Increased risk of avascular necrosis in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Avascular necrosis (AVN) and psoriasis have some pathogenic mechanisms and associated conditions in common. OBJECTIVE: To examine the association between psoriasis and AVN. METHODS: This study used data from the Taiwan National Health Insurance Research Database for the period 2004-2006 and identified 28,268 patients with psoriasis, who were then matched for age and sex with 113,072 controls without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Multivariate Cox proportional hazards models were used for the analysis. RESULTS: The unadjusted risk of AVN was significantly higher for patients with psoriasis than for controls (hazard ratio [HR] 2.29) and remained significant after adjustment for other risk factors (adjusted HR 1.96; 95% confidence interval 1.62-2.38). The risk for AVN increased in relation to psoriasis severity and was higher for patients with psoriasis and arthritis than for patients without arthritis. The adjusted HRs were higher for male patients than for female patients and for patients younger than 30 years compared with older patients. LIMITATIONS: We lacked information on daily tobacco use, alcohol consumption, and physical activity. CONCLUSION: The risk for AVN increased with the disease severity of psoriasis.

Increased risk of aortic aneurysm (AA) in relation to the severity of psoriasis: A national population-based matched-cohort study.

BACKGROUND: Inflammation of systemic and vascular tissues besides the skin in psoriasis is associated with cardiovascular morbidity and mortality. OBJECTIVE: We sought to investigate whether or not patients with psoriasis have an increased risk of aortic aneurysm (AA). METHODS: This population-based cohort study identified 34,301 patients with psoriasis in the Taiwan National Health Insurance Research Database during 2004 to 2006, who were matched for age and sex with 137,204 control subjects without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Each individual was individually followed up for 5 years to identify those who subsequently developed AA. RESULTS: After adjusting for medical history and medication use, patients with psoriasis were at increased overall risk of AA (adjusted hazard ratio [HR] 1.80; 95% confidence interval 1.25-2.61). The risk for AA increased with the severity of psoriasis. The adjusted HRs were higher for male than female patients (adjusted HR 1.84 vs 1.56), and for patients younger than 50 years versus older patients (adjusted HR 2.81 vs 1.64). LIMITATIONS: There is a lack of information regarding patients' Psoriasis Area and Severity Index score, daily tobacco use, or alcohol consumption. CONCLUSION: Patients with psoriasis are predisposed to developing AA: this risk increases with psoriasis severity and is independent of established cardiovascular risk factors.

Increased risk of arrhythmia in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Psoriasis is associated with cardiovascular morbidity and mortality. However, the association between psoriasis and arrhythmia has not been adequately studied. OBJECTIVE: We sought to investigate whether patients with psoriasis have an increased risk of arrhythmia. METHODS: This population-based cohort study identified 40,637 patients with psoriasis and 162,548 subjects without psoriasis matched by age, sex, history of coronary artery disease, hypertension, and diabetes in the Taiwan National Health Insurance Research Database during 2004 through 2006. RESULTS: After adjusting for medical history and medication use, patients with psoriasis were at increased risk of overall arrhythmia (adjusted hazard ratio [aHR] 1.34; 95% confidence interval [CI] 1.29-1.39). The risks of arrhythmia were higher in all subgroups, including patients with severe (aHR 1.25; 95% CI 1.12-1.39) and mild (aHR 1.35; 95% CI 1.30-1.41) psoriasis, and in patients with (aHR 1.46; 95% CI 1.22-1.74) and without (aHR 1.33; 95% CI 1.28-1.39) psoriatic arthritis. LIMITATIONS: The National Health Insurance Research Database did not contain information regarding Psoriasis Area and Severity Index, cigarette smoking, or alcohol consumption. CONCLUSION: Patients with psoriasis were at higher risk of developing arrhythmia, particularly for those with psoriatic arthritis, independent of traditional cardiovascular risk factors.

Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide retrospective cohort study from Taiwan.

AIMS: To examine the relationship between different anti-diabetic therapies (dipeptidyl peptidase-4 (DPP-4), metformin and sulfonylureas) and risk of acute pancreatitis among type 2 diabetic patients in Taiwan, and explore each drug's dose-response relationship. MATERIALS AND METHODS: We derived a nationwide retrospective cohort of patients with type 2 diabetes in Taiwan. The inclusion criteria are adult diabetic patients with continuous baseline enrollment, new users of the studied drugs, and without missing demographics. There were 4113/101 498/44 772 DPP-4/Metformin/Sulfonylurea users. Adjusted hazards ratios for pancreatitis associated with DPP-4, derived from Cox proportional hazard models with propensity score weighting, were estimated; dose-response analyses were also conducted. RESULTS: Dipeptidyl peptidase-4 was statistically significantly associated with a decreased risk of acute pancreatitis compared with sulfonylureas (adjusted HR: 0.36, 95%CI [0.17, 0.75]) but not metformin (adjusted HR: 0.67, 95%CI [0.32, 1.41]); metformin was statistically significantly associated with a lower risk of pancreatitis than sulfonylurea (adjusted HR: 0. 53; 95%CI [0.37, 0.76]). In addition, low-dose metformin was statistically significantly associated with a lower risk of pancreatitis compared with high-dose metformin (HR: 0.65; 95%CI [0.44, 0.97]). CONCLUSIONS: Our findings suggest that sulfonylureas may potentially be associated with an increased risk of pancreatitis compared with DPP-4 or metformin. Studies with longer follow up, larger sample sizes, and more precise capture of confounders may be needed to determine the risk of pancreatitis associated with incretin based therapies.

Safety of deferasirox: a retrospective cohort study on the risks of gastrointestinal, liver and renal events.

BACKGROUND: Deferasirox (DFX) is an effective and well-tolerated oral iron chelator elevating the adherence to iron chelating therapy among patients with iron overload. However, the US Food and Drug Administration issued a warning about the potential adverse events associated with DFX in 2010. METHODS: To examine the risks of gastrointestinal (GI) bleeding, acute liver necrosis, and acute renal failure among DFX users compared with desferrioxamine (DFO) users in a real-world setting, first-time users of DFX or DFO between 2005 and 2008 in Taiwan's National Health Insurance database were observed in this population-based retrospective cohort study. The risks of different adverse events were individually analyzed by Cox proportional hazards models and adjusted by age, sex, concomitant medications, and prior medical conditions. RESULTS: Deferasirox users had the highest incidence rates of GI bleeding (2.03 per 10 000 patient-days), acute liver necrosis (0.26 per 10 000 patient-days) and acute renal failure (1.45 per 10 000 patient-days) compared with other iron chelator users. Compared with DFO users, DFX users were not associated with the risk of GI bleeding (adjusted HR 1.03, 95% CI 0.61-1.74, p = 0.90) and the risk of acute liver necrosis (adjusted HR 2.13, 95% CI 0.49-9.33, p = 0.32). The association between DFX use and acute renal failure was found to be statistically significant (HR 2.18, 95% CI 1.18-4.02, p = 0.01; adjusted HR 2.41, 95% CI 1.27-4.58, p = 0.01). CONCLUSION: In this study, we found statistically significant higher risk of acute renal failure and non-statistically significant higher risk of GI bleeding and acute liver necrosis associated with DFX use. More researches are warranted to evaluate the association between DFX use and potential adverse events.

The potentially inappropriate prescription of new drug: thiazolidinediones for patients with type II diabetes in Taiwan.

PURPOSE: To examine the potentially inappropriate prescription of thiazolidinediones (TZD). METHODS: Data on TZD prescriptions were collected from Taiwan's National Health Insurance dataset from 2001 to 2006. TZDs were considered inappropriately prescribed when they were prescribed to patients who were (1) under 18 years old, (2) pregnant, who had (3) type 1 diabetes, (4) severe heart failure, (5) hepatic insufficiency, or (6) renal insufficiency and taking TZD + metformin in combination. We aggregated potentially inappropriate prescriptions of TZD for each health-care institution in each month starting from March 2001, when TZD was introduced to Taiwan's market. RESULTS: The potentially inappropriate prescription of TZD increased from 9.41% in 2001 to 12.50% in 2006. Prior inappropriate prescription led to a 0.06% (95%CI: 0.04-0.08) further increase in its later inappropriate prescription. Accumulated months of experience prescribing TZD was found associated with higher proportion of inappropriate prescription of TZD (0.03%, 95%CI: 0.01-0.05). However, it was negatively associated with new incidence of inappropriate prescription of TZD (-0.20, 95%CI: -0.22 to -0.18). The greater the volume of prior TZD prescription (-0.87%, 95%CI: -0.93 to -0.81) and the greater the number of accumulated months since adoption (-0.14%, 95%CI: -0.16 to -0.12), the greater the decrease in rates of new inappropriate prescriptions. CONCLUSIONS: Along with the quick penetration of the new DM drug came an increased possibility that it would be prescribed inappropriately, a trend that persisted over time.

Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome.

BACKGROUND: There is conflicting evidence regarding the potential interaction between clopidogrel and proton pump inhibitors (PPIs), with observational studies suggesting an increased risk of adverse cardiovascular (CV) outcomes and clinical trials suggesting there is no such risk. METHODS: We conducted a retrospective cohort study to assess CV outcomes of 9753 patients taking dual antiplatelet therapy of aspirin plus clopidogrel with or without a PPI after hospitalization for acute coronary syndrome (ACS). Cox proportional hazards models were used to assess our primary endpoint of re-hospitalization for ACS in overall sample and a propensity score matching subsample. RESULTS: Among patients taking clopidogrel plus aspirin, concomitant use of PPI was not associated with the risk of re-hospitalization for ACS (adjusted hazard ratio [HR] 1.12 [95%CI 0.72-1.73]). The findings were consistent in the propensity score matching cohort (adjusted HR 0.82 [95%CI 0.43-1.54]). Compared with PPI nonusers, there is no significant association between each specific PPI users and the risk of re-hospitalization for ACS (adjusted HR; omeprazole 0.96 [95%CI 0.35-2.66], pantoprazole 1.05 [95%CI 0.38-2.92], rabeprazole 0.60 [95%CI 0.17-2.17], esomeprazole 0.31 [95%CI 0.10-0.99], and lansoprazole 0.82 [95%CI 0.32-2.07]). CONCLUSION: In conclusion, this population-based cohort study found that concomitant use of clopidogrel and PPI in patients who received dual antiplatelet therapy after ACS was not associated with risk of ACS re-hospitalization. Together, our study and findings of recently published clinical trials suggest that there was no apparent CV interaction between clopidogrel and PPI in patients who received dual antiplatelet therapy.

Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of thiazolidinediones for diabetes.

BACKGROUND: Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan. METHODS: Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters. RESULTS: Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50). CONCLUSIONS: Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.

The impact of the rare disease and Orphan Drug Act in Taiwan.

The Rare Disease and Orphan Drug Act (the Act) was enacted in 2000 in Taiwan for the facilitation of the research, development, and accessibility of orphan drugs and special nutritional foods; for the prevention and early diagnosis of rare diseases; and for providing intensive care for patients with rare diseases. The aim was to investigate the impact of the Act on the availability and use of orphan drugs in Taiwan in the hope of identifying the remaining challenges and possible solutions to assist future policy making, which may be applicable in other countries as well. The information and statistics for rare diseases and orphan drugs retrieved from the official annual reports and documents were analyzed. There were 225 diseases recognized as rare diseases, and one-third (75/225) of them were congenital metabolic disorders. Among the 110 designated orphan drugs that could apply for listing in the National Health Insurance (NHI) Pharmaceutical Benefits and Reimbursement Scheme, approximately half (62/110) of them were granted marketing authorization. While the NHI program compulsory for all citizens increased patient accessibility to orphan drugs, the rapidly increasing economic burden became an urgent issue for the government. Emerging gene therapies may be the solution to unmet medical needs and also a financial obstacle to tackle. The Act increased the availability of orphan drugs while the NHI system facilitated patient access, which benefited many patients with rare diseases in Taiwan. However, the soaring economic burden was noticed and was anticipated to aggravate. More communication and cooperation between stakeholders is critical in finding solutions for the long-term sustainability of the NHI system.

Relationship between cumulative dose of thiazolidinediones and clinical outcomes in type 2 diabetic patients with history of heart failure: a population-based cohort study in Taiwan.

BACKGROUND: Thiazolidinediones (TZDs) are widely used antidiabetic agents, but there is great concern and conflicting reports over their possible effect on cardiovascular morbidity, especially in patients with heart failure (HF). METHODS: Using 2000-2005 Taiwan's National Health Insurance (NHI) claims data, this population-based, retrospective cohort study investigated if there was an association between the cumulative TZD dose and clinical outcomes in type 2 diabetic patients recently hospitalized for HF. Study outcomes were death, first all-cause readmission, and first readmission for HF. Cox proportional hazard models were used to analyze the association between TZD versus sulfonylurea (SU) use and these outcomes. RESULTS: Out of a total of 8139 eligible patients, 224 were taking TZD (65.63% female; mean [SD] age, 68.30[10.60] years) and 7915 were taking SU (55.10% female; 70.30[10.50] years). Patients taking TZD were at higher risk for readmission for HF (59 cases; HR 1.58 (95% confidence interval, 95%CI 1.44-1.72)), all-cause readmission (147 cases; 1.40 (1.30-1.70)), and death (103 cases; 2.23 (1.58-3.14)). The higher the cumulative exposure to TZD, the greater the risk of HF readmission, all-cause readmission, and death. CONCLUSION: Among diabetic patients who had been hospitalized for HF, TZD users were at significantly greater risk for readmission for HF, all-cause readmission, and death than SU users. The risk of all adverse clinical outcomes appeared to highly relate to cumulative exposure to TZD. These findings provide empirical evidence supporting the latest black box warnings issued by the United States Food and Drug Administration in August, 2007 advising that TZD not be prescribed for diabetic patients with symptomatic heart failure.

Price regulation, new entry, and information shock on pharmaceutical market in Taiwan: a nationwide data-based study from 2001 to 2004.

BACKGROUND: Using non-steroidal anti-inflammatory drugs (NSAIDs) as a case, we used Taiwan's National Health Insurance (NHI) database, to empirically explore the association between policy interventions (price regulation, new drug entry, and an information shock) and drug expenditures, utilization, and market structure between 2001 and 2004. METHODS: All NSAIDs prescribed in ambulatory visits in the NHI system during our study period were included and aggregated quarterly. Segmented regression analysis for interrupted time series was used to examine the associations between two price regulations, two new drug entries (cyclooxygennase-2 inhibitors) and the rofecoxib safety signal and expenditures and utilization of all NSAIDs. Herfindahl index (HHI) was applied to further examine the association between these interventions and market structure of NSAIDs. RESULTS: New entry was the only variable that was significantly correlated with changes of expenditures (positive change, p = 0.02) and market structure of the NSAIDs market in the NHI system. The correlation between price regulation (first price regulation, p = 0.62; second price regulation, p = 0.26) and information shock (p = 0.31) and drug expenditure were not statistically significant. There was no significant change in the prescribing volume of NSAIDs per rheumatoid arthritis (RA) or osteoarthritis (OA) ambulatory visit during the observational period. The market share of NSAIDs had also been largely substituted by these new drugs up to 50%, in a three-year period and resulted in a more concentrated market structure (HHI 0.17). CONCLUSIONS: Our empirical study found that new drug entry was the main driving force behind escalating drug spending, especially by altering the market share.

Psoriasis is associated with a greater risk for cardiovascular procedure and surgery in patients with hypertension: A nationwide cohort study.

Psoriasis increases the incidence of hypertension and cardiovascular disease. However, its effect on the course of cardiovascular disease remains unknown. To investigate whether patients with psoriasis and hypertension have a higher requirement for cardiovascular procedure and surgery than patients with hypertension but without psoriasis, we used the Taiwan National Health Insurance Research Database to identify patients with new-onset hypertension during 2005-2006. Among these patients, those with psoriasis (n = 4039) were matched in a 1:1 ratio by age and sex with patients without psoriasis. The association between psoriasis and cardiovascular interventions was examined using time-varying Cox proportional hazards models. The mean follow-up period was 5.62 years. Psoriasis was associated with an increased risk for cardiovascular procedure and surgery in patients with hypertension (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.07-1.53). When no psoriasis served as a reference group, the aHRs were higher for women than for men, and for patients aged 50-64 years than for younger and older patients. Patients with severe psoriasis or psoriatic arthritis tended to have higher risks of cardiovascular procedure and surgery than patients with mild psoriasis (aHR, 1.22; 95% CI, 0.98-1.51) or patients without psoriatic arthritis (aHR, 1.15; 95% CI, 0.84-1.58), respectively, did, although not reaching statistical significance. In conclusion, patients with hypertension and psoriasis had a greater requirement for cardiovascular interventions than hypertensive patients without psoriasis. More intense assessments for cardiovascular interventions may be necessary in patients with concurrent hypertension and psoriasis than general hypertension patients.

Hormone therapy use and prescription durations of menopausal women in Taiwan: a 5 years' National Cohort study.

OBJECTIVES: To describe the prevalence and associated factors of hormone replacement therapy (HRT)-related utilization in a national representative fixed cohort in Taiwan. METHOD: The study population are women aged 40 years and over in Taiwan. Our data, provided by National Health Research Institutes, are the sampled registry information of 37,315 beneficiaries of National Health Insurance from 2000 to 2004. The dependent variables were HRT-related utilizations, including physician contact, HRT utilization rate/duration/patterns (new, prevalent and discontinue users). The independent variables were age, time, prior co-morbidities and prior utilization pattern. We used generalized estimating equation (GEE) model for repeated measurement analysis. RESULTS: The outpatient contact rates for menopause syndrome were low, though the HRT prescription rate among those who have contact were high. GEE shows that age, time, prior co-morbidities/HRT utilization patterns were significantly associated with all types of HRT-related utilizations, which all declined significantly following the publications of Women's Health Initiative (WHI) in 2002. The magnitudes of reduction, though similar in 2003-2004, were greater for physician contact and HRT durations than that of HRT prescription rate for those have contacts in 2002. Besides, the percentages of new (discontinue) users have already declined (increased) since 2001 although it had not declined until 2003 for the continued users. CONCLUSIONS: WHI publications have great impact on HRT-related utilizations. However, the response of the women was quicker and much drastic than that of the physicians in 2002. Besides, the efforts of the various women's associations before WHI might have some contribution to the declined (increased) of new (discontinued) users.

Changes of the prescription of hormone therapy in menopausal women: an observational study in Taiwan.

BACKGROUND: To evaluate the impact of the 2002 Women's Health Initiative (WHI) study results on the prescription of menopausal hormone therapy (MHT) to treat menopause-related symptoms in Taiwan. METHODS: This retrospective study participant data collected from women interviewed in 2001 Taiwan's National Health Interview Survey (NHIS) and the National Health Insurance (NHI) outpatient claims for women being treated for menopause-related symptoms. We compared prescriptions made for MHI to women seeking outpatient treatment for menopause-related symptoms before and after the publication of the 2002 WHI to study its effect of prescription behavior in Taiwan. There was one dichotomous outcome variable, which was whether MHT was prescribed or not in an outpatient visit to treat menopause-related symptoms. RESULTS: Our study included 504 women 45 years old or above whose outpatient visits for menopause-related symptoms were covered by National Health Insurance in 2002. In total, these 504 women made 2549 outpatient visits to be treated for these symptoms. The proportion of outpatient visits in which MHT was prescribed dropped from 83.0% (n = 1,155) before WHI to 73.0% (n = 844) after WHI. We found a decrease in likelihood that women would be prescribed MHT for menopause-related symptoms after the release of the WHI report (OR = 0.36, 95% CI = 0.25 to 0.52, p < 0.05). Gynecologists and obstetricians are more likely to prescribe MHT than physicians with other medical specialties (5.34; 95% CI = 3.45 to 8.26, p < 0.05). Women with college level educations or higher became less likely to be prescribed MHT (Model 2; OR 0.30; 95% CI 0.11-0.83), and academic medical centers became less likely to prescribe MHT than other medical care institutions (Model 3; OR 0.15; 95% CI 0.34-0.63). CONCLUSION: The WHI report caused a substantial decline in the use of MHT to treat menopause-related symptoms in Taiwan. It was found to exert most of its influence in patients with higher educations, physicians with specialties other than gynecologists and obstetricians, and academic medical centers.

Cardiovascular events associated with long-term use of celecoxib, rofecoxib and meloxicam in Taiwan: an observational study.

BACKGROUND: Using national data (2001-2003), this study explored the risk of acute myocardial infarction (AMI), angina, stroke and transient ischaemic attack (TIA) in long-term users of rofecoxib and celecoxib in Taiwan and compared this data with that for those using meloxicam. METHODS: Patients included in the study had used celecoxib, rofecoxib or meloxicam for at least 180 days. Data were taken from National Health Insurance database for the period from 2001 to 2003. Main outcome measurements were the occurrence of AMI, angina, stroke or TIA after the initiation of long-term continuous use of these drugs. Person-time exposures and hazard ratios (HRs) were calculated based on data from 9602 eligible patients. RESULTS: In patients without a history of a cardiovascular event within the year before drug treatment began, the overall rates of AMI, angina, stroke and TIA were 1.1%, 0.6%, 2.0% and 0.6%, respectively. In those with cardiovascular events in the year before treatment began, the overall rates of AMI, angina, stroke and TIA were 5.0%, 4.8%, 6.6% and 5.8%, respectively. Compared with meloxicam users, celecoxib users had lower HRs for the development of AMI (HR 0.78, 95% CI 0.63, 0.96) and stroke (HR 0.81, 95% CI 0.70, 0.93). Rofecoxib users were at no higher risk of cardiovascular events than those receiving meloxicam. Regardless of treatment, having had a cardiovascular event in the year before treatment began played a significant role in the development of the same cardiovascular event during the prescription period; the HRs associated with having had the same cardiovascular event in the past year, versus not having had such an event, were 3.02 (95% CI 1.44, 6.32) for AMI, 5.82 (95% CI 3.19, 10.63) for angina, 2.44 (95% CI 1.79, 3.33) for stroke and 7.16 (95% CI 3.70, 13.87) for TIA. CONCLUSIONS: Patients taking celecoxib had a lower risk of cardiovascular events than those taking meloxicam. Patients taking rofecoxib were not found to be at higher cardiovascular risk than those taking meloxicam. The most significant determinant of cardiovascular risk was a history of such cardiovascular disease in the year preceding treatment initiation. Patients with a history of other medical conditions also appeared to be at higher risk of adverse cardiovascular events.

Cardiovascular events associated with the use of four nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) versus a cyclooxygenase-2 inhibitor (celecoxib): a population-based analysis in Taiwanese adults.

BACKGROUND: Serious cardiovascular events (CVEs) have been linked to the use of cyclooxygenase (COX)-2 inhibitors, a category of selective NSAIDs. However, few studies are available that have compared the risk for CVEs between COX-2 inhibitors and nonselective NSAIDs in adults undergoing long-term treatment. OBJECTIVES: The present study assessed (1) whether long-term use of nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) is associated with an increased risk for treatment-related CVEs (acute myocardial infarction [AMI], angina, cerebrovascular attack [CVA], and/or transient ischemic attack [TIA]) compared with long-term use of celecoxib and (2) which factors are associated with the risk for treatment-related CVEs in long-term users of nonselective NSAIDs in Taiwan. METHODS: This population-based analysis used data from the Taiwanese Bureau of National Health Insurance (Taipei, Taiwan) database. Eligible patients were aged > or = 18 years and had been receiving etodolac, nabumetone, ibuprofen, naproxen, or celecoxib for > or = 180 days between January 1, 2001, and December 31, 2003. The primary outcomes measure was the prevalence of serious CVEs (AMI, angina, CVA, and/or TIA requiring hospitalization) after initiation of treatment. Analyses were performed on data from all eligible patients; person-time exposures to the drugs and hazard ratios (HRs) were calculated to determine the risk for CVEs with long-term use. RESULTS: A total of 16,326 patients (8166 men, 8160 women; mean [SD] age, 61.83 [20.23] years) who had received long-term treatment with etodolac (2014 [12.34%]), nabumetone (2262 [13.86%]), ibuprofen (5239 [32.09%]), naproxen (3049 [18.68%]), or celecoxib (3762 [23.04%]) were identified. The overall prevalences of AMI, angina, CVA, and TIA were higher in long-term users with a history of cardiovascular disease (CVD) than in those without (AMI, 4.76% vs 0.99%; angina, 4.11% vs 0.43%; CVA, 7.74% vs 1.51%; and TIA, 4.03% vs 0.52%) (all, P < 0.01). The HRs for AMI, angina, CVA, and TIA were not significantly different between the NSAID and celecoxib groups. History of CVD played a significant role in recurrence during the period studied; the HRs (95% CIs) were 2.29 (1.22-4.32) for AMI, 6.19 (3.56-10.78) for angina, 3.56 (2.80-4.52) for CVA, and 6.60 (3.72-11.73) for TIA. Preexisting medical conditions (hypertension, dyslipidemia, diabetes mellitus, congestive heart failure, chronic renal disease) also significantly affected the risk for CVEs. CONCLUSIONS: In this cohort study of long-term (> or = 180 days) use of NSAIDs in Taiwanese adults, no significant differences in the risk for treatment-related CVEs were observed between groups prescribed 1 of 4 nonselective NSAIDs (etodolac, nabumetone, ibuprofen, or naproxen) or celecoxib. History of CVD was the most significant determinant of CVE risk. Patients with preexisting medical conditions appeared to have a significantly higher risk for CVEs associated with the use of NSAIDs and celecoxib compared with patients without these conditions.

The Risk of Chronic Pancreatitis in Patients with Psoriasis: A Population-Based Cohort Study.

BACKGROUND: Psoriasis is a chronic systemic inflammatory disorder, and studies have revealed its association with a variety of comorbidities. However, the risk of chronic pancreatitis (CP) in psoriasis has not been studied. This study aimed to investigate the risk of CP among patients with psoriasis. METHODS: Using the Taiwan National Health Insurance Research Database, this population-based cohort study enrolled 48430 patients with psoriasis and 193720 subjects without psoriasis. Stratified Cox proportional hazards models were used to compare the risks of CP between the patients with and without psoriasis. RESULTS: The incidence of CP was 0.61 per 1000 person-years in patients with psoriasis and 0.34 per 1000 person-years in controls during a mean 6.6-year follow-up period. Before adjustment, patients with psoriasis had a significantly higher risk of CP (crude hazard ratio (HR) = 1.81; 95% confidence interval (CI) = 1.53-2.15), and the risk remained significantly higher after adjustments for gender, age group, medications, and comorbidities (adjusted HR (aHR) = 1.76; 95% CI = 1.47-2.10). All psoriasis patient subgroups other than those with arthritis, including those with mild and severe psoriasis and those without arthritis, had significantly increased aHRs for CP, and the risk increased with increasing psoriasis severity. Psoriasis patients taking nonsteroidal anti-inflammatory drugs (aHR = 0.33; 95% CI = 0.22-0.49) and methotrexate (aHR = 0.28; 95% CI = 0.12-0.64) had a lower risk of developing CP after adjustments. CONCLUSIONS: Psoriasis is associated with a significantly increased risk of CP. The results of our study call for more research to provide additional insight into the relationship between psoriasis and CP.

Concomitant Sleep Disorders Significantly Increase the Risk of Cardiovascular Disease in Patients with Psoriasis.

BACKGROUND: The increased rates of cardiovascular morbidity and mortality in patients with psoriasis are not adequately explained by traditional risk factors. Whether concomitant sleep disorders (SDs) modify the risk of cardiovascular disease (CVD) in patients with psoriasis remains unknown. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), we conducted a cohort study to investigate the association between concomitant SDs and CVD risk in patients with psoriasis. Data from 99,628 adults who received a psoriasis diagnosis during the period from 2004 to 2010 were analyzed. Cox proportional hazards regression analysis models were used to compare the risks of ischemic heart disease (IHD) and stroke between patients with and without SDs. RESULTS: Psoriasis patients with a concomitant SD had significantly higher risks of IHD (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 1.22-1.28) and stroke (aHR, 1.24; 95% CI, 1.16-1.33) as compared with psoriasis patients without SDs. All psoriasis patient subgroups, including those with mild and severe psoriasis and those with and without arthritis, had increased HRs for IHD and stroke. The increases in IHD and stroke risks conferred by SDs were proportional to the dose of hypnotics used. The effect of SDs on the risks of IHD and stroke was greater in young adults than in middle-aged and older adults. CONCLUSIONS: The risks of IHD and stroke were higher for psoriasis patients with SDs than for those without SDs. Clinicians should carefully evaluate CVD risk, particularly in young patients with psoriasis.

Risk of fractures in vitiligo patients treated with phototherapy-A retrospective population-based cohort study.

BACKGROUND: Phototherapy might increase bone mineral density. However, it is unknown whether phototherapy can reduce the risk of fractures in patients with vitiligo. OBJECTIVES: To investigate the effect of phototherapy on fracture risks in vitiligo patients aged 40 or older. METHODS: This population-based cohort study used the 2000-2010 Taiwan National Health Insurance Research Database (NHIRD) to identify 3863 patients newly diagnosed with vitiligo between 2003 and 2009 at age ≥40 years. Study subjects were classified into three cohorts: (1) frequent phototherapy; (2) infrequent phototherapy; and (3) no phototherapy. Patients were followed until the first hip or vertebral fracture or 31 December 2010. Data were analysed using Cox regression models and also stratified by age and gender. RESULTS: Frequent phototherapy decreased the fracture risks (adjusted hazard ratio (aHR)=0.32, p=0.009) in vitiligo patients. Stratification by age and gender confirmed the fracture prevention effect of frequent phototherapy in patients aged 40-64 years (aHR=0.14, p=0.016) and in female patients (aHR=0.31, p=0.024). CONCLUSIONS: This study provides the first evidence that frequent phototherapy can reduce the risk of fractures among middle-aged and among female vitiligo patients.

Patterns of sleep-related medications prescribed to elderly outpatients with insomnia in Taiwan.

OBJECTIVE: To explore prescription patterns and determinants of sleep-related medications prescribed to elderly outpatients with insomnia in Taiwan. METHODS: This cross-sectional study was based on 2001 annual outpatient claims data released by the Bureau of National Health Insurance in Taiwan. The claims data of each physician consultation were extracted and merged in one claim file. International Classification of Diseases (9th Edition)-Clinical Modification codes, patient's demographics, physician's specialty, the medical institution code and the content of pharmaceutical prescription constituted a file. Patients were included if they were: (i) > or =65 years of age; and (ii) coded as having 'insomnia'. RESULTS: Elderly insomniacs made up 216,994 of the 1,000,193 outpatient claim files we surveyed. Patients had a mean age of 74.33 years, and the sex distribution was nearly equal. Based on the data above, 11.14% of the elderly had been diagnosed as having 'insomnia' for the year 2001. This population preferred primary-care clinics over hospital-ambulatory departments; patients most frequently sought medical help from internal medicine specialists. The most popular sleep medication was lorazepam, followed by zolpidem. The first-choice off-label drug used to treat insomnia was trazodone. Hypnotics, sedatives and anxiolytics were prescribed 12.6 times more frequently than off-label used drugs. When treating insomnia with an off-label drug, physicians usually prescribed a therapeutic dosage much lower than that recommended in the package insert. Choice of sleep medication and off-label drug were most often influenced by physician specialty. Off-label prescriptions were common but not prevalent. Choice of hypnotic or sedative-anxiolytic was related to how long the drug acted and how much it cost; choice of off-label drug was related to physicians' familiarity with specific drugs and patients' characteristics. Concomitant anxiety or depression was significantly associated with higher consumption of hypnotics. CONCLUSIONS: Benzodiazepines and newer non-benzodiazepine hypnotics are still the most frequently used drugs for treating insomnia in the elderly in Taiwan. Elderly patients with concomitant anxiety or depression consumed more hypnotics. Further studies conducted over several years are needed to identify trends in the pharmacological treatment of insomnia.