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 prevalence of cardiovascular diseases, chronic kidney disease, and obesity in patients with type 2 diabetes mellitus and the description of concurrent treatments: A two-center retrospective cross-sectional study in Saudi Arabia.

Background: Atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and obesity are associated with increased morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Nonetheless, their prevalence among patients with T2DM in Saudi Arabia (SA) remains unknown. As current guidelines recommend, these comorbidities require adding certain antidiabetic agents with cardiorenal benefits. However, the prescribers' adherence to these recommendations remains unclear. Methods: A two-center retrospective cross-sectional study was conducted including adult patients (≥18 years) with T2DM admitted to hospital or seen at outpatient clinics between January and December 2020. Patients were classified into two groups based on the presence or absence of ASCVD. Patients with no prior ASCVD history were further classified based on the 10-year ASCVD risk estimation. Endpoints of interest included the prevalence of ASCVD, HF, CKD, and obesity in patients with T2DM. We also evaluated the characteristics of the utilized antidiabetic agents, statin, and aspirin therapies.. Results: Of the 1,218 included patients with T2DM, the majority were female (57.0 %), and aged 45-64 years (53.0 %) with a mean age of 59.3 ± 13.1 years. Hypertension and dyslipidemia were the most prevalent comorbidities (67.7 % and 69.0 %, respectively). Among all patients, 18.6 % had an established ASCVD and the prevalence of HF, CKD, and obesity were 5.1 %, 8.7 %, and 58.3 %, respectively. The most common types of ASCVD witnessed were revascularization (42.3 %), myocardial infarction (36.6 %), and stroke (33.9 %); with an increased prevalence of ASCVD as the age increases (52.8 % at age ≥ 65 years). In the non-ASCVD group, the 10-year ASCVD risk was intermediate or high in 62.7 % of these patients. The rates of utilization of guidelines-recommended therapies were 83.6 % for metformin, 9.4 % for GLP-1 RA, 10.8 % for SGLT2i, 35.2 % for aspirin alone or in combination with clopidogrel, and 79.7 % for statin therapy. Conclusions: ASCVD, HF, CKD, and obesity are common complications in patients with T2DM in SA, with low overall utilization of the recommended guidelines-recommended medical therapies. Multimodal strategies should be utilized to assess T2DM and its complications, and to improve prescribers' adherence to guidelines-recommended therapies.

Team-based learning versus traditional teaching effect on pharmacy Students' Performance: A systematic review and Meta-Analysis.

Background: Several pharmacy schools have implemented team-based learning (TBL) in their curriculum worldwide. Yet, TBL's effectiveness compared to traditional teaching in improving students' outcomes in pharmacy education is yet to be assessed collectively. Thus, the aim of this meta-analysis is to compare the performance of pharmacy students following the implementation of team-based learning (TBL) in the pharmacy curriculum as opposed to traditional learning methods. Methods: This systematic review and meta-analysis included studies that assessed students' performance after TBL was implemented in a pharmacy curriculum. Adhering to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, the review conducted searches in Embase, MEDLINE, and Google Scholar until July 26, 2023. Results: A total of 11 studies comparing TBL against traditional teaching methods and assessing students' performance were included. The pooled analysis, involving 2,400 students from 10 studies, demonstrated a mean difference (MD) in favor of TBL (MD = 2.27, 95 % CI [-0.85, 5.40]). However, notable heterogeneity was observed with an I2 value of 82 %, and the observed difference did not reach statistical significance. Conclusion: TBL exhibited enhanced student performance in pharmacy education compared to traditional teaching, although the difference was not statistically significant. The meta-analysis findings support the use of TBL in pharmacy education for various pharmacy courses (pharmaceutical and clinical sciences courses) and students at different levels. However, there is a need for more robust studies to comprehensively evaluate TBL, considering aspects such as students' performance and engagement, skills development, and satisfaction.

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.

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 impact of Saudi Arabia - United States clinical pharmacy post-graduate training programs agreements on clinical pharmacy faculty in Saudi universities: A retrospective descriptive study focused on history and future recommendations.

Background: There has been a growing demand for clinical pharmacy services in the Kingdom of Saudi Arabia (KSA) in the past 3 decades. The Ministry of Education has established agreements with several institutions in the United States to secure clinical pharmacy residency and research fellowship programs opportunities for Saudi scholars. The aims of this study were to describe the Saudi scholars' clinical pharmacy training pathways and their contribution to the pharmacy profession in KSA. Methods: This is a retrospective, descriptive study conducted on clinical pharmacy faculty in governmental Saudi universities who graduated from the US until 2023. The study outcomes included the post-graduate year-1 (PGY-1) residency match rate, post-graduate year-2 (PGY-2) acceptance rate, the PGY-2 specialties of Saudi scholars, and the number of clinical pharmacy programs established in KSA. Results: In total, 115 Saudi scholars have pursued clinical pharmacy pathway in the US. The PGY-1 residency match rate was 80 % (92/115). In contrast, the PGY-2 acceptance rate was 60.9 % (70/115). The most common PGY-2 specialty was in infectious diseases (N = 17; 24 %). Two pharmacy colleges had established residency programs and 1 pharmacy college had established a research fellowship. Conclusion: The Ministry of Education's efforts for clinical pharmacy program agreements were fundamental for advancing clinical pharmacy in Saudi universities. A significant number of Saudi scholars returned to KSA with clinical pharmacy degrees. There are more opportunities for further development, including expanding the clinical pharmacy program collaboration in the US and increasing the number of residency and research fellowship positions in KSA.

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.

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.

Evaluation of the Safety and Effectiveness of Topical Intrapleural Application of Tranexamic Acid in Thoracic Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Bleeding remains a common complication post-thoracic surgery. Although intravenous tranexamic acid (TXA) has been shown to decrease blood loss, its use has been associated with adverse effects. Accordingly, topical TXA has been proposed as an alternative to reduce bleeding with fewer systemic complications. METHODS: We searched Medline, Embase, and Cochrane Central databases for randomized controlled trials (RCTs) comparing topical TXA versus control (i.e., placebo) in patients undergoing thoracic procedures. The primary outcome was total postoperative blood loss at 24 hours. Secondary outcomes included were the number of red blood cell (RBC) transfusions, and hospital length of stay (LOS). Meta-analyses were pooled using mean difference with inverse-variance weighting and random-effects. RESULTS: Out of the 575 unique studies that were screened, we identified three randomized controlled trials (RCTs) involving 399 patients. Out of the three RCTs analyzed, two studies, accounting for 67% of the total, were found to have a low risk of bias. The primary outcome of 24-h post-operative blood loss was significantly lower in patients who received TXA (mean difference [MD] -93.6 ml, 95% CI -121.8 to -65.4 ml, I2 = 45%). In addition, the need for RBC transfusion was significantly lower in the topical TXA group compared to control (MD -0.5 units, 95% CI -0.8 to -0.3 units, I2 = 60%). However, there was no significant difference in the hospital length of stay (LOS) (MD -0.3 days, 95% CI -0.9 to 0.4 days, I2 = 0%). These results remained consistent after several sensitivity analyses. The use of topical intrapleural tranexamic acid has also been found to be safe without any significant safety concerns. CONCLUSION: Topical intrapleural TXA reduces blood loss and the need for blood transfusions during thoracic surgery. In addition, there is no evidence of the increased safety concerns associated with its use. Larger trials are necessary to validate these findings and evaluate the safety and efficacy of different dosages.

Cardiovascular adverse events of antineoplastic monoclonal antibodies among cancer patients: real-world evidence from a tertiary healthcare system.

BACKGROUND: Antineoplastic monoclonal antibodies (mAbs), such as trastuzumab, bevacizumab, and pertuzumab have been the mainstay of therapy in cancer patients. Despite proven efficacy of the monoclonal antibodies, cardiovascular-induced adverse events such as heart failure, hypertension, ischemic heart disease, arrhythmias, thromboembolic events, and hemorrhage remain a major complication. The European society of cardiology address that concern with antineoplastic monoclonal antibodies issuing a guideline to manage and monitor chemotherapy-induced cardiotoxicity. There is limited evidence of the real-world prevalence of cardiovascular (CV) events induced by monoclonal antibodies among patients with cancer in Saudi Arabia. OBJECTIVE: To evaluate the prevalence of cardiovascular adverse events among patients with cancer treated with monoclonal antibodies in Saudi Arabia. METHODS: This is a retrospective study conducted in a tertiary care hospital, Riyadh, Saudi Arabia. Data were obtained from an electronic medical record of patients with cancer treated with one of the selected monoclonal antibodies, who met the inclusion criteria between January 2005 until June 2015 and have been followed up for at least one year. Patients were stratified into groups according to monoclonal antibodies treatment: trastuzumab, bevacizumab, pertuzumab, and combined mAbs. RESULTS: A total of 1067 patient were included in the study, within the pre-determined study period. The prevalence of cardiovascular disease among patients with cancer treated with monoclonal antibodies was 16.3%. The prevalence of heart failure was relatively higher in the trastuzumab group (46/626 patients, 7.3%). Among 418 patients treated with bevacizumab, hypertension was the most frequent adverse event, reported in 38 patients (9.1%), followed by thromboembolism reported in 27 patients (6.5%). Treatment discontinuation owing to cardiovascular adverse events was reported in 42/1,067 patients (3.9%). CONCLUSION AND RELEVANCE: Prevalence of antineoplastic monoclonal antibody induced cardiovascular adverse events among patients with cancer is substantially high in Saudi Arabia. There is an urgent need to streamline the practice for identifying high risk patients and flexible referral system for cardio-oncology care.

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.

Clinical characteristics and dosing of apixaban and rivaroxaban for the management of venous thromboembolism: A multi-center retrospective observational study.

Background: Since the risk of recurrence of venous thromboembolism (VTE) increases with duration or inadequate anticoagulation dosage, a proper regimen of apixaban and rivaroxaban is essential in patients with VTE, especially during the acute phase. This study aims to describe the clinical characteristics and dosing of anticoagulants for patients who received apixaban or rivaroxaban for VTE treatment. Methods: The multi-center retrospective observational study included patients diagnosed with VTE who had received apixaban or rivaroxaban between January 1, 2016, and December 31, 2021. The study's description of real-world practices includes patients' characteristics, along with anticoagulant dose and duration used for lead-in or maintenance therapy to manage VTE. Results: The study involved 695 patients with VTE; 342 of whom were treated with apixaban (49.2%), while 353 were treated with rivaroxaban (50.8%). During the acute phase, 30.1% and 19.3% of patients did not receive lead-in therapy with apixaban and rivaroxaban, respectively, and 1.2% received reduced doses of either medication. Among the patients who received apixaban alone for lead-in, the majority (79.5%) received the recommended duration, while 17.1% received a shorter lead-in duration (≤5 days), with an overall mean duration of 6.5 days. Most patients who received rivaroxaban alone for lead-in (93.0%) received the drug for the recommended duration, with an overall mean duration of 20.2 days. Most of the patients who did not receive apixaban or rivaroxaban for lead-in used parenteral anticoagulants for varying durations; however, around 25.0% of these patients did not receive any lead-in anticoagulant and started on maintenance therapy. Overall, patients who did not receive apixaban or rivaroxaban lead-in therapy were commonly associated with a higher risk of bleeding according to their clinical characteristics. Conclusion: A notable proportion of patients with VTE who were mostly at low to intermediate risk of bleeding received non-recommended doses or durations of apixaban or rivaroxaban for lead-in therapy. Large studies are needed to establish evidence about the outcomes associated with these practices.

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.

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.

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.

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.

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.

Clinical Pharmacy Faculty Provision of Direct Patient Care, Challenges, and Opportunities.

Background: The quadripartite mission of clinical track faculty members involves research, teaching, services, and direct patient care. However, the extent of faculty involvement in direct patient care remains a challenge. Thus, the study's objective is to evaluate the effort spent on direct patient care by clinical faculty of pharmacy schools in Saudi Arabia (S.A.) and identify factors that hinder or facilitate providing direct patient care services. Methods: This multi-institutional, cross-sectional questionnaire study conducted between July 2021 and March 2022 involved several pharmacy schools' clinical pharmacy faculty members in S.A. The primary outcome was the percentage of time/effort spent on patient care services and other academic responsibilities. The secondary outcomes were the factors affecting the effort spent on direct patient care and the barriers preventing the provision of clinical services. Results: A total of 44 faculty members took the survey. The percentage of effort spent on clinical education was highest at a median (IQR) of 37.5 (30, 50), followed by that spent on patient care [19 (10, 28.75)]. The percentages of effort spent on education and the length of academic experience were negatively associated with efforts spent on direct patient care. The most commonly reported barrier affecting fulfilling patient care duties was the lack of a clear practice policy (68%). Conclusion: Although most clinical pharmacy faculty members were involved in direct patient care, half of them devoted only 20% or less of their time to it. An effective effort allocation for clinical faculty duties will require the development of a clinical faculty workload model that sets realistic expectations about the time spent on clinical and non-clinical duties.