Trajectories of depressive symptoms in systemic lupus erythematosus over time.

OBJECTIVES: The objectives of this study were to determine the trajectories of depressive symptoms in patients with SLE and to identify baseline characteristics that are associated with a patient's trajectory of depression. METHODS: Data from the Lupus Outcomes Study at the University of California, San Francisco were analysed. Depressive symptomatology was assessed in years two through seven using the Center for Epidemiologic Studies Depression Scale (CES-D), with higher scores representing more severe depressive symptoms. Group-based trajectory modelling was used to determine latent classes of CES-D scores over time. Ordinal logistic regression analyses were performed to identify baseline characteristics associated with worse classes of depressive symptoms. RESULTS: CES-D scores for 763 individuals with SLE over 6 years were mapped into four distinct classes. Class 1 (36%) and class 2 (32%) comprised the largest proportion of the cohort and were defined by the lowest and low CES-D scores (no depression), respectively. Class 3 (22%) and class 4 (10%) had high and the highest scores (depression), respectively. Greater age [odds ratio (OR): 0.97, 95% CI: 0.96, 0.99] and higher education level (OR: 0.79, 95% CI: 0.70, 0.89) at baseline were associated with lower odds of membership in worse classes of depressive symptoms. Conversely, lower income (OR: 1.73, 95% CI: 1.03, 2.92), worse SF-36 physical functioning scores (OR: 1.12, 95% CI: 1.12, 1.13) and worse SF-36 bodily pain scores (OR: 1.58, 95% CI: 1.55, 1.61) were positively associated with membership in worse classes of depressive symptoms. CONCLUSION: Four classes of depressive symptoms were identified in patients with SLE. Understanding the trajectories of depressive symptoms and the associated risk factors can aid in the management of these symptoms in individuals living with SLE.

The association of trauma with self-reported flares and disease activity in systemic lupus erythematosus (SLE).

OBJECTIVES: Trauma has been linked to incident SLE, but its relationship with SLE disease activity is unknown. This analysis examines associations between trauma exposures and patient-reported SLE disease activity and flares. METHODS: Data were from the California Lupus Epidemiology Study (CLUES). Flares were self-reported as any flare and, of those, flares accompanied by medical care (hospitalization or physician contact). The Systemic Lupus Activity Questionnaire (SLAQ) assessed disease activity. The Brief Trauma Questionnaire (BTQ) assessed all historical trauma exposures. The Adverse Childhood Experiences (ACEs) questionnaire was available for a subset. Multivariable regression analyses (n = 252) examined whether trauma exposure was associated with flares or SLAQ controlling for age, sex, poverty, race/ethnicity, comorbidities, perceived stress, disease duration and self-reported disease damage. RESULTS: Excluding exposure to serious illness, 63.4% reported ≥1 trauma exposure. Any traumatic event, excluding illness, doubled the odds of a flare [OR 2.27 (95% CI 1.24, 4.17)] and was associated with significantly higher SLAQ scores [ß 2.31 (0.86, 3.76)]. Adjusted odds of any flare and flare with medical care were significantly elevated for those with both BTQ and ACE exposures [5.91 (2.21, 15.82) and 4.69 (1.56, 14.07), respectively]. SLAQ scores were also higher for those with both exposures [ß 5.22 (3.00, 7.44)]. CONCLUSION: In this cohort, those with a history of trauma reported more flares and greater disease activity. Identifying mechanisms of associations between trauma and disease activity and flares, as well as interventions to mitigate the effects of trauma exposures is critical, given the high rates of trauma exposures.

Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment.

OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.

Association of mycophenolate and azathioprine use with cognitive function in systemic lupus.

OBJECTIVES: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. METHODS: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. RESULTS: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. CONCLUSION: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Medication Cost Concerns and Disparities in Patient-Reported Outcomes Among a Multiethnic Cohort of Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Concerns about the affordability of medications are common in systemic lupus erythematosus (SLE), but the relationship between medication cost concerns and health outcomes is poorly understood. We assessed the association of self-reported medication cost concerns and patient-reported outcomes (PROs) in a multiethnic SLE cohort. METHODS: The California Lupus Epidemiology Study is a cohort of individuals with physician-confirmed SLE. Medication cost concerns were defined as having difficulties affording SLE medications, skipping doses, delaying refills, requesting lower-cost alternatives, purchasing medications outside the United States, or applying for patient assistance programs. Linear regression and mixed effects models assessed the cross-sectional and longitudinal association of medication cost concerns and PROs, respectively, adjusting for age, sex, race and ethnicity, income, principal insurance, immunomodulatory medications, and organ damage. RESULTS: Of 334 participants, medication cost concerns were reported by 91 (27%). Medication cost concerns were associated with worse Systemic Lupus Activity Questionnaire (SLAQ; beta coefficient [ß] 5.9, 95% CI 4.3-7.6; P < 0.001), 8-item Patient Health Questionnaire depression scale (PHQ-8; ß 2.7, 95% CI 1.4-4.0; P < 0.001), and Patient-Reported Outcomes Measurement Information System (PROMIS; ß for physical function -4.6, 95% CI -6.7 to -2.4; P < 0.001) scores after adjusting for covariates. Medication cost concerns were not associated with significant changes in PROs over 2-year follow-up. CONCLUSION: More than a quarter of participants reported at least 1 medication cost concern, which was associated with worse PROs. Our results reveal a potentially modifiable risk factor for poor outcomes rooted in the unaffordability of SLE care.

Does higher quality of care in systemic lupus erythematosus translate to better patient outcomes?

PURPOSE: To assess if high quality of care (QOC) in SLE results in improved outcomes of quality of life (QOL) and non-routine health care utilization (HCU). METHODS: One hundred and forty consecutive SLE patients were recruited from the Rheumatology clinic at an academic center. Data on QOC and QOL were collected along with demographics, socio-economic, and disease characteristics at baseline. LupusPRO assessing health-related (HR) QOL and non (N)HRQOL was utilized. Follow up QOL and HCU were collected prospectively at 6 months. High QOC was defined as those meeting ≥80% of the eligible quality indicators. Univariate and multivariate regression analyses were performed with QOC and high QOC as independent variables and HRQOL and NHRQOL as dependent variables at baseline and follow up. Multivariable models were adjusted for demographics and disease characteristics. Secondary outcomes included non-routine HCU and disease activity at follow up. RESULTS: Baseline and follow up data on 140 and 94 patients, respectively, were analyzed. Mean (SD) performance rate (QOC) was 78.6 (13.4) with 52% patients in the high QOC group. QOC was associated with better NHRQOL at baseline and follow up but not with HRQOL. Of all the NHRQOL domains, QOC was positively associated with treatment satisfaction. QOC or high QOC were not associated with non-routine HCU and were instead associated with higher disease activity at follow up. CONCLUSION: Higher QOC predicted better NHRQOL by directly impacting treatment satisfaction in SLE patients in this cohort. Higher QOC, however, was not associated with HRQOL, HCU, or improvement in disease activity at follow up.

Are Patient-Reported Outcome Measures for Distal Radius Fractures Validated for Spanish and Culture? A Systematic Review.

PURPOSE: Patient-reported outcome measures (PROMs) are used commonly to assess function to direct treatment and evaluate outcomes for patients with distal radius fractures. Most PROMs have been developed and validated in English with minimal report of the demographics of patients studied. The validity of applying these PROMs among Spanish-speaking patients is unknown. The purpose of this study was to evaluate the quality and psychometric properties of Spanish-language adaptations of PROMs for distal radius fractures. METHODS: We conducted a systematic review to identify published studies of adaptations of Spanish-language PROMs evaluating patients with distal radius fractures. We evaluated the methodologic quality of the adaptation and validation using Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures, Quality Criteria for Psychometric Properties of Health Status Questionnaire, and the Consensus-based Standards for the Selection of Health Measurement Instruments Checklist for Cross-Cultural Validity. The level of evidence was evaluated based upon prior methodology. RESULTS: Five instruments reported in eight studies were included: the Patient-Rated Wrist Evaluation (PRWE), Disability of Arm Shoulder and Hand, Upper Limb Functional Index, Lawton Instrumental Activities of Daily Living Scale, and Short Musculoskeletal Function Assessment. The PRWE was the most frequently included PROM. No study followed all six processes for adaptation or assessed all measurement properties. No study demonstrated the completion of more than eight of the 14 aspects of cross-cultural validity. The PRWE had moderate evidence to support half of the domains of measurement properties evaluating the level of evidence. CONCLUSIONS: None of the five instruments identified received a good rating on all three checklists. Only the PWRE demonstrated moderate evidence on half of the measurement domains. CLINICAL RELEVANCE: Given the lack of strong evidence to support the quality of these instruments, we recommend adaptation and testing of PROMs for this population before use. Currently, PROMs in Spanish-speaking patients should be used with caution so as not to perpetuate health care disparities.

Depressive symptoms in lung transplant recipients: trajectory and association with mortality and allograft dysfunction.

OBJECTIVE: Most studies observing an association between depressive symptoms following lung transplantation and mortality are limited to depressive symptom measurement at a single time point, unrelated to allograft function. We aimed to test the association of depressive symptoms over multiple assessments with allograft dysfunction and with mortality. METHODS: We assessed depressive symptoms before and serially up to 3 years after lung transplantation in lung transplant recipients. We quantified depressive symptoms with the Geriatric Depression Scale (GDS; range 0-15; minimally important difference (MID): 2). We quantified changes in GDS using linear mixed effects models and tested the association with mortality using Cox proportional hazards models with GDS as a time-dependent predictor. To determine if worsening in GDS preceded declines in lung function, we tested the association of GDS as a time-dependent predictor with the lagged outcome of FEV1 at the following study visit. RESULTS: Among 266 participants, depressive symptoms improved early after transplantation. Worsening in post-transplant GDS by the MID was associated with mortality (HR 1.25, 95% CI 1.05 to 1.50), and in lagged outcome analyses with decreased per cent predicted FEV1 (Δ, -1.62%, 95% CI -2.49 to -0.76). Visual analyses of temporal changes in GDS demonstrated that worsening depressive symptoms could precede chronic lung allograft dysfunction. CONCLUSIONS: Depressive symptoms generally improve after lung transplantation. When they worsen, however, there is an association with declines in lung function and mortality. Depression is one of the few, potentially modifiable, risk factors for chronic lung allograft dysfunction and death.

Sarcopenic obesity in rheumatoid arthritis: prevalence and impact on physical functioning.

OBJECTIVE: We determined the prevalence of sarcopenic obesity in patients with RA using multiple methods and assessed associations with physical functioning. METHODS: This study evaluated data from three RA cohorts. Whole-body dual-energy absorptiometry (DXA) measures of appendicular lean mass index (ALMI, kg/m2) and fat mass index (FMI) were converted to age, sex and race-specific Z-Scores and categorized using a recently validated method and compared it to a widely-used existing method. The prevalence of body composition abnormalities in RA was compared with two reference populations. In the RA cohorts, associations between body composition and change in the HAQ and the Short Physical Performance Battery (SPPB) in follow-up were assessed using linear and logistic regression, adjusting for age, sex, race and study. RESULTS: The prevalence of low lean mass and sarcopenic obesity was higher in patients with RA (14.2; 12.6%, respectively) compared with the reference population cohorts (7-10%; 4-4.5%, respectively, all P <0.05). There was only moderate agreement among methods of sarcopenic obesity categorization (Kappa 0.45). The recently validated method categorized fewer subjects as obese, and many of these were categorized as low lean mass only. Low lean mass, obesity and sarcopenic obesity were each associated with higher HAQ and lower SPPB at baseline and numerically greater worsening. CONCLUSION: RA patients had higher rates of low lean mass and sarcopenic obesity than the general population. The recently validated methods characterized body composition changes differently from traditional methods and were more strongly associated with physical function.

Validation of the automated neuropsychological assessment metrics for assessing cognitive impairment in systemic lupus erythematosus.

OBJECTIVE: We previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis. METHODS: 300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs. RESULTS: Two models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results. CONCLUSION: We provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

Effect of Immunosuppression on the Immunogenicity of mRNA Vaccines to SARS-CoV-2 : A Prospective Cohort Study.

BACKGROUND: Patients with chronic inflammatory disease (CID) treated with immunosuppressive medications have increased risk for severe COVID-19. Although mRNA-based SARS-CoV-2 vaccination provides protection in immunocompetent persons, immunogenicity in immunosuppressed patients with CID is unclear. OBJECTIVE: To determine the immunogenicity of mRNA-based SARS-CoV-2 vaccines in patients with CID. DESIGN: Prospective observational cohort study. SETTING: Two U.S. CID referral centers. PARTICIPANTS: Volunteer sample of adults with confirmed CID eligible for early COVID-19 vaccination, including hospital employees of any age and patients older than 65 years. Immunocompetent participants were recruited separately from hospital employees. All participants received 2 doses of mRNA vaccine against SARS-CoV-2 between 10 December 2020 and 20 March 2021. Participants were assessed within 2 weeks before vaccination and 20 days after final vaccination. MEASUREMENTS: Anti-SARS-CoV-2 spike (S) IgG+ binding in all participants, and neutralizing antibody titers and circulating S-specific plasmablasts in a subset to assess humoral response after vaccination. RESULTS: Most of the 133 participants with CID (88.7%) and all 53 immunocompetent participants developed antibodies in response to mRNA-based SARS-CoV-2 vaccination, although some with CID developed numerically lower titers of anti-S IgG. Anti-S IgG antibody titers after vaccination were lower in participants with CID receiving glucocorticoids (n = 17) than in those not receiving them; the geometric mean of anti-S IgG antibodies was 357 (95% CI, 96 to 1324) for participants receiving prednisone versus 2190 (CI, 1598 to 3002) for those not receiving it. Anti-S IgG antibody titers were also lower in those receiving B-cell depletion therapy (BCDT) (n = 10). Measures of immunogenicity differed numerically between those who were and those who were not receiving antimetabolites (n = 48), tumor necrosis factor inhibitors (n = 39), and Janus kinase inhibitors (n = 11); however, 95% CIs were wide and overlapped. Neutralization titers seemed generally consistent with anti-S IgG results. Results were not adjusted for differences in baseline clinical factors, including other immunosuppressant therapies. LIMITATIONS: Small sample that lacked demographic diversity, and residual confounding. CONCLUSION: Compared with nonusers, patients with CID treated with glucocorticoids and BCDT seem to have lower SARS-CoV-2 vaccine-induced antibody responses. These preliminary findings require confirmation in a larger study. PRIMARY FUNDING SOURCE: The Leona M. and Harry B. Helmsley Charitable Trust, Marcus Program in Precision Medicine Innovation, National Center for Advancing Translational Sciences, and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Primary graft dysfunction attenuates improvements in health-related quality of life after lung transplantation, but not disability or depression.

Disability, depressive symptoms, and impaired health-related quality of life (HRQL) are common among patients with life-threatening respiratory compromise. We sought to determine if primary graft dysfunction (PGD), a syndrome of acute lung injury, attenuates improvements in patient-reported outcomes after transplantation. In a single-center prospective cohort, we assessed disability, depressive symptoms, and HRQL before and at 3- to 6-month intervals after lung transplantation. We estimated the magnitude of change in disability, depressive symptoms, and HRQL with hierarchical segmented linear mixed-effects models. Among 251 lung transplant recipients, 50 developed PGD Grade 3. Regardless of PGD severity, participants had improvements in disability and depressive symptoms, as well as generic-physical, generic-mental, respiratory-specific, and health-utility HRQL, exceeding 1- to 4-fold the minimally clinically important difference across all instruments. Participants with PGD Grade 3 had a lower magnitude of improvement in generic-physical HRQL and health-utility than in all other participants. Among participants with PGD Grade 3, prolonged mechanical ventilation was associated with greater attenuation of improvements. PGD remains a threat to the 2 primary aims of lung transplantation, extending survival and improving HRQL. Attenuation of improvement persists long after hospital discharge. Future studies should assess if interventions can mitigate the impact of PGD on patient-reported outcomes.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Validity and reliability of patient reported outcomes measurement information system computerized adaptive tests in systemic lupus erythematous.

BACKGROUND: The evaluation of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive test (CAT) in adults with systemic lupus erythematous (SLE) is an emerging field of research. We aimed to examine the test-retest reliability and construct validity of the PROMIS CAT in a Canadian cohort of patients with SLE. METHODS: Two hundred twenty-seven patients completed 14 domains of PROMIS CAT and seven legacy instruments during their clinical visits. Test-retest reliability of PROMIS was evaluated 7-10 days from baseline using intraclass correlation coefficient (ICC (2; 1)). The construct validity of the PROMIS CAT domains was evaluated against the commonly used legacy instruments, and also in comparison to disease activity and disease damage using Spearman correlations. A multitrait-multimethod matrix (MMM) approach was used to further assess construct validity comparing selected 10 domains of PROMIS and SF-36 domains. RESULTS: Moderate to excellent reliability was found for all domains (ICC [2;1] ranging from lowest, 0.66 for Sleep Disturbance and highest, 0.93 for the Mobility domain). Comparing seven legacy instruments with 14 domains of PROMIS CAT, moderate to strong correlations (0.51-0.91) were identified. The average time to complete all PROMIS CAT domains was 11.7 min. The MMM further established construct validity by showing moderate to strong correlations (0.55-0.87) between select PROMIS and SF-36 domains; the average correlations from similar traits (convergent validity) were significantly greater than the average correlations from different traits. CONCLUSIONS: These results provide evidence on the reliability and validity of PROMIS CAT in SLE in a Canadian cohort.

Benefits and promotion of physical activity in rheumatoid arthritis.

PURPOSE OF REVIEW: The aim of this article is to describe the benefits of physical activity and exercise on rheumatoid arthritis disease activity, functioning, and symptoms; and offer recommendations for promotion of physical activity and exercise among people with rheumatoid arthritis. RECENT FINDINGS: In addition to well-known benefits of exercise such as improving cardiovascular health and metabolic syndrome and reducing obesity, exercise has consistently shown rheumatoid arthritis-specific benefits. Exercise and increases in physical activity improve clinically measured disease activity, reduce symptoms such as fatigue and pain, and improve function and mental health. In spite of these benefits, most people with rheumatoid arthritis are inactive. Patient barriers to engaging in physical activity may include fears of joint damage, rheumatoid arthritis symptoms, and lack of understanding that physical activity improves the symptoms that may be barriers. However, the greatest barrier to healthy levels of physical activity among individuals with rheumatoid arthritis appears to be the lack of direction from healthcare providers. SUMMARY: Exercise is safe and highly beneficial for people with rheumatoid arthritis. Because receiving recommendations from healthcare providers may be the factor most strongly associated with engaging in physical activity or exercise, providers are encouraged to give patients positive messages about the benefits of physical activity and the extremely low risks of harm.

Frailty after lung transplantation is associated with impaired health-related quality of life and mortality.

BACKGROUND: Lung transplantation and related medications are associated with pathobiological changes that can induce frailty, a state of decreased physiological reserve. Causes of persistent or emergent frailty after lung transplantation, and whether such transplant-related frailty is associated with key outcomes, are unknown. METHODS: Frailty and health-related quality of life (HRQL) were prospectively measured repeatedly for up to 3 years after lung transplantation. Frailty, quantified by the Short Physical Performance Battery (SPPB), was tested as a time-dependent binary and continuous predictor. The association of transplant-related frailty with HRQL and mortality was evaluated using mixed effects and Cox regression models, respectively, adjusting for age, sex, ethnicity, diagnosis, and for body mass index and lung function as time-dependent covariates. We tested the association between measures of body composition, malnutrition, renal dysfunction and immunosuppressants on the development of frailty using mixed effects models with time-dependent predictors and lagged frailty outcomes. RESULTS: Among 259 adults (56% male; mean age 55.9±12.3 years), transplant-related frailty was associated with lower HRQL. Frailty was also associated with a 2.5-fold higher mortality risk (HR 2.51; 95% CI 1.21 to 5.23). Further, each 1-point worsening in SPPB was associated, on average, with a 13% higher mortality risk (HR 1.13; 95% CI 1.04 to 1.23). Secondarily, we found that sarcopenia, underweight and obesity, malnutrition, and renal dysfunction were associated with the development of frailty after transplant. CONCLUSIONS: Transplant-related frailty is associated with lower HRQL and higher mortality in lung recipients. Abnormal body composition, malnutrition and renal dysfunction may contribute to the development of frailty after transplant. Confirming the role of these potential contributors and developing interventions to mitigate frailty may improve lung transplant success.

Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease. METHODS: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed. RESULTS: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed. CONCLUSIONS: We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

Patient-reported flare frequency is associated with diminished quality of life and family role functioning in systemic lupus erythematosus.

PURPOSE: To understand the influence of the systemic lupus erythematosus (SLE)-related flares on patient's health-related quality of life (HRQoL). METHODS: An online survey included individuals with self-reported physician's diagnosis of SLE or lupus nephritis (LN). Lupus impact tracker (LIT) assessed lupus symptoms and HRQoL, SLE-Family questionnaire measured family role functioning, and Healthy Days Core Module (HDCM) measured overall mental and physical health. Chi-square and analysis of variance evaluated differences by flare frequency. Multivariable linear regression and generalized linear models evaluated the independent relationships of flare frequency to HRQoL. RESULTS: 1066 respondents with SLE or LN completed the survey. Mean (SD) duration of illness was 12.4 (10.1) years. 93.4% (n = 996) were women, 82.3% (n = 830) were White, and 49.7% (n = 530) were employed or students. More frequent flares were associated with significantly worse scores on all HRQoL measures: LIT (adjusted means: 0 flares, 31.8; 1-3 flares, 47.0; 4-6 flares, 56.1; ≥ 7 flares, 63.6; P < 0.001); SLE-Family (adjusted means: 0 flares, 3.1; 1-3 flares 3.8; 4-6 flares, 4.3; ≥ 7 flares, 4.6, P < 0.001); HDCM unhealthy days (0 flares, 8.7; 1-3 flares, 17.4; 4-6 flares, 21.5; ≥ 7 flares, 26.2 days, P < 0.001). CONCLUSION: Lupus flares contributed to impaired functional and psychological well-being, family functioning, and number of monthly healthy days. Better understanding of the burden of flare activity from the patient's perspective will support a holistic approach to lupus management.

Patient and clinician perspectives on a patient-facing dashboard that visualizes patient reported outcomes in rheumatoid arthritis.

BACKGROUND: Poor patient-clinician communication around patient-reported outcomes (PROs) is a barrier to the effective management of rheumatoid arthritis (RA). We aimed to develop an RA 'dashboard' that could facilitate conversations about PROs and that would be acceptable to a wide range of patients, including English and Spanish speakers and patients with adequate or limited health literacy. METHODS: A diverse group of RA patients along with clinicians from two academic rheumatology clinics joined separate focus groups. We solicited feedback and made iterative changes to mock-ups of an RA dashboard that visualized PROs using a human-centred design process. We used the thematic analysis method to identify and characterize themes from the focus groups and used these insights to refine the dashboard. RESULTS: We conducted six focus groups involving 25 RA patients and three groups with 11 clinicians. Patients and clinicians agreed that the dashboard could enhance communication about PROs and RA disease activity and could promote patient self-management. Patients varied in their (a) comprehension, (b) preferences for the display and features of the dashboard, and (c) desired uses for the dashboard. Clinicians expressed significant concerns about the logistics of using the dashboard in clinical practice. CONCLUSION: Using principles of human-centred design, we created an RA dashboard that was well-accepted among patients and clinicians. The ability to customize the data display is important for tailoring the dashboard to patients with diverse needs and preferences. Special attention should be given to feasibility concerns voiced by clinicians.