Black, Latinx, and Indigenous populations in the US face a disproportionate burden of poor health outcomes. Progress toward eliminating gaps in health outcomes is minimal, despite increasing investments in and awareness of health inequities. Recognizing that those inequities are rooted in the conditions in which we live, grow, work, and learn, there has been increased attention toward social determinants of health. In the past several years, health systems and the federal government, through Medicare and Medicaid, have committed billions of dollars to address health-related social needs such as housing, nutrition, and transportation. Though increasingly recognized as the root cause of unequal mortality and disease burden, structural racism is infrequently considered, poorly understood, and inadequately measured. Using a structural racism framework, this study will create a neighborhood-level structural racism effect index by compositing publicly available data. Including data about housing, transportation, education, wealth and poverty, social cohesion, the built environment, employment, and criminal justice, the structural racism effect index will capture broad and interwoven effects of past and current racist policies. The index will assign a score of 0-100 to each census tract in the US and will be tested against publicly available outcome data such as average area life expectancy and prevalence of select health outcomes. The novel structural racism effect index may be used to predict costs and outcomes, direct resources, and inform decision-making about under-resourced populations. To illustrate the policy implications of a measure for the effects of structural racism, the index will be used to characterize the Medicaid population as a means of providing insight into where investments should be made. Using Massachusetts as a test case, this project will quantify the extent to which structural racism's effects modify the impact of a $149 million program to address the health-related social needs of the Massachusetts Medicaid population. 1

Cardiovascular trajectories begin in early childhood and continue across the life course. Early recognition and management of cardiovascular disease (CVD) risk factors in childhood stand to improve these trajectories and prevent CVD risk factors in adulthood. One CVD risk factor which in conjunction with obesity has gained prominence in childhood and which affects about 1 in every 25 children in the U.S is hypertension. Health disparities which are intrinsically linked to social determinants of health (i.e., the circumstances that children live in), persist in the prevalence of hypertension with consistently higher rates of this condition seen in those of lower socioeconomic status and those of Black race and Latino ethnicity. The American Academy of Pediatrics (AAP) 2017 Clinical Practice Guidelines recommend regular screening and follow-up for the detection and management of hypertension. However, diagnosis of this condition is rare (~74% undiagnosed), and there are racial disparities in the likelihood of diagnosis as white children are more likely to have this condition diagnosed. Understanding the processes that lead to a diagnosis of hypertension (e.g., blood pressure screening and follow-up), since the release of the updated AAP guidelines, is lacking. Therefore, the goal of the present investigation is to describe the current state of pediatric blood pressure screening and follow-up according to the 2017 AAP guidelines. Using retrospective electronic health record data for children aged 3-17 years from the UMass Memorial Health Care System, a safety-net system, and the largest non-for profit health care system in Central Massachusetts, we will: (1) conduct a one year period prevalence study to quantify the prevalence of guideline adherent blood pressure screening and examine disparities in lack of receipt of guideline concordant care; (2) conduct a cohort study through which we will describe the cumulative incidence of guideline adherent follow-up after the detection of high blood pressure and disparities in the lack of receipt of guideline concordant care; and (3) conduct a qualitative study through which we will describe providers’ experiences with and perceptions of clinical practice guidelines for pediatric blood pressure screening and follow-up. Through the present work it is hypothesized that inequities in care, heterogeneity in follow-up, and challenges to guideline adherence will be identified to inform future efforts to improve clinical practice guideline uptake and pediatric preventive care. Supported by a robust academic environment at the University of Massachusetts Medical School, and a rigorous, tailored training plan, this F31 will position Ms. Goulding to become an independent investigator addressing CVD health disparities among youth.

The current U.S. opioid epidemic has fueled an increase in injection drug use and, in turn, an alarming surge in new hepatitis C virus (HCV) infections. Between 2010 and 2015, the incidence of HCV increased by 294% nationally, driven primarily by a rise in injection drug use and risky injection behavior – namely syringe sharing. This growing epidemic has disproportionately affected young people who inject drugs (PWID) in rural communities. There is an urgent need to implement tailored and effective harm reduction strategies to rural PWID who are disproportionately impacted by HCV. Although research has shown that syringe services and pharmacy syringe sales (i.e sterile syringe sources) are associated with a reduction in injection-mediated risks and HIV transmission, the evidence for whether these services reduce HCV risk among PWID remains mixed. This proposal will applying the risk environment model to evaluate the influence of sterile syringe sources on the HCV risk environment. Specifically, this proposal will evaluate whether spatial proximity to sterile syringe sources and receptive secondary syringe exchange are associated with HCV serostatus among rural PWID. The aims are: (1) To evaluate the association between road network distance to the nearest sterile syringe source (SSP or pharmacy that sells nonprescription syringes) and HCV serostatus; (2) To use egocentric social network analysis to evaluate the association between receptive secondary syringe exchange and HCV serostatus; (3) to explore and unpack rural PWIDs’ perceptions of and experiences with syringe acquisition and syringe sharing practices through in-depth interviews. These findings could help inform the development of future harm reduction interventions in rural New England, a region of the country that has been particularly hard hit by the opioid epidemic and related HCV infections.

A glaring sexual orientation-related disparity is in the prevalence of disordered eating behaviors (DEBs), including severe calorie restriction, self-induced vomiting, laxative and diet pill use, and binge-eating. One in three sexual minority young people (lesbian, gay, bisexual, and other non-heterosexual individuals) engage in DEBs, a seven-fold higher odds than their heterosexual peers. There are considerable health consequences associated with these behaviors, such as metabolic and reproductive health issues, substance use, depression, and suicidality. However, research on DEBs lags behind that on other sexual orientation-related health disparities, with critical gaps including failing to consider both within-group diversity in risk and the upstream social determinants of the observed disparities. Importantly, experiencing multiple forms of social disadvantage has been shown to increase risk of eating-related pathologies, including DEBs. Gender nonconforming and higher-weight (i.e., overweight/obese) statuses are especially relevant dimensions of disadvantage to consider, as these groups experience high levels of appearance-based discrimination and may use DEBs as dangerous body-modification practices to cope. Sexual minorities who experience further marginalization through membership in these groups may encounter unique and/or compounding social stressors that exacerbate risk. Examining the intersectionality of sexual orientation, gender expression, and weight status is thus critical to addressing these research gaps. Using the Growing Up Today Study (GUTS), a national longitudinal cohort study of over 27,000 participants (~20% of whom are sexual minorities), the aims of this proposal are to: 1) Quantify the intersectional effects of sexual orientation, gender expression, and weight status on risk of DEBs among young adults; 2) Quantify the effects of interpersonal-level determinants (bullying victimization, weight-based harassment) on risk of DEBs by sexual orientation, and evaluate differences by gender expression and/or weight-status; and 3) Quantify the effects of structural-level determinants (discriminatory social conditions, state policies) on risk of DEBs by sexual orientation, and evaluate differences by gender expression and/or weight-status. The National Academy of Medicine’s 2011 landmark report on sexual minority health stressed the importance of adopting an intersectional framework for disparities research to inform the development of inclusive health equity efforts. Applying this lens through leveraging novel statistical methods will further understanding of a critically understudied sexual minority health issue and help identify high-risk subgroups and modifiable contextual risk factors. A tailored training plan accompanies this proposal and outlines the steps required to advance the Applicant’s career as an independent researcher focused on intersectional health disparities research.

Atrial fibrillation (AF) is a cardiac rhythm abnormality that currently affects over 6 million Americans. This statistic is expected to double over the next decade given the increasing prevalence of AF risk factors such as advanced age and obesity. Atrial fibrillation confers a 5-fold risk of ischemic stroke, but can be treated effectively with anticoagulation therapy. Despite the efficacy of available treatment options, 1 in 5 patients with AF present with stroke as their initial manifestation of the arrhythmia. This is attributable to the significant challenge in diagnosing AF due to its episodic and sometimes asymptomatic nature. Existing AF monitoring strategies are burdensome or costly and invasive, and thus have low patient adherence and satisfaction. Recently, commercially available wrist-based wearable devices, or smartwatches, have shown to be accurate for AF detection, and may represent a promising tool for identifying AF. However, commercial devices are not primarily designed for use by older adults for arrhythmia detection, and there is a significant research gap in the feasibility of using smartwatches for arrhythmia detection in this population. Furthermore, no previous research has investigated the potential for implementation and integration of smartwatches into the healthcare system and infrastructure. Using data collected from the in-house randomized control trial Pulsewatch, and by conducting qualitative assessments in usability and implementation, this proposal addresses the evidence gap in the feasibility of smartwatches for AF detection with three specific aims: 1) to evaluate individual-level factors associated with adherence of using a smartwatch for AF detection, 2) to explore patient characteristics associated with acceptability of smartwatches and identify specific usability challenges and nuances for older adults, and3) to identify barriers and facilitators of implementing smartwatches for use in a clinical setting. We approach the problem with a user-centered focus and apply rigorous and systematic scientific methods in completing these aims. Knowledge generated from this proposal will provide future researchers and stakeholders with practical evidence in the potential use of smartwatches for detection of AF.

Physical frailty, characterized by decreased physiologic reserve and increased vulnerability to stressors, and cognitive impairment, ranging from mild impairment to dementia, often co-occur in older adults. Both are associated with considerable adverse health outcomes, high healthcare costs, and substantial caregiver burden, and are highly prevalent in U.S. community-dwelling older adults. However, for older adults receiving long-term care in nursing homes, data is scarce on the prevalence of the two conditions over their stay. Community-based studies suggest the heterogeneous clinical presentation of physical frailty, which may have implications for its management. It is unknown if such heterogeneity is similar in older nursing home residents and if it is influenced by cognitive impairment. Further, physical frailty and cognitive impairment share risk factors and predict the future onset of one another but the mechanism of this complex interplay remains unclear. Lastly, depression is strongly correlated with both conditions, yet findings regarding the impact of antidepressants on the progression of physical frailty and cognitive impairment are inconsistent. This proposed F99/K00 project seeks to address these gaps by two specific aims with population, longitudinal data, and advanced statistical methods. Aim 1 (dissertation research) focuses on older nursing home residents and will describe the prevalence of physical frailty and cognitive impairment; identify subgroups of physical frailty and examine the variation of subgroups by cognitive impairment levels, and delineate the developmental trajectories of physical frailty and cognitive impairment and examine the correlations between trajectories. Aim2 (post-doctoral research) expands to older adults in the community and will assess the reciprocal association between physical frailty and cognitive impairment; quantify the impact of cumulative exposure to antidepressants on trajectories of physical frailty, cognitive impairment, and depressive symptoms; and examine the effect of depressive symptoms as a mediator of physical frailty on cognitive impairment with causal mediation analysis. Methodological innovations include the use of latent class analysis, group-based trajectory models, structural equation models (autoregressive cross-lagged panel analysis; autoregressive latent trajectory model), and causal mediation. This proposal is directly relevant to the growing aging population in the U.S., including those residing in the nursing homes and those living in the community, since it uses the national nursing home database Minimum Data Set 3.0 (Aim 1) and the nationally representative Health and Retirement Study linked to Medicare Part D Drug Event Files and the Harmonized Cognitive Assessment Protocol (Aim 2). This project will shed light on the concurrent progression of age-related physical and cognitive conditions. Results will inform future work to develop diagnostic tools and prediction models to facilitate timely identification of older adults at risk for accelerated functional decline and implement care tailored to older adults’ needs to effectively delay the onset of negative health outcomes, enhance the quality of life, and foster healthy longevity.

Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (Parent F31-Diversity). Smokers with mental health conditions (MHC) have increased risk of dying from lung and cardiovascular disease. The smoking rate among people with MHC greatly exceeds the rate in the general adult population. Although, these smokers are interested in quitting, their quit rates are much lower than the general population. Factors that act as quitting barriers for these smokers, include pro-smoking social norms and attitudes/behaviors of social network members, underuse of pharmacotherapies and behavioral strategies, and inconsistent treatment of tobacco dependency of mental health providers. Thus, leading researchers have called for innovative approaches to address smoking disparities in people with MHC. Family/peer-based behavioral interventions can be an innovative and effective approach to target smokers with MHC for several reasons. Family/peers influence smoking behaviors, and their importance in health behavior change is well-established. Families/peers are often a principal resource for persons with MHC in seeking and accessing health services. A small but consistent body of literature suggests that family/peers may influence the cessation behavior of smokers with MHC. Family /peers could augment other cessation interventions such as adoption of pharmacotherapies. However, interventions that attempt to harness family/peer support for long-term smoking cessation have underperformed. Knowledge gaps exist in our understanding of the mechanisms through which family/peers affect smoking behaviors, as well as how to involve family/peers in smokers’ cessation efforts. Guided by the social influence domain, as outlined in the Theoretical Domains Framework, my dissertation will address these knowledge gaps. My specific aims are to: 1) prospectively examine the effect of family/peer influences on smoking cessation among smokers with MHC using data from the Population Assessment of Tobacco and Health (PATH study), a nationally representative survey of US non-institutionalized individuals in which participants are interviewed annually, 2) evaluate relationships between smokers’ characteristics, family/peer influences, and smoking cessation among smokers with MHC using Structural Equation Models, and 3) qualitatively explore social and clinical barriers and facilitators to smoking cessation and inclusion of family/peer support among smokers with MHC and mental health care providers. This work in combination with the proposed training will facilitate my development into an independent research scientist committed to conducting research focused on tobacco prevention and control. I will be supported by an outstanding mentoring team with expertise in all the relevant areas: smoking cessation, mental health, implementation science, and biostatistics. My research directly addresses NHLBI’s objective of better understanding the causes of population health differences and identifying strategies to effectively address these differences.

One out of every three children under the age of five in India are undernourished (48 million); to address this crisis, Indian government established a national program from 2005-2012. This study will apply advanced geospatial and multilevel methods to investigate 1) the changes in child undernutrition in India from 2005 to 2012, 2) individual, household, and community level predictors of child undernutrition, and 3) consequences of undernutrition on development during pre-adolescent (8-11) years. Results from this study can guide effective policymaking and implementation of intervention programs.

About 1.2 million Americans are hospitalized annually with acute coronary syndrome (ACS), and most are discharged alive. Although post-ACS mortality and clinical morbidity have been improving patients may be living longer but not better. In fact, many patients suffer substantial declines in quality of life and functional status after discharge with ACS. Because of critical gaps in our understanding how health status evolves over time for ACS patients, important opportunities for prevention and intervention are potentially being missed. The proposed research takes a systematic approach to examining the association of demographic, psychosocial, clinical, and neighborhood factors on trajectories of health-related quality of life after discharge for ACS. Our study will leverage the availability of rich data already collected for the NHLBI-funded TRACE- CORE, a longitudinal prospective cohort study of 2,183 patients hospitalized with ACS. This study includes data from interview, medical record abstraction, linked administrative databases, and geo-coded census tracks. Specific aims are to: (1) Determine associations between individual level socio-economic, clinical, in- hospital and psychosocial factors and trajectories of patient health status post-ACS discharge, both generic (SF-36) and disease specific (Seattle Angina Questionnaire with domains of physical limitations, angina stability, angina frequency, treatment satisfaction and angina specific quality of life); (2) Determine how neighborhood deprivation is associated with trajectories of patient health status; and (3) Identify the extent to which trajectories of generic quality of life and disease-specific quality of life at baseline, one month, 3 months and 6 months predict mortality or readmission 6 months to 1 year post-ACS discharge. This pre-doctoral fellowship proposal also includes a carefully training plan for me to become an independent physician scientist able to fully exploit the potential of patient-reported outcomes to improve the lives of patients with cardiovascular disease.

This proposal has two primary aims: (1) to improve the understanding of the association between patient- reported functional health, comorbidity, and sociodemographic factors and other cause mortality in older men newly diagnosed with prostate cancer; (2) to develop a prototype tool for calculating individualized risk of other cause mortality in this population. Prostate cancer is the most common non-cutaneous cancer in American men and primarily afflicts those age 65 and older. However, most men are diagnosed at early stages with tumors that most often have an indolent course. Guidelines recommend that patients only pursue aggressive treatment if they have >10 year overall life expectancy. Within 5 years of diagnosis, only 11% of American men die due to their prostate cancer, while the majority of patients diagnosed with prostate cancer die of other causes. While validated calculation tools have been developed for clinical use in predicting prostate cancer related mortality, no validated tool has been developed from existing models that identify variables associated with the risk of dying of other causes (OCM). As men in the U.S. live longer and the population above age 65 is rapidly growing, individualized predictions of life expectancy are necessary given the substantial heterogeneity in individual health status. Nearly three quarters of this aging population may have multiple comorbid conditions. Previous work has shown that decrements in patient-reported functional health may be more strongly associated with OCM than the presence of most individual comorbidities. These findings have promise for improving the approach to accounting for the impact of multiple conditions. This predoctoral research training proposal seeks funding to explore the generalizability of prior work demonstrating the association of patient-reported functional health and OCM. The proposed work will help to identify the variables most strongly associated with OCM in older men with prostate cancer, utilizing data from 4,510 subjects in the linked Surveillance Epidemiology and End Results- Medicare Health Outcomes Study (SEER-MHOS) database. This database contains detailed information on cancer characteristics, treatment, cause of death, baseline comorbidities, sociodemographic information, and functional health measures. This proposal will evaluate and improve upon the performance of other cause mortality prediction models through modern statistical techniques to assess predictive model performance. After identifying key predictors of OCM, we propose to develop a prototype clinical risk-calculation tool that estimates personalized risk of 10-year OCM, adapting validated techniques for developing risk calculators. This study will help to establish the utility of patient- reported functional health measures in improving the accuracy of OCM risk estimation in older men newly diagnosed with prostate cancer and will make progress towards a clinically useful OCM risk estimation tool. Completion of this work will help to better identify older patients who would most likely benefit from aggressive treatment vs. those who may not, as they may be more likely to die of other causes.