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Abstract P1070: Predictors of Non-Arrival at Initial Study Screening Visits among Black Adults: Data from the GoFresh Trials
Introduction: Trial recruitment is a major determinant of study success and participants’ non-arrival at screening visits represents a significant barrier to timely and representative study completion. However, little is known about the participant and study process characteristics associated with non-arrival at study visits. Objective: To investigate factors associated with non-arrival at initial in-person screening visits in two ongoing randomized controlled trials. Methods: The Groceries For Black Residents of Boston to Stop Hypertension trials (GoFresh and GoFreshRx) study whether home-delivered DASH-patterned groceries can reduce blood pressure among Black adults in communities characterized by lower median income. In this analysis, we examined sociodemographic and study-related factors potentially associated with participant non-arrival at their initial study visit (defined as rescheduling or not showing up at all). Associations were determined using logistic regression with adjustment for age, sex, and hypertension treatment status. Results: Among 1152 participants, the non-arrival rate was 37%. Older participants, those with smaller families, less socially vulnerable participants (participants in the 2 nd and 3 rd quartiles of the Social Vulnerability Index), participants informed via mailed brochures, and participants with a shorter time between initial contact and first scheduled visit were more likely to arrive at their initial visits ( Table 1 ). Participant method of contacting the study (e.g. filling out a survey, calling a study-affiliated number, emailing a study-affiliated email address), visit time (Thursday vs. Friday; AM vs. PM), and season of visit were not associated with visit non-arrival. Conclusion: In this large trial recruitment drive, we identified several participant and study process characteristics associated with non-arrival at screening visits. These factors represent potential targets for future intervention studies that either accommodate patient factors or intervene upon study process barriers to achieve timely and representative recruitment goals.
Abstract P1048: Are Helpful Kids Healthy Kids? A Systematic Review of Prosocial Behavior in Childhood and Adolescence in Relation to Cardiometabolic Outcomes
Introduction: Prosociality involves behaving in a way that benefits others such as helping, cooperating, and volunteering. Prosocial behavior in adults is associated with better health and longevity, but it is unclear if health benefits begin to manifest in early life. This preregistered systematic review investigated the hypothesis that prosociality in children and adolescents is associated with healthier cardiometabolic outcomes across the life course. Methods: In October 2023, we searched PubMed and PsycINFO databases for studies written in English with healthy individuals <18 years old, a childhood or adolescent assessment of prosocial behavior, and ≥1 cardiometabolic outcome (e.g., blood pressure, lipids, blood glucose, body mass index [BMI]). We identified 9,744 records, from which 168 duplicates were removed. Two researchers screened the titles and abstracts of 9,576 records, from which 163 full texts were reviewed. This resulted in ten studies included in the review. One researcher extracted data from each study and assessed the quality based on nine criteria (e.g., study design, validated assessments, accounting for confounders). Findings were synthesized in a narrative review. Results: Included studies were comprised of up to 22,771 participants. Five were cross-sectional, four had longitudinal designs, and one was an experiment. The mean quality score for the included studies was 5.5 (SD = 0.97; possible range 1-9). Prosocial behavior was typically measured in mid-childhood or adolescence using the parent-reported prosocial subscale of the Strengths and Difficulties Questionnaire. Cardiometabolic outcomes were objectively assessed in all studies. BMI was the primary cardiometabolic outcome in nine of the ten studies, but most reported null associations between prosociality and BMI. Only four studies considered other outcomes. The most promising findings came from an intervention in which adolescents were randomly assigned to volunteer or be in a wait list control condition; adolescents who volunteered had lower post-intervention levels of inflammation, total cholesterol, and BMI. Conclusions Given the few studies evaluating prosocial behavior in youth and the nearly exclusive focus on BMI, we cannot draw firm conclusions as to whether greater prosociality in youth is related to better cardiometabolic health. More research on prosocial behavior in early life is warranted given its purported benefits for both the recipient and the giver.
Compositional modeling of solution gas–oil ratio (Rs): a comparative study of tree-based models, neural networks, and equations of state
Psychological booster shots targeting memory increase long-term resistance against misinformation
Abstract An increasing number of real-world interventions aim to preemptively protect or inoculate people against misinformation. Inoculation research has demonstrated positive effects on misinformation resilience when measured immediately after treatment via messages, games, or videos. However, very little is currently known about their long-term effectiveness and the mechanisms by which such treatment effects decay over time. We start by proposing three possible models on the mechanisms driving resistance to misinformation. We then report five pre-registered longitudinal experiments ( N total = 11,759) that investigate the effectiveness of psychological inoculation interventions over time as well as their underlying mechanisms. We find that text-based and video-based inoculation interventions can remain effective for one month—whereas game-based interventions appear to decay more rapidly—and that memory-enhancing booster interventions can enhance the diminishing effects of counter-misinformation interventions. Finally, we propose an integrated memory-motivation model, concluding that misinformation researchers would benefit from integrating knowledge from the cognitive science of memory to design better psychological interventions that can counter misinformation durably over time and at-scale.
Abstract P3068: Impact of the Delta index, a Measure of Residential Segregation, on Hypertension Risk Among Black and White Women and Men
Background: Hypertension remains a significant public health concern, with persistent racial and gender disparities in disease burden. Residential segregation limits people’s access to resources that could promote health. We sought to investigate racial and gender differences in the association of residential segregation and risk of incident hypertension. Methods: This analysis included Black and White participants of the REasons for Geographic And Racial Differences in Stroke study (30,239 Black and White adults from the 48 contiguous US states) who did not have hypertension at the first visit (2003-7) and completed the 2 nd visit (2013-16). County-level residential segregation was measured with the delta index, where higher scores indicate greater racial segregation. The delta index measures the concentration dimension, which depicts the relative amount of space occupied by Black people in an area. Modified Poisson regression was used to calculate risk ratios (RRs) of incident hypertension per 1-standard deviation (SD) increment delta index. Models were adjusted for age, gender, and systolic blood pressure. Racial and gender differences in the association of the delta index and hypertension risk were tested. Results: Among the 6,894 participants, the mean (SD) age was 62 (8.4) years. The incidence of hypertension was 48% for Black women, 43% for Black men, 32% White women, and 34% White men. The risk of hypertension was 3% lower for each SD higher delta index (RR: 0.97; 95% [confidence interval] CI: 0.94-0.99). There were significant racial and gender differences in the association of the delta index and hypertension risk (Table). Black women had a 9% lower risk of hypertension per SD higher delta index (RR: 0.91; 95% CI: 0.85-0.96). The association was not significant for the other race-gender groups. Conclusions: Our findings revealed that delta index was associated with lower risk of hypertension in Black women. Given that previous research generally reports positive associations between residential segregation and health outcomes, we need to investigate mechanisms in segregated areas that explain this negative association between the delta index and hypertension risk.
Abstract P3038: Height Shortening from Midlife to Late-life and Subsequent Risk of Cardiovascular Outcomes: the Atherosclerosis Risk in Communities (ARIC) Study
Background: Studies have suggested that height shortening over a few decades may be associated with adverse health outcomes, but its association with subsequent risk of cardiovascular disease (CVD) is unknown. Hypothesis: Height shortening over ~25 years is heterogeneous across individuals and greater shortening is independently associated with incident CVD. Methods: We characterized height shortening from age 44 to 90 with mixed-effects models for 15,672 men and women using data from ARIC visit 1 (N=15,774, age 44-66 years in 1987-89) through visit 5 (N=6,520, age 66-90 years in 2011-13) after excluding 102 participants with outliers of height shortening (defined as >3 SD ). Then, we used multivariable Cox proportional hazards models to quantify associations between measured height shortening from visit 1 to visit 5 with subsequent risk of CVD (coronary heart disease [178 cases], stroke [173 cases], and heart failure [299 cases]) and all-cause mortality (1,012 deaths) over a mean follow-up of 8.3 years among 3,858 participants free of CVD at visit 5. CVD outcomes were adjudicated by physician panels. Results: Estimated height shortening from age 44 to 90 was greater in women than men (-6.7 cm vs. -6.2 cm), despite their lower average height (162.3 cm vs 176.1 cm) at visit 1. Height shortening from visit 1 to visit 5 over ~25 years ranged from +3 (increase) to -9 cm across our study population. There was a dose-response relationship between greater height shortening and all outcomes of interest except stroke, independent of demographics and traditional CVD risk factors (Table). Coronary heart disease had the strongest association with height shortening (hazard ratio in Model 2, 2.11 [95%CI 1.40-3.10] for Q4, 1.71 [1.12-2.61] for Q3, and 1.19 [0.78-1.80] for Q2 vs. Q1). Conclusions: Height declines on average ~6-7 cm from age 44 to 90 in men and women, and greater height shortening is independently associated with higher risk of CVD and mortality. Our results support the use of height shortening as a health parameter for gauging CVD risk.
Abstract MP04: Association of Mediterranean Diet Score Components with Weight Loss: Findings from the MAINTAIN PRIME Study
Introduction: Caloric intake and diet quality are important for weight management. This study leverages data from the MAINTAIN PRIME weight maintenance trial, which recruited participants with recent, intentional weight loss ≥ 5%. We analyzed the association between diet quality and percentage weight loss at study enrollment. Methods: We assessed diet quality with the Mediterranean Diet Score (MDS), a validated 14-item survey, and examined individual components, each with 2 or 3 categorical levels. The association between percentage weight loss and MDS components was analyzed using gamma regression with log link across three models: Model 1 controlled for gender, Model 2 for gender and weight loss medication use, and Model 3 for gender, medication use, and education. Rate ratios (RR) and 95% confidence intervals (CI) were calculated for each MDS component. Results: Baseline weight and Mediterranean Diet Score (MDS) data were collected from 262 participants. Adjusted RR values for each component of the MDS are found in Table 1. Key findings include: Commercial pastries (cookies, cakes, etc.) The RR of 0.89 across all models (p <0.01), suggests a clear association between consuming more commercial pastries and less weight loss. Those who consume more are likely to experience about 11% less weight loss compared to those who consume less or none. Carbonated or sugar-sweetened beverages (CSSB): The RR of 0.90 across all three models (p ≤ 0.01) suggests that individuals who consume more CSSB experience 10% less weight loss compared to those who consume fewer or no CSSB. Nuts: The RR of 0.89–0.90 across all models (p = 0.01) indicates that a higher intake of nuts per week is associated with less weight loss. Red meat: Across the models, a higher red meat consumption was associated with less weight loss. While the association is not statistically significant in Model 1 (p = 0.11), it becomes significant in Model 2 (p = 0.03) and Model 3 (p = 0.02). Therefore, adjusting for additional variables strengthens the observed association. In Model 3, the RR of 0.91 indicates 9% less weight loss compared to those with lower or no red meat intake. Conclusions: A higher consumption of commercial pastries, carbonated or sugar-sweetened beverages, nuts, and red meat was negatively associated with less weight loss, highlighting their potential role in hindering weight loss efforts. Our findings highlight the importance of diet quality management.
Vaginal microbiota transplantation alleviates vaginal atrophy in ovariectomized mice
Atlas of imprinted and allele-specific DNA methylation in the human body
Abstract P3067: State Adoption of Paid Sick Leave and Cardiovascular Disease Mortality Among Adults Aged 15-64 in the United States, 2008 to 2019
Cardiovascular Disease (CVD) is the leading cause of death in the United States and may be prevented through improved working conditions. The United States does not guarantee paid sick leave (PSL) at the federal level. Our objective was to examine the relationship between state-level PSL policies and CVD mortality. We used quasi-experimental event study methods proposed by Sun and Abraham to examine the relationship between implementing a mandatory PSL policy for all employees at the state-level and county-level CVD mortality among working-age adults aged 15 to 64 over time from 2008 to 2019. We examined the annual CVD mortality rates (2008-2019) in 1054 counties from all 50 states and Washington D.C., accounting for approximately 88% of the United States population. We found that in the Northeastern region of the United States, there were drops in the CVD mortality rate for persons ages 15-64 for all years after PSL was adopted, ranging from 6.0 fewer deaths per 100,000 persons (β=-6.0, 95% CI = -10.1, -1.9) seven years post-treatment to 2.9 fewer deaths three years post-treatment (β=-2.9, 95% CI= -4.9, -0.9). We found no effect of PSL in the Western United States, and mixed effects in a nationwide analysis. Finally, the strong presence of pretreatment effects in the Western United States makes the results for that region uninterpretable. Our results support the use of state-level PSL policies to reduce county-level CVD mortality rates in the Northeastern United States.
Abstract P3142: Moderating Role of Psychosocial Risk and Resilience in the Relationship Between Neighborhood Disadvantage and Incident Cardiovascular Disease Across Ethnoracial Groups: MESA Cohort 2000-2019
Introduction: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in the U.S., with neighborhood disadvantage as a well-established risk factor. Emerging evidence indicates a role for psychosocial risk and resilience factors in influencing these relationships, but the interplay between environmental and psychosocial factors across ethnoracial groups is poorly understood. This study examined whether psychosocial factors moderated the relationship between neighborhood disadvantage and person-level incident CVD in a multiracial, multiethnic cohort. Methods: We examined data from 4,326 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who were free of CVD at baseline and were assessed between July 17, 2000 and February 4, 2012. The exposure was neighborhood disadvantage quantified by the Area Deprivation Index. Moderators were optimism measured by the Life Orientation Test revised and anger measured by the State-Trait Anger Expression Inventory which includes subscales state anger, trait anger temperament, and trait anger reaction. We used covariate-adjusted, cause-specific, multilevel Cox models to generate hazard ratios and 95% CI for four self-identified ethnoracial groups—Black, Chinese, Hispanic/Latino[g1] , and White. Results: Mean age at baseline was 62.6 years old (10.0 SD) and 53.2% of participants were female. Only among Black participants did higher optimism levels mitigate the effect of neighborhood disadvantage on incident CVD ( Figure 1 ). In Black and Hispanic/Latino participants, higher levels of state anger and trait anger reactivity magnified the association between neighborhood disadvantage and incident CVD, while among Chinese participants, a more angry temperament exhibited a similar effect. The interaction between environmental and psychosocial factors was not statistically significant among White participants. Conclusion: Our findings support the need for CVD interventions that address neighborhood socioeconomic and psychosocial characteristics while considering the sociocultural differences between ethnoracial groups.
Abstract P2020: Alcohol Use and Hypertension in the Eastern Caribbean
Introduction: Hypertension (HTN) and other non-communicable diseases are a leading cause of morbidity and mortality in the Caribbean. The region has high rates of alcohol use and binge drinking which has been associated with adverse health outcomes like HTN. This study aimed to fill evidence gaps on the relationship between binge drinking and HTN in the Eastern Caribbean. Hypothesis: Individuals with binge drinking behaviors have higher prevalence of HTN in the Eastern Caribbean Health Outcomes Research Network (ECHORN) cohort. Methods: We conducted a cross-sectional analysis of data (2013-2018) from the ECHORN Study (n=2961), an ongoing longitudinal study of adults conducted across four island sites. Participants completed a self-reported health survey, underwent laboratory testing and a clinical examination. The main exposure was binge drinking, defined as more than 4 alcoholic beverages for women or 5 for men in a 24-hour period. Covariates included gender, participant age, smoking status, and BMI. The outcome, HTN, was defined using JNC-7 guidelines and operationalized as a binary variable (yes/no) for inclusion in analyses. Chi-Square tests and logistic regression were used for analyses. We examined associations overall and among those under 60 years of age. Results: Analysis included 1142 participants after accounting for skip patterns. Results showed 34 percent of participants reported binge drinking in the last 30 days and 42 percent had HTN. Forty five percent of those who binge drank had HTN compared to 40 percent among those who did not (p=.18). Among those under 60 years, there was a statistically significant difference in HTN prevalence between those who binge drank and those who did not (p=0.02). Aggregate results show that those who binge drank had 53 percent greater odds (CI=1.15-2.03) of HTN compared to those who did not binge drink. Results for participants under 60 showed 63 percent greater odds of HTN compared to those who did not binge drink (CI=1.15-2.31). Conclusion: Findings showed high prevalence of binge drinking in the Eastern Caribbean and that binge drinking is positively associated with higher prevalence of HTN. The stronger association found in younger individuals is consistent with other findings. Further research is warranted to understand factors that contribute to binge drinking in this population given implications for HTN.
Should Total Neoadjuvant Therapy Be the First-Line Treatment for Patients With Locally Advanced Rectal Cancer?
Oxaliplatin-Based Versus Alkylating Agent in Neuroendocrine Tumors According to the O <sup>6</sup> -Methylguanine-DNA Methyltransferase Status: A Randomized Phase II Study (MGMT-NET)
PURPOSE Alkylating agents (ALKY) are the main chemotherapies used for advanced neuroendocrine tumors (NETs). O 6 -Methylguanine-DNA methyltransferase (MGMT) status, as proficient (p) or deficient (d), may predict the response to ALKY. PATIENTS AND METHODS MGMT-NET (ClinicalTrials.gov identifier: NCT03217097 ) was a phase II trial randomly assigning 1:1 for pMGMT or 2:1 for dMGMT-NETs to either ALKY or oxaliplatin (Ox). Inclusion criteria were a confirmed advanced pancreatic, thoracic, or unknown primary NETs with an indication for chemotherapy and tissue available. The primary aim was to detect a difference of 35% between the 3-month objective response rate (ORR) in pMGMT-NETs versus in dMGMT-NETs when treated with ALKY. A biomarker-stratified design was performed to compare ALKY and Ox in the dMGMT and pMGMT strata for the secondary end points. dMGMT was defined using pyrosequencing (PSQ; methylated MGMT ≥9%) and using immunochemistry ( H -score of MGMT <50) when PSQ was not interpretable. RESULTS From October 2018 to October 2021, 105 patients (55 pancreas, 38 thorax, 12 unknown) started either ALKY (n = 62) or Ox (n = 43). The median age was 63 years (range, 30-84), and 59% were males. NETs were G1 (19%), G2 (69%), or G3 (10%). Among patients with interpretable MGMT status, 56.9% (58 of 102) had a dMGMT-NET. The primary end point was not reached; the 3-month ORR was 10 (29.4%) versus 2 (8%), and the odds ratio was 3.5 (0.58-21.16), P = .172. However, best ORR (18 [52.9%] v 3 [11.5%]) and median progression-free survival (14.6 [95% CI, 7.2 to 22.1] v 11.3 [9.4 to 13.2] months) were higher for dMGMT-NETs versus pMGMT-NETs. MGMT status does not seem to affect the Ox efficacy. CONCLUSION Despite the fact that the primary end point was not reached, ALKY has clinical activity in patients with dMGMT-NETs.
Accurate Determinants of Outcome in ALL
Using Cure Models for Trial Analysis and Design
Reply to: Should Total Neoadjuvant Therapy Be the First-Line Treatment for Patients With Locally Advanced Rectal Cancer?
Activation imaging of gold nanoparticles for versatile drug visualization: An <i>in vivo</i> demonstration
Gold nanoparticles (AuNPs) have recently attracted considerable attention as promising drug carriers. In vivo imaging of AuNPs is required to investigate their pharmacokinetics. However, a direct and highly sensitive method has not yet been established. Therefore, we proposed the activation imaging of AuNPs that radioactivates AuNPs and non-invasively visualizes them using the emitted gamma rays. When the stable isotope of gold, 197Au, is irradiated with low-energy neutrons, it changes to radioactive 198Au, which predominantly emits 412-keV gamma rays. In this study, we synthesized [198Au]AuNPs through neutron irradiation and intratumorally injected them into tumor-bearing mice. In vivo imaging was performed using wideband x rays and gamma rays imager, and the distribution of [198Au]AuNPs in the body of mice was observed. Furthermore, we labeled the alpha-emitting therapeutic drug 211At with [198Au]AuNPs. Although 211At itself can be visualized using its 79-keV x rays, the long-term tracking of 211At-labeled AuNPs has been challenging due to its relatively short half-life of 7.2 h. The activation of AuNPs enables the long-term tracking of 211At-labeled AuNPs owing to the 2.7-day half-life of 198Au. 211At-labeled [198Au]AuNPs were injected intravenously into mice and visualized using a wideband x rays and gamma rays imager. Simultaneous imaging of 211At and 198Au was performed on the day of injection and 2 days after injection. Although 211At could no longer be imaged 2 days after injection, the distribution of the drug was visualized using gamma rays from 198Au.
Erratum: Fulvestrant Versus Anastrozole in Endocrine Therapy–Naïve Women With Hormone Receptor–Positive Advanced Breast Cancer: Final Overall Survival in the Phase III FALCON Trial
Development and Validation of the RSClinN+ Tool to Predict Prognosis and Chemotherapy Benefit for Hormone Receptor–Positive, Node-Positive Breast Cancer
PURPOSE Clinicopathological factors and the 21-gene Oncotype DX Breast Recurrence Score (RS) test both influence prognosis. Our goal was to develop a new tool, RSClinN+, to individualize recurrence risk and chemotherapy benefit predictions by menopausal status for patients with HR+/human epidermal growth factor receptor 2–negative, lymph node–positive breast cancer by integrating the RS result with clinicopathological factors (grade, tumor size, age). METHODS We used patient-level data from 5,283 patients treated with chemoendocrine therapy (CET) versus endocrine therapy alone (ET) in the S1007 (N = 4,916) and S8814 (N = 367) trials to develop the tool. Cox proportional hazards regression models stratified by trial were used to estimate 5-year invasive disease-free survival for pre- and postmenopausal woman, respectively. The integrated RSClinN+ model was compared with RS alone and clinicopathological models using likelihood ratio tests. Absolute CET benefit was estimated as the difference between ET and CET risk estimates. Validation of RSClinN+ was performed in 592 patients with node-positive disease in the Clalit Health Services registry. RESULTS RSClinN+ provides better prognostic information than RS model alone (premenopausal P = .034; postmenopausal P < .001) or clinicopathological model alone (premenopausal P = .002; postmenopausal, P < .001). In postmenopausal women, RS showed interaction with CET benefit ( P = .016), with RSClinN+ absolute CET benefit ranging from <0.1% to 21.5% over RS ranges 0-50. In premenopausal patients with RS ≤25, there was no significant interaction between RS and CET benefit. In external validation, RSClinN+ risk estimates were prognostic (hazard ratio, 1.75 [95% CI, 1.38 to 2.20]) and concordant with observed risk (Lin's concordance, 0.92). CONCLUSION RSClinN+ provides improved estimates of prognosis and absolute CET benefit for individual patients compared with RS or with clinical data alone and could be used in patient counseling.