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Background:The potential of an increased risk of breast cancer in women with diabetes has been the subject of a great deal of recent research.Methods:A meta-analysis was undertaken using a random effects model to investigate the association between diabetes and breast cancer risk.Results:Thirty-nine independent risk estimates were available from observational epidemiological studies. The summary relative risk (SRR) for breast cancer in women with diabetes was 1.27 (95% confidence interval (CI), 1.16–1.39) with no evidence of publication bias. Prospective studies showed a lower risk (SRR 1.23 (95% CI, 1.12–1.35)) than retrospective studies (SRR 1.36 (95% CI, 1.13–1.63)). Type 1 diabetes, or diabetes in pre-menopausal women, were not associated with risk of breast cancer (SRR 1.00 (95% CI, 0.74–1.35) and SRR 0.86 (95% CI, 0.66–1.12), respectively). Studies adjusting for body mass index (BMI) showed lower estimates (SRR 1.16 (95% CI, 1.08–1.24)) as compared with those studies that were not adjusted for BMI (SRR 1.33 (95% CI, 1.18–1.51)).Conclusion:The risk of breast cancer in women with type 2 diabetes is increased by 27%, a figure that decreased to 16% after adjustment for BMI. No increased risk was seen for women at pre-menopausal ages or with type 1 diabetes.

Childhood growth is of interest in medical research concerned with determinants and consequences of variation from healthy growth and development. Linear spline multilevel modelling is a useful approach for deriving individual summary measures of growth, which overcomes several data issues (co-linearity of repeat measures, the requirement for all individuals to be measured at the same ages and bias due to missing data). Here, we outline the application of this methodology to model individual trajectories of length/height and weight, drawing on examples from five cohorts from different generations and different geographical regions with varying levels of economic development. We describe the unique features of the data within each cohort that have implications for the application of linear spline multilevel models, for example, differences in the density and inter-individual variation in measurement occasions, and multiple sources of measurement with varying measurement error. After providing example Stata syntax and a suggested workflow for the implementation of linear spline multilevel models, we conclude with a discussion of the advantages and disadvantages of the linear spline approach compared with other growth modelling methods such as fractional polynomials, more complex spline functions and other non-linear models.

BackgroundThe current study explored the association between green space and depression in a deprived, multiethnic sample of pregnant women, and examined moderating and mediating variables.Method7547 women recruited to the ‘Born in Bradford’ cohort completed a questionnaire during pregnancy. A binary measure of depressive symptoms was calculated using a validated survey. Two green space measures were used: quintiles of residential greenness calculated using the normalised difference vegetation index for three neighbourhood sizes (100, 300 and 500 m buffer zones around participant addresses); access to major green spaces estimated as straight line distance between participant address and nearest green space (>0.5 hectares). Logistic regression analyses examined relationships between green space and depressive symptoms, controlling for ethnicity, demographics, socioeconomic status (SES) and health behaviours. Multiplicative interactions explored variations by ethnic group, SES or activity levels. Mediation analysis assessed indirect effects via physical activity.ResultsPregnant women in the greener quintiles were 18–23% less likely to report depressive symptoms than those in the least green quintile (for within 100 m of green space buffer zone). The green space-depressive symptoms association was significant for women with lower education or who were active. Physical activity partially mediated the association of green space, but explained only a small portion of the direct effect.ConclusionsHigher residential greenness was associated with a reduced likelihood of depressive symptoms. Associations may be stronger for more disadvantaged groups and for those who are already physically active. Improving green space is a promising intervention to reduce risk of depression in disadvantaged groups.

Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome.Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project.Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures.Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.Citation: Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P, Thomsen C, Wright J, Athersuch TJ, Avellana N, Basagaña X, Brochot C, Bucchini L, Bustamante M, Carracedo A, Casas M, Estivill X, Fairley L, van Gent D, Gonzalez JR, Granum B, Gražulevičienė R, Gutzkow KB, Julvez J, Keun HC, Kogevinas M, McEachan RR, Meltzer HM, Sabidó E, Schwarze PE, Siroux V, Sunyer J, Want EJ, Zeman F, Nieuwenhuijsen MJ. 2014. The Human Early-Life Exposome (HELIX): project rationale and design. Environ Health Perspect 122:535–544; http://dx.doi.org/10.1289/ehp.1307204

Over the study period the use of APE decreased but statistically significant variation was observed in its application independently of case mix. Reducing this variation will remove inequalities, reduce colostomy rates, and improve outcomes in rectal cancer. Rates of APE use could be a national performance measure.

The rate of resection of liver metastases increased over the study period but varied significantly across the country. Patients who underwent liver resection had 5-year survival comparable to that of patients with stage III colorectal cancer.

SummaryBackgroundDiagnosis of gestational diabetes predicts risk of infants who are large for gestational age (LGA) and with high adiposity, which in turn aims to predict a future risk of obesity in the offspring. South Asian women have higher risk of gestational diabetes, lower risk of LGA, and on average give birth to infants with greater adiposity than do white European women. Whether the same diagnostic criteria for gestational diabetes should apply to both groups of women is unclear. We aimed to assess the association between maternal glucose and adverse perinatal outcomes to ascertain whether thresholds used to diagnose gestational diabetes should differ between south Asian and white British women. We also aimed to assess whether ethnic origin affected prevalence of gestational diabetes irrespective of criteria used.MethodsWe used data (including results of a 26–28 week gestation oral glucose tolerance test) of women from the Born in Bradford study, a prospective study that recruited women attending the antenatal clinic at the Bradford Royal Infirmary, UK, between 2007 and 2011 and who intended to give birth to their infant in that hospital. We studied the association between fasting and 2 h post-load glucose and three primary outcomes (LGA [defined as birthweight >90th percentile for gestational age], high infant adiposity [sum of skinfolds >90th percentile for gestational age], and caesarean section). We calculated adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) for a 1 SD increase in fasting and post-load glucose. We established fasting and post-load glucose thresholds that equated to an OR of 1·75 for LGA and high infant adiposity in each group of women to identify ethnic-specific criteria for diagnosis of gestational diabetes.FindingsOf 13 773 pregnancies, 3420 were excluded from analyses. Of 10 353 eligible pregnancies, 4088 women were white British, 5408 were south Asian, and 857 were of other ethnic origin. The adjusted ORs of LGA per 1 SD fasting glucose were 1·22 (95% CI 1·08–1·38) in white British women and 1·43 (1·23–1·67) in south Asian women (pinteraction with ethnicity = 0·39). Results for high infant adiposity were 1·35 (1·23–1·49) and 1·35 (1·18–1·54; pinteraction with ethnicity=0·98), and for caesarean section they were 1·06 (0·97–1·16) and 1·11 (1·02–1·20; pinteraction with ethnicity=0·47). Associations between post-load glucose and the three primary outcomes were weaker than for fasting glucose. A fasting glucose concentration of 5·4 mmol/L or a 2 h post-load level of 7·5 mmol/L identified white British women with 75% or higher relative risk of LGA or high infant adiposity; in south Asian women, the cutoffs were 5·2 mmol/L or 7·2 mml/L; in the whole cohort, the cutoffs were 5·3 mmol/L or 7·5 mml/L. The prevalence of gestational diabetes in our cohort ranged from 1·2% to 8·7% in white British women and 4% to 24% in south Asian women using six different criteria. Compared with the application of our whole-cohort criteria, use of our ethnic-specific criteria increased th...