Outcomes of critically ill older adults with COVID-19: a multicentre retrospective cohort study.

PURPOSE: Older adults with COVID-19 have a high prevalence of complications and mortality during hospitalization. Given the large proportion of older adults requiring admission to an intensive care unit (ICU), we aimed to describe the management and outcomes of older adults with COVID-19 requiring ICU care and identify predictors of hospital mortality. METHODS: We included consecutive patients ≥ 65 yr of age who were admitted between 11 March 2020 and 30 June 2021 to one of five Toronto (ON, Canada) ICUs with a primary diagnosis of SARS-CoV-2 infection in a retrospective cohort study. Patient characteristics, ICU treatment, and outcomes were recorded. We used multivariable logistic regression to identify predictors of in-hospital mortality. RESULTS: Of the 273 patients, the median [interquartile range] age was 74 [69-80] yr, 104 (38.1%) were female, and 164 (60.1%) required invasive mechanical ventilation. One hundred and forty-two patients (52.0%) survived their hospital stay. Compared with survivors, nonsurvivors were older (74 [70-82] yr vs 73 [68-78] yr; P = 0.03), and a smaller proportion was female (39/131, 29.8% vs 65/142, 45.8%; P = 0.01). Patients had long hospital (19 [11-35] days) and ICU (9 [5-22] days) stays, with no significant differences in ICU length of stay or duration of invasive mechanical ventilation between the two groups. Higher APACHE II score, increasing age, and the need for organ support were independently associated with higher in-hospital mortality while female sex was associated with lower mortality. CONCLUSIONS: Older critically ill COVID-19 patients had long ICU and hospital stays, and approximately half died in hospital. Further research is needed to identify individuals who will benefit most from an ICU admission and to evaluate posthospitalization outcomes.

RéSUMé: OBJECTIF: Les personnes âgées atteintes de la COVID-19 ont une prévalence élevée de complications et de mortalité pendant l'hospitalisation. Compte tenu de la forte proportion de personnes âgées nécessitant une admission dans une unité de soins intensifs (USI), nous avons cherché à décrire la prise en charge et les devenirs des personnes âgées atteintes de COVID-19 nécessitant des soins intensifs et à identifier les prédicteurs de mortalité hospitalière. MéTHODE: Nous avons inclus des patient·es consécutif·ves âgé·es de ≥ 65 ans admis·es entre le 11 mars 2020 et le 30 juin 2021 dans l'une des cinq unités de soins intensifs de Toronto (ON, Canada) avec un diagnostic primaire d'infection par le SRAS-CoV-2 dans une étude de cohorte rétrospective. Les caractéristiques des patient·es, le traitement en USI et les devenirs ont été enregistrés. Nous avons utilisé une régression logistique multivariable pour identifier les prédicteurs de mortalité hospitalière. RéSULTATS: Parmi les 273 patient·es, l'âge médian [écart interquartile] était de 74 [69-80] ans, 104 (38,1 %) étaient des femmes et 164 (60,1 %) ont nécessité une ventilation mécanique invasive. Cent quarante-deux personnes (52,0 %) ont survécu à leur séjour à l'hôpital. Comparativement aux personnes survivantes, les personnes qui n'ont pas survécu étaient plus âgées (74 [70-82] ans vs 73 [68­78] ans; P = 0,03), et une plus faible proportion était de sexe féminin (39/131, 29,8 % vs 65/142, 45,8 %; P = 0,01). Les séjours des patient·es à l'hôpital (19 [11-35] jours) et à l'USI (9 [5-22] jours) étaient longs, sans différence significative dans la durée du séjour en USI ou la durée de la ventilation mécanique invasive entre les deux groupes. Un score APACHE II plus élevé, un âge plus avancé et le besoin de mesures de soutien d'organes étaient indépendamment associés à une mortalité plus élevée à l'hôpital, tandis que le sexe féminin était associé à une mortalité plus faible. CONCLUSION : Les personnes plus âgées gravement malades atteintes de la COVID-19 ont eu de longs séjours en soins intensifs et à l'hôpital, et environ la moitié sont décédées à l'hôpital. D'autres recherches sont nécessaires pour identifier les personnes qui bénéficieraient le plus d'une admission à l'USI et pour évaluer les devenirs post-hospitalisation.

Vehicle effects on human stratum corneum absorption and skin penetration.

This study evaluated the effects of three vehicles-ethanol (EtOH), isopropyl alcohol (IPA), and isopropyl myristate (IPM)-on stratum corneum (SC) absorption and diffusion of the [14C]-model compounds benzoic acid and butenafine hydrochloride to better understand the transport pathways of chemicals passing through and resident in SC. Following application of topical formulations to human dermatomed skin for 30 min, penetration flux was observed for 24 h post dosing, using an in vitro flow-through skin diffusion system. Skin absorption and penetration was compared to the chemical-SC (intact, delipidized, or SC lipid film) binding levels. A significant vehicle effect was observed for chemical skin penetration and SC absorption. IPA resulted in the greatest levels of intact SC/SC lipid absorption, skin penetration, and total skin absorption/penetration of benzoic acid, followed by IPM and EtOH, respectively. For intact SC absorption and total skin absorption/penetration of butenafine, the vehicle that demonstrated the highest level of sorption/penetration was EtOH, followed by IPA and IPM, respectively. The percent doses of butenafine that were absorbed in SC lipid film and penetrated through skin in 24 h were greatest for IPA, followed by EtOH and IPM, respectively. The vehicle effect was consistent between intact SC absorption and total chemical skin absorption and penetration, as well as SC lipid absorption and chemical penetration through skin, suggesting intercellular transport as a main pathway of skin penetration for model chemicals. These results suggest the potential to predict vehicle effects on skin permeability with simple SC absorption assays. As decontamination was applied 30 min after chemical exposure, significant vehicle effects on chemical SC partitioning and percutaneous penetration also suggest that skin decontamination efficiency is vehicle dependent, and an effective decontamination method should act on chemical solutes in the lipid domain.

The double-edged scalpel: Experiences and perceptions of pregnancy and parenthood during Canadian surgical residency training.

INTRODUCTION: Only 34% of Canadian surgeons in 2022 were female. The protracted length of surgical residency training, concerns regarding infertility, and increased rates of obstetrical complications have been shown to contribute to the disproportionate lack of females in surgical specialties. METHODS: A novel online survey was sent to all surgical residents in Canada. Respondents were asked about perceptions of pregnancy and parenthood during surgical training, and parents were asked about parental leave, accommodations they received, and pregnancy complications. Chi squared tests were used to compare opinions of male and female residents. RESULTS: A total of 272/2,419 (11.2%) responses were obtained, with a high response from females (61.8%) and orthopaedic residents (29.0%). There were 56 women reporting 76 pregnancy events during training, 62.5% of which had complications. Notably, 27.3% of men and 86.7% of women 'agreed' or 'strongly agreed' that surgeons have higher pregnancy complication rates than the general population (p<0.001). Men were much less likely to believe that pregnant residents should be offered modified duties (74.2% of men, 90.0% of women, p = 0.003). Women were much more likely to experience significant stigma or bias due to their status as a parent (43% of women, 0% of men, p<0.001). Women reported negative comments from others at a higher rate (58.5% of women, 40.7% of men, p = 0.013). Women believe there is negative stigma attached to being pregnant during training (62.7% of women, 42.7% of men, p = 0.01). The limitations of our study include a small sample size and response bias. CONCLUSION: Challenges and negative perceptions exist around pregnancy and parenthood in surgical residency, which disproportionately affect women trainees.

Characterization of axial and proximal histidine mutations of the decaheme cytochrome MtrA from Shewanella sp. strain ANA-3 and implications for the electron transport system.

Extracellular respiration of solid-phase electron acceptors in some microorganisms requires a complex chain of multiheme c-type cytochromes that span the inner and outer membranes. In Shewanella species, MtrA, an ~35-kDa periplasmic decaheme c-type cytochrome, is an essential component for extracellular respiration of iron(III). The exact mechanism of electron transport has not yet been resolved, but the arrangement of the polypeptide chain may have a strong influence on the capability of the MtrA cytochrome to transport electrons. The iron hemes of MtrA are bound to its polypeptide chain via proximal (CXXCH) and distal histidine residues. In this study, we show the effects of mutating histidine residues of MtrA to arginine on protein expression and extracellular respiration using Shewanella sp. strain ANA-3 as a model organism. Individual mutations to six out of nine proximal histidines in CXXCH of MtrA led to decreased protein expression. However, distal histidine mutations resulted in various degrees of protein expression. In addition, the effects of histidine mutations on extracellular respiration were tested using ferrihydrite and current production in microbial fuel cells. These results show that proximal histidine mutants were unable to reduce ferrihydrite. Mutations to the distal histidine residues resulted in various degrees of ferrihydrite reduction. These findings indicate that mutations to the proximal histidine residues affect MtrA expression, leading to loss of extracellular respiration ability. In contrast, mutations to the distal histidine residues are less detrimental to protein expression, and extracellular respiration can proceed.

Direct molecule-specific glucose detection by Raman spectroscopy based on photonic crystal fiber.

This paper reports the first step toward the development of a glucose biosensor based on Raman spectroscopy and a photonic crystal fiber (PCF) probe. Historically, it has been very challenging to detect glucose directly by Raman spectroscopy due to its inherently small Raman scattering cross-section. In this work, we report the first quantitative glucose Raman detection in the physiological concentration range (0-25 mM) with a low laser power (2 mW), a short integration time (30 s), and an extremely small sampling volume (~50 nL) using the highly sensitive liquid-filled PCF probe. As a proof of concept, we also demonstrate the molecular specificity of this technique in the presence of a competing sugar, such as fructose. High sensitivity, flexibility, reproducibility, low cost, small sampling volume, and in situ remote sensing capability make PCF a very powerful platform for potential glucose detection based on Raman spectroscopy.

The triponderal mass index as a measure of adiposity in pediatric survivors of acute lymphoblastic leukemia: a cross-sectional study.

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Treatments of ALL predispose survivors to obesity, which increases the risk of cardiovascular disease and diabetes. The hallmark of obesity is excess fat mass, and adiposity is a superior predictor of cardiometabolic risk when compared to Body Mass Index (BMI), yet clinical measures of adiposity in children are lacking. The Tri-Ponderal Mass Index (TMI) (kg/m3) is a more accurate adiposity measure compared to BMI z-score in the general pediatric population. This cross-sectional study aimed to validate TMI as an adiposity measure against DEXA scan-derived adiposity, and to compare it to BMI z-score, in pediatric ALL survivors. This study was a retrospective chart review of pediatric ALL survivors diagnosed between 2004 and 2015 at McMaster Children's Hospital, a tertiary pediatric center in Ontario, Canada. One hundred and thirteen patients (Female n = 55, 48.70%) were included, and adiposity was measured using DEXA scans. Exploratory partial correlations and linear regression analyses were adjusted for age, sex, ethnicity, and ALL risk status. Both TMI and BMI z-score correlated with the DEXA-measured fat mass percentage (FM%) (partial correlation TMI versus FM% r = 0.56; p value < 0.0001; BMI z-score versus FM% r = 0.55; p value < 0.0001). In regression analyses, the association of TMI was not inferior to BMI z-score in assessing adiposity (TMI versus FM% estimated unstandardized B 0.80, 95% CI 0.56, 1.02; p value < 0.0001; BMI z-score versus FM% (unstandardized B 0.37, 95% CI 0.26, 0.49; p value < 0.0001). The TMI is a useful clinical adiposity-specific measure in survivors of pediatric ALL.

Mortality in hospitalized older adults with COVID-19 during three waves: A multicenter retrospective cohort study.

Background: The waves of COVID-19 infections in Ontario, Canada, were marked by differences in patient characteristics and treatment. Our objectives were to (i) describe patient characteristics, treatment, and outcomes of hospitalized older adults with COVID-19 between waves 1, 2, and 3, (ii) determine if there was an improvement in in-hospital mortality in waves 2 and 3 after adjusting for covariates. Methods: This retrospective cohort study was done in five acute care hospitals in Toronto, Ontario. Consecutive hospitalized older adults aged ≥65 years with confirmed COVID-19 infection were included. Wave 1 extended from March 11 to July 31, 2020, wave 2 from August 1, 2020 to February 20, 2021, and wave 3 from February 21 to June 30, 2021. Patient characteristics and outcomes were abstracted from charts. A logistic regression model was used to determine the association between COVID-19 and in-hospital mortality in waves 2 and 3 compared with wave 1. Results: Of the 1671 patients admitted to acute care, 297 (17.8%) were admitted in wave 1, 751 (44.9%) in wave 2, and 623 (37.3%) in wave 3. The median age of our cohort was 77.0 years (interquartile range: 71.0-85.0) and 775 (46.4%) were female. The prevalence of frailty declined in progressive waves. The use of dexamethasone, remdesivir, and tocilizumab was significantly higher in waves 2 and 3 compared with wave 1. In the unadjusted analysis, in-hospital mortality was unchanged between waves 1 and 2, but it was lower in wave 3 (18.3% vs. 27.4% in wave 1). After adjustment, in-hospital mortality was unchanged in waves 2 and 3 compared with wave 1. Conclusion: In-hospital mortality in hospitalized older adults with COVID-19 was similar between waves 1 and 3. Further research should be done to determine if COVID-19 therapies have similar benefits for older adults compared with younger adults.

Characteristics, treatment and delirium incidence of older adults hospitalized with COVID-19: a multicentre retrospective cohort study.

BACKGROUND: The COVID-19 pandemic has affected older adults disproportionately, and delirium is a concerning consequence; however, the relationship between delirium and corticosteroid use is uncertain. The objective of the present study was to describe patient characteristics, treatments and outcomes among older adults hospitalized with COVID-19, with a focus on dexamethasone use and delirium incidence. METHODS: We completed this retrospective cohort study at 7 sites (including acute care, rehabilitation and long-term care settings) in Toronto, Ontario, Canada. We included adults aged 65 years or older, consecutively hospitalized with confirmed SARS-CoV-2 infection, between Mar. 11, 2020, and Apr. 30, 2021. We abstracted patient characteristics and outcomes from charts and analyzed them descriptively. We used a logistic regression model to determine the association between dexamethasone use and delirium incidence. RESULTS: During the study period, 927 patients were admitted to the acute care hospitals with COVID-19. Patients' median age was 79.0 years (interquartile range [IQR] 72.0-87.0), and 417 (45.0%) were female. Most patients were frail (61.9%), based on a Clinical Frailty Scale score of 5 or greater. The prevalence of delirium was 53.6%, and the incidence was 33.1%. Use of restraints was documented in 20.4% of patients. In rehabilitation and long-term care settings (n = 115), patients' median age was 86.0 years (IQR 78.5-91.0), 72 (62.6%) were female and delirium occurred in 17 patients (14.8%). In patients admitted to acute care during wave 2 of the pandemic (Aug. 1, 2020, to Feb. 20, 2021), dexamethasone use had a nonsignificant association with delirium incidence (adjusted odds ratio 1.38, 95% confidence interval 0.77-2.50). Overall, in-hospital death occurred in 262 (28.4%) patients in acute care settings and 28 (24.3%) patients in rehabilitation or long-term care settings. INTERPRETATION: In-hospital death, delirium and use of restraints were common in older adults admitted to hospital with COVID-19. Further research should be directed to improving the quality of care for this population with known vulnerabilities during continued waves of the COVID-19 pandemic.