Blood-based biomarkers of neuronal and glial injury in active major neuropsychiatric systemic lupus erythematosus.

BACKGROUND: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE. METHODS: This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6 months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected. RESULTS: Thirteen patients with active major NPSLE, 13 age/sex/kidney function matched SLE controls without active major NPSLE, and 13 age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6 years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3 pg/ml (p = .42) and 1.2 pg/ml higher (p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2 pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy. CONCLUSIONS: Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting.

Improved executive function in patients with systemic lupus erythematosus following interactive digital training.

OBJECTIVE: This study aimed to evaluate the sensitivity of a digital platform to assess attentional and executive function in systemic lupus erythematosus (SLE) patients, and to evaluate the impact of an at-home interactive digital treatment to improve cognitive dysfunction in this clinical population. BACKGROUND: Deficits in attention and executive function are common in patients with SLE. Despite these cognitive difficulties, there are limited brief assessment techniques and few treatment options to improve cognitive abilities in patients with SLE. Interactive digital treatment approaches (use of video game-based software) have been successful in identifying and improving cognition in other clinical populations. METHODS: Sixty SLE patients completed baseline neuropsychological tests (of attention, psychomotor speed, and executive function), a tablet-based digital platform (EVOTM Monitor), and biobehavioral measures. The patients were randomized into treatment SLE (n = 30) or no contact control SLE (n = 30) groups, and returned 4 weeks later for follow-up cognitive, EVO Monitor, and biobehavioral testing. The SLE treatment group was trained on a tablet-based digital treatment (AKL-T01) and was instructed to complete 5 sessions at least 5 days per week for 4-weeks for a total of approximately 25 min of gameplay per day. RESULTS: Systemic lupus erythematosus patients demonstrated impairment in visuomotor and processing speed, visual attention, and cognitive flexibility/sequencing skills at baseline. The video game-like treatment group (AKL-T01) had significant improvement in visuomotor speed (Trail Making A) and cognitive flexibility/sequencing (Trail Making B) compared to the control group at 4-week follow-up. The treatment group also demonstrated significant improvement in EVO Monitor multitasking at follow-up (with no change in controls). At baseline, a multitasking metric from EVO Monitor was associated with performance on tasks of cognitive flexibility (Trail Making B) and psychomotor speed (WAIS-IV Coding). CONCLUSIONS: These findings provide evidence that SLE patients who participated in a 4-week interactive digital video game-like activity had significant improvement in motor speed and executive functions, and would benefit from participation in digital interventions designed to target frontoparietal networks of the brain. Preliminary findings also suggest specific metrics from EVO Monitor may also be useful to detect cognitive impairment and cognitive changes in patients with SLE.

Consensus-Derived Recommended Skills for Transition to Residency Courses.

PURPOSE: Transition to residency (TTR) courses facilitate the medical student-residency transition and are an integral part of senior medical student training. The authors established a common set of skills for TTR courses, and an expected level of entrustment students should demonstrate in each skill on TTR course completion. METHOD: A modified Delphi approach was used with 3 survey iterations between 2020 and 2022 to establish skills to be included in a TTR course. Nine TTR experts suggested general candidate skills and conducted a literature search to ensure no vital skills were missed. A stakeholder panel was solicited from email lists of TTR educators, residency program directors, and residents at the panelists' institutions. Consensus was defined as more than 75% of participants selecting a positive inclusion response. An entrustment questionnaire asked panelists to assign a level of expected entrustment to each skill, with 1 indicating observation only and 6 indicating perform independently. RESULTS: The stakeholder panel initially consisted of 118 respondents with representation across educational contexts and clinical specialties. Response rates were 54% in iteration 2, 42% in iteration 3, and 33% on the entrustment questionnaire. After 3 iterations, 54 skills met consensus and were consolidated into 37 final skills categorized into 18 clinical skills (e.g., assessment and management of inpatient concerns), 14 communication skills (e.g., delivering serious news or having difficult conversations), 4 personal and professional skills (e.g., prioritization of clinical tasks), and 1 procedural skill (mask ventilation). Median entrustment levels were reported for all skills, with 19 skills having a level of expected entrustment of 4 (perform independently and have all findings double-checked). CONCLUSIONS: These consensus skills can serve as the foundation of a standardized national TTR curriculum framework. Entrustment guidance may help educational leaders optimize training and allocation of resources for TTR curriculum development and implementation.

Leveraging the Consolidated Framework for Implementation Research (CFIR) to Develop the American College of Rheumatology's Toolkit for Implementation of Rheumatoid Arthritis Outcome Measures in Clinical Practice: A Qualitative Study.

OBJECTIVE: Despite the recognized benefits of collecting rheumatoid arthritis (RA) outcomes measures, their use in routine care is inconsistent. Using the Consolidated Framework for Implementation Research (CFIR), we conducted semi-structured interviews with United States rheumatologists and practice personnel to assess workflows, opportunities, and challenges in collecting RA outcome measures. Using insights from interviews, we developed the RA Measures Toolkit to enhance their utilization in clinical practice. METHODS: We invited 138 RISE registry practices and 5 academic medical centers with ≥ 30 patients eligible for RA outcome measures to participate in the study. Practices were classified based on their performance in quality payment programs. Recorded interviews were transcribed verbatim and analyzed thematically using deductive and inductive techniques. The findings were used to create the RA Measures Toolkit. RESULTS: We conducted 20 interviews with 38 participants across 20 practices. Key themes within the CFIR domains highlighted the challenges and best practices in RA outcome measure collection and included: 1) Process: the variability in practices' use of RA outcome measures and the importance of streamlined workflows, 2) Intervention: challenges of integrating PROs into electronic health records (EHRs), and 3) Individual characteristics: importance of clinic culture around quality improvement. Using this data, we developed the RA Toolkit, a multimedia online resource, featuring guidelines, best practices, and educational resources to improve the efficiency of current workflows and to enhance patient care. CONCLUSION: This study identifies critical gaps in the collection of RA outcome measures in U.S. rheumatology practices and provides actionable recommendations and resources to address challenges via the RA Toolkit.

Development of American College of Rheumatology Quality Measures for Systemic Lupus Erythematosus: A Modified Delphi Process With Rheumatology Informatics System for Effectiveness (RISE) Registry Data Review.

OBJECTIVE: We aimed to develop readily measurable digital quality measure statements for clinical care in systemic lupus erythematosus (SLE) using a multistep process guided by consensus methods. METHODS: Using a modified Delphi process, an American College of Rheumatology (ACR) workgroup of SLE experts reviewed all North American and European guidelines from 2000 to 2020 on treatment, monitoring, and phenotyping of patients with lupus. Workgroup members extracted quality constructs from guidelines, rated these by importance and feasibility, and generated evidence-based quality measure statements. The ACR Rheumatology Informatics System for Effectiveness (RISE) Registry was queried for measurement data availability. In 3 consecutive Delphi sessions, a multidisciplinary Delphi panel voted on the importance and feasibility of each statement. Proposed measures with consensus on feasibility and importance were ranked to identify the top 3 measures. RESULTS: Review of guidelines and distillation of 57 quality constructs resulted in 15 quality measure statements. Among these, 5 met high consensus for importance and feasibility, including 2 on treatment and 3 on laboratory monitoring measures. The 3 highest-ranked statements were recommended for further measure specification as SLE digital quality measures: 1) hydroxychloroquine use, 2) limiting glucocorticoid use >7.5 mg/day to <6 months, and 3) end-organ monitoring of kidney function and urine protein excretion at least every 6 months. CONCLUSION: The Delphi process selected 3 quality measures for SLE care on hydroxychloroquine, glucocorticoid reduction, and kidney monitoring. Next, measures will undergo specification and validity testing in RISE and US rheumatology practices as the foundation for national implementation and use in quality improvement programs.

Quality of care in systemic lupus erythematosus: application of quality measures to understand gaps in care.

BACKGROUND: Systemic lupus erythematosus (SLE) affects 1 in 2500 Americans and is associated with significant morbidity and mortality. The recent development of SLE quality measures provides an opportunity to understand gaps in clinical care and to identify modifiable factors associated with variations in quality. OBJECTIVE: To evaluate performance on SLE quality measures as well as differences in quality of care by demographic, socioeconomic, disease, and health system characteristics. DESIGN AND PATIENTS: Cross-sectional analysis of data derived from the Lupus Outcomes Study, a prospective, longitudinal study of 814 individuals. Principal data collection was through annual structured telephone surveys between 2009-2010. Data on 13 SLE quality measures was collected. We used regression models to estimate demographic, socioeconomic, disease, and health system characteristics associated with performance on individual and overall quality measures. OUTCOME MEASURES: Performance on each quality measure and overall performance on all measures for which participants were eligible (pass rate). RESULTS: Participants were eligible for a mean of five measures (range 2-12). Performance varied from 29 % (assessment of cardiovascular risk factors) to 90 % (sun avoidance counseling). The overall pass rate was 65 % (95 % CI 64 %, 65 %). In unadjusted analyses, younger age, minority race/ethnicity, poverty, shorter disease duration, fewer physician visits, and lack of health insurance, were associated with lower pass rates. Receiving care in public sector managed care organizations was associated with higher pass rates. After adjustment, younger age, having fewer physician visits and lacking health insurance remained significantly associated with lower performance; receiving care in public sector managed care organizations remained associated with higher performance. CONCLUSIONS: We identified a number of gaps in clinical care for SLE. Factors associated with the health care system, including presence and type of health insurance, were the primary determinants of performance on quality measures in SLE.

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1ß, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.

The Development of the Rheumatology Informatics System for Effectiveness Learning Collaborative for Improving Patient-Reported Outcome Collection and Patient-Centered Communication in Adult Rheumatology.

OBJECTIVE: Patient-reported outcomes (PROs) are an integral part of treat-to-target approaches in managing rheumatoid arthritis (RA). In clinical practice, however, routine collection, documentation, and discussion of PROs with patients are highly variable. The RISE LC (Rheumatology Informatics System for Effectiveness Learning Collaborative) was established to develop and share best practices in PRO collection and use across adult rheumatology practices in the United States METHODS: The goals of the RISE LC were developed through site surveys and in-person meetings. Participants completed a baseline survey on PRO collection and use in their practices. RISE LC learning sessions focused on improving communication around PROs with patients and enhancing shared decision-making in treatment plans. During the coronavirus disease 2019 (COVID-19) pandemic, the RISE LC pivoted to adapt PRO tools for telehealth. RESULTS: At baseline, all responding sites (n = 15) had established workflows for collecting PROs. Most sites used paper forms alone. PRO documentation in electronic health records was variable, with only half of the sites using structured data fields. To standardize and improve the use of PROs, participants iteratively developed a Clinical Disease Activity Index-based RA Disease Activity Communication Tool to solicit treatment goals and improve shared decision-making across sites. The COVID-19 pandemic necessitated developing a tool to gauge PROs via telehealth. CONCLUSION: The RISE LC is a continuous, structured method for implementing strategies to improve PRO collection and use in rheumatological care, initially adapting from the Learning Collaborative model and extending to include features of a learning network. Future directions include measuring the impact of standardized PRO collection and discussion on shared decision-making and RA outcomes.

Systematic Review and Appraisal of the Cross-Cultural Validity of Functional Status Assessment Measures in Rheumatoid Arthritis.

OBJECTIVE: We conducted a systematic review and appraisal of the cross-cultural adaptation and cross-cultural validity of the Health Assessment Questionnaire (HAQ) and its derivatives, and of the more recent Patient-Reported Outcomes Measurement Information System (PROMIS) functional status assessment measures (FSAMs) in rheumatoid arthritis. METHODS: Four electronic medical databases were searched from inception until April 4, 2018 according to the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) group search strategy. Included studies were evaluated using the COSMIN tool for cross-cultural validity and were scored as excellent, good, fair, or poor. RESULTS: Of 58 articles identified by our search strategy and 3 by manual search, 39 were included: 29 described the translation, cultural adaptation, or cross-cultural validity of the HAQ disability index, 8 other HAQ derivatives, and 2 PROMIS measures, representing 22 languages. Of the 39 articles reviewed, 3 examined the cross-cultural validity of translated versions. These studies were rated as follows: 2 as excellent, 3 good, 13 fair, and 21 poor. Two studies examining cross-cultural validity noted differential item functioning (DIF) between Dutch and US populations for the HAQ-II and PROMIS measures, and a third study found DIF between Turkish and UK populations on the HAQ, indicating cultural differences in questionnaire response. CONCLUSION: This review highlights a paucity of data on the cross-cultural validity of FSAMs and the mostly poor- or fair-quality methods by which they were translated and adapted, which needs to be considered when using these measures for multinational clinical trials and for day-to-day use in clinical practice.

2019 American College of Rheumatology Recommended Patient-Reported Functional Status Assessment Measures in Rheumatoid Arthritis.

OBJECTIVE: To develop American College of Rheumatology (ACR) recommendations for patient-reported Functional Status Assessment Measures (FSAMs) for use in routine clinical practice in patients with rheumatoid arthritis (RA). METHODS: We convened a workgroup to conduct a systematic review of published literature through March 16, 2017 and abstract FSAM properties. Based upon initial search results and clinical input, we focused on the following FSAMs appropriate for routine clinical use: the Health Assessment Questionnaire (HAQ) and derived measures and the Patient-Reported Outcomes Measurement Information System (PROMIS) tool. We used the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) 4-point scoring method to evaluate each FSAM, allowing for overall level of evidence assessment. We identified FSAMs fulfilling a predefined minimum standard and, through a modified Delphi process, selected preferred FSAMs for regular use in most clinic settings. RESULTS: The search identified 11,835 articles, of which 56 were included in the review. Descriptions of the measures, properties, study quality, level of evidence, and feasibility were abstracted and scored. Following a modified Delphi process, 7 measures fulfilled the minimum standard for regular use in most clinic settings, and 3 measures were recommended: the PROMIS physical function 10-item short form (PROMIS PF10a), the HAQ-II, and the Multidimensional HAQ. CONCLUSION: This work establishes ACR recommendations for preferred RA FSAMs for regular use in most clinic settings. These results will inform clinical practice and can support future ACR quality measure development as well as highlight ongoing research needs.

Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System.

OBJECTIVE: In 2013, the American College of Rheumatology (ACR) participated in the Choosing Wisely campaign and devised a recommendation to avoid testing antinuclear antibody (ANA) subserologies without a positive ANA and clinical suspicion of disease. The goals of our study were to describe ANA and subserology ordering practices and predictors of ordering concurrent ANA and subserologies in a safety-net hospital. METHODS: We identified ANA and subserologies (dsDNA, Sm, RNP, SSA, SSB, Scl-70 and centromere) completed at Denver Health between 1/1/2005 and 12/31/2011. Variables included demographics, primary insurance, service, and setting from which the test was ordered. We performed multivariable logistic regression to determine predictors of concurrent ordering of ANA and subserologies. RESULTS: During seven years, 3221 ANA were performed in 2771 individuals and 211 (6.6%) were performed concurrently with at least one subserology. The most common concurrent subserologies were dsDNA (21.8%), SSA (20.8%), and SSB (19.7%). In the multivariable logistic analysis, significant predictors of concurrent ANA and subserologies were the labs being ordered from subspecialty care (OR 8.12, 95% CI 5.27-12.50, p-value <0.0001) or from urgent/inpatient care (OR 3.86, 95% CI 1.78-8.38, p-value 0.001). A significant predictor of decreased odds was male gender (OR 0.32, 95% CI 0.21-0.49, p-value <0.0001). Five individuals (2.2% of the negative ANA with subserologies ordered) had a negative ANA but positive subserologies. CONCLUSION: Of 3221 ANA, 6.6% were performed concurrently with subserologies, and subspecialists were more likely to order concurrent tests. A negative ANA predicted negative subserologies with rare exceptions, which validates the ACR's recommendations.

Choosing wisely: the American College of Rheumatology's Top 5 list of things physicians and patients should question.

OBJECTIVE: We sought to develop a list of 5 tests, treatments, or services commonly used in rheumatology practice whose necessity or value should be questioned and discussed by physicians and patients. METHODS: We used a multistage process combining consensus methodology and literature reviews to arrive at the American College of Rheumatology's (ACR) Top 5 list. Rheumatologists from diverse practice settings generated items using the Delphi method. Items with high content agreement and perceived high prevalence advanced to a survey of ACR members, who comprise >90% of the US rheumatology workforce. To increase the response rate, a nested random sample of 390 rheumatologists received more intensive survey followup. The samples were combined and weighting procedures were applied to ensure generalizability. Items with high ratings underwent literature review. Final items were then selected and formulated by the task force. RESULTS: One hundred five unique items were proposed and narrowed down to 22 items during the Delphi rounds. A total of 1,052 rheumatologists (17% of those contacted) participated in the member-wide survey, whereas 33% of those in the nested random sample participated; respondent characteristics were similar in both samples. Based on survey results and available scientific evidence, 5 items (relating to antinuclear antibodies, Lyme disease, magnetic resonance imaging, bone absorptiometry, and biologic therapy for rheumatoid arthritis) were selected for inclusion. CONCLUSION: The ACR Top 5 list is intended to promote discussions between physicians and patients about health care practices in rheumatology whose use should be questioned and to assist rheumatologists in providing high-value care.