Multiple scores have been proposed to stratify bleeding risk, but their value to guide dual antiplatelet therapy duration has never been appraised. We compared the performance of the CRUSADE (Can ...Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) scores in 1946 patients recruited in the Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) and assessed hemorrhagic and ischemic events in the 24- and 6-month dual antiplatelet therapy groups.
Bleeding score performance was assessed with a Cox regression model and C statistics. Discriminative and reclassification power was assessed with net reclassification improvement and integrated discrimination improvement. The C statistic was similar between the CRUSADE score (area under the curve 0.71) and ACUITY (area under the curve 0.68), and higher than HAS-BLED (area under the curve 0.63). CRUSADE, but not ACUITY, improved reclassification (net reclassification index 0.39, P=0.005) and discrimination (integrated discrimination improvement index 0.0083, P=0.021) of major bleeding compared with HAS-BLED. Major bleeding and transfusions were higher in the 24- versus 6-month dual antiplatelet therapy groups in patients with a CRUSADE score >40 (hazard ratio for bleeding 2.69, P=0.035; hazard ratio for transfusions 4.65, P=0.009) but not in those with CRUSADE score ≤40 (hazard ratio for bleeding 1.50, P=0.25; hazard ratio for transfusions 1.37, P=0.44), with positive interaction (Pint=0.05 and Pint=0.01, respectively). The number of patients with high CRUSADE scores needed to treat for harm for major bleeding and transfusion were 17 and 15, respectively, with 24-month rather than 6-month dual antiplatelet therapy; corresponding figures in the overall population were 67 and 71, respectively.
Our analysis suggests that the CRUSADE score predicts major bleeding similarly to ACUITY and better than HAS BLED in an all-comer population with percutaneous coronary intervention and potentially identifies patients at higher risk of hemorrhagic complications when treated with a long-term dual antiplatelet therapy regimen.
URL: http://clinicaltrials.gov. Unique identifier: NCT00611286.
Thermal water discharge within the gravity-driven groundwater flow system in the Alps and other similar areas around the world may be hidden in Quaternary deposits which, in these regions, often ...cover the regional aquifer. When thermal water drains into Quaternary deposits, the mixing of the deep thermal component and the cold shallow groundwater forms a thermal plume that extends parallel to the main groundwater flow in shallow system. In the Bled case study in Slovenia, the thermal water discharges from carbonate rocks into Quaternary glaciofluvial sediments, and as the Toplice spring at a rate of 5 l/s at an average temperature of 21.5 °C. Knowing the spatial extent and intensity of thermal outflow is essential to decision making related to the development and protection of this renewable resource. By approximating the thermal water outflow from a discharge zone as a planar source, a planar advective heat transport model can be used to evaluate its geometry and quantify rates. An analytical procedure follows rough assumptions leading to conservative results. Moreover, a numerical model using the FEFLOW code was applied for comparison with the simulations of the analytical model. The heat transport model was based on measured hydraulic parameters (e.g. groundwater levels) and borehole temperatures as well as on-site and international literature (e.g. dispersivity, thermal conductivity). Nine scenarios were applied accounting for different dimensions of the heat source and compared to the results of numerical simulations. Each scenario was verified by calculating the relative error between the analytical models and the measured borehole temperatures. The results confirm that the main outflow of thermal water can be determined using planar geometry, and is 200–300 m wide. The height of the thermal outflow zone is approximately 25 m, corresponding to the expected thickness of the direct contact between the fractured dolomite and the shallower Quaternary aquifer. Using the proposed widths and depths, the hidden natural thermal outflow rates are estimated at 57–86 l/s.
•Analytical model accounting for the planar heat transport and numerical model were applied to evaluate the heat plume dimensions caused by thermal water.•Modelling results were compared with measured temperatures in boreholes.•The thermal water outflow is predominantly bound to a continuous surface, and secondary thermal outflows may occur in some cases.
There is uncertainty whether a focus on modifiable bleeding risk factors offers better prediction of major bleeding than other existing bleeding risk scores.
This study compared a score based on ...numbers of the modifiable bleeding risk factors recommended in the 2016 European guidelines (“European risk score”) versus other published bleeding risk scores that have been derived and validated in atrial fibrillation subjects (HEMORR2HAGES, HAS-BLED, ATRIA, and ORBIT) in a large hospital-based cohort of Chinese inpatients with atrial fibrillation.
The European score had modest predictive ability for major bleeding (c-index 0.63, 95% confidence interval 0.56-0.69) and intracranial hemorrhage (0.72, 0.65-0.79) but nonsignificantly (and poorly) predicted extracranial bleeding (0.55, 0.54-0.56; P = .361). The HAS-BLED score was superior to predict bleeding events compared with the European score, with the differences between c-indexes of 0.10-0.12 (Delong test, all P < .05), net reclassification improvement values of 13.0%-34.5% (all P < .05), and integrated discrimination improvement values of 0.7%-1.4% (all P < .05). The European score had similar predictive value to other bleeding risk schemes (HEMORR2HAGES, ATRIA, and ORBIT) for major bleeding and intracranial hemorrhage (all P > .05). Decision curve analysis clearly shows that HAS-BLED had better net benefit of predicting major bleeding compared with the European score.
Relying on bleeding risk assessment using modifiable bleeding risk factors alone is an inferior strategy for predicting atrial fibrillation patients for major bleeding. Our observations reaffirm the Asian guideline recommendations with HAS-BLED for bleeding risk assessment in patients with atrial fibrillation.
A menudo la evaluación de los riesgos de ictus y hemorragia en la fibrilación auricular (FA) es basal para predecir los resultados años después. Sin embargo, estos riesgos no son estáticos. Se ...investiga si los cambios dinámicos en CHA2DS2-VASc y HAS-BLED a lo largo del tiempo modifican la predicción del riesgo.
Se incluyó a pacientes con FA estables en tratamiento con antagonistas de la vitamina K. Durante 6 años de seguimiento, se registraron todos los ictus isquémicos/accidentes isquémicos transitorios (AIT) y hemorragias mayores. El CHA2DS2-VASc y HAS-BLED se revaluaron cada 2 años y se investigaron los resultados clínicos en periodos de 2 años.
Se incluyó a 1.361 pacientes (medias de CHA2DS2-VASc y HAS-BLED, 4,0±1,7 y 2,9±1,2). Durante el seguimiento, 156 pacientes (11,5%) sufrieron un ictus isquémico/AIT y 269 (19,8%), una hemorragia mayor. En comparación con el valor basal, el CHA2DS2-VASc recalculado a los 2 años presentó mayor capacidad predictiva de ictus isquémico/AIT durante el periodo de 2-4 años. El índice de mejoría de la discriminación (IDI) y el índice de reclasificación neta (NRI) mostraron mejoras en la sensibilidad y mejor reclasificación. El CHA2DS2-VASc recalculado a los 4 años arrojó un mejor rendimiento predictivo que el basal durante el periodo de 4-6 años, con una mejora en el IDI y una mejora de la reclasificación. El HAS-BLED recalculado a los 2 años presentó mayor capacidad predictiva de hemorragia mayor que el basal durante el período de 2-4 años, con mejoras significativas en la sensibilidad y la reclasificación. Se observó un ligero aumento en la sensibilidad del HAS-BLED recalculado a los 4 años respecto al basal.
En pacientes con FA, los riesgos de ictus y hemorragia son dinámicos y cambian con el tiempo. Las escalas CHA2DS2-VASc y HAS-BLED deben revaluarse con regularidad, especialmente para una precisa predicción del riesgo de ictus.
Stroke and bleeding risks in atrial fibrillation (AF) are often assessed at baseline to predict outcomes years later. We investigated whether dynamic changes in CHA2DS2-VASc and HAS-BLED scores over time modify risk prediction.
We included patients with AF who were stable while taking vitamin K antagonists. During a 6-year follow-up, all ischemic strokes/transient ischemic attacks (TIAs) and major bleeding events were recorded. CHA2DS2-VASc and HAS-BLED were recalculated every 2-years and tested for clinical outcomes at 2-year periods.
We included 1361 patients (mean CHA2DS2-VASc and HAS-BLED 4.0±1.7 and 2.9±1.2). During the follow-up, 156 (11.5%) patients had an ischemic stroke/TIA and 269 (19.8%) had a major bleeding event. Compared with the baseline CHA2DS2-VASc, the CHA2DS2-VASc recalculated at 2 years had higher predictive ability for ischemic stroke/TIA during the period from 2 to 4 years. Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) showed improvements in sensitivity and better reclassification. The CHA2DS2-VASc recalculated at 4 years had better predictive performance than the baseline CHA2DS2-VASc during the period from 4 to 6 years, with an improvement in IDI and an enhancement of the reclassification. The recalculated HAS-BLED at 2-years had higher predictive ability than the baseline score for major bleeding during the period from 2 to 4 years, with significant improvements in sensitivity and reclassification. A slight enhancement in sensitivity was observed with the HAS-BLED score recalculated at 4 years compared with the baseline score.
In AF patients, stroke and bleeding risks are dynamic and change over time. The CHA2DS2-VASc and HAS-BLED scores should be regularly reassessed, particularly for accurate stroke risk prediction.
Various bleeding risk prediction schemes, such as the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized Ratio, Elderly, ...Drugs/alcohol (HAS-BLED), Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA), and Outcomes Registry for Better Informed Treatment (ORBIT) scores, have been proposed in patients with atrial fibrillation. We compared the relative predictive values of these bleeding risk scores for clinically relevant bleeding and the relationship of ATRIA and ORBIT scores to the quality of anticoagulation control on warfarin, as reflected by time in therapeutic range.
We conducted a post hoc ancillary analysis of clinically relevant bleeding and major bleeding events among 2293 patients receiving warfarin therapy in the AMADEUS trial.
Only HAS-BLED was significantly predictive for clinically relevant bleeding, and all 3 risk scores were predictive for major bleeding. The predictive performance of HAS-BLED was modest, as reflected by c-indexes of 0.59 (P < .001) and 0.65 (P < .002) for clinically relevant bleeding and major bleeding, respectively. The HAS-BLED score performed better than the ATRIA (P = .002) or ORBIT (P = .001) score in predicting any clinically relevant bleeding. Only the HAS-BLED score was significantly associated with the risk for both bleeding outcomes on Cox regression analysis (any clinically relevant bleeding: hazard ratio, 1.85; 95% confidence interval, 1.43-2.40, P < .001; major bleeding: hazard ratio, 2.40; 95% confidence interval, 1.28-4.52; P = .007). There were strong inverse correlations of ATRIA and ORBIT scores to time in therapeutic range as a continuous variable (low risk ATRIA, r = −0.96; P = .003; ORBIT, r = −0.96; P = .003). Improvement in the predictive performance for both ATRIA and ORBIT scores for any clinically relevant bleeding was achieved by adding time in therapeutic range to both scores, with significant differences in c-indexes (P = .001 and P = .002, respectively), net reclassification improvement, and integrated discriminant improvement (both P < .001).
All 3 bleeding risk prediction scores demonstrated modest predictive ability for bleeding outcomes, although the HAS-BLED score performed better than the ATRIA or ORBIT score. Significant improvements in both ATRIA and ORBIT score prediction performances were achieved by adding time in therapeutic range to both scores.
Lower Cretaceous syn-orogenic sediments derived from the obducted ophiolites of the Meliata–Maliac–Vardar (Neotethys) Ocean are typically found in the Dinarides and the Austroalpine units. ...Correlative flysch-type deposits linking both regions through the Southern Alps had been reported from the Bohinj area (NW Slovenia), but their stratigraphic and structural framework remained poorly known. Our research focused on stratigraphic and structural field studies in a 50 km
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area between Lake Bled and Lake Bohinj in the Julian Alps. The mixed carbonate–siliciclastic sediments, informally named the Studor formation, range in age from the Valanginian (possibly late Berriasian) to the Aptian. They occur on top of two different stratigraphic successions, which we assign to two separate nappes. The first succession consists of deep-water Middle Triassic to Lower Cretaceous deposits of the Bled Basin and belongs to the Pokljuka Nappe, which is the uppermost nappe of the Julian nappe stack. The second succession consists of Upper Triassic to Lower Jurassic platform carbonates and a thin Jurassic–Cretaceous deep-water sequence. This succession was deposited in the marginal area of the Julian Carbonate Platform/Julian High and now belongs to the underlying Krn Nappe. The original (Dinaric) thrust contacts between the Pokljuka and Krn nappes are obliterated by younger deformations. The present-day boundaries between these two nappes are steep NE–SW and younger NW–SE trending faults. The post-nappe deformation sequence characterizing the Alps–Dinarides transition zone has been recognized: (1) Oligocene–Early Miocene NW–SE contraction; (2) Early–Middle Miocene extension; and (3) Late Miocene to recent inversion and transpression.
Background and Aim: The increasing prevalence and high hospitalization rates make atrial fibrillation (AF) a significant healthcare strain. However, there are limited data regarding the length of ...hospital stay (LOS) of AF patients. Our purpose was to determine the main drivers of extended LOS of AF patients. Methods: All AF patients, hospitalized consecutively in a tertiary cardiology center, from January 2018 to February 2020 were included in this retrospective cohort study. Readmissions were excluded. Prolonged LOS was defined as more than seven days (the upper limit of the third quartile). Results: Our study included 949 AF patients, 52.9% females. The mean age was 72.5 ± 10.3 years. The median LOS was 4 days. A total of 28.7% had an extended LOS. Further, 82.9% patients had heart failure (HF). In multivariable analysis, the independent predictors of extended LOS were: acute coronary syndromes (ACS) (HR 4.60, 95% CI 1.66–12.69), infections (HR 2.61, 95% CI 1.44–3.23), NT-proBNP > 1986 ng/mL (HR 1.96, 95% CI 1.37–2.82), acute decompensated HF (ADHF) (HR 1.76, 95% CI 1.23–2.51), HF with reduced ejection fraction (HFrEF) (HR 1.69, 95% CI 1.15–2.47) and the HAS-BLED score (HR 1.42, 95% CI 1.14–1.78). Conclusion: ACS, ADHF, HFrEF, increased NT-proBNP levels, infections and elevated HAS-BLED were independent predictors of extended LOS, while specific clinical or therapeutical AF characteristics were not.
The HAS-BLED and ORBIT scores have been proposed to assess bleeding risk in anticoagulated atrial fibrillation patients. We performed a systematic review and meta-analysis to compare the predictive ...ability by using these two scores.
We searched the Cochrane Library, Elsevier and PubMed databases for related studies. Statistical analysis was performed with Revman 5.3 Manager software. We chose the C-statistic to reflect the diagnostic value.
In our seven selected studies, the pooled C- statistic of continuous variables for major bleeding was 0.65 (0.60,0.69) for ORBIT and 0.63 (0.60,0.66) for HAS-BLED. Compared with HAS-BLED, more anticoagulated AF patients (88.45% versus 32.59%) and major bleeding events (75.57% versus 25.57%) were categorized as low risk. The ORBIT score had a 1.21, 1.73 and 1.44-fold elevated risk of major bleeding in the low, intermediate and high risk strata respectively. Calibration analysis demonstrated that the ORBIT score under-predicted major bleeding in the low, intermediate, and high risk stratifications, where a odds ratio of 0.64 (0.37-1.10), 0.63 (0.38-1.05) and 0.64 (0.38-1.06), respectively.
Compared with HAS-BLED , the ORBIT score does not perform better in predicting major bleeding events in anticoagulated atrial fibrillation patients. More anticoagulated AF patients and major bleeding events were categorized as low risk when using ORBIT.
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