Kaiser Foundation Health Plan Inc

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.

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

CANCER RESEARCH NETWORK ACROSS HEALTH CARE SYSTEMS

MENTAL HEALTH RESEARCH NETWORK: A POPULATION-BASED APPROACH TO TRANSFORM RESEARCH

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

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

THE NORTHWEST COALITION FOR PRIMARY CARE PRACTICE SUPPORT

PROSPECTIVE STUDY OF BREAST CANCER SURVIVORSHIP

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

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

OPTIMIZING COLONOSCOPY & FECAL IMMUNOCHEMICAL TESTS FOR COMMUNITY-BASED SCREENING

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

PRAGMATIC TRIAL OF POPULATION-BASED PROGRAMS TO PREVENT SUICIDE ATTEMPT

HMORN UCSF CENTER FOR DIABETES TRANSLATIONAL RESEARCH

CLINICAL IMPLEMENTATION OF CARRIER TESTING USING NGS

COLLABORATIVE CARE FOR CHRONIC PAIN IN PRIMARY CARE

STUDYING COLORECTAL CANCER EFFECTIVENESS OF SCREENING STRATEGIES (SUCCESS)

SYSTEMS OF SUPPORT (SOS) TO INCREASE COLON CANCER SCREENING AND FOLLOW-UP

MULTIETHNIC STUDY OF BREAST ARTERIAL CALCIUM GRADATION AND CVD

PEDIATRIC RESPIRATORY ILLNESS INPATIENT MEASUREMENT SYSTEM STUDY

EVALUATING INFLUENZA, SARS-COV-2, AND OTHER RESPIRATORY VIRUS VACCINE EFFECTIVENESS IN PREVENTION OF ACUTE ILLNESS IN WASHINGTON STATE 2022-2027

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

CALIFORNIA CADDRE-SEED PHASE II

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

GENETIC DISCOVERY AND APPLICATION IN A CLINICAL SETTING CONTINUING A PARTNERSHIP

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 OF BREAST IMAGING STRATEGIES IN COMMUNITY PRACTICE

SEARCH: CANCER SCREENING EFFECTIVENESS AND RESEARCH IN COMMUNITY-BASED HEALTHCARE

CORE_PROSPECTIVE POPULATION-BASED ESTIMATION OF INFLUENZA VACCINE EFFECTIVENESS A

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

MODERATE HYPERTENSION IN PREGNANCY: SAFETY AND EFFECTIVENESS OF TREATMENT

INPATIENT TECHNOLOGY-SUPPORTED ASSISTED REFERRAL

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

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

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

MOLECULAR PROFILES AND LIFESTYLE FACTORS IN BREAST CANCER PROGNOSIS

COLLABORATIVE CARE FOR PRIMARY CARE PATIENTS WITH ALCOHOL USE DISORDERS

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

PATIENT PORTAL TO SUPPORT TREATMENT ADHERENCE

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.

MULTI-COMPONENT BEHAVIORAL INTERVENTION FOR COMPLEX PATIENTS WITH CVD RISK

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

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.

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.

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

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.

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.

DEVELOPMENT AND USE OF NETWORK INFRASTRUCTURE FOR HIGH-THROUGHPUT GWA STUDIES

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.

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

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

BODY COMPOSITION, WEIGHT, AND COLON CANCER SURVIVAL

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.

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

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

CARDIOVASCULAR DISEASE AMONG ASIANS AND PACIFIC ISLANDERS (CASPER)

PRENATAL BISPHENOL A EXPOSURE AND RISK OF GESTATIONAL DIABETES

PRE-VISIT PRIORITIZATION FOR COMPLEX PRIMARY CARE PATIENTS WITH DIABETES

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

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

COMPARISON OF CAM AND CONVENTIONAL MIND-BODY THERAPIES FOR CHRONIC BACK PAIN

ELECTIVE INDUCTION OF LABOR AND PREGNANCY OUTCOMES

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

TRANSITION TO LONG-TERM OPIOID USE AMONG OLDER ADULTS WITH CHRONIC PAIN

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.

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

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.

STATISTICAL COORDINATING CENTER FOR THE BREAST CANCER S*

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

ORAL CONTRACEPTIVE USE AND FRACTURES AROUND THE MENOPAUSAL TRANSITION

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

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.

CULTURALLY COMPETENT BEHAVIORAL INTERVENTION FOR DIABETES RISK REDUCTION

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.

ORGANIZED SELF-MANAGEMENT SUPPORT SERVICES FOR CHRONIC DEPRESSION

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

LIFESTYLE AND MOLECULAR FACTORS OF BONE HEALTH IN BREAST CANCER SURVIVORS

DOSING STUDY OF MASSAGE FOR NECK PAIN

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

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.

FEMUR FRACTURE OUTCOMES ASSOCIATED WITH BISPHOSPHONATE USE

MAXIMIZING YIELD OF THE FECAL IMMUNOCHEMICAL TEST FOR COLORECTAL CANCER SCREENING

MULTILEVEL PEER-TO-PEER EDUCATION PROGRAM TO INCREASE HPV VACCINATIONS AND WELLNESS IN SCHOOL BASED HEALTH CENTERS (PEER) - PROJECT SUMMARY/ABSTRACT: HUMAN PAPILLOMA VIRUS (HPV) INFECTION CAUSES OVER 30,000 CANCERS EACH YEAR, EVEN THOUGH MULTI-VALENT VACCINATIONS FOR HPV HAVE BEEN AVAILABLE SINCE 2006. UPTAKE OF THE VACCINE IS WELL BELOW NATIONAL TARGETS (80% BY 2030) AND VACCINATION RATES ARE NOT BEING ADMINISTERED BY THE RECOMMENDED AGE OF 13. SCHOOL BASED HEALTH CENTERS (SBHCS) ARE AN IMPORTANT SETTING WHERE MEDICALLY UNDERSERVED ADOLESCENTS CAN ACCESS PREVENTIVE HEALTH CARE SERVICES. WHILE SBHCS PROVIDE ACCESS TO HEALTH CARE, ONLY 10% OF STUDENTS ON CAMPUSES WITH SBHCS ARE USING THEIR SERVICES. COLLABORATIVE MULTILEVEL INTERVENTIONS ARE NEEDED TO INCREASE USE OF SBHCS AND IMPROVE VACCINATION UPTAKE AMONG MEDICALLY UNDERSERVED ADOLESCENTS IN THESE SETTINGS. PEER-TO-PEER EDUCATION OFFERS PROMISE IN CREATING COLLABORATIVE ENVIRONMENTS BETWEEN SBHCS AND SCHOOLS, TO INCREASE HEALTHCARE ACCESS AND IMPROVE HEALTHY BEHAVIORS. OUR PROPOSED INNOVATION, PEER, WILL TAILOR MESSAGING TO ADOLESCENTS AND PARENTS THROUGH A VALIDATED ENGAGEMENT APPROACH, BOOT CAMP TRANSLATION (AIM 1). THEN PEER WILL CONDUCT A MULTILEVEL INTERVENTIONAL STUDY THAT USES A STEPPED-WEDGE DESIGN TO TEST THE EFFECTIVENESS AND IMPLEMENTATION OF STUDENT-, PATIENT-, PROVIDER- AND SCHOOL-BASED INTERVENTIONS FOCUSED ON IMPROVING USE OF SBHCS AND UPTAKE OF HPV VACCINATION IN AGE-ELIGIBLE ADOLESCENTS (AIM 2). ANALYSIS OF MEDIATOR AND MODERATORS WILL ELUCIDATE THE MECHANISMS OF ACTION AND IDENTIFY SUBGROUPS FOR WHOM THE INTERVENTION WAS MORE AND LESS EFFECTIVE. PEER WILL BE LED BY AN EXPERIENCED TEAM OF SCIENTISTS, CLINICIANS, AND COMMUNITY ORGANIZATIONS WITH EXPERTISE IN IMPLEMENTATION SCIENCE, HPV VACCINATION RESEARCH, AND COMMUNITY ENGAGEMENT. PEER WILL ALSO BE OVERSEEN BY AN ADVISORY BOARD MADE UP OF STAKEHOLDERS INCLUDING SCHOOL ADMINISTRATION AND YOUTH. IF SUCCESSFUL, PEER COULD SIGNIFICANTLY INCREASE THE USE OF SBHCS, AND DECREASE HPV-ASSOCIATED CANCERS AND, THUS, REDUCE THE BURDEN OF CANCER IN THE UNITED STATES.

PREPARE: A RANDOMIZED TRIAL OF A PRE-PREGNANCY WEIGHT LOSS INTERVENTION

IMPACT OF BARIATRIC SURGERY ON LONG-TERM DIABETES REMISSION AND COMPLICATIONS

ORAL HEALTH 4 LIFE: PROMOTING ORAL HEALTH AMONG TOBACCO QUITLINE CALLERS

OPTIMIZING AN ONLINE MOTIVATIONAL TOBACCO CESSATION PROGRAM

MULTILEVEL DETERMINANTS OF RACIAL/ETHNIC DISPARITIES IN LUNG CANCER SCREENING UTILIZATION - ABSTRACT SINCE DECEMBER 2013, THE U.S. PREVENTIVE SERVICES TASK FORCE HAS RECOMMENDED LUNG CANCER SCREENING (LCS) WITH LOW-DOSE COMPUTED TOMOGRAPHY FOR HIGH-RISK INDIVIDUALS WITH A SMOKING HISTORY, AFFORDING A MAJOR OPPORTUNITY TO REDUCE LUNG CANCER MORTALITY, ESPECIALLY IN RACIAL/ETHNIC AND DISADVANTAGED POPULATIONS THAT ARE DISPROPORTIONATELY AFFECTED BY THE DISEASE. YET, THERE IS CONCERN THAT LCS IS NOT BEING DELIVERED EFFECTIVELY AND EQUITABLY, GIVEN ITS MANY UNIQUE IMPLEMENTATION CHALLENGES. LCS UTILIZATION REMAINS LOW. EMERGING DATA ALSO SUGGEST POORER UPTAKE OF LCS IN BLACK VERSUS WHITE INDIVIDUALS. EVEN LESS IS KNOWN ABOUT RACIAL/ETHNIC DISPARITIES IN SMOKING CESSATION, ALTHOUGH SMOKING CESSATION COUNSELING IS AN INTEGRAL COMPONENT OF THE LCS PROCESS. IDENTIFYING FACTORS ASSOCIATED WITH LCS UTILIZATION, PARTICULARLY THOSE THAT CONTRIBUTE TO RACIAL/ETHNIC DISPARITIES, IS THUS CRITICAL TO DELIVER LCS OPTIMALLY. FOLLOWING WELL-ESTABLISHED CONCEPTUAL FRAMEWORKS IN WHICH MULTIPLE LEVELS OF INFLUENCE AFFECT CANCER SCREENING BEHAVIORS, WE POSIT THAT LCS UTILIZATION IS AFFECTED BY INDIVIDUAL-, NEIGHBORHOOD-, PROVIDER-, AND HEALTH FACILITY-LEVEL FACTORS. STUDIES TO IDENTIFY MULTILEVEL FACTORS ASSOCIATED WITH LCS UTILIZATION HAVE BEEN LIMITED TO DATE, DUE IN PART TO KNOWN CONSTRAINTS IN THE DATA SOURCES AVAILABLE TO EVALUATE LCS, ESPECIALLY AT STEPS BEFORE SCREENING INITIATION. ELECTRONIC HEALTH RECORDS (EHR) ARE A RECOGNIZED BUT LARGELY UNTAPPED DATA SOURCE TO ADDRESS LCS. COMPARED TO OTHER DATA SOURCES, INTEGRATED HEALTH SYSTEM EHRS CAPTURE COMPREHENSIVE LONGITUDINAL DATA ON CLINICAL SERVICES FROM A DEFINED POPULATION, PROVIDING A ROBUST AND EFFICIENT MEANS TO INVESTIGATE MULTILEVEL DETERMINANTS OF DISPARITIES IN LCS UTILIZATION. IN OUR FOUNDATIONAL WORK USING EHR DATA TO CHARACTERIZE EARLY PATTERNS OF LCS UTILIZATION, WE FOUND EVIDENCE OF RACIAL/ETHNIC DISPARITIES IN THE PROCESS AFTER SCREENING INITIATION. IN THIS PROPOSAL, WE AIM TO IDENTIFY AND UNDERSTAND MULTILEVEL DETERMINANTS OF RACIAL/ETHNIC DISPARITIES IN LCS UTILIZATION, BEFORE AND UP THROUGH SCREENING INITIATION. SPECIFICALLY, WE WILL DETERMINE THE INFLUENCE OF FACTORS AT THE INDIVIDUAL, NEIGHBORHOOD, PROVIDER, AND FACILITY LEVELS ON DISPARITIES IN LCS UTILIZATION, STARTING FROM THE OPPORTUNITY TO BE SCREENED, AS MEASURED BY THE COMPLETENESS OF EHR DOCUMENTATION ON SMOKING HISTORY TO ASSESS LCS ELIGIBILITY (AIM 1), FOLLOWED BY LCS REFERRAL AND INITIATION (AIM 2) AND REFERRAL AND USE OF SMOKING CESSATION SERVICES (AIM 3). WE WILL COMPILE, LINK, AND ANALYZE AVAILABLE EHR, QUESTIONNAIRE, AND GEOSPATIAL DATA FROM A SOCIODEMOGRAPHICALLY DIVERSE POPULATION OF OVER 1.3 MILLION ADULTS IN AN INTEGRATED HEALTH SYSTEM FROM 2014 TO 2023. OVERALL, OUR MULTILEVEL ANALYSIS WILL GENERATE VALUABLE INSIGHT INTO THE MAJOR AND MODIFIABLE DRIVERS OF RACIAL/ETHNIC DISPARITIES AT KEY STEPS IN LCS FROM ELIGIBILITY ASSESSMENT TO SCREENING INITIATION. THESE FINDINGS WILL PROVIDE AN EMPIRICAL BASIS TO GUIDE HEALTH SYSTEMS IN DEVELOPING MULTILEVEL INTERVENTIONS THAT IMPROVE LCS OUTREACH AND UTILIZATION, BOTH EFFECTIVELY AND EQUITABLY.

BUPRENORPHINE AND SUBSTANCE ABUSE SERVICES FOR PRESCRIPTION OPIOID DEPENDENCE

SEVERE HYPOGLYCEMIA: ASCERTAINMENT, SURVEILLANCE AND PHARMACOVIGILANCE

PRECURSORS OF FIRST-EPISODE PSYCHOSIS IN A POPULATION-BASED SAMPLE

COMMONLY USED MEDICATIONS AND RISK OF COLORECTAL CANCER RECURRENCE

STUDY TO ASSESS THE INCIDENCE OF TYPE 1 DIABETES IN YOUNG ADULTS

MEASURING PATIENT EXPECTATIONS FOR CAM THERAPIES

MATERNAL AUTOANTIBODY REACTIVITY, GESTATIONAL INFLAMMATION, AND CHILD NEURODEVELOPMENT (MARGIN) - ABSTRACT APPROXIMATELY ONE IN SIX CHILDREN IN THE US IS AFFECTED BY NEURODEVELOPMENTAL DISORDERS (NDD). A WIDE RANGE OF MEDICAL AND PSYCHIATRIC CONDITIONS COMMONLY CO-OCCUR WITH NDD, IMPACTING QUALITY OF LIFE. THE CAUSES OF NDD ARE LARGELY UNKNOWN, AND FEW MODIFIABLE RISK FACTORS HAVE BEEN IDENTIFIED. A GROWING BODY OF EVIDENCE SUPPORTS A CRITICAL ROLE FOR BOTH GENETIC AND ENVIRONMENTAL FACTORS, PARTICULARLY DURING GESTATION AND THE EARLY POSTNATAL PERIOD. UNDERSTANDING THE UNDERLYING ETIOLOGY IS CRUCIAL, AS THE IDENTIFICATION OF RISK FACTORS AND THE MECHANISMS BY WHICH THEY ACT WOULD ALLOW FOR EARLIER IDENTIFICATION, TREATMENT, AND PREVENTION OF NDD AND ASSOCIATED MORBIDITY. IN OUR CURRENTLY FUNDED IMPACT STUDY (1R01HD095128), WE ARE TESTING THE HYPOTHESIS THAT MATERNAL INFLAMMATION DURING PREGNANCY STEMMING FROM IMMUNE OR METABOLIC DYSREGULATION ADVERSELY IMPACTS NEURODEVELOPMENT. WE ARE LEVERAGING THE UNIQUE RESOURCES OF THE KAISER PERMANENTE RESEARCH BIOBANK PREGNANCY COHORT TO CONDUCT A LONGITUDINAL PROSPECTIVE INVESTIGATION OF MATERNAL GESTATIONAL INFLAMMATORY CONDITIONS, IMMUNE AND METABOLIC BIOMARKERS DURING PREGNANCY, AND MATERNAL GENETICS IN RELATION TO NDD. THE GOAL OF THIS NEW APPLICATION IS TO EXTEND THE AIMS OF IMPACT TO INTERROGATE ADDITIONAL GESTATIONAL BIOMARKERS - MATERNAL AUTOANTIBODIES (MA) TO FETAL BRAIN PROTEINS - IN THE PREGNANCY BLOOD SAMPLES COLLECTED FROM THE MOTHERS OF 750 ASD, 2000 DEVELOPMENTAL DELAY (DD), AND 2000 GENERAL POPULATION (GP) CONTROL CHILDREN. OUR OVERARCHING HYPOTHESIS IS THAT MATERNAL GESTATIONAL IMMUNE/METABOLIC DYSREGULATION IS ASSOCIATED WITH THE PRESENCE OF MA DURING PREGNANCY WHICH PREDISPOSES TO ALTERED NEURODEVELOPMENT OF THE CHILD. IN AIM 1, WE WILL EXAMINE MATERNAL RISK PROFILES RELATED TO THE PRESENCE OF MA DURING PREGNANCY THAT ARE ASSOCIATED WITH NDD. IN AIM 2, WE WILL EXPLORE WHETHER MATERNAL GENETICS ARE ASSOCIATED WITH THE PRESENCE OF MA DURING PREGNANCY. IN AIM 3, WE WILL EXAMINE THE JOINT EFFECTS OF MATERNAL MA REACTIVITY AND MATERNAL CLINICAL CHARACTERISTICS, BIOMARKERS OF IMMUNE AND METABOLIC FUNCTION AND GENETIC FACTORS ON ASD AND DD, ON PHENOTYPIC SUBGROUPS OF ASD (ASD+/-INTELLECTUAL DISABILITY (ID), ASD+/- DEVELOPMENTAL REGRESSION) AND DD (LANGUAGE DELAY, MOTOR DELAY, GLOBAL DELAY, ID), AND ON CLINICAL SUBTYPES OF THE CHILD DEFINED BY COMMONLY CO-OCCURRING INFLAMMATION-MEDIATED IMMUNE AND METABOLIC CONDITIONS, AND DETERMINE IF ASSOCIATIONS DIFFER BY CHILD SEX. WE SEEK FUNDS TO ASSAY FOR MA IN THE MATERNAL PREGNANCY BIOSPECIMENS FROM THE ~2500 MOTHERS IN OUR IMPACT COHORT PLUS AN ADDITIONAL ~2250 MOTHERS AND PERFORM STATISTICAL ANALYSES TO ADDRESS OUR SPECIFIC AIMS. THIS LARGE SCALE, COMPREHENSIVE STUDY PROVIDES A FRAMEWORK TO EXPLORE RELATIONSHIPS BETWEEN MATERNAL IMMUNE DYSREGULATION AND METABOLIC FUNCTION, MATERNAL AUTOANTIBODY REACTIVITY IN THE FIRST AND SECOND TRIMESTERS, MATERNAL GENETICS, AND RISK FOR A RANGE OF NEURODEVELOPMENTAL DISORDERS IN CHILDREN. FINDINGS WILL CONTRIBUTE TO THE DEVELOPMENT OF PRENATAL AND NEWBORN SCREENING FOR ADVERSE NEURODEVELOPMENT, ULTIMATELY ENABLING EARLIER INTERVENTION AND PRIMARY PREVENTION.

MAMMOGRAPHIC DENSITY & PROGNOSIS AMONG BREAST CANCER INTRINSIC SUBTYPES

PREGRAVID BIOMARKERS OF GDM RISK FETAL GROWTH AND PROGRESSION TO DIABETES

COMPARING THE EFFECTS OF PHARMACOLOGICAL TREATMENT FOR GESTATIONAL DIABETES ON LONG-TERM MATERNAL AND CHILD HEALTH OUTCOMES - ABSTRACT GESTATIONAL DIABETES MELLITUS (GDM) IS AMONG THE MOST COMMON COMPLICATIONS OF PREGNANCY AND IT INCREASES THE RISK OF PERINATAL COMPLICATIONS AND LONG-TERM SEQUELAE FOR BOTH THE MOTHER (SUBSEQUENT DIABETES) AND THE EXPOSED CHILD (OBESITY). UP TO 50% OF PATIENTS WITH GDM REQUIRE THE ADDITION OF PHARMACOLOGIC THERAPY DURING PREGNANCY. HOWEVER, THE LONG-TERM EFFECTS OF PHARMACOLOGIC TREATMENT OF GDM ON MATERNAL AND CHILD OUTCOMES ARE UNKNOWN, MAKING THE OPTIMAL TREATMENT UNCLEAR. WE PROPOSE A LONGITUDINAL COHORT STUDY OF MORE THAN 44,000 KAISER PERMANENTE MEMBERS (>79% FROM RACIAL/ETHNIC MINORITY GROUPS) WITH TIME-VARYING EXPOSURE TO METFORMIN, GLYBURIDE, AND INSULIN DURING PREGNANCY. PREGNANCIES DIAGNOSED WITH GDM REQUIRING PHARMACOLOGIC TREATMENT FROM 2008 TO 2021 AT KAISER PERMANENTE NORTHERN AND SOUTHERN CALIFORNIA WILL BE INCLUDED. WE WILL FOLLOW PREGNANT INDIVIDUALS AND THEIR CHILDREN THROUGH OUR COMPREHENSIVE ELECTRONIC HEALTH RECORD (EHR) FOR UP TO 18 YEARS. WE WILL TAKE ADVANTAGE OF NATURAL VARIATION IN CLINICAL PRACTICE AND CHANGES OVER TIME IN PRESCRIBING PRACTICES FOR FIRST LINE MEDICAL THERAPY. THE STUDY POPULATION WILL CONSIST OF ALL PATIENTS DIAGNOSED WITH GDM WHO - AFTER DIET THERAPY - INITIATED PHARMACOTHERAPY WITHIN EITHER INSULIN, GLYBURIDE, OR METFORMIN. WE WILL USE STATE-OF-THE-ART CAUSAL AND STATISTICAL METHODS THAT CAN EMULATE INFERENCES FROM CONCEPTUAL RANDOMIZED CONTROLLED TRIALS (RCTS) USING OBSERVATIONAL DATA TO INFORM THE CHOICE OF PHARMACOLOGIC TREATMENT IN A LARGE, DIVERSE POPULATION OF ADULTS WITH GDM. THIS WILL BE ACCOMPLISHED BY CONDUCTING A SERIES OF REAL-WORLD DATA COHORT STUDIES BASED ON RETROSPECTIVE EHR DATA WITH INCLUSION/EXCLUSION CRITERIA AND START OF FOLLOW-UP THAT MIMIC THOSE OF THE RCTS EMULATED. MORE SPECIFICALLY, WE PLAN TO CONDUCT ANALYSES FOR PREGNANT INDIVIDUALS DIAGNOSED WITH GDM TO COMPARE THE EFFECTS OF STATIC AND DYNAMIC TREATMENT REGIMENS WITH GLYBURIDE, METFORMIN, AND INSULIN ON MATERNAL DIABETES RISK AFTER PREGNANCY AND CHILD GROWTH AND OBESITY RISK. THE STATIC AND DYNAMIC TREATMENT REGIMENS WILL BE SPECIFIED TO REFLECT CURRENT CLINICAL PRACTICE AND DIRECTLY INFORM DECISIONS ON, NOT ONLY, WHAT INITIAL DRUG TYPE AND DOSE TO CHOOSE, BUT ALSO, IF AND HOW TO INTENSIFY TREATMENT THROUGH INCREASED DRUG DOSE OR INITIATION OF INSULIN WHEN GLYCEMIA CONTROL IS NOT REACHED WITH AN ORAL AGENT. THE INCIDENCE OF MATERNAL DIABETES (AIM 1) AND CHILD GROWTH AND OBESITY (AIM 2) OUTCOMES WILL BE CONTRASTED BETWEEN ANY TWO STATIC OR DYNAMIC REGIMENS (E.G., SUSTAINED EXPOSURE TO INSULIN VERSUS EXPOSURE TO GLYBURIDE UNLESS GLYCEMIC CONTROL IS NOT REACHED, AT WHICH TIME INSULIN IS INITIATED). THIS STUDY WILL YIELD RESULTS IMMEDIATELY APPLICABLE TO CLINICAL PRACTICE BY PROVIDING HEAD-TO-HEAD COMPARISONS OF PHARMACOLOGIC GDM TREATMENT STRATEGIES (METFORMIN, GLYBURIDE, INSULIN) USING STATE-OF-THE-ART ANALYTIC METHODOLOGY

ROLE OF LIVER AND VISCERAL FAT IN GLUCOSE AND LIPID METABOLISM DURING PREGNANCY

COMPARATIVE EFFECTIVENESS AND SAFETY OF METABOLIC/BARIATRIC SURGERY, GLP-1, AND SGLT-2 MEDICATIONS FOR PATIENTS WITH OBESITY AND TYPE 2 DIABETES - PROJECT SUMMARY MORE THAN 12 MILLION AMERICANS CURRENTLY LIVE WITH BOTH OBESITY AND TYPE 2 DIABETES (T2D), PUTTING THEM IN ONE OF THE HIGHEST RISK GROUPS FOR DEVELOPING SERIOUS MICROVASCULAR AND MACROVASCULAR COMPLICATIONS. THE AMERI- CAN DIABETES ASSOCIATION’S CLINICAL PRACTICE GUIDELINES RECOMMEND METABOLIC/BARIATRIC SURGERY (MBS) AND/OR PHARMACOLOGIC TREATMENT OF OBESITY FOR PATIENTS WITH OBESITY AND T2D. IN PARTICULAR, GLUCAGON-LIKE PEPTIDE-1 RE- CEPTOR AGONISTS (GLP-1RAS) AND SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT2IS) HAVE BOTH DEMONSTRATED EFFICACY IN WEIGHT LOSS AND PREVENTING MICROVASCULAR AND MACROVASCULAR COMPLICATIONS AND ARE MORE ACCESSI- BLE THAN MBS. HOWEVER, THERE ARE NO LONG-TERM STUDIES COMPARING GLP-1RAS OR SGLT2IS WITH MBS HEAD-TO- HEAD WITH RESPECT TO EFFECTIVENESS AND SAFETY, OVERALL AND IN GROUPS DISPROPORTIONATELY AFFECTED BY OBESITY AND T2D BUT UNDERREPRESENTED IN CLINICAL TRIALS SUCH AS RACIAL AND ETHNIC MINORITY POPULATIONS AND RURAL RESIDENTS. THERE IS A CLEAR AND URGENT NEED FOR LARGE, REAL-WORLD COMPARATIVE EFFECTIVENESS RESEARCH STUDIES TO HELP PA- TIENTS AND THEIR CLINICIANS MAKE EVIDENCE-INFORMED DECISIONS REGARDING THE RISKS AND BENEFITS OF SURGICAL AND MEDICAL APPROACHES TO REDUCE THE LONG-TERM COMPLICATIONS OF CONCURRENT OBESITY AND T2D. WE PROPOSE A COM- PARATIVE EFFECTIVENESS AND SAFETY STUDY USING ADMINISTRATIVE CLAIMS AND LINKED ELECTRONIC HEALTH RECORD DATA ON A DIVERSE NATIONWIDE COHORT (~40% RACIAL/ETHNIC MINORITY) OF >500,000 PATIENTS WITH T2D AND OBESITY TREATED WITH MBS, GLP-1RA, OR SGLT-2I FROM 2010 TO 2025, ENCOMPASSING PATIENTS COVERED IN COMMERCIAL, MEDICARE ADVANTAGE, AND 100% OF MEDICARE FEE-FOR-SERVICE PLANS. OUR SPECIFIC AIMS WILL COMPARE THE EFFECTIVENESS OF GLP-1RAS AND SGLT-2IS VERSUS MBS IN IMPROVING METABOLIC OUTCOMES (WEIGHT, BLOOD PRESSURE, AND HEMOGLO- BIN A1C), REDUCING RATES OF MICRO- AND MACROVASCULAR DISEASE, AND ALL-CAUSE MORTALITY AMONG PATIENTS WITH OBE- SITY AND T2D. WE WILL ALSO COMPARE THE SAFETY OF GLP-1RAS AND SGLT-2IS VERSUS MBS AMONG PATIENTS WITH OBESITY AND T2D BY EXAMINING RATES OF ALL-CAUSE HOSPITALIZATIONS AND BY EXPLORING OTHER SAFETY OUTCOMES (EMERGENCY DEPARTMENT CARE, SEVERE HYPOGLYCEMIA, DIABETIC KETOACIDOSIS, HYPEROSMOLAR HYPERGLYCEMIA, ACUTE KIDNEY INJURY, AND SEVERE GENITOURINARY INFECTIONS). A PROSPECTIVE RANDOMIZED TRIAL INVESTIGATING THESE QUESTIONS WOULD BE PROHIBITIVELY EXPENSIVE AND LOGISTICALLY CHALLENGING TO CONDUCT GIVEN THE HIGH COSTS OF THESE TREAT- MENTS AND THE VERY LARGE SAMPLE SIZES NEEDED TO EXAMINE INCIDENT MICRO- AND MACROVASCULAR OUTCOMES, PAR- TICULARLY IN HIGH PRIORITY PATIENT SUBGROUPS. OUR PROPOSED STUDY WILL BE THE LARGEST AND LONGEST STUDY TO DATE COMPARING THE REAL-WORLD EFFECTIVENESS AND SAFETY OF GLP-1RA, SGLT-2I, AND MBS TO MANAGE OBESITY AND T2D WHILE ALSO GENERATING EVIDENCE FOR SUBGROUPS THAT ARE OFTEN UNDERREPRESENTED IN CLINICAL TRIALS. THE STUDY WILL PROVIDE TIMELY AND RIGOROUS COMPARATIVE EFFECTIVENESS AND SAFETY EVIDENCE TO HELP INFORM CLINICAL DECISIONS.

EVALUATION OF VALUE-BASED HEALTH PLAN DESIGN

STUDY OF OSTEOPOROTIC FRACTURES (SOF)

USING MACHINE LEARNING TO ACCELERATE OUR UNDERSTANDING OF RISKS FOR EARLY SUBSTANCE USE AMONG CHILD-WELFARE AND COMMUNITY YOUTH - PROJECT SUMMARY/ABSTRACT THE ECONOMIC TOLL OF SUBSTANCE USE/ABUSE IS ESTIMATED TO BE OVER $740 BILLION ANNUALLY AS A RESULT OF ACCIDENTS, HEALTH CARE, HOMELESSNESS, UNEMPLOYMENT, AND CRIMINAL ACTIVITY. ADOLESCENCE IS A CRITICAL TIME FOR INTERVENTION, AS 90% OF ADULTS WHO MEET THE CRITERIA FOR ADDICTION INITIATE USE OF ALCOHOL OR DRUGS IN ADOLESCENCE. YET, PREVENTION EFFORTS HAVE BEEN HINDERED BY MINIMAL SUBSTANCE USE SCREENING BY PRIMARY CARE PROVIDERS AS WELL AS LOW RATES OF DISCLOSURE BY ADOLESCENTS IN MEDICAL SETTINGS. THESE CHALLENGES NECESSITATE NEW APPROACHES TO DETECT KEY RISK FACTORS AND ENHANCE SCREENING METHODS. IMPORTANTLY, ADOLESCENTS WITH EXPERIENCES OF CHILD MALTREATMENT ARE MORE SUSCEPTIBLE TO EARLY SUBSTANCE USE AND MORE LIKELY TO PROGRESS FROM EXPERIMENTATION TO ADDICTION THAN NON-MALTREATED YOUTH. THE ACCUMULATING EVIDENCE AND OUR PRELIMINARY DATA SUGGEST THAT THE TOP PREDICTORS OF EARLY SUBSTANCE USE ARE NOT RELEVANT FOR CHILD WELFARE (CW) YOUTH, REQUIRING NEW STUDIES OF THE RELEVANT RISK FACTORS FOR THIS VULNERABLE POPULATION. THE PROPOSED STUDY ADDRESSES THESE GAPS BY USING CUTTING-EDGE MACHINE LEARNING MODELS TO PROVIDE VITAL NEW EVIDENCE REGARDING RISK FACTORS SPECIFIC TO THE CW POPULATION AS WELL AS RISKS FOR EARLY SUBSTANCE USE THAT MAY BE COMMON TO BOTH CW AND NON-CW YOUTH. WE WILL USE TWO UNIQUE DATA SOURCES TO ACCOMPLISH THIS. OUR PRIMARY DATA WILL COME FROM ELECTRONIC HEALTH RECORDS (EHR) OF KAISER PERMANENTE SOUTHERN CALIFORNIA (KPSC) MEMBERS (ESTIMATED SAMPLE SIZE OF 3.4 MILLION CHILDREN, 2007-2020). WE WILL USE DIAGNOSIS CODES FOR MALTREATMENT TO INDICATE THE CW SAMPLE, A REASONABLE ASSUMPTION OF REFERRAL TO CHILD WELFARE. RISK FACTORS WILL BE OBTAINED FROM DIAGNOSIS CODES AND ABSTRACTABLE PROGRESS NOTES IN THE EHR OF CHILDREN AND PARENTS AS WELL AS COUNTY CRIME AND GEOGRAPHIC INCOME DATA. SECOND, TO ADDRESS THE LIMITATIONS OF EHR TO CAPTURE MORE DETAILED PSYCHOSOCIAL DATA, WE WILL USE AN EXISTING LONGITUDINAL DATASET OF 454 YOUTH, 303 REFERRED FROM CHILD WELFARE AND 151 IN A COMPARISON GROUP (YAP STUDY). PARTICIPANTS WERE SEEN AT MEAN AGES 11, 13, 15, AND 18 YEARS OLD AND ARE RACIALLY/ETHNICALLY DIVERSE. COLLECTED DATA INCLUDES MEASURES OF CHILD LEVEL, PARENT LEVEL, FAMILY LEVEL, AND NEIGHBORHOOD RISK FACTORS AND CW CASE RECORDS. THESE TWO DATA SOURCES WILL ALLOW US TO: 1) PRODUCE CRITICAL NEW KNOWLEDGE REGARDING THE RELEVANT PREDICTORS OF EARLY SUBSTANCE USE FOR CW VERSUS NON-CW YOUTH AND 2) USE INTENSIVE SURVEY DATA (YAP) TO DETERMINE RISK FACTORS THAT ARE NOT CURRENTLY COLLECTED IN EHR DATA (KPSC) THAT MAY INFORM THE DEVELOPMENT OF NEW SCREENING QUESTIONS. LASTLY, OUR PREDICTIVE MODEL HAS TRANSLATIONAL POTENTIAL TO ADVANCE SCREENING METHODS FOR ADOLESCENT SUBSTANCE USE RISK IN PEDIATRIC PRIMARY CARE THROUGH THE USE OF RISK SCORES INTEGRATED INTO CLINICAL DECISION SUPPORT TOOLS. THESE FINDINGS, IF IMPLEMENTED IN CLINICAL CARE SETTINGS, WOULD ALLOW MEDICAL PROVIDERS TO MORE ACCURATELY IDENTIFY THOSE AT RISK AND TRIGGER STRATIFICATION INTO DIFFERENT TREATMENT PATHWAYS TO PREVENT SUBSTANCE ABUSE.

COMMUNITY-BASED SELF-MANAGEMENT OF HIV AND CHRONIC DISEASE

EFFECTS OF BLOOD CONSERVATION AND DONOR CHARACTERISTICS ON TRANSFUSED PATIENT OUTCOMES IN A LARGE COMMUNITY HOSPITAL NETWORK

GLYCEMIC CONTROL AND DEMENTIA: THE ROLE OF PHARMACOTHERAPY AND VASCULAR COMPLICATIONS

CHRONIC PANCREATITIS, DIABETES AND PANCREATIC CANCER: A PROSPECTIVE APPROACH

SUSTAINED IMPLEMENTATION OF PATIENT-CENTERED CARE FOR ALCOHOL MISUSE

TRAJECTORIES OF PHYSICAL ACTIVITY AND SEDENTARY TIME IN ADOLESCENT/YOUNG WOMEN

THE ROLE OF GENETIC RISK FACTORS IN KERATINOCYTE CARCINOMA SUSCEPTIBILITY

COMMONLY USED MEDICATIONS AND BREAST CANCER RECURRENCE

ELECTRONIC COMMUNICATIONS AND HOME B.P. MONITORING

MSI FLASH: AN RCT OF YOGA AND ULTRA LOW-DOSE ESTROGEN GEL FOR VASOMOTOR SYMPTOMS

REMOTE PATIENT MONITORING OF CHRONIC DISEASE IN COMMUNITY HEALTH CENTERS (REDUCE) - PROJECT SUMMARY/ABSTRACT: CLINICAL TRIAL RESEARCH HAS DEMONSTRATED THAT REMOTE PATIENT MONITORING (RPM) OF CHRONIC DISEASE STATUS CAN BE AN EFFECTIVE TOOL TO ACHIEVE BETTER CONTROL OF BLOOD PRESSURE AND BLOOD GLUCOSE FOR SOME POPULATIONS SUCH AS PARTICIPANTS IN CLINICAL TRIALS AND AFFLUENT PATIENTS. HOWEVER, LITTLE IS KNOWN THOUGH ABOUT THE EFFECTIVENESS OF RPM IN HEALTHCARE DELIVERY SETTINGS, OR IN MEDICALLY UNDERSERVED POPULATIONS. THE COVID-19 PANDEMIC HAS BROUGHT TO THE FORE THE IMPORTANT ROLE THAT RPM CAN PLAY IN ENSURING CONTINUITY OF CARE. IT ALSO HAS ILLUSTRATED THE LIMITED INFRASTRUCTURAL PREPAREDNESS OF COMMUNITY HEALTH CENTERS, WHICH PROVIDE CARE TO THE MOST MEDICALLY UNDERSERVED PATIENTS IN THE U.S., TO PROVIDE RPM TOOLS. THE PROPOSED STUDY WILL EVALUATE THE IMPLEMENTATION OF RPM TOOLS TO COMMUNITY HEALTH CENTERS FOR PATIENTS WITH HYPERTENSION AND TYPE 2 DIABETES DURING THE COVID-19 PANDEMIC. THE GOAL OF THIS STUDY IS TO EVALUATE THE BIOMEDICAL EFFECTS OF THESE RPM INTERVENTIONS, AND TO GAIN INSIGHTS INTO BARRIERS AND FACILITATORS TO IMPLEMENTATION AND ADOPTION OF THE PROGRAMS. OUR RESULTS WILL INFORM EFFORTS TO ENSURE THAT PATIENTS IN COMMUNITY HEALTH CENTERS CAN BENEFIT FROM DIGITAL RPM INTERVENTIONS AND WILL LAY THE FOUNDATION FOR LARGE-SCALE IMPLEMENTATION OF SUCH INTERVENTIONS.

SUD CARE TRANSITIONS - PROJECT SUMMARY THE PROPOSED STUDY FOCUSES ON COMPREHENSIVELY CHARACTERIZING THE PATHWAYS OF CARE UTILIZED BY PEOPLE WHO OBTAIN CARE FOR SUBSTANCE USE DISORDER (SUD) AND COMPARING THE QUALITY AND EFFECTIVENESS OF THESE CARE PATHWAYS. MANY EFFECTIVE SUD CARE PATHWAYS ARE RECOMMENDED FOR USE IN HEALTHCARE SYSTEMS. HOWEVER, PATIENTS WITH SUD OFTEN REPORT POOR CARE EXPERIENCES PARTICULARLY REGARDING TIMELY FOLLOW-UP, PROVIDER AND GENERAL SATISFACTION RATINGS, AND CARE COMMUNICATION. BECAUSE SUD CARE PATHWAYS INVOLVE TRANSITIONS ACROSS PROVIDERS AND VENUES OF CARE, ADEQUATE TREATMENT OF SUD REQUIRES COORDINATION ACROSS PROVIDERS AND SETTINGS TO ENSURE THAT UNMET NEEDS ARE ADDRESSED, AND APPROPRIATE SUD CARE IS DELIVERED. SURPRISINGLY LITTLE IS KNOWN ABOUT THE REAL-WORLD CARE PATHWAYS THAT PEOPLE ENGAGE IN ONCE THEY ARE IDENTIFIED BY A HEALTHCARE PROVIDER AS HAVING SUD. WE PROPOSE TO LEVERAGE A LARGE NOVEL DATA SOURCE FROM KAISER PERMANENTE WASHINGTON, A LARGE INTEGRATED HEALTHCARE SYSTEM IN THE NORTHWESTERN UNITED STATES. THE DATASET WILL INCLUDE ELECTRONIC HEALTHCARE RECORDS, INSURANCE CLAIMS, AND SELF-REPORTED MEASURES OF SUBSTANCE USE AND SUD SYMPTOMS. TO IDENTIFY CARE PATHWAYS, WE WILL APPLY CONTINUOUS TIME, MULTI-STATE MARKOV MODELING METHODS TO EMPIRICALLY OBSERVE THE LONGITUDINAL COURSE OF SUD CARE TRANSITIONS UNDERTAKEN BY PATIENTS OVER TIME; EACH “STATE” OR OCCURRENCE OF CARE WILL BE CHARACTERIZED BY THE INTERVENTION RECEIVED (E.G., WITHDRAWAL MANAGEMENT, PSYCHOTHERAPY, MEDICATION TREATMENT) AND SETTING OF CARE (E.G., EMERGENCY DEPARTMENT, PRIMARY CARE, BEHAVIORAL HEALTH). ADDITIONAL STATES AND MODEL PARAMETERS WILL BE USED TO CHARACTERIZE SUD CARE QUALITY, SUCH AS WAIT TIMES BETWEEN VISITS FOR SUD, CONCORDANCE WITH SUD QUALITY MEASURES, AND PREMATURE TREATMENT TERMINATION. TO COMPARE THE EFFECTIVENESS OF IDENTIFIED PATHWAYS, WE WILL EXAMINE OUTCOMES INCLUDING OVERDOSE, MORTALITY, REMISSION, AND SUBSTANCE-RELATED MEDICAL CONDITIONS. FINALLY, EMPLOYING AN EXPLORATORY QUANTITATIVE -> QUALITATIVE SAMPLING DESIGN, WE WILL PURPOSIVELY SAMPLE PATIENTS WHO ENGAGED IN THE EMPIRICALLY DERIVED PATHWAYS AND INTERVIEW THEM TO UNDERSTAND THEIR CARE EXPERIENCES; WE WILL ALSO OBSERVE AND INTERVIEW HEALTHCARE PROVIDERS TO ELUCIDATE HEALTH SYSTEM FACTORS THAT FACILITATE OR HINDER THEIR ABILITY TO LINK PATIENTS TO ADEQUATE SUD CARE. SPECIFIC AIMS ARE: (1) APPLY MULTI-STATE MARKOV MODELS TO COMPREHENSIVELY CHARACTERIZE CARE TRANSITIONS ACROSS THE FULL SPECTRUM OF SUD CARE AMONG PATIENTS WITH SUD WITHIN A LARGE INTEGRATED HEALTH SYSTEM, (2) GENERATE DATA-DRIVEN INSIGHTS TO IMPROVE CARE DELIVERY FOR SUD USING ESTIMATED MULTI-STATE MODELS, AND (3) OBSERVE AND EXPLORE PATIENT AND PROVIDER EXPERIENCES WITH CARE TRANSITIONS ACROSS COMMON CARE PATHWAYS USING QUALITATIVE RESEARCH METHODS. IMPACT: RESEARCHERS AND HEALTH CARE CONSTITUENTS DO NOT KNOW HOW TO OPTIMIZE CARE FOR SUD IN HEALTHCARE SYSTEMS. THIS STUDY WILL IDENTIFY AND COMPARE THE QUALITY AND EFFECTIVENESS OF COMMON PATHWAYS THAT PATIENTS TAKE WHEN THEY OBTAIN TREATMENT FOR SUD AND PROVIDE DECISION MAKERS WITH INFORMATION ON HOW TO BETTER ORGANIZE THE DELIVERY OF SUD CARE.

THE ROLE OF GENETIC AND NON-GENETIC FACTORS AND CAUSAL MECHANISMS UNDERLYING CATARACT SUSCEPTIBILITY FOR RISK PREDICTION - ABSTRACT AGE-RELATED CATARACT, DEFINED AS OCULAR LENS OPACITY, IS A LEADING CAUSE OF BLINDNESS WORLDWIDE. CATARACT IS ALSO ASSOCIATED WITH INJURIOUS FALLS AND INCREASED MORTALITY AND IS A SIGNIFICANT PUBLIC HEALTH PROBLEM IN THE U.S., ACCOUNTING FOR APPROXIMATELY 60% OF MEDICARE COSTS RELATED TO VISION. GIVEN THE AGING U.S. POPULATION, CATARACT SURGERY DEMAND IS EXPECTED TO DOUBLE OVER THE NEXT 25 YEARS. THUS, IT IS IMPORTANT TO UNDERSTAND THE ETIOLOGY OF CATARACT TO IDENTIFY AT-RISK PATIENTS AND DEVELOP EFFECTIVE PREVENTION STRATEGIES. RECENTLY, WE CONDUCTED A LARGE- SCALE MULTIETHNIC GENOME-WIDE ASSOCIATION STUDY (GWAS) META-ANALYSIS OF CATARACT THAT HAS IDENTIFIED 55 GENETIC LOCI, INCLUDING 38 NOVEL LOCI, THAT UNDERLIE THE RISK OF CATARACT. MAJORITY OF THE GENES IN THESE LOCI WERE INDEPENDENTLY SUPPORTED AS PROMISING CANDIDATES FOR CATARACT BY THE DATABASE ISYTE (INTEGRATED SYSTEMS TOOL FOR EYE GENE DISCOVERY), BASED ON THEIR SIGNIFICANT EXPRESSION IN THE LENS. WHILE THESE DATA UNCOVERED POTENTIAL NEW CAUSAL GENES IN THE IDENTIFIED LOCI, THEIR FUNCTION IN THE LENS IS NOT DEFINED AND THEIR ROLE UNDERLYING CATARACT RISK REMAINS LARGELY UNKNOWN. FURTHER, WHETHER CATARACT-LOCI REGULATE GENES AND HOW REGULATION DIFFERS ACROSS TISSUES HAS NOT YET BEEN EXPLORED. OUR STUDY ALSO IDENTIFIED STRONG GENETIC CORRELATIONS BETWEEN CATARACT AND SEVERAL DISORDERS/TRAITS, INCLUDING, GLAUCOMA, MYOPIA, CIGARETTES SMOKING, AND BMI, SUPPORTING PREVIOUS OBSERVATIONAL STUDIES. HOWEVER, IT IS NOT CLEAR THAT THESE ASSOCIATIONS ARE CAUSAL. FINALLY, NO PREDICTIVE TOOL EXISTS FOR EVALUATING INDIVIDUALS AT-RISK FOR CATARACT. THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO UNDERSTAND THE ROLE OF GENETIC AND NON-GENETIC FACTORS AND CAUSAL MECHANISMS UNDERLYING THE ETIOLOGY OF CATARACT AND DEVELOP A PREDICTION TOOL TO FACILITATE RISK-STRATIFIED SCREENING FOR CATARACT. BY LEVERAGING A RICH MULTIETHNIC COHORT, WITH BOTH GENOME-WIDE GENOTYPE DATA AND EXTENSIVE CLINICAL DATA COLLECTED THROUGH ELECTRONIC HEALTH RECORDS, AND USING WHOLE-EXOME SEQUENCING (WES) DATA OF UK BIOBANK PARTICIPANTS, WE WILL ACCOMPLISH THE FOLLOWING SPECIFIC AIMS: 1.A) IDENTIFY NOVEL GENETIC PREDICTORS OF CATARACT RISK USING HIGH QUALITY WES DATA AND TRANSCRIPTOME-WIDE ASSOCIATION STUDY (TWAS) APPROACH; 1.B) EVALUATE WHETHER GLAUCOMA, MYOPIC REFRACTIVE ERROR, DIABETES, HIGH BLOOD PRESSURE, HIGH BMI, CIGARETTE SMOKING, OR ALCOHOL CONSUMPTION AND OTHER CLINICAL AND BEHAVIORAL FACTORS ARE CAUSAL RISK FACTORS OF CATARACT USING A MENDELIAN RANDOMIZATION APPROACH; 2) DEVELOP RISK PREDICTION MODELS OF CATARACT RISK BY INTEGRATING POLYGENIC RISK SCORES ALONG WITH OTHER RISK FACTORS; AND 3) DETERMINE THE FUNCTION – IN THE LENS USING ANIMAL MODELS – OF NOVEL CANDIDATE GENES PRIORITIZED IN CATARACT-ASSOCIATED LOCI. THIS PROPOSED RESEARCH IS SIGNIFICANT BECAUSE IT WILL FILL AN IMPORTANT GAP IN CATARACT GENETICS AND WILL PROVIDE IMPORTANT MECHANISTIC INSIGHTS INTO THE PATHOGENESIS OF CATARACT. THE PROJECT IS INNOVATIVE IN THE DEVELOPMENT OF PREDICTION MODELS OF CATARACT RISK BASED ON GENETIC AND NON-GENETIC RISK FACTORS AS WELL AS THE DEVELOPMENT OF NOVEL ANIMAL MODELS OF CATARACT. THE LONG-TERM GOAL OF THIS RESEARCH IS TO ADVANCE CATARACT ETIOLOGY KNOWLEDGE FOR EFFECTIVE INTERVENTIONS AND NON-SURGICAL THERAPEUTICS FOR ITS PREVENTION, DELAY OR TREATMENT.

INNOVATIVE METHODS TO REDUCE RACIAL AND ETHNIC DISPARITIES IN SUICIDE RISK PREDICTION - SUICIDE DEATH RATES IN THE UNITED STATES HAVE INCREASED 35% SINCE 1999. IN 2018, THERE WERE OVER 48,000 SUICIDE DEATHS, AND AN ESTIMATED 1.4 MILLION ADULTS ATTEMPTED SUICIDE. IN RESPONSE, HEALTH SYSTEMS ARE ADOPTING SUICIDE RISK PREDICTION MODELS TO GUIDE DELIVERY OF SUICIDE PREVENTION INTERVENTIONS. SUICIDE PREDICTION MODELS ESTIMATED FROM HEALTH CARE RECORDS MAY PERPETUATE CURRENT DISPARITIES IN HEALTH CARE ACCESS, QUALITY, AND OUTCOMES. SUICIDE PREDICTION MODELS MAY NOT ACCURATELY IDENTIFY HIGH-RISK PATIENTS FROM ALL RACIAL AND ETHNIC GROUPS. SUICIDE RATES VARY BY RACE AND ETHNICITY, AND BOTH THE HIGHEST AND LOWEST RATES ARE SEEN IN TRADITIONALLY UNDERSERVED POPULATIONS. SUICIDE RATES ARE HIGHEST AMONG AMERICAN INDIANS AND ALASKAN NATIVES (22.1 PER 100,000 PEOPLE) AND LOWEST IN ASIAN AND PACIFIC ISLANDER, BLACK, AND HISPANIC POPULATIONS (7.0-7.4 PER 100,000 PEOPLE) COMPARED TO 18.0 PER 100,000 PEOPLE FOR WHITE NON-HISPANICS. DIFFERENCES IN PERFORMANCE OF SUICIDE RISK PREDICTION MODELS ACROSS RACIAL AND ETHNIC SUBGROUPS HAVE THREE POSSIBLE SOURCES. FIRST, PREDICTORS OF SUICIDE RISK MAY BE MEASURED WITH ERROR, AND THIS ERROR MAY BE DIFFERENT FOR RACIAL AND ETHNIC SUBGROUPS. SECOND, SUICIDE ATTEMPTS AND DEATHS MAY BE MISCLASSIFIED, AND MISCLASSIFICATION RATES MAY DIFFER BY RACE AND ETHNICITY. THIRD, THE ASSOCIATION BETWEEN PREDICTORS AND OUTCOMES MAY VARY BY RACE AND ETHNICITY, I.E., RISK MODIFICATION. EXISTING METHODS FOR ESTIMATING PREDICTION MODELS ARE NOT DESIGNED TO ADDRESS RACIAL AND ETHNIC DISPARITIES IN PERFORMANCE. ESTIMATION PROCEDURES FOCUS ON OPTIMIZING PERFORMANCE ACROSS THE ENTIRE POPULATION, NOT WITHIN SUBGROUPS, AND PERFORMANCE IN LESS PREVALENT SUBGROUPS HAS LITTLE IMPACT ON OVERALL ACCURACY. WHILE MACHINE LEARNING METHODS, LIKE RANDOM FOREST, EXPLORE INTERACTIONS BETWEEN PREDICTORS AND RACE OR ETHNICITY, SUICIDE ATTEMPT AND DEATH ARE RARE EVENTS, WHICH LIMITS THE INFORMATION AVAILABLE TO IDENTIFY RACE- AND ETHNICITY-SPECIFIC RISK FACTORS. THERE IS ALSO INSUFFICIENT GUIDANCE ON SAMPLE SIZE CALCULATIONS FOR PREDICTION STUDIES. WE WILL DEVELOP NOVEL STATISTICAL METHODS FOR RANDOM FOREST MODELS THAT REDUCE RACIAL AND ETHNIC DISPARITIES IN PERFORMANCE OF SUICIDE PREDICTION MODELS BY ADDRESSING GAPS IN CURRENT METHODS. AIM 1 WILL DEVELOP NEW PROCEDURES FOR PREDICTION MODEL ESTIMATION THAT MAXIMIZE PREDICTIVE PERFORMANCE WITHIN RACIAL AND ETHNIC SUBGROUPS, RATHER THAN MAXIMIZING AVERAGE PERFORMANCE ACROSS THE ENTIRE POPULATION. AIM 2 WILL INTEGRATE METHODS TO ADJUST FOR DIFFERENTIAL OUTCOME MISCLASSIFICATION IN PREDICTION MODEL ESTIMATION AND EVALUATION. AIM 3 WILL DESIGN SAMPLE SIZE CALCULATIONS TO DETERMINE IF A STUDY IS ABLE TO ACCURATELY PREDICT OUTCOMES WITHIN RACIAL AND ETHNIC SUBGROUPS. WE WILL USE EXISTING DATA ON SUICIDE RISK FACTORS AND OUTCOMES FOR 15 MILLION OUTPATIENT MENTAL HEALTH, 10 MILLION PRIMARY CARE, AND 2 MILLION EMERGENCY DEPARTMENT VISITS FROM THE NIMH- FUNDED MENTAL HEALTH RESEARCH NETWORK TO IMPLEMENT OUR METHODS AND ESTIMATE SUICIDE PREDICTION MODELS FOR EACH SETTING THAT ACCURATELY IDENTIFY PATIENTS AT HIGHEST RISK OF SUICIDE ACROSS ALL RACES AND ETHNICITIES.

HAWAII ASIAN AND PACIFIC ISLANDER DIABETES STUDY

UNDERSTANDING THE IMPACT OF EARLY LIFE FACTORS ON CARDIOMETABOLIC RISK THROUGHOUT THE LIFE COURSE IN A LARGE AND DIVERSE COHORT OF ADOLESCENTS AND YOUNG ADULTS - ABSTRACT CARDIOMETABOLIC CONDITIONS — SUCH AS HYPERTENSION, PREDIABETES, TYPE 2 DIABETES MELLITUS (T2D), DYSLIPIDEMIA, AND METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD) — ARE AMONG THE LEADING CAUSES OF MORBIDITY AND MORTALITY AMONG US ADULTS BUT ARE NOW SEVERELY AFFECTING YOUNGER GENERATIONS. CARDIOMETABOLIC CONDITIONS THAT EMERGE AMONG ADOLESCENTS AND YOUNG ADULTS (AYA) OFTEN HAVE A MORE AGGRESSIVE CLINICAL COURSE AND LEAD TO GREATER COMPLICATIONS THAN DO ADULT-ONSET ONES, MAKING IDENTIFICATION OF HIGH-RISK POPULATIONS AND TARGETED EARLY PREVENTION EFFORTS FOR AYA CRITICAL, PARTICULARLY GIVEN PERSISTENT RACIAL AND ETHNIC DISPARITIES ACROSS THE LIFE COURSE. ADOLESCENCE AND YOUNG ADULTHOOD ARE VULNERABLE DEVELOPMENTAL WINDOWS, IN WHICH EMERGING HEALTH RISKS MAY HAVE LIFELONG IMPLICATIONS FOR CARDIOVASCULAR DISEASES. HOWEVER, LITTLE IS KNOWN ABOUT THE EPIDEMIOLOGY OF CARDIOMETABOLIC OUTCOMES AMONG AYA POPULATIONS BECAUSE EXISTING STUDIES IN AYA ARE EXTREMELY LIMITED DUE TO A LACK OF POPULATION-BASED STUDIES WITH DIVERSE SAMPLES BEYOND BLACK AND LATINX POPULATIONS, SMALL SAMPLE SIZES, CROSS-SECTIONAL DESIGNS, AND LACK OF OBJECTIVE MEASURES OF CARDIOMETABOLIC OUTCOMES BEYOND BMI. IN ADDITION, THERE IS ALSO PRESSING INTEREST IN IDENTIFYING UPSTREAM RISK FACTORS, PARTICULARLY EARLY LIFE FACTORS, BECAUSE HUMAN METABOLIC AND ENDOCRINE SYSTEMS ARE PROGRAMMED EARLY IN LIFE. OUR LONG-TERM GOAL IS TO BETTER UNDERSTAND THE EPIDEMIOLOGY OF CARDIOMETABOLIC OUTCOMES AMONG AYA, IDENTIFYING HIGH-RISK GROUPS AND RISK FACTORS TO INFORM EARLY DETECTION AND DESIGN UPSTREAM INTERVENTION STRATEGIES TO MITIGATE HEALTH DISPARITIES. TO FILL EXTANT KNOWLEDGE GAPS AND INFORM FUTURE PREVENTION STRATEGIES, WE WILL CONDUCT A LARGE LONGITUDINAL COHORT STUDY BASED ON A DIVERSE POPULATION OF OVER 2.5 MILLION AYA MEMBERS (AGED 12 TO 26; 8% BLACK, 26% LATINX, 19% ASIAN, 1% NATIVE HAWAIIAN/PACIFIC ISLANDER, 0.5% NATIVE AMERICAN) AT KAISER PERMANENTE NORTHERN CALIFORNIA (KPNC), AN INTEGRATED HEALTH CARE SYSTEM WITH MEMBERSHIP REPRESENTATIVE OF THE SOURCE POPULATION. WE WILL USE ELECTRONIC HEALTH RECORD DATA TO LINK DIAGNOSIS, LABORATORY, AND OTHER SOCIODEMOGRAPHIC AND CLINICAL DATA TO DESCRIBE SEX- AND RACE/ETHNICITY-SPECIFIC INCIDENCE AND TEMPORAL TRENDS OF CARDIOMETABOLIC OUTCOMES AMONG AYA, BY SEX, AGE GROUP, RACE/ETHNICITY, AND BMI CATEGORIES (AIM 1). WE WILL ALSO INVESTIGATE HOW CHILDHOOD AND ADOLESCENT BMI TRAJECTORIES INFLUENCE CARDIOMETABOLIC OUTCOMES (AIM 2), KNOWLEDGE THAT IS LACKING AMONG AYA POPULATIONS. FINALLY, USING DATA FROM A SUB-COHORT THAT WAS BORN AT KPNC, WE WILL IDENTIFY PRENATAL AND EARLY FACTORS ASSOCIATED WITH THE CARDIOMETABOLIC RISKS IN AYA BY SEX AND RACE/ETHNICITY (AIM 3). RESULTS WILL INFORM EARLY TARGETED INTERVENTIONS AIMED AT LOWERING CARDIOMETABOLIC RISKS AMONG HIGH-RISK GROUPS, WITH THE POTENTIAL TO REDUCE HEALTH DISPARITIES THROUGHOUT THE LIFE COURSE. IN ADDITION, THE TIMING OF THE PROPOSED STUDY POSITIONS US ADVANTAGEOUSLY WITH A COMPREHENSIVE DATASET COVERING PRE-, DURING-, AND POST-PANDEMIC PERIODS. THIS UNIQUE TEMPORAL FRAMEWORK ALLOWS FOR AN EXAMINATION OF THE IMPACT OF THE PANDEMIC ON CARDIOMETABOLIC RISKS AMONG AYAS.

AI-ENABLED ECHOCARDIOGRAPHIC BIOMARKERS AND REAL-WORLD DATA FOR PREDICTING CANCER THERAPY-RELATED CARDIAC DYSFUNCTION - ABSTRACT: CANCER SURVIVORS HAVE UP TO A 42% HIGHER RISK OF CARDIAC DYSFUNCTION THAN NON-CANCER POPULATIONS, IN PART DUE TO SEQUELAE OF CARDIOTOXIC CANCER THERAPIES—COLLECTIVELY TERMED CANCER THERAPY–RELATED CARDIAC DYSFUNCTION (CTRCD). YET CURRENT SURVEILLANCE STRATEGIES SUFFER FROM LOW SENSITIVITY, POOR REPRODUCIBILITY, AND LACK OF PERSONALIZATION. THIS PROPOSAL AIMS TO TRANSFORM CARDIO-ONCOLOGY CARE BY INTEGRATING FDA-CLEARED ARTIFICIAL INTELLIGENCE (AI) ECHOCARDIOGRAPHIC BIOMARKERS WITH REAL-WORLD ELECTRONIC HEALTH RECORD (EHR) DATA TO IMPROVE EARLY DETECTION AND RISK STRATIFICATION OF CTRCD. LEVERAGING A DIVERSE COHORT OF OVER 34,000 PATIENTS TREATED WITH CARDIOTOXIC THERAPIES WITHIN AN INTEGRATED HEALTHCARE SYSTEM WITH COMPREHENSIVE DATA, WE WILL APPLY VALIDATED AI MODELS TO ARCHIVED ECHOCARDIOGRAMS TO IDENTIFY SUBCLINICAL CARDIAC DYSFUNCTION AND DEVELOP PREDICTIVE MODELS THAT GUIDE PERSONALIZED SURVEILLANCE. SPECIFIC AIMS INCLUDE: (1) EVALUATING AI-DERIVED BIOMARKERS FOR EARLY AND STANDARDIZED DETECTION OF CTRCD, AND (2) DEVELOPING AND VALIDATING MULTIMODAL PREDICTIVE MODELS COMBINING AI-ECHO AND EHR DATA. THIS WORK WILL GENERATE REGULATORY-GRADE EVIDENCE TO INFORM FDA GUIDANCE, IMPROVE CLINICAL OUTCOMES, AND ESTABLISH A SCALABLE FRAMEWORK FOR CARDIO-ONCOLOGY SURVEILLANCE IN REAL-WORLD SETTINGS.

ELECTRONIC CLINICAL SURVEILLANCE TO MEASURE AND IMPROVE SAFETY IN AMBULATORY CARE

UNDERSTANDING AND HONORING PATIENTS WITH MULTIPLE CHRONIC CONDITIONS

TEAM-BASED SAFE OPIOID PRESCRIBING

PATIENT REMINDERS AND NOTIFICATIONS

DISPARITIES IN CHRONIC ILLNESS CARE FOR PATIENTS WITH LANGUAGE BARRIERS

ARTIFICIAL INTELLIGENCE IMAGING BIOMARKERS OF LONGITUDINAL CARDIOVASCULAR STRESS - ABSTRACT ACROSS EVERY TYPE OF PREDICTION MODEL, APPLIED TO VIRTUALLY ANY POPULATION, THE SINGLE MOST SUBSTANTIAL CONTRIBUTOR TO INCIDENT CARDIOVASCULAR DISEASE (CVD) IS OLDER AGE. HOWEVER, OUR UNDERSTANDING OF WHY CARDIOVASCULAR RISK DRAMATICALLY RISES WITH ADVANCING AGE REMAINS LIMITED. EVIDENCE TO DATE SUGGESTS THAT CVD CULMINATES FROM AGE- RELATED CHANGES IN CARDIAC STRUCTURE AND FUNCTION THAT BEGIN VERY EARLY IN ADULTHOOD AND CONTINUE TO DEVELOP ON A BACKGROUND OF LIFELONG EXPOSURE TO RISK FACTORS – CONTRIBUTING TO AN ‘AGE GAP’ BETWEEN BIOLOGICAL AGE AND CHRONOLOGICAL AGE THAT GROWS OVER TIME. IT LOGICALLY FOLLOWS THAT A PERSON’S INCREASING BURDEN OF CARDIOVASCULAR RISK SHOULD MANIFEST AS PROGRESSIVE CARDIAC ABNORMALITIES THAT CAN BE TRACKED, ANALYZED, AND IDENTIFIED OVER THE LIFESPAN. UNTIL RECENTLY, METHODS FOR ASSESSING THE CARDIOVASCULAR ‘AGE GAP’ HAVE BEEN LIMITED. RECENT ADVANCES IN ARTIFICIAL INTELLIGENCE (AI), WHEN APPLIED TO BIOMEDICAL IMAGES, INDICATE THAT DEEP LEARNING ALGORITHMS CAN BOTH OFFER PRECISE MEASUREMENTS BEYOND HUMAN FIDELITY AND ALSO IDENTIFY SUBTLE TRAITS IN IMAGING THAT ARE UNRECOGNIZED BY THE HUMAN EYE. IN FACT, OUR PRIOR WORK APPLYING AI TO ECHOCARDIOGRAPHY AS WELL AS OTHERS APPLYING AI TO OTHER FORMS OF MEDICAL IMAGING, HAVE SHOWN DEEP LEARNING CAN NOT ONLY REPRODUCE STANDARD MEASURES OF CARDIAC STRUCTURAL AND FUNCTION BUT IS ALSO IDENTIFY CVD RISK FEATURES INCLUDING CHRONOLOGIC AGE, BIOLOGICAL SEX, DIABETES, HYPERTENSION, AND SMOKING. IN EFFECT, AI APPLIED TO ECHOCARDIOGRAPHY NOW OFFERS THE POTENTIAL TO CAPTURE AN AGGREGATE MEASURE OF CARDIAC AGING AND, IN TURN, IDENTIFY INTERVENABLE TARGET FOR MITIGATING AGE-RELATED CVD RISK. THUS, WE HYPOTHESIZE THAT AI METHODS APPLIED TO ECHOCARDIOGRAPHY CAN BE USED TO NOT ONLY PREDICT BIOLOGICAL CARDIOVASCULAR AGE BUT ALSO (I) IDENTIFY TRAJECTORIES OF ACCELERATED VERSUS DELAYED CARDIOVASCULAR AGING, (II) DISCERN KEY CONTRIBUTORS TO ACCELERATED CARDIOVASCULAR AGING PHENOTYPES, AND (III) ELUCIDATE THE EXCESS AGE- RELATED RISK FOR SPECIFIC CVD OUTCOMES THAT MAY BE INDEPENDENT FROM ANY CO-EXISTING BURDEN OF RISK FACTORS OR SUBCLINICAL CARDIAC DISEASE. TO TEST THESE HYPOTHESES, WE WILL LEVERAGE ECHOCARDIOGRAPHY IMAGES THAT ARE ACQUIRED AS A PART OF ROUTINE CLINICAL CARE IN ADDITION TO SERIAL IMAGING FREQUENTLY OBTAINED IN LARGE COHORT STUDIES OF AGING ADULTS. BECAUSE HEALTHCARE COHORTS ARE ENRICHED FOR PATIENTS WITH ACCELERATED AGING TRAJECTORIES, WHILE EPIDEMIOLOGIC COHORTS ARE ENRICHED FOR INDIVIDUALS WITH DELAYED AGING TRAJECTORIES, WE PLAN TO ANALYZE IMAGING AND OUTCOMES DATA COLLECTED FROM BOTH TYPES OF COHORTS. ACCORDINGLY, OUR AIMS ARE TO TRAIN AND VALIDATE AI MODELS ON PREDICTING BIOLOGICAL AGE FROM CARDIAC IMAGING AND IDENTIFY ITS COMPONENT CONTRIBUTORS TO EXCESS CARDIOVASCULAR RISK IN BOTH THE HEALTHCARE SETTING AND IN THE COMMUNITY SETTING.

POPULATION-BASED INCIDENCE, TIME TRENDS, AND EARLY LIFE FACTORS ASSOCIATED WITH TYPE 2 DIABETES AMONG ASIAN AMERICAN, NATIVE HAWAIIAN, AND PACIFIC ISLANDER ADOLESCENTS AND YOUNG ADULTS - THE NUMBER OF ADOLESCENTS AND YOUNG ADULTS (AYA) WITH TYPE 2 DIABETES (T2D) HAS RISEN SHARPLY IN PARALLEL WITH THE OBESITY EPIDEMIC IN THE U.S. IF CURRENT TRENDS CONTINUE, THE NUMBER OF T2D CASES AMONG AMERICAN YOUTH IS PROJECTED TO INCREASE MORE THAN SEVEN-FOLD BY 2060. YOUTH-ONSET T2D IS DEBILITATING, TYPICALLY WITH A MORE AGGRESSIVE CLINICAL PRESENTATION COMPARED WITH ADULT-ONSET T2D. AYA OF ASIAN AMERICAN (ASA) AND PACIFIC ISLANDER (PI) DESCENT ARE EXPERIENCING THE STEEPEST YEARLY INCREASE IN T2D INCIDENCE. UNFORTUNATELY, CURRENT EPIDEMIOLOGIC AND ETIOLOGIC STUDIES OF AYA T2D ARE EXTREMELY LIMITED DUE TO A LACK OF POPULATION-BASED STUDIES WITH SUFFICIENTLY LARGE SAMPLES, AND ALMOST NO DATA ON T2D IN ASA AND PI YOUTH. DESPITE THEIR RAPIDLY GROWING POPULATION, LITTLE IS KNOWN ABOUT THE RISK FACTORS AMONG ASA AND PI INDIVIDUALS BECAUSE THEY HAVE NOT BEEN WELL STUDIED; WHEN THEY ARE INCLUDED IN RESEARCH, THESE SUBPOPULATIONS ARE VERY OFTEN AGGREGATED INTO A SINGLE GROUP, MASKING IMPORTANT HEALTH DIFFERENCES. OUR LONG-TERM GOAL IS TO BETTER UNDERSTAND THE EPIDEMIOLOGY OF T2D AMONG AYA, WITH A SPECIAL FOCUS ON ASA AND PI, IDENTIFYING HIGH-RISK SUBPOPULATIONS AND MODIFIABLE RISK FACTORS TO INFORM EARLY DETECTION AND DESIGN UPSTREAM INTERVENTION STRATEGIES TO IMPROVE THE HEALTH OF ALL AYA. TO FILL EXTANT KNOWLEDGE GAPS AND INFORM FUTURE GUIDELINES AND PREVENTION STRATEGIES, WE WILL CONDUCT A LARGE LONGITUDINAL COHORT STUDY OF OVER 5 MILLION AYA MEMBERS AT KAISER PERMANENTE NORTHERN CALIFORNIA AND KAISER PERMANENTE SOUTHERN CALIFORNIA, INTEGRATED HEALTHCARE ORGANIZATIONS WITH MEMBERSHIPS REPRESENTATIVE OF THE SOURCE POPULATION. ALL MEMBERS AGES 10 TO 30 IDENTIFIED FROM 2007 TO THE PRESENT WILL BE INCLUDED. WE WILL USE ELECTRONIC HEALTH RECORD DATA TO LINK DIAGNOSIS, LABORATORY, AND OTHER DEMOGRAPHIC AND CLINICAL DATA TO DESCRIBE INCIDENCE AND TEMPORAL TRENDS OF YOUTH-ONSET T2D AMONG ASA AND PI AYA (AIM 1). WE WILL THEN INVESTIGATE EARLY LIFE (E.G., GESTATIONAL DIABETES) AND CHILDHOOD RISK FACTORS ASSOCIATED WITH YOUTH-ONSET T2D, AND EXAMINE DIFFERENCES ACROSS RELEVANT SUBGROUPS (AIM 2). THIS STUDY WILL ADVANCE OUR UNDERSTANDING OF THE EPIDEMIOLOGY AND ETIOLOGY OF YOUTH-ONSET T2D IN ASA AND PI SUBPOPULATIONS AND PROVIDE EVIDENCE NEEDED TO INFORM FUTURE PREVENTION TOOLS TO IMPROVE THE HEALTH OF AMERICAN AYA.

THE LEARNING AND EDUCATIONAL ATTAINMENT OF PRETERM AND AT-RISK INFANTS - PROJECT SUMMARY/ABSTRACT INFANTS BORN PREMATURELY (<37 WEEKS’ GESTATION) OR AT TERM WITH CONGENITAL ANOMALIES OR PERINATAL CONDITIONS ARE AT INCREASED RISK OF MORTALITY, NEURODEVELOPMENTAL MORBIDITY, AND DIFFICULTY WITH ACADEMIC ACHIEVEMENT. SPECIFICALLY, CHILDREN BORN PRETERM SHOW DEFICITS IN MATHEMATICS, LANGUAGE DECODING, AND READING COMPREHENSION SUBSKILLS COMPARED TO TERM CHILDREN. ACADEMIC PERFORMANCE IS A USEFUL SUMMARY MARKER FOR FUNCTIONAL LIMITATIONS CAUSED BY NEURODEVELOPMENTAL IMPAIRMENT AND IS AN INTERMEDIATE OUTCOME FOR LIFELONG HEALTH. MOST OF OUR KNOWLEDGE ABOUT THE INTERSECTION OF HEALTH AND EDUCATION IS DERIVED FROM STUDIES THAT RELY ON PARENT RECOLLECTION. DETAILED LONGITUDINAL HEALTH INFORMATION TIED TO EDUCATIONAL OUTCOMES IS LACKING. MOREOVER, OUR KNOWLEDGE ABOUT THE IMPACT OF PARTICIPATION IN PROGRAMS LIKE HIGH RISK INFANT FOLLOW UP (HRIF) AND EARLY INTERVENTION (EI) ON DOWNSTREAM ACADEMIC ACHIEVEMENT IS LIMITED. WE PROPOSE A 5-YEAR STUDY TO EXAMINE WHETHER UNIVERSAL EARLY IDENTIFICATION OF NEURODEVELOPMENTAL DISABILITY AND EQUITABLE AND TIMELY REFERRAL TO AND RECEIPT OF APPROPRIATE SUPPORT SERVICES CAN MITIGATE DEVELOPMENTAL DEFICITS AND IMPROVE ACADEMIC OUTCOMES. WE WILL LEVERAGE THE UNIQUE PARTNERSHIP IN LOS ANGELES BETWEEN KAISER PERMANENTE SOUTHERN CALIFORNIA (KPSC), ONE OF THE LARGEST INTEGRATED HEALTH SYSTEMS, AND LOS ANGELES UNIFIED SCHOOL DISTRICT (LAUSD), THE SECOND LARGEST SCHOOL DISTRICT IN THE US. ACADEMIC OUTCOMES WILL BE MEASURED USING (1) STANDARDIZED TEST SCORES USING THE CALIFORNIA ASSESSMENT OF STUDENT PERFORMANCE AND PROGRESS (SMARTER BALANCE SUMMATIVE ASSESSMENTS, ENGLISH LANGUAGE ARTS AND MATHEMATICS COMPONENTS), (2) ATTENDANCE, (3) COURSE GRADES AND GRADE POINT AVERAGE, AND (4) GRADUATION. WE PROPOSE TO A) MERGE ELECTRONIC HEALTH AND BILLING DATA FROM KPSC AND ACADEMIC MEASURES FROM LAUSD. USING THIS NOVEL DATA RESOURCE; WE WILL B) USE TREE-BASED CLASSIFICATION AND MULTI-LEVEL GROWTH MIXTURE MODELLING TO COMPARE ACADEMIC TRAJECTORIES BETWEEN AT-RISK PRETERM AND TERM INFANTS AND LOW-RISK TERM COUNTERPARTS; C) IDENTIFY PREDICTORS OF REFERRAL AND PARTICIPATION IN HRIF AND EI AND EXAMINE MEDIATORS AND MODERATORS OF THE ASSOCIATION BETWEEN PERINATAL RISK AND PARTICIPATION IN HRIF AND EI USING LOGISTIC AND MIXED EFFECTS NEGATIVE BINOMIAL REGRESSION, MEDIATION, MODERATION ANALYSES; AND D) EXAMINE THE ASSOCIATION BETWEEN PARTICIPATION IN HRIF AND EI AND ACADEMIC OUTCOMES WITH A MATCHED PROPENSITY SCORE ANALYSIS AND SUBSEQUENT MIXED EFFECTS REGRESSION MODELS. THE PROPOSED STUDY ALIGNS WITH THE MISSION OF THE NIH NICHD TO ENSURE THAT ALL CHILDREN HAVE THE CHANCE TO ACHIEVE THEIR FULL POTENTIAL FOR PRODUCTIVE LIVES. THE ASSOCIATION OF SERVICE USE (EI/HRIF) AND EDUCATIONAL OUTCOMES IDENTIFIED IN THIS STUDY WILL INFORM POLICY AND QUALITY EFFORTS TO IMPROVE CONNECTIONS BETWEEN DEVELOPMENTAL SERVICES, HEALTH SYSTEMS, AND SCHOOL DISTRICTS.

PRENATAL EXPOSURE TO ORGANOPHOSPHATE ESTER FLAME RETARDANTS AND PLASTICIZERS (OPES), GENE-ENVIRONMENT INTERACTION, AND CHILD NEURODEVELOPMENT - ABSTRACT THE PREVALENCE OF AUTISM AND ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD) IS INCREASING, YET THEIR ETIOLOGY IS POORLY UNDERSTOOD. A COMPLEX COMBINATION OF ENVIRONMENTAL AND GENETIC FACTORS APPEARS TO CONTRIBUTE TO BOTH CONDITIONS BUT MOST STUDIES TO DATE HAVE EXAMINED THESE FACTORS IN ISOLATION. THE INCOMPLETE STUDY OF GENE- ENVIRONMENT (GXE) INTERACTIONS IN AUTISM AND ADHD REMAINS A SIGNIFICANT BARRIER TO PROGRESS IN UNDERSTANDING THEIR ETIOLOGY. MANY ENDOCRINE-DISRUPTING CHEMICALS (EDCS) APPEAR TO BE NEUROTOXIC AND THEIR ROLE IN THE DEVELOPMENT OF AUTISM AND ADHD MERITS CLOSER SCRUTINY. ORGANOPHOSPHATE ESTER FLAME RETARDANTS AND PLASTICIZERS (OPES) ARE EDCS OF EMERGING CONCERN, WITH HUMAN EXPOSURES INCREASING RAPIDLY WHEN THEY REPLACED POLYBROMINATED DIPHENYL ETHERS (PBDE) FLAME RETARDANTS STARTING IN THE EARLY 2000S. MOUNTING HUMAN EVIDENCE SUGGESTS THAT OPE EXPOSURE DURING PREGNANCY IS DETRIMENTAL TO CHILD NEURODEVELOPMENT. STUDIES SPECIFICALLY LINKING PRENATAL OPE EXPOSURE TO AUTISM AND ADHD RELATED OUTCOMES ARE CONCERNING; THESE ASSOCIATIONS WARRANT CLOSER EXAMINATION. NOTABLY, EARLIER STUDIES OF OPES AND NEURODEVELOPMENT DID NOT CONSIDER GENETIC SUSCEPTIBILITY, A CONCERNING KNOWLEDGE GAP THAT POTENTIALLY OBSCURES SUBGROUPS MORE SENSITIVE TO OPES. GENETICS MAY MODIFY SENSITIVITY TO CHEMICALS BY SHAPING THE EFFICIENCY OF A PERSON’S METABOLISM OF XENOBIOTICS OR MAKING CERTAIN PHYSIOLOGIC PATHWAYS MORE SUSCEPTIBLE TO EXOGENOUS DISRUPTION. THE PROPOSED STUDY SEEKS TO BUILD ON THIS PREVIOUS LITERATURE AND FURTHER EXPLORE FACTORS THAT MODULATE SENSITIVITY TO PRENATAL OPE EXPOSURE IN THE CONTEXT OF CHILD NEURODEVELOPMENT. SPECIFICALLY, WE PROPOSE A NOVEL INVESTIGATION OF THE GENETIC UNDERPINNINGS OF THE ASSOCIATION OF PRENATAL OPE EXPOSURE AND CHILD AUTISM AND ADHD USING THE RICH AND COMPLEMENTARY DATA RESOURCES OF TWO COHORTS: 1) THE DIVERSE PARTICIPANT POPULATION OF THE NIH ENVIRONMENTAL INFLUENCES ON CHILD HEALTH OUTCOMES (ECHO) COHORT, WHICH HAS A LARGE SAMPLE SIZE AND OPES MEASURED AT ONE TIME POINT DURING PREGNANCY AND 2) THE KAISER PERMANENTE PETALS COHORT, A SMALLER, DIVERSE COHORT WITH OPES MEASURED AT TWO PREGNANCY TIME POINTS. OUR OVERARCHING HYPOTHESIS IS THAT GENETIC VARIATION ACROSS THE GENOME, POTENTIALLY IN GENES CRITICAL TO NEURODEVELOPMENT AND XENOBIOTIC METABOLISM, MAY MAKE SOME INDIVIDUALS MORE SUSCEPTIBLE TO OPE NEUROTOXICITY DURING THE PRENATAL PERIOD. IN AIM 1 WE WILL PERFORM A NOVEL GENOME-WIDE BY ENVIRONMENT INTERACTION STUDY (GWEIS) OF MATERNAL AND CHILD GENETICS AND LEVELS OF URINARY OPE EXPOSURE DURING PREGNANCY IN RELATION TO CHILD NEURODEVELOPMENT; AIM 2 WILL HARNESS POLYGENIC SCORES (PGS) FOR AUTISM AND ADHD TO EXAMINE MODIFICATION OF THE OPE AND CHILD OUTCOMES RELATIONSHIP. IN AIM 3, WE WILL REPLICATE AND EXPAND ON FINDINGS FROM ECHO IN THE PETALS COHORT. THE PROPOSED WORK WILL LAY THE GROUNDWORK FOR CONTINUED STUDY OF GXE WITH RESPECT TO OPES WHICH COULD BE USED TO INFORM POLICIES TO PROTECT SUSCEPTIBLE SUBGROUPS AND IDENTIFY MODIFIABLE ENVIRONMENTAL RISK FACTORS TO LESSEN THE DISABILITY ASSOCIATED WITH CHILD AUTISM, ADHD, AND OTHER NEURODEVELOPMENTAL CONDITIONS.

FACILITATING LOWER OPIOID AMOUNTS THROUGH TAPERING

ADVANCING IMPLEMENTATION SCIENCE THROUGH MEASURE DEVELOPMENT AND EVALUATION

MISSED HOME HEALTH CARE IN OLDER ADULTS WITH DEMENTIA: IDENTIFYING DRIVERS, OUTCOMES, AND COSTS - PROJECT SUMMARY/ABSTRACT THE OVERARCHING GOAL OF THIS R01 PROPOSAL “MISSED HOME HEALTH CARE IN OLDER ADULTS WITH DEMENTIA: IDENTIFYING DRIVERS, OUTCOMES, AND COSTS” IS TO IDENTIFY KEY DRIVERS AND MITIGATORS OF MISSED HOME HEALTH CARE (HHC), TEST WHETHER MISSED HHC IS RELATED TO CLINICAL OUTCOMES AND COSTS, AND IDENTIFY BEST PRACTICES TO REDUCE MISSED HHC FOR VULNERABLE OLDER ADULTS WITH ALZHEIMER’S DISEASE AND RELATED DEMENTIAS (ADRD). HOME HEALTH CARE PROVIDES KEY IN-HOME SUPPORTS, INCLUDING NURSING AND THERAPIES, FOR OLDER ADULTS WITH ADRD AND THEIR CAREGIVERS FOLLOWING HOSPITALIZATION. HOWEVER, APPROXIMATELY ONE-THIRD OF PATIENTS NEVER RECEIVE HHC THAT IS PLANNED FOLLOWING HOSPITALIZATION, AND RATES OF MISSED HHC MAY BE EVEN HIGHER IN ADULTS WITH DEMENTIA. MISSED HHC MAY BE RELATED TO A SHRINKING NUMBER OF HHC AGENCIES, LIMITED HHC ACCESS IN DISADVANTAGED OR RURAL COMMUNITIES, PATIENTS DECLINING HHC SERVICES, AND/OR PAYER-RELATED FACTORS SUCH AS PRIOR AUTHORIZATIONS. MISSED HHC IS ASSOCIATED WITH ADVERSE OUTCOMES INCLUDING HIGHER HOSPITAL READMISSIONS, MORTALITY, AND COSTS, YET OUTCOMES FOR OLDER ADULTS WITH ADRD WHO HAVE MISSED HHC AFTER HOSPITAL DISCHARGE ARE UNKNOWN. WE PROPOSE USING A MIXED METHODS APPROACH TO: (1) IDENTIFY CORRELATES OF MISSED HOME HEALTH CARE FOLLOWING HOSPITAL DISCHARGE IN OLDER ADULTS WITH DEMENTIA (QUANTITATIVE);(2) CHARACTERIZE DRIVERS AND MITIGATORS OF MISSED HOME HEALTH CARE FROM THE PERSPECTIVES OF HOSPITALISTS, DISCHARGE PLANNERS, HOME HEALTH CARE CLINICIANS, CAREGIVERS AND OLDER ADULTS WITH ADRD (QUALITATIVE); AND (3) TEST IF MISSED HHC IS ASSOCIATED WITH HIGHER READMISSIONS, MORTALITY, AND/OR HEALTHCARE COSTS AFTER DISCHARGE FOR OLDER ADULTS WITH ADRD (QUANTITATIVE). OUR INVESTIGATOR TEAM HAS EXPERTISE WITH QUALITATIVE, QUANTITATIVE, AND MIXED METHODS IN THE HHC SETTING AND INCLUDES EXPERTS IN GERIATRICS, ADRD, AND HEALTH ECONOMICS USING MEDICARE AND MEDICARE ADVANTAGE DATA. OUR WORK IS GUIDED BY BOTH THE CONCEPTUAL FRAMEWORK TO GUIDE INTERVENTION RESEARCH ACROSS THE TRAJECTORY OF DEMENTIA CAREGIVING AND THE PRACTICAL, ROBUST IMPLEMENTATION AND SUSTAINABILITY MODEL (PRISM) FRAMEWORK. THIS INNOVATIVE WORK WILL ADVANCE UNDERSTANDING OF MISSED HHC FOR PATIENTS WITH ADRD, WHICH WILL BE CRITICAL AS POST-ACUTE CARE CONTINUES TO SHIFT FROM FACILITIES TO THE HOME, MEDICARE ADVANTAGE ENROLLMENT CONTINUES TO GROW, AND THE NUMBER OF ADULTS WITH ADRD CONTINUES TO SURGE. THIS PROPOSAL IS RESPONSIVE TO HIGH-PRIORITY TOPIC AREAS DESCRIBED IN NOT-AG-21-046, INCLUDING CARE TRANSITIONS FROM HOSPITAL TO HOME SETTINGS WITH ATTENTION TO TIMELINESS AND AVAILABILITY OF HHC TO SUPPORT CAREGIVERS FOR OLDER ADULTS WITH ADRD. ULTIMATELY, WE AIM TO LEVERAGE KEY FINDINGS TO DEVELOP INTERVENTIONS AND POLICY RECOMMENDATIONS THAT WILL REDUCE MISSED HHC AND IMPROVE CLINICAL OUTCOMES FOR OLDER ADULTS WITH ADRD AND THEIR CAREGIVERS.

HEALTH CARE IMPROVEMENT FOR AGING WOMEN

ANTIDEPRESSANT TREATMENT AND RISK OF OBESITY

LONG-TERM OPIOID MANAGEMENT OF CHRONIC PAIN: TRENDS AND RISKS

MULTI-CENTER STUDY OF PANCREATIC CANCER ETIOLOGY

PREDICTIONS OF RESPONSE TO TREATMENT IN FUNGAL KERATITIS

THE ROLE OF ADIPOKINES IN GLUCOSE REGULATION AND METABOLIC DECLINE

A CASE-CONTROL STUDY TO EVALUATE BROAD-SPECTRUM ANTIBIOTIC USE AND HIGH BIRTH WEIGHT AS POTENTIAL RISK FACTORS FOR EARLY-ONSET COLORECTAL CANCER - PROJECT ABSTRACT THE INCIDENCE OF COLORECTAL CANCER IN YOUNG ADULTS UNDER AGE 50 (REFERRED TO AS EARLY ONSET COLORECTAL CANCER [EOCRC]) HAS BEEN RISING BY A STRIKING 2% PER YEAR IN THE UNITED STATES SINCE THE 1990S. EVEN MORE NOTABLY, A SIGNIFICANT INCREASE IN EOCRC IS EXPERIENCED BY EVERY 5-YEAR AGE GROUP FROM AS YOUNG AS AGE 20 YEARS. THE ACCOMPANYING HUMAN TOLL SHOULD NOT BE UNDERSTATED CONSIDERING THE MIRRORING RISE OF DEATHS DUE TO EOCRC, AND THE LOSS IN QUALITY OF LIFE GIVEN THAT MOST EOCRC ARE DIAGNOSED AT ADVANCED STAGES. DESPITE URGENT NEEDS TO INTERRUPT THIS TRAJECTORY, FACTORS RESPONSIBLE FOR THE RISE OF EOCRC ARE UNKNOWN, RENDERING THE DEVELOPMENT OF EFFECTIVE CANCER CONTROL STRATEGIES DIFFICULT. THIS STUDY SEEKS TO SHED LIGHT ON EOCRC RISK FACTORS THAT MAY CONTRIBUTE TO THE RISING INCIDENCE OF THIS DISEASE, DIRECTLY ADDRESSING PROVOCATIVE QUESTION1 FROM RFA-CA-20- 004: “WHAT ARE THE UNDERLYING CAUSES OF THE UNEXPLAINED RISING INCIDENCE IN EARLY-ONSET CANCERS?” EVIDENCE SUGGESTS THAT EOCRC MAY BE A DISTINCT DISEASE SUBSET WITH DIFFERENTIAL KEY RISK FACTORS FROM LATE-ONSET CRC. TO DATE, STUDIES THAT INVESTIGATED EOCRC ETIOLOGY REMAIN SPARSE, AND THEY MOSTLY FOCUSED ON THE ROLE OF ESTABLISHED RISK FACTORS FOR LATE-ONSET CRC, SUCH AS OBESITY, DIET AND PHYSICAL ACTIVITIES. THERE HAS BEEN A GENERAL LACK OF STUDIES THAT EVALUATE THE ROLE OF ALTERNATIVE RISK FACTORS SUCH AS THOSE THAT INVOLVE GUT DYSBIOSIS AND EARLY LIFE EXPOSURES IN EOCRC ETIOLOGY. TO FILL THIS CRITICAL GAP, WE WILL TEST NOVEL HYPOTHESES ON THE ROLES OF BROAD-SPECTRUM ANTIBIOTIC USE AND HIGH BIRTH WEIGHT IN EOCRC ETIOLOGY. USE OF BROAD-SPECTRUM ANTIBIOTICS RESULTS IN INTENSE AND LONG-LASTING GUT DYSBIOSIS, WHICH IS STRONGLY IMPLICATED IN CRC CARCINOGENESIS. FURTHER, ANIMAL STUDIES AND RECENT EPIDEMIOLOGIC EVIDENCE SUPPORTS THE ROLE OF BROAD-SPECTRUM ANTIBIOTICS AS CRC CARCINOGENS. HIGH BIRTH WEIGHT, LIKELY REFLECTING ALTERED IN-UTERO PROGRAMMING OF KEY HORMONE PATHWAYS SUCH AS THE INSULIN-LIKE GROWTH FACTOR SYSTEM AND HIGHER NUMBER OF STEM CELLS AT RISK FOR CARCINOGENESIS, HAS BEEN LINKED TO RISK OF OTHER YOUNG-ONSET CANCERS AND LATE-ONSET CRC. FURTHER, BOTH BROAD-SPECTRUM ANTIBIOTIC USE AND HIGH BIRTH WEIGHT HAVE BEEN ON THE RISE FOR DECADES PRECEDING THE RISE OF EOCRC. WE WILL USE A POPULATION-BASED, NESTED CASE-CONTROL STUDY DESIGN, INCLUDING ~1,100 EOCRC CASES DIAGNOSED BETWEEN 2009- 2021 AT KAISER PERMANENTE SOUTHERN CALIFORNIA (KPSC) TO CARRY OUT THE FOLLOWING SPECIFIC AIMS: (SA1) TEST THE HYPOTHESIS THAT GREATER EXPOSURE TO BROAD-SPECTRUM ANTIBIOTICS INCREASES RISK OF EOCRC; AND (SA2) TEST THE HYPOTHESIS THAT HIGH BIRTH WEIGHT INCREASES RISK OF EOCRC. KPSC'S UNIQUE STRENGTHS INCLUDE LARGE SAMPLE SIZE, COMPREHENSIVE ELECTRONIC MEDICAL RECORDS, LONG-TERM MEMBERSHIP RETENTION, AND GREAT RACIAL/ETHNIC DIVERSITY. AT THE COMPLETION OF THESE AIMS, WE EXPECT TO (1) OFFER NEW INSIGHTS INTO THE CARCINOGENESIS OF EOCRC; (2) FACILITATE THE DEVELOPMENT OF EOCRC RISK PREDICTION MODELS; (3) INFORM TARGETED EARLY SCREENING STRATEGIES; AND (3) INFORM NOVEL PREVENTION STRATEGIES TO AMEND THIS DEVASTATING EPIDEMIC.

DAT- IMPLEMENTING ROUTINE SCREENING FOR CANNABIS AND OTHER DRUG USE DISORDERS IN PRIMARY CARE: IMPACT ON DIAGNOSIS AND TREATMENT IN A RANDOMIZED PRAGMATIC TRIAL IN 22 CLINICS