The Achilles tendon total rupture score : a study of responsiveness, internal consistency and convergent validity on patients with acute Achilles tendon ruptures

Background The Achilles tendon Total Rupture Score was developed by a research group in 2007 in response to the need for a patient reported outcome measure for this patient population. Beyond this original development paper, no further validation studies have been published. Consequently the purpose of this study was to evaluate internal consistency, convergent validity and responsiveness of this newly developed patient reported outcome measure within patients who have sustained an isolated acute Achilles tendon rupture. Methods Sixty-four eligible patients with an acute rupture of their Achilles tendon completed the Achilles tendon Total Rupture Score alongside two further patient reported outcome measures (Disability Rating Index and EQ 5D). These were completed at baseline, six weeks, three months, six months and nine months post injury. The Achilles tendon Total Rupture Score was evaluated for internal consistency, using Cronbach's alpha, convergent validity, through correlation analysis and responsiveness, by analysing floor and ceiling effects and calculating its relative efficiency in comparison to the Disability Rating Index and EQ 5D scores. Results The Achilles tendon Total Rupture Score demonstrated high internal consistency (Cronbachs alpha > 0.8) and correlated significantly (p < 0.001) with the Disability Rating Index at five time points (pre-injury, six weeks, three, six and nine months) with correlation coefficients between -0.5 and -0.9. However, the confidence intervals were wide. Furthermore, the ability of the new score to detect clinically important changes over time (responsiveness) was shown to be greater than the Disability Rating Index and EQ 5D. Conclusions A universally accepted outcome measure is imperative to allow comparisons to be made across practice. This is the first study to evaluate aspects of validity of this newly developed outcome measure, outside of the developing centre. The ATRS demonstrated high internal consistency and responsiveness, with limited convergent validity. This research provides further support for the use of this outcome measure, however further research is required to advocate its universal use in patients with acute Achilles tendon ruptures. Such areas include inter-rater reliability and research to determine the minimally clinically important difference between scores

Injection therapies for Achilles tendinopathy

Background: Achilles tendinopathy is a common condition, often with significant functional consequences. As a wide range of injection treatments are available, a review of randomised trials evaluating injection therapies to help inform treatment decisions is warranted. Objectives: To assess the effects (benefits and harms) of injection therapies for people with Achilles tendinopathy. Search methods: We searched the following databases up to 20 April 2015: the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, CINAHL and SPORTDiscus. We also searched trial registers (29 May 2014) and reference lists of articles to identify additional studies. Selection criteria: We included randomised and quasi-randomised controlled trials evaluating injection therapies in adults with an investigator-reported diagnosis of Achilles tendinopathy. We accepted comparison arms of placebo (sham) or no injection control, or other active treatment (such as physiotherapy, pharmaceuticals or surgery). Our primary outcomes were function, using measures such as the VISA-A (Victorian Institute of Sport Assessment-Achilles questionnaire), and adverse events. Data collection and analysis: Two review authors independently extracted data from the included studies. We assessed treatment effects using mean differences (MDs) and 95% confidence intervals (CIs) for continuous variables and risk ratios (RRs) and 95% CIs for dichotomous variables. For follow-up data, we defined short-term as up to six weeks, medium-term as up to three months and longer-term as data beyond three months. We performed meta-analysis where appropriate. Main results: We included 18 studies (732 participants). Seven trials exclusively studied athletic populations. The mean ages of the participants in the individual trials ranged from 20 years to 50 years. Fifteen trials compared an injection therapy with a placebo injection or no injection control, four trials compared an injection therapy with active treatment, and one compared two different concentrations of the same injection. Thus no trials compared different injection therapies. Two studies had three trial arms and we included them twice in two different categories. Within these categories, we further subdivided injection therapies by mode of action (injury-causing versus direct repair agents). The risk of bias was unclear (due to poor reporting) or high in six trials published between 1987 and 1994. Improved methodology and reporting for the subsequent trials published between 2004 and 2013 meant that these were at less risk of bias. Given the very low quality evidence available from each of four small trials comparing different combinations of injection therapy versus active treatment and the single trial comparing two doses of one injection therapy, only the results of the first comparison (injection therapy versus control) are presented. There is low quality evidence of a lack of significant or clinically important differences in VISA-A scores (0 to 100: best function) between injection therapy and control groups at six weeks (MD 0.79, 95% CI -4.56 to 6.14; 200 participants, five trials), three months (MD -0.94, 95% CI -6.34 to 4.46; 189 participants, five trials) or between six and 12 months (MD 0.14, 95% CI -6.54 to 6.82; 132 participants, three trials). Very low quality evidence from 13 trials showed little difference between the two groups in adverse events (14/243 versus 12/206; RR 0.97, 95% CI 0.50 to 1.89), most of which were minor and short-lasting. The only major adverse event in the injection therapy group was an Achilles tendon rupture, which happened in a trial testing corticosteroid injections. There was very low quality evidence in favour of the injection therapy group in short-term (under three months) pain (219 participants, seven trials) and in the return to sports (335 participants, seven trials). There was very low quality evidence indicating little difference between groups in patient satisfaction with treatment (152 participants, four trials). There was insufficient evidence to conclude on subgroup differences based on mode of action given that only two trials tested injury-causing agents and the clear heterogeneity of the other 13 trials, which tested seven different therapies that act directly on the repair pathway. Authors' conclusions: There is insufficient evidence from randomised controlled trials to draw conclusions on the use, or to support the routine use, of injection therapies for treating Achilles tendinopathy. This review has highlighted a need for definitive research in the area of injection therapies for Achilles tendinopathy, including in older non-athletic populations. This review has shown that there is a consensus in the literature that placebo-controlled trials are considered the most appropriate trial design

Achilles tendon rupture rehabilitation : a mixed methods investigation of current practice among orthopaedic surgeons in the United Kingdom

Abstract OBJECTIVES: The evidence base to inform the management of Achilles tendon rupture is sparse. The objectives of this research were to establish what current practice is in the United Kingdom and explore clinicians' views on proposed further research in this area. This study was registered with the ISRCTN (ISRCTN68273773) as part of a larger programme of research. METHODS: We report an online survey of current practice in the United Kingdom, approved by the British Orthopaedic Foot and Ankle Society and completed by 181 of its members. A total of ten of these respondents were invited for a subsequent one-to-one interview to explore clinician views on proposed further research in this area. RESULTS: The survey showed wide variations in practice, with patients being managed in plaster cast alone (13%), plaster cast followed by orthoses management (68%), and orthoses alone (19%). Within these categories, further variation existed regarding the individual rehabilitation facets, such as the length of time worn, the foot position within them and weight-bearing status. The subsequent interviews reflected this clinical uncertainty and the pressing need for definitive research. CONCLUSIONS: The gap in evidence in this area has resulted in practice in the United Kingdom becoming varied and based on individual opinion. Future high-quality randomised trials on this subject are supported by the clinical community. Cite this article: Bone Joint Res 2015;4:65-9. ©2015 The British Editorial Society of Bone & Joint Surgery. KEYWORDS: Achilles tendon; Orthotics; Plaster Cast; Rehabilitation; Ruptur

Protocol for a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus single-agent femoral nerve blockade as analgesia for total knee arthroplasty: Perioperative Analgesia for Knee Arthroplasty (PAKA)

Introduction: Total knee arthroplasty (TKA) surgery causes postoperative pain. The use of perioperative injections around the knee containing local anaesthetic, opiates and non-steroidal anti-inflammatory drugs has increased in popularity to manage pain. Theoretical advantages include reduced requirements for analgesia and earlier mobilisation. We propose a single-centre randomised controlled trial of multimodal periarticular anaesthetic infiltration versus femoral nerve anaesthetic blockade as analgesia for TKA. The aim is to determine, in patients undergoing TKA, if there is a difference in patient-reported pain scores on the visual analogue scale (VAS) prior to physiotherapy on day 1 postoperatively between treatment groups. Methods and analysis: Patients undergoing a primary unilateral TKA at University Hospitals Coventry and Warwickshire Hospitals will be assessed for eligibility. A total of 264 patients will provide 90% power to detect a difference of 12 mm on the VAS on day 1 postoperatively at the 5% level. The trial will use 1:1 randomisation, stratified by mode of anaesthetic. Primary outcome measure will be the VAS for pain prior to physiotherapy on day 1. Secondary outcome measures include VAS on day 2, total use of opiate analgesia up to 48 h, ordinal pain scores up to 40 min after surgery, independent functional knee physiotherapist assessment on days 1 and 2. Oxford knee Scores (OKS), EuroQol (EQ-5D) and Douleur Neuropathic Pain Scores (DN2) will be recorded at baseline, 6 weeks and 12 months. Adverse events will be recorded up to 12 months. Analysis will investigate differences in VAS on day 1 between the two treatment groups on an intention-to-treat basis. Tests will be two-sided and considered to provide evidence for a significant difference if p values are less than 0.05. Ethics and dissemination: NRES Committee West Midlands, 23 September 2013 (ref: 13/WM/0316). The results will be disseminated via peer-reviewed publications and conference presentations. Trial registration numbers: ISRCTN 60611146 and EUDRACT Number 2013-002439-10 (protocol code number PAKA-33601-AS117013); Pre-results

A pragmatic randomised controlled trial comparing the efficacy of a femoral nerve block and periarticular infiltration for early pain relief following total knee arthroplasty

Aims The aim of this study was to compare the effectiveness of a femoral nerve block and a periarticular infiltration in the management of early post-operative pain after total knee arthroplasty (TKA). Patents and methods A pragmatic, single centre, two arm parallel group, patient blinded, randomised controlled trial was undertaken. All patients due for TKA were eligible. Exclusion criteria included contraindications to the medications involved in the study and patients with a neurological abnormality of the lower limb. Patients received either a femoral nerve block with 75 mg of 0.25% levobupivacaine hydrochloride around the nerve, or periarticular infiltration with 150 mg of 0.25% levobupivacaine hydrochloride, 10 mg morphine sulphate, 30 mg ketorolac trometamol and 0.25 mg of adrenaline all diluted with 0.9% saline to make a volume of 150 ml. Results A total of 264 patients were recruited and data from 230 (88%) were available for the primary analysis. Intention-to-treat analysis of the primary outcome measure of a visual analogue score for pain on the first post-operative day, prior to physiotherapy, was similar in both groups. The mean difference was -0.7 (95% confidence interval (CI) -5.9 to 4.5; p = 0.834). The periarticular group used less morphine in the first post-operative day compared with the femoral nerve block group (74%, 95% CI 55 to 99). The femoral nerve block group reported 39 adverse events, of which 27 were serious, in 31 patients and the periarticular group reported 51 adverse events, of which 38 were serious, in 42 patients up to six weeks post-operatively. None of the adverse events were directly attributed to either of the interventions under investigation. Conclusion Periarticular infiltration is a viable and safe alternative to femoral nerve block for the early post-operative relief of pain following TKA. Cite this article: Bone Joint J 2017;99-B:904-11

A protocol for a feasibility randomised controlled trial to assess the difference between functional bracing and plaster cast for the treatment of ankle fractures

Background: UK Hospital Episode Statistics 2013–2014 recorded 57,286 fractures of the lower limb including the ankle. This figure is expected to continue to increase due to a greater population of older adults. Following an ankle fracture, patients usually have their ankle immobilised with a plaster cast. This provides maximum support for the healing ankle but is associated with stiffness and muscle wasting. A Cochrane Review has concluded that functional bracing may reduce muscle wasting and speed recovery of ankle movement. The aim of this study is to determine the feasibility of conducting a full randomised controlled trial in adults with an ankle fracture followed by functional bracing and exercises versus standard plaster cast care. Methods: This is a single-centre feasibility randomised controlled trial. All patients with a fractured ankle are potentially eligible. The trial will employ 1:1 random allocation, stratified by age and non-operative/operative management. Baseline demographic and pre-injury functional data, the Manchester-Oxford Foot and Ankle Questionnaire (MOXFQ) and Olerud and Molander Ankle Score (OMAS) will be collected alongside the EuroQol EQ-5D-5 L health-related quality of life questionnaire. A research associate will perform a clinical assessment and obtain X-rays in 6 weeks and 6 months post randomisation to record complications. Functional outcome and health-related quality of life will be collected in 6 weeks, 3 and 6 months post randomisation. Discussion: This feasibility trial will provide authoritative high-quality evidence to inform the design of a definitive trial in this important area

The comprehensive cohort model in a pilot trial in orthopaedic trauma

Background: The primary aim of this study was to provide an estimate of effect size for the functional outcome of operative versus non-operative treatment for patients with an acute rupture of the Achilles tendon using accelerated rehabilitation for both groups of patients. The secondary aim was to assess the use of a comprehensive cohort research design (i.e. a parallel patient-preference group alongside a randomised group) in improving the accuracy of this estimate within an orthopaedic trauma setting. Methods: Pragmatic randomised controlled trial and comprehensive cohort study within a level 1 trauma centre. Twenty randomised participants (10 operative and 10 non-operative) and 29 preference participants (3 operative and 26 non-operative). The ge range was 22-72 years and 37 of the 52 patients were men. All participants had an acute rupture of their Achilles tendon and no other injuries. All of the patients in the operative group had a simple end-to-end repair of the tendon with no augmentation. Both groups then followed the same eight-week immediate weight-bearing rehabilitation programme using an off-the-shelf orthotic. The disability rating index (DRI; primary outcome), EQ-5D, Achilles Total Rupture Score and complications were assessed ed at two weeks, six weeks, three months, six months and nine months after initial injury. Results: At nine months, there was no significant difference in DRI between patients randomised to operative or non-operative management. There was no difference in DRI between the randomised group and the parallel patient preference group. The use of a comprehensive cohort of patients did not provide useful additional information as to the treatment effect size because the majority of patients chose non-operative management. Conclusions: Recruitment to clinical trials that compare operative and non-operative interventions is notoriously difficult; especially within the trauma setting. Including a parallel patient preference group to create a comprehensive cohort of patients has been suggested as a way of increasing the power of such trials. In our study, the comprehensive cohort model doubled the number of patients involved in the study. However, a strong preference for non-operative treatment meant that the increased number of patients did not significantly increase the ability of the trial to detect a difference between the two interventions

Characterizing Signal Loss in the 21 cm Reionization Power Spectrum: A Revised Study of PAPER-64

The Epoch of Reionization (EoR) is an uncharted era in our Universe's history during which the birth of the first stars and galaxies led to the ionization of neutral hydrogen in the intergalactic medium. There are many experiments investigating the EoR by tracing the 21cm line of neutral hydrogen. Because this signal is very faint and difficult to isolate, it is crucial to develop analysis techniques that maximize sensitivity and suppress contaminants in data. It is also imperative to understand the trade-offs between different analysis methods and their effects on power spectrum estimates. Specifically, with a statistical power spectrum detection in HERA's foreseeable future, it has become increasingly important to understand how certain analysis choices can lead to the loss of the EoR signal. In this paper, we focus on signal loss associated with power spectrum estimation. We describe the origin of this loss using both toy models and data taken by the 64-element configuration of the Donald C. Backer Precision Array for Probing the Epoch of Reionization (PAPER). In particular, we highlight how detailed investigations of signal loss have led to a revised, higher 21cm power spectrum upper limit from PAPER-64. Additionally, we summarize errors associated with power spectrum error estimation that were previously unaccounted for. We focus on a subset of PAPER-64 data in this paper; revised power spectrum limits from the PAPER experiment are presented in a forthcoming paper by Kolopanis et al. (in prep.) and supersede results from previously published PAPER analyses.Comment: 25 pages, 18 figures, Accepted by Ap

Mitigating alemtuzumab-associated autoimmunity in MS: A whack-a-mole B-cell depletion strategy

Objective: To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity. Methods: In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m2), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy. Results: Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed. Conclusions: An anti-CD20 whack-a-mole B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation. Classification of evidence: This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases

What Next-Generation 21 cm Power Spectrum Measurements Can Teach Us About the Epoch of Reionization

A number of experiments are currently working towards a measurement of the 21 cm signal from the Epoch of Reionization. Whether or not these experiments deliver a detection of cosmological emission, their limited sensitivity will prevent them from providing detailed information about the astrophysics of reionization. In this work, we consider what types of measurements will be enabled by a next-generation of larger 21 cm EoR telescopes. To calculate the type of constraints that will be possible with such arrays, we use simple models for the instrument, foreground emission, and the reionization history. We focus primarily on an instrument modeled after the $\sim 0.1~\rm{km}^2$ collecting area Hydrogen Epoch of Reionization Array (HERA) concept design, and parameterize the uncertainties with regard to foreground emission by considering different limits to the recently described "wedge" footprint in k-space. Uncertainties in the reionization history are accounted for using a series of simulations which vary the ionizing efficiency and minimum virial temperature of the galaxies responsible for reionization, as well as the mean free path of ionizing photons through the IGM. Given various combinations of models, we consider the significance of the possible power spectrum detections, the ability to trace the power spectrum evolution versus redshift, the detectability of salient power spectrum features, and the achievable level of quantitative constraints on astrophysical parameters. Ultimately, we find that $0.1~\rm{km}^2$ of collecting area is enough to ensure a very high significance ($\gtrsim30\sigma$) detection of the reionization power spectrum in even the most pessimistic scenarios. This sensitivity should allow for meaningful constraints on the reionization history and astrophysical parameters, especially if foreground subtraction techniques can be improved and successfully implemented.Comment: 27 pages, 18 figures, updated SKA numbers in appendi