Faculty Bibliography

BACKGROUND/UNASSIGNED:This study aimed to quantify the association between childhood family environment and longitudinal cardiovascular health (CVH) in adult CARDIA (Coronary Artery Risk Development in Young Adults) Study participants. We further investigated whether the association differs by adult income. METHODS/UNASSIGNED:We applied the CVH framework from the American Heart Association including metrics for smoking, cholesterol, blood pressure, glucose, body mass index, physical activity, and diet. CVH scores (range, 0-14) were calculated at years 0, 7, and 20 of the study. Risky Family environment (range, 7-28) was assessed at year 15 retrospectively, for childhood experiences of abuse, caregiver warmth, and family or household challenges. Complete case ordinal logistic regression and mixed models associated risky family (exposure) with CVH (outcome), adjusting for age, sex, race, and alcohol use. RESULTS/UNASSIGNED:The sample (n=2074) had a mean age of 25.3 (±3.5) years and 56% females at baseline. The median risky family was 10 with ideal CVH (≥12) met by 288 individuals at baseline (28.4%) and 165 (16.3%) at year 20. Longitudinally, for every 1-unit greater risky family, the odds of attaining high CVH (≥10) decreased by 3.6% (OR, 0.9645 [95% CI, 0.94-0.98]). Each unit greater child abuse and caregiver warmth score corresponded to 12.8% lower and 11.7% higher odds of ideal CVH (≥10), respectively (OR, 0.872 [95% CI, 0.77-0.99]; OR, 1.1165 [95% CI, 1.01-1.24]), across all 20 years of follow-up. Stratified analyses by income in adulthood demonstrated associations between risky family environment and CVH remained significant for those of the highest adult income (>$74k), but not the lowest (<$35k). CONCLUSIONS/UNASSIGNED:Although risky family environmental factors in childhood increase the odds of poor longitudinal adult CVH, caregiver warmth may increase the odds of CVH, and socioeconomic attainment in adulthood may contextualize the level of risk. Toward a paradigm of primordial prevention of cardiovascular disease, childhood exposures and economic opportunity may play a crucial role in CVH across the life course.

BACKGROUND:Involving patient and community stakeholders in clinical trials adds value by ensuring research prioritizes patient goals both in conduct of the study and application of the research. The use of stakeholder committees and their impact on the conduct of a multicenter clinical trial have been underreported clinically and academically. The aim of this study is to describe how Study Advisory Committee (SAC) recommendations were implemented throughout the Emergency Medicine Palliative Care Access (EMPallA) trial. EMPallA is a multi-center, pragmatic two-arm randomized controlled trial (RCT) comparing the effectiveness of nurse-led telephonic case management and specialty, outpatient palliative care of older adults with advanced illness. METHODS:A SAC consisting of 18 individuals, including patients with palliative care experience, members of healthcare organizations, and payers was convened for the EMPallA trial. The SAC engaged in community-based participatory research and assisted in all aspects from study design to dissemination. The SAC met with the research team quarterly and annually from project inception to dissemination. Using meeting notes and recordings we completed a qualitative thematic analysis using an iterative process to develop themes and subthemes to summarize SAC recommendations throughout the project's duration. RESULTS:The SAC convened 16 times between 2017 and 2020. Over the course of the project, the SAC provided 41 unique recommendations. Twenty-six of the 41 (63%) recommendations were adapted into formal Institutional Review Board (IRB) study modifications. Recommendations were coded into four major themes: Scientific, Pragmatic, Resource and Dissemination. A majority of the recommendations were related to either the Scientific (46%) or Pragmatic (29%) themes. Recommendations were not mutually exclusive across three study phases: Preparatory, execution and translational. A vast majority (94%) of the recommendations made were related to the execution phase. Major IRB study modifications were made based on their recommendations including data collection of novel dependent variables and expanding recruitment to Spanish-speaking patients. CONCLUSIONS:Our study provides an example of successful integration of a SAC in the conduct of a pragmatic, multi-center RCT. Future trials should engage with SACs in all study phases to ensure trials are relevant, inclusive, patient-focused, and attentive to gaps between health care and patient and family needs. TRIAL REGISTRATION/BACKGROUND:Clinicaltrials.gov Identifier: NCT03325985, 10/30/2017.

INTRODUCTION:Traditional survey-based surveillance is costly, limited in its ability to distinguish diabetes types and time-consuming, resulting in reporting delays. The Diabetes in Children, Adolescents and Young Adults (DiCAYA) Network seeks to advance diabetes surveillance efforts in youth and young adults through the use of large-volume electronic health record (EHR) data. The network has two primary aims, namely: (1) to refine and validate EHR-based computable phenotype algorithms for accurate identification of type 1 and type 2 diabetes among youth and young adults and (2) to estimate the incidence and prevalence of type 1 and type 2 diabetes among youth and young adults and trends therein. The network aims to augment diabetes surveillance capacity in the USA and assess performance of EHR-based surveillance. This paper describes the DiCAYA Network and how these aims will be achieved. METHODS AND ANALYSIS:The DiCAYA Network is spread across eight geographically diverse US-based centres and a coordinating centre. Three centres conduct diabetes surveillance in youth aged 0-17 years only (component A), three centres conduct surveillance in young adults aged 18-44 years only (component B) and two centres conduct surveillance in components A and B. The network will assess the validity of computable phenotype definitions to determine diabetes status and type based on sensitivity, specificity, positive predictive value and negative predictive value of the phenotypes against the gold standard of manually abstracted medical charts. Prevalence and incidence rates will be presented as unadjusted estimates and as race/ethnicity, sex and age-adjusted estimates using Poisson regression. ETHICS AND DISSEMINATION:The DiCAYA Network is well positioned to advance diabetes surveillance methods. The network will disseminate EHR-based surveillance methodology that can be broadly adopted and will report diabetes prevalence and incidence for key demographic subgroups of youth and young adults in a large set of regions across the USA.

BACKGROUND/UNASSIGNED:Ecological momentary assessment (EMA) is an increasingly used tool for data collection in behavioral research, including smoking cessation studies. As previous addiction research suggests, EMA has the potential to elicit cue reactivity by triggering craving and increasing behavioral awareness. However, there has been limited evaluation of its potential influence on behavior. OBJECTIVE/UNASSIGNED:By examining the perspectives of research participants enrolled in a tobacco treatment intervention trial, this qualitative analysis aims to understand the potential impact that EMA use may have had on smoking behaviors that may not have otherwise been captured through other study measures. METHODS/UNASSIGNED:We performed a qualitative analysis of in-depth interviews with participants enrolled in a pilot randomized controlled trial of a tobacco treatment intervention that used SMS text messaging to collect EMA data on smoking behaviors. In the pilot randomized controlled trial, combustible cigarette and e-cigarette use and smoking-related cravings were measured as part of an EMA protocol, in which SMS text messaging served as a smoking diary. SMS text messaging was intended for data collection only and not designed to serve as part of the intervention. After a baseline assessment, participants were asked to record daily nicotine use for 12 weeks by responding to text message prompts that they received 4 times per day. Participants were prompted to share their experiences with the EMA text messaging component of the trial but were not directly asked about the influence of EMA on their behaviors. Transcripts were coded according to the principles of the framework for applied research. The codes were then examined, summarized, and grouped into themes based on the principles of grounded theory. RESULTS/UNASSIGNED:Interviews were analyzed for 26 participants. The themes developed from the analysis suggested the potential for EMA, in the form of an SMS text messaging smoking diary, to influence participants' smoking behaviors. The perceived impacts of EMA text messaging on smoking behaviors were polarized; some participants emphasized the positive impacts of text messages on their efforts to reduce smoking, while others stressed the ways that text messaging negatively impacted their smoking reduction efforts. These contrasting experiences were captured by themes reflecting the positive impacts on smoking behaviors, including increased awareness of smoking behaviors and a sense of accountability, and the negative impacts on emotions and smoking behaviors, including provoking a sense of guilt and triggering smoking behaviors. CONCLUSIONS/UNASSIGNED:The collection of EMA smoking behavior data via SMS text messaging may influence the behaviors and perceptions of participants in tobacco treatment interventions. More research is needed to determine the magnitude of impact and mechanisms, to account for the potential effects of EMA. A broader discussion of the unintended effects introduced by EMA use is warranted among the research community.

Heart failure (HF) causes substantial morbidity and mortality but its pathobiology is incompletely understood. The proteome is a promising intermediate phenotype for discovery of novel mechanisms. We measured 4877 plasma proteins in 13,900 HF-free individuals across three analysis sets with diverse age, geography, and HF ascertainment to identify circulating proteins and protein networks associated with HF development. Parallel analyses in Atherosclerosis Risk in Communities study participants in mid-life and late-life and in Trøndelag Health Study participants identified 37 proteins consistently associated with incident HF independent of traditional risk factors. Mendelian randomization supported causal effects of 10 on HF, HF risk factors, or left ventricular size and function, including matricellular (e.g. SPON1, MFAP4), senescence-associated (FSTL3, IGFBP7), and inflammatory (SVEP1, CCL15, ITIH3) proteins. Protein co-regulation network analyses identified 5 modules associated with HF risk, two of which were influenced by genetic variants that implicated trans hotspots within the VTN and CFH genes.

BACKGROUND:The increasing relevance of substance use disorder (SUD) within the Asian American, Native Hawaiian, and Pacific Islander (AA&NH/PI) communities, particularly amidst rising anti-Asian hate incidents and the disproportionate health and economic challenges faced by the NH/PI community during the COVID-19 pandemic, underscores the urgency of understanding substance use patterns, treatment disparities, and outcomes. METHODS:Following PRISMA guidelines, 37 out of 231 studies met the search criteria. Study characteristics, study datasets, substance use rates, SUD rates, treatment disparities, treatment quality, completion rates, and analyses disaggregated by the most specific AA&NH/PI ethnic group reported were examined. RESULTS:Despite increased treatment admissions over the past two decades, AA&NH/PI remain underrepresented in treatment facilities and underutilize SUD care services. Treatment quality and completion rates are also lower among AA&NH/PI. Analyses that did not disaggregate AA and NHPI as distinct groups from each other or that presented aggregate data only within AA or NHPI as a whole were common, but available disaggregated analyses reveal variations in substance use and treatment disparities among ethnic groups. There is also a lack of research in exploring within-group disparities, including specific case of older adults and substance use. CONCLUSION/CONCLUSIONS:To address disparities in access to substance use treatment and improve outcomes for AA&NH/PI populations, targeted interventions and strategic data collection methods that capture diverse ethnic groups and languages are crucial. Acknowledging data bias and expanding data collection to encompass multiple languages are essential for fostering a more inclusive approach to addressing SUD among AA&NH/PI populations.

Obesity in children remains a major public health problem, with the current prevalence in youth ages 2-19 years estimated to be 19.7%. Despite progress in identifying risk factors, current models do not accurately predict development of obesity in early childhood. There is also substantial individual variability in response to a given intervention that is not well understood. On April 29-30, 2021, the National Institutes of Health convened a virtual workshop on "Understanding Risk and Causal Mechanisms for Developing Obesity in Infants and Young Children." The workshop brought together scientists from diverse disciplines to discuss (1) what is known regarding epidemiology and underlying biological and behavioral mechanisms for rapid weight gain and development of obesity and (2) what new approaches can improve risk prediction and gain novel insights into causes of obesity in early life. Participants identified gaps and opportunities for future research to advance understanding of risk and underlying mechanisms for development of obesity in early life. It was emphasized that future studies will require multi-disciplinary efforts across basic, behavioral, and clinical sciences. An exposome framework is needed to elucidate how behavioral, biological, and environmental risk factors interact. Use of novel statistical methods may provide greater insights into causal mechanisms.

IMPORTANCE:Equity is an essential domain of health care quality. The Centers for Medicare & Medicaid Services (CMS) developed 2 Disparity Methods that together assess equity in clinical outcomes. OBJECTIVES:To define a measure of equitable readmissions; identify hospitals with equitable readmissions by insurance (dual eligible vs non-dual eligible) or patient race (Black vs White); and compare hospitals with and without equitable readmissions by hospital characteristics and performance on accountability measures (quality, cost, and value). DESIGN, SETTING, AND PARTICIPANTS:Cross-sectional study of US hospitals eligible for the CMS Hospital-Wide Readmission measure using Medicare data from July 2018 through June 2019. MAIN OUTCOMES AND MEASURES:We created a definition of equitable readmissions using CMS Disparity Methods, which evaluate hospitals on 2 methods: outcomes for populations at risk for disparities (across-hospital method); and disparities in care within hospitals' patient populations (within-a-single-hospital method). EXPOSURES:Hospital patient demographics; hospital characteristics; and 3 measures of hospital performance-quality, cost, and value (quality relative to cost). RESULTS:Of 4638 hospitals, 74% served a sufficient number of dual-eligible patients, and 42% served a sufficient number of Black patients to apply CMS Disparity Methods by insurance and race. Of eligible hospitals, 17% had equitable readmission rates by insurance and 30% by race. Hospitals with equitable readmissions by insurance or race cared for a lower percentage of Black patients (insurance, 1.9% [IQR, 0.2%-8.8%] vs 3.3% [IQR, 0.7%-10.8%], P < .01; race, 7.6% [IQR, 3.2%-16.6%] vs 9.3% [IQR, 4.0%-19.0%], P = .01), and differed from nonequitable hospitals in multiple domains (teaching status, geography, size; P < .01). In examining equity by insurance, hospitals with low costs were more likely to have equitable readmissions (odds ratio, 1.57 [95% CI, 1.38-1.77), and there was no relationship between quality and value, and equity. In examining equity by race, hospitals with high overall quality were more likely to have equitable readmissions (odds ratio, 1.14 [95% CI, 1.03-1.26]), and there was no relationship between cost and value, and equity. CONCLUSION AND RELEVANCE:A minority of hospitals achieved equitable readmissions. Notably, hospitals with equitable readmissions were characteristically different from those without. For example, hospitals with equitable readmissions served fewer Black patients, reinforcing the role of structural racism in hospital-level inequities. Implementation of an equitable readmission measure must consider unequal distribution of at-risk patients among hospitals.

STUDY QUESTION/OBJECTIVE:What structural (logistical) and psychological challenges do patients who cryopreserve oocytes or embryos for medical reasons face, including possible barriers to using their frozen materials? SUMMARY ANSWER/CONCLUSIONS:The majority of women who underwent oocyte or embryo cryopreservation for medical reasons reported a desire to use their frozen oocytes or embryos but had been impeded by ongoing medical issues, the need for a gestational carrier, or the lack of a partner. WHAT IS KNOWN ALREADY/BACKGROUND:Current data suggest that many women who have frozen oocytes or embryos for medical indications are concerned about the prospect of infertility and have unique emotional and financial needs that differ from patients with infertility. Further, most patients have not returned to use their cryopreserved materials. STUDY DESIGN, SIZE, DURATION/METHODS:This is a qualitative interview study of 42 people who cryopreserved between January 2012 and December 2021. Interviews were conducted between March 2021 and March 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:All participants were cisgender women who had undergone oocyte or embryo cryopreservation for medical indications at an academic fertility center. Participants were invited to interview by email if they were younger than 40 years old when their oocytes or embryos were cryopreserved. Interviews were conducted over the internet and transcribed verbatim. Data were analyzed using thematic analysis with the constant comparison method. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:Saturation was reached at 42 interviews. The median age of participants was 35 years old (range 28-43) at interview and 31 years old (range 25-39) at cryopreservation. Of the 42 women, 30 had a cancer diagnosis, while 7 had non-cancer chronic medical conditions, and 5 had hereditary cancer susceptibility syndromes. There were 12 women who banked embryos and 30 who banked oocytes. The majority of women indicated a desire to use their cryopreserved materials, but many were unsure about how or when. Four had already used their frozen oocytes or embryos, while another four had conceived without assisted reproduction. The cryopreservation experience was described by the majority as highly emotionally challenging because they felt out of place among couples receiving infertility treatment and, for cancer patients, overwhelmed by the complex decisions to be made in a short time period. Common reported barriers to using frozen materials included ongoing medical issues preventing pregnancy, the need for a gestational carrier, the lack of a partner, and the desire for unassisted conception. Some were glad to have frozen oocytes or embryos to allow more time to meet a partner or if they were considering becoming single parents. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The majority of participants had their oocytes or embryos frozen at a single, urban, academic fertility center, which may limit generalizability. We also could not calculate a response rate because the snowball technique was used to identify additional participants, so did not know the total number of people invited to participate. Like other interview studies, our study may be subject to response bias because those who agreed to participate may have particularly positive or negative views about their experiences. Furthermore, the mean follow-up time since freezing was relatively short (3.3 years, median 2.7 years), which may not have been enough time for some patients to use their frozen materials. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:Learning about the experiences of patients undergoing medically indicated oocyte and embryo cryopreservation can help clinicians better counsel these patients regarding decisions and hurdles they may encounter. We found that most patients had not returned to use their frozen materials because of ongoing medical issues, the need for a gestational carrier, lack of a partner, or the desire to attempt unassisted reproduction. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:This study did not receive any funding. The authors of this study have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER/BACKGROUND:N/A.

STUDY QUESTION/OBJECTIVE:Do children born to mothers with polycystic ovary syndrome (PCOS) have an adverse cardiometabolic profile including arterial stiffness at 9 years of age compared to other children? SUMMARY ANSWER/CONCLUSIONS:Children of mothers with PCOS did not have differing cardiometabolic outcomes than children without exposure. WHAT IS KNOWN ALREADY/BACKGROUND:While women with PCOS themselves have higher risk of cardiometabolic conditions such as obesity and diabetes, the evidence on intergenerational impact is unclear. Given in utero sequalae of PCOS (e.g. hyperandrogenism, insulin resistance), the increased risk could be to both boys and girls. STUDY DESIGN, SIZE, DURATION/METHODS:The Upstate KIDS cohort is a population-based birth cohort established in 2008-2010 to prospectively study the impact of infertility treatment on children's health. After ∼10 years of follow-up, 446 mothers and their 556 children attended clinical visits to measure blood pressure (BP), heart rate, arterial stiffness by pulse wave velocity (PWV), mean arterial pressure, lipids, high-sensitivity C-reactive protein (hsCRP), hemoglobin A1c (HbA1c), and anthropometrics. PARTICIPANTS/MATERIALS, SETTING, METHODS/METHODS:Women self-reported ever diagnoses of PCOS ∼4 months after delivery of their children in 2008-2010. Linear regression models applying generalized estimating equations to account for correlation within twins were used to examine associations with each childhood cardiometabolic outcome. MAIN RESULTS AND THE ROLE OF CHANCE/RESULTS:In this cohort with women oversampled on infertility treatment, ∼14% of women reported a PCOS diagnosis (n = 61). We observed similarities in BP, heart rate, PWV, lipids, hsCRP, HbA1c, and anthropometry (P-values >0.05) among children born to mothers with and without PCOS. Associations did not differ by child sex. LIMITATIONS, REASONS FOR CAUTION/CONCLUSIONS:The sample size of women with PCOS precluded further separation of subgroups (e.g. by hirsutism). The population-based approach relied on self-reported diagnosis of maternal PCOS even though self-report has been found to be valid. Participants were predominantly non-Hispanic White and a high proportion were using fertility treatment due to the original design. Differences in cardiometabolic health may be apparent later in age, such as after puberty. WIDER IMPLICATIONS OF THE FINDINGS/CONCLUSIONS:Our results provide some reassurance that cardiometabolic factors do not differ in children of women with and without self-reported PCOS during pregnancy. STUDY FUNDING/COMPETING INTEREST(S)/BACKGROUND:Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (contracts #HHSN275201200005C, #HHSN267200700019C, #HHSN275201400013C, #HHSN275201300026I/27500004, #HHSN275201300023I/27500017). The authors have no conflicts of interest. REGISTRATION NUMBER/BACKGROUND:NCT03106493.