AN ASSESSMENT OF THE PROPOSED NEW RISK MANAGEMENT PROGRAMS

The purpose of this assessment as outlined in the terms of reference is: "To obtain an assessment by an independent third party of the expected performance of the proposed new business risk management program's proposed New NISA and production insurance relative to the current set of risk management programming, including NISA, CFIP, crop insurance and companion programs." Within this context, the specific mandate and scope is to assess "the extent to which the current and proposed programs meet the objectives set out by Agriculture Ministers for business risk management programming, as follows: · to ensure programs are responsive to demand and that government dollars are directed to areas of need with respect to income stabilization, disaster mitigation, insurance coverage and investment; · to provide equal treatment for farmers across Canada facing similar risk situations; · to minimize the distortion of farmers' production and marketing decisions; · to focus on management of risks related to the stability of the entire farm and to avoid duplication of payments; · to be relatively simple and easy to understand; and · to facilitate long term planning by farmers."Risk and Uncertainty,

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

AN ASSESSMENT OF THE PROPOSED NEW RISK MANAGEMENT PROGRAMS

The purpose of this assessment as outlined in the terms of reference is: "To obtain an assessment by an independent third party of the expected performance of the proposed new business risk management program's proposed New NISA and production insurance relative to the current set of risk management programming, including NISA, CFIP, crop insurance and companion programs." Within this context, the specific mandate and scope is to assess "the extent to which the current and proposed programs meet the objectives set out by Agriculture Ministers for business risk management programming, as follows: · to ensure programs are responsive to demand and that government dollars are directed to areas of need with respect to income stabilization, disaster mitigation, insurance coverage and investment; · to provide equal treatment for farmers across Canada facing similar risk situations; · to minimize the distortion of farmers' production and marketing decisions; · to focus on management of risks related to the stability of the entire farm and to avoid duplication of payments; · to be relatively simple and easy to understand; and · to facilitate long term planning by farmers.

Trabecular bone adaptation to low-magnitude high-frequency loading in microgravity

Exposure to microgravity causes loss of lower body bone mass in some astronauts. Low-magnitude high-frequency loading can stimulate bone formation on earth. Here we hypothesized that low-magnitude high-frequency loading will also stimulate bone formation under microgravity conditions. Two groups of six bovine cancellous bone explants were cultured at microgravity on a Russian Foton-M3 spacecraft and were either loaded dynamically using a sinusoidal curve or experienced only a static load. Comparable reference groups were investigated at normal gravity. Bone structure was assessed by histology, and mechanical competence was quantified using μCT and FE modelling; bone remodelling was assessed by fluorescent labelling and secreted bone turnover markers. Statistical analyses on morphometric parameters and apparent stiffness did not reveal significant differences between the treatment groups. The release of bone formation marker from the groups cultured at normal gravity increased significantly from the first to the second week of the experiment by 90.4% and 82.5% in response to static and dynamic loading, respectively. Bone resorption markers decreased significantly for the groups cultured at microgravity by 7.5% and 8.0% in response to static and dynamic loading, respectively. We found low strain magnitudes to drive bone turnover when applied at high frequency, and this to be valid at normal as well as at microgravity. In conclusion, we found the effect of mechanical loading on trabecular bone to be regulated mainly by an increase of bone formation at normal gravity and by a decrease in bone resorption at microgravity. Additional studies with extended experimental time and increased samples number appear necessary for a further understanding of the anabolic potential of dynamic loading on bone quality and mechanical competence.ISSN:1932-620

ProCI (µM) released by each bone sample.

<p>ProCI (µM) released by each sample in the culture medium during the first week (medium analyzed at the 6^th day) and the second week (medium analyzed at the 12^th day) of the experiment for the four groups of samples. A) Data relative to the samples dynamically loaded at microgravity; B) Data relative to the samples statically loaded at microgravity; C) Data relative to the samples dynamically loaded at normal gravity; D) Data relative to the samples statically loaded at normal gravity. ^a<i>p</i><0.05, n = 6. ^b<i>p</i><0.05, n = 5 (sample ‘10G’ is an outlier and was excluded for statistical analyses).</p

Label penetration depth at two penetration sites (from lower and upper surfaces, and from circumference edge).

<p>Calcein green penetration, which can be defined as time point zero, was significantly increased (*<i>p</i><0.01) compared to the alizarin complexon penetration (end time point). Box plots show the median line, the 25% and the 75% quartiles which define the box, the 1.5x interquartile-range whiskers, as well as outliers (○).</p

Bone structure and mechanical competence for the 4 groups of samples.

<p>Morphometric parameters (BV/TV  =  bone volume fraction, BS/TV  =  bone surface density, Tb.Th.  =  trabecular thickness, Tb.N.  =  trabecular number, Tb.Sp.  =  trabecular separation, Conn. D.  =  connectivity density, SMI  =  structure model index) and calculated apparent Young's modulus (E app) for the 4 groups of samples are indicated. No statistical differences were found. Values are expressed as mean ± standard deviation (n = 6 samples/group).</p