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Altered gut microbiota is linked to systemic lupus erythematosus (SLE), but its association with disease development, disease activity, and post-intervention changes remains unclear. We compared new-onset SLE (NOSLE, n = 25), SLE in remission (RemSLE, n = 30), and healthy controls (HC, n = 30) cross-sectionally and conducted the first longitudinal analysis of NOSLE patients (n = 22) from pre-intervention to remission over 12 months. Significant β-diversity differences were observed in both NOSLE and RemSLE compared to HC, but not between NOSLE and RemSLE. Only four operational taxonomic units (OTUs) were enriched in NOSLE versus HC. However, 26 OTUs, including butyrate-producing bacteria (BPB), were depleted, and seven (including five BPBs) remained depleted in RemSLE compared to HC. OTUs positively and negatively correlated with disease activity were also identified. Longitudinal analysis revealed a reversal of several OTUs altered at onset and an increase in Streptococci, unrelated to the disease. Significant β-diversity differences were observed in patients with anti-SSA or anti-RNP antibodies and those with complement reduction compared to their counterparts. Our study identified gut microbiota alterations, including BPB depletion, in SLE regardless of onset or remission status, bacteria linked to disease activity, and a reversal of disease-associated bacteria along with the enrichment of Streptococci through intervention., Competing Interests: Declarations. Competing interests: EW received a grant from GSK plc. All other authors declare no competing interests., (© 2024. The Author(s).)

Objective: Few studies have explored whether the involvement of patients in shared decision-making (SDM) is beneficial to the management of systemic lupus erythematosus (SLE). Therefore, this study investigated the relationship between patient participation in SDM and their trust in physicians using data from the Trust Measurement in Physicians and Patients With SLE (TRUMP2-SLE) study., Methods: Data regarding the nine-item Japanese version of the Shared Decision-Making Questionnaire (SDM-Q-9) scores, Trust in Physician Scale (TIPS) scores, and Abbreviated Wake Forest Physician Trust Scale (A-WFPTS) scores for interpersonal trust in a physician and trust in the medical profession were collected from patients with SLE who visited the outpatient clinics of five facilities in Japan through a self-administered questionnaire. The relationships among these scores were analyzed by general linear models with cluster-robust variance., Results: This study included 433 patients with SLE. The median baseline TIPS and A-WFPTS (attending physician version) scores were 82 (73-93) and 80 (70-95), respectively. A higher baseline SDM-Q-9 score was correlated with an increase in the TIPS score at one year (coefficient per 10-point [pt] increase, 0.94 pts, 95% confidence interval [CI] 0.16-1.72). A higher baseline SDM-Q-9 score was correlated with a higher A-WFPTS score for interpersonal trust (coefficient per 10-pt increase, 2.20 pts, 95% CI 1.44-2.96). The baseline SDM-Q-9 score was also correlated with an increase in the general physician version of the A-WFPTS score at one year (coefficient per 10-pt increase, 1.29 pts, 95% CI 0.41-2.18)., Conclusion: Engagement of patients with SLE in SDM elevates their trust in the attending physicians and health care providers, potentially enhancing doctor-patient relationships and overall health care trust., (© 2024 American College of Rheumatology.)

Background: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis., Methods: This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage., Results: Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis., Conclusion: This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use., Competing Interests: Declarations Ethics approval and informed consent This study was conducted in accordance with the Declaration of Helsinki and Ethical Guidelines for Epidemiologic Research in Japan. The study protocol was approved by the Ethics Committee of Kakogawa Central City Hospital (authorization number: 2021–04). The patients provided written informed consent to participate in the and permission to publish their data. Consent for publication Not applicable. Competing interests KS received speaker fees from Glaxo Smith Kline and a research grant from Pfizer Inc. TY received speaker fees from Glaxo Smith Kline., (© 2024. The Author(s).)

Background: Patient trust plays a central role in the patient-physician relationship. This study aimed to determine whether the number of outpatient visits with a covering rheumatologist is associated with patient trust in their usual rheumatologist., Methods: Japanese adults with systemic lupus erythematosus (SLE) who met the 1997 revised classification criteria of the American College of Rheumatology and had outpatient visits with a covering rheumatologist in the past year were included. We used the 11-item Japanese version of the modified Trust in Physician Scale (range 0-100) to assess patient trust. A general linear model with cluster-robust variance estimation was used to evaluate the association between the number of outpatient visits with covering rheumatologists and the patient's trust in their usual rheumatologist., Results: Of the 515 enrolled participants, 421 patients with SLE were included in our analyses. Patients were divided into groups according to the number of outpatient visits with a covering rheumatologist in the past year as follows: no visits (59.9%; reference group), one to three visits (24.2%; low-frequency group), and four or more visits (15.9%; high-frequency group). The median Trust in Physician Scale score was 81.8 (interquartile range: 72.7-93.2). Both the low-frequency group (mean difference: -3.03; 95% confidence interval [CI] -5.93 to -0.80) and high-frequency group (mean difference: -4.17; 95% CI -7.77 to -0.58) exhibited lower trust in their usual rheumatologist., Conclusion: This study revealed that the number of outpatient visits with a covering rheumatologist was associated with lower trust in a patient's usual rheumatologist., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki, and the study protocol was approved by the Graduate School of Medical and Dental Sciences of Okayama University and the Okayama University Hospital Ethics Committee (approval number: 2204–020). Consent for publication All patients provided informed consent before enrolment. Competing interests Dr. Kurita reported receiving grants from the Japan Society for the Promotion of Science, consulting fees from GlaxoSmithKline K.K., and payments for speaking at and participating in educational events from Chugai Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, and the Japan College of Rheumatology. Dr. Sada reported receiving a research grant from Pfizer, Inc. and a payment for speaking at and participating in educational events from GlaxoSmithKline K.K. Dr. Wada reported receiving speaker honoraria from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Kyowa Kirin, Novo Nordisk, and Mitsubishi Tanabe, and received grant support from Bayer, Chugai, Kyowa Kirin, Otsuka, Shionogi, Sumitomo, and Mitsubishi Tanabe. Dr. Matsumoto reported receiving grants from Asahi Kasei Pharma, Taisho, and AbbVie; received speaker honoraria from Astra Zeneca, Asahi Kasei Pharma, GlaxoSmithKline, and Pfizer, Inc.; and received a payment for participating in educational events from GlaxoSmithKline., (© 2024. The Author(s).)

Objectives: A quality indicator (QI) for the treatment of systemic lupus erythematosus (SLE) during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a QI for SLE associated with pregnancy and childbirth., Methods: To identify candidate QIs, we conducted a systematic literature review on the development of QIs for SLE related to pregnancy and childbirth and on clinical practice guidelines. Candidate QI items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as QIs. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related SLE QIs., Results: Four articles on SLE QI development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate QIs were extracted that were limited to items related to pregnancy and childbirth and 41 items were selected on which all panel members agreed., Conclusion: We developed pregnancy-related SLE QIs using the RAND/UCLA method and selected 41 items, which could be used clinically., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objective: Late-onset systemic lupus erythematosus (LoSLE) is known to possess characteristics different from those of early-onset SLE (EoSLE), thereby making their diagnosis difficult. This study aimed to assess the characteristic features of LoSLE in Japan, a model country with a super-aged society., Methods: Data were obtained from the Lupus Registry of Nationwide Institutions, which includes a multicenter cohort of patients with SLE in Japan who satisfied the 1997 American College of Rheumatology revised classification criteria for SLE. Data were compared between patients with LoSLE (≥50 years old at onset) and EoSLE (<50 years old at onset). To identify factors associated with LoSLE, binary logistic regression was used for the multivariate analysis, and missing values were complemented by multiple imputations. We also conducted a sub-analysis for patients diagnosed within 5 years of onset., Results: Out of 929 enrolled patients, 34 were excluded owing to a lack of data regarding onset age. Among the 895 remaining patients, 100 had LoSLE, whereas 795 had EoSLE. The male-to-female ratio was significantly higher in the LoSLE group than in the EoSLE group (0.32 vs 0.11, p < 0.001). With respect to SLEDAI components at onset, patients with LoSLE exhibited a higher frequency of myositis (11.9% vs 3.75%, p = 0.031), lower frequency of skin rash (33.3% vs 67.7%, p < 0.001), and lower frequency of alopecia (7.32% vs 24.7%, p = 0.012). No significant differences in overall disease activity at onset were observed between the two groups. Regarding medical history, immunosuppressants were more commonly used in EoSLE. A multivariate analysis revealed that a higher male proportion and a lower proportion of new rash at onset were independent characteristic features of LoSLE. We also identified late onset as an independent risk factor for a high SDI score at enrollment and replicated the result in a sub-analysis for the population with a shorter time since onset., Conclusions: We clarified that LoSLE was characterized by a higher male proportion, a lower frequency of skin rash and a tendency to organ damage. Now that the world is faced with aging, our results may be helpful at diagnosis of LoSLE., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Ken-ei Sada received a speaker’s fee from GlaxoSmithKline PLC and research grants from Pfizer Inc. Yohei Kirino received a speaker’s fee from Amgen and Novartis and research funding from Nippon Shinyaku. Ryusuke Yoshimi received a speaker’s fee from GlaxoSmithKline PLC, AstraZeneca PLC, and Sanofi S.A.

Objectives: This study investigated the clinically relevant factors for headaches in patients with systemic lupus erythematosus (SLE) using a registry from a Japanese multicenter cohort., Methods: This cross-sectional study analysed the clinical information of patients with SLE who experienced headache episodes using the Migraine Disability Assessment (MIDAS) questionnaire. Significant findings in the comparisons between patients with headache (HA patients) and those without headache (non-HA patients) and in the comparisons depending on the grades of headache-induced disability in daily life based on the MIDAS scores were evaluated. Multivariate logistic regression analyses were performed to identify the relevant factors for headache., Results: We analyzed 369 patients (median age, 45 years; female, 90.8%), including 113 HA patients who were significantly younger than non-HA patients ( p < .005). HA patients had significantly higher frequencies of photosensitivity, rashes, and mucosal ulcers than non-HA patients ( p < .05). Age and photosensitivity were significantly associated with headache (odds ratio (OR) 0.93, 95% confidence interval (CI) 0.95-0.99; OR 2.11, 95% CI 1.29-3.49, respectively). In the HA patients, hypocomplementemia was significantly associated with a disability of more than mild grade (OR 2.89, 95% CI 1.14-7.74), while rash was significantly observed in those presenting with moderate and severe disability., Conclusion: This study suggests that photosensitivity is a relevant manifestation of headache in patients with SLE. Persistent hypocomplementemia can contribute to headache-induced disability in daily life, whereas a rash may be a dominant manifestation in patients presenting with moderate/severe headache-induced disability., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The European League Against Rheumatism recommends that the disease activity of systemic lupus erythematosus should be stable before pregnancy because complications and disease flares increase if pregnancy occurs while disease activity is high. However, some patients have ongoing serological activity even after treatment. Herein, we investigated how physicians decide on the acceptability of pregnancy in patients showing only serological activity., Methods: A questionnaire was administered from December 2020 to January 2021. It included the characteristics of physicians, facilities, and the allowance for pregnancies of patients using vignette scenarios., Results: The questionnaire was distributed to 4946 physicians, and 9.4% responded. The median age of respondents was 46 years, and 85% were rheumatologists. Pregnancy allowance was significantly affected by the duration of the stable period and status of serological activity [duration: proportion difference 11.8 percentage points (p.p.), P < .001; mild activity: proportion difference -25.8 p.p., P < .001; high activity: proportion difference -65.6 p.p., P < .001]. For patients with high-level serological activity, 20.5% of physicians allowed pregnancy if there were no clinical symptoms for 6 months., Conclusions: Serological activity had a significant effect on the acceptability of pregnancy. However, some physicians allowed patients with serological activity alone to become pregnant. Further observational studies are required to clarify such prognoses., (© Japan College of Rheumatology 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Previous studies have shown conflicting evidence regarding the incidence of cancer in patients with systemic lupus erythematosus (SLE) compared with that in healthy individuals. Calcineurin inhibitors (CNIs) such as cyclosporine and tacrolimus have been widely used to treat SLE; however, their effects on cancer risk remain unclear. We aimed to investigate the incidence of cancer in patients with SLE and determine the potential association between CNI use and cancer risk., Methods: The standardized incidence ratio (SIR) of cancer among patients with lupus in the Lupus Registry of Nationwide Institutions (LUNA) was calculated based on the age-standardized incidence rate of cancer reported by Japan's Ministry of Health, Labour and Welfare. We also examined the association between CNI exposure and cancer risk, while considering potential confounding factors. The analysis accounted for confounding variables such as age, sex, smoking history, maximum glucocorticoid dose, treatment history with cyclophosphamide, ongoing hydroxychloroquine, Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI) value (excluding cancer occurrence), comorbidity of diabetes mellitus, and smoking history., Results: The study included 704 patients with SLE (625 females; 88.8%) with a median age of 44 years [interquartile range (IQR) = 34-55] years. The median past maximum glucocorticoid dose was 40 mg/day [IQR = 30-60 mg/day], and the SDI at registration was 1 [IQR = 0-2]. Among the patients, 246 (35.1%) had smoking histories, and 38 (5.4%) experienced cancer complications. Gynecological malignancies accounted for 63.2% of all cancers. The SIR of cancer in the LUNA cohort was 1.08 (95% confidence interval [CI] = 0.74-1.43). No statistically significant risks of cancer were found in relation to CNI treatment history; the odds ratio using multiple logistic regression was 1.12 (95% CI = 0.42-3.00), the risk ratio using standardization was 1.18 (95% CI = 0.47-2.16), and the risk ratio using inverse probability weighting was 1.8 (95% CI = 0.41-4.66)., Conclusions: The incidence of cancer in patients with SLE in the LUNA cohort did not significantly differ from that in the general population. These findings suggest that CNI treatment in this cohort did not pose a risk factor for cancer development., (© 2024. The Author(s).)

Objective: Differences in communication styles based on physicians' personality traits have been identified, particularly in primary care, and these physician-related factors can be important in building patient-physician trust. This study examined the effects of rheumatologists' personality traits on patients' trust in their attending rheumatologists., Methods: This cross-sectional study included adult Japanese patients with systemic lupus erythematosus (SLE) at 5 academic medical centers between June 2020 and August 2021. The exposures were the Big 5 personality traits (ie, extraversion, agreeableness, openness, conscientiousness, and emotional stability) of attending rheumatologists using the Japanese version of the 10-Item Personality Inventory scale (1-7 points each). The outcome was the patients' trust in their attending rheumatologist using the Japanese version of the 5-item Wake Forest Physician Trust Scale (0-100 points). A general linear model was fitted., Results: The study included 505 patients with a mean age of 46.8 years; 88.1% were women. Forty-three attending rheumatologists (mean age: 39.6 years; 23.3% female) were identified. After multivariable adjustment, higher extraversion and agreeableness were associated with higher trust (per 1-point increase, 3.76 points [95% CI 1.07-6.45] and 4.49 points [95% CI 1.74-7.24], respectively), and higher conscientiousness was associated with lower trust (per 1-point increase, -2.17 points [95% CI -3.31 to -1.03])., Conclusion: Whereas higher extraversion and agreeableness of attending rheumatologists led to higher patient trust in their rheumatologist, overly high conscientiousness may lead to lower trust resulting from the physicians' demand of responsibility and adherence to instructions from patients with SLE., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: Providing appropriate health information to patients with systemic lupus erythematosus (SLE) is advantageous in the treatment decision-making process. We aimed to investigate how online health information-seeking behaviors affect shared decision-making (SDM) in patients with SLE., Methods: This cross-sectional study included 464 patients with SLE from five institutions. The main exposure was time spent on the internet per day, divided into four categories (none, <1 h, 1- < 2 h, ≥2 h). Participants categorized their preferred first source of health information as physicians, the internet, or other media. The outcome was the degree of SDM measured via the 9-item Shared Decision-Making Questionnaire (SDM-Q-9). A general linear model was applied., Results: Compared to no internet use, longer internet use was associated with a higher SDM-Q-9 score: <1 h, 6.9 points (95% confidence interval [CI] 0.32 to 13.6) and ≥2 h, 8.75 points, (95% CI 0.61 to 16.9). The SDM-Q-9 did not differ between the individuals who chose physicians and those who chose the Internet as their preferred first source of health information (-2.1 points, 95% CI -6.7 to 2.6). Individuals who chose other media had significantly lower SDM-Q-9 scores than those who chose physicians (-7.6 points, 95% CI -13.2 to -1.9)., Conclusions: The present study suggests that SDM between physicians and patients is positively associated with online information-seeking behavior, with no negative influence associated with accessing the Internet before clinical consultations. Rheumatologists may need to introduce their patients to websites offering high-quality health information to establish a good physician-patient relationship for SDM., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: NK is a member of the Committee on Clinical Research, Japan College of Rheumatology, and has received grants from the Japan Society for the Promotion of Science, consulting fees from GlaxoSmithKline K.K., and payments for speaking and educational events from Chugai Pharmaceutical Co. Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, and Japan College of Rheumatology. K. Sada has received a research grant from Pfizer Inc. and payments for speaking and educational events from GlaxoSmithKline K.K. Other authors declare no competing interests.

Objectives: There is a high prevalence of burnout among rheumatologists. Grit, which is defined as possessing perseverance and a passion to achieve long-term goals, is predictive of success in many professions; however, whether grit is associated with burnout remains unclear, especially among academic rheumatologists, who have multiple simultaneous responsibilities. Thus, the purpose of this study was to examine the associations between grit and self-reported burnout components-professional efficacy, exhaustion, and cynicism-in academic rheumatologists., Methods: This cross-sectional study involved 51 rheumatologists from 5 university hospitals. The exposure was grit, measured using mean scores for the 8-item Short Grit Scale (range, 1-5 [5 = extremely high grit]). The outcome measures were mean scores for 3 burnout domains (exhaustion, professional efficacy, and cynicism; range, 1-6; measured using the 16-item Maslach Burnout Inventory-General Survey). General linear models were fitted with covariates (age, sex, job title [assistant professor or higher vs lower], marital status, and having children)., Results: Overall, 51 physicians (median age, 45 years; interquartile range, 36-57; 76% men) were included. Burnout positivity was found in 68.6% of participants (n = 35/51; 95% confidence interval [CI], 54.1, 80.9). Higher grit was associated with higher professional efficacy (per 1-point increase; 0.51 point; 95% CI, 0.18, 0.84) but not with exhaustion or cynicism. Being male and having children were associated with lower exhaustion (-0.69; 95% CI, -1.28, -0.10; p = 0.02; and -0.85; 95% CI, -1.46, -0.24; p = 0.006). Lower job title (fellow or part-time lecturer) was associated with higher cynicism (0.90; 95% CI, 0.04, 1.75; p = 0.04)., Conclusions: Grit is associated with higher professional efficacy among academic rheumatologists. To prevent burnout among staff, supervisors who manage academic rheumatologists should assess their staff's individual grit., Competing Interests: N.K. is a member of the Committee on Clinical Research, Japan College of Rheumatology, and has received grants from the Japan Society for the Promotion of Science, consulting fees from GlaxoSmithKline K.K., and payments for speaking at and participating in educational events from Chugai Pharmaceutical Co, Ltd, Sanofi K.K., Mitsubishi Tanabe Pharma Corporation, and the Japan College of Rheumatology. K.S. received a research grant from Pfizer Inc and a payment for speaking at and participating in educational events from GlaxoSmithKline K.K. The other authors declare that they have no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Infection is a leading cause of death in patients with systemic lupus erythematosus (SLE). Alt hough hydroxychloroquine (HCQ) has been reported to inhibit infection, evidence from Asian populations remains insufficient. We investigated this effect in Japanese SLE patients., Methods: Data from the Lupus Registry of Nationwide Institutions were used in this study. The patients were ≥20 years old and met the American College of Rheumatology (ACR) classification criteria revised in 1997. We defined "severe infections" as those requiring hospitalization. We analyzed the HCQ's effect on infection suppression using a generalized estimating equation (GEE) logistic regression model as the primary endpoint and performed a survival analysis for the duration until the first severe infection., Results: Data from 925 patients were used (median age, 45 [interquartile range 35-57] years; female, 88.1%). GEE analysis revealed that severe infections were significantly associated with glucocorticoid dose (odds ratio [OR] 1.968 [95% confidence interval, 1.379-2.810], p <0.001), immunosuppressants (OR 1.561 [1.025-2.380], p =0.038), and baseline age (OR 1.043 [1.027-1.060], p <0.001). HCQ tended to suppress severe infections, although not significantly (OR 0.590 [0.329-1.058], p =0.077). Survival time analysis revealed a lower incidence of severe infections in the HCQ group than in the non-HCQ group ( p <0.001). In a Cox proportional hazards model, baseline age (hazard ratio [HR] 1.029 [1.009-1.050], p =0.005) and HCQ (HR 0.322 [0.142-0.728], p =0.006) were significantly related to incidence., Conclusion: HCQ may help extend the time until the occurrence of infection complications and tends to decrease infection rates., Competing Interests: KS received a speaker’s fee from GlaxoSmithKline PLC and research grants from Pfizer Inc. YKi received a speaker’s fee from Amgen and Novartis and research funding from Nippon Shinyaku. RY received a speaker’s fee from GlaxoSmithKline PLC, AstraZeneca PLC, and Sanofi S.A. The remaining 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 © 2023 Hidekawa, Yoshimi, Saigusa, Tamura, Kojitani, Suzuki, Sakurai, Yoshioka, Sugiyama-Kawahara, Kunishita, Kishimoto, Higashitani, Sato, Komiya, Nagai, Hamada, Maeda, Tsuchida, Hirahara, Soejima, Takase-Minegishi, Kirino, Yajima, Sada, Miyawaki, Ichinose, Ohno, Kajiyama, Sato, Shimojima, Fujiwara and Nakajima.)

Objective: Poor medication adherence among patients with SLE is a critical problem associated with adverse outcomes. This study examined the relationship between trust in one's physician and goal-oriented thinking, hope and medication adherence among Japanese patients with SLE who were ethnically matched to their physicians., Methods: This cross-sectional study was conducted in the rheumatology outpatient clinics at five academic centres. Patients with SLE who were prescribed oral medications were included. The main exposures were trust in one's physician measured via the 5-item Japanese version of the Wake Forest Physician Trust Scale and the 18-item Health-related Hope Scale, with each score ranging from 0 to 100 points. Medication adherence was measured using the 12-item Medication Adherence Scale with scores ranging from 5 to 60 points. A general linear model was created after adjusting for demographics, socioeconomic status, disease activity, disease duration, basic health literacy, depression, medication variables, experiencing adverse effects and concerns regarding lupus medications., Results: Altogether, 373 patients with SLE were included. The mean age of the patients was 46.4 years; among them, 329 (88.2%) were women. Both trust in one's physician (per 10-point increase: 0.86, 95% CI 0.49, 1.22) and the Health-related Hope score (per 10-point increase: 0.66, 95% CI 0.35, 0.97) were associated with better medication adherence., Conclusions: This study demonstrated that patients' health-related hope and trust in their rheumatologist were both associated with better medication adherence in SLE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Although personality characteristics of patients with SLE affect their disease activity and damage, it is unclear whether those of attending physicians affect the outcomes of patients with SLE. Grit is a personality trait for achieving long-term goals that may influence the decision-making for continuing treatment plans for patients. We aimed to evaluate the relationship between the grit of attending physicians and achievement of treatment goals in patients with SLE., Methods: This cross-sectional study was conducted at five referral hospitals. The main exposure was 'consistency of interest' and 'perseverance of effort' of the attending physicians, measured by the Short Grit Scale. The primary outcome was achievement of a lupus low disease activity state (LLDAS). The association between physicians' grit score and LLDAS was analysed by generalized estimating equation (GEE) logistic regression with cluster robust variance estimation, with adjustment for confounders., Results: The median (interquartile range) total, consistency and perseverance scores of 37 physicians were 3.1 (2.9-3.6), 3.3 (2.8-3.8) and 3.3 (3.0-3.5), respectively. Among the 386 patients, 154 (40%) had achieved LLDAS. Low consistency score (≤2.75) in physicians was related to LLDAS achievement independently using GEE logistic regression. The score of the question 'I often set a goal but later choose to pursue a different one' was significantly higher in patients achieving LLDAS., Conclusions: Difficulty of attending physicians to change treatment goals might be related to lower LLDAS achievement in patients with SLE., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Patients who trust their physicians have been shown to demonstrate good medication adherence, self-management, and favorable disease outcomes. This study examines how trust in physicians is affected by functional health literacy (HL) and by broader concepts of HL, including communicative HL and critical HL, among patients with systemic lupus erythematosus (SLE)., Methods: This was a cross-sectional study using baseline data from the Trust Measurement for Physicians and Patients with SLE (TRUMP2-SLE) study, an ongoing multicenter cohort study conducted at 5 academic centers. The 14-item Functional, Communicative, and Critical Health Literacy Scale assessed the 3 dimensions of HL; each item of the scale was scored on a 4-point Likert scale, ranging from 1 to 4. Outcomes were trust in one's physician and trust in physicians in general using the 5-item Wake Forest Physician Trust Scale, which ranged from 0 to 100 points. General linear models were fit., Results: A total of 362 patients with SLE were included. Trust in one's physician increased with higher functional and communicative HL (per 1-point increase: mean difference 3.39, 95% CI 0.39-6.39, and mean difference 5.88, 95% CI 2.04-9.71, respectively). Trust in physicians in general increased with higher communicative HL and decreased with higher critical HL (per 1-point increase: mean difference 7.09, 95% CI 2.34-11.83, and mean difference -6.88, 95% CI -11.72 to -2.04, respectively). Longer internet use was associated with both higher communicative and critical HL., Conclusion: The findings suggest that rheumatologists need to improve their communication to match each patient's HL, which may foster trust and lead to improved self-management and outcomes in SLE. They also suggest that the formation of the rheumatologist-patient relationship may negate the effect of high critical HL in building trust., (Copyright © 2023 by the Journal of Rheumatology.)

Objective: Fatigue is one of the most common complaints and is a potentially modifiable issue in systemic lupus erythematosus (SLE). Studies suggest that alcohol consumption has a protective effect against the development of SLE; however, an association between alcohol consumption and fatigue in patients with SLE has not been studied. Here, we assessed whether alcohol consumption was associated with fatigue using lupus patient-reported outcomes (LupusPRO)., Methods: This cross-sectional study, conducted between 2018 and 2019, included 534 patients (median age, 45 years; 87.3% female) from 10 institutions in Japan. The main exposure was alcohol consumption, which was defined as the frequency of drinking [<1 day/month (none group), ≤1 day/week (moderate group), and ≥2 days/week (frequent group)]. The outcome measure was the Pain Vitality domain score in LupusPRO. Multiple regression analysis was performed as the primary analysis after adjusting for confounding factors, such as age, sex, and damage. Subsequently, the same analysis was performed as a sensitivity analysis after multiple imputations (MIs) for missing data ( n = 580)., Results: In total, 326 (61.0%) patients were categorized into the none group, 121 (22.7%) into the moderate group, and 87 (16.3%) into the frequent group. The frequent group was independently associated with less fatigue compared with none group [β = 5.98 (95% CI 0.19-11.76), p = 0.04], and the results did not substantially deviate after MI., Conclusions: Frequent drinking was associated with less fatigue, which highlights the need for further longitudinal studies focusing on drinking habits in patients with SLE.

Introduction: Lupus nephritis (LN) is more prevalent in patients with SLE of Asian ethnicity than in Caucasian patients. Belimumab became available in Japan in 2017 to treat patients with SLE, including those with LN. In the BLISS-LN trial (NCT01639339), belimumab showed a favourable effect on renal outcomes when combined with standard therapy (ST) starting at the induction treatment phase for active LN, but real-world effectiveness of belimumab in LN has not been extensively studied. Here we describe the protocol for the MOONLIGHT (post-Marketed effectiveness of belimumab cOhOrt and JapaN Lupus NatIonwide ReGistry (LUNA) coHorT) study, which will use data from a Japan postmarketing surveillance study and the Lupus Registry of Nationwide Institutions (LUNA) to evaluate the real-world effectiveness of belimumab plus ST versus ST alone in patients with a history of active LN who are not in the induction phase., Methods and Analysis: This multicentre, retrospective, observational study (GSK Study 214710) will enrol adults with SLE and a history of active LN, holding ≥3 years of complete follow-up data from the initiation of belimumab (no continuous treatment required). Data for patients with belimumab plus ST treatment (postmarketing registry data, belimumab cohort) will be compared with those for patients with ST only treatment (LUNA data, comparison cohort). Patients who discontinue/initiate belimumab after the start of the follow-up may be included in the comparison/belimumab cohort, respectively. The primary endpoint will be the occurrence of renal flares, for which belimumab's effectiveness will be estimated using a marginal structural model to consider time-dependent treatment and confounding factors. Secondary endpoints will include change in corticosteroid dose, renal disease activity, extrarenal disease activity, disease severity/activity biomarkers, LN class changes, end-stage kidney disease events and hospitalisations., Ethics and Dissemination: This study will be conducted according to the Declaration of Helsinki and the local ethical guidelines. Findings will be submitted to peer-reviewed journals and presented at scientific meetings., Competing Interests: Competing interests: KS received speaker and consulting fees from GSK K.K. and a research grant from Pfizer. NK received a consulting fee from GSK K.K. HN received a consulting fee from GSK K.K. and personal fees from Boehringer Ingelheim, Kyowa Kirin, Toyota Motor Corporation, GSK, Ono Pharmaceutical, Sony and Terumo outside the submitted work. TM, HQ, RAL, ARJL and KG are employees of GSK and hold stocks and shares in the company. NY received a speaker’s fee from Pfizer., (© 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.)

Objective: It is still unclear how glucocorticoids (GCs) affect the long-term clinical course of patients with SLE. The objective of this study is to explore the factors associated with GC-free treatment status., Methods: Using data from the lupus registry of nationwide institutions, GC dose at registration was compared between short, middle and long disease durations of <5, 5-20 and ≥20 years, respectively. After excluding patients who never used GC, we evaluated the relationship between GC-free status and chronic damage using Systemic Lupus International Collaborating Clinics Damage Index., Results: GC doses at enrolment of the 1019 patients were as follows: GC-free in 101 (10%); 0

Background: Infection is a major cause of mortality in patients with systemic lupus erythematosus (SLE). Therefore, minimizing the risk of infection is an important clinical goal to improve the long-term prognosis of SLE patients. Treatment with ≥7.5 mg prednisolone (PSL) or equivalent has been reported to increase the risk of infections. However, it remains unclear whether <7.5 mg PSL or equivalent dose affects the risk of infection in SLE patients. This study evaluated the association between the occurrence of infection in patients with SLE and low-dose glucocorticoid (GC) usage, especially <7.5 mg PSL or equivalent, to explore the GC dose that could reduce infection occurrence., Methods: This prospective cohort study included patients from the Japanese multicenter registry of patients with SLE (defined as ≥4 American College of Rheumatology 1997 revised criteria) over 20 years of age. The PSL dose was categorized as PSL 0-2.5, 2.6-5.0, 5.1-7.5, and 7.6-15.0 mg. The primary outcome was infection requiring hospitalization. We conducted a multivariable analysis using time-dependent Cox regression analysis to assess the hazard ratio of infection occurrence compared with a dose of 0-2.5 mg PSL or equivalent in the other three PSL dose groups. Based on previous reports and clinical importance, the covariates selected were age, sex, and concurrent use of immunosuppressants with GC. In addition, two sensitivity analyses were conducted., Results: The mean age of the 509 SLE patients was 46.7 years; 89.0% were female, and 77.2% used multiple immunosuppressants concomitantly. During the observation period, 52 infections requiring hospitalization occurred. The incidence of infection with a PSL dose of 5.0-7.5 mg was significantly higher than that in the PSL 0-2.5 mg group (adjusted hazard ratio: 6.80, 95% confidence interval: 2.17-21.27). The results of the two sensitivity analyses were similar., Conclusions: Our results suggested that the use of 5.0-7.5 mg PSL or equivalent could pose an infection risk in SLE patients. This finding indicates that PSL dose should be reduced to as low as possible in SLE patients to avoid infection., (© 2022. The Author(s).)

Background: Although vitamin D concentration is reportedly associated with the pathogenesis and pathology of systemic lupus erythematosus (SLE), benefits of vitamin D supplementation in SLE patients have not been elucidated, to our knowledge. We investigated the clinical impacts of vitamin D supplementation in SLE., Methods: A cross-sectional analysis was performed using data from a lupus registry of nationwide institutions. We evaluated vitamin D supplementation status associated with disease-related Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) as a parameter of long-term disease activity control., Results: Of the enrolled 870 patients (mean age: 45 years, mean disease duration: 153 months), 426 (49%) received vitamin D supplementation. Patients with vitamin D supplementation were younger (43.2 vs 47.5 years, P < 0.0001), received higher doses of prednisolone (7.6 vs 6.8 mg/day, P = 0.002), and showed higher estimated glomerular filtration rates (79.3 vs 75.3 mL/min/1.73m2, P = 0.02) than those without supplementation. Disease-related SDI (0.73 ± 1.12 vs 0.73 ± 1.10, P = 0.75), total SDI, and SLE Disease Activity Index (SLEDAI) did not significantly differ between patients receiving and not receiving vitamin D supplementation. Even after excluding 136 patients who were highly recommended vitamin D supplementation (with age ≥ 75 years, history of bone fracture or avascular necrosis, denosumab use, and end-stage renal failure), disease-related SDI, total SDI, and SLEDAI did not significantly differ between the two groups., Conclusions: Even with a possible Vitamin D deficiency and a high risk of bone fractures in SLE patients, only half of our cohort received its supplementation. The effect of vitamin D supplementation for disease activity control was not observed., Competing Interests: The authors have declared that no competing interests exist.

Objective: This study aimed to assess the prevalence and actual treatment conditions for hypertension and dyslipidaemia complicated with systemic lupus erythematosus (SLE)., Methods: This was a cross-sectional study. We established the lupus registry of nationwide institutions (LUNA), a multi-centre cohort of SLE patients in Japan. From February 2016 to July 2018, 597 SLE patients were registered in the LUNA. We evaluated the incidence of hypertension and dyslipidaemia and analysed the risk factors for hypertension and dyslipidaemia by logistic regression analysis., Results: Overall, 597 patients were enrolled in the study. The median age was 44 years, and 88.0% of the patients were female. Among all the patients, 92.9% used prednisolone. The prevalence of hypertension and dyslipidaemia was 43.9% and 54.7%, respectively. Among the patients receiving medication for hypertension, 24.7% exhibited insufficient control (systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg), and among those receiving medication for hyperlipidaemia, 48.1% showed insufficient control (low-density lipoprotein cholesterol >140 mg/dL or triglyceride >150 mg/dL). The risk factors for hypertension were age, body mass index (BMI), disease duration, past maximum dose of prednisolone, and renal involvement, whereas those for dyslipidaemia were age and BMI., Conclusion: About half of the patients had hypertension or dyslipidaemia, and a considerable number of cases were poorly controlled despite medication. Our data suggest that physicians should treat SLE activity as well as its complications, especially the common risk factors for atherosclerosis.

Background: While survival of systemic lupus erythematosus (SLE) patients has improved substantially, problems remain in the management of their emotional health. Medium to high-dose glucocorticoid doses are known to worsen emotional health; the effect is unclear among patients receiving relatively low-dose glucocorticoids. This study aims to investigate the association between low glucocorticoid doses and emotional health in lupus low disease activity state (LLDAS)., Methods: This cross-sectional study drew on data from SLE patients in 10 Japanese institutions. The participants were adult patients with SLE duration of ≥ 1 year who met LLDAS criteria at the study visit from April 2018 through September 2019. The exposure was the daily glucocorticoid dose (mg oral prednisolone). The outcome was the emotional health score of the lupus patient-reported outcome scale (range: 0 to 100). Multiple linear regression analysis was performed with adjustment for confounders including disease-related damage, activity, and psychotropic drug use., Results: Of 192 patients enrolled, 175 were included in the analysis. Their characteristics were as follows: female, 89.7%; median age, 47 years (interquartile range (IQR): 37.0, 61.0). Median glucocorticoid dose was 4.0 mg (IQR 2.0, 5.0), and median emotional health score 79.2 (IQR 58.3, 91.7). Multiple linear regression analysis showed daily glucocorticoid doses to be associated with worse emotional health (β coefficient = - 2.54 [95% confidence interval - 4.48 to - 0.60], P = 0.01)., Conclusions: Daily glucocorticoid doses were inversely associated with emotional health among SLE patients in LLDAS. Further studies are needed to determine whether glucocorticoid tapering leads to clinically significant improvements in emotional health.

Chronic damage accumulation affects not only mortality but also quality of life in patients with systemic lupus erythematosus (SLE). Risk factors for chronic damage were explored in SLE through different onset eras. Two hundred forty-five patients at Okayama University Hospital and Showa University Hospital were divided into three groups based on the onset era: a past-onset group (onset before 1995; n=83), middle-onset group (1996-2009; n=88), and recent-onset group (after 2010; n=74). The mean Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score as an index of chronic damage was 1.93, 1.24, and 0.53 in the past-, middle-, and recent-onset groups, respectively. In the pastonset group, the total SDI score was significantly associated with glucocorticoid monotherapy by linear regression analysis (β-coefficient [β]=0.63; 95% confidence interval [CI], 0.21-1.05) and C-reactive protein levels (β=0.67; 95% CI, 0.27-1.07). In the middle-onset group, the total SDI score was significantly associated with the SLE Disease Activity Index at registration (β=0.09; 95% CI, 0.03-0.12). Reducing the accumulation of chronic damage in SLE patients might be possible with the concomitant use of immunosuppressants and tight control of disease activity., Competing Interests: No potential conflict of interest relevant to this article was reported.

Objective: Quality indicators (QIs) are tools that standardize evaluations in terms of the minimum acceptable quality of care, presumably contributing for the better management of patients with systemic lupus erythematosus (SLE). This study aimed to develop QIs for SLE using electronic health data. Methods: The modified RAND/UCLA Appropriateness Method was used to develop the QIs. First, a literature review was conducted. Second, the candidate QI items that were available to be evaluated using the electronic health data were extracted. Third, the appropriateness of the items was assessed via rating rounds and panelists' discussions. Results: We found 3621 articles in the initial search. Finally, 34 studies were reviewed, from which 17 potential indicators were extracted as candidate QIs. Twelve indicators were selected as the final QI set through the process of appropriateness. The median appropriateness of these 12 indicators was at least 7.5, and all of them were without disagreement. The QI included assessment of disease activity, treatment of SLE, drug toxicity monitoring, treatment of glucocorticoid complications, and assessment of SLE complications. Conclusion: We formulated 12 QIs for the assessment of patients with SLE based on electronic medical data. Our QI set would be a practical tool as a quality measure.

Objective: The objective of this study was to evaluate the chronic damage associated with pregnancies before and after the diagnosis of systemic lupus erythematosus (SLE)., Methods: Using childbearing-aged female SLE patient data registered at the Okayama and Showa University Hospitals, a nested case-control analysis was performed to investigate the relationship between pregnancy and chronic damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)., Results: Pregnancy occurred in 22 patients before and 13 patients after the diagnosis of SLE in 104 eligible patients. Live births occurred in 82% (33/40) and 50% (9/18) of the pregnancies before and after the diagnosis of SLE, respectively. After matching age and disease duration, 33 case patients with chronic damage (SDI ≥ 1) and 33 control patients without chronic damage (SDI = 0) were selected. Hypertension was more frequent in cases than in controls (48% vs. 24%, p  = 0.041). Pregnancies before and after the diagnosis of SLE were comparable between cases and controls (before the diagnosis: nine case patients and eight control patients; after the diagnosis: three case patients and five control patients; p  = 1.00). Even after adjusting for hypertension using multivariate analysis, the pregnancies before and after the diagnosis were not significant predictors for chronic damage (odds ratio = 1.48 (95% confidence interval 0.33-6.65)), p  = 0.60 of the pregnancy before the diagnosis; odds ratio = 0.78 (95% confidence interval 0.13-4.74), p  = 0.78 of the pregnancy after the diagnosis)., Conclusion: Pregnancies, either before or after the diagnosis of SLE, did not show any differences in chronic damage. Our results help alleviate fears regarding childbearing in female patients with SLE and their families.

Objective: Cardiovascular disease is an important contributor to the mortality rate of patients with systemic lupus erythematosus (SLE), which is related to SLE disease activity. Fragmented QRS (fQRS) complexes, defined by additional spikes in the QRS complex, are useful for identifying myocardial scars on electrocardiography and can be an independent predictor of cardiac events. We aimed to assess the relationship between disease activity in patients with SLE and fQRS at the time of diagnosis., Methods: Forty-four patients with SLE were included. Patients with cardiac diseases, other rheumatic diseases, and prior treatment at the time of electrocardiography measurement were excluded. The appearance of fQRS represented exposure. The primary outcome was SLE Disease Activity Index 2000 (SLEDAI-2K). Multiple regression analysis was conducted to assess the association between fQRS and SLEDAI-2K adjusted for age, sex, and time from the estimated onset date to the date of diagnosis., Results: Among patients with SLE at diagnosis, 26 (59.1%) had fQRS. The median SLEDAI-2K was 18 (interquartile range [IQR], 12-22) and 9 (IQR, 8-15) in the fQRS(+) and fQRS(-) groups, respectively. SLEDAI-2K was significantly higher in the fQRS(+) group than in the fQRS(-) group (regression coefficient, 2.69; 95% confidence interval, 0.76-4.61; p = 0.008)., Conclusion: Our results suggested that fQRS(+) patients with SLE had high disease activity. fQRS could likely detect subclinical myocardial involvement in patients with SLE and predict long-term occurrence of cardiac events., Competing Interests: Hiroshi Morita is affiliated with the endowment department of Japan Medtronic, Inc. The other authors declare that there is no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ damage and neuropsychiatric complications (NPSLE) associated with increased morbidity and mortality. The pathogenesis of NPSLE is not yet fully understood, but focal symptoms are thought to most likely result from vascular lesions, whereas diffuse manifestations are more likely related to autoantibody- or cytokine-mediated impairment of neuronal function. Recent progress also has provided evidence that levels of several cytokines/chemokines are upregulated in the central nervous systems of NPSLE patients during active disease and downregulated by treatment. In particular, chemokines appear to play significant roles in both inflammatory and immunological processes in the brain. For instance, we recently showed that levels of the soluble form of the chemokine CX3CL1 are elevated in the cerebrospinal fluid of patients with active NPSLE. In this review, we will discuss the involvement of chemokines in the pathogenesis of NPSLE and their significance as a useful laboratory parameter indicative of active neuropsychiatric disease.

Objective: To determine levels of the soluble form of the chemokine fractalkine (sFkn) and its receptor, CX(3)CR1, in patients with systemic lupus erythematosus (SLE) with neuropsychiatric involvement (NPSLE) and in SLE patients without neuropsychiatric involvement, and to assess their relationship with disease activity and organ damage., Methods: Levels of sFkn in serum and cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Expression of Fkn and CX(3)CR1 was quantified using real-time polymerase chain reaction. Surface expression of CX(3)CR1 on peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry. Disease activity and organ damage were assessed using the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, respectively., Results: Serum sFkn levels were significantly higher in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls. In addition, significant correlations between serum sFkn levels and the SLEDAI, the SLICC/ACR Damage Index, anti-double-stranded DNA and anti-Sm antibody titers, immune complex levels (C1q), and serum complement levels (CH50) were observed. Expression of CX(3)CR1 was significantly greater in PBMCs from patients with active SLE than in those from RA patients or healthy controls. Levels of sFkn were also significantly higher in CSF from untreated patients with newly diagnosed NPSLE than in SLE patients without neuropsychiatric involvement; treatment reduced both serum and CSF levels of sFkn in patients with SLE., Conclusion: Soluble Fkn and CX(3)CR1 may play key roles in the pathogenesis of SLE, including the neuropsychiatric involvement. Soluble Fkn is also a serologic marker of disease activity and organ damage in patients with SLE, and its measurement in CSF may be useful for the diagnosis of NPSLE and followup of patients with NPSLE.