Browsing by Subject "Risk Factors"
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Item Open Access A case-control study of airways obstruction among construction workers.(Am J Ind Med, 2015-10) Dement, John; Welch, Laura; Ringen, Knut; Quinn, Patricia; Chen, Anna; Haas, ScottBACKGROUND: While smoking is the major cause of chronic obstructive pulmonary disease (COPD), occupational exposures to vapors, gases, dusts, and fumes (VGDF) increase COPD risk. This case-control study estimated the risk of COPD attributable to occupational exposures among construction workers. METHODS: The study population included 834 cases and 1243 controls participating in a national medical screening program for older construction workers between 1997 and 2013. Qualitative exposure indices were developed based on lifetime work and exposure histories. RESULTS: Approximately 18% (95% CI = 2-24%) of COPD risk can be attributed to construction-related exposures, which are additive to the risk contributed by smoking. A measure of all VGDF exposures combined was a strong predictor of COPD risk. CONCLUSIONS: Construction workers are at increased risk of COPD as a result of broad and complex effects of many exposures acting independently or interactively. Control methods should be implemented to prevent worker exposures, and smoking cessation should be promoted.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 cohort study of 4,190 patients treated with low-intensity pulsed ultrasound (LIPUS): findings in the elderly versus all patients.(BMC Musculoskelet Disord, 2015-03-01) Zura, Robert; Mehta, Samir; Rocca, Gregory J Della; Jones, John; Steen, R GrantBACKGROUND: Patient age is one of many potential risk factors for fracture nonunion. Our hypothesis is that older patients (≥ 60) with fracture risk factors treated with low-intensity pulsed ultrasound (LIPUS) have similar heal rate (HR) to the population as a whole. We evaluate the impact of age in conjunction with other risk factors on HR in LIPUS-treated patients with fresh fracture (≤ 90 days old). METHODS: The Exogen Bone Healing System is a LIPUS device approved in 1994 to accelerate healing of fresh fracture. After approval, the FDA required a Post-Market Registry to assess performance. Patient data collected from October 1994 until October 1998 were individually reviewed and validated by a registered nurse. Four distinct data elements were required to report a patient: date fracture occurred; date treatment began; date treatment ended; and a dichotomous outcome of healed v. failed, by clinical and radiological criteria. Data were used to calculate two derived variables; days to treatment (DTT) and days on treatment (DOT). Every validated fresh fracture patient with DTT, DOT, and outcome is reported. RESULTS: The validated registry had 5,765 patients with fresh fracture; 73% (N = 4,190) are reported, while 13% of patients were lost to follow-up, 11% withdrew or were non-compliant, and 3% died or are missing outcome. Among treatment-compliant patients, HR was 96.2%. Logistic estimates of the odds ratio for healing are equivalent for patients age 30 to 79 years and all age cohorts had a HR > 94%. Open fracture, current smoking, diabetes, vascular insufficiency, osteoporosis, cancer, rheumatoid arthritis, and prescription NSAIDs all reduced HR, but older patients (≥ 60) had similar HRs to the population as a whole. DTT was significantly shorter for patients who healed (p < 0.0001). CONCLUSIONS: Comorbid conditions in conjunction with aging can reduce fracture HR. Patients with fracture who used LIPUS had a 96% HR, whereas the expected HR averages 93%. Time to treatment was significantly shorter among patients who healed (p < 0.0001), suggesting that it is beneficial to begin LIPUS treatment early. Older patients (≥ 60) with fracture risk factors treated with LIPUS exhibit similar heal rates to the population as a whole.Item Open Access A dimensional approach to understanding severity estimates and risk correlates of marijuana abuse and dependence in adults.(International journal of methods in psychiatric research, 2012-06) Wu, Li-Tzy; Woody, George E; Yang, Chongming; Pan, Jeng-Jong; Reeve, Bryce B; Blazer, Dan GWhile item response theory (IRT) research shows a latent severity trait underlying response patterns of substance abuse and dependence symptoms, little is known about IRT-based severity estimates in relation to clinically relevant measures. In response to increased prevalences of marijuana-related treatment admissions, an elevated level of marijuana potency, and the debate on medical marijuana use, we applied dimensional approaches to understand IRT-based severity estimates for marijuana use disorders (MUDs) and their correlates while simultaneously considering gender- and race/ethnicity-related differential item functioning (DIF). Using adult data from the 2008 National Survey on Drug Use and Health (N = 37,897), Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for MUDs among past-year marijuana users were examined by IRT, logistic regression, and multiple indicators-multiple causes (MIMIC) approaches. Among 6917 marijuana users, 15% met criteria for a MUD; another 24% exhibited subthreshold dependence. Abuse criteria were highly correlated with dependence criteria (correlation = 0.90), indicating unidimensionality; item information curves revealed redundancy in multiple criteria. MIMIC analyses showed that MUD criteria were positively associated with weekly marijuana use, early marijuana use, other substance use disorders, substance abuse treatment, and serious psychological distress. African Americans and Hispanics showed higher levels of MUDs than Whites, even after adjusting for race/ethnicity-related DIF. The redundancy in multiple criteria suggests an opportunity to improve efficiency in measuring symptom-level manifestations by removing low-informative criteria. Elevated rates of MUDs among African Americans and Hispanics require research to elucidate risk factors and improve assessments of MUDs for different racial/ethnic groups.Item Open Access A functional NQO1 609C>T polymorphism and risk of gastrointestinal cancers: a meta-analysis.(PloS one, 2012-01-17) Yu, Hongping; Liu, Hongliang; Wang, Li-E; Wei, QingyiThe functional polymorphism (rs1800566) in the NQO1 gene, a 609C>T substitution, leading to proline-to-serine amino-acid and enzyme activity changes, has been implicated in cancer risk, but individually published studies showed inconclusive results.We performed a meta-analysis of 20 publications with a total of 5,491 cases and 5,917 controls, mainly on gastrointestinal (GI) cancers. We summarized the data on the association between the NQO1 609C>T polymorphism and risk of GI cancers and performed subgroup analyses by ethnicity, cancer site, and study quality. We found that the variant CT heterozygous and CT/TT genotypes of the NQO1 609 C>T polymorphism were associated with a modestly increased risk of GI cancers (CT vs. CC: OR = 1.10, 95% CI = 1.01 - 1.19, P(heterogeneity) = 0.27, I(2) = 0.15; CT/TT vs. CC: OR = 1.11, 95%CI = 1.02 - 1.20, P(heterogeneity) = 0.14; I(2) = 0.27). Following further stratified analyses, the increased risk was only observed in subgroups of Caucasians, colorectal cancer in Caucasians, and high quality studies.This meta-analysis suggests that the NQO1 609T allele is a low-penetrance risk factor for GI cancers. Although the effect on GI cancers may be modified by ethnicity and cancer sites, small sample seizes of the subgroup analyses suggest that further larger studies are needed, especially for non-colorectal GI cancers in Caucasians and GI cancers in Asians.Item Open Access A Functional Polymorphism (rs2494752) in the AKT1 Promoter Region and Gastric Adenocarcinoma Risk in an Eastern Chinese Population.(Scientific reports, 2016-01-28) Wang, Meng-Yun; He, Jing; Zhu, Mei-Ling; Teng, Xiao-Yan; Li, Qiao-Xin; Sun, Meng-Hong; Wang, Xiao-Feng; Yang, Ya-Jun; Wang, Jiu-Cun; Jin, Li; Wang, Ya-Nong; Wei, Qing-YiAKT is an important signal transduction protein that plays a crucial role in cancer development. Therefore, we evaluated associations between single nucleotide polymorphisms (SNPs) in the AKT promoter region and gastric cancer (GCa) risk in a case-control study of 1,110 GCa patients and 1,114 matched cancer-free controls. We genotyped five SNPs (AKT1 rs2494750G >C, AKT1 rs2494752A >G, AKT1 rs10138227C >T, AKT2 rs7254617G>A and AKT2 rs2304186G >T) located in the 5' upstream regulatory, first intron or promoter regions. In the logistic regression analysis, a significantly elevated GCa risk was associated with the rs2494752 AG/GG variant genotypes (adjusted odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.02-1.42) under a dominant genetic model, and this risk was more evident in subgroups of ever drinkers. The luciferase reporter assay showed that the rs2494752 G allele significantly increased luciferase activity. Our results suggest that the potentially functional AKT1 rs2494752 SNP may affect GCa susceptibility, likely by modulating the AKT1 promoter transcriptional activity. Larger, independent studies are warranted to validate our findings.Item Open Access A functional polymorphism in the 5HTR2C gene associated with stress responses also predicts incident cardiovascular events.(PLoS One, 2013) Brummett, Beverly H; Babyak, Michael A; Jiang, Rong; Shah, Svati H; Becker, Richard C; Haynes, Carol; Chryst-Ladd, Megan; Craig, Damian M; Hauser, Elizabeth R; Siegler, Ilene C; Kuhn, Cynthia M; Singh, Abanish; Williams, Redford BPreviously we have shown that a functional nonsynonymous single nucleotide polymorphism (rs6318) of the 5HTR2C gene located on the X-chromosome is associated with hypothalamic-pituitary-adrenal axis response to a stress recall task, and with endophenotypes associated with cardiovascular disease (CVD). These findings suggest that individuals carrying the rs6318 Ser23 C allele will be at higher risk for CVD compared to Cys23 G allele carriers. The present study examined allelic variation in rs6318 as a predictor of coronary artery disease (CAD) severity and a composite endpoint of all-cause mortality or myocardial infarction (MI) among Caucasian participants consecutively recruited through the cardiac catheterization laboratory at Duke University Hospital (Durham, NC) as part of the CATHGEN biorepository. Study population consisted of 6,126 Caucasian participants (4,036 [65.9%] males and 2,090 [34.1%] females). A total of 1,769 events occurred (1,544 deaths and 225 MIs; median follow-up time = 5.3 years, interquartile range = 3.3-8.2). Unadjusted Cox time-to-event regression models showed, compared to Cys23 G carriers, males hemizygous for Ser23 C and females homozygous for Ser23C were at increased risk for the composite endpoint of all-cause death or MI: Hazard Ratio (HR) = 1.47, 95% confidence interval (CI) = 1.17, 1.84, p = .0008. Adjusting for age, rs6318 genotype was not related to body mass index, diabetes, hypertension, dyslipidemia, smoking history, number of diseased coronary arteries, or left ventricular ejection fraction in either males or females. After adjustment for these covariates the estimate for the two Ser23 C groups was modestly attenuated, but remained statistically significant: HR = 1.38, 95% CI = 1.10, 1.73, p = .005. These findings suggest that this functional polymorphism of the 5HTR2C gene is associated with increased risk for CVD mortality and morbidity, but this association is apparently not explained by the association of rs6318 with traditional risk factors or conventional markers of atherosclerotic disease.Item Open Access A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.(BMC cancer, 2011-01) Zhou, Keke; Hu, Dezhi; Lu, Juan; Fan, Weiwei; Liu, Hongliang; Chen, Hongyan; Chen, Gong; Wei, Qingyi; Du, Guhong; Mao, Ying; Lu, Daru; Zhou, LiangfuBACKGROUND: The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression. Recently, the APE1/Ref-1 promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of APE1/Ref-1 in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes. METHODS: The APE1/Ref-1 -141T/G polymorphism was analyzed in a case-control study including 766 glioma patients (among them 241 glioblastoma, 284 astrocytomas except for glioblastoma and 241 other gliomas) and 824 cancer-free controls from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele-specific MALDI-TOF mass spectrometry assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. A test of trend was calculated using the genotype as an ordinal variable in the regression model. For each statistically significant association identified, we estimated the false positive reporting probability (FPRP). FPRP values less than 0.2 were consider to indicate robust associations. RESULTS: The significant association between the APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk (OR = 0.80, 95% CI = 0.65-0.98, P = 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, P = 0.012), compared with the TT homozygote. This result remained robust given the prior probabilities of 25% (FPRP = 0.052) and 10% (FPRP = 0.140), but not with a prior probability of 1% (FPRP = 0.643). The P-associated with the trend test was 0.014. CONCLUSIONS: Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.Item Open Access A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium.(PLoS genetics, 2011-03-17) McKay, James D; Truong, Therese; Gaborieau, Valerie; Chabrier, Amelie; Chuang, Shu-Chun; Byrnes, Graham; Zaridze, David; Shangina, Oxana; Szeszenia-Dabrowska, Neonila; Lissowska, Jolanta; Rudnai, Peter; Fabianova, Eleonora; Bucur, Alexandru; Bencko, Vladimir; Holcatova, Ivana; Janout, Vladimir; Foretova, Lenka; Lagiou, Pagona; Trichopoulos, Dimitrios; Benhamou, Simone; Bouchardy, Christine; Ahrens, Wolfgang; Merletti, Franco; Richiardi, Lorenzo; Talamini, Renato; Barzan, Luigi; Kjaerheim, Kristina; Macfarlane, Gary J; Macfarlane, Tatiana V; Simonato, Lorenzo; Canova, Cristina; Agudo, Antonio; Castellsagué, Xavier; Lowry, Ray; Conway, David I; McKinney, Patricia A; Healy, Claire M; Toner, Mary E; Znaor, Ariana; Curado, Maria Paula; Koifman, Sergio; Menezes, Ana; Wünsch-Filho, Victor; Neto, José Eluf; Garrote, Leticia Fernández; Boccia, Stefania; Cadoni, Gabriella; Arzani, Dario; Olshan, Andrew F; Weissler, Mark C; Funkhouser, William K; Luo, Jingchun; Lubiński, Jan; Trubicka, Joanna; Lener, Marcin; Oszutowska, Dorota; Schwartz, Stephen M; Chen, Chu; Fish, Sherianne; Doody, David R; Muscat, Joshua E; Lazarus, Philip; Gallagher, Carla J; Chang, Shen-Chih; Zhang, Zuo-Feng; Wei, Qingyi; Sturgis, Erich M; Wang, Li-E; Franceschi, Silvia; Herrero, Rolando; Kelsey, Karl T; McClean, Michael D; Marsit, Carmen J; Nelson, Heather H; Romkes, Marjorie; Buch, Shama; Nukui, Tomoko; Zhong, Shilong; Lacko, Martin; Manni, Johannes J; Peters, Wilbert HM; Hung, Rayjean J; McLaughlin, John; Vatten, Lars; Njølstad, Inger; Goodman, Gary E; Field, John K; Liloglou, Triantafillos; Vineis, Paolo; Clavel-Chapelon, Francoise; Palli, Domenico; Tumino, Rosario; Krogh, Vittorio; Panico, Salvatore; González, Carlos A; Quirós, J Ramón; Martínez, Carmen; Navarro, Carmen; Ardanaz, Eva; Larrañaga, Nerea; Khaw, Kay-Tee; Key, Timothy; Bueno-de-Mesquita, H Bas; Peeters, Petra HM; Trichopoulou, Antonia; Linseisen, Jakob; Boeing, Heiner; Hallmans, Göran; Overvad, Kim; Tjønneland, Anne; Kumle, Merethe; Riboli, Elio; Välk, Kristjan; Vooder, Tõnu; Metspalu, Andres; Zelenika, Diana; Boland, Anne; Delepine, Marc; Foglio, Mario; Lechner, Doris; Blanché, Hélène; Gut, Ivo G; Galan, Pilar; Heath, Simon; Hashibe, Mia; Hayes, Richard B; Boffetta, Paolo; Lathrop, Mark; Brennan, PaulGenome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.Item Open Access A memory-based model of posttraumatic stress disorder: evaluating basic assumptions underlying the PTSD diagnosis.(Psychol Rev, 2008-10) Rubin, David C; Berntsen, Dorthe; Bohni, Malene KlindtIn the mnemonic model of posttraumatic stress disorder (PTSD), the current memory of a negative event, not the event itself, determines symptoms. The model is an alternative to the current event-based etiology of PTSD represented in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000). The model accounts for important and reliable findings that are often inconsistent with the current diagnostic view and that have been neglected by theoretical accounts of the disorder, including the following observations. The diagnosis needs objective information about the trauma and peritraumatic emotions but uses retrospective memory reports that can have substantial biases. Negative events and emotions that do not satisfy the current diagnostic criteria for a trauma can be followed by symptoms that would otherwise qualify for PTSD. Predisposing factors that affect the current memory have large effects on symptoms. The inability-to-recall-an-important-aspect-of-the-trauma symptom does not correlate with other symptoms. Loss or enhancement of the trauma memory affects PTSD symptoms in predictable ways. Special mechanisms that apply only to traumatic memories are not needed, increasing parsimony and the knowledge that can be applied to understanding PTSD.Item Open Access A model for predicting the risk of de novo stress urinary incontinence in women undergoing pelvic organ prolapse surgery.(Obstetrics and gynecology, 2014-02) Jelovsek, J Eric; Chagin, Kevin; Brubaker, Linda; Rogers, Rebecca G; Richter, Holly E; Arya, Lily; Barber, Matthew D; Shepherd, Jonathan P; Nolen, Tracy L; Norton, Peggy; Sung, Vivian; Menefee, Shawn; Siddiqui, Nazema; Meikle, Susan F; Kattan, Michael W; Pelvic Floor Disorders NetworkTo construct and validate a prediction model for estimating the risk of de novo stress urinary incontinence (SUI) after vaginal pelvic organ prolapse (POP) surgery and compare it with predictions using preoperative urinary stress testing and expert surgeons' predictions.Using the data set (n=457) from the Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial, a model using 12 clinical preoperative predictors of de novo SUI was constructed. De novo SUI was determined by Pelvic Floor Distress Inventory responses through 12 months postoperatively. After fitting the multivariable logistic regression model using the best predictors, the model was internally validated with 1,000 bootstrap samples to obtain bias-corrected accuracy using a concordance index. The model's predictions were also externally validated by comparing findings against actual outcomes using Colpopexy and Urinary Reduction Efforts trial patients (n=316). The final model's performance was compared with experts using a test data set of 32 randomly chosen Outcomes Following Vaginal Prolapse Repair and Midurethral Sling trial patients through comparison of the model's area under the curve against: 1) 22 experts' predictions; and 2) preoperative prolapse reduction stress testing.A model containing seven predictors discriminated between de novo SUI status (concordance index 0.73, 95% confidence interval [CI] 0.65-0.80) in Outcomes Following Vaginal Prolapse Repair and Midurethral Sling participants and outperformed expert clinicians (area under the curve 0.72 compared with 0.62, P<.001) and preoperative urinary stress testing (area under the curve 0.72 compared with 0.54, P<.001). The concordance index for Colpopexy and Urinary Reduction Efforts trial participants was 0.62 (95% CI 0.56-0.69).This individualized prediction model for de novo SUI after vaginal POP surgery is valid and outperforms preoperative stress testing, prediction by experts, and preoperative reduction cough stress testing. An online calculator is provided for clinical use.III.Item Open Access A multicenter retrospective cohort study on predicting the risk for amiodarone pulmonary toxicity.(BMC pulmonary medicine, 2022-04) Kwok, Wang Chun; Ma, Ting Fung; Chan, Johnny Wai Man; Pang, Herbert H; Ho, James Chung ManBackground
Amiodarone is one of the most commonly used anti-arrhythmic agents. Amiodarone pulmonary toxicity is a potentially fatal adverse effect associated with amiodarone use. Previous studies on the epidemiology and risk factors for amiodarone pulmonary toxicity showed diverse results.Methods
A multicenter retrospective cohort study was conducted to identify clinic-epidemiologic markers associated with amiodarone pulmonary toxicity for development of a prediction rule. Patients taking amiodarone who were managed in 3 centres in Hong Kong from 2005 to 2015 were included in this study. Penalized logistic regression was used to model the outcome as it is rare.Results
A total of 34 cases with amiodarone pulmonary toxicity were identified among 1786 patients taking amiodarone for at least 90 days from 2005 to 2015. The incidence of amiodarone pulmonary toxicity was estimated to be 1.9%. The risk factors for amiodarone pulmonary toxicity included advanced age (OR 1.047, 95% CI 1.010-1.085, p = 0.013), ventricular arrhythmia (OR 2.703, 95% CI 1.053-6.935, p = 0.039), underlying lung disease (OR 2.511, 95% CI 1.146-5.501, p = 0.021) and cumulative dose of amiodarone (OR 4.762, 95% CI 1.310-17.309 p = 0.018).Conclusions
The incidence of amiodarone pulmonary toxicity in Chinese patients in Hong Kong is estimated to be 1.9% in this study. Age, underlying lung disease, ventricular arrhythmia and cumulative dose of amiodarone are associated with the development of amiodarone pulmonary toxicity. A prediction rule was developed to inform the risk of developing amiodarone pulmonary toxicity.Item Open Access A neural biomarker of psychological vulnerability to future life stress.(Neuron, 2015-02-04) Swartz, J; Knodt, A; Radtke, S; Hariri, AWe all experience a host of common life stressors such as the death of a family member, medical illness, and financial uncertainty. While most of us are resilient to such stressors, continuing to function normally, for a subset of individuals, experiencing these stressors increases the likelihood of developing treatment-resistant, chronic psychological problems, including depression and anxiety. It is thus paramount to identify predictive markers of risk, particularly those reflecting fundamental biological processes that can be targets for intervention and prevention. Using data from a longitudinal study of 340 healthy young adults, we demonstrate that individual differences in threat-related amygdala reactivity predict psychological vulnerability to life stress occurring as much as 1 to 4 years later. These results highlight a readily assayed biomarker, threat-related amygdala reactivity, which predicts psychological vulnerability to commonly experienced stressors and represents a discrete target for intervention and prevention.Item Open Access A new predictive model for an improved respiratory isolation strategy in HIV-infected patients with PTB.(The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 2014-07) Carugati, M; Schiroli, C; Zanini, F; Vanoni, N; Galli, M; Adorni, F; Franzetti, FSetting
Luigi Sacco Hospital, Milan, Italy, 1 January 2000-31 December 2010.Objectives
To develop a predictive score for identifying human immunodeficiency virus (HIV) infected patients with pulmonary tuberculosis (PTB).Design
Retrospective study based on the medical charts of HIV-infected patients admitted consecutively on presumption of PTB. Patients with culture-positive TB were included in the TB group. Culture-negative subjects formed the non-TB group. Risk factors for PTB were identified and a predictive model was developed. The diagnostic test accuracy of the derived score and that of previously developed scores were analysed.Results
A total of 65 patients were included in the TB group and 505 subjects in the non-TB group. An eight-variable model (age, origin, alcohol use, respiratory rate, weight loss, haemoglobin, white blood cell count, typical chest X-ray) was derived. When compared with the different scores, this model showed the greatest area under the receiver operating characteristic curve (0.880). This score was the only one to present a negative likelihood ratio of <0.2, which is the threshold for giving strong diagnostic evidence against TB.Conclusions
This model may be useful in predicting PTB in HIV patients in low-endemic countries. A validation study is necessary.Item Open Access A Novel Genetic Variant in Long Non-coding RNA Gene NEXN-AS1 is Associated with Risk of Lung Cancer.(Scientific reports, 2016-10-07) Yuan, Hua; Liu, Hongliang; Liu, Zhensheng; Owzar, Kouros; Han, Younghun; Su, Li; Wei, Yongyue; Hung, Rayjean J; McLaughlin, John; Brhane, Yonathan; Brennan, Paul; Bickeboeller, Heike; Rosenberger, Albert; Houlston, Richard S; Caporaso, Neil; Landi, Maria Teresa; Heinrich, Joachim; Risch, Angela; Christiani, David C; Gümüş, Zeynep H; Klein, Robert J; Amos, Christopher I; Wei, QingyiLung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. We performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium in populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10-7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University and deCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11-1.24; P = 8.31 × 10-9). In further in silico analysis, rs114020893 was predicted to change the secondary structure of the lncRNA. Our finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.Item Open Access A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls.(Arthritis Res Ther, 2016-04-12) Bartlett, David B; Connelly, Margery A; AbouAssi, Hiba; Bateman, Lori A; Tune, K Noelle; Huebner, Janet L; Kraus, Virginia B; Winegar, Deborah A; Otvos, James D; Kraus, William E; Huffman, Kim MBACKGROUND: RA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA. METHODS: Plasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance. RESULTS: On average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1β, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = -0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all). CONCLUSIONS: GlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.Item Open Access A prospective neurosurgical registry evaluating the clinical care of traumatic brain injury patients presenting to Mulago National Referral Hospital in Uganda.(PloS one, 2017-01) Kuo, Benjamin J; Vaca, Silvia D; Vissoci, Joao Ricardo Nickenig; Staton, Catherine A; Xu, Linda; Muhumuza, Michael; Ssenyonjo, Hussein; Mukasa, John; Kiryabwire, Joel; Nanjula, Lydia; Muhumuza, Christine; Rice, Henry E; Grant, Gerald A; Haglund, Michael MBackground
Traumatic Brain Injury (TBI) is disproportionally concentrated in low- and middle-income countries (LMICs), with the odds of dying from TBI in Uganda more than 4 times higher than in high income countries (HICs). The objectives of this study are to describe the processes of care and determine risk factors predictive of poor outcomes for TBI patients presenting to Mulago National Referral Hospital (MNRH), Kampala, Uganda.Methods
We used a prospective neurosurgical registry based on Research Electronic Data Capture (REDCap) to systematically collect variables spanning 8 categories. Univariate and multivariate analysis were conducted to determine significant predictors of mortality.Results
563 TBI patients were enrolled from 1 June- 30 November 2016. 102 patients (18%) received surgery, 29 patients (5.1%) intended for surgery failed to receive it, and 251 patients (45%) received non-operative management. Overall mortality was 9.6%, which ranged from 4.7% for mild and moderate TBI to 55% for severe TBI patients with GCS 3-5. Within each TBI severity category, mortality differed by management pathway. Variables predictive of mortality were TBI severity, more than one intracranial bleed, failure to receive surgery, high dependency unit admission, ventilator support outside of surgery, and hospital arrival delayed by more than 4 hours.Conclusions
The overall mortality rate of 9.6% in Uganda for TBI is high, and likely underestimates the true TBI mortality. Furthermore, the wide-ranging mortality (3-82%), high ICU fatality, and negative impact of care delays suggest shortcomings with the current triaging practices. Lack of surgical intervention when needed was highly predictive of mortality in TBI patients. Further research into the determinants of surgical interventions, quality of step-up care, and prolonged care delays are needed to better understand the complex interplay of variables that affect patient outcome. These insights guide the development of future interventions and resource allocation to improve patient outcomes.Item Open Access A protocol to evaluate the efficacy, perceptions, and cost of a cholesterol packaging approach to improve medication adherence.(Contemporary clinical trials, 2014-09) Zullig, Leah L; Pathman, Joshua; Melnyk, S Dee; Brown, Jamie N; Sanders, Linda L; Koropchak, Celine; Howard, Teresa; Danus, Susanne; McCant, Felicia; Bosworth, Hayden BPurpose
Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable risk factor for cardiovascular disease (CVD), a leading cause of death in the United States. Despite clinical practice guidelines aimed at facilitating LDL-C control, many Veterans do not achieve guideline-recommended LDL-C levels.Methods
We describe a study focused on VA healthcare system users at risk for CVD (i.e., LDL-C level >130 mg/dl and/or <80% cholesterol pill refill adherence in the last 12 months). We are conducting a two and a half year randomized controlled trial (i.e., intervention administered over 12 months) among Veterans with uncontrolled cholesterol receiving care at select VA-affiliated primary care clinics in North Carolina. We anticipate enrolling 250 diverse patients (10% women; 40% African American). Patients are randomized to an educational control group or intervention group. Intervention group participants' medication is provided in special blister packaging labeled for daily use that includes reminders; MeadWestvaco Corporation's pre-filled DosePak® contains standard doses of statins in accordance with the existing prescriptions.Conclusions
Pre-filled blister packaging may provide an inexpensive solution to improve medication adherence. Our study enrolls a diverse sample and provides information about whether an adherence packaging intervention can: 1) improve medication adherence; 2) improve patients' LDL-C levels; 3) be well received by patients and providers; and 4) provide a cost effective solution to improve medication adherence.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 Unknown A U-shaped Association Between Blood Pressure and Cognitive Impairment in Chinese Elderly.(Journal of the American Medical Directors Association, 2017-02) Lv, Yue-Bin; Zhu, Peng-Fei; Yin, Zhao-Xue; Kraus, Virginia Byers; Threapleton, Diane; Chei, Choy-Lye; Brasher, Melanie Sereny; Zhang, Juan; Qian, Han-Zhu; Mao, Chen; Matchar, David Bruce; Luo, Jie-Si; Zeng, Yi; Shi, Xiao-MingObjectives
Higher or lower blood pressure may relate to cognitive impairment, whereas the relationship between blood pressure and cognitive impairment among the elderly is not well-studied. The study objective was to determine whether blood pressure is associated with cognitive impairment in the elderly, and, if so, to accurately describe the association.Design
Cross-sectional data from the sixth wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 2011.Setting
Community-based setting in longevity areas in China.Participants
A total of 7144 Chinese elderly aged 65 years and older were included in the sample.Measures
Systolic blood pressures (SBP) and diastolic blood pressures (DBP) were measured, pulse pressure (PP) was calculated as (SBP) - (DBP) and mean arterial pressures (MAP) was calculated as 1/3(SBP) + 2/3(DBP). Cognitive function was assessed via a validated Mini-Mental State Examination (MMSE).Results
Based on the results of generalized additive models (GAMs), U-shaped associations were identified between cognitive impairment and SBP, DBP, PP, and MAP. The cutpoints at which risk for cognitive impairment (MMSE <24) was minimized were determined by quadratic models as 141 mm Hg, 85 mm Hg, 62 mm Hg, and 103 mm Hg, respectively. In the logistic models, U-shaped associations remained for SBP, DBP, and MAP but not PP. Below the identified cutpoints, each 1-mm Hg decrease in blood pressure corresponded to 0.7%, 1.1%, and 1.1% greater risk in the risk of cognitive impairment, respectively. Above the cutpoints, each 1-mm Hg increase in blood pressure corresponded to 1.2%, 1.8%, and 2.1% greater risk of cognitive impairment for SBP, DBP, and MAP, respectively.Conclusion
A U-shaped association between blood pressure and cognitive function in an elderly Chinese population was found. Recognition of these instances is important in identifying the high-risk population for cognitive impairment and to individualize blood pressure management for cognitive impairment prevention.