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Hyperuricemia has been identified as an independent risk factor for coronary artery disease (CAD), with a dose-response association. In this study, we explored the causal association between gout and antigout medication and the risk of incidental CAD. We sampled data from the National Health Insurance Research Database and recruited 37,091 patients as the gout cohort, and 37,091 controls. Our primary endpoint was the diagnosis of CAD during follow-up. The overall study population was followed up until CAD diagnosis, withdrawal from the National Health Insurance program, or the end of the study. Cox proportional hazards regression models were used to examine the effect of gout on the risk of CAD, represented by the HR with the 95% CI. Patients with gout were at greater risk of CAD, compared with those without gout: HR=1.49 after adjusting for potential confounders. Non-steroidal anti-inflammatory drugs and prednisolone use was associated with a reduced risk of CAD: HR=0.63 and 0.50, respectively. Patients with gout, treated with antigout medication, exhibited a reduced risk of CAD compared with non-gout patients. Among patients with gout, those on antigout therapy had 32% lower risk compared with those not on antigout therapy: adjusted HR=0.68, 95% CI 0.63 to 0.73. Gout increases the risk of CAD, and the use of antigout medication reduces CAD risk. These results indicate that gout or hyperuricemia is a modifiable risk factor for CAD.

Background: In most countries, large cerebral artery occlusion is identified as the leading cause of disability. In 2015, five large-scale clinical trials confirmed the benefit of intra-arterial thrombectomy. However, thrombectomy is a highly technical and facility-dependent procedure. Primary stroke centers need to transfer patients to comprehensive stroke centers to perform thrombectomy. The time-lapse during interhospital transfer would decrease the chance of the patient's proper recovery. Communication barriers also contribute to this delay.Aims: We used a smartphone application to overcome communication barriers between hospitals. We aimed to shorten the door-to-puncture time of interhospital transfer patients.Methods: We began using a smartphone application, “LINE,” to facilitate interhospital communication on May 01, 2018. We carried out retrospective data analyses for all the transfer patients (n = 351), with the primary outcome being the door-to-puncture time in our comprehensive stroke center (China Medical University Hospital). We compared the three periods: May 01 to Dec 31, 2017 (before the use of the smartphone application); May 01 to Dec 31, 2018 (the 1st year of using the smartphone application); and May 01 to Dec 31, 2019 (the 2nd year of using the smartphone application). We also compared the transfer data with non-transfer thrombectomies in the same period.Results: We compared 2017, 2018, and 2019 data. The total number of transfer patients increased over the years: 63, 113, 175, respectively. The mean door-to-puncture time decreased significantly, going from 109, through 102, to 92 min. Meanwhile, the mean door-to-puncture time in non-transfer patients were 140.3, 122.1, and 129.3 min. The main reason of time saving was the change of the way of communication, from point-to-point interhospital communication to hub-to-spoke interhospital communication.Conclusions: We used this smartphone application to enhance interhospital communication, changed from the point-to-point to hub-to-spoke method. It made us overcome the communication barrier and build up interhospital connection, thus shortening the door-to-puncture time. Our experience demonstrated the importance of close communication and teamwork in hyperacute stroke care, especially in interhospital transfer for thrombectomy.

Introduction: A spinal epidural abscess is difficult to diagnose and it can sometimes mimic an acute ischemic stroke.Case presentation: We report a 69-year-old woman attended our emergency department because of gross hematuria for 1 week, with fever and bilateral flank pain. Two weeks earlier, she had received needle-knife acupotomy (a more invasive procedure than the traditional acupuncture) for chronic neck pain. Acute pyelonephritis was diagnosed; however, 4 h later, she developed weakness of both right limbs. Acute lacunar infarction was tentatively diagnosed. After admission, weakness of the left limbs developed, with a feeling of fullness and discomfort around the entire T6 dermatome with urinary retention. Neck magnetic resonance imaging showed extensive cervical epidural abscesses from C3 to T1. After an operation, her neck pain and the weakness of the four limbs gradually improved.Discussion: Spinal epidural abscess is a rare complication, and which should be considered for patients who have undergone invasive cervical procedures. Needle-knife acupotomy is a more invasive procedure than the traditional acupuncture. Conclusion: Although it is considered safe and effective for cervical spondylosis, it can be complicated by spinal infection. Careful disinfection should therefore be performed, and disposable needleknives should be used.

Background and aims Renal dysfunction is a potent risk factor for cardiovascular diseases, including stroke. This study aimed to evaluate the impact of admission estimated glomerular filtration rate (eGFR) levels on short-term (1-month) and long-term (1-year) mortality in patients with acute ischemic stroke. Methods From the Taiwan Stroke Registry data, we classified ischemic stroke patients, identified from April 2006 to December 2015, into 5 groups by eGFR at admission: ≥ 90, 60–89, 30–59, 15–29, and Results Among 52,732 ischemic stroke patients, 1480 died within one month. The 1-month mortality rate was over 5-fold greater in patients with eGFR Conclusions After acute ischemic stroke, patients with reduced eGFR are at elevated risks of short-term and long-term deaths in a graded relationship.

We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients.From the Taiwan Stroke Registry data, we identified 46,770 ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013.Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of 120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval [CI] = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of 120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively.Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or 120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.

Supplemental Digital Content is available in the text., Background and Purpose: Among patients with a transient ischemic attack or minor ischemic strokes, those with ipsilateral atherosclerotic stenosis of cervicocranial vasculature have the highest risk of recurrent vascular events. Methods: In the double-blind THALES (The Acute Stroke or Transient Ischemic Attack Treated With Ticagrelor and ASA for Prevention of Stroke and Death) trial, we randomized patients with a noncardioembolic, nonsevere ischemic stroke, or high-risk transient ischemic attack to ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2–30) or placebo added to aspirin (300–325 mg on day 1 followed by 75–100 mg daily for days 2–30) within 24 hours of symptom onset. The present paper reports a prespecified analysis in patients with and without ipsilateral, potentially causal atherosclerotic stenosis ≥30% of cervicocranial vasculature. The primary end point was time to the occurrence of stroke or death within 30 days. Results: Of 11 016 randomized patients, 2351 (21.3%) patients had an ipsilateral atherosclerotic stenosis. After 30 days, a primary end point occurred in 92/1136 (8.1%) patients with ipsilateral stenosis randomized to ticagrelor and in 132/1215 (10.9%) randomized to placebo (hazard ratio 0.73 [95% CI, 0.56–0.96], P=0.023) resulting in a number needed to treat of 34 (95% CI, 19–171). In patients without ipsilateral stenosis, the corresponding event rate was 211/4387 (4.8%) and 230/4278 (5.4%), respectively (hazard ratio, 0.89 [95% CI, 0.74–1.08]; P=0.23, Pinteraction=0.245). Severe bleeding occurred in 4 (0.4%) and 3 (0.2%) patients with ipsilateral atherosclerotic stenosis on ticagrelor and on placebo, respectively (P=NS), and in 24 (0.5%) and 4 (0.1%), respectively, in 8665 patients without ipsilateral stenosis (hazard ratio=5.87 [95% CI, 2.04–16.9], P=0.001). Conclusions: In this exploratory analysis comparing ticagrelor added to aspirin to aspirin alone, we found no treatment by ipsilateral atherosclerosis stenosis subgroup interaction but did identify a higher absolute risk and a greater absolute risk reduction of stroke or death at 30 days in patients with ipsilateral atherosclerosis stenosis than in those without. In this easily identified population, ticagrelor added to aspirin provided a clinically meaningful benefit with a number needed to treat of 34 (95% CI, 19–171). Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03354429.

Trans-cinnamaldehyde (TCA), an essential oil in cinnamon powder, may have beneficial effects as a treatment for stroke which is the second leading cause of death worldwide. Post-ischemic inflammation induces neuronal cell damage after stroke, and activation of microglia, in particular, has been thought as the main contributor of proinflammatory and neurotoxic factors. The purpose of this study was to investigate the neuroprotective effects of TCA in an animal model of ischemia/reperfusion (I/R)-induced brain injury and the neuroprotective mechanism was verified in LPS-induced inflammation of BV-2 microglial cells. Our results showed that TCA (10-30 mg/kg, p.o.) significantly reduced the infarction area, neurological deficit score and decreased iNOS and COX-2 protein expression level in I/R-induced injury brain tissue. It inhibited 0.5 µg/ml LPS-induced NO production in BV-2 microglial cells without affecting cell viability, reduced protein expression of iNOS and COX-2, and attenuated inhibition of p53 protein. TCA also suppressed the effects of LPS-induced nuclear translocation of NF-κB p65 and p50 and increased cytosolic IκBα. It also reduced LPS-induced mRNA expression of iNOS, COX-2, and TNFα. We concluded that TCA has a potential neuroprotective effect to against the ischemic stroke, which may be via the inhibition of neuroinflammation through attenuating iNOS, COX-2 expression and NF-κB signaling pathway.

Background Inflammation-related microvasculr disease, albuminuria, and rapid deterioration of renal function can accelerate the development of end-stage renal disease (ESRD). The role of hip fracture (HFr), a disorder that involves inflammation, in the development of ESRD has not been fully investigated. This study explored whether HFr increases the risk of ESRD. Methods Taiwan National Health Insurance inpatient claims were used to identify 83,550 patients newly diagnosed with HFr from 2000 to 2006, and 83,550 age- and sex-matched patients without HFr were randomly selected for comparison. Hazards of ESRD combined with HFr, comorbidities, including hypertension, hyperlipidemia, peripheral arterial disease, osteoporosis and asthma, and general health status, with Charlson comorbidity index (CCI), were assessed using data to the end of 2011. Results ESRD risk was 1.42-fold higher (95% confidence interval [CI]:1.29–1.33) in the HFr cohort than in the control group, which was computed using the Cox proportional model. Age-specific analysis revealed that the adjusted hazard ratios (aHRs) of ESRD for HFr patients increased slightly as age increased, with an aHR of 1.56 (95% CI:1.35–1.81) for patients 65–74 years old, which gradually decreased to 0.88 (95% CI:0.66–1.18) for patients ≥ 85 years old. ESRD risk increased as HFr severity increased, with an aHR of 6.71 (95% CI:5.90–7.63) for patients with severe HFr. Conclusion This study is the first to report that HFr, in combination with underlying osteoporosis-related chronic illness, microvascular disease and chronic inflammation, is associated with an increased risk of ESRD, particularly among relatively younger people.

Summary Purpose Inflammatory processes, which raise the unsteadiness of brain neuron membrane potentials, might enhance the development of epilepsy. Inflammation is a substantial indicator of epilepsy risk. In this study, we evaluated whether chronic osteomyelitis (COM), a chronic inflammatory disease, increases epilepsy risk. Materials and methods A Taiwanese national insurance claims dataset of more than 22 million enrollees was used to select 20,996 COM patients and 83,973 randomly selected age- and gender-matched controls to investigate epilepsy development over an 11-year follow-up period, starting on January 1, 2000 and ending on December 31, 2010. The epilepsy risk was analyzed using a Cox proportional hazards regression model. Results Comorbidities known to elevate epilepsy risk, including diabetes, hypertension, head injury, stroke, and cancer, were commonly noted in the COM cohort, which had considerably higher risk of epilepsy than did the control group. Comparing only those without comorbidities, COM patients still exhibited higher epilepsy risk than the control group did (adjusted hazard ratio [aHR] = 3.87, 95% confidence interval [CI]: 3.01–4.98). The younger population exhibited an even greater risk (age ≤39 years: aHR = 6.10, 95% CI: 4.00–9.30; age ≥65 years: aHR = 1.66, 95% CI: 1.28–2.16). Conclusion This is the first study linking COM to an increased risk in epilepsy development. The results demonstrated that COM is a significant predictor of epilepsy. Further study of COM patients, particularly young patients, is recommended to facilitate epilepsy prevention.

Inflammatory processes may trigger neuroinflam- mation and cerebrovascular dysfunctions, further provoking dementia.Theroleofchronicosteomyelitis(COM),adisorder characterized by persistent inflammation, in dementia devel- opment has not been fully explored. This study investigates whether COM increases the risk of dementia. Taiwanese National Health Insurance (NHI) inpatient claims were used to identify 17,238 patients newly diagnosed with COM from 2000 to 2008, and 68,944 age- and gender-matched patients without COM were randomly selected for comparison. Risks of dementia associated with COM and comorbidities, includ- ing hypertension, diabetes, stroke, hyperlipidemia, and de- pression, were evaluated using data from the end of 2011. Dementia risk was 1.6-fold higher (95 % confidence interval (CI): 1.4-1.83) in the COM cohort than in the control group, calculated using the multivariable Cox model. Age-specific analysis indicated that the adjusted hazard ratios (aHRs) of dementia for COM patients decreased with age, with an aHR of 3.65 (95 % CI: 1.5-8.9) for patients

Background and aims This cohort study assessed the association between inflammatory bowel disease (IBD) and the risk of future ischemic stroke. Methods The IBD cohort comprised adult patients (≥ 20 years old) who had received either ambulatory or inpatient care between 1998 and 2011 and IBD-free controls were randomly selected from the general population and frequency matched according to age, sex, and index year (included 18,392 patients with IBD and 73,568 control patients). Both cohorts with ischemic stroke before the index date and the ischemic stroke cases diagnosed within one year after the index date were excluded. We observed the study patients until the incidence of ischemic stroke, death, withdrawal from the insurance program, or they were lost to follow-up, or the end of 2011. Results The risk of ischemic stroke was 1.12-fold (95% CI, 1.02–1.23) higher among the IBD cohort than among the non-IBD cohort. Compared to the subjects without IBD, the adjusted HR of ischemic stroke was 1.15 (95% CI 1.04–1.28) in the Crohn's disease (CD) patients and 1.01 (95% CI 0.84–1.21) in the ulcerative colitis (UC) group. The risk of developing ischemic stroke significantly increased with the increased frequency of IBD exacerbation and hospitalization. Furthermore, the adjusted HR among the CD patients increased in conjunction with the number of medical visits, from 1.07 to 6.36 and the adjusted HR among the UC patients also increased in conjunction with the number of medical visits, from 1.11 to 2.10. Conclusions IBD exhibited an increased risk of developing ischemic stroke.

Background: Paeoniflorin (PF) possesses several effects such as analgesic, the anti-spasmodic effect on smooth muscle. It protects the cardiovascular system and reveals the neuroprotective effect on cerebral ischemia. Monoamine system has been identified to have complex regulatory effects in pain signaling. There are no reports regarding the impact of PF on monoamine levels in the rodent brain by microdialysis. In this study, the effects of PF on monoamines and their metabolites in the rodent brain using in vivo microdialysis and in vitro high performance liquid chromatography (HPLC) analysis. Methods: Male S.D. rats were anesthetized, fixed onto the stereotaxic instrument to identify the positions of corpus striatum and cerebral cortex. Drilled a hole in the skull of anesthetic rats and proceeded microdialysis, and gave PF (100 μg, i.c.v.). Collected the dialysate and the concentration of monoamines and their metabolites in dialysate and analyzed with HPLC-ECD. Male ICR mice were administered with PF (96 μg, i.c.v.) and with Ringer solution as a control. After 20 mins of administration, the mice were cut off the brain immediately and separated into eight regions according to the method of Glowinski. Added extraction solution to each region, homogenized and extracted for further procedure. The extract was centrifuged, sucked the transparent layer and centrifuged once more. The transparent layer was filtered with a 0.22 μm nylon filter and analyzed with HPLC-ECD (electrochemical detection). Results: PF increased the content of DOPAC and NE in the cortex, and increased the content of NE and decreased the content of 5-HT in the medulla of the homogenized mice brain tissue. By microdialysis, PF increased the content of DOPAC and 5-HIAA in anesthetic rat cortex and expanded the content of DOPAC, HVA, and 5-HIAA in anesthetic rat striatum. Conclusions: It reveals that PF could activate the release of monoamines and increase their metabolites in the rodent brain.

Background/Aims: We investigated the association of hypertensive encephalopathy (HE) with subsequent dementia. Methods: Using universal insurance claims data, we identified a study cohort of 5,504 participants with HE newly diagnosed between 1997 and 2010 and a comparison cohort of 22,016 healthy participants. Incidence and risks of dementia were estimated for both cohorts until the end of 2010. Results: The dementia incidence was 1.45-fold [95% confidence interval (CI) = 1.27-1.66] higher in the study cohort than in the comparison cohort, with an adjusted hazard ratio (HR) of 1.38 (95% CI = 1.19-1.59) for the study cohort. The risk was higher for males than for females and elderly patients. With an incidence of 13.4 per 1,000 person-years, the HR of dementia increased to 2.09 (95% CI = 1.18-3.71) for the HE patients with the comorbidities of head injury and diabetes compared to those without HE and comorbidities. The risk of developing dementia declined with the follow-up time. Conclusion: Hypertensive patients with HE displayed a significantly higher risk for dementia than those without HE. The risk increased further in those with the comorbidities of head injury and diabetes. Physicians should be aware of the link between HE and dementia when assessing patients with HE.

Aim The aim of this study was to investigate the possible association between benzodiazepine (BZD) use and risk of incident stroke by utilizing data from 2000 to 2003 from the National Health Insurance system of Taiwan. Methods Study subjects consisted of 38 671 patients with new BZD use and 38 663 people without BZD use who were frequency-matched for age, sex and baseline comorbidity with BZD users. All subjects had no history of stroke. Each study patient's case was followed until a new diagnosis of stroke was made or until the patient was censored by loss to follow up, death, or termination of insurance. The study lasted until the end of 2009. A Cox proportional hazards regression model was used to estimate the incidences and hazard ratios (HR) of stroke. Results The HR of hemorrhagic stroke was significantly lower in the BZD group when compared with the non-BZD group. For patients aged 20–39 years, the HR of ischemic stroke was significantly higher in the BZD group when compared with the non-BZD group. Compared to the non-BZD group, patients with a lower annual dosage (

Background: Risks of stroke link with complications of hyperglycemia. Gueichih-Fuling-Wan (GFW), according to Chinese Medical Code literature, has the promotion of blood circulation and attenuates the swollen plot. Recent pharmacological studies have pointed out its efficacy in patients with cerebral ischemia or diabetes. Therefore, this study determined whether GFW has the protection against cerebral ischemia/ reperfusion (I/R) injury in streptozotocin (STZ)-induced hyperglycemic rats and LPS-induced inflammation in BV-2 microglial cells. Methods: Extracts of GFW were filtered and frozen to dry for use. Hyperglycemia was induced by intraperitoneal injection of 70 mg/kg STZ. Fourteen days after STZ injection, GFW (1, 2 and 4 g/kg) was orally administered once daily for seven days. Rats were subjected to cerebral ischemia/reperfusion and sacrificed for infarction analysis and neuronal apoptosis detection twenty-one days after STZ injection. MTT assay was used for cell viability; nitrite quantification and western blot analysis of iNOS and COX-2 were used to explore the effects of GFW on LPS-induced inflammation in BV-2 microglial cells. Results: GFW significantly ameliorated cerebral infarction while dosage was more than 1 g/kg (by 38.03% at 2 g/kg and 52.44% at 4 g/kg), and attenuated neurological deficits by 23.48% (at 2 g/kg) and 47.25% (at 4 g/kg). Furthermore, GFW (2, 4 g/kg) notably decreased TUNEL- and cleaved caspase-3-positive cells in the immunohistochemical stain (P < 0.01 and P < 0.001, respectively). GFW remarkably increased in Bcl-2 and decreased in caspase-3 and Bax/Bcl-2 ratio protein expressions by Western blot. GFW (0.25, 0.5, 1 mg/ ml) significantly reduced LPS-induced NO production in BV-2 microglial cells. And GFW attenuated iNOS and COX-2 expression in LPS-treated BV-2 cells. Conclusions: In summary, GFW has good bioactivities to protect cerebral I/R injury in hyperglycemic rats, which might be due to inhibition of cellular apoptosis and neuroinflammation.

Background and purpose Astragalus membranaceus (AM) is the first-choice herb for fatigue treatment in traditional Chinese medicine and the main herb used for stroke treatment in China and Taiwan. The purpose of this study was to evaluate the effect of AM on poststroke fatigue (PSF). Materials and methods This study was designed as a double-blind, randomized, controlled preliminary study. Sixty-four patients with PSF were assigned to treatment group (TG; 31 patients), which received oral administration of AM (2.8 g three times per day) for 28 days, and a control group (CG; 33 patients), which received a placebo. The primary outcome measures were the changes in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and Brief Fatigue Index (BFI) scores Results A total of 61 patients (29 patients in the TG and 32 patients in the CG) completed the trial. The difference in BFI scores between Visit 2 and Visit 1 was –17.83±17.70 in the TG, which was greater than that in the CG (–8.03±9.95; p=0.01); additionally, the difference in BFI scores between Visit 3 and Visit 1 was –16.48±16.41 in the TG, which was also greater than that in the CG (–9.47±13.39; p=0.05). In the EORTC QLQ-C30, the difference in cognitive functioning scores between Visit 2 and Visit 1 was 14.37±13.89 in the TG, which was greater than that in the CG (3.65±19.74; p=0.02); additionally, the difference in these scores between Visit 3 and Visit 1 was 14.37±16.50 in the TG, which again was greater than that in the CG (6.25±19.74; p=0.04). The difference in social functioning scores between Visit 3 and Visit 1 was 9.77±15.12 in the TG, which was greater than that in the CG (–1.56±20.46; p=0.01). The difference in global quality of life (QOL) scores between Visit 2 and Visit 1 was 14.08±18.78 in the TG, which was also greater than that in the CG (1.56±18.14; p=0.003); moreover, the difference in these scores between Visit 3 and Visit 1 was 10.92±17.55 in the TG, and this was greater than that in the CG (1.82±15.8; p=0.05). Conclusion AM can improve BFI scores; cognitive functioning, social functioning, and global QOL scores in the EORTC QLQ-C30. Our results suggest that physicians should pay close attention to the unmet medical needs of patients with PSF. AM is helpful for treating patients with PSF; however, additional studies with a larger sample and a longer period of investigation are required.

Botulism is a rare but serious paralytic disease caused by botulinum toxin. We report an outbreak of type B botulism in Taiwan in 2006. There were five cases involved in this outbreak. They present ileus and acute cranial nerve dysfunction including dysphagia and blurred vision. One of them had severe neurologic impairment and required mechanical ventilatory support. No patient received antitoxin administration because of delayed diagnosis. The food specimen revealed positive botulism toxin B. There were no fatalities. Consumption of fermented food was significantly associated with this outbreak. We also reviewed the characteristics of cases with botulism in Taiwan since 1985.

Objective Movement-related cortical potentials (MRCP; nomenclature of MRCP components according to Shibasaki and Hallett (Shibasaki H, Hallett M. What is the Bereitschaftspotential? Clin Neurophysiol 2006;117:2341–56) were studied in patients with Machado–Joseph disease (MJD) to elucidate the pathophysiology of voluntary movement. Methods We studied nine genetically proven MJD patients and eight age-matched healthy subjects. Multi-channel electroencephalogram (EEG) recordings were obtained during self-paced fast extensions of the wrist. EEG epochs were time-locked to electromyography (EMG) onset or offset of the voluntary EMG burst and averaged. Results In the MJD patients, the early Bereitschaftspotential (early BP, −1500 to −500 ms) was not affected but the late BP was reduced over the central midline area and contralaterally to the movement side. The amplitude of the fpMP, a post-movement MRCP component, was also reduced. In addition, the offset cortical potential in the first 500 ms after EMG offset (Moff + 500) was attenuated bilaterally over a wide cortical area. Conclusions Findings suggest that cortical activations associated with the initiation and termination of a voluntary movement are impaired in MJD patients. Significance Abnormalities of pre- and post-movement MRCP components provide researchers with pathophysiological insight into voluntary motor dysfunction in MJD.

OBJECT Inflammation may provoke cerebral arteriolar ectasia, inducing microaneurysm formation and further promoting intracerebral hemorrhage (ICH). Chronic osteomyelitis (COM) is an inflammatory disorder for which study of its role in ICH is lacking. This study explored whether COM increases the risk of ICH. METHODS From Taiwan national insurance inpatient claims, 22,052 patients who were newly diagnosed with COM between 1997 and 2010 were identified; 88, 207 age and sex frequency-matched subjects without COM were selected at random for comparison. Risks of ICH associated with COM and comorbidities, including hypertension, diabetes, hyperlipidemia, chronic kidney disease, and drug abuse, were assessed by the end of 2010. RESULTS The incidence of ICH was 1.68 times higher in the COM cohort than in the comparison cohort, with an adjusted hazard ratio (HR) of 1.50 (95% CI 1.29–1.74) estimated in the multivariable Cox model. Age-specific analysis showed that the HR of ICH for COM patients decreased with age, with an adjusted HR of 3.28 (95% CI 1.88–5.75) in the < 40-year age group, which declined to 1.11 (95% CI 0.88–1.40) in the elderly. The incidence of ICH increased with the severity of COM; for those with severe COM the adjusted HR was 4.42 (95% CI 3.31–5.89). For subjects without comorbidities, the incidence of ICH was 1.20-fold (95% CI 1.00–1.45) higher in the COM cohort than in the comparison cohort. CONCLUSIONS This study suggests for the first time that COM is an inflammatory factor associated with increased risk of ICH, especially in younger patients.

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 32 female patients with primary Sjögren's syndrome (PSS) showing definite neuropsychiatric symptoms/signs and normal brain magnetic resonance imaging (MRI) findings. It demonstrated hypoperfusion brain lesions in 18 (56.3%) of the patients, most frequently in the parietal lobes, and appears to be a sensitive tool for this clinical application.

Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval [CI], .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.

Background and purpose: The association of Helicobacter pylori infection ( HP- I) with ischemic stroke (IS) incidence has been studied, but conflicting results have been reported. The purpose of this study was to investigate the association between chronic HP- I and the risk of acute IS by using data from the Taiwan National Health Insurance Research Database. Methods: We identified17 332 patients with HP- I and 69 328 randomly selected age- and gender-matched controls from 1 January 2000 to 31 December 2010. Both cohorts were followed up until the occurrence of IS or until censored. The Cox proportional hazards model was used for assessing the association of HP- I with IS. Results: Compared with the control cohort, patients diagnosed with HP- I exhibited a higher incidence rate of IS (14.8 vs. 8.45 per 1000 person years) and a hazard ratio (HR) of 1.52 (95% confidence interval [CI] = 1.40–1.65). The HRs for IS were 1.49 (1.37–1.62) in patients diagnosed with HP- I who had one admission, increasing to 2.26 (1.71–1.98) for those who had two or more admissions when adjusted for age, sex and comorbidities ( P for trend < 0.0001). In addition, we observed a significantly positive association between nonembolic IS and increased admissions ( P for trend < 0.0001) but negative association with embolic IS. Conclusion: Chronic HP- I is significantly associated with an increased risk of IS, particularly nonembolic IS. Anti- HP therapy may be beneficial to IS prevention.

The aim of this study was to investigate the possible association between benzodiazepine (BZD) use and risk of incident stroke by utilizing data from 2000 to 2003 from the National Health Insurance system of Taiwan.Study subjects consisted of 38,671 patients with new BZD use and 38,663 people without BZD use who were frequency-matched for age, sex and baseline comorbidity with BZD users. All subjects had no history of stroke. Each study patient's case was followed until a new diagnosis of stroke was made or until the patient was censored by loss to follow up, death, or termination of insurance. The study lasted until the end of 2009. A Cox proportional hazards regression model was used to estimate the incidences and hazard ratios (HR) of stroke.The HR of hemorrhagic stroke was significantly lower in the BZD group when compared with the non-BZD group. For patients aged 20-39 years, the HR of ischemic stroke was significantly higher in the BZD group when compared with the non-BZD group. Compared to the non-BZD group, patients with a lower annual dosage (1 g) or duration (30 days) of BZD use had a lower risk of stroke in the elder group (P 0.0001) and patients with a higher annual dosage (≥ 4 g) or duration (≥ 95 days) of BZD use had a higher risk of stroke in all age groups (P 0.0001).Our findings may suggest neuroprotection under lower-dosage BZD use and neurotoxicity under higher-dosage BZD use.

Objective Inflammatory processes, which provoke alternations of neurotransmitter metabolism, neuroendocrine function, and neuroplasticity in the brain, might promote depression. In depression patients who do not exhibit risk factors, including hypertension, diabetes, coronary heart disease, stroke, Parkinson's disease and dementia, particularly in young people, inflammation is a likely risk factor for depression. We explored whether chronic osteomyelitis (COM), a chronic inflammatory disease, increases depression risk. Methods A Taiwanese national insurance claims data set of more than 22 million enrollees was used to select 15,529 COM patients without depression history and 62,116 randomly selected age- and gender-matched controls without depression and COM history to trace depression development for an 12-year follow-up period from January 1, 1999 to December 31, 2010. The depression risk was analyzed using the Cox proportional hazards regression model. Results The above-mentioned risk factors for depression were more frequent in the COM cohort, who exhibited significantly higher depression risk than the control group did. Comparing only those without comorbidities, the COM group exhibited higher depression risk than the control group did (hazard ratio [HR] = 3.04, 95% confidence interval [CI]: 2.55–3.62). The younger population carried even greater risk (age 65: HR = 1.75, 95% CI: 1.39–2.19). Conclusions This is the first study connecting COM to increased risk of developing depression. The outcomes suggest that COM is a substantial depression predictor and call for a closer focus on these patients for more rigorous depression prevention, particularly in young people.

Dementia is the severe loss of global cognitive ability in a previously healthy person. This study examined the relationship between Helicobacter pylori infection (HP-I) and non-Alzheimer's dementia (non-AD) using a nationwide population-based dataset. The International Classification of Diseases, Ninth Revision (ICD-9) codes for dementia were used to define dementia patients; in addition, we examined the association of dementia with other comorbidities. Patients aged ≥40years with newly diagnosed HP-I (ICD-9 code 041.86) during 1998-2010 were identified as the HP-I cohort. The comparison cohort consisted of people aged ≥40years without HP-I (non-HP-I) randomly selected from the database at a ratio of 1:4 in the same time period. The controls were frequency matched according to the age (every 5years), sex, and index year of patients in the HP-I cohort. Follow-up was performed for all patients until the date of dementia diagnosis (ICD-9 codes 290.0-290.4, 294.1, 331.0-331.2), date of withdrawal from the Taiwanese National Health Insurance program, date of death, or until December 31 2010. Compared with patients without HP-I, HP-I patients were 1.60-fold (95% confidence interval [CI] 1.32-1.95) more likely to develop non-AD. There was no statistical association between HP-I and AD. The adjusted hazard ratio of dementia increased from 1.48 (95% CI 1.22-1.79) for patients who had HP-I once to 2.19 (95% CI 1.13-4.25) for patients who had HP-I two or more times. Our study revealed that HP-I may be a critical risk factor for the development of non-AD. Further investigation, including clinical trials, to examine the microbe-dementia connection may provide further proof of the association between HP-I and dementia.

Background and objectives Obstructive sleep apnea (OSA) is related to an increased risk for stroke and cardiovascular disease. However, studies investigating the relationship between nonapnea sleep disorders (NSD) and the risk for subsequent ischemic stroke are scant. The objective of our study was to assess the association between NSD and the risk for acute ischemic stroke among patients in Taiwan. Methods We conducted our longitudinal nationwide, population-based, retrospective study using Taiwan’s National Health Insurance Research Database (NHIRD) from January 1997 to December 2001. All study participants were followed until the incidence of ischemic stroke, or until censoring due to death; until withdrawal from the insurance program; or until they were lost to follow-up by the end of 2010. Cox proportional hazard regression analysis was used to assess the association between NSD and subsequent ischemic stroke risk. Results We analyzed the data collected from 94,160 participants as a comparison cohort and 47,080 participants as a NSD cohort with the diagnosis date as the index date. The age range of cohorts was 20.0–101.7 years and 64% were women. The average follow-up duration was 9.61 years for the NSD cohort and 9.42 years for the reference cohort. Overall, the ischemic stroke incidence was 1.48-fold higher in the NSD cohort than in the reference cohort (8.87 vs 6.00/1000 individual-years), with an adjusted hazard ratio (HR) of 1.19 after controlling for age, sex, and comorbidities. Our study also showed a 1.35-fold significantly higher risk for developing ischemic stroke in men compared to women. The adjusted HR was 31.2 for elderly patients compared with participants aged ⩽35 years. Conclusions Our nationwide, population-based, retrospective cohort study provides evidence that patients with NSD were at increased risk for developing ischemic stroke compared to patients without diagnosed sleep disorder, with men and the elderly being at greatest risk.

OBJECTIVE To evaluate the relationship between the use of zolpidem and risk of subsequent stroke in Taiwanese patients. METHOD This case-control study used data obtained from the National Health Insurance Research Database to determine whether the use of zolpidem is associated with an increased risk of stroke. The case group comprised 12,747 patients who were newly diagnosed with stroke between January 1, 2005, and December 31, 2009. We also randomly selected a 4-fold greater number of patients without stroke as a control group. Patients with ischemic and hemorrhagic stroke were frequency-matched with controls on sex, age, and year of index date. We measured the effect of zolpidem and determined the adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS We found that exposure to zolpidem was associated with increased risk of ischemic stroke (OR = 1.37; 95% CI, 1.30-1.44). The risk of ischemic stroke increased significantly with increasing exposure to zolpidem; for average exposures of ≤ 70, 71-470, and > 470 mg per year, the ORs were 1.20, 1.41, and 1.50, respectively; the P value for the trend was < .0001. Regardless of whether people presented with a sleep disorder, the risk of stroke was still greatly increased with zolpidem exposure; the adjusted OR was 1.37 without sleep disorder and 1.41 with sleep disorder. CONCLUSIONS This population-based study positively associated the use of zolpidem with increased risk of ischemic stroke. Our findings warrant further large-scale and in-depth investigations in this area.

To identify the possible anatomic sites and risk factors for the development of confusion or delirium in patients with posterior cerebral arterial (PCA) infarction.Twenty-nine patients aged 34-86 years with PCA infarction were divided into two groups: one with and the other without perturbed mentation. The clinical and laboratory data, including neuroimages, were retrospectively reviewed. Student-t, chi-square and Fisher's exact tests were performed for data analysis.Confusion or delirium tended to develop in the left (10/13) or bilateral (5/5) PCA infarction as compared to the right PCA infarction (3/15) (P0.05) and medial occipital-temporal gyri involvement was crucial for its development (P0.05). The results were also noted in the patients with first-ever stroke. Diabetes mellitus was the sole biochemical factor to be associated with confusion or delirium (P0.01).The involvement of the medial occipito-temporal gyri, especially on the left side was the pivotal factor for the development of confusion or delirium in patients with PCA infarction. Higher prevalence of diabetes mellitus was also observed in the group with mental perturbation.

We report the clinical features and dopamine transporter [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo[3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl]amino]ethanethiolato(3-)-N2,N20,S2,S20]oxo-[1R-(exo-exo)]-[99mTc] technetium([99mTc]TRODAT-1) image finding in an 86-year-old woman with akinetic mutism due to infarction of bilateral anterior cerebral arterial territories. TRODAT-1 is a cocaine analogue that can be labeled with technetium-99m and bound to the dopamine transporter (DAT) site. It reflects primarily the integrity of presynaptic dopamine neuron terminals. With the evolution of the clinical features, the TRODAT SPECT images change from bilateral diminution of radioactivity uptake at the 81st-day check point to normal pattern at the 6-month one when the akinetic mute manifestations were nearly gone. This novel illustration suggests that the akinetic mutism caused by anterior cerebral arterial infarct is closely linked to the perturbation of the subcortical dopaminergic system. And the amelioration of the clinical features concordantly evolved with the restoration of the dopaminergic function.

99mTc ethyl cysteinate dimer ( 99m Tc-ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in patients with acute carbon monoxide (CO) poisoning. Ten patients with acute CO poisoning and no past histories of psychoneurological disorders were enrolled in this study. After oxygen treatment, all of the 10 patients were investigated using 99m Tc-ECD brain SPECT and brain computed tomography (CT) scan. Brain CT scan findings were normal in all of the 10 patients. 99m Tc-ECD brain SPECT showed the hypoperfusion lesions of the basal ganglia and brain cortex in five and seven patients, respectively. Only three of the 10 patients had normal 99m Tc-ECD brain SPECT findings. This study suggests that, in comparison with brain CT scan, 99m Tc-ECD brain SPECT is a better tool for the early detection of hypoperfusion brain lesions in acute CO poisoning in patients with normal brain CT findings.

Involvement of the brain is one of the most important complications of Behcet's disease, but its diagnosis is difficult because of the lack of effective imaging tools. Therefore, technetium-99m ethyl cysteinate dimer (Tc-99m ECD) single-photon emission computed tomography (SPECT) of the brain was used to detect abnormal regional cerebral blood flow in patients with neuro-Behcet's syndrome (NBS). Tc-99m ECD brain SPECT was per-formed to detect hypoperfusion areas of the brain in 10 NBS patients with definite neuropsychiatric symptoms or signs and normal brain magnetic resonance imaging (MRI) findings. Tc-99m ECD brain SPECT demonstrated hypoperfusion areas of the brain in all of the 10 NBS patients. The parietal lobes were the most common areas with hypoperfusion lesions. Tc-99m ECD brain SPECT is a more sensitive and useful tool than brain MRI for detecting hypoperfusion areas of the brain in NBS patients.

Technetium-99m ethyl cysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) was used to detect abnormal regional cerebral blood flow (rCBF) in 78 SLE patients with neuropsychiatric manifestations. These patients were separated into two subgroups: group 1 including 48 cases with definite neuropsychiatric symptoms/signs and group 2 with 30 cases having no neuropsychiatric symptoms/signs. Tc-99m ECD brain SPECT demonstrated hypoperfusion brain lesions in 90% and 20% of patients in groups 1 and 2, respectively. In both groups, parietal lobe and cerebellum are the most and least common areas with hypoperfusion lesions, respectively. This study suggests that Tc-99m ECD brain SPECT may provide objective information for detection of hypoperfusion brain lesions in SLE patients.