Association between Antihyperlipidemic Agent Use and Age-Related Macular Degeneration in Patients with Hyperlipidemia: A Population-Based Retrospective Cohort Study.

Several studies have indicated that lipoproteins might contribute to the pathogenesis of age-related macular degeneration (AMD). In this population-based retrospective cohort study, patients with hyperlipidemia were divided into two groups (study groups I and II) based on whether or not they were receiving antihyperlipidemic agents. The comparison group included patients without hyperlipidemia who were randomly selected and matched with study group II patients. A Cox proportional hazard model was used to evaluate the risk of AMD among the groups. Patients with hyperlipidemia receiving antihyperlipidemic agents (study group I, n = 15,482) had a significantly increased AMD risk (adjusted hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 1.04-1.45) compared to those not receiving antihyperlipidemic agents (study group II, n = 15,482). However, with an increase in cumulative exposure, a reduced risk of AMD was observed in patients using a defined daily dose of more than 721, with an adjusted HR of 0.34 (95% CI = 0.22-0.53, p < 0.001). Additionally, the adjusted HR of AMD for study group II was 1.40 (95% CI = 1.20-1.63, p < 0.001) relative to the comparison group (n = 61,928). In conclusion, the study results indicated that patients with hyperlipidemia have a higher AMD risk than patients without hyperlipidemia. Furthermore, patients with hyperlipidemia who received antihyperlipidemic agents had a significantly increased AMD risk. However, a dose-dependent reduction in the risk of AMD was observed in patients with hyperlipidemia using statins or/and fibrates.

Association between statin use and the risk of gout in patients with hyperlipidemia: A population-based cohort study.

Objective: To investigate the association between statin use and risk of gout in patients with hyperlipidemia. Methods: In this population-based retrospective cohort study, patients ≥20 years and diagnosed as having incident hyperlipidemia between 2001 and 2012 were identified from the 2000 Longitudinal Generation Tracking Database in Taiwan. Regular statin users (incident statin use, having 2 times and ≥90 days of prescription for the first year) and two active comparators [irregular statin use and other lipid-lowering agent (OLLA) use] were compared; the patients were followed up until the end of 2017. Propensity score matching was applied to balance potential confounders. Time-to-event outcomes of gout and dose- and duration-related associations were estimated using marginal Cox proportional hazard models. Results: Regular statin use non-significantly reduced gout risk compared with irregular statin use (aHR, 0.95; 95% CI, 0.90-1.01) and OLLA use (aHR, 0.94; 95% CI, 0.84-1.04). However, a protective effect was noted for a cumulative defined daily dose (cDDD) of >720 (aHR, 0.57; 95% CI, 0.47-0.69 compared with irregular statin use and aHR, 0.48; 95% CI, 0.34-0.67 compared with OLLA use) or a therapy duration of >3 years (aHR, 0.76; 95% CI, 0.64-0.90 compared with irregular statin use and aHR, 0.50; 95% CI, 0.37-0.68 compared with OLLA use). Dose- and duration-dependent associations were consistent in the 5-year sensitivity analyses. Conclusion: Although statin use was not associated with a reduction in gout risk, the protective benefit was observed in those receiving higher cumulative doses or with a longer therapy duration.

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.

The effects of medications for treating COPD and allied conditions on stroke: a population-based cohort study.

Patients with chronic obstructive pulmonary disease (COPD) are at higher risk of stroke. This study aimed to investigate the clinical factors of stroke risk in COPD and allied conditions patients and associations between medications for treating COPD and allied conditions. The population-based study cohort comprised 24,173 patients diagnosed with COPD and allied conditions between 2000 and 2013, and 24,170 selected matched patients without COPD comprised the comparison cohort from a nationwide database. Cox-proportional hazard regression was performed to determine the impact of medical therapies, comorbidities, and other clinical factors on stroke risk. Of the 48,343 included patients, 1394 (2.9%) experienced stroke during follow-up, with a significant difference between COPD and allied conditions cohort (1003/4.2%) and comparison cohort (391/1.6%) (adjusted hazard ratio [aHR]: 2.72, p < 0.001). Cox-regression analysis revealed that COPD and allied conditions patients who were older (>65 years) (HR: 1.06); male (HR: 1.39); with hypertension (HR: 1.46), diabetes mellitus (HR: 1.33) and atrial fibrillation (HR: 1.63) had increased stroke risk. Mucolytics (HR: 0.44) and combination therapy with inhaled corticosteroids (ICS) and long-acting ß2-agonists (LABA) (HR: 0.75) were associated with decreased stroke risk in COPD and allied conditions patients. Among COPD and allied conditions patients, major comorbidities increase risk of stroke. Therapy with mucolytic agents and combination ICS/LABA is associated with risk reduction.

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.

Use of gastric acid-suppressive agents increases the risk of dementia in patients with upper gastrointestinal disease: A population-based retrospective cohort study.

BACKGROUND: Prescriptions for gastric acid-suppressive agents, including proton-pump inhibitors (PPIs) and histamine type-2 receptor antagonists (H2RAs), are rising. However, little data exist regarding their association with dementia in the Asian population. The objective of this study was thus to investigate the impact of the use of PPIs and H2RAs on the risk of dementia in an Asian population with upper gastrointestinal disease (UGID). METHODS: We conducted a population-based retrospective cohort study with a 10-year follow-up using data from 2000 to 2015 derived from Taiwan's Longitudinal Health Insurance Database. We included 6711 patients with UGID receiving gastric acid-suppressive agents, 6711 patients with UGID not receiving agents, and 6711 patients without UGID or treatment thereof, all at least 20 years of age. Groups were matched for age, sex, and index date. The association between gastric acid-suppressive agent use and dementia was analyzed using a Cox proportional hazards regression model adjusted for potential confounders. RESULTS: The adjusted hazard ratio (aHR) of dementia for patients with UGID receiving gastric acid-suppressive agents compared with patients with UGID without gastric acid-suppressive agents was 1.470 (95% confidence interval [CI] 1.267-1.705, p < 0.001). Both PPIs and H2RAs increase the risk of dementia (PPIs: aHR 1.886 [95% CI 1.377-2.582], p < 0.001; H2RAs: aHR 1.357 [95% CI 1.098-1.678], p < 0.01), with PPIs exhibiting significantly greater risk (aHR 1.456 [95% CI 1.022-2.075], p < 0.05). CONCLUSIONS: Our results demonstrate an increased risk of dementia in patients with UGID receiving gastric acid-suppressive agents, including PPIs and H2RAs, and the use of PPIs was associated with a significantly greater risk than H2RA use.

Association between acid-suppressive drug use and atopic dermatitis in patients with upper gastrointestinal diseases: A population-based retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: Proton-pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are two of the most widely used acid-suppressive drugs (ASDs). Some studies have reported that prenatal ASD exposure may increase the risk of asthma and other allergic diseases. This study investigated the effects of ASDs on the risk of atopic dermatitis in patients with upper gastrointestinal diseases. METHODS: This population-based retrospective cohort study used data of 289,850 patients with at least two diagnoses of upper gastrointestinal diseases (UGIDs) between 1 January 2001 and 31 December 2005, from Taiwan's National Health Insurance Research Database. The AD risks among ASD users and nonusers were compared. Differences in sociodemographic characteristics and potential covariates were examined. AD hazard ratios were estimated, and groups were compared using Cox proportional hazards regression analysis after adjustment for age, sex and other covariates. RESULTS AND DISCUSSION: In total, 109,980 patients were included. The adjusted hazard ratio (HR) of AD risk in ASD users relative to that in nonusers was 1.52 (95% confidence interval [CI]: 1.40-1.64, p < 0.001). For a dose-effect sub-analysis, patients were divided into four groups based on their defined daily dose. ASDs dose-dependently affected the AD risk (p for trend <0.01). Furthermore, the adjusted HR of the AD risk among ASD nonusers was 2.30 (95% CI: 2.06-2.57) relative to that in the comparison group (ASD nonusers without UGIDs). Among patients with UGIDs, ASD users had a higher AD risk than ASD nonusers. A subgroup analysis revealed only H2RA use was associated with an increased AD risk (adjusted HR 1.70, 95% CI: 1.53-1.89, p < 0.001). WHAT IS NEW AND CONCLUSIONS: These results indicate that the use of H2RAs was associated with an increased risk of AD among patients with UGIDs, and the increase in risk appeared to be dose-dependent. ASDs should be used only in situations where clear clinical benefits can be obtained.

Association Between Use of Antihyperlipidemic Agents and Chronic Obstructive Pulmonary Disease in Patients with Hyperlipidemia: A Population-Based Retrospective Cohort Study.

Objective: The effect of statins and fibrates on the risk of chronic obstructive pulmonary disease (COPD) remains unclear. The aim of this study was to investigate the effects of statins and fibrates on the risk of COPD in patients with hyperlipidemia. Patients and Methods: This study involved a retrospective cohort with a follow-up period of 6 years. We identified patients who were diagnosed as having hyperlipidemia between 2000 and 2016 from Taiwan's National Health Insurance Research Database. A Cox proportional hazard model was used to estimate the risk of COPD among different groups. The dose-related effects of statins and fibrates on the risk of COPD were evaluated according to the defined daily dose (DDD). Results: Patients with hyperlipidemia not using statins and fibrates (group II) had a significantly higher risk of COPD compared with their comparison group, with an adjusted hazard ratio (HR) of 1.091 [95% confidence interval (CI): 1.034-1.152, p < 0.01]. Dose-dependent reduction in the risk of COPD was observed in patients with hyperlipidemia using statins or fibrates compared with patients not using them. Moreover, with an increase in cumulative exposure, a reduced risk of COPD was observed in patients using more than 361 DDDs, with an adjusted HR of 0.474 (95% CI: 0.401-0.559, p < 0.001). Patients on fibrate monotherapy using more than 541 DDDs were observed to have an adjusted HR of 0.454 (95% CI: 0.226-0.910, p < 0.05) and those on statin monotherapy with over 361 DDDs were noted to have an adjusted HR of 0.583 (95% CI: 0.459-0.740, p < 0.001). Conclusion: This study demonstrated that an increase in the cumulative exposure of statins and fibrates significantly reduced the risk of COPD in patients with hyperlipidemia, and the risk reduction appeared to be significantly dose dependent.

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.

The use of proton pump inhibitors decreases the risk of diabetes mellitus in patients with upper gastrointestinal disease: A population-based retrospective cohort study.

OBJECTIVES: The aim of this study was to investigate the effects of proton pump inhibitors (PPIs) on the risk of diabetes mellitus (DM) among patients with upper gastrointestinal disease (UGID). METHODS: This was a retrospective cohort study with a follow-up period of 5 years. We identified 388,098 patients who were diagnosed with UGID between 2000 and 2006 from the Longitudinal Health Insurance Database of the Taiwan National Health Insurance program. We used Cox proportional hazard ratio (HR) to compare the risk of DM between UGID patients received PPIs and those did not receive PPIs. HRs were adjusted for possible confounders, including age, sex, hypertension, gout and/or hyperuricemia, coronary artery disease, stroke, pancreatitis, hyperlipidemia, obesity, H2-blocker use, and clozapine or olanzapine use. The dose-related effects of PPIs on the risk of DM were evaluated according to the defined daily dose (DDD). RESULTS: The adjusted HR was 0.80 (95% CI, 0.73-0.88) for the study group (UGID patients with PPIs) compared with comparison group I (UGID patients without PPIs). Among patients who used PPIs, those older than 60 years of age had a lower risk of DM (HR, 0.73; 95% CI, 0.63-0.83) than those younger than 40 years. Additionally, the effect of PPIs was significantly dose-dependent (P for trend <0.001). Patients with UGID who received >540 DDDs of PPIs exhibited the greatest reduction in the risk of DM. CONCLUSIONS: Our results demonstrated a decreased risk of DM in UGID patients who used PPIs; the risk appeared to be significantly dose-dependent.

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.

Atrial Fibrillation and Coronary Artery Disease as Risk Factors of Retinal Artery Occlusion: A Nationwide Population-Based Study.

We use Taiwanese national health insurance research database (NHIRD) to investigate whether thrombolism (carotid artery disease (CAD) as a surrogate) or embolism (atrial fibrillation (AF) as a surrogate) plays roles in later retinal artery occlusion (RAO) development and examine their relative weights. The relative risks of RAO between AF and CAD patients and controls were compared by estimating the crude hazard ratio with logistic regression. Kaplan-Meier analysis was used to calculate the cumulative incidence rates of developing RAO, and a log-rank test was used to analyze the differences between the survival curves. Separate Cox proportional hazard regressions were done to compute the RAO-free rate after adjusting for possible confounding factors such as age and sex. The crude hazard ratios were 7.98 for the AF group and 5.27 for the CAD group, and the adjusted hazard ratios were 8.32 and 5.34 for the AF and CAD groups, respectively. The observation time with RAO-free was shorter for AF compared with CAD group (1490 versus 1819 days). AF and CAD were both risk factors for RAO with different hazard ratios. To tackle both AF and CAD is crucial for curbing RAO.

Increased Risk of Acute Pancreatitis in Patients with Rheumatoid Arthritis: A Population-Based Cohort Study.

The study was conducted to determine whether patients with rheumatoid arthritis (RA) are at increased risk of acute pancreatitis compared with those without RA and to determine if the risk of acute pancreatitis varied by anti-RA drug use. We used the large population-based dataset from the National Health Insurance (NHI) program in Taiwan to conduct a retrospective cohort study. Patients newly diagnosed with RA between 2000 and 2011 were referred to as the RA group. The comparator non-RA group was matched with propensity score, using age and sex, in the same time period. We presented the incidence density by 100,000 person-years. The propensity score and all variables were analyzed in fully adjusted Cox proportional hazard regression. The cumulative incidence of acute pancreatitis was assessed by Kaplan-Meier analysis, with significance based on the log-rank test. From claims data of one million enrollees randomly sampled from the Taiwan NHI database, 29,755 adults with RA were identified and 119,020 non-RA persons were matched as a comparison group. The RA cohort had higher incidence density of acute pancreatitis (185.7 versus 119.0 per 100,000 person-years) than the non-RA cohort. The adjusted hazard ratio (HR) was 1.62 (95% CI [confidence interval] 1.43-1.83) for patients with RA to develop acute pancreatitis. Oral corticosteroid use decreased the risk of acute pancreatitis (adjusted HR 0.83, 95% CI 0.73-0.94) but without a dose-dependent effect. Current use of disease modifying anti-rheumatic drugs or tumor necrosis factor blockers did not decrease the risk of acute pancreatitis. In conclusion, patients with RA are at an elevated risk of acute pancreatitis. Use of oral corticosteroids may reduce the risk of acute pancreatitis.

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.

Risk of cancer among HIV-infected patients from a population-based nested case-control study: implications for cancer prevention.

BACKGROUND: The burden of cancer is likely to increase among the human immunodeficiency virus (HIV)-positive population as it ages due to successful antiretroviral therapy (ART). The purpose of this study was to determine the risk of cancer in HIV-infected patients. METHODS: This study was a matched nested case-control study. It was performed using the National Health Insurance Research Database of Taiwan. The control group included non-HIV-infected patients matched by sex, age, and year of enrollment. Logistic regression analyses were performed and simultaneously adjusted for potential confounders (income, urbanization, and Charslon index of comorbidity to evaluate HIV infection as an independent risk of cancer. We calculated the overall and sex-specific standardized incidence ratios (SIR) to investigate the pattern of cancer risk and overall cancer risk in the patients with HIV infection. RESULTS: Of the 1,115 HIV-infected patients, 104 (9.33%) developed cancer during the 11-year follow-up period. The risk of cancer for patients with HIV infection was significant (adjusted odds ratio = 3.89, 95% confidence interval [CI] = 2.92-5.19) after adjustment for potential confounders. There was a significantly increased risk of developing non-Hodgkin lymphoma (SIR = 25.73, 95% CI = 6.83-90.85), cervical cancer (SIR = 4.01, 95% CI = 1.0-16.06), lymphoma (SIR = 20.26, 95% CI = 5.86-70.10), and respiratory and intrathoracic cancer (SIR = 20.09, 95% CI = 2.34-172.09) compared with the control group. In addition, HIV-infected patients were at significant risk for renal, oral, breast, liver, skin, and colorectal cancer. CONCLUSIONS: Patients with HIV infection are at increased risk for several specific cancers. Our results support the implementation of an active and accelerated cancer screening schedule for patients with HIV infection to increase their life span.

Proton pump inhibitor usage and the associated risk of pneumonia in patients with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a serious medical problem and public health issue in Taiwan. Gastrointestinal symptoms frequently occur in patients with CKD, and proton pump inhibitors (PPIs) have therapeutic indications for gastrointestinal disorders involving excessive acid production. However, PPIs may also increase the risk of developing pneumonia through acute and irreversible gastric acid suppression. This study aimed to characterize differences in the risk of pneumonia in patients with CKD who use PPIs. METHODS: This population-based case-control cohort study in Taiwan collected data from the Taiwan Health Insurance Research Database. Cases studied consisted of all patients in the database with an initial diagnosis of CKD during the 5-year period from 1997 to 2002. Each patient with CKD who used PPIs during this 5-year period was tracked to identify the occurrence of any type of pneumonia. We estimated the adjusted hazard ratios (HRs) and 95% confidence interval (95% CI) by using multiple logistic regression analysis. RESULTS: The adjusted HR of the risk of pneumonia for patients with CKD using PPIs was 2.21 (95% CI = 1.59-3.07, p < 0.001). The risk of pneumonia was found to be positively associated with administration of PPIs. We observed a greater risk of pneumonia in patients with CKD using PPIs than in patients not using PPIs. CONCLUSION: Results of this study suggest that use of PPIs in CKD patients may be associated with increasing the risk of pneumonia. Physicians should exercise caution while prescribing PPIs for patients with CKD.

Outcome of nonadherence to antimicrobial treatment guidelines in ambulatory patients with acute cystitis: a nationwide population-based study.

OBJECTIVE: The recurrence rate after acute cystitis treatment failure with inappropriate antimicrobials remains unclear. The goal of this study was to explore the relationship between cystitis recurrence and nonadherence of antimicrobial prescriptions to national guidelines using a nationwide population-based data set. METHODS: This was a retrospective longitudinal observational cohort study that was conducted using the clinical records of the National Health Insurance Research Database in Taiwan from 2006-2007. After excluding patients younger than 18 years of age, with concurrent infections, urinary tract anomaly, and no antimicrobial treatment, the remaining study population included 36,395 patients with acute cystitis. We evaluated the hazard ratio (HR) of cystitis recurrence within 28 days between the adherence and nonadherence groups using Cox proportional hazard regression analysis. RESULTS: Adherence to antimicrobial prescription guidelines was the factor that most strongly influenced acute cystitis recurrence, with a HR of 0.91 (95% confidence interval 0.87-0.95) after adjusting for all variables. The incidence rate of acute cystitis in patients receiving antimicrobials adherent to national guidelines was 59.78 per 10,000 person-days. The results of the likelihood ratio test indicated that age, sex, and guideline nonadherence were significant risk factors for recurrent cystitis. The percentage of first-generation cephalosporin prescription was 31.61%, making it the most frequently prescribed guideline-recommended drug. CONCLUSION: Acute cystitis patients with or without multiple chronic comorbidities should be treated with antimicrobials that adhere to recommended guidelines to attain a better therapeutic outcome.