Risk of uveitis in autoimmune diseases patients treated with hydroxychloroquine: A population-based retrospective cohort study.

OBJECTIVE: Uveitis is a common manifestation of various autoimmune diseases and can lead to severe visual impairment. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used to treat autoimmune diseases. The aim of this study was to investigate the association between HCQ use and the incidence of uveitis in patients with autoimmune diseases, as well as to identify potential risk factors for the development of uveitis in this study. METHODS: We conducted a population-based cohort study using a nationwide database to investigate the incidence of uveitis in patients with autoimmune diseases who received HCQ treatment. We selected non-HCQ comparison cohort at a 1:1 ratio by propensity score matching on age, sex, index date, urbanization, income, comorbidities, and medications. The data were analyzed using Cox proportional hazards models, and propensity score matching (PSM) was used to reduce selection bias. RESULTS: Our study included 15 822 patients with autoimmune diseases. After 1:1 PSM, there were 4555 individuals in both the HCQ group (n = 4555) and the non-HCQ group (n = 4555). The multiple Cox proportional hazard regression analysis was used for the estimation of adjusted hazard ratios on uveitis. After PSM, the adjusted hazard ratio for the HCQ group was 0.74 (95% CI = 0.58-0.95). These findings suggest that HCQ may play a protective role in reducing the risk of uveitis in patients with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus groups. The Kaplan-Meier survival curves also showed a significantly lower incidence of uveitis in the HCQ group (log-rank = 0.0229) after PSM. CONCLUSION: HCQ use is associated with a lower incidence of uveitis in patients with autoimmune diseases. Further studies are needed to confirm this association and to investigate the underlying mechanisms.

Risk of new-onset glaucoma in patients with systemic lupus erythematosus: A nationwide, population-based cohort study.

To explore the relationship of systemic lupus erythematosus (SLE) and subsequent glaucoma incidence. Patients with SLE were defined as those newly diagnosed by International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 710.0 in at least 3 outpatient visits or 1 hospitalization during 2000-2012 by using the National Health Insurance Research Database. We selected a non-SLE comparison cohort at a 1:1 ratio by propensity score matching on age, gender, index date, comorbidities and medications. We identified outcome as the incident glaucoma in patients with SLE. Multivariate Cox regression analysis was used to calculate the adjusted hazard ratio (aHR) in 2 groups. Kaplan- Meier analysis was performed to estimate the cumulative incidence rate between both groups. There were 1743 patients who were included in the SLE group and non-SLE group. The aHR of glaucoma was 1.56 (95% CI = 1.03-2.36) in the SLE group, compared to non-SLE controls. Subgroup analysis showed that SLE patients present greater risk of glaucoma, especially in males (aHR = 3.76; 95% CI, 1.5-9.42), and the P for interaction between gender and risk of glaucoma was 0.026. This cohort study showed that patients with SLE have 1.56-fold risk of glaucoma development. Gender acted as an effect modifier between SLE and the risk of new-onset glaucoma.

The Risk of Major Adverse Cardiovascular Events in Ankylosing Spondylitis Patients With a History of Acute Anterior Uveitis: A Nationwide, Population Based Cohort Study.

Background: To investigate the association between a history of acute anterior uveitis (AAU) and the risk of major adverse cardiovascular events (MACE) among patients with ankylosing spondylitis (AS). Methods: We identified 38,691 newly diagnosed AS patients between 2003 and 2013 from the Taiwan National Health Insurance Research Database. The exposure group was defined as people with uveitis diagnosis by ophthalmologist before AS diagnosis date. The incidence of MACE in patients with AS according to the International Classification of Diseases, Ninth Revision. We randomly selected a comparison group without a history of AAU at a 1:4 ratio matched by age, sex, and index year in relation to the risk of developing MACE. We used cox proportional hazard regression model to compare the risk of MACE between groups, shown as adjusted hazard ratios (aHRs) with 95% confidence intervals (CI). Further subgroup analysis and sensitivity tests were also performed. Results: There were 3,544 patients in the AAU group and 14,176 patients in the non-AAU group. The aHR of MACE for the AAU group was 0.79 (95% CI = 0.57-1.10) at a 1:4 ratio for age, sex and index year. Sensitivity analyses using various adjustment variables showed consistent results. Cox proportional hazard regression model demonstrated that use of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of MACE in this cohort (HR = 3.44; 95% CI = 2.25-5.25). Conclusion: This cohort study showed that subjects with AAU was not associated with the risk of MACE among AS patients, compared to non-AAU controls.

Association Between Air Pollution and the Risk of Uveitis: A Nationwide, Population-Based Cohort Study.

Previous studies have revealed an association between ocular surface disorders and air pollution, few studies have focused on the risk of uveitis. We aimed to investigate whether air pollution increases the risk of uveitis. We used the Taiwan Longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality Monitoring Database (TAQMD) to conduct a retrospective cohort study. Air pollutant concentrations, including those of carbon dioxide (CO2), were grouped into four levels according to quartiles. The outcome was the incidence of uveitis, as defined in the International Classification of Diseases, Ninth Revision. We used univariable and multivariable Cox proportional hazard regression models to calculate the adjusted hazard ratios (aHRs) and determine the potential risk factors of uveitis. Overall, 175,489 subjects were linked to their nearby air quality monitoring stations. We found that for carbon monoxide, the aHRs of uveitis risk for the Q3 and Q4 levels were 1.41 (95% confidence interval (CI) = 1.23-1.61) and 2.19 (95% CI = 1.93-2.47), respectively, in comparison with those for the Q1 level. For nitric oxide, the aHRs for the Q3 and Q4 levels were 1.46 (95% CI = 1.27-1.67) and 2.05 (95% CI = 1.81-2.32), respectively. For nitrogen oxide (NOx), the aHRs for the Q2, Q3, and Q4 levels were 1.27 (95% CI = 1.11-1.44), 1.34 (95% CI = 1.16-1.53), and 1.85 (95% CI = 1.63-2.09), respectively. For total hydrocarbon (THC), the aHRs for the Q2, Q3, and Q4 levels were 1.42 (95% CI = 1.15-1.75), 3.80 (95% CI = 3.16-4.57), and 5.02 (95% CI = 4.19-6.02), respectively. For methane (CH4), the aHRs for the Q3 and Q4 levels were 1.94 (95% CI = 1.60-2.34) and 7.14 (95% CI = 6.01-8.48), respectively. In conclusion, air pollution was significantly associated with incidental uveitis, especially at high THC and CH4 levels. Furthermore, the uveitis risk appeared to increase with increasing NOx and THC levels.

The prevalence and incidence of systemic lupus erythematosus in Taiwan: a nationwide population-based study.

To estimate the prevalence and incidence rate of systemic lupus erythematosus (SLE) in Taiwan by using a population-based longitudinal database from 2001 to 2011. We conducted a longitudinal Health Insurance Database (LHID) containing 1,000,000 beneficiaries' records for calculation of prevalence and incidence rate of SLE from 2001-2011. The overall prevalence of SLE in Taiwan in 2011 is 8.11 per 10,000 people with 14.3 per 10,000 people in female and 1.62 per 10,000 people in male. The overall incidence rate of SLE is 0.74-1 per 10,000 person-years with 1.09-1.76 per 10,000 person-years in female and 0.12-0.25 per 10,000 person-years in male. The highest prevalence rate was observed at 40-49 age group in females. There were no significant differences in the overall prevalence among the urban, suburban and rural area in Taiwan while the relative risk is higher in male population living in rural area (RR 1.36, 95% C.I. 1.03-1.79, p = 0.0303). The highest income group has a lower relative risk for the prevalence of SLE (RR 0.83, 95% C.I. 0.71-0.97, p = 0.0197). The incidence rate of SLE in male in the rural area is also higher than the urban area (RR 2.34, 95% C.I. 1.3-4.22, p = 0.0046). Our study covers the longest period among the nation-wide population studies of SLE in Taiwan. The prevalence was increasing especially in the elderly.

Patients With Rheumatoid Arthritis Increased Risk of Developing Osteoarthritis: A Nationwide Population-Based Cohort Study in Taiwan.

Objective: To investigate the risk of developing OA in patients diagnosed with RA. Methods: In this study, we presented gender, age, urbanization, occupation and, comorbidities in a RA cohort and a non-RA cohort based on number and percentage. We investigated the OA risk in patients with RA. We conducted a retrospective cohort study with a 13-year longitudinal follow-up in Taiwan. Patients who received RA diagnoses between 2000 and 2012 were enrolled in the study cohort. The non-RA cohort were 1:1 propensity score matched with the RA cohort by age, gender, index year, urbanization, occupation, and comorbidities. The hazard ratios (HRs) and adjusted HRs (aHRs) were estimated after confounders were adjusted. Sensitivity analysis utilizing the Longitudinal Health Insurance Database (LHID) was conducted. Results: We totally enrolled 63,626 cases in RA patients (study cohort) and matched controls. In the RA cohort, the crude HR for OA was 2.86 (95% confidence interval (CI), 2.63-3.11, p < 0.001), and the aHR was 2.75 (95% CI, 2.52-2.99, p < 0.001). (The study demonstrated that patients with RA had a higher risk for developing OA compared with the non-RA controls. Conclusion: Developing effective OA prevention strategies are necessary in patients with RA. This finding may be extended to evaluate the risk of OA among other kinds of inflammatory autoimmune diseases. Identifying the key pathogenesis mechanisms are necessary in the future study.

Liraglutide protects against glucolipotoxicity-induced RIN-m5F ß-cell apoptosis through restoration of PDX1 expression.

Prolonged exposure to high levels of glucose and fatty acid (FFA) can induce tissue damage commonly referred to as glucolipotoxicity and is particularly harmful to pancreatic ß-cells. Glucolipotoxicity-mediated ß-cell failure is a critical causal factor in the late stages of diabetes, which suggests that mechanisms that prevent or reverse ß-cell death may play a critical role in the treatment of the disease. Transcription factor PDX1 was recently reported to play a key role in maintaining ß-cell function and survival, and glucolipotoxicity can activate mammalian sterile 20-like kinase 1 (Mst1), which, in turn, stimulates PDX1 degradation and causes dysfunction and apoptosis of ß-cells. Interestingly, previous research has demonstrated that increased glucagon-like peptide-1 (GLP-1) signalling effectively protects ß cells from glucolipotoxicity-induced apoptosis. Unfortunately, few studies have examined the related mechanism in detail, especially the role in Mst1 and PDX1 regulation. In the present study, we investigate the toxic effect of high glucose and FFA levels on rat pancreatic RINm5F ß-cells and demonstrate that the GLP-1 analogue liraglutide restores the expression of PDX1 by inactivating Mst1, thus ameliorating ß-cell impairments. In addition, liraglutide also upregulates mitophagy, which may help restore mitochondrial function and protect ß-cells from oxidative stress damage. Our study suggests that liraglutide may serve as a potential agent for developing new therapies to reduce glucolipotoxicity.