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.

A systematic review of caregiver burden following stroke.

Abstract Caregiver burden following stroke is increasingly recognised as a significant health care concern. A growing number of studies have evaluated the patient, caregiver, and social support factors that contribute to increased caregiver burden. We conducted a systematic review of this literature to guide future research. A search of the MEDLINE, PsycINFO, CINAHL, and EMBASE databases (up to July 2008) and reference sections of published studies using a structured search strategy yielded 24 relevant articles. Studies were included if they evaluated predictors and/or correlates of caregiver burden in the setting of stroke. The prevalence of caregiver burden was 25-54% and remained elevated for an indefinite period following stroke. In studies that evaluated independent baseline predictors of subsequent caregiver burden, none of the factors reported were consistent across studies. In studies that assessed concurrent factors independently contributing to caregiver burden in the poststroke period, patient characteristics and social support factors were inconsistently reported. Several studies identified caregiver mental health and the amount of time and effort required of the caregiver as significant determinants of caregiver burden. Our findings highlight the need for more research to identify caregivers in need of support and guide the development and implementation of appropriate interventions to offset caregiver burden.

Caring for stroke survivors: baseline and 1-year determinants of caregiver burden.

BACKGROUND: Caregiver burden following stroke can have significant adverse health consequences for caregivers and threatens the recovery and successful rehabilitation of patients. Our objective was to identify patient factors that contribute to higher levels of caregiver burden. METHODS: We prospectively studied patients admitted to our stroke unit over a 2-year period (2001-2002). Data were collected at baseline and at 1 year. Caregiver burden was measured at 1 year using the Relatives Stress Scale (completed by 155 caregivers) and the Bakas Caregiver Outcomes Scale (143 caregivers). Explanatory patient factors at baseline included sociodemographic status, stroke severity, stroke sub-type, functional disability (Barthel Index), functional handicap (Oxford Handicap Scale and Modified Rankin Scale), and cognitive status (orientation, clock drawing). At 1 year, mental health and health-related quality of life were assessed using the Fatigue Impact Scale, Geriatric Depression Scale, Global Deterioration Scale, and 36-item Short Form Health Survey. RESULTS: The baseline patient factors predictive of caregiver burden by multiple regression analysis were older patient age (P<0.01), male gender (P<0.05), ischemic stroke (P<0.05), urinary incontinence (P<0.0001), and impaired clock drawing (P<0.05). At 1 year, significant correlates of caregiver burden were older patient age (P<0.05), male gender (P<0.01), poor mental health (P<0.05), functional handicap (P<0.05), and functional disability (P<0.001). CONCLUSIONS: The functional status of patients can be used to identify caregivers at risk of caregiver burden. Patient demographic variables, cognitive function, and mental health status may further expose vulnerable caregivers. These factors should be considered in the development of strategies to offset caregiver burden.

Enzymatic hydrolysis of PTT polymers and oligomers.

Oligomers and polymers (film, fabrics) of the linear aromatic polyester poly(trimethylene terephthalate) (PTT) were treated with polyesterases from Thermomyces lanuginosus, Penicillium citrinum, Thermobifida fusca and Fusarium solani pisi. The cutinase from T. fusca was found to release the highest amounts of hydrolysis products from PTT materials and was able to open and hydrolyse a cyclic PTT dimer according to RP-HPLC-UV detection. In contrast, the lipase from T. lanuginosus also showed activity on the PTT fibres and on bis(3-hydroxypropyl) terephthalate (BHPT) but was not able to hydrolyse the polymer film, mono(3-hydroxypropyl) terephthalate (MHPT) nor the cyclic dimer of PTT. As control enzymes inhibited with mercury chloride were used. Surface hydrophilicity changes were investigated with contact angle measurements and the degree of crystallinity changes were determined with DSC.

A case-control study of tissue plasminogen activator for acute ischemic stroke.

BACKGROUND: Randomized trials demonstrate that intravenous tissue plasminogen activator (tPA) improves outcome in acute ischemic stroke (AIS). To assess translation of this efficacy into effectiveness in routine clinical practice we performed a case-control study of tPA treatment for AIS in a single hospital. METHODS: 151 tPA-treated AIS patients (1996-2005) were matched 1:1 with blinding to outcome to controls from a prospective registry based on age, gender, pre-stroke Oxford handicap scale (OHS), stroke severity, and subtype. The outcomes were in-hospital death, symptomatic intracranial hemorrhage (SICH), length-of-stay (LOS), discharge OHS and long-term survival. RESULTS: In-hospital mortality (23% vs. 24%) or long-term survival (median follow-up of 2 years) was not different between cases and controls (p = 0.83). SICH occurred in 7.8% (95% CI 4.2-13.5%) of tPA-treated patients. Median LOS was non-significantly shorter for cases (13 [7-29] vs. 16 [8-32] days, p = 0.14) but significantly shorter in tPA-treated vs. non-treated women (14 [7-28] vs. 20 [11-34] days, p = 0.04). At discharge 6.6% (95% CI 1.1-12.0%) more tPA-treated patients than controls had no disability (OHS < or = 1, p = 0.02). However, there was no difference in discharge independence rates or proportion discharged home. CONCLUSION: We demonstrate minor improvements in early recovery after stroke with tPA but the impact is less dramatic than that reported in randomized trials. This may relate to timing of treatment and the type of patients treated.

External validation of a six simple variable model of stroke outcome and verification in hyper-acute stroke.

We aimed to validate a previously described six simple variable (SSV) model that was developed from acute and sub-acute stroke patients in our population that included hyper-acute stroke patients. A Stroke Outcome Study enrolled patients from 2001 to 2002. Functional status was assessed at 6 months using the modified Rankin Scale (mRS). SSV model performance was tested in our cohort. 538 acute ischaemic (87%) and haemorrhagic stroke patients were enrolled, 51% of whom presented to hospital within 6 h of symptom recognition. At 6 months post-stroke, 42% of patients had a good outcome (mRS < or = 2). Stroke patients presenting within 6 h of symptom recognition were significantly older with higher stroke severity. In our Stroke Outcome Study dataset, the SSV model had an area under the curve of 0.792 for 6 month outcomes and performed well for hyper-acute or post-acute stroke, age < or > or = 75 years, haemorrhagic or ischaemic stroke, men or women, moderate and severe stroke, but poorly for mild stroke. This study confirms the external validity of the SSV model in our hospital stroke population. This model can therefore be utilised for stratification in acute and hyper-acute stroke trials.

Sonochemical substrate selectivity and reaction pathway of systematically substituted azo compounds.

The sonochemical degradation of the systematically substituted azo compound 2,7-dihydroxy-1-phenylazonaphthaline-3,6-disulfonic acid was investigated using a frequency of 850 kHz and an acoustic input power of 61 W. All derivatives were degraded completely within 6h by the ultrasonic treatment. Trifluoromethyl substituted azo compounds exhibited 2-3-fold higher degradation rates in comparison to the reference hydrogen substituted azo compound (k=0.54 h(-1)). In contrast to enzymatic processes (azoreductase or laccase), the ultrasonic treatment for these ortho-, meta-, and para-substituted azo compound showed 1.5-50-fold higher degradation rates. Additionally the ultrasound treatment was characterized by shorter reaction times. As a result of the detection and identification of specific intermediates using LC-MS a reaction pathway of the sonochemical degradation of the analysed azo compound is proposed indicating the formation of cyclohexadienone and naphthalene quinone derivatives.

Restricting detergent protease action to surface of protein fibres by chemical modification.

Due to their excellent properties, such as thermostability, activity over a broad range of pH and efficient stain removal, proteases from Bacillus sp. are commonly used in the textile industry including industrial processes and laundry and represent one of the most important groups of enzymes. However, due to the action of proteases, severe damage on natural protein fibres such as silk and wool result after washing with detergents containing proteases. To include the benefits of proteases in a wool fibre friendly detergent formulation, the soluble polymer polyethylene glycol (PEG) was covalently attached to a protease from Bacillus licheniformis. In contrast to activation of PEG with cyanuric chloride (50%) activation with 1,1'-carbonyldiimidazole (CDI) lead to activity recovery above 90%. With these modified enzymes, hydrolytic attack on wool fibres could be successfully prevented up to 95% compared to the native enzymes. Colour difference (DeltaE) measured in the three dimensional colour space showed good stain removal properties for the modified enzymes. Furthermore, half-life of the modified enzymes in buffers and commercial detergents solutions was nearly twice as high as those of the non-modified enzymes with values of up to 63 min. Out of the different modified proteases especially the B. licheniformis protease with the 2.0-kDa polymer attached both retained stain removal properties and did not hydrolyse/damage wool fibres.

Influence of redox mediators and metal ions on synthetic acid dye decolourization by crude laccase from Trametes hirsuta.

In this paper, the effect of redox mediators on synthetic acid dye decolourization (Sella Solid Red and Luganil Green) by laccase from Trametes hirsuta cultures has been investigated. All the redox mediators tested, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 1-hydroxybenzotriazole (HBT) and Remazol Brilliant Blue R (RBBR), led to higher activities than those obtained without mediators addition showing the suitability of the laccase/mediator system (LMS) in the decolourization of acid dyes. HBT was by far the most effective mediator, showing a decolourization percentage of 88% in 10 min for Sella Solid Red and of 49% in 20 min for Luganil Green. On the other hand, the stability of laccase against several metal ions, normally found in textile wastewater, was assessed. Laccase was stable at a concentration of 1mM for 7d against all the metal ions tested except for Zn+2, CrO4(-2), Cd+2, Cr2O7(-2), Fe+2, Cu+2 and especially Hg+2. When the concentration was increased to 10mM laccase stability decreased against all the metals assayed, in particular against Fe+2. In addition, the effect of metal ions on the decolourization process was also studied. It was found that Hg+2 inhibited the dye decolourization process, being the presence of HBT absolutely required for dye decolourization.

Anticoagulants for acute ischaemic stroke.

BACKGROUND: Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulant therapy could have a significant impact on patient survival, disability and stroke recurrence. OBJECTIVES: The objective of this review was to assess the effect of anticoagulant therapy versus control in the early treatment of patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched 30 October 2003). For previous updates of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies. SELECTION CRITERIA: Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Twenty-two trials involving 23,547 patients were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on nine trials (22,570 patients) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio (OR) = 1.05, 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up. Similarly, based on six trials (21,966 patients), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow-up (OR = 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was associated with about 9 fewer recurrent ischaemic strokes per 1000 patients treated (OR = 0.76; 95% CI 0.65 to 0.88), it was also associated with a similar sized 9 per 1000 increase in symptomatic intracranial haemorrhages (OR = 2.52; 95% CI 1.92 to 3.30). Similarly, anticoagulants avoided about 4 pulmonary emboli per 1000 (OR = 0.60, 95% CI 0.44 to 0.81), but this benefit was offset by an extra 9 major extracranial haemorrhages per 1000 (OR = 2.99; 95% CI 2.24 to 3.99). Sensitivity analyses did not identify a particular type of anticoagulant regimen or patient characteristic associated with net benefit. REVIEWERS' CONCLUSIONS: Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke. People treated with anticoagulants had less chance of developing deep vein thrombosis (DVT) and pulmonary embolism (PE) following their stroke, but these sorts of blood clots are not very common, and may be prevented in other ways.

Stainless steel sponge: a novel carrier for the immobilisation of the white-rot fungus Trametes hirsuta for decolourization of textile dyes.

Alginate beads, polyurethane foam, nylon sponge and stainless steel sponge were tested as carrier materials for the white-rot fungus Trametes hirsuta for laccase production under submerged fermentation conditions. Stainless steel sponge was the best carrier material leading to the highest laccase activities of up to 800 U/l after 8 days of cultivation. These values are higher than those reported to date operating with inert supports and without inducer addition. In a 1-l bioreactor containing T. hirsuta immobilised on stainless steel sponge laccase activities of about 2200 U/l were obtained when the culture medium was supplemented with 1 mM copper sulphate. There were no operational problems with this system during culturing time. The textile dye Indigo Carmine was almost totally degraded in 3 days by T. hirsuta grown in this bioreactor, while Lanaset Marine was degraded in two successive batches, reaching in the first batch a decolourization percentage of about 82% in 15 h and in the second one by 71% in 28 h. Results obtained after inhibition of growth of T. hirsuta by antibiotics indicated that dye decolourization could not exclusively be attributed to laccase activity.

Antiplatelet therapy for acute ischaemic stroke.

BACKGROUND: In patients with acute ischaemic stroke, platelets become activated. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and reduce the risk of early recurrent ischaemic stroke. This might reduce the risk of early death and improve long-term outcome in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage. OBJECTIVES: The aim of this review is to assess the efficacy and safety of antiplatelet therapy in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched August 2002), the Cochrane Controlled Trials Register (CCTR) (Cochrane Library Issue 1 2002), MEDLINE (June 1998-October 2001), and EMBASE (June 1998-February 2002). In 1998, for previous versions of this review, we searched the register of the Antiplatelet Trialists Collaboration, MedStrategy and contacted relevant drug companies. SELECTION CRITERIA: Randomised trials comparing antiplatelet therapy (started within 14 days of the stroke) with control in patients with definite or presumed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria and assessed trial quality, and for the included trials, extracted and cross-checked the data. MAIN RESULTS: Nine trials involving 41,399 patients were included. Two trials testing aspirin 160 to 300 mg once daily started within 48 hours of onset contributed 98% of the data. The maximum follow-up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow-up (OR = 0.94; 95% CI 0.91 to 0.98). In absolute terms, 13 more patients were alive and independent at the end of follow-up for every 1000 patients treated. Furthermore, treatment increased the odds of making a complete recovery from the stroke (OR = 1.06; 95% CI 1.01 to 1.11). In absolute terms, 10 more patients made a complete recovery for every 1000 patients treated. Antiplatelet therapy was associated with a small but definite excess of 2 symptomatic intracranial haemorrhages for every 1000 patients treated, but this was more than offset by a reduction of 7 recurrent ischaemic strokes and about one pulmonary embolus for every 1000 patients treated. REVIEWER'S CONCLUSIONS: Antiplatelet therapy with aspirin 160 to 300 mg daily, given orally (or per rectum in patients who cannot swallow), and started within 48 hours of onset of presumed ischaemic stroke reduces the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications and improves long-term outcome.

An immobilised catalase peroxidase from the alkalothermophilic Bacillus SF for the treatment of textile-bleaching effluents.

A catalase peroxidase (CP) from the newly isolated Bacillus SF was used to treat textile-bleaching effluents. The enzyme was stable at high pH values and temperatures, but was more sensitive to deactivation by hydrogen peroxide than monofunctional catalases. Based on the Michaelis-Menten kinetics of the CP, a model was developed to describe its deactivation characteristics. The enzyme was immobilised on various alumina-based carrier materials with different shapes and the specific activity increased with the porosity of the carrier. The shape of the carrier had an important influence on the release of oxygen formed during the catalase reaction from the packed-bed reactor and Novalox saddles were found to be the most suitable shape. Bleaching effluent was treated in a horizontal packed-bed reactor containing 10 kg of the immobilised CP at a textile-finishing company. The treated liquid (500 l) was reused within the company for dyeing fabrics with various dyes, resulting in acceptable colour differences of below Delta E*=1.0 for all dyes.

Production of laccase by a newly isolated strain of Trametes modesta.

The effects of the carbon and nitrogen sources, initial pH and incubation temperature on laccase production by Trametes modesta were evaluated using the one-factor-at-a-time method. The final optimisation was done using a central composite design resulting in a four-fold increase of the laccase activity to 178 nkat ml(-1). Response-surface analysis showed that 7.34 g l(-1) wheat bran, 0.87 g l(-1) glucose, 2.9 g l(-1) yeast extract, 0.25 g l(-1) ammonium chloride, an initial pH of 6.95 and an incubation temperature of 30.26 degrees C were the optimal conditions for laccase production. Laccase produced by T. modesta was fully active at pH 4 and at 50 degrees C. The laccase was very stable at pH 4.5 and at 40 degrees C but half-lives decreased to 120 and 125 min at higher temperature (60 degrees C) and lower pH (pH 3).

Decolorization of textile dyes by laccases from a newly isolated strain of Trametes modesta.

Four ligninolytic fungi, Trametes modesta, Trametes hirsuta, Trametes versicolor and Sclerotium rolfsii, were compared for their ability to produce laccases. The fungal laccases were screened for their ability to decolorize eight synthetic dyes (anthraquinone, azo, indigo and triarylmethane). The decolorization rate depended both on the source of the enzyme preparation and on the structure of the dye. Based on laccase production and dye decolorizing ability, T. modesta was selected for further studies. All the tested dyes were decolorized by the T. modesta laccase most efficiently under acid conditions (pH 3-6) but the optimum pH for decolorization of the individual dye varied. The decolorization rate of this laccase increased with the rise in temperature to 50-60 degrees C. The decolorization efficiency of T. modesta laccase was improved remarkably in the presence of mediators like 1-hydroxybenzotriazole and 2-methoxyphenothiazine.

Chiral separation of beta-methyl-amino acids by ligand exchange using capillary electrophoresis and HPLC.

This paper deals with the chiral separation of optical isomers of beta-methyl-amino acids by CE and HPLC using the principle of ligand-exchange. Capillary zone electrophoresis was carried out using Cu(II) complexes of L-4-hydroxyproline (L-4-Hypro), N-(2-hydroxypropyl)-L-4-hydroxyproline (HP-L-4-Hypro) and N-(2-hydroxyoctyl)-L-4-hydroxyproline (HO-L-4-Hypro) as chiral selectors, added to the electrolyte. The HPLC separations were performed on a chiral stationary ligand-exchange chromatography phase containing L-4-Hypro chemically bonded to silica gel. With both techniques nearly all compounds investigated are baseline resolved using different background electrolytes and mobile phases, respectively.

Chiral separation of pharmacologically active dihydropyrimidinones with carboxymethyl-beta-cyclodextrin.

We report on the chiral separation of pharmacologically active dihydropyrimidinones by capillary electrophoresis (CE) using carboxymethyl-beta-cyclodextrin as chiral selector. The influence of selector concentration, pH, and the addition of varying amounts of methanol is investigated. Out of 21 compounds investigated, 19 were resolved, 13 with baseline separation.

Characterization of a chitinase and an endo-beta-1,3-glucanase from Trichoderma harzianum Rifai T24 involved in control of the phytopathogen Sclerotium rolfsii.

Of 24 Trichoderma isolates, T harzianum Rifai (T24) showed a potential for control of the phytopathogenic basidiomycete Sclerotium rolfsii. When T24 was grown on different carbon sources, growth inhibition of S. rolfsii by the T24 culture filtrate correlated with the activity of extracellular chitinase and beta-1,3-glucanase. The 43-kilodalton (kDa) chitinase and the 74-kDa beta-1,3-glucanase were purified from the T24 culture filtrate in two and three steps, respectively, using ammonium sulphate precipitation followed by hydrophobic interaction chromatography (phenyl-Sepharose) and gel filtration (beta-1,3-glucanase). Km and Kcat were 3.8 g l(-1) and 0.71 s(-1) for the chitinase (chitin) and 1.1 g(-1) and 52 s(-1) for the beta-1,3-glucanase (laminarin). The chitinase showed higher activity on chitin than on less-acetylated substrate analogues (chitosan), while the beta-1,3-glucanase was specific for beta-1,3-linkages in polysaccharides. Both enzymes were stable at 30 degrees C, while at 60 degrees C the chitinase and the beta-1,3-glucanase were rapidly inactivated, showing half-lives of 15 and 20 min, respectively. The enzymes inhibited growth of S. rolfsii in an additive manner showing a promising ED50 (50% effective dose) value of 2.7 microg/ml.