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

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

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

BackgroundDespite 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.MethodsA 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.ResultsA 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].ConclusionThe 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

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 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

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

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

Abstract 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

Comparative Effectiveness of Apixaban and Rivaroxaban Lead-in Dosing in VTE Treatment: Observational Multicenter Real-World Study

Apixaban and rivaroxaban require lead-in dosing for 7 and 21 days, respectively, when treating venous thromboembolism (VTE). However, no evidence exists to support subtracting parenteral anticoagulation days from total lead-in dosing. A multicenter study was conducted, including adult patients with acute VTE who received apixaban or rivaroxaban. The patients were grouped as follows. The recommended group received oral lead-in anticoagulant for the full recommended duration. The mixed group received lead-in therapy as parenteral with oral anticoagulant. The incidence of recurrent VTE (rVTE) and major bleeding (MB) within 90 days were the main outcomes. Of the 368 included patients, 47.8% received apixaban, and 52.2% received rivaroxaban. The recommended lead-in was used in 296 patients (80.4%), whereas 72 (19.6%) received the mixed-lead-in regimen. Five patients had rVTE events within 90 days; two occurred during hospitalization in the recommended group versus none in the mixed group (0.7% vs. 0.0%; p = 1.000). After discharge, two events occurred in the recommended group and one in the mixed group (0.7% vs. 1.4%; p = 0.481). In terms of MB, 24 events occurred in 21 patients within 90 days. During hospitalization, 11 events occurred in the recommended group and seven in the mixed group (3.7% vs. 9.7%; p = 0.060). After discharge, five more events occurred in the recommended group and one in the mixed group (1.4% vs. 1.7%; p = 1.000). The mixed-lead-in regimen is safe and effective in comparison with the recommended-lead-in regimen

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, I 2  = 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, I 2  = 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, I 2  = 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

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

BackgroundThe 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.MethodsThis 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.ResultsA 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%).ConclusionAlthough 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