scholarly journals Apixaban concentration variability and relation to clinical outcomes in real-life patients with atrial fibrillation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alenka Mavri ◽  
Nina Vene ◽  
Mojca Božič-Mijovski ◽  
Marko Miklič ◽  
Lisbeth Söderblom ◽  
...  

AbstractIn some clinical situations, measurements of anticoagulant effect of apixaban may be needed. We investigated the inter- and intra-individual apixaban variability in patients with atrial fibrillation and correlated these results with clinical outcome. We included 62 patients receiving either 5 mg (A5, n = 32) or 2.5 mg (A2.5, n = 30) apixaban twice-daily. We collected three trough and three peak blood samples 6–8 weeks apart. Apixaban concentration was measured by liquid chromatography-tandem mass-spectrometry (LC–MS/MS) and by anti-Xa. Patients on A2.5 were older, had lower creatinine clearance, higher CHA2DS2VASc (4.7 ± 1.0 vs. 3.4 ± 1.7) and lower trough (85 ± 39 vs. 117 ± 53 ng/mL) and peak (170 ± 56 vs. 256 ± 91 ng/mL) apixaban concentrations than patients on A5 (all p < 0.01). In patients on A5, LC–MS/MS showed a significant difference between through levels and between peak levels (p < 0.01). During apixaban treatment, 21 patients suffered bleeding (2 major). There was no association between bleeding and apixaban concentrations or variability. Four patients who suffered thromboembolic event had lower peak apixaban concentrations than patients without it (159 ± 13 vs. 238 ± 88 ng/mL, p = 0.05). We concluded, that there was a significant intra- and inter-individual variability in apixaban trough and peak concentrations. Neither variability nor apixaban concentrations were associated with clinical outcomes.

Author(s):  
Samy Zaky ◽  
Hossam Hosny ◽  
Gehan Elassal ◽  
Noha Asem ◽  
Amin Abdel Baki ◽  
...  

Abstract Background Knowledge about the outcome of COVID-19 on pregnant women is so important. The published literature on the outcomes of pregnant women with COVID-19 is confusing. The aim of this study was to report our clinical experience about the effect of COVID-19 on pregnant women and to determine whether it was associated with increased mortality or an increase in the need for mechanical ventilation in this special category of patients. Methods This was a cohort study from some isolation hospitals of the Ministry of Health and Population, in eleven governorates, Egypt. The clinical data from the first 64 pregnant women with COVID-19 whose care was managed at some of the Egyptian hospitals from 14 March to 14 June 2020 as well as 114 non-pregnant women with COVID-19 was reviewed. Results The two groups did not show any significant difference regarding the main outcomes of the disease. Two cases in each group needed mechanical ventilation (p 0.617). Three cases (4.7%) died among the pregnant women and two (1.8%) died among the non-pregnant women (p 0.352). Conclusions The main clinical outcomes of COVID-19 were not different between pregnant and non-pregnant women with COVID-19. Based on our findings, pregnancy did not exacerbate the course or mortality of COVID-19 pneumonia.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
KOSUKE DOI ◽  
Yasuhiro Hamatani ◽  
Akiko Fujino ◽  
...  

Introduction: Anemia has been reported to be associated with poor prognosis in patients with atrial fibrillation (AF). Concomitant thrombocytopenia (TP) may or may not affect the prescription of antithrombotic drugs and clinical outcomes in these patients. Methods: The Fushimi AF Registry is a community-based prospective survey of AF patients in Fushimi-ku, Kyoto. We defined TP as platelet counts less than 150,000/μL and anemia as hemoglobin less than 11 g/dL. Among 666 patients with anemia, we compared the clinical backgrounds and outcomes of those with TP (n=183) and those without (n=483). Results: Compared with patients without TP, patients with TP were more likely to have chronic kidney disease (75.4% vs. 61.8%, p=0.001), and less likely to have hypertension (58.5% vs. 67.0%, p=0.0393), and less likely to have dyslipidemia (27.3% vs. 38.3%, p=0.0079). Age, sex, body weight, CHADS 2 score, CHA 2 DS 2 -VASc score, HAS-BLED score, and previous major bleeding were comparable between the groups. Furthermore, prescription of anti-thrombotic drugs was comparable (Figure A). On Kaplan-Meier analysis, the incidence of all-cause death was higher in TP group (hazard ratio [HR] 1.52; 95% confidence interval [CI] 1.20-1.91, p<0.05) (Figure B-1). There was no significant difference in other adverse events between patients with and without TP (major bleeding: HR 1.11; 95% CI 0.41-3.31, p=0.8, hospitalization for heart failure: HR 1.11; 95% CI 0.74-1.61, p= 0.61 and stroke or systemic embolism: HR 0.91; 95% CI 0.43-1.78, p=0.80) (Figure B-2, 3, 4). Multivariate Cox proportional hazards regression analysis adjusting for potential confounders revealed that TP was an independent determinant of all-cause death (adjusted HR: 1.41, 95% CI; 1.11-1.78, p=0.006). Conclusions: Concomitant TP in AF patients with anemia did not affect the prescription of antithrombotic drugs, and was independently associated with all-cause death in the Fushimi AF Registry.


2011 ◽  
Vol 5 ◽  
pp. CMC.S6289 ◽  
Author(s):  
John Amerena ◽  
Shih-Ann Chen ◽  
Charn Sriratanasathavorn ◽  
Jeong-Gwan Cho ◽  
Huang Dejia ◽  
...  

Background The literature suggests that the prevalence of atrial fibrillation (AF) may be lower in Asian countries than in Western countries. Nevertheless, AF remains a significant public health problem in the region. The burden of AF, the experiences of previous trials and the lack of data on AF and its management in Asia Pacific highlight the need for a comprehensive prospective study of AF management. Methods The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation Asia Pacific (RecordAF-AP) is a prospective, observational survey of the management of recently diagnosed AF patients with 1-year follow-up in 8 countries across Asia Pacific. Eligible patients presenting with AF, treated or not, will be included in the registry and data will be recorded prospectively during follow-up visits at 6 and 12 months. Results RecordAF-AP will recruit more than 3000 patients. Study recruitment commenced in April 2009 and the final results anticipated at the end of 2011. Conclusions RecordAF-AP will assess the real-life management of AF patients in Asia Pacific, including a comparison of clinical outcomes in rhythm versus rate control strategies, providing much needed insight into the costs, treatment choices and clinical outcomes of AF patients in this region.


Background: Sunscreen companies recommend replacing your chemical sunscreen every year. Consumer inquiries about product integrity under excessive exposure to heat prompted the FDA to add a requirement statement to sunscreen products indicating a need to protect stored sunscreen from excessive heat and direct sun. If heat exposure indeed affects chemical sunscreen stability, then in some areas, replacement may be warranted earlier than a year. Methods: We examined real-life scenarios related to the storage of sunscreen containers inside vehicles sitting in natural sunlight to provide information about the stability of sunscreen active ingredients under real-life storage conditions. The active ingredients avobenzone, oxybenzone, homosalate, octinoxate, octisalate, and octocrylene in samples of sunscreens were examined after heat exposure over six months using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The calculated levels of each active ingredient were then compared between the non-heat exposed samples and the heat exposed samples using a paired t-test to look for decreases in active chemicals from heat exposure. Results: No important differences were seen for heat exposure in this study of 378 hours of temperatures above 37.8 °C, with an additional 292 hours of exposure to temperatures of 32.2-37.7 °C, and 3454 hours at 26.7-32.2 °C. Conclusions: This suggests such heat exposure does not result in degradation of the active ingredients of sunscreens with sun protection factors (SPF) of 30 and 50. This is important for individuals attempting to prevent sunburns and skin cancer.


PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0245667
Author(s):  
Hee Young Ju ◽  
Ji Won Lee ◽  
Hee Won Cho ◽  
Ju Kyung Hyun ◽  
Youngeun Ma ◽  
...  

Background Large inter-individual variations in drug metabolism pose a challenge in determining 6-mercaptopurine (6MP) doses. As the last product of 6MP metabolism, DNA-thioguanine nucleotide (DNA-TGN) could reflect the efficacy of 6MP, especially in patients harboring variants in the 6MP metabolism pathway. The aim of this study was to investigate the clinical significance of DNA-TGN monitoring in Korean pediatric acute lymphoblastic leukemia (ALL) patients, focusing on the NUDT15 genotype. Methods The subjects of this study were patients who underwent ALL treatment with 6MP. Tests for the NUDT15 and TPMT genotypes were performed, and prospective DNA-TGN and erythrocyte TGN samples were collected after two weeks or more of 6MP treatment. DNA-TGN was quantified using the liquid chromatography-tandem mass spectrometry method. Results A total of 471 DNA-TGN measurements in 71 patients were analyzed, which ranged from 1.0 to 903.1 fmol thioguanine/μg DNA. The 6MP intensity demonstrated a significant relationship with DNA-TGN concentration (P<0.001). Patients harboring NUDT15 variants were treated with a lower dose of 6MP (P<0.001); however, there was no significant difference in DNA-TGN concentration when compared to patients carrying wild-type NUDT15 (P = 0.261). These patients also presented higher variation in DNA-TGN levels (P = 0.002) and DNA-TGN/6MP intensity (P = 0.019) compared to patients carrying wild-type NUDT15. DNA-TGN concentration did not show a significant correlation with WBC count (P = 0.093). Conclusions Patients harboring NUDT15 variants demonstrated similar DNA-TGN concentrations even at low doses of 6MP and showed high variability in DNA-TGN. Particularly in patients with NUDT15 variants who need a reduced 6MP dose, DNA-TGN could be applied as a useful marker to monitor the therapeutic effect of 6MP.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261440
Author(s):  
Haruka Tanabe ◽  
Hitoshi Mutai ◽  
Daimei Sasayama ◽  
Hidehiko Sasamoto ◽  
Yoshimichi Miyashiro ◽  
...  

Animal experiments have consistently shown that estrogen receptor β (ERβ)-selective ligands have antidepressant and anxiolytic effects. In humans, endogenous ligands for ERβ include 5α-androstane-3β, 17β-diol (3βAdiol) and androstenediol (Δ5-diol). We determined, for the first time, the exact serum levels of 3βAdiol and Δ5-diol in young healthy volunteers using liquid chromatography–tandem mass spectrometry (LC–MS/MS). We investigated the effect of the menstrual cycle on the levels of these steroids in women; then, we performed a gender comparison. Blood samples were collected from 48 subjects: 23 women (mean age = 28.4±7.8 years) and 25 men (mean age = 31.4±7.8 years). We collected the blood samples of women at three time-points in the menstrual cycle: the early follicular phase, ovulatory or mid-cycle phase, and mid-luteal phase. A total of 92 blood samples were analyzed using LC–MS/MS. The levels of two well-studied steroids, namely dehydroepiandrosterone (DHEA) and 17β-estradiol (E2), were simultaneously measured. Depression rating scale (Hamilton Rating Scale for Depression, Beck Depression Inventory-II and Quick Inventory of Depressive Symptomatology) scores were also recorded at the time of blood sampling. Significant differences in the levels of 3βAdiol and E2 and in the depression rating scale scores were observed over the duration of the menstrual cycle of the women. The levels of 3βAdiol and Δ5-diol were significantly lower in women than in men. E2 levels were higher in women than in men, and DHEA levels did not differ significantly between men and women. Further, women had higher scores than men on the Hamilton Rating Scale for Depression. Sex differences in depressive symptoms can be explained by 3βAdiol and Δ5-diol levels, and the effect of the menstrual cycle on mood can be explained by 3βAdiol and E2 levels, not by Δ5-diol level.


2020 ◽  
Vol 44 (8) ◽  
pp. 905-914 ◽  
Author(s):  
Gunhild Heide ◽  
Gudrun Høiseth ◽  
Gerrit Middelkoop ◽  
Åse Marit Leere Øiestad

Abstract The use of designer benzodiazepines appears to be increasing in many countries, but data concerning blood concentrations are scarce, making interpretation of concentrations difficult. The aim of this study was to report blood concentrations of clonazolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam and phenazepam and to investigate the relationship between blood concentrations and impairment. The concentration data are from blood samples collected from living cases (apprehended drivers and other drug offences) and medico-legal autopsies. The blood samples were analysed for the seven designer benzodiazepines mentioned above by ultra high performance liquid chromatography–tandem mass spectrometry. Positive cases from between 1 June 2016 and 30 September 2019 were included. Blood concentrations and the conclusion from a clinical test of impairment (when available) are reported. The presented seven benzodiazepines were detected in a total of 575 cases, where 554 of these cases concerned apprehended drivers or other criminal offenders. The number of findings and the median (range) concentrations were as follows: clonazolam, n = 22, 0.0041 mg/L (0.0017–0.053 mg/L); diclazepam, n = 334, 0.0096 mg/L (0.0016–0.25 mg/L); etizolam, n = 40, 0.054 mg/L (0.015–0.30 mg/L); flualprazolam, n = 10, 0.0080 mg/L (0.0033–0.056 mg/L); flubromazepam, n = 5, 0.037 mg/L (0.0070–0.70 mg/L); flubromazolam, n = 20, 0.0056 mg/L (0.0004–0.036 mg/L); and phenazepam, n = 138, 0.022 mg/L (0.0018–0.85 mg/L). A designer benzodiazepine was the only drug detected with relevance for impairment in 25 of the 554 living cases. The physician concluded with impairment in 19 of the 25 cases. Most of the concentrations in these cases were relatively similar to or higher than the median reported concentrations. The most frequent other drugs detected were amphetamine, tetrahydrocannabinol, clonazepam and methamphetamine. The presented blood concentrations can be helpful with the interpretation of cases involving one or more of these seven benzodiazepines. The results indicate that concentrations commonly observed in forensic cases are associated with impairment.


TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e255-e262
Author(s):  
Kira MacDougall ◽  
James D. Douketis ◽  
Na Li ◽  
Nathan P. Clark ◽  
Alfonso Tafur ◽  
...  

Abstract Introduction The Perioperative Anticoagulation Use for Surgery Evaluation (PAUSE) Study assessed a standardized perioperative management strategy in patients with atrial fibrillation who were taking a direct oral anticoagulant (DOAC) and required an elective surgery or procedure. The aim of this substudy is to analyze the safety of this management strategy across different patient subgroups, according to four presurgical variables: (1) DOAC type and dose, (2) surgery/procedure bleed risk, (3) patient renal function, and (4) age. Methods Clinical outcomes analyzed included major bleeding (MB), arterial thromboembolism, any bleeding, and any thromboembolism. We used descriptive statistics to summarize clinical outcomes, where the frequency, proportion, and 95% confidence interval were reported. Fisher's exact tests were used for testing the null hypothesis of independence between the clinical outcome and patient characteristic, where the test p-values were reported. Results There were 3,007 patients with atrial fibrillation requiring perioperative DOAC management. There was no significant difference in bleeding or thromboembolic outcomes according to DOAC type/dose regimen, renal function, or patient age. The rate of MB was significantly higher with high bleed risk procedures than low bleed risk procedures in apixaban-treated patients (2.9 vs. 0.59%; p < 0.01), but not in dabigatran-treated patients (0.88 vs. 0.91%; p = 1.0) or rivaroxaban-treated patients (2.9 vs. 1.3%; p = 0.06). The risk for thromboembolism did not differ according to surgery/procedure-related bleed risk. Conclusion Our results suggest that in DOAC-treated patients who received standardized perioperative management, surgical bleed risk is an important determinant of bleeding but not thromboembolic outcomes, although this finding was not consistent across all DOACs. There were no differences in bleeding and thromboembolism according to DOAC type and dose, renal function, or age.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F T Range ◽  
D P Peters ◽  
T Zeus ◽  
S Jander ◽  
P Mueller ◽  
...  

Abstract Background Atrial fibrillation (AF) is one of the leading cardiogenic causes for embolic stroke of unknown source (ESUS). Its incidence is growing with patients' age. Detection and rule out of AF is complex and cumbersome. The best method is an implantable loop recorder (ILR). In patients elder than 60 years, incidence of AF is reported incongruently and reliable patient characteristics that can predict a low or high risk for AF are scarce. Purpose This study reports real life incidences of AF in a group of patients undergoing ILR after ESUS. It aims to depict age dependency of AF and to identify potential confounding factors. Methods In a single center study, we analysed 111 patients (age=62±13 years, nmale=65) who received an ILR in our centre following ESUS. Patient characteristics, brain imaging, hemodynamic monitoring, blood pressure, electrocardiography, holter ecg and echocardiography data from the initial hospital stay and ILR follow-up over a mean of 460 days were analysed. Primary endpoint was the recording of AF during follow-up. Results AF was detected in 23% of all patients. Patients with AF were significantly elder than those without AF (p=0.01). Incidence of AF was in Patients <60y: 14%, 60–69y: 13%, 70–79y: 45%, >80y: 67%. We observed a significant difference in AF incidence comparing patients younger and elder than 70 years (p=0.034). Both, CHADS-Vasc (p=0.036) and HATCH-scores (p=0.018) were higher in the AF group while the simple CHADS2 Score missed significance (p=0.068). PQ duration was longer in AF patients (p=0.022) and baseline heart rate at admission was lower (p=0.027). NIHSS scores were lower in the AF group at admission (2.97 vs. 4.10; p=0.049) but due to less neurological improvement in the AF group, this difference faded until dismission (1.09 vs 1.79 p=ns). Conclusions In our real life ILR group following ESUS, strongest predictor of AF was age. Pivot point rather was at 70 than at 60 years of age.


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