scholarly journals Efficient removal of apixaban with extracorporeal hemoadsorption

2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
R Tripathi ◽  
J Morales ◽  
O Ortiz ◽  
V Lee ◽  
V Capponi ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Plasma Concentration ◽  
Whole Blood ◽  
Porous Polymer ◽  
Private Company ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Drug Removal ◽  
Surgical Bleeding ◽  
Over Time

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): CytoSorbents Medical Incorporation Background A hemadsorption device containing biocompatible porous polymer beads is easily incorporated into extracorporeal circuits including cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT), and hemoperfusion. This device has been shown to safely and effectively remove the P2Y12 receptor antagonist ticagrelor and the direct oral anticoagulant (DOAC) rivaroxaban during CPB in patients undergoing emergent cardiac surgery.  Importantly, drug removal was associated with significant reductions in surgical bleeding and improved clinical outcomes resulting in CE Mark approval. Apixaban, another DOAC, has gained increasing popularity given its proven efficacy and lower risk of bleeding in clinical use. However, a pressing unmet medical need exists for the mitigation of the bleeding risk encountered in patients on apixaban who require urgent or emergent surgery. Currently approved reversal agents are only indicated in the case of uncontrolled or life-threatening bleeding, but not as preventive measures to mitigate surgical bleeding. Purpose To demonstrate the ability of the extracorporeal hemoadsorption device to remove apixaban from whole blood. Methods The hemoadsorption device was evaluated for removal of apixaban in an in vitro benchtop model using bovine whole blood. The 4L of blood were continuously circulated through a 300 mL porous polymer device over 6 hours at a flow rate of 300 mL/min to evaluate the drug removal kinetics of apixaban. Starting apixaban concentration of 300ng/mL was utilized in the model to reflect standard therapeutic levels. Plasma levels of apixaban over time were measured using liquid chromatography with tandem mass spectrometry (LC-MS-MS). A control setup utilized an identical flow circuit, minus the hemoadsorption device. Results Mean plasma concentration of apixaban was reduced to ∼9.1 ng/mL (equivalent to ∼96.3% removal) over the first 60 min of hemoperfusion with the device. Specifically, mean percent remaining plasma concentration of apixaban following device treatment was 42.2%, 18.6%, 8% and 3.7% after 15, 30, 45 and 60 min of therapy, respectively. Overall, ∼99.7% blood concentration of apixaban was removed over the total 6 h. Drug concentrations remained unchanged in the control circuit, with a statistically significant difference between the control and treatment groups at all time points except 0 h (p < 0.01). Conclusion Apixaban is efficiently removed with hemoadsorption using porous polymer device technology. Drug concentrations were reduced >96% after 60 min. Similarly, efficient benchtop removal utilizing the same technology was observed for ticagrelor and rivaroxaban, and subsequently translated into significant clinical benefit in patients requiring emergent cardiac surgery. The results of the current study hold significant promise for the future clinical applicability of apixaban removal. Abstract Figure. Percent of remaining apixaban over time

Clinical Impact of Co-medication of Levetiracetam and Clobazam with Proton Pump Inhibitors: A Drug Interaction Study

2020 ◽  
Vol 21 (2) ◽  
pp. 126-131
Author(s):  
Bhuvanachandra Pasupuleti ◽  
Vamshikrishna Gone ◽  
Ravali Baddam ◽  
Raj Kumar Venisetty ◽  
Om Prakash Prasad
Keyword(s):  
Plasma Concentration ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Plasma Concentrations ◽  
Control Group ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Post Hoc ◽  
Hydrolysis Of ◽  
Cytochrome P 450

Background: Clobazam (CLBZ) metabolized primarily by Cytochrome P-450 isoenzyme CYP3A4 than with CYP2C19, Whereas Levetiracetam (LEV) is metabolized by hydrolysis of the acetamide group. Few CYP enzymes are inhibited by Proton Pump Inhibitors (PPIs) Pantoprazole, Esomeprazole, and Rabeprazole in different extents that could affect drug concentrations in blood. The aim of the present study was to evaluate the effect of these PPIs on the plasma concentrations of LEV and CLBZ. Methods: Blood samples from 542 patients were included out of which 343 were male and 199 were female patients and were categorized as control and test. Plasma samples analyzed using an HPLC-UV method. Plasma concentrations were measured and compared to those treated and those not treated with PPIs. One way ANOVA and games Howell post hoc test used by SPSS 20 software. Results: CLBZ concentrations were significantly 10 folds higher in patients treated with Pantoprazole (P=0.000) and 07 folds higher in patients treated with Esmoprazole and Rabeprazole (P=0.00). Whereas plasma concentration of LEV control group has no statistical and significant difference when compared to pantoprazole (P=0.546) and with rabeprazole and esomeprazole was P=0.999. Conclusion: The effect of comedication with PPIs on the plasma concentration of clobazam is more pronounced for pantoprazole to a greater extent when compared to esomeprazole and rabeprazole. When pantoprazole is used in combination with clobazam, dose reduction of clobazam should be considered, or significance of PPIs is seen to avoid adverse effects.

scholarly journals A leadless pacemaker in the real-world setting: Patient profile and performance over time

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
C Garweg ◽  
N Clementy ◽  
P Mondoloy ◽  
S Winter ◽  
P Bordachar ◽  
...  
Keyword(s):  
Pericardial Effusion ◽  
Success Rate ◽  
Patient Characteristics ◽  
Effusion Rate ◽  
Private Company ◽  
Patient Profile ◽  
Leadless Pacemaker ◽  
Number Of Patients ◽  
Significant Difference ◽  
Over Time

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic, Inc. OnBehalf Micra Acute Performance EMEA Investigators Background The first in-man implant of the Micra leadless pacemaker occurred in December 2013. While prior trials demonstrated a high implant success rate and favorable safety and efficacy results; whether the patient population and outcomes have changed over time is not well studied. Purpose To characterize the evolution of patient profile and outcomes for patients receiving a leadless pacemaker through the pre-market and post-market environment. Methods Patients undergoing a Micra leadless pacemaker implant attempt from the initial Micra Investigational Device Exemption [IDE] and current Micra studies (Micra post-approval registry [PAR], Micra acute performance [MAP] study) were analyzed. Patient characteristics and pericardial effusions regardless of severity were summarized. Results The 3466 patients included in the analysis underwent a Micra implant attempt and were enrolled during consecutive timeframes: patients from the Micra IDE study (n = 726) underwent a Micra implant attempt from 2013-2015, patients from the PAR (n = 1814) from 2015-2018, and patients from Micra MAP cohort (n = 926) from 2018 – 2020.  Implant success was >99.0% in all 3 studies. Median age ranged from 78 – 79 years among the 3 studies without significant difference. There were more patients requiring dialysis in the MAP cohort compared to the PAR or IDE cohorts (10.3%, 7.9%, and 3.9%, respectively; P < 0.001), but fewer patients with congestive heart failure (8.3%, 13.1%, and 18.0%; P < 0.001). Pacing indication was significantly different between the studies, with fewer patients in MAP having an indication of bradyarrhythmia associated with atrial fibrillation (AF) and more having an indication associated with atrioventricular block without AF (P < 0.001). The number of patients considered to be precluded for a transvenous pacemaker implant increased significantly from the initial IDE study to the PAR and MAP studies (6.2%, 23.9%, and 44.1%, respectively, P < 0.001).  Implant site placement was mostly apical for the IDE but shifted to mostly septal placement in the PAR and MAP (septal placement: 33.3%, 64.0%, and 79.5%, respectively). The rate of pericardial effusion regardless of severity was 1.79% (n = 13) in the IDE, 0.83% (n = 15) in the PAR, and 0.97% (n = 9) in MAP (figure). Mean pacing thresholds among MAP EMEA patients were low (0.61 ± 0.40V) at implant and remained stable through 12 months (0.62 +/- 0.41V). Conclusion Despite patient differences over time, the Micra leadless pacemaker was implanted with a high success rate and a low perforation rate, in-line with prior reports. Abstract Figure. Pericardial effusion rate by study

Macroaggregation of Platelets in Plasma, as Distinct from Microaggregation in Whole Blood (and Plasma), as Determined Using Optical Aggregometry and Platelet Counting respectively, is Specifically Impaired following Cardiopulmonary Bypass in Man

1994 ◽  
Vol 72 (04) ◽  
pp. 511-518 ◽  
Author(s):  
Valentine C Menys ◽  
Philip R Belcher ◽  
Mark I M Noble ◽  
Rhys D Evans ◽  
George E Drossos ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Platelet Count ◽  
Cardiopulmonary Bypass ◽  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Interquartile Range ◽  
Contributory Factor ◽  
Platelet Aggregability ◽  
Aggregate Growth

SummaryWe determined changes in platelet aggregability following cardiopulmonary bypass, using optical aggregometry to assess macroaggregation in platelet-rich plasma (PRP), and platelet counting to assess microaggregation both in whole blood and PRP. Hirudin was used as the anticoagulant to maintain normocalcaemia.Microaggregation (%, median and interquartile range) in blood stirred with collagen (0.6 µg/ml) was only marginally impaired following bypass (91 [88, 93] at 10 min postbypass v 95 (92, 96] prebypass; n = 22), whereas macroaggregation (amplitude of response; cm) in PRP stirred with collagen (1.0µg/ml) was markedly impaired (9.5 [8.0, 10.8], n = 41 v 13.4 [12.7,14.3], n = 10; p <0.0001). However, in PRP, despite impairment of macroaggregation (9.1 [8.5, 10.1], n = 12), microaggregation was near-maximal (93 [91, 94]), as in whole blood stirred with collagen. In contrast, in aspirin-treated patients (n = 14), both collagen-induced microaggregation in whole blood (49 [47, 52]) and macroaggregation in PRP (5.1 [3.8, 6.6]) were more markedly impaired, compared with control (both p <0.001).Similarly, in PRP, macroaggregation with ristocetin (1.5 mg/ml) was also impaired following bypass (9.4 [7.2, 10.7], n = 38 v 12.4 [10.0, 13.4]; p <0.0002, n = 20), but as found with collagen, despite impairment of macroaggregation (7.2 [3.5,10.9], n = 12), microaggregation was again near-maximal (96 [93,97]). The response to ristocetin was more markedly impared after bypass in succinylated gelatin (Gelo-fusine) treated patients (5.6 [2.8, 8.6], n = 17; p <0.005 v control), whereas the response to collagen was little different (9.3 v 9.5). In contrast to findings with collagen in aspirin-treated patients, the response to ristocetin was little different to that in controls (8.0 v 8.3). Impairment of macroaggregation with collagen or ristocetin did not correlate with the duration of bypass or the platelet count, indicating that haemodilution is not a contributory factor.In conclusion: (1) Macroaggregation in PRP, as determined using optical aggregometry, is specifically impaired following bypass, and this probably reflects impairment of the build-up of small aggregates into larger aggregates. (2) Impairment of aggregate growth and consolidation could contribute to the haemostatic defect following cardiac surgery.

Viscosity and Red Cell Deformity in Arterial Disease

1979 ◽  
Author(s):  
G Cella ◽  
H de Haas ◽  
M Rampling ◽  
V Kakkar
Keyword(s):  
Vascular Disease ◽  
Blood Viscosity ◽  
Whole Blood ◽  
Arterial Disease ◽  
Plasma Viscosity ◽  
Control Group ◽  
Fibrinogen Concentration ◽  
Red Cell ◽  
Whole Blood Viscosity ◽  
Significant Difference

Haemorrheological factors have been shown to be affected in many kings of vascular disease. The present study was undertaken to correlate these factors in normal subjects and patients suffering from peripheral arterial disease. Twenty-two patients were investigated; they had moderate or severe intermittent claudication, extent of disease being confirmed by aorto-arteriography and ankle-systolic pressure studies. Twenty-five controls with no symptoms or signs of arterial disease were selected with comparable age and sex distribution. Whole blood viscosity was measured at shear rates of 230 secs-1 and 23 secs-lat 37°c using a Wells Brookfield cone plate microvisco meter. Plasma viscosity was also measured in an identical manner. Erythrocyte flexibility was measured by centrifuge technique and fibrinogen concentration as well as haematocrit by standard techniques. The fibrinogen concentration appeared to be the only significant parameter; the mean concentration in patients with peripheral vascular disease of 463 ± 73mg/l00ml in the control group ( < 0.05). Although whole blood viscosity was high in patients, when corrected to a common haematocrit, there was no significant difference between patients and controls. The same megative correlation was found for plasma viscosity. The red cell flexibility was found to be increased in patients as compared to the control group, but this effect appeared to be simply proportional to the fibrinogen concentration.

Anti-Diarrheal Drug Repositioning in Tumour Cell Cytotoxicity

2019 ◽  
Vol 19 (8) ◽  
pp. 1037-1047 ◽  
Author(s):  
Jihene Elloumi-Mseddi ◽  
Dhouha Msalbi ◽  
Raouia Fakhfakh ◽  
Sami Aifa
Keyword(s):  
Side Effects ◽  
Anticancer Drugs ◽  
Tumour Cell ◽  
Caspase 3 ◽  
Drug Repositioning ◽  
Brdu Incorporation ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Ic50 Values ◽  
Mcf 7

Background:Drug repositioning is becoming an ideal strategy to select new anticancer drugs. In particular, drugs treating the side effects of chemotherapy are the best candidates.Objective:In this present work, we undertook the evaluation of anti-tumour activity of two anti-diarrheal drugs (nifuroxazide and rifaximin).Methods:Anti-proliferative effect against breast cancer cells (MDA-MB-231, MCF-7 and T47D) was assessed by MTT analysis, the Brdu incorporation, mitochondrial permeability and caspase-3 activity.Results:Both the drugs displayed cytotoxic effects on MCF-7, T47D and MDA-MB-231 cells. The lowest IC50 values were obtained on MCF-7 cells after 24, 48 and 72 hours of treatment while T47D and MDA-MB-231 were more resistant. The IC50 values on T47D and MDA-MB-231 cells became significantly low after 72 hours of treatment showing a late cytotoxicity effect especially of nifuroxazide but still less important than that of MCF-7 cells. According to the IC50 values, the non-tumour cell line HEK293 seems to be less sensitive to cytotoxicity especially against rifaximin. Both the drugs have shown an accumulation of rhodamine 123 as a function of the rise of their concentrations while the Brdu incorporation decreased. Despite the absence of a significant difference in the cell cycle between the treated and non-treated MCF-7 cells, the caspase-3 activity increased with the drug concentrations rise suggesting an apoptotic effect.Conclusion:Nifuroxazide and rifaximin are used to overcome the diarrheal side effect of anticancer drugs. However, they have shown to be anti-tumour drugs which make them potential dual effective drugs against cancer and the side effects of chemotherapy.

scholarly journals Engineering students’ attitudinal beliefs by gender and student division: a methodological comparison of changes over time

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Madison E. Andrews ◽  
Anita D. Patrick ◽  
Maura Borrego
Keyword(s):  
Self Efficacy ◽  
Engineering Students ◽  
Focal Point ◽  
Value Engineering ◽  
Longitudinal Analyses ◽  
Utility Value ◽  
Cross Sectional ◽  
Targeted Interventions ◽  
Significant Difference ◽  
Over Time

Abstract Background Students’ attitudinal beliefs related to how they see themselves in STEM have been a focal point of recent research, given their well-documented links to retention and persistence. These beliefs are most often assessed cross-sectionally, and as such, we lack a thorough understanding of how they may fluctuate over time. Using matched survey responses from undergraduate engineering students (n = 278), we evaluate if, and to what extent, students’ engineering attitudinal beliefs (attainment value, utility value, self-efficacy, interest, and identity) change over a 1-year period. Further, we examine whether there are differences based on gender and student division, and then compare results between cross-sectional and longitudinal analyses to illustrate weaknesses in our current understanding of these constructs. Results Our study revealed inconsistencies between cross-sectional and longitudinal analyses of the same dataset. Cross-sectional analyses indicated a significant difference by student division for engineering utility value and engineering interest, but no significant differences by gender for any variable. However, longitudinal analyses revealed statistically significant decreases in engineering utility value, engineering self-efficacy, and engineering interest for lower division students and significant decreases in engineering attainment value for upper division students over a one-year period. Further, longitudinal analyses revealed a gender gap in engineering self-efficacy for upper division students, where men reported higher means than women. Conclusions Our analyses make several contributions. First, we explore attitudinal differences by student division not previously documented. Second, by comparing across methodologies, we illustrate that different conclusions can be drawn from the same data. Since the literature around these variables is largely cross-sectional, our understanding of students’ engineering attitudes is limited. Our longitudinal analyses show variation in engineering attitudinal beliefs that are obscured when data is only examined cross-sectionally. These analyses revealed an overall downward trend within students for all beliefs that changed significantly—losses which may foreshadow attrition out of engineering. These findings provide an opportunity to introduce targeted interventions to build engineering utility value, engineering self-efficacy, and engineering interest for student groups whose means were lower than average.

scholarly journals Quality of life assessments in clinical practice using either the EORTC-QLQ-C30 or the SEIOQL-DW: a randomized study

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Åsa Kettis ◽  
Hanna Fagerlind ◽  
Jan-Erik Frödin ◽  
Bengt Glimelius ◽  
Lena Ring
Keyword(s):  
Quality Of Life ◽  
Clinical Practice ◽  
Significant Difference ◽  
Patient Reported ◽  
Health Related Qol ◽  
Health Related ◽  
Secondary Outcomes ◽  
The Impact ◽  
Over Time

Abstract Background Effective patient-physician communication can improve patient understanding, agreement on treatment and adherence. This may, in turn, impact on clinical outcomes and patient quality of life (QoL). One way to improve communication is by using patient-reported outcome measures (PROMs). Heretofore, studies of the impact of using PROMs in clinical practice have mostly evaluated the use of standardized PROMs. However, there is reason to believe that individualized instruments may be more appropriate for this purpose. The aim of this study is to compare the effectiveness of the standardized QoL-instrument, the European Organization for Research and Treatment of Cancer Quality of Life C-30 (EORTC-QOL-C30) and the individualized QoL instrument, the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), in clinical practice. Methods In a prospective, open-label, controlled intervention study at two hospital out-patient clinics, 390 patients with gastrointestinal cancer were randomly assigned either to complete the EORTC-QOL-C30 or the SEIQoL-DW immediately before the consultation, with their responses being shared with their physician. This was repeated in 3–5 consultations over a period of 4–6 months. The primary outcome measure was patients’ health-related QoL, as measured by FACIT-G. Patients’ satisfaction with the consultation and survival were secondary outcomes. Results There was no significant difference between the groups with regard to study outcomes. Neither intervention instrument resulted in any significant changes in health-related QoL, or in any of the secondary outcomes, over time. This may reflect either a genuine lack of effect or sub-optimization of the intervention. Since there was no comparison to standard care an effect in terms of lack of deterioration over time cannot be excluded. Conclusions Future studies should focus on the implementation process, including the training of physicians to use the instruments and their motivation for doing so. The effects of situational use of standardized or individualized instruments should also be explored. The effectiveness of the different approaches may depend on contextual factors including physician and patient preferences.

Carbon Dioxide Equilibration in Canine Lungs during Rebreathing and Acute Alkalosis

1979 ◽  
Vol 57 (5) ◽  
pp. 385-388 ◽  
Author(s):  
R. D. Latimer ◽  
G. Laszlo
Keyword(s):  
Whole Blood ◽  
Base Excess ◽  
Venous Blood ◽  
Main Pulmonary Artery ◽  
Mixed Venous Blood ◽  
Arterial Blood ◽  
Significant Difference ◽  
Venous Pco2 ◽  
Pulmonary Arterial ◽  
Gas Pressures

1. The left lower lobe of the lungs of six anaesthetized dogs were isolated by the introduction of a bronchial cannula at thoracotomy. Catheters were introduced into the main pulmonary artery and a vein draining the isolated lobe. 2. Blood-gas pressures and pH were measured across the isolated lobe and compared with gas pressures in alveolar samples from the lobe. 3. When the isolated lobe was allowed to reach gaseous equilibrium with pulmonary arterial blood for 30 min, there was no significant difference between alveolar and pulmonary venous Pco2. Mean values of whole-blood base excess were similar in pulmonary arterial and pulmonary venous blood. 4. After injection of 20 ml of 8·4% sodium bicarbonate solution into a peripheral vein, Pco2, pH and plasma bicarbonate concentrations rose in the mixed venous blood. There was no change of whole-blood base excess across the lung, indicating that HCO−3, as distinct from dissolved CO2, did not enter lung tissue in measurable amounts. 5. No systematic alveolar—pulmonary venous Pco2 differences were demonstrated in this preparation other than those explicable by maldistribution of lobar blood flow.

Adaptors and Innovators: Selection versus Induction

1991 ◽  
Vol 68 (3_suppl) ◽  
pp. 1283-1290 ◽  
Author(s):  
P. A. Holland ◽  
I. Bowskill ◽  
A. Bailey
Keyword(s):  
Cognitive Style ◽  
Past Research ◽  
Significant Shift ◽  
Occupational Groups ◽  
Significant Difference ◽  
The Mean ◽  
New Entrants ◽  
Innovative Cognitive Style ◽  
Over Time ◽  
Established Group

The hypothesis that predictable differences would exist between the mean cognitive style of new entrants and those of the longer serving “established” employees in certain departments while not in others was tested. Data from 99 employees from four departments of a large British pharmaceuticals company who completed the Kirton Adaption-Innovation Inventory provided results broadly in line with the expectations of adaption-innovation theory and past research. The mean innovative cognitive style of new entrants to adaptive departments regressed towards the mean of the establishment and the occupational mean over time. In departments where there was no initial significant difference between the mean cognitive style of the new entrants and the established group, no significant shift was shown over time. Implications of these findings are suggested. The data also indicated norms for two occupational groups where previously they did not exist.

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