Multiracial Cohort Research Articles

OUTCOMES OF INTRAVESICAL BACILLUS CALMETTE-GUERIN IN A MULTIRACIAL COHORT WITH NON-MUSCLE-INVASIVE BLADDER CANCER.

We sought to determine if outcomes of Bacillus Calmette-Guerin (BCG) therapy in patients with non-muscle-invasive bladder cancer (NMIBC) vary by race. A retrospective chart review was conducted on 149 patients treated with BCG for intermediate- and high-risk NMIBC between 2001 and 2018, and who were followed up for cancer recurrence through March 2019.The primary outcomes were disease-free survival (DFS), low-grade disease-free survival (LGDFS), high-grade disease-free survival (HGDFS), and progression-free survival (PFS) at five years. Kaplan-Meier survival curves stratified by race (African American vs non-African American) were analyzed for all the above outcomes and multivariate Cox regression analyses were also performed to compare recurrence differences by race, after adjusting for age, sex, initial stage and grade. Of the 149 patients, 37.6% were Caucasian, 24.8% were African American, 26.8% were Hispanic, and 10.7% were of other/unknown race. Disease stage at initial presentation was 65.1% Ta, 34.9% T1, and 18.1% CIS. African American patients (N=37) did not have evidence for worse outcomes compared to non-African American patients when considering DFS (54.1% vs. 65.7%, p = 0.202), HGDFS (58.8% vs. 71.7%, p = 0.158), and PFS (83.8% vs. 92.6%, p = 0.117) at five years. Multivariate analysis did not reveal statistically significant racial differences in recurrence or progression. African Americans with NMIBC did not have worse disease recurrence and progression after receiving intravesical BCG treatment. Although there did appear to be a trend towards worse oncologic outcomes in African Americans, larger studies are needed to validate this finding.

Reported Neighborhood Traffic and the Odds of Asthma/Asthma-Like Symptoms: A Cross-Sectional Analysis of a Multi-Racial Cohort of Children.

Asthma in children poses a significant clinical and public health burden. We examined the association between reported neighborhood traffic (a proxy for traffic-related air pollution) and asthma among 855 multi-racial children aged 4–8 years old who participated in the Environmental Influences on Child Health Outcomes (ECHO) cohort. We hypothesized that high neighborhood traffic density would be associated with the prevalence of asthma. Asthma/asthma-like symptoms (defined as current and/or past physician diagnosed asthma, past wheezing, or nighttime cough or wheezing in the past 12 months) was assessed by parental report. The relationship between neighborhood traffic and asthma/asthma-like symptoms was assessed using logistic regression. The prevalence of asthma/asthma-like symptoms among study participants was 23%, and 15% had high neighborhood traffic. Children with significant neighborhood traffic had a higher odds of having asthma/asthma-like symptoms than children without neighborhood traffic [adjusted OR = 2.01 (95% CI: 1.12, 3.62)] after controlling for child’s race-ethnicity, age, sex, maternal education, family history of asthma, play equipment in the home environment, public parks, obesity and prescribed asthma medication. Further characterization of neighborhood traffic is needed since many children live near high traffic zones and significant racial/ethnic disparities exist.

Effects of housing value and medical subsidy on treatment and outcomes of breast cancer patients in Singapore: A retrospective cohort study

BackgroundSocioeconomic status (SES) is likely to affect survival in breast cancer patients. Housing value is a reasonable surrogate for SES in Singapore where most residents own their own homes, which could be public (subsidised) or private housing. We evaluated effects of housing value and enhanced medical subsidies on patients’ presentation, treatment choices, compliance and survival in a setting of good access to healthcare. MethodsA retrospective analysis of breast cancer patients treated in a tertiary hospital cluster from 2000 to 2016 was performed. Individual-level Housing value Index (HI) was derived from each patient's address and then grouped into 3 tiers: HI(high)(minimal subsidy), HI(med)(medium subsidy) and HI(low)(high subsidy). Cox regression was performed to evaluate the associations between overall survival (OS) and cancer-specific survival (CSS) with HI and various factors. FindingsWe studied a multiracial cohort of 15,532 Stage 0–IV breast cancer patients. Median age was 53.7 years and median follow-up was 7.7 years. Patients with lower HI presented with more advanced disease and had lower treatment compliance. On multivariable analysis, compared to HI(high) patients, HI(med) patients had decreased OS (HR=1.14, 95% CI 1.05–1.23) and CSS (HR=1.15, 95% CI 1.03–1.27), and HI(low) patients demonstrated reduced OS (HR=1.16, 95% CI 1.01–1.33). Ten-year non-cancer mortality was higher in lower HI-strata. Enhanced medical subsidy approximately halved treatment noncompliance rates but its receipt was not an independent prognostic factor for survival. InterpretationDespite good healthcare access, lower-HI patients have poorer survival from both cancer and non-cancer causes, possibly due to delayed health-seeking and poorer treatment compliance. Enhanced subsidies may mitigate socioeconomic disadvantages. FundingNone.

Abstract 13280: Obesity is Associated With 1-year Atrial Fibrillation Recurrence After Catheter Ablation in Caucasians but Not in African Americans

Introduction: Observational studies have noted an association between body mass index (BMI) and recurrence of atrial fibrillation (AF) after catheter ablation. However, there is limited data on this association in a multi-racial cohort. We seek to describe AF recurrence after pulmonary vein isolation (PVI) of obese and non-obese patients stratified by race. Hypothesis: The association between BMI and recurrence of AF after PVI differs between Caucasians and African Americans. Methods: Caucasian and African American patients undergoing PVI at the University of Chicago from March 2016 to November 2018 were included. Patients were followed for up to 12 months. Not obese was characterized by BMI < 30kg/m 2 and obese as BMI ≥ 30kg/m 2 . Results: Among 217 consecutive patients, 69 (31.8%) were female with an average age of 64.2 years (range 24 - 89). Forty-four (20.3%) of patients were African American. There were 105 (48.4%) obese patients. No differences were observed in rates of valvular disease between non-obese and obese patients. Obesity was significant in determining time to AF recurrence after PVI (adjusted hazard ratio [aHR] 3.17, 95% CI 1.71 to 5.87, p < 0.001). When adjusted for age, gender, smoking status, hypertension, diabetes, heart failure, estimated glomerular filtration rate, and type of atrial fibrillation, Caucasians had a significant association between obesity and time to recurrence (aHR 3.34, 95% CI 1.91 to 5.85), whereas African Americans had no association between obesity and time to recurrence (aHR 0.87, 95% CI 0.31 - 2.42). This association remained when stratified by AF type. Conclusions: In this multi-racial registry of patients undergoing catheter based PVI, a BMI ≥ 30 kg/m 2 was associated with a higher likelihood of atrial fibrillation recurrence within 12 months for the Caucasian group but not amongst African Americans. These results suggest that in African Americans, obesity is less associated with recurrence of atrial fibrillation after PVI.

New onset of restless legs syndrome in pregnancy in a prospective multiracial cohort: Incidence and risk factors.

To determine whether the incidence and risk factors of restless legs syndrome (RLS) in pregnancy differ by race/ethnicity, we estimated relative risks of demographic, socioeconomic, and nutritional factors in association with risk of any incident RLS in pregnancy in a cohort of 2,704 healthy pregnant women without prior RLS. Using data from the multicenter, multiracial National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons, we examined the incidence of RLS from early pregnancy to near delivery through up to 6 assessments. Multivariable Poisson models with robust variance were applied to estimate relative risks (RRs). The cumulative incidence of RLS in pregnancy was 18.1% for all women, 20.3% for White women, 15.4% for Black women, 17.1% for Hispanic women, and 21.1% for Asian women. Among Hispanic women, older age (RR [reference ≤25 years]: 25-35 years, 1.51; 95% confidence interval [CI] 1.05-2.16; ≥35 years, 1.58; 95% CI 0.93-2.68), anemia (RR [reference no]: yes, 2.47; 95% CI 1.31-4.64), and greater total skinfolds of the subscapular and triceps sites, independent of body mass index (RR [reference quartile 1]: quartile 5, 2.54; 95% CI 1.30-4.97; p trend = 0.01) were associated with higher risk of RLS, while multiparity was associated with a lower risk (RR [reference nulliparity]: 0.69; 95% CI 0.50-0.96). In Black women, greater skinfolds and waist circumference were associated with higher risk of pregnancy RLS, although the trends were less clear. The incidence of RLS in pregnancy was high and differed by race/ethnicity, which is likely accounted for by differences in other risk factors, such as age, parity, and nutritional factors.

Clinical Features of Idiopathic Erythrocytosis in a Racially Diverse Population

Background: Idiopathic erythrocytosis (IE) is an entity characterized by a persistently elevated hemoglobin, variable erythropoietin (EPO) level, absence of janus kinase 2 (JAK2) mutations suggestive of polycythemia vera (PV) and no identifiable secondary cause. Previous studies have compared IE to PV, showing a lower incidence of venous thrombosis and leukemic transformation in IE but similar incidence of arterial events. PV is known to be associated with constitutional symptoms and splenomegaly, while hereditary erythrocytosis can be associated with recurrent headaches and fatigue. A comprehensive assessment of clinical features including symptoms in IE has not been performed. Methods: Patients signed informed consent to participate in an observational study approved by the Institutional Review Board. Enrollment criteria included: age 18 years or older; hemoglobin level greater than 16 g/dL on two occasions at least 3 months apart or greater than 15 g/dL if undergoing phlebotomy; negative testing for JAK2 mutations; and negative work up for secondary causes of erythrocytosis. Baseline assessment included history and physical exam, vital signs, pulse oximetry, and body mass index. Baseline laboratory exams included a complete blood cell count, complete metabolic panel, C-reactive protein, iron panel, ferritin, hemoglobin A1C, erythropoietin level. Abdominal ultrasound was performed to evaluate for splenomegaly. The Myeloproliferative Symptom Assessment Form (MPN-SAF) was used to assess for the presence and severity of a broad range of symptoms that may be expected to occur in patients with IE. The MPN-SAF was administered at baseline and every 6 months thereafter. Results: 35 patients had data available for analysis. Patient characteristics are shown in Table 1. The most prevalent co-morbid conditions were those known to be associated with cardiovascular disease risk and metabolic syndrome, including hepatic steatosis identified on abdominal ultrasound in 63% of patients. Three (8.6%) patients had a history of venous or arterial thrombosis. Two (5.8%) patients had a history of lymphoma (NK/T-cell and Hodgkin). Three patients (8.6%) had a first-degree relative with a myeloproliferative neoplasm (chronic myelomonocytic leukemia, essential thrombocytosis and polycythemia vera) and one patient had a son with IE and history of stroke. 16 (46%) patients were taking aspirin and 11 (31%) had undergone phlebotomy within 3 months of study enrollment. Patients reported the following symptoms on the MPN-SAF at baseline: fatigue (77%), early satiety (57%), difficulty sleeping (57%), numbness/tingling (51%), headaches (49%), concentration problems (40%), itching (40%), bone pain (37%), night sweats (37%), depression (37%), abdominal pain (37%), abdominal discomfort (37%), inactivity (37%), problems with sexual desire/function (34%), dizziness/lightheadedness (31%), cough (26%), fever (17%), and unintentional weight loss (17%). Fatigue carried the highest average symptom intensity (3.77, SD 3.17). Discussion: In this study, we describe the clinical features associated with IE in a multiracial cohort. Patients with IE are frequently symptomatic and have a high incidence of hepatic steatosis by ultrasound. Disclosures No relevant conflicts of interest to declare.

Oncological safety and postoperative complications in oncoplastic breast surgery among Asian women: A single institutional review.

Oncoplastic breast surgery (OBS) improves margin clearance and produces good esthetic outcome in breast cancer treatment. This study evaluates the complications and outcome of OBS in a multiracial patient cohort. Data of 421 patients between 2011 and 2018 were analyzed. The majority were Malays (41.8%), followed by Chinese (39.7%) and Indians (16.8%). Low local complications were noted, with no significant differences in disease-free survival (P=.927) and overall survival (P=.719) between low and high OBS levels. Shared decision-making in offering OBS for Asian women has potential to become a practical option in breast cancer treatment.

Adipokines in early and mid-pregnancy and subsequent risk of gestational diabetes: a longitudinal study in a multiracial cohort

IntroductionSeveral adipokines are implicated in the pathophysiology of gestational diabetes mellitus (GDM), however, longitudinal data in early pregnancy on many adipokines are lacking. We prospectively investigated the association of a...

Relationship Between Dietary Magnesium Intake and Incident Heart Failure Among Older Women: The WHI.

BackgroundWomen represent a large proportion of the growing heart failure (HF) epidemic, yet data are lacking regarding optimal dietary and lifestyle prevention strategies for them. Specifically, the association between magnesium intake and HF in a multiracial cohort of women is uncertain.Methods and ResultsWe included 97 725 postmenopausal women from the WHI (Women's Health Initiative) observational studies and placebo arms of the hormone trial. Magnesium intake was measured at baseline by a 122‐item validated food‐frequency questionnaire and stratified into quartiles based on diet only, total intake (diet with supplements), and residual intake (calibration by total energy). Incident hospitalized HF (2153 events, median follow‐up 8.1 years) was adjudicated by medical record abstraction. In Cox proportional hazards models, we evaluated the association between magnesium intake and HF adjusting for potential confounders. Analyses were repeated on a subcohort (n=18 745; median‐follow‐up, 13.2 years) for whom HF cases were subclassified into preserved ejection fraction (526 events), reduced ejection fraction (291 events) or unknown (168 events). Most women were white (85%) with a mean age of 63. Compared with the highest quartile of magnesium intake, women in the lowest quartile had an increased risk of incident HF, with adjusted hazard ratios of 1.32 (95% CI, 1.02–1.71) for diet only (P trend=0.03), 1.26 (95% CI, 1.03–1.56) for total intake, and 1.31 (95% CI, 1.02–1.67) for residual intake. Results did not significantly vary by race. Subcohort analyses showed low residual magnesium intake was associated with HF with reduced ejection fraction (hazard ratio, 1.81, lowest versus highest quartile; 95% CI, 1.08–3.05) but not HF with preserved ejection fraction.ConclusionsLow magnesium intake in a multiracial cohort of postmenopausal women was associated with a higher risk of incident HF, especially HF with reduced ejection fraction.

Abstract MP74: Association of Albuminuria With Incident Atrial Fibrillation: The Multi-ethnic Study of Atherosclerosis (MESA)

Background: Atrial fibrillation (AF) shares risk factors with atherosclerotic cardiovascular disease (CVD). Albuminuria (AU) is an established risk factor for renal failure and CVD. Endothelial dysfunction, inflammation and hemostasis underlie the pathogenesis of AU. However, the association of AU with incident AF and its effect modifiers are not fully understood. Purpose: To assess the association of AU with incident AF and to identify its effect modifiers. Methods: We studied MESA participants, free of clinical CVD and AF at baseline, with urine samples at exam 1. Participants were followed for incident AF ascertained by follow up visit ECGs, hospital discharge diagnoses or Medicare claims data. Participants were compared by the presence or absence of AU (albumin-creatine ratio of ≥30). Kaplan-Meier curves were used to estimate the cumulative rate of incident AF and log-rank test to evaluate statistical significance. Hazard ratio (HR) and 95% confidence interval (CI) were computed by Cox proportional hazard models. Final adjusted model included CHARGE-AF risk score covariates with socioeconomic variables, current alcohol use, renal function, and lipid lowering medication use. Results: A total of 6376 participants were analyzed (median age 62 years, male 47.4%, White race 38.8%, mean BMI 28.3 ± 5.5). During median follow-up of 13.9 years, there were a total of 924 AF events. Participants with AU had a higher incidence of AF than those without AU at 10 years (23.9% vs 10.4%, p < 0.05, Figure 1A ). In fully adjusted model, AU was significantly associated with incident AF [HR 1.53 (95% CI 1.27 - 1.85, p < 0.01). Low high-density lipoprotein cholesterol (< 40 mg/dL) and high triglyceride (≥ 150 mg/dL) augmented the association between AU and incident AF (p-interaction < 0.05 for all, Figure 1B ). Conclusion: AU was significantly associated with incident AF after adjusting for conventional risk factors in a multi-racial prospective cohort. Lipid markers were identified as effect modifiers in the association of AU with AF.

Dual Induction Therapy after Pediatric Kidney Transplantation in a Multiracial Cohort: A Single Center Experience

Dual Induction Therapy after Pediatric Kidney Transplantation in a Multiracial Cohort: A Single Center Experience

935: Racial/ethnic disparities in glycemic control among women with gestational diabetes: A multiracial pregnancy cohort study

935: Racial/ethnic disparities in glycemic control among women with gestational diabetes: A multiracial pregnancy cohort study

PTRF independently predicts progression and survival in multiracial upper tract urothelial carcinoma following radical nephroureterectomy

ObjectivesPolymerase I and transcript release factor (PTRF) has been implicated in cancer biology but its role in upper tract urothelial carcinoma (UTUC) is unknown. From a pilot transcriptome, we identified PTRF was significantly upregulated in high stage UTUC. Bladder cancer transcriptome from The Cancer Genome Atlas (TCGA) supported our finding and high PTRF level also predicted poor survival. We, therefore, investigated the correlation of PTRF with patients’ clinicopathologic characteristics and outcomes in a multiracial UTUC cohort. Materials and methodsBy immunohistochemical staining, PTRF expression was determined using H-score. PTRF expression of 575 UTUCs from 8 institutions, including 118 Asians and 457 Caucasians, was compared with various clinicopathologic parameters. Human urothelial cancer cell lines were used to evaluate the level of PTRF protein and mRNA expression, and PTRF transcript level was assessed in fresh samples from 12 cases of the cohort. The impact of PTRF expression on disease progression, cancer-specific death and overall mortality was also examined. ResultsHigh PTRF expression was significantly associated with multifocality (P = 0.023), high pathologic tumor stage (P < 0.00001), nonurothelial differentiation (P = 0.035), lymphovascular invasion (P = 0.003) and lymph node metastasis (P = 0.031). PTRF mRNA expression was also markedly increased in advanced stage UTUC (P = 0.0003). High PTRF expressing patients had consistently worse outcomes than patients with low PTRF expression regardless of demographic variation (all P < 0.005). In multivariate analysis, high PTRF expression was an independent predictor for progression-free survival (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.07–2.69, P = 0.025), cancer-specific survival (HR 2.09, 95% CI 1.28–3.42, P = 0.003), and overall survival (HR 2.04, 95% CI 1.33–3.14, P = 0.001). ConclusionsResults indicate that PTRF is a predictive biomarker for progression and survival and an independent prognosticator of UTUC. Elevated PTRF could probably propel clinically aggressive disease and serve as a potential therapeutic target for UTUC.

The utility of voriconazole therapeutic drug monitoring in a multi-racial cohort in Southeast Asia

ObjectivesVoriconazole serum concentration, which is affected by several factors, is associated with treatment response and toxicity. There is paucity of data on voriconazole therapeutic drug monitoring (TDM) among Southeast Asians, who exhibit a higher prevalence of CYP2C19-poor metabolisers compared with Caucasians and East Asians. Hence, there are concerns for higher risk of voriconazole accumulation and toxicity.We aim to determine the utility of voriconazole TDM through establishing: (1) proportion of patients achieving therapeutic troughs without dose adjustments; (2) characterisation of patients with sub-therapeutic, therapeutic and supra-therapeutic levels; (3) appropriate dose titrations/dose required for therapeutic troughs; (4) correlation between troughs and adverse events, treatment response/fungal breakthrough. Patients and methodsA single-centre retrospective analysis of data from adults (≥21 years old) with ≥1 voriconazole trough measured at Singapore General Hospital from 2015 to 2017 was performed. ResultsThirty-two patients (45.7%) among 70 patients achieved therapeutic troughs (defined as 2.0–5.5 mg/L) without dose adjustments. Eleven patients (15.7%) experienced hepatotoxicity (troughs 0.5 to >7.5 mg/L). Neurotoxicity occurred in three patients (4.3%) (troughs ≥6.7 mg/L) and all patients had symptom resolution upon dose reduction. Treatment failure of invasive fungal infection appeared less in patients with therapeutic troughs compared with sub-therapeutic troughs (11.4% vs. 14.2%). Two patients experienced treatment failure despite supra-therapeutic voriconazole troughs. ConclusionsTDM should be implemented due to significant unpredictability in dose exposure. TDM can reduce unnecessary switches to alternatives due to intolerability and rule in the possibility of resistant organisms in the event of treatment failure despite therapeutic troughs, alerting clinicians to switch to alternatives promptly.

Effects of hydrochlorothiazide on drainage volume and seroma formation in deep inferior epigastric perforator flap breast reconstruction: Randomized controlled trial

Seroma is a recognized complication encountered at the reconstructed breast and donor site after abdominal-based breast reconstruction. Seroma is caused by lymphatic channel disruption and the formation of a large space between the deep fascia during flap elevation. Surgical techniques to preserve the lymphatics and secure the closure of the donor site can reduce seroma formation. This study investigated the safety and effectiveness of the diuretic hydrochlorothiazide at reducing interstitial fluid accumulation and seroma formation during deep inferior epigastric perforator (DIEP) flap breast reconstruction. Sixty patients with breast cancer who underwent skin- or nipple-sparing mastectomy and DIEP flap reconstruction were enrolled between August 2016 and June 2017. The patients were randomly assigned to receive either 25mg per day of hydrochlorothiazide from the second to the twentieth day after surgery (treatment) or no diuretic (control). The clinicopathological characteristics, drainage time, and drainage volume were statistically compared between the two groups. The average total drainage volume at the donor site was 291mL in the treatment group and 434mL in the control group (p = 0.003). The differences in body mass index and flap weight between the two groups were not statistically significant (p = 0.879 and p = 0.963, respectively). No hypotension or electrolyte imbalance was noted during the follow-up. Intake of 25mg per day of hydrochlorothiazide tablets effectively reduced the total abdominal drainage volume and removal time of indwelling drains. However, the adverse effects should be further investigated in a large population and multiracial cohort before using hydrochlorothiazide for seroma prevention.

Examining the validity of a predictive model for vaginal birth after cesarean.

Background The Maternal-Fetal Medicine Units (MFMU) vaginal birth after cesarean (VBAC) calculator, while accurate for candidates with high predicted success rates, is not as accurate for poor candidates. This study examines the calculator's validity in an understudied multiracial cohort with a high proportion of poor candidates. Methods This retrospective study examined women with one or two prior cesarean deliveries who attempted VBAC at a single institution. Subjects were placed into quartiles based on MFMU-predicted success rates. For each quartile, actual and predicted success rates were compared. The calculated area under the receiver operating characteristic curve (AUC) was compared to the original AUC. Results The study included 1604 women. Actual and predicted VBAC rates were similar in the lowest and highest quartile groups, 18.2% vs. 21.2% (n = 11, P > 0.99) and 87.1% vs. 88.5% (n = 1090, P = 0.14), respectively. In the 51-75% predicted success rate group, the actual VBAC rate was higher than the predicted rate, 69.9% vs. 65.5% (n = 394) but not statistically significant (P = 0.07). In the 25-50% predicted success rate group, the actual VBAC rate was significantly higher than the predicted rate 55.1% vs. 39.6% (n = 109, P = 0.002). The actual AUC was lower than the MFMU model, 0.72 [95% confidence interval (CI) 0.69-0.75] vs. 0.77 (95% CI 0.76-0.78) (P < 0.001). Conclusion The MFMU VBAC calculator's predicted success rates were comparable to actual success rates for candidates with predicted success rates >75%. As predicted success rates declined, the calculator was increasingly inaccurate and underestimated the success rate. Caution should be taken when using the MFMU VBAC calculator for poor candidates.

To ‘Look Smart’ and Run Fast: Jamaican Track Athletes and the Advertisement of Creole Nationalism at the 1948 Olympic Games

At the 1948 London Olympic Games, the colony of Jamaica made its Olympic debut. In a postwar moment that presaged the possibility of greater self-governance for colonized places, participation in the foremost international athletic festival provided an opportunity for the island to promote and perform a national identity. On and off the track, Jamaica’s track stars communicated creole nationalism, the island’s nationalist ideology that balanced Jamaican pride with British propriety. The multiracial and mixed-gender cohort of track athletes was understood as safely and successfully symbolizing the island’s nationalist aspirations because they adhered to colonially-imposed hierarchies of race, color, class, and gender. Their careful presentation demonstrated Jamaican character and capacity, while also reinforcing a commitment to the cultural values of Britain. The praise for Jamaica’s Olympians in the Jamaican, British, and American presses indicates their effectiveness. However, because Jamaica’s athletes expertly abided by traditional racial, color, class, and gender arrangements, they reinforced the relevance of these distinctions, inscribing them into the island’s nationalist project. Jamaica’s inaugural Olympic experience thus illuminates how the politics of identity structured the possibilities and limitations of the eventual Jamaican nation.

A Prospective Study of Leukocyte Telomere Length and Risk of Gestational Diabetes in a Multiracial Cohort.

Short telomere length (TL), an indicator of cellular aging and oxidative stress, has been implicated in glucose homeostasis. Additionally, studies have illustrated that the association of TL with health outcomes may vary by age. Yet, data on the association between TL and gestational diabetes mellitus (GDM) are sparse and the potential effect modification by age remains unknown. We prospectively investigated TL in early pregnancy in relation to the subsequent GDM risk in a case-control study of 93 women with GDM and 186 randomly selected controls matched on age, race/ethnicity, and gestational weeks at blood collection. TL was measured using blood samples collected at 10-14 gestational weeks and reported as the T/S ratio, a ratio of telomere repeat length T to copy number of a single copy gene S. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression adjusted for major risk factors. Overall, TL was not significantly associated with GDM risk. The TL-GDM association was significantly modified by age (Pinteraction = 0.02). Shorter TL in early pregnancy was associated with an increased GDM risk among women <30 years old (adjusted OR comparing the shortest vs. longest tertile: 3.1, 95% CI = 1.2, 8.1), but not associated with GDM risk among women ≥30 years. Our findings suggest that TL in early pregnancy may be implicated in GDM development, particularly among younger women.

2107. Azole Therapeutic Drug Monitoring (TDM) in a Multiracial Cohort with Varied Pharmacogenetics

BackgroundVoriconazole (VOR) and posaconazole (POS) exhibit wide pharmacokinetic variability. Various factors including race and genetic polymorphisms are at play and this may affect treatment response. We aim to evaluate the utility of VOR/POS TDM among Southeast Asians that are predominantly intermediate/poor VOR metabolizers.MethodsAll adults with VOR/POS TDM performed at our institution from 2015 to 2018 were included. We determined proportion of patients and doses required to achieve TDM targets [(2 – 5.5 mg/L (VOR) or ≥ 0.7 and ≥ 1.0 mg/L (POS prophylaxis and treatment respectively)], and correlate levels with treatment efficacy and safety.ResultsVOR/POS TDM was performed mostly among patients with hematological malignancy or solid-organ transplant (146/174, 83.9%). Less than half (32/70, 45.7%) of patients on VOR achieved target—18 (25.7%) were < 2 mg/L while 20 (28.5%) had levels > 5.5 mg/L. Doses required to achieve TDM target ranged from 1.9–11.4 mg/kg/day. Drug interactions, critically ill state and change in drug formulation were major causes of intra-patient variability. One-fifth (n = 14) experienced transaminitis; corresponding VOR trough levels were 0.5–> 7.5 mg/L. Neurotoxicity was also seen in 3 (4.3%) patients—all 3 had VOR trough ≥ 6.7 mg/L and saw symptom resolution upon dose reduction. There appears to be no association between the achievement of TDM targets and response rates. Majority (81/104, 77.9%) of patients on POS achieved TDM targets. Patients prescribed POS tablet were significantly more likely to attain targets compared with suspension 600 mg/day [19/26 (73.0%) vs. 27/62 (43.5%), P < 0.05] and 800 mg/day [17/26 (65.3%) vs. 4/16 (25.0%), P < 0.05)]. Of 23 with sub-therapeutic levels, 19 (82.6%) responded to dose increase and/or change in acid-reducing agents. Breakthrough infection occurred despite troughs ≥ 0.7 mg/L [5/42 (11.9%) vs. 2/40 (5.0%) when < 0.7 mg/L (P = 0.3)]. Treatment failure was observed in 2 patients (troughs > 1.0 mg/L).ConclusionVOR/POS TDM should be implemented in Southeast Asians due to significant unpredictability in dose exposure and potential to avoid need for switch to alternative anti-fungals due to intolerability. Higher POS trough cutoff may be required for effective anti-fungal prophylaxis.Disclosures All authors: No reported disclosures.

1080 Bilirubin and QT Interval Prolongation (From the Third National Health and Nutrition Examination Survey)

INTRODUCTION: The association of bilirubin with cardiovascular disease (CVD) is controversial. We sought to explore the association of total bilirubin levels with QT interval in a multiracial cohort. METHODS: A total of 6,627 participants (59.0 ± 13.3 years; 52.6%% women, 49.7% Non-Hispanic Whites) without cardiovascular disease (CVD) from the Third National Health and Nutrition Examination Survey (NHANES-III) were included in this analysis. QT was automatically measured from digital 12-lead electrocardiogram in a central reading center. A multivariable logistic regression model was used to examine cross-sectional association between tertiles of total bilirubin and prolonged QT interval (≥450 ms in men, ≥460 ms in women). RESULTS: The prevalence of prolonged QT was higher among those with higher levels of total bilirubin (prolonged QT prevalence was 4.7%, 6.8%, and 7.0% across total bilirubin lower (0-0.4 mg/dl), middle (0.5-1.6 mg/dl) and higher (0.70-4.30 mg/dl) tertiles respectively). In a model adjusted for potential confounders, participants within the highest total bilirubin tertile had significantly greater odds of prolonged QT interval (OR (95% CI): 1.53 (1.16-2.02) compared to those with bilirubin levels in the first tertile. Each 0.29 mg/dl increase in total bilirubin levels was associated with a 12% (P-value &lt; .0001) increase in the prevalence of prolonged QT interval (Table 1). This association was stronger in men than women (interaction P-value = 0.04). CONCLUSION:: Recent evidence suggests worse cardiovascular (CV) outcomes with high levels of bilirubin but the mechanism behind worse CV events remains to be elucidated. Our study showed that elevated bilirubin levels are associated with prolonged QT interval. QT interval has been consistently associated with increased risk of all-cause and CV death. Thus, finding an association between total bilirubin levels and prolonged QT interval in our study extends our current knowledge on the relationship between serum bilirubin and CVD by demonstrating a link between higher total bilirubin and abnormal cardiac repolarization. To the best of our knowledge, this is the first study to demonstrate the association between bilirubin and prolonged QT. This association was stronger in men than women. Future studies are needed to establish the causal relationship between bilirubin and QT prolongation and how this association between bilirubin and QT interval could be harnessed to improve CVD risk estimation.