Factors associated with first return to work and sick leave durations in workers with common mental disorders

Background: Associations are examined between socio-demographic, medical, work-related and organizational factors and the moment of first return to work (RTW) (within or after 6 weeks of sick leave) and total sick leave duration in sick leave spells due to common mental disorders. Methods: Data are derived from a Dutch database, build to provide reference data for sick leave duration for various medical conditions. The cases in this study were entered in 2004 and 2005 by specially trained occupational health physicians, based on the physician's assessment of medical and other factors. Odds ratios for first RTW and sick leave durations are calculated in logistic regression models. Results: Burnout, depression and anxiety disorder are associated with longer sick leave duration. Similar, but weaker associations were found for female sex, being a teacher, small company size and moderate or high psychosocial hazard. Distress is associated with shorter sick leave duration. Medical factors, psychosocial hazard and company size are also and analogously associated with first RTW. Part-time work is associated with delayed first RTW. The strength of the associations varies for various factors and for different sick leave durations. Conclusion: The medical diagnosis has a strong relation with the moment of first RTW and the duration of sick leave spells in mental disorders, but the influence of demographic and work-related factors should not be neglected

A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol

Corifollitropin alfa, a fusion protein lacking LH activity, has a longer elimination half-life and extended time to peak levels than recombinant FSH (rFSH). A single injection of corifollitropin alfa may replace seven daily gonadotrophin injections during the first week of ovarian stimulation. In this large, double-blind, randomized, non-inferiority trial the ongoing pregnancy rates were assessed after one injection of 150 mu g corifollitropin alfa during the first week of stimulation and compared with daily injections of 200 IU rFSH using a standard GnRH antagonist protocol. The study population comprised 1506 treated patients with mean age of 31.5 years and body weight of 68.6 kg. Ongoing pregnancy rates of 38.9% for the corifollitropin alfa group and 38.1% for rFSH were achieved, with an estimated non-significant difference of 0.9% [95% confidence interval (CI): -3.9; 5.7] in favor of corifollitropin alfa. Stratified analyses of pregnancy rates confirmed robustness of this primary outcome by showing similar results regardless of IVF or ICSI, or number of embryos transferred. A slightly higher follicular response with corifollitropin alfa resulted in a higher number of cumulus-oocyte-complexes compared with rFSH [estimated difference 1.2 (95% CI: 0.5; 1.9)], whereas median duration of stimulation was equal (9 days) and incidence of (moderate/severe) ovarian hyperstimulation syndrome was the same (4.1 and 2.7%, respectively P = 0.15). Corifollitropin alfa is a novel and effective treatment option for potential normal responder patients undergoing ovarian stimulation with GnRH antagonist co-treatment for IVF resulting in a high ongoing pregnancy rate, equal to that achieved with daily rFSH. The trial was registered under ClinicalTrials.gov identifier NTC00696800

Activation of interferon regulatory factor-3 via toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA

U1-snRNA is an integral part of the U1 ribonucleoprotein pivotal for pre-mRNA splicing. Toll-like receptor (TLR) signaling has recently been associated with immunoregulatory capacities of U1-snRNA. Using lung A549 epithelial/carcinoma cells, we report for the first time on interferon regulatory factor (IRF)-3 activation initiated by endosomally delivered U1-snRNA. This was associated with expression of the IRF3-inducible genes interferon-β (IFN-β), CXCL10/IP-10 and indoleamine 2,3-dioxygenase. Mutational analysis of the U1-snRNA-activated IFN-β promoter confirmed the crucial role of the PRDIII element, previously proven pivotal for promoter activation by IRF3. Notably, expression of these parameters was suppressed by bafilomycin A1, an inhibitor of endosomal acidification, implicating endosomal TLR activation. Since resiquimod, an agonist of TLR7/8, failed to stimulate A549 cells, data suggest TLR3 to be of prime relevance for cellular activation. To assess the overall regulatory potential of U1-snRNA-activated epithelial cells on cytokine production, co-cultivation with peripheral blood mononuclear cells (PBMC) was performed. Interestingly, A549 cells activated by U1-snRNA reinforced phytohemagglutinin-induced interleukin-10 release by PBMC but suppressed that of tumor necrosis factor-α, indicating an anti-inflammatory potential of U1-snRNA. Since U1-snRNA is enriched in apoptotic bodies and epithelial cells are capable of performing efferocytosis, the present data in particular connect to immunobiological aspects of apoptosis at host/environment interfaces