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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. [ABSTRACT FROM AUTHOR]

Background: Stroke patients have increased risks of falls. We examined national registry data to evaluate the association between post-stroke functional level and the risk of low falls among post-stroke patients.Methods: This retrospective cohort study analyzed data from national registries to examine the risk factors for post-stroke falls. Data for patients who suffered ischemic strokes and survived the index hospital admission was obtained from the Singapore National Stroke Registry and matched to the National Trauma Registry, from 2011 to 2015. The primary outcome measure was a low fall (fall height ≤ 0.5 m). Competing risk analysis was performed to examine the association between functional level (by modified Rankin score [mRS] at discharge) and the risk of subsequent low falls.Results: In all, 2255 patients who suffered ischemic strokes had recorded mRS. The mean age was 66.6 years and 58.5% were men. By the end of 2015, 54 (2.39%) had a low fall while 93 (4.12%) died. After adjusting for potential confounders, mRS was associated with fall risk with an inverted U-shaped relationship. Compared to patients with a score of zero, the sub-distribution hazard ratio (SHR) increased to a maximum of 3.42 (95%CI:1.21-9.65, p = 0.020) for patients with a score of 2. The SHR then declined to 2.45 (95%CI:0.85-7.12, p = 0.098), 2.86 (95%CI:0.95-8.61, p = 0.062) and 1.93 (95%CI:0.44-8.52, p = 0.38) for patients with scores of 3, 4 and 5 respectively.Conclusions: An inverted U-shaped relationship between functional status and fall risk was observed. This is consistent with the complex interplay between decreasing mobility (hence decreased opportunity to fall) and increasing susceptibility to falls. Fall prevention intervention could be targeted accordingly. (263 words). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Purpose: MLC601 has been shown in preclinical studies to enhance neurorestorative mechanisms after stroke. The aim of this post hoc analysis was to assess whether combining MLC601 and rehabilitation has an effect on improving functional outcomes after stroke. Methods: Data from the CHInese Medicine NeuroAiD Efficacy on Stroke (CHIMES) and CHIMES-Extension (CHIMES-E) studies were analyzed. CHIMES-E was a 24-month follow-up study of subjects included in CHIMES, a multi-centre, double-blind placebo-controlled trial which randomized subjects with acute ischemic stroke, to either MLC601 or placebo for 3 months in addition to standard stroke treatment and rehabilitation. Subjects were stratified according to whether they received or did not receive persistent rehabilitation up to month (M)3 (non- randomized allocation) and by treatment group. The modified Rankin Scale (mRS) and Barthel Index were assessed at month (M) 3, M6, M12, M18, and M24. Results: Of 880 subjects in CHIMES-E, data on rehabilitation at M3 were available in 807 (91.7%, mean age 61.8 ± 11.3 years, 36% female). After adjusting for prognostic factors of poor outcome (age, sex, pre-stroke mRS, baseline National Institute of Health Stroke Scale, and stroke onset-to-study-treatment time), subjects who received persistent rehabilitation showed consistently higher treatment effect in favor of MLC601 for all time points on mRS 0–1 dichotomy analysis (ORs 1.85 at M3, 2.18 at M6, 2.42 at M12, 1.94 at M18, 1.87 at M24), mRS ordinal analysis (ORs 1.37 at M3, 1.40 at M6, 1.53 at M12, 1.50 at M18, 1.38 at M24), and BI ≥95 dichotomy analysis (ORs 1.39 at M3, 1.95 at M6, 1.56 at M12, 1.56 at M18, 1.46 at M24) compared to those who did not receive persistent rehabilitation. Conclusions: More subjects on MLC601 improved to functional independence compared to placebo among subjects receiving persistent rehabilitation up to M3. The larger treatment effect of MLC601 was sustained over 2 years which supports the hypothesis that MLC601 combined with rehabilitation might have beneficial and sustained effects on neuro-repair processes after stroke. There is a need for more data on the effect of combining rehabilitation programs with stroke recovery treatments. [ABSTRACT FROM AUTHOR]

Background: The Chinese Medicine NeuroAiD Efficacy on Stroke recovery - Extension (CHIMES-E) study is among the few acute stroke trials with long-term outcome data. We aimed to evaluate the recovery pattern and the influence of prognostic factors on treatment effect of MLC601 over 2 years. Methods: The CHIMES-E study evaluated the 2 years outcome of subjects aged ≥ 18 years with acute ischemic stroke, National Institutes of Health Stroke Scale (NIHSS) score 6-14, pre-stroke modified Rankin Scale (mRS) score ≤ 1 included in a multicenter, randomized, double-blind, placebo- controlled trial of MLC601 for 3 months. Standard stroke care and rehabilitation were allowed during follow-up with mRS score being assessed in-person at month (M) 3 and by telephone at M1, M6, M12, M18 and M24. Results: Data from 880 subjects were analyzed. There was no difference in baseline characteristics between treatment groups. The proportion of subjects with mRS score 0-1 increased over time in favor of MLC601 most notably from M3 to M6, thereafter remaining stable up to M24, while the proportion deteriorating to mRS score ≥ 2 remained low at all time points. Older age (p < 0.01), female sex (p = 0.06), higher baseline NIHSS score (p < 0.01) and longer onset to treatment time (OTT; p < 0.01) were found to be predictors of poorer outcome at M3. Greater treatment effect, with more subjects improving on MLC601 than placebo, was seen among subjects with 2 or more prognostic factors (OR 1.65 at M3, 1.78 at M6, 1.90 at M12, 1.65 at M18, 1.39 at M24), especially in subjects with more severe stroke or longer OTT. Conclusions: The sustained benefits of MLC601 over 2 years were due to more subjects improving to functional independence at M6 and beyond compared to placebo. Selection of subjects with poorer prognosis, particularly those with more severe NIHSS score and longer OTT delay, as well as a long follow-up period, may improve the power of future trials investigating the treatment effect of neuroprotective or neurorestorative therapies. [ABSTRACT FROM AUTHOR]

Background: The CHInese Medicine NeuroAiD Efficacy on Stroke recovery (CHIMES) study was an international randomized double-blind placebo-controlled trial of MLC601 (NeuroAiD) in subjects with cerebral infarction of intermediate severity within 72 h. CHIMES-E (Extension) aimed at evaluating the effects of the initial 3-month treatment with MLC601 on long-term outcome for up to 2 years. Methods: All subjects randomized in CHIMES were eligible for CHIMES-E. Inclusion criteria for CHIMES were age ≥18, baseline National Institute of Health Stroke Scale of 6-14, and pre-stroke modified Rankin Scale (mRS) ≤1. Initial CHIMES treatment allocation blinding was maintained, although no further study treatment was provided in CHIMES-E. Subjects received standard care and rehabilitation as prescribed by the treating physician. mRS, Barthel Index (BI), and occurrence of medical events were ascertained at months 6, 12, 18, and 24. The primary outcome was mRS at 24 months. Secondary outcomes were mRS and BI at other time points. Results: CHIMES-E included 880 subjects (mean age 61.8 ± 11.3; 36% women). Adjusted OR for mRS ordinal analysis was 1.08 (95% CI 0.85-1.37, p = 0.543) and mRS dichotomy ≤1 was 1.29 (95% CI 0.96-1.74, p = 0.093) at 24 months. However, the treatment effect was significantly in favor of MLC601 for mRS dichotomy ≤1 at 6 months (OR 1.49, 95% CI 1.11-2.01, p = 0.008), 12 months (OR 1.41, 95% CI 1.05-1.90, p = 0.023), and 18 months (OR 1.36, 95% CI 1.01-1.83, p = 0.045), and for BI dichotomy ≥95 at 6 months (OR 1.55, 95% CI 1.14-2.10, p = 0.005) but not at other time points. Subgroup analyses showed no treatment heterogeneity. Rates of death and occurrence of vascular and other medical events were similar between groups. Conclusions: While the benefits of a 3-month treatment with MLC601 did not reach statistical significance for the primary endpoint at 2 years, the odds of functional independence defined as mRS ≤1 was significantly increased at 6 months and persisted up to 18 months after a stroke. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Previous clinical trials have shown that Neuroaid® (MLC601), a traditional Chinese medicine, shows good tolerability and superiority over another traditional Chinese medicine in terms of neurological disability and functional outcome and thus may be beneficial as part of a poststroke rehabilitation program. The safety of MLC601 on hemostasis, hematology and biochemistry has been established in normal subjects and patients with nonacute stroke over a short treatment period. We assessed the safety of Neuroaid in patients with acute stroke treated for 3 months in a substudy of an ongoing randomized placebo-controlled trial. Methods: Laboratory tests (biochemical, hematological and electrocardiogram) were conducted at the month 3 follow-up, in addition to baseline tests. A total of 114 patients were recruited. As there were 13 dropouts, a total of 52 patients on MLC601 and 49 on placebo were available for analysis. Serious adverse events (SAEs) were also analyzed. Results: There were no statistically or clinically significant differences between treatment groups in biochemical, hematological or electrocardiogram tests at month 3, nor any statistically or clinically significant differences in the absolute and relative changes of the various parameters between baseline and 3 months. SAEs were similar and were those commonly seen in stroke patients. Conclusions: Longer-term laboratory safety data show no differences between MLC601 and placebo, confirming the safety of MLC601 in acute stroke patients receiving a 3-month treatment. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Rationale Because of its rapidly-growing and aging populations, the global burden of stroke will be felt most strongly in Asia. Data from Asia are scarce. Even rarer are data from multiethnic populations. Aim The Singapore Stroke Registry is a countrywide registry of risk factors, stroke subtypes, management and outcome of incident and recurrent stroke in multiethnic Singapore. Methods and design Using a cold-pursuit design, potential subjects are identified from medical claims, hospital discharge summaries and death certificates. Standardized methods are used for case ascertainment and data recording by trained staff into standardized case report forms. All ages and both genders are included. Study outcome Stroke incidence, subtypes and mortality will be calculated. Trend data will be obtained. Inter-ethnic differences will be explored. Discussion The Registry has many features of an 'ideal' incidence study. Previously unavailable countrywide data on an Asian population will be acquired. The unique data on inter-ethnic differences will help fill knowledge gaps in stroke epidemiology. [ABSTRACT FROM AUTHOR]

Background: Informal caregiving is an integral part of post-stroke recovery with strenuous caregiving demands often resulting in caregiving burden, threatening sustainability of caregiving and potentially impacting stroke survivor's outcomes. Our study aimed to examine and quantify objective and subjective informal care burden after stroke; and to explore the factors associated with informal care burden in Singapore.Methods: Stroke patients and their informal caregivers were recruited from all five tertiary hospitals in Singapore from December 2010 to September 2013. Informal care comprised of assistance provided by informal caregivers with any of the activities of daily living. Informal care burden was measured by patients' likelihood of requiring informal care, hours of informal care required, and informal caregivers' Zarit's Burden Score. We examined informal care burden at 3-months and 12-months post-stroke. Generalized linear regressions were applied with control variables including patients' and informal caregivers' demographic characteristics, arrangement of informal care, and patients' health status including stroke severity (measured using National Institute of Health Stroke Scale), functional status (measured using Modified Rankin Scale), self-reported depression, and common comorbidities.Results: Three hundred and five patients and 263 patients were examined at 3-months and 12-months. Around 35% were female and 60% were Chinese. Sixty three percent and 49% of the patients required informal care at 3-months and 12-months point, respectively. Among those who required informal care, average hours required per week were 64.3 h at 3-months and 76.6 h at 12-months point. Patients with higher functional dependency were more likely to require informal care at both time points, and required more hours of informal care at 3-months point. Female informal caregivers and those caring for patients with higher functional dependency reported higher Zarit's Burden. While informal caregivers who worked full-time reported higher burden, those caring for married stroke patients reported lower burden at 3-months point. Informal caregivers who co-cared with foreign domestic workers, i.e.: stay-in migrant female waged domestic workers, reported lower burden.Conclusions: Informal care burden remains high up to 12-months post-stroke. Factors such as functional dependency, stroke severity, informal caregiver gender and co-caring with foreign domestic workers were associated with informal care burden. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 β = - 0.111; 12-month standardized β = - 0.109) and mRS (3-month standardized β = - 0.122; 12-month standardized β = - 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]