Feasibility of ultrasound-guided nerve blocks in simulated microgravity: a proof-of-concept study for regional anaesthesia during deep space missions.

BACKGROUND: With crewed deep space exploration on the horizon, preparation for potential astronaut health crises in space missions has become vital. Administration of anaesthesia and analgesia presents many challenges owing to constraints specific to space (physiologic and ergonomic challenges associated with microgravity) and nonspecific factors (isolation and lack of supplies). Regional anaesthesia can be the safest option; however, we hypothesised that the ergonomics of microgravity would compromise ease and accuracy of nerve blocks. METHODS: We evaluated the feasibility of regional anaesthesia in a simulated microgravity environment (free-floating underwater conditions) using a meat (bovine muscle) model. Forty meat models were randomised for injection under simulated microgravity or normal gravity conditions. Success rates were determined by blinded assessors after injection. Parameters assessed included time to block, ease of image acquisition, and ease of needle placement. RESULTS: The median time to block in normal gravity was 27 (interquartile range 21-69) s vs 35 (interquartile range 22-48) s in simulated microgravity (P=0.751). Ease of image acquisition was similar in both conditions, as was ease of needle placement. There was no significant difference in the rate of accidental intraneural injections (5% vs 5%), with block success rates comparable in both scenarios (80% normal gravity vs 85% microgravity, P>0.999). CONCLUSIONS: Regional anaesthesia appears feasible for experts in simulated microgravity despite the ergonomic challenges. Although our model has limitations and might not fully capture the complexities of actual space conditions, it provides a foundation for future research into anaesthesia and analgesia during deep space missions.

Simulation-based ultrasound-guided regional anesthesia education: a national survey of Canadian anesthesiology residency training programs.

PURPOSE: Simulation-based education in ultrasound-guided regional anesthesia (UGRA) improves knowledge, skills, and patient outcomes. Nevertheless, it is not known how simulation-based UGRA education is used across Canada. We aimed to characterize the current use of simulation-based UGRA education in Canadian anesthesiology residency training programs. METHODS: We developed and distributed a structured national survey to simulation leads of all 17 Canadian anesthesiology residency training programs. The survey inquired about program demographics, simulation modalities, facilitators and barriers to simulation use, use for assessment, and beliefs around simulation-based UGRA education. We gathered data from August to November 2023 and summarized our findings descriptively. RESULTS: Fifteen programs (88%) responded to our survey. Eight programs (53%) used UGRA simulation for technical training and nine programs (60%) for nontechnical training. The most common simulators used were live model scanning (13 programs, 87%) and gel phantom models (7 programs, 47%). Five programs (33%) mandated simulation-based UGRA in their curriculum. We found that deliberate practice and improved patient safety were most valued in simulation training while lack of funding and faculty availability were the most common barriers to implementation. Most respondents agreed that formative simulation-based education would improve trainee skills and called for greater standardization. Nevertheless, there were mixed responses regarding summative UGRA simulation and the need for simulation proficiency before clinical practice. CONCLUSIONS: Our findings show significant variations in simulation implementation and views on UGRA simulation-based education among Canadian anesthesiology residency training programs. Future studies should explore avenues to overcome barriers and improve knowledge translation in UGRA.

RéSUMé: OBJECTIF: La formation basée sur la simulation en anesthésie régionale échoguidée améliore les connaissances, les compétences et les issues pour les patient·es. Néanmoins, on ne sait pas comment la formation en AR échoguidée basée sur la simulation est utilisée au Canada. Nous avons cherché à caractériser l'utilisation actuelle de l'enseignement de l'AR échoguidée basée sur la simulation dans les programmes canadiens de résidence en anesthésiologie. MéTHODE: Nous avons élaboré et distribué un sondage national structuré aux responsables de la simulation des 17 programmes canadiens de résidence en anesthésiologie. L'enquête portait sur les données démographiques du programme, les modalités de simulation, les facilitateurs et les obstacles à l'utilisation de la simulation, son utilisation pour l'évaluation, et les croyances concernant l'éducation en AR échoguidée basée sur la simulation. Nous avons recueilli des données d'août à novembre 2023 et résumé nos résultats de manière descriptive. RéSULTATS: Quinze programmes (88 %) ont répondu à notre sondage. Huit programmes (53 %) utilisent la simulation en AR échoguidée pour la formation technique et neuf programmes (60 %) pour la formation non technique. Les simulateurs les plus couramment utilisés étaient le balayage sur modèles vivants (13 programmes, 87 %) et les modèles de fantômes en gel (7 programmes, 47 %). Cinq programmes (33 %) ont rendu obligatoire l'AR échoguidée basée sur la simulation dans leur programme. Nous avons constaté que la pratique délibérée et l'amélioration de la sécurité des patient·es étaient les plus appréciées dans la formation par simulation, tandis que le manque de financement et la disponibilité du corps professoral étaient les obstacles les plus courants à la mise en œuvre. La plupart des répondant·es ont convenu que l'éducation formative basée sur la simulation améliorerait les compétences des stagiaires et ont appelé à une plus grande standardisation. Néanmoins, les réponses étaient mitigées concernant la simulation sommative en AR échoguidée et la nécessité d'une maîtrise de la simulation avant la pratique clinique. CONCLUSION: Nos résultats montrent des variations significatives dans la mise en œuvre de la simulation et les points de vue sur l'éducation basée sur la simulation en AR échoguidée parmi les programmes canadiens de résidence en anesthésiologie. Les études futures devraient explorer les moyens de surmonter les obstacles et d'améliorer l'application des connaissances à l'anesthésie régionale échoguidée.

A Mixed-Methods Cohort Study Evaluating the Impact of a One-Day Well-Being Course for Anesthesia Providers Working in Low-Resource Settings.

BACKGROUND: Burnout, depression, and anxiety are increasingly recognized as common among health care providers. Risks for these conditions are exacerbated in low-resource settings by excessive workload, high disease burden, resource shortage, and stigma against mental health issues. Based on discussions and requests to learn more about burnout during the Vital Anaesthesia Simulation Training (VAST), our team developed VAST Wellbeing, a 1-day course for health care providers in low-resource settings to recognize and mitigate burnout and to promote personal and professional well-being. METHODS: This mixed-methods study used quantitative pre- and postcourse surveys using validated mental health measures and qualitative semistructured interviews to explore participants' experience of VAST Wellbeing during and after the course. Quantitative outcomes included burnout and professional fulfillment as measured by the Professional Fulfillment Index and general well-being as measured by the Warwick-Edinburgh Mental Wellbeing Scale. RESULTS: Twenty-six participants from 9 countries completed the study. In the immediate postcourse survey, study participants rated the course overall as "very good" (60.7%) and "excellent" (28.6%). Quantitative analysis showed no statistical differences in levels of work exhaustion, interpersonal disengagement, burnout, professional fulfillment, or general mental well-being 2 months after the course. Five themes on the impact of VAST Wellbeing were identified during qualitative analysis: (1) raising awareness, breaking taboos; (2) not feeling alone; (3) permission and capacity for personal well-being; (4) workplace empowerment; and (5) VAST Wellbeing was relevant, authentic, and needed. CONCLUSIONS: Causes of burnout are complex and multidimensional. VAST Wellbeing did not change measures of burnout and fulfillment 2 months postcourse but did have a meaningful impact by raising awareness, reducing stigma, fostering connection, providing skills to prioritize personal well-being, and empowering people to seek workplace change.

Discriminative Ability of Dye Injected Into a Meat Model to Determine Accuracy of Ultrasound-Guided Injection.

INTRODUCTION: The utility of using meat models for ultrasound-guided regional anesthesia simulation training has been well established. Feedback is considered the most important element of successful simulation-based education, and simulation offers an opportunity for evaluation. The objective of this study was to establish the discriminative ability of dye injected into a meat model to determine whether injectate is properly placed in the perineural (PN) space, thus providing an additional tool for learner feedback and evaluation. METHODS: Meat models containing a beef tendon (simulating a nerve) were injected with dye in one of 3 locations: PN, intraneural, and intramuscular. Blinded assessors then independently interpreted the dye staining on the models, marked the interpreted injection location, ease of interpretation, and whether staining was present on the beef tendon. RESULTS: Thirty meat models were injected with dye and independently assessed. Determining the location of injection was deemed to be easy or very easy in 72% of the models. Assessors correctly identified PN, intraneural, and intramuscular injections 100%, 95%, and 85% of the time, respectively. Assessor agreement was 87%. CONCLUSIONS: The location of dye injected into a meat model, simulating a peripheral nerve blockade, can be accurately and reliably scored to provide feedback to learners. This technique offers a novel means of providing feedback to trainees and assessing block success in ultrasound-guided regional anesthesia simulation.

Computational Design of Cyclic Peptide Inhibitors of a Bacterial Membrane Lipoprotein Peptidase.

There remains a critical need for new antibiotics against multi-drug-resistant Gram-negative bacteria, a major global threat that continues to impact mortality rates. Lipoprotein signal peptidase II is an essential enzyme in the lipoprotein biosynthetic pathway of Gram-negative bacteria, making it an attractive target for antibacterial drug discovery. Although natural inhibitors of LspA have been identified, such as the cyclic depsipeptide globomycin, poor stability and production difficulties limit their use in a clinical setting. We harness computational design to generate stable de novo cyclic peptide analogues of globomycin. Only 12 peptides needed to be synthesized and tested to yield potent inhibitors, avoiding costly preparation of large libraries and screening campaigns. The most potent analogues showed comparable or better antimicrobial activity than globomycin in microdilution assays against ESKAPE-E pathogens. This work highlights computational design as a general strategy to combat antibiotic resistance.

Dive Hazards: Barotrauma, Flora, Fauna, Equipment, and Free Diving.

ABSTRACT: Present-day diving comes in various forms, from utilizing sophisticated diving equipment to relying solely on one's ability to hold their breath. The diver and physician must be aware of the many common medical conditions and environmental considerations of this unique activity. While barotrauma remains the most common dive-related injury, injuries and accidents also are related to diving equipment-related accidents and exposure to marine flora and fauna. In addition, breath-hold diving, which includes free diving, snorkeling, and tasks, is an activity humans have done for thousands of years for recreation or survival. This article will update the dangers of diving and methods to prevent or treat injuries.

Epidemiology of Craniomaxillofacial Fractures Over a 5-year Period at a Midwestern Level 1 Trauma Center Serving a Large Rural Population.

BACKGROUND: Though the epidemiology of craniomaxillofacial (CMF) fractures has been well documented at urban hospitals, the characteristics of these fractures in rural hospitals have not been well studied. PURPOSE: The purpose of this study is to report on the epidemiology of CMF fractures at a regional Level 1 trauma center serving a large rural population in central Illinois. STUDY DESIGN, SETTING, SAMPLE: This is a retrospective cohort study at a community-based regional tertiary referral center that serves a predominantly rural population. Inclusion criteria comprised patients with radiologically confirmed CMF fractures between 2015 and 2019. Patients with incomplete medical records were excluded. PREDICTOR VARIABLE: Predictor variables included demographics (age, admission source, race, and sex) and etiology of CMF fracture (assault/domestic violence, all-terrain vehicle/off-road, falls, farm-related, motor vehicle collisions, gunshot wound, and others). MAIN OUTCOME VARIABLE: The primary outcome variable was the CMF anatomic location including nasal bone, orbit, mandible, malar/maxillary, and other CMF fractures. COVARIATES: The covariates are not applicable. ANALYSES: Descriptive statistics were used to summarize a sample of the population characteristics. Wilcoxon ranked sign tests and χ2 tests of independence were used to assess for statistically significant associations between select variables of interest. Statistical significance was defined as P < .05. RESULTS: Between 2015 and 2019, a total of 2,334 patients presented to the emergency department with a CMF fracture. After applying the inclusion/exclusion criteria, the final sample was composed of 1,844 patients for the management of 2,405 CMF fractures. The majority of patients were male(62.0%) and young adults (aged 18-39) had the highest number of CMF fractures (819) relative to all other age groups. The most common fracture etiology was fall(37.3%), and nasal bone fractures represented the most common fracture location(41.6%). χ2 analyses revealed statistically significant associations between the anatomic location of CMF fracture incurred, and differing categories of age, admission source, race, sex, and etiology. CONCLUSION AND RELEVANCE: Our study shows that patients seen at our Midwestern Level 1 trauma center are more likely to present with nasal bone and malar/maxillary fractures due to falls. In studies based in urban centers, patients are likely to present with orbital and mandibular fractures due to falls and assault.

Association between anesthesia technique and death after hip fracture repair for patients with COVID-19.

PURPOSE: Patients with COVID-19 undergoing hip fracture surgeries have a 30-day mortality of up to 34%. We aimed to evaluate the association between anesthesia technique and 30-day mortality after hip fracture surgery in patients with COVID-19. METHODS: After ethics approval, we performed a retrospective cohort analysis of the American College of Surgeons National Surgical Quality Improvement Program data set from January to December 2021. Inclusion criteria were age ≥ 19 yr, laboratory-confirmed SARS-CoV-2 infection within 14 days preoperatively, and hip fracture surgery under general anesthesia (GA) or spinal anesthesia (SA). Exclusion criteria were American Society of Anesthesiologists Physical Status V, ventilator dependence, international normalized ratio ≥ 1.5, partial thromboplastin time > 35 sec, and platelet count < 80 × 109 L-1. The primary outcome was all-cause 30-day mortality. The adjusted association between anesthetic technique and 30-day mortality was analyzed using multivariable logistic regression. RESULTS: Of 23,045 patients undergoing hip fracture surgery, 331 patients met the study criteria. The median [interquartile range] age was 82 [74-88] yr, and 32.3% were male. The 30-day mortality rate was 10.0% (33/331) for the cohort (10.7%, 29/272 for GA vs 6.8%, 4/59 for SA; P = 0.51; standardized mean difference, 0.138). The use of SA, compared with GA, was not associated with decreased mortality (adjusted odds ratio, 0.61; 95% confidence interval, 0.21 to 1.8; E-value, 2.49). CONCLUSION: Anesthesia technique was not associated with mortality in patients with COVID-19 undergoing hip fracture surgery. The findings were limited by a small sample size. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT05133648); registered 24 November 2021.

RéSUMé: OBJECTIF: Les personnes atteintes de COVID-19 bénéficiant d'une chirurgie de fracture de la hanche ont une mortalité à 30 jours allant jusqu'à 34 %. Notre objectif était d'évaluer l'association entre la technique d'anesthésie et la mortalité à 30 jours après une chirurgie de fracture de la hanche chez les personnes atteintes de COVID-19. MéTHODE: Après l'approbation du comité d'éthique, nous avons réalisé une analyse de cohorte rétrospective de l'ensemble de données du Programme national d'amélioration de la qualité chirurgicale de l'American College of Surgeons de janvier à décembre 2021. Les critères d'inclusion étaient un âge ≥ 19 ans, une infection par le SRAS-CoV-2 confirmée en laboratoire dans les 14 jours préopératoires et une chirurgie de fracture de la hanche sous anesthésie générale (AG) ou rachianesthésie (RA). Les critères d'exclusion étaient un statut physique V selon l'American Society of Anesthesiologists, la dépendance à une assistance ventilatoire, un ratio international normalisé ≥ 1,5, un temps de thromboplastine partielle > 35 sec, et une numération plaquettaire < 80 × 109 L−1. Le critère d'évaluation principal était la mortalité à 30 jours toutes causes confondues. L'association ajustée entre la technique anesthésique et la mortalité à 30 jours a été analysée à l'aide d'une régression logistique multivariée. RéSULTATS: Sur 23 045 patient·es opéré·es pour une fracture de la hanche, 331 répondaient aux critères de l'étude. L'âge médian (écart interquartile) était de 82 [74­88] ans et 32,3 % étaient des hommes. Le taux de mortalité à 30 jours était de 10,0 % (33/331) pour la cohorte (10,7 %, 29/272 pour l'AG vs 6,8 %, 4/59 pour la RA; P = 0,51; différence moyenne standardisée, 0,138). L'utilisation de la RA, par rapport à l'AG, n'a pas été associée à une diminution de la mortalité (rapport de cotes ajusté, 0,61; intervalle de confiance à 95 %, 0,21 à 1,8; valeur E, 2,49). CONCLUSION: La technique d'anesthésie n'a pas été associée à la mortalité chez les personnes atteintes de COVID-19 bénéficiant d'une chirurgie de fracture de la hanche. Les résultats ont été limités par la petite taille de l'échantillon. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT05133648); enregistrée le 24 novembre 2021.

Comparative efficacy and safety of non-neuraxial analgesic techniques for midline laparotomy: a systematic review and frequentist network meta-analysis of randomised controlled trials.

BACKGROUND: Fascial plane blocks provide effective analgesia after midline laparotomy; however, the most efficacious technique has not been determined. We conducted a systematic review and network meta-analysis of randomised controlled trials to synthesise the evidence with respect to pain, opioid consumption, and adverse events. METHODS: We searched Ovid MEDLINE, Embase, Cochrane Central, and Scopus databases for studies comparing commonly used non-neuraxial analgesic techniques for midline laparotomy in adult patients. The co-primary outcomes of the study were 24-h cumulative opioid consumption and 24-h resting pain score, reported as i.v. morphine equivalents and 11-point numerical rating scale, respectively. We performed a frequentist meta-analysis using a random-effects model and a cluster-rank analysis of the co-primary outcomes. RESULTS: Of 6115 studies screened, 67 eligible studies were included (n=4410). Interventions with the greatest reduction in 24-h cumulative opioid consumption compared with placebo/no intervention were single-injection quadratus lumborum block (sQLB; mean difference [MD] -16.1 mg, 95% confidence interval [CI] -29.9 to -2.3, very low certainty), continuous transversus abdominis plane block (cTAP; MD -14.0 mg, 95% CI -21.6 to -6.4, low certainty), single-injection transversus abdominis plane block (sTAP; MD -13.7 mg, 95% CI -17.4 to -10.0, low certainty), and continuous rectus sheath block (cRSB; MD -13.2 mg, 95% CI -20.3 to -6.1, low certainty). Interventions with the greatest reduction in 24-h resting pain score were cRSB (MD -1.2, 95% CI -1.8 to -0.6, low certainty), cTAP (MD -1.0, 95% CI -1.7 to -0.2, low certainty), and continuous wound infusion (cWI; MD -0.7, 95% CI -1.1 to -0.4, low certainty). Clustered-rank analysis including the co-primary outcomes showed cRSB and cTAP blocks to be the most efficacious interventions. CONCLUSIONS: Based on current evidence, continuous rectus sheath block and continuous transversus abdominis plane block were the most efficacious non-neuraxial techniques at reducing 24-h cumulative opioid consumption and 24-h resting pain scores after midline laparotomy (low certainty). Future studies should compare techniques for upper vs lower midline laparotomy and other non-midline abdominal incisions. CLINICAL TRIAL REGISTRATION: PROSPERO Registration Number: CRD42021269044.

Pandemic-related factors predicting physician burnout beyond established organizational factors: cross-sectional results from the COPING survey.

The COVID-19 pandemic has increased physician burnout beyond high baseline levels. We aimed to determine whether pandemic-related factors contribute to physician burnout beyond known organizational factors. This was a cross-sectional survey of Canadian physicians using a convenience sample. Eligible participants included any physician currently holding a license to practice in Canada. Responses were gathered from May 13 to 12 June 2020. Risk factors measured included the newly developed Pandemic Experiences and Perceptions Scale (PEPS) subscales, contact with virus, pandemic preparation, and provincial caseload. The primary outcome was the Maslach Burnout Inventory (MBI). The primary outcome was completed by 309 respondents. Latent profile analysis found 107 (34.6%) respondents were burned out. In multivariate analysis, exhaustion was independently associated with PEPS adequacy, risk perception, and worklife subscales (adjusted R2 = 0.236, P < 0.001). Cynicism was associated with exhaustion, and PEPS worklife (adjusted R2 = 0.543, P < 0.001). Efficacy was associated with cynicism, PEPS worklife, and active cases (adjusted R2 = 0.152, P < 0.001). Structural equation modelling showed statistically significant direct paths between PEPS areas of worklife and all MBI subscales. Contact with virus, preparation, and PEPS risk perception added to the prediction of MBI exhaustion. Among a sample of Canadian physicians during the COVID-19 pandemic, adequacy of resources, risk perception, and quality of worklife were associated with burnout indices. To mitigate physician burnout organizations should work to improve working conditions, ensure adequate resources, and foster perceived control of risk of transmission.Trial Registration: NCT04379063.

Cost comparison between spinal versus general anesthesia for hip and knee arthroplasty: an incremental cost study.

PURPOSE: Wait list times for total joint arthroplasties have been growing, particularly in the aftermath of the COVID-19 pandemic. Increasing operating room (OR) efficiency by reducing OR time and associated costs while maintaining quality allows the greatest number of patients to receive care. METHODS: We used propensity score matching to compare parallel processing with spinal anesthesia in a block room vs general anesthesia in a retrospective cohort of adult patients undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). We compared perioperative costs, hospital costs, OR time intervals, and complications between the groups with nonparametric tests using an intention-to-treat approach. RESULTS: After matching, we included 636 patients (315 TKA; 321 THA). Median [interquartile range (IQR)] perioperative costs were CAD 7,417 [6,521-8,109], and hospital costs were CAD 10,293 [9,344-11,304]. Perioperative costs were not significantly different between groups (pseudo-median difference [MD], CAD -47 (95% confidence interval [CI], -214 to -130; P = 0.60); nor were total hospital costs (MD, CAD -78; 95% CI, -340 to 178; P = 0.57). Anesthesia-controlled time and total intraoperative time were significantly shorter for spinal anesthesia (MD, 14.6 min; 95% CI, 13.4 to 15.9; P < 0.001; MD, 15.9; 95% CI, 11.0 to 20.9; P < 0.001, respectively). There were no significant differences in complications. CONCLUSION: Spinal anesthesia in the context of a dedicated block room reduced both anesthesia-controlled time and total OR time. This did not translate into a reduction in incremental cost in the spinal anesthesia group.

RéSUMé: OBJECTIF: Les temps d'attente pour les arthroplasties articulaires totales ont augmenté, en particulier à la suite de la pandémie de COVID-19. Une augmentation de l'efficacité de la salle d'opération (SOP) fondée sur une réduction du temps en salle d'opération et des coûts associés, tout en maintenant la qualité, permettrait à un plus grand nombre de patients de recevoir des soins. MéTHODE: Nous avons utilisé l'appariement par score de propension pour comparer en parallèle des traitements par rachianesthésie dans une salle de bloc vs par anesthésie générale dans une cohorte rétrospective de patients adultes bénéficiant d'une arthroplastie totale de la hanche (ATH) et d'une arthroplastie totale du genou (ATG) primaires. Nous avons comparé les coûts périopératoires, les coûts hospitaliers, les intervalles de temps en SOP et les complications entre les groupes avec des tests non paramétriques en utilisant une approche d'intention de traiter. RéSULTATS: Après appariement, nous avons inclus 636 patients (315 ATG; 321 ATH). Les coûts périopératoires médians [écart interquartile (ÉIQ)] étaient de 7417 $ CA [6521 ­ 8109] et les coûts hospitaliers de 10 293 $ CA [9344 ­ 11 304]. Les coûts périopératoires n'étaient pas significativement différents entre les groupes (différence pseudomédiane [DM], −47 $ CA (intervalle de confiance à 95 % [IC], −214 à −130; P = 0,60), pas plus que les coûts hospitaliers totaux (DM, −78 $ CA; IC 95 %, −340 à 178; P = 0,57). Le temps sous anesthésie et le temps peropératoire total étaient significativement plus courts pour la rachianesthésie (DM, 14,6 min; IC 95 %, 13,4 à 15,9; P < 0,001; DM, 15,9; IC 95 %, 11,0 à 20,9; P < 0,001, respectivement). Aucune différence significative n'a été observée dans les complications. CONCLUSION: La rachianesthésie dans un contexte de salle de bloc dédiée a réduit à la fois le temps sous anesthésie et le temps total de SOP. Cela ne s'est pas traduit par une réduction du coût différentiel dans le groupe recevant une rachianesthésie.

Cluster Headache: Rapid Evidence Review.

Cluster headache, the most common form of trigeminal autonomic cephalgia, is a rare primary headache disorder that affects less than 1% of the population. The mean age of onset is 30 years, and it is two to three times more common in males. Cluster headache consists of attacks of severe unilateral pain located in the orbital, supraorbital, and/or temporal region that occur from every other day up to eight times per day and last from 15 to 180 minutes. The pain is associated with ipsilateral autonomic symptoms (most commonly lacrimation, conjunctival injection, nasal congestion or rhinorrhea, ptosis, edema of the eyelid, sweating of the forehead or face, and miosis) and a sense of agitation or restlessness. Attacks occur in clusters, called bouts, and are episodic or chronic. Common triggers include alcohol, nitroglycerin, food containing nitrates, and strong odors. Abortive treatments include triptans and oxygen; transitional treatments include steroids and suboccipital steroid injections; and prophylactic treatments include verapamil, lithium, melatonin, and topiramate. Newer treatments for cluster headache include galcanezumab, neurostimulation, and somatostatin receptor agonists.

Human Mat2A Uses an Ordered Kinetic Mechanism and Is Stabilized but Not Regulated by Mat2B.

Methionine adenosyltransferase (MAT) catalyzes the adenosine 5'-triphosphate (ATP) and l-methionine (l-Met) dependent formation of S-adenosyl-l-methionine (SAM), the principal methyl donor of most biological transmethylation reactions. We carried out in-depth kinetic studies to further understand its mechanism and interaction with a potential regulator, Mat2B. The initial velocity pattern and results of product inhibition by SAM, phosphate, and pyrophosphate, and dead-end inhibition by the l-Met analog cycloleucine (l-cLeu) suggest that Mat2A follows a strictly ordered kinetic mechanism where ATP binds before l-Met and with SAM released prior to random release of phosphate and pyrophosphate. Isothermal titration calorimetry (ITC) showed binding of ATP to Mat2A with a Kd of 80 ± 30 µM, which is close to the Km(ATP) of 50 ± 10 µM. In contrast, l-Met or l-cLeu showed no binding to Mat2A in the absence of ATP; however, binding to l-cLeu was observed in the presence of ATP. The ITC results are fully consistent with the product and dead-inhibition results obtained. We also carried out kinetic studies in the presence of the physiological regulator Mat2B. Under conditions where all Mat2A is found in complex with Mat2B, no significant change in the kinetic parameters was observed despite confirmation of a very high binding affinity of Mat2A to Mat2B (Kd of 6 ± 1 nM). Finally, we found that while Mat2A is unstable at low concentrations (<100 nM), rapidly losing activity at 37 °C, it retained full activity for at least 2 h when Mat2B was present at the known 2:1 Mat2A/Mat2B stoichiometry.

A road map to structure-resistance correlations on Mycobacterium tuberculosis MmpL3.

In this issue of Structure, Adams et al. (2021) present the cryo-EM structure of Mtb MmpL3 and create a structure-based road map of resistance determinants likely to develop in response to clinical use of MmpL3 inhibitors. This structure-resistance correlation map may aid in the development of next-generation antituberculars to circumvent resistance.

Qualities of Effective Vital Anaesthesia Simulation Training Facilitators Delivering Simulation-Based Education in Resource-Limited Settings.

BACKGROUND: Lack of access to safe and affordable anesthesia and surgical care is a major contributor to avoidable death and disability across the globe. Effective education initiatives are a viable mechanism to address critical skill and process gaps in perioperative teams. Vital Anaesthesia Simulation Training (VAST) aims to overcome barriers limiting widespread application of simulation-based education (SBE) in resource-limited environments, providing immersive, low-cost, multidisciplinary SBE and simulation facilitator training. There is a dearth of knowledge regarding the factors supporting effective simulation facilitation in resource-limited environments. Frameworks evaluating simulation facilitation in high-income countries (HICs) are unlikely to fully assess the range of skills required by simulation facilitators working in resource-limited environments. This study explores the qualities of effective VAST facilitators; knowledge gained will inform the design of a framework for assessing simulation facilitators working in resource-limited contexts and promote more effective simulation faculty development. METHODS: This qualitative study used in-depth interviews to explore VAST facilitators' perspectives on attributes and practices of effective simulation in resource-limited settings. Twenty VAST facilitators were purposively sampled and consented to be interviewed. They represented 6 low- and middle-income countries (LMICs) and 3 HICs. Interviews were conducted using a semistructured interview guide. Data analysis involved open coding to inductively identify themes using labels taken from the words of study participants and those from the relevant literature. RESULTS: Emergent themes centered on 4 categories: Persona, Principles, Performance and Progression. Effective VAST facilitators embody a set of traits, style, and personal attributes (Persona) and adhere to certain Principles to optimize the simulation environment, maximize learning, and enable effective VAST Course delivery. Performance describes specific practices that well-trained facilitators demonstrate while delivering VAST courses. Finally, to advance toward competency, facilitators must seek opportunities for skill Progression.Interwoven across categories was the finding that effective VAST facilitators must be cognizant of how context, culture, and language may impact delivery of SBE. The complexity of VAST Course delivery requires that facilitators have a sensitive approach and be flexible, adaptable, and open-minded. To progress toward competency, facilitators must be open to self-reflection, be mentored, and have opportunities for practice. CONCLUSIONS: The results from this study will help to develop a simulation facilitator evaluation tool that incorporates cultural sensitivity, flexibility, and a participant-focused educational model, with broad relevance across varied resource-limited environments.

Critical structures in the needle path of the costoclavicular brachial plexus block: a cadaver study.

PURPOSE: The costoclavicular block is a relatively novel alternative to the infraclavicular block. We aimed to determine the anatomical structures vulnerable to needle injury during a costoclavicular block. METHODS: The needle path consistent with a costoclavicular block approach was performed bilaterally on four lightly embalmed cadavers using ultrasound guidance. Careful dissection was performed with 18-G Tuohy needles in situ and photographs were taken. RESULTS: The needle penetrated the deltoid in six of eight cases and the pectoralis minor in three of eight cases. The subclavius tendon or its fascia were punctured in two of eight cases. The lateral cord was in contact with the needle in six procedures and punctured in three. The posterior cord was contacted in two instances, and the medial cord in one. In a single dissection, the needle was in contact with the medial antebrachial cutaneous nerve. The needle was close to the medial brachial cutaneous nerve in one case and close to the pectoral nerves in two of eight cases. While the cephalic vein and thoracoacromial artery were consistently nearby, there were no cases of vascular puncture. CONCLUSION: We found that the needle path may be close to the medial antebrachial cutaneous nerve, medial brachial cutaneous nerve, and pectoral nerves but did not traverse any critical structures aside from the lateral cord. This suggests relative safety when compared with other approaches to the infraclavicular brachial plexus. Structures dans la trajectoire de l'aiguille du bloc de plexus brachial costoclaviculaire : une étude cadavérique.

RéSUMé: OBJECTIF: Le bloc costoclaviculaire est une alternative relativement nouvelle au bloc infraclaviculaire. Notre objectif était de déterminer quelles structures anatomiques étaient vulnérables aux lésions provoquées par l'aiguille pendant un bloc costoclaviculaire MéTHODE: Nous avons simulé, sous échoguidage, une trajectoire d'aiguille correspondant à l'approche pour un bloc costoclaviculaire en bilatéral sur quatre cadavres légèrement embaumés. Une dissection minutieuse a ensuite été exécutée avec des aiguilles Tuohy 18-G laissées in situ et des photographies ont été prises. RéSULTATS: L'aiguille a pénétré le deltoïde dans six des huit cas et le muscle petit pectoral dans trois des huit cas. Le tendon sous-clavier ou son fascia ont été perforés dans deux des huit cas. Le cordon latéral a été en contact avec l'aiguille dans six interventions et perforé dans trois cas. Le cordon postérieur a été touché dans deux cas, et le cordon médial dans un cas. L'aiguille a touché le nerf cutané antébrachial médial dans une seule dissection. L'aiguille était proche du nerf cutané brachial médial dans un cas et proche des nerfs pectoraux dans deux des huit cas. Alors que la veine céphalique et l'artère thoraco-acromiale étaient toujours à proximité, il n'y a eu aucun cas de ponction vasculaire. CONCLUSION: Nous avons constaté que la trajectoire de l'aiguille peut être à proximité du nerf cutané antébrachial médial, du nerf cutané brachial médial et du nerf pectoral, mais l'aiguille n'a pas traversé de structures critiques hormis le cordon latéral. Ceci suggère l'innocuité relative de ce type de bloc par rapport à d'autres approches du plexus brachial infraclaviculaire.

Factors associated with rebound pain after peripheral nerve block for ambulatory surgery.

BACKGROUND: Rebound pain is a common, yet under-recognised acute increase in pain severity after a peripheral nerve block (PNB) has receded, typically manifesting within 24 h after the block was performed. This retrospective cohort study investigated the incidence and factors associated with rebound pain in patients who received a PNB for ambulatory surgery. METHODS: Ambulatory surgery patients who received a preoperative PNB between March 2017 and February 2019 were included. Rebound pain was defined as the transition from well-controlled pain (numerical rating scale [NRS] ≤3) while the block is working to severe pain (NRS ≥7) within 24 h of block performance. Patient, surgical, and anaesthetic factors were analysed for association with rebound pain by univariate, multivariable, and machine learning methods. RESULTS: Four hundred and eighty-two (49.6%) of 972 included patients experienced rebound pain as per the definition. Multivariable analysis showed that the factors independently associated with rebound pain were younger age (odds ratio [OR] 0.98; 95% confidence interval [CI] 0.97-0.99), female gender (OR 1.52 [1.15-2.02]), surgery involving bone (OR 1.82 [1.38-2.40]), and absence of perioperative i.v. dexamethasone (OR 1.78 [1.12-2.83]). Despite a high incidence of rebound pain, there were high rates of patient satisfaction (83.2%) and return to daily activities (96.5%). CONCLUSIONS: Rebound pain occurred in half of the patients and showed independent associations with age, female gender, bone surgery, and absence of intraoperative use of i.v. dexamethasone. Until further research is available, clinicians should continue to use preventative strategies, especially for patients at higher risk of experiencing rebound pain.