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Introduction: Postoperative delirium (POD) is an important complication of major surgery in elderly patients. It increases morbidity and mortality, hospital stay, and total healthcare costs. Since no treatment has proven effective once POD is established, prevention is key. Evidence exists that bispectral index guided anesthesia (BIS-GA) and antipsychotics may independently reduce incidence of POD, but the efficacy of combining these preventive strategies is unknown. Objective: To compare the combination of olanzapine + BIS-GA with BIS-GA alone for prevention of POD in elderly patients undergoing major elective surgery.Methods: We propose a Phase II, multi-center, randomized, double-blind, parallel, placebo-controlled trial. The study arms will be BIS-GA + two doses of olanzapine 5mg given pre and postoperatively compared with BIS-GA + placebo in patients ≥65 years hospitalized for major elective surgery. Exclusion criteria include cardiac- and neurosurgery, dementia history, concurrent antipsychotic, anticholinergic, or sedative-hypnotic use, olanzapine allergy, delirium at hospital admission, cognitive impairment and inability to be interviewed. The primary outcome is incidence of POD diagnosed by DSM-V criteria and assessed by the Confusion Assessment Method (CAM) scale. Secondary outcomes include delirium severity, rescue therapy use, length of hospital stay and incidence of adverse events.Discussion: There is an increasing need for trials that advance knowledge in prophylactic methods to prevent delirium. By combining two preventive methods, we expect to decrease the incidence of POD, which will result in decreased morbidity, mortality, and total healthcare costs.

Background Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. In Brazil, even though low-molecular-weight heparin (LMWH) is the gold standard of care for the management of cancer-associated thrombosis (CAT), its cost limits its use and therefore warfarin is commonly prescribed. Direct oral anticoagulants (DOACs), such as edoxaban, have been introduced as an alternative in this setting. Objective The aim of this study was to compare the cost-effectiveness of edoxaban with LMWH (Model 1) and warfarin (Model 2) to support clinicians and hospitals when choosing an anticoagulant to manage CAT. Materials and methods Cost-effectiveness analyses were performed using Markov state-transition models over a timeframe of 5 years, in a hypothetical, 64 years-old patients cancer population with an index VTE event. Transition probabilities, costs, quality-adjusted life years (QALYs) and risk reductions were either derived from the literature, estimated or calculated. A willingness-to-pay limit of 3 Gross Domestic Product (GDP) per head was used. Deterministic and probabilistic sensitivity analyses were performed for robustness. The main outcome of this study was the incremental cost-effectiveness ratio (ICER), expressed as cost per QALY gained. Results Model 1 base case analysis demonstrated dominance of edoxaban compared to LMWH, with an ICER of $5204.46, representing cost saved per QALY lost. In Model 2, edoxaban was associated with a $736.90 cost increase vs. warfarin, with an ICER of $2541.03. Sensitivity analyses confirmed base-case results. Conclusion Edoxaban represents a cost-saving alternative to LMWH for the management of CAT and is cost-effective vs. warfarin.

Introduction: Primary dysmenorrhea affects many women, being a major cause of absenteeism and reduced productivity at work and at school. Although non-steroidal anti-inflammatory drugs (NSAIDs) are a good treatment option, up to 18% of women show no response or present allergic reactions and adverse events. Curcumin has antispasmodic, antinociceptive, and both specific and nonspecific anti-inflammatory effects, with good tolerability and safety. To date, no previous trial involving curcumin and dysmenorrhea pain has been performed. Therefore, our main goal is to assess the efficacy of curcumin for pain relief among women with primary dysmenorrhea, along with determining curcumin’s adverse effects and tolerability profile.Methods: A phase II, single-center, randomized, triple-blinded, placebo-controlled, parallel-group, superiority trial to evaluate the effect of curcumin (500 mg/12h) in pain reduction in women (18 to 35-year-old) with primary dysmenorrhea. A first cycle will be used for a passive, observational run-in phase. A sample of 108 participants (54 per group) is necessary to detect a 30% difference in pain sensitivity between groups assessed by visual analogue scale (VAS). Secondary outcomes include side effects, Cox Menstrual Symptom Scale (CMSS), and use of rescue drugs for pain relief. Discussion: Clinical evidence has shown analgesic and anti-inflammatory effects of curcumin and in view of dysmenorrhea’s physiopathology being related to those mechanisms targeted by curcumin, we hypothesize its use could represent an innovative and effective therapy to reduce the severity of this disease and its symptoms. Keywords: primary dysmenorrhea, Curcumin, pain relief, Visual Analogue Scale, Cox Menstrual Symptom Scale.

Background: We characterized clinical and imaging phenotypes and their association with clinical outcomes in acute ischemic stroke (AIS) survivors in the understudied region of Costa Rica. Methods: We conducted a retrospective cohort study in AIS patients treated at a tertiary stroke center in Costa Rica from 2011–2015. Participants underwent detailed phenotyping for cardiovascular risk factors and stroke etiology. We assessed the association of ischemic brain lesion features and clinical outcomes using the Oxfordshire Community Stroke Project (OCSP) classification. Results: We included 684 AIS survivors (60.2% males, aged 68.1 ± 13.6 years, mean ± SD). While the cardiovascular risk profiles and mortality rates of our patients were similar to populations in European and North American countries, only 20.2% of patients with atrial fibrillation (AF) received anticoagulation. On multivariable analysis, patients with total anterior circulation infarct (TACI) displayed an increased risk of complications (OR: 4.2; 95% CI: 2.2–7.8; p < 0.001), higher mortality (OR: 6.9; 95% CI: 2.9–16.1; p < 0.001) and lower chance of functional independence at discharge (OR: 8.9; 95% CI: 4.1–19; p < 0.001) compared to non-TACI. The comorbidity of bronchopneumonia increased the probability of death by 14.5 times. Conclusions: Our observations in a Costa Rican cohort of AIS survivors might help improve local measures for preventing and managing AIS.

Objetivo: determinar el desarrollo cognitivo de lactantes de madres expuestas y no expuestas al humo del tabaco durante la gestación. Métodos: estudio transversal analítico, muestreo no probabilístico por cuotas; durante el periodo de marzo a mayo de 2020 participaron 236 binomios (madre-hijo) adscritos a una unidad de primer nivel de atención; se aplicó el test de desarrollo cognitivo Denver ii. Los criterios de inclusión fueron lactantes con esquema de vacunación completo, peso y tamiz neonatal normal, madres de entre quince y 45 años con antecedente de embarazo normo-evolutivo, binomios que refirieron exposición y no exposición al humo del tabaco de manera activa o pasiva durante la gestación. Se realizó estadística descriptiva para variables sociodemográficas, se relacionó la variable exposición al humo de tabaco con la variable desarrollo cognitivo mediante el coeficiente de correlación Spearman y se determinó fuerza de asociación mediante el modelo de regresión lineal.Resultados: la asociación del desarrollo cognitivo con la exposición al humo de tabaco reportó una correlación de Spearman de 0.227 (pConclusiones: existe una relación estadísticamente no significativa entre el desarrollo cognitivo de lactantes con la exposición al humo de tabaco durante la gestación.

By 2030, the United Nations projects a population growth of almost 1 billion people in the world. Independent of its economic power, all countries will face great challenges. The scarcity of natural resources, the tendency to urban concentration, the climate change and the lack of opportunities, among other factors, will lead societies to a more dynamic competition. In such a complex future, education becomes a fundamental element for the development of the skills that today's children and youth need to face the future of work.

El presente documento busca profundizar en los elementos que componen la economía popular partiendo de las razones sociales que llevan a las personas a tomar este tipo de iniciativas sociales. El acercamiento teórico es una ampliación de la investigación sobre economía popular solidaria como una propuesta eficaz para promover el desarrollo social y superar la pobreza. Para ello se realiza un análisis crítico de la literatura y se profundiza en los aspectos significativos que contribuyen a la construcción de la teoría objeto de estudio. La metodología empleada en esta fase de la investigación es el análisis documental determinando las causas que conllevan a la generación de este tipo de decisiones económicas sociales. Con el documento se concreta un acercamiento conceptual de economía popular y sus diferentes representaciones facilitando el entendimiento de este fenómeno como parte de un proceso de democratización del mercado y como una respuesta a la exclusión, identificando autores y conceptos inherentes a ella. La revisión y el análisis permiten conjeturar que la Economía Popular puede representar un medio para superar la pobreza y mejorar el desarrollo social en las comunidades caracterizadas por altos niveles de desocupación e inequidad socioeconómica

Temporal lobe epilepsy (TLE) is a common form of epilepsy that presents with complex partial seizures and in some cases with generalization to tonic-clonic activity that are often well controlled with antiepileptic medication in up to two thirds of patients. The remaining one third with “medically i

Objetivo: evaluar la asociación entre el apoyo social funcional y la percepción de la relación con sus padres en adolescentes fumadores y no fumadores. Métodos: estudio transversal analítico realizado en la Unidad de Medicina Familiar (umf) no. 64 del Instituto Mexicano del Seguro Social (imss) de marzo a mayo de 2018; participaron 250 adolescentes de trece a diecisiete años de edad, contestaron la escala argentina de percepción de la relación con los padres y el cuestionario de apoyo social funcional Duke-unc. Se realizó estadística descriptiva, cálculo de frecuencias y relación de variables mediante χ2. Resultados: la relación entre apoyo social funcional y ser o no fumador reportó una χ2 de 0.733 con una p=0.392; la asociación percepción de la relación con el padre o la madre con ser o no fumador registró una χ2 de 2.147 y 3.129 respectivamente, con un valor de p>0.05 para ambos casos. Conclusiones: no existe una relación estadísticamente significativa entre el apoyo social funcional y la percepción de la relación con sus padres con el tabaquismo en los adolescentes evaluados.

Objetivo: evaluar la asociación entre el apoyo social funcional y la percepción de la relación con sus padres en adolescentes fumadores y no fumadores. Métodos: estudio transversal analítico realizado en la Unidad de Medicina Familiar (umf) no. 64 del Instituto Mexicano del Seguro Social (imss) de marzo a mayo de 2018; participaron 250 adolescentes de trece a diecisiete años de edad, contestaron la escala argentina de percepción de la relación con los padres y el cuestionario de apoyo social funcional Duke-unc. Se realizó estadística descriptiva, cálculo de frecuencias y relación de variables mediante χ2. Resultados: la relación entre apoyo social funcional y ser o no fumador reportó una χ2de 0.733 con una p=0.392; la asociación percepción de la relación con el padre o la madre con ser o no fumador registró una χ2 de 2.147 y 3.129 respectivamente, con un valor de p>0.05 para ambos casos. Conclusiones: no existe una relación estadísticamente significativa entre el apoyo social funcional y la percepción de la relación con sus padres con el tabaquismo en los adolescentes evaluados.

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.

Le risque d'accident vasculaire cerebral (AVC) chez les patients porteurs d'une stenose carotidienne asymptomatique (SCA) est maintenant si faible qu'il est important d'etablir des criteres pour identifier les patients qui sont les plus susceptibles de beneficier d'une intervention ou chez qui on doit porter une attention particuliere au choix du traitement medical. Nous avons examine si la presence d'une stenose arterielle intracrânienne et de microembolies au Doppler transcrânien (DTC) etaient des facteurs de prediction de l'AVC, du deces ou d'acces ischemiques transitoires (AIT) (AVC/deces/AIT) chez des patients porteurs d'une SCA ainsi que l'effet du diabete sur les microembolies, la stenose intracrânienne et le risque d'evenements. Methode: Nous avons recrute des patients presentant une SCA > 60% a l'echographie Doppler a la clinique de prevention de l'AVC a l'hopital universitaire de London, en Ontario, au Canada. Les 339 participants ont subi un DTC pour la detection de la stenose intracrânienne et de microembolies et une echographie carotidienne pour mesurer la stenose extracrânienne et la surface totale de plaque. Les participants ont ete suivis pendant 3 ans afin de determiner le risque d'AVC/deces/AIT. Resultats: Un AVC/deces/AIT est survenu chez 38% des patients avec microembolies et chez 10% de ceux qui n'en avaient pas (p = 0,0001) ainsi que chez 18% des patients porteurs d'une stenose intracrânienne et chez 10% de ceux qui n'en avaient pas (p = 0,042). Les diabetiques etaient significativement plus susceptibles de presenter une stenose intracrânienne que ceux qui n'etaient pas diabetiques (45% par opposition a 29%; p = 0,014), des microembolies (38% par opposition a 10%; p < 0,0001) et ils avaient un risque significativement plus eleve d'AVC/deces/AIT au cours des trois annees d'observation (21% par opposition a 11%; p = 0,024). La survie sans AVC, AIT ou deces etait significativement meilleure sans microembolies ou stenose intracrânienne (p < 0,0001). Conclusions: Le diabete, les microembolies et la stenose intracrânienne predisaient un risque plus eleve d'AVC, de deces ou d'AIT que la stenose extracrânienne ou la surface totale de plaque. Il se peut que les diabetiques aient besoin d'un traitement plus energique.

Objective: We compared microemboli on transcranial Doppler (TCD) with carotid ulcerations on 3D ultrasound (US) as an additional method for identifying the small proportion of patients with asymptomatic carotid stenosis (ACS) who can benefit from revascularization such as endarterectomy or stenting. Methods: Patients with ACS (n = 253) with carotid stenosis >60% by Doppler ultrasound were studied prospectively with TCD embolus detection and 3D US to detect ulcers (the total number of ulcers in both internal carotids) and followed for 3 years. Results: Mean age was 69.66 (SD 8.51) years; 11 (4%) had ≥3 ulcers (Ulcer 3), 11 (6%) had microemboli, and 25 (10%) had microemboli or ≥3 ulcers. Ulcer 3 patients were more likely to have a stroke or death in 3 years (18% vs 2%; p = 0.03), regardless of the side on which the ulcers were found. The 3-year risk of stroke or death was 20% with microemboli vs 2% without ( p = 0.003). The annual rate of ipsilateral stroke was 0.8%. Conclusion: Adding 3D US detection of ulcers doubles (to 10%) the proportion of patients with ACS who may benefit from endarterectomy or stenting. However, until 3-year event rates of stroke or death with endarterectomy or stenting reach Neurology ® 2011;77:744–750

This study investigated the use of population-based administrative databases for stroke surveillance. First, a meta-analysis was conducted of four studies, identified via a PubMed search, which estimated the sensitivity and specificity of hospital data for ascertaining cases of stroke when clinical registries or medical charts were the gold standard. Subsequently, case-ascertainment algorithms based on hospital, physician and prescription drug records were developed and applied to Manitoba's administrative data, and prevalence estimates were obtained for fiscal years 1995/96 to 2003/04 by age group, sex, region of residence and income quintile. The meta-analysis results revealed some over-ascertainment of stroke cases from hospital data when the algorithm was based on diagnosis codes for any type of cerebrovascular disease (Mantel-Haenszel Odds-Ratio [OR] – 1.70 [95% confidence interval (CI): 1.53 – 1.88]). Analyses of Manitoba administrative data revealed that while the total number of stroke cases varied substantially across the algorithms, the trend in prevalence was stable regardless of the algorithm adopted.

Dans la présente étude, nous nous sommes penchés sur l'utilisation des bases de données administratives en matière de population dans la surveillance des accidents vasculaires cérébraux. Nous avons tout d'abord effectué une méta-analyse de quatre études, relevées au moyen d'une recherche dans PubMed, qui visaient à évaluer la sensibilité et la spécifi cité des données des hôpitaux dans la détermination des cas d'accident vasculaire cérébral lorsque les registres cliniques ou les dossiers médicaux étaient la méthode de référence. Nous avons ensuite mis au point des algorithmes de détermination des cas fondés sur les données des hôpitaux ainsi que les données relatives aux médecins et aux médicaments de prescription. Enfin, nous avons appliqué ces algorithmes aux données administratives du Manitoba, ce qui a permis d'obtenir des estimations de la prévalence pour les années fi nancières 1995-1996 à 2003-2004, par groupe d'âge, sexe, région de résidence et quintile de revenu. Les résultats de la méta-analyse ont fait ressortir une certaine surdétermination des cas d'accident vasculaire cérébral à partir des données des hôpitaux, lorsque l'algorithme était fondé sur les codes de diagnostic applicables à n'importe quel type de maladie vasculaire cérébrale (rapport de cotes de Mantel-Haenszel [RC] = 1,70 [intervalle de confiance (IC) à 95 % : 1,53-1,88]). Les analyses des données administratives du Manitoba ont révélé que même si le nombre total de cas d'accident vasculaire cérébral variait considérable ment selon l'algorithme, la tendance de la prévalence était stable indépendamment de l'algorithme utilisé.

The complexity of human diet resides in the heterogeneity of sources (e.g., animals, grains, vegetables, and fruits), preservatives used, and cultural, religious, and geographic factors. Other factors include age, personal preferences, concomitant diseases, and even genetic predispositions (e.g., gluten sensitivity). Growing evidence has shown that multiple dietary substrates increase the risk of stroke by increasing blood pressure or adversely contributing to atherogenesis.1 Excess salt intake, low potassium intake, excess weight, and high alcohol consumption increase the risk of hypertension.2 The American Heart Association (AHA)1,2 and the Canadian Stroke Best Practices recommend a sodium intake of less than 1,500 mg/d (avoiding processed foods), a diet high in fresh fruits, vegetables, low-fat dairy products, dietary and soluble fiber, whole grains, and very low alcohol consumption.3

Background Among patients with a patent foramen ovale and cryptogenic ischemic stroke, the long-term prognosis is unclear. Aims This study aims to estimate the recurrence rate in young cryptogenic stroke patients with and without patent foramen ovale. Patients and methods One hundred eighty-six cryptogenic stroke patients (aged 18–45 years) were prospectively followed for up to five-years. They were divided into two groups according to the echocardiographic presence of patent foramen ovale. All patients received aspirin (100mg/day) for secondary prevention. Results Mean age was 32·3 (standard deviation 7·9) years. During the mean follow-up of 66 months five patients with patent foramen ovale had recurrent strokes compared with 11 patients without patent foramen ovale. The average annual rate of recurrent cerebral ischemia was 1·1% and 1·6% for patients with and without patent foramen ovale, respectively. The recurrence rate did not increase with the presence of patent foramen ovale, atrial septal aneurysm or other variables. More than 60% of the reported cases achieved a good functional outcome. Conclusions Young patients with cryptogenic ischemic stroke with and without patent foramen ovale have a low recurrence rate in a long-term follow-up and most present a favorable outcome. Patent foramen ovale with or without atrial septal aneurysm did not increase the risk of recurrence.

Background Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~ 25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism. Methods Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO. Results Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23–15.69; p = 0.023), prolonged travel (OR, 8.77; 95% CI, 1.775–43.3; p = 0.008) , migraine (OR, 2.30: 95% CI, 1.07–4.92; p = 0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15–9.64; p = 0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26–16.2; p = 0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9 ± 3 versus 7.9 ± 2.6 µmol/L respectively; p = 0.021). Conclusions A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.

Background and Purpose— Carotid endarterectomy clearly benefits patients with symptomatic severe stenosis (SCS), but the risk of stroke is so low for asymptomatic patients (ACS) that the number needed to treat is very high. We studied transcranial Doppler (TCD) embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat. Methods— Patients with carotid stenosis of ≥60% by Doppler ultrasound who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%) were studied with TCD embolus detection for up to 1 hour on 2 occasions a week apart; patients were followed for 2 years. Results— 319 patients were studied, age (standard deviation) 69.68 (9.12) years; 32 (10%) had microemboli at baseline (TCD+). Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4 versus 1.4%; P P Conclusions— Our findings indicate that TCD− ACS will not benefit from endarterectomy or stenting unless it can be done with a risk

Background and Purpose— New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. Methods— In 38 patients with carotid stenosis >60%, age±SD 69.42±7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. Results— There were no significant differences in baseline risk factors. The rate of progression was 16.81±74.10 mm 3 in patients taking placebo versus regression of −90.25±85.12 mm 3 in patients taking atorvastatin ( P Conclusions— 3D plaque volume measurement can show large effects of therapy on atherosclerosis in 3 months in sample sizes of ≈20 patients per group. Sample sizes of 22 per group would be sufficient to show an effect size of 25% that of atorvastatin in 6 months. This technology promises to be very useful in evaluation of new therapies.

Thrombolysis for acute stroke is beneficial in selected patients. Because clinical trials generally exclude patients with pre-existing disability, this subgroup of patients has not been studied. We examined the outcomes after thrombolysis of patients with and without disability before their stroke.We prospectively followed 112 consecutive patients with acute ischemic stroke who were given intravenous thrombolysis treatment according to published protocols. Three-month outcomes of the patients with pre-existing disability (defined as a prestroke score of 2 or more on the modified Rankin scale [MRS]) were compared with those of patients without pre-existing disability (defined as a prestroke MRS score of 0 or 1) and with those of 168 patients similarly treated in the National Institute of Neurological Disorders and Stroke trial.At 3 months after the stroke, patients with pre-existing disability (21% of the 112) had a higher mortality rate than those without (33% v. 14%) (odds ratio 3.2, 95% confidence interval 1.0-10.1) and worse function (median MRS score 3 v. 2, p = 0.03). However, there was little difference between the 2 groups in neurologic impairment among the survivors (median score on the National Institutes of Health stroke scale 4 v. 2, p = 0.41) or in the total proportion of those with an MRS score of 0 or 1 or, for those with a prestroke score greater than 1, a return to the prestroke score (42% v. 41%, p = 0.87).Although the true effectiveness of thrombolysis for acute stroke in patients with pre-existing disability is not known, treated patients appear able to return to their prestroke level of function as often as patients without pre-existing disability, despite a significantly higher mortality rate.

Background and Purpose — Guidelines for intravenous tissue plasminogen activator (tPA) use in stroke emphasize the importance of limiting its use to facilities with imaging capabilities and stroke expertise. This prospective case series set out to evaluate the safety of tPA use in patients referred from rural communities to a tertiary center. Methods — Prospective data of 82 consecutive patients treated with tPA in London, Ontario, were reviewed. Results — Twenty-three patients were transferred to London from a rural hospital (non-London patients); 49 were first evaluated in a London emergency room (London ER); and 10 were inpatients in a London hospital at the time of stroke onset. Mean transfer time and distance to London for non-London patients were 89 minutes and 41 miles. Although symptom onset to London ER times were longer for non-London than for London ER patients (123 versus 53 minutes), the door to needle times were significantly shorter for the former (49 versus 95 minutes, P P =0.16). The proportion of patients with >4-point improvement on the NIH Stroke Scale or cure at 24 hours was 57%, with no difference among groups ( P =0.46). The overall symptomatic hemorrhage rate at 36 hours was 2%. No significant differences in outcomes were observed at 3 months. Conclusions — This prospective study suggests that it is feasible and safe to treat rural patients referred to a tertiary care center with tPA, thus extending the benefits of thrombolysis for acute stroke to a wider population.

During the last two decades, evidence has shown an association between patent foramen ovale (PFO) and cryptogenic stroke, predominantly in younger patients. In a meta-analysis of case-control studies, approximately 35%–50% of patients with cryptogenic ischemic stroke had a PFO, vs only 4%–10% of age-matched patients. That is a fivefold increase risk of cryptogenic stroke in younger patients with PFO.1 However, causality and its recurrence seem to be more complex, considering that 27% of the general population has this vestige of fetal circulation.2 The risk of stroke recurrence due to the failure of the primum and secundum septa to fuse postnatally is low. In the PFO-ASA trial, the recurrence in aspirin-treated patients was 2.3% in 4 years vs 4.2% observed in those without an interatrial septal abnormality. This risk strikingly increased to 15.2% if coexisting atrial septal aneurysm (ASA) was present.3 The ASA-PFO embolic mechanism is unclear but it is possibly related to motion dynamics influencing flow through the PFO leading to paradoxical emboli or possibly being a nidus for thrombus formation. In other …

To the Editor: Emergency room (ER) physicians and neurologists are critical in ensuring a prompt evaluation of patients arriving at the ER within 3 hours of symptom onset and in initiating therapy with tPA. Suboptimal institutional readiness for evaluating patients with acute stroke and fear about the hemorrhagic complications among neurologists are some of the factors that can limit the widespread use of tPA, as reported by Katzan et al.1 Family physicians play an important role in educating patients at risk for stroke about the warning signs of stroke and the importance of contacting 911 as soon as these appear. Limited knowledge about the benefits and an unjustified fear of the side effects may limit stroke patients’ access to this treatment. …

P163 Background: Although, elderly patients (≥80 years) are not excluded from receiving tPA for acute ischemic stroke (AIS), uncertainty still exists regarding the effectiveness and safety of tPA in this age group. Objective: To compare baseline characteristics, outcomes, and complications of AIS patients treated with iv tPA aged ≥80 with their younger counterparts (Methods: Patients ≥80 were compared to the younger group aged 1/3 middle cerebral artery territory was involved. Findings: To date 62 patients have been treated. Median ages of the young group (n=46) are 68 years (range of 37–79) and of the older group (n=16) are 85 years (range of 80–93). Thirty-one of 46 younger patients and eleven of 16 older patients have reached the 3 month follow-up mark. The elderly group had a statistically significant higher mean pre-stroke Modified Rankin Score (mRS) of 1.5 compared to 0.6 for the younger group (p=0.01). The mean initial National Institutes of Health Stroke Scale Scores (NIHSSS), and mean time to tPA from stroke onset do not differ significantly: 14 (young) and 17 (old) (p=0.07), and 151 minutes (young) and 155 minutes (old) (p=0.67). Percent of patients achieving ≥4 point improvement in NIHSS 24 hours post tPA, a 3 month NIHSS of 0–1, and a 3 month MRS of 0–1 are 63 V.S. 44 (p=0.29), 35 V.S. 36 (p=0.80)and 41 V.S. 9 (p=0.12) for the young and old groups respectively. Only one patient (age 81) had a fatal intracranial hemorrhage (ICH). No other patients in the registry suffered a symptomatic ICH. Of the younger group, 11% and of the elderly group, 19% had an asymptomatic ICH (p=0.71). Conclusions: Despite the elderly patients having greater pre-stroke disability, iv tPA for AIS in this group does not significantly differ in effectiveness and complications compared to the same treatment in patients under age 80. TPA should not be withheld from AIS patients on the basis of age alone.

P196 Background: Many rural community hospitals (RCH) in Southwestern Ontario lack a CT scanner. The stroke team (ST) in London provides tertiary care to these RCH. Advance notification of transfer of non-London patients (NLP) from RCH allows the ST to manage them from arrival at the LER. In contrast, the ST is notified of London patients (LP) after their arrival and registration in the London ER (LER). Objective: Assess feasibility of tPA administration to rural patients transferred to a tertiary care center. Methods: Mean symptom to LER, door to imaging, imaging to tPA, and door to tPA (DtPA) for LP and NLP times were compared. In-patients were excluded from the analysis. Results: Between Dec 1, 98 and Jun 30, 00, 61 patients were treated with tPA in London: 16 (26%) were NLP, 45 (74%) were local (37 LP, 8 in-patients). For NLP the mean symptom to RCH time was 37 mins, the mean RCH to LER distance was 41 miles (range 11–80) and the mean transfer time was 90 mins. (range 46–138). Symptom onset to LER time was significantly longer for NLP, but door to imaging, imaging to tPA, and DtPA were significantly lower (p< 0.001, see table). Conclusions: 1. The establishment of a network of RCH and a tertiary center can extend the benefits of tPA to a rural population. 2. DtPA can be shortened if the ST manages the patients from arrival to the ER. This strategy could be applied to local patients if EMS notifies the ST of potential candidates for tPA.

50 Objectives: To develop a reliable method of estimation of >1/3 involvement of the middle cerebral artery territory (MCAT) on early CT scan. Background: The European Cooperative Acute Stroke Study (ECASS) suggested that > 1/3 involvement of the MCAT on early CT scan was a risk factor for symptomatic intracerebral hemorrhage (SICH) following treatment with tissue plasminogen activator (tPA) for acute ischemic stroke (AIS). There are no published guidelines on how to perform such an evaluation. The ICE method was developed for the purpose of standardizing the approach of infarct size estimation. This method requires the observer of the CT scan to mentally: 1) Idealize the MCAT into an area approximating a trapezoid, 2) Close a geometric figure around the area(s) of hypodensity(ies), and 3) Estimate the ratio of the two geometric figures (C/I). Methods: Five stroke fellows (observers) were tested with 40 CT scans which had been performed within the first few hours of an acute neurological event. Observers were blinded to patient history. They were asked whether to treat the patient on the basis of the CT scan. The decision not to treat was predicated on the presence of hemorrhage or > 1/3 MCAT involvement. Results: Five scans showed evidence of hemorrhage. All observers detected the hemorrhages. The remaining scans were of patients with presumed ischemia. Six scans were thought to show > 1/3 MCAT involvement by all observers. For all scans, median interobserver agreement among 10 paired comparisons was 86% (range 73–93%). Median kappa was 0.72 (range 0.44–0.85, pConclusion: The ICE method has very good interobserver reliability. The method merits further investigation among non-stroke physicians.

P237 Background: In the setting of acute myocardial infarction, aspirin has a significant benefit on mortality when combined with a thrombolytic. The NINDS guidelines recommend witholding antiplatelet agents (APA) for 24 hours after tPA administration for acute stroke. Post hoc analysis of the NINDS tPA study did not show worse outcomes in patients using APA prior to treatment, even though APA have a long platelet-inhibitory effect (the life of the platelet). Objective: To determine whether concomitant APA and tPA use was associated with worse outcomes. Method: We compared demographics, vascular risk factors, hemorrhagic complications, and 3 month outcomes of patients on APA at the time of their stroke with those patients not taking APA, in our prospective registry of tPA-treated patients. Results: Between 1 December 1998 and 24 July 2000, 64 patients were treated with tPA; 3 month follow-up data are available on 47 (73%). At the time of their stroke, 24 (38%) were taking APA, 40 (62%) were not. Patients taking APA were more likely to have a history of coronary heart disease, previous stroke and previous TIA, and they had higher baseline modified Rankin Scores (mRS). There was a trend for them to be older (75.3 years [APA] vs. 70.2 years [no APA], p =0.06). There was no increase in major intracranial or systemic hemorrhages at 36 hours (0% [APA] vs. 5% [no APA], p =0.54), or in mortality at 3 months (13% [APA] vs. 15% [no APA], p =1.00). More patients taking an APA had a NIH Stroke Scale score (NIHSSS) of 0–1, but this did not reach statistical significance (40% [APA] vs. 29% [no APA], p =0.42). There was a non-significant trend for fewer patients on an APA to have a 3 month mRS of 0–1 (20% [APA] vs. 41% [no APA], p =0.17). However, given their higher baseline mRS, we also looked at the percentage who returned to their baseline mRS, this favored the APA group but again it did not reach statistically significance (40% [APA] vs. 28% [no APA], p =0.38). Conclusion: Concomitant APA and tPA use appears safe and may be associated with an improved outcome. The potential beneficial effect of the combination merits further study.

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Le score ASPECT dans l'evaluation de l'infarctus >1/3 du territoire de l'artere cerebrale moyenne. Objectif: Comparer la fiabilite interobservateur. che/ des neurologues specialises dans l'accident vasculaire cerebral (AVC). pour le score ASPECT et la methode ICE (idealize-close-estimatel d'estimation de l'infarctus >1/3 du territoire de l'artere cerebrale moyenne (TACM) et determiner si le score ASPECT predit bien l'infarctus >1/3 du TACM dans l'AVC ischemique aigu. Contexte: Selon les donnees du European Cooperative Acute Stroke Study. l'atteinte >1/3 du TACM a la tomodensitometrie realisee tot apres l'evenement serait un facteur de risque de l'hemorragie intracerebrale symptomatique (HICS) suite au traitement par l'activateur du plasminogene tissulaire (t-PA) dans l'AVC ischemique aigu. mais sa fiabilite interobservateur serait mediocre (kappa 0.49) en l'absence d'une methode systematique d'estimation. La methode ICE a ete developpee pour standardiser la demarche d'estimation de la taille de l'infarctus du TACM en phase precoce et elle a une tres bonne fiabilite interobservateur (kappa 0.72). ASPECTS possede une fiabilite interobservateur comparable et on considere qu'il peut predire tant l'issue neurologique que l'HICS. Methodes: Cinq neurologues specialistes de l'AVC ont participe a l'etude de 40 tomodensitometries d'AVC ischemique aigu. Chaque neurologue a fait une evaluation independante des changements ischemiques precoces. a l'aveugle, au moyen du score ASPECT et de la methode ICE. Le standard de reference etait l'opinion majoritaire de 1/3 TACM determine par cinq neuroradiologistes. Une courbe ROC a ete etablie et des rapports de vraisemblances ont ete calcules. La concordance aleatoire corrigee (kappa) et la concordance aleatoire independante (phi) ont ete calculees pour les deux methodes et une analyse de variance a ete utilisee pour estimer la fiabilite au missel du coefficient de correlation intraclasse pour ASPECTS. Resultats: Les rapports de vraisemblances pour un test positif (>1/3 TACM) etaient extremement eleves et concluants (pres de l'infini) pour des scores ASPECT de 0 a 3; ils etaient eleves et concluants (30. 20 et 10) pour des scores ASPECT de 4. 5 et 6 respectivement: ils etaient de 1 et inutiles pour un score ASPECT de 7 et de nouveau extremement eleves et concluants (pres de zeron pour des scores ASPECT de 8 a 10. La courbe ROC suggerait qu'un point de coupe ASPECTS de moins de sept etait optimal pour estimer 1/3 TACM (sensibilite de 94% et specificite de 98%). Les statistiques kappa et phi etaient assez bonnes pour ASPECTS et ICE (0.7). Le coefficient de correlation intraclasse etait de 0.8. Conclusions: Quand des neurologues possedant une vaste experience de l'AVC utilisent une methode standard reconnues soit ASPECTS ou ICE. pour l'evaluation quantitative des changements precoces observes a la tomodensitometrie de l'AVC ischemique aigu. la concordance interobservateur et la fiabilite en sont ameliorees et sont satisfaisantes. ASPECTS permet un estime robuste et concluant de la presence de l'atteinte de 1/3 TACM et un point de coupe < 7 donne la meilleure performance.

Amelioration des resultats de la trombolyse chez les patients porteurs d'un accident vasculaire cerebral et rencontrant des criteres specifiques a l'imagerie. Introduction: Une etude du NINDS effectuee en 1995 a demontre les benefices de l'administration intraveineuse de l'activateur du plasminogene tissulaire (tPA) en phase aigue de l'accident vasculaire cerebral ischemique (AVCI). Le taux d'hemorragie intracrânienne symptomatique (HICS) dans l'etude NINDS etait de 6.4%, ce qui peut decourager certains medecins d'utiliser ce medicament. Methodes: Depuis le premier decembre 1998, les patients porteurs d'un AVCI a London, Ontario ont ete traites selon les criteres de l'etude NINDS avec une exception importante: ceux qui avaient une lesion impliquant plus d'un tiers du territoire de l'artere cerebrale moyenne reproduit par la neuro-imagerie ont ete exclus du traitement. La methode utilisee pour estimer le territoire implique porte l'acronyme ICE et avait une valeur kappa mediane de 0.80 parmi cinq medecins. Les resultats ont ete compares a ceux de l'etude NINDS. Resultats: 30 patients ont ete traites entre le premier decembre 1998 et le premier fevrier 2000. Plus de patients de London ont ete traites apres 90 minutes (p