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INTRODUCTION: Combat medics who are responsible for the care of injured warfighters face challenges from their reliance on medical alarms that exceed the noise levels recommended by the WHO. This is because the elevated noise levels in military facilities, particularly from vehicular units and weaponry, compromise the combat medics' effectiveness and attentiveness to medical alarms. We previously designed a graphical ("configural") display to communicate patients' vital signs and found that when the configural display and traditional numerical display were concurrently presented to participants, it produced the fastest identification of patient vital signs and triggered the fewest number of alarms. This study used eye tracking to assess how participants direct visual attention to and engage with concurrently presented numerical and configural vital sign displays. MATERIALS AND METHODS: We recruited 30 undergraduate students with normal hearing and vision for this study. Subjects were tasked with monitoring a simulated patient's vital signals using simultaneously presented numerical and configural vital sign displays. Concurrently, they performed an N-back task to simulate the multitasking required in a military environment. We manipulated the eccentricity and display position of the numerical and configural displays through 4 orientations, with each orientation being used in a monitoring block lasting 12 minutes. Continuous eye tracking was utilized to collect physiological data about participant display preference. RESULTS: We used eye tracking to analyze several metrics: Total display viewing time, total viewing time percentage, number of dwells (groups of eye fixations), mean fixations per dwell, and fixation patterns during an emergency event. Participants spent more time looking at the configural display than the numerical display during nominal monitoring and emergency events. During emergencies, the percentage of time individuals spent looking at the configural display increased from 30 to 50%, while there was no corresponding increase in the participants' looking at the numerical display. When there were 2 concurrent emergency events instead of 1, total viewing time did not increase, suggesting that participants did not need to change their viewing strategy when the emergency situation complexity increased. Also, during emergencies, participants directed nearly half of their fixations to the configural display during the first 2 seconds of an emergency, while only directing fewer than 5% of fixations to the numerical display during that same period. The average response time for an emergency event was around 2 seconds, which suggests that participants obtained relevant information from the configural display in this time period. CONCLUSIONS: We found that when a patient monitor contains both a configural display and a numerical display, participants look at the configural display. Furthermore, during time-sensitive situations, participants utilize the configural display to provide important information. We suggest this because the configural display integrates the relevant vital signs into one display. These findings provide justification for pursuing integrated vital sign displays to efficiently communicate patient conditions in complex environments. On the battlefield, swift decision-making is essential, as combat medics must minimize the time required to assess and act in critical situations.
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Médicos de Combate , Monitorização Fisiológica , Humanos , Tecnologia de Rastreamento Ocular/instrumentação , Monitorização Fisiológica/métodos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/estatística & dados numéricosRESUMO
The form and function of biomolecular condensates are intimately linked to their material properties. Here, we integrate microrheology with molecular simulations to dissect the physical determinants of condensate fluid phase dynamics. By quantifying the timescales and energetics of network relaxation in a series of heterotypic viscoelastic condensates, we uncover distinctive roles of sticker motifs, binding energy, and chain length in dictating condensate dynamical properties. We find that the mechanical relaxation times of condensate-spanning networks are determined by both intermolecular interactions and chain length. We demonstrate, however, that the energy barrier for network reconfiguration, termed flow activation energy, is independent of chain length and only varies with the strengths of intermolecular interactions. Biomolecular diffusion in the dense phase depends on a complex interplay between viscoelasticity and flow activation energy. Our results illuminate distinctive roles of chain length and sequence-specific multivalent interactions underlying the complex material and transport properties of biomolecular condensates.
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Condensados Biomoleculares , Hidrodinâmica , Fenômenos Físicos , Difusão , Exame FísicoRESUMO
The enhancement in responsivity of photodiodes (PDs) or avalanche photodiodes (APDs) with the traditional flip-chip bonding package usually comes at the expense of degradation in the optical-to-electrical (O-E) bandwidth due to the increase of parasitic capacitance. In this work, we demonstrate backside-illuminated In0.52Al0.48As based APDs with novel flip-chip bonding packaging designed to relax this fundamental trade-off. The inductance induced peak in the measured O-E frequency response of these well-designed and well-packaged APDs, which can be observed around its 3-dB bandwidth (â¼30â GHz), effectively widens the bandwidth and becomes more pronounced when the active diameter of the APD is aggressively downscaled to as small as 3â µm. With a typical active window diameter of 14â µm, large enough for alignment tolerance and low optical coupling loss, the packaged APD exhibits a moderate damping O-E frequency response with a bandwidth (36 vs. 31â GHz) and responsivity (3.4 vs. 2.3 A/W) superior to those of top-illuminated reference sample under 0.9 Vbr operation, to attain a high millimeter wave output power (0 dBm at 40â GHz) and output current (12.5â mA at +8.8 dBm optical power). The excellent static and dynamic performance of this design open up new possibilities to further improve the sensitivity at the receiver-end of the next-generation of passive optical network (PON) and coherent communication systems.
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Auditory roughness in medical alarm sounds is an important design attribute, and has been shown to impact user performance and perception. While roughness can assist in decreased signal-to-noise ratios (perceived loudness) and communicate urgency, it might also impact patient recovery. Therefore, considerations of neuroscience correlates, music theory, and patient impact are critical aspects to investigate in order to optimise alarm design.
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Alarmes Clínicos , Som , Humanos , Monitorização FisiológicaRESUMO
Zinc is an essential minor element for rice growth and human health, which can also change the structure of the microorganisms. However, it remains unclear for the effects of zinc fertilizer on microbiome function in agricultural soils and crops. To solve this research gap, we investigated the relationship between improving rice (Oryza sativa L.) yield, Zn concentration, soil microbial community diversity, and function by the application of Zn fertilizer. The field trials included three rice varieties (Huanghuazhan, Nanjing9108, and Nuodao-9925) and two soil Zn levels (0 and 30 kg ha-1) in Jiangsu province, China. As a test, we studied the variety of soil bacterial composition, diversity, and function using 16S rRNA gene sequencing. The results showed that soil Zn application reduced the diversity of microbial community, but the bacterial network was more closely linked, and the metabolic function of bacterial community was improved, which increased the grain yield (17.34-19.52%) and enriched the Zn content of polished rice (1.40-20.05%). Specifically, redundancy analysis (RDA) and Mantel's test results revealed soil total nitrogen (TN) was the primary driver that led to a community shift in the rice rhizosphere bacterial community, and soil organic carbon (SOC) was considered to have a strong influence on dominant phyla. Furthermore, network analysis indicated the most critical bacterial taxa were identified as Actinobacteria, Bacteroidetes, Proteobacteria, and Chloroflexi based on their topological roles of microorganisms. KEGG metabolic pathway prediction demonstrated that soil Zn application significantly (p < 0.05) improved lipid metabolism, amino acid metabolism, carbohydrate metabolism, and xenobiotic biodegradation. Overall, their positive effects were different among rice varieties, of which Nanjing-9108 (NJ9108) performed better. This study opens new avenues to deeply understand the plant and soil-microbe interactions by the application of fertilizer and further navigates the development of Zn-rich rice cultivation strategies.
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We consider the use of AI techniques to expand the coverage, access, and equity of urban data. We aim to enable holistic research on city dynamics, steering AI research attention away from profit-oriented, societally harmful applications (e.g., facial recognition) and toward foundational questions in mobility, participatory governance, and justice. By making available high-quality, multi-variate, cross-scale data for research, we aim to link the macrostudy of cities as complex systems with the reductionist view of cities as an assembly of independent prediction tasks. We identify four research areas in AI for cities as key enablers: interpolation and extrapolation of spatiotemporal data, using NLP techniques to model speech- and text-intensive governance activities, exploiting ontology modeling in learning tasks, and understanding the interaction of fairness and interpretability in sensitive contexts.
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The compartment niche is the main reason behind the shifts in endophytic bacterial communities. Long-term organic greenhouse exerted limited influence on the variations of endophytic bacterial communities. Organic greenhouse and root had more complex co-occurrence networks than conventional greenhouse and stem, respectively. Cultivable method results found that Protecbacteria, Bacteriodes, and Actinobacteria are the dominant phyla in the endophytes.
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A challenge to improve an integrative phenotype, like yield, is the interaction between the broad range of possible molecular and physiological traits that contribute to yield and the multitude of potential environmental conditions in which they are expressed. This study collected data on 31 phenotypic traits, 83 annotated metabolites, and nearly 22,000 transcripts from a set of 57 diverse, commercially relevant maize hybrids across three years in central U.S. Corn Belt environments. Although variability in characteristics created a complex picture of how traits interact produce yield, phenotypic traits and gene expression were more consistent across environments, while metabolite levels showed low repeatability. Phenology traits, such as green leaf number and grain moisture and whole plant nitrogen content showed the most consistent correlation with yield. A machine learning predictive analysis of phenotypic traits revealed that ear traits, phenology, and root traits were most important to predicting yield. Analysis suggested little correlation between biomass traits and yield, suggesting there is more of a sink limitation to yield under the conditions studied here. This work suggests that continued improvement of maize yields requires a strong understanding of baseline variation of plant characteristics across commercially-relevant germplasm to drive strategies for consistently improving yield.
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Zea mays/genética , Biomassa , Produção Agrícola , Meio Ambiente , Regulação da Expressão Gênica de Plantas/genética , Estudos de Associação Genética , Fenótipo , Reguladores de Crescimento de Plantas/metabolismo , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/crescimento & desenvolvimento , Característica Quantitativa Herdável , Zea mays/anatomia & histologia , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismoRESUMO
Cu doping of ZnTe, which is an important semiconductor for various optoelectronic applications, has been successfully achieved previously by several techniques. However, besides its electrical transport characteristics, other physical and chemical properties of heavily Cu-doped ZnTe have not been reported. We found an interesting self-assembled formation of crystalline well-aligned Cu-Te nano-rods near the surface of heavily Cu-doped ZnTe thin films grown via the molecular beam epitaxy technique. A phenomenological growth model is presented based on the observed crystallographic morphology and measured chemical composition of the nano-rods using various imaging and chemical analysis techniques. When substitutional doping reaches its limit, the extra Cu atoms favor an up-migration toward the surface, leading to a one-dimensional surface modulation and formation of Cu-Te nano-rods, which explain unusual observations on the reflection high energy electron diffraction patterns and apparent resistivity of these thin films. This study provides an insight into some unexpected chemical reactions involved in the heavily Cu-doped ZnTe thin films, which may be applied to other material systems that contain a dopant having strong reactivity with the host matrix.
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Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Benzimidazóis/administração & dosagem , Varfarina/administração & dosagem , beta-Alanina/análogos & derivados , Feminino , Humanos , MasculinoRESUMO
Significant multiplexing capacity of optical time-domain coding has been recently demonstrated by tuning luminescence lifetimes of the upconversion nanoparticles called 'τ-Dots'. It provides a large dynamic range of lifetimes from microseconds to milliseconds, which allows creating large libraries of nanotags/microcarriers. However, a robust approach is required to rapidly and accurately measure the luminescence lifetimes from the relatively slow-decaying signals. Here we show a fast algorithm suitable for the microsecond region with precision closely approaching the theoretical limit and compatible with the rapid scanning cytometry technique. We exploit this approach to further extend optical time-domain multiplexing to the downconversion luminescence, using luminescence microspheres wherein lifetimes are tuned through luminescence resonance energy transfer. We demonstrate real-time discrimination of these microspheres in the rapid scanning cytometry, and apply them to the multiplexed probing of pathogen DNA strands. Our results indicate that tunable luminescence lifetimes have considerable potential in high-throughput analytical sciences.
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Elementos da Série dos Lantanídeos/química , Algoritmos , LuminescênciaRESUMO
The sensitivity of filter-based fluorescence microscopy techniques is limited by autofluorescence background. Time-gated detection is a practical way to suppress autofluorescence, enabling higher contrast and improved sensitivity. In the past few years, three groups of authors have demonstrated independent approaches to build robust versions of time-gated luminescence microscopes. Three detailed, step-by-step protocols are provided here for modifying standard fluorescent microscopes to permit imaging time-gated luminescence.
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Luminescência , Microscopia/instrumentação , Calibragem , Emulsões , Microesferas , Óleos , Processamento de Sinais Assistido por Computador , ÁguaRESUMO
It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA2DS2-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Eletrocardiografia/métodos , Hipertrofia Ventricular Esquerda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/mortalidade , Feminino , Humanos , Hipertrofia Ventricular Esquerda/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Prevalência , Prognóstico , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Análise de SobrevidaRESUMO
BACKGROUND: Atrial fibrillation is associated with increased mortality, but the specific causes of death and their predictors have not been described among patients on effective anticoagulant therapy. METHODS AND RESULTS: The Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial randomized 18 113 patients (age, 71.5 ± 9 years; male, 64%; CHADS2 score, 2.1 ± 1) to receive dabigatran or warfarin. Median follow-up was 2 years, and complete follow-up was achieved in 99.9% of patients. All deaths were categorized by the investigators using prespecified definitions followed by central adjudication. Overall, 1371 deaths occurred (annual mortality rate, 3.84%; 95% confidence interval [CI], 3.64-4.05). Cardiac deaths (sudden cardiac death and progressive heart failure) accounted for 37.4% of all deaths, whereas stroke- and hemorrhage-related deaths represented 9.8% of the total mortality. An examination of the causes of death according to dabigatran or warfarin showed that dabigatran significantly reduced vascular (embolism and hemorrhage-related) mortality (relative risk, 0.63; 95% CI, 0.45-0.88; P=0.007), whereas other causes of death were similar between treatments, including cardiac mortality (relative risk, 0.96; 95% CI, 0.80-1.15; P=0.638). The two strongest independent predictors of cardiac death in this population were heart failure (hazard ratio, 3.02; 95% CI, 2.45-3.73; P<0.0001), and prior myocardial infarction (hazard ratio, 2.05; 95% CI, 1.61-2.62; P<0.0001). CONCLUSIONS: The majority of deaths are not related to stroke in a contemporary anticoagulated atrial fibrillation population. These results emphasize the need to identify interventions beyond effective anticoagulation to further reduce mortality in atrial fibrillation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
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Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Benzimidazóis/administração & dosagem , Varfarina/administração & dosagem , beta-Alanina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Dabigatrana , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , beta-Alanina/administração & dosagemRESUMO
OBJECTIVES: This study sought to compare the net clinical benefit of dabigatran 110 mg bid and 150 mg bid with that of warfarin in patients with atrial fibrillation (AF). BACKGROUND: In patients with AF, dabigatran 110 mg bid and 150 mg bid are associated with similar rates of death. However, the higher dose reduces ischemic stroke and increases bleeding compared with the lower dose. Therefore, there is uncertainty about how to evaluate the overall benefit of the 2 doses. METHODS: In 18,113 AF patients in the RE-LY (Randomized Evaluation of Long Term Anticoagulant Therapy) trial, we used a previously developed method for integrating ischemic and bleeding events as "ischemic stroke equivalents" in order to compare a weighted benefit of 2 doses of dabigatran with each other, and with that of warfarin. RESULTS: Compared with warfarin, there was a significant decrease in ischemic stroke equivalents with both dabigatran doses: -0.92 per 100 patient years (95% confidence interval [CI]: -1.74 to -0.21, p = 0.02) with dabigatran 110 mg bid and -1.08 (95% CI: -1.86 to -0.34, p = 0.01) with dabigatran 150 mg bid. There was no significant difference in ischemic stroke equivalents between the 2 doses: -0.16 (95% CI: -0.80 to 0.43) comparing dabigatran 150 mg bid with 110 bid. When including death in the weighted benefit calculations, the results were similar. CONCLUSIONS: On a group level both doses of dabigatran as compared with warfarin have similar benefits when considering a weighted estimate including both efficacy and safety. The similar overall benefits of the 2 doses of dabigatran versus warfarin support individualizing the dose based on patient characteristics and physician and patient preferences. (Randomized Evaluation of Long Term Anticoagulant Therapy [RE-LY] With Dabigatran Etexilate; NCT00262600).
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Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Benzimidazóis/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Varfarina/administração & dosagem , beta-Alanina/análogos & derivados , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Dabigatrana , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Masculino , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento , Varfarina/efeitos adversos , Varfarina/uso terapêutico , beta-Alanina/administração & dosagem , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêuticoRESUMO
BACKGROUND & AIMS: Dabigatran is an oral and direct inhibitor of thrombin. In a study of patients with atrial fibrillation (the RE-LY trial), twice as many subjects given dabigatran reported dyspepsia-like symptoms compared with those given warfarin (controls). We analyzed data from this trial to quantify upper gastrointestinal nonbleeding adverse events (NB-UGI AEs). METHODS: We analyzed the AE database from the RE-LY trial (18,113 subjects) and assigned NB-UGI AEs to 4 groups: those associated with gastroesophageal reflux (GERD), upper abdominal pain and dyspepsia, dysmotility, or gastroduodenal injury. We analyzed frequency, timing, and severity, and clinical variables associated with NB-UGI AEs. RESULTS: NB-UGI AEs occurred in 16.9% of subjects given dabigatran and in 9.4% of controls (relative risk [RR], 1.81; 95% confidence interval [CI], 1.66%-1.97%; P < .001). Rates of AEs were not associated with the dose of dabigatran. Among subjects with any UGI symptom who were given dabigatran (n = 2045), symptoms were rated as mild in 46.3%, moderate in 44.8%, and severe in 8.9%; these values were similar to those of controls. GERD-associated NB-UGI AEs were most frequent among the 4 groups (compared with controls, RR, 3.71; 95% CI, 2.98%-4.62%; P < .001). Four percent of subjects stopped taking dabigatran because of NB-UGI AEs (most within 3 months of starting therapy), compared with 1.7% of controls (RR, 2.34; 95% CI, 1.90%-2.88%; P < .001). NB-UGI AEs slightly increased risk of major GI bleeding among subjects given dabigatran and controls (6.8% vs 2.3%, P < .001). CONCLUSIONS: Among patients given dabigatran for atrial fibrillation, NB-UGI AEs are generally mild or moderate; 4% stopped taking the drug over a median of 21.7 months. The greatest increase was in GERD-type NB-UGI AEs. These observations should guide management and prevention strategies.
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Antitrombinas/efeitos adversos , Antitrombinas/uso terapêutico , Benzimidazóis/efeitos adversos , Benzimidazóis/uso terapêutico , Dispepsia/induzido quimicamente , Dispepsia/epidemiologia , beta-Alanina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/tratamento farmacológico , Dabigatrana , Dispepsia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêuticoRESUMO
BACKGROUND: The Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial showed that dabigatran etexilate 150 mg BID was superior and dabigatran etexilate 110 mg BID was noninferior to warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation. In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and did not receive concomitant antiplatelets. METHODS AND RESULTS: All comparisons used a Cox proportional hazards model with adjustments made for risk factors for bleeding. A time-dependent analysis was performed when comparing patients with concomitant antiplatelets with those without. Of 18 113 patients, 6952 (38.4%) received concomitant aspirin or clopidogrel at some time during the study. Dabigatran etexilate 110 mg BID was noninferior to warfarin in reducing stroke and systemic embolism, whether patients received antiplatelets (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.70-1.25) or not (HR, 0.87; 95% CI, 0.66-1.15; interaction P=0.738). There were fewer major bleeds than warfarin in both subgroups (HR, 0.82; 95% CI, 0.67-1.00 for patients who used antiplatelets; HR, 0.79; 95% CI, 0.64-0.96 for patients who did not; interaction P=0.794). Dabigatran etexilate 150 mg BID reduced the primary outcome of stroke and systemic embolism in comparison with warfarin. This effect seemed attenuated among patients who used antiplatelets (HR, 0.80; 95% CI, 0.59-1.08) in comparison with those who did not (HR, 0.52; 95% CI, 0.38-0.72; P for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR, 0.93; 95% CI, 0.76-1.12 for patients who used antiplatelets; HR, 0.94; 95% CI, 0.78-1.15 for patients who did not; P for interaction=0.875). In the time-dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR, 1.60; 95% CI, 1.42-1.82). Dual antiplatelet seemed to increased this even more (HR, 2.31; 95% CI, 1.79-2.98). The absolute risks were lowest on dabigatran etexilate 110 mg BID in comparison with dabigatran etexilate 150 mg BID or warfarin. CONCLUSIONS: Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between dabigatran etexilate 110 mg BID and dabigatran etexilate 150 mg BID requires a careful assessment of characteristics that influence the balance between benefit and harm. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00262600.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Benzimidazóis/uso terapêutico , Embolia/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Dabigatrana , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Embolia/epidemiologia , Feminino , Hemorragia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin. METHODS AND RESULTS: RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (R(2)=0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65-6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85-1.00). CONCLUSIONS: Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
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Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Embolia/prevenção & controle , Internacionalidade , Acidente Vascular Cerebral/prevenção & controle , Varfarina/uso terapêutico , Idoso , Algoritmos , Fibrilação Atrial/complicações , Relação Dose-Resposta a Droga , Embolia/epidemiologia , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Modelos de Riscos Proporcionais , Análise de Regressão , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
BACKGROUND: Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required. METHODS AND RESULTS: The current analysis was undertaken to compare the periprocedural bleeding risk of patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial treated with dabigatran and warfarin. Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures, considering only the first procedure for each patient. A total of 4591 patients underwent at least 1 invasive procedure: 24.7% of patients received dabigatran 110 mg, 25.4% received dabigatran 150 mg, and 25.9% received warfarin, P=0.34. Procedures included: pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%), and joint replacement (6.2%). Among patients assigned to either dabigatran dose, the last dose of study drug was given 49 (35-85) hours before the procedure on comparison with 114 (87-144) hours in patients receiving warfarin, P<0.001. There was no significant difference in the rates of periprocedural major bleeding between patients receiving dabigatran 110 mg (3.8%) or dabigatran 150 mg (5.1%) or warfarin (4.6%); dabigatran 110 mg versus warfarin: relative risk, 0.83; 95% CI, 0.59 to 1.17; P=0.28; dabigatran 150 mg versus warfarin: relative risk, 1.09; 95% CI, 0.80 to 1.49; P=0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran 110 mg, 17.7% with dabigatran 150 mg, and 21.6% with warfarin: dabigatran 110 mg; relative risk, 0.82; 95% CI, 0.48 to 1.41; P=0.47; dabigatran 150 mg: relative risk, 0.82; 95% CI, 0.50 to 1.35; P=0.44. CONCLUSIONS: Dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patients having urgent surgery. Dabigatran facilitated a shorter interruption of oral anticoagulation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.