Pharmacokinetics of cefiderocol during extracorporeal membrane oxygenation: A case report.

Patients with extracorporeal membrane oxygenation (ECMO) support do frequently receive broad-spectrum antibiotics, due to the high frequency of infection by multidrug resistant microorganisms. The extracorporeal circuit can alter the pharmacokinetics (PK) of administered drugs, and in the case of antibiotics this may lead to treatment failure. Cefiderocol is a new cephalosporin that exhibits excellent in vitro activity against many multidrug-resistant (MDR) microorganisms, but there is no published data about the modifications of its PK in patients with ECMO support. Herein we report the results of a pharmacokinetic investigation of cefiderocol in a critically ill patient receiving extracorporeal respiratory support.

Use of chronic medications and risk of severe death due to COVID-19 in hospitalised patients.

OBJECTIVES: To evaluate the potential association between chronic exposure to medication and death related to COVID-19. METHODS: This is a retrospective cross-sectional study that included all patients hospitalised due to COVID-19 from 11 March to 4 June 2020 in our centre. Chronic patient medication was classified by the Anatomical Therapeutic Chemical (ATC) classification; demographic and clinical data were analysed. Multivariate logistic regression models were used to estimate the adjusted odds ratios (aOR) of death for each drug exposure; each aOR represents an independent model adjusted by clinical factors related to COVID-19 mortality. RESULTS: The study included 978 patients with a mean (SD) age of 64.5 (17.7) years who were predominantly male (531, 54.3%). Of all 978 patients, 182 (18.61%) died during the follow-up of the study. The most common Charlson Comorbidity Index (CCI) was 0, 4.2% were smokers, 16.7% were obese, 47.4% had hypertension, and 19.4% were diabetic. Most patients (70.8%) were prescribed at least one treatment, 32.5% used >5 treatments, and 8.6% >10. Our data suggest that COVID-19 hospitalised patients taking trimethoprim and analogues, leukotriene receptor antagonists, calcineurin inhibitors, aldosterone antagonists, selective immunosuppressants, propulsives, insulins and analogues, and benzodiazepine derivatives have a higher risk of death. CONCLUSIONS: This study investigated the association between chronic exposure to drugs and the risk of death in COVID-19 patients. Our results have shed some light on the impact of chronic drug exposure on the risk of severe COVID-19; however, further research is needed to increase the understanding about its relevance.

Diagnosis of synchronous pancreatic and ampullary adenocarcinomas during the COVID-19 pandemic.

Multiple primary tumors occur in 5-10 % of the population. However, synchronic neoplasms diagnosed within six months of one another is a rarity. We report the case of a patient initially diagnosed with a pancreatic cyst and a synchronous pancreatic and ampullary adenocarcinoma eleven months later.

Severe Lymphopenia as a Predictor of COVID-19 Mortality in Immunosuppressed Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a high mortality in certain group of patients. We analysed the impact of baseline immunosuppression in COVID-19 mortality and the role of severe lymphopenia in immunocompromised subjects. METHODS: We analysed all patients admitted with COVID-19 in a tertiary hospital in Madrid between March 1st and April 30th 2020. Epidemiological and clinical data, including severe lymphopenia (<500 lymphocytes/mm3) during admission, were analysed and compared based on their baseline immunosuppression condition. RESULTS: A total of 1594 patients with COVID-19 pneumonia were hospitalised during the study period. 166 (10.4%) were immunosuppressed. Immunocompromised patients were younger (64 vs. 67 years, p = 0.02) but presented higher rates of hypertension, diabetes, heart, neurological, lung, kidney and liver disease (p < 0.05). They showed more severe lymphopenia (53% vs 24.1%, p < 0.001), lower SapO2/FiO2 ratios (251 vs 276, p = 0.02) during admission and higher mortality rates (27.1% vs 13.5%, p < 0.001). After adjustment, immunosuppression remained as an independent factor related to mortality (Odds Ratio (OR): 2.24, p < 0.001). In the immunosuppressed group, age (OR = 1.06, p = 0.01), acute respiratory distress syndrome (ARDS) (OR = 12.27, p = 0.017) and severe lymphopenia (OR = 3.48, p = 0.04) were the factors related to high mortality rate. CONCLUSION: Immunosuppression is an independent mortality risk factor in COVID-19. Severe lymphopenia should be promptly identified in these patients.

Incidence and risk factors for early readmission after hospitalization for SARS-CoV-2 infection: results from a retrospective cohort study.

PURPOSE: We aim to assess risk factors related to early readmission in previous hospitalized patients with COVID-19. METHODS: We analyzed a retrospective cohort of patients with laboratory-confirmed COVID-19 admitted to Vall d'Hebron University Hospital, Barcelona, Spain. Early readmission was defined as the need for hospitalization within a period of 60 days after discharge. A descriptive analysis of the readmission was performed, including hospitalization outcome. We also performed a multivariate logistic regression to define risk factors for readmission RESULTS: A total of 629 patients were followed up during 60 days with a readmission cumulative incidence of 5.4% (34 out of 629) and an incidence rate of 0.034 person-years. Main reasons for readmission were respiratory worsening (13, 38.2%), decompensation of previous disease (12, 35.3%) or infectious complications (6, 17.6%). Median time to readmission was 12 days (interquartile range 7-33 days). Prior diagnosis of heart failure (OR 4.09; 95% CI 1.35-12.46; p = 0.013), length of stay during index admission greater than 13 days (OR 2.72; 95% CI 1.21-6.12; p = 0.015), treatment with corticosteroids (OR 2.39; 95% CI 1.01-5.70; p = 0.049) and developing pulmonary thromboembolism (OR 11.59; 95% CI 2.89-46.48; p = 0.001) were the risk factors statistically associated with early readmission. CONCLUSION: Readmission cumulative incidence was 5.4%. Those patients with prior diagnosis of heart failure, length of stay greater than 13 days, treated with corticosteroids or who developed pulmonary thromboembolism might benefit from close monitoring after being discharged.

Bad Air Can Also Kill: Residential Indoor Air Quality and Pollutant Exposure Risk during the COVID-19 Crisis.

During the first outbreak of the SARS-CoV-2 pandemic the population, focusing primarily on the risk of infection, was generally inattentive to the quality of indoor air. Spain, and the city of Madrid in particular, were among the world's coronavirus hotspots. The country's entire population was subject to a 24/7 lockdown for 45 days. This paper describes a comparative longitudinal survey of air quality in four types of housing in the city of Madrid before and during lockdown. The paper analysed indoor temperatures and variations in CO2, 2.5 µm particulate matter (PM2.5) and total volatile organic compound (TVOC) concentrations before and during lockdown. The mean daily outdoor PM2.5 concentration declined from 11.04 µg/m3 before to 7.10 µg/m3 during lockdown. Before lockdown the NO2 concentration values scored as 'very good' 46% of the time, compared to 90.9% during that period. Although the city's outdoor air quality improved, during lockdown the population's exposure to indoor pollutants was generally more acute and prolonged. Due primarily to concern over domestic energy savings, the lack of suitable ventilation and more intensive use of cleaning products and disinfectants during the covid-19 crisis, indoor pollutant levels were typically higher than compatible with healthy environments. Mean daily PM2.5 concentration rose by approximately 12% and mean TVOC concentration by 37% to 559%. The paper also puts forward a series of recommendations to improve indoor domestic environments in future pandemics and spells out urgent action to be taken around indoor air quality (IAQ) in the event of total or partial quarantining to protect residents from respiratory ailments and concomitantly enhanced susceptibility to SARS-CoV-2, as identified by international medical research.

COVID-19 in Solid Organ Transplantation: A Matched Retrospective Cohort Study and Evaluation of Immunosuppression Management.

BACKGROUND: The epidemiological and clinical characteristics of solid organ transplant (SOT) patients during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic remains unclear. We conducted a matched retrospective cohort study to compare clinical outcomes among SOT recipients with the general population and to assess immunosuppression management. METHODS: Adult SOT recipients with laboratory polymerase chain reaction-confirmed SARS-CoV-2 infection admitted to a tertiary-care hospital in Barcelona, Spain, from March 11 to April 25, 2020, were matched to controls (1:4) on the basis of sex, age, and age-adjusted Charlson's Index. Patients were followed for up to 28 days from admission or until censored. Primary endpoint was mortality at 28 days. Secondary endpoints included admission to the intensive care unit and secondary complications. Drug-drug interactions (DDI) between immunosuppressants and coronavirus disease 2019 (COVID-19) management medication were collected. RESULTS: Forty-six transplant recipients and 166 control patients were included. Mean (SD) age of transplant recipients and controls was 62.7 (12.6) and 66.0 (12.7) years, 33 (71.7%) and 122 (73.5%) were male, and median (interquartile range) Charlson's Index was 5 (3-7) and 4 (2-7), respectively. Mortality was 37.0% in SOT recipients and 22.9% in controls (P = 0.51). Thirty-three (71.7%) patients underwent transitory discontinuation of immunosuppressants due to potential or confirmed DDI. CONCLUSIONS: In conclusion, hospitalized SOT recipients with COVID-19 had a trend toward higher mortality compared with controls, although it was not statistically significant, and a notable propensity for DDI.

Pandemics and Traditional Plant-Based Remedies. A Historical-Botanical Review in the Era of COVID19.

Pandemics are as old as humanity and since ancient times we have turned to plants to find solutions to health-related problems. Traditional medicines based mostly on plants are still the only therapeutic possibility in many developing countries, but even in the richest ones, herbal formulation currently receives increased attention. Plants are natural laboratories whose complex secondary metabolism produces a wealth of chemical compounds, leading to drug discovery - 25% of widespread use drugs are indeed of plant origin. Their therapeutic potential is even bigger: although many plant-based compounds show inhibitory effects against a myriad of pathogens, few reach the stage of clinical trials. Their mechanism of action is often unknown, yet traditional plant-based remedies have the advantage of a long-term experience in their use, usually of hundreds to thousands of years, and thus a precious experience on their safety and effects. Here I am providing a non-systematic historical-botanical review of some of the most devastating pandemics that humanity has faced, with a focus on plant therapeutic uses. I will revisit the Middle Ages black death, in which a plant-based lotion (the four thieves vinegar) showed some effectiveness; the smallpox, a viral disease that lead to the discovery of vaccination but for which the native Americans had a plant ally, an interesting carnivorous plant species; tuberculosis and the use of garlic; the Spanish flu and the widespread recommendation of eating onions, among other plant-based treatments; and malaria, whose first effective treatment, quinine, came from the bark of a Peruvian tree, properties already known by the Quechua people. Synthetic analogues of quinine such as chloroquine or hydroxychloroquine are now being revisited for the treatment of COVID19 symptoms, as they are artemisinin and derivatives, other plant-based compounds effective against malaria. Finally, I will give some hints on another facet of plants to aid us in the prevention of infectious diseases: the production of biotechnological plant-based vaccines. Altogether, my aim is to stress the significant role of plants in global health (past, present and future) and the need of enhancing and protecting the botanical knowledge, from systematics to conservation, from ecology to ethnobotany.

Aerosol box for intubation of patients with suspected COVID-19: simulation study

Introduction: Endotracheal intubation is a procedure associated with a high level of exposure to the COVID-19 virus. This has led to the search of alternatives to reduce the risk of contamination, including the so-called aerosol box. Objective: To compare time and difficulty of orotracheal intubation when using the aerosol box in a simulated setting. Methodology: Observational study conducted with the participation of 33 anesthetist physicians and anesthesia residents;groups were compared in terms of time and intubation difficulty using a conventional Macintosh laryngoscope and the McGRATH™ MAC (Medtronic) videolaryngoscope with or without aerosol box. In order to determine performance with the intubation maneuver, crude hazard ratios were estimated, and a Cox multivariate regression model was built, adjusted by anesthetist years of experience and difficulties during the procedure. Results: On average, the aerosol box increased intubation time by 7.57 seconds (SD 8.33) when the videolaryngoscope was used, and by 6.62 (SD 5.74) with the Macintosh. Overall, 132 intubations were performed, with 121 successful and 6 failed first-time attempts (4 with the use of the aerosol box);16 participants (48.48%) reported difficulty handling the box. With the use of the Macintosh, intubation was found to be faster than with the videolaryngoscope (cHR: 1.36 [95% CI 0.64-2.88];adjusted HR: 2.20 [95% CI 0.73-6.62]). Conclusions: The use of the aerosol box and personal protective equipment in a simulation setting hinders the intubation maneuver and may result in protracted execution time. (English) [ABSTRACT FROM AUTHOR] Introducción: La intubación endotraqueal es un procedimiento que se relaciona con alto nivel de exposición al virus de COVID-19, llevando a la búsqueda de alternativas para disminuir el riesgo de contaminación, entre ellas la llamada Caja de aerosoles. Objetivo: Comparar el tiempo y dificultad en la intubación orotraqueal usando la caja de aerosoles en escenarios simulados. Metodología: Estudio observacional, con participación de 33 médicos anestesiólogos y residentes de anestesia;se compararon los grupos en tiempo y dificultad de intubación con uso de laringoscopio convencional Macintosh y videolaringoscopio McGRATH™ MAC (Medtronic) utilizando la caja de aerosoles y sin ella. Para determinar el rendimiento en la maniobra de intubación se calcularon Hazard ratios crudos, se construyó modelo multivariado de Regresion de Cox ajustado por años de experiencia como anestesiólogo y dificultades durante el procedimiento. Resultados: La caja de aerosoles aumentó en promedio el tiempo en segundos para la intubación con videolaringoscopio en 7,57 (DE: 8,33) y con Macintosh 6,62 (DE: 5,74). Se llevaron a cabo 132 intubaciones, 121 exitosas en el primer intento y 6 fallidas (4 con el uso de la caja de aerosoles). 16 participantes reconocieron alguna dificultad al manipular la caja (48,48 %). Con el uso de Macintosh se identificó tendencia a la intubación más rápido que con el videolaringoscopio (HRc: 1,36 [IC 95 %: 0,64-2,88];HR ajustado: 2,20 [IC 95 %: 0,73-6,62]). Conclusiones: Utilizar la caja de aerosoles y equipo de protección personal en un escenario simulado dificulta la maniobra de intubación y puede prolongar el tiempo de ejecución. (Spanish) [ABSTRACT FROM AUTHOR] Copyright of Colombian Journal of Anesthesiology / Revista Colombiana de Anestesiología is the property of Sociedad Colombiana de Anestesiologia y Reanimacion 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 abstract 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 abstract. (Copyright applies to all Abstracts.)