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Viewing the Future of IR through Molecular Histology: An Overview of Imaging Mass Spectrometry.
Cressman ENK, Spraggins JM
(2018) J Vasc Interv Radiol 29: 1543-1546.e1
MeSH Terms: Diffusion of Innovation, Forecasting, Humans, Molecular Imaging, Predictive Value of Tests, Radiology, Interventional, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Added March 26, 2019
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7 MeSH Terms
Validation of discharge diagnosis codes to identify serious infections among middle age and older adults.
Wiese AD, Griffin MR, Stein CM, Schaffner W, Greevy RA, Mitchel EF, Grijalva CG
(2018) BMJ Open 8: e020857
MeSH Terms: Aged, Aged, 80 and over, Algorithms, Clinical Coding, Female, Humans, Infection, International Classification of Diseases, Male, Medicaid, Medical Records, Middle Aged, Patient Discharge, Predictive Value of Tests, Reproducibility of Results, Retrospective Studies, Tennessee, United States
Show Abstract · Added July 27, 2018
OBJECTIVES - Hospitalisations for serious infections are common among middle age and older adults and frequently used as study outcomes. Yet, few studies have evaluated the performance of diagnosis codes to identify serious infections in this population. We sought to determine the positive predictive value (PPV) of diagnosis codes for identifying hospitalisations due to serious infections among middle age and older adults.
SETTING AND PARTICIPANTS - We identified hospitalisations for possible infection among adults >=50 years enrolled in the Tennessee Medicaid healthcare programme (2008-2012) using International Classifications of Diseases, Ninth Revision diagnosis codes for pneumonia, meningitis/encephalitis, bacteraemia/sepsis, cellulitis/soft-tissue infections, endocarditis, pyelonephritis and septic arthritis/osteomyelitis.
DESIGN - Medical records were systematically obtained from hospitals randomly selected from a stratified sampling framework based on geographical region and hospital discharge volume.
MEASURES - Two trained clinical reviewers used a standardised extraction form to abstract information from medical records. Predefined algorithms served as reference to adjudicate confirmed infection-specific hospitalisations. We calculated the PPV of diagnosis codes using confirmed hospitalisations as reference. Sensitivity analyses determined the robustness of the PPV to definitions that required radiological or microbiological confirmation. We also determined inter-rater reliability between reviewers.
RESULTS - The PPV of diagnosis codes for hospitalisations for infection (n=716) was 90.2% (95% CI 87.8% to 92.2%). The PPV was highest for pneumonia (96.5% (95% CI 93.9% to 98.0%)) and cellulitis (91.1% (95% CI 84.7% to 94.9%)), and lowest for meningitis/encephalitis (50.0% (95% CI 23.7% to 76.3%)). The adjudication reliability was excellent (92.7% agreement; first agreement coefficient: 0.91). The overall PPV was lower when requiring microbiological confirmation (45%) and when requiring radiological confirmation for pneumonia (79%).
CONCLUSIONS - Discharge diagnosis codes have a high PPV for identifying hospitalisations for common, serious infections among middle age and older adults. PPV estimates for rare infections were imprecise.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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18 MeSH Terms
Validation of an algorithm to identify heart failure hospitalisations in patients with diabetes within the veterans health administration.
Presley CA, Min JY, Chipman J, Greevy RA, Grijalva CG, Griffin MR, Roumie CL
(2018) BMJ Open 8: e020455
MeSH Terms: Adult, Aged, Algorithms, Diabetes Complications, Diabetes Mellitus, Diagnosis-Related Groups, Female, Heart Failure, Hospitalization, Humans, International Classification of Diseases, Male, Middle Aged, Predictive Value of Tests, Sensitivity and Specificity, Veterans
Show Abstract · Added July 27, 2018
OBJECTIVES - We aimed to validate an algorithm using both primary discharge diagnosis (International Classification of Diseases Ninth Revision (ICD-9)) and diagnosis-related group (DRG) codes to identify hospitalisations due to decompensated heart failure (HF) in a population of patients with diabetes within the Veterans Health Administration (VHA) system.
DESIGN - Validation study.
SETTING - Veterans Health Administration-Tennessee Valley Healthcare System PARTICIPANTS: We identified and reviewed a stratified, random sample of hospitalisations between 2001 and 2012 within a single VHA healthcare system of adults who received regular VHA care and were initiated on an antidiabetic medication between 2001 and 2008. We sampled 500 hospitalisations; 400 hospitalisations that fulfilled algorithm criteria, 100 that did not. Of these, 497 had adequate information for inclusion. The mean patient age was 66.1 years (SD 11.4). Majority of patients were male (98.8%); 75% were white and 20% were black.
PRIMARY AND SECONDARY OUTCOME MEASURES - To determine if a hospitalisation was due to HF, we performed chart abstraction using Framingham criteria as the referent standard. We calculated the positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for the overall algorithm and each component (primary diagnosis code (ICD-9), DRG code or both).
RESULTS - The algorithm had a PPV of 89.7% (95% CI 86.8 to 92.7), NPV of 93.9% (89.1 to 98.6), sensitivity of 45.1% (25.1 to 65.1) and specificity of 99.4% (99.2 to 99.6). The PPV was highest for hospitalisations that fulfilled both the ICD-9 and DRG algorithm criteria (92.1% (89.1 to 95.1)) and lowest for hospitalisations that fulfilled only DRG algorithm criteria (62.5% (28.4 to 96.6)).
CONCLUSIONS - Our algorithm, which included primary discharge diagnosis and DRG codes, demonstrated excellent PPV for identification of hospitalisations due to decompensated HF among patients with diabetes in the VHA system.
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
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16 MeSH Terms
Modeling Continuous Prognostic Factors in Survival Analysis: Implications for Tumor Staging and Assessing Chemotherapy Effect in Osteosarcoma.
Cates JMM
(2018) Am J Surg Pathol 42: 485-491
MeSH Terms: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Bone Neoplasms, Chemotherapy, Adjuvant, Child, Databases, Factual, Decision Support Techniques, Female, Humans, Male, Middle Aged, Models, Statistical, Necrosis, Neoadjuvant Therapy, Neoplasm Staging, Orthopedic Procedures, Osteosarcoma, Predictive Value of Tests, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Tumor Burden, United States, Young Adult
Show Abstract · Added November 1, 2018
Extent of response to neoadjuvant chemotherapy, tumor size, and patient age are important prognostic variables for patients with osteosarcoma, but applying information from these continuous variables in survival models is difficult. Dichotomization is usually inappropriate and alternative statistical techniques should be considered instead. Nonlinear multivariable regression methods (restricted cubic splines and fractional polynomials) were applied to data from the National Cancer Database to model continuous prognostic factors for overall survival from localized, high-grade osteosarcoma of the appendicular and nonspinal skeleton following neoadjuvant chemotherapy and surgical resection (N=2493). The assumption that log hazard ratios were linear in relation to these continuous prognostic factors was tested using likelihood ratio tests of model deviance and Wald tests of spline coefficients. Log hazard ratios for increasing patient age were linear over the range of 4 to 80 years, but showed evidence for variation in the coefficient over elapsed follow-up time. Tumor size also showed a linear relationship with log hazard over the range of 1 to 30 cm. Hazard ratios for chemotherapy effect profoundly deviated from log-linear (P<0.004), with significantly decreased hazard for death from baseline for patients with ≥90% tumor necrosis (hazard ratio, 0.32; 95% confidence interval, 0.20-0.52; P<0.0001). Important implications of these results include: (1) ≥90% tumor necrosis defines good chemotherapy response in a clinically useful manner; (2) staging osteosarcoma by dichotomizing tumor size is inappropriate; and (3) patient age can be modeled as a linear effect on the log hazard ratio in prognostic models with the caveat that risk may change over duration of the analysis.
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28 MeSH Terms
Research Directions in Genetic Predispositions to Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis.
Manolio TA, Hutter CM, Avigan M, Cibotti R, Davis RL, Denny JC, Grenade L, Wheatley LM, Carrington MN, Chantratita W, Chung WH, Dalton AD, Hung SI, Lee MTM, Leeder JS, Lertora JJL, Mahasirimongkol S, McLeod HL, Mockenhaupt M, Pacanowski M, Phillips EJ, Pinheiro S, Pirmohamed M, Sung C, Suwankesawong W, Trepanier L, Tumminia SJ, Veenstra D, Yuliwulandari R, Shear NH
(2018) Clin Pharmacol Ther 103: 390-394
MeSH Terms: Genetic Predisposition to Disease, Genetic Testing, Humans, Incidence, Necrosis, Predictive Value of Tests, Stevens-Johnson Syndrome
Show Abstract · Added March 14, 2018
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is one of the most devastating of adverse drug reactions (ADRs) and was, until recently, essentially unpredictable. With the discovery of several risk alleles for drug-induced SJS/TEN and the demonstration of effectiveness of screening in reducing incidence, the stage is set for implementation of preventive strategies in populations at risk. Yet much remains to be learned about this potentially fatal complication of commonly used drugs.
© 2017 American Society for Clinical Pharmacology and Therapeutics.
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Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.
Cavallari LH, Lee CR, Beitelshees AL, Cooper-DeHoff RM, Duarte JD, Voora D, Kimmel SE, McDonough CW, Gong Y, Dave CV, Pratt VM, Alestock TD, Anderson RD, Alsip J, Ardati AK, Brott BC, Brown L, Chumnumwat S, Clare-Salzler MJ, Coons JC, Denny JC, Dillon C, Elsey AR, Hamadeh IS, Harada S, Hillegass WB, Hines L, Horenstein RB, Howell LA, Jeng LJB, Kelemen MD, Lee YM, Magvanjav O, Montasser M, Nelson DR, Nutescu EA, Nwaba DC, Pakyz RE, Palmer K, Peterson JF, Pollin TI, Quinn AH, Robinson SW, Schub J, Skaar TC, Smith DM, Sriramoju VB, Starostik P, Stys TP, Stevenson JM, Varunok N, Vesely MR, Wake DT, Weck KE, Weitzel KW, Wilke RA, Willig J, Zhao RY, Kreutz RP, Stouffer GA, Empey PE, Limdi NA, Shuldiner AR, Winterstein AG, Johnson JA, IGNITE Network
(2018) JACC Cardiovasc Interv 11: 181-191
MeSH Terms: Aged, Clinical Decision-Making, Clopidogrel, Cytochrome P-450 CYP2C19, Drug Resistance, Female, Humans, Male, Middle Aged, Patient Selection, Percutaneous Coronary Intervention, Pharmacogenetics, Pharmacogenomic Testing, Pharmacogenomic Variants, Platelet Aggregation Inhibitors, Prasugrel Hydrochloride, Predictive Value of Tests, Risk Assessment, Risk Factors, Ticagrelor, Time Factors, Treatment Outcome, United States
Show Abstract · Added March 14, 2018
OBJECTIVES - This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI).
BACKGROUND - CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI.
METHODS - After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights.
RESULTS - Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60).
CONCLUSIONS - These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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23 MeSH Terms
Predicting the Functional Impact of KCNQ1 Variants of Unknown Significance.
Li B, Mendenhall JL, Kroncke BM, Taylor KC, Huang H, Smith DK, Vanoye CG, Blume JD, George AL, Sanders CR, Meiler J
(2017) Circ Cardiovasc Genet 10:
MeSH Terms: Databases, Genetic, Female, Genetic Variation, Humans, KCNQ1 Potassium Channel, Long QT Syndrome, Male, Predictive Value of Tests, Protein Domains
Show Abstract · Added March 14, 2018
BACKGROUND - An emerging standard-of-care for long-QT syndrome uses clinical genetic testing to identify genetic variants of the KCNQ1 potassium channel. However, interpreting results from genetic testing is confounded by the presence of variants of unknown significance for which there is inadequate evidence of pathogenicity.
METHODS AND RESULTS - In this study, we curated from the literature a high-quality set of 107 functionally characterized KCNQ1 variants. Based on this data set, we completed a detailed quantitative analysis on the sequence conservation patterns of subdomains of KCNQ1 and the distribution of pathogenic variants therein. We found that conserved subdomains generally are critical for channel function and are enriched with dysfunctional variants. Using this experimentally validated data set, we trained a neural network, designated Q1VarPred, specifically for predicting the functional impact of KCNQ1 variants of unknown significance. The estimated predictive performance of Q1VarPred in terms of Matthew's correlation coefficient and area under the receiver operating characteristic curve were 0.581 and 0.884, respectively, superior to the performance of 8 previous methods tested in parallel. Q1VarPred is publicly available as a web server at http://meilerlab.org/q1varpred.
CONCLUSIONS - Although a plethora of tools are available for making pathogenicity predictions over a genome-wide scale, previous tools fail to perform in a robust manner when applied to KCNQ1. The contrasting and favorable results for Q1VarPred suggest a promising approach, where a machine-learning algorithm is tailored to a specific protein target and trained with a functionally validated data set to calibrate informatics tools.
© 2017 American Heart Association, Inc.
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9 MeSH Terms
Human papillomavirus 16 E6 antibodies are sensitive for human papillomavirus-driven oropharyngeal cancer and are associated with recurrence.
Lang Kuhs KA, Kreimer AR, Trivedi S, Holzinger D, Pawlita M, Pfeiffer RM, Gibson SP, Schmitt NC, Hildesheim A, Waterboer T, Ferris RL
(2017) Cancer 123: 4382-4390
MeSH Terms: Antibodies, Viral, Cell Transformation, Viral, Female, Human papillomavirus 16, Humans, Immunohistochemistry, Male, Middle Aged, Oncogene Proteins, Viral, Oropharyngeal Neoplasms, Papillomavirus Infections, Predictive Value of Tests, Prognosis, Recurrence, Repressor Proteins, Sensitivity and Specificity
Show Abstract · Added October 23, 2017
BACKGROUND - Human papillomavirus 16 (HPV16) E6 antibodies may be an early marker of the diagnosis and recurrence of human papillomavirus-driven oropharyngeal cancer (HPV-OPC).
METHODS - This study identified 161 incident oropharyngeal cancer (OPC) cases diagnosed at the University of Pittsburgh (2003-2013) with pretreatment serum. One hundred twelve had preexisting clinical HPV testing with p16 immunohistochemistry and HPV in situ hybridization (87 were dual-positive [HPV-OPC], and 25 were dual-negative [HPV-negative]); 62 had at least 1 posttreatment serum sample. Eighty-six of the 161 tumors were available for additional HPV16 DNA/RNA testing (45 were dual-positive [HPV16-OPC], and 19 were dual-negative [HPV16-negative). HPV16 E6 antibody testing was conducted with multiplex serology. The following were evaluated: 1) the sensitivity and specificity of HPV16 E6 serology for distinguishing HPV-OPC and HPV16-OPC from HPV-negative OPC, 2) HPV16 E6 antibody decay after treatment with linear models accommodating correlations in variance estimates, and 3) pre- and posttreatment HPV16 E6 levels and the risk of recurrence with Cox proportional hazards models.
RESULTS - Seventy-eight of 87 HPV-OPCs were HPV16 E6-seropositive (sensitivity, 89.7%; 95% confidence interval [CI], 81.3%-95.2%), and 24 of 25 HPV-negative OPCs were HPV16 E6-seronegative (specificity, 96.0%; 95% CI, 79.6%-99.9%). Forty-two of 45 HPV16-OPCs were HPV16 E6-seropositive (sensitivity, 93.3%; 95% CI, 81.7%-98.6%), and 18 of 19 HPV16-negative OPCs were HPV16 E6-seronegative (specificity, 94.7%; 95% CI, 74.0%-99.9%). Posttreatment HPV16 E6 antibody levels did not decrease significantly from the baseline (P = .575; median follow-up, 307 days) and were not associated with the risk of recurrence. However, pretreatment HPV16 E6 seropositivity was associated with an 86% reduced risk of local/regional recurrence (hazard ratio, 0.14; 95% CI, 0.03-0.68; P = .015).
CONCLUSIONS - HPV16 E6 antibodies may have potential clinical utility for the diagnosis and/or prognosis of HPV-OPC. Cancer 2017;123:4382-90. © 2017 American Cancer Society.
© 2017 American Cancer Society.
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16 MeSH Terms
Evaluating the American College of Surgeons National Surgical Quality Improvement project risk calculator: results from the U.S. Extrahepatic Biliary Malignancy Consortium.
Beal EW, Lyon E, Kearney J, Wei L, Ethun CG, Black SM, Dillhoff M, Salem A, Weber SM, Tran TB, Poultsides G, Shenoy R, Hatzaras I, Krasnick B, Fields RC, Buttner S, Scoggins CR, Martin RCG, Isom CA, Idrees K, Mogal HD, Shen P, Maithel SK, Pawlik TM, Schmidt CR
(2017) HPB (Oxford) 19: 1104-1111
MeSH Terms: Academic Medical Centers, Adult, Aged, Aged, 80 and over, Area Under Curve, Bile Duct Neoplasms, Biliary Tract Surgical Procedures, Cholangiocarcinoma, Databases, Factual, Decision Support Techniques, Female, Gallbladder Neoplasms, Hepatectomy, Humans, Male, Middle Aged, Pancreaticoduodenectomy, Patient Readmission, Postoperative Complications, Predictive Value of Tests, ROC Curve, Reoperation, Retrospective Studies, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, United States, Young Adult
Show Abstract · Added April 10, 2018
BACKGROUND - The objective of this study is to evaluate use of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) online risk calculator for estimating common outcomes after operations for gallbladder cancer and extrahepatic cholangiocarcinoma.
METHODS - Subjects from the United States Extrahepatic Biliary Malignancy Consortium (USE-BMC) who underwent operation between January 1, 2000 and December 31, 2014 at 10 academic medical centers were included in this study. Calculator estimates of risk were compared to actual outcomes.
RESULTS - The majority of patients underwent partial or major hepatectomy, Whipple procedures or extrahepatic bile duct resection. For the entire cohort, c-statistics for surgical site infection (0.635), reoperation (0.680) and readmission (0.565) were less than 0.7. The c-statistic for death was 0.740. For all outcomes the actual proportion of patients experiencing an event was much higher than the median predicted risk of that event. Similarly, the group of patients who experienced an outcome did have higher median predicted risk than those who did not.
CONCLUSIONS - The ACS NSQIP risk calculator is easy to use but requires further modifications to more accurately estimate outcomes for some patient populations and operations for which validation studies show suboptimal performance.
Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
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Diagnostic value of histone 3 mutations in osteoclast-rich bone tumors.
Nohr E, Lee LH, Cates JM, Perizzolo M, Itani D
(2017) Hum Pathol 68: 119-127
MeSH Terms: Adolescent, Adult, Aged, Alberta, Biomarkers, Tumor, Bone Cysts, Aneurysmal, Bone Neoplasms, Child, Chondroblastoma, DNA Mutational Analysis, Diagnosis, Differential, Disease-Free Survival, Female, Genetic Predisposition to Disease, Giant Cell Tumor of Bone, Histones, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Mutation, Osteoclasts, Phenotype, Predictive Value of Tests, Tennessee, Time Factors, Young Adult
Show Abstract · Added November 1, 2018
Differentiating osteoclast-rich lesions of bone (giant cell tumor of bone [GCTB], chondroblastoma [CBA], and aneurysmal bone cyst [ABC]) can be challenging, especially in small biopsies or fine-needle aspirations. Mutations affecting codons 34 and 36 of either H3 Histone Family Member 3A (H3F3A) and/or 3B (H3F3B) are characteristically seen in GCTB and CBAs. We devised a simple assay to identify these mutations and evaluated its applicability for routine clinical diagnosis. One hundred twenty-four tissue specimens from 108 patients (43 GCTBs, 38 CBAs and 27 ABCs) were collected from the archives of the Calgary Laboratory Services/University of Calgary and Vanderbilt University Medical Center. Histology was reviewed by an expert orthopedic pathologist. A single base extension assay (SNaPshot) is used to interrogate each nucleotide in codons 34 and 36 of H3F3A and codon 36 of H3F3B. Final diagnoses were generated after re-reviewing cases and incorporating molecular findings. Of 43 GCTBs, 38 (88%) had an H3F3A G34W mutation; 35 of 38 CBAs (92%) had a K36M mutation in either H3F3B (N = 31; 82%) or H3F3A (N = 4; 11%); none of 27 ABCs had a tested mutation. Molecular findings changed the histomorphologic diagnosis in 5 cases (3 GCTB changed to ABC, and 2 ABC changed to GCTB). These findings support the diagnostic utility of mutational analysis for this differential diagnosis in certain challenging cases when clinicoradiologic and histomorphologic features are not definitive, particularly for distinguishing cellular ABC versus GCTB with secondary ABC.
Copyright © 2017 Elsevier Inc. All rights reserved.
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