Nai-Fang Chi

Glaucoma, Alzheimer's Disease, and Parkinson's Disease: An 8-Year Population-Based Follow-Up Study

Background Glaucoma is the leading cause of irreversible blindness worldwide and primary open-angle glaucoma (POAG) is the most common type of glaucoma. An association between POAG and the subsequent risk of Alzheimers disease (AD) and Parkinsons disease (PD) was unclear. Objective To investigate the association between POAG (including normal-tension glaucoma) and the subsequent risk of AD or PD 8 years following a diagnosis of POAG. Methods We performed a retrospective, propensity-score-matched analysis of a population-based cohort consisting of patients with and without POAG aged 60 years and older. Control patients without POAG were propensity-score matched to POAG patients based on their baseline characteristics. Results The incidence rates and confidence intervals (CIs) of AD among the patients with and without POAG were 2.85 (95% CI: 2.19–3.70) and 1.98 (95% CI: 1.68–2.31) per 1000 person-years, respectively. The incidence rates of PD among the POAG and non-POAG cohorts were 4.36 (95% CI: 3.52–5.39) and 4.37 (95% CI: 3.92–4.86) per 1000 person-years, respectively. Kaplan-Meier failure curves showed that the POAG patients had a higher risk of AD than the control patients did (log-rank test, Pu200a=u200a.0189). However, the cumulative PD hazard ratios for the POAG and non-POAG patients did not differ significantly (log-rank test, Pu200a=u200a.9953). Conclusion In elderly patients, POAG is a significant predictor of AD, but POAG is not a predictor of PD.

Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials

PURPOSEnObstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness.nnnMETHODSnWe performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA.xa0Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on OSA published before October 2015.nnnFINDINGSnWe identified 11 RCTs of modafinil involving 723 patients and 5 RCTs of armodafinil involving 1009 patients. A pooled estimate of the mean differences in sleepiness parameters versus placebo were calculated using the random-effects model. Epworth Sleepiness Scale scores improved significantlyxa0in thexa0modafinil groupxa0(weighted mean difference [WMD],xa0-2.96 [95% confidence interval (CI), -3.73 to -2.19]) and in the armodafinil group (WMD, -2.63; 95% CI, -3.4 to -1.85) compared with those in the placebo group. Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (WMD, 2.51 [95% CI, 1.5-3.52]) and in the armodafinil group (WMD, 2.71 [95% CI, 0.04-5.37]). Patients tolerated the adverse events with both medications well.nnnIMPLICATIONSnThe findings from our study suggest that both modafinil and armodafinil significantly improved subjective and objective daytime sleepiness. Thus, modafinil and armodafinil may be recommended to patients with OSA, particularly those with EDS.

Efficacy of phenytoin, valproic acid, carbamazepine and new antiepileptic drugs on control of late-onset post-stroke epilepsy in Taiwan

To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post‐stroke epilepsy.

Epistasis analysis for estrogen metabolic and signaling pathway genes on young ischemic stroke patients.

Background Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1). Methods A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models. Results COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interactionu200a=u200a0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interactionu200a=u200a0.0174). Conclusions Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects.

Effect on Risk of Stroke and Acute Myocardial Infarction of Nonselective Nonsteroidal Anti-Inflammatory Drugs in Patients With Rheumatoid Arthritis

There are still debates on the association of increased cardiovascular risk with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA) because of inconsistent results. Therefore, our study aims to evaluate the transient effects of selective and nonselective NSAIDs on the risk of stroke and acute myocardial infarction (AMI) in patients with RA. We conducted a case-crossover study of 5,921 stroke or AMI patients with co-morbidity of RA. All cases were identified from the Taiwan National Health Insurance Database between January 1, 2006, and December 31, 2011, according to the International Classification of Diseases, 9th Revision and Clinical Modification diagnosis codes from inpatient claims. The index date was defined as the date of hospitalization for stroke or AMI. Exposure to NSAIDs was compared during a case period (1 to 30 days before the index date) with a control period (91 to 120 days before the index date). The adjusted odds ratios (ORs) of stroke and AMI were estimated using conditional logistic regression models. Our results showed that overall NSAIDs use increased the risk of stroke by 1.40-fold (95% confidence interval [CI] 1.25 to 1.56) and risk of AMI by 1.73-fold (95% CI 1.29 to 2.32). After classifying NSAIDs into selective and nonselective groups, only nonselective NSAIDs use significantly increased the risks of stroke (adjusted OR 1.39; 95% CI 1.25 to 1.55) and AMI (adjusted OR 1.82; 95% CI 1.37 to 2.41), respectively. In conclusion, nonselective NSAIDs were associated with an increased risk of both stroke and AMI in patients with RA.

Chronic obstructive pulmonary disease is associated with increased recurrent peptic ulcer bleeding risk

BACKGROUNDnThe association between chronic obstructive pulmonary disease (COPD) and the risk of recurrent peptic ulcer bleeding (PUB) remains unclear. In this study, we compared the risk of recurrent PUB between patients with and those without COPD.nnnMETHODSnUsing the Taiwan National Health Insurance Research Database, we first selected patients newly diagnosed with PUB in 2002-2009. Two groups comprising 13,732 COPD cases and 13,732 non-COPD matched controls were created using propensity score matching, thereby making the differences in basic demographics, medication use, and disease conditions between the two groups negligible. Cox proportional hazard regression was used to evaluate the risk of recurrent PUB during the follow-up period.nnnRESULTSnThe cumulative recurrence rate of PUB was significantly higher in the patients with COPD than in the non-COPD matched controls (2years: 10.8% vs 9.3%; 6years: 18.3% vs 15.7%, P all <0.05), with an adjusted hazard ratio (HR) of 1.17 (95% confidence interval [CI], 1.08-1.26, P<0.001) and 1.19 (95% CI, 1.12-1.26, P<0.001) within 2-year and 6-year follow-ups, respectively. Patients with COPD using steroids were at a marginally higher risk of recurrent PUB than those who did not use steroids. Multivariate stratified analysis revealed similar results in many subgroups.nnnCONCLUSIONSnThe risk of recurrent PUB is higher in patients with COPD than in patients without COPD.

Correction: Glaucoma, Alzheimer's Disease, and Parkinson's Disease: An 8-Year Population-Based Follow-Up Study.

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Development and validation of risk score to estimate 1-year late poststroke epilepsy risk in ischemic stroke patients

Objective This study aimed to develop and validate a prognostic model for the 1-year risk of late poststroke epilepsy (PSE). Materials and methods We included patients initially diagnosed with ischemic stroke between 2003 and 2014 in a National Health Insurance claims-based cohort in Taiwan. Patients were further divided into development and validation cohorts based on their year of stroke diagnosis. Multivariable Cox regression with backward elimination was used to analyze the association between 1-year PSE and risk factors before and on stroke admission. Results In total, 1,684 (1.93%) and 725 (1.87%) ischemic stroke patients comprising the development and validation cohorts, respectively, experienced late PSE within 1 year after stroke. Seven clinical variables were examined to be independently associated with 1-year risk of PSE. We developed a risk score called “PSEiCARe” ranging from 0 to 16 points, comprising the following factors: prolonged hospital stay (>2 weeks, 1 point), seizure on admission (6 points), elderly patients (age ≥80 years, 1 point), intensive care unit stay on admission (3 points), cognitive impairment (dementia, 2 points), atrial fibrillation (2 points), and respiratory tract infection (pneumonia) on admission (1 point). Patients were further classified into low-, medium-, high-, and very-high-risk groups. The incidence (per 100 person-years) was 0.64 (95% CI: 0.56–0.71) for the low-risk, 2.62 (95% CI: 2.43–2.82) for the medium-risk, 10.3 (95% CI: 9.48–11.3) for the high-risk, and 28.2 (95% CI: 24.0–33.0) for the very-high-risk groups. Discrimination and calibration were satisfactory, with a Harrell’s C of 0.762 in the development model and 0.792 in the validation model. Conclusion PSEiCARe is an easy-to-use prognostic score that integrates patient characteristics and clinical factors on stroke admission to predict 1-year PSE risk; it has the potential to assist individualized patient management and improve clinical practice, thereby preventing the occurrence of late PSE.