DIMAS Development of an integrated database for the management of accidental spills. Part 2. Global change, ecosystems and biodiversity - SPSDII: final report

DIMAS is a 2-year project executed by three Belgian partners (EURAS, VLIZ and Ghent University) and funded by the SPSD II research program of the Belgian Science Policy (BELSPO). Several shipping accidents in Belgian territorial waters, made the various government agencies involved aware of the need to develop tools to assess the risks and impact on marine resources in the case of an accidental release of hazardous substances. DIMAS aims at the protection of the North Sea and Western Scheldt in case of accidental spills from ships. In the present project, a relational database is developed, providing reliable, easy to interpret and up-to-date information on marine specific issues. The database contains the latest information on effects (acute and chronic), absorption, distribution, bioaccumulation/biomagnification, GESAMP hazard profiles and physico-chemical properties for a selection of priority substances and is publicly available (www.vliz.be/projects/dimas). The selection of the substances is based on criteria such as occurrence on priority lists, volumes transported over sea, frequency of involvement in accidental spills and frequency of transports over sea. The first beneficiaries of this database are the people directly involved in the first phase of a containment plan for an accidental spill. The final indirect beneficiaries are the general public (scientists, journalists, general public, etc.) who will be better informed about the potential impact to man and the environment

Endocrine disruption in the Scheldt estuary distribution, exposure and effects (ENDIS-RISKS). Final report

ENDIS-RISKS is a multidisciplinary, research project conducted by five institutes. This project aimed to assess the distribution, exposure and effects of endocrine disruptors in the Scheldt estuary, with specific attention to invertebrates. The Scheldt estuary is known to be one of the most polluted estuaries in the world. The industrial areas of Ghent and Antwerp are to a large extent responsible for this pollution. To achieve these goals detailed knowledge of the distribution and long-term effects of these substances is needed. This information is crucial for the development of future-oriented policy measures at the national and European level. The project can be divided into four different research phases. In Phase I the occurance and distribution of endocrine disrupting substances in the Scheldt estuary was studied. Water, sediment, suspended solids and biota were sampled 3 times a year for a period of 4 years (2002-2006). In all these matrices, 7 groups of chemicals were analysed: estrogens, pesticides, phthalates, organotins, polyaromatic components (PCBs, PBDEs), polyaromatic hydrocarbons (PAHs) and phenols. All the analyzed chemicals are on the OSPAR list of priority chemicals or are indicated as endocrine disruptors on this list. The different water samples were also tested using in vitro assays to assess their potential to bind to the (human) estrogen and androgen receptor. Phase II evaluated the exposure of biota occuring in the Scheldt estuary to endocrine disrupting substances. Based on the results of the chemical analysis, priority substances were selected. Phase III studied the effects of endocrine disrupting substances occurring in the Scheldt estuary on resident mysid shrimp populations (laboratory and field studies). Substances of concern were selected and tested in the laboratory to evaluate their effects on the estuarine mysid Neomysis integer. In the context of this project, three new assays using invertebrate-specific endpoints were developed to examine the effect of endocrine disrupting chemicals (EDCs) on molting, embryogenesis and vitellogenesis of N. integer. Finally, in Phase IV laboratory and field results were used to perform a preliminary environmental risk assessment of endocrine disruptors in the Scheldt estuary. Samples were collected along the salinity gradiënt of the Scheldt estuary with the RV Belgica. Water samples were taken with Teflon-coated Go-Flo bottles (10L), sediment samples with Van Veen Grab, biota with a hyperbentic sledge, and suspended particulate matter (SPM) was continuously sampled with an Alfa Laval flow-through centrifuge. For the chemical analysis, protocols were developed to analyse estrogens, organotriazine herbicides, organochlorine pesticides, phtalates, organotins, PAHs, PCBs, and PBDEs in the different matrices: i.e. water, sediment, SPM and biota.Experimental studies were performed to analyse growth, molting, embryogenesis and vitellogenesis of N. integer. These studies were needed to develop ecotoxicological assays to evaluate EDCs on these physiological processes. To study growth of N. integer, organisms were individually transferrred in exposure solutions and molts were collected to measure the growth after each molting. To study embryogenesis, embryos were taking out of the marsupium and placed in multiwell plates. Each day survival, developmental stages and hatching was analysed. To study vitellogenesis, vitellin was isolated from eggs with gelfitration and polyclonal antibodies were developed (in rabbits). With the isolated vitellin and the antibodies an enzyme-linked immunosorbent assay (ELISA) was developed. Vitellin was quatified in ovigerous females exposed to test compound in the laboratory and in females collected from the different sampling sites of the Scheldt estuary. In addition to vitellin levels, energy allocation and testosterone metabolism was examined in field collected mysids. Finally, results from population stu

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