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.

Physical Activity Associates With Lower Systemic Inflammatory Gene Expression in Rheumatoid Arthritis.

OBJECTIVE: While general population studies have shown inverse associations between physical activity and common inflammatory biomarkers, the effects of physical activity on inflammatory gene expression and signaling pathways in rheumatoid arthritis (RA) remain unknown. We aimed to determine whether physical activity independently associates with expression of inflammatory genes among people with RA. METHODS: This was a prospective observational study of adults with RA. Physical activity was measured by quantitative actigraphy over 7 consecutive days, and peripheral blood collected during the same time period was used for RNA sequencing followed by differential gene expression, pathway, and network analyses. RESULTS: Actigraphy and RNA sequencing data were evaluated in 35 patients. The cohort had a mean age of 56 (SD 12) years, and was 91% female, 31% White, 9% Black, 9% Asian, and 40% Hispanic. We found 767 genes differentially expressed (adjusted P < 0.1) between patients in the greatest vs lowest physical activity tertiles, after adjusting for sex, age, race, and ethnicity. The most active patients exhibited dose-dependent downregulation of several immune signaling pathways implicated in RA pathogenesis. These included CD40, STAT3, TREM-1, interleukin (IL)-17A, IL-8, Toll-like receptor, and interferon (IFN) signaling pathways. Upstream cytokine activation state analysis predicted reduced activation of tumor necrosis factor-α and IFN in the most active group. In sensitivity analyses, we adjusted for RA disease activity and physical function and found consistent results. CONCLUSION: Patients with RA who were more physically active had lower expression of immune signaling pathways implicated in RA pathogenesis, even after adjusting for disease activity, suggesting that physical activity may confer a protective effect in RA.

Physical Inactivity and Incident Depression in a Multiracial, Multiethnic Systemic Lupus Erythematosus Cohort.

OBJECTIVE: Physical activity is known to improve depressive symptoms. The present study was undertaken to examine physical inactivity as a predictor of incident depression in systemic lupus erythematosus (SLE). METHODS: Data derive from the California Lupus Epidemiology Study (CLUES), a longitudinal cohort with confirmed SLE diagnoses. Physical inactivity was assessed from a single item, "I rarely or never do any physical activities," and depressive symptoms by the 8-item Patient Health Questionnaire (PHQ-8). Analysis included those not depressed at baseline (PHQ-8 score <10) who completed an in-person baseline assessment and at least 1 follow-up visit (n = 225). Incident depression was defined as a PHQ-8 score of ≥10 at follow-up. Cox proportional hazards regression modeled incident depression over 2 years as a function of baseline physical inactivity, controlling for age, sex, race, income, comorbidities, disease activity, and disease damage. RESULTS: At baseline, the mean ± SD age of the participants was 45 ± 15 years, 88% were female, and 70% identified as non-White. Mean PHQ scores for those without depression at baseline did not differ by activity status, but those who were inactive at baseline were significantly more likely to develop depression over the next 2 years (hazard ratio [HR] 2.89 [95% confidence interval (95% CI) 1.46-5.71]). After adjusting for covariates, the association remained strong, including a >3-fold increased risk of incident depression among the sedentary group (HR 3.88 [95% CI 1.67-9.03]). CONCLUSION: In this diverse SLE cohort, a simple question about physical inactivity was highly predictive of incident depression over the subsequent 2 years. Results suggest an urgent need for approaches to reduce sedentary behavior in this high-risk population.

Increased rates of secondary bacterial infections, including Enterococcus bacteremia, in patients hospitalized with coronavirus disease 2019 (COVID-19).

OBJECTIVE: We compared the rates of hospital-onset secondary bacterial infections in patients with coronavirus disease 2019 (COVID-19) with rates in patients with influenza and controls, and we investigated reports of increased incidence of Enterococcus infections in patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: An academic quaternary-care hospital in San Francisco, California. PATIENTS: Patients admitted between October 1, 2019, and October 1, 2020, with a positive SARS-CoV-2 PCR (N = 314) or influenza PCR (N = 82) within 2 weeks of admission were compared with inpatients without positive SARS-CoV-2 or influenza tests during the study period (N = 14,332). METHODS: National Healthcare Safety Network definitions were used to identify infection-related ventilator-associated complications (IVACs), probable ventilator-associated pneumonia (PVAP), bloodstream infections (BSIs), and catheter-associated urinary tract infections (CAUTIs). A multiple logistic regression model was used to control for likely confounders. RESULTS: COVID-19 patients had significantly higher rates of IVAC and PVAP compared to controls, with adjusted odds ratios of 4.7 (95% confidence interval [CI], 1.7-13.9) and 10.4 (95 % CI, 2.1-52.1), respectively. COVID-19 patients had higher incidence of BSI due to Enterococcus but not BSI generally, and whole-genome sequencing of Enterococcus isolates demonstrated that nosocomial transmission did not explain the increased rate. Subanalyses of patients admitted to the intensive care unit and patients who required mechanical ventilation revealed similar findings. CONCLUSIONS: COVID-19 is associated with an increased risk of IVAC, PVAP, and Enterococcus BSI compared with hospitalized controls, which is not fully explained by factors such as immunosuppressive treatments and duration of mechanical ventilation. The mechanism underlying increased rates of Enterococcus BSI in COVID-19 patients requires further investigation.

Obesity is Independently Associated With Worse Patient-Reported Outcomes in Women with Systemic Lupus Erythematosus.

OBJECTIVE: To determine whether obesity in women with systemic lupus erythematosus (SLE) is independently associated with worse patient-reported outcomes (PROs). METHODS: Data were derived from a prospective study of adult women with a diagnosis of SLE that was verified by medical record review. Two established definitions for obesity were used: fat mass index (FMI) ≥13 kg/m2 and body mass index (BMI) ≥30 kg/m2 . Dependent variables included 4 validated PROs: disease activity as assessed by the Systemic Lupus Activity Questionnaire (SLAQ), depressive symptoms as assessed by the Center for Epidemiologic Studies Depression Scale (CES-D), pain as assessed by the Short Form 36 (SF-36) pain subscale, and fatigue as assessed by the SF-36 vitality subscale. We used multivariable linear regression to evaluate the associations of obesity with PROs, while controlling for potential confounders (age, race, education, income, smoking, disease duration, disease damage, and prednisone use). RESULTS: The analysis included 148 participants, 32% of whom were obese. In the multivariate regression model, obesity was associated with worse scores for each PRO. Mean adjusted scores for the SLAQ and CES-D comparing obese versus non-obese participants were 14.8 versus 11.5 (P = 0.01) and 19.8 versus 13.1 (P < 0.01), respectively. The obese group also reported worse mean adjusted scores for pain (38.7 versus 44.2; P < 0.01) and fatigue (39.6 versus 45.2; P = 0.01). CONCLUSION: In a representative sample of women with SLE, obesity (as defined by both FMI and BMI) was independently associated with worse PROs, including disease activity, depressive symptoms, and symptoms of pain and fatigue. Obesity may represent a modifiable target for improving outcomes among obese women with SLE.

Pneumocystis jirovecii pneumonia (PJP) prophylaxis patterns among patients with rheumatic diseases receiving high-risk immunosuppressant drugs.

INTRODUCTION/OBJECTIVES: Pneumocystis jirovecii pneumonia (PJP) is a rare but potentially fatal opportunistic infection; however, consensus varies around which conditions or medications confer a level of risk sufficient to justify antibiotic prophylaxis for PJP. We used electronic health record (EHR) data to assess the current patterns of PJP prophylaxis, PJP outcomes, and prophylaxis-related adverse events among patients with rheumatic diseases who were receiving high-risk immunosuppressant drugs. METHODS: Data derive from the EHR of a large health system. We included new immunosuppressant users with diagnoses of vasculitis, myositis, or systemic lupus erythematosus. We calculated the proportion of patients who received PJP prophylaxis for each diagnosis and drug combination. We also calculated the number of PJP infections and the number of antibiotic adverse drug events (ADEs) per patient-year of exposure. RESULTS: We followed 316 patients for 23.2 + /- 14.2 months. Overall, 124 (39%) of patients received prophylactic antibiotics for PJP. At least 25% of patients with the highest risk conditions (e.g. vasculitis) or highest risk immunosuppressants (e.g. cyclophosphamide) did not receive PJP prophylaxis. We found no cases of PJP infection over 640 patient-years of follow up, including among those not receiving prophylaxis, and an overall incidence rate of ADEs of 2.2% per patient-year. CONCLUSIONS: PJP prophylaxis for patients with rheumatic conditions is inconsistent, with one quarter of patients who have high risk conditions or high risk immunosuppressants not receiving prophylaxis. However, given extremely low rates of PJP infection, but detectable ADEs to prophylactic antibiotics, our findings suggest that evidence to guide more personalized risk assessments are needed to inform PJP prophylaxis.

Discordance of the Framingham cardiovascular risk score and the 2013 American College of Cardiology/American Heart Association risk score in systemic lupus erythematosus and rheumatoid arthritis.

Despite the increasing use of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular (CV) risk score in clinical practice, few studies have compared this score to the Framingham risk score among rheumatologic patients. We calculated Framingham and 2013 ACC/AHA risk scores in subjects with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and assessed demographic, CV, and rheumatologic characteristics associated with discordant scores (high-risk ACC/AHA scores but low-risk Framingham scores). SLE and RA subjects drawn from two population-based cohort studies were assessed during in-person study visits. We used chi-squared tests and t tests to examine the association of discordant CV risk scores with baseline characteristics. Eleven (7.0%) of 157 SLE subjects and 11 (11.5%) of 96 RA subjects had discordant CV risk scores with high ACC/AHA scores and low Framingham scores. These findings did not significantly change when a 1.5 multiplier was applied to the Framingham score. Rheumatologic disease duration, high-sensitivity CRP levels, African-American race, diabetes, current use of anti-hypertensive medication, higher age, and higher systolic blood pressure were each significantly associated with discordant risk scores. Approximately 10% of SLE and RA subjects had discordant 10-year CV risk scores. Our findings suggest that the use of the 2013 ACC/AHA risk score could result in changes to lipid-lowering therapy recommendations in a significant number of rheumatologic patients. Prospective studies are needed to compare which score better predicts CV events in rheumatologic patients, especially those with risk factors associated with discordant risk scores.

Central Nervous System Manifestations of Systemic Lupus Erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a variety of phenomena. Manifestations are focal or diffuse, and correlate with disease mechanisms. Recent understanding of the contribution of blood-brain barrier dysfunction to the passage of circulating antineuronal antibodies into the brain parenchyma has shed light on pathogenesis. Correct attribution of neuropsychiatric manifestations to SLE remains a challenge, but validated attribution models will help. Diagnosis relies on characteristic clinical manifestations, SLE disease activity, antibody measurements, cerebrospinal fluid findings, specific neuroimaging findings, and exclusion of alternative etiologies. Current treatment encompasses the identification and management of the inciting event, symptomatic treatment, and anticoagulation or immunosuppression.

Neuromyelitis Optica.

Neuromyelitis optica (NMO), formerly known as Devic disease, is an autoimmune astrocytopathic disease characterized by transverse myelitis and optic neuritis. Most patients demonstrate a relapsing course with incomplete recovery between attacks, resulting in progressive disability. The pathogenesis involves production of aquaporin-4 antibodies (AQP4-IgG) by plasmablasts in peripheral circulation, disruption of the blood-brain barrier, complement-mediated astrocyte injury, and secondary demyelination. The diagnosis relies on characteristic clinical manifestations in the presence of serum AQP4-IgG positivity or specific neuroimaging findings, and exclusion of alternative etiologies. Current treatment involves aggressive immunosuppression with pulse-dose steroids during acute attacks and long-term immunosuppression for attack prevention.

Sociocultural factors affecting uptake of home-based neonatal thermal care practices in Africa: A qualitative review.

Neonatal hypothermia is a major contributor to neonatal mortality in sub-Saharan Africa, often as a comorbidity of severe infections, preterm births or asphyxia. Simple, cost-effective thermal care practices (TCPs) immediately at birth and in the post-natal period are recommended in the World Health Organization 'warm chain'. Current practices are suboptimal in the home in low-resource settings, where approximately half of neonatal deaths occur. Several databases (PubMed, OVID SP, Web of Science, The Cochrane Library and Google Scholar) were searched for original research on home-based TCPs. Seventeen articles were identified, and the results were analysed using a 'thermal care behavioural model'. This review of the qualitative literature on home-based practices across Africa illuminates the sociocultural factors affecting the uptake of recommended practices and strategies for behaviour change. Findings from the review confirm that potentially harmful cultural norms and traditions influence the sequence of TCPs in different contexts across Africa. Furthermore, caregiver factors and contextual barriers or facilitating factors to TCPs and behaviour change exist. Hypothermia and home-based TCPs are areas for further research. Thermal care behaviour change interventions tailored to the sociocultural context are necessary to improve neonatal outcomes in Africa.