Κυριακή 27 Δεκεμβρίου 2020

Barrier Devices, Intubation, and Aerosol Mitigation Strategies: Personal Protective Equipment in the Time of Coronavirus Disease 2019

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imageBackground: Numerous barrier devices have recently been developed and rapidly deployed worldwide in an effort to protect health care workers (HCWs) from exposure to coronavirus disease 2019 (COVID-19) during high-risk procedures. However, only a few studies have examined their impact on the dispersion of droplets and aerosols, which are both thought to be significant contributors to the spread of COVID-19. METHODS: Two commonly used barrier devices, an intubation box and a clear plastic intubation sheet, were evaluated using a physiologically accurate cough simulator. Aerosols were modeled using a commercially available fog machine, and droplets were modeled with fluorescein dye. Both particles were propelled by the cough simulator in a simulated intubation environment. Data were captured by high-speed flash photography, and aerosol and droplet dispersion were assessed qualitatively with and without a barrier in place. RESULTS: Droplet contamination after a simulated cough was seemingly contained by both barrier devices. Simulated aerosol escaped the barriers and flowed toward the head of the bed. During barrier removal, simulated aerosol trapped underneath was released and propelled toward the HCW at the head of the bed. Usage of the intubation sheet concentrated droplets onto a smaller area. If no barrier was used, positioning the patient in slight reverse Trendelenburg directed aerosols away from the HCW located at the head of the bed. CONCLUSIONS: Our observations imply that intubation boxes and sheets may reduce HCW exposure to droplets, but they both may merely redirect aerosolized particles, potentially resulting in increased exposure to aerosols in certain circumstances. Aerosols may remain within the barrier device after a cough, and manipulation of the box may release them. Patients should be positioned to facilitate intubation, but slight reverse Trendelenburg may direct infectious aerosols away from the HCW. Novel barrier devices should be used with caution, and further validation studies are necessary.
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Adaptation of an Obstetric Anesthesia Service for the Severe Acute Respiratory Syndrome Coronavirus-2 Pandemic: Description of Checklists, Workflows, and Development Tools

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imageBackground: Care of the pregnant patient during the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic presents many challenges, including creating parallel workflows for infected and noninfected patients, minimizing waste of materials, and ensuring that clinicians can seamlessly transition between types of anesthesia. The exponential community spread of disease limited the time for development and training. METHODS: The goals of our workflow and process development were to maximize safety for staff and patients, minimize the risk of contamination, and reduce the waste of unused supplies and materials. We used a cyclical improvement system and the plus/delta debriefing method to rapidly develop workflows consisting of sequential checklists and procedure-specific packs. RESULTS: We designed independent workflows for labor analgesia, neuraxial anesthesia for cesarean delivery, conversion of labor analgesia to cesarean anesthesia, and general anesthesia. In addition, we created procedure-specific material packs to optimize supplies and prevent wastage. Finally, we generated sequential checklists to allow staff to perform standard operating procedures without extensive training. CONCLUSIONS: Collectively, these workflows and tools allowed our staff to urgently care for patients in high-risk situations without prior experience. Over time, we refined the workflows using a cyclical improvement system. We present our checklists and workflows as well as the system we used for their development, so that others may use them to their benefit.
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The Clinical Use of Cricoid Pressure: First, Do No Harm

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imageApplication of cricoid pressure (CP) during rapid sequence induction and intubation sequence has been a "standard" of care for many decades, despite limited scientific proof of its efficacy in preventing pulmonary aspiration of gastric contents. While some of the current rapid sequence induction and intubation guidelines recommend its use, other international guidelines do not, and many clinicians argue that there is insufficient evidence to either continue or abandon its use. Recently published articles and accompanying editorials have reignited the debate on the efficacy and safety of CP application and have generated multiple responses that pointed out the various (and significant) limitations of the available evidence. Thus, a critical discussion of available data must be undertaken before making a final clinical decision on such an important patient safety issue. In this review, the authors will take an objective look at the available scientific evidence about the effectiveness and safety of CP in patients at risk of pulmonary aspiration of gastric contents. We suggest that current data are inadequate to impose clinical guidelines on the use of CP because we acknowledge that currently there is not, and there may never be, a method to prevent aspiration in all patients. In addition, we reiterate that a universally accepted medical-legal standard for approaching the high-risk aspiration patient does not exist, discuss the differences in practice between the US and international practitioners regarding use of CP, and propose 5 recommendations on how future studies might be designed to obtain optimal scientific evidence about the effectiveness and safety of CP in patients at risk for pulmonary aspiration.
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Effectiveness of Prone Positioning in Nonintubated Intensive Care Unit Patients With Moderate to Severe Acute Respiratory Distress Syndrome by Coronavirus Disease 2019

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imageBackground: In the treatment for severe acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19), the World Health Organization (WHO) recommends prone positioning (PP) during mechanical ventilation for periods of 12–16 h/d to potentially improve oxygenation and survival. In this prospective observational study, we evaluated the ability of long PP sessions to improve oxygenation in awake intensive care unit (ICU) patients with moderate or severe ARDS due to COVID-19. METHODS: The study was approved by the ethics committee of Galicia (code No. 2020-188), and all patients provided informed consent. In this case series, awake patients with moderate or severe ARDS by COVID-19 admitted to the ICU at University Hospital of Santiago from March 21 to April 5, 2020 were prospectively analyzed. Patients were instructed to remain in PP as long as possible until the patient felt too tired to maintain that position. Light sedation was administered with dexmedetomidine. The following information was collected: number and duration of PP sessions; tissue O2 saturation (Sto2) and blood gases before, during, and following a PP session; need of mechanical ventilation; duration of ICU admission; and ICU outcome. Linear mixed-effects models (LMM) were fit to estimate changes from baseline with a random effect for patient. RESULTS: Seven patients with moderate or severe ARDS by COVID-19 were included. All patients received at least 1 PP session. A total of 16 PP sessions were performed in the 7 patients during the period study. The median duration of PP sessions was 10 hours. Dexmedetomidine was used in all PP sessions. Oxygenation increased in all 16 sessions performed in the 7 patients. The ratio of arterial oxygen partial pressure to fractional inspired oxygen (Pao2/Fio2) significantly increased during PP (change from baseline 110 with 97.5% confidence interval [CI], 19-202) and, after PP, albeit not significantly (change from baseline 38 with 97.5% CI, −9.2 to 85) compared with previous supine position. Similarly, tissue oxygenation underwent a small improvement during PP (change from baseline 2.6% with 97.5% CI, 0.69-4.6) without significant changes after PP. Two patients required intubation. All patients were discharged from the ICU. CONCLUSIONS: We found that PP improved oxygenation in ICU patients with COVID-19 and moderate or severe ARDS. PP was relatively well tolerated in our patients and may be a simple strategy to improve oxygenation trying to reduce the number of patients in mechanical ventilation and the length of stay in the ICU, especially in COVID-19 pandemic.
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The Current State of Combined Pediatric Anesthesiology–Critical Care Practice: A Survey of Dual-Trained Practitioners in the United States

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imageBackground: Combined practice in pediatric anesthesiology (PA) and pediatric critical care medicine (PCCM) was historically common but has declined markedly with time. The reasons for this temporal shift are unclear, but existing evidence suggests that length of training is a barrier to contemporary trainees. Among current practitioners, restriction in dual-specialty practice also occurs, for reasons that are unknown at present. We sought to describe the demographics of this population, investigate their perceptions about the field, and consider factors that lead to attrition. METHODS: We conducted a cross-sectional, observational study of physicians in the United States with a combined practice in PA and PCCM. The survey was distributed electronically and anonymously to the distribution list of the Pediatric Anesthesia Leadership Council (PALC) of the Society for Pediatric Anesthesia (SPA), directing the recipients to forward the link to their faculty meeting our inclusion criteria. Attending-level respondents (n = 62) completed an anonymous, 40-question multidomain survey. RESULTS: Forty-seven men and 15 women, with a median age of 51, completed the survey. Major leadership positions are held by 44%, and 55% are externally funded investigators. A minority (26%) have given up one or both specialties, citing time constraints and politics as the dominant reasons. Duration of training was cited as the major barrier to entry by 77%. Increasing age and faculty rank and lack of a comparably trained institutional colleague were associated with attrition from dual-specialty practice. The majority (88%) reported that they would do it all again. CONCLUSIONS: The current cohort of pediatric anesthesiologist–intensivists in the United States is a small but accomplished group of physicians. Efforts to train, recruit, and retain such providers must address systematic barriers to completion of the requisite training and continued practice.
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A Developing Nation’s Experience in Using Simulation-Based Training as a Preparation Tool for the Coronavirus Disease 2019 Outbreak

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imageBackground: The coronavirus disease 2019 (COVID-19) pandemic affected and overwhelmed many health care systems around the world at an unprecedented speed and magnitude with devastating effects. In developing nations, smaller hospitals were unprepared to face this outbreak nor had strategies in place to do so at the beginning. Here, we describe the preparation in an anesthetic department using simulation-based training over 2 weeks, as the number of cases rose rapidly. METHODS: Three areas of priority were identified as follows: staff safety, patient movement, and possible clinical scenarios based on simulation principles in health care education. Staff was rostered and rotated through stations for rapid-cycle deliberate practice to learn donning and doffing of personal protective equipment (PPE) and powered air-purifying respirator (PAPR). For difficult airway management, Peyton's 4 steps for skills training and Harden's Three Circle model formed the structure in teaching the core skills. Several clinical scenarios used system probing to elicit inadequacies followed by formal debriefing to facilitate reflection. Finally, evaluation was both immediate and delayed with an online survey after 1 month to examine 4 levels of reaction, learning, behavior, and impact based on the Kirkpatrick Model. Frequency and thematic analysis were then conducted on the quantitative and qualitative data, respectively. RESULTS: A total of 15 of 16 (93%) consultants, 16 (100%) specialists, and 81 (100%) medical officers in the department completed training within 2 consecutive weeks. Reaction and part of the learning were relayed immediately to trainers during training. In total, 42 (39%) trained staff responded to the survey. All were satisfied and agreed on the relevance of training. A total of 41 respondents (98%; 95% confidence interval [CI], 87-99) answered 16 of 20 questions correctly on identifying aerosol-generating procedures (AGP), indications for PPE, planning and preparation for airway management to achieve adequate learning. About 43% (95% CI, 27-59) and 52% (95% CI, 36-68) recalled donning and doffing steps correctly. A total of 92 responses from 33 respondents were analyzed in the thematic analysis. All respondents reported at least 1 behavioral change in intended outcomes for hand hygiene practice (20%), appropriate use of PPE (27%), and airway management (10%). The emerging outcomes were vig ilance, physical distancing, planning, and team communication. Finally, the impact of training led to the establishment of institutional guidelines followed by all personnel. CONCLUSIONS: Simulation-based training was a useful preparation tool for small institutions with limited time, resources, and manpower in developing nations. These recommendations represent the training experience to address issues of "when" and "how" to initiate urgent "medical education" during an outbreak.
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Decontamination and Reuse of N95 Filtering Facepiece Respirators: Where Do We Stand?

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imageThe coronavirus disease 2019 (COVID-19) pandemic created an extraordinary demand for N95 and similarly rated filtering facepiece respirators (FFR) that remains unmet due to limited stock, production constraints, and logistics. Interest in decontamination and reuse of FFR, a product class designed for single use in health care settings, has undergone a parallel surge due to shortages. A worthwhile decontamination method must provide effective inactivation of the targeted pathogen(s), and preserve particle filtration, mask fit, and safety for a subsequent user. This discussion reviews the background of t he current shortage, classification, structure, and functional aspects of FFR, and potentially effective decontamination methods along with reference websites for those seeking updated information and guidance. The most promising techniques utilize heat, hydrogen peroxide, microwave-generated steam, or ultraviolet light. Many require special or repurposed equipment and a detailed operational roadmap specific to each setting. While limited, research is growing. There is significant variation between models with regard to the ability to withstand decontamination yet remain protective. The number of times an individual respirator can be reused is often limited by its ability to maintain a tight fit after multiple uses rather than by the decontamination method itself. There is no single solution for all settings; each individual or institution must choose according to their need, capability, and available resources. As the current pandemic is expected to continue for months to years, an d the possibility of future airborne biologic threats persists, the need for plentiful, effective respiratory protection is stimulating research and innovation.
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Treating patients across European Union borders: An international survey in light of the coronavirus disease-19 pandemic

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BACKGROUND In light of the coronavirus disease-2019 (COVID-19) pandemic, how resources are managed and the critically ill are allocated must be reviewed. Although ethical recommendations have been published, strategies for dealing with overcapacity of critical care resources have so far not been addressed. OBJECTIVES Assess expert opinion for allocation preferences regarding the growing imbalance between supply and demand for medical resources. DESIGN A 10-item questionnaire was developed and sent to the most prominent members of the European Society of Anaesthesiology and Intensive Care (ESAIC). SETTING Survey via a web-based platform. PATIENTS Respondents were members of the National Anaesthesiologists Societies Committee and Council Members of the ESAIC; 74 of 80 (92.5%), responded to the survey. MEASUREMENTS AND MAIN RESULTS Responses were analysed thematically. The majority of respondents (83.8%), indicated that resources for COVID-19 were available at the time of the survey. Of the representatives of the ESAIC governing bodies, 58.9% favoured an allocation of excess critical care capacity: 69% wished to make them available to supraregional patients, whereas 30.9% preferred to keep the resources available for the local population. Regarding the type of distribution of resources, 35.3% preferred to make critical care available, 32.4% favoured the allocation of medical equipment and 32.4% wished to support both options. The majority (59.5%) supported the implementation of a central European institution to manage such resource allocation. CONCLUSION Experts in critical care support the allocation of resources from centres with overcapacity. The results indicate the need for centrally administered allocation mechanisms that are not based on ethically disputable triage systems. It seems, therefore, that there is wide acceptance and solidarity among the European anaesthesiological community that local medical and human pressure should be relieved during a pandemic by implementing national and international re-allocation strategies among healthcare providers and healthcare systems. Correspondence to Elisabeth H. Adam, MD, MHBA, Department of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern Kai 7, 60590 Frankfurt, Germany Tel: +49 69 6301 5868; fax: +49 69 6301 7695; e-mail: elisabeth.adam@kgu.de Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.ejanaesthesiology.com). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 © 2020 European Society of Anaesthesiology
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Isthmin1, a secreted signaling protein, acts downstream of diverse embryonic patterning centers in development

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Abstract

Extracellular signals play essential roles during embryonic patterning by providing positional information in a concentration-dependent manner, and many such signals, like Wnt, fibroblast growth factor (FGF), Hedgehog (Hh), and retinoic acid, act by being secreted into the extracellular space, thereby triggering receptor-mediated responses in other cells. Isthmin1 (ism1) is a secreted protein whose gene expression pattern coincides with that of early dorsal determinants, nodal ligand genes like sqt and cyc, and with fgf8 during various phases of zebrafish development. Ism1 functions in early embryonic patterning and development are poorly understood; however, it has recently been shown to interact with nodal pathway genes to control organ asymmetry in chicken. Here, we show that misexpression of ism1 deletion constructs disrupts embryonic patterning in zebrafish and exhibits genetic interactions with both Fgf and nodal signaling. Unlike Fgf and nodal pathway mutants, CRISPR/Cas9-engineered ism1 mutants did not show obvious developmental defects. Further, in vivo single molecule fluorescence correlation spectroscopy (FCCS) showed that Ism1 diffuses freely in the extra-cellular space, with a diffusion coefficient similar to that of Fgf8a; however, our measurements do not support direct molecular interactions between Ism1 and either nodal ligands or Fgf8a in the developing zebrafish embryo. Together, data from gain- and loss-of-function experiments suggest that zebrafish Ism1 plays a complex role in regulating extracellular signals during early embryonic development.

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Cancers, Vol. 13, Pages 54: Targeting the Roots of Recurrence: New Strategies for Eliminating Therapy-Resistant Breast Cancer Stem Cells

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Cancers, Vol. 13, Pages 54: Targeting the Roots of Recurrence: New Strategies for Eliminating Therapy-Resistant Breast Cancer Stem Cells

Cancers doi: 10.3390/cancers13010054

Authors: Margaret L. Dahn Paola Marcato

Cancer stem cells (CSCs) are functionally defined in our laboratories by their impressive tumor-generating and self-renewal capacity; clinically, CSCs are of interest because of their enhanced capacity to evade conventional therapies [...]

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Correlation Between Invasive and Noninvasive Technique of Intracranial Pressure Measurement in Children With Traumatic Brain Injury: An Observational Study

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Background: Direct measurement of intracranial pressure (ICP) is an invasive technique with potential complications, which has prompted the development of alternative, noninvasive, methods of ICP assessment. The aim of this study was to determine the relationship between noninvasive ultrasound-based measurement of optic nerve sheath diameter (ONSD), transcranial Doppler-derived pulsatility index (PI), and invasive ICP measurements in children with traumatic brain injury (TBI). Methods: Children aged 1 to 18 years undergoing invasive ICP monitoring following TBI were included in the study. Noninvasive ONSD and PI measurements were compared with simultaneous invasive ICP. Results: In all, 406 measurements of ONSD and PI were obtained in 18 patients. ONSD and PI correlated with ICP (r=0.76 and 0.79, respectively), combining ONSD and PI resulted in an even stronger correlation with ICP (r=0.99). Formulas were derived from mixed-effect models that best fitted the data for noninvasive ICP estimation. A combination of ONSD and PI had the highest ability to detect ICP >20 mm Hg (area under the receiver operating characteristic curve=0.99, 95% confidence interval: 0.99-1.00). Optimal cutoff values for the prediction of intracranial hypertension were 5.95 mm for ONSD (sensitivity, 92%; specificity, 76%) and 1.065 for PI (sensitivity, 92%; specificity, 87%). Conclusions: In children with TBI, a combination of ONSD and PI strongly correlates with invasive ICP and has potential to screen for intracranial hypertension noninvasively. ONSD and PI may be useful tools for assessing ICP where invasive monitoring is unavailable or contraindicated. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Gyaninder P. Singh, DM. E-mail: drsingh_gp@yahoo.co.in. Received August 2, 2020 Accepted November 20, 2020 Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved
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