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Audience: The target audiences for this hands-on innovation are health care providers including medical students and emergency medicine residents. This simulation is also appropriate for small group sessions teaching the layperson., Background: While generally not life-threating fishhook injuries are commonplace. They can end a day of recreation or an outdoor trip and possibly result in a visit to an emergency department or urgent care. Hands-on education on fishhook removal techniques that minimize tissue damage is rarely provided in wilderness first aid or traditional medical education. To the best of our knowledge, to date there are only two studies on fishhook removal simulations in medical and wilderness first aid education.1,2 The previously described simulation models are limited by accessibility of materials, realism, and cost., Educational Objectives: The goal of this small group session is to fill the gap in training on fishhook injuries. At the end of the session participants should be able to describe the parts of a fishhook, as well as demonstrate and have increased confidence in performing multiple fishhook removal techniques., Educational Methods: Social learning theory is the conceptual framework for this small group session.3,4 This reflects the idea that students learn not only through repetition with trial and error, but through social interactions, observing and modeling successes of others. As a result, while this simulation requires a facilitator ensure the required items are available it does not necessitate a facilitator be present over the entire duration. Participants perform common fishhook removal techniques with hands-on skill development using commercially available silicone sponge injection pad trainers., Research Methods: Evaluating this small group session at a wilderness medicine training attended by medical and physician assistant students and their guests, self-reported confidence in fishhook removal before and after the simulation was assessed with a paired t-test. Survey results of perceived effectiveness and value of the simulation were also evaluated., Results: The average confidence increased 58% after the simulation (p<0.005). The mean level of effectiveness was 87% and the participant perceived monetary value of the simulation materials was greater than actual cost., Discussion: This innovation is a cost-friendly way to provide education and practice on fishhook removal. It requires minimal set up time and pre-learning can be easily modified to the expected knowledge and experience of participants. Understanding the fishhook removal techniques and increased levels of confidence has the potential to make participants more efficient when caring for patients. It may result in greater likelihood of success in removing fishhooks with minimal tissue damage., Topics: Fishhook injuries, medical simulation, emergency medical education, wilderness first aid, wound management, injection pad trainers., (© 2023 Baskin, et al.)

On 11th March 2020, the UK government announced plans for the scaling of COVID-19 testing, and on 27th March 2020 it was announced that a new alliance of private sector and academic collaborative laboratories were being created to generate the testing capacity required. The Cambridge COVID-19 Testing Centre (CCTC) was established during April 2020 through collaboration between AstraZeneca, GlaxoSmithKline, and the University of Cambridge, with Charles River Laboratories joining the collaboration at the end of July 2020. The CCTC lab operation focussed on the optimised use of automation, introduction of novel technologies and process modelling to enable a testing capacity of 22,000 tests per day. Here we describe the optimisation of the laboratory process through the continued exploitation of internal performance metrics, while introducing new technologies including the Heat Inactivation of clinical samples upon receipt into the laboratory and a Direct to PCR protocol that removed the requirement for the RNA extraction step. We anticipate that these methods will have value in driving continued efficiency and effectiveness within all large scale viral diagnostic testing laboratories., (© 2022. The Author(s).)

Objective: Providing comprehensive emergency preparedness training (EPT) to care providers is important to the future success of disaster operations in the US. Few EPT programs possess both competency-driven goals and metrics to measure performance during a multi-patient simulated disaster., Methods: A 1-day (8-hour) EPT course for care providers was developed to enhance provider knowledge, skill, and comfort necessary to save lives during a simulated disaster. Nine learning objectives, 18 competencies, and 34 performance objectives were developed. During the 2-year demonstration of the curriculum, 24 fourth-year medical students and 17 Veterans Hospital Administration (VHA) providers were recruited and volunteered to take the course (two did not fully complete the research materials). An online pre-test, two post-tests, course assessment, didactic and small group content, and a 6-minute clinical casualty scenario were developed. During the scenario, trainees working in teams were confronted with three human simulators and 10 actor patients simultaneously. Unless appropriate performance objectives were met, the simulators "died" and the team was exposed to "anthrax." After the scenario, team members participated in a facilitator-led debriefing using digital video and then repeated the scenario., Results: Trainees (N = 39) included 24 (62%) medical students; seven (18%) physicians; seven (18%) nurses; and one (3%) emergency manager. Forty-seven percent of the VHA providers reported greater than 16 annual hours of disaster training, while 15 (63%) of the medical students reported no annual disaster training. The mean (SD) score for the pre-test was 12.3 (3.8), or 51% correct, and after the training, the mean (SD) score was 18.5 (2.2), or 77% (P < .01). The overall rating for the course was 96 out of 100. Trainee self-assessment of "Overall Skill" increased from 63.3 out of 100 to 83.4 out of 100 and "Overall Knowledge" increased from 49.3 out of 100 to 78.7 out of 100 (P < .01). Of the 34 performance objectives during the disaster scenario, 23 were completed by at least half of the teams during their first attempt. All teams except one (8 of 9) could resuscitate two simulators and all teams (9 of 9) helped prevent anthrax exposure during their second scenario attempt., Conclusions: The 1-day EPT course for novice and experienced care providers recreated a multi-actor clinical disaster and enhanced provider knowledge, comfort level, and EPT skill. A larger-scale study, or multi-center trial, is needed to further study the impact of this curriculum and its potential to protect provider and patient lives.

Different signals in addition to the antigenic signal are required to initiate an immunological reaction. In the context of sulfamethoxazole allergy, the Ag is thought to be derived from its toxic nitroso metabolite, but little is known about the costimulatory signals, including those associated with dendritic cell maturation. In this study, we demonstrate increased CD40 expression, but not CD80, CD83, or CD86, with dendritic cell surfaces exposed to sulfamethoxazole (250-500 microM) and the protein-reactive metabolite nitroso sulfamethoxazole (1-10 microM). Increased CD40 expression was not associated with apoptosis or necrosis, or glutathione depletion. Covalently modified intracellular proteins were detected when sulfamethoxazole was incubated with dendritic cells. Importantly, the enzyme inhibitor 1-aminobenzotriazole prevented the increase in CD40 expression with sulfamethoxazole, but not with nitroso sulfamethoxazole or LPS. The enzymes CYP2C9, CYP2C8, and myeloperoxidase catalyzed the conversion of sulfamethoxazole to sulfamethoxazole hydroxylamine. Myeloperoxidase was expressed at high levels in dendritic cells. Nitroso sulfamethoxazole immunogenicity was inhibited in mice with a blocking anti-CD40L Ab. In addition, when a primary nitroso sulfamethoxazole-specific T cell response using drug-naive human cells was generated, the magnitude of the response was enhanced when cultures were exposed to a stimulatory anti-CD40 Ab. Finally, increased CD40 expression was 5-fold higher on nitroso sulfamethoxazole-treated dendritic cells from an HIV-positive allergic patient compared with volunteers. These data provide evidence of a link between localized metabolism, dendritic cell activation, and drug immunogenicity.

Drug-induced changes in expression of cytochrome P450 (P450) genes are a significant issue in the preclinical development of pharmaceuticals. For example, preclinically, P450 induction can affect safety studies by reducing the systemic exposure of a compound undergoing toxicological evaluation, thus limiting the exposure that can be safely investigated in patients. Therefore, the induction potential of candidate drugs has been studied as part of the drug development process, typically using protein and/or catalytic end points. However, measuring changes in the levels of mRNA using TaqMan technology offers the opportunity to investigate this issue with the advantages of better dynamic range and specific enzyme identification. Here, we describe the TaqMan application to study ex vivo the P450 gene induction in the rat. Initially, livers from rats dosed with the prototypic P450 inducers beta-napthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX), and clofibric acid (CLO) were analyzed for mRNA levels of CYP1A1, 1A2, 2B1, 2B2, 2E1, 3A2, 3A23, and 4A1 and compared with control animals. The maximum fold induction of mRNA varied: 2500-fold for CYP1A1 with BNF, 680-fold for CYP2B1 with PB, 59-fold for CYP3A23 with DEX, and 16-fold for CYP4A1 with CLO. This method was then applied to estimate the inductive potential of putative drug candidates undergoing rodent toxicological evaluation. We present a summary of these data that demonstrates the sensitivity and specificity of the TaqMan assay to distinguish between inducers and noninducers and that offers a highly specific alternative to the quantification of drug effects on P450 expression using immunodetection and substrate metabolism.

Deliberate self-harm patients who leave the acute hospital environment before the completion of psychiatric assessment have an increased risk of subsequent self-harm. We considered the available data on 50 premature self-discharges identified prospectively in a general hospital with a well-developed integrated-care pathway for self-harm patients, and compared them to a control group. The self-discharge group was found to be more likely to have attempted self-poisoning without alcohol intoxication or other forms or combinations of self-harm, and an absence of identifiable previous self-harm or prior contact with local specialist psychiatric services. The two groups showed no difference in age, sex, or area of residence based on community mental health team sectors. It is proposed that these findings indicate hypotheses for further studies of why people leave the hospital without adequate assessment, and how service design could be improved in order to help them.

The incorporation of information management and technology into healthcare environments has long been advocated, but resistance from clinicians and perceived financial constraints have laboured its successful implementation in many trusts. This article looks at the reasons behind these problems and highlights the benefits to patients of effective use of information technology in the delivery and documentation of patient care.