The impact of alternative arrangements, contingent jobs, and work secured through an app on the well-being of working age adults: Results from the California Work and Health Survey.

BACKGROUND: There is recognition of the growing prevalence of alternative work arrangements, contingent jobs, and work secured through an app. However, there have been few systematic efforts to understand the impact of these forms of work on individuals and households. METHODS: The data derive from the California Work and Health Survey administered to a sample of the working age population of the state solicited through random-digit dialing of cell phone numbers. 4014 individuals completed the survey, 26% of those with an in-service cell phone number. We present odds ratios and 95% confidence intervals from logistic regression estimating the impact of being an independent contractor, in other forms of alternative work arrangements, in contingent jobs, and in work secured through an app, on economic and health status and working conditions in main jobs, with and without adjustment for covariates. RESULTS: Several of the forms of work analyzed are associated with lower earnings and higher rates of wage theft, household poverty, benefit recipiency, and expectation of hardships in food, housing, and medical care in the immediate future. Association between the forms of work and current health status is less consistent. However, several forms of work are associated with working conditions known to be risk factors for subsequent health problems. CONCLUSIONS: Public policy to mitigate the adverse impacts of work, largely developed in the 20th Century when there was an identified workplace, may be insufficient to protect workers' well-being for alternative work arrangements, contingent jobs, and work secured through an app.

Dusty trades and associated rheumatoid arthritis in a population-based study in the coal mining counties of Appalachia.

OBJECTIVES: We previously showed increased coal mining-associated risk of rheumatoid arthritis (RA). Using additional survey data, we sought to delineate this risk further. METHODS: We used data from two cross-sectional, random-digit-dial, population-based surveys (males;≥50 years) in selected counties in the Appalachian region of the inland, mid-Atlantic USA with elevated pneumoconiosis mortality. Surveys ascertained age, smoking, coal mining and non-coal silica exposure jobs. In a subset, we surveyed ergonomic exposures, scored by intensity. We queried diagnosis of RA, corticosteroid use, and, in a subset, use of disease modifying antirheumatic drugs (DMARDs). Multivariable logistic regression modelled RA risk (defined by glucocorticoid or DMARDs use) associated with coal mining employment, other silica exposure, smoking status, and age and ergonomic exposures. RESULTS: We analysed data for 2981 survey respondents (mean age 66.6 years; 15% current, 44% ex-smokers). The prevalence of glucocorticoid-treated and DMARD-treated RA was 11% and 4%, respectively. Glucocorticoid-treated RA was associated with coal mining (OR 3.5; 95% CI 2.5 to 4.9) and non-coal mining silica exposure (OR 3.2; 95% CI 2.4 to 4.4). For DMARD-treated RA, the odds associated with coal mining and other silica remained elevated: OR 2.3 (95% CI 1.18, 4.5) and OR 2.7 (95% CI 1.51, 5.0), respectively. In the same model, the highest intensity ergonomic exposure also was associated with increased odds of RA (OR 4.3; 95% CI 1.96 to 9.6). CONCLUSIONS: We observed a strong association between coal mining and other silica-exposing dusty trades and RA. Clinicians and insurers should consider occupational histories in the aetiology of RA.

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.

Mortality Among Minority Populations with Systemic Lupus Erythematosus, Including Asian and Hispanic/Latino Persons - California, 2007-2017.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with manifestations that vary widely in severity. Although minority populations are at higher risk for SLE and have more severe outcomes (1), population-based estimates of mortality by race and ethnicity are often lacking, particularly for Asian and Hispanic/Latino persons. Among 812 patients in the California Lupus Surveillance Project (CLSP) during 2007-2009 (2,3), who were matched to the 2007-2017 National Death Index (NDI), 16.6% had died by 2017. This proportion included persons of White (14.4%), Black (25%), Asian (15.3%), and Hispanic/Latino (15.5%) race/ethnicity. Standardized mortality ratios (SMRs) of observed-to-expected deaths among persons with SLE within each racial/ethnic group were 2.3, 2.0, 3.8, and 3.9, respectively. These findings provide the first population-based estimates of mortality among Asian and Hispanic/Latino persons with SLE. Coordination of robust care models between primary care providers and rheumatologists could ensure that persons with SLE receive a timely diagnosis and appropriate treatments that might help address SLE-associated mortality.

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.

Individualized decision aid for diverse women with lupus nephritis (IDEA-WON): A randomized controlled trial.

BACKGROUND: Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. METHODS AND FINDINGS: In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet (n = 147), participants randomized to the decision aid (n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% (p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% (p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% (p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. CONCLUSIONS: An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02319525.

Correction to: Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety.

The given and family name of a co-author R. Adams Dudley was swapped in the published article. The correct given name is R. Adams and the family name is Dudley.

Serum biomarkers of inflammation and muscle strength among women with systemic lupus erythematosus.

OBJECTIVES: Muscle strength is an important determinant of physical function in women with systemic lupus erythematosus (SLE). Serum biomarkers of inflammation, including interleukin-6 (IL-6) and C-Reactive Protein (CRP), are associated with differences in muscle strength among individuals without rheumatologic disease. We examined whether serum levels of IL-6 and CRP are associated with upper and lower extremity muscle strength among adult women with SLE. METHODS: One hundred thirty-six women with SLE participated in this cross-sectional study. High-sensitivity CRP was analyzed by nephelometry. IL-6 serum levels were analyzed by high sensitivity enzyme-linked immunosorbent assay. Upper and lower extremity muscle strength were assessed by grip strength and peak torque of knee extension and flexion, respectively. Regression analyses modeled associations of CRP and IL-6 with upper and lower extremity muscle strength controlling for age, SLE duration, physical activity, prednisone use, BMI, plaquenil use, and pain. RESULTS: Higher serum levels of IL-6 and CRP were associated with significantly weaker upper and lower extremity muscle strength even when controlling for covariates. CONCLUSIONS: Increased serum IL-6 and CRP are associated with clinically significant differences in upper and lower extremity muscle strength and may be useful in identifying those at risk for weakness and decreased physical function.

Interest in initiating an early phase clinical trial: results of a longitudinal study of advanced cancer patients.

OBJECTIVE: Enhanced recruitment of patients with advanced cancer (ACP) to early phase (EP) trials is needed. However, selective recruitment may affect the kinds of patients who are recruited. To address whether ACP who initiate EP trial enrollment differ from those who do not, we prospectively surveyed ACP well in advance of potential trial recruitment and followed them over time to identify those who initiated the recruitment process. METHODS: EP trial initiation was defined as a patient being referred for screening to an active EP trial. Depression and anxiety were assessed with the Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder Scale (GAD-7), respectively. Demographic and disease characteristics, functional status, and patient preferences regarding decision making were examined as possible predictors of EP trial initiation. RESULTS: Of the 78 advanced cancer patients in the cohort studied, 21 (27%) initiated EP trial participation, while 57 (73%) did not. Of those who initiated this process, 14 (67%) went on to enroll in an EP study. Level of depression severity was associated with EP trial initiation, with rates of initiation nearly three times higher (35% vs. 12%, p = 0.054) among patients with minimal to mild levels of depression compared to those with moderate or higher levels of depression. EP trial initiation was not associated with demographic or socioeconomic variables, cancer type, functional status, quality of life, or decision-making variables. CONCLUSIONS: The presence of elevated depressive symptoms may be associated with the EP trial recruitment and enrollment processes. This possible relationship warrants further study. Copyright © 2016 John Wiley & Sons, Ltd.

What advanced cancer patients with limited treatment options know about clinical research: a qualitative study.

PURPOSE: Discussions between oncologists and advanced cancer patients (ACPs) may touch on the complex issue of clinical trial participation. Numerous initiatives have sought to improve the quality of these potentially difficult conversations. However, we have limited data about what ACPs know about clinical research as they enter such discussions as, to date, such research has focused on the period following informed consent. This study examines ACPs' understanding of clinical research in the treatment period before consent. METHODS: We conducted in-depth interviews with adult ACPs with limited treatment options at four clinics in an academic medical center. So as not to influence patients' perspectives, interviewers probed patients' knowledge of clinical research only if the patient first brought up the topic. Interviews (40-60 min) were audio-recorded, transcribed, and analyzed thematically and via quantitative content analysis by an interdisciplinary team. RESULTS: Of 78 patients recruited, 56 (72%) spontaneously brought up the topic of clinical research during interview and are included in this analysis. Qualitative thematic analysis and quantitative content analysis revealed that patients' knowledge varied in terms of (1) accuracy and (2) specificity (level of detail). ACPs who spoke with high specificity were not always accurate, and ACPs with accurate knowledge included both high- and low-specificity speakers. CONCLUSIONS: ACPs' knowledge of clinical research is variable. Patients who can discuss the technical details of their care may or may not understand the broader purpose and procedures of clinical trials. Understanding this variability is important for improving patient-provider communication about clinical research and supporting efforts to provide individualized care for ACPs.

Hydroxychloroquine dosing in immune-mediated diseases: implications for patient safety.

Evidence suggests that hydroxychloroquine (HCQ) retinal toxicity is more common than previously thought. Adhering to careful weight-based dosing can significantly reduce the risk of this adverse event and is recommended in recent guidelines. We used electronic health record data from a large health system to examine HCQ dosing over a 5-year period and identify risk factors associated with higher dosage of HCQ. We constructed a longitudinal, retrospective cohort of patients with HCQ prescriptions (1681 patients with 3490 prescribing events) between 2012 and 2016. We measured HCQ dosing patterns relative to guidelines (<6.5 and <5.0 mg/kg) over time and used longitudinal multivariate mixed effects logistic regression to identify sociodemographic, clinical and health system factors associated with receiving higher than recommended doses of HCQ. The proportion of patients receiving doses above 6.5 mg/kg decreased from 12% in 2012 to 7% by 2016. Similarly, the proportion of patients with doses above 5.0 mg/kg fell from 38% in 2012 to 30% in 2016. Low body weight (<68 kg) was strongly associated with receiving doses of HCQ above 6.5 mg/kg across all time points, even after adjusting for other factors (odds ratios ranging from 13.2 to 21.0). Although the proportion of patients receiving higher than recommended HCQ doses has declined over a period of 5 years, a substantial number of individuals remain at increased risk for toxicity. Given the widespread use of HCQ in immune-mediated diseases, our study suggests that interventions aimed to ensure appropriate dosing are warranted to improve patient safety.

Annual average ambient particulate matter exposure estimates, measured home particulate matter, and hair nicotine are associated with respiratory outcomes in adults with asthma.

BACKGROUND: While exposure to outdoor particulate matter (PM) has been associated with poor asthma outcomes, few studies have investigated the combined effects of outdoor and indoor PM (including secondhand tobacco smoke). OBJECTIVE: To examine the associations between PM and asthma outcomes. METHODS: We analyzed data from a cohort of adults with asthma and rhinitis (n=302; 82% both conditions; 13% asthma only; 5% rhinitis alone) including measures of home PM, tobacco smoke exposure (hair nicotine and self-report), ambient PM from regional monitoring, distance to roadway, and season (wet or dry). The outcomes of interest were frequent respiratory symptoms and forced expiratory volume in 1 second (FEV1) below the lower limit of normal (NHANES reference values). Multivariable regression analyses examined the associations (Odds Ratio [OR] and 95% Confidence Interval [95%CI]) between exposures and these outcomes, adjusted by sociodemographic characteristics. RESULTS: In adjusted analyses of each exposure, the highest tertile of home PM and season of interview were associated with increased odds for more frequent respiratory symptoms (OR=1.64 95%CI: [1.00, 2.69] and OR=1.66 95%CI: [1.09, 2.51]). The highest tertile of hair nicotine was significantly associated with FEV1 below the lower limit of normal (OR=1.80 95%CI: [1.00, 3.25]). In a model including home PM, ambient PM, hair nicotine, and season, only two associations remained strong: hair nicotine with FEV1 below the lower limit of normal and season of measurement (dry, April-October) with increased respiratory symptoms (OR=1.85 95%CI: [1.00, 3.41] and OR=1.54 95%CI: [1.0, 2.37]). When that model was stratified by sex, the highest tertiles of ambient PM and hair nicotine were associated with FEV1 below the lower limit of normal among women (OR=2.23 95%CI: [1.08, 4.61] and OR=2.90 95%CI: [1.32, 6.38]), but not men. The highest tertile of hair nicotine was also associated with increased respiratory symptoms in women but not men (OR=2.38 95%CI: [1.26, 4.49]). When stratified by age, the middle quartile of ambient PM and the highest hair nicotine tertile were associated with increased respiratory symptoms (OR=2.07 95%CI: [1.01, 4.24] and OR=2.55 95%CI: [1.21, 5.36]) in those under 55 but not in the older stratum. CONCLUSIONS: Exposure to PM from both home and ambient sources is associated with increased symptoms and lower lung function in adults with asthma, although these associations vary by type of PM, the respiratory outcome studied, sex and age.

The design of a low literacy decision aid about rheumatoid arthritis medications developed in three languages for use during the clinical encounter.

BACKGROUND: Shared decision-making in rheumatoid arthritis (RA) care is a priority among policy makers, clinicians and patients both nationally and internationally. Demands on patients to have basic knowledge of RA, treatment options, and details of risk and benefit when making medication decisions with clinicians can be overwhelming, especially for those with limited literacy or limited English language proficiency. The objective of this study is to describe the development of a medication choice decision aid for patients with rheumatoid arthritis (RA) in three languages using low literacy principles. METHODS: Based on the development of a diabetes decision aid, the RA decision aid (RA Choice) was developed through a collaborative process involving patients, clinicians, designers, decision-aid and health literacy experts. A combination of evidence synthesis and direct observation of clinician-patient interactions generated content and guided an iterative process of prototype development. RESULTS: Three iterations of RA Choice were developed and field-tested before completion. The final tool organized data using icons and plain language for 12 RA medications across 5 issues: frequency of administration, time to onset, cost, side effects, and special considerations. The tool successfully created a conversation between clinician and patient, and garnered high acceptability from clinicians. CONCLUSIONS: The process of collaboratively developing an RA decision aid designed to promote shared decision making resulted in a graphically-enhanced, low literacy tool. The use of RA Choice in the clinical encounter has the potential to enhance communication for RA patients, including those with limited health literacy and limited English language proficiency.

Positive psychosocial factors may protect against perceived stress in people with systemic lupus erythematosus with and without trauma history.

OBJECTIVE: Trauma history is associated with SLE onset and worse patient-reported outcomes; perceived stress is associated with greater SLE disease activity. Stress perceptions vary in response to life events and may be influenced by psychosocial factors. In an SLE cohort, we examined whether stressful events associated with perceived stress, whether psychosocial factors affected perceived stress, and whether these relationships varied by prior trauma exposure. METHODS: This is a cross-sectional analysis of data from the California Lupus Epidemiology Study, an adult SLE cohort. Multivariable linear regression analyses controlling for age, gender, educational attainment, income, SLE damage, comorbid conditions, glucocorticoids ≥7.5 mg/day and depression examined associations of recent stressful events (Life Events Inventory) and positive (resilience, self-efficacy, emotional support) and negative (social isolation) psychosocial factors with perceived stress. Analyses were stratified by lifetime trauma history (Brief Trauma Questionnaire (BTQ)) and by adverse childhood experiences (ACEs) in a subset. RESULTS: Among 242 individuals with SLE, a greater number of recent stressful events was associated with greater perceived stress (beta (95% CI)=0.20 (0.07 to 0.33), p=0.003). Positive psychosocial factor score representing resilience, self-efficacy and emotional support was associated with lower perceived stress when accounting for number of stressful events (-0.67 (-0.94 to -0.40), p<0.0001); social isolation was associated with higher stress (0.20 (0.14 to 0.25), p<0.0001). In analyses stratified by BTQ trauma and ACEs, associations of psychosocial factors and perceived stress were similar between groups. However, the number of recent stressful events was significantly associated with perceived stress only for people with BTQ trauma (0.17 (0.05 to 0.29), p=0.0077) and ACEs (0.37 (0.15 to 0.58), p=0.0011). CONCLUSION: Enhancing positive and lessening negative psychosocial factors may mitigate deleterious perceived stress, which may improve outcomes in SLE, even among individuals with a history of prior trauma who may be more vulnerable to recent stressful events.

Screening of Environmental Chemicals to Characterize Exposures in Participants With Systemic Lupus Erythematosus.

OBJECTIVE: There is a need to characterize exposures associated with the pathogenesis of systemic lupus erythematosus (SLE). In this pilot study, we explore a hypothesis-free approach that can measure thousands of exogenous chemicals in blood ("exposome") in patients with SLE and unaffected controls. METHODS: This cross-sectional study analyzed a cohort of patients with prevalent SLE (n = 285) and controls (n = 106). Plasma was analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). Mass spectrometry features present in at least 25% of all samples were selected for association analysis (n = 2,737). Features were matched to potential chemicals using available databases. Association analysis of abundances of features with SLE status was performed, adjusting for age and sex. We also explored features associated with SLE phenotypes, sociodemographic factors, and current medication use. RESULTS: We found 30 features significantly associated with SLE status (Bonferroni P < 0.05). Of these, seven matched chemical names based on databases. These seven features included phthalate metabolites, a formetanate metabolite, and eugenol. The abundance of acid pesticides differed between patients with SLE and controls (Bonferroni P < 0.05). Two unmatched features were associated with a history of lupus nephritis, and one with anti-double-stranded DNA antibody production (Bonferroni P < 0.05). Seventeen features varied by self-reported race and ethnicity, including a polyfluoroalkyl substance (analysis of variance P < 1.69 × 10-5). Eleven features correlated with antimalarials, 6 with mycophenolate mofetil, and 29 with prednisone use. CONCLUSION: This proof-of-concept study demonstrates that LC-QTOF/MS is a powerful tool that agnostically detects circulating exogenous compounds. These analyses can generate hypotheses of disease-related exposures for future prospective, longitudinal studies.

Mediators of the socioeconomic gradient in outcomes of adult asthma and rhinitis.

OBJECTIVES: We estimated the extent to which socioeconomic status (SES) gradients in adult asthma and rhinitis outcomes can be explained by home and neighborhood environmental factors. METHODS: Using survey data for 515 adults with either asthma or rhinitis, or both, we examined environmental mediators of SES associations with disease severity, using the Severity of Asthma Scale, and health-related quality of life (HRQL), using the Rhinasthma Scale. We defined SES on the basis of education and household income. Potential environmental mediators included home type and ownership, exposures to allergens and irritants, and a summary measure of perceived neighborhood problems. We modeled each outcome as a function of SES, and controlled for age, gender, and potential mediators. RESULTS: Gradients in SES were apparent in disease severity and HRQL. Living in a rented house partially mediated the SES gradient for both severity and HRQL (P < .01). Higher perceived levels of neighborhood problems were associated with poorer HRQL and partially mediated the income-HRQL relationship (P < .01). CONCLUSIONS: Differences in home and neighborhood environments partially explained associations of SES with adult asthma and rhinitis outcomes.

European genetic ancestry is associated with a decreased risk of lupus nephritis.

OBJECTIVE: African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. METHODS: This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. RESULTS: Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10(-30) ). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB1*0301 and DRB1*1501) did not substantively alter this relationship. CONCLUSION: European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors.

Higher environmental relative moldiness index values measured in homes of adults with asthma, rhinitis, or both conditions.

Higher values of the environmental relative moldiness index (ERMI), a DNA-based method for quantifying indoor molds, have been associated with asthma in children. In this study, settled dust samples were collected from the homes of adults with asthma, rhinitis, or both conditions (n=139 homes) in Northern California. The ERMI values for these samples were compared to those from dust collected in homes from the same geographic region randomly selected as part of the 2006 American Healthy Home Survey (n=44). The median ERMI value in homes of adult with airway disease (6) was significantly greater than median ERMI value (2) in the randomly selected homes (p<0.0001). In this study in Northern California, the homes of adults with asthma had ERMI values consistent with a heavier burden of indoor mold than that measured in other homes from the same region.

Race, Ethnicity, and Disparities in the Risk of End-Organ Lupus Manifestations Following a Systemic Lupus Erythematosus Diagnosis in a Multiethnic Cohort.

OBJECTIVE: Data on the onset of lupus manifestations across multiple organ domains and in diverse populations are limited. The objective was to analyze racial and ethnic differences in the risk of end-organ lupus manifestations following systemic lupus erythematosus (SLE) diagnosis in a multiethnic cohort. METHODS: The California Lupus Epidemiology Study (CLUES) is a longitudinal study of SLE. Data on major end-organ lupus manifestations were collected and categorized by organ system: renal, hematologic, neurologic, cardiovascular, and pulmonary. Multiorgan disease was defined as manifestations in ≥2 of these distinct organ systems. Kaplan-Meier curves assessed end-organ disease-free survival, and Cox proportional hazards regression estimated the rate of end-organ disease following SLE diagnosis, adjusting for age at diagnosis, sex, and self-reported race and ethnicity (White, Hispanic, Black, and Asian). RESULTS: Of 326 participants, 89% were female; the mean age was 45 years. Self-reported race and ethnicity were 30% White, 23% Hispanic, 11% Black, and 36% Asian. Multiorgan disease occurred in 29%. Compared to White participants, Hispanic and Asian participants had higher rates, respectively, of renal (hazard ratio [HR] 2.9 [95% confidence interval (95% CI) 1.8-4.7], HR 2.9 [95% CI 1.9-4.6]); hematologic (HR 2.7 [95% CI 1.3-5.7], HR 2.1 [95% CI 1.0-4.2]); and multiorgan disease (HR 3.3 [95% CI 1.8-5.9], HR 2.5 [95% CI 1.4-4.4]) following SLE diagnosis. CONCLUSION: We found heightened risks of developing renal, hematologic, and multiorgan disease following SLE diagnosis among Hispanic and Asian patients with SLE, as well as a high burden of multiorgan disease among CLUES participants.