Effects of genetically predicted posttraumatic stress disorder on autoimmune phenotypes.

Observational studies suggest that posttraumatic stress disorder (PTSD) increases risk for various autoimmune diseases. Insights into shared biology and causal relationships between these diseases may inform intervention approaches to PTSD and co-morbid autoimmune conditions. We investigated the shared genetic contributions and causal relationships between PTSD, 18 autoimmune diseases, and 3 immune/inflammatory biomarkers. Univariate MiXeR was used to contrast the genetic architectures of phenotypes. Genetic correlations were estimated using linkage disequilibrium score regression. Bi-directional, two-sample Mendelian randomization (MR) was performed using independent, genome-wide significant single nucleotide polymorphisms; inverse variance weighted and weighted median MR estimates were evaluated. Sensitivity analyses for uncorrelated (MR PRESSO) and correlated horizontal pleiotropy (CAUSE) were also performed. PTSD was considerably more polygenic (10,863 influential variants) than autoimmune diseases (median 255 influential variants). However, PTSD evidenced significant genetic correlation with nine autoimmune diseases and three inflammatory biomarkers. PTSD had putative causal effects on autoimmune thyroid disease (p = 0.00009) and C-reactive protein (CRP) (p = 4.3 × 10-7). Inferences were not substantially altered by sensitivity analyses. Additionally, the PTSD-autoimmune thyroid disease association remained significant in multivariable MR analysis adjusted for genetically predicted inflammatory biomarkers as potential mechanistic pathway variables. No autoimmune disease had a significant causal effect on PTSD (all p values > 0.05). Although causal effect models were supported for associations of PTSD with CRP, shared pleiotropy was adequate to explain a putative causal effect of CRP on PTSD (p = 0.18). In summary, our results suggest a significant genetic overlap between PTSD, autoimmune diseases, and biomarkers of inflammation. PTSD has a putative causal effect on autoimmune thyroid disease, consistent with existing epidemiologic evidence. A previously reported causal effect of CRP on PTSD is potentially confounded by shared genetics. Together, results highlight the nuanced links between PTSD, autoimmune disorders, and associated inflammatory signatures, and suggest the importance of targeting related pathways to protect against disease and disability.

Joint effects of one year of marine omega-3 fatty acid supplementation and participant dietary fish intake upon circulating lipid mediators of inflammation resolution in a randomized controlled trial.

OBJECTIVES: We assessed the joint effects of omega (n)-3 fatty acid supplementation and dietary fish intake on systemic lipid mediators of inflammation among adults. METHODS: Within VITAL, a double-blind randomized controlled trial, adults were randomized to ω-3 fatty acids (460 mg EPA + 380 mg DHA/d) or placebo. We selected participants who reported low (<1 serving/mo) baseline dietary fish intake and matched them by age, sex, race, and trial arm to participants with self-reported highest fish intake (≥3.9 servings/wk). Baseline and 1-y plasma samples were tested for 9 ω-3 fatty acid-derived lipid mediators. Multivariable linear models assessed lipid mediator changes and joint effects of ω-3 fatty acid supplementation and dietary fish intake. RESULTS: Forty-eight participants with low baseline fish intake were matched to 48 with high fish intake. Mean age was 64.6 (±7.26), 50% were female, and 85% non-Hispanic white. One-year lipid mediator changes in expected directions were observed in those receiving ω-3 fatty acids versus placebo: reductions in proinflammatory mediators, PGD2, 5-HETE, and 12-HETE; increases in proresolving mediators, EPA and DHA. Larger 1-y lipid biomarker changes were seen in those with low baseline fish intake randomized to active ω-3 fatty acids for DHA, EPA, PGD2, Resolvin D1, and Resolvin D4 were observed, although no significant multiplicative interactions were detected. DISCUSSION: Beneficial changes in circulating proresolving and proinflammatory mediators were found with 1-y of ω-3 fatty acid supplementation versus placebo for all participants, with a trend toward larger effects among those with low baseline fish intake, although interactions were not significant.

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.

Racial and Ethnic Composition of Populations Served by Freestanding Children's Hospitals and Disparities in Outcomes of Pediatric Lupus.

OBJECTIVE: Health disparities may be driven by hospital-level factors. We assessed whether racial and ethnic composition of populations hospitals serve explain or modify disparities in hospital outcomes of children with systemic lupus erythematosus (SLE). METHODS: In this retrospective cohort study of patients 5 to 26 years old with SLE at 47 children's hospitals in the Pediatric Health Information System (2006-2021), race and ethnicity were assessed at the patient level and hospital level (proportion of total admissions composed of Black or Hispanic patients, respectively). Outcomes included intensive care unit (ICU) admission or adverse renal outcome (end-stage renal disease, dialysis, or transplant) during follow-up. We estimated racial and ethnic disparities, adjusted or stratified by hospital racial or ethnic composition. RESULTS: Of 8,125 patients with SLE, 2,293 (28%) required ICU admission, and 698 (9%) had an adverse renal outcome. Black and non-Hispanic White disparities in ICU admission were observed only at hospitals serving higher proportions of Black patients (odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.04-1.59 vs OR 1.07, 95% CI 0.83-1.38). Larger Black and non-Hispanic White disparities in adverse renal outcomes were observed at hospitals with higher Black racial composition (OR 2.0, 95% CI 1.4-2.8 vs OR 1.7, 95% CI 1.1-2.4). Conversely, Hispanic versus non-Hispanic disparities in renal outcomes persisted after adjustment for hospital-reported Hispanic ethnic composition but were observed only at hospitals with lower proportions of Hispanic patients. CONCLUSION: Worse Black and White disparities in SLE outcomes are observed at children's hospitals serving more Black children, whereas distinct patterns are observed for Hispanic and non-Hispanic disparities. Reporting of hospital characteristics related to populations served is needed to identify modifiable drivers of hospital-level variation.

Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: In the 5.3-year randomized, 2 × 2 factorial, double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.61-0.99). Omega-3 (n-3) fatty acid supplementation showed a statistically nonsignificant reduction (HR 0.85, 95% CI 0.67-1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with two years of postintervention observation. METHODS: Of the 12,786 men aged ≥50 and 13,085 women aged ≥55 initially randomized, we observed surviving and willing participants for two more years. We continued to confirm annual participant-reported new AD by medical record review. Cox models calculated HRs for all confirmed incident AD, (and secondary endpoints, including probable cases, and individual ADs), during the observational and randomized periods. RESULTS: A total of 21,592 participants (83.5%) were observed for two more years; 514 participants developed incident confirmed AD (236 since prior report), of whom 255 had been randomized to vitamin D versus 259 to vitamin D placebo (HR 0.98 [95% CI 0.83-1.17] at 7 years). AD was confirmed in 234 participants initially randomized to n-3 fatty acids versus 280 randomized to its placebo (HR 0.83 [95% CI 0.70-0.99] at 7 years). Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results as follows: HR 0.85 (95% CI 0.70-1.04) for vitamin D and HR 0.87 (95% CI 0.71-1.06) for n-3 fatty acids. CONCLUSION: Two years after trial termination, the protective effects of 2000 IU/day of vitamin D dissipated, but 1,000 mg/day of n-3 fatty acids had a sustained effect in reducing AD incidence.

Posttraumatic stress disorder symptoms in systemic autoimmune rheumatic disease patients during the early COVID-19 pandemic.

AIM: Given reports of increased prevalence of PTSD symptoms at COVID-19 pandemic onset, we aimed to assess the prevalence of posttraumatic stress disorder (PTSD) symptoms at pandemic onset in individuals with and without systemic autoimmune rheumatic disease (SARD). METHODS: In May 2020, we invited 6678 patients to complete the Brief Trauma Questionnaire and the Posttraumatic Stress Disorder Checklist (PCL-5), validated PTSD symptom screenings. We compared responses from patients with and without SARD using multivariable logistic regression. RESULTS: We received 1473 responses (22% response rate) from 5/2020 to 9/2021 (63 with prior PTSD diagnoses, 138 with SARD history). The SARD population was more female (p .0001) and had a higher baseline prevalence of stress disorders (56% vs. 43%, p .004). SARD subjects reported more experiences with life-threatening illness, 60%, versus 53% among those without SARD (p .13), and more antidepressant or anxiolytic medication use pre-pandemic (78% vs. 59%, p .0001). Adjusting for pre-pandemic PTSD diagnosis, younger age and history of stress disorder were the most significant predictors of PCL-5 positivity. There were no significant differences in PCL-5 score or positivity among those with or without SARD. CONCLUSION: In this population, patients with SARD had a higher pre-COVID-19 prevalence of stress-related conditions, but it was not the case that they had an increased risk of PTSD symptoms in the early pandemic. Younger individuals, those with baseline depression, anxiety, or adjustment disorders, and those taking antidepressant or anxiolytic medications were more likely to have PTSD symptoms in the first waves of the COVID-19 pandemic.

Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.

Genome-Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases.

Background Patients with rheumatoid arthritis (RA) have a 2- to 10-fold increased risk of cardiovascular disease (CVD), but the biological mechanisms and existence of causality underlying such associations remain to be investigated. We aimed to investigate the genetic associations and underlying mechanisms between RA and CVD by leveraging large-scale genomic data and genetic cross-trait analytic approaches. Methods and Results Within UK Biobank data, we examined the genetic correlation, shared genetics, and potential causality between RA (Ncases=6754, Ncontrols=452 384) and cardiovascular diseases (CVD, Ncases=44 238, Ncontrols=414 900) using linkage disequilibrium score regression, cross-trait meta-analysis, and Mendelian randomization. We observed significant genetic correlations of RA with myocardial infarction (rg:0.40 [95% CI, 0.24-0.56), angina (rg:0.42 [95% CI, 0.28-0.56]), coronary heart diseases (rg:0.41 [95% CI, 0.27-0.55]), and CVD (rg:0.43 [95% CI, 0.29-0.57]) after correcting for multiple testing (P<0.05/5). When stratified by frequent use of analgesics, we found increased genetic correlation between RA and CVD among participants without aspirin usage (rg:0.54 [95% CI, 0.30-0.78] for angina; Pvalue=6.69×10-6) and among participants with paracetamol usage (rg:0.75 [95% CI, 0.20-1.29] for myocardial infarction; Pvalue=8.90×10-3), whereas others remained similar. Cross-trait meta-analysis identified 9 independent shared loci between RA and CVD, including PTPN22 at chr1p13.2, BCL2L11 at chr2q13, and CCR3 at chr3p21.31 (Psingle trait<1×10-3 and Pmeta<5×10-8), highlighting potential shared pathogenesis including accelerating atherosclerosis, upregulating oxidative stress, and vascular permeability. Finally, Mendelian randomization estimates showed limited evidence of causality between RA and CVD. Conclusions Our results supported shared genetic pathogenesis rather than causality in explaining the observed association between RA and CVD. The identified shared genetic factors provided insights into potential novel therapeutic target for RA-CVD comorbidities.

Disparities in Lupus and the Role of Social Determinants of Health: Current State of Knowledge and Directions for Future Research.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. The complex relationships between race and ethnicity and social determinants of health (SDOH) in influencing SLE and its course are increasingly appreciated. Multiple SDOH have been strongly associated with lupus incidence and outcomes and contribute to health disparities in lupus. Measures of socioeconomic status, including economic instability, poverty, unemployment, and food insecurity, as well as features of the neighborhood and built environment, including lack of safe and affordable housing, crime, stress, racial segregation, and discrimination, are associated with race and ethnicity in the US and are risk factors for poor outcomes in lupus. In this scientific statement, we aimed to summarize current evidence on the role of SDOH in relation to racial and ethnic disparities in SLE and SLE outcomes, primarily as experienced in the U.S. Lupus Foundation of America's Health Disparities Advisory Panel, comprising 10 health disparity experts, including academic researchers and patients, who met 12 times over the course of 18 months in assembling and reviewing the data for this study. Sources included articles published from 2011 to 2023 in PubMed, Centers for Disease Control and Prevention data, and bibliographies and recommendations. Search terms included lupus, race, ethnicity, and SDOH domains. Data were extracted and synthesized into this scientific statement. Poorer neighborhoods correlate with increased damage, reduced care, and stress-induced lupus flares. Large disparities in health care affordability, accessibility, and acceptability exist in the US, varying by region, insurance status, and racial and minority groups. Preliminary interventions targeted social support, depression, and shared-decision-making, but more research and intervention implementation and evaluation are needed. Disparities in lupus across racial and ethnic groups in the US are driven by SDOH, some of which are more easily remediable than others. A multidimensional and multidisciplinary approach involving various stakeholder groups is needed to address these complex challenges, address these diminish disparities, and improve outcomes.

Comparative Risks of Infection With Belimumab Versus Oral Immunosuppressants in Patients With Nonrenal Systemic Lupus Erythematosus.

OBJECTIVE: We investigated the comparative risk of infection with belimumab versus oral immunosuppressants for the treatment of systemic lupus erythematosus (SLE). METHODS: Using observational data from a US multicenter electronic health record database, we identified patients with SLE but without lupus nephritis who initiated belimumab, azathioprine, methotrexate, or mycophenolate between 2011 and 2021. We designed and emulated hypothetical target trials to estimate the cumulative incidence and hazard ratios (HRs) of serious infection and hospitalization for serious infection comparing belimumab versus each oral immunosuppressant. We used propensity score overlap weighting to balance baseline covariates and adjusted for adherence to treatment group using inverse probability of treatment weighting. We also assessed the control outcome of traumatic injury. RESULTS: Among 21,481 patients, we compared 2841 and 6343 initiators of belimumab and azathioprine, 2642 and 8242 initiators of belimumab and methotrexate, and 2813 and 8407 initiators of belimumab and mycophenolate, respectively. After propensity score overlap weighting, all covariates were balanced in each comparison. The mean age of the cohort was 45 years, and 94% were women. Compared with azathioprine and mycophenolate, belimumab was associated with lower risks of both serious infection (HR 0.82; 95% confidence interval [CI] 0.72-0.92 and HR 0.69; 95% CI 0.61-0.78) and hospitalization for infection (HR 0.73; 95% CI 0.57-0.94 and HR 0.56 95% CI 0.43-0.71). The risk of infection was also lower for belimumab compared with methotrexate (HR 0.86; 95% CI 0.76-0.97). There were no differences in traumatic injury risks across treatment groups. CONCLUSION: Belimumab was associated with lower risks of serious infection than with oral immunosuppressants. This finding should inform risk/benefit considerations for SLE treatment.

Machine learning identifies clusters of longitudinal autoantibody profiles predictive of systemic lupus erythematosus disease outcomes.

OBJECTIVES: A novel longitudinal clustering technique was applied to comprehensive autoantibody data from a large, well-characterised, multinational inception systemic lupus erythematosus (SLE) cohort to determine profiles predictive of clinical outcomes. METHODS: Demographic, clinical and serological data from 805 patients with SLE obtained within 15 months of diagnosis and at 3-year and 5-year follow-up were included. For each visit, sera were assessed for 29 antinuclear antibodies (ANA) immunofluorescence patterns and 20 autoantibodies. K-means clustering on principal component analysis-transformed longitudinal autoantibody profiles identified discrete phenotypic clusters. One-way analysis of variance compared cluster enrolment demographics and clinical outcomes at 10-year follow-up. Cox proportional hazards model estimated the HR for survival adjusting for age of disease onset. RESULTS: Cluster 1 (n=137, high frequency of anti-Smith, anti-U1RNP, AC-5 (large nuclear speckled pattern) and high ANA titres) had the highest cumulative disease activity and immunosuppressants/biologics use at year 10. Cluster 2 (n=376, low anti-double stranded DNA (dsDNA) and ANA titres) had the lowest disease activity, frequency of lupus nephritis and immunosuppressants/biologics use. Cluster 3 (n=80, highest frequency of all five antiphospholipid antibodies) had the highest frequency of seizures and hypocomplementaemia. Cluster 4 (n=212) also had high disease activity and was characterised by multiple autoantibody reactivity including to antihistone, anti-dsDNA, antiribosomal P, anti-Sjögren syndrome antigen A or Ro60, anti-Sjögren syndrome antigen B or La, anti-Ro52/Tripartite Motif Protein 21, antiproliferating cell nuclear antigen and anticentromere B). Clusters 1 (adjusted HR 2.60 (95% CI 1.12 to 6.05), p=0.03) and 3 (adjusted HR 2.87 (95% CI 1.22 to 6.74), p=0.02) had lower survival compared with cluster 2. CONCLUSION: Four discrete SLE patient longitudinal autoantibody clusters were predictive of long-term disease activity, organ involvement, treatment requirements and mortality risk.

Association of Reported Nonsteroidal Anti-Inflammatory Drug (NSAID) Adverse Drug Reactions With Opioid Prescribing After Total Joint Arthroplasty.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for postoperative pain management, but use may be precluded by the report of adverse drug reactions (ADRs). The effect of NSAID ADR labeling on opioid prescribing after total joint arthroplasty (TJA) is unknown. OBJECTIVE: To assess the association between NSAID ADRs and postoperative opioid prescribing after TJA, a common surgical procedure. METHODS: We performed a retrospective cohort study of adults who underwent total joint (knee or hip) replacement in a single hospital network between April, 1, 2016, and December 31, 2019. Demographic information, clinical and surgical characteristics, and prescription data were obtained from the electronic health record. We studied the association between reported NSAID ADRs and postoperative opioid prescribing in a propensity score-matched sample over 1 year of follow-up. RESULTS: NSAID ADRs were reported by 9.6% of the entire cohort (n = 584/6091). NSAID ADR was associated with 41% higher odds of receipt of opioid prescriptions at 181 to 365 days after hospital discharge (95% confidence interval: 13%-75%) in a propensity score-matched sample. Over 98% of individuals received an opioid prescription at the time of hospital discharge, with no difference in overall median opioid dose prescribed by NSAID ADR status. However, more patients with NSAID ADRs (7.6% vs 4.7%) received cumulative opioid doses ≥ 750 morphine milligram equivalents (MME) at discharge (P = .004). CONCLUSION: Reported NSAID ADR was associated with increased risk for prolonged receipt of opioids at 181 to 365 days postoperatively. Patients with NSAID ADRs more frequently received cumulative opioid doses ≥ 750 MME at discharge after TJA. Clarification and evaluation of reported NSAID ADRs may be particularly beneficial for surgical patients at high risk for prolonged receipt of opioids.

Over-the-counter fish oil supplementation and pro-resolving and pro-inflammatory lipid mediators in rheumatoid arthritis.

OBJECTIVE: Little is known about the effects of over-the-counter fish oil (FO) supplements on circulating omega-3 polyunsaturated fatty acid (n-3 PUFA)-derived specialized pro-resolving mediators (SPMs), nor about whether having a chronic inflammatory disease such as rheumatoid arthritis (RA) influences SPM levels. We investigated associations between over-the-counter n-3 PUFA FO supplementation and circulating SPMs among patients with vs. without RA. METHODS: We studied 104 participants: 26 with RA taking FO matched by age and sex to 26 with RA not taking FO, 26 without RA taking FO, and 26 without RA not taking FO. Targeted-liquid chromatography-tandem mass spectroscopy was performed on patient plasma to identify and quantify 27 lipid mediators (including eicosanoids and SPMs). We performed t-tests and then multivariable linear regression analyses to assess whether having RA or taking FO supplements was associated with circulating lipid mediator concentrations, adjusting for age, race, sex, smoking, body mass index, and current medication use (statins, prednisone and immunomodulators among RA cases only). We tested for interactions between FO supplementation and RA status. We also conducted Spearman's correlations between EPA, DHA, and ARA and their downstream metabolites. RESULTS: Among patients who were taking FO compared to those who were not, in multivariable- adjusted analyses, SPM substrates EPA and DHA were both elevated as were several of their pro-resolving bioactive products, including 15- and 18-HEPE from EPA, and 14- and 17-HDHA from DHA, which are substrates for specific SPMs. While E-series and D-series resolvins were present and identified, we did not find statistical elevations of other SPMs. Results were similar among patients with RA and patients without RA, taking vs. not taking FO supplementation (no formal statistical interaction observed). There was a strong positive correlation between EPA and DHA and their immediate downstream SPM precursors (18-HEPE and15-HEPE from EPA; 17-HDHA and 14-HDHA from DHA) among all patients. CONCLUSION: Patients taking FO supplements, regardless of RA status, not only had higher blood levels of EPA and DHA, but also of their enzymatic products 18-HEPE (E-series resolvin precursors), 15-HEPE and 17-HDHA (D-series resolvin and protectin precursors). Patients with RA, an inflammatory autoimmune disease, may be able to augment some SPM precursor reserves, similarly to matched controls without RA, by taking oral FO supplements.

Association of Healthy Lifestyle Behaviors and the Risk of Developing Rheumatoid Arthritis Among Women.

OBJECTIVE: To investigate whether a healthy lifestyle, defined by a healthy lifestyle index score (HLIS), was associated with rheumatoid arthritis (RA) risk, overall and with seropositive/seronegative subtypes. METHODS: We analyzed female nurses in the Nurses' Health Study (NHS, 1986-2016) and NHSII (1991-2017). Lifestyle and medical information were collected on biennial questionnaires. Medical records confirmed incident RA and serostatus. The HLIS index includes 5 modifiable components: smoking, alcohol consumption, body mass index, physical activity, and diet. Cox regression, adjusted for confounders, modeled associations between HLIS and incident RA. The population attributable risk estimated the proportion of incident RA preventable if participants adopted ≥4 healthy lifestyle factors. RESULTS: A total of 1,219 incident RA cases (776 seropositive, 443 seronegative) developed in 4,467,751 person-years. Higher (healthier) HLIS was associated with lower overall RA risk (hazard ratio [HR] 0.86 [95% confidence interval (95% CI) 0.82-0.90]), seropositive RA risk (HR 0.85 [95% CI 0.80-0.91]), and seronegative RA risk (HR 0.87 [95% 0.80-0.94]). Women with 5 healthy lifestyle factors had the lowest risk (HR 0.42 [95% CI 0.22-0.80]). The population attributable risk for adhering to ≥4 lifestyle factors was 34% for RA. CONCLUSION: In this prospective cohort, healthier lifestyle was associated with a lower RA risk. A substantial proportion of RA may be preventable by a healthy lifestyle.

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.

Association of Ultraviolet B Radiation and Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Studies.

OBJECTIVE: Ultraviolet (UV) radiation exposure is associated with photosensitivity, rashes, and flares in systemic lupus erythematosus (SLE). However, it is not known whether UV exposure increases risk of developing SLE. We examined UV exposure and SLE risk in a large prospective cohort. METHODS: The Nurses' Health Study (NHS) enrolled 121,700 US female nurses in 1976; in 1989, 116,429 nurses were enrolled in NHS II. Biennial questionnaires collected lifestyle and medical data. Self-reported incident SLE by American College of Rheumatology classification criteria was confirmed by medical record review. Ambient UV exposure was estimated by linking geocoded residential addresses with a spatiotemporal UV exposure model. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) across tertiles of time-varying cumulative average UV. We examined SLE risk overall and stratified by anti-Ro/La antibodies and by cutaneous manifestations from 1976 through 2014 (NHS)/2015 (NHS II), adjusting for confounders. RESULTS: With 6,054,665 person-years of exposure, we identified 297 incident SLE cases; the mean ± SD age at diagnosis was 49.8 ± 10.6 years. At diagnosis, 16.8% of women had +anti-Ro/La, and 80% had either +anti-Ro/La or ≥1 cutaneous manifestation. Compared with the lowest UV exposure tertile, risk of overall SLE was increased, but not significantly (HR 1.28 [95%CI 0.96-1.70]). Women in the highest tertile had increased risk of malar rash (HR 1.62 [95% CI 1.04-2.52]). CONCLUSION: Cumulative UV exposure was not associated with SLE risk. Higher UV exposure, however, was associated with increased risk of malar rash at presentation. UV exposure may trigger SLE onset with malar rash among susceptible women.