Incidence and Outcomes of Cardiocerebral Infarction: A Cohort Study of 2 National Population-Based Registries.

BACKGROUND: Cardiocerebral infarction (CCI), which is concomitant with acute myocardial infarction (AMI) and acute ischemic stroke (AIS), is a rare but severe presentation. However, there are few data on CCI, and the treatment options are uncertain. We investigated the characteristics and outcomes of CCI compared with AMI or AIS alone. METHODS: We performed a retrospective cohort study of 120 531 patients with AMI and AIS from the national stroke and AMI registries in Singapore. Patients were categorized into AMI only, AIS only, synchronous CCI (same-day), and metachronous CCI (within 1 week). The primary outcome was all-cause mortality, and the secondary outcome was cardiovascular mortality. The mortality risks were compared using Cox regression. Multivariable models were adjusted for baseline demographics, clinical variables, and treatment for AMI or AIS. RESULTS: Of 127 919 patients identified, 120 531 (94.2%) were included; 74 219 (61.6%) patients had AMI only, 44 721 (37.1%) had AIS only, 625 (0.5%) had synchronous CCI, and 966 (0.8%) had metachronous CCI. The mean age was 67.7 (SD, 14.0) years. Synchronous and metachronous CCI had a higher risk of 30-day mortality (synchronous: adjusted HR [aHR], 2.41 [95% CI, 1.77-3.28]; metachronous: aHR, 2.80 [95% CI, 2.11-3.73]) than AMI only and AIS only (synchronous: aHR, 2.90 [95% CI, 1.87-4.51]; metachronous: aHR, 4.36 [95% CI, 3.03-6.27]). The risk of cardiovascular mortality was higher in synchronous and metachronous CCI than AMI (synchronous: aHR, 3.03 [95% CI, 2.15-4.28]; metachronous: aHR, 3.41 [95% CI, 2.50-4.65]) or AIS only (synchronous: aHR, 2.58 [95% CI, 1.52-4.36]; metachronous: aHR, 4.52 [95% CI, 2.95-6.92]). In synchronous CCI, AMI was less likely to be managed with PCI and secondary prevention medications (P<0.001) compared with AMI only. CONCLUSIONS: Synchronous CCI occurred in 1 in 200 cases of AIS and AMI. Synchronous and metachronous CCI had higher mortality than AMI or AIS alone.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Remote online open book examinations: through the lenses of faculty and students in health professions programmes.

BACKGROUND: Open book examinations have been used to assess students' higher order cognitive skills. These examinations can be conducted online remotely with the advancement of technology. However, there are concerns regarding its validity and reliability particularly if the examinations are not proctored. The objective of this study was to explore the perceptions of faculty and students in health professions programmes about remote online open book examinations (ROOBE). METHODS: Semi-structured interviews were conducted among 22 faculty staff who were involved in ROOBE in health professions programmes. All interviews were audio recorded, transcribed verbatim and analysed using a thematic analysis approach. The perceptions of 249 medical students were obtained using an online questionnaire after they completed ROOBE. RESULTS: The faculty agreed that open book examinations could promote students' higher order cognitive skills and reduce students' stress. However, they were concerned about students' academic integrity during non-invigilated ROOBE which could affect recognition by accreditation and professional bodies. The shift from traditional practice of closed-book examinations to ROOBE required change management with the support of guidelines and faculty training.  Majority of the students claimed that the examinations were challenging as they assessed their ability to apply knowledge in real world problems. Nevertheless, they preferred ROOBE due to less anxiety and memorisation, and more emphasis on problem solving skills. The shortcomings were insufficient time for information searching during examinations and uncertainty in preparedness for future practice as they focused less on memorisation of factual knowledge during examination preparation. Cheating among peers and internet instability during non-invigilated ROOBE were the concerns highlighted by some students. CONCLUSIONS: Faculty and students expressed favourable views about ROOBE in promoting higher order cognitive skills. Adequate technological support was essential during ROOBE. While there was a need to address issues related to academic integrity, ROOBE could be included as an authentic assessment within the systems of assessment.

Four Discrete Silver Iodobismuthates/Bromobismuthates with Metal Complexes: Syntheses, Structures, Photocurrent Responses, and Theoretical Studies.

Using in situ formed metal complexes of [Fe(bipy)3]2+ or [Ni(bipy)3]2+ (bipy = 2,2'-bipyridine) as templates, four new Ag-Bi-X (X = I and Br) compounds are first isolated in the metal-complex-decorated heterometallic halobismuthate family, namely [M(bipy)3]AgBiI6 (M = Fe (1), Ni (2)), [Fe(bipy)3]AgBiBr6 (3), and [Ni(bipy)3]AgBiBr6 (4). Compounds 1-4 feature discrete [AgBiX6]n2n- anions, exhibiting three polymorphisms that may be ascribed to the different stackings and the flexible condensations of [BiX6] octahedrons and [AgX4] tetrahedra/[AgX3] triangles. UV-vis diffuse reflectance analyses reveal that they are narrow band gap semiconductor materials (ca. 1.82-2.13 eV). Intriguingly, the title compounds display excellent photoelectrical switching properties, with photocurrent density following the order 3 > 4 > 2 > 1. In addition, the comparative studies of intermolecular interactions, theoretical band structures, density of states, and effective masses of three polymorphisms have also been investigated.

Burden of informal care in stroke survivors and its determinants: a prospective observational study in an Asian setting.

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.

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.

Medical students' orientation toward lifelong learning in an outcome-based curriculum and the lessons learnt.

BACKGROUND: Lifelong learning (LL) is an important outcome of medical training. The objective of this study is to measure the orientation of medical students toward LL and to determine the types of self-directed learning (SDL) activities that contribute toward LL skills. METHODS: The Jefferson Scale of Physician Lifelong Learning for medical student (JeffSPLL-MS) questionnaire was used. Factor analysis was performed, Cronbach's alpha and effect size were calculated. The types of learning activities that contribute to LL skills were identified. RESULTS: Three-factor structure emerged from the factor analysis and were identified as learning beliefs and motivation, skills in seeking information and attention to learning opportunities. A significant increase (p < .05; ES = 0.27) in orientation toward LL with academic progression was observed. Clinical students improved significantly in the domains of 'skills in seeking information' (p < .001; ES = 0.48) and 'attention to learning opportunities' (p < .001; ES = 0.55). Problem-based learning, flipped classroom, guided reading, projects and experiential learning activities are perceived to be effective for promoting LL. CONCLUSIONS: Medical students' LL skills develop progressively from preclinical to clinical years. Self-directed learning activities are perceived to be effective in promoting LL skills.

Student evaluation of the learning environment in an undergraduate pharmacy programme: Lessons for educators.

BACKGROUND: Student evaluation of the learning environment is important to enhance learning experiences. Programs such as Pharmacy use feedback from the evaluation to identify teaching-learning issues and use it to improve the quality of the learning experiences. The article aims to explore the general observations from the evaluation; to identify how the feedback is used to improve the learning environment and to identify lessons for educators in managing and using the feedback. METHODS: A cross-sectional data analysis of Pharmacy students' learning environment from 2011-2015 based on data from module, faculty, IMU-REEM and Student Barometer Survey was applied. Feedback obtained from the data was triangulated to establish commonalities/differences of the issues. RESULTS: Based on the analysis, issues affecting Pharmacy student learning experiences were identified. The identified issues included teaching by subject matter experts, pedagogical delivery and physical learning environment. Seven lessons were presented for educators to assess the practicality of the feedback. CONCLUSIONS: The feedback serves as a means to improve the Pharmacy program. Nonetheless, the challenges lie between the ideal and realistic expectations of students in optimizing the learning experiences. Lessons acquired from the evaluation of the learning environment are essential for educators in managing and using the information.

Twelve tips for institutional approach to outcome-based education in health professions programmes.

Outcome-based education (OBE) has brought along a significant development in health professions education in the past decade. The shift from a process-driven to product-driven model of education is valuable for ensuring graduate quality and facilitating global movement of healthcare workers. Such a model can align the expectations of key stakeholders in an era of rapid knowledge expansion and technological advancement. Nevertheless, the experienced benefits of OBE depend on the effectiveness of its implementation. This article therefore provides practical tips and strategies for implementing OBE in order to maximize its potential.

[Acute cerebral ischemia-induced down-regulation of Sirt3 protein expression contributes to neuronal injury via damaging mitochondrial function].

This study was aimed to determine the effect of acute cerebral ischemia on the protein expression level of silent mating type information regulator 2 homolog 3 (Sirt3) in the neurons and clarify the pathological role of Sirt3 in acute cerebral ischemia. The mice with middle cerebral artery occlusion (MCAO) and primary cultured rat hippocampal neurons with oxygen glucose deprivation (OGD) were used as acute cerebral ischemia models in vivo and in vitro, respectively. Sirt3 overexpression was induced in rat hippocampal neurons by lentivirus transfection. Western blot was utilized to measure the changes in Sirt3 protein expression level. CCK8 assay was used to detect cell viability. Immunofluorescent staining was used to detect mitochondrial function. Transmission electron microscope was used to detect mitochondrial autophagy. The results showed that, compared with the normoxia group, hippocampal neurons from OGD1 h/reoxygenation 2 h (R2 h) and OGD1 h/R12 h groups exhibited down-regulated Sirt3 protein expression levels. Compared with contralateral normal brain tissue, the ipsilateral penumbra region from MCAO1 h/reperfusion 24 h (R24 h) and MCAO1 h/R72 h groups exhibited down-regulated Sirt3 protein expression levels, while there was no significant difference between the Sirt3 protein levels on both sides of sham group. OGD1 h/R12 h treatment damaged mitochondrial function, activated mitochondrial autophagy and reduced cell viability in hippocampal neurons, whereas Sirt3 over-expression attenuated the above damage effects of OGD1 h/R12 h treatment. These results suggest that acute cerebral ischemia results in a decrease in Sirt3 protein level. Sirt3 overexpression can alleviate acute cerebral ischemia-induced neural injuries by improving the mitochondrial function. The current study sheds light on a novel strategy against neural injuries caused by acute cerebral ischemia.

Comparison of the roles of estrogens and androgens in breast cancer and prostate cancer.

Breast cancer (BC) and prostate cancer (PC) are the second most common malignant tumors in women and men in western countries, respectively. The risks of death are 14% for BC and 9% for PC. Abnormal estrogen and androgen levels are related to carcinogenesis of the breast and prostate. Estradiol stimulates cancer development in BC. The effect of estrogen on PC is concentration-dependent, and estrogen can regulate androgen production, further affecting PC. Estrogen can also increase the risk of androgen-induced PC. Androgen has dual effects on BC via different metabolic pathways, and the role of the androgen receptor (AR) in BC also depends on cell subtype and downstream target genes. Androgen and AR can stimulate both primary PC and castration-resistant PC. Understanding the mechanisms of the effects of estrogen and androgen on BC and PC may help us to improve curative BC and PC treatment strategies.

Financial toxicity and its associations with health-related quality of life among urologic cancer patients in an upper middle-income country.

PURPOSE: This study examined the prevalence of financial toxicity (FT) and associated factors among urologic cancer patients. The association between FT and health-related quality of life (HRQoL) was also investigated. METHODS: A total of 429 respondents diagnosed with urologic cancers (prostate cancer, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed using a structured questionnaire. Objective and subjective FT were measured by catastrophic health expenditure (healthcare-cost-to-income ratio greater than 40%) and the Personal Financial Well-being Scale, respectively. HRQoL was measured with the Functional Assessment of Cancer Therapy - General 7 Items scale. RESULTS: Objective and subjective FT were experienced by 16.1 and 47.3% of the respondents, respectively. Respondents who sought treatment at a private hospital and had out-of-pocket health expenditures were more likely to experience objective FT, after adjustment for covariates. Respondents who were female and had a monthly household income less than MYR 5000 were more likely to experience average to high subjective FT. Greater objective FT (OR = 2.75, 95% CI 1.09-6.95) and subjective FT (OR = 4.68, 95% CI 2.63-8.30) were associated with poor HRQoL. CONCLUSIONS: The significant association between both objective and subjective FT and HRQoL highlights the importance of reducing FT among urologic cancer patients. Subjective FT was found to have a greater negative impact on HRQoL.

Self-perceived burden and its associations with health-related quality of life among urologic cancer patients.

OBJECTIVE: This study examined the prevalence of self-perceived burden (SPB) and its association with health-related quality of life (HRQoL) among urologic cancer patients. METHODS: This was a prospective, cross-sectional study. A total of 429 respondents diagnosed with urologic cancers (prostate, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed by using a structured questionnaire. SPB and HRQoL were measured by the Self-perceived Burden Scale and the Functional Assessment of Cancer Therapy-General 7 Item Scale respectively. RESULTS AND CONCLUSION: Self-perceived burden was experienced by 73.2% of the respondents. Respondents who had a lower education level, a monthly household income

Sampling, extraction and incidence of redberry mites (Acalitus essigi) on blackberries in Australia.

'Redberry disease' on blackberries is hypothesised to be caused by the redberry mite (RBM), Acalitus essigi (Hassan), and results in uneven ripening of blackberry drupelets, which become bright red, hard and inedible. This damage has been reported to cause significant crop losses in commercial blackberry production in most regions where commercial blackberries are grown. However, RBM are difficult to detect and manage due to their tiny body size. In this study, a new 'shake and wash' extraction method has been developed, enabling faster, more accurate mite detection and quantification. The 'shake and wash' method extracted significantly more RBM and predatory mites (Phytoseiidae) than the previously recommended 'sticky tape' method, where mite extraction using this technique was increased by 53 and 60%, respectively. RBM counts were then made from the fruit of wild and commercial blackberry cultivars. Significantly higher RBM populations were isolated in cultivars 'BL454' (mean = 12.1 per fruit) and 'Chester' (mean = 2.6 per fruit) from several sites indicating potential RBM susceptibility in these cultivars. The highest levels of disease incidence and RBM numbers were observed on wild blackberry fruit. The redberry disease incidence increased from 13.5 to 44.9% as the mean population of RBM increased on wild fruit. Further methods were developed to extract mites from winter buds on canes. RBM numbers were lower in the fruit compared to winter buds. RBM detection is best achieved in winter buds rather than fruit and may be an important tool for RBM detection and subsequent management in the cropping season.

Management of advanced prostate cancer in a middle-income country: real-world consideration of the Advanced Prostate Cancer Consensus Conference 2017.

OBJECTIVE: To examine the results of the Malaysian Advanced Prostate Cancer Consensus Conference (MyAPCCC) 2018, held for assessing the generalizability of consensus reached at the Advanced Prostate Cancer Consensus Conference (APCCC 2017) to Malaysia, a middle-income country. METHODS: Six key sections were chosen: (1) high-risk localized and locally advanced prostate cancer, (2) oligometastatic prostate cancer, (3) castration-naïve prostate cancer, (4) castrate resistant prostate cancer, (5) use of osteoclast-targeted therapy and (6) global access to prostate cancer drugs. There were 101 consensus questions, consisting of 91 questions from APCCC 2017 and 10 new questions from MyAPCCC 2018, selected and modified by the steering committee; of which, 23 questions were assessed in both ideal world and real-world settings. A panel of 22 experts, comprising of 11 urologists and 11 oncologists, voted on 101 predefined questions anonymously. Final voting results were compared with the APCCC 2017 outcomes. RESULTS: Most voting results from the MyAPCCC 2018 were consistent with the APCCC 2017 outcomes. No consensus was achieved for controversial topics with little level I evidence, such as management of oligometastatic disease. No consensus was reached on using high-cost drugs in castration-naïve or castration-resistant metastatic prostate cancer in real-world settings. All panellists recommended using generic drugs when available. CONCLUSIONS: The MyAPCCC 2018 voting results reflect the management of advanced prostate cancer in a middle-income country in a real-world setting. These results may serve as a guide for local clinical practices and highlight the financial challenges in modern healthcare.

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.

Post-stroke patients with moderate function have the greatest risk of falls: a National Cohort Study.

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).

Effect of Combined Treatment with MLC601 (NeuroAiDTM) and Rehabilitation on Post-Stroke Recovery: The CHIMES and CHIMES-E Studies.

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.

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.