STOPTHEBURN: A Randomized Controlled Trial of Death Cafés for Burnout Prevention in ICU Employees.

RATIONALE: Effective interventions to prevent burnout among intensive care unit (ICU) clinicians are urgently needed. Death Cafés, group discussions about death, build a sense of community and create a space for reflection on distressing events. OBJECTIVE: To assess whether participation in regular Death Cafés can prevent burnout in ICU clinicians (physicians, nurses, pharmacists, therapists). METHODS: A randomized clinical trial was conducted from July 2020-December 2022 in ten ICUs in Louisiana. Subjects were randomized to attend four psychotherapist-facilitated, virtual Death Cafés or to a control arm. MEASUREMENTS AND MAIN RESULTS: The primary outcome was burnout defined by the Maslach Burnout Inventory-Human Services Survey (MBI-HSS) at 6 months. Depression and anxiety scores were measured as well as qualitative data on stressors, coping, and Death Café experience. Among 340 clinicians screened and consented (171 physicians; 169 non-physicians), 251 participated (mean age 31.06.8 years, 63% female, 72% white, 37% nurses, 27% residents, 25% interns, 11% other). Burnout prevalence was 19% at baseline. Of 136 participants who completed 6-month follow-up, no significant differences were found between intervention and control for the primary outcome (18% versus 25%, unadjusted OR 0.64 [95% CI 0.26-1.57], p=0.33). There were no differences in anxiety or depression. Notably, the study was limited by an inability to achieve target enrollment and high attrition rate (46%). CONCLUSIONS: Virtual Death Cafés were unable to reduce burnout, although the study was underpowered to detect differences between groups. Clinical trial registered with Clinicaltrials.gov (NCT04347811).

O-GlcNAc transferase regulates collagen deposition and fibrosis resolution in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease that is characterized by an excessive accumulation of extracellular matrix (ECM) proteins (e.g. collagens) in the parenchyma, which ultimately leads to respiratory failure and death. While current therapies exist to slow the progression, no therapies are available to resolve fibrosis. Methods: We characterized the O-linked N-Acetylglucosamine (O-GlcNAc) transferase (OGT)/O-GlcNAc axis in IPF using single-cell RNA-sequencing (scRNA-seq) data and human lung sections and isolated fibroblasts from IPF and non-IPF donors. The underlying mechanism(s) of IPF were further investigated using multiple experimental models to modulate collagen expression and accumulation by genetically and pharmacologically targeting OGT. Furthermore, we hone in on the transforming growth factor-beta (TGF-ß) effector molecule, Smad3, by co-expressing it with OGT to determine if it is modified and its subsequent effect on Smad3 activation. Results: We found that OGT and O-GlcNAc levels are upregulated in patients with IPF compared to non-IPF. We report that the OGT regulates collagen deposition and fibrosis resolution, which is an evolutionarily conserved process demonstrated across multiple species. Co-expression of OGT and Smad3 showed that Smad3 is O-GlcNAc modified. Blocking OGT activity resulted in decreased phosphorylation at Ser-423/425 of Smad3 attenuating the effects of TGF-ß1 induced collagen expression/deposition. Conclusion: OGT inhibition or knockdown successfully blocked and reversed collagen expression and accumulation, respectively. Smad3 is discovered to be a substrate of OGT and its O-GlcNAc modification(s) directly affects its phosphorylation state. These data identify OGT as a potential target in pulmonary fibrosis resolution, as well as other diseases that might have aberrant ECM/collagen accumulation.

Effects of Cannabidiol in Adolescent and Young Adult Depressive and Anxiety Disorders: A Systematic Review of Clinical and Preclinical Research.

Background: Adolescents and young adults may use cannabidiol (CBD) products in an attempt to reduce depression and anxiety symptoms, despite little research examining this use. This systematic review evaluated preclinical and clinical research on the effects of CBD on depressive and anxiety disorders in adolescence and young adulthood. To provide context, we discuss CBD's mechanism of action and neurodevelopmental effects. Methods: PubMed was searched for articles published through June 2022. Preclinical or clinical CBD administration studies with N > 1 that examined depressive and/or anxiety disorders were eligible. Results: Initially, 224 publications were identified. After excluding duplicates and applying eligibility criteria, 6 preclinical (depression: n≈133; anxiety: n≈161) and 4 clinical (anxiety: n=113) articles remained. Due to the low number of studies, results were synthesized qualitatively. The Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence were used to rate each study's evidence. The preclinical effects of CBD on depression-like behavior appear to differ by sex, early life stress, and duration of use. Despite no evidence that CBD exerts anxiolytic effects in preclinical adolescent models, CBD may reduce anxiety symptoms in human adolescents and young adults with anxiety disorders. Conclusions: The existing evidence suggests that CBD may reduce symptoms of anxiety in adolescents and young adults. However, the evidence is sparse and limited by variations in samples and CBD dosing duration. Further research is needed to understand the potential benefits and/or harms of CBD for depression and anxiety disorders in this population. Implications for clinical practice and research are discussed.