Barriers, Facilitators, and Preferences for Mental Health Services Among Patients With Systemic Lupus Erythematosus: A Qualitative Study.

OBJECTIVE: Although patients with systemic lupus erythematosus (SLE) experience high levels of depression and anxiety disorders, evidence concerning patient perceptions of facilitators and barriers to effective uptake of mental health services (eg, referral to therapists and psychiatrists, psychoeducational interventions, or support groups) is limited. METHODS: We conducted semistructured qualitative interviews with 15 adults with SLE to explore patient experiences and perceptions of mental health services to identify facilitators and barriers to accessing mental health care among patients with SLE. Qualitative interviews were conducted via telephone and audio recorded for transcription and directed content analysis using NVivo software by two coders. RESULTS: The median age of the 15 participants was 48 years, 87% were female, 33% identified as Black or African American, and 33% identified as Hispanic or Latino. Qualitative themes were organized into three domains: barriers, facilitators, and preferences for mental health services. Barriers to the use of mental health services include mental health stigma, sociodemographic factors, lack of autonomy, and time commitment. Facilitators to the use of mental health services included strong relationships with their rheumatologists and mental health care clinician experience with patients with SLE. Preferences for mental health services included education-based formats, mental health providers who work with patients with SLE, peer group formats, demographically and disease-matched psychological resources, and an emphasis on non-disease-related activities. CONCLUSION: In the setting of persistent unmet psychosocial needs of patients living with SLE, data from this qualitative study will inform the development and refinement of mental health interventions that bolster psychological wellbeing in the SLE population.

Posttraumatic Stress Disorder and Risk of Systemic Lupus Erythematosus Among Medicaid Recipients.

OBJECTIVE: We studied posttraumatic stress disorder (PTSD), a severe trauma-related mental disorder, and systemic lupus erythematosus (SLE) risk in a large, diverse population enrolled in Medicaid, a US government-sponsored health insurance program for low-income individuals. METHODS: We identified SLE cases and controls among patients ages 18-65 years enrolled in Medicaid for ≥12 months in the 29 most populated US states from 2007 to 2010. SLE and PTSD case statuses were defined based on validated patterns of International Classification of Diseases, Ninth Revision codes. Index date was the date of the first SLE code. Controls had no SLE codes but had another inpatient or outpatient code on the index date and were matched 1:10 to cases by age, sex, and race. Conditional logistic regressions calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association of PTSD with incident SLE, adjusting for smoking, obesity, oral contraceptive use, and other covariates. RESULTS: A total of 10,942 incident SLE cases were matched to 109,420 controls. The prevalence of PTSD was higher in SLE cases, at 10.74 cases of PTSD per 1,000 person-years (95% CI 9.37-12.31) versus 7.83 cases (95% CI 7.42-8.27) in controls. The multivariable-adjusted OR for SLE among those with PTSD was 2.00 (95% CI 1.64-2.46). CONCLUSION: In this large, racially and sociodemographically diverse US population, we found patients with a prior PTSD diagnosis had twice the odds of a subsequent diagnosis of SLE. Studies are necessary to clarify the mechanisms driving the observed association and to inform possible interventions.

The link between post-traumatic stress disorder and systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous, multisystem autoimmune disorder characterized by unpredictable disease flares. Although the pathogenesis of SLE is complex, an epidemiologic link between posttraumatic stress disorder (PTSD) and the development of SLE has been identified, suggesting that stress-related disorders alter the susceptibility to SLE. Despite the strong epidemiologic evidence connecting PTSD and SLE, gaps remain in our understanding of how the two may be connected. Perturbations in the autonomic nervous system, neuroendocrine system, and at the genomic level may cause and sustain immune dysregulation that could lower the threshold for the development and propagation of SLE. We first describe shared risk factors for SLE and PTSD. We then describe potential biological pathways which may facilitate excessive inflammation in the context of PTSD. Among those genetically predisposed to SLE, systemic inflammation that accompanies chronic stress may fan the flames of smoldering SLE by priming immune pathways. Further studies on the connection between trauma and inflammation will provide important data on pathogenesis, risk factors, and novel treatments for SLE.

Joint-Specific Memory and Sustained Risk for New Joint Accumulation in Autoimmune Arthritis.

OBJECTIVE: Inflammatory arthritides exhibit hallmark patterns of affected and spared joints, but in each individual, arthritis affects only a subset of all possible sites. The purpose of this study was to identify patient-specific patterns of joint flare to distinguish local from systemic drivers of disease chronicity. METHODS: Patients with juvenile idiopathic arthritis followed without interruption from disease onset into adulthood were identified across 2 large academic centers. Joints inflamed at each visit were established by medical record review. Flare was defined as physician-confirmed joint inflammation following documented inactive disease. RESULTS: Among 222 adults with JIA, 95 had complete serial joint examinations dating from disease onset in childhood. Mean follow-up was 12.5 years (interquartile range 7.9-16.7 years). Ninety (95%) of 95 patients achieved inactive disease, after which 81% (73 patients) experienced at least 1 flare. Among 940 joints affected in 253 flares, 74% had been involved previously. In flares affecting easily observed large joint pairs where only 1 side had been involved before (n = 53), the original joint was affected in 83% and the contralateral joint in 17% (P < 0.0001 versus random laterality). However, disease extended to at least 1 new joint in ~40% of flares, a risk that remained stable even decades after disease onset, and was greatest in flares that occurred while patients were not receiving medication (54% versus 36% of flares occurring with therapy; odds ratio 2.09, P = 0.015). CONCLUSION: Arthritis flares preferentially affect previously inflamed joints but carry an ongoing risk of disease extension. These findings confirm joint-specific memory and suggest that prevention of new joint accumulation should be an important target for arthritis therapy.

Implications of Evolving Disease Classification for Drug Approval in Juvenile Idiopathic Arthritis.

The classification of inflammatory arthritis incorporates a sharp divide between diseases of childhood onset, grouped together as juvenile idiopathic arthritis, and diseases such as rheumatoid arthritis that begin by definition in adulthood. An important consequence of this divide is that regulatory authorities and many rheumatologists regard pediatric and adult arthritides as truly different, with the implication that drugs should be evaluated separately for each category. However, it is now clear that most forms of arthritis transcend the pediatric/adult boundary and that agents generally exhibit comparable success irrespective of age of onset, offering new opportunities in drug development and regulation focused on pharmacology and safety rather than efficacy. This paradigm shift will enable advances in arthritis treatment, originating either with adults or children, to translate more rapidly across the age spectrum.

Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis.

T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.

Th1 polarization defines the synovial fluid T cell compartment in oligoarticular juvenile idiopathic arthritis.

Oligoarticular juvenile idiopathic arthritis (oligo JIA) is the most common form of chronic inflammatory arthritis in children, yet the cause of this disease remains unknown. To understand immune responses in oligo JIA, we immunophenotyped synovial fluid T cells with flow cytometry, bulk RNA-Seq, single-cell RNA-Seq (scRNA-Seq), DNA methylation studies, and Treg suppression assays. In synovial fluid, CD4+, CD8+, and γδ T cells expressed Th1-related markers, whereas Th17 cells were not enriched. Th1 skewing was prominent in CD4+ T cells, including Tregs, and was associated with severe disease. Transcriptomic studies confirmed a Th1 signature in CD4+ T cells from synovial fluid. The regulatory gene expression signature was preserved in Tregs, even those exhibiting Th1 polarization. These Th1-like Tregs maintained Treg-specific methylation patterns and suppressive function, supporting the stability of this Treg population in the joint. Although synovial fluid CD4+ T cells displayed an overall Th1 phenotype, scRNA-Seq uncovered heterogeneous effector and regulatory subpopulations, including IFN-induced Tregs, peripheral helper T cells, and cytotoxic CD4+ T cells. In conclusion, oligo JIA is characterized by Th1 polarization that encompasses Tregs but does not compromise their regulatory identity. Targeting Th1-driven inflammation and augmenting Treg function may represent important therapeutic approaches in oligo JIA.

Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis.

OBJECTIVE: Macrophage activation syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis (sJIA) characterised by a vicious cycle of immune amplification that can culminate in overwhelming inflammation and multiorgan failure. The clinical features of MAS overlap with those of active sJIA, complicating early diagnosis and treatment. We evaluated adenosine deaminase 2 (ADA2), a protein of unknown function released principally by monocytes and macrophages, as a novel biomarker of MAS. METHODS: We established age-based normal ranges of peripheral blood ADA2 activity in 324 healthy children and adults. We compared these ranges with 173 children with inflammatory and immune-mediated diseases, including systemic and non-systemic JIA, Kawasaki disease, paediatric systemic lupus erythematosus and juvenile dermatomyositis. RESULTS: ADA2 elevation beyond the upper limit of normal in children was largely restricted to sJIA with concomitant MAS, a finding confirmed in a validation cohort of sJIA patients with inactive disease, active sJIA without MAS or sJIA with MAS. ADA2 activity strongly correlated with MAS biomarkers including ferritin, interleukin (IL)-18 and the interferon (IFN)-γ-inducible chemokine CXCL9 but displayed minimal association with the inflammatory markers C reactive protein and erythrocyte sedimentation rate. Correspondingly, ADA2 paralleled disease activity based on serial measurements in patients with recurrent MAS episodes. IL-18 and IFN-γ elicited ADA2 production by peripheral blood mononuclear cells, and ADA2 was abundant in MAS haemophagocytes. CONCLUSIONS: These findings collectively identify the utility of plasma ADA2 activity as a biomarker of MAS and lend further support to a pivotal role of macrophage activation in this condition.

Older Adults' Recognition of Trade-Offs in Healthcare Decision-Making.

OBJECTIVES: To examine older persons' understanding of healthcare decision-making involving trade-offs. DESIGN: Cross-sectional survey. SETTING: Primary care clinics. PARTICIPANTS: Community-living persons aged 65 and older (N = 50). MEASUREMENTS: After being primed to think about trade-offs with a focus on chronic disease management, participants were asked to describe a decision they had made in the past involving a trade-off. If they could not, they were asked to describe a decision they might face in the future and were then given an example of a decision. They were also asked about communication with their primary care provider about their priorities when faced with a trade-off. RESULTS: Forty-four participants (88%) were able to describe a healthcare decision involving a trade-off; 25 provided a decision in the past, 17 provided a decision they might face in the future, and two provided a future decision after hearing an example. One participant described a nonmedical decision, and two participants described goals without providing a trade-off. Of the healthcare decisions, 26 involved surgery, seven were end-of life decisions, seven involved treatment of chronic disease, and four involved chemotherapy. When asked whether their providers should know their health outcome priorities, 44 (88%) replied yes, and 35 (70%) believed their providers knew their priorities, but only 18 (36%) said that they had had a specific conversation about priorities. CONCLUSION: The majority of participants were able to recognize the trade-offs involved in healthcare decision-making and wanted their providers to know their priorities regarding the trade-offs. Despite being primed to think about the trade-offs involved in day-to-day treatment of chronic disease, participants most frequently described episodic, high-stakes decisions including surgery and end-of-life care.

Relationship between universal health outcome priorities and willingness to take medication for primary prevention of myocardial infarction.

OBJECTIVES: To determine how well universal health outcome priorities represent individuals' preferences in specific clinical situations. DESIGN: Observational cohort study. SETTING: Community. PARTICIPANTS: Community-dwelling adults aged 65 and older (N = 357). MEASUREMENTS: Participants used three tools assessing universal health outcome priorities related to two common trade-offs: quality versus quantity of life and future health versus present inconveniences and burdens of treatment. The tools' ability to identify participants who were unwilling to take a medication that reduced the risk of myocardial infarction but caused dizziness and fatigue was analyzed. RESULTS: There were consistent and significant associations between unwillingness to take the medication and prioritizing quality of life or future health for all three tools in the expected direction (P < .05). Despite these associations, the positive (PPV) and negative predictive values for the tools were generally modest (0.49-0.83). The tool with the most specific statements resembling the medication scenario had the best specificity (0.97) and PPV (0.83). CONCLUSION: Universal health outcome priorities only modestly identified older persons who would be unwilling to take a medication for primary prevention of myocardial infarction that causes adverse effects. Although tools that are the most general in their assessment of priorities have the benefit of being applicable across the widest range of scenarios, tools with greater specificity may be necessary to inform individual treatment decisions.

Considering the balance: development of a scale to assess patient views on trade-offs in competing health outcomes.

OBJECTIVES: To describe the development of a scale assessing participant attitudes regarding two commonly encountered trade-offs: quality versus quantity of life and present versus future health. DESIGN: Observational cohort study. SETTING: Community. PARTICIPANTS: Three hundred and fifty-seven community-dwelling adults aged 65 and older. MEASUREMENTS: An initial set of 20 items rated on a 5-point Likert scale of agreement was reduced using principal components analysis. Construct validity was evaluated through comparison of the scale with other tools addressing the same trade-offs and analysis of participant characteristics associated with attitudes favoring quality over quantity of life and present over future health. Internal consistency was assessed using Cronbach alpha. Test-retest reliability was assessed using intraclass correlation coefficients (ICCs). RESULTS: The scale consists of two subscales, each addressing one trade-off, with a total of 10 items. All factor loadings were 0.5 and greater, and subscale scores were significantly different (P ≤ .05) in the expected directions when comparing with other tools and with participant race, education, and religious identity. Internal consistency was good (Cronbach α 0.85 and 0.84), and test-retest reliability was fair (ICCs 0.63 and 0.47). Subscale score medians fell near the middle of each scale, with narrow interquartile ranges, but more than 15% of the sample scored at an extreme of each subscale. CONCLUSION: This new scale captures views on two common trade-offs in health care. Although test-retest reliability was modest, its high validity suggests that this tool can be used to familiarize people with common trade-offs and further explore influences on attitudes.

How to ask: older adults' preferred tools in health outcome prioritization.

OBJECTIVE: To assess older adults' attitudes toward eliciting health outcome priorities. METHODS: This observational cohort study of 356 community-living adults age ≥65 included three tools: (1) Health Outcomes: ranking four outcomes (survival, function, freedom from pain, and freedom from other symptoms); (2) Now vs. Later: rating importance of current versus future quality of life; (3) Attitude Scale: agreement with statements about health outcomes and current versus future health. RESULTS: Whereas 41% preferred Health Outcomes, 40% preferred the Attitude Scale. Only 7-12% rated any tool as very hard or hard. In bivariate analysis, participants of non-white race and with lower education, health literacy, and functional status were significantly more likely to rate at least one of the tools as easy (p < .05). Across all tools, 17% of participants believed tools would change care. The main reason for thinking there would be no change was satisfaction with existing care (62%). CONCLUSIONS: There is variability in how older persons wish to be asked about health outcome priorities. Few find this task difficult, and difficulty was not greater among participants with lower health literacy, education, or health status. PRACTICE IMPLICATIONS: By offering different tools, healthcare providers can help patients clarify their health outcome priorities.