Comparisons of effectiveness and safety between on-label dosing, off-label underdosing, and off-label overdosing in Asian and non-Asian atrial fibrillation patients treated with rivaroxaban: a systematic review and meta-analysis of observational studies.

AIMS: Limited real-world data show that rivaroxaban following dosage criteria from either ROCKET AF [20 mg/day or 15 mg/day if creatinine clearance (CrCl) < 50 mL/min] or J-ROCKET AF (15 mg/day or 10 mg/day if CrCl < 50 mL/min) is associated with comparable risks of thromboembolism and bleeding with each other in patients with non-valvular atrial fibrillation (NVAF). We are aimed to study whether these observations differ between Asian and non-Asian subjects. METHODS AND RESULTS: A systematic review and meta-analysis with random effects was conducted to estimate the aggregate hazard ratio (HR) and 95% confidence interval (CI) using PubMed and MEDLINE databases from 8 September 2011 to 31 December 2022 searched for adjusted observational studies that reported relevant clinical outcomes of NVAF patients receiving rivaroxaban 10 mg/day if CrCl > 50 mL/min, on-label dose rivaroxaban eligible for ROCKET AF or J-ROCKET AF, and rivaroxaban 20 mg/day if CrCl < 50 mL/min. Effectiveness and safety endpoints were compared between ROCKET AF and J-ROCKET AF dosing regimen in Asian and non-Asian subjects, separately. Also, risks of events of rivaroxaban 10 mg/day despite of CrCl > 50 mL/min and rivaroxaban 20 mg/day despite of CrCl < 50 mL/min were compared to that of 'ROCKET AF/J-ROCKET AF dosing'. Sensitivity analyses were performed by sequential elimination of each study from the pool. The meta-regression analysis was performed to explore the influence of potential factors on the effectiveness and safety outcomes. Eighteen studies involving 67 571 Asian and 54 882 non-Asian patients were included. Rivaroxaban following J-ROCKET AF criteria was associated with comparable risks of thromboembolism in the Asian subgroup, whereas rivaroxaban following J-ROCKET AF criteria was associated with higher risks of all-cause mortality (HR:1.30; 95% CI:1.05-1.60) compared with that of ROCKET AF criteria in the non-Asian population. There were no differences in risks of major bleeding between rivaroxaban following J-ROCKET AF vs. ROCKET AF criteria either in the Asian or non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism (HR:1.64; 95% CI:1.28-2.11) but lower risk of major bleeding (HR:0.72; 95% CI:0.57-0.90) compared with eligible dosage criteria. The use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse clinical outcomes in the risks of thromboembolism (HR:1.32; 95% CI:1.09-1.59), mortality (HR:1.33; 95% CI:1.10-1.59), and major bleeding (HR:1.26; 95% CI:1.03-1.53) compared with eligible dosage criteria. The pooled results were generally in line with the primary effectiveness and safety outcomes by removing a single study at one time. Meta-regression analyses failed to detect the bias in most potential patient characteristics associated with the clinical outcomes. CONCLUSION: Rivaroxaban dosing regimen following J-ROCKET criteria may serve as an alternative to ROCKET AF criteria for the Asian population with NVAF, whereas the dosing regimen following ROCKET AF criteria was more favourable for the non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism but a lower risk of major bleeding, while use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse outcome in most clinical events.

Comparative safety and effectiveness of non-vitamin K oral anticoagulants versus warfarin in patients with non-valvular atrial fibrillation: A network meta-analysis.

BACKGROUND: The introduction of non-vitamin K antagonist oral anticoagulants (NOACs), with a non-inferior or superior clinical efficacy profile compared to vitamin K antagonists (VKAs), has significantly improved the safety profile and treatment adherence of patients with non-valvular atrial fibrillation (AF). However, few studies have compared the effectiveness and safety of NOACs. Therefore, we conducted this systematic review and network meta-analysis to compare the safety and clinical effectiveness of NOACs and VKAs in patients with non-valvular AF. METHODS: An online bibliographic search was conducted to retrieve real-world evidence studies published between January 2019 and June 2022. RESULTS: Dabigatran was associated with lower risks of major bleeding, ischemic stroke, and intracranial hemorrhage than warfarin. Among the NOACs, only dabigatran had a lower risk of all-cause mortality than warfarin. Dabigatran was also associated with lower risks of major bleeding and intracranial hemorrhage than rivaroxaban. CONCLUSION: Our meta-analysis confirms that dabigatran's real-world safety and clinical effectiveness align with the results of pivotal clinical trials.

Erythrocyte degradation, metabolism, secretion, and communication with immune cells in the blood during sepsis: A review.

Sepsis is a health issue that affects millions of people worldwide. It was assumed that erythrocytes were affected by sepsis. However, in recent years, a number of studies have shown that erythrocytes affect sepsis as well. When a pathogen invades the human body, it infects the blood and organs, causing infection and sepsis-related symptoms. Pathogens change the internal environment, increasing the levels of reactive oxygen species, influencing erythrocyte morphology, and causing erythrocyte death, i.e., eryptosis. Characteristics of eryptosis include cell shrinkage, membrane blebbing, and surface exposure of phosphatidylserine (PS). Eryptotic erythrocytes increase immune cell proliferation, and through PS, attract macrophages that remove the infected erythrocytes. Erythrocyte-degraded hemoglobin derivatives and heme deteriorate infection; however, they could also be metabolized to a series of derivatives. The result that erythrocytes play an anti-infection role during sepsis provides new perspectives for treatment. This review focuses on erythrocytes during pathogenic infection and sepsis.

COVID-19 and the lungs: A review.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) attacks pulmonary alveolar cells via angiotensin-converting enzyme 2 (ACE2) receptors and causes pulmonary infections that result in coronavirus disease (COVID-19), inducing immune responses that can result in severe pneumonia. We reviewed the clinical experiences of lung diseases during the COVID-19 pandemic to offer insights into the adaptations made by experts in the diagnosis and treatment of these comorbidities. Various lung comorbidities increase the severity of COVID-19 and associated mortality by amplifying ACE2 expression. Additionally, the COVID-19 pandemic has changed the use of routine diagnostic pulmonary imaging methods, making chest sonography scoring the most convenient, as it can be conducted bedside. Treatment protocols for SARS-CoV-2 infection and the underlying lung diseases are also affected owing to potential interactions. The optimal diagnostic methods and treatment protocols for lung diseases have been adapted worldwide to increase survival rates and attenuate acute lung injuries during the COVID-19 pandemic.

Early Screening of Risk for Multidrug-Resistant Organisms in the Emergency Department in Patients With Pneumonia and Early Septic Shock: Single-Center, Retrospective Cohort Study.

OBJECTIVES: Pneumonia is the fourth leading cause of death globally, with rapid progression during sepsis. Multidrug-resistant organisms (MDROs) are becoming more common with some healthcare-associated pneumonia events. Early detection of MDRO risk improves the outcomes; however, MDROs risk in pneumonia with sepsis is unknown. This study investigated the disease outcomes of pneumonia with septic shock in patients admitted in the emergency department (ED) intensive care unit (ICU), a population with a high prevalence of MDROs, after early screening of MDROs risk. METHODS: In this retrospective cohort study, patients with pneumonia and early septic shock (n = 533) admitted to the ED at the Taipei Tzu Chi Hospital from 2013 to 2019 were selected. The study population was divided into four subgroups after the MDROs risk and screening procedure were completed within 1 or 6 h of admission. ICU mortality and multidrug antibiotic therapy were compared. RESULTS: The high-risk MDROs groups had higher percentage of P aeruginosa than the low-risk group. Furthermore, the appropriate ED first antibiotics were higher in the 1-h subgroup than in the 6-h subgroup of the high-risk MDROs group. In multivariate analysis, the 6-h high-risk MDROs group had an adjusted odds ratio of 7.191 (95% CI: 2.911-17.767, P < 0.001) and 2.917 (95% CI: 1.456-5.847, P = 0.003) for ICU mortality and multidrug therapy in the ICU, respectively, after adjusting for other confounding factors. CONCLUSIONS: MDRO screening within 1 h is recommended following admission of patients with pneumonia and early septic shock in the ED, especially in areas with a high prevalence of MDROs.

Junctionless Poly-GeSn Ferroelectric Thin-Film Transistors with Improved Reliability by Interface Engineering for Neuromorphic Computing.

Ferroelectric HfZrOx (Fe-HZO) with a larger remnant polarization (Pr) is achieved by using a poly-GeSn film as a channel material as compared with a poly-Ge film because of the lower thermal expansion that induces higher stress. Then two-stage interface engineering of junctionless poly-GeSn (Sn of ∼5.1%) ferroelectric thin-film transistors (Fe-TFTs) based on HZO was employed to improve the reliability characteristics. With stage I of NH3 plasma treatment on poly-GeSn and subsequent stage II of Ta2O5 interfacial layer growth, the interfacial quality between Fe-HZO and the poly-GeSn channel is greatly improved, which in turn enhances the reliability performance in terms of negligible Pr degradation up to 106 cycles (±2.7 MV/1 ms) and 96% Pr after a 10 year retention at 85 °C. Furthermore, to emulate the synapse plasticity of the human brain for neuromorphic computing, besides manifesting the capability of short-term plasticity, the devices also exhibit long-term plasticity with the characteristics of analog conductance (G) states of 80 levels (>6 bit), small linearity for potentiation and depression of -0.83 and 0.62, high symmetry, and moderate Gmax/Gmin of 9.6. By employing deep neural network, the neuromorphic system with poly-GeSn Fe-TFT synaptic devices achieves 91.4% pattern recognition accuracy. In addition, the learning algorithm of spike-timing-dependent plasticity based on spiking neural network is demonstrated as well. The results are promising for on-chip training, making it possible to implement neuromorphic computing by monolithic 3D ICs based on poly-GeSn Fe-TFTs.