tbuckley/cabot-search huggingface dataset:
Socioeconomic Inequality in Respiratory Health in the US From 1959 to 2018
Authors: Adam W. Gaffney, David U. Himmelstein, David C. Christiani, Steffie Woolhandler
Journal: JAMA Internal Medicine (2021)

Air quality has improved and smoking rates have declined over the past half-century in the US. It is unknown whether such secular improvements, and other policies, have helped close socioeconomic gaps in respiratory health.To describe long-term trends in socioeconomic disparities in respiratory disease prevalence, pulmonary symptoms, and pulmonary function.This repeated cross-sectional analysis of the nationally representative National Health and Nutrition Examination Surveys (NHANES) and predecessor surveys, conducted from 1959 to 2018. included 160 495 participants aged 6 to 74 years.Family income quintile defined using year-specific thresholds; educational attainment.Trends in socioeconomic disparities in prevalence of current/former smoking among adults aged 25 to 74 years; 3 respiratory symptoms (dyspnea on exertion, cough, and wheezing) among adults aged 40 to 74 years; asthma stratified by age (6-11, 12-17, and 18-74 years); chronic obstructive pulmonary disease ([COPD] adults aged 40-74 years); and 3 measures of pulmonary function (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and FEV1/FVC<0.70) among adults aged 24 to 74 years.Our sample included 160 495 individuals surveyed between 1959 and 2018: 27 948 children aged 6 to 11 years; 26 956 children aged 12 to 17 years; and 105 591 adults aged 18 to 74 years. Income- and education-based disparities in smoking prevalence widened from 1971 to 2018. Socioeconomic disparities in respiratory symptoms persisted or worsened from 1959 to 2018. For instance, from 1971 to 1975, 44.5% of those in the lowest income quintile reported dyspnea on exertion vs 26.4% of those in the highest quintile, whereas from 2017 to 2018 the corresponding proportions were 48.3% and 27.9%. Disparities in cough and wheezing rose over time. Asthma prevalence rose for all children after 1980, but more sharply among poorer children. Income-based disparities in diagnosed COPD also widened over time, from 4.5 percentage points (age- and sex-adjusted) in 1971 to 11.3 percentage points from 2013 to 2018. Socioeconomic disparities in FEV1 and FVC also increased. For instance, from 1971 to 1975, the age- and height-adjusted FEV1 of men in the lowest income quintile was 203.6 mL lower than men in the highest quintile, a difference that widened to 248.5 mL from 2007 to 2012 (95% CI, -328.0 to -169.0). However, disparities in rates of FEV1/FVC lower than 0.70 changed little.Socioeconomic disparities in pulmonary health persisted and potentially worsened over the past 6 decades, suggesting that the benefits of improved air quality and smoking reductions have not been equally distributed. Socioeconomic position may function as an independent determinant of pulmonary health.
Clinical Implications of Pharmacogenomic Testing in the Real World—Insights From a Pediatric Program
Authors: Catherine Chanfreau-Coffinier
Journal: JAMA Network Open (2021)

Iris Cohn, MSc, RPh; Roozbeh Manshaei, PhD; Eriskay Liston, MSc; John B. A. Okello, PhD, MMIE; Reem Khan, MA; Meredith R. Curtis, BSc; Abby J. Krupski, BSc; Rebekah K. Jobling, MD; Kelsey Kalbfleisch, MSc; Tara A. Paton, PhD; Miriam S. Reuter, MD; Robin Z. Hayeems, PhD, ScM; Ruud H. J. Verstegen, MD, PhD; Aaron Goldman, PhD; Raymond H. Kim, MD, PhD; Shinya Ito, MD
AB0895-HPR A MODERATED MEDIATION ANALYSIS FOR POOR ORAL HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH BEHÇET’S DISEASE
Authors: E. N. Çakir, Y. Yenisoy, A. Kapusuz, K. Abacar, F. Alibaz-Oner, M. Yay, Ü. Karaçayli, N. Inanc, T. Ergun, H. Direskeneli, G. Mumcu
Journal: Annals of the Rheumatic Diseases (2021)

Background: Since oral ulcer is a common clinical manifestation, oral health-related quality of life (OHRQoL) is affected by the presence of oral ulcer poorly in patients with Behcet’s disease (BD). Objectives: The aim of the study was to examine associated factors for poor OHRQoL status to improve treatment outcomes in patients with BD. Methods: In this retrospective study, 339 BD patients (F/M: 179/160, mean age: 36,13±9,81 years) included. Data were collected by a structured questionnaire regarding treatment expectation, Oral Health Impact Profile-14 (OHIP-14) questionnaire for OHRQoL, oral ulcer activity, and disease severity score. Treatment expectation was coded by a 5-point Likert type scale (1: symptoms were completely cured vs 5: symptoms were worsened). OHIP-14 score was between “0 point (the best score)” and “56 points (the worst score)”. The disease severity score was calculated according to the organ involvement. Then, patients were categorised as mucocutaneous involvement (n=181) and severe organ involvement (n=158). After preliminary analysis, a Moderated Mediation analysis was carried out. Results: Oral ulcer activity was seen in 63,4% of the group (n=215). OHIP-14 score (22,05±16,47) was correlated with Treatment expectations (2,35±0,98) (r: 0,36 p=0.000) in the group. Poor scores of OHIP-14 and Treatment expectations were found in patients with active oral ulcers (mucocutaneous involvement: 27,56±14,55; 2,68±0,87, vs severe organ involvement: 28,51±17,25; 2,43±0,99) compared to those of inactive patients (mucocutaneous involvement: 13,38±12,23; 1,81±0,73 vs severe organ involvement: 8,79±10,19; 1,85±1,02) (p=0.000 for all). Patients with active oral ulcers were younger (35,09±9,52) than the others (39,57±10,06) in the mucocutaneous involvement group (p=0.0011) whereas a similar relation was not seen in the severe organ involvement (p=0.233). In the moderated mediation analysis, it was found that OHIP-14 score was increased by the presence of oral ulcer in the direct path (p=0.0000) and the negative Expectation of the treatment as a first mediator (p = 0.0001) in the indirect path. Oral ulcer activity was associated with younger patients (p=0.0039). This effect was seen especially in patients with mucocutaneous involvement that had a moderator effect (p=0.0040). In addition, age was found to be a second mediator for the poor OHIP-14 score (p = 0.0053). Mediators and the moderator were found to effective for OHIP-14 score a bootstrap analysis with 5000 replications. Conclusion: OHRQoL was affected by oral ulcer activity and poor treatment expectations. Age was also found to be another critical factor for OHRQoL. Disclosure of Interests: None declared
POS0233 THE EFFICIENCY OF TREATMENT OF COXITIS IN AXIAL SPONDYLOARTHRITIS: EXPERIENCE OF REAL CLINICAL PRACTICE
Authors: E. Agafonova, S. Erdes
Journal: Annals of the Rheumatic Diseases (2021)

Background: Standard therapy for axial spondyloarthritis (axSpA) is effective in inflammatory lesions of the axial skeleton and peripheral arthritis, but its effect on coxitis has not been studied. Objectives: To assess the effectiveness of anti-TNF therapy for coxitis in patients with axSpA. Methods: An open observational study was conducted. There were 56 patients with axSPA and coxitis for 2 years who received NSAIDs or NSAIDs+anti-TNF therapy in real clinical practice. The study included only those patients who completed a 2-year follow-up period. All patients regardless of complaints underwent X-ray examination of the pelvis, ultrasound and magnetic resonance imaging (MRI) of the hip joints. An increase in the cervical-capsular distance (CCD) of more than 7 mm and the presence of asymmetry between the joints of more than 1.5 mm were taken for coxitis on ultrasound of the hip joint. The presence of synovitis and/or osteitis was taken for coxitis on MRI. The average age was 31.1±7.0 years, with an average duration of the disease 74.5±100.1 months. HLA-B27 positive were 52 (92%) patients. Results: A comparative analysis of clinical, laboratory and other parameters of the disease was carried out against the background of 2-year follow-up of patients who were constantly taking only NSAIDs or their combination with anti-TNF therapies (Table 1). Table 1. Parametrs Group NSAIDs+ anti-TNF n=27 baseline Group NSAIDs+ anti-TNF n=27 after 2 y p Group NSAIDs n=29 baseline Group NSAIDs n=29 after 2 y p BASRI hip ≥2; n % 10 (37%) 18 (67%) &gt;0,05 6 (21%) 14 (48%) &lt;0,05 MRI coxitis; n % 27 (100%) 19 (70%) &lt;0,05 28 (97%) 24 (83%) &gt;0,05 CCDmm;Me, [25 ‰;75‰] 7,9 [7,0;8,2] 7,2 [6,1;8,3] &lt;0,05 7,2 [6,2;7,8] 6,2[5,6;7,8] &gt;0,05 CRP,mg/L; Me, [25 ‰; 75‰] 23,7[8,4;56] 6,0 [1,0;17,3] &lt;0,05 10,3 [2,9;18,6] 8,4[2,9;18,5] &gt;0,05 ESR; Me, [25 ‰; 75‰] 25 [15;38] 15,0 [5;35,2] &lt;0,05 13 [7,8;25,5] 13 [6;26,3] &gt;0,05 ASDAS CRP; Me, [25 ‰; 75‰] 3,5 [2,4;4,7] 2,0 [1,0;2,4] &lt;0,05 2,6 [1,3;3,6] 2,0[1,1;2,3] &gt;0,05 BASDAI; Me, [25‰; 75‰] 4,7[4,2;6,9] 2,2 [2,0;3,7] &lt;0,05 4,2 [2,4;5,8] 2,2[1,4;4,2] &gt;0,05 BASFI; Me,[25‰;75‰] 4,0 [2,0;6,5] 1,9 [0,9;2,9] &lt;0,05 1,2 [0,3;2,5] 0,9[0,4;2,8] &gt;0,05 Conclusion: 1. Anti-TNF+NSAIDs therapy with 2 years of use effectively controls the activity of axSpA. 2. Two-year therapy with NSAIDs in combination with anti-TNF, reduces the inflammation of hip joints in some patients according to ultrasound and MRI data. 3. The present study did not conclusively confirm that 2-year anti-TNF therapy with NSAIDs effectively prevents the progression of X-ray bursitis in axSpA. 4. Further studies are needed to improve the effectiveness of treatment of coxitis in axSpA. Disclosure of Interests: None declared.
Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology
Authors: Al B. Benson, Michael I. D’Angelica, Daniel E. Abbott, Daniel A. Anaya, Robert Anders, Chandrakanth Are, Melinda Bachini, Mitesh Borad, Daniel Brown, Adam Burgoyne, Prabhleen Chahal, Daniel T. Chang, Jordan Cloyd, Anne M. Covey, Evan S. Glazer, Lipika Goyal, William G. Hawkins, Renuka Iyer, Rojymon Jacob, R. Kate Kelley, Robin Kim, Matthew Levine, Manisha Palta, James O. Park, Steven Raman, Sanjay Reddy, Vaibhav Sahai, Tracey Schefter, Gagandeep Singh, Stacey Stein, Jean-Nicolas Vauthey, Alan P. Venook, Adam Yopp, Nicole R. McMillian, Cindy Hochstetler, Susan D. Darlow
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.
Deletion of Lats1/2 in adult kidney epithelia leads to renal cell carcinoma
Authors: Phoebe Carter, Ulrike Schnell, Christopher Chaney, Betty Tong, Xinchao Pan, Jianhua Ye, Glenda Mernaugh, Jennifer L. Cotton, Vitaly Margulis, Junhao Mao, Roy Zent, Bret M. Evers, Payal Kapur, Thomas J. Carroll
Journal: Journal of Clinical Investigation (2021)
POS0361 DNA METHYLATION SIGNATURES CHARACTERIZE PSORIASIS AND PSORIATIC ARTHRITIS IN MONOZYGOTIC TWINS DISCORDANT FOR THE DISEASE
Authors: M. Vecellio, A. Ceribelli, E. Paraboschi, N. Isailovic, F. Motta, M. De Santis, R. Asselta, S. Duga, C. Selmi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Psoriatic disease is a chronic inflammatory disorder spanning from skin disease (psoriasis) to psoriatic arthritis (PsA). The genetic background is insufficient to explain disease onset as illustrated by not very informative Genome Wide Association Studies and monozygotic (MZ) twin studies recently performed. It is strongly assumed that epigenetics may contribute to disease susceptibility modulating gene expression. DNA methylation has been found involved in several autoimmune inflammatory rheumatic diseases. Here we have analysed the DNA methylation profile of a selected cohort of MZ twins discordant for psoriasis/PsA. Objectives: To identify the methylome associated with psoriasis and PsA in the peripheral blood of MZ twins discordant for these conditions. Methods: Peripheral blood from 7 couples of MZ twins discordant for psoriatic disease was collected and DNA extracted for a genome-wide evaluation of the DNA methylation profile, with the Infinium MethylationEPIC BeadChip. Minfi and the packages of the Bioconductor were used to analyse the data obtained. Quality control and exclusion criteria were applied to the raw data having a final number of 762.451 probes, which accounts for 88% of the total. Results: The approach first identified 2564 differentially methylated positions (DMPs; *p&lt;0.005) with 19 genes potentially affected (with at least two DMPs within 1 kb of distance), including SMAD3 and SMARCA4/BRG1 involved in the Interferon and TGFβ pathways. Gene Ontology (GO) analysis of DMP-associated genes showed a significative enrichment (*p&lt;0.005) in transcription factor binding, transcription corepressor and transcription coactivator activity, SMAD binding and histone -lysine-N-methyltransferase activity. To further validate the results, 5’-methylcytosine immunoprecipitation (MedIP) followed by Real Time PCR was performed to assess the methylation level of SMAD3 and SMARCA4/BRG1 promoters in the same cohort of MZ twins. We found significantly DNA methylation enrichment in SMARCA4/BRG1 promoter in psoriatic disease twins (p&lt;0.05). SMAD3 and SMARCA4/BRG1 mRNA expression was also assessed to evaluate any inverse correlation with promoter methylation level, on the MZ cohort used for the EPIC array (n=4) and on a cohort of PsA/Ps patients (n=8) and appropriate healthy controls (n=3). Reduced mRNA expression (p&lt;0.05) was demonstrated for SMARCA4/BRG1 (n=4). Conversely, no changes were found for SMAD3. Conclusion: We report the first DNA methylation approach in MZ twins discordant for psoriatic disease. We believe that the observed changes in SMAD3 and SMARCA/BRG1 genes may suggest an epigenetic imbalance of chromatin remodelling factors involved in inflammation pathways with a potential role in PsA/psoriasis immunopathogenesis. Disclosure of Interests: None declared
AB0058 ASSOCIATION BETWEEN HLA-DRB1*04:01, RHEUMATOID NODULES AND PARTICULAR EPITOPES OF CITRULLINATED FIBRIN IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: G. Larid, M. Pancarte, G. Offer, C. Clavel, M. Martin, V. Pradel, I. Auger, P. Lafforgue, G. Serre, J. Roudier, N. Balandraud
Journal: Annals of the Rheumatic Diseases (2021)

Background: Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding the shared epitope (SE), a 5 amino acid motive. RA is usually preceded by the emergence of anti-citrullinated protein antibodies (ACPAs) detected by anti-CCP2 tests. Citrullin is a neutral amino acid resulting from post translational modification of arginin by Peptidyl Arginyl Deiminases (PADs). ACPAs recognize epitopes from citrullinated human fibrinogen (Fib-cit) and can be specifically detected by the AhFibA assay. Five peptides derived from Fib-cit together represent almost all of the epitopes recognized by patients with ACPA-positive RA: β60–74cit, α36–50cit, α621–635cit, α501–515cit and α171–185cit. As RA is a pleiomorphic disease, whose evolution is difficult to predict, the use of antibody fine specificity as a marker of clinical phenotypes has become a major challenge. Objectives: Our objective was to study whether clinical characteristics and HLA-DRB1 genetic background were associated with a specific reactivity against these epitopes. Methods: 184 ACPA positive RA patients fulfilling the 2010 ACR/EULAR criteria were studied. Patients characteristics, including HLA-DRB1 genotype, were collected from their medical files. Anti-CCP2, AhFibA, Rheumatoid Factors (RF), and antibodies against the five major Fib-cit peptides were analyzed using ELISA assays. Results: Anti-CCP2 and AhFibA titres were strongly correlated (rs: 0.7037; p = 5.69x10 -29 , Pearson’s). Anti-α505-515cit antibodies were associated with HLA-DRB1*04:01 (OR = 5.52 [2.00 – 13.64]; p = 0.0003). High level anti-α505-515cit antibodies were significantly associated with rheumatoid nodules (OR = 2.71 [1.00 – 7.16], p= 0.044). Anti α501–515cit antibodies were associated with RF (OR=2.31 [1.10 – 4.78], p= 0.026). Conclusion: Immune complexes containing anti-α501–515cit antibodies and rheumatoid factors might be involved in the development of rheumatoid nodules on the HLA-DRB1*04:01 background. These findings highlight the role played by the HLA-DRB1*04:01 molecule and its rapid intracellular route into the lysosomes, enabling original antigen processing. Finally, purifying these epitope specific antibodies might be a new therapeutic opportunity for rheumatoid nodules. Disclosure of Interests: None declared
POS0831 EARLY INFECTIOUS RISK IN PATIENTS WITH NEWLY-DIAGNOSED ANTI-NEUTROPHILCYTOPLASMIC ANTIBODY-ASSOCIATED VASCULITIS ACCORDING TO THE REMISSION-INDUCTIONTHERAPY: A FRENCH MONOCENTRIC RETROSPECTIVE STUDY INCLUDING 145 PATIENTS
Authors: M. Gérard, H. De Boysson, R. Morello, N. M. Silva, A. C. Leroux, A. Dumont, G. Maigné, J. Boutemy, K. Khoy, D. Mariotte, T. Lobbedez, A. Aouba, S. Deshayes
Journal: Annals of the Rheumatic Diseases (2021)

Background: Few comparative data exist on early infections secondary to remission-induction therapy (RIT) with rituximab versus cyclophosphamide in newly-diagnosed ANCA-associated vasculitis (AAV) patients. Objectives: We compared and analyzed the rate and predictors of severe infections in such patients within the first six months following RIT. Methods: We included, from the databases of Caen University Hospital, all consecutive adults newly-diagnosed with granulomatosis with polyangiitis or microscopic polyangiitis between January 2006 and December 2019. We compared the survival without severe infections (WSI) and the survival without infection of any severity (WIOAS) within 6 months from the RIT, and used a multivariate cox analysis to identify predictors of infection. Results: We included 145 patients, 27 in rituximab group and 118 in cyclophosphamide group. Patients in the rituximab group more frequently had pneumococcal vaccination (p&lt;0.01) and creatinine level &lt;150 µmol/L, while other characteristics, including Birmingham Vasculitis Activity Score, were comparable between both groups. Overall, 37 severe infections and 65 infections of any severity were recorded. The survival WSI was similar in both groups (p=0.69), but survival WIOAS was lower in rituximab group (p=0.005). In multivariate analysis, risk factors at diagnosis for severe infections were chronic urinary tract disease, dialysis and absence of prophylaxis with trimethoprim-sulfamethoxazole (p&lt;0.01 each). Conclusion: The survival WIS within the 6 months following RIT was similar in patients with newly-diagnosed AAV treated by rituximab or cyclophosphamide, but survival WIOAS appeared to be lower within the 6 months following rituximab despite a better pneumococcal vaccination coverage. Figure 1. Comparison of the 6-month survival without severe infection (A) or without infection of any severity (B) in patients with newly-diagnosed ANCA-associated vasculitis treated by rituximab or cyclophosphamide Disclosure of Interests: None declared
POS0055 SARS-COV-2 OUTBREAK IN AUTOIMMUNE DISEASES: THE EURO-COVIMID STUDY
Authors: D. Saadoun, M. Vieira, M. Vautier, X. Baraliakos, I. Andreica, J. A. P. Da Silva, M. Sousa, M. Luis, N. Khmelinskii, J. M. Alvaro-Gracia, I. Castrejon, J. C. Nieto González, C. A. Scirè, E. Silvagni, A. Bortoluzzi, H. Penn, S. Hamdulay, P. Machado, B. Fautrel, P. Cacoub, M. Resche-Rigon, L. Gossec
Journal: Annals of the Rheumatic Diseases (2021)

Background: Coronavirus disease 2019 (COVID-19), has raised several questions in patients with immune-mediated inflammatory diseases (IMID). Whether the seroprevalence and factors associated with symptomatic COVID-19 are similar in IMID patients and in the general population is still unknown. Objectives: To assess the serological and clinical prevalence of COVID-19 in European IMID patients, along with the factors associated with its risk and the impacts the pandemic had on the IMID management. Methods: Prospective multicentre cross-sectional study among patients with five IMID (i.e. systemic lupus erythematous, Sjögren’s syndrome, rheumatoid arthritis, axial spondylarthritis or giant cell arteritis) from six tertiary-referral centers from France, Germany, Italy, Portugal, Spain and United Kingdom. Demographics, comorbidities, IMID, treatments, flares and COVID-19 details were collected. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests were systematically performed. Results: Between June 7 and December 8, 2020, 3028 patients were included (median age 58 years, 73.9% females). SARS-CoV-2 antibodies were detected in 166 (5.5%) patients. Symptomatic COVID-19 was seen in 122 patients (prevalence: 4.0%, 95% CI 3.4-4.8%); 23 (24.2%) of them were hospitalized and four (3.2%) died. In multivariate logistic regression analysis, symptomatic COVID-19 was more likely to be observed in patients with higher levels of C-reactive protein (OR: 1.18; 95% CI 1.05-1.33; p = 0.006), and increased with the number of IMID flares (OR: 1.27; 95% CI 1.02-1.58; p = 0.03). Conversely, it was less likely to occur in patients treated with biological therapy (OR: 0.51; 95% CI 0.32-0.82; p = 0.006). During the pandemic, at least one self-reported disease flare was seen in 654 (21.6%) patients. Also, 519 (20.6%) patients experienced changes in their treatment, with 125 of these (24.1%) being due to COVID-19. Conclusion: The SARS-CoV-2 prevalence in IMID patients over the study period seems to be similar to that of the general population 1 . The IMID inflammatory status seems to be independently associated with the development of COVID-19. References: [1]Pollán M, Pérez-Gómez B, Pastor-Barriuso R, Oteo J, Hernán MA, Pérez-Olmeda M, et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet Lond Engl. 2020 Aug 22;396(10250):535–44. Disclosure of Interests: None declared.
Modifications to residential neighbourhood characteristics and risk of 79 common health conditions: a prospective cohort study
Authors: Mika Kivimäki, G David Batty, Jaana Pentti, Solja T Nyberg, Joni V Lindbohm, Jenni Ervasti, Carlos Gonzales-Inca, Sakari B Suominen, Sari Stenholm, Pyry N Sipilä, Payam Dadvand, Jussi Vahtera
Journal: The Lancet Public Health (2021)

Observational studies have identified a link between unfavourable neighbourhood characteristics and increased risk of morbidity, but it is unclear whether changes in neighbourhoods affect future disease risk. We used a data-driven approach to assess the impact of neighbourhood modification on 79 health outcomes.