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To characterize geospatial patterning of disadvantage in Sweden, we examined whether municipal-level indicators of socioeconomic disadvantage and disability pension (DP) rate were clustered, whether the different geospatial clusters were overlapping and whether the findings were similar among women and men.Administrative national data from all 290 Swedish municipalities were used to determine the prevalence of DP and socioeconomic disadvantage [poverty, long-term unemployment, income inequality (GINI Index) and income inequality between women and men]. Geospatial cold spots (clusters of municipalities with a DP/socioeconomic disadvantage prevalence lower than the nationwide prevalence) and hot spots (clusters of municipalities with a DP/socioeconomic disadvantage higher than the nationwide prevalence) were identified, and whether a hot spot was overlapping with another hot spot and a cold spot overlapping with another cold spot were analysed using the Getis-Ord Gi statistics.Among women and men, cold spots of DP were most consistently located in the Stockholm area. Hot spots of DP were found in the mid-south Sweden, characterized by mid-sized urban centres in rural territories. High DP rate and socioeconomic disadvantage were overlapping, except for income inequality. Clusters of gender income inequality and women's high DP rate were observed in mid-south Sweden.DP and socioeconomic disadvantage are not randomly distributed in Sweden. Geospatial analyses revealed clusters of municipalities with high risk of both DP and socioeconomic disadvantage in certain areas and low risk in other areas. Further research is needed to identify preventive actions to decrease regional inequalities in work capacity.

The aim of this study was to examine patterns of 10-year survival after elective repair of unruptured abdominal aortic aneurysms (AAAs) in different patient groups.Patients having open repair or endovascular aneurysm repair (EVAR) in the English National Health Service between January 2006 and December 2015 were identified from Hospital Episode Statistics data. Postoperative survival among patients of different age and Royal College of Surgeons of England (RCS) modified Charlson co-morbidity score profiles were analysed using flexible parametric survival models. The relationship between patient characteristics and risk of rupture after repair was also analysed.Some 37 138 patients underwent elective AAA repair, of which 15 523 were open and 21 615 were endovascular. The 10-year mortality rate was 38·1 per cent for patients aged under 70 years, and the survival trajectories for open repair and EVAR were similar when patients had no RCS-modified Charlson co-morbidity. Among older patients or those with co-morbidity, the 10-year mortality rate rose, exceeding 70 per cent for patients aged 80 years. Mean survival times over 10 years for open repair and EVAR were often similar in subgroups of older and more co-morbid patients, but their survival trajectories became increasingly dissimilar, with open repair showing greater short-term risk within 6 months but lower 10-year mortality rates. The risk of rupture over 9 years was 3·4 per cent for EVAR and 0·9 per cent for open repair, and was weakly associated with patient factors.Long-term survival patterns after elective open repair and EVAR for unruptured AAA vary markedly across patients with different age and co-morbidity profiles.El objetivo de este artículo fue examinar los patrones de supervivencia a 10 aáos tras reparación electiva de aneurismas de la aorta abdominal sin rotura (abdominal aortic aneurysms, AAA) en diferentes grupos de pacientes. MÉTODOS: Se identificaron pacientes sometidos a reparación abierta (open repair, OR) o reparación endovascular (endovascular aneurysm repair, EVAR) del aneurisma en el Sistema Nacional de Salud Inglés entre enero de 2006 y diciembre de 2015, a partir de los datos del Hospital Episode Statistics. Se analizaron la supervivencia postoperatoria entre los pacientes de diferentes edades y los perfiles de comorbilidad con la puntuación de Charlson modificada del Royal College of Surgeons of England (RCS) utilizando modelos de supervivencia paramétricos flexibles. También se analizó la relación entre las características de los pacientes y el riesgo de rotura tras la reparación.Un total de 37.138 pacientes fueron sometidos a reparaciones electivas de AAA, de las cuales 15.523 fueron reparaciones abiertas y 21.615 endovasculares. La mortalidad a los 10 aáos fue del 38% para los pacientes de edad inferior a los 70 aáos, y las curvas de supervivencia de la OR y EVAR fueron similares cuando los pacientes no tenían comorbilidad con el Charlson modificado del RCS. Entre los pacientes de edad avanzada y aquellos pacientes con comorbilidad, la mortalidad a los 10 aáos aumentó, excediendo el 70% para los pacientes de más de 80 aáos de edad. La media de los tiempos de supervivencia superior a 10 aáos para OR y EVAR fueron similares dentro de los subgrupos de pacientes de edad avanzada y más comorbilidad, pero las curvas de supervivencia se hicieron cada vez más diferentes, con la OR mostrando un mayor riesgo a corto plazo en los primeros 6 meses pero tasas de mortalidad a los 10 aáos más bajas. El riesgo de rotura mas allá de los 9 aáos fue 3,4% para EVAR y 0,9% para la reparación abierta, con una débil asociación con los factores inherentes a los pacientes. CONCLUSIÓN: Los patrones de supervivencia a largo plazo tras OR y EVAR electivas para AAA sin rotura varían notablemente entre pacientes con perfiles de edad y comorbilidad diferentes.

Background Whether clustering of social disadvantage in young adulthood is associated with attention-deficit/hyperactivity disorder (ADHD) is poorly understood. We examined clustering of ADHD with low educational attainment and unemployment in young adulthood; whether such clustering is stronger when unemployment was prolonged; and whether further clustering of disability pensioning, low education and unemployment occurs among those with ADHD. Methods Data were obtained from Swedish health, demographic and social security registers from which 8990 individuals with recorded ADHD diagnoses at the age of 10 to 35 and their 44387 matched references without mental disorders. Social disadvantage was measured using data on educational attainment, unemployment and disability pension from the diagnosis year or age 19 if diagnosed at younger age. Clustering was examined by comparing observed and expected occurrence (O/E ratio) of all possible combinations of ADHD, low education and unemployment, and, among those with ADHD, additional combinations with new-onset disability pension. Results The likelihood of having neither ADHD, low education nor unemployment was increased (O/E ratio = 1.20, 95% confidence interval 1.19–1.20 at baseline; 1.18, 1.17–1.18 at follow-up), as well as having all three characteristics (O/E ratio = 3.99, 3.89–4.10 at baseline; 5.68, 5.47–5.89 at follow-up). This clustering was stronger among women than men and when unemployment was prolonged. Among individuals with ADHD, clustering of low education with disability pension and unemployment was observed. Conclusions Low education and unemployment appear to cluster remarkably with ADHD among young adults, more so among women and when unemployment is prolonged.

Background People who were born prematurely have high risks of many individual diseases and conditions in the early part of the life course. However, our knowledge of the burden of multiple diseases (multimorbidity) among prematurely born individuals is limited. We aimed to investigate the risk and patterns of chronic disease multimorbidity in adolescence and early adulthood among individuals born across the spectrum of gestational ages, comparing preterm and full-term born individuals. Methods and findings We used individual-level data from linked nationwide registers to examine the associations of gestational age at birth with specialised healthcare records of ≥2 chronic diseases (multimorbidity) in adolescence (age 10–17 years) and early adulthood (age 18–30 years). Our study population comprised 951,116 individuals (50.2% females) born alive in Finland between 1st January 1987 and 31st December 2006, inclusive. All individuals were followed from age 10 years to the onset of multimorbidity, emigration, death, or 31 December 2016 (up to age 30 years). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for multimorbidity using flexible parametric survival models. During 6,417,903 person-years at risk (median follow-up: 7.9 years), 11,919 individuals (1.3%) had multimorbidity in adolescence (18.6 per 10,000 person-years). During 3,967,419 person-years at risk (median follow-up: 6.2 years), 15,664 individuals (1.7%) had multimorbidity in early adulthood (39.5 per 10,000 person-years). Adjusted HRs for adolescent multimorbidity, comparing preterm to full-term born individuals, were 1.29 (95% CI: 1.22 to 1.36) and 1.26 (95% CI: 1.18 to 1.35) in females and males, respectively. The associations of preterm birth with early adult multimorbidity were less marked, with the adjusted HRs indicating 1.18-fold risk in females (95% CI: 1.12 to 1.24) and 1.10-fold risk in males (95% CI: 1.04 to 1.17). We observed a consistent dose-response relationship between earlier gestational age at birth and increasing risks of both multimorbidity outcomes. Compared to full-term born males, those born at 37–38 weeks (early term) had a 1.06-fold risk of multimorbidity in adolescence (95% CI: 0.98 to 1.14) and this risk increased in a graded manner up to 6.85-fold (95% CI: 5.39 to 8.71) in those born at 23–27 weeks (extremely premature), independently of covariates. Among females, the same risks ranged from 1.16-fold (95% CI: 1.09 to 1.23) among those born at 37–38 weeks to 5.65-fold (95% CI: 4.45 to 7.18) among those born at 23–27 weeks. The corresponding risks of early adult multimorbidity were similar in direction but less marked in magnitude, with little difference in risks between males and females born at 36–37 weeks but up to 3-fold risks observed among those born at 23–27 weeks. Conclusions Our findings indicate that an earlier gestational age at birth is associated with increased risks of chronic disease multimorbidity in the early part of the life course. There are currently no clinical guidelines for follow-up of prematurely born individuals beyond childhood, but these observations suggest that information on gestational age would be a useful characteristic to include in a medical history when assessing the risk of multiple chronic diseases in adolescent and young adult patients.

This cohort study examines disease-free life-years in participants with varying combinations of lifestyle risk factors. Question Are different combinations of lifestyle factors associated with years lived without chronic diseases? Findings In a multicohort study of 116 & x202f;043 participants, a statistically significant association between overall healthy lifestyle score and an increased number of disease-free life-years was noted. Of 16 different lifestyle profiles studied, the 4 that were associated with the greatest disease-free life years included body mass index lower than 25 and at least 2 of 3 factors: never smoking, physical activity, and moderate alcohol consumption. Meaning Various healthy lifestyle profiles appear to be associated with extended gains in life lived without type 2 diabetes, cardiovascular and respiratory diseases, and cancer. Importance It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown. Objective To estimate the association between healthy lifestyle and the number of disease-free life-years. Design, Setting, and Participants A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 & x202f;043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020. Exposures Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors. Main Outcomes and Measures The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease. Results Of the 116 & x202f;043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 & x202f;911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 & x202f;383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P

Background Job strain is implicated in many atherosclerotic diseases, but its role in peripheral artery disease ( PAD ) is unclear. We investigated the association of job strain with hospital records of PAD , using individual‐level data from 11 prospective cohort studies from Finland, Sweden, Denmark, and the United Kingdom. Methods and Results Job strain (high demands and low control at work) was self‐reported at baseline (1985–2008). PAD records were ascertained from national hospitalization data. We used Cox regression to examine the associations of job strain with PAD in each study, and combined the study‐specific estimates in random effects meta‐analyses. We used τ 2 , I 2 , and subgroup analyses to examine heterogeneity. Of the 139 132 participants with no previous hospitalization with PAD , 32 489 (23.4%) reported job strain at baseline. During 1 718 132 person‐years at risk (mean follow‐up 12.8 years), 667 individuals had a hospital record of PAD (3.88 per 10 000 person‐years). Job strain was associated with a 1.41‐fold (95% CI, 1.11–1.80) increased average risk of hospitalization with PAD . The study‐specific estimates were moderately heterogeneous (τ 2 =0.0427, I 2 : 26.9%). Despite variation in their magnitude, the estimates were consistent in both sexes, across the socioeconomic hierarchy and by baseline smoking status. Additional adjustment for baseline diabetes mellitus did not change the direction or magnitude of the observed associations. Conclusions Job strain was associated with small but consistent increase in the risk of hospitalization with PAD , with the relative risks on par with those for coronary heart disease and ischemic stroke.

Background: The availability and diversity of lower limb revascularization procedures have increased in England in the past decade. We investigated whether these developments in care have translated to improvements in patient pathways and outcomes. Methods: Individual-patient records from Hospital Episode Statistics were used to identify 103 934 patients who underwent endovascular (angioplasty) or surgical (endarterectomy, profundaplasty, or bypass) lower limb revascularization for infrainguinal peripheral artery disease in England between January 2006 and December 2015. Major lower limb amputations and deaths within 1 year after revascularization were ascertained from Hospital Episode Statistics and Office for National Statistics mortality records. Competing risks regression was used to estimate the cumulative incidence of major amputation and death, adjusted for patient age, sex, comorbidity score, indication for the intervention (intermittent claudication, severe limb ischemia without record of tissue loss, severe limb ischemia with a record of ulceration, severe limb ischemia with a record of gangrene/osteomyelitis), and comorbid diabetes mellitus. Results: The estimated 1-year risk of major amputation decreased from 5.7% (in 2006–2007) to 3.9% (in 2014–2015) following endovascular revascularization, and from 11.2% (2006–2007) to 6.6% (2014–2015) following surgical procedures. The risk of death after both types of revascularization also decreased. These trends were observed for all indication categories, with the largest reductions found in patients with severe limb ischemia with ulceration or gangrene. Overall, morbidity increased over the study period, and a larger proportion of patients was treated for the severe end of the peripheral artery disease spectrum using less invasive procedures. Conclusions: Our findings show that from 2006 to 2015, the overall survival increased and the risk of major lower limb amputation decreased following revascularization. These observations suggest that patient outcomes after lower limb revascularization have improved during a period of centralization and specialization of vascular services in the United Kingdom.

Background The aim of this study was to estimate separate risks of major lower limb amputation and death following revascularization for peripheral artery disease (PAD) using competing risks analysis. Methods Routinely collected data from Hospital Episode Statistics (HES) were used to identify patients who underwent endovascular or open lower limb revascularization for PAD in England from 2005 to 2015. The primary outcomes were major lower limb amputation and death within 5 years of revascularization. Cox proportional hazards and Fine–Gray competing risks regression were used to examine the competing risks of these outcomes. Results Some 164 845 patients underwent their first lower limb revascularization for PAD during the study interval. Most were men (64·6 per cent) and the median age was 71 (i.q.r. 62–78) years. Following endovascular revascularization, the 5-year cumulative incidence of amputation was 4·2 per cent in patients with intermittent claudication and 18·0 per cent in those with a record of tissue loss. The corresponding rates were 10·8 and 25·3 per cent respectively after open revascularization, and 8·1 and 25·0 per cent after combined procedures. The 5-year cumulative incidence of death varied from 24·5 to 39·8 per cent, depending on procedure type. Competing risks methods consistently produced lower estimates than standard methods. Conclusion The 5-year risk of major amputation following lower limb revascularization for PAD appears lower than estimated previously. Patients undergoing revascularization for tissue loss and those who require an open procedure are at highest risk of limb loss.

Background and aims Clinical experience and observational studies suggest that individuals with coeliac disease are at increased risk of coronary heart disease (CHD), but the precise mechanism for this is unclear. Laboratory studies suggest that it may relate to tissue transglutaminase antibodies (tTGAs). Our aim was to examine whether seropositivity for tTGA and endomysial antibodies (EMAs) are associated with incident CHD in humans. Methods and results We used data from Mini-Finland Health Survey, a prospective cohort study of Finnish men and women aged 35–80 at study baseline 1978–80. TTGA and EMA seropositivities were ascertained from baseline blood samples and incident CHD events were identified from national hospitalisation and death registers. Cox regression was used to examine the associations between antibody seropositivity and incident CHD. Of 6887 men and women, 562 were seropositive for tTGAs and 72 for EMAs. During a median follow-up of 26 years, 2367 individuals experienced a CHD event. We found no clear evidence for an association between tTGA positivity (hazard ratio, HR: 1.04, 95% confidence interval, CI: 0.83, 1.30) or EMA positivity (HR: 1.16, 95% CI: 0.77, 1.74) and incident CHD, once pre-existing CVD and known CHD risk factors had been adjusted for. Conclusion We found no clear evidence for an association of tTGA or EMA seropositivity with incident CHD outcomes, suggesting that tTG autoimmunity is unlikely to be the biological link between coeliac disease and CHD.

Objectives This systematic review and meta-analysis combined published study-level data and unpublished individual-participant data with the aim of quantifying the relation between long working hours and the onset of depressive symptoms. Methods We searched PubMed and Embase for published prospective cohort studies and included available cohorts with unpublished individual-participant data. We used a random-effects meta-analysis to calculate summary estimates across studies. Results We identified ten published cohort studies and included unpublished individual-participant data from 18 studies. In the majority of cohorts, long working hours was defined as working ≥55 hours per week. In multivariable-adjusted meta-analyses of 189 729 participants from 35 countries [96 275 men, 93 454 women, follow-up ranging from 1-5 years, 21 747 new-onset cases), there was an overall association of 1.14 (95% confidence interval (CI) 1.03-1.25] between long working hours and the onset of depressive symptoms, with significant evidence of heterogeneity (I 2=45.1%, P=0.004). A moderate association between working hours and depressive symptoms was found in Asian countries (1.50, 95% CI 1.13-2.01), a weaker association in Europe (1.11, 95% CI 1.00-1.22), and no association in North America (0.97, 95% CI 0.70-1.34) or Australia (0.95, 95% CI 0.70-1.29). Differences by other characteristics were small. Conclusions This observational evidence suggests a moderate association between long working hours and onset of depressive symptoms in Asia and a small association in Europe. CC BY 4.0

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 ( I 2 =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, I 2 =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, I 2 =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.

Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health. CODEN: LANCA

Background Evidence from prospective observational studies suggests that elevated circulating C-reactive protein (CRP) concentrations are associated with cancer risk, but it is unclear whether this association is causal. In order to examine this, we investigated whether genetic variants that are associated with circulating CRP concentrations are associated with cancer risk. Methods We pooled data from three population-based prospective Finnish studies: FINRISK 1992 ( n = 5289), FINRISK 1997 ( n = 7160) and Health 2000 ( n = 6299). Cancer cases were identified from cancer registrations. Thirteen CRP-associated SNPs, identified from genome-wide association studies, were genotyped. We examined the associations of the SNPs and cancer risk using Cox, probit and instrumented probit regression models. Results Compared to common allele homozygotes, individuals carrying one or two variant T alleles at rs1892534 had 1.05-fold (95% confidence interval (CI): 0.90, 1.23) and 1.2-fold (95% CI: 1.01, 1.42) increased overall cancer risk, respectively. Individuals with one or two variant A alleles at rs1169300 or rs2464196 had approximately 1.5- and 2-fold increased risk of lung cancer, respectively (p trend for both: 0.007). CRP SNPs were not associated with colorectal, prostate or breast cancer risk nor was CRP-associated with the probability of developing cancer in the instrumented probit analyses. Conclusions We found some evidence for an association of a small number of CRP-associated SNPs with the overall cancer risk and lung cancer risk. Our instrumental variable analyses provided no clear evidence for a causal association of CRP and cancer. These findings suggest that circulating CRP concentrations are unlikely to have a causal role in cancer.

We investigated the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) with cancer risk. We examined the associations of CRP and IL-6 with incident cancer in two prospective cohorts, the British Women’s Heart and Health Study (4,286 women aged 60–80) and the Caerphilly Cohort (2,398 men aged 45–59) using Cox regression and pooled our findings with previous prospective studies’ in fixed and random effects meta-analyses. CRP and IL-6 were associated with some incident cancers in our cohorts, but the numbers of cancer cases were small. In our meta-analyses elevated CRP was associated with an increased overall risk of cancer (random effects estimate (RE): 1.10, 95% CI: 1.02, 1.18) and lung cancer (RE: 1.32, 95% CI: 1.08, 1.61). Its associations with colorectal (RE: 1.09, 95% CI: 0.98, 1.21) and breast cancer risks (RE: 1.10, 95% CI: 0.97, 1.26) were weaker. CRP appeared unrelated to prostate cancer risk (RE: 1.00 0.88, 1.13). IL-6 was associated with increased lung and breast cancer risks and decreased prostate cancer risk, and was unrelated to colorectal cancer risk. Our findings suggest an etiological role for CRP and IL-6 in some cancers. Further large prospective and genetic studies would help to better understand this role.

The objective of this study was to review and summarise the published evidence for an association between circulating concentrations of C reactive protein (CRP) and cancer through a systematic review. 90 discrete studies were identified. 81 (90%) were prevalent case–control or cross‐sectional studies, and only 9 studies had a prospective design. In most prevalent studies, CRP concentrations were found to be higher in patients with cancer than in healthy controls or controls with benign conditions. Of the nine large prospective studies identified in this review, four reported no relationship between circulating CRP levels and breast, prostate or colorectal cancers, and five studies found that CRP was associated with colorectal or lung cancers. Most of the studies evaluating CRP as a diagnostic marker of cancer did not present relevant statistical analyses. Furthermore, any association reported in the prevalent studies might reflect reverse causation, survival bias or confounding. The prospective studies provided no strong evidence for a causal role of CRP in cancer. Instead of further prevalent studies, more large prospective studies and CRP gene–cancer association studies would be valuable in investigating the role of CRP in cancer.

Background: Inflammation is associated with worse prognosis and survival in many cancers. Our aim was to investigate the associations of circulating C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations with all-cause mortality in cancer patients and to determine whether any associations were specific to malignancy. Method: We used data from the British Women's Heart and Health Study, a cohort of 4,286 women aged 60 to 79 years. We investigated the associations between CRP, IL-6, and survival in women with and without cancer using Cox regression and assessed the interaction between cancer status and these inflammatory markers to determine whether these associations differed according to cancer status. Results: Elevated CRP and IL-6 were associated with decreased survival in women with cancer [unadjusted hazard ratio per doubling of CRP, 1.22, 95% confidence interval (95% CI), 1.03, 1.46; and per doubling of IL-6, 1.52, 95% CI, 1.25, 1.86] and in women without cancer [CRP: 1.24 (1.12, 1.37); IL-6: 1.53 (1.35, 1.75)]. Adjustment for age, body mass index, physical activity level, socioeconomic position, HRT use, and tobacco smoking did not change these associations. After mutual adjustment, IL-6 but not CRP was independently associated with survival. We found no strong evidence that these associations differed between cancer patients and cancer-free women. Conclusions: Elevated CRP and IL-6 concentrations were similarly associated with an increased risk of death in elderly women with and without cancer. Thus, in this group, these markers are likely to be indicators of non-cancer comorbidities rather than related to the malignancy itself. (Cancer Epidemiol Biomarkers Prev 2007;16(6):1155–9)

Background and Purpose— Psychosocial stress at work has been proposed to be a risk factor for cardiovascular disease. However, its role as a risk factor for stroke is uncertain. Methods— We conducted an individual-participant-data meta-analysis of 196 380 males and females from 14 European cohort studies to investigate the association between job strain, a measure of work-related stress, and incident stroke. Results— In 1.8 million person-years at risk (mean follow-up 9.2 years), 2023 first-time stroke events were recorded. The age- and sex-adjusted hazard ratio for job strain relative to no job strain was 1.24 (95% confidence interval, 1.05;1.47) for ischemic stroke, 1.01 (95% confidence interval, 0.75;1.36) for hemorrhagic stroke, and 1.09 (95% confidence interval, 0.94;1.26) for overall stroke. The association with ischemic stroke was robust to further adjustment for socioeconomic status. Conclusion— Job strain may be associated with an increased risk of ischemic stroke, but further research is needed to determine whether interventions targeting job strain would reduce stroke risk beyond existing preventive strategies.

The impact of celiac disease autoimmunity on bone health is unclear. We investigated the associations of seropositivity for tissue transglutaminase antibodies (tTGA) and endomysial antibodies (EMA) with incident hip fractures using data from a prospective cohort study, Mini-Finland Health Survey. Baseline serum samples, taken in 1978-80, were tested for tTGA and EMA. Incident hip fractures up to the year 2011 were ascertained from a national hospitalization register. Associations between seropositivity and hip fractures were modeled using Cox proportional hazards regression adjusted for age, sex, body mass index, vitamin D, gamma-glutamyl transferase, smoking, and self-rated health. Our analyses were based on 6919 men and women who had no record of celiac disease or hip fracture before the study baseline. A total of 382 individuals had a hip fracture during a median follow-up of 30 years. Compared with the tTGA-negative individuals (n = 6350), tTGA-positive participants (n = 569; with hip fracture, n = 51) had a higher risk of hip fractures (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.17, 2.14). The findings were similar for another tTGA test (n 200; with hip fracture, n = 26; HR = 2.23, 95% CI 1.49, 3.34). We found no evidence for an association between EMA positivity and hip fracture risk (HR = 0.92, 95% CI 0.34, 2.47; n = 74; with hip fracture, n = 4). In our prospective population-based study of Finnish adults, seropositivity for tTGA was associated with an increased hip fracture risk.

Background: Effort-reward imbalance (ERI) is an established conceptualisation of work stress. Although a validated effort-reward questionnaire is available for public use, many epidemiological studies adopt shortened scales and proxy measures. To examine the agreement between different abbreviated measures and the original instrument, we compared different versions of the effort-reward scales available in 15 European cohort studies participating in the IPD-Work (Individual-participant-data meta-analysis in working populations) consortium. Methods: Five of the 15 studies provide information on the original (‘complete’) scales measuring ‘effort’ and ‘reward’, whereas the 10 remaining studies used ‘partial’ scales. To compare different versions of the ERI scales, we analyse individual-level data from 31,790 participants from the five studies with complete scales. Results: Pearson’s correlation between partial and complete scales was very high in case of ‘effort’ (where 2 out of 3 items were used) and very high or high in case of ‘reward’, if at least 4 items (out of 7) were included. Reward scales composed of 3 items revealed good to satisfactory agreement, and in one case, a reward scale consisting of 2 items only demonstrated a modest, but still acceptable degree of agreement. Sensitivity and specificity of a composite measure, the ratio of effort and reward, comparing partial versus complete scales ranged between 59–93 and 85–99 %, respectively. Complete and partial scales were strongly associated with poor self-rated health. Conclusion: Our results support the notion that short proxy measures or partial versions of the original scales can be used to assess effort-reward imbalance. The final publication is available at www.springerlink.com: http://dx.doi.org/10.1007/s00420-013-0855-z

OBJECTIVE The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as “job strain,” is associated with incident type 2 diabetes independent of lifestyle factors. RESEARCH DESIGN AND METHODS We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses. RESULTS There were 3,703 cases of incident diabetes during a mean follow-up of 10.3 years. After adjustment for age, sex, and socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no job strain was 1.15 (95% CI 1.06–1.25) with no difference between men and women (1.19 [1.06–1.34] and 1.13 [1.00–1.28], respectively). In stratified analyses, job strain was associated with an increased risk of diabetes among those with healthy and unhealthy lifestyle habits. In a multivariable model adjusted for age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00–1.23). CONCLUSIONS Findings from a large pan-European dataset suggest that job strain is a risk factor for type 2 diabetes in men and women independent of lifestyle factors.

Background: It is unclear whether a healthy lifestyle mitigates the adverse effects of job strain on coronary artery disease. We examined the associations of job strain and lifestyle risk factors with the risk of coronary artery disease. Methods: We pooled individual-level data from 7 cohort studies comprising 102 128 men and women who were free of existing coronary artery disease at baseline (1985-2000). Questionnaires were used to measure job strain (yes v. no) and 4 lifestyle risk factors: current smoking, physical inactivity, heavy drinking and obesity. We grouped participants into 3 lifestyle categories: healthy (no lifestyle risk factors), moderately unhealthy (1 risk factor) and unhealthy (2-4 risk factors). The primary outcome was incident coronary artery disease (defined as first nonfatal myocardial infarction or cardiac-related death). Results: There were 1086 incident events in 743 948 person-years at risk during a mean follow-up of 7.3 years. The risk of coronary artery disease among people who had an unhealthy lifestyle compared with those who had a healthy lifestyle (hazard ratio [HR] 2.55, 95% confidence interval [CI] 2.18-2.98; population attributable risk 26.4%) was higher than the risk among participants who had job strain compared with those who had no job strain (HR 1.25, 95% CI 1.06-1.47; population attributable risk 3.8%). The 10-year incidence of coronary artery disease among participants with job strain and a healthy lifestyle (14.7 per 1000) was 53% lower than the incidence among those with job strain and an unhealthy lifestyle (31.2 per 1000). Interpretation: The risk of coronary artery disease was highest among participants who reported job strain and an unhealthy lifestyle; those with job strain and a healthy lifestyle had half the rate of disease. A healthy life style may substantially reduce disease risk among people with job strain.

Objective To investigate whether work related stress, measured and defined as job strain, is associated with the overall risk of cancer and the risk of colorectal, lung, breast, or prostate cancers.Design Meta-analysis of pooled prospective individual participant data from 12 European cohort studies including 116 056 men and women aged 17-70 who were free from cancer at study baseline and were followed-up for a median of 12 years. Work stress was measured and defined as job strain, which was self reported at baseline. Incident cancers (all n=5765, colorectal cancer n=522, lung cancer n=374, breast cancer n=1010, prostate cancer n=865) were ascertained from cancer, hospital admission, and death registers. Data were analysed in each study with Cox regression and the study specific estimates pooled in meta-analyses. Models were adjusted for age, sex, socioeconomic position, body mass index (BMI), smoking, and alcohol intakeResults A harmonised measure of work stress, high job strain, was not associated with overall risk of cancer (hazard ratio 0.97, 95% confidence interval 0.90 to 1.04) in the multivariable adjusted analyses. Similarly, no association was observed between job strain and the risk of colorectal (1.16, 0.90 to 1.48), lung (1.17, 0.88 to 1.54), breast (0.97, 0.82 to 1.14), or prostate (0.86, 0.68 to 1.09) cancers. There was no clear evidence for an association between the categories of job strain and the risk of cancer.Conclusions These findings suggest that work related stress, measured and defined as job strain, at baseline is unlikely to be an important risk factor for colorectal, lung, breast, or prostate cancers.

Job strain is associated with an increased coronary heart disease risk, but few large-scale studies have examined the relationship of this psychosocial characteristic with the biological risk factors that potentially mediate the job strain - heart disease association., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Objectives. We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. Methods. We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118 701; longitudinal data: n = 43 971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. Results. Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). Conclusions. Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between work-related stress and lifestyle. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e8. doi:10.2105/AJPH.2012.301090). AuthorCount: 32:Other Funders:Finnish Work Environment Fund; German Social Accident Insurance; Academy of Finland 132944; BUPA Foundation 22094477; Heinz Nixdorf Foundation (Germany;) German Ministry of Education and Science ; German Research Foundation; Medical Research Council (United Kingdom); Economic and Social Research Council professorial fellowship . IPD-Work Consortium

The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake., Journal Article, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

Objective To examine whether breast feeding is associated with behavioural development in children aged 5 years. Design The authors used data from a large, prospective, nationally representative UK cohort, the Millennium Cohort Study. Participants 10 037 mother–child pairs from white ethnic background (9525 term and 512 preterm children) were included in the analyses. Methods Duration of breast feeding (at all or exclusively) was ascertained from parental interview at study baseline, when the children were aged 9 months. Child behaviour was assessed using a parent-completed questionnaire, the Strengths and Difficulties Questionnaire (SDQ). The authors used logistic regression to investigate the associations of breastfeeding duration with abnormal parent-rated SDQ total and subscores at age 5 in term and preterm children separately. Results Abnormal SDQ scores were less common in term children (n=1129/9525, 12%) than pre-term (n=78/512, 15%) children. Term children breast fed for 4 months or longer (n=2741/9525, 29%) had lower odds of an abnormal total SDQ score (multivariable-adjusted OR compared with never breastfed children (n=3292/9525, 35%) 0.67, 95% CI: 0.54 to 0.83). This effect was similar for all the SDQ subscores. In preterm children, longer duration of breast feeding was generally associated with lower odds of abnormal SDQ total and subscores but the effect estimates were imprecise. The associations between exclusive breast feeding and abnormal SDQ scores were similar to those of any breast feeding and abnormal SDQ scores. Conclusions The findings suggest that, at least in term children, longer duration of breast feeding is associated with fewer parent-rated behavioural problems in children aged 5 years.

OBJECTIVE: To describe the worries experienced by pregnant Black and Minority Ethnic (BME) women about labour and birth and compare their experience to that of White women. DESIGN: Data were collected in England in a survey of experience of maternity care. A random sample of 4800 women selected from birth registration records and questionnaires were mailed at three months postpartum. A total of 2960 (63%) completed a checklist of common worries about labour and birth. For 2765 there were complete data on ethnicity and all potential confounders. Chi(2) tests and logistic regression models were used to investigate the associations of ethnicity with worries about labour. Unadjusted and adjusted models were run for each worry outcome. Adjustment was made for age, education, parity, relationship status and area deprivation (Index of Multiple Deprivation, IMD). RESULTS: Overall, the pattern of worries was similar, however, larger proportions of BME women worried about almost all the aspects of labour and birth investigated, including pain, uncertainty about labour onset and duration, possible medical interventions and embarrassment. After adjustment for age, education, relationship status, parity and socioeconomic position, the higher odds of worry in the BME group were most marked in relation to pain and discomfort, not knowing how long labour would take, embarrassment and having more worries overall. Further adjustment for factors likely to affect women's worries, namely depression, being admitted to hospital during the pregnancy, or having experienced medical problems in a previous pregnancy did not alter these findings. CONCLUSION: Compared with White women, twice as many ethnic minority women worried about pain and discomfort, not knowing how long labour would take and about embarrassment during labour and birth. Additional research is needed to understand these concerns and how they might be ameliorated by the health professionals working directly with women and any services changes needed to improve the quality of maternity care. Implications for practice include improved information-giving and support in providing the individualised care that women need.