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Background: For patients anticoagulated with direct oral anticoagulants (DOACs) or warfarin and on aspirin (ASA) for nonvalvular atrial fibrillation and/or venous thromboembolism, it is unclear if bleeding outcomes differ. Objectives: To assess bleeding rates for ASA with DOACs vs warfarin and one another. Methods: Registry-based cohort study of patients followed by a 6-center quality improvement collaborative in Michigan using data from 2009 to 2022. The study included adults on ASA with warfarin or DOACs for atrial fibrillation and/or venous thromboembolism without a recent myocardial infarction or heart valve replacement. Results: After propensity matching by anticoagulant class, we compared 2 groups of 1467 patients followed for a median of 18.0 months. Any bleeding and nonmajor bleeding was increased with DOACs + ASA compared with warfarin + ASA (32.2 vs 27.8 and 27.1 vs 22.9 events/100 patient-years; relative risks [RRs], 1.1 and 1.2; 95% CIs, 1.1-1.2 and 1.1-1.3, respectively). After matching by drug, patients on apixaban + ASA vs warfarin + ASA had more bleeding (31.2 vs 27.8 events/100 patient-years; RR, 1.1; 95% CI, 1.0-1.2) and nonmajor bleeding but less major bleeding (3.8 vs 4.7 events/100 patient-years; RR, 0.8; 95% CI, 0.6-1.0) and emergency room visits for bleeding. Patients on rivaroxaban + ASA vs warfarin + ASA had more bleeding (39.3 vs 26.3 events/100 patient-years, RR, 1.5; 95% CI, 1.3-1.6), nonmajor bleeding, and thrombosis. Patients on apixaban + ASA vs rivaroxaban + ASA had significantly less bleeding (22.5 vs 39.3/100 patient-years; RR, 0.6; 95% CI, 0.5-0.7), nonmajor bleeding, major bleeding (2.1 vs 5.5 events/100 patient-years; RR, 0.4; 95% CI, 0.2-0.6), emergency room visits for bleeding, and thrombotic events. Conclusion: Patients on DOAC + ASA without a recent myocardial infarction or heart valve replacement had more nonmajor bleeding but otherwise similar outcomes compared with warfarin + ASA. Patients treated with rivaroxaban + ASA experienced more adverse clinical events compared with warfarin + ASA or apixaban + ASA.
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BACKGROUND: While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment. OBJECTIVES: We aimed to better characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention. METHODS: We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality-improvement process using data abstractors, from 2018 to 2022 on the number of "alerts" that are generated in response to dosing deviating from the U.S. Food and Drug Administration instructions for atrial fibrillation (AF) and venous thromboembolism (VTE). RESULTS: Among a sample of 789 to 1,022 annual AF patients and 381 to 484 annual VTE patients prescribed a DOAC in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period (2018-2022), there were 569 alerts for AF patients and 162 alerts for VTE patients. Alerts occurred more frequently during follow-up than at the time of initial prescribing in AF patients (78.2 vs. 21.8%), but more commonly at initial prescribing in VTE patients (59.9 vs. 40.1%). After initial review by quality-improvement abstractors, 19.3% of AF alerts and 14.8% of VTE alerts resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention about 75% of the time for both populations. The most common intervention was a change in DOAC dosing. CONCLUSION: This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC, particularly for patients with AF, as off-label prescribing occurs frequently during the follow-up period.
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Biometric technology is becoming increasingly prevalent in several vital applications that substitute traditional password and token authentication mechanisms. Recognition accuracy and computational cost are two important aspects that are to be considered while designing biometric authentication systems. Thermal imaging is proven to capture a unique thermal signature for a person and thus has been used in thermal face recognition. However, the literature did not thoroughly analyse the impact of feature selection on the accuracy and computational cost of face recognition which is an important aspect for limited resources applications like IoT ones. Also, the literature did not thoroughly evaluate the performance metrics of the proposed methods/solutions which are needed for the optimal configuration of the biometric authentication systems. This paper proposes a thermal face-based biometric authentication system. The proposed system comprises five phases: a) capturing the user's face with a thermal camera, b) segmenting the face region and excluding the background by optimized superpixel-based segmentation technique to extract the region of interest (ROI) of the face, c) feature extraction using wavelet and curvelet transform, d) feature selection by employing bio-inspired optimization algorithms: grey wolf optimizer (GWO), particle swarm optimization (PSO) and genetic algorithm (GA), e) the classification (user identification) performed using classifiers: random forest (RF), k-nearest neighbour (KNN), and naive bayes (NB). Upon the public dataset, Terravic Facial IR, the proposed system was evaluated using the metrics: accuracy, precision, recall, F-measure, and receiver operating characteristic (ROC) area. The results showed that the curvelet features optimized using the GWO and classified with random forest could help in authenticating users through thermal images with performance up to 99.5% which is better than the results of wavelet features by 10% while the former used 5% fewer features. In addition, the statistical analysis showed the significance of our proposed model. Compared to the related works, our system showed to be a better thermal face authentication model with a minimum set of features, making it computational-friendly.
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Identificación Biométrica , Reconocimiento Facial , Teorema de Bayes , Identificación Biométrica/métodos , Algoritmos , BiometríaRESUMEN
Eobania vermiculata is a hazardous snail that can damage ornamental plants and cause significant harm to plant sections in Egyptian areas. Herein, the molluscicidal activity of CuPb-Ferrite/TiO2 and TiO2 nanoparticles (NPs) against E. vermiculata was evaluated using the poisonous bait method. LC50 values were determined using the leaf dipping and contact methods, with values of 631.23 and 1703.49 ppm for CuPb-Ferrite/TiO2 and 193.67 and 574.97 ppm for TiO2. Exposure to both NPs resulted in a significant increase in the biochemical parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), as well as a decrease in total protein (TP) percentage of E. vermiculata. Histological examinations revealed that many digestive cells had ruptured, and their contents had been lost, while the foot's epithelial layer became ruptured. The average reduction was 66.36% for CuPb-Ferrite/TiO2 NPs compared to the recommended molluscicide, Neomyl, with a 70.23% reduction in the field application. Electrophoretic separation of total protein using sodium dodecyl sulfate-polyacrylamide gel electrophoresis after treatment with LC50 concentrations of TiO2 and CuPb-Ferrite/TiO2 demonstrated the potency of these synthetic compounds as molluscicidal agents. Therefore, we recommend the use of CuPb-Ferrite/TiO2 NPs as a novel land snail molluscicide because it is safe to use, and the baits are arranged to not affect irrigation water, with a high molluscicidal effect.
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Nanocompuestos , Titanio , Animales , Titanio/farmacología , CaracolesRESUMEN
Safety and efficacy of direct oral anticoagulants (DOAC) in low weight patients with atrial fibrillation (AF) is unclear due to few low body weight patients enrolled in clinical trials. To assess bleeding and thrombotic event rates for patients with AF that are prescribed apixaban and have a low versus normal body weight. We analyzed patients with AF prescribed apixaban from 2017 to 2020 with at least 12 months of follow-up. Patients were divided into low [< 60 kg (kg)] and normal (60-100 kg) weight cohorts. Bleeding and thrombotic event rates were compared. Poisson regression and Cox proportional hazard models were used to estimate adjusted adverse event rates. A total of 545 patients met inclusion criteria. In the unadjusted analysis, there was an increase in non-major bleeding events requiring an Emergency Department visit more often in the low versus normal weight cohort (10.8 versus 7.4 per 100 patient-years, p = 0.15). Thrombotic event rates also occurred more often in the lower versus normal weight cohort (2.4 versus 0.9 per 100 patient-years, p = 0.09). However, adjusted analysis found no statistically significant difference in bleeding or thrombotic events between low and normal weight cohorts. The adjusted hazard ratio for bleeding was similar between the two weight cohorts. The use of apixaban in low body weight patients was not associated with higher rates of bleeding or thrombotic events, compared to those with normal body weight, after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients.
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Fibrilación Atrial , Accidente Cerebrovascular , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Warfarina/uso terapéutico , Anticoagulantes/efectos adversos , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Peso Corporal Ideal , Hemorragia/inducido químicamente , Hemorragia/tratamiento farmacológico , Piridonas/efectos adversos , Delgadez/tratamiento farmacológico , Administración OralRESUMEN
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 MAQI2 (Michigan Anticoagulation Quality Improvement Initiative) registry who were receiving anticoagulation for a provoked VTE. The MAQI2 registry comprises 6 centers in Michigan that manage patients' 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 >120 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.
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Tromboembolia Venosa , Humanos , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/inducido químicamente , Warfarina , Estudios Retrospectivos , Anticoagulantes/uso terapéutico , Factores de RiesgoRESUMEN
Importance: For some patients receiving warfarin, adding aspirin (acetylsalicylic acid) increases bleeding risk with unclear treatment benefit. Reducing excess aspirin use could be associated with improved clinical outcomes. Objective: To assess changes in aspirin use, bleeding, and thrombosis event rates among patients treated with warfarin. Design, Setting, and Participants: This pre-post observational quality improvement study was conducted from January 1, 2010, to December 31, 2019, at a 6-center quality improvement collaborative in Michigan among 6738 adults taking warfarin for atrial fibrillation and/or venous thromboembolism without an apparent indication for concomitant aspirin. Statistical analysis was conducted from November 26, 2020, to June 14, 2021. Intervention: Primary care professionals for patients taking aspirin were asked whether an ongoing combination aspirin and warfarin treatment was indicated. If not, then aspirin was discontinued with the approval of the managing clinician. Main Outcomes and Measures: Outcomes were assessed before and after intervention for the primary analysis and before and after 24 months before the intervention (when rates of aspirin use first began to decrease) for the secondary analysis. Outcomes included the rate of aspirin use, bleeding, and thrombotic outcomes. An interrupted time series analysis assessed cumulative monthly event rates over time. Results: A total of 6738 patients treated with warfarin (3160 men [46.9%]; mean [SD] age, 62.8 [16.2] years) were followed up for a median of 6.7 months (IQR, 3.2-19.3 months). Aspirin use decreased slightly from a baseline mean use of 29.4% (95% CI, 28.9%-29.9%) to 27.1% (95% CI, 26.1%-28.0%) during the 24 months before the intervention (P < .001 for slope before and after 24 months before the intervention) with an accelerated decrease after the intervention (mean aspirin use, 15.7%; 95% CI, 14.8%-16.8%; P = .001 for slope before and after intervention). In the primary analysis, the intervention was associated with a significant decrease in major bleeding events per month (preintervention, 0.31%; 95% CI, 0.27%-0.34%; postintervention, 0.21%; 95% CI, 0.14%-0.28%; P = .03 for difference in slope before and after intervention). No change was observed in mean percentage of patients having a thrombotic event from before to after the intervention (0.21% vs 0.24%; P = .34 for difference in slope). In the secondary analysis, reducing aspirin use (starting 24 months before the intervention) was associated with decreases in mean percentage of patients having any bleeding event (2.3% vs 1.5%; P = .02 for change in slope before and after 24 months before the intervention), mean percentage of patients having a major bleeding event (0.31% vs 0.25%; P = .001 for change in slope before and after 24 months before the intervention), and mean percentage of patients with an emergency department visit for bleeding (0.99% vs 0.67%; P = .04 for change in slope before and after 24 months before the intervention), with no change in mean percentage of patients with a thrombotic event (0.20% vs 0.23%; P = .36 for change in slope before and after 24 months before the intervention). Conclusions and Relevance: This quality improvement intervention was associated with an acceleration of a preexisting decrease in aspirin use among patients taking warfarin for atrial fibrillation and/or venous thromboembolism without a clear indication for aspirin therapy. Reductions in aspirin use were associated with reduced bleeding. This study suggests that an anticoagulation clinic-based aspirin deimplementation intervention can improve guideline-concordant aspirin use.
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Fibrilación Atrial , Tromboembolia Venosa , Adulto , Anticoagulantes/efectos adversos , Aspirina , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/inducido químicamente , Hemorragia/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/prevención & control , Warfarina/efectos adversosRESUMEN
BACKGROUND: Urothelial carcinoma (UC) is the most common type of bladder cancer. Glucose transporter 4 (GLUT4) is one of glucose transporter proteins' family which facilitates glucose transport inside the cells. It was found to be overexpressed in several malignant tumors. Cancer-associated fibroblasts (CAFs) are heterogeneous stromal cells located adjacent to cancer cells and are considered one of the most important tumor stromal cells. They have been associated with enhancing tumor growth and invasion. GLUT4 expression in malignant epithelial cells and fibroblast activation protein (FAP) expression in CAFs of UC in relation to angiogenesis and clinicopathological characteristics are studied in this work. MATERIALS AND METHODS: The study was carried out on 72 paraffin blocks of UC (27 radical cystectomies and 45 transurethral resections). Immunohistochemical staining was performed with GLUT4, FAP, and CD34 antibodies. Expression of GLUT4 and FAP was classified according to the staining intensities and percentages into low and high groups. CD34-stained microvessels' mean count in five microscopic fields (×200) was taken as the microvessel density (MVD). RESULTS: GLUT4 overexpression was detected in 32 UC. It was significantly associated with high-grade tumors, advanced primary tumor (pT) stage, lymphovascular invasion (LVI), and regional lymph node invasion. High FAP expression was appreciated in 27 UC and was significantly linked to LVI and advanced TNM staging. Intratumor MVD significantly increased in UC with muscle invasion, LVI, and regional lymph node and/or distant metastasis. A significant positive correlation between GLUT4, FAP expression, and MVD was found. CONCLUSION: GLUT4 and FAP expression was significantly associated with increased intratumor MVD and adverse clinicopathological factors.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/metabolismo , Glucosa , Proteínas Facilitadoras del Transporte de la Glucosa , Humanos , Neovascularización Patológica/genética , Neovascularización Patológica/patología , Parafina , Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
BACKGROUND: Differences in clinical outcomes following a temporary interruption of warfarin or a direct oral anticoagulant (DOAC) for a surgical procedure are not well described. Differences in patient characteristics from practice-based cohorts have not typically been accounted for in prior analyses. AIM: To describe risk-adjusted differences in postoperative outcomes following an interruption of warfarin vs DOACs. METHODS: Patients receiving care at six anticoagulation clinics participating in the Michigan Anticoagulation Quality Improvement Initiative were included if they had at least one oral anticoagulant interruption for a procedure. Inverse probability of treatment weighting (IPTW) was used to balance baseline differences between the warfarin cohort and DOAC cohort. Bleeding and thromboembolic events within 30 days following the procedure were compared between the IPTW cohorts using the Poisson distribution test. RESULTS: A total of 525 DOAC patients were matched with 1323 warfarin patients, of which 923 were nonbridged warfarin patients and 400 were bridged warfarin patients. The occurrence of postoperative minor bleeding (10.8% vs. 4.7%, p < .001), major bleeding (2.9% vs. 1.1%, p = .01) and clinically relevant nonmajor bleeding (CRNMB) (6.5% vs. 3.0%, p = .002) was greater in the DOAC cohort compared with the nonbridged warfarin cohort. The rates of postoperative bleeding outcomes were similar between the DOAC and the bridged warfarin cohorts. CONCLUSION: Perioperative interruption of DOACs, compared with warfarin without bridging, is associated with a higher incidence of 30-day minor bleeds, major bleeds, and CRNMBs. Further research investigating the perioperative outcomes of these two classes of anticoagulants is warranted.
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Fibrilación Atrial , Warfarina , Humanos , Warfarina/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Estudios Retrospectivos , Anticoagulantes/efectos adversos , Hemorragia Posoperatoria/inducido químicamente , Administración OralRESUMEN
The glass clover snail, Monacha cartusiana (M. cartusiana) is one of the most seriously impacting economic animal pests spreading across Egypt which inflicts severe damages to the agriculture. A green route is developed by deploying an abundant Rosemary plant leaves aqueous extract to synthesize ZnO and F-doped ZnO (F-ZnO) nanoparticles (NPs) that display high molluscicidal activities against the M. cartusiana land snails via leaf dipping and contact techniques. The effect of lethal concentrations, that kills 50% of exposed snails (LC50) value of the treatments, is examined on the activity of alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), enzymes, total protein (TP), total lipids (TL) and cholesterol level of snails, including the histopathological evaluation of the digestive gland and foot of M. Cartusiana. Their molluscicidal activity as poisonous baits under field conditions is also evaluated and compared to the recommended molluscicide, Neomyl. The results show that F- doping dramatically improves the snail control capability of ZnO NPs, and promotes a considerable increase in both ALT and AST enzymes with an enhancement of TL and Cholesterol levels, but a significant decrease in TP content and ALP activity in treated snails compared to the control group. The LC50 values are found to be 1381.55 and 2197.59 ppm using the leaf dipping for F-ZnO and ZnO, while 237.51 and 245.90 ppm can be achieved using the contact technique, respectively. The greenly synthesized F-ZnO and ZnO NPs induce severe histological alterations in the digestive gland and foot of M. cartusiana, including a complete destruction of the digestive tubules. The histological evaluation of the foot of M. cartusiana exposed to ZnO, shows a rupture of the epithelial layer of the foot sole, while F- ZnO NPs causes the folds of the foot becoming deeper and the rupture of epithelial layer. Our field experiments further demonstrate that F-ZnO achieves 60.08% reduction, while ZnO attains 56.39% diminution in snail population compared to the commercial, Neomyl (69.55%), exhibiting great potentials in controlling the harmful land snail populations.
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Moluscocidas , Óxido de Zinc , Animales , Colesterol , Dosificación Letal Mediana , Moluscocidas/toxicidad , Extractos Vegetales/química , Hojas de la Planta , Óxido de Zinc/toxicidadRESUMEN
Patients' international normalized ratios (INRs) often fall slightly out of range. In these cases, the American College of Chest Physicians (ACCP) guidelines suggest maintaining the current warfarin dose and retesting the INR within the following 2 weeks (watchful waiting). We sought to determine whether watchful waiting or dose changes for slightly out-of-range INRs is more effective in obtaining in-range INRs at follow-up. INRs and management strategies of warfarin-treated patients within the Michigan Anticoagulation Quality Improvement Initiative registry were analyzed. Management strategies included watchful waiting or dose changes. INRs slightly out of range (target range 2.0-3.0) and their associated management were identified. Multilevel mixed-effects logistic regression was used to estimate the probability of the next INR being in range, adjusted for clustering due to multiple out-of-range INRs per patient. A total of 45 351 slightly out-of-range INRs (ranging 1.50-1.99 and 3.01-3.49) from 8288 patients were identified. The next INR was slightly less likely to be in range with watchful waiting than with a dose change (predicted probabilities 58.9% vs 60.0%, P = 0.024). Although a significant statistical difference was detected in the probabilities of the next INR being back in range when managed by a dose change compared with watchful waiting following a slightly out-of-range INR, the magnitude of the difference was small and unlikely to represent clinical importance. Our study supports the current guideline recommendations for watchful waiting in cases of slightly out-of-range INRs values.
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Anticoagulantes , Warfarina , Anticoagulantes/uso terapéutico , Humanos , Relación Normalizada Internacional , Warfarina/uso terapéutico , Espera VigilanteRESUMEN
Current guidelines recommend targeting an international normalized ratio (INR) of 2.5 to 3.5 for patients with mechanical aortic valve replacement (AVR) and additional risk factors for thromboembolic events. Available literature supporting the higher intensity (INR) goal is lacking. We aimed to evaluate the association of standard and higher intensity anticoagulation on outcomes in this patient population. The Michigan Anticoagulation Quality Improvement Initiative database was used to identify patients with mechanical AVR and at least one additional risk factor. Patients were classified into 2 groups based on INR goal: standard-intensity (INR goal 2.5) or higher-intensity (INR goal 3.0). Cox-proportional hazard model was used to calculate adjusted hazard ratios. One hundred and forty-six patients were identified of whom 110 (75.3%) received standard-intensity anticoagulation and 36 (24.7%) received higher intensity anticoagulation. Standard-intensity patients were older and more likely to be on aspirin. Atrial fibrillation was the most common additional risk factor for inclusion. The primary outcome of thromboembolic events, bleeding, or all-cause death was 13.9 and 19.5/100-person-years in the standard-intensity and higher intensity groups, respectively (adjusted HR 2.58, 95% confidence interval 1.28 to 5.18). Higher-intensity anticoagulation was significantly associated with any bleeding (adjusted HR 2.52, 95% confidence interval 1.27 to 5.00) and there were few thromboembolic events across both groups (5 events total). These results challenge current guideline recommendations for anticoagulation management of mechanical AVR in patients with additional risk factors.
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Anticoagulantes/administración & dosificación , Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas , Tromboembolia/epidemiología , Tromboembolia/prevención & control , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos , Medición de Riesgo , Factores de RiesgoRESUMEN
Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes. Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE). Design, Setting, and Participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up. Exposures: Use of ASA concomitant with DOAC therapy. Main Outcomes and Measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death. Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02). Conclusion and Relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.
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Anticoagulantes/efectos adversos , Aspirina/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Hemorragia/inducido químicamente , Tromboembolia Venosa/tratamiento farmacológico , Anticoagulantes/uso terapéutico , Aspirina/uso terapéutico , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Masculino , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Piridinas/efectos adversos , Piridinas/uso terapéutico , Piridonas/efectos adversos , Piridonas/uso terapéutico , Sistema de Registros , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Tiazoles/efectos adversos , Tiazoles/uso terapéuticoRESUMEN
IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.
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Anafilaxia/inducido químicamente , Anticoagulantes/efectos adversos , Autoanticuerpos/sangre , Autoantígenos/inmunología , Plaquetas/metabolismo , Heparina/efectos adversos , Técnicas para Inmunoenzimas/métodos , Inmunoglobulina G/sangre , Activación Plaquetaria/inmunología , Factor Plaquetario 4/inmunología , Serotonina/sangre , Trombocitopenia/diagnóstico , Adulto , Anticoagulantes/uso terapéutico , Autoanticuerpos/inmunología , Quimioterapia Combinada , Reacciones Falso Negativas , Femenino , Paro Cardíaco , Heparina/uso terapéutico , Humanos , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Errores Médicos , Obesidad/complicaciones , Embolia Pulmonar/complicaciones , Embolia Pulmonar/tratamiento farmacológico , Recurrencia , Sensibilidad y Especificidad , Trombocitopenia/inducido químicamente , Trombosis de la Vena/complicaciones , Trombosis de la Vena/tratamiento farmacológico , Warfarina/uso terapéuticoRESUMEN
BACKGROUND: Use of bridging anticoagulation increases a patient's bleeding risk without clear evidence of thrombotic prevention among warfarin-treated patients with atrial fibrillation. Contemporary use of bridging anticoagulation among warfarin-treated patients with venous thromboembolism (VTE) has not been studied. METHODS: We identified warfarin-treated patients with VTE who temporarily stopped warfarin for a surgical procedure between 2010 and 2018 at six health systems. Using the 2012 American College of Chest Physicians guideline, we assessed use of periprocedural bridging anticoagulation based on recurrent VTE risk. Recurrent VTE risk and 30-day outcomes (bleeding, thromboembolism, emergency department visit) were each assessed using logistic regression adjusted for multiple procedures per patient. RESULTS: During the study period, 789 warfarin-treated patients with VTE underwent 1529 procedures (median, 2; interquartile range, 1-4). Unadjusted use of bridging anticoagulation was more common in patients at high risk for VTE recurrence (99/171, 57.9%) than for patients at moderate (515/1078, 47.8%) or low risk of recurrence (134/280, 47.86%). Bridging anticoagulation use was higher in high-risk patients compared with low- or moderate-risk patients in both unadjusted (P = .013) and patient-level cluster-adjusted analyses (P = .031). Adherence to American College of Chest Physicians guidelines in high- and low-risk patients did not change during the study period (odds ratio, 0.98 per year; 95% confidence interval, 0.91-1.05). Adverse events were rare and not statistically different between the two treatment groups. CONCLUSIONS: Bridging anticoagulation was commonly overused among low-risk patients and underused among high-risk patients treated with warfarin for VTE. Adverse events were rare and not different between the two treatment groups.
Asunto(s)
Tromboembolia Venosa , Anticoagulantes/efectos adversos , Estudios de Cohortes , Heparina de Bajo-Peso-Molecular , Humanos , Sistema de Registros , Factores de Riesgo , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
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: < 1 creatinine level/year for patients with CrCl > 50, or < 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 > 50, 11.5% had < 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received < 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.
Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Creatinina/sangre , Monitoreo de Drogas/métodos , Inhibidores del Factor Xa/uso terapéutico , Anciano , Fibrilación Atrial/complicaciones , Creatinina/farmacocinética , Monitoreo de Drogas/normas , Inhibidores del Factor Xa/efectos adversos , Femenino , Humanos , Enfermedades Renales/complicaciones , Masculino , Michigan , Persona de Mediana Edad , Estudios Retrospectivos , Accidente Cerebrovascular/prevención & controlRESUMEN
In the last few decades, several growth factors were identified in the testis of various mammalian species. Growth factors are shown to promote cell proliferation, regulate tissue differentiation, and modulate organogenesis. In the present investigation we have studied the localization of EGF and EGFR in the adult bovine testis by means of immunohistochemical method. Our results demonstrated that EGF and EGFR were localized solely to the bovine testicular germ cells (spermatogonia, spermatocytes, and round spermatids). In contrast, the somatic testicular cells (i.e., Sertoli, Leydig, and myofibroblast cells) exhibited no staining affinity. EGF and EGFR were additionally detected in the epithelial lining of straight tubules and rete testis. Interestingly, the distribution of EGF and EGFR in the germ cells was mainly dependent upon the cycle of the seminiferous epithelium since their localization appeared to be preponderant during the spermatogonia proliferation and during the meiotic and spermiogenic processes. In conclusion, such findings may suggest that EGF and EGFR are important paracrine and/or autocrine regulators of spermatogenesis in bovine.