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Biomedical subjects

Alan J Silman

Publications and source records attributed to Alan J Silman.

At least 19 recordsLinked to original sources
PubMed2007

HLA-Cw6 and HLA-DRB1*07 together are associated with less severe joint disease in psoriatic arthritis.

BACKGROUND: Human leucocyte antigen (HLA) genes predict disease severity in psoriasis (HLA-Cw6) and rheumatoid arthritis (shared epitope (SE)), but the situation is unclear for psoriatic arthritis (PsA). AIM: To determine the association of the HLA-Cw6 and HLA-DRB1 gene with disease severity in a large UK cohort with PsA. METHODS: Genotyping of the HLA-Cw and HLA-DRB1 loci was undertaken in DNA samples from patients with PsA (n = 480). Stratification and regression analysis were used within the PsA cases to determine whether HLA-Cw6, HLA-DRB1 or the presence of the SE alleles predicted disease severity as measured by the Health Assessment Questionnaire score, the total number of damaged or involved joints adjusted for disease duration and disease-modifying antirheumatic treatments. RESULTS: HLA-Cw6 was found to be in linkage disequilibrium with HLA-DRB1*07 (r(2) = 0.46). Patients with PsA who carried both HLA-Cw6 and HLA-DRB1*07 had fewer damaged or involved joints (41% fewer damaged (95% CI 23% to 55%, p = 0.02) and 31% fewer involved joints (95% CI 16% to 44%, p<0.001)) compared with those who carried neither HLA-Cw6 nor HLA-DRB1*07 alleles. Those who carried either HLA-Cw6 or HLA-DRB1*07 alleles alone had no evidence of a reduction in joint involvement. The SE, HLA-DRB1*03 and HLA-DRB1*04 alleles did not predict severity using these outcome measures. CONCLUSION: Patients with PsA carrying both HLA-Cw6 and HLA-DRB1*07 alleles have a less severe course of arthritis. This suggests that a protective locus lies on a haplotype marked by these alleles. No association was detected with disease severity and SE status.

Adolescent↗
PubMed2007

Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) who experience treatment failure with one anti-tumor necrosis factor (anti-TNF) agent, due to either inefficacy or toxicity, are frequently switched to a second anti-TNF agent, although the benefits of switching are unknown. The present study was undertaken to compare drug continuation rates between the first course and second course of anti-TNF therapy. METHODS: The study involved a prospective cohort of RA patients from a UK national register of new anti-TNF treatment starts (n = 6,739; 876 starting adalimumab, 2,826 starting etanercept, and starting 3,037 infliximab). Over a mean 15 months of followup, 841 patients stopped taking the first drug due to inefficacy and 1,023 stopped the first drug due to toxicity, of whom 503 and 353, respectively, were switched to a second anti-TNF agent. Kaplan-Meier survival curves were plotted to determine continuation rates for each course, and Cox regression was used to compare each course for the risk of stopping and the reason for stopping (inefficacy or toxicity). RESULTS: Overall, 73% of patients who switched to a second anti-TNF agent remained on the new therapy by the end of followup. First drug discontinuation due to inefficacy was associated with an increased rate of second drug discontinuation due to inefficacy (hazard ratio [HR] 2.7, 95% confidence interval [95% CI] 2.1-3.4) but not toxicity (HR 1.1, 95% CI 0.9-1.5). Similarly, first drug discontinuation due to toxicity was associated with an increased rate of second drug discontinuation due to toxicity (HR 2.3, 95% CI 1.9-2.9) but not inefficacy (HR 1.2, 95% CI 0.8-1.6). CONCLUSION: RA patients who are switched to a second anti-TNF drug have high rates of continuation, although among those who must discontinue treatment, the reasons for stopping a second drug are related to the reasons for stopping the first drug. This large data set from the UK provides the first estimates of the magnitude of these effects in patients with long-standing severe RA.

Actuarial Analysis↗
PubMed2006

Early functional disability predicts both all-cause and cardiovascular mortality in people with inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE: To investigate the predictive value of early functional disability in patients with inflammatory polyarthritis (IP), for all-cause and cardiovascular disease (CVD) mortality. METHODS: 1010 subjects with new-onset IP from the Norfolk Arthritis Register were studied. All were seen at baseline and at 1 year. Health Assessment Questionnaire (HAQ) scores were obtained at both time points. Vital status at 10 years from registration was established through central records. Mortality (all-cause and CVD) per 1000 person-years were calculated by HAQ stratum (HAQ scores<1, 1-2 and>or=2). The predictive value of HAQ (per unit increase) at the two time points, adjusted for age at onset of symptom, sex and other factors found to predict mortality, was assessed using Cox regression models. The analysis was repeated for those who satisfied the 1987 American College of Rheumatology criteria for rheumatoid arthritis (RA) by 5 years. RESULTS: By 10 years, 171 (16.9%) subjects had died. 89 deaths (52%) were attributed to CVD. Mortality was greatest in the highest HAQ group at both time points. Following adjustment for other predictors, HAQ score at year 1 remained a significant predictor of all-cause mortality (HR 1.46; 95% CI 1.15 to 1.85) and CVD mortality (HR 1.49; 95% CI 1.12 to 1.97). The predictive value of HAQ at year 1 was similar in the RA subgroup. CONCLUSIONS: Our data show that at 1 year of follow-up, HAQ score is an important independent predictor of subsequent all-cause and CVD mortalities in people with IP and RA. Baseline HAQ scores are of less value.

Activities of Daily Living↗
PubMed2006

Lumbar disc degeneration: association between osteophytes, end-plate sclerosis and disc space narrowing.

BACKGROUND: Lumbar disc degeneration is characterised radiologically by the presence of osteophytes, end-plate sclerosis and disc space narrowing. AIM: To determine the strength of the association between increasing severity of combinations of these features in a population sample of men and women. METHODS: Men and women aged >or=50 years were recruited from a primary care-based community health index in Aberdeen, UK. Participants had lateral spinal radiographs performed according to a standard protocol. The intervertebral disc spaces (L1/2-L4/5) were evaluated for the presence of anterior osteophytes, end-plate sclerosis and disc space narrowing using a graded semiquantitative score (grade 0-3). Log linear modelling was used to determine the associations (pairwise) between increasing severity of these features, with the results expressed as beta coefficients and 95% confidence intervals (CIs). RESULTS: There were 286 men (mean age 65.3 years) and 299 women (mean age 65.2 years) with spinal radiographs, yielding a total of 2340 assessable lumbar vertebral levels. In all, 73% of vertebral levels had evidence of osteophytes, 26% of sclerosis and 37% of disc space narrowing. Increasing severity of osteophyte grade was associated with an increasing severity both of sclerosis and of disc space narrowing, whereas the severity of sclerosis was associated with the severity of narrowing. This was true at all vertebral levels. The strongest association, however, was between osteophytes and sclerosis (beta coefficient = 2.7, 95% CI 2.4 to 3.1). For sclerosis and narrowing the beta coefficient was 1.9 (95% CI 1.7 to 2.1), whereas for osteophytes and narrowing the beta coefficient was much weaker at 1.2 (95% CI 1.1 to 1.3). There was no important influence of vertebral level on any of these associations. CONCLUSION: The association between increasing severity of osteophytes and end-plate sclerosis is stronger than for other combinations of radiographic features of lumbar disc degeneration.

Aged↗
PubMed2006

Vitamin D status and bone mass in UK South Asian women.

INTRODUCTION: Low vitamin D status is prevalent among South Asians living in the UK. The relationship, however, between serum 25-hydroxyvitamin D level (25OHD), serum parathyroid level (PTH) and bone mass in this group of women is unknown. The aim of this study was to determine the association between serum PTH, 25OHD and bone mass in a population based sample of young UK South Asian women. MATERIALS AND METHODS: Names of South Asian women aged 18 to 36 years of Pakistani origin living in the Greater Manchester area were identified from primary care registers using validated computer software. Subjects were invited to attend for (i) a blood test for assessment of serum calcium (Ca), albumin, PTH and 25OHD and (ii) for bone mineral density (BMD) scanning using the following: areal BMD at the hip (femoral neck, total hip) and lumbar spine using dual X-ray absorptiometry (Hologic QDR 4500), and volumetric BMD at the distal radius using peripheral quantitative computed tomography (Norland Stratec XCT 2000). Linear regression was used to determine the association between serum 25OHD, PTH and BMD at the different sites with adjustments made for age. RESULTS: In all, 78 women (mean age 29.2 years) were included in the analysis. Mean serum Ca level was 2.42 mmol/l, 25OHD, 7.9 ng/ml and PTH, 52.8 pg/ml. The majority of women (94%) had serum 25OHD levels 15 ng/ml, though rose progressively in subjects with levels below 10 ng/ml. Serum 25OHD was positively associated with BMD at the hip and spine while PTH was negatively associated with BMD at the hip and spine. When categorized by serum 25OHD level there was an increase in BMD at the total hip and distal radial site at least up to levels of 15 ng/ml. CONCLUSIONS: Despite widespread recognition, hypovitaminosis D is still prevalent among young UK South Asian women. In these women a decrease in serum 25OHD level <or=15 ng/ml is associated with a progressive reduction in bone mass at the hip and wrist.

Adolescent↗
PubMed2006

Predicting the onset of knee pain: results from a 2-year prospective study of new workers.

OBJECTIVE: To determine the relative contribution of work-related mechanical (injury) factors and psychosocial factors to the onset of a new episode of knee pain, in a cohort of newly employed workers. METHODS: A prospective cohort study of newly employed workers from 12 diverse occupational settings in England (The New Workers Study). 859 newly employed workers, free of knee pain, were identified. Information about occupational mechanical factors (manual handling and postural activities), the occupational physical environment, and psychological and psychosocial factors was collected by self-completion questionnaires. Participants were followed up after 12 and 24 months to identify cases of knee pain onset. Generalised estimating equations were used to estimate the risk of new-onset knee pain, with respect to the exposures previously measured. RESULTS: In total, over the 2-year follow-up period, 108 cases of new-onset knee pain were observed. Mechanical load, postural factors, psychological distress and work-place psychosocial factors all influenced the risk of new-onset knee pain over the 2-year follow-up period. On multivariate analysis, two factors remained independently predictive of knee pain onset: lifting or carrying heavy weights in one hand, and the level of general psychological distress. CONCLUSION: In addition to mechanical (injury) factors, psychological factors are important risk factors for knee pain onset as shown in a population of young newly employed workers.

Adolescent↗
PubMed2006

Predicting new onset of widespread pain following a motor vehicle collision.

OBJECTIVE: To determine, in a group of persons involved in a motor vehicle collision, the contributions of pre-collision health and psychological factors, the social environment, collision-specific factors, and post-collision symptoms, to the new onset of widespread pain (WP). METHODS: A prospective cohort study of persons, registered with an insurance company, who had recently experienced a motor vehicle collision. Participants were sent a questionnaire to assess pre-collision health, collision-specific factors, post-collision health, and WP. Those reporting WP prior to the collision were excluded from followup. At 12 months, participants were sent a followup questionnaire to ascertain one-month period prevalence of (new onset) WP. RESULTS: In total 957 individuals took part in the baseline survey and were eligible for followup. Subsequently, 695 (73%) completed a questionnaire at 12 months, of whom 54 (7.8%) reported new WP. Few collision-specific factors predicted the onset of WP. In contrast, post-collision physical symptoms (rate ratio 2.5, 95% confidence interval 1.2-5.1), pre-collision health-seeking behavior (RR 3.6, 95% CI 1.6-7.9), pre-collision somatization (RR 1.7, 95% CI 0.99-2.8), and perceived initial injury severity (RR 1.7, 95% CI 0.9-3.3), in addition to older age (RR 3.3, 95% CI 1.5-7.1), were all independently predictive of new onset WP. In combination, these factors accounted for about a 20-fold difference in the risk of new onset WP. CONCLUSION: We identified 5 factors that independently predict the onset of WP following a motor vehicle collision. Early identification of this "at-risk" group may allow the targeting of preventive management in those at highest risk of developing future symptoms.

Accidents, Traffic↗
PubMed2006

Prevalence and associated factors for falls in women with established inflammatory polyarthritis.

OBJECTIVE: To determine the one-year period prevalence and factors associated with falls in a community based cohort of women with established inflammatory polyarthritis (IP). METHODS: The Norfolk Arthritis Register is a primary-care based inception cohort of subjects with IP aged 16 years and over. At the 10-year visit, subjects completed the Health Assessment Questionnaire (HAQ) and were examined for both active and inactive joint involvement. A subset of subjects was invited to complete a questionnaire about falls in the previous 12 months and questions about putative risk factors for falls. Logistic regression was used to determine whether there was any association between falls in the previous year and both putative disease and non-disease related risk factors. RESULTS: Of the 316 women (mean age 59 yrs) who completed the falls questionnaire, 34% reported a fall in the previous year. Falls were more frequent in those over age 75 years, although there was no significant linear increase in risk with age. Swollen joint count [per 10 joints, odds ratio (OR) 1.7; 95% confidence interval (CI) 1.0, 2.8] and increasing visual analog scale pain score (per 10 mm, OR 1.1; 95% CI 1.0, 1.2) were associated with an increased risk of falls. Those who fell had higher overall HAQ scores (OR 1.7; 95% CI 1.3, 2.3) as well as higher scores for all of the individual domains of the HAQ (OR 1.7 to 2.2). Similarly, low levels of outdoor physical activity (OR 3.3; 95% CI 1.7, 6.5), impaired vision (OR 2.7; 95% CI 1.2, 6.3), and impaired general health (OR 2.9; 95% CI 1.7, 4.8) were associated with an increased risk of falls. In a multivariate model, HAQ score, low levels of physical activity, impaired vision, and impaired general health were independently linked with falls. Sixty-one percent of subjects with 3 of these risk factors had reported a fall in the previous year. CONCLUSION: In this inception cohort of women with longstanding IP, one in 3 reported falling in the previous year. Using a simple measure, a group that had particularly high risk can be identified.

Accidental Falls↗
PubMed2006

Comparison of the response to infliximab or etanercept monotherapy with the response to cotherapy with methotrexate or another disease-modifying antirheumatic drug in patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: To compare outcome at 6 months in unselected "real-world" patients with rheumatoid arthritis treated with etanercept or infliximab as either monotherapy, cotherapy with methotrexate (MTX), or cotherapy with another disease-modifying antirheumatic drug (DMARD). METHODS: A total of 2,711 subjects starting treatment with their first biologic agent (1,453 infliximab and 1,258 etanercept) were followed up for 6 months. Outcome was assessed using the European League Against Rheumatism (EULAR) response criteria. Ordinal regression was used to model the response in the MTX and other DMARD cotherapy groups relative to the monotherapy group separately for the 2 anti-tumor necrosis factor alpha agents, after adjusting for baseline differences. RESULTS: Etanercept-treated patients had an increased likelihood of achieving a higher EULAR response category with cotherapy with MTX (odds ratio [OR] 2.0, 95% confidence interval [95% CI] 1.5-2.7) and with another DMARD (OR 1.2, 95% CI 0.9-1.6) as compared with monotherapy. For infliximab-treated patients, the likelihoods were 1.4 (95% CI 0.9-2.0) for MTX and 1.3 (95% CI 0.8-2.1) for other DMARDs versus monotherapy. Cotherapy with MTX or another DMARD produced significantly higher rates of remission with etanercept (12% and 11%, respectively) as compared with etanercept monotherapy (5%). Infliximab-treated patients showed similar remission rates in the MTX and other DMARD cotherapy groups (8% and 5%, respectively) as in the monotherapy group (7%). CONCLUSION: In this study of real-world patients, the use of MTX and, to a lesser extent, other DMARDs as cotherapy with etanercept was associated with a higher likelihood of response. Although the infliximab guidelines suggest that MTX be used as cotherapy, in clinical practice, both monotherapy and cotherapy with DMARDs other than MTX are used. These data suggest that either of the latter strategies may be useful in patients who are intolerant to MTX.

Antibodies, Monoclonal↗
PubMed2006

Genetic epidemiology of rheumatoid arthritis.

PURPOSE OF REVIEW: This review aims to summarize articles published between October 2004 and November 2005 that have investigated the genetic epidemiology of rheumatoid arthritis. RECENT FINDINGS: The consistent replication of an association between the R620W single nucleotide polymorphism in PTPN22 and rheumatoid arthritis clearly establishes this polymorphism as an important risk factor for rheumatoid arthritis. SUMMARY: Genetic investigations of rheumatoid arthritis have predominantly been single nucleotide polymorphism-based candidate gene association studies searching for markers of susceptibility, severity or treatment response. Studies of the human leukocyte antigen region have refined and added to our understanding of the complex associations to polymorphisms with this locus. PTPN22 has emerged strongly as a genuine rheumatoid arthritis susceptibility gene with replications of the association to the R620W single nucleotide polymorphism. Many investigations have been conducted on the genetics of treatment response -- some 'generic' and others specific in terms of identifying genetic influences to the mode of action and metabolism of particular agents.

Antirheumatic Agents↗
PubMed2006

In adult onset myositis, the presence of interstitial lung disease and myositis specific/associated antibodies are governed by HLA class II haplotype, rather than by myositis subtype.

The aim of this study was to investigate HLA class II associations in polymyositis (PM) and dermatomyositis (DM), and to determine how these associations influence clinical and serological differences. DNA samples were obtained from 225 UK Caucasian idiopathic inflammatory myopathy patients (PM = 117, DM = 108) and compared with 537 randomly selected UK Caucasian controls. All cases had also been assessed for the presence of related malignancy and interstitial lung disease (ILD), and a number of myositis-specific/myositis-associated antibodies (MSAs/MAAs). Subjects were genotyped for HLA-DRB1, DQA1 and DQB1. HLA-DRB1*03, DQA1*05 and DQB1*02 were associated with an increased risk for both PM and DM. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype demonstrated strong association with ILD, irrespective of myositis subtype or presence of anti-aminoacyl-transfer RNA synthetase antibodies. The HLA-DRB1*07-DQA1*02-DQB1*02 haplotype was associated with risk for anti-Mi-2 antibodies, and discriminated PM from DM (odds ratio 0.3, 95% confidence interval 0.1-0.6), even in anti-Mi-2 negative patients. Other MSA/MAAs showed specific associations with other HLA class II haplotypes, irrespective of myositis subtype. There were no genotype, haplotype or serological associations with malignancy. The HLA-DRB1*03-DQA1*05-DQB1*02 haplotype associations appear to not only govern disease susceptibility in Caucasian PM/DM patients, but also phenotypic features common to PM/DM. Though strongly associated with anti-Mi-2 antibodies, the HLA-DRB1*07-DQA1*02-DQB1*02 haplotype shows differential associations with PM/DM disease susceptibility. In conclusion, these findings support the notion that myositis patients with differing myositis serology have different immunogenetic profiles, and that these profiles may define specific myositis subtypes.

Adult↗
PubMed2006

Aspects of early arthritis. What determines the evolution of early undifferentiated arthritis and rheumatoid arthritis? An update from the Norfolk Arthritis Register.

Over 3500 patients with recent onset inflammatory polyarthritis (IP) have been recruited by the Norfolk Arthritis Register (NOAR) since 1990. Longitudinal data from this cohort have been used to examine the prevalence and predictors of remission, functional disability, radiological outcome, cardiovascular mortality and co-morbidity and the development of non-Hodgkin's lymphoma. Rheumatoid factor titre, high baseline C-reactive protein and high baseline HAQ score are all predictors of a poor outcome. There is a strong association between possession of the shared epitope and the development of erosions. Patients who satisfy the American College of Rheumatology criteria for rheumatoid arthritis (RA) have a worse prognosis than those who do not. However, it appears that these patients are a poorly defined subset of all those with IP rather than having an entirely separate disease entity. New statistical techniques offer exciting possibilities for using longitudinal datasets such as NOAR to explore the long-term effects of treatment in IP and RA.

Antirheumatic Agents↗
PubMed2005

Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents.

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress.

Adult↗
PubMed2005

Whole-genome screening for susceptibility genes in multicase families with Behçet's disease.

OBJECTIVE: Behçet's disease is generally considered to be a multifactorial disease with important genetic and environmental components. A strong association between an HLA class I antigen, HLA-B51, and Behçet's disease has long been known. However, analysis of multicase families has suggested a substantial contribution of non-HLA loci. The aim of this study was to perform a whole-genome linkage analysis for identification of other susceptibility loci for Behçet's disease in multicase families. METHODS: The study group comprised a total of 193 individuals (90 male, 103 female) from 28 multicase families of Turkish origin; 83 of the subjects (50 males, 33 females) fulfilled the International Study Group criteria for Behçet's disease. Three hundred ninety-five highly informative microsatellite markers spanning the genome were genotyped using fluorescent polymerase chain reaction primers and a fully automated electrophoresis platform. After the first analysis, 33 additional markers that were located close to the peak linkage areas were genotyped in all individuals. Nonparametric multipoint linkage analysis was carried out using GeneHunter version 2.1 software. RESULTS: Evidence for linkage (P < or = 0.05) was obtained in 16 chromosome regions: 1p36, 4p15, 5q12, 5q23, 6p22-24, 6q16, 6q25-26, 7p21, 10q24, 12p12-13, 12q13, 16q12, 16q21-23, 17p13, 20q12-13, and Xq26-28. After the addition of further markers, the maximum nonparametric linkage score increased from 3.5 to 3.94 at 12p12-13 (D12S77; P = 0.0002) and from 3.07 to 3.70 at 6p22-24 (D6S285; P = 0.0005). CONCLUSION: This study is the first systematic genome screen in Behçet's disease and provides evidence of linkage to several non-HLA susceptibility loci in a cohort of Turkish multicase families. This represents the first step toward the identification of novel Behçet's disease susceptibility genes.

Behcet Syndrome↗
PubMed2005

An evaluation of the decision tree format of the American College of Rheumatology 1987 classification criteria for rheumatoid arthritis: performance over five years in a primary care-based prospective study.

OBJECTIVE: The American College of Rheumatology (ACR) 1987 criteria for rheumatoid arthritis (RA) can be applied in 2 formats, a standard "x/y" list and a decision tree. This study evaluated the performance of the decision tree compared with the list approach in the ascertainment of RA in subjects with new-onset inflammatory polyarthritis (IP) over the first 5 years of observation. Moreover, the use of clinical surrogates to substitute for missing rheumatoid factor (RF) and radiologic erosion data was assessed for validity and for its influence on the resulting RA prevalence estimates. METHODS: In this population-based prospective study, 848 subjects with new-onset IP were interviewed and examined at baseline, with followup at 1, 2, 3, and 5 years. RF and erosion status were determined at prespecified time points. The list criteria were applied cumulatively, while the decision tree was applied cross-sectionally using either data surrogates or the actual reported data. RA prevalence in the 848 subjects and agreement in classification between the 2 methods was assessed at each time point. The influence of using clinical surrogates on RA prevalence estimates at 5 years and the agreement between surrogate and real results were also analyzed. RESULTS: At baseline, RA prevalence was higher using the decision tree compared with the list approach (63% versus 47%; P = 0.0001); by 5 years of followup, RA estimates were approximately equal (69% versus 72%) and agreement between the approaches was good (kappa = 0.67). The use of surrogates had little influence on RA prevalence at 5 years, although substitution of metacarpophalangeal joint swelling for erosion produced a higher RA prevalence estimate (78% versus 70%). Although there was only weak agreement between surrogate and real data, the use of the surrogate data provided good to very good agreement between the approaches in categorizing subjects as RA positive (kappa = 0.61-0.72). CONCLUSION: Over 5 years, the 2 formats of the ACR criteria for RA performed similarly, with no important differences between them. The use of surrogates for missing radiologic and serologic data did not have any major influence on disease classification. Although the RA criteria were not originally derived from subjects with early disease in a population setting, this study shows that the use of the decision tree approach with the option of substituting clinical surrogates for missing laboratory data is an appropriate alternative to the conventional list approach.

Adult↗