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  • Orthopaedic trial networks.

    12 December 2017

    Randomized controlled trials (RCTs) are considered the most robust design for evaluating health care interventions. However, it is difficult to acquire funding for RCTs, and they are complex to set up. Threats to their successful conduct and impact on clinical practice, particularly in surgical trials, include problems with recruitment, notably in terms of clinical equipoise and patient acceptability. Historically, RCTs are less common in surgical specialties, and their contribution to the orthopaedic literature remains small. Orthopaedic networks, such as orthopaedic associations, specialist societies, travel fellowships, and clinical research networks, provide an opportunity to meet the challenges of promoting RCTs in orthopaedic clinical practice. This can include identifying important research questions to help prioritize funding; educating and training surgeons in the design and practice of RCTs; helping to promote and coordinate RCTs; and disseminating the findings of RCTs. Orthopaedic trial networks should be encouraged to promote a research culture in which RCTs are feasible and to ensure that scarce resources utilized to support their funding are used most efficiently and to best effect. In particular, the use of networks is encouraged to support the conduct of RCTs in achieving patient recruitment, which is crucial in providing the evidence base to inform orthopaedic practice. Furthermore, to improve generalizability, acceptance of study findings and communication between orthopaedic surgeons, as well as international collaboration in trials, should be part of the strategy for the future.

  • Review of clinical outcomes-based anchors of minimum clinically important differences in hip and knee registry-based reports and publications.

    3 April 2018

    Patient-reported outcome measures are tools that allow clinicians and researchers to gauge patients' level of satisfaction and quality of life after a medical intervention. The use of patient-reported outcome measures and the clinically relevant score differentials over time as they relate to outcomes (minimum clinically important differences) has been proposed as a way to understand success and failure rates in orthopaedics. We conducted a systematic appraisal of literature in peer-reviewed journals and registry reports to measure the use that registries and other large data repositories make of minimum clinically important differences and to understand methodological approaches for such uses. Of the nineteen registry reports and 1052 articles examined, we found that only one report and two studies mentioned the use of patient-reported outcome measures and minimum clinically important differences in the context of revision rates of total knee arthroplasty and total hip arthroplasty. We conclude that although the infrastructure and efforts to routinely collect patient-reported outcome measures at registry levels do exist, there is limited use of minimum clinically important differences to understand and potentially predict clinical outcomes. We suggest advancing the global infrastructure such as the International Consortium of Orthopaedic Registries to address how research related to patient-reported outcome measures can help individual registries collaborate in the development of tools and allow aggregation of data.

  • Comparison of clinical and patient-based measures to assess medium-term outcomes following shoulder surgery for disorders of the rotator cuff.

    20 March 2018

    OBJECTIVE: To compare different assessments following shoulder surgery for impingement syndrome with or without rotator cuff tear or repair. METHODS: A prospective study of 93 patients was conducted. Standard assessments were performed before, at 6 months, and at 4 years following shoulder surgery using the patient-based Oxford Shoulder Score (OSS), the Medical Outcomes Study Short Form-36 (SF-36) questionnaire, and a surgeon-assessed Constant Shoulder Score. Patients were categorized according to the surgery received in relation to the presence of cuff tears: full repair, partial repair, cuff tear/no repair, no tear/no repair. RESULTS: Most patients (57%) received subacromial decompression for impingement with no cuff tear. This group had the fewest pre- and postoperative symptoms. The category of patients who received only partial repair of a cuff tear had worse scores on all outcome assessments compared with other groups. Patient-based measures were more stable over time than the Constant. CONCLUSION: The shoulder-specific measures had greater sensitivity than the SF-36 in registering significant differences in outcomes between comparison groups at 6 months and 4 years.

  • Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients.

    28 March 2018

    OBJECTIVE: The groin pain experienced by patients with hip osteoarthritis (OA) is often accompanied by areas of referred pain and changes in skin sensitivity. We aimed to identify the supraspinal influences that underlie these clinical manifestations that we consider indicative of possible central sensitization. METHODS: Twenty patients with hip OA awaiting joint replacement and displaying signs of referred pain were recruited into the study, together with age-matched controls. All subjects completed pain psychology questionnaires and underwent quantitative sensory testing (QST) in their area of referred pain. Twelve of 20 patients and their age- and sex-matched controls underwent functional magnetic resonance imaging (MRI) while the areas of referred pain were stimulated using cold stimuli (12 degrees C) and punctate stimuli (256 mN). The remaining 8 of 20 patients underwent punctate stimulation only. RESULTS: Patients were found to have significantly lower threshold perception to punctate stimuli and were hyperalgesic to the noxious punctate stimulus in their areas of referred pain. Functional brain imaging illustrated significantly greater activation in the brainstem of OA patients in response to punctate stimulation of their referred pain areas compared with healthy controls, and the magnitude of this activation positively correlated with the extent of neuropathic-like elements to the patient's pain, as indicated by the PainDETECT score. DISCUSSION: Using psychophysical (QST) and brain imaging methods (functional MRI), we have identified increased activity with the periaqueductal grey matter associated with stimulation of the skin in referred pain areas of patients with hip OA. This offers a central target for analgesia aimed at improving the treatment of this largely peripheral disease.

  • Impact of persistent hip or knee pain on overall health status in elderly people: a longitudinal population study.

    21 February 2018

    OBJECTIVE: To investigate hip or knee symptoms in older persons from a longitudinal, population perspective, and to determine the impact of persistent hip or knee pain on general health status over time. METHODS: A postal questionnaire was sent to a random sample of 5,500 individuals ages > or = 65 years containing the Short Form 36 (SF-36) general health survey, Lequesne hip and knee indices, and a hip/knee pain severity item. Respondents reporting hip or knee symptoms at baseline received an identical questionnaire 12 months later. Respondents were classified into a persistent pain group with either hip or knee pain at both baseline and followup, and a non-persistent pain group who reported hip or knee pain at baseline but no pain at followup. RESULTS: At baseline, 1,305 (40.7%) of 3,210 eligible respondents reported hip or knee pain. At 1 year, 1,072 (82.1%) of 1,305 individuals responded, of whom 820 (76.5%) remained symptomatic (the persistent group). In multivariate analysis, baseline factors identified as strongly related to having persistent pain were maximum Lequesne score (odds ratio [OR] 1.09, P < 0.001), maximum hip/knee pain score (OR 1.61, P < 0.001), and number of painful hip and knee joints at baseline (OR 1.48, P = 0.004). Following adjustment for age, sex, and baseline score, differences in mean SF-36 change scores of the 2 groups were significant for all dimensions except for mental health. CONCLUSION: In older persons, a symptomatic hip or knee frequently progresses in terms of worsening symptoms and accrual of other symptomatic hip or knee joints. The impact of persistent symptoms on general health is substantial.

  • Large replication study and meta-analyses of DVWA as an osteoarthritis susceptibility locus in European and Asian populations.

    3 April 2018

    Recently, through a genome wide association study in Japanese knee osteoarthritis (OA) cases, a previously unknown gene, DVWA, was identified. The non-synonymous single nucleotide polymorphism (SNP) rs7639618 was subsequently found to be consistent and most significantly associated in Japanese and Han Chinese knee OA studies and functional relevant. Here, the association of the DVWA polymorphisms (rs7639618, rs11718863 and rs9864422) was genotyped in 1120 knee OA cases, 1482 hip OA cases and 2147 controls, all of white European descent from the Netherlands, the UK, Spain and Greece. Random effect DerSimonian and Laird meta-analyses were performed to assess the association in the different strata. To assess a more global effect, the original Japanese and Chinese data were included with the European. The meta-analyses provided evidence for global association of rs7639618 with knee OA with an odds ratio (OR) of 1.29, 95% confidence interval (CI) of 1.15-1.45 and a P-value of 2.70 x 10(-5). This effect, however, showed moderate heterogeneity, and rs7639618 was not independently associated with knee OA in Europeans, with an OR of 1.16, 95% CI of 0.99-1.35 and a P-value of 0.063. Furthermore, no association was observed with hip OA in Europeans, with a P-value of 0.851. Our results suggest that there may be global relevance for the DVWA SNP rs7639618 among knee OA cases, however, the apparent lower effect size in combination with the higher risk allele frequency in the European samples highlights again the ethnic differences in effects of discovered OA susceptibility genes.

  • Shoulder pain.

    26 February 2018

  • Watt Group | Translational Research in Osteoarthritis

    18 December 2017

    Our group tests findings from the laboratory in human clinical studies, and runs experimental medicine studies and clinical trials relevant to osteoarthritis within the Arthritis Research UK Centre for Osteoarthritis Pathogenesis.

  • Midwood Group | Matrix Immunology

    23 October 2017

    Our group investigates how the extracellular matrix - the component of tissue that lies immediately outside and between cells - contributes to inflammation.

  • Powrie Group | Mucosal Immunology

    17 April 2018

    Work in the Powrie lab is focused on understanding the interaction between the intestinal microbiota and the host immune system and how this mutualistic relationship breaks down in inflammatory bowel disease and cancer.

  • Arnon Group | Humoral Immune Response

    23 October 2017

    The main focus of the lab is to understand how humoral immune responses are regulated within the spleen.

  • Wann Group | Primary Cilia in Inflammatory Signalling

    23 October 2017

    Cells use unique spaces to organise the messaging that modifies their behaviour and respond to their environment. Our research looks at how one such space - the primary cilium - affects the way cells respond to inflammation.

  • Udalova Group | Genomics of Inflammation

    17 January 2018

    Work in the Udalova is focused on understanding how the inflammatory response is controlled on the molecular level.

  • Griseri Group | Haematopoiesis and Chronic Inflammation

    23 October 2017

    Can we treat chronic inflammatory arthritis by modulating the abnormal activity of the immune system factory - the bone marrow - to weaken the excessive accumulation of tissue-destructive white blood cells in the joints?

  • Research Informatics

    23 October 2017

    We are responsible for providing the Institute with solutions to challenges associated with the wide diversity of data generated and used by our scientists.

  • Venables Group | Citrullination in Inflammation

    23 October 2017

    Our main focus is to discover the causes of Rheumatoid Arthritis and contribute to the strategies for prevention and cure of this condition.