BackgroundEffective communication is critical for patient safety. One potential threat to communication in the operating room is incivility. Although examined in other industries, little has been done to examine how incivility impacts the ability to deliver safe care in a crisis. We therefore sought to determine how incivility influenced anaesthesiology resident performance during a standardised simulation scenario of occult haemorrhage.MethodsThis is a multicentre, prospective, randomised control trial from three academic centres. Anaesthesiology residents were randomly assigned to either a normal or ‘rude’ environment and subjected to a validated simulated operating room crisis. Technical and non-technical performance domains including vigilance, diagnosis, communication and patient management were graded on survey with Likert scales by blinded raters and compared between groups.Results76 participants underwent randomisation with 67 encounters included for analysis (34 control, 33 intervention). Those exposed to incivility scored lower on every performance metric, including a binary measurement of overall performance with 91.2% (control) versus 63.6% (rude) obtaining a passing score (p=0.009). Binary logistic regression to predict this outcome was performed to assess impact of confounders. Only the presence of incivility reached statistical significance (OR 0.110, 95% CI 0.022 to 0.544, p=0.007). 65% of the rude group believed the surgical environment negatively impacted performance; however, self-reported performance assessment on a Likert scale was similar between groups (p=0.112).ConclusionAlthough self-assessment scores were similar, incivility had a negative impact on performance. Multiple areas were impacted including vigilance, diagnosis, communication and patient management even though participants were not aware of these effects. It is imperative that these behaviours be eliminated from operating room culture and that interpersonal communication in high-stress environments be incorporated into medical training.

Objective This study aimed to evaluate the proportion of patients with seizures and electroencephalography (EEG) abnormalities in autoimmune encephalitis (AE) and its most common subtypes. Methods This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta‐Analysis (PRISMA) standards and was registered with the International Prospective Register of Systematic Reviews (PROSPERO). We searched Medline All, Embase, and PsychINFO in Ovid from inception to June 2019 for articles pertaining to AE and seizure. Included studies reported seizure and/or EEG data in cohorts of ≥10 AE patients. Patient demographics, antibody type, seizure incidence, and EEG findings were extracted. Review of studies and data extraction were performed in duplicate. In addition to descriptive analysis, quantitative synthesis stratified by autoantibody subtype was performed with logistic regression and chi‐square analyses. Results Our search yielded 3856 abstracts: 1616 were selected for full‐text review and 118 studies met eligibility criteria. Of 3722 antibody‐positive AE patients, 2601 (69.9%) had clinical seizures during the course of their illness. Of the 2025 patients with antibody‐positive AE and available EEG data, 1718 (84.8%) had some EEG abnormality (eg, epileptiform discharges, slowing, and so on). Anti‐ N‐methyl‐d‐aspartate (NMDA) receptor encephalitis (anti‐NMDARE) was the most commonly reported type of AE (1985/3722, 53.3%). Of the anti‐NMDARE patients with available seizure or EEG data, 71.8% (n = 1425/1985) had clinical seizures during their illness, and 89.7% (n = 1172/1306) had EEG abnormalities. For all AE patients and in the anti‐NMDARE subpopulation, seizures were more common in younger patients (p < .05). Significance This systematic review provides an estimate of the proportion of AE patients with seizures, confirming the magnitude of seizure burden in this population. Prospective studies are needed to understand population‐based prevalence of seizures, identify factors associated with seizures, and evaluate particular EEG findings as biomarkers of seizures and outcomes in AE.

The arginine vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including aggression, social learning and memory. Genetic removal of Avpr1b from mouse models results in deficits in aggression and short-term social recognition in adults. Avpr1b gene expression is highly enriched in the pyramidal neurons of the hippocampal cornu ammonis 2 (CA2) region. Activity of the hippocampal CA2 has been shown to be required for normal short-term social recognition and aggressive behaviors. Vasopressin acts to enhance synaptic responses of CA2 neurons through a NMDA-receptor dependent mechanism. Genetic removal of the obligatory subunit of the NMDA receptor (Grin1) within distinct hippocampal regions impairs non-social learning and memory. However, the question of a direct role for NMDA receptor activity in Avpr1b neurons to modulate social behavior remains unclear. To answer this question, we first created a novel transgenic mouse line with Cre recombinase knocked into the Avpr1b coding region to genetically target Avpr1b neurons. We confirmed this line has dense Cre expression throughout the dorsal and ventral CA2 regions of the hippocampus, along with scattered expression within the caudate-putamen and olfactory bulb (OB). Conditional removal of the NMDA receptor was achieved by crossing our line to an available floxed Grin1 line. The resulting mice were measured on a battery of social and memory behavioral tests. Surprisingly, we did not observe any differences between Avpr1b-Grin1 knockout mice and their wildtype siblings. We conclude that mice without typical NMDA receptor function in Avpr1b neurons can develop normal aggression as well as short-term social and object memory performance.

The vasopressin 1b receptor (Avpr1b) plays an important role in social behaviors including aggression, social learning and memory. Genetic removal of Avpr1b from mouse models results in deficits in aggression and short-term social recognition in adults. Avpr1b gene expression is highly enriched in the pyramidal neurons of the hippocampal cornu ammonis 2 (CA2) region. Activity of the hippocampal CA2 has been shown to be required for normal short-term social recognition and aggressive behaviors. Vasopressin acts to enhance synaptic responses of CA2 neurons through a NMDA-receptor dependent mechanism. Genetic removal of the obligatory subunit of the NMDA receptor (Grin1) within distinct hippocampal regions impairs non-social learning and memory. However, the question of a direct role for NMDA receptor activity in Avpr1b neurons to modulate social behavior remains unclear. To answer this question, we first created a novel transgenic mouse line with Cre recombinase knocked into the Avpr1b coding region to genetically target Avpr1b neurons. We confirmed this line has dense Cre expression throughout the dorsal and ventral CA2 regions of the hippocampus, along with scattered expression within the caudate-putamen and olfactory bulb. Conditional removal of the NMDA receptor was achieved by crossing our line to an available floxed Grin1 line. The resulting mice were measured on a battery of social and memory behavioral tests. Surprisingly, we did not observe any differences between Avpr1b-Grin1 knockout mice and their wildtype siblings. We conclude that mice without typical NMDA receptor function in Avpr1b neurons can develop normal aggression as well as short-term social and object memory performance.Significance StatementActivity of neurons that express vasopressin 1b receptor are essential for aggressive and social recognition behaviors. We created a novel transgenic mouse to allow selective targeting of vasopressin 1b neurons. Our studies indicate that NMDA receptor expression in vasopressin 1b neurons (including most CA2 neurons) are not required for development of the typical expression of aggression or recognition memory. Thus, CA2 neurons may have a unique way of incorporating novel stimuli into memory that deserves further investigation.

Background Phelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS. Methods Eighteen children aged 5–17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase, followed by a 12-week open-label extension phase during which all participants received oxytocin. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist-Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD. Safety was monitored throughout the study period. Results There was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann–Whitney U = 50, p = 0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated, and there were no serious adverse events. Limitations The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results. Conclusion Our results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS. Trial registration NCT02710084.

BackgroundPhelan-McDermid syndrome (PMS) is a rare neurodevelopmental disorder caused by haploinsufficiency of the SHANK3 gene and characterized by global developmental delays, deficits in speech and motor function, and autism spectrum disorder (ASD). Monogenic causes of ASD such as PMS are well suited to investigations with novel therapeutics, as interventions can be targeted based on established genetic etiology. While preclinical studies have demonstrated that the neuropeptide oxytocin can reverse electrophysiological, attentional, and social recognition memory deficits in Shank3-deficient rats, there have been no trials in individuals with PMS. The purpose of this study is to assess the efficacy and safety of intranasal oxytocin as a treatment for the core symptoms of ASD in a cohort of children with PMS.MethodsEighteen children aged 5-17 with PMS were enrolled. Participants were randomized to receive intranasal oxytocin or placebo (intranasal saline) and underwent treatment during a 12-week double-blind, parallel group phase followed by a 12-week open-label extension phase during which all participants received intranasal oxytocin. Safety was monitored throughout the study period and efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist – Social Withdrawal (ABC-SW) subscale as well as a number of secondary outcome measures related to the core symptoms of ASD.ResultsThere was no statistically significant improvement with oxytocin as compared to placebo on the ABC-SW (Mann-Whitney U=50, p=0.055), or on any secondary outcome measures, during either the double-blind or open-label phases. Oxytocin was generally well tolerated and there were no serious adverse events.Limitations: The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results.ConclusionOur results suggest that intranasal oxytocin is not efficacious in improving the core symptoms of ASD in children with PMS.Trial registration: NCT02710084

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