109 research outputs found
The Role of Ultrasound Across the Inflammatory Arthritis Continuum: Focus on âAt-Riskâ Individuals
In individuals at-risk of developing inflammatory arthritis, the value of an ultrasound (US) scan assessment to predict progression has been demonstrated repeatedly. However, depending on recruitment criteria, these individuals may be at different stages in the arthritis development continuum, therefore representing a heterogeneous population. As a consequence, the predictive value of ultrasound results may differ between cohorts. As other reviews have focused on the challenges in population recruitment or have combined biomarkers predicting value according to one recruitment pathway, we wanted to focus on the sole use of ultrasound assessment and its variation according to population recruitment criteria. In this review, we discuss the use of ultrasound in the different at-risk populations across the inflammatory arthritis disease continuum. This review demonstrates that although some sub-population data is scarce, ultrasound is best predictive in three at-risk populations: those with a positive ACPA test in the context of non-specific MSK symptoms, those with clinically suspect arthralgia and those with palindromic rheumatism. We consider that ultrasound assessment will be a cornerstone in prediction risk modeling and prevention studies of the preclinical phases of IA in the future
Predicting Successful Tapering of Biologic Therapy for Patients with Rheumatoid Arthritis in Remission â Why are we still using clinical remission criteria to inform decisions?
Remission is the optimum treatment target for patients with rheumatoid arthritis. With the advent of biologic therapies, and the use of treat to target strategies, many more patients are achieving remission. Once a patient has achieved a period of sustained remission, there is little to guide subsequent management and patients usually continue treatment long-term. This may be inappropriate. Recent evidence suggests that some patients may be able to reduce or even stop therapy however, the ideal patient profile is yet to be determined. Potential predictors have been identified, however have not entered routine clinical practice. There is a need for robust biomarkers to facilitate the prediction of successful tapering
Ultrasound erosions in the feet best predict progression to inflammatory arthritis in anti-CCP positive at-risk individuals without clinical synovitis
Objectives To investigate, in anti-cyclic citrullinated peptide antibody positive (CCP+) at-risk individuals without clinical synovitis, the prevalence and distribution of ultrasound (US) bone erosions (BE), their correlation with subclinical synovitis and their association with the development of inflammatory arthritis (IA).
Methods Baseline US scans of 419 CCP+ at-risk individuals were analysed. BE were evaluated in the classical sites for rheumatoid arthritis damage: the second and fifth metacarpophalangeal (MCP2 and MCP5) joints, and the fifth metatarsophalangeal (MTP5) joints. US synovitis was defined as synovial hypertrophy (SH) â„2 or SH â„1+power Doppler signal â„1. Subjects with â„1 follow-up visit were included in the progression analysis (n=400).
Results BE were found in â„1 joint in 41/419 subjects (9.8%), and in 55/2514 joints (2.2%). The prevalence of BE was significantly higher in the MTP5 joints than in the MCP joints (p1 joint 10.6 (95% CI 1.9 to 60.4, p<0.01) and BE and synovitis in â„1 MTP5 joint 5.1 (95% CI 1.4 to 18.9, p=0.02). In high titre CCP+ at-risk individuals, with positive rheumatoid factor and BE in â„1 joint, the OR increased to 16.9 (95% CI 2.1â132.8, p<0.01).
Conclusions In CCP+ at-risk individuals, BE in the feet appear to precede the onset of clinical synovitis. BE in >1 joint, and BE in combination with US synovitis in the MTP5 joints, are the most predictive for the development of clinical arthritis
Redundancy, Deduction Schemes, and Minimum-Size Bases for Association Rules
Association rules are among the most widely employed data analysis methods in
the field of Data Mining. An association rule is a form of partial implication
between two sets of binary variables. In the most common approach, association
rules are parameterized by a lower bound on their confidence, which is the
empirical conditional probability of their consequent given the antecedent,
and/or by some other parameter bounds such as "support" or deviation from
independence. We study here notions of redundancy among association rules from
a fundamental perspective. We see each transaction in a dataset as an
interpretation (or model) in the propositional logic sense, and consider
existing notions of redundancy, that is, of logical entailment, among
association rules, of the form "any dataset in which this first rule holds must
obey also that second rule, therefore the second is redundant". We discuss
several existing alternative definitions of redundancy between association
rules and provide new characterizations and relationships among them. We show
that the main alternatives we discuss correspond actually to just two variants,
which differ in the treatment of full-confidence implications. For each of
these two notions of redundancy, we provide a sound and complete deduction
calculus, and we show how to construct complete bases (that is,
axiomatizations) of absolutely minimum size in terms of the number of rules. We
explore finally an approach to redundancy with respect to several association
rules, and fully characterize its simplest case of two partial premises.Comment: LMCS accepted pape
Comparison of remove-compute-restore and least squares modification of Stokes' formula techniques to quasi-geoid determination over the Auvergne test area
Prioritising referrals of individuals at-risk of RA: guidance based on results of a 10-year national primary care observational study
Background
Musculoskeletal (MSK) symptoms are among the commonest reasons for primary care assessments; however, few individuals will be diagnosed with an inflammatory arthritis (IA) within the following year. The purpose of this study was to investigate, in individuals with new MSK symptoms, the association between patient factors and risk of progression to IA, in order to optimise primary care referrals to rheumatology.
Methods
Individuals â„16âyears old with new non-specific MSK symptoms and no clinical synovitis were recruited by primary care across the UK from July 2007 until May 2019. Those testing positive for the anti-CCP2 assay (anti-CCP+) were invited to Leeds for follow-up. Subjects with a negative result (anti-CCPâ) were sent a 1-year questionnaire, and general practitioners were contacted to confirm whether the individual had been diagnosed with an IA by a rheumatologist. Predictors for progression were assessed using multivariable regression analysis.
Results
Six thousand seven hundred eighty individuals were recruited: 3% were anti-CCP+, of whom 45% progressed to IA, predominantly rheumatoid arthritis. Anti-CCP+ participants with high antibody levels had an odds ratio (OR) for progression to IA of 9.42 [P < 0.001, 95% CI (3.13â28.30)], hand pain, OR 2.74 [P = 0.043, 95% CI (1.03â7.27)] and foot pain, OR 4.10 [P = 0.003, 95% CI (1.59â10.54)]. In low-level anti-CCP+ individuals, absence of pain in hands or feet had a negative predictive value of 96% for progression to IA.
One-year follow-up data were available for 5640 anti-CCPâ individuals, of whom 53 were diagnosed with IA (0.93%). Pain in hands, OR 2.51 [P = 0.018, 95% CI (1.17â5.39)] or knees, OR 3.03 [P = 0.003, 95% CI (1.47â6.25)] were associated with development of IA within 12âmonths.
Conclusions
This is the largest prospective primary care study of individuals at risk of IA, and the first one to prospectively investigate the outcome of MSK symptoms in a large anti-CCPâ cohort. High anti-CCP levels and pain in hands/feet indicated an increased likelihood of progression to IA. In patients with low anti-CCP level and no pain in the hands/feet, progression is unlikely. In anti-CCPâ patients, those with hand or knee pain were at increased risk of progression. This study demonstrates that routinely available tests and joint symptoms provide useful discrimination that may be used to prioritise referrals to rheumatology and avoid a delayed diagnosis.
Trial registration
NCT, NCT02012764. Registered 25 January 2007
Ultrasound subclinical synovitis in anti-CCP-positive at-risk individuals with musculoskeletal symptoms: an important and predictable stage in the rheumatoid arthritis continuum
Objectives
To investigate whether anti-CCP2-positive at-risk individuals with musculoskeletal (MSK) symptoms but without clinical synovitis (CCP2+ at-risk) develop US subclinical synovitis before inflammatory arthritis and if US subclinical synovitis can be predicted.
Methods
First, US scans of CCP2+ at-risk individuals who developed inflammatory arthritis (âprogressorsâ) were reviewed for subclinical synovitis prior to inflammatory arthritis development. Patients in whom the pre-progression US scan was negative but the scan was conducted >6 months before progression were excluded. Subsequently, regression analyses were performed to identify predictors of US synovitis in CCP2+ at-risk individuals without baseline US abnormalities who had one or more longitudinal US scan and a complete dataset.
Results
US subclinical synovitis was detected in one or more scan in 75 of 97 progressors (77.3%) {median time to inflammatory arthritis development from first evidence of US synovitis 26.5 weeks [interquartile range (IQR) 7â60]}, in whom one or more scan was available, excluding those with a negative scan >6 months from inflammatory arthritis development (n = 38). In 220 CCP2+ at-risk individuals with normal baseline US scans, who had one or more longitudinal US scan and a complete dataset, US synovitis was detected in 69/220 (31.4%) [median time to first developing US synovitis 56.4 weeks (IQR 33.0â112.0)]. In the multivariable analysis, only anti-CCP3 antibodies were predictive for the development of US synovitis [odds ratio 4.75 (95% CI 1.97, 11.46); P < 0.01].
Conclusions
In anti-CCP2+ at-risk individuals, a stage of subclinical synovitis usually precedes the development of inflammatory arthritis. Anti-CCP2+/CCP3+ individuals without clinical or US subclinical synovitis may represent the optimal window of opportunity for intervention to prevent joint disease
Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses
Objectives To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs).
Methods This prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4âweeks post-vaccination. Positive antibody response was defined as sera IgG binding to â„1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of â„7 interferon (IFN)Îł-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score.
Results After vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (p<0.001). Better seroconversion occurred with anti-tumour necrosis factor (TNF) versus RTX (p=0.012) and with age â€50 (p=0.012). Pre-vaccine SARS-CoV-2 exposure was associated with higher quantitative seroconversion (â„3 antibodies) (p<0.001). In the subgroup of non-seroconverters, a second vaccination produced seroconversion in 54% (19/35), and after a third in 20% (2/10). IFN score analysis showed no change post-vaccine.
Conclusion Patients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses
Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry
Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01â1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23â3.99] compared to eGFR â„90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF
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