Addressing the research gap: access to care hinders genetic discovery in systemic lupus erythematosus patients throughout the African diaspora.

Systemic lupus erythematosus (SLE) is a complex autoimmune condition that disproportionately impacts non-White ethnic and racial groups, particularly individuals in the African diaspora who experience heightened incidence, prevalence, and adverse outcomes. Genetic and epigenetic factors play significant roles in SLE risk, however these factors neither explain the whole of SLE risk nor the stark racial disparities we observe. Moreover, our understanding of genetic risk factors within African ancestry populations is limited due to social and environmental influences on research participation, disease presentation, and healthcare access. Globally, the African diaspora faces barriers in accessing essential SLE diagnostic tools, therapeutics, healthcare practitioners, and high-quality clinical and translational research studies. Here, we provide insights into the current state of genetic studies within African ancestry populations and highlight the unique challenges encountered in SLE care and research across countries of varying income levels. We also identify opportunities to address these disparities and promote scientific equity for individuals affected by SLE within the global African diaspora.

Misdiagnosis, Missed Diagnosis, and Delayed Diagnosis of Lupus: A Qualitative Study of Rheumatologists.

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

Annual trends in pain management modalities in patients with newly diagnosed autoimmune rheumatic diseases in the USA from 2007 to 2021: an administrative claims-based study.

BACKGROUND: Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine annual trends in pain management modalities among patients with autoimmune rheumatic diseases. METHODS: We identified newly diagnosed patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, or systemic lupus erythematosus (SLE) in the Merative Marketscan Research Databases from 2007 to 2021. The database includes deidentified inpatient and outpatient health encounters with employment-sponsored health insurance claims in the USA. We found minimal occurrences of multiple overlapping conditions and included only the initial recorded diagnosis for each patient. We determined the annual incidence of patients treated with opioids, anticonvulsants, antidepressants, skeletal muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, and physical therapy in the year following diagnosis. Logistic regression was used to estimate the association between calendar year and outcomes, adjusted for age, sex, and region. FINDINGS: We included 141 962 patients: 10 927 with ankylosing spondylitis, 21 438 with psoriatic arthritis, 71 393 with rheumatoid arthritis, 16 718 with Sjögren's syndrome, 18 018 with SLE, and 3468 with systemic sclerosis. 107 475 (75·7%) were women and 34 487 (24·3%) were men. Overall, the incidence of opioid use increased annually until 2014 by 4% (adjusted odds ratio [aOR] 1·04 [95% CI 1·03-1·04]) and decreased annually by 15% after 2014 (0·85 [0·84-0·86]). The incidence of physical therapy use increased annually by 5% until 2014 (aOR 1·05 [95% CI 1·04-1·06]), with a slight decrease annually by 1% after 2014 (0·99 [0·98-1·00]). The incidence of anticonvulsant use increased annually by 7% until 2014 (aOR 1·07 [95% CI 1·07-1·08]) and did not significantly change after 2014 (1·00 [0·99-1·00]). Before 2014, the incidence of NSAIDs use increased by 2% annually (aOR 1·02 [95% CI 1·02-1·03]); however, after 2014, the incidence decreased annually by 5% (0·95 [0·95-0·96]). These trends did not differ by sex except for NSAID use before 2014 (pinteraction=0·02) and topical analgesic use after 2014 (pinteraction=0·0100). INTERPRETATION: Since 2014, the use of non-opioid pain management modalities has increased or stabilised, whereas opioid and NSAID use has declined. Future studies are needed to evaluate the effectiveness of these changes, and the effects they have had on outcomes such as quality of life, disability, and function. FUNDING: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Impact of Incentives on Physician Participation in Research Surveys: Randomized Experiment.

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

The Problem of Pain in Lupus: Epidemiological Profiles of Patients Attending Multidisciplinary Pain Clinics.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) bear a significant burden of pain. We aimed to identify factors that distinguish patients with SLE referred to comprehensive pain clinics and those who are not. Characterizing this patient population will identify unmet needs in SLE management and inform efforts to improve pain care in rheumatology. METHODS: Among patients with SLE with ≥2 rheumatology clinic visits in a large hospital system from 1998 to 2023 (n = 1319), we examined factors that distinguished those who had at least one visit to multidisciplinary pain clinics (n = 77, 5.8%) from those who did not have any visits (n = 1242, 94.2%) with a focus on biopsychosocial and socioeconomic characteristics. We extracted demographic data and ICD-9/ICD-10 codes from the EHR. RESULTS: Patients with SLE attending the pain clinics exhibited characteristics including average older age (mean age ± SD: 54.1 ± 17.9 vs. 48.4 ± 19.9), a higher likelihood of relying on public health insurance (50.7% vs. 34.2%), and a greater representation of Black patients (9.1% vs. 4.4%) compared to SLE patients not seen in pain clinics. Nearly all patients seen at the pain clinics presented with at least one chronic overlapping pain condition (96.1% vs. 58.6%), demonstrated a higher likelihood of having a mental health diagnosis (76.7% vs. 42.4%), and exhibited a greater number of comorbidities (mean ± SD: 6.0 ± 3.0 vs. 2.9 ± 2.6) compared to those not attending the pain clinic. CONCLUSION: We found notable sociodemographic and clinical differences between these patient populations. Patients presenting with multiple comorbidities might benefit from further pain screening and referral to pain clinics to provide comprehensive care, and earlier referral could mitigate the development and progression of multimorbidities.

Trends in Patient Representation in Low Back Pain Pharmacological Randomized Clinical Trials, 2011 to 2020: A Systematic Review.

Low back pain (LBP) significantly affects global health, with associated detrimental outcomes such as physical impairment, emotional distress, and exacerbated mental health symptoms. This study evaluated the representation of marginalized groups, including racialized, gender minority, pregnant/lactating, and elderly individuals in randomized controlled trials for pharmacological interventions treating LBP from 2011 to 2020. We searched Embase, MEDLINE, and CINAHL in December 2021, and 139 studies were eligible. Most trials (n = 113, 81%) reported participant sex; however, no study collected data on sexual and gender minorities, and the majority (n = 99, 71%) excluded pregnant/lactating individuals. Most trials (n = 105, 76%) reported no data on participant race or ethnicity. We limited within-country analyses of race and ethnicity to US-based trials because US-based trials were more likely to report race and/or ethnicity (48%) compared to non-US-based trials (8%). Black participants were the only racialized group whose composition was comparable to US Census estimates. About half (n = 73, 53%) of all trials had an upper age limit for eligibility (range: 40-85 years old) and 24% (n = 33) excluded adults aged >65 years. Our findings confirm that trials for pharmacological LBP interventions underreport demographic data, and the trials that include this data have unrepresentative samples. There is an urgent need for more inclusive and representative patient samples to ensure generalizability and equitable benefits. Standardizing demographic data reporting and integrating community-based participatory research methods can help foster inclusive research practices. This review was registered with prospective register of systematic reviews (PROSPERO), ID 296017. PERSPECTIVE: This systematic review investigates patient representation in pharmacological-based clinical trials for low back pain, LBP, the most prevalent pain condition worldwide. Improvements in reporting demographic data and recruiting diverse participant populations-across different racialized, gender and sexual minority, and age groups-will help clinical research generalizability and provide equitable benefits.

The Problem of Pain in Rheumatology: Variations in Case Definitions Derived From Chronic Pain Phenotyping Algorithms Using Electronic Health Records.

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

Biologics Initiation in Rheumatoid Arthritis by Race and Ethnicity: Results From a Randomized Survey Study.

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

The global epidemiology of SLE: narrowing the knowledge gaps.

SLE is a global health concern that unevenly affects certain ethnic/racial groups. Individuals of Asian, Black, Hispanic and Indigenous ethnicity/race are amongst those who experience increased prevalence, incidence, morbidity and mortality. Population-based surveillance studies from many regions are few and often still in nascent stages. Many of these areas are challenged by restricted access to diagnostics and therapeutics. Without accurately capturing the worldwide burden and distribution of SLE, appropriately dedicating resources to improve global SLE outcomes may be challenging. This review discusses recent SLE epidemiological studies, highlighting the challenges and emerging opportunities in low- and middle-income countries. We suggest means of closing these gaps to better address the global health need in SLE.

The Problem of Pain in the United States: A Population-Based Characterization of Biopsychosocial Correlates of High Impact Chronic Pain Using the National Health Interview Survey.

Over 20 million adults in the United States live with high impact chronic pain (HICP), or chronic pain that limits life or work activities for ≥3 months. It is critically important to differentiate people with HICP from those who sustain normal activities although experiencing chronic pain. Therefore, we aim to help clinicians and researchers identify those with HICP by: 1) developing models that identify factors associated with HICP using the 2016 national health interview survey (NHIS) and 2) evaluating the performances of those models overall and by sociodemographic subgroups (sex, age, and race/ethnicity). Our analysis included 32,980 respondents. We fitted logistic regression models with LASSO (a parametric model) and random forest (a nonparametric model) for predicting HICP using the whole sample. Both models performed well. The most important factors associated with HICP were those related to underlying ill-health (arthritis and rheumatism, hospitalizations, and emergency department visits) and poor psychological well-being. These factors can be used for identifying higher-risk sub-groups for screening for HICP. We will externally validate these findings in future work. We need future studies that longitudinally predict the initiation and maintenance of HICP, then use this information to prevent HICP and direct patients to optimal treatments. PERSPECTIVE: Our study developed models to identify factors associated with high-impact chronic pain (HICP) using the 2016 National Health Interview Survey. There was homogeneity in the factors associated with HICP by gender, age, and race/ethnicity. Understanding these risk factors is crucial to support the identification of populations and individuals at highest risk for developing HICP and improve access to interventions that target these high-risk subgroups.

Risk of End-Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study.

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

Factors Associated With the Initiation and Retention of Patients With Lupus in the Chronic Disease Self-Management Program.

OBJECTIVE: The Chronic Disease Self-Management Program (CDSMP) is designed to enhance patients' self-efficacy and skills to manage their chronic illness. There is compelling evidence for the benefits of the CDSMP among patients with systemic lupus erythematosus (SLE); however, little is known about predictors of participation among Black women with SLE. We examined factors associated with CDSMP initiation and completion in this population. METHODS: We studied 228 Black women with SLE who consented to attend a CDSMP workshop. We used logistic regression to calculate unadjusted and adjusted odds ratios (ORs) for being a CDSMP initiator (a participant registered into the CDSMP who attended at least 1 of the first 2 weekly classes) and a CDSMP completer (a participant who completed at least 4 of 6 weekly classes). RESULTS: The majority of participants were CDSMP initiators (74% [n = 168]). Of those, 126 (75%) were CDSMP completers. Older age (adjusted OR [ORadj ] 1.03 [95% confidence interval (95% CI) 1.00-1.06]) and unemployment/disability (ORadj 2.05 [95% CI 1.05-4.14]) increased the odds of being a CDSMP initiator. The odds of initiating the CDSMP decreased by 22% for each additional child in the household (OR 0.78 [95% CI 0.62-0.98]), but this association became nonsignificant in the adjusted model (ORadj 0.89 [95% CI 0.68-1.18]). The only factor that differed significantly between CDSMP completers and noncompleters was age, with 4% higher odds of being a completer for each additional year of age (ORadj 1.04 [95% CI 1.00-1.07]). CONCLUSION: Our findings suggest that young Black women with SLE face barriers to attend and complete in-person CDSMP workshops, possibly in relation to work and child care demands.

The Problem of Pain in Rheumatology: Clinical Profiles Associated With Concomitant Diagnoses With Chronic Overlapping Pain Conditions.

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

A Review of Potential National Chronic Pain Surveillance Systems in the United States.

Pain has been established as a major public health problem in the United States (U.S.) with 50 million adults experiencing chronic pain and 20 million afflicted with high-impact chronic pain (ie, chronic pain that interferes with life or work activities). High financial and social costs are associated with chronic pain. Over the past 2 decades, pain management has been complicated by the marked increase in opioids prescribed to treat chronic noncancer pain and by the concurrent opioid crisis. Monitoring the prevalence of chronic pain and pain management is especially important because pain management is changing in uncertain ways. We review potential U.S. chronic pain surveillance systems, present potential difficulties of chronic pain surveillance, and explore how to address chronic pain surveillance in the current opioid era. We consider case definitions, severity, anatomic site, and varieties of chronic pain management strategies in reviewing and evaluating national surveys for chronic pain surveillance. Based on the criteria evaluated, the National Health Interview Survey offers the best single source for pain surveillance as the pain-related questions administered are brief, valid, and cover a broad scope of pain-related phenomena. PERSPECTIVE: This review article describes data sources that can be leveraged to conduct national chronic pain surveillance in the United States, explores case defining or pain-related questions administered, and evaluates them against 8 surveillance attributes.

Global epidemiology of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations that predominantly affects young women. Certain ethnic groups are more vulnerable than others to developing SLE and experience increased morbidity and mortality. Reports of the global incidence and prevalence of SLE vary widely, owing to inherent variation in population demographics, environmental exposures and socioeconomic factors. Differences in study design and case definitions also contribute to inconsistent reporting. Very little is known about the incidence of SLE in Africa and Australasia. Identifying and remediating such gaps in epidemiology is critical to understanding the global burden of SLE and improving patient outcomes. Mortality from SLE is still two to three times higher than that of the general population. Internationally, the frequent causes of death for patients with SLE include infection and cardiovascular disease. Even without new therapies, mortality can potentially be mitigated with enhanced quality of care. This Review focuses primarily on the past 5 years of global epidemiological studies and discusses the regional incidence and prevalence of SLE and top causes of mortality.

Evidence of under-reporting of early-onset preeclampsia using register data.

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 ≥34 weeks) 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.

The Problem of Pain in Systemic Lupus Erythematosus: An Explication of the Role of Biopsychosocial Mechanisms.

OBJECTIVE: To define biopsychosocial mechanisms of pain that go above and beyond disease activity and organ damage in systemic lupus erythematosus (SLE). METHODS: We conducted a cross-sectional analysis of patient-reported data in a population-based registry of 766 people with SLE. Predictors of pain intensity and interference were examined using hierarchical linear regression. We built 2 main hierarchical regression models with pain intensity and interference as outcomes, both regressed on disease activity and organ damage. For each model, we sought to establish the relationship between pain outcomes and the primary exposures using sequential steps comprising the inclusion of each construct in 6 stages: demographic, socioeconomic, physical, psychological, behavioral, and social factors. We also conducted sensitivity analyses eliminating all overt aspects of pain in the disease activity measure and reestimated the models. RESULTS: Disease activity and organ damage explained 32-33% of the variance in pain intensity and interference. Sociodemographic factors accounted for an additional 4-9% of variance in pain outcomes, whereas psychosocial/behavioral factors accounted for the final 4% of variance. In the sensitivity analyses, we found that disease activity and organ damage explained 25% of the variance in pain outcomes. CONCLUSION: Disease activity only explained 33% of the variance in pain outcomes. However, there was an attenuation in these associations after accounting for psychosocial/behavioral factors, highlighting their roles in modifying the relationship between disease activity and pain. These findings suggest that multilevel interventions may be needed to tackle the negative effect of pain in SLE.

Emerging Characteristics of Isotonitazene-Involved Overdose Deaths: A Case-Control Study.

OBJECTIVES: Case reports of fatal overdoses involving the novel synthetic opioid isotonitazene have prompted the U.S. Drug Enforcement Administration to consider an emergency scheduling of the drug in June 2020. We aimed to epidemiologically characterize deaths involving isotonitazene. METHODS: We conducted a case control study using publicly available mortality records from January 1, 2020 to July 31, 2020 in Cook County, IL and Milwaukee County, WI. Cases (all deaths involving isotonitazene) and controls (all deaths involving other synthetic opioids) were compared on demographic characteristics, number of substances involved in fatal overdose, and co-involvement of other substances. RESULTS: We identified 40 fatal overdoses involving isotonitazene and 981 fatal overdoses involving other synthetic opioids. Isotonitazene deaths involved a significantly greater number of substances, and were significantly more likely to involve the designer benzodiazepine flualprazolam. DISCUSSION: Isotonitazene was involved in a substantial minority of synthetic opioid overdose deaths in the first 7 months of 2020. Future studies characterizing its prevalence in other markets are warranted. Emergence of highly potent novel synthetic opioids underscore the need for comprehensive health services for people with opioid use disorder.