Association of Angiotensin Receptor Blockers with Incident Parkinson Disease in Patients with Hypertension: A Retrospective Cohort Study.

BACKGROUND: Angiotensin receptor blockers (ARBs), which are commonly used antihypertensives, have been proposed to lower the risk of Parkinson disease by reducing oxidative stress based on animal and in vitro studies. Thus, this study aimed to test this association in patients with newly diagnosed hypertension. METHODS: This retrospective cohort study enrolled 107,207 patients with newly diagnosed hypertension between 2001 and 2013. The hazard ratios for Parkinson disease were calculated for ARB treatment compared with those who never used ARBs and among the 5 subgroups receiving different cumulative ARB dosages. RESULTS: We identified 527 (1.1%) Parkinson disease cases among patients with ARB treatment in a median observation period of 8.4 years compared to the 1,255 (2.2%) Parkinson disease cases among those without ARB treatment in a median observation period of 6.8 years. Overall, risk for developing Parkinson disease was statistically lower in the ARB-treated group with a hazard ratio of 0.56 (95% confidence interval: 0.51-0.63) than those without ARB. CONCLUSIONS: ARB treatment was associated with a statistically important reduction of Parkinson disease risk in patients with newly diagnosed hypertension. Therefore, ARB may constitute an effective neuroprotective strategy to lower Parkinson disease risk in such patients.

Calcium Channel blockers are associated with reduced risk of Parkinson's disease in patients with hypertension: A population-based retrospective cohort study.

BACKGROUND: The use of dihydropyridine calcium channel blockers (DCCBs) was proposed to reduce the risk of Parkinson's disease (PD). This study aimed to evaluate the association between DCCB and its dose effect and the risk of PD in patients with newly diagnosed hypertension. METHODS: This population-based retrospective cohort study enrolled 107,207 patients with newly diagnosed hypertension, between 2001 and 2013, from Taiwan's National Health Insurance Research Database. Patients who had PD before hypertension or were taking antipsychotics for more than 30 days in the 6 months prior to the end of the observation period were excluded. A Cox proportional hazard model was used to estimate the risk of PD in different groups. The dose-related effects of DCCB on the risk of PD were evaluated according to the cumulative defined daily dose (DDD). RESULTS: We observed 832 (1.2%) PD cases in patients treated with DCCB as compared to 950 (2.4%) PD cases in those not treated with DCCB, during a median follow-up duration of 8.3 years and 6.2 years, respectively. The risk of PD in the DCCB-treated group (hazard ratio [HR] = 0.50) was significantly lower than that in the group without DCCB treatment. DCCB reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.61 to 0.37 for DDDs of 90-180 to >720. CONCLUSIONS: DCCB treatment was associated with a significantly reduced risk of PD in patients with newly diagnosed hypertension. Further clinical trials are needed to confirm the proposed neuroprotective effects of DCCB in PD.

Urinary tract infection is associated with hypokalemia: a case control study.

BACKGROUND: Hypokalemia is a common clinical problem. The association between urinary tract infection (UTI) and hypokalemia is not clear. Hypokalemia is common in patients with UTI in clinical observation. The aim of the study is to determine if UTI is associated with hypokalemia. METHODS: Patients hospitalized with UTI and the control group were retrieved from the Longitudinal Health Insurance Database 2005. The control group was patients hospitalized with other reasons and were matched for the confoundings of UTI and hypokalemia. We analyze the risk of hypokalemia using logistic regression and calculate the odds ratio (OR) and 95% confidence interval (CI) of OR. RESULTS: We analyzed 43,719 UTI patients and control patients. Hypokalemia was found in 4540 (10.4%) patients with UTI and 1842 (4.2%) control patients. The percentage of patients with hypokalemia was higher in UTI patients (chi-square, p < 0.001). UTI was associated with hypokalemia and the odds ratio (OR) was 2.27 [95% confidence interval (CI): 2.17-2.41]. Cerebrovascular accident, chronic obstructive pulmonary disease, hypertension, congestive heart failure, diarrhea, medications including thiazides, sulfonamides, xanthines, and laxatives were independently associated with hypokalemia. Recurrent UTI was associated with hypokalemia in UTI patients (OR: 1.13, 95% CI: 1.05-1.23, p < 0.001). CONCLUSIONS: Urinary tract infection is associated with hypokalemia among inpatients. The association is independent of patients' comorbidities and medications. Recurrent UTI is associated with increased hypokalemia in UTI patients.

Association of thiazolidinedione with a lower risk of Parkinson's disease in a population with newly-diagnosed diabetes mellitus.

OBJECTIVES: We investigated the association of thiazolidinedione and its dose effect with the risk of Parkinson's disease (PD) in patients with diabetes mellitus (DM). METHODS: This study enrolled 38,521 patients with newly-diagnosed DM, between 2001 and 2013, and compared them to the matched subjects without DM. The hazard ratios (HRs) for PD were compared between the thiazolidinedione-treated and non-thiazolidinedione-treated groups of the study cohort, and between subgroups who received different cumulative dosages of thiazolidinedione. RESULTS: We observed that 544 (1.4%) patients developed PD during the follow-up median duration of 6.2 years in patients with newly-diagnosed DM or had a higher risk for PD than patients without DM (HR = 1.150). In the study cohort, the risk of PD was significantly lower in the thiazolidinedione-treated group (HR = 0.399) compared to the non-thiazolidinedione-treated group. Thiazolidinedione reduced the risk of PD in a dose-dependent manner, with HRs ranging from 0.613 to 0.081 with defined daily doses of 0-90 to >720, respectively. CONCLUSIONS: Thiazolidinedione use was associated with a significantly reduced risk of PD in patients with newly-diagnosed DM. Further studies to elucidate the common mechanism of PD and DM may provide novel therapies for these two diseases. Key messages Newly-diagnosed diabetes mellitus slightly increases the risk for Parkinson's disease. Thiazolidinedione is associated with a lower risk of Parkinson's disease in a dose-dependent manner in patients with newly-diagnosed diabetes mellitus.

Increased Risk of Bullous Pemphigoid after First-Ever Stroke: A Population-Based Study.

BACKGROUND: We hypothesize that autoantibodies are induced after the blood-brain barrier is damaged by stroke and the risk of bullous pemphigoid (BP) is increased after stroke. We assess the risk of BP after first-ever stroke in a nationwide population-based cohort of first-ever stroke patients. METHODS: We extracted data from the Longitudinal Health Insurance Database 2005 and identified patients with first-ever stroke as well as control patients matched for age, gender, and year of enrollment. The risk of BP in first-ever stroke patients in comparison with that in control patients was analyzed using Cox regression. RESULTS: Of 12,607 patients with first-ever stroke, 38 (0.3%) patients developed BP in a median of 3.5 years. In the control patients, 8 persons (0.06%) had BP in a median of 3.7 years. The crude hazard ratio (HR) of BP in first-ever stroke patients was 4.83 (95% CI 2.25-10.34, p < 0.001) compared to the control group. The adjusted HR was 4.20 (95% CI 1.94-9.08, p < 0.001) after adjustments for age, gender, hypertension, diabetes, dementia, epilepsy, Parkinson disease, furosemide, and neuroleptics for stroke patients. CONCLUSIONS: The risk of BP is increased in first-ever stroke patients in a nationwide population-based cohort and this association is independent of well-known confounders of BP.

Risk of parkinsonism induced by flunarizine or cinnarizine: a population-based study.

PURPOSE: This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls. METHODS: Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997-1999, a history of neurodegenerative diseases, and an age of less than 30 years. One matched control for each patient was selected. Each participant was followed for diagnosis of parkinsonism within a 3-year observation period. Stroke, diabetes mellitus, total prescription days, and doses of flunarizine or cinnarizine were recorded. RESULTS: The study and control groups consisted of 9830 subjects. In the study group, 280 patients (2.9 %) were diagnosed with parkinsonism with a median observation period of 1.2 years, and 49 participants (0.5 %) were diagnosed in the control group with a median observation period of 1.9 years. The adjusted hazard ratio for parkinsonism among patients receiving flunarizine and cinnarizine was 5.117 (95 % CI = 3.758-6.967). Age, stroke, and diabetes mellitus were significant risk factors, but female sex and total doses of the study drugs were not. CONCLUSIONS: This study demonstrates that flunarizine and cinnarizine significantly increase the risk for parkinsonism. The treatment benefits of these two agents should be balanced with this adverse effect. Physicians must look carefully for early signs of parkinsonism in patients treated with flunarizine and cinnarizine.

Inverse Association Between Cancer and Dementia: A Population-based Registry Study in Taiwan.

Dementia and cancer are 2 common diseases in the elderly. This retrospective cohort study used a population-based insurance claim dataset, merged with a cancer registry, to test whether risk reduction of cancers occurs at various primary sites after diagnosis of dementia. The study included a cohort of 3282 patients who were first diagnosed with dementia between 2001 and 2002. A control cohort consisted of 13,128 subjects matched for age, sex, and year of enrollment. The site of cancer and duration between the diagnosis of dementia and cancer were analyzed. Among the dementia cases, 169 patients (5.2%) were diagnosed with cancer during a median observation period of 40 months. In the control group, 976 subjects (7.4%) were diagnosed with cancer, during a median observation period of 46 months. During a 7-year follow-up period, the adjusted hazard ratio for cancer among dementia patients was 0.77 (95% confidence interval, 0.65-0.91), and significantly lower for colon (0.54, 0.29-0.99) and prostate cancers (0.44, 0.20-0.98). This study showed an inverse association between cancer and dementia. Further studies focusing on colon and prostate cancers may help elucidate the underlying mechanism and expand the therapeutic strategies.

Topiramate may not increase risk of urolithiasis: A nationwide population-based cohort study.

PURPOSE: Topiramate is an effective anti-epileptic drug and can be associated with increased risk for urolithiasis because of its effects on acid-base profile. Evidences that supported an association of topiramate and urolithiasis were limited to case reports or series. We investigated the association of topiramate and urolithiasis in a nationwide population-based cohort study. METHODS: We analyzed 1377 patients receiving topiramate and 1377 age- and gender-matched control patients (not receiving topiramate) between 1997 and 2008. The risk of urolithiasis was analyzed using Kaplan-Meier analysis, followed by Cox proportional hazard regression. RESULTS: Of the 2754 patients, 79 (2.9%) patients developed urolithiasis in two (interquartile range: 1.2-4.2) years. The proportion of patients who developed urolithiasis in the patients receiving topiramate was not different from that of the control patients (p=0.138, χ(2) test). The urolithiasis free survival was not different between the patients receiving topiramate and the control patients (p=0.168) in Cox proportional hazard regression. The duration and total dosage of topiramate were not associated with risk of urolithiasis in patients receiving topiramate (p=0.482 and p=0.751). CONCLUSION: Topiramate may not increase the risk of urolithiasis. The duration and the total dosage of topiramate were not associated with urolithiasis risks.

Clinical efficacy and cognitive and neuropsychological effects of levetiracetam in epilepsy: an open-label multicenter study.

The aim of this prospective, multicenter, open-label study was to investigate the efficacy of levetiracetam (LEV) and determine its effects on cognitive and neuropsychological function. Sixty-nine patients were evaluated for effects of LEV on seizure control, cognitive (Mini-Mental State Examination [MMSE]) and neuropsychological (Symptom Checklist-90 Revised [SCL-90-R]) functions, and quality of life (Quality of Life in Epilepsy--10 [QOLIE-10]) assessments at 3 and 12 months of follow-up. Thirty-nine percent of patients achieved seizure freedom, and 68% had a > or =50% seizure frequency reduction after 1 year of LEV (1235.5+/-392.7 mg/day). There were also significant improvements in mean MMSE score and in the recall and language items of MMSE. There were modest improvements in interpersonal sensitivity and paranoid ideation scales of the SCL-90-R, and improvements in cognition and medication effect items of the QOLIE-10. The results demonstrate that LEV not only effectively reduces seizure frequency, but also possibly contributes to improvements in neuropsychological functions such as recall, language, interpersonal sensitivity, and paranoid ideation.

Elevation of serum aminotransferase activity increases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

BACKGROUND AND AIM: Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of atherosclerosis and alanine aminotransferase (ALT) is associated with insulin resistance independently of metabolic factors. The aim of the present study was to investigate whether NAFLD patients with ALT elevation had a higher risk of carotid atherosclerosis. METHODS: A total of 190 individuals were enrolled from the health management center. Among them, 20 subjects were excluded due to the presence of hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (HCV) and cardiovascular disease. NAFLD was diagnosed by ultrasound examination. Carotid ultrasonography was used to measure maximal intima-media thickness (IMT) of the common carotid artery (CCA) and IMT (mean) > 1.0 mm was defined as the presence of carotid atherosclerosis. RESULTS: NAFLD patients with ALT elevation had increased risk of carotid atherosclerosis than those with normal ALT by Fisher's exact test (P < 0.05). Multivariate analyses showed that serum ALT levels were positively associated with carotid atherosclerosis after adjustment for age, sex, number of metabolic syndrome components or status of metabolic syndrome (OR, 1.44; 95% CI 1.09-1.89; OR, 1.45; 95% CI 1.11-1.91). In addition, the higher the serum ALT levels with every 10 IU/L increment, the greater the risk of carotid atherosclerosis. CONCLUSIONS: Serum ALT levels are positively associated with the risk of carotid atherosclerosis in patients with NAFLD, suggesting that serum ALT levels could serve as a surrogate marker of cardiovascular risk in this special clinical setting.