Evaluating the risk of ischemic stroke at a young age in patients with autoimmune inflammatory rheumatic diseases: a population-based cohort study in Taiwan.

Background: Recent studies have demonstrated an increased incidence of ischemic stroke among patients with certain autoimmune inflammatory rheumatic diseases (AIIRDs). However, the associations between young stroke and AIIRDs have not been fully investigated. This study aimed to evaluate the risk of ischemic stroke among young patients with AIIRDs. Methods: The National Health Insurance Research Database in Taiwan was utilized to establish cohorts of patients with AIIRDs diagnosed between 2004 and 2015, who were compared with 1,000,000 control participants. Cox proportional hazards regression models were used to calculate the hazard ratio of ischemic stroke and young ischemic stroke for individual AIIRDs after adjustment for relative risk factors. Results: During the study period, a total of 64,120 patients with AIIRDss and 1,000,000 control patients were identified. The overall mean follow-up time was 5.33 years. There were 223 (0.8%) and 1,923 (0.3%) young ischemic stroke-related hospitalizations among patients with AIIRDs and controls, respectively. The incidence rate of young ischemic stroke was 0.08 in patients with rheumatoid arthritis, 0.08 in patients with Sjögren's syndrome, 0.26 in patients with systemic lupus erythematosus, 0.17 in patients with idiopathic inflammatory myositis, 0.24 in patients with systemic sclerosis, 0.05 in patients with Behçet's disease, and 0.44 in patients with systemic vasculitis, versus 0.05 per 100 person-years in the general population. The adjusted hazard ratios for young ischemic stroke were 1.07 (95% CI 0.70-1.43) for rheumatoid arthritis, 1.39 (95% CI 0.94-2.06) for Sjögren's syndrome, 5.79 (95% CI 4.68-7.17) for systemic lupus erythematosus, 2.07 for idiopathic inflammatory myositis (95% CI 0.98-4.38), 2.79 for systemic sclerosis (95% CI 1.38-5.63), 0.82 for Behçet's disease (95% CI 0.26-2.55), and 4.15 (95% CI 1.96-8.82) for systemic vasculitis. Conclusions: Patients younger than 50 years with systemic lupus erythematosus, systemic sclerosis, or systemic vasculitis have a significantly elevated risk of developing ischemic stroke. Further research is needed to elucidate the pathogenesis of accelerated atherosclerosis in these AIIRDs.

Rituximab, but not other biologics, impairs humoral immunity in patients with rheumatoid arthritis-a study using CoVariant protein arrays.

Objectives: RA is an autoimmune disease characterized by chronic inflammation and joint destruction. Biologics are crucial to achieving treat-to-target goals in patients with RA. The global spread and continuous variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate the monitoring of variant-specific humoral responses post-vaccination. The aim of this study was to investigate how different biologic treatments for vaccinated RA patients might affect their neutralizing antibodies against multiple SARS-CoV-2 variants. Methods: We recruited RA patients who had received three doses of conventional SARS-CoV-2 vaccines and were treated with various biologics, e.g. TNF inhibitor (etanercept), IL-6 inhibitor (tocilizumab), CTLA4-Ig (abatacept) or anti-CD20 (rituximab). Serum samples were used to profile the binding and neutralizing antibodies using our own SARS-CoV-2 variant (CoVariant) protein array, developed previously. Results: Compared with healthy controls, only RA therapy with rituximab showed a reduction in neutralizing antibodies capable of targeting spike proteins in SARS-CoV-2 wild-type and most variants. This reduction was not observed in binding antibodies against SARS-CoV-2 wild-type or its variants. Conclusion: After receiving three doses of SARS-CoV-2 vaccination, RA patients who underwent rituximab treatment generated sufficient antibodies but exhibited lower neutralizing activities against wild-type and multiple variants, including current Omicron. Other biological DMARDs, e.g. TNF inhibitor, IL-6 inhibitor and CTLA4-Ig, did not show obvious inhibition.

Coexistence of Multiple Myositis-Specific Antibodies in Patients with Idiopathic Inflammatory Myopathies.

The mutual exclusivity of myositis-specific antibodies (MSAs) has been reported before, but the coexistence of 2 or more MSAs was still found in a few case reports. This study aims to confirm the existence and prevalence of double MSAs in patients with idiopathic inflammatory myopathy (IIM) and to clarify the clinical features of these patients. One hundred fifty-one patients with IIM diagnosed from 1 July 2018 to 31 July 2022, at National Cheng Kung University Hospital, Taiwan, were enrolled and divided into two groups, patients with ≤1 MSA (n = 128, 84.8%) and those with ≥2 MSAs (n = 23, 15.2%) according to the initial serology results. After being re-examined by ANA-IIF assay, 8 out of 23 patients were confirmed to have ≥2 MSAs. The demographic data and clinical features were presented. The prevalence of double-positive MSAs among IIM was 5.3% in this cohort. The coexistence of two MSAs in an IIM patient does exist but is rare. Patients with two MSAs belonging to two distinct IIM subtypes presented clinical features skewed to one subtype instead of "mixed phenotypes". No apparent difference in clinical severity was found between patients with ≥2 MSAs and ≤1 MSA. Longer follow-ups and more studies are required to characterize the patients of IIM with ≥2 MSAs.

Premature coronary artery disease in patients with immune-mediated inflammatory disease: a population-based study.

BACKGROUND: The associations between premature atherosclerosis and immune-mediated inflammatory diseases (IMIDs) are not fully investigated. To determine whether IMIDs are associated with premature atherosclerosis, we examined the risk of incident coronary artery disease (CAD) in men less than 45 years old and women less than 50 years old with various forms of IMIDs compared with general population. METHODS: A population-based cohort was established and included patients with IMID, who were followed until the development of CAD, withdrawal from the insurance system, death, or 31 December 2016, whichever point came first. Patients with IMID included rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (SjS), idiopathic inflammatory myositis, systemic sclerosis (SSc), Behcet's disease (BD), and systemic vasculitis (SV). The comparison group was 1 000 000 beneficiaries sampled at random from the whole population as matched control participants. The Kaplan-Meier method was used to compare the cumulative incidences of CAD in patients with and without IMID. RESULTS: Among 58 862 patients with IMID, 2139 (3.6%) developed CAD and 346 (1.3%) developed premature CAD. Relative to the comparison cohorts, the adjusted HRs for premature CAD were 1.43 (95% CI 1.09 to 1.86) for primary SjS, 2.85 (95% CI 2.63 to 3.43) for SLE, 3.18 (95% CI 1.99 to 5.09) for SSc and 2.27 (95% CI 1.01 to 5.07) for SV. CONCLUSIONS: Primary Sjogren's syndrome, SLE, SSc and SV are associated with an increased risk of premature CAD. Our findings will support essential efforts to improve awareness of IMID impacting young adults.

Consensus recommendations on managing the selected comorbidities including cardiovascular disease, osteoporosis, and interstitial lung disease in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA)-related comorbidities, including cardiovascular disease (CVD), osteoporosis (OP), and interstitial lung disease (ILD), are sub-optimally managed. RA-related comorbidities affect disease control and lead to impairment in quality of life. We aimed to develop consensus recommendations for managing RA-related comorbidities. METHODS: The consensus statements were formulated based on emerging evidence during a face-to-face meeting of Taiwan rheumatology experts and modified through three-round Delphi exercises. The quality of evidence and strength of recommendation of each statement were graded after a literature review, followed by voting for agreement. Through a review of English-language literature, we focused on the existing evidence of management of RA-related comorbidities. RESULTS: Based on experts' consensus, eleven recommendations were developed. CVD risk should be assessed in patients at RA diagnosis, once every 5 years, and at changes in DMARDs therapy. Considering the detrimental effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids on CVD risks, we recommend using the lowest possible dose of corticosteroids and prescribing NSAIDs cautiously. The OP/fragility fracture risk assessment includes dual-energy X-ray absorptiometry and fracture risk assessment (FRAX) in RA. The FRAX-based approach with intervention threshold is a useful strategy for managing OP. RA-ILD assessment includes risk factors, pulmonary function tests, HRCT imaging and a multidisciplinary decision approach to determine RA-ILD severity. A treat-to-target strategy would limit RA-related comorbidities. CONCLUSIONS: These consensus statements emphasize that adequate control of disease activity and the risk factors are needed for managing RA-related comorbidities, and may provide useful recommendations for rheumatologists on managing RA-related comorbidities.

Improvement of Functioning and Health With Ixekizumab in the Treatment of Active Nonradiographic Axial Spondyloarthritis in a 52-Week, Randomized, Controlled Trial.

OBJECTIVE: To evaluate the effect of ixekizumab on self-reported functioning and health in patients with active nonradiographic axial spondyloarthritis (SpA). METHODS: COAST-X was a randomized, controlled trial conducted in patients with nonradiographic axial SpA over 52 weeks. Participants were randomized at a ratio of 1:1:1 to receive 80 mg of ixekizumab subcutaneously every 4 weeks or 2 weeks or placebo for 52 weeks. Self-reported functioning and health end points included the Medical Outcomes Study Short Form 36 (SF-36) health survey, Assessment of Spondyloarthritis International Society (ASAS) health index, and European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) health-utility descriptive system. RESULTS: Compared to placebo, ixekizumab treatment resulted in improvement of SF-36 physical component summary scores from baseline, with a score of 4.7 improving to 8.9 with ixekizumab therapy every 4 weeks (P < 0.05) and a score of 9.3 with ixekizumab therapy every 2 weeks (P < 0.01); the greatest improvements were observed in the domains of physical functioning, role-physical, and bodily pain at weeks 16 and 52. A higher proportion of patients receiving ixekizumab therapy every 2 weeks reported ≥3 improvements based on the ASAS health index from baseline to weeks 16 and 52 (P < 0.05). Significantly more patients receiving ixekizumab every 4 weeks reported improvements in "good health status" on the ASAS health index (ASAS score of ≤5) at weeks 16 and 52 (P < 0.05). Patients receiving ixekizumab reported improvements on the EQ-5D-5L compared to those who received placebo at week 16 (0.11 versus 0.17 for patients receiving treatment every 4 weeks and 0.19 for patients receiving treatment every 2 weeks; P < 0.05), which remained consistent at week 52. There were no clinical meaningful differences in responses based on the ixekizumab dosing regimen for patients who received ixekizumab therapy every 2 weeks or every 4 weeks. CONCLUSION: In patients with nonradiographic axial SpA, therapy with ixekizumab was superior to placebo in the improvement of self-reported functioning and health at weeks 16 and 52.

Exploring the Quality of Communication Between Patients with Psoriatic Arthritis and Physicians: Results of a Global Online Survey.

INTRODUCTION: Effective communication between patients with psoriatic arthritis (PsA) and their physicians is important for optimizing treatment outcomes. We assessed the quality of patient-physician communication in terms of awareness and impact of PsA symptoms, their levels of satisfaction, and their perceptions of communications. METHODS: A global online survey was conducted by The Harris Poll in adult patients with PsA and physicians managing patients with PsA in eight countries. Participating physicians were either rheumatologists or dermatologists seeing ≥ 10 and ≥ 5 patients with PsA per month, respectively. Patient and physician groups were unmatched. Patient-physician communication was assessed with 35-60 questions regarding discussion topics during consultations, levels of satisfaction with communication, and specific communication issues. RESULTS: A total of 1286 patients with PsA (983 and 303 whose primary treating physician was a rheumatologist or dermatologist, respectively) and 1553 physicians (795 rheumatologists and 758 dermatologists) completed the survey. Regardless of whether they were primarily treated by a rheumatologist or dermatologist, most patients reported a social (84% and 81%, respectively) or work (81% and 80%, respectively) impact of PsA, and a major/moderate negative impact on their physical activity levels (79% and 74%, respectively) or emotional/mental wellbeing (69% and 68%, respectively). Physician responses were generally consistent with this; however, physicians often appeared to under-recognize the extent to which PsA affects patients. Most (≥ 85%) patients and physicians were very/somewhat satisfied with their patient-physician communication, and most (≥ 86%) patients were comfortable raising their concerns/fears with their physician. However, > 40% of patients were identified as being at risk of suboptimal communication. These patients were significantly less likely to report their PsA symptoms even when asked, were less comfortable discussing the impacts of PsA with their physician, and were more likely to experience major/moderate impacts of PsA on their health-related quality of life (HRQoL). CONCLUSIONS: Physicians often underestimate the impacts of PsA, compared with patients, and some patients may be at risk of suboptimal communication with their attending physician, which may worsen the HRQoL impacts of PsA. These findings highlight a need for ways to improve communication between patients with PsA and their healthcare providers.

Psoriatic arthritis (PsA) is a disease that can cause swollen and painful joints, as well as skin psoriasis. To effectively treat PsA, it is important that doctors and patients communicate well. We used a survey to ask patients with PsA and doctors from around the world about their communications about PsA. We also asked how PsA affects patients' quality of life. In total, 1286 patients and 1553 doctors took the survey. Most patients said that PsA affected their social and work lives. Similarly, PsA had a negative impact on physical activity and on emotional and/or mental wellbeing in most patients who answered the survey. Doctors answered similarly, but they were generally less likely to recognize how severely PsA can impact patients, compared with patients themselves. Most patients and doctors were happy with their patient­doctor communication, and most patients felt comfortable talking about their worries and/or fears with their doctor. However, some patients (about four out of 10) felt that communication with their doctors was not good; these patients were less likely/comfortable to talk about their PsA symptoms and the impacts of PsA with their doctor. PsA was also more likely to negatively impact these patients' quality of life. This survey shows that it is important to find ways to improve communication between patients with PsA and their doctors.

Association between 9-month isoniazid prophylaxis of latent tuberculosis and severe hepatitis in patients treated with TNF inhibitors.

To investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan's National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1-28, 29-56, 57-84, 85-168, 169-252, and 253-280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients' baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57-16.55), especially 57-84 days (IRR: 17.29, 95% CI: 3.11-96.25) and 85-168 days (IRR:10.55, 95% CI: 1.90-58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57-168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.

Risk of Heart Failure in Rheumatoid Arthritis Patients Treated with Tumor Necrosis Factor-α Inhibitors.

This is a retrospective cohort study by analyzing a multi-institutional electronic medical records database covering 1.3 million individuals (6% of Taiwan's population) to compare the risk of heart failure (HF) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor-α (TNF-α) inhibitors or conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). We included patients with RA aged 20 years and older who had treatment failure with at least 2 different csDMARD regimens and newly switched to another csDMARD regimen or TNFis from 2009 to 2019. We followed patients from initiation of the new therapies to the occurrence of hospitalization for heart failure (hHF), death, to the last clinical visit or December 31, 2020. We performed multivariable Cox proportional hazard models to compare TNF-α inhibitors and csDMARD groups for the risk of hHF, with adjustment for patients' characteristics. A total of 1,278 TNF-α inhibitors and 1,932 csDMARDs treated patients were identified, with 78% being women and having an average age of 55 (SD 13.28) years. The incidence rates of hHF for the TNF-α inhibitors and csDMARD groups were 3.66 and 4.72 per 1,000 person-years, respectively (adjusted hazard ratio (aHR) 0.59; 95% confidence interval (CI) 0.35-0.97), and the results remained consistent in patients both with an HF history (aHR 0.66; 95% CI 0.03-14.46) and without (aHR 0.49; 95% CI, 0.27-0.89). The findings suggest that those who switched to TNF-α inhibitors had a reduced risk of hHF, compared with those who switched to another csDMARD regimen.

Diagnostic Delay in Patients with Primary Sjögren's Syndrome: A Population-Based Cohort Study in Taiwan.

The diagnosis of primary Sjögren's syndrome (pSS) can be challenging because the cardinal sicca syndromes may be subjective and subclinical. Diagnostic delay is common among patients with pSS. The aim of this study was to assess the time of lag between the onset of sicca symptoms and a subsequent diagnosis of pSS. We used population-based data from Taiwan's National Health Insurance (NHI) claims directory spanning up to 6 years between 2006 and 2011. All NHI-covered patients receiving a first-time approved catastrophic illness certificate (CIC) for pSS in 2011 were included; their sicca symptoms and utilization of medical resources were then traced retrospectively over five years to 2006. The time of lag was identified by observing the onset of sicca symptoms, a diagnosis of Sjögren's syndrome, and the related claim for CIC. A total of 1970 pSS patients were included in this study. The median time of lag between the onset of sicca symptoms and pSS diagnosis was 115 weeks (interquartile range [IQR] 27-205), and between pSS diagnosis and approval of CIC, was 6 (IQR 2-37) weeks. During the time of lag between sicca symptoms, diagnosis, and approval of a CIC for pSS, the median numbers of outpatient visits were 3 (IQR 1-8) and 3 (IQR 2-7), respectively. These numbers were higher in female and elderly groups. Patients experience a significant diagnostic delay of pSS and in the initiation of regular follow-up care. Targeted guardian programs or public health interventions are required to inform symptom interpretation and reduce delays.

The significance of myositis autoantibodies in idiopathic inflammatory myopathy concomitant with interstitial lung disease.

AIM: This study identified factors associated with interstitial lung disease (ILD) in patients with idiopathic inflammatory myopathy (IIM) based on the latest classification and recent advances in autoantibody serology. METHODS: We retrospectively analyzed data of 173 patients who underwent complete myositis autoantibody serology examination in a medical center in Taiwan from July 2018 to February 2020. After exclusion of patients who did not receive a final diagnosis of IIM, clinical features, serology data, concomitant diseases, treatment, presence of respiratory failure, and mortality rate of the remaining 97 patients were analyzed. RESULTS: Of IIM patients in our cohort, 47.4% had ILD. ILD was significantly associated with subtypes of IIM, older age of onset, presence of mechanic's hand, and presence of anti-Jo-1 and anti-Ro52 antibodies. Among five IIM subtypes, overlap myositis (OM) and dermatomyositis (DM) were significantly associated with a higher prevalence rate of ILD (67.5% in OM and 53.3% in DM). Among patients with OM, the presence of anti-Jo-1 (100%), anti-PL-7 (100%), and anti-EJ antibodies (77.8%) was most significantly associated with ILD. CONCLUSION: The latest classification of IIM, older age of onset, presence of mechanic's hand, and presence of anti-Jo-1 and anti-Ro52 antibodies were significantly associated with ILD. Among five IIM subtypes, OM and DM had higher prevalence rate of ILD. Among OM patients, the presence of anti-Jo-1, anti-EJ, and anti-PL-7 antibodies was significantly associated with ILD. The study results may help physicians to timely screen and monitor pulmonary function in high-risk groups.

Increased risk of coronary heart disease among patients with idiopathic inflammatory myositis: a nationwide population study in Taiwan.

OBJECTIVE: To evaluate the risk of incident coronary heart disease (CHD) among patients with DM and PM in a general population context. METHODS: We conducted a retrospective cohort study using the Taiwan National Health Insurance Research Database containing records covering the years from 2000 to 2010. DM and PM were confined for the purposes of this study to those aged ⩾18 years who were eligible for the Taiwan catastrophic illness certificate. The diagnoses, CHD outcomes and cardiovascular risk factors were identified from electronic claims data. We conducted two cohort analyses: CHD and DM, and CHD and PM, excluding for each analysis individuals with CHD already identified at baseline. Data for the comparison group was obtained from the Longitudinal Health Insurance database, comprising 1 million persons randomly sampled from the total beneficiaries during 2000. We estimated hazard ratios comparing myositis with comparison cohorts, adjusting for potential cardiovascular risk factors. RESULTS: A total of 1145 patients with idiopathic myositis were identified, along with 732 723 control patients aged ⩾18 years. The incidence rates of CHD were 15.1 in DM and 30.1 in PM per 1000 person-years, vs 8.4 and 10.5 per 1000 person-years in the comparison cohort. The adjusted hazard ratios for CHD in patients with idiopathic myositis were 2.21 (95% CI 1.64, 2.99) for DM and 3.73 (95% CI 2.83, 4.90) for PM. CONCLUSION: Results of this general population-based cohort study suggest that DM and PM are associated with an increased risk of CHD.

In Situ Monitoring of Chemical Reactions at a Solid-Water Interface by Femtosecond Acoustics.

Chemical reactions at a solid-liquid interface are of fundamental importance. Interfacial chemical reactions occur not only at the very interface but also in the subsurface area, while existing monitoring techniques either provide limited spatial resolution or are applicable only for the outmost atomic layer. Here, with the aid of the time-domain analysis with femtosecond acoustics, we demonstrate a subatomic-level-resolution technique to longitudinally monitor chemical reactions at solid-water interfaces, capable of in situ monitoring even the subsurface area under atmospheric conditions. Our work was proven by monitoring the already-known anode oxidation process occurring during photoelectrochemical water splitting. Furthermore, whenever the oxide layer thickness equals an integer  number of the effective atomic layer thickness, the measured acoustic echo will show higher signal-to-noise ratios with reduced speckle noise, indicating the quantum-like behavior of this coherent-phonon-based technique.

Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study.

OBJECTIVE: To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. DESIGN: National prospective cohort study. SETTING: 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. PARTICIPANTS: 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants' peripheral blood was used to assess the presence of HLA-B*58:01. MAIN OUTCOME MEASURES: Incidence of allopurinol induced SCARs with and without screening. RESULTS: Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). CONCLUSIONS: Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence of allopurinol induced SCARs in Taiwanese medical centres.

Mining disease risk patterns from nationwide clinical databases for the assessment of early rheumatoid arthritis risk.

Rheumatoid arthritis (RA) is a chronic autoimmune rheumatic disease that can cause painful swelling in the joint lining, morning stiffness, and joint deformation/destruction. These symptoms decrease both quality of life and life expectancy. However, if RA can be diagnosed in the early stages, it can be controlled with pharmacotherapy. Although many studies have examined the possibility of early assessment and diagnosis, few have considered the relationship between significant risk factors and the early assessment of RA. In this paper, we present a novel framework for early RA assessment that utilizes data preprocessing, risk pattern mining, validation, and analysis. Under our proposed framework, two risk patterns can be discovered. Type I refers to well-known risk patterns that have been identified by existing studies, whereas Type II denotes unknown relationship risk patterns that have rarely or never been reported in the literature. These Type II patterns are very valuable in supporting novel hypotheses in clinical trials of RA, and constitute the main contribution of this work. To ensure the robustness of our experimental evaluation, we use a nationwide clinical database containing information on 1,314 RA-diagnosed patients over a 12-year follow-up period (1997-2008) and 965,279 non-RA patients. Our proposed framework is employed on this large-scale population-based dataset, and is shown to effectively discover rich RA risk patterns. These patterns may assist physicians in patient assessment, and enhance opportunities for early detection of RA. The proposed framework is broadly applicable to the mining of risk patterns for major disease assessments. This enables the identification of early risk patterns that are significantly associated with a target disease.

Pneumocystis jirovecii pneumonia in systemic lupus erythematosus from southern Taiwan.

BACKGROUND: Opportunistic infection has been documented in systemic lupus erythematosus with special attention paid to Pneumocystis jirovecii because of the significant morbidity and high mortality. OBJECTIVES: The limited large-scale investigations covering P. jirovecii pneumonia (PCP) in systemic lupus erythematosus following biologics or immunosuppressants therapy prompted us to perform this study in southern Taiwan. METHODS: A retrospective study was completed in 858 hospitalized lupus patients from January 2000 to December 2011. The definite diagnosis of PCP was made by the laboratory detection of Pneumocystis organisms together with consistent clinical and radiological manifestations of PCP. Positive polymerase chain reaction results of sputum samples were not regarded as infection in this study, unless P. jirovecii was the sole pathogen found and pulmonary manifestations resolved following antibiotics for PCP treatment alone. RESULTS: The laboratory identification of Pneumocystis organisms depended on lung biopsy in 2 cases and bronchoalveolar lavage in 3 patients. Five cases, 2 women and 3 men aged 30 to 50 years (41.8 ± 8.8 years), were identified with a 0.6% incidence. None received chemoprophylactics against P. jirovecii infection. All had lupus nephritis and lymphopenia with low CD4 T-cell counts. Prior usages of higher daily prednisolone dosages and concomitant biologics or immunosuppressants were observed in all patients. Pneumocystis jirovecii pneumonia contributed to a high mortality rate (60%). CONCLUSIONS: We report the rare occurrence but high mortality of PCP infection in this study. A consensus guideline addressing prophylactic antibiotics against Pneumocystis organisms in highest-risk lupus patients on biologics or immunosuppressants could be helpful in guiding their management.

Incidence of cancer in a nationwide population cohort of 7852 patients with primary Sjogren's syndrome in Taiwan.

OBJECTIVES: Patients with primary Sjögren's syndrome (pSS) are at a higher risk of developing non-Hodgkin's lymphoma (NHL). However, little is known with regard to the risk of developing cancers other than NHL. The authors aimed in this study to compare the incidence of cancer in various sites among patients with pSS with the general population of Taiwan. METHODS: The authors used National Health Insurance claims data to establish a nationwide population cohort of 7852 patients with pSS from 2000 to 2008 who did not have cancer prior to diagnosis of pSS. Incidence and standardised incidence ratios (SIRs) for cancer in various sites were calculated. RESULTS: Among patients with pSS, 277 (2.9%) developed cancer. The SIR for cancer was 1.04 (95% CI 0.91 to 1.18) among patients of all ages with pSS and was 2.19 (95% CI 1.43 to 3.21) for patients aged 25-44 years. Female patients with pSS had a higher risk of NHL (SIR 7.1, 95% CI 4.3 to 10.3), multiple myeloma (SIR 6.1, 95% CI 2.0 to 14.2) and thyroid gland cancer (SIR 2.6, 95% CI 1.4 to 4.3) and a lower risk of colon cancer (SIR 0.22, 95% CI 0.05 to 0.65). In contrast, male patients with pSS were not at a higher risk of developing cancer in particular sites. CONCLUSION: Patients with pSS, overall, did not have higher risk of cancer, and only patients aged 25-44 years were at an increased risk of cancer compared with their counterparts in the general population. Cancer screening for patients with pSS, especially female patients, should focus on NHL and multiple myeloma and thyroid gland cancer.

Incidence and mortality of treated primary Sjogren's syndrome in Taiwan: a population-based study.

OBJECTIVE: To estimate the incidence and mortality of treated primary Sjögren's syndrome (pSS) by sex and age group in Taiwan. METHODS: We used claims data of the Bureau of National Health Insurance (NHI) of Taiwan from 2005 to 2007 for analysis. According to the NHI, pSS is classified as one of the financially catastrophic illnesses and patients with pSS could be exempted from copayment of all medical costs. To obtain a catastrophic illness certificate (CIC) for pSS, patients are required to meet the criteria of the American-European Consensus Group for pSS, and are reviewed by a committee. Patients approved for receipt of a CIC for pSS for the first time were defined as incident cases of treated pSS. RESULTS: A total of 3352 incident cases occurred between 2005 and 2007. The estimated mean annual incidence was 6.0 per 100,000 inhabitants (95% CI 5.8-6.2) for both sexes, 11.0 (95% CI 10.6-11.4) for women and 1.1 (95% CI 1.0-1.2) for men, with a female/male ratio of 9.9 (95% CI 8.8-11.1). Incidence increased with age, peaking at age 55-64 years in women and 65-74 years in men. The mortality rate was 33.4 per 1000 case person-years for men and 11.4 for women, with a male/female rate ratio of 2.9 (95% CI 1.7-5.3). CONCLUSION: The incidence of treated pSS in women is 10 times that in men. Nevertheless, pSS mortality in men is 3 times that in women.

The efficacy of low-dose mycophenolate mofetil for treatment of lupus nephritis in Taiwanese patients with systemic lupus erythematosus.

Mycophenolate mofetil (MMF) has recently been introduced as an immunosuppressive agent for the treatment of glomerulonephritis with systemic lupus erythematosus (SLE) and the data have been encouraging. However, response to MMF treatment appears to differ ethnically. Therefore, we determined efficacy and safety of low-dose MMF for Taiwanese patients with lupus nephritis. We studied 36 lupus nephritis patients who were treated with MMF. The dose started at 0.5 g/day and we collected the data from patients who received up to 1 g/day MMF. Outcome measures were 24 h for proteinuria, serum creatinine, C3/C4 levels, and anti-dsDNA titers collected at the baseline and at 3-month treatment intervals. Daily urinary protein significantly decreased from 6.15 +/- 4.28 g to 2.69 +/- 2.36 g at the last visit (P < 0.01) in spite of the significant absence of changes in serum creatinine levels. The response rate was 65.7% including five (14.3%) cases of complete remission and 18 (51.4%) cases of partial remission. The concomitant oral prednisolone dose decreased significantly from 20.07 +/- 11.78 mg/day to 13.93 +/- 6.79 mg/day at 6 months (P < 0.01). The level of C3 increased significantly from 59.46 +/- 32.73 to 71.99 +/- 25.81 (P < 0.01) and the anti-dsDNA antibody titer decreased from 161.71 +/- 221.42 to 46.57 +/- 117.47 (P < 0.01). No severe adverse effects were observed in the study. Low-dose MMF (0.5 to 1 g/day) combined with glucocorticoids appears to be a safe and effective therapy for lupus nephritis in Taiwanese patients. Our results suggest that lupus nephritis in Oriental patients might respond to lower doses of MMF than Caucasians.