RESUMEN
BACKGROUND: We aimed to examine the role played by the COVID-19 infection in patients' death and to determine the proportion of patients for whom it was a major contributor to death. METHODS: We included patients ≥50 years old who were hospitalized with COVID-19 infection and died between March 1, 2020 and September 30, 2020 in a tertiary medical center. We considered COVID-19 infection to be a major cause for death if the patient had well-controlled medical conditions and death was improbable without coronavirus infection, and a minor cause for death if the patient had serious illnesses and had an indication for palliative care. RESULTS: Among 243 patients, median age was 80 (interquartile intervals: 72-86) and 40% were female. One in two had moderate or severe frailty and 41% had dementia. Nearly 60% of the patients were classified as having advanced, serious illnesses present prior to the hospitalization, with death being expected within 12 months, and among this group 39% were full code at admission. In the remaining 40% of patients, deaths were classified as unexpected based on patients' prior conditions, suggesting that COVID-19 infection complications were the primary contributor to death. CONCLUSIONS: For slightly less than half (40%) of patients who died of complications of COVID-19, death was an unexpected event. Among the 60% of patients for whom death was not a surprise, our findings identify opportunities to improve end-of-life discussions and implement shared decision-making in high-risk patients early on or prior to hospitalization.
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COVID-19 , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos , SARS-CoV-2RESUMEN
Objectives: To examine the current state of practice of oxygen (O2) supplementation in adults hospitalized in a tertiary hospital admitted to medical-surgical floors.Methods: We recorded: the proportion of patients on O2; their peripheral O2 saturation (SpO2); if the SpO2 was within, above, or below the target range; if patients had an order for O2 supplementation and a target SpO2 range.Results: Among 811 hospitalized patients, 153 (19%) were on supplemental O2. Forty-nine percent were in the recommended range, 55% above, and 1% below. All patients with COPD on O2 supplementation had a SpO2 of more than 92% exposing them to the risk of hypercarbia. Only 43% of patients on oxygen had an associated order and only 52% of patients with an O2 order had an order for a goal SpO2 range.Conclusions: Our results demonstrate widespread hyperoxia among hospitalized patients and that oxygen, a very common therapy, is being administered frequently without any written order. These findings highlight the opportunity to implement safe prescribing measures for O2, similar to other prescribed medications.
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Hipoxia/terapia , Terapia por Inhalación de Oxígeno/normas , Centros de Atención Terciaria , Registros Electrónicos de Salud , Humanos , Massachusetts , Administración del Tratamiento FarmacológicoRESUMEN
E-101 solution is a first-in-class myeloperoxidase-mediated antimicrobial developed for topical application. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase (GO), glucose, sodium chloride, and specific amino acids in an aqueous solution. Once activated, the reactive species hydrogen peroxide (H2O2), hypochlorous acid, and singlet oxygen are generated. We evaluated the treatment effects of E-101 solution and its oxidative products on ultrastructure changes and microbicidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli Time-kill and transmission electron microscopy studies were also performed using formulations with pMPO or GO omitted. The glutathione membrane protection assay was used to study the neutralization of reactive oxygen species. The potency of E-101 solution was also measured in the presence of serum and whole blood by MIC and minimal bactericidal concentration (MBC) determinations. E-101 solution demonstrated rapid bactericidal activity and ultracellular changes in MRSA and E. coli cells. When pMPO was omitted, high levels of H2O2 generated from GO and glucose demonstrated slow microbicidal activity with minimal cellular damage. When GO was omitted from the formulation, no antimicrobial activity or cellular damage was observed. Protection from exposure to E-101 solution reactive oxygen species in the glutathione protection assay was competitive and temporary. E-101 solution maintained its antimicrobial activity in the presence of inhibitory substances, such as serum and whole blood. E-101 solution is a potent myeloperoxidase enzyme system with multiple oxidative mechanisms of action. Our findings suggest that the primary site where E-101 solution exerts microbicidal action is the cell membrane, by inactivation of essential cell membrane components.
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Antibacterianos/química , Antibacterianos/farmacología , Peroxidasa/química , Peroxidasa/farmacología , Animales , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Escherichia coli/efectos de los fármacos , Escherichia coli/metabolismo , Glucosa Oxidasa/química , Glucosa Oxidasa/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/química , Especies Reactivas de Oxígeno/farmacología , PorcinosRESUMEN
The abundant larval transcript (ALT-2) protein is present in all members of the Filarioidea, and has been reported as a potential candidate antigen for a subunit vaccine against lymphatic filariasis. To assess the potential for vaccine escape or heterologous protection, we examined the evolutionary selection acting on ALT-2. The ratios of nonsynonymous (K(a)) to synonymous (K(s)) mutation frequencies (ω) were calculated for the alt-2 genes of the lymphatic filariasis agents Brugia malayi and Wuchereria bancrofti and the agents of river blindness and African eyeworm disease Onchocerca volvulus and Loa loa. Two distinct Bayesian models of sequence evolution showed that ALT-2 of W. bancrofti and L. loa were under significant (P<0.05; P < 0.001) diversifying selection, while ALT-2 of B. malayi and O. volvulus were under neutral to stabilizing selection. Diversifying selection as measured by ω values was notably strongest on the region of ALT-2 encoding the signal peptide of L. loa and was elevated in the variable acidic domain of L. loa and W. bancrofti. Phylogenetic analysis indicated that the ALT-2 consensus sequences formed three clades: the first consisting of B. malayi, the second consisting of W. bancrofti, and the third containing both O. volvulus and L. loa. ALT-2 selection was therefore not predictable by phylogeny or pathology, as the two species parasitizing the eye were selected differently, as were the two species parasitizing the lymphatic system. The most immunogenic regions of L. loa and W. bancrofti ALT-2 sequence as modeled by antigenicity prediction analysis did not correspond with elevated levels of diversifying selection, and were not selected differently than predicted antigenic epitopes in B. malayi and O. volvulus. Measurements of ALT-2 evolvability made by χ2 analysis between alleles that were stable (O. volvulus and B. malayi) and those that were under diversifying selection (W. bancrofti and L. loa) indicated significant (P<0.01) deviations from a normal distribution for both W. bancrofti and L. loa. The relationship between evolvability and selection in L. loa followed a second order polynomial distribution (R2 = 0.89), indicating that the two factors relate to one another in accordance with an additional unknown factor. Taken together, these findings indicate discrete evolutionary drivers acting on ALT-2 of the four organisms examined, and the described variation has implications for design of novel vaccines and diagnostic reagents. Additionally, this represents the first mathematical description of evolvability in a naturally occurring setting.