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We aimed to examine the association between the use of metformin and other anti‐diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti‐diabetes medications, and other covariates was self‐reported at baseline and repeatedly assessed by follow‐up questionnaires every 2 years. Breast cancer cases were self‐reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person‐years of follow‐up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti‐diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2‐year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D. [ABSTRACT FROM AUTHOR]

Purpose: Metabolomic and preclinical studies suggest that branched‐chain amino acids (BCAA) may be inversely associated with neurodegenerative diseases including glaucoma. We therefore assessed the long‐term association between dietary intake of BCAA and incident primary open‐angle glaucoma (POAG) and POAG subtypes. Methods: We followed biennially participants of the Nurses' Health Study (NHS; 65 531 women: 1984–2016), Health Professionals Follow‐up Study (42 254 men: 1986–2016) and NHSII (66 904 women; 1991–2017). Eligible participants were 40+ years old and reported eye examinations. Repeated validated food frequency questionnaires were used to assess dietary intake of BCAA. Incident cases of POAG and POAG subtypes defined by visual field (VF) loss and untreated intraocular pressure (IOP) were confirmed by medical record review. Multivariable‐adjusted relative risks (MVRRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results: We identified 1946 incident POAG cases. The pooled MVRRs of POAG for the highest quintile (Q5 = 17.1 g/day) versus lowest quintile (Q1 = 11.2 g/day) of total BCAA intake was 0.93 (95% CI, 0.73–1.19; ptrend = 0.45; pheterogeneity by sex = 0.24). For subtypes of POAG defined by IOP level or POAG with only peripheral VF loss, no associations were observed for men or women (ptrend ≥ 0.20); however, for the POAG subtype with early paracentral VF loss, there was a suggestion of an inverse association in women (MVRRQ5versusQ1 = 0.80 [95% CI, 0.57–1.12; ptrend = 0.12]) but not in men (MVRRQ5versusQ1 = 1.38 [95% CI, 0.81–2.34; ptrend = 0.28; pheterogeneity by sex = 0.06]). Conclusion: Higher dietary intake of BCAA was not associated with POAG risk. [ABSTRACT FROM AUTHOR]

Introduction:: Few large, randomized trials have evaluated marine n-3 supplements and cognition in healthy older adults. Methods:: Healthy community-dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.8] years) in VITAL (randomized trial of n-3 fats [1 g/day, including 840 mg of eicosapentaenoic acid + docosahexaenoic acid] and vitamin D) were included: 3424 whose cognition was assessed by phone (VITAL-Cog; eight neuropsychological tests; 2.8 years) and 794 evaluated in person (CTSC-Cog; nine tests; 2.0 years). The primary outcome was a global score (average of test z-scores) of change over two assessments. We used multivariable-adjusted linearmixed models; substudyspecific results weremeta-analyzed. Results: :We observed no significant effect of n-3 supplementation: the mean difference in annual rate of cognitive change for the n-3 versus placebo group was -0.01 standard units (95% confidence interval [CI]: -0.02, 0.003) in VITAL-Cog and -0.002 (95% CI: -0.04, 0.03) in CTSC-Cog; the pooled difference was -0.01 (95% CI: -0.02, 0.003; P = .15). Discussion:: Marine n-3 supplementation (1 g/day) did not confer cognitive benefits over 2 to 3 years in community-dwelling older adults. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: Relatively little is known regarding predictors of advance care planning (ACP) in former nurses. We aimed to evaluate potential predictors of ACP documentation and discussion. DESIGN: Cross‐sectional study, 2012‐2014. SETTING: Nurses' Health Study. PARTICIPANTS: A total of 60,917 community‐dwelling female nurses aged 66 to 93 years living across the United States. MEASUREMENTS: Based on self‐reports, participants were categorized as having (1) only ACP documentation, (2) ACP documentation and a recent ACP discussion with a healthcare provider, or (3) neither. Multivariable log‐binomial models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) of the two separate ACP categories vs those with neither. We evaluated various demographic, health, and social factors. RESULTS: The large majority (84%) reported ACP documentation; 35% reported a recent ACP discussion. Demographic factors such as age and race were associated with both ACP categories. In multivariable analyses, race was most strongly associated: compared with whites, African Americans were 27% less likely (PR = 0.73; 95% CI = 0.69‐0.78) to report ACP documentation alone and 41% (PR = 0.59; 95% CI = 0.54‐0.66) less likely to report documentation with discussion. Additionally, health/healthcare‐related characteristics were more strongly associated with ACP documentation plus discussion. Women with functional limitations (PR = 1.15; 95% CI = 1.10‐1.20), women who were recently hospitalized (PR: 1.10; 95% CI = 1.08‐1.12) or women who had seen a physician for health symptoms (PR = 1.43; 95% CI = 1.35‐1.52) or screening (PR = 1.40; 95% CI = 1.32‐1.49) were more likely to report having both ACP documentation and discussion. Social factors showed limited relationships with ACP documentation only; for documentation plus discussion, being widowed and living alone was associated with higher prevalence (PR = 1.21; 95% CI = 1.19‐1.24) and having little emotional support was associated with lower prevalence (PR = 0.84; 95% CI = 0.81‐0.86). CONCLUSIONS: Among older nurses, most of whom reported having documented ACP, 35% reported recent patient‐clinician ACP discussions, indicating a major participatory gap in an element critical to ACP effectiveness. Even in nurses, African Americans reported less ACP documentation or discussion. J Am Geriatr Soc 67:292–301, 2019. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the association between flavonoid intake and incident primary open‐angle glaucoma (POAG). Methods: We followed 65 516 women from the Nurses' Health Study (from 1984) and 42 156 men from the Health Professionals Follow‐up Study (from 1986) biennially to 2012, who were 40+ years old, free of POAG, and reported eye examinations. Dietary flavonoid intake was assessed with validated repeated semi‐quantitative food frequency questionnaires. Incident POAG cases (n = 1575) were confirmed with medical record review. Cohort‐specific multivariable‐adjusted relative risks (RRs) and 95% confidence intervals (CIs) were calculated and meta‐analysed. Results: Total flavonoid intake was not associated with risk of POAG development [RR for highest (Q5: median ~645 mg/day) versus lowest quintile (Q1: ~130 mg/day) = 0.91 (95% CI = 0.77, 1.08); p for trend (p‐trend) = 0.19]; the flavonoid subclasses of flavones, flavanones, polymeric flavanols or anthocyanidins were also not associated (Q5 versus Q1 comparison p‐values ≥0.05 and p‐trend ≥0.09). Higher intakes of flavonols and monomeric flavanols were nominally associated with lower POAG risk, based on the Q5 versus Q1 comparisons or p‐trends. The Q5 versus Q1 comparison RRs were: for flavonols, 0.82 (95% CI = 0.69, 0.97; p‐trend = 0.05; ~28 versus ~8 mg/day), and for monomeric flavanols, 0.86 (95% CI = 0.72, 1.02; p‐trend=0.04; ~110 versus 10 mg/day). The food/beverage that contributed most to both the variation of flavonols and monomeric flavanols was tea; consuming ~2 cups/day was associated with 18% lower POAG risk (RR=0.82; 95% CI = 0.68, 0.99; p‐trend = 0.02). Conclusion: Total flavonoid intake was not associated with POAG risk. Greater intakes of flavonols and monomeric flavanols and of tea showed suggestive modest associations with lower risk; these results need confirmation. [ABSTRACT FROM AUTHOR]

Abstract: Advanced glycation end products (AGEs) are formed upon nonenzymatic reactions of sugars or their metabolites with proteins and other cellular constituents. Many AGEs are long lived. Recent findings suggest that AGEs may predict diabetes and its complications and thus may warrant further study. The objective of this study was to assess the validity of our experimental procedures for measuring AGEs in stored blood sample and to conduct a pilot study for developing AGE biomarkers for diabetes and/or age‐related changes of glucose metabolism. We conducted a reliability study of the samples and methods using liquid chromatography–tandem mass spectrometry (LC‐MS)/MS assays for 10 AGEs (including methylglyoxal‐derived hydroimidazolone (MG‐H1), glucosepane (GSP) and two oxidation measures, in stored repository blood samples from the Nurses' Health Study and the Health Professionals Follow‐up Study. We also analyzed data relating blood GSP levels to type 2 diabetes status in a case‐control study (25 cases and 15 controls). Among the AGEs, GSP, and MG‐H1 showed the highest reliability across the various measures: reliability in duplicate samples and stability with delayed processing and storage over 1–2 year period. Furthermore, plasma GSP was associated with older age (P = 0.04) and type 2 diabetes status (age‐adjusted P = 0.0475). Our findings suggest that analysis of these AGEs may be developed as biomarkers for diabetes and/or age‐related changes of glucose metabolism. © 2018 BioFactors, 44(3):281–288, 2018 [ABSTRACT FROM AUTHOR]

Objective: A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders. Methods: Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake. Results: Higher SFA intake was associated with worse global cognitive ( p for linear trend = 0.008) and verbal memory ( p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04-2.58) for global cognition and 1.65 (1.04-2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive ( p for linear trend < 0.001) and verbal memory ( p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31-0.88]) and verbal memory (0.56 [0.34-0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive trajectory. Interpretation: Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging. ANN NEUROL 2012; [ABSTRACT FROM AUTHOR]

Summary Reproductive factors are associated with seizures in women with epilepsy. We prospectively examined the association between reproductive factors and the risk of adult-onset isolated seizure, epilepsy, or any unprovoked seizure (defined as single unprovoked seizure or epilepsy) among 114,847 Nurses' Health Study II participants followed from 1989 to 2005. Validated seizure questionnaires and medical records were used to confirm incident cases of isolated seizure (n = 95) or epilepsy (n = 151). Overall, there were no significant associations between any reproductive factor and risk of any unprovoked seizure (n = 196). However, menstrual irregularity at ages 18-22 years was specifically associated with an increased risk of epilepsy [relative risk (RR) 1.67, 95% confidence interval (CI) 1.12-2.51]. Menstrual irregularity during follow-up (RR 2.21, 95% CI 1.16-4.20) and early age at menarche (<12 years vs. 12-13 years; RR 1.76, 95% CI 1.10-2.81) increased the risk of isolated seizure. Oral contraceptive use and parity were not associated with isolated seizure or epilepsy. Therefore, menstrual factors were associated with risk of seizure and epilepsy. [ABSTRACT FROM AUTHOR]

Visceral adipose tissue-derived serpin (vaspin) has been regarded as a novel adipokine with potential insulin sensitizing properties. We investigated the changes of serum vaspin concentration in response to weight reduction, and the associations between changes in serum vaspin concentrations and changes of anthropometric and metabolic variables in obese subjects after weight reduction. We performed a longitudinal clinical intervention study on 63 obese persons enrolled in a 12-week weight reduction program that included lifestyle modification and adjuvant treatment with the antiobesity agent orlistat. Anthropometric variables, lipid profiles, fasting glucose, fasting insulin, and serum vaspin concentrations were measured. Statistical analyses were performed according to the homeostasis model assessment of insulin resistance (HOMAIR). Serum vaspin concentrations decreased significantly in responders (≥2% reduction in baseline weight), but not in nonresponders (<2% reduction in baseline weight). Changes in serum vaspin concentrations were significantly correlated with body weight, BMI, waist circumference, and hip circumference in the higher, but not in the lower, HOMAIR group. In multivariate linear regression analysis, change in serum vaspin concentrations in the higher, but not in the lower, HOMAIR group was positively correlated with change in BMI and negatively correlated with initial HOMAIR level. The associations between changes in serum vaspin concentrations and changes in anthropometric and metabolic parameters differed according to insulin resistance status in obese subjects. These relationships were more prominent in the higher HOMAIR group. Insulin resistance may influence the correlations between changes in serum vaspin concentration and related metabolic variables. [ABSTRACT FROM AUTHOR]

Seizures and epilepsy are associated with significant disability and substantial treatment costs, yet little is known about primary prevention. We prospectively examined the association of cigarette smoking, caffeine use, and alcohol intake with risk of seizure or epilepsy among women, aged 25–42 years, in the Nurses’ Health Study II. Participants provided dietary and cigarette smoking information on multiple questionnaires beginning in 1989. Among 116,363 women at-risk for incident seizure or epilepsy, we confirmed 95 cases of seizure and 151 cases of epilepsy occurring from 1989–2005 using information from a detailed supplementary questionnaire and medical records. Multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Compared with never smoking, current cigarette smoking was associated with an increased risk of seizure (RR 2.60, 95% CI 1.53–4.42), after adjustment for stroke and other potential confounding factors. Past smoking was not associated with risk of seizure, but was associated with modestly increased risk of epilepsy (RR 1.46, 95% CI 1.01–2.12). Long-term caffeine and moderate alcohol intake were not associated with seizure or epilepsy. Cigarette smoking may be associated with increased risk of seizure. More prospective studies are needed to investigate potential factors to ultimately prevent the development of seizures or epilepsy. [ABSTRACT FROM AUTHOR]

To investigate the associations of uncoupling protein (UCP)2 and UCP3 gene variants with overweight and related traits, we genotyped UCP2−866G>A, UCP2Ala55Val, and UCP3−55C>T in 737 Korean children and 732 adults and collected data regarding anthropometric status and blood biochemistry. Information concerning the children's lifestyles and dietary habits was collected. The UCP2−866G>A and UCP3−55C>T gene variants showed significant associations with BMI level, waist circumference, and body weight in the children but not in the adults. Compared with −866GG carriers, the −866GA and AA carriers showed a strong decreasing trend in the risk for overweight (odds ratio (OR), 0.67; 95% confidence interval (CI), 0.45–1.01; P = 0.053). In comparison with UCP3−55CC carriers, children carrying −55CT and TT showed a significant reduction in the risk of overweight (OR, 0.67; 95% CI, 0.46–0.98; P = 0.039). There was also evidence of interactions between the effects of the combined UCP2−UCP3 genotype and obesity-related metabolic traits. The greatest protective effect against overweight was seen in those with the combined genotype non-UCP2−866GG and non-UCP3−55CC, as compared with those carrying both UCP2−866GG and UCP3−55CC (OR,0.60; 95% CI, 0.38–0.95; P = 0.030). In the subgroup with a low level of physical activity, UCP3−55CC carriers had higher BMI values than UCP3−55T carriers (16.6 ± 2.3 kg/m2 vs. 16.1 ± 1.9 kg/m2, P = 0.016). Low physical activity may aggravate the susceptibility to overweight in UCP2−866GG and UCP3−55CC carriers.Obesity (2009) 17 2, 355–362. doi:10.1038/oby.2008.531 [ABSTRACT FROM AUTHOR]

OBJECTIVES: To relate diabetes mellitus (DM) status and duration to late-life cognitive impairment and decline in men and women. DESIGN: Prospective cohort. SETTING: Community. PARTICIPANTS: Five thousand nine hundred seven men in the Physicians' Health Study II and 6,326 women in the Women's Health Study (mean age 74.1 and 71.9, respectively, at baseline cognitive assessment); 553 men and 405 women had DM. MEASUREMENTS: Primary outcomes were general cognition (the Telephone Interview for Cognitive Status (TICS) and a global score averaging five tests) and verbal memory. All participants had second assessments approximately 2 years later; women had third assessments an average of 4 years later. RESULTS: In adjusted linear regression models, participants with DM had significantly lower baseline scores for all outcomes, and longer duration of DM was associated with lower scores ( P-trends <.001). Men with DM had significantly greater 2-year cognitive decline than men without DM, and longer duration of DM was associated with worse decline ( P-trends ≤.01). In repeated-measures analyses of response profiles, women with DM had significantly greater 4-year cognitive decline in all outcomes than women without DM. In women, as in men, there was generally greater cognitive decline with longer duration of DM (e.g., the adjusted mean difference in decline on the TICS associated with duration of ≥5 years was −0.74 (95% confidence interval=−1.05 to −0.43) points ( P-trend <.001). There were no significant sex–DM interactions. CONCLUSION: Type 2 DM and longer duration of DM are similarly related to cognitive impairment and decline in men and women. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Cancer risk factors are more common among sexual minority populations (e.g., lesbian, bisexual) than their heterosexual peers, yet little is known about cancer incidence across sexual orientation groups.The 1989–2017 data from the Nurses’ Health Study II, a longitudinal cohort of female nurses across the United States, were analyzed (N = 101,543). Sexual orientation‐related cancer disparities were quantified by comparing any cancer incidence among four sexual minority groups based on self‐disclosure—(1) heterosexual with past same‐sex attractions/partners/identity; (2) mostly heterosexual; (3) bisexual; and (4) lesbian women—to completely heterosexual women using age‐adjusted incidence rate ratios (aIRR) calculated by the Mantel‐Haenszel method. Additionally, subanalyses at 21 cancer disease sites (e.g., breast, colon/rectum) were conducted.For all‐cancer analyses, there were no statistically significant differences in cancer incidence at the 5% type I error cutoff among sexual minority groups when compared to completely heterosexual women; the aIRR was 1.17 (95% CI,0.99–1.38) among lesbian women and 0.80 (0.58–1.10) among bisexual women. For the site‐specific analyses, incidences at multiple sites were significantly higher among lesbian women compared to completely heterosexual women: thyroid cancer (aIRR, 1.87 [1.03–3.41]), basal cell carcinoma (aIRR, 1.85 [1.09–3.14]), and non‐Hodgkin lymphoma (aIRR, 2.13 [1.10–4.12]).Lesbian women may be disproportionately burdened by cancer relative to their heterosexual peers. Sexual minority populations must be explicitly included in cancer prevention efforts. Comprehensive and standardized sexual orientation data must be systematically collected so nuanced sexual orientation‐related cancer disparities can be accurately assessed for both common and rare cancers. [ABSTRACT FROM AUTHOR]