Hsin-Hua Chen

Association between a history of periodontitis and the risk of rheumatoid arthritis: a nationwide, population-based, case–control study

Objective To investigate the association between the risk of rheumatoid arthritis (RA) and a history of periodontitis. Methods This nationwide, population-based, case–control study used administrative data to identify 13 779 newly diagnosed patients with RA (age ≥16 years) as the study group and 137 790 non-patients with RA matched for age, sex, and initial diagnosis date (index date) as controls. Using conditional logistic regression analysis after adjustment for potential confounders, including geographical region and a history of diabetes and Sjögrens syndrome, ORs with 95% CI were calculated to quantify the association between RA and periodontitis. To evaluate the effects of periodontitis severity and the lag time since the last periodontitis visit on RA development, ORs were calculated for subgroups of patients with periodontitis according to the number of visits, cumulative cost, periodontal surgery and time interval between the last periodontitis-related visit and the index date. Results An association was found between a history of periodontitis and newly diagnosed RA (OR=1.16; 95% CI 1.13 to 1.21). The strength of this association remained statistically significant after adjustment for potential confounders (OR=1.16; 95% CI 1.12 to 1.20), and after variation of periodontitis definitions. The association was dose- and time-dependent and was strongest when the interval between the last periodontitis-related visit and the index date was <3 months (OR=1.64; 95% CI 1.49 to 1.79). Conclusions This study demonstrates an association between periodontitis and incident RA. This association is weak and limited to lack of individual smoking status.

Diagnostic value of procalcitonin for differentiation between bacterial infection and non-infectious inflammation in febrile patients with active adult-onset Still's disease.

Adult-onset Still’s disease (AOSD) has been recognised as an important cause of fever of unknown origin. Over 99% of AOSD patients displayed fever during their disease course.1 The diagnosis of bacterial infection in febrile AOSD patients is challenging because traditional markers of infection are often misleading. This prompted us to search for a reliable marker that allows early discrimination between non-infectious inflammation and bacterial infection in febrile AOSD patients. Procalcitonin, a novel marker that can distinguish disease activity from infection, has been investigated in febrile patients with systemic lupus erythematosus (SLE).2 3 Procalcitonin has proved to be a diagnostic marker of infection in critically ill patients compared with other inflammatory parameters.4 Serum procalcitonin is normally undetectable (<0.05 ng/ml) and procalcitonin levels of 0.5 ng/ml or greater can distinguish infection from non-infectious inflammation.3 5 Contradictory results for procalcitonin have recently been reported in …

Risk of herpes zoster in patients with systemic lupus erythematosus: a three-year follow-up study using a nationwide population-based cohort

OBJECTIVE: The goal of the present study was to estimate the risk ratio of herpes zoster among systemic lupus erythematosus patients after disease onset compared with a cohort of patients without systemic lupus erythematosus over a three-year period. METHODS: A nationwide population-based cohort study using the National Health Insurance Research Database identified 10,337 new cases of systemic lupus erythematosus as the study cohort. In addition, 62,022 patients without systemic lupus erythematosus, who were matched for age, gender, and date of systemic lupus erythematosus diagnosis, were used as the comparison cohort. These cohorts were followed-up for three years. A Cox proportional hazard regression was performed to estimate the risk ratio of herpes zoster, with adjustments for age, gender, level of insurance, urbanization level, geographic region, comorbid medical conditions, average daily dosage of corticosteroids, and the use of immune-modulation agents. RESULTS: Compared to patients without systemic lupus erythematosus, the crude risk ratio and adjusted risk ratio of herpes zoster among systemic lupus erythematosus patients were 7.37 (95% confidence interval 6.75-8.04) and 2.45 (95% confidence interval 1.77-3.40), respectively. Stratified by gender, the adjusted risk ratio of herpes zoster was 2.10 (95% confidence interval 1.45-2.99) in women and 7.51 (95% confidence interval 2.89-19.52) in men. Stratified by age, the adjusted risk ratio peaked in systemic lupus erythematosus patients who were aged 18 to 24 years (risk ratio 8.78, 95% confidence interval 3.08-24.97). CONCLUSION: Based on nationwide population-based data, there is an increased risk of herpes zoster in systemic lupus erythematosus patients compared with non-systemic lupus erythematosus patients, particularly among males and patients aged 18 to 24 years. Further research on the associated risk factors for herpes zoster in systemic lupus erythematosus patients is needed.

Dipeptidyl Peptidase-4 Inhibitors and the Risk of Acute Pancreatitis in Patients With Type 2 Diabetes in Taiwan: A Population-Based Cohort Study.

AbstractTo investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the risk of acute pancreatitis in patients with type 2 diabetes.This nationwide population-based cohort study used the diabetes patients dataset of Taiwans National Health Research Insurance Research Database. Patients with newly diagnosed type 2 diabetes between January 1, 2008 and December 31, 2009 and no history of acute pancreatitis were selected. This cohort was followed from the index date to the onset of acute pancreatitis or December 31, 2011. The main outcome measure was the hazard ratio (HR) for acute pancreatitis associated with DPP-4 inhibitor use. Cox proportional-hazards regression analyses were adjusted for alcohol use, hypertriglyceridemia, cholelithiasis, neoplasm, and Diabetes Complications Severity Index (DCSI) score. Subgroup analyses stratified by age and sex were conducted.The study cohort comprised 114,141 patients. Significant interaction effects were observed between sex and age (HR 0.80, 95% confidence interval [CI] 0.64–0.99) and age and DCSI score (HR 0.83, 95% CI: 0.71–0.97). In subgroup analyses, significant risks of acute pancreatitis were noted in female and elderly DPP-4 inhibitor users. Among women, the risk of acute pancreatitis was significantly higher among DPP-4 inhibitor users than among nonusers (HR 2.27, 95% CI: 1.30–3.97). This risk was also significantly higher in users than in nonusers among patients aged >65 years (HR 2.39, 95% CI: 1.11–5.15).Female and elderly DPP-4 inhibitor users had significantly elevated risks of acute pancreatitis development. Further well-conducted studies are needed to confirm our findings.

Gender differences in ankylosing spondylitis-associated cumulative healthcare utilization: a population-based cohort study.

BACKGROUND: Ankylosing spondylitis (AS) is one of the most common rheumatic diseases with gender differences in prevalence and clinical presentation. This study aimed to examine whether such gender differences are correlated with cumulative healthcare utilization in Taiwan. METHODS: The National Health Insurance Research Database supplied claim records of one million individuals from 1996 to 2007. Selected cases included patients aged ≥16 years. Certified rheumatologists diagnosed the patients in three or more visits and gave prescriptions for AS. Multivariate adjusted logistic regression analyses were used to calculate the influence of gender on cumulative healthcare utilization associated with AS. RESULTS: The study included 228 women and 636 men. After adjustment for potential confounding factors, men had more cumulative outpatient visits associated with AS (odds ratio, 1.59; 95% confidence interval, 1.13 -2.23; p = 0.008). Men also exhibited a trend for higher frequency of AS-related hospitalization (p = 0.054). CONCLUSION: Men are more likely to have high cumulative AS-associated healthcare utilization than women. Further investigation of the causal factors is warranted.

Periodontitis and etanercept discontinuation risk in anti-tumor necrosis factor-naive rheumatoid arthritis patients: a nationwide population-based cohort study.

ObjectiveThe objective of this study was to investigate the association between periodontitis (PD) and etanercept (ETN) discontinuation in anti–tumor necrosis factor (anti-TNF)–naive patients with rheumatoid arthritis (RA). MethodsThis retrospective nationwide population-based cohort study identified 3359 anti-TNF–naive patients with RA (age at diagnosis ≥16 years) in whom ETN treatment was initiated using administrative data. We identified PD exposure within 5 years before ETN initiation and during ETN treatment. Cox proportional hazard models were used to assess ETN discontinuation risk associated with PD within 5 years before ETN initiation, shown as hazard ratios with 95% confidence intervals (CIs). Stratified analyses were performed on the basis of PD during ETN treatment to avoid violating the Cox regression assumptions. ResultsPatients with PD history during the 5 years before ENT initiation had a higher risk of ETN discontinuation compared with those without such history; the hazard ratios of ETN discontinuation were 1.27 (95% CI, 1.01–1.60) and 1.17 (95% CI, 1.06–1.30) among patients with and without PD during ETN treatment, respectively. Other risk factors included age older than 65 years and daily prednisolone dose greater than 10 mg/d within 1 year before ETN initiation. Concomitant methotrexate, leflunomide, salazopyrin, or hydroxychloroquine administration had a protective effect on ETN discontinuation in patients without PD during ETN treatment, but the protective effect by leflunomide, salazopyrin, and hydroxychloroquine was attenuated in patients with PD during ETN treatment (P for interaction <0.05). ConclusionsA PD history within 5 years before ETN administration was associated with increased ETN discontinuation risk in anti-TNF–naive patients with RA.

The Incidence and Prevalence of Thromboangiitis Obliterans in Taiwan: A Nationwide, Population-based Analysis of Data Collected from 2002 to 2011

OBJECTIVE: To estimate the incidence and prevalence of thromboangiitis obliterans in Taiwan in the period spanning from 2002 to 2011. METHODS: We identified all incident and prevalent cases with a diagnosis of thromboangiitis obliterans (International Classification of Diseases, Ninth Revision code 443.1) in the period spanning from 2002 to 2011 using Taiwan’s National Health Insurance Research Database. We calculated the age- and sex-specific incidence and prevalence rates of thromboangiitis obliterans during the study period. RESULTS: From 2002 to 2011, 158 patients were diagnosed with thromboangiitis obliterans; of these, 76% were men. Most (63%) of the patients were <50 years old when they were first diagnosed. After reaching 20 years of age, the incidence rate increased with age and peaked among those aged ≥60 years. The average incidence rate of thromboangiitis obliterans during the 2002–2011 period was 0.068 per 105 years. The incidence of thromboangiitis obliterans decreased with time, from 0.10 per 105 years in 2002 to 0.04 per 105 years in 2011. The prevalence increased from 0.26 × 10−5 in 2002 to 0.65 × 10−5 in 2011. CONCLUSION: This is the first epidemiologic study of thromboangiitis obliterans using claims data from a general population in Taiwan. This nationwide, population-based study found that the incidence and prevalence of thromboangiitis obliterans in Taiwan in the 2002–2011 period were lower than those in other countries before 2000. This study also revealed a trend of decreasing incidence with simultaneous increasing prevalence of thromboangiitis obliterans in Taiwan from 2002 to 2011.

The association between glaucoma and risk of depression: a nationwide population-based cohort study

BackgroundPrevious cross-sectional studies revealed a higher prevalence of depression among glaucoma patients. However, cohort studies were in lack to build the risk of incident depression after the diagnosis of glaucoma. The aim of our study was to investigate the association between glaucoma and the subsequent risk of developing depression and to assess risk factors associated with depression in glaucoma patients.MethodsA population-based retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from January 1, 2001 through December 31, 2011. Glaucoma patients (n = 8777) and age- and gender-matched control subjects without glaucoma (n = 35,108) were enrolled in the study. Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent depression between the glaucoma and control groups. A Cox regression analysis estimated the crude and adjusted hazard ratios (HRs) for depression. Risk factors leading to depression were investigated among the glaucoma patients.ResultsGlaucoma patients had a significantly higher cumulative hazard of depression compared to the control group (p-value < 0.0001). The Cox regression model indicated that the glaucoma group had a significantly higher risk of depression (adjusted HR = 1.71). Within the glaucoma group, significant risk factors for depression included age, female, low income, substance abuse, and living alone. However, the use of β-blocker eye drops and the number of glaucoma medications were not significant risk factors for depression.ConclusionPatients with glaucoma are at significantly greater risk of developing depression. Among glaucoma patients, age, female, low income, substance abuse, and living alone were significant risk factors for depression.

FRI0574 One-Year Tuberculosis Risk in Rheumatoid Arthritis Patients Initiating Tumor Necrosis Factor-α Inhibitor from 2003 To 2011 in Taiwan: A Nationwide Population-Based Cohort Study

Background Use of tumor necrosis factor-α inhibitor (TNFi), especially monoclonal antibody, may increase the risk of tuberculosis (TB) infection in patients with rheumatoid arthritis (RA). The emergence of active TB in RA patients receiving TNF-α inhibitor showed a biphasic pattern. The strategy of latent TB infection (LTBI) screening and treatment theoretically may reduce TB reactivation, which mainly contributes to the first phase of TB emergence. In Taiwan, etanercept and adalimumab were approved for RA treatment in 2003 and 2007 respectively. Objectives To examine the 1-year risk of TB infection in RA patients initiating TNFi therapies as compared to RA patients not treated with TNFi in Taiwan stratified by treatment initiation year (2003 to 2011). Methods Data was collected retrospectively using the 2003–2012 claim data from the Taiwanese National Health Insurance Research Database. We enrolled all treated RA patients initiating TNFi therapy as the study cohort, and those who never received TNFi therapy as the comparison cohort from 1st January 2003 to 31st December 2011. All patients were followed up for one year after starting treatment. The diagnosis of TB was identified using ICD-9-CM and the prescription of at least 2 anti-TB drugs within 6 months of TB diagnosis made. The 1-year TB risk of TNFi users compared with non-TNFi users was shown as incident rate rations (IRR) with 95% confidence intervals (CI) and adjusted hazard ratios (aHRs) using Coxs regression analysis after adjustment of potential confounders including age, sex, disease duration, TB history, comorbidities and concomitant medications, further stratified by the year of treatment initiation. Results A total of 46,668 RA patients were included; 40,678 (87.2%) in non-TNFi and 5,990 (12.8%) in TNFi group. A total of 163 1-year TB events were reported; 136 in non-TNFi group and 27 in TNFi group with 1-year TB incidence rate of 369 and 504 per 100,000 patient-years respectively. The 1-year TB risk was higher in TNFi users compared with non-TNFi users (IRR, 1.37; 95% CI, 0.71–2.07; aHR, 7.27; 95% CI, 3.65- 14.48). As shown in Figure 1, the IRR of TB within one year in adalimumab users compared with non-TNFi users peaked in 2008 (IRR, 4.57) and was lowest in the 2011 group (IRR, 0.49). Other significant risk factors of 1-year TB infection included age≥65 years (aHR, 1.52, 95% CI, 1.09–2.10), male (aHR, 1.81, 95% CI, 1.31–2.51) and prior TB infection (aHR, 29.28; 95% CI, 18.62–46.05). Conclusions The 1-year risk of TB in RA patients initiating TNFi was significantly higher than non-TNFi users. During 2008–2011, the 1-year TB IRR in adalimumab users compared with non-TNFi users dropped from 4.57 to 0.49, which might be explained by increasing physician/patient awareness with LTBI screening and treatment. References Chen DY, Shen GH, Chen YM, Chen HH, Hsieh CW, Lan JL. Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFalpha inhibitors: the utility of IFNgamma assay. Annals of the rheumatic diseases. 2012;71(2):231–7. Disclosure of Interest H.-H. Chen Grant/research support from: AbbVie Biopharmaceuticals GmbH Taiwan Branch, Y.-M. Chen: None declared, K.-L. Lai: None declared, C.-H. Lin: None declared, D.-Y. Chen: None declared, C.-H. Lim: None declared, C.-J. Tsai: None declared

SAT0584 The Incidence and Prevalence of Thromboangiitis Obliterans in Taiwan: A Nationwide, Population-Based Analysis of Data during 2002–2011

Background Thromboangiitis obliterans (TAO) is a nonatherosclerotic segmental inflammatory disease that most commonly affects the small and medium-sized arteries, veins, and nerves of the arms and legs. Most epidemiologic studies were conducted using hospital-based data, and only few population-based epidemiologic studies of TAO have been published. Objectives To estimate the incidence and prevalence of thromboangiitis obliterans (TAO) in Taiwan during 2002 to 2011. Methods We identified all patients with a diagnosis of TAO (International Classification of Diseases, Ninth Revision code 443.1) in Taiwans National Health Insurance Research Database from January 2002 to December 2011. We calculated the age- and sex-specific incidence and prevalence rates of TAO during the study period. Results During 2002–2011, 158 patients were diagnosed with TAO; of these, 76% were men. Most (63%) patients were <50 years of age when they were first diagnosed. After attaining 20 years of age, the incidence rate increased with age and peaked among those aged ≥60 years. The average incidence rate of TAO during 2002–2011 was 0.068 per 105 years. The incidence of TAO decreased with time: from 0.10 per 105 years in 2002 to 0.04 per 105 years in 2011. The prevalence increased from 0.26×10–5 in 2002 to 0.65×10–5 in 2011. Age group Case number Person-years Incidence rate† F M T F M T F M T 0–9 1 2 3 19050837 20763899 39814736 0.01 0.01 0.01 10–19 1 0 1 16112069 17223717 33335786 0.01 0.00 0.00 20–29 7 20 27 20335969 19005493 39341462 0.03 0.11 0.07 30–39 1 30 31 19137215 19243068 38380283 0.01 0.16 0.08 40–49 8 29 37 17444626 17434089 34878714 0.05 0.17 0.11 50–59 5 17 22 10321223 10007057 20328281 0.05 0.17 0.11 ≥60 15 22 37 12027557 11781867 23809424 0.12 0.19 0.16 †per 105years. Conclusions This is the first epidemiologic study of TAO in Taiwan using a nationwide, population-based analysis of data from 2002 to 2011. This study showed a trend of decreasing incidence of TAO with time. It is warranted to conduct future clinical studies to further investigate whether or not such findings are associated with a decreasing smoking rate or periodontal disease prevalence in Taiwan. References Olin JW. Thromboangiitis obliterans (Buergers disease). N Engl J Med. 2000;343: 864–869. Sasaki S, Sakuma M, Kunihara T, Yasuda K. Current trends in thromboangiitis obliterans (Buergers disease) in women. Am J Surg. 1999;177: 316–320. Acknowledgement We thank the members of the Bureau of National Health Insurance, Department of Health, and the National Health Research Institutes for the delivery and management, respectively, of the National Health Insurance Research Database. The interpretation and conclusions contained herein do not represent those of Bureau of National Health Insurance, Department of Health, or National Health Research Institutes. Disclosure of Interest None declared