Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.

Preterm birth and the risk of multimorbidity in adolescence: a multiregister-based cohort study.

BACKGROUND: Multimorbidity affects people of all ages, but the risk factors of multimorbidity in adolescence are unclear. The aim of this study was to examine preterm birth (<37 weeks) as a shared risk factor for multiple health outcomes and the role of gestational age (degree of prematurity) in the development of increasingly complex multimorbidity (two, three, or four health outcomes) in adolescence (age 10-18 years). METHODS: We used population-wide data from Finland (1 187 610 adolescents born 1987-2006) and Norway (555 431 adolescents born 1998-2007). Gestational age at birth was ascertained from medical birth registers and categorised as 23-27 weeks (extremely preterm), 28-31 weeks (very preterm), 32-33 weeks (moderately preterm), 34-36 weeks (late preterm), 37-38 weeks (early term), 39-41 weeks (term, reference category) and 42-44 weeks (post-term). Children who died or emigrated before their 10th birthday, and those with missing or implausible data on gestational age, birthweight, or covariates, were excluded. Health outcomes at age 10-18 years were ascertained from specialised health care and mortality registers. We calculated hazard ratios (HRs) and population attributable fractions (PAFs) with 95% CIs for multiple health outcomes during adolescence. FINDINGS: Individuals were followed up from age 10 to 18 years (mean follow-up: 6 years, SD: 3 years). Preterm birth was associated with increased risks of 20 hospital-treated malignant, cardiovascular, endocrinological, neuropsychiatric, respiratory, genitourinary, and congenital health outcomes, after correcting for multiple testing and ignoring small effects (HR <1·2). Confounder-adjusted HRs comparing preterm with term-born adolescents were 2·29 (95% CI 2·19-2·39) for two health outcomes (PAF 9·0%; 8·3-9·6), and 4·22 (3·66-4·87) for four health outcomes (PAF 22·7%; 19·4-25·8) in the Finnish data. Results in the Norwegian data showed a similar pattern. We observed a consistent dose-response relationship between an earlier gestational age and elevated risks of increasingly complex multimorbidity in both datasets. INTERPRETATION: Preterm birth is associated with increased risks of diverse multimorbidity patterns at age 10-18 years. Adolescents with a preterm-born background could benefit from diagnostic vigilance directed at multimorbidity and a multidisciplinary approach to health care. FUNDING: European Union Horizon 2020, Academy of Finland, Foundation for Pediatric Research, Sigrid Jusélius Foundation, Signe and Ane Gyllenberg Foundation.

Preterm birth and asthma and COPD in adulthood: a nationwide register study from two Nordic countries.

BACKGROUND: Preterm birth affects lungs in several ways but 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. METHODS: We used nationwide registry 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 for 2005-2016 and in Norway for 2008-2017. We used logistic regression to estimate odds ratios (ORs) for having a care episode with either disease outcome. RESULTS: Odds of any obstructive airway disease in adulthood for those born at <28 or 28-31 completed weeks were 2-3-fold of those born full term (39-41 completed weeks), persisting after adjustments. For individuals born at 32-33, 34-36 or 37-38 weeks, the odds were 1.1- to 1.5-fold. Associations were similar in the Finnish and the Norwegian data and among people aged 18-29 and 30-50 years. For COPD at age 30-50 years, the OR was 7.44 (95% CI 3.49-15.85) for those born at <28 weeks, 3.18 (95% CI 2.23-4.54) for those born at 28-31 weeks and 2.32 (95% CI 1.72-3.12) for those born at 32-33 weeks. Bronchopulmonary dysplasia in infancy increased the odds further for those born at <28 and 28-31 weeks. CONCLUSION: Preterm birth is a risk factor for asthma and COPD in adulthood. The high odds of COPD call for diagnostic vigilance when adults born very preterm present with respiratory symptoms.

Working life sequences over the life course among 9269 women and men in Sweden; a prospective cohort study.

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.

Clustering of disability pension and socioeconomic disadvantage in Sweden: a geospatial analysis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clustering of social disadvantage with attention-deficit/hyperactivity disorder in young adults: A register-based study in Sweden.

The clustering of social disadvantage with attention-deficit/hyperactivity disorder (ADHD) in young adulthood is not well understood. We examined the clustering of ADHD with low educational attainment and unemployment in young adulthood; whether such clustering is stronger when unemployment is prolonged; and whether further clustering of disability pensioning, low education and unemployment occurs among those with ADHD. Data were obtained from Swedish health, demographic and social security registers from which 8,990 individuals with recorded ADHD diagnoses at the age of 10-35 and their 44,387 matched referents 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. 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. The results suggest that low education and unemployment appear to cluster remarkably with ADHD among young adults, more so among women and when unemployment is prolonged.

Preterm birth and the risk of chronic disease multimorbidity in adolescence and early adulthood: A population-based cohort study.

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.

C-reactive protein and temperament: An instrumental variable analysis.

BACKGROUND: Temperament is associated with circulating inflammatory biomarkers, such as C-reactive protein (CRP), which has been associated with various health conditions, including depression. This study aims to investigate whether genetic disposition for increased circulating CRP concentration may influence temperament over the life-course. METHODS: Using a longitudinal cohort that began in 1980-the Cardiovascular Risk in Young Finns Study (YFS)-we included 920 participants (59.8% female) aged 3-12 years old at baseline (childhood), and the same participants again at ages 30-39 years old (adulthood) in this study. We used both ordinary least-squares regression (OLS linear regression) and instrumental variable (IV) regression to assess associations between CRP concentration and temperament dimensions (negative emotionality, activity, and sociability). To represent genetically determined risk for increase in circulating CRP concentration, we calculated a weighted genetic risk score (GRS) which reflects risk for increased circulating CRP concentration. RESULTS: In OLS linear regression analyses, we found that increased circulating CRP concentration in childhood was associated with slightly higher scores for sociability in childhood (19% increase, CI â€‹= â€‹7-32%) and adulthood (13% increase, CI â€‹= â€‹2-27%), and lower activity scores in adulthood (15% decrease, CI â€‹= â€‹3-25%). For all IV regressions, there were no apparent associations between GRS and temperament in either childhood or adulthood (all p>0.3). The Durbin-Wu-Hausman test for endogeneity produced p-values (all>0.05) that suggest there is no evidence for disagreement between the OLS and IV estimates. CONCLUSIONS: We found no clear evidence for an association of GRS for elevated CRP with childhood or adulthood emotionality, activity, or sociability, although circulating CRP was associated with some of these traits.

Work Participation among Women and Men in Sweden: A Register Study of 8.5 Million Individuals.

Observational research studies from various countries suggest that women's working patterns across the life course are often fragmented compared to men's. The aim of our investigation was to use nationwide register data from Sweden to examine the extent to which generation and time of entry to the work force explain the sex differences in work participation across the life course. Our analyses were based on individual-level data on 4,182,581 women and 4,279,571 men, who were 19-69 years old and resident in Sweden in 1995, 2000, 2005, 2010, or 2015. Data on income and number of net days on disability pension, obtained from multiple linked registers, were used to ascertain each individual's main activity (in paid work, on disability pension, and not in paid work) each year. Years in paid work and on disability pension were calculated as the sums of years spent in either of these states from age 19 to 69 years. We used negative binomial regression to model the associations of generation and baseline year with years in paid work and years on disability pension. All models were run separately for women and men, with the duration of follow-up constrained to one, to account for the different follow-up times between individuals. Overall, the number of years in paid work across the life course was larger among men than women, and men entered into the workforce earlier. The difference between women and men was similar across generations and time periods. Adjustment for education, income, number of children aged <18 years living at home, country of birth, and the type of residential area had minimal impact on the estimates. Our findings suggest that women spend fewer years in paid work across the life course than men, highlighting the need for continued efforts to close the gender gap in work participation.

Association of neighbourhood deprivation with risks of major amputation and death following lower limb revascularisation.

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.

Association of Healthy Lifestyle With Years Lived Without Major Chronic Diseases.

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 116 043 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 116 043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 383 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 < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex. Conclusions and Relevance: In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.

Job Strain as a Risk Factor for Peripheral Artery Disease: A Multi-Cohort Study.

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 τ2, I2, 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 (τ2=0.0427, I2: 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.

Changing Patterns of Carotid Endarterectomy Between 2011 and 2017 in England.

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.

Physical activity and peripheral artery disease: Two prospective cohort studies and a systematic review.

BACKGROUND AND AIMS: Physical activity is a modifiable risk factor for cardiovascular disease and an important therapy in individuals with intermittent claudication. However, its role in the development of peripheral artery disease (PAD) is unclear. We have examined the evidence of the association between physical activity and development of PAD. METHODS: We searched PubMed, EMBASE and CINAHL Plus in August 2018 for original studies of physical activity and PAD. Studies reporting prevalence or incidence of PAD by categories of physical activity (an amount of activity per unit of time) were included. In addition, we analysed unpublished individual-level data from two register-linked cohort studies, Finnish Public Sector Study (n = 63,924) and Whitehall II (n = 10,200). Due to heterogeneity in the assessment of physical activity and PAD, we provide a qualitative synthesis of the findings. RESULTS: Evidence from 18 studies (15 cross-sectional/case-control and 7 prospective studies) of the association between physical activity and PAD in total of 152,188 participants, including 3971 PAD patients, suggests that individuals with a diagnosis or clinical findings of PAD were less physically active, regardless of whether activity was self-reported or measured using accelerometers. The findings from the longitudinal studies point to more intense physical activity being associated with lower odds of developing PAD; however, the study-specific findings lacked power to precisely estimate this relationship. CONCLUSIONS: Individuals with PAD were less physically active than those without PAD. The longitudinal findings suggest that physical activity decreases the risk of PAD, although better powered studies are needed to confirm this.

Obesity and loss of disease-free years owing to major non-communicable diseases: a multicohort study.

BACKGROUND: Obesity increases the risk of several chronic diseases, but the extent to which the obesity-related loss of disease-free years varies by lifestyle category and across socioeconomic groups is unclear. We estimated the number of years free from major non-communicable diseases in adults who are overweight and obese, compared with those who are normal weight. METHODS: We pooled individual-level data on body-mass index (BMI) and non-communicable diseases from men and women with no initial evidence of these diseases in European cohort studies from the Individual-Participant-Data Meta-Analysis in Working Populations consortium. BMI was assessed at baseline (1991-2008) and non-communicable diseases (incident type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease) were ascertained via linkage to records from national health registries, repeated medical examinations, or self-report. Disease-free years from age 40 years to 75 years associated with underweight (BMI <18·5 kg/m2), overweight (≥25 kg/m2 to <30 kg/m2), and obesity (class I [mild] ≥30 kg/m2 to <35 kg/m2; class II-III [severe] ≥35 kg/m2) compared with normal weight (≥18·5 kg/m2 to <25 kg/m2) were estimated. FINDINGS: Of 137 503 participants from ten studies, we excluded 6973 owing to missing data and 10 349 with prevalent disease at baseline, resulting in an analytic sample of 120 181 participants. Of 47 127 men, 211 (0·4%) were underweight, 21 468 (45·6%) normal weight, 20 738 (44·0%) overweight, 3982 (8·4%) class I obese, and 728 (1·5%) class II-III obese. The corresponding numbers among the 73 054 women were 1493 (2·0%), 44 760 (61·3%), 19 553 (26·8%), 5670 (7·8%), and 1578 (2·2%), respectively. During 1 328 873 person-years at risk (mean follow-up 11·5 years [range 6·3-18·6]), 8159 men and 8100 women developed at least one non-communicable disease. Between 40 years and 75 years, the estimated number of disease-free years was 29·3 (95% CI 28·8-29·8) in normal-weight men and 29·4 (28·7-30·0) in normal-weight women. Compared with normal weight, the loss of disease-free years in men was 1·8 (95% CI -1·3 to 4·9) for underweight, 1·1 (0·7 to 1·5) for overweight, 3·9 (2·9 to 4·9) for class I obese, and 8·5 (7·1 to 9·8) for class II-III obese. The corresponding estimates for women were 0·0 (-1·4 to 1·4) for underweight, 1·1 (0·6 to 1·5) for overweight, 2·7 (1·5 to 3·9) for class I obese, and 7·3 (6·1 to 8·6) for class II-III obese. The loss of disease-free years associated with class II-III obesity varied between 7·1 and 10·0 years in subgroups of participants of different socioeconomic level, physical activity level, and smoking habit. INTERPRETATION: Mild obesity was associated with the loss of one in ten, and severe obesity the loss of one in four potential disease-free years during middle and later adulthood. This increasing loss of disease-free years as obesity becomes more severe occurred in both sexes, among smokers and non-smokers, the physically active and inactive, and across the socioeconomic hierarchy. FUNDING: NordForsk, UK Medical Research Council, US National Institute on Aging, Academy of Finland, Helsinki Institute of Life Science, and Cancer Research UK.

Long working hours and depressive symptoms: systematic review and meta-analysis of published studies and unpublished individual participant data.

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.

Improving 1-Year Outcomes of Infrainguinal Limb Revascularization: Population-Based Cohort Study of 104 000 Patients in England.

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.

Long working hours as a risk factor for atrial fibrillation: a multi-cohort study.

AIMS: Studies suggest that people who work long hours are at increased risk of stroke, but the association of long working hours with atrial fibrillation, the most common cardiac arrhythmia and a risk factor for stroke, is unknown. We examined the risk of atrial fibrillation in individuals working long hours (≥55 per week) and those working standard 35-40 h/week. METHODS AND RESULTS: In this prospective multi-cohort study from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium, the study population was 85 494 working men and women (mean age 43.4 years) with no recorded atrial fibrillation. Working hours were assessed at study baseline (1991-2004). Mean follow-up for incident atrial fibrillation was 10 years and cases were defined using data on electrocardiograms, hospital records, drug reimbursement registers, and death certificates. We identified 1061 new cases of atrial fibrillation (10-year cumulative incidence 12.4 per 1000). After adjustment for age, sex and socioeconomic status, individuals working long hours had a 1.4-fold increased risk of atrial fibrillation compared with those working standard hours (hazard ratio = 1.42, 95% CI = 1.13-1.80, P = 0.003). There was no significant heterogeneity between the cohort-specific effect estimates (I2 = 0%, P = 0.66) and the finding remained after excluding participants with coronary heart disease or stroke at baseline or during the follow-up (N = 2006, hazard ratio = 1.36, 95% CI = 1.05-1.76, P = 0.0180). Adjustment for potential confounding factors, such as obesity, risky alcohol use and high blood pressure, had little impact on this association. CONCLUSION: Individuals who worked long hours were more likely to develop atrial fibrillation than those working standard hours.