High Total Hospitalization Cost but Low Cost of Imaging Studies in Recurrent Acute Ischemic Stroke Patients

Background

Due to the high risk and severity of recurrence after stroke attack, recurrence is a major reason contributing to the disease burden. This study aims to determine whether recurrence is a significant contributor of hospitalization cost in items for ischemic stroke patients.

Methods

This study assessed acute ischemic stroke patients admitted to an academic medical center in 2003 through 2009. The t-test and Chi-square tests were used to compare first-ever and recurrent ischemic stroke groups in terms of total and categorized hospitalization cost, and multiple regression was performed to assess the influence of stroke recurrence.

Results

Recurrent ischemic strokes were associated with higher total cost, but examination cost showed no difference between the two groups. The recurrent stroke group showed higher laboratory but lower imaging cost. Of imaging studies, there was no significant difference in computed tomography scan cost while the first-ever stroke group spent more on magnetic resonance imaging and sonography. Controlling for other influential factors, recurrence was discovered to be a significant factor in lowering examination cost.

Conclusions

The findings of stroke recurrence in lowering examination cost could be explained from two perspectives, different clinical patterns of healthcare utilization and patients'' economic status in recurrent stroke.     

The Predictive Value of Waist-To-Height Ratio for Ischemic Stroke in a Population-Based Prospective Cohort Study among Mongolian Men in China

Objective

To explore the associations between waist-to-height ratio (WHtR), body mass index (BMI) and waist circumference (WC) and risk of ischemic stroke among Mongolian men in China.

Methods

A population-based prospective cohort study was conducted from June 2003 to July 2012 in Inner Mongolia, an autonomous region in north China. A total of 1034 men aged 20 years and older free of cardiovascular disease were included in the cohort and followed up for an average of 9.2 years. The subjects were divided into four groups by WHtR levels (WHtR<0.40, 0.40≤WHtR≤0.50, 0.50<WHtR≤0.60, WHtR>0.60). The cumulative survival rates of ischemic stroke among the four groups were estimated with the Kaplan-Meier curves and compared by log-rank test. Cox proportional hazards models and Receiver Operating Characteristic (ROC) curves were employed to evaluate the associations between obesity indices and ischemic stroke.

Results

A total of 47 ischemic stroke patients were observed during the follow-up period. The cumulative incidence and incidence density of ischemic stroke were 4.55% and 507.61/100 000 person-years, respectively. After the major risk factors were adjusted, individuals with WHtR>0.60 had a 3.56-fold increased risk of ischemic stroke compared with those with 0.40≤WHtR≤0.50. Hazard ratio (HR) and 95% confidence intervals (CI) of ischemic stroke for a 1-SD increase in WHtR was 1.34(95% CI: 1.00–1.81). After adding BMI or WC to models, higher WHtR remained significantly associated with increased risk of ischemic stroke. The Kaplan-Meier survival curves showed that the cumulative survival rate in the group with WHtR>0.60 was significantly lower than in the group with 0.40≤WHtR≤0.50 (log-rank test, P = 0.025). The areas under the curve for each index were as follows: 0.586 for WHtR, 0.543 for WC; 0.566 for BMI.

Conclusions

Higher WHtR is associated with risk of ischemic stroke in Mongolian males. WHtR may be useful in predicting ischemic stroke incidence in males.     

CT Permeability Imaging Predicts Clinical Outcomes in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolytic Therapy

In this study, we determined whether a prediction of final infarct volume (FIV) and clinical outcomes in patients with an acute stroke is improved by using a contrast transfer coefficient (K ^trans) as a biomarker for blood–brain barrier (BBB) dysfunction. Here, consecutive patients admitted with signs and symptoms suggesting acute hemispheric stroke were included in this study. Ninety-eight participants with intra-arterial therapy were assessed (46 female). Definition of predicted FIV was performed using conventional perfusion CT (PCT-PIV) parameters alone and in combination with K ^trans (K ^trans-PIV). Multiple logistic regression analyses and linear regression modeling were conducted to determine independent predictors of the 90-day modified Rankin score (mRS) and FIV, respectively. We found that patients with favorable outcomes were younger and had lower National Institutes of Health Stroke Scale (NIHSS) score, smaller PCT-PIV, K ^trans-PIV, and smaller FIV (P?<?0.001). K ^trans-PIV showed good correlation with FIV (P?<?00.001, R ²?=?0.6997). In the regression analyses, K ^trans-PIV was the best predictor of clinical outcomes (P?=?0.009, odds ratio (OR)?=?1.960) and also the best predictor for FIV (F?=?75.590, P?<?0.0001). In conclusion, combining PCT and K ^trans maps derived from first-pass PCT can identify at-risk cerebral ischemic tissue more precisely than perfusion parameters alone. This provides improved accuracy in predicting FIV and clinical outcomes.     

Characteristics of Misclassified CT Perfusion Ischemic Core in Patients with Acute Ischemic Stroke

Background

CT perfusion (CTP) is used to estimate the extent of ischemic core and penumbra in patients with acute ischemic stroke. CTP reliability, however, is limited. This study aims to identify regions misclassified as ischemic core on CTP, using infarct on follow-up noncontrast CT. We aim to assess differences in volumetric and perfusion characteristics in these regions compared to areas that ended up as infarct on follow-up.

Materials and Methods

This study included 35 patients with >100 mm brain coverage CTP. CTP processing was performed using Philips software (IntelliSpace 7.0). Final infarct was automatically segmented on follow-up noncontrast CT and used as reference. CTP and follow-up noncontrast CT image data were registered. This allowed classification of ischemic lesion agreement (core on CTP: rMTT≥145%, aCBV<2.0 ml/100g and infarct on follow-up noncontrast CT) and misclassified ischemic core (core on CTP, not identified on follow-up noncontrast CT) regions. False discovery ratio (FDR), defined as misclassified ischemic core volume divided by total CTP ischemic core volume, was calculated. Absolute and relative CTP parameters (CBV, CBF, and MTT) were calculated for both misclassified CTP ischemic core and ischemic lesion agreement regions and compared using paired rank-sum tests.

Results

Median total CTP ischemic core volume was 49.7ml (IQR:29.9ml-132ml); median misclassified ischemic core volume was 30.4ml (IQR:20.9ml-77.0ml). Median FDR between patients was 62% (IQR:49%-80%). Median relative mean transit time was 243% (IQR:198%-289%) and 342% (IQR:249%-432%) for misclassified and ischemic lesion agreement regions, respectively. Median absolute cerebral blood volume was 1.59 (IQR:1.43–1.79) ml/100g (P<0.01) and 1.38 (IQR:1.15–1.49) ml/100g (P<0.01) for misclassified ischemic core and ischemic lesion agreement, respectively. All CTP parameter values differed significantly.

Conclusion

For all patients a considerable region of the CTP ischemic core is misclassified. CTP parameters significantly differed between ischemic lesion agreement and misclassified CTP ischemic core, suggesting that CTP analysis may benefit from revisions.     

The Taxonomy Statistic Uncovers Novel Clinical Patterns in a Population of Ischemic Stroke Patients

In this paper, we describe a simple taxonomic approach for clinical data mining elaborated by Marczewski and Steinhaus (M-S), whose performance equals the advanced statistical methodology known as the expectation-maximization (E-M) algorithm. We tested these two methods on a cohort of ischemic stroke patients. The comparison of both methods revealed strong agreement. Direct agreement between M-S and E-M classifications reached 83%, while Cohen’s coefficient of agreement was κ = 0.766(P < 0.0001). The statistical analysis conducted and the outcomes obtained in this paper revealed novel clinical patterns in ischemic stroke patients. The aim of the study was to evaluate the clinical usefulness of Marczewski-Steinhaus’ taxonomic approach as a tool for the detection of novel patterns of data in ischemic stroke patients and the prediction of disease outcome. In terms of the identification of fairly frequent types of stroke patients using their age, National Institutes of Health Stroke Scale (NIHSS), and diabetes mellitus (DM) status, when dealing with rough characteristics of patients, four particular types of patients are recognized, which cannot be identified by means of routine clinical methods. Following the obtained taxonomical outcomes, the strong correlation between the health status at moment of admission to emergency department (ED) and the subsequent recovery of patients is established. Moreover, popularization and simplification of the ideas of advanced mathematicians may provide an unconventional explorative platform for clinical problems.     

Altered Resting-State fMRI Signals in Acute Stroke Patients with Ischemic Penumbra

Background

Identifying the ischemic penumbra in acute stroke subjects is important for the clinical decision making process. The aim of this study was to use resting-state functional magnetic resonance singal (fMRI) to investigate the change in the amplitude of low-frequency fluctuations (ALFF) of these subjects in three different subsections of acute stroke regions: the infarct core tissue, the penumbra tissue, and the normal brain tissue. Another aim of this study was to test the feasilbility of consistently detecting the penumbra region of the brain through ALFF analysis.

Methods

Sixteen subjects with first-ever acute ischemic stroke were scanned within 27 hours of the onset of stroke using magnetic resonance imaging. The core of infarct regions and penumbra regions were determined by diffusion and perfusion-weighted imaging respectively. The ALFF were measured from resting-state blood oxygen level dependent (BOLD) fMRI scans. The averaged relative ALFF value of each regions were correlated with the time after the onset of stroke.

Results

Relative ALFF values were significantly different in the infarct core tissue, penumbra tissue and normal brain tissue. The locations of lesions in the ALFF maps did not match perfectly with diffusion and perfusion-weighted imagings; however, these maps provide a contrast that can be used to differentiate between penumbra brain tissue and normal brain tissue. Significant correlations between time after stroke onset and the relative ALFF values were present in the penumbra tissue but not in the infarct core and normal brain tissue.

Conclusion

Preliminary results from this study suggest that the ALFF reflects the underlying neurovascular activity and has a great potential to estimate the brain tissue viability after ischemia. Results also show that the ALFF may contribute to acute stroke imaging for thrombolytic or neuroprotective therapies.     

Interactions among Candidate Genes Selected by Meta-Analyses Resulting in Higher Risk of Ischemic Stroke in a Chinese Population

Ischemic stroke (IS) is a multifactorial disorder caused by both genetic and environmental factors. The combined effects of multiple susceptibility genes might result in a higher risk for IS than a single gene. Therefore, we investigated whether interactions among multiple susceptibility genes were associated with an increased risk of IS by evaluating gene polymorphisms identified in previous meta-analyses, including methylenetetrahydrofolate reductase (MTHFR) C677T, beta fibrinogen (FGB, β-FG) A455G and T148C, apolipoprotein E (APOE) ε2–4, angiotensin-converting enzyme (ACE) insertion/deletion (I/D), and endothelial nitric oxide synthase (eNOS) G894T. In order to examine these interactions, 712 patients with IS and 774 controls in a Chinese Han population were genotyped using the SNaPshot method, and multifactor dimensionality reduction analysis was used to detect potential interactions among the candidate genes. The results of this study found that ACE I/D and β-FG T148C were significant synergistic contributors to IS. In particular, the ACE DD + β-FG 148CC, ACE DD + β-FG 148CT, and ACE ID + β-FG 148CC genotype combinations resulted in higher risk of IS. After adjusting for potential confounding IS risk factors (age, gender, family history of IS, hypertension history and history of diabetes mellitus) using a logistic analysis, a significant correlation between the genotype combinations and IS patients persisted (overall stroke: adjusted odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.22–2.02, P < 0.001, large artery atherosclerosis subtype: adjusted OR = 1.50, 95% CI: 1.08–2.07, P = 0.016, small-artery occlusion subtype: adjusted OR = 2.04, 95% CI: 1.43–2.91, P < 0.001). The results of this study indicate that the ACE I/D and β-FG T148C combination may result in significantly higher risk of IS in this Chinese population.     

VCTDSA联合CT灌注成像在急性缺血性卒中诊断运用探究

目的：探讨64层容积CT数字减影血管造影（Volume computed tomography digital subtraction angiography, VCTDSA）联合CT灌注成像在急性缺血性卒中诊断价值。方法：回顾性分析45例临床确诊为急性缺血性卒中患者的临床资料,分别给予VCTDSA与CT灌注成像处理,分析这两种技术对急性缺血性卒中患者的诊断敏感性和特异性。结果：45例患者检查有颅内有不同部位出血灶,多见于脑室,均伴有不同程度的异常血管网形成,其中VCTDSA图像质量优于CT灌注成像,VCTDSA较DSA可准确显示和测量动静脉瘘口大小,VCTDSA与MRA在瘤体长轴、瘤颈的比较中无显著性差异。结论：与其他减影CTA比较,VCTDSA联合CT灌注成像在急性缺血性卒中患者的诊断中具有优势。     

Evaluation of the Recognition of Stroke in the Emergency Room (ROSIER) Scale in Chinese Patients in Hong Kong

Background and Purpose

The objective of this study was to determine the performance of the Recognition Of Stroke In the Emergency Room (ROSIER) scale in risk-stratifying Chinese patients with suspected stroke in Hong Kong.

Methods

This was a prospective cohort study in an urban academic emergency department (ED) over a 7-month period. Patients over 18 years of age with suspected stroke were recruited between June 2011 and December 2011. ROSIER scale assessment was performed in the ED triage area. Logistic regression analysis was used to estimate the impacts of diagnostic variables, including ROSIER scale, past history and ED characteristics.

Findings

715 suspected stroke patients were recruited for assessment, of whom 371 (52%) had acute cerebrovascular disease (302 ischaemic strokes, 24 transient ischaemic attacks (TIA), 45 intracerebral haemorrhages), and 344 (48%) had other illnesses i.e. stroke mimics. Common stroke mimics were spinal neuropathy, dementia, labyrinthitis and sepsis. The suggested cut-off score of>0 for the ROSIER scale for stroke diagnosis gave a sensitivity of 87% (95%CI 83–90), a specificity of 41% (95%CI 36–47), a positive predictive value of 62% (95%CI 57–66), and a negative predictive value of 75% (95%CI 68–81), and the AUC was 0.723. The overall accuracy at cut off>0 was 65% i.e. (323+141)/715.

Interpretation

The ROSIER scale was not as effective at differentiating acute stroke from stroke mimics in Chinese patients in Hong Kong as it was in the original studies, primarily due to a much lower specificity. If the ROSIER scale is to be clinically useful in Chinese suspected stroke patients, it requires further refinement.     

miR-146a and miR-196a2 Polymorphisms in Patients with Ischemic Stroke in the Northern Chinese Han Population

MicroRNAs are endogenous non-coding RNAs about 22 nucleotides in length that can repress the expression of proteins by binding to the 3′-untranslated regions of target messenger RNAs. We hypothesized that polymorphisms in miR-146a and miR-196a2 are associated with risk of ischemic stroke in the northern Chinese Han population. In a case–control study of 368 ischemic stroke patients and 381 control subjects that were frequency matched by age and gender, we genotyped two single nucleotide polymorphisms (rs11614913 in miR-196a2 and rs2910164 in miR-146a) using polymerase chain reaction-ligation detection reaction. The frequencies of the rs2910164 CC genotype and C allele within miR-146a were not significantly different in patients with ischemic stroke compared with those in the healthy control group. In subgroup meta-analysis, rs2910164 in miR-146a and large-artery atherosclerosis, rather than small-vessel disease, showed the significant association under the dominant model (CC vs CG+GG, OR 1.694; 95 % CI 1.199–2.395 p = 0.003). After adjusting for confounding risk factors of ischemic stroke by logistic regression analysis, this significant correlation remained. In addition, the distributions of the miR-196a2 genotypes and alleles were not statistically different between ischemic stroke and healthy groups. We also did not find any significant association from stroke subtypes. The CC genotype and C allele of rs2910164 within miR-146a are associated with an increased incidence of large-artery athersclerotic stroke in the northern Chinese Han population. This study indicates that miR-146a (rs2910164) might contribute to ischemic stroke susceptibility in the northern Chinese Han population.     

Association of AHSG Gene Polymorphisms with Ischemic Stroke in a Han Chinese Population

Previous studies have shown associations of fetuin-A (alpha₂-Heremans-Schmid glycoprotein, AHSG) with various disorders, including insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and atherosclerosis. In this study, genotype and allele frequencies of the rs4918 SNP in the AHSG gene were examined in 380 patients with ischemic stroke and 350 healthy controls from a Northern Han Chinese population via the PCR-RFLP technique. Frequencies of the GG genotype and the G allele in AHSG (rs4918) were significantly higher in patients with ischemic stroke or atherosclerotic cerebral infarction than those in the control group (P < 0.05). Logistic regression analysis demonstrated the significance of rs4918 in these patients, after adjustment for confounding factors (P < 0.05). These findings suggest that rs4918 SNPs of the AHSG gene are associated with a risk for ischemic stroke in a Northern Han Chinese population.     

Anticoagulation for the Acute Management of Ischemic Stroke

Few prospective studies support the use of anticoagulation during the acute phase of ischemic stroke, though observational data suggest a role in certain populations. Depending on the mechanism of stroke, systemic anticoagulation may prevent recurrent cerebral infarction, but concomitantly carries a risk of hemorrhagic transformation. In this article, we describe a case where anticoagulation shows promise for ischemic stroke and review the evidence that has discredited its use in some circumstances while showing its potential in others.     

The Ischemic Stroke Genetics Study (ISGS) Protocol

Background  

The molecular basis for the genetic risk of ischemic stroke is likely to be multigenic and influenced by environmental factors. Several small case-control studies have suggested associations between ischemic stroke and polymorphisms of genes that code for coagulation cascade proteins and platelet receptors. Our aim is to investigate potential associations between hemostatic gene polymorphisms and ischemic stroke, with particular emphasis on detailed characterization of the phenotype.     

Association of the Genetic Polymorphisms in Pre-MicroRNAs with Risk of Ischemic Stroke in a Chinese Population

microRNA (miRNA) plays a role in the pathogenesis of ischemic stroke, and single nucleotide polymorphisms in miRNA genes may contribute to disease susceptibility. However, the effect of miR-146a, miR-196a2, and miR-499 polymorphisms on ischemic stroke susceptibility has been rarely reported. Using the TaqMan assay, we evaluated the association of hsa-miR-146a/rs2910164, hsa-miR-196a2/rs11614913, and hsa-miR-499/rs3746444 polymorphisms with the risk of ischemic stroke in a Chinese population with 531 ischemic stroke patients and 531 control subjects. Rs2910164 C/G genotypes were significantly associated with increased risk of ischemic stroke in different genetic model (homozygote comparison: OR = 2.00, 95% CI, 1.29–3.12, P = 0.002; additive model: OR = 1.35, 95% CI, 1.10–1.65, P = 0.004;dominant model: OR = 1.33, 95% CI, 1.00–1.75, P = 0.049; recessive model: OR = 1.82, 95% CI, 1.20–2.74, P = 0.004). Subjects with allele G of hsa-miR-146a/ rs2910164 also showed increased risk of ischemic stroke (OR = 1.33, 95% CI, 1.09–1.62, P = 0.005). Stratification analysis showed that the association between rs2910164 and the risk of ischemic stroke was more pronounced in subjects over 60 years old, females, non-drinkers, subjects without hypertension or diabetes mellitus. There were significant combined effects between miR-146a/rs2910164 and fasting glucose/low-density lipoprotein cholesterol levels on ischemic stroke susceptibility. However, we failed to find any association between the alleles/genotypes of rs11614913 T/C and ischemic stroke, respectively (P> 0.05). In summary, this study provides evidence that miR-146a/rs2910164 might be associated with a significantly increased risk of ischemic stroke in a Chinese population, and the combined effects between miRNA polymorphism and fasting glucose /blood lipid levels may contribute to stroke pathogenesis.     

Plasma D-Dimer Levels Are Associated with Stroke Subtypes and Infarction Volume in Patients with Acute Ischemic Stroke

Background

It has been suggested that modestly elevated circulating D-dimer values may be associated with acute ischemic stroke (AIS). Thus, the purpose of this study was to investigate the association between plasma D -dimer level at admission and AIS in Chinese population.

Methods

In a prospective observational study, plasma D-dimer levels were measured using a particle-enhanced, immunoturbidimetric assay on admission in 240 Chinese patients with AIS. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to D-dimer levels.

Results

Plasma median D-dimer levels were significantly (P = 0.000) higher in AIS patients as compared to healthy controls (0.88; interquartiler range [IQR], 0.28–2.11 mg/L and 0.31; IQR, 0.17–0.74 mg/L). D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score(r = 0.179, p = 0.005) and infarct volume(r = 0.425, p = 0.000). Those positive trends still existed even after correcting for possible confounding factors (P = 0.012, 0.000; respectively). Based on the Receiver operating characteristic (ROC) curve, the optimal cut-off value of plasma D-dimer levels as an indicator for diagnosis of cardioembolic strokes was projected to be 0.91 mg/L, which yielded a sensitivity of 83.7% and a specificity of 81.5%, the area under the curve was 0.862(95% confidence interval [CI], 0.811–0.912).

Conclusion

We had shown that plasma D-dimer levels increased with increasing severity of stroke as defined by the NIHSS score and infarct volume. These associations were independent other possible variables. In addition, cardioembolic strokes can be distinguished from other stroke etiologies by measuring plasma D-dimer levels very early (0–48hours from stroke symptom onset).     

Early Sitting in Ischemic Stroke Patients (SEVEL): A Randomized Controlled Trial

Background

Extended immobility has been associated with medical complications during hospitalization. However no clear recommendations are available for mobilization of ischemic stroke patients.

Objective

As early mobilization has been shown to be feasible and safe, we tested the hypothesis that early sitting could be beneficial to stroke patient outcome.

Methods

This prospective multicenter study tested two sitting procedures at the acute phase of ischemic stroke, in a randomized controlled fashion (clinicaltrials.org registration number {"type":"clinical-trial","attrs":{"text":"NCT01573299","term_id":"NCT01573299"}}NCT01573299). Patients were eligible if they were above 18 years of age and showed no sign of massive infarction or any contra-indication for sitting. In the early-sitting group, patients were seated out of bed at the earliest possible time but no later than one calendar day after stroke onset, whereas the progressively-sitting group was first seated out of bed on the third calendar day after stroke onset. Primary outcome measure was the proportion of patients with a modified Rankin score [0–2] at 3 months post stroke. Secondary outcome measures were a.) prevalence of medical complications, b.) length of hospital stay, and c.) tolerance to the procedure.

Results

One hundred sixty seven patients were included in the study, of which 29 were excluded after randomization. Data from 138 patients, 63 in the early-sitting group and 75 in the progressively-sitting group were analyzed. There was no difference regarding outcome of people with stroke, with a proportion of Rankin [0–2] score at 3 months of 76.2% and 77.3% of patients in the early- and progressive-sitting groups, respectively (p = 0.52). There was also no difference between groups for secondary outcome measures, and the procedure was well tolerated in both arms.

Conclusion

Due to a slow enrollment, fewer patients than anticipated were available for analysis. As a result, we can only detect beneficial/detrimental effects of +/- 15% of the early sitting procedure on stroke outcome with a realized 37% power. However, enrollment was sufficient to rule out effect sizes greater than 25% with 80% power, indicating that early sitting is unlikely to have an extreme effect in either direction on stroke outcome. Additionally, we were not able to provide a blinded assessment of the primary outcome. Taking these limitations into account, our results may help guide the development of more effective acute stroke rehabilitation strategies, and the design of future acute stroke trials involving out of bed activities and other mobilization regimens.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01573299","term_id":"NCT01573299"}}NCT01573299