Adherence to Guidelines at a Stroke Prevention Clinic: A Follow-up Study.

BACKGROUND: In 2010, we published our stroke prevention clinic's performance as compared to Canadian stroke prevention guidelines. We now compare our clinic's adherence with guidelines to our previous results, following the implementation of an electronic documentation form. METHODS: All new patients referred to our clinic (McGill University Health Center) for recent transient ischemic attack (TIA) or ischemic stroke between 2014 and 2017 were included. We compared adherence to guidelines to our previous report (N=408 patients for period 2008-2010) regarding vascular risk management and treatment. RESULTS: Three hundred and ninety-two patients were included, of which 36% had a TIA and 64% had an ischemic stroke, with a mean age of 70 years and 43% female. Although the more recent cohort has shown a higher proportion of cardioembolic stroke compared to previous (19.1% vs. 14.7%) following new guidelines regarding prolonged cardiac monitoring, increased popularity in CT angiography has not translated into greater proportion of large-artery stroke subtype (26.3% vs. 26.2%). Blood pressure (BP) targets were achieved in 83% compared with 70% in our previous report (p<0.01). Attainment of low-density lipoprotein cholesterol target was also improved in our recent study (66% vs. 46%, p<0.01). No significant difference was found in the consistency of antithrombotic use (97.7% vs. 99.8%, p=0.08). However, there was a decline in smoking cessation (35% vs. 73%, p=0.02). Overall, optimal therapy status was better attained in the present cohort compared to the previous one (52% vs. 22%, p<0.01). The male sex was associated with better attainment of optimal therapy status (odds ratio, 1.61; 95% confidence interval, 1.04-2.51). The number of follow-up visits and the length of follow-up were not associated with attainment of stroke prevention targets. CONCLUSIONS: Our study shows improvement in attainment of therapeutic goals as recommended by Canadian stroke prevention guidelines, possibly attributed in part to the implementation of electronic medical recording in our clinic. Areas for improvement include smoking cessation counseling and diabetes screening.

CONTEXTE: En 2010, nous avons rendu publics les résultats de notre clinique de prévention des AVC en ce qui regarde les lignes directrices canadiennes de prévention des AVC. Suite à la mise en place d'un formulaire d'information électronique, nous voulons maintenant comparer l'adhésion actuelle de notre clinique à ces lignes directrices à celle mesurée en 2010. MÉTHODES: Tous les nouveaux patients adressés à notre clinique (Centre universitaire de santé McGill) pour des cas récents d'ischémie cérébrale transitoire (ICT) ou d'AVC ischémique survenus entre 2014 et 2017 ont été inclus dans cette étude. Nous avons ainsi comparé l'adhésion actuelle aux lignes directrices évoquées ci-haut à celle du précédent rapport (N = 408 patients pour la période allant de 2008 à 2010), et ce, en ce qui concerne la prise en charge du risque vasculaire et les traitements nécessaires. RÉSULTATS: Au total, 392 patients ont été inclus; de ce nombre, 36 % d'entre eux avaient été victimes d'ICT tandis que 64 % avaient été victimes d'un AVC ischémique. Leur âge moyen était de 70 ans et 43 % d'entre eux étaient de sexe féminin. Bien que la cohorte la plus récente, à la suite de l'introduction de nouvelles lignes directrices portant sur la surveillance cardiaque prolongée, ait donné à voir une proportion plus élevée d'AVC d'origine cardio-embolique comparativement à la précédente (19,1 % par opposition à 14,7 %), la popularité croissante de l'angiographie par tomodensitométrie ne s'est pas traduite par une proportion plus grande de sous-types d'AVC affectant de grandes artères (26,3 % de 2014 à 2017 par opposition à 26,2 % de 2008 à 2010). Les valeurs cibles fixées en matière de pression artérielle ont été atteintes dans 83 % des cas comparativement à 70 % des cas dans notre rapport précédent (p < 0,01). L'atteinte de la valeur cible en ce qui concerne le taux de LDL-cholestérol (lipoprotéines de faible intensité) a également été améliorée dans notre plus récent rapport (66 % par opposition à 46 %; p < 0,01). Ajoutons aussi qu'aucune différence notable n'a été observée quant à une utilisation constante d'anti-thrombotiques (97,7 % par opposition à 99,8 %; p = 0,08). Fait à souligner, un déclin dans l'abandon du tabagisme a été noté (35 % par opposition à 73%; p = 0,02). Dans l'ensemble, les conditions d'une guérison optimale (optimal therapy status) ont été davantage atteintes dans la cohorte la plus récente comparativement à celle de 2008 à 2010 (52 % par opposition à 22 %; p < 0,01). Le fait d'être de sexe masculin a été associé à de meilleures conditions de guérison optimale (rapport des cotes: 1,61; IC 95 %, 1,04 ­ 2,51). Enfin, mentionnons que le nombre de consultations de suivi et la durée des suivis n'ont pas été associés à l'atteinte de valeurs cibles en matière de prévention des AVC. CONCLUSIONS: Notre étude montre une série d'améliorations dans l'atteinte des objectifs thérapeutiques recommandés par les lignes directrices canadiennes de prévention des AVC. Cela pourrait être en partie attribuable à la mise en place de dossiers médicaux informatisés au sein de notre clinique. Parmi les aspects qui méritent une amélioration, citons l'établissement d'un programme de counseling en ce qui regarde l'abandon du tabagisme et le dépistage du diabète.

An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides.

BACKGROUND: Receptors specific for the sugar N-acetylgalactosamine (GalNAc) include the human type II, C-type lectin receptor macrophage galactose-type lectin/C-type lectin receptor family member 10A (MGL/CLEC10A/CD301) that is expressed prominently by human peripheral immature dendritic cells, dendritic cells in the skin, alternatively-activated (M2a) macrophages, and to lesser extents by several other types of tissues. CLEC10A is an endocytic receptor on antigen-presenting cells and has been proposed to play an important role in maturation of dendritic cells and initiation of an immune response. In this study, we asked whether a peptide that binds in the GalNAc-binding site of CLEC10A would serve as an effective tool to activate an immune response against ovarian cancer. METHODS: A 12-mer sequence emerged from a screen of a phage display library with a GalNAc-specific lectin. The peptide, designated svL4, and a shorter peptide consisting of the C-terminal 6 amino acids, designated sv6D, were synthesized as tetravalent structures based on a tri-lysine core. In silico and in vitro binding assays were developed to evaluate binding of the peptides to GalNAc-specific receptors. Endotoxin-negative peptide solutions were administered by subcutaneous injection and biological activity of the peptides was determined by secretion of cytokines and the response of peritoneal immune cells in mice. Anti-cancer activity was studied in a murine model of ovarian cancer. RESULTS: The peptides bound to recombinant human CLEC10A with high avidity, with half-maximal binding in the low nanomolar range. Binding to the receptor was Ca2+-dependent. Subcutaneous injection of low doses of peptides into mice on alternate days resulted in several-fold expansion of populations of mature immune cells within the peritoneal cavity. Peptide sv6D effectively suppressed development of ascites in a murine ovarian cancer model as a monotherapy and in combination with the chemotherapeutic drug paclitaxel or the immunotherapeutic antibody against the receptor PD-1. Toxicity, including antigenicity and release of cytotoxic levels of cytokines, was not observed. CONCLUSION: sv6D is a functional ligand for CLEC10A and induces maturation of immune cells in the peritoneal cavity. The peptide caused a highly significant extension of survival of mice with implanted ovarian cancer cells with a favorable toxicity and non-antigenic profile.

Canadian stroke best practice recommendations: Secondary prevention of stroke, sixth edition practice guidelines, update 2017.

The 2017 update of The Canadian Stroke Best Practice Recommendations for the Secondary Prevention of Stroke is a collection of current evidence-based recommendations intended for use by clinicians across a wide range of settings. The goal is to provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations include those related to diagnostic testing, diet and lifestyle, smoking, hypertension, hyperlipidemia, diabetes, antiplatelet and anticoagulant therapies, carotid artery disease, atrial fibrillation, and other cardiac conditions. Notable changes in this sixth edition include the development of core elements for delivering secondary stroke prevention services, the addition of a section on cervical artery dissection, new recommendations regarding the management of patent foramen ovale, and the removal of the recommendations on management of sleep apnea. The Canadian Stroke Best Practice Recommendations include a range of supporting materials such as implementation resources to facilitate the adoption of evidence to practice, and related performance measures to enable monitoring of uptake and effectiveness of the recommendations. The guidelines further emphasize the need for a systems approach to stroke care, involving an interprofessional team, with access to specialists regardless of patient location, and the need to overcome geographic barriers to ensure equity in access within a universal health care system.

Relationship between adherence level to statins, clinical issues and health-care costs in real-life clinical setting.

OBJECTIVE: Statins have been shown to reduce the risk of major cardiovascular disease. We recognize that there is a major gap between the use of statins in actual practice and treatment guidelines for dyslipidemia. Low adherence to statins may have a significant impact on clinical issues and health-care costs. The objective is to evaluate the impact of low adherence to statins on clinical issues and direct health-care costs. METHODS: A cohort of 55,134 patients newly treated with statins was reconstructed from the Régie de l'Assurance Maladie du Québec and Med-Echo databases. Subjects included were aged between 45 and 85, initially free of cardiovascular disease, newly treated with statins between 1999 and 2002, and followed-up for a minimum of 3 years. Adherence to statins was measured in terms of the proportion of days' supply of medication dispensed over a defined period, and categorized as >or=80% or <80%. The adjusted odds ratio (OR) of cardiovascular events between the two adherence groups was estimated using a polytomous logistic analysis. The mean costs of direct health-care services were evaluated. A two-part model was applied for hospitalization costs. RESULTS: The mean high adherence level to statins was around to 96% during follow-up; and this value was at 42% for the low adherence level. The patients with low adherence to statins were more likely to have coronary artery disease (OR 1.07; 95% confidence interval [CI], 1.01-1.13), cerebrovascular disease (OR 1.13; 95% CI 1.03-1.25), and chronic heart failure within 3-year period of follow-up (OR 1.13; 95% CI 1.01-1.26). Low adherence to statins was also associated with an increased risk of hospitalization by 4% (OR 1.04; 95% CI 1.01-1.09). Among patients who were hospitalized, low adherence to statins was significantly associated with increase of hospitalization costs by approximately $1060/patient for a 3-year period. CONCLUSION: Low adherence to statins was correlated with a higher risk of cardiovascular disease, hospitalization rate, and hospitalization costs. An increased level of adherence to statins agents should provide a better health status for individuals and a net economic gain.

Stroke outcome in those over 80: a multicenter cohort study across Canada.

BACKGROUND AND PURPOSE: The prevalence of stroke in elderly patients has been increasing in recent years. However, limited information is available about the burden of stroke in individuals over 80. We sought to evaluate differences in clinical outcomes in Canadians over 80 years old hospitalized for an acute ischemic stroke. METHODS: The authors conducted a multicenter cohort study including all hospital admissions for ischemic stroke identified from the Canadian Hospital Morbidity and Mortality Database from April 2003 to March 2004. The Hospital Morbidity and Mortality Database contains a national database that contains patient-level sociodemographic, diagnostic, procedural, and administrative information from across Canada. Multivariable analysis was performed using logistic regression. The primary outcome was 7-day case fatality and fatality at discharge. Secondary end points included intensive care unit admissions, medical complications, gender differences, length of hospital stay, and discharge disposition. RESULTS: We analyzed 26,676 patients with ischemic stroke admitted to 606 hospitals across Canada. Mean age (SD) was 74+/-13 years. Overall, 10,171 (38%) were aged 80 years or older. Case fatality at discharge was 5.7% (age < 59), 8.6% (age 60 to 69), 13.4% (age 70 to 79), and 24.2% (age > or = 80; P<0.001). Patients aged 80 and over were less likely to be admitted to the intensive care unit (7.7% versus 15.3%; P<0.001) and discharged to their prestroke residence (47.2% for those over 80 versus 61.6% for patients younger than 80; P<0.001). Median length of stay was longer in those over 80 (10 days versus 7 days; P<0.0001). In the multivariable analysis for the older group, admission to the intensive care unit, low socioeconomic status, and admission to a nonacademic institution were associated with increased fatality after adjusting for covariates. CONCLUSIONS: Aging of the population is a growing reality in Western societies and this translates into an increasing demand on healthcare systems. In our study, patients with stroke over 80 had higher risk-adjusted fatality, longer hospitalization, and were less likely to be discharged to their original place of residence. Strategies need to be implemented to facilitate equal access to specialized stroke care for the elderly.

Efficacy and safety of pyridoxal 5'-phosphate (MC-1) in high-risk patients undergoing coronary artery bypass graft surgery: the MEND-CABG II randomized clinical trial.

CONTEXT: Coronary artery bypass graft (CABG) surgery is frequently performed and effective; however, perioperative complications related to ischemia-reperfusion injury, including myocardial infarction (MI), remain common and result in significant morbidity and mortality. MC-1, a naturally occurring pyridoxine metabolite and purinergic receptor antagonist, prevents cellular calcium overload and may reduce ischemia-reperfusion injury. Phase 2 trial data suggest that MC-1 may reduce death or MI in high-risk patients undergoing CABG surgery. OBJECTIVE: To assess the efficacy and safety of MC-1 administered immediately before and for 30 days after surgery in patients undergoing CABG surgery. DESIGN, SETTING, AND PARTICIPANTS: The MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery II Trial, a phase 3, multicenter, randomized, double-blind, placebo-controlled trial, with 3023 intermediate- to high-risk patients undergoing CABG surgery with cardiopulmonary bypass enrolled between October 2006 and September 2007 at 130 sites in Canada, the United States, and Germany. INTERVENTIONS: Patients received either MC-1, 250 mg/d (n = 1519), or matching placebo (n = 1504) immediately before and for 30 days after CABG surgery. MAIN OUTCOME MEASURES: The primary efficacy outcome was cardiovascular death or nonfatal MI, defined as a creatine kinase (CK) MB fraction of at least 100 ng/mL or new Q waves through postoperative day 30. RESULTS: The primary efficacy outcome occurred in 140 of 1510 patients (9.3%) in the MC-1 group and 133 of 1486 patients (9.0%) in the placebo group (risk ratio, 1.04; 95% confidence interval, 0.83-1.30; P = .76). All-cause mortality was higher among patients assigned to MC-1 than placebo at 4 days (1.0% vs 0.3%; P = .03) but was similar at 30 days (1.9% vs 1.5%; P = .44). There was no difference in the 8- to 24-hour CK-MB area under the curve between the MC-1 and placebo groups (median, 270 [interquartile range, 175-492] vs 268 [interquartile range, 170-456] hours x ng/mL; P = .11). CONCLUSION: In this population of intermediate- to high-risk patients undergoing CABG surgery, MC-1 did not reduce the composite of cardiovascular death or nonfatal MI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00402506

Effects of pyridoxal-5'-phosphate (MC-1) in patients undergoing high-risk coronary artery bypass surgery: results of the MEND-CABG randomized study.

OBJECTIVE: Coronary artery bypass graft surgery remains associated with significant postoperative cardiovascular morbidity and mortality in high-risk patients. MC-1 (pyridoxal-5'-phosphate monohydrate) inhibits purinergic receptors and intracellular influx of Ca2+, thereby reducing cellular injury during experimental ischemia and reperfusion. The MEND-CABG trial tested the hypothesis that MC-1 reduces cardiovascular morbidity and mortality after coronary artery bypass graft. METHODS: In a phase 2, double-blinded, placebo-controlled study, 901 patients scheduled for coronary artery bypass graft surgery with cardiopulmonary bypass and at high risk for subsequent cardiac or neurologic complications were randomly assigned to receive oral MC-1 (250 mg or 750 mg/d once daily) or placebo beginning 3 to 10 hours prior to surgery and continued to postoperative day 30. RESULTS: At 30 days, MC-1 250 mg (compared with placebo) reduced the composite of death, nonfatal cerebral infarction, and nonfatal myocardial infarction by 14.0% (P = .3124) with peak creatinine kinase-myocardial band > or =50 ng/mL (prespecified primary end point); 32.3% (P = .0349) with peak creatinine kinase-myocardial band > or =70 ng/mL; and 37.2% (P = .0283) with peak creatinine kinase-myocardial band > or =100 ng/mL. Myocardial infarctions with peak creatinine kinase-myocardial band> or =100 ng/mL were reduced by 47.2% in the MC-1 250-mg group versus placebo (P = .0083). Greater efficacy was demonstrated with 250 mg than with the 750-mg dose of MC-1. CONCLUSIONS: In high-risk patients undergoing coronary artery bypass graft, treatment with MC-1 did not significantly affect the prespecified primary end point but was associated with a significant reduction in perioperative myocardial infarction with creatinine kinase-myocardial band > or =100 ng/mL. A larger, well-powered trial is needed to evaluate the cardioprotective effects of MC-1.

Meeting the nutritional needs of patients with severe dysphagia following a stroke: an interdisciplinary approach.

Dysphagia is a common problem with individuals who have experienced a stroke. The interdisciplinary stroke team noted delays in clinical decision-making, or in implementing plans for patients with severe dysphagia requiring an alternative method to oral feeding, such as enteral feeding via Dobhoff (naso-jejunum) or PEG (percutaneous endoscopic gastrostomy) tubes, occurred because protocols had not been established. This resulted in undernourishment, which in turn contributed to clinical problems, such as infections and confusion, which delayed rehabilitation and contributed to excess disability. The goal of the project was to improve quality of care and quality of life for stroke patients experiencing swallowing problems by creating a dysphagia management decision-making process. The project began with a retrospective chart review of 91 cases over a period of six months to describe the population characteristics, dysphagia frequency, stroke and dysphagia severity, and delays encountered with decision-making regarding dysphagia management. A literature search was conducted, and experts in the field were consulted to provide current knowledge prior to beginning the project. Using descriptive statistics, dysphagia was present in 44% of the stroke population and 69% had mild to moderate stroke severity deficit. Delays were found in the decision to insert a PEG (mean 10 days) and the time between decision and PEG insertion (mean 12 days). Critical periods were examined in order to speed up the process of decision-making and intervention. This resulted in the creation of a decision-making algorithm based on stroke and dysphagia severity that will be tested during winter 2002.