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CONTEXTE: La pandemie de maladie a coronavirus du syndrome respiratoire aigu severe 2 (SRAS-CoV-2) est associee a une mortalite elevee dans les unites de soins intensifs (USI). Nous avons voulu decrire les caracteristiques cliniques et les issues des patients gravement atteints de la maladie a coronavirus 2019 (COVID-19) en contexte canadien. METHODES: Nous avons procede a l’etude retrospective d’une serie de cas graves d’infection au SRAS-CoV-2 confirmee en laboratoire hospitalises dans l’une des 6 USI du Vancouver metropolitain, en Colombie-Britannique (Canada), entre le 21 fevrier et le 14 avril 2020. Les donnees demographiques, les renseignements sur la prise en charge et les resultats ont ete recueillis a partir des dossiers medicaux, electroniques ou non, des patients. RESULTATS: Entre le 21 fevrier et le 14 avril 2020, 117 patients ont ete admis dans une USI avec un diagnostic confirme de COVID-19. L’âge median etait de 69 ans (ecart interquartile [EI] 60–75 ans); et 38 (32,5 %) etaient des femmes. Au moins une comorbidite etait presente chez 86 patients (73,5 %). La ventilation mecanique a ete necessaire chez 74 patients (63,2 %). La duree de la ventilation mecanique a ete de 13,5 jours (EI 8–22 jours) dans l’ensemble et de 11 jours (II 6–16) chez les patients qui ont recu leur conge de l’USI. Du tocilizumab a ete administre a 4 patients et de l’hydroxychloroquine a 1 patient. En date du 5 mai 2020, 18 patients (15,4 %) etaient decedes, 12 (10,3 %) etaient toujours a l’USI, 16 (13,7 %) avaient obtenu leur conge de l’USI, mais restaient hospitalises, et 71 (60,7 %) avaient pu retourner a la maison. INTERPRETATION: Dans cette etude, la mortalite chez les patients gravement malades de la COVID-19 hospitalises dans une USI a ete moins elevee que chez les patients d’etudes precedentes. Ces resultats donnent a penser que le pronostic des cas graves de COVID-19 pourrait ne pas etre aussi sombre que ce qui avait d’abord ete rapporte.

Background: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. Methods: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. Results: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60–75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8–22) days overall and 11 (IQR 6–16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. Interpretation: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.

Background Trauma-induced coagulopathy contributes to significant morbidity and mortality in patients who experience trauma-related bleeding. This study aimed to synthesize the evidence supporting the efficacy and safety of preemptive and goal-directed fibrinogen concentrate (FC) in the management of trauma-related hemorrhage. Methods PubMed, Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform were systematically searched. All trial designs, except individual case reports, which evaluated the preemptive or goal-directed use of FC for trauma-related bleeding/coagulopathy, in patients older than 16 years, were included in the systematic review. For the included randomized controlled trials comparing FC with control, meta-analysis was performed and a risk-of bias-assessment was completed using the Cochrane Methodology and Preferred Reporting Items Systematic Reviews and Meta-analysis guidelines. Results A total of 2,743 studies were identified; 26 were included in the systematic review, and 5 randomized controlled trials (n = 238) were included in the meta-analysis. For the primary outcome of mortality, there was no statistically significant difference between the groups, with 22% and 23.4% in the FC and comparator arms, respectively (risk ratio, 1.00 [95% confidence interval, 0.39 to 2.56]; p = 0.99). In addition, there was no statistical difference between FC and control in packed red blood cell, fresh frozen plasma, or platelet transfusion requirements, and thromboembolic events. Overall, the quality of evidence was graded as low to moderate because of concerns with risk of bias, imprecision, and inconsistency. Conclusion Further high-quality, adequately powered studies are needed to assess the impact of FC in trauma, with a focus on administration as early as possible from the point of entry into the trauma system of care. Level of evidence Systematic review and Meta-analysis, level II.

Aims Trigger tools are retrospective surveillance methods that can be used to identify adverse drug events (ADEs), unintended and harmful effects of medications, in medical records. Trigger tools are used in quality improvement, public health surveillance and research activities. The objective of the study was to evaluate the performance of trigger tools in identifying ADEs. Methods This study was a sub-study of a prospective cohort study which enrolled adults presenting to one tertiary care emergency department. Clinical pharmacists evaluated patients for ADEs at the point-of-care. Twelve months after the prospective study's completion, the patients' medical records were reviewed using eight different trigger tools. ADEs identified using each trigger tool were compared with events identified at the point-of-care. The primary outcome was the sensitivity of each trigger tool for ADEs. Results Among 1151 patients, 152 (13.2%, 95% confidence intervals (CI) 11.4, 15.3%) were diagnosed with one or more ADEs at the point-of-care. The sensitivity of the trigger tools for detecting ADEs ranged from 2.6% (95% CI 0.7, 6.6%) to 15.8% (95% CI 10.6, 22.8%). Their specificity varied from 99.3% (95% CI 98.6, 99.7) to 100% (95% CI 99.6, 100%). Conclusion The trigger tools examined had poor sensitivity for identifying ADEs in emergency department patients, when applied manually and in retrospect. Reliance on these methods to detect ADEs for quality improvement, surveillance, and research activities is likely to underestimate their occurrence, and may lead to biased estimates.

Calculation of compressed footings settlement is one of the most vital tasks of soil mechanics. The calculation method of layer-by-layer addition, which recommended by current regulations and used in structural engineering practice, is most suitable for determining the settlement of foundations with an area of less than 50 m 2 . The authors prove that it’s possible to apply the one-dimensional problem of soils compression seal theory to the calculation of the settlement of large foundation plates. The proposed method of determining the settlement of large foundation plates makes the calculations simpler. There are examples of comparable calculations using the existing and proposed methods.

Interferon-α (IFN-α) is essential for antiviral immunity, but in the absence of matrix metalloproteinase-12 (MMP-12) or IκBα (encoded by NFKBIA) we show that IFN-α is retained in the cytosol of virus-infected cells and is not secreted. Our findings suggest that activated IκBα mediates the export of IFN-α from virus-infected cells and that the inability of cells in Mmp12(-/-) but not wild-type mice to express IκBα and thus export IFN-α makes coxsackievirus type B3 infection lethal and renders respiratory syncytial virus more pathogenic. We show here that after macrophage secretion, MMP-12 is transported into virus-infected cells. In HeLa cells MMP-12 is also translocated to the nucleus, where it binds to the NFKBIA promoter, driving transcription. We also identified dual-regulated substrates that are repressed both by MMP-12 binding to the substrate's gene exons and by MMP-12-mediated cleavage of the substrate protein itself. Whereas intracellular MMP-12 mediates NFKBIA transcription, leading to IFN-α secretion and host protection, extracellular MMP-12 cleaves off the IFN-α receptor 2 binding site of systemic IFN-α, preventing an unchecked immune response. Consistent with an unexpected role for MMP-12 in clearing systemic IFN-α, treatment of coxsackievirus type B3-infected wild-type mice with a membrane-impermeable MMP-12 inhibitor elevates systemic IFN-α levels and reduces viral replication in pancreas while sparing intracellular MMP-12. These findings suggest that inhibiting extracellular MMP-12 could be a new avenue for the development of antiviral treatments.

6064 Background: Variations in distribution of the surgical workforce may result in differential access to cancer screening and treatment. Our aim was to explore the relationship between county-level surgical specialist density and BrCa and LuCa mortality. Methods: Using data from Area Resource File, US Census and National Cancer Institute, regression models that controlled for cancer incidence, county demographics and socioeconomic factors were constructed to examine the association among a) general surgeon (GS) and radiation oncologist (RO) density with BrCa mortality and b) thoracic surgeon (ThS) and RO density with LuCa mortality. Plastic (PS) and transplant surgeons (TrS) were used as surgical controls as they were not expected to correlate significantly with BrCa or LuCa mortality. Results: A total of 1,557 and 2,044 US counties were analyzed for BrCa and LuCa, respectively: mean incidences were 119 and 75 and death rates were 25 and 59 per 100,000 people, respectively, for BrCa and LuCa. Mean specialist densities were 7.72 (GS), 0.80 (RO), and 0.97 (PS) [for BrCa counties] and 0.55 (ThS), 0.55 (RO), and 0.01 (TrS) [for LuCa counties] per 100,000. When compared to counties with no surgical specialist, those with at least one GS and RO for BrCa and at least one ThS and RO for LuCa were associated with decreased mortality (Table). Increasing the density of GS and RO beyond 9 and 1 per 100,000 did not result in significant reductions in BrCa mortality. Likewise, increasing the density of ThS and RO to above 1 each per 100,000 failed to yield further improvements in LuCa mortality. Counties with more elderly residents also correlated with worse BrCa and LuCa outcomes. Conclusions: The presence of specific surgical specialists is associated with lower BrCa and LuCa mortality. There appears to be a threshold at which point further increase in their density do not contribute to continued improvements in outcomes. Distributing the surgical workforce across all counties will offer population-based improvements in BrCa and LuCa mortality. [Table: see text]