Microscopic Droplet Size Analysis (MDSA) of "Five Thieves' Oil" (Olejek Pieciu Zlodziei) Essential Oil after the Nebulization Process.

Nowadays, due to a higher resistance to drugs, antibiotics, and antiviral medicaments, new ways of fighting pathogens are intensively studied. The alternatives for synthesized compositions are natural products, most of which have been known in natural medicine for a long time. One of the best-known and intensively investigated groups are essential oils (EOs) and their compositions. However, it is worth noting that the method of application can play a second crucial part in the effectiveness of the antimicrobial activity. EOs possess various natural compounds which exhibit antimicrobial activity. One of the compositions which is based on the five main ingredients of eucalyptus, cinnamon, clove, rosemary, and lemon is named "five thieves' oil" (Polish name: olejek pieciu zlodziei) (5TO) and is used in natural medicine. In this study, we focused on the droplet size distribution of 5TO during the nebulization process, evaluated by the microscopic droplet size analysis (MDSA) method. Furthermore, viscosity studies, as well as UV-Vis of the 5TO suspensions in medical solvents such as physiological salt and hyaluronic acid, were presented, along with measurements of refractive index, turbidity, pH, contact angle, and surface tension. Additional studies on the biological activity of 5TO solutions were made on the P. aeruginosa strain NFT3. This study opens a way for the possible use of 5TO solutions or emulsion systems for active antimicrobial applications, i.e., for surface spraying.

Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo.

The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by the lactic acid bacterium Leuconostoc mesenteroides B512F. Time of addition assays with SARS-CoV-2 pseudoviruses in in vitro models confirm the inhibitory activity of DSs in the early stages of viral infection (viral entry). In addition, this exopolysaccharide substance also reports broad-spectrum antiviral activity against several enveloped viruses such as SARS-CoV-2, HCoV229E, HSV-1, in in vitro models and in human lung tissue. The toxicity and antiviral capacity of DS from L. mesenteroides was tested in vivo in mouse models which are susceptible to SARS-CoV-2 infection. The described DS, administered by inhalation, a new route of administration for these types of polymers, shows strong inhibition of SARS-CoV-2 infection in vivo, significantly reducing animal mortality and morbidity at non-toxic doses. Therefore, we suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.

Nebulization and COVID-19:Is the risk of spread actual?

The airborne transmission of SARS-CoV-2 has been quickly suggested based on the stability of SARS-CoV-2 in aerosol for 3 hours. Nebulization, by a possible microorganisms contamination and/or by the aerosolization of contaminated particles, may expose health care workers. Thus, various guidelines on nebulization emerged during the SARS-CoV-2 pandemic to ensure a maximal protection. This study aimed to address the risk of airborne transmission in patients hospitalized with severe COVID-19. Ten severe COVID-19 patients were recruited at the admission in the hospital. They were treated by nebulization with a standard single-use jet nebulizer operating at 8 L/min with a T piece connected to a mouthpiece and a filter. Immediately after the first nebulization, the residual solution of each nebulizer was sampled. Then, the nebulizers were refilled with isotonic saline solution to complete the residual volume. The filter was replaced by a BioSampler (SKC 20-mL) loaded with 20 mL phosphatebuffered saline and 0.5% bovine serum albumin. The nebulizer was driven by a compressed air supply, and a 10minnebulization was performed again on the bench. The emitted aerosol was continuously collected during the nebulization. The nominal and emitted dose were sampled. The SARS-CoV-2 viral load was quantified in all samples by RT-PCR. No SARS-CoV-2 RNA was found in any sample for all nebulizations. The result of this study shows no SARS-CoV-2 nebulizers contamination by COVID-19 patients at hospital and does not support the role of nebulizers in terms of aerosol virus dissemination in air. Nevertheless, exhaled virus by the patient itself remains and must be considered independently to the nebulizer.

Isolated tracheobronchial mucormycosis: Report of a case and systematic review of literature

Background: Isolated tracheobronchial mucormycosis (ITBM) is an uncommonly reported entity. Herein, we report a case of ITBM following coronavirus disease 2019 (COVID-19) and perform a systematic review of the literature. Case description and systematic review: A 45-year-old gentleman with poorly controlled diabetes mellitus presented with cough, streaky haemoptysis, and hoarseness of voice 2 weeks after mild COVID-19 illness. Computed tomography and flexible bronchoscopy suggested the presence of a tracheal mass, which was spontaneously expectorated. Histopathological examination of the mass confirmed invasive ITBM. The patient had complete clinical and radiological resolution with glycaemic control, posaconazole, and inhaled amphotericin B (8 weeks). Our systematic review of the literature identified 25 additional cases of isolated airway invasive mucormycosis. The median age of the 26 subjects (58.3% men) was 46 years. Diabetes mellitus (79.2%) was the most common risk factor. Uncommon conditions such as anastomosis site mucormycosis (in two lung transplant recipients), post-viral illness (post-COVID-19 [n = 3], and influenza [n = 1]), and post-intubation mucormycosis (n = 1) were noted in a few. Three patients died before treatment initiation. Systemic antifungals were used in most patients (commonly amphotericin B). Inhalation (5/26;19.2%) or bronchoscopic instillation (1/26;3.8%) of amphotericin B and surgery (6/26;23.1%) were performed in some patients. The case-fatality rate was 50%, primarily attributed to massive haemoptysis. Conclusion: Isolated tracheobronchial mucormycosis is a rare disease. Bronchoscopy helps in early diagnosis. Management with antifungals and control of risk factors is required since surgery may not be feasible. © 2022 Wiley-VCH GmbH.

Novel trehalose-based excipients for stabilizing nebulized anti-SARS-CoV-2 antibody.

COVID-19 is caused by the infection of the lungs by SARS-CoV-2. Monoclonal antibodies, such as sotrovimab, showed great efficiency in neutralizing the virus before its internalization by lung epithelial cells. However, parenteral routes are still the preferred route of administration, even for local infections, which requires injection of high doses of antibody to reach efficacious concentrations in the lungs. Lung administration of antibodies would be more relevant requiring lower doses, thus reducing the costs and the side effects. But aerosolization of therapeutic proteins is very challenging, as the different processes available are harsh and trigger protein aggregation and conformational changes. This decreases the efficiency of the treatment, and can increase its immunogenicity. To address those issues, we developed a series of new excipients composed of a trehalose core, a succinyl side chain and a hydrophobic carbon chain (from 8 to 16 carbons). Succinylation increased the solubility of the excipients, allowing their use at relevant concentrations for protein stabilization. In particular, the excipient with 16 carbons (C16TreSuc) used at 5.6 mM was able to preserve colloidal stability and antigen-binding ability of sotrovimab during the nebulization process. It could also be used as a cryoprotectant, allowing storage of sotrovimab in a lyophilized form during weeks. Finally, we demonstrated that C16TreSuc could be used as an excipient to stabilize antibodies for the treatment against COVID-19, by in vitro and in vivo assays. The presence of C16TreSuc during nebulization preserved the neutralization capacity of sotrovimab against SARS-CoV-2 in vitro; an increase of its efficacy was even observed, compared to the non-nebulized control. The in vivo study also showed the wide distribution of sotrovimab in mice lungs, after nebulization with 5.6 mM of excipient. This work brings a solution to stabilize therapeutic proteins during storage and nebulization, making pulmonary immunotherapy possible in the treatment of COVID-19 and other lung diseases.

Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Coronavirus-mimicking nanoparticles (CorNPs) in artificial saliva droplets and nanoaerosols: Influence of shape and environmental factors on particokinetics/particle aerodynamics.

Severe acute respiratory syndrome coronavirus 2, abbreviated as SARS-CoV-2, has been associated with the transmission of infectious COVID-19 disease through breathing and speech droplets emitted by infected carriers including asymptomatic cases. As part of SARS-CoV-2 global pandemic preparedness, we studied the transmission of aerosolized air mimicking the infected person releasing speech aerosol with droplets containing CorNPs using a vibrating mesh nebulizer as human patient simulator. Generally speech produces nanoaerosols with droplets of <5 µm in diameter that can travel distances longer than 1 m after release. It is assumed that speech aerosol droplets are a main element of the current Corona virus pandemic, unlike droplets larger than 5 m, which settle down within a 1 m radius. There are no systemic studies, which take into account speech-generated aerosol/droplet experimental validation and their aerodynamics/particle kinetics analysis. In this study, we cover these topics and explore role of residual water in aerosol droplet stability by exploring drying dynamics. Furthermore, a candle experiment was designed to determine whether air pollution might influence respiratory virus like nanoparticle transmission and air stability.

Delivery of Epinephrine by Metered-Dose Inhaler for the Treatment of Croup in Children

Study Objective: Croup, also known as laryngotracheobronchitis, is a common pediatric presentation in the emergency department. When children present with moderate or severe croup, epinephrine, either racemic or L-isomer, given by nebulization is considered standard of care. Since the beginning of the SARS-CoV-2 pandemic, many medical institutions have moved away from the delivery of medications by nebulization whenever possible in order to prevent aerosolization of the SARS-CoV-2 virus and infecting others in close proximity. Delivery of respiratory medication by metered-dose inhaler (MDI) was the most commonly adopted method to replace nebulization. Primatene MIST (Armstrong Pharmaceuticals) is an over-the-counter, L-epinephrine MDI. In February 2021, the Pediatric Service Line Pharmacy and Therapeutics Committee of the Northwell Health system approved the use of Primatene MIST in children >= 1 years old presenting to the emergency department with croup as an alternative to nebulized epinephrine. We aim to demonstrate that L-epinephrine administered by MDI is safe and effective in children presenting with moderate croup. Study Design/Methods: We conducted a single-center retrospective chart review study of children 1 to 17 years of age who presented to the emergency department at Cohen Children's Medical Center and were evaluated for suspected croup from March 2021 until May 2022. As part of a surveillance and later reapproval process by the Pediatric Service Line Pharmacy and Therapeutics Committee of the Northwell Health system for Primatene MIST, data was prospectively collected and entered into a REDCap database. This included Westley Croup Score, requirement of additional doses of epinephrine, adverse events, disposition, and return within 48 hours. During the initial rollout, eligible patients were administered 4 puffs through an attached spacer. Following safety review, dosing was increased to 6 puffs. Result(s): A total of 24 pediatric patients with croup received Primatene MIST. The mean age was 3.3 years (SD:2.3 years) and 75% were male. Of the 16 patients who had respiratory viral testing, 19% tested positive for SARS-CoV-2 virus. The median Westley Croup Scores at presentation was 3 (IQR:2,3;Range:2-5), 0 (IQR:0,1;Range:0-4) at 30 minutes and 0 (IQR:0,1;Range:0-3) at 120 minutes following Primatene MIST administration. A second dose of epinephrine (nebulized or MDI) was administered to 7 patients (29.2%;CI:14.9%-49.2%). Only 1 patient (4.2%) was admitted and 1 (4.2%) returned within 48 hours. There were no reported adverse events. Conclusion(s): Epinephrine administered by MDI is a safe and effective treatment for moderate croup. It should be considered as an alternative to nebulized epinephrine when there are concerns for infectious aerosolization. No, authors do not have interests to disclose Copyright © 2022

Use of High-Dose Nebulized Colistimethate in Patients with Colistin-Only Susceptible Acinetobacter baumannii VAP: Clinical, Pharmacokinetic and Microbiome Features.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the 'real life' clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32-57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100-164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75-14] vs. 7 [4-13] days, OR (95% CI): 1.069 (1.003-1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

Community-acquired Methicillin-resistant Staphylococcus aureus Pneumonia and Parapneumonic Effusion in a Male Patient with Diabetes: A Case Report

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a primary health concern. They are commonly differentiated as hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) and community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections, based on their epidemiology, susceptibility findings, and molecular typing patterns. Therefore, appropriate contact precautions and isolation measures should be implemented. CA-MRSA mostly causes skin and soft-tissue infections, but the probability and incidence of it causing sepsis and invasive infections have increased dramatically in recent years. In this study, we report a case of CA-MRSA pneumonia with pan-pneumonic effusion in a 59-year-old male diabetic patient with preexisting comorbidities such as diabetic ketoacidosis and non-ST elevated myocardial infarction. The early reporting of the organism's identity and its antimicrobial susceptibility, as well as timely initiation of antibiotic therapy, aided in the successful management and cure of the patient.

EFFICIENCY OF A NEBULIZER FILTER KIT TO PREVENT ENVIRONMENTAL CONTAMINATION DURING NEBULIZER THERAPY

SESSION TITLE: Respiratory Care: Oxygen, Rehabilitation, and Inhalers SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: The SARS-CoV-2 pandemic has highlighted the need to avoid environmental contamination with aerosols. To aid in this, the addition of a filter kit is intended to capture any exhaled aerosol. To determine the aerosol amounts emitted to the environment during nebulizer therapy several nebulizers were evaluated to test the efficiency of the nebulizer filter system. METHODS: The MaxiNeb® Duo, Circulaire® II and AeroEclipse® II BAN™ Nebulizer were operated at 50PSIG with their optional filter kits (n=5). Each device was evaluated with 2.5mg/3.0mL fill of albuterol and connected to a simulator mimicking adult tidal breathing. In addition to inspiratory and expiratory filters, the nebulizer was placed under an extraction system to capture any aerosol emitted through leakages or exhalation. Albuterol assay was undertaken by HPLC-UV spectrophotometry. RESULTS: The mass of albuterol captured from the extraction system with the MaxiNeb® Duo, Circulaire® II and AeroEclipse® II BAN™ Nebulizer was found to be 0.5±0.2, 1.5±0.6 and 0.0±0.0% of the initial dose respectively. CONCLUSIONS: The BAN™ Nebulizer without filter kit has previously reported environmental losses of just under 3%ꝉ so it is in keeping that the addition of the filter kit eliminated all losses for this device. The other two nebulizers emitted small amounts of aerosol even when a filter kit was used. CLINICAL IMPLICATIONS: If the laboratory results for the nebulizer / filter systems which did not eliminate all environmental emissions were replicated in a clinical setting, there would likely need to be an assessment performed into the potential risk to staff and patients. ꝉ Efficiency of a Nebulizer Filter Kit to Prevent Environmental Contamination During Nebulizer Therapy – presented at European Respiratory Society Meeting 2021 DISCLOSURES: Employee relationship with Trudell Medical International Please note: 27 years by Mark Nagel, value=Salary Employee relationship with Trudell Medical International Please note: >$100000 by Jason Suggett, value=Salary

A BLOODY MASQUERADE: A CURIOUS CASE OF HEMOPTYSIS

SESSION TITLE: Variety in Chest Infections Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Actinomyces is a Gram-positive anaerobic and micro aerophilic filamentous bacillus that normally colonize the human mouth and digestive and urogenital tracts. They most commonly cause cervical and abdominopelvic infections and rarely pulmonary actinomycosis. CASE PRESENTATION: 67-year-old female with past medical history of recurrent DVT with IVC filter placement, non- ischemic cardiomyopathy, atrial fibrillation, 40 pack year history, recent COVID19 infection, lung nodules & COPD presented with complaint of coughing up blood associated with chest pain for the past 2 days. She had a low-grade fever with stable vitals with preliminary labs showing she was anemic and had reactive leukocytosis. She was recommended to hold oral anticoagulation and follow-up outpatient during when her symptoms worsened. On admission she was started on tranexamic acid nebulization for hemostasis and underwent CTA chest which showed no evidence for pulmonary embolism but commented on a right lower lobe perihilar 12.5 mm mass which has increased in size compared to previous scans. Patient underwent bronchoscopy which showed generalized edema of the tracheobronchial tree with bleeding from superior segment of the right lower lobe bronchus with no visualization of mass. PET scan showed hyper-metabolic lung mass with concerns for malignancy. CT guided biopsy of nodule was done and was not staining for malignant cells, acid fast bacilli with no fungal or bacterial growth. Blood cultures and Karius Digital cultures were also negative. She began expectorating blood clots despite being on treatment and cardiothoracic surgery was consulted. A partial lobectomy with lysis of adhesions of the right lower lobe was done. Specimen sent to pathology showed no evidence for malignancy but instead elicited a contained pulmonary abscess containing filamentous bacteria with parenchymal inflammation with areas of chronic hemorrhagic fibrosing pleuritis and hilar thrombi. She was diagnosed with pulmonary actinomycosis and started on IV 24,000,000 IU penicillin. She underwent a panoramic dental x-ray which was read as suboptimal dentition with multiple missing teeth and did not identify a source. Patient symptoms resolved post lobectomy and since discharged on long course of antibiotics. She continued to have no more episodes of hemoptysis. DISCUSSION: Hemoptysis as a symptom of pulmonary actinomycosis is a rather rare presentation. Actinomycosis causes cavities, nodules, and pleural effusions. It is commonly mistaken for chronic suppurative lung disease and sometimes malignancy. Isolation and identification occur only a minority of cases with a high culture failure rate due to previous antibiotic therapy, inadequate incubation time or culture conditions. CONCLUSIONS: Due to it's variable presentation pulmonary actinomyces has a large overlap with other diseases but must be considered in the differential of unexplained hemoptysis. Reference #1: Hemoptysis secondary to actinomycosis: A rare presentation. PMID: 24778485 PMCID: PMC3999682 DOI: 10.4103/0970-2113.129864 DISCLOSURES: No relevant relationships by Victoria Famuyide No relevant relationships by rukhsaar khanam

Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis.

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 µm as measured by cascade impaction, and a volumetric median diameter of 4.09 µm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

Effect of a hydrogen peroxide gas-plasma sterilization on physical integrity and quality of N95 respirators: An experimental study during the COVID-19 pandemic

Background: N95 respirators have prevented transmission among health-care workers during the COVID-19 pandemic. During times of intense shortage of respirators and border closures during the pandemic, re-use strategies with available decontamination methods were necessitated. This in-house experimental study evaluated the effect of hydrogen peroxide gas-plasma sterilization on respirators and helped establish an evidence-based protocol for their re-use in a resource-poor setting. Materials and Methods: A three-dimensional experimental model using saline nebulization as the aerosol exposure and a particle counter to measure the filtration of particles through the mask pre- and post-sterilization was used. Multiple cycles of plasma sterilization were done till the physical integrity/fit was lost. Total filtration volume was used as a surrogate marker to assess the filtration efficiency (FE). Results: The total volume of particles filtered on a 3M respirator was 99.9%. Unused Halyard and Venus respirators were compared against 3M and found to have FE of 99.9% and 60.5%, respectively. After repeated sterilization cycles, the total volume of particles filtered was 59.3% for Halyard in the seventh cycle and 36.2% for Venus in the fifth cycle. When the physical integrity and fit was tested, the appropriate fit was lost after eight cycles of sterilization for Venus and was not lost for Halyard even after the tenth cycle. Conclusion: This low-cost experimental study helped implement an effective and safe decontamination strategy for safe re-use of N95 respirators in an emergent situation with no access to commercial testing in a resource poor health-care setting during the pandemic.

Effectiveness of air-purifying devices and measures to reduce the exposure to bioaerosols in school classrooms.

The SARS-CoV-2 pandemic, which suddenly appeared at the beginning of 2020, revealed our knowledge deficits in terms of ventilation and air pollution control. It took many weeks to realize that aerosols are the main route of transmission. The initial attempt to hold back these aerosols through textile masks seemed almost helpless, although there is sufficient knowledge about the retention capacity of fabric filters for aerosols. In the absence of a sufficient number of permanently installed heating, ventilation, and air conditioning systems, three main approaches are pursued: (a) increasing the air exchange rate by supplying fresh air, (b) using mobile air purifiers, and (c) disinfection by introducing active substances into the room air. This article discusses the feasibility of these different approaches critically. It also provides experimental results of air exchange measurements in a school classroom that is equipped with a built-in fan for supplying fresh air. With such a fan and a window tilted at the appropriate distance, an air exchange rate of 5/h can be set at a low power level and without any significant noise pollution. Heat balance calculations show that no additional heat exchanger is necessary in a normal classroom with outside temperatures above 10°C. Furthermore, a commercial mobile air purifier is studied in a chamber and a test room setup in order to examine and evaluate the efficiency of such devices against viable viruses under controlled and realistic conditions. For this purpose, bacteriophages of the type MS2 are used. Both window ventilation and air purifiers were found to be suitable to reduce the concentration of phages in the room.

Perioperative Concerns for Patients with Prior SARS-CoV-2 Infection: Our Experience

Methodology and case description: Case 1: A 55-year-old hypertensive male with complaints of chest pain presented to the cardiology department. He underwent angiography to reveal triple vessel disease and was scheduled for coronary artery bypass graft surgery. During preoperative evaluation, patient gave a history of having suffered from mild COVID-19, getting cured with conservative management under home isolation 3 months back. Examination revealed bilateral basal crepitations. Chest X-ray was indicative of fibrosis basal areas of both lungs (right > left) which was confirmed by HRCT chest. Preoperatively the patient was optimised with antifibrotic agent nintedanib and methylprednisolone. He was reviewed after 1 month and had shown significant-resolution radiologically as well as clinically (improved breath holding time, saturation and lung auscultation). Intraoperative course was uneventful and the patient was ventilated with low tidal volume. Postoperatively, the patient was extubated on day 1. Patient experienced difficulty in expectoration which was improved by N-acetyl cysteine administered intravenously and via nebulisation along with active vigorous physiotherapy. Patient was discharged on the 7th postoperative day. Case 2: A 37-yearold female, a known case of severe mitral stenosis, moderate pulmonary hypertension, moderate tricuspid regurgitation was under conservative management with diuretics and beta-blockers and was being planned for mitral valve replacement. The patient had developed COVID-19 infection 1 month back and was treated under home isolation and conservative management. However, the patient presented with an increase in exercise intolerance post COVID infection. Suspecting the possibility of fluid overload/ heart failure and pulmonary hypertension, the diuretic dose was increased post admission, but to no avail. Chest X-ray and HRCT chest were done which highlighted the possibility of allergic bronchopulmonary aspergillosis;which has been described as one of the rare findings coexisting with active COVID-19 infection. This was confirmed by the serum IgE levels and presence of eosinophilia in the complete blood picture. The patient was initiated on itraconazole and methylprednisolone which resulted in improvement in breathlessness over the next 3 weeks. The patient was subsequently posted for surgical replacement of the mitral valve. Intra-operative and post-operative course was uneventful and the patient was discharged on 5th post-operative day. Conclusion: These 2 cases who had suffered from mild COVID-19 infection presented significant challenges for safe intra- and post-operative conduct of anaesthesia. These challenges were overcome by efficient prehabilitation and optimisation of the patient and optimal post-operative critical care. Intra-operative course is often just a small segment of the overall hospital course of the patient and the role of critical care in the pre-surgical, extra-hospital care along with post-operative care needs acknowledgement and recognition.

Preparation and Characterization of Disulfiram and Beta Cyclodextrin Inclusion Complexes for Potential Application in the Treatment of SARS-CoV-2 via Nebulization.

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl ß-cyclodextrin (HP) and sulfobutyl ether ß-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS-CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD-DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS-CD inclusion complexes against SARS-CoV-2 via nebulization.

Causal inference during a pandemic: evidence on the effectiveness of nebulized ibuprofen as an unproven treatment for COVID-19 in Argentina

Many medical decisions during the pandemic were made without the support of causal evidence obtained in clinical trials. We study the case of nebulized ibuprofen (NaIHS), a drug that was extensively used on COVID-19 patients in Argentina amidst wild claims about its effectiveness and without regulatory approval. We study data on 5,146 patients hospitalized in 11 health centers spread over 4 provinces, of which a total of 1,019 (19.8%) received the treatment. We find a large, negative and statistically significant correlation between NaIHS treatment and mortality using inverse probability weighting estimators. We consider several threats to identification, including the selection of "low" risks into NaIHS, spillovers affecting patients in the control group, and differences in the quality of care in centers that use NaIHS. While the negative correlation appears to be, broadly, robust, our results are best interpreted as emphasizing the benefits of running a randomized controlled trial and the challenges of incorporating information produced in other, less rigorous circumstances.

Application of an Ultrasonic Nebulizer Closet in the Disinfection of Textiles and Footwear.

The emergence of the coronavirus disease 2019 (COVID-19) pandemic highlighted the importance of disinfection processes in health safety. Textiles and footwear have been identified as vectors for spreading infections. Therefore, their disinfection can be crucial to controlling pathogens' dissemination. The present work aimed to evaluate the effectiveness of a commercial disinfectant aerosolized by an ultrasonic nebulizer closet as an effective method for disinfecting textiles and footwear. The disinfection was evaluated in three steps: suspension tests; nebulization in a 0.08 m3 closet; nebulization in the upscaled 0.58 m3 closet. The disinfection process of textiles and footwear was followed by the use of bacteriophages, bacterial spores, and bacterial cells. The disinfection in the 0.58 m3 closet was efficient for textiles (4 log reduction) when bacteriophage Lambda, Pseudomonas aeruginosa, and Bacillus subtilis were used. The footwear disinfection was achieved (4 log reduction) in the 0.08 m3 closet for Escherichia coli and Staphylococcus aureus. Disinfection in an ultrasonic nebulization closet has advantages such as being quick, not wetting, being efficient on porous surfaces, and is performed at room temperature. Ultrasonic nebulization disinfection in a closet proves to be useful in clothing and footwear stores to prevent pathogen transmission by the items' widespread handling.

Safety and Systemic Exposure of Hydroxychloroquine in Healthy Volunteers After Inhalation Administration

The anti-inflammatory and antiviral effects of hydroxychloroquine have not been demonstrated in clinical trials for the treatment of COVID-19. A possible reason for the failure is low local exposure in the lungs after p.o. or i.v. administration. In the Phase 1 study, the aim was to test the pharmacokinetics and safety of inhaled hydroxychloroquine after nebulization. In 6 healthy volunteers, we determined the pharmacokinetics after a single administration of 10 mg hydroxychloroquine from 19 blood samples collected at the following times: before nebulization and 2, 5, 10, 15, 20, 25, 30, 45, and 60 min, and 1:15, 1:30, 2:00, 2:30, 3:00, 4:00, 8:00, 12:00, and 24:00 hr after the start of nebulization. On Day 5, we determined the pharmacokinetics after repeated administration of 20 mg once daily from 12 samples taken at the following times: before nebulization and 5, 10, 20, 30, 45, and 60 min, and 2, 4, 8, 12, and 24 hr after the start of nebulization. Safety was assessed by observing biochemical parameters, blood count, and clinical parameters including ECG and blood pressure. After a single administration, the mean ± SD Cmax, T1/2, and AUC0-24 values were 5633.6 ± 2924.8 pg/ml, 11.7 ± 1.3 hr, and 6588.4 ± 1252.2 pg/ml*hr, respectively. After repeated administration on Day 5 the respective values were 4807.7 ± 1708.7 pg/ml, 14.83 ± 3.41 hr, and 26801.0 ± 8217.8 pg/ml*hr. We found no significant difference between the pretreatment and posttreatment values of safety parameters and they did not deviate outside the physiological range. We observed only minor adverse events related to the bitter taste of hydroxychloroquine. There were no systemic or respiratory adverse reactions. We have demonstrated acceptable safety of the inhaled route of administration of hydroxychloroquine in this dose group. [ FROM AUTHOR] Copyright of Acta Facultatis Pharmaceuticae Universitatis Comenianae is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)