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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. 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. 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.

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.

Background: Prior studies have shown an association between jugular venous reflux and age-related neurological conditions, including cognitive decline and potentially incident dementia. However, a relationship between internal jugular vein (IJV) outflow disturbance and cognitive impairment has yet to be elucidated. This study evaluates the relationship between impaired IJV drainage and cognitive function. Methods: We recruited a prospective sample of 106 participants with subjective memory complaints. Subjects underwent neuropsychological assessments and ultrasound examination of IJV, including time-averaged mean velocity (TAMV) and the cross-sectional area of the IJV at the middle (J2) and distal (J3) segments. Impaired IJV drainage was defined by either of the following: (1) TAMV < 4 cm/s at the J2 or J3 segment on either side, or (2) IJV lumen collapse during inspiration at the J2 segment on either side. Results: The impaired cognition group had a significantly higher prevalence of both impaired flow velocity and impaired IJV drainage compared to the normal cognition group (34% vs. 16%, p = 0.032; 68% vs. 30%, p < 0.001). Furthermore, the impaired IJV drainage group demonstrated lower scores across all neuropsychological tests, with statistical significance observed in the Mini-Mental State Examination (median (IQR) 27 vs. 29, p = 0.013), Montreal Cognitive Assessment (median (IQR) 23 vs. 26, p < 0.001) and Chinese Version of the Verbal Learning Test (median (IQR) 23.5 vs. 27, p = 0.024). Notably, incorporating IJV lumen collapse during deep inspiration into the definition of impaired IJV drainage further increased its prevalence in the impaired cognition group. Conclusions: Our results revealed that the impaired cognition group exhibited a higher prevalence of impaired outflow in the bilateral IJV, while the impaired IJV drainage group scored lower on all neuropsychological tests compared to the normal group. These findings support the hypothesis that impaired IJV drainage is correlated with global cognitive decline.

Alcoholism is a complex behavioural disorder. Molecular genetics studies have identified numerous candidate genes associated with alcoholism. It is crucial to verify the disease susceptibility genes by correlating the pinpointed allelic variations to the causal phenotypes. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for ethanol metabolism in humans. Both ADH and ALDH exhibit functional polymorphisms among racial populations; these polymorphisms have been shown to be the important genetic determinants in ethanol metabolism and alcoholism. Here, we briefly review recent advances in genomic studies of human ADH/ALDH families and alcoholism, with an emphasis on the pharmacogenetic consequences of venous blood acetaldehyde in the different ALDH2 genotypes following the intake of various doses of ethanol. This paper illustrates a paradigmatic example of phenotypic verifications in a protective disease gene for substance abuse.

Dopamine plays an important role in the development of alcohol dependence, cognitive dysfunction, and is regulated via dopamine transporter activity. Although dopamine transporter activity is critically involved in alcohol dependence, studies observing this relationship are limited. Thus the current study examined whether dopamine transporter availability is associated with developing of alcohol dependence and cognitive dysfunction. Brain imaging with 99mTc-TRODAT-1 as a ligand was used to measure dopamine transporter availability among 26 male patients with pure alcohol dependence and 22 age- and sex- matched healthy volunteers. The Wisconsin Card Sorting Test (WCST) and Tridimensional Personality Questionnaire (TPQ) were administered to assess neurocognitive functioning and personality traits, respectively. Compared to healthy controls, patients with alcohol dependence showed a significant reduction in dopamine transporter availability (p < 0.001), as well as diminished performance on the WCST (p < 0.001). Dopamine transporter availability was negatively correlated with both total and perseverative WCST errors among healthy controls, but only patients with alcohol dependence showed a positive correlation between dopamine transporter availability and a harm avoidance personality profile. Thus, reductions in dopamine transporter availability may play a pathophysiological role in the development of pure alcohol dependence, given its association with neurocognitive deficits. Moreover, personality may influence the development of pure alcohol dependence; however, additional clinical subgroups should be examined to confirm this possibility.

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.

Inflammation and infection have been noted to increase stroke risk. However, the association between septicaemia and increased risk of stroke remains unclear. This population-based cohort study, using a National Health Insurance database, aimed to investigate whether patients with septicaemia are predisposed to increased stroke risk. The study included all patients hospitalised for septicaemia for the first time between 2000 and 2003 without prior stroke. Patients were followed until the end of 2010 to evaluate incidence of stroke. An age-, gender- and co-morbidities-matched cohort without prior stroke served as the control. Cox's proportional hazards regressions were used to assess differences in stroke risk between groups. Based on hazard ratios (HRs), patients with septicaemia had greater stroke risk, especially in the younger age groups (age <45: HR = 4.16, 95% CI: 2.39-7.24, p<0.001; age 45-64: HR = 1.76, 95% CI: 1.41-2.19, p<0.001; age ≥ 65: HR = 1.05, 95% CI: 0.91-1.22, p>0.05). Haemorrhagic stroke was the dominant type (ischaemic stroke: HR = 1.20, 95% CI: 1.06-1.37, p<0.01; haemorrhagic stroke: HR = 1.82, 95% CI: 1.35-2.46, p<0.001) and patients without co-morbidities were at slightly higher risk (without co-morbidities: HR = 1.49, 95% CI: 1.02-2.17, p<0.05; with co-morbidities: HR = 1.24, 95% CI: 1.10-1.41, p<0.001). The impact of septicaemia on stroke risk was highest within 6 months of the event and gradually declined over time. Our results suggest that septicaemia is associated with an increase in stroke risk, which is greatest in haemorrhagic stroke. Closer attention to patients with history of septicaemia may be warranted for stroke preventive measures, especially for younger patients without co-morbidities.

The aim of this study was to assess the clinical implications of reversed ophthalmic artery flow (ROAF) for stroke risk and outcomes in subjects with unilateral severe cervical carotid stenosis/occlusion. We investigated 128 subjects (101 with acute stroke and 27 without), selected from a large hospital patients base (n  =  14,701), identified with unilateral high-grade cervical carotid stenosis/occlusion by using duplex ultrasonography and brain magnetic resonance imaging. All clinical characteristics were compared for stroke risk between acute stroke and nonstroke groups. Patients with acute stroke were divided into 4 subgroups according to ophthalmic artery flow direction and intracranial stenosis severity, and stroke outcomes were evaluated. The acute stroke group had significantly higher percentages of ROAF (52.5%, p  =  0.003), carotid occlusion (33.7%, p  =  0.046), and severe intracranial stenosis (74.3%, p<0.001). However, multivariate analysis demonstrated that intracranial stenosis was the only significant risk factor (odds ratio  =  10.38; 95% confidence interval  =  3.64-29.65; p<0.001). Analysis of functional outcomes among the 4 subgroups of patients with stroke showed significant trends (p  =  0.018 to 0.001) for better stroke outcomes from ROAF and mild or no intracranial stenosis. ROAF improved 10-20% stroke outcomes, as compared to forward ophthalmic artery flow, among the patients with stroke and the same degree of severities of intracranial stenosis. Patients with acute stroke and severe unilateral cervical carotid stenosis/occlusion significantly have high incidence of intracranial stenosis and ROAF. Intracranial stenosis is a major stroke risk indicator as well as a predictor for worse stroke outcomes, and ROAF may provide partial compensation for improving stroke outcomes.

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.

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.