Aims In¯ammation reduces hepatic clearance of many drugs with unknown therapeutic consequences. This study was carried out to examine the effect of rheumatoid arthritis (RA) on the pharmacokinetics and pharmacodynamics of verapamil. Methods Eight RA patients were age-and sex-matched with eight healthy volunteers. The disease severity was assessed, and ECG, blood pressure and verapamil enantiomers concentrations were measured for 12 h post 80 mg oral verapamil. Serum interleukin-6 (IL-6) and nitrite (NO 2 ± ) were measured in predose samples. Results IL-6 and NO 2 ± concentrations were signi®cantly increased in parallel with disease severity. Oral clearance of both S-and R-verapamil was signi®cantly decreased by RA. While the unbound fraction of S-and R-verapamil decreased by 5 and 7-fold, respectively, the unbound AUC remained unchanged for the more potent enantiomer, S-verapamil. AUC of norverapamil enantiomers was increased 2±3-fold. Despite elevated serum drug concentrations in RA, the potential to prolong the PR-interval was signi®cantly reduced by one fold and the effect on the heart rate and blood pressure did not increase. Conclusions RA results in increased verapamil concentrations due likely to changes in protein binding, decreased clearance and/or altered hepatic blood¯ow. A signi®cant decrease in dromotropic effect, despite increased serum drug concentrations, may be attributed to receptor down regulation caused by pro-in¯ammatory cytokines and/or NO.

Objective. To determine the safety and efficacy of intravenous (IV) pamidronate treatment in ankylosing spondylitis (AS) patients who have had a suboptimal response to nonsteroidal antiinflammatory drugs (NSAIDs).Methods. Pamidronate at 60 mg was compared with pamidronate at 10 mg rather than placebo in view of the high incidence of transient arthralgias upon first IV exposure to the drug. The drug were given monthly for 6 months in a randomized, double-blind, controlled trial. The inclusion criterion was active disease (Bath AS Disease Activity Index [BASDAI] of >4 or morning stiffness of >45 minutes) despite stable NSAID therapy. The primary outcome measure was the BASDAI, and secondary outcomes included the Bath AS Functional Index (BASFI), Bath AS Global Index (BASGI), Bath AS Metrology Index (BASMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and percentage of patients achieving a reduction of >25% in the BASDAI. Outcome assessments were done at ؊2, 0, 12, and 24 weeks, and analysis was by intent to treat. Results. Eighty-four AS patients (67 men and 17women; mean age 39.6 years and mean disease duration 15.1 years) were enrolled. Dosage groups were well matched at baseline for demographics, disease activity, and functional indices. At 6 months, the mean BASDAI had decreased by 2.22 (34.5%) in the 60-mg group and by 0.93 (15%) in the 10-mg group (P ‫؍‬ 0.002). Significantly greater reductions in the 60-mg group were also noted for the BASFI (P < 0.001), BASGI (P ‫؍‬ 0.01), and BASMI (P ‫؍‬ 0.03). Significantly more patients achieved a reduction of >25% in the BASDAI in the 60-mg group versus the 10-mg group (63.4% versus 30.2%; P ‫؍‬ 0.004). Differences in ESR/CRP were not significant (NS). Withdrawals included 9 (20.9%) from the 10-mg group and 3 (7.3%) from the 60-mg group (P NS). Adverse events were confined to transient arthralgias/ myalgias after the first IV infusion, occurring in 68.3% and 46.5% of patients in the 60-mg and 10-mg groups, respectively (P NS).Conclusion. Pamidronate has dose-dependent therapeutic properties in AS.

Most SF-36 subscales did not adequately reflect changes in the health status of patients with LBP, mostly for those who reported deterioration. Preference-derived quality-of-life scores appeared to discriminate among patients who improved and those who deteriorated, although not as consistently as the disease-specific measure (Oswestry). Additional research is needed to evaluate the role of generic measures of quality of life in the assessment of patients with LBP before they can be widely implemented in clinical settings or outcomes research.

These findings suggest that the communication between physicians and their patients at the time of the medical encounter needs to be enhanced. An understanding of their patients' health perceptions may assist physicians in suggesting appropriate interventions, taking into account their patients' benefit-risk preferences.

Objective. To assess the prevalence, practices, beliefs, and expectations of patients with rheumatic diseases in relation to the use of alternative therapies.Methods. We conducted a cross-sectional survey of 300