Core and penumbra estimation using deep learning-based AIF in association with clinical measures in computed tomography perfusion (CTP).

OBJECTIVES: To investigate whether utilizing a convolutional neural network (CNN)-based arterial input function (AIF) improves the volumetric estimation of core and penumbra in association with clinical measures in stroke patients. METHODS: The study included 160 acute ischemic stroke patients (male = 87, female = 73, median age = 73 years) with approval from the institutional review board. The patients had undergone CTP imaging, NIHSS and ASPECTS grading. convolutional neural network (CNN) model was trained to fit a raw AIF curve to a gamma variate function. CNN AIF was utilized to estimate the core and penumbra volumes which were further validated with clinical scores. RESULTS: Penumbra estimated by CNN AIF correlated positively with the NIHSS score (r = 0.69; p < 0.001) and negatively with the ASPECTS (r = - 0.43; p < 0.001). The CNN AIF estimated penumbra and core volume matching the patient symptoms, typically in patients with higher NIHSS (> 20) and lower ASPECT score (< 5). In group analysis, the median CBF < 20%, CBF < 30%, rCBF < 38%, Tmax > 10 s, Tmax > 10 s volumes were statistically significantly higher (p < .05). CONCLUSIONS: With inclusion of the CNN AIF in perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke. CRITICAL RELEVANCE STATEMENT: With CNN AIF perfusion imaging pipeline, penumbra and core estimations are more reliable as they correlate with scores representing neurological deficits in stroke.

The optimal pulse pressures for healthy adults with different ages and sexes correlate with cardiovascular health metrics.

Background: Pulse pressure (PP) may play a role in the development of cardiovascular disease, and the optimal PP for different ages and sexes is unknown. In a prospective cohort, we studied subjects with favorable cardiovascular health (CVH), proposed the mean PP as the optimal PP values, and demonstrated its relationship with healthy lifestyles. Methods and results: Between 1996 and 2016, a total of 162,636 participants (aged 20 years or above; mean age 34.9 years; 26.4% male subjects; meeting criteria for favorable health) were recruited for a medical examination program. PP in male subjects was 45.6 ± 9.4 mmHg and increased after the age of 50 years. PP in female subjects was 41.8 ± 9.5 mmHg and increased after the age of 40 years, exceeding that of male subjects after the age of 50 years. Except for female subjects with a PP of 40-70 mmHg, PP increase correlates with both systolic blood pressure (BP) increase and diastolic BP decrease. Individuals with mean PP values are more likely to meet health metrics, including body mass index (BMI) <25 kg/m2 (chi-squared = 9.35, p<0.01 in male subjects; chi-squared = 208.79, p < 0.001 in female subjects) and BP <120/80 mmHg (chi-squared =1,300, p < 0.001 in male subjects; chi-squared =11,000, p < 0.001 in female subjects). We propose a health score (Hscore) based on the sum of five metrics (BP, BMI, being physically active, non-smoking, and healthy diet), which significantly correlates with the optimal PP. Conclusion: The mean PP (within ±1 standard deviation) could be proposed as the optimal PP in the adult population with favorable CVH. The relationship between health metrics and the optimal PP based on age and sex was further demonstrated to validate the Hscore.

Urgent Demand of Network Access for Acute Ischemic Stroke Management in Taiwan.

Time is the major determinant in successful reperfusion therapy of acute ischemic stroke. The evolving diagnostic tools and treatment of acute stroke has made a great progress in the past 2 decades and is remolding current management practices. It demands a timely neurologic evaluation and a neuroimaging study to determine if stroke patients are appropriate candidates for reperfusion demands. Therefore, it is critical for the setting of stroke center accreditation levels and capabilities so that timely and appropriate treatment is initiated for the eligible stroke patients. Optimal acute ischemic stroke treatment requires all levels of stroke center network operating efficiently. In the future, Taiwan should revise the criteria of stroke center accreditation and set up the efficient acute stroke treatment network as soon as possible. Keywords: stroke, reperfusion, intra-arterial thrombectomy, intravenous recombinant tissue plasminogen activator.

Optimal Scaling Approaches for Perfusion MRI with Distorted Arterial Input Function (AIF) in Patients with Ischemic Stroke.

BACKGROUND: Diagnosis and timely treatment of ischemic stroke depends on the fast and accurate quantification of perfusion parameters. Arterial input function (AIF) describes contrast agent concentration over time as it enters the brain through the brain feeding artery. AIF is the central quantity required to estimate perfusion parameters. Inaccurate and distorted AIF, due to partial volume effects (PVE), would lead to inaccurate quantification of perfusion parameters. METHODS: Fifteen patients suffering from stroke underwent perfusion MRI imaging at the Tri-Service General Hospital, Taipei. Various degrees of the PVE were induced on the AIF and subsequently corrected using rescaling methods. RESULTS: Rescaled AIFs match the exact reference AIF curve either at peak height or at tail. Inaccurate estimation of CBF values estimated from non-rescaled AIFs increase with increasing PVE. Rescaling of the AIF using all three approaches resulted in reduced deviation of CBF values from the reference CBF values. In most cases, CBF map generated by rescaled AIF approaches show increased CBF and Tmax values on the slices in the left and right hemispheres. CONCLUSION: Rescaling AIF by VOF approach seems to be a robust and adaptable approach for correction of the PVE-affected multivoxel AIF. Utilizing an AIF scaling approach leads to more reasonable absolute perfusion parameter values, represented by the increased mean CBF/Tmax values and CBF/Tmax images.

Arterial input function segmentation based on a contour geodesic model for tissue at risk identification in ischemic stroke.

PURPOSE: Perfusion parameters such as cerebral blood flow (CBF) and Tmax have been proven to be useful in the diagnosis and prognosis for ischemic stroke. Arterial input function (AIF) is required as an input to estimate perfusion parameters. This makes the AIF selection paradigm of clinical importance. METHODS: This study proposes a new technique to address the problem of AIF selection, based on a variational segmentation model that combines geometric constraint in a distance function. The modified model uses discrete total variation in the distance term and via minimizing energy locates the arterial regions. Matrix analysis is utilized to identify the AIF with maximum peak height within the segmented region. RESULTS: Group mean differences indicate that overall the AIF selected by the purposed method has better arterial features of higher peak position (16.7 and 26.1 a.u.) and fast attenuation (1.08 s and 0.9 s) as compared to the other state-of-the-art methods. Utilizing the selected AIF, mean CBF, and Tmax values were estimated higher than the traditional methods. Ischemic regions were precisely located through the perfusion maps. CONCLUSIONS: This AIF segmentation framework worked on perfusion images at levels superior to the current clinical state of the art. Consequently, the perfusion parameters derived from AIF selected by the purposed method were more accurate and reliable. The proposed method could potentially be considered as part of the calculation for perfusion imaging in general.

Biomarkers with Plasma Amyloid ß and Tau Protein Assayed by Immunomagnetic Reduction in Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

This review addresses recent developments in the analyses of plasma amyloid beta (Aß) and total tau (t-tau) protein levels as biomarkers for discriminating amnestic mild cognitive impairment (aMCI) from Alzheimer disease (AD), using immunomagnetic reduction (IMR). Recent studies have focused on the differential diagnosis of normal controls (NCs) with aMCI or AD. Results of 15 clinical studies have demonstrated decrease in plasma Aß1-40 and increase in plasma Aß1-42 and t-tau levels in patients with aMCI and AD. For a given biomarker, effect size is determined by comparing the mean ratios of biomarker levels between two diagnostic groups. Effect sizes are less than 1 for Aß1-40 (0.606-1.032) but >1 for Aß1-42 (1.018-2.167) and t-tau (1.030-4.147) in aMCI and AD compared with NCs. The effect size of the plasma tau significantly increases the most as aMCI progresses to AD. Studies into the application of IMR to determine plasma Aß and tau levels as biomarkers for aMCI or AD have recently progressed. Future investigations should validate recently published results, preferably in patients with pathologically confirmed AD. In addition, effort should be directed toward standardizing the design of such studies and data analysis. Keywords: amyloid beta, plasma tau, Alzheimer disease, biomarker, mild cognitive impairment.

Multidisciplinary approach to Fibromyalgia: What are we learning from updated evidence-based medicine?

Fibromyalgia (FM) is a disease characterized by amplified pain responses; here, hyperalgesia occurs in response to noxious stimuli, and allodynia occurs in response to non-noxious stimuli. The diagnosis of FM is often time consuming because it overlaps with psychosomatic symptoms. Indeed, most cases of FM are combined with other comorbidities, such as rheumatological diseases, mental disorders, or gastrointestinal disorders. The main symptoms of FM, which include pain, fatigue, and sleep disturbance, are poorly discriminatory and, thus, greatly increase the difficulty of diagnosis. The 2017 European League Against Rheumatism treatment guidelines of FM recommend that non-pharmacological therapies based on exercise should first be attempted after a diagnosis of FM. Although drug treatments appear to be effective, evidence supporting the use of this treatment modality is relatively weak. Obtaining a broad understanding of FM can help clinicians formulate individualized treatment to improve patient functions and quality of life. Key words: fibromyalgia, diagnostic criteria, non-pharmacological therapy.

Early Rehabilitation after Acute Stroke:The Golden Recovery Period.

Stroke is a leading cause of disability worldwide. Neuroplasticity, a condition wherein the brain's dynamic response to injury is heightened and rehabilitation might be effective, is observed shortly after acute stroke. However, although several trials have demonstrated that initiating treatment within 24 hours after stroke is potentially harmful, some have shown that early rehabilitation of patients is beneficial. Administration of constraint-induced movement therapy within two weeks after stroke appears to be beneficial for the upper extremities. In addition, intensive early post-stroke therapy may be beneficial for patients with severe aphasia. Novel approaches to early treatment of post-stroke dysphagia appear promising; however, the high rate of spontaneous improvement makes it difficult to gauge their benefits. Overall, although increasing evidence indicates that initiating rehabilitative strategies within two weeks after stroke is beneficial for some deficits, the optimal time for initiating post-stroke rehabilitation remains undetermined. Keywords: stroke, early rehabilitation, neuroplasticity, early mobilization.

Long-Term Use of Statins Lowering the Risk of Rehospitalization Caused by Ischemic Stroke Among Middle-Aged Hyperlipidemic Patients: A Population-Based Study.

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis. Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model. Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29-1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users. Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted.

Mathematical Framework of Deconvolution Algorithms for Quantification of Perfusion Parameters.

PURPOSE: MR perfusion weighted imaging (PWI) has been used as sensitive indicator of tissue at risk for infarction. Quantitative perfusion parameters such as cerebral blood flow (CBF), mean transit time (MTT) and cerebral blood volume (CBV) can be obtained from post processing of PWI data using standard singular value decomposition algorithm (SVD). Assumption regarding absence of arterial - tissue delay (ATD) used in SVD algorithm results in underestimation of perfusion parameters. To estimate accurate values for perfusion parameters it is important to understand the mathematical framework behind SVD and improved SVD algorithms (bSVD and rSVD). METHOD: This study explains the mathematical framework of SVD and improved SVD algorithms and uses computational techniques that use bSVD algorithm to obtain perfusion parameters maps of CBF, CBV and MTT for acute stroke patient. RESULT: Computational techniques based on mathematical deconvolution algorithms are used to post process CBV, CBF and MTT maps where decrease in CBF and CBV were seen in left hemisphere. CONCLUSION: The bSVD algorithm is found to be sensitive to ATD and provides more accurate estimates of perfusion parameters than the SVD algorithm, however CBF estimates from bSVD and rSVD still remain influenced by other artifacts Keywords: PWI = perfusion weighted imaging, CBF= cerebral blood flow, MTT = mean transit time, CBV= cerebral blood volume, SVD = singular value decomposition algorithm.

A 48-Week, Multicenter, Open-Label, Observational Study Evaluating Oral Rivastigmine in Patients with Mild-to-Moderate Alzheimer's Disease in Taiwan.

INTRODUCTION: Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer's type. This study assessed the short- and long-term effectiveness and safety of rivastigmine in patients with mild-to-moderate Alzheimer's disease (AD) in a real-world clinical setting in Taiwan. METHODS: This was a 48-week, single-arm, open-label, prospective, observational, post-marketing surveillance, multicenter study. The primary outcomes were change from baseline to week 48 in the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) scores. One-year persistence to treatment, effect on activities of daily living, and incidence of adverse events (AEs) were also assessed. RESULTS: Overall, 151 patients were enrolled in the study, of which 91 (60.26%) completed this study. At the end of the study, the mean rivastigmine dose received by the patients was 6.59 mg/day. At week 48, the changes in mean [standard deviation (SD)] MMSE and CDR scores in the intent-to-treat (ITT) population from baseline were - 1.00 (3.8; p = 0.0344) and 0.07 (0.29; p = 0.0403), respectively. The most frequently reported AEs by preferred term were dizziness (12.58%) and nausea (9.27%). No new or unexpected AEs were observed, and 30 (20.13%) patients in the ITT population were on rivastigmine therapy for 1 year without treatment discontinuation. CONCLUSION: Despite the low 1-year persistence rate, rivastigmine showed a stabilizing effect on declining cognition in patients with mild-to-moderate AD in a real-world scenario. Rivastigmine is well tolerated at 6.0-9.0 mg/day with no unexpected safety concerns. FUNDING: Novartis Co. Ltd., Taipei, Taiwan.

Development of an intelligent decision support system for ischemic stroke risk assessment in a population-based electronic health record database.

BACKGROUND: Intelligent decision support systems (IDSS) have been applied to tasks of disease management. Deep neural networks (DNNs) are artificial intelligent techniques to achieve high modeling power. The application of DNNs to large-scale data for estimating stroke risk needs to be assessed and validated. This study aims to apply a DNN for deriving a stroke predictive model using a big electronic health record database. METHODS AND RESULTS: The Taiwan National Health Insurance Research Database was used to conduct a retrospective population-based study. The database was divided into one development dataset for model training (~70% of total patients for training and ~10% for parameter tuning) and two testing datasets (each ~10%). A total of 11,192,916 claim records from 840,487 patients were used. The primary outcome was defined as any ischemic stroke in inpatient records within 3 years after study enrollment. The DNN was evaluated using the area under the receiver operating characteristic curve (AUC or c-statistic). The development dataset included 672,214 patients (a total of 8,952,000 records) of whom 2,060 patients had stroke events. The mean age of the population was 35.5±20.2 years, with 48.5% men. The model achieved AUC values of 0.920 (95% confidence interval [CI], 0.908-0.932) in testing dataset 1 and 0.925 (95% CI, 0.914-0.937) in testing dataset 2. Under a high sensitivity operating point, the sensitivity and specificity were 92.5% and 79.8% for testing dataset 1; 91.8% and 79.9% for testing dataset 2. Under a high specificity operating point, the sensitivity and specificity were 80.3% and 87.5% for testing dataset 1; 83.7% and 87.5% for testing dataset 2. The DNN model maintained high predictability 5 years after being developed. The model achieved similar performance to other clinical risk assessment scores. CONCLUSIONS: Using a DNN algorithm on this large electronic health record database is capable of obtaining a high performing model for assessment of ischemic stroke risk. Further research is needed to determine whether such a DNN-based IDSS could lead to an improvement in clinical practice.

Prevalence and clinical characteristics of stroke patients with p.R544C NOTCH3 mutation in Taiwan.

Objective: Features of cerebral autosomal dominant arteriopathy with subcortical infarct and leukoencephalopathy ( CADASIL) caused by NOTCH3 mutations vary between ethnicities and regions. In Taiwan, more than 70% of CADASIL patients carry the mutation hot spot of p.R544C. We investigated the prevalence of NOTCH3 p.R544C mutation in stroke patients in Taiwan. Methods: This prospective, multicenter study recruited acute stroke patients within 10 days of symptom onset. The p.R544C mutation was identified by polymerase chain reaction with confronting two-pair primers and sequencing. Clinical parameters, vascular risk factors, stroke subtypes, and stroke outcomes were analyzed. Results: Of the 1970 stroke patients (mean age 61.1 ± 13.6 years, male 69.5%) included, 1705 (86.5%) had ischemic stroke and 265 (13.5%) had intracerebral hemorrhage. The prevalence of p.R544C in the study population was 2.8% (95% confidence interval [CI] = 2.1-3.5%). The prevalence was highest in patients with small vessel occlusion type of ischemic stroke (5.6%), followed by intracerebral hemorrhage (5.3%), and infarct of undetermined etiology (2.7%), and was low in patients with cardioembolism (0.8%) and large artery atherosclerosis (0.7%). All p.R544C patients with intracerebral hemorrhage were nonlobar hemorrhage. Sibling history of stroke (odds ratio [OR] = 4.50, 95% CI = 1.67-12.14 in ischemic stroke; OR = 6.03, 95% CI = 1.03-35.47 in intracerebral hemorrhage, respectively) and small vessel occlusion (OR, 4.03, 95% CI, 1.26-12.92) were significantly associated with p.R544C. Interpretation: p.R544C NOTCH3 mutation is underdiagnosed in stroke patients in Taiwan, especially in those with small vessel occlusion and sibling history of stroke.

Valproate is protective against 6-OHDA-induced dopaminergic neurodegeneration in rodent midbrain: A potential role of BDNF up-regulation.

BACKGROUND/PURPOSE: The main purpose of this study was to extend previously reported showing potent neuroprotective effect of valproic acid (VPA) in primary midbrain neuro-glial cultures to investigate whether VPA could protect dopamine (DA) neurons in vivo against 6-hydroxydopamine (6-OHDA)-induced neurodegeneration and to determine the underlying mechanism. METHODS: Male adult rats received a daily intraperitoneal injection of VPA or saline for two weeks before and after injection of 5, 10, or 15 µg of 6-OHDA into the brain. All rats were evaluated for motor function by rotarod performance. Brain samples were prepared for immunohistochemical staining and for determination of levels of dopamine, dopamine metabolites, and neurotrophic factors. RESULTS: 6-OHDA injection showed significant and dose-dependent damage of dopaminergic neurons and decrease of striatal dopamine content. Rats in the VPA-treated group were markedly protected from the loss of dopaminergic neurons and showed improvements in motor performance, compared to the control group at the moderate 6-OHDA dose (10 µg). VPA-treated rats also showed significantly increased brain-derived neurotrophic factor (BDNF) levels in the striatum and substantia nigra compared to the levels in control animals. CONCLUSION: Our studies demonstrate that VPA exerts neuroprotective effects in a rat model of 6-OHDA-induced Parkinson's disease (PD), likely in part by up-regulation BDNF.

Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

Changes in sensorimotor-related thalamic diffusion properties and cerebrospinal fluid hydrodynamics predict gait responses to tap test in idiopathic normal-pressure hydrocephalus.

OBJECTIVES: To compare diffusion tensor (DT)-derived indices from the thalamic nuclei and cerebrospinal fluid (CSF) hydrodynamic parameters for the prediction of gait responsiveness to the CSF tap test in early iNPH patients. METHODS: In this study, 22 patients with iNPH and 16 normal controls were enrolled with the approval of an institutional review board. DT imaging and phase-contrast magnetic resonance imaging were performed in patients and controls to determine DT-related indices of the sensorimotor-related thalamic nuclei and CSF hydrodynamics. Gait performance was assessed in patients using gait scale before and after the tap test. The Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis were applied to compare group differences between patients and controls and assess the predictive performance of gait responsiveness to the tap test in the patients. RESULTS: Fractional anisotropy (FA) and axial diffusivity showed significant increases in the ventrolateral (VL) and ventroposterolateral (VPL) nuclei of the iNPH group compared with those of the control group (p < 0.05). The predictions of gait responsiveness of ventral thalamic FA alone (area under the ROC curve [AUC] < 0.8) significantly outperformed those of CSF hydrodynamics alone (AUC < 0.6). The AUC curve was elevated to 0.812 when the CSF peak systolic velocity and FA value were combined for the VPL nucleus, yielding the highest sensitivity (0.769) and specificity (0.778) to predict gait responses. CONCLUSIONS: Combined measurements of sensorimotor-related thalamic FA and CSF hydrodynamics can provide potential biomarkers for gait response to the CSF tap test in patients with iNPH. KEY POINTS: • Ventrolateral and ventroposterolateral thalamic FA may predict gait responsiveness to tap test. • Thalamic neuroplasticity can be assessed through DTI in idiopathic normal-pressure hydrocephalus. • Changes in the CST associated with gait control could trigger thalamic neuroplasticity. • Activities of sensorimotor-related circuits could alter in patients with gait disturbance. • Management of patients with iNPH could be more appropriate.

Lumbar Dorsal Root Ganglion Block as a Prognostic Tool Before Pulsed Radiofrequency: A Randomized, Prospective, and Comparative Study on Cost-Effectiveness.

OBJECTIVES: In the study, we discuss the predictive value and cost-effectiveness of dorsal root ganglion (DRG) blocks before using dorsal root ganglion pulsed radiofrequency (DRG-PRF) in the treatment of low back pain. METHODS: The study comprised 60 patients with low back pain who were randomly assigned into 2 groups. Patients in group 1 were screened using DRG block before DRG-PRF treatment for responders. Patients in group 2 underwent DRG-PRF treatment without DRG block. Successful outcome was defined as patient satisfaction, improvement in numerical rating scale, and medication use reduction. RESULTS: In group 1 (n = 30), 24 patients demonstrated good response to DRG block, and 20 patients had successful outcome at 6 months after DRG-PRF therapy. In group 2 (n = 30), 25 of the patients had successful outcome at 6 months after DRG-PRF therapy. The mean medical costs were NT$ 19,245 and NT$ 16,375 for each successful case in groups 1 and 2, respectively. CONCLUSIONS: In this comparative cost-effectiveness study, the application of diagnostic DRG blocks before DRG-PRF did not have a significant impact on patient satisfaction, pain index score, or pain medication reduction. Furthermore, the application of diagnostic DRG blocks resulted in overall greater medical costs. These findings suggest that DRG-PRF without screening by DRG block is more cost-effective and less invasive.

Nationwide "Hospital Emergent Capability Accreditation by Level-Stroke" Improves Stroke Treatment in Taiwan.

BACKGROUND AND PURPOSE: Recombinant tissue plasminogen activator (rtPA) is one of the proven therapies that improve the outcome of patients with acute ischemic stroke (AIS). In 2009, the Ministry of Health and Welfare, Executive Yuan, Republic of China, launched the project "Hospital Emergent Capability Accreditation by Level-Stroke (HECAL-Stroke)" to improve AIS treatment in Taiwan. The current study was performed to determine whether the project launched by the government was effective in promoting rtPA therapy among AIS patients. METHODS: All participating hospitals were verified and designated as "heavy duty (HD)," "moderate duty (MoD)," or "medium duty (MeD)" according to the stroke center criteria. Four annual indices (rates of treatment, protocol adherence, in-time treatment, and complications) were recorded from 2009 to 2014 as outcome measures. The data were analyzed using the χ2 test for significance. RESULTS: The number of certified hospitals progressively increased from 74 to 112 during the 6-year period and finally consisted of 33 HD, 9 MoD and 70 MeD hospitals in 2014. The annual intravenous rtPA treatment rate increased significantly from 3.0% in 2009 to 4.5% in 2014. The protocol adherence rates were 95.7% in the HD group, 92.4% in the MoD group and 72.8% in the MeD group. The annual in-time treatment rate significantly improved from 26.0% in 2009 to 60.1% in 2014. The overall symptomatic intracranial hemorrhagic rate after rtPA treatment was 8.6%. CONCLUSIONS: Initiation of the HECAL-Stroke project by the government significantly improved rtPA treatment in Taiwan.

Usefulness of glycated hemoglobin A1c-based adjusted glycemic variables in diabetic patients presenting with acute ischemic stroke.

Acute hyperglycemia is a common condition among patients with diabetes who are admitted to the emergency department (ED) for acute ischemic stroke (AIS). Previous findings regarding the association between hyperglycemia at admission and adverse outcomes among patients with diabetes and AIS have been inconsistent. When investigating this association, it is necessary to consider premorbid blood glucose control. The objective of the current study was to assess whether HbA1c-based adjusted glycemic variables were associated with unfavorable outcomes among patients admitted to the hospital for AIS. We retrospectively analyzed data from 309 patients who were hospitalized for AIS at a single medical center in Taiwan between January 1, 2013, and October 31, 2015. We found that 1) HbA1c-based adjusted glycemic variables, including the glycemic gap and stress hyperglycemia ratio, were associated with both AIS severity and neurological status at discharge; additionally, 2) HbA1c-based adjusted glycemic variables showed superior discriminative power compared with acute hyperglycemia regarding the development of severe AIS. We conclude that both the glycemic gap and stress hyperglycemia ratio might be useful in assessing the disease severity and prognosis of patients presenting with AIS. Further prospective long-term follow-up studies should be performed to validate these findings.

Associations of estradiol levels and genetic polymorphisms of inflammatory genes with the risk of ischemic stroke.

BACKGROUND: Estrogen plays an important role as an anti-inflammatory and neuroprotective agent in ischemic stroke. In this study, we analyzed the effect of a polygenic risk score (PRS) constructed using inflammatory genes and estradiol levels on the risk of ischemic stroke. METHODS: This case-control study was conducted with 624 ischemic stroke patients and 624 age- and gender-matched controls. The PRS estimated the polygenic contribution of inflammatory genes from ischemic stroke susceptibility loci. Estradiol levels were measured using a radioimmunoassay. High and low estradiol levels were defined according to the log-transformed median estradiol levels in female and male controls. RESULTS: Subjects in the fourth quartile of the PRS had a significant 1.57-fold risk of ischemic stroke (95% confidence interval [CI], 1.12 ~ 2.19), after adjusting for covariates compared to individuals in the lowest quartile. Compared to individuals with high estradiol levels and a low PRS as the reference group, those exposed to low estradiol levels and a high PRS had an increased risk of ischemic stroke (odds ratio, 3.35; 95% CI, 1.79 ~ 6.28). Similar results were also observed in males when the analysis was stratified by gender. CONCLUSIONS: Our data suggest that the PRS can be useful in evaluating a high risk of ischemic stroke among patients, especially those exposed to low estradiol levels.