Ronald S. MacWalter

The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

Objective To determine whether aspirin and antioxidant therapy, combined or alone, are more effective than placebo in reducing the development of cardiovascular events in patients with diabetes mellitus and asymptomatic peripheral arterial disease. Design Multicentre, randomised, double blind, 2×2 factorial, placebo controlled trial. Setting 16 hospital centres in Scotland, supported by 188 primary care groups. Participants 1276 adults aged 40 or more with type 1 or type 2 diabetes and an ankle brachial pressure index of 0.99 or less but no symptomatic cardiovascular disease. Interventions Daily, 100 mg aspirin tablet plus antioxidant capsule (n=320), aspirin tablet plus placebo capsule (n=318), placebo tablet plus antioxidant capsule (n=320), or placebo tablet plus placebo capsule (n=318). Main outcome measures Two hierarchical composite primary end points of death from coronary heart disease or stroke, non-fatal myocardial infarction or stroke, or amputation above the ankle for critical limb ischaemia; and death from coronary heart disease or stroke. Results No evidence was found of any interaction between aspirin and antioxidant. Overall, 116 of 638 primary events occurred in the aspirin groups compared with 117 of 638 in the no aspirin groups (18.2% v 18.3%): hazard ratio 0.98 (95% confidence interval 0.76 to 1.26). Forty three deaths from coronary heart disease or stroke occurred in the aspirin groups compared with 35 in the no aspirin groups (6.7% v 5.5%): 1.23 (0.79 to 1.93). Among the antioxidant groups 117 of 640 (18.3%) primary events occurred compared with 116 of 636 (18.2%) in the no antioxidant groups (1.03, 0.79 to 1.33). Forty two (6.6%) deaths from coronary heart disease or stroke occurred in the antioxidant groups compared with 36 (5.7%) in the no antioxidant groups (1.21, 0.78 to 1.89). Conclusion This trial does not provide evidence to support the use of aspirin or antioxidants in primary prevention of cardiovascular events and mortality in the population with diabetes studied. Trial registration Current Controlled Trials ISRCTN53295293.

Mental practice with motor imagery in stroke recovery: randomized controlled trial of efficacy

This randomized controlled trial evaluated the therapeutic benefit of mental practice with motor imagery in stroke patients with persistent upper limb motor weakness. There is evidence to suggest that mental rehearsal of movement can produce effects normally attributed to practising the actual movements. Imagining hand movements could stimulate restitution and redistribution of brain activity, which accompanies recovery of hand function, thus resulting in a reduced motor deficit. Current efficacy evidence for mental practice with motor imagery in stroke is insufficient due to methodological limitations. This randomized controlled sequential cohort study included 121 stroke patients with a residual upper limb weakness within 6 months following stroke (on average <3 months post-stroke). Randomization was performed using an automated statistical minimizing procedure. The primary outcome measure was a blinded rating on the Action Research Arm test. The study analysed the outcome of 39 patients involved in 4 weeks of mental rehearsal of upper limb movements during 45-min supervised sessions three times a week and structured independent sessions twice a week, compared to 31 patients who performed equally intensive non-motor mental rehearsal, and 32 patients receiving normal care without additional training. No differences between the treatment groups were found at baseline or outcome on the Action Research Arm Test (ANCOVA statistical P = 0.77, and effect size partial η2 = 0.005) or any of the secondary outcome measures. Results suggest that mental practice with motor imagery does not enhance motor recovery in patients early post-stroke. In light of the evidence, it remains to be seen whether mental practice with motor imagery is a valid rehabilitation technique in its own right.

The cost of cerebral ischaemia

Cerebral ischaemia is a major cause of disability and death globally and has a profoundly negative impact on the individuals it affects, those that care for them and society as a whole. The most common and familiar manifestation is stroke, 85% of which are ischaemic and which is the second leading cause of death and most common cause of complex chronic disability worldwide. Stroke survivors often suffer from long-term neurological disabilities significantly reducing their ability to integrate effectively in society with all the financial and social consequences that this implies. These difficulties cascade to their next of kin who often become caregivers and are thus indirectly burdened. A more insidious consequence of cerebral ischaemia is progressive cognitive impairment causing dementia which although less abrupt is also associated with a significant long-term disability. Globally cerebrovascular diseases are responsible for 5.4 million deaths every year (1 in 10 of total). Approximately 3% of total healthcare expenditure is attributable to cerebral ischaemia with cerebrovascular diseases costing EU healthcare systems 21 billion euro in 2003. The cost to the wider economy (including informal care and lost productivity) is even greater with stroke costing the UK 7-8 billion pound in 2005 and the US

Does Renal Dysfunction Predict Mortality After Acute Stroke? A 7-Year Follow-Up Study

62.7 billion in 2007. Cerebrovascular disease cost the EU 34 billion euro in 2003. From 2005 to 2050 the anticipated cost of stroke to the US economy is estimated at

A Comparison of Bilateral and Unilateral Upper-Limb Task Training in Early Poststroke Rehabilitation: A Randomized Controlled Trial

2.2 trillion. Given the global scale of the problem and the enormous associated costs it is clear that there is an urgent need for advances in the prevention of cerebral ischaemia and its consequences. Such developments would result in profound benefits for both individuals and their wider societies and address one of the worlds most pre-eminent public health issues.

Prescribing Antiplatelet Medicine and Subsequent Events After Intracerebral Hemorrhage

Background and Purpose— The purpose of this study was to investigate renal function as a long-term predictor of mortality in patients hospitalized for acute stroke. Methods— This was a cohort study done in a Scottish tertiary teaching hospital. Participants included 2042 (993 male) unselected consecutive stroke patients (mean age, 73 years) admitted to hospital within 48 hours of stroke between1988 and 1994. Follow-up was up to 7 years. Main outcome measure was all-cause mortality. Results— The total number of deaths at the end of follow-up was 1026. Most subjects (1512) had creatinine <124 &mgr;mol/L. The mean calculated creatinine clearance was 54.8 mL/min (SD, 23 mL/min). Renal function indexes were analyzed by quartiles with Cox proportional-hazards model. Stroke survivors had higher calculated creatinine clearance and lower serum creatinine, urea, and ratios of urea to creatinine. Calculated creatinine clearance ≥51.27 mL/min significantly predicted better long-term survival in these stroke patients even after adjustment for confounders (age, neurological score, ischemic heart disease, hypertension, smoking, and diuretic use). Similarly, creatinine ≥119 &mgr;mol/L “relative risk (RR), 1.59; 95% confidence interval (CI), 1.32 to 1.92”, urea 6.8 to 8.9 mmol/L (RR, 1.34; 95% CI, 1.09 to 1.65) or ≥9 mmol/L (RR, 1.74; 95% CI, 1.42 to 2.13), and ratio of urea to creatinine ≥0.08573 mmol/&mgr;mol (RR, 1.24; 95% CI, 1.03 to 1.50) remained significant predictors of mortality after adjustment for confounders. Conclusions— After acute stroke, patients with reduced admission calculated creatinine clearance, raised serum creatinine and urea concentrations (even within conventional reference intervals), and raised ratio of urea to creatinine had a higher mortality risk. This finding may be used to stratify risk and target interventions, eg, the use of angiotensin-converting enzyme inhibitors.

Predictive Effects of Different Clinical Balance Measures and the Fear of Falling on Falls in Postmenopausal Women Aged 50 Years and Over

OBJECTIVE To compare the effects of bilateral task training with unilateral task training on upper-limb outcomes in early poststroke rehabilitation. DESIGN A single-blinded randomized controlled trial, with outcome assessments at baseline, postintervention (6 wk), and follow-up (18 wk). SETTING Inpatient acute and rehabilitation hospitals. PARTICIPANTS Patients were randomized to receive bilateral training (n=56) or unilateral training (n=50) at 2 to 4 weeks poststroke onset. INTERVENTION Supervised bilateral or unilateral training for 20 minutes on weekdays over 6 weeks using a standardized program. MAIN OUTCOME MEASURES Upper-limb outcomes were assessed by Action Research Arm Test (ARAT), Rivermead Motor Assessment upper-limb scale, and Nine-Hole Peg Test (9HPT). Secondary measures included the Modified Barthel Index, Hospital Anxiety and Depression Scale, and Nottingham Health Profile. All assessment was conducted by a blinded assessor. RESULTS No significant differences were found in short-term improvement (0-6 wk) on any measure (P>.05). For overall improvement (0-18 wk), the only significant between-group difference was a change in the 9HPT (95% confidence interval [CI], 0.0-0.1; P=.05) and ARAT pinch section (95% CI, 0.3-5.6; P=.03), which was lower for the bilateral training group. Baseline severity significantly influenced improvement in all upper-limb outcomes (P<.05), but this was irrespective of the treatment group. CONCLUSIONS Bilateral training was no more effective than unilateral training, and in terms of overall improvement in dexterity, the bilateral training group improved significantly less. Intervention timing, task characteristics, dose, and intensity of training may have influenced the results and are therefore areas for future investigation.

B-type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors

Background and Purpose— Antiplatelet medicines are commonly perceived as contraindicated after intracerebral hemorrhage (ICH). Many ICH patients have or will have indications for antiplatelet therapy. This observational study describes the level of antiplatelet prescribing and rate of subsequent events after ICH in Tayside, Scotland. Methods— This study used record-linkage of an existing stroke cohort with antiplatelet prescribing data from 1994 to 2005. Patients were followed-up from discharge after index event. The primary outcome was recurrent ICH. Other outcomes were subsequent ischemic stroke and a composite of ischemic stroke or myocardial infarction. Event rates were calculated as the number of events divided by patient-years of exposure. Univariate hazard ratios associated with antiplatelet exposure were derived from a Cox model using a time-dependent covariate. Results— There were 417 ICH patients who survived to discharge. Of these, 120 patients were prescribed subsequent antiplatelet medicines (28.8%). The median time from discharge to antiplatelet use was 14.8 months (range, 2 days-7.5 years). Among all survivors, there were 14 recurrent ICH (rate, 9.7 per 1000 patient-years; 95% confidence interval [CI], 5.3-16.4), 29 subsequent ischemic strokes (rate, 20.6; 95% CI, 13.8-29.6), and 40 subsequent ischemic strokes or myocardial infarctions (rate, 28.7; 95% CI, 20.5-39.0). Hazard ratios associated with antiplatelet exposure were 1.07 (95% CI, 0.24-4.84) for recurrent ICH, 0.23 (95% CI, 0.03-1.68) for ischemic stroke, and 0.72 (95% CI, 0.25-2.02) for ischemic strokes or myocardial infarction. Conclusions— Antiplatelet prescribing was common after ICH. Subsequent ischemic strokes or myocardial infarctions were more common than recurrent ICH. Antiplatelet prescribing did not appear to have a clinically significant impact on outcomes measured. Despite being contraindicated, antiplatelet use was not a major hazard for recurrent ICH.

Recovery of hand function through mental practice: A study protocol

Background: Falls among the elderly are associated with a high morbidity and mortality and can involve high-cost medical interventions. The risk of falls often remains undiagnosed until an episode occurs but if the risk is high, preventative measures could be introduced. Objectives: This 6-month prospective study investigated whether different postural clinical measures and fear of falling (FOF) itself can predict future falls in postmenopausal women aged ≥50 years. Methods: 125 postmenopausal women were studied comparing the outcome of fallers vs. non-fallers within the 6-month follow-up study period. Clinical measures, history of falls and FOF data were determined at baseline and the number of falls and FOF were ascertained at the final visit or by telephone interview at 6 months. Results: Of the clinical measures investigated, the Falls Efficacy Scale International (FES-I) >26 points (OR = 7.28, per additional point, 95% CI 2.25–23.61, p = 0.001) and Berg Balance Scale (BBS) ≤52 points (OR = 4.77, per additional point, 95% CI = 1.15–19.82, p = 0.031) performed best in prediction of the future falls. Conclusions: Postmenopausal women aged ≥50 years who had FES-I scores >26 points and BBS ≤52 points should be examined for risk factors of future falls and offered preventative measures.

Effect of Social Deprivation on Mortality and the Duration of Hospital Stay after a Stroke

Objective: To test the hypothesis that B-type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. Methods: 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. Results: In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman’s r  =  −0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score − rest score; Spearman’s r  =  0.28, two tailed p  =  0.049). In the cohort who did not have left ventricular systolic dysfunction (n  =  44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p  =  0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman’s r  =  0.37 and −0.38, respectively). Conclusions: BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death.