LIVIVO - Search results -

Search results

Result 1 - 10 of total 23

Search options

Article ; Online: A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2.

2024 Volume 177, Issue 3, Page(s) 343–352

Abstract: Background: The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high ... ...

Abstract	Background: The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib. Objective: To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile. Design: Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04401579). Setting: Sixty-seven trial sites in 8 countries. Participants: Adults hospitalized with COVID-19 ( Intervention: Baricitinib+remdesivir versus placebo+remdesivir. Measurements: Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories. Results: In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; Limitation: Secondary analysis of data collected before circulation of current SARS-CoV-2 variants. Conclusion: The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19. Primary funding source: National Institute of Allergy and Infectious Diseases.
MeSH term(s)	Adult ; Humans ; Antiviral Agents/adverse effects ; Azetidines ; COVID-19 ; COVID-19 Drug Treatment ; Immunologic Factors ; Purines ; Pyrazoles ; SARS-CoV-2 ; Sulfonamides ; Treatment Outcome ; Double-Blind Method
Chemical Substances	Antiviral Agents ; Azetidines ; baricitinib (ISP4442I3Y) ; Immunologic Factors ; Purines ; Pyrazoles ; Sulfonamides
Language	English
Publishing date	2024-02-27
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	336-0
ISSN	1539-3704 ; 0003-4819
ISSN (online)	1539-3704
ISSN	0003-4819
DOI	10.7326/M23-2593
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ua VI Zs.178/2: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Counting Monkeypox Lesions in Patient Photographs: Limits of Agreement of Manual Counts and Artificial Intelligence.

McNeil, Andrew J / House, David W / Mbala-Kingebeni, Placide / Mbaya, Olivier Tshiani / Dodd, Lori E / Cowen, Edward W / Nussenblatt, Véronique / Bonnett, Tyler / Chen, Ziche / Saknite, Inga / Dawant, Benoit M / Tkaczyk, Eric R

The Journal of investigative dermatology

2022 Volume 143, Issue 2, Page(s) 347–350.e4

MeSH term(s)	Humans ; Artificial Intelligence ; Mpox (monkeypox)
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2022.08.044
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui VI Zs.124: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Deconstructing the Treatment Effect of Remdesivir in the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1: Implications for Critical Care Resource Utilization.

Fintzi, Jonathan / Bonnett, Tyler / Sweeney, Daniel A / Huprikar, Nikhil A / Ganesan, Anuradha / Frank, Maria G / McLellan, Susan L F / Dodd, Lori E / Tebas, Pablo / Mehta, Aneesh K

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2021 Volume 74, Issue 12, Page(s) 2209–2217

Abstract: Background: The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how ... ...

Abstract	Background: The Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) found that remdesivir therapy hastened recovery in patients hospitalized with COVID-19, but the pathway for this improvement was not explored. We investigated how the dynamics of clinical progression changed along 4 pathways: recovery, improvement in respiratory therapy requirement, deterioration in respiratory therapy requirement, and death. Methods: We analyzed trajectories of daily ordinal severity scores reflecting oxygen requirements of 1051 patients hospitalized with COVID-19 who participated in ACTT-1. We developed competing risks models that estimate the effect of remdesivir therapy on cumulative incidence of clinical improvement and deterioration, and multistate models that utilize the entirety of each patient's clinical course to characterize the effect of remdesivir on progression along the 4 pathways above. Results: Based on a competing risks analysis, remdesivir reduced clinical deterioration (hazard ratio [HR], 0.73; 95% confidence interval [CI]: .59-.91) and increased clinical improvement (HR, 1.22; 95% CI: 1.08, 1.39) relative to baseline. Our multistate models indicate that remdesivir inhibits worsening to ordinal scores of greater clinical severity among patients on room air or low-flow oxygen (HR, 0.74; 95% CI: .57-.94) and among patients receiving mechanical ventilation or high-flow oxygen/noninvasive positive-pressure ventilation (HR, 0.73; 95% CI: .53-1.00) at baseline. We also find that remdesivir reduces expected intensive care respiratory therapy utilization among patients not mechanically ventilated at baseline. Conclusions: Remdesivir speeds time to recovery by preventing worsening to clinical states that would extend the course of hospitalization and increase intensive respiratory support, thereby reducing the overall demand for hospital care.
MeSH term(s)	Adenosine Monophosphate/analogs & derivatives ; Alanine/analogs & derivatives ; Antiviral Agents ; Critical Care ; Humans ; Oxygen ; SARS-CoV-2 ; COVID-19 Drug Treatment
Chemical Substances	Antiviral Agents ; remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX) ; Oxygen (S88TT14065)
Language	English
Publishing date	2021-08-18
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciab712
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1505: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 480: Show issues

Order via subito

Details ▾

Article ; Online: How do I… facilitate a rapid response to a public health emergency requiring plasma collection with a public-private partnership?

Miller, Maureen J / Skrzekut, Adam / Kracalik, Ian / Jones, Jefferson M / Lofy, Kathryn H / Konkle, Barbara A / Haley, N Rebecca / Duvenhage, Michael / Bonnett, Tyler / Holbrook, Michael / Higgs, Elizabeth / Basavaraju, Sridhar V / Paranjape, Suman

Transfusion

2021 Volume 61, Issue 10, Page(s) 2814–2824

Abstract: In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with ... ...

Abstract	In March 2020, there were no treatment options for COVID-19. Passive immune therapy including anti-SARS-CoV-2 hyperimmune globulin (hIVIG) was a logical candidate for COVID-19 therapeutic trials, given past success treating emerging pathogens with endogenous neutralizing antibodies. We established a plasma collection protocol for persons recovered from COVID-19. To speed recruitment in the first U.S. hotspot, Seattle, Washington, federal and state public health agencies collaborated with Bloodworks Northwest to collect convalescent plasma (CP) for manufacturing hIVIG. During March-December 2020, we identified and recruited prospective CP donors via letters to persons recovered from COVID-19 with laboratory-confirmed SARS-CoV-2 infection. Prospective donors were pre-screened and administered a medical history survey. Anti-SARS-CoV-2 neutralizing antibody (NAb) titers were classified as qualifying (≥1:80) or non-qualifying (<1:80) for enrollment based on a live virus neutralization assay. Generalized estimating equations were used to identify characteristics of donors associated with qualifying versus nonqualifying NAb titers. Overall, 21,359 letters resulted in 3207 inquiries, 2159 prescreenings with laboratory-confirmed SARS-CoV-2 infection, and 573 donors (27% of all pre-screenings with confirmed infection) who provided a screening plasma donation. Of 573 donors screened, 254 (44%) provided plasma with qualifying NAb titers, resulting in 1284 units for hIVIG manufacture. In a multivariable model, after adjusting for other factors, time (60 days) from COVID-19 symptom onset to screening was associated with lower odds of qualifying NAb (adjusted odds ratio = 0.67, 95% CI: 0.48-0.94). The collaboration facilitated a rapid response to develop and provide hIVIG for clinical trials and CP for transfusion. Only 1 in 12 donor inquiries resulted in a qualifying plasma donation. Challenges included recruitment and the relatively low percentage of persons with high NAb titers and limited screening capacity. This resource-intensive collaboration may not be scalable but informs preparedness and response strategies for plasma collection in future epidemics. Operational readiness plans with templates for screening, consent, and data collection forms are recommended.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Blood Specimen Collection ; COVID-19/therapy ; Emergencies ; Female ; Humans ; Immunization, Passive ; Male ; Middle Aged ; Public Health ; Public-Private Sector Partnerships ; SARS-CoV-2 ; Young Adult
Language	English
Publishing date	2021-09-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16630
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 284: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy.

Gauthreaux, Kathryn / Bonnett, Tyler A / Besser, Lilah M / Brenowitz, Willa D / Teylan, Merilee / Mock, Charles / Chen, Yen-Chi / Chan, Kwun C G / Keene, C Dirk / Zhou, Xiao-Hua / Kukull, Walter A

Journal of neuropathology and experimental neurology

2020 Volume 79, Issue 5, Page(s) 465–473

Abstract: It remains unclear what clinical features inform the accuracy of a clinical diagnosis of Alzheimer disease (AD). Data were obtained from the National Alzheimer's Coordinating Center to compare clinical and neuropathologic features among participants who ... ...

Abstract	It remains unclear what clinical features inform the accuracy of a clinical diagnosis of Alzheimer disease (AD). Data were obtained from the National Alzheimer's Coordinating Center to compare clinical and neuropathologic features among participants who did or did not have Alzheimer disease neuropathologic changes (ADNC) at autopsy. Participants (1854) had a clinical Alzheimer dementia diagnosis and ADNC at autopsy (Confirmed-AD), 204 participants had an AD diagnosis and no ADNC (AD-Mimics), and 253 participants had no AD diagnosis and ADNC (Unidentified-AD). Compared to Confirmed-AD participants, AD-Mimics had less severe cognitive impairment, while Unidentified-AD participants displayed more parkinsonian signs, depression, and behavioral problems. This study highlights the importance of developing a complete panel of biomarkers as a tool to inform clinical diagnoses, as clinical phenotypes that are typically associated with diseases other than AD may result in inaccurate diagnoses.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/pathology ; Autopsy ; Brain/pathology ; Female ; Humans ; Male ; Neuropathology
Language	English
Publishing date	2020-04-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3088-0
ISSN	1554-6578 ; 0022-3069
ISSN (online)	1554-6578
ISSN	0022-3069
DOI	10.1093/jnen/nlaa014
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Ui II Zs.134: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Ui II Zs.194: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Estimating associations between antidepressant use and incident mild cognitive impairment in older adults with depression.

Han, Fang / Bonnett, Tyler / Brenowitz, Willa D / Teylan, Merilee A / Besser, Lilah M / Chen, Yen-Chi / Chan, Gary / Cao, Ke-Gang / Gao, Ying / Zhou, Xiao-Hua

PloS one

2020 Volume 15, Issue 1, Page(s) e0227924

Abstract: Introduction: Previous studies have provided equivocal evidence of antidepressant use on subsequent cognitive impairment; this could be due to inconsistent modeling approaches. Our goals are methodological and clinical. We evaluate the impact of ... ...

Abstract	Introduction: Previous studies have provided equivocal evidence of antidepressant use on subsequent cognitive impairment; this could be due to inconsistent modeling approaches. Our goals are methodological and clinical. We evaluate the impact of statistical modeling approaches on the associations between antidepressant use and risk of Mild Cognitive Impairment (MCI) in older adults with depression. Methods: 716 participants were enrolled. Our primary analysis employed a time-dependent Cox proportional hazards model. We also implemented two fixed-covariate proportional hazards models-one based on having ever used antidepressants during follow-up, and the other restricted to baseline use only. Results: Treating antidepressant use as a time-varying covariate, we found no significant association with incident MCI (HR = 0.92, 95% CI: 0.70, 1.20). In contrast, when antidepressant use was treated as a fixed covariate, we observed a significant association between having ever used antidepressants and lower risk of MCI (HR = 0.40, 95% CI: 0.28, 0.56). However, in the baseline-use only model, the association was non-significant (HR = 0.84, 95% CI: 0.60, 1.17). Discussion: Our results were dependent upon statistical models and suggest that antidepressant use should be modeled as a time-varying covariate. Using a robust time-dependent analysis, antidepressant use was not significantly associated with incident MCI among cognitively normal persons with depression.
MeSH term(s)	Aged ; Aged, 80 and over ; Antidepressive Agents/adverse effects ; Cognition/drug effects ; Cognition/physiology ; Cognitive Dysfunction/complications ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/epidemiology ; Cognitive Dysfunction/physiopathology ; Cohort Studies ; Depression/complications ; Depression/drug therapy ; Depression/epidemiology ; Depression/physiopathology ; Female ; Follow-Up Studies ; Humans ; Male ; Models, Statistical ; Proportional Hazards Models ; Risk Factors
Chemical Substances	Antidepressive Agents
Language	English
Publishing date	2020-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0227924
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Endpoints for randomized controlled clinical trials for COVID-19 treatments.

Dodd, Lori E / Follmann, Dean / Wang, Jing / Koenig, Franz / Korn, Lisa L / Schoergenhofer, Christian / Proschan, Michael / Hunsberger, Sally / Bonnett, Tyler / Makowski, Mat / Belhadi, Drifa / Wang, Yeming / Cao, Bin / Mentre, France / Jaki, Thomas

Clinical trials (London, England)

2020 Volume 17, Issue 5, Page(s) 472–482

Abstract: Background: Endpoint choice for randomized controlled trials of treatments for novel coronavirus-induced disease (COVID-19) is complex. Trials must start rapidly to identify treatments that can be used as part of the outbreak response, in the midst of ... ...

Abstract	Background: Endpoint choice for randomized controlled trials of treatments for novel coronavirus-induced disease (COVID-19) is complex. Trials must start rapidly to identify treatments that can be used as part of the outbreak response, in the midst of considerable uncertainty and limited information. COVID-19 presentation is heterogeneous, ranging from mild disease that improves within days to critical disease that can last weeks to over a month and can end in death. While improvement in mortality would provide unquestionable evidence about the clinical significance of a treatment, sample sizes for a study evaluating mortality are large and may be impractical, particularly given a multitude of putative therapies to evaluate. Furthermore, patient states in between "cure" and "death" represent meaningful distinctions. Clinical severity scores have been proposed as an alternative. However, the appropriate summary measure for severity scores has been the subject of debate, particularly given the variable time course of COVID-19. Outcomes measured at fixed time points, such as a comparison of severity scores between treatment and control at day 14, may risk missing the time of clinical benefit. An endpoint such as time to improvement (or recovery) avoids the timing problem. However, some have argued that power losses will result from reducing the ordinal scale to a binary state of "recovered" versus "not recovered." Methods: We evaluate statistical power for possible trial endpoints for COVID-19 treatment trials using simulation models and data from two recent COVID-19 treatment trials. Results: Power for fixed time-point methods depends heavily on the time selected for evaluation. Time-to-event approaches have reasonable statistical power, even when compared with a fixed time-point method evaluated at the optimal time. Discussion: Time-to-event analysis methods have advantages in the COVID-19 setting, unless the optimal time for evaluating treatment effect is known in advance. Even when the optimal time is known, a time-to-event approach may increase power for interim analyses.
MeSH term(s)	Antiviral Agents/therapeutic use ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/drug therapy ; Coronavirus Infections/epidemiology ; Humans ; Pandemics ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/epidemiology ; Randomized Controlled Trials as Topic/methods ; SARS-CoV-2
Chemical Substances	Antiviral Agents
Keywords	covid19
Language	English
Publishing date	2020-07-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2138796-5
ISSN	1740-7753 ; 1740-7745
ISSN (online)	1740-7753
ISSN	1740-7745
DOI	10.1177/1740774520939938
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5831: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Unraveling the Treatment Effect of Baricitinib on Clinical Progression and Resource Utilization in Hospitalized COVID-19 Patients: Secondary Analysis of the Adaptive COVID-19 Treatment Randomized Trial-2.

Fintzi, Jonathan / Bonnett, Tyler / Tebas, Pablo / Marconi, Vincent C / Levine, Corri B / El Sahly, Hana M / McLellan, Susan L F / Benson, Constance A / Rostad, Christina A / Ganesan, Anuradha / Huprikar, Nikhil / Frank, Maria G / Mularski, Richard A / Atmar, Robert L / Park, Pauline K / Short, William R / Beigel, John H / Mehta, Aneesh K / Sweeney, Daniel A

Open forum infectious diseases

2022 Volume 9, Issue 7, Page(s) ofac219

Abstract: Background: The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT ...

Abstract	Background: The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT affected progression throughout hospitalization and utilization of intensive respiratory therapies. Methods: We characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment. We estimated the effect of BCT on cumulative incidence of clinical improvement and deterioration using competing risks models. We developed multistate models to estimate the effect of BCT on clinical improvement and deterioration and on utilization of respiratory therapies. Results: BCT resulted in more linear improvement and lower incidence of clinical deterioration compared with RMT (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95). The benefit was pronounced among participants enrolled on high-flow oxygen or noninvasive positive-pressure ventilation. In this group, BCT sped clinical improvement (HR, 1.21; 95% CI, 0.99 to 1.51) while slowing clinical deterioration (HR, 0.71; 95% CI, 0.48 to 1.02), which reduced the expected days in ordinal score (OS) 6 per 100 patients by 74 days (95% CI, -8 to 154 days) and the expected days in OS 7 per 100 patients by 161 days (95% CI, 46 to 291 days) compared with RMT. BCT did not benefit participants who were mechanically ventilated at enrollment. Conclusions: Compared with RMT, BCT reduces the clinical burden and utilization of intensive respiratory therapies for patients requiring low-flow oxygen or noninvasive positive-pressure ventilation compared with RMT and may thereby improve care for this patient population.
Language	English
Publishing date	2022-04-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofac219
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Effects of remdesivir in patients hospitalised with COVID-19: a systematic review and individual patient data meta-analysis of randomised controlled trials.

Amstutz, Alain / Speich, Benjamin / Mentré, France / Rueegg, Corina Silvia / Belhadi, Drifa / Assoumou, Lambert / Burdet, Charles / Murthy, Srinivas / Dodd, Lori Elizabeth / Wang, Yeming / Tikkinen, Kari A O / Ader, Florence / Hites, Maya / Bouscambert, Maude / Trabaud, Mary Anne / Fralick, Mike / Lee, Todd C / Pinto, Ruxandra / Barratt-Due, Andreas /

Lund-Johansen, Fridtjof / Müller, Fredrik / Nevalainen, Olli P O / Cao, Bin / Bonnett, Tyler / Griessbach, Alexandra / Taji Heravi, Ala / Schönenberger, Christof / Janiaud, Perrine / Werlen, Laura / Aghlmandi, Soheila / Schandelmaier, Stefan / Yazdanpanah, Yazdan / Costagliola, Dominique / Olsen, Inge Christoffer / Briel, Matthias

The Lancet. Respiratory medicine

2023 Volume 11, Issue 5, Page(s) 453–464

Abstract: Background: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in ...

Abstract	Background: Interpretation of the evidence from randomised controlled trials (RCTs) of remdesivir in patients treated in hospital for COVID-19 is conflicting. We aimed to assess the benefits and harms of remdesivir compared with placebo or usual care in these patients, and whether treatment effects differed between prespecified patient subgroups. Methods: For this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane COVID-19 trial registry, ClinicalTrials.gov, the International Clinical Trials Registry Platform, and preprint servers from Jan 1, 2020, until April 11, 2022, for RCTs of remdesivir in adult patients hospitalised with COVID-19, and contacted the authors of eligible trials to request individual patient data. The primary outcome was all-cause mortality at day 28 after randomisation. We used multivariable hierarchical regression-adjusting for respiratory support, age, and enrollment period-to investigate effect modifiers. This study was registered with PROSPERO, CRD42021257134. Findings: Our search identified 857 records, yielding nine RCTs eligible for inclusion. Of these nine eligible RCTs, individual data were provided for eight, covering 10 480 patients hospitalised with COVID-19 (99% of such patients included in such RCTs worldwide) recruited between Feb 6, 2020, and April 1, 2021. Within 28 days of randomisation, 662 (12·5%) of 5317 patients assigned to remdesivir and 706 (14·1%) of 5005 patients assigned to no remdesivir died (adjusted odds ratio [aOR] 0·88, 95% CI 0·78-1·00, p=0·045). We found evidence for a credible subgroup effect according to respiratory support at baseline (p Interpretation: This individual patient data meta-analysis showed that remdesivir reduced mortality in patients hospitalised with COVID-19 who required no or conventional oxygen support, but was underpowered to evaluate patients who were ventilated when receiving remdesivir. The effect size of remdesivir in patients with more respiratory support or acquired immunity and the cost-effectiveness of remdesivir remain to be further elucidated. Funding: EU-RESPONSE.
MeSH term(s)	Adult ; Humans ; COVID-19 ; COVID-19 Drug Treatment
Language	English
Publishing date	2023-02-21
Publishing country	England
Document type	Systematic Review ; Meta-Analysis ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(22)00528-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 7041: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Endpoints for randomized controlled clinical trials for COVID-19 treatments

Clin Trials

Abstract: BACKGROUND: Endpoint choice for randomized controlled trials of treatments for novel coronavirus-induced disease (COVID-19) is complex. Trials must start rapidly to identify treatments that can be used as part of the outbreak response, in the midst of ... ...

Abstract	BACKGROUND: Endpoint choice for randomized controlled trials of treatments for novel coronavirus-induced disease (COVID-19) is complex. Trials must start rapidly to identify treatments that can be used as part of the outbreak response, in the midst of considerable uncertainty and limited information. COVID-19 presentation is heterogeneous, ranging from mild disease that improves within days to critical disease that can last weeks to over a month and can end in death. While improvement in mortality would provide unquestionable evidence about the clinical significance of a treatment, sample sizes for a study evaluating mortality are large and may be impractical, particularly given a multitude of putative therapies to evaluate. Furthermore, patient states in between "cure" and "death" represent meaningful distinctions. Clinical severity scores have been proposed as an alternative. However, the appropriate summary measure for severity scores has been the subject of debate, particularly given the variable time course of COVID-19. Outcomes measured at fixed time points, such as a comparison of severity scores between treatment and control at day 14, may risk missing the time of clinical benefit. An endpoint such as time to improvement (or recovery) avoids the timing problem. However, some have argued that power losses will result from reducing the ordinal scale to a binary state of "recovered" versus "not recovered." METHODS: We evaluate statistical power for possible trial endpoints for COVID-19 treatment trials using simulation models and data from two recent COVID-19 treatment trials. RESULTS: Power for fixed time-point methods depends heavily on the time selected for evaluation. Time-to-event approaches have reasonable statistical power, even when compared with a fixed time-point method evaluated at the optimal time. DISCUSSION: Time-to-event analysis methods have advantages in the COVID-19 setting, unless the optimal time for evaluating treatment effect is known in advance. Even when the optimal time is known, a time-to-event approach may increase power for interim analyses.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #647480
Database	COVID19

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

To top

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Kategorien

Inter-library loan at ZB MED