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.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study.

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.

Effect of apixaban on brain infarction and microbleeds: AVERROES-MRI assessment study.

BACKGROUND: Clinical and subclinical (covert) stroke is a cause of cognitive loss and functional impairment. In the AVERROES trial, we performed serial brain magnetic resonance imaging (MRI) scans in a subgroup to explore the effect of apixaban, compared with aspirin, on clinical and covert brain infarction and on microbleeds in patients with atrial fibrillation. METHODS: We performed brain MRI (T1, T2, fluid-attenuated inversion recovery, and T2* gradient echo sequences) in 1,180 at baseline and in 931 participants at follow-up. Mean interval from baseline to follow-up MRI scans was 1.0 year. The primary outcome was a composite of clinical ischemic stroke and covert embolic pattern infarction (defined as infarction >1.5 cm, cortical-based infarction, or new multiterritory infarction). Secondary outcomes included new MRI-detected brain infarcts and microbleeds and change in white matter hyperintensities. RESULTS: Baseline MRI scans revealed brain infarct(s) in 26.2% and microbleed(s) in 10.5%. The rate of the primary outcomes was 2.0% in the apixaban group and 3.3% in the aspirin group (hazard ratio [HR] 0.55; 0.27-1.14) from baseline to follow-up MRI scan (mean duration of follow-up: 1 year). In those who completed baseline and follow-up MRI scans, the rate of new infarction detected on MRI was 2.5% in the apixaban group and 2.2% in the aspirin group (HR 1.09; 0.47-2.52), but new infarcts were smaller in the apixaban group (P = .03). There was no difference in proportion with new microbleeds on follow-up MRI (HR 0.92; 0.53-1.60) between treatment groups. CONCLUSIONS: Apixaban treatment was associated with a nonsignificant trend toward reduction in the composite of clinical ischemic stroke and covert embolic-pattern infarction and did not increase the number of microbleeds in patients with atrial fibrillation compared with aspirin.

Assessment of Dietary Sodium and Potassium in Canadians Using 24-Hour Urinary Collection.

BACKGROUND: Although salt intake derived from data on urinary sodium excretion in free-living populations has been used in public policy, a population study on urinary sodium excretion has not been done in Canada. We assessed dietary sodium and potassium intake using a 24-hour urine collection in a large survey of urban and rural communities from 4 Canadian cities and determined the association of these electrolytes with blood pressure (BP). METHODS: One thousand seven hundred consecutive individuals, aged 37-72 years, attending their annual follow-up visits of the ongoing Prospective and Urban Rural Epidemiology (PURE) study in Vancouver, Hamilton, Ottawa, and Quebec City, Canada, collected a 24-hour urine sample using standardized procedures. RESULTS: Mean sodium excretion was 3325 mg/d and mean potassium excretion was 2935 mg/d. Sodium excretion ranged from 3093 mg/d in Vancouver to 3642 mg/d in Quebec City, after adjusting for covariates. Potassium excretion ranged from 2844 mg/d in Ottawa to 3082 mg/d in Quebec City. Both electrolytes were higher in men than in women and in rural populations than in urban settings (P < 0.001 for all). Sodium excretion was between 3000 and 6000 mg/d in 48.3% of the participants, < 3000 mg/d in 46.7%, and > 6000 mg/d in only 5%. No significant association between sodium or potassium excretion and BP was found. CONCLUSIONS: Sodium consumption in these Canadians is within a range comparable to other Western countries, and intake in most individuals is < 6000 mg/d, with only 5% at higher levels. Within this range, sodium or potassium levels were not associated with BP.

Preventing cardiovascular disease in primary care: role of a national risk factor management program.

BACKGROUND: Heartwatch, a structured risk factor modification program for secondary prevention of cardiovascular (CV) disease (CVD) in primary care, is associated with improvements in CV risk factors in participating patients. However, it is not known whether Heartwatch translates into reductions in clinically important CV events. OBJECTIVE: The aim of the study was to determine the association between participation in Heartwatch and future risk of CV events in patients with CVD. METHODS: The study consisted of a prospective cohort of 1,609 patients with CVD in primary care practices. Of these, 97.5% had data available on Heartwatch participation status, of whom 15.2% were Heartwatch participants. Cox proportional hazards models were used to determine the association between Heartwatch participation and risk of the CV composite (CV death, nonfatal myocardial infarction, heart failure, and nonfatal stroke). All-cause mortality and CV mortality were secondary outcome measures. RESULTS: During follow-up, the CV composite occurred in 208 patients (13.6%). Of Heartwatch participants, 8.4% experienced the CV composite compared with 14.5% of nonparticipants (P = .003). Participation in Heartwatch was associated with a significantly reduced risk of the CV composite (hazard ratio [HR] 0.52, 95% CI, 0.31-0.87), CV mortality (HR 0.31, 95% CI, 0.11-0.89), and all-cause mortality (HR 0.32, 95% CI, 0.15-0.68). Heartwatch participation was also associated with greater reductions in mean systolic blood pressure (P = .047), mean diastolic blood pressure (P < .001), and greater use of secondary preventative therapies for CVD, such as lipid-lowering agents (P < .001), ß-blockers (P < .001), and angiotensin-converting enzyme inhibitors (P < .001). CONCLUSION: Heartwatch is associated with a reduced risk of major vascular events and improved risk factor modification, supporting its potential as a nationwide program for secondary prevention of CVD.

Distributed Drug Discovery, Part 2: global rehearsal of alkylating agents for the synthesis of resin-bound unnatural amino acids and virtual D(3) catalog construction.

Distributed Drug Discovery (D(3)) proposes solving large drug discovery problems by breaking them into smaller units for processing at multiple sites. A key component of the synthetic and computational stages of D(3) is the global rehearsal of prospective reagents and their subsequent use in the creation of virtual catalogs of molecules accessible by simple, inexpensive combinatorial chemistry. The first section of this article documents the feasibility of the synthetic component of Distributed Drug Discovery. Twenty-four alkylating agents were rehearsed in the United States, Poland, Russia, and Spain, for their utility in the synthesis of resin-bound unnatural amino acids 1, key intermediates in many combinatorial chemistry procedures. This global reagent rehearsal, coupled to virtual library generation, increases the likelihood that any member of that virtual library can be made. It facilitates the realistic integration of worldwide virtual D(3) catalog computational analysis with synthesis. The second part of this article describes the creation of the first virtual D(3) catalog. It reports the enumeration of 24,416 acylated unnatural amino acids 5, assembled from lists of either rehearsed or well-precedented alkylating and acylating reagents, and describes how the resulting catalog can be freely accessed, searched, and downloaded by the scientific community.