Qualitative study exploring heterogeneity in caregiving experiences post-stroke in Singapore.

OBJECTIVE: Stroke, a common illness in older adults, accounts for up to 4% of direct medical costs in developed nations. Informal caregiving contributing a significant proportion of economic burden post-stroke warrants a deeper understanding of the caregiving context to sustain caregiving arrangement. While literature exists describing differences in motivation and preferences of caregivers, limited literature explores differences in caregiving experiences of different types of caregivers (ie, spouse, adult-child, sibling or others). Addressing this gap, our study aimed to explore the caregiving experience of stroke survivors and their family caregivers across different caregiver identities in an Asian setting. DESIGN: Qualitative descriptive study. SETTING: Community setting. PARTICIPANTS: We conducted semi-structured interviews with 26 stroke survivors and 35 caregivers purposively sampled from an outpatient rehabilitation setting, an outpatient clinic and a support organisation. Data were analysed using thematic analysis. OUTCOME MEASURES: Themes including caregiving experience of stroke survivors and their family caregivers across different caregiver identities. RESULTS: Following five themes were reported: caregiver reserve, coping strategies, caregiver burden, competing commitments and role of foreign domestic worker (FDW) in family caregiving. Spouse caregivers were less willing to ask for help, commonly adopted faith-based, and spacing or recharging types of coping, reported emotional strain and shared limited accounts of FDWs. Adult-child caregivers were more willing to ask for help, engaged in alternative care arrangements involving FDWs, commonly adopted action-focussed coping and reported multidimensional caregiver burden. CONCLUSION: Our findings illustrated the heterogeneity in factors affecting caregiving experience across spouse and adult-child caregivers. Practical implications include conducting a needs assessment for caregiver-stroke survivor dyads and providing tailored support, training and information to help caregivers cope better.

Seeking healthcare services post-stroke: a qualitative descriptive study exploring family caregiver and stroke survivor perspectives in an asian setting.

AIM: Exploration of the healthcare journey post-stroke is incomplete without acknowledging the crucial role of family caregivers. With limited literature documenting the role of caregivers in the healthcare journey post-stroke, we aimed to describe the healthcare experiences of family caregivers and stroke survivors across different caregiver identities in Singapore. METHODS: We conducted a qualitative descriptive study involving semi-structured interviews with transcripts analysed using thematic analysis. 26 stroke survivors and 35 family caregivers purposively sampled from multiple settings. RESULTS: Findings were summarized into seeking care and experience of healthcare encounters. Seeking care comprised of the following themes: factors influencing seeking care, decision to seek care and role of caregiver in seeking care. Experience of healthcare encounters comprised of the following themes: service around the patient, service with care and role of caregiver in healthcare encounters. CONCLUSION: Multi-dimensional role of caregivers in healthcare experience emerged as a major finding. Unique to our Asian context, as per the participants' accounts, family caregivers seemed to be central in healthcare decision-making for stroke survivors, with adult-child caregivers commonly reported being engaged in collaborative decision-making. While spousal caregivers preferred a relational healthcare experience, adult-child caregivers preferred a transactional one. Practical implications include equipping caregivers with skillset to make healthcare decisions, provision of supportive decision-making environment for caregivers and reinforcing communication aspects in the medical, nursing and allied healthcare curriculum to improve healthcare experience.

Support system diversity among family caregivers of stroke survivors: a qualitative study exploring Asian perspectives.

BACKGROUND: Caregiving is a global phenomenon which is bound to increase in tandem with the aging population worldwide. Stroke is a condition common in older people that requires complex caregiving necessitating provision of adequate support to the caregivers. Past literature consists of limited accounts of types and organization of support arrangements needed by different caregivers. We aimed to describe the support system of caregivers of stroke survivors in Singapore, highlighting differences across the different caregiver identities (i.e. spouse, adult-child, etc.). METHODS: We conducted a qualitative descriptive study in the community setting involving 61 purposively sampled and recruited stroke survivors and caregivers. Semi-structured interviews were conducted, and transcripts were analysed using thematic analysis. RESULTS: Our findings were summarized across the following 4 themes: 1) cultural influence and caregiving; 2) caregiver support system with the following sub-themes: 2.1) dyadic caregiver support type, 2.2) extended caregiver support type, 2.3.) distributed caregiver support type and 2.4) empowering caregiver support type; 3) breaks in care of stroke survivor and 4) complex relationship dynamics. We operationalized the caregiver support system as comprising of type, people and activities that enable the caregiver to participate in caregiving activities sustainably. While spouse caregivers preferred dyadic and extended support systems positioning themselves in a more central caregiving role, adult-child caregivers preferred distributed support system involving family members with paid caregivers playing a more central role. CONCLUSIONS: Our findings highlight caregiver identity as a surrogate for the differences in the caregiver support systems. Practical implications include imparting relationship-building skills to the stroke survivor-caregiver dyads to sustain dyadic support system and educating clinicians to include differences in caregiving arrangements of stroke survivors in practising family-centred care.

Role of caregiver factors in outpatient medical follow-up post-stroke: observational study in Singapore.

BACKGROUND: Outpatient medical follow-up post-stroke is not only crucial for secondary prevention but is also associated with a reduced risk of rehospitalization. However, being voluntary and non-urgent, it is potentially determined by both healthcare needs and the socio-demographic context of stroke survivor-caregiver dyads. Therefore, we aimed to examine the role of caregiver factors in outpatient medical follow-up (primary care (PC) and specialist outpatient care (SOC)) post-stroke. METHOD: Stroke survivors and caregivers from the Singapore Stroke Study, a prospective, yearlong, observational study, contributed to the study sample. Participants were interviewed 3-monthly for data collection. Counts of PC and SOC visits were extracted from the National Claims Database. Poisson modelling was used to explore the association of caregiver (and patient) factors with PC/SOC visits over 0-3 months (early) and 4-12 months (late) post-stroke. RESULTS: For the current analysis, 256 stroke survivors and caregivers were included. While caregiver-reported memory problems of a stroke survivor (IRR: 0.954; 95% CI: 0.919, 0.990) and caregiver burden (IRR: 0.976; 95% CI: 0.959, 0.993) were significantly associated with lower early post-stroke PC visits, co-residing caregiver (IRR: 1.576; 95% CI: 1.040, 2.389) and negative care management strategies (IRR: 1.033; 95% CI: 1.005, 1.061) were significantly associated with higher late post-stroke SOC visits. CONCLUSION: We demonstrated that the association of caregiver factors with outpatient medical follow-up varied by the type of service (i.e., PC versus SOC) and temporally. Our results support family-centred care provision by family physicians viewing caregivers not only as facilitators of care in the community but also as active members of the care team and as clients requiring care and regular assessments.

Dyadic approach to post-stroke hospitalizations: role of caregiver and patient characteristics.

AIM: To study the association of caregiver factors and stroke patient factors with rehospitalizations over the first 3 months and subsequent 3-12 months post-stroke in Singapore. METHODS: Patients with stroke and their caregivers were recruited in the Singapore Stroke Study, a prospective yearlong cohort. While caregiver and patient variables were taken from this study, hospitalization data were extracted from the national claims database. We used Poisson modelling to perform bivariate and multivariable analysis with counts of hospitalization as the outcome. RESULTS: Two hundred and fifty-six patient with stroke and caregiver dyads (N = 512) were analysed, with patients having spouse (60%), child (29%), sibling (4%) and other (7%) as their caregivers. Among all participants, 89% of index strokes were ischemic, 57% were mild in severity and more than half (59%) of the patients had moderate or severe disability post-stroke as measured on the Modified Rankin Scale. Having social support in the form of a foreign domestic worker for general help of caregiver reduced the hospitalization rate over 3 months post-stroke by 66% (IRR: 0.342; 95% CI: 0.180, 0.651). Compared to having a spousal caregiver, those with a child caregiver had an almost three times greater rate of hospitalizations over 3-12 months post-stroke (IRR: 2.896; 95% CI: 1.399, 5.992). Higher reported caregiving burden at the 3-month point was associated with the higher subsequent rate of hospitalization. CONCLUSION: Recommendations include the adoption of a dyadic or holistic approach to post-stroke care provision by healthcare practitioners, giving due importance to both patients with stroke and their caregivers, integrating caregivers in the healthcare system to extend the care continuum to include informal care in the community and provision of timely support for caregivers.

Health-related quality of life loss associated with first-time stroke.

OBJECTIVES: This study aimed to quantify health-related quality of life (HRQoL) loss associated with first episode of stroke by comparing patient-reported HRQoL before and after stroke onset. The impact of stroke in local population was also evaluated by comparing the pre- and post-stroke HRQoL with that of the general population. METHODS: The HRQoL of stroke survivors was assessed with the EQ-5D-3L index score at recruitment, for recalled pre-stroke HRQoL, and at 3 and 12 month post-stroke. Change in HRQoL from pre-stroke to 3 and 12 month was self-reported by 285 and 238 patients, respectively. Mean EQ index score at each time point (baseline: 464 patients; 3 month post-stroke: 306 patients; 12 month post-stroke: 258 patients) was compared with published population norms for EQ-5D-3L. RESULTS: There was a significant decrease in HRQoL at 3 (0.25) and 12 month (0.09) post-stroke when compared to the retrospectively recalled patients' mean pre-stroke HRQoL level (0.87). The reduction at 3 month was associated with the reduction in all EQ-5D-3L health dimensions; reductions remaining at 12 month were limited to dimensions of mobility, self-care, usual activities, and anxiety/depression. Stroke patients had a lower mean EQ index than the general population by 0.07 points pre-stroke (0.87 vs. 0.94), 0.33 points at 3 month (0.61 vs. 0.94) and 0.18 points at 12 month (0.76 vs. 0.94) post-stroke. CONCLUSIONS: Stroke has a substantial impact on HRQoL in Singapore, especially in the first three months post-stroke. Compared to the general population, stroke survivors have lower HRQoL even before stroke onset. This pre-stroke deficit in HRQoL should be taken into account when quantifying health burden of stroke or setting goals for stroke rehabilitation.

Medication compliance in Singaporean patients with Alzheimer's disease.

INTRODUCTION: Singapore has a rapidly ageing population and an increasing prevalence of Alzheimer's disease (AD). Compliance to AD medications is associated with treatment effectiveness. We investigated compliance to acetylcholinesterase inhibitors (AChEIs) and N-methyl-D-aspartate (NMDA) receptor antagonist and treatment persistence among patients seen at the General Memory Clinic of National University Hospital, Singapore. We also identified the reasons for non-compliance. METHODS: Patients seen at the General Memory Clinic between 1 January 2013 and 31 December 2014, who were prescribed AChEIs and NMDA receptor antagonist, were included in this retrospective cohort study. Non-compliance to medications was indirectly measured by failure to renew prescription within 60 days of the last day of medication supplied by the previous prescription. The reasons for non-compliance were identified. RESULTS: A total of 144 patients were included. At one year, 107 patients were compliant to AD medications, while 37 patients were non-compliant. Around 60% of the non-compliant patients discontinued the use of AD medications within the first six months, and the mean persistent treatment period among this group of patients was 10.3 ± 3.5 months. The main reason for non-compliance was patients' and caregivers' perception that memory loss was of lower priority than other coexisting illnesses. Other reasons for non-compliance included side effects of medications (18.9%), perceived ineffectiveness of treatment (16.2%), inability to attend clinic (5.4%) and high cost of medications (2.7%). CONCLUSION: Our findings suggest that the reasons for medication non-compliance can be identified early. Better compliance may be achieved through a multidisciplinary approach to patient education.

Healthcare utilization and cost trajectories post-stroke: role of caregiver and stroke factors.

BACKGROUND: It is essential to study post-stroke healthcare utilization trajectories from a stroke patient caregiver dyadic perspective to improve healthcare delivery, practices and eventually improve long-term outcomes for stroke patients. However, literature addressing this area is currently limited. Addressing this gap, our study described the trajectory of healthcare service utilization by stroke patients and associated costs over 1-year post-stroke and examined the association with caregiver identity and clinical stroke factors. METHODS: Patient and caregiver variables were obtained from a prospective cohort, while healthcare data was obtained from the national claims database. Generalized estimating equation approach was used to get the population average estimates of healthcare utilization and cost trend across 4 quarters post-stroke. RESULTS: Five hundred ninety-two stroke patient and caregiver dyads were available for current analysis. The highest utilization occurred in the first quarter post-stroke across all service types and decreased with time. The incidence rate ratio (IRR) of hospitalization decreased by 51, 40, 11 and 1% for patients having spouse, sibling, child and others as caregivers respectively when compared with not having a caregiver (p = 0.017). Disability level modified the specialist outpatient clinic usage trajectory with increasing difference between mildly and severely disabled sub-groups across quarters. Stroke type and severity modified the primary care cost trajectory with expected cost estimates differing across second to fourth quarters for moderately-severe ischemic (IRR: 1.67, 1.74, 1.64; p = 0.003), moderately-severe non-ischemic (IRR: 1.61, 3.15, 2.44; p = 0.001) and severe non-ischemic (IRR: 2.18, 4.92, 4.77; p = 0.032) subgroups respectively, compared to first quarter. CONCLUSION: Highlighting the quarterly variations, we reported distinct utilization trajectories across subgroups based on clinical characteristics. Caregiver availability reducing hospitalization supports revisiting caregiver's role as potential hidden workforce, incentivizing their efforts by designing socially inclusive bundled payment models for post-acute stroke care and adopting family-centered clinical care practices.

Can acute clinical outcomes predict health-related quality of life after stroke: a one-year prospective study of stroke survivors.

BACKGROUND: Health-related quality of life (HRQoL) is a key metric to understand the impact of stroke from patients' perspective. Yet HRQoL is not readily measured in clinical practice. This study aims to investigate the extent to which clinical outcomes during admission predict HRQoL at 3 months and 1 year post-stroke. METHODS: Stroke patients admitted to five tertiary hospitals in Singapore were assessed with Shah-modified Barthel Index (Shah-mBI), National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Mini-Mental State Examination (MMSE), and Frontal Assessment Battery (FAB) before discharge, and the EQ-5D questionnaire at 3 months and 12 months post-stroke. Association of clinical measures with the EQ index at both time points was examined using multiple linear regression models. Forward stepwise selection was applied and consistently significant clinical measures were analyzed for their association with individual dimensions of EQ-5D in multiple logistic regressions. RESULTS: All five clinical measures at baseline were significant predictors of the EQ index at 3 months and 12 months, except that MMSE was not significantly associated with the EQ index at 12 months. NIHSS (3-month standardized ß = - 0.111; 12-month standardized ß = - 0.109) and mRS (3-month standardized ß = - 0.122; 12-month standardized ß = - 0.080) were shown to have a larger effect size than other measures. The contribution of NIHSS and mRS as significant predictors of HRQoL was mostly explained by their association with the mobility, self-care, and usual activities dimensions of EQ-5D. CONCLUSIONS: HRQoL at 3 months and 12 months post-stroke can be predicted by clinical outcomes in the acute phase. NIHSS and mRS are better predictors than BI, MMSE, and FAB.

Can caregivers report their care recipients' post-stroke hospitalizations and outpatient visits accurately? Findings of an Asian prospective stroke cohort.

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.

Cerebellar strokes: a clinical outcome review of 79 cases.

INTRODUCTION: Cerebellar infarcts and haemorrhages are relatively uncommon, accounting for less than 10% of all strokes. The objective of the present study was to quantify and compare the outcomes of patients with cerebellar infarct and those of patients with cerebellar haemorrhage, as well as to identify the risk factors that predict poor outcome in patients with cerebellar stroke. METHODS: We retrospectively reviewed the medical records of consecutive patients admitted to National University Hospital, Singapore, between 2004 and 2006, within one week of cerebellar stroke onset. Baseline data included demographics, concomitant comorbidities, and the presence or absence of brainstem compression and hydrocephalus (on computed tomography or magnetic resonance imaging). The Glasgow Outcome Scale and modified Rankin Score were used to assess outcome at discharge and at six months after discharge. RESULTS: A total of 79 patients with cerebellar stroke were admitted during the study period. Of these 79 patients, 17.7% died and 31.6% had poor outcomes at six months after discharge. Patients with cerebellar haemorrhage were found to be more likely to have poor outcomes as compared to patients with cerebellar infarct, both at discharge (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.3-14.1) and at six months after discharge (OR 5.2, 95% CI 1.6-17.2). When compared to small lesions (< 5 cm(3)), lesions > 20 cm(3) were significantly associated with poorer outcomes and the development of hydrocephalus and brainstem compression. CONCLUSION: Cerebellar strokes are a significant cause of morbidity and mortality. The outcomes of patients with cerebellar haemorrhage are more likely to be worse than those of patients with cerebellar infarct.

Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder with emerging evidence that it is associated with retinal ganglion cell loss; however, few data exist to establish this association. OBJECTIVE: To determine whether macular ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL), as quantitatively measured by non-invasive in vivo spectral-domain optical coherence tomography (SD-OCT), are altered in patients with AD and mild cognitive impairment (MCI). METHODS: Patients with AD and MCI were recruited from dementia/memory clinics, and cognitively normal controls were selected from the Singapore Epidemiology of Eye Disease program. SD-OCT (Cirrus HD-OCT, software version 6.0.2, Carl Zeiss Meditec Inc, Dublin, CA) was used to measure the GC-IPL and RNFL thicknesses. RESULTS: Compared with cognitively normal controls (n = 123), patients with AD (n = 100) had significantly reduced GC-IPL thicknesses in all six (superior, superonasal, inferonasal, inferior, inferotemporal, and superotemporal) sectors (mean differences from -3.42 to -4.99 µm, all p < 0.05) and reduced RNFL thickness in superior quadrant (-6.04 µm, p = 0.039). Patients with MCI (n = 41) also had significantly reduced GC-IPL thicknesses compared with controls (mean differences from -3.62 to -5.83 µm, all p < 0.05). Area under receiver operating characteristic curves of GC-IPL were generally higher than that of RNFL to discriminate AD and MCI from the controls. CONCLUSIONS: Our data strengthens the link between retinal ganglion cell neuronal and optic nerve axonal loss with AD, and suggest that assessment of macular GC-IPL can be a test to detect neuronal injury in early AD and MCI.

Assessment of intracranial collaterals on CT angiography in anterior circulation acute ischemic stroke.

BACKGROUND AND PURPOSE: Intracranial collaterals influence the prognosis of patients treated with intravenous tissue plasminogen activator in acute anterior circulation ischemic stroke. We compared the methods of scoring collaterals on pre-tPA brain CT angiography for predicting functional outcomes in acute anterior circulation ischemic stroke. MATERIALS AND METHODS: Two hundred consecutive patients with acute anterior circulation ischemic stroke treated with IV-tPA during 2010-2012 were included. Two independent neuroradiologists evaluated intracranial collaterals by using the Miteff system, Maas system, the modified Tan scale, and the Alberta Stroke Program Early CT Score 20-point methodology. Good and extremely poor outcomes at 3 months were defined by modified Rankin Scale scores of 0-1 and 5-6 points, respectively. RESULTS: Factors associated with good outcome on univariable analysis were younger age, female sex, hypertension, diabetes mellitus, atrial fibrillation, small infarct core (ASPECTS ≥8), vessel recanalization, lower pre-tPA NIHSS scores, and good collaterals according to Tan methodology, ASPECTS methodology, and Miteff methodology. On multivariable logistic regression, only lower NIHSS scores (OR, 1.186 per point; 95% CI, 1.079-1.302; P = .001), recanalization (OR, 5.599; 95% CI, 1.560-20.010; P = .008), and good collaterals by the Miteff method (OR, 3.341; 95% CI, 1.203-5.099; P = .014) were independent predictors of good outcome. Poor collaterals by the Miteff system (OR, 2.592; 95% CI, 1.113-6.038; P = .027), Maas system (OR, 2.580; 95% CI, 1.075-6.187; P = .034), and ASPECTS method ≤5 points (OR, 2.685; 95% CI, 1.156-6.237; P = .022) were independent predictors of extremely poor outcomes. CONCLUSIONS: Only the Miteff scoring system for intracranial collaterals is reliable for predicting favorable outcome in thrombolyzed acute anterior circulation ischemic stroke. However, poor outcomes can be predicted by most of the existing methods of scoring intracranial collaterals.

Retinal vascular fractal dimension is associated with cognitive dysfunction.

Fractal analysis is a method used to quantify the geometric branching complexity and density of retinal vessels. This study examined the relationship of retinal vascular fractal dimension and other retinal vascular parameters with cognitive dysfunction in an older Asian population. Subjects aged 60 years and older from the Singapore Malay Eye Study were selected for analysis. Retinal vascular fractal dimension (Df) and other quantitative retinal vascular parameters (branching angle, tortuosity, and caliber) were measured based on a standardized grading protocol from photographs of the retinal fundus using a computer-assisted program. Qualitative retinal signs were also assessed from photographs. Cognitive dysfunction was defined as a locally validated Abbreviated Mental Test (AMT) score ≤6/10 in participants with 0-6 years of formal education and an AMT score ≤8/10 in those with more than 6 years of formal education. Cognitive dysfunction was identified in 262 of the 1202 participants (21.8%). Decreased retinal vascular Df was significantly associated with lower AMT score (P = .019). In multivariate logistic regression analysis, participants with lower retinal vascular Df values were more likely to have cognitive dysfunction (odds ratio, 1.71; 95% confidence interval, 1.03-2.82, comparing the lowest and highest Df quintiles). In subgroup analysis stratified for cardiovascular risk factors, this association was present in participants with hypertension and current smokers. Other retinal vascular signs were not associated with cognitive dysfunction. Decreased retinal vascular Df is associated with cognitive dysfunction in older persons. Rarefaction of the retinal vasculature may reflect similar changes in the cerebral microvasculature that may contribute to cognitive deterioration.

Chinese medicine NeuroAiD efficacy stroke recovery-extension study (CHIMES-E study): an observational multicenter study to investigate the longer-term efficacy of NeuroAiD in stroke recovery.

BACKGROUND: Stroke carries a poor long-term prognosis for death and disability. There are few acute treatments that reduce death and disability after stroke. The ongoing international, multicenter, randomized, placebo-controlled, double-blind CHIMES trial is currently testing the hypothesis that a 3-month course of the traditional Chinese medicine MLC601 (NeuroAiD) is superior to placebo in reducing neurological deficit and improving functional outcome after acute ischemic stroke in patients receiving standard stroke care. This extension study tests the hypothesis that at 2 years, an initial 3-month administration of NeuroAiD is superior to placebo in reducing neurological deficit and improving functional outcome in patients with cerebral infarction of an intermediate range of severity. METHODS: Study subjects will be those who are already participants in CHIMES - aged above 21 years, had signs and symptoms of acute stroke, 6 ≤ NIHSS ≤ 14, neuroimaging consistent with ischemic stroke, and received study medication within 72 h of stroke onset. A subject will not be eligible for inclusion in CHIMES-E if they have withdrawn consent from all participation and follow-up for CHIMES. Subjects will be contacted at 6, 12, 18 and 24 months after CHIMES enrollment. After verbal consent is obtained, subjects will be assessed for functional state by the modified Rankin scale (mRS) and Barthel Index (BI), and a history of recurrent vascular events as well as medical events. The primary outcome measure will be the mRS at month 24. Secondary outcome measures will be mRS and BI at 6, 12 and 18 months, and BI at 24 months. Analysis will be based on the intention-to-treat principle. If the number of patients lost to follow-up is substantial, a sensitivity analysis based on the last observation carried forward method will be carried out, to compare the results with those from the main analysis without imputation. Based on a cumulative odds ratio of 1.5 for the NeuroAiD group, a two-sided test of 5% type I error and an expected 30% dropout rate after 2 years of follow-up for the 1,100 patients recruited into CHIMES, the 770 subjects with mRS data expected to be available at year 2 yields an 89% power to detect a difference in efficacy between NeuroAiD and placebo. CONCLUSIONS: This study will provide evidence for the longer-term efficacy of an initial course of a neurorestorative therapy after acute ischemic stroke of intermediate severity.

CHIMES-I: sub-group analyzes of the effects of NeuroAiD according to baseline brain imaging characteristics among patients randomized in the CHIMES study.

RATIONALE: The clinical effects of neuroprotective and/or neurorestorative therapies may vary according to location and size of the ischemic injury. Imaging techniques can be useful in stratifying patients for trials that may be beneficial against particular ischemic lesion characteristics. AIM: To test the hypothesis that the efficacy of NeuroAiD compared with placebo in improving functional outcome and reducing neurological deficit in patients with cerebral infarction of intermediate severity varies between sub-groups of patients randomized in the main Chinese Medicine Neuroaid Efficacy on Stroke study when categorized according to baseline imaging characteristics. DESIGN: This is a retrospective cohort sub-group analysis of patients who participated in the main Chinese Medicine Neuroaid Efficacy on Stroke study, a multicenter, double-blind, placebo-controlled trial that recruited 1100 patients within 72 h of ischemic stroke onset with National Institutes of Health Stroke Scale 6-14 and were randomized to either NeuroAiD or placebo taken four capsules three times daily for three months. Review of the baseline images to classify the acute stroke lesions in terms of size, location, and extent of involvement will be performed retrospectively by two readers who will remain blinded as to treatment allocation and outcomes of the subjects. STUDY OUTCOMES: The primary efficacy end-point in the main Chinese Medicine Neuroaid Efficacy on Stroke study is the modified Rankin Scale grades at three-months. Secondary efficacy end-points are the National Institutes of Health Stroke Scale score at three-months; difference of National Institutes of Health Stroke Scale scores between baseline and 10 days and between baseline and three-months; difference of National Institutes of Health Stroke Scale sub-scores between baseline and 10 days and between baseline and three-months; modified Rankin Scale at 10 days, one-month, and three-months; Barthel index at three-months; and Mini Mental State Examination at 10 days and three-months. Analysis of these primary and secondary end-points will be performed for sub-groups defined in this study after review of the baseline brain imaging: nonlacunar and lacunar, cortical and sub-cortical, hemispheric vs. brainstem, Alberta Stroke Program Early CT score <7 and 7-10, and score <8 and 8-10.

Epidemiology of dementia in Asia: insights on prevalence, trends and novel risk factors.

Asia is the most populous region in the world and its rapidly growing societies are the sources of global development. However, accompanying this rapid growth is aging of the population with increasing occurrence of diseases, of which dementia is the most prominent, which provide major challenges to healthcare systems. Dementia prevalence in Asia has previously been found to be lower than Western populations, but recent studies show that age-specific prevalence rates are similar globally. Overall dementia prevalence is expected to rise dramatically across Asia due to maturing populations. Earlier Asian studies reported a lower prevalence of Alzheimer's disease (AD) and a higher prevalence of vascular dementia (VaD). Recent studies, however, show a reversal of this ratio that now parallels that of Western countries. This change may be attributed to an altered demographic profile, urbanization, environmental reactions, ethnicity and advances in the use of neuroimaging modalities. Several factors may influence the results of epidemiological studies including changes in societal perception of aging, family attitudes, validity of assessment tools due to language and literacy, and medical practitioners' expertise in recognizing dementia. Nevertheless, epidemiological studies in Asia may reveal factors contributory to inter-ethnic differences in dementia. Potentially modifiable risk factors apparent only in low and middle-income countries and gene-environment interactions may underlie these disparities and identification of such factors may lead to effective treatments.

Persistence of hyperdense middle cerebral artery sign on follow-up CT scan after intravenous thrombolysis is associated with poor outcome.

BACKGROUND: The rates and extent of recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA) remain highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment unenhanced computerized tomography (CT) of the brain represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome at 3 months. However, HMCAS is reliable only in AIS patients managed conservatively. In patients treated with systemic thrombolysis, HMCAS may disappear (representing clot dissolution) or persist (persisting clot) on the follow-up CT scan of the brain. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up CT scan of the brain can predict the final outcome at 3 months. METHODS: Data from consecutive AIS patients treated with IV-tPA, in a standardized protocol, from January 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation stroke was excluded. HMCAS was assessed on admission as well as follow-up CT by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by the modified Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0-1) and poor (mRS score 2-6). The data were analyzed for the early predictors of poor functional outcome with SPSS version 19 for Windows. RESULTS: Of the total of 2,238 patients admitted during the study period, 226 (11%) with anterior circulation AIS treated with intravenous thrombolysis were included. Median age of the patients was 65 years (range 19-92), 63% were males and they had a median National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4-32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1-point increase = 1.241; 95% CI = 1.151-1.337, p < 0.0005), lesser change in NIHSS score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666-0.800, p < 0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991-11.333, p = 0.039) were associated with poor outcome at 3 months. CONCLUSION: Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic stroke patients treated with IV-tPA can be used as an early predictor of poor functional outcome.

Usefulness of CT angiography for therapeutic decision making in thrombolyzing intubated patients with suspected basilar artery thrombosis.

BACKGROUND AND AIMS: Acute ischemic stroke (AIS) due to basilar artery thrombosis (BAT) causes high mortality and severe disability. Early neurological assessment and timely thrombolysis might improve outcome. BAT is difficult to diagnose due to wide spectrum of presentation and decreased conscious level. Emergency physicians often intubate BAT patients with airway compromise before arrival of stroke neurologist. We evaluated role of computerized tomography (CT) angiography (CTA) of brain and cervical arteries in early diagnosis of acute BAT in intubated patients and facilitating decision for thrombolysis. METHODS: Consecutive AIS patients presenting between 2007 and 2009 within 6 hours of symptom onset, with sudden deterioration in conscious level and intubation before assessment by neurologist, were included. All patients underwent brain CT and CTA. Outcomes were assessed at 3 months. RESULTS: Thrombolytic therapy, mainly intravenous tissue plasminogen activator (IV-TPA), was administered to 161 (8.4%) of 1,917 AIS patients during the study period. Acute BAT contributed 10.9% of our cohort. CTA was performed in 152 (94.4%) patients and the rest were excluded due to their impaired renal functions. Five patients (3 males, mean age 72 years) presenting with acute obtundation and airway compromise were intubated, sedated, and paralyzed before assessment by neurologist. CTA showed BAT in all. IV-TPA was initiated at 213 ± 59 minutes in 4 patients while 1 received intraarterial thrombolysis at 13 hours. There was no intracranial hemorrhage. Mean length of hospital stay was 11.8 days. Despite severe stroke at presentation, good functional recovery at 3 months (modified Rankin scale [mRS] 1) occurred in 2 patients; mRS 4 in 1, and 2 died. CONCLUSION: In patients with BAT, intubated before assessment by neurologist, CTA might help in confirming the diagnosis and facilitating therapeutic decision making for initiating thrombolysis.