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1.
Arthritis Rheumatol ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31612614

RESUMO

BACKGROUND: Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. We sought to determine whether any histologic features of synovium associate with this symptom. METHODS: Patient reports of morning stiffness duration, stiffness severity and disease activity scores (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Histopathology of synovium was scored for 10 features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells detritus, neutrophils and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays. RESULTS: Stiffness severity and morning stiffness duration were both significantly associated with DAS28 (p=0.0001 and p=0.001 respectively). None of the synovial features examined were associated with patient-reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly (P<0.0001) associated with patient report of greater than one hour of morning stiffness, such that 73% of patients with both synovial fibrin and neutrophils report more than one hour of morning stiffness. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells (p=0.008). DNase1 treatment of necrotic neutrophils abrogated the delay in fibrinolysis. CONCLUSION: In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiological phenomena.

2.
Rheumatol Int ; 39(10): 1789-1796, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31440812

RESUMO

Permanent vision loss is one of the most serious complications of giant cell arteritis (GCA) and therefore prompt diagnosis is paramount. However, diagnosis of GCA remains challenging due to its frequently non-specific presentation. Our aim was to identify differences in the characteristics of GCA patients with, and without, current visual symptoms. A cross-sectional survey was mailed to patients with a GCA Read code entered in their GP electronic medical record. Responders were categorised as those currently reporting a visual symptom or not. We compared general and GCA-specific characteristics in these two groups. The association of diagnostic delay with subsequent experience of visual symptoms was examined using unadjusted and adjusted linear regression analysis. 318 GCA patients responded to the survey (59.6%). Responders were predominantly female (69.8%), with a mean age of 73.7 years (SD 8.2). 28% reported current visual symptoms. There was no statistically significant difference in the general characteristics between those with and without visual symptoms. Of GCA-specific characteristics, pre-GCA diagnosis of diplopia (p = 0.018), temporary (p ≤ 0.001) or permanent visual problems (p = 0.001) and hoarseness (p = 0.004) were more common among those reporting current visual symptoms. There was no association between the extent of diagnostic delay and reporting of current visual symptoms. Though we found few characteristics to distinguish between GCA patients with or without current visual symptoms, diagnostic delay was not associated with current visual symptoms. Our findings highlighted the continued difficulty for clinicians to identify GCA patients at the highest risk of visual complications.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31325308

RESUMO

OBJECTIVES: PMR and GCA are associated with increased risk of vascular disease. However, it remains unclear whether this relationship is causal or reflects a common underlying propensity. The aim of this study was to identify whether known cardiovascular risk factors increase the risk of PMR and GCA. METHODS: Clinical records were examined using key word searches to identify cases of PMR and GCA, applying current classification criteria in a population-based cohort. Associations between cardiovascular risk factors and incident PMR and GCA were analysed using Cox proportional hazards. RESULTS: In 315 022 person years of follow-up, there were 395 incident diagnoses of PMR and 118 incident diagnoses of GCA that met the clinical definition. Raised diastolic blood pressure (>90 mmHg) at baseline/recruitment was associated with subsequent incident PMR [hazard ratio=1.35 (95% CI 1.01, 1.80) P=0.045], and ever-smoking was associated with incident GCA [hazard ratio=2.01 (95% CI 1.26, 3.20) P=0.003]. Estimates were similar when the analysis was restricted to individuals whose diagnoses satisfied the current classification criteria sets. CONCLUSION: PMR and GCA shares common risk factors with vascular disease onset, suggesting a common underlying propensity. This may indicate a potential for disease prevention strategies through modifying cardiovascular risk.

5.
J Rheumatol ; 46(10): 1360-1364, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30709960

RESUMO

OBJECTIVE: To report the progress of the Outcome Measures in Rheumatology (OMERACT) Polymyalgia Rheumatica (PMR) Working Group in selecting candidate instruments for a core outcome measurement set. METHODS: A systematic literature review identified outcomes measured and instruments used in PMR studies, and a respondent survey and raw data analysis assessed their domain match and feasibility. RESULTS: Candidate instruments were identified for pain [visual analog scale/numerical rating scale (VAS/NRS)], stiffness (VAS/NRS and duration), and physical function (Health Assessment Questionnaire-Disability Index/modified Health Assessment Questionnaire). Domain match and feasibility assessments were favorable; however, validation in PMR was lacking. CONCLUSION: Further assessment of candidate instruments is required prior to recommending a PMR core outcome measurement set.

6.
Clin Exp Rheumatol ; 37 Suppl 117(2): 104-108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30767870

RESUMO

OBJECTIVES: We propose a GCA probability score intended to help to risk-stratify patients referred by general practitioners with suspected GCA into those with high probability of GCA versus low probability of GCA. In this pilot study we evaluated the diagnostic accuracy of this proposed scoring system. METHODS: A scoring system was proposed based on clinical experience. Retrospective analysis was conducted from clinical notes of consecutive patients presenting to a Fast Track Pathway clinic between August 2016 and August 2017. The GCA Probability Score was calculated for each patient and receiver operating characteristic (ROC) curve plotted. RESULTS: Of 122 consecutive patients, full data were available for calculation of GCA probability score in all patients except one (excluded from this analysis). The area under the ROC curve was 0.953 (95% confidence interval: 0.911, 0.994). The ROC curve showed an optimal cut point of 9.5 out of a possible score of 32. At this cut-point there was a sensitivity of 95.7% and specificity 86.7%, and 88.4% of cases were correctly classified. CONCLUSIONS: The GCA Probability Score is a promising and feasible tool for risk stratification of patients referred by general practitioners with suspected GCA. In a fast track clinic setting this aids exclusion of GCA in low probability cases and confirmation of disease in high probability disease. Refinement and subsequent external validation of this score is required.


Assuntos
Arterite de Células Gigantes , Arterite de Células Gigantes/diagnóstico , Humanos , Projetos Piloto , Probabilidade , Curva ROC , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade
7.
J Rheumatol ; 46(9): 1179-1182, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30647165

RESUMO

OBJECTIVE: To understand the effects of glucocorticoids (GC), which are of importance to patients. METHODS: The results of 2 literature reviews, a patient survey, and a qualitative study were presented. RESULTS: No validated instrument exists to evaluate GC effect on patients. Survey data revealed skin thinning/bruising, sleep disturbance, and weight gain as the most frequent adverse effects. The qualitative research yielded rich data covering rapid benefits and physical and emotional consequences of GC. CONCLUSION: It was agreed that a patient-reported outcome to measure GC effect was required and a research agenda was developed for this goal.

8.
J Rheumatol ; 46(8): 1053-1058, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30647191

RESUMO

OBJECTIVE: Outcome Measures in Rheumatology (OMERACT) convened a premeeting in 2018 to bring together patients, regulators, researchers, clinicians, and consumers to build upon previous OMERACT drug safety work, with patients fully engaged throughout all phases. METHODS: Day 1 included a brief introduction to the history of OMERACT and methodology, and an overview of current efforts within and outside OMERACT to identify patient-reported medication safety concerns. On Day 2, two working groups presented results; after each, breakout groups were assembled to discuss findings. RESULTS: Five themes pertaining to drug safety measurement emerged. CONCLUSION: Current approaches have failed to include data from the patient's perspective. A better understanding of how individuals with rheumatic diseases view potential benefits and harms of therapies is essential.

11.
Br J Radiol ; 91(1089): 20180247, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29927635

RESUMO

OBJECTIVE: Large-vessel vasculitis (LVV) is a serious illness with potentially life-threatening consequences. (18Fluorine) fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) has emerged as a valuable diagnostic tool in suspected LVV, combining the strengths of functional and structural imaging. This study aimed to compare the accuracy of FDG PET-CT and contrast-enhanced CT (CECT) in the evaluation of patients with LVV. METHODS: A retrospective database review for LVV patients undergoing CECT and PET-CT between 2011 to 2016 yielded demographics, scan interval and vasculitis type. Qualitative and quantitative PET-CT analyses included aorta:liver FDG uptake, bespoke FDG uptake distribution scores and vascular maximum standardised uptake values (SUVmax). Quantitative CECT data were assessed for wall thickness and mural-lumen ratio. Receiver operating characteristics (ROC) curves were constructed to evaluate comparative diagnostic accuracy and a correlational analysis was conducted between SUVmax and wall thickness. RESULTS: 36 adults (17 LVV, 19 controls) with a mean age (range) 63 (38-89) years, of which 17 (47%) were males were included. Time interval between CT and PET was mean [standard deviation (SD)] 1.9 (1.2) months. Both SUVmax and wall thickness demonstrated a significant difference between LVV and controls, with a mean difference [95%confidence interval (CI)] for SUVmax 1.6 (1.1, 2.0) and wall thickness 1.25 (0.68, 1.83) mm, respectively. These two parameters were significantly correlated (p < 0.0001, R = 0.62). The area under the curve (AUC) (95% CI) for SUVmax was 0.95 (0.88-1.00), and for mural thickening was 0.83 (0.66-0.99). CONCLUSION: FDG PET-CT demonstrated excellent accuracy whilst CECT mural thickening showed good accuracy in the diagnosis of LVV. Both parameters showed a highly significant correlation. In hospitals without access to FDG PET-CT or in patients unsuitable for PET-CT (e.g. uncontrolled diabetes) CECT offers a viable alternative for the assessment of LVV. Advances in knowledge: FDG PET-CT is a highly accurate test for the diagnosis of LVV. Aorta:liver SUVmax ratio is the most specific parameter for LVV. In hospitals without PET-CT or in unsuitable patients e.g. diabetics, CECT is a viable alternative.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Vasculite/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta/diagnóstico por imagem , Aorta/metabolismo , Estudos de Casos e Controles , Meios de Contraste , Feminino , Fluordesoxiglucose F18/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
12.
Gait Posture ; 61: 339-345, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29427859

RESUMO

BACKGROUND: Activity monitors provide objective measurements of physical activity, however, the accuracy of these devices in people with polymyalgia rheumatica (PMR) is unknown. Therefore, this study aimed to obtain preliminary evidence of the accuracy of two activity monitors and explore if clinical and gait-related factors altered device accuracy in people with PMR. METHODS: The ActiGraph with low frequency extension (+LFE) and standard (-LFE) algorithms, Fitbit-Zip (waist) and Fitbit-Zip (shirt) were concurrently tested using a two-minute walk test (2MWT) and stairs test in 27 people with PMR currently treated with prednisolone. To determine accuracy, activity monitor step-count was compared to a gold-standard step-count (GSSC; calculated from video recording) using Bland-Altman plots. RESULTS: The Fitbit-Zip (waist) achieved closest agreement to the GSSC for the 2MWT (mean bias (95%CI): 10 (-3, 23); 95%LOA: -55, 74). The ActiGraph (+LFE) achieved closest agreement to the GSSC for the stairs test (mean bias (95%CI): 0 (-1, 1); 95%LOA: -5, 5). The ActiGraph (-LFE) performed poorly in both tests. All devices demonstrated reduced accuracy in participants with lower gait velocity, reduced stride length, longer double-limb support phase and greater self-reported functional impairment. CONCLUSION: Our preliminary results suggest that in controlled conditions, the Fitbit-Zip fairly accurately measures step-count during walking in people with PMR receiving treatment. However, device error was greater than data published in healthy people. The ActiGraph may not be recommended without activation of the LFE. We identified clinical and gait-related factors associated with higher levels of functional impairment that reduced device accuracy. Further work is required to evaluate the validity of the activity monitors in field conditions.


Assuntos
Acelerometria/instrumentação , Monitores de Aptidão Física/estatística & dados numéricos , Monitorização Ambulatorial/instrumentação , Polimialgia Reumática/fisiopatologia , Caminhada/fisiologia , Acelerometria/métodos , Idoso , Idoso de 80 Anos ou mais , Teste de Esforço/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Autorrelato , Gravação em Vídeo
13.
BMJ Case Rep ; 20172017 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-29122897

RESUMO

We report a patient with chronic lymphocytic leukaemia (CLL) who was treated with idelalisib, a PI3Kδ inhibitor with rituximab. After 20 weeks of treatment, the patient developed classical signs and symptoms of polymyalgia rheumatica (PMR) in association with an elevated C reactive protein of 74 mg/L. After 2 weeks of prednisolone 15 mg daily symptoms had resolved and acute phase markers normalised. To our knowledge, this is the first report of PMR developing as a complication of PI3Kδ inhibitor treatment of CLL.


Assuntos
Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Polimialgia Reumática/complicações , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Feminino , Arterite de Células Gigantes/diagnóstico , Humanos , Fosfatidilinositol 3-Quinases/uso terapêutico , Polimialgia Reumática/diagnóstico , Polimialgia Reumática/tratamento farmacológico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Purinas/administração & dosagem , Purinas/uso terapêutico , Quinazolinonas/administração & dosagem , Quinazolinonas/uso terapêutico , Recidiva , Rituximab/administração & dosagem , Rituximab/uso terapêutico , Resultado do Tratamento
14.
J Clin Rheumatol ; 23(8): 416-420, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28926469

RESUMO

OBJECTIVE: The aim of this study was to explore, from the patient's perspective, the beneficial and adverse effects (AEs) of glucocorticoids (GCs) in patients with rheumatic diseases, to be used in the development of a patient-reported outcome measure. METHODS: A cross-sectional survey, capturing benefits and AEs of GC use, was administered to 2 groups of patients: (1) those attending a tertiary rheumatology clinic with various rheumatic diseases who had used GCs within the past year and (2) patients from the Hospital for Special Surgery rheumatoid arthritis database. RESULTS: Cohort 1 had 55 GC users, and cohort 2 had 95 GC users and 29 nonusers. The majority of GC users in both cohorts reported at least 1 AE (100%, 86%). The AE prevalence per person was 50% higher in cohort 1 compared with GC users in cohort 2 (7.7 vs. 5.3; AE ratio, 1.5; 95% confidence interval, 1.3-1.7) and 2-fold greater in cohort 2 GC users compared with GC nonusers (5.3 vs. 2.6; AE ratio, 2.0; 95% confidence interval, 1.6-2.6). In both cohorts, AEs identified as "worst" by GC users included skin thinning/easy bruising, sleep disturbance, mood disturbance, and change in facial shape. Most felt GCs helped their disease "a lot" (78%/62%) and that the benefits were greater than the AEs (55%/64%). Many AEs were more frequent in GC users than in nonusers. CONCLUSIONS: Patients receiving GC therapy for rheumatic conditions report a large number of AEs and those that have the greatest life impact are often difficult for physicians to measure. These results will inform the development of a patient-reported outcome measure to capture the effects of GCs from the patient's perspective.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Glucocorticoides , Doenças Reumáticas , Adulto , Idoso , Austrália , Estudos Transversais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Masculino , Conduta do Tratamento Medicamentoso , Pessoa de Meia-Idade , Preferência do Paciente , Medidas de Resultados Relatados pelo Paciente , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/psicologia , Estados Unidos
15.
BMJ Open ; 7(8): e017073, 2017 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-28838902

RESUMO

OBJECTIVES: Clinical management of giant cell arteritis (GCA) involves balancing the risks and burdens arising from the disease with those arising from treatment, but there is little research on the nature of those burdens. We aimed to explore the impact of giant cell arteritis (GCA) and its treatment on patients' lives. METHODS: UK patients with GCA participated in semi-structured telephone interviews. Inductive thematic analysis was employed. RESULTS: 24 participants were recruited (age: 65-92 years, time since diagnosis: 2 months to >6 years). The overarching themes from analysis were: ongoing symptoms of the disease and its treatment; and 'life-changing' impacts. The overall impact of GCA on patients' lives arose from a changing combination of symptoms, side effects, adaptations to everyday life and impacts on sense of normality. Important factors contributing to loss of normality were glucocorticoid-related treatment burdens and fear about possible future loss of vision. CONCLUSIONS: The impact of GCA in patients' everyday lives can be substantial, multifaceted and ongoing despite apparent control of disease activity. The findings of this study will help doctors better understand patient priorities, legitimise patients' experiences of GCA and work with patients to set realistic treatment goals and plan adaptations to their everyday lives.


Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/fisiopatologia , Arterite de Células Gigantes/psicologia , Glucocorticoides/uso terapêutico , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Ansiedade/psicologia , Fadiga/etiologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Pesquisa Qualitativa
16.
J Rheumatol ; 44(10): 1515-1521, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28765246

RESUMO

OBJECTIVE: To inform development of a core domain set for outcome measures for clinical trials in polymyalgia rheumatica (PMR), we conducted patient consultations, a systematic review, a Delphi study, and 2 qualitative studies. METHODS: Domains identified by 70% or more of physicians and/or patients in the Delphi study were selected. The conceptual framework derived from the 2 qualitative research studies helped inform the meaning of each domain and its relationship to the others. The draft core domain set was refined by further discussion with patients and physicians who had participated in the Delphi study. At the Outcome Measures in Rheumatology (OMERACT) 2016, the domains were discussed and prioritized by 8 breakout groups. Formal voting took place at the end of the workshop and in the final plenary. RESULTS: Ninety-three percent of voters in the final plenary agreed that the inner core of domains considered mandatory for clinical trials of PMR should consist the following: laboratory markers of systemic inflammation, pain, stiffness, and physical function. Patient's global and fatigue were considered important but not mandatory (outer core). The research agenda included psychological impact, weakness, physical activity, participation, sleep, imaging, and health-related quality of life. CONCLUSION: This core domain set was considered sufficiently well-defined that the next step will be to apply the OMERACT Filter 2.0 Instrument Selection Algorithm to select candidate instruments for a subsequent "deeper dive" into the data. This will allow instruments to be mapped onto each of our core domains to derive a core outcome set for PMR.


Assuntos
Antirreumáticos/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação de Resultados (Cuidados de Saúde) , Polimialgia Reumática/tratamento farmacológico , Técnica Delfos , Humanos , Qualidade de Vida , Projetos de Pesquisa
17.
BMC Med ; 15(1): 120, 2017 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-28655311

RESUMO

BACKGROUND: Giant cell arteritis (GCA), if untreated, can lead to blindness and stroke. The study's objectives were to (1) determine a new evidence-based benchmark of the extent of diagnostic delay for GCA and (2) examine the role of GCA-specific characteristics on diagnostic delay. METHODS: Medical literature databases were searched from inception to November 2015. Articles were included if reporting a time-period of diagnostic delay between onset of GCA symptoms and diagnosis. Two reviewers assessed the quality of the final articles and extracted data from these. Random-effects meta-analysis was used to pool the mean time-period (95% confidence interval (CI)) between GCA symptom onset and diagnosis, and the delay observed for GCA-specific characteristics. Heterogeneity was assessed by I 2 and by 95% prediction interval (PI). RESULTS: Of 4128 articles initially identified, 16 provided data for meta-analysis. Mean diagnostic delay was 9.0 weeks (95% CI, 6.5 to 11.4) between symptom onset and GCA diagnosis (I 2 = 96.0%; P < 0.001; 95% PI, 0 to 19.2 weeks). Patients with a cranial presentation of GCA received a diagnosis after 7.7 (95% CI, 2.7 to 12.8) weeks (I 2 = 98.4%; P < 0.001; 95% PI, 0 to 27.6 weeks) and those with non-cranial GCA after 17.6 (95% CI, 9.7 to 25.5) weeks (I 2 = 96.6%; P < 0.001; 95% PI, 0 to 46.1 weeks). CONCLUSIONS: The mean delay from symptom onset to GCA diagnosis was 9 weeks, or longer when cranial symptoms were absent. Our research provides an evidence-based benchmark for diagnostic delay of GCA and supports the need for improved public awareness and fast-track diagnostic pathways.


Assuntos
Arterite de Células Gigantes/diagnóstico , Diagnóstico Tardio , Humanos
18.
J Rheumatol ; 44(11): 1754-1758, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28365575

RESUMO

OBJECTIVE: The need for a standardized instrument to measure the effect of glucocorticoid (GC) therapy has been well documented in the literature. The aim of the first GC Special Interest Group was to define a research agenda around the development of a patient-reported outcome measure (PROM) in this area. METHODS: The results of a background literature search and the preliminary results of a pilot survey and 2 qualitative studies were presented to facilitate the development of a research agenda. RESULTS: It was agreed that there was a need for a data-driven PROM that identified both positive and negative effects of GC therapy to be used across all inflammatory indications for systemic GC use in adults. A research agenda was developed, consisting of further qualitative work to assess the effect of GC across different groups including various indications for GC use, different age groups, different dosages, and duration of treatment. CONCLUSION: There was agreement on the need for a PROM in this area and a research agenda was set.


Assuntos
Glucocorticoides/uso terapêutico , Inflamação/tratamento farmacológico , Humanos , Medidas de Resultados Relatados pelo Paciente , Projetos Piloto , Resultado do Tratamento
19.
Am J Hum Genet ; 100(1): 64-74, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28041642

RESUMO

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analyzed in 2,134 case subjects and 9,125 unaffected individuals from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, p = 1.94 × 10-54, per-allele OR = 1.79; and rs9275592, p = 1.14 × 10-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, p = 1.23 × 10-10, OR = 1.28; and rs128738, p = 4.60 × 10-9, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis.


Assuntos
Alelos , Predisposição Genética para Doença/genética , Variação Genética , Estudo de Associação Genômica Ampla , Arterite de Células Gigantes/genética , Plasminogênio/genética , Prolil Hidroxilases/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Europa (Continente)/etnologia , Feminino , Humanos , Masculino , Neovascularização Fisiológica , Polimorfismo de Nucleotídeo Único/genética , Risco
20.
J Rheumatol ; 44(12): 1904-1910, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27980014

RESUMO

OBJECTIVE: The objectives of the Outcome Measures in Rheumatology (OMERACT) Stiffness special interest group (SIG) are to characterize stiffness as an outcome in rheumatic disease and to identify and validate a stiffness patient-reported outcome (PRO) in rheumatology. METHODS: At OMERACT 2016, international groups presented and discussed results of several concurrent research projects on stiffness: a literature review of rheumatoid arthritis (RA) stiffness PRO measures, a qualitative investigation into the RA and polymyalgia rheumatica patient perspective of stiffness, data-driven stiffness conceptual model development, development and testing of an RA stiffness PRO measure, and a quantitative work testing stiffness items in patients with RA and psoriatic arthritis. RESULTS: The literature review identified 52 individual stiffness PRO measures assessing morning or early morning stiffness severity/intensity or duration. Items were heterogeneous, had little or inconsistent psychometric property evidence, and did not appear to have been developed according to the PRO development guidelines. A poor match between current stiffness PRO and the conceptual model identifying the RA patient experience of stiffness was identified, highlighting a major flaw in PRO selection according to the OMERACT filter 2.0. CONCLUSION: Discussions within the Stiffness SIG highlighted the importance of further research on stiffness and defined a research agenda.


Assuntos
Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Inflamação/diagnóstico , Doenças Musculoesqueléticas/diagnóstico , Polimialgia Reumática/diagnóstico , Artrite Psoriásica/fisiopatologia , Artrite Reumatoide/fisiopatologia , Progressão da Doença , Humanos , Inflamação/fisiopatologia , Doenças Musculoesqueléticas/fisiopatologia , Polimialgia Reumática/fisiopatologia , Reumatologia , Índice de Gravidade de Doença , Avaliação de Sintomas
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