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Objective: To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population-based cohort.Design: Retrospective cohort study.Setting: California, USA.Population: All live singleton births in California between 2007 and 2011 were analysed. Patients with autoimmune disease at delivery were identified by International Classification of Diseases, Ninth Revision , Clinical Modification (ICD-9-CM), codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA).Methods: Maternally linked hospital and birth certificate records of 2 481 516 deliveries were assessed (SLE n = 2272, RA n = 1501, SSc n = 88, JIA n = 187, DM/PM n = 38). Multivariable Poisson regression models estimated the risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared with the general obstetric population, adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care.Main Outcome Measures: Preterm birth (PTB) was assessed overall (20-36 weeks of gestation) and by subphenotype: preterm prelabour rupture of membranes (PPROM), spontaneous birth, or medically indicated PTB. The risk of PTB overall and for each phenotype was partitioned by gestational age: early (20-31 weeks of gestation) and late (32-36 weeks of gestation).Results: Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27, 95% CI 3.01-3.56), RA (RR 2.04, 95% CI 1.79-2.33), SSc (RR 3.74, 95% CI 2.51-5.58), JIA (RR 2.23, 95% CI 1.54-3.23), and DM/PM (RR 5.26, 95% CI 3.12-8.89). These elevated risks were observed for the majority of PTB phenotypes as well.Conclusions: Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counselling and close monitoring during pregnancy is crucial.Tweetable Abstract: This study found that women with systemic autoimmune diseases have an elevated risk of preterm birth phenotypes. [ABSTRACT FROM AUTHOR]

Background: Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine.Methods: To evaluate variation in mortality following the withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale).Results: We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval [CI] 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (χ(2) test for overall difference, p < 0.001). Most deaths (70.2% [160/228], 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ(2) test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care.Interpretation: We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury. [ABSTRACT FROM AUTHOR]

Objective: To measure small-area variations in sales per capita of tumour necrosis factor (TNF) inhibitors. Methods: For 2000-2009, sales data on etanercept, infliximab, and adalimumab were retrieved from the Swedish National Corporation of Pharmacies, which keeps data on drugs dispensed in ambulatory care and hospitals. As points of reference, data were retrieved on all drugs, non-biologic treatments for chronic inflammatory disorders (sulfasalazine, methotrexate, azathioprine), and for a biologic used in a different therapeutic area (trastuzumab). As a corollary measure to sales per capita, penetration of biologics in the rheumatoid arthritis (RA) population was calculated using nationwide registers. Small areas were defined as the 21 counties of Sweden. Results: From 2000 to 2009, annual TNF inhibitor sales increased 9-fold from 195 to 1779 million SEK (0.7-5.0% of total drug expenditure). The county variation in sales per capita, initially 6.2-fold (coefficient of variation 42%), decreased to 2.3-fold in 2009 (24%). During the same period, total drug expenditure per capita remained at a 1.2-fold county variation (4-6%). Sales per capita variations of non-biologic treatments against chronic inflammatory diseases ranged from 1.5 to 1.8 (12-16%). For trastuzumab, a 3.2-fold variation (30%) was observed in 2009. At the patient level, there was a 2-fold county variation (from 10% to 21%) in biologic penetration in RA. County-specific sales per capita were associated with mean RA duration (r = −0.52, p = 0.015) and C-reactive protein at treatment initiation (r = −0.49, p = 0.025), while pain was borderline significant (r = −0.43, p = 0.055). Conclusions: Despite universal access to treatment, substantial but decreasing small-area variations were observed. Although geographic variations are anticipated initially, their persistence calls for investigation of patient equity and treatment appropriateness as counties seem to have different initiation thresholds. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To compare the effectiveness of 3 therapeutic strategies in preventing progressive joint damage, in a population-based cohort. The 3 strategies were infliximab with concomitant disease-modifying antirheumatic drugs (DMARDs), etanercept with concomitant DMARDs, and etanercept alone. METHODS: We used sequential radiographs to assess all patients who were treated with infliximab or etanercept for >10 months. The rates of erosion progression and joint space narrowing (JSN) were analyzed using multivariate regression models for longitudinal data, with adjustment for potential confounders. RESULTS: A total of 372 patients treated with anti-tumor necrosis factor (TNF) therapies met the inclusion criteria. The baseline characteristics of the patients assigned to the 3 strategies were not significantly different, except that, as expected, more patients were receiving combination therapy with infliximab. The combination of infliximab plus DMARDs was significantly more effective than etanercept alone for controlling erosion progression (P < 0.001), but the effectiveness of the 2 combination-treatment strategies was similar (P = 0.07). The combination of infliximab plus DMARDs was also more effective at controlling progressive JSN compared with etanercept alone (P = 0.04) or etanercept plus DMARDs (P = 0.02). Treatment with anti-TNF agents (infliximab or etanercept) plus concomitant DMARDs was more effective than treatment with etanercept alone for controlling erosion progression (P = 0.045). CONCLUSION: When combined with traditional DMARDs, both etanercept and infliximab appear to offer similar protection against progressive structural joint damage, and combination therapy with either of these agents appears to be more effective than treatment with etanercept alone. [ABSTRACT FROM AUTHOR]

Objectives: To describe the uptake of anti-SARS-CoV2 vaccination in 2021 and investigate vaccine effectiveness in systemic lupus erythematosus (SLE) patients in Sweden., Methods: The cumulative incidence of first anti-SARS-CoV2 vaccination was estimated among SLE patients from the Swedish National Patient Register and matched comparators living in Sweden on January 1, 2021. To assess vaccine effectiveness, we included the individuals who received two doses of anti-SARS-CoV2 mRNA vaccines before year 2022, with no COVID-19 diagnosis code before the 2nd vaccine dose. Hospitalization rates with COVID-19 as main diagnosis during the year after second dose were compared between SLE patients and comparators in multivariable-adjusted marginal Cox models, overall and stratified by immunosuppressive treatment received during the year before second vaccine dose., Results: Vaccination uptake was similar between SLE patients and comparators. By December 2021, 9% of both SLE and comparators had not received any vaccine doses. Among 5585 SLE patients and 37,102 comparators, 11 COVID-19 hospitalizations in the SLE group and 20 in the comparators occurred. SLE was associated with a higher risk of COVID-19 hospitalization (HR = 3.47, 95%CI 1.63-7.39). The HR was higher for immunosuppressive-treated SLE (7.03 95%CI 3.00-16.46) than for immunosuppressive-untreated (1.50 95%CI 0.34-6.60). Vaccination of immunosuppressive-untreated SLE patients had similar effectiveness as comparators., Conclusion: Anti-SARS-CoV2 vaccination coverage was similar between SLE patients and the general population in Sweden. Even though the incidence of post-vaccination COVID-19 hospitalization was very low, vaccine effectiveness was diminished in SLE patients compared to the general population and lowest in those treated with immunosuppressants., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In population-based research, pregnancy may be a repeated event. Despite published guidance on how to address repeated pregnancies to the same individual, a variety of approaches are observed in perinatal epidemiological studies. While some of these approaches are supported by the chosen research question, others are consequences of constraints inherent to a given dataset (eg, missing parity information). These decisions determine how appropriately a given research question can be answered and overall generalizability., Objective: To compare common cohort selection and analytic approaches used for perinatal epidemiological research by assessing the prevalence of two perinatal outcomes and their association with a clinical and a social independent variable., Study Design: Using vital records linked to maternal hospital discharge records for singleton births, we created four cohorts: (1) all-births (2) randomly selected one birth per individual (3) first-observed birth per individual (4) primiparous-births (parity 1). Sampling of births was not conditional on cluster (ie, we did not sample all births by a given mother, but rather sampled individual births). Study outcomes were severe maternal morbidity (SMM) and preeclampsia/eclampsia, and the independent variables were self-reported race/ethnicity (as a social factor) and systemic lupus erythematosus. Comparing the four cohorts, we assessed the distribution of maternal characteristics, the prevalence of outcomes, overall and stratified by parity, and risk ratios (RR) for the associations of outcomes with independent variables. Among all-births, we then compared RR from three analytic strategies: with standard inference that assumes independently sampled births to the same mother in the model, with cluster-robust inference, and adjusting for parity., Results: We observed minor differences in the population characteristics between the all-birth (N=2736,693), random-selection, and first-observed birth cohorts (both N=2284,660), with more substantial differences between these cohorts and the primiparous-births cohort (N=1054,684). Outcome prevalence was consistently lowest among all-births and highest among primiparous-births (eg, SMM 18.9 per 1000 births among primiparous-births vs 16.6 per 1000 births among all-births). When stratified by parity, outcome prevalence was always the lowest in births of parity 2 and highest among births of parity 1 for both outcomes. RR differed for study outcomes across all four cohorts, with the most pronounced differences between the primiparous-birth cohort and other cohorts. Among all-births, robust inference minimally impacted the confidence bounds of estimates, compared to the standard inference, that is, crude estimates (eg, lupus-SMM association: 4.01, 95% confidence intervals [CI] 3.54-4.55 vs 4.01, 95% CI 3.53-4.56 for crude estimate), while adjusting for parity slightly shifted estimates, toward the null for SMM and away from the null for preeclampsia/eclampsia., Conclusion: Researchers should consider the alignment between the methods they use, their sampling strategy, and their research question. This could include refining the research question to better match inference possible for available data, considering alternative data sources, and appropriately noting data limitations and resulting bias, as well as the generalizability of findings. If parity is an established effect modifier, stratified results should be presented., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: In 2019, the EULAR/American College of Rheumatology developed classification criteria for systemic lupus erythematosus (SLE). A positive correlation between summary score at diagnosis and SLE disease activity at five years has been noted in adult patients with lupus, but little is known among the pediatric population. We evaluated the prognostic value of higher summary scores and number of extrarenal domains at diagnosis (low/moderate number [1-5] vs high number [6-9]) to renal outcomes after one year of treatment in pediatric patients with lupus nephritis (LN)., Methods: This retrospective, single-center cohort study included 74 pediatric patients with LN. Published pediatric renal response definitions were used for our outcome measure (no, partial, and complete response). Descriptive statistics were reported, and an ordinal logistic regression estimated adjusted odds ratios (ORs) for renal response including 95% confidence intervals (CIs)., Results: Patients with high extrarenal domains had OR 1.47 (95% CI 0.55-2.91) of having a complete renal response compared to patients with low/moderate domains. Patients with a summary score <30 had OR 1.31 (95% CI 0.50-3.44) of having a complete renal response relative to a summary score ≥30, though a larger proportion of patients with a summary score of ≥30 had no renal response after one year of treatment., Conclusion: More extrarenal domains at diagnosis did not have a statistically significant impact on renal response at one year, nor did a higher summary score. However, a larger portion of patients with a summary score <30 achieved complete renal response compared to patients with a score ≥30., (© 2024 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: It is known that cesarean birth affects maternal outcomes in subsequent pregnancies, but specific effect estimates are lacking. We sought to quantify the effect of cesarean birth reduction among nulliparous, term, singleton, vertex (NTSV) births (i.e., preventable cesarean births) on severe maternal morbidity (SMM) in the second birth., Methods: We examined birth certificates linked with maternal hospitalization data (2007-19) from California for NTSV births with a second birth (N = 779,382). The exposure was cesarean delivery in first birth and the outcome was SMM in the second birth. We used adjusted Poisson regression models to calculate risk ratios and population attributable fraction for SMM in the second birth and conducted a counterfactual impact analysis to estimate how lowering NTSV cesarean births could reduce SMM in second birth., Results: The adjusted risk ratio for SMM in the second birth given a prior cesarean birth was 1.7 (95% CI 1.5-1.9); 15.5% (95% CI 15.3%-15.7%) of this SMM may be attributable to prior cesarean birth. In a counterfactual analysis where 12% of the California population least likely to get a cesarean birth instead delivered vaginally, we observed 174 fewer SMM events in a population of individuals with a low-risk first birth and a subsequent birth., Conclusions: In our counterfactual analysis, lowering primary cesarean birth among a NTSV population was associated with fewer downstream SMM events in subsequent births and overall. Additionally, our findings reflect the importance of considering the cumulative accrual of risks across the reproductive life-course., Competing Interests: Conflicts of Interest: None declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Diagnostic errors in outpatient settings lead to significant consequences, especially in rare diseases such as systemic lupus erythematosus (SLE). A recent vignette-based experimental study revealed that demographic factors influenced rheumatologists' diagnoses of SLE, raising concerns about potential diagnostic biases. We conducted a qualitative study to contextualize these results to generate insights about diagnostic challenges and biases, and root causes., Methods: We conducted 41 semistructured interviews among US rheumatologists. Transcripts were independently coded by at least two coders using a hybrid deductive-inductive approach and thematic analysis. A team of four researchers reviewed and defined themes collectively, and also resolved any discrepancies., Results: Participants were 66% women, and 49% had more than10 years of postfellowship experience. Five major themes were generated, including receiving training through the lens of race or sex, the role of the documented epidemiology of SLE, pattern recognition and test-taking strategies, patient vignettes as an imperfect proxy for patient interactions, and varied consequences to patients from diagnostic bias. Participants noted that the consequences of diagnostic bias could include progressed disease from delayed diagnosis, unnecessary and inappropriate treatment due to missed diagnosis or misdiagnosis, and increased cost and harm., Conclusion: This study underscores the unique challenges of diagnosing SLE, with complex factors contributing to diagnosis bias and delays. Interventions during medical education could prevent downstream diagnostic biases. Future research should explore interventions to mitigate diagnostic bias and refine vignettes to better mirror real-world clinical scenarios. Understanding diagnostic bias in SLE is crucial for improving patient outcomes and refining medical training practices., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: The goal of this study was to investigate the risk of preterm birth subtypes and hypertensive disorders of pregnancy in patients with systemic vasculitis using large, statewide databases., Methods: Births to nulliparous patients with prevalent systemic vasculitides (Takayasu arteritis [TAK], Behçet disease [BD], antineutrophil cytoplasmic antibody-associated vasculitis [AAV], and Kawasaki disease [KD]) were identified using International Classification of Diseases, Ninth Revision codes in linked administrative data and birth records from the California Department of Health Care Access and Information and California Vital Statistics from 1991 to 2012. Hypertensive disorders of pregnancy and preterm delivery (PTD) subtypes were identified. Multivariable-adjusted Poisson models estimated risk ratios (RRs) of these outcomes compared with the general birthing population without history of rheumatic disease., Results: A total of 96 births to nulliparous patients with systemic vasculitis were identified (TAK, 14; AAV, 31; BD, 26; KD, 15) and compared with 4,191,900 births of the nulliparous general population. Adjusted RRs for all PTD types were elevated in patients with vasculitis (RR 3.21, 95% confidence interval [CI] 2.15-4.79), as were the RRs of all PTD subtypes including preterm premature rupture of membranes (RR 4.30, 95% CI 2.05-9.01) and spontaneous PTD (RR 4.99, 95% CI 3.01-8.28). Of the spontaneous PTDs among patients with vasculitis, 16.7% were early PTDs (20-31 weeks), with the remaining 83.3% occurring between 32 to 36 weeks. Patients with vasculitis also had an elevated risk of hypertensive disorders of pregnancy (RR 2.96, 95% CI 1.72-5.10)., Conclusion: Among first-time births, we found that patients with systemic vasculitis have an elevated risk of PTD subtypes as well as hypertensive disorders of pregnancy., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Medical diagnosis in practice connects to research through continuous feedback loops: Studies of diagnosed cases shape our understanding of disease, which shapes future diagnostic practice. Without accounting for an imperfect and complex diagnostic process in which some cases are more likely to be diagnosed correctly (or diagnosed at all), the feedback loop can inadvertently exacerbate future diagnostic errors and biases., Framework: A feedback loop failure occurs if misleading evidence about disease etiology encourages systematic errors that self-perpetuate, compromising future diagnoses and patient care. This article defines scenarios for feedback loop failure in medical diagnosis., Design: Through simulated cases, we characterize how disease incidence, presentation, and risk factors can be misunderstood when observational data are summarized naive to biases arising from diagnostic error. A fourth simulation extends to a progressive disease., Results: When severe cases of a disease are diagnosed more readily, less severe cases go undiagnosed, increasingly leading to underestimation of the prevalence and heterogeneity of the disease presentation. Observed differences in incidence and symptoms between demographic groups may be driven by differences in risk, presentation, the diagnostic process itself, or a combination of these. We suggested how perceptions about risk factors and representativeness may drive the likelihood of diagnosis. Differing diagnosis rates between patient groups can feed back to increasingly greater diagnostic errors and disparities in the timing of diagnosis and treatment., Conclusions: A feedback loop between past data and future medical practice may seem obviously beneficial. However, under plausible scenarios, poorly implemented feedback loops can degrade care. Direct summaries from observational data based on diagnosed individuals may be misleading, especially concerning those symptoms and risk factors that influence the diagnostic process itself., Highlights: Current evidence about a disease can (and should) influence the diagnostic process. A feedback loop failure may occur if biased "evidence" encourages diagnostic errors, leading to future errors in the evidence base.When diagnostic accuracy varies for mild versus severe cases or between demographic groups, incorrect conclusions about disease prevalence and presentation will result without specifically accounting for such variability.Use of demographic characteristics in the diagnostic process should be done with careful justification, in particular avoiding potential cognitive biases and overcorrection., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: RCA is a full-time employee of Mathematica Inc. JHC is co-founder of Reaction Explorer LLC, which develops and licenses organic chemistry education software. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Foundation for the National Institutes of Health (R01 AI154533, LM013365, T32 LM012409), Stanford University, School of Medicine, Stanford University, WHSDM Seed Grant, AIMI-HCAI Partnership grant, SAGE center funds, Stanford Clinical Excellence Research Center funds, Stanford Graduate Fellowship.

Objective: Patients with systemic lupus erythematosus (SLE) are at risk for pregnancy complications such as pre-eclampsia and eclampsia. These clinically important complications are associated with maternal morbidity, mortality, and postpartum cardiovascular disease. Some studies suggest that hydroxychloroquine (HCQ) may reduce pre-eclampsia risk in lupus pregnancy. Using a cohort of pregnant patients with prevalent SLE at Kaiser Permanente Northern California (KPNC), we investigated whether HCQ treatment in early pregnancy reduced the risk of pre-eclampsia or eclampsia., Methods: Among pregnant patients with SLE from 2011 to 2020, we assessed HCQ treatment from three months before pregnancy through the first trimester. HCQ exposure was defined multiple ways to account for adherence and duration of treatment. Propensity scores accounted for multiple confounders and modified Poisson models estimated risk ratios (RRs) and 95% confidence intervals of the association between HCQ treatment and pre-eclampsia or eclampsia. Effect modification by pregestational hypertension, history of nephritis, and antiphospholipid antibody (aPL) status was investigated through stratified analysis., Results: There were 399 pregnancies among 324 patients with SLE at KPNC between 2011 and 2020. Considering multiple exposure definitions, we consistently found a null association between HCQ and pre-eclampsia or eclampsia. The RRs were consistently lower among nullipara patients, and RRs were consistently protective but not statistically significant among the high-risk subgroup of patients with a history of nephritis, aPL positivity, or pregestational hypertension (for both nullipara and multipara patients)., Conclusion: Although this study found no reduced risk of HCQ on pre-eclampsia or eclampsia, residual confounding may be attenuating the effect despite an integrated health care delivery system setting with detailed clinical data., (© 2024 The Author(s). Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Introduction: Patients with systemic lupus erythematosus (SLE) bear a significant burden of pain. We aimed to identify factors that distinguish patients with SLE referred to comprehensive pain clinics and those who are not. Characterizing this patient population will identify unmet needs in SLE management and inform efforts to improve pain care in rheumatology., Methods: Among patients with SLE with ≥2 rheumatology clinic visits in a large hospital system from 1998 to 2023 (n = 1319), we examined factors that distinguished those who had at least one visit to multidisciplinary pain clinics (n = 77, 5.8%) from those who did not have any visits (n = 1242, 94.2%) with a focus on biopsychosocial and socioeconomic characteristics. We extracted demographic data and ICD-9/ICD-10 codes from the EHR., Results: Patients with SLE attending the pain clinics exhibited characteristics including average older age (mean age ± SD: 54.1 ± 17.9 vs. 48.4 ± 19.9), a higher likelihood of relying on public health insurance (50.7% vs. 34.2%), and a greater representation of Black patients (9.1% vs. 4.4%) compared to SLE patients not seen in pain clinics. Nearly all patients seen at the pain clinics presented with at least one chronic overlapping pain condition (96.1% vs. 58.6%), demonstrated a higher likelihood of having a mental health diagnosis (76.7% vs. 42.4%), and exhibited a greater number of comorbidities (mean ± SD: 6.0 ± 3.0 vs. 2.9 ± 2.6) compared to those not attending the pain clinic., Conclusion: We found notable sociodemographic and clinical differences between these patient populations. Patients presenting with multiple comorbidities might benefit from further pain screening and referral to pain clinics to provide comprehensive care, and earlier referral could mitigate the development and progression of multimorbidities., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Systemic lupus erythematosus (SLE) disproportionately affects women during childbearing years, and hydroxychloroquine (HCQ) is the standard first-line treatment. Preeclampsia complicates up to one-third of pregnancies in lupus patients, although reports vary by parity and multifetal gestation. We investigated whether taking HCQ early in pregnancy may reduce the risk of preeclampsia., Methods: We studied 1,068 live birth singleton pregnancies among 1,020 privately insured patients with SLE (2007-2016). HCQ treatment was defined as three months preconception through the first trimester, and prescription fills were a proxy for taking HCQ. Modified Poisson regression estimated risk ratios (RRs) and 95% confidence intervals (CIs), stratified by parity. Propensity scores accounted for confounders, and stratified analyses examined effect modification., Results: Approximately 15% of pregnant patients were diagnosed with preeclampsia. In 52% of pregnancies, patients had one or more HCQ fills. Pregnant patients exposed to HCQ had more comorbidities, SLE activity, and azathioprine treatment. We found no evidence of a statistical association between HCQ and preeclampsia among nulliparous (RR 1.26 [95% CI 0.82-1.93]) and multiparous pregnancies (RR 1.20 [95% CI 0.80-1.70]). Additional controls for confounding decreased the RRs toward the null (nulliparous pregnancy, propensity score-adjusted [PS-adj] RR 1.09 [95% CI 0.68-1.76]; multiparous pregnancy, PS-adj RR 1.01 [95% CI 0.66-1.53])., Conclusion: Using a large insurance-based database, we did not observe a decreased risk of preeclampsia associated with HCQ treatment in pregnancy, although we cannot rule out residual and unmeasured confounding and misclassification. Further studies leveraging large population-based data and prospective collection could characterize how HCQ influences preeclampsia risk in pregnant patients with SLE and among persons at greater risk of hypertensive disorders of pregnancy., (© 2024 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Web-based surveys can be effective data collection instruments; however, participation is notoriously low, particularly among professionals such as physicians. Few studies have explored the impact of varying amounts of monetary incentives on survey completion., Objective: This study aims to conduct a randomized study to assess how different incentive amounts influenced survey participation among neurologists in the United States., Methods: We distributed a web-based survey using standardized email text to 21,753 individuals randomly divided into 5 equal groups (≈4351 per group). In phase 1, each group was assigned to receive either nothing or a gift card for US $10, $20, $50, or $75, which was noted in the email subject and text. After 4 reminders, phase 2 began and each remaining individual was offered a US $75 gift card to complete the survey. We calculated and compared the proportions who completed the survey by phase 1 arm, both before and after the incentive change, using a chi-square test. As a secondary outcome, we also looked at survey participation as opposed to completion., Results: For the 20,820 emails delivered, 879 (4.2%) recipients completed the survey; of the 879 recipients, 622 (70.8%) were neurologists. Among the neurologists, most were male (412/622, 66.2%), White (430/622, 69.1%), non-Hispanic (592/622, 95.2%), graduates of American medical schools (465/622, 74.8%), and board certified (598/622, 96.1%). A total of 39.7% (247/622) completed their neurology residency more than 20 years ago, and 62.4% (388/622) practiced in an urban setting. For phase 1, the proportions of respondents completing the survey increased as the incentive amount increased (46/4185, 1.1%; 76/4165, 1.8%; 86/4160, 2.1%; 104/4162, 2.5%; and 119/4148, 2.9%, for US $0, $10, $20, $50, and $75, respectively; P<.001). In phase 2, the survey completion rate for the former US $0 arm increased to 3% (116/3928). Those originally offered US $10, $20, $50, and $75 who had not yet participated were less likely to participate compared with the former US $0 arm (116/3928, 3%; 90/3936, 2.3%; 80/3902, 2.1%; 88/3845, 2.3%; and 74/3878, 1.9%, for US $0, $10, $20, $50, and $75, respectively; P=.03). For our secondary outcome of survey participation, a trend similar to that of survey completion was observed in phase 1 (55/4185, 1.3%; 85/4165, 2%; 96/4160, 2.3%; 118/4162, 2.8%; and 135/4148, 3.3%, for US $0, $10, $20, $50, and $75, respectively; P<.001) and phase 2 (116/3928, 3%; 90/3936, 2.3%; 80/3902, 2.1%; 88/3845, 2.3%; and 86/3845, 2.2%, for US $0, $10, $20, $50, and $75, respectively; P=.10)., Conclusions: As expected, monetary incentives can boost physician survey participation and completion, with a positive correlation between the amount offered and participation., (©Saadiya Hawa, Shalmali Bane, Kayla Kinsler, Amadeia Rector, Yashaar Chaichian, Titilola Falasinnu, Julia F Simard. Originally published in JMIR Formative Research (https://formative.jmir.org), 14.05.2024.)

Objective: Although the population of patients with systemic lupus erythematosus (SLE) is racially and ethnically diverse, many study populations are homogeneous. Further, data are often lacking on critical factors, such as antiphospholipid antibodies (aPLs). We investigated live birth rates in patients with SLE at Kaiser Permanente Northern California, including race and ethnicity and aPL data., Methods: Electronic health records of pregnancies with outcomes observed from 2011 to 2020 were identified among patients with SLE. Prevalent SLE was defined as two or more International Classification of Diseases-coded visits seven or more days apart before the last menstrual period. We summarized patient characteristics, medication orders, health care use, and medication use. Pregnancy outcomes (live birth, stillbirth, spontaneous abortion, ectopic pregnancy, and molar pregnancy) were presented overall and stratified by race and ethnicity, aPL status, and nephritis history., Results: We identified 657 pregnancies among 453 patients with SLE. The cohort was diverse, reflecting the Northern California population (27% Asian, 26% Hispanic, 26% Non-Hispanic White, 13% Non-Hispanic Black, 5% multiracial, and approximately 2% Pacific Islander and Native American). Approximately 74% of observed pregnancies ended in live birth, 23% resulted in spontaneous abortion, 2% were ectopic or molar pregnancies, and <1% were stillbirths. There was limited variability in live births by race and ethnic group (72%-79%), aPL status (69.5%-77%), and nephritis history (71%-75%)., Conclusion: Our findings are consistent with previous studies; however, some methodologic differences may yield a range of live birth rates. We found that approximately 74% of pregnancies in patients with SLE ended in live birth, with modest variability in spontaneous abortion by race and ethnicity, nephritis history, and aPL status., (© 2024 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: To assess the infant risk of major congenital malformations (MCM) associated with first-trimester exposure to hydroxychloroquine (HCQ) among mothers with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA)., Methods: This population-based cohort study utilised Swedish nationwide registers and included all singleton births (2006-2021) among individuals with prevalent SLE or RA in Sweden. The exposure was filling ≥1 HCQ prescription during the first trimester. The outcome was infant MCM within one year of birth. Inverse probability of treatment weighting was applied to adjust for potential confounders (e.g. maternal smoking, body mass index, pregestational diabetes, and corticosteroids). Modified Poisson regression models with robust variance estimated risk ratios and 95% confidence intervals (RR 95%CI)., Results: We included 1,007 births (453 exposed) and 2,500 births (144 exposed) in the SLE and RA cohorts, respectively. The MCM risks in the SLE overall cohort, exposed, and unexposed groups were 3.6%, 3.7%, and 3.4%, respectively. The corresponding figures in the RA cohort were 4.4%, 5.6%, and 4.3%, respectively. The adjusted RRs (95%CI) were 1.29 (0.65-2.56) in the SLE cohort, 1.32 (0.56-3.13) in the RA cohort, and 1.30 (0.76-2.23) in the pooled analysis. The adjusted risk difference (exposed vs unexposed) was small (0.9% in SLE and 1.3% in RA). Sensitivity analyses examining different exposure and outcome windows yielded similar findings., Conclusions: First-trimester exposure to HCQ was not associated with a significantly increased risk of MCM. HCQ's benefits may outweigh the risks in managing SLE or RA during pregnancy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: The aim of this study was to investigate and compare different case definitions for chronic pain to provide estimates of possible misclassification when researchers are limited by available electronic health record and administrative claims data, allowing for greater precision in case definitions., Methods: We compared the prevalence of different case definitions for chronic pain (N = 3042) in patients with autoimmune rheumatic diseases. We estimated the prevalence of chronic pain based on 15 unique combinations of pain scores, diagnostic codes, analgesic medications, and pain interventions., Results: Chronic pain prevalence was lowest in unimodal pain phenotyping algorithms: 15% using analgesic medications, 18% using pain scores, 21% using pain diagnostic codes, and 22% using pain interventions. In comparison, the prevalence using a well-validated phenotyping algorithm was 37%. The prevalence of chronic pain also increased with the increasing number (bimodal to quadrimodal) of phenotyping algorithms that comprised the multimodal phenotyping algorithms. The highest estimated chronic pain prevalence (47%) was the multimodal phenotyping algorithm that combined pain scores, diagnostic codes, analgesic medications, and pain interventions. However, this quadrimodal phenotyping algorithm yielded a 10% overestimation of chronic pain compared to the well-validated algorithm., Conclusion: This is the first empirical study to our knowledge that shows that established common modes of phenotyping chronic pain can lead to substantially varying estimates of the number of patients with chronic pain. These findings can be a reference for biases in case definitions for chronic pain and could be used to estimate the extent of possible misclassifications or corrections in using datasets that cannot include specific data elements., (Copyright © 2024 by the Journal of Rheumatology.)

Objectives: We sought to examine temporal trends in adverse pregnancy outcomes among SSc pregnancies in a large nationwide sample., Methods: We used the National Inpatient Sample (NIS) database from 2000 - 2017 to derive national estimates of delivery-associated hospitalizations in the United States among patients with SSc. Each SSc delivery was matched to 100 non-SSc deliveries by age, delivery year, and race. We evaluated adverse pregnancy outcomes (APOs) including maternal and fetal death, cesarean delivery, hospital length of stay, preterm delivery, intrauterine growth restriction, and hypertensive disorders of pregnancy. We used multivariable regression models with an interaction term between SSc and year and adjusting for race, advanced maternal age, diabetes mellitus, and pre-existing hypertension to evaluate temporal trends in APOs among SSc and non-SSc deliveries., Results: From 2000 to 2017, there were 3740 delivery-associated hospitalizations for women with SSc. SSc was associated with an increased risk of all APOs compared to non-SSc deliveries. Fetal death declined in SSc deliveries from 49.0 per 1000 delivery-related admissions in 2000 - 2005 to 16.2 per 1000 in 2012 - 2017. There was a significant difference in trends for fetal death between SSc and non-SSc deliveries (p = 0.043), but the trends for other APOs did not differ between the two groups., Conclusions: In this large nationwide sample, the risk of fetal death among women with SSc markedly improved over the past 18 years. The risk for other APOs remained high in SSc deliveries compared to non-SSc deliveries, and further studies are needed to determine what strategies can improve these outcomes., Competing Interests: Declaration of Competing Interest LC reports grant funding from Boerhinger Ingelheim. She has served as a consultant for Eicos Sciences, Mitsubishi Tanabe, Genentech, Gilead, Kyverna, and Jasper. All other authors report no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The risk of end-stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of SLE patients., Methods: By means of the Danish National Patient Registry, we identified 3,178 adult patients diagnosed as having SLE between January 1, 1996, and July 31, 2018. DM was defined as the date of first hospital contact for DM or date of a first prescription of an antidiabetic drug. ESRD was defined as first registration of dialysis, renal transplant, or terminal renal insufficiency in the Danish National Patient Registry. ESRD incidence was compared between SLE patients with DM (SLE-DM) and those without DM (SLE-non-DM). Hazard ratios (HRs), adjusted for sex, age, educational level, and occupational status at baseline were calculated for sex, age, educational level, and hypertension (at baseline or during follow-up) strata. The overall hazard ratio (HR) was also adjusted for hypertension., Results: The SLE-DM group included 290 patients, of whom 77% were female, compared with 85% of the 2,859 patients in the SLE-non-DM group. SLE-DM patients had a 3 times higher risk of ESRD compared with SLE-non-DM patients (multivariable-adjusted HR 3.3 [95% confidence interval 1.8-6.1]). In stratified multivariable-adjusted analyses, DM increased the rate of ESRD in women and men, patients ≥50 years old at baseline, those with low educational level at baseline, and those with concomitant hypertension., Conclusion: Our findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD compared with SLE patients without DM., (© 2023 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Variations in prevalence and incidence of systemic lupus erythematosus (SLE) within a geographically defined area of central Sweden over a time period of 14 years were examined. Longitudinal differences in disease activity, laboratory test results, and damage accrual were investigated., Methods: Adults (aged ≥18 years) residing in Östergötland County between 2008 and 2021 (mean adult population: 357,000 citizens) with confirmed SLE were identified and followed prospectively until death, December 31, 2021, or emigration. We estimated annual incidence per 100,000 inhabitants stratified by sex and age. Linear regression with year of diagnosis as the outcome assessed whether each clinical measurement at diagnosis varied over time., Results: Prevalence on December 31, 2021, was 71.5 of 100,000 (87% female). One hundred twenty-six new cases were identified during the study period, yielding a mean annual incidence of 3.0 of 100,000 inhabitants; this was higher in females (4.8/100,000) than in males (1.2/100,000). Mean age at diagnosis was 43.7 years (SD 17.3). Age at diagnosis and disease activity measures increased over the calendar year of diagnosis (P < 0.05) whereas disease manifestations, including lupus nephritis, did not vary significantly. Accrual of organ damage was demonstrated over time since diagnosis and stratified by sex, lupus nephritis, and corticosteroid-related damage. Approximately 40% developed damage within 5 years., Conclusion: SLE prevalence and incidence estimates remained constant over 14 years, and disease phenotypes at SLE onset were similar. SLE was diagnosed also among older individuals with a smaller female-to-male ratio. Estimates of prevalence and incidence were comparable to previous Scandinavian reports but lower than observed in registry data from the US and the UK., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: To investigate whether the race and ethnicity of a patient with rheumatoid arthritis (RA) influences rheumatologists' likelihood of choosing to initiate biologic disease-modifying antirheumatic drug (bDMARD) treatment., Methods: We conducted a randomized survey experiment in which identical brief case vignettes of hypothetical patients with RA were sent to US rheumatologists (respondents). Three of the four cases included some level of treatment decision ambiguity whereas the fourth case strongly favored bDMARD initiation. Each respondent was shown the four case vignettes, with the race and ethnicity (Black, Hispanic, White) randomly assigned for each case. Each vignette offered multiple choices for next therapeutic step, which we summarized using frequencies and proportions by race and ethnicity version., Results: Among 159 US rheumatologists, we found that for the three cases with some level of treatment decision ambiguity, there was little to no variability in the proportions of respondents who chose to start a biologic for the Black and Hispanic variants (cases 1, 2, and 3). For case 4, respondents generally agreed to start a biologic with some minimal variability across the variants (92.6% for the Black version, 98.1% for the Hispanic version, and 96.2% for the White version)., Conclusion: There are conflicting data regarding bDMARD use and initiation in patients with RA based on the sex and race of the patient. This work adds to this conversation by examining how the next therapeutic step chosen by rheumatologists varied by the race and ethnicity of the hypothetical patient., (© 2023 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Competing Interests: Conflicts of interest: the authors declare they have no conflicts of interest. This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Minneapolis, MN. The contents of this publication do not necessarily represent the views of the Department of Veterans Affairs or the United States Government.

Objective: Most studies consider either medications ordered or filled, but not both. Medication underuse based on filling data cannot necessarily be ascribed to patient nonadherence. Using both data sources, we quantified primary medication adherence in a cohort of prevalent systemic lupus erythematosus (SLE) pregnancies., Methods: We identified 419 pregnancies in Kaiser Permanente Northern California in patients with prevalent SLE from 2011 to 2020. We calculated the number of physician-initiated orders or pharmacy-initiated reorders during pregnancy and a comparable 9-month window the year before (prepregnancy) and the proportion of orders ever filled and filled within 30 days for hydroxychloroquine (HCQ), azathioprine, and corticosteroids. For pregnancies without an order or reorder, we identified the proportion with previous prescription fills overlapping into the respective study period., Results: New orders for lupus medications were usually filled. HCQ was prescribed most often (45.8% pregnancies) and usually filled (89.7% in prepregnancy, 93.2% during pregnancy). The majority filled within 30 days (80.5% prepregnancy, 83.3% pregnancy). Some pregnancies without new HCQ orders had continuous refills from prior orders; 53% of 2011-2015 pregnancies either had a new order or fill coverage from a previous period, compared to 63.2% of pregnancies delivering in 2016-2019. Corticosteroid fill frequencies were 90.6% in prepregnancy and 83.6% during pregnancy. Fewer patients used azathioprine; however, most new orders were filled (94.3% prepregnancy, 91.7% pregnancy). For azathioprine and corticosteroids, fill rates were modestly higher in prepregnancy compared to pregnancy., Conclusion: We observed that patients have high adherence to filling new orders for lupus medications, such as HCQ and azathioprine, in pregnancy., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Stillbirth, preterm birth, and small for gestational age (SGA) birth have an increased recurrence risk. The occurrence of one of these biologically related outcomes could also increase the risk for another one of these outcomes in a subsequent pregnancy., Objectives: We assessed cross-outcome risks for subsequent stillbirth, preterm birth, and SGA., Methods: We used live birth and fetal death records to identify singleton, sequential birth pairs in California (1997-2017). Stillbirth was defined as delivery at ≥20 weeks of gestation of a foetus that died in utero; preterm birth as live birth at 20-36 weeks; and small for gestational age as sex-specific birthweight <10th percentile for gestational age. Risk ratios (RR) were computed using modified Poisson regression and adjusted for potential confounders. Sensitivity analyses included analysing a cohort restricted to primiparous index births and using inverse-probability censoring weights., Results: Of 3,108,532 birth pairs, 16,668 (0.5%), 260,596 (8.4%) and 331,109 (10.7%) of index births were stillborn, preterm and SGA, respectively. Among individuals with an index stillbirth, the adjusted RRs were 1.90 (95% confidence interval [CI] 1.83, 1.98) for subsequent preterm and 1.35 (95% CI 1.28, 1.41) for subsequent SGA. Among those with index preterm birth, the adjusted RRs were 2.02 (95% CI 1.92, 2.13) for stillbirth and 1.42 (95% CI 1.41, 1.44) for SGA. Among those with index SGA, the adjusted RRs were 1.54 (95% CI 1.46, 1.63) for stillbirth and 1.45 (95% CI 1.44, 1.47) for preterm birth. Similar results were reported for sensitivity analyses., Conclusions: Individuals experiencing stillbirth, preterm birth, or SGA in one pregnancy had an increased risk of one of these biologically related outcomes in a subsequent pregnancy. These findings could encourage enhanced surveillance for individuals who experience stillbirth, preterm birth, or SGA and desire a subsequent pregnancy., (© 2022 John Wiley & Sons Ltd.)

Objective: The chronification of pain is heterogeneous in rheumatology. Chronic overlapping pain conditions (COPCs) such as fibromyalgia, endometriosis, migraine, and back pain may co-occur with one another and in rheumatic diseases. We describe the sociodemographic and clinical profiles associated with concomitant COPCs among patients with rheumatic diseases., Methods: We retrospectively identified patients visiting rheumatology clinics at a single institution from 2010 to 2020 for five common rheumatic conditions: psoriatic arthritis (PsA), rheumatoid arthritis (RA), Sjögren syndrome (SjS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). We compared sociodemographic, clinical, and lifestyle factors by rheumatic condition and by COPC status. We also report sex-stratified diagnosis of COPCs. The primary outcome was diagnostic validation of one or more COPCs., Results: We identified 5992 rheumatology patients: 846 with PsA, 2605 with RA, 956 with SjS, 975 with SLE, and 610 with SSc. Approximately 36-62% of patients had a concomitant COPC diagnosis. Patients with SjS had the highest prevalence (62%). Diagnosis of one or more COPCs was highest among Black patients and lowest among Asian patients. Patients using public insurance had a higher prevalence of one or more COPCs compared with those with private insurance. Patients with one or more COPCs had more depression and anxiety and more frequent emergency department visits, surgeries, and hospitalizations., Conclusion: Our findings suggest that COPCs are strikingly common among patients with rheumatic disease and are associated with lower quality of life and greater health care needs. Future research may elucidate drivers of chronic pain and how to best address the unique analgesic needs of this multimorbid population., (© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: We investigated prolonged COVID-19 symptom duration, defined as lasting 28 days or longer, among people with systemic autoimmune rheumatic diseases (SARDs)., Methods: We analysed data from the COVID-19 Global Rheumatology Alliance Vaccine Survey (2 April 2021-15 October 2021) to identify people with SARDs reporting test-confirmed COVID-19. Participants reported COVID-19 severity and symptom duration, sociodemographics and clinical characteristics. We reported the proportion experiencing prolonged symptom duration and investigated associations with baseline characteristics using logistic regression., Results: We identified 441 respondents with SARDs and COVID-19 (mean age 48.2 years, 83.7% female, 39.5% rheumatoid arthritis). The median COVID-19 symptom duration was 15 days (IQR 7, 25). Overall, 107 (24.2%) respondents had prolonged symptom duration (≥28 days); 42/429 (9.8%) reported symptoms lasting ≥90 days. Factors associated with higher odds of prolonged symptom duration included: hospitalisation for COVID-19 vs not hospitalised and mild acute symptoms (age-adjusted OR (aOR) 6.49, 95% CI 3.03 to 14.1), comorbidity count (aOR 1.11 per comorbidity, 95% CI 1.02 to 1.21) and osteoarthritis (aOR 2.11, 95% CI 1.01 to 4.27). COVID-19 onset in 2021 vs June 2020 or earlier was associated with lower odds of prolonged symptom duration (aOR 0.42, 95% CI 0.21 to 0.81)., Conclusion: Most people with SARDs had complete symptom resolution by day 15 after COVID-19 onset. However, about 1 in 4 experienced COVID-19 symptom duration 28 days or longer; 1 in 10 experienced symptoms 90 days or longer. Future studies are needed to investigate the possible relationships between immunomodulating medications, SARD type/flare, vaccine doses and novel viral variants with prolonged COVID-19 symptoms and other postacute sequelae of COVID-19 among people with SARDs., Competing Interests: Competing interests: MP reports grants from AbbVie—SELECT-GCA Participating Center and AstraZeneca—MANDARA Participating Center; and consulting fees from Novartis, outside the submitted work. ES is a board member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. SES reports research funding related to clinical trials from AstraZeneca (MANDARA) and is supported by the Vasculitis Clinical Research Consortium and Vasculitis Foundation, outside the submitted work. CH is a stockholder for Aurinia Pharmaceuticals; an Advisory Board member for Aurinia Pharmaceuticals, AstraZeneca Pharmaceuticals and UCB Pharmaceuticals; and reports consulting fees from AstraZeneca, UCB, Antidote and Aurinia Pharmaceuticals, outside the submitted work. MJL reports grants from American College of Rheumatology, during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Gilead, Johnson & Johnson, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi and Union Chimique Belge, outside the submitted work. SB reports non-branded consulting fees from AbbVie, Amgen, Horizon Pharma, Novartis and Pfizer outside the submitted work, and is a Pfizer employee as of September 2021. RG reports speaker honoraria from AbbVie New Zealand, Cornerstones and Janssen New Zealand; speaker honoraria and non-financial support Pfizer Australia; non-financial support from Janssen Australia and personal fees from Novartis (all <$A10 000) outside the submitted work. PMM reports consulting fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and Union Chimique Belge; and grants and consulting fees from Orphazyme, outside the submitted work. PCR reports personal fees from AbbVie, Gilead, Eli Lilly and Roche; grants and personal fees from Novartis, Union Chimique Belge, Janssen and Pfizer and non-financial support from Bristol Myers Squibb, outside the submitted work. ZSW reports grants from NIH, Bristol Myers Squibb and Principia/Sanofi; and personal fees from Viela Bio and MedPace, outside the submitted work. JY reports grants from NIH/NIAMS K24 during the conduct of the study and outside the submitted work, reports research grants from Gilead, BMS Foundation and AstraZeneca; consulting fees from Pfizer, AstraZeneca and Aurinia. MG-M reports consulting fees for BMS, BI, JNJ and Aurinia (all <$A10 000), outside the submitted work. RH reports grants from AbbVie, Amgen, Boehringer Ingleheim, Johnson & Johnson, Eli Lilly, Novartis, Pfizer and Union Chimique Belge, all paid to Spondylitis Association of America, and consultant fees from GlaxoSmithKline and Novartis, outside the submitted work. RH also owns stocks (<20 shares and representing <4% of personal investments) in AbbVie, Amgen, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Eli Lilly, Merck, Novartis, Pfizer, Teva and Union Chimique Belge. DA-R is a scientific advisor for and reports personal fees from GlaxoSmithKilne Mexico unrelated to this work. RC reports speaker fees from Janssen, Roche, Sanofi and AbbVie, outside the submitted work. AD-G reports grants from the Centers for Disease Control and Prevention, Rheumatology Research Foundation and Mayo Clinic, outside the submitted work. JAS has received consultant fees from Schipher, Crealta/Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS has received institutional research support from Zimmer Biomet Holdings. JAS received food and beverage payments from Intuitive Surgical/Philips Electronics North America. JAS owns stock options in TPT Global Tech, Vaxart Pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics, Seres Therapeutics, Tonix Pharmaceuticals Holding and Charlotte’s Web Holdings. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker’s bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organisation that develops outcome measures in rheumatology and receives arms-length funding from eight companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Board (FAB). JAS is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. MFU-G reports research grants from Pfizer and Janssen, unrelated to this work. JSH reports grants from and Rheumatology Research Alliance; consulting fees from Novartis, Pfizer and Biogen; and is a member of the Childhood Arthritis and Rheumatology Research Alliance (CARRA). JFS received research grant funding from the National Institutes of Health unrelated to this work (NIAMS R01 AR077103 and NIAID R01 AI154533). JSp is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers R01 AR077607, P30 AR070253 and P30 AR072577), the R. Bruce and Joan M. Mickey Research Scholar Fund, the Llura Gund Award for Rheumatoid Arthritis Research and Care and Bristol Myers Squibb; and personal fees for AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Gilead, Inova Diagnostics, Janssen, Optum and Pfizer, unrelated to this work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD)., Methods: An international study was conducted from 2 April to 16 August 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression., Results: Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95% CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95% CI 1.20, 3.18) and polymyalgia rheumatica (OR 1.94, 95% CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95% CI 0.31-0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95% CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95% CI 1.76, 3.54) and female sex (OR 2.71, 95% CI 1.55, 4.72)., Conclusion: SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts., (Published by Oxford University Press on behalf of the British Society for Rheumatology 2022. This work is written by US Government employees and is in the public domain in the US.)

Objective: To investigate whether obstetric complications prior to systemic sclerosis (SSc) diagnosis are more common in SSc patients compared to the general obstetric population., Methods: A case-control study was performed at Kaiser Permanente Northern California to compare prior obstetric complications in adult women who later developed SSc (cases) with women from the general obstetric population who did not develop SSc (controls; matched 10:1 by age and year of delivery) from 2007 to 2016. Exposures included past hypertensive disorders of pregnancy (preeclampsia, eclampsia, gestational hypertension), premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), maternal infections, neonatal intensive care unit (NICU) admission, and preterm birth. Fischer's exact tests were used to compare categorical variables. Conditional logistic regression models estimated the odds ratio (OR), and corresponding 95% confidence intervals (95% CIs) for the outcome SSc., Results: Seventeen SSc cases and 170 non-SSc controls were identified, with median maternal age at delivery 34 years (range 23-46 years) and median time from delivery to SSc diagnosis 2 years (range 0.2-7.3 years). Women with SSc were more likely to be Hispanic and Black. Prior obstetric complications appeared higher in women with an eventual SSc diagnosis compared to controls (70.6% versus 50%), including hypertensive disorders (17.7% versus 9.4%), PROM (11.8% versus 4.1%), IUGR (5.9% versus 1.8%), maternal infection (29.4% versus 14.1%), NICU admissions (23.5% versus 7.7%), and preterm delivery (29.4% versus 21.8%). Women with SSc had a higher odds of delivering infants requiring NICU admission (OR 4.7 [95% CI 1.2-18.8])., Conclusion: Women who eventually develop SSc had trends toward more complicated pregnancy histories before overt diagnosis., (© 2020 American College of Rheumatology.)

Objective: To investigate the risk of gestational diabetes mellitus (GDM) associated with systemic lupus erythematosus (SLE) by comparing pregnancies in women with SLE to general population controls., Methods: We identified singleton pregnancies among women with SLE and general population controls in the Swedish Medical Birth Register (MBR; 2006-2016), sampled from the population-based Swedish Lupus Linkage (SLINK) cohort (1987-2012). SLE was defined by ≥ 2 International Classification of Diseases (ICD)-coded visits in the National Patient Register (NPR) and MBR, with ≥ 1 visit before pregnancy. GDM was defined by ≥ 1 ICD-coded visit in the NPR or MBR. Glucocorticoid (GC) and hydroxychloroquine (HCQ) dispensations within 6 months before and during pregnancy were identified in the Prescribed Drug Register. Risk ratios (RRs) and 95% CIs of GDM associated with SLE were estimated using modified Poisson regression models, stratified by parity and adjusted for maternal age at delivery, year of birth, and obesity., Results: We identified 695 SLE pregnancies including 18 (2.6%) with GDM and 4644 non-SLE pregnancies including 65 (1.4%) with GDM. Adjusted RRs of GDM associated with SLE were 1.11 (95% CI 0.38-3.27) for first deliveries and 2.03 (95% CI 1.21-3.40) for all deliveries. Among SLE pregnancies, GDM occurred in 7/306 (2.3%) with ≥ 1 GC before and/or during pregnancy, 11/389 (2.8%) without GC, 7/287 (2.4%) with ≥ 1 HCQ before and/or during pregnancy, and in 11/408 (2.7%) without HCQ., Conclusion: When looking at all deliveries, SLE was associated with a 2-fold higher risk of GDM. GDM occurrence did not differ by GC or HCQ., (© 2022 by the Journal of Rheumatology.)

Objective: The objectives of this study were to characterize the reasons for tumor necrosis factor inhibitor (TNFi) initiation in patients with juvenile spondyloarthropathy (JSpA) and identify clinical correlates and to assess the effect of TNFi therapy on JSpA disease activity., Methods: We conducted a retrospective cohort study of 86 patients with JSpA with first-time use of a TNFi over a 7-year period at Stanford Children's Health. We assessed the physician's reason for TNFi initiation, disease activity at 6 months, and clinical disease status at 12 months following TNFi start. Changes in active joint count, enthesitis count, and pain were measured. Demographics, physician reasons for TNFi initiation, and clinical characteristics were summarized., Results: The mean age at JSpA diagnosis was 12.4 years (SD 4.0 years), and the mean time from diagnosis to TNFi initiation was 1.6 years (SD 2.3 years). The most common reason for initiating a TNFi was active disease on physical examination (61%). At 6 months post TNFi initiation, patients on average had three fewer active joints and one fewer active enthesitis point. Patient-reported pain improved from moderate/severe to mild. After 12 months, 54% of patients had active disease., Conclusion: The physician's decision to initiate a TNFi relied mostly on physical examination findings. Despite improvement in arthritis, enthesitis, and patient-reported pain at 6 months post TNFi initiation, the majority of the patients still had active disease after 1 year of therapy., (© 2021 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: The National Standard of Canada for Psychological Health and Safety in the Workplace (the Standard) identifies 13 psychosocial factors affecting psychological health and safety in the workplace that employers should measure and monitor with the goal of addressing areas for improvement. The present study sought to determine the suitability of the Public Service Employee Survey as a tool for the assessment of these psychosocial factors in public service employees. It also aimed to explore-in a preliminary manner-predictors of job satisfaction in these employees., Data and Methods: Data from the 2017 and 2019 Public Service Employee Survey (PSES) were analyzed. Specifically, exploratory structural modelling and tests of measurement invariance were used to identify a measurement model reflecting the psychosocial factors outlined in the Standard and to evaluate the equivalence of this model across both PSES administrations., Results: The analyses uncovered 10 of the 13 psychosocial factors, as well as 2 closely related factors-diversity and inclusion-and supported the full invariance of the resulting measurement model across both PSES administrations. Lastly, preliminary results pointed to recognition and reward (encompassing leader reward behaviours) and involvement and influence (touching on participative decision making, innovation and initiative) as predictors of job satisfaction in both samples of public service employees., Interpretation: The present study identified the PSES as a tool for the assessment-in public service employees-of the majority of the psychosocial factors outlined in the Standard as well as two additional factors of particular importance to the federal government, diversity and inclusion. Future research to address current limitations is discussed, as are preliminary implications for practice.

Objective: Major depressive disorder is the leading cause of disability worldwide. Yet, there remain significant challenges in predicting new cases of major depression and devising strategies to prevent the disorder. An important first step in this process is identifying risk factors for the incidence of major depression. There is accumulating biological evidence linking insulin resistance, another highly prevalent condition, and depressive disorders. The objectives of this study were to examine whether three surrogate measures of insulin resistance (high triglyceride-HDL [high-density lipoprotein] ratio; prediabetes, as indicated by fasting plasma glucose level; and high central adiposity, as measured by waist circumference) at the time of study enrollment were associated with an increased rate of incident major depressive disorder over a 9-year follow-up period and to assess whether the new onset of these surrogate measures during the first 2 years after study enrollment was predictive of incident major depressive disorder during the subsequent follow-up period., Methods: The Netherlands Study of Depression and Anxiety (NESDA) is a multisite longitudinal study of the course and consequences of depressive and anxiety disorders in adults. The study population comprised 601 NESDA participants (18-65 years old) without a lifetime history of depression or anxiety disorders. The study's outcome was incident major depressive disorder, defined using DSM-IV criteria. Exposure measures included triglyceride-HDL ratio, fasting plasma glucose level, and waist circumference., Results: Fourteen percent of the sample developed major depressive disorder during follow-up. Cox proportional hazards models indicated that higher triglyceride-HDL ratio was positively associated with an increased risk for incident major depression (hazard ratio=1.89, 95% CI=1.15, 3.11), as were higher fasting plasma glucose levels (hazard ratio=1.37, 95% CI=1.05, 1.77) and higher waist circumference (hazard ratio=1.11 95% CI=1.01, 1.21). The development of prediabetes in the 2-year period after study enrollment was positively associated with incident major depressive disorder (hazard ratio=2.66, 95% CI=1.13, 6.27). The development of high triglyceride-HDL ratio and high central adiposity (cut-point ≥100 cm) in the same period was not associated with incident major depression., Conclusions: Three surrogate measures of insulin resistance positively predicted incident major depressive disorder in a 9-year follow-up period among adults with no history of depression or anxiety disorder. In addition, the development of prediabetes between enrollment and the 2-year study visit was positively associated with incident major depressive disorder. These findings may have utility for evaluating the risk for the development of major depression among patients with insulin resistance or metabolic pathology.

Objective: Immune dysregulation in SLE and the corresponding immune-modulating and immunosuppressive nature of the treatments may play key roles in infection risk. We compared serious infection rates among individuals with incident SLE with the general population, and examined the role of treatment initiation in SLE., Methods: Newly diagnosed patients with SLE (2006-2013) and general population comparators from the Swedish Lupus Linkage cohort were followed for serious infection through 2016. Adjusted Cox and frailty models estimated the relative risk of first and recurrent infections, respectively. Using a new-user design, rates of serious infections were compared between disease-modifying antirheumatic drugs (DMARDs) and hydroxychloroquine (HCQ) initiators. We then evaluated three DMARDs (azathioprine, mycophenolate mofetil and methotrexate) in multivariable-adjusted models., Results: Individuals with SLE experienced more infections (22% vs 6%), especially during the first year of follow-up, and recurrent serious infections were also more common (HR=2.22, 95% CI 1.93 to 2.56). DMARDs were associated with a higher rate of serious infection versus HCQ (HR=1.82, 95% CI 1.27 to 2.60), which attenuated after multivariable-adjustment (HR=1.30, 95% CI 0.86 to 1.95). Among DMARDs, azathioprine was associated with infection (HR=2.19, 95% CI 1.14 to 4.21) and mycophenolate mofetil yielded an HR=1.39 (95% CI 0.65 to 2.96) in multivariable-adjusted models compared with methotrexate. Results were comparable across numerous sensitivity analyses., Conclusion: Individuals with incident SLE were 2-4 times more likely to be hospitalised for infection and experienced more recurrent infections than the general population. Among DMARD initiators, azathioprine was associated with the highest rate., Competing Interests: Competing interests: MR reports non-promotional speaker fees from Teva, outside of this work., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)