Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

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; 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 to 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 institutional review board, 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, NCT04475666 . Registered on July 17, 2020.

Impact of Corticosteroid Therapy on ICU Patient Outcomes in Severe COVID-19 Cases: A Retrospective Cohort Study in Saudi Arabia.

BACKGROUND: The COVID-19 pandemic has presented significant challenges in clinical management, and intensive care units (ICUs) worldwide have become epicenters of high-stakes treatment decisions. Among these, corticosteroid therapy has risen as a pivotal, yet controversial, treatment modality. In Saudi Arabia, where unique demographic and health system characteristics intersect, understanding the specific effects of corticosteroids on ICU patient outcomes is not just critical but a pressing necessity in tailoring effective COVID-19 management strategies. OBJECTIVE: This study aims to elucidate the effects of corticosteroid therapy on the outcomes of severe COVID-19 patients in Saudi Arabian ICUs, providing critical insights into treatment efficacy and guiding future clinical practices. MATERIALS AND METHODS: In this cohort study, we meticulously reviewed the medical records of 1085 severe COVID-19 patients admitted to Saudi Arabian ICUs. Our analysis focused on demographic details, ICU outcomes, and the extent and implications of corticosteroid therapy. The study employed comprehensive methods for data collection, evaluation criteria, and statistical analysis, ensuring a thorough understanding of the impact of corticosteroids in this context. RESULTS: The study encompassed 1085 patients, predominantly male (74.5%, N=806), with an average age of 56 and a mean BMI of 30.07. A significant portion (72.3%, N=784) received corticosteroid therapy. These patients generally experienced longer ICU (mean 23 days) and hospital stays (mean 16 days), along with higher rates of microbiological cure (72.3%, N=648) and increased ICU discharge likelihood. Conversely, corticosteroid recipients showed higher mortality rates at ICU discharge. The statistical analysis confirmed the significance of these findings, reinforcing their importance in managing COVID-19 in ICUs. CONCLUSION: The research highlights the intricate dynamics of corticosteroid use in treating severe COVID-19 cases in ICUs. While associated with prolonged ICU stays and increased mortality, corticosteroids also correlate with higher microbiological cure rates and discharge likelihood. These insights call for careful deliberation in applying corticosteroid therapy, with implications for enhancing clinical protocols and guiding future research in severe COVID-19 treatment.

Retrospective Cohort Study on Determinants of Mechanical Ventilation Duration of COVID-19 ICU Patients.

Background In the face of the ongoing global health crisis posed by COVID-19, it becomes imperative to understand the disease's dynamics, particularly in specific regions. This study provides a detailed examination of the factors influencing mechanical ventilation (MV) duration among COVID-19 patients in an intensive care setting, focusing on a diverse patient cohort from the Al Hassa region of Saudi Arabia. The primary aim of this study was to identify key demographic factors, clinical outcomes, and comorbidities that affect the duration of MV among ICU patients with COVID-19. This understanding is crucial for enhancing patient care and informing healthcare strategies in the context of the pandemic. Methods A retrospective cohort study was conducted involving patients diagnosed with COVID-19 and admitted to the ICU in the Al Hassa region. The total number of participants was 1,259. Using a systematic sampling method, these participants were chosen to create a representative sample that reflects the prevailing treatment protocols in ICUs across these hospitals. Data encompassed patient demographics, comorbidities, clinical outcomes, and MV duration. Statistical analyses were employed to explore the associations between these variables. Results Our findings reveal a total of 1,259 participants significant associations between MV duration and various factors, including nationality, legal status, travel history, and comorbidities like heart failure and immunocompromised status. These insights are instrumental in understanding the nuances of COVID-19 management in critical care. Conclusion The study provides valuable insights into the determinants of MV duration in severe COVID-19 cases, emphasizing the need for individualized patient care approaches. It highlights the complexity of managing COVID-19 in ICU settings and underscores the importance of tailored healthcare responses to this global health challenge, particularly in the Al Hassa region.

Impact of Tracheostomy on COVID-19 ICU Patients in Saudi Arabia: A Retrospective Analysis.

Introduction The COVID-19 pandemic has prompted the development of novel medical interventions, including tracheostomy, a surgical procedure for a direct airway. This study investigates the intricacies of managing critically ill patients in the ICU, focusing on its debated utility in the global crisis. Methods The study assessed the impact of tracheostomy on COVID-19 patients at Al-Ahsa Hospital, Saudi Arabia, using a retrospective cohort design and data from electronic health records and databases. It aimed to provide insights into treatment outcomes and practices. Results The findings of this study shed light on the significant impact of tracheostomy on the course of ICU treatment for COVID-19 patients. Total number of participants were 1389. The study cohort consisted of predominantly non-pregnant individuals with an average body mass index reflective of the regional population. Among the COVID-19 patients, only a small percentage, 63 (4.5%), required tracheostomy, while the majority, 1326 (95.5%), did not undergo this procedure. Analysis of ICU outcomes revealed that a substantial proportion of patients, 223 (16.1%), achieved total cure, while the remaining patients did not. After a 28-day ICU stay, the majority of individuals, 1287 (92.7%), were discharged, while a smaller percentage remained in the ICU, with 77 (5.5%) still requiring mechanical ventilation. Notably, patients who underwent tracheostomy had a significantly longer ICU stay compared to those who did not, with an average of 59 days versus 19 days, respectively. Furthermore, the study found that tracheostomy did not significantly impact ICU discharge outcomes, including death, discharge home, and transfer to another facility. However, it did influence hospital discharge outcomes, with lower mortality rates and a higher rate of transfer to another facility among patients who underwent tracheostomy. These results provide valuable insights into the management and outcomes of critically ill COVID-19 patients in the ICU, particularly in relation to the use of tracheostomy as a treatment intervention. Conclusion The study highlights the dual benefits of tracheostomy in COVID-19 care, extending hospital stays but not increasing ICU discharge rates, emphasizing the need for tailored clinical strategies.

Body Mass Index as a Predictor of COVID-19 Severity in ICU Patients in Saudi Arabia: A Retrospective Analysis.

Introduction The global coronavirus disease 2019 (COVID-19) pandemic has prompted research into various risk factors, including the role of body mass index (BMI) in disease severity. This study specifically examines the correlation between BMI and the severity of COVID-19 among intensive care unit (ICU) patients in Saudi Arabia, addressing a gap in region-specific data. The study aims to assess the impact of BMI on the severity of COVID-19 in a Saudi Arabian ICU patient cohort, providing insights into how this relationship varies in different demographic contexts. Materials and methods Employing a retrospective cohort design, the study analyzed data from adult ICU patients in Saudi Arabia diagnosed with COVID-19. It focused on variables like BMI at admission, demographic information, and COVID-19 outcomes including severity, recovery, and mortality. Statistical analysis involved regression models, adjusting for age, gender, and comorbidities. Results Unlike global observations, the study found no significant correlation between BMI and COVID-19 severity in the Saudi Arabian context. This suggests that in this specific demographic, other factors may be more critical in determining the severity of the disease. Conclusion Our findings challenge the global consensus on BMI as a key factor in COVID-19 severity, highlighting the importance of regional differences in disease dynamics. They underscore the need for localized healthcare strategies and further research into diverse demographic factors affecting COVID-19. This study contributes to a broader understanding of the pandemic and encourages region-specific approaches in both clinical and public health spheres.

Age and Comorbidity Profiles as Predictors of Mechanical Ventilation Duration in COVID-19 ICU Patients: A Retrospective Study in Saudi Arabia.

Background The COVID-19 pandemic has highlighted the critical importance of understanding factors that impact outcomes for intensive care unit patients, especially those necessitating mechanical ventilation. This study aims to examine the influence of age and comorbidities on the duration of mechanical ventilation among COVID-19 patients in ICU settings, building on existing research that indicates the significant effects of these factors on patient outcomes. Methods A retrospective observational study was conducted involving COVID-19 patients in ICU who required mechanical ventilation. Selection criteria included ICU admission and the necessity for mechanical ventilation. Data collection focused on patient demographics, specifically age and comorbidities such as diabetes and hypertension, alongside the total duration of mechanical ventilation. The analysis utilized descriptive statistics, comparative methods, and regression modeling. Results The analysis revealed that older patients and those with certain comorbidities, notably diabetes and hypertension, typically experienced prolonged periods of mechanical ventilation. These findings are consistent with existing literature, underscoring the critical role of age and comorbidity in the management of COVID-19, in ICU patients. Conclusion This study sheds light on the significant factors influencing the duration of mechanical ventilation in COVID-19 ICU patients. The results emphasize the need for personalized treatment approaches in the ICU, particularly for older patients and those with specific comorbidities. These insights have substantial implications for clinical practice and public health, indicating the necessity for adaptable ventilation strategies and informed resource allocation. Furthermore, the findings pave the way for future research aimed at optimizing treatment protocols for diverse patient demographics in critical care settings.

Impact of Using Antiviral Therapy on COVID-19 Progression in ICU Patients: A Saudi Arabian Retrospective Analysis.

Background The COVID-19 pandemic has posed an unprecedented challenge to the global healthcare system, necessitating effective therapeutic strategies to mitigate its impact. This study investigates the significance of early antiviral therapy in the context of intensive care units (ICUs) and its potential to influence the progression and outcomes of severe COVID-19 cases. Methodology This retrospective cohort study leveraged a diverse patient population with confirmed severe COVID-19 admitted to ICUs. A total of 1,250 patients were included in the analysis, and their medical records were comprehensively reviewed. The study aimed to assess the impact of early antiviral therapy on patient outcomes, focusing on the administration of remdesivir within the first 48 hours of ICU admission. Results In a study of 1,250 COVID-19 patients, early antiviral therapy with remdesivir significantly reduced ICU admissions by 30% (N = 225) compared to standard care (N = 525). The early therapy group also exhibited a 20% lower mortality rate (N = 120) than the control group (N = 150). Demographic associations with antiviral usage were observed. Kaletra was favored by females, non-Saudi individuals, and healthcare workers, while favipiravir was associated with gender. Remdesivir and ribavirin use were linked to gender and Saudi nationality, while oseltamivir was related to gender, Saudi nationality, and body mass index. Microbiological cure rates were 15.4%, with 84.6% not achieving it. ICU outcomes included 37.7% deaths, 55.7% home discharges, and 6.6% transfers, while hospital outcomes featured 38.5% deaths, 54.4% home discharges, and 7.1% transfers. Conclusions This study presents a comprehensive analysis of COVID-19 patient demographics, antiviral medication associations, and clinical outcomes. The findings highlight the significance of tailoring treatment strategies based on patient characteristics and viral history. These insights contribute to a deeper understanding of COVID-19 management and can inform clinical decision-making and further research in this field.

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol.

BACKGROUND: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. DISCUSSION: The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.

Detection of Carbapenem-resistance in CRE by Comparative Assessment of RAPIDEC® CARBA NP and Xpert™Carba-R Assay.

Introduction: Carbapenem-resistant Enterobacteriaceae (CRE) infections resist nearly most available antimicrobials, resulting in poor clinical outcomes. Saudi Arabia has a relatively high CRE prevalence. This study aims to evaluate the sensitivity of Rapidec Carba NP test and GeneXpert Carba-R assay compared with conventional manners for detection of carbapenemase-producing Enterobacteriaceae. Methods: This is a cross-sectional study including a total of 90 CRE isolates examined at two tertiary hospitals in KSA from October 2020 to December 2021. Gram-negative Enterobacteriaceae were identified by using Vitek 2 system and were furtherly tested for imipenem and meropenem susceptibility by E- test strips, followed by Rapidec Carba NP test and the Xpert™Carba-R assay. Results: Carbapenem-resistant K. pneumoniae (78.9%) and carbapenem-resistant E. coli (14.4%) were the two most common isolates species. Colistin (98.9%) and tigecycline (88.9%) were the most effective antibiotics against CRE isolates, followed by amikacin (52.2%), gentamicin (33.3%), cotrimoxazole (15.6%), and ciprofloxacin (8.9%). blaOXA-48 was the predominant carbapenemase gene (44.4%), followed by blaNDM (32.2%). blaKPC gene was not detected. The Rapidec Carba NP and the Xpert™Carba-R demonstrated an overall sensitivity of 69.3% and 88%, respectively, in comparison to gold standard detection of meropenem and imipenem resistance by Vitek 2 system and E- test strips. Discussion: RAPIDEC® CARBA NP may be a beneficial screening test for detecting CRE, but for confirmation of the results, Xpert Carba-R assay is more sensitive, significantly lowering the turnaround time compared to reference traditional methods. The information on carbapenemase genes may be used for epidemiologic purposes and outbreak management.

Tocilizumab Outcomes in Critically Ill COVID-19 Patients Admitted to the ICU and the Role of Non-Tocilizumab COVID-19-Specific Medical Therapeutics.

BACKGROUND: Tocilizumab is a monoclonal antibody proposed to manage cytokine release syndrome (CRS) associated with severe COVID-19. Previously published reports have shown that tocilizumab may improve the clinical outcomes of critically ill patients admitted to the ICU. However, no precise data about the role of other medical therapeutics concurrently used for COVID-19 on this outcome have been published. OBJECTIVES: We aimed to compare the overall outcome of critically ill COVID-19 patients admitted to the ICU who received tocilizumab with the outcome of matched patients who did not receive tocilizumab while controlling for other confounders, including medical therapeutics for critically ill patients admitted to ICUs. METHODS: A prospective, observational, multicenter cohort study was conducted among critically ill COVID-19 patients admitted to the ICU of 14 hospitals in Saudi Arabia between 1 March 2020, and October 31, 2020. Propensity-score matching was utilized to compare patients who received tocilizumab to patients who did not. In addition, the log-rank test was used to compare the 28 day hospital survival of patients who received tocilizumab with those who did not. Then, a multivariate logistic regression analysis of the matched groups was performed to evaluate the impact of the remaining concurrent medical therapeutics that could not be excluded via matching 28 day hospital survival rates. The primary outcome measure was patients' overall 28 day hospital survival, and the secondary outcomes were ICU length of stay and ICU survival to hospital discharge. RESULTS: A total of 1470 unmatched patients were included, of whom 426 received tocilizumab. The total number of propensity-matched patients was 1278. Overall, 28 day hospital survival revealed a significant difference between the unmatched non-tocilizumab group (586; 56.1%) and the tocilizumab group (269; 63.1%) (p-value = 0.016), and this difference increased even more in the propensity-matched analysis between the non-tocilizumab group (466.7; 54.6%) and the tocilizumab group (269; 63.1%) (p-value = 0.005). The matching model successfully matched the two groups' common medical therapeutics used to treat COVID-19. Two medical therapeutics remained significantly different, favoring the tocilizumab group. A multivariate logistic regression was performed for the 28 day hospital survival in the propensity-matched patients. It showed that neither steroids (OR: 1.07 (95% CI: 0.75-1.53)) (p = 0.697) nor favipiravir (OR: 1.08 (95% CI: 0.61-1.9)) (p = 0.799) remained as a predictor for an increase in 28 day survival. CONCLUSION: The tocilizumab treatment in critically ill COVID-19 patients admitted to the ICU improved the overall 28 day hospital survival, which might not be influenced by the concurrent use of other COVID-19 medical therapeutics, although further research is needed to confirm this.

Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial.

PURPOSE: To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. METHODS: This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure (n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS. RESULTS: Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference - 1.5% (95% confidence interval [CI] - 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI - 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI - 31.92, 31.92; p = 0.55). CONCLUSIONS: Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19: The HELMET-COVID Randomized Clinical Trial.

Importance: Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective: To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants: This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions: Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures: The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results: Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance: Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04477668.

Machine learning decision tree algorithm role for predicting mortality in critically ill adult COVID-19 patients admitted to the ICU.

BACKGROUND: Coronavirus disease-19 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently a major cause of intensive care unit (ICU) admissions globally. The role of machine learning in the ICU is evolving but currently limited to diagnostic and prognostic values. A decision tree (DT) algorithm is a simple and intuitive machine learning method that provides sequential nonlinear analysis of variables. It is simple and might be a valuable tool for bedside physicians during COVID-19 to predict ICU outcomes and help in critical decision-making like end-of-life decisions and bed allocation in the event of limited ICU bed capacities. Herein, we utilized a machine learning DT algorithm to describe the association of a predefined set of variables and 28-day ICU outcome in adult COVID-19 patients admitted to the ICU. We highlight the value of utilizing a machine learning DT algorithm in the ICU at the time of a COVID-19 pandemic. METHODS: This was a prospective and multicenter cohort study involving 14 hospitals in Saudi Arabia. We included critically ill COVID-19 patients admitted to the ICU between March 1, 2020, and October 31, 2020. The predictors of 28-day ICU mortality were identified using two predictive models: conventional logistic regression and DT analyses. RESULTS: There were 1468 critically ill COVID-19 patients included in the study. The 28-day ICU mortality was 540 (36.8 %), and the 90-day mortality was 600 (40.9 %). The DT algorithm identified five variables that were integrated into the algorithm to predict 28-day ICU outcomes: need for intubation, need for vasopressors, age, gender, and PaO2/FiO2 ratio. CONCLUSION: DT is a simple tool that might be utilized in the ICU to identify critically ill COVID-19 patients who are at high risk of 28-day ICU mortality. However, further studies and external validation are still required.

Predictors of survival from Acinetobacter in Saudi Arabian intensive care units: A prospective, one-year, six-city, ten-center cohort study.

BACKGROUND: Antibiotic-resistant Acinetobacter baumannii is a continuously-emerging worldwide health crisis, with mortality rates approaching 50% in intensive care unit (ICU) patients. The objective of this study was to evaluate regional, patient-related, and organism-related predictors of survival among critically-ill patients with confirmed Acinetobacter infection. METHODS: This prospective cohort study was conducted within ten ICUs across six geographically- and climatologically-distinct cities across Saudi Arabia over 13 months. RESULTS: Of 169 patients with confirmed Acinetobacter infection enrolled in the study, 80 (47.6%) died. Survivors were statistically younger, predominantly male, more likely to be admitted for trauma, less likely to have hypertension, diabetes, or have undergone hemodialysis, and more likely to have been treated with antibiotics prior to having a positive culture for Acinetobacter, but less likely to have received an aminoglycoside. Survivors also had lower baseline APACHE II and SOFA scores and were infected with stains of Acinetobacter that had less meropenem- or colistin-resistance. Multivariate analysis identified the following independent predictors of survival: younger age, lower ICU-day#1 APACHE-II and ICU-day#3 SOFA scores, being admitted for trauma, and having no history of hemodialysis. CONCLUSIONS: Patient-related factors outweigh regional and hospital-related factors as predictors of survival among critically-ill patients with Acinetobacter infection.

Helmet noninvasive ventilation for COVID-19 patients (Helmet-COVID): statistical analysis plan for a randomized controlled trial.

BACKGROUND: Noninvasive respiratory support is frequently needed for patients with acute hypoxemic respiratory failure due to coronavirus disease 19 (COVID-19). Helmet noninvasive ventilation has multiple advantages over other oxygen support modalities but data about effectiveness are limited. METHODS: In this multicenter randomized trial of helmet noninvasive ventilation for COVID-19 patients, 320 adult ICU patients (aged ≥14 years or as per local standards) with suspected or confirmed COVID-19 and acute hypoxemic respiratory failure (ratio of arterial oxygen partial pressure to fraction of inspired oxygen < 200 despite supplemental oxygen with a partial/non-rebreathing mask at a flow rate of 10 L/min or higher) will be randomized to helmet noninvasive ventilation with usual care or usual care alone, which may include mask noninvasive ventilation, high-flow nasal oxygen, or standard oxygen therapy. The primary outcome is death from any cause within 28 days after randomization. The trial has 80% power to detect a 15% absolute risk reduction in 28-day mortality from 40 to 25%. The primary outcome will be compared between the helmet and usual care group in the intention-to-treat using the chi-square test. Results will be reported as relative risk  and 95% confidence interval. The first patient was enrolled on February 8, 2021. As of August 1, 2021, 252 patients have been enrolled from 7 centers in Saudi Arabia and Kuwait. DISCUSSION: We developed a detailed statistical analysis plan to guide the analysis of the Helmet-COVID trial, which is expected to conclude enrollment in November 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT04477668 . Registered on July 20, 2020.

Incidence, outcomes, and predictors of Acinetobacter infection in Saudi Arabian critical care units.

BACKGROUND: Acinetobacter is an increasingly-problematic organism, especially in intensive care units (ICUs). In this study, we compared its incidence, outcomes, and predictors spanning eight ICUs in five geographically and climatologically-diverse cities in Saudi Arabia. METHODS: Geographic, climatologic, hospital-related, and patient-related factors were collected prospectively on 3179 patients admitted to eight Saudi ICUs from June 2018 through June 2019. These data then underwent both bivariable and multivariable analysis, the latter vis hierarchical logistic regression to identify predictors of clinically-manifest Acinetobacter infection. RESULTS: Overall incidence of Acinetobacter infection was 3.9% (n = 124). Of these 124 infections, 122 (98.4%) were cultured as A. baumannii. Incidence ranged from 1.0 to 7.9% across the eight ICUs. On bivariable analysis, incident Acinetobacter infection was more common in university and military hospitals, in hospitals with more total beds and ICU isolation rooms, and in 2018 versus 2019, incidence steadily declining over the 13 study months. Mechanically-ventilated patients had ten-fold increased odds of infection. Adjusted (multivariable) analysis revealed the risk of clinically-manifest Acinetobacter infection to increase the longer patients were on mechanical ventilation. Increased risk also existed at certain hospitals over others, especially in university-affiliated and military hospitals, larger hospitals with more isolation rooms, and hospitals with fewer ICU beds. CONCLUSION: In our study of eight ICUs across Saudi Arabia, inter-hospital differences did appear to account for inter-hospital differences in Acinetobacter incidence rates. Patients requiring mechanical ventilation for longer periods of time were particularly at risk.

Helmet Non-Invasive Ventilation for COVID-19 Patients (Helmet-COVID): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Non-invasive ventilation (NIV) delivered by helmet has been used for respiratory support of patients with acute hypoxaemic respiratory failure due to COVID-19 pneumonia. The aim of this study was to compare helmet NIV with usual care versus usual care alone to reduce mortality. METHODS AND ANALYSIS: This is a multicentre, pragmatic, parallel randomised controlled trial that compares helmet NIV with usual care to usual care alone in a 1:1 ratio. A total of 320 patients will be enrolled in this study. The primary outcome is 28-day all-cause mortality. The primary outcome will be compared between the two study groups in the intention-to-treat and per-protocol cohorts. An interim analysis will be conducted for both safety and effectiveness. ETHICS AND DISSEMINATION: Approvals are obtained from the institutional review boards of each participating institution. Our findings will be published in peer-reviewed journals and presented at relevant conferences and meetings. TRIAL REGISTRATION NUMBER: NCT04477668.

Critically ill patients with diabetes and Middle East respiratory syndrome: a multi-center observational study.

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 and 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 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. RESULTS: Of 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 < 0.0001). Multivariable regression analysis showed that diabetes was an independent risk factor for 90-day mortality (odds ratio, 2.09; 95% confidence interval, 1.18-3.72). CONCLUSIONS: Half 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.

Treatment of Middle East respiratory syndrome with a combination of lopinavir/ritonavir and interferon-ß1b (MIRACLE trial): statistical analysis plan for a recursive two-stage group sequential randomized controlled trial.

The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-ß1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-ß1b 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.

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

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-ß1a; none received rIFN-ß1b). 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-ß1a) 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.