Cost-Effectiveness of Icosapent Ethyl (IPE) for the Reduction of the Risk of Ischemic Cardiovascular Events in Canada.

Background: Despite the use of statins, many patients with cardiovascular disease (CVD) have persistent residual risk. In a large Phase III trial (REDUCE-IT), icosapent ethyl (IPE) was shown to reduce the first occurrence of the primary composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina. Methods: We conducted a cost-utility analysis comparing IPE to placebo in statin-treated patients with elevated triglycerides, from a publicly funded, Canadian healthcare payer perspective, using a time-dependent Markov transition model over a 20-year time horizon. We obtained efficacy and safety data from REDUCE-IT, and costs and utilities from provincial formularies and databases, manufacturer sources, and Canadian literature sources. Results: In the probabilistic base-case analysis, IPE was associated with an incremental cost of $12,523 and an estimated 0.29 more quality-adjusted life years (QALYs), corresponding to an incremental cost-effectiveness ratio (ICER) of $42,797/QALY gained. At a willingness-to-pay of $50,000 and $100,000/QALY gained, there is a probability of 70.4% and 98.8%, respectively, that IPE is a cost-effective strategy over placebo. The deterministic model yielded similar results. In the deterministic sensitivity analyses, the ICER varied between $31,823-$70,427/QALY gained. Scenario analyses revealed that extending the timeframe of the model to a lifetime horizon resulted in an ICER of $32,925/QALY gained. Conclusion: IPE represents an important new treatment for the reduction of ischemic CV events in statin-treated patients with elevated triglycerides. Based on the clinical trial evidence, we found that IPE could be a cost-effective strategy for treating these patients in Canada.

Autonomic nervous system assessment using heart rate variability.

The role of the autonomic nervous system in the onset of supraventricular and ventricular arrhythmias is well established. It can be analysed by the spontaneous behaviour of the heart rate with ambulatory ECG recordings, through heart rate variability measurements. Input of heart rate variability parameters into artificial intelligence models to make predictions regarding the detection or forecast of rhythm disorders is becoming routine and neuromodulation techniques are now increasingly used for their treatment. All this warrants a reappraisal of the use of heart rate variability for autonomic nervous system assessment.Measurements performed over long periods such as 24H-variance, total power, deceleration capacity, and turbulence are suitable for estimating the individual basal autonomic status. Spectral measurements performed over short periods provide information on the dynamics of systems that disrupt this basal balance and may be part of the triggers of arrhythmias, as well as premature atrial or ventricular beats. All heart rate variability measurements essentially reflect the modulations of the parasympathetic nervous system which are superimposed on the impulses of the adrenergic system. Although heart rate variability parameters have been shown to be useful for risk stratification in patients with myocardial infarction and patients with heart failure, they are not part of the criteria for prophylactic implantation of an intracardiac defibrillator, because of their high variability and the improved treatment of myocardial infarction. Graphical methods such as Poincaré plots allow quick screening of atrial fibrillation and are set to play an important role in the e-cardiology networks. Although mathematical and computational techniques allow manipulation of the ECG signal to extract information and permit their use in predictive models for individual cardiac risk stratification, their explicability remains difficult and making inferences about the activity of the ANS from these models must remain cautious.

Integration of 3D nuclear imaging in 3D mapping system for ventricular tachycardia ablation in patients with implanted devices: Perfusion/voltage retrospective assessment of scar location.

Background: The identification of low-voltage proarrhythmic areas for catheter ablation of scar-mediated ventricular tachycardia (VT) remains challenging. Integration of myocardial perfusion imaging (single-photon emission computed tomography/computed tomography; SPECT/CT) and electroanatomical mapping (EAM) may improve delineation of the arrhythmogenic substrate. Objective: To assess the feasibility of SPECT/CT image integration with voltage maps using the EnSite Precision system (Abbott) in patients undergoing scar-mediated VT ablation. Methods: Patients underwent SPECT/CT imaging prior to left ventricular (LV) EAM with the EnSite Precision mapping system. The SPECT/CT, EAM data, and ablation lesions were retrospectively co-registered in the EnSite Precision system and exported for analysis. Segmental tissue viability scores were calculated based on SPECT/CT perfusion and electrogram bipolar voltage amplitude. Concordance, specificity, and sensitivity between the 2 modalities as well as the impact of SPECT/CT spatial resolution were evaluated. Results: Twenty subjects (95% male, 67 ± 7 years old, left ventricular ejection fraction 36% ± 11%) underwent EAM and SPECT/CT integration. A concordance of 70% was found between EAM and SPECT/CT for identification of cardiac segments as scar vs viable, with EAM showing a 68.5% sensitivity and 76.4% specificity when using SPECT/CT as a gold standard. Projection on low-resolution 3D geometries led to an average decrease of 38% ± 22% of the voltage points used. Conclusion: The study demonstrated the feasibility of integrating SPECT/CT with EAM performed retrospectively for characterization of anatomical substrates during VT ablation procedures.

Cost-Effectiveness Analysis of Evolocumab in Adult Patients with Atherosclerotic Cardiovascular Disease in Canada.

INTRODUCTION: To evaluate the cost-effectiveness of evolocumab when added to standard of care lipid-lowering treatment (LLT) for patients with atherosclerotic cardiovascular disease (ASCVD) who cannot adequately control their low-density lipoprotein cholesterol (LDL-C) despite optimized LLT in Canada. METHODS: An incremental cost-utility analysis was conducted using a Markov cohort state transition model adapted to the Canadian setting. Analyses were conducted from a public health and societal perspective using a lifetime time horizon for Canada. Scenario analyses were conducted on the basis of recommendations from the 2021 Canadian Cardiovascular Society (CCS) dyslipidemia guidelines. RESULTS: In ASCVD patients with prior myocardial infarction (MI) and baseline LDL-C ≥ 1.8 mmol/L, adding evolocumab to optimized statin therapy with or without ezetimibe is associated with an incremental cost per quality-adjusted life year (QALY) gained of $66,453 CAD. Furthermore, for every 100 patients treated with evolocumab for lifetime, adding evolocumab to optimized LLT will prevent approximately 52 cardiovascular (CV) events, of which seven would be fatal. The results are generally robust using univariate and simultaneous variation in model input parameters. Scenario analyses for patient populations as per the CCS guidelines suggest that evolocumab added to optimized LLT may be considered cost-effective, given an incremental cost-effectiveness ratio (ICER) threshold of CAD$100,000 per QALY gained. Limitations associated with this analysis should be interpreted in the context of data and modeling assumptions used. CONCLUSION: Overall, this analysis supports reimbursement of evolocumab by payers in patients with ASCVD who cannot reach LDL-C thresholds despite optimized LLT to reduce unnecessary fatal and non-fatal CV events.

Cost-effectiveness of low-dose colchicine after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT).

AIMS: In the randomized, placebo-controlled Colchicine Cardiovascular Outcomes Trial (COLCOT) of 4745 patients enrolled within 30 days after myocardial infarction (MI), low-dose colchicine (0.5 mg once daily) reduced the incidence of the primary composite endpoint of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization. To assess the in-trial period and lifetime cost-effectiveness of low-dose colchicine therapy compared to placebo in post-MI patients on standard-of-care therapy. METHODS AND RESULTS: A multistate Markov model was developed incorporating the primary efficacy and safety results from COLCOT, as well as healthcare costs and utilities from the Canadian healthcare system perspective. All components of the primary outcome, non-cardiovascular deaths, and pneumonia were included as health states in the model as both primary and recurrent events. In the main analysis, a deterministic approach was used to estimate the incremental cost-effectiveness ratio (ICER) for the trial period (24 months) and lifetime (20 years). Over the in-trial period, the addition of colchicine to post-MI standard-of-care treatment decreased the mean overall per-patient costs by 47%, from $502 to $265 Canadian dollar (CAD), and increased the quality-adjusted life years (QALYs) from 1.30 to 1.34. The lifetime per-patient costs were further reduced (69%) and QALYs increased with colchicine therapy (from 8.82 to 11.68). As a result, both in-trial and lifetime ICERs indicated colchicine therapy was a dominant strategy. CONCLUSION: Cost-effectiveness analyses indicate that the addition of colchicine to standard-of-care therapy after MI is economically dominant and therefore generates cost savings.

Hypertension Canada's 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children.

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy.

Measuring adherence to oral antidiabetic multi-drug treatment: Comparative validity of prescription claims-based adherence measures against hospitalization.

BACKGROUND: The use of prescription claims data to measure adherence to diabetes treatment is very common in research. However, there is no clear evidence regarding the accuracy of the methods used to assess adherence to multi-drug treatments for the many patients using multiple antidiabetic drugs. PURPOSE: To assess the validity of prescription claims-based adherence measures in the context of multiple oral antidiabetic drug treatment. METHODS: A cohort of patients who began their antidiabetic drug treatment with at least two oral antidiabetic drugs (new users) was created using Quebec medico-administrative data. Four different prescription claims-based adherence measures were assessed: proportion of days covered (PDC) by at least one class of drugs, mean PDC, PDC by all classes and daily polypharmacy possession ratio (DPPR). All-cause and diabetes-related hospitalizations were the validation criteria. To assess the validity of the measures, receiver operating characteristic (ROC) curves were plotted for each measure and each criterion. RESULTS: A total of 5982 individuals were included. The areas under the ROC curves for the PDC by at least one class of drugs, the mean PDC, the PDC by all classes of drugs and the DPPR were respectively 0.54 (95% CI: 0.52-0.56), 0.51 (0.49-0.53), 0.50 (0.48-0.52) and 0.51 (0.49-0.53) with all-cause hospitalization as criterion and 0.55 (0.53-0.57), 0.53 (0.51-0.55), 0.51 (0.49-0.53) and 0.53 (0.51-0.55) using diabetes-related hospitalization as criterion. CONCLUSIONS: The results suggest that all measures have poor validity in predicting hospitalizations thus raising concerns about their utility in the assessment of adherence to multi-drug treatment. Future research should assess the capacity of these measures to predict other outcomes more closely related to medication adherence.

Assessment of left ventricular ejection fraction with cardiofocal collimators: Comparison between IQ-SPECT, planar equilibrium radionuclide angiography, and cardiac magnetic resonance.

BACKGROUND: IQ-SPECT has been shown to significantly reduce acquisition time and administered dose while preserving image quality in myocardial perfusion imaging. Whether IQ-SPECT provides accurate left ventricular ejection fractions (LVEF) with gated blood pool SPECT (GBPS) remains unknown. METHODS: Sixty patients underwent IQ-SPECT GBPS and planar imaging. Among those patients, 11 underwent both cMRI and GBPS. GBPS LVEF, LVEDV, and LVESV were calculated using 2 validated software; QBS (Cedars-Sinai Medical Center, Los Angeles, USA) and MHI (Montreal Heart Institute, Montreal, Canada). LVEF, LVEDV, and LVESV obtained with the different modalities were compared. RESULTS: Average planar LVEF was 48 ± 11% (mean ± SD), average LVEDV was 177 ± 59 mL (range 63 to 342 mL), and average LVESV was 96 ± 46 mL (range 16 to 234 mL). GBPS LVEF and their correlation coefficient with planar LVEF were 40 ± 12% (r = 0.70) and 44 ± 12% (r = 0.83) with QBS and MHI, respectively. Correlation coefficient between cMRI and planar LVEF was 0.65 and were 0.69 and 0.52 between cMRI and GBPS using QBS and MHI, respectively. CONCLUSIONS: LVEF calculated with GBPS using IQ-SPECT correlates with planar measurements. Correlation is best using the MHI method and variation is independent of LVEDV.

Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

Neighbourhood Material and Social Deprivation and Exposure to Antidepressant Drug Treatment: A Cohort Study Using Administrative Data.

OBJECTIVE: To assess whether neighbourhood deprivation is associated with exposure to an antidepressant drug treatment (ADT) and its quality among individuals diagnosed with unipolar depression and insured by the Quebec public drug plan. METHOD: We conducted an administrative database cohort study of adults covered by the Quebec public drug plan who were diagnosed with a new episode of unipolar depression. We assessed material and social deprivation using an area-based index. We considered exposure to an ADT as having ≥1 claim for an ADT within the 365 days following depression diagnosis. Among those exposed to ADT, ADT quality was assessed with 3 indicators: first-line recommended ADT, persistence with the ADT, and compliance with the ADT. Generalized linear models were used to estimate adjusted prevalence ratios (aPR) and 95% confidence intervals (95% CI). RESULTS: Of 100,432 individuals with unipolar depression, 65,436 (65%) were exposed to an ADT in the year following the diagnosis. Individuals living in the most materially deprived areas were slightly more likely to be exposed to an ADT than those living in the least deprived areas (aPR, 1.04; 95% CI, 1.03 to 1.06). The likelihoods of being exposed to a first-line ADT, persisting for the minimum recommended duration and complying with the ADT were independent of the deprivation levels. CONCLUSIONS: Neighbourhood deprivation was not associated with ADT quality among individuals insured by the Quebec public drug plan. It might be partly attributable to the public drug plan whose goal is to provide equitable access to prescription drugs regardless of income.

Guidance on quantitative pest risk assessment.

This Guidance describes a two-phase approach for a fit-for-purpose method for the assessment of plant pest risk in the territory of the EU. Phase one consists of pest categorisation to determine whether the pest has the characteristics of a quarantine pest or those of a regulated non-quarantine pest for the area of the EU. Phase two consists of pest risk assessment, which may be requested by the risk managers following the pest categorisation results. This Guidance provides a template for pest categorisation and describes in detail the use of modelling and expert knowledge elicitation to conduct a pest risk assessment. The Guidance provides support and a framework for assessors to provide quantitative estimates, together with associated uncertainties, regarding the entry, establishment, spread and impact of plant pests in the EU. The Guidance allows the effectiveness of risk reducing options (RROs) to be quantitatively assessed as an integral part of the assessment framework. A list of RROs is provided. A two-tiered approach is proposed for the use of expert knowledge elicitation and modelling. Depending on data and resources available and the needs of risk managers, pest entry, establishment, spread and impact steps may be assessed directly, using weight of evidence and quantitative expert judgement (first tier), or they may be elaborated in substeps using quantitative models (second tier). An example of an application of the first tier approach is provided. Guidance is provided on how to derive models of appropriate complexity to conduct a second tier assessment. Each assessment is operationalised using Monte Carlo simulations that can compare scenarios for relevant factors, e.g. with or without RROs. This document provides guidance on how to compare scenarios to draw conclusions on the magnitude of pest risks and the effectiveness of RROs and on how to communicate assessment results.

Pest risk assessment of Spodoptera frugiperda for the European Union.

EFSA was asked for a partial risk assessment of Spodoptera frugiperda for the territory of the EU focussing on the main pathways for entry, factors affecting establishment, risk reduction options and pest management. As a polyphagous pest, five commodity pathways were examined in detail. Aggregating across these and other pathways, we estimate that tens of thousands to over a million individual larvae could enter the EU annually on host commodities. Instigating risk reduction options on sweetcorn, a principal host, reduces entry on that pathway 100-fold. However, sweetcorn imports are a small proportion of all S. frugiperda host imports, several of which are already regulated and further regulation is estimated to reduce the median number entering over all pathways by approximately 10%. Low temperatures limit the area for establishment but small areas of Spain, Italy and Greece can provide climatic conditions suitable for establishment. If infested imported commodities are distributed across the EU in proportion to consumer population, a few hundreds to a few thousands of individuals would reach NUTS 2 regions within which suitable conditions for establishment exist. Although S. frugiperda is a known migrant, entry directly into the EU from extant populations in sub-Saharan Africa is judged not feasible. However, if S. frugiperda were to establish in North Africa, in the range of thousands to over two million adults could seasonally migrate into the southern EU. Entry into suitable NUTS2 areas via migration will be greater than via commercial trade but is contingent on the establishment of S. frugiperda in North Africa. The likelihood of entry of the pest via natural dispersal could only be mitigated via control of the pest in Africa. If S. frugiperda were to arrive and become a pest of maize in the EU, Integrated Pest Management (IPM) or broad spectrum insecticides currently used against existing pests could be applied.

Factors associated with antidiabetic medication non-adherence in patients with incident comorbid depression.

AIM: To identify factors associated with antidiabetic drug (AD) non-adherence among patients with type 2 diabetes and depression. STUDY DESIGN AND SETTINGS: We conducted a population-based retrospective cohort study among new AD users with a diagnosis of depression following AD initiation. We used public health insurance data from Quebec. The dependent variable was non-adherence (i.e., <90% of days covered by ≥1AD) in the year after a depression diagnosis. Different sociodemographic, clinical and medication-related variables were assessed as potential factors of non-adherence to AD treatment. We performed univariate and multivariate logistic regressions. RESULTS: We identified 3106 new users of ADs with a diagnosis of depression between 2000 and 2006. Of these individuals, 52% were considered non-adherent to their ADs. Baseline non-adherence, younger age, the addition of another AD to the initial treatment, <4 drug claims, visits with several different physicians, high socioeconomic status, and a small number of diabetes complications were associated with AD non-adherence. CONCLUSIONS: The factors identified in the present study may help clinicians recognize patients with type 2 diabetes and incident depression at increased risk for non-adherence. In these patients, close follow-up and targeted interventions could help improve adherence to AD treatment, improve glycemic control and reduce complications.

Pest risk assessment of Eotetranychus lewisi for the EU territory.

Following the 2014 EFSA's Panel on Plant Health scientific opinion on the pest categorisation of the spider mite Eotetranychus lewisi, the European Commission requested the Panel to perform a pest risk assessment and evaluate the risk reduction options. A stochastic model was used to assess entry, establishment and spread and related uncertainties. In the EU, E. lewisi has only been reported to occur in Portugal (Madeira). Entry pathways assessed were strawberry plants for planting from the USA, poinsettia and raspberry plants for planting, and orange and lemon fruits from third countries. Entry is most likely via poinsettia. Under current EU phytosanitary requirements, there is around a one in ten chance that E. lewisi will establish outdoors over the next 10 years. Although unlikely, establishment would most likely occur in southern Europe where environmental conditions, temperature and host density, are most suitable. If E. lewisi did establish, pest spread is expected to be mainly human assisted, most likely the mite being transported long distances on plants for planting. Nevertheless, while remaining a regulated pest, spread would be slow and most likely confined to one NUTS 2 area after 10 years. Under a scenario with enhanced measures (pest free place of production) at origin, the Panel's assessment indicate that it is extremely unlikely that E. lewisi would establish within 10 years hence spread is also extremely unlikely. The absence of trade of host plants from Madeira to other parts of the EU could explain why E. lewisi has not spread to other EU Member States. E. lewisi is reported as reducing yield and quality of peaches and poinsettia and is regarded as a growing concern for strawberry and raspberry growers in the Americas. The Panel concludes that should E. lewisi be introduced in the EU similar impacts could be expected.

Pest risk assessment of Atropellis spp. for the EU territory.

Following a request from the European Commission, the EFSA Plant Health (PLH) Panel performed a risk assessment for Atropellis spp. in the EU focusing on the risk of entry, the host range and the potential impacts. Atropellis is a fungal pathogen of several Pinus spp. in North America. The pathogen has not been reported from Europe and is a quarantine pest regulated in Annex IIAI of Council Directive 2000/29/EC on plants (other than fruit and seeds), isolated bark and wood of Pinus. The main pathways of entry considered were Pinus plants, wood and isolated bark. Given the ban of importing Pinus plants from outside Europe into the EU and the lack of information on EU imports of isolated Pinus bark, only the wood pathway was assessed quantitatively. The conclusion of the assessment of entry for scenario A0 (current regulatory situation) is that the risk of entry of Atropellis spp. is close to zero. This conclusion is expected to apply also in the case of removing the specific Atropellis regulations, because of the remaining generic Pinus requirements, as well as in a scenario with additional risk reduction options. The uncertainty associated with this assessment is relatively limited, given that all the quartiles of the estimated distribution of the number of potential founder populations are close to zero. For the North American Pinus spp. known to be susceptible and widely planted in the EU (mainly P. contorta and P. strobus), the damage observed in North America (loss of wood quality, stem deformations, mortality in young stands, environmental consequences) is expected in the EU to a similar (or higher) degree, should the pathogen be introduced. Similar impacts are expected on the European Pinus spp. known to be host of Atropellis spp. These include widespread and locally abundant species such as P. nigra, P. sylvestris and P. pinaster. There are, however, large uncertainties associated with this impact assessment due to the unknown susceptibility of several other Pinus spp. present in Europe. There is a need for research on the susceptibility to Atropellis spp. of those European Pinus spp.

Pest risk assessment of Radopholus similis for the EU territory.

The Panel on Plant Health performed a pest risk assessment on Radopholus similis, the burrowing nematode for the EU. The quantitative assessment focused on entry, establishment, spread and impact on tropical and subtropical ornamental host plants, the main pathways for entry of R. similis into the EU. Infested consignments are expected to enter the risk assessment area on ornamentals under all scenarios. For citrus, which is a closed pathway for entry, outdoor establishment was assessed. Establishment may only take place after successful transfer from ornamental plants to citrus production systems. This event is called 'shift' in this assessment, to indicate that this is an unusual transfer. It has been estimated that establishment of this nematode in the open field in the EU citrus production areas under current temperatures is possible in most parts of the citrus production area in the EU. Temperature conditions will prevent the nematode from establishing only in the northernmost citrus areas and at higher altitudes in the south. Host plants for planting originating from infested places of production (greenhouses) within the risk assessment area are considered the main pathway for spread within the risk assessment area. Under current climatic conditions, the population of R. similis is not expected to reach damaging population levels in the open field. In case of increased temperatures due to global warming, the nematode population may reach damaging levels in very few places outdoors. Currently, main impact is considered for ornamental greenhouse production in the risk assessment area. Impact will be either caused by direct plant growth reductions or loss due to phytosanitary measures applied on regulated plants. Despite the fact that R. similis is globally considered as one of the most destructive plant parasitic nematodes, the impact in the risk assessment area is considered low.

Pest risk assessment of Diaporthe vaccinii for the EU territory.

As requested by the European Commission, the EFSA Panel on Plant Health (PLH) Panel assessed the risk of Diaporthe vaccinii in the EU, focusing on entry, establishment, spread and impacts on cultivated and wild Vaccinium species, the principal hosts being American and European cranberry and blueberry. Several outbreaks occurred in the EU since 1956, but most were eradicated except in Latvia. The Panel considered entry via fruits and plants for planting. The risk of establishment from discarded infected berries is much lower than from infected plants for planting, of which, potted plants and cuttings pose the greatest risk, while plug plants, derived from tissue culture and grown in pest free structures, pose a low risk. Nine per cent of the EU is highly suitable for establishment of the pathogen, mostly in the SE and NE. Following establishment, the pathogen could spread naturally over short range, and by human assistance over long range. Calculations with an integrated model for entry, establishment and spread, indicate that with current regulations, over a period of 5 years, a few hundred cultivated Vaccinium plants and several thousand Vaccinium plants in natural ecosystems would contract the disease. The associated loss of commercial production is small, less than one tonne of berries per year. On natural vegetation, the median impact after 5 years was estimated to be negligible affecting a negligible proportion of the natural Vaccinium population (2 × 10-8). However, the uncertainty of this estimate was high, due to uncertainty about the rate of spread; in a worst-case scenario (99th percentile), almost 1% of plants in natural areas would become infected. Complete deregulation (scenario A1) was predicted to increase the impact substantially, especially in natural areas, while additional measures (scenario A2) would effectively eliminate the entry of infected plants for planting, further reducing the impacts below the current situation.

Incidence of Depression and Associated Factors in Patients With Type 2 Diabetes in Quebec, Canada: A Population-Based Cohort Study.

It has been reported that the risk of depression is higher among people with type 2 diabetes compared with a nondiabetic population. Among diabetic patients, depression has been associated with worse self-care behaviors, poor glycemic control, and an increased risk of diabetes complications. Identifying factors associated with the occurrence of depression may help physicians identify earlier diabetic patients at a high risk of developing depression, improve prevention, and accelerate proper treatment. To our knowledge, very few population-based studies have reported on the incidence of clinically diagnosed depression as a consequence of type 2 diabetes over a long follow-up period. The objective of this study was to estimate the incidence of clinically diagnosed depression among type 2 diabetic patients newly treated with oral antidiabetic drugs (ADs) and to identify factors associated with the occurrence of depression.Administrative claims data from the public health insurance plan were used to identify a cohort of new oral AD users aged ≥18 years between 2000 and 2006. Patients were followed from oral AD treatment initiation until the diagnosis of depression, ineligibility for the public drug plan, death, or the end of the study, whichever came first. Incidence rates were determined using person-time analysis. Factors associated with depression were identified using multivariable Cox regression analysis.We identified 114,366 new oral AD users, of which 4808 had a diagnosis of depression. The overall incidence rate of depression was 9.47/1000 person-years (PYs) (10.72/1000 PYs for women and 8.27/1000 PYs for men). The incidence of depression was higher during the year after oral AD treatment initiation. Independent factors associated with depression included having had mental disorders other than depression, hospitalization, a higher number of different drugs taken and of physicians visited during the year before oral AD initiation. Moreover, we observed a statistically significant age-by-socioeconomic status interaction.The incidence of diagnosed depression is higher during the first year after oral AD treatment initiation. Clinicians could pay particular attention to women, patients starting an AD at a young age, those with a low socioeconomic status, and especially those with a history of anxiety or dementia.

Visual and automated assessment of matrix metalloproteinase-14 tissue expression for the evaluation of ovarian cancer prognosis.

The purpose of this study was to evaluate whether the membrane type 1 matrix metalloproteinase-14 (or MT1-MMP) tissue expression, as assessed visually on digital slides and by digital image analysis, could predict outcomes in women with ovarian carcinoma. Tissue microarrays from a cohort of 211 ovarian carcinoma women who underwent a debulking surgery between 1993 and 2006 at the CHU de Québec (Canada) were immunostained for matrix metalloproteinase-14. The percentage of MMP-14 staining was assessed visually and with the Calopix software. Progression was evaluated using the CA-125 and/or the RECIST criteria according to the GCIG criteria. Dates of death were obtained by record linkage with the Québec mortality files. Adjusted hazard ratios of death and progression with their 95% confidence intervals were estimated using the Cox model. Comparisons between the two modalities of MMP-14 assessment were done using the box plots and the Kruskal-Wallis test. The highest levels of MMP-14 immunostaining were associated with nonserous histology, early FIGO stage, and low preoperative CA-125 levels (P<0.05). In bivariate analyses, the higher level of MMP-14 expression (>40% of MMP-14-positive cells) was inversely associated with progression using visual assessment (hazard ratio=0.39; 95% confidence interval: 0.18-0.82). A similar association was observed with the highest quartile of MMP-14-positive area assessed by digital image analysis (hazard ratio=0.48; 95% confidence interval: 0.28-0.82). After adjustment for standard prognostic factors, these associations were no longer significant in the ovarian carcinoma cohort. However, in women with serous carcinoma, the highest quartile of MMP-14-positive area was associated with progression (adjusted hazard ratio=0.48; 95% confidence interval: 0.24-0.99). There was no association with overall survival. The digital image analysis of MMP-14-positive area matched the visual assessment using three categories (>40% vs 21-40 vs <20%). Higher levels of MMP-14 immunostaining were associated with standard factors of better ovarian carcinoma prognosis. In women with serous carcinoma, high expression of MMP-14 was associated with lower progression.