-
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. METHODS: Nine new graduates completed the internship programme (July 2006--June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. RESULTS: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. CONCLUSIONS: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales.
Journal of Foot and Ankle Research 04/2013; 6(1):15. · 1.33 Impact Factor
-
Lorraine Southam,
Kalliope Panoutsopoulou,
N William Rayner,
Kay Chapman,
Caroline Durrant,
Teresa Ferreira, Nigel Arden,
Andrew Carr,
Panos Deloukas,
Michael Doherty,
John Loughlin,
Andrew McCaskie,
William E R Ollier,
Stuart Ralston,
Timothy D Spector,
Ana M Valdes,
Gillian A Wallis,
J Mark Wilkinson,
Jonathan Marchini,
Eleftheria Zeggini
[show abstract]
[hide abstract]
ABSTRACT: Imputation is an extremely valuable tool in conducting and synthesising genome-wide association studies (GWASs). Directly typed SNP quality control (QC) is thought to affect imputation quality. It is, therefore, common practise to use quality-controlled (QCed) data as an input for imputing genotypes. This study aims to determine the effect of commonly applied QC steps on imputation outcomes. We performed several iterations of imputing SNPs across chromosome 22 in a dataset consisting of 3177 samples with Illumina 610 k (Illumina, San Diego, CA, USA) GWAS data, applying different QC steps each time. The imputed genotypes were compared with the directly typed genotypes. In addition, we investigated the correlation between alternatively QCed data. We also applied a series of post-imputation QC steps balancing elimination of poorly imputed SNPs and information loss. We found that the difference between the unQCed data and the fully QCed data on imputation outcome was minimal. Our study shows that imputation of common variants is generally very accurate and robust to GWAS QC, which is not a major factor affecting imputation outcome. A minority of common-frequency SNPs with particular properties cannot be accurately imputed regardless of QC stringency. These findings may not generalise to the imputation of low frequency and rare variants.
European journal of human genetics: EJHG 01/2011; 19(5):610-4. · 3.56 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To characterize the long-term mortality in patients with WG compared with matched population-based controls.
We used data from the General Practice Research Database, which contains the computerized records of 6.25 million patients and is representative of the population of the UK. We identified all subjects with a new diagnosis of WG in the period 1989-2004, and for each case, compared mortality with 10 controls matched for age, gender and practice.
We identified 255 patients with a new diagnosis of WG (mean age 58.1 years, range 9-90 years, 47% females) and 2546 controls (mean age 58.1 years, range 9-89 years, 47% females). Mean follow-up was 6.4 years. The mortality for patients with WG was significantly increased during the first year after diagnosis [HR 9.0 (95% CI 5.8, 13.9)], especially for those ≤ 65 years of age [HR 19.9 (95% CI 8.8, 44.9)]. The excess mortality was less marked after the first year: 1-5 years [HR 1.68 (95% CI 1.08, 2.60)], 5-10 years [HR 2.41 (95% CI 1.43, 4.07)], but started to increase by 10-15 years [HR 4.4 (95% CI 2.0, 9.8)]. The Kaplan-Meier survival curve showed an increase in mortality after 8 years.
Despite current therapy, patients with WG have a 9-fold increased risk of death in the first year of disease, attributed to infection, active vasculitis and renal failure. Between 1 and 8 years the risk is at its lowest, although higher than the control population. There is an increased mortality from 8 years onwards that remains unexplained.
Rheumatology (Oxford, England) 11/2010; 50(4):697-702. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To test the hypothesis that interventions targeting the relief of pain and disability in musculoskeletal diseases may have differential effects on activity limitation and participation restriction as defined in the International Classification of Functioning, Disability and Health (ICF).
Full data were obtained for 3 randomized controlled trials that used the Western Ontario and McMaster Universities Osteoarthritis Measure (WOMAC), the Medical Outcomes Study Short-form 36 (SF-36), or the Oswestry Disability Questionnaire as their primary outcome measures. The trial outcomes were reanalyzed using items previously designated as assessing pure activity limitation (A) or participation restriction (P), or a mixture of the 2 (A/P) only, and the results compared with the outcomes found using the full scales, which assess a mixture of outcome domains.
The results did not refute the hypothesis. An exercise-based intervention and injection therapies both appeared to have more effect on participation restriction (P) than on activity limitation (A), while a drug-based intervention had more effect on A than on P.
Different interventions used to treat musculoskeletal disorders may have differential effects on impairment, activity limitation, and restricted participation. The use of outcome measures that do not differentiate these 3 domains may obscure the true value of an intervention.
The Journal of Rheumatology 09/2010; 37(9):1923-31. · 3.69 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Abstract
Background
Inhibition of tumour necrosis factor ( TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability.
Methods
Consecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2<sup>nd </sup>and 5<sup>th </sup>metatarso-phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI).
Results
31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p < 0.001), C-reactive protein (t = 3.889, p = 0.001), 28 joint Disease Activity Score (t = 3.712, p = 0.0001), Visual Analog Scale (t = 2.735, p = 0.011) and Manchester Foot Pain and Disability Index (t = 3.712, p = 0.001).
Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant.
Conclusions
Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.
Journal of Foot and Ankle Research. 01/2010;
-
[show abstract]
[hide abstract]
ABSTRACT: Osteoarthritis (OA) is the most common joint disorder in the world. In Western populations it is one of the most frequent causes of pain, loss of function and disability in adults. Radiographic evidence of OA occurs in the majority of people by 65 years of age and in about 80% of those aged over 75 years. In the US it is second only to ischaemic heart disease as a cause of work disability in men over 50 years of age, and accounts for more hospitalizations than rheumatoid arthritis (RA) each year. Despite this public health impact, OA remains an enigmatic condition to the epidemiologist. In this chapter, we will review the definition and classification of OA, its prevalence, incidence, risk factors and natural history.
Bailliè re s Best Practice and Research in Clinical Rheumatology 03/2006; 20(1):3-25. · 2.65 Impact Factor
-
