Risk of hemorrhagic transformation with early use of direct oral anticoagulants after acute ischemic stroke: A pooled analysis of prospective studies and randomized trials.

INTRODUCTION: Precise risk of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) remains unknown, leading to delays in anticoagulation initiation for secondary stroke prevention. We sought to assess the rate of HT associated with direct oral anticoagulant (DOAC) initiation within and beyond 48 h post-AIS. METHODS: A pooled analysis of DOAC initiation within 14 days of AIS or transient ischemic attack (TIA) was conducted with six studies (four prospective open label treatment, blinded outcome studies and two randomized trials; NCT02295826 and NCT02283294). The primary endpoint was incident radiographic HT on follow-up imaging (days 7-30). Secondary endpoints included symptomatic HT, new parenchymal hemorrhage, recurrent ischemic events, extracranial hemorrhage, study period mortality, and follow-up modified Rankin Scale score. The results were reported as odds ratio (OR) or hazard ratio (HR) with 95% confidence interval (CI). RESULTS: We evaluated 509 patients; median infarct volume was 1.5 (0.1-7.8) ml, and median National Institutes of Health Stroke Scale was 2 (0-3). Incident radiographic HT was seen on follow-up scan in 34 (6.8%) patients. DOAC initiation within 48 h from index event was not associated with incident HT (adjusted OR 0.67, [0.30-1.50] P = 0.32). No patients developed symptomatic HT. Conversely, 31 (6.1%) patients developed recurrent ischemic events, 64% of which occurred within 14 days. Initiating a DOAC within 48 h of onset was associated with similar recurrent ischemic event rates compared with those in which treatment was delayed (HR: 0.42, [0.17-1.008] P = 0.052). In contrast to HT, recurrent ischemic events were associated with poor functional outcomes (OR = 6.8, [2.84-16.24], p < 0.001). CONCLUSIONS: In this pooled analysis, initiation of DOAC within 48 h post-stroke was not associated with increased incident risk of HT, and none developed symptomatic HT. The analysis was underpowered to determine the effect of early DOAC use upon recurrent ischemic events.

Factors influencing HINTS exam usage by Canadian Emergency Medicine Physicians.

OBJECTIVES: The HINTS examination (head impulse, nystagmus, test of skew) is a bedside physical examination technique that can distinguish between vertigo due to stroke, and more benign peripheral vestibulopathies. Uptake of this examination is low among Emergency Medicine (EM) physicians; therefore, we surveyed Canadian EM physicians to determine when the HINTS exam is employed, and what factors account for its low uptake. METHODS: We designed and tested a 26-question online survey, and disseminated it via email to EM physicians registered with the Canadian Association of Emergency Physicians (CAEP), with 3 and 5-week reminder emails to increase completion. This anonymous survey had no incentives for participation, and was completed by 185 EM physicians, with post-graduate medical training in either Emergency Medicine or Family Medicine. The primary outcomes were the frequencies of various responses to survey questions, with secondary outcomes being the associations between participant characteristics and given responses. RESULTS: 88 respondents (47.8%) consistently use the HINTS examination in the work-up of vertigo, and 117 (63.7%) employ it in scenarios where its clinical utility is limited. The latter is more common among physicians working in non-academic settings, without 5-year EM residency training, and with greater years of practice (p < 0.01). The most frequent explanations for non-use were a lack of need for the HINTS examination, the lack of validation of the exam among EM physicians, and concerns surrounding the head-impulse test. CONCLUSIONS: Though HINTS exam usage is common, there is a need for education on when to apply it, and how to do so, particularly as concerns the head-impulse test. Our attached rubric may assist with this, but quality-improvement initiatives are warranted. Low uptake is partly due to the lack of validation of this examination among EM physicians, so effort should be made to conduct well-designed HINTS trials exclusively involving EM physicians.

RéSUMé: OBJECTIFS: L'examen HINTS (head impulse, nystagmus, test of skew) est une technique d'examen physique au chevet du patient qui permet de distinguer les vertiges dus à un accident vasculaire cérébral des vestibulopathies périphériques plus bénignes. Cet examen est peu pratiqué par les médecins en médecine d'urgence (MU). Nous avons donc mené une enquête auprès des médecins d'urgence canadiens afin de déterminer quand l'examen HINTS est utilisé et quels sont les facteurs qui expliquent sa faible utilisation. MéTHODES: Nous avons conçu et testé une enquête en ligne de 26 questions, et l'avons diffusée par courriel aux médecins urgentistes inscrits à l'Association canadienne des médecins d'urgence (ACMU), avec des courriels de rappel de trois et cinq semaines pour augmenter le taux de réponse. Cette enquête anonyme, qui ne comportait aucune incitation à la participation, a été remplie par 185 médecins de médecine d'urgence ayant suivi une formation médicale postuniversitaire en médecine d'urgence ou en médecine familiale. Les résultats primaires étaient les fréquences des diverses réponses aux questions de l'enquête, les résultats secondaires étant les associations entre les caractéristiques des participants et les réponses données. RéSULTATS: 88 répondants (47,8 %) utilisent systématiquement l'examen HINTS dans l'évaluation des vertiges, et 117 (63,7 %) l'emploient dans des scénarios où son utilité clinique est limitée. Cette dernière est plus fréquente chez les médecins travaillant dans des établissements non universitaires, n'ayant pas suivi une formation de 5 ans en résidence en médecine d'urgence et ayant un plus grand nombre d'années de pratique (p < 0,01). Les explications les plus fréquentes de la non-utilisation étaient le manque de nécessité de l'examen HINTS, le manque de validation de l'examen parmi les médecins de médecine d'urgence et les préoccupations concernant le test d'impulsion de la tête. CONCLUSIONS: Bien que l'utilisation de l'examen HINTS soit courante, il existe un besoin d'éducation sur le moment où il faut l'appliquer et sur la manière de le faire, en particulier en ce qui concerne le test d'impulsion de la tête. Notre rubrique ci-jointe peut vous aider à cet égard, mais des initiatives d'amélioration de la qualité sont justifiées. Le faible taux d'utilisation est en partie dû au manque de validation de cet examen parmi les médecins de la médecine d'urgence. Il faut donc s'efforcer de mener des essais HINTS bien conçus impliquant exclusivement des médecins de la médecine d'urgence.

Pre- and post-stroke oral antithrombotics and mortality in patients with ischaemic stroke.

BACKGROUND: Reducing stroke occurrence requires the effective management of cardiovascular and other stroke risk factors. PURPOSE: To describe pre- and post-stroke medication use, focusing on antithrombotic therapy and mortality risk, in individuals hospitalised for ischaemic stroke (IS) in the United Kingdom. METHOD: Using primary care electronic health records from the United Kingdom, we identified patients hospitalised for IS (July 2016-September 2019) and classed them into three groups: atrial fibrillation (AF) diagnosed pre-stroke, AF diagnosed post-stroke, and non-AF stroke (no AF diagnosed pre-/post-stroke). We determined use of cardiovascular medications in the 90 days pre- and post-stroke and calculated mortality rates. RESULTS: There were 3201 hospitalised IS cases: 76.2% non-AF stroke, 15.7% AF pre-stroke, and 8.1% AF post-stroke. Oral anticoagulant (OAC) use increased between the pre- and post-stroke periods as follows: 54.3%-78.7% (AF pre-stroke group), 2.3%-84.8% (AF post-stroke group), and 3.4%-7.3% (non-AF stroke group). Corresponding increases in antiplatelet use were 30.8%-35.4% (AF pre-stroke group) 38.5%-47.5% (AF post-stroke group), and 37.5%-87.3% (non-AF stroke group). Among all IS cases, antihypertensive use increased from 66.8% pre-stroke to 78.8% post-stroke; statin use increased from 49.6%-85.2%. Mortality rates per 100 person-years (95% CI) were 17.30 (14.70-20.35) in the AF pre-stroke group and 9.65 (8.81-10.56) among all other stroke cases. CONCLUSION: Our findings identify areas for improvement in clinical practice, including optimising the level of OAC prescribing to patients with known AF, which could potentially help reduce the future burden of stroke.

Functional Abilities of an International Post-Stroke Population: Standard Assessment of Global Everyday Activities (SAGEA) Scale.

BACKGROUND AND OBJECTIVES: Function is an important outcome after stroke; traditional assessments may not capture functional deficits important to patients. We examined the validity of the Standard Assessment of Global Everyday Activities (SAGEA), a patient-reported outcome that assesses activities important to patients and for use in international clinical trials. METHODS: The NAVIGATE-ESUS trial evaluated rivaroxaban compared to aspirin in preventing recurrent stroke in 7213 participants. The Modified Rankin Scale (mRS), the National Institutes of Health Stroke Scale (NIHSS), and the SAGEA were collected at entry. Chi square tests were used to compare proportions and Spearman rank correlations were used to compare between measures. SAGEA was compared to the Modified Frailty Index (MFI) and the occurrence of infarct to examine criterion validity RESULTS: Participants were 67 years, 2/3 were male, and at baseline 30% had no disability and 58% had slight disability according to mRS scores. SAGEA was weakly correlated with the mRS (r=0.37), the NIHSS (r=0.29) and the MFI (r=0.30). Of the 2154 with an mRS score of 0, 61% reported difficulty on the SAGEA. The largest discrepancies between SAGEA and other measures were because of cognitive functional deficits detected by the SAGEA that were not identified on other assessments. A larger number of MRI identified infarcts (acute and covert) were associated with a higher SAGEA score (p=0.007). CONCLUSIONS: The SAGEA is a simple, globally applicable measure of cognitive and functional abilities that identifies issues that other commonly used assessments of disability and function do not capture.

Trends in Incidence of Intracerebral Hemorrhage and Association With Antithrombotic Drug Use in Denmark, 2005-2018.

Importance: Spontaneous (nontraumatic) intracerebral hemorrhage (ICH) is the most severe complication of antithrombotic drug use. Objectives: To estimate the strength of association between use of antithrombotic drugs and risk of ICH and to examine major changes in the incidence of ICH in the general population. Design, Setting, and Participants: This case-control study of patients with a first-ever ICH from January 1, 2005, to December 31, 2018, matched by age, sex, and calendar year with general population controls (1:40 ratio), assessed case and control patients 20 to 99 years of age in population-based nationwide registries in Denmark (population of 5.8 million). Exposures: Use of low-dose aspirin, clopidogrel, a vitamin K antagonist (VKA), or a direct oral anticoagulant (DOAC). Main Outcomes and Measures: Association of ICH with antithrombotic drug use, annual age- and sex-standardized incidence rate of ICH, and prevalence of treatment with antithrombotic drugs. Conditional logistic regression models estimated adjusted odds ratios (aORs) (95% CIs) for the association of antithrombotic drugs with ICH. Results: Among 16 765 cases with ICH (mean [SD] age, 72.8 [13.1] years; 8761 [52.3%] male), 7473 (44.6%) were exposed to antithrombotic medications at the time of ICH onset. The association with ICH was weakest for current use of low-dose aspirin (cases: 28.7%, controls: 22.6%; aOR, 1.51; 95% CI, 1.44-1.59) and clopidogrel (cases: 6.2%, controls: 3.4%; aOR, 1.65; 95% CI, 1.47-1.84) and strongest with current use of a VKA (cases: 12.0%, controls: 5.0%; aOR, 2.76; 95% CI, 2.58-2.96). The association with ICH was weaker for DOACs (cases: 3.0%, controls: 1.8%; aOR, 1.83; 95% CI, 1.61-2.07) than for VKAs. Compared with 2005, the prevalence of use of oral anticoagulants among general population controls in 2018 was higher (3.8% vs 11.1%), predominantly because of increased use of DOACs (DOACs: 0% vs 7.0%; VKA: 3.8% vs 4.2%). Antiplatelet drugs were used less frequently (24.7% vs 21.4%) because of decreased use of low-dose aspirin (24.3% vs 15.3%), whereas clopidogrel use increased (1.0% vs 6.8%). The age- and sex-standardized incidence rate of ICH decreased from 33 per 100 000 person-years in 2005 to 24 per 100 000 person-years in 2018 (P < .001 for trend). Conclusions and Relevance: In Denmark from 2005 to 2018, use of antithrombotic drugs, especially VKAs, was associated with ICH. Although use of oral anticoagulation increased substantially during the study period, the incidence rate of ICH decreased.

The Relationship Between Glucose Control and Cognitive Function in People With Diabetes After a Lacunar Stroke.

CONTEXT: Lacunar strokes and diabetes are risk factors for cognitive dysfunction. Elucidating modifiable risk factors for cognitive dysfunction has great public health implications. One factor may be glycemic status, as measured by glycated hemoglobin (A1c). OBJECTIVE: The aim of this study was to assess the relationship between A1c and cognitive function in lacunar stroke patients with diabetes. METHODS: The effect of baseline and follow-up A1c on the baseline and the change in Cognitive Assessment Screening Instrument (CASI) score over time among participants with a median of 2 cognitive assessments (range, 1-5) was examined in 942 individuals with diabetes and a lacunar stroke who participated in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial (ClinicalTrials.gov No. NCT00059306). RESULTS: Every 1% higher baseline A1c was associated with a 0.06 lower standardized CASI z score (95% CI, -0.101 to -0.018). Higher baseline A1c values were associated with lower CASI z scores over time (P for interaction = .037). A 1% increase in A1c over time corresponded with a CASI score decrease of 0.021 (95% CI, -0.0043 to -0.038) during follow-up. All these remained statistically significant after adjustment for age, sex, education, race, depression, hypertension, hyperlipidemia, body mass index, cardiovascular disease, obstructive sleep apnea, diabetic retinopathy, nephropathy insulin use, and white-matter abnormalities. CONCLUSION: This analysis of lacunar stroke patients with diabetes demonstrates a relationship between A1c and change in cognitive scores over time. Intervention studies are needed to delineate whether better glucose control could slow the rate of cognitive decline in this high-risk population.

Discontinuation of oral anticoagulation in atrial fibrillation and risk of ischaemic stroke.

OBJECTIVE: To evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF). METHODS: We undertook a population-based cohort study with nested case-control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016-2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression. RESULTS: We identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued. CONCLUSIONS: Our results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.

Early Dabigatran Treatment After Transient Ischemic Attack and Minor Ischemic Stroke Does Not Result in Hemorrhagic Transformation.

OBJECTIVES: The optimal timing of anticoagulation after ischemic stroke in atrial fibrillation (AF) patients is unknown. Our aim was to demonstrate the feasibility and safety of initiating dabigatran therapy within 14 days of transient ischemic attack (TIA) or minor stroke in AF patients. PATIENTS AND METHODS: A prospective, multi-center registry (NCT02415855) in patients with AF treated with dabigatran within 14 days of acute ischemic stroke/TIA (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) onset. Baseline and follow-up computed tomography (CT) scans were assessed for hemorrhagic transformation (HT) and graded by using European Cooperative Acute Stroke Study criteria. RESULTS: One hundred and one patients, with a mean age of 72.4 ± 11.5 years, were enrolled. Median infarct volume was 0 ml. Median time from index event onset to dabigatran initiation was 2 days, and median baseline NIHSS was 1. Pre-treatment HT was present in seven patients. No patients developed symptomatic HT. On the day 7 CT scan, HT was present in six patients (one progressing from baseline hemorrhagic infarction type 1). Infarct volume was a predictor of incident HT (odds ratio = 1.063 [1.020-1.107], p < 0.003). All six (100%) patients with new/progressive HT were functionally independent (modified Rankin Scale (mRS) = 0-2) at 30 days, which was similar to those without HT (90%, p = 0.422). Recurrent ischemic events occurred within 30 days in four patients, two of which were associated with severe disability and death (mRS 5 and 6, respectively). CONCLUSION: Early dabigatran treatment did not precipitate symptomatic HT after minor stroke. Asymptomatic HT was associated with larger baseline infarct volumes. Early recurrent ischemic events may be clinically more important.

Dabigatran Treatment of Acute Noncardioembolic Ischemic Stroke.

Background and Purpose- Patients with transient ischemic attack (TIA) and minor ischemic stroke are at risk for early recurrent cerebral ischemia. Anticoagulants are associated with reduced recurrence but also increased hemorrhagic transformation (HT). The safety of the novel oral anticoagulant dabigatran in acute stroke has not been evaluated. Methods- DATAS II (Dabigatran Treatment of Acute Stroke II) was a phase II prospective, randomized open label, blinded end point trial. Patients with noncardioembolic stroke/transient ischemic attack (National Institutes of Health Stroke Scale score, ≤9; infarct volume, ≤25 mL) were randomized to dabigatran or aspirin. Magnetic resonance imaging was performed before randomization and repeated at day 30. Imaging end points were ascertained centrally by readers blinded to treatment. The primary end point was symptomatic HT within 37 days of randomization. Results- A total of 305 patients, mean age 66.59±13.21 years, were randomized to dabigatran or aspirin a mean of 42.00±17.31 hours after symptom onset. The qualifying event was a transient ischemic attack in 21%, and ischemic stroke in 79% of patients. Median National Institutes of Health Stroke Scale (interquartile range) was 1 (0-2), and mean infarct volume 3.2±6.5 mL. No symptomatic HT occurred. Asymptomatic petechial HT developed in 11/142 (7.8%) of dabigatran-assigned patients and 5/142 (3.5%) of aspirin-assigned patients (relative risk, 2.301 [95% CI, 0.778-6.802]). Baseline infarct volume predicted incident HT (odds ratio, 1.07 [95% CI, 1.03-1.12]; P=0.0026). Incident covert infarcts on day 30 imaging occurred in 9/142 (6.3%) of dabigatran-assigned and 14/142 (9.8%) of aspirin-assigned patients (relative risk, 0.62 [95% CI, 0.26, 1.48]). Conclusions- Dabigatran was associated with a risk of HT similar to aspirin in acute minor noncardioembolic ischemic stroke/transient ischemic attack. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02295826.

Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table.

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke.

Are large simple trials for dementia prevention possible?

New trials of dementia prevention are needed to test novel strategies and agents. Large, simple, cardiovascular trials have successfully discovered treatments with moderate but worthwhile effects to prevent heart attack and stroke. The design of these trials may hold lessons for the dementia prevention. Here we outline suitable populations, interventions and outcomes for large simple trials in dementia prevention. We consider what features are needed to maximise efficiency. Populations could be selected by age, clinical or genetic risk factors or clinical presentation. Patients and their families prioritise functional and clinical outcomes over cognitive scores and levels of biomarkers. Loss of particular functions or dementia diagnoses therefore are most meaningful to participants and potential patients and can be measured in large trials. The size of the population and duration of follow-up needed for dementia prevention trials will be a major challenge and will need collaboration between many clinical investigators, funders and patient organisations.

2018 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in atrial fibrillation (AF) management. This 2018 Focused Update addresses: (1) anticoagulation in the context of cardioversion of AF; (2) the management of antithrombotic therapy for patients with AF in the context of coronary artery disease; (3) investigation and management of subclinical AF; (4) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (5) acute pharmacological cardioversion of AF; (6) catheter ablation for AF, including patients with concomitant AF and heart failure; and (7) an integrated approach to the patient with AF and modifiable cardiovascular risk factors. The recommendations were developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards. Individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included as Supplementary Material and are available on the CCS Web site. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF guidelines recommendations, from 2010 to the present 2018 Focused Update, which is provided in the Supplementary Material.

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

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

Atraumatic versus traumatic lumbar puncture needles: a systematic review and meta-analysis protocol.

INTRODUCTION: Lumbar puncture is one of the oldest and most commonly performed procedures in medicine, used to diagnose and treat disease. Headache following lumbar puncture remains a frequent complication, causing significant patient discomfort and often requiring narcotic analgesia or invasive therapy. Needle tip design has been proposed to affect the incidence of headache postlumbar puncture, with pencil-point 'atraumatic' needles thought to reduce its incidence in comparison to bevelled 'traumatic' needles. Despite this, the use of atraumatic needles and knowledge of their existence remains significantly limited among clinicians. This study will systematically review the evidence on atraumatic lumbar puncture needles and compare them with traumatic needles across a variety of clinical outcomes. METHODS AND ANALYSES: We will include published randomised controlled trials (RCTs), observational studies and abstracts, with no publication type or language restrictions. Search strategies will be designed to peruse the MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CINAHL, WHO Clinical Trials Database and Cochrane Library databases. We will also implement strategies to search the grey literature. 3 reviewers will thoroughly and independently examine the search results, complete data abstraction and conduct quality assessment. Included RCTs will be assessed using the Cochrane risk of bias assessment tool and eligible observational studies will be examined using the Newcastle-Ottawa Scale. We will examine the outcomes of: headache and its type, intensity, duration and treatment; backache; success rate; hearing disturbance and nerve root irritation. The primary outcome will be the incidence of postdural puncture headache. We will calculate pooled estimates, relative risks for dichotomous outcomes and weighted mean differences for continuous outcomes, with corresponding 95% CIs. Statistical heterogeneity will be measured using Cochran's Q test and quantified using the I2 statistic. We will also conduct prespecified subgroup and sensitivity analyses to examine if covariates exist and to explore potential heterogeneity. ETHICS AND DISSEMINATION: Research ethics board approval is not required for this study as it draws from published data and raises no concerns related to patient privacy. This review will provide a comprehensive assessment of the evidence on atraumatic needles for lumbar puncture and is directed to a wide audience. Results from the review will be disseminated extensively through conferences and submitted to a peer-reviewed journal for publication. TRIAL REGISTRATION NUMBER: CRD42016047546.

2016 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation.

The Canadian Cardiovascular Society (CCS) Atrial Fibrillation (AF) Guidelines Committee provides periodic reviews of new data to produce focused updates that address clinically important advances in AF management. This 2016 Focused Update deals with: (1) the management of antithrombotic therapy for AF patients in the context of the various clinical presentations of coronary artery disease; (2) real-life data with non-vitamin K antagonist oral anticoagulants; (3) the use of antidotes for the reversal of non-vitamin K antagonist oral anticoagulants; (4) digoxin as a rate control agent; (5) perioperative anticoagulation management; and (6) AF surgical therapy including the prevention and treatment of AF after cardiac surgery. The recommendations were developed with the same methodology used for the initial 2010 guidelines and the 2012 and 2014 Focused Updates. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) standards, individual studies and literature were reviewed for quality and bias; the literature review process and evidence tables are included in the Supplementary Material, and on the CCS Web site. The section on concomitant AF and coronary artery disease was developed in collaboration with the CCS Antiplatelet Guidelines Committee. Details of the updated recommendations are presented, along with their background and rationale. This document is linked to an updated summary of all CCS AF Guidelines recommendations, from 2010 to the present 2016 Focused Update.

Potential Cost-Effectiveness of Ambulatory Cardiac Rhythm Monitoring After Cryptogenic Stroke.

BACKGROUND AND PURPOSE: Prolonged ambulatory ECG monitoring after cryptogenic stroke improves detection of covert atrial fibrillation, but its long-term cost-effectiveness is uncertain. METHODS: We estimated the cost-effectiveness of noninvasive ECG monitoring in patients aged ≥55 years after a recent cryptogenic stroke and negative 24-hour ECG. A Markov model used observed rates of atrial fibrillation detection and anticoagulation from a randomized controlled trial (EMBRACE) and the published literature to predict lifetime costs and effectiveness (ischemic strokes, hemorrhages, life-years, and quality-adjusted life-years [QALYs]) for 30-day ECG (primary analysis) and 7-day or 14-day ECG (secondary analysis), when compared with a repeat 24-hour ECG. RESULTS: Prolonged ECG monitoring (7, 14, or 30 days) was predicted to prevent more ischemic strokes, decrease mortality, and improve QALYs. If anticoagulation reduced stroke risk by 50%, 30-day ECG (at a cost of USD $447) would be highly cost-effective ($2000 per QALY gained) for patients with a 4.5% annual ischemic stroke recurrence risk. Cost-effectiveness was sensitive to stroke recurrence risk and anticoagulant effectiveness, which remain uncertain, especially at higher costs of monitoring. Shorter duration (7 or 14 days) monitoring was cost saving and more effective than an additional 24-hour ECG; its cost-effectiveness was less sensitive to changes in ischemic stroke risk and treatment effect. CONCLUSIONS: After a cryptogenic stroke, 30-day ECG monitoring is likely cost-effective for preventing recurrent strokes; 14-day monitoring is an attractive value alternative, especially for lower risk patients. These results strengthen emerging recommendations for prolonged ECG monitoring in secondary stroke prevention. Cost-effectiveness in practice will depend on careful patient selection.

Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis.

BACKGROUND AND PURPOSE: A limitation when making early decisions on stroke management is the lack of rapid diagnostic and prognostic testing. Our study sought to identify peripheral blood RNA biomarkers associated with stroke. The secondary aims were to assess the discriminative capacity of RNA biomarkers for primary stroke type and stroke prognosis at 1-month. METHODS: Whole-blood gene expression profiling was conducted on the discovery cohort: 129 first-time stroke cases that had blood sampling within 5 days of symptom onset and 170 control participants with no history of stroke. RESULTS: Through multiple regression analysis, we determined that expression of the gene MCEMP1 had the strongest association with stroke of 11 181 genes tested. MCEMP1 increased by 2.4-fold in stroke when compared with controls (95% confidence interval, 2.0-2.8; P=8.2×10(-22)). In addition, expression was elevated in intracerebral hemorrhage when compared with ischemic stroke cases (P=3.9×10(-4)). MCEMP1 was also highest soon after symptom onset and had no association with stroke risk factors. Furthermore, MCEMP1 expression independently improved discrimination of 1-month outcome. Indeed, discrimination models for disability and mortality that included MCEMP1 expression, baseline modified Rankin Scale score, and primary stroke type improved discrimination when compared with a model without MCEMP1 (disability Net Reclassification Index, 0.76; P=3.0×10(-6) and mortality Net Reclassification Index, 1.3; P=1.1×10(-9)). Significant associations with MCEMP1 were confirmed in an independent validation cohort of 28 stroke cases and 34 controls. CONCLUSIONS: This study demonstrates that peripheral blood expression of MCEMP1 may have utility for stroke diagnosis and as a prognostic biomarker of stroke outcome at 1-month.

Impact of disability status on ischemic stroke costs in Canada in the first year.

BACKGROUND: Longitudinal, patient-level data on resource use and costs after an ischemic stroke are lacking in Canada. The objectives of this analysis were to calculate costs for the first year post-stroke and determine the impact of disability on costs. METHODOLOGY: The Economic Burden of Ischemic Stroke (BURST) Study was a one-year prospective study with a cohort of ischemic stroke patients recruited at 12 Canadian stroke centres. Clinical history, disability, health preference and resource utilization information was collected at discharge, three months, six months and one year. Resources included direct medical costs (2009 CAN$) such as emergency services, hospitalizations, rehabilitation, physician services, diagnostics, medications, allied health professional services, homecare, medical/assistive devices, changes to residence and paid caregivers, as well as indirect costs. Results were stratified by disability measured at discharge using the modified Rankin Score (mRS): non-disabling stroke (mRS 0-2) and disabling stroke (mRS 3-5). RESULTS: We enrolled 232 ischemic stroke patients (age 69.4 ± 15.4 years; 51.3% male) and 113 (48.7%) were disabled at hospital discharge. The average annual cost was $74,353; $107,883 for disabling strokes and $48,339 for non-disabling strokes. CONCLUSIONS: An average annual cost for ischemic stroke was calculated in which a disabling stroke was associated with a two-fold increase in costs compared to NDS. Costs during the hospitalization to three months phase were the highest contributor to the annual cost. A "back of the envelope" calculation using 38,000 stroke admissions and the average annual cost yields $2.8 billion as the burden of ischemic stroke.