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.

Evaluation of factors affecting pharmacists and pharmacy technicians' satisfaction towards practicing CE activities in Saudi Arabia.

Background: Continuing education (CE) is an essential requirement for pharmacy professionals to stay abreast with the evolving knowledge and skills of the practice and meet the regulatory mandate. The purpose of this research is to assess factors affecting the satisfaction of pharmacists and pharmacy technicians towards CE practices in Saudi Arabia. Material and methods: A self-administered survey instrument was developed following an extensive literature search. The questionnaire consisted of three sections: participants' demographics, data on CE activities over the past year and overall satisfaction, and statements of barriers (14 items) and facilitators (12 items) for participation in CE activities (scored on a 5-point Likert scale (5 = always, 1 = never)). The survey was piloted and then distributed as a link through the Saudi Commission for Health Specialties and Saudi Pharmaceutical Society (SPS) between Jan 2018 and Feb 2019. Results: Data was available on 398 pharmacists and 40 pharmacy technicians (completion rate was 55 %). The majority were practitioners, male, working in a hospital setting and had more than five years of practice experience. Half of the participants were from the Central Region and about one-third were non-Saudi. Only a quarter of the participants were satisfied/very satisfied with the current CE practices in Saudi Arabia. Job constraints (62.7 %), cost (55.9 %), schedule of CE activities (55.4 %), lack of information on CE opportunities (53 %) and professional burnout (49.7 %) were the top barriers. There was a significant level of dissatisfaction among pharmacy technicians when compared to pharmacists (p = 0.003), as well as among Saudi pharmacists when compared to non-Saudi pharmacists (p = 0.002). Lack of relevant CE activities (p = 0.05), lack of quality activities (p = 0.002), lack of recognition (p = 0.013) and lack of internet access (p = 0.006) were significantly more barriers for pharmacy technicians compared to pharmacists. The most identified facilitators to engage in CE activities were a personal desire to learn (78.4 %), the requirement to maintain a professional license (73.8 %) and relaxation provided by learning (58.5 %) and networking opportunities (53.4 %). The majority of the participants preferred conferences or interactive workshops, short CE over half a day or less, and the topic of disease management/drug therapy. Conclusion: The findings of the study highlight the need for a partnership strategy that includes various stakeholders to improve CE program quality and accessibility that supports and promotes the professional development of pharmacists and pharmacy technicians in Saudi Arabia. It also underscores the importance of meeting the preferences of pharmacy practitioners when designing CE programs and aligning such activities with their practices.

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

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

Evaluation of Apixaban standard dosing in underweight patients with non-valvular atrial fibrillation: a retrospective cohort study.

BACKGROUND: Recent guidelines recommend using direct oral anticoagulants (DOACs) as first-line agents in patients with non-valvular atrial fibrillation (NVAF). Research is currently investigating the use of Apixaban in underweight patients, with some results suggesting altered pharmacokinetics, decreased drug absorption, and potential overdosing in this population. This study examined the effectiveness and safety of standard Apixaban dosing in adult patients with atrial NVAF weighing less than 50 kg. METHODS: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC); adult patients with a body mass index (BMI) below 25 who received a standard dose of Apixaban (5 mg twice daily) were categorized into two sub-cohorts based on their weight at the time of Apixaban initiation. Underweight was defined as patients weighing ≤ 50 kg, while the control group (Normal weight) comprised patients weighing > 50 kg. We followed the patients for at least one year after Apixaban initiation. The study's primary outcome was the incidence of stroke events, while secondary outcomes included bleeding (major or minor), thrombosis, and venous thromboembolism (VTE). Propensity score (PS) matching with a 1:1 ratio was used based on predefined criteria and regression model was utilized as appropriate. RESULTS: A total of 1,433 patients were screened; of those, 277 were included according to the eligibility criteria. The incidence of stroke events was lower in the underweight than in the normal weight group at crude analysis (0% vs. 9.1%) p-value = 0.06), as well in regression analysis (OR (95%CI): 0.08 (0.001, 0.76), p-value = 0.002). On the other hand, there were no statistically significant differences between the two groups in the odds of major and minor bleeding (OR (95%CI): 0.39 (0.07, 2.03), p-value = 0.26 and OR (95%CI): 1.27 (0.56, 2.84), p-value = 0.40, respectively). CONCLUSION: This exploratory study revealed that underweight patients with NVAF who received standard doses of Apixaban had fewer stroke events compared to normal-weight patients, without statistically significant differences in bleeding events. To confirm these findings, further randomized controlled trials with larger sample sizes and longer observation durations are required.

Hospitalization Endpoint in Clinical Trials of Outpatient Settings: using Anti-SARS-COV-2 Therapy as an Example.

Purpose: In response to the COVID-19 pandemic, the World Health Organization (WHO) developed a set of outcome measures for trials primarily aimed at hospitalised patients. However, a gap exists in defining outcome standards for non-hospitalised patients. Therefore, this study aims to discuss hospitalisation as a primary outcome in outpatient trials and its potential pitfalls, specifically focusing on trials related to anti-SARS-COV-2 therapy. Methods: In this narrative review, researchers thoroughly searched MEDLINE and ClinicalTrials.gov from January 2020 to December 2022, targeting Phase III randomized controlled trials involving outpatients with mild-to-moderate COVID-19. The trials were specifically related to anti-SARS-COV-2 monoclonal antibodies or antiviral agents. The study collected essential data, including the type of intervention, comparator, primary objective, primary endpoint, and the use of estimands in the trial. Results: The search identified 12 trials that evaluated the efficacy of anti-SARS COV-2 therapies in a predefined population. Three studies used hospitalisation and death as primary endpoints in high-risk patients receiving monoclonal antibodies. Nine studies assessed the efficacy of several antiviral agents: four trials used hospitalisation and death as the main endpoints, while others used different measures such as virologic measures using the Reverse Transcription-Polymerase Chain Reaction test (RT-PCR), the eight-point WHO ordinal scale, symptom alleviation by Day 7 and time to clinical response. Conclusion: Choosing hospitalization as an endpoint may provide meaningful data such as the cost-effectiveness ratio of a drug. However, different hospital utilisation patterns and investigator decisions could bias clinical outcomes if no specific criteria are considered. Therefore, investigators should have clear criteria for determining variables that influence this measure.

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.

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 Impact of the COVID-19 Pandemic on Diabetes Self-Management in Saudi Arabia.

The COVID-19 pandemic disrupted healthcare worldwide, potentially impacting disease management. The objective of this study was to assess the self-management behaviors of Saudi patients with diabetes during and after the COVID pandemic period using the Arabic version of the Diabetes Self-Management Questionnaire (DSMQ). A cross-sectional study was conducted in patients aged ≥18 years diagnosed with type 2 diabetes mellitus who had at least one ambulatory clinic visit in each of the specified time frames (Pre-COVID-19: 1 January 2019-21 March 2020; COVID-19 Time frame: 22 March 2020 to 30 April 2021) utilizing the DSMQ questionnaire, with an additional three questions specifically related to their diabetes care during the COVID pandemic. A total of 341 patients participated in the study. The study results revealed that the surveyed patients showed moderately high self-care activities post-COVID-19. Total DSMQ scores were significantly higher in patients aged >60 years versus younger groups (p < 0.05). Scores were significantly lower in patients diagnosed for 1-5 years versus longer durations (p < 0.05). Patients on insulin had higher glucose management sub-scores than oral medication users (p < 0.05). Overall, DSMQ scores were higher than the pre-pandemic Saudi population and Turkish post-pandemic findings. DSMQ results suggest that, while COVID-19 negatively impacted some self-management domains, the Saudi patients surveyed in this study upheld relatively good diabetes control during the pandemic. Further research is warranted on specific barriers to optimize diabetes care during public health crises.

Are drug safety measures harmonized? A real-world evidence from three regulatory authorities.

Background: Risk minimization measures (RMMs) are interventions intended to mitigate or prevent the occurrence of adverse reactions associated with medications. Having consistent measures across regulatory bodies (i.e., the Saudi Food and Drug Authority (SFDA), the United States Food and Drug Administration (US FDA), and the European Medicines Agency (EMA)) benefits medication use and safety and ultimately the patient. Objectives: This study aimed to investigate whether there is variability in these published RMMs between the three regulatory bodies. Methods: A specific data collection form was created to extract information from the SFDA's RMM list, US FDA's Risk Evaluation and Mitigation Strategy (REMS) list, and EMA's Risk Management Plan (RMP) list, as of February 2022 all RMMs that were available on the websites were reviewed. Medications with the same trade name were matched across regulators, and unmatched medications were checked for approval status. For medication groups such as NSAIDs in the SFDA's RMM list, they were matched by searching for the groups individually in the regulatory websites. All risks and types of minimizing measures were compared. Results: A total of 317 medications were retrieved from the SFDA's RMM list. The majority of medication classes were immunosuppressants (n = 60), antihypertensive (n = 33), and oncology medication (n = 29). There were only 62 medications with REMS from the US FDA website, a total of 14 medications were approved by the SFDA, and only nine medications were matched with the SFDA's RMM list. Also, there were 828 medications with RMP from the EMA website, a total of 334 has RMM, 128 are approved by the SFDA, and 71 matched with the SFDA's RMM list. Furthermore, seven medications were matched between SFDA, US FDA and EMA. After content review, four medications had similar risks and measures across the regulators and three medications had different risks and measures across the regulators. For the medication groups, a total of 36 groups were in the SFDA's list, 18 groups were matched with the US FDA, and 14 were matched with the EMA. Conclusions: Our study showed substantial differences among the regulatory authorities regarding RMMs. Harmony in published risk measures can have a significant impact on medication safety.

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.

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.

The impact of a restricted pregabalin prescription policy on drug utilization: An observational multicenter study.

Background: The Saudi Food and Drug Authority (SFDA) classified pregabalin as a controlled substance in 2018; however, whether this policy change has affected pregabalin use is unclear. This study examined the trends in pregabalin prescriptions before and after the SFDA restriction. In addition, the co-prescription of controlled analgesics and the use of pregabalin for approved indications were also evaluated. Method: A cross-sectional study was conducted on outpatient pregabalin prescriptions from three healthcare centers in Saudi Arabia. Interrupted time series analysis was used to assess changes over time in pregabalin prescriptions and the number of patients receiving pregabalin. June 2016 to June 2017 was identified as the pre-restriction period, and July 2018 to July 2019 as the post-restriction period. Results: In this study, 77,760 pregabalin prescriptions were identified. There were 9,076 patients on pregabalin in the pre-restriction period with 16,875 prescriptions, compared with 7,123 patients and 19,484 prescriptions post-restriction. The total number of pregabalin users decreased by 21.5% post-restriction, and prescriptions increased by 15.5%. There was no significant change in the monthly trends in pregabalin prescriptions before and after the restriction. However, the of tramadol and acetaminophen/codeine prescriptions in patients who were using pregabalin increased in the post-restriction period by 21% and 16.1%, respectively. Conclusion: Pregabalin use was reduced after the SFDA-enforced prescription restriction was implemented. This was accompanied by increased narcotics use in the post-implementation phase.

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.

Potentially Inappropriate Medications Use among Older Adults with Dyslipidaemia.

BACKGROUND: Since older patients with dyslipidemia frequently receive many prescriptions, medication errors are typical and expected in this population. This risk has increased by using potentially inappropriate medications. The 2019 Beers criteria were used in this study to investigate potentially inappropriate medication use among older individuals with dyslipidemia. METHODS: A cross-sectional retrospective analysis used data from electronic medical records from an ambulatory-care environment. Patients with dyslipidemia who were older adults (>65 years old) were included. To describe and find potential determinants of potentially inappropriate medication usage, descriptive statistics and logistic regression were employed. RESULTS: This study included 2209 older adults (age ≥ 65) with dyslipidemia. The mean age was 72.1 ± 6.0 years, and the majority of the study sample had hypertension (83.7%) and diabetes (61.7%), and around 80.0% were using polypharmacy. The prevalence of potentially inappropriate medications to be avoided among older adults with dyslipidemia was 48.6%. A high risk of potentially inappropriate medication usage was found in older patients with dyslipidemia who had polypharmacy and comorbid diabetes, ischemic heart disease, and anxiety. CONCLUSIONS: This study showed that the number of medications prescribed and the presence of concurrent chronic health conditions are important indicators of the risk of potentially inappropriate medications in ambulatory older patients with dyslipidemia.

Incidence and Clinical Outcomes of New-Onset Atrial Fibrillation in Critically lll Patients with COVID-19: A Multicenter Cohort Study - New-Onset Atrial Fibrillation and COVID-19.

Atrial fibrillation (Afib) can contribute to a significant increase in mortality and morbidity in critically ill patients. Thus, our study aims to investigate the incidence and clinical outcomes associated with the new-onset Afib in critically ill patients with COVID-19. A multicenter, retrospective cohort study includes critically ill adult patients with COVID-19 admitted to the intensive care units (ICUs) from March, 2020 to July, 2021. Patients were categorized into two groups (new-onset Afib vs control). The primary outcome was the in-hospital mortality. Other outcomes were secondary, such as mechanical ventilation (MV) duration, 30-day mortality, ICU length of stay (LOS), hospital LOS, and complications during stay. After propensity score matching (3:1 ratio), 400 patients were included in the final analysis. Patients who developed new-onset Afib had higher odds of in-hospital mortality (OR 2.76; 95% CI: 1.49-5.11, P = .001). However, there was no significant differences in the 30-day mortality. The MV duration, ICU LOS, and hospital LOS were longer in patients who developed new-onset Afib (beta coefficient 0.52; 95% CI: 0.28-0.77; P < .0001,beta coefficient 0.29; 95% CI: 0.12-0.46; P < .001, and beta coefficient 0.35; 95% CI: 0.18-0.52; P < .0001; respectively). Moreover, the control group had significantly lower odds of major bleeding, liver injury, and respiratory failure that required MV. New-onset Afib is a common complication among critically ill patients with COVID-19 that might be associated with poor clinical outcomes; further studies are needed to confirm these findings.

The use of enoxaparin as venous thromboembolism prophylaxis in bariatric surgery: A retrospective cohort study.

Introduction: Venous thromboembolism (VTE) is one of the major causes of morbidity and mortality in bariatric patients. The use of low-molecular-weight heparin (LMWH), as enoxaparin, is considered one of the mainstays thromboprophylaxis regimens in postoperative bariatric patients. Despite the universal agreement on the importance of thromboprophylaxis in these patients, there are inadequate strong recommendations for its dosing and duration. The aim of our study is to explore the current practice on using enoxaparin in bariatric patients, as well as to assess both the efficacy and safety of varying dosing regimens. Material and methods: This is a retrospective cohort study of morbidly obese patients who underwent bariatric procedure at a tertiary care hospital between 2016 and 2019. All adult patients who met the eligibility criteria for bariatric surgery and received enoxaparin with a minimum follow-up period of one month were included in our study. Participants with a history of coagulopathy, renal or hepatic insufficiency were excluded from the study. Data collected include patient demographics, VTE risk factors, and co-morbidities. The outcome of treatment failure was defined as the composite of either VTE or major bleeding. Results: A total of 1,169 patients who underwent bariatric surgery were included in the study. The mean age was 35.54 years, with mean body mass index (BMI) of 45.78 kg/m2. The mean duration of enoxaparin use was 9 days, and the majority of patients (78%) received a prophylaxis dose of 40 mg subcutaneously (SC) once daily. The overall rate of VTE at 90 days was 1.4% while only 0.1% of patients developed major bleeding. There was no statistically significant difference in patients' age, gender, BMI, or various enoxaparin dosing regimens between patients who developed VTE or bleeding versus patients who did not develop. Patient's weight was the only statistically significant risk factor that directly correlated to higher risk of complications (P = 0.006). In the multivariable logistic regression model, higher BMI was significantly associated with treatment failure, either VTE or major bleeding [OR 1.05 (95% CI 1.0-1.09); P = 0.038]. Conclusions: The rate of VTE or major bleeding did not differ in patients who received various enoxaparin regimens. Patients undergoing bariatric surgery may benefit from enoxaparin thromboprophylaxis dose of 40 mg SC daily for a total duration of 14 days, with higher doses may be needed for extremely obese patients. We recommend standardizing the current practice of VTE prophylaxis post bariatric surgery and unifying the optimal dose and duration.

The impact of HMG-CoA reductase inhibitors use on the clinical outcomes in critically ill patients with COVID-19: A multicenter, cohort study.

Background: The cardiovascular complications of Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. HMG-CoA Reductase Inhibitors (statins) are known to have pleiotropic and anti-inflammatory effects and may have antiviral activity along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the impact of statin use on the clinical outcome of critically ill patients with COVID-19. Methods: A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 who were admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on the statin use during ICU stay and were matched with a propensity score based on patient's age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 day mortality, ventilator-free days (VFDs) at 30 days, and ICU complications were secondary endpoints. Results: A total of 1,049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality [hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004] and 30-day mortality [hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03] were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin therapy had lower odds of hospital-acquired pneumonia [OR 0.48 (95% CI 0.32, 0.69), P < 0.001], lower levels of inflammatory markers on follow-up, and no increased risk of liver injury. Conclusion: The use of statin therapy during ICU stay in critically ill patients with COVID-19 may have a beneficial role and survival benefit with a good safety profile.

Adherence to Prescribing Guideline-Directed Medical Therapy at Hospital Discharge in Subjects With Acute Coronary Syndrome, and the Relationship With Mortality.

Introduction The use of guideline-directed medical therapy (GDMT) after acute coronary syndrome (ACS) is associated with a significant reduction in mortality; however, suboptimal prescribing of these therapies has been reported. This study aims to determine adherence to prescribing GDMT in subjects with ACS at hospital discharge and to measure the relationship between this adherence and one-year mortality. Methods A retrospective cohort study was conducted on adults admitted with an ACS. The primary outcome was adherence to GDMT, defined as compliance with prescribing aspirin, angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs), beta-blockers, and high-intensity statins, according to international guideline recommendations. The secondary outcomes included identifying predictors for adherence to prescribing GDMT and one-year mortality. Descriptive statistics and logistic regression analyses were used. Results In 460 patients identified, the average age was 61.42 (±11.85) and the majority were male (76.09%). Adherence to prescribing GDMT was achieved in 70.87% of study subjects. The highest prescribing rates were associated with statins (95.22%) and the lowest with ACEIs/ARBs (81.09%). In the multivariable analysis, females and those diagnosed with unstable angina had fewer odds of receiving GDMT (odds ratio [OR]=0.48, 95% confidence interval [CI]=0.30-0.78), and (OR=0.42, CI=0.24-0.75), respectively, while a history of dyslipidemia was associated with higher odds of receiving GDMT. During the one-year follow-up, 23 subjects died in this study, and adherence to GDMT was associated with fewer deaths (OR=0.38, CI=0.16-0.93). Conclusions This study shows that there is a pressing need to develop effective strategies to improve compliance with prescribing lifesaving drugs for secondary prevention in subjects with ACS.

Genetics of ataxia telangiectasia in a highly consanguineous population.

Ataxia telangiectasia (AT) is a rare autosomal recessive multisystemic disorder. It usually presents in toddler years with progressive ataxia and oculomotor apraxia, or less commonly, in the late-first or early-second decade of life with mixed movement disorders. Biallelic mutations in ataxia telangiectasia mutated gene (ATM) cause AT phenotype, a disease not well documented in Saudi Arabia, a highly consanguineous society. We studied several Saudi AT patients, identified ATM variants, and investigated associated clinical features. We included 17 patients from 12 consanguineous families. All patients had comprehensive clinical and radiological assessment, and most were examined through whole-exome sequencing (WES). Selected individuals were analyzed using various genetic approaches. We identified five different ATM variants in our patients: three previously reported mutations, and two novel variants. Nearly all patients had classical AT presentation except for two patients with a milder phenotype. Among the three known variants, a deletion causing truncation (c.381delA resulting in p.(Val128Ter)) was identified in 13 patients. Two patients harboured the other two truncating variants, (c.9001_9002delAG resulting in p.Ser3001Phefs*6) and (c.9066delA resulting in p.Glu3023Alafs*10) and two patients had novel compound heterozygous variants (NM_000051.3:Paternal Allele:c.8762C > G;p.Thr2921Arg and Maternal Allele:c.1057T > C;p.Cys353Arg). We speculate that c.381delA is a founder mutation in our population. This study provides a genotype-phenotype relationship in a previously unstudied consanguineous population. Our findings contribute to improve local clinical care, therapy, and genetic counseling.

Interrupted versus uninterrupted anticoagulation therapy for catheter ablation in adults with arrhythmias.

BACKGROUND: The management of anticoagulation therapy around the time of catheter ablation (CA) procedure for adults with arrhythmia is critical and yet is variable in clinical practice. The ideal approach for safe and effective perioperative management should balance the risk of bleeding during uninterrupted anticoagulation while minimising the risk of thromboembolic events with interrupted therapy. OBJECTIVES: To compare the efficacy and harms of interrupted versus uninterrupted anticoagulation therapy for catheter ablation (CA) in adults with arrhythmias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and SCI-Expanded on the Web of Science for randomised controlled trials on 5 January 2021. We also searched three registers on 29 May 2021 to identify ongoing or unpublished trials. We performed backward and forward searches on reference lists of included trials and other systematic reviews and contacted experts in the field. We applied no restrictions on language or publication status. SELECTION CRITERIA: We included randomised controlled trials comparing uninterrupted anticoagulation with any modality of interruption with or without heparin bridging for CA in adults aged 18 years or older with arrhythmia. DATA COLLECTION AND ANALYSIS: Two review authors conducted independent screening, data extraction, and assessment of risk of bias. A third review author resolved disagreements. We extracted data on study population, interruption strategy, ablation procedure, thromboembolic events (stroke or systemic embolism), major and minor bleeding, asymptomatic thromboembolic events, cardiovascular and all-cause mortality, quality of life (QoL), length of hospital stay, cost, and source of funding. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: We identified 12 studies (4714 participants) that compared uninterrupted periprocedural anticoagulation with interrupted anticoagulation. Studies performed an interruption strategy by either a complete interruption (one study) or by a minimal interruption (11 studies), of which a single-dose skipped strategy was used (nine studies) or two-dose skipped strategy (two studies), with or without heparin bridging. Studies included participants with a mean age of 65 years or greater, with only two studies conducted in relatively younger individuals (mean age less than 60 years). Paroxysmal atrial fibrillation (AF) was the primary type of AF in all studies, and seven studies included other types of AF (persistent and long-standing persistent). Most participants had CHADS2 or CHADS2-VASc demonstrating a low-moderate risk of stroke, with almost all participants having normal or mildly reduced renal function. Ablation source using radiofrequency energy was the most common (seven studies). Ten studies (2835 participants) were conducted in East Asian countries (Japan, China, and South Korea), while the remaining two studies were conducted in the USA. Eight studies were conducted in a single centre. Postablation follow-up was variable among studies at less than 30 days (three studies), 30 days (six studies), and more than 30 days postablation (three studies). Overall, the meta-analysis showed high uncertainty of the effect between the interrupted strategy compared to uninterrupted strategy on the primary outcomes of thromboembolic events (risk ratio (RR) 1.76, 95% confidence interval (CI) 0.33 to 9.46; I2 = 59%; 6 studies, 3468 participants; very low-certainty evidence). However, subgroup analysis showed that uninterrupted vitamin A antagonist (VKA) is associated with a lower risk of thromboembolic events without increasing the risk of bleeding. There is also uncertainty on the outcome of major bleeding events (RR 1.10, 95% CI 0.59 to 2.05; I2 = 6%; 10 studies, 4584 participants; low-certainty evidence). The uncertainty was also evident for the secondary outcomes of minor bleeding (RR 1.01, 95% CI 0.46 to 2.22; I2 = 87%; 9 studies, 3843 participants; very low-certainty evidence), all-cause mortality (RR 0.34, 95% CI 0.01 to 8.21; 442 participants; low-certainty evidence) and asymptomatic thromboembolic events (RR 1.45, 95% CI 0.85 to 2.47; I2 = 56%; 6 studies, 1268 participants; very low-certainty evidence). There was a lower risk of the composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality) in the interrupted compared to uninterrupted arm (RR 0.23, 95% CI 0.07 to 0.81; 1 study, 442 participants; low-certainty evidence). In general, the low event rates, different comparator anticoagulants, and use of different ablation procedures may be the cause of imprecision and heterogeneity observed. AUTHORS' CONCLUSIONS: This meta-analysis showed that the evidence is uncertain to inform the decision to either interrupt or continue anticoagulation therapy around CA procedure in adults with arrhythmia on outcomes of thromboembolic events, major and minor bleeding, all-cause mortality, asymptomatic thromboembolic events, and a composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality).  Most studies in the review adopted a minimal interruption strategy which has the advantage of reducing the risk of bleeding while maintaining a lower level of anticoagulation to prevent periprocedural thromboembolism, hence low event rates on the primary outcomes of thromboembolism and bleeding. The one study that adopted a complete interruption of VKA showed that uninterrupted VKA reduces the risk of thromboembolism without increasing the risk of bleeding. Hence, future trials with larger samples, tailored to a more generalisable population and using homogeneous periprocedural anticoagulant therapy and ablation source are required to address the safety and efficacy of the optimal management of anticoagulant therapy prior to ablation.