Effectiveness and safety of edoxaban versus warfarin in patients with nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular heartbeat. We evaluated the efficacy and safety of edoxaban versus warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies.Methods: In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR).Results: Patients treated with edoxaban had a significantly lower risk of ischemic stroke [hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.61–0.70; p < 0.0001] and major bleeding (HR = 0.58; 95% CI = 0.49–0.69; p < 0.0001) than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61–0.70; p < 0.0001 and HR = 0.58; 95% CI = 0.49–0.69; p < 0.0001, respectively.Conclusion: Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke

Dissemination of multiple carbapenem-resistant clones of Acinetobacter baumannii in the Eastern District of Saudi Arabia

It has previously been shown that carbapenem-resistant Acinetobacter baumannii are frequently detected in Saudi Arabia. The present study aimed to identify the epidemiology and distribution of antibiotic resistance determinants in these bacteria. A total of 83 A. baumannii isolates were typed by pulsed-field gel electrophoresis (PFGE), and screened by PCR for carbapenemase genes and insertion sequences. Antibiotic sensitivity to imipenem, meropenem, tigecycline, and colistin were determined. Eight different PFGE groups were identified, and were spread across multiple hospitals. Many of the PFGE groups contained isolates belonging to World-wide clone 2. Carbapenem resistance or intermediate resistance was detected in 69% of isolates. The blaVIM gene was detected in 94% of isolates, while blaOXA–23–like genes were detected in 58%. The data demonstrate the co-existence and wide distribution of a number of clones of carbapenem-resistant A. baumannii carrying multiple carbapenem-resistance determinants within hospitals in the Eastern Region of Saudi Arabia

Current Status and Future Direction of Hepatic Radioembolisation.

Radioembolisation is a locoregional treatment modality for hepatic malignancies. It consists of several stages that are vital to its success, which include a pre-treatment angiographic simulation followed by nuclear medicine imaging, treatment activity choice, treatment procedure and post-treatment imaging. All these stages have seen much advancement over the past decade. Here we aim to provide an overview of the practice of radioembolisation, discuss the limitations of currently applied methods and explore promising developments

Ethionamide Population Pharmacokinetic Model and Target Attainment in Multidrug-Resistant Tuberculosis

Ethionamide (ETA), an isonicotinic acid derivative, is part of the multidrug-resistant tuberculosis (MDR-TB) regimen. The current guidelines have deprioritized ETA because it is potentially less effective than other agents. Our aim was to develop a population pharmacokinetic (PK) model and simulate ETA dosing regimens in order to assess target attainment. This study included subjects from four different sites, including healthy volunteers and patients with MDR-TB. The TB centers included were two in the United States and one in Bangladesh. Patients who received ETA and had at least one drug concentration reported were included. The population PK model was developed, regimens with a total of 1,000 to 2,250 mg daily were simulated, and target attainment using published MICs and targets of 1.0-log kill and resistance suppression was assessed with the Pmetrics R package. We included 1,167 ethionamide concentrations from 94 subjects. The final population model was a one-compartment model with first-order elimination and absorption with a lag time. The mean (standard deviation [SD]) final population parameter estimates were as follows: absorption rate constant, 1.02 (1.11) h(-1); elimination rate constant, 0.69 (0.46) h(-1); volume of distribution, 104.16 (59.87) liters; lag time, 0.43 (0.32) h. A total daily dose of 1,500 mg or more was needed for >= 90% attainment of the 1.0-log kill target at a MIC of 1 mg/liter, and 2,250 mg/day led to 80% attainment of the resistance suppression target at a MIC of 0.5 mg/liter. In conclusion, we developed a population PK model and assessed target attainment for different ETA regimens. Patients may not be able to tolerate the doses needed to achieve the pre-defined targets supporting the current recommendations for ETA deprioritization

Prophylactic Medication during Radioembolization in Metastatic Liver Disease: Is It Really Necessary? A Retrospective Cohort Study and Systematic Review of the Literature

PURPOSE: Trans-arterial radioembolization is a well-studied tumoricidal treatment for liver malignancies; however, consensus and evidence regarding periprocedural prophylactic medication (PPM) are lacking. METHODS: A single-center retrospective analysis from 2014 to 2020 was performed in patients treated with 90Y-glass microspheres for neuroendocrine or colorectal liver metastases. Inclusion criteria were the availability of at least 3 months of clinical, biochemical, and imaging follow-up and post-treatment 90Y-PET/CT imaging for the determination of the whole non-tumorous liver absorbed dose (D h). Logistic regression models were used to investigate if variables (among which are P/UDCA and D h) were associated with either clinical toxicity, biochemical toxicity, or hepatotoxicity. Additionally, a structured literature search was performed in November 2022 to identify all publications related to PPM use in radioembolization treatments. RESULTS: Fifty-one patients received P/UDCA as post-treatment medication, while 19 did not. No correlation was found between toxicity and P/UDCA use. D h was associated with biochemical toxicity ( p = 0.05). A literature review resulted in eight relevant articles, including a total of 534 patients, in which no consistent advice regarding PPM was provided. CONCLUSION: In this single-center, retrospective review, P/UDCA use did not reduce liver toxicity in patients with metastatic liver disease. The whole non-tumorous liver-absorbed dose was the only significant factor for hepatotoxicity. No standardized international guidelines or supporting evidence exist for PPM in radioembolization

The Efficacy of Coil Embolization to Obtain Intrahepatic Redistribution in Radioembolization: Qualitative and Quantitative Analyses

Purpose: To evaluate the efficacy of coil embolization to obtain intrahepatic redistribution in patients undergoing radioembolization. Materials and Method: All patients treated with radioembolization at our institute were retrospectively analyzed, and all cases in which a tumor-feeding vessel was coil-embolized were selected. Two nuclear medicine physicians visually assessed the effect of redistribution. Furthermore, the redistribution of microspheres was measured by quantifying the activity distributed to the coil-embolized (dependent) segment relative to the other (non-dependent) segments and to the tumor(s) in that segment. Quantitative analysis was performed on post-treatment 90Y-PET and 166Ho-SPECT using Simplicit90Y software. Lesion response was measured according to RECIST 1.1 criteria at 3 months post-treatment. Results: Out of 37 cases, 32 were suitable for quantitative analysis and 37 for qualitative analysis. In the qualitative analysis, redistribution was deemed successful in 69% of cases. The quantitative analysis showed that the median ratio of the activity to the dependent embolized segments and the non-dependent segments was 0.88 (range 0.26–2.05) and 0.80 (range 0.19–1.62) for tumors in dependent segments compared with tumors in non-dependent segments. Using a cutoff ratio of 0.7 (30% lower activity concentration in comparison with the rest of the liver), 57% of cases were successful. At 3 months post-treatment, 6% of dependent tumors had partial response, 20% progressive disease, and 74% stable disease. In non-dependent tumors, this was, respectively, 16%, 20%, and 64%. Conclusion: Coil embolization of hepatic arteries to induce redistribution of microspheres has a limited success rate. Qualitative assessment tends to overrate redistribution

The Saudi Critical Care Society practice guidelines on the management of COVID-19 in the ICU: Therapy section

BACKGROUND: The rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU). METHODS: The SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations. RESULTS: The SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. CONCLUSION: The SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available

Carbon Dioxide Adsorption by a High-Surface-Area Activated Charcoal

An activated carbon (AC) with a high surface area of 4320.7 m2/g was synthesized via the chemical and thermal processing of walnut residues. The resulting activated charcoal was characterized by various techniques, including Brunauer–Emmett–Teller (BET) surface area analysis, scanning electron microscopy (SEM), and IR spectroscopy. The prepared activated carbon was studied for its capacity to adsorb CO2 gas. When exposed to CO2 for 60 min in a closed chamber at atmospheric pressure at 25 °C, the adsorption of a notable 301.1 mmol CO2 (13.25 g CO2) per gram of activated carbon was observed

Inductive Experimental Study of Corrosion Products of Medium Carbon Steel CK45 Hardened by Magnetized Water

This paper concerns the inductive experimental study of corrosion products of the medium carbon steel CK45DIN using magnetized water as hardening media, where the water has been exposed to a magnetic field of 1000 Gauss and 2000 Gauss, respectively, for time durations of 1 to 5 hours, with a volumetric flow rate of 4 gal/min. Medium carbon steel CK45DIN samples were exposed to air as corrosive environment for reasonable time interval, and the corrosion product was weighed in order to determine the loss of weight. The results showed that the corrosion rate of all samples decreased as the experiment progresses over time. Corrosion resistance of the medium carbon steel CK45DIN increased when we raised its temperature to 870°C for 40 minutes and hardened by magnetized water applied in a magnetic field with a strength of 1000 Gauss for 3 hours as compared with the sample hardened by normal water

Inhibition of cytochrome P450 enzymes by thymoquinone in human liver microsomes

The aim of the present study was to investigate the potential effect of thymoquinone (TQ) on the metabolic activity of four major drug metabolizing enzymes in human liver microsomes, namely cytochrome P450 (CYP) 1A2, CYP2C9, CYP2D6 and CYP3A4. The inhibition of CYP enzymatic activities by TQ was evaluated by incubating typical substrates (phenacetin for CYP1A2, tolbutamide for CYP2C9, dextromethorphan for CYP2D6, and testosterone for CYP3A4) with human liver microsomes and NADPH in the absence or presence of TQ (1, 10 and 100 µM). The respective metabolite of the substrate that was formed was measured by HPLC. Results of the presented study presented that the metabolic activities of all the investigated CYP enzymes, viz. CYP1A2, CYP2C9, CYP2D6 and CYP3A4, were inhibited by TQ. At 1 µM TQ, CYP2C9 enzyme activity was maximally inhibited by 46.35%, followed by CYP2D6 (20.26%) > CYP1A2 (13.52%) > CYP3A4 (12.82%). However, at 10 µM TQ, CYP2C9 enzyme activity was maximally inhibited by 69.69%, followed by CYP3A4 (23.59%) > CYP1A2 (23.51%) > CYP2D6 (11.42%). At 100 µM TQ, CYP1A2 enzyme activity was maximally inhibited by 81.92%, followed by CYP3A4 (79.24%) > CYP2C9 (69.22%) > CYP2D6 (28.18%). The IC50 (mean ± SE) values for CYP1A2, CYP2C9, CYP2D6 and CYP3A4 inhibition were 26.5 ± 2.9 µM, 0.5 ± 0.4 µM, >500 µM and 25.2 ± 3.1 µM, respectively. These findings suggest that there is a high probability of drug interactions resulting from the co-administration of TQ or herbs containing TQ with drugs that are metabolized by the CYP enzymes, particularly CYP2C9. Keywords: Thymoquinone, Cytochrome P450, Metabolism, Human liver microsome