Yongchai Nilanont

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study

BACKGROUND Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Efficacy and safety of non-immersive virtual reality exercising in stroke rehabilitation (EVREST): a randomised, multicentre, single-blind, controlled trial

BACKGROUND Non-immersive virtual reality is an emerging strategy to enhance motor performance for stroke rehabilitation. There has been rapid adoption of non-immersive virtual reality as a rehabilitation strategy despite the limited evidence about its safety and effectiveness. Our aim was to compare the safety and efficacy of virtual reality with recreational therapy on motor recovery in patients after an acute ischaemic stroke. METHODS In this randomised, controlled, single-blind, parallel-group trial we enrolled adults (aged 18-85 years) who had a first-ever ischaemic stroke and a motor deficit of the upper extremity score of 3 or more (measured with the Chedoke-McMaster scale) within 3 months of randomisation from 14 in-patient stroke rehabilitation units from four countries (Canada [11], Argentina [1], Peru [1], and Thailand [1]). Participants were randomly allocated (1:1) by a computer-generated assignment at enrolment to receive a programme of structured, task-oriented, upper extremity sessions (ten sessions, 60 min each) of either non-immersive virtual reality using the Nintendo Wii gaming system (VRWii) or simple recreational activities (playing cards, bingo, Jenga, or ball game) as add-on therapies to conventional rehabilitation over a 2 week period. All investigators assessing outcomes were masked to treatment assignment. The primary outcome was upper extremity motor performance measured by total time to complete the Wolf Motor Function Test (WMFT) at the end of the 2 week intervention period, analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NTC01406912. FINDINGS The study was done between May 12, 2012, and Oct 1, 2015. We randomly assigned 141 patients: 71 received VRWii therapy and 70 received recreational activity. 121 (86%) patients (59 in the VRWii group and 62 in the recreational activity group) completed the final assessment and were included in the primary analysis. Each group improved WMFT performance time relative to baseline (decrease in median time from 43·7 s [IQR 26·1-68·0] to 29·7 s [21·4-45·2], 32·0% reduction for VRWii vs 38·0 s [IQR 28·0-64·1] to 27·1 s [21·2-45·5], 28·7% reduction for recreational activity). Mean time of conventional rehabilitation during the trial was similar between groups (VRWii, 373 min [SD 322] vs recreational activity, 397 min [345]; p=0·70) as was the total duration of study intervention (VRWii, 528 min [SD 155] vs recreational activity, 541 min [142]; p=0·60). Multivariable analysis adjusted for baseline WMFT score, age, sex, baseline Chedoke-McMaster, and stroke severity revealed no significant difference between groups in the primary outcome (adjusted mean estimate of difference in WMFT: 4·1 s, 95% CI -14·4 to 22·6). There were three serious adverse events during the trial, all deemed to be unrelated to the interventions (seizure after discharge and intracerebral haemorrhage in the recreational activity group and heart attack in the VRWii group). Overall incidences of adverse events and serious adverse events were similar between treatment groups. INTERPRETATION In patients who had a stroke within the 3 months before enrolment and had mild-to-moderate upper extremity motor impairment, non-immersive virtual reality as an add-on therapy to conventional rehabilitation was not superior to a recreational activity intervention in improving motor function, as measured by WMFT. Our study suggests that the type of task used in motor rehabilitation post-stroke might be less relevant, as long as it is intensive enough and task-specific. Simple, low-cost, and widely available recreational activities might be as effective as innovative non-immersive virtual reality technologies. FUNDING Heart and Stroke Foundation of Canada and Ontario Ministry of Health.

The Canadian Neurological Scale and the NIHSS: Development and Validation of a Simple Conversion Model

Background: The Canadian Neurological Scale (CNS) and the National Institutes of Health Stroke Scale (NIHSS) are among the most reliable stroke severity assessment scales. The CNS requires less extensive neurological evaluation and is quicker and simpler to administer. Objective: Our aim was to develop and validate a simple conversion model from the CNS to the NIHSS. Methods: A conversion model was developed using data from a consecutive series of acute-stroke patients who were scored using both scales. The model was then validated in an external dataset in which all patients were prospectively assessed for stroke severity using both scales by different observers which consisted of neurology residents or stroke fellows. Results: In all, 168 patients were included in the model development, with a median age of 73 years (20–94). Men constituted 51.8%. The median NIHSS score was 6 (0–31). The median CNS score was 8.5 (1.5–11.5). The relationship between CNS and NIHSS could be expressed as the formula: NIHSS = 23 – 2 × CNS. A cohort of 350 acute-stroke patients with similar characteristics was used for model validation. There was a highly significant positive correlation between the observed and predicted NIHSS score (r = 0.87, p < 0.001). The predicted NIHSS score was on average 0.61 higher than the observed NIHSS score (95% CI = 0.31–0.91). Conclusions: The CNS can be reliably converted to the NIHSS using a simple conversion formula: NIHSS = 23 – 2 × CNS. This finding may have a practical impact by permitting reliable comparisons with NIHSS-based evaluations and simplifying the routine assessment of acute-stroke patients in more diverse settings.

Neglecting the Difference. Does Right or Left Matter in Stroke Outcome After Thrombolysis

Background and Purpose— Patients with right hemispheric strokes (RHSs) present later to an emergency department, have a lower chance to receive intravenous recombinant tissue plasminogen activator (IV rt-PA), and have worse clinical outcomes than do patients with left hemispheric strokes (LHSs). We analyzed outcomes after IV rt-PA with respect to the side of the affected hemisphere. Methods— A prospective cohort of acute stroke patients was treated with IV rt-PA at the London Health Sciences Centre (December 1998 to March 2003). Differences between patients with RHS and LHS were identified by univariate analysis. Logistic-regression analysis was used to determine a subset of variables independently associated with major neurological improvement at 24 hours and good outcome at 3 months after treatment. Results— Of 219 stroke patients who received IV rt-PA, 165 had hemispheric strokes (68 RHSs and 97 LHSs). Patients with RHSs were less hypertensive (P=0.001) and had lower pretreatment National Institutes of Health Stroke Scale (NIHSS) scores (P=0.005). LHS (odds ratio [OR], 2.29; 95% CI, 1.14 to 4.59; P=0.019), age (OR, 0.96; 95% CI, 0.93 to 0.99; P=0.012), and pretreatment NIHSS (OR, 0.83; 95% CI, 0.78 to 0.89; P<0.0001) were independent predictors of 3-month outcome. Female sex (OR, 3; 95% CI, 1.53 to 5.90; P=0.001) and LHS (OR, 2.07; 95% CI, 1.05 to 4.08; P=0.03) were independent predictors of major neurological improvement at 24 hours after IV rt-PA. Conclusions— Despite higher pretreatment NIHSS, patients with LHSs have a 2-fold increased chance of a good outcome 3 months after rt-PA treatment compared with patients with RHSs. This gain can be clinically detected at 24 hours after treatment. These results need to be coupled with neuroimaging and hemodynamic characteristics known to influence stroke outcome.

Quality of acute ischemic stroke care in Thailand: a prospective multicenter countrywide cohort study.

BACKGROUND Data concerning quality of acute stroke care and outcome are scarce in developing countries. OBJECTIVE This study aimed to evaluate quality of acute stroke care and stroke outcomes in Thailand. METHODS We performed a multicenter countrywide prospective cohort study. Consecutive patients with an acute ischemic stroke admitted to the participating institutions between June 2008 and November 2010 were included. Baseline characteristics, process measures including thrombolysis use, acute stroke unit admission, initiation of aspirin within 48 hours, and antithrombotic and/or anticoagulation medication at discharge were recorded. Main outcome measures were death and disability at discharge as well as in-hospital complications. RESULTS A total of 1222 patients were included with a mean (±SD) age of 65.0 ± 13 years, and 55.0% were men. Median National Institutes of Health Stroke Scale score was 6.5. Patients were given aspirin within 48 hours, admitted to acute stroke unit, and given thrombolytic therapy in 71.1%, 24.6%, and 3.8%, respectively. Good recovery at discharge (modified Rankin scale score 0-1) was found in 26.1%, and 3.2% of patients died during hospitalization. The median length of stay was 4 days. Factors predicting poor outcome (modified Rankin scale score 5-6) at discharge included: age (by 10-year increments: adjusted odds ratio [OR] 1.23; 95% confidence interval [CI], 1.06-1.43), female sex (adjusted OR 1.52; 95% CI, 1.05-2.19), initial National Institutes of Health Stroke Scale score (adjusted OR 1.35; 95% CI, 1.27-1.43), and in-hospital complications (adjusted OR 3.16; 95% CI, 1.58-6.35). CONCLUSIONS Limited access to acute ischemic stroke care interventions were observed in many domains especially thrombolysis and stroke unit admission. These findings emphasize an urgent need for strategies to improve standard acute stroke care among developing countries.

Pulmonary Embolism in Ischemic Stroke: Clinical Presentation, Risk Factors, and Outcome

Background Limited information is available on the frequency of pulmonary embolism (PE) in patients with an acute ischemic stroke (AIS). We evaluated clinical characteristics, predisposing factors, and outcomes in AIS patients with PE. Methods and Results We included all AIS patients admitted to participating institutions in the Registry of the Canadian Stroke Network. Clinically PE was documented by a physician and confirmed by computed tomography pulmonary angiography within 30 days of the stroke case index. The primary outcome was death or disability at discharge. Secondary outcomes included disposition, length of hospital stay, mortality at 3 months and 1 year. Among 11 287 patients with AIS, PE was found in 89 (0.78%) patients. History of cancer, deep vein thrombosis (DVT)/PE, and DVT during the hospitalization were associated with PE. PE was associated with higher risk of death at 30 days (25.8% versus 13.6%; P<0.001), at 1 year (47.2% versus 24.6%; P<0.001), and disability at discharge (85.4% versus 63.6%; P<0.001). Mean length of stay was longer in stroke patients with PE (36 versus 16 days; P=0.001). After adjusting for age, sex, and stroke severity, PE remained associated with lower survival at 30 days and 1 year, and death or disability at discharge (OR 3.02; 95% CI 1.56 to 5.83). Conclusions In this large cohort study, PE occurred in nearly 1% of AIS patients. PE was more common in patients with severe stroke, history of cancer, previous DVT/PE or acute DVT and associated with lower short‐ and long‐term survival, greater disability, and longer length of stay.