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Background: ANCA-associated vasculitis (AAV) is a rare but serious disease. Traditional case-identification methods using claims data can be time-intensive and may miss important subgroups. We hypothesized that a deep learning model analyzing electronic health records (EHR) can more accurately identify AAV cases. Methods: We examined the Mass General Brigham (MGB) repository of clinical documentation from 12/1/1979 to 5/11/2021, using expert-curated keywords and ICD codes to identify a large cohort of potential AAV cases. Three labeled datasets (I, II, III) were created, each containing note sections. We trained and evaluated a range of machine learning and deep learning algorithms for note-level classification, using metrics like positive predictive value (PPV), sensitivity, F-score, area under the receiver operating characteristic curve (AUROC), and area under the precision and recall curve (AUPRC). The deep learning model was further evaluated for its ability to classify AAV cases at the patient-level, compared with rule-based algorithms in 2,000 randomly chosen samples. Results: Datasets I, II, and III comprised 6,000, 3,008, and 7,500 note sections, respectively. Deep learning achieved the highest AUROC in all three datasets, with scores of 0.983, 0.991, and 0.991. The deep learning approach also had among the highest PPVs across the three datasets (0.941, 0.954, and 0.800, respectively). In a test cohort of 2,000 cases, the deep learning model achieved a PPV of 0.262 and an estimated sensitivity of 0.975. Compared to the best rule-based algorithm, the deep learning model identified six additional AAV cases, representing 13% of the total. Conclusion: The deep learning model effectively classifies clinical note sections for AAV diagnosis. Its application to EHR notes can potentially uncover additional cases missed by traditional rule-based methods.
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STUDY QUESTION: What is the association between reproductive health history (e.g. age at menarche, menopause, reproductive lifespan) with abdominal adiposity in postmenopausal women? SUMMARY ANSWER: Higher visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) tissue levels were observed among women with earlier menarche, earlier menopause, and greater parity. WHAT IS KNOWN ALREADY: Postmenopausal women are predisposed to accumulation of VAT and SAT. Reproductive health variables are known predictors of overall obesity status in women, defined by BMI. STUDY DESIGN, SIZE, DURATION: This study is a secondary analysis of data collected from the baseline visit of the Women's Health Initiative (WHI). The WHI is a large prospective study of postmenopausal women, including both a randomized trial and observational study. There were 10 184 women included in this analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data were collected from a reproductive health history questionnaire, dual-energy x-ray absorptiometry scans, and anthropometric measures at WHI baseline. Reproductive history was measured via self-report, and included age at menarche, variables related to pregnancy, and age at menopause. Reproductive lifespan was calculated as age at menopause minus age at menarche. Statistical analyses included descriptive analyses and multivariable linear regression models to examine the association between reproductive history with VAT, SAT, total body fat, and BMI. MAIN RESULTS AND THE ROLE OF CHANCE: Women who reported early menarche (<10 years) or early menopause (<40 years) had the highest levels of VAT. Adjusted multivariable linear regression results demonstrate women who experienced menarche >15 years had 23 cm2 less VAT (95% CI: -31.4, -14.4) and 47 cm2 less SAT (95% CI: -61.8, -33.4) than women who experienced menarche at age 10 years or earlier. A similar pattern was observed for age at menopause: compared to women who experienced menopause <40 years, menopause at 50-55 years was associated with 19.3 cm2 (95% CI: -25.4, -13.3) less VAT and 27.4 cm2 (-29.6, 10.3) less SAT. High parity (>3 pregnancies) was also associated with VAT and SAT. For example, adjusted beta coefficients for VAT were 8.36 (4.33, 12.4) and 17.9 (12.6, 23.2) comparing three to four pregnancies with the referent, one to two pregnancies. LIMITATIONS, REASONS FOR CAUTION: The WHI reproductive health history questionnaire may be subject to poor recall owing to a long look-back window. Residual confounding may be present given lack of data on early life characteristics, such as maternal and pre-menarche characteristics. WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to our understanding of reproductive lifespan, including menarche and menopause, as an important predictor of late-life adiposity in women. Reproductive health has also been recognized as a sentinel marker for chronic disease in late life. Given established links between adiposity and cardiometabolic outcomes, this research has implications for future research, clinical practice, and public health policy that makes use of reproductive health history as an opportunity for chronic disease prevention. STUDY FUNDING/COMPETING INTEREST(S): HRB and AOO are supported by the National Institute of Health National Institute of Aging (R01AG055018-04). JWB reports royalties from 'ACSM'S Body Composition Assessment Book' and consulting fees from the WHI. The remaining authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.
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Menarca , Pós-Menopausa , História Reprodutiva , Humanos , Feminino , Pós-Menopausa/fisiologia , Pessoa de Meia-Idade , Menarca/fisiologia , Idoso , Estudos Prospectivos , Saúde da Mulher , Gordura Abdominal , Gravidez , Índice de Massa Corporal , Paridade/fisiologia , Menopausa/fisiologia , Gordura Intra-Abdominal , Adiposidade/fisiologiaRESUMO
The recent push toward understanding an individual cell's behavior and identifying cellular heterogeneity has created an unmet need for technologies that can probe live cells at the single-cell level. Cells within a population are known to exhibit heterogeneous responses to environmental cues. These differences can lead to varied cellular states, behavior, and responses to therapeutics. Techniques are needed that are not only capable of processing and analyzing cellular populations at the single cell level, but also have the ability to isolate specific cell populations from a complex sample at high throughputs. The new CellMag-Coalesce-Attract-Resegment Wash (CellMag-CARWash) system combines positive magnetic selection with droplet microfluidic devices to isolate cells of interest from a mixture with >93% purity and incorporate treatments within individual droplets to observe single cell biological responses. This workflow is shown to be capable of probing the single cell extracellular vesicle (EV) secretion of MCF7 GFP cells. This article reports the first measurement of ß-Estradiol's effect on EV secretion from MCF7 cells at the single cell level. Single cell processing revealed that MCF7 GFP cells possess a heterogeneous response to ß-Estradiol stimulation with a 1.8-fold increase relative to the control.
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Separação Celular , Análise de Célula Única , Humanos , Análise de Célula Única/métodos , Análise de Célula Única/instrumentação , Células MCF-7 , Separação Celular/métodos , Separação Celular/instrumentação , Dispositivos Lab-On-A-Chip , Vesículas Extracelulares/fisiologia , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Ensaios de Triagem em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/métodos , Estradiol/farmacologiaRESUMO
OBJECTIVES: IgG4-related disease (IgG4-RD) can affect nearly any organ and is often treated with glucocorticoids, which contribute to organ damage and toxicity. Comorbidities and healthcare utilization in IgG4-RD are poorly understood. METHODS: We conducted a cohort study using claims data from a United States managed care organization. Incident IgG4-RD cases were identified using a validated algorithm; general population comparators were matched by age, sex, race/ethnicity, and index date. The frequency of 21 expert-defined clinical outcomes associated with IgG4-RD or its treatment and healthcare-associated visits and costs were assessed 12 months before and 36 months after the index date (date of earliest IgG4-RD-related claim). RESULTS: There were 524 cases and 5,240 comparators. Most cases received glucocorticoids prior to (64.0%) and after (85.1%) the index date. Nearly all outcomes, many being common glucocorticoid toxicities, occurred more frequently in cases vs comparators. During follow-up, the largest differences between cases and comparators were seen for gastroesophageal reflux disease (prevalence difference: +31.2%, p< 0.001); infections (+17.3%, p< 0.001); hypertension (+15.5%, p< 0.01); and diabetes mellitus (+15.0%, p< 0.001). The difference in malignancy increased during follow-up from +8.8% to + 12.5% (p< 0.001). 17.4% of cases used pancreatic enzyme replacement therapy during follow-up. Over follow-up, cases were more often hospitalized (57.3% vs 17.2%, p< 0.01) and/or had an ER visit (72.0% vs 36.7%, p< 0.01); all costs were greater in cases than comparators. CONCLUSIONS: Patients with IgG4-RD are disproportionately affected by adverse outcomes, some of which may be preventable or modifiable with vigilant clinician monitoring. Glucocorticoid-sparing treatments may improve these outcomes.
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OBJECTIVE: Many individuals with rheumatic disease are at higher risk for severe acute coronavirus disease 2019 (COVID-19). We aimed to evaluate risk factors for postacute sequelae of COVID-19 (PASC) using an electronic health record (EHR)-based definition. METHODS: We identified patients with prevalent rheumatic diseases and COVID-19 within the Mass General Brigham healthcare system. PASC was defined by the International Classification of Diseases, 10th revision (ICD-10) codes, relevant labs, vital signs, and medications at least 30 days following the first COVID-19 infection. Patients were followed until the earliest of incident PASC, repeat COVID-19 infection, 1 year of follow-up, death, or February 19, 2023. We used multivariable Cox regression to estimate the association of baseline characteristics with PASC risk. RESULTS: Among 2459 patients (76.37% female, mean age 57.4 years), the most common incident PASC manifestations were cough (14.56%), dyspnea (12.36%), constipation (11.39%), and fatigue (10.70%). Serious manifestations including acute coronary disease (4.43%), thromboembolism (3.09%), hypoxemia (3.09%), stroke (1.75%), and myocarditis (0.12%) were rare. The Delta wave (adjusted hazard ratio [aHR] 0.63, 95% CI 0.49-0.82) and Omicron era (aHR 0.50, 95% CI 0.41-0.62) were associated with lower risk of PASC than the early pandemic period (March 2020-June 2021). Age, obesity, comorbidity burden, race, and hospitalization for acute COVID-19 infection were associated with greater risk of PASC. Glucocorticoid (GC) use (aHR 1.19, 95% CI 1.05-1.34 compared to no use) was associated with greater risk of PASC. CONCLUSION: Among patients with rheumatic diseases, following their first COVID-19 infection, we found a decreased risk of PASC over calendar time using an EHR-based definition. Aside from GCs, no specific immunomodulatory medications were associated with increased risk, and risk factors were otherwise similar to those seen in the general population.
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COVID-19 , Registros Eletrônicos de Saúde , Doenças Reumáticas , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/complicações , Idoso , Fatores de Risco , SARS-CoV-2 , Adulto , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/complicações , Síndrome de COVID-19 Pós-Aguda , ComorbidadeRESUMO
BACKGROUND: Patients with systemic autoimmune rheumatic diseases using disease-modifying antirheumatic drugs (DMARDs) might have blunted responses to COVID-19 vaccines. The initial mRNA vaccine series is defined as three doses for this population and a fourth booster dose is recommended. The effectiveness of the fourth dose in patients with systemic autoimmune rheumatic diseases using DMARDs is not well established. We aimed to assess the effectiveness of receiving versus not receiving a fourth dose of COVID-19 mRNA vaccine using a target trial framework, in a cohort of patients with systemic autoimmune rheumatic diseases receiving DMARD therapy. METHODS: We conducted an emulated target trial using observational data from the Mass General Brigham health-care system to compare receiving versus not receiving a fourth mRNA vaccine dose. Analysed patients had systemic autoimmune rheumatic diseases, were prescribed DMARDs, and were eligible for a fourth dose of BNT162b2 or mRNA-1273 vaccines between Jan 16 and June 11, 2022. To account for temporal changes, the study period was divided into 1-week intervals. Fourth-dose-exposed patients were included in a 1-week interval if they received a fourth mRNA dose in that interval; fourth-dose-unexposed patients were eligible for but had not received the fourth dose of the vaccine. The primary outcome was a SARS-CoV-2 infection; the secondary outcome was severe SARS-CoV-2 infection (ie, admission to hospital or death within -3 to +14 days of a positive test). We assessed the effectiveness of the fourth dose using time-stratified, overlap propensity score-weighted Cox regression models. FINDINGS: We included 4305 patients, 3126 of whom received a fourth dose of vaccine and 1179 who had not. The median follow-up time was 135 days (IQR 112-154) among patients who had received a fourth dose and 65 days (30-156) among patients who had not received a fourth dose. After overlap weighting in both groups, 1863 (72·7%) of 2563 participants were women, 700 (27·3%) were men, and 2242 (87·5%) were White. Rheumatoid arthritis was present in 1392 (54·3%) of 2563 participants; the most frequent treatments were conventional synthetic DMARDs (1489 [58·1%]) or biological DMARDs (1007 [39·3%]). SARS-CoV-2 infection risk was lower among patients receiving versus not receiving a fourth dose of vaccine (HR 0·59 [95% CI 0·47-0·74]). A fourth dose reduced the risk of admission to hospital or death within -3 to +14 days of SARS-CoV-2 infection (0·35 [0·14-0·85]). INTERPRETATION: In this emulated target trial, a fourth dose of COVID-19 mRNA vaccine reduced the risk of SARS-CoV-2 infection and severe COVID-19 among patients with systemic autoimmune rheumatic diseases using DMARDs during the Omicron era. Patients with systemic autoimmune rheumatic diseases should be encouraged to remain up-to-date with COVID-19 vaccinations. FUNDING: The National Institutes of Health and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
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Antirreumáticos , Artrite Reumatoide , COVID-19 , Feminino , Humanos , Masculino , Antirreumáticos/uso terapêutico , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Vacinas de mRNA , RNA Mensageiro , SARS-CoV-2 , Estados UnidosRESUMO
OBJECTIVE: To determine the incidence and baseline factors associated with breakthrough coronavirus disease 2019 (COVID-19) after preexposure prophylaxis (PrEP) with tixagevimab/cilgavimab among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: We performed a retrospective cohort study among patients with SARDs who received tixagevimab/cilgavimab between January 2, 2022, and November 16, 2022. The primary outcome was breakthrough COVID-19 after tixagevimab/cilgavimab. We performed multivariable Cox regression models adjusted for baseline factors to identify risk factors for breakthrough COVID-19. RESULTS: We identified 444 patients with SARDs who received tixagevimab/cilgavimab (mean age 62.0 years, 78.2% female). There were 83 (18.7%) breakthrough COVID-19 cases (incidence rate 31.5/1000 person-months, 95% CI 24.70-38.24), 7 (1.6%) hospitalizations, and 1 (0.2%) death. Older age was inversely associated with breakthrough COVID-19 (adjusted hazard ratio [aHR] 0.86/10 years, 95% CI 0.75-0.99). Higher baseline spike antibody levels were associated with lower risk of breakthrough COVID-19 (aHR 0.42, 95% CI 0.18-0.99 for spike antibody levels > 200 vs < 0.4 units). CD20 inhibitor users had a similar risk of breakthrough COVID-19 (aHR 1.05, 95% CI 0.44-2.49) compared to conventional synthetic disease-modifying antirheumatic drug (DMARD) users. CONCLUSION: We found that patients with SARDs had frequent breakthrough COVID-19, but the proportion experiencing severe COVID-19 was low. DMARD type, including CD20 inhibitors, did not significantly affect risk of breakthrough COVID-19. Evidence of prior humoral immunity was protective against breakthrough infection, highlighting the continued need for a multimodal approach to prevent severe COVID-19 as novel PrEP therapies are being developed.
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Anticorpos Monoclonais , Antirreumáticos , COVID-19 , Doenças Reumáticas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Antirreumáticos/uso terapêutico , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológicoRESUMO
OBJECTIVE: We investigated the baseline disease-modifying antirheumatic drug (DMARD) use and post-acute sequelae of COVID-19 (PASC) risk among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: Patients with SARDs and confirmed COVID-19 infection at Mass General Brigham completed a survey ≥28 days after positive PCR/Antigen test to prospectively investigate their COVID-19 courses. We investigated DMARD use at COVID-19 onset and PASC risk. PASC was defined as any COVID-19 symptom that persisted for ≥28 days. We used logistic regression to estimate odds ratios (OR) for PASC by DMARD class. We also used restricted mean survival time to determine the difference in symptom-free days by DMARD class in the 28-day period after infection. RESULTS: We analyzed 510 patients with SARDs and COVID-19 from 11/Mar/2021-17/Jun/2023; 202 (40%) developed PASC. CD20 inhibitor (CD20i) users had significantly higher odds of developing PASC vs csDMARD users (adjusted OR 2.69, 95%CI 1.23-5.88). IL-12/23, IL-17A, or IL-23 inhibitor (IL-12/23i, IL-17Ai, IL-23i) users also had significantly higher odds of PASC (adjusted OR 3.03, 95%CI 1.08-8.49). CD20i users had significantly fewer symptom-free days vs csDMARD users (adjusted -4.12, 95%CI -7.29 to -0.94). CONCLUSION: CD20i users had significantly higher odds of PASC and fewer symptom-free days over the 28 days following COVID-19 diagnosis compared with csDMARD users. Further research is needed to investigate whether PASC risk in CD20i users may be due to prolonged infection or other immune mechanisms. The association of IL-12/23i, IL-17Ai, and IL-23i and PASC calls for additional study.
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OBJECTIVE: To investigate risk factors and outcomes of repeat COVID-19 infections among patients with systemic autoimmune rheumatic diseases (SARDs). METHODS: We performed a case-control study investigating repeat COVID-19 infection within the Mass General Brigham Health Care System. We systematically identified all SARD patients with confirmed COVID-19 (15/Mar/2020 to 17/Oct/2022). Cases had confirmed repeat COVID-19 infections >60 days apart (index date: repeat COVID-19 date). Controls were matched to cases (up to 3:1) by calendar date of first infection and duration between first COVID-19 infection and index dates. We collected demographics, lifestyle, comorbidities, SARD features, and COVID-19 characteristics at initial infection and index date by medical record review. We used conditional logistic regression to identify associations with repeat COVID-19 infection, adjusting for potential confounders. We described the severity of repeat COVID-19 infection among cases. RESULTS: Among 2203 SARD patients with COVID-19, we identified 76 cases with repeat COVID-19 infection (80.3 % female) and matched to 207 matched controls (77.8 % female) with no repeat infection. At first infection, cases were younger (mean 49.5 vs. 60.3 years, p < 0.0001), less likely to have hypertension (32.9 % vs. 45.9 %, p = 0.050), and less likely to have been hospitalized for COVID-19 (13.2 % vs. 24.6 %, p = 0.037) than controls. At index date, cases were more likely than controls to be rituximab users (18.4 % vs. 6.3 %, p = 0.0021). In the multivariable model, younger age (OR 0.67 per 10 years, 95 %CI 0.54-0.82), rituximab use vs. non-use (OR 3.38, 95 %CI 1.26-9.08), and methotrexate use vs. non-use (OR 2.24, 95 %CI 1.08-4.61) were each associated with repeat COVID-19 infection. Among those with repeat COVID-19 infection, 5/76 (6.6 %) were hospitalized and there were no deaths. CONCLUSION: Younger age, rituximab, and methotrexate were each associated with repeat COVID-19 infection risk among patients with SARDs. Reassuringly, there were no deaths, and the hospitalization rate was low among those with repeat COVID-19 infection.
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Doenças Autoimunes , COVID-19 , Doenças Reumáticas , Humanos , Feminino , Criança , Masculino , Estudos de Casos e Controles , Metotrexato , Rituximab , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , Fatores de Risco , Doenças Autoimunes/complicações , Doenças Autoimunes/epidemiologiaRESUMO
Objectives: To investigate COVID-19 breakthrough infection after third mRNA vaccine dose among patients with RA by immunomodulator drug class, and we hypothesized that CD20 inhibitors (CD20i) would have higher risk for breakthrough COVID-19 vs. TNF inhibitors (TNFi). Methods: We performed a retrospective cohort study investigating breakthrough COVID-19 among RA patients at Mass General Brigham in Boston, MA, USA. Patients were followed from the date of 3rd vaccine dose until breakthrough COVID-19, death, or end of follow-up (18/Jan/2023). Covariates included demographics, lifestyle, comorbidities, and prior COVID-19. We used Cox proportional hazards models to estimate breakthrough COVID-19 risk by immunomodulator drug class. We used propensity score (PS) overlap-weighting to compare users of CD20i vs. TNFi. Results: We analyzed 5781 patients with RA that received 3 mRNA vaccine doses (78.8% female, mean age 64.2 years). During mean follow-up of 12.8 months, 1173 (20.2%) had breakthrough COVID_19. Use of CD20i (adjusted HR 1.74, 95%CI 1.30-2.33) and glucocorticoid monotherapy (adjusted HR 1.47, 95%CI 1.09-1.98) were each associated with breakthrough COVID-19 compared to TNFi use. In the PS overlap-weighted analysis, CD20i users also had higher breakthrough COVID-19 risk than TNFi users (HR 1.62, 95%CI 1.02-2.56). A sensitivity analysis excluding patients with cancer or interstitial lung disease yielded similar findings. Conclusions: We identified CD20i and glucocorticoid monotherapy as risk factors for breakthrough COVID-19 among patients with RA after a 3rd vaccine dose. This contemporary study highlights the real-world impact of blunted immune responses in these subgroups and the need for effective risk mitigation strategies.
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Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2- or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti-SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs.
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Imunidade Humoral , Síndrome de COVID-19 Pós-Aguda , Doenças Reumáticas , SARS-CoV-2 , Doenças Reumáticas/complicações , Doenças Reumáticas/imunologia , SARS-CoV-2/imunologia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Síndrome de COVID-19 Pós-Aguda/complicações , Síndrome de COVID-19 Pós-Aguda/imunologia , Doenças Endêmicas , Receptores Fc/metabolismo , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
OBJECTIVE: IgG4-related disease (IgG4-RD), a multi-organ autoimmune disease, causes diverse manifestations that can lead to symptoms and distress. We developed and validated the Symptom Severity Index (SSI) to assess symptom burden. METHODS: A pilot SSI was tested in n = 5; several gaps were identified. Twenty semi-structured qualitative interviews were performed to expand the item set and identify missing symptoms. Subsequent changes resulted in the current SSI; it was administered with quality of life (QOL) measures to n = 136. We assessed symptom burden and the construct validity of the SSI. A distress score for each symptom is calculated by multiplying symptom frequency ("Never" [0 points] to "Every Day" [3 points]) by associated distress ("None" [0 points] to "Very Much" [4 points]). Each distress score is summed to calculate a total SSI score. RESULTS: The SSI assesses the frequency and distress of 24 symptoms. Among n = 136 with ≥ 1 SSI, 90% experienced ≥ 1 symptom and 88% had distress. The median SSI score was 6.5 (IQR 3.0, 18.0). Fear of more severe disease was observed in 49%. The SSI inversely correlated with the SF-36 (r= - 0.51, p<0.001), the feeling thermometer (r= - 0.28, p<0.001), and the EQ-5D (r= - 0.28, p<0.001). The median SSI score was higher during active vs non-active disease among n = 52 who completed >1 SSI (15 [6, 26] vs. 3 [2, 14], p = 0.008). CONCLUSIONS: Symptoms and distress are common in IgG4-RD and associated with worse health-related QOL. The SSI has face, content, and construct validity; it corresponds with QOL measures.
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Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Humanos , Qualidade de Vida , Doenças Autoimunes/diagnóstico , Medidas de Resultados Relatados pelo PacienteRESUMO
BACKGROUND: IgG4-related disease (IgG4-RD) is an immune-mediated condition that can affect nearly any organ or anatomic site. We sought to describe the epidemiology of IgG4-RD in the USA. METHODS: We used Optum's deidentified Clinformatics Data Mart Database from 1 January 2009 to 31 December 2021 to identify IgG4-RD cases using a validated algorithm. We estimated the incidence rate and prevalence between 2015 and 2019 (when rates stabilised), standardised to the US population by age and sex. We compared mortality rates among patients with IgG4-RD to the non-IgG4-RD population matched in a 1:10 ratio on age, sex, race/ethnicity and encounter date. We used Cox proportional hazards models to estimate HRs and 95% CIs. RESULTS: We identified 524 IgG4-RD cases. The mean age was 56.5 years with 57.6% female and 66% White. The incidence of IgG4-RD increased during the study period from 0.78 to 1.39 per 100 000 person-years in 2015 and 2019, respectively. The point prevalence on 1 Janury 2019 was 5.3/100 000 persons. During follow-up, there were 39 and 164 deaths among 515 IgG4-RD cases and 5160 comparators, resulting in a mortality rate of 3.42 and 1.46/100 person-years, respectively, and adjusted HR of 2.51 (95% CI 1.76 to 3.56). CONCLUSIONS: The incidence of IgG4-RD is similar to that of systemic rheumatic diseases such as ANCA-associated vasculitis and systemic sclerosis but may be increasing as familiarity with this diagnosis grows. Clinicians should be aware of this condition, especially given the excess risk of death. Identification of effective therapies is an important research agenda.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Doença Relacionada a Imunoglobulina G4 , Humanos , Adulto , Feminino , Pessoa de Meia-Idade , Masculino , Doença Relacionada a Imunoglobulina G4/diagnóstico , Incidência , Prevalência , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Imunoglobulina GRESUMO
OBJECTIVE: To compare rituximab- versus cyclophosphamide-based remission induction strategies for the long-term risks of kidney failure and death in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in a real-world cohort. METHODS: We performed a cohort study using the Mass General Brigham AAV Cohort, which includes proteinase 3-ANCA+ and myeloperoxidase (MPO)-ANCA+ AAV patients diagnosed from January 1, 2002 to December 31, 2019. We included cases in which the initial remission induction strategy was based either on rituximab or cyclophosphamide. The primary outcome was the composite outcome of kidney failure or death. We used multivariable Cox proportional hazards models and propensity score-matched analyses to assess the association of rituximab- versus cyclophosphamide-based treatment strategies with the composite outcome of kidney failure or death. RESULTS: Of 595 included patients, 352 patients (~60%) received rituximab-based and 243 patients (~40%) received cyclophosphamide-based regimens. The mean age was 61 years, 58% of patients were female, 70% of patients were MPO-ANCA+, and 69% of patients had renal involvement (median estimated glomerular filtration rate 37.3 ml/minute/1.73 m2 ). There were 133 events at 5 years, and the incidence rates in rituximab- and cyclophosphamide-based regimens were 6.8 and 6.1 per 100 person-years, respectively. The risk of kidney failure or death was similar in both groups in multivariable-adjusted analyses (hazard ratio [HR] 1.03 [95% confidence interval (95% CI) 0.55-1.93]) and in propensity score-matched analyses (HR 1.05 [95% CI 0.55-1.99]) at 5 years. Our findings were similar when outcomes were assessed at 1 and 2 years as well as in subgroups stratified according to renal involvement and severity as well as major organ involvement. CONCLUSION: Rituximab- and cyclophosphamide-based remission induction strategies for AAV are associated with similar risks of kidney failure and death.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Insuficiência Renal , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Rituximab/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Insuficiência Renal/epidemiologia , Indução de Remissão , Imunossupressores/uso terapêuticoRESUMO
OBJECTIVE: A spectrum of chronic kidney disease (CKD) and end-stage renal disease (ESRD) may occur in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). The longitudinal trajectory of renal function in AAV is poorly understood. METHODS: Patients with ≥2 creatinine measurements, including at baseline (±30 days of treatment initiation), were included from the Mass General Brigham AAV Cohort. We calculated estimated glomerular filtration rate (eGFR). We incorporated longitudinal changes in eGFR into a group-based trajectory model to identify patients with similar patterns of change in renal function. The chi-square test and the Kruskal-Wallis test were used to evaluate differences between groups in categorical variables and non-normally distributed continuous variables, respectively. RESULTS: In 255 AAV patients, we identified 4 renal trajectory groups: rapid decline (n = 20), impaired (n = 82), preserved (n = 129), and recovery (n = 24). The rapid decline and impaired groups had greater baseline comorbidity (P = 0.01) and lower prevasculitis eGFR (P = 0.02). Clinically significant CKD (eGFR <60 ml/minute/1.73 m2 ) persisted over 5 years in >75% of the impaired group, compared to <40% of patients in the preserved group (P < 0.001). ESRD occurred most frequently in the rapid decline (100%), followed by the impaired and preserved groups (7% each). Baseline AAV renal involvement was present prior to 95% of ESRD. However, ESRD etiology varied, with 90% of rapid-onset ESRD attributed to vasculitis, versus 17-44% in impaired or preserved groups (P = 0.001). CONCLUSION: We identified 4 longitudinal patterns of renal function after AAV diagnosis. Our findings highlight the burden of CKD in AAV and provide a framework for future research into personalized care in this vulnerable population.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/etiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Rim/fisiologia , Estudos RetrospectivosRESUMO
Background: Some patients with systemic autoimmune rheumatic disease and immunosuppression might still be at risk of severe COVID-19. The effect of outpatient SARS-CoV-2 treatments on COVID-19 outcomes among patients with systemic autoimmune rheumatic disease is unclear. We aimed to evaluate temporal trends, severe outcomes, and COVID-19 rebound among patients with systemic autoimmune rheumatic disease and COVID-19 who received outpatient SARS-CoV-2 treatment compared with those who did not receive outpatient treatment. Methods: We did a retrospective cohort study at Mass General Brigham Integrated Health Care System, Boston, MA, USA. We included patients aged 18 years or older with a pre-existing systemic autoimmune rheumatic disease, who had COVID-19 onset between Jan 23 and May 30, 2022. We identified COVID-19 by positive PCR or antigen test (index date defined as the date of first positive test) and systemic autoimmune rheumatic diseases using diagnosis codes and immunomodulator prescription. Outpatient SARS-CoV-2 treatments were confirmed by medical record review. The primary outcome was severe COVID-19, defined as hospitalisation or death within 30 days after the index date. COVID-19 rebound was defined as documentation of a negative SARS-CoV-2 test after treatment followed by a newly positive test. The association of outpatient SARS-CoV-2 treatment versus no outpatient treatment with severe COVID-19 outcomes was assessed using multivariable logistic regression. Findings: Between Jan 23 and May 30, 2022, 704 patients were identified and included in our analysis (mean age 58·4 years [SD 15·9]; 536 [76%] were female and 168 [24%] were male, 590 [84%] were White and 39 [6%] were Black, and 347 [49%] had rheumatoid arthritis). Outpatient SARS-CoV-2 treatments increased in frequency over calendar time (p<0·0001). A total of 426 (61%) of 704 patients received outpatient treatment (307 [44%] with nirmatrelvir-ritonavir, 105 [15%] with monoclonal antibodies, five [1%] with molnupiravir, three [<1%] with remdesivir, and six [1%] with combination treatment). There were nine (2·1%) hospitalisations or deaths among 426 patients who received outpatient treatment compared with 49 (17·6%) among 278 who did not receive outpatient treatment (odds ratio [adjusted for age, sex, race, comorbidities, and kidney function] 0·12, 95% CI 0·05-0·25). 25 (7·9%) of 318 patients who received oral outpatient treatment had documented COVID-19 rebound. Interpretation: Outpatient treatment was associated with lower odds of severe COVID-19 outcomes compared with no outpatient treatment. These findings highlight the importance of outpatient SARS-CoV-2 treatment for patients with systemic autoimmune rheumatic disease and COVID-19 and the need for further research on COVID-19 rebound. Funding: None.
RESUMO
OBJECTIVE: To compare the effectiveness of mRNA vaccines (BNT162b2 vs mRNA-1273) against coronavirus disease 2019 (COVID-19) infection among patients with systemic autoimmune rheumatic diseases (SARDs) on immunomodulatory medications. METHODS: We identified patients with SARDs being treated with disease-modifying antirheumatic drugs (DMARDs) and/or glucocorticoids in the Mass General Brigham healthcare system who received either BNT162b2 or mRNA-1273 as their initial vaccine series. Patients were followed until positive SARS-CoV-2 test, death, or February 22, 2022. We compared the risk of breakthrough infection between BNT162b2 and mRNA-1273 vaccine recipients using time-stratified, overlap propensity score (PS)-weighted Cox proportional hazard models. RESULTS: We identified 9838 patients with SARDs who received BNT162b2 or mRNA-1273. Demographic and clinical characteristics were similar in both groups after overlap weighting: mean age 61 years, 75% female, 52% with rheumatoid arthritis, 74% receiving conventional synthetic DMARDs, and 43% receiving biologic DMARDs. Of 5516 BNT162b2 and 4322 mRNA-1273 recipients, 446 and 329 had a breakthrough infection, respectively. The corresponding time-stratified PS-weighted rate difference of breakthrough infection was 0.71 (95% CI -0.70 to 2.12) per 1000 person-months with a weighted hazard ratio (HR) of 1.12 (95% CI 0.90 to 1.39). When follow-up was censored prior to the Omicron wave, there was a trend toward higher breakthrough risk with BNT162b2 vs mRNA-1273 (weighted HR 1.34, 95% CI 0.91 to 1.98). CONCLUSION: Among patients with SARDs, the risk of breakthrough COVID-19 infection is similar after receiving either BNT162b2 or mRNA-1273. Patients with SARDs initiating the vaccine series should be encouraged to receive whichever mRNA vaccine is available.
Assuntos
Antirreumáticos , Artrite Reumatoide , COVID-19 , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Vacina BNT162 , Vacina de mRNA-1273 contra 2019-nCoV , Vacinas contra COVID-19 , SARS-CoV-2 , Vacinas de mRNARESUMO
OBJECTIVE: COVID-19 patients with rheumatic disease have a higher risk of mechanical ventilation than the general population. The present study was undertaken to assess lung involvement using a validated deep learning algorithm that extracts a quantitative measure of radiographic lung disease severity. METHODS: We performed a comparative cohort study of rheumatic disease patients with COVID-19 and ≥1 chest radiograph within ±2 weeks of COVID-19 diagnosis and matched comparators. We used unadjusted and adjusted (for age, Charlson comorbidity index, and interstitial lung disease) quantile regression to compare the maximum pulmonary x-ray severity (PXS) score at the 10th to 90th percentiles between groups. We evaluated the association of severe PXS score (>9) with mechanical ventilation and death using Cox regression. RESULTS: We identified 70 patients with rheumatic disease and 463 general population comparators. Maximum PXS scores were similar in the rheumatic disease patients and comparators at the 10th to 60th percentiles but significantly higher among rheumatic disease patients at the 70th to 90th percentiles (90th percentile score of 10.2 versus 9.2; adjusted P = 0.03). Rheumatic disease patients were more likely to have a PXS score of >9 (20% versus 11%; P = 0.02), indicating severe pulmonary disease. Rheumatic disease patients with PXS scores >9 versus ≤9 had higher risk of mechanical ventilation (hazard ratio [HR] 24.1 [95% confidence interval (95% CI) 6.7, 86.9]) and death (HR 8.2 [95% CI 0.7, 90.4]). CONCLUSION: Rheumatic disease patients with COVID-19 had more severe radiographic lung involvement than comparators. Higher PXS scores were associated with mechanical ventilation and will be important for future studies leveraging big data to assess COVID-19 outcomes in rheumatic disease patients.