Management of the aggressive emergency department patient: Non-pharmacological perspectives and evidence base

Introduction: Aggression in the Emergency Department (ED) remains an ongoing issue, described as reaching epidemic proportions, with an impact on staff recruitment, retention, and ability to provide quality care. Most literature has focused on the definition (or lack of) core concepts, efforts to quantify the phenomenon or provide an epidemiological profile. Relatively little offers evidence-based interventions or evaluations of the same. Aim: To identify the range of suggested practices and the evidence base for currently recommended actions relating to the management of the aggressive Emergency Department patient. Methods: A meta-synthesis of existing reviews of violence and aggression in the acute health-care setting, including management of the aggressive patient, was undertaken. This provided the context for critical consideration of the management of this patient group in the ED and implications for clinical practice. Results: An initial outline of issues was followed by a systematic search and 15 reviews were further assessed. Commonly identified interventions are grouped around educational, interpersonal, environmental, and physical responses. These actions can be focused in terms of overall responses to the wider issues of violence and aggression, targeted at the pre-event, event, or post-event phase in terms of strategies; however, there is a very limited evidence base to show the effectiveness of strategies suggested. Clinical Implications: The lack of evidence-based intervention strategies leaves clinicians in a difficult situation, often enacting practices based on anecdote rather than evidence. Local solutions to local problems are occurring in a pragmatic manner, but there needs to be clarification and integration of workable processes for evaluating and disseminating best practice. Conclusion: There is limited evidence reporting on interventional studies, in addition to identification of the need for high quality longitudinal and evaluation studies to determine the efficacy of those responses that have been identified

A Plasmid-Transposon Hybrid Mutagenesis System Effective in a Broad Range of Enterobacteria.

Random transposon mutagenesis is a powerful technique used to generate libraries of genetic insertions in many different bacterial strains. Here we develop a system facilitating random transposon mutagenesis in a range of different Gram-negative bacterial strains, including Pectobacterium atrosepticum, Citrobacter rodentium, Serratia sp. ATCC39006, Serratia plymuthica, Dickeya dadantii, and many more. Transposon mutagenesis was optimized in each of these strains and three studies are presented to show the efficacy of this system. Firstly, the important agricultural pathogen D. dadantii was mutagenized. Two mutants that showed reduced protease production and one mutant producing the previously cryptic pigment, indigoidine, were identified and characterized. Secondly, the enterobacterium, Serratia sp. ATCC39006 was mutagenized and mutants incapable of producing gas vesicles, proteinaceous intracellular organelles, were identified. One of these contained a β-galactosidase transcriptional fusion within the gene gvpA1, essential for gas vesicle production. Finally, the system was used to mutate the biosynthetic gene clusters of the antifungal, anti-oomycete and anticancer polyketide, oocydin A, in the plant-associated enterobacterium, Dickeya solani MK10. The mutagenesis system was developed to allow easy identification of transposon insertion sites by sequencing, after facile generation of a replicon encompassing the transposon and adjacent DNA, post-excision. Furthermore, the system can also create transcriptional fusions with either β-galactosidase or β-glucuronidase as reporters, and exploits a variety of drug resistance markers so that multiple selectable fusions can be generated in a single strain. This system of various transposons has wide utility and can be combined in many different ways.The authors would like to acknowledge several funding sources. D. Smith was supported by a PhD studentship from the BBSRC. Work in the MW lab is supported by the BBSRC (grants BB/G015171/1 and BB/M019411/1). K. Roberts was funded by an MRC studentship. R. Monson and the Salmond lab were supported by grants from the BBSRC (Grant No Provisional BB/K001833/1). M.A. Matilla was supported by the EU Marie-Curie Intra-European Fellowship for Career Development (FP7-PEOPLE-2011-IEF), grant number 298003. B. Richardson was supported by a Harry Smith vacation studentship from the SGM, UK. The authors would also like to thank Ray Chai for careful reading and comments on this manuscript. Alison Drew provided technical support. Work with plant pathogens was carried out under DEFRA licence No. 50864/197900/1.This is the final version of the article. It was first available from Frontiers via http://dx.doi.org/10.3389/fmicb.2015.0144

Supervision and feedback for junior medical staff in Australian emergency departments: findings from the emergency medicine capacity assessment study

<p>Abstract</p> <p>Background</p> <p>Clinical supervision and feedback are important for the development of competency in junior doctors. This study aimed to determine the adequacy of supervision of junior medical staff in Australian emergency departments (EDs) and perceived feedback provided.</p> <p>Methods</p> <p>Semi-structured telephone surveys sought quantitative and qualitative data from ED Directors, Directors of Emergency Medicine Training, registrars and interns in 37 representative Australian hospitals; quantitative data were analysed with SPSS 15.0 and qualitative data subjected to content analysis identifying themes.</p> <p>Results</p> <p>Thirty six of 37 hospitals took part. Of 233 potential interviewees, 95 (40.1%) granted interviews including 100% (36/36) of ED Directors, and 96.2% (25/26) of eligible DEMTs, 24% (19/81) of advanced trainee/registrars, and 17% (15/90) of interns. Most participants (61%) felt the ED was adequately supervised in general and (64.2%) that medical staff were adequately supervised. Consultants and registrars were felt to provide most intern supervision, but this varied depending on shift times, with registrars more likely to provide supervision on night shift and at weekends. Senior ED medical staff (64%) and junior staff (79%) agreed that interns received adequate clinical supervision. Qualitative analysis revealed that good processes were in place to ensure adequate supervision, but that service demands, particularly related to access block and overcrowding, had detrimental effects on both supervision and feedback.</p> <p>Conclusions</p> <p>Consultants appear to provide the majority of supervision of junior medical staff in Australian EDs. Supervision and feedback are generally felt to be adequate, but are threatened by service demands, particularly related to access block and ED overcrowding.</p

Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders

Publisher's version: http://www.springerlink.com/content/rx24036274667t10

Ultrafast laser-scanning optical resolution photoacoustic microscopy at up to 2 million A-lines per second

The imaging speed of optical resolution photoacoustic microscopy (OR-PAM) using pulsed excitation is fundamentally limited by the range ambiguity condition, which defines the maximum laser pulse repetition frequency (PRF). To operate at this theoretical upper limit and maximize acquisition speed, a custom-built fiber laser capable of operating at a PRF of up to 2 MHz was combined with a fast laser scanning optical OR-PAM system based on a stationary fiber-optic ultrasound sensor. A large area (10 mm × 10 mm) of the mouse ear was imaged within 8 s, when acquiring 16 million A-lines and operating the laser at a PRF of 2 MHz. This corresponds to a factor of four improvement in imaging speed compared to the fastest OR-PAM system previously reported. The ability to operate at high-imaging frame rates also allows the capture of hemodynamic events such as blood flow. It is considered that this system offers opportunities for high throughput imaging and visualizing dynamic physiological events using OR-PAM

Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12

Chemokines and their ligands play a critical role in enabling chronic lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches within tissues, ultimately resulting in chemoresistance and relapse: disruption of these signaling pathways has become a novel therapeutic approach in CLL. The tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines from solid-organ tumours, but effects on CLL cells have not been reported. We studied the effect of clinically achievable concentrations of dasatinib on signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also significantly diminished the rapid increase in actin polymerisation observed in CLL cells following CXCL12 stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell assay, and reduced the percentage of cells able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest that dasatinib, akin to other small molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may redistribute CLL cells from protective tissue niches to the peripheral blood, and support the investigation of dasatinib in combination strategies

Metabolic, hygric and ventilatory physiology of a hypermetabolic marsupial, the honey possum (Tarsipes rostratus)

The honey possum is the only non-volant mammal to feed exclusively on a diet of nectar and pollen. Like other mammalian and avian nectarivores, previous studies indicated that the honey possum's basal metabolic rate was higher than predicted for a marsupial of equivalent body mass. However, these early measurements have been questioned. We re-examined the basal metabolic rate (2.52 +/- A 0.222 ml O(2) g(-1) h(-1)) of the honey possum and confirm that it is indeed higher (162%) than predicted for other marsupials both before and after accounting for phylogenetic history. This, together with its small body mass (5.4 +/- A 0.14 g; 1.3% of that predicted by phylogeny) may be attributed to its nectarivorous diet and mesic distribution. Its high-basal metabolic rate is associated with a high-standard body temperature (36.6 +/- A 0.48A degrees C) and oxygen extraction (19.4%), but interestingly the honey possum has a high point of relative water economy (17.0A degrees C) and its standard evaporative water loss (4.33 +/- A 0.394 mg H(2)O g(-1) h(-1)) is not elevated above that of other marsupials, despite its mesic habitat and high dietary water intake.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/