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Biomedical subjects

Deborah P M Symmons

Publications and source records attributed to Deborah P M Symmons.

At least 19 recordsLinked to original sources
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

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

Developing classification criteria for peripheral joint psoriatic arthritis. Step I. Establishing whether the rheumatologist's opinion on the diagnosis can be used as the "gold standard".

OBJECTIVE: The study of psoriatic arthritis (PsA) is hampered by the absence of a widely accepted, validated case definition. We investigated whether the physician's opinion can be used as a gold standard when developing classification criteria for peripheral joint PsA. METHODS: UK rheumatologists who had published on PsA and attendees at 3 international meetings on PsA held in the UK were polled by questionnaire. There were 3 phases. The first questionnaire asked whether rheumatologists believed in the construct of PsA. The second survey developed a list of features thought to distinguish patients with PsA from other forms of peripheral arthritis. The final phase was development of a series of 61 "paper" patients with various combinations of the features of PsA. The paper patients were assessed by 15 rheumatologists who were asked whether, in their opinion, the patient had PsA. Latent class analysis was used to identify subgroups of patients and cross-tabulations were used to identify which clinical and laboratory features were associated with each subgroup. RESULTS: Rheumatologists agreed on the construct of PsA and that not all patients with psoriasis and an inflammatory polyarthritis have PsA. Latent class analysis identified 3 classes, corresponding to definite PsA; a middle group that was very likely to be given a diagnosis of PsA by some rheumatologists (high diagnosers), but unlikely to be given the diagnosis by others (low diagnosers); and a third group corresponding to "probably not PsA." CONCLUSION: For the group of patients with "definite PsA" the physician's opinion can be taken as the gold standard when developing classification criteria. However, for patients in the "middle group" there will always be disagreement with the gold standard whether the standard is based on the opinion of the high diagnosers or the low diagnosers.

Arthritis, Psoriatic↗
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

The prevalence and incidence of biopsy-proven lupus nephritis in the UK: Evidence of an ethnic gradient.

OBJECTIVE: Renal involvement is a major complication of systemic lupus erythematosus (SLE) and is a strong determinant of morbidity and mortality. There have been no previous studies of the epidemiology of lupus nephritis. Our aim was to establish the prevalence and incidence of biopsy-proven lupus nephritis in the northwest of England in 2001 and to examine the influence of age, sex, and ethnicity. METHODS: Adults (age 18 years and older) with biopsy-proven lupus nephritis were identified from 5 sources: renal biopsy databases, dialysis/transplant databases, nephrologists' patients, clinic lists, and lupus patient groups. The denominator data for the northwest of England were ascertained from the 2001 census. RESULTS: We identified 208 cases of biopsy-proven lupus nephritis (176 women, 32 men): the overall prevalence was 4.4 per 100,000 population (95% confidence interval [95% CI] 3.8-5.0), 7.1 per 100,000 (95% CI 6.1-8.2) in women, and 1.4 per 100,000 (95% CI 1.0-2.0) in men. The prevalence was significantly higher among women in the ethnic subgroups: 110.3 per 100,000 population (95% CI 55.0-197.3) in Chinese patients, 99.2 per 100,000 (95% CI 55.5-163.6) in Afro-Caribbean, 21.4 per 100,000 (95% CI 12.0-35.2) in Indo-Asian (Asians from the Indian subcontinent), and 5.6 per 100,000 (95% CI 4.7-6.7) in white patients. The overall annual incidence rate was 0.40 per 100,000 population per year (95% CI 0.24-0.63), with a rate of 0.68 (95% CI 0.40-1.10) in women and 0.09 (95% CI 0.01-0.32) in men. Capture-recapture methods did not suggest any additional cases. CONCLUSION: This first estimate of the prevalence and incidence of biopsy-proven lupus nephritis demonstrates dramatic differences in prevalence according to ethnicity, with an increasing gradient from the white to the Indo-Asian, Afro-Caribbean, and Chinese populations.

Adolescent↗
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↗
PubMed2006

Predicting persistent disabling low back pain in general practice: a prospective cohort study.

BACKGROUND: Patients may adopt active and/or passive coping strategies in response to pain. However, it is not known whether these strategies may also precede the onset of chronic symptoms and, if so, whether they are independent predictors of prognosis. AIM: To examine, in patients with low back pain in general practice, the prognostic value of active and passive coping styles, in the context of baseline levels of pain, disability and pain duration. DESIGN OF STUDY: Prospective cohort study. SETTING: Nine general practices in north west England. METHOD: Patients consulting their GP with a new episode of low back pain were recruited to the study. Information on coping styles, pain severity, disability, duration, and a brief history of other chronic pain symptoms was recorded using a self-completion postal questionnaire. Participants were then sent a follow-up questionnaire, 3 months after their initial consultation, to assess the occurrence of low back pain. The primary outcome was persistent disabling low back pain, that is, low back pain at 3-month follow-up self-rated as >or=20 mm on a 100 mm visual analogue scale, and >or=5 on the Roland and Morris Disability Questionnaire. RESULTS: A total of 974 patients took part in the baseline survey, of whom 922 (95%) completed a follow-up questionnaire; 363 individuals (39%) reported persistent disabling pain at follow-up. Persons who reported high levels of passive coping experienced a threefold increase in the risk of persistent disabling low back pain (relative risk [RR] = 3.0; 95% confidence interval [CI] = 2.3 to 4.0). In contrast, active coping was associated with neither an increase nor a decrease in the risk of a poor prognosis. After adjusting for baseline pain severity, disability, and other measures of pain and pain history, persons who reported a high passive coping score were still at 50% increased risk of a poor outcome (RR = 1.5; 95% CI = 1.1 to 2.0). CONCLUSION: Patients who report passive coping strategies experience a significant increase in the risk of persistent symptoms. Further, this risk persists after controlling for initial pain severity and disability. The identification of this low back pain subgroup may help target future treatments to those at greatest risk of a poor outcome.

Adaptation, Psychological↗
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↗
PubMed2005

Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort.

OBJECTIVE: To test the hypothesis that the C-reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP). METHODS: Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD. RESULTS: The median followup was 10.1 years (interquartile range 9.3-10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (> or=5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2-13.4) for men, and HR 4.22 (95% CI 1.4-12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7-32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4-7.6]). CONCLUSION: The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new-onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD.

Adult↗
PubMed2005

Does early rheumatoid arthritis exist?

The 'life cycle' of established rheumatoid arthritis can be divided into four phases. The first is the period leading up to the onset of arthritis. The second is the period during which persistence or remission is determined. The third is the evolution into a specific form of inflammatory arthritis, and the fourth is the outcome/severity of that arthritis. In some patients, these four phases follow in rapid succession; however, in other patients, the time course is prolonged over several months or years. This chapter explores the hypothesis that these four phases are distinct in the majority of patients, and that different genetic and environmental factors influence the various phases. It investigates the suggestion that a defect in the hypothalamic-pituitary-adrenal axis may underlie the persistence of inflammatory arthritis. It suggests that the term 'early rheumatoid arthritis' is not appropriate and that patients either have established rheumatoid arthritis or an undifferentiated inflammatory arthritis.

Arthritis, Rheumatoid↗
PubMed2005

Dietary beta-cryptoxanthin and inflammatory polyarthritis: results from a population-based prospective study.

BACKGROUND: Epidemiologic studies suggest that the antioxidant potential of dietary carotenoids may protect against the oxidative damage that can result in inflammation. OBJECTIVE: We investigated the hypothesis that some dietary carotenoids are associated with a reduced risk of developing inflammatory polyarthritis (IP). DESIGN: The European Prospective Investigation of Cancer Incidence (EPIC)-Norfolk study is a population-based, prospective study of >25,000 subjects who completed a baseline 7-d diet diary and were followed up to identify new cases of IP, which was defined as synovitis that affected > or = 2 joint groups. Dietary carotenoid intakes were computed from the diet diaries of these subjects, and a nested, case-control analysis was undertaken to compare carotenoid intake between case subjects and age- and sex-matched control subjects. RESULTS: Eighty-eight incident cases of IP that occurred in the population surveyed were ascertained via the Norfolk Arthritis Register. The mean daily intakes of zeaxanthin and beta-cryptoxanthin were 20% and 40% lower, respectively, in the cases than in the 176 controls, but there were no significant differences in the intakes of either lutein or lycopene. Those subjects in the top one-third of intake of zeaxanthin and beta-cryptoxanthin were at a lower risk of developing IP than were subjects in the lowest one-third [odds ratios (95% CI): 0.48 (0.24, 0.94) and 0.51 (0.25, 1.02) for zeaxanthin and beta-cryptoxanthin, respectively]. The association with beta-cryptoxanthin was significant after adjustments were made for total energy and protein intakes and for cigarette smoking. CONCLUSION: These data are consistent with previous evidence showing that a modest increase in beta-cryptoxanthin intake, equivalent to one glass of freshly squeezed orange juice per day, is associated with a reduced risk of developing inflammatory disorders such as rheumatoid arthritis.

Aged↗
PubMed2005

The relationship between social deprivation, disease outcome measures, and response to treatment in patients with stable, long-standing rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) with lower socioeconomic status (SES) are known to have more severe disease, more comorbidity, and higher mortality. It is not known whether SES influences response to treatment in RA. We examined the relationship between area of residence (as a surrogate for SES) and baseline outcome measures and response to treatment, using data from the British Rheumatoid Outcome Study Group randomized controlled trial of aggressive versus symptomatic treatment of long-standing, stable RA. METHODS: A total of 466 patients from 5 centers were recruited to the trial. Baseline data included age, sex, smoking status, and comorbidity. Patients were assigned a Townsend score (a measure of social deprivation) according to their area of residence. Outcome measures including the Disease Activity Score (DAS28), Health Assessment Questionnaire, Medical Outcomes Study Short Form-36, and EuroQol (EQ5D) were recorded at the beginning and end of the 3 year trial. The baseline, 3 year values, and change data were examined by Townsend quintile adjusting for each treatment arm. RESULTS: Significant relationships between increasing social deprivation by area of residence and higher disease activity, higher pain, poorer physical function, poorer emotional aspects of mental health, and lower quality of life were found at baseline (adjusted for age, sex, disease duration, current smoking, treatment center, and treatment group). During the 3 year trial period, patients from the most deprived areas showed greater improvement, with statistically significant greater improvement on DAS28 (p = 0.041) and 28 tender joint count (p = 0.015). CONCLUSION: Area of residence is related to the severity of RA at recruitment and is a predictor of response in a clinical trial situation. The results suggest that measures of SES should be recorded for patients enrolled in clinical trials, longitudinal observational studies, and in the clinical setting.

Aged↗
PubMed2005

Reconciling subject differences in recruitment to clinical trials and clinical practice.

The special interest group on Reconciling Subject Differences was centered around the issue that the results from randomized clinical trials do not predict response to therapies in clinical practice, and around the hypothesis that this might be explained by differences in subjects selected for clinical trials compared to those treated in routine practice.

Arthritis, Rheumatoid↗