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BACKGROUND: We present a rare case of NeuroBehcet's-related intracranial hypertension without cerebral venous thrombosis (NBrIHwCVT), occurring as the first presentation of NeuroBehcet's. In addition, we describe the novel use of subcutaneous tocilizumab for this indication. This is followed by a review of the literature on this topic. CASE: The patient was a 28-year-old lady of Southern Chinese origin with a known history of Behcet's disease with oral ulcers and ocular findings for which she was on mycophenolate mofetil and adalimumab. She presented with a headache and bilateral disc swelling associated with an intracranial pressure (ICP) of > 40cmH20. There were no structural lesions or cerebral venous thrombosis (CVT) on imaging. Initial lumbar puncture had raised leucocytes and protein. We discuss diagnostic challenges given persistently elevated ICP despite subsequent non-inflammatory cerebrospinal fluid (CSF) profiles and non-response to acetazolamide. She eventually showed a response to immunosuppressant therapy in the form of pulsed methylprednisolone, cyclophosphamide and subsequently subcutaneous tocilizumab, supporting the diagnosis of NBrIHwCVT. Complete normalization of ICP remains challenging. Her disease course was severe, unusual for her ethnicity. LITERATURE REVIEW: We identified 34 patients (including ours) from 14 publications. We found that the majority of NBrIHwCVT patients were young (average age of 34 years), with a slight female preponderance. Of the 17 cases in the literature with available data on CSF profile, none had raised leucocytes whilst one patient had elevated protein. Patients were generally treated with steroids and occasionally azathioprine, in line with the suspected autoimmune pathophysiology. Of 22 patients with data on outcome, six (27%) were noted to have recurrence of symptoms generally occurring a few months later. CONCLUSION: As demonstrated by this case, NBrIHwCVT can present with BD with raised ICP even if there is no prior history of NB, central Asian ethnicity, cerebral venous thrombosis or features of inflammation on the CSF. We demonstrated how novel use of Tocilizumab may have a role in the management of NBrIHwCVT. Based on our literature review, patients were more likely to be young, female, display a non-inflammatory CSF picture, be treated with steroids and harbour a possibility of recurrence.
Subject(s)
Behcet Syndrome , Intracranial Hypertension , Humans , Female , Adult , Behcet Syndrome/complications , Behcet Syndrome/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Immunosuppressive Agents/therapeutic useABSTRACT
OBJECTIVE: There is a paucity of studies investigating the outcomes among Asian stroke patients. Identifying subgroups of stroke patients at risk of poorer outcomes could identify patients who would benefit from targeted interventions. Therefore, the aim of this study was to identify which ischemic stroke patients at high risk of recurrent events and mortality. METHODS: This cohort study adhered to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines. We obtained data from the Singapore Stroke Registry (SSR) from 2005 to 2016 and cross referenced to the Death Registry and the Myocardial Infarction Registry. Outcome measures included recurrent stroke, acute myocardial infarction (AMI), and all-cause and stroke-related deaths. Multivariable Cox proportional hazards regression models were performed to determine risk factors for recurrent stroke, AMI, and all-cause and stroke-related deaths. RESULTS: A total of 64,915 patients (6705 young, and 58,210 older) were included in our analysis. Older stroke patients were found to have an increased risk of recurrent stroke (hazard ratio (HR) = 1.21, 95% confidence interval (CI) = 1.12-1.30), AMI (HR = 1.73, 95% CI = 1.54-1.95), all-cause death (HR = 2.49, 95% CI = 2.34-2.64), and stroke-related death (HR = 176, 95% CI = 1.61-1.92). Among young stroke patients, males were at increased risk for recurrent stroke (HR = 1.18, 95% CI = 1.01-1.39) and AMI (HR = 1.41, 95% CI = 1.08-1.83), but at reduced risk for all-cause (HR = 0.78, 95% CI = 0.69-0.89) and stroke-related deaths (HR = 0.79, 95% CI = 0.67-0.94). Ethnicity appeared to influence outcomes, with Malay patients at increased risk of recurrent stroke (HR = 1.37, 95% CI = 1.14-1.65), AMI (HR = 2.45, 95% CI = 1.87-3.22), and all-cause (HR = 1.43, 95% CI = 1.24-1.66) and stroke-related deaths (HR = 1.34, 95% CI = 1.09-1.64). Indian patients were also at increased risk of AMI (HR = 1.96, 95% CI = 1.41-2.72). Similar findings were seen among the older stroke patients. CONCLUSION: This study found that older stroke patients are at risk of poorer outcomes. Within the young stroke population specifically, males were predisposed to recurrent stroke and AMI but were protected against all-cause and stroke-related deaths. Males were also at reduced risk of all-cause and stroke-related deaths in the older stroke population. In addition, Malay and Indian patients experience poorer outcomes after first stroke. Further optimization of risk factors targeting these high-priority populations are needed to achieve high-quality care.
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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.
Subject(s)
Cognition , Cognitive Dysfunction , Humans , Male , Female , Aged , Middle Aged , Singapore/epidemiology , Risk Factors , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Cognitive Dysfunction/epidemiology , Time Factors , Memory , Risk Assessment , Prognosis , Ischemic Stroke/diagnosis , Ischemic Stroke/epidemiology , Neuropsychological Tests , Attention , Stroke/diagnosis , Stroke/complications , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/psychologyABSTRACT
INTRODUCTION: Reporting of sex and gender analysis in medical research has been shown to improve quality of the science and ensures findings are applicable to women and men. There is conflicting evidence on whether efforts by funding agencies and medical journals to encourage reporting of sex and gender analysis has resulted in tangible improvements. This study mapped the inclusion of sex and gender analysis in stroke and dementia research conducted in the Asia-Pacific region. METHODS: A systematic search for Asia-Pacific stroke and dementia research was conducted in PubMed and papers included from the period 2012 to 2022. Eligible studies were reviewed for inclusion of a primary sex or gender focus and categorized by type of sex and gender analysis. Author gender was determined using an algorithm and its associations with inclusion of sex and gender analysis examined. RESULTS: Total Asia-Pacific publications increased from 109 in 2012 to 313 in 2022, but the rate of studies with a primary sex or gender focus did not increase significantly (R2 = 0.06, F(1,9) = 0.59, p = 0.46). Australia, China, India, Japan and South Korea produced the most publications over the study period and were the only countries with at least 50 publications. The impact of author gender was mixed, with female first authorship associated with inclusion of sex or gender analysis and last female authorship associated with studies having a primary sex or gender focus. CONCLUSIONS: In the Asia-Pacific, brain health research is currently centered around high income countries and efforts are needed to ensure research findings are applicable through out the region. While there was a general increase in brain health publications over the last decade, the rate of sex and gender analysis was unchanged. This demonstrates that even with efforts in some countries in place, there is currently a lack of progress in the Asia-Pacific region to produce more research focusing on sex and gender analysis.
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OBJECTIVES: Recurrent strokes are associated with greater disability and mortality than first-time strokes. However, adherence to secondary stroke prevention medications has been reported to be suboptimal. We assessed medication adherence to antihypertensives, antiplatelets, and statins after acute ischemic stroke and identified factors associated with non-adherence behavior to each drug class. METHODS: This single center study is an extension of a larger prospective cohort study of ischemic stroke patients assessed at an outpatient post stroke clinic. Medication adherence behavior and medication knowledge was determined by direct questioning, and perceptions towards medications via the Beliefs about Medicines Questionnaire. Factors associated with non-adherence in each drug class were determined using logistic regression. RESULTS: Rates of adherence differed between antihypertensives (77.9%), antiplatelets (80.3%), and statins (64.7%) (p < 0.001) amongst the 193 patients surveyed. Non-adherence to antihypertensives was associated with living alone, taking < 5 medications, and stronger beliefs that medications are harmful. For antiplatelets, non-diabetic patients and patients with stronger beliefs that medications are harmful were more likely to be non-adherent. Patients non-adherent to statins were more likely to have a longer time since ischemic event and have a transient ischemic attack as the index event. CONCLUSIONS: Overall, medication adherence behavior to secondary stroke prevention medications was poor, with statins the least adhered to. Factors associated with non-adherence to each drug class could guide the development of tailored interventions to improve adherence to secondary stroke prevention medications.
Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors , Ischemic Stroke , Stroke , Humans , Antihypertensive Agents/adverse effects , Ischemic Stroke/drug therapy , Singapore/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Prospective Studies , Stroke/diagnosis , Stroke/drug therapy , Stroke/prevention & control , Secondary PreventionABSTRACT
BACKGROUND AND AIMS: Stroke is the second leading cause of death and third leading cause of disability worldwide. There is an increasing incidence of stroke among the young. In this study, we aimed to identify factors associated with poor long-term prognosis in young stroke patients. METHODS: In this longitudinal observational study, we recruited 147 young ischemic stroke patients within one week of ischemic stroke and followed them up for functional outcome (modified Rankin score (mRS)), recurrent vascular events, and recurrent hospitalisation. Poor function was labelled as mRS score of 3 and above. We performed univariate and multivariable logistic regression analyses to determine factors associated with poor long term functional outcome. RESULTS: At a median follow-up of 7-years, 32 (22%) of the 147 patients had poor functional outcome. In multivariable analyses, diabetes mellitus (OR = 9.01, CI 3.15 to 26.92), was the only independent predictor of poor function. In analyses stratified by diabetic status, recurrent vascular events (OR = 4.47, CI 1.40 to 14.28) were associated with poor functional outcome within young diabetic patients but not in non-diabetic patients. CONCLUSIONS: Our findings suggest that diabetes mellitus affects long-term functional outcome in young ischemic stroke and that its effect is mediated partly by recurrent vascular events. DATA ACCESS STATEMENT: Data obtained from Multi-Centre Retinal study (MCRS), Singapore site. Data cannot be made publicly available due to potentially identifiable research participant information.
Subject(s)
Diabetes Mellitus , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/epidemiology , Prognosis , Risk Factors , Stroke/epidemiology , Stroke/complications , Diabetes Mellitus/epidemiologyABSTRACT
BACKGROUND: Patients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolized into its active form by the CYP2C19 enzyme. Patients with loss of function (LOF) mutations in CYP2C19 are at risk for poorer secondary outcomes when prescribed clopidogrel. AIMS: We aimed to determine the cost-effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population. METHODS: Markov models were developed to look at the cost-effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype-guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature, and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: Empiric treatment with aspirin and ticagrelor was the most cost-effective treatment. Genotype-guided therapy was more cost-effective than empiric aspirin and clopidogrel if the LOF was above 48%. Empiric ticagrelor and aspirin was cost saving when compared to genotype-guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar. CONCLUSION: This study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype-guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 48%.
Subject(s)
Ischemic Attack, Transient , Ischemic Stroke , Stroke , Humans , Ticagrelor/therapeutic use , Aspirin/therapeutic use , Stroke/drug therapy , Stroke/prevention & control , Platelet Aggregation Inhibitors/therapeutic use , Clopidogrel/therapeutic use , Ischemic Attack, Transient/drug therapy , Ischemic Attack, Transient/prevention & control , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/therapeutic use , Cost-Benefit Analysis , Ischemic Stroke/drug therapy , Treatment Outcome , Drug Therapy, CombinationABSTRACT
INTRODUCTION: Patients with cancer are known to have an increased risk of ischemic stroke (IS) around the time of their diagnosis. However, there is a paucity of data in Asian populations, and as such, we aimed to determine cancer incidence rates and patterns in Asian IS patients as well as investigate the differences in vascular risk profile of IS patients with and without concomitant cancer. METHODS: We conducted a retrospective cross-sectional study using data from the Singapore Stroke and Cancer registries. We defined cases as patients with IS and a cancer diagnosis 2 years before or after the index IS. Cancer incidence was determined using the same direct age-standardization method performed for the Singapore general population in the 2015 Singapore cancer report. Multivariable logistic regression was used to analyze differences in vascular risk factors. RESULTS: Among 21,068 IS patients (mean age, 67.9 ± 13.3 years), 6.3% (1,330) were found to have concomitant cancer; 4.4% (935) had prior cancer while 1.8% (395) had cancer diagnoses within 2 years following IS. The cancer incidence among IS patients was 3,393 (95% confidence interval [CI], 1,937-4,849) per 100,000 person-years compared to 219-231 per 100,000 person-years in the general population. Older age (odds ratio [OR], 1.02 [95% CI, 1.01-1.02] per year), males (OR, 1.25 [95% CI, 1.11-1.41), Chinese ethnicity (OR, 1.61 [95% CI, 1.37-1.89]) and a lower prevalence of hypertension (OR, 0.84 [95% CI, 0.73-0.97)]), and hyperlipidemia (OR, 0.53 [95% CI, 0.45-0.62]) were independently associated with cancer-related IS. CONCLUSIONS: The age-standardized cancer incidence was 15 times higher in IS patients than the general population. IS patients with concomitant cancer were older and had a lower prevalence of vascular risk factors.
Subject(s)
Ischemic Stroke , Neoplasms , Stroke , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Cross-Sectional Studies , Retrospective Studies , Neoplasms/diagnosis , Neoplasms/epidemiology , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Cholesterol , Registries , IncidenceABSTRACT
Background and Objectives: Clopidogrel is an antiplatelet used in both primary and secondary prevention of cardiovascular diseases. It is a prodrug, requiring CYP2C19 for its metabolism to the active metabolite. The ABCD-GENE score, combining clinical attributes (age, body mass index, chronic kidney disease, diabetes mellitus), with genetic information (presence of 1 or 2 loss of function (LOF) alleles in the CYP2C19 gene) has been shown to identify patients with higher risk of recurrent cardiovascular events in high-risk populations undergoing percutaneous coronary intervention. We aimed to determine if the ABCD-GENE score or LOF alleles were associated with an increased risk of vascular events among clopidogrel users in a general population. Methods: We conducted a population based cohort study with UK Biobank's primary care prescription records to identify clopidogrel users. ABCD-GENE scores were calculated with closest available data from the first date of clopidogrel prescription. The number of LOF alleles present, and the clinical component ABCD, were separate exposures. The outcome of interest was a composite endpoint of vascular events comprised of myocardial infarction, ischemic stroke, and death due to either of these. We performed Cox proportional hazards models with clopidogrel as a time varying exposure to predict hazards of these outcomes. In order to determine the drug specificity of these exposures, the analyses were repeated in aspirin users, and in non-users of either aspirin or clopidogrel. Results: Among 11,248 clopidogrel users, 3,365 (30%) developed a vascular event over a mean follow-up of 5.95±3.94 years. ABCD-GENE score ≥10 was associated with an increased risk of vascular events (HR 1.13, 95% CI 1.03-1.23). In aspirin users, and in non-users of either aspirin or clopidogrel, the ABCD-GENE score was also associated with increased risk of vascular events. In clopidogrel users, aspirin users, and non-users of either drug, the ABCD score was associated with increased risk of vascular events. The presence of two CYP2C19 LOF alleles was associated with an increased risk of vascular events in aspirin and non-users but not in clopidogrel users. Discussion: In this population-based cohort study, the ABCD-GENE score was associated with an increased risk of vascular events in clopidogrel users, aspirin users, and in non-users of either drug. The clinical component, ABCD was also associated with an increased risk of vascular events in all three groups. This suggests that the ABCD-GENE score is not specific to clopidogrel users in identifying persons at high risk of vascular events in a general sample with low baseline CYP2C19 LOF allele frequency.
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BACKGROUND: Sleep disordered breathing (SDB) is an under-recognised independent risk factor and a potential consequence of stroke. We systematically reviewed and meta-analysed the effectiveness of positive airway pressure (PAP) therapy in improving post-stroke outcomes. METHODS: We searched CENTRAL, Embase, PubMed, CINAHL, PsycINFO, Scopus, ProQuest, Web of Science and CNKI (China National Knowledge Infrastructure) for randomised controlled trials comparing PAP therapy against a control or placebo group. We evaluated the pooled effects of PAP therapy on recurrent vascular events, neurological deficit, cognition, functional independence, daytime sleepiness and depression using random effects meta-analyses. RESULTS: We identified 24 studies. Our meta-analyses showed that PAP therapy reduced recurrent vascular events (risk ratio 0.47, 95% CI 0.28-0.78), and showed significant beneficial effects on neurological deficit (Hedges' g= -0.79, 95% CI -1.19- -0.39), cognition (g=0.85, 95% CI 0.04-1.65), functional independence (g=0.45, 95% CI 0.01-0.88) and daytime sleepiness (g= -0.96, 95% CI -1.56- -0.37). However, there was insignificant reduction in depression (g= -0.56, 95% CI -2.15-1.02). No publication bias was detected. CONCLUSIONS: Post-stroke patients with SDB benefited from PAP therapy. Prospective trials are needed to determine the ideal initiation period and the minimum effective therapeutic dose.
Subject(s)
Disorders of Excessive Somnolence , Sleep Apnea Syndromes , Humans , Continuous Positive Airway Pressure/adverse effects , Prospective Studies , Risk Factors , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/therapyABSTRACT
BACKGROUND AND PURPOSE: Self-management programs enhance survival in stroke patients. However, they require patient-centered designs to be effective. The aim of this study was therefore to investigate the type of post-stroke self-management programs that appeal to stroke survivors, and to estimate their willingness to participate in such programs. METHODS: A Discrete Choice Experiment was administered to patients who had either a transient ischemic attack (TIA) or stroke within the past 3 years and were cognitively intact (i.e., stroke survivors). Stroke survivors were presented with eight choice tasks and asked to choose between 'No Program' and two hypothetical post-stroke management programs that varied by six attributes: Topics covered by the program; schedule of the program; frequency and duration of the sessions; number of participants; out-of-pocket registration fee for the whole program; and rewards for completing the program. RESULTS: The analysis involved 146 stroke survivors. Based on the mixed logit model, the predicted willingness to participate ranged from 53% to 76%. The most popular characteristics in a program were topics on health education and risk management, being scheduled during weekends as four sessions that are each 2 hours long and involve four participants, a registration fee of SGD50 (â¼USD36), and SGD500 (â¼USD359) reward for program completion. CONCLUSIONS: Interest in post-stroke self-management programs was high, with at least half of the sample showing interest in participating in these programs. Program features such as focusing on health education and risk management, charging a low registration fee, and offering incentives helped to increase the demand.
Subject(s)
Ischemic Attack, Transient , Self-Management , Stroke Rehabilitation , Stroke , Humans , Stroke/diagnosis , Stroke/therapy , Ischemic Attack, Transient/diagnosis , Ischemic Attack, Transient/therapy , SurvivorsABSTRACT
BACKGROUND AND PURPOSE: A third of stroke patients suffer from post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. B-vitamin supplementation provides a possible safe and affordable treatment to mitigate post-stroke neuropsychiatric sequelae via reducing homocysteine levels. Our study aims to examine the effect of B-vitamin supplementation in the prevention of post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. Our secondary aims were to investigate associations between baseline factors and the three outcomes. METHODS: Patients were recruited as part of a Singaporean substudy of a randomized controlled trial that examined the effect of B-vitamin supplementation on recurrent cardiovascular events. Cognitive decline, depressive symptoms, and anxiety symptoms were assessed with neuropsychological assessments and Hospital Anxiety and Depression Scale 6 monthly. Cox regression analyses were performed to determine treatment efficacy. Logistic regression used to examine factors associated with cognitive decline, depressive symptoms, and anxiety symptoms. RESULTS: A total of 707 were included in the analyses. Survival and hazards ratio analysis showed no treatment effect of B-vitamins on cognitive decline, depressive symptoms, and anxiety symptoms. Cognitive decline was only associated with age. Depressive symptoms were associated with large anterior cerebral infarcts and hyperlipidemia. CONCLUSIONS: Our study showed no benefit of supplementation with B-vitamins for post-stroke cognitive decline, depressive symptoms, or anxiety symptoms. Depressive symptoms were associated with larger anterior cerebral infarcts, which may be reflective of the disability associated with larger infarcts.
Subject(s)
Cognition Disorders , Stroke , Vitamin B Complex , Humans , Vitamin B Complex/therapeutic use , Vitamin B Complex/pharmacology , Cognition Disorders/prevention & control , Stroke/complications , Cognition , Dietary Supplements , Cerebral InfarctionABSTRACT
Introduction: The National Institutes of Health Stroke Scale (NIHSS), originally designed in the United States of America, contains items on dysphasia and dysarthria that are deemed culturally unsuitable for the Singapore context. We compared the error rates of dysphasia objects, dysphasia phrases and dysarthria words between the original and alternative items in a cohort of Singaporean subjects without dysphasia or dysarthria. Methods: In this prospective study, 140 English-speaking Singaporean subjects without impairments of dysphasia or dysarthria had an assessment of NIHSS items 9 and 10 using the original and alternative items. Paired analyses were conducted for comparison of error rates. Results: The error rates were high for four original dysphasia objects (Hammock: 62.9%, Cactus: 38.6%, Feather: 23.6%, Glove: 20.7%) and significantly lower for alternative items (Snail: 5%, Horse: 1.4%, Hanger: 1.4%, Car: 0%) (P < 0.001). For dysphasia phrases and dysarthria words, the error rates were low and there were no differences in error rates between the original and alternative items. Conclusion: There are cultural issues with several dysphasia objects in the original NIHSS as evidenced by the high error rates, which were lowered with more culturally suitable alternatives. This study formed a basis to derive a more suitable version of the NIHSS for English-speaking subjects in Singapore.
Subject(s)
Aphasia , Stroke , Humans , United States , Animals , Horses , Stroke/diagnosis , Singapore , Dysarthria/diagnosis , Prospective Studies , National Institutes of Health (U.S.) , Aphasia/diagnosis , Severity of Illness IndexABSTRACT
Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an in vivo vascular injury model of restenosis. Furthermore, we studied the effects of caffeine in primary human and mouse aortic VSMCs and immortalized mouse aortic VSMCs. Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells. Genetic deletion of the key autophagy gene Atg5, and the Sqstm1/p62 gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy. Interestingly, caffeine also decreased WNT-signaling and the expression of two WNT target genes, Axin2 and Ccnd1 (cyclin D1). This effect was mediated by autophagic degradation of a key member of the WNT signaling cascade, DVL2, by caffeine to decrease WNT signaling and cell proliferation. SQSTM1/p62, MAP1LC3B-II and DVL2 were also shown to interact with each other, and the overexpression of DVL2 counteracted the inhibition of cell proliferation by caffeine. Taken together, our in vivo and in vitro findings demonstrated that caffeine reduced VSMC proliferation by inhibiting WNT signaling via stimulation of autophagy, thus reducing the vascular restenosis. Our findings suggest that caffeine and other autophagy-inducing drugs may represent novel cardiovascular therapeutic tools to protect against restenosis after angioplasty and/or stent placement.
Subject(s)
Autophagy , Muscle, Smooth, Vascular , Animals , Autophagy/physiology , Caffeine/metabolism , Caffeine/pharmacology , Cell Proliferation , Cells, Cultured , Humans , Mice , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Sequestosome-1 Protein/metabolism , Wnt Signaling PathwayABSTRACT
INTRODUCTION: Diabetes mellitus (DM) is known to influence outcomes in the short term following stroke. However, the impact of DM on long-term functional outcomes after stroke is unclear. We compared functional outcomes periodically over 7 years between diabetic and nondiabetic ischemic stroke patients, and investigated the impact of DM on the long-term trajectory of post-stroke functional outcomes. We also studied the influence of age on the diabetes-functional outcome association. METHODS: This is a longitudinal observational cohort study of 802 acute ischemic stroke patients admitted to the Singapore General Hospital from 2005 to 2007. Functional outcomes were assessed using the modified Rankin Scale (mRS) with poor functional outcome defined as mRS ≥3. Follow-up data were determined at 6 months and at median follow-up durations of 29 and 86 months. RESULTS: Among the 802 ischemic stroke patients studied (mean age 64 ± 12 years, male 63%), 42% had DM. In regression analyses adjusting for covariates, diabetic patients were more likely to have poor functional outcomes at 6 months (OR = 2.12, 95% CI: 1.23-3.67) and at median follow-up durations of 29 months (OR = 1.96, 95% CI: 1.37-2.81) and 86 months (OR = 2.27, 95% CI: 1.58-3.25). In addition, age modulated the effect of DM, with younger stroke patients (≤65 years) more likely to have long-term poor functional outcome at the 29-month (p = 0.0179) and 86-month (p = 0.0144) time points. CONCLUSIONS: DM was associated with poor functional outcomes following ischemic stroke in the long term, with the effect remaining consistent throughout the 7-year follow-up period. Age modified the effect of DM in the long term, with an observed increase in risk in the ≤65 age-group but not in the >65 age-group.
Subject(s)
Brain Ischemia , Diabetes Mellitus , Ischemic Stroke , Stroke , Aged , Brain Ischemia/diagnosis , Brain Ischemia/therapy , Diabetes Mellitus/diagnosis , Humans , Ischemic Stroke/diagnosis , Ischemic Stroke/therapy , Male , Middle Aged , Risk Factors , Singapore/epidemiology , Stroke/diagnosis , Stroke/therapyABSTRACT
PURPOSE: This systematic review and meta-analysis aims to synthesise the evidence of the effectiveness of self-management interventions with action-taking components in improving self-efficacy, health-related quality of life, basic and instrumental activities of daily living, and depression for adult stroke survivors. MATERIALS AND METHODS: Nine electronic databases were searched for relevant studies, including grey literature and ongoing studies. Randomised controlled trials targeting adult stroke survivors comparing health-related outcomes of patients receiving self-management interventions with action-taking components to usual care, placebo, or no-treatment were included. Screening, data extraction, and methodological quality assessment were conducted by two reviewers. Meta-analyses were performed. Overall quality of evidence was assessed using the GRADE tool. RESULTS: A total of seventeen studies were included. Meta-analyses showed that the intervention may result in a slight increase in self-efficacy (SMD = 0.29, 95% CI [0.07-0.52], p = 0.010, I2 = 47%) and basic activities of daily living (SMD = 0.31, 95% CI [0.16-0.46], p < 0.001, I2 = 0%), but not for the other outcomes. CONCLUSIONS: Self-management interventions with action-taking components may result in a slight improvement in self-efficacy and rehabilitation of basic activities of daily living. Future research should investigate which core self-management skill, or combination of them, is most effective in improving short-term and long-term outcomes.IMPLICATIONS FOR REHABILITATIONStroke can be a chronic condition as approximately half of stroke survivors suffer from permanent disabilities.Self-management interventions are one form of rehabilitation programmes available to stroke survivors.Self-management interventions with action-taking components may result in a slight increase in patient self-efficacy and carrying out basic activities of daily living compared to usual care given.
Subject(s)
Self-Management , Stroke Rehabilitation , Stroke , Humans , Adult , Activities of Daily Living , Quality of Life , SurvivorsABSTRACT
OBJECTIVE: To determine if rehabilitation uptake and adherence can be increased by providing coordinated transportation (increased convenience) and eliminating out-of-pocket costs (reduced expense). DESIGN: Three-arm randomized controlled trial. SETTING: Stroke units of 2 Singapore tertiary hospitals. PARTICIPANTS: Singaporeans or permanent residents 21 years or older who were diagnosed as having stroke and were discharged home with physician's recommendation to continue outpatient rehabilitation (N=266). INTERVENTIONS: A Transportation Incentives arm (T), which provides free transportation services, a Transportation & Sessions Incentives arm (T&S), offering free transportation and prescribed stroke rehabilitation sessions, and a control arm, Education (E), consisting of a stroke rehabilitation educational program. MAIN OUTCOME MEASURES: The primary study outcome was uptake of outpatient rehabilitation services (ORS) among patients poststroke and key predefined secondary outcomes being number of sessions attended and adherence to prescribed sessions. RESULTS: Uptake rate of ORS was 73.0% for E (confidence interval [CI], 63.8%-82.3%), 81.8% for T (CI, 73.8%-89.8%), and 84.3% for T&S (CI, 76.7%-91.8%). Differences of T and T&S vs E were not statistically significant (P=.22 and P=.10, respectively). However, average number of rehabilitation sessions attended were significantly higher in both intervention arms: 5.50±7.65 for T and 7.51±9.52 for T&S vs 3.26±4.22 for control arm (E) (T vs E: P=.017; T&S vs E: P<.001). Kaplan-Meier analysis indicated that persistence was higher for T&S compared with E (P=.029). CONCLUSIONS: This study has demonstrated a possibility in increasing the uptake of and persistence to stroke ORS with free transportation and sessions. Incentivizing survivors of stroke to take up ORS is a new strategy worthy of further exploration for future policy change in financing ORS or other long-term care services.
Subject(s)
Patient Compliance , Stroke Rehabilitation/economics , Stroke Rehabilitation/methods , Transportation/economics , Aged , Ambulatory Care , Female , Humans , Male , Middle Aged , MotivationABSTRACT
OBJECTIVE: To investigate the relationship between medication adherence, trust in physician and beliefs about medication among stroke survivors. To determine whether beliefs about medication would mediate the relationship between trust in physician and medication adherence. METHODS: A sample of 200 patients with a diagnosis of ischemic stroke or transient ischemic attack (TIA) completed a one-time survey, including the shortened Medication Adherence Report Scale (MARS-5), Beliefs about Medicines Questionnaire (BMQ), and Trust in Physician Scale (TIPS). RESULTS: Our study found that medication adherence was associated with trust in physician (p = 0.019) and four factors of beliefs about medication (BMQ1-Necessity: p < 0.001; BMQ2-Concerns: p = 0.024; BMQ3-Overuse: p = 0.016; BMQ4-Harm: p < 0.001). Furthermore, we found monthly income of survivors moderated the relationship between trust in physician and medication adherence (p = 0.007, CI(95%): [-0.822, -0.132]). CONCLUSIONS: The beliefs about medication mediating the relationship between trust in physician and medication adherence were different based on the stroke survivors' income bracket. PRACTICE IMPLICATIONS: Interventions being developed to improve medication adherence may benefit from improving stroke survivors' trust in physician and addressing their beliefs about medication. In addition, healthcare providers are advised to take monthly income into consideration to effectively address stroke survivors' concerns regarding prescribed medications to mitigate stroke recurrence.
Subject(s)
Physicians , Stroke , Health Knowledge, Attitudes, Practice , Humans , Medication Adherence , Stroke/drug therapy , Surveys and Questionnaires , TrustABSTRACT
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.