C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.

A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.

Genetic contribution to disease-course severity and progression in the SUPER-Finland study, a cohort of 10,403 individuals with psychotic disorders.

Genetic factors contribute to the susceptibility of psychotic disorders, but less is known how they affect psychotic disease-course development. Utilizing polygenic scores (PGSs) in combination with longitudinal healthcare data with decades of follow-up we investigated the contributing genetics to psychotic disease-course severity and diagnostic shifts in the SUPER-Finland study, encompassing 10 403 genotyped individuals with a psychotic disorder. To longitudinally track the study participants' past disease-course severity, we created a psychiatric hospitalization burden metric using the full-coverage and nation-wide Finnish in-hospital registry (data from 1969 and onwards). Using a hierarchical model, ranking the psychotic diagnoses according to clinical severity, we show that high schizophrenia PGS (SZ-PGS) was associated with progression from lower ranked psychotic disorders to schizophrenia (OR = 1.32 [1.23-1.43], p = 1.26e-12). This development manifested already at psychotic illness onset as a higher psychiatric hospitalization burden, the proxy for disease-course severity. In schizophrenia (n = 5 479), both a high SZ-PGS and a low educational attainment PGS (EA-PGS) were associated with increased psychiatric hospitalization burden (p = 1.00e-04 and p = 4.53e-10). The SZ-PGS and the EA-PGS associated with distinct patterns of hospital usage. In individuals with high SZ-PGS, the increased hospitalization burden was composed of longer individual hospital stays, while low EA-PGS associated with shorter but more frequent hospital visits. The negative effect of a low EA-PGS was found to be partly mediated via substance use disorder, a major risk factor for hospitalizations. In conclusion, we show that high SZ-PGS and low EA-PGS both impacted psychotic disease-course development negatively but resulted in different disease-course trajectories.

SARS-CoV-2 Infection of Human Neurons Is TMPRSS2 Independent, Requires Endosomal Cell Entry, and Can Be Blocked by Inhibitors of Host Phosphoinositol-5 Kinase.

2019 coronavirus disease (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to respiratory illness, COVID-19 patients exhibit neurological symptoms lasting from weeks to months (long COVID). It is unclear whether these neurological manifestations are due to an infection of brain cells. We found that a small fraction of human induced pluripotent stem cell (iPSC)-derived neurons, but not astrocytes, were naturally susceptible to SARS-CoV-2. Based on the inhibitory effect of blocking antibodies, the infection seemed to depend on the receptor angiotensin-converting enzyme 2 (ACE2), despite very low levels of its expression in neurons. The presence of double-stranded RNA in the cytoplasm (the hallmark of viral replication), abundant synthesis of viral late genes localized throughout infected cells, and an increase in the level of viral RNA in the culture medium (viral release) within the first 48 h of infection suggested that the infection was productive. Productive entry of SARS-CoV-2 requires the fusion of the viral and cellular membranes, which results in the delivery of the viral genome into the cytoplasm of the target cell. The fusion is triggered by proteolytic cleavage of the viral surface spike protein, which can occur at the plasma membrane or from endosomes or lysosomes. We found that SARS-CoV-2 infection of human neurons was insensitive to nafamostat and camostat, which inhibit cellular serine proteases, including transmembrane serine protease 2 (TMPRSS2). Inhibition of cathepsin L also did not significantly block infection. In contrast, the neuronal infection was blocked by apilimod, an inhibitor of phosphatidyl-inositol 5 kinase (PIK5K), which regulates early to late endosome maturation. IMPORTANCE COVID-19 is a disease caused by the coronavirus SARS-CoV-2. Millions of patients display neurological symptoms, including headache, impairment of memory, seizures, and encephalopathy, as well as anatomical abnormalities, such as changes in brain morphology. SARS-CoV-2 infection of the human brain has been documented, but it is unclear whether the observed neurological symptoms are linked to direct brain infection. The mechanism of virus entry into neurons has also not been characterized. Here, we investigated SARS-CoV-2 infection by using a human iPSC-derived neural cell model and found that a small fraction of cortical-like neurons was naturally susceptible to infection. The productive infection was ACE2 dependent and TMPRSS2 independent. We also found that the virus used the late endosomal and lysosomal pathway for cell entry and that the infection could be blocked by apilimod, an inhibitor of cellular PIK5K.

Changes in occupational class differences in leisure-time physical activity and the contribution of retirement.

Occupational class differences in leisure-time physical activity (LTPA) are well recognized. Less is known about how these differences develop as individuals age, and how retirement is associated with this change. We investigated how occupational class differences in LTPA change in a cohort over a 15-17 years follow-up. We further examined, how the transition into mandatory or disability retirement contributed to the change in LTPA levels and occupational class differences. We used the data from the Helsinki Health Study surveying the aging City of Helsinki employees. In all, 8773 individuals were included in the analyses. We evaluated LTPA levels using weekly metabolic equivalent task (MET) hours and used generalized linear mixed effect models (GLMM) to estimate the development of LTPA levels. Commuting was included in the LTPA measure. Occupational class differences in LTPA emerged and widened during the follow-up. The physical activity levels decreased in the lower occupational class and slightly increased in the higher occupational class, resulting in a difference of 4.3 MET-hours at the end of follow-up, accounting for 50 min of brisk walking per week. The occupational class differences emerged during transition into mandatory retirement and persisted after this. Transition into disability retirement temporarily widened the occupational class differences in LTPA levels, but the differences diminished during the follow-up. Research on interventions to counteract the declining LTPA is needed to discover ways to prevent the widening of occupational health disparities during aging. The transition into old-age retirement could be an optimal period for focusing these interventions.

Trajectories of CVD medication after statutory retirement: contributions of pre-retirement sociodemographic, work and health-related factors: a register study in Finland.

BACKGROUND: Cardiovascular diseases (CVDs) are prevalent in older people, but few studies focus on developmental patterns in CVD medication directly after transition to statutory retirement. We thus aimed to identify trajectories of CVD medication after retirement, and their sociodemographic, work and health-related determinants. METHODS: We used complete register data of former employees of the City of Helsinki, Finland. All who reached their statutory retirement in 2000-2013, with five-year follow-up data (n = 6,505, 73% women), were included. Trajectories of CVD medication were identified with group-based trajectory modelling using data from Finnish Social Insurance Institution's reimbursement register. Sociodemographic, work and health-related determinants of trajectory group membership were analysed using multinomial logistic regression. RESULTS: Six trajectories of CVD medication were distinguished: "constant low" (35%), "late increase" (6%), "early increase" (5%), "constant high" (39%), "high and decreasing " (8%), and "low and decreasing" (7%). The majority (74%) of the retirees fell into the "constant low" and "constant high" categories. Lower occupational class and increased pre-retirement sickness absence were associated with the "constant high" trajectory. Further, those with lower educational attainment were more prone to be in the "early increase" trajectory. CONCLUSIONS: Individuals in lower socioeconomic positions or with a higher number of pre-retirement sickness absence may be considered at higher risk and might benefit from early interventions, e.g. lifestyle interventions and interventions targeting working conditions, or more frequent monitoring.

Life-course socioeconomic circumstances in acute, chronic and disabling pain among young employees: a double suffering.

BACKGROUND: Pain is known to be socioeconomically patterned and associated with disability. However, knowledge is scarce concerning life-course socioeconomic circumstances and pain among young adults. Our aim was to examine the associations of childhood and current socioeconomic circumstances with acute pain and chronic pain with low and high disability levels among young Finnish municipal employees. METHODS: We analysed questionnaire data retrieved from the Young Helsinki Health Study (n=4683) covering 18-39-year-old employees of the City of Helsinki, Finland. We included multiple indicators of childhood and current socioeconomic circumstances and examined their associations with acute pain and with chronic pain with low and high disability levels. The level of chronic pain-related disability was assessed by the chronic pain grade questionnaire. Multinomial logistic regression analyses were conducted with stepwise adjustments for sociodemographic, socioeconomic and health-related covariates. RESULTS: Childhood and current socioeconomic disadvantage were associated with acute and chronic pain, particularly with chronic pain with high disability level. The strongest associations after adjustments for covariates remained between chronic pain with high disability level and low educational level (odds ratio (OR) 3.38, 95% confidence interval (CI) 2.18-5.24), manual occupation (OR 3.75, 95% CI 1.92-7.34) and experiencing frequent economic difficulties (OR 3.07, 95% CI 2.00-4.70). CONCLUSIONS: Pain is a common complaint that contributes to disability among young employees, particularly the most socioeconomically vulnerable. There is a socioeconomic gradient in both pain chronicity and the level of chronic pain-related disability. Life-course socioeconomic factors should be considered in pain-preventing strategies and in clinical practice.

Associations between low parental education, childhood adversities and sickness absence in midlife public sector employees.

AIMS: Parental education and childhood adversities are associated with long-term work disability but their contribution to sickness absence is largely unknown. We aimed to examine the associations between parental education, childhood adversities and self-certified and medically-certified sickness absence among midlife employees. METHODS: The Helsinki Health Study baseline survey data (2000-2002) of 40-to-60-year-old municipal employees were linked with sickness absence data from the employer's register. Self-certified (1-3 days) and medically-certified (>3 days) sickness absence spells were followed from 2003 until the end of 2008. The study included 5728 employees. The analyses were made by Poisson regression and the results are presented as rate ratios (RRs) and their 95% confidence intervals (CIs). RESULTS: Low maternal education was associated with self-certified sickness absence (RR 1.32, 95% CI 1.13-1.55) among women only whereas both low maternal (1.49, 1.26-1.77) and low paternal education (1.48, 1.32-1.67) were associated with medically-certified sickness absence. Adjustment for own occupational class mainly abolished these associations. Having experienced any childhood adversity was associated with self-certified (1.18, 1.12-1.25) and medically-certified (1.22, 1.15-1.30) sickness absence. In addition, childhood economic difficulties, childhood illness, parental divorce, parental mental illness, parental alcohol problems and bullying were each associated both with self-certified and with medically-certified sickness absence. The associations mainly remained after adjustments for occupational class, marital status, working condition, body mass index and health behaviours. CONCLUSIONS: Low parental education and childhood adversities contributed to midlife sickness absence. Promoting well-being of families with children might help sustain adult work ability and prevent sickness absence still in midlife.

Long-term sickness absence trajectories among ageing municipal employees - the contribution of social and health-related factors.

BACKGROUND: The ageing work force is heterogeneous, following distinct development in work ability. This study aims to identify trajectories of long-term sickness absence (SA) in later careers and to examine potentially modifiable factors associated with the development of SA. METHODS: Data comprised of municipal employees of the city of Helsinki aged 50-60 years during 2004-2018 (N = 4729, 80% women). The developmental trajectories of long-term (> 10 working days) SA were examined with Group-based trajectory modelling (GBTM) using SA records of the Social Insurance Institution of Finland during 2004-2018. All-cause and diagnosis-specific (mental disorder- and musculoskeletal disease-related) SA days were analysed. The association of social and health-related factors with trajectory membership was examined using multinomial logistic regression (odds ratios and 95% confidence intervals). RESULTS: A model with three trajectories was selected for both all-cause and diagnosis-specific SA. Regarding all-cause long-term SA trajectories, 42% had no long-term SA, 46% had low levels of SA, and 12% had a high rate of SA during follow-up. Lower occupational class, reporting smoking, overweight or obesity, moderate or low leisure-time physical activity, and sleep problems were associated with a higher likelihood of belonging to the trajectory with a high rate of SA in both all-cause and diagnosis-specific models. CONCLUSIONS: Most ageing employees have no or little long-term SA. Modifiable factors associated with trajectories with more SA could be targeted when designing and timing interventions in occupational healthcare.

Polygenic burden has broader impact on health, cognition, and socioeconomic outcomes than most rare and high-risk copy number variants.

Copy number variants (CNVs) are associated with syndromic and severe neurological and psychiatric disorders (SNPDs), such as intellectual disability, epilepsy, schizophrenia, and bipolar disorder. Although considered high-impact, CNVs are also observed in the general population. This presents a diagnostic challenge in evaluating their clinical significance. To estimate the phenotypic differences between CNV carriers and non-carriers regarding general health and well-being, we compared the impact of SNPD-associated CNVs on health, cognition, and socioeconomic phenotypes to the impact of three genome-wide polygenic risk score (PRS) in two Finnish cohorts (FINRISK, n = 23,053 and NFBC1966, n = 4895). The focus was on CNV carriers and PRS extremes who do not have an SNPD diagnosis. We identified high-risk CNVs (DECIPHER CNVs, risk gene deletions, or large [>1 Mb] CNVs) in 744 study participants (2.66%), 36 (4.8%) of whom had a diagnosed SNPD. In the remaining 708 unaffected carriers, we observed lower educational attainment (EA; OR = 0.77 [95% CI 0.66-0.89]) and lower household income (OR = 0.77 [0.66-0.89]). Income-associated CNVs also lowered household income (OR = 0.50 [0.38-0.66]), and CNVs with medical consequences lowered subjective health (OR = 0.48 [0.32-0.72]). The impact of PRSs was broader. At the lowest extreme of PRS for EA, we observed lower EA (OR = 0.31 [0.26-0.37]), lower-income (OR = 0.66 [0.57-0.77]), lower subjective health (OR = 0.72 [0.61-0.83]), and increased mortality (Cox's HR = 1.55 [1.21-1.98]). PRS for intelligence had a similar impact, whereas PRS for schizophrenia did not affect these traits. We conclude that the majority of working-age individuals carrying high-risk CNVs without SNPD diagnosis have a modest impact on morbidity and mortality, as well as the limited impact on income and educational attainment, compared to individuals at the extreme end of common genetic variation. Our findings highlight that the contribution of traditional high-risk variants such as CNVs should be analyzed in a broader genetic context, rather than evaluated in isolation.

Contributions of childhood adversities to chronic pain among mid-life employees.

Aims: Chronic pain is a notable burden on public health, with past and present factors contributing to it. This study aimed to examine the associations between childhood adversities and chronic pain. Methods: Data on seven childhood adversities, chronic pain and disabling pain were derived from questionnaire surveys conducted in 2000, 2001 and 2002 among 40- to 60-year-old employees (response rate of 67%) of the City of Helsinki, Finland. The study included 8140 employees (80% women). Logistic regression was used in the analyses, and the results are presented as odds ratios (OR) and their 95% confidence intervals (CI). Age, sex, the father's education, the participant's education, marital status, working conditions, sleep problems and common mental disorders were included as covariates. Results: In the age-adjusted models, childhood economic difficulties (OR=1.60, 95% CI 1.41-1.81), childhood illness (OR=1.74, 95% CI 1.45-2.08), parental divorce (OR=1.26, 95% CI 1.07-1.48), parental alcohol problems (OR=1.34, 95% CI 1.18-1.52) and bullying at school or among peers (OR=1.59, 95% CI 1.37-1.89) were associated with chronic pain. Working conditions, sleep problems and common mental disorders each slightly attenuated the associations between childhood adversities and chronic pain. Childhood economic difficulties among women (OR=1.72, 95% CI 1.40-2.10), childhood illness (OR=1.40, 95% CI 1.07-1.82) and bullying at school or by peers (OR=1.91 95% CI 1.48-2.46) were also associated with disabling pain. Conclusions: Childhood adversities were associated with chronic pain in mid-life, and the associations mainly remained after adjustments. Investing in the well-being of children might prevent pain and promote well-being in mid-life.

Joint association of socioeconomic circumstances and minor mental health problems with antidepressant medication.

BACKGROUND: Disadvantageous socioeconomic circumstances and minor mental health problems have both been associated with mental disorders, such as depression, but their joint contribution remains unknown. METHODS: The Helsinki Health Study baseline survey (2000-02) of 40- to 60-year-old employees was linked with antidepressant medication data from registers of the Social Insurance Institution of Finland. The analyses were made using logistic regression with first prescribed antidepressant medication purchase during a 10-year follow-up as the outcome. Minor mental health problems were measured by the emotional well-being scale of the RAND-36. Odds ratios were calculated for joint association of the lowest quartile of the emotional well-being scale of the RAND-36 and socioeconomic circumstances. Childhood (parental education and childhood economic difficulties), conventional (education, occupational class and income) and material (housing tenure and current economic difficulties) socioeconomic circumstances were examined. This study included 5450 participants. RESULTS: Minor mental health problems dominated the joint associations. Minor mental health problems were associated with antidepressant medication irrespective of socioeconomic circumstances whereas only low income, current economic difficulties and living in rented housing showed an association without minor mental health problems at baseline. Marital status, working conditions and BMI and health behaviours had only minimal contributions to the associations. CONCLUSIONS: Minor mental health problems were consistently and strongly associated with antidepressant medication and dominated the joint associations with socioeconomic circumstances. Paying attention to minor mental health problems might help prevent mental disorders such as depression.

Trajectories of working hours in later careers and their association with social and health-related factors: a follow-up study.

BACKGROUND: The aim was to identify working hours' trajectories in later work careers over a follow-up of 15-17 years and to examine their association with social factors and health. METHODS: A subsample from the Helsinki Health Study was extracted comprising employees of the City of Helsinki, Finland. Growth mixture modelling was used to identify different working hour trajectories. Age, gender, occupational class, marital status, health behaviour, physical and mental functioning and current pain were associated with trajectory membership. Relative risks (RRs) and their 95% confidence intervals (CIs) were estimated. RESULTS: A two-trajectory model was selected: 'Stable regular working hours' (90%) and 'Shorter and varying working hours' (10%). Women (RR 1.40, 95% CI 1.09-1.78), the oldest employees (RR 2.71, 95% CI 2.06-3.57), managers and professionals (RR 1.56, 95% CI 1.20-2.02), those reporting non-drinker (RR 1.66, 95% CI 1.32-2.10), those reporting sleeping more than 8 h per night (RR 1.74 95% CI 1.25-2.42) and those reporting poor mental functioning (RR 1.39 95% CI 1.15-1.68) had higher likelihood of belonging to the trajectory 'Shorter and varying working hours'. There were no differences between the trajectories in marital status, smoking, body mass index, current pain or physical functioning. However, routine non-manual workers (RR 0.74, 95% CI 0.55-0.98), and semi-professionals (RR 0.70, 95% CI 0.50-0.96) had lower likelihood of belonging to this trajectory. CONCLUSIONS: Trajectories of working hours in later work career differ by age, gender and occupational class but also by health behaviours and mental health functioning.

Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum.

There is a limited understanding about the impact of rare protein-truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitative traits and 10 diseases using whole-exome sequencing data from 100,296 individuals. Protein-truncating variants in genes intolerant to this class of mutations increased risk of autism, schizophrenia, bipolar disorder, intellectual disability, and ADHD. In individuals without these disorders, there was an association with shorter height, lower education, increased hospitalization, and reduced age at enrollment. Gene sets implicated from GWASs did not show a significant protein-truncating variants burden beyond what was captured by established Mendelian genes. In conclusion, we provide a thorough investigation of the impact of rare deleterious coding variants on complex traits, suggesting widespread pleiotropic risk.

Seeing an occupational health psychologist reduces sickness absence due to mental disorders: A quasi-experimental study.

Mental health problems are a major public health and work-life issue. We examined in a quasi-experimental design whether occupational health psychologist (OHP) appointment reduces subsequent sickness absence (SA) due to mental disorders among younger Finnish employees. The present study was conducted among 18-39-year-old employees of the City of Helsinki using register data from the City of Helsinki and the Social lnsurance Institution of Finland. We examined differences in SA days due to mental disorders (ICD-10, F-diagnosed sickness allowances) between those treated (at least one OHP appointment for work ability support) and the comparison group (no OHP appointment) during a one-year follow-up. The full sample (n = 2286, 84% women) consisted of employees with SA due to a diagnosed mental disorder during 2008-2017. To account for the systematic differences between the treatment and comparison groups, the included participants were matched according to age, sex, occupational class, education, previous SA, occupational health primary care visits and psychotropic medication. The weighted matched sample included 1351 participants. In the weighted matched sample, the mean of SA days due to mental disorders was 11.4 (95% CI, 6.4-16.5) for those treated (n = 238) and 20.2 (95% CI, 17.0-23.4) for the comparison group (p < 0.01) during the follow-up year. The corresponding figures in the full sample were (11.1, 6.7-15.4) days for those treated (n = 288) and (18.9, 16.7-21.1) days for the comparison group (p < 0.01). This quasi-experimental study suggests that seeing an OHP to support work ability reduces SA due to mental disorders.

The contribution of physical working conditions to sickness absence of varying length among employees with and without common mental disorders.

Aims: The aim was to examine whether the contribution of physical work exposures to the risk of sickness absence (SA) is different between those with and without common mental disorders (CMD). Methods: We used questionnaire data on four work exposures and CMD from 6159 participants of the Helsinki Health Study cohort with 12,458 observations from three surveys (2000-2002, 2007 and 2012). We formed combination exposures for the work exposures (hazardous exposures, physical workload, computer and shift work) with CMD. Associations with SA of different length were examined with negative binomial regression models. Results: We observed stronger associations for CMD with SA than for the individual work exposures. The strength of the associations for hazardous exposures and physical workload increased with length of SA, especially when the participant also had CMD. The strongest associations for the combined exposures were observed for SA ⩾15 days, the rate ratios being 2.63 (95% CI 2.27-3.05) among those with hazardous exposure and CMD, and 3.37 (95% CI 2.93-3.88) among those with heavy physical workload and CMD. Conclusions: Employees with hazardous exposures or physical workload combined with CMD were at the highest risk of SA compared with those without these exposures or with only one exposure.

Predictors of working days lost due to sickness absence and disability pension.

OBJECTIVE: To identify social and health-related predictors of the number of days lost due to sickness absence (SA) and disability pension (DP) among initially 55-year-old public-sector workers. METHODS: The data from the Finnish Helsinki Health Study included participants aged 55 years at the baseline (in 2000-2002, N = 1630, 81% women), and were enriched with register-based information on SA and DP. The cumulative number of calendar days lost due to SA ≥ 1 day or DP between ages 55 and 65 was calculated. Negative binomial regression model was used to identify the predictors of days lost. RESULTS: The average calendar days lost was 316 days (about 220 working days) during a 10-year follow-up, and 44% were due to SA and 56% due to DP. Smoking [incidence rate ratio (IRR) = 1.19, 95% CI 1.01-1.40 for past and IRR = 1.30, CI 1.07-1.58 for current], binge drinking (IRR = 1.22, CI 1.02-1.46), lifting or pulling/pushing heavy loads (IRR = 1.35, CI 1.10-1.65), awkward working positions (IRR = 1.24, CI 1.01-1.53), long-standing illness limiting work or daily activities (IRR = 2.32, CI 1.93-2.79), common mental disorder (IRR = 1.52, CI 1.30-1.79), and multisite pain (IRR = 1.50, CI 1.23-1.84) increased the number of days lost, while high level of education (IRR = 0.66, CI 0.52-0.82) and moderate level of leisure-time physical activity (IRR = 0.80, CI 0.67-0.94) reduced the number of days lost. CONCLUSIONS: Modifiable lifestyle risk factors, workload factors, common mental disorder, and multisite pain substantially increase the number of days lost. However, the findings of this study could be generalized to female workers in the public sector. Future research should also consider shorter SA spells in estimating working years lost and working life expectancy.

Frequent short sickness absence, occupational health service utilisation and long-term sickness absence due to mental disorders among young employees.

OBJECTIVES: We examined whether frequent short-term sickness absence (FSTSA) and primary care use in occupational health service (OHS) were associated with medically-certified long-term sickness absence (LTSA) due to mental disorders among young employees. METHODS: We used record-linkage data covering the young employees (< 35 years) of the City of Helsinki, Finland (n = 8,282) from 2010 to 2014. The outcome was LTSA due to mental disorders. Cox regression models were fitted. RESULTS: FSTSAs were associated with subsequent LTSA. Also OHS use predicted LTSA due to mental disorders; however, this association was not found for those with prior FSTSA. CONCLUSIONS: Both FSTSA and primary care use indicate subsequent LTSA independently, and together these indicators identify a larger proportion of individuals at risk of LTSA due to mental disorders.

Long working hours and change in body weight: analysis of individual-participant data from 19 cohort studies.

OBJECTIVE: To examine the relation between long working hours and change in body mass index (BMI). METHODS: We performed random effects meta-analyses using individual-participant data from 19 cohort studies from Europe, US and Australia (n = 122,078), with a mean of 4.4-year follow-up. Working hours were measured at baseline and categorised as part time (<35 h/week), standard weekly hours (35-40 h, reference), 41-48 h, 49-54 h and ≥55 h/week (long working hours). There were four outcomes at follow-up: (1) overweight/obesity (BMI ≥ 25 kg/m2) or (2) overweight (BMI 25-29.9 kg/m2) among participants without overweight/obesity at baseline; (3) obesity (BMI ≥ 30 kg/m2) among participants with overweight at baseline, and (4) weight loss among participants with obesity at baseline. RESULTS: Of the 61,143 participants without overweight/obesity at baseline, 20.2% had overweight/obesity at follow-up. Compared with standard weekly working hours, the age-, sex- and socioeconomic status-adjusted relative risk (RR) of overweight/obesity was 0.95 (95% CI 0.90-1.00) for part-time work, 1.07 (1.02-1.12) for 41-48 weekly working hours, 1.09 (1.03-1.16) for 49-54 h and 1.17 (1.08-1.27) for long working hours (P for trend <0.0001). The findings were similar after multivariable adjustment and in subgroup analyses. Long working hours were associated with an excess risk of shift from normal weight to overweight rather than from overweight to obesity. Long working hours were not associated with weight loss among participants with obesity. CONCLUSIONS: This analysis of large individual-participant data suggests a small excess risk of overweight among the healthy-weight people who work long hours.

Changes in fruit, vegetable and fish consumption after statutory retirement: a prospective cohort study.

Retirement is a major life transition affecting health and health behaviour, but evidence on how this transition contributes to changes in healthy food habits is scarce. We examined whether the consumption of fruit and vegetables as well as fish changes after transition into statutory retirement. The data were derived from the prospective Helsinki Health Study. At phase 1 in 2000-2002, all participants were 40- to 60-year-old employees of the City of Helsinki, Finland (n 8960, response rate 67 %). Follow-up surveys were conducted in 2007, 2012 and 2017 (response rates 79-83 %). Using the four phases, we formed three nested cohorts in which the participants either continued working or moved to statutory retirement. The final analytical sample consisted of 6887 participants (14 357 observations). Frequency of fruit, vegetable and fish consumption was calculated from a twenty-two-item FFQ. Analyses of repeated measures of food consumption before and after retirement transition were conducted with a negative binomial mixed model, adjusting for age, marital status, limiting long-standing illness and household income. During the follow-up, altogether 3526 participants retired. Transition to retirement was associated with a decrease in vegetable consumption among women and, contrarily, with an increase in fruit consumption among men (P < 0·05 for interaction between time and employment status). Fish consumption did not differ by the change in employment status. Statutory retirement can have mixed effects on healthy food habits, and these can differ between food groups and sex. Healthy food habits should be promoted among employees transitioning to retirement.

Who maintains good health functioning? The contribution of social, work-related and behavioural factors to mental and physical health functioning trajectories in ageing employees.

OBJECTIVES: The determinants of poor functioning and subsequent early exit from work are well established but very little is known about the positive determinants of maintaining good functioning among the ageing workforce. We investigated modifiable determinants of maintaining good mental and physical health functioning. METHODS: We used prospective survey data collected across four waves among the midlife employees of the City of Helsinki, Finland, 2000-2017 (n=3342). Health functioning was repeatedly measured using the Short Form 36 (SF-36) inventory. Trajectories of mental and physical health functioning were separately examined using group-based trajectory analysis. Multinomial logistic regression models were fitted to examine determinants of each trajectory. RESULTS: Four trajectory solutions for the developmental patterns in health functioning during the follow-up period were selected, with a slightly different shape of the first trajectory for mental and physical functioning: (1) continuously low (mental), low and decreasing (physical), (2) increasing, (3) decreasing and (4) continuously high functioning. After adjustments, the employees in the continuously high mental health functioning group were more likely to have optimal job demands, high job control, no sleep problems and no binge drinking behaviour. Employees in the continuously high physical functioning group had more likely low levels of physically strenuous work and hazardous working environment and no sleep problems and normal weight. CONCLUSION: High job control, good sleep and avoiding binge drinking may help maintain good mental health functioning. Low levels of physical or environmental work exposures, good sleep and recommended healthy weight may support maintenance of good physical health functioning among ageing employees.