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Introduction: Implementation science (IS) offers methods to systematically achieve the Ending the HIV Epidemic goals in the United States, as well as the global UNAIDS targets. Federal funders such as the National Institutes of Mental Health (NIMH) have invested in implementation research to achieve these goals, including supporting the AIDS Research Centres (ARCs), which focus on high‐impact science in HIV and mental health (MH). To facilitate capacity building for the HIV/MH research workforce in IS, "grey areas," or areas of IS that are confusing, particularly for new investigators, should be addressed in the context of HIV/MH research. Discussion: A group of IS experts affiliated with NIMH‐funded ARCs convened to identify common and challenging grey areas. The group generated a preliminary list of 19 grey areas in HIV/MH‐related IS. From the list, the authors developed a survey which was distributed to all ARCs to prioritize grey areas to address in this paper. ARC members across the United States (N = 60) identified priority grey areas requiring clarification. This commentary discusses topics with 40% or more endorsement. The top grey areas that ARC members identified were: (1) Differentiating implementation strategies from interventions; (2) Determining when an intervention has sufficient evidence for adaptation; (3) Integrating recipient perspectives into HIV/MH implementation research; (4) Evaluating whether an implementation strategy is evidence‐based; (5) Identifying rigorous approaches for evaluating the impact of implementation strategies in the absence of a control group or randomization; and (6) Addressing innovation in HIV/MH IS grants. The commentary addresses each grey area by drawing from the existing literature (when available), providing expert guidance on addressing each in the context of HIV/MH research, and providing domestic and global HIV and HIV/MH case examples that address these grey areas. Conclusions: HIV/MH IS is key to achieving domestic and international goals for ending HIV transmission and mitigating its impact. Guidance offered in this paper can help to overcome challenges to rigorous and high‐impact HIV/MH implementation research. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent evidence suggests that higher levels of residential greenness may contribute to better mental health. Despite this, few studies have considered its impact on depression, and most are cross-sectional. OBJECTIVE: The objective of this study was to examine surrounding residential greenness and depression risk prospectively in the Nurses' Health Study. METHODS: A total of 38,947 women (mean age throughout follow-up 70 y [range 54-91 y]) without depression in 2000 were followed to 2010. Residential greenness was measured using the satellite-based Normalized Difference Vegetation Index (NDVI) and defined as the mean greenness value within [Formula: see text] and [Formula: see text] radii of the women's residences in July of each year. Incidence of depression was defined according to the first self-report of either physician-diagnosed depression or regular antidepressant use. We used Cox proportional hazards models to examine the relationship between greenness and depression incidence and assessed physical activity as a potential effect modifier and mediator. RESULTS: Over 315,548 person-years, 3,612 incident depression cases occurred. In multivariable-adjusted models, living in the highest quintile of residential greenness within [Formula: see text] was associated with a 13% reduction in depression risk ([Formula: see text] [95% confidence interval (CI): 0.78, 0.98]) compared with the lowest quintile. The association between greenness and depression did not appear to be mediated by physical activity, nor was there evidence of effect modification by physical activity. CONCLUSIONS: In this population of mostly white women, we estimated an inverse association between the highest level of surrounding summer greenness and the risk of self-reported depression. [ABSTRACT FROM AUTHOR]

Implementation trials often involve clustering via risk networks, where only some participants directly receive the intervention. The individual effect is that among directly treated persons beyond being in an intervention network; the disseminated effect is that among persons engaged with those directly treated. In this article, we employ a causal inference framework and discuss assumptions and estimators for individual and disseminated effects and apply them to the HIV Prevention Trials Network 037 Study. HIV Prevention Trials Network 037 was a phase III, network-level, randomized controlled human immunodeficiency virus (HIV) prevention trial conducted in the United States and Thailand from 2002 to 2006 that recruited injection drug users, who were assigned to either an intervention group or a control group, and their risk network members, who received no direct intervention. Combining individual and disseminated effects, we observed a 35% composite rate reduction in the adjusted model (risk ratio = 0.65, 95% confidence interval: 0.47, 0.90). Methodology is now available for estimating the full set of these effects, enhancing knowledge gained from network-randomized trials. Although the overall effect gains validity from network randomization, we show that it will generally be less than the composite effect. Additionally, if only index participants benefit from the intervention, as the network size increases, the overall effect tends toward the null—an unfortunate and misleading conclusion. [ABSTRACT FROM AUTHOR]

We evaluated the performance of a semiquantitative food frequency questionnaire (SFFQ), the Automated Self-Administered 24-Hour Dietary Recall (ASA24), and 7-day dietary records (7DDRs), in comparison with biomarkers, in the estimation of nutrient intakes among 627 women in the Women's Lifestyle Validation Study (United States, 2010-2012). Two paper SFFQs, 1 Web-based SFFQ, 4 ASA24s (beta version), 2 7DDRs, 4 24-hour urine samples, 1 doubly labeled water measurement (repeated among 76 participants), and 2 fasting blood samples were collected over a 15-month period. The dietary variables evaluated were energy, energy-adjusted intakes of protein, sodium, potassium, and specific fatty acids, carotenoids, a-tocopherol, retinol, and folate. In general, relative to biomarkers, averaged ASA24s had lower validity than the SFFQ completed at the end of the data-collection year (SFFQ2); SFFQ2 had slightly lower validity than 1 7DDR; the averaged SFFQs had validity similar to that of 1 7DDR; and the averaged 7DDRs had the highest validity. The deattenuated correlation of energy-adjusted protein intake assessed by SFFQ2 with its biomarker was 0.46, similar to its correlation with 7DDRs (deattenuated r = 0.54). These data indicate that the SFFQ2 provides reasonably valid measurements of energy-adjusted intake for most of the nutrients assessed in our study, consistent with earlier conclusions derived using 7DDRs as the comparison method. The ASA24 needs further evaluation for use in large population studies, but an average of 3 days of measurement will not be sufficient for some important nutrients. [ABSTRACT FROM AUTHOR]

The authors evaluated the validity of a 152-item semiquantitative food frequency questionnaire (SFFQ) by comparing it with two 7-day dietary records (7DDRs) or up to 4 automated self-administered 24-hour recalls (ASA24s) over a 1-year period in the women's Lifestyle Validation Study (2010-2012), conducted among subgroups of the Nurses' Health Studies. Intakes of energy and 44 nutrients were assessed using the 3 methods among 632 US women. Compared with the 7DDRs, SFFQ responses tended to underestimate sodium intake but overestimate intakes of energy, macronutrients, and several nutrients in fruits and vegetables, such as carotenoids. Spearman correlation coefficients between energy-adjusted intakes from 7DDRs and the SFFQ completed at the end of the data-collection period ranged from 0.36 for lauric acid to 0.77 for alcohol (mean r = 0.53). Correlations of the end-period SFFQ were weaker when ASA24s were used as the comparison method (mean r = 0.43). After adjustment for within-person variation in the comparison method, the correlations of the final SFFQ were similar with 7DDRs (mean r = 0.63) and ASA24s (mean r = 0.62). These data indicate that this SFFQ provided reasonably valid estimates for intakes of a wide variety of dietary variables and that use of multiple 24-hour recalls or 7DDRs as a comparison method provided similar conclusions if day-to-day variation was taken into account. [ABSTRACT FROM AUTHOR]

We examined the proportions of multiple types of breast cancers in the population that were attributable to established risk factors, focusing on behaviors that are modifiable at menopause. We estimated the full and partial population attributable risk percentages (PAR%) by combining the relative risks and the observed prevalence rates of the risk factors of interest. A total of 8,421 cases of invasive breast cancer developed in postmenopausal women (n = 121,700) in the Nurses' Health Study from 1980-2010. We included the following modifiable risk factors in our analyses: weight change since age 18 years, alcohol consumption, physical activity level, breastfeeding, and menopausal hormone therapy use. Additionally, the following nonmodifiable factors were included: age, age at menarche, height, a combination of parity and age at first birth, body mass index at age 18 years, family history of breast cancer, and prior benign breast disease. When we considered all risk factors (and controlled for age), the PAR% for invasive breast cancers was 70.0% (95% confidence interval: 55.0, 80.7). When considering only modifiable factors, we found that changing the risk factor profile to the lowest weight gain, no alcohol consumption, high physical activity level, breastfeeding, and no menopausal hormone therapy use was associated with a PAR% of 34.6% (95% confidence interval: 22.7, 45.4). The PAR% for modifiable factors was higher for estrogen receptor-positive breast cancers (PAR% = 39.7%) than for estrogen receptor-negative breast cancers (PAR% = 27.9%). Risk factors that are modifiable at menopause account for more than one-third of postmenopausal breast cancers; therefore, a substantial proportion of breast cancer in the United States is preventable. [ABSTRACT FROM AUTHOR]

Background: Plant-based diets have been recommended to reduce the risk of type 2 diabetes (T2D). However, not all plant foods are necessarily beneficial. We examined the association of an overall plant-based diet and hypothesized healthful and unhealthful versions of a plant-based diet with T2D incidence in three prospective cohort studies in the US.Methods and Findings: We included 69,949 women from the Nurses' Health Study (1984-2012), 90,239 women from the Nurses' Health Study 2 (1991-2011), and 40,539 men from the Health Professionals Follow-Up Study (1986-2010), free of chronic diseases at baseline. Dietary data were collected every 2-4 y using a semi-quantitative food frequency questionnaire. Using these data, we created an overall plant-based diet index (PDI), where plant foods received positive scores, while animal foods (animal fats, dairy, eggs, fish/seafood, poultry/red meat, miscellaneous animal-based foods) received reverse scores. We also created a healthful plant-based diet index (hPDI), where healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, tea/coffee) received positive scores, while less healthy plant foods (fruit juices, sweetened beverages, refined grains, potatoes, sweets/desserts) and animal foods received reverse scores. Lastly, we created an unhealthful plant-based diet index (uPDI) by assigning positive scores to less healthy plant foods and reverse scores to healthy plant foods and animal foods. We documented 16,162 incident T2D cases during 4,102,369 person-years of follow-up. In pooled multivariable-adjusted analysis, both PDI and hPDI were inversely associated with T2D (PDI: hazard ratio [HR] for extreme deciles 0.51, 95% CI 0.47-0.55, p trend < 0.001; hPDI: HR for extreme deciles 0.55, 95% CI 0.51-0.59, p trend < 0.001). The association of T2D with PDI was considerably attenuated when we additionally adjusted for body mass index (BMI) categories (HR 0.80, 95% CI 0.74-0.87, p trend < 0.001), while that with hPDI remained largely unchanged (HR 0.66, 95% CI 0.61-0.72, p trend < 0.001). uPDI was positively associated with T2D even after BMI adjustment (HR for extreme deciles 1.16, 95% CI 1.08-1.25, p trend < 0.001). Limitations of the study include self-reported diet assessment, with the possibility of measurement error, and the potential for residual or unmeasured confounding given the observational nature of the study design.Conclusions: Our study suggests that plant-based diets, especially when rich in high-quality plant foods, are associated with substantially lower risk of developing T2D. This supports current recommendations to shift to diets rich in healthy plant foods, with lower intake of less healthy plant and animal foods. [ABSTRACT FROM AUTHOR]

Background: Although obesity has been linked to an increased risk of colorectal cancer (CRC), the risk associated with long-term status or change of body fat distribution has not been fully elucidated.Methods: Using repeated anthropometric assessments in the Nurses' Health Study and Health Professionals Follow-up Study, we prospectively investigated cumulative average waist circumference, hip circumference and waist-to-hip ratio, as well as their 10-year changes over adulthood, in relation to CRC risk over 23-24 years of follow-up. Cox proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI).Results: High waist circumference, hip circumference and waist-to-hip ratio were all associated with a higher CRC risk in men, even after adjusting for body mass index. The association was attenuated to null in women after adjusting for body mass index. Ten-year gain of waist circumference was positively associated with CRC risk in men (P for trend = 0.03), but not in women (P for trend = 0.34).Compared with men maintaining their waist circumference, those gaining waist circumference by ≥ 10 cm were at a higher risk of CRC, with a multivariable-adjusted HR of 1.59 (95% CI, 1.01-2.49). This association appeared to be independent of weight change.Conclusions: Abdominal adiposity, independent of overall obesity, is associated with an increased CRC risk in men but not in women. Our findings also provide the first prospective evidence that waist circumference gain during adulthood may be associated with higher CRC risk in men, thus highlighting the importance of maintaining a healthy waist for CRC prevention. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a prevalent gynecologic disease associated with systemic chronic inflammation, heightened oxidative stress, and atherogenic lipid profile that may increase women's risk for coronary heart disease (CHD).Methods and Results: We examined the prospective association between laparoscopically confirmed endometriosis and subsequent CHD among 116 430 women in the Nurses' Health Study II (1989-2009). Participants with a history of heart disease and stroke were excluded. When compared with women without endometriosis, women with laparoscopically confirmed endometriosis had a higher risk of myocardial infarction (relative risk, 1.52; 95% confidence interval, 1.17-1.98), angiographically confirmed angina (1.91; 1.59-2.29), coronary artery bypass graft surgery/coronary angioplasty procedure/stent (1.35; 1.08-1.69), or any of these CHD end points combined (1.62; 1.39-1.89), independent of potential demographic, anthropometric, family history, reproductive, and lifestyle confounders. Relative risk for the combined CHD end point was highest among women aged ≤40 years (3.08; 2.02-4.70) and decreased as age increased (40< age ≤50 years, 1.65; 1.35-2.02; 50< age ≤55 years, 1.44; 1.07-1.94; and age >55 years, 0.98; 0.56-1.72; P value, test for heterogeneity=0.001). Having had a hysterectomy/oophorectomy was associated with higher risk of combined CHD compared with not having had a hysterectomy/oophorectomy (1.51; 1.34-1.71). A percentage of 42 of the association between endometriosis and CHD could be explained by greater frequency of hysterectomy/oophorectomy and earlier age at surgery after endometriosis diagnosis.Conclusions: In this large, prospective cohort, laparoscopically confirmed endometriosis was associated with increased risk of CHD. The association was strongest among young women. Hysterectomy/oophorectomy was associated with higher risk of CHD and could partially explain the association between endometriosis and CHD. [ABSTRACT FROM AUTHOR]

Background: Prospective data on the relation of magnesium, potassium, and calcium intakes with stroke risk are inconsistent, and to our knowledge, the effect of a combined mineral diet score has not been examined. Objective: We examined associations between intakes of magnesium, potassium, and calcium and risk of incident stroke in 86,149 women in the Nurses' Health Study (NHS) I and 94,715 women in the NHS II. Design: In this prospective cohort study, we calculated HRs of stroke by quintiles of intake for each mineral and for a combined diet score of all 3 minerals by using multivariate Cox proportional hazard models. In addition, we updated meta-analyses on dietary intakes of these minerals and risk of stroke. Results: During follow-up (30 y in the NHS I; 22 y in the NHS II) a total of 3780 incident stroke cases were documented. Pooled multivariate RRs of total stroke for women in the highest compared with the lowest quintiles were 0.87 (95% CI: 0.78, 0.97) for total magnesium, 0.89 (95% CI: 0.80, 0.99) for total potassium, and 0.97 (95% CI: 0.87, 1.09) for total calcium intake. Pooled RRs for women in the highest compared with the lowest quintiles of a combined mineral diet score were 0.72 (95% CI: 0.65, 0.81) for total stroke, 0.78 (95% CI: 0.66, 0.92) for ischemic stroke, and 0.80 (95% CI: 0.61, 1.04) for hemorrhagic stroke. In the updated meta-analyses of all prospective studies to date, the combined RR of total stroke was 0.87 (95% CI: 0.83, 0.92) for a 100-mg/d increase in magnesium intake, 0.91 (95% CI: 0.88, 0.94) for a 1000-mg/d increase in potassium intake, and 0.98 (95% CI: 0.94, 1.02) for a 300-mg/d increase in calcium intake. Conclusions: A combined mineral diet score was inversely associated with risk of stroke. High intakes of magnesium and potassium but not calcium were also significantly associated with reduced risk of stroke in women. [ABSTRACT FROM AUTHOR]

Background: A body of literature has suggested an elevated risk of lung cancer associated with particulate matter and traffic-related pollutants. Objective: We examined the relation of lung cancer incidence with long-term residential exposures to ambient particulate matter and residential distance to roadway, as a proxy for traffic-related exposures. Methods: For participants in the Nurses’ Health Study, a nationwide prospective cohort of women, we estimated 72‑month average exposures to PM2.5, PM2.5–10, and PM10 and residential distance to road. Follow-up for incident cases of lung cancer occurred from 1994 through 2010. Cox proportional hazards models were adjusted for potential confounders. Effect modification by smoking status was examined. Results: During 1,510,027 person-years, 2,155 incident cases of lung cancer were observed among 103,650 participants. In fully adjusted models, a 10‑μg/m3 increase in 72‑month average PM10 [hazard ratio (HR) = 1.04; 95% CI: 0.95, 1.14], PM2.5 (HR = 1.06; 95% CI: 0.91, 1.25), or PM2.5-10 (HR = 1.05; 95% CI: 0.92, 1.20) was positively associated with lung cancer. When the cohort was restricted to never-smokers and to former smokers who had quit at least 10 years before, the associations appeared to increase and were strongest for PM2.5 (PM10: HR = 1.15; 95% CI: 1.00, 1.32; PM2.5: HR = 1.37; 95% CI: 1.06, 1.77; PM2.5-10: HR = 1.11; 95% CI: 0.90, 1.37). Results were most elevated when restricted to the most prevalent subtype, adenocarcinomas. Risks with roadway proximity were less consistent. Conclusions: Our findings support those from other studies indicating increased risk of incident lung cancer associated with ambient PM exposures, especially among never- and long-term former smokers. [ABSTRACT FROM AUTHOR]

Aspirin use decreases colon cancer risk, but this association may vary among population subgroups. The aspirin-colon cancer association was evaluated according to body mass index and physical activity in 1,701 incident colon cancer cases diagnosed during follow-up of 139,310 participants for up to 26 years in 2 US prospective cohort studies that began in 1980 and 1992, respectively. Whether plasma C-peptide levels modified the association was examined by using a nested case-control design (n = 384 cases, 749 controls). Multiplicative and additive interactions were tested. Body mass index did not modify the association; pooled multivariable relative risks for regular aspirin use versus nonuse ranged from 0.74 to 0.75 in the normal weight and obese groups (test for multiplicative interaction, P = 0.75; test for additive interaction, P = 0.66). Pooled multivariable relative risks for regular aspirin use were 0.86 (95% confidence interval (CI): 0.66, 1.11) in the low and 0.67 (95% CI: 0.58, 0.77) in the high physical activity groups with no interaction evident on either the multiplicative or additive scale (P > 0.10). Plasma C-peptide levels also did not modify the aspirin-colon cancer association, with multivariable relative risks of 0.74 (95% CI: 0.50, 1.10) for the low and 0.65 (95% CI: 0.46, 0.92) for the high group. Reductions in colon cancer risk associated with aspirin use were not significantly modified by body mass index, physical activity, or plasma C-peptide level in this study. [ABSTRACT FROM AUTHOR]

Background: Environmental exposure to polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) has been associated with the risk of non-Hodgkin lymphoma.Methods: We conducted a case-control study nested within the Physicians' Health Study, a prospective cohort established in 1982. We measured concentrations of PCBs and p,p'-DDE in baseline blood samples from 205 men later diagnosed with non-Hodgkin lymphoma and 409 age- and race-matched controls. Lipid-adjusted organochlorine concentrations were categorized into quintiles based on the distribution among controls. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for each quintile relative to the lowest quintile. We also evaluated these associations for major histologic subtypes of non-Hodgkin lymphoma.Results: The risk of non-Hodgkin lymphoma was positively associated with the sum of 51 PCB congeners assayed (SigmaPCB); the group of immunotoxic congeners; the individual congeners 118, 138, 153, and 180; and the sum of these 4 congeners. The simple OR for the highest quintile of lipid-adjusted SigmaPCB versus the lowest was 1.9 (95% CI = 1.1-3.2; test for trend, P = 0.001), with similar trends for individual congeners and groups defined as above. Adjustment for height, body mass index, alcohol intake, smoking, and fish intake did not substantially change the effect estimates. No association was observed for p,p'-DDE. There was no evidence of statistical heterogeneity in effects by histologic subtype of lymphoma; however, this analysis was underpowered.Conclusions: These results support the hypothesis of a positive association between PCB exposure and development of NHL in men. [ABSTRACT FROM AUTHOR]

Background: Although the smoking rate in the United States is declining because of an increase of smoke-free laws, among blue-collar workers it remains higher than that among many other occupational groups. Objectives: We evaluated the factors influencing workplace secondhand smoke (SHS) exposures in the U.S. unionized trucking industry. Method s: From 2003 through 2005, we measured workplace SHS exposure among 203 nonsmoking and 61 smoking workers in 25 trucking terminals. Workers in several job groups wore personal vapor-phase nicotine samplers on their lapels for two consecutive work shifts and completed a workplace SHS exposure questionnaire at the end of the personal sampling. Results: Median nicotine level was 0.87 μg/m³ for nonsmokers and 5.96 μg/m³ for smokers. As expected, smokers experienced higher SHS exposure duration and intensity than did nonsmokers. For nonsmokers, multiple regression analyses indicated that self-reported exposure duration combined with intensity, lack of a smoking policy as reported by workers, having a nondriver job, and lower educational level were independently associated with elevated personal nicotine levels (model R² = 0.52). Nondriver job and amount of active smoking were associated with elevated personal nicotine level in smokers, but self-reported exposure, lack of a smoking policy, and lower educational level were not. Conclusions: Despite movements toward smoke-free laws, this population of blue-collar workers was still exposed to workplace SHS as recently as 2005. The perceived (reported by the workers), rather than the official (reported by the terminal managers), smoking policy was associated with measured SHS exposure levels among the nonsmokers. Job duties and educational level might also be important predictors of workplace SHS exposure. [ABSTRACT FROM AUTHOR]

Background: A potential role of prenatal and perinatal exposures in autoimmunity has been hypothesized, but few studies have examined the relation between various prenatal and perinatal factors and the risk of multiple sclerosis (MS).Methods: The study population included participants in the Nurses' Health Studies--2 prospective cohorts that together comprise 238,381 female nurses, who self-reported exposure to prenatal and perinatal factors. In addition, 35,815 nurses' mothers participated by providing detailed information regarding experiences surrounding their daughter's birth. The following prenatal and perinatal factors were studied in relation to MS: fetal growth, birth season, preterm birth, mode of delivery, maternal weight gain, medical conditions, medication use, diethylstilbestrol exposure, prenatal health care, maternal activity level, maternal obstetric history, parental age, and prenatal and childhood passive smoke exposure.Results: The sample included 723 confirmed MS cases, including 383 with diagnosis after reporting prenatal and perinatal factors. Few associations were observed. These included an increased risk among women whose mothers reported late initiation of prenatal care (after the first trimester) (27 cases; rate ratio = 1.6 [95% confidence interval = 1.0-2.4]), diabetes during pregnancy (2 cases; 10 [2.5-42]), and maternal prepregnancy overweight/obesity (20 cases; 1.7 [1.0-2.7]). Results also suggested a possible increase in incident MS risk among women with prenatal diethylstilbestrol exposure (9 cases; 1.8 [0.93-3.5]).Conclusions: This study provides modest support for a role of prenatal factors in MS risk. The results should be interpreted cautiously due to the limited statistical power, potential for exposure misclassification, and possibility of chance findings. [ABSTRACT FROM AUTHOR]

Background: Uterine leiomyomata are a major source of morbidity in black women. We prospectively investigated the risk of self-reported uterine leiomyomata in relation to body mass index (BMI), weight change, height, waist and hip circumferences, and waist-to-hip ratio in a large cohort of U.S black women.Methods: Data were derived from the Black Women's Health Study, a U.S. prospective cohort study of black women who complete biannual mailed health questionnaires. From 1997 through 2001, we followed 21,506 premenopausal women with intact uteri and no prior diagnosis of uterine leiomyomata. Cox regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs).Results: After 70,345 person-years of follow up, 2146 new cases of uterine leiomyomata confirmed by ultrasound (n = 1885) or hysterectomy (n = 261) were self-reported. Compared with the thinnest women (BMI <20.0 kg/m), the multivariate IRRs for women with BMIs of 20.0-22.4, 22.5-24.9, 25.0-27.4, 27.5-29.9, 30.0-32.4, and 32.5+ kg/m were 1.34 (95% CI = 1.02-1.75), 1.39 (1.07-1.81), 1.45 (1.12-1.89), 1.47 (1.11-1.93), 1.36 (1.02-1.80), and 1.21 (0.93-1.58), respectively. IRRs were larger among parous women. Weight gain since age 18 was positively associated with risk, but only among parous women. No other anthropometric measures were associated with risk.Conclusions: BMI and weight gain exhibited a complex relation with risk of uterine leiomyomata in the Black Women's Health Study. The BMI association was inverse J-shaped and findings were stronger in parous women. Weight gain was positively associated with risk among parous women only. [ABSTRACT FROM AUTHOR]

Background: Although it is known that abdominal obesity increases the risk of chronic diseases, prospective data examining the relation between lifestyle factors and the accumulation of abdominal adipose tissue are sparse. Objective: The objective of the study was to determine the associations of changes in diet, physical activity, alcohol consumption, and smoking with 9-y waist gain among US men. Design: A prospective cohort comprised 16 587 US men aged 40-75 y at baseline in 1986. Data on lifestyle factors were provided periodically with the use of self-reported questionnaires, and participants measured and reported their waist circumference in 1987 and 1996. Results: In multivariate analyses, a 2% increment in energy intake from trans fats that were isocalorically substituted for either polyunsaturated fats or carbohydrates was significantly associated with a 0.77-cm waist gain over 9 y (P < 0.001 for each comparison). An increase of 12 g total fiber/d was associated with a 0.63-cm decrease in waist circumference (P < 0.001), whereas smoking cessation and a 20-h/wk increase in television watching were associated with a 1.98-cm and 0.59-cm waist gain, respectively (P < 0.001). Increases of 25 metabolic equivalent tasks (METs) · h/wk in vigorous physical activity and of = 0.5 h/wk in weight training were associated with 0.38-cm and 0.91-cm decreases in waist circumference, respectively (P < 0.001 for each comparison). These associations remained significant after further adjustment for concurrent change in body mass index. Changes in total fat and alcohol consumption and in walking volume were not significantly related to waist gain. Conclusions: Waist gain may be modulated by changes in trans fat and fiber consumption, smoking cessation, and physical activity. [ABSTRACT FROM AUTHOR]

Examines predictors of airborne endotoxin in Boston area homes. Distribution and correlation of airborne endotoxin with other measurements; Effect of season on airborne endotoxin level; Development of predictive models for airborne endotoxin level.

Data derived from laboratory investigations suggest that a number of dietary variables may contribute to bladder carcinogenesis. Although bladder cancer is the fourth leading cause of cancer in men in the United States, dietary studies are few. The authors examined the relations between intakes of macro- and micronutrients and the risk of bladder cancer among men in the prospective Health Professionals Follow-Up Study. Each participant completed a 131-item food frequency questionnaire in 1986 and in 1990, from which nutrient intakes were calculated. During 12 years of follow-up, 320 cases of bladder cancer were diagnosed. No association was observed for total caloric or macronutrient intake and bladder cancer risk. Similarly, we found no relation for dietary intake of potassium, sodium, calcium, magnesium, phosphorus, iron, or water-soluble vitamins and bladder cancer risk. Total vitamin E intake and vitamin E supplements were inversely associated with risk. In addition, a dose-response relation was observed for duration of vitamin E supplement use. A suggestive inverse association was seen with dose of vitamin C supplement use. More studies are needed to determine the role of vitamins E and C supplement intake in bladder carcinogenesis. [ABSTRACT FROM PUBLISHER]

Background: The Dietary Guidelines for Americans and the food guide pyramid aim to reduce the risk of major chronic disease in the United States, but data supporting their overall effectiveness are sparse. The healthy eating index (HEI) measures the concordance of dietary patterns with these guidelines. Objective:We tested whether a high HEI score (range: 0-100; 100 is best) calculated from a validated food-frequency questionnaire (HEI-f) could predict lower risk of major chronic disease in men. Design: A cohort of US male health professionals without major disease completed detailed questionnaires on food intake and other risk factors for heart disease and cancer in 1986 and repeatedly during the 8-y follow-up. Major chronic disease outcome was defined as incident major cardiovascular disease (stroke or myocardial infarction, n = 1092), cancer (n = 1661), or other non-trauma-related deaths (n = 366). Results: The HEI-f was weakly inversely associated with risk of major chronic disease [comparing highest with lowest quintile of the HEI-f, relative risk (RR) = 0.89; 95% CI: 0.79, 1.00; P < 0.001 for trend]. The HEI-f was associated with moderately lower risk of cardiovascular disease (RR = 0.72; 95% CI: 0.60, 0.88; P < 0.001) but was not associated with lower cancer risk. Conclusions: The HEI-f was only weakly associated with risk of major chronic disease, suggesting that improvements to the HEI may be warranted. Further research on the HEI could have implications for refinements to the Dietary Guidelines for Americans and the food guide pyramid. [ABSTRACT FROM AUTHOR]

Evaluates regional variation in breast cancer incidence rates in the Nurses' Health Study in the United States. Measurement of influence of breast cancer risk factors at the individual level; Comparison of premenopausal and postmenopausal women.

Menstrual cycle characteristics and ovulatory infertility were evaluated in relation to breast cancer risk among 116,678 women in the Nurses' Health Study II, a prospective cohort study of female registered nurses who were aged 25–42 years and living in 14 US states at enrollment in 1989. During 396,299 person-years of follow-up between return of the baseline questionnaire and June 1993, 251 cases of breast cancer were identified in this cohort. The multivariate relative risk (RR) associated with age at menarche >13 years compared with age ≤12 years was 0.66 (95% confidence interval (CI) 0.44–0.99). Short and long menstrual cycle lengths at ages 18–22 years were associated with reduced risk. Compared with menstrual cycle length 26–31 days, the multivariate relative risks (95% CIs) for more extreme cycle lengths were: <26 days, 0.50 (0.25–0.98); 32–39 days, 0.81 (0.51–1.28); and >39 days or too irregular for estimation of a usual cycle length, 0.41 (0.18–0.94). The multivariate relative risk associated with a history of ovulatory infertility, compared with no such history, was 0.41 (95% CI 0.18–0.93). These results are consistent with the hypothesis that reduced exposure to ovulatory menstrual cycles provides a protective effect against breast cancer. Am J Epidemiol 1998; 147: 636–43. [ABSTRACT FROM AUTHOR]

The return of fertility for women who discontinue oral contraceptives takes longer as compared with women who discontinue other methods of contraception. It remains unclear, however, whether subsequent fertility differs according to duration or age at first use. The authors performed a nested case-control study within a cohort of 116,686 female registered nurses residing in 14 US states. Baseline information was reported on mailed questionnaires in 1989. Cases comprised 1,917 married nurses without previous pregnancy who were unable to become pregnant for at least 1 year and were subsequently diagnosed with primary ovulatory infertility. Controls comprised 44,521 married parous nurses with no history of infertility and no pregnancies lasting less than 6 months. After allowing for 2 years of suppressed fertility following discontinuation of oral contraceptive use and excluding women with signs of menstrual or hormonal disorder, the authors found that the multivariate relative risk for ovulatory causes of delayed fertility was 1.2 (95% confidence interval 0.7–1.9) for ever users. There was no statistically significant trend of increasing risk with increasing duration of use and younger age at first use. The fact that 88 percent of cases reported an eventual pregnancy by 1993 suggests that absolute fertility was not impaired. Am J Epidemiol 1997;146:258–65. [ABSTRACT FROM AUTHOR]

The article comments on a study by J. Ahn and colleagues on serum vitamin D concentrations and prostrate cancer risk. The research findings of Ahn's team do not support the hypothesis that higher vitamin D status is associated with lower risk of total or aggressive prostate cancer. However, the evidence suggests that increased vitamin D levels, through diet, supplementation and sun exposure, are likely to have a modest beneficial effect on the overall problem of chronic disease in the U.S.

Background: Plant-based diets are recommended for coronary heart disease (CHD) prevention. However, not all plant foods are necessarily beneficial for health.Objectives: This study sought to examine associations between plant-based diet indices and CHD incidence.Methods: We included 73,710 women in NHS (Nurses' Health Study) (1984 to 2012), 92,329 women in NHS2 (1991 to 2013), and 43,259 men in Health Professionals Follow-up Study (1986 to 2012), free of chronic diseases at baseline. We created an overall plant-based diet index (PDI) from repeated semiquantitative food-frequency questionnaire data, by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful plant-based diet index (hPDI) where healthy plant foods (whole grains, fruits/vegetables, nuts/legumes, oils, tea/coffee) received positive scores, whereas less-healthy plant foods (juices/sweetened beverages, refined grains, potatoes/fries, sweets) and animal foods received reverse scores. To create an unhealthful PDI (uPDI), we gave positive scores to less-healthy plant foods and reverse scores to animal and healthy plant foods.Results: Over 4,833,042 person-years of follow-up, we documented 8,631 incident CHD cases. In pooled multivariable analysis, higher adherence to PDI was independently inversely associated with CHD (hazard ratio [HR] comparing extreme deciles: 0.92; 95% confidence interval [CI]: 0.83 to 1.01; p trend = 0.003). This inverse association was stronger for hDPI (HR: 0.75; 95% CI: 0.68 to 0.83; p trend <0.001). Conversely, uPDI was positively associated with CHD (HR: 1.32; 95% CI: 1.20 to 1.46; p trend <0.001).Conclusions: Higher intake of a plant-based diet index rich in healthier plant foods is associated with substantially lower CHD risk, whereas a plant-based diet index that emphasizes less-healthy plant foods is associated with higher CHD risk. [ABSTRACT FROM AUTHOR]

Presents a study on the decline in the incidence of HIV-related wasting syndrome since the introduction of highly active antiretroviral therapy (HAART) in the U.S. Characteristics of weight loss in the later HAART use; Details on the clinical diagnosis of HIV wasting syndrome; Risk of weight loss.

Pre-exposure prophylaxis (PrEP) is underused in the southern United States (US), a region with high HIV incidence. Clinical decision support (CDS) tools could increase PrEP prescriptions. We explored barriers to PrEP delivery and views of CDS tools to identify refinements for implementation strategies for PrEP prescribing and PrEP CDS tools. We conducted focus groups with health care providers from two federally qualified health centers in Alabama and analyzed the results using rapid qualitative methods. Barriers to PrEP included providers' lack of training in PrEP, competing priorities and time constraints during clinical visits, concerns about side effects, and intensive workload. We identified refinements to the planned implementation strategies to address the barriers, including training all clinic staff in PrEP and having CDS PrEP alerts in electronic health records sent to all staff. Development and deployment of CDS tools in collaboration with providers has potential to increase PrEP prescribing in high-priority jurisdictions.

Importance: While increased adherence to colorectal cancer (CRC) screening guidelines in the US has been associated with significant reductions in cancer incidence in US individuals aged 50 years and older, the incidence of CRC among those aged younger than 50 years has been steadily increasing. Understanding the survival among individuals with early-onset CRC compared with those aged 50 years and older is fundamental to informing treatment approaches and understanding the unique biological distinctiveness within early-onset CRC., Objective: To characterize the overall survival for individuals with early-onset CRC., Design, Setting, and Participants: This cohort study used data from the National Cancer Database. Included individuals were ages 0 to 90 years and diagnosed with primary CRC from January 1, 2004, through December 31, 2015. Individuals diagnosed at ages 51 through 55 years were selected as the reference group and defined as later-onset CRC for this study. Individuals diagnosed at age 50 years were excluded to minimize an apparent screening detection bias at that age in our population, given that these individuals disproportionately presented with earlier stage. All statistical analyses were conducted from January 4, 2020, through December 26, 2020., Exposures: Early-onset CRC was defined as age younger than 50 years at diagnosis., Main Outcomes and Measures: Overall survival was assessed by Kaplan-Meier analysis and Cox proportional hazards regression., Results: Among 769 871 individuals with CRC (377 890 [49.1%] women; 636 791 White individuals [82.7%]), 353 989 individuals (46.0%) died (median [range] follow-up: 2.9 [0-14.0] years), 102 168 individuals (13.3%) had early-onset CRC, and 78 812 individuals (10.2%) had later-onset CRC. Individuals with early-onset CRC, compared with those diagnosed with CRC at ages 51 through 55 years, had a lower 10-year survival rate (53.6% [95% CI, 53.2%-54.0%] vs 54.3% [95% CI, 53.8%-54.8%]; P < .001) in unadjusted analysis. However, after adjustment for other factors associated with mortality, most notably stage, individuals with early-onset CRC had a lower risk of death compared with individuals diagnosed from ages 51 through 55 years (adjusted hazard ratio [HR], 0.95 [95% CI, 0.93-0.96]; P < .001). In the model adjusted for stage, the HR for individuals with early-onset CRC was 0.89 (95% CI, 0.88-0.90; P < .001). The survival advantage was greatest for individuals diagnosed at ages 35 through 39 years (adjusted HR, 0.88 [95% CI, 0.84-0.92]; P < .001) and stages I (adjusted HR, 0.87 [95% CI, 0.81-0.93]; P < .001) and II (adjusted HR, 0.86 [95% CI, 0.82-0.90]; P < .001) and was absent among those diagnosed at ages 25 years or younger and stages III through IV., Conclusions and Relevance: These findings suggest that there is a survival benefit for individuals with early-onset CRC compared with those diagnosed with CRC at later ages. Further study is needed to understand the underlying heterogeneity of survival among individuals with early-onset CRC by age and stage.

Importance: From 2004 to 2014, the US President's Emergency Plan for AIDS Relief (PEPFAR) invested more than $248 000 000 in the prevention of mother-to-child transmission (PMTCT) of HIV in Kenya. Concurrently, child mortality in Kenya decreased by half., Objective: To identify the extent to which the decrease in child mortality in Kenya is associated with PEPFAR funding for PMTCT of HIV., Design, Setting, and Participants: This population-based survey study conducted in Kenya estimated the association between annual per capita PEPFAR funding for PMTCT (annual PCF) and cumulative per capita PEPFAR funding for PMTCT (cumulative PCF), extracted using 2004-2014 country operational reports as well as individual-level health outcomes, extracted from the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys and the 2007 and 2012 Kenya AIDS Indicator Surveys. The study included children of female respondents to the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys who were born 1 to 60 months (for neonatal mortality) or 12 to 60 months (for infant mortality) before the survey, as well as female respondents who had recently given birth and reported on HIV testing during antenatal care (ANC) during the 2007-2014 surveys. Results were adjusted for year, province, and survey respondent characteristics. Statistical analysis was performed from July 8, 2016, to December 10, 2018., Main Outcomes and Measures: Neonatal mortality was defined as death within the first month of life and infant mortality was defined as death within the first year of life. HIV testing during ANC was defined as receiving counseling on PMTCT, undergoing an HIV test, and receiving test results during ANC., Results: The analysis included 33 181 neonates (16 870 boys), 26 876 infants (13 679 boys), and 20 775 mothers (mean [SD] age, 28.0 [6.7] years). PEPFAR funding was not associated with neonatal mortality. A $0.33 increase in annual PCF, corresponding to the difference between the 75th and 25th (interquartile range) percentiles of funding, was significantly associated with a 16% (95% CI, 4%-27%) reduction in infant mortality after a 1-year lag. A 14% to 16% reduction persisted after 2- and 3-year lags, and comparable reductions were observed for unlagged and 1-year lagged cumulative PCF. An increase of 1 interquartile range in cumulative PCF was associated with a 7% (95% CI, 3%-11%) increase in HIV testing during ANC, which intensified with subsequent lags. Between 2004 and 2014, sustained funding levels of $0.33 annual PCF could have averted 118 039 to 273 924 infant deaths., Conclusions and Relevance: Evidence from publicly available data suggests that PEPFAR's PMTCT funding was associated with a reduction in infant mortality and an increase in HIV testing during ANC in Kenya. The full outcome of funding may not be realized until several years after allocation.

Background: Hypertensive disorders of pregnancy (HDP) affect 10% to 15% of women and are associated with a 2-fold increased risk of cardiovascular disease (CVD)., Objectives: This study sought to determine whether inclusion of HDP in an established CVD risk score improves prediction of CVD events in women., Methods: The analysis comprised 106,230 ≤10-year observations contributed by 67,406 women, age ≥40 years, free of prior CVD, with data available on model covariates in the Nurses' Health Study II. Participants were followed up for confirmed myocardial infarction, fatal coronary heart disease, or stroke from 1989 to 2013. We fit an established CVD risk prediction model (Model A: age, total cholesterol and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, diabetes mellitus) and compared it to the same model plus HDP and parity (Model B); Cox proportional hazards models were used to obtain predicted probabilities for 10-year CVD risk., Results: HDP and parity were associated with 10-year CVD risk independent of established CVD risk factors, overall and at ages 40 to 49 years. However, inclusion of HDP and parity in the risk prediction model did not improve discrimination (Model A: C-index = 0.691; Model B: C-index = 0.693; p value for difference = 0.31) or risk reclassification (net reclassification improvement = 0.4%; 95% confidence interval: -0.2 to 1.0%; p = 0.26)., Conclusions: In this first test of the clinical utility of HDP and parity in CVD risk prediction, additional inclusion of HDP and parity in an established risk score did not improve discrimination or reclassification in this low-risk population; this might be because of the known associations between HDP and established CVD risk factors in the reference model., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Long-term exposure to particulate matter less than 2.5 μm in diameter (PM2.5) has been consistently associated with risk of all-cause mortality. The methods used to assess exposure, such as area averages, nearest monitor values, land use regressions, and spatio-temporal models in these studies are subject to measurement error. However, to date, no study has attempted to incorporate adjustment for measurement error into a long-term study of the effects of air pollution on mortality., Methods: We followed 108,767 members of the Nurses' Health Study (NHS) 2000-2006 and identified all deaths. Biennial mailed questionnaires provided a detailed residential address history and updated information on potential confounders. Time-varying average PM2.5 in the previous 12-months was assigned based on residential address and was predicted from either spatio-temporal prediction models or as concentrations measured at the nearest USEPA monitor. Information on the relationships of personal exposure to PM2.5 of ambient origin with spatio-temporal predicted and nearest monitor PM2.5 was available from five previous validation studies. Time-varying Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 percent confidence intervals (95%CI) for each 10 μg/m(3) increase in PM2.5. Risk-set regression calibration was used to adjust estimates for measurement error., Results: Increasing exposure to PM2.5 was associated with an increased risk of mortality, and results were similar regardless of the method chosen for exposure assessment. Specifically, the multivariable adjusted HRs for each 10 μg/m(3) increase in 12-month average PM2.5 from spatio-temporal prediction models were 1.13 (95%CI:1.05, 1.22) and 1.12 (95%CI:1.05, 1.21) for concentrations at the nearest EPA monitoring location. Adjustment for measurement error increased the magnitude of the HRs 4-10% and led to wider CIs (HR = 1.18; 95%CI: 1.02, 1.36 for each 10 μg/m(3) increase in PM2.5 from the spatio-temporal models and HR = 1.22; 95%CI: 1.02, 1.45 from the nearest monitor estimates)., Conclusions: These findings support the large body of literature on the adverse effects of PM2.5, and suggest that adjustment for measurement error be considered in future studies where possible.

Previous studies have suggested that long-chain n-3 fatty acids derived from seafood are associated with a lower risk of mortality, CHD and stroke. Whether α-linolenic acid (ALA, 18 : 3n-3), a plant-derived long-chain essential n-3 fatty acid, is associated with a lower risk of these outcomes is unclear. The aim of the present study was to examine the associations of plasma phospholipid and dietary ALA with the risk of mortality, CHD and stroke among older adults who participated in the Cardiovascular Health Study, a cohort study of adults aged ≥ 65 years. A total of 2709 participants were included in the plasma phospholipid ALA analysis and 2583 participants were included in the dietary ALA analysis. Cox regression was used to assess the associations of plasma phospholipid and dietary ALA with the risk of mortality, incident CHD and stroke. In minimally and multivariable-adjusted models, plasma phospholipid ALA was found to be not associated with the risk of mortality, incident CHD or stroke. After adjustment for age, sex, race, enrolment site, education, smoking status, diabetes, BMI, alcohol consumption, treated hypertension and total energy intake, higher dietary ALA intake was found to be associated with a lower risk of total and non-cardiovascular mortality; on comparing the highest quintiles of dietary ALA with the lowest quintiles, the HR for total mortality and non-cardiovascular mortality were found to be 0·73 (95 % CI 0·61, 0·88) and 0·64 (95 % CI 0·52, 0·80), respectively. Dietary ALA was found to be not associated with the risk of cardiovascular mortality, incident CHD or stroke. In conclusion, the results of the present suggest study that dietary ALA, but not plasma phospholipid ALA, is associated with a lower risk of total and non-cardiovascular mortality in older adults.

Background: Prior studies suggest that circulating fatty acids may influence the risk of atrial fibrillation (AF), but little is known about the associations of circulating saturated fatty acids with risk of AF., Methods and Results: The study population included 2899 participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 years or older in the United States who were free of prevalent coronary heart disease and AF in 1992. Cox regression was used to assess the association of all the long-chain saturated fatty acids-palmitic acid (16:0), stearic acid (18:0), arachidic acid (20:0), behenic acid (22:0), and lignoceric acid (24:0)-with incident AF. During a median of 11.2 years of follow-up, 707 cases of incident AF occurred. After adjustment for other AF risk factors, higher levels of circulating 16:0 were associated with a higher risk of AF (hazard ratio comparing highest and lowest quartiles: 1.48; 95% CI: 1.18, 1.86). In contrast, higher levels of circulating 18:0, 20:0, 22:0, and 24:0 were each associated with a lower risk of AF. The hazard ratios (95% CI) for AF in the top and bottom quartiles were 0.76 (95% CI: 0.61, 0.95) for 18:0; 0.78 (95% CI: 0.63, 0.97) for 20:0; 0.62 (95% CI: 0.50, 0.78) for 22:0; and 0.68 (95% CI: 0.55, 0.85) for 24:0., Conclusions: Results from this prospective cohort study of older adults demonstrate divergent associations of circulating 16:0 versus longer-chain saturated fatty acids with incident AF, highlighting the need to investigate both determinants of these levels and potential pathways of the observed differential risk., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Exposure measurement error is a concern in long-term PM2.5 health studies using ambient concentrations as exposures. We assessed error magnitude by estimating calibration coefficients as the association between personal PM2.5 exposures from validation studies and typically available surrogate exposures., Methods: Daily personal and ambient PM2.5, and when available sulfate, measurements were compiled from nine cities, over 2 to 12 days. True exposure was defined as personal exposure to PM2.5 of ambient origin. Since PM2.5 of ambient origin could only be determined for five cities, personal exposure to total PM2.5 was also considered. Surrogate exposures were estimated as ambient PM2.5 at the nearest monitor or predicted outside subjects' homes. We estimated calibration coefficients by regressing true on surrogate exposures in random effects models., Results: When monthly-averaged personal PM2.5 of ambient origin was used as the true exposure, calibration coefficients equaled 0.31 (95% CI:0.14, 0.47) for nearest monitor and 0.54 (95% CI:0.42, 0.65) for outdoor home predictions. Between-city heterogeneity was not found for outdoor home PM2.5 for either true exposure. Heterogeneity was significant for nearest monitor PM2.5, for both true exposures, but not after adjusting for city-average motor vehicle number for total personal PM2.5., Conclusions: Calibration coefficients were <1, consistent with previously reported chronic health risks using nearest monitor exposures being under-estimated when ambient concentrations are the exposure of interest. Calibration coefficients were closer to 1 for outdoor home predictions, likely reflecting less spatial error. Further research is needed to determine how our findings can be incorporated in future health studies.

Objective: To examine the association between physical activity and risk of ulcerative colitis and Crohn's disease., Design: Prospective cohort study., Setting: Nurses' Health Study and Nurses' Health Study II., Participants: 194,711 women enrolled in the Nurses' Health Study and Nurses' Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses' Health Study and 1989 in the Nurses' Health Study II and followed up through 2010., Main Outcome Measure: Incident ulcerative colitis and Crohn's disease., Results: During 3,421,972 person years of follow-up, we documented 284 cases of Crohn's disease and 363 cases of ulcerative colitis. The risk of Crohn's disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn's disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn's disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn's disease among women in the highest fifth of physical activity was 8 and 6 events per 100,000 person years compared with 11 and 16 events per 100,000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn's disease (all P for interaction >0.35)., Conclusion: In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn's disease but not of ulcerative colitis.

Background: Few studies have examined the relationship of α-linolenic acid (ALA 18:3n-3), an intermediate-chain essential n-3 polyunsaturated fatty acid derived from plants and vegetable oils, with incident atrial fibrillation (AF)., Methods and Results: The study population included participants from the Cardiovascular Health Study, a community-based longitudinal cohort of adults aged 65 or older, free of prevalent coronary heart disease and atrial fibrillation. We assessed the associations of plasma phospholipid and dietary ALA with incident AF using Cox regression. The biomarker analysis comprised a total of 2899 participants, and the dietary analysis comprised 4337 participants. We found no association of plasma phospholipid ALA and incident AF. Comparing each of the second, third, and fourth quartiles to the lowest quartile, the hazard ratios for AF were 1.11 (95% CI, 0.90 to 1.37), 1.09 (95% CI, 0.88 to 1.35), and 0.92 (95% CI, 0.74 to 1.15), after adjustment for age, sex, race, clinic, education, smoking, alcohol, body mass index, waist circumference, diabetes, heart failure, stroke, treated hypertension, and physical activity (P trend=0.48). When dietary ALA was considered the exposure of interest, results were similar., Conclusions: Results from this prospective cohort study of older adults indicate no association of plasma phospholipid or dietary ALA and incident AF.

Background: Lesbian and bisexual women may be at greater risk of breast cancer than heterosexual women during the premenopausal period due to disparities in risk factors., Methods: With 16 years of prospective data from a large cohort of U.S. women ages 25-58 years, we conducted a breast cancer risk assessment for 87,392 premenopausal women by applying the Rosner-Colditz biomathematical risk prediction model to estimate breast cancer risk based on known risk factors. On the basis of each woman's comprehensive risk factor profile, we calculated the predicted 1-year incidence rate (IR) per 100,000 person-years and estimated incidence rate ratios (IRR) and 95% confidence intervals (CI) for lesbian and bisexual women compared with heterosexual women., Results: A total of 87,392 premenopausal women provided 1,091,871 person-years of data included in analyses. Mean predicted 1-year breast cancer IRs per 100,000 person-years for each sexual orientation group were heterosexual, 122.55; lesbian, 131.61; and bisexual, 131.72. IRs were significantly elevated in both lesbian (IRR, 1.06; 95% CI, 1.06-1.06) and bisexual (IRR, 1.10; 95% CI, 1.10-1.10) women compared with heterosexual women., Conclusions: Our findings suggest that both lesbian and bisexual women have slightly elevated predicted breast cancer incidence compared with heterosexual women throughout the premenopausal period., Impact: Health professionals must ensure that breast cancer prevention efforts are reaching these women. As more health systems around the country collect data on patient sexual orientation, the National Cancer Institute's SEER cancer registry should add this information to its data system to monitor progress in reducing sexual orientation-related disparities in cancer incidence and mortality.

Cross-sectional studies and animal experiments suggest that methylmercury exposure could increase the risk of hypertension. This relationship has not been evaluated in large prospective studies. Using data from previous nested case-control studies in 2 separate prospective cohorts, we measured toenail mercury, a valid biomarker of long-term methylmercury exposure, among 6045 US men and women free of hypertension at baseline. Geometric mean toenail mercury concentrations were 0.08 μg/g in the lowest quintile and 0.74 μg/g in the highest quintile, the latter corresponding with exposures ≈2.0-fold higher than the US Environmental Protection Agency reference dose. Participants were followed prospectively (mean±SD follow-up, 14.9±7.9 years) for a new self-report of physician-diagnosed hypertension (3540 cases), shown to be >95% sensitive and specific for diagnosing hypertension in these cohorts as compared with review of medical charts and direct blood pressure measurement, respectively. After adjustment for demographic, clinical, and lifestyle risk factors, the hazard ratio (95% CI) for incident hypertension in the highest versus lowest quintile of mercury exposure was 0.96 (0.84-1.09) in women, 0.82 (0.62-1.08) in men, and 0.94 (0.84-1.06) in both cohorts combined. Findings were similar when more extreme categories of mercury were compared (across deciles, with geometric mean levels in highest decile ≈2.9-fold higher than the reference dose) and in analyses stratified by fish or omega-3 consumption, selenium levels, body mass index, and age. These findings from 2 separate large prospective cohort studies do not support any clinically apparent adverse effects of methylmercury exposure on the risk of hypertension in men or women, including at levels ≤2.5-fold higher than the reference dose.

Background: Few studies have evaluated the association between the n-3 fatty acid α-linolenic acid (ALA) and the incidence of congestive heart failure (CHF)., Objective: We investigated whether plasma phospholipid concentrations and estimated dietary consumption of ALA are associated with incident CHF., Design: We used data from the Cardiovascular Health Study, a prospective cohort study of cardiovascular diseases among adults aged ≥65 y, from 4 US communities. A total of 2957 participants free of prevalent heart disease and with available fatty acid measurements were included in biomarker analyses (30,722 person-years and 686 incident CHF events). A total of 4432 participants free of prevalent heart disease were included in dietary analyses (52,609 person-years and 1072 events). We investigated the association of ALA with incident CHF by using Cox regression., Results: After adjustment for age, sex, race, education, smoking status, BMI, waist circumference, and alcohol consumption, plasma phospholipid ALA was not associated with incident CHF (HR for the highest compared with the lowest quartile: 0.97; 95% CI: 0.79, 1.21; P-trend = 0.85). Likewise, dietary ALA was not associated with incident CHF (adjusted HR for the highest compared with the lowest quartile: 0.96; 95% CI: 0.82, 1.20; P-trend = 0.97). We observed no association of biomarker or dietary ALA with nonvalvular CHF subtype. We also found little evidence of an association between ALA and CHF in subgroups based on age, sex, diabetes, fish consumption, BMI, or FADS2 genotype (rs1535)., Conclusion: ALA intake is not associated with incident CHF in older adults. This trial was registered at clinicaltrials.gov as NCT00005133.

Background: This study investigated the relationship between growing up in a violent home and developmental trajectories of body mass index (BMI) in a cohort of adolescents followed longitudinally from 1996 to 2003-4., Methods: 6043 girls and 4934 boys aged 9-14 years in 1996 who reported height and weight at least two times and whose mothers completed intimate partner violence (IPV) questions at the 2001 Nurses' Health Study. Main exposure was experiencing the first family violence during early (0-5 years) or later (6-11 years) childhood, based on mother's year-specific exposure of IPV and the birth year of each participant. Mother's report of IPV was ascertained by the abuse assessment screen. Four distinct BMI trajectory groups were estimated from age-specific BMI (age 12-20 years), using general growth mixture modelling., Results: Four distinct BMI trajectories were identified separately for girls and boys: healthy growth; healthy to obese; steady overweight and consistently obese. Compared with boys not exposed to violence at home, boys raised in violent homes before 5 years were at increased risk of being in the consistently obese (OR =2.0; 95% CI 1.2 to 3.5) and steady overweight (OR 1.4; 95% CI 1.1 to 1.9) groups after adjusting for confounders. Girls raised in violent homes were more likely to be in the steady overweight group, but associations did not maintain statistical significance after adjusting for confounding., Conclusion: These data link children's exposure to domestic violence to a risk of unhealthy weight trajectories during adolescence in boys. Detrimental effects of exposure to a domestic violence environment may take root in the first few years of development for boys.

Two alkylresorcinol (AR) metabolites, 3, 5-dihydroxybenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), in urine have been suggested as biomarkers of whole grain (WG) and cereal fiber intake but the long-term reproducibility and correlation with habitual intake has not been determined. Therefore, we evaluated the long-term reproducibility of AR metabolites in spot urine samples and investigated their correlation with habitual WG and cereal fiber intake in U.S. women. AR metabolites were analyzed in 104 women participating in the Nurses' Health Study II and WG and fiber intakes were assessed using a FFQ. Long-term reproducibility was assessed by calculating the intra-class correlation coefficients (ICC) using samples taken 1-3 y (mean 1.8 y) apart. The observed Spearman correlation coefficients (r(s)) and r(s) adjusted for within-participant variation in the biomarker were calculated between WG and fiber intake and biomarkers. The long-term reproducibility was poor for DHBA [ICC = 0.17 (95% CI: 0.05, 0.43)] and modest for DHPPA [ICC = 0.31 (95% CI: 0.17, 0.51)]. The correlation between WG intake in 1995 and DHPPA measured 2 y later was 0.37 (P < 0.0001); the adjusted correlation was 0.60 (95% CI: 0.37, 0.76). Cereal fiber and WG intake were similarly correlated to the biomarkers. DHPPA in spot urine samples reflected WG intake despite relatively low intake of food sources of AR. The poor to modest reproducibility may limit the use of single measurements of these biomarkers in cohort studies in the US, where WG intake is relatively low and has changed over time. But DHPPA in repeated samples may be useful for validating WG intake and assessing compliance in WG intervention studies.

Background: Few studies have directly assessed the association of secondhand smoke (SHS) with cardiovascular disease-related inflammatory markers, and the findings are inconsistent., Objectives: We assessed the association between SHS exposure and the inflammatory markers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) in 199 nonsmoking U.S. trucking industry workers., Methods: Participants provided blood samples either by mail (blood drawn at local health care provider near home) or at the work site (blood drawn by research staff on-site) and completed a health and work history questionnaire at the time of blood draw. Exposure to SHS was measured by plasma cotinine concentrations. We used multivariate regression analyses to assess the associations between levels of cotinine and inflammatory markers., Results: The median cotinine level was 0.10 ng/mL (interquartile range, 0.04-0.23 ng/mL). The odds ratios of elevated hs-CRP (above highest CRP tertile, 1.5 mg/L) were 2.85 [95% confidence interval (CI), 1.03-7.89] for the high-cotinine group (> 0.215 ng/mL) and 2.80 (95% CI, 1.11-7.10) for the moderate-cotinine group (0.05-0.215 ng/mL), compared with the low-cotinine group (< 0.05 ng/mL), adjusting for age, sex, race, educational level, obesity, previous smoking history, job title, and medical history. Plasma cotinine levels were not associated with IL-6 or sICAM-1., Conclusions: SHS exposure, as assessed by plasma cotinine, was positively associated with hs-CRP in this group of blue-collar workers. The strength of the association with hs-CRP depended on the cut points selected for analysis.

The authors prospectively examined the relation of fruit and vegetable intake to breast cancer risk among 51,928 women aged 21-69 years at enrollment in 1995 in the Black Women's Health Study. Dietary intake was assessed by using a validated food frequency questionnaire. Cox proportional hazards models were used to estimate incidence rate ratios and 95% confidence intervals, adjusted for breast cancer risk factors. During 12 years of follow-up, there were 1,268 incident cases of breast cancer. Total fruit, total vegetable, and total fruit and vegetable intakes were not significantly associated with overall risk of breast cancer. However, total vegetable consumption was associated with a decreased risk of estrogen receptor-negative/progesterone receptor-negative breast cancer (incidence rate ratio = 0.57, 95% confidence interval: 0.38, 0.85, for ≥2 servings/day relative to <4/week; P(trend) = 0.02). In addition, there was some evidence of inverse associations with breast cancer risk overall for cruciferous vegetable intake (P(trend) = 0.06) and for carrot intake (P(trend) = 0.02). Study findings suggest that frequent consumption of vegetables is inversely associated with risk of estrogen receptor-negative/progesterone receptor-negative breast cancer, and that specific vegetables may be associated with a decreased risk of breast cancer overall.

Background: Prospective studies in US women have suggested an inverse relation between dietary protein and risk of ischemic heart disease (IHD). However, no large-scale prospective studies have been conducted in US men., Objective: The objective was to examine the association between dietary protein and risk of IHD in a prospective study of US men., Design: Intakes of protein and other nutrients were assessed by using a validated food-frequency questionnaire at 4 time points during follow-up of 43,960 men participating in the Health Professionals Follow-Up Study. Cox proportional hazards models were used to calculate multivariable-adjusted relative risks (RRs) and 95% CIs., Results: During 18 y of follow-up, we documented 2959 incident cases of IHD. The RR of IHD was 1.08 (95% CI: 0.95, 1.23; P for trend = 0.30) comparing the top with the bottom quintile of percentage of energy from total protein. RRs for animal and vegetable protein were 1.11 (95% CI: 0.97, 1.28; P for trend = 0.18) and 0.93 (95% CI: 0.78, 1.12; P for trend = 0.49), respectively. When the population was restricted to "healthy" men (those free of hypertension, hypercholesterolemia, and diabetes at baseline), the RR of IHD was 1.21 (95% CI: 1.01, 1.44; P for trend = 0.02) for total protein, 1.25 (95% CI: 1.04, 1.51; P for trend = 0.02) for animal protein, and 0.93 (95% CI: 0.72, 1.19; P for trend = 0.65) for vegetable protein., Conclusions: We observed no association between dietary protein and risk of total IHD in this group of men aged 40-75 y. However, higher intake of animal protein may be associated with an increased risk of IHD in "healthy" men.

Background: Previous studies convincingly showed an increase in risk of breast cancer associated with current or recent use of oral contraceptives from the 1960s to 1980s. The relation of contemporary oral contraceptive formulations to breast cancer risk is less clear., Methods: We assessed lifetime oral contraceptive use and the specific formulations used among 116,608 female nurses ages 25 to 42 years at enrollment in 1989, and subsequently updated this information every 2 years. We related this information to risk of breast cancer up to June 1, 2001., Results: During 1,246,967 person-years of follow-up, 1,344 cases of invasive breast cancer were diagnosed. Past use of any oral contraceptive was not related to breast cancer risk [multivariate relative risk (RR), 1.12; 95% confidence interval 0.95-1.33]. Current use of any oral contraceptive was related to a marginally significant higher risk (multivariate RR, 1.33; 95% CI, 1.03-1.73). One specific formulation substantially accounted for the excess risk: the RR for current use of triphasic preparations with levonorgestrel as the progestin was 3.05 (95% CI, 2.00-4.66; P < 0.0001)., Conclusions: Current use of oral contraceptives carries an excess risk of breast cancer. Levonorgestrel used in triphasic preparations may account for much of this elevation in risk., Impact: Different oral contraceptive formulations might convey different risks of breast cancer; ongoing monitoring of these associations is necessary as oral contraceptive formulations change., (©2010 AACR.)

Background & Aims: Peptic ulcer disease has been associated with an increased risk of pancreatic cancer, but findings on this topic are inconsistent. We investigated the association between pancreatic cancer and the occurrence of gastric or duodenal ulcer in a large US cohort., Methods: We analyzed data collected from 51,529 male health professionals in a prospective cohort study. History of peptic ulcer disease was assessed at baseline in 1986 and updated biennially thereafter. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models adjusting for smoking, body mass index, diabetes, and physical activity., Results: During 18 years of follow-up evaluation, we observed 274 incident pancreatic cancer cases. Compared with those with report of no peptic ulcer disease, men with gastric ulcer had an increased risk of pancreatic cancer (RR, 1.83; 95% CI, 1.13-2.97). Although the risk was highest for those with a diagnosis of gastric ulcer that was close in time to the cancer diagnosis (RR, 3.66; 95% CI, 1.45-9.24), the risk remained significantly increased 10-19 years after the gastric ulcer diagnosis (RR, 2.89; 95% CI, 1.26-6.64). In contrast, duodenal ulcer was not associated with pancreatic cancer risk (RR, 1.15; 95% CI, 0.78-1.71)., Conclusions: Gastric ulcer increases the risk of pancreatic cancer, whereas there does not appear to be an association between duodenal ulcers and pancreatic cancer.

Background: Although the smoking rate in the United States is declining because of an increase of smoke-free laws, among blue-collar workers it remains higher than that among many other occupational groups., Objectives: We evaluated the factors influencing workplace secondhand smoke (SHS) exposures in the U.S. unionized trucking industry., Methods: From 2003 through 2005, we measured workplace SHS exposure among 203 nonsmoking and 61 smoking workers in 25 trucking terminals. Workers in several job groups wore personal vapor-phase nicotine samplers on their lapels for two consecutive work shifts and completed a workplace SHS exposure questionnaire at the end of the personal sampling., Results: Median nicotine level was 0.87 microg/m3 for nonsmokers and 5.96 microg/m3 for smokers. As expected, smokers experienced higher SHS exposure duration and intensity than did nonsmokers. For nonsmokers, multiple regression analyses indicated that self-reported exposure duration combined with intensity, lack of a smoking policy as reported by workers, having a nondriver job, and lower educational level were independently associated with elevated personal nicotine levels (model R2 = 0.52). Nondriver job and amount of active smoking were associated with elevated personal nicotine level in smokers, but self-reported exposure, lack of a smoking policy, and lower educational level were not., Conclusions: Despite movements toward smoke-free laws, this population of blue-collar workers was still exposed to workplace SHS as recently as 2005. The perceived (reported by the workers), rather than the official (reported by the terminal managers), smoking policy was associated with measured SHS exposure levels among the nonsmokers. Job duties and educational level might also be important predictors of workplace SHS exposure.

Background: Diet is a key component of a healthy lifestyle in the prevention of type 2 diabetes mellitus (T2DM). The role of long-chain omega-3 (n-3) fatty acids (LCFAs) in the development of T2DM remains unresolved., Objective: We examined the association between dietary LCFAs and incidence of T2DM in 3 prospective cohorts of women and men., Design: We followed 195,204 US adults (152,700 women and 42,504 men) without preexisting chronic disease at baseline for 14 to 18 y. Fish and LCFA intakes were assessed at baseline and updated at 4-y intervals by using a validated food-frequency questionnaire., Results: During nearly 3 million person-years of follow-up, 9380 new cases of T2DM were documented. After adjustment for other dietary and lifestyle risk factors, LCFA intake was positively related to incidence of T2DM. The pooled multivariate relative risks in 3 cohorts across increasing quintiles of LCFAs were as follows: 1 (reference), 1.00 (95% CI: 0.91, 1.09), 1.05 (95% CI: 0.97, 1.13), 1.17 (95% CI: 1.07, 1.28), and 1.24 (95% CI: 1.09, 1.40) (P for trend < 0.001). Compared with those who consumed fish less than once per month, the relative risk of T2DM was 1.22 (95% CI: 1.08, 1.39) for women who consumed > or =5 servings fish/wk (P for trend <0.001)., Conclusions: We found no evidence that higher consumption of LCFAs and fish reduces the risk of T2DM. Instead, higher intakes may modestly increase the incidence of this disease. Given the beneficial effects of LCFA intake on many cardiovascular disease risk factors, the clinical relevance of this relation and its possible mechanisms require further investigation.

Background: Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance., Objective: We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD., Design: This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD., Results: During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found., Conclusion: The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.

Background: Results of several case-control studies suggest that high consumption of meat (all meat, red meat, or processed meat) is associated with an increased risk of renal cell cancer, but only a few prospective studies have examined the associations of intakes of meat, fat, and protein with renal cell cancer., Methods: We conducted a pooled analysis of 13 prospective studies that included 530,469 women and 244,483 men and had follow-up times of up to 7-20 years to examine associations between meat, fat, and protein intakes and the risk of renal cell cancer. All participants had completed a validated food frequency questionnaire at study entry. Using the primary data from each study, we calculated the study-specific relative risks (RRs) for renal cell cancer by using Cox proportional hazards models and then pooled these RRs by using a random-effects model. All statistical tests were two-sided., Results: A total of 1,478 incident cases of renal cell cancer were identified (709 in women and 769 in men). We observed statistically significant positive associations or trends in pooled age-adjusted models for intakes of total fat, saturated fat, monounsaturated fat, polyunsaturated fat, cholesterol, total protein, and animal protein. However, these associations were attenuated and no longer statistically significant after adjusting for body mass index, fruit and vegetable intake, and alcohol intake. For example, the pooled age-adjusted RR of renal cell cancer for the highest vs the lowest quintile of intake for total fat was 1.30 (95% confidence interval [CI] = 1.08 to 1.56; P(trend) = .001) and for total protein was 1.17 (95% CI = 0.99 to 1.38; P(trend) = .02). By comparison, the pooled multivariable RR for the highest vs the lowest quintile of total fat intake was 1.10 (95% CI = 0.92 to 1.32; P(trend) = .31) and of total protein intake was 1.06 (95% CI = 0.89 to 1.26; P(trend) = .37). Intakes of red meat, processed meat, poultry, or seafood were not associated with the risk of renal cell cancer., Conclusions: Intakes of fat and protein or their subtypes, red meat, processed meat, poultry, and seafood are not associated with risk of renal cell cancer.