Feasibility pilot trial for the Trajectories of Recovery after Intravenous propofol versus inhaled VolatilE anesthesia (THRIVE) pragmatic randomised controlled trial

INTRODUCTION: Millions of patients receive general anaesthesia for surgery annually. Crucial gaps in evidence exist regarding which technique, propofol total intravenous anaesthesia (TIVA) or inhaled volatile anaesthesia (INVA), yields superior patient experience, safety and outcomes. The aim of this pilot study is to assess the feasibility of conducting a large comparative effectiveness trial assessing patient experiences and outcomes after receiving propofol TIVA or INVA. METHODS AND ANALYSIS: This protocol was cocreated by a diverse team, including patient partners with personal experience of TIVA or INVA. The design is a 300-patient, two-centre, randomised, feasibility pilot trial. Patients 18 years of age or older, undergoing elective non-cardiac surgery requiring general anaesthesia with a tracheal tube or laryngeal mask airway will be eligible. Patients will be randomised 1:1 to propofol TIVA or INVA, stratified by centre and procedural complexity. The feasibility endpoints include: (1) proportion of patients approached who agree to participate; (2) proportion of patients who receive their assigned randomised treatment; (3) completeness of outcomes data collection and (4) feasibility of data management procedures. Proportions and 95% CIs will be calculated to assess whether prespecified thresholds are met for the feasibility parameters. If the lower bounds of the 95% CI are above the thresholds of 10% for the proportion of patients agreeing to participate among those approached and 80% for compliance with treatment allocation for each randomised treatment group, this will suggest that our planned pragmatic 12 500-patient comparative effectiveness trial can likely be conducted successfully. Other feasibility outcomes and adverse events will be described. ETHICS AND DISSEMINATION: This study is approved by the ethics board at Washington University (IRB# 202205053), serving as the single Institutional Review Board for both participating sites. Recruitment began in September 2022. Dissemination plans include presentations at scientific conferences, scientific publications, internet-based educational materials and mass media. TRIAL REGISTRATION NUMBER: NCT05346588

Serratia marcescens internalization and replication in human bladder epithelial cells

BACKGROUND: Serratia marcescens, a frequent agent of catheterization-associated bacteriuria, strongly adheres to human bladder epithelial cells in culture. The epithelium normally provides a barrier between lumal organisms and the interstitium; the tight adhesion of bacteria to the epithelial cells can lead to internalization and subsequent lysis. However, internalisation was not shown yet for S. marcescens strains. METHODS: Elektronmicroscopy and the common gentamycin protection assay was used to assess intracellular bacteria. Via site directed mutagenesis, an hemolytic negative isogenic Serratia strain was generated to point out the importance of hemolysin production. RESULTS: We identified an important bacterial factor mediating the internalization of S. marcescens, and lysis of epithelial cells, as the secreted cytolysin ShlA. Microtubule filaments and actin filaments were shown to be involved in internalization. However, cytolysis of eukaryotic cells by ShlA was an interfering factor, and therefore hemolytic-negative mutants were used in subsequent experiments. Isogenic hemolysin-negative mutant strains were still adhesive, but were no longer cytotoxic, did not disrupt the cell culture monolayer, and were no longer internalized by HEp-2 and RT112 bladder epithelial cells under the conditions used for the wild-type strain. After wild-type S. marcescens became intracellular, the infected epithelial cells were lysed by extended vacuolation induced by ShlA. In late stages of vacuolation, highly motile S. marcescens cells were observed in the vacuoles. S. marcescens was also able to replicate in cultured HEp-2 cells, and replication was not dependent on hemolysin production. CONCLUSION: The results reported here showed that the pore-forming toxin ShlA triggers microtubule-dependent invasion and is the main factor inducing lysis of the epithelial cells to release the bacteria, and therefore plays a major role in the development of S. marcescens infections

Healthcare Access as a Risk-Marker for Obstetric Vesicovaginal Fistula in Malawi

Objectives: To determine the association between access to health care among pregnant women in Malawi and occurrence of obstetric vesicovaginal fistula (VVF). Methods: This was a case-control study using data obtained from patients’ records documented by the ‘Fistula Care Center-Bwaila Hospital’ in Malawi. Socio-demographic characteristics of women with VVF (study arm, n=1046) and perineal tear (control arm, n=37) were examined. A composite variable called “Malawi Healthcare Access Index” (MHAI) was created through summation of scores related to three factors of access to care: (1) walking distance to closest health center; (2) presence of trained provider at delivery; and (3) receipt of antenatal care. Binomial logistic regression models were built to determine the association between the MHAI and presence of VVF. Results: Obstetric VVF was more common in women from rural areas, mothers delivering at extremes of age, those with less education, and patients with long labor (>12 hours). In adjusted models, women with “insufficient” health access based on the MHAI were at greater risk (OR = 2.64, 95%CI = 1.07 – 6.03) of obstetric VVF than women with “sufficient” score on the MHAI. Conclusion and Global Health Implications: Inadequate access to essential obstetric care increases the risk of VVF. Key words: • Health care index • Obstetric complications • Vesicovaginal fistula • Poverty • Malawi • Malawi Healthcare Access Index   Copyright © 2020 Rupley et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Perineural dexmedetomidine added to ropivacaine causes a dose-dependent increase in the duration of thermal antinociception in sciatic nerve block in rat. Anesthesiology 2009

ABSTRACT Background: The current study was designed to test the hypothesis that the increased duration of analgesia caused by adding dexmedetomidine to local anesthetic results from blockade of the hyperpolarization-activated cation (I h ) current. Methods: In this randomized, blinded, controlled study, the analgesic effects of peripheral nerve blocks using 0.5% ropivacaine alone or 0.5% ropivacaine plus dexmedetomidine (34 M or 6 g/kg) were assessed with or without the pretreatment of ␣ 1 -and ␣ 2 -adrenoceptor antagonists (prazosin and idazoxan, respectively) and antagonists and agonists o

Brome Mosaic Virus Protein 1a Recruits Viral RNA2 to RNA Replication through a 5′ Proximal RNA2 Signal

Brome mosaic virus (BMV), a positive-strand RNA virus in the alphavirus-like superfamily, encodes two RNA replication factors. Membrane-associated 1a protein contains a helicase-like domain and RNA capping functions. 2a, which is targeted to membranes by 1a, contains a central polymerase-like domain. In the absence of 2a and RNA replication, 1a acts through an intergenic replication signal in BMV genomic RNA3 to stabilize RNA3 and induce RNA3 to associate with cellular membrane. Multiple results imply that 1a-induced RNA3 stabilization reflects interactions involved in recruiting RNA3 templates into replication. To determine if 1a had similar effects on another BMV RNA replication template, we constructed a plasmid expressing BMV genomic RNA2 in vivo. In vivo-expressed RNA2 templates were replicated upon expression of 1a and 2a. In the absence of 2a, 1a stabilized RNA2 and induced RNA2 to associate with membrane. Deletion analysis demonstrated that 1a-induced membrane association of RNA2 was mediated by sequences in the 5′-proximal third of RNA2. The RNA2 5′ untranslated region was sufficient to confer 1a-induced membrane association on a nonviral RNA. However, sequences in the N-terminal region of the 2a open reading frame enhanced 1a responsiveness of RNA2 and a chimeric RNA. A 5′-terminal RNA2 stem-loop important for RNA2 replication was essential for 1a-induced membrane association of RNA2 and, like the 1a-responsive RNA3 intergenic region, contained a required box B motif corresponding to the TΨC stem-loop of host tRNAs. The level of 1a-induced membrane association of various RNA2 mutants correlated well with their abilities to serve as replication templates. These results support and expand the conclusion that 1a-induced BMV RNA stabilization and membrane association reflect early, 1a-mediated steps in viral RNA replication

A survey of surgical patients’ perspectives and preferences towards general anesthesia techniques and shared-decision making

Abstract Background The decision about which type of general anesthetic to administer is typically made by the clinical team without patient engagement. This study examined patients’ preferences, experiences, attitudes, beliefs, perceptions, and perceived social norms about anesthesia and about engaging in the decision regarding general anesthetic choice with their clinician. Methods We conducted a survey in the United States, sent to a panel of surgical patients through Qualtrics (Qualtrics, Provo, UT) from March 2022 through May 2022. Questions were developed based on the Theory of Planned Behavior and validated measures were used when available. A patient partner who had experienced both intravenous and inhaled anesthesia contributed to the development and refinement of the questions. Results A total of 806 patients who received general anesthesia for an elective procedure in the last five years completed the survey. 43% of respondents preferred a patient-led decision making role and 28% preferred to share decision making with their clinical team, yet only 7.8% reported being engaged in full shared decision making about the anesthesia they received. Intraoperative awareness, pain, nausea, vomiting and quickly returning to work and usual household activities were important to respondents. Waking up in the middle of surgery was the most commonly reported concern, despite this experience being reported only 8% of the time. Most patients (65%) who searched for information about general anesthesia noted that it took a lot of effort to find the information, and 53% agreed to feeling frustrated during the search. Conclusions Most patients prefer a patient-led or shared decision making process when it comes to their anesthetic care and want to be engaged in the decision. However, only a small percentage of patients reported being fully engaged in the decision. Further studies should inform future shared decision-making tools, informed consent materials, educational materials and framing of anesthetic choices for patients so that they are able to make a choice regarding the anesthetic they receive