The utility of serum glucose potassium ratio as a predictive factor for haemorrhagic transformation, stroke recurrence, and mortality among ischemic stroke patients.

Background and Objective: Glucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes in stroke patients has not been investigated. Our study evaluated the applicability of baseline GPR as a predictive prognostic tool for clinical outcomes in ischemic stroke patients. Methods: The multicenter retrospective cohort study included acute-subacute adult ischemic stroke patients who had their baseline serum GPR levels measured. Eligible patients were categorized into two sub-cohorts based on the baseline GPR levels (<1.67 vs. ≥ 1.67). The primary outcome was the incidence of 30-day hemorrhagic transformation, while stroke recurrence, and all-cause mortality within twelve months, were considered secondary. Results: Among 4083 patients screened, 1047 were included in the current study. In comparison with GPR < 1.67 group, patients with ≥ 1.67 GPR had a significantly higher ratio of all-cause mortality within twelve months (aHR 2.07 [95 % CI 1.21-3.75] p = 0.01), and higher ratio of 30-day hemorrhagic transformation but failed to reach the statistical significance (aHR 1.60 [95 % CI 0.95-2.79], p = 0.08). Conclusion: Overall, baseline GPR serum is an independent predictor of all-cause mortality within twelve months in patients with acute and subacute ischemic stroke. Further clinical studies are necessary to validate these findings.

The concomitant use of ultra short beta-blockers with vasopressors and inotropes in critically ill patients with septic shock: A systematic review and meta-analysis of randomized controlled trials.

Background: Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that requires vasopressor or inotropic support. The regulation of immune function in sepsis is complex and varies over time. However, activating Beta-2 receptors and blocking Beta-1 receptors reduces the proinflammatory response by influencing cytokine production. Evidence that supports the concomitant use of ultra short beta-blockers with inotropes and vasopressors in patients with septic shock is still limited. This study aimed to evaluate the use of ultra short beta-blockers and its impact on the ICU related outcomes such as mortality, length of stay, heart rate control, shock resolution, and vasopressors/inotropes requirements. Methods: A systematic review and meta-analysis of randomized controlled trials including critically ill patients with septic shock who received inotropes and vasopressors. Patients who received either epinephrine or norepinephrine without beta-blockers "control group" were compared to patients who received ultra short beta-blockers concomitantly with either epinephrine or norepinephrine "Intervention group". MEDLINE and Embase databases were utilized to systematically search for studies investigating the use of ultra short beta-blockers in critically ill patients on either epinephrine or norepinephrine from inception to October 10, 2023. The primary outcome was the 28-day mortality. While, length of stay, heart rate control, and inotropes/ vasopressors requirements were considered secondary outcomes. Results: Among 47 potentially relevant studies, nine were included in the analysis. The 28-day mortality risk was lower in patients with septic shock who used ultra short beta-blockers concomitantly with either epinephrine or norepinephrine compared with the control group (RR (95%CI): 0.69 (0.53, 0.89), I2=26%; P=0.24). In addition, heart rate was statistically significantly lower with a standardized mean difference (SMD) of -22.39 (95% CI: -24.71, -20.06) among the beta-blockers group than the control group. The SMD for hospital length of stay and the inotropes requirement were not statistically different between the two groups (SMD (95%CI): -0.57 (-2.77, 1.64), and SMD (95%CI): 0.08 (-0.02, 0.19), respectively). Conclusion: The use of ultra short beta-blockers concomitantly with either epinephrine or norepinephrine in critically ill patients with septic shock was associated with better heart rate control and survival benefits without increment in the inotropes and vasopressors requirement.

Assessing glycemic variability in critically ill patients: A prospective cohort study comparing insulin infusion therapy with insulin sliding scale.

Glycemic variability (GV) has been associated with an increased mortality rate among critically ill patients. The clinical outcomes of having less GV even with slight hyperglycemia are better than those having tight glycemic control but higher GV. Insulin infusion remains the preferred method to control stress hyperglycemia in critically ill patients. However, its impacts on GV and clinical outcomes in critically ill patients still need further investigation. This study intended to evaluate the impact of insulin infusion therapy (IIT) compared to the insulin sliding scale (ISS) on the extent of GV and explore its impact on the clinical outcomes for critically ill patients. A prospective, single-center observational cohort study was conducted at a tertiary academic hospital in Saudi Arabia between March 2021 and November 2021. The study included adult patients admitted to ICUs who received insulin for stress hyperglycemia management. Patients were categorized into two groups based on the regimen of insulin therapy during ICU stay (IIT versus ISS). The primary outcome was the GV between the two groups. Secondary outcomes were ICU mortality, the incidence of hypoglycemia, and ICU length of stay (LOS). A total of 381 patients were screened; out of them, eighty patients met the eligibility criteria. The distribution of patients having diabetes and a history of insulin use was similar between the two groups. The GV was lower in the IIT group compared to the ISS group using CONGA (- 0.65, 95% CI [- 1.16, - 0.14], p-value = 0.01). Compared with ISS, patients who received IIT had a lower incidence of hypoglycemia that required correction (6.8% vs 2.77%; p-value = 0.38). In contrast, there were no significant differences in ICU LOS and ICU mortality between the two groups. Our study demonstrated that the IIT is associated with decreased GV significantly in critically ill patients without increasing the incidence of severe hypoglycemia. There is no survival benefit with the use of the IIT. Further studies with larger sample size are required to confirm our findings and elaborate on IIT's potential effect in reducing ICU complications in critically ill patients.

Ketamine-based Sedation Use in Mechanically Ventilated Critically Ill Patients with COVID-19: A Multicenter Cohort Study.

Backgrounds: Ketamine possesses analgesia, anti-inflammation, anticonvulsant, and neuroprotection properties. However, the evidence that supports its use in mechanically ventilated critically ill patients with COVID-19 is insufficient. The study's goal was to assess ketamine's effectiveness and safety in critically ill, mechanically ventilated (MV) patients with COVID-19. Methods: Adult critically ill patients with COVID-19 were included in a multicenter retrospective-prospective cohort study. Patients admitted between March 1, 2020, and July 31, 2021, to five ICUs in Saudi Arabia were included. Eligible patients who required MV within 24 hours of ICU admission were divided into two sub-cohort groups based on their use of ketamine (Control vs. Ketamine). The primary outcome was the length of stay (LOS) in the hospital. P/F ratio differences, lactic acid normalization, MV duration, and mortality were considered secondary outcomes. Propensity score (PS) matching was used (1:2 ratio) based on the selected criteria. Results: In total, 1,130 patients met the eligibility criteria. Among these, 1036 patients (91.7 %) were in the control group, whereas 94 patients (8.3 %) received ketamine. The total number of patients after PS matching, was 264 patients, including 88 patients (33.3 %) who received ketamine. The ketamine group's LOS was significantly lower (beta coefficient (95 % CI): -0.26 (-0.45, -0.07), P = 0.008). Furthermore, the PaO2/FiO2 ratio significantly improved 24 hours after the start of ketamine treatment compared to the pre-treatment period (6 hours) (124.9 (92.1, 184.5) vs. 106 (73.1, 129.3; P = 0.002). Additionally, the ketamine group had a substantially shorter mean time for lactic acid normalization (beta coefficient (95 % CI): -1.55 (-2.42, -0.69), P 0.01). However, there were no significant differences in the duration of MV or mortality. Conclusions: Ketamine-based sedation was associated with lower hospital LOS and faster lactic acid normalization but no mortality benefits in critically ill patients with COVID-19. Thus, larger prospective studies are recommended to assess the safety and effectiveness of ketamine as a sedative in critically ill adult patients.

The Predictors and Risk Factors of 2-Year Rejection in Renal Transplant Patients: A Multicenter Case-Control Study.

INTRODUCTION: Kidney transplantation is a definitive treatment for end-stage renal disease. It is associated with improved life expectancy and quality of life. One of the most common complications following kidney transplantation is graft rejection. To our knowledge, no previous study has identified rejection risk factors in kidney transplant recipients in Saudi Arabia. Therefore, this study aimed to determine the specific risk factors of graft rejection. METHODS: A multicenter case-control study was conducted at four transplant centers in Saudi Arabia. All adult patients who underwent a renal transplant between January 1, 2015 and December 31, 2021 were screened for eligibility. Included patients were categorized into two groups (cases and control) based on the occurrence of biopsy-proven rejection within 2 years. The primary outcome was to determine the risk factors for rejection within the 2 years of transplant. Exact matching was utilized using a 1:4 ratio based on patients' age, gender, and transplant year. RESULTS: Out of 1,320 screened renal transplant recipients, 816 patients were included. The overall prevalence of 2-year rejection was 13.9%. In bivariate analysis, deceased donor status, the presence of donor-specific antibody (DSA), intraoperative hypotension, Pseudomonas aeruginosa, Candida, and any infection within 2 years were linked with an increased risk of 2-year rejection. However, in the logistic regression analysis, the presence of DSA was identified as a significant risk for 2-year rejection (adjusted OR: 2.68; 95% CI: 1.10, 6.49, p = 0.03). Furthermore, blood infection, infected with Pseudomonas aeruginosa or BK virus within 2 years of transplant, were associated with higher odds of 2-year rejection (adjusted OR: 3.10; 95% CI: 1.48, 6.48, p = 0.003, adjusted OR: 3.23; 95% CI: 0.87, 11.97, p = 0.08 and adjusted OR: 2.76; 95% CI: 0.89, 8.48, p = 0.07, respectively). CONCLUSION: Our findings emphasize the need for appropriate prevention and management of infections following kidney transplantation to avoid more serious problems, such as rejection, which could significantly raise the likelihood of allograft failure and probably death. Further studies with larger sample sizes are needed to investigate the impact of serum chloride levels prior to transplant and intraoperative hypotension on the risk of graft rejection and failure.

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.

The association between tocilizumab therapy and the development of thrombosis in critically ill patients with COVID-19: a multicenter, cohort study.

The use of tocilizumab for the management of COVID-19 emerged since it modulates inflammatory markers by blocking interleukin 6 receptors. Concerns regarding higher thrombosis risk while using tocilizumab were raised in the literature. The aim of this study is to investigate the association between tocilizumab therapy and the development of thromboembolic events in critically ill COVID-19 patients. A propensity score-matched, multicenter cohort study for critically ill adult patients with COVID-19. Eligible patients admitted to ICU between March 2020 and July 2021 were categorized into two sub-cohorts based on tocilizumab use within 24 h of ICU admission. The primary endpoint was to assess the incidence of all thrombosis cases during ICU stay. The secondary endpoints were 30-day mortality, in-hospital mortality, and the highest coagulation parameters follow-up (i.e., D-dimer, Fibrinogen) during the stay. Propensity score matching (1:2 ratio) was based on nine matching covariates. Among a total of 867 eligible patients, 453 patients were matched (1:2 ratio) using propensity scores. The thrombosis events were not statistically different between the two groups in crude analysis (6.8% vs. 7.7%; p-value = 0.71) and regression analysis [OR 0.83, 95% CI (0.385, 1.786)]. Peak D-dimer levels did not change significantly when the patient received tocilizumab (beta coefficient (95% CI): 0.19 (- 0.08, 0.47)), while there was a significant reduction in fibrinogen levels during ICU stay (beta coefficient (95% CI): - 0.15 (- 0.28, - 0.02)). On the other hand, the 30-day and in-hospital mortality were significantly lower in tocilizumab-treated patients (HR 0.57, 95% CI (0.37, 0.87), [HR 0.67, 95% CI (0.46, 0.98), respectively). The use of tocilizumab in critically ill patients with COVID-19 was not associated with higher thrombosis events or peak D-dimer levels. On the other hand, fibrinogen levels, 30-day and in-hospital mortality were significantly lower in the tocilizumab group. Further randomized controlled trials are needed to confirm our findings.

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.

The Impact of Midodrine Tapering Versus Nontapering Regimens on the Clinical Outcomes of Critically Ill Patients: A Retrospective Cohort Study.

BACKGROUND: Midodrine has been used in the intensive care unit (ICU) setting to reduce the time to vasopressor discontinuation. The limited data supporting midodrine use have led to variability in the pattern of initiation and discontinuation of midodrine. OBJECTIVES: To compare the effectiveness and safety of 2 midodrine discontinuation regimens during weaning vasopressors in critically ill patients. METHODS: A retrospective cohort study was conducted at King Abdulaziz Medical City. Included patients were adults admitted to ICU who received midodrine after being unable to be weaned from intravenous vasopressors for more than 24 hours. Patients were categorized into two subgroups depending on the pattern of midodrine discontinuation (tapered dosing regimen vs. nontapered regimen). The primary endpoint was the incidence of inotropes and vasopressors re-initiation after midodrine discontinuation. RESULTS: The incidence of inotropes or vasopressors' re-initiation after discontinuation of midodrine was lower in the tapering group (15.4%) compared with the non-tapering group (40.7%) in the crude analysis as well as regression analysis (odd ratio [OR] = 0.15; 95% CI = 0.03, 0.73, P = 0.02). The time required for the antihypertensive medication(s) initiation after midodrine discontinuation was longer in patients who had dose tapering (beta coefficient (95% CI): 3.11 (0.95, 5.28), P = 0.005). Moreover, inotrope or vasopressor requirement was lower 24 hours post midodrine initiation. In contrast, the two groups had no statistically significant differences in 30-day mortality, in-hospital mortality, or ICU length of stay. CONCLUSION AND RELEVANCE: These real-life data showed that tapering midodrine dosage before discontinuation in critically ill patients during weaning from vasopressor aids in reducing the frequency of inotrope or vasopressor re-initiation. Application of such a strategy might be a reasonable approach among ICU patients unless contraindicated.

Clinical pharmacy services in acute care setting during mass gatherings (Hajj): Insights from a task force.

BACKGROUND: Hajj is the largest mass gathering worldwide that takes place every year in Makkah, Saudi Arabia. This paper aims to provide a comprehensive guide and expectations for delivering and optimizing clinical pharmacy services during one of the largest mass gatherings in the world, Hajj pilgrimage METHODS: A task force initiated and included members of clinical pharmacists who previously participated in delivering clinical pharmacy services during the Hajj pilgrimage, members of the Saudi Society of Clinical Pharmacy (SSCP), and policymakers from different sectors and representatives from pharmaceutical care of the Ministry of Health (MOH). The members established an expert task force to conceptualize and draft the proposed suggestions highlighting the roles and responsibilities of clinical pharmacists during the annual Hajj season. RESULTS: The task force determined the following key domains 1) pharmaceutical care (administration and strategic plan, resources, formulary management); 2) pharmacists' activities (clinical pharmacy services and documentation, professional training and development, and staff credentials, and qualifications); 3) challenges and proposed solutions. The task force was divided into groups to draft each domain and provide suggested statements and insights for each section. Finally, the group members of the task force issued 15 opinion statements. CONCLUSION: Mass gatherings such as Hajj pilgrimage, represent a unique opportunity to demonstrate the value of pharmacists in advancing health care delivery within a multidisciplinary team. These suggestions and insights could guide the implementation of clinical pharmacy services in acute settings during mass gatherings (Hajj). Future studies should focus on assessing the applicability and the impact of the provided suggestions.

The Impact of Recombinant Human Erythropoietin Administration in Critically ill COVID-19 Patients: A Multicenter Cohort Study.

The use of erythropoietin-stimulating agents (ESAs) as adjunctive therapy in critically ill patients with COVID-19 may have a potential benefit. This study aims to evaluate the effect of ESAs on the clinical outcomes of critically ill COVID-19 patients. A multicenter, retrospective cohort study was conducted from 01-03-2020 to 31-07-2021. We included adult patients who were ≥ 18 years old with a confirmed diagnosis of COVID-19 infection and admitted to intensive care units (ICUs). Patients were categorized depending on ESAs administration during their ICU stay. The primary endpoint was the length of stay; other endpoints were considered secondary. After propensity score matching (1:3), the overall included patients were 120. Among those, 30 patients received ESAs. A longer duration of ICU and hospital stay was observed in the ESA group (beta coefficient: 0.64; 95% CI: 0.31-0.97; P = < .01, beta coefficient: 0.41; 95% CI: 0.12-0.69; P = < .01, respectively). In addition, the ESA group's ventilator-free days (VFDs) were significantly shorter than the control group. Moreover, patients who received ESAs have higher odds of liver injury and infections during ICU stay than the control group. The use of ESAs in COVID-19 critically ill patients was associated with longer hospital and ICU stays, with no survival benefits but linked with lower VFDs.

Real-world analysis of integration of sacubitril/valsartan into clinical practice in Saudi Arabia.

Despite the demonstrated advantages of angiotensin receptor/neprilysin inhibitors in the management of heart failure, the pivotal Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure (PARADIGM-HF) trial, which explored this class of medications, did not include individuals from Saudi Arabia. Recognizing that different nations and ethnic groups may exhibit unique characteristics, this study aimed to compare the demographics and outcomes of patients in Saudi Arabia who received sacubitril/valsartan (Sac/Val) with those enrolled in the PARADIGM-HF trial. In this retrospective, multicenter cohort study, we included all adult patients diagnosed with heart failure with reduced ejection fraction (HFrEF) within a tertiary healthcare system in Saudi Arabia between January 2018 and December 2021 and were initiated on Sac/Val. The primary objective was to compare the patient characteristics of those initiating Sac/Val treatment with the participants in the PARADIGM-HF trial. The secondary endpoints included the initiation setting, dose initiation, and titration, as well as alterations in B-type natriuretic peptide and ejection fraction at the 6-month mark. Furthermore, we reported the hospitalization and mortality event rates at the 12-month time point. The study included 400 patients with HFrEF receiving Sac/Val. Compared with the PARADIGM-HF trial, the cohort had a younger mean age and a higher prevalence of diabetes mellitus. SAC/VAL was prescribed as the initial therapy for 34% of the patients, while the remaining participants were initially treated with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker before transitioning to Sac/Val. Approximately 75% of patients were initiated on 100 mg Sac/Val twice daily, and 90% initiated therapy in the inpatient setting. The mean ejection fraction significantly improved from 26.5 ±â€…8.4% to 30.5 ±â€…6.4% at 6 months (P < .001), while the median B-type natriuretic peptide level change was not significant (P = .39). Our study revealed notable disparities in the baseline characteristics of patients with HFrEF compared with those in the PARADIGM-HF trial. These findings offer valuable real-world insights into the prescription patterns and outcomes of Sac/Val in patients with HFrEF in Saudi Arabia, an aspect not previously represented in the PARADIGM-HF study.

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.

The use of Tocilizumab in COVID-19 critically ill patients with renal impairment: a multicenter, cohort study.

Tocilizumab (TCZ) is recommended in patients with COVID-19 who require oxygen therapy or ventilatory support. Despite the wide use of TCZ, little is known about its safety and effectiveness in patients with COVID-19 and renal impairment. Therefore, this study evaluated the safety and effectiveness of TCZ in critically ill patients with COVID-19 and renal impairment. A multicenter retrospective cohort study included all adult COVID-19 patients with renal impairment (eGFR˂60 mL/min) admitted to the ICUs between March 2020 and July 2021. Patients were categorized into two groups based on TCZ use (Control vs. TCZ). The primary endpoint was the development of acute kidney injury (AKI) during ICU stay. We screened 1599 patients for eligibility; 394 patients were eligible, and 225 patients were included after PS matching (1:2 ratio); there were 75 TCZ-treated subjects and 150 controls. The rate of AKI was higher in the TCZ group compared with the control group (72.2% versus 57.4%; p = 0.03; OR: 1.83; 95% CI: 1.01, 3.34; p = 0.04). Additionally, the ICU length of stay was significantly longer in patients who received TCZ (17.5 days versus 12.5 days; p = 0.006, Beta coefficient: 0.30 days, 95% CI: 0.09, 0.50; p = 0.005). On the other hand, the 30-day and in-hospital mortality were lower in patients who received TCZ compared to the control group (HR: 0.45, 95% CI: 0.27, 0.73; p = 0.01 and HR: 0.63, 95% CI: 0.41, 0.96; p = 0.03, respectively). The use of TCZ in this population was associated with a statistically significantly higher rate of AKI while improving the overall survival on the other hand. Further research is needed to assess the risks and benefits of TCZ treatment in critically ill COVID-19 patients with renal impairment.

Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19-A multicenter cohort study.

Background: Despite insufficient evidence, vitamin D has been used as adjunctive therapy in critically ill patients with COVID-19. This study evaluates the effectiveness and safety of vitamin D as an adjunctive therapy in critically ill COVID-19 patients. Methods: A multicenter retrospective cohort study that included all adult COVID-19 patients admitted to the intensive care units (ICUs) between March 2020 and July 2021. Patients were categorized into two groups based on their vitamin D use throughout their ICU stay (control vs. vitamin D). The primary endpoint was in-hospital mortality. Secondary outcomes were the length of stay (LOS), mechanical ventilation (MV) duration, and ICU-acquired complications. Propensity score (PS) matching (1:1) was used based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analyses were employed as appropriate. Results: A total of 1,435 patients were included in the study. Vitamin D was initiated in 177 patients (12.3%), whereas 1,258 patients did not receive it. A total of 288 patients were matched (1:1) using PS. The in-hospital mortality showed no difference between patients who received vitamin D and the control group (HR 1.22, 95% CI 0.87-1.71; p = 0.26). However, MV duration and ICU LOS were longer in the vitamin D group (beta coefficient 0.24 (95% CI 0.00-0.47), p = 0.05 and beta coefficient 0.16 (95% CI -0.01 to 0.33), p = 0.07, respectively). As an exploratory outcome, patients who received vitamin D were more likely to develop major bleeding than those who did not [OR 3.48 (95% CI 1.10, 10.94), p = 0.03]. Conclusion: The use of vitamin D as adjunctive therapy in COVID-19 critically ill patients was not associated with survival benefits but was linked with longer MV duration, ICU LOS, and higher odds of major bleeding.

Evaluation of the use of methylprednisolone and dexamethasone in asthma critically ill patients with COVID-19: a multicenter cohort study.

BACKGROUND: Previous studies have shown mortality benefits with corticosteroids in Coronavirus disease-19 (COVID-19). However, there is inconsistency regarding the use of methylprednisolone over dexamethasone in COVID-19, and this has not been extensively evaluated in patients with a history of asthma. This study aims to investigate and compare the effectiveness and safety of methylprednisolone and dexamethasone in critically ill patients with asthma and COVID-19. METHODS: The primary endpoint was the in-hospital mortality. Other endpoints include 30-day mortality, respiratory failure requiring mechanical ventilation (MV), acute kidney injury (AKI), acute liver injury, length of stay (LOS), ventilator-free days (VFDs), and hospital-acquired infections. Propensity score (PS) matching, and regression analyses were used. RESULTS: A total of one hundred-five patients were included. Thirty patients received methylprednisolone, whereas seventy-five patients received dexamethasone. After PS matching (1:1 ratio), patients who received methylprednisolone had higher but insignificant in-hospital mortality in both crude and logistic regression analysis, [(35.0% vs. 18.2%, P = 0.22) and (OR 2.31; CI: 0.56 - 9.59; P = 0.25), respectively]. There were no statistically significant differences in the 30-day mortality, respiratory failure requiring MV, AKI, acute liver injury, ICU LOS, hospital LOS, and hospital-acquired infections. CONCLUSIONS: Methylprednisolone in COVID-19 patients with asthma may lead to increased in-hospital mortality and shorter VFDs compared to dexamethasone; however, it failed to reach statistical significance. Therefore, it is necessary to interpret these data cautiously, and further large-scale randomized clinical trials are needed to establish more conclusive evidence and support these conclusions.

Thromboprophylaxis in Hospitalized Non-Critically Ill Patients With Mild-to-Moderate COVID-19 Infection: A Systematic Review and Meta-Analysis.

The prevalence of venous thromboembolism is high in patients with COVID-19, despite prophylactic anticoagulation. The evidence that supports the preferred thromboprophylaxis regimen in non-critically ill patients with mild to moderate COVID-19 is still limited. Therefore, this systematic review and meta-analysis aimed to compare the clinical outcomes of hospitalized patients with mild to moderate COVID-19 who received standard thromboprophylaxis anticoagulation with intermediate to high prophylaxis regimens. We systematically searched MEDLINE and Embase databases for published studies until August 17th, 2022. We included studies on patients with mild to moderate COVID-19 who received thromboprophylaxis during their hospital stay. Patients who received standard prophylaxis dose "control group" were compared to patients who received intermediate to high prophylaxis "intervention group". Random effect models were used when pooling crude numbers and adjusted effect estimates of study outcomes. A comprehensive analysis was conducted, encompassing seven studies involving a total of 1931 patients. The risk of all-cause thrombosis was not statistically different between the two groups (risk ratio [RR] 1.48, 95% confidence interval [CI] [0.11, 20.21]). The risk of minor bleeding was reported to be lower in patients who received intermediate to high prophylaxis (RR 0.64, 95% CI 0.21, 1.97), while had a higher risk of major bleeding compared with the standard prophylaxis (RR 1.40, 95% CI 0.43, 4.61); however, did not reach the statistical significance. The overall risk for all hospital mortality favored the utilization of intermediate to high doses over the standard thromboprophylaxis dosing (RR 0.47, 95%CI 0.29, 0.75). In medically ill patients with COVID-19, there is no difference between standard and intermediate to high prophylaxis dosing regarding thrombosis and bleeding. However, it appears that intermediate to high prophylaxis regimens are linked to additional survival benefits.

Doxycycline's Potential Role in Reducing Thrombosis and Mortality in Critically Ill Patients With COVID-19: A Multicenter Cohort Study.

Doxycycline has revealed potential effects in animal studies to prevent thrombosis and reduce mortality. However, less is known about its antithrombotic role in patients with COVID-19. Our study aimed to evaluate doxycycline's impact on clinical outcomes in critically ill patients with COVID-19. A multicenter retrospective cohort study was conducted between March 1, 2020, and July 31, 2021. Patients who received doxycycline in intensive care units (ICUs) were compared to patients who did not (control). The primary outcome was the composite thrombotic events. The secondary outcomes were 30-day and in-hospital mortality, length of stay, ventilator-free days, and complications during ICU stay. Propensity score (PS) matching was used based on the selected criteria. Logistic, negative binomial, and Cox proportional hazards regression analyses were used as appropriate. After PS (1:3) matching, 664 patients (doxycycline n = 166, control n = 498) were included. The number of thromboembolic events was lower in the doxycycline group (OR: 0.54; 95% CI: 0.26-1.08; P = .08); however, it failed to reach to a statistical significance. Moreover, D-dimer levels and 30-day mortality were lower in the doxycycline group (beta coefficient [95% CI]: -0.22 [-0.46, 0.03; P = .08]; HR: 0.73; 95% CI: 0.52-1.00; P = .05, respectively). In addition, patients who received doxycycline had significantly lower odds of bacterial/fungal pneumonia (OR: 0.65; 95% CI: 0.44-0.94; P = .02). The use of doxycycline as adjunctive therapy in critically ill patients with COVID-19 might may be a desirable therapeutic option for thrombosis reduction and survival benefits.

When antivirals backfire: An evaluation of favipiravir's clinical outcomes in critically ill patients with COVID-19: A multicenter cohort study.

BACKGROUND: Favipiravir is an oral antiviral, that might treat COVID-19 by enhancing viral eradication, particularly in patients with mild-to-moderate disease. Yet, the findings on the use of favipiravir in critically ill patients with COVID-19 are inconsistent. Therefore, this study aimed to assess the effectiveness and safety of favipiravir in critically ill patients with COVID-19. METHOD: A multicenter retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) was conducted from March 2020 to July 2021. Patients were categorized based on favipiravir use (control vs. favipiravir). The primary outcome was in-hospital mortality. Secondary outcomes included mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during the stay. RESULTS: After propensity score (PS) matching (1:1 ratio), 146 patients were included in the final analysis. A higher in-hospital and 30-day mortality were observed in patients receiving favipiravir compared to the control group at crude analysis (65.3% vs. 43.8%; P-value=0.009 and 56.3% vs. 40.3; P-value=0.06, respectively); however, no differences were observed using multivariable Cox proportional hazards regression analysis (HR 1.17; 95% CI 0.73, 1.87; P-value =0.51 and HR 0.86; 95% CI 0.53, 1.39; P-value=0.53, respectively). Conversely, the MV duration and ICU LOS were longer in patients who received favipiravir than the control group (ß coefficient 0.51; CI 0.09, 0.92; P-value = 0.02, ß coefficient 0.41; CI 0.17, 0.64; P-value = 0.0006, respectively). Complications during the stay were comparable between the two groups. CONCLUSION: The use of favipiravir in critically ill patients with COVID-19 did not demonstrate a reduction in mortality; instead, it was linked with longer MV duration and ICU stay. This finding suggests limiting favipiravir use to infections where it is more effective, other than COVID-19. Further randomized clinical trials are needed to confirm these findings.