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  • Designer hips.

    3 July 2018

  • Cell proliferation is a key determinant of the outcome of FOXO3a activation.

    3 July 2018

    The FOXO family of forkhead transcription factors have a pivotal role in determining cell fate in response to oxidative stress. FOXO activity can either promote cell survival or induce cell death. Increased FOXO-mediated cell death has been implicated in the pathogenesis of degenerative diseases affecting musculoskeletal tissues. The aim of this study was to determine the conditions under which one member of the FOXO family, FOXO3a, promotes cell survival as opposed to cell death. Treatment of primary human tenocytes with 1 pM hydrogen peroxide for 18 h resulted in increased protein levels of FOXO3a. In peroxide-treated cells cultured in low serum media, FOXO3a inhibited cell proliferation and protected against apoptosis. However in peroxide treated cells cultured in high serum media, cell proliferation was unchanged but level of apoptosis significantly increased. Similarly, in tenocytes transduced to over-express FOXO3a, cell proliferation was inhibited and level of apoptosis unchanged in cells cultured in low serum. However there was a robust increase in cell death in FOXO3a-expressing cells cultured in high serum. Inhibition of cell proliferation in either peroxide-treated or FOXO3a-expressing cells cultured in high serum protected against apoptosis induction. Conversely, addition of a Chk2 inhibitor to peroxide-treated or FOXO3a-expressing cells overrode the inhibitory effect of FOXO3a on cell proliferation and led to increased apoptosis in cells cultured in low serum. This study demonstrates that proliferating cells may be particularly susceptible to the apoptosis-inducing actions of FOXO3a. Inhibition of cell proliferation by FOXO3a may be a critical event in allowing the pro-survival rather than the pro-apoptotic activity of FOXO3a to prevail.

  • Orthopaedic trial networks.

    3 July 2018

    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 July 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.

    3 July 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.

    3 July 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.