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.

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.

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.

Continuous peripheral nerve blocks compared to thoracic epidurals or multimodal analgesia for midline laparotomy: a systematic review and meta-analysis.

BACKGROUND: Continuous peripheral nerve blocks (CPNBs) have been investigated to control pain for abdominal surgery via midline laparotomy while avoiding the adverse events of opioid or epidural analgesia. The review compiles the evidence comparing CPNBs to multimodal and epidural analgesia. METHODS: We conducted a systematic review using broad search terms in MEDLINE, EMBASE, Cochrane. Primary outcomes were pain scores and cumulative opioid consumption at 48 hours. Secondary outcomes were length of stay and postoperative nausea and vomiting (PONV). We rated the quality of the evidence using Cochrane and GRADE recommendations. The results were synthesized by meta-analysis using Revman. RESULTS: Our final selection included 26 studies (1,646 patients). There was no statistically significant difference in pain control comparing CPNBs to either multimodal or epidural analgesia (low quality evidence). Less opioids were consumed when receiving epidural analgesia than CPNBs (mean difference [MD]: -16.13, 95% CI [-32.36, 0.10]), low quality evidence) and less when receiving CPNBs than multimodal analgesia (MD: -31.52, 95% CI [-42.81, -20.22], low quality evidence). The length of hospital stay was shorter when receiving epidural analgesia than CPNBs (MD: -0.78 days, 95% CI [-1.29, -0.27], low quality evidence) and shorter when receiving CPNBs than multimodal analgesia (MD: -1.41 days, 95% CI [-2.45, -0.36], low quality evidence). There was no statistically significant difference in PONV comparing CPNBs to multimodal (high quality evidence) or epidural analgesia (moderate quality evidence). CONCLUSIONS: CPNBs should be considered a viable alternative to epidural analgesia when contraindications to epidural placement exist for patients undergoing midline laparotomies.

Persistence of the antimicrobials lincomycin, chlortetracycline, and sulfamethazine in prairie wetlands.

Antimicrobials used in livestock production can be present in manure via excretion in the feces and/or urine. Application of raw or processed (composted or stockpiled) manure to crop and pasture land as a plant nutrient source can result in antimicrobial transport to surface waters via rainfall or snowmelt runoff. Little is known regarding antimicrobial persistence in aquatic ecosystems. Consequently, dissipation of environmentally relevant concentrations of three veterinary antimicrobials (lincomycin, chlortetracycline, and sulfamethazine) was studied in three wetlands on the Canadian Prairies. Study wetlands were fortified in the fall to simulate antimicrobial transport via rainfall runoff from fall manure applications to the wetland catchments. After fortification, water column concentrations of all three antimicrobials decreased through September and October. Plotting natural logarithm values of antimicrobial concentration against time resulted in linear relationships for all three antimicrobials, indicating that the summation of all dissipation processes for each antimicrobial could be described by first-order kinetics. The slopes of the three plots were significantly different, indicating that the order of dissipation was lincomycin < sulfamethazine < chlortetracycline. Consequently, the dissipation DT50 (time required for 50% antimicrobial dissipation) values for lincomycin (14.0 d), sulfamethazine (7.0 d), and chlortetracycline (3.3 d) were significantly different. The longer DT50 values of lincomycin and sulfamethazine suggest that environmentally relevant concentrations of these antimicrobials may affect bacterial production in prairie wetlands.

Isomerization of chlortetracycline in prairie wetland water.

Chlortetracycline (CTC), an antimicrobial administered as a feed additive to cattle, swine, and poultry, is present in the corresponding manure. Land application of raw or processed (composted or stockpiled) manure provides a mechanism by which CTC (and other antimicrobials) enters the environment and becomes available for transport to surface receiving waters via rainfall or snowmelt runoff. Chlortetracycline has been detected in Canadian surface waters, but little has been reported on its fate in aquatic ecosystems. To address this knowledge gap, the dissipation of CTC-enol was monitored in deionized water and water typical of wetlands within the prairie region of Canada. In deionized water, CTC-enol tautomerized to CTC-keto, and both tautomers epimerized to 4-epi-CTC-enol and 4-epi-CTC-keto, respectively. Irreversible isomerization to iso-CTC occurred, which then epimerized to 4-epi-iso-CTC. In wetland water, although tauterization of CTC-enol to CTC-keto occurred, there was no evidence of the formation of the 4-epimers of either CTC-enol or CTC-keto. The major product formed in the wetland water was iso-CTC, some of which epimerized to 4-epi-iso-CTC. Although CTC-enol was shown to tautomerize to CTC-keto, the concentration of CTC-keto remained low in both deionized and wetland water, suggesting that the isomerization of CTC-enol to iso-CTC most likely occurred via CTC-keto. The dissipation of CTC-enol in wetland water was described by pseudo first-order kinetics with a DT50 (time required for 50% dissipation) value of 4.8 h. The short DT50 value of CTC and reduced antimicrobial activity of iso-CTC and 4-epi-iso-CTC suggest a lower probability for selection for CTC-resistant bacteria in Canadian Prairie aquatic ecosystems.