Multiethnic Population Research Articles

Genotype-phenotype associations in paragangliomas of the temporal bone in a multi-ethnic cohort

Background Temporal bone paragangliomas are rare tumours with variable presentation that can be hereditary. Identification of clinical and genetic factors of aggressive tumour behaviour is important. Objective To determine the underlying genetic mutations and genotype/phenotype correlations in a multi-ethnic population of South Florida with sporadic temporal bone paragangliomas. Methods In a cohort of glomus tympanicum (GT) and glomus jugulare (GJ) cases, we assessed the frequency of pathogenic single nucleotide variants, insertions, deletions, and duplications in coding exons of genes that have been associated with paragangliomas (SDHB, SDHC, SDHD, SDHA, SDHAF2, RET, NF1, VHL, TMEM127, and MAX). Results None of the 12 GT cases had mutations. Among 13 GJ cases, we identified four mutation carriers (31%); two in SDHC, one in SDHB, and one in SDHD. All patients with pathogenic mutations were of Hispanic ethnicity, presented at a younger age (mean 27.5 versus 52.11 years), and with more advanced disease when compared to mutation-negative GJ cases. Conclusions and Significance: Mutations in the SDH genes are found in 31% of sporadic GJ. SDH-associated GJ had advanced disease and a 50% risk of metastasis. Our data supports emerging recommendations for genetic screening in all populations with GJ tumours as the genetic status informs management.

Asian (Bio)Values: Constructing Asian Difference and Biovalue in the Singapore Diabetes Discourse

Existing studies demonstrate how biomedical researchers construct multiethnic populations as biovaluable. A multiethnic population with a diverse gene pool allows for the scaling of disease research and treatments to other countries. This “fact” serves an important role to attract investments in the national bioscientific sector. Yet these studies do not describe how such promissory narratives are translated for public consumption, an important step given how science policy requires public buy-in. My research asks how the relationship between Singapore and Asia is constructed as biovaluable through the media. Examining the media discourse on diabetes in Singapore, I find that the construction of biovalue in the media (1) relies on emotional and pragmatic appeals to Asian inclusivity in scientific research, (2) highlights biological Asian difference and market opportunities based on scaling, and (3) enacts the connection between Singapore and Asia in a distorted manner where ethnic minorities are sometimes excluded. This research builds on the existing literature on the political economy of the biosciences through examining the intersection between science policy, public health, race and ethnicity, and scientific communication in postcolonial nations such as Singapore, where the media plays an authoritative role in communicating scientific information to the public.

963-P: Near-Infrared Device for Diabetes Screening—ANODE01 Study

Background: Diabetes mellitus (DM) screening is currently complex, inefficient and requires resource-intensive, invasive sampling. Development of affordable, rapid, and precise mass-screening tools is valuable in identifying the millions with undiagnosed DM, especially in lower income countries. Materials and Methods: Accuracy and safety of a novel miniaturized full-spectrum near-infrared (NIR) spectroscopy device intended for DM screening was assessed in a multi-ethnic population with (n=50) or without (n=50) DM. Thirty NIR spectra scans per each middle fingernail and hand were tested for detection of dichotomised DM status based on cut-off values (< HbA1c 6.5% or 6.0 ≥) and specificity (%) of chemometrics outcomes, in assessment of glycated nail keratin versus an HbA1c point-of-care assay as control. Results: The cohort had mean age of 43.6 vs 64.4 years, 42 vs 76% females and 54 vs 68% Caucasians for non-DM and DM participants. Median (IQR) HbA1c % was 5.45 (5.2 - 5.6) and 6.8 (6.3-7.6), respectively. Clinical feasibility for NIR use was confirmed with no adverse device -related events reports for the over 6000 spectral measurements. The NIR-device demonstrated a specificity of 95.2% and 94.1% at HbA1c 6.5 and 6.0% cut-off levels, respectively (Table). Conclusions: Our preliminary results indicate high specificity and potential for clinical implementation of non-invasive NIR technology in detection of those without immediate DM risk. Disclosure P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. D.Lazaro-pacheco: Consultant; Glyconics Ltd. J.E.Salter: None. P.M.Paldanius: Consultant; Glyconics Ltd, Speaker's Bureau; Novartis. Funding Glyconics

179-LB: Should We Screen with a Fasting Blood Glucose Test? A Novel Two-Step Screening Strategy for Gestational Diabetes—A Large Tertiary Comparative Cohort Study

Background: Gestational diabetes mellitus (GDM) diagnosis is resource intensive and controversial. A modified COVID-19 GDM diagnostic method was introduced at Western Health Melbourne, an Australian tertiary hospital caring for a multi-ethnic population with a high GDM prevalence at 20-23%. In place of a universal 2 hour 75g OGTT, a novel two step diagnostic method was instituted. A fasting blood glucose (FBG) was performed with thresholds based on a secondary analysis of HAPO data. A FBG of ≥5.1mmol/L (91.8mg/dL) diagnosed GDM; women with FBG 4.7-5.0mmol/L (84.6-90.0mg/dL) proceeded to an OGTT (IADPSG diagnostic criteria); FBG ≤4.6mmol/L (82.8mg/dL) was considered to exclude GDM. Methods: A retrospective cohort study of singleton pregnancies birthing after 20 weeks’ gestation compared perinatal outcomes in 6469 women who underwent modified screening (MS) during the COVID-19 pandemic with 8669 women who had conventional screening (CS) prior to COVID-19. Results: GDM prevalence was the same using either MS or CS (22.9 vs 22.2% p=0.31) with similar rates of insulin use. There was no difference in the prevalence of large for gestational age infants (10.3 vs 9.4% p=0.06), pre-term birth (6.6 vs 6.4% p=0.53) or gestational age at birth (39.2 vs 39.1 weeks). Mean birth weight was increased with MS (3335g vs 3307g) and small for gestational age rate reduced (9.1 vs 10.5% p=0.01). The MS group had fewer inductions (34.2 vs 39.8% p<0.01). Primary caesarean section rate was unchanged (18.4 vs 18.4% p=0.91). MS reduced the need for an OGTT by 76%. Women with a FBG ≤4.6mmol/L by MS had non-inferior outcomes compared to women with a FBG ≤4.6mmol/L with CS irrespective of GDM diagnosis. Conclusion: In a large multi-ethnic cohort with a high prevalence of GDM, modified screening using FBG greatly reduced the number of resource intensive OGTTs with non-inferior perinatal outcomes. A prospective randomised trial comparing these methods is warranted. Disclosure J. Deitch: None. J. M. Said: None. G. R. Teale: None. D. Kevat: Advisory Panel; Novo Nordisk, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Novo Nordisk, Abbott Diabetes, AstraZeneca. I. Lee: None. C. J. Yates: None. E. Kathpal: None. P. Lawton: None. I. Shahid: None. C. Steele: None. P. S. Hamblin: None. B. Krishnamurthy: None. Funding Australian Government Research Training Program; Sheppard Millar Lowe Research Trust Scholarship

Kidney Function and Long-Term Risk of End-Stage Kidney Disease and Mortality in a Multiethnic Population

Contemporary differences between South Asian and White ethnicities in the incidence of end-stage kidney disease (ESKD) and mortality are poorly described. Data for all South Asian patients who had an estimated glomerular filtration rate (eGFR) measure after January 1, 2006, and 1 million randomly selected participants of other ethnicities were extracted from the Clinical Practice Research Datalink (CPRD). All participants were followed-up with from index date until ESKD, all-cause mortality, or end of study. All-cause mortality rate and ESKD incidence rate by age were described among Whites and South Asians, and adjusted hazard ratios (HRs) of these 2 outcomes by baseline eGFR estimated using Cox proportional hazard model. A total of 40,888 South Asians and 236,634 Whites were followed for a median of 5.3 and 9.4 years for ESKD incidence and mortality outcomes, respectively. All-cause mortality rates were higher among Whites than South Asians; South Asian women aged between 70 and 85 years had a slightly higher ESKD incidence rate compared to their White counterparts. Compared to Whites with a baseline eGFR of 90 ml/min per 1.73 m2, adjusted HRs for all-cause mortality were significantly lower among South Asians than Whites; however, adjusted HRs for ESKD incidence by baseline eGFR were similar in both ethnicities. Calculating South Asian eGFRs using an ethnicity-specific equation had no impact on the results. South Asians experience lower mortality than Whites but not substantially higher rates of ESKD. Further research is warranted to better understand the reasons for these ethnic differences and possible impacts on chronic kidney disease (CKD) service delivery and patient outcomes.

Birth characteristics and risk of Ewing sarcoma

PurposeThe incidence of Ewing sarcoma varies according to race and ethnicity, and genetic susceptibility is known to affect disease risk. Apart from these factors, the etiology of Ewing sarcoma is largely unknown.MethodsWe compared the birth characteristics of a population-based series of 556 Ewing sarcoma cases born in California in 1978–2015 and diagnosed in 1988–2015 with those of 27,800 controls selected from statewide birth records and frequency-matched to cases on the year of birth, using multivariable logistic regression models. We also assessed whether Ewing sarcoma clustered within families.ResultsCompared to non-Hispanic White subjects, Black (odds ratio [OR] = 0.07, 95% confidence interval [CI] 0.03–0.18), Asian (OR = 0.57, 95% CI 0.41–0.80), and Hispanic (OR = 0.73, 95% CI 0.62–0.88) individuals had a significantly lower risk of Ewing sarcoma. Race and ethnicity differences were more profound for metastatic Ewing sarcoma. Birthweight was also identified as a significant risk factor (OR = 1.09, 95% CI 1.00–1.18 for each 500 g increase in birthweight). A separate family-based cancer clustering analysis did not suggest any strong role for familial predisposition alleles.ConclusionsThis population-based study with minimal selection bias provides support for a role of accelerated fetal growth in the etiology of Ewing sarcoma in addition to more precise estimates of racial and ethnic variations in disease risk. This comparatively large analysis of birth characteristics and Ewing sarcoma in a multiethnic population should stimulate further investigations into genetic and environmental causes.

Bordering Ladakh, Again: From Ecological Flows to Cartographic Competition

ABSTRACT In August 2019, the Indian government dissolved the state of Jammu and Kashmir, designating its Northern region as the Union Territory of Ladakh. Two months later, it released a new Political Map of India on which Ladakh was drawn as one of India’s largest territories. Like most representations of territory on political maps, the claims made were simplified. India’s rendering did not acknowledge that Pakistan and China administered much of Ladakh’s territory; nor did it represent the region’s intricate, multi-ethnic population, topography, or ecosystems. This article approaches the construction of this political map historically. Rather than using regional history to bolster any state’s claims, we argue that the confusion over the map reflects a disconnect between the abstractions of state territory and the realities of high-altitude socio-ecologies. We compare the socio-ecologically and climatically embedded bordering practices of pre-territorial Tibetan–Ladakhi states outlined in local language sources with the abstract understanding of territorialised borders that the new map represents. The Tibetan–Ladakhi approach, which concentrated on pathways and mountain-pass checkpoints, allowed for social and ecological flows around and through these checkpoints. By contrast, the current bordering regimes have bifurcated communities, demanded fixedness, and required three large armies to defend arbitrary borders.

#5228 ASSESSING ACCURACY OF POINT-OF-CARE CREATININE AND POTASSIUM TESTING IN A MULTI-ETHNIC SOUTH LONDON POPULATION

Abstract Background and Aims Point-of-care (POC) testing allows rapid analysis of blood samples without delay of laboratory testing. For patients with chronic kidney disease (CKD), this allows for instant identification of changes in kidney function, such as acute kidney injury or hyperkalaemia, and assists in timely decision-making in outpatient or community settings (e.g. commencing or up-titrating medications dependent on renal function). It also provides an opportunity for early recognition of CKD in high-risk populations by providing screening in more convenient and trusted settings. To achieve these aims, it essential to confirm that POC systems can produce accurate results in real world settings with diverse patient populations. This pilot validation study assessed accuracy of the Siemens Epoc Blood Analysis System venous creatinine and potassium compared with laboratory assays in a diverse UK renal patient population. Method Venous blood samples from 57 patients, aged ≥ 18 years old and receiving care at a London teaching hospital, were analysed using the Siemens Epoc Blood Analysis System. POC-Creatinine (POC-Cr) and Potassium (POC-K) measurements were compared with laboratory (IDMS-traceable Siemens enzymatic and Roche) assays. Demographics (age, ethnicity and sex) were recorded for each patient. Passing-Bablock regression analysis were used to compare the results using both methods. Comparison between testing methods was assessed using a Bland-Altman plot. Limits of agreement were compared with CLIA criteria for acceptable performance for creatinine and potassium. Results The mean age was 55.6 ± 15.3 years old and 64.9% were male (n = 37). The majority of patients were of White (N = 23; 40.4%), Black (N = 21; 36.8%) or South Asian (N = 9; 15.8%) ethnicity respectively. Median POC-Cr was 216 μmol/L (interquartile range (IQR) 111, 396 μmol/L) versus median venous creatinine 212 μmol/L (IQR 114, 380 μmol/L). The median bias for creatinine was +1.0 (IQR -3.0, +8.0). Limits of agreement on Bland-Altman plot were +36.5μmol/L and – 34.4μmol/L (Figure 1). Overall, there remained a strong positive correlation between POC-Cr and IDMS-traceable enzymatic creatinine assays (R = 0.997; P<0.0001) (Figure 2). Median POC-K was 4.3 mmol/L, IQR 4.0, 4.8 mmol/L versus median venous potassium 5.0, IQR 4.3, 5.3 mmol/L. The median bias for potassium was +0.4 (IQR +0.2, +0.5). Limits of agreement on Bland-Altman plot were +0.16mmol/L and – 0.91mmol/L (Figure 3). A strong positive correlation between POC-K and laboratory potassium assays was also confimed (R = 0.937; P<0.0001) (Figure 4). Conclusion There was strong positive correlation between POC and laboratory analysis of venous creatinine, comparable to product literature (R = 0.997 vs 0.998). Limits of agreement were outside the CLIA criteria for acceptable performance (+/- 27μmol/L). POC and laboratory potassium levels were also strongly correlated and comparable to product literature (R = 0.937 vs 0.997). Limits of agreement were outside the CLIA criteria for acceptable performance (+/- 0.5mmol/L). This discrepancy is likely due to haemolysis in some blood samples and small sample size. Overall, this pilot study demonstrated a strong correlation between POC and laboratory testing. Larger scale evaluation is still required in a multi-ethnic population, prior to assessing feasibility in community-led protocolized pathways.

Literati of the Garrisons

Conventionally characterized as a perfunctory exercise established to bolster the ranks of Manchu officials, the Qing dynasty civil service translation examination, and its accompanying curriculum of literary and classical training, played a major role in the development of literary-intellectual values among members of the Eight Banners. This article demonstrates how it contributed to the emergence of a multiethnic population of Manchu, Mongol, and Chinese bannermen possessing high levels of Manchu literacy who would become consumers and producers of Manchu literature, translations, and textbooks, engendering a literati culture that extended beyond the administrative concerns of the court. While the Manchu language is commonly considered to have become moribund by the late eighteenth century, the translation examination highlights its continued, and in certain contexts growing, significance into the early twentieth century. These findings require a reexamination of Manchu cultural identity beyond imperial ideology and the role of non-Han peoples in literati culture more broadly. They also provide new insights into the classicizing potential of vernacular languages within the linguistic ecologies of early modern East Asia.

Risk Factors of Secondary Cardiovascular Events in a Multi-Ethnic Asian Population with Acute Myocardial Infarction: A Retrospective Cohort Study from Malaysia.

This retrospective cohort study investigated the incidence and risk factors of major adverse cardiovascular events (MACE) after 1 year of first-documented myocardial infarctions (MIs) in a multi-ethnic Asian population. Secondary MACE were observed in 231 (14.3%) individuals, including 92 (5.7%) cardiovascular-related deaths. Both histories of hypertension and diabetes were associated with secondary MACE after adjustment for age, sex, and ethnicity (HR 1.60 [95%CI 1.22-2.12] and 1.46 [95%CI 1.09-1.97], respectively). With further adjustments for traditional risk factors, individuals with conduction disturbances demonstrated higher risks of MACE: new left-bundle branch block (HR 2.86 [95%CI 1.15-6.55]), right-bundle branch block (HR 2.09 [95%CI 1.02-4.29]), and second-degree heart block (HR 2.45 [95%CI 0.59-10.16]). These associations were broadly similar across different age, sex, and ethnicity groups, although somewhat greater for history of hypertension and BMI among women versus men, for HbA1c control in individuals aged >50 years, and for LVEF ≤ 40% in those with Indian versus Chinese or Bumiputera ethnicities. Several traditional and cardiac risk factors are associated with a higher risk of secondary major adverse cardiovascular events. In addition to hypertension and diabetes, the identification of conduction disturbances in individuals with first-onset MI may be useful for the risk stratification of high-risk individuals.

Genome-wide Association Study for AKI.

While common genetic risks for chronic kidney disease are well established, genetic factors influencing risk for acute kidney injury (AKI) in hospitalized patients are poorly understood. We conducted a genome-wide association study in 1,369 participants in the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) Study; a multi-ethnic population of hospitalized participants with and without AKI matched on demographics, comorbidities and kidney function prior to hospitalization. We then completed functional annotation of top-performing variants for AKI using single cell RNA sequencing data from kidney biopsies in 12 AKI patients and 18 healthy living donors from the Kidney Precision Medicine Project (KPMP). No genome-wide significant associations with AKI risk were found in ASSESS-AKI (p < 5 x 10-8 ). The top two variants with the strongest association with AKI mapped to the dispatched RND transporter family member 1 (DISP1) gene and toll like receptor 5 (TLR5) gene locus, rs17538288 (OR=1.55, 95% CI:1.32-182, p=9.47 x 10-8 ) and rs7546189 (OR=1.53, 95% CI:1.30-1.81, p=4.60 x 10-7 ). In comparison to kidney tissue from healthy living donors, kidney biopsies in patients with AKI showed differential DISP1 expression in proximal tubular epithelial cells (adjusted p=3.9 x 10 -2 ) and thick ascending limb of the loop of Henle (TAL) (adjusted p =8.7 x 10 -3 ) and differential TLR5 gene expression in TAL (adjusted p =4.9 x 10 -30 ). AKI is a heterogeneous clinical syndrome with various underlying risk factors, etiologies and pathophysiology that may limit the identification of genetic variants. While no variants reached genome wide significance, we report two variants in the intergenic region between DISP1 and TLR5 , suggesting this region as a novel risk for AKI susceptibility.

Particulate matter, traffic-related air pollutants, and circulating C-reactive protein levels: The Multiethnic Cohort Study

Inhaled particles and gases can harm health by promoting chronic inflammation in the body. Few studies have investigated the relationship between outdoor air pollution and inflammation by race and ethnicity, socioeconomic status, and lifestyle risk factors. We examined associations of particulate matter (PM) and other markers of traffic-related air pollution with circulating levels of C-reactive protein (CRP), a biomarker of systemic inflammation. CRP was measured from blood samples obtained in 1994–2016 from 7,860 California residents participating in the Multiethnic Cohort (MEC) Study. Exposure to PM (aerodynamic diameter ≤2.5 μm [PM2.5], ≤10 μm [PM10], and between 2.5 and 10 μm [PM10-2.5]), nitrogen oxides (NOx, including nitrogen dioxide [NO2]), carbon monoxide (CO), ground-level ozone (O3), and benzene averaged over one or twelve months before blood draw were estimated based on participants’ addresses. Percent change in geometric mean CRP levels and 95% confidence intervals (CI) per standard concentration increase of each pollutant were estimated using multivariable generalized linear regression. Among 4,305 females (55%) and 3,555 males (45%) (mean age 68.1 [SD 7.5] years at blood draw), CRP levels increased with 12-month exposure to PM10 (11.0%, 95% CI: 4.2%, 18.2% per 10 μg/m3), PM10-2.5 (12.4%, 95% CI: 1.4%, 24.5% per 10 μg/m3), NOx (10.4%, 95% CI: 2.2%, 19.2% per 50 ppb), and benzene (2.9%, 95% CI: 1.1%, 4.6% per 1 ppb). In subgroup analyses, these associations were observed in Latino participants, those who lived in low socioeconomic neighborhoods, overweight or obese participants, and never or former smokers. No consistent patterns were found for 1-month pollutant exposures. This investigation identified associations of primarily traffic-related air pollutants, including PM, NOx, and benzene, with CRP in a multiethnic population. The diversity of the MEC across demographic, socioeconomic, and lifestyle factors allowed us to explore the generalizability of the effects of air pollution on inflammation across subgroups.

ASSOCIATION BETWEEN SYSTOLIC BLOOD PRESSURE AND CHANGE IN EGFR OVER TIME IN A MULTI-ETHNIC COHORT: THE HELIUS STUDY

Objective: The assess the extent to which blood pressure relates to progression of CKD, among different ethnicities with disparate cardiorenal risk. We assessed the relationship between baseline systolic blood pressure (SBP) and change in renal function over time in a multi-ethnic population. Design and method: This analysis used baseline and follow-up data from 9 828 participants in the prospective Healthy Life in an Urban Setting (HELIUS) cohort study, a population-based study, including individuals of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan descent. Linear regression and interaction analysis were used to assess the association between baseline SBP and change in eGFR over time. Results: Overall eGFR decreased by -0.30 ml/min/1.73m2 (95%CI[-0.42, -0.19], p&lt;0.001) per 10 mmHg increase in baseline SBP after 6.3 (SD 1.1) years of follow-up. This curve steepened from a SBP of 120 mmHg onwards to -0.44 ml/min/1.73m2 (95%CI[-0.61, -0.27], p&lt;0.001) for every 10 mmHg increase in SBP. The association was significantly influenced by ethnicity (p&lt;0.001), diabetes (p = 0.003) and albuminuria (p = 0.002), but not by age or sex. Individuals with albuminuria or diabetes had a more than 3 times larger SBP related eGFR decline compared to those without diabetes or albuminuria. Dutch, African Surinamese and Moroccan participants had a slightly steeper eGFR decline, but the direction of effect was consistent across all subgroups. Conclusions: Our findings confirm the relation between SBP and eGFR over time in different ethnic groups, steepening from a SBP of 120 mmHg onwards and may help to further guide strategies for preventing hypertension related CKD.

Impacts of cerebral small vessel disease on global and domain‐specific cognition

AbstractBackgroundThe 2021 Alzheimer’s Association International Conference press release forecasted global dementia cases to triple by 2050, due to the major contribution of increases in vascular risk factors. The Global Vascular Risk Score (GVRS) was developed to predict vascular events using a point‐based index for risk factor variables, though has demonstrated to be a significant predictor of global and domain‐specific cognitive performance in a multi‐ethnic cohort (Rundek, T. et al. Global Vascular Risk Score and CAIDE Dementia Risk Score Predict Cognitive Function in the Northern Manhattan Study. J Alzheimers Dis 73, 1221‐1231 (2020)). However, more than half of the variance in global and domain‐specific cognitive performance is still unexplained by GVRS variables. We sought to explain additional variance in cognitive performance by addition of MRI biomarkers of cerebral small vessel disease to the GVRS model.MethodWe included 1290 subjects from the multiethnic Northern Manhattan Study population (age 64+/‐8 years, 40% women, 66% Hispanic, 17% non‐Hispanic Black, 15% non‐Hispanic White, education 10+/‐5 years). Multivariate linear regression models were employed to assess the added value of the cerebral small vessel disease MRI measures (white matter hyperintensity volume, silent brain infarcts, cerebral microbleeds, and perivascular spaces) beyond GVRS variables in explaining more variance in global and domain‐specific (episodic memory, executive function, semantic memory, and processing speed) cognitive performance. The explained variance (R2) of the GVRS model was compared to the proposed model with added imaging markers to determine their predictive performance. Statistical significance was determined using F‐statistic difference test between the models.ResultThe explained variance (R2) and F‐statistic for models of global and domain‐specific cognition are in the table. Addition of MRI measures significantly improved the model for global cognition (F(4, 1108) = 2.68, p &lt; 0.05) and domain‐specific cognitive performance models of episodic memory (F(4, 1096) = 3.34, p &lt; 0.01) and processing speed (F(4, 1096) = 2.40, p &lt; 0.05).ConclusionMRI measures of cerebral small vessel disease explain more variance in global cognition, episodic memory, and processing speed than GVRS factors alone. However, most of the variance in cognitive performance remains unexplained.

Neurocognitive Disorders in HIV-positive Patients.

(1) To know the prevalence of HAND in HIV-infected patients of a multi-ethnic population. (2) To describe various types of neurocognitive impairment among patients of HAND and study the factors affecting HAND. This study was a cross-sectional descriptive study conducted on 250 HIV-positive patients in outpatient department (OPD) of a tertiary care center in Mumbai, conducted over a period of 12 months. Patients with HIV-1 attending the OPD and having a minimal formal education of 4 years were included. Patients with concomitant delirium, any known central nervous system (CNS) disorder, any psychiatric disorder, and pregnant females were excluded. Outcome measures-the test batteries used were (1) International HIV Dementia Scale (IHDS) and (2) Addenbrookes cognitive examination-revised (ACE-R) scale. Of 250 subjects studied, 55.6% (139) were males and 44.4 % (111) were females. The mean age of study population was 39.42 years. The mean years of education were 8.32 years. The mean duration of infection (diagnosis of HIV-positive state) was 64.49 months and the mean duration of HAART intake in our patients was 52.30 months. The mean cluster of differentiation 4 (CD4) counts of our subjects were 527.13 per cumm [standard deviation (SD) of 234.13]. The mean nadir CD4 counts were 224.35 per cumm (SD of 115.09). Using the ACE-R scale, the prevalence of HAND was 71.60%, of which 37.20% had an asymptomatic neurological impairment, 29.60% had mild cognitive dysfunction, and 4.80% had HAD. Memory, verbal fluency and visuospatial abilities were the most affected domains on the ACE-R and memory recall and psychomotor speed were affected more on the IHDS. The prevalence of HAND was more with increasing age (p = 0.020), lesser education (p &lt; 0.00) and lesser nadir CD4 counts (p &lt; 0.00). However, it was not affected by the duration of the disease and the current CD4 counts (p &gt; 0.05). Human immunodeficiency viruses (HIV) associated neurocognitive disorders HAND is common in HIV-positive patients, most of whom are asymptomatic. Older patients with less education and severe disease, having lower nadir counts are at the highest risk of HAND. Memory, verbal fluency, and visuospatial abilities were the most commonly affected domains.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort

Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. This research was supported by theNUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131).The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations

Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.

Development of a calculated panel reactive antibody calculator for the United Arab Emirates: a proof of concept study

Calculated panel reactive antibody (CPRA) is used to help increase sensitized patient’s access to transplantation. United Arab Emirates (UAE) has a diverse resident population hence we developed a UAE–CPRA calculator based on HLA antigen frequencies of the different ethnic groups that represent the UAE population. HLA antigen frequencies at serological split antigen level for HLA-A, -B, -C, -DRB1 and -DQB1 of 1002 healthy unrelated donors were performed. We subsequently compared the performance of the UAE CPRA calculator with the Organ Procurement and Transplantation Network (OPTN) and the Canadian CPRA calculators in 110 Kidney Transplant waitlist patients from January 2016 to December 2018. Lin’s concordance correlation coefficient showed a moderate agreement between the UAE and OPTN calculator (Rc = 0.949, 95% CI 0.929–0.963) and the UAE and Canadian calculators (Rc = 0.952, 95% CI 0.932–0.965). While there continued to be a moderate agreement (Rc = 0.937, UAE versus OPTN calculator) in the lower sensitized group, a poor agreement (Rc = 0.555, UAE versus OPTN calculator) was observed in the higher sensitized group. In this study, we provide a template for countries to develop their own population-specific CPRA calculator. Implementation of the CPRA algorithm based on HLA frequencies of the multi-ethnic UAE population will be more fitting to increase access to transplantation and improve transplant outcomes. Our study demonstrates that the CPRA calculators developed using the data from the western population had poor correlation in our higher sensitized patients disadvantaging them in potential organ allocations systems. We plan to further refine this calculator by using high resolution HLA typing to address the problem of a genetically diverse population.

(350) Narcotic Requirements and Operative Outcomes of a Pudendal Nerve Block Prior to Primary Inflatable Penile Prosthesis Implantation in a Multiethnic Population

Abstract Introduction There are various analgesic regimens for post-operative pain control following inflatable penile prosthesis (IPP) implantation. Specifically, post-operative pain control with opioids is a common practice, but efforts to minimize narcotic usage are vital given the current opioid epidemic in the United States. Pudendal nerve block (PNB) provides regional perineal and penile anesthesia and represents an attractive option to maximize pain control while minimizing post-operative narcotic use. However, there is a paucity of studies describing whether utilization of PNBs decreases intra- and post-operative narcotic requirements following IPP implantation. Objective To determine whether PNB utilization in a multiethnic population undergoing primary IPP implantation can decrease rates of post-operative opiate usage. Secondary objectives were to assess PNB utilization on intra-operative and 30-day safety outcomes. Methods A single institution retrospective study was conducted of patients who underwent primary IPP implantation between December 2015 and February 2022. Demographic data, intra-operative characteristics, and outcome measures were extracted from electronic medical records. Baseline characteristics of PNB (yes or no) were summarized and analyzed using a Student’s t-test, Chi-square test, or Mann-Whitney U for non-normally distributed variables. PNB usage and PACU opioid administration (yes or no) were analyzed using binary logistic regression for univariate and multivariate analysis. Results A total of 363 patients were included, 294 (81.0%) in the PNB group and 69 (19.0%) in the non-PNB group. The majority of patients were of Hispanic race (62.3%). History of chronic pain (17.7% vs. 7.2%, p=0.03) and hyperlipidemia (52.0% vs. 34.8%, p=0.01) were more prevalent in the PNB group. Significantly more IPPs in the PNB group had cylinders measuring 20 centimeters or greater (57.1% vs 41.2, p=0.017). Estimated blood loss of 50ml or greater (43.1% vs. 20.0%, p&amp;lt;0.001), PACU narcotic usage (61.6% vs. 75.4%, p=0.040) and time (minutes) spent in the PACU (144 [111-185] vs. 238 [162-307], p&amp;lt;0.001) were all significantly lower in the PNB group. There were no significant differences in postoperative and 30-day safety outcomes. On univariate analysis, both PNB (OR=0.52, p=0.043) and age above 65 (OR=0.53, p=0.004) were associated with a lower likelihood of receiving opiates in the PACU, while only age remained significant (OR=0.53, p=0.006) on multivariate analysis. Conclusions Pre-operative PNB decreases intra-operative estimated blood loss, post-operative opioid analgesic requirements and time spent in PACU in patients undergoing a primary IPP implantation. Thus, PBN represents a potentially attractive, non-opioid means of analgesia in patients undergoing primary IPP surgery. Disclosure No

(288) Risk Factors and Real-World Short-Term Outcomes of a Failed Trial of Void After Rezum in a Multiethnic Population

Abstract Introduction A failed trial of void (TOV) following surgery for benign prostatic hyperplasia (BPH) predisposes patients to have trouble voiding, increases hospital stays and office visits, and increases detrusor muscle injury due to bladder over-distention. Rezum is a minimally invasive surgical therapy that utilizes convective radiofrequency water vapor thermal energy to ablate obstructive lobes of the prostate, resulting in improvement in lower urinary tract symptoms (LUTS) secondary to BPH. Identifying risk factors for a failed Rezum TOV can help identify a group of BPH patients who may need to be counseled preoperatively for an increased risk of postoperative urinary retention and therefore have their period of postoperative catheterization extended. Objective The purpose of the study was to identify risk factors for a TOV following Rezum and assess the impact of a failed TOV on real-world short-term outcomes. Methods A single office, retrospective study was conducted on patients treated with Rezum between December 2017 and October 2019. Patients were included if they had a follow-up for catheter removal after Rezum. Patients were excluded if they were in urinary retention requiring catheterization on the day of the procedure. A urinary catheter was placed in all patients following treatment. Demographic data and outcome measures, including International Prostate Symptom Score (IPSS), quality of life (QoL), International Index of Erectile Function (IIEF)-Erectile and -Orgasmic function, maximum urinary flow rate (Qmax), postvoid residual (PVR), and adverse events were analyzed at baseline, 1-, 3-, and/or 6-months postoperatively. Risk factors were identified through multivariate logistic regression analyses. Results A total of 289 patients were included, with the majority being Asian (36.0%), followed by non-Hispanic Black (28.7%), Hispanic (22.5%), and non-Hispanic White (12.8%). Thirty-five patients (12.1%) failed their TOV while 254 (87.9%) had a successful TOV. All patients were given a TOV after a median of 5 days (4-5). Those who failed their TOV spent a mean of 13.7 days (SD: 13.3) with a catheter. Patients who failed their TOV were more likely to get a urinary tract infection (20.0% vs. 4.7%, p 200 ml failed their TOV (40.0%) when compared to patients with a baseline PVR &amp;lt;200 ml (10.9%, p=0.008). Conclusions Following Rezum, approximately 1 in 8 patients were not able to pass their initial TOV. Baseline PVR was the only independent risk factor for a failed TOV. Nevertheless, all patients experienced significant relief in LUTS with preservation of sexual function. Patients with large baseline PVR, particularly &amp;gt;200 ml, should be counseled on possibly failing their TOV and requiring a catheter for an extended period. These patients should also be counseled on alternative BPH treatment options for which they may be a better candidate for. Disclosure No