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OBJECTIVES: To estimate the expected value of undertaking a future randomized controlled trial of thresholds used to initiate invasive ventilation compared with usual care in hypoxemic respiratory failure. PERSPECTIVE: Publicly funded healthcare payer. SETTING: Critical care units capable of providing invasive ventilation and unconstrained by resource limitations during usual (nonpandemic) practice. METHODS: We performed a model-based cost-utility estimation with individual-level simulation and value-of-information analysis focused on adults, admitted to critical care, receiving noninvasive oxygen. In the primary scenario, we compared hypothetical threshold A to usual care, where threshold A resulted in increased use of invasive ventilation and improved survival compared with usual care. In the secondary scenario, we compared hypothetical threshold B to usual care, where threshold B resulted in decreased use of invasive ventilation and similar survival compared with usual care. We assumed a willingness-to-pay of 100,000 Canadian dollars (CADs) per quality-adjusted life year. RESULTS: In the primary scenario, threshold A was cost-effective compared with usual care due to improved hospital survival (78.1% vs. 75.1%), despite more use of invasive ventilation (62% vs. 30%) and higher lifetime costs (86,900 vs. 75,500 CAD). In the secondary scenario, threshold B was cost-effective compared with usual care due to similar survival (74.5% vs. 74.6%) with less use of invasive ventilation (20.2% vs. 27.6%) and lower lifetime costs (71,700 vs. 74,700 CAD). Value-of-information analysis showed that the expected value to Canadian society over 10 years of a 400-person randomized trial comparing a threshold for invasive ventilation to usual care in hypoxemic respiratory failure was 1.35 billion CAD or more in both scenarios. CONCLUSIONS: It would be highly valuable to society to identify thresholds that, in comparison to usual care, either increase survival or reduce invasive ventilation without reducing survival.
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Análisis Costo-Beneficio , Ensayos Clínicos Controlados Aleatorios como Asunto , Respiración Artificial , Insuficiencia Respiratoria , Humanos , Respiración Artificial/economía , Análisis Costo-Beneficio/métodos , Insuficiencia Respiratoria/terapia , Insuficiencia Respiratoria/economía , Insuficiencia Respiratoria/mortalidad , Años de Vida Ajustados por Calidad de Vida , Canadá , Unidades de Cuidados Intensivos/economía , AdultoRESUMEN
BACKGROUND: The response of Canada's research community to the COVID-19 pandemic provides a unique opportunity to examine the country's clinical health research ecosystem. We sought to describe patterns of enrolment across Canadian Institutes of Health Research (CIHR)-funded studies on COVID-19. METHODS: We identified COVID-19 studies funded by the CIHR and that enrolled participants from Canadian acute care hospitals between January 2020 and April 2023. We collected information on study-and site-level variables from study leads, site investigators, and public domain sources. We described and evaluated factors associated with cumulative enrolment. RESULTS: We obtained information for 23 out of 26 (88%) eligible CIHR-funded studies (16 randomized controlled trials [RCTs] and 7 cohort studies). The 23 studies were managed by 12 Canadian and 3 international coordinating centres. Of 419 Canadian hospitals, 97 (23%) enrolled a total of 28 973 participants - 3876 in RCTs across 78 hospitals (median cumulative enrolment per hospital 30, interquartile range [IQR] 10-61), and 25 097 in cohort studies across 62 hospitals (median cumulative enrolment per hospital 158, IQR 6-348). Of 78 hospitals recruiting participants in RCTs, 13 (17%) enrolled 50% of all RCT participants, whereas 6 of 62 hospitals (9.7%) recruited 54% of participants in cohort studies. INTERPRETATION: A minority of Canadian hospitals enrolled the majority of participants in CIHR-funded studies on COVID-19. This analysis sheds light on the Canadian health research ecosystem and provides information for multiple key partners to consider ways to realize the full research potential of Canada's health systems.
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Investigación Biomédica , COVID-19 , Humanos , Canadá/epidemiología , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The last national estimates of US ICU physician staffing are 25 years old and lack information about interprofessional teams. RESEARCH QUESTION: How are US adult ICUs currently staffed? STUDY DESIGN AND METHODS: We conducted a cross-sectional survey (May 4, 2022-February 2, 2023) of adult ICU clinicians (targeting nurse/physician leadership) contacted using 2020 American Hospital Association (AHA) database information and, secondarily, through professional organizations. The survey included questions about interprofessional ICU staffing availability and roles at steady state (pre-COVID-19). We linked survey data to hospital data in the AHA database to create weighted national estimates by extrapolating ICU staffing data to nonrespondent hospitals based on hospital characteristics. RESULTS: The cohort consisted of 596 adult ICUs (response rates: AHA contacts: 2.1%; professional organizations: unknown) with geographic diversity and size variability (median, 20 beds; interquartile range, 12-25); most cared for mixed populations (414 [69.5%]), yet medical (55 [9.2%]), surgical (70 [11.7%]), and specialty (57 [9.6%]) ICUs were well represented. A total of 554 (93.0%) had intensivists available, with intensivists covering all patients in 75.6% of these and onsite 24 h/d in one-half (53.3% weekdays; 51.8% weekends). Of all ICUs, 69.8% had physicians-in-training and 77.7% had nurse practitioners/physician assistants. For patients on mechanical ventilation, nurse to patient ratios were 1:2 in 89.6% of ICUs. Clinical pharmacists were available in 92.6%, and respiratory therapists were available in 98.8%. We estimated 85.1% (95% CI, 85.7%-84.5%) of hospitals nationally had ICUs with intensivists, 51.6% (95% CI, 50.6%-52.5%) had physicians-in-training, 72.1% (95% CI, 71.3%-72.9%) had nurse practitioners/physician assistants, 98.5% (95% CI, 98.4%-98.7%) had respiratory therapists, and 86.9% (95% CI, 86.4%-87.4%) had clinical pharmacists. For patients on mechanical ventilation, 86.4% (95% CI, 85.8%-87.0%) used 1:2 nurses/patients. INTERPRETATION: We found that intensivist presence in adult US ICUs has greatly increased over 25 years. Intensivists, respiratory therapists, and clinical pharmacists are commonly available, and each nurse usually provides care for two patients on mechanical ventilation. However, team composition and workload vary.
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BACKGROUND AND OBJECTIVE: Collection of biosamples for translational research studies is vital for understanding biological pathways, discovering disease-related biomarkers, and identifying novel therapeutic targets. However, a lack of infrastructure for sample procurement, processing, storage, and shipping may hinder the ability of clinical research units to effectively engage in translational research. The purpose of this study was to identify the barriers to biosampling-based translational research in the critical care setting in Canada. METHODS: We administered an online survey to members of the Canadian Critical Care Trials Group (CCCTG), the Canadian Critical Care Translational Biology Group (CCCTBG), and the Canadian Critical Care Research Coordinators Group (CCCRCG). The survey focused on participants' personal experience of biosampling research, research infrastructure, motivating factors, and perceived barriers. RESULTS: We received 59 responses from 31 sites, including 6 community intensive care unit (ICU) sites. The overall response rate was 11.3%. The majority of respondents were research coordinators (44%), followed by clinician-investigators (33.8%), graduate students (10.2%), and PhD-investigators (8.5%). Although most (63.8%) respondents reported an interest in participating in translational research, they also reported that their ICUs were currently contributing to a third of the number of translational studies compared to clinical studies. For respondents with experience in participating in translational research studies, the most common barriers were lack of funding, lack of time, and insufficient research staff. For respondents without previous experience, the perceived facilitators were more interest from their research group, improved training/mentorship, increased funding, and better access to laboratory equipment. CONCLUSIONS: Our survey found that the majority of participants were interested in and recognize the value of participating in biosampling-based translational research but lacked funding, time, and research personnel trained in biosampling protocols. Our survey also identified factors that might encourage participation at new sites. Addressing these barriers will be a key step towards increasing translational research capacity across Canada.
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Cuidados Críticos , Investigadores , Investigación Biomédica Traslacional , Humanos , Canadá , Estudios Transversales , Encuestas y Cuestionarios , Masculino , Femenino , Manejo de Especímenes/métodosRESUMEN
Background: Omalizumab is an anti-immunoglobulin E monoclonal antibody used to treat moderate to severe chronic idiopathic urticaria, asthma, and nasal polyps. Recent research suggested that omalizumab may enhance the innate antiviral response and have anti-inflammatory properties. Objective: We aimed to investigate the efficacy and safety of omalizumab in adults hospitalized for coronavirus disease 2019 (COVID-19) pneumonia. Methods: This was a phase II randomized, double blind, placebo-controlled trial comparing omalizumab with placebo (in addition to standard of care) in hospitalized patients with COVID-19. The primary endpoint was the composite of mechanical ventilation and/or death at day 14. Secondary endpoints included all-cause mortality at day 28, time to clinical improvement, and duration of hospitalization. Results: Of 41 patients recruited, 40 were randomized (20 received the study drug and 20 placebo). The median age of the patients was 74 years and 55.0% were male. Omalizumab was associated with a 92.6% posterior probability of a reduction in mechanical ventilation and death on day 14 with an adjusted odds ratio of 0.11 (95% credible interval 0.002-2.05). Omalizumab was also associated with a 75.9% posterior probability of reduced all-cause mortality on day 28 with an adjusted odds ratio of 0.49 (95% credible interval, 0.06-3.90). No statistically significant differences were found for the time to clinical improvement and duration of hospitalization. Numerically fewer adverse events were reported in the omalizumab group and there were no drug-related serious adverse events. Conclusions: These results suggest that omalizumab could prove protective against death and mechanical ventilation in hospitalized patients with COVID-19. This study could also support the development of a phase III trial program investigating the antiviral and anti-inflammatory effect of omalizumab for severe respiratory viral illnesses requiring hospital admission. ClinicalTrials.gov ID: NCT04720612.
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The inaugural Canadian Conferences on Translational Geroscience were held as 2 complementary sessions in October and November 2023. The conferences explored the profound interplay between the biology of aging, social determinants of health, the potential societal impact of geroscience, and the maintenance of health in aging individuals. Although topics such as cellular senescence, molecular and genetic determinants of aging, and prevention of chronic disease were addressed, the conferences went on to emphasize practical applications for enhancing older people's quality of life. This article summarizes the proceeding and underscores the synergy between clinical and fundamental studies. Future directions highlight national and global collaborations and the crucial integration of early-career investigators. This work charts a course for a national framework for continued innovation and advancement in translational geroscience in Canada.
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Geriatría , Investigación Biomédica Traslacional , Humanos , Canadá , Geriatría/tendencias , Envejecimiento/genética , Envejecimiento/fisiología , Calidad de Vida , Anciano , PredicciónRESUMEN
Importance: The COVID-19 pandemic had a profound impact on the delivery of cancer care, but less is known about its association with place of death and delivery of specialized palliative care (SPC) and potential disparities in these outcomes. Objective: To evaluate the association of the COVID-19 pandemic with death at home and SPC delivery at the end of life and to examine whether disparities in socioeconomic status exist for these outcomes. Design, Setting, and Participants: In this cohort study, an interrupted time series analysis was conducted using Ontario Cancer Registry data comprising adult patients aged 18 years or older who died with cancer between the pre-COVID-19 (March 16, 2015, to March 15, 2020) and COVID-19 (March 16, 2020, to March 15, 2021) periods. The data analysis was performed between March and November 2023. Exposure: COVID-19-related hospital restrictions starting March 16, 2020. Main Outcomes and Measures: Outcomes were death at home and SPC delivery at the end of life (last 30 days before death). Socioeconomic status was measured using Ontario Marginalization Index area-based material deprivation quintiles, with quintile 1 (Q1) indicating the least deprivation; Q3, intermediate deprivation; and Q5, the most deprivation. Segmented linear regression was used to estimate monthly trends in outcomes before, at the start of, and in the first year of the COVID-19 pandemic. Results: Of 173â¯915 patients in the study cohort (mean [SD] age, 72.1 [12.5] years; males, 54.1% [95% CI, 53.8%-54.3%]), 83.7% (95% CI, 83.6%-83.9%) died in the pre-COVID-19 period and 16.3% (95% CI, 16.1%-16.4%) died in the COVID-19 period, 54.5% (95% CI, 54.2%-54.7%) died at home during the entire study period, and 57.8% (95% CI, 57.5%-58.0%) received SPC at the end of life. In March 2020, home deaths increased by 8.3% (95% CI, 7.4%-9.1%); however, this increase was less marked in Q5 (6.1%; 95% CI, 4.4%-7.8%) than in Q1 (11.4%; 95% CI, 9.6%-13.2%) and Q3 (10.0%; 95% CI, 9.0%-11.1%). There was a simultaneous decrease of 5.3% (95% CI, -6.3% to -4.4%) in the rate of SPC at the end of life, with no significant difference among quintiles. Patients who received SPC at the end of life (vs no SPC) were more likely to die at home before and during the pandemic. However, there was a larger immediate increase in home deaths among those who received no SPC at the end of life vs those who received SPC (Q1, 17.5% [95% CI, 15.2%-19.8%] vs 7.6% [95% CI, 5.4%-9.7%]; Q3, 12.7% [95% CI, 10.8%-14.5%] vs 9.0% [95% CI, 7.2%-10.7%]). For Q5, the increase in home deaths was significant only for patients who did not receive SPC (13.9% [95% CI, 11.9%-15.8%] vs 1.2% [95% CI, -1.0% to 3.5%]). Conclusions and Relevance: These findings suggest that the COVID-19 pandemic was associated with amplified socioeconomic disparities in death at home and SPC delivery at the end of life. Future research should focus on the mechanisms of these disparities and on developing interventions to ensure equitable and consistent SPC access.
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COVID-19 , Neoplasias , Adulto , Masculino , Humanos , Anciano , Cuidados Paliativos , Estudios de Cohortes , Pandemias , COVID-19/epidemiología , Clase Social , Neoplasias/epidemiología , Neoplasias/terapia , MuerteRESUMEN
RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.
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COVID-19 , Subtipo H1N1 del Virus de la Influenza A , Gripe Humana , Neumonía Bacteriana , Síndrome de Dificultad Respiratoria , Humanos , COVID-19/complicaciones , Gripe Humana/complicaciones , Gripe Humana/terapia , Espectrometría de Masas en Tándem , Cromatografía Liquida , Lisina , Síndrome de Dificultad Respiratoria/complicaciones , Síndrome de Dificultad Respiratoria/terapia , PiruvatosRESUMEN
INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).
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COVID-19 , Infecciones Estafilocócicas , Humanos , SARS-CoV-2 , Consentimiento Informado , Ontario , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Bloodstream infections (BSIs) are associated with significant mortality and morbidity, including multiple organ dysfunction. We explored if delayed adequate antimicrobial treatment for children with BSIs is associated with change in organ dysfunction as measured by PELOD-2 scores. METHODS: We conducted a multicenter, retrospective cohort study of critically ill children <18 years old with BSIs. The primary outcome was change in PELOD-2 score between days 1 (index blood culture) and 5. The exposure variable was delayed administration of adequate antimicrobial therapy by ≥3 h from blood culture collection. We compared PELOD-2 score changes between those who received early and delayed treatment. RESULTS: Among 202 children, the median (interquartile range) time to adequate antimicrobial therapy was 7 (0.8-20.1) hours; 124 (61%) received delayed antimicrobial therapy. Patients who received early and delayed treatment had similar baseline characteristics. There was no significant difference in PELOD-2 score changes from days 1 and 5 between groups (PELOD-2 score difference -0.07, 95% CI -0.92 to 0.79, p = 0.88). CONCLUSIONS: We did not find an association between delayed adequate antimicrobial therapy and PELOD-2 score changes between days 1 and 5 from detection of BSI. PELOD-2 score was not sensitive for clinical effects of delayed antimicrobial treatment. IMPACT: In critically ill children with bloodstream infections, there was no significant change in organ dysfunction as measured by PELOD-2 scores between patients who received adequate antimicrobial therapy within 3 h of their initial positive blood culture and those who started after 3 h. Higher PELOD-2 scores on day 1 were associated with larger differences in PELOD-2 scores between days 1 and 5 from index positive blood cultures. Further study is required to determine if PELOD-2 or alternative measures of organ dysfunction could be used as primary outcome measures in trials of antimicrobial interventions in pediatric critical care research.
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Antiinfecciosos , Insuficiencia Multiorgánica , Niño , Humanos , Adolescente , Insuficiencia Multiorgánica/tratamiento farmacológico , Enfermedad Crítica , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Unidades de Cuidado Intensivo Pediátrico , Estudios Prospectivos , Antiinfecciosos/uso terapéuticoRESUMEN
Many COVID-19 survivors have post-COVID-19 conditions, and females are at a higher risk. We sought to determine (1) how protein levels change from acute to post-COVID-19 conditions, (2) whether females have a plasma protein signature different from that of males, and (3) which biological pathways are associated with COVID-19 when compared to restrictive lung disease. We measured protein levels in 74 patients on the day of admission and at 3 and 6 months after diagnosis. We determined protein concentrations by multiple reaction monitoring (MRM) using a panel of 269 heavy-labeled peptides. The predicted forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO) were measured by routine pulmonary function testing. Proteins associated with six key lipid-related pathways increased from admission to 3 and 6 months; conversely, proteins related to innate immune responses and vasoconstriction-related proteins decreased. Multiple biological functions were regulated differentially between females and males. Concentrations of eight proteins were associated with FVC, %, and they together had c-statistics of 0.751 (CI:0.732-0.779); similarly, concentrations of five proteins had c-statistics of 0.707 (CI:0.676-0.737) for DLCO, %. Lipid biology may drive evolution from acute to post-COVID-19 conditions, while activation of innate immunity and vascular regulation pathways decreased over that period. (ProteomeXchange identifiers: PXD041762, PXD029437).
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COVID-19 , Proteómica , Masculino , Femenino , Humanos , Pulmón , Capacidad Vital , Enfermedad Crónica , LípidosRESUMEN
Background: Patients with nosocomial acquisition of COVID-19 have poor outcomes but have not been included in therapeutic trials to date. Methods: A pragmatic open-label randomized controlled trial of anti-SARS-CoV-2 monoclonal antibodies (mAb) was performed in hospitalized patients with nosocomial COVID-19 infection in acute care hospitals spanning a provincial health care network. Participants within 5 days of first positive test or symptom onset were randomized to standard of care (SOC) plus a single dose intravenous mAb treatment (bamlanivimab or casirivimab/imdevimab) or SOC alone on a 2:1 basis. The primary study endpoint was the need for invasive mechanical ventilation (IMV) or inpatient mortality by day 60 after randomization. Results: Forty-six participants were enrolled from 13 hospitals between February 14 and October 8, 2021: 31 in the mAb and 15 in the SOC arm. IMV or inpatient mortality up to day 60 occurred in 4 (12.9%) participants in the mAb versus 3 in the SOC arm (20.0%), difference of -7.1% (95% CI -22.5 to 13.4, p = 0.67). The study was terminated early due to lack of equipoise as effectiveness of anti-viral therapies and mAb was published in similar high-risk patient populations. Conclusions: The trial was underpowered to detect meaningful differences given its early termination. The study does highlight the feasibility of undertaking trials in this patient population using a pragmatic approach allowing for trial participation and treatment access across a large health care network and may serve as a template for future designs.
Historique: Les patients qui contractent une COVID-19 nosocomiale ont de mauvais résultats cliniques, mais n'ont pas fait partie des études thérapeutiques jusqu'à présent. Méthodologie: Les chercheurs ont mené une étude randomisée et contrôlée ouverte et pragmatique des anticorps monoclonaux (AcM) anti-SRAS-CoV-2 auprès de patients hospitalisés qui ont contracté une COVID-19 nosocomiale dans les hôpitaux de soins aigus d'un réseau de santé provincial. Dans les cinq jours suivant un premier test positif ou l'apparition des symptômes, les participants ont été divisés de manière randomisée entre la norme des soins (NdS) combinée à une monodose de traitement aux AcM par voie intraveineuse (bamlanivimab ou casirivimab-imdevimab) ou la NdS seule sur une base de deux pour un. Le critère d'évaluation primaire de l'étude était la ventilation mécanique invasive (VMI) ou la mortalité en milieu hospitalier le 60e jour après la randomisation. Résultats: Au total, 46 participants de 13 hôpitaux ont été inclus entre le 14 février et le 8 octobre 2021, soit 31 patients du volet des AcM et 15 du volet de la NdS. La VMI ou la mortalité en milieu hospitalier jusqu'au 60e jour a été observée chez quatre participants au volet des AcM (12,9 %) et trois participants du volet de la NdS (20,0 %), soit une différence de −7,1 % (IC à 95 %, −22,5 à 13,4, p = 0,67). L'étude a été interrompue précocement à cause de l'absence d'équilibre clinique, car des données sur l'efficacité des traitements antiviraux et des AcM ont été publiées au sujet de populations semblables de patients à haut risque. Conclusions: L'échantillon à l'étude était insuffisant pour déceler des différences significatives compte tenu de son interruption précoce. Cette recherche fait ressortir la faisabilité d'études auprès de cette population de patients au moyen d'une approche pragmatique pour y inclure des participants et accéder au traitement dans un vaste réseau de soins et pourrait servir de modèle pour concevoir d'autres études.
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INTRODUCTION: Post-acute coronavirus disease 2019 (COVID-19) syndrome (PACS) is a growing concern, with headache being a particularly debilitating symptom with high prevalence. The long-term effects of COVID-19 and post-COVID headache on brain function remain poorly understood, particularly among non-hospitalized individuals. This study focused on the power-law scaling behavior of functional brain dynamics, indexed by the Hurst exponent (H). This measure is suppressed during physiological and psychological distress and was thus hypothesized to be reduced in individuals with post-COVID syndrome, with greatest reductions among those with persistent headache. METHODS: Resting-state blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging data were collected for 57 individuals who had COVID-19 (32 with no headache, 14 with ongoing headache, 11 recovered) and 17 controls who had cold and flu-like symptoms but tested negative for COVID-19. Individuals were assessed an average of 4-5 months after COVID testing, in a cross-sectional, observational study design. RESULTS: No significant differences in H values were found between non-headache COVID-19 and control groups., while those with ongoing headache had significantly reduced H values, and those who had recovered from headache had elevated H values, relative to non-headache groups. Effects were greatest in temporal, sensorimotor, and insular brain regions. Reduced H in these regions was also associated with decreased BOLD activity and local functional connectivity. CONCLUSIONS: These findings provide new insights into the neurophysiological mechanisms that underlie persistent post-COVID headache, with reduced BOLD scaling as a potential biomarker that is specific to this debilitating condition.
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Prueba de COVID-19 , COVID-19 , Humanos , Estudios Transversales , Imagen por Resonancia Magnética/métodos , COVID-19/complicaciones , Encéfalo/fisiología , Cefalea/diagnóstico por imagen , Cefalea/etiologíaRESUMEN
Importance: The COVID-19 pandemic caused large disruptions to health care for hospitalized older adults. The incidence and management of delirium may have been affected by high rates of COVID-19 infection, staffing shortages, overwhelmed hospital capacity, and changes to visitor policies. Objective: To measure changes in rates of delirium and related medication prescribing during the COVID-19 pandemic among hospitalized older adults. Design, Setting, and Participants: This population-based, repeated cross-sectional study used linked databases to measure rates of delirium and related medication prescriptions among adults aged 66 years or older hospitalized before and during the COVID-19 pandemic (January 1, 2017, to March 31, 2022) in Ontario, Canada. Exposure: The first 2 years of the COVID-19 pandemic (March 1, 2020, to March 31, 2022). Main Outcomes and Measures: The main outcomes were weekly rates of delirium per 1000 admitted population and monthly rates of new antipsychotic and benzodiazepine prescriptions per 1000 discharged population. Observed rates were compared with projected rates based on modeling from 3 years before pandemic onset. Results: Among 2â¯128â¯411 hospitalizations of older adults over the 5-year study period (50.7% female; mean [SD] age, 78.9 [8.3] years), absolute rates of delirium increased from 35.9 per 1000 admitted population during the prepandemic period to 41.5 per 1000 admitted population throughout the pandemic. The adjusted rate ratio (ARR) of delirium during the pandemic compared with the projected rate was 1.15 (95% CI, 1.11-1.19). Monthly rates of new antipsychotic prescriptions increased from 6.9 to 8.8 per 1000 discharged population and new benzodiazepine prescriptions from 4.4 to 6.0 per 1000 discharged population and were significantly higher during the pandemic compared with projected rates (antipsychotics: ARR, 1.28; 95% CI, 1.19-1.38; benzodiazepines: ARR, 1.37; 95% CI, 1.20-1.57). Rates were highest during pandemic waves 1 (March to June 2020), 3 (March to June 2021), and 5 (December 2021 to February 2022) and remained elevated above projected levels throughout the first 2 years of the pandemic. Conclusions and Relevance: In this repeated cross-sectional study of hospitalized older adults, there was a temporal association between COVID-19 pandemic onset and significant increases in rates of delirium in the hospital and new antipsychotic and benzodiazepine prescriptions after hospital discharge. Rates remained elevated over 2 years. Pandemic-related changes such as visitor restrictions, staff shortages, isolation practices, and reduced staff time at the bedside may have contributed to these trends.
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Antipsicóticos , COVID-19 , Delirio , Humanos , Femenino , Anciano , Masculino , Benzodiazepinas/uso terapéutico , COVID-19/epidemiología , Antipsicóticos/uso terapéutico , Pandemias , Estudios Transversales , Ontario/epidemiología , Delirio/tratamiento farmacológico , Delirio/epidemiologíaRESUMEN
Background: Traditionally, bacterial infections have been treated with fixed-duration antibiotic courses; however, some have advocated for individualized durations. It is not known which approach currently predominates. Methods: We conducted a multinational clinical practice survey asking prescribers their approach to treating skin and soft tissue infection (SSTI), community-acquired pneumonia (CAP), pyelonephritis, cholangitis and bloodstream infection (BSI) of an unknown source. The primary outcome was self-reported treatment approach as being fully fixed duration, fixed minimum, fixed maximum, fixed minimum and maximum, or fully individualized durations. Secondary questions explored factors influencing duration of therapy. Multivariable logistic regression with generalized estimating equations was used to examine predictors of use of fully fixed durations. Results: Among 221 respondents, 170 (76.9%) completed the full survey; infectious diseases physicians accounted for 60.6%. Use of a fully fixed duration was least common for SSTI (8.5%) and more common for CAP (28.3%), BSI (29.9%), cholangitis (35.7%) and pyelonephritis (36.3%). Fully individualized therapy, with no fixed minimum or maximum, was used by only a minority: CAP (4.9%), pyelonephritis (5.0%), cholangitis (9.9%), BSI (13.6%) and SSTI (19.5%). In multivariable analyses, a fully fixed duration approach was more common among Canadian respondents [adjusted OR (aOR) 1.76 (95% CI 1.12-2.76)] and for CAP (aOR 4.25, 95% CI 2.53-7.13), cholangitis (aOR 6.01, 95% CI 3.49-10.36), pyelonephritis (aOR 6.08, 95% CI 3.56-10.39) and BSI (aOR 4.49, 95% CI 2.50-8.09) compared with SSTI. Conclusions: There is extensive practice heterogeneity in fixed versus individualized treatment; clinical trials would be helpful to compare these approaches.
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BACKGROUND: Omicron is the current predominant variant of concern of SARS-CoV-2. We hypothesized that vaccination alters outcomes of patients hospitalized with COVID-19 during the Omicron wave and that these patients have different characteristics and outcomes than in previous waves. METHODS: This is a substudy of the Host Response Mediators in Coronavirus (COVID-19) Infection (ARBs CORONA I) trial, which included adults admitted to hospital with acute COVID-19 up to July 2022 from 9 hospitals in British Columbia, Ontario and Quebec. We excluded emergency department visits without hospital admission, readmissions and admissions for another reason. Using adjusted regression analysis, we compared mortality and organ dysfunction between vaccinated (≥ 2 doses) and unvaccinated patients during the Omicron wave, as well as between all patients in the Omicron and first 3 waves of the COVID-19 pandemic. RESULTS: During the Omicron wave, 28-day mortality was significantly lower in vaccinated (n = 19/237) than unvaccinated hospitalized patients (n = 12/127) (adjusted odds ratio [OR] 0.36, 95% confidence interval [CI] 0.15-0.89); vaccinated patients had lower risk of admission to the intensive care unit, invasive ventilation and acute respiratory distress syndrome and shorter hospital length of stay. Patients hospitalized during the Omicron wave had more comorbidities than in previous waves, and lower 28-day mortality than in waves 1 and 2 (adjusted OR 0.38, 95% CI 0.24-0.59; and 0.42, 95% CI 0.26-0.65) but not wave 3 (adjusted OR 0.81, 95% CI 0.43-1.51) and had less organ dysfunction than in the first 2 waves. INTERPRETATION: Patients who were at least double vaccinated had lower mortality than unvaccinated patients hospitalized during the Omicron wave. Patients hospitalized during the Omicron wave had more chronic disease and lower mortality than in the first 2 waves, but not wave 3. Changes in vaccination, treatments and predominant SARS-CoV-2 variant may have decreased mortality in patients hospitalized during the Omicron wave.
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Importance: Recognizing and preventing patient deterioration is important for hospital safety. Objective: To investigate whether critical illness events (in-hospital death or intensive care unit [ICU] transfer) are associated with greater risk of subsequent critical illness events for other patients on the same medical ward. Design, Setting, and Participants: Retrospective cohort study in 5 hospitals in Toronto, Canada, including 118â¯529 hospitalizations. Patients were admitted to general internal medicine wards between April 1, 2010, and October 31, 2017. Data were analyzed between January 1, 2020, and April 10, 2023. Exposures: Critical illness events (in-hospital death or ICU transfer). Main Outcomes and Measures: The primary outcome was the composite of in-hospital death or ICU transfer. The association between critical illness events on the same ward across 6-hour intervals was studied using discrete-time survival analysis, adjusting for patient and situational factors. The association between critical illness events on different comparable wards in the same hospital was measured as a negative control. Results: The cohort included 118â¯529 hospitalizations (median age, 72 years [IQR, 56-83 years]; 50.7% male). Death or ICU transfer occurred in 8785 hospitalizations (7.4%). Patients were more likely to experience the primary outcome after exposure to 1 prior event (adjusted odds ratio [AOR], 1.39; 95% CI, 1.30-1.48) and more than 1 prior event (AOR, 1.49; 95% CI, 1.33-1.68) in the prior 6-hour interval compared with no exposure. The exposure was associated with increased odds of subsequent ICU transfer (1 event: AOR, 1.67; 95% CI, 1.54-1.81; >1 event: AOR, 2.05; 95% CI, 1.79-2.36) but not death alone (1 event: AOR, 1.08; 95% CI, 0.97-1.19; >1 event: AOR, 0.88; 95% CI, 0.71-1.09). There was no significant association between critical illness events on different wards within the same hospital. Conclusions and Relevance: Findings of this cohort study suggest that patients are more likely to be transferred to the ICU in the hours after another patient's critical illness event on the same ward. This phenomenon could have several explanations, including increased recognition of critical illness and preemptive ICU transfers, resource diversion to the first event, or fluctuations in ward or ICU capacity. Patient safety may be improved by better understanding the clustering of ICU transfers on medical wards.
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Enfermedad Crítica , Unidades de Cuidados Intensivos , Humanos , Masculino , Anciano , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Enfermedad Crítica/terapia , Enfermedad Crítica/mortalidad , Mortalidad Hospitalaria , Hospitales , Análisis por ConglomeradosRESUMEN
BACKGROUND: Randomized controlled trials (RCTs) provide essential evidence to inform practice, but the many necessary steps result in lengthy times to initiation, which is problematic in the case of rapidly emerging infections such as COVID-19. This study aimed to describe the start-up timelines for the Canadian Treatments for COVID-19 (CATCO) RCT. METHODS: We surveyed hospitals participating in CATCO and ethics submission sites using a structured data abstraction form. We measured durations from protocol receipt to site activation and to first patient enrolment, as well as durations of administrative processes, including research ethics board (REB) approval, contract execution and lead times between approvals to site activation. RESULTS: All 48 hospitals (26 academic, 22 community) and 4 ethics submission sites responded. The median time from protocol receipt to trial initiation was 111 days (interquartile range [IQR] 39-189 d, range 15-412 d). The median time between protocol receipt and REB submission was 41 days (IQR 10-56 d, range 4-195 d), from REB submission to approval, 4.5 days (IQR 1-12 d, range 0-169 d), from REB approval to site activation, 35 days (IQR 22-103 d, range 0-169 d), from protocol receipt to contract submission, 42 days (IQR 20-51 d, range 4-237 d), from contract submission to full contract execution, 24 days (IQR 15-58 d, range 5-164 d) and from contract execution to site activation, 10 days (IQR 6-27 d, range 0-216 d). Processes took longer in community hospitals than in academic hospitals. INTERPRETATION: The time required to initiate RCTs in Canada was lengthy and varied among sites. Adoption of template clinical trial agreements, greater harmonization or central coordination of ethics submissions, and long-term funding of platform trials that engage academic and community hospitals are potential solutions to improve trial start-up efficiency.
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COVID-19 , Humanos , COVID-19/epidemiología , Canadá/epidemiología , Factores de Tiempo , HospitalesRESUMEN
BACKGROUND: While simple Audit & Feedback (A&F) has shown modest effectiveness in reducing low-value care, there is a knowledge gap on the effectiveness of multifaceted interventions to support de-implementation efforts. Given the need to make rapid decisions in a context of multiple diagnostic and therapeutic options, trauma is a high-risk setting for low-value care. Furthermore, trauma systems are a favorable setting for de-implementation interventions as they have quality improvement teams with medical leadership, routinely collected clinical data, and performance-linked to accreditation. We aim to evaluate the effectiveness of a multifaceted intervention for reducing low-value clinical practices in acute adult trauma care. METHODS: We will conduct a pragmatic cluster randomized controlled trial (cRCT) embedded in a Canadian provincial quality assurance program. Level I-III trauma centers (n = 30) will be randomized (1:1) to receive simple A&F (control) or a multifaceted intervention (intervention). The intervention, developed using extensive background work and UK Medical Research Council guidelines, includes an A&F report, educational meetings, and facilitation visits. The primary outcome will be the use of low-value initial diagnostic imaging, assessed at the patient level using routinely collected trauma registry data. Secondary outcomes will be low-value specialist consultation, low-value repeat imaging after a patient transfer, unintended consequences, determinants for successful implementation, and incremental cost-effectiveness ratios. DISCUSSION: On completion of the cRCT, if the intervention is effective and cost-effective, the multifaceted intervention will be integrated into trauma systems across Canada. Medium and long-term benefits may include a reduction in adverse events for patients and an increase in resource availability. The proposed intervention targets a problem identified by stakeholders, is based on extensive background work, was developed using a partnership approach, is low-cost, and is linked to accreditation. There will be no attrition, identification, or recruitment bias as the intervention is mandatory in line with trauma center designation requirements, and all outcomes will be assessed with routinely collected data. However, investigators cannot be blinded to group allocation and there is a possibility of contamination bias that will be minimized by conducting intervention refinement only with participants in the intervention arm. TRIAL REGISTRATION: This protocol has been registered on ClinicalTrials.gov (February 24, 2023, # NCT05744154 ).