Disease activity, smoking, and reproductive-related predictors of poor prognosis in patients with very early inflammatory polyarthritis.

OBJECTIVE: To identify disease activity, smoking, and reproductive-related predictors of a poor prognosis in patients with very early inflammatory polyarthritis (IP). METHODS: Patients with very early IP (symptom duration 4-11 weeks) included in our study were participants in the STIVEA (Steroids In Very Early Arthritis) randomized placebo-controlled trial. At baseline, disease-related variables were measured and patients were asked to complete a questionnaire covering smoking status and reproductive questions. Baseline predictors of poor prognosis [i.e., the need to start disease-modifying antirheumatic drug (DMARD) therapy by 6 months or the clinical diagnosis of rheumatoid arthritis (RA) at 12 months] were identified, applying logistic regression analyses adjusted for treatment group. RESULTS: Rheumatoid factor (RF) positivity was one of the strongest clinical predictors of a poor prognosis: OR for DMARD therapy at 6 months, 4.00 (95% CI 2.00-8.00) and OR for a diagnosis of RA at 12 months, 9.48 (95% CI 4.48-20.07). There was a significant association between current smoking at baseline compared to never smoking and a diagnosis of RA at 12 months (OR 3.15, 95% CI 1.16-8.56). CONCLUSION: About 6 in 7 patients with very early RF-positive IP were diagnosed with RA 1 year later. In addition, 1 in 4 IP patients who smoke will develop RA later. It is recommended to treat RF-positive patients who have IP with DMARD at presentation and to advise patients to stop smoking.

Effect of psychological distress on continuation of anti-tumor necrosis factor therapy in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship of psychological distress and associated factors with continuation of tumor necrosis factor (TNF) antagonist therapy in patients with rheumatoid arthritis (RA). METHODS: Patients about to start therapy with TNF antagonists (n = 166) were assessed for psychological distress using the Hospital Anxiety and Depression Scale (HADS). A core set of demographic and clinical variables, including comorbidities from medical records and cigarette smoking history by questionnaire, were recorded at baseline and regular intervals thereafter. Cox proportional hazards regression analysis was used to assess the likelihood of patients discontinuing therapy over a 36-month followup period. RESULTS: The number of years smoked was associated with anxiety (HADS-A; p for trend = 0.008) and general psychological distress (HADS-Total; p for trend = 0.03). In univariate analyses, earlier discontinuation was associated with these variables at baseline: anxiety (HADS-A), depression (HADS-D), abnormal mood (HADS-Total), smoking history (> 30 pack-yrs), years smoked (> 30 yrs), current smoking, high Disease Activity Score 28-joint count (DAS28), poor patient global assessment, and evidence of cardio/cerebrovascular disease (CVD). In multivariate analyses, the strongest predictors of discontinuation were HADS-Total, smoking history (> 30 pack-yrs), DAS28, and evidence of CVD at baseline. CONCLUSION: Discontinuation of therapy with TNF antagonists is independently associated with psychological distress, heavy smoking, and CVD at baseline.

Anemia in rheumatoid arthritis: association with polymorphism in the tumor necrosis factor receptor I and II genes.

OBJECTIVE: To investigate whether polymorphisms in the tumor necrosis factor receptor I (TNFRSF1A) and receptor II (TNFRSF1B) genes are associated with the anemia observed in rheumatoid arthritis (RA). METHODS: We studied a group of Caucasian patients (n = 160) with established RA on whom longitudinal data of hemoglobin (Hb) levels over 5 years were recorded. A second group of patients (n = 102) with early RA was used for a confirmation study. Polymerase chain reaction restriction fragment length polymorphism analysis was used to genotype patients for the A36G polymorphism in the TNFRSF1A gene, and the T676G polymorphism in TNFRSF1B. Serum levels of ferritin were determined by ELISA and used to differentiate between iron deficiency anemia (IDA) and anemia of chronic disease (ACD). Data were analyzed by Kruskal-Wallis analysis of variance and logistic regression analysis. RESULTS: The TNFRSF1A GG genotype was associated with lower 5-year mean area under the curve Hb levels compared with other genotypes (p = 0.01). Analysis of anemic status showed an increased frequency of anemia in patients carrying a G allele, with the highest frequency in GG homozygotes. The TNFRSF1A GG genotype was significantly associated with IDA in established RA (OR 4.3, p = 0.01), and this was confirmed in a group of patients with early RA (OR 4.8, p = 0.04). Analysis of the combined groups also showed a weak association of the G allele with ACD (OR 2.2, p = 0.04). No association was found between TNFRSF1B variants and anemia when the cohorts were analyzed separately, but an association between carriage of the T allele and ACD was found when the 2 groups were combined (OR 11.5, p = 0.01). CONCLUSION: Our data suggest that polymorphisms within the TNFRSF1A and TNFRSF1B genes are associated with IDA and/or ACD in patients with RA.

GPs' perceptions of the role of DEXA scanning: an exploratory study.

BACKGROUND: Current recommendation are that women with clinical indicators of low bone mineral density should be offered a DEXA (dual energy X-ray absorptiometer) scan to help assess the need for treatment, but little is known about GPs' attitudes towards DEXA scans. OBJECTIVE: Our aim was to explore GPs' beliefs about diagnosis and management of osteoporosis, including the role that DEXA scanning can play. METHODS: Semi-structured interviews with five GPs in the North Staffordshire area were used to explore how GPs make decisions about diagnosis and treatment of osteoporosis, including the use of scans and the application of potential clinical risk factors to decisions about screening and treatment. RESULTS: The decision-making process about whether and who to scan is complex and was influenced by a range of factors including issues of diagnosis, treatment, patient pressure and 'external' factors such as practice protocol and the perceived local availability of scans. CONCLUSIONS: GPs found it difficult to decide who and when to scan despite guidelines for primary care. Perceived local availability of DEXA scans is important and has implications for raising awareness.

No association of polymorphisms in the tumor necrosis factor receptor I and receptor II genes with disease severity in rheumatoid arthritis.

OBJECTIVE: A recent Italian study found that homozygosity for the G allele of the +196 single nucleotide polymorphism (SNP) of the tumor necrosis factor receptor II (TNFRSF1B) gene was more prevalent in patients with severe rheumatoid arthritis (RA). We investigated whether this particular SNP, and also one at position +36 in exon 1 of the TNF receptor I (TNFRSF1A) gene, are associated with disease severity. METHODS: A group of 181 Caucasian patients with RA was studied. DNA was isolated from patient blood samples and subsequently used to genotype both the exon 1 TNFRSF1A SNP and the exon 6 TNFRSF1B SNP by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Radiographic damage was measured by the Larsen score, and functional outcome was assessed by the Health Assessment Questionnaire (HAQ). Data were analyzed by multiple regression analysis, with correction for age, sex, and disease duration. RESULTS: The mean Larsen and HAQ scores did not differ significantly between each of the genotypes from the 2 TNFR SNP. No significant associations between the +36 TNFRSF1A SNP or the +196 TNFRSF1B SNP genotypes and disease severity were found after correcting for age, sex, and disease duration. CONCLUSION: Our data suggest that neither the +36 TNFRSF1A SNP nor the +196 TNFRSF1B SNP is associated with RA severity in a population of Caucasian patients with RA.

Osteoporosis: what are the implications of DEXA scanning 'high risk' women in primary care?

BACKGROUND: Current recommended practice for the use of dual X-ray absorptiometry (DEXA) scans in screening for osteoporosis is to concentrate on women at 'high risk'. OBJECTIVE: We have applied such a screening strategy, in a general practice setting, to estimate the number of women requiring scans. METHODS: A two-phase survey was carried out: (i). postal screen of clinical indicators for low bone mineral density (BMD) to define women at 'high risk'; and (ii). DEXA scanning of the sample at 'high risk' set in two general practices in North Staffordshire. Computerized general practice records were used to define a purposive sample of 1001 women, to receive the screening tool, consisting of three equal size groups (i). those with an early hysterectomy; (ii). those receiving oral corticosteroids on repeat prescription; and (iii). those on the practice cervical smear register. A random sample of women defined at 'high risk' by the screening tool were invited to have a DEXA scan. The main outcome of interest was the presence of low BMD as measured by a DEXA scanner. RESULTS: Sixty-five out of 95 women invited (68%) agreed to undergo a DEXA scan: median age = 52 years (interquartile range 44-64 years). Twenty-nine of these 65 women (45%) were classified with low BMD (WHO criteria): 90% had densities below their age-matched mean. Extrapolating from the observed findings to the main study practice (n = 9000 total population), we estimate that 162 women would be defined at 'high risk', and, if all were offered a scan, 105 would comply and 56 would be defined with low BMD. CONCLUSIONS: Using this approach, we estimate the unmet need, in women, for DEXA scans to be 180 per 10000 total practice population. Allowing for scan uptake, this would define approximately 60 women per 10000 total practice population with low BMD. The application of this screening strategy has identified a group of women who might benefit from treatment or prophylaxis for osteoporosis.

"I'd rather go and know": women's understanding and experience of DEXA scanning for osteoporosis.

OBJECTIVE: To explore women's knowledge and understanding of osteoporosis and of dual energy x-ray absorptiometer (DEXA) scans; the factors influencing their decision to have a scan and their experience of undergoing a DEXA scan. DESIGN: In-depth interviews (using a topic guide) were carried out with 12 women [before a DEXA scan and after they had discussed the results with their general practitioner (GP)] and with three women who chose not to have a scan. SETTING: Stoke-on-Trent, Staffordshire, UK. PARTICIPANTS: Women who responded to a primary-care based questionnaire were purposively selected for interview. RESULTS: The women interviewed had varied levels of understanding of osteoporosis. For the majority of participants the scan was an overwhelmingly positive experience, despite some women's negative expectations. Findings are also explored in terms of the influences on women's decision-making about whether to have a scan and the concept of "knowing" one's risk status. CONCLUSIONS: The main implication for primary care is how to improve women's understanding of osteoporosis and DEXA scans in order to promote the strategy of scanning high-risk women.