Synthesis, characterization and antibacterial activity of cyclohexyltin N-(salicylidene)valinates

Abstract: Two new cyclohexyltin N-(salicylidene)valinates, [2-HOC6H4CH=NCH(CH(CH3)2)COO]SnCy3 (1) and [2-OC6H4CH=NCH(CH(CH3)2)COO]SnCy2 (2) (Cy = cyclohexyl), have been synthesized and characterized by elemental analysis, IR, and 1H NMR. The crystal structure of 2 has been determined by X-ray single crystal diffraction. In the complexes, the carboxylate is monodentate. Complex 1 is a four-coordinated tin compound, and 2 has a distorted trigonal bipyramidal geometry with the axial locations occupied by one carboxylate oxygen and a phenolic oxygen of the ligand. Bioassay results show that 1 and 2 have good in vitro antibacterial activity against Escherichia coli

ADVERSE EVENTS IN LOW VERSUS NORMAL BODY WEIGHT PATIENTS PRESCRIBED APIXABAN OR RIVAROXABAN FOR ATRIAL FIBRILLATION

Background: Clinical trials comparing direct oral anticoagulants (DOACs) to warfarin included only a small number of patients that weighed less than 60 kilograms (kg). The safety and efficacy of DOACs in low weight adult patients with atrial fibrillation (AF) is still unclear. Published data is not only sparse but have mixed outcomes. Therapy with DOACs may increase bleeding and/or clotting risk with uncertain antithrombotic benefit in low weight patients. Objective: To assess bleeding and thrombotic event rates for patients with AF that are prescribed a DOAC and have a low body weight (less than 60 kg) versus patients that have a normal body weight (60 to 100 kg). Methods: Within the Michigan Anticoagulation Quality Improvement Initiative (MAQI2), we analyzed data for patients with AF prescribed apixaban or rivaroxaban from 2017 through 2021 who had at least 12 months of follow-up. Patients were excluded if they were prescribed dosing different from package insert instructions. Patients were divided by weight into low (less than 60 kg) and normal (60 to 100 kg) cohorts. Assessments included rates of thrombotic events, major bleeding events (International Society on Thrombosis and Haemostasis [ISTH]), and non-major bleeding events requiring an Emergency Department (ED) visit. Patient characteristics were compared using Chi-square and t-test. Bleeding event rates were adjusted for age, gender, and diabetes mellitus and thrombotic event rates were adjusted by CHA2DS2-VASc score. Poisson regression was used to estimate adjusted adverse event rates to control for potentially confounding covariates (apixaban only due to few patients prescribed rivaroxaban). Results: A total of 616 patients met the inclusion criteria: 83 (13.5%) low weight and 533 (86.5%) normal weight. Most patients were prescribed apixaban (88.5%) with the low weight cohort more often prescribed the lower dose of apixaban (55% versus 6.2%, p\u3c0.0001). The low weight cohort had a higher mean age (78.9% versus 74.4%, p\u3c0.0002), proportion of females (94% versus 54%, p\u3c0.0001) and CHA2DS2-VASc score (4.4 (1.6) versus 3.9 (1.6)), but a lower proportion of patients with diabetes mellitus (9.6% versus 25.1%, p\u3c0.0018) [Table 1]. In the unadjusted analysis of patients prescribed apixaban, non-major bleeding events requiring an ED visit (10.8 per 100 patient-years versus 7.4 per 100 patient-years, p\u3c0.0001), occurred more often in the low versus normal weight patient cohort [Table 2]. However, adjusted analysis found no statistically significant difference in events in low and normal weight cohorts prescribed apixaban [Table 2]. Comparisons within patients prescribed rivaroxaban could not be made due to a small sample size of low weight patients. Conclusions: Among low weight patients with AF the use of apixaban was not associated with bleeding (major and non-major) or thrombotic events after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients

Comparison of Patient Outcomes Before and After Switching From Warfarin to a Direct Oral Anticoagulant Based on Time in Therapeutic Range Guideline Recommendations

This cohort study evaluates stroke and major bleeding rates before and after switching from warfarin to a direct oral anticoagulant (DOAC) in patients grouped by pre-switch time-in-therapeutic range guideline thresholds

An On-demand Photonic Ising Machine with Simplified Hamiltonian Calculation by Phase-encoding and Intensity Detection

Photonic Ising machine is a new paradigm of optical computing, which is based on the characteristics of light wave propagation, parallel processing and low loss transmission. Thus, the process of solving the combinatorial optimization problems can be accelerated through photonic/optoelectronic devices. In this work, we have proposed and demonstrated the so-called Phase-Encoding and Intensity Detection Ising Annealer (PEIDIA) to solve arbitrary Ising problems on demand. The PEIDIA is based on the simulated annealing algorithm and requires only one step of optical linear transformation with simplified Hamiltonian calculation. With PEIDIA, the Ising spins are encoded on the phase term of the optical field and only intensity detection is required during the solving process. As a proof of principle, several 20 and 30-dimensional Ising problems have been solved with high ground state probability

Length of Anticoagulation in Provoked Venous Thromboembolism: A Multicenter Study of How Real-World Practice Mirrors Guideline Recommendations

Background For more than a decade, guidelines have recommended a limited 3 months of anticoagulation for the treatment of provoked venous thromboembolism (VTE). How closely real-world practice follows guideline recommendations is not well described. Methods and Results In our multicenter, retrospective cohort study, we evaluated trends in anticoagulation duration for patients enrolled in the MAQI(2) (Michigan Anticoagulation Quality Improvement Initiative) registry who were receiving anticoagulation for a provoked VTE. The MAQI(2) registry comprises 6 centers in Michigan that manage patients\u27 long-term anticoagulation. We identified 474 patients on warfarin and 302 patients on direct oral anticoagulants who were receiving anticoagulation for a primary indication of provoked VTE between 2008 and 2020. Using a predefined threshold of 120 days (3 months plus a buffer period), predictors of extended anticoagulant use were identified using multivariable logistic regression. Most patients received \u3e120 days of anticoagulation, regardless of which medication was used. The median (25th-75th percentile) length of treatment for patients taking warfarin was 142 (91-234) days and for direct oral anticoagulants was 180 (101-360) days. Recurrent VTE (odds ratio [OR], 2.75 [95% CI, 1.67-4.53]), history of myocardial infarction (OR, 3.92 [95% CI, 1.32-11.7]), and direct oral anticoagulant rather than warfarin use (OR, 2.22 [95% CI, 1.59-3.08]) were independently associated with prolonged anticoagulation. Conclusions In our cohort of patients with provoked VTE, most patients received anticoagulation for longer than the guideline-recommended 3 months. This demonstrates a potential opportunity to improve care delivery and reduce anticoagulant-associated bleeding risk

Creatinine monitoring patterns in the setting of direct oral anticoagulant therapy for non-valvular atrial fibrillation

Guidelines and experts note that patients with atrial fibrillation require regular renal function monitoring to ensure safe use of direct oral anticoagulants (DOACs). Insufficient monitoring could lead to inappropriate dosing and adverse events. Our objective was to describe the frequency of insufficient creatinine monitoring among patients on DOACs, and to describe clinical factors associated with insufficient monitoring. We hypothesized that renal impairment would be associated with insufficient monitoring. A retrospective cohort study was performed with data from the Michigan Anticoagulant Quality Improvement Initiative. Patients were included if they initiated DOAC therapy for stroke prevention related to atrial fibrillation, remained on therapy for ≥ 1 year, and had baseline creatinine and weight measurements. Creatinine clearance (CrCl) was calculated via Cockcroft-Gault equation. Our outcome was the presence of insufficient creatinine monitoring, defined as: \u3c 1 creatinine level/year for patients with CrCl \u3e 50, or \u3c 2 creatinine levels/year for patients with CrCl ≤ 50. Multivariable analysis was done via logistic regression. Study population included 511 patients. In overall, 14.0% of patients received insufficient monitoring. Among patients with CrCl \u3e 50, 11.5% had \u3c 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received \u3c 2 creatinine levels/year. Baseline renal dysfunction was associated with a higher likelihood of insufficient creatinine monitoring (adjusted odds ratio 3.64, 95% confidence interval 1.81-7.29). This shows a significant gap in the monitoring of patients on DOACs-patients with renal impairment are already at higher risk for adverse events. Future studies are needed to describe the barriers in monitoring these patients and to identify how to optimally address them

Coexistence of multiuser entanglement distribution and classical light in optical fiber network with a semiconductor chip

Building communication links among multiple users in a scalable and robust way is a key objective in achieving large-scale quantum networks. In realistic scenario, noise from the coexisting classical light is inevitable and can ultimately disrupt the entanglement. The previous significant fully connected multiuser entanglement distribution experiments are conducted using dark fiber links and there is no explicit relation between the entanglement degradations induced by classical noise and its error rate. Here we fabricate a semiconductor chip with a high figure-of-merit modal overlap to directly generate broadband polarization entanglement. Our monolithic source maintains polarization entanglement fidelity above 96% for 42 nm bandwidth with a brightness of 1.2*10^7 Hz/mW. We perform a continuously working quantum entanglement distribution among three users coexisting with classical light. Under finite-key analysis, we establish secure keys and enable images encryption as well as quantum secret sharing between users. Our work paves the way for practical multiparty quantum communication with integrated photonic architecture compatible with real-world fiber optical communication network

Comparison of temporary interruption with continuation of direct oral anticoagulants for low bleeding risk procedures

INTRODUCTION: Limited data is available on the rates of bleeding and thromboembolic events for patients undergoing low bleeding risk procedures while taking direct oral anticoagulants (DOAC). METHODS: Adults taking DOAC in the Michigan Anticoagulation Quality Improvement Initiative (MAQI(2)) database who underwent a low bleeding risk procedure between May 2015 and Sep 2019 were included. Thirty-day bleeding (of any severity), thromboembolic events, and death were compared between DOAC temporarily interrupted and continued uninterrupted groups. Adverse event rates were compared using an inverse probability weighting propensity score. RESULTS: There were 820 patients who underwent 1412 low risk procedures. DOAC therapy was temporarily interrupted in 371 (45.2%) patients (601 [42.6%] procedures) and continued uninterrupted in 449 (54.8%) patients (811 [57.4%] procedures). DOAC patients with temporary interruptions were more likely to have diabetes, prior stroke or TIA, prior bleeding, higher CHA2DS2-VASc, and higher modified HAS-BLED scores. DOAC interruption was common for gastrointestinal endoscopy, electrophysiology device implantation, and cardiac catheterization while it was less common for cardioversion, dermatologic procedures, and subcutaneous injection. After propensity score adjustment, bleeding risk was lower in the DOAC temporary interruption group (OR 0.62, 95% CI 0.41-0.95) as compared to the group with continuous DOAC use. Rates of thromboembolic events and death did not differ significantly between the two groups. CONCLUSIONS: DOAC-treated patients undergoing low bleeding risk procedures may experience lower rates of bleeding when DOAC is temporarily interrupted. Prospective studies focused on low bleeding risk procedures are needed to identify the safety DOAC management strategy

Outcomes of Direct Oral Anticoagulants with Aspirin Versus Warfarin with Aspirin for Atrial Fibrillation and/or Venous Thromboembolic Disease

Introduction: The direct oral anticoagulants (DOACs) including apixaban, dabigatran, edoxaban, and rivaroxaban are increasingly utilized for the management of venous thromboembolic disease (VTE) and/or non-valvular atrial fibrillation (NVAF). Adding aspirin (ASA) to warfarin or DOAC therapy increases bleeding risk. Patients on combination therapy with ASA and an anticoagulant were not well represented in clinical trials comparing DOACs to warfarin. We sought to compare bleeding and thrombotic outcomes with DOACs and ASA compared to warfarin and ASA in a non-trial setting. Methods: We conducted a retrospective registry-based cohort study of adults on DOAC or warfarin therapy for VTE and/or NVAF. Warfarin treated patients were followed by six anticoagulation clinics. Four out of the six clinics contributed data on their patients that were on DOACs in the Michigan Anticoagulation Quality Improvement Initiative (MAQI 2) from January 2009 to June 2021. Patients were excluded if they had a history of heart valve replacement, recent myocardial infarction, or less than 3 months of follow-up. Two propensity matched cohorts (warfarin+ASA vs DOAC+ASA) of patients were analyzed based on ASA use at the time of study enrollment. The primary outcome was any new bleeding event. Secondary outcomes included new episodes of arterial or venous thrombosis, bleeding event type (major, fatal, life threatening, central nervous system, and non-major bleeding), emergency room visits, hospitalizations, transfusions, and death. Random chart audits were done to confirm the accuracy of the abstracted data. Event rates were compared using Poisson regression. Results: We identified a total of 1,139 patients on DOACs plus ASA and 4,422 patients on warfarin plus ASA. After propensity matching, we compared two groups of 1,114 matched patients. DOAC treated patients were predominately on apixaban (62.3%) and rivaroxaban (30.4%), most often at therapeutic doses (Table 1). Patients were largely (90.5%) on low dose ASA (≤ 100 mg). Patient demographics, co-morbidities, indication for anticoagulation, history of bleeding or clotting, medications, and duration of follow-up were well-balanced after matching. Patients were followed for a median of 11.7 months (interquartile range 4.4 and 34 months). Patients treated with DOAC+ASA had 2.4 thrombotic events per 100 patient years compared to 2.2 thrombotic events per 100 patient years with warfarin+ASA (P=0.78). There were no significant differences observed between groups by thrombotic subtype (stroke, transient ischemic attack, pulmonary embolism, deep vein thrombosis, table 1). Bleeding was also similar with 30.1 bleeding events per 100 patient years with DOAC+ASA compared to 27.8 bleeds per 100 patient years with warfarin+ASA (P=0.24). There were no significant differences by bleeding subtype (table 1). Hospitalizations for clotting occurred less frequently with DOAC+ASA (0.9 hospitalizations per 100 patient years) compared to warfarin+ASA (1.7 hospitalizations per 100 patient years, P=0.03). Mortality, transfusions, and healthcare utilization were otherwise similar between the two groups. Conclusions: For patients on a DOAC versus warfarin with ASA for atrial fibrillation and/or venous thromboembolic disease without a recent myocardial infarction or heart valve replacement, bleeding and thrombotic outcomes were similar