58 results on '"C. Diaz Torne"'
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2. AB0310 STUDY 'AR-CAT INICI': MANAGEMENT OF EARLY RHEUMATOID ARTHRITIS IN CATALONIA
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C. Perez-Garcia, J. Rovira Aguilar, L. Mateo, J. A. Gómez-Puerta, M. Valls Roc, G. Salvador Alarcon, R. Morlà, S. Holgado Pérez, C. Diaz-Torne, M. Sallés Lizarzaburu, C. García Gomez, S. Castro, N. Montala Palau, H. Borrell Paños, S. Mínguez, M. Lopez Lasanta, V. Ruiz-Esquide, C. Pitarch Grau, N. Busquets-Pérez, H. Corominas, A. Garcia Guillen, S. Rodriguez-Muguruza, M. Martínez-Morillo, and R. Sanmartí
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundGiven the progressive change in the management of inflammatory diseases,an observational study was conducted on the management of Early Rheumatoid Arthritis (ERA) in Catalonia.ObjectivesTo know the management of ERA in Catalonia, to assess whether the recommendations of the EULAR/ACR guidelines are followed and to study the causes of management variability,to set improvement objectives.MethodsAn observational,descriptive,and cross-sectional study was conducted,with data collection from June 15 to 30, 2021.The rheumatologists’ partners of the Catalan Society of Rheumatology were the object of study. An online survey was conducted with 304 members on the management of the ERA. Variables related to the characteristics of the respondents,the derivation and variables of the disease including clinical variables,type of treatment and outcomes used for follow-up including the impact of the SARS-CoV2 pandemic were included.The univariate study was performed using a study of proportions with Pearson’s correlation.ResultsA total of 105 members (34.5%) responded to the survey.11.6%>60 y, only 7.8% Characteristics of ERA:77.5% are derived from primary care(PC),52% have been between 6 weeks,42.1%>3 months.54.9% make a first visit within 2-4 weeks of PC referral and 14.7%> 8 weeks.100%provide previous analysis,only 47% had had RX performed.98% were previously treated(50.4%NSAIDs + CG,36.1%NSAIDs,12.3% CG).4.3% had GC doses>10 mg/day,11.3%> to 20mg/day.The treatment:DMARDs of choice in 100% is MTX,44.1% start doses of 10mg/week and 3.9%7.5 mg/week.The route of choice is oral(55.9% vs 44.1%).92.2% associate GC and 31.7% have not withdrawn them after 6 m.57.8% consider the maximum of MTX 25mg/W.87.1% use dosesPROs(HAQ 83.3%,RAPID 3 14.3%).The use of systematic ultrasound is collected in 33%, being himself who performs it in 59.9% and an expert rheumatologist in 46.1%.Finally, when asked about incidence of pandemic in the follow-up,53.3% consider that it is doing the same as before. 46.1% consider that telephone visits are not suitable for the follow-up of the ERAvs14.7% who consider that Yes.When questioning the situations in which they consider them to be appropriate,75.9% that it was adequate in the control after the beginning of the DMARDs.Regarding the treatment of ERA, 66% delayed the onset of biological DMARDs, 72.1% due to difficulty of follow-up and only 8.8% due to an increased risk of infection. When performing the univariate analysis, it is evident that having a monographic dispensary is associated with earlier onset of MTX(p< 0.001)and at doses≥15 mg/W(p = 0.05),greater nursing intervention(p< 0.001),greater use of PROs(p = 0.008)and there is a tendency to a shorter waiting time for first visits(p = 0.07).It is also associated with not considering telephone visits(p< 0.001), making them in less than 25%(p< 0.0001).Similarly,hospital level is directly proportional to initiation at higher doses of MTX(p< 0.0001),lower use of GCConclusionThe recommendations of EULAR/ACR in the treatment and follow-up of ERA are consistently followed,although the wide use of MTX orally is striking.It is evident that the variable that most influences the early onset of FAME and at higher doses,is a monographic dispensary,as well as greater presence of nursing and performance of PROs.AcknowledgementsThanks to all the members of the Catalan society of reuamtology who participated in the surveyDisclosure of InterestsNone declared
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- 2022
3. POS1439 CANCER IN PATIENTS WITH RHEUMATIC DISEASES EXPOSED TO DIFFERENT BIOLOGIC AND TARGETED SYNTHETIC DMARDS IN REAL-WORLD CLINICAL PRACTICE: DATA FROM A MULTICENTER REGISTER
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I. Castrejon, J. Molina Collada, C. Perez-Garcia, P. Vela-Casasempere, C. Diaz-Torne, C. Bohórquez, J. M. Blanco, and F. Sánchez-Alonso
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundExtensive evidence has confirmed no increased risk of cancer associated to either conventional synthetic DMARDs or anti-TNF in patients with rheumatic diseases. The risk of cancer in biologic (bDMARDs) different to anti-TNF and targeted synthetic (tsDMARDs) is considerably less investigated. As new therapies are emerging, more data in real-world registries are needed to confirm safety in other treatment groups.ObjectivesTo compare the risk of cancer of tsDMARDs and other bDMARDs versus anti-TNF in patients with rheumatic diseases.MethodsData of patients enrolled in BIOBADASER 3.0 up to October 2021 with the start of any bDMARD or tsDMARD were analyzed. For each group, demographic and clinical variables were estimated. Changes to therapy and occurrence of serious adverse events collected annually. Incident cancer was defined as any cancer during the exposure classified according to Meddra dictionary leading to therapy discontinuation. Incidence rate ratios of cancer per 1000 patients-year (PYs) and 95% confidence interval were estimated. Incidence rate ratio was calculated for each group versus anti-TNF.ResultsWe identified 271 cancers in BIOBADASER 3.0, corresponding to a cancer incident rate of 7.4 (6.5-8.3) per 1000 PY of exposure. Patients exposed to anti-TNF and anti-IL17 were younger, with lower disease duration and comorbidity versus other groups. Proportionally more malignancies were identified in the anti-CTLA-4 group (3.4%) versus the anti-TNF group (2.9%). The rates of incident cancer ranged between 2.6 events/1000 PY in the anti-IL17 group and 15.3 events/1000 PY in the anti-CTLA-4 group. The rate of cancer did not differ significantly in patients exposed to JAKi [0.8 (95% CI 0.4-1.5)], anti CD20 [1.1 (95% CI 0.6-1.8)], or anti-IL6 [1.3 (95% CI 0.9-1.9)] versus anti-TNF; it was significantly lower in patients exposed to anti-Il17 [0.4 (95% CI 0.2-0.9)], and significantly higher in patients exposed to anti-CTLA-4 [2.2 (95% CI 1.4-3.2)]. The most frequent malignancy was non-melanoma skin cancer, followed by solid cancer (mainly breast cancer with 24 events and lung cancer with 14 events) and melanoma (13 events).Table 1.New Cancer Diagnosis Among Patients with anti-TNF versus other therapiesAnti-TNF (N=6356)JAKi (N=1079)Anti-CD20 (N=667)Anti-IL6 (N=1178)Anti-CTLA-4 (N=783)Anti-IL17 (N=1051)Female, n (%)3738 (58.8)868 (80.4)523 (78.4)947 (80.4)598 (76.4)492 (46.81)Mean age, (SD)54.8 (14.7)58.5 (12.4)60.9 (13.6)59.8 (15.1)64.0 (12.8)52.2 (11.6)Mean start age, (SD)49.1 (14.0)56.6 (12.3)57.9 (13.5)55.7 (15.2)59.7 (13.0)49.8 (22.2)Disease duration, median (IQR)6.2[2.2-13.0]10.4[4.7 -17.2]11.0[5.1-18.5]8.3[3.2-15.1]10.3[5.2-17.0]3.1[0.3-10.7]Charlton Index1.9 (1.3)2.4 (1.6)2.4 (1.7)2.4 (1.7)2.8 (1.9)1.8 (1.3)First line biologic, n (%)99 (53.2)2 (22.2)1 (7.1)6 (20.0)5 (18.5)2 (66.7)New cancer diagnosis, n (%)186 (2.9%)9 (0.8%)14 (2.1%)30 (2.5%)27 (3.4%)5 (0.5%)Median years of follow-up months4.2 [2.3-7.3]2.4 [1.4-3.2]1.0 [1.0-1.0]2.6 [1.3-6.6]4.4 [1.5-5.7]1.8 [1-5-2.2]Time of exposure, yrs26233.51652.71871.53196.71762.11921Cancer Incidence Rate (per 1000 PY) ancer Incide7.1 (6.1-8.2)5.4 (2.8-10.5)7.5 (4.4-12.6)9.4 (6.6-13.4)15.3 (10.5-22.3)2.6 (1.1-6.3) .6 (1.1-6.3).5.2 (4.4-6.1)6.3 (1.6-8.1)5.9 (3.3-10.6)7.5 (5-11.2)10.8 (6.9-16.9)1.6 (0.5-4.8) .6 (0.5-40.3 (0.2-0.6)0 (0-0)1.1 (0.3-4.3)0.3 (0-2.2)0.6 (0.1-4)0 (0-0) (0-0)1-4)3)9)) Rate (per1.6 (1.2-2.2)1.8 (0.6-5.6)0.5 (0.1-3.8)1.6 (0.7-3.8)4 (1.9-8.3)1 (0.3-4.2)Rate ratio (vs anti-TNF)NA0.8 (0.4-1.5)1.1 (0.6-1.8)1.3 (0.9-1.9)2.2 (1.4-3.2)0.4 (0.2-0.9)ConclusionIn this register-based study, rates of incident cancer did not differ between patients treated with anti-TNF and other bDMARDs or tsDMARDs, with the possible exception of a potential increased risk in patients treated with anti-CTLA-4.AcknowledgementsThank you to all patients, rheumatologists, and to the research personnel from the Spanish Foundation of Rheumatology who made this study possible.Disclosure of InterestsIsabel Castrejon: None declared, Juan Molina Collada: None declared, Carolina Perez-Garcia: None declared, Paloma Vela-Casasempere Speakers bureau: ROCHE, UCB, GSK, LILLY, Consultant of: PFIZER, BMS, LILLY, UCB, GSK, Abbvie, Fresenius Kabi, Grant/research support from: ROCHE, ABBVIE, PFIZER, BMS, LILLY, SANDOZ, AMGEN, Cesar Diaz-Torne: None declared, Cristina Bohórquez: None declared, J M Blanco: None declared, Fernando Sánchez-Alonso: None declared
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- 2022
4. OP0138 RISK OF CANCER AFTER BIOLOGIC AND TARGETED SYNTHETIC DMARDS INITIATION IN PATIENTS WITH RHEUMATIC DISEASES AND A HISTORY OF PRIOR MALIGNANCY: DATA FROM THE BIOBADASER REGISTRY
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J. Molina Collada, F. Sánchez-Alonso, C. Bohórquez, C. Diaz-Torne, C. Perez-Garcia, J. M. Blanco, P. Vela-Casasempere, and I. Castrejon
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Rheumatology ,Immunology ,Immunology and Allergy ,General Biochemistry, Genetics and Molecular Biology - Abstract
BackgroundPatients with a history of cancer are routinely excluded from randomized controlled trials. As consequence, data on the safety of biologic disease modifying antirheumatic drugs (bDMARDS) and targeted synthetic (ts) DMARDs are limited. Although real world data from various national registries have not provided evidence of increased cancer recurrence, additional data from real-world registries may help to confirm safety of non-TNFi bDMARDs and tsDMARDs regarding cancer recurrence to guide treatment decisions.ObjectivesTo compare the risk of incident malignancy with exposure to different bDMARDs and tsDMARDs in patients with rheumatic diseases and a prior malignancy.MethodsThe study population comprised patients with a prior malignancy from the BIOBADASER 3.0 up to 2021. BIOBADASER is a large national drug safety registry of patients with rheumatic diseases starting treatment with any bDMARD or tsDMARD and followed thereafter at the time an adverse event or a change in biological therapy occurs. Incident cancer was defined as any cancer (new primaries, local recurrence or metastases) during the exposure classified according to Meddra dictionary. Incidence rate ratios of cancer per 1000 patients-year (PY) and 95% CI were estimated. Rates of incident cancer in tsDMARDs and other bDMARDs versus anti-TNF treated patients were compared.ResultsA total of 9,129 patients treated with bDMARDs and tsDMARDs are included in BIOBADASER 3.0 at the time of the study. Of them, 352 with a prior history of malignancy at time of enrollment were selected for analysis (Figure 1). Overall, there were 32 incident malignancies (17 solid cancer, 14 non-melanoma skin cancer and 1 melanoma). The overall rate of incident malignancy was 27.1 (95% CI 18.6-38.3) events/1,000 PY, ranging between none events/1000 PY in the anti-IL17 group to 51.7 events/1000 PY in the anti-CTLA-4 group (Table 1). The overall rate of incident cancer did not differ significantly in patients exposed to JAKi [0.6 (95% CI 0.1-2.5)], anti-CD20 [0.3 (95% CI 0.1-1.4)], anti-IL6 [1.2 (95% CI 0.5-3.4)] or anti-CTLA-4 [1.3 (95% CI 0.5-3.6) versus anti-TNF therapy. The rate of different types of cancer (melanoma, non-melanoma skin cancer or solid tumors) did not differ between the different treatment groups when compared to anti-TNF therapy (Table 1).Table 1.Baseline characteristics and rate of incident cancer.Anti-TNF(n = 185)JAKi(n = 61)Anti-CD20(n= 61)Anti-IL6(n= 68)Anti-CTLA-4(n= 47)Anti-IL17(n= 39)Total(n=352)Female, n (%)129 (69.7)49 (80.3)43 (70.5)54 (79.4)34 (72.3)21 (53.9)247 (70.2)Age, mean (SD)64.4 (13.1)66.7 (13.1)67.8 (10.0)70.5 (11.6)71.8 (10.4)59.5 (14.6)65.3 (13.0)Start treatment age, mean (SD)60.0 (12.9)64.8 (12.8)65.7 (9.6)67.3 (11.3)62.8 (12.7)56.9 (14.5)61.6 (12.8)Disease duration, median (IQR)6.7 (3.0-13.1)12.3 (7.4-19.6)10.8 (6.3-19.4)8.5 (4.0-16.8)8.2 (4.1-16.6)8.4 (4.7-16.1)7.0 (2.9-15.5)Time of follow-up months, mean (SD)23.1 (25.3)15.9 (13.3)11.5 (2.5)16.8 (17.6)23.7 (22.6)18.4 (15.5)17.5 (18.2)Charlson comorbidity index4.9 (2.0)5.2 (2.2)5.1 (2.0)5.5 (2.1)6.1 (2.6)6.9 (2.6)5.2 (2.1)Prior malignancyNon-lymphoproliferative (solid or melanoma), n (%)174 (94.5)58 (95.1)54 (88.5)65 (95.6)46 (97.9)36 (92.3)331 (94.0)Lymphoproliferative, n (%)9 (4.9)3 (4.9)13 (21.3)4 (5.9)4 (8.5)5 (12.8)29 (8.2)Metastatic cancer, n (%)2 (1.1)2 (3.3)2 (3.3)1 (1.5)3 (6.4)0 (0.0)7 (2.0)Incident cancerNew cancer diagnosis, n (%)182255032Time of exposure, sum (years)470,191,6163104,996,863,81178,6Rate of incident cancer (per 1,000 PY)38.3 (24.1-60.8)21.8 (5.5-87.3)12.3 (3.1-49.1)47.7 (19.8-114.5)51.7 (21.5-124.1)0 (0-0)27.1 (18.6-38.3)Rate ratio of incident cancer (vs anti-TNF)-0.6 (0.1-2.5)0.3 (0.1-1.4)1.2 (0.5-3.4)1.3 (0.5-3.6)--Figure 1.Flowchart of patients included.ConclusionThe risk of incident cancer in patients with rheumatic diseases and a prior malignancy does not differ according to the type of bDMARD and tsDMARD exposure.Disclosure of InterestsNone declared
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- 2022
5. AB0751 SAFETY AND PERSISTENCE OF USTEKINUMAB IN PATIENTS WITH PSORIATIC ARTHRITIS IN BIOBADASER
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P. Vela-Casasempere, Cristina Bohórquez, C. Diaz Torne, M. Freire-Gonzalez, Carlos Sánchez-Piedra, B. Magallon, R. Martin Domenech, J. del Pino Montes, Fernando Sánchez-Alonso, M. Pascual, N. Busquets-Pérez, F. J. Manero, and Lorena Expósito
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medicine.medical_specialty ,business.industry ,Immunology ,Arthritis ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Discontinuation ,Psoriatic arthritis ,Rheumatology ,Prednisone ,Internal medicine ,Psoriasis ,Cohort ,Ustekinumab ,Immunology and Allergy ,Medicine ,business ,Adverse effect ,medicine.drug - Abstract
Background:Ustekinumab has been efficacy and safety for psoriatic artritis in clinical trials.Objectives:To assess effectiveness, by means of drug persistence analisys, and safety of ustekinumab in patients with psoriastic arthritis in Biobadaser.Methods:BIOBADASER is the Spanish registry of biological drugs of the Spanish Society of Rheumatology and the Spanish Medicines Agency. We identified patients aged 18 years or more with psoriatic arthritis on Ustekinumab. A descriptive analysis was performed.The persistence of ustekinumab therapy was calculated with a Kaplan-Meier curve and was compared with the persistence of anti-TNF, according to line treatment. Log Rank test was used to establish a comparison. Adverse events occurring with ustekinumab are described according to year treatment.Results:One hundred and twelve patients were on ustekinumab. Most of them were on their second or third line treatment: 53.57% more than one biological therapy (BT), 19.64% second BT, 26.79% were naïve for BT. Most of them were on 45 mg dose: 88.24%. Median duration of disease at Ustekinumab initiation was 10.1 SD 7.2 years; 69.23% had peripheral arthritis; 45.24% had obesity and 39.29% were overweight; 40,6% were on prednisone and 59.82% on DMARD. The cause of discontinuation of treatment was mainly inefficacy (82.61%) and less common an adverse event (6.52%). The probability of persistence of treatment with ustekinumab was 0.83 (95% CI 0.63-0.92) at year 1, 0.79 (0.58-0.90) at year 2 and 0.79 (0.58-0.9) at year 3 when ustekinumab was prescribed as the first line treatment. The persistence decrease when ustekinumab was prescribe as a second and third treatment: being 0.53 (0.27-0.73) the first year, 0.46 (0.22-0.67) the second year and 0.46 (0.22-0.67) as a second line treatment and 0.58 (0.44-0.70) the first year, 0.33 (0.17-0.50) the second year and 0.33 (0.17-0.50) the third year as a third line treatment.The persistence was similar to anti-TNF treatment, according to line treatment. Adverse events were mainly mild (97.83%) and occurred the first year of treatment. Most of the adverse events were classified as “infections and infestations” (36.96%).Conclusion:The persistence of ustekinumab was high, being 83% at the end of the first year on treatment and 79% the second and the third year of treatment. The persistence of ustekinumab was higher when if it was the first line treatment compared as if it was used as the second o third BT option. The persistence of Ustekinumab is similar to the persistence of anti-TNF treatments in all the analyzed treatment lines (no statistically differences were found). Adverse events occurred mainly during the first year treatment. They were mainly mild adverse events and the frequency decreased within the second and third year of treatment.References:[1]Treatment with ustekinumab in a Spanish cohort of patients with psoriasis and psoriatic arthritis in daily clinical practice.Almirall M, Rodriguez J, Mateo L, Carrascosa JM, Notario J, Gallardo F. Clin Rheumatol. 2017 Feb;36(2):439-443;[2]Minimal disease activity in patients with psoriatic arthritis treated with ustekinumab: results from a 24-week real-world study.Napolitano M, Costa L, Caso F, Megna M, Scarpa R, Balato N, Ayala F, Balato A. J Clin Rheumatol. 2018 Oct;24(7):381-384;[3]Minimal Disease Activity and Patient-Acceptable Symptom State in Psoriatic Arthritis: A Real-World Evidence Study With Ustekinumab.Queiro R, Brandy A, Rosado MC, Lorenzo A, Coto P, Carriles C, Alperi M, Ballina J. Actas Dermosifiliogr. 2018 Jun 28;[4]An analysis of Drug Survival, Effectiveness, and Safety in Moderate to Severe Psoriasis Treated With Ustekinumab: An Observational Study of 69 Patients in Routine Clinical Practice.Salgüero Fernández I, Gil MH, Sanz MS, Gullón GR;Disclosure of Interests:None declared
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- 2020
6. AB1356-HPR GOUT IN SPANISH PRIMARY HEALHCARE CENTERS: STILL A LONG WAY TO GO
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Maria Antonia Pou, A. García-Guillén, S. Jeria, H. Corominas, C. Diaz Torne, S. Ferrer, and Alejandro Prada-Ojeda
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medicine.medical_specialty ,Joint deformity ,business.industry ,Immunology ,Adult population ,Primary health care ,Primary care ,Disease ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Gout ,Family medicine ,Internal medicine ,medicine ,Immunology and Allergy ,Proper treatment ,business - Abstract
Background:Gout has a prevalence >2.5% in the Spanish adult population. It is a chronic disease that without proper treatment causes pain, joint deformity and increased cardiovascular risk and mortality. Recent advances have demonstrated that if correctly treated the disease can be controlled and even ‘cured’. Most gouty patients are diagnosed and treated by general practitioners (GPs). There is evidence that the management if these patients is not good neither at Rheumatology Units nor at Primary Healthcare (PHC) centers.Several causes of this mismanagement can be found in the literature.Objectives:Design and evaluation of the results of a questionnaire created from a bibliographic search focused on areas of improvement of gout management in PHC.Methods:A search was made in Pubmed to identify the main barriers described in the management of patients with gout in primary care. The terms used were: “Gout”, “primary healthcare” and “education”. A Google Form of gout knowledge and management questionnaire was designed, taking into account what is described in the literature. The Google Form was sent to all GP from an urban area via mail and to other contacts via WhatsApp and twitter.Results:Responses were obtained from 224 GPs; 69.5% were women; 73.1% had between 11 and 30 years of professional experience; 96.4% answered that gouty are mostly controlled in primary care; 99.6% performs the diagnosis of gout without analysis of synovial fluid and 17% diagnosed only by clinics without urate levels; 55.9% of GPs do not use any reference guide. Of those who use, the 73% use GUIPCLINGOT and 40% use SEMGs one; 80.5% have not done any gout course in the last 5 years; 26% did not have access to a rheumatologist to confirm the gout diagnosis; only 30.8% knew the therapeutic objective of the urate lowering therapy (ULT); 28.6% considered the beginning of ULT after the first attack; 62% believed that the most important part of the treatment was changing diet and lifestyles; 88.8% did not perform any specific education for these patients by the nurse; just 37.2% carried out a treat-to-target strategy to lower urate levels.Conclusion:The questionnaire identifies multiple points of improvement for the management of this pathology in accordance with the described in the literature. Most GPs are unaware of the therapeutic objective of the ULT.Disclosure of Interests:None declared
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- 2020
7. THU0016 EPIGENOMIC ANALYSIS OF RA PATIENTS SHOWS DISTINCT BIOLOGICAL PROCESSES ASSOCIATED WITH ANTI-TNF RESPONSE
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M. Alperi-López, S. Sánchez Fernandez, Jordi Monfort, J. Tornero Molina, A. Erra, Jordi Lladós, S. Marsal, F.J. Blanco, Raimon Sanmartí, C. Marras Fernandez Cid, R. Garcia de Vicuna, Núria Palau, Isidoro González-Álvaro, A. Gomez, A. Fernández Nebro, Antonio Julià, C. Diaz Torne, and R. M. Lastra
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medicine.medical_specialty ,Treatment response ,business.industry ,Immunology ,EPIC ,General Biochemistry, Genetics and Molecular Biology ,Disease activity ,Disease evolution ,Rheumatology ,Internal medicine ,Lack of efficacy ,Immunology and Allergy ,Differential Methylation ,Medicine ,Interleukin production ,business ,Epigenomics - Abstract
Background:Blocking Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for approximately 60% of patients with rheumatoid arthritis (RA). To date, however, the biological basis of the lack of efficacy of anti-TNF agents is unknown.Objectives:The objective of present study was to characterize the biological basis of anti-TNF lack of efficacy in RA using an epigenomic data approach in two steps: first, to assess the differential methylation changes between responders and non-responders and second, to use this differential methylation profile in a systems biology approach to infer differential methylated biological modules according to anti-TNF response.Methods:A total of n=68 patients diagnosed with RA according to the ACR-EULAR criteria belonging to 16 Hospitals across Spain were recruited. All patients were >18 years old, with more than 6 months of disease evolution and a baseline disease activity of DAS28 > 3.2. Treatment response was defined according to the EULAR criteria at week 12. Good and moderate responders were aggregated into a single responder group. Genomic DNA was collected at baseline and the methylation profile was assessed using the Illumina Infinium EPIC array, which interrogates 850,000 methylation CpG sites across the genome. Differential Methylation analysis, biological pathway association and the systems Biology approach using Protein-Protein Interaction Networks, were conducted using the R statistical language and the Bioconductor libraries.Results:From 68 anti-TNF treated patients, n=27 (39.7%) were good responders, n=26 (38.2%) moderate responders and n=15 (22.05%) non-responders at week 12 of treatment. Differential methylation analysis identified two distinctive biological profiles associated with the clinical response: responders were associated to interleukin and cytokine production, and non-responders were associated with biological pathways associated to TGF-Beta production and T cell regulation. Using these differentially methylated profiles, epigenetic modules with differentially methylated hotspots between responders and non-responders were also found. Two epigenetic modules with significant enrichment in inflammatory and interleukin production and immune regulatory processes were validated in an independent patient cohort.Conclusion:The epigenetic analysis of whole blood from RA patients using a module-based approach shows reproducible biological mechanisms associated with the response to anti-TNF therapy.Acknowledgments:We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Antonio Gómez: None declared, Antonio Fernández Nebro: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research & Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer, Alba Erra: None declared, Simon Sánchez Fernandez: None declared, Jordi Monfort: None declared, Mercedes Alperi-López: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Rosario Garcia de Vicuna Grant/research support from: BMS, Lilly, MSD, Novartis, Roche, Consultant of: Abbvie, Biogen, BMS, Celltrion, Gebro, Lilly, Mylan, Pfizer, Sandoz, Sanofi, Paid instructor for: Lilly, Speakers bureau: BMS, Lilly, Pfizer, Sandoz, Sanofi, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Cesar Diaz Torne: None declared, Carlos Marras Fernandez Cid: None declared, Jesús Tornero Molina: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Sara Marsal: None declared
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- 2020
8. SAT0006 SIMULTANEOUS ANALYSIS OF ANTI-CCP, RHEUMATOID FACTOR, ANTI-PAD4 AND ANTI-CARBAMYLATED PROTEIN ANTIBODIES REVEALS INTERACTION EFFECTS WITH RESPONSE TO ANTI-TNF THERAPY IN RHEUMATOID ARTHRITIS
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M. Lopez Lasanta, A. Erra, S. Marsal, M. Alperi-López, Isabel Haro, M. L. García Vivar, Raimon Sanmartí, F.J. Blanco, S. Sánchez Fernandez, Núria Palau, Isidoro González-Álvaro, Jordi Monfort, R. Castellanos, Antonio Julià, A. Gomez, C. Diaz Torne, Antonio Fernández-Nebro, R. M. Lastra, Jordi Lladós, and Antonio Juan Mas
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medicine.medical_specialty ,biology ,business.industry ,Immunology ,Positive interaction ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Internal medicine ,Rheumatoid arthritis ,medicine ,Clinical endpoint ,Drug response ,biology.protein ,Immunology and Allergy ,Rheumatoid factor ,Anti-TNF therapy ,Antibody ,business ,Prospective cohort study - Abstract
Background:Blocking of the Tumor Necrosis Factor (TNF) activity is a successful therapeutic approach for 2 out of 3 Rheumatoid Arthritis patients. Identifying the patients that will not respond to this therapeutic approach is a major translational goal in RA. Association of seropositivity to rheumatoid factor (RF) or anti-cyclic-citrullinated antibodies (anti-CCP) with anti-TNF response has proven inconclusive, suggesting that other yet unexplored biomarkers could be more informative for this goal.Objectives:We tested the association of two recently introduced biomarkers in RA: anti-carbamylated protein antibodies (anti-CarP) and anti-peptidylarginine deiminase type 4 (anti-PAD4).Methods:A prospective cohort of n=80 RA patients starting anti-TNF therapy was recruited and levels for all four autoantibodies -RF, anti-CCP, anti-CarP and anti-PAD4- were measured at baseline. The change in DAS28 score between baseline and week 12 of therapy was used as the clinical endpoint.Results:Single marker-analysis showed no significant association with drug response. However, when testing for interactions between autoantibodies, we found highly significant associations with drug response. Anti-CCP and RF showed a positive interaction with the response to anti-TNF therapy (P=0.00068), and anti-PAD4 and antiCarP titers showed a negative interaction with the clinical response at week 12 (P=0.0062). Using an independent retrospective sample (n=199 patients), we validated the interaction between anti-CCP and RF with the clinical response to anti-TNF agents. (P=0.044).Conclusion:The results of this study show that interactions between antibodies are important in the response to anti-TNF therapy and suggest potential pathogenic relationships.Acknowledgments :We would like to thank the clinical researchers and patients participating in the IMID Consortium for their collaborationDisclosure of Interests:Antonio Julià: None declared, Maria Lopez Lasanta: None declared, Francisco Blanco: None declared, Antonio Gómez: None declared, Isabel Haro: None declared, Antonio Juan Mas: None declared, Alba Erra: None declared, Mª Luz García Vivar: None declared, Jordi Monfort: None declared, Simon Sánchez Fernandez: None declared, Isidoro González-Álvaro Grant/research support from: Roche Laboratories, Consultant of: Lilly, Sanofi, Paid instructor for: Lilly, Speakers bureau: Abbvie, MSD, Roche, Lilly, Mercedes Alperi-López: None declared, Raúl Castellanos: None declared, Antonio Fernandez-Nebro: None declared, Cesar Diaz Torne: None declared, Núria Palau: None declared, Raquel M Lastra: None declared, Jordi Lladós: None declared, Raimon Sanmarti: None declared, Sara Marsal: None declared
- Published
- 2020
9. A modified Delphi exercise to determine the extent of consensus with OMERACT outcome domains for studies of acute and chronic gout
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W J, Taylor, H R, Schumacher, H S B, Baraf, P, Chapman, L, Stamp, M, Doherty, F, McQueen, N, Dalbeth, N, Schlesinger, D E, Furst, J, Vazquez-Mellado, J Vazquez, Mellado, M A, Becker, A, Kavanaugh, W, Louthrenoo, T, Bardin, D, Khanna, L S, Simon, H, Yamanaka, H K, Choi, X, Zeng, V, Strand, R, Grainger, D, Clegg, J A, Singh, C, Diaz-Torne, M, Boers, P, Gow, V G, Barskova, Epidemiology and Data Science, and CCA - Disease profiling
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Consensus ,Delphi Technique ,Gout ,Immunology ,MEDLINE ,Physical exercise ,General Biochemistry, Genetics and Molecular Biology ,Quality of life ,Rheumatology ,Internal medicine ,medicine ,Immunology and Allergy ,Health Status Indicators ,Humans ,Hyperuricemia ,Response rate (survey) ,business.industry ,Tophus ,medicine.disease ,Treatment Outcome ,Acute Disease ,Chronic Disease ,Physical therapy ,business - Abstract
Objectives: To reach consensus with recommendations made by an OMERACT Special Interest Group (SIG). Methods: Rheumatologists and industry representatives interested in gout rated and clarified, in three iterations, the importance of domains proposed by the OMERACT SIG for use in acute and chronic gout intervention studies. Consensus was defined as a value of less than 1 of the UCLA/RAND disagreement index. Results: There were 33 respondents (61% response rate); all agreed the initial items were necessary, except “total body urate pool”. Additional domains were suggested and clarification sought for defining “joint inflammation” and “musculoskeletal function”. Items that demonstrated no clear decision were re-rated in the final iteration. There were six highly rated items (rating 1–2) with four slightly lower rating items (rating 3) for acute gout; and 11 highly rated items with eight slightly lower ratings for chronic gout. Conclusions: Consensus is that the following domains be considered mandatory for acute gout studies: pain, joint swelling, joint tenderness, patient global, physician global, functional disability; and for chronic gout studies: serum urate, gout flares, tophus regression, health-related quality of life, functional disability, pain, patient global, physician global, work disability and joint inflammation. Several additional domains were considered discretionary.
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- 2007
10. AB0688 Anti-C1Q antibody as a biomarker for systemic lupus erythematosus
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J.M. de Llobet, Ivan Castellví, M.E. Cόrica, C. Diaz Lopez, Ana Laiz, P. Moya Alvarado, Miguel Sarmiento, G. Lopez Sanchez, C. Geli, and C. Diaz Torne
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medicine.medical_specialty ,Systemic disease ,Systemic lupus erythematosus ,business.industry ,Immunology ,Autoantibody ,Lupus nephritis ,Complement deficiency ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Nephropathy ,immune system diseases ,Internal medicine ,Immunology and Allergy ,Medicine ,Biomarker (medicine) ,skin and connective tissue diseases ,business - Abstract
Background SLE is the prototype of the autoimmune systemic disease. It is characterized by the production of autoantibodies against the cell nucleus components in association with multiple clinical manifestations that affect different organs 1 . There are studies that support the hypothesis that the components of the classic pathway of the complement are necessary to produce the phagocytic clearance of the apoptotic cells, which provides a possible explanation for the high frequency of SLE among patients with deficiencies of said components, especially C1q 2 . Approximately one third of the patients with SLE have high serum levels of anti-C1q antibodies 3 . Objectives To observe the value of anti-C1q antibody as a biomarker in SLE. Methods The clinical charts of 135 patients with SLE being followed up by the Rheumatology Unit of Hospital de la Santa Creu i Sant Pau and who had been tested to determine the presence of anti-C1q antibody were analyzed retrospectively. We studied clinical, hematological and immunological variables. Results It was observed that patients with anti-C1q antibodies were younger at the time of disease onset (32.9 vs 44.8 years, p We found a statistically significant relation between the presence of anti-C1q antibodies and some of the most recognized biomarkers of SLE: anti- DNA ds ( p =0.034), anti- Sm( p =0.045), homogeneous ANA ( p =0.031) and low concentration of C3 complement ( p =0.006). As it was observed in previous studies, we found a higher frequency of lupus nephritis in anti-C1q positive patients but this difference was not statistically significant (38.9% vs 27.3%, p=0139). We observed that 8 out of 9 patients with vasculitis present anti-C1q antibodies establishing a statistically significant relation ( p Conclusions The anti-C1q antibodies have been associated with different clinical, hematological and immunological manifestations in patients with SLE, especially with lupus nephropathy, hypocomplementemia and leucopenia. Our results reflect partially what was published previously. We were able to observe that the anti-C1q positive patients present, in a statistically significant way, more positivity for anti-DNA ds , anti-Sm y homogeneous ANA antibodies. With normal values of this biomarkers, the flares of SLE are rare. This could indicate that the presence of anti-C1q antibody is a factor of bad prognosis, both renal and globally. As it is confirmed in recent studies, the value of anti-C1q as a biomarker in lupus nephropathy should be taken with caution. However, its presence together with other biomarkers of SLE, could be helpful for the diagnosis References Firestein GS, Budd RC, Harris Jr. ED, McInnes IB, Ruddy S, Sergent JS. Kelly’s Textbook of Rheumatology; 2009, 8° ediciόn, Editorial Saunders Elsevier Crow MK. Developments in the clinical understanding of lupus. Arthritis Res Ther. 2009;11(5):245-56. Pickering MC, Botto M, Taylor PR, Lachmann PJ, Walport MJ. Systemic lupus erythematosus, complement deficiency, and apoptosis. Adv Immunol. 2000;76:227-324 Disclosure of Interest None Declared
- Published
- 2013
11. SAT0125 Association of Rituximab Levels to Clinical Response and B Cell Recovery in Rheumatoid Arthritis Patients
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C. Geli, J.M. de Llobet, M. P. Sarmiento Guevara, M. A. Ortiz, Nilka Lineth Torres, Silvia Vidal, Cándido Juárez, D. Nagore, C. Diaz Lopez, and C. Diaz Torne
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biology ,business.industry ,Immunology ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Peripheral blood ,Disease course ,medicine.anatomical_structure ,Rheumatology ,immune system diseases ,hemic and lymphatic diseases ,Rheumatoid arthritis ,medicine ,biology.protein ,Immunology and Allergy ,Rituximab ,Antibody ,business ,B cell ,medicine.drug - Abstract
Background Rituximab effects in rheumatoid arthritis patients have been extensively described in the literature. However, kinetics of rituximab levels in serum and their association with the clinical and immunological changes in these patients remain unknown. Methods Thirty five patients were treated with three courses of rituximab (one course: 1000 mg administered intravenously on days 1 and 15). Levels of rituximab in the serum were determined by ELISA (Promonitor ®-RTX) before initiating each treatment course (t=0d) and at 30, 90 and 180 days. We then analyzed the association of serum rituximab levels with changes in DAS28, PCR, ESR, IgG, IgM and IgA levels, B cell frequency, RF and C3 and C4 complement. Results The peak of rituximab levels was observed at 30 days after initiating each course. Rituximab levels ranged from 13000 to115000 ng/ml at 30d. At 90d levels decreased significantly, but they were still detectable in 80% of patients. Those patients with higher levels in the first course of the treatment presented also higher levels in the second and third courses. No anti-rituximab antibodies were detected during follow-up. To analyze the association of rituximab levels with clinical and immunological parameters, patients were segregated in two groups according to 30d-rituximab levels: group H ( >56000 pg/ml) (52% of patients) and group L ( Conclusions Lower levels of rituximab in serum were associated with a better clinical response and later B cell recovery. Circulating levels of rituximab may be conditioned by the relocation of rituximab to the extravascular compartment. In this extravascular compartment, rituximab could thus expand its mechanism of action beyond the peripheral blood. Disclosure of Interest None Declared
- Published
- 2013
12. SAT0151 Pet/Ct Scan in Polymyalgia Rheumatica: A Prospective Study of 26 Patients
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A. Fernandez Leon, A. Laiz Alonso, A. Rodriguez de la Serna, I. Castellvi Barranco, M.E. Corica, M. P. Sarmiento Guevara, P. Moya Alvarado, C. Geli Ferrer, E. Toniolo, J. M. Llobet Zubiaga, and C. Diaz Torne
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musculoskeletal diseases ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,education ,Immunology ,Physical examination ,medicine.disease ,Spinal column ,General Biochemistry, Genetics and Molecular Biology ,Rheumatology ,Surgery ,Polymyalgia rheumatica ,Jaw claudication ,Internal medicine ,medicine ,Immunology and Allergy ,Medical history ,Arteritis ,skin and connective tissue diseases ,business ,Rheumatism - Abstract
Background Polymyalgia rheumatica (PMR) may be associated with arteritis of the aorta and its major branches including temporal artery. The delay in the diagnosis of GCA and therefore, in its treatment can have serious consequences. Objectives The primary objective of this study is to evaluate by PET / CT scan the incidence of GCA in patients with PMR and the existence of underlying malignancies since, so far, no clear association has been established between them, which is a common clinical concern. The secondary objective is to study the joint involvement in PMR. Methods We studied prospectively all patients with clinical suspicion of PMR referred to the Rheumatology Unit, the Emergency Department and the Internal Medicine and Rheumatology day hospitals from January 2010 to November 2012. All patients who met the PMR EULAR / ACR 2012 classification criteria1 underwent medical history and physical examination, complete blood tests (including TSH, tumor markers and blood and urine cultures), and chest x-rays. We completed the diagnosis of the remaining patients after other pathologies were excluded, with a PET/CT scan. Results We studied a total of 26 patients, 15 women and 11 men, with a mean age of 75.9 years. Of these patients, 2 had aortic uptake confirming the diagnosis of GCA. Asthenia was observed in 79% of the patients with PMR and in all patients with GCA. 41% of the PMR patients and 50% of the ACG patients suffered weight loss. All patients had shoulder and/or hip pain. Peripheral arthritis was observed only in the PMR group (15.34%). As for the specific symptoms of GCA, 3 PMR patients and 1 with GCA patient had headaches. Only 1 patient with a final diagnosis of GCA referred amaurosis fugax and none had jaw claudication. We observed similar values of mean ESR (71.8 mm / hour in PMR and 62.5mm/hour in GCA) and mean CRP (55.4 mg/l in PMR and 43.9 mg / l in ACG). Rheumatoid factor and anti-CCP antibodies were negative in all cases. Regarding the results of the PET, besides the two vasculitis, we also diagnosed 1 patient with lymphoma and 1 with colon adenoma with high grade dysplasia (both later confirmed by biopsy). Girdles uptake was observed in 84.6% (n = 22)of the patients, 76.9% (n = 20) in the scapular and 61.5% (n = 16)in the pelvic girdle. There was uptake in the spinal column in 31.6% (n = 9) of the patients and 11% (n = 4) of the patients had uptake in peripheral joints. All patients diagnosed from neoplasia or vasculitis presented uptake in at list one girdle. Conclusions The PET modified the diagnosis in 4 patients (15.38%), confirming the presence of a disease significant enough to suggest the performance of this study in the diagnostic algorithm of the disease. A larger sample is needed to confirm our initial results. The PET helped diagnose joint involvement in over 80% of the cases. We observed no clinical or laboratory features that may help in the differential diagnosis of patients. References Dasgupta B, Cimmino MA, Kremers HM, et al. 2012 Provisional classification criteria for polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Arthritis Rheum 2012;64:943-54. Disclosure of Interest None Declared
- Published
- 2013
13. FRI0224 Predictive factors of response to tocilizumab in patients with active rheumatoid arthritis
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A. Rodriguez de la Serna, Raimon Sanmartí, Javier Narváez, Nolla Jm, Berta Magallares, Delia Reina, JM Llobet, Silvia Garcia-Diaz, Hèctor Corominas, C. Diaz Torne, and Maria Victoria Hernández
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musculoskeletal diseases ,medicine.medical_specialty ,Multivariate analysis ,business.industry ,Immunology ,Disease ,Logistic regression ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Therapeutic goal ,Surgery ,chemistry.chemical_compound ,Tocilizumab ,Rheumatology ,chemistry ,Internal medicine ,Rheumatoid arthritis ,medicine ,Immunology and Allergy ,Observational study ,In patient ,skin and connective tissue diseases ,business - Abstract
Objectives To evaluatethe efficacy and identify predictors of response to tocilizumab (TCZ) in patients with rheumatoid arthritis. Methods A multi-center ambispective observational study in 126 patients with active rheumatoid arthritis treated with TCZ. The variables associated to achieve the therapeutic goal (remission of the disease defined as a DAS28 30 mm / h (OR=19.07, 95% CI: 2.7, 133.7) and the presence of extra-articular manifestations of the disease (OR = 15.5, 95% CI 2.3, 102.3). Factors that decreased it were hemoglobin (OR = 0.53, 95% CI: 0.32, 0.91), the baseline DAS28-ESR (OR = 0.30, 95% CI: 0.15, 0.64) and the number of previous DMARDs used (OR = 0.42, 95% CI: 0.22, 0.78). The only significant factor that reduced the possibility of DAS28-ESR response
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- 2013
14. 'Gout was like the boss'. A qualitative study exploring the impact of gout on employment.
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Diaz-Torne C, Pou MA, Horne A, Gasteiger C, and Dalbeth N
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- Humans, Male, Middle Aged, Female, Adult, New Zealand epidemiology, Spain epidemiology, Aged, Quality of Life, Interviews as Topic, Workplace psychology, Gout psychology, Gout epidemiology, Qualitative Research, Employment
- Abstract
Objective: Previous research has identified that gout impacts various domains of daily life. However, there have been no qualitative studies focusing on employment. This study aimed to understand the impact of gout on employment., Methods: Semistructured interviews were conducted in Spain and Aotearoa/New Zealand, in people with gout (according to the 2015 American College of Rheumatology/European Alliance of Associations for Rheumatology criteria) who had experienced a gout flare during their employment. The interviews were guided by questions exploring the impact on employment, job changes, disclosure and co-workers' reactions. Data were analysed thematically., Results: Eighteen participants were interviewed (89% male, mean age 52.9 years). Six themes were identified. The characteristics of the disease (pain intensity, tophi and joints affected) and the job itself (including physical job requirement and workplace flexibility) determined the experience of working with gout. The experiences were divided into physical (from total incapacity to working despite pain), emotional (feeling responsible, embarrassment, guilt and depression) and social (including disclosure responses and financial impact). Gout management strategies including rapid gout flare management and urate-lowering therapy reduced the number of flares and the intensity of pain, and allowed work attendance and participation., Conclusion: Both gout and work characteristics influence the employment experience for people with gout. Effective management of gout led to improved work experiences in all its domains., Competing Interests: Competing interests: CD-T has received speaker fees from AsacPharma. ND has received consulting fees, speaker fees or grants from AstraZeneca, Novartis, Horizon, Selecta, Arthrosi, JW Pharmaceutical Corporation, PK Med, LG Chem, JPI, PTC Therapeutics, Protalix, Unlocked Labs, Hikma, Dexcel Pharma outside the submitted work. MAP, AH and CG have nothing to disclosure., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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15. [Gout, beyond the joint: How should we treat it?]
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Pou MA, Martinez-Laguna D, and Diaz-Torne C
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- Humans, Uric Acid blood, Uric Acid metabolism, Spain, Patient Education as Topic, Life Style, Gout Suppressants therapeutic use, Prevalence, Diet, Risk Factors, Incidence, Medication Adherence, Cardiovascular Diseases prevention & control, Cardiovascular Diseases etiology, Cardiovascular Diseases therapy, Gout therapy, Gout diagnosis, Hyperuricemia therapy, Hyperuricemia diagnosis, Hyperuricemia etiology
- Abstract
Gout is a disease caused by the chronic deposition of monosodium urate crystals. Its clinical presentation as an acute, self-limiting arthritis and the belief that it is a banal, self-inflicted disease have led to its poor management. Despite advances in the knowledge of the disease and the simplicity of its management, no more than 30% of patients are well treated. In Spain, the prevalence of gout is 2.5% and its incidence is increasing. In the following article we will review the pathogenesis of gout and hyperuricaemia, highlighting the greater weight of genetics and renal function over diet. We will look at the consequences of crystal deposition. Gout, in addition to its joint presentation and renal involvement, has been shown to be an independent cardiovascular risk factor. Hypouricemic therapy is the most important treatment, as it is the one that dissolves the crystals and cures the disease. This requires the sustained achievement of uricemia levels below 6mg/dl. We will also review preventive and flares treatment, as well as the role of patient education in terms of both lifestyle and dietary habits and adherence to pharmacological treatment., (Copyright © 2023 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)
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- 2024
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16. Are There Sex-Related Differences in the Effectiveness of Janus Kinase Inhibitors in Rheumatoid Arthritis Patients?
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Martinez-Molina C, Feliu A, Park HS, Juanes A, Diaz-Torne C, Vidal S, and Corominas H
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Background : There is evidence suggesting the existence of sex differences in the effectiveness of specific drug classes for rheumatoid arthritis (RA). Our study stands as the first to elucidate sex-related differences in the effectiveness of Janus kinase (JAK) inhibitors. Methods : The study involved 150 RA patients treated with tofacitinib, baricitinib, upadacitinib, or filgotinib between September 2017 and October 2023. Sex differences in achieving remission and low disease activity (LDA) were identified through logistic regression analyses. Sex disparities in treatment effectiveness survival were evaluated through the Kaplan-Meier estimate, employing the log-rank test for comparison. The Cox model was applied to analyze the variable sex as a potential factor that could influence the maintenance of the JAK inhibitor treatment effectiveness. Results : Concerning the achievement of remission and LDA, no differences were observed between sexes in terms of the 28-joint Disease Activity Score (DAS28) C-reactive protein (CRP), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). With respect to the DAS28-erythrocyte sedimentation rate (ESR), female patients, compared to males, possessed 70% lower odds of achieving remission ( p = 0.018) and 66% lower odds of achieving LDA ( p = 0.023). No differences were observed in treatment effectiveness survival between sexes ( p = 0.703). Sex was not found to influence the survival of JAK inhibitor treatment effectiveness ( p = 0.704). Conclusions : Being a female or male patient does not entail differences in the effectiveness of the JAK inhibitor treatment. Our findings encourage the consideration of a global pool of composite indices (DAS28-ESR/CRP, CDAI, SDAI) to measure RA disease activity, thus individualizing the target value as advocated by the treat-to-target strategy.
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- 2024
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17. Application of the 2023 ACR/EULAR classification criteria for calcium pyrophosphate deposition disease in a seronegative rheumatoid arthritis cohort.
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Codes-Méndez H, Sainz L, Park HS, Corominas H, and Diaz-Torne C
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- Humans, Severity of Illness Index, Chondrocalcinosis diagnosis, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid epidemiology
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Competing Interests: Competing interests: None declared.
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- 2024
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18. Prognostic significance of lymphocytic foci composition in minor salivary gland biopsies for severe disease flare and severity in Sjögren's syndrome: a 3-year follow-up cohort study.
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Park HS, Martínez-Martínez L, Magallares López B, Castellví I, Moya P, Codes-Mendez H, Hernandez Sosa N, Diaz-Torne C, Laiz A, Sainz L, Tandaipan JL, Mariscal A, Franco-Leyva T, Casademont J, Juarez C, and Corominas H
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- Humans, Follow-Up Studies, Prognosis, Cohort Studies, Symptom Flare Up, B-Lymphocytes pathology, Biopsy, Inflammation pathology, Salivary Glands, Minor pathology, Sjogren's Syndrome, Guanidines
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Introduction: This was an ambispective cohort study evaluating the prognostic significance of lymphocytic foci and its lymphoid composition in minor salivary gland biopsy (MSGB) for short-term disease flare and severity in Sjögren's syndrome (SS)., Methods: The inclusion criteria comprised individuals meeting the ACR/EULAR 2016 criteria who underwent MSGB with an infiltration of more than 50 lymphocytes and received clinical diagnosis between September 2017 and December 2018. Patients with inadequate biopsy samples were excluded. The number of lymphocytic foci and their lymphoid composition in MSGB were assessed using immunofluorescence staining. Major organ damage and improvements in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) were measured. Statistical analyses, including Cox and linear regressions, were conducted., Results: A total of 78 patients with at least one lymphocytic focus were included in the study. The presence of higher T-cell counts in lymphocytic foci in MSGB was associated with severe disease flare, and a logarithmic transformation of T-cell count indicated increased risk (HR 1.96, 95% CI 0.91-4.21). Improvements in the ESSDAI were associated with higher total lymphocyte count and T- and B-cell numbers in the lymphoid composition of the lymphocytic foci. Seropositive patients exhibited higher T CD4+ cell numbers. Correlation analysis showed negative associations between age and lymphocytic foci and the T-cell count. Positive correlations were observed between antinuclear antibody (ANA) titers and total lymphocyte numbers., Discussion: Patients with a higher number of T cells in the lymphocytic infiltrates of lymphocytic foci may have a two-fold risk of severe disease flare. The number of B cells and T CD4+ cells in the lymphocytic infiltrates of lymphocytic foci showed a weak but positive relation with the ESSDAI improvement during follow-up. Age and seropositivity appeared to influence the lymphoid composition of the lymphocytic foci., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Park, Martínez-Martínez, Magallares López, Castellví, Moya, Codes-Mendez, Hernandez Sosa, Diaz-Torne, Laiz, Sainz, Tandaipan, Mariscal, Franco-Leyva, Casademont, Juarez and Corominas.)
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- 2024
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19. Tofacitinib and Baricitinib in Type 2 Diabetic Patients with Rheumatoid Arthritis.
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Martinez-Molina C, Diaz-Torne C, Park HS, Feliu A, Vidal S, and Corominas H
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- Humans, Glycated Hemoglobin, Retrospective Studies, Treatment Outcome, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid drug therapy, Azetidines, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Piperidines, Purines, Pyrazoles, Pyrimidines, Sulfonamides
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Background and Objectives : Recently, a randomized controlled trial suggested a potential benefit of baricitinib in patients with diabetes mellitus, preserving β-cell function. However, the clinical evidence currently available is limited. We aimed to assess the potential impact of tofacitinib and baricitinib on type 2 diabetes mellitus (T2DM) patients with rheumatoid arthritis. Materials and Methods : The candidates for this observational, retrospective, single-center study were selected from a cohort of 120 rheumatoid arthritis patients treated with tofacitinib or baricitinib between September 2017 and September 2023. The eligibility criteria included patients with T2DM who were receiving oral antidiabetic drugs (OADs). The primary outcome was the glycosylated hemoglobin (HbA1c) value after 6 months of a JAK inhibitor treatment. Secondary outcomes included body mass index (BMI) and rheumatoid arthritis disease activity. Differences were evaluated using Fisher's exact test, as well as the Mann-Whitney test or the Wilcoxon test. Results : Thirteen patients were included; 46.2% (6/13) underwent treatment with tofacitinib, while 53.8% (7/13) were treated with baricitinib. At 6 months, baricitinib treatment resulted in a reduction in HbA1c ( p = 0.035), with 57.1% (4/7) of patients achieving values <7%, and 28.6% (2/7) of patients requiring a reduction in OAD dosage. Concerning BMI, an increase ( p = 0.022) was observed at 6 months following baricitinib administration. All the patients treated with either tofacitinib or baricitinib achieved remission or low disease activity, without requiring statistically significant changes in concomitant rheumatoid arthritis treatment. Conclusions : In T2DM patients with rheumatoid arthritis, baricitinib can improve insulin sensitivity and glucose uptake, enabling the optimization of T2DM management., Competing Interests: The authors declare no conflicts of interest.
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- 2024
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20. Validation of gout diagnosis in electronic primary care medical records: A population-based study.
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Pou MA, Martinez-Laguna D, Estebanez JL, Aivar M, Gayarre R, Conesa A, Hoyo J, Carbonell C, Reyes C, and Diaz-Torne C
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- Humans, Cross-Sectional Studies, Electronic Health Records, Electronics, Gout Suppressants, Primary Health Care, Gout diagnosis, Gout drug therapy, Gout epidemiology, Uric Acid
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Objective: The main objective of the study was to see the concordance between the diagnosis of gout recorded in primary care electronic medical records and the ACR/EULAR 2015 classification criteria., Methods: A cross-sectional study was conducted using electronic medicals records in 7 primary care centres of Barcelona. Patients' data to study clinical diagnose and management was gathered from the primary care electronic medical records of the Catalonian health institute (Institut Català de la Salut, ICS) and phone interview. Patients were considered to have gout if they scored 8 or more points on the EULAR/ACR 2015 classification criteria for gout., Results: In total, 70.9% of the patients with a gout diagnosis met ACR/EULAR 2015 criteria. Adding a hyperuricemia in a blood test in the EMR increased the percentage to 78.9%. 29.8% of the gout patients were not receiving urate-lowering therapy. 62.3% of the treated patients did not achieve the target uricemia (< 6mg/dL)., Conclusions: The majority of gout patients from primary care electronic medical records fulfil ACR/EULAR gout criteria. This database can be used for observational studies. In most of the gout patients the urate target was not achieved., (Copyright © 2023 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)
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- 2023
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21. Outcome reporting in randomized trials in gout: A systematic scoping review from the OMERACT gout working group assessing the uptake of the core outcome set.
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Morillon MB, Nørup A, Singh JA, Dalbeth N, Taylor WJ, Kennedy MA, Pedersen BM, Grainger R, Tugwell P, Perez-Ruiz F, Diaz-Torne C, Edwards NL, Shea B, Ellingsen TJ, Christensen R, and Stamp LK
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- Humans, Randomized Controlled Trials as Topic, Systematic Reviews as Topic, Outcome Assessment, Health Care, Uric Acid, Gout drug therapy
- Abstract
Objective: The selection and reporting of core outcome measures in clinical trials is essential for patients, researchers, and healthcare providers for clinical research to have an impact on healthcare. In this systematic scoping review, we aimed to quantify the extent to which gout clinical trials are collecting and reporting data in accordance with the core outcome domains from Outcome Measures in Rheumatology (OMERACT) published in 2009 applicable for both acute and chronic trials and evaluate the reporting according to the core domains before and after the 2009 OMERACT endorsement., Methods: We searched multiple databases PubMed, EMBASE, the Cochrane Library including the Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews (CDSR) and www., Clinicaltrials: gov for randomized controlled trials (RCTs) allocating people with gout versus an active pharmacological gout treatment or a control comparator (no date limitation). We extracted the data in accordance with the core outcome sets, focusing individually on core outcome domains and the core outcome measurements for acute and chronic trials, respectively. In this study 'Acute trials' reflect studies that describe interventions for short term management of gout flares, and 'chronic trials' describe interventions for long-term urate lowering therapy in the management of gout., Results: From 8,522 records identified in the database search, 134 full text papers were reviewed, and 71 trials were included, of which 36 were acute and 35 were chronic. Only 3 of 36 (8%) acute trials reported all five core domains and none of the 35 included chronic trials reported all 7 core domains. In the acute trials, twenty-seven unique measurement instruments across the 5 core domains were identified. For chronic trials there were 31 unique measurement instruments used across the 7 core domains. Serum urate was reported in 100% of the chronic trials and gout flares in 80%. However, other core domains were reported in <30% of chronic trials. In particular the patient-important domains such as HR-QOL, patient global assessment and activity limitations were rarely reported. A broad variety of different measurement instruments were used to assess each endorsed core domain, a minority of trials used the OMERACT endorsed instruments. For acute trials, the number reporting on all core domains was consistently low and no change was detected before and after the endorsement of the core domains in 2009. None of the included chronic trials reported on all 7 endorsed core domains at any time., Conclusion: In this study we found a low adherence with the intended endorsed (i.e., core) outcome domains for acute and chronic gout studies which represents a poor uptake of the global OMERACT efforts for the minimum of what should be measured in clinical trials. In addition, there is a significant variation in how the OMERACT endorsed outcome domains have been measured. This systematic review demonstrates the need for continuous encouragement among gout researchers to adhere to OMERACT core domains as well as further guidance on outcome measurements reporting., Registration: Prospero: CRD42019151316., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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22. Effectiveness and safety of anakinra in gouty arthritis: A case series and review of the literature.
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Jeria-Navarro S, Gomez-Gomez A, Park HS, Calvo-Aranda E, Corominas H, Pou MA, and Diaz-Torne C
- Abstract
Background: Gout is the most common type of inflammatory arthritis. Nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine are the first-line agents, although they are contraindicated in many patients. Blockade of IL-1 with anakinra can be an alternative., Objective: To present a case series of 10 difficult-to-treat gout patients treated with anakinra and perform a scoping review of the effectiveness and safety of anakinra in gout patients., Methods: A total of 1,519 citations were screened. The reviewers ran a two-stage screening process by title/abstract and full-text reading. Thirty-eight articles finally met the selection criteria and were included for data extraction and synthesis. Experience in difficult-to treat and complex clinical scenarios, such as active infection, hemodialysis, and transplantation, were specifically described., Results: The study sample comprised 551 patients, from whom 648 flares were finally analyzed. The mean age was 57.9 years, and 82.9% were men. The clinical presentation was polyarticular in 47.5% and tophaceous in 66.9%. Sixty-five patients with an active infection, 41 transplanted patients and 14 in haemodyalisis treated with anakinra are described. More than half of the patients had >1 associated comorbidity. Anakinra was effective both for flares (94%) and for long-term treatment (91%) and well tolerated. In the case of flares, 34 (6.7%) adverse effects were registered. Adverse events were more prevalent in long-term treatment., Conclusion: Anakinra was effective and safe for management of gout flares in difficult-to-treat patients. It has been used in multiple complex scenarios, such as active infections, dialysis, transplantation, chronic kidney disease, and polyarticular gout. Anakinra has also proven effective as long-term treatment, although there are more concerns about its safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jeria-Navarro, Gomez-Gomez, Park, Calvo-Aranda, Corominas, Pou and Diaz-Torne.)
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- 2023
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23. Risk of Parkinson's disease in a gout Mediterranean population: A case-control study.
- Author
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Pou MA, Orfila F, Pagonabarraga J, Ferrer-Moret S, Corominas H, and Diaz-Torne C
- Subjects
- Male, Humans, Female, Aged, Adult, Case-Control Studies, Uric Acid, Retrospective Studies, Cohort Studies, Risk Factors, Parkinson Disease diagnosis, Parkinson Disease epidemiology, Neuroprotective Agents, Gout diagnosis, Gout epidemiology
- Abstract
Introduction: High levels of serum urate has been associated to a neuroprotective effect in Parkinson's disease (PD) as an antioxidant agent. However, the relation between gout and PD remains contradictory., Objective: To study if the neuroprotective effect of serum urate is maintained in patients with gout in a large urban Mediterranean population., Methods: Primary care based matched case-control study, carried out using an electronic health record database from the public primary care health system of Barcelona. The database contains anonymous data from 1,520,934 patients. All patients, over 40 years old, with a new diagnostic record of PD, or a new prescription of dopaminergic drugs were included (incident cases). We randomly selected four controls for each case, matched by gender and age, with the frequency matching approach. Retrospective data of PD risk factors were also collected for each individual. A multivariate logistic regression model was used to evaluate the association of gout and PD, adjusted by the presence of other risk factors., Results: A new PD diagnosis was found in 17,629 individuals (incident diagnosis rate of 2.2 per 1000 individuals). Multivariate logistic regression model showed for gout: aOR=0.83 (0.76-0.91). When stratified by age, aOR for those under 75years was 0.99 (0.85-1.16) and 75 or over OR=0.77 (0.70-0.86). Dyslipidemia, hypertension and diabetes mellitus were associated with an increased risk of PD. Tobacco consumption was protective., Conclusion: Our study, the first one made in a Mediterranean population, shows a PD protective effect of gout in both men and women over 75years old., (Copyright © 2022 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)
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- 2022
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24. Cutaneous adverse events with febuxostat after previous reactions to allopurinol: comment on the article by Singh and Cleveland.
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Quilis N, Vela P, Blanco Cáceres BA, Diaz-Torne C, Calvo-Aranda E, Sivera F, Prada-Ojeda A, Pérez Ruiz F, Pascual E, and Andrés M
- Subjects
- Allopurinol adverse effects, Febuxostat adverse effects, Gout Suppressants adverse effects, Humans, Gout drug therapy, Hyperuricemia drug therapy
- Abstract
Competing Interests: Competing interests: MA declares speaking fees and research grants from Grunenthal, Menarini and Horizon. The rest of the authors declare no conflicts of interest in the making of the present manuscript.
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- 2022
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25. Retention of golimumab treatment following discontinuation of non-TNF inhibitors in patients with inflammatory rheumatic diseases: An analysis of the Spanish BIOBADASER registry.
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Pombo-Suárez M, Sanchez-Piedra C, Ruiz-Montesino D, Diaz-Torne C, Jovaní V, Cea-Calvo L, and Castrejón I
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- Antibodies, Monoclonal therapeutic use, Humans, Registries, Tumor Necrosis Factor-alpha therapeutic use, Antirheumatic Agents therapeutic use, Rheumatic Diseases drug therapy
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- 2022
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26. Serum urate as a proposed surrogate outcome measure in gout trials: From the OMERACT working group.
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Morillon MB, Christensen R, Singh JA, Dalbeth N, Saag K, Taylor WJ, Neogi T, Kennedy MA, Pedersen BM, McCarthy GM, Shea B, Diaz-Torne C, Tedeschi SK, Grainger R, Abhishek A, Gaffo A, Nielsen SM, Noerup A, Simon LS, Lassere M, Tugwell P, Stamp LK, and Gout Working Group FTO
- Subjects
- Biomarkers, Gout Suppressants therapeutic use, Humans, Outcome Assessment, Health Care, Treatment Outcome, Gout, Uric Acid
- Abstract
Serum urate (SU) is the most common primary efficacy outcome in trials of urate-lowering therapies for gout. Despite this, it is not formally considered a validated surrogate outcome. In this paper we will outline the definitions of biomarkers and surrogate outcome measures, respectively as well as the available frameworks and challenges in the assessment of the validity of serum urate as a surrogate in gout (i.e. a reasonable replacement for gout symptoms)., Competing Interests: Declaration of Competing Interest MBM: No conflicts declared, RC: No conflicts declared, JAS: Has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc., Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Criteria subcommittee. Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response, ND: Reports consulting fees from AstraZeneca, Dyve BioSciences, Selecta, Horizon, and Arthrosi, speaker fees from Abbvie and Janssen, and research grants from Amgen and AstraZeneca, outside the submitted work. ORCID: 0000-0003-3485-0006, KS: Reports he is an Investigator for Horizon, Sobi, LG, Dyve and consulting fees from Horizon, WJT: No conflicts declared ORCID 0000-0001-6075-8479, TN: No conflicts declared. ORCID 000-002-9515-1711, MK: No conflicts declared ORCID 0000-0002-6445-8526, BMP: No conflicts declared, GMM: No conflicts declared, BJS: Is the senior Methodologist. ORCID 0000-0002-7686-2585, CDT: No conflicts declared. ORCID 0000-0001-6275-7699, SKT: No conflicts declared, RG: personal fees from Pfizer, Cornerstones, Jannsen, and Novartis. AA: No conflicts declared, ML: No conflicts declared, AG: No conflicts declared ORCID 0000-0001-7365-7212, LSS: Serves as a consultant to Horizon Therapeutics. He serves on the Executive of OMERACT and is Chair of the Finance Committee of OMERACT and Co-Chair of It's Business Advisory Committee., AN: No conflicts declared, SMN: No conflicts declared, ML: No conflicts declared, PT: No conflicts declared ORCID 00000-0001-5062-0556, LKS: No conflicts declared ORCID 0000-0003-0138-2912, (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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27. The inflammatory role of silent urate crystal deposition in intercritical gout.
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Diaz-Torne C, Ortiz MA, Garcia-Guillen A, Jeria-Navarro S, Sainz L, Fernandez-Sanchez S, Corominas H, and Vidal S
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- Adult, Aged, Aged, 80 and over, Case-Control Studies, Crystallization, Cytokines blood, Female, Humans, Male, Middle Aged, Secretome, Gout metabolism, Uric Acid
- Abstract
Objective: To study subclinical inflammation in intercritical gout patients and its relation to the estimated size of monosodium urate crystal deposition and cardiovascular risk factors., Methods: We performed a secretome analysis and the quantification of cytokine and adipokine plasma levels [IL-1β, IL-18, IL-6, soluble IL-6 receptor (sIL-6R), TNF-α, C-X-C motif chemokine 5, RANTES (Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted), leptin, resistin and adiponectin] to analyse subclinical inflammation in intercritical gout patients. Since it is currently not feasible to determinate the whole body deposit of monosodium urate crystals, we created an indirect clinical classification to estimate it. Then we compared cytokine levels in controls and gout patients and in patients with different crystal deposition sizes. We also studied the association between cytokine-levels and the number of cardiovascular risk factors., Results: Ninety consecutive patients attending a crystal arthritis unit were studied. IL-18, sIL-6R, RANTES, leptin and adiponectin were higher in intercritical gout patients than in controls. An association was observed between IL-18, sIL6-R and RANTES levels and the size of crystal deposition. IL-18, sIL6-R, RANTES and leptin were higher in patients with no cardiovascular risk factors compared with controls with no risk factors., Conclusion: Our results showed that the levels of some pro-inflammatory cytokines and metabolic proteins are elevated in intercritical gout patients. The levels of certain cytokines were related to the estimated size of the monosodium urate crystal deposition and to the number of cardiovascular risk factors. These cytokine changes may help to explain the increase in cardiovascular events in gout patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2021
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28. Metabolomics profiling predicts outcome of tocilizumab in rheumatoid arthritis: an exploratory study.
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Murillo-Saich JD, Diaz-Torne C, Ortiz MA, Coras R, Gil-Alabarse P, Pedersen A, Corominas H, Vidal S, and Guma M
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- 3-Hydroxybutyric Acid, Antibodies, Monoclonal, Humanized, Humans, Metabolomics, Phenylalanine, Phosphorylcholine, Tryptophan, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid
- Abstract
Introduction: To study metabolic signatures can be used to identify predictive biomarkers for a patient's therapeutic response., Objectives: We hypothesized that the characterization of a patients' metabolic profile, utilizing one-dimensional nuclear magnetic resonance (
1 H-NMR), may predict a response to tocilizumab in patients with rheumatoid arthritis (RA)., Methods: 40 active RA patients meeting the 2010 ACR/EULAR classification criteria initiating treatment with tocilizumab were recruited. Clinical outcomes were determined at baseline, and after six and twelve months of treatment. EULAR response criteria at 6 and 12 months to categorize patients as responders and non-responders. Blood was collected at baseline and after six months of tocilizumab therapy.1 H-NMR was used to acquire a spectra of plasma samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification. SPSS v.27 and MetaboAnalyst 4.0 were used for statistical and pathway analysis., Results: Isobutyrate, 3-hydroxybutyrate, lysine, phenylalanine, sn-glycero-3-phosphocholine, tryptophan and tyrosine were significantly elevated in responders at the baseline. OPLS-DA at baseline partially discriminated between RA responders and non-responders. A multivariate diagnostic model showed that concentrations of 3-hydroxybutyrate and phenylalanine improved the ability to specifically predict responders classifying 77.1% of the patients correctly. At 6 months, levels of methylamine, sn-glycero-3-phosphocholine and tryptophan tended to still be low in non-responders., Conclusion: The relationship between plasma metabolic profiles and the clinical response to tocilizumab suggests that1 H-NMR may be a promising tool for RA therapy optimization. More studies are needed to determine if metabolic profiling can predict the response to biological therapies in RA patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)- Published
- 2021
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29. Towards development of core domain sets for short term and long term studies of calcium pyrophosphate crystal deposition (CPPD) disease: A framework paper by the OMERACT CPPD working group.
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Cai K, Fuller A, Zhang Y, Hensey O, Grossberg D, Christensen R, Shea B, Singh JA, McCarthy GM, Rosenthal AK, Filippou G, Taylor WJ, Diaz-Torne C, Stamp LK, Edwards NL, Pascart T, Becce F, Nielsen SM, Tugwell P, Beaton D, Abhishek A, Tedeschi SK, and Dalbeth N
- Subjects
- Calcium Pyrophosphate, Humans, Calcinosis, Chondrocalcinosis, Osteoarthritis, Rheumatology
- Abstract
Introduction: Although calcium pyrophosphate deposition (CPPD) is common, there are no published outcome domains or validated measurement instruments for CPPD studies. In this paper, we describe the framework for development of the Outcome Measures in Rheumatology (OMERACT) CPPD Core Domain Sets., Methods: The OMERACT CPPD working group performed a scoping literature review and qualitative interview study. Generated outcomes were presented at the 2020 OMERACT CPPD virtual Special Interest Group (SIG) meeting with discussion focused on whether different core domain sets should be developed for different calcium pyrophosphate deposition (CPPD) clinical presentations and how the future CPPD Core Domain Set may overlap with already established osteoarthritis (OA) domains. These discussions informed development of a future work plan for development of the OMERACT CPPD Core Domain Sets., Findings: Domains identified from a scoping review of 112 studies and a qualitative interview study of 36 people (28 patients with CPPD, 7 health care professionals, one stakeholder) were mapped to core areas of OMERACT Filter 2.1. The majority of SIG participants agreed there was need to develop separate core domain sets for "short term" and "long term" studies of CPPD. Although CPPD + OA is common and core domain sets for OA have been established, participants agreed that existing OA core domain sets should not influence the development of OMERACT core domain sets for CPPD. Prioritization exercises (using Delphi methodology) will consider 40 potential domains for short term studies of CPPD and 47 potential domains for long term studies of CPPD., Conclusion: Separate OMERACT CPPD Core Domain Sets will be developed for "short term" studies for an individual flare of acute CPP crystal arthritis and for "long term" studies that may include participants with any clinical presentation of CPPD (acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and/or CPPD + OA)., Competing Interests: Declaration of Competing Interest KC reports a research fellowship grant from Arthritis Australia. RC is a member of the Technical Advisory Group of OMERACT. JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of OMERACT. DG has a private equity holding in Charlotte's Web Holdings, Inc. ND reports grants and personal fees from AstraZeneca, grants from Amgen, personal fees from Dyve, personal fees from Hengrui, personal fees from Selecta, personal fees from Horizon, personal fees from Abbvie, personal fees from Pfizer, personal fees from Janssen, personal fees from Arthrosi, outside the submitted work. AA and SKT have received consultant fees from NGM Biopharmaceuticals. FB has received personal consultant fees from Horizon Therapeutics. OMERACT, an organization that develops outcome measures in rheumatology, receives arms-length funding from 8 companies. The other authors have no disclosures., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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30. [The role of primary care in the COVID-19 crisis. Experience of an urban Primary Care team].
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Pou MA, Gayarre R, Ferrer-Moret S, Fernández-San-Martín MI, Feijoo MV, and Diaz-Torne C
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, COVID-19 diagnosis, COVID-19 epidemiology, Comorbidity, Female, Humans, Male, Middle Aged, Outcome and Process Assessment, Health Care, Pandemics, Primary Health Care methods, Primary Health Care statistics & numerical data, Referral and Consultation statistics & numerical data, Severity of Illness Index, Spain epidemiology, Urban Health Services statistics & numerical data, Young Adult, COVID-19 therapy, Hospitalization statistics & numerical data, Patient Care Team organization & administration, Primary Health Care organization & administration, Referral and Consultation organization & administration, Urban Health Services organization & administration
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- 2021
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31. Experience and impact of crystal pyrophosphate deposition (CPPD) from a patient and caregiver perspective: A qualitative exploration from the OMERACT CPPD working group.
- Author
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Fuller A, Cai K, Filippou G, Pascart T, Diaz-Torne C, Hensey O, Grossberg D, Christensen R, Shea B, Singh JA, Tedeschi SK, Dalbeth N, and Abhishek A
- Subjects
- Calcium Pyrophosphate, Caregivers, Diphosphates, Humans, Calcinosis, Chondrocalcinosis
- Abstract
Objective: To explore the lived experience of people with calcium pyrophosphate deposition (CPPD) disease and the impact of this condition on their daily lives., Methods: Patients with CPPD and their caregivers were invited to take part in a one-to-one (patient only) or paired (patient and caregiver) semi-structured interview. Interviews covered patients' diagnosis and treatment experiences, and the impact of CPPD on their daily lives. Transcribed interviews were analysed using inductive thematic analysis., Results: 28 patient interviews, six of which included a caregiver, were conducted across five countries. Acute CPP crystal arthritis flares resulted in temporary but profound disability for most patients, disrupting their ability to go about day-to-day activities, and they sought immediate medical attention. CPPD+OA and chronic CPP crystal inflammatory arthritis presented patients with longer term limitations in daily lives. Patients and their caregivers described these disruptions and limitations, which included a reduced ability or inability to complete household and self-care tasks, exercise, socialise, work and drive. They also described how arthritis pain and resulting limitations adversely impacted upon patients' psychological wellbeing. Delays in referral to specialists and diagnostic uncertainty were described by many. Lack of appropriate treatment or access to treatments only upon worsening of symptoms impacted upon the length of time some patients spent in pain and with functional limitations., Conclusion: This study is the first to demonstrate the wide-ranging impact of CPPD, and highlights the need for improved diagnosis, physician training, as well as greater emphasis upon finding targeted therapies to specifically treat CPPD., Competing Interests: Declaration of Competing Interest AF, CDT, GF, TP, OH, BS and ND have no disclosures. KC reports a research fellowship grant from Arthritis Australia. RC is a member of the Technical Advisory Group of OMERACT and JAS is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from eight companies. JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications; and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. DG has a private equity holding in Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee. AA and SKT have received consultant fees from NGM Biopharmaceuticals., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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32. Outcome domains reported by patients, caregivers, healthcare professionals and stakeholders for calcium pyrophosphate deposition (CPPD): A content analysis based on semi-structured qualitative interviews from the OMERACT CPPD working group.
- Author
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Fuller A, Cai K, Diaz-Torne C, Filippou G, Pascart T, Hensey O, Grossberg D, Christensen R, Shea B, Singh JA, Tedeschi SK, Dalbeth N, and Abhishek A
- Subjects
- Calcium Pyrophosphate, Caregivers, Delivery of Health Care, Humans, Chondrocalcinosis, Rheumatology
- Abstract
Introduction: Although calcium pyrophosphate deposition (CPPD) disease is common, there are no validated outcome measures for clinical research in this condition. The aim of this study was to generate a list of outcome domains as reported by patients, their caregivers, healthcare professionals (HCPs) and stakeholders to inform the development of an Outcome Measures in Rheumatology (OMERACT) Core Domain Set for CPPD., Methods: Patients with CPPD and their caregivers, HCPs and stakeholders took part in semi-structured qualitative interviews to explore potential outcome domains for CPPD clinical research relevant to their lived experience and knowledge of CPPD. Interviews were conducted in six countries across three continents. Data was analysed using manifest content analysis to identify outcome domains, which were tabulated and mapped to the core areas as defined by the OMERACT Filter 2.1., Results: Thirty-six interviews were conducted in total. Participants comprised of 28 patients (six of which included a caregiver), seven HCPs and one stakeholder. The commonly identified (sub-) domains (d) across the 1) abnormalities/manifestations core area were joint pain (d = 35), joint swelling (d = 27), joint stiffness (d = 25), CPPD flares (d = 25); 2) life-impact core area were overall function (d=35), and specifically the ability to complete daily tasks (d = 25); and 3) societal/resource use core area were use of analgesic medicines (d = 26). Patients more commonly reported joint swelling, stiffness and range of movement, and use of analgesics while HCPs more commonly reported domains relating to presence of CPP crystals, radiologic calcification, joint damage, time to diagnosis and suitability of treatment., Conclusion: Among a number of potential outcome domains identified, articular manifestations, function and analgesic use were most frequently mentioned by participants. These findings will be used to develop an OMERACT Core Domain Set for CPPD., Competing Interests: Declaration of Competing Interest AF, CDT, GF, TP, OH, DG, BS, SKT, ND and AA have no disclosures. KC reports a research fellowship grant from Arthritis Australia. RC is a member of the Technical Advisory Group of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, UBM LLC, Trio health, Medscape, WebMD, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, Practice Point communications, the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in Amarin pharmaceuticals and Viking therapeutics. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of OMERACT, an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. JAS serves on the FDA Arthritis Advisory Committee. JAS is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JAS is the editor and the Director of the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. JAS previously served as a member of the following committees: member, the American College of Rheumatology's (ACR) Annual Meeting Planning Committee (AMPC) and Quality of Care Committees, the Chair of the ACR Meet-the-Professor, Workshop and Study Group Subcommittee and the co-chair of the ACR Criteria and Response Criteria subcommittee., (Copyright © 2021 Elsevier Inc. All rights reserved.)
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- 2021
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33. Rheumatoid Arthritis: Defining Clinical and Ultrasound Deep Remission.
- Author
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Hèctor C, Millan AM, and Diaz-Torne C
- Abstract
The prognosis of patients with rheumatoid arthritis (RA) has improved substantially in the last two decades due to the appearance of biological therapies, but above all, due to the improvement in the strategy and management of the disease. Our goal in RA should be to achieve remission, or in its absence, the lowest inflammatory activity. Achieving remission will prevent from structural and functional damage highly associated with RA itself. Clinical remission is defined as the absence of significant signs and symptoms of inflammatory disease activity, as well as the abrogation of any signs of systemic inflammation. Currently, there are some controversies about remission. Which is the real remission? Which remission criteria should be used and when? Does clinical remission mean ultrasound remission? In the present review, we try to answer and put some light into it, focusing on clinical and ultrasound deep remission., (© 2020 The Mediterranean Journal of Rheumatology (MJR).)
- Published
- 2020
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34. Clinical features and outcomes of COVID-19 in patients with rheumatic diseases treated with biological and synthetic targeted therapies.
- Author
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Sanchez-Piedra C, Diaz-Torne C, Manero J, Pego-Reigosa JM, Rúa-Figueroa Í, Gonzalez-Gay MA, Gomez-Reino J, and Alvaro-Gracia JM
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized therapeutic use, Arthritis, Rheumatoid complications, Arthritis, Rheumatoid drug therapy, Betacoronavirus, COVID-19, Coronavirus Infections complications, Coronavirus Infections physiopathology, Female, Glucocorticoids therapeutic use, Hospitalization statistics & numerical data, Humans, Hydroxychloroquine therapeutic use, Intensive Care Units, Interleukin 1 Receptor Antagonist Protein therapeutic use, Janus Kinase Inhibitors therapeutic use, Male, Methotrexate therapeutic use, Middle Aged, Pandemics, Pneumonia, Viral complications, Pneumonia, Viral physiopathology, Rheumatic Diseases complications, Rituximab therapeutic use, SARS-CoV-2, Spain, Spondylarthropathies complications, Spondylarthropathies drug therapy, Tumor Necrosis Factor Inhibitors therapeutic use, Antirheumatic Agents therapeutic use, Coronavirus Infections mortality, Pneumonia, Viral mortality, Rheumatic Diseases drug therapy
- Abstract
Competing Interests: Competing interests: None declared.
- Published
- 2020
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35. A treat-to-target approach for gout confers renoprotective effect in patients with chronic kidney disease stage 3.
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Novella-Navarro M, Cabrera-Alarcon JL, Diaz-Torne C, Aramburu-Muñoz F, Janta I, Ortega de la O MC, Prada-Ojeda A, Sala-Icardo L, Urruticoechea-Arana A, García de la Peña Lefebvre P, and Calvo-Aranda E
- Subjects
- Aged, Aged, 80 and over, Alcohol Drinking, Colchicine therapeutic use, Female, Gout blood, Gout complications, Humans, Linear Models, Male, Middle Aged, Patient Care Planning, Renal Insufficiency, Chronic complications, Retrospective Studies, Smoking, Treatment Outcome, Uric Acid blood, Xanthine Oxidase antagonists & inhibitors, Allopurinol therapeutic use, Febuxostat therapeutic use, Glomerular Filtration Rate, Gout drug therapy, Gout Suppressants therapeutic use, Renal Insufficiency, Chronic metabolism
- Abstract
The aim of this study was to assess changes in the estimated glomerular filtration rate (eGFR) in gouty patients with chronic kidney disease (CKD) using a "treat-to-target" (T2T) approach in gout. This multicenter observational retrospective study included patients diagnosed with gout and CKD stage 3 taking xanthine oxidase inhibitors (XOIs) (allopurinol or febuxostat) for at least 12 months. All patients were treated using a T2T strategy according to national gout guidelines to achieve the target levels of serum uric acid (sUA; < 5-6 mg/dl) within 6 months of the first visit. The primary outcome was to assess changes in eGFR. The effects of independent variables were analyzed over eGFR in a linear mixed-effects (LME) model. Fifty patients with gout and CKD stage 3 treated with XOIs with a T2T strategy for 12 months were included. Eighty-two percent of the patients achieved the sUA target during the study period. The improvement seen in eGFR was higher during the first 6 months, showing a median increase of 7.54 ml/min/m
2 (SE = 1.25) and trending towards stability over 12 months. For every 1 mg/dl of decrease in sUA, an improvement of 1.5 ml/min/m2 in eGFR was observed (coefficient ± SE: - 1.58 ± 0.26) (p < 0.001) with no differences between type and dosage of XOIs treatment, colchicine administration, age, sex, and smoking status. A reduction in sUA levels using a T2T approach with XOIs at an optimal dose is possible and could help conserve and improve renal function in gouty patients with CKD stage 3.- Published
- 2020
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36. The combination of IL-6 and its soluble receptor is associated with the response of rheumatoid arthritis patients to tocilizumab.
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Diaz-Torne C, Ortiz MDA, Moya P, Hernandez MV, Reina D, Castellvi I, De Agustin JJ, Fuente D, Corominas H, Sanmarti R, Zamora C, Cantó E, and Vidal S
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- Adult, Aged, Arthritis, Rheumatoid drug therapy, Female, Humans, Male, Middle Aged, Antibodies, Monoclonal, Humanized therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid blood, Interleukin-6 blood, Receptors, Interleukin-6 blood
- Abstract
Background: IL-6 contributes significantly to the chronic inflammatory process of rheumatoid arthritis (RA). Tocilizumab, a humanized anti-human IL-6 receptor antibody that blocks the signaling originated by the IL-6/IL-6R complex, is an effective treatment. However, predictors of the response to tocilizumab are still required. We aimed to combine IL-6 and soluble IL-6R (sIL-6R) levels to identify groups of responses., Methods: Heparinized blood and clinical data from 63 RA patients were collected before treatment and after 3 and 6 months. Two-step clustering (SPSS v.18) was used to establish the relationship between IL-6 and sIL-6R. Then, we compared European League Against Rheumatism (EULAR) response criteria with remission achievement in the groups of patients., Results: Three statistical significant clusters of RA patients (i.e., g1, g2, and g3) were defined by serum concentrations of IL-6 and sIL-6R at baseline. All groups of RA patients had higher IL-6 and sIL-6R levels than healthy donors. The levels of IL-6 expressed as median (IQR) in g1 patients were 124(90-183)pg/ml, in g2 12.3(4.4-24)pg/ml, and in g3 60.1(30-146)pg/ml (p < 0.001). The levels of sIL-6R expressed as mean ± sd in g1 patients were 250.5 ± 72ng/ml, in g2 269.1 ± 125ng/ml, and in g3 732.7 ± 243ng/ml (p < 0.001). Disease activity score (DAS)28, C-reactive protein, and erythrocyte sedimentation rate were comparable in the three groups at baseline. Disease duration in g3 was the longest (median(IQR) years: g1 = 11(5-15), g2 = 12(8-20), and g3 23(16-26); p = 0.006), with years of disease evolution being correlated with sIL-6R levels (R = 0.417, p < 0.001). Simple and Clinical Disease Activity Index (SDAI and CDAI) decreased significantly in the three groups. However, EULAR response criteria and remission achievement at 6m was different in the three groups (p = 0.03 and 0.04, respectively). In all. 17 out of the 18 patients in g1 had a good or moderate response to tocilizumab. Conversely, the percentage of patients with no response to tocilizumab was higher in g3 than in g1 and g2. We also observed different changing patterns of IL-6 and sIL-6R levels among the three groups., Conclusions: RA patients could be easily stratified prior to therapeutic intervention with two molecules related to the pathway blocked by tocilizumab. G1 patients, who had the best response to tocilizumab, had the highest level of IL-6 and the lowest level of sIL-6R., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2018
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37. Improvement in Diagnosis and Treat-to-Target Management of Hyperuricemia in Gout: Results from the GEMA-2 Transversal Study on Practice.
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Perez Ruiz F, Sanchez-Piedra CA, Sanchez-Costa JT, Andrés M, Diaz-Torne C, Jimenez-Palop M, De Miguel E, Moragues C, and Sivera F
- Abstract
Introduction: The objective of the study was to evaluate changes regarding main European League Against Rheumatism (EULAR) recommendations on diagnosis and treatment of gout compared to a previous assessment., Methods: The GEMA-2 (Gout Evaluation and MAnagement) is a transversal assessment of practice for gout by rheumatologists. Main outcome variables were improvement of the previous GEMA assessment regarding the rate of crystal-proven diagnosis and that reaching therapeutic serum urate target below 6 mg/dl at last visit. Other management variables (prophylaxis, treatment of flares, lifestyle change advice) were also evaluated along with general characteristics. The sample was powered to include at least 483 patients for up to 50% change., Results: Data on management of 506 patients were retrieved from 38 out of 41 rheumatology units that participated in the previous GEMA audit. Crystal-proved diagnosis rate increased from 26% to 32% (31% improvement) and was higher in gout-dedicated practices; ultrasonography contributed to diagnosis in less than 1% of cases. Therapeutic serum urate at last visit improved from 41% to 64% of all patients (66% of patients on urate-lowering medications), in any case over 50% improvement from the previous assessment. The use of any urate-lowering medication available was not prescribed as per label dosing in patients who failed to achieve target serum urate. Clinical inertia to increase doses of either allopurinol or febuxostat was still present in clinical practice., Conclusion: Over 50% improvement in targeting therapeutic serum urate has been observed, but clinical inertia is still present. Diagnosis is still mostly clinically based, ultrasonography not being commonly contributive., Funding: Menarini España.
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- 2018
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38. Imaging as an Outcome Measure in Gout Studies: Report from the OMERACT Gout Working Group.
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Grainger R, Dalbeth N, Keen H, Durcan L, Lawrence Edwards N, Perez-Ruiz F, Diaz-Torne C, Singh JA, Khanna D, Simon LS, and Taylor WJ
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- Absorptiometry, Photon methods, Absorptiometry, Photon standards, Consensus Development Conferences as Topic, Diagnostic Imaging standards, Female, Gout pathology, Humans, Magnetic Resonance Imaging methods, Male, Multimodal Imaging methods, Multimodal Imaging standards, Radiography methods, Radiography standards, Tomography, X-Ray Computed methods, Tomography, X-Ray Computed standards, Ultrasonography, Doppler methods, Diagnostic Imaging methods, Gout diagnosis, Outcome Assessment, Health Care, Practice Guidelines as Topic, Uric Acid metabolism
- Abstract
Objective: The gout working group at the Outcome Measures in Rheumatology (OMERACT) 12 meeting in 2014 aimed to determine which imaging modalities show the most promise for use as measurement instruments for outcomes in studies of people with chronic gout and to identify the key foci for future research about the performance of these imaging techniques with respect to the OMERACT filter 2.0., Methods: During the gout session, a systematic literature review of the data addressing imaging modalities including plain radiography (XR), conventional computed tomography (CT), dual-energy computed tomography (DECT), magnetic resonance imaging (MRI), and ultrasound (US) and the fulfillment of the OMERACT filter 2.0 was presented., Results: The working group identified 3 relevant domains for imaging in gout studies: urate deposition (tophus burden), joint inflammation, and structural joint damage., Conclusion: The working group prioritized gaps in the data and identified a research agenda.
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- 2015
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39. The burden of disease in Spain: results from the global burden of disease study 2010.
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Haro JM, Tyrovolas S, Garin N, Diaz-Torne C, Carmona L, Sanchez-Riera L, Perez-Ruiz F, and Murray CJ
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- Adolescent, Adult, Aged, Aged, 80 and over, Cause of Death, Child, Child, Preschool, Chronic Disease, Cost of Illness, Female, Global Health, Humans, Infant, Infant, Newborn, Male, Middle Aged, Risk Factors, Spain, Disabled Persons statistics & numerical data, Health Status Indicators, Quality-Adjusted Life Years
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Background: We herein evaluate the Spanish population's trends in health burden by comparing results of two Global Burden of Diseases, Injuries, and Risk Factors Studies (the GBD studies) performed 20 years apart., Methods: Data is part of the GBD study for 1990 and 2010. We present results for mortality, years of life lost (YLLs), years lived with disability, and disability-adjusted life years (DALYs) for the Spanish population. Uncertainty intervals for all measures have been estimated., Results: Non-communicable diseases accounted for 3,703,400 (95% CI 3,648,270-3,766,720) (91.3%) of 4,057,400 total deaths, in the Spanish population. Cardiovascular and circulatory diseases were the main cause of mortality among non-communicable diseases (34.7% of total deaths), followed by neoplasms (27.1% of total deaths). Neoplasms, cardiovascular and circulatory diseases, and chronic respiratory diseases were the top three leading causes for YLLs. The most important causes of DALYs in 2010 were neoplasms, cardiovascular and circulatory diseases, musculoskeletal disorders, and mental and behavioral disorders., Conclusions: Mortality and disability in Spain have become even more linked to non-communicable diseases over the last years, following the worldwide trends. Cardiovascular and circulatory diseases, neoplasms, mental and behavioral disorders, and neurological disorders are the leading causes of mortality and disability. Specific focus is needed from health care providers and policy makers to develop health promotion and health education programs directed towards non-communicable disorders.
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- 2014
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40. Adalimumab regulates intracellular TNFα production in patients with rheumatoid arthritis.
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Zamora-Atenza C, Diaz-Torne C, Geli C, Diaz-Lopez C, Ortiz MA, Moya P, Castellví I, Nieto JC, Cantó E, Casademont J, Juarez C, Llobet JM, and Vidal S
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- Adalimumab, Arthritis, Rheumatoid metabolism, Cell Membrane metabolism, Cytoplasm metabolism, Female, Flow Cytometry, Humans, Intracellular Space metabolism, Male, Middle Aged, Monocytes metabolism, Antibodies, Monoclonal, Humanized therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid immunology, Tumor Necrosis Factor-alpha biosynthesis
- Abstract
Introduction: Adalimumab is a fully human anti-tumor necrosis factor α (anti-TNFα) monoclonal antibody that specifically blocks the interaction of TNFα with its receptors. It binds both soluble and transmembrane TNFα. We hypothesized that blocking these TNFα signals regulates the altered TNFα production in rheumatoid arthritis (RA) patients., Methods: We compared, by flow cytometry, Toll-like receptor induction levels of membrane and intracellular TNFα in monocytes (iTNFα + CD14+ cells) from 12 patients before and after adalimumab treatment with those from 5 healthy donors., Results: Before starting the treatment, the percentage of iTNFα+ CD14+ cells in the RA patients was significantly lower than that in healthy donors (mean ± SEM = 33.16 ± 4.82% vs 66.51 ± 2.4%, P < 0.001). When we added in vitro TNFα to healthy donor culture cells, levels of iTNFα+ CD14+ cells decreased, suggesting that the TNFα signal was responsible for the iTNFα+ CD14+ cell downregulation observed in the RA patients. After 2, 6 and 12 adalimumab injections, we observed significant blocking of membrane and soluble TNFα and a progressive increase in iTNFα+ CD14+ cells in ten patients with a good to moderate response as defined by the European League Against Rheumatism (EULAR) criteria. Levels of iTNFα+ CD14+ cells after 12 injections in these 10 patients were comparable to levels in healthy donors. In two patients, iTNFα+ CD14+ cell upregulation was not observed, and their EULAR-defined responses had not improved. The first patient developed antiadalimumab antibodies, explaining why adalimumab was not able to block membrane and soluble TNFα. In the second patient, adalimumab was discontinued because of adverse effects, which led to a decrease in iTNFα+ CD14+ cells to levels measured before treatment., Conclusions: Our findings suggest that adalimumab treatment in RA patients can return iTNFα levels to those of healthy donors. This effect was not observed in the presence of neutralizing antiadalimumab antibodies.
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- 2014
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41. Concerns of patients with gout are incompletely captured by OMERACT-endorsed domains of measurement for chronic gout studies.
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Diaz-Torne C, Pou MA, Castellvi I, Corominas H, and Taylor WJ
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- Adult, Aged, Aged, 80 and over, Arthralgia physiopathology, Chronic Disease, Disability Evaluation, Female, Humans, Male, Middle Aged, Quality of Health Care, Quality of Life, Range of Motion, Articular physiology, Treatment Outcome, Gout physiopathology, Gout therapy, Health Status Indicators, Outcome Assessment, Health Care, Patient Participation
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Background: Appropriate evaluation of disease or treatment outcomes requires a good understanding of the aspects of the disease and its consequences that actually matter to patients. The OMERACT process has identified several domains of outcome measurement for chronic gout, but patient involvement has only been briefly described., Objectives: To make the results of patient involvement more explicit, the current study reports on an exercise carried out in the early part of the OMERACT domain identification process., Methods: Patients with gout were asked to identify areas of life affected by gout. These areas were rated (0-10) and ranked for importance by a second group of patients with gout recruited from both primary care and a rheumatology clinic., Results: Thirty-one patients with gout performed the initial generation of areas of importance. These areas were combined to form 14 items, which were ranked and scored by 107 patients. Four areas were ranked first to third most important by at least 20% of participants. These were pain (median rating, 10), loss of joint motion (median rating, 9), work loss (median rating, 7), and joint inflammation/swelling (median rating, 8). Three additional areas were ranked highly by at least 10% of patients: difficulty with wearing shoes, having to undertake a restrictive diet, and sleep., Conclusions: These data largely confirmed the relevance of the gout OMERACT domains while identifying additional issues for patients that require further investigation.
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- 2014
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42. Total knee arthroplasty in a patient with subcutaneous and intra-articular tophaceous gout--a case report.
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Aguilera X, Gonzalez JC, Celaya F, Jordan M, Diaz-Torne C, and Monllau JC
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- Aged, 80 and over, Biomechanical Phenomena, Gout diagnosis, Gout physiopathology, Humans, Knee Joint diagnostic imaging, Knee Joint physiopathology, Male, Radiography, Range of Motion, Articular, Recovery of Function, Treatment Outcome, Arthroplasty, Replacement, Knee, Gout surgery, Knee Joint surgery
- Abstract
Total knee arthroplasty is a common operation for all types of arthritis, including chronic gouty arthritis. Tophi deposits are a well-known cause of joint destruction, but simultaneous subcutaneous and articular tophaceous gout is exceptional. We report a patient who required bilateral total knee replacement for this rare condition.
- Published
- 2014
43. A delphi exercise to identify characteristic features of gout - opinions from patients and physicians, the first stage in developing new classification criteria.
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Prowse RL, Dalbeth N, Kavanaugh A, Adebajo AO, Gaffo AL, Terkeltaub R, Mandell BF, Suryana BP, Goldenstein-Schainberg C, Diaz-Torne C, Khanna D, Lioté F, Mccarthy G, Kerr GS, Yamanaka H, Janssens H, Baraf HF, Chen JH, Vazquez-Mellado J, Harrold LR, Stamp LK, Van De Laar MA, Janssen M, Doherty M, Boers M, Edwards NL, Gow P, Chapman P, Khanna P, Helliwell PS, Grainger R, Schumacher HR, Neogi T, Jansen TL, Louthrenoo W, Sivera F, Taylor WJ, and Alten R
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- Delphi Technique, Female, Health Surveys, Humans, Male, New Zealand, Patients, Physicians, Severity of Illness Index, Surveys and Questionnaires, Gout classification, Gout diagnosis
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Objective: To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout., Methods: Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index., Results: Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory., Conclusion: Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms.
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- 2013
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44. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
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Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabé E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fèvre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gosselin R, Grainger R, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Ma J, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O'Donnell M, O'Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leòn FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, Murray CJ, AlMazroa MA, and Memish ZA
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Prevalence, Sex Factors, Young Adult, Global Health statistics & numerical data, Health Status, Quality-Adjusted Life Years, Wounds and Injuries epidemiology
- Abstract
Background: Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs)., Methods: Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis., Findings: Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350,000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient -0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa., Interpretation: Rates of YLDs per 100,000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
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- 2012
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45. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010.
- Author
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Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S, Aboyans V, Abraham J, Ackerman I, Aggarwal R, Ahn SY, Ali MK, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Bahalim AN, Barker-Collo S, Barrero LH, Bartels DH, Basáñez MG, Baxter A, Bell ML, Benjamin EJ, Bennett D, Bernabé E, Bhalla K, Bhandari B, Bikbov B, Bin Abdulhak A, Birbeck G, Black JA, Blencowe H, Blore JD, Blyth F, Bolliger I, Bonaventure A, Boufous S, Bourne R, Boussinesq M, Braithwaite T, Brayne C, Bridgett L, Brooker S, Brooks P, Brugha TS, Bryan-Hancock C, Bucello C, Buchbinder R, Buckle G, Budke CM, Burch M, Burney P, Burstein R, Calabria B, Campbell B, Canter CE, Carabin H, Carapetis J, Carmona L, Cella C, Charlson F, Chen H, Cheng AT, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahiya M, Dahodwala N, Damsere-Derry J, Danaei G, Davis A, De Leo D, Degenhardt L, Dellavalle R, Delossantos A, Denenberg J, Derrett S, Des Jarlais DC, Dharmaratne SD, Dherani M, Diaz-Torne C, Dolk H, Dorsey ER, Driscoll T, Duber H, Ebel B, Edmond K, Elbaz A, Ali SE, Erskine H, Erwin PJ, Espindola P, Ewoigbokhan SE, Farzadfar F, Feigin V, Felson DT, Ferrari A, Ferri CP, Fèvre EM, Finucane MM, Flaxman S, Flood L, Foreman K, Forouzanfar MH, Fowkes FG, Fransen M, Freeman MK, Gabbe BJ, Gabriel SE, Gakidou E, Ganatra HA, Garcia B, Gaspari F, Gillum RF, Gmel G, Gonzalez-Medina D, Gosselin R, Grainger R, Grant B, Groeger J, Guillemin F, Gunnell D, Gupta R, Haagsma J, Hagan H, Halasa YA, Hall W, Haring D, Haro JM, Harrison JE, Havmoeller R, Hay RJ, Higashi H, Hill C, Hoen B, Hoffman H, Hotez PJ, Hoy D, Huang JJ, Ibeanusi SE, Jacobsen KH, James SL, Jarvis D, Jasrasaria R, Jayaraman S, Johns N, Jonas JB, Karthikeyan G, Kassebaum N, Kawakami N, Keren A, Khoo JP, King CH, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Laden F, Lalloo R, Laslett LL, Lathlean T, Leasher JL, Lee YY, Leigh J, Levinson D, Lim SS, Limb E, Lin JK, Lipnick M, Lipshultz SE, Liu W, Loane M, Ohno SL, Lyons R, Mabweijano J, MacIntyre MF, Malekzadeh R, Mallinger L, Manivannan S, Marcenes W, March L, Margolis DJ, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGill N, McGrath J, Medina-Mora ME, Meltzer M, Mensah GA, Merriman TR, Meyer AC, Miglioli V, Miller M, Miller TR, Mitchell PB, Mock C, Mocumbi AO, Moffitt TE, Mokdad AA, Monasta L, Montico M, Moradi-Lakeh M, Moran A, Morawska L, Mori R, Murdoch ME, Mwaniki MK, Naidoo K, Nair MN, Naldi L, Narayan KM, Nelson PK, Nelson RG, Nevitt MC, Newton CR, Nolte S, Norman P, Norman R, O'Donnell M, O'Hanlon S, Olives C, Omer SB, Ortblad K, Osborne R, Ozgediz D, Page A, Pahari B, Pandian JD, Rivero AP, Patten SB, Pearce N, Padilla RP, Perez-Ruiz F, Perico N, Pesudovs K, Phillips D, Phillips MR, Pierce K, Pion S, Polanczyk GV, Polinder S, Pope CA 3rd, Popova S, Porrini E, Pourmalek F, Prince M, Pullan RL, Ramaiah KD, Ranganathan D, Razavi H, Regan M, Rehm JT, Rein DB, Remuzzi G, Richardson K, Rivara FP, Roberts T, Robinson C, De Leòn FR, Ronfani L, Room R, Rosenfeld LC, Rushton L, Sacco RL, Saha S, Sampson U, Sanchez-Riera L, Sanman E, Schwebel DC, Scott JG, Segui-Gomez M, Shahraz S, Shepard DS, Shin H, Shivakoti R, Singh D, Singh GM, Singh JA, Singleton J, Sleet DA, Sliwa K, Smith E, Smith JL, Stapelberg NJ, Steer A, Steiner T, Stolk WA, Stovner LJ, Sudfeld C, Syed S, Tamburlini G, Tavakkoli M, Taylor HR, Taylor JA, Taylor WJ, Thomas B, Thomson WM, Thurston GD, Tleyjeh IM, Tonelli M, Towbin JA, Truelsen T, Tsilimbaris MK, Ubeda C, Undurraga EA, van der Werf MJ, van Os J, Vavilala MS, Venketasubramanian N, Wang M, Wang W, Watt K, Weatherall DJ, Weinstock MA, Weintraub R, Weisskopf MG, Weissman MM, White RA, Whiteford H, Wiebe N, Wiersma ST, Wilkinson JD, Williams HC, Williams SR, Witt E, Wolfe F, Woolf AD, Wulf S, Yeh PH, Zaidi AK, Zheng ZJ, Zonies D, Lopez AD, AlMazroa MA, and Memish ZA
- Subjects
- Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Middle Aged, Prevalence, Sex Factors, Young Adult, Global Health statistics & numerical data, Health Status, Quality-Adjusted Life Years, Wounds and Injuries epidemiology
- Abstract
Background: Measuring disease and injury burden in populations requires a composite metric that captures both premature mortality and the prevalence and severity of ill-health. The 1990 Global Burden of Disease study proposed disability-adjusted life years (DALYs) to measure disease burden. No comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study. We aimed to calculate disease burden worldwide and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time., Methods: We calculated DALYs as the sum of years of life lost (YLLs) and years lived with disability (YLDs). DALYs were calculated for 291 causes, 20 age groups, both sexes, and for 187 countries, and aggregated to regional and global estimates of disease burden for three points in time with strictly comparable definitions and methods. YLLs were calculated from age-sex-country-time-specific estimates of mortality by cause, with death by standardised lost life expectancy at each age. YLDs were calculated as prevalence of 1160 disabling sequelae, by age, sex, and cause, and weighted by new disability weights for each health state. Neither YLLs nor YLDs were age-weighted or discounted. Uncertainty around cause-specific DALYs was calculated incorporating uncertainty in levels of all-cause mortality, cause-specific mortality, prevalence, and disability weights., Findings: Global DALYs remained stable from 1990 (2·503 billion) to 2010 (2·490 billion). Crude DALYs per 1000 decreased by 23% (472 per 1000 to 361 per 1000). An important shift has occurred in DALY composition with the contribution of deaths and disability among children (younger than 5 years of age) declining from 41% of global DALYs in 1990 to 25% in 2010. YLLs typically account for about half of disease burden in more developed regions (high-income Asia Pacific, western Europe, high-income North America, and Australasia), rising to over 80% of DALYs in sub-Saharan Africa. In 1990, 47% of DALYs worldwide were from communicable, maternal, neonatal, and nutritional disorders, 43% from non-communicable diseases, and 10% from injuries. By 2010, this had shifted to 35%, 54%, and 11%, respectively. Ischaemic heart disease was the leading cause of DALYs worldwide in 2010 (up from fourth rank in 1990, increasing by 29%), followed by lower respiratory infections (top rank in 1990; 44% decline in DALYs), stroke (fifth in 1990; 19% increase), diarrhoeal diseases (second in 1990; 51% decrease), and HIV/AIDS (33rd in 1990; 351% increase). Major depressive disorder increased from 15th to 11th rank (37% increase) and road injury from 12th to 10th rank (34% increase). Substantial heterogeneity exists in rankings of leading causes of disease burden among regions., Interpretation: Global disease burden has continued to shift away from communicable to non-communicable diseases and from premature death to years lived with disability. In sub-Saharan Africa, however, many communicable, maternal, neonatal, and nutritional disorders remain the dominant causes of disease burden. The rising burden from mental and behavioural disorders, musculoskeletal disorders, and diabetes will impose new challenges on health systems. Regional heterogeneity highlights the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account. Because of improved definitions, methods, and data, these results for 1990 and 2010 supersede all previously published Global Burden of Disease results., Funding: Bill & Melinda Gates Foundation., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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46. Identification of broadly discriminatory tissue biomarkers of synovitis with binary and multicategory receiver operating characteristic analysis.
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Ogdie A, Li J, Dai L, Paessler ME, Yu X, Diaz-Torne C, Akmatov M, Schumacher HR, and Pessler F
- Subjects
- Antigens, CD20 immunology, Area Under Curve, Arthritis, Infectious immunology, Arthritis, Rheumatoid immunology, Biomarkers metabolism, CD3 Complex immunology, Humans, Osteoarthritis immunology, ROC Curve, Synovial Membrane immunology, von Willebrand Factor immunology, Antigens, CD immunology, Antigens, Differentiation, Myelomonocytic immunology, Ki-67 Antigen immunology, Lewis X Antigen immunology, Synovitis immunology
- Abstract
Immunohistochemical synovial tissue biomarkers are used increasingly to classify arthropathies, study their pathogenesis, and to measure disease activity in clinical trials. We have used receiver operating characteristic (ROC) analysis to quantify the discriminatory abilities of markers for common inflammatory cells (subintimal CD15, CD68, CD3, CD20, CD38, and lining CD68), proliferating cells (Ki-67) and blood vessels (von Willebrand factor, vWF) among inflammatory (chronic septic arthritis, early arthritis and rheumatoid arthritis (RA)) and degenerative arthropathies (osteoarthritis (OA) and orthopedic arthropathies) and normal synovium. Six of the eight markers distinguished accurately between RA and the degenerative arthropathies (area under the curve (AUC) 0.91-0.97), whereas subintimal CD68 (AUC 0.92) and Ki-67 (AUC 0.87) distinguished best between OA and normal synovium. Fold differences in mean expression correlated only modestly with AUCs (r(2) = 0.44). Multicategory ROC analysis ranked Ki-67, subintimal CD68, and CD15 as discriminating best among all six sample groups, and thus identified them as the most broadly applicable markers.
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- 2010
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47. Progress in measurement instruments for acute and chronic gout studies.
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Grainger R, Taylor WJ, Dalbeth N, Perez-Ruiz F, Singh JA, Waltrip RW, Schlesinger N, Evans R, Edwards NL, Sivera F, Diaz-Torne C, MacDonald PA, McQueen FM, and Schumacher HR
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- Acute Disease, Arthralgia physiopathology, Chronic Disease, Consensus Development Conferences as Topic, Disability Evaluation, Gout physiopathology, Gout psychology, Humans, Quality of Life, Uric Acid blood, Consensus, Gout diagnosis, Outcome Assessment, Health Care methods, Outcome Assessment, Health Care trends, Severity of Illness Index
- Abstract
Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling, joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some criteria of the OMERACT filter, but these require further work, particularly regarding sensitivity to change over shorter time periods. Priorities for future research include measurement of joint inflammation in acute gout and disability in acute and chronic gout.
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- 2009
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48. Outcome domains for studies of acute and chronic gout.
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Schumacher HR, Taylor W, Edwards L, Grainger R, Schlesinger N, Dalbeth N, Sivera F, Singh J, Evans R, Waltrip RW, Diaz-Torne C, MacDonald P, McQueen F, and Perez-Ruiz F
- Subjects
- Acute Disease, Arthralgia physiopathology, Chronic Disease, Disability Evaluation, Gout physiopathology, Gout psychology, Humans, Quality of Life, Uric Acid blood, Consensus, Gout diagnosis, Outcome Assessment, Health Care standards, Severity of Illness Index
- Abstract
Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life, activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study.
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- 2009
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49. Local cytokine profiles in knee osteoarthritis: elevated synovial fluid interleukin-15 differentiates early from end-stage disease.
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Scanzello CR, Umoh E, Pessler F, Diaz-Torne C, Miles T, Dicarlo E, Potter HG, Mandl L, Marx R, Rodeo S, Goldring SR, and Crow MK
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- Aged, Biomarkers metabolism, Humans, Immunohistochemistry, Male, Middle Aged, Severity of Illness Index, Cartilage, Articular pathology, Cytokines metabolism, Interleukin-15 metabolism, Osteoarthritis, Knee pathology, Synovial Fluid metabolism, Synovial Membrane pathology
- Abstract
Objective: Much of what is known about the inflammatory response in the synovial membrane (SM) of patients with osteoarthritis (OA) comes from studies of synovial tissues from end-stage disease. In this study, we sought to better characterize the inflammatory infiltrate in symptomatic patients with early signs of knee OA, and to determine how inflammatory cell populations relate to the pattern of cytokine and degradative enzyme production., Methods: Study populations comprised patients with degenerative meniscal tears and early cartilage thinning undergoing arthroscopic procedures (early OA) and patients undergoing total knee replacement for end-stage OA. Quantitative real-time polymerase chain reaction (PCR) was used to measure expression of SM cytokines and enzymes implicated in the pathogenesis of inflammatory arthritis and OA, as well as cell lineage-specific markers. We quantified synovial fluid (SF) cytokines and enzymes by enzyme-linked immunosorbent assay (ELISA) and SM cell populations by immunohistochemistry., Results: We found increased levels of SF interleukin-15 (IL-15) protein in the early knee OA patients when compared to end-stage OA. Both SF IL-15 protein and numbers of CD8 cells within SM correlated with matrix metalloproteinase-1 (MMP-1) and three levels. TNF-alpha, IL-6 and IL-21 were also detectable in the SF of the majority of patients, and IL-15 levels were associated with IL-6 levels., Conclusion: IL-15 is elevated in early knee OA, suggesting activation of an innate immune response in the SM. The association of IL-15 expression with CD8 transcripts and MMPs implicates this cytokine in OA pathogenesis and as a candidate therapeutic target.
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- 2009
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50. The arthritis of Antoni Gaudí.
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Azevedo VF and Diaz-Torne C
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- Architecture history, Art history, History, 19th Century, History, 20th Century, Spain, Arthritis, Juvenile history
- Abstract
Antoni Gaudí i Cornet, Catalan architect and one of the most important visual artists of the 19th and 20th centuries, suffered from a recurrent and often persistent arthritis since he was 6 years old. His diagnosis is uncertain but juvenile idiopathic arthritis is most likely. He coped successfully with his rheumatic illness during his life. It is proposed that his arthritis may have influenced him to the development of 2 of his major skills: observation power and analysis of nature.
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- 2008
- Full Text
- View/download PDF
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