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Biomedical subjects

A Silman

Publications and source records attributed to A Silman.

At least 55 records · Page 3Linked to original sources

Breast-feeding and postpartum relapse in women with rheumatoid and inflammatory arthritis.

OBJECTIVE: To test the hypothesis that breast-feeding increases the risk of postpartum flare in inflammatory polyarthritis. METHODS: We compared disease activity during pregnancy and at 6 months postpartum among 49 non-breast-feeders, 38 first-time breast-feeders, and 50 repeat breast-feeders. RESULTS: After we adjusted for possible confounders, including treatment, first-time breast-feeders had increased disease activity 6 months postpartum, based on self-reported symptoms, joint counts, and C-reactive protein levels. CONCLUSION: Postpartum flare may be induced by breast-feeding.

Adult↗

A two-stage, genome-wide screen for susceptibility loci in primary Raynaud's phenomenon.

OBJECTIVE: To identify chromosomal regions containing genes involved in the susceptibility to primary Raynaud's phenomenon (RP). METHODS: Six extended families with multiple individuals affected with primary RP (n = 37) were examined for linkage in a 2-stage, whole-genome screen, using a total of 298 microsatellite markers. RESULTS: Multipoint, nonparametric linkage analysis identified 5 areas of possible linkage, with a nominal level of significance of P < or = 0.05. Analysis of a finer map of markers in these regions defined the regions of linkage as 21.4 cM on 6q13-6q23.3 (D6S261; P = 0.0004), 10.2 cM on 7p22-7p15 (D7S664; P = 0.014), 1.6 cM on 9p23-9p22 (D9S156; P = 0.0075), 5.1 cM on 17p13.1-17p12 (D17S1791; P = 0.036), and 11.8 cM on Xp11.4-Xp11.23 (DXS8054; P = 0.006). Three potential candidate genes map to these regions: the beta subunit of the muscle acetylcholine receptor and the serotonin 1B and 1E receptors. CONCLUSION: These results provide evidence of the presence and location of genes that are involved in the genetic susceptibility to primary RP.

Adolescent↗

Associations between demographic and disease-related variables and disability over the first five years of inflammatory polyarthritis: a longitudinal analysis using generalized estimating equations.

OBJECTIVES: To investigate whether the relationship between demographic and disease-related variables and disability is constant during the first five years of inflammatory polyarthritis (IP) and to identify the contribution from involvement of specific joint areas to overall disability. METHODS: 684 patients referred to the Norfolk Arthritis Register were followed for five years using the Health Assessment Questionnaire (HAQ). The relationship between disability and demographic and clinical variables was analyzed using a multi-level modelling approach. RESULTS: Female gender, older age at symptom onset (> or = 64 years), joint involvement at six specific sites, joint tenderness and the number of deformed joints were all independently associated with disability (HAQ > or = 1.00). Similar results were obtained using a more stringent cut-off (HAQ > or = 1.50) or when analysis was restricted to the 325 patients who satisfied the 1987 ARA list criteria for rheumatoid arthritis. CONCLUSION: Disability, as measured by the HAQ, was associated with a large number of independent factors over the first five years of disease.

Adult↗

Radiographic change is common in new presenters in primary care with hip pain. PCR Hip Study Group.

OBJECTIVE: To determine the prevalence of radiographic osteoarthritis in subjects with hip pain newly presenting to primary care. METHODS: The study was cross-sectional in design, set in 35 general practices across the UK. It included 195 men and women aged 40 yr and over (median 63 yr) presenting with a new episode of hip pain. Hip radiographs were scored for minimum joint space (MJS) and overall-Croft's modification of the Kellgren and Lawrence (Croft)-grade of osteoarthritis. RESULTS: In all, definite evidence of radiographic change in the painful joint was common: Croft grade > or =2 in 44%, > or =3 in 34%. MJS of 2.5 mm or less was seen in 30% of whom half were below 1.5 mm. There were no significant gender differences in radiographic severity. CONCLUSIONS: Radiographic change is common in patients newly presenting with hip pain and many already have advanced disease.

Adult↗

Health impact of pain in the hip region with and without radiographic evidence of osteoarthritis: a study of new attenders to primary care. The PCR Hip Study Group.

OBJECTIVES: To assess the health impact of hip pain at the time of first presentation to primary care, and the influence on this of radiographic evidence of osteoarthritis. SUBJECTS AND METHODS: Cross sectional survey of 195 patients (63 male, 132 female), aged 40 years and over, presenting with a new episode of hip pain, recruited from 35 general practices across the UK. Health status at presentation was determined by a structured questionnaire on symptoms, healthcare use, and health related quality of life (SF-36). Pelvic radiographs were assessed blindly for hip osteoarthritis using standard scoring systems. RESULTS: The overall impact on health was substantial. Before their first consultation, three quarters of patients needed analgesics, half used topical creams or ointments, and one in eight used a walking stick. Most of these impact measures were, however, unrelated to the degree of radiographic change, though use of a walking stick was increased in those with the most severe damage. Health status, as judged by the SF-36, was also impaired for measures of physical function and pain, but the impact on the "mental health", "general health", and "vitality" dimensions was small. There was a weak relation between the SF-36 scores and radiographic change, with many domains unrelated to the severity of radiographic damage. CONCLUSIONS: This study is the first to show the therapeutic impact and pattern of impairment in health status resulting from hip pain at the time of first presentation to the healthcare services. Unlike many regional pain syndromes seen in primary care, such as back pain, hip pain does not impact on wider aspects of quality of life, such as general health status, mental health, or vitality. Furthermore, any impact of hip pain in this group is not markedly influenced by the degree of structural damage. Further follow up is required to determine whether such damage influences the persistence of any adverse impact.

Adult↗

The existence of geographical clusters of cases of inflammatory polyarthritis in a primary care based register.

OBJECTIVES: To determine whether there is any evidence that there are spatial clusters of rheumatoid arthritis in particular, and inflammatory arthritis in general. METHODS: Setting was a population based incidence register of inflammatory arthritis: the Norfolk Arthritis Register (NOAR). All cases identified between 1990-1995 were mapped to place of residence. Statistical evidence of clustering was determined by calculating Poisson probabilities in putative areas. RESULTS: Three clusters were identified including one small area (population 85) where five unrelated cases developed during this time period. There was no obvious greater disease homogeneity within clusters and no common environmental factors were identified. CONCLUSION: Rare clusters of inflammatory polyarthritis do occur. Their significance and cause remain to be elucidated.

Adult↗

Maternal-fetal HLA incompatibility and the course of inflammatory arthritis during pregnancy.

OBJECTIVE: Studies indicate that maternal-fetal incompatibility of HLA-DR and DQ antigens may be associated with a decreased risk of disease activity during pregnancy in women with rheumatoid arthritis. We attempted to replicate these findings in a large cohort of women with inflammatory polyarthritis. METHODS: Women with an inflammatory polyarthritis were recruited during the last trimester of pregnancy and were interviewed and examined in their homes by a research nurse. Each woman provided a sample of blood as well as permission for a sample of cord blood to be taken at the time of birth. DNA was extracted from both maternal and cord blood and HLA-DRB1 and DQB1 typing performed. On the basis of known haplotypes found in Caucasian populations, DQA1 type was inferred wherever possible. RESULTS: Based on 110 or more maternal-fetal pairs, there was no increased occurrence of disease remission associated with maternal-fetal incompatibility of DRB1 alleles (remission ratio 0.7, 95% confidence interval 0.2-2.8), DQB1 alleles (remission ratio 1.2, 0.3-6.5), or DQA1 alleles (remission ratio 0.8,0.3-1.9). Results were similar whether maternal-fetal sharing was defined by broad allelic group or by specific alleles. CONCLUSION: Our results do not support the hypothesis that maternal-fetal HLA incompatibility contributes to remission of inflammatory arthritis during pregnancy.

Adult↗

[Normal values of vertebral heights in a representative population survey in Hungary].

The authors' aim was to derive Hungarian normal vertebral heights, height ratios and threshold values. The mean -3 SD of these ratios give them the threshold values for defining normal vertebraes. They examined the standardized vertebral morphometric measurements obtained in a cross-sectional population survey. Radiographs were taken according to standardized protocol and morphomeric measurements of anterior, central and posterior heights from thoracic 4 to lumbar 4 were made with a semiautomatic technique. The anterior, central, posterior I and posterior II height ratios were calculated for each vertebra. The mean and standard deviation of these ratios for each sex were derived using a statistical procedure to normalize the distribution. From the normally distributed vertebral height ratios the mean and standard deviation give us the threshold values for defining normal vertebraes. Anterior and central vertebral height ratios were smaller in males than females. The authors compared the ratios and threshold values in different European centers using the same method. The data confirm that vertebral height ratios vary between and within populations and the authors suggest that normal values for vertebral height ratios should be derived separately for males and females at each vertebral level. Having the normal values the knowledge of the Hungarian normal vertebral height ratios gives the possibility to carry on multicentre clinical, therapeutic and epidemiologic studies of vertebral deformity in Hungary. The authors suggest the widespread use of morphometry to evaluate vertebral osteoporosis because it can be done in every radiology unit, it is a cheap and easy method for measuring the bone mineral content.

Anthropometry↗

Quantifying the exact role of HLA-DRB1 alleles in susceptibility to inflammatory polyarthritis: results from a large, population-based study.

OBJECTIVE: To accurately determine the contributions of HLA-DRB1 alleles in explaining susceptibility to inflammatory polyarthritis in a large, true population-based cohort of new-onset cases. METHODS: A cohort of 680 consecutive patients with inflammatory polyarthritis, of whom 404 satisfied the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), was recruited from the population-based Norfolk Arthritis Register. All cases were compared with 286 local population controls. A standardized clinical assessment was performed on all patients. HLA-DRB1 phenotypes, including DR4 subtypes, were determined using a semiautomated, reverse dot-blot method. Results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: There was only a modest association (OR 1.8, 95% CI 1.4-2.4) between inflammatory polyarthritis and the presence of any shared epitope (SE) allele; the strongest individual risk was with DRB1*0404 (OR 3.5, 95% CI 1.8-6.8). Comparison of the genotypes demonstrated that the effect of being SE homozygous (OR 2.1, 95% CI 1.5-3.0) was only moderately greater than the effect of being SE heterozygous (OR 1.3, 95% CI 1.1-1.6). The exception to this was genotypic combinations that included HLA-DRB1*0404, which exhibited ORs ranging up to 18.0. There were no differences between either the phenotype or genotype data when the patients were stratified by RA status (defined by the ACR criteria). In contrast, the associations were substantially stronger in patients who were positive for rheumatoid factor. CONCLUSION: Previous studies had not been able to clarify whether the influence of HLA-DRB1 on RA was related to disease susceptibility or to disease severity and progression. These data on a unique population-based incident cohort suggest only weak effects on susceptibility, with the exception of the clearly distinct influence of HLA-DRB1*0404.

Alleles↗

The influence of HLA-DRB1 alleles and rheumatoid factor on disease outcome in an inception cohort of patients with early inflammatory arthritis.

OBJECTIVE: There are conflicting data concerning the role of HLA-DRB1 alleles in disease outcome in early rheumatoid arthritis. The exact role of these alleles in short-term outcome is determined in this large, prospective, population-based study. METHODS: We recruited 532 patients with inflammatory polyarthritis from the Norfolk Arthritis Register and typed their sera for HLA-DRB1 alleles using polymerase chain reaction-based methods. Disease outcome was assessed at 2 years in terms of persistent joint inflammation, functional disability, and radiologic erosions. Results are expressed as risk ratios (RR) with 95% confidence intervals (95% CI). RESULTS: There was no influence of HLA-DRB1 alleles, in any combination, on the likelihood of disease persistence, and only a modest effect on functional disability (Health Assessment Questionnaire score > or = 1). The most obvious effect was on the development of erosions (RR 1.9, 95% CI 1.4-2.6 for those who carried at least 1 DRB1 shared epitope [SE] allele), with slightly greater effects for those who were homozygous for SE-bearing alleles (RR 2.5, 95% CI 1.8-3.6). This effect of HLA-DRB1 was restricted to patients whose sera were negative for rheumatoid factor. Among patients with erosions, HLA-DRB1 had no influence on the severity of radiologic damage (defined as the number of eroded joints, or total Larsen score). CONCLUSION: These data do not support routine HLA-DRB1 screening of patients with early arthritis to identify those at risk for subsequent severe disease.

Adolescent↗

Projecting the need for hip replacement over the next three decades: influence of changing demography and threshold for surgery.

OBJECTIVES: To estimate the requirement for total hip replacement in the United Kingdom over the next three decades METHODS: Projection of age and sex specific hip replacements in the UK over 10 year intervals taking account of demographic change and the extrapolation of arthroplasty rates from Sweden; a country with recently introduced guidelines. RESULTS: Assuming no change in the age and sex specific arthroplasty rates, the estimated number of hip replacements will increase by 40% over the next 30 year period because of demographic change alone. The proportionate change will be substantially higher in men (51%) than women (33%), with a doubling of the number of male hip replacements in those aged over 85. Changes in the threshold for surgery may increase this further-up to double the current number. CONCLUSION: A sharp rise in hip replacements will be needed to satisfy needs in the UK population over the next 30 years.

Age Distribution↗

Disability in patients with early inflammatory polyarthritis cannot be "tracked" from year to year: an examination of the hypothesis underlying percentile reference charts.

OBJECTIVE: To determine whether disability in patients with early inflammatory polyarthritis (IP) can be charted or "tracked" over time. The disability score was also adjusted in an attempt to exclude the influence of current disease activity, with the aim of ascertaining that component of disability relating to other factors such as psychosocial factors and joint damage. METHODS: Four hundred thirty-three patients with early IP referred to the Norfolk Arthritis Register (NOAR) were followed annually using the Health Assessment Questionnaire (HAQ) for 5 years. HAQ scores at each year were divided into quartiles. The number of patients remaining in the same quartile from year to year was examined. The relationship between disease activity, assessed by swollen and tender joint counts, and HAQ was modelled, with the residual HAQ attributed to psychosocial factors and joint damage. RESULTS: From year to year, there was considerable within-individual variation in quartile, with only 48-65% of patients remaining in the same quartile. With increasing time, a greater proportion of patients remained in the same quartile. A statistically valid activity-adjusted HAQ score could not be computed. CONCLUSION: Disability in patients with early IP cannot be easily tracked over time. It is therefore not appropriate to construct longitudinal reference charts for disability in the early years, although it may be feasible for more established disease.

Adolescent↗

Preliminary core set of domains and reporting requirements for longitudinal observational studies in rheumatology.

Observational and longitudinal observational studies (LOS) provide essential information about the course and outcome of rheumatic disorders that cannot be provided by randomized controlled trials, and they constitute the major clinical scientific communication in rheumatology. There has been no consensus as to the full and appropriate content of LOS. This report defines a core set of domains and reporting requirements for LOS. At the 1998 OMERACT IV Conference a consensus process evaluated the literature of rheumatology in light of the constructs, variables, and outcomes of rheumatology by using introductory lectures, nominal groups, and plenary sessions. The result of this process was to identify 5 "core" domains that should be included in every LOS: Health Status, Disease Process, Damage, Mortality, and Toxicity/Adverse Reactions. Two additional domains, Work Disability and Costs, were recognized as important, but need not be used in all LOS. Eleven subdomains were identified that divided the domains into convenient clinical and conceptual units. A set of reporting requirements was also determined. The core recommendations, which follow on the WHO ICIDH-2 outline, are not disease-specific; the substitution of different "disease process" and "damage" measures make them suitable for many rheumatic disorders. The core set is intended to serve as a core for LOS in almost all rheumatic conditions.

Decision Making↗

Linkage of cytokine genes to rheumatoid arthritis. Evidence of genetic heterogeneity.

OBJECTIVE: To investigate linkage of candidate disease susceptibility genes to rheumatoid arthritis (RA) in affected sibling pair families stratified for specific clinical features. METHOD: Two hundred RA affected sibling pair families were genotyped for informative microsatellite markers mapping within or less than 3cM from: INF alpha, INF gamma, INF beta, IL1 alpha, IL1 beta, IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, alpha 1 anti-trypsin, and alpha 1 anti-chymotrypsin, using fluorescence based automated technology. Linkage was examined by defining allele sharing sibling pairs. This was assessed by maximum likelihood-inheritance by descent methods. RESULTS: An increase in allele sharing was seen for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF gamma in sibling pairs with an affected male (LOD 0.96, p = 0.03) and most significantly for IL2 in sibling pairs where one or both were persistently seronegative (LOD 1.05, p = 0.02). CONCLUSION: Weak evidence of linkage of RA to IL5R, IFN gamma, and IL2 has been detected in clinical subsets of sibling pairs suggesting that RA is a genetically heterogeneous disease.

Arthritis, Rheumatoid↗