OBJECTIVES:This study aimed to evaluate the associations of air pollution with disease activity and flare rate in patients with rheumatoid arthritis (RA). METHODS:This prospective cohort study included patients with RA who were treated at a tertiary medical centre in South Korea between January 2021 and December 2024. Air pollution exposure was estimated using monthly mean concentrations of 6 air pollutants (sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide, particulate matter [PM]10, and PM2.5). Disease activity and flares were recorded longitudinally at each outpatient visit. Associations between air pollution and RA disease activity or flare were analysed using linear and logistic generalised estimating equations, adjusting for demographic characteristics, serologic status, medication use, socioeconomic factors, and meteorological variables. As a sensitivity analysis, a case-crossover design using daily air pollutant concentrations preceding each visit was applied, with conditional logistic regression to assess within the same patient. RESULTS:A total of 12,583 outpatient visits from 1070 patients were analysed. Among 6 pollutants, PM2.5 was significantly associated with an increased risk of flare (adjusted odds ratio [OR]: 1.113 [95% CI: 1.017-1.218]) and with higher Disease Activity Score based on 28 joints (DAS28) with C-reactive protein (CRP), Clinical Disease Activity Index, 28-tender joint count, and 28-swollen joint count. In addition, the association between PM2.5 and DAS28-CRP was more pronounced among women and nonsmokers. In the case-crossover analysis, prolonged cumulative exposure to PM2.5 over >2 weeks was associated with an increased risk of RA flare. CONCLUSIONS:Exposure to air pollutants, particularly PM2.5, was associated with increased RA disease activity and flare risk. Further studies are warranted to determine whether improving air quality can reduce disease activity in patients with RA.

Although previous studies have demonstrated that high-dose glucocorticoids (GCs) significantly increase the risk of infection in patients with autoimmune inflammatory rheumatic diseases (AIRDs), the actual risk for individual patients varies depending on other clinical factors. This study aimed to develop and validate a scoring system for identifying patients at high risk of serious infection following high-dose GC treatment for AIRDs. Patients with AIRDs treated with prolonged (≥ 4 weeks) high-dose GCs (≥ 30 mg/day prednisone) were included from two referral hospitals. Primary outcome was 1-year incidence of serious infection. Cox regression with LASSO regularization was applied to select covariates for the final model from 19 prespecified factors. A scoring system was developed based on β-coefficients of covariates in the final model. In the derivation cohort (n = 1635), serious infection occurred in 153 patients, with an incidence rate (per 100 person-years) of 10.5 (95

Operating teams consisting of several team members still play a critical role in coping with off-normal conditions in socio-technical systems. Thus, various kinds of human reliability analysis methods have been suggested based on the consideration of diverse performance shaping factors that can affect the performance of team members. Unfortunately, since multiple performance shaping factors can vary across operating teams (i.e., crew-to-crew variability), it is crucial to figure out how to visualize this variability in a systematic way. In this regard, comparing the cultural characteristics of operating teams with their performance would be a good starting point. This study investigates how cultural characteristics can be correlated with the occurrence of unsafe acts based on empirical data collected from operating teams working in the main control room of Korean domestic nuclear power plants. The cultural characteristics of the operating teams were visualized using five Hofstede’s cultural indices and compared with the number of unsafe acts observed from simulated off-normal conditions. As a result, a statistically significant correlation is found between the occurrence of unsafe acts and one of the Hofstede’s indices. From this finding, it is expected that a relevant probe to scrutinize crew-to-crew variability could be soundly determined in future works.

OBJECTIVES:To develop a model for predicting flares after tapering the dose of tumour necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). METHODS:Data were obtained from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. In total, 526 patients who received the standard-dose TNFi for at least 1 year and tapered their dose were included in the derivation cohort. The main outcome was a flare occurrence defined as an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) score of ≥2.1 after 1 year of TNFi tapering. The final prediction model was validated using an independent cohort. RESULTS:Among 526 patients, 127 (24.1%) experienced flares. The final prediction model included negative human leucocyte antigen B27 (β = 1.088), inflammatory back pain (β = 1.072), psoriasis (β = 1.567), family history of SpA (β = 0.623), diabetes mellitus (β = 1.092), TNFi tapering by ≥50% of the standard-dose (β = 0.435), ASDAS-CRP at tapering (β = 1.029), and Bath Ankylosing Spondylitis Functional Index score at tapering (β = 0.194) as covariates. It showed an excellent discrimination performance (AUC = 0.828). According to the predictive risk, patients were classified into three groups (low-, intermediate- and high-risk). The probabilities of flares in these groups were 4.5%, 18.1% and 61.8%, respectively. The performance of the model in the validation cohort was also comparable. CONCLUSION:The established prediction model accurately predicted the risk of flares after TNFi dose tapering in patients with axSpA using eight simple clinical parameters, which could be helpful to select appropriate patients for tapering their TNFi without flare in daily clinical practice.

The TACOM (Task Complexity) measure was previously developed to quantify the complexity of tasks conducted by human operators in the main control room of nuclear power plants. The appropriateness of the TACOM measure was then confirmed in various validation studies mainly by comparing TACOM scores and operators' task performance times in analog-type main control rooms. However, the suitability of the measure has not yet been validated using operators' task performance times in digital-type main control rooms. This study aimed to further validate the suitability of the TACOM measure by analyzing task performance time data obtained from a digitalized full-scope simulator of a Korean domestic nuclear power plant and comparing the data with TACOM scores. The findings reveal a positive correlation between the task performance times in the digitalized main control room and the TACOM scores, meaning that the operators’ task performance time increases proportionally as the TACOM score increases. This strongly implies that the TACOM measure is also a reliable tool for predicting task complexity in a digitalized main control room.

Although patients with idiopathic inflammatory myopathy (IIM) have a higher cancer risk than the general population, this risk varies among IIM patients based on clinical factors such as IIM subtype, clinical features, and autoantibody profiles. This study aimed to establish a risk-stratification system to identify those with high-risk for cancer in patients with IIM. This study included 481 patients with IIMs from four independent cohorts in South Korea. The primary outcome was myositis-associated cancer, defined as cancers occurring within 3 years before or after the diagnosis of IIM. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) regularization was used to select predictors from 24 prespecified factors for the multivariable model. A scoring system, entitled the SCRIM score, was established based on the β coefficient of each predictor in the final model. A conditional inference tree analysis was used to identify the optimal cut-off point for group classifications. The cancer risk of each group compared to that of the general population was assessed using standardized incidence ratio (SIR), which was calculated using the 2022 age-matched general population in South Korea as the reference. In the study population, 12.9

OBJECTIVES:The study objective was to determine if a common single nucleotide polymorphism in the interleukin 6 (IL-6) receptor (rs2228145, p.Asp358Ala) predicted treatment response to tocilizumab in giant cell arteritis (GCA). METHODS:Genetic sequencing of the rs2228145 locus was performed in 2 independent cohorts of patients with GCA. Peripheral blood mononuclear cells (PBMCs) from patients and controls were evaluated for expression of the interleukin 6 receptor (IL-6R) and its coreceptor, gp130, using flow cytometry. The same PBMCs were stimulated with IL-6 and evaluated for downstream targets of IL-6: STAT3 phosphorylation (pSTAT3) and IL-17A expression. RESULTS:In total, 100 patients with GCA were included (derivation cohort n = 58; validation cohort n = 42). The rs2228145 variant predicted tocilizumab response in each cohort. In the derivation cohort, a gene dose-dependent response was observed with a 36% response rate in the homozygous patients and 95% response rate in patients without the variant (P = .003). In the validation cohort, tocilizumab response rates were 50% for homozygotes and 85% for patients without the variant (P = .04). pSTAT3 levels were significantly increased in response to IL-6 stimulation in a gene dose-dependent manner in CD4 T cells from patients with GCA but not controls. CD4 T cells from patients with GCA had significantly higher membrane expression of gp130 than healthy controls, and response to IL-6 correlated with gp130 expression. IL-17 producing CD4 T cells were increased in a gene dose-dependent response to IL-6 (P < .01). CONCLUSIONS:The rs2228145 variant is associated with decreased treatment response to tocilizumab and worse outcomes in GCA by enhancing CD4 T cell response to IL-6.

The two papers in series deal with development of a new human reliability analysis (HRA) method, SAM-L2HRA, for evaluating severe accident management (SAM) strategies utilizing portable equipment for preventing and mitigating severe accidents. The first paper, Part I, introduces technical background for developing SAM-L2HRA, including identification of task characteristics of severe accident management guidelines (SAMGs) and the critical steps of individual SAM strategies with their likelihood of human errors and decision-making associated with each strategy to be included in the SAM-L2HRA framework. Based on the identified task characteristics and context of SAMGs, an approach to Level 2 HRA based on the technical support center (TSC) SAMGs, SAM-L2HRA, is outlined. To have more elaborate basis for SAM-L2HRA, the Table-Top eXercise (TTX) experiments have been designed and conducted under postulated severe accident scenarios, and the results and insights gained from the experiments and interviews with the subjects were summarized.

Background/Aims:To compare the efficacy and safety of fexuprazan and lansoprazole for preventing peptic ulcers (PUs) induced by nonsteroidal anti-inflammatory drugs (NSAIDs). Methods:This multicenter, double-blind, randomized, active-controlled study was conducted across 32 hospitals in South Korea. Patients with musculoskeletal disease requiring long-term treatment with celecoxib, naproxen, or meloxicam were randomized to receive either fexuprazan 20 mg/day (n=212) or lansoprazole 15 mg/day (n=211) for 24 weeks. The primary endpoint was the occurrence of PUs, which were confirmed via esophagogastroduodenoscopy (EGD), with a non-inferiority margin of 8.3%. Only ulcers that developed during the treatment period were examined in the analysis. The occurrence of gastroduodenal bleeding was also monitored via EGD, and symptoms were assessed by using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM). Adverse events were recorded during the study. Results:The incidence rate of EGD-confirmed PUs at week 24 was 1.16% in the fexuprazan group and 2.76% in the lansoprazole group, with a between-group difference of -1.64% (95% confidence interval, -4.52% to 1.25%), demonstrating non-inferiority. No patients presented with gastroduodenal bleeding. No significant between-group differences were found in the PAGI-SYM scores (leastsquare mean difference in the total score at week 24, -0.42; 95% confidence interval, -2.48 to 1.64; p=0.69). There were low rates of adverse drug reactions in the fexuprazan and lansoprazole groups (8.57% vs 4.78%, respectively p=0.12). Conclusions:Given its non-inferiority to lansoprazole and similar safety profile, fexuprazan is a promising alternative for the prevention of NSAID-induced PUs (ClinicalTrials.gov identifier NCT04784910).

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. Despite advances in biologic therapies targeting inflammatory mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)6, Janus kinase (JAK), and B cells, many patients do not respond adequately, emphasizing the need for deeper insights into RA pathogenesis. Research highlights the intricate interplay of genetic and epigenetic factors driving immune dysregulation. The breakdown of immune tolerance, often initiated in mucosal sites such as the gut, lung, and oral cavity, promotes the citrullination of antigens, leading to anti-citrullinated protein antibody production and subsequent immune activation. Single-cell and multiomics approaches have shed light on underexplored immune cell types, such as T peripheral helper cells, CD4+/CD8+ cytotoxic T cells, and autoreactive B cells, broadening the understanding beyond traditionally studied Th17, Th1 cells, macrophages, and fibroblast-like synoviocytes. Future basic research in RA should prioritize elucidating the mechanisms behind peripheral tolerance breakdown, the pathogenesis of seronegative RA, and the molecular pathways driving refractory and recurrent disease. Moreover, leveraging multi-omics approaches to dissect disease heterogeneity will be pivotal for advancing personalized treatment strategies and improving long-term outcomes in RA patients.

Human Factors validation is a critical step in the design and development of complex human-technology systems such as nuclear power plants. Unfortunately, frequent validation challenges are reported by designers, vendors, and authorities, and this presents challenges when determining the acceptability of system design due to inefficient test scenarios, and inadequate human performance measures. This means that whilst existing guides and standards attempt to provide technical advice and a common basis for different stakeholders, validation teams continue to report limitations in the levels of support provided. This paper discusses a number of these human factors validation challenges and makes recommendations for future research to improve the technical basis of guides and standards.

BackgroundThe adjuvanted herpes zoster subunit vaccine has shown good efficacy and safety in the general population. However, its effectiveness has not been comprehensively assessed in patients with systemic lupus erythematosus (SLE). This study aimed to evaluate the immunogenicity and safety of the adjuvanted herpes zoster subunit vaccine in patients with SLE.MethodsThis single-centre, randomised, double-blind, placebo-controlled, trial was done at the rheumatology outpatient clinic at Seoul National University Hospital, South Korea. Patients (aged ≥19 years) with clinically stable SLE and previous exposure (≥4 weeks) to immunosuppressive drugs were randomly assigned (4:1) via a central interactive web response system to receive herpes zoster subunit vaccine or placebo (0·5 mL intramuscular injection) at weeks 0 and 8. Investigators and participants were masked to intervention and group assignment. Anti-glycoprotein E antibody titres and glycoprotein E-specific cell-mediated vaccine responses were evaluated at baseline and at week 8 after the first dose, and at week 4, week 26, and week 52 after the second dose using enzyme-linked immunosorbent assay and flow cytometry, respectively. Reactogenicity, SLE disease activity, including Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rate, were examined. The primary outcome was the proportion of patients with a positive humoral vaccine response 4 weeks after the second dose. The primary and safety analyses were done in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT06001606.FindingsBetween June 14, and July 19, 2023, 65 patients with SLE were enrolled, of whom 52 were randomly assigned to the herpes zoster subunit vaccine and 13 to placebo. 49 patients in the vaccine group and 11 patients in the placebo group were included in the modified intention-to-treat population. 56 (93%) of 60 patients were women and four (7%) were men. Mean age was 48·7 years (SD 11·4). The proportion of participants with a humoral vaccine response at 4 weeks after the second dose was significantly higher in the vaccine group (48 [98%] of 49 participants) than the placebo group (none [0%] of 11 patients; p<0·0001). More patients in the vaccine group than placebo group reported injection site reactions (42 patients vs two patients), fever (ten vs none), and fatigue (26 vs two). There were no differences in Systemic Lupus Erythematosus Disease Activity Index 2000 and British Isles Lupus Assessment Group-flare rates between the groups. There were no treatment-related deaths.InterpretationThe herpes zoster subunit vaccine induces humoral and cellular immunity against herpes zoster with a good safety profile in patients with SLE. A larger study is warranted to assess the efficacy of vaccines to prevent herpes zoster in patients with SLE.FundingMinistry of Science and ICT, The Government of the Republic of Korea.