The Toll-like receptor 7 agonist imiquimod increases ethanol self-administration and induces expression of Toll-like receptor related genes.

There is growing evidence that immune signalling may be involved in both the causes and consequences of alcohol abuse. Toll-like receptor (TLR) expression is increased by alcohol consumption and is implicated in AUD, and specifically TLR7 may play an important role in ethanol consumption. We administered the TLR7-specific agonist imiquimod in male and female Long-Evans rats to determine (1) gene expression changes in brain regions involved in alcohol reinforcement, the nucleus accumbens core and anterior insular cortex, in rats with and without an alcohol history, and (2) whether TLR7 activation could modulate operant alcohol self-administration. Interferon regulatory factor 7 (IRF7) was dramatically increased in both sexes at both 2- and 24-h post-injection regardless of alcohol history and TLR3 and 7 gene expression was increased as well. The proinflammatory cytokine TNFα was increased 24-h post-injection in rats with an alcohol self-administration history, but this effect did not persist after four injections, suggesting molecular tolerance. Ethanol consumption was increased 24 h after imiquimod injections but did not occur until the third injection, suggesting adaptation to repeated TLR7 activation is necessary for increased drinking to occur. Notably, imiquimod reliably induced weight loss, indicating that sickness behaviour persisted across repeated injections. These findings show that TLR7 activation can modulate alcohol drinking in an operant self-administration paradigm and suggest that TLR7 and IRF7 signalling pathways may be a viable druggable target for treatment of AUD.

Implementation of the 'TAKE STOCK' Hot Debrief Tool in the ED: a quality improvement project.

Hot debriefing (HoD) describes a structured team-based discussion which may be initiated following a significant event. Benefits may include improved teamwork, staff well-being and identification of learning opportunities. Existing literature indicates that while staff value HoD following significant events, it is infrequently undertaken in practice. Internationally, several frameworks for HoD have been developed, although none are widely adopted for use in the ED. A quality improvement project was conducted to introduce HoD into a single UK ED in North West England, between January and March 2019. Following stakeholder consultation, the 9-item 'TAKE STOCK' tool was developed. Implementation of the tool increased the number of HoD (0-2.2 HoD episodes/week). Findings from the first plan-do-study-act (PDSA) cycle are presented, which revealed the key strengths and limitations of this model. Staff perceptions of the tool were evaluated using a self-administered short questionnaire designed by the authors. Satisfaction with TAKE STOCK was assessed using 10-point numerical scales. Across respondents (n-15), average satisfaction scores exceeded 9 out of 10 concerning patient care, staff self-care, decision-making, education, teamwork and identification of equipment issues. Implementation of HoD into the ED is feasible and viewed as beneficial by staff. Implementation toolkits for TAKE STOCK have been requested by 42 additional UK hospitals and ambulance trusts, demonstrating significant interest in its use. Research is now required to formally validate HoD frameworks for use in the ED, and assess whether HoD results in sustained improvements to staff and patient outcomes.