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1.  Long-term Adherence to Healthy Dietary Guidelines and Chronic Inflammation in the Prospective Whitehall II Study☆ 
The American Journal of Medicine  2015;128(2):152-160.e4.
Background
Inflammation plays an important role in the cause of cardiovascular diseases and may contribute to the association linking an unhealthy diet to chronic age-related diseases. However, to date the long-term associations between diet and inflammation have been poorly described. Our aim was to assess the extent to which adherence to a healthy diet and dietary improvements over a 6-year exposure period prevented subsequent chronic inflammation over a 5-year follow-up in a large British population of men and women.
Methods
Data were drawn from 4600 adults (mean ± standard deviation, age 49.6 ± 6.1 years, 28% were women) from the prospective Whitehall cohort II study. Adherence to a healthy diet was measured using Alternative Healthy Eating Index (AHEI) scores in 1991-1993 (50.7 ± 11.9 points) and 1997-1999 (51.6 ± 12.4 points). Chronic inflammation, defined as average levels of serum interleukin-6 from 2 measures 5 years apart, was assessed in 1997-1999 and 2002-2004.
Results
After adjustment for sociodemographic factors, health behaviors, and health status, participants who maintained a high AHEI score (ie, a healthy diet, n = 1736, 37.7%) and those who improved this score over time (n = 681, 14.8%) showed significantly lower mean levels of interleukin-6 (1.84 pg/mL, 95% confidence interval [CI], 1.71-1.98 and 1.84 pg/mL, 95% CI, 1.70-1.99, respectively) than those who had a low AHEI score (n = 1594, 34.6%) over the 6-year exposure period (2.01 pg/mL, 95% CI, 1.87-2.17).
Conclusions
These data suggest that maintaining and improving adherence to healthy dietary recommendations may reduce the risk of long-term inflammation.
doi:10.1016/j.amjmed.2014.10.002
PMCID: PMC4315808  PMID: 25305231
Alternative Healthy Eating Index; Diet quality indices; Inflammatory marker; Interleukin-6; Middle-aged population; Nutritional Epidemiology; Prospective cohort
2.  Weekday and weekend patterns of objectively measured sitting, standing, and stepping in a sample of office-based workers: the active buildings study 
BMC Public Health  2015;15:9.
Background
There is a growing body of research into the total amount and patterns of sitting, standing and stepping in office-based workers and few studies using objectively measured sitting and standing. Understanding these patterns may identify daily times opportune for interventions to displace sitting with activity.
Methods
A sample of office-based workers (n = 164) residing in England were fitted with thigh-worn ActivPal accelerometers and devices were worn 24 hours a day for five consecutive days, always including Saturday and Sunday and during bathing and sleeping. Daily amounts and patterns of time spent sitting, standing, stepping and step counts and frequency of sit/stand transitions, recorded by the ActivPal accelerometer, were reported.
Results
Total sitting/standing time was similar on weekdays (10.6/4.1 hrs) and weekends (10.6/4.3 hrs). Total step count was also similar over weekdays (9682 ± 3872) and weekends (9518 ± 4615). The highest physical activity levels during weekdays were accrued at 0700 to 0900, 1200 to 1400, and 1700 to 1900; and during the weekend at 1000 to 1700. During the weekday the greatest amount of sitting was accrued at 0900 to 1200, 1400 to 1700, and 2000 to 2300, and on the weekend between 1800 and 2300. During the weekday the greatest amount of standing was accrued between 0700 and 1000 and 1700 and 2100, and on the weekend between 1000 and 1800. On the weekday the highest number of sit/stand transitions occurred between 0800 to 0900 and remained consistently high until 1800. On the weekend, the highest number occurred between 1000 to 1400 and 1900 to 2000.
Conclusion
Office based-workers demonstrate high levels of sitting during both the working week and weekend. Interventions that target the working day and the evenings (weekday and weekend) to displace sitting with activity may offer most promise for reducing population levels of sedentary behaviour and increasing physical activity levels, in office-based workers residing in England.
doi:10.1186/s12889-014-1338-1
PMCID: PMC4308830  PMID: 25595219
Physical activity; Sitting; Standing; Patterns; Levels; Office workers
3.  Blunted glucocorticoid and mineralocorticoid sensitivity to stress in people with diabetes 
Psychoneuroendocrinology  2015;51:209-218.
Highlights
•Impaired stress responsivity in type 2 diabetes is associated with a lack of mineralocorticoid and glucocorticoid sensitivity.•Corticosteroid sensitivity in type 2 diabetes correlates to HbA1c.•Type 2 diabetes participants showed blunted response to stress in inflammatory cytokines.
Summary
Psychological stress may contribute to type 2 diabetes but mechanisms are still poorly understood. In this study, we examined whether stress responsiveness is associated with glucocorticoid and mineralocorticoid sensitivity in a controlled experimental comparison of people with type 2 diabetes and non-diabetic participants. Thirty-seven diabetes patients and 37 healthy controls underwent psychophysiological stress testing. Glucocorticoid (GR) and mineralocorticoid sensitivity (MR) sensitivity were measured by dexamethasone- and prednisolone-inhibition of lipopolysaccharide (LPS)-induced interleukin (IL) 6 levels, respectively. Blood pressure (BP) and heart rate were monitored continuously, and we periodically assessed salivary cortisol, plasma IL-6 and monocyte chemotactic protein (MCP-1). Following stress, both glucocorticoid and mineralocorticoid sensitivity decreased among healthy controls, but did not change in people with diabetes. There was a main effect of group on dexamethasone (F(1,74) = 6.852, p = 0.013) and prednisolone (F(1,74) = 7.295, p = 0.010) sensitivity following stress at 45 min after tasks. People with diabetes showed blunted stress responsivity in systolic BP, diastolic BP, heart rate, IL-6, MCP-1, and impaired post-stress recovery in heart rate. People with Diabetes had higher cortisol levels as measured by the total amount excreted over the day and increased glucocorticoid sensitivity at baseline. Our study suggests that impaired stress responsivity in type-2 diabetes is in part due to a lack of stress-induced changes in mineralocorticoid and glucocorticoid sensitivity.
doi:10.1016/j.psyneuen.2014.09.023
PMCID: PMC4275581  PMID: 25462894
HPA axis; Corticosteroid sensitivity; Acute stress; Cytokines; Auto-immune diseases; Cardiovascular
4.  Long working hours, socioeconomic status, and the risk of incident type 2 diabetes: a meta-analysis of published and unpublished data from 222 120 individuals 
Summary
Background
Working long hours might have adverse health effects, but whether this is true for all socioeconomic status groups is unclear. In this meta-analysis stratified by socioeconomic status, we investigated the role of long working hours as a risk factor for type 2 diabetes.
Methods
We identified four published studies through a systematic literature search of PubMed and Embase up to April 30, 2014. Study inclusion criteria were English-language publication; prospective design (cohort study); investigation of the effect of working hours or overtime work; incident diabetes as an outcome; and relative risks, odds ratios, or hazard ratios (HRs) with 95% CIs, or sufficient information to calculate these estimates. Additionally, we used unpublished individual-level data from 19 cohort studies from the Individual-Participant-Data Meta-analysis in Working-Populations Consortium and international open-access data archives. Effect estimates from published and unpublished data from 222 120 men and women from the USA, Europe, Japan, and Australia were pooled with random-effects meta-analysis.
Findings
During 1·7 million person-years at risk, 4963 individuals developed diabetes (incidence 29 per 10 000 person-years). The minimally adjusted summary risk ratio for long (≥55 h per week) compared with standard working hours (35–40 h) was 1·07 (95% CI 0·89–1·27, difference in incidence three cases per 10 000 person-years) with significant heterogeneity in study-specific estimates (I2=53%, p=0·0016). In an analysis stratified by socioeconomic status, the association between long working hours and diabetes was evident in the low socioeconomic status group (risk ratio 1·29, 95% CI 1·06–1·57, difference in incidence 13 per 10 000 person-years, I2=0%, p=0·4662), but was null in the high socioeconomic status group (1·00, 95% CI 0·80–1·25, incidence difference zero per 10 000 person-years, I2=15%, p=0·2464). The association in the low socioeconomic status group was robust to adjustment for age, sex, obesity, and physical activity, and remained after exclusion of shift workers.
Interpretation
In this meta-analysis, the link between longer working hours and type 2 diabetes was apparent only in individuals in the low socioeconomic status groups.
Funding
Medical Research Council, European Union New and Emerging Risks in Occupational Safety and Health research programme, Finnish Work Environment Fund, Swedish Research Council for Working Life and Social Research, German Social Accident Insurance, Danish National Research Centre for the Working Environment, Academy of Finland, Ministry of Social Affairs and Employment (Netherlands), Economic and Social Research Council, US National Institutes of Health, and British Heart Foundation.
doi:10.1016/S2213-8587(14)70178-0
PMCID: PMC4286814  PMID: 25262544
5.  Body mass index, waist circumference, and waist-hip ratio: which is the better discriminator of cardiovascular disease mortality risk? Evidence from an individual-participant meta-analysis of 82,864 participants from nine cohort studies 
Few studies have examined both the relative magnitude of association and the discriminative capability of multiple indicators of obesity with cardiovascular disease (CVD) mortality risk. We conducted an individual-participant meta-analysis of 9 cohort studies of men and women drawn from the British general population resulted in sample of 82,864 individuals. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were measured directly. There were 6,641 deaths (1,998 CVD) during a mean of 8.1 years of follow-up. After adjustment, a one SD higher in WHR and WC was related to a higher risk of CVD mortality (HR (95% CI)): 1.15 (1.05-1.25) and 1.15 (1.04-1.27), respectively. The risk of CVD also increased linearly across quintiles of both these abdominal obesity markers with a 66% increased risk in the highest quintile of WHR. In age- and sex-adjusted models only, BMI was related to CVD mortality but not in any other analyses. No major differences were revealed in the discrimination capabilities of models with BMI, WC or WHR for cardiovascular or total mortality outcomes. In conclusion, measures of abdominal adiposity, but not BMI, were related to an increased risk of cardiovascular disease mortality. No difference was observed in discrimination capacities between adiposity markers.
doi:10.1111/j.1467-789X.2011.00879.x
PMCID: PMC4170776  PMID: 21521449
body mass index; waist circumference; waist-to-hip ratio; cardiovascular disease mortality
6.  ‘On Your Feet to Earn Your Seat’, a habit-based intervention to reduce sedentary behaviour in older adults: study protocol for a randomized controlled trial 
Trials  2014;15(1):368.
Background
Many older adults are both highly sedentary (that is, spend considerable amounts of time sitting) and physically inactive (that is, do little physical activity). This protocol describes an exploratory trial of a theory-based behaviour change intervention in the form of a booklet outlining simple activities (‘tips’) designed both to reduce sedentary behaviour and to increase physical activity in older adults. The intervention is based on the ‘habit formation’ model, which proposes that consistent repetition leads to behaviour becoming automatic, sustaining activity gains over time.
Methods
The intervention is being developed iteratively, in line with Medical Research Council complex intervention guidelines. Selection of activity tips was informed by semi-structured interviews and focus groups with older adults, and input from a multidisciplinary expert panel. An ongoing preliminary field test of acceptability among 25 older adults will inform further refinement. An exploratory randomized controlled trial will be conducted within a primary care setting, comparing the tips booklet with a control fact sheet. Retired, inactive and sedentary adults (n = 120) aged 60 to 74 years, with no physical impairments precluding light physical activity, will be recruited from general practices in north London, UK. The primary outcomes are recruitment and attrition rates. Secondary outcomes are changes in behaviour, habit, health and wellbeing over 12 weeks.
Discussion
Data will be used to inform study procedures for a future, larger-scale definitive randomized controlled trial.
Trial registration
Current Controlled Trials ISRCTN47901994.
Electronic supplementary material
The online version of this article (doi:10.1186/1745-6215-15-368) contains supplementary material, which is available to authorized users.
doi:10.1186/1745-6215-15-368
PMCID: PMC4180306  PMID: 25240737
Sedentary behaviour; physical activity; behaviour change; habit; older adults
7.  Sociodemographic, behavioural and health factors associated with changes in older adults’ TV viewing over 2 years 
Background
Of all age groups, older adults spend the most time watching TV, which is one of the most common sedentary behaviours. Such sedentary activity in older adulthood is thought to risk deterioration of physical and mental functioning, health and wellbeing. Identifying the characteristics of older adults whose TV viewing increases over time may help to target sedentary behaviour reduction interventions to those in most urgent need. Yet, studies of the factors associated with TV viewing have predominantly been cross-sectional. This study used a prospective design to describe changes in TV viewing over a two-year follow-up period, and to model socio-demographic, behavioural and health factors associated with observed changes in viewing time.
Methods
A two-year follow-up of 6,090 male and female older adults (mean age 64.9 ± 8.9 years) was conducted in the English Longitudinal Study of Ageing, a cohort of community dwelling older adults. TV viewing time was self-reported at baseline and at follow-up. The sample was categorised according to baseline TV viewing duration (<2 hrs/d, 2 < 4 hrs/d, 4 < 6 hrs/d, ≥6 hrs/d), and the observed direction and extent of changes in viewing duration were described for each category. Socio-demographic, behavioural and health variables (socioeconomic status, depressive symptoms, disability, chronic illness, body mass index, physical activity, smoking), as measured at baseline, were entered into regression models as predictors of changes in TV viewing time between baseline and follow-up.
Results
Mean self-reported TV viewing time increased from 5.32 ± 4.08 hrs/d at baseline to 5.53 ± 4.19 hrs/d at follow-up (p < 0.001). Forty-nine per cent of participants increased their TV viewing (23% of all participants by 60 minutes or more), 41% decreased their viewing, and 10% reported no change in viewing duration. Increases in TV viewing at follow-up were associated with lower socioeconomic status, presence of depressive symptoms, higher BMI, physical inactivity, and being a smoker at baseline.
Conclusions
Findings call for the development of effective behaviour change interventions to counter increases in inactive TV viewing among older adults, and point to subgroups who may need to be prioritised for such interventions.
Electronic supplementary material
The online version of this article (doi:10.1186/s12966-014-0102-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12966-014-0102-3
PMCID: PMC4149242
Older adults; Sedentary behaviour; TV viewing; Screen time; Prospective
8.  Camden active spaces: Does the construction of active school playgrounds influence children's physical activity levels? A longitudinal quasi-experiment protocol 
BMJ Open  2014;4(8):e005729.
Introduction
Physical activity is essential for every facet of children's health. However, physical activity levels in British children are low. The school environment is a promising setting to increase children's physical activity but limited empirical evidence exists on how a change in the outdoor physical school environment influences physical activity behaviour. The London Borough of Camden is redesigning seven existing school playgrounds to engage children to become more physically active. The primary aim of this project is to evaluate the impact of the redesigned playgrounds on children's physical activity, well-being and physical function/fitness.
Method and analysis
This project will use a longitudinal quasi-experimental design. Seven experimental schools and one control school will take part. One baseline data collection session and two follow-ups will be carried out. Between baseline and follow-up, the experimental school playgrounds will be redesigned. At baseline, a series of fitness tests, anthropometric and questionnaire measurements, and 7-day objective physical activity monitoring (Actigraph accelerometer) will be carried out on children (aged 5–16 years). This will be repeated at follow-up. Changes in overall physical activity levels and levels during different times of the day (eg, school breaks) will be examined. Multilevel regression modelling will be used to analyse the data.
Ethics and dissemination
The results of this study will be disseminated through peer-review publications and scientific presentations. Ethical approval was obtained through the University College London Research Ethics Committee (Reference number: 4400/002).
doi:10.1136/bmjopen-2014-005729
PMCID: PMC4139631  PMID: 25232566
Preventive Medicine; Public Health; Sports Medicine
9.  Combined effect of physical activity and leisure time sitting on long-term risk of incident obesity and metabolic risk factor clustering 
Diabetologia  2014;57(10):2048-2056.
Aims/hypothesis
Our study aimed to investigate the combined effects of moderate-to-vigorous physical activity and leisure time sitting on the long-term risk of obesity and clustering of metabolic risk factors.
Methods
The duration of moderate and vigorous physical activity and of leisure time sitting was assessed by questionnaire between 1997 and 1999 among 3,670 participants from the Whitehall II cohort study (73% male; mean age 56 years). Multivariable-adjusted logistic regression models examined associations of physical activity and leisure time sitting tertiles with odds of incident obesity (BMI ≥ 30 kg/m2) and incident metabolic risk factor clustering (two or more of the following: low HDL-cholesterol, high triacylglycerol, hypertension, hyperglycaemia, insulin resistance) at 5 and 10 year follow-ups.
Results
Physical activity, but not leisure time sitting, was associated with incident obesity. The lowest odds of incident obesity after 5 years were observed for individuals reporting both high physical activity and low leisure time sitting (OR = 0.26; 95% CI 0.11, 0.64), with weaker effects after 10 years. Compared with individuals in the low physical activity/high leisure time sitting group, those with intermediate levels of both physical activity and leisure time sitting had lower odds of incident metabolic risk factor clustering after 5 years (OR 0.53; 95% CI 0.36, 0.78), with similar odds after 10 years.
Conclusions/interpretation
Both high levels of physical activity and low levels of leisure time sitting may be required to substantially reduce the risk of obesity. Associations with developing metabolic risk factor clustering were less clear.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-014-3323-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
doi:10.1007/s00125-014-3323-8
PMCID: PMC4153972  PMID: 25078481
Epidemiology; Exercise; Metabolic syndrome; Obesity; Weight regulation
10.  Objectively assessed physical activity, adiposity, and inflammatory markers in people with type 2 diabetes 
Objective
Inflammatory processes may play an important role in the development of acute coronary syndromes in people with type 2 diabetes; thus, strategies to control inflammation are of clinical importance. We examined the cross-sectional association between objectively assessed physical activity and inflammatory markers in a sample of people with type 2 diabetes.
Methods
Participants were 71 men and 41 women (mean age=63.9±7 years), without a history of cardiovascular disease, drawn from primary care clinics. Physical activity was objectively measured using waist-worn accelerometers (Actigraph GT3X) during waking hours for seven consecutive days.
Results
We observed inverse associations between moderate-to-vigorous physical activity (per 10 min) with plasma interleukin-6 (B=−0.035, 95% CI −0.056 to −0.015), interleukin-1ra (B=−0.033, 95% CI −0.051 to −0.015), and monocyte chemotactic protein-1 (B=−0.011, 95% CI −0.021 to 0.000). These associations largely persisted in multivariable adjusted models, although body mass index considerably attenuated the effect estimate.
Conclusions
These data demonstrate an inverse association between physical activity and inflammatory markers in people with type 2 diabetes.
doi:10.1136/bmjdrc-2014-000030
PMCID: PMC4212571  PMID: 25452870
Cytokine(s); Epidemiology; Type 2 Diabetes; Physical Activity and Health
11.  Metabolically healthy obesity: What is the role of sedentary behaviour?☆ 
Preventive Medicine  2014;62(100):35-37.
Objective
The role of sedentary behaviour in metabolically healthy obesity is unknown. We examined cross-sectional differences in television viewing time across metabolic and obesity phenotypes, hypothesizing that healthy obese individuals spend less time viewing television than their unhealthy counterparts.
Methods
A nationally representative sample of 4931 older adults in England (mean age 65.1; SD = 8.9 years) was drawn from the 2008/9 wave of the English Longitudinal Study of Ageing. Average weekly television viewing time was derived from two questions about weekday and weekend viewing. Obesity was defined as body mass index ≥ 30 kg/m2, and metabolically healthy as having < 2 metabolic abnormalities (low HDL-cholesterol, high triglycerides, high blood pressure, hyperglycaemia, high inflammation).
Results
After adjusting for covariates including chronic illness, functional limitations and physical activity, mean weekly viewing times were 4.7 (95% confidence interval 2.9, 6.5), 5.8 (2.5, 9.0) and 7.8 (5.7, 9.8) h higher in unhealthy non-obese, healthy obese, and unhealthy obese groups respectively, compared to the healthy non-obese group (p for heterogeneity < 0.001).
Conclusions
A common type of leisure-time sedentary behaviour varies across metabolic and obesity phenotypes. However, healthy obesity is not explained through differences in leisure-time sedentary behaviour.
doi:10.1016/j.ypmed.2014.01.028
PMCID: PMC3995089  PMID: 24513171
Sedentary behaviour; Television viewing; Obesity; Metabolic health
12.  Associations between objectively assessed and self-reported sedentary time with mental health in adults: an analysis of data from the Health Survey for England 
BMJ Open  2014;4(3):e004580.
Objective
There is increasing interest in the association between sedentary behaviour and mental health, although most studies have relied solely on self-reported measures, thus making results prone to various biases. The aim was to compare associations between objectively assessed and self-reported sedentary time with mental health in adults.
Setting
Community dwelling population sample drawn from the 2008 Health Survey for England.
Participants
11 658 (self-report analysis) and 1947 (objective data) men and women.
Primary outcome
The 12-item General Health Questionnaire was administered to assess psychological distress. Sedentary and physical activity (exposure) was objectively measured using accelerometers (Actigraph GT1M) worn around the waist during waking hours for seven consecutive days.
Results
The highest tertile of objective sedentary time was associated with higher risk of psychological distress (multivariate adjusted OR=1.74, 95% CI 1.07 to 2.83), as was the highest tertile of self-reported total sitting time (OR=1.34, 95% CI 1.15 to 1.56). Self-reported, but not objective, moderate-to-vigorous physical activity was associated with lower risk of psychological distress. Only objective light-intensity activity was associated with lower risk of psychological distress.
Conclusions
Sedentary time is associated with adverse mental health.
doi:10.1136/bmjopen-2013-004580
PMCID: PMC3963121  PMID: 24650807
Mental Health; Epidemiology; Public Health
13.  A non-exercise testing method for estimating cardiorespiratory fitness: associations with all-cause and cardiovascular mortality in a pooled analysis of eight population-based cohorts 
European Heart Journal  2012;34(10):750-758.
Aims
Cardiorespiratory fitness (CRF) is a key predictor of chronic disease, particularly cardiovascular disease (CVD), but its assessment usually requires exercise testing which is impractical and costly in most health-care settings. Non-exercise testing cardiorespiratory fitness (NET-F)-estimating methods are a less resource-demanding alternative, but their predictive capacity for CVD and total mortality has yet to be tested. The objective of this study is to examine the association of a validated NET-F algorithm with all-cause and CVD mortality.
Methods and results
The participants were 32 319 adults (14 650 men) aged 35–70 years who took part in eight Health Survey for England and Scottish Health Survey studies between 1994 and 2003. Non-exercise testing cardiorespiratory fitness (a metabolic equivalent of VO2max) was calculated using age, sex, body mass index (BMI), resting heart rate, and self-reported physical activity. We followed participants for mortality until 2008. Two thousand one hundred and sixty-five participants died (460 cardiovascular deaths) during a mean 9.0 [standard deviation (SD) = 3.6] year follow-up. After adjusting for potential confounders including diabetes, hypertension, smoking, social class, alcohol, and depression, a higher fitness score according to the NET-F was associated with a lower risk of mortality from all-causes (hazard ratio per SD increase in NET-F 0.85, 95% confidence interval: 0.78–0.93 in men; 0.88, 0.80–0.98 in women) and CVD (men: 0.75, 0.63–0.90; women: 0.73, 0.60–0.92). Non-exercise testing cardiorespiratory fitness had a better discriminative ability than any of its components (CVD mortality c-statistic: NET-F = 0.70–0.74; BMI = 0.45–0.59; physical activity = 0.60–0.64; resting heart rate = 0.57–0.61). The sensitivity of the NET-F algorithm to predict events occurring in the highest risk quintile was better for CVD (0.49 in both sexes) than all-cause mortality (0.44 and 0.40 for men and women, respectively). The specificity for all-cause and CVD mortality ranged between 0.80 and 0.82. The net reclassification improvement of CVD mortality risk (vs. a standardized aggregate score of the modifiable components of NET-F) was 27.2 and 21.0% for men and women, respectively.
Conclusion
The CRF-estimating method NET-F that does not involve exercise testing showed consistent associations with all-cause and cardiovascular mortality, and it had good discrimination and excellent risk reclassification improvement. As such, it merits further attention as a practical and potentially and useful risk prediction tool.
doi:10.1093/eurheartj/ehs097
PMCID: PMC3590456  PMID: 22555215
Epidemiology; Non-exercise testing; Cardiorespiratory fitness; Cardiovascular disease; Physical activity; Health Survey for England
14.  Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts 
F1000Research  2014;2:233.
Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.
 
Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.
 
Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
doi:10.12688/f1000research.2-233.v2
PMCID: PMC3938244  PMID: 24627793
15.  Physical activity and inflammatory markers over 10 years follow up in men and women from the Whitehall II cohort study 
Circulation  2012;126(8):928-933.
Background
Inflammatory processes are putative mechanisms underlying the cardio-protective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period.
Methods and Results
Participants were 4289 men and women (mean age 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 hours per week moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower CRP and IL6 levels and this difference remained stable over time. In comparison to participants that rarely adhered to physical activity guidelines over the 10 years follow-up, the high adherence group displayed lower logeCRP (β=−0.07, 95% CI, −0.12, −0.02) and logeIL-6 (β=−0.07, 95% CI, −0.10, −0.03) at follow up after adjustment for a range of covariates. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hours/wk displayed lower loge CRP (B coefficient =−0.05, 95% CI, −0.10, −0.001) and loge IL-6 (B coefficient =−0.06, 95% CI, −0.09, −0.03) at follow up.
Conclusions
Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the pro-inflammatory state seen with ageing.
doi:10.1161/CIRCULATIONAHA.112.103879
PMCID: PMC3890998  PMID: 22891048
Ageing; C-reactive protein; exercise; physical activity; inflammation
16.  Watching sport on television, physical activity, and risk of obesity in older adults 
BMC Public Health  2014;14:10.
Background
Television (TV) viewing has been associated with obesity although the effects of specific TV content on health and other behaviours remains unknown. We examined the association between watching sport on TV, physical activity levels, and risk of obesity.
Methods
We studied 6,733 (aged 64.9 ± 9.2 yrs) men and women from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Data were collected on self reported TV time and content, and physical activity. Nurses measured height and weight for the calculation of body mass index.
Results
On average, participants reported viewing TV for 5.3 ± 4.1 hours per day and 30.3% of the sample watched sport on TV at least twice a week. There was no association between watching sport and physical activity levels. Participants that watched sports every day were at higher risk of obesity [odds ratio = 1.39, 95% CI, 1.15, 1.68) after adjustment for age, sex, smoking, alcohol, physical activity, total TV time, disability, and self-rated health.
Conclusions
Watching elite athletes may have no role in the promotion of physical activity in older adults, which has implications for staging large sporting events with physical activity legacy promises.
doi:10.1186/1471-2458-14-10
PMCID: PMC3890601  PMID: 24400697
Ageing; Epidemiology; Health promotion; Obesity; Physical activity; Sedentary
17.  Socioeconomic status as a risk factor for dementia death: individual participant meta-analysis of 86 508 men and women from the UK* 
Background
Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base.
Aims
To examine the association between socioeconomic status in early life and adulthood with later dementia death.
Method
Individual participant meta-analysis of 11 prospective cohort studies (1994-2004, n = 86 508).
Results
Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ⩽14 v. age ⩾16: HR = 1.76, 95% CI 1.23-2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women.
Conclusions
Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities.
doi:10.1192/bjp.bp.112.119479
PMCID: PMC3696876  PMID: 23818534
18.  Influence of retirement on nonadherence to medication for hypertension and diabetes 
Background:
The extent to which common life transitions influence medication adherence among patients remains unknown. We examined whether retirement is associated with a change in adherence to medication in patients with hypertension or type 2 diabetes.
Methods:
Participants in the Finnish Public Sector study were linked to national registers. We included data for the years 1994–2011. We identified and followed 3468 adult patients with hypertension and 412 adult patients with type 2 diabetes for medication adherence for the 3 years before their retirement and the 4 years after their retirement (mean follow-up 6.8 yr). Our primary outcome was proportion of patients with poor adherence to medication, which we defined as less than 40% of days covered by treatment. We determined these proportions before and after retirement using data from filled prescriptions.
Results:
The preretirement prevalence of poor adherence to medication was 6% in men and women with hypertension, 2% in men with diabetes and 4% in women with diabetes. Among men, retirement was associated with an increased risk of poor adherence to both antihypertensive agents (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03–1.68) and antidiabetic drugs (OR 2.40, 95% CI 1.37–4.20). Among women, an increased risk of poor adherence was seen only for antihypertensive agents (OR 1.25, 95% CI 1.07–1.46). Similar results were apparent for alternative definitions of poor adherence. Our results did not differ across strata of age, socioeconomic status or comorbidity.
Interpretation:
We found a decline in adherence to medication after retirement among men and women with hypertension and men with type 2 diabetes. If these findings can be confirmed, we need randomized controlled trials to determine whether interventions to reduce poor adherence after retirement could improve clinical outcomes of treatments for hypertension and diabetes.
doi:10.1503/cmaj.122010
PMCID: PMC3832579  PMID: 24082018
19.  Active buildings: modelling physical activity and movement in office buildings. An observational study protocol 
BMJ Open  2013;3(11):e004103.
Introduction
Health benefits of regular participation in physical activity are well documented but population levels are low. Office layout, and in particular the number and location of office building destinations (eg, print and meeting rooms), may influence both walking time and characteristics of sitting time. No research to date has focused on the role that the layout of the indoor office environment plays in facilitating or inhibiting step counts and characteristics of sitting time. The primary aim of this study was to investigate associations between office layout and physical activity, as well as sitting time using objective measures.
Methods and analysis
Active buildings is a unique collaboration between public health, built environment and computer science researchers. The study involves objective monitoring complemented by a larger questionnaire arm. UK office buildings will be selected based on a variety of features, including office floor area and number of occupants. Questionnaires will include items on standard demographics, well-being, physical activity behaviour and putative socioecological correlates of workplace physical activity. Based on survey responses, approximately 30 participants will be recruited from each building into the objective monitoring arm. Participants will wear accelerometers (to monitor physical activity and sitting inside and outside the office) and a novel tracking device will be placed in the office (to record participant location) for five consecutive days. Data will be analysed using regression analyses, as well as novel agent-based modelling techniques.
Ethics and dissemination
The results of this study will be disseminated through peer-reviewed publications and scientific presentations. Ethical approval was obtained through the University College London Research Ethics Committee (Reference number 4400/001).
doi:10.1136/bmjopen-2013-004103
PMCID: PMC3831099  PMID: 24227873
Physical Activity; Sedentary Behaviour; Built Environment; Agent-based models; Office Buildings
20.  Chronic inflammation as a determinant of future aging phenotypes  
Background:
The importance of chronic inflammation as a determinant of aging phenotypes may have been underestimated in previous studies that used a single measurement of inflammatory markers. We assessed inflammatory markers twice over a 5-year exposure period to examine the association between chronic inflammation and future aging phenotypes in a large population of men and women.
Methods:
We obtained data for 3044 middle-aged adults (28.2% women) who were participating in the Whitehall II study and had no history of stroke, myocardial infarction or cancer at our study’s baseline (1997–1999). Interleukin-6 was measured at baseline and 5 years earlier. Cause-specific mortality, chronic disease and functioning were ascertained from hospital data, register linkage and clinical examinations. We used these data to create 4 aging phenotypes at the 10-year follow-up (2007–2009): successful aging (free of major chronic disease and with optimal physical, mental and cognitive functioning), incident fatal or nonfatal cardiovascular disease, death from noncardiovascular causes and normal aging (all other participants).
Results:
Of the 3044 participants, 721 (23.7%) met the criteria for successful aging at the 10-year follow-up, 321 (10.6%) had cardiovascular disease events, 147 (4.8%) died from noncardiovascular causes, and the remaining 1855 (60.9%) were included in the normal aging phenotype. After adjustment for potential confounders, having a high interleukin-6 level (> 2.0 ng/L) twice over the 5-year exposure period nearly halved the odds of successful aging at the 10-year follow-up (odds ratio [OR] 0.53, 95% confidence interval [CI] 0.38–0.74) and increased the risk of future cardiovascular events (OR 1.64, 95% CI 1.15–2.33) and noncardiovascular death (OR 2.43, 95% CI 1.58–3.80).
Interpretation:
Chronic inflammation, as ascertained by repeat measurements, was associated with a range of unhealthy aging phenotypes and a decreased likelihood of successful aging. Our results suggest that assessing long-term chronic inflammation by repeat measurement of interleukin-6 has the potential to guide clinical practice.
doi: 10.1503/cmaj.122072
PMCID: PMC3826354  PMID: 24043651
21.  Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts 
F1000Research  2013;2:233.
Background: Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted “job strain”) are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.
 
Methods: This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.
 
Discussion: The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.
doi:10.12688/f1000research.2-233.v1
PMCID: PMC3938244  PMID: 24627793
22.  Diabetes Risk Factors, Diabetes Risk Algorithms, and the Prediction of Future Frailty: The Whitehall II Prospective Cohort Study 
Objective
To examine whether established diabetes risk factors and diabetes risk algorithms are associated with future frailty.
Design
Prospective cohort study. Risk algorithms at baseline (1997–1999) were the Framingham Offspring, Cambridge, and Finnish diabetes risk scores.
Setting
Civil service departments in London, United Kingdom.
Participants
There were 2707 participants (72% men) aged 45 to 69 years at baseline assessment and free of diabetes.
Measurements
Risk factors (age, sex, family history of diabetes, body mass index, waist circumference, systolic and diastolic blood pressure, antihypertensive and corticosteroid treatments, history of high blood glucose, smoking status, physical activity, consumption of fruits and vegetables, fasting glucose, HDL-cholesterol, and triglycerides) were used to construct the risk algorithms. Frailty, assessed during a resurvey in 2007–2009, was denoted by the presence of 3 or more of the following indicators: self-reported exhaustion, low physical activity, slow walking speed, low grip strength, and weight loss; “prefrailty” was defined as having 2 or fewer of these indicators.
Results
After a mean follow-up of 10.5 years, 2.8% of the sample was classified as frail and 37.5% as prefrail. Increased age, being female, stopping smoking, low physical activity, and not having a daily consumption of fruits and vegetables were each associated with frailty or prefrailty. The Cambridge and Finnish diabetes risk scores were associated with frailty/prefrailty with odds ratios per 1 SD increase (disadvantage) in score of 1.18 (95% confidence interval: 1.09–1.27) and 1.27 (1.17–1.37), respectively.
Conclusion
Selected diabetes risk factors and risk scores are associated with subsequent frailty. Risk scores may have utility for frailty prediction in clinical practice.
doi:10.1016/j.jamda.2013.08.016
PMCID: PMC3820037  PMID: 24103860
Aging; frailty; diabetes risk scores; diabetes risk factors
23.  The Association Between Cortisol Response to Mental Stress and High-Sensitivity Cardiac Troponin T Plasma Concentration in Healthy Adults 
Objectives
The objective of this study was to examine the association between cortisol response to mental stress and high-sensitivity cardiac troponin T (hs-cTnT) in healthy older individuals without history of cardiovascular disease (CVD).
Background
Mental stress is a recognized risk factor for CVD, although the mechanisms remain unclear. Cortisol, a key stress hormone, is associated with coronary atherosclerosis and may accentuate structural and functional cardiac disease.
Methods
This cross-sectional study involved 508 disease-free men and women aged 53 to 76 years drawn from the Whitehall II epidemiological cohort. We evaluated salivary cortisol response to standardized mental stress tests (exposure) and hs-cTnT plasma concentration using a high-sensitivity assay (outcome). We measured coronary calcification using electron-beam dual-source computed tomography and Agatston scores.
Results
After adjustment for demographic and clinical variables associated with CVD as well as for inflammatory factors, we found a robust association between cortisol response and detectable hs-cTnT (odds ratio [OR]: 3.98; 95% confidence interval [CI]: 1.60 to 9.92; p = 0.003). The association remained when we restricted the analysis to participants without coronary calcification (n = 222; OR: 4.77; 95% CI: 1.22 to 18.72; p = 0.025) or when we further adjusted for coronary calcification in participants with positive Agatston scores (n = 286; OR: 7.39; 95% CI: 2.22 to 26.24; p = 0.001).
Conclusions
We found that heightened cortisol response to mental stress was associated with detectable plasma levels of cTnT using high-sensitivity assays in healthy participants, independently of coronary atherosclerosis. Further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage.
doi:10.1016/j.jacc.2013.05.070
PMCID: PMC3807660  PMID: 23810896
atherosclerotic plaque; computed tomography; myocardial infarction; psychological stress; troponin T; AMI, acute myocardial infarction; BMI, body mass index; CAC, coronary artery calcification; CRP, C-reactive protein; CVD, cardiovascular disease; hs-cTnT, high-sensitivity cardiac troponin T; IL, interleukin; HDL, high-density lipoprotein; LDL, low-density lipoprotein
24.  Objectively assessed sedentary time and type 2 diabetes mellitus: a case–control study 
Diabetologia  2013;56(12):2761-2762.
doi:10.1007/s00125-013-3051-5
PMCID: PMC3825498  PMID: 24078056
Accelerometry; Case–control; Physical activity; Sedentary; Type 2 diabetes mellitus
25.  Are Sitting Occupations Associated with Increased All-Cause, Cancer, and Cardiovascular Disease Mortality Risk? A Pooled Analysis of Seven British Population Cohorts 
PLoS ONE  2013;8(9):e73753.
Background
There is mounting evidence for associations between sedentary behaviours and adverse health outcomes, although the data on occupational sitting and mortality risk remain equivocal. The aim of this study was to determine the association between occupational sitting and cardiovascular, cancer and all-cause mortality in a pooled sample of seven British general population cohorts.
Methods
The sample comprised 5380 women and 5788 men in employment who were drawn from five Health Survey for England and two Scottish Health Survey cohorts. Participants were classified as reporting standing, walking or sitting in their work time and followed up over 12.9 years for mortality. Data were modelled using Cox proportional hazard regression adjusted for age, waist circumference, self-reported general health, frequency of alcohol intake, cigarette smoking, non-occupational physical activity, prevalent cardiovascular disease and cancer at baseline, psychological health, social class, and education.
Results
In total there were 754 all-cause deaths. In women, a standing/walking occupation was associated with lower risk of all-cause (fully adjusted hazard ratio [HR] = 0.68, 95% CI 0.52–0.89) and cancer (HR = 0.60, 95% CI 0.43–0.85) mortality, compared to sitting occupations. There were no associations in men. In analyses with combined occupational type and leisure-time physical activity, the risk of all-cause mortality was lowest in participants with non-sitting occupations and high leisure-time activity.
Conclusions
Sitting occupations are linked to increased risk for all-cause and cancer mortality in women only, but no such associations exist for cardiovascular mortality in men or women.
doi:10.1371/journal.pone.0073753
PMCID: PMC3784430  PMID: 24086292

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