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The article presents a study which evaluates the side-effects of cyclophosphamide (CYC) on menstruation and pregnancy of women with severe rheumatologic disease. The study uses a case-series study of 43 women diagnosed with systemic lupus erythematosus (SLE), vasculitis, and scleroderma before they reached the age of 35. Results show that more women with prior CYC exposure have resulted to elective termination, miscarriage, or preterm birth.

Objective: The Type 1 and 2 systemic lupus erythematosus (SLE) Model was developed to encapsulate all signs and symptoms that patients with SLE experience. Our previous qualitative work demonstrated the model accurately reflects the lived experience of people living with SLE. The objective of this study was to present the Type 1 and 2 SLE Model to rheumatologists to understand how the model fits with their experiences treating patients with SLE., Methods: We conducted a qualitative descriptive study using semistructured interviews with rheumatologists. Rheumatologists were asked about their general impression of the Type 1 and 2 SLE Model, how the model does or does not fit within their approach to treating patients with SLE, the utility of the model in clinical practice, and any suggested changes. Applied thematic analysis identified salient themes., Results: We interviewed 13 rheumatologists. The majority of rheumatologists approved of the model and found it useful to guide therapy and clinical decision-making. Several rheumatologists thought the model was helpful for patient education to manage expectations about differences between Type 1 and Type 2 symptoms and treatments. A few rheumatologists expressed concern that the model could lead to an overdiagnosis of SLE., Conclusion: The Type 1 and 2 SLE Model was accepted by most rheumatologists interviewed and welcomed as a useful approach to identifying and treating symptoms in patients with SLE. Future studies will determine how implementing the Type 1 and 2 SLE Model affects patient understanding, the physician-patient relationship, and clinical outcomes., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Medication nonadherence in systemic lupus erythematosus (SLE) leads to poor clinical outcomes. We developed a clinician-led adherence intervention that involves reviewing real-time pharmacy refill data and using effective communication to address nonadherence. Prior pilot testing showed promising effects on medication adherence. Here, we describe further evaluation of how clinicians implemented the intervention and identify areas for improvement., Methods: We audio recorded encounters of clinicians with patients who were nonadherent (90-day proportion of days covered [PDC] < 80% for SLE medications). We coded recordings for intervention components performed, communication quality, and time spent discussing adherence. We also conducted semistructured interviews with patients and clinicians on their experiences and suggestions for improving the intervention. We assessed change in 90-day PDC post intervention., Results: We included 25 encounters with patients (median age 39, 100% female, 72% Black) delivered by 6 clinicians. Clinicians performed most intervention components consistently and exhibited excellent communication, as coded by objective coders. Adherence discussions took an average of 3.8 minutes, and 44% of patients had ≥ 20% increase in PDC post intervention. In structured interviews, many patients felt heard and valued and described being more honest about nonadherence and more motivated to take SLE medications. Patients emphasized patient-clinician communication and financial and logistical assistance as areas for improvement. Some clinicians wanted additional resources and training to improve adherence conversations., Conclusion: We provide further evidence to support the feasibility, acceptability, and fidelity of the adherence intervention. Future work will optimize clinician training and evaluate the intervention's effectiveness in a large, randomized trial., (Copyright © 2024 by the Journal of Rheumatology.)

Objective: Systemic lupus erythematosus (SLE) flares are associated with increased damage and decreased health-related quality of life. We hypothesized that there is discordance between physicians' and patients' views of SLE flare. In this study, we aimed to explore patient and physician descriptions of SLE flares., Methods: We conducted a qualitative descriptive study using in-depth interviews with a purposeful sample of patients with SLE (who met 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria) and practicing rheumatologists. Interviews were audio-recorded, transcribed, and analyzed using applied thematic analysis., Results: Forty-two patient participants with SLE, representing a range of SLE activity, completed interviews. The majority described flare symptoms as joint pain, fatigue, and skin issues lasting several days. Few included objective signs or laboratory measures, when available, as features of flare. We interviewed 13 rheumatologists from 10 academic and 3 community settings. The majority defined flare as increased or worsening SLE disease activity, with slightly more than half requiring objective findings. Around half of the rheumatologists included fatigue, pain, or other patient-reported symptoms., Conclusion: Patients and physicians described flare differently. Participants with SLE perceived flares as several days of fatigue, pain, and skin issues. Providers defined flares as periods of increased clinical SLE activity. Our findings suggest the current definition of flare may be insufficient to integrate both perceptions. Further study is needed to understand the pathophysiology of patient flares and the best way to incorporate patients' perspectives into clinical assessments., (Copyright © 2024 by the Journal of Rheumatology.)

Background: Type 2 systemic lupus erythematosus (SLE) symptoms, including fatigue, fibromyalgia, and brain fog, contribute to poor health-related quality of life (HRQoL) in patients with lupus. To test the hypothesis that Type 1 (classical inflammatory lupus) activity is associated with Type 2 SLE activity, we characterized the features of Type 2 SLE in patients with a range of lupus nephritis (LN) activity., Methods: This was a cross-sectional study of SLE patients [American College of Rheumatology (ACR) 1997 or Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria] from June 2018 to March 2020. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and the Polysymptomatic Distress Scale. Patients were divided into groups based on their renal status. Active nephritis was defined using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) lupus nephritis parameter. Differences across groups were analyzed by Fisher's exact test and ANOVA., Results: In this cohort of 244 patients (93% female, mean age 43 years, 58% Black), 10% had active nephritis, 35% had historical nephritis, and 55% never had nephritis (non-nephritis). Active nephritis and non-nephritis patients had a similar burden of Type 2 SLE symptoms, despite a difference in Type 1 SLE activity. Patients with active nephritis had higher Type 2 PGA (Physician Global Assessment) scores and reported more Type 2 SLE symptoms than inactive nephritis patients. Patients with inactive nephritis had the lowest Type 2 SLE activity., Conclusions: While Type 2 SLE symptoms are common in SLE, our findings suggest that patients with active nephritis experience significant Type 2 SLE symptoms that may be ameliorated as nephritis improves. We also observed that non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. Therefore, the etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors. Key Points • Patients with active nephritis experienced significant Type 2 symptoms that may be ameliorated as nephritis improves. • Non-nephritis patients had a similar burden of Type 2 SLE symptoms as patients with active nephritis, despite having on average lower Type 1 SLE activity. • Because etiology of Type 2 SLE symptoms is likely multifactorial and may be driven by inflammatory and non-inflammatory biopsychosocial factors., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: In the new Type 1 & 2 model for systemic lupus erythematosus (SLE), Type 1 SLE represents classic inflammatory manifestations, such as arthritis, while Type 2 SLE encompasses symptoms such as pain and fatigue where the relationship to inflammation is less clear. The objective of this study was to interview individuals living with SLE to determine the content and face validity of the Type 1 & 2 SLE model., Methods: We conducted a qualitative study using semi-structured interviews with a purposeful sample of participants who met classification criteria for SLE. Participants were asked to describe their experiences with Type 1 & 2 SLE symptoms and treatments, and they indicated if and how their personal experiences aligned with the Type 1 & 2 SLE model. All interviews were audio-recorded and transcribed; applied thematic analysis identified the most frequent and salient themes., Results: We interviewed 42 participants with SLE. Type 2 SLE symptoms, such as pain and fatigue, were very common, with almost all participants experiencing some Type 2 symptoms at some point during their disease course. Participants described Type 1 SLE symptoms as being acute flares and life-threatening and Type 2 SLE symptoms as "everyday lupus" that affected their daily lives and were a dominant part of their SLE disease experience. Most participants stated they want their rheumatologists to discuss Type 2 symptoms during clinical appointments in order to address their full symptom experience., Conclusion: We demonstrated content and face validity of the Type 1 & 2 SLE model with people living with SLE. Participants in our study largely understood the model and felt it accurately reflected their experience living with SLE. Type 2 SLE symptoms are very common in individuals with SLE and impact patients' quality of life. Using the model to address Type 2 SLE symptoms allows the rheumatologist to incorporate the patient's perspective and provide patient-centered care., Competing Interests: Declaration of conflicting interestsAME has received grant support from Pfizer, Exagen, Immunovant, and GlaxoSmithKline and consulting fees from Amgen. MEBC has received grant support from Pfizer, Exagen, Immunovant, GlaxoSmithKline, and Astra-Zeneca and consulting fees from GlaxoSmithKline, Amgen, and UCB. DSP has received grant support from Immunovant and Exagen; consulting fees from Immunovant and GlaxoSmithKline; and served on a Data Safety Monitor Board for Bristol Myers Squibb. MM has received consulting fees from AstraZeneca. JLR has received grant support from Pfizer, Exagen, Immunovant, Astra-Zeneca and consulting fees from GlaxoSmithKline, Amgen, Aurinia, Immunovant, Janssen, Eli Lily, and Ampel Biosolutions. All other authors have no conflicts of interest to disclose.

Objective: Systemic lupus erythematosus (SLE) disproportionately affects patients from racial and ethnic minority groups. Medication adherence is lower among these patient populations, and nonadherence is associated with worse health outcomes. We aimed to identify factors that enable adherence to immunosuppressive medications among patients with SLE from racial and ethnic minority groups., Methods: Using a qualitative descriptive study design, we conducted in-depth interviews with purposefully selected (1) patients with SLE from racial and ethnic minority groups who were taking immunosuppressants and (2) lupus providers and staff. We focused on adherence facilitators, asking patients to describe approaches supporting adherence and for overcoming common adherence challenges and providers and staff to describe actions they can take to foster patient adherence. We used applied thematic analysis and categorized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model., Results: We interviewed 12 patients (4 adherent and 8 nonadherent based on medication possession ratio) and 12 providers and staff. Although each patient described a unique set of facilitators, patients most often described social support, physical well-being, reminders, and ability to acquire medications as facilitators. Providers also commonly mentioned reminders and easy medication access as facilitators as well as patient education/communication and empowerment., Conclusion: Using an established behavioral change model, we categorized a breadth of adherence facilitators within each domain of the COM-B model while highlighting patients' individual approaches. Our findings suggest that an optimal adherence intervention may require a multi-modal and individually tailored approach including components from each behavioral domain-ensuring medication access (Capability) and utilizing reminders and social support (Opportunity), while coupled with internal motivation through improved communication and empowerment (Motivation)., 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: To account for heterogeneity in systemic lupus erythematosus (SLE) and bridge discrepancies between patient- and physician-perceived SLE activity, we developed the Type 1 and 2 SLE model. We examined PROMIS-29 scores, a composite patient-reported outcome (PRO) measure, through the lens of the model., Methods: Patients completed PROMIS-29 and the polysymptomatic distress scale (PSD). Rheumatologists completed the SLE disease activity index (SLEDAI), and physician's global assessments (PGAs) for Type 1 and 2 SLE. We defined Type 1 SLE using SLEDAI, Type 1 PGA, and active nephritis, and Type 2 SLE using PSD and Type 2 PGA. We compared PROMIS-29 T-scores among Type 1 and 2 SLE groups and explored whether PROMIS-29 can predict Type 1 and 2 SLE activity., Results: Compared to the general population, patients with isolated Type 1 SLE reported greater pain and physical dysfunction but less depression and improved social functions; patients with high Type 2 SLE (irrespective of Type 1 activity) reported high levels of pain, fatigue, and social and physical limitations. Patients with minimal Type 1 and 2 SLE had less depression and greater physical functioning with other domains similar to national norms. PROMIS-29 predicted Type 2 but not Type 1 SLE activity., Conclusion: PROMIS-29 similarities in patients with high Type 2 SLE, with and without active Type 1 SLE, demonstrate the challenges of using PROs to assess SLE inflammation. In conjunction with the Type 1 and 2 SLE model, however, PROMIS-29 identified distinct symptom patterns, suggesting that the model may help clinicians interpret PROs., (© 2023. The Author(s).)

Objective: Manifestations of SLE can be categorised as type 1 (classic signs and symptoms of SLE) or type 2 (fatigue, widespread pain and brain fog with an unclear relationship to inflammation). While measures of type 1 SLE activity exist, most current physician-reported measures do not encompass type 2 SLE manifestations. To better evaluate type 2 SLE symptoms, we developed and psychometrically evaluated a physician-reported measure of type 2 symptoms, the Type 2 Physician Global Assessment ('Type 2 PGA')., Methods and Analysis: The Type 2 PGA was developed and evaluated by six rheumatologists practising in the same academic lupus clinic. The study began with a roundtable discussion to establish consensus guidelines for scoring the Type 2 PGA. Following the roundtable, the Type 2 PGA was psychometrically evaluated using data prospectively collected from 263 patients with SLE enrolled in the Duke Lupus Registry., Results: There was strong intra-rater and inter-rater reliability (intraclass correlation coefficient=0.83), indicating the Type 2 PGA scores were consistent within a rheumatologist and across rheumatologists. The Type 2 PGA was correlated with patient-reported symptoms of polysymptomatic distress (r=0.76), fatigue (r=0.68), cognitive dysfunction (r=0.63), waking unrefreshed (r=0.62) and forgetfulness (r=0.60), and weakly correlated with the Type 1 PGA and the Systemic Lupus Erythematosus Disease Activity Index., Conclusion: The Type 2 PGA performed well as a physician-reported measure of type 2 SLE symptoms. The incorporation of the Type 2 PGA into a routine rheumatology visit may improve patient care by bringing the provider's attention to certain symptoms not well represented in conventional measures of disease activity., Competing Interests: Competing interests: MEBC has received grant support from AstraZeneca, Pfizer, Exagen and Immunovant. JLR has received grant support from Pfizer, Exagen and Immunovant, and consulting fees from Aurinia, Immunovant, Janssen, Eli Lilly, Ampel Biosolutions, GlaxoSmithKline and Amgen. TC has received grant support from Merck and consulting fees from Regenxbio. DSP has received grant support from Immunovant and Exagen, consulting fees from Immunovant and GlaxoSmithKline, and served on a Data Safety Monitor Board for Bristol Myers Squibb. MM has received consulting fees from AstraZeneca. AME has received grant support from Pfizer, Exagen and Immunovant, and consulting fees from Amgen., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Objective: With the onset of the COVID-19 pandemic, an annual multi-institutional face-to-face rheumatology objective structured clinical examination (ROSCE) was transformed into a virtual format. The educational goals of the virtual ROSCE (vROSCE) were to reproduce the educational value of the previous in-person ROSCE, providing a valuable formative assessment of rheumatology training activities encompassing the 6 Accreditation Council for Graduate Medical Education (ACGME) core competencies for fellows-in-training (FITs). This article describes the novel design, feasibility, and stakeholder value of a vROSCE., Methods: Through an established collaboration of 5 rheumatology fellowship training programs, in February 2021, a vROSCE was created and conducted using a Zoom platform. Station development included learning objectives, FIT instructions, faculty proctor instructions, and a checklist by which to provide structured formative feedback. An anonymous, optional web-based survey was sent to FIT participants to evaluate the experience., Results: Twenty-three rheumatology FITs from 5 institutions successfully rotated through 6 stations in the vROSCE. Immediate feedback was given to each FIT using standardized rubrics structured around ACGME core competencies. A total of 65% of FITs (15 of 23) responded to the survey, and 93% of survey respondents agreed or strongly agreed that the vROSCE was a helpful educational activity and identified individualized opportunities for improvement., Conclusion: A vROSCE is an innovative, feasible, valuable, and well-received educational technology tool. The vROSCE enriched rheumatology FITs' education and offered collaborative learning experiences across institutions., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Despite high rates of medication nonadherence among patients with systemic lupus erythematosus (SLE), effective interventions to improve adherence in SLE are limited. We aimed to assess the feasibility of a pilot intervention and explore its effect on adherence., Methods: The intervention used pharmacy refill data to monitor nonadherence and prompt discussions surrounding SLE medications during clinic encounters. Over 12 weeks, the intervention was delivered through routine clinic visits by providers to patients with SLE who take SLE-specific medications. We measured acceptability, appropriateness, and feasibility using provider surveys. We also measured acceptability by patient surveys and feasibility by medical record documentation. We explored change in adherence by comparing percent of patients with medication possession ratio (MPR) ≥80% 3 months before and after the intervention visit using the McNemar's test., Results: Six rheumatologists participated; 130 patients were included in the analysis (median age 43, 95% female, and 59% racial and ethnic minorities). Implementation of the intervention was documented in 89% of clinic notes. Provider surveys showed high scores for feasibility (4.7/5), acceptability (4.4/5), and appropriateness (4.6/5). Among patient surveys, the most common reactions to the intervention visit were feeling determined (32%), empowered (32%), and proud (19%). Proportion of patients with MPR ≥80% increased from 48% to 58% (P = 0.03) after the intervention visit., Conclusion: Our intervention showed feasibility, acceptability, and appropriateness and led to a statistically significant improvement in adherence. Future work should refine the intervention, assess its efficacy in a controlled setting, and adapt its use among other clinic settings., (© 2021 American College of Rheumatology.)

Objective: Medication nonadherence is common among patients with systemic lupus erythematosus (SLE), and adherence often fluctuates with time. Underrepresented racial minorities have disproportionately lower rates of medication adherence and more severe SLE manifestations. We aimed to identify modifiable factors associated with persistent medication nonadherence., Methods: Patients taking ≥1 SLE medication were enrolled. Adherence data were obtained at baseline and at follow-up roughly 1 year later using both self-reported adherence and pharmacy refill data. Covariates included patient-provider interaction, patient self-efficacy, and clinical factors. We compared characteristics of patients in 3 groups using the Kruskal-Wallis H test: persistent nonadherence (low adherence by self-report and refill rates at both time points); persistent adherence (high adherence by self-report and refill rates at both time points); and inconsistent adherence (the remainder)., Results: Among 77 patients (median age 44 years, 53% Black, 96% female), 48% had persistent nonadherence. Compared with other adherence groups, patients with persistent nonadherence were younger and more likely to be Black, have lower income, take ≥2 SLE medications, have higher SLE-related damage at baseline, and have higher physician global assessment of disease activity at follow-up. Persistently nonadherent patients also rated more hurried communication with providers (particularly fast speech and difficult word choice) and had lower self-efficacy in managing medications., Conclusion: Potential avenues to improve medication adherence include optimizing patient-provider communication, specifically avoiding difficult vocabulary and fast speech, and enhancing patient self-efficacy, particularly among younger Black patients with lower income who are at higher risk for nonadherence., (© 2022 American College of Rheumatology.)

Objective: Medication nonadherence is common in patients with systemic lupus erythematosus (SLE) and negatively affects outcomes. To better recognize and address nonadherence in this population, there is a need for an easily implementable tool with interpretable scores. Domains of Subjective Extent of Nonadherence (DOSE-Nonadherence) is a measure that captures both extent of and reasons for nonadherence. We refined and evaluated DOSE-Nonadherence for patients with SLE., Methods: We refined the reasons for the nonadherence domain of DOSE-Nonadherence through rheumatologist feedback and patient cognitive interviewing. We then administered the refined instrument to patients prescribed oral SLE medications and compared the results to the Beliefs About Medicines Questionnaire (BMQ), the Medication Adherence Self-Report Inventory (MASRI), medication possession ratios (MPRs), and hydroxychloroquine (HCQ) blood levels using Pearson correlations., Results: Five rheumatologists provided feedback; 16 patients (median age 43 yrs, 100% female, 50% Black) participated in cognitive interviews and 128 (median age 49 yrs, 95% female, 49% Black, 88% on antimalarials, and 59% on immunosuppressants) completed the refined instrument. Items assessing extent of nonadherence produced reliable scores (α 0.89) and identified 47% as nonadherent. They showed convergent validity with MASRI (r = -0.57), HCQ blood levels (r = -0.55), to a lesser extent MPRs (r = -0.34 to -0.40), and discriminant validity with BMQ domains (r = -0.27 to 0.32). Nonadherent patients reported on average 3.5 adherence barriers, the most common being busyness/forgetting (62%), physical fatigue (38%), and pill fatigue (33%)., Conclusion: Our results support the reliability and validity of DOSE-Nonadherence for SLE medications. This refined instrument, DOSE-Nonadherence-SLE, can be used to identify, rigorously study, and guide adherence intervention development in SLE., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: Underrepresented racial and ethnic minorities are disproportionately affected by systemic lupus erythematosus (SLE). Racial and ethnic minorities also have more severe SLE manifestations that require use of immunosuppressive medications, and often have lower rates of medication adherence. We aimed to explore barriers of adherence to SLE immunosuppressive medications among minority SLE patients., Methods: We conducted a qualitative descriptive study using in-depth interviews with a purposive sample of racial minority SLE patients taking oral immunosuppressants (methotrexate, azathioprine, or mycophenolate), and lupus clinic providers and staff. Interviews were audiorecorded, transcribed, and analyzed using applied thematic analysis. We grouped themes using the Capability, Opportunity, Motivation, Behavior conceptual model., Results: We interviewed 12 SLE patients (4 adherent, 8 nonadherent) and 12 providers and staff. We identified capability barriers to include external factors related to acquiring medications, specifically cost-, pharmacy-, and clinic-related issues; opportunity barriers to include external barriers to taking medications, specifically logistic- and medication-related issues; and motivation factors to include intrinsic barriers, encompassing patients' knowledge, beliefs, attitudes, and physical and mental health. The most frequently described barriers were cost, side effects, busyness/forgetting, and lack of understanding, although barriers differed by patient and adherence level, with logistic and intrinsic barriers described predominantly by nonadherent patients and side effects described predominantly by adherent patients., Conclusion: Our findings suggest that interventions may be most impactful if they are designed to facilitate logistics of taking medications and increase patients' motivation while allowing for personalization to address the individual differences in adherence barriers., (© 2021 American College of Rheumatology.)

Objective: We have developed a new conceptual model to characterise the signs and symptoms of SLE: the Type 1 and 2 SLE Model. Within the original model, Type 1 SLE consists of inflammatory manifestations like arthritis, nephritis and rashes; Type 2 SLE includes symptoms of fatigue, myalgia, mood disturbance and cognitive dysfunction. Through in-depth interviews, we explored how the Type 1 and 2 SLE Model fits within the lived experience of patients with SLE, with a focus on the connection between Type 1 and Type 2 SLE symptoms., Methods: Semistructured in-depth interviews were conducted among adult participants meeting 1997 American College of Rheumatology or Systemic Lupus International Collaborating Clinics criteria for SLE. Participants were purposefully selected for age, race, sex and nephritis history. All interviews were audio-recorded and transcribed. Data were analysed through episode profile and thematic analysis., Results: Through interviews with 42 patients with SLE, two patterns of Type 2 SLE emerged: Intermittent (n=18) and Persistent (n=24). Participants with Intermittent Type 2 SLE described feeling generally well when Type 1 is inactive; these participants were younger and had more internal SLE manifestations. Participants with Persistent Type 2 described always experiencing Type 2 symptoms despite inactive Type 1, although the severity may fluctuate. Participants with Persistent Type 2 SLE experienced traditional lupus symptoms of joint pain, hair loss and rash, but less often had severe organ system involvement., Conclusions: By listening to the stories of our patients, we found two underlying patterns of Type 2 SLE: Intermittent Type 2 symptoms that resolve in synchrony with Type 1 inflammatory symptoms, and Persistent Type 2 symptoms that continue despite remission of Type 1 symptoms., Competing Interests: Competing interests: AME reports grant support from Exagen to her institution outside the submitted work. JLR reports grant support from Exagen to her institution outside the submitted work; consulting fees from Eli Lilly, Immunovant and Exagen. AC reports grant support from UCB to her institution outside the submitted work. DSP reports consulting fees from Immunovant and participation on a Data Safety Monitoring Board or Advisory Board for Bristol Myers Squibb. LGC-S reports grant support from GlaxoSmithKline to her institution outside the submitted work; honorarium from Pennsylvania State University and the American College of Rheumatology. JD reports grant support from Pfizer outside the submitted work. MEBC reports grant support from Exagen, UCB and GlaxoSmithKline to her institution outside the submitted work; consulting fees from UCB, AstraZeneca and GlaxoSmithKline outside the submitted work. KM, MM and RES have no relevant competing interests to declare., (© 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: Limited health literacy and numeracy are associated with worse patient-reported outcomes and higher disease activity in systemic lupus erythematosus (SLE), but which factors may mediate this association is unknown. We sought to determine the association of health literacy and numeracy with SLE knowledge., Methods: Patients with SLE were recruited from an academic center clinic. Participants completed validated assessments of health literacy (Newest Vital Sign [NVS]; n = 96) and numeracy (Numeracy Understanding in Medicine Instrument, Short Version [S-NUMI]; n = 85). They also completed the Lupus Knowledge Assessment Test (LKAT), which consists of 4 questions assessing SLE knowledge that were determined through consensus expert opinion for their wide applicability and importance related to self-management of the disease. Descriptive statistics and multivariable logistic regression modeling were used to analyze the results., Results: In our SLE cohort (n = 125), 33% (32/96) had limited health literacy and 76% (65/85) had limited numeracy. The majority correctly identified that hydroxychloroquine prevented SLE flares (91%); however, only 23% of participants correctly answered a numeracy question assessing which urine protein to creatinine (UPC) ratio was > 1000 mg/g. The mean LKAT score was 2.7 out of 4.0. Limited health literacy, but not numeracy, was associated with lower knowledge about SLE as measured by the LKAT, even after adjusting for education., Conclusion: Patients with SLE with limited health literacy had lower knowledge about SLE. The LKAT could be further refined and/or used as a screening tool to identify patients with knowledge gaps. Further work is needed to improve patients' understanding of proteinuria and investigate whether literacy-sensitive education can improve care., (Copyright © 2022 by the Journal of Rheumatology.)

Objective: We developed a model that categorizes systemic lupus erythematosus (SLE) activity into two dimensions: Type 1 SLE consists of inflammatory activity, including arthritis, nephritis, and rashes; Type 2 SLE includes fatigue, myalgia, mood disturbance, and cognitive dysfunction. Patient-reported outcome (PRO) measures have received attention as a way to capture symptomatology of SLE. The objective of this study was to explore the use of existing PRO measures to classify Type 1 and 2 SLE activity., Methods: Systemic lupus erythematosus patients completed three questionnaires: Systemic Lupus Activity Questionnaire (SLAQ), Polysymptomatic Distress Scale (PSD), and Patient Health Questionnaire (PHQ-2). SLE Disease Activity Index (SLEDAI) and physician global assessments (PGA; 0-3) for Type 1 and Type 2 activity were also recorded. High Type 1 SLE activity was defined as cSLEDAI ≥4 (scored without labs), SLEDAI ≥6, active nephritis, or Type 1 PGA ≥1.0. High Type 2 SLE activity was defined as Type 2 PGA ≥1.0. Patients with both high Type 1 and 2 activity were defined as Mixed SLE, and patients with low Type 1 and 2 activity were defined as Minimal SLE. Data were reduced with a factor analysis. Using a reduced set of 13 variables, multinomial logistic regression models estimated the probability of Minimal, Type 1, Type 2, and Mixed SLE classification., Results: The study included 208 patients with SLE. The model accurately predicted the clinician-based Type 1 and 2 SLE classification in 63% of patients; 73% of patients had their Type 1 SLE activity accurately predicted; and 83% had their Type 2 SLE activity accurately predicted. Performance varied by group: 87% of Minimal patients were correctly predicted to be in the Minimal SLE group, yet only about one-third of patients in the Type 1 group were correctly predicted to be in the Type 1 group., Conclusions: Our findings indicate Type 2 SLE activity can be identified by patient-reported data. The use of PROs was not as accurate at predicting Type 1 activity. These findings highlight the challenges of using PROs to categorize and classify SLE symptoms since some manifestations of Type 1 activity (e.g., nephritis) may be essentially clinically silent while other Type 1 manifestations may cause severe symptoms.

Objective: Despite significant racial disparities in systemic lupus erythematosus (SLE) outcomes, few studies have examined how disparities may be perpetuated in clinical encounters. We aimed to explore associations between areas of clinical encounters - patient-provider communication and patient self-efficacy - with SLE-related damage, in order to identify potential areas for intervention to reduce SLE outcome disparities., Methods: We collected cross-sectional data from a tertiary SLE clinic including patient-provider communication, general self-efficacy, self-efficacy for managing medications and treatments, patient-reported health status, and clinical information. We compared racial groups and used logistic regression to assess race-stratified association of patient-provider communication and patient self-efficacy with having SLE-related damage., Results: Among 121 patients (37% White, 63% African American), African Americans were younger, more likely to be on Medicaid, and less likely to be college educated, married, or living with a partner or spouse. African Americans reported less fatigue and better social function, took more complex SLE medication regimens, had lower fibromyalgia (FM) scores, and had higher SLE disease activity and SLE-related damage scores. African Americans reported similar self-efficacy compared to White patients, but they reported more hurried communication with providers, which was reflected in their perception that providers used words that were difficult to understand. Perceiving providers use difficult words and lower general self-efficacy were associated with having SLE-related damage among African American but not White patients., Conclusion: African Americans had more severe SLE and perceived more hurried communication with providers. Both worse communication and lower self-efficacy were associated with having SLE-related damage among African American but not White patients, suggesting that these factors should be investigated as potential interventions to reduce SLE racial disparities., (Copyright © 2021 by the Journal of Rheumatology.)

We sought to determine if analyzing internal medicine (IM) resident performance on the in-training exam (ITE) might reveal curricular needs in rheumatology education beyond those intuitive to learners and educators from their perceptions and experience. We analyzed ITE scores of post-graduate year (PGY) 2 IM residents at our institution from 2010 to 2017. We sorted rheumatology-related educational objectives on the ITEs into 10 disease categories and calculated average scores. We then surveyed our IM residents' self-reported confidence and rheumatology educators' perceptions of IM resident proficiency in the 10 categories on a 10-point Likert scale. Finally, we tallied diagnoses in each category encountered by IM residents in rheumatology clinic. Pearson's correlation coefficients were calculated for the relationship between these data. The ITEs exposed 402 residents to 63 rheumatology-related educational objectives in the 10 categories; 24 objectives were categorized as "other." Survey respondents included 38 residents and 22 educators. There was no correlation between ITE scores in the 10 categories and resident confidence (r = - 0.226, p = 0.530), educator perception (r = - 0.274, p = 0.445), or diagnoses encountered (r = - 0.310, p = 0.383). There was a strong positive correlation between resident confidence and educator perception (r = 0.934, p < 0.001). ITE performance was low in crystalline arthritis and osteoarthritis despite high resident confidence, educator perception, and number of diagnoses seen. Our analysis of IM resident ITE performance identified curricular gaps not apparent in surveys of learner and educator perceptions or an assessment of learner experience. Key Points • In this study, we demonstrate how a systematic analysis of internal medicine resident performance on the in-training exam can identify important curricular gaps in rheumatology education that are not apparent in assessments of learners and educator perceptions or learner experience in rheumatology clinic. • In-training exam performance was low in crystalline arthritis and osteoarthritis despite high resident confidence, educator perception of proficiency, and number of diagnoses seen in these categories. • When rheumatology curricula for internal medicine residents are developed solely on the basis of learner and educator perceptions, common disorders traditionally considered "easy" may be overlooked.

Objective: The type 1 and type 2 systemic lupus erythematosus (SLE) categorization system was recently proposed to validate the patients' perspective of disease and to capture a more comprehensive spectrum of symptoms. The objective of this study was to characterize the clinical manifestations of SLE subtypes and to determine the correlation between the patient- and physician-reported measures used in the model., Methods: This was a cross-sectional study of patients with SLE in a university clinic. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and 2011 American College of Rheumatology fibromyalgia (FM) criteria. Active SLE was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥6, clinical SLEDAI score ≥4, or active lupus nephritis. We identified 4 groups: type 1 SLE (active SLE without FM), type 2 SLE (inactive SLE with FM), mixed SLE (active SLE with FM), and minimal SLE (inactive SLE without FM)., Results: In this cohort of 212 patients (92% female, mean age 45 years), 30% had type 1 SLE, 8% had type 2 SLE, 13% had mixed SLE, and 49% had minimal SLE. Regardless of SLE disease activity, patients with FM (21%), reported higher SLAQ scores, patient global assessment scores, and self-reported lupus flare that resulted in discordance between patient- and physician-reported measures., Conclusion: Fatigue, widespread pain, sleep dysfunction, and mood disorders are common symptoms in SLE. Identifying these symptoms as type 2 SLE may be a method to improve patient communication and understanding. The level of type 2 SLE impacts patients' perception of disease and self-reported symptoms. The SLAQ may need to be reinterpreted based on the FM severity scale., (© 2020, American College of Rheumatology.)

Objective: Medication nonadherence is more common in African Americans compared with Caucasians. We examined the racial adherence gaps among patients with systemic lupus erythematosus (SLE) and explored factors associated with nonadherence., Methods: Cross-sectional data were obtained from consecutive patients prescribed SLE medications seen at an academic lupus clinic between August 2018 and February 2019. Adherence was measured using both self-report and pharmacy refill data. High composite adherence was defined as having both high self-reported adherence and high refill rates. Covariates were patient-provider interaction, patient-reported health status, and clinical factors. We compared adherence rates by race and used race-stratified analyses to identify factors associated with low composite adherence., Results: Among 121 patients (37% Caucasian, 63% African American), the median age was 44 years (range 22-72), 95% were female, 51% had a college education or more, 46% had private insurance, and 38% had high composite adherence. Those with low composite adherence had higher damage scores, patient-reported disease activity scores, and more acute care visits. High composite adherence rate was lower among African Americans compared with Caucasians (30% vs 51%, P = 0.02), and the gap was largest for those taking mycophenolate (26% vs 75%, P = 0.01). Among African Americans, low composite adherence was associated with perceiving fewer "Compassionate respectful" interactions with providers and worse anxiety and negative affect. In contrast, among Caucasians, low composite adherence was only associated with higher SLE medication regimen burden and fibromyalgia pain score., Conclusion: Significant racial disparities exist in SLE medication adherence, which likely contributes to racial disparities in SLE outcomes. Interventions may be more effective if tailored by race, such as improving patient-provider interaction and mental health among African Americans., (© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To bring recent advances in pregnancy management in lupus to women nationwide, this multidimensional educational intervention sought to equip community rheumatologists with the needed skills, attitudes, and confidence to manage contraceptive decisions and pregnancy planning for women with lupus., Methods: The program included an in-person didactic, training in use of a comprehensive handout to guide contraception and pregnancy conversations, a simulated clinical experience, and access to an innovative website (www.lupuspregnancy.org). The program was analyzed using mixed methods, which included a quantitative survey by e-mail before and after program completion and multiple qualitative interviews about attendees' experiences integrating created resources into practice., Results: The analysis included 68 preintervention surveys and 55 postintervention surveys. For qualitative analysis, eight interviews were completed until thematic saturation was achieved. After completion of the program, there was an increase in providers reporting a systematic approach to preparing a woman with lupus for pregnancy (from 45.6% to 94.6%; P < 0.0001). Confidence in choosing both appropriate contraception and pregnancy-compatible medications improved significantly. As expected, change in knowledge about contraception was limited. Qualitative themes included the utility of the printable handouts, enthusiasm for the program, increased confidence and, importantly, increased empathy for the patients., Conclusion: We created a valuable implementation tool that improves self-reported provider skills and confidence in managing women with lupus who desire pregnancy. Providers now have access to a unique curriculum and resources that encourage providers to have open and accurate conversations about pregnancy, thus creating lasting clinical change., (© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Teratogenic medications are often prescribed to women of childbearing age with autoimmune diseases. Literature suggests that appropriate use of contraception among these women is low, potentially resulting in high-risk unintended pregnancies. Preliminary review in our clinic showed suboptimal documentation of women's contraceptive use. We therefore designed a quality improvement initiative to target three process measures: documentation of contraception usage and type, contraception counselling and provider action after counselling. We reviewed charts of rheumatology clinic female patients aged 18-45 over the course of 10 months; for those who were on teratogenic medications (methotrexate, leflunomide, mycophenolate and cyclophosphamide), we looked for evidence of documentation of contraception use. We executed multiple plan-do-study-act (PDSA) cycles to develop and evaluate interventions, which centred on interprofessional provider education, modification of electronic medical record (EMR) templates, periodic provider reminders, patient screening questionnaires and frequent feedback to providers on performance. Among eligible patients (n=181), the baseline rate of documentation of contraception type was 46%, the rate of counselling was 30% and interventions after counselling occurred in 33% of cases. Averaged intervention data demonstrated increased provider performance in all three domains: documentation of contraception type increased to 64%, counselling to 45% and provider action to 46%. Of the patients with documented contraceptives, 50% used highly effective, 27% used effective and 23% used ineffective contraception methods. During this project, one unintentional pregnancy occurred in a patient on methotrexate not on contraception. Our interventions improved three measures related to contraception counselling and documentation, but there remains a need for ongoing quality improvement efforts in our clinic. This high-risk population requires increased provider engagement to improve contraception compliance, coupled with system-wide EMR changes to increase sustainability., Competing Interests: Competing interests: None declared.

Objective: Infusible disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed in rheumatology and other fields. There are no published formal educational curricula that rheumatology fellowship programs can use to teach infusion reaction management skills to fellows. We aimed to better understand this educational gap and implement and assess the effectiveness of an experiential curriculum on acute infusion reaction management., Methods: We included current rheumatology fellows and recent graduates from 5 fellowship programs. Using a novel behavioral checklist, we assessed fellows' performance managing an infusion reaction in a simulation, followed by a didactic session focused on infusion reactions. Pre- and postsurveys assessed experiences to determine relevance, as well as attitudes and knowledge., Results: Despite ubiquitous prescribing of infusible biologic DMARDs, >50% of fellows were uncomfortable managing infusion reactions. Only 11% of fellows reported infusion reaction training during fellowship, but 56% reported managing actual patient infusion reactions. In the simulated infusion reaction, fellows managed grade-1 reactions appropriately, but grade-4 reactions poorly, meeting <50% of objectives. All fellows discontinued the infusion in the setting of anaphylaxis, but only 56% administered epinephrine. There was no difference in performance or written knowledge by training year. All fellows felt more prepared to manage infusion reactions postcurriculum and were satisfied with the experience., Conclusion: We confirmed an education gap in rheumatology fellowship training regarding infusion reactions, both in knowledge and performance. We developed and implemented a brief experiential curriculum including simulation of a high-risk patient-care scenario. This curriculum was well received and is easily exportable to other programs., (© 2017, American College of Rheumatology.)

Objective: Some sources urge caution when prescribing hydroxychloroquine (HCQ) to patients with G6PDH deficiency, presumably due to a risk of hemolytic anemia. There are limited published data, however, to support this risk. Additionally, not all patients with G6PDH deficiency are at similar risk for hemolysis, and people with the African variant are at particularly low risk. Through a retrospective chart review, we aimed to quantify the frequency of G6PDH-deficient patients with hemolysis attributed to HCQ., Methods: We identified Duke University Medical Center rheumatology patients with HCQ use and a measured G6PDH level. A retrospective chart review was performed, recording demographics, G6PDH levels, episodes of anemia, laboratory values consistent with hemolysis, and HCQ use., Results: Of the 275 patients reviewed, 84% were female; 46% were African American and 48% were white. The leading diagnoses were systemic lupus erythematosus (32%), rheumatoid arthritis (29%), and inflammatory arthritis (14%). Only 4% of patients were G6PDH deficient (all African American). Two G6PDH-deficient patients had hemolysis during severe lupus flares that occurred while not taking HCQ. There were no reported episodes of hemolysis in more than 700 months of HCQ exposure among the 11 G6PDH-deficient patients., Conclusion: This is the largest study to date evaluating G6PDH deficiency with concurrent use of HCQ. Of 11 patients with G6PDH deficiency, 2 had episodes of hemolysis, but these did not occur during HCQ therapy. These data do not support routine measurement of G6PDH levels or withholding HCQ therapy among African American patients with G6PDH deficiency., (© 2017, American College of Rheumatology.)

Objective: Measurement is necessary to gauge improvement. US training programs have not previously used shared standards to assess trainees' mastery of the knowledge, skills, and attitudes necessary to practice rheumatology competently. In 2014, the Accreditation Council for Graduate Medical Education (ACGME) Next Accreditation System began requiring semiannual evaluation of all medicine subspecialty fellows on 23 internal medicine subspecialty reporting milestones. Since these reporting milestones are not subspecialty specific, rheumatology curricular milestones were needed to guide rheumatology fellowship training programs and fellows on the training journey from internist to rheumatologist., Methods: Rheumatology curricular milestones were collaboratively composed by expanding the internal medicine reporting milestones to delineate the specific targets of rheumatology fellowship training within 6 ACGME core competencies. The 2006 American College of Rheumatology core curriculum for rheumatology training programs was updated., Results: A total of 80 rheumatology curricular milestones were created, defining progressive learning through training; most focus on patient care and medical knowledge. The core curriculum update incorporates the new curricular milestones and rheumatology entrustable professional activities., Conclusion: Rheumatology curricular milestones are now available for implementation by rheumatology fellowship training programs, providing a clear roadmap for specific training goals and a guide to track each fellow's achievement over a 2-year training period. The comprehensive core curriculum delineates the essential breadth of knowledge, skills, and attitudes that define rheumatology, and provides a guide for educational activities during fellowship training. These guiding documents are now used to train and assess fellows as they prepare for independent rheumatology practice as the next generation of rheumatologists., (© 2016, American College of Rheumatology.)

Context: Graduate medical trainees have a critical role in the teaching of other trainees. Improving their teaching requires an understanding of their attitudes towards teaching and their motivation to teach. Both have been incompletely explored in this population. We aimed to better understand graduate medical trainees' attitudes towards teaching and motivation to teach in the clinical setting in order to inform modifications to resident-as-teacher (RAT) programmes and enhance teaching practices., Methods: We applied Q methodology, an established sorting method, to identify and quantify the factors that have an impact on trainees' engagement in teaching. We invited house officers at our institution to rank-order 47 statements regarding their attitudes to and motivation for teaching. Respondents explained their Q-sort rankings in writing and completed a demographic questionnaire. By-person factor analysis yielded groups of individuals with similar attitudes., Results: One hundred and seven trainees completed the Q-sort. We found three primary groups of attitudes towards teaching in the clinical setting: enthusiasm, reluctance and rewarded. Enthusiastic teachers are committed and make time to teach. Teaching increases their job satisfaction. Reluctant teachers have enthusiasm but are earlier in training and feel limited by clinical workload and unprepared. Rewarded teachers feel teaching is worthwhile and derive satisfaction from the rewards and recognition they receive for teaching., Conclusions: This improved understanding of common attitudes shared by groups of residents will help curriculum designers create RAT programmes to further reinforce and encourage attitudes that promote teaching as well as improve trainees' motivation to teach. Designing RAT programmes that acknowledge the attitudes to and motivations for teaching should help develop effective teachers to improve educational outcomes. Directed efforts to enhance motivation for reluctant teachers and encourage more positive attitudes in rewarded teachers may lead to improved teaching behaviours among residents., (© 2016 John Wiley & Sons Ltd.)

Objective: Enhancing rheumatology fellows' teaching skills in the setting of inpatient consultation may have a broad positive impact. Such efforts may improve fellows' clinical skills and overall patient care. Most importantly, effective resident-fellow teaching interactions may not only increase residents' knowledge of rheumatology but may influence their career choice. However, a number of barriers to the resident-fellow teaching interaction have been identified, including fellows' teaching skills. We developed the Fellow As Clinical Teacher (FACT) curriculum in order to enhance fellows' teaching skills during inpatient consultation., Methods: The FACT curriculum was delivered in two 45-minute workshops during the 3-day Winter Symposium of the Carolinas Fellows Collaborative. We evaluated its effect with self-assessment surveys and fellow performance on the objective structured teaching exercise (OSTE) before and after participation in the curriculum., Results: Nineteen fellows from 4 rheumatology training programs participated in the pre- and post-curriculum OSTEs and 18 fellows completed pre- and post-curriculum surveys. OSTE scores improved on 5 of the 8 items assessed, and the total OSTE score improved as well (34.7 versus 29.5; P < 0.01) after the FACT curriculum. Fellows' self-assessment of their teaching skills and intent to teach during consultation also increased after participation in the curriculum., Conclusion: The FACT curriculum, focused on teaching during consultation, improved fellows' teaching skills and attitudes toward teaching. Improving and increasing fellow teaching, particularly in the consultation setting, may impact patient care, resident and fellow learning, and teaching skills of future faculty, and could potentially influence residents' career choice., (© 2016, American College of Rheumatology.)

Interested faculty enrolled in this 6-month-long quality improvement (QI) course to facilitate independent QI project work. The course included monthly 1.5-hour sessions: 20-minute presentations covering key QI concepts, then small group activities to facilitate project work. Faculty were required to identify, construct, and implement an independent QI project. They met individually with mentors twice during the course, with additional guidance offered virtually via phone or e-mail, and completed pretests and posttests of QI knowledge (maximum score = 15) and self-assessed confidence. A statistically significant difference in knowledge (pre-course mean = 7.75, standard deviation [SD] = 3.06; post-course mean = 11.75, SD = 3.28; P = .02) and self-assessed confidence (pre mean = 3.08, SD = 0.65; post mean = 4.5, SD = 0.68; P < .0001) was found. Of 8 faculty, 5 were able to conduct small tests of change; 3 studied the current processes and planned to run tests of change. Positive responses to this course helped obtain buy-in from leadership to develop a leadership program in QI., (© The Author(s) 2014.)

Objective: While several regional fellowship groups conduct rheumatology objective structured clinical examinations (ROSCEs), none have been validated for use across programs. We aimed to establish agreement among subspecialty experts regarding checklist items for several ROSCE stations., Methods: We administered a 1-round survey to assess the importance of 173 assessment checklist items for 11 possible ROSCE stations. We e-mailed the survey to 127 rheumatology educators from across the US. Participants rated each item's importance on a 5-point Likert scale (1 = not important to 5 = very important). Consensus for high importance was predefined as a lower bound of the 95% confidence interval ≥4.0., Results: Twenty-five individuals (20%) completed the expert panel survey. A total of 133 of the 173 items (77%) met statistical cutoff for consensus to retain. Several items that had population means of ≥4.0 but did not meet the predetermined definition for consensus were rejected. The percentage of retained items for individual stations ranged from 24% to 100%; all items were retained for core elements of patient counseling and radiograph interpretation tasks. Only 24% of items were retained for a rehabilitation medicine station and 60% for a microscope use/synovial fluid analysis station., Conclusion: This single-round expert panel survey established consensus on 133 items to assess on 11 proposed ROSCE stations. The method used in this study, which can engage a diverse geographic representation and employs rigorous statistical methods to establish checklist content agreement, can be used in any medical field., (© 2015, American College of Rheumatology.)

Objective: Vitamin D modulates the immune response and blocks induction of an interferon (IFN) signature by systemic lupus erythematosus (SLE) sera. This study was undertaken to investigate the effects of vitamin D supplementation on the IFN signature in patients with SLE., Methods: SLE patients (n = 57) with stable, inactive disease, a serum 25-hydroxyvitamin D (25[OH]D) level ≤20 ng/ml, an elevated anti-double-stranded DNA antibody level, and an IFN signature (as determined by measuring the expression levels of 3 IFN response genes) were randomized into a 12-week double-blind, placebo-controlled trial of vitamin D3 at doses of 2,000 IU or 4,000 IU. An IFN signature response was defined as a 50% reduction in the expression of 1 of the 3 genes or a 25% reduction in the expression of 2 of the 3 genes. Disease activity, adverse events, and endocrine effects were assessed., Results: Baseline characteristics of the patients in the 3 treatment groups (placebo, low-dose vitamin D3 , or high-dose vitamin D3 ) were similar. Repletion of 25(OH)D (i.e., levels ≥30 ng/ml) was not observed in any of the patients who were receiving placebo, while repletion was observed in 16 of 33 patients receiving vitamin D3 . The percentage of patients with an IFN signature response did not differ among the treatment groups. Moreover, there was no difference in the percentage of patients with an IFN signature response between those who remained vitamin D deficient and those who demonstrated repletion of vitamin D. Modular microarray analysis of a subset of patients (n = 40) did not reveal changes from baseline in any modules (including the IFN-inducible module) in any of the treatment groups, and no differences in expression were found between patients who demonstrated vitamin D repletion and patients who were persistently vitamin D deficient. Vitamin D3 was well tolerated, and there were no safety concerns., Conclusion: Vitamin D3 supplementation up to 4,000 IU daily was safe and well-tolerated but failed to diminish the IFN signature in vitamin D-deficient SLE patients. Higher 25(OH)D levels sustained for a longer duration may be required to affect immunologic outcomes., (© 2015, American College of Rheumatology.)

Broadly HIV-1-neutralizing antibodies (BnAbs) display one or more unusual traits, including a long heavy chain complementarity-determining region 3 (HCDR3), polyreactivity, and high levels of somatic mutations. These shared characteristics suggest that BnAb development might be limited by immune tolerance controls. It has been postulated that HIV-1-infected individuals with autoimmune disease and defective immune tolerance mechanisms may produce BnAbs more readily than those without autoimmune diseases. In this study, we identified an HIV-1-infected individual with SLE who exhibited controlled viral load (<5,000 copies/ml) in the absence of controlling HLA phenotypes and developed plasma HIV-1 neutralization breadth. We collected memory B cells from this individual and isolated a BnAb, CH98, that targets the CD4 binding site (CD4bs) of HIV-1 envelope glycoprotein 120 (gp120). CH98 bound to human antigens including dsDNA, which is specifically associated with SLE. Anti-dsDNA reactivity was also present in the patient's plasma. CH98 had a mutation frequency of 25% and 15% nt somatic mutations in the heavy and light chain variable domains, respectively, a long HCDR3, and a deletion in the light chain CDR1. The occurrence of anti-dsDNA reactivity by a HIV-1 CD4bs BnAb in an individual with SLE raises the possibility that some BnAbs and SLE-associated autoantibodies arise from similar pools of B cells.

Background: Depressive symptoms affect anywhere from 11% to 71% of patients with systemic lupus erythematosus (SLE), which may be related to SLE disease activity, other clinical variables, or sociodemographic factors., Objective: We aimed to measure the rate of depressive symptoms in our cohort of patients with SLE and to identify modifiable factors associated with depressive symptoms., Methods: Patients in our university-based SLE registry completed the Beck Depression Inventory-II (BDI-II), pain scores, and demographic information. Disease activity was measured using the physician's global assessment (PGA) and Selena-SLE disease activity index (Selena-systemic lupus erythematosus disease activity index (SLEDAI)). Patients were identified as having moderate or severe depressive symptoms (BDI-II ≥ 18) or not (BDI-II < 18). Nonparametric tests and χ(2) tests were used as appropriate to compare variables between groups., Results: Fifty-three of 127 people (41.7%) were identified as having moderate or severe depressive symptoms, which were associated with higher pain levels and lower self-reported of current health status. Patients with moderate or severe depressive symptoms were more likely (49%) than those with no or mild depressive symptoms (18%) to have lupus arthritis (P < 0.01). Of the 53 patients with moderate or severe depressive symptoms, only 26 (49.0%) were prescribed antidepressants, and only 8/53 patients (15.0%) were prescribed the maximum dose of antidepressant., Conclusions: This study identified moderate or severe depressive symptoms in 41.7% of our cohort of patients with SLE. The most significant variable associated with these symptoms was pain; improved treatment of pain, and in particular from lupus arthritis, may result in alleviation of depressive symptoms in patients with SLE., (Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: While increased disease activity is the best predictor of preterm birth in women with systemic lupus erythematosus (SLE), even women with low disease activity are at increased risk of this complication. Biomarkers that would identify at-risk pregnancies could allow interventions to prevent preterm birth., Method: Measures of SLE activity, inflammation, placental health and renal function between 20 and 28 weeks gestation (mid-gestation) were correlated to preterm birth and gestational age at delivery in a prospective cohort of pregnant women with SLE., Result: Of the 40 pregnancies in 39 women, all with mild-moderate SLE disease, 9 (23.7%) of the 38 live births were delivered preterm. Low C4 was the only marker of SLE activity associated with younger gestational age at delivery. Elevated ferritin and lower oestradiol correlated with younger gestational age at delivery. Renal function remained normal during all pregnancies at mid-gestation and did not correlate with preterm birth. Higher serum uric acid, however, correlated with younger gestational age at delivery., Conclusions: In women with SLE with mild-moderate disease activity, ferritin, oestradiol and uric acid levels at mid-gestation may predict preterm birth. These markers may prove to be clinically useful in identifying pregnancies at particularly high risk for adverse outcomes.

Objective: American Council on Graduate Medical Education program requirements mandate that rheumatology training programs have written goals, objectives, and performance evaluations for each learning activity. Since learning activities are similar across rheumatology programs, we aimed to create competency-based goals and objectives (CBGO) and evaluations that would be generalizable nationally., Methods: Through an established collaboration of the 4 training programs' directors in North Carolina and South Carolina, we collaboratively composed CBGO and evaluations for each learning activity for rheumatology training programs. CBGO and linked evaluations were written using appropriate verbs based on Bloom's taxonomy. Draft documents were peer reviewed by faculty at the 4 institutions and by members of the American College of Rheumatology (ACR) Clinician Scholar Educator Group., Results: We completed templates of CBGO for core and elective rotations and conferences. Templates detail progressive fellow performance improvement appropriate to educational level. Specific CBGO are mirrored in learning activity evaluations. Templates are easily modified to fit individual program attributes, have been successfully implemented by our 4 programs, and have proven their value in 4 residency review committee reviews., Conclusion: We propose adoption of these template CBGO by the ACR, with access available to all rheumatology training programs. Evaluation forms that exactly reflect stated objectives ensure that trainees are assessed using standardized measures and that trainees are aware of the learning expectations. The objectives mirrored in the evaluations closely align with the proposed milestones for internal medicine training, and will therefore be a useful starting point for creating these milestones in rheumatology., (Copyright © 2013 by the American College of Rheumatology.)

Systemic lupus erythematosus is a prototypic autoimmune disease characterized by antibodies to DNA and other nuclear molecules. While these antibodies can form immune complexes, the mechanisms generating the bound nuclear antigens are not known. These studies investigated whether microparticles can form complexes with anti-DNA and other anti-nucleosomal antibodies. Microparticles are small membrane-bound vesicles released from dead and dying cells; these particles contain a variety of cellular components, including DNA. To assess antigenicity, microparticles generated in vitro from apoptotic cell lines were tested using murine monoclonal anti-DNA and anti-nucleosomal antibodies as well as plasma from lupus patients. Antibody binding was assessed by flow cytometry. As these studies showed, some but not all of the monoclonal antibodies bound to microparticles prepared from apoptotic HL-60, THP-1 and Jurkat cells. For HL-60 cells, both staurosporine and UV radiation led to the production of antigenically active particles. For the anti-DNA antibody with high particle binding, prior treatment of DNase reduced activity. With plasma from patients with SLE, antibody binding to microparticles was present although a clear relationship with anti-DNA antibody levels was not observed. To determine whether lupus plasma contains immune complexes with particle properties, particle preparations were tested for bound IgG by flow cytometry. These studies indicated that lupus plasma contains particles with IgG binding, with numbers correlated with anti-DNA levels. Together, these findings indicate that microparticles display DNA and nucleosomal molecules in an antigenic form and could represent a source of immune complexes in SLE., (Copyright © 2011 Elsevier Ltd. All rights reserved.)