13 research outputs found
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
- Author
- A.
- Abdelmohsen K.
- Abe A.
- Abedin M. J.
- Abeliovich H.
- Adachi H.
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- Al Rubeai M.
- Albaiceta G. M.
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- Publication venue
- Publication date
- 22/09/2015
- Field of study
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field
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- Abbass Hakam
- Adhikari Neill
- Affleck Julia
- Agno Sathianathan Ronan
- Ahmad Norfaizan
- Ahmed Iram
- Ainscough Kate
- Al Qasim Eman
- Al Swaidan Lolowa
- Al-Bassam Wisam
- Al-Beidh Farah
- Al-Beidh Farah
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- Angus Derek C
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- van Bentum Puijk Wilma
- van Bentum-Puijk Wilma
- van Bentum-Puijk Wilma
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- van de Veerdonk Frank
- van de Veerdonk Frank
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- van der Poll Tom
- van’t Hoff Willian
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- Vautier Sarah
- Vazquez-Grande Gloria
- Venkatesh Bala
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- Walsh Tim
- Walsham James
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- Watkins Claire
- Watpool Irene
- Watters Malcolm
- Waugh Victoria
- Webb Steve
- Webb Steven A
- Wedd Steve
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- Weissman Alexandra
- Wells Colin
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- Wetherill Bill
- Whelan Ruth
- Whileman Amanda
- Whitbread Jennifer
- White Hayden
- White Ian
- White Katie
- Whitehead Christina
- Wibrow Bradley
- Wigbers J
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- Williams Erin
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- Williamson James
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- Wilson Maggie
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- Wood Erica
- Wood Hannah
- Wood Tracy
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- Woods Lindsey
- Worner Ruth
- Wren Jess
- Wren Lynn
- Wrey Brown Caroline
- Writing Committee for the REMAP-CAP Investigators
- Xavier Kugan
- Xia Le Tai Charlotte
- Yarad Elizabeth
- Yates David
- Young Chelsea
- Young Ian
- Young Meredith
- Young Paul
- Yusuff Hakeem
- Zaharia Miahela Florentina
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zammit Claire
- Zapalac Marija
- Zarychanski Ryan
- Zarychanski Ryan
- Zhao Xiao Bei
- Zinzoni Vanessa
- Zitter Letizia
- Đimoti Renata
- Publication venue
- JAMA: Journal of the American Medical Association
- Publication date
- 06/10/2020
- Field of study
Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707
Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19
- Author
- ?ivko Iris
- Abbass Hakam
- Abdeladim Lilia
- Abdelhady Hesham
- Abdelkharim Hussam
- Abdelrazik Marwa
- Abdi Zakee
- Abdukahil Sheryl Ann
- Abel Lynn
- Abraham Jacinta
- Abrahamson Gail
- Abusamra Yousuf
- Aceto Romina
- Adams Nick
- Adams Peter
- Adebambo Olumide
- Adhikari Neill
- Adhikari Sheetal
- Affleck Julia
- Agha Gloria
- Aghemo Alessio
- Agno Ronan
- Ahmad Norfaizan
- Ain Quratul
- Ainscough Kate
- Ainsworth James
- Aitken Lindianne
- Akamp Ceren
- Al Enezi Farhan
- Al-Bassam Wisam
- Al-Beidh Farah
- Albert Martin
- Albrett Jonathan
- Alderman Meera
- Aldo Bonizzoni Matteo
- Alegria Ana
- Alessandro Carà Gianmarco
- Alexander Brian
- Alexander Peter
- Alfonso Jordan
- Ali Maryam
- Ali Murtaza
- Allam Hayat
- Allen Barbara
- Allen Louise
- Allibone Suzanne
- Almeshhedani Hasham
- AlQahtani Samah
- Alswaidan Lolowa
- Altomy Mohammed
- Al Amri Ali
- Al Qasim Eman
- Amatya Sameena
- Ambrosino Richard
- Anderson Thomas
- Andreae Mark
- Aneman Anders
- Angus Derek C.
- Anjum Aisha
- Ankert Juliane
- Annane Djillali
- Anne-Laure Fedou
- Anstey Matthew
- Antcliffe David
- Anthony Alpha
- Antoine Marchalot
- Antoine Pierre
- Antoine Studer
- Anumakonda Vikram
- Aparicio Christelle
- Aquino Maia
- Arabi Yaseen M.
- Arachchige Malka
- Aravindan Latha
- Arbane Gill
- Archambault Patrick
- Archer Simon
- Aref Noah
- Arias Ana-Marie
- Arias Sonia
- Arishi Hatim
- Arnold Donald
- Arnold John
- Arnott Andrew
- Arora Anand
- Aryal Diptesh
- Asghar Adeeba
- Asif Namra
- Aspinwall Angelique
- Attokaran Antony
- Attwood Ben
- Au Carly
- Audry Mathilde
- Austin Karen
- Austin Pauline
- Auvet Adrien
- Avard Bronwyn
- Awan Sidra
- Ayee Robert
- Azaiz Amine
- Azzaui Harun
- Babu Suresh
- Bacon Gina
- Badalamenti Salvatore
- Badie Julio
- Bagavathy Kavitha
- Bagot Catherine
- Bagshaw Sean
- Baig Nadia
- Baikady Ravishankar
- Bailey Lucy
- Baillie Kenneth
- Bain William
- Baker Alice
- Baker Evelyn
- Baker Stuart
- Bakthavatsalam Dhanalakshmi
- Balaie Morteza
- Balls-Burgess Sam
- Bamford Amy
- Bamford Peter
- Banach Dorota
- Bannard-Smith Jonathan
- Barbash Ian
- Barber Russell
- Barbier François
- Barge Deborah
- Bariola Ryan
- Barker Gareth
- Barker Stephanie
- Barnes Nicky
- Baron Rebecca M.
- Barreau Amelie
- Barreau Amélie
- Bart Robert
- Bartholomew Jazz
- Bartley Shauna
- Barton David
- Barton Frances
- Bashyal Archana
- Basile Kim
- Bass Frances
- Bassford Christopher
- Bastos Joana Margarida Pereira Sousa
- Bates Michelle
- Bates Samantha
- Batista Teresa Margarida Oliveira
- Bauchmuller Kris
- Bayne Madeleine
- Bean Sarah
- Beane Abi
- Beane Abigail
- Beard Gregory
- Beasley Richard
- Beaudoin Rosalie
- Beavis Sarah
- Beddows Seonaid
- Bedford Caroline
- Beer Deborah
- Beer Sally
- Begin Phillipe
- Begum Salma
- Bell Gillian
- Bellemare David
- Belletti Allesandro
- Bendjemar Lynda
- Benettaib Fatna
- Bensen Nicole
- Bentley Andrew
- Benyon Sarah
- Benzekri Dalila
- Beqai Besa
- Berdaguer Fernando
- Beresford Stephanie
- Bergin Colin
- Berry Lindsay R.
- Berry Scott
- Berryman Emily
- Bertel Melanie
- Best-Lane Janis
- Besten Henny
- Bevan Emily
- Bewley Jeremy
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- Bonten Marc J. M.
- Borgatta Barbara
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- De Bus Liesbet
- de Courcy-Golder Kim
- de Groot Klaas
- de Jong Menno
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- Depuydt Pieter
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- Derde Lennie P. G.
- Deshpande Kush
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- Deye Nicolas
- de la Fuente Carmen
- De Waele Jan
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- Estcourt Lise J.
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- Goebeler M.E.
- Golden David
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- Gordon Anthony C.
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- Haldeos Anne
- Hall Alistair S
- Hall Amelia
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- Higgins Alisa M.
- Hill Claire
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- Hornsby James
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- Horvat Christopher M.
- Howcroft Clare
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- Huang David T.
- Hughes Debbie
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- Kim Edy Y.
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- Kremling Julius
- Kreß Gabriele
- Krishnamoorthy S
- Krishnamurthy Vinodh
- Kruger Peter
- Kruisdijk-Gerritsen Arriette
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- Lawler Patrick R.
- Le Basnier Elliot
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- Liu Theresa
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- Marshall Lucy
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- McAdams David
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- McCarthy Aine
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- McKee Madeleine
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- McVerry Bryan J.
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- Woodward Robert
- Woolett Melissa
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- Wright Kim
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- Yamagishi Yoshiaki
- Yamashita Chizuru
- Yang Yang
- Yarad Elizabeth
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- Yates David
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- Youngstein Taryn
- Yu Haili
- Yusuff Hakeem
- Zaharia Mihaela
- Zaidi Abbas
- Zaki Ahmed
- Zaman Mohsin
- Zarychanski Ryan
- Zdanavidiene Ausra
- Zhao Xiao
- Zinzoni Vanessa
- Zitter Letizia
- Zouita Louisa
- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 11/04/2023
- Field of study
IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19.
Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19.
DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022).
INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days.
MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes.
RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively).
CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes.
TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
Recommended from our members
Restrictive or Liberal Transfusion Strategy in Myocardial Infarction and Anemia
- Author
- Abbott J. Dawn
- Alexander John H.
- Alsweiler Caroline
- Bertolet Marnie
- Bouleti Claire
- Brooks Maria Mori
- Carrier Francois Martin
- Carson Jeffrey L.
- Chaitman Bernard R.
- Chatzizisis Ioannis
- Cooper Howard A.
- Daneault Benoit
- de Barros E Silva Pedro Gabriel Melo
- DeFilippis Andrew P.
- Ducrocq Gregory
- Fergusson Dean A.
- Ferrari Emile
- Fordyce Christopher B.
- Ghafghazi Shahab
- Glynn Simone A.
- Goldsweig Andrew M.
- Goodman Shaun G.
- Hébert Paul C.
- Investigators MINT
- Kelsey Sheryl F.
- Kim Sarang
- Kostis William J.
- Lattuca Benoit
- Lopes Renato D.
- Menegus Mark A.
- Neary John D.
- Noveck Helaine
- Polonsky Tamar S.
- Potter Brian J.
- Puymirat Etienne
- Rao Sunil V.
- Senaratne Manohara
- Silvain Johanne
- Simon Tabassome
- Steg P. Gabriel
- Strom Jordan B.
- Tessalee Meechai
- Triulzi Darrell J.
- Uhl Lynn
- White Harvey D.
- Wood Frances O.
- Publication venue
- Publication date
- 01/01/2023
- Field of study
BACKGROUND: A strategy of administering a transfusion only when the hemoglobin level falls below 7 or 8 g per deciliter has been widely adopted. However, patients with acute myocardial infarction may benefit from a higher hemoglobin level. METHODS: In this phase 3, interventional trial, we randomly assigned patients with myocardial infarction and a hemoglobin level of less than 10 g per deciliter to a restrictive transfusion strategy (hemoglobin cutoff for transfusion, 7 or 8 g per deciliter) or a liberal transfusion strategy (hemoglobin cutoff, <10 g per deciliter). The primary outcome was a composite of myocardial infarction or death at 30 days. RESULTS: A total of 3504 patients were included in the primary analysis. The mean (±SD) number of red-cell units that were transfused was 0.7±1.6 in the restrictive-strategy group and 2.5±2.3 in the liberal-strategy group. The mean hemoglobin level was 1.3 to 1.6 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group on days 1 to 3 after randomization. A primary-outcome event occurred in 295 of 1749 patients (16.9%) in the restrictive-strategy group and in 255 of 1755 patients (14.5%) in the liberal-strategy group (risk ratio modeled with multiple imputation for incomplete follow-up, 1.15; 95% confidence interval [CI], 0.99 to 1.34; P = 0.07). Death occurred in 9.9% of the patients with the restrictive strategy and in 8.3% of the patients with the liberal strategy (risk ratio, 1.19; 95% CI, 0.96 to 1.47); myocardial infarction occurred in 8.5% and 7.2% of the patients, respectively (risk ratio, 1.19; 95% CI, 0.94 to 1.49). CONCLUSIONS: In patients with acute myocardial infarction and anemia, a liberal transfusion strategy did not significantly reduce the risk of recurrent myocardial infarction or death at 30 days. However, potential harms of a restrictive transfusion strategy cannot be excluded. (Funded by the National Heart, Lung, and Blood Institute and others; MINT ClinicalTrials.gov number, NCT02981407.)
Using research to prepare for outbreaks of severe acute respiratory infection
- Author
- . ()
- . ()
- Al Qasim E. (Eman)
- Ala-kokko T. (Tero)
- Angus D. C. (Derek C.)
- Antoine M. (Marchalot)
- Arabi Y. M. (Yaseen M.)
- Awasthi S. (Shally)
- Bahinskaya I. (Ilona)
- Baillie J. K. (John Kenneth)
- Bentley A. (Andrew)
- Bory S. (Sotharith)
- Browne T. (Troy)
- Browne T. S. (T. S.)
- Bruel C. (Cedric)
- Bruyere R. (Raomi)
- Campbell L. (Lewis)
- Carrier F. M. (Francois Martin)
- Carson G. (Gail)
- Chan W. M. (Wai Ming)
- Chang Y. (Youjin)
- Charles A. G. (Anthony G.)
- Cheng A. C. (Allen C.)
- Chiche J.-D. (Jean-Daniel)
- Cho J. H. (Jae Hwa)
- Choi W.-I. (Won-Il)
- Christian M. D. (Michael D.)
- Cobb J. P. (J. Perren)
- Daix T. (Thomas)
- Djillali A. E. (Annane E.)
- Dunning J. (Jake)
- Egi M. (Moritoki)
- EllazarHumber E. (Edward)
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- Everett D. (Dean)
- Fabienne T. (Taimon)
- Farshait N. (Nataly)
- Florence K.-P. (Komurian-Pradel)
- Forceville X. (Xavier)
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- Kazemi A. (Alex)
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- Kuitunen A. (Anne)
- Lamontagne F. (Francois)
- Lee H. B. (Heung Bum)
- Lee W.-Y. (Won-Yeon)
- Li I. W. (Iris Wai Sum)
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- Powis J. (Jeff)
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- Pulkkinen A. (Anni)
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- Raberahona M. (Mihaja)
- Ramirez-Venegas A. (Alejandra)
- Razanazatovo N. (Norosoa)
- Rello J. (Jordi)
- Rishu A. (Asgar)
- Riviello E. D. (Elisabeth D.)
- Rowan K. (Kathy)
- Ruberto A. J. (Aaron J.)
- Santamaria J. (John)
- Semple C. (Calum)
- Shindo N. (Nahoko)
- Siami S. (Shidasp)
- Sim Y. S. (Yun Su)
- Sin W. C. (Wai Ching)
- Som L. (Leakhann)
- Sonawane R. (Ravikiran)
- Sylvain H. (Habarurema)
- Teav B. (Bunlor)
- Tiercelet K. (Kelly)
- Twagirumugabe T. (Theogene)
- Ubiergo S. U. (Sebastian Ugarte)
- Umuhire O. F. (Olivier Felix)
- Uyeki T. M. (Timothy M.)
- Valkonen M. (Miia)
- van Doom H. R. (H. Rogier)
- Vann M. (Mich)
- Wallace D. J. (David J.)
- Webb S. A. (Steve A. R.)
- Welters I. (Ingeborg)
- West T. E. (T. Eoin)
- Young P. (Paul)
- Publication venue
- 'BMJ'
- Publication date
- 01/01/2019
- Field of study
Abstract
Severe acute respiratory infections (SARI) remain one of the leading causes of mortality around the world in all age groups. There is large global variation in epidemiology, clinical management and outcomes, including mortality. We performed a short period observational data collection in critical care units distributed globally during regional peak SARI seasons from 1 January 2016 until 31 August 2017, using standardised data collection tools. Data were collected for 1 week on all admitted patients who met the inclusion criteria for SARI, with follow-up to hospital discharge. Proportions of patients across regions were compared for microbiology, management strategies and outcomes. Regions were divided geographically and economically according to World Bank definitions. Data were collected for 682 patients from 95 hospitals and 23 countries. The overall mortality was 9.5%. Of the patients, 21.7% were children, with case fatality proportions of 1% for those less than 5 years. The highest mortality was in those above 60 years, at 18.6%. Case fatality varied by region: East Asia and Pacific 10.2% (21 of 206), Sub-Saharan Africa 4.3% (8 of 188), South Asia 0% (0 of 35), North America 13.6% (25 of 184), and Europe and Central Asia 14.3% (9 of 63). Mortality in low-income and low-middle-income countries combined was 4% as compared with 14% in high-income countries. Organ dysfunction scores calculated on presentation in 560 patients where full data were available revealed Sequential Organ Failure Assessment (SOFA) scores on presentation were significantly associated with mortality and hospital length of stay. Patients in East Asia and Pacific (48%) and North America (24%) had the highest SOFA scores of >12. Multivariable analysis demonstrated that initial SOFA score and age were independent predictors of hospital survival. There was variability across regions and income groupings for the critical care management and outcomes of SARI. Intensive care unit-specific factors, geography and management features were less reliable than baseline severity for predicting ultimate outcome. These findings may help in planning future outbreak severity assessments, but more globally representative data are required
Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356
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- Publication venue
- 'Informa UK Limited'
- Publication date
- 01/01/2016
- Field of study
No abstract available
Long-term (180-Day) outcomes in critically Ill patients with COVID-19 in the REMAP-CAP randomized clinical trial
- Author
- Abbass H
- Abdeladim L
- Abdelhady H
- Abdelkharim H
- Abdelrazik M
- Abdi Z
- Abdukahil SA
- Abel L
- Abraham J
- Abrahamson G
- Abusamra Y
- Aceto R
- Adams P
- Adebambo O
- Adhikari N
- Affleck J
- Agha G
- Aghemo A
- Agno R
- Aguilar-Dano A
- Ahmad N
- Ain Q
- Ainscough K
- Ainsworth J
- Aitken L
- Akamp C
- Al Enezi F
- Al-Bassam W
- Al-Beidh F
- Albert M
- Albrett J
- Alderink B
- Alderman M
- Alegria A
- Alexander B
- Alexander P
- Alfonso J
- Ali F
- Ali M
- Ali M
- Allam H
- Allen B
- Allen L
- Allibone S
- AlQahtani S
- Alswaidan L
- Altaf W
- Altomy M
- Al Amri A
- Al Qasim E
- Amatya S
- Ambrosino R
- Anders J
- Anderson T
- Andreae M
- Andric Z
- Aneman A
- Angus DC
- Anjum A
- Ankert J
- Annane D
- Anne-Laure F
- Anstey M
- Antcliffe D
- Anthony A
- Antoine M
- Antoine P
- Anumakonda V
- Aparicio C
- Arabi YM
- Arachchige M
- Aravindan L
- Arbane G
- Archer S
- Aref N
- Arias A-M
- Arias S
- Arishi H
- Arnold D
- Arnold J
- Aryal D
- Asghar A
- Asif N
- Aspinwall A
- Attanayaka U
- Attokaran A
- Attwood B
- Au C
- Austin K
- Austin P
- Avard B
- Awan S
- Azaiz A
- Azergui N
- Azzaui H
- Babel J
- Babu S
- Bacon G
- Badalamenti S
- Badie J
- Bagavathy K
- Bagot C
- Bagshaw S
- Baig N
- Baikady R
- Baillie K
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- Baker S
- Bakthavatsalam D
- Balaie M
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- Publication venue
- 'American Medical Association (AMA)'
- Publication date
- 30/11/2022
- Field of study
Importance The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months
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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
- Author
- Abdelmohsen Kotb
- Abe Akihisa
- Abedin Md Joynal
- Abeliovich Hagai
- Adachi Hiroaki
- Adams Christopher M.
- Adams Peter D.
- Adeli Khosrow
- Adhihetty Peter J.
- Adler Sharon G.
- Agam Galila
- Agarwal Rajesh
- Aghi Manish K.
- Agnello Maria
- Agostinis Patrizia
- Aguilar Patricia V.
- Aguirre-Ghiso Julio
- Airoldi Edoardo M.
- Ait-Si-Ali Slimane
- Akematsu Takahiko
- Akporiaye Emmanuel T.
- Al-Rubeai Mohamed
- Albaiceta Guillermo M.
- Albanese Chris
- Albani Diego
- Albert Matthew L.
- Aldudo Jesus
- Alguel Hana
- Alirezaei Mehrdad
- Alloza Iraide
- Almasan Alexandru
- Almonte-Beceril Maylin
- Alnemri Emad S.
- Alonso Covadonga
- Altan-Bonnet Nihal
- Altieri Dario C.
- Alvarez Silvia
- Alvarez-Erviti Lydia
- Alves Sandro
- Amadoro Giuseppina
- Amano Atsuo
- Amantini Consuelo
- Ambrosio Santiago
- Amelio Ivano
- Amer Amal O.
- Amessou Mohamed
- Amon Angelika
- An Zhenyi
- Ana Gonzalez-Polo Rosa
- Anania Frank A.
- Andersen Stig U.
- Andley Usha P.
- Andreadi Catherine K.
- Andrieu-Abadie Nathalie
- Anel Alberto
- Ann David K.
- Anoopkumar-Dukie Shailendra
- Antonioli Manuela
- Aoki Hiroshi
- Apostolova Nadezda
- Aquila Saveria
- Aquilano Katia
- Araki Koichi
- Arama Eli
- Aranda Agustin
- Araya Jun
- Arcaro Alexandre
- Arias Esperanza
- Arimoto Hirokazu
- Ariosa Aileen R.
- Armstrong Jane L.
- Arnould Thierry
- Arozena Abraham Acevedo
- Arsov Ivica
- Asanuma Katsuhiko
- Askanas Valerie
- Asselin Eric
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- Atkin Julie D.
- Attardi Laura D.
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- Choubey Divaker
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- Chow Kuan-Chih
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- Chu Charleen T.
- Chuang Tsung-Hsien
- Chun Taehoon
- Chung Hyewon
- Chung Taijoon
- Chung Yuen-Li
- Chwae Yong-Joon
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- Ciarcia Roberto
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- Xu Ziheng
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- Yamanaka Koji
- Yamashina Shunhei
- Yamashiro Shigeko
- Yan Bing
- Yan Bo
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- Yan Zhen
- Yanagi Yasuo
- Yang Dun-Sheng
- Yang Jin-Ming
- Yang Liu
- Yang Minghua
- Yang Pei-Ming
- Yang Peixin
- Yang Qian
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- Yang Yi
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- Yang Zhihong
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- Yao Xiaofeng
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- Yasui Linda S.
- Ye Mingxiang
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- Yeganeh Behzad
- Yeh Elizabeth S.
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- Yi Fan
- Yi Long
- Yin Xiao-Ming
- Yip Calvin K.
- Yoo Yeong-Min
- Yoo Young Hyun
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- Yoshida Ken-Ichi
- Yoshimori Tamotsu
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- Yu Huixin
- Yu Jane J.
- Yu Jin-Tai
- Yu Jun
- Yu Li
- Yu W. Haung
- Yu Xiao-Fang
- Yu Zhengping
- Yuan Junying
- Yuan Zhi-Min
- Yue Beatrice Y. J. T.
- Yue Jianbo
- Yue Zhenyu
- Zacks David N.
- Zacksenhaus Eldad
- Zaffaroni Nadia
- Zaglia Tania
- Zakeri Zahra
- Zecchini Vincent
- Zeng Jinsheng
- Zeng Min
- Zeng Qi
- Zervos Antonis S.
- Zhang Donna D.
- Zhang Fan
- Zhang Guo
- Zhang Guo-Chang
- Zhang Hao
- Zhang Hong
- Zhang Hong
- Zhang Hongbing
- Zhang Jian
- Zhang Jian
- Zhang Jiangwei
- Zhang Jianhua
- Zhang Jing-pu
- Zhang Li
- Zhang Lin
- Zhang Lin
- Zhang Long
- Zhang Ming-Yong
- Zhang Xiangnan
- Zhang Xu Dong
- Zhang Yan
- Zhang Yang
- Zhang Yanjin
- Zhang Yingmei
- Zhang Yunjiao
- Zhao Mei
- Zhao Wei-Li
- Zhao Xiaonan
- Zhao Yan G.
- Zhao Ying
- Zhao Yongchao
- Zhao Yu-Xia
- Zhao Zhendong
- Zhao Zhizhuang J.
- Zheng Dexian
- Zheng Xi-Long
- Zheng Xiaoxiang
- Zhivotovsky Boris
- Zhong Qing
- Zhou Guang-Zhou
- Zhou Guofei
- Zhou Huiping
- Zhou Shu-Feng
- Zhou Xu-Jie
- Zhu Hongxin
- Zhu Hua
- Zhu Wei-Guo
- Zhu Wenhua
- Zhu Xiao-Feng
- Zhu Yuhua
- Zhuang Shi-Mei
- Zhuang Xiaohong
- Ziparo Elio
- Zois Christos E.
- Zoladek Teresa
- Zong Wei-Xing
- Zorzano Antonio
- Zughaier Susu M.
- Publication venue
- Publication date
- 01/01/2016
- Field of study
A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial
- Author
- Abrams Judith
- Adda Mireille
- Adderley Jane
- Adhikari Neill K. J.
- Adhikari Neill K. J.
- Aissaoui Nadia
- Alam Ahsan
- Albrett Jonathan
- Albright Robert C.
- Alcuaz Victoria
- Allam Hayat
- Altarelli Marco
- Amaral Andre
- Amsbaugh Amy
- Anderson Felicity
- Andreu Pascal
- Antunes Veronica
- Arbane Gill
- Argaud Laurent
- Arias Castro
- Asehnoune Karim
- Attwood Ben
- Auld Fiona
- Ayas Najib
- Aycinena Juan Carlos
- Azais Marie-Ange
- Bachler Mirjam
- Backhouse Felicity
- Bagshaw Sean M.
- Bagshaw Sean M.
- Bagshaw Sean M.
- Bagshaw Sean M.
- Baharlo Behrad
- Bai Guoqiang
- Bai Jing
- Baig Nadia
- Baig Nadia
- Bailey Matthew
- Baker Nerilee
- Ball Ian M.
- Ball Jonathan
- Barbar Saber Davide
- Barbier François
- Barchard Jennifer
- Bass Frances
- Bates Samantha
- Baudry Thomas
- Beck James
- Beehre Nina
- Bellemare David
- Belley-Cote Emilie
- Bellmann Romuald
- Bellomo Rinaldo
- Bellomo Rinaldo
- Benettaib Fatna
- Benoit Luc
- Benton Jane
- Benzekri Dalila
- Bergin Colin
- Bihari Shailesh
- Bihorac Azra
- Bird Sarah
- Bitker Laurent
- Board Jasmin
- Bociek Aneta
- Bohé Julien
- Boisrame-Helms Julie
- Boivin Annick
- Bojic Andja
- Bone Allison
- Boschert Catherine
- Bouisse Camille
- Boulain Thierry
- Boulet Éric
- Boumahni Dounia
- Bourchard Pierre-Alexandre
- Bowman Katie
- Bracke Stephanie
- Bradford Celia
- Brailsford Jane
- Brandtner Anna
- Bretagnol Anne
- Brickell Kathy
- Broadfield Emma
- Brodutch Shira
- Brooks Jenny
- Brown Gillian
- Brown Sherry
- Browne Troy
- Buehner Ulrike
- Buhr Heidi
- Burke Tara
- Burns Karen
- Buscher Hergen
- Butler Magdalena
- Butler Susie
- Cahill Hazel
- Cailhier Jean-François
- Callahan Jean Christophe
- Callender Owen
- Campbell Eileen
- Campbell Troy
- Campbell Victoria
- Campisi Josie
- Camporota Luigi
- Campos Sara
- Canet Emmanuel
- Cantien Marie
- Carbonnaeu Élaine
- Carles Michel
- Carney Dominic
- Carney Gayle
- Carpentier Dorothée
- Carrera Ron
- Carrier François-Martin
- Carson Joshua
- Carter Joseph
- Carungcong Jaime
- Carvelli Paula
- Cegarra Santiago
- Cennamo Armando
- Chadbourn Indra
- Chadwick Lesley
- Chan Peter
- Chee Nigel
- Chen Man
- Chen Yan
- Chen Zhenzhen
- Chenaf Samir
- Cheung Winston
- Chevrel Guillaume
- Chiella Bianca
- Chimunda Tim
- Chudeau Nicolas
- Cinotti Raphaël
- Cirone Robert
- Clarey Emma
- Clark Amy
- Clark Edward
- Clark Michele
- Clarke France
- Cleophax Cedric
- Clere-Jehl Raphael
- Cloutier Eve
- Cohen Yves
- Cole Jade
- Cole Louise
- Coles Jennifer
- Colin Gwenhaël
- Collins Amy
- Combes Alain
- Commeureuc Morgane
- Condin Christopher
- Conner Louise
- Cooper Lauren
- Corcoran Eleanor
- Costa Patricia
- Costerousse Olivier
- Coupez Elisabeth
- Cour Martin
- Cowdrey Keri-Anne
- Creary Thais
- Crosby Laura
- Cross Rosalba
- Cunningham Mishell
- Cupka Julie
- da Costa Bruno R.
- Daniels Alison
- Dargent Auguste
- Davies Tracy Michelle
- De Crop Luc
- De La Salle Sylvie
- De Prost Nicolas
- De Watteville Aude
- Decalvele Maxens
- Dechanet Aline
- Dekeyser Thibault
- Delabranche Xavier
- Delaney Anthony
- Delecolle Lucie
- Delgado Carlos Castro
- Delisle-Thibault Charles
- Demeure Dominique
- Demiri Suela
- Demoule Alexandre
- Deng Fuxing
- Derrien Benoit
- Despy Liesl
- Dessap Armand Mekontso
- Devereaux Kelson
- Di Nella Michelle
- Diehl Jean-Luc
- Diel Naomi
- Dignam Gemma
- Dilawershah Maria
- Ding Lili
- Ding Ruiqi
- Ditlbacher Adelheid
- Dodek Peter
- Dominy Clive
- Dong Lei
- Dong Xin
- Dooley Natalie
- Doran Peter
- Dorfman Robert
- Dos Santos Sandra
- Dres Martin
- Dreyfuss Didier
- Dreyfuss Didier
- Drover John
- Du Bin
- Du Bin
- Duan Meili
- Duffy Jane
- Duffy Karina
- Dufour Nicolas
- Duggan Shelley
- Duke Graeme
- Dun Shijuan
- Dyett John
- D’Aragon Frédérick
- Eastwood Glenn M.
- Eckert Philippe
- Efron Philip
- Elderkin Tania
- Elias Madona
- Elizabeth Wilcox M.
- Eller Philipp
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- Gallagher Martin P.
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- Gibson Neil
- Giebel Shelley
- Gilder Eileen
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- Gomes Brigette
- Gomez Raquel
- Goodson Jennifer
- Gordon Boyd J.
- Goulart Joyce McKenney
- Goulart Joyce McKenney
- Goundry Stephanie
- Grainger Lia
- Grangé Steven
- Grant Alice
- Grant Caroline
- Gray Geraldine
- Grenier Stéphanie
- Gresham Rebecca
- Grillot Nicolas
- Guerot Emmanuel
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- Guitton Christophe
- Guo Dongchen
- Guo Litao
- Gurung Babita
- Gutierrez David
- Guy Zoe
- Haljan Gregory
- Hall Adam
- Hallion Jane
- Haltia Paivi
- Hambrook Geraldine
- Hammond Naomi
- Hamshere Alexandra
- Hang Lele
- Harasemiw Oksana
- Harkett Samanth
- Harkins Margaret
- Harmon John
- Harris Claire-Louise
- Harrop Clare
- Hartig Frank
- Harvey Dan
- Hashemighouchani Haleh
- Haslam Nicole
- Hasslacher Julia
- Hauschild Caroline
- Hazelton Tracy
- He Xiandi
- He Xiaona
- Heidegger Claudia
- Heinonen Jonna
- Henderson Seton
- Henderson Steven
- Hendry Deborah
- Hernandez Clara
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- Herridge Margaret S.
- Higson Vicki
- Hill Dianne
- Hill Helen
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- Inkinen Outi
- Investigators STARRT-AKI
- Jackson Carolyn
- Jackson David
- Jagannathan Vijay
- Jalkanen Ville
- Jang Ryan
- Janin Pierre
- Ji Xiaojun
- Jim Kym
- Jin Xia
- Joannidis Michael
- Joannidis Michael
- Johnson Emily
- Johnston Andy
- Joseph Gipsy
- Judd Harriet
- Junge Andrea
- Järvisalo Mikko J.
- Kamel Toufik
- Kapoor Ritoo
- Karachi Tim
- Karlsson Sari
- Kashani Kianoush B.
- Kaufman Melissa
- Kaur Navjot
- Kavikondala Kanthi
- Kaye Callum
- Keet Owen
- Kentala Satu
- Kerr Deborah
- Khalid Imrana
- Ki Vincent
- Kiley Sean
- Kirkham Simon
- Kissling Sébastien
- Klein David
- Klein Sebastian
- Knight David
- Knott Cameron
- Koglberger Paul
- Kokotsis Nicos
- Kol Mark
- Koottayi Sathyajith
- Korhonen Anna-Maija
- Kruger Peter
- Kuitunen Anne
- Kummerlen Christine
- Kutsogiannis Demetrios J.
- Küllmar Mira
- Lacave Guillaume
- Lacherade Jean Claude
- Ladouceur Marilène
- Lafrance Jean-Philippe
- Lagarrigue Matthieu Henry-
- Lakatos Louis
- Lakhal Karim
- Lambert Bridget
- Lamontagne François
- Lamontagne François
- Lamontagne François
- Landais Mickael
- Landoni Giovanni
- Lapinsky Stephen
- Lappi Eliria
- Large Audrey
- Latimer-Bell Charlotte
- Latta Laura
- Laurie Gordon
- Lauzier François
- Lawrence Cassie
- Le Moal Charlène
- Leaver Susannah
- Lebert Christine
- LeBlanc Guillaume
- Lebrasseur Martine
- Lee Sandra
- Leivo Keijo
- Lellouche Francois
- Lembo Rosalba
- Lenga Ilan
- Lesona Eden
- Levoranta Markus
- Li Hao
- Li Jian
- Li Jianquan
- Li Jing
- Li Min
- Li Nan
- Li Rui
- Lian Yingtao
- Liangos Orfeas
- Licari Elisa
- Lim Rosario
- Lin Jin
- Lin Jincan
- Liu Airan
- Liu Cheng
- Liu Hongjuan
- Liu Jingfeng
- Liu Kathleen D.
- Liu Manli
- Liu Pei
- Liu Xingang
- Liu Yu
- Liu Zhongmin
- Liu Zhou
- Liu Zhuang
- Lizotte Patricia
- Lobaz Steve
- Lombardi Gaetano
- Long Dali
- Long Stephanie
- Lord Jenny
- Lowrey Julie
- Lu Kun
- Lu Liping
- Lyas Claretha
- Lynch Matthew
- Lynch Matthew
- Långsjö Jaakko
- Ma Hongye
- MacIntyre Erika
- Magder Sheldon
- Maguire Teena
- Maizel Julien
- Malila Kaisa
- Mallaird Samia Abed
- Mallet Maxime
- Manns Braden J.
- Manso Katarina
- Marceron Alina
- Marchalot Antoine
- Marchand Joannie
- Margalef Jordi
- Margarson Michael
- Marinoff Nicole
- Marios Clémence
- Marotti Martina
- Marque Sophie
- Martin Emma
- Martin-Lefevre Laurent
- Martino Frédéric
- Martins Laura
- Marzaroli Matteo
- Marzouk Mehdi
- Masi Paul
- Maslove David
- Mason Chris
- Mason Sophie
- Mason Tracy
- Masse Marie-Hélène
- Masters Kristy
- Matheson Elisha
- Mathonnet Armelle
- Mayaux Julien
- Mayette Michael
- Mazer David
- McArthur Colin
- McAuley Daniel F.
- McAuley Danny F.
- McCall Philip
- McClure Jason
- McConnochie Rachael
- McCoshen Lorena
- McCracken Phoebe
- McGain Forbes
- McGlone Philip
- McGloughlin Steve
- McGonigal Elizabeth
- McGuinness Shay
- McGuinness Shay
- McGuinness Shay P.
- McIntyre Lauralyn
- Mckay-Vucago Agnes
- McKerrow Elizabeth
- McLaughlan Derek
- Meehan Sharon
- Mehrtens Jan
- Mehta Navdeep
- Mehta Sangeeta
- Mei Huaxian
- Mei Jing
- Meng Zhaoli
- Merdji Hamid
- Meredith Megan
- Messika Jonathan
- Mew Louise
- Meyer Jason
- Meziani Ferhat
- Millen Tina
- Mitchell Wendy
- Mo Min
- Monnier Alexandra
- Monti Giacomo
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- Moon Angela
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- Morawiec Elise
- Moreland Gayle
- Morgan Matt
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- Yao Lan
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- Yehia Aihem
- Young Helen
- Young Meredith
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- Yu Zhui
- Zahirieh Alireza
- Zampieri Fernando G.
- Zangrillo Alberto
- Zarbock Alexander
- Zeng Qinjing
- Zhang Jichen
- Zhang Lei
- Zhang Meng
- Zhang Minwei
- Zhang Songsong
- Zhao Dan
- Zhao Mengya
- Zhao Shibing
- Zhao Shuangping
- Zhi Deyuan
- Zhou Qi
- Zhou Xiao
- Zhuang Haizhou
- Zotter Klemens
- Zuber Benjamin
- Publication venue
- 'Springer Science and Business Media LLC'
- Publication date
- 01/01/2022
- Field of study
Background
Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework.
Methods
We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression.
Results
The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66.
Conclusions
In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation