Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Improved risk stratification of patients with atrial fibrillation: an integrated GARFIELD-AF tool for the prediction of mortality, stroke and bleed in patients with and without anticoagulation.

OBJECTIVES: To provide an accurate, web-based tool for stratifying patients with atrial fibrillation to facilitate decisions on the potential benefits/risks of anticoagulation, based on mortality, stroke and bleeding risks. DESIGN: The new tool was developed, using stepwise regression, for all and then applied to lower risk patients. C-statistics were compared with CHA2DS2-VASc using 30-fold cross-validation to control for overfitting. External validation was undertaken in an independent dataset, Outcome Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). PARTICIPANTS: Data from 39 898 patients enrolled in the prospective GARFIELD-AF registry provided the basis for deriving and validating an integrated risk tool to predict stroke risk, mortality and bleeding risk. RESULTS: The discriminatory value of the GARFIELD-AF risk model was superior to CHA2DS2-VASc for patients with or without anticoagulation. C-statistics (95% CI) for all-cause mortality, ischaemic stroke/systemic embolism and haemorrhagic stroke/major bleeding (treated patients) were: 0.77 (0.76 to 0.78), 0.69 (0.67 to 0.71) and 0.66 (0.62 to 0.69), respectively, for the GARFIELD-AF risk models, and 0.66 (0.64-0.67), 0.64 (0.61-0.66) and 0.64 (0.61-0.68), respectively, for CHA2DS2-VASc (or HAS-BLED for bleeding). In very low to low risk patients (CHA2DS2-VASc 0 or 1 (men) and 1 or 2 (women)), the CHA2DS2-VASc and HAS-BLED (for bleeding) scores offered weak discriminatory value for mortality, stroke/systemic embolism and major bleeding. C-statistics for the GARFIELD-AF risk tool were 0.69 (0.64 to 0.75), 0.65 (0.56 to 0.73) and 0.60 (0.47 to 0.73) for each end point, respectively, versus 0.50 (0.45 to 0.55), 0.59 (0.50 to 0.67) and 0.55 (0.53 to 0.56) for CHA2DS2-VASc (or HAS-BLED for bleeding). Upon validation in the ORBIT-AF population, C-statistics showed that the GARFIELD-AF risk tool was effective for predicting 1-year all-cause mortality using the full and simplified model for all-cause mortality: C-statistics 0.75 (0.73 to 0.77) and 0.75 (0.73 to 0.77), respectively, and for predicting for any stroke or systemic embolism over 1 year, C-statistics 0.68 (0.62 to 0.74). CONCLUSIONS: Performance of the GARFIELD-AF risk tool was superior to CHA2DS2-VASc in predicting stroke and mortality and superior to HAS-BLED for bleeding, overall and in lower risk patients. The GARFIELD-AF tool has the potential for incorporation in routine electronic systems, and for the first time, permits simultaneous evaluation of ischaemic stroke, mortality and bleeding risks. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier for GARFIELD-AF (NCT01090362) and for ORBIT-AF (NCT01165710)

Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-AF.

AIMS: The relationship between outcomes and time after diagnosis for patients with non-valvular atrial fibrillation (NVAF) is poorly defined, especially beyond the first year. METHODS AND RESULTS: GARFIELD-AF is an ongoing, global observational study of adults with newly diagnosed NVAF. Two-year outcomes of 17 162 patients prospectively enrolled in GARFIELD-AF were analysed in light of baseline characteristics, risk profiles for stroke/systemic embolism (SE), and antithrombotic therapy. The mean (standard deviation) age was 69.8 (11.4) years, 43.8% were women, and the mean CHA2DS2-VASc score was 3.3 (1.6); 60.8% of patients were prescribed anticoagulant therapy with/without antiplatelet (AP) therapy, 27.4% AP monotherapy, and 11.8% no antithrombotic therapy. At 2-year follow-up, all-cause mortality, stroke/SE, and major bleeding had occurred at a rate (95% confidence interval) of 3.83 (3.62; 4.05), 1.25 (1.13; 1.38), and 0.70 (0.62; 0.81) per 100 person-years, respectively. Rates for all three major events were highest during the first 4 months. Congestive heart failure, acute coronary syndromes, sudden/unwitnessed death, malignancy, respiratory failure, and infection/sepsis accounted for 65% of all known causes of death and strokes for <10%. Anticoagulant treatment was associated with a 35% lower risk of death. CONCLUSION: The most frequent of the three major outcome measures was death, whose most common causes are not known to be significantly influenced by anticoagulation. This suggests that a more comprehensive approach to the management of NVAF may be needed to improve outcome. This could include, in addition to anticoagulation, interventions targeting modifiable, cause-specific risk factors for death. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Simplified state update calculation for fast and accurate digital emulation of CNN dynamics

Trabajo presentado al 12th CNNA celebrado en Berkeley (USA) del 3 al 5 de febrero de 2010.Compared to other one-step integration methods, the 4th-order Runge-Kutta is much more accurate while still consisting in a rather reduced algorithmic structure. However, in terms of the computing power, it is more expensive than others. While the Forward Euler's method updates the state variable with a single evaluation of the derivative, 4th-order Runge-Kutta's method requires four. This is the reason why, when simulation speed is a central matter, e. g. in the digital emulation of CNN dynamics, the speed-accuracy trade-off is resolved in favour of the simpler, though less accurate, methods. A workaround for the computationally intensive calculation of the state variable update can be found for certain CNN models. If a FSR CNN model is employed, where the state variable is not allowed to go beyond the limits of the linear region of the cell output characteristic, the output can be identified with the state. In these conditions, and having linear templates, the update of the state variable can be computed, for a 4th-order Runge-Kutta's method, with a single function evaluation. It means that a digital emulation of the CNN dynamics following this method is as light-weighted as a Forward Euler's integrator, but much more accurate.This work is partially funded by grant 2006-TIC-2352 (CICE/JA).Peer Reviewe

Design of a smart SiPM based on focal-plane processing elements for improved spatial resolution in PET

Comunicación presentada al "V Bioelectronics, Biomedical, and Bioinspired Systems V and Nanotechnology" celebrado en Praga (República Checa) del 18 al 20 de Abril del 2011.Single-photon avalanche diodes are compatible with standard CMOS. It means that photo-multipliers for scintillation detectors in nuclear medicine (i. e. PET, SPECT) can be built in inexpensive technologies. These silicon photo-multipliers consist in arrays of, usually passively-quenched, SPADs whose output current is sensed by some analog readout circuitry. In addition to the implementation of photosensors that are sensitive to singlephoton events, analog, digital and mixed-signal processing circuitry can be included in the same CMOS chip. For instance, the SPAD can be employed as an event detector, and with the help of some in-pixel circuitry, a digitized photo-multiplier can be built in which every single-photon detection event is summed up by a counter. Moreover, this concurrent processing circuitry can be employed to realize low level image processing tasks. They can be efficiently implemented by this architecture given their intrinsic parallelism. Our proposal is to operate onto the light-induced signal at the focal plane in order to obtain a more elaborated record of the detection. For instance, by providing some characterization of the light spot. Information about the depth-of-interaction, in scintillation detectors, can be derived from the position and shape of the scintillation light distribution. This will ultimately have an impact on the spatial resolution that can be achieved. We are presenting the design in CMOS of an array of detector cells. Each cell contains a SPAD, an MOS-based passive quenching circuit and drivers for the column and row detection lines.This work is partially funded by the Andalusian Regional Government through project 2006-TIC-2352, by the Spanish Ministry of Science and Innovation through project TEC 2009-11812, co-funded by the European Regional Development Fund, and also supported by the Office of Naval Research (USA), through grant N000141110312.Peer Reviewe

Multi-resolution low-power Gaussian filtering by reconfigurable focal-plane binning

Comunicación presentada al "V Bioelectronics, Biomedical, and Bioinspired Systems V and Nanotechnology" celebrado en Praga (República Checa) del 18 al 20 de Abril del 2011.Gaussian filtering is a basic tool for image processing. Noise reduction, scale-space generation or edge detection are examples of tasks where different Gaussian filters can be successfully utilized. However, their implementation in a conventional digital processor by applying a convolution kernel throughout the image is quite inefficient. Not only the value of every single pixel is taken into consideration sucessively, but also contributions from their neighbors need to be taken into account. Processing of the frame is serialized and memory access is intensive and recurrent. The result is a low operation speed or, alternatively, a high power consumption. This inefficiency is specially remarkable for filters with large variance, as the kernel size increases significantly. In this paper, a different approach to achieve Gaussian filtering is proposed. It is oriented to applications with very low power budgets. The key point is a reconfigurable focal-plane binning. Pixels are grouped according to the targeted resolution by means of a division grid. Then, two consecutive shifts of this grid in opposite directions carry out the spread of information to the neighborhood of each pixel in parallel. The outcome is equivalent to the application of a 3×3 binomial filter kernel, which in turns is a good approximation of a Gaussian filter, on the original image. The variance of the closest Gaussian filter is around 0.5. By repeating the operation, Gaussian filters with larger variances can be achieved. A rough estimation of the necessary energy for each repetition until reaching the desired filter is below 20nJ for a QCIF-size array. Finally, experimental results of a QCIF proofof- concept focal-plane array manufactured in 0.35μm CMOS technology are presented. A maximum RMSE of only 1.2% is obtained by the on-chip Gaussian filtering with respect to the corresponding equivalent ideal filter implemented off-chip.This work is partially funded by the Andalusian Regional Government through project 2006-TIC-2352, by the Spanish Ministry of Science and Innovation through project TEC 2009-11812, co-funded by the European Regional Development Fund, and also supported by the Office of Naval Research (USA), through grant N000141110312.Peer Reviewe

Switched-capacitor networks for scale-space generation

Trabajo presentado al 20th ECCTD celebrado en Linkoping (Suecia) del 29 al 31 de agosto de 2011.In scale-space filtering signals are represented at several scales, each conveying different details of the original signal. Every new scale is the result of a smoothing operator on a former scale. In image processing, scale-space filtering is widely used in feature extractors as the Scale-Invariant Feature Transform (SIFT) algorithm. RC networks are posed as valid scale-space generators in focal-plane processing. Switched-capacitor networks are another alternative, as different topologies and switching rate offer a great flexibility. This work examines the parallel and the bilinear implementations as two different switched-capacitor network topologies for scale-space filtering. The paper assesses the validity of both topologies as scale-space generators in focal-plane processing through object detection with the SIFT algorithm.This work was supported by Xunta de Galicia and MICINN (Spain) under the contracts 10PXI206037PR and TEC2009-12686. The work of F. Pozas, R. Carmona and A. Rodríguez-Vázquez is partially supported by ONR (USA) through grant N000141110312, and MICINN (Spain) through project TEC2009-11812, that is co-funded by the European Regional Development Fund.Peer Reviewe

Gender differences and management of stroke risk of nonvalvular atrial fibrillation in an upper middle-income country: Insights from the CARMEN-AF registry

Background: Atrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. Objective: To describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. Methods: A total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014–2017). They were categorized according to Gender. Results: Overall, 48.6% were women, mean age 70 ± 12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). Conclusions: CARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC. Keywords: Atrial fibrillation, Gender, Thromboembolic risk, Antithrombotic therapy, Stroke, Mexic

Predictors of NOAC versus VKA use for stroke prevention in patients with newly diagnosed atrial fibrillation: Results from GARFIELD-AF

Introduction: A principal aim of the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) was to document changes in treatment practice for patients with newly diagnosed atrial fibrillation during an era when non–vitamin K antagonist oral anticoagulants (NOACs) were becoming more widely adopted. In these analyses, the key factors which determined the choice between NOACs and vitamin K antagonists (VKAs) are explored. Methods: Logistic least absolute shrinkage and selection operator regression determined predictors of NOAC and VKA use. Data were collected from 24,137 patients who were initiated on AC ± antiplatelet (AP) therapy (NOAC [51.4%] or VKA [48.6%]) between April 2013 and August 2016. Results: The most significant predictors of AC therapy were country, enrolment year, care setting at diagnosis, AF type, concomitant AP, and kidney disease. Patients enrolled in emergency care or in the outpatient setting were more likely to receive a NOAC than those enrolled in hospital (OR 1.16 [95% CI: 1.04-1.30], OR: 1.15 [95% CI: 1.05-1.25], respectively). NOAC prescribing seemed to be favored in lower-risk groups, namely, patients with paroxysmal AF, normotensive patients, and those with moderate alcohol consumption, but also the elderly and patients with acute coronary syndrome. By contrast, VKAs were preferentially used in patients with permanent AF, moderate to severe kidney disease, heart failure, vascular disease, and diabetes and with concomitant AP. Conclusion: GARFIELD-AF data highlight marked heterogeneity in stroke prevention strategies globally. Physicians are adopting an individualized approach to stroke prevention where NOACs are favored in patients with a lower stroke risk but also in the elderly and patients with acute coronary syndrome