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Background and aim: The COVID-19 pandemic has led to a proliferation of intubation barriers designed to protect healthcare workers from infection. We developed the Suction-Assisted Local Aerosol Containment Chamber (SLACC) and tested it in the operating room. The primary objectives were to determine the ease and safety of airway management with SLACC, and to measure its efficacy of aerosol containment to determine if it significantly reduces exposure to health care workers. Methods: In this randomized clinical trial, adult patients scheduled to undergo elective surgery with general endotracheal anesthesia were screened and informed consent obtained from those willing to participate. Patients were randomized to airway management either with or without the SLACC device. Patients inhaled nebulized saline before and during anesthesia induction to simulate the size and concentration of particles seen with severe symptomatic SARS-CoV-2 infection. Results: 79 patients were enrolled and randomized. Particle number concentration (PNC) at the patients' and healthcare workers' locations were measured and compared between the SLACC vs. control groups during airway management. Ease and success of tracheal intubation were recorded for each patient. All intubations were successful and time to intubation was similar between the two groups. Healthcare workers were exposed to significantly lower particle number concentrations (#/cm3) during airway management when SLACC was utilized vs. control. The particle count outside SLACC was reduced by 97% compared to that inside the device. Conclusions: The SLACC device does not interfere with airway management and significantly reduces healthcare worker exposure to aerosolized particles during airway management.
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Glucocorticoids (GCs) are excellent anti-inflammatory drugs but are dose-limited by on-target toxicity. We sought to solve this problem by delivering GCs to immune cells with antibody-drug conjugates (ADCs) using antibodies containing site-specific incorporation of a non-natural amino acid, novel linker chemistry for in vitro and in vivo stability, and existing and novel glucocorticoid receptor (GR) agonists as payloads. We directed fluticasone propionate to human antigen-presenting immune cells to afford GR activation that was dependent on the targeted antigen. However, mechanism of action studies pointed to accumulation of free payload in the tissue culture supernatant as the dominant driver of activity and indeed administration of the ADC to human CD74 transgenic mice failed to activate GR target genes in splenic B cells. Suspecting dissipation of released payload, we designed an ADC bearing a novel GR agonist payload with reduced permeability which afforded cell-intrinsic activity in human B cells. Our work shows that antibody-targeting offers significant potential for rescuing existing and new dose-limited drugs outside the field of oncology.
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Anticorpos Monoclonais/uso terapêutico , Antígenos de Diferenciação de Linfócitos B/imunologia , Linfócitos B/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Glucocorticoides/administração & dosagem , Antígenos de Histocompatibilidade Classe II/imunologia , Imunoconjugados/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Linfócitos B/efeitos dos fármacos , Desenvolvimento de Medicamentos , Estabilidade de Medicamentos , Fluticasona/administração & dosagem , Humanos , Camundongos , Camundongos Transgênicos , Receptores de Glucocorticoides/agonistasRESUMO
BACKGROUND: Endotracheal tube security is a critical safety issue. We compared the mobility of an in situ endotracheal tube secured with adhesive tape to the one secured with a new commercially available purpose-designed endotracheal tube-holder device (Haider Tube-Guard). We also observed for the incidence of oropharyngeal or facial trauma associated with the 2 tube fixation methods. METHODS: Thirty adult patients undergoing general anesthesia with neuromuscular blockade were prospectively enrolled. Immediately after intubation, a single study author positioned the endotracheal tube tip in the distal trachea using a bronchoscope. Anesthesiologists caring for patients secured the tube in their normal fashion (always with adhesive tape). A force transducer was used to apply linear force, increasing to 15 N or until the principal investigator deemed that the force be aborted for safety reasons. The displacement of the endotracheal tube was measured with the bronchoscope. Any tape was then removed and the endotracheal tube secured with the Haider Tube-Guard device. The linear force was reapplied and the displacement of the endotracheal tube measured. The Haider Tube-Guard device was left in place for the duration of the case. The patient's face and oropharynx were examined for any evidence of trauma during surgery and in the recovery room. On discharge from the postanesthesia care unit, the patient answered a brief survey assessing for any subjective evidence of minor facial or oropharyngeal trauma. RESULTS: Under standardized tension, the endotracheal tube withdrew a mean distance of 3.4 cm when secured with adhesive tape versus 0.3 cm when secured with the Haider Tube-Guard (P <0.001). Ninety-seven percent of patients (29/30) experienced clinically significant endotracheal tube movement (>1 cm) when adhesive tape was used to secure the tube versus 3% (1/30) when the Haider Tube-Guard was used (P <0.001). Thirty percent of patients (9/30) were potentially deemed a high extubation risk (endotracheal tube movement >4 cm) when the endotracheal tube was secured with tape versus 0% (0/30) when secured with the Haider Tube-Guard (P = 0.004). Six patients with taped endotracheal tubes required the traction to be aborted before 15 N of force was achieved to prevent potential extubation as the tape either separated from the face or stretched to allow excessive endotracheal tube movement. None of the patients appeared to sustain any injury from the Haider Tube-Guard device. CONCLUSIONS: The Haider Tube-Guard significantly reduced the mobility of the endotracheal tube when compared with adhesive tape and was well tolerated in our observations.
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Extubação , Tubos Torácicos , Migração de Corpo Estranho/prevenção & controle , Intubação Intratraqueal/instrumentação , Fita Cirúrgica , Anestesia Geral , Broncoscopia , Desenho de Equipamento , Traumatismos Faciais/etiologia , Migração de Corpo Estranho/etiologia , Humanos , Intubação Intratraqueal/efeitos adversos , Bloqueio Neuromuscular , Orofaringe/lesões , Posicionamento do Paciente , Estudos Prospectivos , Fatores de Risco , Fita Cirúrgica/efeitos adversos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The prevalence of Coronary Atherosclerotic Heart Disease (CASHD) is increasing in India. Several modifiable risk factors contribute directly to this disease burden. Public knowledge of such risk factors among the urban Indian population is largely unknown. This investigation attempts to quantify knowledge of modifiable risk factors of CASHD as sampled among an Indian population at a large metropolitan hospital. METHODS: A hospital-based, cross sectional study was conducted at All India Institute of Medical Sciences (AIIMS), a major tertiary care hospital in New Delhi, India. Participants (n = 217) recruited from patient waiting areas in the emergency room were provided with standardized questionnaires to assess their knowledge of modifiable risk factors of CASHD. The risk factors specifically included smoking, hypertension, elevated cholesterol levels, diabetes mellitus and obesity. Identifying 3 or less risk factors was regarded as a poor knowledge level, whereas identifying 4 or more risk factors was regarded as a good knowledge level. A multiple logistic regression model was used to isolate independent demographic markers predictive of a participant's level of knowledge. RESULTS: 41% of the sample surveyed had a good level of knowledge. 68%, 72%, 73% and 57% of the population identified smoking, obesity, hypertension, and high cholesterol correctly, respectively. 30% identified diabetes mellitus as a modifiable risk factor of CASHD. In multiple logistic regression analysis independent demographic predictors of a good knowledge level with a statistically significant (p < 0.05) adjusted odds ratio (aOR) were: routine exercise of moderate intensity, aOR 8.41 (compared to infrequent or no exercise), no history of smoking, aOR 8.25, and former smokers, aOR 48.28 (compared to current smokers). Although statistically insignificant, a trend towards a good knowledge level was associated with higher levels of education. CONCLUSION: An Indian population in a hospital setting shows a lack of knowledge pertaining to modifiable risk factors of CASHD. By isolating demographic predictors of poor knowledge, such as current smokers and persons who do not exercise regularly, educational interventions can be effectively targeted and implemented as primary and secondary prevention strategies to reduce the burden of CASHD in India.