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

Temporal prediction of shallow landslides exploiting soil saturation degree derived by ERA5-Land products

ERA5-Land service has been released recently as an integral and operational component of Copernicus Climate Change Service. Within its set of climatological and atmospheric parameters, it provides soil moisture estimates at different soil depths, represeting an important tool for retrieving saturation degree for predicting natural hazards as shallow landslides. This paper represents an innovative attempt aiming to exploit the use of saturation degree derived from ERA5-Land soil moisture products in a data-driven model to predict the daily probability of occurence of shallow landslides. The study was carried out by investigating a multi-temporal inventory of shallow landslides occurred in Oltrepo Pavese (northern Italy). The achieved results follow: (i) ERA5-Land-derived saturation degree reconstructs well field trends measured in the study area until 1 m from ground; (ii) in agreement with the typical sliding surfaces depth, saturation degree values obtained since ERA5-Land 28-100 cm layer represent a significant predictor for the estimation of temporal probability of occurrence of shallow landslides, able especially to reduce overestimation of triggering events; (iii) saturation degree estimated by ERA5-Land 28-100 cm layer allows to detect soil hydrological conditions leading to triggering in the study area, represented by saturation degree in this layer close to complete saturation. Even if other works of research are required in different geological and geomorphological settings, this study demonstrates that ERA5-Land-derived saturation degree could be implemented to identify triggering conditions and to develop prediction methods of shallow landslides, thanks also to its free availability and constantly updating with a delay of 5 days

SM2RAIN-CCI: a new global long-term rainfall data set derived from ESA CCI soil moisture

Accurate and long-term rainfall estimates are the main inputs for several applications, from crop modeling to climate analysis. In this study, we present a new rainfall data set (SM2RAIN-CCI) obtained from the inversion of the satellite soil moisture (SM) observations derived from the ESA Climate Change Initiative (CCI) via SM2RAIN (Brocca et al., 2014). Daily rainfall estimates are generated for an 18-year long period (1998–2015), with a spatial sampling of 0.25° on a global scale, and are based on the integration of the ACTIVE and the PASSIVE ESA CCI SM data sets.The quality of the SM2RAIN-CCI rainfall data set is evaluated by comparing it with two state-of-the-art rainfall satellite products, i.e. the Tropical Measurement Mission Multi-satellite Precipitation Analysis 3B42 real-time product (TMPA 3B42RT) and the Climate Prediction Center Morphing Technique (CMORPH), and one modeled data set (ERA-Interim). A quality check is carried out on a global scale at 1° of spatial sampling and 5 days of temporal sampling by comparing these products with the gauge-based Global Precipitation Climatology Centre Full Data Daily (GPCC-FDD) product. SM2RAIN-CCI shows relatively good results in terms of correlation coefficient (median value  &gt;  0.56), root mean square difference (RMSD, median value  &lt;  10.34 mm over 5 days) and bias (median value  &lt;  −14.44 %) during the evaluation period. The validation has been carried out at original resolution (0.25°) over Europe, Australia and five other areas worldwide to test the capabilities of the data set to correctly identify rainfall events under different climate and precipitation regimes.The SM2RAIN-CCI rainfall data set is freely available at https://doi.org/10.5281/zenodo.846259

Semioccluded Vocal Tract Exercises Improve Self-Perceived Voice Quality in Healthy Actors

Summary: Purpose.Semi-occluded vocal tract exercises (SOVTE) have shown to lead to more effective andefficient vocal production for individuals with voice disorders and for singers. The aim of the present study is toinvestigate the effects of a 10-minute SOVTE warm-up protocol on the actors\u2019voice.Methods.Twenty-seven professional theater actors (16 females) without voice complaints were audio-recordedwhile reading aloud, with their acting voice, a short dramatic passage at four time points. Recordings were made:the day before the show, just before and soon after the warm-up protocol which was performed prior to the showand soon after the show. The voice quality was acoustically and auditory-perceptually evaluated and quantifiedat each time point by blinded raters. Self-assessment parameters anonymously collected pre and post exercisingwere also analyzed.Results.No statistically significant differences on perceptual ratings and acoustic parameters were foundbetween pre/post exercise sessions and males/females. A statistically significant improvement was detected in theself-assessment parameters concerning comfort of production, sonorousness, vocal clarity and power.Conclusions.Vocal warm-up with the described SOVTE protocol was effective in determining a self-perceivedimprovement in comfort of production, voice quality and power, although objective evidence was missing. Thisstraightforward protocol could thus be beneficial if routinely utilized by professional actors to facilitate the voiceperformance

Development of a data-driven model for spatial and temporal shallow landslide probability of occurrence at catchment scale

A combined method was developed to forecast the spatial and the temporal probability of occurrence of rainfall-induced shallow landslides over large areas. The method also allowed to estimate the dynamic change of this probability during a rainfall event. The model, developed through a data-driven approach basing on Multivariate Adaptive Regression Splines technique, was based on a joint probability between the spatial probability of occurrence (susceptibility) and the temporal one. The former was estimated on the basis of geological, geomorphological, and hydrological predictors. The latter was assessed considering short-term cumulative rainfall, antecedent rainfall, soil hydrological conditions, expressed as soil saturation degree, and bedrock geology. The predictive capability of the methodology was tested for past triggering events of shallow landslides occurred in representative catchments of Oltrepò Pavese, in northern Italian Apennines. The method provided excellently to outstanding performance for both the really unstable hillslopes (area under ROC curve until 0.92, true positives until 98.8%, true negatives higher than 80%) and the identification of the triggering time (area under ROC curve of 0.98, true positives of 96.2%, true negatives of 94.6%). The developed methodology allowed us to obtain feasible results using satellite-based rainfall products and data acquired by field rain gauges. Advantages and weak points of the method, in comparison also with traditional approaches for the forecast of shallow landslides, were also provided

Exploiting a constellation of satellite soil moisture sensors for accurate rainfall estimation

A merging procedure is applied to five daily rainfall estimates achieved via SM2RAIN applied to the soil moisture products obtained by the Advanced SCATterometer, the Advanced Microwave Scanning Radiometer 2, the Soil Moisture Active and Passive mission, the Soil Moisture and Ocean Salinity mission and backscattering observations of RapidScat. The precipitation estimates are evaluated against dense ground networks in the period ranging from April to December, 2015, in India and in Italy, at 0.25°/daily spatial/temporal resolution. The merged product derived by combining the different SM2RAIN rainfall products shows better results in term of statistical and categorical metrics with respect to the use of the single products. A good agreement with reference to ground observations is obtained, with median correlations equal to 0.65 and 0.77 in India and in Italy, respectively. The merged dataset is found to slightly outperform those of the IMERG product of the Global Precipitation Measurement mission underlying the large potential of the proposed approach