Browsing by Subject "Risk Assessment"
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Item Open Access A clinician's guide to the ABCs of cardiovascular disease prevention: the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and American College of Cardiology Cardiosource Approach to the Million Hearts Initiative.(Clinical cardiology, 2013-07) Hsu, Steven; Ton, Van-Khue; Dominique Ashen, M; Martin, Seth S; Gluckman, Ty J; Kohli, Payal; Sisson, Stephen D; Blumenthal, Roger S; Blaha, Michael JAtherosclerotic cardiovascular disease (CVD) is the leading cause of death in the United States and worldwide. Fortunately, it is often preventable with early adoption of lifestyle modification, prevention of risk factor onset, and aggressive treatment of existing risk factors. The Million Hearts Initiative is an effort by the Centers for Disease Control that aims to prevent 1 million myocardial infarctions and strokes over the next 5 years. As part of this initiative, we present a simply organized "ABCDE" approach for guiding a consistent comprehensive approach to managing cardiovascular risk in daily clinical practice. ABCDE stands for assessment of risk, antiplatelet therapy, blood pressure management, cholesterol management, cigarette/tobacco cessation, diet and weight management, diabetes prevention and treatment, and exercise, interventions regularly used to reduce cardiovascular (CV) risk. Throughout this article we summarize recommendations related to each topic and reference landmark trials and data that support our approach. We believe that the ABCDE approach will be the core framework for addressing CV risk in our effort to prevent CVD.Item Open Access A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome.(Haematologica, 2017-06) Shekhovtsova, Zhanna; Bonfim, Carmem; Ruggeri, Annalisa; Nichele, Samantha; Page, Kristin; AlSeraihy, Amal; Barriga, Francisco; de Toledo Codina, José Sánchez; Veys, Paul; Boelens, Jaap Jan; Mellgren, Karin; Bittencourt, Henrique; O'Brien, Tracey; Shaw, Peter J; Chybicka, Alicja; Volt, Fernanda; Giannotti, Federica; Gluckman, Eliane; Kurtzberg, Joanne; Gennery, Andrew R; Rocha, Vanderson; Eurocord, Cord Blood Committee of Cellular Therapy and Immunobiology Working Party of the EBMT, Federal University of Parana, Duke University Medical Center and Inborn Errors Working Party of the EBMTWiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II-IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4-5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor.Item Open Access A risk score for in-hospital death in patients admitted with ischemic or hemorrhagic stroke.(J Am Heart Assoc, 2013-01-28) Smith, Eric E; Shobha, Nandavar; Dai, David; Olson, DaiWai M; Reeves, Mathew J; Saver, Jeffrey L; Hernandez, Adrian F; Peterson, Eric D; Fonarow, Gregg C; Schwamm, Lee HBACKGROUND: We aimed to derive and validate a single risk score for predicting death from ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH). METHODS AND RESULTS: Data from 333 865 stroke patients (IS, 82.4%; ICH, 11.2%; SAH, 2.6%; uncertain type, 3.8%) in the Get With The Guidelines-Stroke database were used. In-hospital mortality varied greatly according to stroke type (IS, 5.5%; ICH, 27.2%; SAH, 25.1%; unknown type, 6.0%; P<0.001). The patients were randomly divided into derivation (60%) and validation (40%) samples. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model in the overall population and in the subset with the National Institutes of Health Stroke Scale (NIHSS) recorded (37.1%). The c statistic, a measure of how well the models discriminate the risk of death, was 0.78 in the overall validation sample and 0.86 in the model including NIHSS. The model with NIHSS performed nearly as well in each stroke type as in the overall model including all types (c statistics for IS alone, 0.85; for ICH alone, 0.83; for SAH alone, 0.83; uncertain type alone, 0.86). The calibration of the model was excellent, as demonstrated by plots of observed versus predicted mortality. CONCLUSIONS: A single prediction score for all stroke types can be used to predict risk of in-hospital death following stroke admission. Incorporation of NIHSS information substantially improves this predictive accuracy.Item Open Access Accelerated epigenetic age as a biomarker of cardiovascular sensitivity to traffic-related air pollution.(Aging, 2020-12) Ward-Caviness, Cavin K; Russell, Armistead G; Weaver, Anne M; Slawsky, Erik; Dhingra, Radhika; Kwee, Lydia Coulter; Jiang, Rong; Neas, Lucas M; Diaz-Sanchez, David; Devlin, Robert B; Cascio, Wayne E; Olden, Kenneth; Hauser, Elizabeth R; Shah, Svati H; Kraus, William EBackground
Accelerated epigenetic age has been proposed as a biomarker of increased aging, which may indicate disruptions in cellular and organ system homeostasis and thus contribute to sensitivity to environmental exposures.Methods
Using 497 participants from the CATHGEN cohort, we evaluated whether accelerated epigenetic aging increases cardiovascular sensitivity to traffic-related air pollution (TRAP) exposure. We used residential proximity to major roadways and source apportioned air pollution models as measures of TRAP exposure, and chose peripheral arterial disease (PAD) and blood pressure as outcomes based on previous associations with TRAP. We used Horvath epigenetic age acceleration (AAD) and phenotypic age acceleration (PhenoAAD) as measures of age acceleration, and adjusted all models for chronological age, race, sex, smoking, and socioeconomic status.Results
We observed significant interactions between TRAP and both AAD and PhenoAAD. Interactions indicated that increased epigenetic age acceleration elevated associations between proximity to roadways and PAD. Interactions were also observed between AAD and gasoline and diesel source apportioned PM2.5.Conclusion
Epigenetic age acceleration may be a biomarker of sensitivity to air pollution, particularly for TRAP in urban cohorts. This presents a novel means by which to understand sensitivity to air pollution and provides a molecular measure of environmental sensitivity.Item Open Access Addressing barriers to optimal oral anticoagulation use and persistence among patients with atrial fibrillation: Proceedings, Washington, DC, December 3-4, 2012.(American heart journal, 2014-09) Hess, Paul L; Mirro, Michael J; Diener, Hans-Christoph; Eikelboom, John W; Al-Khatib, Sana M; Hylek, Elaine M; Bosworth, Hayden B; Gersh, Bernard J; Singer, Daniel E; Flaker, Greg; Mega, Jessica L; Peterson, Eric D; Rumsfeld, John S; Steinberg, Benjamin A; Kakkar, Ajay K; Califf, Robert M; Granger, Christopher B; Atrial Fibrillation Think-Tank ParticipantsApproximately half of patients with atrial fibrillation and with risk factors for stroke are not treated with oral anticoagulation (OAC), whether it be with vitamin K antagonists (VKAs) or novel OACs (NOACs); and of those treated, many discontinue treatment. Leaders from academia, government, industry, and professional societies convened in Washington, DC, on December 3-4, 2012, to identify barriers to optimal OAC use and adherence and to generate potential solutions. Participants identified a broad range of barriers, including knowledge gaps about stroke risk and the relative risks and benefits of anticoagulant therapies; lack of awareness regarding the potential use of NOAC agents for VKA-unsuitable patients; lack of recognition of expanded eligibility for OAC; lack of availability of reversal agents and the difficulty of anticoagulant effect monitoring for the NOACs; concerns with the bleeding risk of anticoagulant therapy, especially with the NOACs and particularly in the setting of dual antiplatelet therapy; suboptimal time in therapeutic range for VKA; and costs and insurance coverage. Proposed solutions were to define reasons for oral anticoagulant underuse classified in ways that can guide intervention and improve use, to increase awareness of stroke risk as well as the benefits and risks of OAC use via educational initiatives and feedback mechanisms, to better define the role of VKA in the current therapeutic era including eligibility and ineligibility for different anticoagulant therapies, to identify NOAC reversal agents and monitoring strategies and make knowledge regarding their use publicly available, to minimize the duration of dual antiplatelet therapy and concomitant OAC where possible, to improve time in therapeutic range for VKA, to leverage observational data sets to refine understanding of OAC use and outcomes in general practice, and to better align health system incentives.Item Open Access Alcohol limits in older people.(Addiction (Abingdon, England), 2012-09) Crome, Ilana; Li, Ting-Kai; Rao, Rahul; Wu, Li-TzyItem Open Access An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disruptors on homeostasis in adults.(Environmental health perspectives, 1999-08) Ben-Jonathan, N; Cooper, RL; Foster, P; Hughes, CL; Hoyer, PB; Klotz, D; Kohn, M; Lamb, DJ; Stancel, GMThe workshop "Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels" was held to provide a forum for discussions and recommendations of methods and data needed to improve risk assessments of endocrine disruptors. This article was produced by a working group charged with determining the basic mechanistic information that should be considered when designing models to quantitatively assess potential risks of environmental endocrine disruptors in adults. To reach this goal, we initially identified a set of potential organ system toxicities in males and females on the basis of known and/or suspected effects of endocrine disruptors on estrogen, androgen, and thyroid hormone systems. We used this integrated, systems-level approach because endocrine disruptors have the potential to exert toxicities at many levels and by many molecular mechanisms. Because a detailed analysis of all these untoward effects was beyond the scope of this workshop, we selected the specific end point of testicular function for a more detailed analysis. The goal was to identify the information required to develop a quantitative model(s) of the effects of endocrine disruptors on this system while focusing on spermatogenesis, sperm characteristics, and testicular steroidogenesis as specific markers. Testicular function was selected because it is a prototypical integrated end point that can be affected adversely by individual endocrine disruptors or chemical mixtures acting at one specific site or at multiple sites. Our specific objective was to gather the information needed to develop models in the adult organism containing functional homeostatic mechanisms, and for this reason we did not consider possible developmental toxicities. Homeostatic mechanisms have the potential to ameliorate or lessen the effects of endocrine disruptors, but these pathways are also potential target sites for the actions of these chemicals.Item Open Access An extensive new literature concerning low-dose effects of bisphenol A shows the need for a new risk assessment.(Environmental health perspectives, 2005-08) vom Saal, Frederick S; Hughes, ClaudeBisphenol A (BPA) is the monomer used to manufacture polycarbonate plastic, the resin lining of cans, and other products, with global capacity in excess of 6.4 billion lb/year. Because the ester bonds in these BPA-based polymers are subject to hydrolysis, leaching of BPA has led to widespread human exposure. A recent report prepared by the Harvard Center for Risk Analysis and funded by the American Plastics Council concluded that evidence for low-dose effects of BPA is weak on the basis of a review of only 19 studies; the report was issued after a delay of 2.5 years. A current comprehensive review of the literature reveals that the opposite is true. As of December 2004, there were 115 published in vivo studies concerning low-dose effects of BPA, and 94 of these report significant effects. In 31 publications with vertebrate and invertebrate animals, significant effects occurred below the predicted "safe" or reference dose of 50 microg/kg/day BPA. An estrogenic mode of action of BPA is confirmed by in vitro experiments, which describe disruption of cell function at 10(-12) M or 0.23 ppt. Nonetheless, chemical manufacturers continue to discount these published findings because no industry-funded studies have reported significant effects of low doses of BPA, although > 90% of government-funded studies have reported significant effects. Some industry-funded studies have ignored the results of positive controls, and many studies reporting no significant effects used a strain of rat that is inappropriate for the study of estrogenic responses. We propose that a new risk assessment for BPA is needed based on a) the extensive new literature reporting adverse effects in animals at doses below the current reference dose; b) the high rate of leaching of BPA from food and beverage containers, leading to widespread human exposure; c) reports that the median BPA level in human blood and tissues, including in human fetal blood, is higher than the level that causes adverse effects in mice; and d) recent epidemiologic evidence that BPA is related to disease in women.Item Open Access Appropriate Risk Stratification and Accounting for Age-Adjusted Reciprocal Changes in the Thoracolumbar Spine Reduces the Incidence and Magnitude of Distal Junctional Kyphosis in Cervical Deformity Surgery.(Spine, 2021-11) Passias, Peter G; Bortz, Cole; Pierce, Katherine E; Kummer, Nicholas A; Lafage, Renaud; Diebo, Bassel G; Line, Breton G; Lafage, Virginie; Burton, Douglas C; Klineberg, Eric O; Kim, Han Jo; Daniels, Alan H; Mundis, Gregory M; Protopsaltis, Themistocles S; Eastlack, Robert K; Sciubba, Daniel M; Bess, Shay; Schwab, Frank J; Shaffrey, Christopher I; Smith, Justin S; Ames, Christopher P; International Spine Study Group (ISSG)Study design
Retrospective cohort study of a prospective cervical deformity (CD) database.Objective
Identify factors associated with distal junctional kyphosis (DJK); assess differences across DJK types.Summary of background data
DJK may develop as compensation for mal-correction of sagittal deformity in the thoracic curve. There is limited understanding of DJK drivers, especially for different DJK types.Methods
Included: patients with pre- and postoperative clinical/radiographic data. Excluded: patients with previous fusion to L5 or below. DJK was defined per surgeon note or DJK angle (kyphosis from LIV to LIV-2)<-10°, and pre- to postoperative change in DJK angle by<-10°. Age-specific target LL-TK alignment was calculated as published. Offset from target LL-TK was correlated to DJK magnitude and inclination. DJK types: severe (DJK<-20°), progressive (DJK increase>4.4°), symptomatic (reoperation or published disability thresholds of NDI ≥ 24 or mJOA≤14). Random forest identified factors associated with DJK. Means comparison tests assessed differences.Results
Included: 136 CD patients (61 ± 10 yr, 61%F). DJK rate was 30%. Postop offset from ideal LL-TK correlated with greater DJK angle (r = 0.428) and inclination of the distal end of the fusion construct (r = 0.244, both P < 0.02). Seven of the top 15 factors associated with DJK were radiographic, four surgical, and four clinical. Breakdown by type: severe (22%), progressive (24%), symptomatic (61%). Symptomatic had more posterior osteotomies than asymptomatic (P = 0.018). Severe had worse NDI and upper-cervical deformity (CL, C2 slope, C0-C2), as well as more posterior osteotomies than nonsevere (all P < 0.01). Progressive had greater malalignment both globally and in the cervical spine (all P < 0.03) than static. Each type had varying associated factors.Conclusion
Offset from age-specific alignment is associated with greater DJK and more anterior distal construct inclination, suggesting DJK may develop due to inappropriate realignment. Preoperative clinical and radiographic factors are associated with symptomatic and progressive DJK, suggesting the need for preoperative risk stratification.Level of Evidence: 3.Item Restricted Are mature smokers misinformed?(J Health Econ, 2009-03) Khwaja, Ahmed; Silverman, Dan; Sloan, Frank; Wang, YangWhile there are many reasons to continue to smoke in spite of its consequences for health, the concern that many smoke because they misperceive the risks of smoking remains a focus of public discussion and motivates tobacco control policies and litigation. In this paper we investigate the relative accuracy of mature smokers' risk perceptions about future survival, and a range of morbidities and disabilities. Using data from the survey on smoking (SOS) conducted for this research, we compare subjective beliefs elicited from the SOS with corresponding individual-specific objective probabilities estimated from the health and retirement study. Overall, consumers in the age group studied, 50-70, are not overly optimistic in their perceptions of health risk. If anything, smokers tend to be relatively pessimistic about these risks. The finding that smokers are either well informed or pessimistic regarding a broad range of health risks suggests that these beliefs are not pivotal in the decision to continue smoking. Although statements by the tobacco companies may have been misleading and thus encouraged some to start smoking, we find no evidence that systematic misinformation about the health consequences of smoking inhibits quitting.Item Open Access Assessing risk of breast cancer in an ethnically South-East Asia population (results of a multiple ethnic groups study).(BMC cancer, 2012-11-19) Gao, Fei; Machin, David; Chow, Khuan-Yew; Sim, Yu-Fan; Duffy, Stephen W; Matchar, David B; Goh, Chien-Hui; Chia, Kee-SengBackground
Gail and others developed a model (GAIL) using age-at-menarche, age-at-birth of first live child, number of previous benign breast biopsy examinations, and number of first-degree-relatives with breast cancer as well as baseline age-specific breast cancer risks for predicting the 5-year risk of invasive breast cancer for Caucasian women. However, the validity of the model for projecting risk in South-East Asian women is uncertain. We evaluated GAIL and attempted to improve its performance for Singapore women of Chinese, Malay and Indian origins.Methods
Data from the Singapore Breast Screening Programme (SBSP) are used. Motivated by lower breast cancer incidence in many Asian countries, we utilised race-specific invasive breast cancer and other cause mortality rates for Singapore women to produce GAIL-SBSP. By using risk factor information from a nested case-control study within SBSP, alternative models incorporating fewer then additional risk factors were determined. Their accuracy was assessed by comparing the expected cases (E) with the observed (O) by the ratio (E/O) and 95% confidence interval (CI) and the respective concordance statistics estimated.Results
From 28,883 women, GAIL-SBSP predicted 241.83 cases during the 5-year follow-up while 241 were reported (E/O=1.00, CI=0.88 to 1.14). Except for women who had two or more first-degree-relatives with breast cancer, satisfactory prediction was present in almost all risk categories. This agreement was reflected in Chinese and Malay, but not in Indian women. We also found that a simplified model (S-GAIL-SBSP) including only age-at-menarche, age-at-birth of first live child and number of first-degree-relatives performed similarly with associated concordance statistics of 0.5997. Taking account of body mass index and parity did not improve the calibration of S-GAIL-SBSP.Conclusions
GAIL can be refined by using national race-specific invasive breast cancer rates and mortality rates for causes other than breast cancer. A revised model containing only three variables (S-GAIL-SBSP) provides a simpler approach for projecting absolute risk of invasive breast cancer in South-East Asia women. Nevertheless its role in counseling the individual women regarding their risk of breast cancer remains problematical and needs to be validated in independent data.Item Open Access Association Between Comorbidities and Outcomes in Heart Failure Patients With and Without an Implantable Cardioverter-Defibrillator for Primary Prevention.(J Am Heart Assoc, 2015-08-06) Khazanie, Prateeti; Hellkamp, Anne S; Fonarow, Gregg C; Bhatt, Deepak L; Masoudi, Frederick A; Anstrom, Kevin J; Heidenreich, Paul A; Yancy, Clyde W; Curtis, Lesley H; Hernandez, Adrian F; Peterson, Eric D; Al-Khatib, Sana MBACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is associated with improved outcomes in patients with heart failure (HF), but whether this association holds among older patients with multiple comorbid illnesses and worse HF burden remains unclear. METHODS AND RESULTS: Using the National Cardiovascular Data Registry's ICD Registry and the Get With The Guidelines-Heart Failure (GWTG-HF) registry linked with Medicare claims, we examined outcomes associated with primary-prevention ICD versus no ICD among HF patients aged ≥65 years in clinical practice. We included patients with an ejection fraction ≤35% who received (ICD Registry) and who did not receive (GWTG-HF) an ICD. Compared with patients with an ICD, patients in the non-ICD group were older and more likely to be female and white. In matched cohorts, the 3-year adjusted mortality rate was lower in the ICD group versus the non-ICD group (46.7% versus 55.8%; adjusted hazard ratio [HR] 0.76; 95% CI 0.69 to 0.83). There was no associated difference in all-cause readmission (HR 0.99; 95% CI 0.92 to 1.08) but a lower risk of HF readmission (HR 0.88; 95% CI 0.80 to 0.97). When compared with no ICD, ICDs were also associated with better survival in patients with ≤3 comorbidities (HR 0.77; 95% CI 0.69 to 0.87) and >3 comorbidities (HR 0.77; 95% CI 0.64 to 0.93) and in patients with no hospitalization for HF (HR 0.75; 95% CI 0.65 to 0.86) and at least 1 prior HF hospitalization (HR 0.69; 95% CI 0.58 to 0.82). In subgroup analyses, there were no interactions between ICD and mortality risk for comorbidity burden (P=0.95) and for prior HF hospitalization (P=0.46). CONCLUSION: Among older HF patients, ICDs for primary prevention were associated with lower risk of mortality even among those with high comorbid illness burden and prior HF hospitalization.Item Open Access Association of Common Genetic Polymorphisms with Melanoma Patient IL-12p40 Blood Levels, Risk, and Outcomes.(J Invest Dermatol, 2015-09) Fang, Shenying; Wang, Yuling; Chun, Yun S; Liu, Huey; Ross, Merrick I; Gershenwald, Jeffrey E; Cormier, Janice N; Royal, Richard E; Lucci, Anthony; Schacherer, Christopher W; Reveille, John D; Chen, Wei; Sui, Dawen; Bassett, Roland L; Wang, Li-E; Wei, Qingyi; Amos, Christopher I; Lee, Jeffrey ERecent investigation has identified association of IL-12p40 blood levels with melanoma recurrence and patient survival. No studies have investigated associations of single-nucleotide polymorphisms (SNPs) with melanoma patient IL-12p40 blood levels or their potential contributions to melanoma susceptibility or patient outcome. In the current study, 818,237 SNPs were available for 1,804 melanoma cases and 1,026 controls. IL-12p40 blood levels were assessed among 573 cases (discovery), 249 cases (case validation), and 299 controls (control validation). SNPs were evaluated for association with log[IL-12p40] levels in the discovery data set and replicated in two validation data sets, and significant SNPs were assessed for association with melanoma susceptibility and patient outcomes. The most significant SNP associated with log[IL-12p40] was in the IL-12B gene region (rs6897260, combined P=9.26 × 10(-38)); this single variant explained 13.1% of variability in log[IL-12p40]. The most significant SNP in EBF1 was rs6895454 (combined P=2.24 × 10(-9)). A marker in IL12B was associated with melanoma susceptibility (rs3213119, multivariate P=0.0499; OR=1.50, 95% CI 1.00-2.24), whereas a marker in EBF1 was associated with melanoma-specific survival in advanced-stage patients (rs10515789, multivariate P=0.02; HR=1.93, 95% CI 1.11-3.35). Both EBF1 and IL12B strongly regulate IL-12p40 blood levels, and IL-12p40 polymorphisms may contribute to melanoma susceptibility and influence patient outcome.Item Open Access Association of Different Estimates of Renal Function With Cardiovascular Mortality and Bleeding in Atrial Fibrillation.(Journal of the American Heart Association, 2020-09) Hijazi, Ziad; Granger, Christopher B; Hohnloser, Stefan H; Westerbergh, Johan; Lindbäck, Johan; Alexander, John H; Keltai, Matyas; Parkhomenko, Alexander; López-Sendón, José L; Lopes, Renato D; Siegbahn, Agneta; Wallentin, LarsBackground We compared different methods of estimated glomerular filtration rate (eGFR) and their association with cardiovascular death and major bleeding in 14 980 patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Methods and Results eGFR was calculated using equations based on creatinine (Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and/or cystatin C (CKD-EPICysC and CKD-EPICysC+Creatinine). These 5 eGFR equations, as well as the individual variables that are used in these equations, were assessed for correlation and discriminatory ability for cardiovascular death and major bleeding. The median age was 70.0 years, and 35.6% were women. The median eGFR was highest with Cockcroft-Gault (74.1 mL/min) and CKD-EPICysC (74.2 mL/min), and lowest with Modification of Diet in Renal Disease (66.5 mL/min). Correlation between methods ranged from 0.49 (Cockroft-Gault and CKD-EPICysC) to 0.99 (Modification of Diet in Renal Disease and CKD-EPI). Among the eGFR equations, those based on cystatin C yielded the highest C indices for cardiovascular death and major bleeding: 0.628 (CKD-EPICysC) and 0.612 (CKD-EPICysC+Creatinine), respectively. A model based on the variables within the different eGFR equations (age, sex, weight, creatinine, and cystatin C) yielded the highest discriminatory value for both outcomes, with a C index of 0.673 and 0.656, respectively. Conclusions In patients with atrial fibrillation on anticoagulation, correlation between eGFR calculated using different methods varied substantially. Cystatin C-based eGFRs seem to provide the most robust information for predicting death and bleeding. A model based on the individual variables within the eGFR equations, however, provided the highest discriminatory value. Our findings may help refine risk stratification in patients with atrial fibrillation and define how renal function should be determined in future atrial fibrillation studies. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00412984.Item Open Access Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck.(Molecular carcinogenesis, 2018-06) Han, Peng; Liu, Hongliang; Shi, Qiong; Liu, Zhensheng; Troy, Jesse D; Lee, Walter T; Zevallos, Jose P; Li, Guojun; Sturgis, Erich M; Wei, QingyiSquamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0.001 and 0.001, respectively). After dividing the subjects by controls' median values of expression levels, we found a dose-dependent association between an increased risk of SCCHN and low expression levels of ERCC3 (adjusted OR, 1.75, and 95% CI: 1.26-2.42; Ptrend = 0.008) and XPA (adjusted OR, 1.88; 95% CI, 1.35-2.60; Ptrend = 0.001). We also identified a significant multiplicative interaction between smoking status and ERCC3 expression levels (P = 0.014). Finally, after integrating demographic and clinical variables, we found that the addition of ERCC3 and XPA expression levels to the model significantly improved the sensitivity of the expanded model on SCCHN risk. In conclusion, reduced protein expression levels of ERCC3 and XPA were associated with an increased risk of SCCHN. However, these results need to be confirmed in additional large studies.Item Open Access Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population.(Oncotarget, 2016-12) Zhou, Fei; Qiu, Li-Xin; Cheng, Lei; Wang, Meng-Yun; Li, Jin; Sun, Meng-Hong; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiInterleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Meta-analysis and genotype-mRNA expression correlation were performed to further validate positive associations. We found that an increased GCa risk was independently associated with rs1974226 (adjusted OR = 2.60, 95% CI = 1.27-5.32 for AA vs. GG + GA) and rs2275913 (adjusted OR = 1.33, 95% CI = 1.03-1.72 for GA + AA vs. GG), while a decreased GCa risk was independently associated with rs3819024 (adjusted OR = 0.72, 95% CI = 0.54-0.96 for GG vs. AA + AG). Additional meta-analyses confirmed the observed risk association with rs2275913. We also found that two IL-17 haplotypes (G-G-G-A-C) and (A-G-G-A-C) (in the order of rs1974226, rs2275913, rs3819024, rs4711998 and rs8193036) were associated with a reduced GCa risk (adjusted OR = 0.64, 95% CI = 0.46-0.89 and adjusted OR = 0.38, 95% CI = 0.17-0.81, respectively). However, the expression Quantitative Trait Locus (eQTL) analysis for the genotype-phenotype correlation did not find mRNA expression changes associated with either the genotypes. In conclusions, genetic variants of IL-17 are likely to be associated with risk of GCa, and additional larger studies with functional validation are needed to explore the molecular mechanisms underlying the observed associations.Item Open Access Bone scan positivity in non-metastatic, castrate-resistant prostate cancer: external validation study.(International braz j urol : official journal of the Brazilian Society of Urology, 2020-01) Johnston, Ashley W; Longo, Thomas A; Davis, Leah Gerber; Zapata, Daniel; Freedland, Stephen J; Routh, Jonathan CIntroduction
Tables predicting the probability of a positive bone scan in men with non-metastatic, castrate-resistant prostate cancer have recently been reported. We performed an external validation study of these bone scan positivity tables.Materials and methods
We performed a retrospective cohort study of patients seen at a tertiary care medical center (1996-2012) to select patients with non-metastatic, castrate-resistant prostate cancer. Abstracted data included demographic, anthropometric, and disease-specific data such as patient race, BMI, PSA kinetics, and primary treatment. Primary outcome was metastasis on bone scan. Multivariable logistic regression was performed using generalized estimating equations to adjust for repeated measures. Risk table performance was assessed using ROC curves.Results
We identified 6.509 patients with prostate cancer who had received hormonal therapy with a post-hormonal therapy PSA ≥2ng/mL, 363 of whom had non-metastatic, castrate-resistant prostate cancer. Of these, 187 patients (356 bone scans) had calculable PSA kinetics and ≥1 bone scan. Median follow-up after castrate-resistant prostate cancer diagnosis was 32 months (IQR: 19-48). There were 227 (64%) negative and 129 (36%) positive bone scans. On multivariable analysis, higher PSA at castrate-resistant prostate cancer (4.67 vs. 4.4ng/mL, OR=0.57, P=0.02), shorter time from castrate-resistant prostate cancer to scan (7.9 vs. 14.6 months, OR=0.97, P=0.006) and higher PSA at scan (OR=2.91, P<0.0001) were significantly predictive of bone scan positivity. The AUC of the previously published risk tables for predicting scan positivity was 0.72.Conclusion
Previously published risk tables predicted bone scan positivity in men with non-metastatic, castrate-resistant prostate cancer with reasonable accuracy.Item Open Access Cardiovascular disease, risk factors, and health behaviors among cancer survivors and spouses: A MEPS Study.(Cancer medicine, 2020-09) Song, Lixin; Guan, Ting; Guo, Peiran; Song, Fengyu; Van Houtven, Courtney; Tan, Xianming; Keyserling, Thomas CPurpose
The purpose of this study was to examine the prevalences of CVD, CVD risk factors. and health behaviors among cancer survivor-spouse dyads, assess how these prevalences differ by role (survivor vs spouse) and gender, and report congruences in health behaviors between survivors and their spouses.Methods
We identified 1026 survivor-spouse dyads from the 2010-2015 Medical Expenditure Panel Survey. We used weighted multivariable logistic and linear regressions to analyze the data related to CVD, CVD risk factors, and health behaviors.Results
Survivors and spouses reported high prevalences of CVD and CVD risk factors but low engagement in healthy behaviors, including non-smoking, physical activity, and maintaining a healthy weight (proxy for healthy diet). Gender and role differences were significantly related to the prevalence of CVD, CVD risk factors, and health behaviors among survivors and spouses. From 39% to 88% of survivors and spouses were congruent in their current smoking status, physical activity engagement/disengagement, and BMI.Conclusion
Cancer survivors and spouses have high rates of CVD and CVD risk factors and poor engagement in healthful lifestyle behaviors. A high proportion of survivors and spouses were congruent in their current smoking status, physical activity engagement/disengagement, and BMI. Effective lifestyle interventions are needed for this high-risk population. Couple-focused interventions may be well-suited for these dyads and warrant further study.Implications for cancer survivors
Both cancer survivors and their spouses need to be non-moking, more physically active, and maintain normal BMI in order to reduce their high risk of CVD and CVD risk factors.Item Open Access Caring for Alaska Native prostate cancer survivors in primary care: a survey of Alaska Tribal Health System providers.(Int J Circumpolar Health, 2014) Tilburt, Jon C; Kelley, Stacy; DeCourtney, Christine A; Humeniuk, Katherine M; Latini, Jerilyn; Kim, Simon PBACKGROUND: Little is known about the constraints of optimizing health care for prostate cancer survivors in Alaska primary care. OBJECTIVE: To describe the experiences and attitudes of primary care providers within the Alaska Tribal Health System (ATHS) regarding the care of prostate cancer survivors. DESIGN: In late October 2011, we emailed a 22-item electronic survey to 268 ATHS primary care providers regarding the frequency of Prostate Specific Antigen (PSA) monitoring for a hypothetical prostate cancer survivor; who should be responsible for the patient's life-long prostate cancer surveillance; who should support the patient's emotional and medical needs as a survivor; and providers' level of comfort addressing recurrence monitoring, erectile dysfunction, urinary incontinence, androgen deprivation therapy, and emotional needs. We used simple logistic regression to examine the association between provider characteristics and their responses to the survivorship survey items. RESULTS: Of 221 individuals who were successfully contacted, a total of 114 responded (52% response rate). Most ATHS providers indicated they would order a PSA test every 12 months (69%) and believed that, ideally, the hypothetical patient's primary care provider should be responsible for his life-long prostate cancer surveillance (60%). Most providers reported feeling either "moderately" or "very" comfortable addressing topics such as prostate cancer recurrence (59%), erectile dysfunction (64%), urinary incontinence (63%), and emotional needs (61%) with prostate cancer survivors. These results varied somewhat by provider characteristics including female sex, years in practice, and the number of prostate cancer survivors seen in their practice. CONCLUSIONS: These data suggest that most primary care providers in Alaska are poised to assume the care of prostate cancer survivors locally. However, we also found that large minorities of providers do not feel confident in their ability to manage common issues in prostate cancer survivorship, implying that continued access to specialists with more expert knowledge would be beneficial.Item Open Access Changes in hospitalisation and surgical procedures among the oldest-old: a follow-up study of the entire Danish 1895 and 1905 cohorts from ages 85 to 99 years.(Age Ageing, 2013-07) Oksuzyan, Anna; Jeune, Bernard; Juel, Knud; Vaupel, James W; Christensen, KaareOBJECTIVE: to examine whether the Danish 1905 cohort members had more active hospital treatment than the 1895 cohort members from ages 85 to 99 years and whether it results in higher in-hospital and post-operative mortality. METHODS: in the present register-based follow-up study the complete Danish birth cohorts born in 1895 (n = 12,326) and 1905 (n = 15,477) alive and residing in Denmark at the age of 85 were followed from ages 85 to 99 years with regard to hospitalisations and all-cause and cause-specific surgical procedures, as well as in-hospital and post-operative mortality. RESULTS: the 1905 cohort members had more frequent hospital admissions and operations, but they had a shorter length of hospital stay than the 1895 cohort at all ages from 85 to 99 years. The increase in primary prosthetic replacements of hip joint was observed even within the 1895 cohort: no patients were operated at ages 85-89 years versus 2.2-3.6% at ages 95-99 years. Despite increased hospitalisation and operation rates, there was no increase in post-operative and in-hospital mortality rates in the 1905 cohort. These patterns were similar among men and women. CONCLUSIONS: the observed patterns are compatible with more active treatment of the recent cohorts of old-aged persons and reduced age inequalities in the Danish healthcare system. No increase in post-operative mortality suggests that the selection of older patients eligible for a surgical treatment is likely to be based on the health status of old-aged persons and the safety of surgical procedures rather than chronological age.