The Diagnostic Accuracy of Colon Capsule Endoscopy in Inflammatory Bowel Disease-A Systematic Review and Meta-Analysis.

Colon capsule endoscopy (CCE) has regained popularity for lower gastrointestinal investigations since the COVID-19 pandemic. While there have been systematic reviews and meta-analyses on colonic polyp detection using CCE, there is a lack of comprehensive evidence concerning colonic inflammation. Therefore, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of CCE for colonic inflammation, predominantly ulcerative colitis (UC) and Crohn's disease (CD). Methods: We systematically searched electronic databases (EMBASE, MEDLINE, PubMed Central, and Cochrane Library) for studies comparing the diagnostic accuracy between CCE and optical endoscopy as the standard reference. A bivariate random effect model was used for the meta-analysis. Results: From 3797 publications, 23 studies involving 1353 patients were included. Nine studies focused on UC, and ten focused on CD. For UC, CCE showed a pooled sensitivity of 92% (95% CI, 88-95%), a specificity of 71% (95% CI, 35-92%), and an AUC of 0.93 (95% CI, 0.89-0.97). For CD, the pooled sensitivity was 92% (95% CI, 89-95%), and the specificity was 88% (95% CI, 84-92%), with an AUC of 0.87 (95% CI, 0.76-0.98). Overall, for inflammatory bowel disease, the pooled sensitivity, specificity, and AUC were 90% (95% CI, 85-93%), 76% (95% CI, 56-90%), and 0.92 (95% CI, 0.94-0.97), respectively. Conclusions: Despite the challenges around standardised disease scoring and the lack of histological confirmation, CCE performs well in diagnosing inflammatory bowel disease. It demonstrates high sensitivity in both UC and Crohn's terminal ileitis and colitis and high specificity in Crohn's disease. Further studies are needed to evaluate the diagnostic accuracy of other colonic inflammatory conditions.

Rationalizing polyp matching criteria in colon capsule endoscopy: an international expert consensus through RAND (modified DELPHI) process.

Background: Colon capsule endoscopy (CCE) has gained momentum as an alternative modality for the investigation of the lower gastrointestinal tract. Of the few challenges that remain, the comparison and - eventually - matching of polyps at different timestamps leads to the potential for double reporting and can contribute to false-positive findings and inaccuracies. With the impending artificial intelligence integration, the risk of double reporting the same polyp due to the lack of information on spatial orientation underscores the necessity for establishing criteria for polyp matching. Objectives: This RAND/University of California, Los Angeles (modified Delphi) process aims to identify the key factors or components used to match polyps within a CCE video. This involves exploring the attributes of each factor to create comprehensive polyp-matching criteria based on international expert consensus. Design: A systematic qualitative study using surveys. Methods: A panel of 11 international CCE experts convened to assess a survey comprised of 60 statements. Participants anonymously rated statement appropriateness on a 1-9 scale (1-3: inappropriate, 4-6: uncertain and 7-9: appropriate). Following a virtual group discussion of the Round 1 results, a Round 2 survey was developed and completed before the final analysis. Results: The factors that were agreed to be essential for polyp matching include (1) timestamp, (2) polyp localization, (3) polyp vascular pattern, (4) polyp size, (5) time interval of the polyp appearance between the green and yellow camera, (6) surrounding tissue, (7) polyp morphology and (8) polyp surface and contour. When five or more factors are satisfied, it was agreed that the comparing polyps are likely the same polyp. Conclusion: This study has established the first complete criteria for polyp matching in CCE. While it might not provide a definitive solution for matching difficult, small and common polyps, these criteria serve as a framework to guide and facilitate the process of polyp-matching.

Creating criteria and standards for matching polyps (abnormal growth in the bowels) on colon capsule video analysis: an international expert agreement using the RAND (modified Delphi process) process Background: Doctors often use colon capsule endoscopy (CCE), a high-tech capsule with two cameras, to record and check for diseases in the small and large bowels as the capsule travels through the intestines. One of the most common conditions in the large bowel is polyps, which are abnormal growths in the lining of the bowel. Comparing and matching polyps in the same video from the capsule can be tricky as they look very similar, leading to the possibility of incorrectly reporting the same polyp twice or more. This can lead to wrong results and inaccuracies. The literature did not have any criteria or standards for matching polyps in CCE before. Aim: Using the RAND/UCLA (modified Delphi) process, this study aims to identify the key factors or components used to match polyps within a CCE video. The goal is to explore each factor and create complete criteria for polyp matching based on the agreement from international experts. Method: A group of 11 international CCE experts came together to evaluate a survey with 60 statements. They anonymously rated each statement on a scale from 1 to 9 (1-3: inappropriate, 4-6: uncertain, and 7-9: appropriate). After discussing the Round 1 results virtually, a Round 2 survey with the same but revised questions was created and completed before the final analysis of their agreement. Results: The main factors for matching polyps are 1) the timing when the polyp was seen, 2) where it is in the bowel, 3) its blood vessel pattern, 4) size, 5) the timing of its appearance between cameras, 6) surrounding tissue features, 7) its shape, and 8) surface features. If five or more of these factors match, the compared polyps are likely the same. Conclusion: This study establishes the first complete criteria for matching polyps in CCE. While it may not provide a definitive solution for matching challenging and small polyps, these criteria serve as a guide to help and make the process of polyp matching easier.

Service availability and readiness for hip fracture care in low- and middle-income countries in South and Southeast Asia.

Aims: The aim of this study was to describe the current pathways of care for patients with a fracture of the hip in five low- and middle-income countries (LMIC) in South Asia (Nepal and Sri Lanka) and Southeast Asia (Malaysia, Thailand, and the Philippines). Methods: The World Health Organization Service Availability and Readiness Assessment tool was used to collect data on the care of hip fractures in Malaysia, Thailand, the Philippines, Sri Lanka, and Nepal. Respondents were asked to provide details about the current pathway of care for patients with hip fracture, including pre-hospital transport, time to admission, time to surgery, and time to weightbearing, along with healthcare professionals involved at different stages of care, information on discharge, and patient follow-up. Results: Responses were received from 98 representative hospitals across the five countries. Most hospitals were publicly funded. There was consistency in clinical pathways of care within country, but considerable variation between countries. Patients mostly travel to hospital via ambulance (both publicly- and privately-funded) or private transport, with only half arriving at hospital within 12 hours of their injury. Access to surgery was variable and time to surgery ranged between one day and more than five days. The majority of hospitals mobilized patients on the first or second day after surgery, but there was notable variation in postoperative weightbearing protocols. Senior medical input was variable and specialist orthogeriatric expertise was unavailable in most hospitals. Conclusion: This study provides the first step in mapping care pathways for patients with hip fracture in LMIC in South Asia. The previous lack of data in these countries hampers efforts to identify quality standards (key performance indicators) that are relevant to each different healthcare system.

Study of capsule endoscopy delivery at scale through enhanced artificial intelligence-enabled analysis (the CESCAIL study).

AIM: Lower gastrointestinal (GI) diagnostics have been facing relentless capacity constraints for many years, even before the COVID-19 era. Restrictions from the COVID pandemic have resulted in a significant backlog in lower GI diagnostics. Given recent developments in deep neural networks (DNNs) and the application of artificial intelligence (AI) in endoscopy, automating capsule video analysis is now within reach. Comparable to the efficiency and accuracy of AI applications in small bowel capsule endoscopy, AI in colon capsule analysis will also improve the efficiency of video reading and address the relentless demand on lower GI services. The aim of the CESCAIL study is to determine the feasibility, accuracy and productivity of AI-enabled analysis tools (AiSPEED) for polyp detection compared with the 'gold standard': a conventional care pathway with clinician analysis. METHOD: This multi-centre, diagnostic accuracy study aims to recruit 674 participants retrospectively and prospectively from centres conducting colon capsule endoscopy (CCE) as part of their standard care pathway. After the study participants have undergone CCE, the colon capsule videos will be uploaded onto two different pathways: AI-enabled video analysis and the gold standard conventional clinician analysis pathway. The reports generated from both pathways will be compared for accuracy (sensitivity and specificity). The reading time can only be compared in the prospective cohort. In addition to validating the AI tool, this study will also provide observational data concerning its use to assess the pathway execution in real-world performance. RESULTS: The study is currently recruiting participants at multiple centres within the United Kingdom and is at the stage of collecting data. CONCLUSION: This standard diagnostic accuracy study carries no additional risk to patients as it does not affect the standard care pathway, and hence patient care remains unaffected.

The meniscal tear outcome (METRO) review: A systematic review summarising the clinical course and outcomes of patients with a meniscal tear.

BACKGROUND: Meniscal tears affect 222 per 100,000 of the population and can be managed non-operatively or operatively with an arthroscopic partial meniscectomy (APM), meniscal repair or meniscal transplantation. The purpose of this review is to summarise the outcomes following treatment with a meniscal tear and explore correlations between outcomes. METHOD: A systematic review was performed of MEDLINE, EMBASE, AMED and the Cochrane Central Register of Controlled Trials to identify prospective studies describing the outcomes of patients with a meniscal tear. Comparisons were made of outcomes between APM and non-operative groups. Outcomes were graphically presented over time for all treatment interventions. Pearson's correlations were calculated between outcome timepoints. RESULTS: 35 studies were included, 28 reported outcomes following APM; four following meniscal repair and three following meniscal transplant. Graphical plots demonstrated a sustained improvement for all treatment interventions. A moderate to very strong correlation was reported between baseline and three-month outcomes. In the medium term, there was small significant difference in outcome between APM and non-operative measures (SMD 0.17; 95 % CI 0.04, 0.29), however, this was not clinically significant. CONCLUSIONS: Patients with a meniscal tear demonstrated a sustained initial improvement in function scores, which was true of all treatments examined. APM may have little benefit in older people, however, previous trials did not include patients who meet the current indications for surgery as a result the findings should not be generalised to all patients with a meniscal tear. Further trials are required in patients who meet current operative indications.

Randomised controlled trial comparing intraoperative cell salvage and autotransfusion with standard care in the treatment of hip fractures: a protocol for the WHITE 9 study.

INTRODUCTION: People who sustain a hip fracture are typically elderly, frail and require urgent surgery. Hip fracture and the urgent surgery is associated with acute blood loss, compounding patients' pre-existing comorbidities including anaemia. Approximately 30% of patients require a donor blood transfusion in the perioperative period. Donor blood transfusions are associated with increased rates of infections, allergic reactions and longer lengths of stay. Furthermore, there is a substantial cost associated with the use of donor blood. Cell salvage and autotransfusion is a technique that recovers, washes and transfuses blood lost during surgery back to the patient. The objective of this study is to determine the clinical and cost effectiveness of intraoperative cell salvage, compared with standard care, in improving health related quality-of-life of patients undergoing hip fracture surgery. METHODS AND ANALYSIS: Multicentre, parallel group, two-arm, randomised controlled trial. Patients aged 60 years and older with a hip fracture treated with surgery are eligible. Participants will be randomly allocated on a 1:1 basis to either undergo cell salvage and autotransfusion or they will follow the standard care pathway. Otherwise, all care will be in accordance with the National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in the primary endpoint: EuroQol-5D-5L HRQoL at 4 months post injury. Secondary outcomes will include complications, postoperative delirium, residential status, mobility, allogenic blood use, mortality and resource use. ETHICS AND DISSEMINATION: NHS ethical approval was provided on 14 August 2019 (19/WA/0197) and the trial registered (ISRCTN15945622). After the conclusion of this trial, a manuscript will be prepared for peer-review publication. Results will be disseminated in lay form to participants and the public. TRIAL REGISTRATION NUMBER: ISRCTN15945622.

Subacromial balloon spacer for irreparable rotator cuff tears of the shoulder (START:REACTS): a group-sequential, double-blind, multicentre randomised controlled trial.

BACKGROUND: New surgical procedures can expose patients to harm and should be carefully evaluated before widespread use. The InSpace balloon (Stryker, USA) is an innovative surgical device used to treat people with rotator cuff tears that cannot be repaired. We aimed to determine the effectiveness of the InSpace balloon for people with irreparable rotator cuff tears. METHODS: We conducted a double-blind, group-sequential, adaptive randomised controlled trial in 24 hospitals in the UK, comparing arthroscopic debridement of the subacromial space with biceps tenotomy (debridement only group) with the same procedure but including insertion of the InSpace balloon (debridement with device group). Participants had an irreparable rotator cuff tear, which had not resolved with conservative treatment, and they had symptoms warranting surgery. Eligibility was confirmed intraoperatively before randomly assigning (1:1) participants to a treatment group using a remote computer system. Participants and assessors were masked to group assignment. Masking was achieved by using identical incisions for both procedures, blinding the operation note, and a consistent rehabilitation programme was offered regardless of group allocation. The primary outcome was the Oxford Shoulder Score at 12 months. Pre-trial simulations using data from early and late timepoints informed stopping boundaries for two interim analyses. The primary analysis was on a modified intention-to-treat basis, adjusted for the planned interim analysis. The trial was registered with ISRCTN, ISRCTN17825590. FINDINGS: Between June 1, 2018, and July 30, 2020, we assessed 385 people for eligibility, of which 317 were eligible. 249 (79%) people consented for inclusion in the study. 117 participants were randomly allocated to a treatment group, 61 participants to the debridement only group and 56 to the debridement with device group. A predefined stopping boundary was met at the first interim analysis and recruitment stopped with 117 participants randomised. 43% of participants were female, 57% were male. We obtained primary outcome data for 114 (97%) participants. The mean Oxford Shoulder Score at 12 months was 34·3 (SD 11·1) in the debridement only group and 30·3 (10·9) in the debridement with device group (mean difference adjusted for adaptive design -4·2 [95% CI -8·2 to -0·26];p=0·037) favouring control. There was no difference in adverse events between the two groups. INTERPRETATION: In an efficient, adaptive trial design, our results favoured the debridement only group. We do not recommend the InSpace balloon for the treatment of irreparable rotator cuff tears. FUNDING: Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health and Care Research partnership.

Inter and Intraobserver Agreement of the IOOG SAMEO ATO Classification for Tympanomastoid Surgery.

INTRODUCTION: In 2018 the International Otology Outcome Group (IOOG) introduced the stage of surgery, approach, mastoidectomy, external ear canal reconstruction, obliteration of mastoid cavity, access to middle ear, tympanic membrane, ossicular chain (SAMEO ATO) categorization framework for tympanomastoid surgery to develop a classification system that encompasses all aspects of surgical technique that are likely to influence the outcome of tympanomastoid surgery. To date there is no study that examines inter or intraobserver reliability of this classification system. OBJECTIVE: To assess inter and intraobserver reliability of the SAMEO ATO classification. STUDY DESIGN AND SETTING: Retrospective single center study. INTERVENTION: Two observers independently categorized 167 tympanomastoid surgeries using the SAMEO-ATO system to allow for interobserver analysis. Categorization was performed retrospectively from operation notes. Intraobserver reliability was evaluated for one observer. PATIENTS: One hundred sixty seven tympanomastoid surgeries performed by a single surgeon between 2018 and 2021. MAIN OUTCOME MEASURE: Inter and intraobserver reliability calculated using Cohen's kappa. RESULTS: Almost perfect interobserver agreement was seen for stage of surgery ( S ), approach ( A ), mastoidectomy ( M ), and ossicular chain ( O ) with kappa scores ranging from of 0.957 to 0.848.Almost perfect intraobserver agreement was seen for approach ( A ), mastoidectomy ( M ), external ear reconstruction ( E ), obliteration of mastoid cavity ( O ), access to middle ear ( A ), and ossicular chain ( O ) with kappa ranging from 0.929 to 08.21. CONCLUSION: The SAMEO ATO classification is a reliable system for recording surgical procedures. Given the complexity of the SAMEO ATO classification it is vital that those using it have a thorough knowledge of the classification.

Moulded cast compared with K-wire fixation after manipulation of an acute dorsally displaced distal radius fracture: the DRAFFT 2 RCT.

BACKGROUND: Patients with a displaced fracture of the distal radius are frequently offered surgical fixation. Manipulation of the fracture and moulded plaster casting is an alternative treatment that avoids metal implants, but evidence of its effectiveness is lacking. OBJECTIVE: To compare functional outcomes, quality-of-life outcomes, complications and resource use among patients with a dorsally displaced fracture of the distal radius treated with manipulation and surgical fixation with Kirschner wires (K-wires) and those treated with manipulation and moulded cast. DESIGN: Pragmatic, superiority, multicentre, randomised controlled trial with a health economic evaluation. SETTING: A total of 36 orthopaedic trauma centres in the UK NHS. PARTICIPANTS: Patients (aged ≥ 16 years) treated for an acute dorsally displaced fracture of the distal radius were potentially eligible. Patients were excluded if their injury had occurred > 2 weeks previously, if the fracture was open, if it extended > 3 cm from the radiocarpal joint or if it required open reduction, or if the participant was unable to complete questionnaires. INTERVENTIONS: Participants were randomly assigned in theatre (1 : 1) to receive a moulded cast (i.e. the cast group) or surgical fixation with K-wires (i.e. the K-wire group) after fracture manipulation. MAIN OUTCOME MEASURES: The primary outcome measure was the Patient-Rated Wrist Evaluation score at 12 months, analysed on an intention-to-treat basis. Health-related quality of life was recorded using the EuroQol-5 Dimensions, five-level version, and resource use was recorded from a health and personal social care perspective. RESULTS: Between January 2017 and March 2019, 500 participants (mean age 60 years, 83% women) were randomly allocated to receive a moulded cast (n = 255) or surgical fixation with K-wire (n = 245) following a manipulation of their fracture. A total of 395 (80%) participants were included in the primary analysis at 12 months. There was no difference in the Patient-Rated Wrist Evaluation score at 1 year post randomisation [cast group: n = 200, mean score 21.2 (standard deviation 23.1); K-wire group: n = 195, mean score 20.7 (standard deviation 22.3); adjusted mean difference -0.34 (95% confidence interval -4.33 to 3.66); p = 0.87]. A total of 33 (13%) participants in the cast group required surgical fixation for loss of fracture position in the first 6 weeks, compared with one participant in the K-wire group (odds ratio 0.02, 95% confidence interval 0.001 to 0.10). The base-case cost-effectiveness analysis showed that manipulation and surgical fixation with K-wires had a higher mean cost than manipulation and a moulded cast, despite similar mean effectiveness. The use of K-wires is unlikely to be cost-effective, and sensitivity analyses found this result to be robust. LIMITATIONS: Because the interventions were identifiable, neither patients nor clinicians could be blind to their treatment. CONCLUSIONS: Surgical fixation with K-wires was not found to be superior to moulded casting following manipulation of a dorsally displaced fracture of the distal radius, as measured by Patient-Rated Wrist Evaluation score. However, one in eight participants treated in a moulded cast required surgery for loss of fracture reduction in the first 6 weeks. After a successful closed reduction, clinicians may consider a moulded cast as a safe and cost-effective alternative to surgical fixation with K-wires. FUTURE WORK: Further research should focus on optimal techniques for immobilisation and manipulation of this type of fracture, including optimal analgesia, and for rehabilitation of the patient after immobilisation. TRIAL REGISTRATION: This trial is registered as ISRCTN11980540 and UKCRN Portfolio 208830. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 11. See the NIHR Journals Library website for further project information.

Many patients with a wrist fracture can be treated with a simple cast or splint. However, if the broken bones have moved out of position, patients are frequently offered a manipulation of the fracture to restore the position of the broken bones. The bones may then be held in place with metal implants while they heal. A moulded plaster cast, shaped to support the bones, is an alternative treatment that avoids metal implants, but there is little research to suggest which treatment is better. The Distal Radius Acute Fracture Fixation Trial 2 (DRAFFT 2) study compared surgical fixation with metal wires with a moulded cast for patients with a broken wrist. Half of the patients underwent surgical fixation and half were given the moulded cast. The decision about which treatment patients were given was made by chance using a computer to ensure a fair comparison. The patients in both groups described their own wrist function and quality of life in the first year after their treatment and these descriptions were compared. A total of 500 patients took part at 36 NHS hospitals in the UK. The patients treated with a moulded cast reported very similar wrist function and quality of life to that of the patients treated with surgical fixation. However, one in eight patients treated with the moulded cast later required surgery because their broken bones had fallen back out of position. This study showed that a moulded cast is as good as, but costs less than, surgical fixation for patients with a broken wrist in terms of wrist function. However, a small proportion of the patients treated with a moulded cast may require later surgery if the broken bones cannot be held in position by the cast alone.

Functional connectivity during feedback learning in smokers.

BACKGROUND: Although it has been traditionally assumed that dysregulation of psychological processes in smokers results from activity within specific brain regions, an emerging view regards such dysregulation as attributable to aberrant communication between distinct brain regions. These processes can be measured during appropriate task paradigms such as the learning from errors task. This study aims to elucidate interactions between brain regions underlying the process of learning from errors, punishment and sensitivity to reward in dependent smokers. METHODS: Functional MRI data from 23 age-matched dependent smokers (8 females, mean age = 25.48, SD = 4.46) and 23 controls (13 females, mean age = 24.83, SD = 5.99) were analysed during a feedback-based associative learning task. Functional connectivity between the dorsal anterior cingulate cortex, nucleus accumbens and reward/sensorimotor areas was investigated during a feedback learning task. RESULTS: Behaviourally, smokers exhibited lower error correction rates and were less sensitive to punishment magnitude. Smokers showed increased functional connectivity between dorsal anterior cingulate cortex/nucleus accumbens seed regions and numerous reward-related target regions including the putamen, anterior cingulate and orbitofrontal cortex. CONCLUSIONS: Reduced learning from errors and widespread aberrant functional connectivity contribute to the emerging functional characterisation of dependent smokers and may bear significant implications when considering the efficacy of smoking interventions.

Meniscal tears are more common than previously identified, however, less than a quarter of people with a tear undergo arthroscopy.

PURPOSE: The management of meniscal tears is a widely researched and evolving field. Previous studies reporting the incidence of meniscal tears are outdated and not representative of current practice. The aim of this study was to report the current incidence of MRI confirmed meniscal tears in patients with a symptomatic knee and the current intervention rate in a large NHS trust. METHODS: Radiology reports from 13,358 consecutive magnetic resonance imaging scans between 2015 and 2017, performed at a large UK hospital serving a population of 470,000, were assessed to identify patients with meniscal tears. The hospital database was interrogated to explore the subsequent treatment undertaken by the patient. A linear regression model was used to identify if any factors predicted subsequent arthroscopy. RESULTS: 1737 patients with isolated meniscal tears were identified in patients undergoing an MRI for knee pain, suggesting a rate of 222 MRI confirmed tears per 100,000 of the population aged 18 to 55 years old. 47% attended outpatient appointments and 22% underwent arthroscopy. Root tears [odds ratio (95% CI) 2.24 (1.0, 4.49); p = 0.049] and bucket handle tears were significantly associated with subsequent surgery, with no difference between the other types of tears. The presence of chondral changes did not significantly affect the rate of surgery [0.81 (0.60, 1.08); n.s]. CONCLUSION: Meniscal tears were found to be more common than previously described. However, less than half present to secondary care and only 22% undergo arthroscopy. These findings should inform future study design and recruitment strategies. In agreement with previous literature, bucket handle tears and root tears were significant predictors of subsequent surgery. LEVEL OF EVIDENCE: III.

Meniscal Tear Outcome (METRO) review: a protocol for a systematic review summarising the clinical course and patient experiences of meniscal tears in the current literature.

INTRODUCTION: Meniscal tears are a common knee injury with an incidence of 60 per 100 000. Management of meniscal tears can include either non-operative measures or operative procedures such as arthroscopic partial meniscectomy (APM). Despite substantial research evaluating the effectiveness of APM in the recent past, little is known about the clinical course or the experiences of patients with a meniscal tear. AIM: To summarise the short to long-term patterns of variability in outcome in patients with a meniscal tear.To summarise the evidence on patient experiences of meniscal tears. In particular, we will focus on patient experiences of treatment options, treatment pathways and their views of the outcomes used in meniscal tear research. METHODS AND ANALYSIS: Two search strategies will be developed to identify citations from EMBASE, MEDLINE, AMED, CENTRAL, Web of Science and Sociofile. The date of our planned search is 14 August 2020. For the quantitative review we will identify studies reporting patient-reported outcome measures in patients after a meniscal tear. The standardised mean change will be used to assess the variation in size of response and summarise the overall response to each treatment option. All studies will undergo quality assessment using either the Cochrane risk of bias or the Newcastle-Ottawa tool.A qualitative systematic review will be used to identify studies reporting views and experiences of patients with a meniscal tear. All studies will be assessed using the Critical Appraisal Skills Programme tool and if sufficient data are present a meta-synthesis will be performed to identify first, second and third-order constructs. ETHICS AND DISSEMINATION: Given the nature of this study, no formal ethical approval will be sought. Results from the review will be disseminated at national conferences and will be submitted to a peer-reviewed journal for publication. Lay summaries will be freely available via the study Twitter page. PROSPERO REGISTRATION NUMBER: CRD42019122179.

Meniscal tear outcome Study (METRO Study): a study protocol for a multicentre prospective cohort study exploring the factors which affect outcomes in patients with a meniscal tear.

INTRODUCTION: This study is designed to explore the baseline characteristics of patients under 55 years of age with a meniscal tear, and to describe the relationship between the baseline characteristics and patient-reported outcome measures (PROMs) over 12 months. Research has highlighted the need for a trial to investigate the effectiveness of arthroscopic meniscectomy in younger patients. Before this trial, we need to understand the patient population in greater detail. METHODS AND ANALYSIS: This is a multicentre prospective cohort study. Participants aged between 18 and 55 years with an MRI confirmed meniscal tear are eligible for inclusion. Baseline characteristics including age, body mass index, gender, PROMs duration of symptoms and MRI will be collected. The primary outcome measure is the Western Ontario Meniscal Evaluation Tool at 12 months. Secondary outcome measures will include PROMs such as EQ5D, Knee Injury and Osteoarthritis Outcome Score and patient global impression of change score at 3, 6 and 12 months. ETHICS AND DISSEMINATION: The study obtained approval from the National Research Ethics Committee West Midlands-Black Country research ethics committee (19/WM/0079) on 12 April 2019. The study is sponsored by the University of Warwick. The results will be disseminated via peer-reviewed publication. TRIAL REGISTRATION NUMBER: UHCW R&D Reference: IA428119. University of Warwick Sponsor ID: SC.08/18-19.

Protocol for a randomised controlled trial of Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS).

INTRODUCTION: Shoulder pain due to irreparable rotator cuff tears can cause substantial disability, but treatment options are limited. A balloon spacer is a relatively simple addition to a standard arthroscopic debridement procedure, but it is costly and there is no current randomised trial evidence to support its use. This trial will evaluate the clinical and cost-effectiveness of a subacromial balloon spacer for individuals undergoing arthroscopic debridement for irreparable rotator cuff tears.New surgical procedures can provide substantial benefit to patients. Good quality randomised controlled trials (RCTs) are needed, but trials in surgery are typically long and expensive, exposing patients to risk and the healthcare system to substantial costs. One way to improve the efficiency of trials is with an adaptive sample size. Such methods are well established in drug trials but have rarely, if ever, been used in surgical trials. METHODS AND ANALYSIS: Subacromial spacer for Tears Affecting Rotator cuff Tendons: a Randomised, Efficient, Adaptive Clinical Trial in Surgery (START:REACTS) is a participant and assessor blinded, adaptive, multicentre RCT comparing arthroscopic debridement with the InSpace balloon (Stryker, USA) to arthroscopic debridement alone for people with a symptomatic irreparable rotator cuff tear. It uses a group sequential adaptive design where interim analyses are performed using all of the 3, 6 and 12-month data that are available at each time point. A maximum of 221 participants will be randomised (1:1 ratio), this will provide 90% power (at the 5% level) for a 6 point difference in the primary outcome; the Oxford Shoulder Score at 12 months. A substudy will use deltoid-active MRI scans in 56 participants to assess the function of the balloon. Analysis will be on an intention-to-treat basis and reported according to principles established in the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: NRES number 18/WM/0025. The results will be disseminated via peer-reviewed publications, presentations at conferences, lay summaries and social media. TRIAL REGISTRATION NUMBER: ISRCTN17825590.

Adaptive seamless clinical trials using early outcomes for treatment or subgroup selection: Methods, simulation model and their implementation in R.

Adaptive seamless designs combine confirmatory testing, a domain of phase III trials, with features such as treatment or subgroup selection, typically associated with phase II trials. They promise to increase the efficiency of development programmes of new drugs, for example, in terms of sample size and/or development time. It is well acknowledged that adaptive designs are more involved from a logistical perspective and require more upfront planning, often in the form of extensive simulation studies, than conventional approaches. Here, we present a framework for adaptive treatment and subgroup selection using the same notation, which links the somewhat disparate literature on treatment selection on one side and on subgroup selection on the other. Furthermore, we introduce a flexible and efficient simulation model that serves both designs. As primary endpoints often take a long time to observe, interim analyses are frequently informed by early outcomes. Therefore, all methods presented accommodate interim analyses informed by either the primary outcome or an early outcome. The R package asd, previously developed to simulate designs with treatment selection, was extended to include subgroup selection (so-called adaptive enrichment designs). Here, we describe the functionality of the R package asd and use it to present some worked-up examples motivated by clinical trials in chronic obstructive pulmonary disease and oncology. The examples both illustrate various features of the R package and provide insights into the operating characteristics of adaptive seamless studies.

Platelet rich plasma versus placebo for the management of Achilles tendinopathy: protocol for the UK study of Achilles tendinopathy management (ATM) multi-centre randomised trial.

INTRODUCTION: In the UK, 150 000 people every year experience mid-substance Achilles tendinopathy. Typically patients are offered a range of treatment options such as exercise, electrotherapy, injections and surgery. With large variations in current practice, there is a pressing need to establish which treatments are effective and which are not. This is the protocol for a multi-centre randomised trial of platelet rich plasma (PRP) versus placebo injection for patients with Achilles tendinopathy. METHODS AND ANALYSIS: Adult patients with mid-substance Achilles tendinopathy for longer than 3 months will be screened. Randomisation will be on a 1:1 basis, stratified by centre and bilateral presentation. Participants will be allocated to either a single PRP injection or placebo injection. A minimum of 240 patients will be recruited into the study; this number will provide 90% power to detect a difference of 12 points in Victorian Institute of Sport Assessment-Achilles score at 6 months. Quality of life, pain and complications data will be collected at baseline, 2-week, 3-month and 6-month post-randomisation. The differences between treatment groups will be assessed on an intention-to-treat basis. ETHICS, REGISTRATION AND DISSEMINATION: This trial was funded by Versus Arthritis and commenced on 1 September 2015 (Versus Arthritis 20831). National Research Ethic Committee approved this study on 30 October 2015 (15/WM/0359). It was registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry with reference number ISRCTN 13254422 on 28 October 2015. The first site opened to recruitment on 27 April 2016 and the trial was in active recruitment at the point of submitting the protocol paper. The results of this trial will be submitted to a peer-reviewed journal and will inform clinical practice with regard to the treatment of Achilles tendinopathy.

Randomised controlled trial comparing hydroxyapatite coated uncemented hemiarthroplasty with cemented hemiarthroplasty for the treatment of displaced intracapsular hip fractures: a protocol for the WHITE 5 study.

INTRODUCTION: Hip fracture is a serious injury in adults, especially those aged over 60 years. The most common type of hip fracture (displaced intracapsular) is treated for the majority of patients with a partial hip replacement (hemiarthroplasty). The hemiarthroplasty implant can be fixed to the bone with or without bone cement. Cement is the current recommended technique but recently some risks have been identified, which could potentially be avoided by using uncemented implants. Controversy, therefore, remains about which type of hemiarthroplasty offers patients the best outcomes.This is the protocol for a multicentre randomised controlled trial comparing cemented hemiarthroplasty versus uncemented hemiarthroplasty for patients 60 years and over with a displaced intracapsular hip fracture. METHODS AND ANALYSIS: Multicentre (a minimum of seven UK hospitals), multisurgeon, parallel group, two-arm, superiority, randomised controlled trial. Patients aged 60 years and older with a displaced intracapsular hip fracture treated with hemiarthroplasty surgery are eligible. Participants will be randomly allocated on a 1:1 basis to either a cemented hemiarthroplasty or a modern hydroxyapatite coated uncemented hemiarthroplasty. Otherwise all care will be in accordance with the National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in the primary endpoint: health-related quality of life (EuroQol 5 dimensions 5 levels) at 4 months postinjury. The treatment effect will be estimated using a two-sided t-test adjusted for age, gender and cognitive impairment based on an intention-to-treat analysis. Secondary outcomes include mortality, complications including revision surgery and cause, mobility status, residential status, health-related quality of life at 1 and 12 months and health resource use. A within-trial economic analysis will be conducted. ETHICS, DISSEMINATION AND FUNDING: Wales Research Ethics Committee 5 approved the feasibility phase on 2 December 2016 (16/WA/0351) and the definitive trial on 22 November 2017 (17/WA/0383). This study is sponsored by the University of Oxford and funded by the National Institute for Health Research, Research for Patient Benefit (PB-PG-0215-36043 and PB-PG-1216-20021). A manuscript for a peer-reviewed journal will be prepared and the results shared with patients via local mechanisms at participating centres. TRIAL REGISTRATION NUMBER: ISRCTN18393176.

Communicating benign biopsy results by telephone in the NHS Breast Screening Programme: a protocol for a cluster randomised crossover trial.

INTRODUCTION: One of the main harms from breast cancer screening is the anxiety caused by false positive results. Various factors may be associated with false-positive anxiety. One modifiable factor may be the method of communication used to deliver results. The aim of this study is to measure the effect on anxiety of receiving benign biopsy results in-person or by telephone. METHODS AND ANALYSIS: This is a multi-centre cluster randomised crossover trial in the English National Health Service Breast Screening Programme (NHSBSP) involving repeated survey measures at four time points. Participants will be women of screening age who have a biopsy following a suspicious mammography result, who ultimately receive a benign or normal (B1) result. Centres will trial both telephone and in-person results on a month-by-month basis, being randomised to which communication method will be trialled first. Women will be blinded to the method of communication they will receive. The analysis will compare women who have received telephone results and women who have received in-person results. The primary outcome measure will be anxiety (measured by the Psychological Consequences Questionnaire) after receiving results, while controlling for baseline anxiety. Secondary outcome measures will include anxiety at 3 and 6 months post-results, understanding of results and patient preferences for how results are communicated. Qualitative telephone interviews will also be conducted to further explore women's reasons for communication preferences. Qualitative and quantitative data will be integrated after initial separate analysis using the pillar integration process. ETHICS AND DISSEMINATION: This study has been approved by the Public Health England Breast Screening Programme Research Advisory Committee, (BSPRAC_0013, ODR1718_040) and the National Health Service Health Research Authority (HRA) West Midlands-Coventry & Warwickshire Research Ethics Committee (17/WM/0313). The findings from this study will be disseminated to key stakeholders within the NHSBSP and via academic publications. TRIAL REGISTRATION NUMBER: ISRCTN36997684 TRIAL SPONSOR: This research is part of a PhD award and is funded by the Economic and Social Research Council Doctoral Training Centre at the University of Warwick and Public Health England. The sponsor for this research is Jane Prewett (sponsorship@warwick.ac.uk).

Adoption of a novel surgical innovation into clinical practice: protocol for a qualitative systematic review examining surgeon views.

INTRODUCTION: Efficient adoption of clinically effective novel surgical innovations has great potential benefits for patients. Factors affecting the adoption of surgical innovation are not well understood and proposed models of adoption do not accurately correlate with historical evidence. This protocol is for a systematic review that aims to identify the qualitative evidence relating to surgeon views regarding the adoption of novel surgical innovation into clinical practice. METHODS AND ANALYSIS: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance will be performed. Two independent reviewers will search the following databases: MEDLINE, Embase, Science Direct, Scopus, Web of Science and the Cochrane Library of Systematic Reviews. Inclusion criteria are studies which report on the views of surgeons who adopt a novel surgical innovation into clinical practice. Each article will be screened for inclusion and assessed according to a Critical Appraisal Skills Programme tool. Data will be synthesised and analysed according to thematic analysis. Given the anticipated yield of a small heterogeneous body of evidence meeting the eligibility criteria for the review, a narrative-based summary is planned. ETHICS AND DISSEMINATION: This review does not require formal ethical approval as it does not involve direct patient contact or patient-identifiable data. The results of this review will be published in a peer-reviewed journal and presented at relevant conferences. The results will also inform an empirical qualitative study exploring surgeon and other stakeholder views regarding the introduction of novel surgical technology and procedures into clinical practice. PROSPERO REGISTRATION NUMBER: CRD42017076715.

Comparison of hip function and quality of life of total hip arthroplasty and resurfacing arthroplasty in the treatment of young patients with arthritis of the hip joint at 5 years.

OBJECTIVE: To compare the medium-term clinical effectiveness of total hip arthroplasty and resurfacing arthroplasty. DESIGN: Single centre, two-arm, parallel group, assessor blinded, randomised controlled trial with 1:1 treatment allocation. SETTING: A large teaching hospital in England. PARTICIPANTS: 122 patients older than 18 years with severe arthritis of the hip joint, suitable for resurfacing arthroplasty of the hip. Patients were excluded if they were considered to be unable to adhere to trial procedures or complete questionnaires. INTERVENTIONS: Total hip arthroplasty (replacement of entire femoral head and neck); hip resurfacing arthroplasty (replacement of the articular surface of femoral head only, femoral neck remains intact). Both procedures replaced the articular surface of the acetabulum. OUTCOMES: The outcome measures were hip function assessed using the Oxford Hip Score (OHS) and health-related quality of life assessed using the EuroQol (EQ-5D). Patients were followed up annually for a minimum of 5 years. Outcome data were modelled using the generalised estimating equation methodology to explore temporal variations during follow-up. RESULTS: 60 patients were randomly assigned to hip resurfacing arthroplasty and 62 to total hip arthroplasty. 95 (78%) of the 122 original study participants provided data at 5 years. There was a small decrease in both hip functions and quality of life in both groups of patients each year during the 5-year follow-up period. However, there was no evidence of a significant difference between treatments group in the OHS (P=0.333) or the EQ-5D (P=0.501). CONCLUSIONS: We previously reported no difference in outcome in the first year after surgery. The current medium-term results also show no evidence of a difference in hip function or health-related quality of life in the 5 years following a total hip arthroplasty versus resurfacing arthroplasty. TRIAL REGISTRATION NUMBER: ISRCTN33354155. UKCRN 4093.