non-Hispanic Caucasians Research Articles

Determination and use of haplotypes: Ethnic comparison and association of the lipoprotein lipase gene and coronary artery disease in Mexican-Americans

Purpose: To illustrate an approach of deriving haplotypes for genetic association studies, using the lipoprotein lipase (LPL) gene and coronary artery disease.Methods: Six polymorphisms sufficient to distinguish the most common haplotypes in the 3′ end of LPL were identified by genotyping 10 polymorphisms in a small pilot population. These were used to haplotype LPL in large family samples of Mexican-Americans and non-Hispanic Caucasians. A case-control association study was performed comparing Mexican-Americans with and without coronary artery disease.Results: The two ethnic groups exhibited significant genetic differences. Among Mexican-Americans, homozygosity for LPL haplotype 1 was protective against coronary artery disease (OR = 0.50, 95% CI 0.27–0.91).Conclusion: This study outlines the haplotype structure of the LPL gene, illustrates the utility of haplotype-based analysis in association studies, and demonstrates the importance of defining haplotype frequencies for different ethnic groups.

Trends and disparities in osteoarthritis prevalence among US adults, 2005\u20132018

Studies reporting trends and disparities of osteoarthritis (OA) in the United States are limited. We aimed to examine trends and disparities of OA prevalence among US adults, from 2005 to 2018. Continuous National Health and Nutrition Examination Survey (NHANES) data from 2005–2006 to 2017–2018 were analyzed. Age-adjusted and self-reported OA prevalence, stratified by race/ethnicity and socioeconomic status (SES), was calculated separately for men and women. The linear trend and the association between the survey cycles and OA prevalence were assessed. Age-adjusted and self-reported OA prevalence linearly increased in the seven survey cycles (both Plinear trend ≤ 0.0002) in men and women. Non-Hispanic Caucasians (both Plinear trend ≤ 0.0001) in both genders and Non-Hispanic African Americans women (Plinear trend ≤ 0.0001) had significantly increasing linear trends in OA prevalence. In addition, people with lower SES had a lower age-adjusted prevalence of self-reported OA when compared to those with higher SES. The increasing linear trends still existed among both men and women after adjusting for multiple confounders (both Plinear trend ≤ 0.002). There were significant rising trends and disparities in self-reported OA prevalence among US men and women between 2005 and 2018.

Clinical Presentation of Hepatocellular Carcinoma in African Americans vs. Caucasians: A Retrospective Analysis.

Hepatocellular carcinoma (HCC) remains an important form of cancer-related morbidity and mortality in the U.S. and worldwide. Previous U.S.-based studies on survival suggest ethnic disparities in HCC patients, but the complex interplay of multiple factors that contribute are still incompletely understood. Here we considered the influences of risk factors contributing towards HCC survival, including ethnic background, over ten years at a premier academic medical center with a majority (57.20%) African American (AA) population. Retrospective HCC data were collected from 2008–2018 at LSUHSC-Shreveport, an urban tertiary medical center. Data included demographics, comorbidities, liver disease characteristics, and tumor parameters. Statistical analysis was performed using Chi Square and one-way ANOVA. Results: 229 HCC patients were identified (male 78.6%). The mean HCC age at diagnosis was 61 years (SD = 7.3). Compared to non-Hispanic Caucasians (42.7%), AA patients (57.2% of total) were older at presentation, had more frequent diabetes/dyslipidemia/NAFLD (45 (34.3%) compared with 19 (19.3%) in non-Hispanic Caucasians, p = 0.02), and had a larger HCC burden at diagnosis. We conclude that compared to white patients, despite having similar BMI and MELD scores and rates of portal vein thrombosis, AA patients with HCC in our cohort were older at presentation, had a significantly increased incidence of modifiable metabolic risk factors including diabetes, higher AFP values, increased incidence of gallstones, and larger sized HCCs, and were more likely to be outside Milan criteria. These findings have important prognostic and diagnostic implications for developing a more targeted HCC surveillance program.

The Effect of Treatment Facility, Race, and Chemoradiation on Survival for Signet Ring Cell Carcinoma of the Esophagus: An Analysis of the National Cancer Database

Background: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility. Methods: There were 2,021 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance of treatment facility type and other variables. Results: The cohort mostly received treatment at academic centers (47.7%). As age increased, mortality also increased (HR=1.01; 95% CI:1.01-1.02, p<0.001). Africans Americans (HR=1.44; 95% CI:1.02-2.02, p=0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programmes (HR=0.73; 95% CI:0.64-0.84, p<0.001) and integrated cancer programmes (HR=0.69; 95% CI:0.58-0.83, p=0.008). Neoadjuvant chemoradiation resulted decreased mortality when compared to adjuvant chemoradiation (HR=1.41; 95% CI:1.21-1.63, p<0.001) and no chemoradiation (HR=1.84; 95% CI:1.58- 2.14, p<0.001). Conclusion: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans, increasing tumor stage, no and adjuvant chemoradiation, and comorbidities with Charlson-Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.

Prevalence and Susceptibility to Hepatitis B virus and the Need for Community Health Education in Milwaukee's Hmong Community.

Chronic Hepatitis B virus infection, the leading cause of hepatocellular carcinoma worldwide, disproportionately affects Asian Pacific Islanders (APIs) within the USA. Among APIs, the Hmong have one of the highest rates of chronic HBV infection-up to 18% compared to 0.1% for non-Hispanic Caucasians. This study sought to estimate the prevalence of HBV infection and assess the need for community HBV education within Milwaukee County's Hmong. Between 3/2013 and 12/2019, 287 Hmong participants were screened for HBV and 271 were provided targeted HBV education to evaluate its impact on HBV knowledge. Among participants screened, 178 (62%) were immune; 77 (27%) susceptible; 27 (9%) positive; and 5 (2%) in a "gray zone." Targeted health education showed statistically significant improvement in HBV knowledge. With 38% lacking immunity to HBV and 9% with active infection, there remains a significant need for HBV screening, vaccination, and education in Milwaukee's Hmong community.

Health Disparities among adults cared for at an urban cystic fibrosis program

BackgroundEvidence is conflicting regarding differential health outcomes in racial and ethnic minorities with cystic fibrosis (CF), a rare genetic disease affecting approximately 28,000 Americans. We performed a cross-sectional analysis of health outcomes in Black/Latinx patients compared with non-Hispanic Caucasian patients cared for in a CF center in New York City. Adult patients enrolled in the CF Foundation Patient Registry at the Columbia University Adult CF Program and seen at least once during 2019 were included. Health metrics were compared between Black/Latinx and non-Hispanic Caucasian patients.Results262 patients were eligible. 39 patients (15%) identified as Black/Latinx or non-Hispanic Caucasian. Descriptive statistics are reported with mean (standard deviation). Current age was 35.9 (13.3) years for non-Hispanic Caucasian and 32.0 (9.3) years for Black/Latinx patients (p = 0.087). Age of diagnosis did not differ between groups; 9.56 (15.96) years versus 11.59 (15.8) years for non-Hispanic Caucasian versus Black/Latinx respectively (p = 0.464). Pulmonary function, measured as mean forced expiratory volume in one second (FEV1) was 70.6 (22.5) percent predicted in non-Hispanic Caucasian versus 59.50 (27.9) percent predicted in Black/Latinx patients (p = 0.010). Number of visits to the CF clinic were similar between groups. When controlled for age, gender, co-morbidities, median income, and insurance status, there was a continued association between minority status and lower FEV1.ConclusionsMinorities with CF have significantly lower pulmonary function, the major marker of survival, than non-Hispanic Caucasians, even when controlled for a variety of demographic and socioeconomic factors that are known to affect health status in CF. Significant health disparities based on race and ethnicity exist at a single CF center in New York City, despite apparent similarities in access to guideline based care at an accredited CF Center. This data confirms the importance of design of culturally appropriate preventative and management strategies to better understand how to direct interventions to this vulnerable population with a rare disease.

Prevalence Trend and Disparities in Rheumatoid Arthritis among US Adults, 2005–2018

Rheumatoid arthritis (RA) trends among US adults and disparities in RA patients in recent years have not been well described. We aimed to examine the trend of RA prevalence and disparities among US adults. Data from the National Health and Nutrition Examination Survey (NHANES) of the years 2005–2018 were analyzed to examine the self-reported RA prevalence trend. Age-adjusted RA prevalence stratified by race/ethnicity and socioeconomic status (SES), as well as associated linear trends, were calculated for both genders. The multivariable adjustment was used to evaluate the association between race, SES, and RA. During 2005–2018, there was no significant linear trend in the age-adjusted self-reported RA prevalence among men and women, but significant differences among people from different races, educational levels, and family poverty income ratio (PIR) groups were observed. The RA rate difference was significant for both genders and between Non-Hispanic Caucasians and Non-Hispanic African Americans (both p-value ≤ 0.001). Both men and women with a higher educational level and a higher PIR had a lower age-adjusted RA rate. Age-adjusted RA prevalence fluctuated for both men and women during 2005–2018. Non-Hispanic African Americans and people with low SES had significantly higher age-adjusted RA prevalence and RA risk.

Genetic Factors Associated with COPD Depend on the Ancestral Caucasian/Amerindian Component in the Mexican Population.

Genetic variability influences the susceptibility to and severity of complex diseases; there is a lower risk of COPD in Hispanics than in non-Hispanic Caucasians. In this study, we included 830 Mexican-Mestizo subjects; 299 were patients with COPD secondary to tobacco smoking, and 531 were smokers without COPD. We employed a customized genotyping array of single nucleotide polymorphisms (SNPs). The population structure was evaluated by principal component analysis and allele association through a logistic regression model and haplotype identification. In this study, 118 individuals were identified with a high Caucasian component and 712 with a high Amerindian component. Independent of the ancestral contribution, two SNPs were associated with a reduced risk (p ≤ 0.01) of developing COPD in the CYP2A6 (rs4105144) and CYP2B6 (rs10426235) genes; however, a haplotype was associated with an increased risk of COPD (p = 0.007, OR = 2.47) in the CHRNA5-CHRNA3 loci among smokers with a high Caucasian component. In Mexican-Mestizo smokers, there are SNPs in genes that encode proteins responsible for the metabolism of nicotine associated with a lower risk of COPD; individuals with a high Caucasian component harboring a haplotype in the CHRNA5-CHRNA3 loci have a higher risk of suffering from COPD.

Targeting mTOR and DNA repair pathways in residual triple negative breast cancer post neoadjuvant chemotherapy

Triple-negative breast cancer (TNBC) patients who do not achieve pathologic complete response post neoadjuvant chemotherapy have a poor prognosis. Alteration in PI3K/mTOR plus DNA repair pathways are some of the major mechanisms of chemotherapy resistance. We designed an open-label phase II clinical trial to evaluate if the combination of everolimus (mTOR inhibitor) plus cisplatin (interferes with DNA function) will improve the rate of pathologic response, as assessed by residual cancer burden (RCB). Twenty-four Stage II/III TNBC patients with residual cancer > 1 cm post neoadjuvant anthracycline and taxane-based chemotherapy were enrolled. Patients received everolimus daily orally at 10 mg for 12 weeks and cisplatin IV at 20 mg/m2 weekly for 4 cycles (21-day cycle), until definitive surgery. The primary endpoint was the rate of RCB-0-I at the surgery. The median age of the whole cohort was 50.1 years, with 66.7% non-Hispanic Caucasians. Of the 24 patients enrolled, 22 were included in the efficacy analysis. Twenty-one patients underwent definitive surgery while one patient developed distant metastasis. Five patients had RCB-I at surgery, a response rate of 23% (5/22). Patients with germline PALB2 mutation or somatic PI3KCA mutation had a pathologic response, achieving RCB-I at the surgery. Three patients had metaplastic histology achieving RCB-I at the surgery. Estimated OS at 1 year was 100% in the RCB-I group vs. 76.5% in others, which was not statistically significant due to the small sample size. Certain cohorts including PALB2 germline mutation carrier and somatic PI3KCA mutations warrant further investigation.Trial registration: Clinicaltrials.gov identifier: NCT01931163. https://clinicaltrials.gov/ct2/show/NCT01931163.

Outcomes in Hispanics With COVID-19 Are Similar to Those of Caucasian Patients in Suburban New York.

BackgroundDespite reported higher rates and worse outcomes due to COVID‐19 in certain racial and ethnic groups, much remains unknown. We explored the association between Hispanic ethnicity and outcomes in COVID‐19 patients in Long Island, New York.MethodsWe conducted a retrospective cohort study of 2,039 Hispanic and non‐Hispanic Caucasian patients testing positive for SARS‐CoV‐2 between March 7 and May 23, 2020, at a large suburban academic tertiary care hospital near New York City. We explored the association of ethnicity with need for intensive care unit (ICU), invasive mechanical ventilation (IMV), and mortality.ResultsOf all patients, 1,079 (53%) were non‐Hispanic Caucasians and 960 (47%) were Hispanic. Hispanic patients presented in higher numbers than expected for our catchment area. Compared with Caucasians, Hispanics were younger (45 years vs. 59 years), had fewer comorbidities (66% with no comorbidities vs. 40%), were less likely to have commercial insurance (35% vs. 59%), or were less likely to come from a nursing home (2% vs. 10%). In univariate comparisons, Hispanics were less likely to be admitted (37% vs. 59%) or to die (3% vs. 10%). Age, shortness of breath, congestive heart failure (CHF), coronary artery disease (CAD), hypoxemia, and presentation from nursing homes were associated with admission. Male sex and hypoxemia were associated with ICU admission. Male sex, chronic obstructive pulmonary disease, and hypoxemia were associated with IMV. Male sex, CHF, CAD, and hypoxemia were associated with mortality. After other factors were adjusted for, Hispanics were less likely to be admitted (odds ratio = 0.62, 95% confidence interval = 0.52 to 0.92) but Hispanic ethnicity was not associated with ICU admission, IMV, or mortality.ConclusionsHispanics presented at higher rates than average for our population but outcomes among Hispanic patients with COVID‐19 were similar to those of Caucasian patients.

Abstract A12: Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma

Abstract Introduction: Uveal melanoma (UM) is a rare melanoma; only 5% of cases at initial presentation have distant metastasis. As approximately 50% of patients will develop metastatic disease, there is a need to detect minimal residual disease (MRD). Liquid biopsy using circulating tumor cells (CTCs) has been evaluated in multiple tumors; high CTC count predicts for increased risk of metastasis. We conducted a pilot study to check feasibility of CTCs in UM and evaluate if CTCs vary with risk status in early-stage UM. Methods: We enrolled 40 UM patients ≥18 years, after obtaining informed consent in an IRB-approved protocol from 12/1/2014 to 2/1/2018. Peripheral blood was obtained to detect CTCs using CellSearch Circulating Melanoma Cell Assay. Demographic information, mutational analysis, date of diagnosis of primary UM or metastasis, and dates of CTC collection were collected. Risk stratification was done by gene expression profiling (GEP) by DecisionDX-UM assay. Landmark overall survival (OS) was calculated using “Landest” R package comparing CTC detected vs. not detected in early-stage UM. Results: 39 patients were available for analysis. Median age of whole cohort was 52 years (20-83 years), 100% were non-Hispanic Caucasians, and 44% were male and 56% female. 20 patients had early-stage vs. 19 patients had metastatic disease at enrollment. 87% (13/15) of early-stage disease had class II disease. GNAQ & GNA11 mutations were present in 36% (12/39) and 13% (5/29), respectively. At initial blood draw, 36% of the patients had detectable CTCs [30% (6/20) in early stage vs. 42% (8/19) in metastatic], which increased to 54% at median study follow-up of 16.4 months [40% (8/20) in early stage vs. 68% (13/19) in metastatic]. Mean CTCs were higher in metastatic (9) vs. early stage (1.83) (p>0.05). 5 patients in early-stage disease developed distant metastasis; 60% (3/5) had detectable CTCs before radiographic detection of metastasis. Out 5, 80% had class II disease and 20% had unknown GEP. Landmark overall survival (from study enrollment) at 24 months was statistically worse in CTC detected vs. not detected in early-stage UM (P<0.05). Conclusion: CTCs are more frequently detected in metastatic compared to early-stage UM. In early-stage UM, presence of CTCs predicts for increased risk of metastatic disease and is associated with worse outcome. Citation Format: Jason Roszik, Dan Gombos, Joshua Upshaw, Vanessa Sarli, Salyna Meas, Anthony Lucci, Carolyn Hall, Sapna Patel, Kartik Anand. Presence of circulating tumor cells is an adverse risk factor for early-stage uveal melanoma [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A12.

Variants of opioid genes and response to treatment of opioid use disorder with buprenorphine-naloxone versus extended-release naltrexone in Caucasians

ABSTRACT Background: Sublingual buprenorphine-naloxone (BUP-NX), an FDA-approved treatment for opioid use disorder (OUD), combines buprenorphine (a partial mu/kappa agonist) with naloxone (a mu/ kappa antagonist). Extended-release injection naltrexone (XR-NTX; a mu receptor antagonist and kappa receptor partial agonist) is also an FDA-approved treatment for OUD. However, while some patients respond well to these medications, many others leave treatment and relapse. Objectives: Determine whether gene variants in the opioid gene system are associated with better or worse treatment response. Methods: In a 24-week, multisite, randomized, comparative effectiveness trial of daily, sublingual self-administration of BUP-NX versus monthly injection of XR-NTX conducted in the National Drug Abuse Clinical Trials Network, DNA was collected and four opioid gene variants were evaluated: (1) mu opioid receptor 118A>G; (2) 68-bp repeat in prodynorphin; (3) prodynorphin SNP rs910080; and (4) kappa opioid receptor SNP rs6473797. In non-Hispanic Caucasians (N = 334), two outcomes measures were assessed: received first dose (yes/no) and received last dose (yes/no). Separate logistic regressions were used to model each outcome measure as a function of treatment (XR-NTX vs BUP-NX), each gene variant, and their interaction. Results: There were no significant main effects of gene variant on receiving first dose or last dose. There were also no significant gene variant by treatment interactions. Conclusions: The outcome of treatment of OUD with medications is likely a complex function of multiple factors, including environmental, psychosocial, and possibly genetic, such that major effects of genetic variants may be unlikely.

Substituting imputation of HLA antigens for high-resolution HLA typing: Evaluation of a multiethnic population and implications for clinical decision making in transplantation.

Molecular mismatch analysis for assessment of histocompatibility in transplantation requires high-resolution HLA typing. Algorithms to "guesstimate" high-resolution from low-resolution typing exist, but their accuracy remains unknown. We converted high-resolution, sequence-based, HLA typing of 310 subjects from an ethnically heterogeneous population to low-resolution equivalents and tested the ability of the NMDP HaploStats and HLA Matchmaker programs to impute/reproduce the measured high-resolution HLA type, using the more common "winner-takes-all" approach. Only 35.6% of the HaploStats imputed HLA-A, -B, -C, -DRB1, and -DQB1 haplotypes had no mistakes, and the accuracy was significantly lower for non-Caucasians (29.1%) compared to Caucasians (45.2%) (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.3-0.8; P=.004). HLA Matchmaker was not able to provide high-resolution haplotypes for 45.2% of Caucasian subjects and 63.5% of non-Caucasian subjects (P=.002). Of those with an imputed result, only 10.3% of Caucasians and 4.8% of non-Caucasians had accurate 10-allele high-resolution output. Eplet analysis revealed additional, inaccurate eplets in 37% of individuals, with 22.5% showing at least 2 additional, inaccurate eplets; incorrect eplets were more common among non-Caucasians (OR, 1.8; 95% CI, 1.1-2.9; P=.018). Given this high error rate, caution should be taken before using imputation tools for clinical or research purposes, especially for non-Caucasian individuals.

Abstract B129: Does insurance status explain the racial disparity in survival outcome seen in upper aerodigestive tract cancers in the United States?

Abstract Upper Aerodigestive tract (UADT) cancers are primarily squamous cell carcinomas that affect the oral cavity (hard palate, front 2/3 of tongue, gums, mucosal lining of lips and cheeks, and the floor of the mouth), oropharynx (base of the tongue, soft palate, and tonsils), hypopharynx, larynx (epiglottis and vocal cords), and the upper third of the esophagus with a five-year survival rate of 65.3% for oral cavity and pharyngeal cancers. If the cancer is detected during the localized stage, the survival rate improves to 84.4% (SEER 18 2009-2015).There have been several risk factors implicated in the pathogenesis of UADT cancers such as, male gender, smoking, alcohol use, and infection with human papilloma virus (HPV) for oropharyngeal cancers. The current literature suggests that regardless of stage people of African descent have a lower incidence of UADT cancers, but higher mortality rates compared to Caucasians. There are many proposed explanations for this paradoxical trend seen in African Americans. However, there is a paucity of research addressing this problem. We seek to understand if socioeconomic status is the underlying factor driving this disparity. We analyzed de-identified data collected from the Surveillance, Epidemiology, and End Results (SEER) program for 114,510 UADT cancer patients diagnosed from 2007-2016. We hypothesized that people who were uninsured or on Medicaid would have a life expectancy that was significantly reduced compared to those that had private insurance or Medicare regardless of race, tumor grade, gender or site of the cancer. Our study design is retrospective cohort. Our multivariate analysis model utilizes survival analysis techniques such as Kaplan-Meier survival, hazard curves and proportional hazards regression to analyze the survival time of our patients as a function of demographic and clinical variables. Survival months ranged from 0 to 119 months, with 25,122 patients experiencing death due to UADT cancers. The proportional hazards regression revealed that across all insurance groups (Insured, Uninsured, Medicaid, and Unknown) the survival time for Non-Hispanic Black People was significantly reduced compared to the other race/ethnicities (Asians, Caucasians, Hispanics (all races)) with Non-Hispanic Caucasians having the highest survival rate. Determining that the racial disparity exists regardless of insurance status, tumor grade, gender, and site of cancer can guide future researchers to focus on biological differences or other factors such as lack of access to care that underlie disease survival for UADT cancers. Citation Format: Joycemary G Amponsem, Dana Marshall, Derek Wilus, Mohammad Tabatabai. Does insurance status explain the racial disparity in survival outcome seen in upper aerodigestive tract cancers in the United States? [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr B129.

Racial disparities in comorbid conditions among patients undergoing thyroidectomy for Graves’ disease: An ACS-NSQIP analysis

BackgroundStudies indicate that racial disparities exist in the presentation and outcomes of patients undergoing thyroidectomy for cancer and benign disease. We examined the relationship between race, pre-operative characteristics and outcomes in patients undergoing thyroidectomy for GD. MethodsPatients were identified from the 2013–2016 American College of Surgeons NSQIP database using ICD-9/10 codes consistent with diffuse toxic goiter. ResultsAA patients were more likely to have an ASA classification of ≥3 (41% vs 30%, p < 0.001), a higher rate of CHF (2.1% vs 0.5%, p = 0.01), hypertension (46% vs 32%, p < 0.001) and dyspnea (10% vs 5%, p < 0.001) compared to Non-Hispanic Caucasians (NH–C) patients. Complications were higher in patients with ASA≥3 and CHF but not affected by race. ConclusionsAnalysis of a national database of thyroidectomy for GD revealed a higher burden of preoperative comorbidities in AA patients compared to other races, although race was not an independent predictor of outcomes.

Genome-Wide Association Study Identifies SLAMF1 Affecting the Rate of Memory Decline.

As cognitive function declines with age, identifying factors affecting the trajectory of cognitive decline is an indispensable step toward developing intervention strategies to improve the quality of the elderly life. We performed a genome-wide association study (GWAS) focusing on memory function to explore single nucleotide polymorphisms (SNPs) associated with the rate of memory decline. Seven hundred and nine eligible non-Hispanic Caucasians from the Alzheimer's Disease Neuroimaging Initiative (ADNI) were included for analysis after quality control. GWAS was performed with linear regression. We subsequently tested whether the associations remained significant in subgroup analysis and also examined the impact of SNPs on the longitudinal changes in other neuropsychological measures and amyloid pathology. We identified rs13374761-A in SLAMF1 gene associated with less memory decline (MAF = 0.071, β= 0.0103, p = 4.14×10-8). Subgroup analysis showed stability of results across groups with different diagnosis at baseline. Rs13374761-A also had protective effects on global cognition (p = 0.024), episodic memory (p = 0.024), and semantic memory (p = 0.042), and exerts protection against a decrease in CSF Aβ42 concentration (p = 0.0463) and an increase in Aβ loading in cerebral cortex (p = 0.00666) among minor allele carriers. A novel variant in gene SLAMF1 affects the rate of memory decline in the aged population. Given the protective effect of this variant, SLAMF1 should be further investigated as a potential preventive and therapeutic target for monitoring cognition trajectories.

Vitamin D polygenic score is associated with neuroticism and the general psychopathology factor

Vitamin D, used here to refer to both 25-hydroxyvitamin D, the main circulating form of the vitamin, and 1,25-hydroxyvitamin D, the biologically active form, has been shown to influence brain development and function. Consistent with these findings, low levels of vitamin D have been implicated in various mental disorders, including depression, schizophrenia, and autism. Recently, a shared variance across multiple categories of mental health disorders has been identified and shown to be genetically influenced. This shared variance, thought to represent a general risk for psychopathology, has been termed the p factor. Individuals with high p factor scores are characterized by high neuroticism and low agreeableness and conscientiousness. Here, we investigated the links between vitamin D polygenic scores — derived from the latest genome-wide association study of circulating vitamin D (25-hydroxyvitamin D) levels — the Big Five personality traits (neuroticism, agreeableness, conscientiousness, openness-to-experience, and extraversion), and the p factor, in a sample of 522 (278 women, mean age 20 ± 1 years) non-Hispanic Caucasians. Vitamin D polygenic scores were significantly and negatively associated with neuroticism and the p factor, even after correcting for multiple comparisons, and controlling for sex, age, ancestry, socioeconomic status, and body mass index. Based on previous research implicating neuroticism as a risk factor for psychopathology, mediation was tested. Results showed a significant indirect effect from the vitamin D polygenic score to the p factor via neuroticism. Our findings support a genetic link between vitamin D levels, neuroticism, and the p factor, but due to the cross-sectional nature of our data, future studies are needed to clarify the causal associations between these phenotypes.

815 Outpatient Opioid Use in Burn Injuries Following Hospital Discharge: A Single Institution Evaluation

Abstract Introduction There is a growing concern regarding the unprecedented increase in morbidity and mortality related to the use of opioids. Prescription opioid abuse has been increasing dramatically in recent years. Prescription opioids have been shown to be favorable in perioperative management, however, their impact on chronic usage remains unclear. As an effort to help reduce opioid consumption following hospitalization for burn injuries, we look to evaluate the outpatient opioid consumption following hospital discharge at our institution. Methods After IRB approval, we obtained demographics, medical history, inpatient and outpatient opioid usage, treatment, and length of hospital stay of patients admitted with burn injuries who met study inclusion criteria (age ≥ 12 years and no history of opioid abuse prior to hospitalization) from January 1, 2011 to January 1, 2018. Data was analyzed using SAS v9.4. Results Our preliminary data included 210 patients with average age of 58 years, 75% non-Hispanic Caucasians and average total burn surface area of 18%. Medical histories observed included: hypertension (40%), diabetes (15%), hyperlipidemia (11%), depression (7%), and bipolar disorder (3%) among many others. 79% of patients had surgical intervention including excision and grafting, of which 32% had autografting procedures. All patients were treated with opioids during hospitalization, which included: fentanyl, hydromorphone, oxycodone-acetaminophen, morphine and oxycodone. 6% of patients had pain management consultation during hospitalization. 79% of patients were discharged with an opioid prescription, of which 21% had their opioid refilled during follow-up. There was no statistically significant difference in discharge opioid prescriptions (79% had surgical intervention versus 76% had no surgical intervention, p=0.69) and outpatient opioid prescription refills (17% had surgical intervention versus 17% had no surgical intervention, p=0.99) between patients who had surgical intervention for burn injuries versus those who did not. Conclusions This evaluation shows that there is no statistical difference in opioid usage between patients who had surgical intervention and those who did not for their burn injury treatments. Therefore, prescription opioids may not be necessary in postoperative care following hospital discharge. Applicability of Research to Practice With further research, we hope to evaluate the need for outpatient opioid prescriptions this treatment modality in effort of decreasing the order and use of opioids following hospital discharge in burn patients.

Safety of light emitting diode-red light on human skin: Two randomized controlled trials.

Therapeutic applications of light emitting diode-red light (LED-RL) are expanding, yet data on its clinical effects are lacking. Our goal was to evaluate the safety of high fluence LED-RL (≥160 J/cm2 ). In two phase I, single-blind, dose escalation, randomized controlled trials, healthy subjects received LED-RL or mock irradiation to the forearm thrice weekly for 3 weeks at fluences of 160-640 J/cm2 for all skin types (STARS 1, n = 60) and at 480-640 J/cm2 for non-Hispanic Caucasians (STARS 2, n = 55). The primary outcome was the incidence of adverse events (AEs). The maximum tolerated dose was the highest fluence that did not elicit predefined AEs. Dose-limiting AEs, including blistering and prolonged erythema, occurred at 480 J/cm2 in STARS 1 (n = 1) and 640 J/cm2 in STARS 2 (n = 2). AEs of transient erythema and hyperpigmentation were mild. No serious AEs occurred. We determined that LED-RL is safe up to 320 J/cm2 for skin of color and 480 J/cm2 for non-Hispanic Caucasian individuals. LED-RL may exert differential cutaneous effects depending on race and ethnicity, with darker skin being more photosensitive. These findings may guide future studies to evaluate the efficacy of LED-RL for the treatment of various diseases.

259. Racial Differences in Clinical Phenotype and Hospitalization of Blastomycosis Patients

BackgroundDimorphic fungal infections, such as blastomycosis, cause significant morbidity and mortality. Most studies describing blastomycosis have focused on non-Hispanic Caucasians and our understanding of the clinical presentation and outcomes for patients of other race/ethnicities is limited. We evaluated whether clinical presentation and disease severity varied across racial/ethnic groups.MethodsBlastomycosis patients were identified from Marshfield Clinic Health System and patient data were abstracted from electronic medical records. Blastomyces genotyping was performed for cases with available isolates. Univariate analyses using χ 2 tests and multivariate logistic regression modeling were used to determine the association of race/ethnicity with clinical presentation. Significance was defined as P ≤ 0.05.ResultsIn total 477 patients were included.Age differences were observed across race/ethnicity categories (P < 0.0001). Non-Hispanic, Caucasians were oldest (47 years, SD 20) and Asians were the youngest (30 years, SD 18). Underlying medical conditions were more common in non-Hispanic Caucasians (55%) and African Americans (AA) (52%) than Hispanic Caucasians (27%) and Asians (29%, P = 0.0002). Risk for hospitalization was highest for Hispanic Caucasian (aOR 2.9, 95% CI 1.2–1.7), American Indian Alaskan Native (AIAN) (aOR = 2.4; 95% CI 1.0–5.5), and Asian (aOR = 1.9; 95% CI 1.0–3.6) patients when compared with non-Hispanic Caucasian patients. Ninety percent of B. dermatitidis infections occurred in non-Hispanic Caucasians whereas blastomycosis in Hispanic Caucasian, AIAN, and Asian patients was frequently caused by B. gilchristii (P < 0.0001).ConclusionHispanic Caucasian, AIAN, and Asian blastomycosis patients were younger and healthier, but more frequently hospitalized. Patients in these racial/ethnic groups may need more aggressive treatment and closer therapeutic monitoring. Underlying host factors along with organism virulence likely play a role in these differences.Disclosures All authors: No reported disclosures.