Julia Fridman Simard

All Publications

• Lipodermatosclerosis and Pulmonary Hypertension in Systemic Sclerosis. JAMA dermatology Davuluri, S., Kapoor, P., Nandyala, S., Li, S., Simard, J., Lewis, M., Fiorentino, D., Chung, L. 2024

  Abstract

  Lipodermatosclerosis (LDS) stems from vascular dysfunction and dermal inflammation and thereby is mechanistically similar to systemic sclerosis (SSc). The association of LDS with SSc in the clinical setting has not been well characterized in the literature.To evaluate the prevalence of LDS in SSc and the association of LDS with vascular complications, particularly pulmonary hypertension, in patients with SSc.This retrospective cohort study used prospectively collected longitudinal data from a cohort of patients from the multidisciplinary rheumatology and dermatology clinic at a single tertiary care center from November 2004 to November 2022. Adult patients (aged ≥18 years at the time of cohort entry) with SSc were included.Clinical diagnosis of LDS based on expert opinion or histopathologic findings.The main outcomes included prevalence of LDS, the association of LDS with the macrovascular complications, including pulmonary hypertension, digital gangrene and/or scleroderma renal crisis. Disease complications, including cardiac arrhythmias and heart failure, were compared among patients with and without LDS.Among 567 patients with SSc (494 [87.1%] female; mean [SD] age, 53.4 [14.4] years), 25 (4.4%) had LDS and 542 (95.6%) did not have LDS. Skin ulceration occurred in 8 patients with LDS (32.0%). Patients with LDS had higher frequencies of cardiac arrhythmia (11 of 24 [45.8%] vs 145 of 539 [26.9%]), heart failure (7 [28.0%] vs 55 [10.1%]), and pulmonary hypertension (12 [48.0%] vs 137 of 541 [25.3%]) compared with patients without LDS. Frequency of scleroderma renal crisis and digital gangrene did not differ significantly between patients with and without LDS (0 vs 37 [6.8%] and 4 [16.0%] vs 69 of 538 [12.8%], respectively). Among patients with LDS, 9 (36.0%) were either discharged to hospice or died during follow-up compared with 115 patients without LDS (21.2%). Lipodermatosclerosis was associated with pulmonary hypertension (adjusted prevalence odds ratio, 3.10; 95% CI, 1.33-7.25).In this cohort study, LDS was a rare clinical manifestation in patients with SSc but was associated with pulmonary hypertension. Therefore, patients with LDS should be closely monitored and screened for pulmonary hypertension.

  View details for DOI 10.1001/jamadermatol.2024.3929

  View details for PubMedID 39412798

• A Hidden Workflow Inequity of Penicillin Allergy Evaluation in Pregnancy. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology Dunham, T. B., Zhu, L., Lee, J. H., Sperling, M., Hoyte, E., Gibbs, R., Liu, A. Y., Simard, J. F. 2024

  View details for DOI 10.1016/j.anai.2024.09.017

  View details for PubMedID 39370037

• Anti-SARS-CoV-2 mRNA vaccination among patients living with SLE in Sweden: Coverage and clinical effectiveness. Lupus Mageau, A., Simard, J. F., Svenungsson, E., Arkema, E. V. 2024: 9612033241273052

  Abstract

  To describe the uptake of anti-SARS-CoV2 vaccination in 2021 and investigate vaccine effectiveness in systemic lupus erythematosus (SLE) patients in Sweden.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.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.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.

  View details for DOI 10.1177/09612033241273052

  View details for PubMedID 39133903

• A Counterfactual Analysis of Impact of Cesarean Birth in a First Birth on Severe Maternal Morbidity in the Subsequent Birth. Epidemiology (Cambridge, Mass.) Bane, S., Snowden, J. M., Simard, J. F., Odden, M., Kan, P., Main, E. K., Carmichael, S. L. 2024

  Abstract

  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.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.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.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.

  View details for DOI 10.1097/EDE.0000000000001775

  View details for PubMedID 39058553

• Misdiagnosis, missed diagnosis and delayed diagnosis of lupus: A qualitative study of rheumatologists. Arthritis care & research Bane, S., Falasinnu, T., Rodriguez Espinosa, P., Simard, J. F. 2024

  Abstract

  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.We conducted 41 semi-structured interviews among U.S. 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.Participants were 66% women and 49% had >10 years of post-fellowship experience. Five major themes were generated, including receiving training through the lens of race or gender, the role of the documented epidemiology of SLE, pattern recognition and test-taking strategies, case 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.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.

  View details for DOI 10.1002/acr.25405

  View details for PubMedID 39037219

• Considering pregnancies as repeated versus independent events: An empirical comparison of common approaches across selected perinatal outcomes. American journal of obstetrics & gynecology MFM Bane, S., Carmichael, S. L., Mathur, M. B., Simard, J. F. 2024: 101434

  Abstract

  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 (e.g., missing parity information). These decisions determine how appropriately a given research question can be answered and overall generalizability.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 (i.e., we did not sample all births by a given mother, but rather sampled individual births). Study outcomes were severe maternal morbidity 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 for the associations of outcomes with independent variables. Among all-births, we then compared risk ratios 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.We observed minor differences in the population characteristics between the all-birth (N=2,736,693), random-selection, and first-observed birth cohorts (both N=2,284,660), with more substantial differences between these cohorts and the primiparous-births cohort (N=1,054,684). Outcome prevalence was consistently lowest among all-births and highest among primiparous-births (e.g., severe maternal morbidity 18.9 per 1,000 births among primiparous-births vs. 16.6 per 1,000 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. Risk ratios 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, i.e., crude estimates (e.g., lupus-severe maternal morbidity association: 4.01, 95% CI 3.54-4.55 vs. 4.01, 95% CI 3.53-4.56 for crude estimate), while adjusting for parity slightly shifted estimates, towards the null for severe maternal morbidity and away from the null for preeclampsia/eclampsia.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.

  View details for DOI 10.1016/j.ajogmf.2024.101434

  View details for PubMedID 38996915

• Increased Risk of Preterm Delivery Subtypes and Hypertensive Disorders of Pregnancy in First Deliveries of Patients With Systemic Vasculitis. ACR open rheumatology Horomanski, A., Mayo, J., Shaw, G. M., Simard, J. F. 2024

  Abstract

  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.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.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).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.

  View details for DOI 10.1002/acr2.11702

  View details for PubMedID 38970474

• Hydroxychloroquine and Preeclampsia in a Diverse Cohort of Women with SLE. Arthritis care & research Simard, J. F., Liu, E. F., Rector, A., Cantu, M., Chakravarty, E., Druzin, M., Kuo, D. Z., Shaw, G. M., Weisman, M., Hedderson, M. 2024

  Abstract

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

  View details for DOI 10.1002/acr.25386

  View details for PubMedID 38926748

• Impact of Incentives on Physician Participation in Research Surveys: Randomized Experiment. JMIR formative research Hawa, S., Bane, S., Kinsler, K., Rector, A., Chaichian, Y., Falasinnu, T., Simard, J. F. 2024; 8: e54343

  Abstract

  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.This study aims to conduct a randomized study to assess how different incentive amounts influenced survey participation among neurologists in the United States.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.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).As expected, monetary incentives can boost physician survey participation and completion, with a positive correlation between the amount offered and participation.

  View details for DOI 10.2196/54343

  View details for PubMedID 38743466

• Feedback Loop Failure Modes in Medical Diagnosis: How Biases Can Emerge and Be Reinforced. Medical decision making : an international journal of the Society for Medical Decision Making Aikens, R. C., Chen, J. H., Baiocchi, M., Simard, J. F. 2024: 272989X241248612

  Abstract

  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.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.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.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.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.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.

  View details for DOI 10.1177/0272989X241248612

  View details for PubMedID 38738479

• Prognostic Value of the 2019 EULAR/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria to Renal Response One Year After Treatment in a Cohort With Childhood-Onset Lupus Nephritis. ACR open rheumatology Patrizi, S. T., Tandel, M. D., Boothroyd, D., Simard, J. F., Hsu, J. J. 2024

  Abstract

  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.

  View details for DOI 10.1002/acr2.11674

  View details for PubMedID 38695166

• Sick leave and disability pension following delivery in women with systemic lupus erythematosus. Scandinavian journal of rheumatology Grannas, D., Simard, J. F., Svenungsson, E., Arkema, E. V., Gernaat, S. 2024; 53 (3): 199-206

  Abstract

  OBJECTIVE: To investigate sickness benefits following delivery in mothers with systemic lupus erythematosus (SLE) and mothers without SLE.METHOD: SLE and non-SLE mothers, matched by age and month of delivery, with a singleton liveborn (2004-2008), were identified from the Swedish Lupus Linkage cohort. Work loss (sum of sick leave and disability pension) was studied from 1 year prenatally to 3years postpartum. Adjusted logistic regression models of covariates associated with >30days of work loss in the first and second years postpartum were estimated in SLE mothers.RESULTS: Among 130 SLE mothers and 440 non-SLE mothers, SLE mothers were more likely to have work loss from the prenatal year (42% vs 16%) to 3years postpartum (49% vs 15%). In SLE mothers, work loss was on average 61±112days (mean ±sd) in the prenatal year and 38±83 days in the first year postpartum, which increased to 71±114 days in the third year postpartum. Having >30days of sick leave in the year of delivery [odds ratio (OR) 4.4, 95% confidence interval (CI) 1.5-12.9] and ≤12years of education (OR 2.6, 95% CI 1.1-6.0) were associated with work loss in the first year postpartum. No covariates were associated with work loss in the second year postpartum.CONCLUSION: SLE mothers more often had work loss in the prenatal year to 3years postpartum compared to non-SLE mothers. Lower education and sick leave in the year of delivery were associated with a higher odds of work loss in the first year postpartum in SLE.

  View details for DOI 10.1080/03009742.2024.2321057

  View details for PubMedID 38607692

• The Problem of Pain in Lupus: Epidemiological Profiles of Patients Attending Multidisciplinary Pain Clinics. Pain management nursing : official journal of the American Society of Pain Management Nurses Jiang, T. E., Pascual, A. P., Le, N., Nguyen, T. B., Mackey, S., Darnall, B. D., Simard, J. F., Falasinnu, T. 2024

  Abstract

  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.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.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.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.

  View details for DOI 10.1016/j.pmn.2024.02.012

  View details for PubMedID 38494346

• Hydroxychloroquine in lupus or rheumatoid arthritis pregnancy and risk of major congenital malformations: a population-based cohort study. Rheumatology (Oxford, England) Nguyen, N. V., Svenungsson, E., Dominicus, A., Altman, M., Hellgren, K., Simard, J. F., Arkema, E. V. 2024

  Abstract

  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.

  View details for DOI 10.1093/rheumatology/keae168

  View details for PubMedID 38479815

• Referral Patterns and Uptake of Penicillin Delabeling in Pregnancy Dunham, T., Zhu, L., Lee, J., Sperling, M., Hoyte, E., Gibbs, R., Simard, J., Liu, A. MOSBY-ELSEVIER. 2024: AB164

  View details for Web of Science ID 001267526000508

• Hydroxychloroquine in lupus pregnancy and risk of preeclampsia. Arthritis & rheumatology (Hoboken, N.J.) Rector, A., Maric, I., Chaichian, Y., Chakravarty, E., Cantu, M., Weisman, M. H., Shaw, G. M., Druzin, M., Simard, J. F. 2024

  Abstract

  OBJECTIVE: Systemic lupus (SLE) disproportionately affects females during childbearing years, and hydroxychloroquine (HCQ) is the standard first-line treatment. Preeclampsia complicates up to one-third of lupus pregnancies, although reports vary by parity and multi-fetal gestation. We investigated whether HCQ use early in pregnancy may reduce the risk of preeclampsia.METHODS: We studied 1068 livebirth singleton pregnancies among 1020 privately insured patients with SLE (2007-2016). HCQ use was defined as 3 months preconception through the first trimester and prescription fills were a proxy for use. Modified Poisson regression estimated risk ratios (RRs) and 95% confidence intervals (95% CI) stratified by parity. Propensity scores accounted for confounders and stratified analyses examined effect modification.RESULTS: Approximately 15% of pregnancies were diagnosed with preeclampsia. 52% of pregnancies had ≥1 HCQ fill. HCQ-exposed pregnancies had more comorbidities, SLE activity, and azathioprine use. 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 control for confounding decreased the RRs towards the null (nulliparous: PS-adj RR=1.09, 95% CI 0.68, 1.76 and multiparous: 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 use 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 SLE pregnancy and among persons at greater risk of hypertensive disorders of pregnancy.

  View details for DOI 10.1002/art.42793

  View details for PubMedID 38272838

• Pregnancy outcomes in a diverse US Lupus Cohort. Arthritis care & research Simard, J. F., Liu, E. F., Chakravarty, E., Rector, A., Cantu, M., Kuo, D. Z., Shaw, G. M., Druzin, M. L., Weisman, M. H., Hedderson, M. M. 2024

  Abstract

  OBJECTIVE: Although the systemic lupus (SLE) patient population is racially and ethnically diverse, many study populations are homogeneous. Further, data are often lacking on critical factors such as antiphospholipid (aPL) antibodies. We investigated livebirth rates in patients with SLE at Kaiser Permanente Northern California including race/ethnicity and aPL data.METHODS: Electronic health records of pregnancies with outcomes observed from 2011-2020 were identified among patients with SLE. Prevalent SLE was defined as ≥2 ICD coded visits ≥7days apart before the last menstrual period (LMP). We summarized patient characteristics, medication orders, and healthcare utilization, and medication use. Pregnancy outcomes (livebirth, stillbirth, spontaneous abortion, ectopic, molar) were presented overall, and stratified by race/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 (NH) White, 13% NH Black, 5% Multiracial, about 2% Islander, Native American). Approximately 74% of observed pregnancies ended in livebirth, 23% resulted in spontaneous abortion, 2% were ectopic or molar pregnancies, and <1% were stillbirths. There was limited variability in livebirths by race/ethnic group (72%-79%), aPL (69.5%-77%), and nephritis (71%-75%) CONCLUSION: Our findings are consistent with previous studies, however, some methodologic differences may yield a range of livebirth rates. We found that approximately 74% of pregnancies in SLE ended in livebirth, with modest variability in spontaneous abortion by race/ethnicity, nephritis, and aPL.

  View details for DOI 10.1002/acr.25279

  View details for PubMedID 38221659

• The Problem of Pain in Rheumatology: Variations in Case Definitions Derived From Chronic Pain Phenotyping Algorithms Using Electronic Health Records. The Journal of rheumatology Falasinnu, T., Nguyen, T., En Jiang, T., Tamang, S., Chaichian, Y., Darnall, B. D., Mackey, S., Simard, J. F., Chen, J. H. 2023

  Abstract

  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.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.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.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.

  View details for DOI 10.3899/jrheum.2023-0416

  View details for PubMedID 38101917

• Assessing Biases in Medical Decisions via Clinician and AI Chatbot Responses to Patient Vignettes. JAMA network open Kim, J., Cai, Z. R., Chen, M. L., Simard, J. F., Linos, E. 2023; 6 (10): e2338050

  View details for DOI 10.1001/jamanetworkopen.2023.38050

  View details for PubMedID 37847506

• Hydroxychloroquine and Preeclampsia Risk in Lupus Pregnancy: Results from a Large Regional Integrated Health Network Simard, J., Liu, E., Rector, A., Cantu, M., Kuo, D., Chakravarty, E., Druzin, M., Shaw, G., Weisman, M., Hedderson, M. WILEY. 2023: 912-913

  View details for Web of Science ID 001190014300470

• Incident Vascular Events in Danish Nationwide Cohort of Patients with Newly Diagnosed Systemic Lupus Erythematosus Hansen, R., Simard, J., Faurschou, M., Jacobsen, S. WILEY. 2023: 2844-2845

  View details for Web of Science ID 001190014302441

• Anti-SARS-CoV-2 Vaccination Among Patients Living with Systemic Lupus Erythematosus in Sweden: Coverage and Clinical Effectiveness Mageau, A., Simard, J., Svenungsson, E., Arkema, E. WILEY. 2023: 4530-4532

  View details for Web of Science ID 001190014304337

• Pregnancy Outcomes Among Patients with Vasculitis Using Administrative Claims Data Rector, A., Simard, J., Shaw, G., Horomanski, A. WILEY. 2023: 4801-4803

  View details for Web of Science ID 001190014305027

• A Novel Association Between Lipodermatosclerosis and Key Vascular Outcomes in Systemic Sclerosis Davuluri, S., Kapoor, P., Nandyala, S., Fiorentino, D., Simard, J., Chung, L. WILEY. 2023: 1306-1309

  View details for Web of Science ID 001190014301148

• Reproductive Health Conversations with a Primarily Hispanic Systemic Lupus Erythematosus Population: Influences and Barriers Zaheer, Z., Delgado, M., Rodman, J., Simard, J., Lee, S., Wise, L. WILEY. 2023: 373-376

  View details for Web of Science ID 001190014300195

• Reproductive Health Discussions Between Rheumatology Providers and Systemic Lupus Erythematosus Patients: A Survey of English and SpanishSpeaking Patients Xepoleas, M., Delgado, M., Rodman, J., Simard, J., Lee, S., Wise, L. WILEY. 2023: 368-370

  View details for Web of Science ID 001190014300192

• ''Racial and ethnic differences in prescribing patterns for Psoriasis: a survey of 525 US dermatologists'' Petion, E., van Egmond, S., Hunt, I., Zadu, A., Junko, T., Simard, J., Lester, J., Linos, E. MOSBY-ELSEVIER. 2023: AB7

  View details for Web of Science ID 001078492800020

• Prescribing Patterns for Acne in Transgender Compared to Cisgender Patients Zadu, A., van Egmond, S., Hunt, I., Linos, E., Petion, E., Yeung, H., Simard, J., Cai, Z. MOSBY-ELSEVIER. 2023: AB5

  View details for Web of Science ID 001078492800018

• Trends in adverse pregnancy outcomes among women with systemic sclerosis in the United States. Seminars in arthritis and rheumatism Kawano, Y., Kolstad, K. D., Li, S., Simard, J. F., Chung, L. 2023; 63: 152252

  Abstract

  We sought to examine temporal trends in adverse pregnancy outcomes among SSc pregnancies in a large nationwide sample.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.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.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.

  View details for DOI 10.1016/j.semarthrit.2023.152252

  View details for PubMedID 37666113

• Epidemiology and Damage Accrual of Systemic Lupus Erythematosus in Central Sweden: A Single-Center Population-Based Cohort Study Over 14 Years From Östergötland County. ACR open rheumatology Arkema, E. V., Saleh, M., Simard, J. F., Sjöwall, C. 2023

  Abstract

  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.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.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.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.

  View details for DOI 10.1002/acr2.11585

  View details for PubMedID 37469135

• Biologics Initiation in Rheumatoid Arthritis by Race and Ethnicity: Results From a Randomized Survey Study. ACR open rheumatology Simard, J. F., Lu, R., Falasinnu, T. O., Baker, M. C., Hawa, S., Deluna, M. D., Horomanski, A., Fairchild, R. M. 2023

  Abstract

  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.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.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).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.

  View details for DOI 10.1002/acr2.11573

  View details for PubMedID 37312437

• HYDROXYCHLOROQUINE USE IN PREGNANT WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND MAJOR CONGENITAL MALFORMATIONS IN THE OFFSPRING Nguyen, N. V., Svenungsson, E., Dominicus, A., Hellgren, K., Simard, J., Arkema, E. BMJ PUBLISHING GROUP. 2023: 890

  View details for DOI 10.1136/annrheumdis-2023-eular.894

  View details for Web of Science ID 001107398703033

• The data giveth, but what do we take away? Paediatric and perinatal epidemiology Simard, J. F., Palmsten, K. 2023

  View details for DOI 10.1111/ppe.12975

  View details for PubMedID 37012652

• Risk of End-stage Renal Disease in Patients with Systemic Lupus Erythematosus and Diabetes Mellitus: Danish Nationwide Cohort Study. Arthritis care & research Hansen, R. B., Falasinnu, T., Faurschou, M., Jacobsen, S., Simard, J. F. 2023

  Abstract

  OBJECTIVES: The risk of end-stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). We estimated whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of patients with SLE.METHODS: By means of the Danish National Patient Register (DNPR), we identified 3178 adult patients diagnosed with 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 in DNPR of dialysis, renal transplant, or terminal renal insufficiency. 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. Overall HR was also adjusted for hypertension.RESULTS: The SLE-DM group included 290 patients of whom 77% were female, compared with 85% of the 2859 in the SLE-non-DM group. SLE-DM patients had three times higher risk of ESRD compared with SLE-non-DM patients (multivariable-adjusted HR=3.3 [95% CI: 1.8-6.1]). In stratified multivariable-adjusted analyses, DM increased the rate of ESRD in women and men, patients aged ≥50years at baseline, those with low educational level at baseline and concomitant hypertension.CONCLUSION: Our findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD than SLE patients without DM.

  View details for DOI 10.1002/acr.25091

  View details for PubMedID 36705445

• The perspectives of 606 US dermatologists on active surveillance for low-risk basal cell carcinoma. The British journal of dermatology van Egmond, S., de Vere Hunt, I., Cai, Z. R., Rizk, N., Wakkee, M., Chren, M., Goldfarb, N., Simard, J. F., Linos, E. 2023; 188 (1): 136-137

  View details for DOI 10.1093/bjd/ljac002

  View details for PubMedID 36689496

• Reconciling Between Medication Orders and Medication Fills for Lupus in Pregnancy. ACR open rheumatology Simard, J. F., Liu, E. F., Chakravarty, E., Rector, A., Cantu, M., Kuo, D. Z., Shaw, G. M., Druzin, M., Weisman, M. H., Hedderson, M. M. 2022

  Abstract

  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 30days 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 30days (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.

  View details for DOI 10.1002/acr2.11501

  View details for PubMedID 36252776

• Primary hydroxychloroquine adherence in lupus pregnancy Simard, J. F., Liu, E. F., Chakravarty, E., Rector, A., Cantu, M., Kuo, D., Shaw, G., Druzin, M., Weisman, M., Hedderson, M. WILEY. 2022: 125

  View details for Web of Science ID 000859084400242

• The Problem of Pain in Rheumatology: Clinical Profiles Associated with Concomitant Diagnoses with Chronic Overlapping Pain Conditions Falasinnu, T., Chaichian, Y., Simard, J. WILEY. 2022: 2392-2394

  View details for Web of Science ID 000877386502229

• Increased Risk of Preterm Delivery Phenotypes and Hypertensive Disorders of Pregnancy in First Deliveries of Patients with Systemic Vasculitis Horomanski, A., Shaw, G., Mayo, J., Simard, J. WILEY. 2022: 1880-1881

  View details for Web of Science ID 000877386501467

• Assessing the Association Between Hydroxychloroquine and Preeclampsia Risk in SLE Pregnancies Using Administrative Claims Data Rector, A., Maric, I., Chaichian, Y., Chakravarty, E., Cantu, M., Weisman, M., Shaw, G., Druzin, M., Simard, J. WILEY. 2022: 1890-1893

  View details for Web of Science ID 000877386501473

• Exploring Reasons for Non-Use of Hydroxychloroquine in SLE Pregnancy Chan, A., Hirz, A., Chaichian, Y., Rector, A., Druzin, M., Simard, J. WILEY. 2022: 1901-1902

  View details for Web of Science ID 000877386501477

• Pregnancy Outcomes in a Diverse Lupus Cohort Simard, J., Liu, E., Chakravarty, E., Rector, A., Cantu, M., Kuo, D., Shaw, G., Druzin, M., Weisman, M., Hedderson, M. WILEY. 2022: 1905-1906

  View details for Web of Science ID 000877386501479

• Prolonged COVID-19 symptom duration in people with systemic autoimmune rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey. RMD open DiIorio, M., Kennedy, K., Liew, J. W., Putman, M. S., Sirotich, E., Sattui, S. E., Foster, G., Harrison, C., Larche, M. J., Levine, M., Moni, T. T., Thabane, L., Bhana, S., Costello, W., Grainger, R., Machado, P. M., Robinson, P. C., Sufka, P., Wallace, Z. S., Yazdany, J., Gore-Massy, M., Howard, R. A., Kodhek, M. A., Lalonde, N., Tomasella, L., Wallace, J., Akpabio, A., Alpizar-Rodriguez, D., Beesley, R. P., Berenbaum, F., Bulina, I., Chock, E. Y., Conway, R., Duarte-Garcia, A., Duff, E., Gheita, T. A., Graef, E. R., Hsieh, E., El Kibbi, L., Liew, D. F., Lo, C., Nudel, M., Singh, A. D., Singh, J. A., Singh, N., Ugarte-Gil, M. F., Hausmann, J. S., Simard, J. F., Sparks, J. A. 2022; 8 (2)

  Abstract

  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.

  View details for DOI 10.1136/rmdopen-2022-002587

  View details for PubMedID 36104117

• 529 dermatologists' perspectives on active surveillance for low-risk basal cell carcinoma van Egmond, S., Hunt, I., Cai, Z., Rizk, N., Wakkee, M., Chren, M., Goldfarb, N., Simard, J., Linos, E. ELSEVIER SCIENCE INC. 2022: S64

  View details for Web of Science ID 000829693000549

• The Problem of Pain in Rheumatology: Clinical Profiles Associated With Concomitant Diagnoses With Chronic Overlapping Pain Conditions. ACR open rheumatology Falasinnu, T., Nguyen, T., Jiang, T. E., Chaichian, Y., Rector, A., Darnall, B. D., Mackey, S., Simard, J. F. 2022

  Abstract

  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), Sjogren 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.

  View details for DOI 10.1002/acr2.11488

  View details for PubMedID 35872631

• Baseline Factors Associated with Self-reported Disease Flares Following COVID-19 Vaccination among Adults with Systemic Rheumatic Disease: Results from the COVID-19 Global Rheumatology Alliance Vaccine Survey. Rheumatology (Oxford, England) Rider, L. G., Parks, C. G., Wilkerson, J., Schiffenbauer, A. I., Kwok, R. K., Noroozi Farhadi, P., Nazir, S., Ritter, R., Sirotich, E., Kennedy, K., Larche, M. J., Levine, M., Sattui, S. E., Liew, J. W., Harrison, C. O., Moni, T. T., Miller, A. K., Putman, M., Hausmann, J., Simard, J. F., Sparks, J. A., Miller, F. W., COVID-19 Global Rheumatology Alliance Vaccine Survey Group Akpabio, Akpabio, A. A., Alpizar-Rodriguez, D., Berenbaum, F., Bulina, I., Conway, R., Singh, A. D., Duff, E., Durrant, K., Gheita, T. A., Hill, C. L., Howard, R., Hoyer, B. F., Hsieh, E., El Kibbi, L., Kilian, A., Kim, A. H., Liew, D., Lo, C., Miller, B., Mingolla, S., Nudel, M., Palmerlee, C. A., Singh, J. A., Singh, N., Ugarte-Gil, M. F., Wallace, J., Young, K. J., Bhana, S., Costello, W., Grainger, R., Machado, P. M., Robinson, P. C., Sufka, P., Wallace, Z. S., Yazdany, J., Foster, G., Thabane, L., Angevare, S., Beesley, R. P., Chock, E., Degirmenci, B., Felix, C., Jin, S., Mateus, E., Peirce, A., Sari, E., Tseng, R., Wang, L., Zamora, E. A. 2022

  Abstract

  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 April 2 to August 16, 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.

  View details for DOI 10.1093/rheumatology/keac249

  View details for PubMedID 35460240

• Subsequent risk of stillbirth, preterm birth, and small for gestational age: A cross-outcome analysis of adverse birth outcomes. Paediatric and perinatal epidemiology Bane, S., Simard, J. F., Wall-Wieler, E., Butwick, A. J., Carmichael, S. L. 2022

  Abstract

  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 ≥20weeks of gestation of a foetus that died in utero; preterm birth as live birth at 20-36weeks; 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%CI1.41, 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.

  View details for DOI 10.1111/ppe.12881

  View details for PubMedID 35437809

• COVID-19 vaccine perceptions and uptake: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey. The Lancet. Rheumatology Putman, M., Kennedy, K., Sirotich, E., Liew, J. W., Sattui, S. E., Moni, T. T., Akpabio, A. A., Alpizar-Rodriguez, D., Angevare, S., Beesley, R. P., Berenbaum, F., Bulina, I., Chock, Y. P., Conway, R., Duarte-Garcia, A., Singh, A. D., Duff, E., Durrant, K. L., Gheita, T. A., Hill, C. L., Howard, R., Hoyer, B. F., Hsieh, E., El Kibbi, L., Kilian, A., Kim, A. H., Liew, D. F., Lo, C., Mateus, E. F., Miller, B., Mingolla, S., Nudel, M., Singh, J. A., Singh, N., Ugarte-Gil, M. F., Wallace, J., Young, K. J., Zamora-Tehozol, E. A., Bhana, S., Costello, W., Grainger, R., Machado, P. M., Robinson, P. C., Sufka, P., Wallace, Z. S., Yazdany, J., Harrison, C., Larche, M. J., Levine, M., Foster, G., Thabane, L., Hausmann, J. S., Sparks, J. A., Simard, J. F. 2022

  View details for DOI 10.1016/S2665-9913(22)00001-7

  View details for PubMedID 35156060

• Gestational Diabetes Mellitus Risk in Pregnant Women with Systemic Lupus Erythematosus. The Journal of rheumatology Gernaat, S. A., Simard, J. F., Wikstrom, A., Svenungsson, E., Arkema, E. V. 2021

  Abstract

  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 populationbased register linkage SLINK (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 6 months before and during pregnancy were identified in the Prescribed Drug Register. Risk ratios and 95% confidence intervals (RRs; 95% CI) 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 4,644 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 two-fold higher risk of GDM. GDM occurrence did not differ by GC or HCQ.

  View details for DOI 10.3899/jrheum.210087

  View details for PubMedID 34853085

• Determinants of Tumor Necrosis Factor Inhibitor Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomes. ACR open rheumatology Oliver, M., Simard, J. F., Lee, T., Gerstbacher, D., Sandborg, C. 2021

  Abstract

  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 12.4years (SD 4.0years), and the mean time from diagnosis to TNFi initiation was 1.6years (SD 2.3years). 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.

  View details for DOI 10.1002/acr2.11353

  View details for PubMedID 34647693

• Incident Major Depressive Disorder Predicted by Three Measures of Insulin Resistance: A Dutch Cohort Study. The American journal of psychiatry Watson, K. T., Simard, J. F., Henderson, V. W., Nutkiewicz, L., Lamers, F., Nasca, C., Rasgon, N., Penninx, B. W. 2021: appiajp202120101479

  Abstract

  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.

  View details for DOI 10.1176/appi.ajp.2021.20101479

  View details for PubMedID 34551583

• Vaccine exposure during pregnancy among privately and publicly insured women in the United States, 2016-2018. Vaccine Moll, K., Wong, H., Fingar, K., Ke Zhou, C., Lu, M., Hu, M., Hobbi, S., Burrell, T., Baer, B., Simard, J., Obidi, J., Chillarige, Y., MaCurdy, T., Anderson, S., Shoaibi, A. 2021

  Abstract

  BACKGROUND: Vaccine use during pregnancy affects maternal and infant health. Many women do not receive vaccines recommended during pregnancy; conversely, inadvertent exposure to vaccines contraindicated or not recommended during pregnancy may occur. We assessed exposure to two recommended vaccines and two vaccines not recommended during pregnancy among privately and Medicaid-insured women in the United States.METHODS: This study includes a retrospective cohort of pregnancies in women aged 12-55years resulting in live birth, spontaneous abortion, or stillbirth identified in the IBM MarketScan Commercial, Blue Health Intelligence (BHI) Commercial, and IBM MarketScan Multi-State Medicaid Databases from August 1, 2016, to December 31, 2018. Gestational age at vaccination was determined using a validated algorithm. We examined vaccines (1) recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) (tetanus, diphtheria, and acellular pertussis [Tdap]; inactivated influenza) and (2) not recommended (human papillomavirus [HPV]) or contraindicated (measles, mumps, and rubella [MMR]).RESULTS: We identified 496,771 (MarketScan Commercial), 858,961 (BHI), and 289,573 (MarketScan Medicaid) pregnancies (approximately 75% aged 20-34years). Across these three databases, 52.1%, 50.3%, and 31.3% of pregnancies, respectively, received Tdap, most often at a gestational age of 28weeks, and influenza vaccination occurred in 32.1%, 30.8%, and 18.0% of pregnancies, respectively. HPV vaccination occurred in<0.2% of pregnancies, mostly in the first trimester among women aged 12-19years, and MMR was administered in<0.1% of pregnancies. Use of other contraindicated vaccines per ACIP (e.g., varicella, live attenuated influenza) was rare.CONCLUSION: Maternal vaccination with ACIP-recommended vaccines was suboptimal among privately and Medicaid-insured patients, with lower vaccination coverage among Medicaid-insured pregnancies than their privately insured counterparts. Inadvertent exposure to contraindicated vaccines during pregnancy was rare. This study evaluated only vaccinations reimbursed among insured populations and may have limited generalizability to uninsured populations.

  View details for DOI 10.1016/j.vaccine.2021.08.091

  View details for PubMedID 34507857

• Trends in Adverse Pregnancy Outcomes Among Women with Systemic Sclerosis in the United States Kawano, Y., Kolstad, K., Li, S., Simard, J., Chung, L. WILEY. 2021: 3077-3079

  View details for Web of Science ID 000744545206031

• Infection hospitalisation in systemic lupus in Sweden. Lupus science & medicine Simard, J. F., Rossides, M., Gunnarsson, I., Svenungsson, E., Arkema, E. V. 2021; 8 (1)

  Abstract

  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.

  View details for DOI 10.1136/lupus-2021-000510

  View details for PubMedID 34526357

• Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey. RMD open Sattui, S. E., Liew, J. W., Kennedy, K., Sirotich, E., Putman, M., Moni, T. T., Akpabio, A., Alpizar-Rodriguez, D., Berenbaum, F., Bulina, I., Conway, R., Singh, A. D., Duff, E., Durrant, K. L., Gheita, T. A., Hill, C. L., Howard, R. A., Hoyer, B. F., Hsieh, E., El Kibbi, L., Kilian, A., Kim, A. H., Liew, D. F., Lo, C., Miller, B., Mingolla, S., Nudel, M., Palmerlee, C. A., Singh, J. A., Singh, N., Ugarte-Gil, M. F., Wallace, J., Young, K. J., Bhana, S., Costello, W., Grainger, R., Machado, P. M., Robinson, P. C., Sufka, P., Wallace, Z. S., Yazdany, J., Harrison, C., Larche, M., Levine, M., Foster, G., Thabane, L., Rider, L. G., Hausmann, J. S., Simard, J. F., Sparks, J. A. 2021; 7 (3)

  Abstract

  BACKGROUND: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.METHODS: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.RESULTS: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.CONCLUSION: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.

  View details for DOI 10.1136/rmdopen-2021-001814

  View details for PubMedID 34493645

• The Burden of Systemic Lupus in Five Distinct Racial and Ethnic Groups in Israel: A Population-based Study Falasinnu, T., Rizk, N., Feldman, B., Zisman, D., Leshchinsky, M., Lawrence, G., Chaichian, Y., Simard, J. WILEY. 2021: 1203-1207

  View details for Web of Science ID 000744545202106

• Are we missing lupus in males? Evidence of cognitive bias from a randomized experiment in the US. American journal of epidemiology Simard, J. F., Chaichian, Y., Rizk, N., Rector, A., Feldman, C. H., Falasinnu, T. O. 2021

  View details for DOI 10.1093/aje/kwab199

  View details for PubMedID 34308469

• Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours: results from an international survey of people with rheumatic diseases. The Lancet. Rheumatology Hausmann, J. S., Kennedy, K., Simard, J. F., Liew, J. W., Sparks, J. A., Moni, T. T., Harrison, C., Larche, M. J., Levine, M., Sattui, S. E., Semalulu, T., Foster, G., Surangiwala, S., Thabane, L., Beesley, R. P., Durrant, K. L., Mateus, E. F., Mingolla, S., Nudel, M., Palmerlee, C. A., Richards, D. P., Liew, D. F., Hill, C. L., Bhana, S., Costello, W., Grainger, R., Machado, P. M., Robinson, P. C., Sufka, P., Wallace, Z. S., Yazdany, J., Sirotich, E., COVID-19 Global Rheumatology Alliance, Robinson, P. C., Bhana, S., Liew, J. W., Sufka, P. H., Singh, N., Howard, R. A., Kim, A. H., Westrich-Robertson, T., Sirotich, E., Tsui, E., Duarte-Garcia, A., Sparks, J. A., Tam, H., Jayatilleke, A., Konig, M. F., Graef, E. R., Putman, M. S., Syed, R. H., Korsten, P., Mateus, E., Sattui, S. E., Wallace, Z. S., Laura, U. A., Adam, K., Chock, Y. P., White, D. W., Zamora, G. T., Traboco, L. S., Patel, A. M., Grainger, R., Ugarte-Gil, M. F., Gianfrancesco, M. A., Amigues, I., Sanchez-Alvarez, C., Trupin, L., Jacobsohn, L. R., Beesley, R. P., Hoyer, B. F., Machado, P. M., Makan, K., Gossec, L., Priyank, C., Leipe, J., Wallace, B., Angeles-Han, S. T., Almaghlouth, I. A., Katherine, W. D., Padula, A. S., Berenbaum, F., Treemarcki, E. M., Sinha, R., Lewandowski, L. B., Webb, K., Young, K. J., Bulina, I., Herrera Uribe, S., Rubinstein, T. B., Nolan, M. W., Ang, E. Y., Venuturupalli, S. R., Hausmann, J. S., Dubreuil, M., Pisoni, C. N., Cosatti, M. A., Campos, J., Simard, J. F., Conway, R., Peterson, T. M., Harrison, C. O., Felix, C., Richards, D. P., Proulx, L., Akpabio, A. A., Worthing, A. B., Laidlaw, L. R., Reid, P., Palmerlee, C. A., Danila, M. I., Sahar, L., Linh, N. Q., Agarwal, A., Studenic, P., Liew, D. F., Larche, M. J., Mingolla, S. A., Zamora, E. A., Angevare, S. S., Sinha, R. R., Durrant, K. L., Peirce, A., Somers, E. C., Cappelli, L. C., Frankel, B. A., Kumar, B., Silinsky Krupnikova, S. D., Rosario Vega, J. A., Frankovich, J., Fernandez-Ruiz, R., Posada Velasquez, M., Yeoh, S., Marino, M., Nudel, M., Scott, C., Rodriguez, C., Martin Mancheno, A. I., Seo, P., Gamboa-Cardenas, R. V., Pimentel-Quiroz, V. R., Reategui-Sokolova, C., Kihara, M., Lin, C. M., Kattula, D., Laila, G., Carmona, L., Wallace, J., Yazdany, J., Costello, W., Gore-Massy, M. C., Tomasella, L., Kodek, M. A. 2021

  Abstract

  Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide.Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis.Findings: 12117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjogren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514).Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity.Funding: American College of Rheumatology.

  View details for DOI 10.1016/S2665-9913(21)00175-2

  View details for PubMedID 34316727

• Antimalarial Drug Shortages During the COVID-19 Pandemic: Results From the Global Rheumatology Alliance Patient Experience Survey Sirotich, E., Kennedy, K., Surangiwala, S., Semalulu, T., Larche, M., Liew, J., Wallace, Z., Robinson, P., Grainger, R., Sparks, J., Simard, J., Yazdany, J., Gore-Massy, M., Howard, R., Levine, M., Hausmann, J. J RHEUMATOL PUBL CO. 2021: 1136-1137

  View details for Web of Science ID 000680554800106

• Corrigendum to 'TNF-alpha Inhibition for the Treatment of Cardiac Sarcoidosis' Seminars in Arthritis and Rheumatism. 2020 Jun;50(3):546-552. Seminars in arthritis and rheumatism Baker, M. C., Sheth, K., Witteles, R., Genovese, M. C., Shoor, S., Simard, J. F. 2021

  View details for DOI 10.1016/j.semarthrit.2021.05.009

  View details for PubMedID 34172273

• CORRELATES OF TESTING POSITIVE FOR SARS-COV-2 IN PATIENTS WITH RHEUMATIC AD MUSCULOSKELETAL DISEASES Singh, N., Huang, I., Singleton, M., Bays, A., Sabo, J., Chung, S., Gardner, G., Schaeffer, J., Wysham, K., Andrews, J., Patel, R., Simard, J., Liew, J. BMJ PUBLISHING GROUP. 2021: 994

  View details for DOI 10.1136/annrheumdis-2021-eular.858

  View details for Web of Science ID 000692653200317

• Evidence of under-reporting of early-onset preeclampsia using register data. Paediatric and perinatal epidemiology Simard, J. F., Rossides, M., Wikstrom, A., Falasinnu, T., Palmsten, K., Arkema, E. V. 2021

  Abstract

  BACKGROUND: Early-onset preeclampsia, traditionally defined as presenting before 34 gestational weeks, is associated with even higher risks of perinatal death, placental abruption, and stroke, than late-onset preeclampsia.OBJECTIVE: We estimated the degree of misclassification in a high-risk population of lupus pregnancies and a general population comparator when gestational age at delivery defined preeclampsia phenotype compared to first preeclampsia diagnosis.METHODS: Patients with lupus and general population comparators from Sweden with ≥1 singleton pregnancy in the Medical Birth Register with a documented ICD code for preeclampsia were included (2002-2016). We used gestational age at delivery (<34 versus ≥34weeks) to phenotype preeclampsia early- versus late-onset and then reclassified based on first preeclampsia diagnosis date in the Patient Register. We cross-tabulated the two definitions and calculated sensitivity using the visit-based definition as the reference standard for general population and lupus pregnancies, overall and among nulliparous women.RESULTS: 331 pregnancies were diagnosed with preeclampsia, of which 322 were in both registers. Of those, 58 were early-onset based on gestational age at delivery (n=29 in lupus pregnancies). Overall, 9% of early-onset preeclampsia in lupus (sensitivity 91%, 95% confidence interval [CI] 75, 98) was misclassified as late-onset compared to 19% in the general population (sensitivity 81%, 95% CI 64, 92). We noted similar misclassification (4% vs 22%) among nulliparous women.CONCLUSIONS: In the general population, early-onset preeclampsia was more likely misclassified as late-onset than in the high-risk lupus population. Relying on gestational age at delivery to phenotype preeclampsia, this way underestimates the occurrence of early-onset preeclampsia. This also suggests that the burden of early-onset preeclampsia as a public health concern may be under-reported, although this may be more applicable to milder preeclampsia where expectant management is employed. Research of biological and maternal predictors of early-onset preeclampsia may be dealing with differentially misclassified outcomes or samples.

  View details for DOI 10.1111/ppe.12759

  View details for PubMedID 33956365

• The Impact of the first COVID-19 shelter-in-place announcement on social distancing, difficulty in daily activities, and levels of concern in the San Francisco Bay Area: A cross-sectional social media survey. PloS one Elser, H. n., Kiang, M. V., John, E. M., Simard, J. F., Bondy, M. n., Nelson, L. M., Chen, W. T., Linos, E. n. 2021; 16 (1): e0244819

  Abstract

  The U.S. has experienced an unprecedented number of orders to shelter in place throughout the ongoing COVID-19 pandemic. We aimed to ascertain whether social distancing; difficulty with daily activities; and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of the nation's first shelter-in-place orders (SIPO) among individuals living in the seven affected counties in the San Francisco Bay Area.We conducted an online, cross-sectional social media survey from March 14 -April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area versus elsewhere in the U.S.In this non-representative sample, the percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty obtaining hand sanitizer, medications, and in particular respondents reported increased difficulty obtaining food in the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the announcement.This study characterizes early changes in attitudes, behaviors, and difficulties. As states and localities implement, rollback, and reinstate shelter-in-place orders, ongoing efforts to more fully examine the social, economic, and health impacts of COVID-19, especially among vulnerable populations, are urgently needed.

  View details for DOI 10.1371/journal.pone.0244819

  View details for PubMedID 33444363

• Distinct patterns of comorbidity prior to diagnosis of incident systemic lupus erythematosus in the Danish population. Journal of autoimmunity Hansen, R. B., Simard, J. F., Faurschou, M., Jacobsen, S. 2021; 123: 102692

  Abstract

  The objective of this study was to assess the cumulative prevalence of pre-existing comorbidities among patients diagnosed with systemic lupus erythematosus (SLE) in Denmark. The study included patients aged ≥18 years at the index date set to the date of first registration of SLE in the Danish National Patient Registry (DNPR) between 1996 and 2018. Up to 19 age- and sex-matched general population comparators per case were selected. Comorbidity diagnoses were retrieved from the DNPR based on International Classification of Diseases codes. We estimated cumulative prevalence of various comorbidities among cases and comparators, prevalence differences (PDs), and prevalence ratios (PRs), with PDs and PRs adjusted for age and sex, at the index date and 1, 2, 5, and 10 years before the index date. We identified 3,010 SLE cases and 57,046 comparators (mean age at index date: 47.3 years). Most comorbidities occurred more often in SLE patients versus comparators at the index date and up to 10 years before. Overrepresented comorbidities in SLE patients 10 years before SLE diagnosis included neuropsychiatric, cardiovascular, and venous thromboembolic diseases; PDs (95% CI) were 2.3% (1.4-3.3%), 1.3% (0.6-1.9%), and 1.1% (0.6-1.5%), respectively; corresponding PRs (95% CI) were 1.5 (1.3-1.8), 1.7 (1.4-2.1), and 4.3 (3.1-6.1). We found a higher prevalence of multiple comorbidities-not only at the time of SLE diagnosis but likewise during the 10-year pre-diagnosis period-among individuals with SLE. These findings underscore the importance of early clinical vigilance toward comorbidities starting in the diagnostic phase of SLE.

  View details for DOI 10.1016/j.jaut.2021.102692

  View details for PubMedID 34364172

• Pulse dose steroid experience among hospitalized patients with systemic lupus erythematosus: a single-center feasibility study. Clinical rheumatology Chaichian, Y. n., Weisman, M. H., Simard, J. F. 2021

  Abstract

  Pulse intravenous (IV) methylprednisolone (MEP) is often used for severe SLE manifestations requiring hospitalization. However, the accuracy of pulse dose documentation extracted from the electronic health record (EHR) is unknown. We assessed the feasibility to study pulse steroid dosing among hospitalized patients with SLE at our institution. Using the Stanford Medicine Research Data Repository (STARR) extracted from the EHR, we identified patients with ≥ 1 SLE ICD code before/during hospitalization receiving steroids (1/2008-12/2017). SLE diagnosis required rheumatologist confirmation. For our feasibility study, we randomly sampled 40/747 patients meeting search criteria. Pulse IV MEP was defined as ≥ 200 mg. Pharmacy dispensation data required EHR confirmation. Forty adult and pediatric subjects were identified, passing initial criteria screen; 6 pediatric patients were excluded as EHR pharmacy confirmation was unavailable. Of the 34 adults, 14 had SLE confirmed. Among 5 adult SLE patients with pulse documentation, 3 occurred while hospitalized, for the following indications: acute renal transplant rejection (2 patients, 2 hospitalizations) and lupus flare (1 patient, 2 hospitalizations). No discrepancies were observed in pharmacy dispensation documentation of pulse dosing between EHR and STARR for all 4 hospitalizations.Assessment of pulse steroid dose dispensation among hospitalized patients with SLE can be reliably ascertained from the extracted portion of the EHR designed for research. Reliance on a single ICD code for SLE in the EHR may lead to high rate of false-positive diagnoses of SLE among hospitalized patients. We document the importance of supplementing one ICD code with additional clinical information when confirming SLE diagnosis. Key Points • Assessment of pulse steroid dosing dispensation among hospitalized patients with SLE can be reliably determined from the extracted portion of the EHR designed for research purposes. • Reliance on a single ICD code contributes to a high rate of false positive diagnoses of SLE among hospitalized patients. • Supplementing ICD coding with additional clinical information is vital when confirming SLE diagnosis.

  View details for DOI 10.1007/s10067-021-05644-4

  View details for PubMedID 33608793

• Reproductive sequelae of parental severe illness before the pandemic: implications for the COVID-19 pandemic. Fertility and sterility Kasman, A. M., Bhambhvani, H. P., Li, S., Zhang, C. A., Stevenson, D. K., Shaw, G. M., Simard, J. F., Eisenberg, M. L. 2020; 114 (6): 1242–49

  Abstract

  OBJECTIVE: To investigate, with pre-COVID-19 data, whether parental exposure to severe systemic infections near the time of conception is associated with pregnancy outcomes.DESIGN: Retrospective cohort study.SETTING: Population-based study covering births within the United States from 2009 to2016.PARTICIPANTS: The IBM MarketScan Research database covers reimbursed health care claims data on inpatient and outpatient encounters that are privately insured through employment-sponsored health insurance. Our analytic sample included pregnancies to paired fathers and mothers.INTERVENTIONS(S): Parental preconception exposure (0-6 months before conception) to severe systemic infection (e.g., sepsis, hypotension, respiratory failure, critical care evaluation).MAIN OUTCOME MEASURE(S): Preterm birth (i.e., live birth before 37 weeks) and pregnancy loss.RESULT(S): A total of 999,866 pregnancies were recorded with 214,057 pregnancy losses (21.4%) and 51,759 preterm births (5.2%). Mothers receiving intensive care in the preconception period had increased risk of pregnancy loss, as did fathers. Mothers with preconception sepsis had higher risk of preterm birth and pregnancy loss, and paternal sepsis exposure was associated with an increased risk of pregnancy loss. Similar results were noted for hypotension. In addition, a dose response was observed for both mothers and fathers between preconception time in intensive care and the risk of preterm birth and pregnancy loss.CONCLUSION(S): In a pre-COVID-19 cohort, parental preconception severe systemic infection was associated with increased odds of preterm birth and pregnancy loss when conception was soon after the illness.

  View details for DOI 10.1016/j.fertnstert.2020.09.153

  View details for PubMedID 33280730

• Systemic lupus erythematosus during pregnancy is not associated with school performance in offspring - A Danish population-based study. Lupus Knudsen, S. S., Simard, J. F., Knudsen, J. S., Christensen, J., Laursen, T. M., Deleuran, B. W., Bech, B. H. 2020: 961203320973076

  Abstract

  INTRODUCTION: Systemic lupus erythematosus (SLE) in pregnancy is considered a risk factor for a range of adverse outcomes in the offspring. Studies have indicated increased risk of neurodevelopmental disorders such as autism spectrum disorders, dyslexia and ADHD. However, the overall long-term cognitive development of children born to women with SLE has scarcely been examined. In this study, we compare test scores from the Danish National School Tests of children born to women SLE with children of the background population.METHODS: We included all singleton children born in Denmark between 1995 and 2008, who were listed in the Danish National School Test Register (n=738,862). Children born to women with SLE were identified through linkage of national healthcare registers. We assessed the children's performance in the national school tests between 2nd and 8th grade, in reading and mathematics. Information on the mothers' redeemed prescriptions in pregnancy was included in stratified analyses. Differences of mean test scores were derived from linear regressions and compared according to maternal SLE status, and predefined categories of medication exposures.RESULTS: In total, 312 (0.04%) children were born to mothers with SLE. There were no differences in performance in neither reading nor mathematics tests between those born to mothers with SLE and children born to mothers without SLE. When stratifying on medication exposures among children whose mothers had SLE, there was a non-significant tendency towards poorer results among those exposed to hydroxychloroquine and/or immunosuppressants (n=31), compared to those not exposed to these medications. A similar tendency was not observed among children whose mothers received hydroxychloroquine for non-SLE reasons (n=1,235).CONCLUSION: This study indicates no major harmful effect on the child's neurocognitive development from exposure in utero to SLE, hydroxychloroquine and/or immunosuppressants, as measured by school performance.

  View details for DOI 10.1177/0961203320973076

  View details for PubMedID 33197369

• Increasing Ancestral Diversity in Lupus Trials: Ways Forward. Rheumatic diseases clinics of North America Falasinnu, T., Chaichian, Y., Simard, J. F. 2020; 46 (4): 713–22

  Abstract

  Significant disparities exist in systemic lupus erythematosus (SLE) regarding prevalence, disease severity, and mortality, with race/ethnic minorities being disproportionately affected in the United States. This review highlights that despite these disparities, race/ethnic minority underrepresentation remains an issue within SLE research. Decreased race/ethnic minority involvement in SLE research has real-world implications, including less understanding of the disease and less applicability of approved therapies among diverse groups of patients. Members of the SLE research community have an obligation to narrow this gap to ensure that future advances within the field are derived from and benefit a more representative group of patients.

  View details for DOI 10.1016/j.rdc.2020.07.011

  View details for PubMedID 32981648

• Increased Rates of Obstetric Complications Prior to Systemic Sclerosis Diagnosis Chung, M., Kolstad, K., Dontsi, M., Manwani, P., Zhao, H., Postlethwaite, D., Kesh, S., Simard, J., Chung, L. WILEY. 2020

  View details for Web of Science ID 000587568500383

• Antimalarial Drug Shortages During the COVID-19 Pandemic: Results from the Global Rheumatology Alliance Patient Experience Survey Sirotich, E., Kennedy, K., Surangiwala, S., Semalulu, T., Larche, M., Liew, J., Wallace, Z., Robinson, P., Grainger, R., Sparks, J., Simard, J., Yazdany, J., Gore-Massy, M., Howard, R., Levine, M., Hausmann, J. WILEY. 2020

  View details for Web of Science ID 000587568500008

• Prevalence of Morbidity Prior to Diagnosis of Incident Systemic Lupus Erythematosus in the Danish Population Simard, J., Faurschou, M., Jacobsen, S., Hansen, R. WILEY. 2020

  View details for Web of Science ID 000587568504042

• Prevalence of a Diagnosis of Osteopenia/Osteoporosis Amongst Patients with Systemic Sclerosis and Identification of Associated Clinical Factors Wang, G., Mar, D., Wu, J., Simard, J., Popat, R., Chung, L. WILEY. 2020

  View details for Web of Science ID 000587568500395

• Insights From Twitter Conversations on Lupus and Reproductive Health: Protocol for a Content Analysis. JMIR research protocols Stens, O., Weisman, M. H., Simard, J., Reuter, K. 2020; 9 (8): e15623

  Abstract

  BACKGROUND: Systemic lupus erythematosus (SLE) is the most common form of lupus. It is a chronic autoimmune disease that predominantly affects women of reproductive age, impacting contraception, fertility, and pregnancy. Although clinic-based studies have contributed to an increased understanding of reproductive health care needs of patients with SLE, misinformation abounds and perspectives on reproductive health issues among patients with lupus remain poorly understood. Social networks such as Twitter may serve as a data source for exploring how lupus patients communicate about their health issues, thus adding a dimension to enrich our understanding of communication regarding reproductive health in this unique patient population.OBJECTIVE: The objective of this study is to conduct a content analysis of Twitter data published by users in English in the United States from September 1, 2017, to October 31, 2018, in order to examine people's perspectives on reproductive health among patients with lupus.METHODS: This study will analyze user-generated posts that include keywords related to lupus and reproductive health from Twitter. To access public Twitter user data, we will use Symplur Signals, a health care social media analytics platform. Text classifiers will be used to identify topics in posts. Posts will be classified manually into the a priori and emergent categories. Based on the information available in a user's Twitter profile (ie, username, description, and profile image), we will further attempt to characterize the user who generated the post. We will use descriptive statistics to analyze the data and identify the most prevalent topics in the Twitter content among patients with lupus.RESULTS: This study has been funded by the National Center for Advancing Translational Science (NCATS) through their Clinical and Translational Science Awards program. The Institutional Review Board at the University of Southern California approved the study (HS-18-00912). Data extraction and cleaning are complete. We obtained 47,715 Twitter posts containing terms related to "lupus" from users in the United States, published in English between September 1, 2017, and October 31, 2018. We will include 40,885 posts in the analysis, which will be completed in fall 2020. This study was supported by funds from the has been funded by the National Center for Advancing Translational Science (NCATS) through their Clinical and Translational Science Awards program.CONCLUSIONS: The findings from this study will provide pilot data on the use of Twitter among patients with lupus. Our findings will shed light on whether Twitter is a promising data source for learning about reproductive health issues expressed among patients with lupus. The data will also help to determine whether Twitter can serve as a potential outreach platform for raising awareness of lupus and reproductive health and for implementing relevant health interventions.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15623.

  View details for DOI 10.2196/15623

  View details for PubMedID 32844753

• Response to: 'Glucocorticoid-induced relapse of COVID-19 in a patient with sarcoidosis' by Gyorfi et al. Annals of the rheumatic diseases Gianfrancesco, M., Hyrich, K. L., Yazdany, J., Machado, P. M., Robinson, P. C. 2020

  View details for DOI 10.1136/annrheumdis-2020-218328

  View details for PubMedID 32606045

• Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry. Annals of the rheumatic diseases Gianfrancesco, M., Hyrich, K. L., Al-Adely, S., Carmona, L., Danila, M. I., Gossec, L., Izadi, Z., Jacobsohn, L., Katz, P., Lawson-Tovey, S., Mateus, E. F., Rush, S., Schmajuk, G., Simard, J., Strangfeld, A., Trupin, L., Wysham, K. D., Bhana, S., Costello, W., Grainger, R., Hausmann, J. S., Liew, J. W., Sirotich, E., Sufka, P., Wallace, Z. S., Yazdany, J., Machado, P. M., Robinson, P. C., COVID-19 Global Rheumatology Alliance 2020

  Abstract

  OBJECTIVES: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease.METHODS: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed.RESULTS: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10mg/day was associated with higher odds of hospitalisation (OR 2.05, 95%CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95%CI 0.70 to 2.17 and OR 0.74, 95%CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95%CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95%CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95%CI 0.57 to 1.57) was observed.CONCLUSIONS: We found that glucocorticoid exposure of ≥10mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.

  View details for DOI 10.1136/annrheumdis-2020-217871

  View details for PubMedID 32471903

• Rheumatoid arthritis in pregnancy and school performance in offspring. Arthritis care & research Knudsen, S. S., Simard, J. F., Christensen, J., Laursen, T. M., Deleuran, B. W., Bech, B. H. 2020

  Abstract

  OBJECTIVES: To examine the overall cognitive development of children exposed to maternal rheumatoid arthritis (RA) in utero by comparing their school test scores, to those of their peers.METHODS: Children born in Denmark 1995-2008, and listed in the National School Test Register were included (n=738,862). Children exposed to maternal RA were identified through linkage of national registers. In separate analyses, exposure was subdivided according to maternal serostatus. Preclinical maternal RA was included as a separate exposure. The Danish National School Tests are mandatory, standardized tests. Results from all reading tests (grades 2, 4, 6 and 8) and mathematics tests (grades 3 and 6) from 2010-2017 were included. Test scores were compared according to maternal RA exposure, for each test separately, using linear regressions.RESULTS: we identified 934 children exposed to maternal RA in utero. There were no differences in reading test scores, between maternal RA exposed and unexposed children. RA exposed children scored poorer in both mathematics tests (adjusted differences of mean score: -0.14 standard deviations (SD) (95% CI: -0.23; -0.06 ) and -0.16 SD (95% CI: -0.26 -0.07 ). There was no appreciable difference between children by maternal RA serostatus. Children exposed to preclinical RA (n=589) showed the same pattern of performance as children exposed to RA.CONCLUSIONS: RA exposed children scored slightly poorer in mathematics tests, but performed as well as their unexposed peers in the reading tests. The results do not suggest that RA in pregnancy has a major impact on offspring school performance.

  View details for DOI 10.1002/acr.24223

  View details for PubMedID 32339372

• Festina lente: hydroxychloroquine, covid-19 and the role of the rheumatologist. Annals of the rheumatic diseases Graef, E. R., Liew, J. W., Putman, M. S., Simard, J. F., Sirotich, E., Berenbaum, F., Duarte-Garcia, A., Grainger, R., Harrison, C., Konig, M. F., Korsten, P., Proulx, L., Richards, D. P., Robinson, P. C., Sattui, S. E., Ugarte-Gil, M. F., Young, K. J., Kim, A. H., Sparks, J. A., COVID-19 Global Rheumatology Alliance 2020

  View details for DOI 10.1136/annrheumdis-2020-217480

  View details for PubMedID 32295786

• Increased Mortality in Asians With Systemic Sclerosis in Northern California. ACR open rheumatology Chung, M. P., Dontsi, M., Postlethwaite, D., Kesh, S., Simard, J. F., Fiorentino, D., Zaba, L. C., Chung, L. 2020

  Abstract

  OBJECTIVE: The objective of this study is to evaluate racial/ethnic differences in disease manifestations and survival in a US cohort of patients with systemic sclerosis (SSc), with a focus on Asian patients.METHODS: A retrospective cohort study was conducted among Kaiser Permanente Northern California adults with an incident SSc diagnosis by a rheumatologist from 2007 to 2016, confirmed by a chart review to fulfill 2013 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. Self-reported race/ethnicity was categorized as non-Hispanic white, Asian, Hispanic, and black. Disease manifestations and survival were compared, using white patients as the reference.RESULTS: A total of 609 patients with incident SSc were identified: 89% were women, and 81% had limited cutaneous SSc, with a mean age at diagnosis of 55.4 ± 14.8 years. The racial/ethnic distribution was 51% non-Hispanic white (n = 310), 25% Hispanic (n = 154), 16% Asian (n = 96), and 8% black (n = 49). Compared with white patients, black patients had a greater prevalence of diffuse disease (14.5% vs. 44.9%; P < 0.001), and Asians had higher rates of anti-U1-RNP antibodies (32.1% vs. 11.9%; P = 0.005). Nine-year overall survival rates following SSc diagnosis were lower in Asian (52.3%), black (52.2%), and Hispanic patients (68.2%) compared with white patients (75.8%). Pulmonary hypertension and infections were the leading causes of death in Asian patients. Asian race was associated with higher mortality on univariable (hazard ratio [HR] 1.83 [95% confidence interval (CI) 1.08-2.99]; P = 0.020) and multivariable analyses (HR 1.80 [95% CI 0.99-3.16]; P = 0.047) when adjusting for age, sex, body mass index, cutaneous subtype, smoking status, interstitial lung disease, pulmonary hypertension, renal crisis, and malabsorption syndrome.CONCLUSION: Asian patients with SSc in this US cohort had increased mortality compared with white patients. These patients warrant close monitoring for disease progression.

  View details for DOI 10.1002/acr2.11126

  View details for PubMedID 32198914

• 2019 American College of Rheumatology Reproductive Health in Rheumatic and Musculoskeletal Diseases Guideline. Arthritis care & research Sammaritano, L. R., Bermas, B. L., Chakravarty, E. E., Chambers, C., Clowse, M. E., Lockshin, M. D., Marder, W., Guyatt, G., Ware Branch, D., Buyon, J., Christopher-Stine, L., Crow-Hercher, R., Cush, J., Druzin, M., Kavanaugh, A., Laskin, C. A., Plante, L., Salmon, J., Simard, J., Somers, E. C., Steen, V., Tedeschi, S. K., Vinet, E., Whitney White, C., Yazdany, J., Barbhaiya, M., Bettendorf, B., Eudy, A., Jayatilleke, A., Aakash Shah, A., Sullivan, N., Tarter, L. L., Birru Talabi, M., Turgunbaev, M., Turner, A., D'Anci, K. E. 2020

  Abstract

  OBJECTIVE: To develop an evidence-based guideline for rheumatic and musculoskeletal disease (RMD) patients regarding contraception; assisted reproductive technology (ART); fertility preservation; pregnancy assessment, counseling, and management; medication use before, during and after pregnancy; and hormone replacement therapy (HRT).METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, pregnancy and lactation, and HRT in RMD populations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence, and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements (GPS) were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.RESULTS: This ACR guideline provides 12 ungraded GPS and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus (SLE), those positive for antiphospholipid antibody (aPL) and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and GPS support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while on pregnancy compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues given the overall low level of evidence available for RMD patients in this area.CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences and comorbidities.

  View details for DOI 10.1002/acr.24130

  View details for PubMedID 32090466

• 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis & rheumatology (Hoboken, N.J.) Sammaritano, L. R., Bermas, B. L., Chakravarty, E. E., Chambers, C., Clowse, M. E., Lockshin, M. D., Marder, W., Guyatt, G., Branch, D. W., Buyon, J., Christopher-Stine, L., Crow-Hercher, R., Cush, J., Druzin, M., Kavanaugh, A., Laskin, C. A., Plante, L., Salmon, J., Simard, J., Somers, E. C., Steen, V., Tedeschi, S. K., Vinet, E., White, C. W., Yazdany, J., Barbhaiya, M., Bettendorf, B., Eudy, A., Jayatilleke, A., Shah, A. A., Sullivan, N., Tarter, L. L., Birru Talabi, M., Turgunbaev, M., Turner, A., D'Anci, K. E. 2020

  Abstract

  OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD.CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

  View details for DOI 10.1002/art.41191

  View details for PubMedID 32090480

• Maternal hypertensive disorders in SLE pregnancy and future cardiovascular outcomes. Arthritis care & research Simard, J. F., Rossides, M., Arkema, E. V., Svenungsson, E., Wikstrom, A., Mittleman, M. A., Salmon, J. E. 2020

  Abstract

  BACKGROUND: Hypertensive disorders of pregnancy (HDP) increase cardiovascular disease (CVD) risk. Pregnancy morbidities, including preeclampsia, and CVD are common in systemic lupus erythematosus (SLE). Possible connections are important to explore. In a population-based cohort, we investigated whether HDP is associated with a higher risk of cardiovascular outcomes separately in SLE and non-SLE to examine the role of SLE.METHODS: We identified first singleton births in the Medical Birth Register (1987-2012) among mothers with SLE and a large general population comparison group. Discharge diagnoses for HDP, cardiovascular outcomes, and hypertension in the Patient Register were identified using ICD codes. We estimated adjusted hazard ratios and 95% confidence intervals (HR, 95% CI) of the association between HDP and outcomes, in separate models in women with and without SLE. We then evaluated additive and multiplicative effect modification using relative excess risk due to interaction and Cox models jointly accounting for SLE and HDP, respectively. Mediation analysis estimated the proportion of the association between SLE and outcome explained by HDP.RESULTS: HDP were more common in SLE pregnancies (20% vs 7%). In SLE, HDP were associated with a two-fold higher rate of cardiovascular outcomes and three-fold higher rate of incident hypertension. HDP mediated 20% of the latter association. In women without SLE, HDP was associated with higher hypertension incidence later in life.CONCLUSION: In women with and without SLE, HDP were associated with a three-fold higher rate of hypertension. In SLE, women with HDP developed cardiovascular outcomes twice as often as women without HDP.

  View details for DOI 10.1002/acr.24160

  View details for PubMedID 32004410

• Does Hydroxychloroquine Protect against Preeclampsia and Preterm Delivery in Systemic Lupus Erythematosus Pregnancies? American journal of perinatology Do, S. C., Rizk, N. M., Druzin, M. L., Simard, J. F. 2020

  Abstract

   Systemic lupus erythematosus (SLE) increases the risk of complications in pregnancy. Hydroxychloroquine (HCQ) decreases flares and neonatal lupus syndrome. Limited evidence suggests that HCQ also reduces preeclampsia and preterm birth in SLE pregnancies. We studied whether HCQ was associated with lower odds of preeclampsia and preterm delivery in SLE pregnancies. We conducted a retrospective cohort study of 129 deliveries of 110 patients with SLE delivered at a single institution (2000-2017). HCQ exposure and preeclampsia, along with other clinical data, were extracted from chart review. Crude and multivariable-adjusted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). A total of 41% were exposed to HCQ, of whom 13.5% were complicated by preeclampsia versus 26.3% unexposed to HCQ (adjusted OR = 0.5; 95% CI: 0.2-1.4). The difference was pronounced for first pregnancies (7 vs. 44%), but power was limited. The difference in preterm deliveries was less pronounced comparing HCQ-exposed pregnancies with HCQ-unexposed pregnancies (34 vs. 40.8%; OR = 0.3; 95% CI: 0.3-1.5). Pregnant SLE patients trended toward less preeclampsia and preterm delivery when treated with HCQ. Future larger studies are needed to increase the statistical power, account for additional potential confounders, and more fully account for parity.

  View details for DOI 10.1055/s-0039-3402752

  View details for PubMedID 31899930

• Inflammatory Bowel Disease in Children with Systemic Juvenile Idiopathic Arthritis. The Journal of rheumatology Maller, J. n., Fox, E. n., Park, K. T., Paul, S. S., Baszis, K. n., Borocco, C. n., Prahalad, S. n., Quartier, P. n., Reinhardt, A. n., Schonenberg-Meinema, D. n., Shipman, L. n., Terreri, M. T., Simard, J. n., Lavi, I. n., Chalom, E. n., Hsu, J. n., Zisman, D. n., Mellins, E. D. 2020

  Abstract

  The incidence of inflammatory bowel disease (IBD) in juvenile idiopathic arthritis (JIA) is higher than in the general pediatric population. However, reports of IBD in the systemic JIA (sJIA) subtype are limited. We sought to characterize sJIA patients diagnosed with IBD and to identify potential contributing risk factors.Using an internationally distributed survey, we identified 16 sJIA patients who were subsequently diagnosed with IBD (sJIA-IBD cohort). 522 sJIA patients without IBD were identified from the CARRA Legacy Registry and served as the sJIA-only cohort for comparison. Differences in demographic, clinical characteristics and therapy were assessed using chi-square test, Fisher's exact test, t-test, and univariate and multivariate logistic regression as appropriate.75% of sJIA-IBD patients had a persistent sJIA course; 25% had a history of MAS. sJIAIBD subjects were older at sJIA diagnosis, more often non-White, had a higher rate of IBD family history, and were more frequently treated with etanercept or canakinumab compared to sJIA-only subjects. 69% of sJIA-IBD patients successfully discontinued sJIA medications following IBD diagnosis, and sJIA symptoms resolved in 9/12 patients treated with TNF-α inhibitors.IBD in the setting of sJIA is a rare occurrence. The favorable response of sJIA symptoms to therapeutic TNF-α inhibition suggests that the sJIA-IBD cohort may represent a mechanistically distinct sJIA subgroup. Our study highlights the importance of maintaining a high level of suspicion for IBD when gastrointestinal involvement occurs in sJIA patients and the likely broad benefit of TNF-α inhibition in those cases.

  View details for DOI 10.3899/jrheum.200230

  View details for PubMedID 32541073

• US Public Concerns About the COVID-19 Pandemic From Results of a Survey Given via Social Media. JAMA internal medicine Nelson, L. M., Simard, J. F., Oluyomi, A. n., Nava, V. n., Rosas, L. G., Bondy, M. n., Linos, E. n. 2020

  View details for DOI 10.1001/jamainternmed.2020.1369

  View details for PubMedID 32259192

• Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19. Annals of the rheumatic diseases Konig, M. F., Kim, A. H., Scheetz, M. H., Graef, E. R., Liew, J. W., Simard, J. n., Machado, P. M., Gianfrancesco, M. n., Yazdany, J. n., Langguth, D. n., Robinson, P. C. 2020

  View details for DOI 10.1136/annrheumdis-2020-217690

  View details for PubMedID 32381561

• Implications of the COVID-19 San Francisco Bay Area Shelter-in-Place Announcement: A Cross-Sectional Social Media Survey. medRxiv : the preprint server for health sciences Elser, H. n., Kiang, M. V., John, E. M., Simard, J. F., Bondy, M. n., Nelson, L. M., Chen, W. T., Linos, E. n. 2020

  Abstract

  The U.S. has experienced an unprecedented number of shelter-in-place orders throughout the COVID-19 pandemic. There is limited empirical research that examines the impact of these orders. We aimed to rapidly ascertain whether social distancing; difficulty with daily activities (obtaining food, essential medications and childcare); and levels of concern regarding COVID-19 changed after the March 16, 2020 announcement of shelter-in-place orders for seven counties in the San Francisco Bay Area.We conducted an online, cross-sectional social media survey from March 14 - April 1, 2020. We measured changes in social distancing behavior; experienced difficulties with daily activities (i.e., access to healthcare, childcare, obtaining essential food and medications); and level of concern regarding COVID-19 after the March 16 shelter-in-place announcement in the San Francisco Bay Area and elsewhere in the U.S.The percentage of respondents social distancing all of the time increased following the shelter-in-place announcement in the Bay Area (9.2%, 95% CI: 6.6, 11.9) and elsewhere in the U.S. (3.4%, 95% CI: 2.0, 5.0). Respondents also reported increased difficulty with obtaining food, hand sanitizer, and medications, particularly with obtaining food for both respondents from the Bay Area (13.3%, 95% CI: 10.4, 16.3) and elsewhere (8.2%, 95% CI: 6.6, 9.7). We found limited evidence that level of concern regarding the COVID-19 crisis changed following the shelter-in-place announcement.These results capture early changes in attitudes, behaviors, and difficulties. Further research that specifically examines social, economic, and health impacts of COVID-19, especially among vulnerable populations, is urgently needed. =.

  View details for DOI 10.1101/2020.06.29.20143156

  View details for PubMedID 32637974

  View details for PubMedCentralID PMC7340200

• Association of Insulin Resistance With Depression Severity and Remission Status: Defining a Metabolic Endophenotype of Depression. JAMA psychiatry Watson, K. T., Simard, J. F., Henderson, V. W., Nutkiewicz, L. n., Lamers, F. n., Rasgon, N. n., Penninx, B. n. 2020

  View details for DOI 10.1001/jamapsychiatry.2020.3669

  View details for PubMedID 33263725

• Increased Rates of Obstetric Complications Prior to Systemic Sclerosis Diagnosis. Arthritis care & research Chung, M. P., Kolstad, K. D., Dontsi, M. n., Postlethwaite, D. n., Manwani, P. n., Zhao, H. n., Kesh, S. n., Simard, J. F., Chung, L. n. 2020

  Abstract

  To investigate whether obstetric complications prior to systemic sclerosis (SSc) diagnosis are more common compared to the general obstetric population.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 2007-2016. 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 for the outcome SSc.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). SSc cases 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% vs. 50%), including hypertensive disorders (17.7% vs. 9.4%), PROM (11.8% vs. 4.1%), IUGR (5.9% vs 1.8%), maternal infection (29.4% vs. 14.1%), NICU admissions (23.5% vs. 7.7%), and preterm delivery (29.4% vs. 21.8%). Cases had a higher odds of delivering infants requiring NICU admission (OR=4.7, 95% CI 1.2-18.8).Women who eventually develop SSc had trends towards more complicated pregnancy histories before overt diagnosis.

  View details for DOI 10.1002/acr.24533

  View details for PubMedID 33290624

• Toward the Estimation of Unbiased Disease Prevalence Estimates Using Administrative Health Records. The Journal of rheumatology Falasinnu, T., Simard, J. F. 2019; 46 (12): 1549–51

  View details for DOI 10.3899/jrheum.190484

  View details for PubMedID 31787592

• A review of non-immune mediated kidney disease in systemic lupus erythematosus: A hypothetical model of putative risk factors. Seminars in arthritis and rheumatism Falasinnu, T., O'Shaughnessy, M. M., Troxell, M. L., Charu, V., Weisman, M. H., Simard, J. F. 2019

  Abstract

  About half of patients with systemic lupus erythematosus (SLE) are diagnosed with lupus nephritis (LN). Patients with SLE are also at increased risk for diabetes, hypertension and obesity, which together account for >70% of end-stage renal disease in the general population. The frequencies of non-LN related causes of kidney disease, and their contribution to kidney disease development and progression among patients with SLE have been inadequately studied. We hypothesize that a substantial, and increasing proportion of kidney pathology in patients with SLE might not directly relate to LN but instead might be explained by non-immune mediated factors such as diabetes, hypertension, and obesity. The goal of the manuscript is to draw attention to hypertension, diabetes and obesity as potential alternative causes of kidney damage in patients with SLE. Further, we suggest that misclassification of kidney disease etiology in patients with SLE might have important ramifications for clinical trial recruitment, epidemiologic investigation, and clinical care. Future studies aiming to elucidate and distinguish discrete causes of kidney disease - both clinically and histologically - among patients with SLE are desperately needed as improved understanding of disease mechanisms is paramount to advancing therapeutic discovery. Collaboration among rheumatologists, pathologists, nephrologists, and endocrinologists, and the availability of dedicated research funding, will be critical to the success of such efforts.

  View details for DOI 10.1016/j.semarthrit.2019.10.006

  View details for PubMedID 31866044

• Does SLE widen or narrow race/ethnic disparities in the risk of five co-morbid conditions? Evidence from a community-based outpatient care system. Lupus Falasinnu, T., Chaichian, Y., Li, J., Chung, S., Waitzfelder, B. E., Fortmann, S. P., Palaniappan, L., Simard, J. F. 2019: 961203319884646

  Abstract

  OBJECTIVE: The heterogeneous spectrum of systemic lupus erythematosus (SLE) often presents with secondary complications such as cardiovascular disease (CVD), infections and neoplasms. Our study assessed whether the presence of SLE independently increases or reduces the disparities, accounting for the already higher risk of these outcomes among racial/ethnic minority groups without SLE.METHODS: We defined a cohort using electronic health records data (2005-2016) from a mixed-payer community-based outpatient setting in California serving patients of diverse racial/ethnic backgrounds. The eligible population included adult patients with SLE and matched non-SLE patients (≥18 years old). SLE was the primary exposure. The following outcomes were identified: pneumonia, other infections, CVD and neoplasms. For each racial/ethnic group, we calculated the proportion of incident co-morbidities by SLE exposure, followed by logistic regression for each outcome with SLE as the exposure. We evaluated interaction on the additive and multiplicative scales by calculating the relative excess risk due to interaction and estimating the cross-product term in each model.RESULTS: We identified 1036 SLE cases and 8875 controls. The incidence for all outcomes was higher among the SLE exposed. We found little difference in the odds of the outcomes associated with SLE across racial/ethnic groups, even after multivariable adjustment. This finding was consistent on the multiplicative and additive scales.CONCLUSION: We demonstrated that SLE status does not independently confer substantial interaction or heterogeneity by race/ethnicity toward the risk of pneumonia, other infections, CVD or neoplasms. Further studies in larger datasets are necessary to validate this novel finding.

  View details for DOI 10.1177/0961203319884646

  View details for PubMedID 31660790

• Impact of Diabetes on Risk of End Stage Renal Disease in Danish Nationwide Cohort of Newly Diagnosed Patients with Systemic Lupus Erythematosus Hansen, R., Simard, J., Faurschou, M., Jacobsen, S., Falasinnu, T. WILEY. 2019

  View details for Web of Science ID 000507466902437

• Novel Approach to the Treatment of Cardiac Sarcoidosis with TNF-alpha Inhibition Baker, M., Sheth, K., Simard, J., Shoor, S., Genovese, M. WILEY. 2019

  View details for Web of Science ID 000507466900378

• Development of Comorbidity in Danish Nationwide Cohort of Newly Diagnosed Patients with Systemic Lupus Erythematosus Hansen, R., Falasinnu, T., Simard, J., Faurschou, M., Jacobsen, S. WILEY. 2019

  View details for Web of Science ID 000507466902436

• Heritability and Familial Risk of Systemic Lupus Erythematosus in Sweden: A Population-based Case-control Study Arkema, E., Rossides, M., Sjowall, C., Svenungsson, E., Simard, J. WILEY. 2019

  View details for Web of Science ID 000507466901527

• Preterm birth phenotypes in women with autoimmune rheumatic diseases: A population based cohort study. BJOG : an international journal of obstetrics and gynaecology Kolstad, K. D., Mayo, J. A., Chung, L., Chaichian, Y., Kelly, V. M., Druzin, M., Stevenson, D. K., Shaw, G. M., Simard, J. F. 2019

  Abstract

  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 analyzed. Patients with autoimmune disease at delivery were identified by ICD-9 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=2,272, RA n=1,501, SSc n=88, JIA n=187, DM/PM n=38). Multivariable Poisson regression models estimated risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared to the general obstetric population adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care.MAIN OUTCOME MEASURES: PTB was assessed overall (20-36 weeks) and by subphenotype: pre-term premature rupture of membranes (PPROM), spontaneous, or medically indicated PTB. Risk of PTB overall and each phenotype was partitioned by gestational age: early (20-31 weeks) and late (32-36 weeks).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 counseling and close monitoring during pregnancy is crucial.

  View details for DOI 10.1111/1471-0528.15970

  View details for PubMedID 31571337

• High Prevalence of Peripartum Depression Among Physician Mothers: A Cross-Sectional Study. The American journal of psychiatry Choo, E. K., Girgis, C., Han, C. S., Simard, J. F., Adesoye, T., Linos, E., Mangurian, C., Physician Moms Group Study Group 2019; 176 (9): 763–64

  View details for DOI 10.1176/appi.ajp.2019.18121350

  View details for PubMedID 31474130

• Preterm Delivery Phenotypes in Systemic Lupus Erythematosus Pregnancies AMERICAN JOURNAL OF PERINATOLOGY Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. L. 2019; 36 (9): 964–68

  View details for DOI 10.1055/s-0038-1675648

  View details for Web of Science ID 000477661000014

• Knowledge, Motivations, and Practices Regarding Indoor Tanning Among Men Who Have Sex With Men in the San Francisco Bay Area JAMA DERMATOLOGY Morrison, L., Raymond, H. F., Katz, K. A., Simard, J., Admassu, N., Pascua, N., Linos, E. 2019; 155 (7): 852–54

  View details for DOI 10.1001/jamadermatol.2019.0121

  View details for Web of Science ID 000482127300018

• Distinct phenotype of CD4(+) T cells driving celiac disease identified in multiple autoimmune conditions NATURE MEDICINE Christophersen, A., Lund, E. G., Snir, O., Sola, E., Kanduri, C., Dahal-Koirala, S., Zuhlke, S., Molberg, O., Utz, P. J., Rohani-Pichavant, M., Simard, J. F., Dekker, C. L., Lundin, K. A., Sollid, L. M., Davis, M. M. 2019; 25 (5): 734-+

  View details for DOI 10.1038/s41591-019-0403-9

  View details for Web of Science ID 000468247800015

• Indoor tanning among MSM in San Francisco Morrison, L., Raymond, H. F., Katz, K., Simard, J., Admassu, N., Pascua, N., Linos, E. ELSEVIER SCIENCE INC. 2019: S38

  View details for Web of Science ID 000465561502221

• Distinct phenotype of CD4+ T cells driving celiac disease identified in multiple autoimmune conditions. Nature medicine Christophersen, A., Lund, E. G., Snir, O., Sola, E., Kanduri, C., Dahal-Koirala, S., Zuhlke, S., Molberg, O., Utz, P. J., Rohani-Pichavant, M., Simard, J. F., Dekker, C. L., Lundin, K. E., Sollid, L. M., Davis, M. M. 2019

  Abstract

  Combining HLA-DQ-gluten tetramers with mass cytometry and RNA sequencing analysis, we find that gluten-specific CD4+ T cells in the blood and intestines of patients with celiac disease display a surprisingly rare phenotype. Cells with this phenotype are also elevated in patients with systemic sclerosis and systemic lupus erythematosus, suggesting a way to characterize CD4+ T cells specific for disease-driving antigens in multiple autoimmune conditions.

  View details for PubMedID 30911136

• New-onset non-infectious pulmonary manifestations among patients with systemic lupus erythematosus in Sweden. Arthritis research & therapy Forbess, L. J., Rossides, M., Weisman, M. H., Simard, J. F. 2019; 21 (1): 48

  Abstract

  OBJECTIVE: The objective was to estimate the incidence of lung disease among patients with systemic lupus erythematosus (SLE).METHODS: Using Swedish register data, we identified patients with SLE and pulmonary diagnoses from the National Patient Register through ICD codes. We matched patients with SLE with individuals from the general population. Patients with SLE with a history of pulmonary disease were excluded. Incidence rates (IR) and 95% confidence intervals (CI) were calculated overall and by type of pulmonary disease for incident (2003-2013) and prevalent SLE separately. Hazard ratios (HR) and 95% CI of the association between SLE and pulmonary disease were estimated using adjusted Cox regression models. Sensitivity analyses using a semi-automated approach to quantitative probabilistic bias analysis accounted for potential bias due to unmeasured confounding by smoking.RESULTS: There were 3209 incident and 6908 prevalent cases of SLE identified. The IRs for pulmonary disease were similar in prevalent and incident SLE (14 cases per 1000 person-years). Patients with incident SLE had a nearly sixfold higher rate of pulmonary disease compared to the non-SLE population (HR 5.8 (95% CI 4.8-7.0)). Incident and prevalent SLE was associated with an increased rate of interstitial lung disease (HR 19.0 (95% CI 10.7-34.0) and 14.3 (95% CI 10.8-18.8), respectively). Bias due to unmeasured confounding by smoking was unlikely to explain our findings.CONCLUSION: Lung disease is relatively common in patients with SLE compared to the general population. Clinicians caring for patients with SLE should have heightened suspicion of lung disease, including interstitial lung disease, even early within the disease course or at the time of diagnosis of SLE.

  View details for DOI 10.1186/s13075-018-1804-8

  View details for PubMedID 30728079

• Unraveling Race, Socioeconomic Factors, and Geographical Context in the Heterogeneity of Lupus Mortality in the United States. ACR open rheumatology Falasinnu, T. n., Chaichian, Y. n., Palaniappan, L. n., Simard, J. F. 2019; 1 (3): 164–72

  Abstract

  Systemic lupus erythematosus (SLE) is a chronic autoimmune disease disproportionately affecting women and racial/ethnic minorities. We examined SLE-related mortality over time to assess whether the impact of race is attenuated when social economic status (SES) and geographic context are also considered.This study examined whether social environment attenuates racial disparities in SLE-related mortality using race-geographical combinations of the US population known as the "Eight Americas." This framework jointly characterizes race, SES, and geographical location in relation to health disparities in the United States. Using National Vital Statistics and US Census data, we estimated mortality parameters for each of the Eight Americas.We identified 24 773 SLE deaths (2003-2014). Average annual mortality rates were highest among blacks in three race-geographical contexts: average-income blacks, southern low-income blacks, and high-risk urban blacks (14 to 15 deaths per million population) and lowest among nonblacks living in average-income settings (3 to 4 deaths per million population). Age at death was lowest (~47.5 years) for blacks and Asians and highest among low-income rural whites (~64.8 years).Blacks sharing the same social and geographical contexts as whites were disproportionately more likely to die young. Although blacks inhabited three vastly different contexts, SLE-related mortality parameters did not vary among socially advantaged and disadvantaged blacks. These findings suggest that race may transcend SES and geographical parameters as a key determinant of SLE-related mortality.

  View details for DOI 10.1002/acr2.1024

  View details for PubMedID 31777791

  View details for PubMedCentralID PMC6858029

• TNF-alpha inhibition for the treatment of cardiac sarcoidosis. Seminars in arthritis and rheumatism Baker, M. C., Sheth, K. n., Witteles, R. n., Genovese, M. C., Shoor, S. n., Simard, J. F. 2019

  Abstract

  Tumor necrosis factor alpha (TNF-α) inhibitors are increasingly being used for treating refractory cardiac sarcoidosis. There is a theoretical risk, however, that these therapies can worsen heart failure, and reports on efficacy and safety are lacking.We conducted a retrospective review of all cardiac sarcoidosis patients seen at Stanford University from 2009 to 2018. Data were collected on patient demographics, diagnostic testing, and treatment outcomes.We identified 77 cardiac sarcoidosis patients, of which 20 (26%) received TNF-α inhibitor treatment. The majority were treated for progressive heart failure or tachyarrhythmia, along with worsening imaging findings. All TNF-α inhibitor treated patients demonstrated meaningful benefit, as assessed by changes in advanced imaging, echocardiographic measures of cardiac function, and prednisone use.A large cohort (n = 77) of cardiac sarcoidosis patients has been treated at Stanford University. Roughly one-fourth of these patients (n = 20) received TNF-α inhibitors. Of these patients, none had worsening heart failure and all saw clinical benefit. These results help support the use of TNF-α inhibitors for the treatment of cardiac sarcoidosis based on real-world evidence and highlight the need for future prospective studies.

  View details for DOI 10.1016/j.semarthrit.2019.11.004

  View details for PubMedID 31806154

• Preterm Delivery Phenotypes in Systemic Lupus Erythematosus Pregnancies. American journal of perinatology Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. L. 2018

  Abstract

  OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at a greater risk of preterm delivery, many of which may be medically indicated (iatrogenic). We investigated preterm delivery phenotypes in SLE and general population comparators and assessed the role of preeclampsia.STUDY DESIGN: We used population-based Swedish Register data (2001-2013) and defined maternal SLE as ≥2 SLE-coded discharge diagnoses from the Patient Register with ≥1 coded by an appropriate specialist. Women from the general population were identified using the Total Population Register. Preterm delivery was defined as <37 weeks and separated into spontaneous and iatrogenic, as well as later versus extremely preterm (32 to <37 weeks vs. <32 weeks). Maternal comorbidity was assessed, and the proportion mediated by preeclampsia was calculated examining first, subsequent, and all pregnancies.RESULTS: Preterm delivery was more common in SLE for the first (22 vs. 6%) and subsequent (15 vs. 4%) pregnancies among 781 SLE-exposed pregnancies and 11,271 non-SLE pregnancies. Of SLE-exposed first births, 27% delivered before 32 weeks, and 90% were iatrogenic (compared with 47% of non-SLE first births).CONCLUSION: Preterm delivery complicates a greater proportion of SLE pregnancies than general population pregnancies, and a considerable proportion of risk is mediated through preeclampsia.

  View details for PubMedID 30477035

• Response to: 'Increased stroke incidence in systemic lupus erythematosus patients: risk factors or disease itself?' by Bruzzese and Zullo ANNALS OF THE RHEUMATIC DISEASES Arkema, E. V., Rossides, M., Von Euler, M., Svenungsson, E., Sjowall, C., Simard, J. F. 2018; 77 (10): e72

  View details for DOI 10.1136/annrheumdis-2017-212604

  View details for Web of Science ID 000446465700009

  View details for PubMedID 29146744

• Asthma in Children of Mothers With Systemic Lupus Erythematosus and the Role of Preterm Birth ARTHRITIS CARE & RESEARCH Rossides, M., Nguyen, C., Arkema, E. V., Simard, J. F. 2018; 70 (8): 1269–74

  Abstract

  Systemic lupus erythematosus (SLE) and asthma share inheritable IgE-related pathophysiology, but the association between maternal SLE and asthma in the offspring has not been explored. Our aim was to investigate the association between maternal SLE during pregnancy and childhood asthma and examine the role of preterm birth as a mediator of the association using Swedish register data.Information on 12,000 singleton live births (2001-2013) was collected from the Medical Birth Register. Childhood asthma was defined as at least 1 International Classification of Diseases-coded visit in the National Patient Register. Prevalent maternal SLE at delivery was identified from the Medical Birth Register and the National Patient Register. Risk ratios for asthma were estimated while controlling for confounders. Mediation analysis was used to estimate what percentage of the total effect can be explained by preterm birth (defined as either <34 or <37 weeks of gestation).We compared 775 children born to mothers with SLE with 11,225 born to mothers without SLE. Ninety seven children of mothers with SLE (13%) were diagnosed with asthma, compared to 1,211 in the unexposed group (11%). The risk ratio for childhood asthma was 1.46 (95% confidence interval 1.16-1.84). In mediation analysis, 20-29% of the total effect of SLE was explained by preterm birth.Prevalent maternal SLE during pregnancy is associated with an increased risk of asthma in the offspring. While preterm birth can explain a fair proportion of this association, additional unidentified mechanisms also likely play a role.

  View details for DOI 10.1002/acr.23472

  View details for Web of Science ID 000445049100019

  View details for PubMedID 29125902

  View details for PubMedCentralID PMC5945344

• DEMOGRAPHICS AND PRESENTING ORGAN INVOLVEMENT IN A COHORT OF PATIENTS WITH SARCOIDOSIS Sheth, K., Jeyashanmugaraja, G., Simard, J., Shoor, S. BMJ PUBLISHING GROUP. 2018: 509–10

  View details for DOI 10.1136/annrheumdis-2018-eular.6164

  View details for Web of Science ID 000444351001383

• Use of Administrative Databases to Assess Reproductive Health Issues in Rheumatic Diseases RHEUMATIC DISEASE CLINICS OF NORTH AMERICA Vinet, E., Chakravarty, E. F., Simard, J. F., Clowse, M. 2018; 44 (2): 327-+

  Abstract

  Administrative databases, registers, and other sources of big data can be interesting sources to address important research questions on reproduction in women with rheumatic diseases. There are many different types of administrative datasets worldwide, and it is important to understand the type of data present and unavailable in each dataset, validity and potential misclassification of data, and the ability to link maternal data with infant data. This article discusses the advantages and methodologic issues associated with administrative database use for the conduct of observational studies on reproductive issues in women with rheumatic diseases.

  View details for DOI 10.1016/j.rdc.2018.01.008

  View details for Web of Science ID 000431283500012

  View details for PubMedID 29622299

• Autoantibody Profiling in Lupus Patients using Synthetic Nucleic Acids SCIENTIFIC REPORTS Klecka, M., Thybo, C., Macaubas, C., Solov'yov, I., Simard, J., Balboni, I., Fox, E., Voss, A., Mellins, E. D., Astakhova, K. 2018; 8: 5554

  Abstract

  Autoantibodies to nuclear components of cells (antinuclear antibodies, ANA), including DNA (a-DNA), are widely used in the diagnosis and subtyping of certain autoimmune diseases, including systemic lupus erythematosus (SLE). Despite clinical use over decades, precise, reproducible measurement of a-DNA titers remains difficult, likely due to the substantial sequence and length heterogeneity of DNA purified from natural sources. We designed and tested a panel of synthetic nucleic acid molecules composed of native deoxyribonucleotide units to measure a-DNA. ELISA assays using these antigens show specificity and reproducibility. Applying the ELISA tests to serological studies of pediatric and adult SLE, we identified novel clinical correlations. We also observed preferential recognition of a specific synthetic antigen by antibodies in SLE sera. We determined the probable basis for this finding using computational analyses, providing valuable structural information for future development of DNA antigens. Synthetic nucleic acid molecules offer the opportunity to standardize assays and to dissect antibody-antigen interactions.

  View details for PubMedID 29615791

• Hydroxychloroquine and Preeclampsia Risk in Pregnancies with Systemic Lupus Erythematosus. Do, S. C., Simard, J. F., Druzin, M. L. SAGE PUBLICATIONS INC. 2018: 239A–240A

  View details for Web of Science ID 000429928200554

• Paid Family and Childbearing Leave Policies at Top US Medical Schools JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Riano, N. S., Linos, E., Accurso, E. C., Sung, D., Linos, E., Simard, J. F., Mangurian, C. 2018; 319 (6): 611–14

  View details for PubMedID 29450516

  View details for PubMedCentralID PMC5838606

• Do Death Certificates Underestimate the Burden of Rare Diseases? The Example of Systemic Lupus Erythematosus Mortality, Sweden, 2001-2013. Public health reports (Washington, D.C. : 1974) Falasinnu, T., Rossides, M., Chaichian, Y., Simard, J. F. 2018: 33354918777253

  Abstract

  OBJECTIVES: Mortality due to rare diseases, which are substantial sources of premature mortality, is underreported in mortality studies. The objective of this study was to determine the completeness of reporting systemic lupus erythematosus (SLE) as a cause of death.METHODS: In 2017, we linked data on a Swedish population-based cohort (the Swedish Lupus Linkage, 2001-2013) comprising people with SLE (n = 8560) and their matched general population comparators (n = 37717) to data from the Cause of Death Register. We reviewed death records of deceased people from the cohort (n = 5110) and extracted data on patient demographic characteristics and causes of death. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for not reporting SLE as a cause of death by using multivariable-adjusted logistic regression models.RESULTS: Of 1802 deaths among SLE patients in the study, 1071 (59%) did not have SLE reported on their death records. Most SLE decedents were aged 75-84 at death (n = 584, 32%), female (n = 1462, 81%), and born in Nordic countries (n = 1730, 96%). Decedents aged ≥85 at death were more likely to have SLE not reported on their death records than were decedents aged <50 (OR = 2.34; 95% CI, 1.48-3.68). Having renal failure listed as a cause of death decreased the likelihood of SLE not being reported on the death record (OR = 0.54; 95% CI, 0.40-0.73), whereas having cancer listed as a cause of death increased this likelihood (OR = 2.39; 95% CI, 1.85-3.07).CONCLUSIONS: SLE was greatly underreported as a cause of mortality on death records of SLE patients, particularly in older decedents and those with cancer, thereby underestimating the true burden of this disease. Public health resources need to focus on improving the recording of rare diseases in order to enhance the epidemiological utility of mortality data.

  View details for DOI 10.1177/0033354918777253

  View details for PubMedID 29928843

• The Representation of Gender and Race/Ethnic Groups in Randomized Clinical Trials of Individuals with Systemic Lupus Erythematosus. Current rheumatology reports Falasinnu, T. n., Chaichian, Y. n., Bass, M. B., Simard, J. F. 2018; 20 (4): 20

  Abstract

  This review evaluated gender and race/ethnic representation in randomized controlled trials (RCTs) of patients with systemic lupus erythematosus (SLE).Whites comprise 33% of prevalent SLE cases and comprised 51% of RCT enrollees. Blacks encompass 43% of prevalent SLE cases, but only represented 14% of RCT enrollees. Hispanics comprise 16% of prevalent SLE cases and 21% of RCT enrollees, while Asians comprise 13% of prevalent SLE cases and 10% of RCT enrollees. Males encompass 9% of SLE cases and 7% of RCT enrollees. The reporting and representation of males have remained stable over time, although their representation in RCTs is slighter lower than the prevalence of SLE in males. The representation of Hispanics, Asians, and Native Americans increased over time. However, the representation of blacks among RCT participants has decreased since 2006-2011. RCTs among SLE patients need larger sample sizes in order to evaluate heterogeneity in outcomes among racial subgroups. It is imperative that novel strategies be developed to recruit racial minorities with SLE by identifying and improving barriers to RCT enrollment in order to better understand the disease's diverse population.

  View details for PubMedID 29550947

• Mortality and Functionality after Stroke in Patients with Systemic Lupus Erythematosus JOURNAL OF RHEUMATOLOGY Rossides, M., Simard, J. F., Svenungsson, E., von Euler, M., Arkema, E. V. 2017; 44 (11): 1590–96

  Abstract

  To investigate mortality and functional impairment after stroke in systemic lupus erythematosus (SLE).Using Swedish nationwide registers, we identified 423 individuals with SLE and 1652 people without SLE who developed a first-ever ischemic or hemorrhagic stroke (1998-2013) and followed them until all-cause death or for 1 year. HR for death after ischemic or hemorrhagic stroke and the risk ratio of functional impairment (dependence in either transferring, toileting, or dressing) 3 months after ischemic stroke were estimated.One year after stroke, 22% of patients with SLE versus 16% of those without SLE died. After ischemic stroke, patients with SLE had an increased risk of death (HR 1.85, 95% CI 1.39-2.45), which was attenuated after controlling for SLE-related comorbidities (HR 1.41, 95% CI 1.04-1.91). Functional impairment at 3 months was increased in SLE by almost 2-fold (risk ratio 1.73, 95% CI 1.16-2.57). After hemorrhagic stroke, patients with SLE had an HR of 2.30 (95% CI 1.38-3.82) for death, which was increased even during the first month.Compared to subjects without SLE, mortality after ischemic stroke increases after the first month in individuals with SLE, and functionality is worse at 3 months. SLE is associated with all-cause death after hemorrhagic stroke even during the first month. A shift of focus to patient functionality and prevention of hemorrhagic strokes is required.

  View details for PubMedID 28916550

• Determinants of Anti-Tumor Necrosis Factor Drug Use in Juvenile Spondyloarthropathy and Impact on Clinical Disease Outcomes Oliver, M., Simard, J. F., Gerstbacher, D., Lee, T., Sandborg, C. WILEY. 2017

  View details for Web of Science ID 000411824105128

• Unraveling Race and Social Context in Understanding Disparities in Lupus Mortality in the United States Falasinnu, T., Chaichian, Y., Palaniappan, L., Simard, J. F. WILEY. 2017

  View details for Web of Science ID 000411824101112

• Do Death Certificates Underestimate the Burden of Rare Diseases: The Example of Systemic Lupus Erythematosus Mortality in Sweden Falasinnu, T., Rossides, M., Chaichian, Y., Simard, J. F. WILEY. 2017

  View details for Web of Science ID 000411824101269

• Rates of New-Onset Pulmonary Disease Among Patients with Systemic Lupus Erythematosus in Sweden Forbess, L. J., Weisman, M., Simard, J. F. WILEY. 2017

  View details for Web of Science ID 000411824101121

• Preterm Delivery Phenotypes in SLE Pregnancies Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. WILEY. 2017

  View details for Web of Science ID 000411824102208

• Preterm Birth Phenotypes in Women with Autoimmune Diseases Kolstad, K. D., Mayo, J. A., Chung, L., Chaichian, Y., Kelly, V. M., Druzin, M., Stevenson, D. K., Shaw, G. M., Simard, J. F. WILEY. 2017

  View details for Web of Science ID 000411824102207

• Stroke in systemic lupus erythematosus: a Swedish population-based cohort study. Annals of the rheumatic diseases Arkema, E. V., Svenungsson, E., von Euler, M., Sjöwall, C., Simard, J. F. 2017

  Abstract

  To study the occurrence of ischaemic and haemorrhagic stroke in systemic lupus erythematosus (SLE) compared with the general population by age, sex and time since SLE diagnosis METHODS: Adults with incident SLE were identified from the Swedish National Patient Register (NPR, n=3390) and general population comparators from the Total Population Register were matched on age, sex and county (n=16730). Individuals were followed prospectively until first of death, December 2013, emigration or incident stroke (identified from the NPR, Cause of Death Register and the Stroke Register). Incidence rates, rate differences and HR were estimated comparing SLE with non-SLE. Estimates were stratified by sex, age and time since diagnosis.We observed 126 strokes in SLE and 304 in the general population. Individuals with SLE had a twofold increased rate of ischaemic stroke compared with the general population (HR 2.2; 95% CI 1.7 to 2.8). The HR for intracerebral haemorrhage was 1.4 (95% CI 0.7 to 2.8). There was effect modification by sex and age, with the highest HRs for females and individuals <50 years old. The HR for ischaemic stroke was highest in the first year of follow-up (3.7; 95% CI 2.1 to 6.5).The relative risk of ischaemic stroke in SLE was more than doubled compared with the general population, and importantly, the highest relative risks were observed within the first year after SLE diagnosis. Thus, the first encounter with patients presents an opportunity for rheumatologists to screen for risk factors and intervene.

  View details for DOI 10.1136/annrheumdis-2016-210973

  View details for PubMedID 28400384

• Cervical neoplasia in systemic lupus erythematosus: a nationwide study RHEUMATOLOGY Wadstrom, H., Arkema, E. V., Sjowall, C., Askling, J., Simard, J. F. 2017; 56 (4): 613-619

  View details for DOI 10.1093/rheumatology/kew459

  View details for Web of Science ID 000398497700018

• Medication use among pregnant women with systemic lupus erythematosus and general population comparators RHEUMATOLOGY Palmsten, K., Simard, J. F., Chambers, C. D., Arkema, E. V. 2017; 56 (4): 561-569

  Abstract

  The aim was to characterize SLE medication trends before, during and after pregnancy and to compare other commonly used medications during SLE pregnancies with non-SLE pregnancies.Women with pregnancies ending in live birth or stillbirth were identified from the Swedish Medical Birth Register (2006-12). National registers were used to identify women with prevalent SLE during pregnancy and a sample without SLE and to identify prescription medications dispensed from 3 months pre-pregnancy until 6 months postpartum. We reported the prevalence of DMARDs, systemic CSs and NSAIDs (aspirin reported separately) in SLE pregnancies. We calculated prevalence estimates of other medications that were dispensed during pregnancy to ⩾ 5% of SLE pregnancies and for the same medications among non-SLE pregnancies.There were 483 pregnancies among women with SLE and 5723 pregnancies among women without SLE. In SLE pregnancies, 49.3% had one or more dispensing for DMARDs during pregnancy; the prevalence was 48.0% for CSs, 40.8% for aspirin and 6.0% for other NSAIDs and varied by pregnancy period. The prevalence of common medications among SLE pregnancies was 1.2- to 20-fold higher than among non-SLE pregnancies; for example, dalteparin (20.9 vs 1.0%), paracetamol (18.2 vs 2.9%) and levothyroxine (15.9 vs 4.9%).In nearly half of SLE pregnancies, women were dispensed DMARDs and CSs. Commonly used medications in SLE pregnancies had far higher prevalence estimates compared with non-SLE pregnancies. Research regarding benefits and risks of commonly used medications on SLE pregnancies, breast milk and long-term outcomes for offspring is needed.

  View details for DOI 10.1093/rheumatology/kew448

  View details for Web of Science ID 000398497700011

• Early-onset Preeclampsia in Lupus Pregnancy PAEDIATRIC AND PERINATAL EPIDEMIOLOGY Simard, J. F., Arkema, E. V., Nguyen, C., Svenungsson, E., Wikstrom, A., Palmsten, K., Salmon, J. E. 2017; 31 (1): 29-36

  Abstract

  Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that occurs during childbearing years and has been associated with preeclampsia. However, little is known about preeclampsia of early onset, which is associated with severe adverse maternal and perinatal outcomes.Using national population-based Swedish registers we identified women with SLE (≥2 visits with corresponding ICD codes) and a sample without SLE who gave birth to singleton infants 2001-12. Risk ratios (RR) and 95% confidence intervals (CI) for early-onset preeclampsia (defined by ICD codes corresponding to preeclampsia registered at <34 weeks) in SLE women were calculated based on adjusted modified Poisson models for first, subsequent, and all pregnancies.Among 742 births to women with SLE and 10 484 births to non-SLE women, there were 32 (4.3%) and 55 (0.5%) diagnoses of early-onset preeclampsia respectively. SLE was associated with an increased risk of early-onset preeclampsia (RR 7.8, 95% CI 4.8, 12.9, all pregnancies). The association remained similar upon restriction to women without pregestational hypertension. Adjustment for antiphospholipid syndrome (APS)-proxy attenuated the association. RRs for early-onset preeclampsia were smaller for subsequent pregnancies (RR 4.7, 95% CI 2.0, 11.2) compared to first and all (see above).Women with SLE are at increased risk of early-onset preeclampsia and this increased risk may be independent of the traditional risk factors such as pregestational hypertension, APS, BMI, or smoking. Women with SLE during pregnancy should be closely monitored for early-onset preeclampsia and future research needs to identify the non-traditional preeclampsia factors that might cause this serious outcome.

  View details for DOI 10.1111/ppe.12332

  View details for Web of Science ID 000392509800006

  View details for PubMedID 27943386

• Sex Ratio of Offspring Born to Women With Systemic Lupus Erythematosus or Rheumatoid Arthritis ARTHRITIS & RHEUMATOLOGY Arkema, E. V., Askling, J., Salmon, J. E., Simard, J. F. 2017; 69 (1): 143-147

  View details for DOI 10.1002/art.39843

  View details for Web of Science ID 000392505500018

• Brief Report: Sex Ratio of Offspring Born to Women With Systemic Lupus Erythematosus or Rheumatoid Arthritis. Arthritis & rheumatology (Hoboken, N.J.) Arkema, E. V., Askling, J., Salmon, J. E., Simard, J. F. 2017; 69 (1): 143-147

  Abstract

  To determine whether the sex ratio among offspring born to women with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) is different from that in the general population.Women with a singleton delivery were identified from the Swedish Medical Birth Register (1973-2012) and linked to the National Patient Register (1964-2012) to identify those with prevalent SLE or RA. A sample of general population comparators was identified from the Swedish Total Population Register. We calculated the percentages of males born to women with SLE, women with RA, and women in the general population, as well as the risk ratio (RR) for having a male child among first births and all births. We also examined a history of antiphospholipid syndrome in the SLE population, using International Classification of Disease codes before or at delivery.We identified 661 women with SLE and 1,136 women with RA before their first delivery. There were a total of 1,401 deliveries to women with SLE and a total of 2,674 deliveries to women with RA. Compared with women in the general population, women with SLE and those with RA had a lower risk of having a first-born male (RR 0.92 [95% confidence interval 0.85-1.00] and RR 0.93 [95% confidence interval 0.87-0.99], respectively). Among all births, the percentage of male offspring remained lower than that in the general population, but the difference was not statistically significant for RA.The proportion of male offspring born to women with prevalent SLE or RA at delivery was lower than that in the general population, although the difference was small. Chronic inflammation may affect the sex ratio through fetal loss in early gestation.

  View details for DOI 10.1002/art.39843

  View details for PubMedID 27564656

• Cervical neoplasia in systemic lupus erythematosus: a nationwide study. Rheumatology (Oxford, England) Wadström, H., Arkema, E. V., Sjöwall, C., Askling, J., Simard, J. F. 2016

  Abstract

  The aim was to examine the risk of cervical neoplasia in women with SLE, overall and with respect to treatment, compared with women from the general population.By linking national Swedish registers, we assembled a cohort including women with SLE (n = 4976) and matched general population comparators (n = 29 703). Two subcohorts of treated SLE patients were defined on the basis of treatment with antimalarials (n = 1942) and other immunosuppressants (AZA, CYC, ciclosporin, MTX, MMF or rituximab; n = 2175). The main outcome was defined as a first cervical neoplasia (dysplasia or cancer) during follow-up. Secondary outcomes were first cervical intraepithelial neoplasia (CIN) 1; first CIN grades 2-3; and first invasive cervical cancer during follow-up (2006-12). Cox regression models estimated relative risks adjusted for age, level of education, health-care utilization, number of children, marital status, family history of cervical cancer and prior cervical screening.Based on 121 events of cervical neoplasia during 23 136 person-years among SLE patients, there was an increased risk of any cervical neoplasia compared with the general population [hazard ratio (HR) = 2.12 (95% CI: 1.65, 2.71)]. The risk of CIN 1 [HR = 2.33 (95% CI: 1.58, 3.44)], CIN 2-3 [HR = 1.95 (95% CI: 1.43, 2.65)], but not invasive cervical cancer [HR = 1.64 (95% CI: 0.54, 5.02)], was increased in women with SLE. The subcohort treated with other immunosuppressants was at highest risk of cervical neoplasia.SLE is a risk factor for cervical neoplasia, in particular for pre-malignant cervical lesions. Among patients with SLE, the risk is higher among those treated with immunosuppresants compared with those treated with antimalarials.

  View details for DOI 10.1093/rheumatology/kew459

  View details for PubMedID 28039412

• Medication use among pregnant women with systemic lupus erythematosus and general population comparators. Rheumatology (Oxford, England) Palmsten, K., Simard, J. F., Chambers, C. D., Arkema, E. V. 2016

  Abstract

  The aim was to characterize SLE medication trends before, during and after pregnancy and to compare other commonly used medications during SLE pregnancies with non-SLE pregnancies.Women with pregnancies ending in live birth or stillbirth were identified from the Swedish Medical Birth Register (2006-12). National registers were used to identify women with prevalent SLE during pregnancy and a sample without SLE and to identify prescription medications dispensed from 3 months pre-pregnancy until 6 months postpartum. We reported the prevalence of DMARDs, systemic CSs and NSAIDs (aspirin reported separately) in SLE pregnancies. We calculated prevalence estimates of other medications that were dispensed during pregnancy to ⩾ 5% of SLE pregnancies and for the same medications among non-SLE pregnancies.There were 483 pregnancies among women with SLE and 5723 pregnancies among women without SLE. In SLE pregnancies, 49.3% had one or more dispensing for DMARDs during pregnancy; the prevalence was 48.0% for CSs, 40.8% for aspirin and 6.0% for other NSAIDs and varied by pregnancy period. The prevalence of common medications among SLE pregnancies was 1.2- to 20-fold higher than among non-SLE pregnancies; for example, dalteparin (20.9 vs 1.0%), paracetamol (18.2 vs 2.9%) and levothyroxine (15.9 vs 4.9%).In nearly half of SLE pregnancies, women were dispensed DMARDs and CSs. Commonly used medications in SLE pregnancies had far higher prevalence estimates compared with non-SLE pregnancies. Research regarding benefits and risks of commonly used medications on SLE pregnancies, breast milk and long-term outcomes for offspring is needed.

  View details for DOI 10.1093/rheumatology/kew448

  View details for PubMedID 28013193

• The Rheumatology Informatics System for Effectiveness (RISE): A National Informatics-Enabled Registry for Quality Improvement. Arthritis care & research Yazdany, J., Bansback, N., Clowse, M., Collier, D., Law, K., Liao, K. P., Michaud, K., Morgan, E. M., Oates, J. C., Orozco, C., Reimold, A., Simard, J. F., Myslinski, R., Kazi, S. 2016

  Abstract

  The Rheumatology Informatics System for Effectiveness (RISE) is a national electronic health record (EHR)-enabled registry. RISE passively collects data from EHRs of participating practices, provides advanced quality measurement and data analytic capacities, and fulfills national quality reporting requirements. Here we report the registry's architecture and initial data, and we demonstrate how RISE is being used to improve the quality of care.RISE is a certified Centers for Medicare and Medicaid Services Qualified Clinical Data Registry, allowing collection of data without individual patient informed consent. We analyzed data between October 1, 2014 and September 30, 2015 to characterize initial practices and patients captured in RISE. We also analyzed medication use among rheumatoid arthritis (RA) patients and performance on several quality measures.Across 55 sites, 312 clinicians contributed data to RISE; 72% were in group practice, 21% in solo practice, and 7% were part of a larger health system. Sites contributed data on 239,302 individuals. Among the subset with RA, 34.4% of patients were taking a biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) at their last encounter, and 66.7% were receiving a nonbiologic DMARD. Examples of quality measures include that 55.2% had a disease activity score recorded, 53.6% a functional status score, and 91.0% were taking a DMARD in the last year.RISE provides critical infrastructure for improving the quality of care in rheumatology and is a unique data source to generate new knowledge. Data validation and mapping are ongoing and RISE is available to the research and clinical communities to advance rheumatology.

  View details for DOI 10.1002/acr.23089

  View details for PubMedID 27696755

• Endometriosis and systemic lupus erythematosus: a population-based case-control study. Lupus Harris, H. R., Simard, J. F., Arkema, E. V. 2016; 25 (9): 1045-1049

  Abstract

  To investigate the association between endometriosis and systemic lupus erythematosus (SLE) in prospectively collected population-based data.We conducted a case-control study using Swedish registers, identifying female SLE cases from the National Patient Register and female controls sampled from the general population matched on birth year, sex and county during 1964-2011. We identified endometriosis diagnoses from the National Patient Register using ICD codes. We estimated odds ratios and 95% confidence intervals using conditional logistic regression models.We identified 2834 cases of SLE and 14,164 controls. Seventy-eight cases were diagnosed with endometriosis prior to their SLE diagnosis and 288 controls were diagnosed prior to the index date. We observed a significant association between endometriosis and subsequent SLE with an odds ratio of 1.39 (95% confidence interval = 1.09-1.78). The association was similar when requiring a laparoscopy/laparotomy within six months of the endometriosis diagnosis (odds ratio = 1.33; 95% confidence interval = 0.84-2.12) while the association was stronger when restricted to endometriosis diagnosed at the same time as hysterectomy (odds ratio = 2.26; 95% confidence interval = 1.47-3.64).Our findings suggest an association between endometriosis and SLE. Future prospective studies with extended follow-up will be necessary to clarify whether this association is influenced by the timing and severity of endometriosis diagnosis.

  View details for DOI 10.1177/0961203316631635

  View details for PubMedID 26854081

  View details for PubMedCentralID PMC4945380

• What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population-Based Study of Maternal and Fetal Outcomes in SLE and Pre-SLE ARTHRITIS CARE & RESEARCH Arkema, E. V., Palmsten, K., Sjowall, C., Svenungsson, E., Salmon, J. E., Simard, J. F. 2016; 68 (7): 988-994

  Abstract

  To assess maternal and fetal outcomes associated with subclinical (pre-systemic lupus erythematosus [SLE] and SLE presenting up to 5 years postpartum) and prevalent maternal SLE during pregnancy compared with the general population.This prospective cohort study used population-based Swedish registers to identify 13,598 women with first singleton pregnancies registered in the Medical Birth Register (551 prevalent SLE, 65 pre-SLE within 0-2 years, 133 pre-SLE within 2-5 years, and 12,847 general population). SLE was defined as ≥2 SLE-coded discharge diagnoses in the patient register with ≥1 diagnosis from a specialist. Unadjusted risks of adverse pregnancy or birth outcomes were calculated by SLE status, and Cochran-Armitage tests evaluated trend across exposure groups.Maternal outcomes such as preeclampsia, hypothyroidism, stroke, and infection were more common among women with SLE. Sixteen percent of prevalent-SLE pregnancies were diagnosed with preeclampsia compared with 5% of those from the general population. Among the pre-SLE women, preeclampsia was found in 26% of those with SLE within 2 years postpartum and 13% in those with SLE within 2-5 years postpartum. Similarly, infant outcomes, such as preterm birth, infection, and mortality, were worse among those born to mothers with prevalent SLE and pre-SLE during pregnancy. The test for trend was significant for most outcomes.Our data demonstrate that adverse maternal and fetal outcomes are more common in SLE pregnancies. Furthermore, these unfavorable outcomes are observed in pregnancies occurring prior to the diagnosis of SLE. Thus, the underlying immunologic profile of SLE and alterations preceding clinical SLE may contribute to these pregnancy complications.

  View details for DOI 10.1002/acr.22791

  View details for Web of Science ID 000379673700013

  View details for PubMedID 27338103

• What is the impact of chronic systemic inflammation such as rheumatoid arthritis on mortality following cancer? Annals of the rheumatic diseases Simard, J. F., Ekberg, S., Johansson, A. L., Askling, J. 2016; 75 (5): 862-866

  Abstract

  Emerging evidence links inflammation and immune competence to cancer progression and outcome. Few studies addressing cancer survival in the context of rheumatoid arthritis (RA) have reported reduced survival without accounting for the underlying mortality risk in RA. Whether this increased mortality is a cancer-specific phenomenon, an effect of the decreased lifespan in RA or a combination of both remains unknown.Using Swedish register data (2001-2009), we performed a cohort study of individuals with RA (N=34 930), matched to general population comparators (N=169 740), incident cancers (N=12 676) and deaths (N=14 291). Using stratified Cox models, we estimated HRs of death associated with RA in the presence and absence of cancer, by stage and time since cancer diagnosis, for all cancers and specific sites.In the absence of cancer, RA was associated with a doubled mortality rate (HR=2.1, 95% CI 2.0 to 2.2). In the presence of cancer, the relative effect of RA on mortality was varied by stage. For cancer (tumour, node, metastases) stages I and II at diagnosis, the relative effect of RA on mortality was the same as in the absence of cancer. For cancers diagnosed at advanced stages with absolute higher mortality, the effect decreased (HR=1.2, 95% CI 1.1 to 1.3). These associations remained across time since cancer diagnosis and were reasonably similar across cancer sites.Much of the increase in mortality in patients with RA diagnosed with cancer seems to reside with effects of RA independently of the cancer.

  View details for DOI 10.1136/annrheumdis-2014-207155

  View details for PubMedID 25948597

• Case definitions in Swedish register data to identify systemic lupus erythematosus. BMJ open Arkema, E. V., Jönsen, A., Rönnblom, L., Svenungsson, E., Sjöwall, C., Simard, J. F. 2016; 6 (1)

  Abstract

  To develop and investigate the utility of several different case definitions for systemic lupus erythematosus (SLE) using national register data in Sweden.The reference standard consisted of clinically confirmed SLE cases pooled from four major clinical centres in Sweden (n=929), and a sample of non-SLE comparators randomly selected from the National Population Register (n=24,267). Demographics, comorbidities, prescriptions and autoimmune disease family history were obtained from multiple registers and linked to the reference standard. We first used previously published SLE definitions to create algorithms for SLE. We also used modern data mining techniques (penalised least absolute shrinkage and selection operator logistic regression, elastic net regression and classification trees) to objectively create data-driven case definitions. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the case definitions identified.Defining SLE by using only hospitalisation data resulted in the lowest sensitivity (0.79). When SLE codes from the outpatient register were included, sensitivity and PPV increased (PPV between 0.97 and 0.98, sensitivity between 0.97 and 0.99). Addition of medication information did not greatly improve the algorithm's performance. The application of data mining methods did not yield different case definitions.The use of SLE International Classification of Diseases (ICD) codes in outpatient clinics increased the accuracy for identifying individuals with SLE using Swedish registry data. This study implies that it is possible to use ICD codes from national registers to create a cohort of individuals with SLE.

  View details for DOI 10.1136/bmjopen-2015-007769

  View details for PubMedID 26729375

• Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden. BMJ (Clinical research ed.) Raaschou, P., Simard, J. F., Asker Hagelberg, C., Askling, J. 2016; 352: i262-?

  Abstract

  To investigate the risk of squamous cell and basal cell skin cancer in patients with rheumatoid arthritis naive to biologic drugs, in patients starting tumour necrosis factor (TNF) inhibitor treatment, and in the general population.Population based cohort study.Nationwide data from Sweden.Cohort of patients with rheumatoid arthritis naive to biologics (n=46 409), cohort of patients with rheumatoid arthritis starting TNF inhibitor treatment as first biologic in 1998-2012 (n=12 558), and matched general population comparator cohort, identified through national quality of care and health registers.Hazard ratio of first in situ or invasive squamous cell skin cancer (1998-2012) and first basal cell cancer (2004-12).For basal cell cancer, the hazard ratio was 1.22 (95% confidence interval 1.07 to 1.41) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.14 (0.98 to 1.33; 236 v 1587 events) comparing TNF inhibitor treated patients with biologics-naive patients. For squamous cell cancer, the hazard ratio was 1.88 (1.74 to 2.03) comparing biologics-naive rheumatoid arthritis patients with the general population and 1.30 (1.10 to 1.55; 191 v 847 events) comparing TNF inhibitors with biologics-naive patients; the latter translated to an annual number needed to harm in the order of 1600. Among people with a history of squamous cell or basal cell cancer, TNF inhibitors did not further increase risks.A small to moderately increased risk of basal cell cancer was seen in biologics-naive rheumatoid arthritis patients, with no further effect of TNF inhibitors. For squamous cell cancer, the risk was nearly doubled in biologics-naive patients, with a further 30% increase in risk among patients treated with TNF inhibitors; this translates to one additional case for every 1600 years of treatment experience, assuming that this association reflected causality. Vigilance regarding skin malignancies may be advisable in rheumatoid arthritis, irrespective of TNF inhibitor treatment. Most of the increase in risk for non-melanoma skin cancer in patients with rheumatoid arthritis treated with TNF inhibitors originates from factors other than that treatment.

  View details for DOI 10.1136/bmj.i262

  View details for PubMedID 26823527

• Perinatal risk factors for future SLE: a population-based nested case-control study LUPUS Arkema, E. V., Simard, J. F. 2015; 24 (8): 869-874

  Abstract

  To investigate the association between perinatal characteristics and the offspring's risk of lupus using population-based registers in Sweden.We conducted a nested case-control study, identifying systemic lupus erythematosus (SLE) cases from the National Patient Register and controls sampled from the general population matched on birth year, sex, and residential county. We obtained data on the mother's health and age during pregnancy and characteristics of labor and delivery from the Medical Birth Register (births from 1973 through 2008) for cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression models overall and separately for males and females.We identified 774 cases and 3337 controls. Age at which SLE was first observed ranged from 0 to 36 years old. High birth weight was not a risk factor for SLE and did not differ by sex. Males had a 2.4-fold increased odds of SLE if born preterm (<37 weeks; OR = 2.41; 95% CI 1.09, 5.36). Birth order was significantly associated with SLE, particularly among females (first born vs. not OR = 0.77, 95% CI 0.64, 0.94; continuous birth order OR = 1.12. 95% CI 1.02, 1.24).Being born first was associated with reduced odds of SLE and the odds of SLE increased by 12% for every additional birth. Preterm birth was associated with increased odds in males only. Unlike previous work, high birth weight was not a risk factor for SLE.

  View details for DOI 10.1177/0961203315570160

  View details for Web of Science ID 000356233900012

  View details for PubMedID 25672372

• Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalimumab, etanercept and infliximab ANNALS OF THE RHEUMATIC DISEASES Neovius, M., Arkema, E. V., Olsson, H., Eriksson, J. K., Kristensen, L. E., Simard, J. F., Askling, J. 2015; 74 (2): 354-360

  Abstract

  To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA).Patients with RA (n=9139; 76% women; mean age 56 years) starting their first tumour necrosis factor (TNF) inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5 years of follow-up was compared overall and by period of treatment start (2003-2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period, health assessment questionnaire (HAQ), disease duration, concomitant disease modifying antirheumatic drug (DMARD) treatment and general frailty (using hospitalisation history as proxy).During 20 198 person-years (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to 1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI 1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but were modified by time for adalimumab versus etanercept (p<0.001; between-drug difference highest the 1st year in both periods). The discontinuation rate was higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to 1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs 2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased from 43% to 53% (p<0.001).Discontinuation rates were higher for infliximab compared with adalimumab and etanercept initiators, and for adalimumab versus etanercept during the 1st year. Discontinuation rates increased with calendar period, as did the percentage discontinuations due to inefficacy.

  View details for DOI 10.1136/annrheumdis-2013-204128

  View details for Web of Science ID 000347458300007

  View details for PubMedID 24285495

• Cohort profile: systemic lupus erythematosus in Sweden: the Swedish Lupus Linkage (SLINK) cohort. BMJ open Arkema, E. V., Simard, J. F. 2015; 5 (8)

  Abstract

  A cohort of individuals with systemic lupus erythematosus (SLE) was identified through linkage of several national registers to investigate important epidemiological questions using not only population-based data to minimise selection bias, but also to identify matched comparators from the general population to serve as controls. This cohort was established to overcome the general dearth of data in SLE epidemiology.All individuals registered in Sweden with a personal identity number and who have obtained medical care at any hospital or public non-primary outpatient specialist care with suspected SLE were identified. Inpatient register data date back to the 1960s, although complete national coverage of the inpatient register was achieved in 1987. In 2001, the outpatient component was also added to the register, representing the entire country of Sweden. For each suspected individual with SLE, up to five individuals from the general population were identified and matched on sex, birth year and county of residence.We have linked this study population to a number of national and quality registers in Sweden to identify first-degree relatives, deaths, births, dispensed prescriptions, comorbidities and disease end points, such as stroke and cancer, as well as basic health economic data. We found geographic variability in the prevalence of SLE by county. We have also shown that being first-born confers a reduced odds of having SLE in childhood and early adulthood.In addition to updating the national register linkage with several more years of follow-up data, we are adding several quality registers in Sweden, including the Tuberculosis register and the Social Insurance Office database. While these updates are ongoing and additional follow-up accumulates, we are studying a number of outcomes in SLE, including stroke, pregnancy and death. We will continue to present findings at scientific conferences and in the peer-reviewed literature.

  View details for DOI 10.1136/bmjopen-2015-008259

  View details for PubMedID 26275903

• Stroke in systemic lupus erythematosus: a meta-analysis of population-based cohort studies. RMD open Holmqvist, M., Simard, J. F., Asplund, K., Arkema, E. V. 2015; 1 (1)

  Abstract

  Previous studies of stroke in systemic lupus erythematosus (SLE) have had limited statistical power, combined stroke subtypes into composite outcomes, and lacked a reference population estimate. Therefore, we conducted a systematic review and meta-analysis of cohort studies to summarise the stroke subtype-specific risk in patients with SLE compared to the general population. A systematic search of MEDLINE and EMBASE was performed for cohort studies examining the risk of stroke in SLE and including a general population comparator. Random effects models were used to pool the risk ratio (RR) for stroke. Subgroup analyses were carried out to investigate potential sources of heterogeneity. 10 studies were included which reported RRs for overall stroke (n=5), ischaemic stroke (n=6), intracerebral haemorrhage (n=3) and subarachnoid haemorrhage (n=3). The pooled RR for overall stroke was 2.53 (95% CI 1.96 to 3.26), ischaemic stroke 2.10 (95% CI 1.68 to 2.62), intracerebral haemorrhage 2.72 (95% CI 2.15 to 3.44) and subarachnoid haemorrhage 3.85 (95% CI 3.20 to 4.64). Significant heterogeneity among studies for ischaemic stroke was detected (p=0.002). Relative risk of stroke was highest among individuals younger than 50 years of age. Individuals with SLE have a twofold higher risk of ischaemic stroke, a threefold higher risk of intracerebral haemorrhage, and an almost fourfold higher risk of subarachnoid haemorrhage compared to the general population. Future studies should focus on whether comorbidity and disease flares are related to stroke, when individuals are at the highest risk, and how the targeting of specific groups of patients with SLE may reduce this risk.

  View details for DOI 10.1136/rmdopen-2015-000168

  View details for PubMedID 26719816

• Systemic lupus erythematosus prevalence in Sweden in 2010: what do national registers say? Arthritis care & research Simard, J. F., Sjöwall, C., Rönnblom, L., Jönsen, A., Svenungsson, E. 2014; 66 (11): 1710-1717

  Abstract

  Worldwide prevalence estimates of systemic lupus erythematosus (SLE) range from 3 to 207 per 100,000, depending on region and population, SLE definition, case sources, and other methodologic considerations. We aimed to determine the prevalence of SLE in Sweden on January 1, 2010, using population-based registers.Linking multiple national registers, we identified all possible inpatient and outpatient visits with SLE-specific discharge diagnoses and relevant prescription dispensations among living individuals registered in Sweden on January 1, 2010. SLE was defined from a lenient classification (requiring only a single visit) to stricter definitions that required multiple visits with a history of relevant specialist care and a dispensation for common SLE medications. Prevalence was calculated overall and by sex, age (0-14 years, 15-49 years, and ≥50 years, as well as in 5-year age groups), and county of residence.Overall prevalence ranged from 46 per 100,000 for the strictest definition to 85 per 100,000 for the least strict definition. As expected, SLE was more common among females (range 79-144 per 100,000) than males (range 12-25 per 100,000) and varied by age. The up to 4-fold variation by county was unexpected. Prevalence generally increased with age (2, 52, and 95 per 100,000 by increasing age group, 0-14 years, 15-49 years, and ≥50 years, respectively, using a moderately strict definition) and also varied by county.Variations of prevalence by age and sex were consistent with previous studies and overall ranged from 46 to 85 per 100,000. We observed a surprising geographic variation in the prevalence of SLE in Sweden on January 1, 2010, according to multiple definitions.

  View details for DOI 10.1002/acr.22355

  View details for PubMedID 24757083

• Predictors of work disability during the first 3 years after diagnosis in a national rheumatoid arthritis inception cohort ANNALS OF THE RHEUMATIC DISEASES Olofsson, T., Petersson, I. F., Eriksson, J. K., Englund, M., Simard, J. F., Nilsson, J., Geborek, P., Jacobsson, L. T., Askling, J., Neovius, M. 2014; 73 (5): 845-853

  Abstract

  OBJECTIVE: To identify predictors of sick leave and disability pension in patients with early rheumatoid arthritis (RA). METHODS: Individuals aged 19-59 years diagnosed with early RA (≤12 months symptom duration) were identified in the Swedish Rheumatology Quality Register (1999-2007; n=3029). We retrieved days of sick leave and disability pension from the Swedish Social Insurance Agency and baseline predictors of total work days lost during 3 years after RA diagnosis were investigated using linear regression. Due to effect modification by baseline work ability (defined as work days lost the month before diagnosis), analyses were stratified into three categories: full=0 work days lost the month before diagnosis; partial=1-29 work days lost; and none=30 work days lost. RESULTS: 71% of patients with full baseline work ability still had full work ability after 3 years compared with 36% (p<0.001) and 18% (p<0.001) of those with partial and no work ability at baseline, respectively. Elevated baseline levels of HAQ and DAS28, higher age, lower education level and unemployment were associated with more work days lost during 3 years in all strata of baseline work ability (all p<0.05). In a separate analysis, more objective variables (ESR, CRP and swollen joints) were not. Generally, the largest regression coefficients were seen for patients with partial baseline work ability. CONCLUSIONS: Work ability at RA diagnosis was the most important predictor of 3-year sick leave and disability pension. Taking this into account, HAQ, DAS28, age and education level were also significant predictors, whereas ESR and CRP were not.

  View details for Web of Science ID 000333767300016

  View details for PubMedID 23520035

• Association of Varying Number of Doses of Quadrivalent Human Papillomavirus Vaccine With Incidence of Condyloma JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Herweijer, E., Leval, A., Ploner, A., Eloranta, S., Simard, J. F., Dillner, J., Netterlid, E., Sparen, P., Arnheim-Dahlstrom, L. 2014; 311 (6): 597-603

  Abstract

  Determining vaccine dose-level protection is essential to minimize program costs and increase mass vaccination program feasibility. Currently, a 3-dose vaccination schedule is recommended for both the quadrivalent and bivalent human papillomavirus (HPV) vaccines. Although the primary goal of HPV vaccination programs is to prevent cervical cancer, condyloma related to HPV types 6 and 11 is also prevented with the quadrivalent vaccine and represents the earliest measurable preventable disease outcome for the HPV vaccine.To examine the association between quadrivalent HPV vaccination and first occurrence of condyloma in relation to vaccine dose in a population-based setting.An open cohort of all females aged 10 to 24 years living in Sweden (n = 1,045,165) was followed up between 2006 and 2010 for HPV vaccination and first occurrence of condyloma using the Swedish nationwide population-based health data registers.Incidence rate ratios (IRRs) and incidence rate differences (IRDs) of condyloma were estimated using Poisson regression with vaccine dose as a time-dependent exposure, adjusting for attained age and parental education, and stratified on age at first vaccination. To account for prevalent infections, models included a buffer period of delayed case counting.A total of 20,383 incident cases of condyloma were identified during follow-up, including 322 cases after receipt of at least 1 dose of the vaccine. For individuals aged 10 to 16 years at first vaccination, receipt of 3 doses was associated with an IRR of 0.18 (95% CI, 0.15-0.22) for condyloma, whereas receipt of 2 doses was associated with an IRR of 0.29 (95% CI, 0.21-0.40). One dose was associated with an IRR of 0.31 (95% CI, 0.20-0.49), which corresponds to an IRD of 384 cases (95% CI, 305-464) per 100,000 person-years, compared with no vaccination. The corresponding IRDs for 2 doses were 400 cases (95% CI, 346-454) and for 3 doses, 459 cases (95% CI, 437-482). The number of prevented cases between 3 and 2 doses was 59 (95% CI, 2-117) per 100,000 person-years.Although maximum reduction in condyloma risk was seen after receipt of 3 doses of quadrivalent HPV vaccine, receipt of 2 vaccine doses was also associated with a considerable reduction in condyloma risk. The implications of these findings for the relationship between number of vaccine doses and cervical cancer risk require further investigation.

  View details for DOI 10.1001/jama.2014.95

  View details for Web of Science ID 000330941000015

  View details for PubMedID 24519299

• Challenges in understanding the role of pregnancy morbidity in cardiovascular risk in SLE. Lupus science & medicine Simard, J. F., Yazdany, J. 2014; 1 (1)

  View details for DOI 10.1136/lupus-2014-000035

  View details for PubMedID 25379195

• Lifestyle factors, autoimmune disease and family history in prognosis of non-hodgkin lymphoma overall and subtypes INTERNATIONAL JOURNAL OF CANCER Simard, J. F., Baecklund, F., Chang, E. T., Baecklund, E., Hjalgrim, H., Adami, H., Glimelius, B., Smedby, K. E. 2013; 132 (11): 2659-2666

  Abstract

  Lifestyle factors and medical history are known to influence risk of non-Hodgkin lymphoma (NHL). Whether these factors affect the prognosis of NHL, especially its subtypes, is unclear. To investigate this, the association between these factors and all-cause and lymphoma-related mortality was assessed in a population-based cohort of 1,523 Swedish NHL patients included in the Scandinavian Lymphoma Etiology study in 1999-2002. Participants contributed time from NHL diagnosis until death or October 1, 2010, with virtually complete follow-up through linkage to the Swedish Cause of Death Register. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using stratified and multivariable-adjusted Cox regression models. During a median follow-up of 8.8 years, 670 patients (44%) died, with the majority of deaths attributed to lymphoma (86%). Current versus never smoking at diagnosis was associated with increased rate of all-cause death for all NHL (HR = 1.5, 1.2-1.8) and diffuse large B-cell lymphoma (HR = 1.8, 1.2-2.7). Low educational level (HR = 1.3, 1.1-1.7, <9 vs. >12 years) and NHL risk-associated autoimmune disease (HR = 1.4, 1.0-1.8) were associated with death for all NHL combined. However, evidence of an association with lymphoma-related death was limited. Body mass index, recent sunbathing and family history of hematopoietic malignancy were not consistently associated with death after NHL or its specific subtypes. These results add to the evidence that cigarette smoking, socioeconomic status and certain autoimmune diseases affect survival after NHL. Further investigations are needed to determine how these factors should be incorporated into clinical prognostic assessment.

  View details for DOI 10.1002/ijc.27944

  View details for Web of Science ID 000316824000022

  View details for PubMedID 23160780

• Incidence of Rheumatoid Arthritis in Sweden: A Nationwide Population-Based Assessment of Incidence, Its Determinants, and Treatment Penetration ARTHRITIS CARE & RESEARCH Eriksson, J. K., Neovius, M., Ernestam, S., Lindblad, S., Simard, J. F., Askling, J. 2013; 65 (6): 870-878

  Abstract

  To estimate the nationwide incidence of rheumatoid arthritis (RA) in Sweden, including its variation across age, sex, geography, and demography, and to describe the sensitivity of register-based incidence estimates to different RA case definitions.Incident RA patients were identified using the Swedish National Patient Register. In the base case, incident RA was defined as first-ever inpatient or nonprimary outpatient care visit listing an RA diagnosis in 2006-2008, with a second visit listing RA within 1 year. Patients prescribed disease-modifying antirheumatic drugs more than 6 months prior to the first visit listing RA were not regarded as incident. The robustness of this definition was evaluated by more liberal and strict criteria, and by penetration of antirheumatic treatment.Between 2006 and 2008, 8,826 individuals were identified as incident RA patients. The overall incidence was 41 per 100,000 (56 for women, 25 for men). The incidence increased with age and peaked in the 70-79 years age group for both women and men. The age- and sex-standardized incidences were lower in densely populated areas and in individuals with high educational level. No geographic trends were noted. More liberal and strict definitions of RA only altered the observed incidence by approximately 14%.The overall nationwide register-based incidence of RA was robust across different case definitions. In a country with universal access to care, RA displayed demographic and socioeconomic, but no geographic, variations in incidence, and peaks at an older age than most commonly reported, with no difference in peak age at RA onset between sexes.

  View details for DOI 10.1002/acr.21900

  View details for Web of Science ID 000319758900006

  View details for PubMedID 23281173

• Reply. Arthritis and rheumatism Simard, J. F., Neovius, M., Askling, J. 2013; 65 (6): 1671-1672

  View details for DOI 10.1002/art.37929

  View details for PubMedID 23508884

• Increased risk of arthropathies and joint replacement surgery in patients with genetic hemochromatosis: a study of 3,531 patients and their 11,794 first-degree relatives. Arthritis care & research Elmberg, M., Hultcrantz, R., Simard, J. F., Carlsson, A., Askling, J. 2013; 65 (5): 678-685

  Abstract

  Genetic hemochromatosis (GH) is an autosomal recessive disease in individuals of Northern and Western European descent. Heterozygosity for the C282Y mutation is common (6-20%). Arthropathy is one of the few complications of GH suggested not to be associated with iron body stores; synovial iron deposition remains in iron-depleted patients. Previous studies suggest an elevated prevalence of clinical and radiographic signs of arthropathy in patients with GH, and 2 smaller studies suggest a possibly elevated risk of joint replacement surgery, but more mixed results are shown regarding risks with HFE genotype. We therefore assessed the risks of arthropathy and joint replacement surgery in patients with GH and in their first-degree relatives (FDRs).We performed a population-based cohort study of 3,531 patients with GH and of their 11,794 FDRs (assumed to be heterozygous for the C282Y mutation) using nationwide Swedish population-based health and census registers. Hazard ratios (HRs) of arthropathies and joint replacement surgeries among patients and their FDRs (versus the general population) were assessed using Cox regression.Between 1997 and 2005, 406 of 3,531 patients were reported/hospitalized with any noninfectious arthropathies, including osteoarthritis, corresponding to an HR of 2.38 (95% confidence interval [95% CI] 2.14-2.64). Patients were also at increased risk of hip replacement (HR 2.77, 95% CI 2.27-3.38) and knee replacement (HR 2.14, 95% CI 1.58-2.88) surgery. Among the 11,794 FDRs (patients excluded), we found no increased risk of any of the joint morbidities.Patients with GH, but not their FDRs, are at increased risk of arthropathies, including the need for joint replacement surgery.

  View details for DOI 10.1002/acr.21883

  View details for PubMedID 23139229

• Rheumatoid arthritis, anti-tumour necrosis factor therapy, and risk of malignant melanoma: nationwide population based prospective cohort study from Sweden BRITISH MEDICAL JOURNAL Raaschou, P., Simard, J. F., Holmqvist, M., Askling, J. 2013; 346

  Abstract

  To investigate the potential association between tumour necrosis factor (TNF) inhibitor treatment and malignant melanomas in rheumatoid arthritis, melanoma risks in rheumatoid arthritis patients not treated with biological drugs, and risk of all site cancer with TNF inhibitors as used in rheumatoid arthritis.Population based cohort study.Prospectively recorded data from national clinical, health, and demographic registers in Sweden 2001-10. Patients with rheumatoid arthritis treated (n = 10,878) or not (n = 42,198) with TNF inhibitors and matched general population comparators (n = 162,743).The primary outcome was first invasive melanoma in people without any history of invasive cancer of any type. Hazard ratios were estimated using Cox regression, comparing non-biological drug treated rheumatoid arthritis patients with the general population comparator and TNF inhibitor treated rheumatoid arthritis patients with those not treated with biological drugs. Secondary outcomes included in situ melanomas, second primary melanomas, and all site cancer.113 first invasive melanomas occurred in rheumatoid arthritis patients not treated with biological drugs, and 393 occurred in the general population comparator cohort. Rheumatoid arthritis patients not treated with biological drugs were not at significantly increased risk of melanoma compared with the general population (hazard ratio 1.2, 95% confidence interval 0.9 to 1.5). 38 first invasive melanomas occurred in rheumatoid arthritis patients treated with TNF inhibitors; these patients had an increased risk of melanoma compared with rheumatoid arthritis patients not treated with biological drugs (hazard ratio 1.5, 1.0 to 2.2; 20 additional cases per 100,000 person years). The risk of a second primary melanoma was non-significantly increased (hazard ratio 3.2, 0.8 to 13.1; n=3 v 10) in rheumatoid arthritis patients treated with TNF inhibitors compared with those not treated with biological drugs.Overall, patients with rheumatoid arthritis who have not been treated with biological drugs are not at increased risk of invasive melanoma compared with the general population. Rheumatoid arthritis patients selected for TNF inhibitor treatment are not at increased overall risk for cancer but have a 50% increased relative risk of invasive melanoma. Given the small increase in absolute risk, these finding may not markedly shift the overall risk-benefit balance of TNF inhibitors as used in clinical practice but might do so in patients at high risk of melanoma for other reasons.

  View details for DOI 10.1136/bmj.f1939

  View details for Web of Science ID 000317578300001

  View details for PubMedID 23568792

• Quadrivalent Human Papillomavirus Vaccine Effectiveness: A Swedish National Cohort Study JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Leval, A., Herweijer, E., Ploner, A., Eloranta, S., Simard, J. F., Dillner, J., Young, C., Netterlid, E., Sparen, P., Arnheim-Dahlstrom, L. 2013; 105 (7): 469-474

  Abstract

  Incidence of condyloma, or genital warts (GW), is the earliest possible disease outcome to measure when assessing the effectiveness of human papillomavirus (HPV) vaccination strategies. Efficacy trials that follow prespecified inclusion and exclusion criteria may not be fully generalizable to real-life HPV vaccination programs, which target a broader segment of the population. We assessed GW incidence after on-demand vaccination with quadrivalent HPV vaccine using individual-level data from the entire Swedish population.An open cohort of girls and women aged 10 to 44 years living in Sweden between 2006 and 2010 (N > 2.2 million) was linked to multiple population registers to identify incident GW in relation to HPV vaccination. For vaccine effectiveness, incidence rate ratios of GW were estimated using time-to-event analyses with adjustment for attained age and parental education level, stratifying on age at first vaccination.A total of 124 000 girls and women were vaccinated between 2006 and 2010. Girls and women with at least one university-educated parent were 15 times more likely to be vaccinated before age 20 years than girls and women whose parents did not complete high school (relative risk ratio = 15.45, 95% confidence interval [CI] = 14.65 to 16.30). Among those aged older than 20 years, GW rates declined among the unvaccinated, suggesting that HPV vaccines were preferentially used by women at high risk of GW. Vaccination effectiveness was 76% (95% CI = 73% to 79%) among those who received three doses of the vaccine with their first dose before age 20 years. Vaccine effectiveness was highest in girls vaccinated before age 14 years (effectiveness = 93%, 95% CI = 73% to 98%).Young age at first vaccination is imperative for maximizing quadrivalent HPV vaccine effectiveness.

  View details for DOI 10.1093/jnci/djt032

  View details for Web of Science ID 000317620500007

  View details for PubMedID 23486550

• Mortality Rates in Patients With Rheumatoid Arthritis Treated With Tumor Necrosis Factor Inhibitors Drug-Specific Comparisons in the Swedish Biologics Register ARTHRITIS AND RHEUMATISM Simard, J. F., Neovius, M., Askling, J. 2012; 64 (11): 3502-3510

  Abstract

  To determine whether the differences in the modes of action and safety profiles of individual tumor necrosis factor inhibitors (TNFi) translate into differential mortality risks, as investigated in etanercept, infliximab, and adalimumab.Data on patients with rheumatoid arthritis (RA) identified in the Swedish Biologics Register (Anti-Rheumatic Therapy in Sweden [ARTIS]) in whom first-ever treatment with a biologic agent (etanercept [n = 2,686], infliximab [n = 2,027], or adalimumab [n = 1,609]) was initiated between 2003 and 2008 were linked to national Swedish registers to get information on deaths from any cause, demographic features, RA characteristics, comorbid conditions, and concurrent treatment at the start of TNFi treatment. Hazard ratios (HRs) were modeled using multivariable adjusted and weighted Cox models.During 19,118 person-years of followup, 211 patients died (3.3%; 1.1 deaths per 100 person-years); 85% of the deaths occurred among patients who had been exposed to only one TNFi. We found no statistically significant difference in overall mortality rates across the exposure groups, regardless of adjustment and modeling approach (for infliximab versus etanercept, HR 1.1 [95% confidence interval (95% CI) 0.7-1.7], and for adalimumab versus etanercept, HR 1.3 [95% CI 0.9-2.0]).Overall, we noted no statistically significant difference in mortality rates between the 3 TNF inhibitors under study. Further studies need to examine whether certain subsets of patients are at increased risk of death with specific TNFi.

  View details for DOI 10.1002/art.34582

  View details for Web of Science ID 000310544500004

  View details for PubMedID 22886739

• Increased Risk of Systemic Lupus Erythematosus in 29,000 Patients with Biopsy-verified Celiac Disease JOURNAL OF RHEUMATOLOGY Ludvigsson, J. F., Rubio-tapia, A., Chowdhary, V., Murray, J. A., Simard, J. F. 2012; 39 (10): 1964-1970

  Abstract

  To investigate a possible association between celiac disease (CD) and systemic lupus erythematosus (SLE). Case series have indicated a possible association, but population-based studies are lacking.We compared the risk of SLE in 29,048 individuals with biopsy-verified CD (villous atrophy, Marsh 3) from Sweden's 28 pathology departments with that in 144,352 matched individuals from the general population identified through the Swedish Total Population Register. SLE was defined as having at least 2 records of SLE in the Swedish Patient Register. We used Cox regression to estimate hazard ratios (HR) for SLE.During followup, 54 individuals with CD had an incident SLE. This corresponded to an HR of 3.49 (95% CI 2.48-4.90), with an absolute risk of 17/100,000 person-years and an excess risk of 12/100,000. Beyond 5 years of followup, the HR for SLE was 2.54 (95% CI 1.57-4.10). While SLE was predominantly female, we found similar risk estimates in men and women. When we restricted our outcome to individuals who also had a dispensation for a medication used in SLE, the HR was 2.43 (95% CI 1.22-4.87). The HR for having 2 records of SLE diagnoses, out of which at least 1 had occurred in a department of rheumatology, nephrology/dialysis, internal medicine, or pediatrics, was 2.87 (95% CI 1.97-4.17).Individuals with CD were at a 3-fold increased risk of SLE compared to the general population. Although this excess risk remained more than 5 years after CD diagnosis, absolute risks were low.

  View details for DOI 10.3899/jrheum.120493

  View details for Web of Science ID 000310256100010

  View details for PubMedID 22859356

• Incidence of Genital Warts in Sweden Before and After Quadrivalent Human Papillomavirus Vaccine Availability JOURNAL OF INFECTIOUS DISEASES Leval, A., Herweijer, E., Arnheim-Dahlstrom, L., Walum, H., Frans, E., Sparen, P., Simard, J. F. 2012; 206 (6): 860-866

  Abstract

  More than 90% of genital warts (GW) cases are caused by human papillomavirus (HPV) types 6 and 11. The introduction of HPV vaccines necessitates the estimation of the population-based incidence of GW immediately before and after vaccination uptake.Incidence proportions were calculated using the entire population aged 10–44 years living in Sweden during 2006–2010. The Prescribed Drug Register and the National Patient Register were used to define GW episodes. Time trends were estimated using Poisson regression.In 2010, age-stratified incidence proportions of GW were highest for 20-year-old women (956 cases/100 000), while the incidence proportion among males was greatest at the slightly older age of 24 years (1137 cases/100 000). Crude rates were marginally higher among males than among females during 2006–2007 and appeared to later diverge. Between 2008 and 2010, the overall incidence appeared to increase among males, and the incidence among females declined. Females aged 17 and 18 years had a >25% decline in GW rates between 2006 and 2010, with significant decreases through the age of 25 years.This study provides a reasonable estimation of the incidence of GW in the Swedish population by use of register data, with results comparable to those from previous smaller studies. There was a downward trend of GW incidence among younger females between 2006 and 2010.

  View details for DOI 10.1093/infdis/jis405

  View details for Web of Science ID 000308233500010

  View details for PubMedID 22815381

• Rheumatoid factor positivity in the general population BRITISH MEDICAL JOURNAL Simard, J. F., Holmqvist, M. 2012; 345

  View details for DOI 10.1136/bmj.e5841

  View details for Web of Science ID 000308634100003

  View details for PubMedID 22956591

• Risk of ischaemic heart disease and cardiomyopathy in patients with haemochromatosis and in their first-degree relatives: a nationwide, population-based study JOURNAL OF INTERNAL MEDICINE Elmberg, M., Hultcrantz, R., Simard, J. F., Stal, P., Pehrsson, K., Askling, J. 2012; 272 (1): 45-54

  Abstract

  Iron-loaded macrophages increase atherosclerosis formation. Genetic haemochromatosis (GH) is an autosomal recessive disease characterized by iron overload, for example in the myocardium, but the reticuloendothelial system is depleted of iron. In contrast to the elevated risk of cardiomyopathy in GH, the risk of ischaemic heart disease (IHD) may therefore not be increased. Little is known of these risks among heterozygotes also being first-degree relatives (FDRs), thus sharing other factors for phenotypic expression of GH.To assess the risks of IHD and cardiomyopathy among haemochromatosis patients and their FDRs.Population-based cohort study.A total of 3531 haemochromatosis patients and 11 794 FDRs were identified using nationwide, population-based health and census registers. Matched (1:10) population controls were randomly selected. Individuals with a record of IHD and cardiomyopathy during 1997-2005 were identified through linkage with the National Patient Register. Relative risks were estimated using Cox proportional hazard regression.Of the 3531 patients, 259 were diagnosed with IHD compared with 3077 of the 37 369 controls [hazard ratio (HR) = 1.17; 95% CI, 1.03-1.33]. Based on 30 patients versus 115 controls, the HR for cardiomyopathy was 3.21 (95% CI, 2.15-4.81). Of 11 794 FDRs of haemochromatosis patients, 582 were registered with IHD compared with 6197 among FDRs of controls (HR = 1.05; 95% CI, 0.97-1.15). Based on 28 FDRs of patients versus 291 FDRs of controls registered with cardiomyopathy, the HR for cardiomyopathy was 1.06 (95% CI, 0.72-1.56).In patients with haemochromatosis, the increased risk of cardiomyopathy is much more pronounced than that of IHD, which is barely elevated. FDRs of haemochromatosis patients are not at increased risk of cardiomyopathy or IHD.

  View details for DOI 10.1111/j.1365-2796.2011.02475.x

  View details for Web of Science ID 000305510600005

  View details for PubMedID 22026548

• Is there a sex bias in prescribing anti-tumour necrosis factor medications to patients with rheumatoid arthritis? A nation-wide cross-sectional study ANNALS OF THE RHEUMATIC DISEASES Arkema, E. V., Neovius, M., Joelsson, J. K., Simard, J. F., Van Vollenhoven, R. F. 2012; 71 (7): 1203-1206

  Abstract

  To determine whether men and women with rheumatoid arthritis are prescribed anti-tumour necrosis factor (anti-TNF) treatment at different levels of disease activity.Data from the Swedish national biologics registry ARTIS were used to analyse characteristics of patients' disease at the start of the first anti-TNF treatment. Means for men and women were compared using t-tests, and non-normally distributed covariates were compared using the Wilcoxon rank-sum test. Linear regression models, adjusted for age and calendar year, were used to investigate the association between sex and each disease activity measurement.Women were younger and had longer disease duration at treatment start than men. Tender joint count, erythrocyte sedimentation rate, patient's global assessment, patient-reported pain and health assessment questionnaire scores were significantly higher in women, whereas men had a higher level of C-reactive protein (p<0.05 for all comparisons). Swollen joint count and physician's global assessment did not differ by sex.For women with rheumatoid arthritis, treatment with anti-TNF therapy was initiated at a higher level of subjective disease activity than for men, but at the same level of physician-reported disease activity. These data imply that patients' subjectively experienced disease activity may be discounted in the treatment decision.

  View details for DOI 10.1136/annrheumdis-2011-200947

  View details for Web of Science ID 000305293400016

  View details for PubMedID 22504565

• TNF-a Antagonist and Infection in Rheumatoid Arthritis. Open journal of rheumatology and autoimmune diseases Simard, J. F., Mittleman, M. A., Shadick, N. A., Karlson, E. W. 2012; 2 (2): 14-20

  Abstract

  Anti-TNF treatment may increase infection risk, although this has been difficult to study because the timing of anti-TNF treatment is driven by disease activity, which may influence infection susceptibility leading to confounding that varies over time. We evaluated the association between anti-TNF initiation in rheumatoid arthritis (RA) patients on disease modifying anti-rheumatic drugs (DMARD) and infection using multiple approaches adjusting for time-varying confounding.383 anti-TNF-naïve RA patients on ≥1 non-biologic-DMARD at enrollment from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) were followed up to two years. Pooled logistic regressions estimated the association between anti-TNF and infection by including time-varying covariates in the adjusted models and inverse probability treatment weighting (IPTW).Adjustment for time-varying disease activity and other suspected confounders yielded non-statistically significant positive associations between anti-TNF start and infection regardless of analytic approach (RRmvar_adj = 2.1, 95% CI: 0.8 - 5.8).Incorporating changing clinical status, and treatment indications and consequences, yielded consistently (though not significantly) elevated relative risks of infection associated with anti-TNF initiation. Due to limited statistical power, we cannot draw firm conclusions. However, we have illustrated multiple approaches adjusting for potential time-varying confounding in longitudinal studies and hope to replicate the approaches in larger studies.

  View details for PubMedID 25019035

• Treatment with tumor necrosis factor inhibitors and the risk of acute coronary syndromes in early rheumatoid arthritis ARTHRITIS AND RHEUMATISM Ljung, L., Simard, J. F., Jacobsson, L., Rantapaa-Dahlqvist, S., Askling, J. 2012; 64 (1): 42-52

  Abstract

  Rheumatoid arthritis (RA) is associated with an increased risk of ischemic heart disease, in both early and established RA. Data on the risk of ischemic heart disease in relation to therapy with tumor necrosis factor (TNF) antagonists (anti-TNF) are conflicting in patients with established RA and essentially lacking in those with early RA. In established RA, the risk of myocardial infarction has been linked to the response to anti-TNF therapies. The aim of this study was to determine the risk of acute coronary syndromes (ACS) in patients with early RA in relation to treatment with, and response to, anti-TNF.A cohort consisting of patients in whom RA was diagnosed between 1999 and 2007 was identified from the Swedish Rheumatology Register (n=6,000), from which information on disease activity and pharmacologic treatments was extracted. In a cohort study, the risk of first occurrence of an ACS was compared between patients treated with anti-TNF and those without exposure to anti-TNF, using hazard ratios (HRs). In a nested case-control study, the relationship between response to anti-TNF according to the European League Against Rheumatism (EULAR) response criteria and the risk of ACS was investigated.In the cohort study, treatment with anti-TNF was not related to any statistically significant alteration in the risk of ACS (HR 0.80, 95% confidence interval [95% CI] 0.52-1.24). In the nested case-control study, a good or moderate EULAR treatment response at 3 months and at 6 months was not associated with a risk of ACS (odds ratio [OR] 1.7, 95% CI 0.5-5.1 and OR 1.5, 95% CI 0.3-6.9, respectively), when adjusted for disease activity before treatment start.In this study of patients treated with anti-TNF within the first years of RA, neither treatment with, nor response to, anti-TNF therapy could be linked to any statistically significant decrease in the risk of ACS.

  View details for DOI 10.1002/art.30654

  View details for Web of Science ID 000298598100007

  View details for PubMedID 21898355

• Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study ARTHRITIS RESEARCH & THERAPY Gustafsson, J. T., Simard, J. F., Gunnarsson, I., Elvin, K., Lundberg, I. E., Hansson, L., Larsson, A., Svenungsson, E. 2012; 14 (2)

  Abstract

  Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and specifically cardiovascular (CVM) mortality in SLE, and to evaluate systematic coronary risk evaluation (SCORE).208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.During follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking among traditional risk factors, and high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.With the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.

  View details for DOI 10.1186/ar3759

  View details for Web of Science ID 000311025900005

  View details for PubMedID 22390680

• Time Trends in Risk and Risk Determinants of Non-Hodgkin Lymphoma in Solid Organ Transplant Recipients AMERICAN JOURNAL OF TRANSPLANTATION Fernberg, P., Edgren, G., Adami, J., Ingvar, A., Bellocco, R., Tufveson, G., Hoglund, P., Kinch, A., Simard, J. F., Baecklund, E., Lindelof, B., Pawitan, Y., Smedby, K. E. 2011; 11 (11): 2472-2482

  Abstract

  Organ transplantation increases risk of non-Hodgkin lymphoma (NHL), but long-term risk and time trends have seldom been evaluated. Immunosuppressive drug load is an important risk determinant, but the details are unclear. We studied NHL risk in a nationwide Swedish cohort of 11 081 graft recipients transplanted 1970-2008. Relative risks (RRs) were estimated within the cohort and versus the general population by age, sex, follow-up time and calendar period. NHL risk was also assessed by cumulative and average doses of immunosuppressive treatments in a nested case-control design throughout 1997 using conditional logistic regression. We observed 153 NHL cases during 97 853 years of follow-up. Compared with the general population, NHL risk was eightfold increased (RR 7.9; 95% confidence interval [CI] 6.6-9.4), and increased risks persisted after ≥15 years of follow-up among kidney (6.1; 95% CI 3.5-10) and nonkidney recipients (44; 14-103). Among nonkidney recipients, NHL risk was lower in the 2000s compared with the 1990s (0.5; 95% CI 0.3-1.0; p = 0.04). A high average dose of antithymocyte immunoglobulin (ATG) conferred an eightfold increased risk of NHL (OR 8.5; 95% CI 1.9-38). To conclude, posttransplant NHL risk decreased during the last decade among nonkidney recipients, possibly because of a more careful use of ATG, the introduction of new drugs, or both.

  View details for DOI 10.1111/j.1600-6143.2011.03704.x

  View details for Web of Science ID 000296335800024

  View details for PubMedID 21883909

• Sick leave and disability pension before and after initiation of antirheumatic therapies in clinical practice ANNALS OF THE RHEUMATIC DISEASES Neovius, M., Simard, J. F., Klareskog, L., Askling, J. 2011; 70 (8): 1407-1414

  Abstract

  To investigate sick leave and disability pension in rheumatoid arthritis (RA) in relation to the initiation of biological and non-biological antirheumatic therapies in clinical practice.Patients aged 19-60 years initiating non-biological mono (n=2796) or combination disease-modifying antirheumatic drug (DMARD) therapy (n=973), or biological agents (n=4787) were identified in the Swedish Rheumatology Quality Register between 1999 and 2007. Sick leave and disability pension data (1995-2010) were retrieved from national registers.During the year before the start of mono DMARD, combination DMARD and biological treatment, 10%, 12% and 43% of patients received disability pension benefits, respectively. The corresponding combined annual sick leave and disability pension days were 78 (54+25), 132 (105+27) and 190 (79+111). Irrespective of treatment type, initiators were characterised by a history of increasing sick leave and disability pension. Treatment start was associated with a break in this trajectory: sick leave decreased while disability pension increased, resulting in a net stabilisation of total days. Higher levels of days on sick leave and disability pension at treatment start were observed in patients initiating biologics in 1999 (236 days/year) compared with 2007 (150 days/year; p<0.001), but the trajectory thereafter remained largely similar and contrasted markedly with the level in the general population.Sick leave and disability pension increased rapidly before the initiation of antirheumatic therapy, which was associated with a halt but not a reversal of this development. Work ability is a metric of importance for clinical practice, signalling large remaining needs in the RA population, and the need for intervention earlier in the disease process.

  View details for DOI 10.1136/ard.2010.144139

  View details for Web of Science ID 000292188100011

  View details for PubMedID 21518724

• Does Cancer That Occurs During or After Anti-Tumor Necrosis Factor Therapy Have a Worse Prognosis? A National Assessment of Overall and Site-Specific Cancer Survival in Rheumatoid Arthritis Patients Treated With Biologic Agents ARTHRITIS AND RHEUMATISM Raaschou, P., Simard, J. F., Neovius, M., Askling, J. 2011; 63 (7): 1812-1822

  Abstract

  Tumor necrosis factor (TNF) may affect tumor development and spreading. While data on the incidence of cancer following anti-TNF therapy have been published, the purpose of this study was to examine the clinical presentation and outcome of cancers that develop during or after anti-TNF therapy.By linking data from Swedish clinical registries of rheumatoid arthritis (RA) patients, including Anti-Rheumatic Therapy in Sweden (ARTIS), the Swedish Biologics Register, with nationwide data on hospitalizations and outpatient visits for RA, we assembled a cohort of 78,483 RA patients who were alive in 1999 or who entered the cohort thereafter. Of these, 8,562 patients started therapy with a biologic agent (98% started an anti-TNF) during the period from January 1, 1999 to December 31, 2007. Linkage to the Swedish Cancer Register and other registers identified first primary cancers occurring during 1999-2007 as well as post-cancer survival through March 31, 2009. Through this linkage, we identified 314 cancers in patients who were undergoing, or had a history of, treatment with biologic agents and 4,650 cancers in patients who were biologics-naive at the time of cancer diagnosis. The distributions of tumor stage among the biologics-exposed and the biologics-naive patients were compared. The relative risk of death among the biologics-exposed versus the 586 matched biologics-naive cancer cases were assessed by Cox regression analyses. Through chart review in a defined subset, we gathered additional clinical information and validated the diagnoses.For all cancers combined, the distribution of cancer stages at the time of cancer diagnosis was largely similar between those in the biologics-exposed and the matched biologics-naive groups. Based on the total of 113 deaths among those with cancer in the biologics-exposed group versus the 256 deaths among those with cancer in the biologics-naive group, the relative risk of death following cancer associated with exposure to anti-TNF was 1.1 (95% confidence interval 0.8-1.6).During routine care, cancers that occur following anti-TNF therapy are not characterized by any markedly altered stage at presentation or by altered post-cancer survival rates.

  View details for DOI 10.1002/art.30247

  View details for Web of Science ID 000292809700009

  View details for PubMedID 21305513

• How large are the productivity losses in contemporary patients with RA, and how soon in relation to diagnosis do they develop? ANNALS OF THE RHEUMATIC DISEASES Neovius, M., Simard, J. F., Askling, J. 2011; 70 (6): 1010-1015

  Abstract

  To estimate the sick leave and disability pension trajectory in patients diagnosed with early rheumatoid arthritis (RA) 1999-2007, and in prevalent patients in 2007.Individuals aged 19-59 years diagnosed with early RA were identified in the Swedish Rheumatology Quality Register (1999-2007; n=3029; 47 years; 73% women). Additionally, prevalent patients in 2007 were identified in the National Patient Register (n=25,922; 52 years; 73% women). For each patient, five age-, sex-, education- and county-matched general population comparators were sampled. Sick leave and disability pension days were retrieved from national registers.Sick leave and disability pension increased from a mean 43 to 77 days/year from 2 to 1 years before RA diagnosis. A further increase to 147 days/year was observed the next year, followed by a rebound to 116 days/year 4 years after diagnosis. During the 4 years following diagnosis, sick leave decreased from a mean 118 to 35 and disability pension increased from 29 to 81 days/year. In the prevalent RA population, patients had a mean 158 annual days of sick leave and disability pension compared to 71 in comparators. Large variations existed across age, sex and education level, but RA patients had consistently higher levels. In 2007, the costs associated with sick leave and disability pension were €16,000 per patient with €9,000 attributable to RA.Despite better drugs and improved treatment strategies, data from contemporary patients with early and established RA continue to indicate large unmet needs.

  View details for DOI 10.1136/ard.2010.136812

  View details for Web of Science ID 000290149900021

  View details for PubMedID 21406455

• Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden ANNALS OF THE RHEUMATIC DISEASES Neovius, M., Simard, J. F., Askling, J. 2011; 70 (4): 624-629

  Abstract

  To provide Swedish nationwide data on the prevalence of rheumatoid arthritis (RA), including variations by age, sex, geography, demography and education level, and assess antirheumatic treatment penetration.Patients ≥16 years assigned an RA diagnosis were identified from inpatient (n=96 560; 1964-2007) and specialist outpatient care (n=56 336; 2001-2007) in the Swedish National Patient Register, and the Swedish Rheumatology Quality Register (n=21 242; 1995-2007). Data on prescriptions, demography, vital status and educational level were retrieved from national registers.A total of 58 102 individuals (mean age 66 years; 73% women) assigned an RA diagnosis were alive in Sweden in 2008, corresponding to a cumulative prevalence of 0.77% (women 1.11%, men 0.43%). The 2001-2007 period prevalence was 0.70%. Restriction to patients with ≥2 visits or diagnosis from a rheumatologist/internist reduced the overall cumulative prevalence to 0.68%. Whereas urban/rural differences (crude 0.65-1.00%) were explained by age differences, the age/sex-adjusted prevalence remained higher in patients with ≤9 years education (0.86%) than for those with 10-12 years (0.82%) and >12 years (0.65%). Treatment exposures (76% any disease-modifying antirheumatic drugs (DMARDs) or steroids, 64% any DMARD, 15% biological agents) varied with age; use of biological agents decreased from 22% in 16-59 years olds to 3% in ≥80 years olds. Any DMARD use correspondingly decreased from 71% to 43%. Applying age cut-off points from previous northern European and North American prevalence studies reduced or eliminated between-study differences.This nationwide approach yielded a prevalence of RA similar to previous regional assessments. While displaying only modest geographical variation and no urban/rural gradient, prevalence was associated with educational level. Although most patients received antirheumatic drugs, age was a strong treatment determinant.

  View details for DOI 10.1136/ard.2010.133371

  View details for Web of Science ID 000287965400011

  View details for PubMedID 21149495

• Generalisability of clinical registers used for drug safety and comparative effectiveness research: coverage of the Swedish Biologics Register ANNALS OF THE RHEUMATIC DISEASES Neovius, M., Simard, J. F., Sundstrom, A., Jacobsson, L., Geborek, P., Saxne, T., FELTELIUS, N., Klareskog, L., Askling, J. 2011; 70 (3): 516-519

  Abstract

  To determine coverage and generalisability of data in the Swedish Biologics Register ARTIS.Patients with adult onset rheumatoid arthritis (RA) were identified in the National Patient Register and the Swedish Rheumatology Quality Register, including the ARTIS cohort of patients exposed to biological agents. Exposure to etanercept and adalimumab between 2006 and 2008 was determined by register linkage to the Prescribed Drug Register which contains patient-level data on >99% of all etanercept and adalimumab use in Sweden.Of 62 897 patients with RA, 6510 had received treatment with etanercept or adalimumab according to the Prescribed Drug Register. Of these, 5673 were also registered in ARTIS, resulting in a national coverage of 87%. The regional variation was small with >85% coverage in 18 of 21 counties. In multivariable analysis, ARTIS-registered and non-registered patients did not differ by age (p=0.62), sex (p=0.84) or education level (p=0.24).Nationwide drug dispensing and demographic data may function as quality metrics for coverage and generalisability assessments. Using such data, the coverage of ARTIS was estimated at 87% with no indications of compromised external generalisability regarding demography.

  View details for DOI 10.1136/ard.2010.130914

  View details for Web of Science ID 000286927800019

  View details for PubMedID 21081525

• Ten years with biologics: to whom do data on effectiveness and safety apply? RHEUMATOLOGY Simard, J. F., Arkema, E. V., Sundstrom, A., Geborek, P., Saxne, T., Baecklund, E., Coster, L., Dackhammar, C., Jacobsson, L., Feltelius, N., Lindblad, S., Rantapaa-Dahlqvist, S., Klareskog, L., Van Vollenhoven, R. F., Neovius, M., Askling, J. 2011; 50 (1): 204-213

  Abstract

  During the past decade, the position of biologics in the therapeutic armamentarium, the number of approved indications and the number of available biologics have changed. Available data on (long-term) safety might thus pertain to patient populations not comparable with contemporary patients. The aim of this study was to assess the extent to which contemporary patients who start or switch biologic therapies are comparable with those patients who gave rise to the currently available data on effectiveness and safety.We identified all adult patients with RA (n=9612), PsA (n=1417) and other SpA (n=1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation.Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite <50% drug retention at 5 years, most patients remained exposed to some biologic.The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.

  View details for DOI 10.1093/rheumatology/keq326

  View details for Web of Science ID 000285193500028

  View details for PubMedID 21084326

• Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden AMERICAN JOURNAL OF TRANSPLANTATION Simard, J. F., Baecklund, E., Kinch, A., Brattstrom, C., Ingvar, A., Molin, D., Adami, J., Fernberge, P., Wilczek, H., Ekbom, A., Smedby, K. E. 2011; 11 (1): 146-151

  Abstract

  Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged <18 in Sweden between 1970-2007 (n = 536) in the National Patient Register and linked to the Cancer Register. Nationwide rates were used to calculate standardized incidence rate ratios and 95% CI estimating the association between transplant and cancer during maximum 36 years of follow-up. Nearly 7% of pediatric solid organ transplant recipients developed a premalignant or malignant tumor during follow-up. Transplantation was associated with an increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0-18.6): non-Hodgkin lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68-217), renal cell (n = 3, SIR = 105, 95% CI: 22-307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137-1934) and nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8-233.8). NHL typically appeared during childhood, while other tumors were diagnosed during adulthood. Apart from short-term attention toward the potential occurrence of NHL, our results suggest cancer surveillance into adulthood with special attention to skin, kidneys and the female genitalia.

  View details for DOI 10.1111/j.1600-6143.2010.03367.x

  View details for Web of Science ID 000285783500021

  View details for PubMedID 21199354

• Small-area variations in sales of TNF inhibitors in Sweden between 2000 and 2009 SCANDINAVIAN JOURNAL OF RHEUMATOLOGY Neovius, M., Sundstrom, A., Simard, J. F., Wettermark, B., Cars, T., FELTELIUS, N., Askling, J., Klareskog, L. 2011; 40 (1): 8-15

  Abstract

  To measure small-area variations in sales per capita of tumour necrosis factor (TNF) inhibitors.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.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).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.

  View details for DOI 10.3109/03009742.2010.493895

  View details for Web of Science ID 000287645500002

  View details for PubMedID 20955087

• Detection and evaluation of a drug safety signal concerning pancreatic cancer: lessons from a joint approach of three European biologics registers RHEUMATOLOGY Strangfeld, A., Hyrich, K., Askling, J., Arkema, E., Davies, R., Listing, J., Neovius, M., Simard, J., Symmons, D., Watson, K., Zink, A. 2011; 50 (1): 146-151

  Abstract

  A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the national biologics registers in the UK and Sweden was performed.Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers.Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden.The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.

  View details for DOI 10.1093/rheumatology/keq301

  View details for Web of Science ID 000285193500020

  View details for PubMedID 20861148

• Juvenile Idiopathic Arthritis and Risk of Cancer A Nationwide Cohort Study ARTHRITIS AND RHEUMATISM Simard, J. F., Neovius, M., Hagelberg, S., Askling, J. 2010; 62 (12): 3776-3782

  Abstract

  Reports of therapy-related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population.Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969-2007 and specialist outpatient visits in 2001-2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics-naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available.In this biologics-naive JIA cohort, 60 malignancies were observed during 131,144 person-years of followup, compared with 266 cancers observed during 661,758 person-years in the general population comparator (0.46 cases/1,000 person-years versus 0.40 cases/1,000 person-years; RR 1.1, 95% confidence interval [95% CI] 0.9-1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7-10.7) and cancers overall (RR 2.3, 95% CI 1.2-4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity.Although absolute risks were low, an elevated risk of malignancy was observed among biologics-naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies.

  View details for DOI 10.1002/art.27741

  View details for Web of Science ID 000285210200031

  View details for PubMedID 20827782

• Validity of self-report of infections in a longitudinal cohort of patients with rheumatoid arthritis differs by source of report and infection severity JOURNAL OF CLINICAL EPIDEMIOLOGY Simard, J. F., Stoll, M. L., Shadick, N. A., Karlson, E. W., Solomon, D. H. 2010; 63 (12): 1358-1362

  Abstract

  We evaluated and compared the validity of patients' and rheumatologists' reports of infection with those confirmed by medical record review.Reports of infections in 961 patients with rheumatoid arthritis from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) were included over a 2-year period. BRASS is a longitudinal prospective cohort that collects detailed questionnaire data from patients semiannually and their treating rheumatologists every year.Rheumatologist report of infection was more likely to be confirmed by medical record review than patient self-report (57.1% vs. 34.3% for definite or possible infections). Confirmation rates varied based on whether the participant received her primary care from the same network of health care providers. For participants with primary care "out of network," between 7.0% and 23.1% of patient or rheumatologist reports were confirmed by medical record review vs. between 16.1% and 41.7% for those with primary care "in network."The present study shows that relying strictly on patient or rheumatologist report of infection for a confirmed endpoint is not ideal but useful in case finding. The confirmation rate is affected by a number of factors including severity and definition of the infection and limited by data availability.

  View details for DOI 10.1016/j.jclinepi.2010.01.014

  View details for Web of Science ID 000284181800014

  View details for PubMedID 20430581

• A STAT4 risk allele is associated with ischaemic cerebrovascular events and anti-phospholipid antibodies in systemic lupus erythematosus ANNALS OF THE RHEUMATIC DISEASES Svenungsson, E., Gustafsson, J., Leonard, D., Sandling, J., Gunnarsson, I., Nordmark, G., Jonsen, A., Bengtsson, A. A., Sturfelt, G., Rantapaa-Dahlqvist, S., Elvin, K., Sundin, U., Garnier, S., Simard, J. F., Sigurdsson, S., Padyukov, L., Syvanen, A., Ronnblom, L. 2010; 69 (5): 834-840

  Abstract

  To investigate whether the risk allele for systemic lupus erythematosus (SLE) in the signal transducer and activator of transcription factor 4 (STAT4) gene, defined by the single nucleotide polymorphism (SNP) rs10181656(G), is associated with vascular events and/or presence of prothrombotic anti-phospholipid antibodies (aPL) in patients with SLE.Two independent groups of unrelated patients with SLE of Swedish ethnicity (n=424 and 154) were genotyped, and occurrence of previous manifestations of ischaemic heart disease (IHD), ischaemic cerebrovascular disease (ICVD) and venous thromboembolic events (VTE) was tabulated. aPL values were measured by ELISA. Matched controls (n=492 and 194) were genotyped.The STAT4 risk allele was more frequent in patients with SLE with previous arterial events (combined OR (OR(c))=1.5, 95% CI 1.1 to 2.0) compared to patients without such events. The association was mainly attributable to an accumulation of the risk allele among patients with ICVD (OR(c)=2.3, CI 1.6 to 3.3). There was no association with IHD or VTE. The presence of two or more aPLs was associated with the risk allele (OR(c)=1.6, 95% CI 1.2 to 2.0). In multivariable-adjusted logistic regression analyses treatment for hypertension, at least one STAT4 risk allele, older age, IgG anti-cardiolipin antibodies and longer SLE duration remained independently associated with previous ICVD (p

  View details for DOI 10.1136/ard.2009.115535

  View details for Web of Science ID 000276982300011

  View details for PubMedID 19762360

• Early Life Factors and Adult-onset Rheumatoid Arthritis JOURNAL OF RHEUMATOLOGY Simard, J. F., Costenbader, K. H., Hernan, M. A., Liang, M. H., Mittleman, M. A., Karlson, E. W. 2010; 37 (1): 32-37

  Abstract

  Early life factors have been associated with risk of developing autoimmune disease in adulthood. We investigated the association of preterm birth and being breastfed with the incidence of rheumatoid arthritis (RA) in 2 large prospective cohorts.We studied participants from the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII) who provided information on perinatal factors. The NHS (n = 121,701) and NHSII (n = 116,608) are large prospective cohorts of women followed since 1976 and 1989, respectively. Incident RA was confirmed using the American College of Rheumatology criteria and a medical record review. Cox models were used to estimate the hazard ratio of RA associated with being born preterm and being breastfed and its duration, adjusting for potential confounders. Random effects metaanalytic methods were used to compute combined estimates from the 2 cohorts.We found no statistically significant association between preterm birth and incident RA [relative risk (RR) = 1.1, 95% CI 0.8, 1.5]. Being breastfed was not associated with increased incidence of RA (RR = 1.0, 95% CI 0.7, 1.4), regardless of the duration of breastfeeding.In these cohorts of women, neither being preterm birth nor being breastfed was associated with the onset of RA.

  View details for DOI 10.3899/jrheum.090237

  View details for Web of Science ID 000273749900007

  View details for PubMedID 19833745

• TNF alpha Inhibitors May Improve Asthma Symptoms: A Case Series of 12 Patients With Rheumatoid Arthritis and Asthma JCR-JOURNAL OF CLINICAL RHEUMATOLOGY Stoll, M. L., Solomon, D. H., Batra, K. L., Simard, J. F., Karlson, E. W., Dellaripa, P. F., Weinblatt, M. E., Glass, R., Shadick, N. A. 2009; 15 (4): 198-200

  View details for DOI 10.1097/RHU.0b013e3181a7ace9

  View details for Web of Science ID 000266735700011

  View details for PubMedID 19455057

• Is birthweight associated with risk of rheumatoid arthritis? Data from a large cohort study ANNALS OF THE RHEUMATIC DISEASES Mandl, L. A., Costenbader, K. H., Simard, J. F., Karlson, E. W. 2009; 68 (4): 514-518

  Abstract

  The "fetal origins of adult disease" hypothesis suggests the uterine environment can influence the susceptibility of a fetus to future disease. We examine whether the fetal environment, as reflected by birthweight, could modulate an individual's future risk of rheumatoid arthritis (RA).The relationship between birthweight and the risk of incident RA was studied in 87 077 women followed prospectively in the Nurses' Health Study cohort. New cases of RA diagnosed between 1976 and 2002 were confirmed in 619 women. The association between birthweight and the future development of RA was studied in age-adjusted and Cox proportional hazard models adjusting for age and potential confounders, including history of maternal diabetes, childhood socioeconomic status, prematurity, maternal and paternal smoking, as well as additionally adjusting for risk factors for RA including smoking, age at menarche, use of oral contraceptives, use of post-menopausal hormones, total lifetime breastfeeding, and body mass index (BMI) at age 18.In an age-adjusted model, birthweight >4.54 kg vs birthweight 3.2-3.85 kg was associated with a two-fold increased risk of RA (relative risk (RR) = 2.1, 95% CI 1.4 to 3.3). Further adjusting for potential confounders and risk factors did not change this relationship (RR = 2.0, 95% CI 1.3 to 3.0). Findings were similar when we limited cases to those with rheumatoid factor positive RA (RR = 2.1, 95% CI = 1.2 to 3.6).In this large prospective cohort, birthweight >4.54 kg was associated with a two-fold increased risk of adult onset RA, compared with those of average birthweight. Further study of this observation may provide insight into the pathogenesis of RA.

  View details for DOI 10.1136/ard.2007.080937

  View details for Web of Science ID 000264196000011

  View details for PubMedID 18593757

• Exposure to maternal smoking and incident SLE in a prospective cohort study LUPUS Simard, J. F., Costenbader, K. H., Liang, M. H., Karlson, E. W., Mittleman, M. A. 2009; 18 (5): 431-435

  Abstract

  Current cigarette smoking is a risk factor for SLE, and recent work has demonstrated that early-life smoke exposure was related to the risk of related rheumatic conditions in female children. Therefore, we sought to investigate whether early-life cigarette smoke exposure might be associated with incidence of SLE in adult women. We studied 93,054 Nurses' Health Study (NHS) and 95,554 NHSII participants free of SLE at baseline who provided information on perinatal exposures. By medical record review, 236 incident SLE cases were confirmed (142 NHS and 94 NHSII) among these women using American College of Rheumatology criteria. We used stratified Cox models to estimate the association of smoke exposure with SLE adjusting for race, birth weight, preterm birth and parents' occupation. Combined estimates were computed using random effects meta-analytic techniques. Maternal cigarette smoking did not increase the risk of SLE (relative risk (RR) = 0.9, 95%CI: 0.6 to 1.4) nor did paternal smoking during the participant's childhood (RR = 1.0, 95% CI: 0.8 to 1.3) in combined analyses. Early-life exposure to cigarette smoke due to mothers' or fathers' smoking was not associated with increased risk of adult-onset SLE in women.

  View details for DOI 10.1177/0961203308098186

  View details for Web of Science ID 000265552000009

  View details for PubMedID 19318396

• Methodologic issues in the validation of putative biomarkers and surrogate endpoints in treatment evaluation for systemic lupus erythematosus. Endocrine, metabolic & immune disorders drug targets Liang, M. H., Simard, J. F., Costenbader, K., Dore, B. T., Ward, M., Fortin, P. R., Illei, G. G., Manzi, S., Mittleman, B., Buyon, J., Gupta, S., Abrahamowicz, M. 2009; 9 (1): 108-112

  Abstract

  No new drugs have been approved for the treatment of systemic lupus erythematosus (SLE) by the Food and Drug Administration for the last 30 years. One barrier has been the lack of validated biomarkers and surrogate endpoints. Validation of SLE biomarkers in the past have been methodologically flawed. We put forth a conceptual framework and five critical criterion for validating putative biomarkers and bio-surrogates in this heterogeneous multi-system disease with protean manifestations. Using the example of a putative biomarker for end-stage lupus nephritis, we performed computer simulations for planning a biomarker bio-repository to support the validation process. "Random time window" sampling where a biomarker is obtained in an interval randomly selected from the total follow-up time for that subject creates survival bias. This can be avoided by the "fixed calendar window" design, in which biomarkers are measured within the same, pre-specified period for all cohort members who remain at risk during that period. In lupus nephritis where the incidence rate of end-stage renal disease is relatively low, to accumulate 300 instances of end-stage renal disease, at risk patients would have to be followed for about 5,000 person-years, implying 500 subjects followed, on average, for about 10 years. Increasing the number of biomarker determinations per subject from one to five reduces the required number of subjects by 10-15%, while further increases in the number of observations per subject yielded much smaller gains. The large numbers of subjects required for a bio-repository, makes it essential to maximize the efficiency of study designs and analyses and provides the strongest rationale for collaboration and the use of standardized measures to ensure comparability.

  View details for PubMedID 19275685

• Predictors of the first cardiovascular event in patients with systemic lupus erythematosus - a prospective cohort study ARTHRITIS RESEARCH & THERAPY Gustafsson, J., Gunnarsson, I., Borjesson, O., Pettersson, S., Moller, S., Fei, G., Elvin, K., Simard, J. F., Hansson, L., Lundberg, I. E., Larsson, A., Svenungsson, E. 2009; 11 (6)

  Abstract

  Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.

  View details for DOI 10.1186/ar2878

  View details for Web of Science ID 000278282100026

  View details for PubMedID 20003285

• Perinatal factors and adult-onset lupus 40th Annual Meeting of the Society-for-Epidemiologic-Research Simard, J. F., Karlson, E. W., Costenbader, K. H., Hernan, M. A., Stampfer, M. J., Liang, M. H., Mittleman, M. A. WILEY-LISS. 2008: 1155–61

  Abstract

  Some evidence suggests that perinatal factors, including birth weight and breastfeeding, may influence the occurrence of autoimmune rheumatic diseases. However, few studies have investigated these factors in patients with systemic lupus erythematosus (SLE). Therefore, we evaluated the role of birth weight, being breastfed, and preterm birth on the incidence of SLE in participants in the Nurses' Health Study (NHS) and the Nurses' Health Study II (NHSII).We studied 87,411 NHS participants and 98,413 NHSII participants without SLE at baseline who provided information on perinatal exposures. Among these women, during 26 (NHS) and 14 (NHSII) years of followup, 222 incident SLE cases were confirmed (136 NHS and 86 NHSII) by medical record review using American College of Rheumatology criteria. We used stratified Cox models to estimate the association of perinatal factors with SLE, adjusting for race, early passive cigarette smoke exposure, and parents' occupation. A random-effects meta-analysis was used to compute combined estimates across the 2 cohorts.After adjustment for multiple potential confounders, high birth weight (> or =10 pounds) was associated with increased rates of SLE compared with normal birth weight (7-8.5 pounds; rate ratio [RR] 2.7, 95% confidence interval [95% CI] 1.2-5.9), as was being born > or =2 weeks preterm (RR 1.9, 95% CI 1.2-3.0); however, being breastfed was not (RR 0.8, 95% CI 0.6-1.1).Birth weight > or =10 pounds and preterm birth were both positively associated with incident SLE among women.

  View details for DOI 10.1002/art.23930

  View details for Web of Science ID 000258888800014

  View details for PubMedID 18668600

• Exposure to cigarette smoke in utero - Comparison of reports from mother and daughter EPIDEMIOLOGY Simard, J. F., Rosner, B. A., Michels, K. B. 2008; 19 (4): 628-633

  Abstract

  Smoking during pregnancy has been associated with asthma, obesity, and decreased cognitive functioning in the offspring. To study the role of in utero smoking exposure in offsprings' adult health outcomes, it may be necessary to rely upon reports by the offspring themselves.We studied 34,949 mother-daughter pairs participating in the Nurses' Health Study II for whom data on the daughter's early passive cigarette smoke exposure had been obtained from both mother and daughter. We calculated sensitivity and specificity of daughter's early exposure to smoke (using mother's report as the gold standard), as well as kappa statistics. Mother and daughter reports were also analyzed as risk factors for asthma and birthweight to demonstrate face validity.Sensitivity of daughters' reported prenatal exposure ranged from 74% to 85%, while specificity was between 90% and 95% (kappa = 0.72-0.81). Daughter's reported childhood exposure as a proxy for mother's report of smoking during pregnancy had a sensitivity of 89% and specificity of 88%. Results were similar for daughter's report of father's smoking during her childhood. Maternal smoking during pregnancy is consistently associated with reductions in offspring birthweight, and with asthma risk in offspring. The daughter's risk of being very low (<1500 g) or low birthweight (<2500 g) or of having asthma were similar when exposure was defined according to mother's report, daughter's report of fetal smoke exposure, and daughter's report of mother's smoking during childhood.Daughter's report of mother's smoking prenatally and in childhood are good proxy measures for mother's own report of smoking during pregnancy.

  View details for DOI 10.1097/EDE.0b013e3181761cdb

  View details for Web of Science ID 000256865100020

  View details for PubMedID 18467961

• What can epidemiology tell us about systemic lupus erythematosus? INTERNATIONAL JOURNAL OF CLINICAL PRACTICE Simard, J. F., Costenbader, K. H. 2007; 61 (7): 1170-1180

  Abstract

  Systemic lupus erythematosus (SLE) is an often-severe autoimmune rheumatic disease most commonly diagnosed in women in their childbearing years. It is thought to develop when genetically predisposed individuals are exposed to one or more environmental triggers. This review outlines the epidemiologic evidence for several putative risk factors including cigarette smoke, hormonal and reproductive factors, environmental silica and infectious exposures, as well as many yet to be identified. We also review the evidence for factors associated with increased disease activity and adverse outcomes in SLE. We review the literature on the epidemiology of SLE, its distribution, potential risk factors for its onset and for adverse outcomes. The information considered in this review was gathered through extensive review of the literature. Online Pubmed literature searches, previous reviews of the epidemiology of SLE and original studies were employed. Epidemiologic studies have helped to identify some of these potential risk factors, including exogenous hormone use, cigarette smoking, infections such as Epstein-Barr virus (EBV) and crystalline silica exposure, but many more have yet to be studied. These exposures may interact with multiple genetic factors in determining susceptibility to SLE. While epidemiologic research has contributed an enormous amount to our understanding of the disease and its pathogenesis, there are many more avenues of epidemiologic research that deserve to be pursued.

  View details for DOI 10.1111/j.1742-1241.2007.01434.x

  View details for Web of Science ID 000247319600019

  View details for PubMedID 17577298

• Prevalent rheumatoid arthritis and diabetes among NHANES III participants aged 60 and older JOURNAL OF RHEUMATOLOGY Simard, J. F., Mittleman, M. A. 2007; 34 (3): 469-473

  Abstract

  This study examines the cross-sectional association between prevalent rheumatoid arthritis (RA) and diabetes among noninstitutionalized US civilians aged >or= 60 years between 1988 and 1994.Using National Health and Nutrition Examination Survey III data from the National Center for Health Statistics, RA and diabetes were identified using several classification schemes. In total, 5302 survey participants aged >or= 60 years were included in logistic regression analyses taking survey weights into account. We also conducted sensitivity analyses restricting the study population to participants not recently prescribed glucocorticoids and fasting at least 8 hours prior to blood draw, as well as data incorporated from the Multiple Imputation Project.Among the 5302 participants aged >or= 60, 144 participants had RA and 24 of these also were found to have prevalent diabetes. The adjusted odds ratios for the cross-sectional association between RA and diabetes ranged from 1.1 to 1.5, but did not reach statistical significance.While this study cannot definitively rule out a modest non-null association, we can conclude that there is no evidence of a strong cross-sectional association between prevalent RA and diabetes in subjects aged >or= 60 years. Future longitudinal studies with more participants with RA are required to further evaluate a possible association between RA and the incidence of diabetes.

  View details for Web of Science ID 000244613800006

  View details for PubMedID 17183622

• The large print giveth and the small print taketh away: Preemptive treatment of serologically active, clinically quiet systemic lupus erythematosus ARTHRITIS AND RHEUMATISM Liang, M. H., Simard, J. F. 2006; 54 (11): 3378-3380

  View details for DOI 10.1002/art.22199

  View details for Web of Science ID 000241981800002

  View details for PubMedID 17075813

• Evidence for differential acquired drug resistance to anti-tumour necrosis factor agents in rheumatoid arthritis ANNALS OF THE RHEUMATIC DISEASES Finckh, A., Simard, J. F., Gabay, C., Guerne, P. 2006; 65 (6): 746-752

  Abstract

  Acquired drug resistance or gradual drug failure has been described with most disease modifying antirheumatic drugs (DMARDs) and is also starting to be recognised with anti-tumour necrosis factor (anti-TNF) agents.To study acquired drug resistance to anti-TNF agents in rheumatoid arthritis (RA).Swiss health authorities requested continuous monitoring of patients receiving biological agents. Intensification of co-therapy with traditional DMARDs, gradual dose escalation, and drug discontinuation rates in all patients receiving infliximab, etanercept, or adalimumab, adjusting for potential confounders, were analysed. Intensification of DMARD co-therapy and time to discontinuation of the three anti-TNF agents were analysed using a proportional hazards models. Dose escalation and evolution of RA disease activity (DAS28) were analysed using a longitudinal regression model.1198 patients contributing 1450 patient-years of anti-TNF treatment met the inclusion criteria. The rate of intensification of traditional DMARD co-therapy over time was significantly higher with infliximab (hazards ratio = 1.73 (99% confidence interval (CI) 1.19 to 2.51)) than with the two other agents. Infliximab also showed significant dose escalation over time, with an average dose increase of +12% (99% CI 8% to 16%) after 1 year, and +18% (99% CI 11% to 25%) after 2 years. No significant differences in discontinuation rates were seen between the three anti-TNF agents (ANOVA, p = 0.67). Evolution of disease activity over time indicated a lower therapeutic response to infliximab (DAS28, p<0.001) compared with etanercept, after 6 months' treatment.In this population, infliximab was associated with a higher risk of requiring intensification of DMARD co-therapy than the other anti-TNF agents and a significant dose escalation over time. Analysis of RA disease activity indicated a reduced therapeutic response to infliximab after the first 6 months of treatment, suggestive of acquired drug resistance.

  View details for DOI 10.1136/ard.2005.045062

  View details for Web of Science ID 000237513300009

  View details for PubMedID 16339288

• The effectiveness of anti-tumor necrosis factor therapy in preventing progressive radiographic joint damage in rheumatoid arthritis - A population-based study ARTHRITIS AND RHEUMATISM Finckh, A., Simard, J. F., Duryea, J., Liang, M. H., Huang, J., Daneel, S., Forster, A., Gabay, C., Guerne, P. A. 2006; 54 (1): 54-59

  Abstract

  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.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.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).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.

  View details for Web of Science ID 000234605200008

  View details for PubMedID 16385495