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ID PMID Title PublicationDate abstract
20889362 Weekly home self-assessment of RAPID-4/3 scores in rheumatoid arthritis: a 6-month study i 2010 Dec OBJECTIVES: To investigate whether weekly determination of Routine Assessment of Patient Index Data (RAPID) scores 3 and 4 in patients with rheumatoid arthritis (RA) improved the assessment of disease activity and detected additional activity peaks (predictive of additional structural damage). METHODS: Each week for 6 months, 26 patients with RA completed the patient-reported outcome questionnaires RAPID-3 and RAPID-4. During the study period, the treatment regimen for RA remained unchanged in 23 of the 26 patients. RESULTS: RAPID-3 was as informative as RAPID-4. Mean values were 3.85±1.66 (range: 0.72-6.85) and 3.43±1.57 (range: 0.81-6.77), respectively. The areas under the RAPID-3 score curves plotted using only the first and last weeks or all the weeks showed a statistically significant difference in 19 (73%) of the 26 patients. The difference between the highest and lowest RAPID-3 scores was greater than the clinically significant threshold of 1.2 in all 26 patients (mean difference: 2.95±0.71; range: 1.6-5.5). In 13 patients, the RAPID-3 score detected one (one patient) or several (12 patients) activity peaks. Among RAPID-3 score components, the visual analog scale (VAS) pain score had the greatest influence (37% of the total score), followed by the VAS disease-activity score (36%) then by the multidimensional Health Assessment Questionnaire score (27%). Scores were not influenced by patient mood at questionnaire completion. CONCLUSION: Self-evaluation at home using the RAPID-3 score provides additional information that should improve the accuracy of RA monitoring between physician visits and that may help to optimize visit scheduling.
19369466 The uses of disease activity scoring and the physician global assessment of disease activi 2009 May OBJECTIVE: To evaluate the uses of quantitative disease activity scoring and a physician global assessment of disease activity for managing rheumatoid arthritis (RA) in rheumatology practice. METHODS: The Global Arthritis Score (GAS) and a physician global assessment (Physician Global) were determined during each office visit for a community practice RA population. The GAS was calculated from patients' self-reported pain, functional assessment, and tender joint count. The Physician Global was recorded on a 10-point visual analog scale. The correlation of these 2 disease activity measures was determined for the most recent office visit of 185 patients with RA, and the reasons for discordant results were identified by chart review. RESULTS: The GAS and Physician Global were concordant for active or inactive disease in 126 of 185 patients (68%) and were discordant in 59 (32%). Forty-five of these discordant patients had a high GAS while their Physician Global indicated inactive disease. Their GAS values were high because of osteoarthritis, back pain, soft tissue rheumatism, and/or prior joint damage rather than active RA. The other 14 patients had a low GAS with an uncontrolled Physician Global for a variety of reasons. CONCLUSION: (1) An RA disease activity score and a quantitative Physician Global can be measured during rheumatology office visits to document patients' disease status. (2) Disease activity scoring contributes valuable information, but should not replace the Physician Global in guiding RA patient management or reimbursement decisions.
19604439 The use of computer touch-screen technology for the collection of patient-reported outcome 2009 May OBJECTIVES: To investigate the acceptability, feasibility, reliability and score agreement of collecting rheumatoid arthritis (RA) patient-reported outcome (PRO) data using an interactive touch-screen computer system. METHODS: Eighty-seven RA patients completed both the touch-screen and conventional paper-administered set of questionnaires. For this purpose, we have developed a computerized touch-screen system, namely RHEUMATISM (RHEUMA Touch-screen Italian SysteM), to capture PRO data. Variables recorded include the following information: demographic data, VAS scores for pain, patient's and physician's assessment of global activity, and physician's assessment of general health status, 28-joint counts measuring tender and swollen joint, patient self-reported tender joint count, Recent-Onset Arthritis Disability index, and laboratory findings. In a further test-retest study, 35 patients were evaluated. RESULTS: Although over half the patients had no prior computer experience, nearly all found the touch-screen easy to use. Moreover, 86% of the patients preferred the computer format to the paper format (2%) and 12% of subjects had no preference. The quality of the data collected with the touch-screen system was good, with no missed responses. Agreement between scores obtained with the two modes of administration was very good, with concordance correlation coefficients (CCCs) from 0.887 to 0.972. CCCs were similar in men and in women, in subjects with or without prior computer experience and in subjects below or above age 65. The electronic questionnaire had good test-retest reliability (CCCs from 0.836 to 0.907). CONCLUSIONS: Computer touch-screen questionnaires were well accepted by RA patients, with good data quality, reliability and score agreement.
20360184 Reproducibility of joint swelling assessments in long-lasting rheumatoid arthritis: influe 2010 May OBJECTIVES: To evaluate the reproducibility of clinical synovitis assessments in rheumatoid arthritis and the effect of variability on the Disease Activity Score-28 (DAS28). METHODS: Seven healthcare professionals from different cities examined the same patients with active non-early rheumatoid arthritis (RA; duration > 4 yrs), for whom a treatment change was being considered. There was no training session and the examination was to be performed as quickly as possible. The healthcare professionals assessed the 28 joints of the DAS28 in 7 patients (196 joints), then reexamined the same 28 joints in 4 of these 7 patients (112 joints), who had been rendered unrecognizable. Then 7 sonographers examined each of the 7 patients twice, using B-mode and power Doppler ultrasound (PD). The reference standards were presence of synovitis according to at least 50% of clinical examiners and 50% of sonographers. Agreement was assessed by Cohen's kappa statistic. RESULTS: Intraobserver reliability ranged from 0.31 (least experienced research technician) to 0.77 (most experienced physician). Interobserver reliability ranged from 0.18 to 0.62. The largest difference between the lowest and the highest swollen joint counts in the same patient was 15, and the greatest variation in the DAS28 score was 0.92. Agreement between clinical and sonographic reference standards was 0.46, 0.37, and 0.36 for B-mode, PD, and both, respectively. CONCLUSION: Clinical inter- and intraobserver reliability is highly dependent on the examiner. Consequences on the DAS28 score can be substantial. Agreement with sonography is poor when both B-mode and PD are used but seems better, although low, when B-mode is used alone.
19841842 Factors related to fatigue in women and men with early rheumatoid arthritis: the Swedish T 2009 Nov OBJECTIVE: To study whether there are differences between women and men with regard to the reported level of fatigue, to explore the strength of the relations between fatigue and disease activity, pain, sleep disturbance, mental health, and activity limitation in early rheumatoid arthritis, and to explore the consistency of such findings. DESIGN: Analyses and comparisons of cross-sectional data. SUBJECTS: Two hundred and seventy-six patients, 191 women and 85 men, with early rheumatoid arthritis were included. METHODS: Patients were examined with respect to 28-joint count disease activity score, and disability variables reflecting pain, sleep disturbance, fatigue, mental health, and activity limitation, at follow-ups at 1, 2 and 3 years after diagnosis. RESULTS: Women reported somewhat more fatigue than men. Fatigue was closely and rather consistently related to disease activity, pain and activity limitation, and also to mental health and sleep disturbance. CONCLUSION: Although this study does not permit conclusions to be drawn about causal directions, statistical relationships may be related to clinical conceptions about causation: when disease activity can be significantly reduced by pharmacological treatment this may have a positive effect on fatigue. Specific treatment with respect to the mentioned disability aspects that are related to fatigue is also a clinically reasonable strategy.
19822045 A systematic comparison of rheumatoid arthritis and ankylosing spondylitis. 2009 Jul The clinical manifestations of rheumatoid arthritis (RA) and ankylosing spondylitis (AS) differ in many ways. The age of onset in AS is much younger, with an average onset of 28 years compared with 40-50 years in RA, and with a male predominance (3:1) compared with the female predominance in RA. The genetic association with HLA alleles is stronger in AS, with an HLA-B27 antigen in 95% of the patients compared with RA, with 60% HLA DR4 or DR 1 positives. The type and localisation of arthritis is peripheral polyarthritis in RA, especially with involvement of hands and feet, whereas in AS the arthritis is mainly localized in the spine and sacroiliac joints with an oligoarthritis of the larger joints (hips, knees, shoulders). The radiographic signs in RA show bone resorption with erosive changes in contrast with AS where bone formation with vertebral sydesmophytes is present. Extra-articular manifestations can occur in both diseases but again these manifestations differ in the eye (keratoconjuctivitis sicca and scleritis in RA, versus anterior uveitis in AS), heart (pericarditis in RA, conduction disturbances in AS), lungs (pleural lesions or nodules in RA and fibrosis in AS) and gastrointestinal tract (peptic ulcers in RA and colitis in AS).Both diseases respond well to treatment with NSAIDs but DMARDs, which are very important in RA, have limited value in AS. TNF alfa blocking drugs, however, show a high efficacy in both diseases.
19955223 The Michael Mason prize: early rheumatoid arthritis--the window narrows. 2010 Mar RA is a chronic disease in which synovitis drives joint destruction. Immunomodulatory therapy in the established phase of disease limits synovitis, and slows the rate of joint destruction, but is not curative. Increasing evidence suggests that the very early phase of RA, within the first few months after the onset of symptoms, represents a pathologically distinct and temporally transient window during which outcomes can be more effectively modulated by therapy. Furthermore, recent data show that we can accurately predict the development of RA in patients with very early synovitis, using clinical and serological measures. This makes very early targeted treatment a realistic possibility. However, it remains the case that the majority of patients with very early synovitis delay for prolonged periods before seeking medical help. Effective public engagement, to reduce this delay, is the key to translate advances in the fields of pathology, prognostication and therapy into benefit for patients with new onset RA.
19918048 Increased levels of interleukin 33 in sera and synovial fluid from patients with active rh 2010 Jan OBJECTIVE: To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33. METHODS: Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1beta and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting. RESULTS: Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS. CONCLUSION: IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA.
19096748 Underweight and obese states both associate with worse disease activity and physical funct 2009 Apr Obesity is characterised by low-grade inflammation and could potentially affect disease activity and severity in patients with rheumatoid arthritis (RA). Body mass index (BMI), body fat (BF), erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, physical function (health assessment questionnaire) and presence of erosions and joint surgery were assessed in 294 (female=219) volunteers with established RA [age 63.3 (56.2-69.6); disease duration 13 (7-20) years]. Smoking status, rheumatoid factor and anti-cyclic citrullinated peptide positivity were also assessed. BMI and BF independently associated with disease characteristics. Compared to normal-weight patients, underweight and obese had higher C-reactive protein (p=0.046) and physical dysfunction (p=0.034). BMI or BF did not associate with presence of erosions or joint surgery. In patients with established RA, both very low and very high BMI and BF associate independently with increased disease activity and physical dysfunction; however, this does not seem to associate with presence of erosions or joint surgery. Further longitudinal studies are required to address this apparent dissociation.
19604434 A mismatch between self-reported physical work load and the HAQ: early identification of r 2009 May OBJECTIVE: To explore the combination of data on functioning and work load for early identification of patients at risk for diminished work productivity in rheumatoid arthritis (RA). PATIENTS AND METHODS: In the FIN-RACo trial, 162 patients with recent onset RA and available for the workforce were treated with either a combination of disease-modifying antirheumatic drugs (DMARDs) or a single DMARD for 2 years. Otherwise, they received routine care and were followed up for 5 years. Data on their individual income and lost work days came from official registers. Loss of productivity was computed by the human capital approach. Self-reported data on physical work demand (Finnish Institute for Occupational Health Questionnaire) at baseline and on functioning (HAQ) at 6 months were linked according to the International Classification of Functioning, Disability and Health. RESULTS: Data on 112 patients were analyzable at 6 months; 35 (31%) of them had diminished capacity in functions required at paid work. Any mismatch between perceived abilities and requirements predicted future (7 through 60 months) loss of productivity - on average Euro 14,040 (95% confidence interval (CI): 9,143-20,511) per year in patients with the mismatch compared to Euro 3,043 (1,623-5,534) in those without any mismatch - and was associated with RA-related permanent work disability (hazard ratio: 11.6; 95%CI: 4.0-33.4). CONCLUSION: Linking together self-reported data about functioning and work load helps in early identification of the RA patients at risk for loss of working days.
19333678 Associations between methotrexate treatment and methylenetetrahydrofolate reductase gene p 2009 Several case reports have described associations between pathological nonvertebral fractures and low-dose methotrexate (MTX) in rheumatoid arthritis (RA) patients. Furthermore, a significant association between the C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene and incident fractures has been reported in postmenopausal women. We attempted to determine whether MTX use and MTHFR polymorphisms are associated with incident fracture risk in Japanese female RA patients. DNA samples, laboratory data, and clinical data were obtained from 731 female RA patients more than 50 years old as part of the Institute of Rheumatology Rheumatoid Arthritis (IORRA) observational cohort study. Genotyping of the MTHFR polymorphisms C677T and A1298C was performed using TaqMan SNP Genotyping Assays. MTX use, MTHFR polymorphisms, and other potential risk factors predictive of fracture were analyzed by Cox proportional hazards regression models, including time-dependent covariates. During 78 months from October 2000 to March 2007, 25 and 90 patients developed vertebral and nonvertebral fractures, respectively. Patients with nonvertebral fractures were more likely to take MTX (P = 0.011; odds ratio, 1.77; 95% confidence interval, 1.13-2.76) compared to patients without fractures. Although the C677T and A1298C polymorphisms were not significantly associated with incident fracture risk, MTX use, age, disease duration, and Japanese health assessment questionnaire score were significantly (P < 0.05) and independently associated with nonvertebral fracture incidence. Our results suggest that MTX use is associated with a nonvertebral fracture risk, whereas MTHFR polymorphism status does not appear to be a clinically useful marker for predicting fracture risk in Japanese female RA patients.
21125174 Laboratory characteristics of a cohort of patients with early rheumatoid arthritis. 2010 Jul INTRODUCTION/OBJECTIVE: To characterize a population of patients with early rheumatoid arthritis (RA) according to laboratory aspects, comparing it with other similar cohorts. METHODS: Data presented are part of a prospective incident cohort study that evaluated 65 patients with early RA, followed for 36 months from the diagnosis at Early Rheumatoid Arthritis Clinic of Hospital Universitário de Brasília (HUB). We recorded demographics, clinical, and laboratory data relevant to the cohort initial assessment, including red blood cells, evidence of inflammatory activity, and presence of autoantibodies (rheumatoid factor (RF)), cyclic citrullinated peptide antibodies (anti-CCP), and antivimentin citrullinated (anti-Sa). RESULTS: There was a preponderance of female (86%) with mean age of 45.6 years. Twelve patients (18.46%) had laboratory diagnosis of anemia (hemoglobin < 12 g / dL). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were above the reference value for 51 (78.46%) and 46 (70.76%) patients, respectively. Thirty-two patients (49.23%) were positive for at least one of the RF isotypes, and 28 patients (43.07%) were positive for IgA RF, 19 (29.23%) for IgG, and 32 ( 49.23%) for IgM RF, respectively; 34 patients (52.30%) were positive for at least one of the techniques used in investigation of anti-CCP (CCP2, or CCP3, or CCP3.1), while 9 (13,85%) were positive for anti-Sa. CONCLUSIONS: The laboratory characteristics of patients enrolled in this Brazilian cohort are similar in many respects to those of North-American, European, and Latin-American cohorts previously published.
20889597 Disease progression and treatment responses in a prospective DMARD-naive seropositive earl 2010 Dec OBJECTIVE: To assess gender differences in disease characteristics and treatment responses over time in a disease-modifying antirheumatic drug (DMARD)-naive seropositive early rheumatoid arthritis (RA) cohort. METHODS: Patients with polyarticular disease who were DMARD-naive and had seropositive early RA (< 14 months) were recruited by the Western Consortium of Practicing Rheumatologists. Each patient was examined at study entry, after 6 and 12 months, and yearly thereafter. Clinical and demographic data were collected. We investigated gender differences in baseline disease characteristics and treatment using chi-squared, Mann-Whitney U, and t tests. We used generalized estimating equations (GEE) models for repeated measures to examine whether the rate of change of specific disease outcomes during the first 2 years after DMARD initiation was significantly influenced by gender. RESULTS: At baseline, men (n = 67) and women (n = 225) had similar disease activity and radiographic damage; men, however, had significantly worse erosion, while women had worse joint space narrowing. Despite similar treatment, women had worse disease progression over the 2-year followup, as assessed by trends in Disease Activity Score 28/erythrocyte sedimentation rate (DAS28-ESR4), physician global scores, and tender joint counts. In the GEE model, gender was significantly associated with the rate of change of DAS28-ESR4 scores (p = 0.009), although not independently associated with disease activity. Self-reported measures (Health Assessment Questionnaire-Disability Index, patient global scores, fatigue, pain) were worse among women at baseline and throughout the study period. Men were more likely to achieve remission. CONCLUSION: At baseline, men and women had similar disease activity and joint damage. Responses to treatment over time were better among men in this prebiologic era; women had worse progression despite similar treatment.
20403067 Disease-modifying anti-rheumatic drug usage, prescribing patterns and disease activity in 2011 Jun AIMS: Our aim was to examine the spectrum of disease activity and usage of disease-modifying anti-rheumatic drugs (DMARD) in rheumatoid arthritis (RA) patients seen over a period of 12 months in community-based rheumatology practice. METHODS: Data were prospectively collected on 1059 consecutive RA patients who attended two private, community-based rheumatology clinics from 1 May 2007 to 1 May 2008. Information on patient demographics, medication history and disease activity was collected. Life table graphs were developed to track medication retention over time. Statistical significance was determined by log-rank tests. RESULTS: One thousand and fifty-nine patients with RA were entered into the database over a 12-month period. Eight hundred and twenty-six patients (85%) were treated with single or combination conventional DMARD compared with 159 patients (15%) on a biologic DMARD either alone or in combination. Methotrexate monotherapy was the most commonly prescribed DMARD, used in 41% of patients studied. Almost half (47%) were on combination DMARD therapy. Methotrexate and tumour necrosis factor inhibitors had the highest retention rate over 12 and 30 months since first prescription. A large proportion of patients (47%) had moderate disease activity. CONCLUSION: Rates of biologic DMARD usage were similar to other studies and the predominance of methotrexate use was also in keeping with current recommendations for management of RA. There appears to be a significant unmet need for improved disease control among RA patients with moderate disease activity, which requires further investigation.
20455827 Association between tendency towards depression and severity of rheumatoid arthritis from 2010 Jul OBJECTIVES: The association between RA and depression has been well documented but so far there is not much research at a national level and none using a quick classification system of RA. The purpose of this study is to further determine if this association varies by differing severity in functional status of RA patients. METHODS: This study involved a retrospective pooled cross-sectional analysis of the Household Component of Medical Expenditure Panel Survey (MEPS) for the years 2004-2006. Each year's medical conditions file was merged with the person-level consolidated file. A total of 289 individuals comprised the final adult sample of RA and related diseases. RA cases were classified into four classes of functional status according to the ACR classification criteria. Tendency towards depression was ascertained by Patient Health Questionnaire (PHQ-2) scores with scores greater than or equal to three classified as high tendency towards depression. Multivariate logistic regression with survey weights was done using SAS 9.1. RESULTS: After controlling for other relevant factors, patients belonging to Class III RA were 5.92 times more likely and those belonging to Class II RA were 3.78 times more likely to have high tendency towards depression as compared to Class I RA patients. Older age groups (>or=68 years) and physical activity were other significant predictors but in a negative direction, whereas a co-morbidity index of two showed a significant positive association. CONCLUSION: The study provides important evidence that in a nationally representative sample of US non-institutionalized civilians, there is a strong association of depression to RA and related diseases by functional severity. However, the findings should be interpreted with caution because the data does not offer any information on duration in relation to PHQ-2 scores, thus making it hard to deduce if tendency towards depression was present before the diagnosis of RA. Furthermore, disease-specific and data-specific validation of the Charlson comorbidity index has not been done which leaves the possibility of residual confounding.
20534319 Brain stem compression and atlantoaxial instability secondary to chronic rheumatoid arthri 2010 May OBJECTIVE: This case study describes a patient with long-standing rheumatoid arthritis of the cervical spine who presented with significant bone destruction, gross joint derangement, and a potentially life-threatening complication, basilar invagination with brain stem compression. The pathophysiology, clinical presentation, imaging, and surgical management are discussed. CLINICAL FEATURES: A 67-year-old female presented to a chiropractic clinic with chronic neck pain of 30 years of duration complicated by rheumatoid arthritis. Her neck pain had recently exacerbated and was radiating into her trapezius muscle and shoulders. She also reported a recent onset of mild dysphagia. The patient was referred to a neurosurgeon for consultation and management. INTERVENTION AND OUTCOME: Computed tomography and magnetic resonance imaging of the cervical spine demonstrated significant bone destruction, gross joint derangement, and basilar invagination. There was moderate stenosis of the foramen magnum secondary to basilar invagination with significant brain stem compression. The patient underwent surgical stabilization fusion from the occiput to T2 using a posterior approach. Her pain severity was lessened after surgery, and the dysphagia had not progressed suggesting stabilization of brain stem compression. CONCLUSION: Patients with long-standing rheumatoid arthritis of the cervical spine often present with chronic neck pain. Cervical spine instability may arise from rheumatoid osteolysis and is also secondary to horizontal or vertical subluxation of the atlantoaxial and occipitoatlantal regions, respectively. High-velocity, low-amplitude manipulation of the upper cervical spine is an absolute contraindication in cases of atlantoaxial instability. A timely diagnosis and favorable surgical outcome provided relief from a potentially life-threatening disorder. This case exemplifies the clinical caution necessary for managing patients with chronic cervical spine pain complicated by rheumatoid arthritis.
19139203 Does damage cause inflammation? Revisiting the link between joint damage and inflammation. 2009 Feb Rheumatoid arthritis (RA) is characterised by both inflammation, as manifested by pain and swelling, and destruction of the joints. Unequivocal evidence indicates that disease activity, and thus the inflammatory response, is linked to joint damage. From this viewpoint we suggest that, vice versa, joint damage might be a cause of the active disease process, thus leading to a vicious cycle of events. The background to this notion stems from the known autoimmune response in RA, the potential of cartilage and bone breakdown products to elicit inflammation and notions that in joints that have undergone surgery with cartilage removal RA does not flare. However, the clinical evidence for this relationship is still to be provided as proof of the concept.
20877716 A genetic association study of serum acute-phase C-reactive protein levels in rheumatoid a 2010 Sep 21 BACKGROUND: The acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation. METHODS AND FINDINGS: We studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p = 0.002, p<0.0005, p<0.0005 in patient sets 1, 2, and the combined sets, respectively), translating into an approximately 3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example, when ESR = 50 mm/h the expected geometric mean CRP (95% confidence interval) concentration was 43.1 mg/l (32.1-50.0) for haplotype 1 and 14.2 mg/l (9.5-23.2) for haplotype 4. CONCLUSIONS: Our findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP-associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement.
20191528 Responsiveness of self-report and therapist-rated upper extremity structural impairment an 2010 Feb OBJECTIVE: To provide a responsiveness analysis of the self-report and therapist-rated upper extremity functional outcome measures used in a rehabilitation trial. METHODS: A variety of commonly used therapist-assessed and self-report structural impairment and functional outcome measures were compared for the ability to detect and measure change in wrist and hand status in an early rheumatoid arthritis population over 12 months. Responsiveness was measured using the standardized response mean (SRM) and effect size (ES). RESULTS: The most responsive measures were the Michigan Hand Outcomes Questionnaire (SRM 0.49 [95% confidence interval (95% CI) 0.27, 0.72], ES = 0.37 [95% CI 0.21, 0.54]), dominant metacarpophalangeal joint ulnar deviation (SRM 0.46 [95% CI 0.27, 0.65], ES = 0.58 [95% CI 0.34, 0.82]), and mean power handgrip test (SRM 0.45 [95% CI 0.26, 0.64], ES = 0.32 [95% CI 0.18, 0.45]) The least responsive measure was the Health Assessment Questionnaire (SRM -0.12 [95% CI -0.31, 0.08], ES = -0.08 [95% CI -0.21, 0.05]). CONCLUSION: Over 12 months, there was substantial variation in wrist and hand outcome measures to detect change over time in an early RA population. Careful consideration is required to choose the most appropriate measure that can detect change.
19159118 On the origins of complex immune-mediated disease: the example of rheumatoid arthritis. 2009 Apr This essay discusses strategies for understanding the origins and outcomes of complex chronic inflammatory diseases using genetic and environmental determinants as tools for new definitions of disease subsets. Rheumatoid arthritis has been chosen as the prototype to illustrate these general concepts. Through recent data on two different disease subsets, it has been possible to devise a new molecular model for disease development by incorporating multiple genes and environmental agents which generate immune reactions that may eventually cause disease. These kinds of studies, aiming to integrate genetic epidemiology and molecular immunology, require close proximity between institutions for molecular medicine, clinical departments able to provide follow-up, careful surveillance of large patient groups and collaboration with experts in epidemiology and biostatistics.