Job strain as a risk factor for clinical depression: systematic review and meta-analysis with additional individual participant data.

BACKGROUND: Adverse 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. METHOD: We 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published cohort studies from a systematic literature search in PubMed and PsycNET and obtained 14 cohort studies with unpublished individual-level data from the Individual-Participant-Data Meta-analysis in Working Populations (IPD-Work) Consortium.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. RESULTS: We 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 From unpublished datasets we included 120 221 individuals and 982 first episodes of hospital-treated clinical depression.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risk of clinical depression in both published [relative risk (RR) = 1.77, 95% confidence interval (CI) 1.47-2.13] and unpublished datasets (RR = 1.27, 95% CI 1.04-1.55).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). CONCLUSIONS: Job strain may precipitate clinical depression among employees. Future intervention studies should test whether job strain is a modifiable risk factor for depression.

Diabetes and risk of occupational injury: a cohort study.

AIMS: To investigate if diabetes is associated with a higher risk of occupational (workplace or commuting) injury. METHODS: Medication data from the Finnish Prescription Register were used to identify diabetes cases in 2004 in a large employee cohort (the Finnish Public Sector study). These data were linked to injury records obtained from the Federation of Accident Insurance Institutions. A total of 1020 diabetes cases (median age 52 years, range 20 to 65 years; 66% women) and their 5234 age- and sex-matched controls were followed up until 2011. Sex-stratified Cox proportional hazards models, adjusting for age, occupational status, obesity and health behaviours, were applied. Because of the small number of men in the cohort, injury types and locations were only examined among women. RESULTS: During the median follow-up of 6.7 years, 25% of the participants with diabetes (n=252) and 20% of those without (n=1051) experienced an occupational injury. The association between diabetes and injury was stronger in women than men (P=0.048). Diabetes was associated with a higher risk of workplace (hazard ratio 1.37, 95% CI 1.11 to 1.69) and commuting (hazard ratio 1.36, 95% CI 1.03 to 1.79) injury in women. With regard to different injury types and locations, diabetes was associated with bone fractures, dislocations, sprains and strains, and injuries to upper and lower extremities. In men, there was an association between insulin-treated diabetes and commuting injury (hazard ratio 3.14, 95% CI 1.52 to 6.49). CONCLUSIONS: Diabetes was associated with workplace and commuting injuries in women. Men with insulin-treated diabetes had a higher risk of commuting injuries.

Antidepressant use and work-related injuries.

BACKGROUND: Adverse effects of antidepressants are most common at the beginning of the treatment, but possible also later. We examined the association between antidepressant use and work-related injuries taking into account the duration of antidepressant use. METHOD: Antidepressant use and work-related injuries between 2000 and 2011 were measured among 66 238 employees (mean age 43.8 years, 80% female) using linkage to national records (the Finnish Public Sector study). We analysed data using time-dependent modelling with individuals as their own controls (self-controlled case-series design). RESULTS: In 2238 individuals who had used antidepressants and had a work-related injury during a mean follow-up of 7.8 years, no increase in the risk of injury was observed in the beginning of antidepressant treatment. However, an increased injury risk was seen after 3 months of treatment (rate ratio, compared with no recent antidepressant use, 1.27, 95% confidence interval 1.10-1.48). This was also the case among those who had used only selective serotonin reuptake inhibitors (n = 714; rate ratio 1.41, 95% confidence interval 1.08-1.83). CONCLUSIONS: Antidepressant use was not associated with an increased risk of work-related injury at the beginning of treatment. Post-hoc analyses of antidepressant trials are needed to determine whether long-term use of antidepressants increases the risk of work-related injury.

Psychosocial factors associated with work disability in men and women with diabetes: a pooled analysis of three occupational cohort studies.

AIMS: To examine the extent to which adverse psychosocial factors, such as living alone, psychological distress, job strain and low support from supervisor, increase the risk of work disability (sickness absence and disability pension) among employees with diabetes. METHODS: In this pooled analysis of individual-participant data from three occupational cohort studies (the Finnish Public Sector Study, the British Whitehall II study, and the French GAZEL study), 1088 women and 949 men with diabetes were followed up to determine the duration (number of days) and frequency (number of spells) of work disability. The mean follow-up periods were 3.2 years in the GAZEL study, 4.6 years in the Whitehall II study and 4.7 years in the Finnish Public Sector Study. Psychosocial factors and potential confounding factors were assessed at baseline using standard questionnaires. Study-specific estimates were pooled using fixed-effects meta-analysis. RESULTS: In analysis adjusted for sociodemographic factors, health behaviours and comorbidities, participants with psychological distress had longer (rate ratio 1.66; 95% CI 1.31-2.09) and more frequent absences (rate ratio 1.33; 95% CI 1.19-1.49) compared with those with no psychological distress. Job strain was associated with slightly increased absence frequency (rate ratio 1.19 95% CI 1.05-1.35), but not with absence duration. Living alone and low supervisor support were not associated with absence duration or frequency. We observed no sex differences in these associations. CONCLUSIONS: Psychological distress was associated with increased duration and frequency of work disability among employees with diabetes. Job strain was associated with increased absence frequency but not with absence duration.

Job strain and risk of obesity: systematic review and meta-analysis of cohort studies.

Job strain, the most widely used indicator of work stress, is a risk factor for obesity-related disorders such as cardiovascular disease and type 2 diabetes. However, the extent to which job strain is related to the development of obesity itself has not been systematically evaluated. We carried out a systematic review (PubMed and Embase until May 2014) and meta-analysis of cohort studies to address this issue. Eight studies that fulfilled inclusion criteria showed no overall association between job strain and the risk of weight gain (pooled odds ratio for job strain compared with no job strain 1.04, 95% confidence interval (CI) 0.99-1.09, NTotal=18 240) or becoming obese (1.00, 95% CI 0.89-1.13, NTotal=42 222). In addition, a reduction in job strain over time was not associated with lower obesity risk (1.13, 95% CI 0.90-1.41, NTotal=6507). These longitudinal findings do not support the hypothesis that job strain is an important risk factor for obesity or a promising target for obesity prevention.

Interleukin-6 as a predictor of symptom resolution in psychological distress: a cohort study.

BACKGROUND: Elevated levels of interleukin-6 (IL-6) have been associated with the development of common mental disorders, such as depression, but its role in symptom resolution is unclear. METHOD: We examined the association between IL-6 and symptom resolution in a non-clinical sample of participants with psychological distress. RESULTS: Relative to high IL-6 levels, low levels at baseline were associated with symptom resolution at follow-up [age- and sex-adjusted risk ratio (RR) = 1.15, 95% confidence interval (CI) 1.06-1.25]. Further adjustment for covariates had little effect on the association. Symptomatic participants with repeated low IL-6 were more likely to be symptom-free at follow-up compared with those with repeated high IL-6 (RR = 1.21, 95% CI 1.03-1.41). Among the symptomatic participants with elevated IL-6 at baseline, IL-6 decreased along with symptom resolution. CONCLUSIONS: IL-6 is potentially related to the mechanisms underlying recovery from symptoms of mental ill health. Further studies are needed to examine these mechanisms and to confirm the findings in relation to clinical depression.

Lifestyle-related risk factors and trajectories of work disability over 5 years in employees with diabetes: findings from two prospective cohort studies.

AIMS: To examine work disability trajectories among employees with and without diabetes and identify lifestyle-related factors associated with these trajectories. METHODS: We assessed work disability using records of sickness absence and disability pension among participants with diabetes and age- sex-, socio-economic status- and marital status-matched controls in the Finnish Public Sector Study (1102 cases; 2204 controls) and the French GAZEL study (500 cases; 1000 controls), followed up for 5 years. Obesity, physical activity, smoking and alcohol consumption were assessed at baseline and the data analysed using group-based trajectory modelling. RESULTS: Five trajectories described work disability: 'no/very low disability' (41.1% among cases and 48.0% among controls); 'low-steady' (35.4 and 34.7%, respectively); 'high-steady' (13.6 and 12.1%, respectively); and two 'high-increasing' trajectories (10.0 and 5.2%, respectively). Diabetes was associated with a 'high-increasing' trajectory only (odds ratio 1.90, 95% CI 1.47-2.46). Obesity and low physical activity were similarly associated with high work disability in people with and without diabetes. Smoking was associated with 'high-increasing' trajectory in employees with diabetes (odds ratio 1.88, 95% CI 1.21-2.93) but not in those without diabetes (odds ratio 1.32, 95% CI 0.87-2.00). Diabetes was associated with having multiple ( ≥ 2) risk factors (21.1 vs. 11.4%) but the association between multiple risk factors and the 'high-increasing' trajectory was similar in both groups. CONCLUSIONS: The majority of employees with diabetes have low disability rates, although 10% are on a high and increasing disability trajectory. Lifestyle-related risk factors have similar associations with disability among employees with and without diabetes, except smoking which was only associated with poorer prognosis in diabetes.

Excess mortality among the elderly in European countries, December 2014 to February 2015.

Since December 2014 and up to February 2015, the weekly number of excess deaths from all-causes among individuals ≥ 65 years of age in 14 European countries have been significantly higher than in the four previous winter seasons. The rise in unspecified excess mortality coincides with increased proportion of influenza detection in the European influenza surveillance schemes with a main predominance of influenza A (H3N2) viruses seen throughout Europe in the current season, though cold snaps and other respiratory infections may also have had an effect.

Job strain and the risk of severe asthma exacerbations: a meta-analysis of individual-participant data from 100 000 European men and women.

BACKGROUND: Many patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. METHODS: We analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. RESULTS: During a median follow-up of 10 years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). CONCLUSIONS: Our findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.

Estimating the burden of A(H1N1)pdm09 influenza in Finland during two seasons.

In Finland, the pandemic influenza virus A(H1N1)pdm09 was the dominant influenza strain during the pandemic season in 2009/2010 and presented alongside other influenza types during the 2010/2011 season. The true number of infected individuals is unknown, as surveillance missed a large portion of mild infections. We applied Bayesian evidence synthesis, combining available data from the national infectious disease registry with an ascertainment model and prior information on A(H1N1)pdm09 influenza and the surveillance system, to estimate the total incidence and hospitalization rate of A(H1N1)pdm09 infection. The estimated numbers of A(H1N1)pdm09 infections in Finland were 211 000 (4% of the population) in the 2009/2010 pandemic season and 53 000 (1% of the population) during the 2010/2011 season. Altogether, 1·1% of infected individuals were hospitalized. Only 1 infection per 25 was ascertained.

A Scandinavian case of skin fragility, alopecia and cardiomyopathy caused by DSP mutations.

Congenital skin fragility is a heterogeneous disorder with epidermolysis bullosa and various skin infections as the leading causes. However, even rare diseases must be considered in the differential diagnosis of neonatal skin blistering, including some genetic syndromes with extracutaneous involvement. One such syndrome is ectodermal dysplasia due to deficiency of desmoplakin, a desmosomal protein essential for cellular cohesion in both epithelia and cardiac tissues. Desmoplakin is encoded by the DSP gene, which is localized on chromosome 6p24. Both dominant and recessive mutations in this gene have been reported to cause skin fragility and keratinization defects. We report a child born with a fragile epidermis, alopecia, thick nails, and focal hyperkeratoses on the digits and knees. She was found to have a deficiency of desmoplakin caused by compound heterozygous DSP mutations. She has gradually developed signs of a left ventricular cardiomyopathy.

Pooling European all-cause mortality: methodology and findings for the seasons 2008/2009 to 2010/2011.

Several European countries have timely all-cause mortality monitoring. However, small changes in mortality may not give rise to signals at the national level. Pooling data across countries may overcome this, particularly if changes in mortality occur simultaneously. Additionally, pooling may increase the power of monitoring populations with small numbers of expected deaths, e.g. younger age groups or fertile women. Finally, pooled analyses may reveal patterns of diseases across Europe. We describe a pooled analysis of all-cause mortality across 16 European countries. Two approaches were explored. In the 'summarized' approach, data across countries were summarized and analysed as one overall country. In the 'stratified' approach, heterogeneities between countries were taken into account. Pooling using the 'stratified' approach was the most appropriate as it reflects variations in mortality. Excess mortality was observed in all winter seasons albeit slightly higher in 2008/09 than 2009/10 and 2010/11. In the 2008/09 season, excess mortality was mainly in elderly adults. In 2009/10, when pandemic influenza A(H1N1) dominated, excess mortality was mainly in children. The 2010/11 season reflected a similar pattern, although increased mortality in children came later. These patterns were less clear in analyses based on data from individual countries. We have demonstrated that with stratified pooling we can combine local mortality monitoring systems and enhance monitoring of mortality across Europe.

Seasonal patterns of sickness absence due to diagnosed mental disorders: a nationwide 12-year register linkage study.

AIMS: Although seasonality has been documented for mental disorders, it is unknown whether similar patterns can be observed in employee sickness absence from work due to a wide range of mental disorders with different severity level, and to what extent the rate of change in light exposure plays a role. To address these limitations, we used daily based sickness absence records to examine seasonal patterns in employee sickness absence due to mental disorders. METHODS: We used nationwide diagnosis-specific psychiatric sickness absence claims data from 2006 to 2017 for adult individuals aged 16-67 (n = 636,543 sickness absence episodes) in Finland, a high-latitude country with a profound variation in daylength. The smoothed time-series of the ratio of observed and expected (O/E) daily counts of episodes were estimated, adjusted for variation in all-cause sickness absence rates during the year. RESULTS: Unipolar depressive disorders peaked in October-November and dipped in July, with similar associations in all forms of depression. Also, anxiety and non-organic sleep disorders peaked in October-November. Anxiety disorders dipped in January-February and in July-August, while non-organic sleep disorders dipped in April-August. Manic episodes reached a peak from March to July and dipped in September-November and in January-February. Seasonality was not dependent on the severity of the depressive disorder. CONCLUSIONS: These results suggest a seasonal variation in sickness absence due to common mental disorders and bipolar disorder, with high peaks in depressive, anxiety and sleep disorders towards the end of the year and a peak in manic episodes starting in spring. Rapid changes in light exposure may contribute to sickness absence due to bipolar disorder. The findings can help clinicians and workplaces prepare for seasonal variations in healthcare needs.

Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies.

BACKGROUND: Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. OBJECTIVES: To examine the association between job strain and body mass index (BMI) in a large adult population. METHODS: We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). RESULTS: A total of 86 429 participants were of normal weight (BMI 18.5-24.9 kg m(-2) ), 2149 were underweight (BMI < 18.5 kg m(-2) ), 56 572 overweight (BMI 25.0-29.9 kg m(-2) ) and 13 523 class I (BMI 30-34.9 kg m(-2) ) and 3073 classes II/III (BMI ≥ 35 kg m(-2) ) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.00-1.25], obese class I (odds ratio 1.07, 95% CI 1.02-1.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.01-1.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. CONCLUSIONS: In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a 'U'-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level.

Excess mortality among the elderly in 12 European countries, February and March 2012.

In February and March 2012, excess deaths among the elderly have been observed in 12 European countries that carry out weekly monitoring of all-cause mortality. These preliminary data indicate that the impact of influenza in Europe differs from the recent pandemic and post-pandemic seasons. The current excess mortality among the elderly may be related to the return of influenza A(H3N2) virus, potentially with added effects of a cold snap.

Long working hours and symptoms of anxiety and depression: a 5-year follow-up of the Whitehall II study.

BACKGROUND: Although long working hours are common in working populations, little is known about the effect of long working hours on mental health. METHOD: We examined the association between long working hours and the onset of depressive and anxiety symptoms in middle-aged employees. Participants were 2960 full-time employees aged 44 to 66 years (2248 men, 712 women) from the prospective Whitehall II cohort study of British civil servants. Working hours, anxiety and depressive symptoms, and covariates were measured at baseline (1997-1999) followed by two subsequent measurements of depressive and anxiety symptoms (2001 and 2002-2004). RESULTS: In a prospective analysis of participants with no depressive (n=2549) or anxiety symptoms (n=2618) at baseline, Cox proportional hazard analysis adjusted for baseline covariates showed a 1.66-fold [95% confidence interval (CI) 1.06-2.61] risk of depressive symptoms and a 1.74-fold (95% CI 1.15-2.61) risk of anxiety symptoms among employees working more than 55 h/week compared with employees working 35-40 h/week. Sex-stratified analysis showed an excess risk of depression and anxiety associated with long working hours among women [hazard ratios (HRs) 2.67 (95% CI 1.07-6.68) and 2.84 (95% CI 1.27-6.34) respectively] but not men [1.30 (0.77-2.19) and 1.43 (0.89-2.30)]. CONCLUSIONS: Working long hours is a risk factor for the development of depressive and anxiety symptoms in women.

Immortalized keratinocytes derived from patients with epidermolytic ichthyosis reproduce the disease phenotype: a useful in vitro model for testing new treatments.

BACKGROUND: Epidermolytic ichthyosis (EI) is a skin fragility disorder caused by mutations in genes encoding suprabasal keratins 1 and 10. While the aetiology of EI is known, model systems are needed for pathophysiological studies and development of novel therapies. OBJECTIVES: To generate immortalized keratinocyte lines from patients with EI for studies of EI cell pathology and the effects of chemical chaperones as putative therapies. METHODS: We derived keratinocytes from three patients with EI and one healthy control and established immortalized keratinocytes using human papillomavirus 16-E6/E7. Growth and differentiation characteristics, ability to regenerate organotypic epidermis, keratin expression, formation of cytoskeletal aggregates, and responses to heat shock and chemical chaperones were assessed. RESULTS: The cell lines EH11 (K1_p.Val176_Lys197del), EH21 (K10_p.156Arg>Gly), EH31 (K10_p.Leu161_Asp162del) and NKc21 (wild-type) currently exceed 160 population doublings and differentiate when exposed to calcium. At resting state, keratin aggregates were detected in 9% of calcium-differentiated EH31 cells, but not in any other cell line. Heat stress further increased this proportion to 30% and also induced aggregates in 3% of EH11 cultures. Treatment with trimethylamine N-oxide and 4-phenylbutyrate (4-PBA) reduced the fraction of aggregate-containing cells and affected the mRNA expression of keratins 1 and 10 while 4-PBA also modified heat shock protein 70 (HSP70) expression. Furthermore, in situ proximity ligation assay suggested a colocalization between HSP70 and keratins 1 and 10. Reconstituted epidermis from EI cells cornified but EH21 and EH31 cells produced suprabasal cytolysis, closely resembling the in vivo phenotype. CONCLUSIONS: These immortalized cell lines represent a useful model for studying EI biology and novel therapies.

An extensive gastroenteritis outbreak after drinking-water contamination by sewage effluent, Finland.

An inappropriate cross-connection between sewage- and drinking-water pipelines contaminated tap water in a Finnish town, resulting in an extensive waterborne gastroenteritis outbreak in this developed country. According to a database and a line-list, altogether 1222 subjects sought medical care as a result of this exposure. Seven pathogens were found in patient samples of those who sought treatment. To establish the true disease burden from this exposure, we undertook a population-based questionnaire investigation with a control population, infrequently used to study waterborne outbreaks. The study covered three areas, contaminated and uncontaminated parts of the town and a control town. An estimated 8453 residents fell ill during the outbreak, the excess number of illnesses being 6501. Attack rates were 53% [95% confidence interval (CI) 49.5-56.4] in the contaminated area, 15.6% (95% CI 13.1-18.5) in the uncontaminated area and 6.5% (95% CI 4.8-8.8) in the control population. Using a control population allowed us to differentiate baseline morbidity from the observed morbidity caused by the water contamination, thus enabling a more accurate estimate of the disease burden of this outbreak.

Preoperative levosimendan infusion in combined aortic valve and coronary bypass surgery.

BACKGROUND: Cardiopulmonary bypass may have detrimental effects on intestinal function and decrease the concentrations of the active, long-acting metabolites of levosimendan, an inodilator used to improve cardiac function. The aim of this study was to evaluate the haemodynamic effects of preoperative levosimendan in patients undergoing high-risk cardiac surgery. METHODS: Twenty-four patients were randomized to receive levosimendan (12 µg bolus followed by an infusion of 0.2 µg kg(-1) min(-1)) or a placebo 24 h before surgery. The inclusion criteria were left ventricular ejection fraction (LVEF) <50% or LV hypertrophy indicated by a wall thickness of >12 mm. Haemodynamics were recorded every hour for 24 h (pulmonary artery catheter) and daily until postoperative day 4 (whole-body impedance cardiography). Doppler echocardiography with tissue Doppler imaging was used to assess systolic and diastolic cardiac function. RESULTS: The cardiac index (CI) and stroke volume index (SI) were higher in the levosimendan group (LG) for the 4 day postoperative period (P<0.05); on the fourth postoperative day, the CI was 3.0 litre m(-2) min(-1) in the LG compared with 2.4 litre m(-2) min(-1) in the control group (CG) and the SI was 30 vs 25 ml m(-2), respectively. The LVEF measured at baseline and on the fourth postoperative morning decreased in the CG, but was maintained in the LG. CONCLUSIONS: Levosimendan improved haemodynamics compared with a placebo in patients undergoing high-risk cardiac surgery. The concentrations of levosimendan's metabolites were higher compared with earlier studies using perioperative dosing.