Dexamethasone versus methylprednisolone for multiple organ dysfunction in COVID-19 critically ill patients: a multicenter propensity score matching study.

BACKGROUND: Dexamethasone usually recommended for patients with severe coronavirus disease 2019 (COVID-19) to reduce short-term mortality. However, it is uncertain if another corticosteroid, such as methylprednisolone, may be utilized to obtain better clinical outcome. This study assessed dexamethasone's clinical and safety outcomes compared to methylprednisolone. METHODS: A multicenter, retrospective cohort study was conducted between March 01, 2020, and July 31, 2021. It included adult COVID-19 patients who were initiated on either dexamethasone or methylprednisolone therapy within 24 h of intensive care unit (ICU) admission. The primary outcome was the progression of multiple organ dysfunction score (MODS) on day three of ICU admission. Propensity score (PS) matching was used (1:3 ratio) based on the patient's age and MODS within 24 h of ICU admission. RESULTS: After Propensity Score (PS) matching, 264 patients were included; 198 received dexamethasone, while 66 patients received methylprednisolone within 24 h of ICU admission. In regression analysis, patients who received methylprednisolone had a higher MODS on day three of ICU admission than those who received dexamethasone (beta coefficient: 0.17 (95% CI 0.02, 0.32), P = 0.03). Moreover, hospital-acquired infection was higher in the methylprednisolone group (OR 2.17, 95% CI 1.01, 4.66; p = 0.04). On the other hand, the 30-day and the in-hospital mortality were not statistically significant different between the two groups. CONCLUSION: Dexamethasone showed a lower MODS on day three of ICU admission compared to methylprednisolone, with no statistically significant difference in mortality.

Interferon Beta-1b and Lopinavir-Ritonavir for Middle East Respiratory Syndrome.

BACKGROUND: Whether combined treatment with recombinant interferon beta-1b and lopinavir-ritonavir reduces mortality among patients hospitalized with Middle East respiratory syndrome (MERS) is unclear. METHODS: We conducted a randomized, adaptive, double-blind, placebo-controlled trial that enrolled patients at nine sites in Saudi Arabia. Hospitalized adults with laboratory-confirmed MERS were randomly assigned to receive recombinant interferon beta-1b plus lopinavir-ritonavir (intervention) or placebo for 14 days. The primary outcome was 90-day all-cause mortality, with a one-sided P-value threshold of 0.025. Prespecified subgroup analyses and safety analyses were conducted. Because of the pandemic of coronavirus disease 2019, the data and safety monitoring board requested an unplanned interim analysis and subsequently recommended the termination of enrollment and the reporting of the results. RESULTS: A total of 95 patients were enrolled; 43 patients were assigned to the intervention group and 52 to the placebo group. A total of 12 patients (28%) in the intervention group and 23 (44%) in the placebo group died by day 90. The analysis of the primary outcome, with accounting for the adaptive design, yielded a risk difference of -19 percentage points (upper boundary of the 97.5% confidence interval [CI], -3; one-sided P = 0.024). In a prespecified subgroup analysis, treatment within 7 days after symptom onset led to lower 90-day mortality than use of placebo (relative risk, 0.19; 95% CI, 0.05 to 0.75), whereas later treatment did not. Serious adverse events occurred in 4 patients (9%) in the intervention group and in 10 (19%) in the placebo group. CONCLUSIONS: A combination of recombinant interferon beta-1b and lopinavir-ritonavir led to lower mortality than placebo among patients who had been hospitalized with laboratory-confirmed MERS. The effect was greatest when treatment was started within 7 days after symptom onset. (Funded by the King Abdullah International Medical Research Center; MIRACLE ClinicalTrials.gov number, NCT02845843.).

Revolutionizing healthcare: the role of artificial intelligence in clinical practice.

INTRODUCTION: Healthcare systems are complex and challenging for all stakeholders, but artificial intelligence (AI) has transformed various fields, including healthcare, with the potential to improve patient care and quality of life. Rapid AI advancements can revolutionize healthcare by integrating it into clinical practice. Reporting AI's role in clinical practice is crucial for successful implementation by equipping healthcare providers with essential knowledge and tools. RESEARCH SIGNIFICANCE: This review article provides a comprehensive and up-to-date overview of the current state of AI in clinical practice, including its potential applications in disease diagnosis, treatment recommendations, and patient engagement. It also discusses the associated challenges, covering ethical and legal considerations and the need for human expertise. By doing so, it enhances understanding of AI's significance in healthcare and supports healthcare organizations in effectively adopting AI technologies. MATERIALS AND METHODS: The current investigation analyzed the use of AI in the healthcare system with a comprehensive review of relevant indexed literature, such as PubMed/Medline, Scopus, and EMBASE, with no time constraints but limited to articles published in English. The focused question explores the impact of applying AI in healthcare settings and the potential outcomes of this application. RESULTS: Integrating AI into healthcare holds excellent potential for improving disease diagnosis, treatment selection, and clinical laboratory testing. AI tools can leverage large datasets and identify patterns to surpass human performance in several healthcare aspects. AI offers increased accuracy, reduced costs, and time savings while minimizing human errors. It can revolutionize personalized medicine, optimize medication dosages, enhance population health management, establish guidelines, provide virtual health assistants, support mental health care, improve patient education, and influence patient-physician trust. CONCLUSION: AI can be used to diagnose diseases, develop personalized treatment plans, and assist clinicians with decision-making. Rather than simply automating tasks, AI is about developing technologies that can enhance patient care across healthcare settings. However, challenges related to data privacy, bias, and the need for human expertise must be addressed for the responsible and effective implementation of AI in healthcare.

The effect of oseltamivir use in critically ill patients with COVID-19: A multicenter propensity score-matched study.

Background: Oseltamivir has been used as adjunctive therapy in the management of patients with COVID-19. However, the evidence about using oseltamivir in critically ill patients with severe COVID-19 remains scarce. This study aims to evaluate the effectiveness and safety of oseltamivir in critically ill patients with COVID-19. Methods: This multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care unit (ICU). Patients were categorized into two groups based on oseltamivir use within 48 hours of ICU admission (Oseltamivir vs. Control). The primary endpoint was viral load clearance. Results: A total of 226 patients were matched into two groups based on their propensity score. The time to COVID-19 viral load clearance was shorter in patients who received oseltamivir (11 vs. 16 days, p = 0.042; beta coefficient: -0.84, 95%CI: (-1.33, 0.34), p = 0.0009). Mechanical ventilation (MV) duration was also shorter in patients who received oseltamivir (6.5 vs. 8.5 days, p = 0.02; beta coefficient: -0.27, 95% CI: [-0.55,0.02], P = 0.06). In addition, patients who received oseltamivir had lower odds of hospital/ventilator-acquired pneumonia (OR:0.49, 95% CI:(0.283,0.861), p = 0.01). On the other hand, there were no significant differences between the groups in the 30-day and in-hospital mortality. Conclusion: Oseltamivir was associated with faster viral clearance and shorter MV duration without safety concerns in critically ill COVID-19 patients.

Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study.

BACKGROUND: Inhaled nitric oxide (iNO) is used as rescue therapy in patients with refractory hypoxemia due to severe COVID-19 acute respiratory distress syndrome (ARDS) despite the recommendation against the use of this treatment. To date, the effect of iNO on the clinical outcomes of critically ill COVID-19 patients with moderate-to-severe ARDS remains arguable. Therefore, this study aimed to evaluate the use of iNO in critically ill COVID-19 patients with moderate-to-severe ARDS. METHODS: This multicenter, retrospective cohort study included critically ill adult patients with confirmed COVID-19 treated from March 01, 2020, until July 31, 2021. Eligible patients with moderate-to-severe ARDS were subsequently categorized into two groups based on inhaled nitric oxide (iNO) use throughout their ICU stay. The primary endpoint was the improvement in oxygenation parameters 24 h after iNO use. Other outcomes were considered secondary. Propensity score matching (1:2) was used based on the predefined criteria. RESULTS: A total of 1598 patients were screened, and 815 were included based on the eligibility criteria. Among them, 210 patients were matched based on predefined criteria. Oxygenation parameters (PaO2, FiO2 requirement, P/F ratio, oxygenation index) were significantly improved 24 h after iNO administration within a median of six days of ICU admission. However, the risk of 30-day and in-hospital mortality were found to be similar between the two groups (HR: 1.18; 95% CI: 0.77, 1.82; p = 0.45 and HR: 1.40; 95% CI: 0.94, 2.11; p= 0.10, respectively). On the other hand, ventilator-free days (VFDs) were significantly fewer, and  ICU and hospital LOS were significantly longer in the iNO group. In addition, patients who received iNO had higher odds of acute kidney injury (AKI) (OR (95% CI): 2.35 (1.30, 4.26), p value = 0.005) and hospital/ventilator-acquired pneumonia (OR (95% CI): 3.2 (1.76, 5.83), p value = 0.001). CONCLUSION: In critically ill COVID-19 patients with moderate-to-severe ARDS, iNO rescue therapy is associated with improved oxygenation parameters but no mortality benefits. Moreover, iNO use is associated with higher odds of AKI, pneumonia, longer LOS, and fewer VFDs.

Evaluation of Low-Dose Aspirin use among Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study.

BACKGROUND: Aspirin is widely used as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. The literature has assessed and evaluated its role in hospitalized COVID-19 patients. However, no data are available regarding its role in COVID-19 critically ill patients. This study aimed to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in critically ill patients with COVID-19. METHOD: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to intensive care units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome was in-hospital mortality, and other outcomes were considered secondary. Propensity score matching was used (1:1 ratio) based on the selected criteria. RESULTS: A total of 1033 patients were eligible, and 352 patients were included after propensity score matching. The in-hospital mortality (HR 0.73 [0.56, 0.97], p = 0.03) was lower in patients who received aspirin during stay. Conversely, patients who received aspirin had a higher odds of major bleeding than those in the control group (OR 2.92 [0.91, 9.36], p = 0.07); however, this was not statistically significant. Additionally, subgroup analysis showed a possible mortality benefit for patients who used aspirin therapy prior to hospitalization and continued during ICU stay (HR 0.72 [0.52, 1.01], p = 0.05), but not with the new initiation of aspirin (HR 1.22 [0.68, 2.20], p = 0.50). CONCLUSION: Continuation of aspirin therapy during ICU stay in critically ill patients with COVID-19 who were receiving it prior to ICU admission may have a mortality benefit; nevertheless, it may be associated with an increased risk of significant bleeding. Appropriate evaluation for safety versus benefits of utilizing aspirin therapy during ICU stay in COVID19 critically ill patients is highly recommended.

The potential role of adjunctive ascorbic acid in the prevention of colistin-induced nephrotoxicity in critically ill patients: A retrospective study.

Background: Colistin is considered a valuable and last-resort therapeutic option for MDR gram-negative bacteria. Nephrotoxicity is the most clinically pertinent adverse effect of colistin. Vivo studies suggest that administering oxidative stress-reducing agents, such as ascorbic acid, is a promising strategy to overcome colistin-induced nephrotoxicity (CIN). However, limited clinical data explores the potential benefit of adjunctive ascorbic acid therapy for preventing CIN. Therefore, this study aims to assess the potential nephroprotective role of ascorbic acid as adjunctive therapy against CIN in critically ill patients. Method: This was a retrospective cohort study at King Abdulaziz Medical City (KAMC) for all critically ill adult patients who received IV colistin. Eligible patients were classified into two groups based on the ascorbic acid use as concomitant therapy within three days of colistin initiation. The primary outcome was CIN odds after colistin initiation, while the secondary outcomes were 30-day mortality, in-hospital mortality, ICU, and hospital LOS. Propensity score (PS) matching was used (1:1 ratio) based on the patient's age, SOFA score, and serum creatinine. Results: A total of 451 patients were screened for eligibility; 90 patients were included after propensity score matching based on the selected criteria. The odds of developing CIN after colistin initiation were similar between patients who received ascorbic acid (AA) as adjunctive therapy compared to patients who did not (OR (95 %CI): 0.83 (0.33, 2.10), p-value = 0.68). In addition, the 30-day mortality, in-hospital mortality, ICU, and hospital LOS were similar between the two groups. Conclusion: Adjunctive use of Ascorbic acid during colistin therapy was not associated with lower odds of CIN. Further studies with a larger sample size are required to confirm these findings.

The impact of early target attainment of vancomycin in critically ill patients with confirmed Gram-positive infection: A retrospective cohort study.

BACKGROUND: Vancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges, which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients.  This study aims to evaluate the timing to achieve therapeutic trough level of vancomycin on 30-day mortality in critically ill patients. METHOD: A retrospective cohort study was conducted for all adult critically ill patients with confirmed Gram-positive infection who received IV vancomycin between January 1, 2017, and December 31, 2020. We compared early (< 48 h) versus late (≥ 48 h) attainment of vancomycin therapeutic trough levels. The primary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were the development of resistant organisms, microorganisms eradication within 4-5 days of vancomycin initiation, acute kidney injury (AKI), and length of stay (LOS). Propensity score-matched (1:1 ratio) used based on patient's age, serum creatinine, and albumin values at baseline. RESULTS: A total of 326 patients were included; 110 patients attained the therapeutic trough levels within 48 h of vancomycin initiation. Late achievement of the therapeutic trough levels was associated with higher 30-day mortality (HR: 2.54; 95% CI [1.24-5.22]; p = 0.01). Additionally, patients who achieved therapeutic trough levels of vancomycin late were more likely to develop AKI (OR = 2.59; 95% CI [1.01-6.65]; p = 0.04). Other outcomes were not statistically significant between the two groups. CONCLUSION: Early achievement of vancomycin therapeutic levels in patients with confirmed Gram-positive infection was associated with possible survival benefits.

Association between tocilizumab and emerging multidrug-resistant organisms in critically ill patients with COVID-19: A multicenter, retrospective cohort study.

BACKGROUND: Tocilizumab is an IgG1 class recombinant humanized monoclonal antibody that directly inhibits the IL-6 receptor. Several randomized clinical trials have evaluated its safety and efficacy in patients with coronavirus disease 2019 (COVID-19), and these studies demonstrate conflicting results. Our study aimed to determine the association between tocilizumab treatment and microbial isolation and emergence of multidrug-resistant bacteria in critically ill patients with COVID-19. METHODS: A multicenter retrospective cohort study was conducted at two tertiary government hospitals in Saudi Arabia. All critically ill patients admitted to intensive care units with a positive COVID-19 PCR test between March 1 and December 31, 2020, who met study criteria were included. Patients who received tocilizumab were compared to those who did not receive it. RESULTS: A total of 738 patients who met our inclusion criteria were included in the analysis. Of these, 262 (35.5%) received tocilizumab, and 476 (64.5%) were included in the control group. Patients who received tocilizumab had higher odds for microbial isolation (OR 1.34; 95% CI 0.91-1.94, p = 0.13); however, the difference was not statistically significant. Development of resistant organisms (OR 1.00; 95% CI 0.51-1.98, p = 0.99) or detection of carbapenem-resistant Enterobacteriaceae (CRE) (OR 0.67; 95% CI 0.29-1.54, p = 0.34) was not statistically significant between the two groups. CONCLUSIONS: Tocilizumab use in critically ill patients with COVID-19 is not associated with higher microbial isolation, the emergence of resistant organisms, or the detection of CRE organisms.

Evaluation of zinc sulfate as an adjunctive therapy in COVID-19 critically ill patients: a two center propensity-score matched study.

BACKGROUND: Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. METHODS: Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. RESULTS: A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37-1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19-1.06; p = 0.07); however, it did not reach statistical significance. CONCLUSION: The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.

Evaluation of thiamine as adjunctive therapy in COVID-19 critically ill patients: a two-center propensity score matched study.

BACKGROUND: Thiamine is a precursor of the essential coenzyme thiamine pyrophosphate required for glucose metabolism; it improves the immune system function and has shown to reduce the risk of several diseases. The role of thiamine in critically ill septic patient has been addressed in multiple studies; however, it's role in COVID-19 patients is still unclear. The aim of this study was to evaluate the use of thiamine as an adjunctive therapy on mortality in COVID-19 critically ill patients. METHODS: This is a two-center, non-interventional, retrospective cohort study for critically ill patients admitted to intensive care units (ICUs) with a confirmed diagnosis of COVID19. All patients aged 18 years or older admitted to ICUs between March 1, 2020, and December 31, 2020, with positive PCR COVID-19 were eligible for inclusion. We investigated thiamine use as an adjunctive therapy on the clinical outcomes in critically ill COVID-19 patients after propensity score matching. RESULTS: A total of 738 critically ill patients with COVID-19 who had been admitted to ICUs were included in the study. Among 166 patients matched using the propensity score method, 83 had received thiamine as adjunctive therapy. There was significant association between thiamine use with in-hospital mortality (OR = 0.39; 95% CI 0.19-0.78; P value = 0.008) as well as the 30-day mortality (OR = 0.37; 95% CI 0.18-0.78; P value = 0.009). Moreover, patients who received thiamine as an adjunctive therapy were less likely to have thrombosis during ICU stay [OR (95% CI) 0.19 (0.04-0.88), P value = 0.03]. CONCLUSION: Thiamine use as adjunctive therapy may have potential survival benefits in critically ill patients with COVID-19. Additionally, it was associated with a lower incidence of thrombosis. Further interventional studies are required to confirm these findings.

Pregnant women's use and attitude toward herbal, vitamin, and mineral supplements in an academic tertiary care center, Riyadh, Saudi Arabia.

BACKGROUND: Herbal medicine has been widely utilized by pregnant women despite the limited available evidence regarding the safety and efficacy of that practice. The current available studies, from different countries, estimated that the use of herbal medicine during pregnancy range from 7% up to 96%. The aim of this study is to determine the prevalence, attitude, source of information, and reasoning behind the use of herbal medicine among pregnant women in Saudia Arabia. METHODS: A cross-sectional study conducted using a convenience sample including pregnant women who visited the obstetric clinics at King Abdulaziz Medical City in Riyadh, Saudi Arabia. A survey was administered in order to evaluate the prevalence and perception toward herbal medicine use among pregnant women in Saudi Arabia. RESULTS: A total of 297 pregnant women completed the survey. The results showed that 56% of the respondents have used some type of herbal medicine during their pregnancy. Olive oil was utilized in 26% of the respondents followed by cumin 20% and garlic 15%. In addition, 37% of the respondents used herbal medicine by their own initiative, while 33% and 12% used herbal medicine based on recommendations from their families and friends, respectively. Furthermore, 19% of the respondents reported a positive attitude toward herbal medicine use during pregnancy. In addition, the percentage of women with positive attitude was marginally higher among respondents with lower educational level. CONCLUSION: The prevalence of using herbal medicine is considerably high among pregnant women in Saudi Arabia. Unfortunately, the majority of the users relied on informal sources to use herbal medicine during pregnancy.

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.

OBJECTIVE: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. STUDY SELECTION: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. DATA SOURCES: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. DATA EXTRACTION: Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. DATA SYNTHESIS: Use of aspirin was associated with a 7% (95% CI, 2-12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I = 61.6%). CONCLUSIONS: These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

Comparison of the safety and efficacy for different regimens of pharmaco-prophylaxis among severely burned patients: a randomized controlled trial.

PURPOSE: Venous thromboembolism (VTE) is a common complication in critically ill patients, including severe burn cases. Burn patients respond differently to medications due to pharmacokinetic changes. This study aims to assess the feasibility and safety of different VTE pharmaco-prophylaxis in patients admitted to the ICU with severe burns. METHODS: A pilot, open-label randomized controlled trial was conducted on ICU patients with severe burns (BSA ≥ 20%). By using block randomization, patients were allocated to receive high-dose enoxaparin 30 mg q12hours (E30q12), standard-dose enoxaparin 40 mg q24hours (E40q24), or unfractionated heparin (UFH) 5000 Units q8hours. In this study, the primary outcomes assessed were the recruitment and consent rates, as well as bleeding or hematoma at both the donor and graft site. Additionally, secondary measures were evaluated to provide further insights. RESULTS: Twenty adult patients out of 114 screened were enrolled and received E30q12 (40%), E40q24 (30%), and UFH (30%). The recruitment rate was one patient per month with a 100% consent rate. Donor site bleeding occurred in one patient (16.7%) in the UFH group. On the other hand, graft site bleeding was only reported in one patient (12.5%) who received E30q12. Major bleeding happened in two patients, one in E30q12 and one in the UFH group. Five patients (25.0%) had minor bleeding; two patients (25.0%) received E30q12, two patients E40q24, and one patient UFH. RBC transfusion was needed in four patients, two on E30q12 and two on UFH. Only one patient had VTE, while four patients died in the hospital. CONCLUSION: The study observed a low recruitment rate but a high consent rate. Furthermore, there were no major safety concerns identified with any of the three pharmacologic prophylaxis regimens that were evaluated. TRIAL REGISTRATION NUMBER: NCT05237726.

Clonidine safety and effectiveness in the management of suspected paroxysmal sympathetic hyperactivity post-traumatic brain injury: A retrospective cohort study.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. In addition, TBI may cause paroxysmal sympathetic hyperactivity (PSH), which is associated with poor clinical outcomes. This study aimed to evaluate the safety and effectiveness of clonidine in patients with TBI and suspected PSH. METHODS: A retrospective cohort study for critically ill patients with TBI with suspected PSH admitted to intensive care units (ICUs) from 1 May 2016 to 31 January 2020 at a tertiary academic medical center. Eligible patients were categorized based on clonidine use during their ICU stay (Clonidine group vs. Control group). The primary outcome was the improvement in functional outcomes during ICU stay, defined by a delta Glasgow Coma Score (GCS). Secondary outcomes included ICU and hospital length of stay, heart rate variation, and 90-day mortality. RESULTS: A total of 2915 patients were screened, of which 169 were included. Based on multiple regression analysis, patients who received clonidine showed better improvement in functional outcomes by a higher mean delta GCS than patients who did not (Beta Coeff. 0.41; CI: 0.07 - 0.74; P = 0.02). In addition, the patient's GCS upon ICU discharge and IV opioids requirement on day three were higher in the clonidine group than control (beta coefficient (95% CI): 0.18 (0.03, 0.32); p = 0.02 and beta coefficient (95% CI): 1.38 (0.24, 2.52); p = 0.02, respectively). No statistical differences were observed in any of the other secondary outcomes after adjusting for confounders. CONCLUSION: This study found that patients who received clonidine had better functional outcomes during their ICU stay, as shown by their delta GCS than those who did not. Other outcomes were similar between the groups. More data are needed to explore the role of clonidine in patients with TBI with suspected PSH.

Practical Guide for Anticoagulant and Antiplatelet Reversal in Clinical Practice.

In recent years, anticoagulant and antiplatelet use have increased over the past years for the prevention and treatment of several cardiovascular conditions. Due to the rising use of antithrombotic medications and the complexity of specific clinical cases requiring such therapies, bleeding remains the primary concern among patients using antithrombotics. Direct oral anticoagulants (DOACs) include rivaroxaban, apixaban, edoxaban, and betrixaban. Direct thrombin inhibitors (DTIs) include argatroban, bivalirudin, and dabigatran. DOACs are associated with lower rates of fatal, life-threatening, and significant bleeding risks compared to those of warfarin. The immediate reversal of these agents can be indicated in an emergency setting. Antithrombotic reversal recommendations are still in development. Vitamin K and prothrombin complex concentrate (PCCs) can be used for warfarin reversal. Andexanet alfa and idarucizumab are specific reversal agents for DOACs and DTIs, respectively. Protamine sulfate is the solely approved reversal agent for unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). However, there are no specific reversal agents for antiplatelets. This article aims to provide a practical guide for clinicians regarding the reversal of anticoagulants and antiplatelets in clinical practice based on the most recent studies.

Type I interferon autoantibodies in hospitalized patients with Middle East respiratory syndrome and association with outcomes and treatment effect of interferon beta-1b in MIRACLE clinical trial.

Background: Type I interferons (IFNs) are essential antiviral cytokines induced upon respiratory exposure to coronaviruses. Defects in type I IFN signaling can result in severe disease upon exposure to respiratory viral infection and are associated with worse clinical outcomes. Neutralizing autoantibodies (auto-Abs) to type I IFNs were reported as a risk factor for life-threatening COVID-19, but their presence has not been evaluated in patients with severe Middle East respiratory syndrome (MERS). Methods: We evaluated the prevalence of type I IFN auto-Abs in a cohort of hospitalized patients with MERS who were enrolled in a placebo-controlled clinical trial for treatment with IFN-ß1b and lopinavir-ritonavir (MIRACLE trial). Samples were tested for type I IFN auto-Abs using a multiplex particle-based assay. Results: Among the 62 enrolled patients, 15 (24.2%) were positive for immunoglobulin G auto-Abs for at least one subtype of type I IFNs. Auto-Abs positive patients were not different from auto-Abs negative patients in age, sex, or comorbidities. However, the majority (93.3%) of patients who were auto-Abs positive were critically ill and admitted to the ICU at the time of enrollment compared to 66% in the auto-Abs negative patients. The effect of treatment with IFN-ß1b and lopinavir-ritonavir did not significantly differ between the two groups. Conclusion: This study demonstrates the presence of type I IFN auto-Abs in hospitalized patients with MERS.

Therapeutic Plasma Exchange and Supratherapeutic Levels of Unfractionated Heparin in the Management of Critically Ill Patient with Myasthenia Gravis: A Case Report.

BACKGROUND Therapeutic plasma exchange (TPE) is an extracorporeal method of filtration indicated in several conditions, including myasthenia gravis (MG). The removal and replacement of plasma through TPE affect the level of coagulation factors, suggesting alterations in homeostasis. TPE also has the potential to remove medications from the plasma. Insufficient data are available that evaluate the effect of TPE on certain medications, such as unfractionated heparin (UFH). CASE REPORT We report a case of a 78-year-old woman with MG. She underwent a thymectomy complicated by phrenic nerve injury and respiratory failure, requiring admission to the Intensive Care Unit (ICU) and mechanical ventilation. She developed a provoked left upper extremity deep venous thrombosis and started on therapeutic UFH with a target activated partial thromboplastin time (aPTT) of 50 to 80 seconds. Despite being on immunosuppressants, additional therapy with TPE was deemed necessary for her MG exacerbation. Therefore, she received 5 sessions of TPE, given every other day. Interestingly, while on TPE therapy, the aPTT increased significantly after each administration, with TPE reaching >170 seconds in some instances. As a precautionary measure, heparin infusion was held for 1 day based on the institutional heparin protocol and the physician's decision. Fortunately, the patient did not develop any bleeding complications. CONCLUSIONS TPE treatment may temporarily deplete the coagulation factors, leading to supratherapeutic aPTT levels. UFH dose adjustment and frequent assessment of aPTT levels are essential during TPE treatment to minimize serious bleeding complications. Future studies with a larger sample size are required to focus on understanding the effect of TPE on medications.

Colistin Loading Dose in Septic Patients with Gram Negative Infections.

Purpose: Intravenous (IV) colistin is commonly used to treat multidrug-resistant gram-negative infections. It is primarily eliminated renally and may induce acute kidney injury (AKI) at a rate of up to 53%. Consequently, septic patients who require colistin administration have an additional risk of developing AKI. The aim of this study is to investigate clinical failure and AKI predictors for septic patients treated with IV colistin. Methods: This retrospective cohort study was conducted at a tertiary teaching hospital in Saudi Arabia. Adult septic patients with suspected or confirmed gram-negative infections who received colistin admitted to the hospital between May 2016 and December 2020 were screened after obtaining IRB approval. AKI was defined based on the AKI Network criteria. We investigated the incidence of clinical failure based on colistin dosing and AKI risk factors, such as the development of septic shock, severity of illness, and medication co-administration using a multiple logistic regression model. Results: After screening 163 patients, 103 patients were included in the analysis. No difference was observed between the colistin dosing strategies for clinical failure. Of the included predictors, development of septic shock (OR: 3.75; 95% CI 1.18-13.15), carbapenem co-administration (OR, 3.96; 95% CI, 1.134-15.57) were associated with an increased risk of AKI. The other factors were not significant predictors. Conclusion: Clinical failure was not affected by colistin dosing strategies in our cohort of patients with sepsis. Moreover, the co-administration of carbapenems and the development of septic shock may increase the risk of inducing AKI in adult septic patients treated with IV colistin. Further studies are required to confirm these findings.

Statins and Risk of Thrombosis in Critically ill Patients with COVID-19: A Multicenter Cohort Study.

PURPOSE: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. METHODS: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. RESULTS: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. CONCLUSION: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.