This version is available at https://strathprints.strath.ac.uk/49161/ Strathprints is designed to allow users to access the research output of the University of Strathclyde. Unless otherwise explicitly stated on the manuscript, Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Please check the manuscript for details of any other licences that may have been applied. You may not engage in further distribution of the material for any profitmaking activities or any commercial gain. You may freely distribute both the url (https://strathprints.strath.ac.uk/) and the content of this paper for research or private study, educational, or not-for-profit purposes without prior permission or charge.Any correspondence concerning this service should be sent to the Abstract. : A series of robust iridium(I) complexes bearing a sterically encumbered N-heterocyclic carbene ligand, alongside a phosphine ligand, has been synthesised and investigated in hydrogen isotope exchange processes. These complexes have allowed isotope incorporation over a range of substrates with the use of practically convenient deuterium and tritium gas. Moreover, these active catalysts are capable of isotope incorporation to particularly high levels, whilst employing low catalyst loadings and in short reaction times. In addition to this, these new catalyst species have shown flexible levels of chemoselectivity, which can be altered by simple manipulation of preparative approaches.Furthermore, a number of industrially-relevant drug molecules have also been labelled, including the sulfonamide containing drug, Celecoxib. Alongside detailed NMR experiments, initial mechanistic investigations have also been performed, providing insight into both substrate binding energies, and, more importantly, relative energies of key steps in the mechanistic cycle as part of the overall exchange process.

Practically convenient methods have been developed for the preparation of new iridium complexes, possessing bulky N-heterocyclic carbene and phosphine ligands; these routinely handled complexes are highly active catalysts within directed hydrogen isotope exchange processes.

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The number of patients given DMARD treatment within six months of symptom onset increased from 5% (before 1994) to 44% (1994-7). Seventy three per cent of patients waiting more than a year from symptom onset to first clinic appointment already had erosive change, compared with 34% of patients seen within a year. Conclusions-Patients are being referred earlier in their disease, and DMARDs are prescribed sooner in the disease course. There has been a substantial increase in the proportion of patients treated with a DMARD within six months of symptom onset. (Ann Rheum Dis 1999;58:510-513) The "traditional" pyramid of treatment of rheumatoid arthritis (RA) involved treating patients with non-steroidal anti-inflammatory drugs, before progressing to the use of disease modifying anti-rheumatic drugs (DMARDs) in patients with continuing disease activity. In recent years, this strategy has been rejected, and the early use of DMARDs has been advocated.1 There is some evidence from a randomised trial, that patients experiencing a delay in receiving DMARD treatment develop more functional disability and radiological progression compared with those patients receiving immediate DMARD treatment.2 To identify patients who might benefit from such early intervention, "early synovitis" clinics have been set up. In the past, many patients had already developed established radiological damage at presentation, and it has been hoped that the early identification of RA patients might allow treatment to be started before the development of irreversible joint damage. 3There is evidence from the USA that more patients are being treated with DMARDs, 4 but there has been no published evidence to confirm that patients are referred and treated significantly earlier in their disease course. MethodsThe study was conducted at a single teaching hospital that provides secondary care for patients with rheumatic diseases. Recruitment was of 198 sequential patients seen in the rheumatology clinics for their routine review, over a six week period. All patients fulfilled the American College of Rheumatology criteria for the diagnosis of RA.5 A retrospective case sheet review identified the dates of symptom onset, general practitioner (GP) referral, first clinic appointment, and first use of DMARD. Data were collected on age, sex, erythrocyte sedimentation rate, C reactive protein, rheumatoid factor, and the presence/absence of erosions on hand and foot radiographs at the first clinic assessment. Patients were arbitrarily split into four groups according to the date of their first clinic assessment-before 1986, 1987-9, 1990-3, and 1994-7. Between group comparisons were Group 2 (1986Group 2 ( -1989 Group 3 (1990-1993) (n=52) Group 4 (1994Group 4 ( -1997