Multiethnic Cohort Of Patients Research Articles

Survival analysis of mortality and development of lupus nephritis in patients with systemic lupus erythematosus up to 40 years of follow-up.

Patients with SLE have increased mortality compared with age- and sex-matched controls. LN is a severe manifestation of SLE and an important cause of death. We carried out a retrospective survival analysis to investigate factors that could influence the risk of mortality and LN in a large multi-ethnic cohort of patients with SLE. By careful review of medical records, we identified 496 patients with SLE for whom we had complete information regarding the period of observation and occurrence of death and nephritis. Patients were stratified into groups according to sex, ethnicity, age at start of follow-up and time period of diagnosis. Kaplan-Meier analysis was used to investigate differences between the groups. Of the 496 patients in the study, 91 (18.3%) died, 165 (33.3%) developed LN and 33 (6.7%) developed end-stage renal failure. There was no difference between men and women in either mortality or development of LN. Caucasian patients were significantly less likely to develop LN than other ethnic groups (P < 0.0001) but not less likely to die. Patients diagnosed before the median age of 28 years were significantly more likely to develop LN (P < 0.0001) but significantly less likely to die (P = 0.0039) during the period of observation. There has been a significant improvement in survival in patients diagnosed between 1978 and 1989 and those diagnosed between 2006 and 2011 (P = 0.019). In our cohort, non-Caucasian ethnicity and younger age at diagnosis are associated with the risk of developing LN. There is evidence of improvement in survival of patients with SLE over time.

Hungry bone syndrome following parathyroidectomy for primary hyperparathyroidism in a developed country in the Asia Pacific. A cohort study

ObjectivesWe sought to assess the incidence of hungry bone syndrome (HBS) following parathyroidectomy (PTX) for primary hyperparathyroidism (PHPT) in a cohort of multi-ethnic patients from a developed country in the Asia Pacific. MethodsOne hundred and sixty-four patients who underwent PTX for PHPT between 2012 and 2019 at the 2 largest public hospitals in Singapore were identified. HBS was defined as serum albumin-adjusted calcium ≤ 2.1 mmol/L with normal or raised serum intact parathyroid hormone (iPTH) levels, manifesting on or after the 3rd day, or persisting for more than 3 days post-operatively. ResultsChinese constituted 73.8%, Malays 12.2%, Indians 9.8%, and other races 4.3%. HBS developed in 4 patients (2.4%) (95% CI, 0.8%–6.5%). HBS patients had significantly longer in-hospital stays; 20 days [IQR:15–22] vs 2 days [IQR:1–3]; P < 0.001in those who did not develop HBS. There was no difference in the incidence of HBS stratifying for age, sex, vitamin D status, or use of preoperative anti-resorptive medication use. For every 10 unit increase in iPTH and alkaline phosphatase (ALP) levels, the risk of HBS increased by 14% and 11%; RR (95% CI), 1.14 (1.05–1.21) and 1.11 (1.03–1.18), respectively. ConclusionsThe low incidence of HBS in multi-ethnic patients undergoing PTX by multiple surgeons for PHPT at the 2 largest public hospitals that see the most such patients in Singapore, a developed country, is consistent with the asymptomatic/milder form of presentation of PHPT in the developed world.

The Birmingham and Black Country cohort of Venous Thromboembolism (BBC-VTE) registry: Rationale, design and preliminary results

The Birmingham Black Country Venous Thromboembolism registry (BBC-VTE) is a multi-ethnic cohort of patients who suffered a first episode of venous thromboembolism (VTE) and were admitted to various hospital sites across the West Midlands and Black Country regions in the United Kingdom. The BBC-VTE registry is a retrospective, observational cohort study which aims to collect data on outcomes including mortality, bleeding and VTE recurrence in this patient cohort. In addition, the comprehensive, structured data collected will allow us to conduct machine learning analyses for risk prediction in such patients and also to compare to previously derived mortality scores such as the PESI and the simplified PESI (sPESI).Our registry included 2183 patients admitted to hospital between the years 2012–14 and 2016–18 with a first episode of VTE and the mean follow up was 36 months. The cohort was ethnically diverse with 72.5% white Caucasian, 8.2% Asian (including South Asian), 6.7% black, and 11.7% of unknown/other ethnicity. Of those admitted during the collection period 56% had PE, 40% had DVT, with the rest presenting with both PE and DVT. Around 7% of patients went on to develop a bleeding episode and 36% died (all-cause mortality). Of the deaths, 10% of patients died within 30-days of admission (30-day mortality), with 16% dying within 90 days. In summary, this study investigates real-world outcomes of patients after the first index VTE event and attempts to bridge the gap in evidence for contemporary data in this population which will allow to construct more accurate risk prediction tools and management decisions.

Response to Vaccination Against SARS-CoV-2 in Patients With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Renal Involvement.

BackgroundPatients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) present with multisystem disease including renal impairment. The treatment for AAV involves a high burden of immunosuppression. Patients with renal involvement are treated especially intensively. As a result, we identified these patients as being potentially at high risk of failure to seroconvert to COVID-19 vaccination.MethodsWe collected data on seroconversion response rates to COVID-19 vaccination in a multi-ethnic cohort of patients with AAV and renal involvement treated at a busy tertiary nephrology centre as part of a retrospective review of patient notes. Blood samples were taken following vaccination with either Pfizer or Astra-Zeneca COVID-19 vaccines and median fluorescence intensity was measured using the validated MULTICOV-Ab Magnetic LuminexⓇ Assay. We also evaluated whether seroconversion was affected by immunosuppression regimen.Results81 patients were included. The mean age was 62, and there were 49 (60%) females. 55 patients had a blood test after the first dose; 46 after the second dose. Patients were in remission with a median BVAS of 0 (IQR 2). Seroconversion after the first dose with either vaccine was 35/55 (63.6%). After the second it was 38/46 (82.6%). Subgroup analyses revealed a trend to impaired seroconversion in non-white versus white patients (77.8 vs. 81.7% (p = 0.69) after the first dose of vaccine and in those treated with Rituximab in the last 12 months (73.3 vs. 87.1%, p = 0.41).ConclusionsThese data offer real-world evidence of lower seroconversion in response to vaccination with one dose in patients with AAV and renal involvement than the general UK population. After two doses, seroconversion is in line with national data. These data provide a rationale for hospital-led identification of patients most at risk of COVID-19 and underscore the importance of local connexions between hospitals and their communities. These data provide further support for targeting booster vaccination programmes to vulnerable patient cohorts. They add to the growing evidence of reduced seroconversion in response to vaccination in patients with renal disease of any cause.

Off-Therapy Response After Nucleos(t)ide Analogue Withdrawal in Patients With Chronic Hepatitis B: An International, Multicenter, Multiethnic Cohort (RETRACT-B Study)

Functional cure, defined based on hepatitis B surface antigen (HBsAg) loss, is rare during nucleos(t)ide analogue (NA) therapy and guidelines on finite NA therapy have not been well established. We aim to analyze off-therapy outcomes after NA cessation in a large, international, multicenter, multiethnic cohort of patients with chronic hepatitis B (CHB). This cohort study included patients with virally suppressed CHB who were hepatitis B e antigen (HBeAg)-negative and stopped NA therapy. Primary outcome was HBsAg loss after NA cessation, and secondary outcomes included virologic, biochemical, and clinical relapse, alanine aminotransferase flare, retreatment, and liver-related events after NA cessation. Among 1552 patients with CHB, cumulative probability of HBsAg loss was 3.2% at 12 months and 13.0% at 48 months of follow-up. HBsAg loss was higher among Whites (vs Asians: subdistribution hazard ratio, 6.8; 95% confidence interval, 2.7-16.8; P < .001) and among patients with HBsAg levels <100 IU/mL at end of therapy (vs ≥100 IU/mL: subdistribution hazard ratio, 22.5; 95% confidence interval, 13.1-38.7; P < .001). At 48 months of follow-up, Whites with HBsAg levels <1000 IU/mL and Asians with HBsAg levels <100 IU/mL at end of therapy had a high predicted probability of HBsAg loss (>30%). Incidence rate ofhepatic decompensation and hepatocellular carcinoma was0.48 per 1000 person-years and 0.29 per 1000 person-years, respectively. Death occurred in 7/19 decompensated patients and 2/14 patients with hepatocellular carcinoma. The best candidates for NA withdrawal are virally suppressed, HBeAg- negative, noncirrhotic patients with CHB with low HBsAg levels, particularly Whiteswith <1000 IU/mL and Asians with <100 IU/mL. However, strict surveillance is recommended to prevent deterioration.

Accuracy of a Deep Learning System for Classification of Papilledema Severity on Ocular Fundus Photographs.

To evaluate the performance of a deep learning system (DLS) in classifying the severity of papilledema associated with increased intracranial pressure on standard retinal fundus photographs. A DLS was trained to automatically classify papilledema severity in 965 patients (2,103 mydriatic fundus photographs), representing a multiethnic cohort of patients with confirmed elevated intracranial pressure. Training was performed on 1,052 photographs with mild/moderate papilledema (MP) and 1,051 photographs with severe papilledema (SP) classified by a panel of experts. The performance of the DLS and that of 3 independent neuro-ophthalmologists were tested in 111 patients (214 photographs, 92 with MP and 122 with SP) by calculating the area under the receiver operating characteristics curve (AUC), accuracy, sensitivity, and specificity. Kappa agreement scores between the DLS and each of the 3 graders and among the 3 graders were calculated. The DLS successfully discriminated between photographs of MP and SP, with an AUC of 0.93 (95% confidence interval [CI] 0.89-0.96) and an accuracy, sensitivity, and specificity of 87.9%, 91.8%, and 86.2%, respectively. This performance was comparable with that of the 3 neuro-ophthalmologists (84.1%, 91.8%, and 73.9%, p = 0.19, p = 1, p = 0.09, respectively). Misclassification by the DLS was mainly observed for moderate papilledema (Frisén grade 3). Agreement scores between the DLS and the neuro-ophthalmologists' evaluation was 0.62 (95% CI 0.57-0.68), whereas the intergrader agreement among the 3 neuro-ophthalmologists was 0.54 (95% CI 0.47-0.62). Our DLS accurately classified the severity of papilledema on an independent set of mydriatic fundus photographs, achieving a comparable performance with that of independent neuro-ophthalmologists. This study provides Class II evidence that a DLS using mydriatic retinal fundus photographs accurately classified the severity of papilledema associated in patients with a diagnosis of increased intracranial pressure.

Recurrent pterygium in Bintulu, Sarawak (Malaysian Borneo): determining its risk factors

Introduction: Pterygium may give rise to astigmatism in addition to causing blindness in advanced stages, reflecting the importance of timely surgical intervention. Despite various operative approaches, the recurrence rate continues to range from 2% to 89%. Therefore, it is essential to investigate the risk factors influencing recurrence to improve therapeutic strategies.&#x0D; Purpose: To determine the risk factors of pterygium recurrence among the multiethnic cohort of patients in Bintulu, Sarawak (Malaysian Borneo).&#x0D; Study design: Retrospective cohort.&#x0D; Materials and methods: This study was conducted in Bintulu Hospital, Sarawak and involved patients who underwent pterygium excision with conjunctival autografting between April 1, 2016 and May 31, 2019. Patients completed at least a year of follow-up for recurrence detection. Collected data included presence of recurrence, sociodemographics, outdoor activities, habits, first-degree family history, pterygium type and location, as well as laterality. Chi-squared test, Fisher’s exact test, and logistic regression analysis were used.&#x0D; Results: A total of 161 eyes that underwent pterygium excision in 137 patients were identified. Percentage of recurrence was 42%. Mean age during excision was 59.3 ± 11.5 years; age group showed no significance in pterygium recurrence (p = 0.447). Male gender showed statistical significance (p = 0.045, OR 1.90, CI 1.01, 3.58) in chi-squared test but not in logistic regression. Ethnicity, marital status, income, and education level showed no association with recurrence (p &gt; 0.05). Anatomic factors like location (p = 0.353) and laterality (p = 0.955) also showed no association. Smoking (p = 0.867) and alcohol intake (p = 0.397) were insignificant, similar to first-degree family history (p = 0.137). Activities involving sun exposure (p &lt; 0.001, OR 18.34, 95% CI 5.59, 60.17) and recurrent pterygium type (p = 0.001, OR 7.40, 95% CI 1.81, 30.21) supported a positive association with recurrence. Medication adherence (p &lt; 0.001, OR 3.61, 95% CI 1.07, 12.21) and the use of sun protection (p &lt; 0.001, OR 7.90, 95% CI 3.25, 19.19) showed a statistically significant decrease in recurrence.&#x0D; Conclusion: Activities involving sun exposure, use of sun protection, medication adherence, and recurrent pterygium type have shown to be statistically significant in influencing pterygium recurrence.

The utility of ALS staging systems in a multi-ethnic patient cohort

Objective: To compare two ALS staging systems, King’s clinical staging and Milano-Torino (MiToS) functional staging, using prospective data from a multi-ethnic cohort of ALS patients. Methods: The stages of disease were determined prospectively based on existing definitions. The two systems were compared for timing of stages using box plots, correspondence using chi-square tests and association using Spearman’s rank correlation. Results: The distribution of stages differed between the two systems. The proportions of disease stages of the King’s staging system were more evenly distributed whereas in MiToS, there was greater weight seen at the later stages of disease. At the early stages, patients moved consecutively in the MiToS staging system but not in the King’s staging system where patients tended to skip stages to reach later stages. Both systems had good correlation (Spearman’s rho = 0.869) and the King’s stage 4 most frequently corresponded to MiToS stage 2. Conclusion: We found the King’s staging was helpful in determining the stages of disease burden, whereas both were helpful in determining the time to functional dependence with MiToS further refining the levels of dependence.

Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy.

Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m2, P<0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P=0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P<0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P=0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P<0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P=0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7, whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P<0.0001). There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine-based care of individuals with hypertrophic cardiomyopathy.

Using Ultrasound and Inflammation to Improve Prediction of Ischemic Stroke: A Secondary Analysis of the Multi-Ethnic Study of Atherosclerosis

Introduction: Current ischemic stroke risk prediction is primarily based on clinical factors, rather than imaging or laboratory markers. We examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary ischemic stroke risk. Methods: In this secondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), the primary outcome is the incident ischemic stroke during follow-up. The predictor variables are 9 carotid ultrasound-derived measurements and 6 serum inflammation measurements from the baseline study visit. We fit Cox regression models to the outcome of ischemic stroke. The baseline model included patient age, hypertension, diabetes, total cholesterol, smoking, and systolic blood pressure. Goodness-of-fit statistics were assessed to compare the baseline model to a model with ultrasound and inflammation predictor variables that remained significant when added to the baseline model. Results: We included 5,918 participants. The primary outcome of ischemic stroke was seen in 105 patients with a mean follow-up time of 7.7 years. In the Cox models, we found that carotid distensibility (CD), carotid stenosis (CS), and serum interleukin-6 (IL-6) were associated with incident stroke. Adding tertiles of CD, IL-6, and categories of CS to a baseline model that included traditional clinical vascular risk factors resulted in a better model fit than traditional risk factors alone as indicated by goodness-of-fit statistics. Conclusions: In a multiethnic cohort of patients without cerebrovascular disease at baseline, we found that CD, CS, and IL-6 helped predict the occurrence of primary ischemic stroke. Future research could evaluate if these basic ultrasound and serum measurements have implications for primary prevention efforts or clinical trial inclusion criteria.

Clinical and economic burden of diabetic foot ulcers: A 5-year longitudinal multi-ethnic cohort study from the tropics.

Diabetic foot ulcers (DFUs) present a substantial clinical and economic burden to healthcare systems around the world, with significant reductions in quality of life for those affected. We aimed to analyse the clinical and economic burden of DFU via a 5‐year longitudinal multi‐ethnic cohort study. A longitudinal analysis of inpatient and outpatient DFUs data over 5 years from a university tertiary hospital in Singapore was performed. Data included baseline characteristics, clinical outcomes, hospitalisation, and outpatient details. Descriptive statistics, Kaplan–Meier survival analyses, and Cox proportional hazard models were performed. Patients treated for DFUs (n = 1729, mean patient age of 63·4 years) were assessed. The cohort consists of Chinese (61.4%), Malay (13.5%), and Indian (18.4%) patients. Common comorbidities included peripheral arterial disease (74.8%), peripheral neuropathy (14.5%), and a median haemoglobin A1c of 9.9%. Patients underwent toe(s) amputation (36.4%), transmetatarsal amputations (16.9%), or major amputations (6·5%). The mean length of inpatient stay for ulcer‐only, minor amputation, and major amputation was 13.3, 20.5, and 59.6 days, respectively. Mean cost per patient‐year was US $3368 (ulcer‐only), US $10468 (minor amputation), and US $30131 (major amputation). Minor amputation‐free survival was 80.9% at 1 year and 56.9% at 5 years, while major amputation‐free survival was 97.4% at 1 year and 91.0% at 5 years. In conclusion, within our multi‐ethnic cohort of patients from the tropics, there was significant clinical and economic burden of DFUs, with a high wound per patient ratio and escalating healthcare costs corresponding to more proximal amputation levels.

Long-term Efficacy of Mitomycin C Augmented Trabeculectomy in a Mixed Pediatric Glaucoma Cohort.

This paper reports a retrospective consecutive case series investigating the efficacy of Mitomycin C-augmented trabeculectomy in the treatment of primary and secondary pediatric glaucoma in a mixed etiology, multiethnic cohort of patients. To evaluate the long-term efficacy and safety of Mitomycin C-augmented trabeculectomy in a mixed, tertiary-referral, pediatric glaucoma cohort. Retrospective consecutive review of all children (37 eyes) undergoing Mitomycin C-augmented trabeculectomy by a single surgeon between 2008 and 2016. Seventeen eyes (45.9%) had primary congenital glaucoma, and 20 eyes (54.1%) had secondary glaucoma. The median age at surgery was 11 months (range, 2 to 146). The mean follow-up was 69.2±4.7 months (range, 3.5 to 107.9). Overall, trabeculectomy was successful in 80.6% of eyes at 12 months, 60.5% at 3 years, and 57.5% at 5 years. 45.9% cases (17 eyes) required further laser or surgery for uncontrolled intraocular pressure (IOP) and were therefore deemed as failures. The time to failure ranged from 0.4 to 65.1 months (mean, 22.2±5.1 mo). The proportion of children achieving visual acuity of 1.0 LogMAR equivalent or better increased from 43.2% preoperatively to 63.6% at 1 year and 68% at 5 years. The mean IOP reduced from 24.85±0.88 mm Hg preoperatively to 15.14±0.94 mm Hg at 3 months (39% reduction) and 17.42±1.08 mm Hg at 5 years (30% reduction). IOP-lowering medication requirement reduced from 4.14±0.20 agents preoperatively to 0.84±0.22 at 3 months (80% reduction) and 1.78±0.36 at 5 years (57% reduction). There were no sight-threatening complications such as hyphaema, bleb leak, chronic hypotony, endophthalmitis, retinal detachment, or loss of light perception. This study provides valuable evidence that Mitomycin C-augmented trabeculectomy is safe and effective as a treatment of primary or secondary pediatric glaucoma, with particularly encouraging results in cases of secondary glaucoma. Trabeculectomy offers the potential for delaying or avoiding glaucoma drainage device surgery in a significant proportion of children.

Associations of metabolic syndrome in SLE

ObjectivesTo characterise the prevalence and associations of metabolic syndrome (MetS) in a multiethnic cohort of patients with SLE.MethodsUsing a standardised protocol, baseline demographics, per visit disease activity (Systemic Lupus Erythematosus...

Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America.

There are limited long-term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)-treated women during pregnancy. To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post-partum in a low HBV endemic region. Retrospective real-world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post-partum. In 341 women (446 pregnancies) followed for a median of 33months (IQR: 26.7-39.5) post-partum, 19% (65/341) received TDF (11 initiated pre-pregnancy, 53 for mother-to-child transmission (MTCT) prevention). During follow-up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re-treated. In all TDF-treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow-up levels were 7.2, 3.0 and 5.5log IU/mL respectively [P<0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P=0.03), especially for those who stopped TDF post-partum, requiring re-treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post-partum ALT flare; one with fulminant hepatitis underwent transplant 13months post-partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30months (IQR: 23-40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17months (IQR: 12-26) post-partum. Post-partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long-term follow-up.

Abstract 4600: Germline homologous recombination deficiency pathway defects in a multi-ethnic East Asian, Southeast Asian and South Asian cancer patient cohort

Abstract Introduction There is limited diversity in current hereditary multi-gene testing data-sets, leading to greater challenges in accurate variant classification. To address this, a collaboration between 3 Singapore-based healthcare organizations (Tan Tock Seng Hospital, National Cancer Centre Singapore and Lucence Diagnostics) pooled results from patients of East Asian, Southeast Asian and South Asian ancestry, representing over 60% of the world's population. We hypothesized that a multi-ethnic collaboration would provide deeper understanding of cancer predisposition genes, particularly in terms of novel variants. Methods A total of 704 cancer patients of multi-ethnic Asian (SE Asian, East Asian and South Asian) ethnicity with either a history of breast, ovarian, pancreatic or prostate cancer, were tested with multi-gene panels. All patients were tested by multi-gene testing, including but not limited to BRCA1/2, PALB2 and ATM. In addition to genetic testing, the family histories of the patients were collected. All variants were classified by ACMG criteria. Chi-square testing was used for statistical analysis. Results Three sites (TTSH, NCCS, and Lucence) pooled patients selected for breast (n=458), ovarian (n=176), pancreatic (n=61) and prostate cancer (n=25). The mean and median ages were 44.9 years and 43 years, respectively. Of the 704 patients, 209 had a history of cancer in their first degree relatives, 432 did not and 63 patients did not know of any cancers in their first degree relatives. 122 of 704 patients (17.33%) had pathogenic/likely pathogenic variants in any tested risk-related gene, of which 86 were in BRCA1/2, 11 in PALB2 and 4 in ATM. Some variants were detected in more than one patient. 212 of 704 patients (30.1%) had VUSs detected in any tested risk-related gene, with 32.1% in BRCA1/2. There was a positive association between multiple-cancer status and pathogenic variants (9/22 vs 113/682, p = 0.007). Most notably, among the unique pathogenic/likely pathogenic variants in BRCA1, BRCA2, PALB2 and ATM, 10.64% (5/47), 12.9% (4/31), 30% (3/10) and 25% (1/4) respectively were novel variants, not previously reported in ClinVar (Dec 2019). Conclusion To our knowledge, this is the largest regional multi-ethnic cohort of patients with breast, ovarian, pancreatic and prostate cancer undergoing comprehensive genetic testing. Only one third of patients reported a first-degree family history suggesting that testing ought to be performed if clinical suspicion is high. Notably, 14.1% of BRCA1/BRCA2/PALB2/ATM pathogenic/likely pathogenic variants detected in our cohort were novel variants, not hitherto published in ClinVar. In conclusion, this collaboration demonstrates that testing of Asian patients can enrich global understanding of cancer predisposition gene mutations. This will improve cancer prevention, surveillance, and treatment selection for cancer patients, such as the use of PARP inhibitors for genetic defects of DNA repair. Citation Format: Jens Samol, Wei Lim Chia, Liuh Ling Goh, Matthew Myint, Min-Han Tan, Ru Jin Tay, Hao Chen, Yukti Choudhury, Ann SG Lee. Germline homologous recombination deficiency pathway defects in a multi-ethnic East Asian, Southeast Asian and South Asian cancer patient cohort [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4600.

Abstract 47: Using Ultrasound and Inflammation to Improve Prediction of Ischemic Stroke: A Secondary Analysis of MESA

Background: The Multi-Ethnic Study of Atherosclerosis (MESA) is a large prospective epidemiologic study of the clinical factors that can predict transition from asymptomatic to symptomatic cardiovascular disease. Although prior studies have looked at ischemic stroke, they have not systematically examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary stroke risk. Methods: The primary outcome is incident ischemic stroke during follow-up. The predictors are 9 ultrasound-derived measurements and 5 serum measurements related to inflammation. We fit Cox models to ischemic stroke and adjusted for patient age, hypertension, diabetes, total cholesterol, and smoking. Using DeLong’s method, we compared the AUC of the baseline adjusted model to the AUC of the model with predictor variables that were significant in the Cox models, to determine if they improved stroke prediction. Results: We included 6,095 patients with an average age of 61.9 years. The primary outcome of ischemic stroke was seen in 107 patients (1.8%) and the mean follow-up time was 7.7 years. In the Cox models, we found that small artery elasticity (SAE), carotid distensibility (CD), carotid stenosis (CS), and interleukin-6 (IL6) were associated with incident stroke. The AUC of the baseline model to predict stroke, which included patient age, hypertension, diabetes, total cholesterol, and smoking, was 0.745. When we added tertiles of SAE, CD, IL6 and categories of CS, the AUC improved to 0.765 (p=0.021 for difference). Conclusions: In a multiethnic cohort of patients without CVD at baseline, we found several ultrasound measurements and a serum marker of inflammation which predicted the occurrence of a primary ischemic stroke. Adding these basic ultrasound and serum measurements significantly improved the prediction of stroke, which could have implications for primary prevention efforts.

The long-term efficacy and safety of fluocinolone acetonide intravitreal implant 190 μg (ILUVIEN®) in diabetic macular oedema in a multi-ethnic inner-city population.

The purpose of this study is to report the long-term efficacy and safety of 0.19 mg fluocinolone acetonide intravitreal implant (ILUVIEN®) in pseudophakic eyes with diabetic macular oedema in a multi-ethnic patient cohort. This is a single-centre retrospective analysis of patients with persistent diabetic macular oedema, despite previous anti-vascular endothelial growth factor and/or steroid treatment, treated with the ILUVIEN implant according to national guidelines. Patients with follow-up of less than 24 months were excluded. Best corrected visual acuity, central retinal thickness and intraocular pressure were evaluated at baseline and month 3, 12, 24 and 36 post-treatment. A sub-group analysis was performed on eyes with 36-month follow-up data. In total, 24 eyes (24 patients) completed at least 24 months of follow-up, of which 9 completed 36 months of follow-up. Three-fourths of the patients were black or South Asian (blacks, Asians and minority ethnic). Improvement in mean best corrected visual acuity was seen at year 1 and year 3 improving from 0.62 LogMAR at baseline to 0.55 LogMAR at year 1 and 0.47 LogMAR at year 3 (all p > 0.05). Mean central retinal thickness also showed a progressive reduction from 471 μm at baseline to 397 μm at year 1 and 339 μm at year 3 (all p < 0.05). Four eyes required intraocular pressure-lowering drops post-implant. Supplementary treatment for persistent or recurrent diabetic macular oedema was necessary in 13 eyes over the total study period of 3 years. Blacks, Asians and minority ethnic patients had a worse response compared with white patients. The ILUVIEN implant was effective and safe in the treatment of multi-ethnic patients with diabetic macular oedema refractory to conventional therapies, improving the vision and macular anatomy, without significant adverse events up to 36 months post-treatment.

Effect of Warfarin on Ischemic Stroke, Bleeding, and Mortality in Patients with Atrial Fibrillation Receiving Peritoneal Dialysis.

There is limited information on the risks and benefits of anticoagulation in patients with atrial fibrillation receiving peritoneal dialysis. The aim was to determine the risk of mortality, ischemic stroke, and bleeding associated with warfarin use in patients with atrial fibrillation receiving peritoneal dialysis. This is a retrospective observational study of a multi-ethnic cohort of patients with atrial fibrillation receiving peritoneal dialysis in the United States. Using a dialysis registry, we identified 476 patients with atrial fibrillation receiving peritoneal dialysis. Among these patients, 115 (24%) were treated with warfarin. Cox proportional hazard models were used to compare risks of mortality, ischemic stroke and bleeding between the groups. Compared to untreated patients, patients receiving warfarin were older (67.3 ± 10.8 vs 62.9 ± 13.3years) and more likely to be white (42% vs 31%). Prevalence of comorbidities including hypertension, hyperlipidemia, diabetes, heart failure, and prior ischemic stroke were similar between the two groups. All cause mortality rates were 19.9 per 100 person-years in the warfarin group and 21.0 per 100 person-years in the untreated group. There was no difference between groups in the risk of mortality [hazard ratio (HR) 0.8, 95% confidence interval (CI) 0.53-1.2, p = 0.28], ischemic stroke (HR 2.3, 95% CI 0.94-5.4, p = 0.07), hemorrhagic stroke (HR 2.0, 95% CI 0.32-12.8, p = 0.46), gastrointestinal bleeding (HR 0.92, 95% CI 0.39-2.2, p = 0.86), or any bleeding (HR 1.2, 95% 0.60-2.3, p = 0.65). Even in the subgroup of patients with > 70% time in therapeutic range, no association was seen between warfarin treatment and mortality. There is no significant association between warfarin treatment with risks of mortality, ischemic stroke or bleeding in patients with atrial fibrillation receiving peritoneal dialysis.

A Missense Variant in PTPN22 is a Risk Factor for Drug-induced Liver Injury

We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings. We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P= 1.2× 10-9 and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P= .01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P= 4.0× 10-6; allele frequency= 13.3%), but the polymorphism was associated with DILI of other causes (OR1.37; 95% CI 1.21-1.56; P= 1.5× 10-6; allele frequency= 11.5%). Among amoxicillin- and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A*02:01 and DRB1*15:01. In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.

Efficacy of a Discharge Educational Strategy vs Standard Discharge Care on Reduction of Vascular Risk in Patients With Stroke and Transient Ischemic Attack

Despite secondary prevention strategies with proven efficacy, recurrent stroke rates remain high, particularly in racial/ethnic minority populations who are disproportionately affected by stroke. To determine the efficacy of a culturally tailored skills-based educational intervention with telephone follow-up compared with standard discharge care on systolic blood pressure reduction in a multiethnic cohort of patients with mild/moderate stroke/transient ischemic attack. Randomized clinical trial with 1-year follow-up. Participants were white, black, and Hispanic patients with mild/moderate stroke/transient ischemic attack prospectively enrolled from 4 New York City, New York, medical centers during hospitalization or emergency department visit between August 2012 and May 2016. Through screening of stroke admissions and emergency department notifications, 1083 eligible patients were identified, of whom 256 declined to participate and 275 were excluded for other reasons. Analyses were intention to treat. The Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) intervention is a skills-based, culturally tailored discharge program with follow-up calls delivered by a community health coordinator. This intervention was developed using a community engagement approach. The primary outcome was systolic blood pressure reduction at 12 months postdischarge. A total of 552 participants were randomized to receive intervention or usual care (281 women [51%]; mean [SD] age, 64.61 [2.9] years; 180 Hispanic [33%], 151 non-Hispanic white [27%], and 183 non-Hispanic black [33%]). At 1-year follow-up, no significant difference in systolic blood pressure reduction was observed between intervention and usual care groups (β = 2.5 mm Hg; 95% CI, -1.9 to 6.9). Although not powered for subgroup analysis, we found that among Hispanic individuals, the intervention arm had a clinically and statically significant 9.9 mm Hg-greater mean systolic blood pressure reduction compared with usual care (95% CI, 1.8-18.0). There were no significant differences between arms among non-Hispanic white (β = 3.3; 95% CI, -4.1 to 10.7) and non-Hispanic black participants (β = -1.6; 95% CI, -10.1 to 6.8). Few behavioral intervention studies in individuals who have had stroke have reported clinically meaningful reductions in blood pressure at 12 months, and fewer have focused on a skills-based approach. Results of secondary analyses suggest that culturally tailored, skills-based strategies may be an important alternative to knowledge-focused approaches in achieving sustained vascular risk reduction and addressing racial/ethnic stroke disparities; however, these findings should be tested in future studies. ClinicalTrials.gov identifier: NCT01836354.