Publications by authors named "Ruth Knight"

19 Publications

  • Page 1 of 1

Outpatient physiotherapy versus home-based rehabilitation for patients at risk of poor outcomes after knee arthroplasty: CORKA RCT.

Health Technol Assess 2020 11;24(65):1-116

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: Over 100,000 primary knee arthroplasty operations are undertaken annually in the UK. Around 15-30% of patients do not report a good outcome. Better rehabilitation strategies may improve patient-reported outcomes.

Objectives: To compare the outcomes from a traditional outpatient physiotherapy model with those from a home-based rehabilitation programme for people assessed as being at risk of a poor outcome after knee arthroplasty.

Design: An individually randomised, two-arm controlled trial with a blinded outcome assessment, a parallel health economic evaluation and a nested qualitative study.

Setting: The trial took place in 14 NHS physiotherapy departments.

Participants: People identified as being at high risk of a poor outcome after knee arthroplasty.

Interventions: A multicomponent home-based rehabilitation package delivered by rehabilitation assistants with supervision from qualified therapists compared with usual-care outpatient physiotherapy.

Main Outcome Measures: The primary outcome was the Late Life Function and Disability Instrument at 12 months. Secondary outcomes were the Oxford Knee Score (a disease-specific measure of function); Knee injury and Osteoarthritis Outcome Score; Quality of Life subscale; Physical Activity Scale for the Elderly; EuroQol-5 Dimensions, five-level version; and physical function assessed using the Figure-of-8 Walk Test, 30-Second Chair Stand Test and Single Leg Stance. Data on the use of health-care services, time off work and informal care were collected using participant diaries.

Results: In total, 621 participants were randomised. A total of 309 participants were assigned to the COmmunity based Rehabilitation after Knee Arthroplasty (CORKA) home-based rehabilitation programme, receiving a median of five treatment sessions (interquartile range 4-7 sessions). A total of 312 participants were assigned to usual care, receiving a median of four sessions (interquartile range 2-6 sessions). The primary outcome, Late Life Function and Disability Instrument function total score at 12 months, was collected for 279 participants (89%) in the home-based CORKA group and 287 participants (92%) in the usual-care group. No clinically or statistically significant difference was found between the groups (intention-to-treat adjusted difference 0.49 points, 95% confidence interval -0.89 to 1.88 points;  = 0.48). There were no statistically significant differences between the groups in any of the patient-reported or physical secondary outcome measures at 6 or 12 months post randomisation. The health economic analysis found that the CORKA intervention was cheaper to provide than usual care (£66 less per participant). Total societal costs (combining health-care costs and other costs) were lower for the CORKA intervention than usual care (£316 less per participant). Adopting a societal perspective, CORKA had a 75% probability of being cost-effective at a threshold of £30,000 per quality-adjusted life-year. Adopting the narrower health and social care perspective, CORKA had a 43% probability of being cost-effective at the same threshold.

Limitations: The interventions were of short duration and were set within current commissioning guidance for UK physiotherapy. Participants and treating therapists could not be blinded.

Conclusions: This randomised controlled trial found no important differences in outcomes when post-arthroplasty rehabilitation was delivered using a home-based, rehabilitation assistant-delivered rehabilitation package or a traditional outpatient model. However, the health economic evaluation found that when adopting a societal perspective, the CORKA home-based intervention was cost-saving and more effective than, and thus dominant over, usual care, owing to reduced time away from paid employment for this group. Further research could look at identifying the risk of poor outcome and further evaluation of a cost-effective treatment, including the workforce model to deliver it.

Trial Registration: Current Controlled Trials ISRCTN13517704.

Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 65. See the NIHR Journals Library website for further project information.
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http://dx.doi.org/10.3310/hta24650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750865PMC
November 2020

A multicentre prospective randomized equivalence trial of a soft bandage and immediate discharge versus current treatment with rigid immobilization for torus fractures of the distal radius in children: protocol for the Forearm Fracture Recovery in Children Evaluation (FORCE) trial.

Bone Jt Open 2020 Jun 8;1(6):214-221. Epub 2020 Jun 8.

Oxford Trauma, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Aims: Torus fractures are the most common childhood fracture, accounting for 500,000 UK emergency attendances per year. UK treatment varies widely due to lack of scientific evidence. This is the protocol for a randomized controlled equivalence trial of 'the offer of a soft bandage and immediate discharge' versus 'rigid immobilization and follow-up as per the protocol of the treating centre' in the treatment of torus fractures .

Methods: Children aged four to 15-years-old inclusive who have sustained a torus/buckle fracture of the distal radius with/without an injury to the ulna are eligible to take part. Baseline pain as measured by the Wong Baker FACES pain scale, function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb, and quality of life (QoL) assessed with the EuroQol EQ-5D-Y will be collected. Each patient will be randomly allocated (1:1, stratified by centre and age group (four to seven years and ≥ eight years) to either a regimen of the offer of a soft bandage and immediate discharge or rigid immobilization and follow-up as per the protocol of the treating centre.

Results: At day one, three, and seven, data on pain, function, QoL, immobilization, and analgesia will be collected. Three and six weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the Wong-Baker FACES pain scale at three days post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardian.Cite this article: 2020;1-6:214-221.
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http://dx.doi.org/10.1302/2633-1462.16.BJO-2020-0014.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677722PMC
June 2020

The Forearm Fracture Recovery in Children Evaluation (FORCE) trial: statistical and health economic analysis plan for an equivalence randomized controlled trial of treatment for torus fractures of the distal radius in children.

Bone Jt Open 2020 Jun 9;1(6):205-213. Epub 2020 Jun 9.

Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Oxford, UK.

Aims: Torus fractures of the distal radius are the most common fractures in children. The NICE non-complex fracture guidelines recently concluded that bandaging was probably the optimal treatment for these injuries. However, across the UK current treatment varies widely due to a lack of evidence underpinning the guidelines. The Forearm Fracture Recovery in Children Evaluation (FORCE) trial evaluates the effect of a soft bandage and immediate discharge compared with rigid immobilization.

Methods: FORCE is a multicentre, parallel group randomized controlled equivalence trial. The primary outcome is the Wong-Baker FACES pain score at three days after randomization and the primary analysis of this outcome will use a multivariate linear regression model to compare the two groups. Secondary outcomes are measured at one and seven days, and three and six-weeks post-randomization and include the Patient Reported Outcome Measurement Information System (PROMIS) upper extremity limb score, EuroQoL EQ-5D-Y, analgesia use, school absence, complications, and healthcare resource use. The planned statistical and health economic analyses for this trial are described here. The FORCE trial protocol has been published separately.

Conclusion: This paper provides details of the planned analyses for this trial, and will reduce the risks of outcome reporting bias and data driven results.Cite this article: 2020;1-6:205-213.
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http://dx.doi.org/10.1302/2633-1462.16.BJO-2020-0015.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677725PMC
June 2020

The Orthopaedic Trauma Society classification of open fractures.

Bone Joint J 2020 Nov;102-B(11):1469-1474

Oxford Trauma and Emergency Care, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Aims: To describe a new objective classification for open fractures of the lower limb and to correlate the classification with patient-centred outcomes.

Methods: The proposed classification was investigated within a cohort of adults with open fractures of the lower limb who were recruited as part of two large clinical trials within the UK Major Trauma Network. The classification was correlated with patient-reported Disability Rating Index (DRI) and EuroQol five-dimension questionnaire (EQ-5D) health-related quality of life in the year after injury, and with deep infection at 30 days, according to the Centers for Disease Control and Prevention definition of a deep surgical site infection.

Results: A total of 748 participants were included in the analysis. Of these, 288 (38.5%) had a simple open fracture and 460 (61.5%) had a complex fracture as defined by the new classification system. At 12 months, the mean DRI in the simple fracture group was 32.5 (SD 26.8) versus 43.9 (SD 26.1) in the complex fracture group (odds ratio (OR) 8.19; 95% confidence interval (CI) 3.69 to 12.69). At 12 months the mean health-related quality of life (EQ-5D utility) in the simple fracture group was 0.59 (SD 0.29) versus 0.56 (SD 0.32) in the complex fracture group (OR -0.03; 95% CI -0.09 to 0.02). The differences in the rate of deep infection at 30 days was not statistically significant.

Conclusion: The Orthopaedic Trauma Society open fracture classification is based upon objective descriptors of the injury and correlates with patient-centred outcomes in a large cohort of open fractures of the lower limb. Cite this article: 2020;102-B(11):1469-1474.
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http://dx.doi.org/10.1302/0301-620X.102B11.BJJ-2020-0825.R1DOI Listing
November 2020

Infographic: The Orthopaedic Trauma Society classification of open fractures.

Bone Joint J 2020 Nov;102-B(11):1467-1468

Oxford Trauma and Emergency Care, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, United Kingdom.

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http://dx.doi.org/10.1302/0301-620X.102B11.BJJ-2020-1998DOI Listing
November 2020

Negative-pressure wound therapy compared with standard dressings following surgical treatment of major trauma to the lower limb: the WHiST RCT.

Health Technol Assess 2020 08;24(38):1-86

Oxford Trauma, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.

Background: Major trauma is the leading cause of death in people aged < 45 years. Patients with major trauma usually have lower-limb fractures. Surgery to fix the fractures is complicated and the risk of infection may be as high as 27%. The type of dressing applied after surgery could potentially reduce the risk of infection.

Objectives: To assess the deep surgical site infection rate, disability, quality of life, patient assessment of the surgical scar and resource use in patients with surgical incisions associated with fractures following major trauma to the lower limbs treated with incisional negative-pressure wound therapy versus standard dressings.

Design: A pragmatic, multicentre, randomised controlled trial.

Setting: Twenty-four specialist trauma hospitals representing the UK Major Trauma Network.

Participants: A total of 1548 adult patients were randomised from September 2016 to April 2018. Exclusion criteria included presentation > 72 hours after injury and inability to complete questionnaires.

Interventions: Incisional negative-pressure wound therapy ( = 785), in which a non-adherent absorbent dressing covered with a semipermeable membrane is connected to a pump to create a partial vacuum over the wound, versus standard dressings not involving negative pressure ( = 763). Trial participants and the treating surgeon could not be blinded to treatment allocation.

Main Outcome Measures: Deep surgical site infection at 30 days was the primary outcome measure. Secondary outcomes were deep infection at 90 days, the results of the Disability Rating Index, health-related quality of life, the results of the Patient and Observer Scar Assessment Scale and resource use collected at 3 and 6 months post surgery.

Results: A total of 98% of participants provided primary outcome data. There was no evidence of a difference in the rate of deep surgical site infection at 30 days. The infection rate was 6.7% (50/749) in the standard dressing group and 5.8% (45/770) in the incisional negative-pressure wound therapy group (intention-to-treat odds ratio 0.87; 95% confidence interval 0.57 to 1.33;  = 0.52). There was no difference in the deep surgical site infection rate at 90 days: 13.2% in the standard dressing group and 11.4% in the incisional negative-pressure wound therapy group (odds ratio 0.84, 95% confidence interval 0.59 to 1.19;  = 0.32). There was no difference between the two groups in disability, quality of life or scar appearance at 3 or 6 months. Incisional negative-pressure wound therapy did not reduce the cost of treatment and was associated with a low probability of cost-effectiveness.

Limitations: Owing to the emergency nature of the surgery, we anticipated that some patients who were randomised would subsequently be unable or unwilling to participate. However, the majority of the patients (85%) agreed to participate. Therefore, participants were representative of the population with lower-limb fractures associated with major trauma.

Conclusions: The findings of this study do not support the use of negative-pressure wound therapy in patients having surgery for major trauma to the lower limbs.

Future Work: Our work suggests that the use of incisional negative-pressure wound therapy dressings in other at-risk surgical wounds requires further investigation. Future research may also investigate different approaches to reduce postoperative infections, for example the use of topical antibiotic preparations in surgical wounds and the role of orthopaedic implants with antimicrobial coatings when fixing the associated fracture.

Trial Registration: Current Controlled Trials ISRCTN12702354 and UK Clinical Research Network Portfolio ID20416.

Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in ; Vol. 24, No. 38. See the NIHR Journals Library for further project information.
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http://dx.doi.org/10.3310/hta24380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457061PMC
August 2020

Current practice in analysing and reporting binary outcome data-a review of randomised controlled trial reports.

BMC Med 2020 06 8;18(1):147. Epub 2020 Jun 8.

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.

Background: Randomised controlled trials (RCTs) need to be reported so that their results can be unambiguously and robustly interpreted. Binary outcomes yield unique challenges, as different analytical approaches may produce relative, absolute, or no treatment effects, and results may be particularly sensitive to the assumptions made about missing data. This review of recently published RCTs aimed to identify the methods used to analyse binary primary outcomes, how missing data were handled, and how the results were reported.

Methods: Systematic review of reports of RCTs published in January 2019 that included a binary primary outcome measure. We identified potentially eligible English language papers on PubMed, without restricting by journal or medical research area. Papers reporting the results from individually randomised, parallel-group RCTs were included.

Results: Two hundred reports of RCTs were included in this review. We found that 64% of the 200 reports used a chi-squared-style test as their primary analytical method. Fifty-five per cent (95% confidence interval 48% to 62%) reported at least one treatment effect measure, and 38% presented only a p value without any treatment effect measure. Missing data were not always adequately described and were most commonly handled using available case analysis (69%) in the 140 studies that reported missing data. Imputation and best/worst-case scenarios were used in 21% of studies. Twelve per cent of articles reported an appropriate sensitivity analysis for missing data.

Conclusions: The statistical analysis and reporting of treatment effects in reports of randomised trials with a binary primary endpoint requires substantial improvement. Only around half of the studied reports presented a treatment effect measure, hindering the understanding and dissemination of the findings. We also found that published trials often did not clearly describe missing data or sensitivity analyses for these missing data. Practice for secondary endpoints or observational studies may differ.
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http://dx.doi.org/10.1186/s12916-020-01598-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278160PMC
June 2020

Effect of Incisional Negative Pressure Wound Therapy vs Standard Wound Dressing on Deep Surgical Site Infection After Surgery for Lower Limb Fractures Associated With Major Trauma: The WHIST Randomized Clinical Trial.

JAMA 2020 02;323(6):519-526

Oxford Trauma, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, England.

Importance: Following surgery to treat major trauma-related fractures, deep wound infection rates are high. It is not known if negative pressure wound therapy can reduce infection rates in this setting.

Objective: To assess outcomes in patients who have incisions resulting from surgery for lower limb fractures related to major trauma and were treated with either incisional negative pressure wound therapy or standard wound dressing.

Design, Setting, And Participants: A randomized clinical trial conducted at 24 trauma hospitals representing the UK Major Trauma Network that included 1548 patients aged 16 years or older who underwent surgery for a lower limb fracture caused by major trauma from July 7, 2016, through April 17, 2018, with follow-up to December 11, 2018.

Interventions: Incisional negative pressure wound therapy (n = 785), which involved a specialized dressing used to create negative pressure over the wound, vs standard wound dressing not involving negative pressure (n = 763).

Main Outcomes And Measures: The primary outcome measure was deep surgical site infection at 30 days diagnosed according to the criteria from the US Centers for Disease Control and Prevention. A preplanned secondary analysis of the primary outcome was performed at 90 days. The secondary outcomes were patient-reported disability (Disability Rating Index), health-related quality of life (EuroQol 5-level EQ-5D), surgical scar assessment (Patient and Observer Scar Assessment Scale), and chronic pain (Douleur Neuropathique Questionnaire) at 3 and 6 months, as well as other local wound healing complications at 30 days.

Results: Among 1548 participants who were randomized (mean [SD] age, 49.8 [20.3] years; 561 [36%] were aged ≤40 years; 583 [38%] women; and 881 [57%] had multiple injuries), 1519 (98%) had data available for the primary outcome. At 30 days, deep surgical site infection occurred in 5.84% (45 of 770 patients) of the incisional negative pressure wound therapy group and in 6.68% (50 of 749 patients) of the standard wound dressing group (odds ratio, 0.87 [95% CI, 0.57 to 1.33]; absolute risk difference, -0.77% [95% CI, -3.19% to 1.66%]; P = .52). There was no significant difference in the deep surgical site infection rate at 90 days (11.4% [72 of 629 patients] in the incisional negative pressure wound therapy group vs 13.2% [78 of 590 patients] in the standard wound dressing group; odds ratio, 0.84 [95% CI, 0.59 to 1.19]; absolute risk difference, -1.76% [95% CI, -5.41% to 1.90%]; P = .32). For the 5 prespecified secondary outcomes reported, there were no significant differences at any time point.

Conclusions And Relevance: Among patients who underwent surgery for major trauma-related lower limb fractures, use of incisional negative pressure wound therapy, compared with standard wound dressing, resulted in no significant difference in the rate of deep surgical site infection. The findings do not support the use of incisional negative pressure wound therapy in this setting, although the event rate at 30 days was lower than expected.

Trial Registration: isrctn.org Identifier: ISRCTN12702354.
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http://dx.doi.org/10.1001/jama.2020.0059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042841PMC
February 2020

Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK): study protocol for a patient-blinded, randomised controlled superiority trial of liposomal bupivacaine.

Trials 2019 Dec 16;20(1):732. Epub 2019 Dec 16.

Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.

Background: Optimising the management of peri-operative pain and recovery following knee replacement has been identified as a patient priority. Current pain relief strategies use opiate-based analgesia; however, up to 50% of patients experience significant side effects. Local anaesthetic incisional infiltration is one alternative. The length of the duration of action is a major limiting factor of current local anaesthetic techniques. Liposomal bupivacaine has been reported to be effective for up to 72 h. This randomised controlled trial will evaluate the clinical and cost effectiveness of liposomal bupivacaine.

Methods: SPAARK is a patient-blinded, multi-centre, active comparator, superiority, two-arm, parallel-group randomised controlled trial. Five hundred patients undergoing knee replacement will be recruited and randomised to liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The co-primary outcomes are the Quality of Recovery 40 measured at 72 h post-surgery and also cumulative pain measured daily using a 0-10 visual analogue scale for the first 3 days following surgery. Secondary outcomes include cumulative opioid consumption, fitness for discharge, functional outcomes assessed using the Oxford Knee Score and American Knee Society Score, the EuroQol five dimensions instrument and complications. A cost utility analysis is also planned.

Discussion: The clinical effectiveness and cost effectiveness of liposomal bupivacaine have yet to be evaluated in the National Health Service, making this trial appropriate and timely.

Trial Registration: ISRCTN registry, ISRCTN54191675. Registered on 14 November 2017.
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http://dx.doi.org/10.1186/s13063-019-3826-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915937PMC
December 2019

Distinct neural response to visual perspective and body size in the extrastriate body area.

Behav Brain Res 2019 10 27;372:112063. Epub 2019 Jun 27.

Department of Psychology, University of York, York, United Kingdom.

Neuroimaging research has independently implicated the extrastriate body area (EBA) in distinguishing between different visual perspectives and morphologies of bodies within visual processing. However, the combined processing of these physical attributes towards neural EBA response remains unclear, and may be crucial in influencing higher-order, aesthetic evaluation of bodies. Indeed, EBA alterations amongst eating disorder patients have been associated with disturbances in body image, and disruption to EBA activity amongst healthy individuals has been shown to influence aesthetic evaluations made towards bodies. Therefore, the present study used images of slim and large female bodies viewed from egocentric and allocentric perspectives, to investigate neural EBA response amongst healthy females (N = 30). In addition, participants provided behavioural aesthetic and weight evaluations of all model stimuli. Results revealed an interaction, bilaterally, between visual perspective and body size towards EBA activity, with multi-voxel pattern analysis revealing distinct neural patterns between the four conditions. However, EBA activity did not relate to non-clinical eating disorder psychopathology. No direct relationship was found between EBA activity and behavioural evaluations of model stimuli; however, a whole brain analysis revealed that higher-order, prefrontal regions were associated with cognitive evaluations of large bodies. Taken together, our results suggest that the EBA is an integral core region in discriminating between multiple physical attributes of the body, which is likely to provide important information to higher-order brain regions which make aesthetic evaluations towards bodies.
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http://dx.doi.org/10.1016/j.bbr.2019.112063DOI Listing
October 2019

Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships.

J Med Chem 2019 06 23;62(12):5863-5884. Epub 2019 May 23.

Cancer Research UK Centre for Cancer Therapeutics , The Institute of Cancer Research , 15 Cotswold Road , London SM2 5NG , United Kingdom.

Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing an aminomethylenethiophene (AMT) scaffold. High-throughput screening provided the initial hits. Structure-activity relationship (SAR) studies led to the discovery of AMT inhibitors with sub-micromolar half-maximal inhibitory concentrations (IC) in a LOX enzyme activity assay. Further SAR optimization yielded the orally bioavailable LOX inhibitor CCT365623 with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.
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http://dx.doi.org/10.1021/acs.jmedchem.9b00335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937593PMC
June 2019

Wound Healing In Surgery for Trauma (WHIST): statistical analysis plan for a randomised controlled trial comparing standard wound management with negative pressure wound therapy.

Trials 2019 Mar 28;20(1):186. Epub 2019 Mar 28.

Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Windmill Road, Oxford, OX3 7LD, UK.

Background: In the context of major trauma, the rate of wound infection in surgical incisions created during fracture fixation amongst patients with closed high-energy injuries is high. One of the factors which may reduce the risk of surgical site infection is the type of dressing applied over the closed incision. The WHIST trial evaluates the effects of negative-pressure wound therapy (NPWT) compared with standard dressings.

Methods/design: The WHIST trial is a multicentre, parallel group, randomised controlled trial. The primary outcome is the rate of deep surgical site infection at 30 days after major trauma. Secondary outcomes are measured at 3 and 6 months post-randomisation and include the Disability Rating Index, the EuroQoL EQ-5D-5 L, the Doleur Neuropathique Questionnaire, a patient-reported scar assessment, and record of complications. The analysis approaches for the primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. The full WHIST protocol has already been published.

Discussion: This paper provides details of the planned statistical analyses for this trial and will reduce the risks of outcome reporting bias and data driven results.

Trial Registration: International Standard Randomised Controlled Trials database, ISRCTN12702354 . Registered on 9 December 2015.
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http://dx.doi.org/10.1186/s13063-019-3282-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438006PMC
March 2019

Eating Disorder Examination Questionnaire (EDE-Q): Norms and psychometric properties in U.K. females and males.

Psychol Assess 2019 Jul 25;31(7):839-850. Epub 2019 Feb 25.

Department of Psychology, University of York.

The Eating Disorder Examination Questionnaire (EDE-Q) is a widely used assessment of eating disorder psychopathology; however, EDE-Q norms are yet to be provided within a nonclinical U.K. adult sample. Second, there is considerable disagreement regarding the psychometric properties of this measure. Several alternative factor structures have been previously proposed, but very few have subsequently validated their new structure in independent samples and many are often confined to specific subpopulations. Therefore, in the current study, we provide norms of the original four-factor EDE-Q structure, and subsequently assess the psychometric properties of the EDE-Q in females and males using a large nonclinical U.K. sample (total N = 2459). EDE-Q norms were consistently higher in females compared with males across all samples. Initial confirmatory factor analyses (CFA) did not support the original 4-factor structure for females or males (Phase 1). However, subsequent exploratory factor analyses (EFA) revealed a 3-factor structure as being the optimal fit for both females and males, using an 18-item and 16-item model, respectively (Phase 2). For females, the newly proposed 18-item structure was validated within an independent student sample and further validated in an additional nonstudent sample. The 16-item 3-factor male structure was also validated within an independent nonstudent sample, but was marginally below accepted fit indices within an independent student sample (Phase 3). Taken together, the above findings suggest that the EDE-Q factor structure may require further reassessment, with greater focus on the qualitative differences in interpretation of EDE-Q items between females and males. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/pas0000703DOI Listing
July 2019

A scoping review of the problems and solutions associated with contamination in trials of complex interventions in mental health.

BMC Med Res Methodol 2019 01 7;19(1). Epub 2019 Jan 7.

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, 16 De Crespigny Park, London, SE5 8AF, United Kingdom.

Background: In a randomised controlled trial, contamination is defined as the receipt of active intervention amongst participants in the control arm. This review assessed the processes leading to contamination, its typical quantity, methods used to mitigate it, and impact of use of cluster randomisation to prevent it on study findings in trials of complex interventions in mental health.

Methods: This is a scoping review of trial design approaches and methods of study conduct to address contamination. Studies included were randomised controlled trials of complex interventions in mental health that described the process leading to, amount of, or solution used to counter contamination. The Medline, Embase, and PsycInfo databases were searched for trials published between 2000 and 2015. Risk of bias was assessed using the Jadad score and domains recommended by Cochrane plus some relevant to cluster randomised trials.

Results: Two hundred and thirty-four articles were included in the review. The main processes that led to contamination were health professionals delivering both active and comparator treatments and communication among clinicians and participants from the different trial arms. Twenty-three trials (10%) measured binary treatment receipt in the control arm with median 13% of participants found to be contaminated (IQR 5-33%). The most common design approach for dealing with contamination was the use of cluster randomisation (n = 93). In addition, many researchers used simple trial conduct methods to minimise contamination due to suspected contamination processes, such as organising for each clinician to provide only one treatment and separating trial arms spatially or temporally. There was little evidence for a relationship between cluster randomisation to avoid contamination and size of treatment effect estimate.

Conclusion: There was some evidence of modest levels of treatment contamination with a large range, although a minority of studies reported the amount of contamination. A limitation was that many trials described the problem in little detail. Overall there is a need for greater measurement and reporting of treatment receipt in the control arm of trials. Researchers should be aware of trial conduct methods that can be used to minimise contamination without resorting to cluster randomisation.
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http://dx.doi.org/10.1186/s12874-018-0646-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323722PMC
January 2019

COmmunity-based Rehabilitation after Knee Arthroplasty (CORKA): statistical analysis plan for a randomised controlled trial.

Trials 2018 Nov 19;19(1):638. Epub 2018 Nov 19.

Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, OX3 7LD, UK.

Background: About 15% of patients fail to achieve a satisfactory clinical outcome following knee replacement, which may indicate the existing model of rehabilitation after surgery is possibly not the most efficacious. The COmmunity-based Rehabilitation after Knee Arthroplasty (CORKA) trial evaluates the effects of a new multi-component community-based rehabilitation programme following knee replacement compared with usual care.

Methods/design: The CORKA trial is a multi-centre, single-blind, two-arm randomised controlled trial. The primary outcome is the Late Life Function and Disability Instrument (LLFDI) overall function score measured at 12 months post-randomisation which will be analysed using a linear mixed effects model. Secondary outcomes are measured at 6 and 12 months post-randomisation and include the LLFDI frequency and limitation total dimension scores, the Oxford Knee Score, the Knee injury and Osteoarthritis Outcome Score quality of life subscale, the Physical Activity Scale for the Elderly, the EuroQol EQ-5D-5L, and several measurements of physical function. Full details of the planned analysis approaches for the primary and secondary outcomes are described here, as are the descriptive statistics which will be reported. This is an update to the CORKA protocol which has already been published in this journal.

Discussion: This paper provides details of the planned statistical analyses for this trial and will reduce the risks of outcome reporting bias and data-driven results.

Trial Registration: ISRCTN registry, 13517704 . Registered on 12 February 2015.

Funding/sponsor: The trial is funded by the National Institute for Health Research Health Technology Assessment programme under its commissioned research programme (HTA 12/196/08). The trial sponsor is the University of Oxford.
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http://dx.doi.org/10.1186/s13063-018-3031-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245938PMC
November 2018

A Systematic Review and Meta-Analysis of the Effectiveness of Acetylcholinesterase Inhibitors and Memantine in Treating the Cognitive Symptoms of Dementia.

Dement Geriatr Cogn Disord 2018 7;45(3-4):131-151. Epub 2018 May 7.

Department of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Background: Acetylcholinesterase inhibitors (AChEIs) and memantine are commonly used in the management of dementia. In routine clinical practice, dementia is often monitored via the Mini-Mental State Examination (MMSE). We conducted a systematic review and meta-analysis of the effects of these drugs on MMSE scores.

Summary: Eighty trials were identified. Pooled effect estimates were in favour of both AChEIs and memantine at 6 months. Meta-regression indicated that dementia subtype was a moderator of AChEI treatment effect, with the effect of treatment versus control twice as high for patients with Parkinson disease dementia/ dementia with Lewy bodies (2.11 MMSE points at 6 months) as for patients with Alzheimer disease/vascular dementia (0.91 MMSE points at 6 months). Key Messages: AChEIs demonstrate a modest effect versus control on MMSE scores which is moderated by dementia subtype. For memantine the effect is smaller.
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http://dx.doi.org/10.1159/000486546DOI Listing
November 2018

A social media intervention to improve hypoglycemia management at a multicenter hospital: a quality improvement pilot for clinical nurses.

Contemp Nurse 2018 Feb 5;54(1):44-51. Epub 2018 Mar 5.

a 1967 Riverside Drive, Box 215 , Ottawa , Ontario K1H 7W9 , Canada.

Background: Hypoglycemia poses significant risk to inpatients. Nursing management of hypoglycemia is a challenge, despite established best practice guidelines. Social media is an effective tool for sharing information and could overcome barriers to clinical education at a multicenter hospital.

Aims: The purpose of this quality improvement intervention was to create and disseminate social media posts about best practices in hypoglycemia management.

Design: An unmatched pre-and post-survey assessed nursing knowledge of hypoglycemia management.

Methods: Social media posts were created to visually outline the steps for hypoglycemia management over 2 weeks, across a nursing social media platform. We assessed the reach of the posts via Facebook and a survey.

Results: The posts reached 2962 users during the first week, and 1491 users the second week.

Conclusions: A social media intervention can have a substantial reach and distribute information across a multicenter hospital. Additional study is needed to determine what factors could support an increase in nursing knowledge through a social media campaign.
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http://dx.doi.org/10.1080/10376178.2018.1440180DOI Listing
February 2018

Membrane topology of Bves/Pop1A, a cell adhesion molecule that displays dynamic changes in cellular distribution during development.

J Biol Chem 2003 Aug 17;278(35):32872-9. Epub 2003 Jun 17.

Stahlman Cardiovascular Research Laboratories and Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-6300, USA.

We investigated the membrane topology of Bves/Pop1A as a foundation to dissect the molecular basis and function of Bves/Pop1A trafficking during development. Bves contains two asparagine-linked glycosylation sites within the amino terminus and three putative membrane domains. Therefore, glycosylation assays were performed to determine if the amino terminus of Bves is delivered into the endoplasmic reticulum lumen and glycosylated. We establish that Bves from chick heart and transfected cells is glycosylated, implying that the amino terminus of cell surface molecules is extracellular. Three biochemically distinct approaches were utilized to determine the orientation of the carboxyl terminus of Bves. First, glycosylation of Bves at exogenous sites within the carboxyl terminus was only observed in a construct that lacked the third membrane domain, which presumably reversed the orientation of the carboxyl terminus. Second, co-expression of full-length Bves with soluble, carboxyl-terminal Bves constructs that reside in different subcellular compartments revealed that Bves-Bves interactions occur in the cytoplasm. Third, the immunoreactivity of endogenous Bves at the cell surface of epicardial cells was dramatically enhanced with detergent. These results suggest that the membrane topology of cell surface Bves/Pop1A is composed of an extracellular amino terminus, three transmembrane domains, and a cytoplasmic carboxyl terminus. We therefore hypothesize that the carboxyl terminus regulates the cellular distribution of Bves/Pop1A during coronary vessel development.
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http://dx.doi.org/10.1074/jbc.M301961200DOI Listing
August 2003

Implementation of clinical guidelines for female urinary incontinence: a comparative analysis of organizational structures and service delivery.

Health Soc Care Community 1999 Jul;7(4):280-290

Nursing Research and Development Unit, Faculty of Health, Social Work and Education, University of Northumbria at Newcastle, Newcastle upon Tyne, UK.

The aim of the study was to explore and compare the development of continence services in two contrasting trusts. The first was a community trust which had initiated a top-down purchaser-led continence service. The second was a combined acute and community trust which had introduced a bottom-up, organic continence service based on staff development. The research used a qualitative, interpretative design. Evidence-based guidelines for female urinary incontinence (FUI) were analysed and key organizational features elicited. These were used to frame and analyse 20 semi-structured interviews with a range of community-based professionals who provided a service to women suffering from urinary incontinence. The interviews identified practitioner knowledge and awareness of the evidence pertaining to the management and treatment of FUI and also the features of the organizational structure of service provision in their locality which facilitated or constrained the implementation of evidence-based treatment in this area. The findings suggest that evidence-based guidelines were more closely adhered to in practice, in the trust using organic approaches to service development. Top-down, purchaser led approaches were more prescriptive and circumscribed the scope of professional practice. This adversely affected access to services for women suffering from urinary incontinence. Organic approaches to service development produce more flexible, responsive services. It is difficult, however, to integrate this approach with strategic planning as the flexibility required maybe incompatible with managerial responsibilities for defining roles and organizational functions.
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http://dx.doi.org/10.1046/j.1365-2524.1999.00186.xDOI Listing
July 1999