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BackgroundPatients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolised into its active form by theCYP2C19enzyme. Patients with loss of function (LOF) mutations inCYP2C19are at risk for poorer secondary outcomes when prescribed clopidogrel. We aimed to determine the cost effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population.MethodsMarkov models were developed to look at the cost effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs).ResultsEmpiric treatment with aspirin and ticagrelor was the most cost-effective treatment regimen if the prevalence of LOF was below 7.5%. Genotype guided therapy was more cost effective than empiric aspirin and clopidogrel if the LOF was above 65.5%. Empiric ticagrelor and aspirin was cost saving when compared to genotype guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar.ConclusionThis study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 65.5%.Clinical PerspectiveWhat is new?We show that empiricial ticagrelor and aspirin is the most cost-effective treatment strategy in patients with minor stroke and transient ischemic attackWhat are the clinical implications?In patients with minor stroke/ transient ischemic attack, it may not be necessary to screen forCYP2C19status as empirical ticagrelor and aspirin is cost effective.

Background and Purpose: A third of stroke patients suffer from post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. B-vitamin supplementation provides a possible safe and affordable treatment to mitigate post-stroke neuropsychiatric sequelae via reducing homocysteine levels. Our study aims to examine the effect of B-vitamin supplementation in the prevention of post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. Our secondary aims were to investigate associations between baseline factors and the three outcomes. Methods: Patients were recruited as part of a Singaporean substudy of a randomized controlled trial that examined the effect of B-vitamin supplementation on recurrent cardiovascular events. Cognitive decline, depressive symptoms, and anxiety symptoms were assessed with neuropsychological assessments and Hospital Anxiety and Depression Scale 6 monthly. Cox regression analyses were performed to determine treatment efficacy. Logistic regression used to examine factors associated with cognitive decline, depressive symptoms, and anxiety symptoms. Results: A total of 707 were included in the analyses. Survival and hazards ratio analysis showed no treatment effect of B-vitamins on cognitive decline, depressive symptoms, and anxiety symptoms. Cognitive decline was only associated with age. Depressive symptoms were associated with large anterior cerebral infarcts and hyperlipidemia. Conclusions: Our study showed no benefit of supplementation with B-vitamins for post-stroke cognitive decline, depressive symptoms, or anxiety symptoms. Depressive symptoms were associated with larger anterior cerebral infarcts, which may be reflective of the disability associated with larger infarcts.

Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an in vivo vascular injury model of restenosis. Furthermore, we studied the effects of caffeine in primary human and mouse aortic VSMCs and immortalized mouse aortic VSMCs. Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells. Genetic deletion of the key autophagy gene Atg5, and the Sqstm1/p62 gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy. Interestingly, caffeine also decreased WNT-signaling and the expression of two WNT target genes, Axin2 and Ccnd1 (cyclin D1). This effect was mediated by autophagic degradation of a key member of the WNT signaling cascade, DVL2, by caffeine to decrease WNT signaling and cell proliferation. SQSTM1/p62, MAP1LC3B-II and DVL2 were also shown to interact with each other, and the overexpression of DVL2 counteracted the inhibition of cell proliferation by caffeine. Taken together, our in vivo and in vitro findings demonstrated that caffeine reduced VSMC proliferation by inhibiting WNT signaling via stimulation of autophagy, thus reducing the vascular restenosis. Our findings suggest that caffeine and other autophagy-inducing drugs may represent novel cardiovascular therapeutic tools to protect against restenosis after angioplasty and/or stent placement.

BackgroundSleep disordered breathing (SDB) is an under-recognised independent risk factor and a potential consequence of stroke. We systematically reviewed and meta-analysed the effectiveness of positive airway pressure (PAP) therapy in improving post-stroke outcomes.MethodsWe searched CENTRAL, Embase, PubMed, CINAHL, PsycINFO, Scopus, ProQuest, Web of Science and CNKI (China National Knowledge Infrastructure) for randomised controlled trials comparing PAP therapy against a control or placebo group. We evaluated the pooled effects of PAP therapy on recurrent vascular events, neurological deficit, cognition, functional independence, daytime sleepiness and depression using random effects meta-analyses.ResultsWe identified 24 studies. Our meta-analyses showed that PAP therapy reduced recurrent vascular events (risk ratio 0.47, 95% CI 0.28–0.78), and showed significant beneficial effects on neurological deficit (Hedges’ g= −0.79, 95% CI −1.19– −0.39), cognition (g=0.85, 95% CI 0.04–1.65), functional independence (g=0.45, 95% CI 0.01–0.88) and daytime sleepiness (g= −0.96, 95% CI −1.56– −0.37). However, there was insignificant reduction in depression (g= −0.56, 95% CI −2.15–1.02). No publication bias was detected.ConclusionsPost-stroke patients with SDB benefited from PAP therapy. Prospective trials are needed to determine the ideal initiation period and the minimum effective therapeutic dose.

Patients with ischemic stroke are often treated with clopidogrel monotherapy as part of secondary stroke prevention. The prevalence of loss of function (LOF) mutations in the CYP2C19 gene is higher in Asians than in Western populations. Patients with loss of function (LOF) mutations are at risk for poorer secondary outcomes when prescribed clopidogrel. We aimed to determine the cost effectiveness of genotype-guided antiplatelet therapy in an Asian population with the aim of prescribing ticagrelor as an alternative to patients with LOF mutations. Markov models were developed to look at the cost effectiveness of genetic testing of CYP2C19, with patients who screened positive for LOF alleles being switched to ticagrelor compared to universal clopidogrel treatment. Effect ratios were obtained from the literature and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. Lifetime costs and quality-adjusted life-years (QALYs) were calculated. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). The prevalence of the LOF mutations was 61% in the population, with 65% of ethnic Chinese, 60% of ethnic Indian, and 53% of ethnic Malay patients having LOF mutations. Based on this prevalence, the overall ICER of genetic testing was S$33,839/QALY with ICERS of S$30,755/QALY, S$33,177/QALY, and S$41,470/QALY for Chinese, Indians, and Malays, respectively. This study suggests that it is cost effective to screen for LOF mutations in the CYP2C19 gene in ischemic stroke populations, with ticagrelor as a substitute for clopidogrel in those with LOF mutations.

Highlights • Stroke care is affected during COVID-19 due to infrastructure and manpower changes • Current proposed adaptation of stroke care focuses on hyperacute care • No proposed guide for adaptation of acute stroke unit care during the pandemic • Our adapted acute stroke unit protocol may be useful for adoption or reference, Background Acute stroke unit (ASU) care is proven to reduce mortality and morbidity. During the COVID-19 crisis, established physical units and care practices within existing physical units are likely to be disrupted. Stroke patients with possible suspected COVID-19 infection may be isolated in other wards outside the ASU. Methods Our hospital developed an adapted ASU protocol which includes key elements for stroke unit care, can be utilized by staff not familiar with stroke care with minimal training and can be implemented in various settings. Results The adapted protocol has 3 categories of Acute monitoring (neurological observations, blood pressure and input-output monitoring, investigations and specific post-reperfusion issues), Stroke complications (focusing on 5 common complications) and Unified team (describing daily check-ins, patient education, communication, discharge planning and post-discharge support). Conclusions Details are presented in the article in a format that it can be adopted by other centers facing similar issues in order to ensure ASU care is not compromised.

Background Secondary stroke-prevention strategies proven to reduce stroke recurrence include pharmaceutical agents and lifestyle modifications. Aims We aimed to study factors associated with adherence to medications and lifestyle modifications amongst ischaemic stroke and transient ischaemic attack (TIA) patients. Methods In a prospective cohort study, we surveyed 200 outpatients attending stroke clinic at a Singaporean tertiary hospital. We determined medication knowledge and lifestyle modification adherence through direct questioning. We also administered the Beliefs About Medicines Questionnaire, Trust in Physician Scale, Patient Health Questionnaire and Hospital Anxiety and Depression Scale. Multivariable logistic regression models were used to identify factors associated with adherence. Results The rates of adherence to medications, smoking cessation, dietary modification, and exercise were 52.3%, 71.0%, 80.0% and 78.5% respectively. Subjects who lacked medication knowledge (OR=3.47; 95% CI=1.55-7.74) or possessed negative medication beliefs (OR=1.20; 95% CI=0.72-0.96) were less likely to be adherent to medications. TIA as an index event (OR=5.04; 95% CI=1.39-18.32), younger age (OR=1.04; 95% CI=1.01-1.08) and higher income (OR=2.40; 95% CI=1.09-5.25) were also associated with medication non-adherence. There were no associations between adherence to medications and lifestyle modifications. Dietary adherence was independently associated with exercise adherence (OR=17.2; 95% CI=3.21-92.22). Conclusions Our findings of suboptimal adherence to medications and lifestyle modifications show that many stroke patients are not benefitting from proven secondary stroke prevention strategies. We identified medication knowledge and medication beliefs as potential target areas for studies to improve medication adherence.

The paper demonstrates how a system dynamics approach can support strategic planning of health care services and can in particular help to balance cost-effectiveness considerations with budget impact considerations when assessing a comprehensive package of stroke care interventions in Singapore. A population-level system dynamics model is used to investigate 12 intervention scenarios based on six stroke interventions (a public information campaign, thrombolysis, endovascular therapy, acute stroke unit (ASU), out-of-hospital rehabilitation, and secondary prevention). Primary outcomes included cumulative discounted costs and quality-adjusted life years (QALYs) gained, as well as cumulative net monetary benefit by 2030. All intervention scenarios result in an increase in net monetary benefit by 2030; much of these gains were realized through improved post-acute care. Findings highlight the importance of coordination of care, and affirms the economic value of current stroke interventions.

Air pollution is a global problem and seasonal haze from forest clearing and peat land burning in Indonesia is an annual phenomenon in Southeast Asia. As neurological disorders comprise 6.3% of the burden of disease globally, we reviewed evidence of the association between common neurological conditions and air pollution exposure, and summarised existing data on the impact of the haze phenomenon in Southeast Asia.A PubMed search for relevant studies on air pollution, Alzheimer's disease (AD), dementia, epilepsy, haze, headache, migraine, stroke, Parkinson's disease (PD) and neuromuscular conditions was performed. There were 52 articles which were relevant and were reviewed.There were associations between short-term air pollution exposure with AD, epilepsy, ischaemic stroke and migraine. Long-term air pollution exposure was associated with AD, amyotrophic lateral sclerosis, dementia and ischaemic stroke. Evidence on the link between air pollution and PD was inconsistent. Currently, there is no specific data on the effects haze has on neurological conditions in Southeast Asia.Air pollution is associated with increased risk of certain common neurological disorders. More specific studies are needed to investigate the impact of seasonal haze on neurological conditions in Southeast Asia.

Objectives The efficacy of thrombolytic therapy with tissue plasminogen activator (tPA) is highly time dependent. Although clinical guidelines do not recommend written informed consent as it may cause treatment delays, local policy can supersede and require it. From 2014 to 2017, three out of five public hospitals in Singapore changed from written to verbal consent at different time points. We aimed to examine the association of hospital policy changes regarding informed consent on door-to-needle (DTN) times. Materials and Methods Using data from the Singapore Stroke Registry and surveys of local practice, we analyzed data of 915 acute ischemic stroke patients treated with tPA within 3 hours in all public hospitals between July 2014 to Dec 2017. Patient-level DTN times before and after policy changes were examined while adjusting for clinical characteristics, within-hospital clustering, and trends over time. Results Patient characteristics and stroke severity were similar before and after the policy changes. Overall, the median DTN times decreased from 68 to 53 minutes after the policy changes. After risk adjustment, changing from written to verbal informed consent was associated with a 5.6 minutes reduction (95% CI 1.1-10.0) in DTN times. After the policy changed, the percentage of patients with DTN ≤60 minutes and ≤45 minutes increased from 35.6% to 66.1% (adjusted OR 1.75; 95% CI 1.12-2.74) and 9.3% to 36.0% (adjusted OR 2.42; 95% CI 1.37-4.25), respectively. Conclusion Changing from written to verbal consent is associated with significant improvement in the timeliness of tPA administration in acute ischemic stroke.

Background Health services research aimed at understanding service use and improving resource allocation often relies on collecting subjectively reported or proxy-reported healthcare service utilization (HSU) data. It is important to know the discrepancies in such self or proxy reports, as they have significant financial and policy implications. In high-dependency populations, such as stroke survivors, with varying levels of cognitive impairment and dysphasia, caregivers are often potential sources of stroke survivors’ HSU information. Most of the work conducted on agreement analysis to date has focused on validating different sources of self-reported data, with few studies exploring the validity of caregiver-reported data. Addressing this gap, our study aimed to quantify the agreement across the caregiver-reported and national claims-based HSU of stroke patients. Methods A prospective study comprising multi-ethnic stroke patient and caregiver dyads (N = 485) in Singapore was the basis of the current analysis, which used linked national claims records. Caregiver-reported health services data were collected via face-to-face and telephone interviews, and similar health services data were extracted from the national claims records. The main outcome variable was the modified intraclass correlation coefficient (ICC), which provided the level of agreement across both data sources. We further identified the amount of over- or under-reporting by caregivers across different service types. Results We observed variations in agreement for different health services, with agreement across caregiver reports and national claims records being the highest for outpatient visits (specialist and primary care), followed by hospitalizations and emergency department visits. Interestingly, caregivers over-reported hospitalizations by approximately 49% and under-reported specialist and primary care visits by approximately 20 to 30%. Conclusions The accuracy of the caregiver-reported HSU of stroke patients varies across different service types. Relatively more objective data sources, such as national claims records, should be considered as a first choice for quantifying health care usage before considering caregiver-reported usage. Caregiver-reported outpatient service use was relatively more accurate than inpatient service use over shorter recall periods. Therefore, in situations where objective data sources are limited, caregiver-reported outpatient information can be considered for low volumes of healthcare consumption, using an appropriate correction to account for potential under-reporting. Electronic supplementary material The online version of this article (10.1186/s12913-018-3634-4) contains supplementary material, which is available to authorized users.

Introduction: Knowledge of stroke symptoms is associated with seeking medical attention early, and knowledge of risk factors is an essential factor in stroke prevention. In this study, we evaluated the level of stroke literacy in Singapore. Materials and Methods: A cross-sectional study of Singapore citizens and permanent residents aged 21 years and above was conducted in a public housing estate. Participants were randomly sampled using multi-stage stratified sampling. Assessment of awareness of stroke symptoms and risk factors was performed using open-ended questions. In total, 687 respondents were recruited, with a response rate of 69.7%. Results: Overall, 52.4% of respondents identified the brain as the source of pathology, and 47.6% could cite at least 1 of the 3 FAST symptoms (facial droop, arm weakness and speech difficulty), while 40% could name 2 or more of 7 established risk factors for stroke (high blood pressure, high cholesterol, cigarette smoking, diabetes mellitus, older age, previous heart attacks and stroke). Respondents at higher risk of stroke (older individuals and those with stroke risk factors) did not have greater awareness of stroke symptoms and risk factors. The majority of respondents reported they would seek immediate medical care if they experienced stroke symptoms. Only 59.4% knew the emergency ambulance service telephone number. Conclusion: In a sample of Singaporean adults residing in a public housing estate, we found evidence of poor stroke literacy, highlighting the need for comprehensive population-based education efforts. There is a role for opportunistic education among those at higher risk of stroke. Key words: Health education, Health promotion

Introduction: Earlier treatment with intravenous stroke thrombolysis improves outcomes and lowers risk of bleeding complications. The decision-making and consent process is one of the rate-limiting steps in the duration between hospital arrival and treatment initiation. We aim to describe the attitudes and practices of neurologists in Singapore on the consent and decision-making processes for stroke thrombolysis. Materials and Methods: A survey of neurologists and neurologists-in-training in 2 large tertiary public hospitals in Singapore was conducted. Results: Among 46 respondents, 94% of them considered stroke thrombolysis an emergency treatment and 67% of them indicated there is a need for written informed consent. The majority (87%) knew that from a legal perspective, the doctor should be the decision-maker in an emergency treatment for a mentally incapacitated patient. However, 63% of respondents reported that it is the next-of-kin who usually makes the decision in actual practice. If confronted with a mentally incapacitated stroke patient, 57% of them were willing to be the proxy decision-maker and 13% of them were not. In 3 commonly encountered vignettes when a mentally incapacitated patient was being considered for stroke thrombolysis, there was no clear consensus on the respondents’ practices. Conclusion: The next-of-kin is usually the decision-maker for stroke thrombolysis in practice for a mentally incapacitated patient despite most doctors considering thrombolysis an emergency treatment. This, together with the lack of consensus and variance in decision-making and consent practice amongst neurologists for stroke thrombolysis, demonstrates the need to develop best practice guidelines to standardise healthcare practices for greater consistency in health service delivery. Key words: Emergency treatment, Mentally incapacitated, Proxy decision-maker

Introduction: Intravenous tissue plasminogen activator (tPA) within 3 hours of stroke onset is a licensed proven therapy for ischaemic stroke, with recent trial data showing benefit up to 4.5 hours. We previously published in this journal data of a survey conducted in 2004 showing only 9% of ischaemic stroke patients presenting to the Singapore General Hospital (SGH) arrived within 2 hours of onset. We aimed to determine whether the problem of delayed hospital arrival persists in 2009 and to establish the impact of widening the time window for intravenous tPA to 4.5 hours. Materials and Methods: We prospectively surveyed consecutive ischaemic stroke patients admitted to the SGH from 9th March to 30th April 2009. Patients and/or relatives were interviewed with a standardised form similar to the 2004 survey. Results: Among the 146 ischaemic stroke patients surveyed (median age 67 years, 59% male, median NIHSS score 2), 6% presented to SGH within 2 hours and 15% within 3.5 hours of onset. Median time from stroke onset to hospital arrival was 1245 minutes (20.75 hours). Pre-hospital consultation was significantly associated with hospital arrival after 2 hours from onset. Main reasons cited for delay were not realising the gravity of symptoms (31%) and not recognising them as stroke (27%). Conclusion: Delayed arrival to SGH following acute ischaemic stroke remains a problem in 2009. This confirms the lack of stroke awareness in Singapore and highlights the need for public stroke education. Furthermore, these data confirm that widening the time window for intravenous tPA treatment to 4.5 hours at SGH will increase its utilisation. Key words: Hospital presentation, Singapore, Stroke, Timing

Dystonia is a movement disorder characterized by involuntary, sustained or repetitive, patterned muscle contractions or spasms, frequently causing squeezing and twisting movements or abnormal postures. Dystonic posturing could be one of the accompanying features of epilepsy. We report an elderly lady with intractable focal seizure who presented with more than a year of persistent hand spasms. The clinical importance of differentiating epilepsy from movement disorders is discussed.

Most acute stroke patients with disabilities do not receive recommended rehabilitation following discharge to the community. Functional and social barriers are common reasons for non-adherence to post-discharge rehabilitation. Home rehabilitation is an alternative to centre-based rehabilitation but is costlier. Tele-rehabilitation is a possible solution, allowing for remote supervision of rehabilitation and eliminating access barriers. The objective of the Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) trial is to determine if a novel tele-rehabilitation intervention for the first three months after stroke admission improves functional recovery compared to usual care. This is a single blind (evaluator blinded), parallel, two-arm randomised controlled trial study design involving 100 recent stroke patients. The inclusion criteria are age ≥40 years, having caregiver support and recent stroke defined as stroke diagnosis within 4 weeks. Consenting participants will be randomized with varying block size of 4 or 6 assuming a 1:1 treatment allocation with the participating centre as the stratification factor. The baseline assessment will be done within 4 weeks of stroke onset, followed by follow-up assessments at 3 and 6 months. The tele-rehabilitation intervention lasts for 3 months and includes exercise 5-days-a-week using an iPad-based system that allows recording of daily exercise with video and sensor data and weekly video-conferencing with tele-therapists after data review. Those allocated to the control group will receive usual care. The primary outcome measure is improvement in life task’s social activity participation at three months as measured by the disability component of the Jette Late Life Functional and Disability Instrument (LLFDI). Secondary outcome variables consist of gait speed (Timed 5-Meter Walk Test) and endurance (Two-Minute Walk test), performance of basic activities of daily living (Shah-modified Barthel Index), balance confidence (Activities-Specific Balance Confidence Scale), patient self-reported health-related quality-of-life [Euro-QOL (EQ-5D)], health service utilization (Singapore Stroke Study Health Service Utilization Form) and caregiver reported stress (Zarit Caregiver Burden Inventory). The goal of this trial is to provide evidence on the potential benefit and cost-effectiveness of this novel tele-rehabilitation programme which will guide health care decision-making and potentially improve performance of post-stroke community-based rehabilitation. This trial protocol was registered under ClinicalTrials.gov on 18 July 2013 as study title “The Singapore Tele-technology Aided Rehabilitation in Stroke (STARS) Study” (ID: The STARS Study, ClinicalTrials.gov Identifier: NCT01905917 ).

Introduction: Ethnic Indians have a high burden of vascular disease. Vitamin D deficiency is associated with an increased risk of vascular disease including ischaemic stroke. Vitamin D levels are lower among ethnic Indians compared to ethnic Chinese in healthy individuals. We compared the plasma 25-hydroxyvitamin D [25(OH)D] levels between ethnic Indians and Chinese male ischaemic stroke patients. Methods: We prospectively recruited consecutive ethnic Indian acute ischaemic stroke male patients within seven days of symptom onset, who were admitted to the Singapore General Hospital. The subsequent ethnic Chinese acute ischaemic stroke male patient matched for age and diabetes status was recruited. Plasma 25(OH)D was measured using DiaSorin radioimmunoassay. Results: We studied 22 matched pairs of ethnic Indian and Chinese ischaemic stroke male patients. Mean plasma 25(OH)D level was lower among ethnic Indians (16.7 ± 6.1 μg/L) than ethnic Chinese patients (19.7 ± 4.4 μg/L) ( p=0.04). The mean difference was 2.9 ± 6.46 μg/L corresponding to 12.9 ± 33.1%. Conclusion: Ethnic Indian male ischaemic stroke patients had lower vitamin D levels compared to matched ethnic Chinese counterparts. Thus it is important to consider ethnicity in the understanding of stroke risk due to vitamin D deficiency.

Knowledge of stroke symptoms is associated with seeking medical attention early, and knowledge of risk factors is an essential factor in stroke prevention. In this study, we evaluated the level of stroke literacy in Singapore.A cross-sectional study of Singapore citizens and permanent residents aged 21 years and above was conducted in a public housing estate. Participants were randomly sampled using multi-stage stratified sampling. Assessment of awareness of stroke symptoms and risk factors was performed using open-ended questions. In total, 687 respondents were recruited, with a response rate of 69.7%.Overall, 52.4% of respondents identified the brain as the source of pathology, and 47.6% could cite at least 1 of the 3 FAST symptoms (facial droop, arm weakness and speech difficulty), while 40% could name 2 or more of 7 established risk factors for stroke (high blood pressure, high cholesterol, cigarette smoking, diabetes mellitus, older age, previous heart attacks and stroke). Respondents at higher risk of stroke (older individuals and those with stroke risk factors) did not have greater awareness of stroke symptoms and risk factors. The majority of respondents reported they would seek immediate medical care if they experienced stroke symptoms. Only 59.4% knew the emergency ambulance service telephone number.In a sample of Singaporean adults residing in a public housing estate, we found evidence of poor stroke literacy, highlighting the need for comprehensive population-based education efforts. There is a role for opportunistic education among those at higher risk of stroke.

There is limited utilisation of acute stroke reperfusion treatments which have narrow therapeutic windows, with delayed hospital presentation being a major limiting factor in Singapore. Most patients who wake up with symptoms are ineligible for reperfusion treatments as duration from onset time is not known. We studied the profile of wake-up strokes, onset-to-door duration and their associated factors among ischaemic stroke patients in the context of potential new treatments.This is an observational study of consecutive ischaemic stroke patients presenting within 2 weeks of symptom onset to the Singapore General Hospital in 2012.Of the 642 ischaemic stroke patients studied, 33% of the cases were wake-up strokes [median age 64 years, 88%80 years; median NIHSS score 4, 98%20]. The median onset-to-door duration was 14.3 hours (Interquartile range, 4.8 to 38.2 hours), 20% of them arrived3.5 hours (considering eligibility for intravenous alteplase in the proven 4.5 hours window accounting for a one hour door-to-needle duration), 14%: ≥3.5 to8 hours, 11%: ≥8 to12 hours, and 56%: ≥12 hours. Most patients with known stroke risk factors including atrial fibrillation (66%), hypertension (78%) and prior stroke (81%) presented beyond 3.5 hours.The one- third proportion of wake-up stroke in this cohort and low prevalence of relative contraindications suggest this is a promising group for emerging thrombolysis indications. With the majority of patients presenting after 8 hours, widening of the therapeutic window with new potential reperfusion treatments would not appreciably increase treatment utilisation. This study reaffirms the urgent need for public education to improve stroke awareness in Singapore.

SummaryBackgroundEpidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye.MethodsIn this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0·5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratified by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT00097669, and Current Controlled Trials, ISRCTN74743444.FindingsBetween Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3·4 years (IQR 2·0–5·5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0·91, 95% CI 0·82 to 1·00, p=0·05; absolute risk reduction 1·56%, −0·01 to 3·16). There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups.InterpretationDaily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the effect of B vitamins.FundingAustralia National Health and Medical Research Council, UK Medical Research Council, Singapore Biomedical Research Council, Singapore National Medical Research Council, Australia National Heart Foundation, Royal Perth Hospital Medical Research Foundation, and Health Department of Western Australia.

Introduction: Coronary artery disease (CAD) is the leading cause of death following ischaemic stroke. We aimed to study the prevalence and associations of concomitant CAD among ischaemic stroke patients in Singapore. Materials and Methods: We prospectively studied 2686 consecutive Asian ischaemic stroke patients. Results: CAD was prevalent among 24% of the study patients. Older age, hypertension, diabetes, hyperlipidaemia, atrial fibrillation, large stroke and South Asian ethnicity were independently associated with CAD. Conclusions: The variables found to be associated with CAD are known atherosclerotic risk factors (older age, hypertension, diabetes, hyperlipidaemia) or associations of cardioembolic stroke (atrial fibrillation, large stroke). The over-representation of South Asians with concomitant CAD is consistent with the high burden of CAD in this ethnic group. Key words: Associations, Atherosclerosis, Risk factors

Introduction: Intravenous thrombolysis has been shown to improve outcome after acute cerebral infarction if given within 3 hours of symptom onset. There are no data in Singapore on the timing of hospital presentation after acute cerebral infarction as well as factors and reasons for delayed presentation. Materials and Methods: As intravenous thrombolysis has recently been licensed for use in acute cerebral infarction in Singapore, we studied 100 consecutive acute cerebral infarction admitted to the Singapore General Hospital for timing of hospital presenta-tion, reasons associated with delay in presentation and hypothetical acceptance of intravenous thrombolysis. Results: Only 9% of patients presented to hospital within 2 hours of symptom onset. Factors associated with hospital presentation within 2 hours were a large stroke and lack of pre-hospital consultation. Failure to recognise the severity of symptoms and inability to seek medical attention unaided were the 2 most common reasons for delayed presentation. One-third of patients or their relatives hypothetically would accept intravenous thrombolysis, suggesting that a thrombolysis service is feasible at the Singapore General Hospital. However, it would be hindered by the low proportion of patients who present early to hospital after symptom onset. Conclusion: Our results support the need for a public education programme to highlight the identification of stroke symptoms and the need to present to hospital as soon as possible after the onset of stroke symptoms. Key words: Delayed, Singapore, Stroke

Cefasporins such as cefepime are beta-lactam antibiotics with a broad antimicrobial spectrum. They are commonly used as first-line agents in the treatment of many infections.1 Reversible encephalopathy is a known neurotoxic complication of cefalosporins.2 Previous case reports have documented triphasic waves on electroencephalography (EEG) in cephalosporin-induced encephalopathy.1-4 Cefalosporin-induced encephalopathy with triphasic waves has not been previously reported among Asians. We report 3 Asian patients with toxic encephalopathy and documented triphasic waves on EEG while on treatment with cefepime.