My main research interests are osteoarthritis (OA) and crystal arthritis (gout and calcium pyrophosphate crystal deposition (CPPD)), evidence-based medicine and development of evidence-based clinical guidelines for diagnosis and management of OA and crystal arthritis. This involves, epidemiological studies, identification of risk factors (including genetic associations), systematic reviews and meta-analyses, clinical observational studies and community-based randomised controlled trials (RCTs). Current studies include:
(1) the Genetics of OA and Lifestyle (GOAL) study. This large database contains information on over 3,000 well-characterised participants with either knee OA, hip OA, or no large joint OA (controls). We have used the database to identify risk factors for knee and hip OA and currently are examining: gene-environmental interaction between TGF and obesity in knee and hip OA; the correlation between finger interphalangeal nodes and underlying radiographic OA; differening radiographic phenotypes of OA according to presence of CPPD; morphological risk factors for hip OA; and different radiographic patterns of hip OA according to presence of finger nodes and OA.
(2) identification of novel genetic associations for knee and hip OA as a key collaborating centre in the ARCoGen (Arthritis Research UK (ARUK) funded) and TreatOA consortia.
(3) the ARUK Gout Trial - a community-based RCT comparing nurse-led management of gout (reflecting current recommended best practice) and standard (GP led) care over 2 years.
(4) the "HERO" UK multi-centre study (ARUK funded) examining efficacy of hydroxychloroquine in people with symptomatic hand OA.
(5) the Nottingham Biomarker Study, in collaboration with Professors Victoria Chapman and David Barrett, which is examining differences in knee synovial fluids on mass spectroscopy between people with knee OA and those with normal knees.
(6) systematic reviews and meta-analyses comparing the placebo response in 2 contrasting chronic painful conditions - fibromyalgia (predominantly caused by central pain sensitisation) and OA (predominantly caused by peripheral tissue damage).
(7) comparison of incidence, prevalence, risk factors and outcomes of gout in the UK (using the UK GP Research Database) and Taiwan (using a nation-wide national database). We have already identified strong familial risk of gout in Taiwan, especially in women (even though gout predominates in men).
Arthritis Research UK Pain Centre
Academic Rheumatology is the administrative centre for the newly established ARC Pain Centre in Nottingham. The Director of the Pain Centre is Dr David Walsh and details can be found on its dedicated website: http://www.nottingham.ac.uk/paincentre
Recently completed research includes:
(1) a qualitative study of gout patients, general practitioners, practice nurses and hospital doctors to determine illness perceptions and possible barriers to the management of gout (Phase 1 of the ARUK Gout Trial) (submitted for publication)
(2) a 3 month RCT comparing the efficacy and safety of paracetamol, ibuprofen or the combination of the two (in over-the-counter doses) in people with knee pain/OA. The results showed better efficacy from the combination, supporting the concept of additive analgesia for pain control, but a higher incidence of (presumed) gut-related bleeding. This is the first study to demonstrate drops in haemoglobin due to paracetamol, comparable to those due to ibuprofen.
(3) identification of new risk factors for knee OA (index:ring finger or 2D:4D ratio), hip OA (non-spherical femoral head, neck-shaft angle, mild acetabular dysplasia) and CPPD at the knee (self-reported early life constitutional varus malalignment) using the GOAL database
(4) demonstration of a negative association between pain persistence post knee or hip total joint replacement for OA and severity of pre-operative radiographic OA - suggesting that constitutional pain threshold and central sensitisation may be relevant to outcome of large joint OA and its treatment
(5) confirmation of new genetic markers for knee and hip OA, including GDF5, TRPV1, PTGS2 (cyclooxygenase-2 gene), and MCF2L HLA Class II/ BTNL2
(6) a retrospective cohort study documenting the incidence of knee pain in the community and estimation of risk prediction models for knee OA
(7) systematic reviews and meta-analyses showing that: smoking is not negatively associated ("protective") with knee OA and that injury, occupational activity and obesity are risk factors for knee OA
(8) publication of European (EULAR) evidence-based recommendations for diagnosis and management of CPPD and for diagnosis of knee OA
Currently we are developing 2 RCTs in knee OA for possible funding by ARUK:
(1) an RCT to examine clinical predictors of response (e.g. pain pattern at the knee, pain elsewhere, ultrasound assessed knee synovitis) to paracetamol, naproxen and placebo in people with knee OA using a within-patient cross-over design.
(2) an RCT to compare the magnitude of improvement in symptoms when the contextual response to treatment is maximised.
(3) study of metabonomic markers for knee and hip OA using the GOAL database
(4) study of genetics of people with crystal proven gout as part of European Crystal Network