSITIVITY THAT MAY LEAD TO DISEASE RISK. FINALLY, THIS STUDY WILL MOVE BEYOND CURRENT CONCEPTUALIZATIONS OF STRESS SYSTEM DYSFUNCTION BY IDENTIFYING RESILIENT PROFILES OF HPA AXIS FUNCTIONING AND MODERATORS OF HPA AXIS RECALIBRATION THAT WILL PROVIDE CRITICAL NEW INSIGHTS FOR INTERVENTION EFFORTS FOCUSED ON MITIGATING THE EFFECTS OF MALTREATMENT ON DISEASE RISK. THE IMPORTANCE OF ASSESSING DISEASE RISK IN YOUNG ADULTHOOD IS BOLSTERED BY DATA INDICATING THIS PERIOD OF LIFE AS A POTENTIAL INFLECTION POINT FOR LONG-TERM DISEASE RISK. AS SUCH, YOUNG ADULTHOOD MAY BE A CRITICAL WINDOW FOR PREVENTION AND AN OPTIMAL TIME TO ASSESS MODIFIABLE HEALTH RISKS. TO ACCOMPLISH THIS, WE WILL LEVERAGE A UNIQUE PROSPECTIVE LONGITUDINAL DATASET INCLUDING YOUTH WITH DOCUMENTED MALTREATMENT HISTORIES AND A COMPARISON GROUP FROM THE SAME COMMUNITIES (90% MINORITY RACE/ETHNICITY). THIS EXEMPLARY DATASET WILL BE AUGMENTED WITH FOLLOW-UP ASSESSMENT IN YOUNG ADULTHOOD TO CAPTURE DISEASE RISK. THE FINDINGS WILL PROVIDE THE FIRST LONGITUDINAL EVIDENCE OF HPA AXIS AS A CRITICAL MECHANISM THROUGH WHICH CHILDHOOD MALTREATMENT CONTRIBUTES TO A LIFELONG TRAJECTORY OF DISEASE AND WHETHER RECALIBRATION OF THE HPA AXIS IN ADOLESCENCE CAN MITIGATE THE EFFECTS OF EARLY TRAUMA ON DISEASE RISK IN YOUNG ADULTHOOD. IDENTIFICATION OF SPECIFIC MODERATORS OF HPA AXIS RECALIBRATION CAN DIRECTLY INFORM INTERVENTION AND PREVENT STRESS-INDUCED DISEASE.

CHARTGLUCOSE4MOMS: CHARACTERIZING, BY TRIMESTER, CONTINUOUS GLUCOSE MONITORING MEASUREMENTS FOR DETERMINING EFFECTS ON MATERNAL & OFFSPRING METABOLIC SEQUELAE

IDENTIFYING AND ADDRESSING BIAS IN DEPRESSION AND ANXIETY QUALITY MEASURES - SUMMARY RFA MH-23-265 IDENTIFIES A CRUCIAL NEED FOR VALIDATED OUTCOME-FOCUSED QUALITY MEASURES TO INCENTIVIZE QUALITY IMPROVEMENT, INFORM CONSUMERS’ CHOICES REGARDING CARE PROVIDERS, AND MOTIVATE SYSTEMATIC ASSESSMENT OF OUTCOMES IN COMMUNITY PRACTICE. QUALITY MEASURES BASED IN PATIENT-REPORTED DEPRESSION OUTCOMES ARE NOW INCLUDED IN NATIONAL COMMITTEE FOR QUALITY ASSURANCE HEALTHCARE EFFECTIVENESS DATA AND INFORMATION SET (HEDIS) “REPORT CARDS” FOR HEALTHCARE SYSTEMS AND THE CENTER FOR MEDICARE AND MEDICAID SERVICES MERIT-BASED INCENTIVE PAYMENT SYSTEM (MIPS) PROGRAM TO ADJUST FEE-FOR-SERVICE MEDICARE PAYMENTS. SIMILAR MEASURES ARE PROPOSED TO ASSESS AND REWARD THE QUALITY OF ANXIETY TREATMENT. WHILE OUTCOME-BASED QUALITY MEASURES SHOULD REWARD MORE EFFECTIVE CARE, IMPLEMENTATION MUST GUARD AGAINST PERPETUATING OR EXACERBATING INEQUITIES. INCENTIVES INTENDED TO BE RACE-NEUTRAL, OR EVEN THOSE AIMING TO REDUCE DISPARITIES, CAN HAVE INEQUITABLE CONSEQUENCES, PENALIZING THOSE SERVING MORE BLACK AND HISPANIC PATIENTS. FOUR SPECIFIC ASPECTS OF EXISTING DEPRESSION MEASURES MAY EXACERBATE INEQUITIES: • BROAD DENOMINATOR DEFINITIONS, INCLUDING PATIENTS WITH WIDELY VARYING TREATMENT HISTORY AND PROGNOSIS • PREFERENCE FOR MEASURES OF REMISSION RATHER THAN PROPORTIONAL IMPROVEMENT OR RESPONSE • FOCUS ON RELATIVELY NARROW OUTCOME WINDOWS AS LATE AS 12 MONTHS AFTER INITIATING TREATMENT • CONSIDERING ALL OBSERVATIONS WITHOUT RECORDED OUTCOME SCORES TO BE TREATMENT FAILURES DATA REGARDING CURRENT DEPRESSION MEASURES BOTH DEMONSTRATE SUBSTANTIAL RACIAL AND ETHNIC DISPARITIES AND RAISE CONCERNS REGARDING SPECIFIC DESIGN DECISIONS THAT MAY REINFORCE OR EXACERBATE INEQUITIES. WHILE THESE BIASES COULD BE ADDRESSED BY DETAILED STANDARDIZATION OR ADJUSTMENT, BENEFITS OF MORE COMPLEX MEASURES MUST BE WEIGHED AGAINST THE VALUE OF SIMPLICITY AND TRANSPARENCY TO MEASUREMENT USERS. WE PROPOSE TO USE DATA FROM 5 LARGE HEALTH SYSTEMS, INCLUDING OVER 350,000 EPISODES OF CARE FOR DEPRESSION TO EVALUATE BIASES IN EXISTING AND PROPOSED OUTCOME-BASED QUALITY MEASURES. SPECIFIC AIMS INCLUDE: AIM 1 – IDENTIFY PATIENT CHARACTERISTICS THAT LEAD TO LOWER HEDIS/MIPS QUALITY SCORES FOR THOSE SERVING MORE BLACK AND HISPANIC PATIENTS BY MEASURING TO THE POPULATIONS THEY SERVE RATHER THAN THE CARE THEY PROVIDE. AIM 2 – ADJUST QUALITY MEASURES TO ACCOUNT FOR DIFFERENCES IN PATIENT POPULATIONS IDENTIFIED IN AIM 1 AND COMPARE RANKING FROM ADJUSTED MEASURES TO EXISTING HEDIS/MIPS MEASURES. AIM 3 – EVALUATE HOW ALTERING SPECIFIC ASPECTS OF EXISTING DEPRESSION MEASURES CAN REDUCE BIAS IN COMPARISONS OF CARE EFFECTIVENESS WITHOUT INTRODUCING UNNECESSARY COMPLEXITY. AIM 4 – EXTEND ANALYSES FOR AIMS 1-3 TO PROPOSED OUTCOME-FOCUSED QUALITY MEASURES FOR ANXIETY. AIM 5 – IN COLLABORATION WITH A RANGE OF INTERESTED PARTIES, DEVELOP PROPOSALS FOR IMPROVED OUTCOME-FOCUSED QUALITY MEASURES FOR DEPRESSION AND ANXIETY.

EFFECTIVENESS AND MECHANISMS OF MULTILEVEL IMPLEMENTATION STRATEGIES TO IMPROVE PROVIDER RECOMMENDATION AND ADVANCE HPV VACCINATION: A CLUSTER RANDOMIZED TRIAL - PROJECT ABSTRACT MILLIONS OF US TEENS REMAIN AT RISK OF DEVELOPING HUMAN PAPILLOMAVIRUS (HPV)-RELATED CANCERS DUE TO INADEQUATE HPV VACCINE UPTAKE, DESPITE STRONG ENDORSEMENT IN CLINICAL GUIDELINES AND SUBSTANTIAL PRIOR INTERVENTION EFFORTS. A 2018 NATIONAL SURVEY SHOWED THAT HPV VACCINE COMPLETE SERIES COVERAGE FOR TEENS AGE 13-15 YEARS WAS ONLY 50%, FAR BELOW THE 80% TARGET OF HEALTHY PEOPLE 2020. PRIOR RESEARCH HAS IDENTIFIED STRONG PROVIDER RECOMMENDATION AS THE MOST POWERFUL FACILITATOR OF HPV VACCINE UPTAKE. YET, LITTLE IS KNOWN ABOUT HOW TO LEVERAGE THIS AND OTHER FACILITATORS. ADDITIONALLY, STUDIES HAVE ALSO REVEALED MULTILEVEL, MULTIFACTORIAL BARRIERS TO IMPROVING HPV VACCINATION INCLUDING NEGATIVE PARENTAL PERCEPTIONS AND LIMITATIONS OF HEALTH SYSTEM SUPPORT. FURTHERMORE, EVIDENCE SUGGESTS THAT HPV VACCINE BARRIERS CAN VARY ACROSS DEMOGRAPHIC SUBGROUPS, COMMUNITIES AND CLINICS. DESPITE THIS KNOWLEDGE, MANY PRIOR INTERVENTION STUDIES FOCUS ON SINGLE-LEVEL, SINGLE COMPONENT INTERVENTIONS, LEAVING MANY BARRIERS UNADDRESSED. OF STUDIES THAT ARE MULTILEVEL AND/OR MULTI-COMPONENT, INTERVENTIONS ARE OFTEN PRE-SELECTED TO ADDRESS “TYPICAL” BARRIERS BUT ARE NOT RESPONSIVE TO UNIQUE LOCAL BARRIERS AND LOCAL CONTEXT. TO ADDRESS THIS CRITICAL GAP, WE PROPOSE A 3-ARM CLUSTER RANDOMIZED CONTROLLED TRIAL (RCT) TO COMPARE IMPLEMENTATION STRATEGIES THAT ARE MULTILEVEL AND MULTICOMPONENT AND GUIDED BY IN-DEPTH UNDERSTANDING OF HOW MULTILEVEL FACTORS IN THE PRACTICE SETTINGS MODIFY THE IMPACT OF KEY FACILITATORS SUCH AS PROVIDER RECOMMENDATION. WE WILL USE MIXED METHODS (SURVEYS, INTERVIEWS, ELECTRONIC HEALTH RECORDS) THROUGHOUT; INITIALLY WE WILL EVALUATE BASELINE ASSOCIATIONS BETWEEN PATIENT-, PROVIDER-, AND CLINIC-LEVEL FACTORS AND VARIATIONS IN HPV VACCINATION RATES AND THE QUALITY OF THE PROVIDER RECOMMENDATION (AIM 1). IN AIM 2, WE WILL COMPARE THE EFFECTIVENESS OF: 1) A NOVEL “LOCAL-TAILORED” IMPLEMENTATION STRATEGY, CO- DESIGNED WITH LOCAL CARE TEAMS TO ADDRESS LOCAL BARRIERS AND CONTEXTS; VERSUS 2) A “PRESCRIBED” STRATEGY, TYPICAL OF MOST HEALTH SYSTEMS, THAT INVOLVES PRE-SPECIFIED INTERVENTIONS ADDRESSING PRE-SELECTED VACCINATION BARRIERS; VERSUS 3) USUAL CARE. WE WILL EVALUATE THE EFFECTIVENESS OF THESE STRATEGIES ON IMPROVING HPV VACCINATION (PRIMARY OUTCOME) AND STRENGTHENING PROVIDER RECOMMENDATION (SECONDARY OUTCOME) AS WELL AS ANALYZING COST EFFECTIVENESS. WE WILL ALSO STUDY MECHANISMS OF EFFECT OF THE IMPLEMENTATION STRATEGIES (AIM 3). ALTHOUGH THE NEED OF LOCAL TAILORING SEEMS INTUITIVE, IT IS UNKNOWN IF LOCAL TAILORING WILL YIELD SUPERIOR OUTCOMES THAT COULD OFFSET THE EXTRA INVESTMENT REQUIRED, SUPPORTING THE NEED FOR THIS RCT. WE WILL CONDUCT THE STUDY WITHIN KAISER PERMANENTE SOUTHERN CALIFORNIA, ONE OF THE LARGEST COMMUNITY-BASED PEDIATRIC CARE ORGANIZATIONS IN THE US. OUR STUDY WILL BE GUIDED BY THE CONSOLIDATED FRAMEWORK FOR IMPLEMENTATION RESEARCH AND THE MULTILEVEL FACTORS ACROSS THE CANCER CARE CONTINUUM FRAMEWORK. COMPLETION OF THESE AIMS WILL GENERATE IMPORTANT INSIGHTS INTO THE MULTILEVEL FACTORS ASSOCIATED WITH PROVIDER RECOMMENDATION AND HPV VACCINE UPTAKE. THIS STUDY HAS HIGH POTENTIAL TO GENERATE GUIDANCE FOR DIVERSE HEALTH CARE SETTINGS TO IMPROVE HPV VACCINATION.

COMPUTATIONAL STRATEGIES TO TAILOR EXISTING INTERVENTIONS FOR FIRST MAJOR DEPRESSIVE EPISODES TO INFORM AND TEST PERSONALIZED INTERVENTIONS - ABSTRACT MAJOR DEPRESSIVE DISORDER (MDD) IS A CHRONIC, RECURRENT ILLNESS IMPACTING 20.6% OF THE U.S. POPULATION, CAUSING SIGNIFICANT DISABILITY AND AN ECONOMIC IMPACT OF $326.2 BILLION ANNUALLY. ONE OF THE LARGEST RISK FACTORS FOR DEPRESSION CHRONICITY AND DISABILITY IS INADEQUATE ANTIDEPRESSANT RESPONSE, DEFINED AS LESS THAN A 50% IMPROVEMENT IN DEPRESSIVE SYMPTOMS AFTER STARTING ANTIDEPRESSANT TREATMENT. ANTIDEPRESSANTS ARE RECOMMENDED AS A FIRST-LINE DEPRESSION TREATMENT AND TAKEN BY 70% OF PATIENTS WITH DEPRESSION. INADEQUATE ANTIDEPRESSANT RESPONSE IS EXPERIENCED BY 50-60% OF PATIENTS STARTING AN ANTIDEPRESSANT AND IS RESPONSIBLE FOR 47% OF THE ECONOMIC IMPACT AND DISABILITY CAUSED BY MDD. AS SUCH, IDENTIFYING RISK FOR INADEQUATE ANTIDEPRESSANT RESPONSE EARLY, DURING A PATIENT’S FIRST CLINICAL PRESENTATION FOR A DEPRESSIVE EPISODE, WOULD BE AN INNOVATIVE, URGENTLY NEEDED FIRST STEP TOWARDS PREVENTING RECURRENT DEPRESSIVE EPISODES, REDUCING DEPRESSION CHRONICITY AND DISABILITY, AND IMPROVING MDD OUTCOMES. THIS STEP ALIGNS WITH THE NATIONAL INSTITUTE OF MENTAL HEALTH (NIMH) STRATEGIC PLAN OBJECTIVE 3.2 TO “DEVELOP STRATEGIES FOR TAILORING EXISTING INTERVENTIONS (ANTIDEPRESSANTS) TO OPTIMIZE (DEPRESSIVE EPISODE) OUTCOMES.” WHILE PREVIOUS STUDIES IDENTIFIED SEPARATE PREDICTORS OF ANTIDEPRESSANT RESPONSE, NO STUDY TO DATE HAS FOCUSED ON INTEGRATING KNOWN AND NOVEL PREDICTORS OF INADEQUATE ANTIDEPRESSANT RESPONSE DURING A PATIENT’S FIRST DEPRESSIVE EPISODE. THIS KNOWLEDGE GAP EXISTS AS NO LARGE STUDIES IN DIVERSE POPULATIONS HAVE INTEGRATED COMPREHENSIVE CLINICAL, DEMOGRAPHIC, GENETIC, AND BEHAVIORAL INFORMATION IN ONE MODEL TO PREDICT INADEQUATE ANTIDEPRESSANT RESPONSE PRIOR TO FIRST ANTIDEPRESSANT TREATMENT. SUCH INFORMATION IS CRUCIAL TO IMPROVE PATIENT CARE, REDUCE DEPRESSIVE DISORDER CHRONICITY AND DISABILITY, AND TAILOR EXISTING PATIENT INTERVENTIONS TO OPTIMIZE MDD OUTCOMES. UTILIZING ELECTRONIC HEALTH RECORD DATA FROM THREE LARGE, INTEGRATED HEALTHCARE SYSTEMS REPRESENTING OVER 6.9 MILLION MEMBERS (KAISER PERMANENTE (KP) NORTHERN CALIFORNIA, KP WASHINGTON, AND HEALTHPARTNERS), WE AIM TO QUANTIFY INADEQUATE ANTIDEPRESSANT RESPONSE RISK AT THE TIME OF A PATIENT’S FIRST CLINICAL PRESENTATION FOR A DEPRESSIVE EPISODE BY INTEGRATING CLINICAL, DEMOGRAPHIC, GENETIC, AND BEHAVIORAL INFORMATION IN ONE PREDICTIVE MODEL. TO ACCOMPLISH THIS AIM, WE WILL USE TRANSLATIONAL MACHINE LEARNING AND PREDICTIVE MODELING, INTERNAL AND EXTERNAL MODEL VALIDATION AND TESTING, PROSPECTIVE VALIDATION, AND EXISTING GENOME-WIDE GENOTYPIC DATA. FURTHER, WE WILL EXAMINE BARRIERS AND FACILITATORS TO CLINICAL APPLICATIONS OF PREDICTIVE MODELS FOR MDD TO FACILITATE CLINICAL TRANSLATION AND IMPLEMENTATION OF THE PREDICTIVE MODEL, REDUCING THE TIME BETWEEN RESEARCH INNOVATION AND CLINICAL APPLICATION. OUR LONG-TERM GOAL IS TO DEVELOP A CLINICAL TOOL INFORMING DECISION MAKING AND PROMOTING MDD TREATMENT OPTIMIZATION.

DISSEMINATION OF CVD RISK FACTOR TREATMENT AMONG DIABETIC PATIENTS IN FQHCS

APPROPRIATE GESTATIONAL WEIGHT GAIN IN OVERWEIGHT/OBESE WOMEN

COMPARING TWO GESTATIONAL DIABETES SCREENING METHODS: A PRAGMATIC OUTPATIENT RCT

AMBULATORY BLOOD PRESSURE AND FALLS IN OLDER TREATED PATIENTS WITH HYPERTENSION

PREDICTORS OF WEIGHT LOSS FAILURE AND REGAIN IN BARIATRIC PATIENTS

IMPACT OF IN UTERO MARIJUANA EXPOSURE ON NEURODEVELOPMENT, BEHAVIOR AND MENTAL HEALTH: A LONGITUDINAL BIRTH COHORT STUDY

IDENTIFYING AND SUPPORTING PATIENTS WITH UNDIAGNOSED DEMENTIA USING THE EHR RISK OF ALZHEIMER'S AND DEMENTIA ASSESSMENT RULE (ERADAR): A PILOT CLINICAL TRIAL

BODY COMPOSITION, WEIGHT, AND COLON CANCER SURVIVAL

SEARCH FOR DIABETES IN YOUTH PHASE 3: COHORT STUDY - CALIFORNIA CENTER

METABOLITE PROFILES PRECEDING PROGRESSION TO DIABETES MELLITUS AFTER GESTATIONAL DIABETES

LINKING DNA METHYLATION WITH CHILD MALTREATMENT AND MENTAL HEALTH ACROSS ADOLESCENCE

VIRTUAL POSITIVE PARENTING INTERVENTION TO PROMOTE FILIPINO FAMILY WELLNESS: A RANDOMIZED CONTROLLED TRIAL - FILIPINO YOUTH LIVING IN THE UNITED STATES (US) HAVE SIGNIFICANT BEHAVIORAL HEALTH PROBLEMS, INCLUDING ALARMINGLY HIGH RATES OF ADOLESCENT DEPRESSION, ANXIETY, SUBSTANCE USE, AND SUICIDAL BEHAVIOR. SUBOPTIMAL PARENT-CHILD RELATIONSHIPS AND HARSH DISCIPLINE ARE CRITICAL RISK FACTORS FOR BEHAVIORAL HEALTH PROBLEMS AMONG YOUTH. FILIPINO FAMILIES ALSO FACE ACCULTURATIVE CHALLENGES, PARENTAL SEPARATION DUE TO IMMIGRATION, FAMILY CONFLICT, PARENTAL MENTAL HEALTH DISORDERS, AND MALTREATMENT. FEW, IF ANY PREVENTION PROGRAMS ARE AVAILABLE TO FILIPINOS DESPITE THEIR RAPID POPULATION GROWTH IN THE US. THE INCREDIBLE YEARS® SCHOOL AGE PARENT TRAINING PROGRAM (IY) IS AN EVIDENCE-BASED PREVENTIVE INTERVENTION DESIGNED TO IMPROVE PARENTING SKILLS AND PARENT-CHILD RELATIONSHIPS AMONG FAMILIES WITH SCHOOL AGE YOUTH. AS A RESULT OF PILOT STUDIES FUNDED THROUGH A K23 GRANT FROM NICHD, A KL2 GRANT FROM NCATS, WE HAVE DEMONSTRATED IY EFFICACY IN IMPROVING POSITIVE PARENTING PRACTICES AND CHILD DEPRESSION AND ANXIETY SYMPTOMS IN FILIPINO FAMILIES. WE HAVE IMPROVED THE INTERVENTION PROTOCOL FOR USE ONLINE WITH OLDER CHILDREN AND SECURED AGREEMENTS FROM COMMUNITY AGENCIES TO PARTICIPATE IN THE PROJECT. FURTHER RESEARCH IS NEEDED ON THE EFFECTIVENESS OF ONLINE IY, AND THE IMPACT OF ENGAGEMENT (I.E., ATTENDANCE) ON INTERVENTION OUTCOMES AS WELL AS THE BARRIERS AND FACILITATORS TO IMPLEMENTATION BY PROVIDERS IN COMMUNITY AGENCIES. BUILDING UPON ONGOING COLLABORATIVE RESEARCH AND COMMUNITY AWARENESS-RAISING WITHIN FILIPINO COMMUNITIES IN CALIFORNIA, WE PROPOSE A TYPE 1 HYBRID, INDIVIDUALLY GROUP RANDOMIZED TREATMENT TRIAL TO COMPARE IY WITH A USUAL CARE CONTROL GROUP WHO WILL RECEIVE IY AFTER 3 MONTHS. SPECIFICALLY, THE STUDY SEEKS TO RECRUIT A SAMPLE OF 250 FILIPINO PARENTS AND CHILDREN AGES 8-12 YEARS THROUGH COMMUNITY ORGANIZATIONS IN CALIFORNIA. PARTICIPANTS IN BOTH GROUPS WILL BE FOLLOWED FOR A MINIMUM OF 6 MONTHS WITH ASSESSMENTS THAT INCLUDE PARENT-REPORT AND CHILD-REPORT. OUR PRIMARY OBJECTIVE IS TO TEST THE EFFECTIVENESS OF ONLINE IY ON OUR PRIMARY OUTCOMES: PARENT-REPORTED PARENTING PRACTICES (POSITIVE VERBAL DISCIPLINE), CHILD-REPORTED CHILD DEPRESSION AND ANXIETY SYMPTOMS, AND SECONDARY OUTCOMES: PARENT-REPORTED PHYSICAL PUNISHMENT, PARENT- REPORTED CHILD INTERNALIZING BEHAVIOR, PARENT-REPORTED CHILD DEPRESSION & ANXIETY SYMPTOMS, AND PARENT- AND CHILD-REPORTED YOUTH RESILIENCE. OUR SPECIFIC AIMS ARE: 1) TO TEST THE EFFECTIVENESS OF THE ONLINE INCREDIBLE YEARS® MODEL OF PARENT TRAINING AND ITS IMPACT ON PRIMARY AND SECONDARY OUTCOMES; 2) TO DETERMINE THE IMPACT OF ENGAGEMENT (I.E., IY ATTENDANCE) ON PRIMARY OUTCOMES; AND 3) TO DESCRIBE INTERVENTION DELIVERY AND ITS ONLINE IMPLEMENTATION IN REAL-WORLD COMMUNITY SETTINGS. WE WILL UTILIZE QUANTITATIVE AND QUALITATIVE RESEARCH METHODOLOGIES TO ADVANCE THE SCIENTIFIC UNDERSTANDING OF PARENTING INTERVENTIONS DURING MIDDLE CHILDHOOD. IF THE APPROACH AND INTERVENTION FORMAT SUCCEED WITH FILIPINOS, COMPARABLE STRATEGIES COULD BE USED EFFECTIVELY REACH OTHER IMMIGRANT OR MINORITY POPULATIONS, MANY OF WHOM ARE RELUCTANT TO SEEK PREVENTIVE PARENTING PROGRAMS.

ASSISTED IDENTIFICATION AND NAVIGATION OF EARLY MENTAL HEALTH SYMPTOMS IN CHILDREN - ABSTRACT ABOUT 55% OF CHILDREN WITH SIGNIFICANT MENTAL HEALTH DIFFICULTIES RECEIVE TREATMENT AND UP TO 80% OF CHILDREN WITH SUB-CLINICAL SYMPTOMS RECEIVE NO TREATMENT. TREATMENTS ARE OFTEN NOT INITIATED UNTIL ISSUES ARE SIGNIFICANTLY IMPACTING THE CHILD AND FAMILY. THIS STUDY AIMS TO CONDUCT A PRAGMATIC RANDOMIZED TRIAL IN TWO NON-ACADEMIC HEALTH CARE SYSTEMS TO TEST A MENTAL HEALTH FAMILY NAVIGATOR MODEL TO PROMOTE EARLY ACCESS TO, ENGAGEMENT IN, AND COORDINATION OF NEEDED MENTAL HEALTH SERVICES FOR CHILDREN. THE FIRST TASK OF THE STUDY WILL FOCUS ON THE IMPLEMENTATION OF A PREDICTIVE MODEL TO IDENTIFY SYMPTOMATIC CHILDREN WITH NO DIAGNOSED MENTAL HEALTH DISORDER(S) OR TREATMENTS INITIATED. THE TOOL IDENTIFIES PATIENTS WITH DOCUMENTATION OF MENTAL HEALTH SYMPTOMS OR COMPLAINTS IN THE FREE TEXT OF A PROGRESS NOTE FROM A RECENT PRIMARY CARE OR URGENT CARE VISIT. USING THIS PREDICTIVE ALGORITHM, WE WILL CONDUCT A PRAGMATIC RANDOMIZED TRIAL COMPARING INTERVENTION AND USUAL CARE ARM PATIENTS ENROLLED FROM KAISER PERMANENTE (KP) WASHINGTON AND KP NORTHERN CALIFORNIA. THE TRIAL WILL ENROLL 200 PATIENTS PER ARM (N=400). CHILDREN WITH (1) A NEW MENTAL HEALTH DIAGNOSIS BUT NO TREATMENT INITIATED; (2) A NEW MENTAL HEALTH MEDICATION ORDERED WITH NO MENTAL HEALTH DIAGNOSIS; AND (3) SYMPTOMS IDENTIFIED BY THE PREDICTIVE MODEL WITH NO NEW MENTAL HEALTH DIAGNOSIS OR TREATMENT INITIATED WILL BE RECRUITED. THE STUDY INTERVENTION WILL OFFER 6 MONTHS OF SUPPORT TO THE FAMILY BY A MENTAL HEALTH NAVIGATOR (SOCIAL WORKER). THE NAVIGATOR WILL PERFORM AN INITIAL NEEDS AND BARRIERS ASSESSMENT WITH THE FAMILY AROUND MENTAL HEALTH SERVICES, CONDUCT ONGOING MOTIVATIONAL INTERVIEWING AROUND MENTAL HEALTH CARE, PROVIDE UP TO 4 PSYCHOTHERAPY SESSIONS (WHEN APPROPRIATE) VIA CLINIC-TO-HOME VIDEO VISITS, HELP THE FAMILY FIND AND SCHEDULE WITH APPROPRIATE MENTAL HEALTH PROVIDERS IN THE COMMUNITY, AND REACH OUT AD HOC IF MENTAL HEALTH APPOINTMENTS OR MEDICATION REFILLS ARE MISSED. THE PRIMARY OUTCOME IS THE PERCENTAGE OF YOUTH INITIATING PSYCHOTHERAPY. THE SECONDARY OUTCOME IS THE PERCENTAGE OF YOUTH WITH AT LEAST 4 MENTAL HEALTH VISITS. WE HYPOTHESIZE THAT THE INTERVENTION ARM WILL HAVE HIGHER RATES OF PSYCHOTHERAPY USE COMPARED TO THE CONTROL ARM. WE WILL ALSO ASSESS INITIATION OF PSYCHOTROPIC MEDICATIONS. ALL PRIMARY ANALYSES WILL FOLLOW AN INTENT-TO-TREAT APPROACH. A WAIVER OF CONSENT WILL BE OBTAINED TO INCLUDE DATA FOR ALL INDIVIDUALS OFFERED THE INTERVENTION IN THE ANALYSIS, REGARDLESS OF THE AMOUNT OF INTERVENTION (“DOSE” OF NAVIGATION) RECEIVED.

URINARY DIVERSION AMONG BLADDER CANCER SURVIVORS: COST, COMPLICATIONS, AND QOL

DE PI? Y A MOVERNOS STUDY: PROMOTING PHYSICAL ACTIVITY IN OLDER LATINX ADULTS - SUMMARY LATINX OLDER ADULTS ARE AT HIGHER RISK FOR DEVELOPING ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD) THAN WHITE OLDER ADULTS. DESPITE OLDER LATINX ADULTS HAVING LOWER RATES OF PHYSICAL ACTIVITY (PA) AND A HIGH BURDEN OF COMORBIDITIES THAT ARE ASSOCIATED WITH ADRD, FEW STUDIES HAVE TARGETED THIS POPULATION WITH THEORY-BASED AND CULTURALLY ADAPTED APPROACHES TO REDUCE RISK FOR ADRD. BUILDING ON PILOT WORK BY THE TEAM, THE PROPOSED PROJECT WOULD ALLOW US TO CULTURALLY ADAPT A THEORY-BASED INTERVENTION TO PROMOTE MODERATE-TO-VIGOROUS PHYSICAL ACTIVITY (MVPA) FOR LATINX ADULTS AGES 55 TO 89 YEARS. IN STAGE I (R61/AIM 1), WE WILL FINALIZE THE RECRUITMENT AND INTERVENTION STRATEGY (INCLUDING FINALIZING THE TARGET MECHANISMS OF ADHERENCE TO MVPA, INITIAL CULTURAL ADAPTATION AND TRANSLATION) THROUGH MEETINGS WITH OUR COMMUNITY ADVISORY BOARD AND PILOT TESTING WITH 10 LATINX ADULTS. IN STAGE II (R33/AIM 2), WE WILL RANDOMIZE 130 LATINX ADULTS TO RECEIVE THE 16-WEEK, FULLY REMOTE DE PIE Y A MOVERNOS (DE PIE) INTERVENTION OR A CONTROL CONDITION. THE INTERVENTION WILL TARGET THE MECHANISMS OF SELF-EFFICACY, PA HABIT STRENGTH, SOCIAL SUPPORT, AND PA ENJOYMENT USING A STAIRCASE APPROACH WHERE PARTICIPANTS WILL INITIALLY REDUCE THEIR SITTING BY MOVING MORE TO BUILD CONFIDENCE TOWARDS ENGAGING IN MVPA. PARTICIPANTS WILL ALSO RECEIVE A FITBIT ACTIVITY TRACKER, HEALTH COACHING CONTACTS, FEEDBACK ON MEETING GOALS, AND WILL IDENTIFY A SUPPORT PERSON. WE WILL DETERMINE THE EFFECT OF THE DE PIE INTERVENTION ON ACTIVPAL ACCELEROMETER-BASED MVPA MINUTES/DAY (PRIMARY OUTCOME) AND ADHERENCE TO MEETING THE MVPA GUIDELINES OF 150 MINUTES PER WEEK (SECONDARY OUTCOME). FURTHER, MEDIATION ANALYSES WILL BE CONDUCTED TO DETERMINE THE EFFECT OF THE INTERVENTION ON MECHANISMS OF ADHERENCE (SELF-EFFICACY, HABIT STRENGTH, SOCIAL SUPPORT, ENJOYMENT) AND IDENTIFY WHETHER THESE MECHANISMS EXPLAIN INTERVENTION EFFECTS ON MVPA MINUTES/WEEK AND ADHERENCE TO MVPA GUIDELINES. WE WILL EXPLORE COGNITION, ACCULTURATION, AGE AND SEX AS MODERATORS OF THESE ASSOCIATIONS. RESULTS WILL HELP IDENTIFY IMPORTANT MECHANISMS OF ADHERENCE TO MVPA AND INFORM CULTURALLY ADAPTED, THEORY- BASED APPROACHES TO PREVENT ADRD IN THE LATINX COMMUNITY.

SELF-TESTING OPTIONS IN THE ERA OF PRIMARY HPV SCREENING FOR CERVICAL CANCER: THE STEP TRIAL

POPULATION-BASED PHARMACOGENOMIC ASSESSMENT OF QT PROLONGATION

VITAMIN D, RACE/ETHNICITY, GENOTYPE, AND MULTIPLE SCLEROSIS

SARS-COV-2 SEROLOGICAL ANTIBODY TESTING FOR DISEASE SURVEILLANCE AND CLINICAL USE

ASSESSING SYNDEMICS OF CARDIOVASCULAR DISEASE IN PEOPLE WITH AND WITHOUT HIV - PROJECT SUMMARY/ABSTRACT COMBINATION ANTIRETROVIRAL THERAPY (ART) HAS LED TO DRAMATIC DECLINES IN MORBIDITY AND MORTALITY FOR PEOPLE WITH HIV (PWH). HOWEVER, AS PWH AGE, THE RISK OF CARDIOVASCULAR DISEASE (CVD) HAS INCREASED, WITH A PROJECTED LIFETIME BURDEN AMONG PWH OF 65% FOR MEN AND 44% FOR WOMEN. THE HIGHER OBSERVED RISK OF CVD IN PWH COMPARED WITH THE GENERAL POPULATION IS A RESULT OF THE HIGHER PREVALENCE OF ESTABLISHED CVD RISK FACTORS (SMOKING, ALCOHOL, DYSLIPIDEMIA), AND DIRECT EFFECTS OF HIV INFECTION, INCLUDING IMMUNODEFICIENCY AND INFLAMMATION. RECENT STUDIES HAVE ALSO IMPLICATED INTEGRASE STRAND INHIBITORS AND OTHER ART WITH INCREASES IN BODY WEIGHT, WHICH MAY FURTHER INCREASE RISK OF CVD. THERE ARE ALSO MANY UNDERSTUDIED SOCIAL AND ECONOMIC CONDITIONS THAT MAY CONTRIBUTE TO THE HIGH CVD RISK IN PWH, INCLUDING DISPARITIES IN HEALTHCARE ACCESS AND TREATMENT, SOCIAL ISOLATION, HISTORY OF TRAUMA, AND HIV STIGMA. WHILE MOST STUDIES HAVE CONSIDERED THE IMPACT OF CVD RISK FACTORS IN ISOLATION, IT IS WELL KNOWN THAT MANY FREQUENTLY CO-OCCUR, SUCH AS SMOKING, ALCOHOL, OBESITY AND DEPRESSION. FURTHERMORE, THE WAYS IN WHICH SOCIAL FACTORS EXACERBATE THE EFFECT OF BIOMEDICAL CVD RISK FACTORS AMONG PWH IS NOT WELL UNDERSTOOD. USING A SYNDEMICS FRAMEWORK, WHICH IS UNIQUELY SUITED FOR THE EVALUATION OF THE CLUSTERING OF SOCIAL AND BIOLOGICAL CONDITIONS IN VULNERABLE POPULATIONS, WE WILL INVESTIGATE REASONS FOR THE PERSISTENTLY HIGH RISK OF CVD AMONG PWH. WITH THE TEAM’S INTERDISCIPLINARY EXPERTISE IN HIV, CVD AND SYNDEMICS, OUR STUDY IS DESIGNED TO UNDERSTAND HOW SOCIAL, ECONOMIC AND BIOLOGICAL FACTORS COMBINE IN PWH, CONTRIBUTING TO THEIR HIGH CVD RISK. WE WILL LEVERAGE COMPREHENSIVE ELECTRONIC HEALTH RECORD (EHR) DATA FROM KAISER PERMANENTE (KP) AND DETAILED EXISTING SURVEY AND BIOSPECIMEN FROM THE KP RESEARCH BANK (KPRB). IN AIM 1, WE WILL EXAMINE SYNERGISTIC RELATIONSHIPS WITH MAJOR ADVERSE CARDIOVASCULAR EVENTS (MACE) AMONG 29,000 PWH AND 1:20 MATCHED PEOPLE WITHOUT HIV (PWOH) ENROLLED IN KP FROM 2000-2021. WE WILL EVALUATE CLUSTERS OF SOCIAL AND BIOLOGICAL FACTORS AVAILABLE IN EHRS SUCH AS MENTAL HEALTH, SUBSTANCE USE DISORDERS (SUD), NEIGHBORHOOD DEPRIVATION, AND INSURANCE BENEFITS. FOR AIM 2, WE WILL PERFORM A COMPLEMENTARY STUDY WITHIN THE KPRB TO IDENTIFY SYNERGISTIC RELATIONSHIPS WITH SUBCLINICAL CVD AMONG 1,969 PWH (709 WITH BIOSPECIMENS) AND 1:1 MATCHED PWOH. WE WILL CONSIDER ADDITIONAL SOCIAL FACTORS FROM SURVEYS THAT MAY IMPACT CVD RISK, INCLUDING DISCRIMINATION AND STIGMA, SOCIAL ISOLATION, EMOTIONAL AND PRACTICAL HEALTH SUPPORT, AND ECONOMIC FACTORS. FINALLY, AIM 3 WILL INVOLVE RECRUITMENT OF 60 PWH FROM HIGH-RISK CLUSTERS IDENTIFIED IN AIMS 1 AND 2 FOR IN-DEPTH QUALITATIVE INTERVIEWS TO EXPLORE HOW THE SYNDEMIC CONDITIONS CONTRIBUTE TO THE HIGH CVD RISK. THE INTERVIEWS WILL INFORM A FOLLOW-UP SURVEY OF 350 PWH RECRUITED FROM THE SAME HIGH- RISK CLUSTERS, TO CONFIRM SYNDEMIC CONDITIONS IN A LARGER SAMPLE THAT COULD BE ADDRESSED IN FUTURE CVD PREVENTION EFFORTS. INTEGRATING QUANTITATIVE AND QUALITATIVE DATA SOURCES, THIS STUDY HAS GREAT POTENTIAL TO INFORM FUTURE COMPREHENSIVE COMMUNITY- AND HEALTH SYSTEM-LEVEL INTERVENTIONS TO REDUCE THE CVD BURDEN IN PWH.

CARDIOVASCULAR DISEASE AMONG ASIANS AND PACIFIC ISLANDERS (CASPER)

PRENATAL BISPHENOL A EXPOSURE AND RISK OF GESTATIONAL DIABETES

CLUSTER RANDOMIZED TRIAL OF A MOBILE HEALTH INTERVENTION TO ACHIEVE APPROPRIATE GESTATIONAL WEIGHT GAIN IN OVERWEIGHT/OBESE WOMEN

STATIN TREATMENT AND INCIDENT ALZHEIMER'S DISEASE AND RELATED DEMENTIAS IN A LARGE, MULTI-ETHNIC HEALTH PLAN

PRE-VISIT PRIORITIZATION FOR COMPLEX PRIMARY CARE PATIENTS WITH DIABETES

COHERE ? CONTEXTUALIZED CARE IN CHCS? ELECTRONIC HEALTH RECORDS

INFORMATICS APPROACHES TO ASSESSING PATIENT FRAILTY IN SURGICAL CARE

PREDICTING EXACERBATIONS OF ASTHMA IN REAL-WORLD PATIENTS WITH LOW MEDICAL UTILIZATION (PEARL) - PROJECT SUMMARY ASTHMA IS A CHRONIC INFLAMMATORY CONDITION THAT AFFECTS > 20 MILLION AMERICANS. THE PREVALENCE OF ASTHMA HAS BEEN INCREASING SINCE THE EARLY 1980S IN ALL AGE, SEX, AND RACIAL GROUPS. THERE IS NO UNIVERSAL METHOD FOR DE- TERMINING ASTHMA SEVERITY. THE TERMINOLOGY AND THE DEFINITION USED IN VARIOUS ASTHMA GUIDELINES HAVE EVOLVED OVER TIME. MOST COMMONLY, ASTHMA SEVERITY IS DETERMINED BY CLINICAL PARAMETERS SUCH AS MEDICA- TION USE, PRESENCE AND/OR FREQUENCY OF ASTHMA SYMPTOMS, NUMBER OF ASTHMA EXACERBATIONS (WHICH ARE ACUTE OR SUBACUTE EPISODES OF PROGRESSIVELY WORSENING SHORTNESS OF BREATH, COUGH, WHEEZING, AND CHEST TIGHT- NESS OR SOME COMBINATION OF THESE SYMPTOMS), AND/OR THE RESULTS OF LUNG FUNCTION TESTS. PATIENTS WITH PERSIS- TENT ASTHMA ARE AT ELEVATED RISK FOR EXACERBATIONS (ATTACK) AND OFTEN HAVE DECREASED LUNG FUNCTION. YET THE BUR- DEN OF INTERMITTENT ASTHMA IS ALSO SIGNIFICANT: IT AFFECTS 50-75% OF ALL ASTHMA PATIENTS AND REPRESENTS 30-40% OF TOTAL ASTHMA EXACERBATIONS REQUIRING EMERGENCY CONSULTATION. RISK FACTORS FOR ASTHMA EXACERBATIONS HAVE BEEN STUDIED IN PATIENTS WITH PERSISTENT ASTHMA. HOWEVER, LITTLE IS KNOWN ABOUT RISK FACTORS IN PATIENTS WITH IN- TERMITTENT ASTHMA, NOR HAVE RISK PREDICTION MODELS BEEN REPORTED. A FOCUSED STUDY ON RISK FACTOR IDENTIFICATION AND FUTURE RISK PREDICTION WILL PROVIDE VALUABLE INSIGHTS INTO THE ETIOLOGY OF ASTHMA EXACERBATIONS IN INTERMITTENT ASTHMA PATIENTS AND FACILITATE A PERSONALIZED APPROACH IN THE MANAGEMENT OF THE DISEASE. WITHOUT A CLEAR UN- DERSTANDING OF THE RISK OF ASTHMA EXACERBATION FOR EACH INDIVIDUAL PATIENT WITH INTERMITTENT ASTHMA, WE WILL NOT BE ABLE TO OPTIMALLY DEFINE THE MOST APPROPRIATE INTERVENTION STRATEGIES TO REDUCE THE BURDEN OF THE DISEASE IN THIS GROUP OF PATIENTS. TO OPERATIONALIZE THE CLINICAL DEFINITION OF INTERMITTENT ASTHMA, WE WILL FOCUS ON A PHENO- TYPIC GROUP OF LOW UTILIZERS REFERRED TO IN GUIDELINES AS INTERMITTENT ASTHMA. WE PROPOSE TO IDENTIFY POTENTIAL RISK FACTORS FOR ASTHMA EXACERBATION IN LOW UTILIZERS USING HIGH-DIMENSIONAL AND LONGITUDINAL KPSC EHR AND EXTER- NAL DATA SOURCES (INCLUDING AIR QUALITY MEASURES, SOCIAL DETERMINANTS OF HEALTH AND VIOLENT CRIME), SUBSEQUENTLY DEVELOP AND VALIDATE RISK PREDICTION MODELS TO STRATIFY PATIENTS INTO LOW- AND HIGH-RISK GROUPS, AND EXTERNALLY VALIDATE THE RISK PREDICTION MODEL USING EHR DATA OF ANOTHER LARGE HEALTH CARE ORGANIZATION. WE ALSO PROPOSE TO ESTABLISH A PROSPECTIVE COHORT OF LOW UTILIZERS AND COLLECT PATIENT-REPORTED INFORMATION (PRI) VIA A SURVEY. THE PRI WILL HELP CHARACTERIZE THE PATIENTS OF LOW UTILIZERS IN TERMS OF ASTHMA SYMPTOMS, ACTIVITIES, IMPAIRMENT AND RISK ASSESSMENT, WORK PRODUCTIVITY, BELIEFS ABOUT MEDICINES AND ANXIETY/DEPRESSION SCALES. WE WILL DEVELOP AND INTERNALLY VALIDATE A RISK PREDICTION MODEL BASED ON BOTH EHR AND PRI DATA. THE PROPOSED MODELS WILL AL- LOW PHYSICIANS TO PROVIDE PERSONALIZED CARE (E.G., DEVELOP OR ADJUST TREATMENT PLANS, PROVIDE PERSONAL ASTHMA ACTION PLANS ACCORDINGLY, AND REFER PATIENTS TO ASTHMA SPECIALISTS WHEN NECESSARY) AND THUS IMPROVE THE QUAL- ITY OF CARE AND REDUCE ASTHMA BURDEN. OUR PROPOSAL TO EXAMINE HETEROGENEITY ACROSS DIFFERENT RACIAL/ETHNIC GROUPS HAS THE POTENTIAL TO INFORM PRACTICE FOR MORE ACCURATE ASTHMA RISK ASSESSMENT.

DETERMINANTS OF MIDLIFE & LONGITUDINAL CHANGE IN COGNITIVE FUNCTION: CARDIA STUDY

IDENTIFICATION OF DNA METHYLATION MARKERS FOR RISK OF METASTASIS IN LOCALIZED PRO

2/3 COMPAAAS TRIPARTITE: ART-CC, KP, AND VA

CATALYST: CONSORTIUM FOR APPLIED TRAINING TO ADVANCE THE LEARNING HEALTH SYSTEM WITH SCHOLARS/TRAINEES

ZOSTER VACCINE AND RISK FACTORS OF ZOSTER AND POST-HERPETIC NEURALGIA

A RANDOMIZED, CONTROLLED TRIAL OF A TELEPHONE-BASED DEVELOPMENTAL CARE COORDINATION SYSTEM

IMPACT OF SUGARY BEVERAGE TAXES ON WEIGHT AND HEALTH OUTCOMES AFTER 3-5 YEARS

DIABETES AND AGING IN A MULTI-ETHNIC POPULATION

UNDERSTANDING DISPARITIES IN PREVENTIVE SERVICES FOR PATIENTS WITH MENTAL ILLNESS

THE BARIATRIC EXPERIENCE LONG TERM (BELONG) II FOR RACIAL AND ETHNIC MINORITY PATIENTS

HIV STATUS AND INCIDENCE AND OUTCOMES OF HEART FAILURE

INTEGRATING GENETIC TESTING FOR LYNCH SYNDROME IN A MANAGED CARE SETTING

SLEEP FOR HEALTH: A RANDOMIZED CLINICAL TRIAL EXAMINING THE EFFECTS OF COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA ON DIABETES RISK - PROJECT SUMMARY/ABSTRACT TYPE 2 DIABETES MELLITUS (T2D) IS A MAJOR CAUSE OF BLINDNESS, KIDNEY FAILURE, CARDIOVASCULAR DISEASE, AMPUTATIONS, REDUCED QUALITY OF LIFE, AND PREMATURE DEATH IN THE UNITED STATES, AND IT IS EXPECTED THAT ONE IN THREE AMERICANS WILL HAVE T2D BY 2050. TO STEM THE TIDE OF THIS HEALTH CRISIS, NEW STRATEGIES ARE NEEDED TO PREVENT THE PROGRESSION TO T2D FROM PREDIABETES—ELEVATED GLUCOSE LEVELS THAT ARE NOT YET IN THE DIABETES RANGE. A GROWING BODY OF RESEARCH SUGGESTS THAT INSOMNIA IS A MAJOR MODIFIABLE RISK FACTOR FOR PROGRESSION TO DIABETES. THE PROPOSED STUDY WOULD BUILD OFF A PROMISING FEASIBILITY STUDY TO TEST WHETHER PROVIDING COGNITIVE BEHAVIORAL THERAPY FOR INSOMNIA (CBT-I) TO PATIENTS WITH PREDIABETES RESULTS IN A REDUCTION IN GLUCOSE LEVELS COMPARED TO A PATIENT EDUCATION CONTROL PROGRAM. IF SO, THIS INSOMNIA TREATMENT COULD BE AN EFFECTIVE TOOL TO PREVENT DIABETES. INDIVIDUALS WITH PREDIABETES AND INSOMNIA WILL BE RANDOMIZED TO RECEIVE SIX SESSIONS OF A DEPLOYMENT-READY DIGITAL CBT-I PROGRAM, PROVIDING STANDARD-OF-CARE TREATMENT FOR INSOMNIA (INTERVENTION ARM, N = 150), OR A PATIENT EDUCATION WEBSITE PROVIDING NONTAILORED EDUCATIONAL MATERIAL ABOUT INSOMNIA (CONTROL ARM, N = 150). WE WILL COMPLETE ASSESSMENTS AT BASELINE, AT 10 WEEKS (AFTER THE CONCLUSION OF THE INTERVENTION AND CONTROL PROGRAMS), AND AT 32 WEEKS POST-BASELINE, MEASURING HYPERGLYCEMIA, OBJECTIVE AND SUBJECTIVE MEASURES OF SLEEP, AND POTENTIAL MEDIATING VARIABLES INCLUDING DIET, EXERCISE, AND MOOD. WE WILL ALSO COLLECT AND STORE BLOOD SAMPLES TO ALLOW FOR ASSESSMENT OF METABOLIC MECHANISMS IN FUTURE RESEARCH. WE WILL ASSESS (1) WHETHER INDIVIDUALS RANDOMIZED TO THE INTERVENTION ARM HAVE LOWER RATES OF HYPERGLYCEMIA, AS MEASURED BY ORAL GLUCOSE TOLERANCE TESTING AND VARIOUS SECONDARY MEASURES, THAN INDIVIDUALS RANDOMIZED TO THE CONTROL ARM AT 10 WEEKS AND 32 WEEKS AFTER BASELINE; (2) WHETHER IMPROVEMENTS IN SLEEP AFTER BASELINE ARE ASSOCIATED WITH DECREASES IN HYPERGLYCEMIA, REGARDLESS OF STUDY ARM; AND (3) WHETHER ANY EFFECTS OF THE INTERVENTION ON HYPERGLYCEMIA ARE MEDIATED BY IMPROVEMENTS IN SLEEP, DIET, EXERCISE, AND/OR MOOD. THIS RESEARCH WILL SERVE AS A CRITICAL STEP IN IDENTIFYING A POTENTIALLY DRAMATIC TOOL FOR IMPROVING HEALTH OUTCOMES FOR AMERICANS AT RISK OF T2D. SLEEP INTERVENTIONS CAN LEAD TO SUSTAINED IMPROVEMENTS THAT ARE INTRINSICALLY REWARDING TO PATIENTS. IF EFFECTIVE, DIGITAL CBT-I COULD PROVIDE A POWERFUL PATHWAY TO PREVENTING DIABETES FOR MILLIONS OF PATIENTS WITH PREDIABETES.

SKELETAL HEALTH OUTCOMES AMONG US ASIAN WOMEN - PROJECT SUMMARY/ABSTRACT BOTH ETHNIC DIVERSITY AND THE BURDEN OF OSTEOPOROSIS HAVE INCREASED WITH THE AGING US POPULATION. ASIANS NOW COMPRISE 7% OF THE US AND 17% OF CALIFORNIA’S POPULATION, THE STATE IN WHICH NEARLY ONE THIRD OF ALL US ASIANS RESIDE. IN 2002, THE US PREVENTIVE SERVICES TASK FORCE UPDATED RECOMMENDATIONS FOR OSTEOPOROSIS SCREENING TO ALL WOMEN AGE 65 YEARS AND OLDER. BECAUSE ASIANS HAVE LOWER BONE DENSITY THAN WHITES, THEY HAVE A GREATER LIKELIHOOD OF BEING DIAGNOSED WITH OSTEOPOROSIS ON THE BASIS OF THEIR BONE DENSITY SCREENING TEST RESULTS, YET THEY HAVE A LOWER RISK OF HIP FRACTURE. EXISTING FRACTURE RISK CALCULATORS CONSIDER RACE/ETHNICITY IN ESTIMATING FRACTURE RISK, BUT THE INHERENT ASSUMPTIONS REMAIN LARGELY UNTESTED. THE MOST WIDELY USED CALCULATOR IS FRAX, WHICH PROVIDES 10-YEAR RISK ESTIMATES OF HIP AND ANY ONE OF FOUR MAJOR OSTEOPOROTIC FRACTURES FOR WHITE, BLACK, HISPANIC, AND ASIAN RACE. FOR US ASIANS, AN ADJUSTMENT FACTOR (0.5 FOR WOMEN) IS APPLIED DURING FRACTURE RISK CALCULATION, BASED ON EPIDEMIOLOGIC STUDIES INDICATING THAT US ASIAN WOMEN HAVE A 40-50% LOWER INCIDENCE OF HIP FRACTURE THAN WHITE WOMEN. HOWEVER, DATA FOR FRACTURES OTHER THAN HIP ARE LIMITED FOR ASIANS, AND POPULATION FRACTURE DATA BY ASIAN ETHNIC SUBGROUPS ARE LARGELY LACKING. US ASIANS COMPRISE A HETEROGENEOUS POPULATION WHOSE ANCESTRY ORIGINATES PRIMARILY FROM EAST, SOUTH, AND SOUTHEAST ASIA; IN CALIFORNIA, THE TWO LARGEST SUBGROUPS ARE FILIPINO AND CHINESE. IT IS NOTABLE THAT USING THE SAME AGE, GENDER, BONE DENSITY, AND CLINICAL PROFILE, FRAX CALCULATORS PRODUCE DIFFERENT RESULTS FOR US ASIAN VERSUS ASIANS IN HONG KONG AND TAIWAN (BOTH HIGHER), CHINA (SIMILAR), AND THE PHILIPPINES (LOWER). THESE DIFFERENCES COULD STEM FROM DIFFERENCES IN FRACTURE EPIDEMIOLOGY IN THESE COUNTRIES. A MORE PRECISE UNDERSTANDING OF FRACTURE RISK IN US ASIANS IS PARAMOUNT FOR TAILORING THEIR FRACTURE PREVENTION COUNSELING AND CARE. USING DATA FROM KAISER PERMANENTE NORTHERN CALIFORNIA, A LARGE INTEGRATED HEALTHCARE DELIVERY SYSTEM WITH MEMBERSHIP ACROSS NORTHERN CALIFORNIA AND ESPECIALLY IN THE SAN FRANCISCO BAY AREA AND SACRAMENTO REGIONS (WHERE LARGE NUMBERS OF ASIANS RESIDE), THIS PROPOSED STUDY WILL CONDUCT THE FIRST LARGE-SCALE ASSESSMENT OF BONE DENSITY AND FRACTURE OUTCOMES AMONG US ASIANS AND ASIAN ETHNIC MINORITIES. OUR THREE PRIMARY AIMS ARE: (1) TO COMPARE THE INCIDENCE OF HIP AND MAJOR OSTEOPOROTIC FRACTURES FOR WHITE AND ASIAN MEN AND WOMEN AND BY ASIAN ETHNIC MINORITIES; (2) TO CHARACTERIZE THE ASSOCIATION BETWEEN BONE DENSITY AND FRACTURE RISK FOR ASIAN WOMEN IN RELATION TO FINDINGS OBSERVED FOR WHITE WOMEN; AND (3) TO EXAMINE THE PREDICTIVE ACCURACY OF FRACTURE RISK TOOLS FOR ASIAN WOMEN AND TO DETERMINE WHETHER REPLACEMENT OF EXISTING BASE POPULATION FRACTURE DATA WITH ASIAN-SPECIFIC FRACTURE DATA YIELDS MORE ACCURATE FRACTURE RISK PREDICTION FOR ASIANS. FINDINGS FROM THIS STUDY WILL PROVIDE A MORE ACCURATE WAY TO CALCULATE FRACTURE RISK IN US ASIANS AND, IN THE FUTURE, COULD ENABLE MILLIONS OF ASIAN AMERICANS TO OBTAIN FRACTURE RISK DATA TAILORED TO THEIR ETHNIC PROFILE.

NEW RISK MODELS FOR DIABETES COMPLICATIONS USING ELECTRONIC HEALTH RECORDS - ABSTRACT DIABETES INCIDENCE AND PREVALENCE REMAIN AT RECORD HIGHS IN THE UNITED STATES. UNDERSTANDING DIABETES DISEASE PROGRESSION AND HOW IT VARIES AMONG AMERICA’S HETEROGENEOUS POPULATION IS CRITICAL, GIVEN UNEQUAL RISKS AND OUTCOMES FOR INDIVIDUALS OF DIFFERENT RACIAL/ETHNIC GROUPS. DIABETES OUTCOME PREDICTION AND SIMULATION MODELS ALLOW PREDICTION OF A PERSON’S RISK FOR DIABETES COMPLICATIONS AND DEATH. A RECENT REVIEW OF 19 SUCH MODELS FOUND THAT THE MAJORITY—16 MODELS—RELIED AT LEAST PARTLY ON TRANSITION FUNCTIONS DEVELOPED BY THE UNITED KINGDOM PROSPECTIVE DIABETES STUDY (UKPDS). THE UKPDS DRAWS ON DATA FROM A TRIAL THAT BEGAN IN 1977 AND INVOLVED 5100 PATIENTS WHO WERE FOLLOWED FOR A TOTAL OF 89,760 PERSON YEARS. THE SAMPLE CONSISTED OF MOSTLY WHITE BRITISH CITIZENS. ONLY 8% AND 10% OF THE UKPDS SAMPLE WERE INDIAN ASIAN AND AFRO- CARIBBEAN PATIENTS, RESPECTIVELY. THE MAJOR RACIAL/ETHNIC GROUPS THAT MAKE UP THE US POPULATION WERE NOT INCLUDED, AND THE VARIABLES STUDIED IN THE UKPDS DID NOT INCLUDE ANY BEHAVIORAL DATA. LONG TERM, LONGITUDINAL PATIENT DATA ON DIABETES OUTCOMES IS COSTLY TO COLLECT AND ALL INFORMATION ON THE UKPDS OUTCOMES MODELS HAS BEEN TRANSPARENTLY REPORTED AND MADE PUBLICLY AVAILABLE. THIS HAS LEFT THE UKPDS RISK MODELS AS THE BEST OPTION FOR MANY RISK ENGINES, DESPITE THE SMALL, DATED AND NONDIVERSE SAMPLE THAT IT IS BASED ON. CAPITALIZING ON KAISER PERMANENTE SOUTHERN CALIFORNIA (KPSC) ELECTRONIC HEALTH RECORDS (EHR) DATA AND LEGACY DATA SYSTEMS, WE IDENTIFIED OVER 527,000 PATIENTS WITH INCIDENT DIABETES THAT WERE DIAGNOSED AND TREATED AT KPSC FROM 1993 TO 2020. OUR SAMPLE PROVIDES MORE THAN 4.4 MILLION PERSON-YEARS OF FOLLOW UP. MORE THAN 34,000 PATIENTS COULD BE FOLLOWED UP FOR 21 OR MORE YEARS. THE INCIDENT DIABETES COHORT FROM KPSC IS 34.4% HISPANIC, 10.6% ASIAN AND 12.7% AFRICAN AMERICAN OR BLACK ALLOWING US TO UPDATE THE RISK EQUATIONS FOR ALL UKPDS OUTCOME MODELS BY MAJOR RACE-ETHNICITY GROUPS DIRECTLY RELEVANT FOR THE U.S POPULATION. THESE UPDATED MODELS WILL ALLOW US TO IDENTIFY DISPARITIES IN DIABETES, ASSURE STATISTICAL FAIRNESS, AND IMPROVE PREDICTION OF DIABETES OUTCOMES FOR DIVERSE POPULATION GROUPS. BECAUSE DIABETES OUTCOMES ARE LARGELY INFLUENCED BY HEALTH BEHAVIORS, WE WILL ALSO ANALYZE BEHAVIORAL DATA CAPTURED IN THE EHR INCLUDING DATA ON EXERCISE AND REFERRALS TO DIABETES AND WEIGHT MANAGEMENT EDUCATION CLASSES. WE WILL USE CUTTING EDGE PARAMETRIC, SEMI-PARAMETRIC AND NON-PARAMETRIC MODELS TO RE- ESTIMATE RISK EQUATIONS USING STANDARD SPLIT SAMPLE CROSS-VALIDATION. WE WILL REPORT OUR METHODOLOGY AND RESULTS TRANSPARENTLY IN THE SAME FORMAT AS THE UKPDS. OUR STUDY WILL HELP TO UPDATE EXISTING SIMULATION MODELS AND SUPPORT MORE TIMELY AND EQUITABLE CLINICAL DECISION SUPPORT AND PATIENT EDUCATION.

ENCOURAGING MAIL ORDER PHARMACY USE TO IMPROVE OUTCOMES AND REDUCE DISPARITIES

LACTATION AND INCIDENCE OF DIABETES MELLITUS IN CARDIA WOMEN

CBT-INSOMNIA AUGMENTING USUAL CARE SSRIS TO IMPROVE YOUTH DEPRESSION OUTCOMES

COVID-19 VACCINE EFFECTIVENESS IN PREGNANT WOMEN AND THEIR INFANTS - ABSTRACT: CORONAVIRUS DISEASE 2019 (COVID-19) IS CAUSED BY SEVERE ACUTE RESPIRATORY DISTRESS SYNDROME CORONAVIRUS 2 (SARS-COV-2) WHICH EMERGED IN DECEMBER 2019 AND HAS SINCE LED TO AN UNPRECEDENTED GLOBAL PANDEMIC WITH HIGH MORBIDITY AND MORTALITY. CURRENT AUTHORIZED VACCINES AGAINST SARS-COV-2 DEMONSTRATED 70 – 95% EFFICACY IN CLINICAL TRIALS, BUT THE PIVOTAL EFFICACY TRIALS ON WHICH THE EMERGENCY USE AUTHORIZATIONS ARE BASED DID NOT INCLUDE PREGNANT WOMEN. THUS, IN THE MIDST OF A MASSIVE VACCINATION CAMPAIGN, COVID-19 VACCINE EFFECTIVENESS IN PREGNANT WOMEN AND THEIR INFANTS IS UNKNOWN. PREGNANT WOMEN ARE AT INCREASED RISK OF COVID-19 INFECTION AND HOSPITALIZATION, BUT CURRENTLY THERE IS NO STRONG RECOMMENDATION FOR OR AGAINST COVID-19 VACCINATION DURING PREGNANCY. ADDITIONALLY, COVID-19 VACCINE UPTAKE AMONG PREGNANT WOMEN AND FACTORS ASSOCIATED WITH BEING VACCINATED OR UNVACCINATED ARE UNKNOWN. WE PROPOSE TO 1) ESTIMATE COVID-19 VACCINE EFFECTIVENESS FOR PREVENTING LABORATORY-CONFIRMED COVID-19 INFECTION OR COVID-19 HOSPITALIZATION IN PREGNANT WOMEN, 2) DETERMINE EFFECTIVENESS OF COVID-19 VACCINATION DURING PREGNANCY IN PREVENTING COVID-19 INFECTION OR HOSPITALIZATION AMONG INFANTS DURING THE FIRST YEAR OF LIFE; AND DETERMINE WHETHER EFFECTIVENESS VARIES BY TRIMESTER OF VACCINATION AND 3) ESTIMATE COVID-19 VACCINATION RATES AMONG PREGNANT WOMEN OVER TIME AND AMONG UNVACCINATED PREGNANT WOMEN, IDENTIFY SOCIODEMOGRAPHIC, GEOGRAPHIC CLUSTERS AND HEALTHCARE UTILIZATION PATTERNS ASSOCIATED WITH BEING UNVACCINATED. WE ARE WELL-POSITIONED AT KAISER PERMANENTE NORTHERN CALIFORNIA, A LARGE INTEGRATED HEALTHCARE SYSTEM WITH STABLE, DIVERSE MEMBERSHIP AND COMPREHENSIVE LONGITUDINAL ELECTRONIC HEALTH RECORDS (EHR), TO ADDRESS THE RESEARCH AIMS. BY USING EHR DATA, THE STUDY WILL BE COST EFFECTIVE AND TIMELY; PROVIDING INFORMATION ON COVID- 19 VACCINE EFFECTIVENESS AMONG PREGNANT WOMEN AND ASSESSING WHETHER MATERNAL VACCINATION PROVIDES PROTECTION FOR THEIR INFANTS WHO ARE CURRENTLY INELIGIBLE TO RECEIVE COVID-19 VACCINE. THE PROPOSED RESEARCH CAN LEAD TO EVIDENCE-BASED RECOMMENDATIONS REGARDING COVID-19 VACCINATION IN PREGNANT WOMEN AND WILL PROVIDE CRITICAL INFORMATION REGARDING CHARACTERISTICS OF UNVACCINATED PREGNANT WOMEN THAT WILL BE NECESSARY FOR FUTURE DEVELOPMENT OF TARGETED INTERVENTIONS TO IMPROVE VACCINE COVERAGE AMONG PREGNANT WOMEN.

PRIMARY PREVENTION TO REDUCE CARDIOVASCULAR MORBIDITY AND OPTIMIZE CANCER OUTCOMES - PROJECT SUMMARY OUR OVERARCHING GOAL IS TO IDENTIFY AND CHARACTERIZE CANCER PATIENTS AT RISK OF DEVELOPING CANCER TREATMENT- RELATED CARDIOTOXICITY AND TO MITIGATE CARDIOVASCULAR DYSFUNCTION WHILE OPTIMIZING CANCER OUTCOMES. ADVANCES IN EARLY DETECTION AND TREATMENT OF CANCER HAS IMPROVED 5-YEAR SURVIVAL. HOWEVER, MULTI-MODAL CANCER TREATMENT OFTEN LEADS TO CARDIOTOXICITY. CARDIOVASCULAR DISEASE (CVD) EVENTS DURING TREATMENT CAN INTERFERE WITH ITS DELIVERY AND THUS LEAD TO SUB-OPTIMAL CANCER OUTCOMES AND INCREASED DOWNSTREAM MORBIDITY, COST, AND MORTALITY. AMERICAN HEART ASSOCIATION (2019) GUIDELINES RECOMMEND PRIMARY PREVENTION WITH ANTI- HYPERLIPIDEMIC AND ANTI-HYPERTENSIVE MEDICATION IN HIGH-RISK INDIVIDUALS, BASED ON ATHEROSCLEROTIC CARDIOVASCULAR DISEASE (ASCVD) RISK. HOWEVER, IT’S UNCERTAIN IF PRIMARY PREVENTION IN CANCER PATIENTS IMPROVES LONG-TERM CVD OUTCOMES. AMERICAN SOCIETY OF CLINICAL ONCOLOGY (ASCO) (2017) GUIDELINES HAS CATEGORIZED HIGH-DOSE ANTHRACYCLINES, TARGETED THERAPY, AND CERTAIN COMBINATIONS OF THESE, AS CARDIOTOXIC REGIMENS. THE IMPACT OF PRIMARY PREVENTION IN PATIENTS ON SUCH CARDIOTOXIC REGIMENS IS UNKNOWN. TO EVALUATE THESE QUESTIONS, WE WILL CREATE A UNIQUE DATASET BY MERGING KAISER PERMANENTE (KP)’S ELECTRONIC MEDICAL RECORDS WITH KP’S SEER CANCER REGISTRY, KP’S MEDICAL FINANCIAL ASSISTANCE PROGRAM, AND SOCIAL SECURITY ADMINISTRATION’S SUPPLEMENTAL INCOME, DISABILITY, AND MORTALITY DATA, IN A COHORT OF 17,000+ BREAST CANCER PATIENTS FOLLOWED LONGITUDINALLY FOR 5+YEARS. WE WILL RISK STRATIFY BREAST CANCER PATIENTS ON ASCVD RISK AND EVALUATE THE EFFECT OF PRIMARY PREVENTION USING ADVANCED CAUSAL INFERENCE MODELS EXPLORING TREATMENT EFFECT HETEROGENEITY FROM POLICY AND DECISION-MAKING PERSPECTIVES. THE STUDY AIMS ARE AIM 1: COMPARE EFFECTIVENESS OF PRIMARY PREVENTION PHARMACOLOGICAL THERAPY ON 1) CANCER AND CVD OUTCOMES DURING CHEMOTHERAPY AND 2) CANCER AND CVD OUTCOMES POST- CHEMOTHERAPY IN ADULTS WITH BREAST CANCER. AIM 2: EVALUATE THE IMPACT OF PRIMARY PREVENTION PHARMACOLOGICAL THERAPY ON FINANCIAL TOXICITY AND DISABILITY IN ADULTS WITH BREAST CANCER. AIM 3: EVALUATE THE INCREMENTAL MEDICAL EXPENDITURE AND COST-EFFECTIVENESS OF PRIMARY PREVENTION PHARMACOLOGICAL THERAPY IN ADULTS WITH BREAST CANCER USING A NET-BENEFIT REGRESSION FRAMEWORK. COMPLETION OF THIS PROPOSAL WILL ANSWER CRUCIAL QUESTIONS TO IMPROVE PATIENT OUTCOMES (1) DOES PRIMARY PREVENTION PREVENT FUTURE CVD EVENTS, IMPROVE/OPTIMIZE CANCER TREATMENT AND OUTCOMES, REDUCE FINANCIAL TOXICITY, DISABILITY, AND COST? (2) HOW MANY PATIENTS NEED TO BE TREATED TO AVOID ONE ADVERSE CARDIOVASCULAR OR CANCER OUTCOME? (2) WHAT ARE THE LONG-TERM EFFECTS OF PRIMARY PREVENTION? (3) IS PRIMARY PREVENTION COST-EFFECTIVE OR SHOULD SOCIETY INVEST ITS RESOURCES ELSEWHERE?

MOVING TO HEALTH: HOW CHANGING BUILT ENVIRONMENTS IMPACT WEIGHT AND GLYCEMIC CONTROL

A RISK-VARYING AND PERTURBED SELF-CONTROLLED CASE SERIES DESIGN FOR ASSESSING THE SAFETY OF COVID-19 VACCINES IN A LARGE HEALTH CARE SYSTEM - PROJECT SUMMARY/ABSTRACT DESPITE THE SUCCESS OF THE UNPRECEDENTED COVID-19 VACCINE ROLLOUT IN THE U.S., VACCINE HESITANCY IS EVIDENT, PARTLY DUE TO SAFETY CONCERNS ABOUT SEVERE ADVERSE EVENTS (SAES) SURROUNDING THE NOVEL TECHNOLOGY OF MRNA COVID-19 VACCINES AND REPORTS OF BLOOD CLOTS FOLLOWING RECEIPT OF THE JANSSEN COVID-19 VACCINE. WHILE RIGOROUS SAFETY MONITORING MAY HELP SUPPORT COVID-19 VACCINATION, IT IS METHODOLOGICALLY CHALLENGING TO THOROUGHLY EVALUATE THE SAFETY OF THE TWO-DOSE MRNA COVID-19 VACCINES AND THE ONE-DOSE JANSSEN COVID- 19 VACCINE. EXISTING APPROACHES CAN PRODUCE FALSE POSITIVE AND FALSE NEGATIVE SIGNALS WHEN 1) RISK WINDOWS AFTER VACCINATION ARE INCORRECTLY SPECIFIED, 2) A CONSTANT RISK OF SAES DURING THE RISK WINDOW IS WRONGLY ASSUMED, 3) FACTORS THAT MAY INFLUENCE RECEIPT OF THE SECOND DOSE OF MRNA COVID-19 VACCINES ARE NOT ACCOUNTED FOR, AND 4) THE NATURE OF THE RISK OF SAES DURING POTENTIAL OVERLAPPING RISK WINDOWS OF THE FIRST AND SECOND DOSES OF MRNA COVID-19 VACCINES IS NOT ASSESSED. IN RESPONSE TO THE FOA, PA-18-873, THIS PROPOSAL ADDRESSES THE SPECIFIC OBJECTIVE: “CREATION/EVALUATION OF STATISTICAL METHODOLOGIES FOR ANALYZING DATA ON VACCINE SAFETY, INCLUDING DATA AVAILABLE FROM EXISTING DATA SOURCES SUCH AS PASSIVE REPORTING SYSTEMS OR HEALTHCARE DATABASES.” WE PROPOSE TO DEVELOP NOVEL STATISTICAL MODELS TO PROPERLY MEASURE THE RISK OF NEW COVID-19 VACCINES BY ALLOWING THE RISK LEVEL TO VARY DURING UNKNOWN RISK WINDOWS AND USING A DATA-DRIVEN APPROACH TO DEFINE THESE RISK WINDOWS. WE WILL ALSO CREATE A NEW METRIC FOR MEASURING THE RISK OF SAES CONSIDERING BOTH THE RISK LEVEL AND THE LENGTH OF THE RISK WINDOW, ADDRESS THE POTENTIAL OVERLAP OF RISK WINDOWS OF TWO DOSES, AND EMPLOY A PROPENSITY SCORE MODEL APPROACH TO ACCOUNT FOR FACTORS THAT MAY INFLUENCE RECEIPT OF THE SECOND DOSE OF MRNA COVID-19 VACCINES. WE WILL ESTABLISH THESE NOVEL APPROACHES TO EVALUATE COVID-19 VACCINE SAFETY AND WILL APPLY THEM TO EXISTING DATA FROM MEMBERS OF KAISER PERMANENTE SOUTHERN CALIFORNIA, A LARGE, RACIALLY, AND SOCIO-ECONOMICALLY DIVERSE POPULATION. THROUGH THIS RESEARCH, WE WILL DETECT SAES OF CONCERN, BETTER INFORM THE PUBLIC AND POLICYMAKERS ABOUT THE SAFETY OF COVID-19 VACCINES, AND GENERATE VACCINE SAFETY INFORMATION THAT MAY BE HELPFUL FOR CLINICIANS TO DELIVER APPROPRIATE CARE TO THOSE AT RISK.

LONG-TERM BENEFITS AND RISKS OF BARIATRIC SURGERY IN INTEGRATED CARE SYSTEMS

PREGNANCY-RELATED RISK FACTORS AND GLUCOSE INTOLERANCE IN WOMEN DURING MIDLIFE

UNDERSTANDING FAMILY ECONOMIC IMPACT OF CHRONIC CHILD HEALTH CONDITIONS

LEVERAGING TUMOR REGISTRIES AND PATHOLOGY SPECIMENS TO FACILITATE GENETIC TESTING AND TRACEBACK FOR OVARIAN CANCER

PEDIATRIC HOSPITAL CARE IMPROVEMENT PROJECT

PRAGMATIC CLINICAL TRIAL OF CONTINUOUS GLUCOSE MONITORING-BASED INTERVENTIONS FOR SAFE INSULIN PRESCRIBING IN HIGH-RISK OLDER PATIENTS WITH TYPE 2 DIABETES - ABSTRACT HYPOGLYCEMIA IS A COMMON AND PREVENTABLE COMPLICATION OF INSULIN TREATMENT IN TYPE 2 DIABETES (T2D) THAT INCREASES DRAMATICALLY WITH AGE. IN OLDER ADULTS (AGE = 75), HYPOGLYCEMIA ACCOUNTS FOR 20% OF ALL EMERGENCY DEPARTMENT ADMISSIONS FOR ADVERSE DRUG EVENTS (PRIMARILY DUE TO INSULIN). HYPOGLYCEMIC EPISODES IN OLDER ADULTS ARE ALSO ASSOCIATED WITH INCREASED INCIDENCE OF FALL-RELATED FRACTURES, CARDIOVASCULAR EVENTS, COGNITIVE DECLINE AND DEMENTIA, HOSPITALIZATION, WORSE SELF-REPORTED QUALITY OF LIFE, AND MORTALITY. FOR PATIENTS WITH T2D REQUIRING INSULIN, OPTIMAL DOSING REQUIRES MONITORING GLUCOSE LEVELS AND DIRECTIONAL TRENDS IN THE CONTEXT OF INSULIN TYPE AND DOSE, DIET, PHYSICAL ACTIVITY, HEALTH STATUS, AND SYMPTOMS. SEVERE HYPOGLYCEMIA CAN OCCUR AT ANY TIME WHEN THE INSULIN REGIMEN DOES NOT MATCH THE CORRESPONDING PATIENT NEEDS. IN OLDER PATIENTS, FREQUENT SELF-MONITORING OF BLOOD GLUCOSE (SMBG) USING TRADITIONAL FINGERSTICK CHECKS ARE OFTEN NOT PHYSICALLY POSSIBLE (NOR DESIRABLE). MOREOVER, MANY OLDER PATIENTS WITH LONG DURATION T2D HAVE HYPOGLYCEMIA UNAWARENESS (A POTENT RISK FACTOR FOR SEVERE HYPOGLYCEMIA) AND/OR FEAR OF HYPOGLYCEMIA (WITH CORRESPONDING RELUCTANCE TO INJECT FULL INSULIN DOSE). THE OVERARCHING GOAL OF THIS R01 RESEARCH PROPOSAL IS TO SUPPORT SAFER MANAGEMENT OF INSULIN-REQUIRING, OLDER ADULTS (AGE = 75) WITH T2D AT HIGH RISK OF SEVERE HYPOGLYCEMIA. WE WILL TEST THE HYPOTHESIS THAT IN THESE HIGH-RISK OLDER ADULTS WITH T2D, A GROUP-BASED EDUCATIONAL PROGRAM THAT INCORPORATES ALARM- ENABLED CONTINUOUS GLUCOSE MONITORING (CGM) WILL REDUCE THE INCIDENCE OF SEVERE HYPOGLYCEMIA AS DEFINED BY THE AMERICAN DIABETES ASSOCIATION AS REQUIRING ACTIVE ASSISTANCE FROM ANOTHER PERSON TO ADMINISTER RESUSCITATIVE MEASURES. AIM 1: WE WILL CONDUCT A 3-ARM RANDOMIZED, PRAGMATIC CLINICAL TRIAL DESIGNED TO TEST THE EFFICACY OF TWO INTERVENTION STRATEGIES, ARM 1 – PATIENT-ONLY AND ARM 2 - PATIENT + PHARMACIST COMPARED TO ARM 3 – USUAL CARE WITHIN A LARGE, INTEGRATED CARE DELIVERY SYSTEM (KAISER PERMANENTE NORTHERN CALIFORNIA). THIS 3-ARM DESIGN ALLOWS US TO EXAMINE THE IMPACT OF TWO VERSIONS OF CGM-BASED PROGRAM IMPLEMENTATION THAT REQUIRE DIFFERENT LEVELS OF HEALTH SYSTEM INVESTMENT (I.E., PATIENT-EDUCATION AND TRAINING WITH OR WITHOUT ADDED CLINICAL PERSONNEL). AIM 2: WE WILL ALSO EXAMINE HETEROGENEITY OF INTERVENTION TREATMENT EFFECTS BY CLINICAL CONTEXT (BASELINE GLYCEMIC CONTROL, CONCURRENT COMORBIDITY) AND PATIENT CONTEXT (AGE, HEALTH LITERACY) TO INFORM FUTURE ADAPTATION AND DISSEMINATION STRATEGIES. THIS SAFETY-ORIENTED INTERVENTION STRATEGY INCORPORATING ALARM-ENABLED CGM PROVIDES THE POTENTIAL FOR A LOW-BURDEN APPROACH TO HELPING HIGH-RISK PATIENTS REDUCE INCIDENCE OF SEVERE HYPOGLYCEMIA. IF SUCCESSFUL, THE RCT EVIDENCE FROM THIS STUDY WILL SUPPORT NEW MODELS OF CARE DESIGNED TO IMPROVE PATIENT SAFETY AND PATIENT-CENTERED OUTCOMES FOR OLDER ADULTS WITH T2D.

EFFECTIVENESS OF GASTRIC SLEEVE VS. GASTRIC BYPASS FOR CARDIOVASCULAR DISEASE

AN ELECTRONIC HEALTH RECORD-BASED TOOL TO IDENTIFY NEWLY DIAGNOSED BREAST CANCER PATIENTS AT RISK OF LOW SOCIAL SUPPORT

PREDICTORS OF CVD AMONG BREAST CANCER SURVIVORS IN AN INTEGRATED HEALTH SYSTEM

MODES OF CANNABIS ADMINISTRATION AND POLYSUBSTANCE USE AMONG WOMEN BEFORE AND DURING PREGNANCY - PROJECT SUMMARY/ABSTRACT IMPORTANCE OF THE PROPOSED RESEARCH. PRENATAL CANNABIS USE IS INCREASINGLY COMMON AND COULD HAVE LARGESCALE NEGATIVE IMPACTS ON MATERNAL AND FETAL HEALTH. LEGALIZATION OF CANNABIS HAS LED TO THE PROLIFERATION OF NEW CANNABIS PRODUCTS WITH VARIOUS MODES OF ADMINISTRATION (E.G., VAPING, EDIBLES, DABBING BLUNTS) THAT DIFFER BY THC POTENCY AND SECONDARY EXPOSURES (E.G., NICOTINE, CHEMICALS FROM VAPING). YET, WE KNOW LITTLE ABOUT HOW WOMEN USE CANNABIS PRE- AND DURING PREGNANCY, WHETHER MODES VARY WITH SOCIO-DEMOGRAPHICS OR LOCAL CANNABIS POLICIES, OR HOW MODES RELATE TO CANNABIS USE FREQUENCY, CANNABIS USE DISORDER (CUD), POLYSUBSTANCE USE, QUITTING USE IN PREGNANCY, OR ADVERSE HEALTH OUTCOMES. TO FILL THIS IMPORTANT GAP IN THE LITERATURE, WE WILL CONDUCT AN INNOVATIVE MIXED-METHODS STUDY OF ~310,000 RACIALLY AND ETHNICALLY DIVERSE PREGNANCIES WITHIN KAISER PERMANENTE NORTHERN CA (KPNC) FROM 2021 TO 2026, WHERE PATIENTS ARE UNIVERSALLY SCREENED FOR SUBSTANCE USE AS PART OF STANDARD PRENATAL CARE VIA SELF-REPORT AND URINE TOXICOLOGY TESTING. USING RICH ELECTRONIC HEALTH RECORD DATA AND CANNABIS RETAILER AND POLICY DATA, OUR STUDY WILL EXAMINE SOCIO- DEMOGRAPHIC AND POLICY CORRELATES OF MODES OF USE PRE- AND DURING PREGNANCY AND TEST HOW MODES RELATE TO THE RISK OF DAILY USE, CUD, POLYSUBSTANCE USE, SUBSTANCE USE DISORDERS (SUD), QUITTING PRE- OR DURING PREGNANCY, ADDICTION TREATMENT, AND CANNABIS-RELATED PSYCHIATRIC AND MEDICAL OUTCOMES. WITH A FOCUS ON DISPARITIES, WE WILL ALSO EXAMINE DIFFERENCES IN KEY ASSOCIATIONS BY SOCIO-DEMOGRAPHIC FACTORS AND TEST WHETHER SOCIO-DEMOGRAPHIC DIFFERENCES IN CONTINUED CANNABIS USE DURING PREGNANCY ARE MEDIATED BY DIFFERENCES IN MODES OF ADMINISTRATION. TO GAIN FURTHER CLINICAL INSIGHT AND GUIDE NEXT STEPS, WE WILL CONDUCT INTERVIEWS WITH PREGNANT WOMEN WHO USED CANNABIS BEFORE AND/OR DURING PREGNANCY TO UNDERSTAND FACTORS INFLUENCING MODE CHOICE, PERCEIVED BENEFITS/HARMS OF DIFFERENT MODES, CHANGES IN MODES DURING PREGNANCY, AND EXPERIENCES WITH QUITTING. FINDINGS WILL HAVE IMMEDIATE PUBLIC HEALTH AND CLINICAL IMPLICATIONS, PROVIDING CRITICAL INFORMATION ABOUT THE DIVERSE WAYS IN WHICH WOMEN ADMINISTER CANNABIS THAT COULD SHIFT RESEARCH AND CLINICAL PRACTICE PARADIGMS. RESULTS WILL ALSO PROVIDE IMPORTANT DATA ON WHETHER LOCAL REGULATORY PRACTICES (E.G., CANNABIS RETAILER DENSITY, RESTRICTIVENESS OF LOCAL POLICIES, WARNINGS ON PRENATAL USE) ARE ASSOCIATED WITH VARIATION IN PATTERNS OF MODES OF CANNABIS USE, INFORMING THE DEVELOPMENT OF FUTURE REGULATIONS THROUGHOUT THE US. FINALLY, THIS UNIQUE STUDY COHORT WILL BE A RICH RESOURCE FOR FUTURE RESEARCH ON THE IMPACT OF DIFFERENT MODES OF CANNABIS ADMINISTRATION ON FETAL AND NEONATAL OUTCOMES.

PRENATAL SSRI EXPOSURE, MATERNAL AND CHILD GENOTYPE, AND AUTISM SPECTRUM DISORDERS

IMPLEMENTATION OF ALCOHOL SCREENING AND BRIEF INTERVENTION IN A HEALTH SYSTEM: SUSTAINABILITY, FIDELITY AND PATIENT OUTCOMES

VIRTUAL SBIRT FOR PEDIATRIC PRIMARY CARE: INCREASING ACCESS TO SCREENING, BRIEF INTERVENTION AND REFERRAL TO TREATMENT FOR ALCOHOL AND OTHER DRUG USE VIA TELEHEALTH - PROJECT SUMMARY/ABSTRACT ADOLESCENT ALCOHOL AND OTHER DRUG (AOD) USE IS A MAJOR PUBLIC HEALTH CONCERN POSING SIGNIFICANT CHALLENGES TO HEALTHCARE PROVIDERS, PATIENTS AND FAMILIES. IT IS ASSOCIATED WITH COMORBID PSYCHIATRIC AND MEDICAL CONDITIONS, POOR EDUCATIONAL AND EMPLOYMENT OUTCOMES, ACCIDENTS AND INJURIES, AND AVOIDABLE HEALTH SERVICES UTILIZATION AND COSTS (E.G., EMERGENCY AND INPATIENT). EARLY AOD USE INITIATION IS ASSOCIATED WITH ALCOHOL USE DISORDERS IN ADULTHOOD. SCREENING, BRIEF INTERVENTION AND REFERRAL TO TREATMENT (SBIRT) DELIVERED IN PEDIATRIC PRIMARY CARE IS AN EFFECTIVE APPROACH TO EARLY IDENTIFICATION AND INTERVENTION AND CAN REDUCE BOTH AOD USE AND CONSEQUENCES AND CO-OCCURRING MENTAL HEALTH SYMPTOMS, YET WIDESPREAD IMPLEMENTATION IS LACKING, DUE TO A VARIETY OF BARRIERS, INCLUDING THE TIME CONSTRAINTS AND COMPETING PRIORITIES FACED BY PEDIATRICIANS AND LACK OF TRAINED STAFF. RESEARCH ON EFFICIENT AND COST-EFFECTIVE MODALITIES OF SBIRT DELIVERY IN PEDIATRIC PRIMARY CARE IS CRITICAL TO EXPANDING THE EVIDENCE BASE AND SUPPORTING BROADER IMPLEMENTATION. ACCELERATED BY THE PANDEMIC, BEHAVIORAL TELEMEDICINE APPROACHES TO ADDRESSING ADOLESCENT AOD USE AND MENTAL HEALTH PROBLEMS ARE GAINING MOMENTUM AND OFFER THE POTENTIAL TO INCREASE THE REACH AND IMPACT OF SBIRT IN PEDIATRIC PRIMARY CARE. THIS STUDY’S OBJECTIVE IS TO EXAMINE WHETHER A CENTRALIZED, VIRTUALLY DELIVERED MODALITY OF SBIRT, RAPIDLY ACCESSIBLE BY MULTIPLE PEDIATRIC PRIMARY CARE CLINICS, CAN BE COST-EFFECTIVELY IMPLEMENTED TO IMPROVE EARLY IDENTIFICATION AND TREATMENT FOR AOD AND COMORBID MENTAL HEALTH PROBLEMS AMONG ADOLESCENTS AT HIGH OR SEVERE RISK OF AOD USE DISORDER . IN THIS WHOLLY PRAGMATIC, TYPE 1 HYBRID COMPARATIVE EFFECTIVENESS IMPLEMENTATION TRIAL, SET IN A LARGE, REAL-WORLD HEALTH SYSTEM WITH A HIGHLY DIVERSE POPULATION, WE WILL RANDOMIZE 20 BUSY, GENERAL PEDIATRIC PRIMARY CARE CLINICS WITH AN ELIGIBLE POPULATION OF APPROXIMATELY 22,320 12-17 YEAR OLD ADOLESCENTS, TO ONE OF TWO INTERVENTION ARMS: 1) CLINICS WHERE BRIEF INTERVENTIONS ARE DELIVERED VIRTUALLY BY VIDEO OR TELEPHONE BY A CENTRALIZED BEHAVIORAL HEALTH CLINICIAN (CV-SBIRT ARM), OR 2) CLINICS WHERE APPOINTMENT-BASED BRIEF INTERVENTIONS ARE DELIVERED BY A BEHAVIORAL HEALTH CLINICIAN ASSIGNED TO THE CLINIC (TRADITIONAL SBIRT ARM). LICENSED BEHAVIORAL HEALTH CLINICIANS IN BOTH ARMS WILL BE TRAINED IN THE SAME EMPIRICALLY SUPPORTED SBIRT PROTOCOL, DIFFERING ONLY IN ITS MODALITY OF DELIVERY. THE SAMPLE WILL INCLUDE ALL ADOLESCENTS AGED 12 THROUGH 17 YEARS SEEN FOR A WELL VISIT, WHO ARE AT HIGH OR SEVERE RISK OF AOD USE DISORDER DEFINED AS ENDORSING MONTHLY OR MORE FREQUENT AOD USE OR ANY AOD USE AND PAST-TWO-WEEK DEPRESSIVE SYMPTOMS OR SUICIDALITY. WE WILL USE ADMINISTRATIVE AND CLINICAL DATA COLLECTED IN THE ELECTRONIC HEALTH RECORD DURING ROUTINE CARE TO COMPARE SBIRT IMPLEMENTATION (RATES OF BRIEF INTERVENTIONS AND REFERRALS), AOD AND MENTAL HEALTH OUTCOMES (USE FREQUENCY AND SYMPTOM ENDORSEMENT AND DIAGNOSES), SPECIALTY ADDICTION MEDICINE AND PSYCHIATRY TREATMENT INITIATION AND ENGAGEMENT, HEALTH SERVICES USE (INPATIENT AND EMERGENCY DEPARTMENT), AND COST-EFFECTIVENESS IN THE INTERVENTION ARMS, AT 1 AND 2 YEARS POST-SCREENING.

ROLE OF HEALTH CARE IN ADDRESSING UNHEALTHY ALCOHOL USE AND DISPARITIES AMONG AGING WOMEN - ABSTRACT UNHEALTHY ALCOHOL USE HAS INCREASED SIGNIFICANTLY AMONG AGING WOMEN, RAISING THEIR RISK OF SERIOUS ALCOHOL RELATED ADVERSE CONSEQUENCES. AT THE SAME TIME, THEY ARE LESS LIKELY THAN MEN TO ACCESS TREATMENT, AND THIS IS EXACERBATED AMONG RACIAL/ETHNIC MINORITY WOMEN. HEALTH CARE PROVIDERS AND SYSTEMS WILL FACE AN INCREASING NUMBER OF AGING WOMEN WITH ALCOHOL PROBLEMS, OFTEN WITH CO-OCCURRING HEALTH CONDITIONS THAT WOULD IMPROVE WITH REDUCED DRINKING. CURRENTLY, THERE IS LIMITED RESEARCH ON THE GROWING NEEDS OF THIS AGING POPULATION, INCLUDING ON HOW RACIAL/ETHNIC MINORITY WOMEN MAY BE DISPROPORTIONATELY IMPACTED BY UNHEALTHY ALCOHOL USE AND ON HOW TO DEVELOP EFFECTIVE INTERVENTIONS. TO UNDERSTAND THESE CRITICAL GAPS AND INFORM A HOLISTIC APPROACH TO ALCOHOL-RELATED HEALTHCARE, WE PROPOSE A MIXED-METHOD STUDY OF OVER ONE MILLION (1,298,009) AGING WOMEN (=AGE 50) IN A DIVERSE HEALTH CARE DELIVERY SYSTEM OF OVER 4.5 MILLION MEMBERS. WE LEVERAGE UNIQUE LONGITUDINAL ELECTRONIC HEALTH RECORD (EHR) DATA FROM A UNIVERSAL ALCOHOL SCREENING PROGRAM IN PRIMARY CARE, WITH AN ESTIMATED 784,794 AGING WOMEN REGULARLY SCREENED FOR UNHEALTHY ALCOHOL USE AT MULTIPLE PRIMARY CARE VISITS BETWEEN 2014-2022. WE INTEGRATE SCREENING DATA WITH A NIAAA-FUNDED ALCOHOL REGISTRY THAT CONTAINS MEDICAL AND PSYCHIATRIC DIAGNOSES, SELF-REPORT HEALTH BEHAVIORS (E.G. TOBACCO, EXERCISE, INTERPERSONAL VIOLENCE SCREENING), AND HEALTH SERVICE ENCOUNTERS ACROSS CLINICAL SETTINGS. OUR APPROACH IS GUIDED BY A CONCEPTUAL MODEL THAT INCORPORATES INTERSECTIONALITY THEORY AND THE ANDERSEN’S MODEL OF HEALTH SERVICES UTILIZATION. WE FIRST IDENTIFY TRENDS AND PREDICTORS OF UNHEALTHY ALCOHOL USE (DEFINED AS EXCEEDING GUIDELINES OR ALCOHOL USE DISORDER) AMONG AGING WOMEN OVERALL AND BY AGE AND RACE/ETHNICITY. SECOND, WE TEST WHETHER HEALTH SERVICES UTILIZATION (E.G., ROUTINE PRIMARY CARE VISITS, BRIEF ALCOHOL INTERVENTIONS, MEDICATIONS, AND ADDICTION AND/OR PSYCHIATRY TREATMENT) IS ASSOCIATED WITH REDUCTIONS IN ALCOHOL USE OVER TIME AMONG ALL AGING WOMEN WHO REPORT UNHEALTHY ALCOHOL USE AND AMONG SUBSETS WITH CO-OCCURRING HEALTH CONDITIONS (E.G., CHRONIC PAIN, DEPRESSION/ANXIETY, DIABETES AND HYPERTENSION) AND MEDICATION USE (E.G., OPIOIDS). ACROSS EACH AIM, WE EXAMINE RACIAL/ETHNIC DIFFERENCES TO IDENTIFY POTENTIAL DISPARITIES. WE USE ADVANCED CAUSAL MODELING APPROACHES TO ANALYZE HYPOTHESIZED RELATIONSHIPS, AND TO APPROPRIATELY CONTROL FOR POTENTIAL CONFOUNDING AND BIASES. FOR A DEEPER UNDERSTANDING OF THESE VULNERABLE PATIENTS’ NEEDS AND POTENTIAL BARRIERS TO CARE, WE CONDUCT QUALITATIVE INTERVIEWS WITH AGING WOMEN WHO REPORT UNHEALTHY ALCOHOL USE AND WITH PROVIDERS WHO CARE FOR THEM IN DIFFERENT MEDICAL SETTINGS (E.G. PRIMARY CARE, GERIATRICS, ADDICTION MEDICINE), WHICH WE TRIANGULATE WITH THE QUANTITATIVE DATA. FINDINGS WILL PROVIDE URGENTLY NEEDED EVIDENCE ON HOW HEALTH SERVICES CAN IMPACT UNHEALTHY ALCOHOL USE, SO THAT HEALTH CARE SYSTEMS CAN BETTER IDENTIFY AND TREAT THIS VULNERABLE POPULATION THROUGH TARGETED INTERVENTIONS.

ASSESSING THE SAFETY AND EFFECTIVENESS OF OPIOID TAPERING IN LARGE HEALTH SYSTEMS

DOES FREE MEDICINES COVERAGE IMPROVE DIABETES SELF-CARE AND OUTCOMES FOR DIVERSE POPULATIONS?

CULTURALLY COMPETENT BEHAVIORAL INTERVENTION FOR DIABETES RISK REDUCTION

PARTICIPATORY RESEARCH TO ADVANCE COLON CANCER PREVENTION

MATTRACK: THE IMPACT OF PRECONCEPTION MATERNAL WEIGHT TRAJECTORIES ON MATERNAL, PREGNANCY, AND CHILD OUTCOMES - PROJECT SUMMARY/ABSTRACT: ELEVATED BODY MASS INDEX (BMI) AT PREGNANCY ONSET AND EXCESSIVE GESTATIONAL WEIGHT GAIN (GWG) ARE CONSISTENTLY ASSOCIATED WITH ADVERSE PREGNANCY AND CHILD OUTCOMES. DIET AND LIFESTYLE INTERVENTIONS DURING PREGNANCY HAVE HAD LIMITED SUCCESS IN REDUCING GWG OR POSTPARTUM WEIGHT RETENTION (PPWR), WITH NO IMPROVEMENT IN PERINATAL OR CHILDHOOD OUTCOMES. THEREFORE, MULTIPLE ORGANIZATIONS RECOMMEND THAT WOMEN ATTAIN A HEALTHY WEIGHT BEFORE PREGNANCY. HOWEVER, THE BENEFIT AND RISKS FOR MOTHER AND CHILD EXTENDING BEYOND DELIVERY, OPTIMAL TIMING OF PRECONCEPTION WEIGHT CHANGE, AND HOW RISKS AND BENEFITS OF PRECONCEPTION WEIGHT LOSS DIFFER ACROSS CLINICAL SUBGROUPS ARE CURRENTLY UNKNOWN. OUR PRELIMINARY DATA SUGGEST THAT THE WEIGHT TRAJECTORIES UPON WHICH WOMEN ENTER PREGNANCY (LOSS, MAINTENANCE, OR GAIN) MAY IMPACT THE HORMONAL MILIEU OF EARLY PREGNANCY AS WELL AS THE AMOUNT OF GWG AND PPWR. THE OBJECTIVE OF THIS STUDY IS TO EXAMINE THE IMPACT OF WEIGHT TRAJECTORIES IN THE IMMEDIATE PRECONCEPTION PERIOD (WITHIN 2 YEARS BEFORE PREGNANCY) ON GWG, PPWR, PREGNANCY OUTCOMES, AND CHILD GROWTH. OUR CENTRAL HYPOTHESIS IS THAT PRECONCEPTION WEIGHT CHANGE TOWARD A NORMAL BMI REDUCES RISK OF ADVERSE PREGNANCY AND BIRTH OUTCOMES BY IMPROVING PRE-PREGNANCY WEIGHT STATUS, BUT MAY INCREASE GWG, WHICH THEN INCREASES RISKS OF OUTCOMES SENSITIVE TO GWG (PPWR, LARGE FOR GESTATIONAL AGE, INFANT WEIGHT GAIN, CHILD BMI). WE FURTHER HYPOTHESIZE THAT THESE ASSOCIATIONS ARE STRONGEST AMONG WOMEN WITH MORE EXTREME BMI AND FOR MORE RAPID WEIGHT CHANGE OCCURRING CLOSER TO PREGNANCY. TO TEST THIS HYPOTHESIS, WE WILL LEVERAGE A TRANSCONTINENTAL CLINICAL DATA WAREHOUSE SPANNING ALMOST 20 YEARS WITH THE WEIGHT AND PREGNANCY DATA OF MORE THAN 130,000 RACIALLY, ETHNICALLY, AND SOCIOECONOMICALLY DIVERSE WOMEN, AND WEIGHT AND LENGTH/HEIGHT DATA OF THEIR CHILDREN THROUGH AGE 3 YEARS. WE WILL DETERMINE THE RELATIONSHIP BETWEEN MATERNAL PRECONCEPTION WEIGHT TRAJECTORIES AND GWG (TOTAL AND TRIMESTER-SPECIFIC) AND PPWR AT 6 WEEKS AND 12 MONTHS POSTPARTUM, RISK OF ADVERSE PREGNANCY OUTCOMES (GESTATIONAL DIABETES, GESTATIONAL HYPERTENSION/PREECLAMPSIA, AND CESAREAN SECTION) AND CHILD OUTCOMES (PRETERM BIRTH, SIZE FOR GESTATIONAL AGE AT BIRTH, INFANT GROWTH TRAJECTORY, AND BMI AT 3 YEARS OF AGE); AND THE DEGREE TO WHICH THESE ASSOCIATIONS ARE MEDIATED BY GWG. FOR EACH AIM, WE WILL TEST THE HYPOTHESES WITHIN PRE-PREGNANCY BMI CLASSIFICATIONS, HIGH RISK CLINICAL SUBGROUPS (E.G., PRE-EXISTING DIABETES, HYPERTENSION) AND RACIAL/ETHNIC SUBGROUPS. OUR FINDINGS WILL INFORM PRECONCEPTION WEIGHT MANAGEMENT RECOMMENDATIONS AND SHAPE THE FUTURE OF PRECONCEPTION AND ANTENATAL WEIGHT MANAGEMENT RESEARCH.

LACTATION AND GLUCOSE TOLERANCE AFTER GDM PREGNANCY

HEALTH CONSEQUENCES OF WORKPLACE POLICIES/PRACTICES-CC

EFFECTIVENESS OF THE HPV VACCINE IN IMMUNOCOMPROMISED POPULATIONS - PROJECT SUMMARY/ABSTRACT IMMUNOCOMPROMISED INDIVIDUALS—SUCH AS PEOPLE WITH HIV (PWH), AUTOIMMUNE CONDITIONS, AND A HISTORY OF SOLID ORGAN OR HEMATOPOIETIC STEM CELL TRANSPLANTATION—BEAR A SIGNIFICANTLY HIGHER BURDEN OF HUMAN PAPILLOMAVIRUS (HPV)-RELATED ANOGENITAL DISEASE COMPARED WITH IMMUNOCOMPETENT PEOPLE. WHILE HPV VACCINATION OFFERS A KEY OPPORTUNITY FOR PREVENTION, STUDIES IN IMMUNOCOMPROMISED POPULATIONS HAVE PRIMARILY EVALUATED VACCINE IMMUNOGENICITY AND SAFETY. MANY OF THESE PRIOR STUDIES DEMONSTRATED REDUCED ANTIBODY SEROCONVERSION RATES AND DURATION OF IMMUNE RESPONSES FOR IMMUNOCOMPROMISED POPULATIONS COMPARED WITH THE GENERAL POPULATION. WHILE THIS MAY TRANSLATE TO ATTENUATED PROTECTION AGAINST ANOGENITAL DISEASE, ADDITIONAL STUDIES THAT DIRECTLY EVALUATE VACCINE EFFECTIVENESS (VE) ARE WARRANTED TO INFORM OPTIMAL USE OF HPV VACCINE IN THESE HIGH-RISK INDIVIDUALS. TO DATE, THERE HAVE ONLY BEEN A FEW HPV VACCINE TRIALS IN PWH EVALUATING CLINICAL DISEASE (E.G., CONDYLOMA, CERVICAL DYSPLASIA/CANCER, AND ANAL DYSPLASIA/CANCER), BUT THESE WERE LIMITED BY SAMPLE SIZE, AND NONE WERE CONDUCTED IN PEOPLE WITH NON-HIV IMMUNOCOMPROMISING CONDITIONS. TO ADDRESS THESE MAJOR KNOWLEDGE GAPS, WE PROPOSE A COHORT STUDY IN TWO INTEGRATED HEALTH SYSTEMS TO EVALUATE HPV VE FOR PREVENTING ANOGENITAL DISEASE AMONG THREE DISTINCT GROUPS OF IMMUNOCOMPROMISED PEOPLE: (AIM 1) PWH; (AIM 2) PEOPLE WITH AUTOIMMUNE CONDITIONS (I.E., SYSTEMIC LUPUS ERYTHEMATOSUS [SLE], RHEUMATOID ARTHRITIS [RA], AND INFLAMMATORY BOWEL DISEASE [IBD], EACH EVALUATED SEPARATELY); AND (AIM 3) PEOPLE WITH A SOLID ORGAN OR HEMATOPOIETIC STEM CELL TRANSPLANT HISTORY. WE WILL EVALUATE VE FOR INCIDENT DISEASE AND RECURRENT DISEASE AMONG THOSE TREATED FOR PRIOR ANOGENITAL LESIONS. WE WILL ALSO PERFORM HPV GENOTYPING ON ARCHIVED ANOGENITAL CLINICAL SPECIMENS TO ESTIMATE VE FOR CERVICAL AND ANAL DYSPLASIA/CANCER ASSOCIATED WITH VACCINE-TARGETED HPV TYPES. FINALLY, WE WILL EVALUATE VE BY KEY VACCINATION CHARACTERISTICS, INCLUDING AGE AT VACCINATION, DOSES, TIME SINCE VACCINE, VACCINE TIMING (BEFORE/AFTER IMMUNOCOMPROMISING CONDITION), AND DISEASE-SPECIFIC FACTORS (E.G., CD4 COUNT FOR AIM 1, IMMUNOSUPPRESSIVE MEDICATION USE FOR AIM 2, AND TRANSPLANT TYPE FOR AIM 3). WE ANTICIPATE COHORTS OF ~35,000 PWH, ~15,800 WITH SLE, ~25,100 WITH RA, ~34,300 WITH IBD, AND ~21,300 WITH A TRANSPLANTATION HISTORY FROM YEARS 2006-2022. WE WILL ALSO ASSEMBLE COHORTS OF 20:1 DEMOGRAPHICALLY MATCHED IMMUNOCOMPETENT PEOPLE TO ENABLE COMPARISON OF VE ESTIMATES WITH THE CORRESPONDING IMMUNOCOMPROMISED GROUPS. WE ARE UNIQUELY POSITIONED TO ADDRESS THE AIMS GIVEN THE LARGE SAMPLES, LONG-TERM MEMBERSHIP RETENTION, DETAILED ELECTRONIC HEALTH RECORDS, AND ARCHIVED TISSUE SPECIMENS. WE ANTICIPATE OUR FINDINGS WILL INFORM TAILORED HPV VACCINATION STRATEGIES FOR DIVERSE IMMUNOCOMPROMISED POPULATIONS, INCLUDING CLARIFYING POTENTIAL BOOSTING OPTIONS AND BENEFITS OF EXTENDING CATCH-UP AGES, AND WILL THEREFORE BE OF GREAT INTEREST TO GUIDELINE GROUPS, CLINICIANS, AND PATIENTS.

(PQA2) EXPLORING THE ROLE OF SARCOPENIA IN OBESITY AND BREAST CANCER SURVIVAL

PREDICTING READMISSION AFTER STROKE STUDY (PRESS)

LEARNINGS IN DIABETES PREVENTION FROM AN INTEGRATED DELIVERY SYSTEM

LIFESTYLE AND MOLECULAR FACTORS OF BONE HEALTH IN BREAST CANCER SURVIVORS

ANTIRETROVIRAL THERAPY STRATEGIES TO LOWER CANCER RISK IN HIV-INFECTED PERSONS

FLAME RETARDANT AND ADVERSE PERINATAL OUTCOME (FRAPO)

EFFECTIVENESS OF TREATING PRENATAL DEPRESSION TO REDUCE POSTPARTUM DEPRESSION

CYP2D6 GENE VARIANTS AND EFFECTIVENESS OF ADJUVANT TAMOXIFEN IN BREAST CANCER

LIFE-COURSE AND COST TRAJECTORIES OF ALCOHOL PATIENTS: A 15-YEAR STUDY

ADULT LIFE PREDICTORS OF GENITOURINARY DISORDERS

MACHINE LEARNING TO PERSONALIZE ANTIDEPRESSANT TREATMENT - HALF OF PEOPLE STARTING ANTIDEPRESSANT MEDICATION EXPERIENCE NO SIGNIFICANT IMPROVEMENT WITH THE FIRST MEDICATION PRESCRIBED, LEADING EITHER TO DISCOURAGEMENT AND DROPOUT OR MONTHS OF TRIAL-AND-ERROR. MORE ACCURATELY MATCHING INDIVIDUALS WITH SPECIFIC MEDICATIONS COULD SIGNIFICANTLY INCREASE TREATMENT SUCCESS. WHILE SELECTING ANTIDEPRESSANT MEDICATION IS ONE OF THE MOST COMMON CLINICAL DECISIONS IN MENTAL HEALTH AND GENERAL MEDICAL CARE, ACTIONABLE EVIDENCE TO GUIDE THAT DECISION IS REMARKABLY SCARCE. MATCHING PATIENTS WITH SPECIFIC MEDICATIONS REMAINS NO BETTER THAN CHANCE. WE IDENTIFY THREE KEY GAPS IN PREVIOUS RESEARCH TO PERSONALIZE ANTIDEPRESSANT SELECTION. FIRST, PREVIOUS RESEARCH HAS NOT CLEARLY DISTINGUISHED PREDICTING OVERALL PROGNOSIS OR NONSPECIFIC RESPONSE FROM PREDICTING SPECIFIC RESPONSE TO SPECIFIC MEDICATIONS. SECOND, SAMPLE SIZES HAVE TYPICALLY BEEN INADEQUATE TO ACCURATELY DETECT DIFFERENTIAL TREATMENT RESPONSE. THIRD, PREVIOUS RESEARCH HAS FOCUSED ON RESPONSE TO A SINGLE EPISODE OF TREATMENT, AND THAT IS TOO “NOISY” A CLINICAL PHENOTYPE TO SUPPORT IDENTIFICATION OF USEFUL ENDOPHENOTYPES. WE PROPOSE TO ADDRESS THESE LIMITATIONS USING DATA RESOURCES, INFORMATICS TOOLS, AND ANALYTIC METHODS DEVELOPED BY THE NIMH-FUNDED MENTAL HEALTH RESEARCH NETWORK (MHRN). RECORDS DATABASES INCLUDE COMPREHENSIVE AND HARMONIZED DATA CONCERNING SOCIODEMOGRAPHIC CHARACTERISTICS, PAST MENTAL HEALTH DIAGNOSES AND TREATMENTS, COMORBID MENTAL HEALTH OR SUBSTANCE USE DISORDERS, CONCOMITANT TREATMENTS, DOSE AND DURATION OF ANTIDEPRESSANT EXPOSURE, AND STRUCTURED ASSESSMENT OF DEPRESSION SYMPTOMS AT BASELINE AND FOLLOW-UP. WE WILL ASSEMBLE A DATABASE INCLUDING OVER 500,000 ANTIDEPRESSANT TREATMENT EPISODES FOR OVER 200,000 PATIENTS TREATED SINCE 2010 IN ORDER TO: 1) RIGOROUSLY TEST CORE ASSUMPTIONS OF PREVIOUS RESEARCH AND TREATMENT GUIDELINES - HETEROGENEITY-OF- TREATMENT-EFFECTS ANALYSES WILL EVALUATE TWO COMMON BELIEFS REGARDING ANTIDEPRESSANT RESPONSE: A. FAVORABLE OR UNFAVORABLE PRIOR RESPONSE TO A SINGLE MEDICATION PREDICTS SUBSEQUENT RESPONSE B. PRIOR RESPONSE TO A MEDICATION IN A SPECIFIC CLASS PREDICTS SUBSEQUENT RESPONSE TO THAT CLASS 2) IDENTIFY AND VALIDATE DECISION RULES TO INFORM SELECTION OF ANTIDEPRESSANT TREATMENT BASED ON PATTERNS OF PRIOR TREATMENT RESPONSE – ANALYSES WILL USE MACHINE LEARNING METHODS (DYNAMIC WEIGHTED ORDINARY LEAST SQUARES REGRESSION) TO IDENTIFY AND VALIDATE PRACTICAL DECISION RULES FOR CLINICAL PRACTICE. 3) IDENTIFY VALID TREATMENT RESPONSE PHENOTYPES TO ENABLE FUTURE RESEARCH REGARDING GENOMIC- OR BIOMARKER-GUIDED PERSONALIZATION – PRIMARY ANALYSES WILL USE K-MEANS CLUSTERING TO IDENTIFY PATTERNS OF RESPONSE ACROSS MEDICATIONS AND MEDICATION CLASSES. ADDITIONAL ANALYSES WILL EXPLORE CLINICAL CHARACTERISTICS THAT DISTINGUISH RESPONSE PHENOTYPES AS WELL AS ORDER EFFECTS. FINDINGS WILL INFORM A NEXT GENERATION OF RESEARCH REGARDING GENETIC- AND BIOMARKER-GUIDED ANTIDEPRESSANT TREATMENT.

WEIGHT MANAGEMENT FOR IMPROVED PREGNANCY OUTCOMES