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  • 11
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 902.2-903
    Abstract: Positivity of dense fine speckles antibodies (anti-DFS70) has been associated with antinuclear antibodies positivity in people with no evidence of systemic autoimmune disease. They could be useful to distinguish patients with these characteristics that do not meet diagnostic and/or classifying criteria for any systemic autoimmune disease (SAD). Objectives: To evaluate the use of anti- DFS70 in patients with suspicion of SAD. Methods: A cross-sectional observational study was conducted at 2 tertiary-level hospitals. We included a cohort of patients visited in the last year by either rheumatology or other specialties, under suspicion of SAD, in which the IgG isotype anti-DFS70 was obtained by recombination with the Euroline Immunoblot of Euroimmun. Demographic, clinical and immunological variables were collected. Results: 102 patients (78% women) were included, median age of 49 years old. The descriptive statistics are summarized in Table 1. All patients had ANA titters 〉 1/80. 37% were positive for anti-DFS70, with homogeneous, speckled and other patterns in 36%, 72% and 15% respectively.74% were visited by rheumatologists under the suspicion of systemic lupus erythematosus (SLE) in 27%, other SAD 25%, arthralgia 36% and fibromyalgia 12%. 13% presented high DNA titters, low C3/C4 levels in 14% and 9%. SLE’s symptoms were: arthritis 21%, arthralgia 41%, cutaneous 20% and oral ulcers 8%. Anti-DFS70(+) was related to the speckled pattern in 46% compared to other patterns (p=0,009), which had a negative association with anti-DFS70(p=0,003). Regarding the diagnoses, there was a negative association with SLE, other SAD and other rheumatologic diagnoses in 88%, 75% and 55% respectively(p=0,006). Anti-DFS70(-) was associated with oral ulcers (p=0,024), decreased C3/C4 levels (p=0,007/p=0,018), psoriatic arthritis (p=0,024) and cutaneous lupus (p=0,008), but not with drug-induced SLE (p=0,48) or lupus nephritis (p=0,067). There was no statistical significance between anti-DFS70(+) and arthralgia or fibromyalgia, but these patients don’t have a SAD diagnosis. Table 1. RHEUMATOLOGY (n=75) OTHER SPECIALTIES (n=27) antiDFS70(+) n=25(100%) antiDFS70(-) n=50(100%) antiDFS70(+) n=13(100%) antiDFS70(-) n=14(100%) Women 20(80) 43(86) 8(62) 9(64) Age years (ED) 47,1 (±20,1) 50,4 (±15,5) 45,1(±26,7) 54,7(±15,6) ANA Homogeneous 8(32) 23(46) 2(15) 4(29) Pattern Speckled 22(88)* 30(60) 12(92) 9(64) IIF Other 0 10(20) 1(8) 4(29) Final diagnosis Arthralgia 12(48) 15(30) Speciality Fibromyalgia 3(12) 6(12) Dermatology 4(31) 7(49) Drug-induced SLE 2(8) 2(4) Gastroenterology 3(23) 3(21) SLE 3(12) 17(34)* Hematology 1(8) 2(14) Cutaneous lupus 0 8(16)* Other 5(38) 2(14) PsA 0 6(12)* Other 6(25) 16(32) SLE Arthritis 3(12) 13(26) Arthralgia 13(52) 18(36) Cutaneous 3(12) 12(24) Oral ulcers 0(0) 6(12)* Leukopenia 0(0) 4(8) Thrombocytopenia 0(0) 1(2) Fever 1(4) 1(2) Pleuritis 0(0) 1(2) Pericarditis 0(0) 1(2) Nephritis 0(0) 4(8) Myositis 1(4) 0(0) ANA (antinuclear antibody), IIF (indirect immunofluorescence), SLE (systemic lupus erythematosus), PsA (psoriatic arthritis), *p 〈 0, 05. Conclusion: Our results suggest that patients with suspicion of SAD, especially SLE, presented a greater proportion of negative anti-DFS70 compared to other diagnoses, including SAD, along with a decrease in complement levels and the presence of oral ulcers, being useful at the initial study of these patients. More studies are needed to characterize this association. Disclosure of Interests: Jose Luis TANDAIPAN JAIME: None declared, Berta Magallares: None declared, Julia Bernardez: None declared, ELENA RIERA ALONSO: None declared, FRANCISCO PUJALTE: None declared, Laura Martínez-Martínez: None declared, ANDRES BAUCELLS: None declared, Ivan Castellví Consultant of: Boehringer Ingelheim, Actelion, Kern Pharma, Speakers bureau: Boehringer Ingelheim, Actelion, Bristol-Myers Squibb, Roche, Hector Corominas: None declared, Silvia Martinez Pardo: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 12
    In: Journal of Neurology, Neurosurgery & Psychiatry, BMJ, Vol. 84, No. 6 ( 2013-06-01), p. 666-673
    Type of Medium: Online Resource
    ISSN: 0022-3050
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2013
    detail.hit.zdb_id: 1480429-3
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  • 13
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 74, No. Suppl 2 ( 2015-06), p. 1167.3-1167
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2015
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  • 14
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 199.1-199
    Abstract: Incidence of clinical fractures in rheumatoid arthritis (RA) is not as well-known as hip or vertebral fracture incidence. Objectives: 1. To estimate the incidence of clinical fragility fractures in a population of postmenopausal women diagnosed with RA and compare it with that of the general population; 2. To analyze the risk factors for fracture. Methods: 330 postmenopausal women with RA from 19 Spanish Rheumatology Departments, randomly selected from the registry of RA patients in each center. The control group consisted of 660 Spanish postmenopausal women from the Camargo Cohort. Clinical fractures during the previous 5 years were recorded. Assessed risk factors for fracture were: sociodemographic characteristics, BMD and variables related to RA. Results: Median age of RA patients was 64 yrs. vs. 63 yrs. in controls (ns). Evolution of the disease was 8 yrs. 78% and 76% had RF and ACPA+, respectively. 69% of patients were in remission or low activity. 85% had received glucocorticoids and methotrexate and 40% at least one biological DMARD. We identified 105 fractures (87 fragility and 18 traumatic) in 75 patients. Fifty-four patients and 47 controls had at least one major fracture (MF) (p 〈 0.001). Incidence of MF was 3.55 per 100 patient-year in patients and 0.72 in controls. Risk factors for MF in RA patients were age, previous fracture, parental hip fracture, postmenopausal period, hip BMD and cumulative dose of glucocorticoids. In controls, risk factors were age, age at menopause and lumbar BMD. Among RA-associated factors, MFs were associated with erosions, disease activity and disability. Previous fracture in RA patients was a strong risk for MF (HR: 10.37 [95% CI: 2.95-36.41]). Conclusion: Between 3 and 4 of every 100 postmenopausal women with RA have a major fracture per year, four times more than the general population. Disease activity and disability associated with RA, the cumulative dose of glucocorticoids and mainly previous fracture are associated with the development of fragility fractures. References: None Acknowledgments: Funded in part by ISCIII (PI18/00762) that included FEDER funds from the EU. Disclosure of Interests: Carmen Gómez Vaquero: None declared, Jose Manuel Olmos: None declared, J. Luis Hernández: None declared, Dacia Cerda: None declared, Cristina Hidalgo: None declared, JA Martínez López: None declared, Luis Marcelino Arboleya Rodríguez: None declared, Javier Aguilar del Rey: None declared, Silvia Martinez Pardo: None declared, Inmaculada Ros: None declared, Xavier Surís: None declared, Dolors Grados Canovas: None declared, Chesús Beltrán Audera: None declared, Evelyn Suero-Rosario: None declared, Inmaculada Gómez Gracia: None declared, Asunción Salmoral: None declared, Irene Martín-Esteve: None declared, Helena Florez: None declared, Antonio Naranjo Grant/research support from: amgen, Consultant of: UCB, Speakers bureau: AMGEN, Santos Castañeda: None declared, Soledad Ojeda Speakers bureau: AMGEN, LILLY, GEBRO, S García Carazo: None declared, Alberto García-Vadillo: None declared, Laura López Vives: None declared, À Martínez-Ferrer: None declared, Helena Borrell Paños: None declared, Pilar Aguado: None declared, Raul Castellanos-Moreira: None declared, Cristian Tebé: None declared, Núria Guañabens: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 15
    In: Journal of Medical Genetics, BMJ, Vol. 60, No. 7 ( 2023-07), p. 644-654
    Abstract: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving ANKRD11 cause KBG syndrome, but no genotype–phenotype correlation has been reported. Methods 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire. Manifestations present in 〉 50% of the patients and a ‘phenotypical score’ were used to perform a genotype–phenotype correlation in 340 patients from our cohort and the literature. Results Neurodevelopmental delay, macrodontia, triangular face, characteristic ears, nose and eyebrows were the most prevalentf (eatures. 82.8% of the patients had at least one of seven main comorbidities: hearing loss and/or otitis media, visual problems, cryptorchidism, cardiopathy, feeding difficulties and/or seizures. Associations found included a higher phenotypical score in patients with sequence variants compared with CNVs and a higher frequency of triangular face (71.1% vs 42.5% in CNVs). Short stature was more frequent in patients with exon 9 variants (62.5% inside vs 27.8% outside exon 9), and the prevalence of intellectual disability/attention deficit hyperactivity disorder/autism spectrum disorder was lower in patients with the c.1903_1907del variant (70.4% vs 89.4% other variants). Presence of macrodontia and comorbidities were associated with larger deletion sizes and hand anomalies with smaller deletions. Conclusion We present a detailed phenotypical description of KBG syndrome in the largest series reported to date of 67 patients, provide evidence of a genotype–phenotype correlation between some KBG features and specific ANKRD11 variants in 340 patients, and propose updated clinical diagnostic criteria based on our findings.
    Type of Medium: Online Resource
    ISSN: 0022-2593 , 1468-6244
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2023
    detail.hit.zdb_id: 2009590-9
    SSG: 12
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  • 16
    In: BMJ Open, BMJ, Vol. 10, No. 1 ( 2020-01), p. e029642-
    Abstract: Acute myeloblastic leukaemia (AML) constitutes the second most common haematological malignancy in the paediatric population. Current treatment regimens are based on the administration of polychemotherapy, combining high doses of cytarabine with anthracyclines and topoisomerase inhibitors. Allogeneic haematopoietic stem cell transplantation (HSCT) is an option for high-risk patients with AML (and for intermediate-risk patients if a sibling donor is available). With this strategy, AML survival has increased substantially; however, it has remained stagnant at approximately 60%, with relapse being the principal culprit. The predominant role of the immune system and natural killer (NK) cells in controlling paediatric AML has gained importance within the context of HSCT. In this protocol, we propose incorporating this cell therapy as an adjuvant treatment through the infusion of activated and expanded haploidentical NK (NKAE) cells in paediatric patients with AML who are in cytological remission after completing consolidation therapy, and with no indication for HSCT. Methods and analysis Patients up to 30 years of age, diagnosed with AML, in their first cytological remission, who have completed both the induction and the consolidation phases of chemotherapy and do not meet the criteria for allogeneic HSCT are eligible. The patients will receive two doses of NKAE cells once a week, using a GMP K562-mbIL15-41BBL stimulus from a haploidentical donor and interleukin 2 subcutaneously. The patients will then be followed up for 36 months to assess the primary endpoint, which is the probability of relapse after NK cell infusion. Ethics and dissemination This clinical trial was approved by the Clinical Research Ethics Committee of La Paz University Hospital and The Spanish Agency of Medicines and Medical Devices. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. Trial registration number EudraCT code: 2015-001901-15, ClinicalTrials.gov Identifier: NCT02763475 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 17
    In: BMJ Open, BMJ, Vol. 10, No. 10 ( 2020-10), p. e040316-
    Abstract: The evidence currently available from enhanced recovery after surgery (ERAS) programmes concerns their benefits in the immediate postoperative period, but there is still very little evidence as to whether their correct implementation benefits patients in the long term. The working hypothesis here is that, due to the lower response to surgical aggression and lower rates of postoperative complications, ERAS protocols can reduce colorectal cancer-related mortality. The main objective of this study is to analyse the impact of an ERAS programme for colorectal cancer on 5-year survival. As secondary objectives, we propose to analyse the weight of each of the predefined items in the oncological results as well as the quality of life. Methods and analysis A multicentre prospective cohort study was conducted in patients older than 18 years of age who are scheduled to undergo surgery for colorectal cancer. The study involved 12 hospitals with an implemented enhanced recovery protocol according to the guidelines published by the Spanish National Health Service. The intervention group includes patients with a minimum implementation level of 70%, and the control group includes those who fail to reach this level. Compliance will be studied using 18 key performance indicators, and the results will be analysed using cancer survival indicators, including overall survival, cancer-specific survival and relapse-free survival. The time to recurrence, perioperative morbidity and mortality, hospital stay and quality of life will also be studied, the latter using the validated EuroQol Five questionnaire. The propensity index method will be used to create comparable treatment and control groups, and a multivariate regression will be used to study each variable. The Kaplan-Meier estimator will be used to estimate survival and the log-rank test to make comparisons. A p value of less than 0.05 (two-tailed) will be considered to be significant. Ethics and dissemination Ethical approval for this study was obtained from the Aragon Ethical Committee (C.P.-C.I. PI20/086) on 4 March 2020. The findings of this study will be submitted to peer-reviewed journals ( BMJ Open, JAMA Surgery, Annals of Surgery , British Journal of Surgery ). Abstracts will be submitted to relevant national and international meetings. Trial registration number NCT04305314 .
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 18
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 74, No. Suppl 2 ( 2015-06), p. 1098.1-1098
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    RVK:
    Language: English
    Publisher: BMJ
    Publication Date: 2015
    detail.hit.zdb_id: 1481557-6
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  • 19
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 81, No. Suppl 1 ( 2022-06), p. 1287.2-1288
    Abstract: The risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) is higher than individuals from the general population. This excess risk might be explained by the chronic inflammation. Objectives To assess the Cardiovascular Risk (CV) in Rheumatoid Arthritis (RA) patients using the Framingham Score, SCORE (systematic coronary risk evaluation) and carotid ultrasound additionally to the traditional cardiovascular risk factors. Methods A single center case control study was performed. Inclusion criteria were adult RA patients (cases) and matched healthy adults in terms of age, sex, and CV risk factors (controls). Population over 75 years old, patients with established CV disease and/or stage III chronic kidney disease were excluded. Controls with other inflammatory diseases, pregnant women or any malignancy were also excluded. This study was performed from July-2019 to January-2020. The US study included presence of plaques, plaque number and measurement the intima-media thickness in both right and left carotid. Scores were multiplicated x1.5 according to EULAR recommendations. Results Overall, a total of 200 cases and 111 healthy controls were included in the study. Demographical and clinical variables were comparable between cases and controls and are shown in Table 1. In both groups a relationship between age, BMI and high blood pressure was detected (p 〈 0.001). RA patients had a Disease duration of 18.93 years (11.36); 163 (81.5%) Erosions (X-Ray of hands/feet), Extra-articular symptoms 44 (22%), Prednisone use 103 (51.5%) with Median dose of Prednisone last year 2.34 (2.84). In treatment with Methotrexate 104 (52%), bDMARDs 89 (44.5%) and JAK inhibitor 26 (13%). US study revealed a higher IMT in both right and left carotid arteries with greater presence of plaques in patients than in controls (CI 95% [1.542; 3.436], p 〈 0.001). Plaques were found in both carotid arteries in the 32% of cases and 9.91% of controls. The longer duration of RA was related to a higher presence of carotid plaques (95% [1.015; 1.056], p 〈 0.001). US and blood test results are shown in Table 3. SCORE and Framingham correlated with the CV estimation with US (p 〈 0.001), however, seemed to underestimate the global findings in cases (p 〈 0.001). Table 1. Demographic, clinical characteristics, Ultrasound Results, SCORE and Framingham of patients and controls. Characteristic RA cases n=200 Healthy controls n=111 Age - years 62.05 (10.75) 58.3 (12.14) Female sex – number (%) 163 (81.5) 73 (65.77) BMI – value (ds) 26.38 (5.03) 26.2 (5.19) Smoking habit Never Smoked 107 (53.5%) 71 (63.96%) Ex-smoker 51 (25.5%) 20 (18.02%) Active smoker 42 (21%) 20 (18.2%) Race – number (%)Caucasian 186 (93) 62 (93.94) Comorbidities – number (%) High blood pressure 83 (41.5%) 34 (30.63%) Dyslipemia 93 (46.5%) 39 (35.14%) Blood pressure -- mmHg 127.2(18.36)/78.67(10.21) 127.77(19.42)/78.28 (10.59) Ultrasound findings Right carotid cIMT 0.78 (0.15) 0.62 (0.11) Left carotid cIMT 0.77 (0.14) 0.64 (0.12) Plaques 101 (50.5%) 32 (28.83%) Bilateral 64 (32%) 11 (9.91%) Right carotid 17 (8.5%) 7 (6.31%) Left carotid 20 (10%) 14 (12.61%) SCORE Very Hihg 13 (6.5%) 5 (4.5%) High 31 (15.5%) 15 (13.51%) Low 156 (78%) 91 (81.98%) Framingham High 76 (38%) 33 (29.7%) Low 124 (62%) 78 (70.3%) Conclusion Cardiovascular risk calculators such as Framingham and SCORE are useful in RA risk estimation. However, those tools may underestimate the real risk, so carotid US might be valuable. Disclosure of Interests None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2022
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  • 20
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 80, No. Suppl 1 ( 2021-06), p. 904.1-904
    Abstract: As of the 25th of January 2021, more than 150 thousand deaths as consequence of COVID-19 have been reported in Mexico [1]. Advanced age, male gender and comorbidities have been described as risk factors for severe disease and mortality in general population [2] . COVID-19 mortality in Mexican patients with rheumatic and musculoskeletal diseases (RMDs) is unknown. Objectives: To describe characteristics of Mexican patients with RMDs and COVID-19, and to analyse factors associated with mortality. Methods: The Global Rheumatology Alliance COVID-19 (GRA) physician reported registry, is an international effort to collect information on COVID19 in adult patients with RMDs. GRA is an observational registry. The first patient from Mexico was registered on April 17, 2020. All Mexican patients registered in GRA until October 30, 2020 were included in this analysis. The association of mortality with demographic and clinical variables was estimated using logistic regression analysis. Results: A total of 323 patients were registered, with a median age of 52 (IQR 41-61) years old, 166 (51.4%) patients lived in Mexico City. The most frequent RMDs were rheumatoid arthritis, 149 (46.1%) and systemic lupus erythematosus, 24 (19.8%). Over a third of patients with RMDs and COVID-19 (119 (36.8%)) were hospitalized, and 43 (13.3%) died. Table 1 shows clinical and demographic characteristics. In the univariable analysis, the absence of comorbidities was a protective factor, OR 0.3 (95% CI 0.1-0.6). Factors associated with mortality at COVID-19 diagnosis were age over 65 years old, having type 2 diabetes, chronic renal insufficiency, treatment at COVID-19 diagnosis with corticosteroids or with CD20 inhibitors. In the multivariable adjusted analysis, these factors remained independently associated with mortality. No associations with other treatments or comorbidities at COVID-19 diagnosis were found. Conclusion: Mexican patients with RMDs and COVID-19 in the GRA physician reported registry had a mortality of 13.3%. Factors associated with mortality were those described in the general population, such as older age and being on corticosteroids and CD20 inhibitors treatment at COVID-19 diagnosis. References: [1]WHO. Coronavirus disease (COVID-19) pandemic. https://www.who.int/emergencies/diseases/novel-coronavirus-2019 . (accessed 26 January, 2021). [2]Zhou F, et al. Lancet 2020; 395 (10229):1054-62. Table 1. Clinical and demographic characteristics of patients with rheumatic diseases and COVID-19 in Mexico and mortality. Characteristics at COVID-19 diagnosis Total N=323 Death 43 (13.3) Survivors 280 (86.7) Univariable OR (95% CI) Multivariable OR (95% CI) Women, n(%) 268 (82.9) 33 (76.7) 235 (83.9) 0.6 (0.3-1.4) 0.5 (0.2-1.3) Age 〉 65 years old, n(%) 62 (19.2) 18 (41.9) 44 (15.7) 3.9 (1.9-7.7 ) 3.9 (1.9-8.3 ) RMDs* n(%) - Rheumatoid arthritis 149 (46.1) 23 (53.5) 126 (45.0) 1.6 (0.7-3.7) - Systemic Lupus Erythemathosus 64 (19.8) 10 (23.3) 54 (19.3) 1.6 (0.6-4.3) - Spondyloarthritis (axial and others) 33 (10.2) 2 (4.7) 31 (11.1) 0.1 (0.1-2.8) - Others 77 (23.8) 8 (18.6) 69 (24.6) 1 - Moderate/High disease activity 1 , n(%) 57 (18.6) 7 (17.9) 50 (18.7) 1.0 (0.4-2.5) - None comorbidities, n(%) 136 (42.1) 8 (18.6) 128 (45.7) 0.3 (0.1-0.6 ) - Hypertension*, n(%) 88 (27.2) 12 (27.9) 76 (27.1) 1.0 (0.5-2.1) - Type 2 Diabetes*, n(%) 49 (15.2) 13 (30.2) 36 (12.9) 2.9 (1.4-6.1 ) 2.4 (1.1-5.4 ) Obesity*, n(%) 21 (6.5) 3 (6.9) 18 (6.4) 1.1 (0.3-3.9) - Chronic obstructive pulmonary disease*, n(%) 15 (4.6) 1 (2.3) 14 (5.0) 0.5 (0.1-3.5) - Chronic renal insufficiency*, n(%) 17 (5.2) 6 (13.9) 11 (3.9) 3.9 (1.4-11.4 ) 3.4 (1.1-10.4 ) Cardiovascular diseases*, n(%) 14 (4.3) 2 (4.7) 12 (4.3) 1.1 (0.2-5.0) - Corticosteroids*, n(%) 171 (52.9) 30 (69.7) 141 (50.3) 2.3 (1.1-4.5 ) 3.0 (1.4-6.5 ) CsDMARD*, n(%) 247 (76.5) 33 (16.3) 214 (76.4) 1.0 (0.5- 2.2) - CD20 inhibitor*, n(%) 21 (6.5) 7 (16.3) 14 (5.0) 3.7 (1.4-9.9 ) 4.9 (1.7-14.5 ) *Overlapped, 1 307 patients. Disclosure of Interests: None declared
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Publisher: BMJ
    Publication Date: 2021
    detail.hit.zdb_id: 1481557-6
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