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BACKGROUND AND PURPOSE The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. METHODS This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). RESULTS Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p

Objectives The ankle–brachial index is a noninvasive modality to evaluate atherosclerosis and is a predictive role for future cardiovascular events and mortality. However, few studies have evaluated its relation to long-term future ischemic stroke in hemodialysis patients. Therefore, we examined the relationship between ankle–brachial index and ischemic stroke events among hemodialysis patients in a seven-year follow-up. Methods A total of 84 patients were enrolled. Ankle–brachial index was assessed in January 2009. Primary outcomes included ischemic stroke. An ankle–brachial index Results Mean values for ankle–brachial index were 0.98 ± 0.21at study entrance. In addition, 28 patients encountered ischemic stroke in the seven-year follow-up. In univariate Cox regression analysis, old age (hazard ratio (HR): 1.065, 95% confidence interval (CI): 1.030–1.102, p Conclusions These findings suggest that ankle–brachial index is an impressive predictor of future ischemic stroke among hemodialysis patients.

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.

Background: A hyperglycemic crisis episode (HCE) signifies poor control of diabetes and may increase the risk of dementia via microvascular and macrovascular injuries. Objectives: We conducted this study to clarify this issue, which remains unclear. Methods: Using the Taiwan National Health Insurance Database, we identified 9,466 diabetic patients with HCE and the identical number of diabetic patients without HCE who were matched by age and sex for this nationwide population-based cohort study. The risk of dementia was compared between the 2 cohorts by following up until 2014. Investigation of independent predictors of dementia was also done. Results: In the overall analysis, the risk of dementia between the 2 cohorts was not different. However, stratified analyses showed that patients with HCE had a higher risk of subsequent dementia in the age subgroup of 45−54 and 55–64 years (adjusted odds ratio [AOR]: 2.4, 95% confidence interval [CI]: 1.6–3.6, and AOR: 1.2, 95% CI: 1.0–1.5, respectively). In the overall analysis, older age, female sex, ≥3 HCEs, hypertension, hyperlipidemia, depression, cerebrovascular disease, Parkinson’s disease, and head injury were independent predictors. Conclusions: HCE increased the risk of dementia in diabetic patients aged 45–64 years. Dementia was predicted by ≥3 HCEs. Prevention of recurrent HCE, control of comorbidities, and close follow-up of cognitive decline and dementia are suggested in patients with HCE.

Background High-cost orphan drugs are becoming increasingly available to treat rare diseases that affect a relatively small population. Little attention has been given to the prevalence of rare diseases and their health-related economic burden in Taiwan. Objectives This study examined the national trends in the prevalence of rare diseases and their health-related economic burden (including medication costs) in Taiwan. Methods Rare disease-related claims data from 2003-2014 (12 years) from the National Health Insurance Research Database were used in this study. We used a time series analysis to assess trends in the yearly rates of treated patients with rare diseases, overall healthcare use, and expenditures, including drugs. Results During the 12-year study period, the estimated prevalence of rare diseases increased from 10.57 to 33.21 per 100,000 population, an average rate of a 19.46% increase per year. Total health expenditures for treatment of rare diseases increased from US$18.65 million to US$137.44 million between 2003 and 2014, accounting for 0.68% of the total national health expenditures in 2014. Drug expenditures for treatment of rare diseases increased from US$13.24 million to US$121.98 million between 2003 and 2014, which accounted for 71.00% and 88.75% of the health expenditures for patients with rare diseases in 2003 and 2014, respectively. In 2014, we found a 20.43-fold difference in average health expenditures and a 69.46-fold difference in average drug expenditures between patients with rare diseases and the overall population. Conclusions The prevalence of rare diseases and the related economic burden have grown substantially in Taiwan over the past 12 years, and these trends are likely to continue. Drug expenditures accounted for almost 90% of health expenditures for rare diseases. Further analyses are underway to examine the economic burden of individual rare diseases.

Objective. Mild cognitive impairment (MCI) is a transitional state between normal aging and early dementia. It has a heterogeneous etiology and clinical course. This study aimed to examine the factors associated with the progression of MCI in different types of dementia disorders.Method. A retrospective, longitudinal, observational study of outpatients with MCI was conducted at a medical center in northern Taiwan. Patient medical records were reviewed, and risk factors were analyzed by multivariate analysis.Results. Among 279 patients with MCI, 163 (58.4%), 68 (24.4%), and 48 (17.2%) were diagnosed with Alzheimer’s disease, vascular cognitive impairment, and Lewy body diseases, respectively. During the observation period, 37.2% of patients progressed to dementia. Older age and a higher Clinical Dementia Rating Scale-Sum of Boxes were associated with the risk of progression. Hyperlipidemia was associated with a decreased risk. Converters were more likely to receive an antidementia prescription.Conclusion. Our study suggests the importance of comprehensive clinical profiling, risk factor assessment, and detailed drug history evaluations in improving our understanding and management of dementia subtypes.

With the rapid development of electronic commerce transactions on mobile devices, achieving secure communications between communication parties is an important issue. The typical solutions are authenticated key agreement protocols, designed to efficiently implement secure channels for two or more parties communicating via a public network by providing them with a shared secret key, called a session key. In this paper, we propose two key agreement schemes based on elliptic curve cryptosystems suited for mobile environments. The first one is an identity-based remote mutual authentication with key agreement scheme, and it is used to establish a session key between the client and the server. In the second one, we extend the proposed two-party authentication key exchange scheme to develop an efficient three-party authenticated key agreement scheme for establishing a session key between two users with the help of a trusted server. Both our proposed schemes achieve efficiency, practicability, simplicity, and strong notions of security.

Yang and Chang (2009) proposed a three-party authenticated key exchange protocol for securing communications in mobile-commerce environments. Their protocol reduces computation and communication costs by employing elliptic curve cryptosystems. However, Tan (2010) pointed out that Yang and Chang (2009)’s protocol cannot withstand impersonation and parallel attacks, and further proposed an enhanced protocol to resist these attacks. This paper demonstrates that Tan (2010)’s approach still suffers from impersonation attacks, and presents an efficient and secure three-party authenticated key exchange protocol to overcome shown weaknesses.

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.

Objective Intravenous or intraspinal transplantation of human umbilical cord blood cells-derived CD34 + cells (human CD34 + cells) or mesenchymal stem cells after spinal cord injury (SCI) improved hind limb functional recovery in adult rats. The objective of this study is to ascertain whether SCI in rats can be attenuated by conditioned medium (CM) or secretome obtained from cultured human CD34 + stem cells. Materials and methods Sprague-Dawley rats were assigned to one of the following five groups: the sham group, the SCI group treated with vehicle solution (SCI + V), the SCI group treated with CM (SCI + CM), the SCI group treated with 17β-estradiol E 2 (10 μg; SCI + E 2 ), and the SCI group treated with CM plus E 2 (SCI + CM + E 2 ). A 0.5-mL volume of CM or vehicle solution was administered intravenously immediately after SCI. Results Compared with the sham group, the (SCI + V) group had significantly higher scores of neurological motor dysfunction as well as inflammation apoptosis, oxidative stress, and astrogliosis in the injured spinal cord. The neurological deficits, numbers of apoptotic cell, extent of inflammation, oxidative stress, and astrogliosis in the injured spinal cord were significantly attenuated by CM, E 2 , or CM plus E 2 , but not by the vehicle solution. In addition, the neuroprotective effect exerted by a combination of CM and E 2 is superior to that exerted by CM- or E 2 -alone therapy. Conclusion The neuroprotective effects of CM from cultured human CD34 + cells are similar to those of human CD34 + cells and the CM was found to enhance the neuroprotective effects of E 2 in rat SCI.

Mannitol was used in traumatic brain injury but controversy about the onset and duration.Clinical observational study.Fourteen traumatic brain injured patients with a Glasgow Coma Scale (GCS) scoreor = 8 were enrolled. Group I patients (n = 8) with intracranial pressure (ICP)20 mmHg, and group II patients (n = 6) with ICPor = 20 mmHg underwent transcranial Doppler (TCD) monitoring and blood samples were drawn every 5 minutes during the post-operation period. Several parameters were compared with statistical analysis between both groups.The ICP declined during a 30-minute recording in both groups and the decline of ICP was significant (p0.05) at the 10-minute interval in group II. The decline of hemoglobin (Hb) and oxygen content (CaO2), increase of venous pressure (CVP) and 02-transport ability (CeDO2) at 10-minute were also statistically significant (p0.05) in group II as compared to the group I. Using a regression model between both comparisons, several parameters were statistically different at the 10-minute interval after mannitol infusion.The dynamic responses can happen as early as 5-10 minutes after mannitol infusion, and had a greater effect on traumatic brain injury patients with ICPor = 20 mmHg. It demonstrated a significant dynamic difference between both groups. All these changes can be monitored by TCD and peripheral blood tests.

A series of 1-carbamoylmethyl-3-ethoxycarbonylmethylpyridinium salts with different anions (PF6− (1), BF4− (2), OTf− (3) and Br− (4)) have been synthesized and characterized by single-crystal X-ray diffraction. The L-shaped pyridinium cation moieties provide rich C–H donors and serve as building blocks to form grid structures with PF6− and BF4−, a zig-zag stair structure with OTf− and a bilayer structure with Br− anions.