Search PubMed⌕ Search

Biomedical subjects

Alan J Silman

Publications and source records attributed to Alan J Silman.

At least 37 records · Page 2Linked to original sources
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

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

Onset of neck pain after a motor vehicle accident: a case-control study.

OBJECTIVE: To assess the relative contribution of constitutional (individual) factors, pre-accident health, psychological and workplace psychosocial factors, and accident related (mechanical) factors in the development of neck pain (whiplash) following a motor vehicle accident. METHODS: We conducted a case-control study of drivers (ages 17-70 yrs) who reported a motor vehicle accident to their insurance company. A self-report mailed questionnaire retrospectively collected information on the driver's pre- and post-accident health, details of the accident, and other exposure data. Case/control status (post-accident neck pain) was ascertained using a preshaded manikin. RESULTS: In total, 26% of drivers reported post-accident neck pain. Women, younger individuals, and those with a history of neck pain were more likely to report neck pain following their accident (OR 1.50, 95% CI 0.98, 2.28; OR 1.62, 95% CI 0.96, 2.74; OR 1.75, 95% CI 1.09, 2.81, respectively). In addition, a number of accident related and psychosocial factors were independently associated with reporting post-accident neck pain: collision from behind (OR 2.55, 95% CI 1.41, 4.62); vehicle stationary at impact (OR 1.93, 95% CI 1.12, 3.33); collision severity (upper vs lowest tertile: OR 16.1, 95% CI 8.64, 30.1); not being at fault (OR 2.61, 95% CI 1.49, 4.59); and monotonous work (OR 2.19, 95% CI 1.19, 4.04). Based on these 8 factors, the likelihood of having neck pain increased from 7% with < or = 2 risk factors to 62% with > or = 5. CONCLUSION: Development of neck pain after a motor vehicle accident is a complex phenomenon resulting from the combined effects of constitutional, mechanical, and psychosocial factors. Using 8 such variables it is possible to identify those at high risk of developing neck pain.

Accidents, Traffic↗
PubMed2005

Minimal disease activity for rheumatoid arthritis: a preliminary definition.

Agreement on response criteria in rheumatoid arthritis (RA) has allowed better standardization and interpretation of clinical trial reports. With recent advances in therapy, the proportion of patients achieving a satisfactory state of minimal disease activity (MDA) is becoming a more important measure with which to compare different treatment strategies. The threshold for MDA is between high disease activity and remission and, by definition, anyone in remission will also be in MDA. True remission is still rare in RA; in addition, the American College of Rheumatology definition is difficult to apply in the context of trials. Participants at OMERACT 6 in 2002 agreed on a conceptual definition of minimal disease activity (MDA): "that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations." To prepare for a preliminary operational definition of MDA for use in clinical trials, we asked rheumatologists to assess 60 patient profiles describing real RA patients seen in routine clinical practice. Based on their responses, several candidate definitions for MDA were designed and discussed at the OMERACT 7 in 2004. Feedback from participants and additional on-site analyses in a cross-sectional database allowed the formulation of 2 preliminary, equivalent definitions of MDA: one based on the Disease Activity Score 28 (DAS28) index, and one based on meeting cutpoints in 5 out the 7 WHO/ILAR core set measures. Researchers applying these definitions first need to choose whether to use the DAS28 or the core set definition, because although each selects a similar proportion in a population, these are not always the same patients. In both MDA definitions, an initial decision node places all patients in MDA who have a tender joint count of 0 and a swollen joint count of 0, and an erythrocyte sedimentation rate (ESR) no greater than 10 mm. If this condition is not met: * The DAS28 definition places patients in MDA when DAS28 < or = 2.85; * The core set definition places patients in MDA when they meet 5 of 7 criteria: (1) Pain (0-10) < or = 2; (2) Swollen joint count (0-28) < or = 1; (3) Tender joint count (0-28) < or = 1; (4) Health Assessment Questionnaire (HAQ, 0-3) < or = 0.5; (5) Physician global assessment of disease activity (0-10) < or = 1.5; (6) Patient global assessment of disease activity (0-10) < or = 2; (7) ESR < or = 20. This set of 2 definitions gained approval of 73% of the attendees. These (and other) definitions will now be subject to further validation in other databases.

Arthritis, Rheumatoid↗
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↗
PubMed2005

Scleroderma--developing measures of response.

The scleroderma research community continued its focus on the development and proper validation of the outcome measures for clinical trials in scleroderma during the special interest group meeting at OMERACT 7. Deliberations focused on progress in the assessment of gastrointestinal disease, renal physiology, vascular damage, and the unique challenges inherent in studying pediatric patients with scleroderma.

Adolescent↗
PubMed2004

When should the doctor order a spine X-ray? Identifying vertebral fractures for osteoporosis care: results from the European Prospective Osteoporosis Study (EPOS).

UNLABELLED: Vertebral fractures are common but usually remain unrecognized in primary care. Data from 2908 women and 2653 men in the EPOS study were used to derive algorithms to indicate the need for a spine X-ray to identify a fracture using easily elicited determinants. At a sensitivity of 50% for identifying cases, the specificity was increased from 50% to 78% in women and from 50% to 72% in men compared with a random allocation of X-rays. Use of X-rays can be optimized by selecting patients at high risk using a short screening procedure. INTRODUCTION: Previous osteoporotic fracture is an independent risk factor for further fractures and an indication for treatment. Vertebral fractures are the most common osteoporotic fractures before age 75, accounting for 48% of all fractures in men and 39% in women over 50. They usually remain unrecognized, so many patients requiring treatment are denied it, doubling their risk of a further fracture. Our objective was to develop an efficient algorithm indicating the need for an X-ray. MATERIALS AND METHODS: Data from 2908 women and 2653 men >or=50 years of age in the European Prospective Osteoporosis Study (EPOS) were analyzed. Lateral thoracic and lumbar spine radiographs were taken at baseline and at an average of 3.8 years later. Prevalent fractures were qualitatively diagnosed by an experienced radiologist. Fracture risk was modeled as a function of age, statural height loss since age 25, gender, and fracture history including limb fractures in the last 3 years using negative binomial regression. Receiver operating characteristic (ROC) curves were used to summarize a model's predictive ability, and a prediction algorithm was devised to identify those most likely to have a fracture. RESULTS: In a multivariate model for women, the risk of prevalent vertebral fracture significantly increased with age (RR, 1.67 [95% CI, 1.46, 1.93] per decade), statural height loss (1.06, [1.03, 1.10] per centimeter decrease), self-reported history of spine fracture (7.52 [5.52, 10.23]), and history of other major fracture (1.83 [1.46, 2.28]). Higher body weight reduced risk (0.86 [0.79, 0.95] per 10-kg increase). In men, the respective RR estimates were as follows: age (1.32 [1.18, 1.49]); height loss (1.06 [1.04, 1.09]); self-reported spine fracture (5.05 [3.69, 6.90]); other major fracture (1.42 [1.12, 1.81]); and weight (0.86 [0.79, 0.94]). Using algorithms based on these easily elicited determinants, specificity was increased from 50% to 78% in women and from 50% to 72% in men at a sensitivity of 50% compared with a random allocation of X-rays. At a sensitivity of 75%, the specificity was 50% in women and 40% in men. Inclusion of hip BMD (femoral neck or trochanter), measured in 1360 women and 1046 men, significantly improved the area under the ROC curves by 4% in women (p < 0.002) but not in men (p > 0.350). Spine BMD, measured in 982 women and 847 men, produced a significant 5% AUC improvement in women (p = 0.007) but not in men (p = 0.554). CONCLUSION: A woman 65 years of age with one vertebral fracture has a one in four chance of another fracture over 5 years, which can be reduced to one in eight by treatment. Positive treatment decisions are often contingent on identifying a vertebral fracture. Selective use of lateral vertebral X-rays can be optimized using a 2-minute screening procedure administered by a nurse.

Age Factors↗
PubMed2004

Psychological stress and fibromyalgia: a review of the evidence suggesting a neuroendocrine link.

The present review attempts to reconcile the dichotomy that exists in the literature in relation to fibromyalgia, in that it is considered either a somatic response to psychological stress or a distinct organically based syndrome. Specifically, the hypothesis explored is that the link between chronic stress and the subsequent development of fibromyalgia can be explained by one or more abnormalities in neuroendocrine function. There are several such abnormalities recognised that both occur as a result of chronic stress and are observed in fibromyalgia. Whether such abnormalities have an aetiologic role remains uncertain but should be testable by well-designed prospective studies.

Animals↗
PubMed2004

A meta-analysis of prior corticosteroid use and fracture risk.

UNLABELLED: The relationship between use of corticosteroids and fracture risk was estimated in a meta-analysis of data from seven cohort studies of approximately 42,000 men and women. Current and past use of corticosteroids was an important predictor of fracture risk that was independent of prior fracture and BMD. INTRODUCTION: The aims of this study were to validate that corticosteroid use is a significant risk factor for fracture in an international setting and to explore the effects of age and sex on this risk. MATERIALS AND METHODS: We studied 42,500 men and women from seven prospectively studied cohorts followed for 176,000 patient-years. The cohorts comprised the EPOS/EVOS study, CaMos, the Rotterdam Study, Dubbo Osteoporosis Epidemiology Study (DOES), and prospective cohorts at Sheffield, Rochester, and Gothenburg. The effect of ever use of corticosteroids, BMD, age, and sex on all fracture, osteoporotic fracture, and hip fracture risk alone was examined using Poisson regression in each cohort and for each sex. The results of the different studies were merged from the weighted beta coefficients. RESULTS: Previous corticosteroid use was associated with a significantly increased risk of any fracture, osteoporotic fracture, and hip fracture when adjusted for BMD. Relative risk of any fracture ranged from 1.98 at the age of 50 years to 1.66 at the age of 85 years. For osteoporotic fracture, the range of relative risk was 2.63-1.71, and for hip fracture 4.42-2.48. The estimate of relative risk was higher at younger ages, but not significantly so. No significant difference in risk was seen between men and women. The risk was marginally and not significantly upwardly adjusted when BMD was excluded from the model. The risk was independent of prior fracture. In the three cohorts that documented current corticosteroid use, BMD was significantly reduced at the femoral neck, but fracture risk was still only partly explained by BMD. CONCLUSION: We conclude that prior and current exposure to corticosteroids confers an increased risk of fracture that is of substantial importance beyond that explained by the measurement of BMD. Its identification on an international basis validates the use of this risk factor in case-finding strategies.

Adrenal Cortex Hormones↗
PubMed2004

Mechanical injury and psychosocial factors in the work place predict the onset of widespread body pain: a two-year prospective study among cohorts of newly employed workers.

OBJECTIVE: Mechanical injury has been postulated as a risk factor for widespread pain, although to date, the evidence is weak. The aim of this study was to determine whether repeated exposure to mechanical trauma in the work place predicts the onset of widespread pain and to determine the relative contribution of mechanical trauma compared with psychosocial factors. METHODS: In this prospective cohort study of 1,081 newly employed subjects in 12 diverse occupational settings, we collected detailed information on mechanical exposure, posture, physical environment, and psychosocial risk factors in the work place. Study questionnaires were completed at baseline and at 12 and 24 months. Individuals free of widespread pain at baseline and 12 months were eligible for followup. Generalized estimating equations were used to determine which factors predicted the new onset of widespread pain. RESULTS: Of the 1,081 baseline respondents, 896 were free of widespread pain and were eligible for further study. Of these 896 subjects, 708 and 520 responded at 12 months and 24 months, respectively. The rates of new-onset widespread pain were 15% at 12 months and 12% at 24 months. Several work place mechanical and posture exposures predicted the new onset of widespread pain: lifting >15 lbs with 1 hand, lifting >24 lbs with 2 hands, pulling >56 lbs, prolonged squatting, and prolonged working with hands at or above shoulder level. Of the psychosocial exposures, those who reported low job satisfaction, low social support, and monotonous work had an increased risk of new-onset widespread pain. In multivariate analysis, monotonous work and low social support were found to be the strongest independent predictors of symptom onset. CONCLUSION: Our findings demonstrate that the prevalence of new-onset widespread pain was high, but among this young, newly employed work force, both physical and psychosocial factors played an important role.

Adult↗
PubMed2004

Evidence for a novel rheumatoid arthritis susceptibility locus on chromosome 6p.

OBJECTIVE: To investigate whether the large linkage peak on chromosome 6p harbors rheumatoid arthritis (RA) susceptibility loci in addition to the well-characterized HLA-DRB1 gene. METHODS: DNA samples obtained from 377 UK RA affected sibling pair (ASP) families, comprising test (181 ASPs) and replication (196 ASPs) cohorts, were used for linkage analysis. Three hundred eighty-four patients with RA derived from a subset of 192 ASPs were compared with a panel of 288 unrelated healthy controls for association studies. Samples were genotyped for 35 microsatellites and 25 single-nucleotide polymorphisms (SNPs). RESULTS: In the test cohort, the maximum logarithm of odds (LOD) score was obtained over D6S1260 (LOD 7.1). Evidence for linkage to the telomeric portion of the peak was increased in subsets of ASPs in which both individuals had erosive disease or both carried 2 copies of the shared epitope. HLA-A, HLA-DRB1, and 8 additional markers showed evidence of linkage in the presence of association with RA (using the extended transmission disequilibrium test [ETDT]). The positive ETDT result for 2 adjacent markers (D6S1665 and 210901-4) mapping to the telomeric end of the linked region ( approximately 11 Mb from DRB1) was replicated (for D6S1665) in the second cohort of ASPs. Haplotypic overtransmission of pairwise combinations between D6S1665*7 and 210901-4*4 was identified through the TDTPhase program. Multipoint conditional analysis showed this effect to be independent of HLA-DRB1. SNP-based association studies of the region identified a 4-marker haplotype in the DEK gene that was significantly associated with RA (P = 0.009). CONCLUSION: Evidence has been presented for an RA susceptibility locus mapping under the linkage peak on 6p, 11 Mb telomeric of HLA-DRB1. Preliminary association data implicate the gene DEK.

Arthritis, Rheumatoid↗
PubMed2004

Dietary risk factors for the development of inflammatory polyarthritis: evidence for a role of high level of red meat consumption.

OBJECTIVE: To investigate the association of red meat and other specific dietary components in predicting the development of inflammatory polyarthritis. METHODS: This nested case-control study was conducted within a prospective population-based study of cancer incidence (European Prospective Investigation of Cancer in Norfolk [EPIC-Norfolk]). EPIC-Norfolk recruited 25,630 subjects ages 45-75 years between 1993 and 1997. Dietary intake was assessed at baseline using a 7-day food diary, and the information was analyzed using dietary analysis software. Patients with new cases of inflammatory polyarthritis were identified by linkage with the Norfolk Arthritis Register, a primary care-based inception study of inflammatory polyarthritis, and were matched for age and sex to 2 controls from EPIC-Norfolk. The risk for development of inflammatory polyarthritis was compared between subjects in the highest and lowest tertiles of dietary intake using conditional logistic regression and was expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Between 1993 and 2002, 88 new patients with inflammatory polyarthritis were identified and matched with 176 controls. Among patients, the level of red meat intake was higher (P = 0.04) and that of vitamin C was lower (P = 0.03) compared with intake among controls, but no difference in total energy intake was observed. Patients were more likely to be smokers. After adjusting for total energy intake, smoking, and other possible dietary confounders, subjects with the highest level of consumption of red meat (OR 1.9, 95% CI 0.9-4.0), meat and meat products combined (OR 2.3, 95% CI 1.1-4.9), and total protein (OR 2.9, 95% CI 1.1-7.5) were at an increased risk for inflammatory polyarthritis. CONCLUSION: A high level of red meat consumption may represent a novel risk factor for inflammatory arthritis or may act as a marker for a group of persons with an increased risk from other lifestyle causes.

Aged↗
PubMed2004

The Cheshire Foot Pain and Disability Survey: a population survey assessing prevalence and associations.

Previous foot studies have consistently reported high prevalence estimates in self-reported foot disorders. Few population studies, however, have attempted to assess the impact of foot problems in terms of pain and disability so that the burden associated with foot pain is unknown. A cross-sectional postal survey was conducted on a random community sample of 4780 individuals with 3417 (84%) responding. Subjects reporting foot pain in the past month, current pain and marking one item on the Manchester Foot Pain and Disability Index were classified as having disabling foot pain. Those with disabling foot pain and a random sample with no symptoms (matched for age and gender) received a follow-up interview and standardised foot examination. Self-reported nail problems, corns and callosities, swollen feet, foot deformities and recent foot injuries were found to be associated with disabling foot pain. Foot disability was also associated with pain in the shoulder, axial skeleton, hip/upper leg and knee along with other indicators of poor general health. Clinician diagnosed foot problems associated with disabling foot pain were swollen feet, knee and foot joint tenderness. Only 36% of persons with disabling foot pain received professional foot treatment in the 6 months preceding the survey. The results showed that 323/3417 (9.5%) reported symptoms of disabling foot pain and that this condition is likely to be multi-factorial in origin. Further work is necessary to understand more about the extent and type of unmet need and on how patients presenting with symptoms of disabling foot pain should best be managed.

Adolescent↗
PubMed2004

Radiographic features of lumbar disc degeneration and self-reported back pain.

OBJECTIVE: To characterize the occurrence of radiographic features of lumbar disc degeneration including the presence of osteophytes, endplate sclerosis, and disc space narrowing and to determine their relationship with self-reported back pain. METHODS: Subjects aged 50 years and over were recruited from a primary care based community health index in Aberdeen, UK. Subjects were invited to complete an interviewer administered questionnaire and to have lateral spinal radiographs performed. The questionnaire included questions concerning the occurrence of back pain, both ever and in the past year. The inter-vertebral disc spaces (L1/2 to L4/5) were evaluated for the presence and severity of anterior osteophytes, endplate sclerosis, and disc space narrowing using a semi-quantitative score (grade 0-3). Logistic regression was used to determine the association between these individual radiographic features of lumbar disc degeneration (using for each feature, the most severely affected vertebra) and back pain, with adjustments made for age and gender. RESULTS: There were 286 men (mean age 65.3 years), and 299 women (mean age 65.2 years) with spinal radiographs. Osteophytes were the most frequent radiographic feature. Osteophytes and endplate sclerosis were more frequent in men than women, but there was no gender difference in the frequency of disc space narrowing. All radiographic features increased in frequency with age; for osteophytes this was true only after excluding mild (grade 1) osteophytes. Compared to those without, those with disc space narrowing were more likely to report back pain both ever, [odds ratio (OR) = 2.1; 95% confidence interval (CI): 1.5 to 3.0] and in the past year (OR = 1.7) with the strength of the association increasing with increasing severity of narrowing. Endplate sclerosis was not linked with back pain although moderate (grade 2) sclerosis was associated with back pain, both ever and in the past year. Compared to those without, or those with mild osteophytes, those with more severe osteophytes (grade > 1) were more likely to report back pain ever (OR = 1.7; 95% CI: 1.2 to 2.5). CONCLUSION: These data highlight the frequent occurrence, and the increase in frequency with age, of the individual radiographic features of lumbar disc degeneration in population samples of men and women. Disc space narrowing appeared more strongly associated with back pain than the other radiographic features.

Aged↗
PubMed2003

Predicting the onset of forearm pain: a prospective study across 12 occupational groups.

OBJECTIVE: To determine, among workers free of forearm pain, the role of mechanical and psychosocial factors in predicting future onset. METHODS: A prospective cohort study was conducted among 782 newly employed workers from 12 occupational groups. At baseline, a cohort of 782 workers free of forearm pain was identified and measurement was made about physical and psychosocial aspects of their job and working environment. Subjects were recontacted after 1 year to determine new onsets of forearm pain. A sample of those reporting new onset forearm pain underwent a structured examination of the upper limb. RESULTS: One year after baseline, 666 (85%) subjects were followed up. The overall prevalence of new onset forearm pain was 8.3% (n = 55). The strongest mechanical risk factor was frequent repetitive movements of the arm or wrist (odds ratio [OR] 2.9, 95% confidence interval [95% CI] 1.6-5.2). The strongest psychosocial risk factors were work considered monotonous at least half of the time (OR 3.0, 95% CI 1.6-5.7) or work with little autonomy (OR 2.6, 95% CI 1.1-6.1). Three specific independent risk factors (monotonous work, repetitive wrist movement, working with hands above shoulder level) could distinguish groups of subjects at substantially different risks of onset. CONCLUSIONS: Along with repetitive movements of the arms and wrists, mechanical postural factors and psychosocial factors also are important risk factors for onset of forearm pain. Our study emphasizes the multifactorial nature of risks for onset of forearm pain, and provides leads as to possible mechanisms for prevention.

Cohort Studies↗