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Publication Record


Association of ectopic fat with abdominal aorto-illiac and coronary artery calcification in african ancestry men.
Kuipers AL, Zmuda JM, Carr JJ, Terry JG, Nair S, Cvejkus R, Bunker CH, Patrick AL, Wassel CL, Miljkovic I
(2017) Atherosclerosis 263: 198-204
MeSH Terms: Absorptiometry, Photon, Adiposity, Adult, African Continental Ancestry Group, Aged, Aorta, Abdominal, Aortic Diseases, Aortography, Chi-Square Distribution, Computed Tomography Angiography, Coronary Angiography, Coronary Artery Disease, Humans, Iliac Artery, Intra-Abdominal Fat, Liver, Logistic Models, Male, Middle Aged, Muscle, Skeletal, Odds Ratio, Prospective Studies, Risk Factors, Trinidad and Tobago, Vascular Calcification
Show Abstract · Added September 11, 2017
BACKGROUND AND AIMS - There is strong evidence that fat accumulating in non-adipose sites, "ectopic fat", is associated with cardiovascular disease (CVD), including vascular calcification. Most previous studies of this association have assessed only a single ectopic fat depot. Therefore, our aim was to assess the association of total, regional, and ectopic fat with abdominal aorto-illiac calcification (AAC) and coronary artery calcification (CAC) in 798 African ancestry men.
METHODS - Participants (mean age 62) were from the Tobago Bone Health Study cohort. Adiposity was assessed via clinical examination, dual x-ray absorptiometry, and computed tomography (CT). Ectopic fat depots included: abdominal visceral adipose tissue (VAT), liver attenuation, and calf intermuscular adipose tissue (IMAT). Vascular calcification was assessed by CT and quantified as present versus absent. Associations were tested using multiple logistic regression adjusted for traditional cardiovascular risk factors. Models of ectopic fat were additionally adjusted for total body fat and standing height.
RESULTS - All adiposity measures, except VAT, were associated with AAC. Lower liver attenuation or greater calf IMAT was associated with 1.2-1.3-fold increased odds of AAC (p < 0.03 for both), though calf IMAT was a stronger predictor than liver attenuation (p < 0.001) when entered in a single model. No ectopic fat measure was associated with CAC.
CONCLUSIONS - Greater adiposity in the skeletal muscle and liver, but not in the visceral compartment, was associated with increased odds of AAC in African ancestry men. These results highlight the potential importance of both quantity and location of adiposity accumulation throughout the body.
Copyright © 2017 Elsevier B.V. All rights reserved.
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25 MeSH Terms
Admixture mapping of pelvic organ prolapse in African Americans from the Women's Health Initiative Hormone Therapy trial.
Giri A, Hartmann KE, Aldrich MC, Ward RM, Wu JM, Park AJ, Graff M, Qi L, Nassir R, Wallace RB, O'Sullivan MJ, North KE, Velez Edwards DR, Edwards TL
(2017) PLoS One 12: e0178839
MeSH Terms: Actins, African Americans, Aged, Body Mass Index, Case-Control Studies, Cystocele, European Continental Ancestry Group, Female, GPI-Linked Proteins, Gene Expression, Humans, Logistic Models, Middle Aged, Molecular Chaperones, Nerve Tissue Proteins, Odds Ratio, Parity, Quantitative Trait Loci, Quantitative Trait, Heritable, Rectocele, Risk Factors, Severity of Illness Index, United States, Uterine Prolapse, Women's Health
Show Abstract · Added February 21, 2019
Evidence suggests European American (EA) women have two- to five-fold increased odds of having pelvic organ prolapse (POP) when compared with African American (AA) women. However, the role of genetic ancestry in relation to POP risk is not clear. Here we evaluate the association between genetic ancestry and POP in AA women from the Women's Health Initiative Hormone Therapy trial. Women with grade 1 or higher classification, and grade 2 or higher classification for uterine prolapse, cystocele or rectocele at baseline or during follow-up were considered to have any POP (N = 805) and moderate/severe POP (N = 156), respectively. Women with at least two pelvic exams with no indication for POP served as controls (N = 344). We performed case-only, and case-control admixture-mapping analyses using multiple logistic regression while adjusting for age, BMI, parity and global ancestry. We evaluated the association between global ancestry and POP using multiple logistic regression. European ancestry at the individual level was not associated with POP risk. Case-only and case-control local ancestry analyses identified two ancestry-specific loci that may be associated with POP. One locus (Chromosome 15q26.2) achieved empirically-estimated statistical significance and was associated with decreased POP odds (considering grade ≥2 POP) with each unit increase in European ancestry (OR: 0.35; 95% CI: 0.30, 0.57; p-value = 1.48x10-5). This region includes RGMA, a potent regulator of the BMP family of genes. The second locus (Chromosome 1q42.1-q42.3) was associated with increased POP odds with each unit increase in European ancestry (Odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28, 2.22; p-value = 1.93x10-4). Although this region did not reach statistical significance after considering multiple comparisons, it includes potentially relevant genes including TBCE, and ACTA1. Unique non-overlapping European and African ancestry-specific susceptibility loci may be associated with increased POP risk.
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Isoniazid-monoresistant tuberculosis is associated with poor treatment outcomes in Durban, South Africa.
van der Heijden YF, Karim F, Mufamadi G, Zako L, Chinappa T, Shepherd BE, Maruri F, Moosa MS, Sterling TR, Pym AS
(2017) Int J Tuberc Lung Dis 21: 670-676
MeSH Terms: Adult, Antitubercular Agents, Drug Resistance, Bacterial, Female, HIV Infections, Humans, Isoniazid, Logistic Models, Longitudinal Studies, Male, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Retrospective Studies, South Africa, Treatment Failure, Treatment Outcome, Tuberculosis
Show Abstract · Added March 14, 2018
SETTING - A large tuberculosis (TB) clinic in Durban, South Africa.
OBJECTIVE - To determine the association between isoniazid (INH) monoresistant TB and treatment outcomes.
DESIGN - We performed a retrospective longitudinal study of patients seen from 2000 to 2012 to compare episodes of INH-monoresistant TB with those of drug-susceptible TB using logistic regression with robust standard errors. INH-monoresistant TB was treated with modified regimens.
RESULTS - Among 18 058 TB patients, there were 19 979 TB episodes for which drug susceptibility testing was performed. Of these, 557 were INH-monoresistant and 16 311 were drug-susceptible. Loss to follow-up, transfer, and human immunodeficiency virus (HIV) co-infection (41% had known HIV status) were similar between groups. INH-monoresistant episodes were more likely to result in treatment failure (4.1% vs. 0.6%, P < 0.001) and death (3.2% vs. 1.8%, P = 0.01) than drug-susceptible episodes. After adjustment for age, sex, race, retreatment status, and disease site, INH-monoresistant episodes were more likely to have resulted in treatment failure (OR 6.84, 95%CI 4.29-10.89, P < 0.001) and death (OR 1.81, 95%CI 1.11-2.95, P = 0.02).
CONCLUSION - INH monoresistance was associated with worse clinical outcomes than drug-susceptible TB. Our findings support the need for rapid diagnostic tests for INH resistance and improved treatment regimens for INH-monoresistant TB.
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17 MeSH Terms
Calibration drift in regression and machine learning models for acute kidney injury.
Davis SE, Lasko TA, Chen G, Siew ED, Matheny ME
(2017) J Am Med Inform Assoc 24: 1052-1061
MeSH Terms: Acute Kidney Injury, Aged, Bayes Theorem, Clinical Decision-Making, Decision Support Techniques, Female, Hospitals, Veterans, Humans, Logistic Models, Machine Learning, Male, Middle Aged, United States
Show Abstract · Added April 7, 2017
Objective - Predictive analytics create opportunities to incorporate personalized risk estimates into clinical decision support. Models must be well calibrated to support decision-making, yet calibration deteriorates over time. This study explored the influence of modeling methods on performance drift and connected observed drift with data shifts in the patient population.
Materials and Methods - Using 2003 admissions to Department of Veterans Affairs hospitals nationwide, we developed 7 parallel models for hospital-acquired acute kidney injury using common regression and machine learning methods, validating each over 9 subsequent years.
Results - Discrimination was maintained for all models. Calibration declined as all models increasingly overpredicted risk. However, the random forest and neural network models maintained calibration across ranges of probability, capturing more admissions than did the regression models. The magnitude of overprediction increased over time for the regression models while remaining stable and small for the machine learning models. Changes in the rate of acute kidney injury were strongly linked to increasing overprediction, while changes in predictor-outcome associations corresponded with diverging patterns of calibration drift across methods.
Conclusions - Efficient and effective updating protocols will be essential for maintaining accuracy of, user confidence in, and safety of personalized risk predictions to support decision-making. Model updating protocols should be tailored to account for variations in calibration drift across methods and respond to periods of rapid performance drift rather than be limited to regularly scheduled annual or biannual intervals.
© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com
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13 MeSH Terms
An Empirical Study for Impacts of Measurement Errors on EHR based Association Studies.
Duan R, Cao M, Wu Y, Huang J, Denny JC, Xu H, Chen Y
(2016) AMIA Annu Symp Proc 2016: 1764-1773
MeSH Terms: Computer Simulation, Disease, Electronic Health Records, Genome-Wide Association Study, Genotype, Hospital Administration, Humans, Logistic Models, Medical Errors
Show Abstract · Added March 14, 2018
Over the last decade, Electronic Health Records (EHR) systems have been increasingly implemented at US hospitals. Despite their great potential, the complex and uneven nature of clinical documentation and data quality brings additional challenges for analyzing EHR data. A critical challenge is the information bias due to the measurement errors in outcome and covariates. We conducted empirical studies to quantify the impacts of the information bias on association study. Specifically, we designed our simulation studies based on the characteristics of the Electronic Medical Records and Genomics (eMERGE) Network. Through simulation studies, we quantified the loss of power due to misclassifications in case ascertainment and measurement errors in covariate status extraction, with respect to different levels of misclassification rates, disease prevalence, and covariate frequencies. These empirical findings can inform investigators for better understanding of the potential power loss due to misclassification and measurement errors under a variety of conditions in EHR based association studies.
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9 MeSH Terms
Urinary retention and catheter use among U.S. female Medicare beneficiaries: Prevalence and risk factors.
Cohn JA, Ni S, Kaufman MR, Graves AJ, Penson DF, Dmochowski RR, Reynolds WS
(2017) Neurourol Urodyn 36: 2101-2108
MeSH Terms: Aged, Aged, 80 and over, Case-Control Studies, Female, Humans, Logistic Models, Medicare, Multivariate Analysis, Nervous System Diseases, Pelvic Organ Prolapse, Prevalence, Risk Factors, United States, Urinary Catheterization, Urinary Retention, Urinary Tract Infections
Show Abstract · Added September 16, 2019
AIMS - To identify the prevalence of and risk factors for urinary retention and catheterization among female Medicare beneficiaries.
METHODS - We identified women with a diagnosis of urinary retention in a 5% sample of Medicare claims in 2012. Women were categorized into three groups based on the occurrence and duration of urinary catheterization within a 1 year period: 1) no catheterization; 2) short-term catheterization (ie, one or more catheterizations in less than 30 days); and 3) chronic catheterization (catheterizations in multiple 30 day periods within 1 year). We then identified a group of age-matched controls without catheterization or a diagnosis of urinary retention in 2012. Clinical and demographic data were collected for each patient, and risk factors for retention and catheterization were compared across groups. We assessed factors associated with urinary retention using multivariable logistic regression.
RESULTS - We estimated the rate of retention to be 1532 per 100 000 U.S. female Medicare beneficiaries in 2012, with rates of short term and chronic catheterization estimated to be 160 and 108 per 100 000 women, respectively. Prior diagnoses of neurologic condition, urinary tract infection, and pelvic organ prolapse were positively associated with retention and catheterization in multivariable analyses.
CONCLUSIONS - We estimated the prevalence of urinary retention diagnoses among female Medicare beneficiaries to be 1532 per 100 000 women. Retention and catheterization were significantly associated with comorbid disease, with the strongest associations identified with a concomitant diagnosis of neurologic condition, UTI, and POP.
© 2017 Wiley Periodicals, Inc.
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Relation of Obstructive Sleep Apnea and a Common Variant at Chromosome 4q25 to Atrial Fibrillation.
Patel NJ, Wells QS, Huang S, Upender RP, Darbar D, Monahan K
(2017) Am J Cardiol 119: 1387-1391
MeSH Terms: Aged, Aged, 80 and over, Atrial Fibrillation, Case-Control Studies, Chromosomes, Human, Pair 4, Electrocardiography, Female, Genetic Predisposition to Disease, Genotype, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Polymorphism, Single Nucleotide, Polysomnography, Risk Factors, Severity of Illness Index, Sleep Apnea, Obstructive
Show Abstract · Added April 6, 2017
Obstructive sleep apnea (OSA) and single nucleotide polymorphisms (SNPs) at the 4q25 locus are associated with increased risk of atrial fibrillation (AF). Whether these associations are independent of traditional risk factors for AF remains unknown. Using billing code queries and manual chart review, we assembled a cohort of adults that underwent overnight polysomnography and at least 1 12-lead electrocardiogram. Case status was defined by electrocardiographic data in support of AF or documentation of AF by a staff cardiologist. Controls were defined by a lack of primary evidence of AF and absence of a diagnosis of AF in the medical record. OSA severity was categorized based on Apnea-Hypopnea Index. Genotyping for a key 4q25 SNP (rs2200733) was performed using the Sequenom platform. Logistic regression was used to test for associations of AF with OSA category and 4q25 SNP genotype while adjusting for age, gender, body mass index, ancestry, hypertension status, and heart failure status. The cohort consisted of 674 subjects (62 ± 13 years; 44% women), including 132 patients with AF. After adjustment for established risk factors, the association between AF and OSA severity was borderline significant (odds ratio 1.2, 95% CI 1.0 to 1.5). The association between AF and 4q25 SNP status remained significant in a fully adjusted model that included OSA severity (odds ratio 1.5, 95% CI 1.3 to 5.7). In conclusion, OSA severity and the chromosome 4q25 SNP genotype were associated with AF status independent of clinical risk factors. Knowledge of AF-related SNPs may enhance AF risk stratification for those undergoing polysomnography.
Copyright © 2017 Elsevier Inc. All rights reserved.
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19 MeSH Terms
Mitochondrial Haplogroups Affect Severity But Not Prevalence of Diabetic Retinopathy.
Bregman JA, Herren DJ, Estopinal CB, Chocron IM, Harlow PA, Warden C, Brantley MA, Samuels DC
(2017) Invest Ophthalmol Vis Sci 58: 1346-1351
MeSH Terms: Aged, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Diabetic Retinopathy, European Continental Ancestry Group, Female, Glycated Hemoglobin A, Haplotypes, Humans, Logistic Models, Male, Middle Aged, Mitochondria, Prevalence, Risk Factors, Severity of Illness Index, United Kingdom
Show Abstract · Added March 21, 2018
Purpose - We previously reported European mitochondrial haplogroup H to be a risk factor for and haplogroup UK to be protective against proliferative diabetic retinopathy (PDR) among Caucasian patients with diabetic retinopathy (DR). The purpose of this study was to determine whether these haplogroups are also associated with the risk of having DR among Caucasian patients with diabetes.
Methods - Deidentified medical records for 637 Caucasian patients with diabetes (223 with DR) were obtained from BioVU, Vanderbilt University's electronic, deidentified DNA databank. An additional 197 Caucasian patients with diabetes (98 with DR) were enrolled from the Vanderbilt Eye Institute (VEI). We tested for an association between European mitochondrial haplogroups and DR status.
Results - The percentage of diabetes patients with DR did not differ across the haplogroups (P = 0.32). The percentage of patients with nonproliferative DR (NPDR; P = 0.0084) and with PDR (P = 0.027) significantly differed across the haplogroups. In logistic regressions adjusting for sex, age, diabetes type, duration of diabetes, and hemoglobin A1c, neither haplogroup H nor haplogroup UK had a significant effect on DR compared with diabetic controls. Haplogroup UK was a significant risk factor (OR = 1.72 [1.13-2.59], P = 0.010) for NPDR compared with diabetic controls in the unadjusted analysis, but not in the adjusted analysis (OR = 1.29 [0.79-2.10], P = 0.20).
Conclusions - Mitochondrial haplogroups H and UK were associated with severity, but not presence, of DR. These data argue that the effect of these haplogroups is related to ischemia and neovascularization, the defining features of PDR.
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17 MeSH Terms
Identification of unique venous thromboembolism-susceptibility variants in African-Americans.
Heit JA, Armasu SM, McCauley BM, Kullo IJ, Sicotte H, Pathak J, Chute CG, Gottesman O, Bottinger EP, Denny JC, Roden DM, Li R, Ritchie MD, de Andrade M
(2017) Thromb Haemost 117: 758-768
MeSH Terms: Adult, African Americans, Aged, Biological Specimen Banks, Case-Control Studies, Databases, Genetic, Electronic Health Records, Female, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Logistic Models, Male, Middle Aged, Odds Ratio, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Sex Factors, United States, Venous Thromboembolism
Show Abstract · Added March 14, 2018
To identify novel single nucleotide polymorphisms (SNPs) associated with venous thromboembolism (VTE) in African-Americans (AAs), we performed a genome-wide association study (GWAS) of VTE in AAs using the Electronic Medical Records and Genomics (eMERGE) Network, comprised of seven sites each with DNA biobanks (total ~39,200 unique DNA samples) with genome-wide SNP data (imputed to 1000 Genomes Project cosmopolitan reference panel) and linked to electronic health records (EHRs). Using a validated EHR-driven phenotype extraction algorithm, we identified VTE cases and controls and tested for an association between each SNP and VTE using unconditional logistic regression, adjusted for age, sex, stroke, site-platform combination and sickle cell risk genotype. Among 393 AA VTE cases and 4,941 AA controls, three intragenic SNPs reached genome-wide significance: LEMD3 rs138916004 (OR=3.2; p=1.3E-08), LY86 rs3804476 (OR=1.8; p=2E-08) and LOC100130298 rs142143628 (OR=4.5; p=4.4E-08); all three SNPs validated using internal cross-validation, parametric bootstrap and meta-analysis methods. LEMD3 rs138916004 and LOC100130298 rs142143628 are only present in Africans (1000G data). LEMD3 showed a significant differential expression in both NCBI Gene Expression Omnibus (GEO) and the Mayo Clinic gene expression data, LOC100130298 showed a significant differential expression only in the GEO expression data, and LY86 showed a significant differential expression only in the Mayo expression data. LEMD3 encodes for an antagonist of TGF-β-induced cell proliferation arrest. LY86 encodes for MD-1 which down-regulates the pro-inflammatory response to lipopolysaccharide; LY86 variation was previously associated with VTE in white women; LOC100130298 is a non-coding RNA gene with unknown regulatory activity in gene expression and epigenetics.
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21 MeSH Terms
Comparison of the AJCC, MSTS, and Modified Spanier Systems for Clinical and Pathologic Staging of Osteosarcoma.
Cates JM
(2017) Am J Surg Pathol 41: 405-413
MeSH Terms: Adult, Aged, Bone Neoplasms, Female, Follow-Up Studies, Humans, Logistic Models, Male, Middle Aged, Neoplasm Staging, Osteosarcoma, Prognosis, Retrospective Studies, Survival Analysis
Show Abstract · Added November 1, 2018
The prognostic performance of the 2 most commonly used staging systems for skeletal sarcoma (the American Joint Committee on Cancer [AJCC] and Musculoskeletal Tumor Society [MSTS] systems) have never been compared analytically. Another staging system originally proposed by Spanier has not yet been validated. Given the recent release of the 8th edition of the AJCC Cancer Staging Manual, this study was designed to directly compare these anatomic staging systems in a series of 153 high-grade, intramedullary osteosarcomas. Kaplan-Meier curves were plotted and pairwise comparisons between each stage category were performed. Predictive accuracy of each staging system for determining 5-year disease-free survival was evaluated by comparing areas under receiver-operating characteristic curves generated from logistic regression analysis. Multiple concordance indices were calculated using bootstrapping methods (200 replications). ρk and R were estimated as measures of the variation in survival outcomes explained by the regression models. The AJCC, MSTS, and a modified version of the Spanier staging systems showed similar discriminatory abilities and no significant differences in the levels of contrast between different tumor stages across staging systems. Addition of T-category information from each staging system contributed significant prognostic information compared with a Cox proportional hazard regression model consisting only of the presence or absence of metastatic disease as a measure of disease extent. Concordance indices and predictive accuracy for 5-year disease-free survival were not significantly different among the different staging systems either. Similar findings were observed after accounting for other important prognostic variables. Additional studies are necessary to determine performance parameters of each staging system for other types of skeletal sarcoma. Prognostic performance of osteosarcoma staging systems would also be improved by incorporating nonanatomic prognostic variables into staging algorithms.
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