Utah Population Research Articles

The Secondary Sex Ratio and Male Mortality at Pre-Reproductive Ages: A Test of Selection In Utero.

The secondary sex ratio (i.e., the ratio of male to female live births; hereafter referred to as the SSR) falls in populations encountering ambient stressors. Much theory and some empirical work indicates that males born to low SSR cohorts may be "positively selected" in that excess culling in utero may correspond with greater than expected survival among live-born males in that cohort. We extend prior work by testing, in historical Utah, whether the SSR varies positively with male mortality at pre-reproductive ages. This study uses detailed records from the Utah Population Database to focus on Utahns born 1850-1940. We use rigorous time-series methods, which control for strong secular declines in mortality as well as ambient perturbations shared equally among males and females, to investigate the male culling inference. We observe a positive relation between the SSR and male mortality during youth (i.e., 5 to < 20 years; p < 0.05) but not in infancy or early childhood. In this historical population, the SSR appears to gauge hardiness of surviving male cohorts. However, whether the high fertility and/or family structure context of Latter-day Saints in historical Utah explains the age-specific pattern of male mortality warrants further scrutiny.

7326 Breast and Ovarian Cancer are Increased in Women with Primary Ovarian Insufficiency and Early Menopause and Cancer is Increased in Family Members

Abstract Disclosure: K.L. Allen-Brady: None. L. Verrilli: None. M. Alvord: None. M. Kern: None. N. Camp: None. K. Kelley: Consulting Fee; Self; Immunogen. J. Letourneau: None. L. Cannon-Albright: None. E.B. Johnstone: Stock Owner; Self; Abbott Laboratories, Abbvie. C.K. Welt: None. Introduction: Next generation sequencing in women with primary ovarian insufficiency (POI) identified deleterious variants in DNA damage repair and transcription fidelity genes. Based on underlying genetics, we hypothesized that a subset of women with POI may also be predisposed to reproductive or hormonally influenced cancers and that family members may be at risk. Methods: Women with POI (≤40 years) and early menopause &amp;gt;40 and &amp;lt;45 years) were identified using ICD9 and 10 codes in electronic medical records (1995-2021) from two major healthcare systems in Utah and reviewed for accuracy. Women with POI and their relatives were linked to genealogy information using the Utah Population Database (UPDB) and to cancer diagnoses (breast, ovarian, endometrial, colon, testicular and prostate) using the Utah Cancer Registry. The relative risk (RR) of cancer in women with POI and in relatives was estimated by comparison to population rates matched by age, sex, and birthplace. We also identified POI pedigrees with an excess number of observed cancer cases compared to the expected number in population controls. Results: We identified 613 women with POI and 165 women with early menopause. Of these, 416 women with POI had at least three generations of genealogical data with 2,405 first-degree relatives, 6,798 second-degree relatives and 17,666 third-degree relatives. Breast cancer was significantly increased in women with POI (OR [95%CI] 1.89 [1.20, 2.84]; p=0.0056) and there was a borderline increase in ovarian cancer. Probands were 36.5±4.3 years when diagnosed with POI and 59.5±12.7 years (range 43-80 years) at the time of breast cancer diagnosis and only 2 women took hormone replacement therapy after age 50 years. When women with early menopause were added, breast cancer risk remained increased and ovarian cancer was also nominally significant (3.38 [1.15, 8.65]; p=0.032). There was no increased risk of endometrial cancer and there were no cases of colon cancer. Among second-degree relatives of women with POI and 3 generations of family members, there was a significantly increased risk of breast (1.28 [1.08, 1.71]; p=0.0078) and colon cancer (1.50 [1.14, 1.94]; p=0.0036). Prostate cancer was increased in first- (1.64 [1.18, 2.23]; p=0.0026), second- (1.54 [1.32, 1.79]; p&amp;lt;0.001), and third-degree relatives (1.33 [1.20, 1.48]; p&amp;lt;0.001). There were 27 POI pedigrees that were high risk for these reproductive or hormonally influenced cancer diagnoses. Conclusions: Our data suggest common risk factors for POI and reproductive or hormonally influenced cancers. Therefore, clinicians need tools to predict cancer risk and comorbid disease in women with POI and early menopause to adequately counsel about future health risk. This understanding may change recommendations for hormone replacement based on the underlying genetic cause of POI for an individual. Presentation: 6/3/2024

Imperiled wanderlust lichens in steppe habitats of western North America comprise geographically structured mycobiont lineages and a reversal to sexual reproduction within this asexual clade

The northern North American Cordillera is a globally significant center of endemism. In western North America, imperiled arid steppe habitats support a number of unique species, including several endemic lichens. However, processes driving diversification and endemism in this region remain unclear. In this study, we investigate diversity and phylogeography of the threatened wanderlust lichens (mycobiont = Rhizoplaca species) which occur unattached on calcareous soils in steppe habitats in western North America. Wanderlust lichens comprise three species of lichen-forming fungi (LFF) – Rhizoplaca arbuscula, R. haydenii, and R. idahoensis (endangered, IUCN Red List) – which occur in fragmented populations in Idaho and Wyoming, with more limited populations in southeastern Montana and northern Utah. These lichens reproduce almost exclusively via large, asexual vegetative propagules. Here, our aims were to (i) assess the evolutionary origin of this group and identify phylogeographic structure, (ii) infer ancestral geographic distributions for lineages within this clade, and (iii) use species distribution modeling to better understand the distribution of contemporary populations. Using a genome-skimming approach, we generated a 19.1 Mb alignment, spanning ca. half of the complete LFF genome, from specimens collected throughout the entire range of wanderlust lichens. Based on this phylogeny we investigated phylogeographic patterns using RASP. Finally, we used MaxEnt to estimate species distribution models for R. arbuscula and R. haydenii. We inferred a highly structured topology, with clades corresponding to distinct geographic regions and morphologies represented throughout the group’s distribution. We found that R. robusta, a sexually reproducing taxon, is clearly nested within this asexual lineage. Phylogeographic analyses suggest that both dispersal and vicariance played a significant role throughout the evolutionary history of the vagrant Rhizoplaca clade, with most of the dispersal events originating from the Salmon Basin in eastern Idaho – the center of diversity for this group. Despite the fact that wanderlust lichens are dispersal limited due to large, unspecialized vegetative propagules, we inferred multiple dispersal events crossing the Continental Divide. Comparing herbarium records with SDMs suggests that wanderlust lichens don’t fully occupy the areas of highest distribution probability. In fact, documented records often occur in areas predicted to be only marginally suitable. These data suggest a potential mismatch between contemporary habitats outside of the center of diversity in eastern Idaho with the most suitable habitat, adding to the vulnerability of this imperiled complex of endemic lichens.

Identifiable historic and observable factors may predict progression to exfoliation glaucoma in newly-diagnosed exfoliation patients

To identify clinical factors associated with conversion to exfoliation glaucoma (XFG) in exfoliation syndrome (XFS) patients most at risk of progression to XFG within 3 years for increased surveillance and early preventive interventions. A retrospective patient cohort study design was employed. A source population of XFS patients 50 years and older was identified from electronic medical records in the Utah Population Database. From this, 487 study patients with one or more dilated eye exams prior to chart-confirmed XFS onset in 2011 or later, and three or more years of subsequent eye exams, were selected for study. We implemented a binomial linear mixed models with L1-penalized estimation to select variables associated with conversion. Models included a random intercept to account for within-patient correlation for eye-level data. Candidate demographic, lifestyle, systemic and ocular comorbidities data were obtained and diagnoses categorized as binary (history or no history). These potential factors between conversion and non-conversion patients were used in model selection of variables jointly predictive of conversion. Odds ratios and confidence intervals were calculated using the link logit. To determine the main outcome of conversion to XFG following an index diagnosis of XFS compared with nonconversion within 3 years, clinical records of each subject's left and right eyes were assessed to confirm XFS and date of onset and date of XFG onset, if conversion occurred. Clinical measurements, e.g. intraocular pressure (IOP), cup to disc ratio, provider notes and IOP-lowering procedures and medications were used to corroborate conversion status. Eighteen variables jointly predicted XFG conversion within 3 years correctly in 71% of patient eyes. Odds of conversion was highest for exudative age-related macular degeneration (AMD), 2.3-fold (P=0.004). Other predictive variables included nonexudative AMD (P=0.05), primary open angle glaucoma (P<0.001), obstructive sleep apnea (P=0.03), and ocular hypertension (P=0.003) diagnosed prior to XFS onset. We determined a set of clinically relevant factors that predicted which newly-diagnosed XFS patients progressed to XFG within 3 years. A planned validation will independently confirm if these prognostic indicators hold promise in other settings.

Familial autoimmunity and risk of developing immune thrombocytopenia and Evans syndrome.

Immune thrombocytopenia (ITP) and Evans syndrome (ES) are manifestations of immune dysregulation. Genetic variants in immune-related genes have been identified in patients with ITP and especially ES. We aimed to explore familial autoimmunity in patients with ITP and ES to understand possible contributions to chronicity. We assessed family history in two ways: via patient report for ITP and ES and by population-based analysis using the Utah Population Database (UPDB) for ITP. A total of 266 patients with ITP and 21 patients with ES were identified via chart review, and 252 of the 266 patients with ITP were also identified in the UPDB. Chart review showed familial autoimmunity in 29/182 (15.9%) and 25/84 (29.8%) of patients with newly diagnosed+persistent (nd+p) ITP and chronic ITP (cITP), respectively, (p=.009). The UPDB analysis revealed that autoimmunity in relatives of patients with nd+pITP was higher than in relatives of controls (odds ratio [OR]: 1.69 [1.19-2.41], p=.004), but was not significantly increased in relatives of patients with cITP (OR 1.10 [0.63-1.92], p=.734). Incomplete family history in medical records likely contributed to the observed discrepancy. The findings suggest that familial autoimmunity may have a stronger association with the development of ITP rather than its duration. Twelve (57.1%) patients with ES reported autoimmunity in their relatives. UPDB analysis was omitted due to the small number of patients with ES. The use of population databases offers a unique opportunity to assess familial health and may provide clues about contributors to immune dysregulation features within families.

Risk of cardiovascular disease among head and neck cancer survivors: A population-based matched cohort study

BackgroundIn the United States, approximately 63,000 Americans develop head and neck cancer (HNC) annually. Our study aims were to investigate cardiovascular complications and risk factors for development of CVD among HNC survivors. MethodsUtilizing the Utah Populations Database, a total of 1,901 HNC patients diagnosed and 7,796 birth year, sex, and birth state matched individuals from the general population were identified. Multivariate Cox proportional hazard models were used. ResultsWithin the first two years after cancer diagnosis, HNC survivors had a higher likelihood of developing cardiovascular disease (CVD). High Charleston Comorbidity Index (CCI) score at baseline (Hazard Ratio (HR) 1.67, 95 % 1.28–2.17), stage II and IV disease (HR 1.80, 95 % 1.29–2.51), age >=65 years old (HR 2.31, 95 % 1.85–2.88), chemotherapy (HR 1.47, 95 % 1.15–1.88) were associated with increased CVD risk. ConclusionsCompared to the general population, HNC survivors were more likely to develop cardiovascular diseases, particularly if they had the following risk factors: older age, stage II or IV cancer, high baseline CCI score, and chemotherapy were risk factors for development of CVD.

Genitourinary cancer and family: The reverberating psychological and cardiovascular effects of a genitourinary cancer diagnosis on first-degree relatives and spouses.

The psychological and cardiovascular health impacts on family members of patients who have been diagnosed with cancer have not been well characterized. The purpose of this study is to determine whether a family member's cancer diagnosis influences the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients affected by cancer. This retrospective cohort analysis evaluated the risk of psychological illness and cardiovascular disease in first-degree relatives and spouses of patients diagnosed with a genitourinary cancer between 1990 and 2015 compared to relatives of those not diagnosed with a genitourinary cancer. The Utah Population Database was used and familial linkage was determined. Follow-up included 1-, 3-, and 5-year intervals.Patients residing outside of Utah and first-degree relatives and spouses with psychological or cardiovascular disease diagnosed before a family member's cancer diagnosis were excluded. A total of 49,284 patients with a genitourinary cancer were identified with 77,938 first-degree relatives and spouses. A matched control group included 246,775 patients with 81,022 first-degree relatives and spouses. Via Cox proportional hazards models, a 10% increased risk of developing a psychological illness (hazard ratio [HR], 1.10; 95% CI, 1.00-1.20) and a 28% increased risk of developing cardiovascular disease (HR, 1.28; 95% CI, 1.17-1.41) at 1 year after a family member's cancer diagnosis were found. This study provides population-level evidence to support the hypothesis that cancer diagnoses will lead to adverse health outcomes for family members of patients with cancer. Increased clinical attention and support are needed to reduce the harm to families caused by cancer.

Tracking the burden, distribution, and impact of Post-COVID conditions in diverse populations for children, adolescents, and adults (Track PCC): passive and active surveillance protocols

BackgroundTrack PCC includes five geographic surveillance sites to conduct standardized population-based surveillance to estimate and track Post-COVID Conditions (PCC) by age, sex, race/ethnicity, geographic area, severity of initial infection, and risk factors among persons with evidence of SARS-CoV-2 infection (based on the Council of State and Territorial Epidemiologist [CSTE] case definitions for confirmed cases or laboratory-confirmed evidence of infection).MethodsThe study will estimate the incidence, prevalence, including temporal trends, and duration and severity of PCC symptoms, among children, adolescents, and adults. PCCs include a broad range of symptoms and conditions that continue or develop after acute SARS-CoV-2 infection or COVID-19 illness. Surveillance includes both passive and active components for diverse populations in Arizona, Indiana, and Utah as well as the Bronx Borough, NY, and part of Philadelphia County, PA. Passive surveillance will utilize electronic health records and health information exchanges within each site catchment area to longitudinally follow persons with COVID-19 to estimate PCC occurring at least 30 days after acute COVID-19 illness. Active surveillance will utilize self-report of PCCs from detailed surveys of persons ages 7 years and older with evidence of SARS-CoV-2 infection in the past 3 months. Respondents will complete follow-up surveys at 6-, 12- and 18-months post-infection.DiscussionThese data can help identify which groups are most affected by PCC, and what health differences among demographic groups exist, as well as indicate potential barriers to care. These additional levels of granularity can inform public health action and help direct needed clinical care for patients.

Sirt5 regulates chondrocyte metabolism and osteoarthritis development through protein lysine malonylation.

Chondrocyte metabolic dysfunction plays an important role in osteoarthritis (OA) development during aging and obesity. Protein post-translational modifications (PTMs) have recently emerged as an important regulator of cellular metabolism. We aim to study one type of PTM, lysine malonylation (MaK) and its regulator Sirt5 in OA development. Human and mouse cartilage tissues were used to measure SIRT5 and MaK levels. Both systemic and cartilage-specific conditional knockout mouse models were subject to high-fat diet (HFD) treatment to induce obesity and OA. Proteomics analysis was performed in Sirt5 -/- and WT chondrocytes. SIRT5 mutation was identified in the Utah Population Database (UPDB). We found that SIRT5 decreases while MAK increases in the cartilage during aging. A combination of Sirt5 deficiency and obesity exacerbates joint degeneration in a sex dependent manner in mice. We further delineate the malonylome in chondrocytes, pinpointing MaK's predominant impact on various metabolic pathways such as carbon metabolism and glycolysis. Lastly, we identified a rare coding mutation in SIRT5 that dominantly segregates in a family with OA. The mutation results in substitution of an evolutionally invariant phenylalanine (Phe-F) to leucine (Leu-L) (F101L) in the catalytic domain. The mutant protein results in higher MaK level and decreased expression of cartilage ECM genes and upregulation of inflammation associated genes. We found that Sirt5 mediated MaK is an important regulator of chondrocyte cellular metabolism and dysregulation of Sirt5-MaK could be an important mechanism underlying aging and obesity associated OA development.

Family history of type 2 diabetes and the risk of type 2 diabetes among young and middle‐aged adults

AbstractBackgroundThe prevalence of type 2 diabetes has been growing among younger and middle‐aged adults in the United States. A portion of this increase for this age group may be attributable to shared type 2 diabetes risks with family members. How family history of type 2 diabetes history is associated with type 2 diabetes risk among younger and middle‐aged adults is not well understood.MethodsThis population‐based retrospective cohort study uses administrative, genealogical, and electronic medical records from the Utah Population Database. The study population comprises offspring born between 1970 and 1990 and living in the four urban Utah counties in the United States between 1990 and 2015. The sample comprises 360,907 individuals without a type 2 diabetes diagnosis and 14,817 with a diagnosis. Using multivariate logistic regressions, we estimate the relative risk (RR) of type 2 diabetes associated with the number of affected first‐ (FDRs), second‐ (SDRs), and third‐degree (first cousin) relatives for the full sample and for Hispanic‐specific and sex‐specific subsets.ResultsIndividuals with 2+ FDRs with type 2 diabetes have a significant risk of type 2 diabetes in relation to those with no affected FDRs (RR = 3.31 [3.16, 3.48]). Individuals with 2+ versus no SDRs with type 2 diabetes have significant but lower risks (RR = 1.32 [1.25, 1.39]). Those with 2+ versus no affected first cousins have a similarly low risk (RR = 1.28 [1.21, 1.35]). Larger RRs are experienced by males (2+ vs. 0 FDRs, RR = 3.55) than females (2+ vs. 0 FDRs, RR = 3.18) (p &lt; 0.05 for the interaction). These familial associations are partly mediated by the individual's own obesity.ConclusionsThe risks of type 2 diabetes are significantly associated with having affected first‐, second‐, and third‐degree relatives, especially for men. One of the forces contributing to the rising patterns of type 2 diabetes among young and middle‐aged adults is their connection to affected, often older, kin.

Endometriosis Typology and Ovarian Cancer Risk

Endometriosis has been associated with an increased risk of ovarian cancer; however, the associations between endometriosis subtypes and ovarian cancer histotypes have not been well-described. To evaluate the associations of endometriosis subtypes with incidence of ovarian cancer, both overall and by histotype. Population-based cohort study using data from the Utah Population Database. The cohort was assembled by matching 78 893 women with endometriosis in a 1:5 ratio to women without endometriosis. Endometriosis cases were identified via electronic health records and categorized as superficial endometriosis, ovarian endometriomas, deep infiltrating endometriosis, or other. Estimated adjusted hazard ratios (aHRs), adjusted risk differences (aRDs) per 10 000 women, and 95% CIs for overall ovarian cancer, type I ovarian cancer, and type II ovarian cancer comparing women with each type of endometriosis with women without endometriosis. Models accounted for sociodemographic factors, reproductive history, and past gynecologic operations. In this Utah-based cohort, the mean (SD) age at first endometriosis diagnosis was 36 (10) years. There were 597 women with ovarian cancer. Ovarian cancer risk was higher among women with endometriosis compared with women without endometriosis (aHR, 4.20 [95% CI, 3.59-4.91]; aRD, 9.90 [95% CI, 7.22-12.57]), and risk of type I ovarian cancer was especially high (aHR, 7.48 [95% CI, 5.80-9.65]; aRD, 7.53 [95% CI, 5.46-9.61]). Ovarian cancer risk was highest in women with deep infiltrating endometriosis and/or ovarian endometriomas for all ovarian cancers (aHR, 9.66 [95% CI, 7.77-12.00]; aRD, 26.71 [95% CI, 20.01-33.41]), type I ovarian cancer (aHR, 18.96 [95% CI, 13.78-26.08]; aRD, 19.57 [95% CI, 13.80-25.35]), and type II ovarian cancer (aHR, 3.72 [95% CI, 2.31-5.98]; aRD, 2.42 [95% CI, -0.01 to 4.85]). Ovarian cancer risk was markedly increased among women with ovarian endometriomas and/or deep infiltrating endometriosis. This population may benefit from counseling regarding ovarian cancer risk and prevention and could be an important population for targeted screening and prevention studies.

Breast Cancer is Increased in Women with Primary Ovarian Insufficiency.

DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk. We hypothesized that a subset of women with POI and family members would have increased risk for cancer. Case-control population-based study using records from 1995-2022. Two major Utah academic healthcare systems serving 85% of the state. Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database. Cancer diagnoses were identified using the Utah Cancer Registry. The relative risk of cancer in women with POI and relatives was estimated by comparison to population rates. Whole genome sequencing was performed on a subset of women. Breast cancer was increased in women with POI (OR [95%CI] 2.20 [1.30, 3.47]; p=0.0023) and there was a nominally significant increase in ovarian cancer. Probands with POI were 36.5±4.3 years and 59.5±12.7 years when diagnosed with POI and cancer, respectively. Causal and candidate gene variants for cancer and POI were identified.Among second-degree relatives of these women, there was an increased risk of breast (1.28 [1.08, 1.52]; p=0.0078) and colon cancer (1.50 [1.14, 1.94]; p=0.0036). Prostate cancer was increased in first- (1.64 [1.18, 2.23]; p=0.0026), second- (1.54 [1.32, 1.79]; p<0.001), and third-degree relatives (1.33 [1.20, 1.48]; p<0.001). Data suggest common genetic risk for POI and reproductive cancers. Tools are needed to predict cancer risk in women with POI and potentially to counsel about risks of hormone replacement therapy.

Chasing shadows: Investigating X chromosome mediation in late-onset Alzheimer’s disease

Alzheimer&amp;rsquo;s disease (AD) is a major cause of dementia. While maternal inheritance has been recognized for late-onset AD (LOAD), risk factors have not been identified consistently on the X chromosome. We recently developed a new method to identify an apparent risk of 70% mediated by the X chromosome in newly-presenting cognitive disorders clinic patients with amnestic mild cognitive impairment (aMCI) or early LOAD with unilateral parental lineage for AD or dementia. We sought to confirm our preliminary findings in the Utah Population Database (UPDB). We obtained previously published aggregate data on the risk of AD in the UPDB based on family history, stratified the data by the sex of the proband, and analyzed them using the new method. The X chromosome-attributable relative risk was estimated by calculating the following: Odds ratio (OR) = (women with paternal lineage: Women with maternal lineage)/(men with paternal lineage: Men with maternal lineage). The proportion of genetic risk attributable to the X chromosome is equal to (OR-1)/OR. The analysis did not reveal any risk mediated by the X chromosome, and the null result could be attributed to methodological limitations. Factors that impact the initial or early presentation (incidence) of LOAD, which are appropriate for consideration as risk factors, may not be detectable in a (prevalent) population of deceased individuals. Thus, epidemiological evidence for the contribution of the X chromosome to the development of LOAD will need to be sought prospectively in incident patient populations with newly diagnosed, biologically-confirmed aMCI or LOAD.

Preoperative opioid use and its association with postoperative complications

ABSTRACT Background The negative impact of opioid use in the U.S. has led providers to seek alternative methods for pain control. More specifically, preoperative opioid usage has been demonstrated to adversely affect patients and clinical outcomes. This study aims to assess the extent of the relationship between preoperative opioid use on postoperative outcomes across surgical disciplines using statewide population databases. Methods The study used the Utah All Payers Claims Database and Utah Population Database to identify a cohort of adult patients who underwent a single surgery between 2013 and 2016 and had continuous insurance enrollment. Preoperative opioid prescription within one year prior to the index surgery was the independent variable, while complications and hospital admissions one year following the index surgery were the primary outcomes. Results Our model of 18,647 patients found that the odds of any complication with preoperative opioid use was 1.28. Depression (OR 1.17) and drug misuse (OR 1.41) were also associated with a higher risk of postoperative complications. Rates of hospital readmission in the preoperative opioid use group compared to the opioid naïve group were increased (19.43% vs. 12.44%, p < .01). Conclusion The data can be used to guide patient-physician conversations and better inform prescribing habits perioperatively.

Characteristics of a transgender and gender-diverse patient population in Utah: Use of electronic health records to advance clinical and health equity research.

Transgender and gender-diverse (TGD) people, individuals whose gender identity differs from their sex assigned at birth, face unique challenges in accessing gender-affirming care and often experience disparities in a variety of health outcomes. Clinical research on TGD health is limited by a lack of standardization on how to best identify these individuals. The objective of this retrospective cohort analysis was to accurately identify and describe TGD adults and their use of gender-affirming care from 2003-2023 in a healthcare system in Utah, United States. International Classification of Disease (ICD)-9 and 10 codes and surgical procedure codes, along with sexual orientation and gender identity data were used to develop a dataset of 4,587 TGD adults. During this time frame, 2,985 adults received gender-affirming hormone therapy (GAHT) and/or gender-affirming surgery (GAS) within one healthcare system. There was no significant difference in race or ethnicity between TGD adults who received GAHT and/or GAS compared to TGD adults who did not receive such care. TGD adults who received GAHT and/or GAS were more likely to have commercial insurance coverage, and adults from rural communities were underrepresented. Patients seeking estradiol-based GAHT tended to be older than those seeking testosterone-based GAHT. The first GAS occurred in 2013, and uptake of GAS have doubled since 2018. This study provides a methodology to identify and examine TGD patients in other health systems and offers insights into emerging trends and access to gender-affirming care.

Mortality and Causes of Death Among Individuals With Keratoconus.

The purpose of this study was to determine whether there is an increased risk of mortality among individuals with keratoconus. This was a retrospective, case-control study using the Utah Population Database. Cases were defined as individuals diagnosed with keratoconus from 1996 to 2020 and were matched 5:1 with controls on birth year, sex, whether born in Utah, and follow-up time in Utah. Individuals diagnosed with trisomy 21 or connective tissue disease were excluded. Main outcome measures were the all-cause and cause-specific mortality among keratoconus cases compared with matched controls. Cox regression models were used, additionally adjusting for race and ethnicity. A total of 7847 keratoconus cases and 38,597 controls were studied in the final analyses. The mean age at index diagnosis was 43 ± 17 years, and mean age at last follow-up was 54 ± 17 years for both cases and controls. At last follow-up, 92% of cases were living compared with 91% of controls. After adjusting for covariates, there were no significant differences in all-cause mortality (P = 0.161), mortality from natural causes (0.222), or mortality from unnatural causes (P = 0.494) between cases and controls. When analyzed according to specific causes of death, keratoconus cases had a higher mortality risk from diseases of the nervous system and sense organs compared with their matching controls (hazard ratio 1.59; 95% confidence interval, 1.19-2.11; P = 0.002). There was no evidence of an increased risk of mortality among individuals with keratoconus. There may be an increased risk of death due to diseases of the nervous system and sense organs among individuals with keratoconus.

Neighborhood built environment, obesity, and diabetes: A Utah siblings study

BackgroundThis study utilizes innovative computer vision methods alongside Google Street View images to characterize neighborhood built environments across Utah. MethodsConvolutional Neural Networks were used to create indicators of street greenness, crosswalks, and building type on 1.4 million Google Street View images. The demographic and medical profiles of Utah residents came from the Utah Population Database (UPDB). We implemented hierarchical linear models with individuals nested within zip codes to estimate associations between neighborhood built environment features and individual-level obesity and diabetes, controlling for individual- and zip code-level characteristics (n = 1,899,175 adults living in Utah in 2015). Sibling random effects models were implemented to account for shared family attributes among siblings (n = 972,150) and twins (n = 14,122). ResultsConsistent with prior neighborhood research, the variance partition coefficients (VPC) of our unadjusted models nesting individuals within zip codes were relatively small (0.5%–5.3%), except for HbA1c (VPC = 23%), suggesting a small percentage of the outcome variance is at the zip code-level. However, proportional change in variance (PCV) attributable to zip codes after the inclusion of neighborhood built environment variables and covariates ranged between 11% and 67%, suggesting that these characteristics account for a substantial portion of the zip code-level effects. Non-single-family homes (indicator of mixed land use), sidewalks (indicator of walkability), and green streets (indicator of neighborhood aesthetics) were associated with reduced diabetes and obesity. Zip codes in the third tertile for non-single-family homes were associated with a 15% reduction (PR: 0.85; 95% CI: 0.79, 0.91) in obesity and a 20% reduction (PR: 0.80; 95% CI: 0.70, 0.91) in diabetes. This tertile was also associated with a BMI reduction of −0.68 kg/m2 (95% CI: −0.95, −0.40) ConclusionWe observe associations between neighborhood characteristics and chronic diseases, accounting for biological, social, and cultural factors shared among siblings in this large population-based study.

Utah Latina/o/x suicide decedents less likely to die by firearm, even in rural areas: examining population-wide data from the Utah Office of the Medical Examiner.

Suicide death remains a significantly rarer event among Latina/o/x populations compared to non-Latina/o/x populations. However, the reasons why Latina/o/x communities experience relatively lower suicide rates are not fully understood. Critical gaps exist in the examination of Latina/o/x suicide death, especially in rural settings, where suicide death by firearm is historically more common within non-Latina/o/x populations. We tested whether the prevalence of Latina/o/x firearm suicide was meaningfully different in urban and rural environments and from non-Latino/a/x decedents when controlling for age, sex, and a social deprivation metric, the Area Deprivation Index. Suicide death data used in this analysis encompasses 2,989 suicide decedents ascertained in Utah from 2016 to 2019. This included death certificate data from the Utah Office of the Medical Examiner on all Utah suicide deaths linked to information by staff at the Utah Population Database. Compared to non-Latina/o/x suicide decedents, Latina/o/x suicide decedents had 34.7% lower adjusted odds of dying by firearm. Additionally, among the firearm suicide decedents living only in rural counties, Latina/o/x decedents had 40.5% lower adjusted odds of dying by firearm compared to non-Latina/o/x suicide decedents. The likelihood of firearm suicide death in Utah differed by ethnicity, even in rural populations. Our findings may suggest underlying factors contributing to lower firearm suicide rates within Latina/o/x populations, e.g., aversion to firearms or less access to firearms, especially in rural areas, though additional research on these phenomena is needed.

Identification of rare genetic variants for rotator cuff tearing and repair in high-risk pedigrees

BackgroundCommon genetic variants with small effect sizes have been associated with rotator cuff tearing although very few rare, highly penetrant variants have been identified. The purpose of this pilot study was to identify dominant coding variants that segregated with affected individuals in pedigrees at high risk for rotator cuff tears. We hypothesize that rare variants contribute to symptomatic rotator cuff tears and that they can be identified in related cases with a full-thickness tear requiring surgical management. MethodsWe used the Utah Population Database (UPDB) to identify pedigrees that exhibited a significant excess of individuals who had undergone surgical repair of a full thickness rotator cuff tear. We analyzed whole exome sequence analysis to identify rare coding variants in 9 independent affected cousin pairs (first or second cousins) who had undergone arthroscopic surgery for repair of a full thickness rotator cuff tear (mean age at diagnosis 68 years). Validation of association of the candidate variants with risk for rotator cuff tearing was accomplished utilizing data from the UK Biobank and a separate cohort of unrelated cases of full thickness rotator cuff tears. ResultsA total of 82 rare (minor allele frequency <0.005) coding variants were identified as shared in at least one cousin pair affected with full thickness rotator cuff tearing belonging to a high-risk pedigree, which included variants in RUNX1, ADAM12, TGFBR2, APBB1, PDLIM7, LTBP1, MAP3K4 and MAP3K1. Analysis of 39 of these variants with data available in the UK Biobank (3,899 cases with rotator cuff injury and 11,697 matched controls; mean case age 59.9 years) identified a significant association with the APBB1 gene (OR=2.37, p=0.007, uncorrected). The PDLIM7 allele was found to be in significant excess in rotator cuff tear cases in a separate cohort of Utah patients with full thickness rotator cuff tears (10 carriers out of 458 independent, unrelated patients; minor allele frequency of 0.022) compared to a minor allele frequency of 0.0058 for the European (non-Finnish) control population rate (749 carriers out of 128612 tested) (chi square test: 19.3 (p<0.001). DiscussionThe analysis of closely related individuals with confirmed full thickness rotator cuff tears from high-risk pedigrees has identified 82 rare, shared candidate genetic predisposition coding variants. Association of the PDLIM7 allele with risk for tear was confirmed in an independent cohort of rotator cuff tears. Further analysis of the variant alleles is required for confirmation of these genes in rotator cuff tearing.

Teaching evolution: attitudes & strategies of educators in Utah – an update 20 years later

ABSTRACT Previous research on evolution education in Utah college biology courses highlighted how frequently professors faced student challenges to evolution and examined the strategies they used to deal with those challenges. In the twenty years since that study, the population of Utah has become less religious and more diverse. Meanwhile, the US population has become more accepting of evolution. To investigate college biology evolution education in Utah’s current demographic and ideological climate, we repeated research completed in 2002. Statistical analysis of group differences between the 2002 sample (N = 78) and the 2022 sample (N = 135) suggests that current college biology instructors experience fewer challenges to evolution. Strategies for dealing with student challenges also shifted. The 2022 sample reported greater reliance on presenting religion and science as not mutually exclusive and highlighting evolution as science, while reporting reduced emphasis on presenting evolution and religion as distinct concepts. The recent sample had more than double the proportion of women as the previous sample, reflecting a nationwide trend of stronger representation by women in STEM fields. Our findings suggest that instructors who teach evolution should periodically examine their methods to ensure they are teaching in a way that connects with current students.