Beta-blocker usage and breast cancer survival: a nested case-control study within a UK clinical practice research datalink cohort.

Background: To investigate the association between post-diagnostic beta-blocker usage and risk of cancer-specific mortality in a large population-based cohort of female breast cancer patients.

Methods: A nested case-control study was conducted within a cohort of breast cancer patients identified from cancer registries in England(using the National Cancer Data repository) and diagnosed between 1998 and 2007. Patients who had a breast cancer-specific death(ascertained from Office of National Statistics death registration data) were each matched to four alive controls by year and age at diagnosis. Prescription data for these patients were available through the Clinical Practice Research Datalink. Conditional logistic regression models were used to investigate the association between breast cancer-specific death and beta-blocker usage.

Results: Post-diagnostic use of beta-blockers was identified in 18.9% of 1435 breast cancer-specific deaths and 19.4% of their 5697 matched controls,indicating little evidence of association between beta-blocker use and breast cancer-specific mortality [odds ratio (OR) = 0.97,95% confidence interval (CI) 0.83, 1.13]. There was also little evidence of an association when analyses were restricted to cardio non-selective beta-blockers (OR = 0.90, 95% CI 0.69, 1.17). Similar results were observed in analyses of drug dosage frequency and duration, and beta-blocker type.

Conclusions: In this large UK population-based cohort of breast cancer patients,there was little evidence of an association between post-diagnostic beta-blocker usage and breast cancer progression. Further studies which include information on tumour receptor status are warranted to determine whether response to beta-blockers varies by tumour subtypes.

Beta-blocker usage and prostate cancer survival:A nested case-control study in the UK Clinical Practice Research Datalink cohort

Background: Recent laboratory and epidemiological evidence suggests that beta-blockers could inhibit prostate cancer progression. Methods: We investigated the effect of beta-blockers on prostate cancer-specific mortality in a cohort of prostate cancer patients. Prostate cancer patients diagnosed between 1998 and 2006 were identified from the UK Clinical Practice Research Database and confirmed by cancer registries. Patients were followed up to 2011 with deaths identified by the Office of National Statistics. A nested case-control analysis compared patients dying from prostate cancer (cases) with up to three controls alive at the time of their death, matched by age and year of diagnosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Post-diagnostic beta-blocker use was identified in 25% of 1184 prostate cancer-specific deaths and 26% of 3531 matched controls. There was little evidence (P=0.40) of a reduction in the risk of cancer-specific death in beta-blocker users compared with non-users (OR=0.94 95% CI 0.81, 1.09). Similar results were observed after adjustments for confounders, in analyses by beta-blocker frequency, duration, type and for all-cause mortality. Conclusions: Beta-blocker usage after diagnosis was not associated with cancer-specific or all-cause mortality in prostate cancer patients in this large UK study.

Physical activity, sedentary behaviour and fetal macrosomia in uncomplicated pregnancies: A prospective cohort study

Objective: to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia.

Methods: a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing Z4000 g (study group) or o4000 g (control group). Women were recruited in a 1:1 ratio from antenatal clinics in Northern Ireland. Women wore a SenseWears Body Media Pro3 physical activity armband and completed a food diary for four consecutive days in the third trimester. Physical activity was measured in Metabolic Equivalent of Tasks (METs) where 1 MET¼1 kcal per kilogram of body weight per hour. Analysis of covariance (ANCOVA) was employed using the General Linear Model to adjust for potential confounders.

Findings: of the 112 women recruited, 100 complete datasets were available for analysis. There was no significant difference in energy balance between the two groups. Intensity of free living physical activity (average METs) of women predicted to deliver macrosomic infants (n¼50) was significantly lower than that of women in the control group (n¼50) (1.3 (0.2) METs (mean, standard deviation) versus 1.2 (0.2) METs; difference in means 0.1 METs (95% confidence interval: 0.19, 0.01); p¼0.021). Women predicted to deliver macrosomic infants also spent significantly more time in sedentary behaviour (r1 MET) than the control group (16.1 (2.8) hours versus 13.8 (4.3) hours; 2.0 hours (0.3, 3.7), p¼0.020).

Key conclusions and implications for practice: although there was no association between predicted fetal macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks.

Is a single item stress measure independently associated with subsequent severe injury: a prospective cohort study of 16,385 forest industry employees

Background: A previous review showed that high stress increases the risk of occupational injury by three- to five-fold. However, most of the prior studies have relied on short follow-ups. In this prospective cohort study we examined the effect of stress on recorded hospitalised injuries in an 8-year follow-up.
Methods: A total of 16,385 employees of a Finnish forest company responded to the questionnaire. Perceived stress was measured with a validated single-item measure, and analysed in relation recorded hospitalised injuries from 1986 to 2008. We used Cox proportional hazard regression models to examine the prospective associations between work stress, injuries and confounding factors.
Results: Highly stressed participants were approximately 40% more likely to be hospitalised due to injury over the follow-up period than participants with low stress. This association remained significant after adjustment for age, gender, marital status, occupational status, educational level, and physical work environment.
Conclusions: High stress is associated with an increased risk of severe injury.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States

Objective: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences.

Design: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US.

Setting: General population.

Participants: 26 018 men and women aged 50-79 years

Main outcome measures: All-cause, cardiovascular, and cancer mortality.

Results: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses.

Conclusions: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

Drivers of inequality in disability-free expectancy at birth and age 85 across space and time in Great Britain

Background: Although mortality and health inequalities at birth have increased both geographically and in socioeconomic terms, little is known about inequalities at age 85, the fastest growing sector of the population in Great Britain (GB).

Aim: To determine whether trends and drivers of inequalities in life expectancy (LE) and disability-free life expectancy (DFLE) at age 85 between 1991 and 2001 are the same as those at birth.

Methods: DFLE at birth and age 85 for 1991 and 2001 by gender were calculated for each local authority in GB using the Sullivan method. Regression modelling was used to identify area characteristics (rurality, deprivation, social class composition, ethnicity, unemployment, retirement migration) that could explain inequalities in LE and DFLE.

Results: Similar to values at birth, LE and DFLE at age 85 both increased between 1991 and 2001 (though DFLE increased less than LE) and gaps across local areas widened (and more for DFLE than LE). The significantly greater increases in LE and DFLE at birth for less-deprived compared with more-deprived areas were still partly present at age 85. Considering all factors, inequalities in DFLE at birth were largely driven by social class composition and unemployment rate, but these associations appear to be less influential at age 85.

Conclusions: Inequalities between areas in LE and DFLE at birth and age 85 have increased over time though factors explaining inequalities at birth (mainly social class and unemployment rates) appear less important for inequalities at age 85.

Post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific survival: a nested case-control study in a breast cancer cohort from the UK Clinical Practice Research Datalink

INTRODUCTION: Recent observational studies indicate that post-diagnostic use of aspirin in breast cancer patients may protect against cancer progression perhaps by inhibiting cyclooxygenase-2 dependent mechanisms. Evidence also supports a crucial role for interactions between tumour cells and circulating platelets in cancer growth and dissemination, therefore, use of low-dose aspirin may reduce the risk of death from cancer in breast cancer patients.

METHODS: A cohort of newly diagnosed breast cancer patients (1998 to 2006) were identified in the UK Clinical Practice Research Datalink (and confirmed by cancer registry linkage). Cancer-specific deaths were identified up to 2011 from Office for National Statistics mortality data. A nested case-control analysis was conducted using conditional logistic regression to compare post-diagnostic aspirin exposure using General Practice prescription data in 1,435 cases (breast cancer deaths) with 5,697 controls (matched by age and year of diagnosis).

RESULTS: After breast cancer diagnosis, 18.3% of cancer-specific deaths and 18.5% of matched controls received at least one prescription for low-dose aspirin, corresponding to an odds ratio (OR) of 0.98 (95% CI 0.83, 1.15). Adjustment for potential confounders (including stage and grade) had little impact on this estimate. No dose response relationship was observed when the number of tablets was investigated and no associations were seen when analyses were stratified by receipt of prescriptions for aspirin in the pre-diagnostic period, by stage at diagnosis or by receipt of prescriptions for hormone therapy.

CONCLUSIONS: Overall, in this large population-based cohort of breast cancer patients, there was little evidence of an association between receipt of post-diagnostic prescriptions for low-dose aspirin and breast cancer-specific death. However, information was not available on medication compliance or over-the-counter use of aspirin, which may have contributed to the null findings.

Women’s Perceptions and Experiences of Fetal Macrosomia

Objective
to explore women's perceptions and experiences of pregnancy and childbirth following birth of a macrosomic infant (birth weight ≥4000 g).

Methods
a qualitative design utilising interviews conducted 13–19 weeks post partum in women's homes. The study was conducted in one Health and Social Care Trust in Northern Ireland between January and September 2010. Participants were identified from a larger cohort of women recruited to a prospective study exploring the impact of physical activity and nutrition on macrosomia. Eleven women who delivered macrosomic infants participated in this phase of the study.

Findings
four overarching themes emerged: preparation for delivery; physical and emotional impact of macrosomia; professional relations and perceptions of macrosomia. Findings highlighted the importance of communication with health professionals in relation to both prediction of macrosomia and decision making about childbirth, and offers further understanding into the physical and emotional impact of having a macrosomic infant on women. Furthermore, there was evidence that beliefs and perceptions relating to macrosomia may influence birth experiences and uptake of health promotion messages.

Key conclusions and implications for practice
this study provides important insight into women's experiences of macrosomia throughout the perinatal period and how they were influenced by previous birth experiences, professional relations and personal perceptions and beliefs about macrosomia. Pregnant women at risk of having a macrosomic infant may require extra support throughout the antenatal period continuing into the postnatal period. Support needs to be tailored to the woman's information needs, with time allocated to explore previous birth experiences, beliefs about macrosomia and options for childbirth.

Anthropometric within-country Inequality and the Estimation of Skill Premia with Anthropometric Indicators

Recently, a method to measure inequality has been proposed that is based on an- thropometric indicators. Baten (1999, 2000) argued that the coefficient of variation of human stature (henceforth ‘CV’) is correlated with overall inequality in a society, and that it can be used as indicator, especially where income inequality measures are lack- ing. This correlation has been confirmed in further analyses, for example by Pradhan et al. (2003), Moradi and Baten (2005), Sunder (2003), Guntupalli and Baten (2006), Blum (2010a), van Zanden et al. (2010), see also Figure 1 and Table 1. The idea is that average height reflects nutritional conditions during early childhood and youth. Since wealthier people have better access to food, shelter and medical resources, they tend to be taller than the poorer part of the population. Hence, the variation of height of a cer- tain cohort may be indicative of income distribution during the decade of their birth. The aim of this study is firstly to provide an overview of different forms of within- country height inequality. Previous studies on the aspects of height inequality are re- viewed. Inequalities between ethnic groups, gender, inhabitants of different regions and income groups are discussed. In the two final sections, we compare height CVs of anthropological inequality with another indicator of inequality, namely skill premia. We also present estimates of skill premia for a set of countries and decades for which “height CVs”, as they will be called in the following, are available.

The DietCompLyf study: A prospective cohort study of breast cancer survival and phytoestrogen consumption

DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed.