Faculty Bibliography

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine if there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P-values < 5 x 10-8 were considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region which included 45 significantly associated SNPs, was rs1818613 (per allele OR in never smokers 0.87, 95% CI 0.82-0.93; former smokers 1.00, 95 CI 0.91-1.07; current smokers 1.25, 95%CI 1.12-1.40, interaction P-value=3.08x10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high LD with rs1818613 (r2=0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings.

HIV testing rates remain low among youth ages 13-24 in the US, with only 55% of HIV-positive youth aware of their serostatus. We conducted a systematic review to assess the utility of technology-based interventions to increase point-of-care youth HIV testing and linkage to care. We searched PubMed, Embase, CINAHL, and Cochrane CENTRAL for randomized controlled trials of technology-based interventions aimed at increasing point-of-care youth HIV testing, published between 2008 and 2020. All identified citations were independently screened for inclusion by two authors, and the Cochrane Risk of Bias Tool for Randomized Controlled Trials was used to assess the quality of included studies. Three studies met all inclusion criteria. Two interventions were effective in increasing HIV testing, while one was effective at linkage to care. Technology-based interventions have the potential to increase youth HIV testing in clinical settings and facilitate linkage to care, possibly reducing undiagnosed HIV among adolescents and emerging adults.

Wildland fires are diminishing air quality on a seasonal and regional basis, raising concerns about respiratory health risks to the public and occupational groups. This American Thoracic Society (ATS) workshop was convened in 2019 to meet the growing health threat of wildland fire smoke. The workshop brought together a multi-disciplinary group of 19 experts, including wildland fire managers, public health officials, epidemiologists, toxicologists, and pediatric and adult pulmonologists. The workshop examined four major topics: (1) the science of wildland fire incidence and fire management, (2) the respiratory and cardiovascular health effects of wildland fire smoke exposure, (3) communication strategies to address these health risks, and (4) actions to address wildland fire health impacts. Through formal presentations followed by group discussion, workshop participants identified top priorities for fire management, research, communication and public policy to address health risks of wildland fires. The workshop concluded that short-term exposure to wildland smoke causes acute respiratory health effects, especially among those with asthma and chronic obstructive pulmonary disease (COPD). Research is needed to understand long-term health effects of repeated smoke exposures across fire seasons for children, adults and highly exposed occupational groups (especially firefighters). Other research priorities include fire data collection and modeling, toxicology of different fire fuel sources, and the efficacy of health protective measures to prevent respiratory effects of smoke exposure. The workshop committee recommends a unified Federal response to the growing problem of wildland fires, including investment in fire behavior and smoke air quality modeling, research on the health impacts of smoke, and the development of robust clinical and public health communication tools.

Dance festival attendees are at high risk for consuming adulterated drugs. In recent years, drug checking studies have been conducted at various dance festivals to provide valuable harm reduction information to attendees regarding drug content. We conducted a review of the literature to determine the generalizability of findings to the target population of interest-festival attendees at risk for using adulterated drugs. Six published studies involving drug checking at festivals were reviewed. All relied on self-selected samples and male attendees were overrepresented based on previous research. Test methods, drugs tested, definitions of adulteration, and prevalence of adulteration varied across studies. Prevalence of detection of adulterants ranged from 11% to 55%. While the drug checking services described appear to have been beneficial for participants, results have limited generalizability to the target population. We recommend that researchers expand beyond the self-selection model in future studies and utilize recruitment methods that involve random sampling techniques such as systematic random sampling, stratified random sampling, or time-space sampling within festivals. We also recommend that individuals approached are surveyed for demographic characteristics, planned drug use at the festival, and willingness to test their drugs. These methods would help determine how representative the sample is compared to the target population and allow for more generalizable estimates. In conclusion, as these valuable harm reduction services expand, it may be possible to reach a wider portion of the population at risk and to obtain more generalizable estimates of engagement, adulteration, and reactions to learning one possesses adulterated drugs. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The COVID-19 pandemic is a public health crisis, having killed more than 514 000 US adults as of March 2, 2021. COVID-19 mitigation strategies have unintended consequences on managing chronic conditions such as hypertension, a leading cause of cardiovascular disease and health disparities in the United States. During the first wave of the pandemic in the United States, the combination of observed racial/ethnic inequities in COVID-19 deaths and social unrest reinvigorated a national conversation about systemic racism in health care and society. The 4th Annual University of Utah Translational Hypertension Symposium gathered frontline clinicians, researchers, and leaders from diverse backgrounds to discuss the intersection of these 2 critical social and public health phenomena and to highlight preexisting disparities in hypertension treatment and control exacerbated by COVID-19. The discussion underscored environmental and socioeconomic factors that are deeply embedded in US health care and research that impact inequities in hypertension. Structural racism plays a central role at both the health system and individual levels. At the same time, virtual healthcare platforms are being accelerated into widespread use by COVID-19, which may widen the divide in healthcare access across levels of wealth, geography, and education. Blood pressure control rates are declining, especially among communities of color and those without health insurance or access to health care. Hypertension awareness, therapeutic lifestyle changes, and evidence-based pharmacotherapy are essential. There is a need to improve the implementation of community-based interventions and blood pressure self-monitoring, which can help build patient trust and increase healthcare engagement.

PURPOSE/OBJECTIVE:Over half of males experience fertility impairment after childhood cancer therapy, which often causes psychosocial distress. Yet, fertility preservation (FP) remains underutilized. The goals of this study were to determine the feasibility and impact of implementing a family-centered FP values clarification tool on sperm banking attempts among adolescent males newly diagnosed with cancer, and identify key determinants of banking attempts. METHODS:A prospective pilot study was conducted among families of males (12-25 years old), prior to cancer therapy. Thirty-nine of 41 families agreed to participate (95%); 98 participants (32 adolescents, 37 mothers, 29 fathers) completed the Family-centered Adolescent Sperm banking values clarification Tool (FAST). Analyses assessed the impact of the FAST on banking attempts and examined associations between demographic/medical characteristics, FAST subscales (perceived threat, benefits, barriers), and banking attempts. RESULTS:=.59, p=.02) were associated with banking attempts. CONCLUSION/CONCLUSIONS:Adolescent sperm banking attempt rates significantly increased after implementation of a family-centered FP values clarification tool prior to cancer treatment. Findings underscore the importance of targeting both adolescents and their parents, particularly fathers, in FP efforts.

PURPOSE/OBJECTIVE:) modified the effects of FA and creatine supplementation on changes in homocysteine, guanidinoacetate (GAA), total blood arsenic, and urinary arsenic metabolite proportions and indices. METHODS:Study participants (N = 622) received 400 or 800 μg FA, 3 g creatine, 400 μg FA + 3 g creatine, or placebo daily for 12 weeks. RESULTS:Relative to placebo, FA supplementation was associated with greater mean increases in %DMAs among participants with betaine concentrations below the median than those with levels above the median (FDR < 0.05). 400 μg FA/day was associated with a greater decrease in homocysteine among participants with plasma folate concentrations below, compared with those above, the median (FDR < 0.03). Creatine treatment was associated with a significant decrease in %MMAs among participants with choline concentrations below the median (P = 0.04), but not among participants above the median (P = 0.94); this effect did not significantly differ between strata (P = 0.10). CONCLUSIONS:Effects of FA and creatine supplementation on arsenic methylation capacity were greater among individuals with low betaine and choline status, respectively. The efficacy of FA and creatine interventions to facilitate arsenic methylation may be modified by choline and betaine nutritional status. CLINICAL TRIAL REGISTRATION/BACKGROUND:Clinical Trial Registry Identifier: NCT01050556, U.S. National Library of Medicine, https://clinicaltrials.gov ; registered January 15, 2010.

Evidence for Action (E4A), a signature program of the Robert Wood Johnson Foundation, funds investigator-initiated research on the impacts of social programs and policies on population health and health inequities. Across thousands of letters of intent and full proposals E4A has received since 2015, one of the most common methodological challenges faced by applicants is selecting realistic effect sizes to inform calculations of power, sample size, and minimum detectable effect (MDE). E4A prioritizes health studies that are both (1) adequately powered to detect effect sizes that may reasonably be expected for the given intervention and (2) likely to achieve intervention effects sizes that, if demonstrated, correspond to actionable evidence for population health stakeholders. However, little guidance exists to inform the selection of effect sizes for population health research proposals. We draw on examples of five rigorously evaluated population health interventions. These examples illustrate considerations for selecting realistic and actionable effect sizes as inputs to calculations of power, sample size and MDE for research proposals to study population health interventions. We show that plausible effects sizes for population health interventions may be smaller than commonly cited guidelines suggest. Effect sizes achieved with population health interventions depend on the characteristics of the intervention, the target population, and the outcomes studied. Population health impact depends on the proportion of the population receiving the intervention. When adequately powered, even studies of interventions with small effect sizes can offer valuable evidence to inform population health if such interventions can be implemented broadly. Demonstrating the effectiveness of such interventions, however, requires large sample sizes.