Safety and Effectiveness of Direct Oral Anticoagulants Versus Warfarin in Patients with Venous Thromboembolism using Real-World Data: A Systematic Review and Meta-Analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have shown comparable efficacy and a superior safety profile in clinical trials for patients with venous thromboembolism (VTE). However, further study is needed to assess DOACs' effectiveness and safety compared to warfarin in a real-world context. Thus, this meta-analysis compares the effectiveness and safety of warfarin and DOACs in patients with VTE. METHOD: A systematic review of the literature using PubMed and EMBASE was conducted from inception until June 2024. We examined observational studies that compared safety and effectiveness between DOACs and warfarin when used in treating VTE and reported adjusted hazard ratios (HRs) and/or odds ratios (ORs) for recurrent VTE, major bleeding, clinically relevant non-major bleeding, gastrointestinal bleeding, intracranial hemorrhage, and death from any cause. We then estimated the pooled effect using the random-effects model for meta-analysis. RESULTS: A total of 25 studies were included in the current meta-analysis. DOAC therapy was associated with significantly lower risks of recurrent VTE (HR 0.76, 95% confidence interval [CI] 0.69-0.85), major bleeding (HR 0.77, 95% CI 0.72-0.83), clinically relevant non-major bleeding (HR 0.82, 95% CI 0.77-0.88), and gastrointestinal bleeding (HR 0.75, 95% CI 0.68-0.83) compared to warfarin. However, no statistically significant difference was observed in all-cause mortality between the two groups (HR 0.96, 95% CI 0.83-1.10). CONCLUSION: This meta-analysis found that DOACs are associated with a significant reduction in VTE recurrence in addition to the known favorable safety profile when compared to warfarin.

Evaluating the use of paracetamol to prevent fasting headache during the first week of Ramadan: A randomized, open-label, clinical trial.

BACKGROUND: Fasting headaches frequently occur during the first few days of Ramadan, and treatment is challenging because of fasting. OBJECTIVE: This study aimed to evaluate the effect of extended-release paracetamol on preventing fasting headaches. METHODS: A randomized, open-label clinical trial investigated the efficacy of extended-release paracetamol at a daily dose of 1330 mg in preventing fasting headache. Adults aged 18 years and older were recruited through the Clinical Trial Unit at the King Saud University Medical City. The eligible participants in the study fasted 13.5 h daily during the first week of Ramadan. Participants in the treatment and control arms were followed up to investigate the occurrence, severity, and timing of headache symptoms via self-reporting using a standardized headache diary scale with a daily online link or phone call. The primary outcome was the frequency of headache episodes while fasting during the first week of Ramadan. RESULTS: A total of 238 participants were enrolled and randomized. Of these, 173 followed the protocol (80 treated, 93 control) for at least the first day and were included in the analysis. Most participants were young and healthy, with a mean age of 32.2 ± 10.2 years. More men were included in the study (102/173; 59.0%), a small proportion of participants were smokers (31/173; 17.9%), and almost all participants reported being coffee drinkers (165/173; 95.4%); nonetheless, these characteristics were evenly distributed between the two groups in the study. The overall incidence of headache episodes was 33.0% (57/173) on day 1 and decreased to 11.3% (18/159) on day 7. On average over the 7 days, no significant effect was observed for the treatment on the incidence of headache, as the findings from the generalized estimating equation model indicated (ß = -0.398, p = 0.084; odds ratio = 0.67, 95% confidence interval [CI] 0.42-1.06). Moreover, there was initially no significant difference in the incidence of headache episodes between the treatment and control groups. However, the treatment group had significantly fewer headache episodes during fasting than the control group on day 3 (4/72 [5.6%] vs. 15/91 [16.5%], p = 0.031; relative risk [RR] = 0.34, 95% CI 0.12-0.97) and day 6 (5/69 [7.2%] vs. 20/90 [22.2%], p = 0.010; RR = 0.33, 95% CI 0.13-0.82). No adverse effects were observed during the study period. CONCLUSION: No significant differences were observed in the occurrence of fasting headaches between the two groups on most days during the study period. Additional studies are required to address fasting headaches during the first week of Ramadan.

Overview of online pharmacy regulations in Saudi Arabia and the Gulf cooperation council countries and their impact on online pharmacy service providers in Saudi Arabia: a qualitative analysis.

Background: Laws and regulations are needed to regulate the growing online pharmacy (OP) services. The main objective of this work was to provide an overview of the laws and regulations for OP services in the Gulf Cooperation Council (GCC) countries. In addition, the perception of how these laws and regulations in Saudi Arabia (SA) affect the online ordering of medications and health-related products from national and international OPs was explored. Methods: A secondary data collection through emails and a qualitative descriptive analysis was used to gain insight into the OP regulations in the GCC countries. Then, a qualitative study was carried out with semi-structured interviews to investigate the impact of these regulations on the practice and the market from the OP service providers' perspective. The interviews were carried out with a sample of major OP service providers in SA, to represent the GCC countries. During the interviews, multiple open-ended questions were used to explore opinions about the OP regulations and how these regulations affected the practice. The interviews were then transcribed and thematically analysed. Results: Responses were mainly received from regulators in SA, Bahrain, Oman and United Arab Emirates (UAE). SA and UAE allow for offering of OP services as add-on service for existing community pharmacy, while UAE also allows for standalone OP providers. SA, Bahrain, and Oman allow online ordering of both over-the-counter (OTC) and prescription-only medications (POM) from international OP; a prescription is required for POM and quantities allowed should be no more than 3 months' supply in case of SA and Oman while this was not specified in case of Bahrain. Invoice of purchase was also required for any POM to be released from customs in SA and Bahrain but not in Oman and UAE. Controlled medications were prohibited to be ordered online in SA, UAE, and Bahrain while it was allowed in Oman if the prescription was issued within 6-month, and the quantity dispensed was for 1 month only. Apart from online ordering of medications in these countries, no specific regulations existed to regulate ordering of other health-related products from local or international OPs. Whether Kwait and Qatar have regulations for OP could not be established due to lack of response. Two of the four interviewed representatives of OP service providers in SA were not aware of the existence of specific regulations for OP services. The representatives who were aware of these regulations were satisfied with them and found them beneficial for their business and for the patients at the same time. However, representatives raised concerns regarding the enforcement of regulations on international OP providers. Conclusion: The existing regulations for online ordering of medications are somewhat comparable between the GCC countries, with no specific regulations for ordering of other health-related products from local or international OPs. In SA, there is limited awareness of the existing regulations for OP services by providers. Nevertheless, the need for detailed regulations on certain aspects of OP services was highlighted, such as regulations for international OPs and importing medications for personal use.

Descriptive Analysis of Adverse Events Reported for New Multiple Myeloma Medications Using FDA Adverse Event Reporting System (FAERS) Databases from 2015 to 2022.

BACKGROUND: New multiple myeloma (MM) medications have revolutionized the treatment landscape, but they are also associated with a range of adverse events (AEs). This study aims to provide a comprehensive overview of AEs reported for four new MM medications: daratumumab, ixazomib, elotuzumab, and panobinostat. METHODS: This study uses a descriptive retrospective approach to analyze the FDA Adverse Event Reporting System (FAERS) from 2015 to 2022. It includes variables like medication names, report details, patient demographics, adverse events, and reporter types. The initial dataset consists of over 3700 adverse events, which are categorized into 21 groups for clarity and comparison. RESULTS: The FAERS database revealed 367,756 adverse events (AEs) associated with novel multiple myeloma drugs from 2015-2022. Ixazomib had the highest number of reported AEs with 206,243 reports, followed by daratumumab with 98,872 reports, then elotuzumab with 26,193 AEs. Ixazomib's AE reports increased dramatically over the study period, rising approximately 51-fold from 1183 in 2015 to 60,835 in 2022. Of the medications studied, ixazomib also recorded the highest number of deaths (24,206), followed by daratumumab (11,624), panobinostat (7227), and elotuzumab (3349). The majority of AEs occurred in patients aged 55-64 and 65-74 years. CONCLUSIONS: Ixazomib, a new MM medication, had the highest number of AEs reported. Also, it has the highest rate of reported deaths compared to other new MM medications. Clinicians should be aware of the potential AEs associated with this medication and further research is needed to understand the reasons for the high number of AEs and to develop mitigation strategies. More attention should also be paid to the safety of new multiple myeloma medications in younger patients.

Liraglutide's Effect on Weight Management in Subjects With Pre-diabetes: A Systematic Review & Meta-Analysis.

BACKGROUND: Despite the growing literature, the effectiveness of liraglutide in weight management among individuals with prediabetes and in preventing the disease remains controversial. This study aims to critically evaluate the extent of liraglutide's impact on weight management in this population and assess the heterogeneity among extant studies. METHODS: A systematic literature search was conducted across MEDLINE, Embase, ClinicalTrials.gov, and the reference list of retrieved studies to identify eligible English language randomized controlled trials evaluating liraglutide's effect on weight in individuals with pre-diabetes. Non-randomized studies, studies not reporting relevant outcomes, and those conducted on patients with type 2 diabetes were excluded from this review. Outcomes included a change from baseline in absolute body weight in kg, body mass index (BMI), waist circumference, glycosylated hemoglobin (HbA1c), and low-density lipoprotein cholesterol levels. Additional safety outcomes were also reported. Data were analyzed using R statistical software version 4.3.1. A fixed-effect model was used when pooling crude numbers for study outcomes. Moreover, a sensitivity analysis using random-effect model was performed and heterogeneity was assessed using I2 statistics. RESULTS: Five eligible studies were included, with a total of 1604 subjects in the liraglutide arm and 859 subjects in the control arm. Participants exposed to liraglutide showed a decrease in body weight (mean difference [MD] = -4.95 kg; 95% CI -5.16, -4.73; I2 = 93%), BMI (MD = -2.06 kg/m2; 95%CI -2.22, -1.89; I2 = 97%), waist circumference (MD = -4.61 cm; 95% CI -4.79, -4.43; I2 = 82%), HbA1c (MD = -0.33%; 95%CI -0.34, -0.31; I2 = 100%), and low-density lipoprotein cholesterol levels (MD = -0.36 mmol/L; 95% CI -0.39, -0.33; I2 = 99%). The overall effect size remained similar when using a random-effects model for all outcomes. In addition, the rate of adverse events was higher with liraglutide when compared to the control; however, the dropout rates were relatively lower in the former arm. CONCLUSION: While our meta-analysis suggests that liraglutide can reduce body weight, BMI, waist circumference, and HbA1c levels in individuals with pre-diabetes, the findings should be interpreted cautiously due to limitations such as the small number of trials and their short duration, and variability in dosages. Further randomized controlled trials examining long-term outcomes are essential to validate these findings and address the high heterogeneity among the studies included in this analysis.

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.

Clinical pharmacists' knowledge, attitude, perception, and beliefs about the role of pharmacogenetic testing for genes polymorphisms when prescribing mercaptopurine.

Background: Single nucleotide polymorphisms in the gene encoding proteins involved in mercaptopurine metabolism can influence drug efficacy and safety. This study aims to assess clinical pharmacists' knowledge about mercaptopurine-related genes and their polymorphisms and investigate their attitudes, perceptions, and beliefs about the need for and importance of pharmacogenetic testing for mercaptopurine. Methods: A cross-sectional descriptive study was conducted among oncology/hematology clinical pharmacists in Saudi Arabia using an online-questionnaire developed by experts in the field. The questionnaire consists of four-sections exploring clinical pharmacists' knowledge, attitudes, perceptions, and beliefs about the importance of gene testing and genes polymorphism when prescribing mercaptopurine. Descriptive statistics were used to analyze the data in the study. Results: A total of 41 oncology/hematology clinical pharmacists responded to the survey invitation. Almost half of them had more than 10 years of work experience, but only 17 % of them received formal training in pharmacogenetics. The overall level of knowledge about pharmacogenetics among participants was low, with a mean score of 2.8 points (1.7) out of 8 items. However, around 76 % agreed that it is important to perform pharmacogenetic screening prior to prescribing mercaptopurine, and almost 93 % state that it will influence their dosage recommendation. Most of the participants had a good perception (95.1 %) of their role in genetic testing for medication selection, dosing, and monitoring; however, about 10 % of surveyed pharmacists reported not being completely responsible about recommending pharmacogenetic testing. The surveyed pharmacists had a good belief in the importance of pharmacogenetic testing and their overall attitude was positive toward the use of pharmacogenetic testing, with emphasis on the importance of training on the proper assessment and interpretation of pharmacogenetic tests. Conclusions: Pharmacists demonstrated good perception and positive attitude toward pharmacogenetic testing, despite the low level of knowledge and limited formal training. Thus, more attention to developing national guidelines on pharmacogenetic testing is warranted to ensure successful pharmacogenetic testing implementation.

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.

Assessment of Knowledge and Practice of Healthcare Providers in Saudi Arabia Regarding Clostridioides difficile Infection Diagnosis and Management: A Cross-Sectional Questionnaire-Based Study.

Introduction: Diagnosis of Clostridioides difficile infection (CDI) depends on clinical presentation and laboratory testing. Stool diagnostic tests are essential for effective detection of toxigenic C. difficile strains. No study to date has evaluated the readability of microbiology labs in Saudi Arabia to test for CDI and evaluated the knowledge and practice of healthcare providers regarding CDI management. Therefore, this study aimed to assess the knowledge and practice of healthcare providers in Saudi Arabia regarding CDI diagnosis and treatment. Methods: A cross-sectional, descriptive, questionnaire-based study was conducted on healthcare providers in Saudi Arabia, primarily physicians and clinical pharmacists. The questionnaire was developed based on a literature review and input from infectious diseases experts. The questionnaire was administered online. Data were analyzed using descriptive and inferential statistics. Results: Of 183 respondents, 27.9% had adequate knowledge on CDI diagnosis and management. The majority were internal medicine specialists (37.7%) working in governmental or semi-governmental hospitals (80.9%) in central (46.6%) or southern (30.1%) regions of Saudi Arabia. Most participants assessed laxative use (86.3%) and reported positive C. difficile specimens to infection control (67.2%). However, knowledge varied, with 57.4% supporting unnecessary retesting and 53% assuming positive PCR test indicates moderate CDI probability. Factors such as specialization, hospital accreditation status, and bed capacity influenced knowledge levels (p<0.01 for all factors). Conclusion: The study revealed a significant knowledge gap among Saudi healthcare providers regarding CDI diagnosis, management, and severity classification, highlighting the need for improved education and adherence to guidelines to improve patient outcomes and reduce recurrence risks.

Effects of Beta Lactams on Behavioral Outcomes of Substance Use Disorders: A Meta-Analysis of Preclinical Studies.

INTRODUCTION: Preclinical studies demonstrated that beta-lactams have neuroprotective effects in conditions involving glutamate neuroexcitotoxicity, including substance use disorders (SUDs). This meta-analysis aims to analyze the existing evidences on the effects of beta-lactams as glutamate transporter 1 (GLT-1) upregulators in animal models of SUDs, identification of gaps in the literature, and setting the stage for potential translation into clinical phases. METHODS: Meta-analysis was conducted on preclinical studies retrieved systematically from MEDLINE and ScienceDirect databases. Abused substances were identified by refereeing to the National Institute on Drug Abuse (NIDA). The results were quantitatively described with a focus on the behavioral outcomes. Treatment effect sizes were described using standardized mean difference, and they were pooled using random effect model. I2-statistic was used to assess heterogeneity, and Funnel plot and Egger's test were used for assessment of publication bias. RESULTS: Literature search yielded a total of 71 studies that were eligible to be included in the analysis. Through these studies, the effects of beta-lactams were evaluated in animal models of nicotine, cannabis, amphetamines, synthetic cathinone, opioids, ethanol, and cocaine use disorders as well as steroids-related aggressive behaviors. Meta-analysis showed that treatments with beta-lactams consistently reduced the pooled undesired effects of the abused substances in several paradigms, including drug-self administration, conditioned place preference, drug seeking behaviors, hyperlocomotion, withdrawal syndromes, tolerance to analgesic effects, hyperalgesia, and hyperthermia. CONCLUSION: This meta-analysis revealed that enhancing GLT-1 expression in the brain through beta-lactams seemed to be a promising treatment approach in the context of substance use disorders, as indicated by results in animal models.

Acute kidney injury associated with piperacillin-tazobactam versus other antibiotics combined with vancomycin in critically ill patients: A retrospective cohort study.

Introduction: Evidence of acute kidney injury (AKI) induced by piperacillin-tazobactam (Piptazo) versus other broad-spectrum antibiotics (BSA) combined with vancomycin has been established in the literature. However, there is limited evidence regarding these combinations among critically ill patients. This study assessed the risk of nephrotoxicity of Piptazo versus other BSA as an add-on to vancomycin among patients admitted to an intensive care unit (ICU). Methods: We have reviewed patients' charts retrospectively to investigate AKI incidence among ICU patients receiving Piptazo versus other BSA as an add-on to vancomycin. Furthermore, we have assessed the duration of AKI and ICU stay, as well as the association between patients' criteria and risk of AKI using logistic regression analyses. Results: A total of 79 patients were included, 50 patients received the Piptazo combination while 29 patients received other BSA combinations. Almost 52 % of the patients in the Piptazo group developed AKI while only 37.9 % of those in the BSA group did, yet the difference was not statistically significant (p = 0.22). On the other hand, the risk of AKI was highly associated with vancomycin trough concentration above 20 mcg/mL, nephrotoxic medications, and African descent (OR 7.1, 95 %CI 1.96-25.84, OR 3.94, 95 %CI 1.27-12.2, OR 3.53, 95 %CI 1.1-11.27, respectively). Conclusion: Although the difference in AKI risk was not statistically significant between Piptazo versus BSA groups, the elevated trough concentration of vancomycin and the concomitant use of nephrotoxic medications, were found to increase the risk of AKI, independently of the combined antibiotics used.

Public awareness of online pharmacies, consumers' motivating factors, experience and satisfaction with online pharmacy services, and current barriers and motivators for non-consumers: The case of Saudi Arabia.

Purpose: Online pharmacies (OPs) represent a growing field that plays a major role in providing pharmaceutical services in Saudi Arabia (SA). Thus, investigating public awareness of this option and assessing consumers' experiences and satisfaction, as well as opportunities and barriers for OPs, were the main aims of this study. Participants and methods: In this cross-sectional study, adult participants (≥18 years) in SA completed a three-part, custom-designed online questionnaire. The first section collected information on participants' demographic characteristics, their awareness of the existence of OPs, and history of OP purchases. The second section explores customer satisfaction levels and motivating factors. Finally, the third section investigated non-consumers' reasons for not purchasing from OPs and sought information about services that could motivate them to make future purchase decisions. Results: In total, 487 participants completed the questionnaire; they were mostly female (65.7%) and younger than 40 years (57.1%). Among all the respondents, 89.3% were aware of the existence of OPs, and 60.2% purchased from OPs in the past. Most were satisfied with the product quality (92.7%), completeness of order delivery (91.2%), and condition of the product and packaging (89.3%). Furthermore, 99.2% of respondents indicated that they would continue to purchase from OPs. Customers' main motivational factors included saving time (85.5%), offers and discounts (83.6%), and variety of products (82.1%). Among non-consumers, the main reasons for not purchasing from OPs included a personal preference to visit a community pharmacy (87.2%), the ability to talk to pharmacists directly (83.6%), and the vicinity of a pharmacy (80.0%). Conclusions: These findings confirm the increasing level of awareness regarding the existence of OPs in SA. Overall, OP customers expressed satisfaction with the services provided. Nevertheless, various areas of improvement have emerged, such as improved delivery time and providing medical consultation services. Increasing public awareness of OP services provided is essential considering their significant role in reforming the healthcare system in SA.

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.

Adenosine response and failure to convert paroxysmal supraventricular tachycardia in the emergency department.

BACKGROUND AND IMPORTANCE: Although adenosine is the recommended first-line therapy for patients with paroxysmal supraventricular tachycardia (SVT), it may fail to restore normal sinus rhythm. The factors associated with this failure remain unclear. OBJECTIVE: To assess the response rate to adenosine and identify the factors causing adenosine failure in the management of paroxysmal SVT. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study was conducted on adult patients diagnosed with paroxysmal SVT and treated with adenosine in the emergency departments of two large tertiary hospitals between June 2015 and June 2021. OUTCOME MEASURE AND ANALYSIS: The primary outcome of the study was the patient response to adenosine, defined as the restoration of sinus rhythm documented in the patients' files. Backward-stepwise multivariate logistic regression was used to examine the predictors of adenosine failure based on the overall response to adenosine therapy. MAIN RESULTS: A total of 404 patients, with a mean age of 49 (SD 15) years and a BMI of 32 (SD 8) kg/m 2 , and treated with adenosine for paroxysmal SVT, were included. Sixty-nine percent of patients were women. The overall response rate to any adenosine dose was 86% (n = 347). The baseline heart rate did not significantly differ between adenosine responders and non-responders (179.6 ±â€…23.1 vs. 183.2 ±â€…23.4). An association was observed between the history of paroxysmal SVT and successful response to adenosine (odds ratio = 2.08; 95% confidence interval 1.05-4.11). CONCLUSION: The findings of this retrospective study suggested that the use of adenosine restored normal sinus rhythm in 86% of patients with paroxysmal SVT. Furthermore, a history of paroxysmal SVT and older age were associated with an increased chance of adenosine success.

Local causes of essential medicines shortages from the perspective of supply chain professionals in Saudi Arabia.

Background: The global supply chains of essential medicines faced frequent disruptions over the past five years, particularly during the COVID-19 pandemic. Different causes of prescription drug supply interruptions have been identified in Saudi Arabia. However, studies have yet to explore the views of pharmaceutical supply chain personnel regarding the causes of these interruptions. Therefore, this study aimed to survey individuals working in the pharmaceutical supply chains about their views on the observed interruptions in the supply of some essential drugs. Methods: This was a questionnaire-based cross-sectional study. The 10-item questionnaire was created based on the findings of previously published research that investigated the root causes of essential drug shortages and the impact of COVID-19 pandemic on the supply chains of essential drugs in Saudi Arabia. Purposive sampling was used to identify individuals with at least one year of experience in the area of the pharmaceutical supply chain, and the data collection occurred between April 19th, 2022 and October 23rd, 2022. In addition, descriptive statistics (e.g., frequencies and percentages) were conducted to present the views of the respondents. Results: Seventy-nine pharmaceutical supply chain specialists accepted the invitation and completed the questionnaire. About two-thirds (69.62%) of the respondents reported that centralized pharmaceutical procurement negatively affected the supply chain of essential drugs. Procurement of unregistered medications by the Saudi Food and Drug Authority (SFDA), as well as generic drugs with a history of recalls, and failure to supply requested quantities were the three most commonly reported reasons behind the observed interruptions in the supply of some essential drugs according to those respondents with a negative view of the centralized procurement. Furthermore, failure of pharmaceutical companies to inform SFDA of potential drug shortages, manufacturing issues, poor demand forecasting, unpredictable increase in demand, and low prices of essential drugs were also believed to be behind the observed interruptions in the supply of some essential medicines. Conclusion: The majority of surveyed pharmaceutical supply chain professionals held negative views about the role of centralized pharmaceutical procurement in exacerbating the issues with essential medicines supply chain. Future research should examine different strategies to improve purchasing and procurement practices in Saudi Arabia.

Comprehensive evaluation of six interventions for hospitalized patients with COVID-19: A propensity score matching study.

Purpose: The purpose of this study was to evaluate the effectiveness of either hydroxychloroquine, triple combination therapy (TCT), favipiravir, dexamethasone, remdesivir, or COVID-19 convalescent plasma (CCP) in comparison with standard-of-care for hospitalized patients with COVID-19 using real-world data from Saudi Arabia. Patients and methods: A secondary database analysis was conducted using the Saudi Ministry of Health database for patients with COVID-19. Adult (≥18 years) hospitalized patients with COVID-19 between March 2020 and January 2021 were included in the analysis. A propensity score matching technique was used to establish comparable groups for each therapeutic approach. Lastly, an independent t-test and chi-square test were used to compare the matching groups in the aspects of the duration of hospitalization, length of stay (LOS) in intensive care units (ICU), in-hospital mortality, and composite poor outcome. Multilevel logistic regression model was used to assess the association between the severity stage of COVID-19 and the outcomes while using the medication or intervention used as a grouping variable in the model. Results: The mean duration of hospitalization was significantly longer for patients who received TCT, favipiravir, dexamethasone, or CCP compared to patients who did not receive these therapies, with a mean difference ranging between 2.2 and 4.9 days for dexamethasone and CCP, respectively. Furthermore, the use of favipiravir or CCP was associated with a longer stay in ICU. Remdesivir was the only agent associated with in-hospital mortality benefit. A higher risk of mortality and poorer composite outcome were associated with the use of favipiravir or dexamethasone. However, the logistic regression model reveled that the difference between the two matched cohorts was due to the severity stage not the medication. Additionally, the use of hydroxychloroquine, TCT, or CCP had no impact on the incidence of in-hospital mortality or composite poor outcomes. Conclusion: Remdesivir was the only agent associated with in-hospital mortality benefit. The observed worsened treatment outcomes associated with the use of dexamethasone or FPV shall be attributed to the severity stage rather than the medication use. In light of these varied results, additional studies are needed to continue evaluating the actual benefits of these therapies.

Real-World Evaluation of the Safety and Effectiveness of Apixaban & Rivaroxaban Lead-in Dosing Compared to Parenteral Lead-in Dosing in the Treatment of Venous Thromboembolism: A Multi-Center Retrospective Cohort Study.

Background: Although parenteral anticoagulation lead-in is not recommended with apixaban and rivaroxaban, parenteral anticoagulation is often used to replace apixaban or rivaroxaban lead-in doses for the initial phase treatment of VTE. Thus, our study compares the safety and effectiveness of lead-in parenteral anticoagulation to lead-in apixaban or rivaroxaban in patients who received apixaban or rivaroxaban for VTE treatment. Methods: A multi-center retrospective cohort study included adult patients (aged ≥ 18 years) admitted to the hospital with acute VTE and treated with either apixaban or rivaroxaban. Patients were grouped depending on the lead-in anticoagulation received for initial VTE treatment into the "Direct oral anticoagulation (DOAC) lead-in" group if patients received an appropriate lead-in dose of apixaban and rivaroxaban and patients who received parenteral lead-in the "parenteral lead-in" group. Results: A total of 389 patients were included; the DOAC lead-in group included 296 patients, whereas 93 patients were in the parenteral lead-in group. VTE recurrence (rVTE) during hospitalization and within 30 days was numerically higher in the parenteral lead-in group compared to the DOAC lead-in group (3.3% vs 0.6%; p=0.09 and 1.1% vs 0.7%; p=0.560), with a significantly higher number of patients with rVTE at 90 days (5.4% vs 1.4%; p=0.039). However, none of the patient's characteristics were significantly associated with the incidence of rVTE. In addition, the major bleeding rate during hospitalization was significantly higher among the parenteral lead-in group than in the DOAC lead-in group (14.0% vs 3.7%; p<0.001). Conclusion: Parenteral anticoagulation lead-in before starting maintenance of apixaban and rivaroxaban showed a significantly higher risk of bleeding and a trend toward higher VTE recurrence than the DOAC lead-in. This study adds to the evidence supporting the utilization of the DOAC lead-in regimen in treating patients with VTE. Still, larger studies with robust designs are needed to confirm these findings.

Exploring the opportunities and challenges to implementing interprofessional education in Saudi Arabia: a qualitative study among faculty.

Interprofessional education (IPE) has potential benefits for improving the quality of patient care, but its implementation is challenged with multiple barriers. The primary objectives of this study were to explore the challenges, benefits, and incentives to establishing IPE from the perspective of healthcare faculty at King Saud University. Forty-five faculty members attended six focus groups, each consisting of 6-8 faculty members representing the five colleges. The focus group interview guide included the benefits of and barriers to establishing IPE in this academic institution, curricular design, and the feasibility of support from the colleges and University administration. A SWOC (Strengths, Weaknesses, Opportunities, Challenges) frame work was utilized to guide the focus group discussions, and the data were analyzed inductively using thematic analysis. Three main themes emerged and were related to (i) barriers, (ii) benefits, (iii) opportunities to facilitate the introduction of IPE, and (iv) suggestions on how to implement IPE and overcome challenges to establish an IPE curriculum. Participants were generally supportive of IPE and aware of the constraints that might impede its implementation. Moreover, they identified potential barriers and incentives to promote IPE. Although participants appreciated the long-term benefits of IPE, creating a supportive environment will require the involvement of the academic community, including students, faculty members, and the University's top management.

Comparative effectiveness of glucagon-like peptide-1 receptor agonists for the management of obesity in adults without diabetes: A network meta-analysis of randomized clinical trials.

Tirzepatide is a new glucagon-like peptide-1 receptor agonist (GLP-1RA) that has shown promising results for weight loss. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of GLP-1RAs for obesity management. Embase and MEDLINE were searched looking for randomized clinical trials (RCTs) that evaluated the efficacy of GLP-1RAs for weight loss in patients without diabetes. The main efficacy outcomes evaluated were the mean change in actual and percentage weight loss and the proportion of patients with weight loss of ≥5%-20%. Main safety outcomes evaluated include nausea, vomiting, diarrhea, constipation, loss of appetite, pancreatitis, gallbladder-related disorders, and withdrawal due to adverse events. Seven RCTs with more than 12,300 patients were analyzed, including patients with body mass index (BMI) ≥ 30 kg/m2 , or BMI ≥ 27 kg/m2 with comorbidities. Weekly tirzepatide 10 and 15 mg resulted in more weight loss than weekly semaglutide 2.4 mg, daily semaglutide 0.4 mg, or liraglutide 3 mg. Tirzepatide and weekly semaglutide demonstrated comparable results but with significantly higher odds of achieving ≥5%-20% weight loss compared with liraglutide. GLP-1RAs triggered more gastrointestinal adverse events than placebo, with no in-between difference. Although all GLP-1RAs lead to significant weight reduction, tirzepatide was associated with better efficacy outcomes while having a comparable safety profile.

The prescribing pattern of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in patient with type two diabetes mellitus: A two-center retrospective cross-sectional study.

Background: The use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with type 2 diabetes mellitus (T2DM) remains limited, especially in those with other compelling indications. Thus, this study aimed to describe the prescribing patterns of GLP-1-RA and SGLT2i in patients with T2DM and to determine the factors that affect the prescribing of these medications. Methods: This multicenter retrospective cross-sectional study reviewed the electronic health records of adult patients diagnosed with T2DM who received care between January and December 2020. The patients were classified according to their compelling indications into "patients who are more likely" to benefit from SGLT2i or GLP-1 RA and "patients who are less likely" to benefit from them. They were then further categorized depending on whether these medications were prescribed. Results: A total of 1,220 patients were included; most were female (56.9%). SGLT2i or GLP-1 RA were preferably prescribed in only 19% of the patients for reasons including BMI ≥ 27 kg/m2 (85.6%), uncontrolled T2DM (68.5%), high risk for ASCVD (23.9%), or established ASCVD (14%). The remaining 81.0% were underprescribed these agents. Patients at an older age or with a history of stroke or transient ischemic attack had higher odds of being underprescribed (OR 1.02; 95% CI: 1.01-1.03 and OR 2.86; 95% CI: 1.33-6.15), respectively. Conclusion: The results concur with those of previous studies highlighting the underutilization of GLP-1 RA and SGLT2i in patients with T2DM but also with compelling indications. To optimize the use of GLP-1 RA and SGLT2i for their additional benefits, prescribers need to assess the benefits of using these agents in patients who would likely benefit from them, regardless of DM control.