Utah Population Research Articles

The Utah Population Database. A Model for Linking Medical and Genealogical Records for Population Health Research

Improving our understanding of the socio-environmental and genetic bases of disease and health outcomes among individuals, families, and populations over time requires extensive longitudinal data on multiple attributes for entire communities, states or nations. This requirement can be difficult to achieve. In this paper we describe a successful example of a database that meets these needs. The Utah Population Database (UPDB) is a unique and powerful database rarely found in the world that has been addressing these data requirements for over 40 years. The UPDB at the University of Utah is one of the world’s richest sources of in-depth information that supports research on genetics, epidemiology, demography, history, and public health. Genetic researchers have used UPDB to identify and study individuals and families that have higher than normal incidence of diseases or other traits, to analyze patterns of genetic inheritance, and to identify specific genetic mutations. Demographers and other social scientists are increasingly using the UPDB to study issues such as trends in fertility transitions and shifts in mortality patterns for both infants and adults. A central component of the UPDB is an extensive set of Utah family histories, in which family members are linked to demographic and medical information. The UPDB includes medical information about cancer, causes of death, and medical details associated with births. It also includes diagnostic records from statewide insurance claims data and healthcare facilities (hospital discharge, ambulatory surgery, emergency department encounters). UPDB is also linked to Medicare claims data, a federal health insurance program generally for persons age 65 or older. The UPDB provides access to information on more than 11 million individuals and supports nearly 400 research projects. We describe in detail the data components of the UPDB, how it can be accessed, issues related to its development, record linkage, governance and privacy protections, as well as plans for future developments.

Population Dynamics and Harvest Management of the Bonneville Cutthroat Trout Fishery in Bear Lake, Idaho–Utah

AbstractLand‐use disturbances and associated losses in habitat quantity and quality negatively affected the Bonneville Cutthroat Trout (BCT) Oncorhynchus clarkii utah population in Bear Lake, Idaho–Utah, in the early 1900s. Bear Lake BCT follow an adfluvial life history strategy, and without access to suitable spawning habitat, the population of wild BCT was nearly extirpated by the early 1950s. In response to this decline, supplementation of the population with hatchery BCT began in 1973. Production of wild BCT was minimal until conservation efforts shifted towards improving fish habitat and access to spawning tributaries. In 2002, only 5% of the population consisted of wild fish; by 2017, nearly 70% of BCT in annual population surveys were wild. As a result, rule changes have been proposed to allow for regulated harvest of wild BCT. However, gaining a comprehensive understanding of the population dynamics of BCT in Bear Lake is critical before changes are made to management of the fishery. The objectives of this study were to describe the population dynamics of wild and hatchery BCT in Bear Lake and evaluate different management options. We evaluated population demographics of hatchery and wild BCT in Bear Lake and used age‐structured population models to assess a variety of management scenarios associated with wild fish harvest regulations (e.g., bag limits). Bonneville Cutthroat Trout grew at relatively fast rates, and females began to mature at age 5. We observed considerable differences in the length and age structure of the hatchery population (i.e., exploited) versus the wild population (i.e., unexploited) of BCT. In general, BCT in Bear Lake were larger and older than Cutthroat Trout O. clarkii in other systems. The current rate of exploitation for hatchery BCT was estimated as 0.27 (i.e., two‐fish daily limit). If the limit were changed to a six‐fish daily limit, the rate of exploitation would be approximately 0.47. A yield‐per‐recruit model evaluating spawning potential ratio indicated that a limit of two wild fish would be a sustainable level of exploitation, whereas a six‐wild‐fish limit would result in recruitment overfishing. This research has provided baseline population dynamics of BCT in Bear Lake that will provide insight for future monitoring efforts. Under current conditions, allowing harvest of either origin BCT in Bear Lake would satisfy angler values while ensuring the persistence of an ecologically and recreationally important population.

PD23-10 PEYRONIE’S DISEASE: A FAMILIAL, HERITABLE CONDITION

You have accessJournal of UrologyCME1 May 2022PD23-10 PEYRONIE’S DISEASE: A FAMILIAL, HERITABLE CONDITION Michael Christensen, Kristy Allen-Brady, and Alexander Pastuszak Michael ChristensenMichael Christensen More articles by this author , Kristy Allen-BradyKristy Allen-Brady More articles by this author , and Alexander PastuszakAlexander Pastuszak More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002565.10AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Peyronie’s Disease (PD) is a superficial fibrosing disorder characterized by inelastic fibrous plaques within the tunica albuginea. Dupuytren’s and Ledderhose disease (DD and LD respectively) are related diseases that affect tissues in the palmar and plantar fascia, respectively. Using a large population database, we previously reported an increased relative risk of disease to relatives of PD probands. We also observed that 75% of PD cases existed within high-risk pedigrees. Both of these findings suggest a genetic component to this disease. Here, we describe the identification of a single high-risk pedigree from which we are identifying genetic variants that may predispose to these disorders. METHODS: The Utah Population Database (UPDB), a resource that includes genealogy information linked to electronic medical records (available since 1995), was used to identify men and their relatives with PD, as well as high risk PD pedigrees. Pedigrees with a significant excess (p<0.05) of observed PD cases among descendants were termed high-risk. For genetic sequencing, individuals from a pedigree demonstrating a high degree of prevalence of PD, DD, and LD were recruited to provide samples from which genomic DNA (gDNA) was extracted. Whole genome sequencing is being conducted on these samples and variants will be evaluated based on variant type, population frequency, role in signaling pathways/gene ontology, co-segregation within the family, and potential impact on protein function. RESULTS: Previous analyses found that 75% of individuals with PD were part of high-risk PD pedigrees. One such high-risk pedigree containing a founder and 19 descendants was identified from our clinic. The founder and two descendants in the pedigree are deceased. Of the living descendants, 9 are male and 8 are female. Twelve of the descendants have responded to survey requests. Of these, 2/6 males report symptoms of PD (33%), 4/12 of the respondents report symptoms of Dupuytren’s Disease (33%), and 3/12 report symptoms of Ledderhose Disease (25%). Saliva samples from respondent individuals have been collected for whole-genome sequencing, which is being initiated. CONCLUSIONS: Most PD cases identified in the UPDB were part of high-risk PD pedigrees, suggesting a familial component to PD, which may extend to other fibrosing disorders. Next-generation sequencing of gDNA from individuals within a high-risk pedigree will determine if genetic variants that may predispose to superficial fibrosing disorders exist within such a pedigree. Source of Funding: Mentored Career Development Award (K08DK115835-01) from the National Institute of Diabetes and Digestive and Kidney Diseases (A.P.) & Sexual Medicine Society of North America Pfizer Research Fellowship in Men’s Health (M.B.C.) © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e413 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Christensen More articles by this author Kristy Allen-Brady More articles by this author Alexander Pastuszak More articles by this author Expand All Advertisement PDF DownloadLoading ...

PD25-12 URBAN FAMILIES AMELIORATE RURAL GENITOURINARY CANCER DISPARITIES

You have accessJournal of UrologyCME1 May 2022PD25-12 URBAN FAMILIES AMELIORATE RURAL GENITOURINARY CANCER DISPARITIES Jeffrey Vehawn, Mouneeb Choudry, Trevor Hunt, Christopher Martin, Jacob Ambrose, Benjamin Haaland, Jonathan Chipman, Heidi A. Hanson, and Brock O'Neil Jeffrey VehawnJeffrey Vehawn More articles by this author , Mouneeb ChoudryMouneeb Choudry More articles by this author , Trevor HuntTrevor Hunt More articles by this author , Christopher MartinChristopher Martin More articles by this author , Jacob AmbroseJacob Ambrose More articles by this author , Benjamin HaalandBenjamin Haaland More articles by this author , Jonathan ChipmanJonathan Chipman More articles by this author , Heidi A. HansonHeidi A. Hanson More articles by this author , and Brock O'NeilBrock O'Neil More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002567.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Previous studies have shown that individuals with cancer who live in rural areas have worse cancer-specific outcomes compared to their urban counterparts. Differences in access to high-quality cancer care and adequate social support may explain some of the observed disparity. Rural patients with relatives in urban areas may have better access to care via an increased ability to navigate the healthcare system than their rural counterparts without relatives in urban areas. In this study, we examine the possibility of a family-based social capital effect on genitourinary cancer survival. We hypothesized that rural patients who have family members living in urban areas have survival outcomes similar to their urban counterparts. METHODS: We performed a retrospective cohort analysis of individuals diagnosed with genitourinary cancers, including prostate, bladder, kidney, penile, and testicular cancers. We constructed familial networks using the Utah Population Database (UPDB). Patients were classified as living in either rural or urban areas based on the rural-urban commuting area (RUCA) codes associated with their zip code of residence at the time of cancer diagnosis. Adult first degree relatives (siblings, parents, children) were identified and classified as urban or rural based on the zip code or county of residence at the time of the patients’ diagnosis or, when unavailable, the county or zip code of residence before or after diagnosis. Overall survival (OS) was analyzed using Cox proportional hazards models. RESULTS: We identified 24,746 individuals diagnosed with genitourinary cancer between 1968-2018. Median follow-up was 8.72 years. After adjusting for sex, age, race, cancer type, health improvement index (HII), and Simpson’s diversity index, urban patients had the best OS at 5 and 10 years (reference group). Rural cancer patients without an urban first degree relative had the worst outcomes with OS hazard ratios at five and ten years of 1.4 (CI 1.23-1.58) and 1.4 (CI 1.26-1.55), respectively. Having an urban first degree relative ameliorated much of the urban-rural disparity with five- and ten-year OS hazard ratios of 1.19 (CI 1.07-1.31) and 1.12 (CI 1.03-1.21), respectively. CONCLUSIONS: Individuals diagnosed with cancer who live in rural areas have worse survival as compared to their urban counterparts, but this relationship appears to be heavily influenced by the presence or absence of relatives who live in urban areas. Further research is needed to better understand the mechanisms through which having an urban family member may contribute to improved cancer outcomes for rural patients. This may help in the crafting of policies that can reduce urban-rural cancer disparities. Source of Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number K08CA234431 and P30CA042014-31S2. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e426 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jeffrey Vehawn More articles by this author Mouneeb Choudry More articles by this author Trevor Hunt More articles by this author Christopher Martin More articles by this author Jacob Ambrose More articles by this author Benjamin Haaland More articles by this author Jonathan Chipman More articles by this author Heidi A. Hanson More articles by this author Brock O'Neil More articles by this author Expand All Advertisement PDF DownloadLoading ...

Population-specific responses of floral volatiles to abiotic factors in changing environments.

Shifts in abiotic factors can affect many plant traits, including floral volatiles. This study examined the response of floral volatiles to water availability and whether phenotypic plasticity to water availability differs among populations. It also investigated genetic differentiation in floral volatiles, determined the effect of temperature on phenotypic plasticity to water availability, and assessed temporal variation in floral scent emission between day and evening, since pollinator visitation differs at those times. Rocky Mountain columbine plants (Aquilegia coerulea), started from seeds collected in three wild populations in Colorado, Utah, and Arizona, were grown under two water treatments in a greenhouse in Madison, Wisconsin, United States. One population was also grown under the two water treatments, at two temperatures. Air samples were collected from enclosed flowers using dynamic headspace methods and floral volatiles were identified and quantified by gas chromatography (GC) with mass spectrometry (MS). Emission of three floral volatiles increased in the wetter environment, indicating phenotypic plasticity. The response of six floral volatiles to water availability differed among populations, suggesting genetic differentiation in phenotypic plasticity. Five floral volatiles varied among populations, and emission of most floral volatiles was greater during the day. Phenotypic plasticity to water availability permits a quick response of floral volatiles in changing environments. The genetic differentiation in phenotypic plasticity suggests that phenotypic plasticity can evolve but complicates predictions of the effects of environmental changes on a plant and its pollinators.

Disease Ecology of a Low-Virulence Mycoplasma ovipneumoniae Strain in a Free-Ranging Desert Bighorn Sheep Population.

Simple SummaryLike many wildlife diseases, bighorn sheep pneumonia can vary in burden. Here, we report on a bighorn sheep pneumonia event that showed much lower symptom and mortality burdens than have been documented previously. We provide detailed descriptions of symptoms, diagnostic testing results, and mixing patterns throughout the population, and end by discussing mechanisms that could have generated the distinct disease ecology associated with this event.Infectious pneumonia associated with the bacterial pathogen Mycoplasma ovipneumoniae is an impediment to bighorn sheep (Ovis canadensis) population recovery throughout western North America, yet the full range of M. ovipneumoniae virulence in bighorn sheep is not well-understood. Here, we present data from an M. ovipneumoniae introduction event in the Zion desert bighorn sheep (Ovis canadensis nelsoni) population in southern Utah. The ensuing disease event exhibited epidemiology distinct from what has been reported elsewhere, with virtually no mortality (0 adult mortalities among 70 animals tracked over 118 animal-years; 1 lamb mortality among 40 lambs tracked through weaning in the two summers following introduction; and lamb:ewe ratios of 34.9:100 in the year immediately after introduction and 49.4:100 in the second year after introduction). Individual-level immune responses were lower than expected, and M. ovipneumoniae appeared to fade out approximately 1.5 to 2 years after introduction. Several mechanisms could explain the limited burden of this M. ovipneumoniae event. First, most work on M. ovipneumoniae has centered on Rocky Mountain bighorn sheep (O. c. candensis), but the Zion bighorns are members of the desert subspecies (O. c. nelsoni). Second, the particular M. ovipneumoniae strain involved comes from a clade of strains associated with weaker demographic responses in other settings. Third, the substructuring of the Zion population may have made this population more resilient to disease invasion and persistence. The limited burden of the disease event on the Zion bighorn population underscores a broader point in wildlife disease ecology: that one size may not fit all events.

Depression and Anxiety Incidence During Pregnancy Between Bariatric Surgery Patients and Matched Control Subjects.

Obesity is a well-known risk factor for depression and mental illnesses. Metabolic and bariatric surgery (MBS) is a common treatment for individuals with severe obesity. Studies suggest that MBS is associated with increased risk of depression. However, little is known if pregnant women following MBS have greater incidence of depression/anxiety than non-surgical pregnant women with severe obesity. Utah Bariatric Surgery Registry (UBSR) was used to identify subjects who underwent bariatric surgery between 1996 and 2016 and were matched (1:2 matching) to subjects with severe obesity from the Utah Population Database (UPDB). Depression and anxiety diagnoses during pregnancy were identified from birth records and electronic medical records (EMRs) during 10months before birth. A multivariate logistic regression with clustering due to same subjects with multiple births was used. Patients included 1427 MBS women (associated 2492 births) and 2854 non-surgical women (associated 4984 births). In the surgical group, 24.4% of the pregnancies had diagnosed depression/anxiety, while 14.3% of the pregnancies in the control group had depression/anxiety (p < 0.01). The surgery group had 1.51 times higher odds of depression and/or anxiety during pregnancy than the control group after controlling for covariates (OR = 1.51, p < 0.01). The present study provides evidence that women who previously underwent MBS have higher odds of depression/anxiety during pregnancy than women with obesity who did not undergo MBS.

Characteristics of Nonelderly Adult Health Care Persistent Super Utilizers in Utah.

In the United States, the top 1% and top 5% of health care spenders account for 23% and 50% of total health care spending, respectively. These high spenders have been coined the term super utilizers (SU). The aim of this study was to identify the characteristics associated with these patients to aid in developing public health interventions aimed at transitioning patients out of the SU category and thus ultimately helping to control health care costs. The authors utilized the Utah All-Payer Claims Database and Utah Population Database from 2013 to 2015 to identify demographics, comorbid conditions, health care utilization, and cost characteristics of persistent super utilizers (PSU) (≥3 hospitalizations per year for 3 years) of health care compared with persistent nonsuper utilizers (PNSU) (<3 hospitalizations per year for 3 years). Multivariable logistic regression was utilized to identify the characteristics associated with PSU versus PNSU. Higher outpatient/Emergency Department/noninpatient (eg, visits with imaging and Centers for Medicare & Medicaid Services preventive visits) health care utilization and spending, and prevalence of comorbid disease and psychosocial conditions were associated with PSU. In multivariable analysis, factors such as heart disease, chronic kidney disease (CKD), diabetes, alcohol abuse, and depression were statistically significantly associated with higher odds of PSU, with the most noteworthy being CKD (odds ratio [OR] 6.85, 95% confidence interval [95% CI] 5.84-8.02; P < 0.001), alcohol abuse (OR 5.90, 95% CI 4.49-7.69; P < 0.001), and heart diseases (OR 4.41, 95% CI 3.74-5.18; P < 0.001). The annual health care cost of a PSU is about 11.5 times greater than a PNSU ($54,776 vs. $4801; P < 0.001).

A Successful Reintroduction of Columbia Spotted Frog (Rana luteiventris) through Repatriation of Recently Hatched Larvae

The Columbia Spotted Frog (Rana luteiventris; CSF) is widely distributed across northwestern North America; however, declines in the southernmost populations, including those in Utah, have resulted in the consideration of this species for protection under the Endangered Species Act. In 1998, a conservation agreement and strategy for Utah's populations of CSF was developed and identified needed conservation actions, including range expansion. We repatriated CSF larvae during 2008–2010 from an extant population in the Provo River into Beaver Creek, a beaver-dominated stream, in the Weber River, a watershed where contemporary surveys indicate CSF have likely been extirpated. In 2011, CSF breeding was first observed in the repatriated population when 11 egg masses were documented in four depositional areas. After ten years of monitoring egg mass numbers, we consider the repatriation a success as this population continues to grow and expand with a high of 54 egg masses (2019) within ten depositional areas (2020). High quality habitat and the large number of CSF larvae transplanted likely attributed to the success of this repatriation. We used 1–2 day old CSF larvae (Gosner life stage 20–21) as the repatriation life stage that we believed would be the most likely to prevent the spread of amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd) from the known chytrid fungus positive donor site in the Provo River. Genetic testing of a robust sample (n = 59) of CSF tadpoles across the repatriation site in 2020 did not detect the presence of Bd, potentially indicating that we did not move Bd through the repatriation. Additional replicates would be required beyond this single experiment, however, to better determine if our transplant techniques are effective at preventing the spread of Bd.

Urban families ameliorate rural genitourinary cancer disparities.

25 Background: Previous studies have shown that individuals with cancer who live in rural areas have worse cancer-specific outcomes compared to their urban counterparts. Differences in access to high-quality cancer care and adequate social support may explain some of the observed disparity. Rural patients with relatives in urban areas may have better access to care via an increased ability to navigate the healthcare system than their rural counterparts without relatives in urban areas. In this study, we examine the possibility of a family-based social capital effect on genitourinary cancer survival. We hypothesized that rural patients who have family members living in urban areas have survival outcomes similar to their urban counterparts. Methods: We performed a retrospective cohort analysis of individuals diagnosed with genitourinary cancers, including prostate, bladder, kidney, penile, and testicular cancers. We constructed familial networks using the Utah Population Database (UPDB). Patients were classified as living in either rural or urban areas based on the rural-urban commuting area (RUCA) codes associated with their zip code of residence at the time of cancer diagnosis. Adult first degree relatives (siblings, parents, children) were identified and classified as urban or rural based on the zip code or county of residence at the time of the patients’ diagnosis or, when unavailable, the county or zip code of residence before or after diagnosis. Overall survival (OS) was analyzed using Cox proportional hazards models. Results: We identified 24,746 individuals diagnosed with genitourinary cancer between 1968-2018. Median follow-up was 8.72 years. After adjusting for sex, age, race, cancer type, health improvement index (HII), and Simpson’s diversity index, urban patients had the best OS at 5 and 10 years (reference group). Rural cancer patients without an urban first degree relative had the worst outcomes with OS hazard ratios at five and ten years of 1.4 (CI 1.23-1.58) and 1.4 (CI 1.26-1.55), respectively. Having an urban first degree relative ameliorated much of the urban-rural disparity with five- and ten-year OS hazard ratios of 1.19 (CI 1.07-1.31) and 1.12 (CI 1.03-1.21), respectively. Conclusions: Individuals diagnosed with cancer who live in rural areas have worse survival as compared to their urban counterparts, but this relationship appears to be heavily influenced by the presence or absence of relatives who live in urban areas. Further research is needed to better understand the mechanisms through which having an urban family member may contribute to improved cancer outcomes for rural patients. This may help in the crafting of policies that can reduce urban-rural cancer disparities. Funding: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health (K08CA234431 &amp; P30CA042014-31S2). The content does not represent the views of the National Institutes of Health.

External validation of a mobile clinical decision support system for diarrhea etiology prediction in children: A multicenter study in Bangladesh and Mali

Diarrheal illness is a leading cause of antibiotic use for children in low- and middle-income countries. Determination of diarrhea etiology at the point-of-care without reliance on laboratory testing has the potential to reduce inappropriate antibiotic use. This prospective observational study aimed to develop and externally validate the accuracy of a mobile software application ('App') for the prediction of viral-only etiology of acute diarrhea in children 0-59 months in Bangladesh and Mali. The App used a previously derived and internally validated model consisting of patient-specific ('present patient') clinical variables (age, blood in stool, vomiting, breastfeeding status, and mid-upper arm circumference) as well as location-specific viral diarrhea seasonality curves. The performance of additional models using the 'present patient' data combined with other external data sources including location-specific climate, data, recent patient data, and historical population-based prevalence were also evaluated in secondary analysis. Diarrhea etiology was determined with TaqMan Array Card using episode-specific attributable fraction (AFe) >0.5. Of 302 children with acute diarrhea enrolled, 199 had etiologies above the AFe threshold. Viral-only pathogens were detected in 22% of patients in Mali and 63% in Bangladesh. Rotavirus was the most common pathogen detected (16% Mali; 60% Bangladesh). The present patient+ viral seasonality model had an AUC of 0.754 (0.665-0.843) for the sites combined, with calibration-in-the-large α = -0.393 (-0.455--0.331) and calibration slope β = 1.287 (1.207-1.367). By site, the present patient+ recent patient model performed best in Mali with an AUC of 0.783 (0.705-0.86); the present patient+ viral seasonality model performed best in Bangladesh with AUC 0.710 (0.595-0.825). The App accurately identified children with high likelihood of viral-only diarrhea etiology. Further studies to evaluate the App's potential use in diagnostic and antimicrobial stewardship are underway. Funding for this study was provided through grants from the Bill and Melinda GatesFoundation (OPP1198876) and the National Institute of Allergy and Infectious Diseases (R01AI135114). Several investigators were also partially supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116163). This investigation was also supported by the University of Utah Population Health Research (PHR) Foundation, with funding in part from the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002538. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the study design, data collection, data analysis, interpretation of data, or in the writing or decision to submit the manuscript for publication.

Early life adversity, reproductive history and breast cancer risk.

Background and objectivesIndividuals who experience early life adversity are at an increased risk for chronic disease later in life. Less is known about how early life factors are associated with cancer susceptibility. Here, we use a life history framework to test whether early life adversity increases the risk of breast cancer. We predict that early life adversity can shift investment in somatic maintenance and accelerate the timing of reproduction, which may mediate or interact with the risk of breast cancer.MethodologyWe use population-wide data from the Utah Population Database (UPDB) and Utah Cancer Registry, leading to 24 957 cases of women diagnosed with breast cancer spanning 20 years (1990–2010) and 124 785 age-matched controls. We generated a cumulative early life adversity summation score to evaluate the interaction (moderation) and mediation between early life adversity, reproductive history and their association with breast cancer risk.ResultsOur analyses led to three key findings: (i) more early life adversity, when considered as a main effect, accelerates the time to first birth and death, (ii) early age at first birth and high parity decreases the risk of breast cancer and (iii) we find no association between early adversity and breast cancer risk either as a main effect or in its interaction with reproductive history.Conclusion and implicationsEarly adversity elevates the risk of overall mortality through mechanisms other than breast cancer risk. This suggests early life factors can generate different effects on health. Future work should incorporate more complex view of life history patterns, including multiple life stages, when making predictions about cancer susceptibility.

Association of Non-Melanoma Skin Carcinomas and UV Exposure with Exfoliation Syndrome in Utah

Background: Prior data suggest an association between non-melanoma skin cancer, i.e., basal and squamous cell cancers most often located in areas of sun exposure, and pseudoexfoliation syndrome. This study aimed to evaluate the association between these conditions and UV exposure through a detailed questionnaire in a large and robust Utah population. Methods: The two arms of this study are a population-based study (evaluated via chart review) and a UV exposure study (evaluated via a questionnaire). Participants answered a questionnaire designed to assess lifelong UV exposure, including leisure and occupational sun exposure, likelihood to tan or burn in early life, eye and hair color, smoking behavior, vitamin D deficiency, skin cancer history, alcohol consumption, and caffeine intake. Conclusion: Descriptive findings suggest UV exposure over an adult’s lifespan may associate with a higher risk of non-melanoma skin cancer in Utah exfoliation patients vs. unaffected individuals. Patients with exfoliation glaucoma reside at higher elevations than non-glaucoma patients.

Hypertensive disorders of pregnancy and risk of Alzheimer’s disease, vascular dementia, and other related dementia

Several recent studies have examined whether hypertensive disorders of pregnancy (HDP) are associated with an increased risk for Alzheimer’s disease (AD) and other related dementias (RD) with conflicting findings. Limitations to prior studies include lack of assessing risk by dementia subtype, inadequate sample sizes, and not fully exploring the role of mid-life factors. We performed a retrospective matched cohort study among women with >1 singleton pregnancy (1939–2013) using the Utah Population Database. HDP-exposed women (n=19,989) were one-to-two matched with unexposed women (n=39,679) by 5-year age groups, year of childbirth (within 1 year), and parity (1, 2, 3, 4, ≥5) at the time of the pregnancy. HDP pregnancies were complicated by preeclampsia (62%), gestational hypertension (34%), and eclampsia (4%). Women with a history of HDP had a higher hazard of all-cause dementia (HR=1.37; 95% CI: 1.26, 1.50) compared to women without a history of HDP after adjustment for maternal age, year of childbirth, and parity. The hazard doubled after additionally accounting for pre-pregnancy BMI (HR=2.31; 95% CI: 1.24, 4.32). Stratifying by dementia subtype, we found HDP to be associated with a higher hazard of vascular dementia (HR=1.64; 95% CI: 1.19, 2.26) and other related dementia (HR=1.49; 95% CI: 1.34, 1.65) but not Alzheimer’s disease (HR=1.04; 95% CI: 0.87, 1.24) after accounting for competing risks. Mid-life hypertension and stroke were found to have the greatest mid-life impact, mediating 43% and 41% of dementia risk, respectively, highlighting women who may most benefit from close surveillance and early preventive and clinical interventions.

Age-Related Disease Risks in Younger versus Older B-Cell Non-Hodgkin's Lymphoma Survivors.

Younger cancer survivors may develop age-related diseases due to the cancer treatment that they undergo. The aim of this population-based study is to estimate incidence of age-related diseases besides cardiovascular disease among younger versus older B-cell non-Hodgkin's lymphoma (B-NHL) survivors compared with their respective general population cohorts. Survivors of B-NHL were diagnosed between 1997 and 2015 from the Utah Cancer Registry. Using the Utah Population Database, up to 5 cancer-free individuals from the general population were matched with a B-NHL survivor on sex, birth year, and state of birth. Hazard ratios (HR) for age-related disease outcomes, which were identified from medical records and statewide health care facility data, were estimated using Cox Proportional Hazards models for B-NHL survivors diagnosed at <65 years versus ≥65 years at least 5 years since B-NHL diagnosis. Comparing 2,129 B-NHL survivors with 8,969 individuals from the general population, younger B-NHL survivors had higher relative risks of acute renal failure [HR, 2.24; 99% confidence interval (CI), 1.48-3.39; P heterogeneity = 0.017), pneumonia (HR, 2.42; 99% CI, 1.68-3.49; P heterogeneity = 0.055), and nutritional deficiencies (HR, 2.08; 99% CI, 1.48-2.92; P heterogeneity = 0.051) ≥5 years after cancer diagnosis. Younger B-NHL survivors had higher relative risks of acute renal failure, pneumonia, and nutritional deficiencies than older B-NHL survivors compared with their respective general population cohorts, ≥5 years after cancer diagnosis.

Protocol for #iBeatCRC: a community-based intervention to increase early-onset colorectal cancer awareness using a sequential explanatory mixed-methods approach

IntroductionThe last two decades have seen a twofold increase in colorectal cancer (CRC) incidence among individuals under the recommended screening age of 50 years. Although the origin of this early-onset...

Lower female partner live birth rate in male cancer survivors: An age-matched cohort analysis of the Utah Population Database.

We determine the time to first live birth for female partners of males after a cancer diagnosis. Our group performed a retrospective, population-based, age-matched cohort study of Utah male residents diagnosed with cancer at age 18years or later between 1956 and 2013 (exposed) matched to male Utah residents without cancer diagnosis (unexposed). Using stratified Cox proportional hazard models, we adjusted for race, ethnicity and number of live births prior to cancer diagnosis, to estimate the effect of time to a partner live birth following cancer diagnosis. Our study cohort included 19,303men diagnosed with cancer (exposed) and 93,608 age-matched men without cancer diagnoses (unexposed). Exposed men were less likely to have a live birth prior to first cancer diagnosis (60.7% vs. 65.4%, p<0.001) and after first cancer diagnosis (10.9% vs. 12.2%, p<0.001) compared to unexposed men. Exposed men had a fertility hazard rate that was 31% lower after cancer diagnosis date than unexposed men (HR: 0.69; 95% CI: 0.65-0.72). This was most profound for men aged 18-30years (HR: 0.59, 95% CI: 0.55-0.63). Male cancer survivors have a 31% lower female partner live birth rate after cancer diagnosis. These findings are important for patient counselling regarding fertility preservation at the time of cancer diagnosis.

Cystic Fibrosis Increases Long-Term Revision Rates of Endoscopic Sinus Surgery in Patients With Comorbid Chronic Rhinosinusitis.

Background: Comorbid chronic rhinosinusitis (CRS) of adulthood is increasing among patients with cystic fibrosis (CF) due to improved median survival. However, little is known about the natural history of endoscopic sinus surgery (ESS) in this cohort. The objective of this study was to evaluate the revision rate of ESS and associated risk factors among adults with CRS and CF (CRSwCF). Methods: The Utah Population Database was queried for patients age >18 with CRS who underwent at least one ESS between 1996 and 2018. Demographic information and ESS history were collected and compared for CRSwCF versus CRS without CF (CRSsCF) using chi-square and t-tests. Risk factors for revision were analyzed using Cox proportional hazard models and logistic regression analysis. Results: A total of 34050 patients (33639 CRSsCF and 411 CRSwCF) were included in the final analysis. The mean duration of follow-up was 9.3 and 9.3 years, respectively (P = .98). Adult patients with CF were significantly more likely to undergo revision ESS (18.7%) than those without CF (13.4%; P < .01). Logistic regression analysis indicated that a diagnosis of CF independently elevated the risk for revision ESS in the absence of nasal polyps (odds ratio [OR] 2.18, confidence interval [CI] 1.34-3.54), asthma (OR 1.36, CI 0.94-1.98), and allergies (OR 1.29, CI 0.90-1.73). Conclusion: In the era before highly effective modulator therapies, the mean revision rate of ESS among adults with CRSwCF was 18.7%, significantly greater than that of adults with CRSsCF. CF was an independent risk factor for revision ESS in the absence of nasal polyps, asthma, and allergies.

44.6 Clinical and Genetic Evaluation of Suicide Death Among Young Individuals Exposed to Trauma

Suicide is the second leading cause of death in the United States for individuals aged 10 to 24 years and remains difficult to predict despite being inherently preventable. Exposure to trauma is known to be a risk factor for suicidal behavior and worse mental health clinical trajectories. This study leverages a unique collection of individuals who have died from suicide as part of the Utah Population Database (UPDB) to evaluate clinical and genetic risk factors for death by suicide in young individuals (aged 12-25 years) who have a history of exposure to trauma. A total of 9052 UPDB deidentified individuals who died from suicide and had linked medical records were evaluated. Individuals aged 0 to 25 years with a diagnosis of PTSD or medically documented trauma were selected (N = 156; “YTS”). YTS were compared with remaining individuals who died by suicide (N = 8,869; “AS”) by common comorbid diagnoses (found in ≥5% of all subjects). Significant findings were used to direct a polygenic risk score (PRS) assessment of a subset of genotyped European individuals (YTS N = 85; AS N = 3766). All statistics utilized logistic regression and were adjusted for critical covariates and multiple tests. Clinical analyses yielded several diagnoses that were overrepresented within the YTS group as compared with the AS group. These included MDD (OR = 4.7; 95% CI, 3.1-7.2), generalized anxiety disorder (OR = 3.4; 95% CI, 2.0-5.6), bipolar disorder (OR = 3.0; 95% CI, 1.8-5.0), tobacco use disorder (OR = 2.9; 95% CI, 1.8-4.4), and unspecified psychosis (OR = 2.6; 95% CI, 1.4-4.7). PRSs were calculated based on large studies of anxiety, PTSD, MDD, bipolar disorder, and smoking, but none survived correction, noting nominal significance of PTSD PRSs. These results identify several comorbid diagnoses that may serve as combined risk factors for suicide death in the setting of young, trauma-exposed individuals, as compared with other suicide deaths. A particular enrichment of major mental health diagnoses and substance use was observed. These findings may be helpful in directing future screening and research efforts targeted toward identifying those at highest risk for suicide.

Risk of atrial fibrillation is increased in patients with exfoliation syndrome: the Utah project on exfoliation syndrome (UPEXS).

Exfoliation syndrome, a systemic disorder with ocular manifestations, is associated with lysyl oxidase-like gene variants. Along with transforming growth factor beta-1, lysyl oxidase-like 1 is a key enzyme in stabilizing extracellular matrix and remodelling collagen/elastin. Given the role that transforming growth factor beta-1, lysyl oxidase-like gene variants and fibrosis play in atrial fibrillation, an association with exfoliation syndrome was investigated. An exfoliation syndrome cohort of 2803 patients and an atrial fibrillation cohort of 43 694 patients aged 60-90 years at disease onset were identified using the Utah Population Database (1996-2015). Conditional logistic regression was used to estimate risk of atrial fibrillation in exfoliation syndrome patients and risk of exfoliation syndrome in atrial fibrillation patients compared with respective 5:1 sex- and age-matched control cohorts. Kaplan-Meier curves were examined to assess survival in atrial fibrillation patients by exfoliation syndrome status. Exfoliation syndrome patients had a 21% greater risk (95% CI 1.06-1.37; p < 0.0001) of atrial fibrillation. This was more pronounced in exfoliation syndrome patients with no hypertension history, who exhibited a 52% increased atrial fibrillation risk (95% CI 1.27-1.82; p < 0.0001). Atrial fibrillation patients exhibited a 20% increased risk of exfoliation syndrome (95% CI 1.07-1.35; p = 0.003), while atrial fibrillation patients with no hypertension had a 72% higher exfoliation risk (95% CI 1.45-2.03; p < 0.0001). Atrial fibrillation patients with exfoliation syndrome had a higher estimated probability of survival (alive at study end or at last follow-up) compared with patients with no exfoliation history (p < 0.0001, log-rank test). Exfoliation syndrome patients were at a statistically significant increased risk of atrial fibrillation. Similarly, atrial fibrillation patients were at a statistically significant higher risk of exfoliation, particularly when hypertension history was absent.