Wade Copeland

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants 1 124 897 men and women (mean age 53.4 years at baseline). Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Enterolignan Producing Phenotypes are Associated with Increased Gut Microbial Diversity and Altered Composition in Premenopausal Women in the United States

Background: Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure. Methods: We evaluated the association between the GMC in stool, urinary enterolignan excretion, and diet from a 3-day food record in 115 premenopausal (ages 40–45 years) women in the United States. Urinary enterolignans were measured using gas chromatography–mass spectroscopy. The GMC was evaluated using 454 pyrosequencing of the 16S rRNA gene. Sequences were aligned in SILVA (www.arb-silva.de). Operational taxonomic units were identified at 97% sequence similarity. Taxonomic classification was performed and alpha and beta diversity in relationship to ENL production were assessed. Multivariate analysis and regression were used to model the association between enterolignan excretion and the GMC. Bacteria associated with ENL production were identified using univariate analysis and ridge regression. Results: After adjusting for dietary fiber intake and adiposity, we found a significant positive association between ENL excretion and either the GMC (P = 0.0007), or the diversity of the GMC (P = 0.01). The GMC associated with high ENL production was distinct (UNIFRAC, P < 0.003, MRPP) and enriched in Moryella spp., Acetanaerobacterium spp., Fastidiosipila spp., and Streptobacillus spp. Conclusion: Diversity and composition of the GMC are associated with increased human exposure to enterolignans. Impact: Differences in gut microbial diversity and composition explain variation in gut metabolic processes that affect environmental exposures and influence human health. Cancer Epidemiol Biomarkers Prev; 24(3); 546–54. ©2014 AACR.

Characterisation of Familial Colorectal Cancer Type X, Lynch syndrome, and non-familial colorectal cancer

Background:Familial Colorectal Cancer Type X (FCCTX) is defined as individuals with colorectal cancer (CRC) who families meet Amsterdam Criteria-1 (AC1), but whose tumours are DNA-mismatch-repair-proficient, unlike Lynch syndrome (LS). FCCTX does not have an increased risk of extra-colonic cancers. This analysis compares epidemiologic and clinicopathologic features among FCCTX, LS, and ‘non-familial’ (non-AC1) CRC cases.Methods:From the Colon Cancer Family Registry, FCCTX (n=173), LS (n=303), and non-AC1 (n=9603) CRC cases were identified. Questionnaire-based epidemiologic information and CRC pathologic features were compared across case groups using polytomous logistic regression.Results:Compared with LS, FCCTX cases were less likely to be current (vs never) smokers; have a proximal subsite (vs rectal) tumour; or have mucinous histology, poor differentiation, or tumour-infiltrating lymphocytes. There were no observed differences in co-morbidities or medication usage.Conclusions:FCCTX were less likely to be current tobacco users; other exposures were similar between these groups. Histopathologic differences highly suggestive of LS CRCs do not appear to be shared by FCCTX.

Single-arm trial of the second version of an acceptance & commitment therapy smartphone application for smoking cessation

BACKGROUND The first randomized trial of a smartphone application (app) for adult smoking cessation (SmartQuit 1.0) revealed key features that predict cessation. These findings guided the revision of this Acceptance & Commitment Therapy (ACT)-based application (SmartQuit 2.0), which was primarily tested to examine participant receptivity, short-term cessation and reduction, and the relationship between program completion, smoking cessation and reduction. Secondarily, outcomes were descriptively compared with the SmartQuit1.0 trial. METHOD Adult participants (78% female, 25% with high school or less education, 30% unemployed) were recruited into the single-arm pilot trial (N=99) of SmartQuit 2.0 with a two-month follow-up (85% retention). RESULTS Regarding receptivity, 84% of participants were satisfied with SmartQuit 2.0 (vs. 59% for SmartQuit1.0), 73% would recommend it to a friend (vs. 48% for SmartQuit1.0), 81% found the ACT exercises useful for quitting (vs. 44% for SmartQuit1.0). At the 2-month follow-up, the quit rates were 21% for 7-day point prevalence (vs. 23% for SmartQuit1.0), 11% for 30-day point prevalence (vs. 13% for SmartQuit1.0), and 75% of participants reduced their smoking frequency (vs. 57% for SmartQuit1.0). Among program completers (24% of total sample), the quit rates were 33% for 7-day point prevalence, 28% for 30-day point prevalence, and 88% of participants reduced their smoking frequency. CONCLUSIONS The revised app had high user receptivity, modest quit rates, and high smoking reduction rates. Program completion may be key to boosting the apps effectiveness.

Increasing Cervical Cancer Screening in the United States‐Mexico Border Region

PURPOSE Hispanic women living on the United States-México border experience health disparities, are less likely to access cervical cancer screening services, and have a higher rate of cervical cancer incidence compared to women living in nonborder areas. Here we investigate the effects of an intervention delivered by community health workers (CHWs, known as lay health educators or Promotores de Salud in Spanish) on rates of cervical cancer screening in Hispanic women who were out of compliance with recommended screening guidelines. METHODS Hispanic women out of compliance with screening guidelines, attending clinics in southern New Mexico, were identified using medical record review. All eligible women were offered the intervention. The study was conducted between 2009 and 2011, and data were analyzed in 2012. Setting/participants--162 Hispanic women, resident in New Mexico border counties, aged 29-80 years, who had not had a Pap test within the past 3 years. Intervention--a CHW-led, culturally appropriate, computerized education intervention. Main outcome measures--the percentage of women who underwent cervical cancer screening within 12 months of receiving the intervention. Change in knowledge of, and attitudes toward cervical cancer and screening as assessed by a baseline and follow-up questionnaire. RESULTS 76.5% of women had a Pap test after the intervention. Women displayed increased knowledge about cervical cancer screening and about HPV. CONCLUSIONS A culturally appropriate promotora-led intervention is successful in increasing cervical cancer screening in at-risk Hispanic women on the United States-México border.

Get with the program: Adherence to a smartphone app for smoking cessation

INTRODUCTION Although engagement is generally predictive of positive outcomes in technology-based behavioral change interventions, engagement measures remain largely atheoretical and lack treatment-specificity. This study examines the extent to which adherence measures based on the underlying behavioral change theory of an Acceptance and Commitment Therapy (ACT) app for smoking cessation predict smoking outcomes, and user characteristics associated with adherence. METHODS Study sample was adult daily smokers in a single arm pilot study (n=84). Using the apps log file data, we examined measures of adherence to four key components of the ACT behavior change model as predictors of smoking cessation and reduction. We also examined baseline user characteristics associated with adherence measures that predict smoking cessation. RESULTS Fully adherent users (24%) were over four times more likely to quit smoking (OR=4.45; 95% CI=1.13, 17.45; p=0.032). Both an increase in tracking the number of urges passed (OR=1.02; 95% CI=1.00, 1.03; p=0.043) and ACT modules completed (OR=1.27; 95% CI=1.01, 1.60; p=0.042) predicted cessation. Lower baseline acceptance of cravings was associated with over four times higher odds of full adherence (OR=4.59; 95% CI=1.35, 15.54; p=0.014). CONCLUSIONS Full adherence and use of specific ACT theory-based components of the app predicted quitting. Consistent with ACT theory, users with low acceptance were most likely to adhere to the app. Further research is needed on ways to promote app engagement.

Kernel-penalized regression for analysis of microbiome data

The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.

Diabetes prevention in Hispanics: report from a randomized controlled trial.

Introduction Hispanics are at increased risk of developing type 2 diabetes. Lifestyle interventions are effective in preventing diabetes and restoring glucose regulation. Methods We recruited Hispanic men and women (N = 320) who were residents of the Lower Yakima Valley, Washington, aged 18 years or older with hemoglobin A1c (HbA1c) levels higher than 6% to a parallel 2-arm randomized-controlled trial conducted from 2008 through 2012. The trial compared participants in the intervention arm, who received an immediate educational curriculum (n = 166), to participants in the control arm, who received a delayed educational curriculum (n = 154). The home-based curriculum consisted of 5 sessions led by community health workers and was designed to inform participants about diabetes, diabetes treatment, and healthy dietary and physical activity behaviors. Participants were randomly assigned to the intervention and control arms, and analysts were blinded as to participant arm. We evaluated intervention effects on HbA1c levels; frequency (times per week) of fruit and vegetable consumption; and frequency (times per week) of mild, moderate, and strenuous leisure-time physical activity. At baseline, 3 months, and 6 months after randomization, participants completed a questionnaire and provided a blood sample. Analysts were blinded to intervention arm. Results The immediate intervention group (−0.64% [standard error (SE) 0.10]) showed a significant improvement in HbA1c scores (–37.5%, P = .04) compared with the delayed intervention group (–0.44%, P = .14). No significant changes were seen for dietary end points or changes in physical activity. We did observe a trend of greater increases in frequency of moderate and vigorous physical activity and a smaller increase in mild physical activity in the immediate intervention group than in the delayed intervention group. Conclusion This home-based intervention delivered by CHWs was associated with a clinically and statistically significant reduction in HbA1c levels in Hispanic adults with HbA1c levels higher than 6%.

Enhancing Biospecimen Knowledge Among Health Care Providers and Representatives From Community Organizations

In a personalized medicine environment, it is necessary to have access to a range of biospecimens to establish optimal plans for disease diagnosis and treatment for individual patients. Cancer research is especially dependent on biospecimens for determining ideal personalized treatment for patients. Unfortunately, the vast majority of biospecimens are collected from non-Hispanic White individuals; thus, minority representation is lacking. This has negative implications for comprehensive cancer treatment. The Geographic Management of Cancer Health Disparities Program (GMaP) Region 6 implemented a series of biospecimen education seminars adapted from the Biospecimen and Biobanking module of an existing Cancer Education and Training Program. Regional GMaP partners participated in a train-the-trainer webinar to familiarize themselves with the training materials. Participants trained by the trainers completed pre- and posttests to document changes in awareness, knowledge, and intention. Nine biospecimen education seminars were offered in 2013; 255 health care professionals and representatives from community organizations attended. Participants demonstrated a significant increase in knowledge, intention to donate samples, and intention to talk to patients about biospecimen sample donation. Representatives from community organizations had more improvement on knowledge scores than health care providers. Participation in a well-designed biospecimen education program may ameliorate some of the distrust of biomedical research experienced by racial/ethnic minorities and, in turn, increase needed minority representation in biospecimen collection.

Nightshift work, chronotype, and genome-wide DNA methylation in blood

ABSTRACT Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers. Methylation data were generated using the Illumina Infinium HumanMethylation450 BeadChip (450K) Array. After applying the latest methylation data processing methods, we compared methylation levels at 361,210 CpG loci between the groups using linear regression models adjusted for potential confounders and applied the false-discovery rate (FDR) ≤ 0.05 to account for multiple comparisons. No statistically significant associations at the genome-wide level were observed with shift work or chronotype, though based on raw P values and absolute effect sizes, there were suggestive associations in genes that have been previously linked with cancer (e.g., BACH2, JRK, RPS6KA2) and type-2 diabetes (e.g., KCNQ1). Given that our study was underpowered to detect moderate effects, examining these suggestive results in well-powered independent studies or in pooled data sets may improve our understanding of the pathways underlying the negative health effects of shift work and the influence of personal factors such as chronotype. Such an approach may help identify potential interventions that can be used to protect the long-term health of shift workers.