Comparison of Different Laboratory Tests to Identify "Aspirin Resistance" and Risk of Vascular Events among Ischaemic Stroke Patients: A Double-Blind Study.

"Aspirin resistance" (AR) is associated with increased risk of vascular events. We aimed to compare different platelet function tests used in identifying AR and assess their implications on clinical outcome. We performed platelet aggregation studies on non-cardioembolic ischaemic stroke patients taking aspirin 100 mg/day and 30 non-stroke controls. Data were collected on demographics, vascular risk factors, and concomitant medications. Cut-offs for AR were (1) light transmission aggregometry (LTA) of ≥20% using arachidonic acid (AA), ≥70% using ADP, or ≥60% using collagen; and (2) VerifyNow® assay ≥ 550 ARU. Telephone follow-ups were conducted by study staff blinded to AR status to ascertain the occurrence of vascular outcomes (stroke, myocardial infarction, amputation, death). A total of 113 patients were recruited, mean age 65 ± 8 years, 47% women, 45 ± 15 days from index stroke. 50 (44.3%, 95% CI 34.9-53.9) had AR on at least 1 test. Frequency of AR varied from 0% to 39% depending on method used and first vs. recurrent stroke. There were strong correlations between LTA AA, VerifyNow® and Multiplate® ASPItest (r = 0.7457-0.8893), but fair to poor correlation between LTA collagen and Multiplate® COLtest (r = 0.5887) and between LTA ADP and Multiplate® ADPtest (r = 0.0899). Of 103 patients with a mean follow up of 801 ± 249 days, 10 (9.7%) had vascular outcomes, of which six had AR by LTA-ADP. AR by LTA-ADP is associated with increased risk of vascular outcome (p = 0.034). Identification of AR is not consistent across different platelet function tests. LTA of ≥70% using 10 µM ADP in post-stroke patients taking aspirin is associated with increased risk of vascular outcome.

Temporal Trends and Patient Characteristics Associated With Drug Utilisation After First-Ever Stroke: Insights From Chronic Disease Registry Data in Singapore.

INTRODUCTION: Data on drug utilisation among stroke patients of Asian ethnicities are lacking. The objectives of the study were to examine the temporal trends and patient characteristics associated with prescription of thrombolytic, antithrombotic and statin medications among patients with first-ever stroke. MATERIALS AND METHODS: First-ever ischaemic and haemorrhagic stroke patients admitted to 2 Singapore tertiary hospitals between 2010‒2014 were included. Data were extracted from the National Healthcare Group Chronic Disease Management System. Association between drug utilisation and admission year, as well as characteristics associated with drug use, were explored using multivariable logistic regression. RESULTS: There was an increasing trend in the combined use of all 3 guideline medications in ischaemic stroke patients (P <0.001)-specifically thrombolytic agents (P <0.001), oral antithrombotics (P = 0.002) and statins (P = 0.003) at discharge. Among antithrombotics, the use of clopidogrel (P <0.001) and aspirin-clopidogrel (P <0.001) had increased, whereas prescription of dipyridamole (P <0.001) and aspirin-dipyridamole (P <0.001) had declined. For statins, the increase in atorvastatin prescription (P <0.001) was accompanied by decreasing use of simvastatin (P <0.001). Age, ethnicity and certain comorbidities (hyperlipidaemia, atrial fibrillation and chronic kidney disease) were associated with the combined use of all 3 guideline medications (P <0.05). In haemorrhagic stroke, prescription of statins at discharge were comparatively lower. CONCLUSION: This study reveals changes in prescription behaviour over time in a multiethnic Asian population with first-ever stroke. Patient characteristics including younger age, Malay ethnicity and certain comorbidities (i.e. hyperlipidaemia, atrial fibrillation) were associated with the combined use of all 3 guideline medications among ischaemic stroke patients.

Impact of medication nonadherence on stroke recurrence and mortality in patients after first-ever ischemic stroke: Insights from registry data in Singapore.

PURPOSE: This retrospective cohort study aims to examine adherence to secondary stroke preventive medications and their association with risk of stroke recurrence and mortality in patients after first-ever ischemic stroke. METHODS: Using data from the National Healthcare Group and Singapore Stroke Registry, patients with first-ever ischemic stroke between 2010 and 2014 were included, and categorized based on antithrombotic or statin adherence using the proportion of days covered: high (≥75%), intermediate (50%-74%), low (25%-49%), and very low (<25%). The primary outcome was first recurrent ischemic stroke within a year after hospital discharge, while the secondary composite outcomes were (a) stroke recurrence and all-cause mortality and (b) stroke recurrence and cardiovascular mortality. The Cox proportional hazard model was used to examine the association between medication adherence and outcomes. Adjusted hazard ratios (aHRs) and the corresponding 95% confidence intervals (CIs) were reported. RESULTS: Among ischemic stroke patients prescribed with antithrombotics (n = 1139) or statins (n = 1160) at hospital discharge, about one-third were highly adherent to their medications. Patients with lower medication adherence tended to be younger, were admitted to private ward classes, and were without hypertension. Compared with the patients with high medication adherence, the risk of stroke recurrence was higher in patients with very low antithrombotic (aHR = 4.65; 95% CI: 1.45-14.89) or statin (aHR = 3.44; 95% CI: 0.93-12.74) adherence. Similar findings were observed for the secondary outcomes. CONCLUSIONS: Poor adherence to antithrombotic and statin treatment increases the risk of recurrent stroke and mortality in patients after first-ever ischemic stroke. Further measures are needed to improve medication adherence among stroke survivors.

Ministry of Health Clinical Practice Guidelines: Hypertension.

The Ministry of Health (MOH) has updated the clinical practice guidelines on hypertension to provide doctors and patients in Singapore with evidence-based treatment for hypertension. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH clinical practice guidelines on hypertension, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html. The recommendations should be used with reference to the full text of the guidelines. Following this article are multiple choice questions based on the full text of the guidelines.

Detection and Predictors of Paroxysmal Atrial Fibrillation in Acute Ischemic Stroke and Transient Ischemic Attack Patients in Singapore.

BACKGROUND: Detection of paroxysmal atrial fibrillation (pAF) is important for optimal secondary stroke prevention. Data are limited from Asia regarding inpatient occurrence and predictors of pAF to optimize electrocardiographic (ECG) monitoring despite it having nearly two thirds of the world's population and different subtypes of stroke from the West. METHODS: We analyzed a prospective dataset comprising 370 acute ischemic stroke (AIS) and 25 transient ischemic attack (TIA) patients without known atrial fibrillation who underwent continuous ECG monitoring (CEM) in an acute stroke unit from July 2012 to February 2013. The median duration of monitoring was 61 hours. RESULTS: There were 31 cases of pAF. The detection rate was 8% for both AIS and TIA patients. It occurred less often in lacunar infarcts (3%) compared to nonlacunar infarcts (10%) (P = .047). The detection rates in cryptogenic infarcts (10%) and infarcts of known causes (7%) were not significantly different (P = .224). The predictors of pAF according to logistic regression were hemorrhagic conversion (P = .006), scattered infarcts (P = .007), radiological cardiomegaly (P = .007), occlusion of symptomatic artery (P = .023), and older age (P < .001). CONCLUSIONS: pAF occurred in 8% of AIS and TIA in a hospitalized cohort of Asian patients. All patients without known atrial fibrillation should undergo CEM for at least 3 days during hospitalization and priority given to patients with predictors of pAF in centers with resource constraints.

5-year survival and rehospitalization due to stroke recurrence among patients with hemorrhagic or ischemic strokes in Singapore.

BACKGROUND: Stroke is the 4th leading cause of death and 1st leading cause of disability in Singapore. However the information on long-term post stroke outcomes for Singaporean patients was limited. This study aimed to investigate the post stroke outcomes of 5-year survival and rehospitalization due to stroke recurrence for hemorrhagic and ischemic stroke patients in Singapore. The outcomes were stratified by age, ethnic group, gender and stroke types. The causes of death and stroke recurrence were also explored in the study. METHODS: A multi-site retrospective cohort study. Patients admitted for stroke at any of the three hospitals in the National Healthcare Group of Singapore were included in the study. All study patients were followed up to 5 years. Kaplan-Meier was applied to study the time to first event, death or rehospitalization due to stroke recurrence. Cox proportional hazard model was applied to study the time to death with adjustment for stroke type, age, sex, ethnic group, and admission year. Cumulative incidence model with competing risk was applied for comparing the risks of rehospitalization due to stroke recurrence with death as the competing risk. RESULTS: Totally 12,559 stroke patients were included in the study. Among them, 59.3% survived for 5 years; 18.4% were rehospitalized due to stroke recurrence in 5 years. The risk of stroke recurrence and mortality increased with age in all stroke types. Gender, ethnic group and admitting year were not significantly associated with the risk of mortality or stroke recurrence in hemorrhagic stroke. Male or Malay patient had higher risk of stroke recurrence and mortality in ischemic stroke. Hemorrhagic stroke had higher early mortality while ischemic stroke had higher recurrence and late mortality. The top cause of death among died stroke patients was cerebrovascular diseases, followed by pneumonia and ischemic heart diseases. The recurrent stroke was most likely to be the same type as the initial stroke among rehospitalized stroke patients. CONCLUSIONS: Five year post-stroke survival and rehospitalization due to stroke recurrence as well as their associations with patient demographics were studied for different stroke types in Singapore. Specific preventive strategies are needed to target the high risk groups to improve their long-term outcomes after acute stroke.

A controlled study of team-based learning for undergraduate clinical neurology education.

BACKGROUND: Team-based learning (TBL), a new active learning method, has not been reported for neurology education. We aimed to determine if TBL was more effective than passive learning (PL) in improving knowledge outcomes in two key neurology topics - neurological localization and neurological emergencies. METHODS: We conducted a modified crossover study during a nine-week internal medicine posting involving 49 third-year medical undergraduates, using TBL as the active intervention, compared against self-reading as a PL control, for teaching the two topics. Primary outcome was the mean percentage change in test scores immediately after (post-test 1) and 48 hours after TBL (post-test 2), compared to a baseline pre-test. Student engagement was the secondary outcome. RESULTS: Mean percentage change in scores was greater in the TBL versus the PL group in post-test 1 (8.8% vs 4.3%, p = 0.023) and post-test 2 (11.4% vs 3.4%, p = 0.001). After adjustment for gender and second year examination grades, mean percentage change in scores remained greater in the TBL versus the PL group for post-test 1 (10.3% vs 5.8%, mean difference 4.5%,95% CI 0.7 - 8.3%, p = 0.021) and post-test 2 (13.0% vs 4.9%, mean difference 8.1%,95% CI 3.7 - 12.5%, p = 0.001), indicating further score improvement 48 hours post-TBL. Academically weaker students, identified by poorer examination grades, showed a greater increase in scores with TBL versus strong students (p < 0.02). Measures of engagement were high in the TBL group, suggesting that continued improvements in scores 48 hours post-TBL may result from self-directed learning. CONCLUSIONS: Compared to PL, TBL showed greater improvement in knowledge scores, with continued improvement up to 48 hours later. This effect is larger in academically weaker students. TBL is an effective method for improving knowledge in neurological localization and neurological emergencies in undergraduates.

Embolic stroke associated with injection of buprenorphine tablets.

BACKGROUND: Drug users who crush, dissolve, and inject buprenorphine tablets parenterally may be at risk of severe thromboembolic complications or death. We describe patients with neurologic complications after injecting buprenorphine tablets. METHODS: Brain MRI including diffusion-weighted imaging (DWI) in patients admitted to the neurologic department after injecting buprenorphine tablets were reviewed. RESULTS: Seven men had neurologic complications after buprenorphine tablet injection. In 5 patients, multiple small scattered hyperintense lesions were detected on DWI in the cortex, white matter, and basal ganglia of the cerebral hemisphere; one patient had a single small lesion. The side of MRI abnormality corresponded to the side of needle marks on the neck except in one patient who had bilateral injections. One patient, who denied injecting into the neck, had DWI abnormalities in the middle cerebral artery territory on one side and occlusion of the ipsilateral internal carotid artery. CONCLUSIONS: Buprenorphine tablets can be intentionally or inadvertently injected into the carotid artery, causing a characteristic appearance on diffusion-weighted imaging, consistent with embolic cerebral infarction.

Decompression sickness: MRI of the spinal cord.

Decompression sickness (DCS) typically causes changes in the white matter of the spinal cord on MR imaging. We present a case of DCS in a scuba diver with dorsal white matter lesions typical of venous infarction. In addition, some central gray matter involvement was noted. Characteristic features of venous spinal cord infarction can be recognized on MR imaging in DCS but may be more extensive in severe cases.