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Monteiro-Soares M.,Centro Hospitalar Of Vila Nova Of Gaia Espinho Epe | Boyko E.J.,Seattle Epidemiologic Research and Information Center | Boyko E.J.,University of Washington | Ribeiro I.,Matosinhos Local Health Unit Atlantida Extension
Diabetologia | Year: 2011

Aims/hypothesis: Several risk stratification systems have been proposed for predicting development of diabetic foot ulcer. However, little has been published that assesses their similarities and disparities, diagnostic accuracy and evidence level. Consequently, we conducted a systematic review of the existing stratification systems. Methods: We searched the MEDLINE database for studies (published until April 2010) describing the creation and validation of risk stratification systems for prediction of diabetic foot ulcer development. Results: We included 13 studies describing or evaluating the following different risk degree stratification systems: University of Texas; International Working Group on Diabetic Foot; Scottish Intercollegiate Guideline Network (SIGN); American Diabetes Association; and Boyko and colleagues. We confirmed that five variables were included in almost all the systems: diabetic neuropathy, peripheral vascular disease, foot deformity, and previous foot ulcer and amputation. The number of variables included ranged from four to eight and the number of risk groups from two to six. Only four studies reported or allowed the calculation of diagnostic accuracy measures. The SIGN system showed some higher diagnostic accuracy values, particularly positive likelihood ratio, while predictive ability was confirmed through external validation only in the system of Boyko et al. Conclusions/interpretation: Foot ulcer risk stratification systems are a much needed tool for screening patients with diabetes. The core variables of various systems are very similar, but the number of included variables in each model and risk groups varied greatly. Overall, the quality of evidence for these systems is low, as little validation of their predictive ability has been done. © 2011 Springer-Verlag.


LeardMann C.A.,Naval Health Research Center | Powell T.M.,Naval Health Research Center | Smith T.C.,Naval Health Research Center | Smith T.C.,University of San Diego | And 8 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

IMPORTANCE: Beginning in 2005, the incidence of suicide deaths in the US military began to sharply increase. Unique stressors, such as combat deployments, have been assumed to underlie the increasing incidence. Previous military suicide studies, however, have relied on case series and cross-sectional investigations and have not linked data during service with postservice periods. OBJECTIVE: To prospectively identify and quantify risk factors associated with suicide in current and former US military personnel including demographic, military, mental health, behavioral, and deployment characteristics. DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal study with accrual and assessment of participants in 2001, 2004, and 2007. Questionnaire data were linked with the National Death Index and the Department of Defense Medical Mortality Registry through December 31, 2008. Participants were current and former US military personnel from all service branches, including active and Reserve/National Guard, who were included in the Millennium Cohort Study (N = 151 560). MAIN OUTCOMES AND MEASURES: Death by suicide captured by the National Death Index and the Department of Defense Medical Mortality Registry. RESULTS: Through the end of 2008, findings were 83 suicides in 707 493 person-years of follow-up (11.73/100 000 person-years [95% CI, 9.21-14.26]). In Cox models adjusted for age and sex, factors significantly associated with increased risk of suicide included male sex, depression, manic-depressive disorder, heavy or binge drinking, and alcohol-related problems. None of the deployment-related factors (combat experience, cumulative days deployed, or number of deployments) were associated with increased suicide risk in any of the models. In multivariable Cox models, individuals with increased risk for suicide were men (hazard ratio [HR], 2.14; 95% CI, 1.17-3.92; P = .01; attributable risk [AR], 3.5 cases/10 000 persons), and those with depression (HR, 1.96; 95% CI, 1.05-3.64; P = .03; AR, 6.9/10 000 persons), manic-depressive disorder (HR, 4.35; 95% CI, 1.56-12.09; P = .005; AR, 35.6/10 000 persons), or alcohol-related problems (HR, 2.56; 95% CI, 1.56-4.18; P <.001; AR, 7.7/10 000 persons). A nested, matched case-control analysis using 20:1 control participants per case confirmed these findings. CONCLUSIONS AND RELEVANCE: In this sample of current and former military personnel observed July 1, 2001-December 31, 2008, suicide risk was independently associated with male sex and mental disorders but not with military-specific variables. These findings may inform approaches to mitigating suicide risk in this population.


Littman A.J.,Seattle Epidemiologic Research and Information Center | Tang M.-T.,Fred Hutchinson Cancer Research Center | Rossing M.A.,Fred Hutchinson Cancer Research Center
Journal of Cancer Survivorship | Year: 2010

Introduction: Few longitudinal studies have examined physical activity (PA) levels in breast cancer survivors and how those levels change following cancer diagnosis and treatment. Methods: We conducted a longitudinal cohort study of 315 female residents of Washington State, aged 21-74 years, diagnosed with a first primary invasive breast cancer between 2002 and 2004, and identified by a population-based cancer registry. Recreational PA was assessed for the 2-year period before diagnosis and at three intervals after diagnosis (1-12, 13-18, and 19-30 months). We calculated average metabolic equivalent task (MET) hours/wk of total, low-, moderate-, and vigorous-intensity PA. Results: Mean PA levels decreased by 50% in the 12 months after diagnosis relative to before diagnosis (from 18.8 to 9.2 MET-hours/wk). At 19-30 months post-diagnosis, overall PA levels had increased from the low levels reported in the first year after diagnosis, but remained approximately 3 MET-hours/wk lower than before diagnosis. Reductions were limited to moderate- and vigorous-intensity activities. Declines in PA differed according to certain characteristics of the study population, with the greatest reductions observed in women <40 years at diagnosis and with a pre-diagnosis body mass index <25 kg/m2; these women were also more likely to report the greatest activity before diagnosis. Conclusions: These results, if replicated in other studies, suggest that effective intervention strategies to increase PA in breast cancer survivors may differ according to patient characteristics. Implications for cancer survivors: Younger, normal weight, and relatively active women may benefit most from interventions to minimize the decline in PA following diagnosis, while women who are older, overweight, and relatively inactive at diagnosis may benefit from interventions to increase long-term PA. © 2010 Springer Science+Business Media, LLC.


Boscarino J.A.,00 N Academy Avenue | Boscarino J.A.,Mount Sinai School of Medicine | Forsberg C.W.,Seattle Epidemiologic Research and Information Center | Goldberg J.,Seattle Epidemiologic Research and Information Center | Goldberg J.,University of Washington
Psychosomatic Medicine | Year: 2010

OBJECTIVES: To assess the association between posttraumatic stress disorder (PTSD) and rheumatoid arthritis (RA) and to determine if this was due to PTSD or confounding by environmental and genetic factors. METHODS: Data were obtained from 3143 twin pairs in the Vietnam Era Twin Registry, which included male twin pairs who served during the Vietnam War era (mean age, 40.6 years; standard deviation, 2.9). Measurements included a PTSD symptom scale, history of physician-diagnosed RA, sociodemographics, and health confounding factors. Co-twin control analytic methods used generalized estimating equation logistic regression to account for the paired twin data and to examine the association between PTSD symptoms and RA in all twins. Separate analyses were conducted within twin pairs. RESULTS: The prevalence of RA among this population was 1.9% (95% confidence interval, 1.6-2.3) and the mean PTSD symptom level was 25.5 (standard deviation, 9.6). PTSD symptoms were associated with an increased likelihood of adult RA even after adjustment for confounding (ptrend <.001). Among all twins, those in the highest PTSD symptom quartile were 3.8 times more likely (95% confidence interval, 2.1-6.1) to have RA compared with those in the lowest. These findings also persist when examined within twin pairs (ptrend <.022). CONCLUSIONS: PTSD symptoms were associated with adult RA onset. Even after adjustment for familial/genetic factors and other confounders, an association between PTSD symptoms and RA remained. This is one of the first studies to demonstrate a link between PTSD and RA onset among a community-based population sample, independent of familial and genetic factors. Copyright © 2010 by the American Psychosomatic Society.


Boyko E.J.,Seattle Epidemiologic Research and Information Center | Seelig A.D.,Naval Health Research Center | Jacobson I.G.,Naval Health Research Center | Hooper T.I.,Uniformed Services University of the Health Sciences | And 3 more authors.
Diabetes Care | Year: 2013

OBJECTIVE Research has suggested that a higher risk of type 2 diabetes associated with sleep characteristics exists. However, studies have not thoroughly assessed the potential confounding effects of mental health conditions associated with alterations in sleep. RESEARCH DESIGN ANDMETHODSdWe prospectively assessed the association between sleep characteristics and self-reported incident diabetes among Millennium Cohort Study participants prospectively followed over a 6-year time period. Surveys are administered approximately every 3 years and collect self-reported data on demographics, height, weight, lifestyle, features of military service, sleep, clinician-diagnosed diabetes, and mental health conditions assessed by the PRIME-MD Patient Health Questionnaire and the PTSD Checklist-Civilian Version. Statistical methods for longitudinal data were used for data analysis. RESULTSdWe studied 47,093 participants (mean 34.9 years of age; mean BMI 26.0 kg/m2; 25.6% female). During 6 years of follow-up, 871 incident diabetes cases occurred (annual incidence 3.6/1,000 person-years). In univariate analyses, incident diabetes was significantly more likely among participants with self-reported trouble sleeping, sleep duration ,6 h, and sleep apnea. Participants reporting incident diabetes were also significantly older, of nonwhite race, of higher BMI, less likely to have been deployed, and more likely to have reported baseline symptoms of panic, anxiety, posttraumatic stress disorder, and depression. After adjusting for covariates, trouble sleeping (odds ratio 1.21 [95% CI 1.03-1.42]) and sleep apnea (1.78 [1.39-2.28]) were significantly and independently related to incident diabetes. CONCLUSIONSdTrouble sleeping and sleep apnea predict diabetes risk independent of mental health conditions and other diabetes risk factors. © 2013 by the American Diabetes Association.


Crum-Cianflone N.F.,Naval Health Research Center | Bagnell M.E.,Naval Health Research Center | Schaller E.,Naval Health Research Center | Boyko E.J.,Seattle Epidemiologic Research and Information Center | And 5 more authors.
Circulation | Year: 2014

Background - : The recent conflicts in Iraq and Afghanistan have exposed thousands of service members to intense stress, and as a result, many have developed posttraumatic stress disorder (PTSD). The role of military deployment experiences and PTSD in coronary heart disease (CHD) is not well defined, especially in young US service members with recent combat exposure. Methods and Results - : We conducted a prospective cohort study to investigate the relationships between wartime experiences, PTSD, and CHD. Current and former US military personnel from all service branches participating in the Millennium Cohort Study during 2001 to 2008 (n=60 025) were evaluated for newly self-reported CHD. Electronic medical record review for International Classification of Diseases, Ninth Revision, Clinical Modification codes for CHD was conducted among a subpopulation of active duty members (n=23 794). Logistic regression models examined the associations between combat experiences and PTSD with CHD with adjustment for established CHD risk factors. A total of 627 participants (1.0%) newly reported CHD over an average of 5.6 years of follow-up. Deployers with combat experiences had an increased odds of newly reporting CHD (odds ratio, 1.63; 95% confidence interval, 1.11-2.40) and having a diagnosis code for new-onset CHD (odds ratio, 1.93; 95% confidence interval, 1.31-2.84) compared with noncombat deployers. Screening positive for PTSD symptoms was associated with self-reported CHD before but not after adjustment for depression and anxiety and was not associated with a new diagnosis code for CHD. CONCLUSIONS - : Combat deployments are associated with new-onset CHD among young US service members and veterans. Experiences of intense stress may increase the risk for CHD over a relatively short period among young adults. © 2014 American Heart Association, Inc.


Zhao J.,University of Oklahoma | Goldberg J.,Seattle Epidemiologic Research and Information Center | Goldberg J.,University of Washington | Bremner J.D.,Emory University | Vaccarino V.,Emory University
Diabetes | Year: 2012

Insulin resistance (IR), the hallmark of type 2 diabetes, may be under epigenetic control. This study examines the association between global DNA methylation and IR using 84 monozygotic twin pairs. IR was estimated using homeostasis model assessment (HOMA). Global DNA methylation of Alu repeats in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between global DNA methylation and IR was examined using generalized estimating equation (GEE) and within-twin pair analyses, adjusting for potential confounders. Results show that methylation levels at all four CpG sites were individually associated with IR by GEE (all false discovery rate-adjusted P values ≤0.026). A 10% increase in mean Alu methylation was associated with an increase of 4.55 units (95% CI 2.38-6.73) in HOMA. Intrapair difference in IR was significantly associated with intrapair difference in global methylation level. A 10% increase in the difference in mean Alu methylation was associated with an increase of 4.54 units (0.34-8.71; P = 0.036) in the difference in HOMA. Confirmation of the results by intrapair analyses suggests that genetic factors do not confound the association between global DNA methylation and IR. Exclusion of twins taking diabetes medication (n = 17) did not change our results. © 2012 by the American Diabetes Association.


Zhao J.,The University of Oklahoma Health Sciences Center | Goldberg J.,Seattle Epidemiologic Research and Information Center | Goldberg J.,University of Washington | Vaccarino V.,Emory University
International Journal of Obesity | Year: 2013

Objective:Epigenetic mechanisms are increasingly being recognized as an important factor for obesity. The serotonin transporter gene (SLC6A4) has a critical role in regulating food intake, body weight and energy balance. This study examines the potential association between SLC6A4 promoter methylation and obesity measures in a monozygotic (MZ) twin sample.Methods:We studied 84 MZ twin pairs drawn from the Vietnam Era Twin Registry. Obesity measures include body mass index (BMI), body weight, waist circumference (WC) and waist-hip ratio (WHR). The SLC6A4 promoter methylation profile in peripheral blood leukocytes was quantified by bisulfite pyrosequencing. The association between methylation variation and obesity parameters was examined by mixed-model regression and matched pair analysis, adjusting for age, smoking, alcohol consumption, physical activity and total daily energy intake. Multiple testing was controlled using the adjusted false discovery rate (q-value).Results:Mean methylation level was positively correlated with BMI (r=0.29; P=0.0002), body weight (r=0.31; P<0.0001) and WC (r=0.20; P=0.009), but not WHR. Intra-pair differences in mean methylation were significantly correlated with intra-pair differences in BMI, body weight and WC, but not WHR. On average, a 1% increase in mean methylation was associated with 0.33 kg m -2 increase in BMI (95% CI: 0.02-0.65; P=0.03), 1.16 kg increase in body weight (95% CI, 0.16-2.16; P=0.02) and 0.78 cm increase in WC (95% CI, 0.05-1.50; P=0.03) after controlling for potential confounders.Conclusions:SLC6A4 promoter hypermethylation is significantly associated with an increased prevalence of obesity within a MZ twin study. © 2013 Macmillan Publishers Limited. All rights reserved.


Koepsell T.D.,Seattle Epidemiologic Research and Information Center | Koepsell T.D.,University of Washington | Littman A.J.,Seattle Epidemiologic Research and Information Center | Littman A.J.,University of Washington | Forsberg C.W.,Seattle Epidemiologic Research and Information Center
Obesity | Year: 2012

Veterans comprise a large and growing segment of the US population. Results from national telephone surveys suggest higher prevalence of overweight among Veterans compared with demographically similar non-Veterans, based on self-reported height and weight. Using 1999-2008 data from the National Health and Nutrition Examination Survey (NHANES), we compared 3,768 Veterans and 21,974 non-Veterans on: (i) several measures of adiposity based on direct anthropometry; (ii) life-course of self-reported BMI; and (iii) behaviors related to weight loss or maintenance. Whether Veterans were more likely than demographically similar non-Veterans to be obese or overweight depended on the adiposity measure employed. On BMI, Veterans were about equally likely to be obese (30 kg/m 2), but more likely to be overweight (25-29.9kg/m 2) by both self-report and by direct measurement (significantly so only by self-report). On waist-stature ratio, a roughly similar pattern was observed. On waist circumference, Veterans tended to have larger values than demographically similar non-Veterans, with more Veterans in the largest two categories. But on dual-photon X-ray absorptiometry, Veterans were less likely to have 35% body fat than non-Veterans of similar age, gender, and race/ethnicity. Life-course trends in self-reported BMI suggested a possible burst of weight gain after military discharge. These results suggest that Veterans may, on average, have less excess body fat than non-Veteransa pattern not revealed by standard anthropometric measures. © 2011 The Obesity Society.


Wells T.S.,Naval Health Research Center | Horton J.L.,Naval Health Research Center | Leardmann C.A.,Naval Health Research Center | Jacobson I.G.,Naval Health Research Center | Boyko E.J.,Seattle Epidemiologic Research and Information Center
Journal of Affective Disorders | Year: 2013

Background: In light of increased concerns about suicide in the military, institutional review boards have mandated increased scrutiny of the final item on the depression screening tool, the PHQ-9, which asks about suicidal thoughts. Since real-time monitoring of all individual responses in most observational studies is not feasible, many investigators have adopted the PHQ-8, choosing to remove the ninth item. This study compares the performance of the PHQ-8 with the PHQ-9 in a population-based sample of military or nonmilitary subjects. Methods: The Millennium Cohort Study administers a self-reported questionnaire that includes the PHQ-9 at 3-year intervals to current and former U.S. military personnel. PHQ-9 responses of 143,705 Millennium Cohort members were investigated. Cross-sectional comparisons of the PHQ-9 and PHQ-8 and prospective analyses to detect a 5-unit change in these measures were performed. Results: Greater than substantial agreement was found between the PHQ-8 and 9 instruments (kappas, 0.966-0.974 depending on survey cycle). There was similarly high agreement between the PHQ-8 and 9 in detecting a 5-point increase (κ=0.987) or decrease (κ=0.984) in score. Limitations: One potential limitation of this study is that participants completed the PHQ-9, and PHQ-8 scores were extrapolated from the PHQ-9. In addition, the Millennium Cohort may not fully represent the U.S. military; though previous evaluations have shown the cohort to be a well-representative sample. Conclusions: Since excellent agreement was detected between the PHQ-8 and PHQ-9 instruments, the PHQ-8 would capture nearly all the same cases of depression as the PHQ-9 in populations similar to the one in this study. © 2012 Elsevier B.V.

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