Faculty Bibliography

INTRODUCTION/UNASSIGNED:South Asian adults are at high risk for atherosclerotic cardiovascular disease, for which coronary artery calcification is an early predictor. Adherence to the Dietary Approaches to Stop Hypertension diet is a modifiable risk factor that may mitigate the progression of coronary artery calcification and atherosclerotic cardiovascular disease. METHODS/UNASSIGNED:Using data from the Mediators of Atherosclerosis in South Asians Living in America cohort, the authors calculated a Dietary Approaches to Stop Hypertension dietary score (categorized as low, moderate, and high) to examine the associations of Dietary Approaches to Stop Hypertension diet adherence with coronary artery calcification after a 5-year follow up. RESULTS/UNASSIGNED:The authors found that participants in the high Dietary Approaches to Stop Hypertension category were 41% less likely to have coronary artery calcification score >100 (age-adjusted incidence rate ratio=0.59; 95% CI=0.36, 0.95) than those in the low category; this association was attenuated in multivariable models. Differences were observed by sex. Men in the high Dietary Approaches to Stop Hypertension category were 51% less likely to have coronary artery calcification score >100 (adjusted incidence rate ratio=0.49; 95% CI=0.26, 0.95) and experienced 0.46-fold coronary artery calcification change (fold change=0.46; 95% CI=0.18, 0.90) in multivariable models. CONCLUSIONS/UNASSIGNED:The findings indicate a relationship between Dietary Approaches to Stop Hypertension diet and early predictors of atherosclerotic cardiovascular disease risk among South Asians living in the U.S., particularly men.

South Asians are among the fastest-growing immigrant population group in the United States (U.S.) with a unique disease risk profile. Due in part to immigration and acculturation factors, South Asians engage differently with behavioural risk factors (e.g. smoking, alcohol intake, physical activity, sedentary behaviour, and diet) for hypertension, which may be modified for the primary prevention of cardiovascular disease. Using data from the Mediators of Atherosclerosis in South Asians Living in America cohort, we conducted a cross-sectional analysis to evaluate the association between behavioural risk factors for cardiovascular disease and diet. We created a behavioural risk factor score based on smoking status, alcohol consumption, physical activity, and TV watching. We also calculated a Dietary Approaches to Stop Hypertension (DASH) dietary score based on inclusion of relevant dietary components. We used both scores to examine the association between engaging with risk factors for hypertension and the DASH diet among a cohort of South Asian adults. We found that participants with 3-4 behavioural risk factors had a DASH diet score that was 3 units lower than those with no behavioural risk factors (aβ: -3.25; 95% CI: -4.28, -2.21) and were 86% less likely to have a DASH diet score in the highest category compared to the lowest DASH diet score category (aOR: 0.14; 95% CI: 0.05, 0.37) in the fully adjusted models. These findings highlight the relationship between behavioural risk factors for hypertension among South Asians in the U.S.

High blood pressure is an important predictor of atherosclerotic cardiovascular disease (ASCVD), particularly among South Asians, who are at higher risk for ASCVD when compared to other population groups. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is established as the best proven nonpharmacological approach to preventing hypertension in adults. Using data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we calculated a DASH dietary score to examine the association between adherence to the DASH diet and its components, and prevalent and incident hypertension and systolic and diastolic blood pressure, after five years of follow-up. We found that the relative risk ratio (RRR) of incident hypertension was 67% lower among participants in the highest DASH diet score category (aRRR: 0.33; 95% CI: 0.13, 0.82; p_trend = 0.02) compared with those in the lowest DASH diet score category in fully adjusted models. These findings are consistent with previous clinical trials and large prospective cohort studies, adding to evidence that supports the diet-disease relationship established between DASH diet and hypertension. This study is the first to examine DASH diet adherence and hypertension among South Asian adults in the U.S.

IMPORTANCE:There is a disproportionately greater burden of COVID-19 among Hispanic and non-Hispanic Black individuals, who also experience poorer cancer outcomes. Understanding individual-level and area-level factors contributing to inequities at the intersection of COVID-19 and cancer is critical. OBJECTIVE:To evaluate associations of individual-level and area-level social determinants of health (SDOH) with delayed or discontinued cancer treatment following SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS:This retrospective, registry-based cohort study used data from 4768 patients receiving cancer care who had positive test results for SARS-CoV-2 and were enrolled in the American Society for Clinical Oncology COVID-19 Registry. Data were collected from April 1, 2020, to September 26, 2022. EXPOSURES:Race and ethnicity, sex, age, and area-level SDOH based on zip codes of residence at the time of cancer diagnosis. MAIN OUTCOMES AND MEASURES:Delayed (≥14 days) or discontinued cancer treatment (any cancer treatment, surgery, pharmacotherapy, or radiotherapy) and time (in days) to restart pharmacotherapy. RESULTS:A total of 4768 patients (2756 women [57.8%]; 1558 [32.7%] aged ≥70 years at diagnosis) were included in the analysis. There were 630 Hispanic (13.2%), 196 non-Hispanic Asian American or Pacific Islander (4.1%), 568 non-Hispanic Black (11.9%), and 3173 non-Hispanic White individuals (66.5%). Compared with non-Hispanic White individuals, Hispanic and non-Hispanic Black individuals were more likely to experience a delay of at least 14 days or discontinuation of any treatment and drug-based treatment; only estimates for non-Hispanic Black individuals were statistically significant, with correction for multiple comparisons (risk ratios [RRs], 1.35 [95% CI, 1.22-1.49] and 1.37 [95% CI, 1.23-1.52], respectively). Area-level SDOH (eg, geography, proportion of residents without health insurance or with only a high school education, lower median household income) were associated with delayed or discontinued treatment. In multivariable Cox proportinal hazards regression models, estimates suggested that Hispanic (hazard ratio [HR], 0.87 [95% CI, 0.71-1.05]), non-Hispanic Asian American or Pacific Islander (HR, 0.79 [95% CI, 0.46-1.35]), and non-Hispanic Black individuals (HR, 0.81 [95% CI, 0.67-0.97]) experienced longer delays to restarting pharmacotherapy compared with non-Hispanic White individuals. CONCLUSIONS AND RELEVANCE:The findings of this cohort study suggest that race and ethnicity and area-level SDOH were associated with delayed or discontinued cancer treatment and longer delays to the restart of drug-based therapies following SARS-CoV-2 infection. Such treatment delays could exacerbate persistent cancer survival inequities in the United States.

PURPOSE/OBJECTIVE:Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C. METHODS:) Day 3 in 21-day cycles. In Group 3, patients received AC Day 1 plus V Days 1-7, and in Group 4, AC Day 1 plus V Days 1-14 was given in 21-day cycles to evaluate effects on γH2AX foci. RESULTS:Eighty patients were enrolled. MTD was not reached for V and C. MTD for V and AC was V 100 mg every 12 h Days 1-4 with AC (60/600 mg/m2) Day 3 every 21 days. V PK appears to be dose-dependent and has no effect on the PK of C. Overall, neutropenia and anemia were the most common adverse events. Objective response in V and AC treated groups was 22% (11/49). Overall clinical benefit rate was 31% (25/80). PAR decreased in PBMCs. Percentage of γH2AX-positive CTCs increased after treatment with V and AC. CONCLUSION/CONCLUSIONS:V and AC can be safely combined. Activity was observed in patients with metastatic breast cancer.

OBJECTIVE:To determine the effect of adding a video and text messages to Reach Out and Read (ROR) on parent-reported literacy activities compared to the standard version. STUDY DESIGN/METHODS:We conducted a mixed methods hybrid type I effectiveness-implementation randomized trial in a community health center that serves low-income Latino families. We assessed shared reading frequency and the StimQ Reading subscale, at enrollment and 6-month follow-up and the StimQ Parent Verbal Responsivity subscale, Parent Reading Belief Inventory, and Survey of Wellbeing of Young Children-Milestones at follow-up. We randomized 160 parent-child dyads to ROR or ROR plus video and text messages (enhanced ROR). We collected process data on ROR and engagement with texts. We interviewed 15 enhanced ROR participants. We analyzed quantitative data using regression and qualitative data using immersion/crystallization. RESULTS:One hundred thirty-seven parent-child dyads completed the study (87% Latino, mean child age 9 months). We found differences in the StimQ Reading subscale (B = 0.32; P = .034) and marginal differences in attitudes about reading favoring enhanced ROR. Between-group differences for shared reading frequency, verbal responsivity, and developmental delay were not significant. Qualitative themes provided insight into the enhanced ROR including how it encouraged parents, remaining barriers like competing priorities and lack of social support, and unanticipated benefits (ie, parent appreciation for attention on their families' wellbeing). CONCLUSIONS:A video and text message enhancement to ROR resulted in modest improvements in the home literacy environment over ROR alone. Additional strategies are needed to overcome potent barriers faced by low-income families.

Data addressing prognostication in patients with HIV related Burkitt lymphoma (HIV-BL) currently treated remain scarce. We present an international analysis of 249 (United States: 140; United Kingdom: 109) patients with HIV-BL treated from 2008 to 2019 aiming to identify prognostic factors and outcomes. With a median follow up of 4.5 years, the 3-year progression-free survival (PFS) and overall survival (OS) were 61% (95% confidence interval [CI] 55% to 67%) and 66% (95%CI 59% to 71%), respectively, with similar results in both countries. Patients with baseline central nervous system (CNS) involvement had shorter 3-year PFS (36%) compared to patients without CNS involvement (69%; P < .001) independent of frontline treatment. The incidence of CNS recurrence at 3 years across all treatments was 11% with a higher incidence observed after dose-adjusted infusional etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide (DA-EPOCH) (subdistribution hazard ratio: 2.52; P = .03 vs other regimens) without difference by CD4 count 100/mm3. In multivariate models, factors independently associated with inferior PFS were Eastern Cooperative Oncology Group (ECOG) performance status 2-4 (hazard ratio [HR] 1.87; P = .007), baseline CNS involvement (HR 1.70; P = .023), lactate dehydrogenase >5 upper limit of normal (HR 2.09; P < .001); and >1 extranodal sites (HR 1.58; P = .043). The same variables were significant in multivariate models for OS. Adjusting for these prognostic factors, treatment with cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate, ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) was associated with longer PFS (adjusted HR [aHR] 0.45; P = .005) and OS (aHR 0.44; P = .007). Remarkably, HIV features no longer influence prognosis in contemporaneously treated HIV-BL.

Importance/UNASSIGNED:Obesity disproportionately affects Black women, who also have a higher risk of death after a breast cancer diagnosis compared with women of other racial/ethnic groups. However, few studies have evaluated the association of measures of adiposity with mortality among Black breast cancer survivors. Objective/UNASSIGNED:To assess the association of measures of adiposity with survival after a breast cancer diagnosis among Black women. Design, Setting, and Participants/UNASSIGNED:This prospective population-based cohort study comprised 1891 women with stage 0 to IV breast cancer who self-identified as African American or Black and were ages 20 to 75 years. The New Jersey State Cancer Registry was used to identify women living in 10 counties in New Jersey who were recruited from March 1, 2006, to February 29, 2020, and followed up until September 2, 2020. Exposures/UNASSIGNED:Measures of adiposity, including body mass index, body fat distribution (waist circumference and waist-to-hip ratio), and body composition (percent body fat and fat mass index), were collected during in-person interviews at approximately 10 months after breast cancer diagnosis. Main Outcomes and Measures/UNASSIGNED:All-cause and breast cancer-specific mortality. Results/UNASSIGNED:Among 1891 women, the mean (SD) age at breast cancer diagnosis was 54.5 (10.8) years. During a median follow-up of 5.9 years (range, 0.5-14.8 years), 286 deaths were identified; of those, 175 deaths (61.2%) were associated with breast cancer. A total of 1060 women (56.1%) had obesity, and 1291 women (68.3%) had central obesity. Higher adiposity, particularly higher waist-to-hip ratio, was associated with worse survival. Women in the highest quartile of waist-to-hip ratio had a 61% increased risk of dying from any cause (hazard ratio [HR], 1.61; 95% CI, 1.12-2.33) and a 68% increased risk of breast cancer death (HR, 1.68; 95% CI, 1.04-2.71) compared with women in the lowest quartile. The risks of all-cause and breast cancer-specific death were similarly high among women in the highest quartile for waist circumference (HR, 1.74 [95% CI, 1.26-2.41] and 1.64 [95% CI, 1.08-2.48], respectively), percent body fat (HR, 1.53 [95% CI, 1.09-2.15] and 1.81 [95% CI, 1.17-2.80]), and fat mass index (HR, 1.57 [95% CI, 1.11-2.22] and 1.74 [95% CI, 1.10-2.75]); however, the risk was less substantial for body mass index (HR, 1.26 [95% CI, 0.89-1.79] and 1.33 [95% CI, 0.84-2.10]). In analyses stratified by estrogen receptor status, menopausal status, and age, a higher waist-to-hip ratio was associated with a higher risk of all-cause death among women who had estrogen receptor-negative tumors (HR, 2.24; 95% CI, 1.14-4.41), women who were postmenopausal (HR, 2.15; 95% CI, 1.28-3.61), and women who were 60 years or older at diagnosis (HR per 0.10-U increase, 1.76; 95% CI, 1.37-2.26). Conclusions and Relevance/UNASSIGNED:In this population-based cohort study, central obesity and higher adiposity were associated with higher all-cause and breast cancer-specific mortality among Black breast cancer survivors. Simple measures of body fat distribution and body composition were found to be useful tools for identifying Black women with a higher risk of death after a breast cancer diagnosis.

BACKGROUND:Ultra-processed foods provide 58% of total energy in the U.S. diet, yet their association with cardiovascular disease (CVD) remains understudied. OBJECTIVES/OBJECTIVE:The authors investigated the associations between ultra-processed foods and CVD incidence and mortality in the prospective Framingham Offspring Cohort. METHODS:The analytical sample included 3,003 adults free from CVD with valid dietary data at baseline. Data on diet, measured by food frequency questionnaire, anthropometric measures, and sociodemographic and lifestyle factors were collected quadrennially from 1991 to 2008. Data regarding CVD incidence and mortality were available until 2014 and 2017, respectively. Ultra-processed foods were defined according to the NOVA framework. The authors used Cox proportional hazards models to determine the multivariable association between ultra-processed food intake (energy-adjusted servings per day) and incident hard CVD, hard coronary heart disease (CHD), overall CVD, and CVD mortality. Multivariable models were adjusted for age, sex, education, alcohol consumption, smoking, and physical activity. RESULTS:During follow-up (1991 to 2014/2017), the authors identified 251, 163, and 648 cases of incident hard CVD, hard CHD, and overall CVD, respectively. On average, participants consumed 7.5 servings per day of ultra-processed foods at baseline. Each additional daily serving of ultra-processed foods was associated with a 7% (95% confidence interval [CI]: 1.03 to 1.12), 9% (95% CI: 1.04 to 1.15), 5% (95% CI: 1.02 to 1.08), and 9% (95% CI: 1.02 to 1.16) increase in the risk of hard CVD, hard CHD, overall CVD, and CVD mortality, respectively. CONCLUSIONS:The current findings support that higher consumption of ultra-processed foods is associated with increased risk of CVD incidence and mortality. Although additional research in ethnically diverse populations is warranted, these findings suggest cardiovascular benefits of limiting ultra-processed foods.

Ultraprocessed foods provide the majority of energy content in the American diet, yet little is known regarding consumption trends over time. We determined trends in diet processing level and diet quality from 1991 to 2008 within the prospective Framingham Offspring Cohort. Dietary intakes were collected by FFQ quadrennially 1991-2008 (total of four examinations). The analytical sample included 2893 adults with valid dietary data for ≥3 examinations (baseline mean age = 54 years). Based on the NOVA framework, we classified foods as: unprocessed/minimally processed foods; processed culinary ingredients (salt/sugar/fats/oils); and processed foods and ultraprocessed foods. We evaluated diet quality using the Dietary Guidelines for Americans Adherence Index (DGAI) 2010. Trends in consumption of foods within each processing level (servings/d) and diet quality over the four examinations were evaluated using mixed effects models with subject-specific random intercepts. Analyses were stratified by sex, BMI (<25 kg/m2, 25-29·9 kg/m2, ≥30 kg/m2) and smoking status. Over 17 years of follow-up, ultraprocessed food consumption decreased from 7·5 to 6·0 servings/d and minimally processed food consumption decreased from 11·9 to 11·3 servings/d (Ptrend < 0·001). Changes in intakes of processed foods, culinary ingredients and culinary preparations were minimal. Trends were similar by sex, BMI and smoking status. DGAI-2010 score increased from 60·1 to 61·5, P < 0·001. The current study uniquely describes trends in diet processing level in an ageing US population, highlighting the longstanding presence of ultraprocessed foods in the American diet. Given the poor nutritional quality of ultraprocessed foods, public health efforts should be designed to limit their consumption.