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

Tropical Eastern Pacific Records of the Prickly Shark, Echinorhinus cookei (Chondrichthyes: Echinorhinidae)

v. ill. 23 cm.Also available through BioOne: http://www.bioone.org/doi/abs/10.2984/65.4.433QuarterlyMost records of the prickly shark, Echinorhinus cookei Pietschmann, 1928, are from temperate and subtropical areas of the Pacific rim, with few records from the tropics. This seemingly disjunct distribution led some authors to consider E. cookei to have an antitropical distribution. Unreported museum specimens and underwater observations of E. cookei from Cocos Island, Costa Rica; the Galápagos Islands; and northern Peru confirm its occurrence in the tropical eastern Pacific and, combined with other published records from the eastern Pacific, establish a continuous, panhemispheric eastern Pacific distribution

New data on fish diet and bone digestion of the Eurasian otter (Lutra lutra) (Mammalia: Mustelidae) in central France

Fish remains are abundant and easily recognizable in many archaeological sites. The origin of such assemblages is generally poorly known. The ability to create small fish bone accumulations is restricted to a small number of predators (including raptors, carnivores and humans). In order to recognize the agents responsible for these concentrations in archaeological sites, we have investigated the taphonomy of the fish remains from otter spraints to determine the potential role of the Eurasian otter, Lutra lutra, in the formation of fossil assemblages as a piscivorous mammal. Currently, few data are available to characterize the accumulation of otter remains in natural or archaeological sites. We analyzed a collection of 29 otter spraints from Bugeat (Corrèze) in central France. We identified the remains of eight fish species: brown trout (Salmo trutta, Salmonidae), perch (Perca fluviatilis, Percidae), pumpkinseed (Lepomis gibbosus, Centrarchidae), and several Cyprinidae, rudd (Scardinius erythrophthalmus), minnow (Phoxinus phoxinus), bullhead (Cottus gobio), and the indeterminate pair chub/dace (Squalius cephalus/Leuciscus leuciscus). The species and the body parts present, along with the reconstruction of the fish weight and observations of any modifications, such as deformation, rounding and polishing, give us insight into otter prey categories and their transformation after digestion. Among the ca. 200 bones constituting the whole fish skeleton, only between six and 39 bones survived depending on the different species. Cyprinids display a high-moderate digestion grade and seem to be the taxon most affected by digestion (64.67%). Based on surface modifications, such as breakage and digestion traces, as well as bone element representation, we produced a set of criteria as a new tool to be applied to the fossil record

Fishing at Arapus-Mangaasi, Efate, Vanuatu (2800-2200 BP): new methodological approaches and results

International audienceThe Arapus-Mangaasi site, located on the north-west coast of the island of Efate, Vanuatu, and first settled around 2800 BP, was excavated between 1999 and 2003 within the framework of a joint Australian National University-Vanuatu National Museum research and training program. The site yielded not only a range of cultural material that allowed the re-interpretation of the Central Vanuatu ceramic sequence but also well-preserved faunal remains, including a substantial number of fish bones. The present study focuses on the analysis of the ichthyofauna recovered in the area of Arapus and on the assessment of the most efficient identification protocol with a view to obtain precise faunal data leading to the characterisation of the fishing economy. Out of a total of 8080 fish remains, 2387 were taxonomically identified. The general assemblage is composed of 23 families of marine fishes, belonging to the Teleostei and Elasmobranchii groups, and dominated by surgeonfishes (Acanthuridae), parrotfishes (Scaridae), and groupers (Serranidae). The study of vertebrae allowed the identification of most acanthurids and hence proved to be essential in obtaining a detailed inventory of the fish spectrum. The assemblage composition highlights the presence of a large variety of inshore and reef-associated taxa, likely to have been caught by means of polyvalent and broad-spectrum fishing gear, possibly mass capturing devices, such as nets or traps, combined with angling and/or spearing. The results also suggest an opportunistic exploitation of ichthyofaunal resources during the Arapus period (2800 BP) and a probable decrease in the consumption of fish from the beginning of the Erueti period (2800–2200 BP) onwards

Potential for combined use of parasitoids and generalist predators for biological control of the key invasive tomato pest Tuta absoluta

The tomato leafminer Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) has recently invaded Mediterranean countries and is a major pest in tomato crops. Trichogrammatid oophagous parasitoids have shown promising potential for controlling the pest before the yield decreases in the greenhouse. In protected tomato crops (greenhouse), mirid predators are commonly used for biological control of whiteflies and they also prey on T. absoluta. These predators do not attack Trichogramma adults but they may partially decrease the overall impact of parasitoids on T. absoluta if intraguild predation (IGP) occurs on parasitized eggs. Under laboratory conditions, we tested if the mirid predator Macrolophus pygmaeus shows preference between parasitized and unparasitized T. absoluta eggs. We also tested if the predator reduces the number of parasitized eggs on caged tomato plants (microcosms) and assessed the efficacy of natural enemies used alone or together in limiting T. absoluta populations. We found that IGP is inflicted on the parasitoid Trichogramma achaeae by M. pygmaeus and that the risk of IGP depends on the developmental stage of T. achaeae inside the egg because the larva is at risk mostly early in its development (when parasitized egg is still yellow). In addition, we observed that non-consumptive events, likely probing of the predator on parasitized eggs, may induce mortality in parasitoid offspring without actual feeding on parasitized eggs. However, both IGP and non-consumptive events decreased when the predator was not confined with parasitized eggs in small arenas. Despite negative effects of the predator to the parasitoid, results demonstrate that adding Trichogramma parasitoids may significantly increase the level of control of the pest over what could be attained when only the mirid predator M. pygmaeus is present on tomato. Implications of results are discussed regarding potential of these natural enemies for biological control of T. absoluta in greenhouse tomato crops. ♦ 2013 Springer-Verlag Berlin Heidelberg

Thermal biology of Tuta absoluta: demographic parameters and facultative diapause

The South American tomato pinworm, Tuta absoluta, (SATP) is now a devastating pest worldwide of crops in the family Solanaceae. Most prior studies of SATP’s thermal biology were based on populations from tropical regions, and proved unsuitable for explaining its invasion of large areas of the Palearctic. A more holistic approach to the analysis of its thermal biology is essential background for developing models to assess its invasive potential. Our studies found that SATP has lower and upper thermal thresholds (θL = 5.37&nbsp;°C and θU = 35.69&nbsp;°C, respectively) than South American populations used in prior studies (θL = 7.38&nbsp;°C and θU = 33.82&nbsp;°C). Age-specific life tables were used to estimate the effects of temperature on its demographic parameters. Diapause in SATP had not been characterized prior to our study. We found facultative diapause in pupae developing from larvae exposed to relatively low temperatures (i.e., 2 and 5&nbsp;°C) and short-day length for different exposure periods. The strength of diapause was measured as an increase in post-treatment developmental times of pupae (i.e., degree days) that on average were 2.45–3-fold greater than of pupae reared at favorable temperatures. A lower developmental threshold and a facultative diapause increase the invasive potential of SATP in temperate areas. Knowledge of this thermal biology is essential for predicting the potential geographic spread of this pest and to develop management and control strategies

Impact of low temperature and host plant on Tuta absoluta

Alternative host plants are among the key factors influencing the spread of invasive pests because they are utilized as a food source and provide shelter in unfavorable conditions. The South American tomato pinworm (SATP), Tuta absoluta Meyrick (Lepidoptera: Gelechiidae), has a high behavioral and physiological plasticity enabling it to rapidly spread in several countries. Among the multiple strategies used by SATP in the invasion process is the use of alternative host plants including black nightshade (BNS), Solanum nigrum L. (Solanaceae), a perennial plant widely distributed across all habitats worldwide. Besides the life table and behavioral parameters of SATP on tomato, its survival and reproduction in low temperatures on alternative host plants should be assessed to evaluate the likely spread in temperate regions with harsh winters. In our study, comparing solanaceous species through generations, the primary difference was in the mean generation time with SATP reared on BNS, whereby it had a longer development time than larvae and pupae reared on tomato plants. Adults preferred tomato plants even if they had been reared as larvae on BNS. Exposure periods of 7, 14, and 21&nbsp;days to 4 °C indicated that more than 50% of SATP pupae reared on BNS plants survived more than 14&nbsp;days. The survival of SATP reared on tomato plants exceeded 21&nbsp;days and after exposure to 4 °C, females reared on both plants remained fertile. The life table and behavioral parameters recorded demonstrated a significant potential of BNS to support the development of SATP, also at low temperature. Therefore, even with effective border surveillance and phytosanitation processes in place, invasion through an alternative host is possible and difficult to detect