COVID-19 pandemic and the quality of antibiotic use in primary care: an interrupted time-series study.

The coronavirus disease-19 pandemic and the related public health mitigation measures have impacted the transmission of infectious diseases; however, their impact on the use of antibacterials has not yet been extensively evaluated. This study evaluated the impact of the pandemic on the consumption patterns of antibacterials for systemic use in primary care in Portugal. An interrupted time-series analysis was performed using the autoregressive integrated moving average model of the antibacterials dispensed in the community pharmacies in Portugal from 1 January 2016 to 30 June 2022. Monthly rates of absolute consumption (all antibacterials for systemic use, and specifically penicillins; cephalosporins; macrolides, lincosamides, and streptogramins; and quinolones) and the relative consumption of antibacterials (penicillins sensitive to ß-lactamase, penicillin combinations including ß-lactamase inhibitors, third- and fourth-generation cephalosporins, fluoroquinolones, and the ratio of broad- to narrow-spectrum antibacterials) were estimated. Antibiotic consumption was expressed in defined daily doses per 1000 inhabitants per day (DID). In Portugal, the consumption of antibacterials (J01) declined sharply immediately after the beginning of the pandemic, having a significant reduction of >5 DID (P < .0001). A similar, short-term impact was found for penicillins (-2.920 DID; P < .0001); cephalosporins (-0.428 DID; P < .0001); macrolides, lincosamides, and streptogramins (-0.681 DID; P = .0021); and quinolones (-0.320 DID; P < .0001). A long-term increase was found for cephalosporins (+0.019 DID per month; P < .0001). Relative consumption changes were only found for third- and fourth-generation cephalosporins (0.0734%). Our study suggests that the coronavirus disease-19 pandemic may have resulted in a decrease in antibiotic use, with no significant changes in the relative dispense. Uncertainties regarding the long-term effects of the pandemic and its impact on the rates of resistance remain.

Cannabidiol and Terpene Formulation Reducing SARS-CoV-2 Infectivity Tackling a Therapeutic Strategy.

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines. Conclusions and Impact: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.

ATENA-A Novel Rapidly Manufactured Medical Invasive Ventilator Designed as a Response to the COVID-19 Pandemic: Testing Protocol, Safety, and Performance Validation.

Background: The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator. Objective: This article aims to demonstrate ATENA's adequate performance and safety for clinical use. Material: ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models. Results: The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo. Conclusion: The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.

Clinical activity of pembrolizumab in metastatic prostate cancer with microsatellite instability high (MSI-H) detected by circulating tumor DNA.

To report a multi-institutional case series of patients with advanced microsatellite instability high (MSI-H) prostate adenocarcinoma identified with clinical cell-free DNA (cfDNA) next-generation sequencing (NGS) testing and treated with immune checkpoint inhibitors. Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months. Four patients (44%) achieved PSA50 after a median of 4 (3-12) weeks after treatment initiation including three patients with >99% PSA decline. Among the patients evaluable for radiographic response (n=5), the response rate was 60% with one complete response and two partial responses. Best response was observed after a median of 3.3 (1.4-7.6) months. At time of cut-off, four patients were still on pembrolizumab while four patients discontinued therapy due to progressive disease and one due to COVID-19 infection. Half of the patients with PSA50 had both MSI-H and pathogenic alterations in BRCA1 and BRCA2 in their G360 assays. The use of liquid biopsy to identify metastatic prostate cancer patients with MSI-H is feasible in clinical practice and may overcome some of the obstacles associated with prostate cancer tumor tissue testing. The robust activity of pembrolizumab in selected patients supports the generalized testing for MSI-H.