44 research outputs found
Смерть Пушкина
No full textPushkin’s Death
This essay is an attempt to present some new and original ideas about A. S. Puškin’s duel and death. The prolific existing literature concerning the poet often ignores these two events. The author dwells on the role of N. N. Gončarova, who, according to him, provoked the duel and wished her husband’s death. Although A. S. Puškin has constantly and publicly asserted her innocence, there is one exception. In his poem The Imitation of Dante, the poet severely punishes his wife and her sister (which one ?), but the fact seems to remain ignored by the ‘ Pushkinists’. Further, the essay draws our attention to some nuances of the relationship between A. S. Puškin and V. A. Žukovskij, which was not as cloudless as it is considered to be. The author uses information he has collected in the memoirs of contemporaries (friends as well as ill-wishers), of relatives, in the poet’s correspondence and in such invaluable, important documentary and objective sources as V. Veresaev’s Puškin’s Life, the two-volume edition of Puškin’s Letters, P. E. Ščegolev’s book Puškin’s Duel and Death, the academic edition of the Letters to his wife and, of course, in the poet’s own works.La mort de Puškin
Cet article s’efforce de formuler quelques nouvelles considérations sur le duel et la mort de A. S. Puškin, questions absentes d’une littérature, pourtant abondante, consacrée à Puškin. L’article décrit le rôle de N. N. Gončarova, qui, d’après l’auteur de l’article, provoqua ce duel fatal. Il cite les raisons pour lesquelles celle-ci pouvait vouloir la mort de son mari, bien que Puškin affirma constamment et publiquement qu’elle fut innocente, hormis une seule exception dans un poème l’Imitation de Dante. Ce fait apparemment passa inaperçu ou fut ignoré des spécialistes de Puškin. Puis l’article explicite certaines nuances dans les relations entre A. S. Puškin et V. A. Žukovskij, qui ne furent pas aussi idylliques qu’il est convenu de le considérer. L’auteur a puisé ses informations dans les souvenirs des contemporains (amis comme ennemis), des parents, de la correspondance du poète et d’autres sources essentielles et appréciables par leur objectivité, comme la Vie de Puškin de V. Veresaev, les Lettres de Puškin en deux volumes, l’ouvrage de P. E. Ščegolev le Duel et la Mort de Puškin, l’édition académique des Lettres à sa femme et enfin les oeuvres complètes du poète.Besserman Gregory. Смерть Пушкина. In: Revue des études slaves, tome 81, fascicule 4, 2010. pp. 451-473
a prospective cohort study
Get PDFFunding Information: The members of VIP1 and VIP2 study groups are listed in Additional file 1 and are listed in their individual PubMed records. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.Background: The Clinical Frailty Scale (CFS) is frequently used to measure frailty in critically ill adults. There is wide variation in the approach to analysing the relationship between the CFS score and mortality after admission to the ICU. This study aimed to evaluate the influence of modelling approach on the association between the CFS score and short-term mortality and quantify the prognostic value of frailty in this context. Methods: We analysed data from two multicentre prospective cohort studies which enrolled intensive care unit patients ≥ 80 years old in 26 countries. The primary outcome was mortality within 30-days from admission to the ICU. Logistic regression models for both ICU and 30-day mortality included the CFS score as either a categorical, continuous or dichotomous variable and were adjusted for patient’s age, sex, reason for admission to the ICU, and admission Sequential Organ Failure Assessment score. Results: The median age in the sample of 7487 consecutive patients was 84 years (IQR 81–87). The highest fraction of new prognostic information from frailty in the context of 30-day mortality was observed when the CFS score was treated as either a categorical variable using all original levels of frailty or a nonlinear continuous variable and was equal to 9% using these modelling approaches (p < 0.001). The relationship between the CFS score and mortality was nonlinear (p < 0.01). Conclusion: Knowledge about a patient’s frailty status adds a substantial amount of new prognostic information at the moment of admission to the ICU. Arbitrary simplification of the CFS score into fewer groups than originally intended leads to a loss of information and should be avoided. Trial registration NCT03134807 (VIP1), NCT03370692 (VIP2)publishersversionpublishe
Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study
Get PDFBackground
Early in the pandemic it was suggested that pre-existing use of non-steroidal anti-inflammatory drugs (NSAIDs) could lead to increased disease severity in patients with COVID-19. NSAIDs are an important analgesic, particularly in those with rheumatological disease, and are widely available to the general public without prescription. Evidence from community studies, administrative data, and small studies of hospitalised patients suggest NSAIDs are not associated with poorer COVID-19 outcomes. We aimed to characterise the safety of NSAIDs and identify whether pre-existing NSAID use was associated with increased severity of COVID-19 disease.
Methods
This prospective, multicentre cohort study included patients of any age admitted to hospital with a confirmed or highly suspected SARS-CoV-2 infection leading to COVID-19 between Jan 17 and Aug 10, 2020. The primary outcome was in-hospital mortality, and secondary outcomes were disease severity at presentation, admission to critical care, receipt of invasive ventilation, receipt of non-invasive ventilation, use of supplementary oxygen, and acute kidney injury. NSAID use was required to be within the 2 weeks before hospital admission. We used logistic regression to estimate the effects of NSAIDs and adjust for confounding variables. We used propensity score matching to further estimate effects of NSAIDS while accounting for covariate differences in populations.
Results
Between Jan 17 and Aug 10, 2020, we enrolled 78 674 patients across 255 health-care facilities in England, Scotland, and Wales. 72 179 patients had death outcomes available for matching; 40 406 (56·2%) of 71 915 were men, 31 509 (43·8%) were women. In this cohort, 4211 (5·8%) patients were recorded as taking systemic NSAIDs before admission to hospital. Following propensity score matching, balanced groups of NSAIDs users and NSAIDs non-users were obtained (4205 patients in each group). At hospital admission, we observed no significant differences in severity between exposure groups. After adjusting for explanatory variables, NSAID use was not associated with worse in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35), critical care admission (1·01, 0·87–1·17; p=0·89), requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69), requirement for non-invasive ventilation (1·12, 0·96–1·32; p=0·14), requirement for oxygen (1·00, 0·89–1·12; p=0·97), or occurrence of acute kidney injury (1·08, 0·92–1·26; p=0·33).
Interpretation
NSAID use is not associated with higher mortality or increased severity of COVID-19. Policy makers should consider reviewing issued advice around NSAID prescribing and COVID-19 severity.
Funding
National Institute for Health Research and Medical Research Council
Conditions of membership in the people of God : A study based on Acts 15 and other relevant passages in Acts.
Get PDFImmunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database
Get PDFBackground: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013
Core outcome set for peripheral regional anesthesia research: a systematic review and Delphi study
No full textBackground/importance: There is heterogeneity among the outcomes used in regional anesthesia research. Objective: We aimed to produce a core outcome set for regional anesthesia research. Methods: We conducted a systematic review and Delphi study to develop this core outcome set. A systematic review of the literature from January 2015 to December 2019 was undertaken to generate a long list of potential outcomes to be included in the core outcome set. For each outcome found, the parameters such as the measurement scale, timing and definitions, were compiled. Regional anesthesia experts were then recruited to participate in a three-round electronic modified Delphi process with incremental thresholds to generate a core outcome set. Once the core outcomes were decided, a final Delphi survey and video conference vote was used to reach a consensus on the outcome parameters. Results: Two hundred and six papers were generated following the systematic review, producing a long list of 224 unique outcomes. Twenty-one international regional anesthesia experts participated in the study. Ten core outcomes were selected after three Delphi survey rounds with 13 outcome parameters reaching consensus after a final Delphi survey and video conference. Conclusions: We present the first core outcome set for regional anesthesia derived by international expert consensus. These are proposed not to limit the outcomes examined in future studies, but rather to serve as a minimum core set. If adopted, this may increase the relevance of outcomes being studied, reduce selective reporting bias and increase the availability and suitability of data for meta-analysis in this area. </p
Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity
Get PDFThe combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)
Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study
Get PDFObjective To characterise the clinical features of children and young people admitted to hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to covid-19 (MIS-C). Design Prospective observational cohort study with rapid data gathering and near real time analysis. Setting 260 acute care hospitals in England, Wales, and Scotland between 17th January and 5th June 2020, with a minimal follow-up time of two weeks (to 19th June 2020). Participants 451 children and young people aged less than 19 years admitted to 116 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory-confirmed SARS-CoV-2. Main Outcome Measures Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C. Results Median age was 3.9 years [interquartile range (IQR) 0.3-12.9 years], 36% (162/451) were under 12 months old, and 57% (256/450) were male. 56% (224/401) were White, 12% (49/401) South Asian and 10% (40/401) Black. 43% (195/451) had at least one recorded comorbidity. A muco-enteric cluster of symptoms was identified, closely mirroring the WHO MIS-C criteria. 17% of children (72/431) were admitted to critical care. On multivariable analysis this was associated with age under one month odds ratio 5.05 (95% confidence interval 1.69 to 15.72, p=0.004), age 10 to 14 years OR 3.11 (1.21 to 8.55, p=0.022) and Black ethnicity OR 3.02 (1.30 to 6.84, p=0.008). Three young people died (0.7 %, 3/451) aged 16 to 19 years, all of whom had profound comorbidity. Twelve percent of children (36/303) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Those meeting MIS-C criteria were older, (median age 10.8 years ([IQR 8.4-14.1] vs 2.0 [0.2-12.6]), p<0.001) and more likely to be of non-White ethnicity (70% (23/33) vs 43% (101/237), p=0.005). Children with MIS-C were four times more likely to be admitted to critical care (61% (22/36) vs 15% (40/267, p<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with headache (45% (13/29) vs 11% (19/171), p<0.001), myalgia (39% (11/28) vs 7% (12/170), p<0.001), sore throat (37% (10/27) vs (13% (24/183, p = 0.004) and fatigue (57% (17/30) vs 31% (60/192), p =0.012) than children who did not and to have a platelet count of less than 150 x109/L (30% (10/33) vs 10% (24/232), p=0.004). Conclusions Our data confirms less severe covid-19 in children and young people than in adults and we provide additional evidence for refining the MIS-C case definition. The identification of a muco-enteric symptom cluster also raises the suggestion that MIS-C is the severe end of a spectrum of disease. Study registration ISRCTN6672626
Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study
Get PDFAbstract
Background
Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality.
Methods
Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model.
Results
From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p < 0.001) and had lower driving (12 [8–16] vs 15 [11–17] cmH2O, p < 0.001), plateau (20 [15–23] vs 22 [19–26] cmH2O, p < 0.001) and peak (21 [17–27] vs 26 [20–32] cmH2O, p < 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60–1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16–2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06–1.18], p < 0.001) and tidal volume after day 7 (HR 0.69 [0.52–0.93], p = 0.015) were related to survival.
Conclusions
Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury.
Trial registration Clinicaltrials.gov NCT02010073
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