Publications by authors named "Karen H Costenbader"

223 Publications

Assessing improved risk prediction of rheumatoid arthritis by environmental, genetic, and metabolomic factors.

Semin Arthritis Rheum 2021 Jul 10;51(5):1016-1022. Epub 2021 Jul 10.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: We sought to improve seropositive rheumatoid arthritis (RA) risk prediction using a novel weighted genetic risk score (wGRS) and preclinical plasma metabolites associated with RA risk. Predictive performance was compared to previously validated models including RA-associated environmental factors.

Methods: This nested case-control study matched incident seropositive RA cases (meeting ACR 1987 or EULAR/ACR 2010 criteria) in the Nurses' Health Studies (NHS) to two controls on age, blood collection features, and post-menopausal hormone use at pre-RA blood draw. Environmental variables were measured at the questionnaire cycle preceding blood draw. Four models were generated and internally validated using a bootstrapped optimism estimate: (a) base with environmental factors (E), (b) environmental, genetic and gene-environment interaction factors (E + G + GEI), c) environmental and metabolic factors (E + M), and d) all factors (E + G + GEI + M). A fifth model including all factors and interaction terms was fit using ridge regression and cross-validation. Models were compared using area under the receiver operating characteristic curve (AUC).

Results: 150 pre-RA cases and 455 matched controls were included. The E model yielded an optimism-corrected AUC of 0.622. The E + M model did not show improvement over the E model (corrected AUC 0.620). Including genetic factors increased prediction, producing corrected AUCs of 0.677 in the E + G + GEI model and 0.674 in the E + G + GEI + M model. Similarly, the performance of the cross-validated ridge regression model yielded an AUC of 0.657.

Conclusion: Addition of wGRS and gene-environment interaction improved seropositive RA risk prediction models. Preclinical metabolite levels did not significantly contribute to prediction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.semarthrit.2021.07.006DOI Listing
July 2021

Passive Smoking Throughout the Life Course and the Risk of Incident Rheumatoid Arthritis in Adulthood Among Women.

Arthritis Rheumatol 2021 Aug 18. Epub 2021 Aug 18.

Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.

Objective: To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking.

Methods: We analyzed the Nurses' Health Study II prospective cohort, using information collected via biennial questionnaires. We assessed the influence of (1) maternal smoking during pregnancy (in utero exposure), (2) childhood parental smoking, and (3) years lived with smokers since age 18. Incident RA and serostatus was determined by medical record review. Using the marginal structural model framework, we estimated the controlled direct effect of each passive smoking exposure on adult incident RA risk by serologic phenotype, controlling for early-life and time-updated adult factors including personal smoking.

Results: Among 90,923 women, we identified 532 incident RA cases (66% seropositive) during 27.7 years (median) of follow-up. Maternal smoking during pregnancy was associated with RA after confounding adjustment (HR 1.25 [95% CI 1.03, 1.52]), but not after accounting for subsequent smoking exposures. Childhood parental smoking was associated with seropositive RA after adjusting for confounders (HR 1.41 [95% CI 1.08, 1.83]). In the controlled direct effect analyses, childhood parental smoking was associated with seropositive RA (HR 1.75 [95% CI 1.03, 2.98]) after controlling for adult personal smoking, which was accentuated among ever smokers (HR 2.18 [95% CI 1.23, 3.88]). There was no significant association of adult passive smoking with RA (20+ years lived smoker: HR 1.30 [95% CI 0.97, 1.74] vs. none).

Conclusion: We found a potential direct influence of childhood parental smoking on adult-onset incident seropositive RA even after controlling for adult personal smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41939DOI Listing
August 2021

A Combination of Healthy Lifestyle Behaviors Reduces Risk of Incident Systemic Lupus Erythematosus.

Arthritis Rheumatol 2021 Jul 27. Epub 2021 Jul 27.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: While the association between individual factors related to lifestyle and the risk of SLE has been previously evaluated, it is unclear how the combination of these factors might affect the risk of incident SLE. We prospectively evaluated whether a combination of healthy lifestyle factors is associated with lower risk of incident SLE and its subtypes (dsDNA positive and negative).

Methods: We included 185,962 women with 203 incident SLE cases (96 anti-dsDNA positive,107 anti-dsDNA negative) during 4,649,477 person-years of follow-up from the Nurses' Health Study (NHS) and NHSII cohorts. The Healthy Lifestyle Index Score (HLIS) was calculated at baseline and approximately every 2 years in follow-up using five factors: alcohol consumption, body mass index, smoking, diet, and exercise. A time-varying Cox hazards regression model estimated the adjusted hazard ratios (HR) for SLE risk. The partial population attributable risk (PAR%) of SLE development was calculated.

Results: A higher HLIS was associated with a lower risk of SLE overall (HR 0.81 [95%CI 0.71-0.94]) and dsDNA positive SLE (HR 0.78 [95%CI 0.63-0.95]). Women with four or more healthy factors had the lowest SLE risk overall (HR 0.42 [95%CI 0.25-0.70]) and dsDNA positive SLE (HR 0.35 [95%CI 0.17-0.75]) compared to women with less than or equal to one healthy behavior. The PAR% for SLE from adhering to four or more healthy behaviors was 47.7% [95%CI 23.1-66.6].

Conclusion: Nearly half of SLE risk, a disease where significant evidence of genetic involvement has been established, might be reduced with adherence to modifiable healthy lifestyle behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41935DOI Listing
July 2021

Post-Traumatic Stress Disorder (PTSD) and Risk of Systemic Lupus Erythematosus (SLE) among Medicaid Recipients.

Arthritis Care Res (Hoboken) 2021 Jul 26. Epub 2021 Jul 26.

Division of Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital.

Objective: We studied post-traumatic stress disorder (PTSD), a severe trauma-related mental disorder, and systemic lupus erythematosus (SLE) risk in a large, diverse population enrolled in Medicaid, a U.S. government-sponsored health insurance program for low-income individuals.

Methods: We identified SLE cases and controls among patients 18-65 years old enrolled in Medicaid for ≥ 12 months in the 29 most populated US states from 2007 to 2010. SLE and PTSD case status were defined based on validated patterns of ICD-9 codes. Index date was the date of the first SLE code. Controls had no SLE codes but had another inpatient or outpatient code on the index date, and were matched 1:10 to cases by age, sex and race. Conditional logistic regressions calculated odds ratios (OR) and 95% confidence intervals (CI) for the association of PTSD with incident SLE, adjusting for smoking, obesity, oral contraceptive use, and other covariates.

Results: 10,942 incident SLE cases were matched to 109,420 controls. Prevalence of PTSD was higher in SLE cases at 10.74 cases of PTSD per 1,000 (95% CI 9.37-12.31) versus 7.83 (95% CI 7.42-8.27) in controls. The multivariable-adjusted OR for SLE among those with PTSD was 2.00 (95% CI 1.64-2.46).

Conclusion: In this large, racially and sociodemographic diverse US population, we found patients with prior PTSD diagnosis had twice the odds of a subsequent diagnosis of SLE. Studies are necessary to clarify the mechanisms driving the observed association and to inform possible interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24758DOI Listing
July 2021

Association of macronutrients and dietary patterns with risk of systemic lupus erythematosus in the Black Women's Health Study.

Am J Clin Nutr 2021 Jul 5. Epub 2021 Jul 5.

Slone Epidemiology Center at Boston University, Boston, MA, USA.

Background: Systemic lupus erythematosus (SLE) affects African-American (AA) women disproportionately. The few prospective studies assessing dietary intake in relation to risk of SLE have been conducted in predominantly white populations and have been null.

Objectives: The present study assessed associations of macronutrients and dietary patterns with risk of SLE in AA women.

Methods: Data from the Black Women's Health Study was collected prospectively via biennial questionnaires starting in 1995. Participants completed a self-administered 68-item FFQ in 1995. Self-reported SLE was verified through medical record review. We used multivariable (MV) Cox regression models to estimate HRs and 95% CIs for macronutrients, carbohydrates, proteins, total fats, PUFAs, ω-3 fatty acids, ω-6 fatty acids, MUFAs, saturated fats, trans fatty acids, Alternative Healthy Eating Index score, vegetable/fruit and meat/fried food dietary patterns, and a reduced rank regression (RRR)-derived dietary pattern in relation to SLE risk.

Results: We confirmed a total of 114 incident cases of SLE among 51,934 women during 1995-2015. MVHRs and 95% CIs for the highest quintile of intake versus the lowest were HR: 1.96, 95% CI: 1.02, 3.67 for carbohydrates; HR: 0.66, 95% CI: 0.37, 1.18 for protein; and HR: 0.54, 95% CI: 0.28, 1.01 for total fats. MUFAs, saturated fatty acids, and trans fatty acids were significantly associated with a lower risk of SLE. An RRR-derived factor, rich in fruits and sugar-sweetened drinks and low in margarines and butter, red and processed meats, fried chicken, poultry, and eggs, which explained 53.4% of the total variation of macronutrients, was the only food pattern associated with increased SLE risk (HR: 1.88, 95% CI: 1.06, 3.35).

Conclusion: These analyses suggest that a diet high in carbohydrates and low in fats is associated with increased SLE risk in AA women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab224DOI Listing
July 2021

Prescribing Patterns of Hydroxychloroquine and Corticosteroids Among Lupus Patients After New-onset End-stage Renal Disease.

Arthritis Care Res (Hoboken) 2021 Jun 13. Epub 2021 Jun 13.

Rheumatology, Inflammation and Immunity, Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, USA.

Background: Optimal strategies for managing lupus medications after end-stage renal disease (ESRD) have not been addressed. This study identifies the current United States-wide prescribing patterns of hydroxychloroquine (HCQ) and oral corticosteroids (CS), among SLE patients with incident ESRD enrolled in the US Renal Disease Systems (USRDS) registry.

Methods: We identified incident ESRD patients ≥18 years with SLE as a primary cause of ESRD between January 2006 and June 2013. Patients who were started on dialysis at ESRD onset and enrolled in Medicare Part D within 93 days as required by Medicare were included.

Results: Among the 2654 new-onset ESRD patients with Part D, the median (IQR) duration of follow-up was 761 (374, 1375) days. At baseline, 1076 (41%) were not on HCQ or CS, 220 (8%) were prescribed HCQ alone, 509 (19%) were prescribed both HCQ and CS, and 849 (32%) were prescribed CS alone. Of the 1983 patients who either never received or discontinued HCQ after ESRD onset, 667 (34%) continued CS to the end of the follow-up period. The median (IQR) CS dose was lower for patients on HCQ (14 [9, 21] mg), compared to patients who were never prescribed HCQ (15 [9, 27] mg), or patients who discontinued HCQ after ESRD (17 [10, 27] mg), p=0.001.

Conclusions: About one third of patients with lupus nephritis and new onset ESRD received CS monotherapy at high doses. As CS-related complications contribute to hospitalizations and deaths in SLE ESRD, changing these prescribing practices may improve morbidity and mortality outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24728DOI Listing
June 2021

Disparities in Lupus and Lupus Nephritis Care and Outcomes Among US Medicaid Beneficiaries.

Rheum Dis Clin North Am 2021 02 29;47(1):41-53. Epub 2020 Oct 29.

Division of Rheumatology, Inflammation and Immunity, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Office 6016P, Boston, MA 02115, USA.

Systemic lupus erythematosus (SLE) is a serious chronic autoimmune disease with substantial morbidity and mortality. Although improved diagnostics and therapeutics have contributed to declining mortality rates, important disparities exist in SLE survival rates by race, ethnicity, gender, age, country, and social disadvantage. This review highlights the burden of SLE and lupus nephritis among Medicaid beneficiaries, outlines barriers in access to high-quality SLE care and medication adherence in the Medicaid SLE population, and summarizes disparities in adverse outcomes among SLE patients enrolled in Medicaid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rdc.2020.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171807PMC
February 2021

Antibodies against human endogenous retrovirus K102 envelope activate neutrophils in systemic lupus erythematosus.

J Exp Med 2021 Jul 21;218(7). Epub 2021 May 21.

Department of Immunobiology, Yale University School of Medicine, New Haven, CT.

Neutrophil activation and the formation of neutrophil extracellular traps (NETs) are hallmarks of innate immune activation in systemic lupus erythematosus (SLE). Here we report that the expression of an endogenous retrovirus (ERV) locus ERV-K102, encoding an envelope protein, was significantly elevated in SLE patient blood and correlated with autoantibody levels and higher interferon status. Induction of ERV-K102 in SLE negatively correlated with the expression of epigenetic silencing factors. Anti-ERV-K102 IgG levels in SLE plasma correlated with higher interferon stimulated gene expression, and further promoted enhanced neutrophil phagocytosis of ERV-K102 envelope protein through immune complex formation. Finally, phagocytosis of ERV-K102 immune complexes resulted in the formation of NETs consisting of DNA, neutrophil elastase, and citrullinated histone H3. Together, we identified an immunostimulatory ERV-K envelope protein that in an immune complex with SLE IgG is capable of activating neutrophils.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1084/jem.20191766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144942PMC
July 2021

Patient experiences and strategies for coping with SLE: A qualitative study.

Lupus 2021 Aug 20;30(9):1405-1414. Epub 2021 May 20.

Division of Allergy, Immunology, and Rheumatology, Boston Children's Hospital, Boston, MA, USA.

Objective: This study explored challenges that patients with systemic lupus erythematosus (SLE) and childhood-onset SLE (cSLE) face to identify modifiable influences and coping strategies in patient experiences.

Methods: Participants were recruited from two academic medical centers through a Lupus Registry of individuals ≥18 years old and ≥4 1997 ACR classification criteria for SLE and a centralized data repository of cSLE patients, and participated in three focus groups. Transcripts were coded thematically and adjudicated by two independent reviewers.

Results: Thirteen adults, 7 (54%) with cSLE, participated in focus groups. Themes were categorized into two domains: (1) challenges with SLE diagnosis and management; and (2) patient coping strategies and modifiable factors of the SLE experience. Participants identified five primary challenges: diagnostic odyssey, public versus private face of SLE, SLE-related stresses, medication adherence, and transitioning from pediatric to adult care. Coping strategies and modifiable factors included social support, open communication about SLE, and strong patient-provider relationships. Several participants highlighted positive lessons learned through their experiences with SLE, including empathy, resilience, and self-care skills.

Conclusions: Patients with cSLE and SLE identified common challenges, modifying influences and coping strategies based on personal experiences. A strong patient-provider relationship and trust in the medical team emerged as key modifiable factors. Deriving optimism from experiences with SLE was unique to several patients diagnosed as children or young adults. Leveraging factors that improved the participants' experiences living with SLE may be used in future studies to address vulnerabilities in care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/09612033211016097DOI Listing
August 2021

Avoidable Acute Care Use for Vaccine-Preventable Illnesses Among Medicaid Beneficiaries With Lupus.

Arthritis Care Res (Hoboken) 2021 09 4;73(9):1236-1242. Epub 2021 Aug 4.

Brigham and Women's Hospital, Boston, Massachusetts.

Objective: Nearly 25% of patients with systemic lupus erythematosus (SLE) are hospitalized yearly, often for outcomes that may have been avoided if patients had received sustained outpatient care. We examined acute care use for vaccine-preventable illnesses to determine sociodemographic contributors and modifiable predictors.

Methods: Using US Medicaid claims from 29 states (2000-2010), we identified adults (18-65 years) with prevalent SLE and 12 months of enrollment prior to the first SLE code (index date) to identify baseline data. We defined acute care use for vaccine-preventable illnesses as emergency department (ED) or hospital discharge diagnoses for influenza, pneumococcal disease, meningococcal disease, herpes zoster, high-grade cervical dysplasia/cervical cancer, and hepatitis B after the index date. We estimated the incidence rate of vaccine-preventable illnesses and used Cox regression to assess risk (with hazard ratios and 95% confidence intervals) by sociodemographic factors and health care utilization, adjusting for vaccinations, comorbidities, and medications.

Results: Among 45,654 Medicaid beneficiaries with SLE, <10% had billing claims for vaccinations. There were 1,290 patients with ≥1 ED visit or hospitalization for a vaccine-preventable illness (6.6 per 1,000 person-years); 93% of events occurred in unvaccinated patients. Patients who were Black compared to White had 22% higher risk. Greater outpatient visits were associated with lower risk.

Conclusion: Medicaid beneficiaries with SLE who are not vaccinated are at risk for potentially avoidable acute care use for vaccine-preventable illnesses. Racial disparities were noted, with a higher risk among Black patients compared to White patients. Greater outpatient use was associated with reduced risk, suggesting that access to ambulatory care may reduce avoidable acute care use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24628DOI Listing
September 2021

Circulating blood metabolite trajectories and risk of rheumatoid arthritis among military personnel in the Department of Defense Biorepository.

Ann Rheum Dis 2021 Mar 22. Epub 2021 Mar 22.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis.

Methods: In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05.

Results: 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7±1.6 years; 1.0±0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (±8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking.

Conclusions: In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-219682DOI Listing
March 2021

Dairy consumption, plasma metabolites, and risk of type 2 diabetes.

Am J Clin Nutr 2021 07;114(1):163-174

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown.

Objectives: We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D.

Methods: The discovery population included 1833 participants from the Prevención con Dieta Mediterránea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses' Health Studies (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-Up Study US-based cohorts. Dairy consumption was assessed using validated FFQs. Plasma metabolites (n = 385) were profiled using LC-MS. We identified the dairy-related metabolite profiles using elastic net regularized regressions with a 10-fold cross-validation procedure. We evaluated the associations between the metabolite profiles and incident T2D in the discovery and the confirmatory cohorts.

Results: Total dairy intake was associated with 38 metabolites. C14:0 sphingomyelin (positive coefficient), C34:0 phosphatidylethanolamine (positive coefficient), and γ-butyrobetaine (negative coefficient) were associated in a directionally similar fashion with total and specific (milk, yogurt, cheese) dairy consumption. The Pearson correlation coefficients between self-reported total dairy intake and predicted total dairy intake based on the corresponding multi-metabolite profile were 0.37 (95% CI, 0.33-0.40) in the discovery cohort and 0.16 (95% CI, 0.13-0.19) in the US confirmatory cohort. After adjusting for T2D risk factors, a higher total dairy intake-related metabolite profile score was associated with a lower T2D risk [HR per 1 SD; discovery cohort: 0.76 (95% CI, 0.63-0.90); US confirmatory cohort: 0.88 (95% CI, 0.78-0.99)].

Conclusions: Total dairy intake was associated with 38 metabolites, including 3 consistently associated with dairy subtypes (C14:0 sphingomyelin, C34:0 phosphatidylethanolamine, γ-butyrobetaine). A score based on the 38 identified metabolites showed an inverse association with T2D risk in Spanish and US populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqab047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246603PMC
July 2021

The ALPHA Project: Establishing consensus and prioritisation of global community recommendations to address major challenges in lupus diagnosis, care, treatment and research.

Lupus Sci Med 2021 02;8(1)

Research, Lupus Foundation of America Inc, Washington, District of Columbia, USA.

The Addressing Lupus Pillars for Health Advancement (ALPHA) Project is a global consensus effort to identify, prioritise and address top barriers in lupus impacting diagnosis, care, treatment and research. To conduct this process, the ALPHA Project convened a multistakeholder Global Advisory Committee (GAC) of lupus experts and collected input from global audiences, including patients. In phase I, the ALPHA Project used expert interviews and a global survey of lupus experts to identify and categorise barriers into three overarching pillars: drug development, clinical care and access to care. In phase II, reported here, the GAC developed recommended actionable solutions to address these previously identified barriers through an in-person stakeholder meeting, followed by a two-round scoring process. Recommendations were assessed for feasibility, impact and timeline for implementation (FIT), where potential FIT component values were between 1 and 3 and total scores were between 3 and 9. Higher scores represented higher achievability based on the composite of the three criteria. Simplifying and standardising outcomes measures, including steroid sparing as an outcome (drug development) and defining the lupus spectrum (clinical care) ranked as the highest two priority solutions during the GAC meeting and received high FIT scores (7.67 and 7.44, respectively). Leveraging social media (access to care) received the highest FIT score across all pillars (7.86). Cross-cutting themes of many solutions include leveraging digital technology and applying specific considerations for special populations, including paediatrics. Implementing the recommendations to address key barriers to drug development, clinical care and access to care is essential to improving the quality of life of adults and children with lupus. Multistakeholder collaboration and guidance across existing efforts globally is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2020-000433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875256PMC
February 2021

American College of Rheumatology, American Academy of Dermatology, Rheumatologic Dermatology Society, and American Academy of Ophthalmology 2020 Joint Statement on Hydroxychloroquine Use With Respect to Retinal Toxicity.

Arthritis Rheumatol 2021 06 26;73(6):908-911. Epub 2021 Apr 26.

Stanford University Medical Center, Stanford, California.

Four major medical societies involved with hydroxychloroquine (HCQ) therapy concur on the need for common principles and cooperation to minimize the risk of ocular toxicity. At a daily dosage of ≤5 mg/kg/day actual body weight, the risk of retinal toxicity from HCQ is <2% for usage up to 10 years. Widespread adoption of more sensitive testing techniques, such as optical coherence tomography and automated visual fields, by eye care providers will allow the detection of early toxicity and thus preserve the patient's visual function. Baseline testing is advised to rule out confounding disease when a patient is started on HCQ. Annual screening with sensitive tests should begin no more than 5 years after treatment initiation. Providers should be sensitive to the medical value of HCQ, and not stop the drug for uncertain indications. It is important to note that effective communication among prescribing physicians, patients, and eye care providers will optimize the utility and safety of HCQ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41683DOI Listing
June 2021

Predictors of Initial Hydroxychloroquine Receipt among Medicaid Beneficiaries with Incident Systemic Lupus Erythematosus.

Arthritis Care Res (Hoboken) 2021 Feb 8. Epub 2021 Feb 8.

Division of Rheumatology, Inflammation and Immunity, BWH/Harvard Medical School, United States.

Objective: Although hydroxychloroquine/chloroquine (HCQ/CQ) form the cornerstone of systemic lupus erythematosus (SLE) treatment, not all patients receive this, which may contribute to disparities in outcomes. We investigated factors associated with first dispensing of HCQ/CQ.

Methods: Using Medicaid insurance claims from 2000-2010, we identified individuals age 18-65 years with incident SLE (≥3 SLE ICD-9 codes separated by ≥30 days without prior SLE codes or HCQ/CQ use for 24 months.) The primary outcome was first dispensing of HCQ/CQ within 24 months of the first SLE code. We used Cox proportional hazards regression models to examine the association between sociodemographic factors, comorbidities, health care utilization and medication use and HCQ/CQ dispensing within 24 months of diagnosis.

Results: We identified 9560 Medicaid beneficiaries with incident SLE; 41% received HCQ (N=3949) or CQ (N=14) within 24 months of diagnosis. Younger patients were more likely to receive HCQ/CQ. Black, Asian, Hispanic and American Indian/Alaska Native individuals were more likely to receive HCQ/CQ than White individuals. Alcohol, opioid, and nicotine use, diabetes, and end-stage renal disease were associated with lower dispensing. Outpatient appointments and preventive care services were associated with higher rates; more hospitalizations with lower rates.

Conclusion: Only 41% of Medicaid beneficiaries with SLE received HCQ/CQ within 24 months of diagnosis. Greater outpatient and preventive care increased receipt. All non-White race/ethnicities had higher rates of first dispensing. Time to initial HCQ/CQ dispensing may not explain racial/ethnic disparities in adverse outcomes, highlighting the need to consider other care quality-related issues and medication adherence challenges.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349369PMC
February 2021

Reply.

Arthritis Rheumatol 2021 05 11;73(5):901-902. Epub 2021 Mar 11.

Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41642DOI Listing
May 2021

Comparative risks of cardiovascular disease events among SLE patients receiving immunosuppressive medications.

Rheumatology (Oxford) 2021 08;60(8):3789-3798

Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Objectives: SLE patients have elevated cardiovascular disease (CVD) risk, but it is unclear whether this risk is affected by choice of immunosuppressive drug. We compared CVD risks among SLE patients starting MMF, CYC or AZA.

Methods: Using Medicaid Analytic eXtract (2000-2012), adult SLE patients starting MMF, CYC or AZA were identified and propensity scores (PS) were estimated for receipt of MMF vs CYC and MMF vs AZA. We examined rates of first CVD event (primary outcome), all-cause mortality, and a composite of first CVD event and all-cause mortality (secondary outcomes). After 1:1 PS-matching, Fine-Gray regression models estimated subdistribution hazard ratios (HRs.d.) for risk of CVD events. Cox regression models estimated HRs for all-cause mortality. The primary analysis was as-treated; 6- and 12-month intention-to-treat (ITT) analyses were secondary.

Results: We studied 680 PS-matched pairs of patients with SLE initiating MMF vs CYC and 1871 pairs initiating MMF vs AZA. Risk of first CVD event was non-significantly reduced for MMF vs CYC [HRs.d 0.72 (95% CI: 0.37, 1.39)] and for MMF vs AZA [HRs.d 0.88 (95% CI: 0.59, 1.32)] groups. In the 12-month ITT, first CVD event risk was lower among MMF than AZA new users [HRs.d 0.68 (95% CI: 0.47, 0.98)].

Conclusion: In this head-to-head PS-matched analysis, CVD event risks among SLE patients starting MMF vs CYC or AZA were not statistically reduced except in one 12-month ITT analysis of MMF vs AZA, suggesting longer-term use may convey benefit. Further studies of potential cardioprotective benefit of MMF are necessary.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328499PMC
August 2021

Corticosteroid dosing and opioid use are high in patients with SLE and remain elevated after belimumab initiation: a retrospective claims database analysis.

Lupus Sci Med 2020 12;7(1)

Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: To investigate corticosteroid and opioid use among patients with SLE and to examine the impact of belimumab initiation on the use of other SLE therapies.

Methods: We identified adult patients with SLE (International Classification of Diseases, 9th Revision/10th Revision 710.0 and M32) between 1 January 2012 and 31 May 2018 (earliest SLE diagnosis=index date) within MarketScan administrative claims data. Patients were followed from index date for a minimum of 12 months and until the earlier of disenrolment in their health plan or study end (31 May 2018). Corticosteroid utilisation, corticosteroid dose (in prednisone equivalents) and opioid utilisation (overall, by strength (weak, strong) and by duration (chronic use defined as >90 days of cumulative drug supply)) were measured during follow-up. Oral corticosteroid and opioid use were compared in the 6 months before and after initiation of belimumab.

Results: There were 49 413 patients with SLE eligible for analysis (mean (SD) age: 50.1 (14.0) years, 90.2% female). Of these, 68.5% received corticosteroids, and the average number of prescriptions was 4.59 (4.11) over the first 12 months of follow-up. Among patients with oral corticosteroids, average daily dose was 19.4 (14.2) mg and 59.6% had an average daily dose of ≥15 mg. Half (52.6%) had at least one opioid prescription and of these, 34.6% had chronic use over the first 12 months of follow-up. Among patients initiating belimumab during follow-up (n=1710), oral corticosteroid use decreased by 9.1% (p=0.001), and average daily dose decreased from 14.5 (18.4) mg to 11.9 (18.0) mg (p<0.001) in the 6 months after initiation compared with the 6 months prior. Initiation of belimumab had no impact on prevalence of opioid use.

Conclusions: A high proportion of patients with SLE are treated with corticosteroids to control SLE and opioid therapy to manage chronic pain. While there was no change in opioid use, oral corticosteroid use and dose intensity decreased following initiation of belimumab.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2020-000435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759957PMC
December 2020

Systemic lupus erythematosus symptom clusters and their association with patient-reported outcomes and treatment: Analysis of real-world data.

Arthritis Care Res (Hoboken) 2020 Dec 20. Epub 2020 Dec 20.

Brigham and Women's Hospital, Boston, MA, USA.

Objective: To identify discrete clusters of systemic lupus erythematosus (SLE) patients based on symptoms and investigate differences across clusters.

Methods: Data were collected in the United States of America and five European countries via the Adelphi Real World Lupus Disease Specific Programme™, a cross-sectional survey. Rheumatologists provided data for five consecutively consulting adult patients with SLE, who were invited to participate. Identified SLE symptoms were reduced to factors based on commonly concurrent symptoms, using principal-component factor analysis. Factors were used as covariates in a latent class cluster analysis to identify discrete patient clusters. Patient-reported outcomes and physician-reported data were compared across clusters.

Results: Among 1,376 patients, 87% of patients were female and 74% of patients were white. We identified four patient clusters ("very mild", "mild", "moderate", "severe") based on 39 signs/symptoms. Physician-reported symptom burden, organ involvement, disease activity and number of flares increased with increasing cluster severity (p<0.0001). Patient-reported impact (health status, fatigue, work productivity impairment, anxiety/depression, emotional impact) increased with increasing cluster severity (p<0.0001). Glucocorticoid and immunosuppressant use increased, and anti-malarial use decreased, with increasing cluster severity. In all clusters, <20% of patients received biologics; >15% of patients not receiving biologics were considered eligible for treatment by their physician. The proportion of physicians and patients satisfied with treatment decreased with increasing cluster severity (p<0.0001).

Conclusion: Our large, international real-world survey of SLE patients and physicians demonstrated strong associations between increased impairment, organ involvement and humanistic burden in SLE, highlighting unmet need for effective treatment options in high disease activity patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24546DOI Listing
December 2020

A prospective study of reproductive factors in relation to risk of systemic lupus erythematosus among black women.

Lupus 2021 Feb 24;30(2):204-210. Epub 2020 Nov 24.

Slone Epidemiology Center, Boston University, Boston, MA, USA.

Objective: Systemic lupus erythematosus (SLE) occurs most commonly among reproductive age women, compatible with a potential role of reproductive factors, although past studies including women of mainly European ancestry have yielded conflicting results. We assessed relationships of reproductive factors to SLE risk among black women.

Methods: We followed 58,243 participants in the Black Women's Health Study (BWHS) from 1995 - 2015 using biennial health questionnaires, on which participants reported reproductive and other factors. Self-reported incident SLE cases were confirmed as meeting 1997 American College of Rheumatology SLE classification criteria by medical record review. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for SLE for several reproductive factors, controlling for potential confounders.

Results: During 954,476 person-years of follow-up, 125 incident cases of SLE were confirmed. Later age at menarche and longer duration of breast feeding were associated with increased risk of SLE. The multivariable HRs were 2.31 (95% CI, 1.30-4.11) for age at menarche ≥15 relative to age 12, and 1.73 (95% CI, 1.01-2.94) for breast feeding ≥6 months relative to none. There were no clear associations with parity, age at first birth, menopausal status, hysterectomy, age at menopause, or history of endometriosis.

Conclusion: Our results suggest that later menarchal age and breastfeeding of infants for ≥6 months vs. none may be associated with increased SLE risk among black women, while other reproductive factors did not appear related. The biological mechanisms underlying these potential associations should be pursued.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0961203320973074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854483PMC
February 2021

One-Year Effects of Omega-3 Treatment on Fatty Acids, Oxylipins, and Related Bioactive Lipids and Their Associations with Clinical Lipid and Inflammatory Biomarkers: Findings from a Substudy of the Vitamin D and Omega-3 Trial (VITAL).

Metabolites 2020 Oct 27;10(11). Epub 2020 Oct 27.

Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women's Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) < 0.05 in VITAL200, validated (-values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids. N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/metabo10110431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693376PMC
October 2020

Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies.

Arthritis Care Res (Hoboken) 2020 Oct 7. Epub 2020 Oct 7.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Non-white people are more likely to develop systemic lupus erythematosus (SLE), yet are underrepresented in SLE clinical trials. The efficacy and safety of drugs may be influenced by ancestry, and ancestrally diverse study populations are necessary to optimize treatments across the full spectrum of patients. However, barriers to entry into clinical trials are amplified in non-white populations. To address these issues, a conference was held in Bethesda, Maryland from October 15 -16 , 2019 entitled "Increasing Ancestral Diversity in Systemic Lupus Erythematosus Clinical Studies: Overcoming the Barriers." Participants included people with lupus, lupus physicians, lupus clinical trialists, treatment developers from biotechnology, social scientists, patient advocacy groups, and United States government representatives (the Office of Minority Health, Centers for Disease Control and Prevention, National Institutes of Health, and the Food and Drug Administration). For all of these groups, the organizers purposefully included people of non-white ancestry. Decreased participation of non-white SLE patients in clinical research was evaluated through historical, societal, experiential, and pragmatic perspectives, and several interventional programs to increase non-white patient participation in SLE and non-SLE research were described and discussed. The presentations and discussions highlighted the need for changes at the societal, institutional, research team, referring physician, and patient education levels to achieve equitable ancestral representation in SLE clinical studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24474DOI Listing
October 2020

Interactions Between Genome-Wide Genetic Factors and Smoking Influencing Risk of Systemic Lupus Erythematosus.

Arthritis Rheumatol 2020 11 23;72(11):1863-1871. Epub 2020 Sep 23.

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: To identify interactions between genetic factors and current or recent smoking in relation to risk of developing systemic lupus erythematosus (SLE).

Methods: For the study, 673 patients with SLE (diagnosed according to the American College of Rheumatology 1997 updated classification criteria) were matched by age, sex, and race (first 3 genetic principal components) to 3,272 control subjects without a history of connective tissue disease. Smoking status was classified as current smoking/having recently quit smoking within 4 years before diagnosis (or matched index date for controls) versus distant past/never smoking. In total, 86 single-nucleotide polymorphisms and 10 classic HLA alleles previously associated with SLE were included in a weighted genetic risk score (wGRS), with scores dichotomized as either low or high based on the median value in control subjects (low wGRS being defined as less than or equal to the control median; high wGRS being defined as greater than the control median). Conditional logistic regression models were used to estimate both the risk of SLE and risk of anti-double-stranded DNA autoantibody-positive (dsDNA+) SLE. Additive interactions were assessed using the attributable proportion (AP) due to interaction, and multiplicative interactions were assessed using a chi-square test (with 1 degree of freedom) for the wGRS and for individual risk alleles. Separate repeated analyses were carried out among subjects of European ancestry only.

Results: The mean ± SD age of the SLE patients at the time of diagnosis was 36.4 ± 15.3 years. Among the 673 SLE patients included, 92.3% were female and 59.3% were dsDNA+. Ethnic distributions were as follows: 75.6% of European ancestry, 4.5% of Asian ancestry, 11.7% of African ancestry, and 8.2% classified as other ancestry. A high wGRS (odds ratio [OR] 2.0, P = 1.0 × 10 versus low wGRS) and a status of current/recent smoking (OR 1.5, P = 0.0003 versus distant past/never smoking) were strongly associated with SLE risk, with significant additive interaction (AP 0.33, P = 0.0012), and associations with the risk of anti-dsDNA+ SLE were even stronger. No significant multiplicative interactions with the total wGRS (P = 0.58) or with the HLA-only wGRS (P = 0.06) were found. Findings were similar in analyses restricted to only subjects of European ancestry.

Conclusion: The strong additive interaction between an updated SLE genetic risk score and current/recent smoking suggests that smoking may influence specific genes in the pathogenesis of SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722161PMC
November 2020

Depression and Subsequent Risk for Incident Rheumatoid Arthritis Among Women.

Arthritis Care Res (Hoboken) 2021 01;73(1):78-89

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: To investigate the association of depression with subsequent risk of rheumatoid arthritis (RA) by serologic phenotype.

Methods: We performed a cohort study using pooled data from the Nurses' Health Study (NHS; 1992-2014) and the NHSII (1993-2015). Depression was defined according to the following composite definition: diagnosis by clinician, regular antidepressant use, or a 5-question Mental Health Inventory score of <60 using time-updated questionnaires during follow-up. Incident RA cases met research criteria by medical record review. Information on covariates, including smoking, diet, and body mass index, was obtained using questionnaires. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RA risk (overall and by serologic phenotype) according to depression status and adjusted for potential confounders. All analyses included a time separation between assessments of depression and the window for RA risk of at least 4 years to lower the possibility that depressive symptoms due to early RA prior to diagnosis explained any associations.

Results: Among 195,358 women, we identified 858 cases of incident RA (65% seropositive) over 3,087,556 person-years (median 17.9 years per participant). Compared to women without depression, those with depression had multivariable HRs as follows: 1.28 (95% CI 1.10-1.48) for all RA; 1.12 (95% CI 0.93-1.35) for seropositive RA; and 1.63 (95% CI 1.27-2.09) for seronegative RA. When analyzing components of the composite depression exposure variable, regular antidepressant use was not associated with subsequent seropositive RA (HR 1.21 [95% CI 0.97-1.49]) and was associated with seronegative RA (HR 1.75 [95% CI 1.32-2.32]).

Conclusion: Indicators of depression, specifically antidepressant use, were associated with subsequent increased risk for seronegative RA, and this finding was not explained by measured lifestyle factors prior to clinical presentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775283PMC
January 2021

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses' Health Study and Nurses' Health Study II.

Arthritis Care Res (Hoboken) 2021 09 6;73(9):1250-1258. Epub 2021 Aug 6.

Brigham and Women's Hospital, Boston, Massachusetts.

Objective: Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti-double-stranded DNA (anti-dsDNA) positive versus negative subtypes.

Methods: We studied 79,568 women in the Nurses' Health Study (1984-2014) and 93,554 in the Nurses' Health Study II (1991-2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI-2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time-varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti-dsDNA, for cumulative average dietary quality score tertiles and individual AHEI-2010 components.

Results: We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI-2010 HR 0.78 [95% CI 0.54-1.14], aMed HR 0.82 [95% CI 0.56-1.18], DASH HR 1.16 [95% CI 0.81-1.66], EDIP HR 0.83 [95% CI 0.57-1.21]). No association was demonstrated for anti-dsDNA+ or anti-dsDNA- SLE risk. Women in the highest (versus lowest) AHEI-2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40-0.87]). No association was demonstrated for other AHEI-2010 components and SLE risk.

Conclusion: We observed no association between long-term adherence to the AHEI-2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960564PMC
September 2021

A lipid-related metabolomic pattern of diet quality.

Am J Clin Nutr 2020 12;112(6):1613-1630

Channing Division of Network Medicine Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.

Background: Adherence to a healthy diet has been associated with reduced risk of chronic diseases. Identifying nutritional biomarkers of diet quality may be complementary to traditional questionnaire-based methods and may provide insights concerning disease mechanisms and prevention.

Objective: To identify metabolites associated with diet quality assessed via the Alternate Healthy Eating Index (AHEI) and its components.

Methods: This cross-sectional study used FFQ data and plasma metabolomic profiles, mostly lipid related, from the Nurses' Health Study (NHS, n = 1460) and Health Professionals Follow-up Study (HPFS, n = 1051). Linear regression models assessed associations of the AHEI and its components with individual metabolites. Canonical correspondence analyses (CCAs) investigated overlapping patterns between AHEI components and metabolites. Principal component analysis (PCA) and explanatory factor analysis were used to consolidate correlated metabolites into uncorrelated factors. We used stepwise multivariable regression to create a metabolomic score that is an indicator of diet quality.

Results: The AHEI was associated with 83 metabolites in the NHS and 96 metabolites in the HPFS after false discovery rate adjustment. Sixty-three of these significant metabolites overlapped between the 2 cohorts. CCA identified "healthy" AHEI components (e.g., nuts, whole grains) and metabolites (n = 27 in the NHS and 33 in the HPFS) and "unhealthy" AHEI components (e.g., red meat, trans fat) and metabolites (n = 56 in the NHS and 63 in the HPFS). PCA-derived factors composed of highly saturated triglycerides, plasmalogens, and acylcarnitines were associated with unhealthy AHEI components while factors composed of highly unsaturated triglycerides were linked to healthy AHEI components. The stepwise regression analysis contributed to a metabolomics score as a predictor of diet quality.

Conclusion: We identified metabolites associated with healthy and unhealthy eating behaviors. The observed associations were largely similar between men and women, suggesting that metabolomics can be a complementary approach to self-reported diet in studies of diet and chronic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ajcn/nqaa242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727474PMC
December 2020

Impact of reported NSAID "allergies" on opioid use disorder in back pain.

J Allergy Clin Immunol 2021 04 9;147(4):1413-1419. Epub 2020 Sep 9.

Division of Allergy and Clinical Immunology, Department of Medicine, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.

Background: It is crucial to identify patients at highest risk for opioid use disorder (OUD) and to address challenges in reducing opioid use. Reported nonsteroidal anti-inflammatory drug (NSAID) allergies may predispose to use of stronger pain medications and potentially to OUD.

Objective: We sought to investigate the clinical impact of reported NSAID allergy on OUD in patients with chronic back pain.

Methods: We conducted a retrospective study of adults receiving care at a tertiary health care system from January 1, 2013, to December 31, 2018. Back pain and OUD were identified using administrative data algorithms. We used propensity score matching and logistic regression to estimate the impact of self-reported NSAID adverse drug reactions (ADRs) on risk of OUD, adjusting for other relevant clinical information.

Results: Of 47,114 patients with chronic back pain, 3,620 (7.7%) had a reported NSAID ADR. In an adjusted propensity score-matched analysis, patients with NSAID ADRs had higher odds (odds ratio, 1.34; 95% CI, 1.07-1.67) of developing OUD as compared with those without NSAID ADRs. Additional risk factors for OUD included younger age, male sex, Medicaid insurance, Medicare insurance, higher number of inpatient and outpatient visits in the previous year, and comorbid anxiety and depression. Patients with listed NSAID ADRs also had higher odds of a documented opioid prescription during the study period (odds ratio, 1.22; 95% CI, 1.11-1.34).

Conclusions: Adults with chronic back pain and reported NSAID ADRs are at a higher risk of developing OUD and receiving opioid analgesics, even after accounting for comorbidities and health care utilization. Allergy evaluation is critical for potential delabeling of patients with reported NSAID allergies and chronic pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaci.2020.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995999PMC
April 2021

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

Ann Rheum Dis 2020 10 14;79(10):1333-1339. Epub 2020 Aug 14.

Rheumatology, Azienda Ospedaliero Universitaria Pisana, Pisa, Toscana, Italy.

Objectives: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria.

Methods: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated.

Results: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%).

Conclusions: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-217162DOI Listing
October 2020

Gastrointestinal SLE involvement in SLE classification. Response to: ''2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus' by Aringer ' by Cui .

Ann Rheum Dis 2020 Aug 4. Epub 2020 Aug 4.

Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University Health Network, Mount Sinai Hospital, University of Toronto, Toronto Scleroderma Research Program, Toronto, Ontario, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-218615DOI Listing
August 2020
-->