Browsing by Subject "Risk assessment"
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Item Association of Body Mass Index With Colorectal Cancer Risk by Genome-Wide Variants(Oxford University Press, 2021) Campbell, Peter T.; Lin, Yi; Bien, Stephanie A.; Figueiredo, Jane C.; Harrison, Tabitha A.; Guinter, Mark A.; Berndt, Sonja I.; Brenner, Hermann; Chan, Andrew T.; Chang-Claude, Jenny; Gallinger, Steven J.; Gapstur, Susan M.; Giles, Graham G.; Giovannucci, Edward; Gruber, Stephen B.; Gunter, Marc; Hoffmeister, Michael; Jacobs, Eric J.; Jenkins, Mark A.; Marchand, Loic Le; Li, Li; McLaughlin, John R.; Murphy, Neil; Milne, Roger L.; Newcomb, Polly A.; Newton, Christina; Ogino, Shuji; Potter, John D.; Rennert, Gad; Rennert, Hedy S.; Robinson, Jennifer; Sakoda, Lori C.; Slattery, Martha L.; Song, Yiqing; White, Emily; Woods, Michael O.; Casey, Graham; Hsu, Li; Peters, Ulrike; Epidemiology, School of Public HealthBackground: Body mass index (BMI) is a complex phenotype that may interact with genetic variants to influence colorectal cancer risk. Methods: We tested multiplicative statistical interactions between BMI (per 5 kg/m2) and approximately 2.7 million single nucleotide polymorphisms with colorectal cancer risk among 14 059 colorectal cancer case (53.2% women) and 14 416 control (53.8% women) participants. All analyses were stratified by sex a priori. Statistical methods included 2-step (ie, Cocktail method) and single-step (ie, case-control logistic regression and a joint 2-degree of freedom test) procedures. All statistical tests were two-sided. Results: Each 5 kg/m2 increase in BMI was associated with higher risks of colorectal cancer, less so for women (odds ratio [OR] = 1.14, 95% confidence intervals [CI] = 1.11 to 1.18; P = 9.75 × 10-17) than for men (OR = 1.26, 95% CI = 1.20 to 1.32; P = 2.13 × 10-24). The 2-step Cocktail method identified an interaction for women, but not men, between BMI and a SMAD7 intronic variant at 18q21.1 (rs4939827; Pobserved = .0009; Pthreshold = .005). A joint 2-degree of freedom test was consistent with this finding for women (joint P = 2.43 × 10-10). Each 5 kg/m2 increase in BMI was more strongly associated with colorectal cancer risk for women with the rs4939827-CC genotype (OR = 1.24, 95% CI = 1.16 to 1.32; P = 2.60 × 10-10) than for women with the CT (OR = 1.14, 95% CI = 1.09 to 1.19; P = 1.04 × 10-8) or TT (OR = 1.07, 95% CI = 1.01 to 1.14; P = .02) genotypes. Conclusion: These results provide novel insights on a potential mechanism through which a SMAD7 variant, previously identified as a susceptibility locus for colorectal cancer, and BMI may influence colorectal cancer risk for women.Item Caries risk assessment using different Cariogram models. A comparative study about concordance in different populations—Adults and children(Public Library of Science, 2022-06-24) Cagetti, Maria Grazia; Bontà, Giuliana; Lara, Juan Sebastian; Campus, Guglielmo; Cariology, Operative Dentistry and Dental Public Health, School of DentistryThis methodological survey aimed to verify whether there is concordance among several Cariogram different risk models at different thresholds, comparing both children and adult populations and how each risk/protective factor weight on the overall caries risk profile. Three groups' data (two in children and one in adults) were obtained from previous studies, while a fourth, in young adults, was ad hoc enrolled. Different caries risk levels were assessed: a) three risk categories with two different thresholds as: "low risk" = 61-100% or 81-100% chance to avoid caries, "moderate risk" = 41-60% or 21-80% and "high risk" = 0-40% or 0-20%, named model 1 and 2; b) four risk categories with two different thresholds as: "low risk" = 61-100% or 76-100%, "moderate/low risk" = 41-60% or 51-75%; "moderate/high risk" = 21-40% or 26-50% and "high risk" = 0-20% or 0-25%, model 3 and 4; c) five risk categories as: "very low risk" = 81-100%; "low risk" = 61-80% "moderate risk" = 41-60%; "high risk" = 21-40% and "very high risk" = 0-20%, model 5. Concordance of the different Cariogram risk categories among the four groups was calculated using Cohen's kappa. The weight of the association between all Cariogram models toward the Cariogram risk variables was evaluated by ordinal logistic regression models. Considering Cariogram model 1 and 2, Cohen's Kappa values ranged from 0.40 (SE = 0.07) for the young adult group to 0.71 (SE = 0.05) for the adult one. Cohen's Kappa values ranged from 0.14 (SE = 0.03 p<0.01) for the adult group to 0.62 (SE = 0.02) for the two groups of children in models 3 and 4. Statistically significant associations were found for all Cariogram risk variables excepting Fluoride program in models 4 and 5 and the overall risk on children's samples. Caries experience showed a quite variable weight in the different models in both adult groups. In the regression analyses, adult groups' convergence was not always achievable since variations in associations between caries risk and different risk variables were narrower compared to other samples. Significant differences in caries risk stratification using different thresholds stands out from data analysis; consequently, risk assessments need to be carefully considered due to the risk of misleadingly choosing preventive and research actions.Item Characterization of Behavioral Profiles for Inbred P and NP and Congenic P.NP and NP.P Rats(2012-08-27) Jensen, Meredith; Grahame, Nicholas J.; Stewart, Robert; Czachowski, Cristine; Roman, ErikaAlcoholism inheritance rates have been estimated as high as 60% in a human population. Many significant features of alcohol dependence have been replicated in rodent animal models of alcoholism, however not in totality. These animal models include inbred preferring (iP) and nonpreferring (iNP) rat types. Congenic rats have been engineered from the iP and iNP strains whereby a P congenic rat has in its genome a well-chosen chromosomal portion taken from an NP rat (P.NP) and, reciprocally, an NP congenic rat has acquired the analogous DNA from a P rat (NP.P). In this case, a quantitative trait locus (QTL) from chromosome 4 is the donor genetic material for the congenic rats. It is of great interest to further study this chromosome 4 QTL because it has been found to control a significant portion of ethanol consumption behavior in iP and iNP rats. This study aimed to behaviorally profile the iP, iNP and reciprocal congenic rats. As a result of the behavioral profiling of these genetically related groups, some conclusions could be made regarding which behaviors appear to be controlled by the chromosome 4 donor DNA.This study primarily utilized the Multivariate Concentric Square Field apparatus (MCSF) to characterize behavioral profiles for the inbred and congenic rats. The Open field (OF) and Elevated plus maze (EPM) supported this effort. The MCSF is valuable in that it allows for the animals to interact within an environment that has ethological value. The 12 different zones that make up the field are characterized by some functional quality in terms of type and duration of behavior performed, etc. The behavioral data is aggregated and finally represented in terms of five functional categories, the elements of the behavioral profile: general activity, exploratory activity, risk assessment, risk taking, and shelter seeking. The study hypotheses were shaped by prior research suggesting that iPs should display lower general activity and risk taking strategy than iNPs in the MCSF. Inbred Ps should be more active in the OF and spend more time in the center of the EPM. Generally, it is expected that the iP QTL confer behavioral phenotypes to the iNP strain that deviate toward a "P" behavioral phenotype and reciprocally, the iNP QTL confer behavioral phenotypes to the iP strain that deviate toward an "NP" behavioral phenotype. The results showed that iP rats performed more risk assessment and risk taking behavior and less shelter seeking and anxiety-like behavior than iNP rats. It followed that P.NP congenic rats significantly downgraded their risk assessment and risk taking behavior when compared to iP rats. This decrease can be attributed to the chromosome 4 QTL donated from the iNP breed. All together this study concludes that risk assessment and risk taking behavior in the iP rats is controlled by the same DNA region that, in part, determines voluntary intake of ethanol consumption. Further fine mapping of the QTL region should help in discovering if the same DNA sequences that influence ethanol intake also significantly influence risk behavior.Item Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements(Wiley, 2017-04) Bonkovsky, Herbert L.; Kleiner, David E.; Gu, Jiezhun; Odin, Joseph A.; Russo, Mark W.; Navarro, Victor M.; Fontana, Robert J.; Ghabril, Marwan S.; Barnhart, Huiman; Hoofnagle, Jay H.; U.S. Drug Induced Liver Injury Network Investigators; Medicine, School of MedicineBile duct loss during the course of drug-induced liver injury is uncommon, but can be an indication of vanishing bile duct syndrome (VBDS). In this work, we assess the frequency, causes, clinical features, and outcomes of cases of drug-induced liver injury with histologically proven bile duct loss. All cases of drug-induced liver injury enrolled into a prospective database over a 10-year period that had undergone liver biopsies (n = 363) were scored for the presence of bile duct loss and assessed for clinical and laboratory features, causes, and outcomes. Twenty-six of the 363 patients (7%) with drug-, herbal-, or dietary-supplement-associated liver injury had bile duct loss on liver biopsy, which was moderate to severe (<50% of portal areas with bile ducts) in 14 and mild (50%-75%) in 12. The presenting clinical features of the 26 cases varied, but the most common clinical pattern was a severe cholestatic hepatitis. The implicated agents included amoxicillin/clavulanate (n = 3), temozolomide (n = 3), various herbal products (n = 3), azithromycin (n = 2), and 15 other medications or dietary supplements. Compared to those without, those with bile duct loss were more likely to develop chronic liver injury (94% vs. 47%), which was usually cholestatic and sometimes severe. Five patients died and 2 others underwent liver transplantation for progressive cholestasis despite treatment with corticosteroids and ursodiol. The most predictive factor of poor outcome was the degree of bile duct loss on liver biopsy. CONCLUSION: Bile duct loss during acute cholestatic hepatitis is an ominous early indicator of possible VBDS, for which at present there are no known means of prevention or therapy.Item The Creation and Validation of the Activation-Valence Affective Traits Survey (AVATS)(2012-07-03) Coskunpinar, Ayca; Cyders, Melissa A.; Devine, Dennis J. (Dennis John); Stewart, Jesse C.Aim: The goals of the current studies were to (a) create a measure of affective traits that can assess both the discrete and the underlying dimensions of affective traits and (b) examine the reliability and validity of the scale in two independent samples. Participants: Participants were undergraduate students at a large, public US mid-western university (Study 1 N = 616; Study 2 N = 510). The mean age for Study 1 was 21.10 (SD = 5.05) and 21.02 for Study 2 (SD = 4.96). Design: Exploratory and confirmatory factor analyses were conducted to examine internal factor structure of the scale. A series of correlational, reliability, and hierarchical regression analyses were conducted to examine convergent, divergent, and criterion-related validity of the new scale. Findings: Activation-Valence Affective Traits Survey (AVATS) had good reliability and adequate construct, convergent, and discriminant validity as a measure of affective traits. Conclusions: This study introduces a new scale for measuring affective traits that offers more information on both the categorical and dimensional conceptualizations of affective traits, which also has predictive utility in relation to problem-related alcohol consumption.Item Higher blood selenium level is associated with lower risk of hyperhomocysteinemia in the elderly(Elsevier, 2023-01) Wang, Ting; Su, Liqin; Chen, Xi; Wang, Sisi; Han, Xu; Cheng, Yibin; Lin, Shaobin; Ding, Liang; Liu, Jingyi; Chen, Chen; Unverzagt, Frederick W.; Hake, Ann M.; Jin, Yinlong; Gao, Sujuan; Biostatistics and Health Data Science, School of MedicineBackground and aims Earlier studies have reported inconsistent association between selenium (Se) and homocysteine (Hcy) levels, while no evidence could be found from Chinese population. To fill this gap, we investigated the association between blood Se and hyperhomocysteinemia (HHcy) of rural elderly population in China. Methods A cross-sectional study on 1823 participants aged 65 and older from four Chinese rural counties was carried out in this study. Whole blood Se and serum Hcy concentrations were measured in fasting blood samples. Analysis of covariance and restricted cubic spline models were used to examine the association between Se and Hcy levels. Logistic regression models were used to evaluate the risk of prevalent HHcy among four Se quartile groups after adjusting for covariates. Results For this sample, the mean blood Se concentration was 156.34 (74.65) μg/L and the mean serum Hcy concentration was 17.25 (8.42) μmol/L. A significant non-linear relationship was found between blood Se and serum Hcy, the association was inverse when blood Se was less than 97.404 μg/L and greater than 156.919 μg/L. Participants in the top three blood Se quartile groups had significantly lower risk of prevalent HHcy compared with the lowest quartile group. When defined as Hcy> 10 μmol/L, the odds ratios and 95% confidence interval of HHcy were 0.600 (0.390, 0.924), 0.616 (0.398, 0.951) and 0.479 (0.314, 0.732) for Q2, Q3, and Q4 Se quartile groups compared with the Q1 group, respectively. When defined as Hcy≥ 15 μmol/L, the odds ratios and 95% confidence interval of HHcy were 0.833 (0.633, 1.098) and 0.827 (0.626, 1.092), 0.647 (0.489, 0.857) for Q2, Q3, and Q4 Se quartile groups compared with Q1 group. Conclusions Our findings suggest that higher blood Se level could be a protective factor for HHcy in the elderlyItem Hyponatremia and fractures: should hyponatremia be further studied as a potential biochemical risk factor to be included in FRAX algorithms?(Springer, 2017) Ayus, J. C.; Bellido, T.; Negri, A. L.; Anatomy, Cell Biology and Physiology, School of MedicineThe Fracture Risk Assessment Tool (FRAX®) was developed by the WHO Collaborating Centre for metabolic bone diseases to evaluate fracture risk of patients. It is based on patient models that integrate the risk associated with clinical variables and bone mineral density (BMD) at the femoral neck. The clinical risk factors included in FRAX were chosen to include only well-established and independent variables related to skeletal fracture risk. The FRAX tool has acquired worldwide acceptance despite having several limitations. FRAX models have not included biochemical derangements in estimation of fracture risk due to the lack of validation in large prospective studies. Recently, there has been an increasing number of studies showing a relationship between hyponatremia and the occurrence of fractures. Hyponatremia is the most frequent electrolyte abnormality measured in the clinic, and serum sodium concentration is a very reproducible, affordable, and readily obtainable measurement. Thus, we think that hyponatremia should be further studied as a biochemical risk factor for skeletal fractures prediction, particularly those at the hip which carries the greatest morbidity and mortality. To achieve this will require the collection of large patient cohorts from diverse geographical locations that include a measure of serum sodium in addition to the other FRAX variables in large numbers, in both sexes, over a wide age range and with wide geographical representation. It would also require the inclusion of data on duration and severity of hyponatremia. Information will be required both on the risk of fracture associated with the occurrence and length of exposure to hyponatremia and to the relationship with the other risk variables included in FRAX and also the independent effect on the occurrence of death which is increased by hyponatremia.Item Inconsistent Associations Between Risk Factor Profiles and Adjuvant Radiation Therapy (ART) Treatment in Patients with Cutaneous Squamous Cell Carcinoma and Utility of the 40-Gene Expression Profile to Refine ART Guidance(Springer, 2024) Moody, Brent R.; Farberg, Aaron S.; Somani, Ally-Khan; Taylor, Walton A.; Dermatology, School of MedicineIntroduction: National Comprehensive Cancer Network (NCCN) recommendations for adjuvant radiation therapy (ART) use are similar for High Risk and Very High Risk cutaneous squamous cell carcinoma (cSCC) with negative post-surgical margins. Although studies report reductions in disease progression following ART treatment, ART use is likely inconsistent when guided by available risk factors. This study evaluated the association of ART with clinical risk factors in ART-treated and untreated patients and showed the clinical utility of the 40-gene expression profile (40-GEP) for guiding ART. Methods: A multicenter study of 954 patients was conducted with institutional review board (IRB) approval. The 40-GEP test was performed using primary tumor tissue from patients with either a minimum of 3 years of follow-up or a documented regional or distant metastasis. Unsupervised hierarchical cluster analysis identified patterns of clinical risk factors for ART-treated patients, then identified untreated patients with matching risk factor profiles. Results were cross-referenced to 40-GEP test results to determine utility of the test to guide ART. Results: Analysis demonstrated inconsistent implementation of ART for eligible patients. Cluster analysis identified four patient profiles based on clusters of risk factors and, notably, matching profiles in ART-treated and untreated patients. Further, the analysis identified patients who received but could have deferred ART on the basis of 40-GEP test result and biologically low risk of metastasis, and untreated patients who likely would have benefitted from ART on the basis of their 40-GEP test result. Conclusions: ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART.Item Integrating the 40-Gene Expression Profile (40-GEP) Test Improves Metastatic Risk-Stratification Within Clinically Relevant Subgroups of High-Risk Cutaneous Squamous Cell Carcinoma (cSCC) Patients(Springer, 2024) Wysong, Ashley; Somani, Ally-Khan; Ibrahim, Sherrif F.; Cañueto, Javier; Fitzgerald, Alison L.; Siegel, Jennifer J.; Prasai, Anesh; Goldberg, Matthew S.; Farberg, Aaron S.; Regula, Christie; Bar, Anna; Kasprzak, Julia; Brodland, David G.; Koyfman, Shlomo A.; Arron, Sarah T.; Dermatology, School of MedicineIntroduction: The validated 40-gene expression profile (40-GEP) test independently stratifies risk of regional or distant metastasis for cutaneous squamous cell carcinoma (cSCC) tumors with high-risk clinicopathologic features. This study evaluated the stratification of risk by the 40-GEP test in a large cohort of tumors with one or more high-risk factors and in clinically relevant subgroups, including tumors within National Comprehensive Cancer Network (NCCN) high- and very-high-risk groups, lower-stage BWH T1 and T2a tumors, and patients > 65 years old. Methods: This multicenter (n = 58) performance study of the 40-GEP included 897 patients. Kaplan-Meier analyses were performed to assess risk stratification profiles for 40-GEP Class 1 (low), Class 2A (higher) and Class 2B (highest) risk groups, while nested Cox regression models were used to compare risk prediction of clinicopathologic risk classification systems versus risk classification systems in combination with 40-GEP. Results: Patients classified as 40-GEP Class 1, Class 2A, or Class 2B had significantly different metastatic risk profiles (p < 0.0001). Integrating 40-GEP results into models with individual clinicopathologic risk factors or risk classification systems (Brigham and Women's Hospital, American Joint Committee on Cancer Staging Manual, 8th Edition) and NCCN demonstrated significant improvement in accuracy for prediction of metastatic events (ANOVA for model deviance, p < 0.0001 for all models). Conclusion: The 40-GEP test demonstrates accurate, independent, clinically actionable stratification of metastatic risk and improves predictive accuracy when integrated into risk classification systems. The improved accuracy of risk assessment when including tumor biology via the 40-GEP test ensures more risk-aligned, personalized patient management decisions.Item Opioid-related risk perceptions in chronic pain: influence of patient gender and previous misuse behaviors(International Association for the Study of Pain, 2021-07) Grant, Alexis D.; Miller, Megan M.; Anastas, Tracy M.; Quinn, Patrick; Lok, Benjamin; Hirsh, Adam T.; Psychology, School of ScienceLittle is known about the factors that influence providers' perceptions of patient risk for aberrant opioid use. Patient gender may interact with previous opioid misuse to influence these perceptions. We asked 131 physicians to view videos and vignettes for 8 virtual patients with chronic pain. Gender (male/female) and previous prescription opioid misuse (present/absent) varied across patients; the vignettes were otherwise balanced on demographic and clinical characteristics. For each patient, providers assessed 4 risk domains: opioid-related adverse events, opioid misuse or abuse, opioid addiction, and opioid diversion. Results indicated a significant gender-by-misuse interaction for risk of opioid misuse orabuse. When previous misuse behaviors were absent, providers rated men at higher risk; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid-related adverse events. Providers perceived men to be at higher risk when previous misuse behaviors were absent; there was no gender difference when previous misuse behaviors were present. A significant gender-by-misuse interaction was found for risk of opioid addiction. Providers rated women at higher risk when previous misuse behaviors were present and men at higher risk when previous misuse behaviors were absent. There were significant main effects of gender and misuse for risk of opioid diversion. Providers rated men and those with previous misuse behaviors at higher risk. These results demonstrate that patient gender and previous opioid misuse have unique and interactive effects on provider perceptions of prescription opioid–related risks. Studies are needed to identify the mechanisms underlying these effects, such as gender-based stereotypes about risk-taking and drug abuse.