Persistence, adherence and outcomes with antiplatelet regimens following cerebral infarction in the Tayside Stroke Cohort.

BACKGROUND: Co-prescribed aspirin and dipyridamole are more effective than aspirin alone following cerebral infarction; however, patients may struggle with this more complex regimen. The objectives of this study were: (1) to describe postdischarge prescribing of antiplatelet regimens, (2) to measure patient persistence with different antiplatelet regimens, and (3) to measure whether persistence impacts on outcomes. METHODS: We used record linkage of the Tayside Stroke Cohort with community dispensed prescribing data from 1994 to 2005. All patients had suffered a radiologically confirmed cerebral infarction and were excluded if they had previously used or had other indications for antiplatelet agents. We measured persistence to initial and any antiplatelet regimen using survival analysis. To assess the impact of therapy we used survival analysis to follow up until the APTC endpoint of serious vascular event (myocardial infarction, stroke or vascular death) or censored. Antiplatelet regimen was entered as a time-dependent covariate in a Cox model that also adjusted for age, sex, history of diabetes and baseline use of nitrates and statins. RESULTS: The study cohort contained 1,407 stroke patients (mean age 70.3 years, 46.8% male), with a total follow-up of 4,243 patient-years. Patients initiated on aspirin with dipyridamole had a worse persistence to their initial regimen compared with those initiated on aspirin alone (hazard ratio for non-persistence 1.62; 95% CI 1.37-1.92), but better persistence with any antiplatelet medication long term (hazard ratio 0.86; 95% CI 0.73-1.02). Compared to aspirin monotherapy, receiving no antiplatelet therapy was associated with significantly worse patient outcomes (hazard ratio 1.50; 95% CI 1.21-1.87), whilst receiving prescribed aspirin with dipyridamole was associated with better outcomes (hazard ratio 0.75; 95% CI 0.56-0.99). Only a few patients received clopidogrel or other antiplatelet regimens. CONCLUSIONS: Patients discharged on dual therapy have worse adherence to their initial regimen but better persistence to any antiplatelet agents in the long term. Continued exposure to antiplatelet regimens predicts good outcomes in patients with cerebral infarction.

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.

Prescribing antiplatelet medicine and subsequent events after intracerebral hemorrhage.

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.

Predicting mortality using two renal function estimation methods in hospitalised stroke patients.

The prognostic abilities of the MDRD and Cockcroft-Gault methods for estimating renal function were compared in a cohort study of 1287 patients with acute stroke admitted to a Scottish tertiary care teaching hospital. Using Cox regression analysis corrected for other prognostic variables, both the MDRD and Cockcroft-Gault equations predicted mortality independently of other prognostic factors. A 1 ml/min reduction in GFR as calculated by MDRD was associated with a 1.0% (95% CI: 0.3-1.6) increase in risk of death. A 1 ml/min reduction in creatinine clearance from the Cockcroft-Gault equation was associated with a 1.7% (95% CI: 0.9-2.6) increase in risk of death. The Cockcroft-Gault equation weakly predicted length of stay (r=0.066, p=0.02, Spearman's rank test). In conclusion, both methods independently predict early and late mortality in stroke patients, but the Cockcroft-Gault estimate has greater predictive power in this population.

Predictive effects of different clinical balance measures and the fear of falling on falls in postmenopausal women aged 50 years and over.

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 > or =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) < or =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 > or =50 years who had FES-I scores >26 points and BBS < or =52 points should be examined for risk factors of future falls and offered preventative measures.

A comparison of bilateral and unilateral upper-limb task training in early poststroke rehabilitation: a randomized controlled trial.

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.

Recovery of hand function through mental practice: a study protocol.

BACKGROUND: The study aims to assess the therapeutic benefits of motor imagery training in stroke patients with persistent 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 the redistribution of brain activity, which accompanies recovery of hand function, thus resulting in a reduced motor deficit. METHODS/DESIGN: A multi-centre randomised controlled trial recruiting individuals between one and six months post-stroke (n = 135). Patients are assessed before and after a four-week evaluation period. In this trial, 45 patients daily mentally rehearse movements with their affected arm under close supervision. Their recovery is compared to 45 patients who perform closely supervised non-motor mental rehearsal, and 45 patients who are not engaged in a training program. Motor imagery training effectiveness is evaluated using outcome measures of motor function, psychological processes, and level of disability. DISCUSSION: The idea of enhancing motor recovery through the use of motor imagery rehabilitation techniques is important with potential implications for clinical practice. The techniques evaluated as part of this randomised controlled trial are informed by the current understanding in cognitive neuroscience and the trial is both of scientific and applied interest.

A preliminary investigation into tooth care, dental attendance and oral health related quality of life in adult stroke survivors in Tayside, Scotland.

OBJECTIVE: The aim of this study was to investigate patterns of oral care, dental attendance and oral health-related quality of life among adults who had suffered a stroke. BACKGROUND: Stroke is the most common cause of adult disability in the UK. Seventy per cent of strokes occur in adults over 65 years of age. A mild stroke may leave little residual disability but in cases of moderate or severe stroke the disability may be significant and may impact on oral health and function. MATERIALS AND METHODS: A cross-sectional survey was conducted among adults surviving 1 year after stroke, between January and July 2001. A medical screening was carried out which included an assessment of disability and handicap using the modified Rankin scale. A structured interview was conducted to identify normal patterns of oral care and dental attendance and to elicit if since suffering a stroke any changes had occurred or were likely to occur. The Short Form Oral Health Impact Profile (OHIP-14) was administered prior to an oral examination. Analysis used SPSS 11.0 for Windows. Parametric and nonparametric tests were undertaken (t-tests and chi-squared tests with Yates correction where appropriate). RESULTS: Forty-one adults were recruited into the study comprising 21 female and 20 male. They ranged in age from 50 to 87 years and the mean age was 69 years (SD = 9.8). Forty per cent of participants experienced moderate disability or greater following their stroke. Thirty-seven per cent had difficulty with tooth cleaning. The most frequently reported problem was being unable to use one hand properly as a result of the stroke. There was a significant association between the degree of disability following stroke and difficulty with tooth cleaning (P = 0.015). Disability as a result of the stroke was cited as the main reason for reported or projected attendance pattern change. The most frequently experienced OHIP-14 dimension was functional limitation (39%). CONCLUSION: Individuals who have been left disabled after a stroke may require help with or advice on oral care and information on how to access dental services in a setting appropriate to their disability. Further research is needed to identify the dental needs of adults with stroke and to identify appropriate interventions to meet these needs.

Orlistat enhances warfarin effect.

OBJECTIVE: To report a case of increased international normalized ratio (INR) associated with the addition of orlistat to the drug regimen of a patient receiving warfarin therapy. CASE SUMMARY: A 66-year-old white man with a history of chronic atrial fibrillation (treated with a stable dose of warfarin), hypertension, and diet-controlled type 2 diabetes mellitus was started on orlistat for weight reduction. An increased INR was reported after the introduction of orlistat; there had been no other recent changes to medication or medical conditions. Warfarin was withheld and the dose reduced to allow INR control to be reestablished. According to the Naranjo probability scale, this reaction was probable. DISCUSSION: Control of the INR within therapeutic limits is always a challenge. Dietary intake of vitamin K, intercurrent illness, concomitant medication, herbal remedies, and other factors can interfere with warfarin dosing. Orlistat use may be associated with patient alteration of diet to compensate for adverse effects or other mechanisms by which orlistat alters warfarin control, including direct effect on absorption of vitamin K. CONCLUSIONS: The introduction of chronic dosing of orlistat may reduce the absorption of fat-soluble vitamins, including vitamin K, with the result that a lower dose of warfarin may be required. This may be due in part to change to a lower fat diet with decreased amounts of vitamin K. It may also be due to an effect on vitamin K absorption. Caution should be exercised when these 2 drugs are used concurrently.

A benefit-risk assessment of agents used in the secondary prevention of stroke.

Stroke is a major cause of morbidity and mortality. Full assessment of stroke or transient ischaemic attack (TIA) patients is required to identify all risk factors and apply appropriate secondary preventative strategies. Antiplatelet therapies are effective in the secondary prevention of ischaemic stroke and can be justified despite adverse effects such as gastrointestinal haemorrhage. Aspirin (acetylsalicylic acid), aspirin plus dipyridamole, ticlopidine and clopidogrel are all of value but their adverse effect profiles vary significantly. Combinations of antiplatelet agents may offer additional benefit but not all combinations have been studied in stroke patients. Anticoagulation with agents such as warfarin is effective with coexisting atrial fibrillation and other conditions predisposing to cardioembolic stroke. Antihypertensive agents have been extensively studied in the primary prevention of stroke; however, relatively few trials of antihypertensive agents in the secondary prevention of stroke are available. The incidence of adverse effects of antihypertensive agents is relatively low and the benefit-risk profile would tend to favour their use in the secondary prevention of stroke. Recent studies of ACE inhibitors have identified an important role for these agents in the secondary prevention of stroke even in those who are normotensive and in those who have had a haemorrhagic stroke. The incidence of serious adverse effects with ACE inhibitors appears relatively low. Lipid-lowering agents may have a role to play in certain groups of patients with stroke. The incidence of adverse effects is relatively low with HMG-CoA reductase inhibitors. Cigarette smoking is an important risk factor for stroke and evidence is available that smoking cessation does reduce the individual's risk of stroke. Pharmacological agents are available to help smoking cessation. In patients with diabetes mellitus, intensive regimens with insulin and oral hypoglycaemic agents have so far not definitively been shown to reduce the incidence of macrovascular complications such as stroke. Tight glycaemic control has been shown to improve microvascular complications such as retinopathy, nephropathy and neuropathy and hence this is reason enough to advocate the use of these agents. Future developments in the treatment of diabetes may help. Secondary prevention of stroke has improved greatly over the past decade and hopefully will continue to improve. The use of pharmacological agents available currently and in the future will be clarified and refined as further clinical trials report.

Does renal dysfunction predict mortality after acute stroke? A 7-year follow-up study.

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 between 1988 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 micromol/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 > or =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 > or =119 micromol/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 > or =9 mmol/L (RR, 1.74; 95% CI, 1.42 to 2.13), and ratio of urea to creatinine > or =0.08573 mmol/micromol (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.