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.

Ultrasound surveillance for deep venous thrombosis and subsequent venous thromboembolism in adults with trauma: A systematic review and meta-analysis.

BACKGROUND: Studies have shown routine ultrasound surveillance (RUSS) will facilitate deep vein thrombosis (DVT) detection in patients with trauma and reduce the subsequent incidence of pulmonary embolism (PE); however, the findings were inconsistent. In adults with trauma at a high risk of venous thromboembolism, this systematic review and meta-analysis compared RUSS outcomes with those of "no RUSS." METHODS: Three databases were screened for relevant articles from inception to October 18, 2021. Randomized controlled trials (RCTs) and observational studies comparing RUSS with no RUSS were included. We used relative risks (RRs), odds ratios (ORs), and mean differences to pool effect estimates for dichotomous and continuous outcomes. The cochrane risk of bias or the risk of bias in non-randomized studies of interventions were used to assess bias risk. The grading of recommendations, assessment, development, and evaluation framework assessed the certainty of the evidence. FINDINGS: Out of 1685 articles, 5 met the inclusion criteria (RCT: 1; observational studies: 4). Observational studies suggested RUSS is associated with higher odds of DVT detection (OR, 4.87; 95% confidence interval [CI], 3.13-7.57; very low certainty). Whereas higher risks of DVT were associated with RUSS in the RCT (distal DVT: RR, 15.48; 95% CI, 7.62-31.48; low certainty, and proximal DVT: RR, 2.37; 95% CI, 1.04-5.39; very low certainty). Reduced odds of PE risk were observed with the RUSS (OR, 0.47; 95% CI, 0.24-0.91; very low certainty). Observational studies indicated that RUSS had an uncertain effect on mortality (OR, 0.46; 95% CI, 0.06-3.49). In the RCT, times to proximal and distal DVT diagnoses were shorter with RUSS (proximal DVT, mean difference 2.25 days shorter [95% CI, 5.74-1.24]; distal DVT, mean differences 1.56 days shorter [95% CI, 4.22-1.12]; very low certainty for both). Increasing bleeding risk was not linked to the RUSS group (RR, 1.24; 95% CI, 0.31-4.92). INTERPRETATION: The RUSS efficacy in adults with trauma at high risk for venous thromboembolism showed that it increases DVT detection, decreases PE incidence, and shortens the time to DVT diagnosis, with an uncertain impact on mortality. The evidence is low or very low in certainty because of bias, inconsistency, imprecision, and indirectness.

Saudi Critical Care Society clinical practice guidelines on the prevention of venous thromboembolism in adults with trauma: reviewed for evidence-based integrity and endorsed by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

BACKGROUND: To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings. METHODS: The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs). RESULTS: The panel issued 12 clinical practice recommendations-one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate-high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention. CONCLUSION: The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers.

Association of early mobility with the incidence of deep-vein thrombosis and mortality among critically ill patients: a post hoc analysis of PREVENT trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: 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).

Prophylactic Inferior Vena Cava Filters for Venous Thromboembolism in Adults With Trauma: An Updated Systematic Review and Meta-Analysis.

Background: Trauma is an independent risk factor for venous thromboembolism (VTE). Due to contraindications or delay in starting pharmacological prophylaxis among trauma patients with a high risk of bleeding, the inferior vena cava (IVC) filter has been utilized as alternative prevention for pulmonary embolism (PE). Albeit, its clinical efficacy has remained uncertain. Therefore, we performed an updated systematic review and meta-analysis on the effectiveness and safety of prophylactic IVC filters in severely injured patients. Methods: Three databases (MEDLINE, EMBASE, and Cochrane) were searched from August 1, 2012, to October 27, 2021. Independent reviewers performed data extraction and quality assessment. Relative risk (RR) at 95% confidence interval (CI) pooled in a randomized meta-analysis. A parallel clinical practice guideline committee assessed the certainty of evidence using the GRADE approach. The outcomes of interest included VTE, PE, deep venous thrombosis, mortality, and IVC filter complications. Results: We included 10 controlled studies (47 140 patients), of which 3 studies (310 patients) were randomized controlled trials (RCTs) and 7 were observational studies (46 830 patients). IVC filters demonstrated no significant reduction in PE and fatal PE (RR, 0.27; 95% CI, 0.06-1.28 and RR, 0.32; 95% CI, 0.01-7.84, respectively) by pooling RCTs with low certainty. However, it demonstrated a significant reduction in the risk of PE and fatal PE (RR, 0.25; 95% CI, 0.12-0.55 and RR, 0.09; 95% CI, 0.011-0.81, respectively) by pooling observational studies with very low certainty. IVC filter did not improve mortality in both RCTs and observational studies (RR, 1.44; 95% CI, 0.86-2.43 and RR, 0.63; 95% CI, 0.3-1.31, respectively). Conclusion: In trauma patients, moderate risk reduction of PE and fatal PE was demonstrated among observational data but not RCTs. The desirable effect is not robust to outweigh the undesirable effects associated with IVC filter complications. Current evidence suggests against routinely using prophylactic IVC filters.

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.

Incidence of Bacterial and Fungal Secondary Infections in COVID-19 Patients Admitted to the ICU.

Purpose: Secondary infections have been observed among coronavirus disease 2019 (COVID-19) patients, especially in the intensive care unit (ICU) setting, which is associated with worse clinical outcomes. The current study aimed to investigate the incidence, common pathogens, and outcome of bacterial and fungal secondary infections among ICU patients with COVID-19. Methods: A retrospective chart review of all patients admitted to the ICU at King Fahd Hospital of the University in Saudi Arabia. All adult patients aged ≥18 admitted in the ICU for ≥48 hours with positive COVID-19 reverse transcription-polymerase chain reaction test during the period between March 2020 till September 2021 were included. Results: Out of 314 critically ill patients, 133 (42.4%) developed secondary infections. The incidence of secondary bacterial infection was 32.5% with Pseudomonas aeruginosa (n = 34), Acinetobacter baumannii (n = 33), and Klebsiella pneumoniae (n = 17) being the predominant pathogens, while secondary fungal infection was 25.2% mainly caused by Candida albicans (n = 43). Invasive mechanical ventilation was significantly associated with the development of secondary bacterial infections (odds ratio [OR] = 17.702, 95% confidence interval [CI] 7.842-39.961, p < 0.001) and secondary fungal infections (OR = 12.914, 95% CI 5.406-30.849, p < 0.001). Mortality among patients with secondary infections was 69.2% (n = 92). Secondary infections were associated with longer hospital and ICU stays with a median of 25 days (interquartile range [IQR] 17-42) and 19 days (IQR 13-32), respectively. Conclusion: Bacterial and fungal secondary infections are common among COVID-19 patients admitted to the ICU with a predominance of gram-negative bacteria and Candida species. The development of secondary infections was significantly associated with invasive mechanical ventilation. Poor clinical outcomes have been observed, demonstrated with a prolonged hospital and ICU stays and higher mortality.

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.

Prevalence, Causes, and Adverse Clinical Impact of Delayed Presentation of Non-COVID-19-Related Emergencies during the COVID-19 Pandemic: Findings from a Multicenter Observational Study.

Objective: The coronavirus disease (COVID-19) pandemic has disrupted healthcare systems worldwide, resulting in decreased and delayed hospital visits of patients with non-COVID-19-related acute emergencies. We evaluated the impact of the COVID-19 pandemic on the presentation and outcomes of patients with non-COVID-19-related medical and surgical emergencies. Method: All non-COVID-19-related patients hospitalized through emergency departments in three tertiary care hospitals in Saudi Arabia and Bahrain in June and July 2020 were enrolled and categorized into delayed and non-delayed groups (presentation ≥/=24 or <24 h after onset of symptom). Primary outcome was the prevalence and cause of delayed presentation; secondary outcomes included comparative 28-day clinical outcomes (i.e., 28-day mortality, intensive care unit (ICU) admission, invasive mechanical ventilation, and acute surgical interventions). Mean, median, and IQR were used to calculate the primary outcomes and inferential statistics including chi-square/Fisher exact test, t-test where appropriate were used for comparisons. Stepwise multivariate regression analysis was performed to identify the factors associated with delay in seeking medical attention. Results: In total, 24,129 patients visited emergency departments during the study period, compared to 48,734 patients in the year 2019. Of the 256 hospitalized patients with non-COVID-19-related diagnoses, 134 (52%) had delayed presentation. Fear of COVID-19 and curfew-related restrictions represented 46 (34%) and 25 (19%) of the reasons for delay. The 28-day mortality rates were significantly higher among delayed patients vs. non-delayed patients (n = 14, 10.4% vs. n = 3, 2.5%, OR: 4.628 (CI: 1.296−16.520), p = 0.038). Conclusion: More than half of hospitalized patients with non-COVID-19-related diagnoses had delayed presentation to the ED where mortality was found to be significantly higher in this group. Fear of COVID-19 and curfew restrictions were the main reasons for delaying hospital visit.

The effect of intermittent pneumatic compression on deep-vein thrombosis and ventilation-free days in critically ill patients with heart failure.

There are contradictory data regarding the effect of intermittent pneumatic compression (IPC) on the incidence of deep-vein thrombosis (DVT) and heart failure (HF) decompensation in critically ill patients. This study evaluated the effect of adjunctive use of IPC on the rate of incident DVT and ventilation-free days among critically ill patients with HF. In this pre-specified secondary analysis of the PREVENT trial (N = 2003), we compared the effect of adjunctive IPC added to pharmacologic thromboprophylaxis (IPC group), with pharmacologic thromboprophylaxis alone (control group) in critically ill patients with HF. The presence of HF was determined by the treating teams according to local practices. Patients were stratified according to preserved (≥ 40%) versus reduced (< 40%) left ventricular ejection fraction, and by the New York Heart Association (NYHA) classification. The primary outcome was incident proximal lower-limb DVT, determined with twice weekly venous Doppler ultrasonography. As a co-primary outcome, we evaluated ventilation-free days as a surrogate for clinically important HF decompensation. Among 275 patients with HF, 18 (6.5%) patients had prevalent proximal lower-limb DVT (detected on trial day 1 to 3). Of 257 patients with no prevalent DVT, 11/125 (8.8%) patients in the IPC group developed incident proximal lower-limb DVT compared to 6/132 (4.5%) patients in the control group (relative risk, 1.94; 95% confidence interval, 0.74-5.08, p = 0.17). There was no significant difference in ventilator-free days between the IPC and control groups (median 21 days versus 25 days respectively, p = 0.17). The incidence of DVT with IPC versus control was not different across NYHA classes (p value for interaction = 0.18), nor across patients with reduced and preserved ejection fraction (p value for interaction = 0.15). Ventilator-free days with IPC versus control were also not different across NYHA classes nor across patients with reduced or preserved ejection fraction. In conclsuion, the use of adjunctive IPC compared with control was associated with similar rate of incident proximal lower-limb DVT and ventilator-free days in critically ill patients with HF.Trial registration: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013, https://clinicaltrials.gov/ct2/show/study/NCT02040103 ) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).

Machine learning model for predicting the length of stay in the intensive care unit for Covid-19 patients in the eastern province of Saudi Arabia.

The COVID-19 virus has spread rapidally throughout the world. Managing resources is one of the biggest challenges that healthcare providers around the world face during the pandemic. Allocating the Intensive Care Unit (ICU) beds' capacity is important since COVID-19 is a respiratory disease and some patients need to be admitted to the hospital with an urgent need for oxygen support, ventilation, and/or intensive medical care. In the battle against COVID-19, many governments utilized technology, especially Artificial Intelligence (AI), to contain the pandemic and limit its hazardous effects. In this paper, Machine Learning models (ML) were developed to help in detecting the COVID-19 patients' need for the ICU and the estimated duration of their stay. Four ML algorithms were utilized: Random Forest (RF), Gradient Boosting (GB), Extreme Gradient Boosting (XGBoost), and Ensemble models were trained and validated on a dataset of 895 COVID-19 patients admitted to King Fahad University hospital in the eastern province of Saudi Arabia. The conducted experiments show that the Length of Stay (LoS) in the ICU can be predicted with the highest accuracy by applying the RF model for prediction, as the achieved accuracy was 94.16%. In terms of the contributor factors to the length of stay in the ICU, correlation results showed that age, C-Reactive Protein (CRP), nasal oxygen support days are the top related factors. By searching the literature, there is no published work that used the Saudi Arabia dataset to predict the need for ICU with the number of days needed. This contribution is hoped to pave the path for hospitals and healthcare providers to manage their resources more efficiently and to help in saving lives.

Bacterial and Fungal Coinfection in Critically Ill COVID-19 Cases and Predictive Role of Procalcitonin During the First Wave at an Academic Health Center.

BACKGROUND: Coinfection at various sites can complicate the clinical course of coronavirus disease of 2019 (COVID-19) patients leading to worse prognosis and increased mortality. We aimed to investigate the occurrence of coinfection in critically ill COVID-19 cases, and the predictive role of routinely tested biomarkers on admission for mortality. METHODS: This is a retrospective study of all SARS-CoV-2-infected cases, who were admitted to King Fahad Hospital of the University between March 2020 and December 2020. We reviewed the data in the electronic charts in the healthcare information management system including initial presentation, clinical course, radiological and laboratory findings and reported all significant microbiological cultures that indicated antimicrobial therapy. The mortality data were reviewed for severely ill patients who were admitted to critical care units. RESULTS: Of 1091 admitted patients, there were 70 fatalities (6.4%). 182 COVID-19 persons were admitted to the critical care service, of whom 114 patients (62.6%) survived. The in-hospital mortality was 13.4%. Coinfection was noted in 67/68 non-survivors, and Gram-negative pathogens (Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumanni) represented more than 50% of the etiological agents. We noted that the serum procalcitonin on admission was higher for non-survivors (Median = 1.6 ng/mL ± 4.7) than in survivors (Median = 0.2 ng/mL ± 4.2) (p ≤ 0.05). CONCLUSION: Coinfection is a serious complication for COVID-19 especially in the presence of co-morbidities. High levels of procalcitonin on admission may predict non-survival in critically ill cases in whom bacterial or fungal co-infection is likely.

Ketamine administration for acute painful sickle cell crisis: A randomized controlled trial.

OBJECTIVE: The objective was to evaluate the efficacy and safety of single-dose ketamine infusion in adults with sickle cell disease (SCD) who presented with acute sickle vasoocclusive crisis (VOC). METHODS: This study was a parallel-group, prospective, randomized, double-blind, pragmatic trial. Participants were randomized to receive a single dose of either ketamine or morphine, infused over 30 min. Primary outcome was mean difference in the numerical pain rating scale (NPRS) score over 2 h. NPRS was recorded every 30 min for a maximum of 180 min and secondary outcomes were cumulative dose of opioids, emergency department (ED) length of stay, hospital admission, change in vital signs, and drug-related side effects. Authors performed the analysis using intention-to-treat principle. RESULT: A total of 278 adults with SCD and who presented with acute sickle VOC participated in this trial. A total of 138 were allocated to the ketamine group. Mean (±standard deviation [SD]) NPRS scores over 2 h were 5.7 (±2.13) and 5.6 (±1.90) in the ketamine and morphine groups. The ketamine group received significantly lower cumulative doses of morphine during their ED stay (mean ± SD = 4.5 ± 4.6 mg) than of the morphine group (mean ± SD = 8.5 ± 7.55 mg). Both groups had similar rates of hospital admission: 6.3% in the ketamine group had drug-related side effects compared to 2.2% in the morphine group. CONCLUSION: Early use of ketamine in adults with VOC resulted in a meaningful reduction in pain scores over a 2-h period and reduced the cumulative morphine dose in the ED with no significant drug-related side effects in the ketamine-treated group.

Cough Sound Detection and Diagnosis Using Artificial Intelligence Techniques: Challenges and Opportunities.

Coughing is a common symptom of several respiratory diseases. The sound and type of cough are useful features to consider when diagnosing a disease. Respiratory infections pose a significant risk to human lives worldwide as well as a significant economic downturn, particularly in countries with limited therapeutic resources. In this study we reviewed the latest proposed technologies that were used to control the impact of respiratory diseases. Artificial Intelligence (AI) is a promising technology that aids in data analysis and prediction of results, thereby ensuring people's well-being. We conveyed that the cough symptom can be reliably used by AI algorithms to detect and diagnose different types of known diseases including pneumonia, pulmonary edema, asthma, tuberculosis (TB), COVID19, pertussis, and other respiratory diseases. We also identified different techniques that produced the best results for diagnosing respiratory disease using cough samples. This study presents the most recent challenges, solutions, and opportunities in respiratory disease detection and diagnosis, allowing practitioners and researchers to develop better techniques.

Predictors of Illness Severity in COVID-19 Cases in Saudi Arabia.

PURPOSE: Multiple studies worldwide have reported the clinical and epidemiological features of coronavirus disease 2019 (COVID-19), with limited reports from the Middle East. This study describes the clinical and epidemiological features of COVID-19 cases in the Eastern Province of Saudi Arabia and identified factors associated with the severity of illness. PATIENTS AND METHODS: This was an observational study of 341 COVID-19 cases. These cases were reported in the first three months after the first case in the country was identified. Clinical and demographic data were analyzed and described to identify the effects of age, sex, and ethnicity on illness severity. In addition, the duration of viral shedding and cycle threshold (Ct) values of real-time PCR were evaluated as predictors of severity. RESULTS: The median age was 45 years. Males were twice as likely to be infected than females (p <0.0001). The duration of viral shedding ranged from 9 to 36 days. The most common clinical presentations include fever, shortness of breath, cough, myalgia, sore throat, vomiting, and headache. Critical cases were significantly higher in men (23% vs 8.7%), senior adults (>65 years), individuals of Bengali ethnicity, and in patients with comorbidities including diabetes, hypertension, and dyslipidemia (p =0.001). The case fatality rate was found to be 10%. The fatality was significantly higher in males than females (13.8% vs 2.6%), and in Asians (17.9%) than Arabs (6%) and Africans (0) (p =0.002). No association was found between viral load, represented by the RT-PCR cycle threshold (Ct) values, and severity of illness. CONCLUSION: Age, sex, and ethnicity are important predictors of COVID-19 severity. The cycle threshold (Ct) of the SARS-CoV-2 RT-PCR test cannot be used as a predictor of the criticality of illness.

High-Flow Nasal Cannula Treatment in Patients with COVID-19 Acute Hypoxemic Respiratory Failure: A Prospective Cohort Study.

BACKGROUND: Early use of high-flow nasal cannula (HFNC) decreases the need for endotracheal intubation (EI) in different respiratory failure causes. While HFNC is used in coronavirus disease 2019 (COVID-19)-related acute hypoxemic respiratory failure (AHRF) under weak recommendations, its efficacy remains to be investigated. OBJECTIVES: The primary objective was to examine HFNC efficacy in preventing EI among COVID-19 patients with AHRF. Secondary objectives were to determine predictors of HFNC success/failure, mortality rate, and length of hospital and intensive care unit (ICU) stay. PATIENTS AND METHODS: This is a prospective cohort study conducted at a single tertiary care centre in Saudi Arabia from April to August 2020. Adult patients admitted to the ICU with AHRF secondary to COVID-19 pneumonia and managed with HFNC were included. We excluded patients who were intubated or managed with non-invasive ventilation before HFNC. RESULTS: Forty-four patients received HFNC for a median duration of 3 days (interquartile range, 1-5 days). The mean age was 57 ± 14 years, and 86% were men. HFNC failure and EI occurred in 29 (66%) patients. Patients in whom HNFC treatment failed had a higher risk of death (52% versus 0%; P = 0.001). After adjusting for confounding factors, a high SOFA score and a low ROX index were significantly associated with HFNC failure (hazard ratio [HR], 1.42; 95% confidence interval [CI], 1.04-1.93; P = 0.025; and HR, 0.61; 95% CI, 0.42-0.88; P = 0.008, respectively). CONCLUSIONS: One-third of hypoxemic COVID-19 patients who received HFNC did not require intubation. High SOFA score and low ROX index were associated with HFNC failure.

Comorbidities and Risk Factors for Severe Outcomes in COVID-19 Patients in Saudi Arabia: A Retrospective Cohort Study.

PURPOSE: The first novel coronavirus disease-19 (COVID-19) case in the Kingdom of Saudi Arabia (KSA) was reported in Qatif in March 2020 with continual increase in infection and mortality rates since then. In this study, we aim to determine risk factors which effect severity and mortality rates in a cohort of hospitalized COVID-19 patients in KSA. METHOD: We reviewed medical records of hospitalized patients with confirmed COVID-19 positive results via reverse-transcriptase-polymerase-chain-reaction (RT-PCR) tests at Prince Mohammed Bin Abdulaziz Hospital, Riyadh between May and August 2020. Data were obtained for patient's demography, body mass index (BMI), and comorbidities. Additional data on patients that required intensive care unit (ICU) admission and clinical outcomes were recorded and analyzed with Python Pandas. RESULTS: A total of 565 COVID-19 positive patients were inducted in the study out of which, 63 (11.1%) patients died while 101 (17.9%) patients required ICU admission. Disease incidences were significantly higher in males and non-Saudi nationals. Patients with cardiovascular, respiratory, and renal diseases displayed significantly higher association with ICU admissions (p<0.001) while mortality rates were significantly higher in COVID-19 patients with cardiovascular, respiratory, renal and neurological diseases. Univariate cox proportional hazards regression model showed that COVID-19 positive patients requiring ICU admission [Hazard's ratio, HR=4.2 95% confidence interval, CI 2.5-7.2); p<0.001] with preexisting cardiovascular [HR=4.1 (CI 2.5-6.7); p<0.001] or respiratory [HR=4.0 (CI 2.0-8.1); p=0.010] diseases were at significantly higher risk for mortality among the positive patients. There were no significant differences in mortality rates or ICU admissions among males and females, and across different age groups, BMIs and nationalities. Hospitalized patients with cardiovascular comorbidity had the highest risk of death (HR=2.9, CI 1.7-5.0; p=0.020). CONCLUSION: Independent risk factors for critical outcomes among COVID-19 in KSA include cardiovascular, respiratory and renal comorbidities.

Applications of Big Data Analytics to Control COVID-19 Pandemic.

The COVID-19 epidemic has caused a large number of human losses and havoc in the economic, social, societal, and health systems around the world. Controlling such epidemic requires understanding its characteristics and behavior, which can be identified by collecting and analyzing the related big data. Big data analytics tools play a vital role in building knowledge required in making decisions and precautionary measures. However, due to the vast amount of data available on COVID-19 from various sources, there is a need to review the roles of big data analysis in controlling the spread of COVID-19, presenting the main challenges and directions of COVID-19 data analysis, as well as providing a framework on the related existing applications and studies to facilitate future research on COVID-19 analysis. Therefore, in this paper, we conduct a literature review to highlight the contributions of several studies in the domain of COVID-19-based big data analysis. The study presents as a taxonomy several applications used to manage and control the pandemic. Moreover, this study discusses several challenges encountered when analyzing COVID-19 data. The findings of this paper suggest valuable future directions to be considered for further research and applications.