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

High Temperature Mechanical Properties of AZ91 Magnesium Alloy Weld Joint

Magnesium alloys are widely applied in aircraft and automotive industry, due to their low density and high specific strength. Welding methods can be used to join Mg alloy elements and to repair or regenerate defective or worn-out castings. Therefore the influence of weld joint’s microstructure on mechanical properties needs to be studied. In present paper high temperature mechanical properties of AZ91 Mg alloy weld joint was investigated. Tensile tests were conducted in temperature range between 20 and 200°C. Ultimate tensile strength decreased as the temperature increased from 50°C. At temperature up to 150°C rapture occurred in the base metal, at 200°C rupture location switched to the weld fusion zone. Based on metallographic and fractographic observation, the fracture mechanism was described. Macro crack formed from the merger of micro cracks occurring at massive β phase precipitates

Synthesis and Thermal Properties of Cerium-Dysprosium Oxide

The paper presents results of investigation on synthesis and characterization of cerium-dysprosium oxide. The input powders - dysprosium oxide Dy,sub>2O3 and cerium oxide CeO2 - were mixed so as to obtain equimolar ratio of cations, milled in alcohol and synthesized via solid state reaction process at 1350°C under 15MPa in vacuum for 2h. The microstructure, phase composition and thermal properties were analyzed. The obtained material was multiphase. Non-stoichiometric compounds were identified. Thermal diffusivity of investigated material decreased in the temperature range of 25-1000°C from 0,71 to 0,45 mm2/s

Synthesis and Thermal Properties of Europium-Cerium Oxide as a New Fluorite-Type Ceramic Material for Thermal Barrier Coatings Applications

In the present paper the structure and thermal properties of europium cerium oxides were investigated. The material for the research was obtained via solid state synthesis. The initial powders: ceria CeO2 and europia Eu2O3 were mixed in 1:1 mass ratio (non-stoichiometric proportion with the excess of CeO2) and milled. The sintering process was performed using high temperature vacuum press at 1350°C. Calorimetric analysis was conducted both for initial powders and milled mixture. The structure, phase composition and thermal diffusivity of obtained material were investigated in as-sintered condition. It was revealed that the obtained material was multi-phase. Non-stoichiometric phases including Ce0.5Eu0.5O1.75 with fluorite type structure and different lattice parameters were present. Thermal diffusivity decreased in the range from 25 to 900°C from 1.49 to 0.57 mm2 /s and then increased to 0.70 mm2 /s at 1400°C

Wpływ parametrów odlewania grawitacyjnego na mikrostrukturę i właściwości stopów magnezu

The paper present the influence of modifying process on chemical composition, microstructure, and selected properties of Mg alloys. Two sand-casting creep-resistant alloys, Elektron 21 and WE43, were analyzed in various forms: without modifiers, with the amount of modifier suggested by the producer, and with this amount increased by 50% and 100%. The volume fraction of eutectic areas, tensile strength, and yield strength were measured and the fluidity and linear contraction were analyzed. The research shows that, in contrast to what is widely assumed to be a positive influence of rare-earth elements on Mg alloys properties, a large increase in the amount of modifiers does not always lead to an improvement in the alloy properties. However, the results are tentative because they may have been influenced by the melting technology used, which can be improved. Rare-earth elements tend to react with fluxes, which could lead to a decrease in mechanical properties and fluidity. More research is planned wherein the alloys are melted under a protective atmosphere.W artykule zaprezentowano wpływ modyfikacji odlewniczych stopów magnezu na skład chemiczny, mikrostrukturę i wybrane właściwości. Badano 2 stopy odlewane do form piaskowych, przeznaczone do pracy w podwyższonej temperaturze: Elektron 21 i WE43 w czterech wariantach: bez modyfikacji, z ilością modyfikatorów dodaną zgodnie z procedura zalecana przez producenta, powiększona o 50 i 100%. Wykonano ilościową analizę udziału objętościowego eutektyk, zmierzono wytrzymałość na rozciąganie, granice plastyczności, wykonano próbę lejności oraz skurczu liniowego. Wykazano, że mimo powszechnie uznanego za pozytywny wpływu metali ziem rzadkich na właściwosci stopów Mg dodawanie zwiększonych ilości modyfikatorów w stosunku do zaleceń producentów nie zawsze ma dobry wpływ na wyniki. Prawdopodobnie duży wpływ na wyniki badań miała technologia odlewania, wymagająca poprawy - zastosowane topniki mogą reagowac z pierwiastkami stopowymi i powodować obniżenie właściwości mechanicznych i lejności. W przyszłości planowane są podobne badania dla stopów topionych w atmosferze gazowej

Synthesis, Characterization and Thermal Diffusivity of Holmium and Praseodymium Zirconates

A2B2O7 oxides with pyrochlore or defected fluorite structure are among the most promising candidates for insulation layer material in thermal barrier coatings. The present paper presents the procedure of synthesis of holmium zirconate Ho2Zr2O7 and praseodymium zirconate Pr2Zr2O7 via Polymerized-Complex Method (PCM). Thermal analysis of precursor revealed that after calcination at relatively low temperature (700°C) fine-crystalline, single-phase material is obtained. Thermal diffusivity was measured in temperature range 25-200°C, Ho2Zr2O7 exhibits lower thermal diffusivity than Pr2Zr2O7. Additionally, PrHoZr2O7 was synthesized. The powder in as-calcined condition is single-phase, but during the sintering decomposition of solid solution took place and Ho-rich phase precipitated. This material exhibited the best insulating properties among the tested ones

Synthesis, Characterization and Thermal Diffusivity of Holmium and Praseodymium Zirconates

A2B2O7 oxides with pyrochlore or defected fluorite structure are among the most promising candidates for insulation layer material in thermal barrier coatings. The present paper presents the procedure of synthesis of holmium zirconate Ho2Zr2O7 and praseodymium zirconate Pr2Zr2O7 via Polymerized-Complex Method (PCM). Thermal analysis of precursor revealed that after calcination at relatively low temperature (700°C) fine-crystalline, single-phase material is obtained. Thermal diffusivity was measured in temperature range 25-200°C, Ho2Zr2O7 exhibits lower thermal diffusivity than Pr2Zr2O7. Additionally, PrHoZr2O7 was synthesized. The powder in as-calcined condition is single-phase, but during the sintering decomposition of solid solution took place and Ho-rich phase precipitated. This material exhibited the best insulating properties among the tested ones