Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

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<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. CONCLUSIONS: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Predictive value of ankle-brachial index for long-term events of ischemic stroke in hemodialysis patients.

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 < 0.9 was considered abnormal and 1.4 ≥ ankle-brachial index ≥ 0.9 to be normal 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 < 0.001), low seven-year averaged serum phosphate levels (HR: 0.473, 95% CI: 0.306-0.730, p = 0.001), and abnormal ankle-brachial index (HR: 0.035, 95% CI: 0.009-0.145, p < 0.001) were risk factors for ischemic stroke. In multivariate Cox regression analysis for significant variables in univariate analysis, abnormal ankle-brachial index (HR: 0.058, 95% CI: 0.012-0.279, p < 0.001) and low seven-year averaged serum phosphate levels (HR: 0.625, 95% CI: 0.404-0.968, p = 0.035) remained the risk factors for ischemic stroke. The risk of ischemic stroke was 3.783-fold in patients with abnormal ankle-brachial index compared with patients with normal ankle-brachial index (HR: 3.783, 95% CI: 1.731-8.269, p = 0.001). CONCLUSIONS: These findings suggest that ankle-brachial index is an impressive predictor of future ischemic stroke among hemodialysis patients.

Risk of Dementia in Diabetic Patients with Hyperglycemic Crisis: A Nationwide Taiwanese Population-Based Cohort Study.

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.

Disease and economic burden for rare diseases in Taiwan: A longitudinal study using Taiwan's National Health Insurance Research Database.

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.

Risk Factors for the Progression of Mild Cognitive Impairment in Different Types of Neurodegenerative Disorders.

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.

Attenuating spinal cord injury by conditioned medium from human umbilical cord blood-derived CD34⁺ cells in rats.

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 17ß-estradiol E2 (10 µg; SCI + E2), and the SCI group treated with CM plus E2 (SCI + CM + E2). 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, E2, or CM plus E2, but not by the vehicle solution. In addition, the neuroprotective effect exerted by a combination of CM and E2 is superior to that exerted by CM- or E2-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 E2 in rat SCI.

The early response of mannitol infusion in traumatic brain injury.

INTRODUCTION: Mannitol was used in traumatic brain injury but controversy about the onset and duration. SETTING: Clinical observational study. METHODS: Fourteen traumatic brain injured patients with a Glasgow Coma Scale (GCS) score < or = 8 were enrolled. Group I patients (n = 8) with intracranial pressure (ICP) < 20 mmHg, and group II patients (n = 6) with ICP > or = 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. RESULTS: The ICP declined during a 30-minute recording in both groups and the decline of ICP was significant (p < 0.05) 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 (p < 0.05) 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. CONCLUSIONS: 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 ICP > or = 20 mmHg. It demonstrated a significant dynamic difference between both groups. All these changes can be monitored by TCD and peripheral blood tests.