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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.

Preterm birth affects lungs in several ways but only few studies have follow-up until adulthood. We investigated the association of the entire spectrum of gestational ages with specialist care episodes for obstructive airway disease (asthma and chronic obstructive pulmonary disease, COPD) at age 18–50 years. We used nationwide register data on 706 717 people born 1987–1998 in Finland (4.8% preterm) and 1 669 528 born 1967–1999 in Norway (5.0% preterm). Care episodes of asthma and COPD were obtained from specialised healthcare registers, available in Finland 2005–2016 and in Norway 2008–2017. We used logistic regression to estimate odds ratios (OR) for having a care episode with either disease outcome. Odds of any obstructive airway disease in adulthood were 2–3-fold for those born

Objectives To investigate working life courses in women and men and possible associations with socioeconomic, health-, and work-related factors. Methods A 15-year prospective cohort study of individuals aged 18–50 in paid work at baseline and answering the Swedish Living Conditions Surveys (2000–2003, N = 9269) and their annual economic activity, using nationwide registers. We used sequence and cluster analyses to identify and group similar working life sequences. Multinomial logistic regression was used to examine associations of sex, socioeconomic, health-, and work-related factors with sequence cluster memberships. Results We identified 1284 working life sequences, of which 65% represented continuous active (in paid work/studying) states. We then identified five sequence clusters, the largest one with individuals who were continuously active (n = 6034, 65% of the participants; 54% of women and 76% of men) and smaller ones with interruptions of the active state by long-term parental-leave, unemployment, and/or sickness absence/disability pension (SA/DP), or retirement. Women were more likely than men to belong to the “Parental-leave periods” (odds ratio [OR]: 33.2; 95% confidence intervals [CI]: 25.6, 43.1) and the “SA/DP periods” sequence clusters (OR: 1.8; 95% CI: 1.4, 2.1), also after adjustment for covariates. In both sexes, low education and poor health were the strongest predictors of belonging to the sequence cluster “Unemployment & SA/DP periods”. Predictors of the “Parental-leave periods” sequence cluster differed between women and men. Conclusions In a cohort of individuals in paid work at baseline, the majority of women and men worked most of each year although women were more likely to have some interruptions characterized by long-term parental-leave or SA/DP periods than men, independently of socioeconomic, health-, and work-related factors.

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 and Purpose— Carotid endarterectomy (CEA) reduces the risk of stroke in recently symptomatic patients and less so in asymptomatic patients. Recent evidence suggests that the number of CEAs may be declining. The aim of this study was to investigate annual patterns of CEA in asymptomatic and symptomatic patients in England from 2011 to 2017. Methods— Data from the National Vascular Registry were used to describe (1) the number of CEA procedures in England and its 9 geographic regions from 2011 to 2017, (2) the characteristics of patients undergoing CEA, and (3) whether rates of CEA correlated with the number of vascular arterial units within each region. Annual stroke incidence for each region was derived from official population figures and the number of index stroke admissions per year. Results— The overall number of CEAs performed in England fell from 4992 in 2011 to 3482 in 2017, a 30% decline. Among symptomatic patients, there was a 25% decline, the number of CEAs falling from 4270 to 3217. In asymptomatic patients, there were 722 CEAs performed in 2011 and 265 in 2017, a 63% decline. CEAs per 100 000 adults within all regions declined over time but the size of change varied across the regions (range, 1.7–5.5 per 100 000). The regional numbers of CEAs per year were associated with changes in the regional stroke incidence, the proportion of CEAs performed in asymptomatic patients, and the number of hospitals performing CEA. Conclusions— This population-based study revealed a 63% decline in CEAs among asymptomatic patients between 2011 and 2017, possibly because of changing attitudes in the role of CEA. Reasons for the 25% decline in CEAs among symptomatic patients are unclear as UK guidelines on CEA have not changed for these patients. Whether the proportion of symptomatic patients with 50% to 99% ipsilateral stenosis has changed requires investigation.

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 and aims Individual-level socioeconomic deprivation is associated with an increased risk of adverse patient outcomes following cardiovascular disease interventions, but the role of area-level socioeconomic circumstances as a predictor for treatment outcomes is unclear. We have examined the association of neighbourhood socioeconomic deprivation with risks of major lower limb amputation and death following surgical and endovascular lower limb revascularisation due to peripheral artery disease (PAD). Methods Patients aged 50+ years who underwent surgical or endovascular lower limb revascularisation for PAD were identified from Hospital Episode Statistics, a nationwide hospital data warehouse in England. Major amputations and deaths within a year of revascularisation were ascertained from HES and national mortality register, respectively. Index of Multiple Deprivation (IMD) was used to measure neighbourhood deprivation. Flexible parametric competing risks models were used to estimate sub-distribution hazard ratios (SHRs) for amputation and death. Results In all, 65,806 patients underwent endovascular and 20,072 underwent surgical revascularisation. The covariate-adjusted 1-year risk of major amputation was higher among patients from the most deprived compared to least deprived neighbourhoods following endovascular revascularisation (SHR: 1.24, 95% confidence interval, CI:1.10 to 1.38) and surgical revascularisation (SHR:1.28, 95% CI: 1.09 to 1.51). The risk of death was higher in most deprived compared to the least deprived neighbourhoods following both procedures. Conclusions We found a consistent association between neighbourhood deprivation and amputation and death outcomes following lower limb revascularisation for PAD. These findings suggest there may be opportunities for targeted interventions to improve care of PAD patients in deprived neighbourhoods.

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.

BackgroundAdverse psychosocial working environments characterized by job strain (the combination of high demands and low control at work) are associated with an increased risk of depressive symptoms among employees, but evidence on clinically diagnosed depression is scarce. We examined job strain as a risk factor for clinical depression.MethodWe identified published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium. Summary estimates of the association were obtained using random-effects models. Individual-level data analyses were based on a pre-published study protocol.ResultsWe included six published studies with a total of 27 461 individuals and 914 incident cases of clinical depression. From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression. Job strain was associated with an increased risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47–2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04–1.55). Further individual participant analyses showed a similar association across sociodemographic subgroups and after excluding individuals with baseline somatic disease. The association was unchanged when excluding individuals with baseline depressive symptoms (RR = 1.25, 95% CI 0.94–1.65), but attenuated on adjustment for a continuous depressive symptoms score (RR = 1.03, 95% CI 0.81–1.32).ConclusionsJob strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

Aims Clinical experience suggests that atherosclerotic disease is common in individuals with coeliac disease, but epidemiological studies have had contradicting findings. To summarise the currently available evidence, we systematically reviewed and analysed observational studies of the association of coeliac disease or dermatitis herpetiformis with coronary heart disease (CHD) or stroke. Data synthesis We searched for studies comparing CHD or stroke outcomes with individuals with and without coeliac disease or dermatitis herpetiformis. Three investigators independently searched electronic databases, identified relevant studies and extracted data. Study-specific results were combined in random-effects meta-analyses, and heterogeneity was quantified using the I 2 statistic and meta-regression. Twenty-one studies were included in our systematic review and 18 in the meta-analyses. For CHD, the pooled hazard ratio for incident disease was 1.05 (95% confidence interval (CI): 0.93, 1.19) and the overall standardised mortality ratio was 1.21 (0.99, 1.49). For stroke and brain haemorrhage, the corresponding estimates were 1.10 (95% CI: 1.00, 1.21) and 1.43 (0.97, 2.10), respectively. There was moderate to considerable heterogeneity among the study-specific estimates. In addition, many estimates were based on small numbers of outcomes and they had limitations in terms of adjustment for potential confounders. Conclusion Our meta-analyses lend some support to an association between coeliac disease and CHD or cerebrovascular disease, but the evidence base was heterogeneous and had limitations. Our systematic review highlighted a need in this area for adequately powered prospective studies with appropriate adjustment for potentially confounding factors.

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.

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 Availability and diversity of lower limb revascularisation procedures have increased in in the past decade, co-inciding with the reconfiguration of vascular services in the United Kingdom. The aim of our study was to investigate whether these developments in care have translated to improvements in patient outcomes. Methods We used data from Hospital Episode Statistics (HES) to identify patients who underwent endovascular or surgical (endarterectomy, profundaplasty or bypass) lower limb revascularisation for infrainguinal peripheral arterial disease (PAD) in England in 2006–2013. Major lower limb amputations and deaths were ascertained from HES and Office for National Statistics mortality register. Associations of revascularisation procedures with amputation and death outcomes were investigated using Fine-Grey competing risks regression, with adjustment for patient age, sex and comorbidity score. We examined the possible impact of patient selection by stratifying our analyses by indication for revascularisation (intermittent claudication only; severe limb ischaemia without tissue loss; severe limb ischaemia with ulceration; severe limb ischaemia with gangrene). Results Over the 8 year study period the overall number of endovascular revascularisations increased and the number of surgical procedures decreased: the evidence for this trend was the clearest among patients with the most severe underlying disease (severe limb ischaemia with ulceration or gangrene). The 1 year risk of major amputation reduced from 5.9% (in 2006–07) to 5.5% (in 2012–13) following endovascular evascularization and from 10.8% (2006–07) to 7.4% (2012–13) following surgical procedures (p Discussion Our findings suggest that patient outcomes following lower limb revascularisation have improved during a period of centralisation and specialisation of vascular services in the United Kingdom, despite higher morbidity and an increasing proportion of patients treated for the severe end of the PAD spectrum.

Overtime work and long working hours are associated with an increased risk of many adverse health outcomes, such as coronary heart disease and stroke. However, the relationship of excess working hours with incident cancer is unclear. To address this gap in the knowledge, we examined the association between weekly working hours and cancer risk using individual-participant data from 12 prospective studies from Denmark, Finland, Germany, Sweden, the Netherlands and the UK.Our analyses were based on data from 116 462 working men and women, who were free of cancer at study baseline. Incident cancers were ascertained from national cancer, hospitalisation and death registers. Weekly working hours were self-reported. During a follow-up ranging from 4 to 22 years, 4 371 participants were diagnosed with cancer (n colorectal cancer: 393, n lung cancer: 247, n breast cancer: 833, n prostate cancer: 534). Compared to standard working time (35–40 hours/week), working >55 hours/week was not associated with the overall cancer incidence (multivariable-adjusted HR (95% CI): 1.00 (0.85, 1.16). Similarly, working hours were unrelated to incident colorectal, lung and prostate cancers. Compared to standard hours, working >55 hours/week was associated with 1.60-fold (95% CI: 1.12–2.29) risk of female breast cancer. This association was independent of age, socioeconomic position, shift- and night-time work and lifestyle factors, but it may have been influenced by residual confounding from parity. To our knowledge, ours is the largest investigation of this topic to-date and the first to examine the association of working hours with the overall cancer risk and the risk of specific cancers. Our findings suggest that working long hours is not a risk factor for cancer in general, or lung, colorectal or prostate cancers in particular. The observed association with breast cancer would warrant further research.

BACKGROUND: Job insecurity has been associated with certain health outcomes. We examined the role of job insecurity as a risk factor for incident diabetes. METHODS: We used individual participant data from 8 cohort studies identified in 2 open-access data archives and 11 cohort studies participating in the Individual-Participant-Data Meta-analysis in Working Populations Consortium. We calculated study-specific estimates of the association between job insecurity reported at baseline and incident diabetes over the follow-up period. We pooled the estimates in a meta-analysis to produce a summary risk estimate. RESULTS: The 19 studies involved 140 825 participants from Australia, Europe and the United States, with a mean follow-up of 9.4 years and 3954 incident cases of diabetes. In the preliminary analysis adjusted for age and sex, high job insecurity was associated with an increased risk of incident diabetes compared with low job insecurity (adjusted odds ratio [OR] 1.19, 95% confidence interval [CI] 1.09-1.30). In the multivariable-adjusted analysis restricted to 15 studies with baseline data for all covariates (age, sex, socioeconomic status, obesity, physical activity, alcohol and smoking), the association was slightly attenuated (adjusted OR 1.12, 95% CI 1.01-1.24). Heterogeneity between the studies was low to moderate (age- and sex-adjusted model: I2 = 24%, p = 0.2; multivariable-adjusted model: I2 = 27%, p = 0.2). In the multivariable-adjusted analysis restricted to high-quality studies, in which the diabetes diagnosis was ascertained from electronic medical records or clinical examination, the association was similar to that in the main analysis (adjusted OR 1.19, 95% CI 1.04-1.35). INTERPRETATION: Our findings suggest that self-reported job insecurity is associated with a modest increased risk of incident diabetes. Health care personnel should be aware of this association among workers reporting job insecurity.

Objective Guidelines recommend that patients suffering an ischaemic transient ischaemic attack (TIA) or stroke caused by carotid artery stenosis should undergo carotid endarterectomy (CEA) within 14 days. Method The degree to which UK vascular units met this standard was examined and whether rapid interventions were associated with procedural risks. The study analysed patients undergoing CEA between January 2009 and December 2014 from 100 UK NHS hospitals. Data were collected on patient characteristics, intervals of time from symptoms to surgery, and 30-day postoperative outcomes. The relationship between outcomes and time from symptom to surgery was evaluated using multilevel multivariable logistic regression. Results In 23,235 patients, the median time from TIA/stroke to CEA decreased over time, from 22 days (IQR 10–56) in 2009 to 12 days (IQR 7–26) in 2014. The proportion of patients treated within 14 days increased from 37% to 58%. This improvement was produced by shorter times across the care pathway: symptoms to referral, from medical review to being seen by a vascular surgeon, and then to surgery. The spread of the median time from symptom to surgery among NHS hospitals shrank between 2009 and 2013 but then grew slightly. Low-, medium-, and high-volume NHS hospitals all improved their performance similarly. Performing CEA within 48 h of symptom onset was associated with a small increase in the 30-day stroke and death rate: 3.1% (0–2 days) compared with 2.0% (3–7 days); adjusted odds ratio 1.64 (95% CI 1.04–2.59) but not with longer delays. Conclusions The delay from symptom to CEA in symptomatic patients with ipsilateral 50–99% carotid stenoses has reduced substantially, although 42% of patients underwent CEA after the recommended 14 days. The risk of stroke after CEA was low, but there may be a small increase in risk during the first 48 h after symptoms.

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

Our aim was to investigate whether the duration of breastfeeding, at all or exclusively, is associated with educational achievement at age 5. We used data from a prospective, population-based UK cohort study, the Millennium Cohort Study (MCS). 5489 children from White ethnic background born at term in 2000-2001, attending school in England in 2006, were included in our analyses. Educational achievement was measured using the Foundation Stage Profile (FSP), a statutory assessment undertaken by teachers at the end of the child's first school year. Breastfeeding duration was ascertained from interviews with the mother when the child was 9 months old. We used modified Poisson's regression to model the association of breastfeeding duration with having reached a good level of achievement overall (≥78 overall points and ≥6 in 'personal, social and emotional development' and 'communication, language and literacy' points) and in specific areas (≥6 points) of development. Children who had been breastfed for up to 2 months were more likely to have reached a good level of overall achievement [adjusted rate ratio (RR): 1.09, 95% confidence interval (CI): 1.01, 1.19] than never breastfed children. This association was more marked in children breastfed for 2-4 months (adjusted RR: 1.17, 95% CI: 1.07, 1.29) and in those breastfed for longer than 4 months (adjusted RR: 1.16, 95% CI: 1.07, 1.26). The associations of exclusive breastfeeding with the educational achievement were similar. Our findings suggest that longer duration of breastfeeding, at all or exclusively, is associated with better educational achievement at age 5. © 2012 John Wiley and Sons Ltd.

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.

Our aim was to systematically review the epidemiologic evidence for an association of circulating interleukin-6 (IL-6), an inflammatory cytokine and cancer. We systematically searched electronic databases Embase, Medline and Web of Science for the studies of circulating IL-6 and any form of cancer. We identified and reviewed 189 discrete studies, consisting of 177 prevalent studies and three prospective studies. Cancer patients' IL-6 concentrations were higher than healthy controls' in most studies, but the results of investigations comparing IL-6 in cancer patients and individuals with benign diseases were less consistent. Due to the small number of prospective studies it is impossible to determine whether IL-6 is causally related to cancer. Large prospective studies of circulating IL-6 or studies using the functional variants of the IL-6 gene as instruments for circulating IL-6 concentrations would provide information on possible aetiological links between IL-6 and malignancy.

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)

Celiac disease, an autoimmune disease induced by dietary gluten, is associated with metabolic bone disorders, such as low bone mineral density. However, it is unclear whether this translates into an association between celiac disease and such hard clinical outcomes as bone fractures.To systematically review and pool the evidence for the relationship of celiac disease with prevalence and incidence of bone fractures.We systematically searched Pubmed, Scopus, Web of Science, and Cochrane Library in January 2014 for studies of celiac disease and bone fractures.Observational studies of any design, in which bone fracture outcomes were compared in individuals with and without celiac disease were included.Two investigators independently extracted results from eligible studies.In the meta-analyses of case-control and cross-sectional studies, bone fractures were almost twice as common in individuals with a clinically diagnosed celiac disease as in those without the disease. In the meta-analyses of prospective studies, celiac disease at baseline was associated with a 30% increase (95% confidence interval [CI]: 1.14, 1.50) in the risk of any fracture and a 69% increase in the risk of hip fracture (95% CI: 1.10, 2.59). The two studies of unrecognized celiac disease (elevated circulating concentrations of celiac disease-specific autoantibodies but no celiac disease diagnosis) had contradicting findings.Our findings suggest that clinically diagnosed celiac disease and bone fractures co-occur and that celiac disease was associated with an increased risk of hip fractures as well as fractures in general. Further research would be needed to determine whether unrecognized celiac disease is associated with the risk of bone fractures.

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: 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.

Guidelines recommend that patients suffering an ischaemic transient ischaemic attack (TIA) or stroke caused by carotid artery stenosis should undergo carotid endarterectomy (CEA) within 14 days. : The degree to which UK vascular units met this standard was examined and whether rapid interventions were associated with procedural risks. The study analysed patients undergoing CEA between January 2009 and December 2014 from 100 UK NHS hospitals. Data were collected on patient characteristics, intervals of time from symptoms to surgery, and 30-day postoperative outcomes. The relationship between outcomes and time from symptom to surgery was evaluated using multilevel multivariable logistic regression. : In 23,235 patients, the median time from TIA/stroke to CEA decreased over time, from 22 days (IQR 10-56) in 2009 to 12 days (IQR 7-26) in 2014. The proportion of patients treated within 14 days increased from 37% to 58%. This improvement was produced by shorter times across the care pathway: symptoms to referral, from medical review to being seen by a vascular surgeon, and then to surgery. The spread of the median time from symptom to surgery among NHS hospitals shrank between 2009 and 2013 but then grew slightly. Low-, medium-, and high-volume NHS hospitals all improved their performance similarly. Performing CEA within 48 h of symptom onset was associated with a small increase in the 30-day stroke and death rate: 3.1% (0-2 days) compared with 2.0% (3-7 days); adjusted odds ratio 1.64 (95% CI 1.04-2.59) but not with longer delays. : The delay from symptom to CEA in symptomatic patients with ipsilateral 50-99% carotid stenoses has reduced substantially, although 42% of patients underwent CEA after the recommended 14 days. The risk of stroke after CEA was low, but there may be a small increase in risk during the first 48 h after symptoms.

Katriina Heikkila, Solja T. Nyberg and Mika Kivimaki respond to a letter to the editor submitted in response to their article "Job Strain and Health-Related Lifestyle: Findings From an Individual Participant Meta-Analysis of 118,000 Working Adults" in a 2013 issue.

Aim Our aim was to examine whether breast feeding is associated with behavioural development in children aged 5 years. Methods We used data from a large, prospective, nationally representative UK cohort, the Millennium Cohort Study. Breast feeding was ascertained from parent-interviews at baseline and child behaviour from parent-rated outcome, the Strengths and Difficulties Questionnaire (SDQ). Our analyses included 10 037 mother-child pairs with data on breast feeding, SDQ and potential confounders. 9525 of the children were born at term and 512 were preterm. We used logistic regression models to investigate the associations of breast feeding duration with abnormal parent-rated SDQ total and sub-scores at age five in term and preterm children separately. Results Overall, abnormal SDQ scores were less common in breast fed than formula-fed children. Term children breast fed for four months or longer had lower odds of an abnormal total SDQ score (multivariable-adjusted OR compared to never breast fed children: 0.65, 95% CI 0.52 to 0.82). This effect was similar for all the SDQ sub-scores. In preterm children prolonged breast feeding was generally associated with lower odds of abnormal SDQ total and sub-scores 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 Our findings suggest that, at least in term children, prolonged breast feeding is associated with having fewer parent-rated behavioural problems at the age of 5 years.