Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

Language discordance as a marker of disparities in cerebrovascular risk and stroke outcomes: A multi-center Canadian study.

Background: Differences in ischemic stroke outcomes occur in those with limited English proficiency. These health disparities might arise when a patient's spoken language is discordant from the primary language utilized by the health system. Language concordance is an understudied concept. We examined whether language concordance is associated with differences in vascular risk or post-stroke functional outcomes, depression, obstructive sleep apnea and cognitive impairment. Methods: This was a multi-center observational cross-sectional cohort study. Patients with ischemic stroke/transient ischemic attack (TIA) were consecutively recruited across eight regional stroke centers in Ontario, Canada (2012 - 2018). Participants were language concordant (LC) if they spoke English as their native language, ESL if they used English as a second language, or language discordant (LD) if non-English speaking and requiring translation. Results: 8156 screened patients. 6,556 met inclusion criteria: 5067 LC, 1207 ESL and 282 LD. Compared to LC patients: (i) ESL had increased odds of diabetes (OR = 1.28, p = 0.002), dyslipidemia (OR = 1.20, p = 0.007), and hypertension (OR = 1.37, p<0.001) (ii) LD speaking patients had an increased odds of having dyslipidemia (OR = 1.35, p = 0.034), hypertension (OR = 1.37, p<0.001), and worse functional outcome (OR = 1.66, p<0.0001). ESL (OR = 1.88, p<0.0001) and LD (OR = 1.71, p<0.0001) patients were more likely to have lower cognitive scores. No associations were noted with obstructive sleep apnea (OSA) or depression. Conclusions: Measuring language concordance in stroke/TIA reveals differences in neurovascular risk and functional outcome among patients with limited proficiency in the primary language of their health system. Lower cognitive scores must be interpreted with caution as they may be influenced by translation and/or greater vascular risk. Language concordance is a simple, readily available marker to identify those at risk of worse functional outcome. Stroke systems and practitioners must now study why these differences exist and devise adaptive care models, treatments and education strategies to mitigate barriers influenced by language discordance.

Assessing care-related regret among nurses specialized in multiple sclerosis: A psychometric analysis of a new assessment battery.

Experiences of regret associated with caring for patients with multiple sclerosis (MS) can affect medical decisions. A non-interventional study was conducted to assess the dimensionality and item characteristics of a battery including the Regret Intensity Scale (RIS-10) and 15 items evaluating common situations experienced by nurses in MS care. A total of 97 nurses were included. The RIS-10 showed good internal reliability and a unidimensional structure according to Mokken analysis. All-item homogeneity coefficients exceeded 0.30, whereas scalability for the overall RIS-10 was 0.66, indicating a strong scale. This battery showed adequate psychometric properties to evaluate regret among MS nurses.

Therapeutic Decisions in Atrial Fibrillation for Stroke Prevention: The Role of Aversion to Ambiguity and Physicians' Risk Preferences.

BACKGROUND: Knowledge-to-action gaps influence therapeutic decisions in atrial fibrillation (AF). Physician-related factors are common, but the least studied. We evaluated the prevalence and determinants of physician-related factors and knowledge-to-action gaps among physicians involved in the management of AF patients. DESIGN: In this cross-sectional study, participants from 6 South American countries recruited during an educational program answered questions regarding 16 case scenarios of patients with AF and completed experiments assessing 3 outcome measures: therapeutic inertia, herding, and errors in risk stratification knowledge translated into action (ERSKTA) based on commonly used stratification tools (Congestive heart failure, Hypertension, Age ≥75 years (double), Diabetes mellitus, previous Stroke/transient ischemic attack/thromboembolism (double), Vascular disease, Age 65-74 years, and female gender (score of 0 for males and 1 for female) (CHA2DS2-VASc) and Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, and previous Stroke/transient ischemic attack (double) (CHADS2)). Logistic regression analysis was conducted to determine factors associated with the outcomes. RESULTS: Overall, 149 physicians were invited to participate, of which 88 (59.1%) completed the online assessment tool. Cardiology was the most frequent specialty (69.3%). Therapeutic inertia was present in 53 participants (60.2%), herding in 66 (75.0%), and ERSKTA in 46 (52.3%). Therapeutic inertia was inversely associated with willingness to take financial risks (odds ratio [OR] .72, 95% confidence interval [CI] .59-.89 per point in the financial risk propensity score), herding was associated with aversion to ambiguity in the medical domain (OR 5.35, 95% CI 1.40-20.46), and ERSKTA was associated with the willingness to take risks (OR 1.70, 95% CI 1.15-2.50, per point in score). CONCLUSIONS: Among physicians involved in stroke prevention in AF, individual risk preferences and aversion to ambiguity lead to therapeutic inertia, herding, and errors in risk stratification and subsequent use of oral anticoagulants. Educational interventions, including formal training in risk management and decision-making are needed.

Countries with women inequalities have higher stroke mortality.

Background Stroke outcomes can differ by women's legal or socioeconomic status. Aim We investigated whether differences in women's rights or gender inequalities were associated with stroke mortality at the country-level. Methods We used age-standardized stroke mortality data from 2008 obtained from the World Health Organization. We compared female-to-male stroke mortality ratio and stroke mortality rates in women and men between countries according to 50 indices of women's rights from Women, Business and the Law 2016 and Gender Inequality Index from the Human Development Report by the United Nations Development Programme. We also compared stroke mortality rate and income at the country-level. Results In our study, 176 countries with data available on stroke mortality rate in 2008 and indices of women's rights were included. There were 46 (26.1%) countries where stroke mortality in women was higher than stroke mortality in men. Among them, 29 (63%) countries were located in Sub-Saharan African region. After adjusting by country income level, higher female-to-male stroke mortality ratio was associated with 14 indices of women's rights, including differences in getting a job or opening a bank account, existence of domestic violence legislation, and inequalities in ownership right to property. Moreover, there was a higher female-to-male stroke mortality ratio among countries with higher Gender Inequality Index (r = 0.397, p < 0.001). Gender Inequality Index was more likely to be associated with stroke mortality rate in women than that in men (p < 0.001). Conclusions Our study suggested that the gender inequality status is associated with women's stroke outcomes.

Incidence and management of seizures after ischemic stroke: Systematic review and meta-analysis.

OBJECTIVE: We conducted a meta-analysis of the incidence of early and late seizures following ischemic stroke as well as a systematic review of their pharmacologic treatment. METHODS: Observational studies that reported incidence of seizures following ischemic stroke and those that reported treatment response to any particular antiepileptic drugs (AEDs) were included. Risk of bias was assessed by predefined study characteristics. Random effects meta-analysis was conducted for all studies where data were available for the incidence of early and late stroke-related seizures. Heterogeneity was measured with I2 statistic and sensitivity analyses were performed using prespecified variables. A qualitative synthesis of studies reporting use of AEDs for stroke-related seizures was performed. RESULTS: Forty-one studies from 10,554 articles were identified; 35 studies reported incidence of stroke-related seizures and 6 studies reported effects of specific AEDs. Most studies were of low to moderate quality. Rate of early seizures was 3.3% (95% confidence interval 2.8%-3.9%, I2 = 92.8%), while the incidence of late seizures or epilepsy was 18 per 1,000 person-years (95% confidence interval 1.5-2.2, I2 = 94.1%). The high degree of heterogeneity could not be explained from the sensitivity analyses. For management of stroke-related seizures, no single AED was found to be more effective over others, though newer AEDs were associated with fewer side effects. CONCLUSIONS: The burden of stroke-related seizures and epilepsy due to ischemic stroke is substantial. Further studies are required to determine risk factors for epilepsy following ischemic stroke and optimal secondary prevention.

Does national expenditure on research and development influence stroke outcomes?

Background Expenditure on research and development is a macroeconomic indicator representative of national investment. International organizations use this indicator to compare international research and development activities. Aim We investigated whether differences in expenditures on research and development at the country level may influence the incidence of stroke and stroke mortality. Methods We compared stroke metrics with absolute amount of gross domestic expenditure on R&D (GERD) per-capita adjusted for purchasing power parity (aGERD) and relative amount of GERD as percent of gross domestic product (rGERD). Sources included official data from the UNESCO, the World Health Organization, the World Bank, and population-based studies. We used correlation analysis and multivariable linear regression modeling. Results Overall, data on stroke mortality rate and GERD were available from 66 countries for two periods (2002 and 2008). Age-standardized stroke mortality rate was associated with aGERD (r = -0.708 in 2002 and r = -0.730 in 2008) or rGERD (r = -0.545 in 2002 and r = -0.657 in 2008) (all p < 0.001). Multivariable analysis showed a lower aGERD and rGERD were independently and inversely associated with higher stroke mortality (all p < 0.05). The estimated prevalence of hypertension, diabetes, or obesity was higher in countries with lower aGERD. The analysis of 27 population-based studies showed consistent inverse associations between aGERD or rGERD and incident risk of stroke and 30-day case fatality. Conclusions There is higher stroke mortality among countries with lower expenditures in research and development. While this study does not prove causality, it suggests a potential area to focus efforts to improve global stroke outcomes.

Mechanical thrombectomy in patients with acute ischemic stroke: a cost-utility analysis.

BACKGROUND: The beneficial effects of endovascular treatment with new-generation mechanical thrombectomy devices compared with intravenous thrombolysis alone to treat acute large-artery ischemic stroke have been shown in randomized controlled trials (RCTs). This study aimed to estimate the cost utility of mechanical thrombectomy compared with the established standard of care. METHODS: We developed a Markov decision process analytic model to assess the cost-effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis versus treatment with intravenous thrombolysis alone from the public payer perspective in Canada. We conducted comprehensive literature searches to populate model inputs. We estimated the efficacy of mechanical thrombectomy plus intravenous thrombolysis from a meta-analysis of 5 RCTs, and we used data from the Oxford Vascular Study to model long-term clinical outcomes. We calculated incremental cost-effectiveness ratios (ICER) using a 5-year time horizon. RESULTS: The base case analysis showed the cost and effectiveness of treatment with mechanical thrombectomy plus intravenous thrombolysis to be $126 939 and 1.484 quality-adjusted life-years (QALYs), respectively, and the cost and effectiveness of treatment with intravenous thrombolysis alone to be $124 419 and 1.273 QALYs, respectively. The mechanical thrombectomy plus intravenous thrombolysis strategy was associated with an ICER of $11 990 per QALY gained. Probabilistic sensitivity analysis showed that the probability of treatment with mechanical thrombectomy plus intravenous thrombolysis being cost-effective was 57.5%, 89.7% and 99.6% at thresholds of $20 000, $50 000 and $100 000 per QALY gained, respectively. The main factors influencing the ICER were time horizon, extra cost of mechanical thrombectomy treatment and age of the patient. INTERPRETATION: Mechanical thrombectomy as an adjunct therapy to intravenous thrombolysis is cost-effective compared with treatment with intravenous thrombolysis alone for patients with acute large-artery ischemic stroke.

Disparities in surgery among patients with intractable epilepsy in a universal health system.

OBJECTIVE: To assess the use of epilepsy surgery in patients with medically intractable epilepsy in a publicly funded universal health care system. METHODS: We performed a population-based retrospective cohort study using linked health care databases for Ontario, Canada, between 2001 and 2010. We identified all patients with medically intractable epilepsy, defined as those with seizures that did not respond to at least 2 adequate trials of seizure medications. We assessed the proportion of patients who had epilepsy surgery within the following 2 years. We further identified the characteristics associated with epilepsy surgery. RESULTS: A total of 10,661 patients were identified with medically intractable epilepsy (mean age 47 years, 51% male); most (74%) did not have other comorbidities. Within 2 years of being defined as medically intractable, only 124 patients (1.2%) underwent epilepsy surgery. Death occurred in 12% of those with medically intractable epilepsy. Those who underwent the procedure were younger and had fewer comorbidities compared to those who did not. CONCLUSION: In our setting of publicly funded universal health care, more than 10% of patients died within 2 years of developing medically intractable epilepsy. Epilepsy surgery may be an effective treatment for some patients; however, fewer than 2% of patients who may have benefited from epilepsy surgery received it.

The iScore predicts total healthcare costs early after hospitalization for an acute ischemic stroke.

BACKGROUND: The ischemic Stroke risk score is a validated prognostic score which can be used by clinicians to estimate patient outcomes after the occurrence of an acute ischemic stroke. AIM: In this study, we examined the association between the ischemic Stroke risk score and patients' 30-day, one-year, and two-year healthcare costs from the perspective of a third party healthcare payer. METHODS: Patients who had an acute ischemic stroke were identified from the Registry of Canadian Stroke Network. The 30-day ischemic Stroke risk score prognostic score was determined for each patient. Direct healthcare costs at each time point were determined using administrative databases in the province of Ontario. Unadjusted mean and the impact of a 10-point increase ischemic Stroke risk score and a patient's risk of death or disability on total cost were determined. RESULTS: There were 12,686 patients eligible for the study. Total unadjusted mean costs were greatest among patients at high risk. When adjusting for patient characteristics, a 10-point increase in the ischemic Stroke risk score was associated with 8%, 7%, and 4% increase in total costs at 30 days, one-year, and two-years. The same increase was found to impact patients at low, medium, and high risk differently. When adjusting for patient characteristics, patients in the high-risk group had the highest total costs at 30 days, while patients at medium risk had the highest costs at both one and two-years. CONCLUSIONS: The ischemic Stroke risk score can be useful as a predictor of healthcare utilization and costs early after hospitalization for an acute ischemic stroke.

Cognitive, on-road, and simulator-based driving assessment after stroke.

Driving is a complex activity that requires intact cognitive, behavioral, and motor function. Stroke is one of the most prevalent neurologic impairments and can affect all of these functions. However, diagnosis of stroke is not a definitive indicator of driving impairment. Determining fitness to drive after stroke is a very complex process and is typically based on cognitive assessments, on-road performance, simulator-based assessment, or a combination of the three. The aim of this review was to provide (1) a systematic review of the literature on cognitive, on-road, and simulator assessment after stroke, and (2) address the existing limitations and inconsistencies in stroke and driving research. Our results indicated that of 1413 total stroke patients, 748 definitively passed and 367 definitely failed an on-road assessment, with minimal information provided about clinical presentation. In addition, although the Stroke Driver Screening Assessment, the Useful Field of View Test, and the Rey-O Complex Figure test may have some utility in predicting driving performance, most cognitive measures have been inconsistently and minimally explored. Several limitations were observed across studies such as procedural inconsistencies, including outcome variables used (eg, driving cessation and pass/fail classification) and the heterogeneity of patient samples (eg, time since stroke and stroke location). Due, in part, to the larger variability in results of cognitive, on-road, and simulator-based assessment, there is no consensus regarding a valid and reliable driving assessment for physicians. Future studies should assess poststroke driving fitness by differentiating different stages, severities, and locations of stroke.

The CLOQS trial protocol: a cluster-randomized trial evaluating a simple, low-cost intervention to reduce treatment times in acute stroke.

RATIONALE: In acute stroke, time is brain: faster tissue plasminogen activator treatment improves patient outcomes. Published guidelines for door-to-scanner time are <25 minutes, and for door-to-needle time <60 minutes. These benchmarks are rarely met. Paradoxically, the earlier a stroke patient arrives to hospital, the longer treatment takes. There is an urgent need to shift focus away from the 4.5 hour time window, towards treatment times <60 minutes. AIMS: The objective of the Countdown Lights to Optimize Quality in acute Stroke (CLOQS) trial is to determine whether a simple, low-cost organizational behavior intervention, a large, red stopwatch timer attached to the stretcher upon arrival, will decrease door-to-scanner and door-to-needle treatment times for tissue plasminogen activator-treated patients. DESIGN: A multicenter, time-clustered randomized control trial. The stopwatch timers will be used in Emergency Departments for all acute stroke patients across the University of Toronto Stroke Program. The order of intervention (ON) and control (OFF) blocks will be randomly assigned in a 1:1 ratio over an 18 month period. Blocks will be weighted in a 2:1 ratio of ON/OFF using a permuted block design (ON blocks last two weeks; OFF blocks last one week). STUDY OUTCOMES: The primary end-point is percentage of patients achieving best-practice guidelines (door-to-needle treatment time <60 minutes). Secondary end-points are median time intervals for 1) door-to-scanner and 2) door-to-needle times during ON versus OFF blocks. Tertiary end-points are in-hospital mortality and time series analysis to determine change in treatment times from prior to study onset through study completion.

Confusion assessment method: a systematic review and meta-analysis of diagnostic accuracy.

BACKGROUND: Delirium is common in the early stages of hospitalization for a variety of acute and chronic diseases. OBJECTIVES: To evaluate the diagnostic accuracy of two delirium screening tools, the Confusion Assessment Method (CAM) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU). METHODS: We searched MEDLINE, EMBASE, and PsychInfo for relevant articles published in English up to March 2013. We compared two screening tools to Diagnostic and Statistical Manual of Mental Disorders IV criteria. Two reviewers independently assessed studies to determine their eligibility, validity, and quality. Sensitivity and specificity were calculated using a bivariate model. RESULTS: Twenty-two studies (n = 2,442 patients) met the inclusion criteria. All studies demonstrated that these two scales can be administered within ten minutes, by trained clinical or research staff. The pooled sensitivities and specificity for CAM were 82% (95% confidence interval [CI]: 69%-91%) and 99% (95% CI: 87%-100%), and 81% (95% CI: 57%-93%) and 98% (95% CI: 86%-100%) for CAM-ICU, respectively. CONCLUSION: Both CAM and CAM-ICU are validated instruments for the diagnosis of delirium in a variety of medical settings. However, CAM and CAM-ICU both present higher specificity than sensitivity. Therefore, the use of these tools should not replace clinical judgment.

Multiple sclerosis disease-modifying therapy prescribing patterns in Ontario.

BACKGROUND: Differences in Multiple sclerosis (MS) disease-modifying therapy (DMT) prescribing patterns between different groups of neurologists have not been explored. OBJECTIVE: To examine concentrations of prescribing patterns and to assess if MS-specialists use a broader range of DMTs relative to general neurologists. METHODS: We conducted a cross-sectional study using administrative claims databases in Ontario, Canada to link neurologists to 2009 DMT prescription data. MS specialization was defined using both practice location and prescription patterns. Lorenz curves and Gini coefficients were constructed to examine prescribing patterns, separating neurologist characteristics dichotomously and separating Avonex from the other standard DMTs (Betaseron, Rebif and Copaxone). Gini coefficient 95% confidence intervals (CIs) were derived using jack-knife statistical techniques. RESULTS: Prescriptions were highly concentrated with 12% of Ontario neurologists prescribing 80% of DMTs. There was a trend towards Avonex being more commonly prescribed relative to the other DMTs. When MS specialization was defined by DMT prescribing, high-volume prescribing neurologists showed a broader range of DMT prescribing (Gini 0.38-0.44) in comparison to low-volume prescribers (Gini 0.57-0.66). CONCLUSIONS: The majority of DMTs are prescribed by a small subset of neurologists. High-volume prescribing MS-specialists show more variability in DMT use while low-volume prescribers tend to individually focus on a narrower range of DMTs.

Genetic testing in combination with preventive donepezil treatment for patients with amnestic mild cognitive impairment: an exploratory economic evaluation of personalized medicine.

OBJECTIVE: To evaluate the cost effectiveness of genetic screening for the apolipoprotein (APOE) ε4 allele in combination with preventive donepezil treatment in comparison with the standard of care for amnestic mild cognitive impairment (AMCI) patients in Canada. METHODS: We performed a cost-effectiveness analysis using a Markov model with a societal perspective and a time horizon of 30 years. For each strategy, we calculated quality-adjusted life-years (QALYs), using utilities from the literature. Costs were also based on the literature and, when appropriate, Ontario sources. One-way and probabilistic sensitivity analyses were performed. Expected value of perfect information (EVPI) analysis was conducted to explore the value of future research. RESULTS: The base case results in our exploratory study suggest that the combination of genetic testing and preventive donepezil treatment resulted in a gain of 0.027 QALYs and an incremental cost of $1,015 (in 2009 Canadian dollars [Can$]), compared with the standard of care. The incremental cost-effectiveness ratio (ICER) for the base case was Can$38,016 per QALY. The ICER was sensitive to the effectiveness of donepezil in slowing the rate of progression to Alzheimer's disease (AD), utility in AMCI patients, and AD and donepezil treatment costs. EVPI analysis showed that additional information on these parameters would be of value. CONCLUSION: Using presently available clinical evidence, this exploratory study illustrates that genetic testing combined with preventive donepezil treatment for AMCI patients may be economically attractive. Since our results were based on a secondary post hoc analysis, our study alone is insufficient to warrant recommending APOE genotyping in AMCI patients. Future research on the effectiveness of preventive donepezil as a targeted therapy is recommended.

Influence of socioeconomic status on distance traveled and care after stroke.

BACKGROUND AND PURPOSE: Vital to maintaining an efficient delivery of services is an understanding of patient travel patterns during an acute ischemic stroke. Socioeconomic status may influence access to stroke care, including transportation and admission to different facility types. METHODS: We analyzed all acute ischemic stroke admissions between 2003 and 2007 through the Discharge Abstract Database, a national database containing patient-level sociodemographic, diagnostic, procedural, and administrative information across Canada. Socioeconomic status was defined in neighborhood quintiles according to Statistics Canada. Distances between patients and facilities were derived from postal codes. A principal diagnosis of ischemic stroke was identified using the International Classification of Diseases (versions 9 and 10). Analysis of variance and regression analyses were performed with adjustment for demographic characteristics. RESULTS: Admitted to acute care institutions were 243 410 patients with ischemic stroke. Mean patient age was 72.8 and 49.5% were male; 44.2% traveled beyond their closest center, amounting to an average 7.2 km additional distance traveled. Socioeconomic status quintile had minimal effect on travel patterns, with the lowest socioeconomic status accessing the closest center most frequently (odds ratio, 1.19; 95% confidence interval [CI], 1.13-1.16). Increased utilization of the closest hospital occurred with academic (odds ratio, 6.90; 95% CI, 6.69-7.11) or high-volume (odds ratio, 1.93; 95% CI, 1.88-1.98) facilities. Older patients (ß=0.28; 95% CI, 0.27-0.28), expert destination facility (ß=0.13; 95% CI, 0.12-0.14), and ambulance use increased travel beyond the closest center. CONCLUSIONS: Patients tend to choose care facilities based on hospital expertise; investment promoting improved regional facilities may be of greatest benefit to patients. Socioeconomic status has little bearing on travel patterns associated with stroke in Canada. These findings may assist in allocating funding to centers and improving patient care.