We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples ...from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
AbstractThe objective of this systematic review was to know the role of the bid examination committee in administrative contracting in Saudi Arabia and United Arab Emirates. Following the PRISMA ...protocol, we conducted a review of papers published in 3 databases (Google scholar, JSTOR, Researchgate). It was conducted in September and October 2023. Moreover, studies that addressed the bid examination and published since 2000 were included. The focus was made upon comparing the role of bid examination committee in administrative contracting in KSA and UAE. From the initial 543 studies reviewed, 40 met the inclusion criteria. The principles of the bid examination committee have been considered by the relatively small number of studies included in the review. We did find a variety of researchers from different countries examining the phenomenon, often using qualitative approaches to explore the topic. Although the link between bid examination committee and government projects in Saudi Arabia and UAE has been qualitatively and quantitatively found, the link between bid examination committee and administrative contracting remains lacking.
Background
Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure ...to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto‐Abs) to type I IFNs were reported as a risk factor for life‐threatening COVID‐19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS).
Methods
We evaluated the prevalence of type I IFN auto‐Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo‐controlled clinical trial for treatment with IFN‐β1b and lopinavir‐ritonavir (MIRACLE trial). Samples were tested for type I IFN auto‐Abs using a multiplex particle‐based assay.
Results
Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto‐Abs for at least one subtype of type I IFNs. Auto‐Abs positive patients were not different from auto‐Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto‐Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto‐Abs negative patients. The effect of treatment with IFN‐β1b and lopinavir‐ritonavir did not significantly differ between the two groups.
Conclusion
This study demonstrates the presence of type I IFN auto‐Abs in hospitalized patients with MERS.
It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized ...clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission.
The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality.
This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018.
ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.
The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant ...interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.
The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody ...response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1-3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.
The demand for critical care beds is increasing out of proportion to bed availability. As a result, some critically ill patients are kept in the Emergency Department (ED boarding) awaiting bed ...availability. The aim of our study is to examine the impact of boarding in the ED on the outcome of patients admitted to the Intensive Care Unit(ICU).
This was a retrospective analysis of ICU data collected prospectively at King Abdulaziz Medical City, Riyadh from ED between January 2010 and December 2012 and all patients admitted during this time were evaluated for their duration of boarding. Patients were stratified into three groups according to the duration of boarding from ED. Those admitted less than 6 h were classified as Group I, between 6 and 24 h, Group II and more than 24 h as Group III. We carried out multivariate analysis to examine the independent association of boarding time with the outcome adjusting for variables like age, sex, APACHE, Mechanical ventilation, Creatinine, Platelets, INR.
During the study period, 940 patients were admitted from the ED to ICU, amongst whom 227 (25%) were admitted to ICU within 6 h, 358 (39%) within 6-24 h and 355 (38%) after 24 h. Patients admitted to ICU within 6 h were younger 48.7 ± 22.2(group I) years, 50.6 ± 22.6 (group II), 58.2 ± 20.9 (group III) (P = 0.04)with less mechanical ventilation duration5.9 ± 8.9 days (Group I), 6.5 ± 8.1 (Group II) and 10.6 ± 10.5 (Group III), P = 0.04. There was a significant increase in hospital mortality 51(22.5), 104(29.1), 132(37.2), P = 0.0006) and the ICU length of stay(LOS) 9.55 days (Group I), 9.8 (Group II) and 10.6 (Group III), (P = 0.002) with increase in boarding duration. In addition, the delay in admission was an independent risk factor for ICU mortality(OR for group III vs group I is 1.90, P = 0.04) and hospital mortality(OR for group III vs Group I is 2.09, P = 0.007).
Boarding in the ED is associated with higher mortality. This data highlights the importance of this phenomenon and suggests the need for urgent measures to reduce boarding and to improve patient flow.
This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality.
This was a ...post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4-7 (at least active standing), 1-3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables.
Of 1708 patients, only 85 (5.0%) had early mobility level 4-7 and 356 (20.8%) level 1-3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4-7 and 1-3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4-7 group, 7/348 (2.0%) patients in mobility 1-3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4-7 and 1-3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio aHR 1.19, 95% confidence interval CI 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4-7 and 1-3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p < 0.0001, respectively).
Only a small proportion of critically ill patients with an expected ICU stay ≥ 72 h were mobilized early. Early mobility was associated with reduced mortality, but not with different incidence of deep-vein thrombosis. This association does not establish causality, and randomized controlled trials are required to assess whether and to what extent this association is modifiable.
The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).
Abstract Introduction The objective of this study was to examine the effect of implementing a clinical practice guidelines–based management protocol on the outcome of patients with severe traumatic ...brain injury (TBI). Methods We carried out a pre-post guideline implementation study using previously collected data in the Intensive Care Unit (ICU). All patients older than 12 years with severe TBI, defined as a Glasgow Coma Scale score of 8 or less, from March 1999 to January 2001 (control group) and from February 2001 to December 2006 (protocol group) were identified and included in this study. Patients in the protocol group were managed using a clinical practice guidelines–based management protocol, derived from the guidelines published by the Brain Trauma Foundation. Primary outcome was hospital mortality, whereas the secondary outcome was ICU mortality. To assess whether the ICU protocol might have led to an increase in the number of surviving patients with severe disability, we examined the association of the protocol use and the need for tracheostomies, mechanical ventilation duration, and ICU and hospital length of stay (LOS) among survivors. Results During the study period, a total of 434 patients met the inclusion criteria. After adjustment for several prognostic factors, the use of protocol was independently associated with a significant reduction in hospital and ICU mortality (odds ratio, 0.45; 95% confidence interval, 0.24-0.86; and odds ratio, 0.47; 95% confidence interval, 0.23-0.96, respectively). The use of the protocol was not associated with an increase in the need for tracheostomies, mechanical ventilation duration, ICU LOS, and hospital LOS. Conclusion The protocol implementation was associated with a reduction in hospital and ICU mortality. This improvement was not associated with an increase in the frequency of tracheostomies and in ICU or hospital LOS, suggesting that the improved survival was not associated with the increased number of surviving patients with severe disability and that the functional status might have also improved.
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