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Item A Scoring System for Predicting Nonunion After Intramedullary Nailing of Femoral Shaft Fractures(Wolters Kluwer, 2024-09-04) Kraus, Kent R.; Flores, Joshua W.; Slaven, James E.; Sharma, Ishani; Arnold, Payton K.; Mullis, Brian H.; Natoli, Roman M.; Orthopaedic Surgery, School of MedicineIntroduction: Femoral shaft nonunion negatively affects patient quality of life. Although multiple risk factors have been identified for femoral shaft nonunion after intramedullary nail (IMN) fixation, there is no quantitative model for predicting nonunion. Study description: The study is a retrospective cohort study of patients with femoral shaft fractures treated at two level one trauma centers who were followed to fracture union or nonunion. Patient, injury, and surgical characteristics were analyzed to create a quantitative model for nonunion risk after intramedullary nailing. Methods: Eight hundred one patients aged 18 years and older with femoral shaft fractures treated with reamed, locked IMNs were identified. Risk factors including demographics, comorbidities, surgical variables, and injury-related characteristics were evaluated. Multivariate analysis was conducted, and several variables were included in a scoring system to predict nonunion risk. Results: The overall nonunion rate was 7.62% (61/801). Multivariate analysis showed significant association among pulmonary injury (odds ratio [OR] = 2.19, P = 0.022), open fracture (OR=2.36, P = 0.02), current smoking (OR=3.05, P < 0.001), postoperative infection (OR=12.1, P = 0.007), AO/OTA fracture pattern type A or B (OR=0.43, P = 0.014), and percent cortical contact obtained intraoperatively ≥25% (OR=0.41, P = 0.021) and nonunion. The scoring system created to quantitatively stratify nonunion risk showed that a score of 3 or more yielded an OR of 6.38 for nonunion (c-statistic = 0.693, P < 0.0001). Conclusions: Femoral shaft nonunion risk is quantifiable based on several independent injury, patient, and surgical factors. This scoring system is an additional tool for clinical decision making when caring for patients with femoral shaft fractures treated with IMNs.Item Acceptance of Automated Social Risk Scoring in the Emergency Department: Clinician, Staff, and Patient Perspectives(University of California, 2024) Mazurenko, Olena; Hirsh, Adam T.; Harle, Christopher A.; McNamee, Cassidy; Vest, Joshua R.; Health Policy and Management, Richard M. Fairbanks School of Public HealthIntroduction: Healthcare organizations are under increasing pressure from policymakers, payers, and advocates to screen for and address patients' health-related social needs (HRSN). The emergency department (ED) presents several challenges to HRSN screening, and patients are frequently not screened for HRSNs. Predictive modeling using machine learning and artificial intelligence, approaches may address some pragmatic HRSN screening challenges in the ED. Because predictive modeling represents a substantial change from current approaches, in this study we explored the acceptability of HRSN predictive modeling in the ED. Methods: Emergency clinicians, ED staff, and patient perspectives on the acceptability and usage of predictive modeling for HRSNs in the ED were obtained through in-depth semi-structured interviews (eight per group, total 24). All participants practiced at or had received care from an urban, Midwest, safety-net hospital system. We analyzed interview transcripts using a modified thematic analysis approach with consensus coding. Results: Emergency clinicians, ED staff, and patients agreed that HRSN predictive modeling must lead to actionable responses and positive patient outcomes. Opinions about using predictive modeling results to initiate automatic referrals to HRSN services were mixed. Emergency clinicians and staff wanted transparency on data inputs and usage, demanded high performance, and expressed concern for unforeseen consequences. While accepting, patients were concerned that prediction models can miss individuals who required services and might perpetuate biases. Conclusion: Emergency clinicians, ED staff, and patients expressed mostly positive views about using predictive modeling for HRSNs. Yet, clinicians, staff, and patients listed several contingent factors impacting the acceptance and implementation of HRSN prediction models in the ED.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; Comprehensive Care and Allied Professions, 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 Commentary: Novel strategies and new tools to curtail the health effects of pesticides(Springer Nature, 2021-08-03) Benbrook, Charles; Perry, Melissa J.; Belpoggi, Fiorella; Landrigan, Philip J.; Perro, Michelle; Mandrioli, Daniele; Antoniou, Michael N.; Winchester, Paul; Mesnage, Robin; Pediatrics, School of MedicineBackground: Flaws in the science supporting pesticide risk assessment and regulation stand in the way of progress in mitigating the human health impacts of pesticides. Critical problems include the scope of regulatory testing protocols, the near-total focus on pure active ingredients rather than formulated products, lack of publicly accessible information on co-formulants, excessive reliance on industry-supported studies coupled with reticence to incorporate published results in the risk assessment process, and failure to take advantage of new scientific opportunities and advances, e.g. biomonitoring and "omics" technologies. Recommended actions: Problems in pesticide risk assessment are identified and linked to study design, data, and methodological shortcomings. Steps and strategies are presented that have potential to deepen scientific knowledge of pesticide toxicity, exposures, and risks. We propose four solutions: (1) End near-sole reliance in regulatory decision-making on industry-supported studies by supporting and relying more heavily on independent science, especially for core toxicology studies. The cost of conducting core toxicology studies at labs not affiliated with or funded directly by pesticide registrants should be covered via fees paid by manufacturers to public agencies. (2) Regulators should place more weight on mechanistic data and low-dose studies within the range of contemporary exposures. (3) Regulators, public health agencies, and funders should increase the share of exposure-assessment resources that produce direct measures of concentrations in bodily fluids and tissues. Human biomonitoring is vital in order to quickly identify rising exposures among vulnerable populations including applicators, pregnant women, and children. (4) Scientific tools across disciplines can accelerate progress in risk assessments if integrated more effectively. New genetic and metabolomic markers of adverse health impacts and heritable epigenetic impacts are emerging and should be included more routinely in risk assessment to effectively prevent disease. Conclusions: Preventing adverse public health outcomes triggered or made worse by exposure to pesticides will require changes in policy and risk assessment procedures, more science free of industry influence, and innovative strategies that blend traditional methods with new tools and mechanistic insights.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.
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