Identifying return to work trajectories among employees on sick leave due to mental health problems using latent class transition analysis

Objectives To develop effective return to work (RTW) interventions for employees on sick leave due to mental health problems (MHPs), a better understanding of individual variation in the RTW process is needed. We investigated which RTW trajectories can be identified among employees with MHPs in terms of RTW duration and relapse occurrence during the RTW process. Additionally, we examined how different RTW trajectories can be described in terms of personal and work characteristics. Methods Longitudinal sickness absence registry data were collected retrospectively from the largest Dutch occupational health service. Quantitative RTW information as well as personal and work characteristics were extracted. In total, 9517 employees with a sickness absence due to MHPs were included in the analyses (62 938 data points; RTW durations from 29 to 730 days). Results A latent class transition analysis revealed five distinct RTW trajectories, namely (1) fast RTW with little chance of relapse, (2) slow RTW with little chance of relapse, (3) fast RTW with considerable chance of relapse, (4) slow RTW with considerable chance of relapse and (5) very fast RTW with very small chance of relapse. Differences between employees in the slower and faster trajectories were observed regarding gender, age, type of MHP, organisation sector and organisation size but not regarding part-time work. Conclusions RTW trajectories among employees with MHPs showed large individual variability and differed on personal and work characteristics. Knowledge on different RTW trajectories and their characteristics contributes to the development of personalised RTW treatments, tailored to specific individuals and organis

MicroRNA-214 inhibits angiogenesis by targeting Quaking and reducing angiogenic growth factor release

Signal transduction in aging related disease

The circadian clock remains intact, but with dampened hormonal output in heart failure.

BACKGROUND: Circadian (24-h) rhythms are important regulators in physiology and disease, but systemic disease may disrupt circadian rhythmicity. Heart failure (HF) is a systemic disease affecting hormonal regulation. We investigate whether HF affects the rhythmic expression of melatonin and cortisol, main endocrine products of the central clock, and cardiac-specific troponin in patients. We corroborate the functionality of the peripheral clock directly in the organs of translational models, inaccessible in human participants. METHODS: We included 46 HF patients (71.7% male, median age of 60 years, NYHA class II (32.6%) or III (67.4%), ischemic cardiomyopathy (43.5%), comorbidities: diabetes 21.7%, atrial fibrillation 30.4%), and 24 matched controls. Blood was collected at seven time-points during a 24-h period (totalling 320 HF and 167 control samples) for melatonin, cortisol, and cardiac troponin T (cTnT) measurements after which circadian rhythms were assessed through cosinor analyses, both on the individual and the group level. Next, we analysed peripheral circadian clock functionality using cosinor analysis in male animal HF models: nocturnal mice and diurnal zebrafish, based on expression of core clock genes in heart, kidneys, and liver, every 4 h during a 24-h period in a light/darkness synchronised environment. FINDINGS: Melatonin and cortisol concentrations followed a physiological 24-h pattern in both patients and controls. For melatonin, acrophase occurred during the night for both groups, with significantly decreased amplitude (median 5.2 vs 8.8, P = 0.0001) and circadian variation ([maximum]/[minimum]) in heart failure patients. For cortisol, mesor showed a significant increase for HF patients (mean 331.9 vs 275.1, P = 0.017) with a difference of 56.8 (95% CI 10.3-103.3) again resulting in a relatively lower variation: median 3.9 vs 6.3 (P = 0.0058). A nocturnal blood pressure dip was absent in 77.8% of HF patients. Clock gene expression profiles (Bmal, Clock, Per, Cry) were similar and with expected phase relations in animal HF models and controls, demonstrating preserved peripheral clock functionality in HF. Furthermore, oscillations in diurnal zebrafish were expectedly in opposite phases to those of nocturnal mice. Concordantly, cTnT concentrations in HF patients revealed significant circadian oscillations. INTERPRETATION: Central clock output is dampened in HF patients while the molecular peripheral clock, as confirmed in animal models, remains intact. This emphasises the importance of taking timing into account in research and therapy for HF, setting the stage for another dimension of diagnostic, prognostic and therapeutic approaches. FUNDING: Hartstichting