Research priorities of members of the British Association for Surgery of the Knee.

Aims: This study aims to identify the top unanswered research priorities in the field of knee surgery using consensus-based methodology. Methods: Initial research questions were generated using an online survey sent to all 680 members of the British Association for Surgery of the Knee (BASK). Duplicates were removed and a longlist was generated from this scoping exercise by a panel of 13 experts from across the UK who provided oversight of the process. A modified Delphi process was used to refine the questions and determine a final list. To rank the final list of questions, each question was scored between one (low importance) and ten (high importance) in order to produce the final list. Results: This consensus exercise took place between December 2020 and April 2022. A total of 286 clinicians from the BASK membership provided input for the initial scoping exercise, which generated a list of 105 distinct research questions. Following review and prioritization, a longlist of 51 questions was sent out for two rounds of the Delphi process. A total of 42 clinicians responded to the first round and 24 responded to the second round. A final list of 24 research questions was then ranked by 36 clinicians. The topics included arthroplasty, infection, meniscus, osteotomy, patellofemoral, cartilage, and ligament pathologies. The management of early osteoarthritis was the highest-ranking question. Conclusion: A Delphi exercise involving the BASK membership has identified the future research priorities in knee surgery. This list of questions will allow clinicians, researchers, and funders to collaborate in order to deliver high-quality research in knee surgery and further advance the care provided to patients with knee pathology.

The clinical and cost-effectiveness of elective primary total knee replacement with PAtellar Resurfacing compared to selective patellar resurfacing: a pragmatic multicentre randomized controlled Trial (PART).

Aims: During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon's decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing. Methods: The PAtellar Resurfacing Trial (PART) is a patient- and assessor-blinded multicentre, pragmatic parallel two-arm randomized superiority trial of adults undergoing elective primary TKR for primary osteoarthritis at NHS hospitals in England, with an embedded internal pilot phase (ISRCTN 33276681). Participants will be randomly allocated intraoperatively on a 1:1 basis (stratified by centre and implant type (cruciate-retaining vs cruciate-sacrificing)) to always resurface or selectively resurface the patella, once the surgeon has confirmed sufficient patellar thickness for resurfacing and that constrained implants are not required. The primary analysis will compare the Oxford Knee Score (OKS) one year after surgery. Secondary outcomes include patient-reported outcome measures at three months, six months, and one year (Knee injury and Osteoarthritis Outcome Score, OKS, EuroQol five-dimension five-level questionnaire, patient satisfaction, postoperative complications, need for further surgery, resource use, and costs). Cost-effectiveness will be measured for the lifetime of the patient. Overall, 530 patients will be recruited to obtain 90% power to detect a four-point difference in OKS between the groups one year after surgery, assuming up to 40% resurfacing in the selective group. Conclusion: The trial findings will provide evidence about the clinical and cost-effectiveness of always patellar resurfacing compared to selective patellar resurfacing. This will inform future NICE guidelines on primary TKR and the role of selective patellar resurfacing.

Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol.

INTRODUCTION: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. METHODS AND ANALYSIS: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ISRCTN87336549.

What recovery domains are important following a total knee replacement? A qualitative, interview-based study.

OBJECTIVES: To explore people's views of recovery from total knee replacement (TKR) and which recovery domains they felt were important. DESIGN: Semi-structured interviews exploring the views of individuals about to undergo or who have undergone TKR. A constant-comparative approach with thematic analysis was used to identify themes. The process of sampling, collecting data and analysis were continuous and iterative throughout the study, with interviews ceasing once thematic saturation was achieved. SETTING: Tertiary care centre. PARTICIPANTS: A purposive sample was used to account for variables including pre, early or late postoperative status. RESULTS: 12 participants were interviewed, 4 who were preoperative, 4 early postoperative and 4 late postoperative. Themes of pain, function, fear of complications, awareness of the artificial knee joint and return to work were identified. Subthemes of balancing acute and chronic pain were identified. CONCLUSIONS: The results of this interview-based study identify pain and function, in particular mobility, that were universally important to those undergoing TKR. Surgeons should consider exploring these domains when taking informed consent to enhance shared decision-making. Researchers should consider these recovery domains when designing interventional studies.

Item Response Theory Validation of the Forgotten Joint Score for Persons Undergoing Total Knee Replacement.

BACKGROUND: The Forgotten Joint Score (FJS), a commonly used patient-reported outcome measure, was developed without fully confirming assumptions such as unidimensionality (all items reflect 1 underlying factor), appropriate weighting of each item in scoring, absence of differential item functioning (in which different groups, e.g., men and women, respond differently), local dependence (pairs of items are measuring only 1 underlying factor), and monotonicity (persons with higher function have a higher score). We applied item response theory (IRT) to perform validation of the FJS according to contemporary standards, and thus support its ongoing use. We aimed to confirm that the FJS reflects a single latent trait. In addition, we aimed to determine whether an IRT model could be fitted to the FJS. METHODS: Participants undergoing primary total knee replacement provided responses to the FJS items preoperatively and at 6 and 12 months postoperatively. An exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and Mokken analysis were conducted. A graded response model (GRM) was fitted to the data. RESULTS: A total of 1,774 patient responses were analyzed. EFA indicated a 1-factor model (all 12 items reflecting 1 underlying trait). CFA demonstrated an excellent model fit. Items did not have equal weighting. The FJS demonstrated good monotonicity and no differential item functioning by sex, age, or body mass index. GRM parameters are reported in this paper. CONCLUSIONS: The FJS meets key validity assumptions, supporting its use in clinical practice and research. The IRT-adapted FJS has potential advantages over the traditional FJS: it provides continuous measurements with finer granularity between health states, includes individual measurement error, and can compute scores despite more missing data (with only 1 response required to estimate a score). It can be applied retrospectively to existing data sets or used to deliver individualized computerized adaptive tests. LEVEL OF EVIDENCE: Prognostic Level II . See Instructions for Authors for a complete description of levels of evidence.

Robotic trials in arthroplasty surgery.

Total hip and knee arthroplasty (THA, TKA) are largely successful procedures; however, both have variable outcomes, resulting in some patients being dissatisfied with the outcome. Surgeons are turning to technologies such as robotic-assisted surgery in an attempt to improve outcomes. Robust studies are needed to find out if these innovations are really benefitting patients. The Robotic Arthroplasty Clinical and Cost Effectiveness Randomised Controlled Trials (RACER) trials are multicentre, patient-blinded randomized controlled trials. The patients have primary osteoarthritis of the hip or knee. The operation is Mako-assisted THA or TKA and the control groups have operations using conventional instruments. The primary clinical outcome is the Forgotten Joint Score at 12 months, and there is a built-in analysis of cost-effectiveness. Secondary outcomes include early pain, the alignment of the components, and medium- to long-term outcomes. This annotation outlines the need to assess these technologies and discusses the design and challenges when conducting such trials, including surgical workflows, isolating the effect of the operation, blinding, and assessing the learning curve. Finally, the future of robotic surgery is discussed, including the need to contemporaneously introduce and evaluate such technologies.

What's important for recovery after a total knee replacement? A systematic review of mixed methods studies.

BACKGROUND: Understanding how patients perceive and prioritise various aspects of recovery following total knee replacement, including pain, function and return to activity, will help clinicians in pre-operative consultations by ensuring they effectively address patient concerns and managing their expectations. AIMS: The aim of this study is to identify aspects of recovery that are important to people after a total knee replacement. METHODS: Studies were identified from Medline, Embase, PsycInfo, Cochrane Library and Web of Science. This mixed methods review included all original study types (quantitative, qualitative, discrete choice experiments and mixed methods design). Reviews and non-peer-reviewed publications were excluded. Studies with participants (age ≥ 18 years) who had a primary TKR for osteoarthritis were included. Studies of people with unicompartmental knee, patella-femoral or revision knee replacement were excluded. Recovery attributes were extracted from individual papers and grouped into recovery themes. RESULTS: A total of 23 studies with 8404 participants and 18 recovery themes were developed. The most frequently identified overarching theme was pain, followed by activities of daily living, mobility (walking), recreational activities, specific functional movements of the knee, use of walking aids, sexual activity and range of motion of the knee. Medical complications were an infrequently reported theme, however, was deemed to be high importance. CONCLUSIONS: Reducing pain, returning of activities and daily living and mobility are the three most frequently reported recovery domains for people after TKR. Clinicians should be aware of recovery themes, to ensure they are explored sufficiently when consenting for a TKR. Future research should aim to determine the relative importance of these attributes compared to each other. Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253699.

UK robotic arthroplasty clinical and cost effectiveness randomised controlled trial for hips (RACER-Hip): a study protocol.

INTRODUCTION: The number of robotic-assisted hip replacement procedures has expanded globally with the intended aim of improving outcomes. Intraoperative robotic-arm systems add additional costs to total hip replacement (THR) surgery but may improve surgical precision and could contribute to diminished pain and improved function. Additionally, these systems may reduce the need for expensive revision surgery. Surgery with conventional instruments may be just as successful, quick and affordable. There is timely demand for a robust evaluation of this technology. METHODS AND ANALYSIS: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial for Hips (RACER-Hip) is a multicentre (minimum of six UK sites), participant-assessor blinded, randomised controlled trial. 378 participants with hip osteoarthritis requiring THR will be randomised (1:1) to receive robotic-assisted THR, or THR using conventional surgical instruments. The primary outcome is the Forgotten Joint Score at 12 months post-randomisation; a patient-reported outcome measure assessing participants' awareness of their joint when undertaking daily activities. Secondary outcomes will be collected post-operatively (pain, blood loss and opioid usage) and at 3, 6, 12, 24 months, then 5 and 10 years postrandomisation (including function, pain, health-related quality of life, reoperations and satisfaction). Allocation concealment will be accomplished using a computer-based randomisation procedure on the day of surgery. Blinding methods include the use of sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will adhere to Consolidated Standards of Reporting Trials statements. ETHICS AND DISSEMINATION: The trial was approved by an ethics committee (Solihull Research Ethics Committee, 30 June 2021, IRAS: 295831). Participants will provide informed consent before agreeing to participate. Results will be disseminated using peer-reviewed journal publications, presentations at international conferences and through the use of social media. We will develop plans to disseminate to patients and public with our patient partners. TRIAL REGISTRATION NUMBER: ISRCTN13374625.

Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial (RACER-knee): a study protocol.

INTRODUCTION: Robotic-assisted knee replacement systems have been introduced to healthcare services worldwide in an effort to improve clinical outcomes for people, although high-quality evidence that they are clinically, or cost-effective remains sparse. Robotic-arm systems may improve surgical accuracy and could contribute to reduced pain, improved function and lower overall cost of total knee replacement (TKR) surgery. However, TKR with conventional instruments may be just as effective and may be quicker and cheaper. There is a need for a robust evaluation of this technology, including cost-effectiveness analyses using both within-trial and modelling approaches. This trial will compare robotic-assisted against conventional TKR to provide high-quality evidence on whether robotic-assisted knee replacement is beneficial to patients and cost-effective for healthcare systems. METHODS AND ANALYSIS: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial-Knee is a multicentre, participant-assessor blinded, randomised controlled trial to evaluate the clinical and cost-effectiveness of robotic-assisted TKR compared with TKR using conventional instruments. A total of 332 participants will be randomised (1:1) to provide 90% power for a 12-point difference in the primary outcome measure; the Forgotten Joint Score at 12 months postrandomisation. Allocation concealment will be achieved using computer-based randomisation performed on the day of surgery and methods for blinding will include sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will be reported in line with the Consolidated Standards of Reporting Trials statement. A parallel study will collect data on the learning effects associated with robotic-arm systems. ETHICS AND DISSEMINATION: The trial has been approved by an ethics committee for patient participation (East Midlands-Nottingham 2 Research Ethics Committee, 29 July 2020. NRES number: 20/EM/0159). All results from the study will be disseminated using peer-reviewed publications, presentations at international conferences, lay summaries and social media as appropriate. TRIAL REGISTRATION NUMBER: ISRCTN27624068.

Bone bridge technique for lateral meniscal allograft transplantation: no difference in clinical outcome compared to the soft tissue technique.

PURPOSE: There is considerable debate regarding the optimal method of fixation for lateral meniscus allograft transplantation (MAT), with bone bridge techniques technically harder but allowing maintenance of root attachments, while soft tissue techniques are potentially more challenging for healing. The aim of this study was to compare the clinical results of the bone bridge and soft tissue techniques for lateral MAT in terms of failure, re-operation rate, complications and patient reported outcomes. METHODS: Retrospective analysis of prospectively collected data for patients undergoing primary lateral MAT with a minimum of 12-month follow-up. Patients following surgery utilising the bone bridge technique (BB) were compared with historical control patients who underwent MAT with the soft tissue technique (ST). Outcome was assessed by failure rate, defined as removal or revision of the meniscus transplant, survivorship by Kaplan-Meir analysis, re-operation rates, and other adverse event. Patient-reported outcome measures (PROMs) were compared using data at the 2-year point or 1 year if not reached 2 years. RESULTS: One-hundred and twelve patients following lateral meniscal transplants were included, 31 in the BB group and 81 in the ST historical control group, with no differences in demographics between both groups. Median follow-up for the BB group was 18 (12-43) months compared to 46 (15-62) months for the ST group. There were 3 failures (9.6%) in the BB group v 2 (2.4%) in the ST group (n.s.) with a mean time to failure of 9 months in both groups. 9 patients (29%) required a re-operation (all cause) in the BB group v 24 patients (29.6%) in the ST group (n.s). There was no difference in complications between both groups. There was significant improvement (p < 0.0001) in all PROMs (Tegner, IKDC, KOOS and Lysholm) between baseline and 2-year follow-up for both groups but no between-group differences. CONCLUSION: Lateral MAT has a high success rate for symptomatic meniscal deficiency with significant benefits irrespective of the fixation technique. There is no advantage in performing the more technically demanding BB technique over ST fixation. LEVEL OF EVIDENCE: Level 2.

Surgical versus non-surgical interventions for treating patellar dislocation.

BACKGROUND: Patellar (knee cap) dislocation occurs when the patella disengages completely from the trochlear (femoral) groove. It affects up to 42/100,000 people, and is most prevalent in those aged 20 to 30 years old. It is uncertain whether surgical or non-surgical treatment is the best approach. This is important as recurrent dislocation occurs in up to 40% of people who experience a first time (primary) dislocation. This can reduce quality of life and as a result people have to modify their lifestyle. This review is needed to determine whether surgical or non-surgical treatment should be offered to people after patellar dislocation. OBJECTIVES: To assess the effects (benefits and harms) of surgical versus non-surgical interventions for treating people with primary or recurrent patellar dislocation. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, AMED, CINAHL, Physiotherapy Evidence Database and trial registries in December 2021. We contacted corresponding authors to identify additional studies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled clinical trials evaluating surgical versus non-surgical interventions for treating primary or recurrent lateral patellar dislocation in adults or children. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent patellar dislocation, and patient-rated knee and physical function scores. Our secondary outcomes were health-related quality of life, return to former activities, knee pain during activity or at rest, adverse events, patient-reported satisfaction, patient-reported knee instability symptoms and subsequent requirement for knee surgery. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 10 studies (eight randomised controlled trials (RCTs) and two quasi-RCTs) of 519 participants with patellar dislocation. The mean ages in the individual studies ranged from 13.0 to 27.2 years. Four studies included children, mainly adolescents, as well as adults; two only recruited children. Study follow-up ranged from one to 14 years. We are unsure of the evidence for all outcomes in this review because we judged the certainty of the evidence to be very low. We downgraded each outcome by three levels. Reasons included imprecision (when fewer than 100 events were reported or the confidence interval (CI) indicated appreciable benefits as well as harms), risk of bias (when studies were at high risk of performance, detection and attrition bias), and inconsistency (in the event that pooled analysis included high levels of statistical heterogeneity). We are uncertain whether surgery lowers the risk of recurrent dislocation following primary patellar dislocation compared with non-surgical management at two to nine year follow-up. Based on an illustrative risk of recurrent dislocation in 348 people per 1000 in the non-surgical group, we found that 157 fewer people per 1000 (95% CI 209 fewer to 87 fewer) had recurrent dislocation between two and nine years after surgery (8 studies, 438 participants). We are uncertain whether surgery improves patient-rated knee and function scores. Studies measured this outcome using different scales (the Tegner activity scale, Knee Injury and Osteoarthritis Outcome Score, Lysholm, Kujala Patellofemoral Disorders score and Hughston visual analogue scale). The most frequently reported score was the Kujala Patellofemoral Disorders score. This indicated people in the surgical group had a mean score of 5.73 points higher at two to nine year follow-up (95% CI 2.91 lower to 14.37 higher; 7 studies, 401 participants). On this 100-point scale, higher scores indicate better function, and a change score of 10 points is considered to be clinically meaningful; therefore, this CI includes a possible meaningful improvement. We are uncertain whether surgery increases the risk of adverse events. Based on an assumed risk of overall incidence of complications during the first two years in 277 people out of 1000 in the non-surgical group, 335 more people per 1000 (95% CI 75 fewer to 723 more) had an adverse event in the surgery group (2 studies, 144 participants). Three studies (176 participants) assessed participant satisfaction at two to nine year follow-up, reporting little difference between groups. Based on an assumed risk of 763 per 1000 non-surgical participants reporting excellent or good outcomes, seven more participants per 1000 (95% CI 199 fewer to 237 more) reported excellent or good satisfaction. Four studies (256 participants) assessed recurrent patellar subluxation at two to nine year follow-up. Based on an assumed risk of patellar subluxation in 292 out of 1000 in the non-surgical group, 73 fewer people per 1000 (95% CI 146 fewer to 35 more) had patellar subluxation as a result of surgery. Slightly more people had subsequent surgery in the non-surgical group. Pooled two to nine year follow-up data from three trials (195 participants) indicated that, based on an assumed risk of subsequent surgery in 215 people per 1000 in the non-surgical group, 118 fewer people per 1000 (95% CI 200 fewer to 372 more) had subsequent surgery after primary surgery. AUTHORS' CONCLUSIONS: We are uncertain whether surgery improves outcome compared to non-surgical management as the certainty of the evidence was very low. No sufficiently powered trial has examined people with recurrent patellar dislocation. Adequately powered, multicentre, randomised trials are needed. To inform the design and conduct of these trials, expert consensus should be achieved on the minimal description of both surgical and non-surgical interventions, and the pathological variations that may be relevant to both choice of these interventions.

Influence of platelet-rich plasma (PRP) analogues on healing and clinical outcomes following anterior cruciate ligament (ACL) reconstructive surgery: a systematic review.

PURPOSE: To systematically review the effect of PRP on healing (vascularization, inflammation and ligamentization) and clinical outcomes (pain, knee function and stability) in patients undergoing ACL reconstruction and compare the preparation and application of PRP. METHODS: Independent systematic searches of online databases (Medline, Embase and Web of Science) were conducted following PRISMA guidelines (final search 10th July 2021). Studies were screened against inclusion criteria and risk of bias assessed using Critical appraisal skills programme (CASP) Randomised controlled trial (RCT) checklist. Independent data extraction preceded narrative analysis. RESULTS: 13 RCTs were included. The methods of PRP collection and application were varied. Significant early increases in rate of ligamentization and vascularisation were observed alongside early decreases in inflammation. No significant results were achieved in the later stages of the healing process. Significantly improved pain and knee function was found but no consensus reached. CONCLUSIONS: PRP influences healing through early vascularisation, culminating in higher rates of ligamentization. Long-term effects were not demonstrated suggesting the influence of PRP is limited. No consensus was reached on the impact of PRP on pain, knee stability and resultant knee function, providing avenues for further research. Subsequent investigations could incorporate multiple doses over time, more frequent observation and comparisons of different forms of PRP. The lack of standardisation of PRP collection and application techniques makes comparison difficult. Due to considerable heterogeneity, (I2 > 50%), a formal meta-analysis was not possible highlighting the need for further high quality RCTs to assess the effectiveness of PRP. The biasing towards young males highlights the need for a more diverse range of participants to make the study more applicable to the general population. TRAIL REGISTRATION: CRD42021242078CRD, 15th March 2021, retrospectively registered.

A radiological index that influences the outcome following patellofemoral joint arthroplasty: the anterior trochlea offset ratio.

PURPOSE: Although largely successful, patellofemoral joint arthroplasty (PFA) has a less than satisfactory outcome in some patients. It was hypothesized that certain factors can be identified on radiological review that correlate with poor patient reported outcomes following PFA. METHODS: A retrospective cohort review of 369 patients undergoing PFA at our institution between 2005 and 2018 identified 43 "poor outcome" patients with an Oxford Knee Score (OKS) of less than 20 at 2 years follow up. These cases were matched by sex and age with 43 "good outcome" patients who had an OKS above 40 at 2 years post-op. Multiple radiological measurements were performed including anterior trochlea offset ratio (ATOR), component flexion/extension, component varus/valgus, component to bone width ratio and retinacular index. The OKS PROM was the primary outcome of the study. Stepwise logistic regression was performed to analyze the differences in radiological indices between the two groups. RESULTS: Intraclass correlation coefficients for inter-observer and intra-observer reliability were 0.90-0.98 for all indices measured. The only index demonstrating statistical significance between the groups was the ATOR (p = 0.003). The good outcome group had a mean ATOR of 0.19 whereas the poor outcome group had a mean ATOR of 0.24. CONCLUSIONS: Lower ATOR on radiological review was strongly associated with improved outcomes following PFA. The surgeon should therefore take particular care to prevent increasing the anterior offset of the trochlea component when performing PFA. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Group sequential designs in pragmatic trials: feasibility and assessment of utility using data from a number of recent surgical RCTs.

BACKGROUND: Assessing the long term effects of many surgical interventions tested in pragmatic RCTs may require extended periods of participant follow-up to assess effectiveness and use patient-reported outcomes that require large sample sizes. Consequently the RCTs are often perceived as being expensive and time-consuming, particularly if the results show the test intervention is not effective. Adaptive, and particularly group sequential, designs have great potential to improve the efficiency and cost of testing new and existing surgical interventions. As a means to assess the potential utility of group sequential designs, we re-analyse data from a number of recent high-profile RCTs and assess whether using such a design would have caused the trial to stop early. METHODS: Many pragmatic RCTs monitor participants at a number of occasions (e.g. at 6, 12 and 24 months after surgery) during follow-up as a means to assess recovery and also to keep participants engaged with the trial process. Conventionally one of the outcomes is selected as the primary (final) outcome, for clinical reasons, with others designated as either early or late outcomes. In such settings, novel group sequential designs that use data from not only the final outcome but also from early outcomes at interim analyses can be used to inform stopping decisions. We describe data from seven recent surgical RCTs (WAT, DRAFFT, WOLLF, FASHION, CSAW, FIXDT, TOPKAT), and outline possible group sequential designs that could plausibly have been proposed at the design stage. We then simulate how these group sequential designs could have proceeded, by using the observed data and dates to replicate how information could have accumulated and decisions been made for each RCT. RESULTS: The results of the simulated group sequential designs showed that for two of the RCTs it was highly likely that they would have stopped for futility at interim analyses, potentially saving considerable time (15 and 23 months) and costs and avoiding patients being exposed to interventions that were either ineffective or no better than standard care. We discuss the characteristics of RCTs that are important in order to use the methodology we describe, particularly the value of early outcomes and the window of opportunity when early stopping decisions can be made and how it is related to the length of recruitment period and follow-up. CONCLUSIONS: The results for five of the RCTs tested showed that group sequential designs using early outcome data would have been feasible and likely to provide designs that were at least as efficient, and possibly more efficient, than the original fixed sample size designs. In general, the amount of information provided by the early outcomes was surprisingly large, due to the strength of correlations with the primary outcome. This suggests that the methods described here are likely to provide benefits more generally across the range of surgical trials and more widely in other application areas where trial designs, outcomes and follow-up patterns are structured and behave similarly.

Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma.

Oncogenic KRAS mutations are absent in approximately 10% of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) and may represent a subgroup of mPDAC with therapeutic options beyond standard-of-care cytotoxic chemotherapy. While distinct gene fusions have been implicated in KRAS wildtype mPDAC, information regarding other types of mutations remain limited, and gene expression patterns associated with KRAS wildtype mPDAC have not been reported. Here, we leverage sequencing data from the PanGen trial to perform comprehensive characterization of the molecular landscape of KRAS wildtype mPDAC and reveal increased frequency of chr1q amplification encompassing transcription factors PROX1 and NR5A2. By leveraging data from colorectal adenocarcinoma and cholangiocarcinoma samples, we highlight similarities between cholangiocarcinoma and KRAS wildtype mPDAC involving both mutation and expression-based signatures and validate these findings using an independent dataset. These data further establish KRAS wildtype mPDAC as a unique molecular entity, with therapeutic opportunities extending beyond gene fusion events.

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.

Clinical and cost-effectiveness of Knee Arthroplasty versus Joint Distraction for Osteoarthritis (KARDS): protocol for a multicentre, phase III, randomised control trial.

INTRODUCTION: Knee replacement (KR) is a clinically proven procedure typically offered to patients with severe knee osteoarthritis (OA) to relieve pain and improve quality of life. However, artificial joints fail over time, requiring revision associated with higher mortality and inferior outcomes. With more young people presenting with knee OA and increasing life expectancy, there is an unmet need to postpone time to first KR. Knee joint distraction (KJD), the practice of using external fixators to open up knee joint space, is proposed as potentially effective to preserve the joint following initial studies in the Netherlands, however, has not been researched within an NHS setting. The KARDS trial will investigate whether KJD is non-inferior to KR in terms of patient-reported postoperative pain 12 months post-surgery. METHODS AND ANALYSIS: KARDS is a phase III, multicentre, pragmatic, open-label, individually randomised controlled non-inferiority trial comparing KJD with KR in patients with severe knee OA, employing a hybrid-expertise design, with internal pilot phase and process evaluation. 344 participants will be randomised (1:1) to KJD or KR. The primary outcome measure is the Knee Injury and Osteoarthritis Outcomes Score (KOOS) pain domain score at 12 months post-operation. Secondary outcome measures include patient-reported overall KOOS, Pain Visual Analogue Scale and Oxford Knee Scores, knee function assessments, joint space width, complications and further interventions over 24 months post-operation. Per patient cost difference between KR and KJD and cost per quality-adjusted life year (QALY) gained over 24 months will be estimated within trial, and incremental cost per QALY gained over 20 years by KJD relative to KR predicted using decision analytic modelling. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Research Ethics Committee (REC) and Health Research Authority (HRA). Trial results will be disseminated at clinical conferences, through relevant patient groups and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN14879004; recruitment opened April 2021.

Patient-reported outcome and survival following meniscal allograft transplantation : an international case series.

AIMS: Meniscal allograft transplantation (MAT) for patients with symptomatic meniscal loss has demonstrated good clinical results and survivorship. Factors that affect both functional outcome and survivorship have been reported in the literature. These are typically single-centre case series with relatively small numbers and conflicting results. Our aim was to describe an international, two-centre case series, and identify factors that affect both functional outcome and survival. METHODS: We report factors that affect outcome on 526 patients undergoing MAT across two sites (one in the UK and one in Italy). Outcomes of interest were the Knee injury and Osteoarthritis Outcome Score four (KOOS4) at two years and failure rates. We performed multiple regression analysis to examine for factors affecting KOOS, and Cox proportional hazards models for survivorship. RESULTS: Our results indicate that baseline KOOS4 score affects functional outcome at two years, but no other included factors were significantly related to functional outcome. The only factor that affected failure rate was the presence of cartilage lesions down to bone on both the femur and tibia, decreasing the five-year survivorship from 95% (95% confidence interval (CI) 91 to 99) to 84% (95% CI 74 to 94). CONCLUSION: To our knowledge, this is the largest international cohort reporting on MAT. Our results indicate that factors such as age, BMI, and cartilage lesions down to bone on both the femur and tibia of the affected compartment should not present barriers to offering MAT. Baseline KOOS4 score and the presence of bone-on-bone arthritis can be used to help counsel patients regarding the expected risks and rewards of surgery. Cite this article: Bone Joint J 2022;104-B(6):657-662.

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.

Tibial tuberosity-trochlear groove distance: does it measure up?

Recognized anatomic variations that lead to patella instability include patella alta and trochlea dysplasia. Lateralization of the extensor mechanism relative to the trochlea is often considered to be a contributing factor; however, controversy remains as to the degree this contributes to instability and how this should be measured. As the tibial tuberosity-trochlear groove (TT-TG) is one of most common imaging measurements to assess lateralization of the extensor mechanism, it is important to understand its strengths and weaknesses. Care needs to be taken while interpreting the TT-TG value as it is affected by many factors. Medializing tibial tubercle osteotomy is sometimes used to correct the TT-TG, but may not truly address the underlying anatomical problem. This review set out to determine whether the TT-TG distance sufficiently summarizes the pathoanatomy, and if this assists with planning of surgery in patellar instability. Cite this article: Bone Jt Open 2022;3(3):268-274.