Lesley Fairley

Surgical management and outcomes of colorectal cancer liver metastases

This population‐based study investigated the frequency of hepatic resections for colorectal cancer metastases across England and their outcome.

Unacceptable variation in abdominoperineal excision rates for rectal cancer: time to intervene?

Objective: To determine the variation in the rates of use of abdominoperineal excision (APE) by cancer network, hospital trust and surgeon across England between 1998 and 2004 and determine if any variation could be explained by differences in patient characteristics such as stage of disease, age, gender or socioeconomic deprivation. Design: Retrospective study of a population-based dataset comprised of cancer registry and hospital episode statistics data. Setting: All NHS providers of rectal cancer surgery within England. Patients: 31 223 patients diagnosed with rectal cancer and receiving a major abdominal procedure within the NHS in England between 1998 and 2004. Main outcome measure: Rates and odds of use of APE were determined in relation to patient case-mix and each patient’s managing surgeon, trust and cancer network. Results: The rate of use of APE decreased from 30.5% in 1998 to 23.0% in 2004. Males, the economically deprived and those managed by surgeons operating on fewer than seven rectal cancer cases per year were all significantly more likely to receive an APE. There were also significant variations in the odds of receiving an APE over time and between individual surgeons and hospital trusts independently of patient case-mix. Conclusions: 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.

Cohort Profile: The Born in Bradford multi-ethnic family cohort study

Bradford Institute for Health Research, Bradford Teaching Hospitals Foundation Trust, Bradford, UK, School of Health Studies, University of Bradford, Bradford, UK, Edinburgh Ethnicity and Health Research Group, Centre for Population Health Sciences, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK, School of Sport, Exercise and Health Sciences, Loughborough University, Leicestershire, UK, Medical Research Council Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK, Paediatric Epidemiology Group, Centre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, UK and Department of Health Sciences, University of York, York, UK

The Human Early-Life Exposome (HELIX): Project Rationale and Design

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

The future burden of cancer in England: incidence and numbers of new patients in 2020

We estimated the future cancer incidence rates and the future numbers of cancer cases in England up to 2020 using cancer registration data for 1974–2003, and the official population projections from ONS up to 2023. Data were analysed using an age-period-cohort model as developed for the Nordic countries. We predict that for all cancers combined there will be relatively little change in age-standardised incidence rates in 2020. The number of new cancer cases per year in England is, however, predicted to increase by 33%, from 224 000 in 2001 to 299 000 cases in 2020. This increase is mainly due to the anticipated effects of population growth and ageing; cancer patients in 2020 will be older than todays cancer population.

A 10-YEAR RETROSPECTIVE REVIEW OF A NONRANDOMIZED COHORT OF 458 PATIENTS UNDERGOING RADICAL RADIOTHERAPY OR CYSTECTOMY IN YORKSHIRE, UK

PURPOSE We have previously reported on the mortality, morbidity, and 5-year survival of 458 patients who underwent radical radiotherapy or surgery for invasive bladder cancer in Yorkshire from 1993 to 1996. We aim to present the 10-year outcomes of these patients and to reassess factors predicting survival. METHODS AND MATERIALS The Northern and Yorkshire Cancer Registry identified 458 patients whose cases were subjected to Kaplan-Meier all-cause survival analyses, and a retrospective casenote analysis was undertaken on 398 (87%) for univariate and multivariate Cox proportional hazards modeling. Additional proportional hazards regression modeling was used to assess the statistical significance of variables on overall survival. RESULTS The ratio of radiotherapy to cystectomy was 3:1. There was no significant difference in overall 10-year survival between those who underwent radiotherapy (22%) and radical cystectomy (24%). Univariate analyses suggested that female sex, performance status, hydronephrosis and clinical T stage, were associated with an inferior outcome at 10 years. Patient age, tumor grade, treatment delay, and caseload factors were not significant. Multivariate analysis models were created for 0-2 and 2-10 years after treatment. There were no significant differences in treatment for 0-2 years; however, after 2 years follow-up there was some evidence of increased survival for patients receiving surgery compared with radiotherapy (hazard ratio 0.66, 95% confidence interval: 0.44-1.01, p = 0.06). CONCLUSIONS a 10-year minimum follow-up has rarely been reported after radical treatment for invasive bladder cancer. At 10 years, there was no statistical difference in all-cause survival between surgery and radiotherapy treatment modalities.

Social class inequalities in perinatal outcomes: Scotland 1980–2000

Objective: To examine social class inequalities in adverse perinatal events in Scotland between 1980 and 2000 and how these were influenced by other maternal risk factors. Design: Population based study using routine maternity discharge data. Setting: Scotland. Participants: All women who gave birth to a live singleton baby in Scottish hospitals between 1980 and 2000 (n = 1 282 172). Main outcome measures: Low birth weight (LBW), preterm birth, and small for gestational age (SGA). Results: The distribution of social class changed over time, with the proportion of mothers with undetermined social class increasing from 3.9% in 1980–84 to 14.8% in 1995–2000. The relative index of inequality (RII) decreased during the 1980s for all outcomes. The RII then increased between the early and late 1990s (LBW from 2.09 (95%CI 1.97, 2.22) to 2.43 (2.29, 2.58), preterm from 1.52 (1.44, 1.61) to 1.75 (1.65, 1.86), and SGA from 2.28 (2.14, 2.42) to 2.49 (2.34, 2.66) respectively). Inequalities were greatest in married mothers, mothers aged over 35, mothers taller than 164 cm, and mothers with a parity of one or more. Inequalities were also greater by the end of the 1990s than at the start of the 1980s for women of parity one or more and for mothers who were not married. Conclusion: Despite decreasing during the 1980s, inequalities in adverse perinatal outcomes increased during the 1990s in all strata defined by maternal characteristics.

The association between green space and depressive symptoms in pregnant women: moderating roles of socioeconomic status and physical activity

Background The current study explored the association between green space and depression in a deprived, multiethnic sample of pregnant women, and examined moderating and mediating variables. Method 7547 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. Results Pregnant 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. Conclusions Higher 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.

Linear spline multilevel models for summarising childhood growth trajectories: A guide to their application using examples from five birth cohorts

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.

The influence of both individual and area based socioeconomic status on temporal trends in Caesarean sections in Scotland 1980-2000

BackgroundCaesarean section rates have risen over the last 20 years. Elective Caesarean section rates have been shown to be linked to area deprivation in England, women in the most deprived areas were less likely to have an elective section than those in the most affluent areas. We examine whether individual social class, area deprivation or both are related to Caesarean sections in Scotland and investigate changes over time.MethodsRoutine maternity discharge data from live singleton births in Scottish hospitals from three time periods were used; 1980-81 (n = 133,555), 1990-91 (n = 128,933) and 1999-2000 (n = 102,285). Multilevel logistic regression, with 3 levels (births, postcode sector and Health Board) was used to analyse emergency and elective Caesareans separately; analysis was further stratified by previous Caesarean section. The relative index of inequality (RII) was used to assess socioeconomic inequalities.ResultsBetween 1980-81 and 1999-2000 the emergency section rate increased from 6.3% to 11.9% and the elective rate from 3.6% to 5.5%. In 1980-81 and 1990-91 emergency Caesareans were more likely among women at the bottom of the social class hierarchy compared to those at the top (RII = 1.14, 95%CI 1.00-1.25 and RII = 1.13, 1.03-1.23 respectively) and also among women in the most deprived areas compared to those in the most affluent (RII = 1.18, 1.05-1.32 and RII = 1.13, 1.02-1.26 respectively). In 1999-2000 the odds of an elective section were lower for women at the bottom of the social class hierarchy than those at the top (RII = 0.87, 0.76-1.00) and also lower in women in the most deprived areas compared to those in the most affluent (RII = 0.85, 0.73-0.99).ConclusionsBoth individual social class and area deprivation are independently associated with Caesarean sections in Scotland. The tendency for disadvantaged women to be more likely to receive emergency sections disappeared at the same time as the likelihood of advantaged groups receiving elective sections increased.