Versatile gene delivery targeting via Ultrasound and gas Microbubbles

The COVID-19 crisis and the rapid development of highly effective mRNA vaccines opened a new era for gene therapy. While viral vectors were for a long time the only tool for efficient delivery, new non-viral vectors have recently emerged, spawning new opportunities (indications, tissues, etc.). A new one is set to take off thanks to its safety profile, its specificity toward tissues, and its versatility toward both genetic materials and indications. Gas-filled microbubbles (MB), clinically used as ultrasound (US) contrast agents, have proven their benefits in various animal models and clinical applications for targeted delivery of drugs/genes. Herein, we disclose the development of new MB formulations allowing the delivery of various genetic materials at a specific location under the control of an ultrasound probe. We set forth a study to elicit the expression of a foreign enzyme in a liver mouse model. To this aim, MB were systemically co-injected with a Luciferase pDNA (6 to 65 mug) in the tail vein, then Ultrasound were delivered at MB arrival in the liver. The effective pDNA transfection was observed by bioluminescence 24 hours after treatment. Mice were divided into three groups: pDNA alone;pDNA with US;pDNA with US and MBs (n >= 5). The use of our MB allowed increasing the signal up to 5 folds in comparison to the US alone. These results highlight the potential of MB plus US to efficiently deliver locally genetic material without any safety concerns.

Direct Costs of COVID-19 Inpatient Admissions in a Portuguese Tertiary Care University Centre

Background: The COVID-19 pandemic has posed greater financial pressure on health systems and institutions that had to respond to the specific needs of COVID-19 patients while ensuring the safety of the diagnosis and treatment of all patients and healthcare professionals. To assess the financial impact of COVID-19 patients admitted to hospitals, we have characterized the cost of COVID-19 admissions, using inpatient data from a Portuguese Tertiary Care University Centre. Methods: We analysed inpatient data from adult patients diagnosed with COVID-19 who were admitted between March 1, 2020 and May 31, 2020. Admissions were eligible if the ICD-10-CM principal diagnosis was coded U07.1. We excluded admissions from patients under 18 years old, admissions with incomplete records, admissions from patients who had been transferred to or from other hospitals or those whose inpatient stay was under 24 h. Pregnancy, childbirth, and puerperium admissions were also excluded, as well as admissions from patients who had undergone surgery. Results: We identified 223 admissions of patients diagnosed with COVID-19. Most were men (64.1%) and aged 45-64 years (30.5%). Around 13.0% of patients were admitted to intensive care units and 9.9% died in hospital. The average length of hospital stay was 12.7 days (SD = 10.2) and the average estimated cost per admission was EUR 8,177 (SD = 11,534), which represents more than triple the inpatient base price (EUR 2,386). Human resources accounted for the highest proportion of the total costs per admission (50.8%). About 92.4% of the admissions were assigned to Diagnosis Related Group (DRG) 723, whose inpatient price is lower than COVID-19 inpatient costs for all degrees of severity. Conclusion: COVID-19 admissions represent a substantial financial burden for the Portuguese NHS. For each COVID-19 hospitalized patient it would have been possible to treat three other hospitalized patients. Also, the price set for DRG 723 is not adjusted to the cost of COVID-19 patients. These findings highlight the need for additional financial resources for the health system and, in particular, for hospitals that have treated high volumes of hospitalized patients diagnosed with COVID-19. © 2022 The Author(s). Published by S. Karger AG, Basel on behalf of NOVA National School of Public Health.

Panorama of notifications about adverse events and technical complaints related to facemasks

Introduction: In the daily routine of Health Professionals, mainly in the midst of the Sars-CoV-2 pandemic, facemasks are important devices;however, there is no post market control for these products. Objective: Evaluate the Adverse Events (AE) and Technical Complaints (TC) related to facemasks and respirators, to list and categorize the public health problems involving these products. Method: Cross-sectional, descriptive, retrospective and documental study with a quantitative approach, including data from January 2010 to May 2020 available in the Notivisa system. The analyzed data had national coverage and were reclassified, when necessary, according to their category (EA or QT). Results: 443 notifications were included in the study containing 519 claims (AE and TC). The data distribution on the analized decade presented an accentuated decrease;the Southeast region had the highest prevalence of claims in Brazil. Most of the notifying companies were health establishments and the highest prevalence of health events found were Adverse Events that affected the user when fixing strips and nose clips (such as detachment of the nose clip and breaking of the fixation straps during use), indicating serious biosecurity problems. Conclusions: This study characterized the Adverse Events and the Technical Complaints in facemasks focusing on health promotion and indicating the necessity of sanitary monitoring improvement of the products.