Teng-Fu Hsieh

Zolpidem and the risk of Parkinson's disease: A nationwide population-based study

BACKGROUND This nationwide population-based study investigated the risk of Parkinsons disease (PD) after zolpidem use in patients with sleep disturbance using the National Health Insurance Research Database (NHIRD) in Taiwan. MATERIAL AND METHODS In total, 59,548 adult patients newly diagnosed with sleep disturbance and who used zolpidem were recruited as the study cohort, along with 42,171 subjects who did not use zolpidem as a comparison cohort from 2002 to 2009. Each patient was monitored for 5 years, and those who subsequently had PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the study and comparison cohorts after adjusting for possible confounding risk factors. RESULTS The patients who received zolpidem had a higher cumulative rate of PD than those who did not receive zolpidem during the 5-year follow-up period (1.2% vs. 0.5%, P < 0.001). The adjusted hazard ratios were 1.10 (95% CI, 0.88-1.37), 1.41 (95% CI, 1.17-1.72), and 1.27 (95% CI, 1.05-1.55) for zolpidem use with 28-90, 91-365, and more than 365 cumulative defined daily doses (cDDDs), respectively, compared to those who did not use zolpidem. CONCLUSIONS Among the patients with sleep disturbance, zolpidem use increased the risk of PD after 5 years of follow-up. Further mechanistic research of zolpidem effect in PD is needed.

Use of 5-Alpha-Reductase Inhibitors Did Not Increase the Risk of Cardiovascular Diseases in Patients with Benign Prostate Hyperplasia: A Five-Year Follow-Up Study

Background This nationwide population-based study investigated the risk of cardiovascular diseases after 5-alpha-reductase inhibitor therapy for benign prostate hyperplasia (BPH) using the National Health Insurance Research Database (NHIRD) in Taiwan. Methods In total, 1,486 adult patients newly diagnosed with BPH and who used 5-alpha-reductase inhibitors were recruited as the study cohort, along with 9,995 subjects who did not use 5-alpha-reductase inhibitors as a comparison cohort from 2003 to 2008. Each patient was monitored for 5 years, and those who subsequently had cardiovascular diseases were identified. A Cox proportional hazards model was used to compare the risk of cardiovascular diseases between the study and comparison cohorts after adjusting for possible confounding risk factors. Results The patients who received 5-alpha-reductase inhibitor therapy had a lower cumulative rate of cardiovascular diseases than those who did not receive 5-alpha-reductase inhibitor therapy during the 5-year follow-up period (8.4% vs. 11.2%, P=0.003). In subgroup analysis, the 5-year cardiovascular event hazard ratio (HR) was lower among the patients older than 65 years with 91 to 365 cumulative defined daily dose (cDDD) 5-alpha-reductase inhibitor use (HR=0.63, 95% confidence interval (CI) 0.42 to 0.92; P=0.018), however there was no difference among the patients with 28 to 90 and more than 365 cDDD 5-alpha-reductase inhibitor use (HR=1.14, 95% CI 0.77 to 1.68; P=0.518 and HR=0.83, 95% CI 0.57 to 1.20; P=0.310, respectively). Conclusions 5-alpha-reductase inhibitor therapy did not increase the risk of cardiovascular events in the BPH patients in 5 years of follow-up. Further mechanistic research is needed.

Prediction of Mortality in Incident Hemodialysis Patients: A Validation and Comparison of CHADS2, CHA2DS2, and CCI Scores

Background The CHADS2 and CHA2DS2 scores are usually applied for stroke prediction in atrial fibrillation patients, and the Charlson comorbidity index (CCI) is a commonly used scale for assessing morbidity. The role in assessing mortality with score system in hemodialysis is not clear and comparisons are lacking. We aimed at evaluating CHADS2, CHA2DS2, and CCI scores to predict mortality in incident hemodialysis patients. Methods Using data from the Nation Health Insurance system of Taiwan (NHIRD) from 1 January 2005 to 31 December 2009, individuals ≧20 y/o who began hemodialysis identified by procedure code and receiving dialysis for > 3 months were included for our study. Renal transplantation patients after dialysis or PD patients were excluded. We calculated the CHADS2, CHA2DS2, and CCI score according to the ICD-9 code and categorized the patients into three groups in each system: 0–1, 2–3, over 4. A total of 3046 incident hemodialysis patients enrolled from NHIRD were examined for an association between the separate scoring systems (CHADS2, CHA2DS2, and CCI score) and mortality. Results CHADS2 and CHA2DS2 scores revealed good predictive value for total mortality (CHADS2 AUC = 0.805; CHA2DS2 AUC = 0.790). However, the CCI score did not reveal a similarly satisfying result (AUC = 0.576). Conclusions Our results show that CHADS2 and CHA2DS2 scores can be applied for mortality prediction in incident hemodialysis patients.

Association between different anticholinergic drugs and subsequent dementia risk in patients with diabetes mellitus

Background The effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with diabetes mellitus (DM) remain unknown. We investigated the effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with DM. Methods We conducted a cohort study by using the diabetes dataset of the Taiwan National Health Insurance Research Database from 1 January, 2002 to 31 December, 2013. We included 10,938 patients received one type of oxybutynin, solifenacin, or tolterodine, while 564,733 had not. We included a comparable number of patients not receiving oxybutynin, solifenacin, or tolterodine as controls through systematic random sampling matching by age, gender, and the year of the index date with 1 to 1 ratio. The dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors. Results The dementia event rates were 3.9% in the oxybutynin group, 4.3% in the solifenacin group, 2.2% in the tolterodine group and 1.2% in the control group (P<0.001). The adjusted HRs compared to nonusers of anticholinergic drugs were 2.35 (95% CI, 1.96 to 2.81), 2.16 (95% CI, 1.81 to 2.58), and 2.24 (95% CI, 1.85 to 2.73), respectively, for patients receiving oxybutynin, solifenacin, or tolterodine. Conclusion Our study indicates an association between taking oxybutynin, solifenacin and tolterodine and the subsequent diagnosis of dementia in DM patients. Moreover, the patients using oxybutynin had highest risk. The impact of these three drugs on risk of dementia in non-diabetic populations is warrant.

Relationship between Erectile Dysfunction, Comorbidity, and Parkinson's Disease: Evidence from a Population-Based Longitudinal Study.

Background and Purpose To determine the risk of Parkinsons disease (PD) in relation to erectile dysfunction (ED) based on the National Health Insurance Research Database in Taiwan. Methods We identified 3,153 patients who were newly diagnosed with ED between January 1, 2004 and December 31, 2010. A total of 12,612 randomly selected people without ED served as healthy controls. All of the study subjects were followed-up from the index date to the date of PD diagnosis, withdrawal from the National Health Insurance program, or the end of 2012 whichever occurred first. Results The incidence density rate of PD was 1.52-fold higher in the ED cohort than the non-ED cohort (3.44 vs. 1.64 per 1,000 person-years), with an adjusted hazard ratio (HR) of 1.52 [95% confidence interval (CI)=1.09–2.12]. The combined effects on patients with ED and diabetes as well as hypertension showed a significant combined association with the PD risk compared with patients without ED, counterpart comorbidities, or medication use. The adjusted HR of PD for ED was higher for diabetes (2.82, 95% CI=1.42–5.63) and hypertension (2.19, 95% CI = 1.35–3.55). Conclusions ED leads to an increased risk of PD. ED patients with diabetes or hypertension have an elevated risk of PD.

5-alpha-reductase inhibitors and the risk of diabetes mellitus: A nationwide population-based study.

This nationwide population‐based study investigated the risk of type 2 diabetes mellitus (DM) after 5‐alpha‐reductase inhibitor (5ARI) therapy for benign prostate hyperplasia (BPH) using the National Health Insurance Research Database (NHIRD) in Taiwan.

Maximum Urine Flow Rate of Less than 15ml/Sec Increasing Risk of Urine Retention and Prostate Surgery among Patients with Alpha-1 Blockers: A 10-Year Follow Up Study.

Background The aim of this study was to determine the subsequent risk of acute urine retention and prostate surgery in patients receiving alpha-1 blockers treatment and having a maximum urinary flow rate of less than 15ml/sec. Methods We identified patients who were diagnosed with benign prostate hyperplasia (BPH) and had a maximum uroflow rate of less than 15ml/sec between 1 January, 2002 to 31 December, 2011 from Taiwan’s National Health Insurance Research Database into study group (n = 303). The control cohort included four BPH/LUTS patients without 5ARI used for each study group, randomly selected from the same dataset (n = 1,212). Each patient was monitored to identify those who subsequently developed prostate surgery and acute urine retention. Results Prostate surgery and acute urine retention are detected in 5.9% of control group and 8.3% of study group during 10-year follow up. Compared with the control group, there was increase in the risk of prostate surgery and acute urine retention in the study group (HR = 1.83, 95% CI: 1.16 to 2.91) after adjusting for age, comorbidities, geographic region and socioeconomic status. Conclusions Maximum urine flow rate of less than 15ml/sec is a risk factor of urinary retention and subsequent prostate surgery in BPH patients receiving alpha-1 blocker therapy. This result can provide a reference for clinicians.

CHADS2 scores as a predictor of ischemic stroke after radical prostatectomy

Patients with prostate cancer have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. The Charlson Comorbidity Index Score (CCIS) is a widely accepted measure for risk adjustment in administrative claims data sets. This study assesses the predictive value of CHADS2 scores and CCIS for stroke among patients with prostate cancer. The study was conducted based on data taken from Taiwans National Health Insurance Research Database (NHIRD). We identified a total of 5414 participants with nonatrial fibrillation (AF) prostate cancer diagnoses who underwent radical prostatectomy between 1997 and 2011. CHADS2 scores and CCIS were used to stratify the 5‐year ischemic stroke risk. All participants were followed from the date of enrollment until ischemic stroke, death, or the end of the 5‐year follow‐up period. The 5‐year risk of ischemic stroke in the present study was 1.7%. Ischemic stroke has a better correlation with CHADS2 (CHADS2 score = 0 to 1: 0.02%, CHADS2 score = 2 to 3: 13.9%, CHADS2 score ≥ 4: 44.4%; AUC = 0.978) than CCIS (CCIS = 0 to 1: 1.6%, CCIS = 2 to 3: 1.7%, CCIS ≥ 4: 3.8%; AUC = 0.520). Our results show that patients with prostate cancer who underwent radical prostatectomy show significantly higher risk of ischemic stroke in high CHADS2 score patients, and the CHADS2 score could be applied for ischemic stroke prediction. Cardiovascular risks evaluation and management are suggested for prostate cancer patients with higher CHADS2 score.

Reply to the letter by Andrade.

Gender <0.001 Female 54,757 (62.9) 8520 (58.0) Male 32,357 (37.1) 6162 (42.0) Age 50 ± 16 55 ± 16 <0.001 Diabetes 14,982 (17.2) 3871 (26.4) <0.001 Hypertension 34,918 (40.1) 8081 (55.0) <0.001 Hyperlipidemia 22,546 (25.9) 5070 (34.5) <0.001 Anxiety 25,947 (29.8) 8049 (54.8) <0.001 Depression 12,477 (14.3) 6392 (43.5) <0.001 Alcoholism 773 (0.9) 582 (4.0) <0.001 Obesity 747 (0.9) 150 (1.0) <0.001 Bipolar disorder 1837 (2.1) 1523 (10.4) <0.001 Schizophrenia 881 (1.0) 971 (6.6) <0.001 Flurazepam 2790 (3.2) 1901 (12.9) <0.001 Triazolam 4869 (5.6) 2024 (13.8) <0.001 Drugs causing parkinsonism 58,352 (67.0) 11,577 (78.9) <0.001 Anti-psychotic medications 66,673 (76.5) 13,347 (90.9) <0.001 Socioeconomic status <0.001 Low 41,304 (47.4) 8016 (54.6) Moderate 29,900 (34.3) 4885 (33.3) High 15,910 (18.3) 1781 (12.1) Geographic Region <0.001 Northern 42,402 (48.7) 7541 (51.4) Central 18,618 (21.4) 2813 (19.2) Southern 23,759 (27.3) 3836 (26.1) Eastern 2335 (2.7) 492 (3.4)

Assessment of the charlson comorbidity index score, CHADS2 and CHA2DS2-VASc scores in predicting death in patients with thoracic empyema

Background Patients with thoracic empyema have an increased risk of mortality, but their absolute rate of mortality depends on age and comorbidities. Objective This study seeks to assess the predictive value of the Charlson Comorbidity Index score (CCIS), CHADS2 and CHA2DS2‐VASc scores for mortality risk in patients with empyema thoracis. Methods From Taiwans National Health Insurance Research Database we identified a total of 484 participants diagnosed with thoracic empyema. The CCIS, CHADS2 and CHA2DS2‐VASc scores were used to stratify mortality risk. Results The incidence rate of mortality in the present study was 20.39 per 1000 person‐months. A strong correlation was found between thoracic empyema and CCIS score. Conclusions Our results show that patients with thoracic empyema have a significantly high incidence rate of mortality and that CCIS can be used as an indicator of risk for mortality.