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Mortalität von mit Ruxolitinib auf Intensivstation behandelten Coronavirus-Krankheit-2019 Erkrankten – eine retrospektive Datenanalyse
No full textIn 2019 the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated disease coronavirus disease-2019 (Covid-19) emerged in China leading to a global health crisis. A significant challenge was the treatment of the acute respiratory distress syndrome (ARDS), a condition associated with the severe form of the disease. A cytokine storm, an overshooting reaction of the immune system, was identified as part of its underlying pathomechanism. Ruxolitinib, a drug that has been successfully used to treat conditions associated with an overactive immune response, has been demonstrated to inhibit the januskinase/signal transducers and activators of transcription (JAK/STAT) pathway, an important pathway in cytokine regulation. Consequently, Ruxolitinib has been trialled in a variety of studies investigating potential treatment options for coronavirus disease 2019.
This study provides an overview of Ruxolitinib therapy in the context of coronavirus disease-2019 in a cohort of patients with severe disease who were primarily invasively ventilated. Data from 137 adult patients (mean age 64 years, standard deviation 11.5, 70 % male) diagnosed with coronavirus disease-2019, who were treated on intensive care units at Klinikum Kassel between February 2020 and March 2021 were retrospectively analysed. Patients who received only low flow oxygen/room air were excluded. Patients were split into two groups. The treatment group (n = 67) received Ruxolitinib for a minimum of three days, whereas the control group (n = 70) received standard of care only. The primary objective was to analyse mortality and survival rates. The results were compared between both groups. Secondary outcomes included the length of intensive care/hospital stay, the impact of Ruxolitinib on the duration of invasive ventilation and the progression of pro-inflammatory markers during the treatment with Ruxolitinib among others.
The in-hospital mortality rate for the treatment group was 47.76 % (32/67), while the equivalent mortality rate for the control group was 41.43 % (29/70). A subgroup analysis of patients that were treated with Ruxolitinib and veno-venous extracorporeal membrane oxygenation (vv ECMO) (n = 42) revealed a mortality rate of 69.05 %. In the same group without extracorporeal membrane oxygenation, the mortality rate was 12 %. The log-rank test demonstrated a statistically significant survival difference between the two groups
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(χ² = 12.7 p<0.001). The median estimated survival in the treatment group was 27 days, in contrast to 15 days in the control group. The hazard ratio for death was elevated in invasively ventilated patients (hazard ratio 3.7, 95 % confidence interval 1.54-8.88; p=0.003). None of the non-invasively ventilated patients died under the Ruxolitinib therapy. Ruxolitinib was unable to shorten the median time spent on intensive care unit (treatment group 18 days (interquartile range 13), vs. control group 8 days (interquartile range 7.75); p<0.001) or the length of hospitalisation, compared to the control group. The median duration of invasive ventilation was longer in the Ruxolitinib group than in the control group (treatment group 20.5 days (interquartile range 18) vs. control group 6.5 days (interquartile range 8.25); p<0.001). A downward trend was observed for Interleukin-6 and C-reactive protein. No signs of toxicity were identified under the therapy with Ruxolitinib.
The present study demonstrates that Ruxolitinib was unable to improve mortality in patients with severe organ dysfunction and veno-venous extracorporeal membrane oxygenation. However, it suggests the necessity for further investigation into the effect of Ruxolitinib in patients with severe disease lacking extracorporeal membrane support. Findings confirm recent investigations on the impact of ventilation on mortality. The absence of death in patients receiving Ruxolitinib and non-invasive ventilation, is consistent with previous research and reinforces the concept of a limited time frame for Ruxolitinib administration. Previous research had indicated a reduction in mortality among invasively ventilated patients undergoing Ruxolitinib therapy; however, this study was unable to confirm these findings. The aforementioned results concerning pro-inflammatory markers are in accordance with recent findings in the literature. Although limited due to the retrospective study design, this study analysed a relatively large cohort of patients treated with Ruxolitinib and offers the opportunity for subgroup analysis. Due to the small number of cases in the subgroup, the reduction in mortality described, can only be seen as a trend. The analysis of the current data suggests that the administration of Ruxolitinib in the described setting must be critically discussed. However, to come to a definitive conclusion, further, at best prospective research is required.Im Jahr 2019 wurde in China das neue Coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) und die daraus resultierende Erkrankung Coronavirus-Krankheit-2019 (Covid-19) nachgewiesen und führte zu einer globalen Gesundheitskrise. Als besonders große Herausforderung stellte sich die Manifestation in Form des akuten Atemnotsyndroms (englisch: acute respiratory distress syndrome (ARDS)) heraus. Als Pathomechanismus konnte eine überschießende Reaktion des Immunsystems, ein sogenannter Zytokinsturm, identifiziert werden. Ruxolitinib, ein Inhibitor des Zytokin regulierenden januskinase/signal transducers and activators of transcription (JAK/STAT) Signalwegs wird erfolgreich zur Behandlung von Erkrankungen mit überschießender Immunreaktion eingesetzt. Folglich wurde Ruxolitinib unteranderem Bestandteil verschiedener, die Behandlungsmöglichkeiten der Coronavirus-Krankheit-2019 erforschenden, Studien.
Diese Studie gibt einen Überblick über die Ruxolitinib-Therapie als Behandlungsansatz der Coronavirus-Erkrankung-2019 bei schwer erkrankten, zumeist invasiv beatmeten Patienten. In der vorliegenden Arbeit wurden die Daten von 137 mit Coronavirus-2019 diagnostizierten erwachsenen Patienten (Altersdurschnitt 64 Jahre, Standardabweichung 11,5, 70 % männlich) retrospektiv analysiert. Die Kohorte wurde zwischen Februar 2020 und März 2021 auf Intensivstationen des Klinikums Kassel behandelt. Patienten ohne, beziehungsweise unter „low-flow“ Sauerstofftherapie wurden exkludiert. Die Kohorte wurden in zwei Gruppen aufgeteilt. Die Behandlungsgruppe (n = 67) wurde mit der Standard-Therapie, sowie mit Ruxolitinib für mindestens drei Tage behandelt, die Kontrollgruppe (n = 70) erhielt lediglich die Standard-Therapie. Als primäre Outcomes wurden Mortalität und Überlebensraten erhoben. Die Ergebnisse wurden zwischen den Gruppen kontrastiert. Die sekundären Outcomes umfassen unter anderem die Länge des Intensiv-/Krankenhausaufenthaltes, den Einfluss der Ruxolitinib Behandlung auf die invasive Beatmung, sowie die Progression pro-inflammatorischer Marker während der Ruxolitinib Behandlung.
Die Krankenhausmortalitätsrate der Behandlungsgruppe betrug 47,76 % (32/67), wohingegen sich in der Kontrollgruppe eine Mortalität von 41,43 % (29/70) zeigte. In der Subgruppenanalyse von Patienten die Ruxolitinib, sowie eine Behandlung mit einer veno-venösen extrakorporalen Membranoxygenierung (vv ECMO) (n = 42) erhielten betrug
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die Mortalitätsrate 69,05%, ohne diese lag die Mortalitätsrate lediglich bei 12 %. Der Log-Rank-Test zeigte einen statistisch signifikanten Überlebensunterschied zwischen den beiden Gruppen (χ² = 12,7 p <0,001). Die mediane Überlebenszeit in der Behandlungsgruppe betrug 27 Tage, in der Kontrollgruppe hingegen nur 15 Tage. Das hazard ratio zu versterben war erhöht in invasiv beatmeten Patienten (hazard ratio 3,7; 95 % Konfidenzintervall 1,54-8,88, p=0,003). Keiner der nicht-invasiv beatmeten Patienten starb unter Ruxolitinib Therapie. Ruxolitinib konnte weder die mediane Dauer des Intensivaufenthaltes im Vergleich zur Standardtherapie verkürzen (Behandlungsgruppe 18 Tage (Interquartilsabstand 13), vs. Kontrollgruppe 8 (Interquartilsabstand 7,75); p<0,001), noch die mediane Dauer der Hospitalisierung. Die mediane Dauer der invasiven Beatmung war in der Behandlungsgruppe länger als in der Kontrollgruppe (Behandlungsgruppe 20,5 Tage (Interquartilsabstand 18) vs. Kontrollgruppe 6,5 Tage (Interquartilsabstand 8,25); p<0,001). Ein Abwärtstrend konnte für C-reaktives Protein und Interleukin-6 nachgewiesen werden. Anzeichen von Toxizität unter der Behandlung mit Ruxolitinib lagen nicht vor.
Die Ergebnisse demonstrieren das Ruxolitinib keine Reduktion der Mortalität in einer Patientenkohorte mit schwerer Organdysfunktion und unter zusätzlicher veno-venöser extrakorporaler Membranoxygenierung erzielte. Allerdings weisen sie auf die Notwendigkeit der weiteren Investigation des Medikamentes in schwer erkrankten Patienten ohne extrakorporale Membranoxygenierung hin. Die Ergebnisse untermauern bestehende Forschungsergebnisse bezüglich der Auswirkung der Beatmung auf die Mortalität. Die Überlebensrate von Patienten, die Ruxolitinib und eine nicht-invasive Beatmung erhielten, stimmt mit früheren Untersuchungen überein und unterstreicht das Konzept eines begrenzten Zeitrahmens für die Verabreichung von Ruxolitinib. Vorausgegangene Untersuchungen hatten auf eine Reduktion der Sterblichkeit bei invasiv beatmeten Patienten unter Ruxolitinib Therapie hingewiesen; dies konnte in der vorliegenden Studie nicht bestätigt werden. Die oben beschriebene Reduktion der pro-inflammatorischen Marker ist jedoch im Einklang mit vorhandener Literatur. Trotz des retrospektiven Studiendesigns, analysiert die Studie eine vergleichsweise große Behandlungsgruppe, sowie Subgruppen. Die Analyse der vorliegenden Daten suggeriert, dass Ruxolitinib in dem beschriebenen Setting kritisch diskutiert werden muss. Dennoch ist eine endgültige Empfehlung erst nach weiterer, bestenfalls prospektiver Investigation möglich
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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