Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events.

Importance: The prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated. Objective: To determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population. Design, Setting, and Participants: This cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti-beta-2 glycoprotein I [aß2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023. Main Outcomes and Measures: Associations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons. Results: Among the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aß2GPI IgM (63 [2.6%]), and aß2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aß2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aß2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aß2GPI IgA negatively correlated with cholesterol efflux capacity (r = -0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aß2GPI IgA-positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1. Conclusions and Relevance: In this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aß2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

Therapeutic recreation camps for youth with childhood-onset systemic lupus erythematosus: perceived psychosocial benefits.

BACKGROUND: The psychosocial burden of having a chronic disease can be substantial for adolescents with childhood-onset systemic lupus erythematosus (cSLE). Current literature is scarce on interventions that can improve psychosocial outcomes for this population. Therapeutic recreation camps have been proposed as a beneficial experience for chronically ill pediatric populations. However, their effective components have not been well characterized in patients with cSLE. In this study, we sought to understand the various components of the camp experience for adolescents with cSLE from both the patient and parent perspective. METHODS: We recruited patients with cSLE who had participated in one or more annual, weekend-long recreational lupus camp(s) near Dallas, Texas. Semi-structured in-depth telephone interviews were conducted from March-June 2020 with both the patients and parents. Questions focused on overall patient experience, psychosocial impact of camp participation, coping skills gained, and opportunities to prepare for the transition from pediatric to adult care. Interviews were coded and analyzed using inductive thematic analysis. RESULTS: We interviewed 9 current and former campers (ages 16-24), including a current camp counselor, and 3 of their parents separately. Reported benefits included a positive impact on social support through peer bonding, opportunities to develop coping mechanisms through structured activities and peer/medical staff interactions, opportunities for education about the cSLE disease experience, improved adherence through peer modeling, overall increase in self-efficacy, and better parental insight into the patient experience. Participants also provided suggestions for expansion and improvement in program development to optimize educational opportunities for both campers and parents. In addition, they advocated for longitudinal social support and community building. CONCLUSIONS: In this qualitative study, in which cSLE patients and their parents reflected on their experiences with therapeutic recreation camps, we found several perceived benefits impacting the patient and parent experience. Participants expressed a desire for more educational opportunities that could contribute to their successful transition from pediatric to adult care. Further studies are needed to demonstrate the effects of therapeutic recreation camps on the psychosocial health of this population.

Health Literacy and Patient Activation in the Pediatric to Adult Transition in Systemic Lupus Erythematosus: Patient and Health Care Team Perspectives.

OBJECTIVE: To identify perceived health literacy (HL) and patient activation (PA) needs during the transition from pediatric to adult rheumatology among patients with childhood-onset systemic lupus erythematosus (cSLE). METHODS: Semistructured interviews of patients and health care professionals were conducted from November 2019 through May 2020, until thematic saturation was achieved. Interviews were audio-recorded, transcribed, coded, and analyzed using thematic analysis. RESULTS: Thirteen post-transition adult female participants with cSLE were recruited from a public safety-net hospital system or from private practice. Thirteen health care team members were recruited from two pediatric and four adult rheumatology clinical sites serving patients in the same metropolitan area. Patients and health care team members acknowledged numerous HL components as important to transition, including language fluency, education, SLE-specific knowledge, self-efficacy, and accurate knowledge of personal medical history. Our interviews found PA to be an important component of the transition process, driven by internalization of the implications of cSLE diagnosis, self-education, autonomy, introspection, and trustworthy doctor-patient relationships. Patients valued access to their online electronic medical record, recommended multimodal SLE-specific education materials, and desired increased access to social workers. Health care team members stressed the importance of early preparation for transition and use of mobile medical applications and endorsed interventions such as lupus camp and increased partnership with psychologists and social workers. CONCLUSION: HL and PA are perceived by patients and health care team members as substantially influencing transition success. Further research is needed to evaluate whether interventions to improve HL and PA positively influence cSLE transition outcomes.

A Medical Records Review Study Assessing Safety of Zoster Vaccine Recombinant, Adjuvanted in Patients With Rheumatic Disease.

OBJECTIVE: Patients with rheumatic disease are at increased risk for herpes zoster infection. Because of limited safety data in this population and concerns over vaccine-precipitated flares, there are no guidelines for vaccination with the zoster vaccine recombinant, adjuvanted (ZRA). We evaluated self-reported adverse events (AEs) and disease activity after ZRA administration in adults with rheumatic disease. METHODS: In this medical records review study at our large academic center, patients who had received at least 1 dose of ZRA from January 1, 2018 to March 11, 2020 were assessed. Self-reported AEs and disease activity were monitored 3 months after each ZRA administration. Measures of disease activity were reviewed 6 months before ZRA in those who received both doses, or 3 months before ZRA in those who received 1 dose. RESULTS: We identified 65 patients, of whom 34 (52.3%) received both doses of ZRA. Four patients (6.2%) self-reported AEs after receiving ZRA, all of which were minor and systemic. Three patients (9.2%) developed a flare after receiving ZRA, compared with 8 (12.3%) who experienced a flare in the baseline period. There was no significant change in flare incidence or disease activity after vaccination. Subgroup analysis of those on biologic and nonbiologic disease-modifying antirheumatic drugs revealed no differences in frequency of postvaccination AEs, flares, or disease activity. CONCLUSIONS: In our cohort, disease activity seemed stable when comparing disease markers before and after ZRA administration. In addition, ZRA was well-tolerated with minor AEs. Further studies are needed to guide formal vaccination recommendations.

"You Just Have to Keep Going, You Can't Give Up": Coping mechanisms among young adults with lupus transferring to adult care.

INTRODUCTION: Coping mechanisms and emotional regulation are important contributors to psychosocial health during stressful life events. We sought to describe the coping and emotional responses of persons with childhood-onset systemic lupus erythematosus during the transfer from pediatric to adult healthcare. METHODS: Semi-structured in-depth one-on-one interviews were conducted with 13 young women aged 18-24 of minority background who had transferred to adult care in a public hospital system. Thematic analysis was used to identify themes motifs from the data. RESULTS: Participants described the use of (1) problem-focused coping such as the use of clear communication and self-education, (2) adaptive emotion-focused coping such as cognitive reframing and acceptance, (3) social coping including support-seeking, (4) meaning-making coping including positive religious framing and viewing events as learning opportunities for growth, and (5) disengaged coping including denial and social isolation. A range of emotional responses associated with the transfer were described including fear, anger, loss, and feelings of empowerment and excitement. CONCLUSION: Effective coping and emotional regulation are modifiable factors that may impact transfer-related outcomes and psychosocial health. Addressing coping mechanisms is relevant to the optimized transfer to adult care.

Predictors of Adverse outcomes in patients with systemic lupus erythematosus transitioning to adult care.

BACKGROUND: The transition from pediatric to adult care is a vulnerable period for individuals with chronic diseases. We sought to identify risk factors associated with poor outcomes in patients with childhood-onset systemic lupus erythematosus (cSLE) who have transitioned to adult care. METHODS: A retrospective analysis of cSLE patients was performed. Outcomes of interest were development of end-stage renal disease (ESRD) or death and time to first hospitalization following final pediatric rheumatology visit. Multivariable logistic and Cox regression models were used. RESULTS: Of 190 patients with cSLE, 21 (11%) developed ESRD and 9 (5%) died following the final pediatric rheumatology visit. In logistic regression, public insurance, history of Child Protective Services involvement, and an unscheduled hospitalization during the final year in pediatric care were predictive of ESRD or death (odds ratio (95% confidence intervals (CI)) 6.7 (1.5-30.7), 6.6 (2.3-19.1), and 3.2 (1.3-8.3), respectively). Among 114 patients with healthcare utilization data, 53% had a hospitalization in adult care. In Cox regression analysis, a pediatric outpatient opioid prescription was associated with shorter time to adult hospitalization and White or Asian race was associated with longer time to adult hospitalization (hazard ratio (CI) 3.5 (1.7-7.0) and 0.1 (0.03-0.4), respectively). CONCLUSIONS: Risks factors associated with poor outcomes in adult care amongst patients with cSLE include public insurance, history of Child Protective Services involvement, unscheduled care utilization in pediatric care, pediatric outpatient opioid prescription, Black race and Hispanic ethnicity. Efforts to improve long-term outcomes among patients with cSLE should focus on these populations.

Time to First Completed Visit and Health Care Utilization Among Young Adults Transferring From Pediatric to Adult Rheumatologic Care in a Safety-Net Hospital.

OBJECTIVE: The transfer from pediatric to adult care for young adults is a vulnerable period. Our objectives were to quantify the time between the final pediatric and the first adult visit and to evaluate unscheduled utilization in care and progression to end-stage renal disease (ESRD) or death. METHODS: We conducted a retrospective analysis of pediatric patients transferring to a large adult rheumatology clinic. Outcomes included time to first completed adult visit, unscheduled health care utilization (hospitalizations and emergency department [ED] visits), and progression to ESRD or death. Multivariable regression models assessed variables predictive of outcomes of interest. RESULTS: A total of 141 pediatric patients who transferred care were identified: 77% female, 65% Hispanic, and 60% with connective tissue diseases (CTDs). The mean time between final pediatric and first completed adult rheumatology visit was 221 days (range 0-1,207 days). In regression modeling, we found that continued insurance coverage, younger age at referral, and referral from a pediatric rheumatologist were predictive of shorter time to completed adult visit (P < 0.005). Factors associated with hospitalizations and ED visits included CTD diagnosis and Black race (odds ratio [OR] 8.54 [95% confidence interval (95% CI) 1.84-39.58] and 3.04 [95% CI 1.02-9.12] for hospitalizations and OR 3.6 [95% CI 1.59-8.14] and 6.0 [95% CI 1.60-22.69] for ED visits, respectively). ESRD or death occurred among 15% of patients with a CTD. CONCLUSION: In pediatric patients transferring to an adult rheumatology clinic, continued insurance coverage and referral from a pediatric rheumatologist decreased delays in attending an adult visit; CTD and Black race were associated with high rates of unscheduled health care utilization.

Clinical Team Perspectives on the Psychosocial Aspects of Transition to Adult Care for Patients With Childhood-Onset Systemic Lupus Erythematosus.

OBJECTIVE: The transition from pediatric to adult care for youth with childhood-onset systemic lupus erythematosus (SLE) is a vulnerable period. Adverse outcomes during this transition include gaps in care, unscheduled health care utilization, loss of insurance, and high disease activity. The objective of this study was to examine the clinical care teams' perspective on the psychosocial factors associated with transition outcomes, which are poorly understood in this population. METHODS: We conducted in-depth interviews with clinical care team members who interact with childhood-onset SLE patients during transfer from pediatric to adult rheumatology. A semistructured interview guide was used to prompt participants' perspectives about the psychosocial factors associated with the transition process for patients with childhood-onset SLE. Audio recordings were transcribed and analyzed using the constant comparative method. We stopped conducting interviews once thematic saturation was achieved. RESULTS: Thirteen in-depth interviews were conducted. Participants included pediatric rheumatologists (n = 4), adult rheumatologists from both academic and private practice settings (n = 4), nurses (n = 2), a nurse practitioner, a social worker, and a psychologist. We identified several themes deemed by clinical care teams as important during the transition, including the impact of the family, patient resilience and coping mechanisms, the role of mental health and emotional support, and the need for education, peer support, and social connectedness. CONCLUSION: We identified several psychosocial themes that clinical team members believe impact the transition of patients with childhood-onset SLE into adult care. The role of parental modeling, youth resilience, mental health and emotional care, improved childhood-onset SLE education, and structured peer support and social connectedness are highlighted, which may be amenable to interventions.

Ethnic Disparities in Atherosclerotic Cardiovascular Disease Incidence and Prevalence Among Rheumatoid Arthritis Patients in the United States: a Systematic Review.

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased atherosclerotic cardiovascular disease (ASCVD). General population cohorts have shown African American individuals to have greater and Hispanic Americans to have lower cardiovascular disease prevalence when compared with non-Hispanic white individuals; however, the reasons for these findings are not clear. This systematic review seeks to describe the incidence and prevalence of ASCVD stratified by race/ethnicity within the US RA population. METHODS: MEDLINE, Embase, and Cochrane databases were searched for studies that reported incidence or prevalence of ASCVD (including, but not limited to, fatal and nonfatal stroke, myocardial infarction, and cardiovascular death) in those with RA. Abstracts and full texts were screened separately for inclusion by two reviewers, with a third reviewer to resolve discrepancies. RESULTS: We screened 2625 abstracts and fully reviewed 138 manuscripts. Twenty-one were included that cited at a minimum the percentage of non-Hispanic whites in their population. No publication meeting entry criteria initially stratified ASCVD by race/ethnicity. The average prevalent ASCVD in RA is 46.9% (95% CI: 46.8-47) (range of prevalent ASCVD: 30%-47%). The average incident ASCVD is 8.2% (95% CI: 8.14-8.25) (range of incident ASCVD 1%-46%). CONCLUSION: In this systematic review, we found a paucity of data on racially/ethnically diverse RA patients and ASCVD outcomes. Future studies should report the prevalence of ASCVD in various races/ethnicities with RA in the United States. These data would help inform clinicians on how best to manage cardiovascular disease risk in RA.

SARS-CoV-2 Antibody Responses Do Not Predict COVID-19 Disease Severity.

OBJECTIVES: Initial reports indicate adequate performance of some serology-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assays. However, additional studies are required to facilitate interpretation of results, including how antibody levels impact immunity and disease course. METHODS: A total of 967 subjects were tested for IgG antibodies reactive to SARS-CoV-2, including 172 suspected cases of SARS-CoV-2, 656 plasma samples from healthy donors, 49 sera from patients with rheumatic disease, and 90 specimens from individuals positive for polymerase chain reaction (PCR)-based respiratory viral panel. A subgroup of SARS-CoV-2 PCR-positive cases was tested for IgM antibodies by proteome array method. RESULTS: All specificity and cross-reactivity specimens were negative for SARS-CoV-2 IgG antibodies (0/795, 0%). Positive agreement of IgG with PCR was 83% of samples confirmed to be more than 14 days from symptom onset, with less than 100% sensitivity attributable to a case with severe immunosuppression. Virus-specific IgM was positive in a higher proportion of cases less than 3 days from symptom onset. No association was observed between mild and severe disease course with respect to IgG and IgM levels. CONCLUSIONS: The studied SARS-CoV-2 IgG assay had 100% specificity and no adverse cross-reactivity. Measures of IgG and IgM antibodies did not predict disease severity in our patient population.

Inflammatory myositis in systemic lupus erythematosus.

BACKGROUND: The coexistence of inflammatory myositis in systemic lupus erythematosus (SLE) has not been extensively studied. In this study, we describe the incidence, distinct types of inflammatory myositis, and risk factors for this finding in a cohort of pediatric and adult SLE patients. METHODS: We identified SLE patients with coexisting myositis followed between 2010 and 2019 at two pediatric hospitals and one adult hospital. Demographic, clinical, laboratory, and pathological features of myositis were collected, and descriptive statistics were applied. RESULTS: A total of 1718 individuals were identified as having SLE (451 pediatric and 1267 adult patients). Of these, 108 were also diagnosed with inflammatory myositis (6.3%). People of black race had a significantly higher prevalence of inflammatory myositis, as did those with childhood-onset SLE compared to adult-onset disease. In the majority of patients (68%), SLE and inflammatory myositis presented concurrently. Overlapping features of systemic sclerosis occurred in 48%, while dermatomyositis-specific rashes were present in a third. Arthralgias and inflammatory arthritis were seen in >90%. Thrombotic events and significant pregnancy-related morbidity were present in more than a third of patients. Lymphopenia, hypocomplementemia, and a positive RNP were the most common laboratory features noted. Myositis-specific antibodies (MSA) and myositis-associated antibodies (MAA) were present in >40% of patients. A review of 28 muscle biopsy reports revealed a wide array of pathological features, including nonspecific changes, dermatomyositis, polymyositis, and necrotizing auto-immune myopathy. CONCLUSION: In our SLE patient population, 6.3% presented with concurrent inflammatory myositis. Dermatomyositis-specific rashes, clinical features of systemic sclerosis, arthralgias and arthritis, and cytopenias were common coexisting clinical manifestations. A high frequency of RNP, MSA, and MAA were found. People of black race and with childhood-onset disease had a higher prevalence of myositis. Our findings suggest that SLE patients of black race, with childhood-onset SLE, and who possess MSA or MAA should be routinely screened for myositis.

Advocacy 101: Engaging Rheumatology Fellows in Health Policy and Advocacy.

OBJECTIVE: Rheumatology fellowship programs lack formal curricular content to educate trainees about legislative and regulatory health care policies that have a profound impact on academic and community practices. Advocacy 101 was created as a program to address this gap and engage fellows-in-training (FIT) in health advocacy efforts. METHODS: A web-based survey was sent via the American College of Rheumatology (ACR) FIT listserve in July 2015 and April 2016. The survey queried respondents about their knowledge of and participation in health policy and advocacy. Survey results guided the design of an educational program called Advocacy 101 for FIT and program directors in conjunction with the ACR Advocates for Arthritis fly-in meeting. RESULTS: The survey response rate increased from 19% in 2015 (95 of 500 FIT) to 39% in 2016 (231 of 595 FIT). In 2015, the top reason for nonparticipation in health policy and advocacy efforts (64% of respondents) was lack of knowledge on how to get involved. This reason decreased to 39% of respondents in 2016. Other barriers to participation included lack of time and familiarity with the issues. Over the 2 years, FIT identified patient access to medication and insurance, and physician reimbursement as important advocacy issues. All participants of Advocacy 101 reported an increase in knowledge of health policy and the intent to stay involved. CONCLUSION: FIT regard health policy issues as important, but many are uncertain of how to participate in advocacy. Advocacy 101 is the first program designed to educate and engage rheumatology FIT in health policy and advocacy endeavors.

Body Mass Index, Weight Loss, and Cause-Specific Mortality in Rheumatoid Arthritis.

OBJECTIVE: To examine associations of body mass index (BMI) and weight loss with cause-specific mortality in rheumatoid arthritis (RA). METHODS: A cohort of US veterans with RA was followed until death or through 2013. BMI was categorized as underweight, normal, overweight, and obese. Weight loss was calculated as the 1) annualized rate of change over the preceding 13 months, and 2) cumulative percent. Vital status and cause of death were obtained from the National Death Index. Multivariable competing-risks regression models were utilized to assess the time-varying associations of BMI and weight loss with cause-specific mortality. RESULTS: Among 1,600 participants and 5,789 patient-years of followup, 303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The highest weight-loss rate and weight-loss percent were associated with a higher risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27 [95% confidence interval (95% CI) 1.61-3.19]; percent: sHR 2.31 [95% CI 1.06-5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11-5.01]; percent: sHR 1.90 [95% CI 1.00-3.62]). Overweight BMI was protective of cardiovascular mortality (sHR 0.59 [95% CI 0.38-0.91]), while underweight BMI was associated with a near 3-fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28-6.67]). Incorporation of time-varying BMI and weight loss in the same models did not substantially alter individual associations for cardiovascular and cancer mortality, but an association between weight-loss percentage and respiratory mortality was attenuated after BMI adjustment. CONCLUSION: Both BMI and weight loss are predictors of cause-specific mortality in RA. Weight loss is a strong predictor of cardiovascular and cancer mortality, while underweight BMI is a stronger predictor of respiratory mortality.

Vascular calcifications on hand radiographs in rheumatoid arthritis and associations with autoantibodies, cardiovascular risk factors and mortality.

OBJECTIVE: To examine whether vascular calcifications on hand films in RA might aid in determining mortality risk. METHODS: Hand radiographs from 906 RA patients were scored as positive or negative for vascular calcifications. Patient characteristics associated with vascular calcifications were assessed using multivariable logistic regression, and associations with mortality were examined using Cox proportional hazards regression. Cytokines and multiplex ACPA were measured in both groups. RESULTS: A total of 99 patients (11%) demonstrated radiographic vascular calcifications. Factors independently associated with vascular calcifications included diabetes [odds ratio (OR) 2.85; 95% CI 1.43, 5.66], cardiovascular disease at enrolment (OR 2.48; 95% CI 1.01, 6.09), prednisone use (OR 1.90; 95% CI 1.25, 2.91), current smoking (OR 0.06; 95% CI 0.01, 0.23) and former smoking (OR 0.36; 95% CI 0.27, 0.48) vs never smoking. In cytokine and ACPA subtype analysis, IL-4 and anti-citrullinated apolipoprotein E were significantly increased in patients with vascular calcifications in fully adjusted multivariable models. After multivariable adjustment, vascular calcifications were associated with an increase in all-cause mortality (hazard ratio 1.41; 95% CI 1.12, 1.78; P = 0.004). CONCLUSION: Vascular calcifications on hand radiographs were independently associated with increased all-cause mortality in RA. Mechanisms underpinning the associations of IL-4 and select ACPA with vascular calcifications and their utility as biomarkers predictive of cardiovascular disease risk in RA merit further study.