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)

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

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

Wpływ temperatury na zawartość cukrów rozpuszczalnych i jakość fizjologiczną nasion łubinu żółtego

Rośliny uprawiano w fitotronie w temperaturach 15°C, 20°C i 28°C przy 12 godzinnej długości dnia. W pełnej dojrzałości fizjologicznej nasiona były zebrane i określono w nich zawartość oligosacharydów rodziny rafinozy, galaktozylocyklitoli i cyklitoli. Stachioza była cukrem dominującym bez względu na temperaturę dojrzewania. Nasiona dojrzewające temp. 15°C miały większą masę, niż nasiona uprawiane w temp. 28°C. Temperatura modyfikowała gromadzenie oligosacharydów rodziny rafinozy. Nasiona uprawiane w temp. 28°C gromadziły znaczące ilości galaktozylocyklitoli serii D-pinitolu. Nasiona dojrzewające w temp. 28°C charakteryzowały się wzmożoną syntezą wyższych galaktozylooligomerów, tj. ciceritolu, digalacto-myo-inositolu.The plants were cultivated in phytotrone at 15°C, 20°C and 28°C with 12 hour illumination. Seeds being in full physiological maturity were collected and the levels of oligosaccharides of raffinose family, galactosyl cyclitols and cyclitols were estimated. Stachyose was a dominant oligosaccharide regardless the ripening temperature of the seeds. The seeds ripening at 15°C had a much bigger mass of the seed than the plants grown at 28°C. The temperature also modified the accumulation of raffinose family oligosaccharides. The seeds grown at 28°C accumulated significant amounts of galactosyl cyclitols of D-pinitol series. Seeds maturation at 28°C also favored accumulation of higher galactosyl oligomers ; (ciceritol, digalacto-myo-inositol)

Composition of seed soluble carbohydrates and ultrastructural diversity of testa in lupins from the Mediterranean Region

This article present a comparison of soluble sugar levels in seeds of Lupinus atlanticus, Lupinus cosentinii, Lupinus palaestinus and Lupinus pilosus, Lupinus hispanicus subsp. hispanicus and Lupinus luteus of Juno variety. Considering that sugars are accumulated in embryos, only the embryonic tissues were used for biochemical analyses. Additionally, the share of testa and embryo in seed tissues was evaluated. The seed-coat thickness was measured using scanning electron microscopy. The seed coat had the largest share in seeds of Lupinus pilosus and Lupinus palaestinus, and the least share in seeds of Lupinus hispanicus subsp. hispanicus and Lupinus luteus of Juno variety. In the seed of Lupinus pilosus the thickness of the seed coat was 1100 µm, while in Lupinus luteus it was 300 µm. The analysed Lupinus seeds accumulated from 73 mg/g d.m. (dry matter of seed embryo) to 155 mg of soluble sugars/g d.m. The highest quantity of oligosaccharides of the raffinose series was found in seeds of Lupinus luteus, while the lowest amount in seed of Lupinus palaestinus. Galactosyl cyclitols appeared in largest amount in seeds of Lupinus palaestinus and Lupinus pilosus, appropriately 41.93 and 33.75 mg/g dm. The lowest amount of galactosyl cyclitols appeared in Lupinus atlanticus, Lupinus cosentinii and Lupinus hispanicus

Cyclitols, galactosyl cyclitols and raffinose family oligosaccharides in Mexican wild lupin seeds

Ten to 16 ethanol-soluble carbohydrate components were identified in the seeds of six Mexican wild lupins. The analysed carbohydrates included: monosaccharides, disaccharides, cyclitols, galactosyl cyclitols and raffinose family oligosaccharides. Stachyose and sucrose were the main carbohydrate component in the Lupinus montanus, L. rotundiflorus, L. exaltatus, L. mexicanus and L. elegans seeds. Only trace quantities of verbascose were detected in Lupinus mexicanus seeds. The analysed seeds accumulated 38 to 78 mg/g d.m. carbohydrates. The raffinose family oligosaccharides constituted 41 to 85.2% of the identified carbohydrate component pool. The analysed Lupinus seeds contained 3 to 8 unidentified carbohydrate components

Morphological and biochemical characteristics of yellow lupin growing on soil contaminated with chlortetracycline in photoperiod and darkness

W ocenie zanieczyszczenia środowiska lekami bardzo ważną rolę odgrywają badania z wykorzystaniem roślin przeznaczonych na cele konsumpcyjne. Celem pracy było określenie fitotoksyczności chlorotetracykliny (0, 1,45, 2,90, 5,80, 11,60, 23,19 i 46,38 mg∙kg-1 gleby) obecnej w glebie wobec łubinu żółtego (Lupinus luteus L.) odmiany Mister. Oceniano wybrane cechy morfologiczne łubinu oraz biochemiczne aktywności peroksydazy i katalazy w korzeniach i łodygach siewek łubinu w warunkach fotoperiodu i ciemności. Stwierdzono, że niskie stężenia chlorotetracykliny w glebie nie zmieniają długości korzeni i łodyg. Ciśnienie osmotyczne siewek łubinu w obu wariantach świetlnych przy najwyższym stężeniu leku (46,38 mg∙kg-1 gleby) wzrosło około dwukrotnie w porównaniu z próbami kontrolnymi. Aktywność peroksydazy korzeni rosnących na glebie zawierającej lek w stężeniu 46,38 mgkg-1wyniosła 29 U (fotoperiod) i 24 U (ciemność). Aktywność katalazy była większa w łodygach łubinu żółtego rosnących w ciemności (15 U) w porównaniu do korzeni rosnących w tych samych warunkach świetlnych (12 U).Veterinary antibiotics are important measures for the treatment of diseases in production animals. However, the annual increase in their use in cattle and poultry production is disturbing.Tetracyclines, including tetracycline, chlortetracycline and oxytetracycline, are among the most commonly used antibiotics worldwide. Since they are poorly absorbed and excreted in substantial amounts in the digestive tract of animals (about 5080%) with faeces and urine, chlortetracycline, oxytetracycline and tetracycline are detected in manure and slurry. They are sensitive to light and are degraded by light and oxidative factors. The studies were conducted under photoperiodic conditions and constant darkness in order to establish whether solar light has an impact on the uptake of chlortetracycline by 8-day-old yellow lupin seedlings. In addition, it was investigated whether chlortetracycline in soil (under photoperiod or darkness) influences the activity of peroxidase and superoxide dismutase, i.e. the enzymes that neutralize free radicals, in yellow lupin roots and stems. Research using plants typically intended for consumption plays a very important role in the evaluation of environment contaminated with drugs. The aim of the study was to investigate the phytotoxicity low concentration of chlortetracycline (0, 1.45, 2.90, 5.80, 11.60, 23.19 and 46.38 mg-kg-1 of soil) to yellow lupin (Lupinus luteus L.) cv. Mister. Morphological characteristics and biochemical reactions (peroxidase and catalyze activities) yellow lupin seedlings growing in a photoperiod and in darkness were evaluated. It was found that chlo-rtetracycline was phytotoxic to yellow lupin. The average length of roots growing on soil contaminated with the tested concentrations of chlortetracycline was 76 mm (photoperiod) and 82 mm (darkness). Lupin produced significantly shorter roots compared to the control growing in darkness on soil contaminated with 1.45, 2.90, and 5.80 mg-kg-1 of soil. It was found that low concentrations of chlortetracycline in soil were not changed roots and stems length, and in contrast to the dark photoperiod to prolong the test organs. The osmotic pressure of lupin seedlings in both light conditions at the highest concentration of the drug (46.38 mg∙kg-1 of soil) was increased about twice compared with controls. Peroxidase activity was achieved the value of 29 U (photoperiod) and 24 U (dark) at the highest concentration of the drug (46.38 mg∙kg-1 of soil). Catalase activity was higher in the stems of yellow lupin grown in the dark (15 U) compared to the roots grown in the same conditions of light (12 U)