Stavroula Raptis

IScore A Risk Score to Predict Death Early After Hospitalization for an Acute Ischemic Stroke

Background— A predictive model of stroke mortality may be useful for clinicians to improve communication with and care of hospitalized patients. Our aim was to identify predictors of mortality and to develop and validate a risk score model using information available at hospital presentation. Methods and Results— This retrospective study included 12 262 community-based patients presenting with an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003 and 2008 who had been identified from the Registry of the Canadian Stroke Network (8223 patients in the derivation cohort, 4039 in the internal validation cohort) and the Ontario Stroke Audit (3720 for the external validation cohort). The mortality rates for the derivation and internal validation cohorts were 12.2% and 12.6%, respectively, at 30 days and 22.5% and 22.9% at 1 year. Multivariable predictors of 30-day and 1-year mortality included older age, male sex, severe stroke, nonlacunar stroke subtype, glucose ≥7.5 mmol/L (135 mg/dL), history of atrial fibrillation, coronary artery disease, congestive heart failure, cancer, dementia, kidney disease on dialysis, and dependency before the stroke. A risk score index stratified the risk of death and identified low- and high- risk individuals. The c statistic was 0.850 for 30-day mortality and 0.823 for 1-year mortality for the derivation cohort, 0.851 for the 30-day model and 0.840 for the 1-year mortality model in the internal validation set, and 0.790 for the 30-day model and 0.782 for the 1-year model in the external validation set. Conclusion— Among patients with ischemic stroke, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The predictive score may assist clinicians in estimating stroke mortality risk and policymakers in providing a quantitative tool to compare facilities.

The iScore Predicts Poor Functional Outcomes Early After Hospitalization for an Acute Ischemic Stroke

Background and Purpose— The iScore is a prediction tool originally developed to estimate the risk of death after hospitalization for an acute ischemic stroke. Our objective was to determine whether the iScore could also predict poor functional outcomes. Methods— We applied the iScore to patients presenting with an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003 and 2008, who had been identified from the Registry of the Canadian Stroke Network regional stroke center database (n=3818) and from an external data set, the Registry of the Canadian Stroke Network Ontario Stroke Audit (n=4635). Patients were excluded if they were included in the sample used to develop and validate the initial iScore. Poor functional outcomes were defined as: (1) death at 30 days or disability at discharge, in which disability was defined as having a modified Rankin Scale 3 to 5; and (2) death at 30 days or institutionalization at discharge. Results— The prevalence of poor functional outcomes in the Registry of the Canadian Stroke Network and the Ontario Stroke Audit, respectively, were 55.7% and 44.1% for death at 30 days or disability at discharge and 16.9% and 16.2%, respectively, for death at 30 days or institutionalization at discharge. The iScore stratified the risk of poor outcomes in low- and high-risk individuals. Observed versus predicted outcomes showed high correlations: 0.988 and 0.940 for mortality or disability and 0.985 and 0.993 for mortality or institutionalization in the Registry of the Canadian Stroke Network and Ontario Stroke Audit cohorts. Conclusions— The iScore can be used to estimate the risk of death or a poor functional outcome after an acute ischemic stroke.

Care and outcomes in patients with ischemic stroke with and without preexisting dementia

Objective: To describe clinical characteristics and evaluate processes of care and outcomes at discharge in patients with ischemic stroke with and without preexisting dementia. Methods: Retrospective cohort study using the Registry of the Canadian Stroke Network including patients presenting with an acute ischemic stroke between 2003 and 2008. Preexisting dementia was defined as any type of dementia that was present prior to the index stroke case. Palliative patients were excluded. Demographic information, clinical presentation, selected process measures (e.g., thrombolysis, admission to stroke unit, carotid imaging, stroke prevention), pneumonia, death, disability, and disposition at discharge were analyzed. Results: Among 9,304 eligible patients with an acute ischemic stroke, 702 (9.1%) had a history of dementia. Patients with dementia were older (mean age 81 vs 70 years; p < 0.001), had more severe strokes (Canadian Neurological Scale score <4, 20.7% vs 10.5%; p < 0.001), and were more likely to have atrial fibrillation (22.8% vs 15.3%; p < 0.001) than those without dementia. Patients with dementia were slightly less likely to be admitted to a stroke unit (63% vs 67.6%; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70–0.96) or to receive thrombolysis (10.5% vs 15.7%; OR 0.63, 95% CI 0.49–0.81). There were no differences in other performance measures. Patients with preexisting dementia had higher disability at discharge (OR 3.20, 95% CI 2.64–3.87) and were less likely to be discharged to their prestroke place of residence (24% vs 45%; p < 0.001). Conclusions: In patients with stroke, preexisting dementia is associated with high rates of disability and institutionalization, representing an increasing challenge for the health care system.

JURaSSiC Accuracy of clinician vs risk score prediction of ischemic stroke outcomes

Objective: We compared the accuracy of clinicians and a risk score (iScore) to predict observed outcomes following an acute ischemic stroke. Methods: The JURaSSiC (Clinician JUdgment vs Risk Score to predict Stroke outComes) study assigned 111 clinicians with expertise in acute stroke care to predict the probability of outcomes of 5 ischemic stroke case scenarios. Cases (n = 1,415) were selected as being representative of the 10 most common clinical presentations from a pool of more than 12,000 stroke patients admitted to 12 stroke centers. The primary outcome was prediction of death or disability (modified Rankin Scale [mRS] ≥3) at discharge within the 95% confidence interval (CI) of observed outcomes. Secondary outcomes included 30-day mortality and death or institutionalization at discharge. Results: Clinicians made 1,661 predictions with overall accuracy of 16.9% for death or disability at discharge, 46.9% for 30-day mortality, and 33.1% for death or institutionalization at discharge. In contrast, 90% of the iScore-based estimates were within the 95% CI of observed outcomes. Nearly half (n = 53 of 111; 48%) of participants were unable to accurately predict the probability of the primary outcome in any of the 5 rated cases. Less than 1% (n = 1) provided accurate predictions in 4 of the 5 cases and none accurately predicted all 5 case outcomes. In multivariable analyses, the presence of patient characteristics associated with poor outcomes (mRS ≥3 or death) in previous studies (older age, high NIH Stroke Scale score, and nonlacunar subtype) were associated with more accurate clinician predictions of death at 30 days (odds ratio [OR] 2.40, 95% CI 1.57–3.67) and with a trend for more accurate predictions of death or disability at discharge (OR 1.85, 95% CI 0.99–3.46). Conclusions: Clinicians with expertise in stroke performed poorly compared to a validated tool in predicting the outcomes of patients with an acute ischemic stroke. Use of the risk stroke outcome tool may be superior for decision-making following an acute ischemic stroke.Objective: We compared the accuracy of clinicians and a risk score (iScore) to predict observed outcomes following an acute ischemic stroke. Methods: The JURaSSiC (Clinician JUdgment vs Risk Score to predict Stroke outComes) study assigned 111 clinicians with expertise in acute stroke care to predict the probability of outcomes of 5 ischemic stroke case scenarios. Cases (n = 1,415) were selected as being representative of the 10 most common clinical presentations from a pool of more than 12,000 stroke patients admitted to 12 stroke centers. The primary outcome was prediction of death or disability (modified Rankin Scale [mRS] ≥3) at discharge within the 95% confidence interval (CI) of observed outcomes. Secondary outcomes included 30-day mortality and death or institutionalization at discharge. Results: Clinicians made 1,661 predictions with overall accuracy of 16.9% for death or disability at discharge, 46.9% for 30-day mortality, and 33.1% for death or institutionalization at discharge. In contrast, 90% of the iScore-based estimates were within the 95% CI of observed outcomes. Nearly half (n = 53 of 111; 48%) of participants were unable to accurately predict the probability of the primary outcome in any of the 5 rated cases. Less than 1% (n = 1) provided accurate predictions in 4 of the 5 cases and none accurately predicted all 5 case outcomes. In multivariable analyses, the presence of patient characteristics associated with poor outcomes (mRS ≥3 or death) in previous studies (older age, high NIH Stroke Scale score, and nonlacunar subtype) were associated with more accurate clinician predictions of death at 30 days (odds ratio [OR] 2.40, 95% CI 1.57–3.67) and with a trend for more accurate predictions of death or disability at discharge (OR 1.85, 95% CI 0.99–3.46). Conclusions: Clinicians with expertise in stroke performed poorly compared to a validated tool in predicting the outcomes of patients with an acute ischemic stroke. Use of the risk stroke outcome tool may be superior for decision-making following an acute ischemic stroke.

Research Recruitment Practices and Critically Ill Patients. A Multicenter, Cross-Sectional Study (The Consent Study)

RATIONALE Limited cross-sectional data exist to characterize the challenges of enrolling critically ill patients into research studies. OBJECTIVES We aimed to describe recruitment practices, document factors that impact recruitment, and identify factors that may enhance future research feasibility. METHODS We conducted a prospective, observational study of all critically ill adults eligible to participate in research studies at 23 Canadian intensive care units. We characterized eligibility events into one of five consent outcomes, identified reasons why opportunities to recruit were missed or infeasible, and documented decision makers rationale for providing or declining consent. MEASUREMENTS AND MAIN RESULTS Patients made decisions for themselves in 8.9% of encounters. In 452 eligibility events, consent was not required in 14 (3.1%), missed in 130 (28.8%), infeasible due to operational reasons in 129 (28.5%), obtained in 140 (31.0%), and declined in 39 (8.6%). More than half (57.3%) of all opportunities to recruit patients were missed or infeasible, largely because of research team workload, limited availability, narrow time windows for inclusion, difficulties in contacting families, nonexistent substitute decision makers (SDMs), physician refusals, and protocols prohibiting coenrollment. The rationale for providing consent differed between patients and SDMs. Greater research coordinator experience and site research volume and broader time windows for inclusion were significant predictors of fewer declined consents. CONCLUSIONS A large gap exists between eligibility and the frequency with which consent encounters occur in intensive care unit research. Recruitment is susceptible to design and procedural inefficiencies that hinder recruitment and to personnel availability, given the need to interact with SDMs. Current enrollment practices may underrepresent potential study populations.

Genetic instability in human tumors

Genetic, or genomic, instability refers to a series of observed spontaneous genetic changes occurring at an accelerated rate in cell populations derived from the same ancestral precursor. This is far from a new finding, but is one that has increasingly gained more attention in the last decade due to its plausible role(s) in tumorigenesis. The majority of genetic alterations contributing to the malignant transformation are seen in growth regulatory genes, and in genes involved in cell cycle progression and arrest. Genomic instability may present itself through alterations in the length of short repeat stretches of coding and non-coding DNA, resulting in microsatellite instability. Tumors with such profiles are referred to as exhibiting a mutator phenotype, which is largely a consequence of inactivating mutations in DNA damage repair genes. Genomic instability may also, and most commonly, results from gross chromosomal changes, such as translocations or amplifications, which lead to chromosomal instability. Telomere length and telomerase activity, important in maintaining chromosomal structure and in regulating a normal cells lifespan, have been shown to have a function in both suppressing and facilitating malignant transformation. In addition to such direct sequence and structural changes, gene silencing through the hypermethylation of promoter regions, or increased gene expression through the hypomethylation of such regions, together, form an alternative, epigenetic mechanism leading to instability. Emerging evidence also suggests that dietary and environmental agents can further modulate the contribution of genetic instability to tumorigenesis. Currently, there is still much debate over the distinct classes of genomic instability and their specific roles in the initiation of tumor formation, as well as in the progressive transition to a cancerous state. This review examines the various molecular mechanisms that result in this genomic instability and the potential contribution of the latter to human carcinogenesis.

Specific Variants in the MLH1 Gene Region May Drive DNA Methylation, Loss of Protein Expression, and MSI-H Colorectal Cancer

Background We previously identified an association between a mismatch repair gene, MLH1, promoter SNP (rs1800734) and microsatellite unstable (MSI-H) colorectal cancers (CRCs) in two samples. The current study expanded on this finding as we explored the genetic basis of DNA methylation in this region of chromosome 3. We hypothesized that specific polymorphisms in the MLH1 gene region predispose it to DNA methylation, resulting in the loss of MLH1 gene expression, mismatch-repair function, and consequently to genome-wide microsatellite instability. Methodology/Principal Findings We first tested our hypothesis in one sample from Ontario (901 cases, 1,097 controls) and replicated major findings in two additional samples from Newfoundland and Labrador (479 cases, 336 controls) and from Seattle (591 cases, 629 controls). Logistic regression was used to test for association between SNPs in the region of MLH1 and CRC, MSI-H CRC, MLH1 gene expression in CRC, and DNA methylation in CRC. The association between rs1800734 and MSI-H CRCs, previously reported in Ontario and Newfoundland, was replicated in the Seattle sample. Two additional SNPs, in strong linkage disequilibrium with rs1800734, showed strong associations with MLH1 promoter methylation, loss of MLH1 protein, and MSI-H CRC in all three samples. The logistic regression model of MSI-H CRC that included MLH1-promoter-methylation status and MLH1 immunohisotchemistry status fit most parsimoniously in all three samples combined. When rs1800734 was added to this model, its effect was not statistically significant (P-value  = 0.72 vs. 2.3×10−4 when the SNP was examined alone). Conclusions/Significance The observed association of rs1800734 with MSI-H CRC occurs through its effect on the MLH1 promoter methylation, MLH1 IHC deficiency, or both.

A Prescription at Discharge Improves Long-term Adherence for Secondary Stroke Prevention

BACKGROUND Medication adherence is important for optimal secondary stroke prevention. We evaluated short-term adherence to antihypertensive and lipid-lowering agents after a new ischemic stroke, as predictor of adherence at 1 and 2 years. METHODS A 5-year cohort of patients from 11 institutions in the Registry of the Canadian Stroke Network was linked to population-based administrative health records. Patients diagnosed with acute ischemic stroke and discharged home were included. Medication adherence was assessed through documented prescription filling at 7 days, 1 year, and 2 years. RESULTS From 2003 to 2008, 6437 ischemic stroke patients were discharged home from hospital, and 1126 patients filled a prescription for antihypertensive and lipid-lowering agents within 7 days of discharge. Patients provided with a prescription at discharge were more likely to show adherence at 7 days. Adherence at 1 year remains higher in these patients for antihypertensive (93.8% vs. 87.7%; odds ratio [OR], 2.31; 95% confidence interval [CI], 1.69-3.16), lipid-lowering agents (88% vs. 81.6%; OR, 1.77; 95% CI, 1.36-2.32), or both (85.8% vs. 79.9%; OR, 1.72; 95% CI, 1.32-2.25). Findings are similar at 2 years for antihypertensive (92.2% vs. 87.7%; OR, 1.78; 95% CI, 1.3-2.43), lipid-lowering agents (82.6% vs. 79.0%; OR, 1.31; 95% CI, 1.01-1.69), or both (81.1% vs. 77.0%; OR, 1.4; 95% CI, 1.09-1.82). CONCLUSIONS Provision of a prescription strengthens adherence at 1 week from discharge for both prior and new users of antihypertensive and lipid-lowering drugs. Medication adherence at 1 week after discharge for acute ischemic stroke predicts adherence for secondary preventive therapies at 1 and 2 years.

Stroke Journal What Is Being Published to Advance the Field

Stroke is a monthly peer-reviewed journal that just celebrated its 42nd publication year. Its target audience is broad, including general practitioners, general and vascular neurologists, basic scientists, cardiologists, vascular surgeons, internists, interventional radiologist, neurosurgeons, physiatrists, and stroke rehabilitation experts. Stroke publishes 12 monthly editions per year comprising ≈3500 pages per year, and it is indexed in Biosciences Information Service, Current Awareness in Biological Sciences, Chemical Abstracts, Cumulative Index Nursing and Allied Health Literature, Current Contents, Excerpta Medica database, and MEDLINE. It publishes ≈30 original research articles, 8 brief reports, and 5 other types of articles in each issue, ≈100% of its content related to the field of cerebrovascular diseases. Other neurology journals only publish ≤15% of their content related to cerebrovascular disease.1,2 Peer-reviewed publications are an important component of academic activity, as it constitutes a form of feedback to authors by qualified colleagues with expertise in a specific field and provides readers with up-to-date information. Peer-reviewed publications are also used to maintain standards of quality, evaluate academic performance, and are an essential part of the dissemination of research, describing innovative interventions and discoveries in clinical and basic science.3 Stroke is considered the most important peer-reviewed journal in the area of cerebrovascular disorders, ranking number 7 among 66 journals in the Peripheral Vascular Disease category and number 13 among 185 journals in the Clinical Neurology category (2010 Journal Citation Reports Thomson Reuters, 2011). Limited information is available on what is being published in Stroke . A better understanding of common topics and factors influencing the acceptance rate would not only be informative for Stroke readers, but also be helpful for authors when submitting a new article and for editors when making decisions. Our aims were (1) to provide a comprehensive review of most common topics published in …

Effect of English Proficiency and Research Funding on Acceptance of Submitted Articles to Stroke Journal

Science is a shared and global undertaking that requires cumulative contributions from scientists from all around the world. Peer-reviewed publications, which are an essential part of the dissemination of scientific research, provide information on innovative interventions and discoveries,1 guide funding agency grant-making decisions, constitute a major criterion in academic faculty promotion, affect the receipt of career milestone awards, and can be pivotal in the allocation of public health resources.2,3 As the channels through which peer-reviewed publications become accessible to the scientific world, journals are science’s gatekeepers, wielding tremendous influence on whether various scientific works receive broad readership and recognition. Given that the English language has become the international lingua franca of scientific communication, with most high effect journals being published in English,4,5 authors’ native language may be a barrier to the publication of otherwise scientifically worthy articles, thereby limiting international knowledge exchange among scientists. Indeed, it is conceivable that novel ideas or projects not properly articulated in English may be inadvertently assigned low-priority scores, whereas less innovative, but well-written articles (ie, from countries with high English proficiency) may receive high-priority scores and eventually be published. Another nonscientific issue that may affect an article acceptance could be economic: articles from countries with relatively lower overall research funding may be held to a higher threshold of acceptance, based on a perception of potentially less developed scientific culture and rigor. Worldwide, the journal Stroke is generally regarded as the premier scientific journal covering cerebrovascular disorders. For Stroke , priority scores depend on the experimental design, effect, innovation, and quality of the article, but other factors also influence the acceptance rate as highlighted in a previous report.6 A better understanding of language barriers and economic factors influencing the acceptance rate would be informative for Stroke readers, …