BackgroundThe Richmond Agitation-Sedation Scale (RASS), which assesses level of sedation and agitation, is a simple observational instrument which was developed and validated for the intensive care setting. Although used and recommended in palliative care settings, further validation is required in this patient population. The aim of this study was to explore the validity and feasibility of a version of the RASS modified for palliative care populations (RASS-PAL).MethodsA prospective study, using a mixed methods approach, was conducted. Thirteen health care professionals (physicians and nurses) working in an acute palliative care unit assessed ten consecutive patients with an agitated delirium or receiving palliative sedation. Patients were assessed at five designated time points using the RASS-PAL. Health care professionals completed a short survey and data from semi-structured interviews was analyzed using thematic analysis.ResultsThe inter-rater intraclass correlation coefficient range of the RASS-PAL was 0.84 to 0.98 for the five time points. Professionals agreed that the tool was useful for assessing sedation and was easy to use. Its role in monitoring delirium however was deemed problematic. Professionals felt that it may assist interprofessional communication. The need for formal education on why and how to use the instrument was highlighted.ConclusionThis study provides preliminary validity evidence for the use of the RASS-PAL by physicians and nurses working in a palliative care unit, specifically for assessing sedation and agitation levels in the management of palliative sedation. Further validity evidence should be sought, particularly in the context of assessing delirium.

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Macrophage-secreted factors inhibit adipogenesis, but the underlying mechanism is not well understood. Our objective was to determine if anti-adipogenic signaling pathways in human preadipocytes are activated by macrophage-conditioned medium (MacCM). Human abdominal subcutaneous stromal preadipocytes were treated with adipogenic inducers in either standard medium or medium conditioned by human THP-1 macrophages. THP-1-MacCM increased inhibitor of κB kinase β (IKKβ) phosphorylation, inhibitor of NF-κB α (IκBα) degradation, and NF-κB activity in human preadipocytes in a time-dependent manner. Concomitant treatment of human abdominal subcutaneous preadipocytes with sc-514, a selective inhibitor of IKKβ, prevented the inhibitory effect of THP-1-MacCM on lipid accumulation and expression of adipogenic markers. Our data indicate that activation of the preadipocyte IKKβ/NF-κB pathway is required for the anti-adipogenic effect of THP-1-MacCM on human adipogenesis.

Adipose tissue of obese individuals is characterized by increased fibrosis and macrophage infiltration. Extensive remodeling of the extracellular matrix (ECM) that occurs during adipogenesis can be influenced by macrophages, but it remains unclear how macrophage-secreted factors alter preadipocyte ECM protein expression under non-adipogenic versus adipogenic conditions. Confluent human subcutaneous abdominal preadipocytes were cultured for 14 days, with or without adipogenic inducers, in either control medium, medium conditioned by THP-1 monocytes (THP-1-MonCM), or medium conditioned by THP-1 macrophages (THP-1-MacCM). Under non-adipogenic conditions in THP-1-MacCM, collagen I/III and fibronectin protein levels rose by 40 and 70 %, respectively (p < 0.05, n = 3; compared to control non-adipogenic medium). When preadipocytes were exposed to adipogenic inducers in THP-1-MacCM, collagen I/III levels increased by 50 %, but those of fibronectin fell by 48 %, both compared to non-adipogenic THP-1-MacCM conditions. The rise in collagen I/III levels contrasts with the 51 % decrease in collagen I/III that occurs with induction of differentiation in control medium, whereas, the decrease in fibronectin is more modest, but consistent in THP-1-MacCM (48 %) and control medium (92 %). A similar effect on fibronectin levels occurred using medium conditioned by LPS-treated human monocyte-derived macrophages (MD-MacCM). Our data indicate macrophage-derived factors regulate levels of collagen I/III and fibronectin in preadipocytes under non-adipogenic and adipogenic conditions. Further studies are needed to determine if these changes in these ECM proteins contribute to the anti-adipogenic action of MacCM.