Elicitation of health state utilities associated with differing durations of morning stiffness in rheumatoid arthritis.

OBJECTIVE: Specific symptoms of rheumatoid arthritis (RA), including joint stiffness and functional disability, are most severe in the morning. 'Morning stiffness' has a negative impact on health-related quality-of-life (HRQoL); however, how HRQoL is correlated to morning stiffness duration is unknown. The objective of this study was to obtain population-based utility values associated with different durations of morning stiffness in RA. DESIGN AND METHODS: The time-trade-off (TTO) approach was used to elicit utility values for four different health states (HS), which differed in morning stiffness duration. One hundred and nine members of the UK general public rated each HS in individual face-to-face interviews with trained investigators. TTO scores were converted into utility values. Visual Analog Scale (VAS) scores were obtained to validate TTO scores. RESULTS: On a scale of 0 (death) to 1 (full health), a mean utility value of 0.45±0.29 was elicited for ∼3 h of morning stiffness (anchor HS), 0.50±0.28 for 2-3 h of morning stiffness (HS1), 0.61±0.25 for 1-2 h of morning stiffness (HS2) and 0.78±0.20 for <1 h of morning stiffness (HS3). The difference between each HS was statistically significant (p<0.01). Mean VAS utility scores followed the same trend. Utility incrementally increased with each HS associated with a shorter duration of morning stiffness. Limitations of this research include potential bias from the TTO method due to the discounting effect of time, scale compatibility, and loss aversion. CONCLUSIONS: The UK population-based utility values show a reduction in morning stiffness duration in RA is associated with improved HRQoL. Despite the impact of morning stiffness on HRQoL, it is rarely evaluated and little is known as to how it is affected by current treatments. The results of this study can be applied in future cost-utility analyses of healthcare interventions which target an improvement in morning stiffness duration for RA patients.

Expression of a novel splice variant of human mGluR1 in the cerebellum.

We have isolated clones of a novel splice variant of metabotropic glutamate receptor type 1 (mGluR1) from a human cerebellum cDNA library. Translation of this variant, mGluR1g would result in the addition of just one amino acid after the exon/intron boundary where the other splice variants diverge. RNA dot blot analysis using an mGluR1g-specific probe demonstrated expression in the cerebellum and also high levels in the kidney. Northern blotting using the same probe showed expression of a 4 kb transcript in the cerebellum. In situ hybridization studies in the cerebellum showed that mGluR1g mRNA is only expressed in granule cells, compared with mGluR1a/b mRNA which is also found in Purkinje cells and basket cells. Transcripts of the analogous splice variant are also present in rat brain mRNA.

Human metabotropic glutamate receptor type 7: molecular cloning and mRNA distribution in the CNS.

Human metabotropic glutamate receptor type 7 (mGluR7) cDNA clones were isolated from a medulla cDNA library. The sequence, which includes a polymorphism, has 92% DNA sequence identity with rat mGluR7 and the predicted protein sequence has 99% identity. In-situ hybridization studies on human brain sections showed that mGluR7 mRNA has a widespread distribution with highest levels in the hippocampal formation, cerebral cortex and cerebellum.