Publications by authors named "Farah al-Beidh"
Rationale: Heterogeneity of the host response within sepsis, acute respiratory distress syndrome (ARDS) and more widely critical illness, limits discovery and targeting of immunomodulatory therapies. Clustering approaches using clinical and circulating biomarkers have defined hyper-inflammatory and hypo-inflammatory subphenotypes in ARDS associated with differential treatment response. It is unknown if similar subphenotypes exist in sepsis populations where leucocyte transcriptomic-defined subphenotypes have been reported.
View Article and Find Full Text PDFArticle Synopsis
- The SuDDICU trial aims to evaluate the effects of selective decontamination of the digestive tract (SDD) on outcomes for ventilated patients in ICUs, focusing on whether it reduces hospital mortality and affects antibiotic resistance.
- This international study involves 19 ICUs in Australia and 10 in Canada and the UK, recruiting 15,000 to 17,000 patients over two 12-month trial periods, comparing SDD plus standard care against standard care alone.
- Key primary and secondary outcomes include all-cause hospital mortality, duration of ventilation, ICU and hospital stay, incidence of new infections, and the development of antibiotic resistance, with recruitment starting in 2017.
Article Synopsis
- The study aimed to evaluate the effectiveness of simvastatin in critically ill Covid-19 patients compared to a control group not receiving statins.
- A total of 2684 patients were analyzed, showing a median of 11 organ support-free days in the simvastatin group versus 7 in the control group, with a high probability indicating simvastatin’s potential superiority.
- However, the study was halted due to decreasing Covid-19 cases, and while simvastatin had some benefits, it also led to more reported serious adverse effects, such as elevated liver enzymes.
Importance: The efficacy of vitamin C for hospitalized patients with COVID-19 is uncertain.
Objective: To determine whether vitamin C improves outcomes for patients with COVID-19.
Design, Setting, And Participants: Two prospectively harmonized randomized clinical trials enrolled critically ill patients receiving organ support in intensive care units (90 sites) and patients who were not critically ill (40 sites) between July 23, 2020, and July 15, 2022, on 4 continents.
Article Synopsis
- Overactivation of the renin-angiotensin system (RAS) could lead to worse outcomes for COVID-19 patients, prompting a study to see if ACE inhibitors or ARBs could help.
- In a clinical trial with 721 patients, participants were randomly assigned to receive either an ACE inhibitor, an ARB, or no RAS inhibitor to evaluate their effects on patient recovery.
- Results showed no significant improvement in organ support-free days among the treatment groups compared to the control, leading to the discontinuation of enrollment due to safety concerns.
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.
Article Synopsis
- Tools to detect SARS-CoV-2 variants are crucial for public health and the development of vaccines and therapies.
- A new allele-specific probe PCR (ASP-PCR) method was created to efficiently identify virus variants, especially in samples with low viral loads or poor RNA quality.
- ASP-PCR demonstrated higher accuracy than next-generation sequencing (NGS) in certain conditions and yielded nearly identical results to NGS, making it a strong complementary method for screening SARS-CoV-2.
Article Synopsis
- The study aimed to assess whether antiplatelet therapy, specifically aspirin or P2Y12 inhibitors, improves outcomes for critically ill COVID-19 patients compared to no treatment.
- Involved a total of 1557 adult patients across 105 sites in 8 countries, monitored over 90 days, with patients randomly assigned to receive either aspirin, a P2Y12 inhibitor, or no treatment.
- Findings indicated that both aspirin and P2Y12 inhibitor groups showed similar efficacy in terms of organ support-free days, meeting criteria for equivalence in their effectiveness.
Unlabelled: This is the largest study describing the role of P450 epoxygenase metabolites in septic shock in humans and suggests a novel therapeutic target.
Objectives: Oxylipins are oxidative breakdown products of cell membrane fatty acids. Animal models have demonstrated that oxylipins generated by the P450 epoxygenase pathway may be implicated in septic shock pathology.
Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.
View Article and Find Full Text PDFArticle Synopsis
- The study aimed to assess the effectiveness of convalescent plasma in improving outcomes for critically ill COVID-19 patients, as previous evidence was unclear.
- A total of 4,763 adults were enrolled in a trial, with 1,084 receiving convalescent plasma and 916 not receiving it, within 48 hours after randomization.
- The primary outcomes measured were organ support-free days and survival rates, using a Bayesian statistical model to evaluate the results and determine the efficacy of the treatment.
Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.
N Engl J Med
August 2021
Article Synopsis
- A clinical trial investigated whether therapeutic-dose anticoagulation could improve outcomes for critically ill patients with severe Covid-19 compared to standard thromboprophylaxis.
- The study found no significant difference in organ support-free days between the two groups, with the anticoagulation group showing a median of 1 day compared to 4 days for the usual-care group.
- The trial was halted due to a high probability of futility, with similar hospital discharge survival rates and a slightly higher occurrence of major bleeding in the anticoagulation group.
Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19.
N Engl J Med
August 2021
Background: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.
Methods: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis.
Purpose: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19).
Methods: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days.
Background: Convalescent plasma containing neutralizing antibody to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is under investigation for coronavirus disease 2019 (COVID-19) treatment. We report diverse virological characteristics of UK intensive care patients enrolled in the Immunoglobulin Domain of the REMAP-CAP randomized controlled trial that potentially influence treatment outcomes.
Methods: SARS-CoV-2 RNA in nasopharyngeal swabs collected pretreatment was quantified by PCR.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.
N Engl J Med
April 2021
Background: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.
Methods: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control).
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.
There is broad interest in improved methods to generate robust evidence regarding best practice, especially in settings where patient conditions are heterogenous and require multiple concomitant therapies. Here, we present the rationale and design of a large, international trial that combines features of adaptive platform trials with pragmatic point-of-care trials to determine best treatment strategies for patients admitted to an intensive care unit with severe community-acquired pneumonia. The trial uses a novel design, entitled "a randomized embedded multifactorial adaptive platform.
View Article and Find Full Text PDFArticle Synopsis
- Myocardial dysfunction is prevalent in sepsis, but a study called the LeoPARDS trial found that the inodilator levosimendan does not improve organ dysfunction or reduce mortality in septic shock patients.
- The research measured cardiac biomarkers and inflammatory mediators in patients to assess the drug's effects, revealing no benefits in reducing the SOFA score or 28-day mortality rates.
- Specifically, patients with high NT-proBNP who received levosimendan showed worse SOFA scores compared to those on placebo, indicating that levosimendan added to standard care does not enhance outcomes in septic patients with cardiac dysfunction.
Rationale: There remains uncertainty about the role of corticosteroids in sepsis with clear beneficial effects on shock duration, but conflicting survival effects. Two transcriptomic sepsis response signatures (SRSs) have been identified. SRS1 is relatively immunosuppressed, whereas SRS2 is relatively immunocompetent.
View Article and Find Full Text PDFArticle Synopsis
- Levosimendan is a drug that may help patients with sepsis by improving organ function, and a clinical trial was conducted to test its effectiveness compared to a placebo.
- The study included 516 patients, with no significant differences found in mean organ dysfunction scores or 28-day mortality rates between the levosimendan and placebo groups.
- However, patients receiving levosimendan had a lower success rate in weaning off mechanical ventilation and experienced more cases of a specific heart rhythm issue (supraventricular tachyarrhythmia) compared to those receiving placebo.
Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells.
View Article and Find Full Text PDFCD44 is a polymorphic transmembrane glycoprotein that binds hyaluronan and growth factors. Multiple isoforms of the protein can be generated by alternative splicing but little is known about the expression and function of these isoforms in normal development and differentiation. We have investigated the expression of CD44 during normal prostate epithelial cell differentiation.
View Article and Find Full Text PDFLigand-induced gene activation by nuclear receptors involves the recruitment of coactivators to hormone bound receptors. Recent results have shown that RAP250, also termed as ASC-2/PRIP/TRBP/NRC/AIB3, plays a critical role as a coactivator of nuclear receptors. In this study, we have determined the genomic organization of the human RAP250 gene in order to identify the promoter region.
View Article and Find Full Text PDF