Faculty Bibliography

BACKGROUND:Associations of arsenic (As) with the sum of 5-mC and 5-hmC levels have been reported; however, As exposure-related differences of the separated 5-mC and 5-hmC markers have rarely been studied. METHODS:In this study, we evaluated the association of arsenic exposure biomarkers and 5-mC and 5-hmC in 30 healthy men (43-55 years) from the Aragon Workers Health Study (AWHS) (Spain) and 31 healthy men (31-50 years) from the Folic Acid and Creatinine Trial (FACT) (Bangladesh). We conducted 5-mC and 5-hmC profiling using Infinium MethylationEPIC arrays, on paired standard and modified (ox-BS in AWHS and TAB in FACT) bisulfite converted blood DNA samples. RESULTS:The median for the sum of urine inorganic and methylated As species (ΣAs) (μg/L) was 12.5 for AWHS and 89.6 for FACT. The median of blood As (μg/L) was 8.8 for AWHS and 10.2 for FACT. At a statistical significance p-value cut-off of 0.01, the differentially methylated (DMP) and hydroxymethylated (DHP) positions were mostly located in different genomic sites. Several DMPs and DHPs were consistently found in AWHS and FACT both for urine ΣAs and blood models, being of special interest those attributed to the DIP2C gene. Three DMPs (annotated to CLEC12A) for AWHS and one DHP (annotated to NPLOC4) for FACT remained statistically significant after false discovery rate (FDR) correction. Pathways related to chronic diseases including cardiovascular, cancer and neurological were enriched. CONCLUSIONS:While we identified common 5-hmC and 5-mC signatures in two populations exposed to varying levels of inorganic As, differences in As-related epigenetic sites across the study populations may additionally reflect low and high As-specific associations. This work contributes a deeper understanding of potential epigenetic dysregulations of As. However, further research is needed to confirm biological consequences associated with DIP2C epigenetic regulation and to investigate the role of 5-hmC and 5-mC separately in As-induced health disorders at different exposure levels.

Efforts to engage adolescent girls and young women (AGYW) in HIV services have struggled, in part, due to limited awareness of services and stigma. Strategic marketing is a promising approach, but the impact on youth behavior change is unclear. We report findings from a mixed methods evaluation of the Girl Champ campaign, designed to generate demand for sexual and reproductive services among AGYW, and piloted in three clinics in the Manzini region of eSwatini. We analyzed and integrated data from longitudinal, clinic-level databases on health service utilization among AGYW before and after the pilot, qualitative interviews with stakeholders responsible for the implementation of the pilot, and participant feedback surveys from attendees of Girl Champ events. Girl Champ was well received by most stakeholders based on event attendance and participant feedback, and associated with longitudinal improvements in demand for HIV services. Findings can inform future HIV demand creation interventions for youth.

The use of planned oocyte cryopreservation for nonmedical need has been steadily increasing, especially since the experimental label on this procedure was lifted nearly 10 years ago. With this rise, patients' desires to postpone or conserve their reproductive potential have become increasingly nuanced, and the need for complex individualized counseling has grown. In addition, there are several ethical considerations, including risks, access, and patient comprehension that must be discussed with patients who are considering this procedure. In this review, we provide an in-depth discussion of these concepts, highlighting the need for individualized and comprehensive counseling that recognizes the gaps in knowledge that remains in this somewhat novel domain.

INTRODUCTION:Optimism is associated with better cardiovascular health, yet little is known about the underlying mechanisms and whether protective relationships are consistently observed across diverse groups. This study examines optimism's association with lipid profiles over time and separately among Black and White men and women. METHODS:Data were from 3,206 middle-aged adults in the Coronary Artery Risk Development in Young Adults study. Optimism was measured in 2000-2001 using the Revised Life Orientation Test. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol measurements were obtained at 5-year intervals through 2015-2016. Linear mixed models evaluated relationships between optimism and lipids, adjusting for covariates, including prebaseline lipids. Subgroup differences were examined using interaction terms and stratification. All analyses were conducted in 2020. RESULTS:Higher optimism was associated with both lower baseline total cholesterol (β= -2.33, 95% CI= -4.31, -0.36) and low-density lipoprotein cholesterol levels (β= -1.93, 95% CI= -3.65, -0.21) and a more rapid incremental increase in both markers over time (total cholesterol: β=0.09, 95% CI=0.00, 0.18; low-density lipoprotein cholesterol: β=0.09, 95% CI=0.01, 0.16). No associations were apparent with baseline triglycerides, high-density lipoprotein cholesterol, or changes in either lipid over time. Tests for interaction only found evidence of heterogeneous associations with baseline triglyceride levels, but stratified models hinted at stronger protective associations with baseline levels of total cholesterol and low-density lipoprotein cholesterol among White women. CONCLUSIONS:Optimism may help diverse individuals establish healthy total cholesterol and low-density lipoprotein cholesterol levels before midlife. Although associations were largely consistent across subgroups, stronger associations among White men and White women highlight a need to study optimism's health impact in diverse samples.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Novel aptamer-based technologies can identify >7000 analytes per sample, offering a high-throughput alternative to traditional immunoassays in biomarker discovery. However, the specificity for distinct proteins has not been thoroughly studied in the context of CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:We assessed the use of SOMAscan, an aptamer-based technology, for the quantification of eight immune activation biomarkers and cystatin C among 498 African American Study of Kidney Disease and Hypertension (AASK) participants using immunoassays as the gold standard. We evaluated correlations of serum proteins as measured by SOMAscan versus immunoassays with each other and with iothalamate-measured GFR. We then compared associations between proteins measurement with risks of incident kidney failure and all-cause mortality. RESULTS:both methods. On average, immunoassay measurements were more strongly associated with adverse outcomes than their SOMAscan counterparts. CONCLUSIONS:SOMAscan is an efficient and relatively reliable technique for quantifying IL-8, TNFRSF1B, cystatin C, and TNFRSF1A in CKD and detecting their potential associations with clinical outcomes.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_23_CJN11700921.mp3.

OBJECTIVE:Skilled nursing facilities (SNFs) are common destinations after hospitalization for patients with heart failure (HF). Our objective was to determine if patients in SNFs with a primary hospital discharge diagnosis of HF benefit from an HF disease management program (HF-DMP). DESIGN/METHODS:This is a subgroup analysis of multisite, physician and practice blocked, cluster-randomized controlled trial of HF-DMP vs usual care for patients in SNF with an HF diagnosis. The HF-DMP standardized SNF HF care using HF practice guidelines and performance measures and was delivered by an HF nurse advocate. SETTING AND PARTICIPANTS/METHODS:Patients with a primary hospital discharge diagnosis of HF discharged to SNF. METHODS:Composite outcome of all-cause hospitalization, emergency department visits, and mortality were evaluated at 30 and 60 days post SNF admission. Linear mixed models accounted for patient clustering at the physician level. RESULTS:Of 671 individuals enrolled in the main study, 125 had a primary hospital discharge diagnosis of HF (50 HF-DMP; 75 usual care). Mean age was 79 ± 10 years, 53% women, and mean ejection fraction 46% ± 15%. At 60 days post SNF admission, the rate of the composite outcome was lower in the HF-DMP group (30%) compared with usual care (52%) (P = .02). The rate of the composite outcome at 30 days for the HF-DMP group was 18% vs 31% in the usual care group (P = .11). CONCLUSIONS AND IMPLICATIONS/CONCLUSIONS:Patients with a primary hospital discharge diagnosis of HF who received HF-DMP while cared for in an SNF had lower rates of the composite outcome at 60 days. Standardized HF management during SNF stays may be important for patients with a primary discharge diagnosis of HF.

RATIONALE & OBJECTIVE/OBJECTIVE:The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN/METHODS:Observational study. SETTING & PARTICIPANTS/METHODS:We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease. EXPOSURE/METHODS:Estimated glomerular filtration rate (eGFR). OUTCOME/RESULTS:NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH/METHODS:We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS:decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]). LIMITATIONS/CONCLUSIONS:Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting. CONCLUSIONS:In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.

PURPOSE/OBJECTIVE:Black men have the highest incidence and mortality from prostate cancer (PCa) and lower quality of life compared to other U.S. racial groups. Additionally, more Latinx men are diagnosed with advanced disease and fewer receive guideline-concordant care. As many men seek medical information online, high-quality information targeting diverse populations may mitigate disparities. We examined racial/ethnic representation and information quality in online PCa content. MATERIALS AND METHODS/METHODS:We retrieved 150 websites and 150 videos about "prostate cancer" using the most widely used search engine (Google) and social network (YouTube). We assessed quality of health information, reading level, perceived race/ethnicity of people featured in the content and discussion of racial/ethnic disparities. RESULTS:Among 81 websites and 127 videos featuring people, 37% and 24% had perceived Black representation, and racial/ethnic disparities were discussed in 27% and 17%, respectively. Among 1,526 people featured, 9% and 1% were perceived as Black and Latinx, respectively. No content with Black or Latinx representation was high quality, understandable, actionable and at the recommended reading level. CONCLUSIONS:Black and Latinx adults are underrepresented in online PCa content. Online media have significant potential for public education and combating health disparities. However, most PCa content lacks diversity and is not readily understandable.

Low-income adults are significantly more likely to smoke, and face more difficulty in quitting, than people with high income. High rates of delay discounting (DD) may be an important factor contributing to the high rates of tobacco use among low-income adults. Future-oriented financial coaching may offer a novel approach in the treatment of smoking cessation among low-income adults. This secondary analysis (N = 251) of data from a randomized controlled trial examined the integration of future-oriented financial coaching into smoking cessation treatment for low-income smokers. Linear regression and finite mixture models (FMM) estimated the overall and the latent heterogeneity of the impact of the intervention versus usual care control on DD rates 6 months after randomization. Though standard linear regression found no overall difference in DD between intervention and control (β = -0.23, p = 0.338), the FMM identified two latent subgroups with different responses to the intervention. Subgroup 1 (79% of the sample) showed no difference in DD between intervention and control (β = 0.25, p = 0.08). Subgroup 2 (21% of the sample) showed significantly lower DD (β = -2.06, p = 0.003) among intervention group participants versus control at 6 months. Participants were more likely to be a member of subgroup 2 if they had lower baseline DD rates, were living at or below 100% of federal poverty, or were married/living with a partner. This study identified a group of low-income adults seeking to quit smoking who responded to financial coaching with decreased DD rates. These results can be used to inform future targeting of the intervention to individuals who may benefit most, as well as inform future treatment adaptations to support the subgroup of low-income smokers, who did not benefit.

BACKGROUND:The coronavirus pandemic (COVID-19) has placed strains on communities. In the midst of this public health crisis, health systems have created remote methods of monitoring symptom progression and delivering care virtually. OBJECTIVE:Using a text message-based system, we sought to build and test a remote model to explore community needs, connect individuals to curated resources, and facilitate community health worker intervention when needed during COVID-19. The primary aims of this pilot study were to establish the feasibility (i.e., engagement with the text line) and acceptability (i.e., participant ratings of resources and service) of delivering automated wellbeing resources via smartphone technology. METHODS:Eligible patients (18 years or older, cell phone with SMS capability, and recent ED visit) were identified using the EHR. Patients were consented to enroll and begin receiving COVID-19 related information and links to community resources. We collected open- and close-ended resource and mood ratings. We calculated the frequencies and conducted thematic review of open-ended responses. RESULTS:In seven weeks, 356 participants were enrolled; 13,917 messages were exchanged including 333 resource ratings (mean 4) and 673 well-being scores (mean 6.8). We received and coded 386 open-ended responses, most elaborated upon their self-reported mood score (29%). Overall, 77% of our participants rated the platform as a service they would highly recommend to a family member or friend. CONCLUSIONS:This approach is designed to broaden the reach of health systems, tailor to community needs in real-time, and connect at-risk individuals with robust community health support. CLINICALTRIAL/UNASSIGNED/: