Subsequent Switching Research Articles

Novel technique of switching TIVA and sevoflurane during epilepsy surgery for combined intraoperative motor evoked potentials monitoring and electrocorticography: an illustrative case report

BackgroundDuring epilepsy surgery, it is equally important to record electrocorticography (ECoG) for detecting epileptogenic activity and guiding brain resection, and to evaluate neuromonitoring data, particularly motor evoked potentials (MEP), for avoidance of postoperative neurological complications. However, sevoflurane, which is commonly used during recording of ECoG, may attenuate the MEP response. It enforces anesthesiologists and neurosurgeons to select one anesthetic agent over another, facilitating either ECoG or MEP monitoring.Case presentationIn the presented case of a 20-year-old man, who underwent surgery for temporal lobe epilepsy, a novel technique of neuroanesthesia was introduced, integrating initial induction of the total intravenous anesthesia (TIVA) with propofol (effect-site concentration, 2.3–3.0 μg/ml), its subsequent switching to sevoflurane (end-tidal concentration, 2.5%) for ECoG recording, and further change back to TIVA for MEP monitoring during brain resection.ConclusionsIntraoperative switch of anesthetic agents according to specific intraoperative requirements may be useful for cases of brain surgery requiring both ECoG recordings and MEP monitoring.

Biogeographic history of pigeons and doves drives the origin and diversification of their parasitic body lice.

Despite their extensive diversity and ecological importance, the history of diversification for most groups of parasitic organisms remains relatively understudied. Elucidating broad macroevolutionary patterns of parasites is challenging, often limited by the availability of samples, genetic resources, and knowledge about ecological relationships with their hosts. In this study, we explore the macroevolutionary history of parasites by focusing on parasitic body lice from doves. Building on extensive knowledge of ecological relationships and previous phylogenomic studies of their avian hosts, we tested specific questions about the evolutionary origins of the body lice of doves, leveraging whole genome data sets for phylogenomics. Specifically, we sequenced whole genomes from 68 samples of dove body lice, including representatives of all body louse genera from 51 host taxa. From these data, we assembled >2,300 nuclear genes to estimate dated phylogenetic relationships among body lice and several outgroup taxa. The resulting phylogeny of body lice was well supported, although some branches had conflicting signal across the genome. We then reconstructed ancestral biogeographic ranges of body lice and compared the body louse phylogeny to phylogeny of doves, and also to a previously published phylogeny of the wing lice of doves. Divergence estimates placed the origin of body lice in the late Oligocene. Body lice likely originated in Australasia and dispersed with their hosts during the early Miocene, with subsequent codivergence and host switching throughout the world. Notably, this evolutionary history is very similar to that of dove wing lice, despite the stronger dispersal capabilities of wing lice compared to body lice. Our results highlight the central role of the biogeographic history of host organisms in driving the evolutionary history of their parasites across time and geographic space.

Predictors of treatment switching in the Big Multiple Sclerosis Data Network.

Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods. The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry. In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect. Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006). Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.

Efficacy of dose-dense versus standard neoadjuvant chemotherapy regimensin luminal HER2-negative breast cancer: Interim results of single-centre study

Introduction. The efficacy of dose-dense AC in adjuvant chemotherapy of luminal breast cancer (ER+ BC) compared with the standard dosing regimen followed by switching to taxanes has been proven in numerous clinical trials and in a large meta-analysis of the EBCTCG group. However, no study about efficiency of this regimen in neoadjuvant setting has been published.The aim of the study. To assess the effectiveness of dose-dense regimens of neoadjuvant chemotherapy (NAC) of ER + HER2-BC (4 AC once every 2 weeks (dose dense, ddAC), then 4 courses of Docetaxel once every 3 weeks or 12 weekly injections of Paclitaxel [4D/12P]) and their comparison with the standard ones (AC once every 3 weeks [ACq3w], hereinafter 4D/12P). Primary end points are complete response rate (pCR) and RCB0–I.Methods. This retrospective study included patients with resectable or locally advanced luminal HER2-negative breast cancer who received NAC from Janu 2017 to Aug 2022. Statistical hypothesis – the dose-dense regimen AC increases the frequency of RCB0–I from 22 to 32% compared to the standard dosing regimen with subsequent switching to taxanes, with a study power of 80%, ά = 0.05, 138 patients should be included in the study. A total of 315 patients were included in the study, of which 147 and 168 patients received dose-dense (ddAC) and standard chemotherapy (ACq3w), respectively. After propensity matching analysis 138 patients in each group were included in the final analysis.Results. The pCR rate was 18.84% in the ddAC group versus 14.49% in the AC q3w group, the differences were not statistically significant (p = 0.379). The frequency of RCB0–I was higher in the ddAC – group 33.33% versus 21.74% in the AC q3w (p = 0.040). According to the subgroup analysis, rate of RCB0–I was significantly higher in patients younger 50 years, cN0, with the expression of progesterone receptors in ≥ 20%.Conclusions. This is the first study to compare the efficacy of a ddAC NAC with a standard regimen for ER + HER2-BC. NAC with ddAC is associated with an increase in RCB0–I rate.

Phase field study of crack growth in t′ yttria stabilized zirconia with initial domain structures

In this paper, the fracture behavior of t′ yttria stabilized zirconia (YSZ) with initial domain structures is studied with the phase field (PF) method. Firstly, a PF model is proposed to characterize the initial domain structure and the subsequent domain switching in YSZ. After that, the PF model for domain structure evolution is coupled with the variational PF fracture model to simulate crack growth in the multi domain YSZ. The toughening effect induced by the ferroelastic domain switching is evaluated by computing the energy dissipation rate (EDR) along with the crack growth. It is shown that the internal stress field of the initial domain structure has very trivial influence on the crack growth resistance. However, the domain switching in the crack growth process can have significant influences on the fracture resistance. The domain structure evolution can bring about a local toughening or deshielding effect on the crack growth, depending on the crystal orientation. The underlying mechanisms are analyzed in detail. The proposed PF approach is efficient to study the mesoscale fracture behavior of multi domain YSZ and is helpful to assess the integrity of thermal barrier coatings.

Comparative risk perceptions of switching to JUUL vs. continued smoking and subsequent switching away from cigarettes: a longitudinal observational study

BackgroundEvidence indicates that electronic nicotine delivery systems (ENDS) pose lower risk than cigarettes; however, many smokers harbor misperceptions that ENDS are equally or more harmful, possibly deterring them from switching. This study examines whether comparative risk perceptions of JUUL vs. smoking are associated with subsequent switching, among smokers who recently purchased JUUL.MethodsN = 16,996 current established smokers who recently purchased a JUUL Starter Kit were followed 6 times over 12 months. Comparative risk perceptions were assessed using both direct and indirect measures (i.e., contrasting JUUL and smoking directly in questions, and deriving from separate absolute scales). Repeated-measures logistic regression examined switching across follow-up (no smoking in past 30 days) as a function of baseline risk perceptions, adjusting for demographics and baseline smoking behavior.ResultsPerceiving JUUL as less harmful than smoking was associated with higher switching rates, using both direct (e.g., adjusted odds ratio [AOR] = 1.48 for “JUUL much less” vs. “more/much more harmful”) and indirect (AOR = 1.07, for each 10-unit increase in fraction; AOR = 1.51 for highest (6-100) vs. lowest (0 to < 1) fraction categories) comparative risk measures (all p < 0.0001). Among the subset smoking 10 + cigarettes per day, associations between risk perceptions and switching were more pronounced (AOR = 2.51 for “JUUL much less” vs. “more/much more harmful”; AOR = 1.81 for 6-100 vs. 0 to < 1 fraction, both p < 0.0001).ConclusionsSmokers who perceive JUUL as less harmful than cigarettes have higher odds of switching. Future research should examine whether messaging which aligns comparative risk perceptions with current evidence can facilitate switching, especially among heavier smokers.

Factors influencing drug switching and changes in low-density lipoprotein-cholesterol levels with atorvastatin: a real-world observational study

BackgroundAlthough generic drugs have been approved with the assurance of interchangeable applications with original drugs, some physicians, and patients still view their efficacy and interchangeability negatively. Using real-world data, we aimed to determine factors that impact switching between drugs that contain the same active ingredient, i.e., atorvastatin, and, in turn, whether this ‘switch’ could alter clinical outcomes.MethodsUsing the National Health Insurance Service senior cohort, a retrospective cohort study was conducted to assess patients who had newly started atorvastatin 10 mg and had at least two records of national health examinations from 2010 to 2014. Drug switching, which was defined as a change in the atorvastatin product administered 90 days before the first and second examinations, was assessed. Greedy propensity score matching (1:2) was performed between switchers and non-switchers to control for potential confounders. Factors influencing switching were analyzed using multivariate logistic regression to estimate odds ratios and 95% confidence intervals (CIs). Changes in low-density lipoprotein-cholesterol (LDL-C) levels attributable to drug switching were evaluated using difference-in-differences regression.ResultsA total of 1,588 patients were included, of whom 25.3% switched drugs (1,187 non-switchers and 401 switchers). Compared to patients taking generics before the first examination, those taking the original drugs had a lower odds ratio (0.31; 95% CI [0.21, 0.46]) for subsequent drug switching. A change in medical institution was associated with a significantly higher odds ratio (6.83; 95% CI [4.66, 10.02]). There were no significant differences in LDL-C alterations between switchers and non-switchers (0.42 mg/dL; 95% CI [-2.29, 3.13]).ConclusionThe type of first-time drug administered and changes in medical institution can influence drug switching. No significant changes in LDL-C values were observed in the various switching scenarios between the original and generic drugs, suggesting their interchangeable application in real-world clinical practice.

Mind the Gap: Model-Based Switching from Selatogrel to Maintenance Therapy with Oral P2Y12 Receptor Antagonists.

Background: The P2Y12 receptor antagonist selatogrel is being developed for subcutaneous self-administration with a ready-to-use autoinjector at the onset of acute myocardial infarction (AMI) symptoms. The unique pharmacological profile of selatogrel (fast, potent, and short-acting) can bridge the time gap between the onset of AMI and first medical care. A clinical Phase 1 study showed a time-dependent pharmacodynamic interaction between selatogrel and loading doses of clopidogrel and prasugrel. As treatment switching is a common clinical practice, the assessment of subsequent switching from a clopidogrel loading dose to the first maintenance dose of oral P2Y12 receptor antagonists is highly relevant. Objectives: Model-based predictions of inhibition of platelet aggregation (IPA) for the drugs triggering pharmacodynamic interactions were to be derived to support clinical guidance on the transition from selatogrel to oral P2Y12 receptor antagonists. Methods: Scenarios with selatogrel 16 mg administration or placebo followed by a clopidogrel loading dose and, in turn, prasugrel or ticagrelor maintenance doses at different times of administration were studied. Population pharmacokinetic/pharmacodynamic modeling and simulations of different treatment scenarios were used to derive quantitative estimates for IPA over time. Results: Following selatogrel/placebo and a clopidogrel loading dose, maintenance treatment with ticagrelor or a prasugrel loading dose followed by maintenance treatment quickly achieved sustained IPA levels above 80%. Prior to maintenance treatment, a short time span from 18 to 24 h was identified where IPA levels were predicted to be lower with selatogrel than with placebo if clopidogrel was administered 12 h after selatogrel or placebo. Predicted IPA levels reached with placebo alone and a clopidogrel loading dose at 4 h were consistently lower than with selatogrel administration, followed by a clopidogrel loading dose at 12 h. If a clopidogrel loading dose is administered at 12 h, selatogrel maintains higher IPA levels up to 16 h. IPA levels are subsequently lower than on the placebo until the administration of the first maintenance dose. Conclusions: Model-based predictions informed the transition from selatogrel subcutaneous administration to oral P2Y12 therapy. The application of modeling techniques illustrates the value of employing pharmacokinetic and pharmacodynamic modeling for the simulation of various clinical scenarios of switching therapies.

Physiological trade-off of marine fish under Zn deficient and excess conditions

Fish can regulate their Zn body bioaccumulation, but the mechanisms and physiological responses at the organ level are still largely unknown. In the present study, we exposed the marine seabreams under different Zn levels (deficient, optimum and excess levels) over a period of 4 weeks and examined how fish maintained its regulation of bioaccumulation with associated physiological effects at the fish intestinal organ. Our results indicated that fish intestinal organs constantly controlled the Zip family to “rob” more Zn under Zn-deficiency (with a dietary level of 7.9 mg/kg), whereas restricted the Zn efflux to preserve the intestinal function. Under Zn-excess conditions (193.3 mg/kg), the fish intestine maintained a limited Zn homeostasis (37.8–44.6 μg/mg) by initially inhibiting the influx through the Zip family receptor, but later accelerating both influx and efflux of Zn. Based on the WGCNA method, Zn deficient dietary exposure first resulted in defense response with subsequent switching to antioxidant defense. Instead, excess Zn first triggered the immunological response, but then led to physiological toxicity (abnormal in lipid metabolism). Although Zn had multiple biological functions, it was preferentially involved in lipid metabolism under different dietary Zn doses. This study provided direct evidence for Zn regulation at the organ level and detoxification mechanisms against potential environmental toxicity in fish.

The flow and heat transfer behavior of synthetic jets with star shaped orifice of different lobes

In the present experimental investigation, the flow and heat transfer characteristics of synthetic jet (SJ) issuing from different lobed (3–10) star-shaped orifices are studied. Tests are performed by actuating the SJ actuator at constant input power of 4Vrms, with varied range of orifice to surface spacings (1–16) and numerous values of Reynolds number (8692–10746). The synthetic jet's flow characteristics are studied using hot-wire anemometry, while the thermal characteristics are analyzed using an IR camera. Distinct peaks in turbulence intensity are observed in major and minor planes for different lobed (3–6) star orifices; this may be due to the development of two shear layers in such orifices, which consequently merges into a single shear layer for higher lobed (8–10) star orifice. The 6-lobed star orifice is found to exhibit maximum heat transfer performance at z/d varying between 2 and 14. At z/d = 2, the 6-lobed star orifice exhibit 7.6% and 10.1% improvement in average Nusselt number compared to circular and 10-lobed star orifice respectively, which may be due to formation of vortical structures along the lobed edges and subsequent switching of axes between the major and minor planes. To comprehend the energy associated with the issuing vortices, the power spectral density of the velocity signal at the orifice exit is examined. A unified correlation for the average Nusselt number is also derived for various star-shaped orifices.

On the operation of switchable oxygen depolarized cathodes

The electrochemical chlor-alkali electrolysis remains an energy-intensive production process even though many improvements have been developed over the last decades. Oxygen depolarized cathodes (ODC) reduce energy consumption by approximately 25% while oxygen is consumed instead of hydrogen being evolved. The switchable ODC (sODC) facilitates the oxygen-consuming and the conventional hydrogen-evolving modes with the same electrode. In this study, we investigate sODCs for demand-side electrolysis by switching between modes. Experimental investigations covered current densities ranging from 50mAcm−2 to 525mAcm−2, and we evaluated the long-term effect of switching between the two modes on the system's stability. In addition, cell potential, Faraday efficiency and contact angle measurements were compared for pristine and used sODCs after up to 1600 switching cycles. The lab cell was implemented in 3D-CFD simulations to investigate a nitrogen flushing process between the two modes to prevent the formation of explosive mixtures in the electrolyzer. sODCs showed a stable and continuously high Faraday efficiency. However, an increase in cell potential over 1000 switching cycles of up to 7.8% was observed, which was attributed to electrolyte flooding. Still, the sODC is well comparable to the conventional ODC with a marginal difference in cell potential (0.07V), which demonstrates its high potential for industrial application. 3D-CFD simulations were compared to experimental flushing time measurements. We implemented the resulting flushing times for a safe operation in the subsequent switching cycles. The verified CFD simulations can help to further optimize the flushing procedure for an economically feasible switching process in industry-sized cells. Switchable electrodes enable flexibility to react to fluctuating boundary conditions such as the electricity price and can be implemented in many processes beyond the chlor-alkali electrolysis.

Opioid agonist therapy switching among individuals with prescription-type opioid use disorder: Secondary analysis of a pragmatic randomized trial

BackgroundEngagement and retention in opioid agonist therapy (OAT) remains a challenge. This study evaluated the impact of initial randomized OAT allocation on subsequent switching among people with prescription-type opioid use disorder (POUD). MethodsSecondary analysis of a 24-week Canadian multicenter, pragmatic, randomized trial conducted between 2017 and 2020 comparing flexible take-home buprenorphine/naloxone versus supervised methadone models of care for POUD. We used Cox Proportional Hazards modeling to assess for impact of treatment assignment on time to OAT switching, adjusting for important confounders. For clinical correlates, we analyzed data from baseline questionnaires on demographic, substance use, and health factors as well as urine drug screen. ResultsOf 272 randomized participants, 210 initiated OAT within 14 days per trial protocol, of whom 103 participants were randomized to buprenorphine/naloxone and 107 to methadone. Within 24-week follow-up, 41 (20.5%) of all participants switched OAT with 25 (24.3%, median 27 days, 88.4 per 100 person-years) and 16 participants (15.0%, median 53.5 days, 46.1 per 100 person-years) switching from buprenorphine/naloxone and methadone arms, respectively. In adjusted analysis, allocation to buprenorphine/naloxone was associated with significantly higher risk of switching (aHR = 2.31, 95% CI 1.22 – 4.38). ConclusionsOAT switching was common in this sample of individuals with POUD, with individuals randomly allocated to buprenorphine/naloxone being more than twice as likely to switch versus methadone. This may reflect a stepped care approach in OUD management. More research is needed to evaluate overall retention and outcomes with the different observed risks of switching between methadone and buprenorphine/naloxone.

The clinical and Practice Dilemma of Frequent Switching Among Generic Medications: Magnitude and Patient Safety Prospective.

Objective: To assess the magnitude of generic-generic and brand-generic medication switching and its impact on patients' understanding and the potential risk of medication errors. Methods: The study composed of 2 parts. The first part is a retrospective study to measure the frequency of medications switching in King Faisal Specialist Hospital and Research Centre (KFSH&RC), from 1st of January 2015 to the 31st of December, 2020. Brand medications that were switched to generic medications, generic medications that were switched to brand medications and generic medications that were switched to other generic medications were included. Medications that were switched before or after the study period were excluded. The primary outcomes are the total percentage of switching from brand to generic of all medications in KFSH&RC drug formulary, frequency of generic-generic medications switching and percentage of switching back from generic to brand medications. The second part is a cross sectional survey-based study to assess patients' understanding of their medications and the potential for medication errors by assessing their ability to identify the discrepancies and duplications utilizing a validated questionnaire. Results: Over 5 years, the number of generic medications increased from 553 (35.5%) to 640 (41.1%) out of the 1554 formulary items. Percentage of switching from brand to generic over that 5-year period was 15.9%. Percentage of switching back from generic to brand was 12.8%. Total number of generic medications that had been switched to other generic medications was 256 (16.5%). Out of the 218 patients who had been switched from generic to generic medication, only 43 patients (19.7%) knew the indication for the generic medication they were taking. One hundred forty-six patients (67%) knew the indication of generic medications exclusively by their physical "trademark" characteristics, with 11.5% unrecognized duplication. Conclusion: There is a clear tendency to switch brand medications to generics and to switch between generics. We found the percentage of subsequent switching back to branded products is alarming. Frequent switching between medications negatively impacted patient comprehension and resulted in medication duplication. There is a crucial need for appropriate medication counseling and medication use ecosystem redesign.

Adaptive Fuzzy Asynchronous Control for Nonhomogeneous Markov Jump Power Systems Under Hybrid Attacks

This article investigates the adaptive fuzzy asynchronous control problem for discrete-time nonhomogeneous Markov jump power systems under hybrid attacks. A nonhomogeneous Markov process is used to describe the phenomenon of transient failures occurring in power lines and subsequent switching of associated circuit breakers. The corresponding nonhomogeneous hidden Markov model is utilized to detect the jump modes of power systems. Both deception attack and denial-of-service attack are analyzed simultaneously owing to the vulnerability of power systems. With detected modes and fuzzy logic systems, an adaptive fuzzy asynchronous control strategy is proposed. Using the mode-dependent Lyapunov function, the existence conditions of the desired controller law are obtained such that the closed-loop power systems are bounded stable in the mean-square sense. Finally, the usefulness of the developed control strategy is demonstrated by a numerical example.

Einfluss der Stillstandszeit auf das Losreißmoment nasslaufender Lamellenkupplungen

Detailed knowledge of the influences on the frictional behavior is crucial for reliable operation of safety-relevant, wet-running multi-plate clutches. The breakaway torque is of particular interest for safety-critical applications such as safety brakes and clutches. While influences of the tribological system by variation of friction partners, lubricant and operating conditions are usually the focus of current investigations, the influence of the time of standstill between a preceding tribological load and a subsequent breakaway of the wet disk clutch is not considered. To determine this influence, experimental investigations are carried out on a component test rig. For this purpose, the time of standstill of the clutch is systematically varied after preceding load shifts and the clutch is then broken away. During these investigations, it is shown that the downtime of multi-plate clutches with sinter friction lining has considerable influence on the frictional behavior in the first switching operations after actuation. An influence can already be clearly seen at a standstill time of approximately 15 minutes. An increase in the maximum friction coefficient occurring at the start of the slip switching operation compared with subsequent slip switching operations was observed, which can be attributed to the downtime after a defined preload. Influences of the disk temperature are considered by measuring the outer disk temperature. The influence is attributed to the change of the boundary layer during the standstill. The results provide a contribution to the transferability of investigations of the friction behavior of component test rigs to real applications in which the friction system is exposed to relevant times of standstill and expand the existing knowledge base on test methods.

A nationwide study of compliance of venoactive drugs in chronic venous disease patients.

Venoactive drugs are widely used to improve the symptoms and signs of chronic venous disease. This study aimed to analyze the rate of adverse events after venoactive drug prescription and subsequent compliance and switching rates. Using the National Health Insurance Service database, individuals with at least one chronic venous disease code between January 2009 and December 2019 were identified, and 30% (2,216,780 individuals) of these were sampled. Finally, 1,551,212 patients were included, and we analyzed adverse events, compliance, and switching rates with 8 venoactive drugs, including Vitis vinifera extract, naftazone, micronized purified flavonoid fraction, Vitis vinifera leaf extract, diosmin, diobsilate calcium, bilberry fruit dried extract, and sulodexide. The most commonly prescribed venoactive drug was Vitis vinifera extract (72.2%), followed by sulodexide (9.3%), and Vitis vinifera leaf dry extract (8.2%). Adverse event rates were significantly lower in the naftazone and diosmin groups (P = 0.001 and P = 0.002, respectively) and significantly higher in the Vitis vinifera leaf dry extract group (P = 0.009). Drug adherence to sulodexide was the highest throughout the study period, followed by billberry extract and dobesilate (all P < 0.001). For most drugs, the drug switching rate was low (<5.0%). Vitis vinifera extract was the most commonly prescribed venoactive drug in Korea, and drug adherence to sulodexide was the highest among all venoactive drugs. The adverse event rates were significantly lower in the naftazone and diosmin groups.

THROMBOLYSIS IN PULMONARY EMBOLISM TREATMENT.

The aim: To assess the effectiveness of thrombolytic therapy in treatment pulmonary embolism. Materials and methods: The work analyzed the results of the survey and conservative treatment of 284 patients with pulmonary embolism treated in cardiological department in «Uzhgorod Central City Clinical Hospital» during 2019-2022. Patients were divided into two groups: group I - 250 (88%) patients received anticoagulant therapy; group II - 34 (12%) patients received thrombolytic therapy that was then switched to new oral anticoagulants. Results: In I group, the first three days were carried out continuously intravenous infusion of heparin in a dose of 25-30 thousand units per day, on the fourth day switched to subcutaneous injection for 10-14 days with subsequent switching to rivaroxaban. 34 (12.0%) patients of the II group, was started with thrombolytic therapy. 32 (94.1%) patients were prescribed alteplase 100 mg/day, and 2 (5.9%) patients - streptokinase 1.5 million units/day. After thrombolysis, patients were prescribed rivaroxaban for prolonged period. Thrombolytic therapy made it possible to prevent fatal cases, and in monotherapy with anticoagulants - mortality was 4.8%. Minor hemorrhagic complications like hematuria, local hematomas at the injection site, bleeding gums were observed in 7.6% of patients during thrombolytic therapy. No cases of large hemorrhages were observed. Manifestations of chronic postembolic pulmonary hypertension in the distant period were found in 97.1% and 6.9% of patients of the I and II groups, respectively. Lethality in the remote period was 5.3% - all in the 1st group of patients due to PE recurrence and acute myocardial infarction. Conclusions: Implementation of thrombolytic therapy in patients with thromboembolism of the pulmonary artery allows effectively prevent recurrence with a fatal outcome, restore the lumen of the pulmonary arteries and prevent the development of chronic postembolic pulmonary hypertension in the immediate and remote period of observation compared to isolated anticoagulant therapy.

Domain structure evolution during polarization reversal in calcium orthovanadate single crystals

We have switched polarization in calcium orthovanadate single crystal with as-grown domain structure consisting of isolated domains with charged domain walls (CDWs) located in the bulk using pretreatment by ac field and subsequent switching in dc field at the elevated temperature. The formation of the domain ledges at the CDW in the bulk and their growth in the polar direction has been revealed. The isolated domains with optically well-defined walls appeared when the ledge tops reached the surface, their shape and sizes remaining constant during further switching. Unlike usual continuous domain wall motion, we have observed the discrete switching by arising of the isolated domains without any input of the traditional domain nucleation at the polar surface. The obtained results have been explained under the assumption that at the used experimental conditions, the applied field is above the threshold value for ledge nucleation at CDW in the bulk, but below the threshold for domain wall motion at the surface. Thus, we have obtained the discrete switching by ledge growth without any sideways motion of the domain walls and domain coalescence. The nonuniform evolution of the domain structure at the surface is due to the dependence of the switching rate on the distance from CDW to the polar surface, which is random in the studied domain structure.

Mechanically tunable elastic modulus of freestanding Ba1−xSrxTiO3 membranes via phase-field simulation

The freestanding ferroelectric membranes with super-elasticity show promising applications in flexible electronic devices such as transducers, memories, etc. While there have been recent studies on the effect of mechanical bending on the domain structure evolutions and phase transitions in ferroelectric membranes, its influence on Young's modulus of these freestanding membranes is less explored, which is crucial for the design and application of flexible electronics. Here, a phase-field model is developed to simulate the tunability of Young's modulus of freestanding Ba1−xSrxTiO3 membranes under mechanical bending. It is demonstrated that the bended membrane shows a uniform Young's modulus compared with unbended membrane. By increasing the bending angle, Young's modulus tunability is enhanced, which can be attributed to the vortex-like domain structures induced by the mechanical bending. These vortex-like domains with large domain wall energy inhibit the subsequent domain switching under externally applied tensile strain and reduce the eigenstrain variation, which leads to a large Young's modulus. In addition, the formation of vortex domain structure is suppressed with increasing Sr2+ content in Ba1−xSrxTiO3 membranes at the same bending degree, resulting in a decrease in Young's modulus tunability. Our work reveals that the tunability of Young's modulus of freestanding ferroelectric membranes can be achieved by mechanical bending, which provides guidance for designing flexible electronic devices.

Surface-Dominated HfO2 Nanorod-Based Memristor Exhibiting Highly Linear and Symmetrical Conductance Modulation for High-Precision Neuromorphic Computing.

The switching characteristics and performance of oxide-based memristors are predominately determined by oxygen- or oxygen-vacancy-mediated redox reactions and the consequent formation of conducting filaments (CFs). Devices using oxide thin films as the switching layer usually require an electroforming process for subsequent switching operations, which induces large device-to-device variations. In addition, the hard-to-control redox reaction during repeated switching causes random fluctuations or degradation of each resistance state, hindering reliable switching operations. In this study, an HfO2 nanorod (NR)-based memristor is proposed for simultaneously achieving highly uniform, electroforming-free, fast, and reliable analogue switching properties. The well-controlled redox reaction due to the easy gas exchange with the environment at the surface of the NRs enhances the generation of oxygen or oxygen vacancies during the switching operation, resulting in electroforming-free and reliable switching behavior. In addition, the one-dimensional surface growth of CFs facilitates highly linear conductance modulation with smaller conductance changes compared with the two-dimensional volume growth in thin-film-based memristors, resulting in a high accuracy of >92% in the Modified National Institute of Standards and Technology pattern-recognition test and desirable spike-timing-dependent plasticity.