The analysis of brain functional connectivity of post-stroke cognitive impairment patients: an fNIRS study.

Background: Post-stroke cognitive impairment (PSCI) is a considerable risk factor for developing dementia and reoccurrence of stroke. Understanding the neural mechanisms of cognitive impairment after stroke can facilitate early identification and intervention. Objectives: Using functional near-infrared spectroscopy (fNRIS), the present study aimed to examine whether resting-state functional connectivity (FC) of brain networks differs in patients with PSCI, patients with Non-PSCI (NPSCI), and healthy controls (HCs), and whether these features could be used for clinical diagnosis of PSCI. Methods: The present study recruited 16 HCs and 32 post-stroke patients. Based on the diagnostic criteria of PSCI, post-stroke patients were divided to the PSCI or NPSCI group. All participants underwent a 6-min resting-state fNRIS test to measure the hemodynamic responses from regions of interests (ROIs) that were primarily distributed in the prefrontal, somatosensory, and motor cortices. Results: The results showed that, when compared to the HC group, the PSCI group exhibited significantly decreased interhemispheric FC and intra-right hemispheric FC. ROI analyses showed significantly decreased FC among the regions of somatosensory cortex, dorsolateral prefrontal cortex, and medial prefrontal cortex for the PSCI group than for the HC group. However, no significant difference was found in the FC between the PSCI and the NPSCI groups. Conclusion: Our findings provide evidence for compromised interhemispheric and intra-right hemispheric functional connectivity in patients with PSCI, suggesting that fNIRS is a promising approach to investigate the effects of stroke on functional connectivity of brain networks.

The regulations on cortical activation and functional connectivity of the dorsolateral prefrontal cortex-primary somatosensory cortex elicited by acupuncture with reinforcing-reducing manipulation.

Introduction: Traditional acupuncture with reinforcing-reducing manipulation is essential for clinical effectiveness, whereas the underlying central mechanism of it remains unknown. This study with multiple-channels functional near-infrared spectroscopy (fNIRS) aims to explore cerebral-response modes during acupuncture with reinforcing-reducing manipulations. Materials and methods: Functional near-infrared spectroscopy data were recorded from 35 healthy participants during the lifting-thrusting reinforcing manipulation, the lifting-thrusting reducing manipulation, and the even reinforcing-reducing manipulation with lifting-thrusting. The general linear model based (GLM) cortical activation analysis and the functional connectivity (FC) based on region of interest (ROI) analysis were combined to be conducted. Results: In comparison with the baseline, the results showed that three acupuncture with reinforcing-reducing manipulations similarly induced the hemodynamic responses in the bilateral dorsolateral prefrontal cortex (DLPFC) and increased FC between the DLPFC and primary somatosensory cortex (S1). Specifically, the even reinforcing-reducing manipulation deactivated the bilateral DLPFC, the frontopolar area (FP), the right primary motor cortex (M1), the bilateral S1, and the bilateral secondary somatosensory cortex (S2); The reducing manipulation deactivated the bilateral DLPFC; The reinforcing manipulation activated the bilateral DLPFC, the left S1, and the right S2. The between-group comparisons indicated that the reinforcing-reducing manipulation induced opposite hemodynamic responses in the bilateral DLPFC and the left S1 and exhibited different FC patterns in the left DLPFC-S1, within the right DLPFC, and between the left S1 and the left orbitofrontal cortex (OFC). Conclusion: These findings verified the feasibility of fNIRS for investigating cerebral functional activities of acupuncture manipulations, suggesting that the regulations on the DLPFC-S1 cortex may be the potential central mechanism for the realization of acupuncture with reinforcing-reducing manipulation's effect. Clinical trial registration: ClinicalTrials.gov, identifier, ChiCTR2100051893.

The increased inter-brain neural synchronization in prefrontal cortex between simulated patient and acupuncturist during acupuncture stimulation: Evidence from functional near-infrared spectroscopy hyperscanning.

The patient-acupuncturist interaction was a critical influencing factor for acupuncture effects but its mechanism remains unclear. This study aimed to examine the inter-brain mechanism of patient-acupuncturist dyad during acupuncture stimulation in a naturalistic clinical setting. Seventy healthy subjects (simulated "patients") were randomly assigned to two groups and received verum acupuncture group or sham acupuncture by one acupuncturist. Functional near-infrared spectroscopy hyperscanning was used to simultaneously record the neural responses of "patient"-acupuncturist dyad during acupuncture stimulation in each group. The results showed that inter-brain neural synchronization (INS) in the prefrontal cortex (PFC) of "patient"-acupuncturist dyad was significantly increased during verum but not sham acupuncture stimuli, and positively correlated with the needling sensations of "patients." Granger causality analysis demonstrated that there were no significant differences in INS direction between the "patient" and the acupuncturist. This study identified the increase of INS between "patient" and acupuncturist, and suggested that PFC was important to the interaction of "patient"-acupuncturist dyad.

Methodological issues of the central mechanism of two classic acupuncture manipulations based on fNIRS: suggestions for a pilot study.

Background: Acupuncture reinforcing-reducing manipulation (ARRM) is a necessary procedure of traditional Chinese acupuncture and an essential factor affecting the therapeutic effect of acupuncture. Shaoshanhuo reinforcing method (SSH) and Toutianliang reducing method (TTL) are the most representative ARRMs. They integrate six single ARRMs and pose distinguished therapeutic effects of acupuncture. However, due to the complexity, diversity, and variation, investigating the mechanism of these two classic manipulations is insufficient. The neuroimaging technique is an important method to explore the central mechanism of SSH and TTL. This study attempted to design a randomized crossover trial based on functional near-infrared spectroscopy (fNIRS) to explore the mechanism of SSH and TTL, meanwhile, provide valuable methodological references for future studies. Methods: A total of 30 healthy subjects were finally included and analyzed in this study. fNIRS examination was performed to record the neural responses during the two most representative ARRMs. The cortical activation and the inter-network functional connectivity (FC) were explored. Results: The results found that SSH and TTL could elicit significant cerebral responses, respectively, but there was no difference between them. Conclusion: Neuroimaging techniques with a higher spatiotemporal resolution, combinations of therapeutic effects, and strict quality control are important to neuroimaging studies on SSH and TTL.

Meta-analysis of the association between CHCHD10 Pro34Ser variant and the risk of amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS), one of the motor neuron diseases, appears to be caused by genetic and environmental risk factors. However, the influence of Pro34Ser variant of CHCHD10 gene in increasing risk of ALS remains indeterminate. This study conducted a meta-analysis to establish the association between Pro34Ser variant of CHCHD10 gene and risk of ALS. METHODS: PubMed, Web of Science, and Embase databases were systematically searched for genome-wide association studies or case-control studies published up to March 28, 2020, on the association between Pro34Ser variant and risk of ALS. Data from eligible studies were extracted and analyzed. RESULTS: Twelve case-control studies involving 7442 patients with sporadic ALS and 75,371 controls were analyzed. The Pro34Ser variant was not associated with increased risk of ALS disease based on fixed-effects meta-analysis (Pro34Ser-positive vs Pro34Ser-negative: OR 1.23, 95% CI 0.90 to 1.69, P = 0.201). CONCLUSION: Existing evidence suggests that Pro34Ser variant in CHCHD10 is not associated with risk of ALS, particularly in Caucasian participants. However, our results ought to be validated using large, well-designed studies, especially in Asian and African populations.

Statin Use and the Risk of Prostate Cancer in Ischemic Heart Disease Patients in Taiwan.

Patients with ischemic heart disease (IHD) are more likely to be diagnosed with prostate cancer. Statins, which are widely used in such patients, are shown to modify the risk of prostate cancer. To clarify the association between statin use and the risk of prostate cancer among patients with higher risk of developing prostate cancer in Taiwan, a cohort of 26,628 men with IHD and aged between 55 and 100 were acquired from the National Health Insurance Research Database and followed over a period of 8 years. The risk of prostate cancer was calculated by time-dependent Cox regression model. Statin use was associated with significantly lower risk of both total and advanced prostate cancer (adjusted hazard ratio (HR): 0.719, 95% confidence interval (CI): 0.570-0.908; adjusted HR: 0.718, 95% CI: 0.530-0.972 respectively). In Taiwan IHD population, the reduction in risk of prostate cancer was observed in statin users as compared with nonusers.

Risk of stroke associated with use of nonsteroidal anti-inflammatory drugs during acute respiratory infection episode.

BACKGROUND: Previous studies suggested that acute respiratory infection (ARI) could trigger stroke and that use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with increased risk of stroke. In many countries, NSAIDs have been widely used among patients with ARI or common cold for pain and fever relief. However, studies evaluating whether NSAIDs use during ARI episodes may further increase the risk of stroke were very limited. METHODS AND RESULTS: During 2007 to 2011, 29 518 patients with an incident hospitalization of stroke were identified. The date of admission was defined as the index date. Using case-crossover design, we compared the following exposure status between the case period (1- to 7-d period before the index date) and matched control period (366- to 372-d period before the index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional regression models were used to estimate odds ratios adjusting potential confounders. The results suggested that NSAIDs use during ARI episodes was associated with a 2.3-fold increased risk of stroke (ischemic: adjusted odds ratio, aOR 2.27, 95% confidence interval, 95% CI, 2.00-2.58; hemorrhagic: aOR 2.28, 95% CI, 1.71-3.02). We also determined that parenteral NSAIDs were associated with much higher risk of stroke in patients with ARI. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs use, was associated with a further increased risk of stroke.

Identifying Unmet Treatment Needs for Patients With Osteoporotic Fracture: Feasibility Study for an Electronic Clinical Surveillance System.

BACKGROUND: Traditional clinical surveillance relied on the results from clinical trials and observational studies of administrative databases. However, these studies not only required many valuable resources but also faced a very long time lag. OBJECTIVE: This study aimed to illustrate a practical application of the National Taiwan University Hospital Clinical Surveillance System (NCSS) in the identification of patients with an osteoporotic fracture and to provide a high reusability infrastructure for longitudinal clinical data. METHODS: The NCSS integrates electronic medical records in the National Taiwan University Hospital (NTUH) with a data warehouse and is equipped with a user-friendly interface. The NCSS was developed using professional insight from multidisciplinary experts, including clinical practitioners, epidemiologists, and biomedical engineers. The practical example identifying the unmet treatment needs for patients encountering major osteoporotic fractures described herein was mainly achieved by adopting the computerized workflow in the NCSS. RESULTS: We developed the infrastructure of the NCSS, including an integrated data warehouse and an automatic surveillance workflow. By applying the NCSS, we efficiently identified 2193 patients who were newly diagnosed with a hip or vertebral fracture between 2010 and 2014 at NTUH. By adopting the filter function, we identified 1808 (1808/2193, 82.44%) patients who continued their follow-up at NTUH, and 464 (464/2193, 21.16%) patients who were prescribed anti-osteoporosis medications, within 3 and 12 months post the index date of their fracture, respectively. CONCLUSIONS: The NCSS systems can integrate the workflow of cohort identification to accelerate the survey process of clinically relevant problems and provide decision support in the daily practice of clinical physicians, thereby making the benefit of evidence-based medicine a reality.

Effectiveness of a combination of ezetimibe and statins in patients with acute coronary syndrome and multiple comorbidities: A 6-year population-based cohort study.

BACKGROUND: The clinical benefits of a combination of statins and ezetimibe in patients with acute coronary syndrome (ACS) were observed in a clinical trial. However, little is known regarding the effectiveness of using statins with or without ezetimibe in patients with ACS and multiple comorbidities in real-world clinical practice. METHODS: This is a nationwide population-based cohort study using Taiwan National Health Insurance Research Database. A total of 212,110 patients with ACS who had been discharged after their first ACS events between 2006 and 2010 were enrolled. A propensity score matching approach was used to create matched cohorts for adjusting potential confounders. Cox proportional hazards regressions were performed to estimate the risk of re-hospitalization for ACS and revascularization. RESULTS: Patients in the statins-plus-ezetimibe group had a significantly lower risk of re-hospitalization for ACS (adjusted hazard ratio [HR]=0.64, 95% confidence interval [CI]: 0.60-0.69) and revascularization (HR=0.69, 95% CI: 0.63-0.76) than those in the statins-alone group. In the statins-plus-ezetimibe group, female patients had a lower risk of re-hospitalization for ACS than male patients did, and patients without diabetes mellitus had a lower risk of re-hospitalization for ACS than did patients with diabetes mellitus. CONCLUSIONS: Patients with ACS and multiple comorbidities receiving a combination therapy of statins and ezetimibe had a lower risk of re-hospitalization for ACS and revascularization than those receiving statins alone. Significant interaction effects were observed between combination with ezetimibe, sex, and diabetes mellitus.

Acute Respiratory Infection and Use of Nonsteroidal Anti-Inflammatory Drugs on Risk of Acute Myocardial Infarction: A Nationwide Case-Crossover Study.

Background: Previous studies have suggested that acute respiratory infection (ARI) and nonsteroidal anti-inflammatory drugs (NSAIDs) use could trigger acute myocardial infarction (AMI). In some countries, physicians prescribe NSAIDs for patients with ARI for symptom relief. However, there is no research evaluating whether NSAIDs use during ARI episodes may increase the risk of AMI. Methods: We identified 9793 patients with an incident hospitalization of AMI (index date) between 2007 and 2011. Using case-crossover design, we compared the following exposure status between the case (1-7-day before index date) and matched control period (366-372-day before index date): NSAIDs use during ARI episodes, ARI episodes without NSAIDs use, NSAIDs use only, or no exposure. Multivariable conditional logistic regression models were used to estimate odds ratios adjusted for potential confounders. Results: Nonsteroidal anti-inflammatory drugs use during ARI was associated with a 3.4-fold increased risk of AMI (adjusted odds ratio [aOR] = 3.41; 95% confidence interval [CI] = 2.80-4.16), ARI without NSAIDs use was associated with a 2.7-fold increased risk (aOR = 2.65; 95% CI = 2.29-3.06), and NSAIDs use only was associated with a 1.5-fold increased risk (aOR = 1.47; 95% CI = 1.33-1.62). Moreover, parenteral NSAIDs were associated with much higher risk in ARI patients (aOR = 7.22; 95% CI = 4.07-12.81). Conclusions: Nonsteroidal anti-inflammatory drugs use during ARI episodes, especially parenteral NSAIDs, was associated with a further increased risk of AMI.

Concomitant use of calcium channel blockers with dual antiplatelet therapy and re-hospitalization for acute coronary syndrome.

BACKGROUND: Existing studies suggested that concomitant use of calcium channel blockers (CCBs) may interfere with the antiplatelet effect of clopidogrel. The objective of this study was to examine the effect of concomitant use of CCBs and clopidogrel on risks of acute coronary syndrome (ACS) re-hospitalization in patients receiving percutaneous coronary intervention. METHODS: Using the Taiwan National Health Insurance Research Database, we identified 51 925 patients who were admitted for newly diagnosed ACS, received percutaneous coronary intervention, and used clopidogrel within 1 year after discharge. We further stratified them into three groups based on their uses of guideline-recommended secondary prevention medications for ACS (fully, partially, and non-compliant groups) to assess the potential modification effect of guideline compliance. For each group, we conducted a 1:1 propensity score matching to minimize selection bias. Cox proportional hazard models were used to investigate the effect of concomitant use of CCBs (overall, subclasses, and individual CCBs) and clopidogrel on risks of ACS re-hospitalization. RESULTS: Concomitant use of CCBs in patients discharged with clopidogrel was significantly associated with a lower risk of ACS re-hospitalization in the fully compliant group (HRfully compliant = 0.82 [95% confidence interval 0.75-0.89], p < 0.001) but was associated with increased risk of ACS re-hospitalization in the non-compliant group (HRnon-compliant = 1.22 [1.03-1.45], p = 0.0252). CONCLUSIONS: Different guideline compliance of secondary prevention medications could modify the potential drug-drug interaction between clopidogrel and CCBs. Concomitant use of CCBs and clopidogrel was significantly associated with increased risk of ACS re-hospitalization in ACS patients not compliant to guideline-recommended secondary prevention drugs. Copyright © 2017 John Wiley & Sons, Ltd.

Factors driving the use of warfarin and non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

BACKGROUND/PURPOSE: In the past, warfarin was the drug of choice for stroke prevention in patients with atrial fibrillation (AF). Recently, non-vitamin K antagonist oral anticoagulants (NOACs) have been approved as an alternative to warfarin in nonvalvular AF. However, there is a limited amount of real-world data on how NOACs are currently being used in Taiwan. This study was conducted to investigate the factors driving the initiation of anticoagulants and the selection of different anticoagulants in patients with AF. METHODS: We used National Taiwan University Hospital's electronic database to identify all nonvalvular AF patients from January 1, 2007 to December 31, 2013. Multivariate logistic regression models were used to examine the factors driving the initiation of anticoagulants and the selection of different anticoagulants. RESULTS: Among AF patients, 66.4% of anticoagulants users used NOACs instead of warfarin after the era of NOACs. Patients with female sex, hypertension, ischemic heart disease, cancer, hepatic disease, renal disease, bleeding history, and aspirin use were less likely to be anticoagulant users but are more likely to be anticoagulant users with a history of stroke (odds ratio = 2.64; 95% confidence interval, 2.02-3.45). Older age, ischemic heart disease, and aspirin use were the factors associated with NOACs usage, whereas hepatic disease showed the opposite results (odds ratio = 0.09; 95% confidence interval, 0.02-0.42). CONCLUSION: Stroke history was associated with anticoagulant use, whereas comorbidities associated with increased risk of bleeding showed the opposite result. Patients with hepatic disease were less likely to use NOACs.

SNP rs1805874 of the Calbindin1 Gene Is Associated with Parkinson's Disease in Han Chinese.

AIMS: The single-nucleotide polymorphism, rs1805874, in the Calbindin1 gene has been associated with Parkinson's disease among the Japanese people, but not among Europeans or Americans. To help clarify these contrasting results, we conducted a case-control study to explore whether such an association exists among the Han Chinese. METHODS: We used the ligase detection reaction to genotype the rs1805874 SNP in 514 Han Chinese with Parkinson's disease as well as in 475 healthy Han Chinese controls. RESULTS: We identified a significant association between the A allele of rs1805874 and the risk of Parkinson's disease (OR 1.257, 95% CI 1.036-1.524, p = 0.020). Subgroup analysis revealed a significant association of the A allele with male gender (OR 1.306, 95% CI 1.009-1.691, p = 0.042) and late onset of disease (OR 1.247, 95% CI 1.010-1.540, p = 0.040). CONCLUSION: Our findings suggest that the A allele of rs1805874 is associated with risk of Parkinson's disease among the Han Chinese. Our results, combined with previous studies, suggest that rs1805874 is associated with Parkinson's disease in East Asians, but not Caucasians.

Statin Use and the Risk for Incident Diabetes Mellitus in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Population-Based Retrospective Cohort Study in Taiwan.

OBJECTIVES: The purpose of this study was to examine the association between statin use by individuals and the risk for incident diabetes mellitus in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI). METHODS: We conducted a retrospective cohort study of patients who were hospitalized for ACS between January 1, 2006, and December 31, 2010, and who had undergone PCI (n=30,665); the data were retrieved from the Taiwan National Health Insurance Research Database. A propensity score technique was used to establish a 1:1 matched cohort for statin users and non-statin users (n=9043 for each group). The risk for incident diabetes mellitus in statin users compared to non-statin users for patients with ACS after PCI was estimated by the multivariable Cox proportional hazards regression model. RESULTS: Statin use was associated with a significant increase of 27% in the risk for new-onset diabetes mellitus (adjusted hazard ratio [HR] 1.27, 95% CI 1.14 to 1.41) compared to non-statin use in the matched cohort. The matched cohort analysis indicated that almost all individual statins were associated with a statistically significant increase in the risk for new-onset diabetes mellitus compared to those without statin use. CONCLUSIONS: Our study indicated an association between increased risk for new-onset diabetes mellitus and statin use. Because the benefits of statins in prevention of morbidity and mortality in patients with ACS are well-established, clinical decision making should not be changed for patients with existing cardiovascular disease in whom statin therapy is recommended.

Lack of evidence for an association between the V393A variant of COQ2 and amyotrophic lateral sclerosis in a Han Chinese population.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder involving the degeneration of motor neurons. ALS shares pathogenic characteristics and genetic risk factors with multiple system atrophy (MSA). Here we examine whether a variant of the COQ2 gene associated with MSA in Japanese is also associated with ALS in Han Chinese. The ligase detection reaction was used to measure the frequency of the V393A variant of COQ2 in 282 patients with ALS and 491 healthy controls. The ALS and control groups showed no significant differences in genotype frequencies (OR 1.298, 95 %CI 0.396-4.253, p = 0.666) or allele frequencies (OR 1.314, 95 %CI 0.403-4.286, p = 0.650) at the V393A locus of COQ2. We also conducted a meta-analysis and combined our data with the previous Japanese research, but still failed to detect an association between V393A and ALS. In conclusion, This case-control study shows no evidence for an association between ALS and the V393A variant of COQ2 in Han Chinese and together with the Japanese research suggests that this polymorphism may not be linked to the risk of ALS in East Asians in general.

SNP rs7684318 of the alpha-synuclein gene is associated with Parkinson's disease in the Han Chinese population.

Mutations in the alpha-synuclein (SNCA) gene have been shown to be responsible for a rare familial form of Parkinson's disease (PD). Furthermore, polymorphic variants in multiple regions of the gene have been associated with susceptibility to idiopathic PD in different populations. Previous studies in Japanese have found a strong association between idiopathic PD and the single-nucleotide polymorphism (SNP) rs7684318, which is located within an intron of the SNCA gene. Our aim was to verify these findings and to further explore the nature of the association in a subset of Han Chinese PD patients. A case-control study of the SNP rs7684318, comprising 332 PD patients and 300 healthy controls, was carried out in Han Chinese populations from two centers in mainland China. The rs7684318 polymorphism was determined by PCR-restriction fragment length polymorphism (PCR-RFLP) analysis. The SNP rs7684318 of the SNCA gene showed a strong association with PD (P<0.01). Among our PD patients, mean age at disease onset and gender did not differ significantly between rs7684318 carriers and non-carriers. Our findings suggested that the SNP rs7684318 (T>C) transition of the SNCA gene contributes to PD susceptibility in Chinese Han population, which is consistent with the earlier study form Japan.