Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population-based cohort study.

AIM: Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We aimed to examine the association between thiazolidinediones, PPAR-γ agonists and incidence of bacterial abscess among patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study between 2000 and 2010 included 46 986 propensity (PS)-matched patients diagnosed with type 2 diabetes. We compared the incidence of bacterial abscess, including liver and non-liver abscesses, between patients treated with metformin plus a thiazolidinedione (M + T, N = 7831) or metformin plus a sulfonylurea (M + S, N = 39 155). Data were retrieved from a population-based Taiwanese database. We applied Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), comparing M + T and M + S after PS matching. RESULTS: During a median follow-up of 4.5 years, the incidence rate of bacterial abscess was lower with M + T than with M + S treatment (1.89 vs 3.15 per 1000 person-years) in the PS-matched cohort. M + T was associated with a reduced risk of bacterial abscess (HRs after PS matching, 0.58; 95% CI, 0.42-0.80 for total bacterial abscess; 0.54; 95% CI, 0.28-1.07 for liver abscess; 0.59; 95% CI, 0.41-0.85 for non-liver abscess). Results did not change materially after accounting for unmeasured confounding factors using high-dimenional PS matching and differential censoring between regimen groups. Rosiglitazone and pioglitazone, in combination with metformin, produced similar reductions in risk of all abscess outcomes. CONCLUSION: We found that M + T may provide a protective benefit in reducing the incidence of bacterial abscesses. These findings merit further investigation.

Dipeptidyl Peptidase-4 Inhibitor Use Is Not Associated With Acute Pancreatitis in High-Risk Type 2 Diabetic Patients: A Nationwide Cohort Study.

To analyze the association between use of DPP-4 inhibitors and acute pancreatitis in high-risk type 2 diabetic patients. A retrospective nationwide cohort study was conducted using the Taiwan National Health Insurance claim database. The risk associated with sitagliptin was compared to that with acarbose, a second-line antidiabetic drug prescribed for patients with similar diabetes severity and with a known neutral effect on pancreatitis. Between January 1, 2009 and December 31, 2010, a total of 8526 sitagliptin initiators and 8055 acarbose initiators who had hypertriglyceridemia or prior hospitalization history for acute pancreatitis were analyzed for the risk of hospitalization due to acute pancreatitis stratified for baseline propensity score. In the crude analysis, sitagliptin was associated with a decreased risk of acute pancreatitis (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.62-0.88) compared to acarbose in diabetic patients with prior history of hospitalization for pancreatitis or hypertriglyceridemia. The association was abolished after stratification for propensity score quintiles (adjusted HR 0.95; 95% CI: 0.79-1.16). Similar results were found separately in both patients' histories of prior hospitalization of acute pancreatitis (adjusted HR 0.97; 95% CI: 0.76-1.24) and those with hypertriglyceridemia (adjusted HR 0.86; 95% CI: 0.65-1.13). No significant association was found for different durations or accumulative doses of sitagliptin. In the stratified analysis, no significant effect modification was found in relation to patients' characteristics. Use of sitagliptin was not associated with an increased risk of acute pancreatitis in high-risk diabetic patients with hypertriglyceridemia or with history of acute pancreatitis.

Comparative Cardiovascular and Cerebrovascular Safety of Inhaled Long-Acting Bronchodilators in Patients with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

STUDY OBJECTIVE: Inhaled long-acting bronchodilators are commonly used as maintenance therapy in chronic obstructive pulmonary disease (COPD). We compared the risk of cardiovascular and cerebrovascular events among patients with COPD treated with inhaled long-acting bronchodilator monotherapy and combination therapy. DESIGN: Retrospective cohort study. SETTINGS: A population-based health care database from Taiwan. PATIENTS: Individuals with COPD who initiated long-acting muscarinic antagonists (LAMAs) alone, long-acting ß-2 agonists (LABA) alone, and LABA and LAMA in combination between 2001 and 2010. MEASUREMENTS AND MAIN RESULTS: We used Cox regression models to compare a composite cardiovascular outcome, defined as hospitalization for acute myocardial infarction, congestive heart failure, and cerebrovascular diseases among the three treatment groups, adjusting for potential confounders. Among a cohort of 3458 study-eligible patients, we identified 505 composite cardiovascular events during 10,590 patient-years of follow-up. In the primary analysis which considered first exposure carried forward, LABA alone and LAMA alone were associated with similar risks of the composite outcome (hazard ratio [HR] 1.09; 95% confidence interval [CI] 0.87-1.37). The HR comparing LABA and LAMA in combination with LAMA alone was 1.13 (95% CI 0.60-2.13) and to LABA alone was 1.03 (95% CI 0.55-1.92). The secondary analysis in which we allowed patients to reenter the cohort upon treatment change yielded similar results, but with slightly higher HRs comparing LABA and LAMA in combination with LAMA alone (HR 1.26, 95% CI 0.74-2.15) and to LABA alone (HR 1.31, 95% CI 0.80-2.13). CONCLUSIONS: Our results suggest similar cardiovascular and cerebrovascular safety of LABA and LAMA when agents are used alone. Additional studies are needed to rule out potential risk associated with inhaled long-acting bronchodilator combination therapy.

Time trends in the prevalence and incidence of Parkinson's disease in Taiwan: A nationwide, population-based study.

BACKGROUND/PURPOSE: Identifying trends in the prevalence and incidence of Parkinson's disease (PD) may yield information that supports public health goals. Our aim was to evaluate time-trend changes in the prevalence and incidence of PD in Taiwan between 2004 and 2011. METHODS: This retrospective, nationwide, longitudinal study used the Taiwan National Health Insurance Research Database to identify patients with PD from 2004 to 2011 based on having ICD-9-CM diagnostic codes, which were assigned by neurologists, and being prescribed PD medication. Annual incidence and prevalence were calculated, and time-trend analyses were estimated assuming a Poisson distribution. RESULTS: Over the study period, 19,302 patients in 2004 and 41,606 patients in 2011 fulfilling the study criteria for PD were included in the analysis. The average age-standardized prevalence of PD per 100,000 of population was 84.8 in 2004 and 147.7 in 2011, with a 7.9% yearly increase. Increasing prevalence trends of PD were statistically significant (p < 0.001) in all age groups, with the steepest rate among those aged ≥ 80 years. In contrast, the average age-standardized incidence of PD decreased steadily from 35.3 per 100,000 in 2005 to 28.8 per 100,000 in 2011. The incidence rate was higher in men than in women, and increased with age. CONCLUSION: We identified an increasing trend in the annual prevalence rates of PD from 2004 to 2011; however, the substantial decline in the incidence of PD suggests that some major environmental risk factors for PD were removed from this population during this time period.

Cardiovascular risk associated with acarbose versus metformin as the first-line treatment in patients with type 2 diabetes: a nationwide cohort study.

CONTEXT: Metformin is the first-line oral therapy for type 2 diabetes with proven benefits against cardiovascular risk. Recent evidence suggested that acarbose might be similar to metformin in glucose-lowering efficacy and cardiovascular risk reduction. Therefore, international guidelines have suggested the use of acarbose as alternative first-line antidiabetic therapy. OBJECTIVE: To compare the cardiovascular outcomes in the first-line users of acarbose vs metformin. DESIGN, SETTING, PATIENTS, AND OUTCOME MEASURES: A nationwide cohort study was conducted by analyzing the Taiwan National Health Insurance (NHI) Database. A total of 17,366 acarbose initiators and 230,023 metformin initiators were identified between January 1, 2009 and December 31, 2010. The primary outcome is hospitalization due to any cardiovascular events, including acute myocardial infarction, congestive heart failure, and ischemic stroke. The propensity score method was used to adjust for baseline differences between the two groups. Patients were followed from drug initiation to the earliest of outcome occurrence, death or disenrollment from NHI, or study termination. RESULTS: In intention-to-treat analyses, acarbose was associated with a higher risk of any cardiovascular event (adjusted hazard ratio [HR]: 1.05; 95% confidence interval [CI], 1.01-1.09), heart failure (HR, 1.08; 95% CI, 1.00-1.16), and ischemic stroke (HR, 1.05, 95% CI, 1.00-1.10) than metformin. No significant difference in risk was found in subgroups of patients with or without underlying hypertension, ischemic heart disease, or cerebrovascular disease. Similar results were found in auxiliary as-treated analyses or analyses stratified by propensity score quintiles. CONCLUSION: Our data do not support that acarbose has a cardio-protective effect similar to metformin as a first-line antidiabetic agent.

Severe hepatic injury associated with different statins in patients with chronic liver disease: a nationwide population-based cohort study.

BACKGROUND AND AIM: The hepatotoxicity of statins in patients with chronic liver diseases remains unclear. In this study, we aimed to estimate the risk of severe hepatic injury associated with different statins in patients with chronic liver disease. METHODS: A nationwide population-based cohort study was conducted by analyzing the Taiwan National Health Insurance database. A total of 37,929 subjects with chronic liver disease who started statin therapy were identified during the period of January 1, 2005 to December 31, 2009. Outcome was defined as hospitalization due to liver injury. RESULTS: During a total of 118,772 person-years of follow-up, 912 incident cases of hospitalization due to hepatic injury are identified. The incidence rate was 2.95, 2.49, 2.92, 1.94, 2.65, and 2.52 per 100,000 person-days for atorvastatin, lovastatin, fluvastatin, pravastatin, simvastatin, and rosuvastatin initiators, respectively. Overall, there was no difference in the incidence associated with different statins. However, when each statin was further categorized to high (≧ 0.5 defined daily dose) or low (< 0.5 defined daily dose) mean daily dose, only high-dose atorvastatin was significantly associated with increased risk of hospitalization due to hepatic injury (hazard ratio, 1.62; 95% confidence interval, 1.29, 2.03) as compared with low-dose atorvastatin. CONCLUSION: The overall incidence of hospitalization due to severe hepatic injury was low among statin initiators with chronic liver disease. Only high-dose atorvastatin was associated with increased risk.

Effectiveness and safety of extracranial carotid stent placement: a nationwide self-controlled case-series study.

BACKGROUND: Carotid angioplasty and stent (CAS) placement has emerged as an attractive revascularization strategy for patients with internal carotid artery stenosis. However, the effectiveness and safety of CAS were not fully evaluated, mainly because of methodological difficulties in finding an appropriate comparison group. METHODS: Patients who underwent CAS were identified from Taiwan's National Health Insurance claims database between 2005 and 2008. The incidence rate of ischemic stroke after CAS was compared with that of the year prior to the procedure using a self-controlled case series analysis and a conditional Poisson regression model. Logistic regression was conducted to identify factors associated with poor outcome. RESULTS: A total of 1258 patients who had undergone CAS were included, and 73 cases (5.8%) of death or ischemic stroke occurred during the index hospitalization. Within 1 year after CAS, 74 patients died and 80 experienced an ischemic stroke. Of the 1184 patients who were followed for 360 days, the rate ratio for ischemic stroke decreased to 0.21 (95% CI: 0.08-0.51) between 31 and 180 days, and 0.10 (95% CI: 0.03-0.32) between 181 and 360 days. Statin therapy was associated with a reduced risk of death or ischemic stroke in the 1(st) month (odds ratio of 0.53; 95% CI: 0.32-0.90). Conversely, the use of nonsteroidal anti-inflammatory agents, possibly histamine-2 receptor blockers, and CAS performed by low-volume operators were associated with a twofold increased risk. CONCLUSION: CAS reduced the long-term risk for ischemic stroke. Self-controlled case series analysis might be an appropriate design for evaluating device safety and effectiveness.

Risk of Parkinson's disease following severe constipation: a nationwide population-based cohort study.

INTRODUCTION: Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample. METHODS: 551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models. RESULTS: After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14-5.03), 3.83 (2.51-5.84), and 4.22 (2.95-6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43-3.33), 5.22 (4.61-5.92), and 10.47 (9.46-11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant. CONCLUSIONS: Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner.

Oseltamivir use and outcomes during the 2009 influenza A H1N1 pandemic in Taiwan.

BACKGROUND: The Taiwan CDC provided free oseltamivir to all patients with influenza infections confirmed by rapid testing or who had clinical warning symptoms during the 2009 H1N1 influenza pandemic in Taiwan. However, oseltamivir utilization patterns, cost, and outcomes among oseltamivir-treated patients remained unclear. METHOD: A population-level, observational cohort study was conducted using the Taiwan National Health Insurance Database from January to December 2009 to describe the use of oseltamivir. RESULT: Prescription trend over weeks increased after a change in government policy and responded to the influenza virus activity. The overall prescription rate was 22.33 per 1000 persons, with the highest prescription rate of 116.5 for those aged 7-12 years, followed by 69.0 for those aged 13-18 years, while the lowest rate was 1.7 for those aged ≥ 65 years. As influenza virus activity increased, the number of prescriptions for those aged ≤18 years rose significantly, whereas no substantial change was observed for those aged ≥65 years. There were also regional variations in terms of oseltamivir utilization and influenza complication rates. CONCLUSIONS: Oseltamivir was widely used in the 2009 H1N1 influenza pandemic in Taiwan, particularly in those aged 7-18 years. The number of prescriptions for oseltamivir increased with a change in government policy and with increasing cases of pandemic influenza. Further study is needed to examine whether there is an over- or under-use of anti-influenza drugs in different age groups or regions and to examine the current policy of public use of anti-influenza drugs to reduce influenza-associated morbidity and mortality.

Development and validation of a pharmacy-based comorbidity measure in a population-based automated health care database.

STUDY OBJECTIVE: To develop the Pharmacy-Based Disease Indicator (PBDI), and to evaluate its performance versus the diagnosis-based Deyo version of the Charlson Index in predicting subsequent-year hospitalization in adults. DESIGN: Retrospective cohort analysis. DATA SOURCE: Longitudinal health insurance database derived from the national health insurance system in Taiwan. PATIENTS: Two adult populations were identified: 697,823 individuals who were at least 18 years of age on January 1, 2005 (dataset 2005), and 714,072 who were at least 18 years of age on January 1, 2006 (dataset 2006). MEASUREMENTS AND MAIN RESULTS: Based on the Chronic Disease Score framework and the Anatomical Therapeutic Chemical classification system, we developed the PBDI, a comorbidity measure that is a function of 37 drug categories that correspond to major diseases in Taiwan. The relationship between individuals' PBDI score and subsequent-year hospitalization was evaluated by use of logistic regression models. Covariates in the models included age group, sex, PBDI score, and Deyo score. Using the two overlapping adult populations, we calculated both the PBDI score and the Deyo score for each individual in each year. Using subsequent-year hospitalization as the outcome and each comorbidity measure as the predictor, we demonstrated that the c statistic of the PBDI versus the Deyo version of the Charlson Index was 0.72 versus 0.69 for both the 2005 and 2006 populations. The Akaike information criterion, Bayesian information criterion, model calibration, and reclassification measures also confirmed the utility of the PBDI. CONCLUSION: The PBDI demonstrated acceptable predictive performance for subsequent-year hospitalization. It can be used as a general comorbidity measure to describe the health status of populations based on data derived from population-based automated health care databases.

Management of severe community-acquired septic meningitis in adults: from emergency department to intensive care unit.

BACKGROUND/PURPOSE: To study the clinical features, diagnostic processes, timing of antibiotic administration and outcomes of patients with severe community-acquired septic meningitis at an emergency department (ED), who required intensive care unit (ICU) admission. METHODS: From January 1993 to December 2005, the medical records of patients admitted to the ICU with a diagnosis of community-acquired septic meningitis were reviewed. The clinical characteristics, including causative pathogens, treatment course, and outcomes were collected and analyzed. RESULTS: A total of 40 patients were included, with an overall in-hospital mortality rate of 77.5%. The most common pathogen was Klebsiella pneumoniae (n=20, 50%), followed by Streptococcus pneumoniae (n=6, 15%), and Cryptococcus neoformans (n=5, 12.5%). There was a mean duration of 8.9 hours between ED arrival and initiation of antibiotic therapy. Effective antibiotics were administered for a mean period of 23.8 hours after arrival. Time delay from ED arrival to ICU admission was correlated with time delay of effective antibiotics administration, head computed tomography, and cerebrospinal fluid study (r=0.32, 0.47, and 0.53, respectively; p=0.05, 0.006, and 0.001, respectively). Earlier ICU admission was demonstrated in survivors as compared with those who died (11.1 vs. 38.0 hours, p=0.01). CONCLUSION: Severe septic meningitis remains a disease with high mortality and morbidity. Expeditious diagnostic processes with early appropriate antibiotic treatment and ICU admission at the ED are important in improving the quality of care and patient outcome.