Search

Background The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. Methods In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8–1.2 g/kg/day). The primary outcome is 90-day all-cause mortality, and other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30–25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. Conclusion Ethics approval was obtained from the King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R ). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings Trial registration: ClinicalTrials.gov Identifier: NCT04475666. Registered on July 17, 2020 https://clinicaltrials.gov/ct2/show/NCT04475666

Summary Background and aims The optimal amount of protein intake in critically ill patients is unclear. The objective of this pilot trial is to assess the feasibility of a large randomized controlled trial testing higher versus lower protein intake in critically ill patients. Methods In this pilot randomized controlled trial (REPLacing Protein via Enteral Nutrition in a Stepwise ApproacH in critically ill patients: A pilot randomized controlled trial (REPLENISH pilot trial), critically ill patients underwent 2-step screening for eligibility on ICU day 1 and 5. Patients with renal disease were excluded. Eligible patients were randomized into REPLENISH group (target protein 1.8–2.2 g kg/day) and Standard group (target protein 0.8–1.0 g/kg/day) from day 6–14 after ICU admission. Dietitians adjusted caloric and protein intake throughout the study period (Day 1–14) to maintain similar caloric targets of permissive underfeeding (40–60% of estimated energy expenditure) in both study groups. Results Of 704 patients screened at 3 centers in Saudi Arabia from May 2018 to May 2019, only 63 (8.9%) were eligible and 40 (5.7% of screened) were randomized with an average of 2 patients enrolled in the trial per month. Among eligible patients, the consenting rate was high at 89%. During the intervention period, patients in the REPLENISH group (N = 21) had a modestly higher protein intake (median of 1.30 g/kg/day (Q1 Q3: 1.11, 1.57)) than those in the standard group (median of 0.77 g/kg/day (Q1 Q3: 0.57, 1.00); P = 0.0004). Only 31.4% of patients in the whole cohort had >80% of prescribed protein. The duration of daily interruption of feeding was almost 4 h in both groups. The 90-day mortality for the patient study cohort was 20.5%. Anthropometric and muscle strength measurements were performed in less than 50% of patients. Conclusions This pilot trial highlighted several areas for improvement in the study protocol before launching a large randomized controlled trial. The restrictive eligibility criteria, the complex adjustments of protein and energy and some of the outcome measurements were identified as targets for modifications, to improve enrollment and generalizability and to enhance adherence to study interventions and measurements. Trial registration: clinicaltrials.gov identifier NCT03480555.

BackgroundDiabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data, and outcomes of critically ill patients with diabetes and Middle East Respiratory Syndrome (MERS).MethodsThis retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012–January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course, and outcomes of critically ill patients with MERS who had diabetes compared to those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality.ResultsOf the 350 critically ill patients with MERS, 171 (48.9%) had diabetes. Patients with diabetes were more likely to be older, and have comorbid conditions, compared to patients with no diabetes. They were more likely to present with respiratory failure requiring intubation, vasopressors, and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes). Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%,p ConclusionsHalf of the critically ill patients with MERS have diabetes; which is associated with more severe disease. Diabetes is an independent predictor of mortality among critically patients with MERS.

Additional file 1.

Background: Diabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data and outcomes of critically ill patients with diabetes who developed Middle East Respiratory Syndrome (MERS).Methods: This retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012-January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course and outcomes between critically ill MERS patients who had diabetes and those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality.Results: Of the 350 MERS patients, 171 (48.9%) had diabetes, were more likely to be older and have comorbid conditions. Patients with diabetes were more likely to present with respiratory failure requiring intubation, vasopressors and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes. Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%, pConclusions: Critically ill patients with diabetes constitute half of critically ill patients with MERS, presenting with more severe disease requiring mechanical ventilation compared to those who do not have diabetes. Diabetes is an independent predictor of mortality.

Background The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. Methods This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. Results Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). Conclusions In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance., In this observational study accounting for baseline and time-varying confounders, ribavirin and recombinant interferon (rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

Abstract 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.

Objectives:To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. Design:Retrospective cohort study. Setting:Patients admitted to ICUs in 14 Saudi Arabian hospitals. Patients:Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n= 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non–Middle East respiratory syndrome etiology (non–Middle East respiratory syndrome severe acute respiratory infection) (n= 222). Interventions:None. Measurements and Main Results:Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non–Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78];p< 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252];p< 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7];p= 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%;p< 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%;p= 0.003), vasopressor support (79.4% vs 55.0%;p< 0.001), and renal replacement therapy (48.8% vs 22.1%;p< 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non–Middle East respiratory syndrome severe acute respiratory infection (adjusted odds ratio, 5.87; 95% CI, 4.02–8.56;p< 0.001). Conclusions:Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.

Background Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes. Aim We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS. Methods Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012–9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale. Findings Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days. Conclusion Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.