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Gould M.K.,Kaiser Permanente | Wagner T.H.,VA Palo Alto Health Care System | Wagner T.H.,Health Economics Research Center | Schultz E.M.,Stanford University | And 6 more authors.
Chest | Year: 2014

Background: PET scanning has been shown in randomized trials to reduce the frequency of surgery without cure among patients with potentially resectable non-small cell lung cancer (NSCLC). We examined whether more frequent use of PET scanning at the facility level improves survival among patients with NSCLC in real-world practice. Methods: In this prospective cohort study of 622 US veterans with newly diagnosed NSCLC, we compared groups defined by the frequency of PET scan use measured at the facility level and categorized as low ( < 25%), medium (25%-60%), or high ( > 60%). Results: The median age of the sample was 69 years. Ninety-eight percent were men, 36% were Hispanic or nonwhite, and 54% had moderate or severe comorbidities. At low-, medium-, and high-use facilities, PET scan was performed in 13%, 40%, and 72% of patients, respectively ( P < .0001). Baseline characteristics were similar across groups, including clinical stage based on CT scanning. More frequent use of PET scanning was associated with more frequent invasive staging ( P < .001) and nonsignificant improvements in downstaging ( P = .13) and surgery without cure ( P = .12). After a median of 352 days of follow-up, 22% of the sample was still alive, including 22% at low- and medium-use facilities and 20% at high-use facilities. After adjustment and compared with patients at low-use facilities, the hazard of death was greater for patients at high-use facilities (adjusted hazard ratio [HR], 1.35; 95% CI, 1.05-1.74) but not different for patients at medium-use facilities (adjusted HR, 1.14; 95% CI, 0.88-1.46). Conclusions: In this study of veterans with NSCLC, markedly greater use of PET scanning at the facility level was associated with more frequent use of invasive staging and possible improvements in downstaging and surgery without cure, but greater use of PET scanning was not associated with better survival. © 2014 American College of Chest Physicians.


Connelly J.J.,University of Virginia | Cherepanova O.A.,University of Virginia | Karaoli T.,University of Virginia | Lillard T.S.,University of Virginia | And 7 more authors.
Human Molecular Genetics | Year: 2013

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmedor stochastic nature of hypomethylation, identifyingthesechanges is important in understanding vascular disease,asmaintenance ofacells' epigenetic profile is essential for maintaining cellularphenotype. Global hypomethylation of proliferating aorticSMCsandconcomitant decrease ofDNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by 'genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2'-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P 5 0.017, OR 5 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex disease. © The Author 2013.


PubMed | Durham Epidemiologic Research and Information Center and University of South Carolina
Type: Journal Article | Journal: American journal of preventive medicine | Year: 2014

Nationally, youth are generally not achieving 60 minutes of daily moderate-to-vigorous physical activity (MVPA). Studies suggest that rural adults are less active than their urban counterparts, although studies of children are equivocal.To compare objectively measured physical activity across the rural-urban continuum in a sample of fourth- to eighth-grade youth.In fall 2010, youth from 20 North Carolina counties wore an accelerometer a minimum of 4 monitored days (n=804, 54% female, 25% African American, 54% urban). In spring 2013, two random-effects regression models were estimated separately for boys and girls. Comparisons among minutes of MVPA/day continuous and binary (60 minutes vs <60 minutes MVPA/day) among rural, suburban, and urban children were made, controlling for race, monitor wear time, and grade.For boys, there were no differences in MVPA/day among urbanicity categories. However, a 4.2 minutes/day decrease in MVPA occurred with each increase in grade. For girls, rural girls accumulated 9.3 minutes MVPA/day and 8.0 minutes MVPA/day more than suburban and urban girls, respectively. A 3 minutes/day decrease in MVPA occurred with each increase in grade. Rural girls were 4.6 times and 2.8 times more likely to accumulate 60 minutes MVPA/day compared to suburban and urban girls, respectively. No interactions across all models were significant for boys or girls.The relationship between urbanicity and MVPA in youth appears to be more complex than previously envisioned. Rural residence appears to be supportive of MVPA in girls but not boys. Future research should consider urbanicity when investigating correlates/determinants of MVPA in youth.


McNeil R.B.,Durham Epidemiologic Research and Information Center | Thomas C.M.,Durham Epidemiologic Research and Information Center | Coughlin S.S.,Emory University | Hauser E.,Durham Epidemiologic Research and Information Center | And 8 more authors.
Environmental Health: A Global Access Science Source | Year: 2013

Over the past two decades, 12 large epidemiologic studies and 2 registries have focused on U.S. veterans of the 1990-1991 Gulf War Era. We conducted a review of these studies' research tools to identify existing gaps and overlaps of efforts to date, and to advance development of the next generation of Gulf War Era survey tools. Overall, we found that many of the studies used similar instruments. Questions regarding exposures were more similar across studies than other domains, while neurocognitive and psychological tools were the most variable. Many studies focused on self-reported survey results, with a range of validation practices. However, physical exams, biomedical assessments, and specimen storage were not common. This review suggests that while research may be able to pool data from past surveys, future surveys need to consider how their design can yield data comparable with previous surveys. Additionally, data that incorporate recent technologies in specimen and genetic analyses would greatly enhance such survey data. When combined with existing data on deployment-related exposures and post-deployment health conditions, longitudinal follow-up of existing studies within this collaborative framework could represent an important step toward improving the health of veterans. © 2013 McNeil et al; licensee BioMed Central Ltd.


Wu R.R.,VA Health System | Wu R.R.,Duke University | Orlando L.A.,Duke University | Himmel T.L.,Duke University | And 7 more authors.
BMC Family Practice | Year: 2013

Background: Family health history (FHH) is the single strongest predictor of disease risk and yet is significantly underutilized in primary care. We developed a patient facing FHH collection tool, MeTree©, that uses risk stratification to generate clinical decision support for breast cancer, colorectal cancer, ovarian cancer, hereditary cancer syndromes, and thrombosis. Here we present data on the experience of patients and providers after integration of MeTree© into 2 primary care practices. Methods. This was a Type 2 hybrid controlled implementation-effectiveness study in 3 community-based primary care clinics in Greensboro, NC. All non-adopted adult English speaking patients with upcoming routine appointments were invited. Patients were recruited from December 2009 to the present and followed for one year. Ease of integration of MeTree© into clinical practice at the two intervention clinics was evaluated through patient surveys after their appointment and at 3 months post-visit, and physician surveys 3 months after tool integration. Results: Total enrollment =1,184. Average time to complete MeTree© = 27 minutes. Patients found MeTree©: easy to use (93%), easy to understand (97%), useful (98%), raised awareness of disease risk (85%), and changed how they think about their health (86%). Of the 26% (N = 311) asking for assistance to complete the tool, age (65 sd 9.4 vs. 57 sd 11.8, p-value < 0.00) and large pedigree size (24.4 sd 9.81 vs. 22.2 sd 8.30, p-value < 0.00) were the only significant factors; 77% of those requiring assistance were over the age of 60. Providers (N = 14) found MeTree©: improved their practice (86%), improved their understanding of FHH (64%), made practice easier (79%), and worthy of recommending to their peers (93%). Conclusions: Our study shows that MeTree © has broad acceptance and support from both patients and providers and can be implemented without disruption to workflow. © 2013 Wu et al.; licensee BioMed Central Ltd.


Wagner C.L.,University of Charleston | Hamilton S.A.,United Health Centers | McNeil R.,Durham Epidemiologic Research and Information Center | Hollis B.W.,University of Charleston | And 6 more authors.
International Journal of Endocrinology | Year: 2010

Objective: Determine prevalence of vitamin D deficiency (VDD) in a diverse group of women presenting for obstetrical care at two community health centers in South Carolina at latitude 32°N. Methods and Design: Any pregnant woman presenting for care at 2 community health centers was eligible to participate. Sociodemographic and clinical history were recorded. A single blood sample was taken to measure circulating 25(OH)D as indicator of vitamin D status [25(OH)D ≥ 20ng/mL (50nmol/L deficiency; 32ng/mL (80nmol/L) insufficiency]. Total serum calcium, phosphorus, creatinine, and intact parathyroid hormone also were measured. Results: 559 women, [mean age 25.0 ± 5.4 (range 1443) years] participated: African American (48%), Hispanic (38%), Caucasian/Other (14%). Mean gestational age was 18.5 ± 8.4 (median 14.6, range 6.439.6) weeks' gestation. 48% were VDD; an additional 37% insufficient. Greatest degree was in the African American women (68% deficient; 94% insufficient). In multivariable regression, 25(OH)D retained a significant negative association with PTH (P ≥ .001). Conclusions: VDD was high in a diverse group of women, greatest in those of darker pigmentation. The negative correlation between 25(OH)D and PTH confirms their corroborative use as biomarkers of VDD. These findings raise the issue of adequacy of current vitamin D recommendations for pregnant women. Copyright 2010 Stuart A. Hamilton et al.


Coughlin S.S.,Emory University | McNeil R.B.,Durham Epidemiologic Research and Information Center | Provenzale D.T.,Durham Epidemiologic Research and Information Center | Provenzale D.T.,Duke University | And 2 more authors.
Journal of Military and Veterans' Health | Year: 2013

Symptom-based conditions such as chronic fatigue syndrome (CFS) and medically unexplained multi-symptom illness (MSI) are fairly common in the general population and are also important veteran's health concerns due to their higher frequency among U.S. veterans who served during the 1990-1991 Gulf War. CFS, MSI, and other symptom-based conditions are often associated with considerable morbidity due to fatigue, chronic pain, neurologic symptoms, and other symptoms that can impair the quality of life. This article discusses several important issues of methodology that arise in population studies of CFS and MSI. These include the exclusion criteria that have been used in population studies to define CFS-like illness and unexplained MSI, the potential for false positive and false negative assessments of illness status, the potential for sex differences, and the poorly understood natural history of these symptom-based conditions across the life span. As an empirical example of these methodology issues, we examined existing data from a 2005 follow-up survey. We found that 64.9% (762 of 1,175) of female Gulf War veterans and 53.4% (2,530 of 4,739) of male Gulf War veterans had 1 or more exclusionary medical conditions. The prevalence among veterans with one or more exclusionary medical conditions increased markedly by age among females and those with a low Income.


Dungan J.R.,Duke University | Hauser E.R.,Duke University | Hauser E.R.,Durham Epidemiologic Research and Information Center | Qin X.,Duke University | Kraus W.E.,Duke University
Frontiers in Genetics | Year: 2013

Survivorship is a trait characterized by endurance and virility in the face of hardship. It is largely considered a psychosocial attribute developed during fatal conditions, rather than a biological trait for robustness in the context of complex, age-dependent diseases like coronary artery disease (CAD). The purpose of this paper is to present the novel phenotype, survivorship in CAD as an observed survival advantage concurrent with clinically significant CAD. We present a model for characterizing survivorship in CAD and its relationships with overlapping time- and clinically-related phenotypes. We offer an optimal measurement interval for investigating survivorship in CAD. We hypothesize genetic contributions to this construct and review the literature for evidence of genetic contribution to overlapping phenotypes in support of our hypothesis. We also present preliminary evidence of genetic effects on survival in people with clinically significant CAD from a primary case-control study of symptomatic coronary disease. Identifying gene variants that confer improved survival in the context of clinically appreciable CAD may improve our understanding of cardioprotective mechanisms acting at the gene level and potentially impact patients clinically in the future. Further, characterizing other survival-variant genetic effects may improve signal-to-noise ratio in detecting gene associations for CAD. © 2013 Dungan, Hauser, Qin and Kraus.


Singh A.,Duke University | Babyak M.A.,Duke University | Nolan D.K.,Duke University | Brummett B.H.,Duke University | And 7 more authors.
European Journal of Human Genetics | Year: 2015

We performed gene-environment interaction genome-wide association analysis (G × E GWAS) to identify SNPs whose effects on metabolic traits are modified by chronic psychosocial stress in the Multi-Ethnic Study of Atherosclerosis (MESA). In Whites, the G × E GWAS for hip circumference identified five SNPs within the Early B-cell Factor 1 (EBF1) gene, all of which were in strong linkage disequilibrium. The gene-by-stress interaction (SNP × STRESS) term P-values were genome-wide significant (Ps=7.14E-09 to 2.33E-08, uncorrected; Ps=1.99E-07 to 5.18E-07, corrected for genomic control). The SNP-only (without interaction) model P-values (Ps=0.011-0.022) were not significant at the conventional genome-wide significance level. Further analysis of related phenotypes identified gene-by-stress interaction effects for waist circumference, body mass index (BMI), fasting glucose, type II diabetes status, and common carotid intimal-medial thickness (CCIMT), supporting a proposed model of gene-by-stress interaction that connects cardiovascular disease (CVD) risk factor endophenotypes such as central obesity and increased blood glucose or diabetes to CVD itself. Structural equation path analysis suggested that the path from chronic psychosocial stress to CCIMT via hip circumference and fasting glucose was larger (estimate=0.26, P=0.033, 95% CI=0.02-0.49) in the EBF1 rs4704963 CT/CC genotypes group than the same path in the TT group (estimate=0.004, P=0.34, 95% CI=-0.004-0.012). We replicated the association of the EBF1 SNPs and hip circumference in the Framingham Offspring Cohort (gene-by-stress term P-values=0.007-0.012) as well as identified similar path relationships. This observed and replicated interaction between psychosocial stress and variation in the EBF1 gene may provide a biological hypothesis for the complex relationship between psychosocial stress, central obesity, diabetes, and cardiovascular disease. © 2015 Macmillan Publishers Limited. All rights reserved.

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