Excited Delirium: A Systematic Review.

OBJECTIVE: We aimed to clarify the definition, epidemiology, and pathophysiology of excited delirium syndrome (ExDS) and to summarize evidence-based treatment recommendations. METHODS: We conducted a systematic literature search of MEDLINE, Ovid, Web of Knowledge, and Cochrane Library for articles published to March 18, 2017. We also searched the gray literature (Google Scholar) and official police or medical expert reports to complete specific epidemiologic data. Search results and full-text articles were independently assessed by two investigators and agreements between reviewers assessed with K statistics. We classified articles by study type, setting, and evidence level. RESULTS: After reviewing the title and abstract of 3,604 references, we fully reviewed 284 potentially relevant references, from which 66 were selected for final review. Six contributed to the definition of ExDS, 24 to its epidemiology, 38 to its pathophysiology, and 27 to its management. The incidence of ExDS varies widely with medical or medicolegal context. Mortality is estimated to be as much as 8.3% to 16.5%. Patients are predominantly male. Male sex, young age, African-American race, and being overweight are independent risk factors. Pathophysiology hypotheses mostly implicate dopaminergic pathways. Most cases occur with psychostimulant use or among psychiatric patients or both. Proposed treatments are symptomatic, often with rapid sedation with benzodiazepines or antipsychotic agents. Ketamine is suggested as an alternative. CONCLUSION: The overall quality of studies was poor. A universally recognized definition is lacking, remaining mostly syndromic and based on clinical subjective criteria. High mortality rate may be due to definition inconsistency and reporting bias. Our results suggest that ExDS is a real clinical entity that still kills people and that has probably specific mechanisms and risk factors. No comparative study has been performed to conclude whether one treatment approach is preferable to another in the case of ExDS.

Missed opportunities: evolution of patients leaving without being seen or against medical advice during a six-year period in a Swiss tertiary hospital emergency department.

AIM: The study aimed at describing the evolution over a 6-year period of patients leaving the emergency department (ED) before being seen ("left without being seen" or LWBS) or against medical advice ("left against medical advice" or LAMA) and at describing their characteristics. METHODS: A retrospective database analysis of all adult patients who are admitted to the ED, between 2005 and 2010, and who left before being evaluated or against medical advice, in a tertiary university hospital. RESULTS: During the study period, among the 307,716 patients who were registered in the ED, 1,157 LWBS (0.4%) and 1,853 LAMA (0.9%) patients were identified. These proportions remained stable over the period. The patients had an average age of 38.5±15.9 years for LWBS and 41.9±17.4 years for LAMA. The median time spent in the ED before leaving was 102.4 minutes for the LWBS patients and 226 minutes for LAMA patients. The most frequent reason for LAMA was related to the excessive length of stay. CONCLUSION: The rates of LWBS and LAMA patients were low and remained stable. The patients shared similar characteristics and reasons for leaving were largely related to the length of stay or waiting time.

Protein phosphorylation corrects the folding defect of the neuroblastoma (S120G) mutant of human nucleoside diphosphate kinase A/Nm23-H1.

Human nucleoside diphosphate (NDP) kinase A is a 'house-keeping' enzyme essential for the synthesis of nonadenine nucleoside (and deoxynucleoside) 5'-triphosphate. It is involved in complex cellular regulatory functions including the control of metastatic tumour dissemination. The mutation S120G has been identified in high-grade neuroblastomas. We have shown previously that this mutant has a folding defect: the urea-denatured protein could not refold in vitro. A molten globule folding intermediate accumulated, whereas the wild-type protein folded and associated into active hexamers. In the present study, we report that autophosphorylation of the protein corrected the folding defect. The phosphorylated S120G mutant NDP kinase, either autophosphorylated with ATP as donor, or chemically prosphorylated by phosphoramidate, refolded and associated quickly with high yield. Nucleotide binding had only a small effect. ADP and the non-hydrolysable ATP analogue 5'-adenyly-limido-diphosphate did not promote refolding. ATP-promoted refolding was strongly inhibited by ADP, indicating protein dephosphorylation. Our findings explain why the mutant enzyme is produced in mammalian cells and in Escherichia coli in a soluble form and is active, despite the folding defect of the S120G mutant observed in vitro. We generated an inactive mutant kinase by replacing the essential active-site histidine residue at position 118 with an asparagine residue, which abrogates the autophosphorylation. The double mutant H118N/S120G was expressed in inclusion bodies in E. coli. Its renaturation stops at a folding intermediate and cannot be reactivated by ATP in vitro. The transfection of cells with this double mutant might be a good model to study the cellular effects of folding intermediates.