Relationships between intensity, duration, cumulative dose, and timing of smoking with age at menopause: A pooled analysis of individual data from 17 observational studies.

BackgroundCigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.Methods and findingsA total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (ConclusionsThe probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause

The InterLACE study: Design, Data Harmonization and Characteristics Across 20 Studies on Women’s Health

Objectives: The International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) project is a global research collaboration that aims to advance understanding of women’s reproductive health in relation to chronic disease risk by pooling individual participant data from several cohort and cross-sectional studies. The aim of this paper is to describe the characteristics of contributing studies and to present the distribution of demographic and reproductive factors and chronic disease outcomes in InterLACE. Study design: InterLACE is an individual-level pooled study of 20 observational studies (12 of which are longitudinal) from ten countries. Variables were harmonized across studies to create a new and systematic synthesis of life-course data. Main outcome measures: Harmonized data were derived in three domains: 1) socio-demographic and lifestyle factors, 2) female reproductive characteristics, and 3) chronic disease outcomes (cardiovascular disease (CVD) and diabetes). Results: InterLACE pooled data from 229,054 mid-aged women. Overall, 76% of the women were Caucasian and 22% Japanese; other ethnicities (of 300 or more participants) included Hispanic/Latin American (0.2%), Chinese (0.2%), Middle Eastern (0.3%), African/black (0.5%), and Other (1.0%). The median age at baseline was 47 years (Inter-quartile range (IQR): 41–53), and that at the last follow-up was 56 years (IQR: 48–64). Regarding reproductive characteristics, half of the women (49.8%) had their first menstruation (menarche) at 12–13 years of age. The distribution of menopausal status and the prevalence of chronic disease varied considerably among studies. At baseline, most women (57%) were pre- or peri-menopausal, 20% reported a natural menopause (range 0.8–55.6%) and the remainder had surgery or were taking hormones. By the end of follow-up, the prevalence rates of CVD and diabetes were 7.2% (range 0.9–24.6%) and 5.1% (range 1.3–13.2%), respectively. Conclusions: The scale and heterogeneity of InterLACE data provide an opportunity to strengthen evidence concerning the relationships between reproductive health through life and subsequent risks of chronic disease, including cross-cultural comparisons

Does dog-ownership influence seasonal patterns of neighbourhood-based walking among adults? A longitudinal study

<p>Abstract</p> <p>Background</p> <p>In general dog-owners are more physically active than non-owners, however; it is not known whether dog-ownership can influence seasonal fluctuations in physical activity. This study examines whether dog-ownership influences summer and winter patterns of neighbourhood-based walking among adults living in Calgary, Canada.</p> <p>Methods</p> <p>A cohort of adults, randomly sampled from the Calgary metropolitan area, completed postal surveys in winter and summer 2008. Both winter and summer versions of the survey included questions on dog-ownership, walking for recreation, and walking for transportation in residential neighbourhoods. <b>Participation </b>in neighbourhood-based walking was compared, among dog-owners and non-owners, and in summer and winter, using general linear modeling. <b>Stability </b>of participation in neighbourhood-based walking across summer and winter among dog-owners and non-owners was also assessed, using logistic regression.</p> <p>Results</p> <p>A total of 428 participants participated in the study, of whom 115 indicated owning dogs at the time of both surveys. Dog-owners reported more walking for recreation in their neighbourhoods than did non-owners, both in summer and in winter. Dog-owners were also more likely than non-owners to report participation in walking for recreation in their neighbourhoods, in summer as well as in winter. Dog-owners and non-owners did not differ in the amount of walking that they reported for transportation, either in summer or in winter.</p> <p>Conclusions</p> <p>By acting as cues for physical activity, dogs may help their owners remain active across seasons. Policies and programs related to dog-ownership and dog-walking, such as dog-supportive housing and dog-supportive parks, may assist in enhancing population health by promoting physical activity.</p

Compositional analysis of bacterial communities in seawater, sediment, and sponges in the Misool coral reef system, Indonesia

Sponge species have been deemed high microbial abundance (HMA) or low microbial abundance (LMA) based on the composition and abundance of their microbial symbionts. In the present study, we evaluated the richness and composition of bacterial communities associated with one HMA sponge (Xestospongia testudinaria; Demospongiae: Haplosclerida: Petrosiidae), one LMA sponge (Stylissa carteri; Demospongiae: Scopalinida - Scopalinidae), and one sponge with a hitherto unknown microbial community (Aaptos suberitoides; Demospongiae: Suberitida: Suberitidae) inhabiting the Misool coral reef system in the West Papua province of Indonesia. The bacterial communities of these sponge species were also compared with seawater and sediment bacterial communities from the same coastal coral reef habitat. Using a 16S rRNA gene barcoded pyrosequencing approach, we showed that the most abundant phylum overall was Proteobacteria. The biotope (sponge species, sediment or seawater) explained almost 84% of the variation in bacterial composition with highly significant differences in composition among biotopes and a clear separation between bacterial communities from seawater and S. carteri; X. testudinaria and A. suberitoides and sediment. The Chloroflexi classes SAR202 and Anaerolineae were most abundant in A. suberitoides and X. testudinaria and both of these species shared several OTUs that were largely absent in the remaining biotopes. This suggests that A. suberitoides is a HMA sponge. Although similar, the bacterial communities of S. carteri and seawater were compositionally distinct. These results confirm compositional differences between sponge and non-sponge biotopes and between HMA and LMA sponges.publishe

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Dietary patterns and risk of breast cancer

Background: Evidence is emerging that prudent/healthy dietary patterns might be associated with a reduced risk of breast cancer. Methods: Using data from the prospective Melbourne Collaborative Cohort Study, we applied principal factor analysis to 124 foods and beverages to identify dietary patterns and estimated their association with breast cancer risk overall and by tumour characteristics using Cox regression. Results: During an average of 14.1 years of follow-up of 20 967 women participants, 815 invasive breast cancers were diagnosed. Among the four dietary factors that we identified, only that characterised by high consumption of fruit and salad was associated with a reduced risk, with stronger associations observed for tumours not expressing oestrogen (ER) and progesterone receptors (PR). Compared with women in the lowest quintile of the factor score, the hazard ratio for women in the highest quintile was 0.92 (95% confidence interval (CI)=0.70-1.21; test for trend, P=0.5) for ER-positive or PR-positive tumours and 0.48 (95% CI=0.26-0.86; test for trend, P=0.002) for ER-negative and PR-negative tumours (test for homogeneity, P=0.01). Conclusion: Our study provides additional support for the hypothesis that a dietary pattern rich in fruit and salad might protect against invasive breast cancer and that the effect might be stronger for ER- and PR-negative tumours. © 2011 Cancer Research UK All rights reserved

Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients

Canadian Institutes of Health Research, Grant/ Award Number: 81274; Huntsman Cancer Institute Pilot Funds; Leukemia Lymphoma Society, Grant/Award Number: 6067-09; the National Institute of Health/National Cancer Institute, Grant/Award Numbers: P30 CA016672, P30 CA042014, P30 CA13148, P50 CA186781, R01 CA107476, R01 CA134674, R01 CA168762, R01 CA186646, R01 CA235026, R21 CA155951, R25 CA092049, R25 CA47888, U54 CA118948; Utah Population Database, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah State Department of Health, University of Utah; VicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414; Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer Database; Mayo Clinic Cancer Center; University of Pisa and DKFZThe authors thank all site investigators that contributed to the studies within the Multiple Myeloma Working Group (Interlymph Consortium), staff involved at each site and, most importantly, the study participants for their contributions that made our study possible. This work was partially supported by intramural funds of University of Pisa and DKFZ. This work was supported in part by the National Institute of Health/National Cancer Institute (R25 CA092049, P30 CA016672, R01 CA134674, P30 CA042014, R01 CA186646, R21 CA155951, U54 CA118948, P30 CA13148, R25 CA47888, R01 CA235026, R01 CA107476, R01 CA168762, P50 CA186781 and the NCI Intramural Research Program), Leukemia Lymphoma Society (6067-09), Huntsman Cancer Institute Pilot Funds, Utah PopulationDatabase, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah StateDepartment of Health, University of Utah, Canadian Institutes of Health Research (Grant number 81274), VicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council (Grants 209057, 396414, 1074383), Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer Database and the Mayo Clinic Cancer Center.Open Access funding enabled and organized by ProjektDEAL.The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome. Using the genotype-tissue expression portal, we identified a total of 16 candidate genes with at least one eQTL SNP associated with their expression with P < 10(-7) either in EBV-transformed B-lymphocytes or whole blood. We genotyped the resulting 22 SNPs in 1327 MM cases from the International Multiple Myeloma rESEarch (IMMEnSE) consortium and examined their association with overall survival (OS) and progression-free survival (PFS), adjusting for age, sex, country of origin and disease stage. Three polymorphisms in two genes (TBRG4-rs1992292, TBRG4-rs2287535 and ENTPD1-rs2153913) showed associations with OS at P < .05, with the former two also associated with PFS. The associations of two polymorphisms in TBRG4 with OS were replicated in 1277 MM cases from the International Lymphoma Epidemiology (InterLymph) Consortium. A meta-analysis of the data from IMMEnSE and InterLymph (2579 cases) showed that TBRG4-rs1992292 is associated with OS (hazard ratio = 1.14, 95% confidence interval 1.04-1.26, P = .007). In conclusion, we found biologically a plausible association between a SNP in TBRG4 and OS of MM patients.Canadian Institutes of Health Research (CIHR) 81274Huntsman Cancer Institute Pilot FundsLeukemia and Lymphoma Society 6067-09United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Cancer Institute (NCI) P30 CA016672 P30 CA042014 P30 CA13148 P50 CA186781 R01 CA107476 R01 CA134674 R01 CA168762 R01 CA186646 R01 CA235026 R21 CA155951 R25 CA092049 R25 CA47888 U54 CA118948Utah Population Database, Utah Cancer Registry, Huntsman Cancer Center Support Grant, Utah State Department of Health, University of UtahVicHealth, Cancer Council Victoria, Australian National Health and Medical Research Council 1074383 209057 396414Victorian Cancer Registry, Australian Institute of Health and Welfare, Australian National Death Index, Australian Cancer DatabaseMayo Clinic Cancer CenterUniversity of PisaHelmholtz Associatio

Mammographic density and ageing:A collaborative pooled analysis of cross-sectional data from 22 countries worldwide

BACKGROUND: Mammographic density (MD) is one of the strongest breast cancer risk factors. Its age-related characteristics have been studied in women in western countries, but whether these associations apply to women worldwide is not known. METHODS AND FINDINGS: We examined cross-sectional differences in MD by age and menopausal status in over 11,000 breast-cancer-free women aged 35-85 years, from 40 ethnicity- and location-specific population groups across 22 countries in the International Consortium on Mammographic Density (ICMD). MD was read centrally using a quantitative method (Cumulus) and its square-root metrics were analysed using meta-analysis of group-level estimates and linear regression models of pooled data, adjusted for body mass index, reproductive factors, mammogram view, image type, and reader. In all, 4,534 women were premenopausal, and 6,481 postmenopausal, at the time of mammography. A large age-adjusted difference in percent MD (PD) between post- and premenopausal women was apparent (-0.46 cm [95% CI: -0.53, -0.39]) and appeared greater in women with lower breast cancer risk profiles; variation across population groups due to heterogeneity (I2) was 16.5%. Among premenopausal women, the √PD difference per 10-year increase in age was -0.24 cm (95% CI: -0.34, -0.14; I2 = 30%), reflecting a compositional change (lower dense area and higher non-dense area, with no difference in breast area). In postmenopausal women, the corresponding difference in √PD (-0.38 cm [95% CI: -0.44, -0.33]; I2 = 30%) was additionally driven by increasing breast area. The study is limited by different mammography systems and its cross-sectional rather than longitudinal nature. CONCLUSIONS: Declines in MD with increasing age are present premenopausally, continue postmenopausally, and are most pronounced over the menopausal transition. These effects were highly consistent across diverse groups of women worldwide, suggesting that they result from an intrinsic biological, likely hormonal, mechanism common to women. If cumulative breast density is a key determinant of breast cancer risk, younger ages may be the more critical periods for lifestyle modifications aimed at breast density and breast cancer risk reduction

Validation of diabetes mellitus and hypertension diagnosis in computerized medical records in primary health care

<p>Abstract</p> <p>Background</p> <p>Computerized Clinical Records, which are incorporated in primary health care practice, have great potential for research. In order to use this information, data quality and reliability must be assessed to prevent compromising the validity of the results.</p> <p>The aim of this study is to validate the diagnosis of hypertension and diabetes mellitus in the computerized clinical records of primary health care, taking the diagnosis criteria established in the most prominently used clinical guidelines as the gold standard against which what measure the sensitivity, specificity, and determine the predictive values.</p> <p>The gold standard for diabetes mellitus was the diagnostic criteria established in 2003 American Diabetes Association Consensus Statement for diabetic subjects. The gold standard for hypertension was the diagnostic criteria established in the Joint National Committee published in 2003.</p> <p>Methods</p> <p>A cross-sectional multicentre validation study of diabetes mellitus and hypertension diagnoses in computerized clinical records of primary health care was carried out. Diagnostic criteria from the most prominently clinical practice guidelines were considered for standard reference.</p> <p>Sensitivity, specificity, positive and negative predictive values, and global agreement (with kappa index), were calculated. Results were shown overall and stratified by sex and age groups.</p> <p>Results</p> <p>The agreement for diabetes mellitus with the reference standard as determined by the guideline was almost perfect (κ = 0.990), with a sensitivity of 99.53%, a specificity of 99.49%, a positive predictive value of 91.23% and a negative predictive value of 99.98%.</p> <p>Hypertension diagnosis showed substantial agreement with the reference standard as determined by the guideline (κ = 0.778), the sensitivity was 85.22%, the specificity 96.95%, the positive predictive value 85.24%, and the negative predictive value was 96.95%. Sensitivity results were worse in patients who also had diabetes and in those aged 70 years or over.</p> <p>Conclusions</p> <p>Our results substantiate the validity of using diagnoses of diabetes and hypertension found within the computerized clinical records for epidemiologic studies.</p