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 Flux Growth as a Tool for the Preparation of Mixed-Framework Metal-Y Silicates: A Systematic Evaluation of the Influence of Experimental Parameters

We report new aspects of the application of the flux-growth method for the preparation of single crystals of silicates, in particular, mixed-framework (octahedral–tetrahedral) metal-Y silicates, in air. The detailed investigations involve flux-growth syntheses in the system BaO–K₂O–Y₂O₃–SiO₂–MoO₃, in which various important run parameters have been varied in a systematic way (heating and cooling rates, <i>T</i>_max and duration of holding step, continuous or stepwise cooling, total duration of run, amount of MoO₃ solvent, Y₂O₃/SiO₂ molar ratio, size and filling volume of platinum crucible). The results demonstrate that the crystallization of various silicate structure types are strongly controlled by the Y₂O₃/SiO₂ molar ratios and the amount of MoO₃ solvent in the precursor mixtures. A decrease of the Y₂O₃/SiO₂ ratio, i.e., an increasing amount of SiO₂, promotes an increasing structural complexity of the silicates; nesosilicates crystallize at comparatively low SiO₂ concentrations, sorosilicates at intermediate ones, and framework silicates finally form only at high SiO₂ concentrations. An increasing MoO₃ concentration in the flux mixture also causes the growth of silicates with increasing SiO₄ connectivity. A range of minimum and maximum MoO₃ concentrations exist in which crystals of these framework silicates can be synthesized. Too high concentrations of Mo⁶⁺ cations in the melt handicap the crystal growth of Ba/K–Y-silicates. As expected, lower cooling rates lead to better-developed crystals and a higher crystal yield. Unexpectedly, both the total mass loss by evaporation and the crucible size have no influence on the crystal growth of the silicates. Also, a holding step at <i>T</i>_max is not necessary for the crystallization of the silicates. The crystals obtained were characterized by scanning electron microscopy, chemical analyses, and single-crystal and powder X-ray diffraction (including Rietveld refinement)

Paratooite-(La), a new lanthanum-dominant rare-earth copper carbonate from Paratoo, South Australia

Copyright © 2006 The Mineralogical SocietyParatooite-(La) is a new lanthanum-dominant rare-earth copper carbonate from the Paratoo copper mine, near Yunta, Olary district, South Australia. Paratooite-(La) occurs as sheaves and radiating sprays of blade-like to tabular pale blue crystals in thin fissures in a slaty country rock. Individual crystals are typically 50–200 μm in maximum dimension but <5 μm thick. Associated minerals include donnayite-(Y), kamphaugite-(Y), and bastnäsite-(La). Electron microprobe and CHN analyses gave: La2O3 26.47; Pr2O3 7.74; Nd2O3 8.15; Sm2O3 0.66; Gd2O3 0.85; Y2O3 0.72; CaO 7.57; SrO 3.15; Na2O 3.3; CuO 5.77; F 0.24; CO2 32.05; NO2 1.12; −O=F −0.10; sum 100.03, yielding an empirical formula of (La3.54Ca2.94Na2.32Nd1.05Pr1.03Sr0.66Y0.14Gd0.10Sm0.0.8)Σ11.86Cu1.58(C15.84N0.53)O47.76F0.24. The simplified formula is (REE,Ca,Na,Sr)6Cu(CO3)8 or possibly REE3(Ca,Sr)2NaCu(CO3)8. The mineral is pale turquoise-blue to pale blue in colour, transparent, with a pearly to vitreous lustre and a pale blue streak. No cleavage was observed but the morphology and TEM studies indicate a cleavage parallel to {100}. The Mohs hardness is estimated to be 4. The strongest lines in the X-ray powder pattern are [dobs (Iobs) (hkl)]: 5.047 (53) (200); 4.786 (49) (021); 3.957 (43) (220); 3.468 (43) (012, 221); 2.927 (100) (202); 2.530 (52) (241); 2.344 (22) (420,103); 2.232 (20) (421). A synchrotron powder diffraction pattern was indexed on a primitive orthorhombic cell with a = 10.0862(5), b = 12.8088(6), c = 7.2360(4) Å, V = 934.8(1) Å3 and Z = 2. The crystal structure of the new mineral could not be determined but powder diffraction data indicate the space group is probably P222, Pmmm, P2221 or Pmm2. The measured density is 3.68(3) g/cm3 and the calculated density is 3.78 g/cm3. Paratooite-(La) is biaxial negative with α = 1.605(3), β = 1.696(3) and γ = 1.752(2); pleochroism is medium strong; X very pale bluish, Y and Z bluish (with greenish tint) with absorption Z ≈ Y ≫ X. Paratooite-(La) is a supergene mineral which precipitated from mildly basic carbonated groundwaters. The mineral is named for the type locality.A. Pring, K. Wallwork, J. Brugger and U. Kolitsc

Decrespignyite-(Y), a new copper yttrium rare earth carbonate chloride hydrate from Paratoo, South Australia

AbstractDecrespignyite-(Y) is a new copper yttrium rare earth carbonate chloride hydrate from the Paratoo copper mine, near Yunta, Olary district, South Australia. Decrespignyite-(Y) occurs as blue crusts, coatings and fillings in thin fissures on the slatey country rock. Individual pseudohexagonal platelets are typically 10–50 µm in maximum dimension and are often curved. Associated minerals include caysichite-(Y), donnayite-(Y), malachite and kamphaugite-(Y). Electron microprobe and CHN analyses gave: Y2O3 42.2; La2O3 0.1; Pr2O3 0.1; Nd2O3 1.3; Sm2O3 1.0; Gd2O3 4; Tb2O3 0.4; Dy2O3 3.7; Ho2O3 2.6; Er2O3 2.5; CaO 0.5; CuO 10.9; Cl 3.0; CO2 19.8; H2O 10.8, yielding an empirical formula of (Y3.08Gd0.22Dy0.16Ho0.11Er0.10Nd0.06Sm0.05Tb0.02La0.02Pr0.01Ca0.08)∑3.91Cu1.12(CO3)3.70-Cl0.7(OH)5.79·2.4H2O. The simplified formula is (Y,REE)4Cu(CO3)4Cl(OH)5·2H2O. The mineral is royal blue to turquoise-blue in colour, transparent, with a pearly to vitreous lustre and a pale blue streak. No cleavage was observed but the morphology suggests that cleavage would be on [010]. The Mohs' hardness is estimated to be 4. The strongest lines in the X-ray powder pattern are {dobs (Iobs) (hkl)} 22.79 (30) (010); 7.463 (30) (001); 7.086 (50) (011); 6.241 (100) (021); 4.216 (30) (12); 3.530 (40) (022); 3.336 (30) (032); 2.143 (30) (222, 01). The powder diffraction pattern was indexed on a monoclinic cell with a = 8.899(6), b = 22.77(2), c = 8.589(6)Å, β = 120.06(5)°, V = 1506.3(7) Å3 and Z = 4. The structure of the new mineral could not be determined but powder diffraction data indicate the space group is P2, Pm or P2/m. The measured density is 3.64(2) g/cm3 and the calculated density is 3.645 g/cm3. Decrespignyite-(Y) is biaxial negative with α = 1.604(4) and γ = 1.638(3) with β very close to γ pleochroism is medium strong; X very pale bluish, Y and Z bluish (with greenish tint). Decrespignyite-(Y) is a supergene mineral which precipitated from mildly basic carbonated ground waters. The mineral is named after Robert Champion de Crespigny, a prominent figure in the Australian mining industry and chancellor of the University of Adelaide.</jats:p