Canadian Stroke Best Practice Recommendations for Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care, 6th Edition, Update 2018.

The 2018 update of the Canadian Stroke Best Practice Recommendations for Acute Stroke Management, 6th edition, is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners caring for persons with very recent symptoms of acute stroke or transient ischemic attack. The recommendations are intended for use by a interdisciplinary team of clinicians across a wide range of settings and highlight key elements involved in prehospital and Emergency Department care, acute treatments for ischemic stroke, and acute inpatient care. The most notable changes included in this 6th edition are the renaming of the module and its integration of the formerly separate modules on prehospital and emergency care and acute inpatient stroke care. The new module, Acute Stroke Management: Prehospital, Emergency Department, and Acute Inpatient Stroke Care is now a single, comprehensive module addressing the most important aspects of acute stroke care delivery. Other notable changes include the removal of two sections related to the emergency management of intracerebral hemorrhage and subarachnoid hemorrhage. These topics are covered in a new, dedicated module, to be released later this year. The most significant recommendation updates are for neuroimaging; the extension of the time window for endovascular thrombectomy treatment out to 24 h; considerations for treating a highly selected group of people with stroke of unknown time of onset; and recommendations for dual antiplatelet therapy for a limited duration after acute minor ischemic stroke and transient ischemic attack. This module also emphasizes the need for increased public and healthcare provider's recognition of the signs of stroke and immediate actions to take; the important expanding role of paramedics and all emergency medical services personnel; arriving at a stroke-enabled Emergency Department without delay; and launching local healthcare institution code stroke protocols. Revisions have also been made to the recommendations for the triage and assessment of risk of recurrent stroke after transient ischemic attack/minor stroke and suggested urgency levels for investigations and initiation of management strategies. The goal of this updated guideline is to optimize stroke care across Canada, by reducing practice variations and reducing the gap between current knowledge and clinical practice.

Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile.

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

The epidemiological and economic effects from systematic depopulation of Norwegian marine salmon farms infected with pancreas disease virus.

Pancreas disease (PD) is a viral disease associated with significant economic losses in Scottish, Irish, and Norwegian marine salmon aquaculture. In this paper, we investigate how disease-triggered harvest strategies (systematic depopulation of infected marine salmon farms) towards PD can affect disease dynamics and salmon producer profits in an endemic area in the southwestern part of Norway. Four different types of disease-triggered harvest strategies were evaluated over a four-year period (2011-2014), each scenario with different disease-screening procedures, timing for initiating the harvest interventions on infected cohorts, and levels of farmer compliance to the strategy. Our approach applies a spatio-temporal stochastic model for simulating the spread of PD in the separate scenarios. Results from these simulations were then used in cost-benefit analyses to estimate the net benefits of different harvest strategies over time. We find that the most aggressive strategy, in which infected farms are harvested without delay, was most efficient in terms of reducing infection pressure in the area and providing economic benefits for the studied group of salmon producers. On the other hand, lower farm compliance leads to higher infection pressure and less economic benefits. Model results further highlight trade-offs in strategies between those that primarily benefit individual producers and those that have collective benefits, suggesting a need for institutional mechanisms that address these potential tensions.

The economic benefits of disease triggered early harvest: A case study of pancreas disease in farmed Atlantic salmon from Norway.

Pancreas disease (PD) is an important viral disease in Norwegian, Scottish and Irish aquaculture causing biological losses in terms of reduced growth, mortality, increased feed conversion ratio, and carcass downgrading. We developed a bio-economic model to investigate the economic benefits of a disease triggered early harvesting strategy to control PD losses. In this strategy, the salmon farm adopts a PCR (Polymerase Chain Reaction) diagnostic screening program to monitor the virus levels in stocks. Virus levels are used to forecast a clinical outbreak of pancreas disease, which then initiates a prescheduled harvest of the stock to avoid disease losses. The model is based on data inputs from national statistics, literature, company data, and an expert panel, and use stochastic simulations to account for the variation and/or uncertainty associated with disease effects and selected production expenditures. With the model, we compared the impacts of a salmon farm undergoing prescheduled harvest versus the salmon farm going through a PD outbreak. We also estimated the direct costs of a PD outbreak as the sum of biological losses, treatment costs, prevention costs, and other additional costs, less the costs of insurance pay-outs. Simulation results suggests that the economic benefit from a prescheduled harvest is positive once the average salmon weight at the farm has reached 3.2kg or more for an average Norwegian salmon farm stocked with 1,000,000smolts and using average salmon sales prices for 2013. The direct costs from a PD outbreak occurring nine months (average salmon weight 1.91kg) after sea transfer and using 2013 sales prices was on average estimated at NOK 55.4 million (5%, 50% and 90% percentile: 38.0, 55.8 and 72.4) (NOK=€0.128 in 2013). Sensitivity analyses revealed that the losses from a PD outbreak are sensitive to feed- and salmon sales prices, and that high 2013 sales prices contributed to substantial losses associated with a PD outbreak.

Controlling emerging infectious diseases in salmon aquaculture.

In this paper, the authors review the impacts of diseases facing salmon aquaculture, drawing lessons from terrestrial animal diseases. They discuss the implementation of current control strategies, taking into account transmission patterns (vertical versus horizontal), disease reservoirs, and interactions with wild fish. In addition, the decision-making context of aquatic disease control and the institutional organisation of control strategies are considered, with particular emphasis on the roles and responsibilities of regulatory authorities and the private sector. Case studies on the emergence and control of infectious salmon anaemia worldwide and pancreas disease in Norway are used to examine some of the controversies that may influence decision making and provide lessons for the future.

Long-term outcome of resective epilepsy surgery in Norwegian children.

AIM: The aim of this study was to evaluate the long-term results of resective surgery on children with difficult-to-treat epilepsy in Norway. METHODS: In the period 1995-2004, 64 surgical procedures (54 resections and 10 functional hemispherotomies) were performed in 54 children. The children's medical records were retrospectively reviewed at a minimum of 2 years after surgery. We sent a questionnaire regarding their epilepsy (seizures, usage of antiepileptic drugs) and general functioning (social situation, motor, language, cognition, behavioural or emotional problems, any remedial action) to the children/parents after a mean follow-up period of 7 years. RESULTS: 55.5% of the children were seizure-free. The success rate varied according to the type of surgery. Best results were found after functional hemispherotomies and temporal lobe resections, as nine of 10 (90%) and 10 of 19 (53%) of these patients, respectively, became seizure-free. In addition to a better seizure control, 71% of the children/parents reported of a better cognitive and psychosocial functioning. CONCLUSION: The results of epilepsy surgery in this paediatric cohort are very edifying, and it is our impression that this treatment option is underused in Norway.

Good long-term efficacy of pallidal stimulation in cervical dystonia: a prospective, observer-blinded study.

BACKGROUND AND PURPOSE: Deep brain stimulation of the internal globus pallidus (GPi-DBS) is established as an effective treatment of primary generalised dystonia in controlled studies. In cervical dystonia (CD), only one previous study has reported observer-blinded outcome assessment of long-term GPi-DBS, with 1-year follow-up. METHODS: In this prospective, single-centre study, eight patients with CD (7 women:1 man, 4 focal:4 segmental) treated with bilateral GPi-DBS for median (range) 30 (12-48) months, were evaluated by the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS; Severity, Disability and Pain scores), the Short-Form Health Survey-36 (SF-36), and the Becks Depression Index in an open design. In addition, a blinded rater assessed the TWSTRS Severity score from videos obtained preoperatively and at the last follow-up. RESULTS: In the blinded evaluation, median (range) TWSTRS Severity score improved from 25 (19-30) to 8 (4-23) (P = 0.028), thus a 70% (23-82) score reduction. In the open evaluation, median Severity score improvement at the last follow-up was 73%, representing a significant further improvement from 50% at 6 months. The Disability and Pain scores improved by median 91% and 92%, respectively, and the SF-36 subdomain scores improved significantly. A reversible right hemiparesis and aphasia occured in one patient 4 days postoperatively, because of reversible oedema around the left electrode. No other serious adverse effects and no permanent morbidity were observed. CONCLUSIONS: This single-blinded study shows good long-term efficacy of GPi-DBS in CD patients and supports using this treatment in those who have insufficient response to medical treatment.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment.

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

CT perfusion quantification of small-vessel ischemic severity.

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) abnormalities are previously demonstrated in white matter disease. A gradation of change may exist between patients with mild and more severe white matter disease. An association between blood brain barrier dysfunction, increasing age and white matter disease is also suggested. The purpose of this study was to quantify and correlate white matter disease severity and CT perfusion (CTP)-derived CBF and to determine whether permeability surface abnormality increases with white matter disease severity. MATERIALS AND METHODS: One hundred twenty patients with strokelike symptoms underwent CTP and MR imaging. Of these, 35 patients (15 women, 20 men; age, 66 +/- 15.7 years) with rapidly resolving symptoms and normal imaging characteristics consistent with transient ischemic attack were retrospectively reviewed and constituted the study cohort. Two blinded neurologists rated white matter severity, assigning age-related white matter change (ARWMC) scores. Patients were dichotomized a priori into mild and moderate-to-severe. CBF, cerebral blood volume (CBV), mean transit time (MTT), and permeability surface product maps were calculated for periventricular and subcortical white matter regions and average white and gray matter. Associations with white matter severity were tested by uni- and multivariate logistic regression analyses. Receiver operating characteristic analysis was performed. RESULTS: White matter disease was mild in 26 patients and moderate-to-severe in 9. Age was associated with increased likelihood of having moderate-to-severe white matter disease (P = .02). ARWMC correlated with subcortical (r = -0.50, P < .001) and average CBF (r = -0.55, P < .001). White matter severity was associated with subcortical (P = .03) and average (P = .03) white matter CBF, with a trend toward periventricular white matter CBF (P = .05). Uni- and multivariate analysis controlling for the confounding effect of age demonstrated significant association between white matter severity and subcortical (P = .032) white matter CBF. Area under the curve was 0.82. No permeability surface abnormality was found. CONCLUSIONS: CTP-derived subcortical white matter CBF is independently associated with white matter disease severity.

Insular cortical ischaemia does not independently predict acute hypertension or hyperglycaemia within 3 h of onset.

OBJECTIVES: To test the hypothesis that insular cortical ischaemia is associated with acute hypertension and hyperglycaemia. METHODS: From the Canadian Activase for Stroke Effectiveness Study, which included only patients treated with thrombolysis hyperacutely (ie, within 3 h of onset of stroke), 966 patients were identified with ischaemia affecting (n = 685), or sparing (n = 281), the insular cortex. Demographic and clinical data, pretreatment indices of blood pressure, blood glucose, atrial fibrillation, and clinical imaging and outcome measures were compared between the two groups. Multivariable linear regression was used to assess predictors of systolic blood pressure and glucose levels before thrombolysis. RESULTS: Pretreatment hypertension (p = 0.009), but not hyperglycaemia (p = 0.32), was predicted by insular ischaemia in univariable linear regression analyses. After adjusting for other factors, however, insular cortical ischaemia was not found to be an independent predictor for acute hypertension or hyperglycaemia. CONCLUSIONS: Raised blood pressure or serum glucose levels in hyperacute (<3 h) cerebral ischaemia is not independently predicted by insular involvement. Several hours are required for sympathetic manifestations of insular ischaemia to evolve.

Intra-arterial thrombolysis for retinal artery occlusion: the Calgary experience.

INTRODUCTION: Retinal artery occlusion represents a medical emergency with poor prognosis for visual recovery. Spontaneous improvement is estimated to occur in less than 15% of central retinal artery occlusion (CRAO) cases and conventional treatments have provided only limited benefit. Intra-arterial thrombolysis has been reported as a potentially efficacious and safe treatment. METHODS: We performed a retrospective chart review of all retinal artery occlusion cases treated with intra-arterial recombinant tissue-type plasminogen activator (rtPA) from January 1998 to May 2004. Patients received Goldmann perimetry visual field testing at a variable interval following the procedure (2 days-2.5 years). Visual acuity (VA) was re-assessed in May 2004. RESULTS: Eight cases (59-77 years) were treated for CRAO, 6-18 hours post-onset with intra-arterial rtPA (10-20 mg over 15-60 minutes); one case of branch occlusion (BRAO) was treated with 30 mg rtPA over 75 minutes, 12 hours post-onset. Among the six patients with CRAO assessed in clinic, three experienced improvement in VA by two or more gradations (Snellen lines); three improved by one gradation. However, none achieved a final VA better than 20/300. The case of branch occlusion improved to a VA of 20/20. All patients had residual monocular field defects. CONCLUSIONS: Our findings reveal a limited benefit for intra-arterial tPA compared to the rate of spontaneous improvement and conventional forms of therapy for retinal artery occlusion.

Does rugby headgear prevent concussion? Attitudes of Canadian players and coaches.

OBJECTIVES: To examine the attitudes of players and coaches to the use of protective headgear, particularly with respect to the prevention of concussion. METHODS: A questionnaire designed to assess attitudes to headgear was administered to 63 players from four different Canadian teams, each representing a different level of play (high school, university, community club, national). In addition, coaches from all four levels were questioned about team policies and their personal opinions about the use of headgear to prevent concussion. RESULTS: Although the players tended to believe that the headgear could prevent concussion (62%), the coaches were less convinced (33%). Despite the players' belief that headgear offers protection against concussion, only a minority reported wearing headgear (27%) and few (24%) felt that its use should be made mandatory. Common reasons for not wearing headgear were "its use is not mandatory", "it is uncomfortable", and "it costs too much". CONCLUSION: Although most players in the study believe that rugby headgear may prevent concussion, only a minority reported wearing it. Coaches tended to be less convinced than the players that rugby headgear can prevent concussion.

Preclinical pharmacology of CP-424,391, an orally active pyrazolinone-piperidine [correction of pyrazolidinone-piperidine] growth hormone secretagogue.

Growth hormone secretagogues (GHSs) represent attractive therapeutic alternatives to recombinant growth hormone (GH), given their ability to amplify pulsatile hormone secretion in a relatively physiologic manner. CP-424,391 (391) is a novel, orally active pyrazolinone-piperidine [corrected] GHS. In rat pituitary cell cultures, 391 stimulated GH release with an EC50 = 3 nM. The addition of 391 to rat pituitary cells activated intracellular calcium signaling but did not elevate intracellular cyclic adenosine monophosphate (cAMP). 391 also modulated the effects of GH-releasing hormone and somatostatin on pituitary cell GH-release and intracellular signaling. In nonpituitary cell lines, the ability of 391 to stimulate intracellular signaling was dependent on the expression of recombinant human GHS receptor. Acute administration of 391 to anesthetized rats or to conscious dogs induced pulsatile release of G H in a dose-dependent manner. Plasma insulin-like growth factor-I (IGF-I) was elevated progressively over a 5-d course of daily oral dosing in dogs. Chronic oral administration of 391 augmented body weight gain in rats and dogs. Thus, the peptidomimetic GHS 391 has potential utility for the treatment of clinical conditions that could benefit from systemic augmentation of GH and IGF-I levels.

Effect of Norwegian fish powder on risk factors for coronary heart disease among hypercholesterolemic individuals.

BACKGROUND AND AIM: Numerous studies suggest an association between high intake of fatty fish and reduced risk of coronary heart disease. Very long-chain omega-3 fatty acids are thought to be responsible for the benefits observed, though other fatty fish components may act in concert with them. Norwegian fish powder is a dry herring product that contains essential amino acids, marine omega-3 fatty acids, vitamins and minerals. The aim of the present study was to determine whether it has beneficial effects on risk factors for coronary heart disease in man. METHODS AND RESULTS: A single center, randomized, double-blind, parallel-treatment study was carried out for 12 weeks. Subjects with primary hypercholesterolemia were randomly allocated to 10 g fish powder or placebo (20 tablets/day). Participants were instructed to follow National Cholesterol Education Program (NCEP) Step I Diet during a 4-week diet run-in phase and during the study. Concentrations of lipids, lipoproteins, hemostatic variables and endothelial cell markers were determined before and after supplementation. Our data showed that the fish powder supplement was well tolerated. A significant decrease and increase respectively were observed in plasma alpha-linolenic acid (p = 0.03) and docosahexaenoic acid (DHA) (p = 0.03). Concentrations of lipids, lipoproteins, homocysteine, factor VII, fibrinogen, tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI)-1, soluble intercellular adhesion molecule (ICAM)-1, P-selectin and interleukin (IL)-8 were not beneficially affected. CONCLUSIONS: Fish powder supplementation does not seem an effective approach to improve risk factors for coronary heart disease in hypercholesterolemic subjects following the NCEP Step I Diet.

Colloidal blood volume expansion during high intracranial pressure.

This study tested the hypothesis that colloidal blood volume expansion could improve the cerebral circulation during high intracranial pressure. We studied cerebrovascular haemodynamic variables during high intracranial pressure with and without colloidal blood volume expansion in 12 pigs, whereas five pigs served as controls with intracranial pressure increase twice without colloidal blood volume expansion. Cerebral blood flow was measured with ultrasonic flowmetry on the internal carotid artery, and cerebral microcirculation with laser Doppler flowmetry. High intracranial pressure was induced by infusion of artificial cerebrospinal fluid into the cisterna magna. Blood volume expansion was obtained by infusion of albumin, 1 gram/kg. Albumin infusion caused increases in internal carotid artery blood flow (P < 0.05) and cerebral perfusion pressure (P < 0.005), while cerebral microcirculation and cerebrovascular resistance was unchanged. High intracranial pressure albumin infusion caused internal carotid artery blood flow (P < 0.05) and cerebral perfusion pressure (P < 0.001) to increase compared to high intracranial pressure without albumin infusion, while cerebrovascular resistance was unchanged. Cerebral micro-circulation tended to increase, but this was not statistically significant (P = 0.07). Augmentation of the intravascular blood volume during high intracranial pressure increased the arterial inflow to the brain and possibly the cerebral microcirculation by increasing the cerebral perfusion pressure. Our results tend to support that the effect of colloidal blood volume expansion is beneficial for the cerebral circulation during high intracranial pressure.

A 2-year comparison study of Crl:CD BR and Hsd:Sprague-Dawley SD rats.

In this 2-year study, the suitability of the Hsd:Sprague-Dawley SD (SD) as a replacement for the Crl:CD BR (CD) rat was assessed by comparing survival rates, palpable mass incidence, body weights, food consumption, clinical laboratory parameters, and necropsy and histopathology observations. At week 104, survival rates in the CD and SD males were 29 and 49%, respectively. Corresponding survival rates in females were 44 and 63%. The total numbers of animals with palpable masses and animals with neoplasms were similar in the CD and SD rats; however, the total numbers of palpable masses and neoplasms were higher in the CD rats. The incidence of corneal lesions was higher in the SD rats, whereas the incidence of lenticular opacities was higher in the CD rats. Body weights, food and water consumption, and organ weights were significantly lower in the SD rats. In contrast, food intake per kilogram of body weight was slightly higher in the SD rats. Numerous differences in clinical laboratory parameters between the CD and SD rats were observed. Some of these were consistent with the increased prevalence of kidney disease and secondary sequelae in the SD rats. Taken together, the better survival, smaller size, and lower food consumption of the SD rat may make it a better model for chronic bioassays. However, the increased propensity for spontaneous renal disease may limit the utility of the SD rat for studying nephrotoxic compounds.

Minor vascular anatomy of the abdomen and pelvis: a CT atlas.

With the early generations of computed tomographic (CT) scanners, interpretation of abdominal and pelvic scans focused on the solid organs, hollow viscera, and retroperitoneum. Attention to blood vessels generally was given only to the aorta and inferior vena cava and their larger branches. The newer generations of scanners allow rapid acquisition of high-resolution images during the vascular phase of mechanical bolus injection of intravenous contrast material. Visualization of second-order vascular branches has thus become routine. Recent improvements in software allow real-time reconstruction of data in multiple planes, which enables demonstration of long segments of vessels within a single image. Approximately 7,000 abdominal and pelvic CT scans were reviewed with attention to vascular detail. Cases are presented that illustrate peripancreatic, perigastric, parietal, and hypogastric vessels; fetal remnants and structures that may be mistaken for vessels; and collateral pathways of both arterial and venous flow. With increasing use of helical CT scanning, smaller vessels can be identified with greater confidence. Knowledge of normal CT vascular anatomy facilitates understanding of collateral pathways when vessel engorgement is perceived.

[Splenic neoplasms]. / Neoplasmer i milt.

Carcinomas of the spleen are rare, whether primary or secondary. Two patients are described, one with a primary angiosarcoma. In this patient the first symptom was abdominal pain, caused by spontaneous rupture of the spleen. The other case was a woman with carcinoma of the breast which metastasized to the spleen. Both underwent splenectomy and adjuvant oncological treatment. Angiosarcomas constitute less than 1% of all sarcomas. Only about 60 cases of angiosarcomas in the spleen have been reported in the world literature. Spontaneous rupture of the spleen occurred in 30% of these cases. The prognosis for both untreated and treated splenic angiosarcomas is poor. Virtually all malignant tumours have been shown to metastasize to the spleen, most frequently from primary tumours localised to the breast, lung or ovary. Neoplasm should be considered for patients with splenomegaly having no apparent cause.