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This study aims to provide an investigation of the containment and mitigation strategies encompassing the entirety of the pandemic in Taiwan. This descriptive, observational study used COVID-19 data from Taiwan, Japan, and South Korea, and analysed news releases from the Taiwanese health authority. Statistics provided evidence of outbreak severity through infection and mortality rates, while qualitative results from the document review offered insights on the actions taken by the government chronologically from 2 February 2020 to 31 December 2022. All three countries experienced significant infection peaks in 2022. Taiwan had two distinct peaks, one in late May and another in October. South Korea had a single, high peak in late March, while Japan experienced multiple smaller waves, the biggest wave in August. Similarly, weekly mortality rates peaked in 2022 for all three countries after a surge in their infected cases, with Taiwan (5.15/100 000) and South Korea (4.69/100 000) having higher rates than Japan (1.65/100 000). Results from qualitative analysis showed that Taiwan's early containment measures might have delayed the epidemic curve, allowing time for better preparation and proactive responses. However, the lack of a clear transition plan and the vulnerability of the elderly population contributed to higher mortality and infection rates. Despite ongoing challenges, Taiwan avoided nationwide lockdowns and relied on targeted restrictions to control transmission of the virus. Results of this article offer the narratives, reflections, and experiences from the case of Taiwan which may potentially present promising opportunities for impact in other settings and for future pandemics., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Background: The prevalence of Pneumocystis jirovecii (PJ) pneumonia among rheumatic patients is rising. PJ colonization serves as a reservoir for transmission and precedes the development of PJ pneumonia. We aim to clarify the association of PJ colonization in patients of rheumatoid arthritis (RA) treated with biologics or Janus kinase inhibitors (JAKi)., Methods: A prospective cohort study was performed from March 2021 to July 2022 in the rheumatology outpatient department of National Cheng Kung University Hospital. We obtained oral-wash samples from asymptomatic RA patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and JAKi. A real-time quantitative polymerase chain reaction assay focusing on the mitochondrial large subunit ribosomal ribonucleic acid gene of PJ was applied to detect colonization., Results: One hundred and ten RA patients were enrolled. Adjusted odds ratios (ORs) of PJ colonization were 6.40 (95% CI 1.34-30.57, p-value =0.02) in patients receiving bDMARDs or JAKi. Specifically, in patients treated with bDMARDs the adjusted OR was 8.08 (95% CI 1.57-41.51, p-value=0.012), and a trend toward developing PJ colonization was further identified in patients receiving JAKi (adjusted OR: 4.79, 95% CI 0.89-25.91, p=0.069). Among patients treated with bDMARDs or JAKi, medication duration >3 years and age >60 y/o are risk factors for PJ colonization., Conclusion: RA patients on bDMARDs or JAK inhibitors have an approximately 6-fold higher risk of developing P. jirovecii colonization. Patients treated with bDMARDs had an 8-fold higher risk of P. jirovecii colonization. Risk factors of PJ colonization are medication duration >3 years and age > 60 y/o., Competing Interests: Declaration of competing interest All authors have no conflict of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Groundwater is one of the important freshwater resources on Earth and is closely related to human activities. As a good biological vector, a more diverse repertory of antibiotic resistance genes in the water environment would have a profound impact on human medical health. Therefore, this study conducted a metagenomic sequencing analysis of water samples from groundwater monitoring points in the middle and lower reaches of the Yangtze River to characterize microbial community composition and antibiotic resistance in the groundwater environment. Our results show that different microbial communities and community composition were the driving factors in the groundwater environment, and a diversity of antibiotic resistance genes in the groundwater environment was detected. The main source of antibiotic resistance gene host was determined by correlation tests and analyses. In this study, metagenomics was used for the first time to comprehensively analyze microbial communities in groundwater systems in the middle and lower reaches of the Yangtze River basin. The data obtained from this study serve as an invaluable resource and represent the basic metagenomic characteristics of groundwater microbial communities in the middle and lower reaches of the Yangtze River basin. These findings will be useful tools and provide a basis for future research on water microbial community and quality, greatly expanding the depth and breadth of our understanding of groundwater.

An N -iodosuccinimide-promoted annulation of alkylidene pyrazolones with enamino esters has been explored to construct a spiropyrazolone moiety through a Michael addition/iodination/intramolecular nucleophilic substitution sequence. When the reaction was performed in acetonitrile at 100 °C, it furnished pyrrolinyl spiropyrazolones exclusively in an anti configuration through N-attacking cyclization. When the reaction was performed in dimethyl sulfoxide at 80 °C in the presence of K 2 HPO 4 , it afforded cyclopentenyl spiropyrazolones exclusively in the syn configuration through C-attacking cyclization. A plausible mechanism has also been proposed.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Huang, Lai, Liao and Weng.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

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., Competing Interests: The authors declare no conflict of interest.

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., (© 2020 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

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., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2021 The Authors. Clinical Pharmacology & Therapeutics © 2021 American Society for Clinical Pharmacology and Therapeutics.)

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., (© 2021. The Author(s).)

Recent improvements in both X-ray detectors and readout speeds have led to a substantial increase in the volume of X-ray fluorescence data being produced at synchrotron facilities. This in turn results in increased challenges associated with processing and fitting such data, both temporally and computationally. Herein an abridging approach is described that both reduces and partially integrates X-ray fluorescence (XRF) data sets to obtain a fivefold total improvement in processing time with negligible decrease in quality of fitting. The approach is demonstrated using linear least-squares matrix inversion on XRF data with strongly overlapping fluorescent peaks. This approach is applicable to any type of linear algebra based fitting algorithm to fit spectra containing overlapping signals wherein the spectra also contain unimportant (non-characteristic) regions which add little (or no) weight to fitted values, e.g. energy regions in XRF spectra that contain little or no peak information.

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., (© 2021. The Author(s).)

The solvent-free reaction of 4-alkylidene pyrazolones with amidines can furnish 4,5'-imidazolinyl spiropyrazolones in good to excellent yields when promoted by N -iodosuccinimide under solvent-free ball-milling conditions, whereas it almost exclusively affords 4,4'-imidazolinyl spiropyrazolones if mediated by N -bromosuccinimide in heated toluene. On the basis of this switchable cyclization strategy, a powerful metal-free method for regioselective and diastereoselective synthesis of structurally diverse 4,5'- and 4,4'-imidazolinyl spiropyrazolones has been successfully developed.

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.

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.

Background: Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory musculoskeletal disease, manifesting as peripheral arthritis, enthesitis, dactylitis, spondylitis, and skin and nail psoriasis. A core set of domains for measuring the impact of PsA has been developed, including pain, patient global assessment, physical function, health-related quality of life (HRQoL), and fatigue. To understand the impact of PsA on health domains from a patient's perspective, a global survey was developed and results reported in the context of the 12-item Psoriatic Arthritis Impact of Disease (PsAID-12) questionnaire., Methods: An online patient-based global survey was conducted by The Harris Poll in Australia, Brazil, Canada, France, Spain, Taiwan, the UK, and the US between November 2, 2017 and March 12, 2018. Eligible patients were ≥ 18 years old with a diagnosis of PsA for > 1 year, had visited a rheumatologist/dermatologist in the past 12 months and reported using ≥ 1 synthetic/biologic disease-modifying antirheumatic drug for PsA. Patients reported on PsA severity and symptoms, and the impact of PsA on HRQoL. After survey completion, responses were aligned with PsAID health domains. Descriptive statistics and chi-square tests were conducted., Results: This analysis included 1286 patients from eight countries. Most patients (97%) reported musculoskeletal symptoms relating to PsA in the past year. Common moderate/major impacts of PsA were on physical activity (78%), ability to perform certain activities (76%), work productivity (62%), and career path (57%). Skin/nail symptoms occurred in 80% of patients. Overall, 69% of patients reported that PsA had a moderate/major impact on emotional/mental wellbeing, 56% on romantic relationships/intimacy, and 44% on relationships with family and friends. Social impacts included emotional distress (58%), social shame or disapproval (32%), and ceased participation in social activities (45%). Over half of all patients experienced unusual fatigue over the past 12 months (52%). The health domains that patients reported as being impacted by PsA aligned with life impact domains of the patient-derived PsAID health domains., Conclusion: These results highlight the impact of PsA on multiple health domains from a patient perspective that should be considered during shared decision-making processes between healthcare providers and patients.

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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.

N-doped graphene (NDG) was investigated for oxygen reduction reaction (ORR) and used as air-electrode catalyst for Zn-air batteries. Electrochemical results revealed a slightly lower kinetic activity but a much larger rate capability for the NDG than commercial 20% Pt/C catalyst. The maximum power density for a Zn-air cell with NDG air cathode reached up to 218 mW cm -2 , which is nearly 1.5 times that of its counterpart with the Pt/C (155 mW cm -2 ). The equivalent diffusion coefficient (D E ) of oxygen from electrolyte solution to the reactive sites of NDG was evaluated as about 1.5 times the liquid-phase diffusion coefficient (D L ) of oxygen within bulk electrolyte solution. Combined with experiments and ab initio calculations, this seems counterintuitive reverse ORR of NDG versus Pt/C can be rationalized by a spontaneous adsorption and fast solid-state diffusion of O 2 on ultralarge graphene surface of NDG to enhance effective ORR on N-doped-catalytic-centers and to achieve high-rate performance for Zn-air batteries.

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., (© Ko et al 2015.)

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.

Background: The purpose of this study was to detect the serum microRNAs (miRNAs) that are differentially expressed in cervical squamous cell carcinoma (SCC) patients and negative controls, with a focus on the miRNA profiles of the patients before and after surgery. The aim of the study is to evaluate the potential of these miRNAs as novel markers for the post-therapeutic monitoring of cervical SCC patients., Results: A total of 765 serum miRNAs from 10 cervical SCC patients before surgery, 10 cervical SCC patients after surgery, and 10 negative controls were profiled using a TaqMan MicroRNA Array. A set of selected differentially expressed miRNAs were further analyzed in the patients at different perioperative periods, including preoperative, 1 week postoperative, and one month postoperative. The results showed that several serum miRNAs were differentially expressed in the cervical SCC patients compared with the negative controls, including miR-646, miR-141* and miR-542-3p. More importantly, we found that levels of specific serum miRNAs were deregulated in the pre- and postoperative stages, and these miRNAs could be useful for post-therapeutic monitoring of disease progression. Finally, we depicted a regulatory network of differentially expressed serum miRNAs, and many possible target genes were predicted in the estrogen-mediated signal pathways, supporting the hypothesis that cervical SCC is a hormone-associated gynecological disease., Conclusions: Our study demonstrated that the circulating miRNAs miR-646, miR-141* and miR-542-3p could potentially serve as non-invasive biomarkers for cervical SCC. The levels of these specific miRNAs might be useful for the post-therapeutic monitoring of disease progression. This is the first report showing that circulating miRNAs could serve as biomarkers for the therapeutic intervention of cervical SCC.

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.

Objective: This work aims to investigate the expression pattern and clinicopathologic significance of centromere protein H (CENP-H) in uterine cervical cancer (UCC)., Methods: The level of CENP-H expression in the paraffin sections of 62 UCC cases was determined by the SP immunohistochemical method, with complete clinicopathologic data in all cases. Statistical analysis was conducted to evaluate the prognostic and diagnostic significance of CENP-H using SPSS13.0 software package., Results: Immunohistochemical assay showed strong CENP-H expression in 61.29% (38/62) of the paraffin-embedded cervical cancer tissues. Statistical analysis revealed a strong correlation between the CENP-H expression and the clinical classification (P=0.038) of the cervical carcinoma. The expression increased with rise of the stages. The analysis of Cox proportional hazards regression model suggested that CENP-H expression (P=0.002) and tumor stage (P=0.001) were independent prognostic markers for the survival of UCC patients. The survival analysis showed that the survival rate was significantly lower in patients with high expression of CENP-H than in those with low expression of CENP-H (P=0.001)., Conclusions: CENP-H is likely to be a valuable marker for carcinogenesis and progression of UCC. It might be used as the important diagnostic and prognostic marker for cervical carcinoma patients, especially for those at early stage.

Objective: Bmi-1, a putative proto-oncogene, is a core member of the polycomb gene family, which is expressed in many human tumors. The p16 protein negatively regulated cell proliferation, whereas CD44v6 is associated with proliferation as an important protein. Additionally, CD44v6 is an important nuclear antigen closely correlated to tumor metastasis. The present study aims to investigate the expression and significance of Bmi-1, p16, and CD44v6 in uterine cervical carcinoma (UCC)., Methods: A total of 62 UCC, 30 cervical neoplasic, and 20 normal cervical mucosal tissues were used in the current study. The expression of Bmi-1, p16, and CD44v6 in these tissues was determined using immunohistochemical assay. The relationships among the expression of these indices, the clinicopathologic features of UCC, and the survival rate of UCC patients were also discussed. The correlation between Bmi-1 protein expression and p16 or CD44v6 protein in UCC was analyzed., Results: The expression of Bmi-1, p16, and CD44v6 was significantly high in cervical carcinoma compared with that in the cervical neoplasia and normal colorectal mucosa (P<0.05). The over-expression of Bmi-1 protein in UCC was apparently related to the distant metastasis (P<0.01) and the tumor, nodes and metastasis-classification, i.e. the TNM staging, World Health Organization (P<0.05). Nevertheless, the positive expression of p16 protein in UCC was not significantly associated with the clinicopathologic features (P>0.05). The Kaplan-Meier survival analysis showed that the over-expression of Bmi-1 significantly decreased the survival rate of UCC patients (P<0.05). A strong correlation indicated that there was statistical significance between the expression of Bmi-1 and CD44V6 proteins in UCC (r=0.419, P=0.001)., Conclusions: The over-expression of Bmi-1 and CD44v6 protein closely correlate to the tumorigenesis, metastasis, and prognosis of UCC. Bmi-1 and CD44v6 may be used to predict the prognosis of cervical carcinoma. Bmi-1 may indirectly regulate the expression of CD44v6 in UCC patients. The positive expression of p16 protein is possibly associated with the tumorigenesis, but not with the metastasis or prognosis of UCC.

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.

As very few large scale publications of invasive fungal infection (IFI) have been reported in lupus patients from individual medical centers, a retrospective study was performed from 1988 to 2009 in southern Taiwan. Demographic characteristics, clinical and laboratory data, and mycological examinations were analyzed. Twenty cases with IFI were identified in 2397 patients (0.83% incidence). There were 19 females and one male with an average age of 31.8 +/- 12.6. Involved sites included eight disseminated cases, six central nervous system, four lungs, one abdomen and one soft tissue. IFI contributed to a high mortality with 10 deaths (50%), and there were no survivors for the disseminated cases and Candida-infected patients. High activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 8) was noted in 50% of IFI episodes. The survival from IFI diagnosis to death was only 7.7 +/- 4.2 days, all in a rapid course. No statistical difference was found between survivors and non-survivors when comparing their SLEDAI. Eighty-five percent of IFI episodes under high dosages of corticosteroids therapy and 95% of patients had lupus nephritis. There was an increased risk of IFI in the lupus patients receiving high daily dosage of prednisolone therapy. Critical information from analyses of the present large series could be applied into clinical practices to reduce the morbidity and mortality in such patients.

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.

Objectives: To analyse the characteristic features of patients with coexistence of gouty arthritis and pyarthrosis at our university hospital in southern Taiwan, an area with high prevalence of hyperuricemia and gout., Methods: A retrospective chart review was performed for patients who had concomitant gouty and septic arthritis from July 1998 to June 2008. Clinical and laboratory data of these patients were analysed. Furthermore, a comparison was made with published cases in English literature., Results: Fourteen cases with coexistence of gouty arthritis and pyarthrosis have been identified during the past 10 years. There were 13 male and 1 female, all of Han Chinese in ethnicity, with ages ranging from 45 to 85 and an average of 63.7 years. At disease presentation, there were 11 oligoarticular cases (78.6%), 2 monoarticular cases (14.3%) and 1 polyarticular case (7.1%). Ankle and knee joints were most commonly involved. Bacteriological analyses demonstrated gram-positive cocci in 12 cases, of these 10 were oxacillin-sensitive Staphylococcus aureus (71.4%). Multiple tophi deposition was noted in 13 patients (92.9%) and among them 11 patients (84.6%) had associated chronic kidney disease., Conclusion: Different clinical presentations and bacteriological characteristics have been identified in the present series. While the mechanisms responsible for such a coexistence remain to be elucidated, these cases underline the importance of thorough evaluation of the aspirated synovial fluid. Our report adds a novel insight into the understanding of the clinical and microbiological manifestations of such a rare concurrence of gouty and septic arthritis.

Programmed death-1 (PD-1) was shown to deliver an inhibitory signal after binding to its ligands, PD-L1 (B7-H1) or PD-L2 (B7-DC). Recently, up-regulated expression of PD-1 molecule and/or its ligands was demonstrated in human diseases including rheumatoid arthritis and inflammatory colitis. The study aimed to investigate the expression and function of PD-1 and PD-1 ligands on circulating T cells, B cells and monocytes from patient with systemic lupus erythematosus (SLE). The results showed that patients with SLE had significantly increased percentages of PD-1-expressing CD3+T cells and CD19+B cells, PD-L1-expressing CD19+B cells and PD-L2-expressing CD14+B monocytes. In selected SLE patients and normal subjects, functional study of PD-1/ PD-1 ligands pathway on the production of cytokines by stimulated PBMC was examined. Blockages of PD-1 or PD-1 ligands substantially increased the production of IL-2, IFN-gamma and IL-10, the amplitude of increase roughly ranged from one to three times. There were no significant differences of the enhancing effects on cytokine production by blockage of PD-1/PDL pathway between SLE patients and normal subjects. The study indicates that there are no intrinsically defective expression and function of PD-1 and PD-1 ligands on PBMC in patients with SLE.

CD4+CD25+bright T cells played a crucial role in the suppression of immune response. Recently, decreased levels of CD4+CD25+bright T cells in the peripheral blood of patients with systemic lupus erythematosus were reported, suggesting the potential role of CD4+CD25+bright T cells in human autoimmune diseases. Primary Sjögren's syndrome (pSS) is another common human systemic autoimmune disease. The present study aimed to investigate the levels of CD4+CD25+bright T cells in pSS and to correlate their levels with some biomarkers of inflammation and immune activation. Thirty-three patients with pSS and 35 age- and sex-matched normal individuals were enrolled in the study. The flowcytometric method was applied in the measurement of CD4+CD25+bright T cells. The results showed that patients with pSS had statistically lower levels of CD4+CD25+bright T cells than normal controls, expressed either as absolute cell numbers (mean+/-SD: 47.07+/-25.53 cells/mm3 versus 79.55+/-34.56 cells/mm3, P<0.001) or as percentages of peripheral blood mononuclear cells (mean+/-SD: 2.79+/-1.06% versus 3.84+/-1.42%, P<0.001) or as percentages of CD4+ T cells (mean+/-SD: 7.85+/-2.62% versus 11.68+/-3.78%, P<0.005). Moreover, there were statistically significant inverse correlations between the levels of CD4+CD25+bright T cells and some parameters of inflammation or immune activation including erythrocyte sedimentation rate, C-reactive protein, IgG and rheumatoid factors. The result suggested that CD4+CD25+bright T cells were likely to play anti-inflammatory and immunosuppressive roles in the pathogenesis of pSS. However, the exact functions of decreased circulating CD4+CD25+bright T cells in pSS need further elucidated.

Osteoporosis, a condition of low bone mass and microarchitectural deterioration, results in fractures with minimal trauma. Secondary osteoporosis is defined as bone loss resulting from either specific clinical disorders or medications. Some medications that can induce osteoporosis are discussed. Specifically, this article reviews the pathogenesis of glucocorticoid-induced bone loss and demonstrates the means to successfully manage the condition with a combination of calcium and vitamin D supplementation and, depending on the severity of the bone loss, bisphosphonates or parathyroid hormone. In addition, the pathophysiology of bone loss from aromatase inhibitors in women, gonadotropin-releasing hormone agonists in men, anticonvulsant medications, and proton pump inhibitors is outlined. Finally, this review offers suggestions on evaluation and management of bone health in individuals treated with these medications for prolonged times.