Investigating the role of the HLA-Cw*06 and HLA-DRB1 genes in susceptibility to psoriatic arthritis: comparison with psoriasis and undifferentiated inflammatory arthritis.

OBJECTIVE: Psoriasis of early onset (type I; age of onset 40 years). HLA-DRB1*07, in linkage disequilibrium with HLA-Cw*06, was also associated with patients with PsA having type I psoriasis (OR 2.7, 95% CI 2.1, 3.7, p<0.00001). HLA-DRB1*04 alleles and the SE were associated with undifferentiated inflammatory arthritis but not with PsA. CONCLUSIONS: The SE is not a PsA susceptibility locus. HLA-Cw*06 and HLA-DRB1*07 are associated with patients with PsA having type I psoriasis, suggesting that the primary association is with age of onset of psoriasis. Patients with PsA having type I psoriasis, therefore, have a genetic background different to those with type II psoriasis, and adjustment for this is necessary in future studies that investigate the genetic susceptibility of PsA.

Ambient noise strategy: a solution for noise control?

The British Government earlier this year undertook a consultation on its proposal, announced in the Rural White Paper, to develop an Ambient Noise Strategy in England. The proposals envisage a three phase approach: In phase 1 we would aim to establish three key sets of information: information on the ambient noise climate in the country--i.e. the number of people affected by different levels of noise, the source of that noise (road, rail, airports and industry) and the location of the people affected, by producing noise maps of the main sources of noise; methods which the Government might use to assess the effects of noise--particularly regarding people's quality of life and tranquility; the techniques available to take action to improve the situation where bad or preserve it where good. In phase 2 we would aim to evaluate and identify options for prioritising the various alternatives from phase 1 in terms not only of costs and benefits but also time-scales and synergies and conflicts with other Government priorities including economic and social issues. An optimal policy reduces noise at lowest net cost, whilst capturing as many synergistic benefits, and minimising any potentially adverse impacts. Decision makers need to ensure that the impacts of the noise policies do not cost society more than the benefits expected. A recent study undertaken by the Government, looked at how a cost-benefit type framework could be used, with noise maps, to help inform such decisions. Finally, in phase 3, the Government would need to agree on the necessary policies to move towards the desired outcome--i.e. the National Ambient Noise Strategy itself. The results of the consultation are expected to be published later this year.

Contribution of patient related differences to multidrug resistance in rheumatoid arthritis.

BACKGROUND: There is a wide variation in responses to standard disease modifying antirheumatic drug (DMARD) treatment in rheumatoid arthritis (RA). Whether multidrug resistance, failure to respond to several DMARDs, is a specific entity over and above that expected by chance alone is unclear. OBJECTIVE: To identify patients with RA who demonstrate a multidrug resistant phenotype and to determine what proportion of the variance in drug responses is due to patient related factors. METHODS: Patients with RA (1987 American College of Rheumatology criteria) were identified from clinics at Manchester Royal Infirmary and through the Arthritis Research Campaign National RA Repository. The clinic records were reviewed and multidrug resistance was defined as stopping three or more DMARDs owing to lack of efficacy after an adequate trial of the drug. Logistic regression measured by a random effects model was used to determine the relative contribution of the drug and subject related differences to the multidrug resistance. RESULTS: 265 patients (210 (79.3%) female) were studied. The mean (SD) age and disease duration were 52.2 (12.9) and 10.7 (8.8) years, respectively. Patients had a median (range) of 2 (1-8) DMARD courses. Failure of at least one DMARD due to inefficacy occurred in 105 (40%) and 13 (5%) were multidrug resistant. Overall, 35% of the variance in drug responses was due to between-subject differences (p=0.02). Rheumatoid factor (RF) status contributed significantly to this (OR=2.15, 95% confidence interval (95% CI) 1.00 to 4.62) but explained only 3% of the total variance in drug inefficacy. CONCLUSION: Multidrug resistance occurs in an uncommon (5%) but important subgroup of patients with RA. The between-subject variance is not fully explained by demographics and RF status. Understanding the biological mechanisms that contribute to multidrug resistance may suggest new therapeutic approaches and targets in RA.