Co-occurring first-episode psychosis and borderline personality pathology in an early intervention for psychosis cohort.

INTRODUCTION: Borderline personality disorder (BPD) is common among people diagnosed with first episode of psychosis (FEP), but is often under-recognized and under-researched. This study aimed to determine: (i) the prevalence of borderline personality pathology (subthreshold features and categorical disorder) in a FEP cohort (termed FEP + BPP); (ii) demographic and clinical factors associated with FEP + BPP; (iii) the symptomatic and functional outcomes. METHODS: This study was conducted within the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen over the 30-month period between 2014 and 2016. BPP was evaluated by using the Structured Clinical Interview for DSM-IV Axis II Personality Questionnaire BPD criteria. RESULTS: In a cohort of 457 young people with a FEP (mean age 19.5 years, 56% male), 18.4% had borderline personality pathology (BPP). Compared with FEP alone, young people with FEP + BPP were more likely to be female, younger, Australian-born. In addition, young people with FEP + BPP were more likely to be diagnosed with Psychosis NOS, present with more severe hallucinations, and have alcohol abuse. Young people with FEP + BPP had more relationship difficulties at presentation and they were more likely to suffer of depression and to engage in self-harm throughout the follow-up. In relation to outcome, FEP + BPP was not associated with different rates of remission or relapse, however they were less likely to be admitted to hospital at presentation or involuntarily during their episode of care. CONCLUSION: BPP is a common occurrence in psychotic disorders and is associated with more severe hallucinations and depression with higher risks of self-harm. Specific interventions need to be developed.

Exposure and confidence across critical airway procedures in pediatric emergency medicine: An international survey study.

BACKGROUND: Airway management procedures are critical for emergency medicine (EM) physicians, but rarely performed skills in pediatric patients. Worldwide experience with respect to frequency and confidence in performing airway management skills has not been previously described. OBJECTIVES: Our aims were 1) to determine the frequency with which emergency medicine physicians perform airway procedures including: bag-mask ventilation (BMV), endotracheal intubation (ETI), laryngeal mask airway (LMA) insertion, tracheostomy tube change (TTC), and surgical airways, and 2) to investigate predictors of procedural confidence regarding advanced airway management in children. METHODS: A web-based survey of senior emergency physicians was distributed through the six research networks associated with Pediatric Emergency Research Network (PERN). Senior physician was defined as anyone working without direct supervision at any point in a 24-h cycle. Physicians were queried regarding their most recent clinical experience performing or supervising airway procedures, as well as with hands on practice time or procedural teaching. Reponses were dichotomized to within the last year, or ≥ 1 year. Confidence was assessed using a Likert scale for each procedure, with results for ETI and LMA stratified by age. Response levels were dichotomized to "not confident" or "confident." Multivariate regression models were used to assess relevant associations. RESULTS: 1602 of 2446 (65%) eligible clinicians at 96 PERN sites responded. In the previous year, 1297 (85%) physicians reported having performed bag-mask ventilation, 900 (59%) had performed intubation, 248 (17%) had placed a laryngeal mask airway, 348 (23%) had changed a tracheostomy tube, and 18 (1%) had performed a surgical airway. Of respondents, 13% of physicians reported the opportunity to supervise but not provide ETI, 5% for LMA and 5% for BMV. The percentage of physicians reporting "confidence" in performing each procedure was: BMV (95%) TTC (43%), and surgical airway (16%). Clinician confidence in ETT and LMA varied by patient age. Supervision of an airway procedure was the strongest predictor of procedural confidence across airway procedures. CONCLUSION: BMV and ETI were the most commonly performed pediatric airway procedures by emergency medicine physicians, and surgical airways are very infrequent. Supervising airway procedures may serve to maintain procedural confidence for physicians despite infrequent opportunities as the primary proceduralist.

Exposure and Confidence With Critical Nonairway Procedures: A Global Survey of Pediatric Emergency Medicine Physicians.

BACKGROUND: Children rarely experience critical illness, resulting in low exposure of emergency physicians (EPs) to critical procedures. Our primary objective was to describe senior EP confidence, most recent performance, and/or supervision of critical nonairway procedures. Secondary objectives were to compare responses between those who work exclusively in PEM and those who do not and to determine whether confidence changed for selected procedures according to increasing patient age. METHODS: Survey of senior EPs working in 96 emergency departments (EDs) affiliated with the Pediatric Emergency Research Networks. Questions assessed training, performance, supervision, and confidence in 11 nonairway critical procedures, including cardiopulmonary resuscitation (CPR), vascular access, chest decompression, and cardiac procedures. RESULTS: Of 2446 physicians, 1503 (61%) responded to the survey. Within the previous year, only CPR and insertion of an intraosseous needle had been performed by at least 50% of respondents: over 20% had performed defibrillation/direct current cardioversion. More than 50% of respondents had never performed or supervised ED thoracotomy, pericardiocentesis, venous cutdown, or transcutaneous pacing. Self-reported confidence was high for all patient age groups for CPR, needle thoracocentesis, tube thoracostomy, intraosseous needle insertion, and defibrillation/DC cardioversion. Confidence levels increased with increasing patient age for central venous and arterial line insertion. Respondents working exclusively in PEM were more likely to report being at least somewhat confident in defibrillation/DC cardioversion, intraosseous needle insertion, and central venous line insertion in particular age groups; however, they were less likely to be at least somewhat confident in ED thoracotomy and transcutaneous pacing. CONCLUSIONS: Cardiopulmonary resuscitation and intraosseous needle insertion were the only critical nonairway procedures performed by at least half of EPs within the previous year. Confidence was higher for these procedures, and needle and tube thoracostomy. These data may inform the development of continuing medical education activities to maintain pediatric procedural skills for emergency physicians.

Rapid response calls in inpatient psychiatric units.

OBJECTIVE: To assess the rates of serious medical issues on psychiatry wards by determining the rate, indication and outcomes of rapid response calls. METHOD: Using retrospective file review, information regarding rapid response calls during an 8-month period was analysed. RESULTS: Seventy-two rapid response calls were recorded; 7.5% of the admissions involved a rapid response call. Of patients who required a rapid response call, 88.6% had medical comorbidities. Also, 29.2% of rapid response calls required transfer to another ward. CONCLUSIONS: Patients on psychiatry wards frequently require urgent medical intervention. Improved collaboration and service planning between general medical and psychiatric service is required to improve clinical care and outcomes for this high-risk group.

Preferred learning modalities and practice for critical skills: a global survey of paediatric emergency medicine clinicians.

OBJECTIVE: To describe senior paediatric emergency clinician perspectives on the optimal frequency of and preferred modalities for practising critical paediatric procedures. METHODS: Multicentre multicountry cross-sectional survey of senior paediatric emergency clinicians working in 96 EDs affiliated with the Pediatric Emergency Research Network. RESULTS: 1332/2446 (54%) clinicians provided information on suggested frequency of practice and preferred learning modalities for 18 critical procedures. Yearly practice was recommended for six procedures (bag valve mask ventilation, cardiopulmonary resuscitation (CPR), endotracheal intubation, laryngeal mask airway insertion, defibrillation/direct current (DC) cardioversion and intraosseous needle insertion) by at least 80% of respondents. 16 procedures were recommended for yearly practice by at least 50% of respondents. Two procedures (venous cutdown and ED thoracotomy) had yearly practice recommended by <40% of respondents. Simulation was the preferred learning modality for CPR, bag valve mask ventilation, DC cardioversion and transcutaneous pacing. Practice in alternative clinical settings (eg, the operating room) was the preferred learning modality for endotracheal intubation and laryngeal mask insertion. Use of models/mannequins for isolated procedural training was the preferred learning modality for all other invasive procedures. Free-text responses suggested the utility of cadaver labs and animal labs for more invasive procedures (thoracotomy, intercostal catheter insertion, open surgical airways, venous cutdown and pericardiocentesis). CONCLUSIONS: Paediatric ED clinicians suggest that most paediatric critical procedures should be practised at least annually. The preferred learning modality depends on the skill practised; alternative clinical settings are thought to be most useful for standard airway manoeuvres, while simulation-based experiential learning is applicable for most other procedures.

Paediatric critical procedures in the emergency department: Incidence, trends and the physician experience.

OBJECTIVES: To analyse and provide current data surrounding paediatric critical procedures performed in three EDs of a single Victorian health network. METHODS: We conducted a retrospective study of every paediatric ED attendance requiring management in a resuscitation cubicle at three Victorian hospitals in 2013. The primary outcome measure was the frequency of each paediatric critical procedure performed in the ED during the 12 month study period. Additional outcome measures included details of the proceduralist and of patient presentations. RESULTS: Across the three EDs, there were 54,633 paediatric presentations during the study period. 5895 patients were assessed in a resuscitation cubicle and of these, only 37 presentations required one or more critical procedures (7/10,000 presentations). A total of 53 critical procedures were performed. 83% (n = 43) of emergency physicians did not perform a single paediatric critical procedure during the study period. Endotracheal intubation was the most commonly performed critical procedure with 40 attempts (74% of procedures); however, 83% of the full-time emergency physicians regularly exposed to paediatric presentations did not attempt or supervise a single paediatric intubation over the 12 months. 49% of patients who received a critical procedure were under 3 years of age and the most common diagnostic categories were seizure, respiratory and trauma. CONCLUSION: Critical procedures in children occur infrequently. Clinical exposure in the ED is therefore unreliable as the sole source of experience for critical procedures.

Subunit interface residues of glutathione S-transferase A1-1 that are important in the monomer-dimer equilibrium.

Alpha class glutathione S-transferase, isozyme A1-1, is a dimer (51 kDa) of identical subunits. Using the crystal structure, two main areas of subunit interaction were chosen for study: (1) the hydrophobic ball and socket comprised of Phe52 from one subunit fitting into a socket formed on the other subunit by Met94, Phe136, and Val139 and (2) the Arg/Glu region consisting of Arg69 and Glu97 from both subunits. We introduced substitutions of these residues, by site-directed mutagenesis, to evaluate the importance of each at the subunit interface and to determine if monomeric enzymes could be generated using single mutations. Mutating each residue of the socket region to alanine results in little change in the kinetic parameters, and all are dimeric enzymes. In contrast, when Phe52, the ball residue, is replaced with alanine, the enzyme has very low activity and a weight average molecular mass of 31.9 kDa, as determined by sedimentation equilibrium experiments. Substitutions for Glu97 which eliminate the charge cause no appreciable changes in the kinetic parameters or molecular mass. Eliminating the charge on Arg69 (as in R69Q) results in a dimeric enzyme; however, when the charge is reversed (as in R69E), the weight average molecular mass is greatly shifted toward that of the monomer (33 kDa) and the changes in kinetic parameters are reasonably small. We determined the molecular masses in the presence of glutathione for F52A and R69E to ascertain whether the monomeric species retains activity. For R69E, it appears that the monomer is active, albeit less so than the dimer, while for F52A, the monomer and dimer both appear to exhibit very low activity. The dimeric species is needed to obtain high specific activity. We conclude that, of the residues that were studied, Phe52 and Arg69 are the major determinants of dimer formation and a single mutation at either position substantially hinders dimerization. The use of a mutant glutathione S-transferase which retains activity yet has a greatly weakened tendency to dimerize (such as R69E) may be advantageous for certain applications of GST fusion proteins.

Alpha-complementation assay for HIV envelope glycoprotein-mediated fusion.

The fusion reaction mediated by viral envelope glycoproteins proceeds through an ordered series of conformational changes in the envelope glycoprotein. Fusion inhibitors have been developed that target glycoprotein subunits, arresting the reaction at different points in the process. We report the development of a novel method for detecting viral glycoprotein-mediated fusion that is based on the principle of alpha-complementation of beta-galactosidase. The method is simple, accurate, has a high signal-to-noise ratio, is suited for high-throughput screening, and does not require new transcription or protein synthesis. Cells expressing a viral envelope glycoprotein and the N-terminal alpha fragment of beta-galactosidase were mixed with cells expressing the C-terminal beta-galactosidase fragment, CD4, CCR5, or CXCR4. Fusion was detected after 30 min and continued to increase to very high levels for more than 5 h. The assay was used to examine the temperature dependence of fusion and the effect of coreceptor and glycoprotein density on inhibitor activity.