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.

Pituitary Apoplexy After a Major Abdominal Surgery: A Case Report.

Pituitary apoplexy is a major complication of pituitary adenoma, and the diagnosis might be challenging if the patient presents with signs of meningeal irritation or electrolyte imbalance. It can be fatal if not diagnosed and treated appropriately. Apoplexy is the first clinical presentation in the majority of pituitary adenoma cases. The pathophysiology of pituitary apoplexy involves bleeding and/or ischemia of pituitary enlargement. In this case report, we present a case of pituitary apoplexy that developed after a major abdominal surgery. The patient presented with headache, hypertension, and visual loss. After confirming the diagnosis through a CT scan, the patient underwent a transsphenoidal surgical decompression.

Application of temperature-dependent and steered molecular dynamics simulation to screen anti-dengue compounds against Marburg virus.

Marburg virus infections are extremely fatal with a fatality range of 23% to 90%, therefore there is an urgent requirement to design and develop efficient therapeutic molecules. Here, a comprehensive temperature-dependent molecular dynamics (MD) simulation method was implemented to identify the potential molecule from the anti-dengue compound library that can inhibit the function of the VP24 protein of Marburg. Virtual high throughput screening identified five effective binders of VP24 after screening 484 anti-dengue compounds. These compounds were treated in MD simulation at four different temperatures: 300, 340, 380, and 420 K. Higher temperatures showed dissociation of hit compounds from the protein. Further, triplicates of 100 ns MD simulation were conducted which showed that compounds ID = 118717693, and ID = 5361 showed strong stability with the protein molecule. These compounds were further validated using ΔG binding free energies and they showed: -30.38 kcal/mol, and -67.83 kcal/mol binding free energies, respectively. Later, these two compounds were used in steered MD simulation to detect its dissociation. Compound ID = 5361 showed the maximum pulling force of 199.02 kcal/mol/nm to dissociate the protein-ligand complex while ID = 118717693 had a pulling force of 101.11 kcal/mol/nm, respectively. This ligand highest number of hydrogen bonds with varying occupancies at 89.93%, 69.80%, 57.93%, 52.33%, and 50.63%. This study showed that ID = 5361 can bind with the VP24 strongly and has the potential to inhibit its function which can be validated in the in-vitro experiment.Communicated by Ramaswamy H. Sarma.

Prognostic accuracy of qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients presenting with suspected infection to the emergency department (PASSEM) Multicenter prospective external validation cohort study protocol.

BACKGROUND: Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. METHODS AND ANALYSIS: PASSEM study is an international prospective external validation cohort study. For 9 months, each participating center will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalization. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., ≥72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enroll 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. DISCUSSION: PASSEM study will be the first international multicenter prospective cohort study that designated to externally validate qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients with suspected infection presenting to the ED in the Middle East region. STUDY REGISTRATION: The study is registered at ClinicalTrials.gov (NCT05172479).

Awareness of chronic obstructive pulmonary disease (COPD) among the general population in Aseer Region, Kingdom of Saudi Arabia (KSA).

Background: Chronic obstructive pulmonary disease (COPD) is a common but preventable disease and has a prevalence of 5%-14% in the general population. It is characterized by airflow limitation and persistent respiratory symptoms. In this survey, we aimed to assess the awareness of COPD among the general population in the Aseer Region of the Kingdom of Saudi Arabia (KSA). Method: This was an observational, cross-sectional study in which predesigned electronic questionnaires were distributed to 504 randomly selected community personnel utilizing phone services. The collected data were analyzed using the IBM SPSS Statistics software, version 24 for Windows (IBM Corp., Armonk, NY). Results: Participants were asked 11 questions with yes-or-no answers based on awareness and symptoms of COPD: 35.5% of participants had heard about the COPD as a term and 72% had no detailed information about COPD. Only 3.5% of participants had relatives with COPD. During the survey on COPD symptoms, 31% of participants chose shortness of breath and the rest chose cough (20%), sputum production (15%), wheezing (14%), and chest pain (19%). Almost two-third of the participants had no idea about COPD symptoms. For the most disease knowledge, majority of the study participants had very poor knowledge about the disease that was evident in the 22 questions intended to assess this domain. Social media sites ranked as the most popular source of information on COPD among the study participants. Conclusion: Awareness about COPD among the general population in the Aseer Region in KSA is poor. It is advisable to carry out programs to increase their level of awareness.

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.

The microbiological profile of isolates recovered from ICU patients with traumatic brain injuries at a tertiary care center, Southern Region, Saudi Arabia.

INTRODUCTION: Traumatic head injury THI is a Neurosurgical condition in which brain function is interrupted as a result of blunt (motor vehicle accidents MVA, falls, and assaults) or penetrating trauma. Nearly half of all injuries are caused by head trauma. Head traumas are a leading cause of death and organ loss in young people, where this population accounts for the vast majority of TBI patients. METHODOLOGY: This retrospective cohort study was conducted at Asir Central Hospital, KSA with data from 2015 to 2019. Records of bacterial cultures and outcomes such as length of stay in the hospital were analyzed. In addition, treatment outcomes were also analyzed. RESULTS: A total of 300 ICU patient samples (69 patients) were included. Patients' ages ranged from 13 to 87 years with a mean age of 32.4 ± 17.5 years old. The most frequently reported diagnosis was RTA (71 %), followed by SDH (11.6 %), The most isolated organisms from the recovered samples were Klebsiella pneumoniae (27 %), followed by Pseudomonas aeruginosa (14.7 %). Regarding susceptibility, Tigecycline was the most sensitive (44 %), followed by Gentamicin (43.3 %). A total of 36 (52.2 %) patients stayed for less than one month, 24 (34.8 %) stayed for 1-3 months, and 7 (10.1 %) stayed for 3-6 months. The mortality rate in our study population was (40.6 %) as 28 patients died. CONCLUSION: The prevalence of pathogens in TBI needs to be determined in different institutions for the establishment of effective empiric antibiotic treatment following infections in traumatic brain injuries. This will ultimately help to improve treatment outcomes. In neurosurgical patients undergoing cranial procedures after trauma, a hospital-standardized antibiotic policy is effective in achieving low rates of bacterial infections especially MDR infections.

An Overview of Clinical Manifestations of Dermatological Disorders in Intensive Care Units: What Should Intensivists Be Aware of?

Acute skin failure is rarely the primary diagnosis that necessitates admission to an intensive care unit. Dermatological manifestations in critically ill patients, on the other hand, are relatively common and can be used to make a key diagnosis of an adverse drug reaction or an underlying systemic illness, or they may be caused by factors related to a prolonged stay or invasive procedures. In intensive care units, their classification is based on the aetiopathogenesis of the cutaneous lesion and, in the meantime, distinguishes critical patients. When evaluating dermatological manifestations, several factors must be considered: onset, morphology, distribution, and associated symptoms and signs. This review depicts dermatological signs in critical patients in order to lay out better recognition.

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).

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.

The Relationship of ABO and Rh Blood Group Types With Severe COVID-19 Disease Mortality in ICU Patients: Insights From a Single-Center Experience in Southern Saudi Arabia.

Introduction The global COVID-19 pandemic has triggered an unprecedented public health crisis, emphasizing the need to understand factors influencing disease outcomes. This study explores the role of genetic variations in blood group antigens, particularly ABO and RhD, in shaping mortality rates among critically ill COVID-19 patients in the southern region of Saudi Arabia. Methods Utilizing a retrospective, noninterventional approach, we analyzed medical records of 594 COVID-19 patients admitted to the intensive care unit (ICU) at Aseer Central Hospital from August 2020 to April 2021. The cohort, with a mean age of 60.5 years, consisted of a predominantly male population. Results The study encompassed a diverse age range of 18 to 103 years, with a mean age of 60.5 ± 17.3 years. Of the 594 patients, 398 (67%) were male, and only 5 (0.8%) had a history of smoking. Blood group distribution revealed 275 (48.4%) with O-, 189 (33.3%) with A+, and 51 (9%) with AB- types. Predominant chronic conditions included diabetes mellitus (35.5%). Tragically, 320 patients (54.6%) experienced mortality, with a 100% mortality rate for the B+ blood group and 92.9% for O- blood group. Conclusion This analysis establishes significant statistical links, underscoring the pivotal role of blood type, particularly the Rh factor, in influencing mortality risk among critically ill COVID-19 patients. These findings contribute valuable insights into risk stratification and personalized care for severe cases, emphasizing the importance of genetic considerations in understanding disease outcomes.

An unusual presentation of acute diaphragmatic hernia complicated by tension gastrothorax an under-recognized cause of cardiac arrest due to a fall from a height: A case report and literature review.

A diaphragmatic hernia is a protrusion of the abdominal contents into the negative pressure thoracic cavity through a congenital or acquired diaphragmatic defect. Generally, acquired diaphragmatic hernia is a rare, life-threatening condition that usually follows blunt/penetrating trauma or an iatrogenic cause, resulting in the diaphragmatic rupture, accompanied by the herniation of abdominal visceral organs. We report a 47-year-old male construction worker who sustained a fall from a height of about 30 feet height. He presented with hypoxia initially and, after a primary survey, was found to have a traumatic rupture of the diaphragm with herniation of the stomach and abdominal contents, causing signs of obstructive shock. After adequate resuscitation in the Emergency Department, he was rushed to operating room. There, he suffered two very short pulseless electrical activity cardiac arrests. Therefore, an emergency anterolateral thoracotomy was done, and it was extended into laparotomy to reduce the abdominal contents through the diaphragmatic tear of 12 cm, which restored the spontaneous circulation. He recovered eventually, despite chest infections and pulmonary atelectasis, and was discharged on the 28th day and remained in good condition during the outpatient visit. Tension gastrothorax or viscerothorax is rare, but an under-recognized cause of cardiac arrest in the trauma setting necessitates a vigilant evaluation and early suspicion to prevent a catastrophic outcome. This case report emphasizes the inclusion of tension viscero or abdominal thorax as one of the recognizable causes of a pulseless electrical activity cardiac arrest.

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.

Neurogenic Appendicitis: A Reappraisal of the Clinicopathological Features and Pathogenesis.

In 1921; Masson and Maresch first coined the term "neurogenic appendicitis (NA)" to describe "neuroma-like" lesions in the appendix. To date, our knowledge about NA is limited; therefore, we conducted a comprehensive analysis of the literature (1921 to 2020) to examine the clinicopathological features of NA. We also addressed the pathophysiology of acute abdominal pain and fibrosis in this entity. We performed a meta-analysis study by searching the PubMed database, using several keywords, such as: "appendix," "neurogenic," "obliterative," "neuroma," "fibrous obliteration," "appendicopathy," and "appendicitis." Our study revealed that patients with NA usually present clinically with features of acute appendicitis, bud2t they have grossly unremarkable appendices. Histologically, the central appendiceal neuroma was the most common histological variant of NA, followed by the submucosal and intramucosal variants. To conclude, NA represents a form of neuroinflammation. The possibility of NA should be considered in patients with clinical features of acute appendicitis who intraoperatively show a grossly unremarkable appendix. Neuroinflammation and neuropeptides play roles in the development of pain and fibrosis in NA.

Differential impact of the angiotensin-converting enzyme-2 (ACE2 rs4343 G>A) and miR-196a2 rs11614913 C>T gene alterations in COVID-19 disease severity and mortality.

The recent coronavirus outbreak from Wuhan China in late 2019 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in a global pandemic of coronavirus-19 disease (COVID-19). Understating the underlying mechanism of the pathogenesis of coronavirus infection is important not only because it will help in accurate diagnosis and treatment of the infection but also in the production of effective vaccines. The infection begins when SARS-CoV-2 enters the cells through binding of its envelope glycoprotein to angiotensin-converting enzyme2 (ACE2). Gene variations of ACE2 and microRNA (miR)-196 are associated with viral infection and other diseases. The present study investigated the association of the ACE2 rs4343 G>A and miR-196a2 rs11614913 C>T gene polymorphisms with severity and mortality of COVID-19 using amplification refractory mutation system PCR in 117 COVID-19 patients and 103 healthy controls from three regions of Saudi Arabia. The results showed that ACE2 rs4343 GA genotype was associated with severity of COVID-19 (OR=2.10, P-value 0.0028) and ACE2 rs4343 GA was associated with increased mortality with OR=3.44, P-value 0.0028. A strong correlation between the ACE2 rs4343 G>A genotype distribution among COVID-19 patients was reported with respect to their comorbid conditions including sex (P<0.023), coronary artery disease (P<0.0001), oxygen saturation <60 mm Hg (P<0.0009) and antiviral therapy (0.003). The results also showed that the CT genotype and T allele of the miR-196a2 rs11614913 C>T were associated with decreased risk to COVID-19 with OR=0.76, P=0.006 and OR=0.54, P=0.005, respectively. These results need to be validated with future molecular genetic studies in a larger sample size and different populations.

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).

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.

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section.

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

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.

COVID-19 Psychological Impact on Health Care Workers in Saudi Arabia.

OBJECTIVE: Little is known about the impact of Coronavirus (COVID-19) among the health care workers in Saudi Arabia. Therefore, the present study aimed to assess the psychological impact of COVID-19 among the health care workers. METHODS: A cross-sectional survey was conducted from May till mid-July among 389 health care workers from government and private hospitals in Saudi Arabia. Data was collected using a pre-structured online questionnaire that measured adverse psychological outcomes, including the Patient Health Questionnaire-9 (PHQ-9) scale and the Generalized Anxiety Disorder 7-item (GAD-7) scale. The Pearson chi-square test was used to assess the distribution of depression and anxiety among health care workers. RESULTS: A high level of anxiety was recorded among the health care workers, and 69.3% of health care workers below the age of 40 were found to have depression. There was a significant increase in depression among staff with chronic health problems (72.1% vs. 61.9%; p = 0.048). High anxiety levels were detected among young staff compared to others (68.7% vs. 43.8%; p = 0.001). Moreover, 82.1% of the female staff were anxious, as compared to 55.6% of the males (p = 0.001). CONCLUSIONS: We found increased prevalence of adverse psychological outcomes among the health care workers in Saudi Arabia during the outbreak of COVID-19. Therefore, there is a need for proper screening and development of corresponding preventive measures to decrease the adverse psychological outcomes.