Clinical assessment and management of lumbar spinal stenosis: clinical dilemmas and considerations for surgical referral.

Lumbar spinal stenosis is the leading indication for spine surgery in older adults. Surgery is recommended in clinical guidelines if non-surgical treatments have been provided with insufficient benefit. The difficulty for clinicians is that the current number of randomised controlled trials is low, which creates uncertainty about which treatments to provide. For non-surgical clinicians this paucity of data leads to a clinical dilemma of whether to continue managing the patient or refer to a spine surgeon. This Viewpoint aims to provide an update on the assessment of lumbar spinal stenosis, treatment recommendations, indications for referral to a spine surgeon, and current clinical dilemmas facing non-surgical clinicians and spinal surgeons.

The IDEAL framework for surgical robotics: development, comparative evaluation and long-term monitoring.

The next generation of surgical robotics is poised to disrupt healthcare systems worldwide, requiring new frameworks for evaluation. However, evaluation during a surgical robot's development is challenging due to their complex evolving nature, potential for wider system disruption and integration with complementary technologies like artificial intelligence. Comparative clinical studies require attention to intervention context, learning curves and standardized outcomes. Long-term monitoring needs to transition toward collaborative, transparent and inclusive consortiums for real-world data collection. Here, the Idea, Development, Exploration, Assessment and Long-term monitoring (IDEAL) Robotics Colloquium proposes recommendations for evaluation during development, comparative study and clinical monitoring of surgical robots-providing practical recommendations for developers, clinicians, patients and healthcare systems. Multiple perspectives are considered, including economics, surgical training, human factors, ethics, patient perspectives and sustainability. Further work is needed on standardized metrics, health economic assessment models and global applicability of recommendations.

How do pilot and feasibility studies inform randomised placebo-controlled trials in surgery? A systematic review.

INTRODUCTION: Randomised controlled trials (RCTs) with a placebo comparator are considered the gold standard study design when evaluating healthcare interventions. These are challenging to design and deliver in surgery. Guidance recommends pilot and feasibility work to optimise main trial design and conduct; however, the extent to which this occurs in surgery is unknown. METHOD: A systematic review identified randomised placebo-controlled surgical trials. Articles published from database inception to 31 December 2020 were retrieved from Ovid-MEDLINE, Ovid-EMBASE and CENTRAL electronic databases, hand-searching and expert knowledge. Pilot/feasibility work conducted prior to the RCTs was then identified from examining citations and reference lists. Where studies explicitly stated their intent to inform the design and/or conduct of the future main placebo-controlled surgical trial, they were included. Publication type, clinical area, treatment intervention, number of centres, sample size, comparators, aims and text about the invasive placebo intervention were extracted. RESULTS: From 131 placebo surgical RCTs included in the systematic review, 47 potentially eligible pilot/feasibility studies were identified. Of these, four were included as true pilot/feasibility work. Three were original articles, one a conference abstract; three were conducted in orthopaedic surgery and one in oral and maxillofacial surgery. All four included pilot RCTs, with an invasive surgical placebo intervention, randomising 9-49 participants in 1 or 2 centres. They explored the acceptability of recruitment and the invasive placebo intervention to patients and trial personnel, and whether blinding was possible. One study examined the characteristics of the proposed invasive placebo intervention using in-depth interviews. CONCLUSION: Published studies reporting feasibility/pilot work undertaken to inform main placebo surgical trials are scarce. In view of the difficulties of undertaking placebo surgical trials, it is recommended that pilot/feasibility studies are conducted, and more are reported to share key findings and optimise the design of main RCTs. PROSPERO REGISTRATION NUMBER: CRD42021287371.

Epidemiology of revision hip replacement surgery in the UK over the past 15 years-an analysis from the National Joint Registry.

OBJECTIVES: To investigate trends in the incidence rate and main indication for revision hip replacement (rHR) over the past 15 years in the UK. DESIGN: Repeated national cross-sectional study from 2006 to 2020. SETTING/PARTICIPANTS: rHR procedures were identified from the National Joint Registry for England, Wales, Northern Ireland, the Isle of Man and the States of Guernsey. Population statistics were obtained from the Office for National Statistics. MAIN OUTCOME MEASURES: Crude incidence rates of rHR. RESULTS: The incidence rate of rHR doubled from 11 per 100 000 adults in 2006 (95% CI 10.7 to 11.3) to a peak of 22 per 100 000 adults (95% CI 22 to 23) in 2012, before falling to 17 per 100 000 adults in 2019 (95% CI 16 to 17) (24.5% decrease from peak). The incidence rate of rHR reduced by 39% in 2020 compared with 2019 (during the COVID-19 pandemic). The most frequent indications for rHR between 2006 and 2019 were loosening/lysis (27.8%), unexplained pain (15.1%) and dislocation/instability (14.7%). There were incremental increases in the annual number and incidence rates of rHR for fracture, infection, dislocation/instability and a decrease in rHR for aseptic loosening/lysis. CONCLUSIONS: The incidence rate of rHR doubled from 2006 to 2012, likely due to high early failure rates of metal-on-metal hip replacements. The incidence of rHR then decreased by approximately 25% from 2012 to 2019, followed by a large decrease during the COVID-19 pandemic. The decrease in the number of rHR performed for aseptic loosening/lysis may reflect improved wear and implant longevity. Increased healthcare resource will be required to care for the increasing numbers of patients undergoing rHR for fracture and infection.

Remote Symptom Monitoring With Ecological Momentary Computerized Adaptive Testing: Pilot Cohort Study of a Platform for Frequent, Low-Burden, and Personalized Patient-Reported Outcome Measures.

BACKGROUND: Remote patient-reported outcome measure (PROM) data capture can provide useful insights into research and clinical practice and deeper insights can be gained by administering assessments more frequently, for example, in ecological momentary assessment. However, frequent data collection can be limited by the burden of multiple, lengthy questionnaires. This burden can be reduced with computerized adaptive testing (CAT) algorithms that select only the most relevant items from a PROM for an individual respondent. In this paper, we propose "ecological momentary computerized adaptive testing" (EMCAT): the use of CAT algorithms to reduce PROM response burden and facilitate high-frequency data capture via a smartphone app. We develop and pilot a smartphone app for performing EMCAT using a popular hand surgery PROM. OBJECTIVE: The aim of this study is to determine the feasibility of EMCAT as a system for remote PROM administration. METHODS: We built the EMCAT web app using Concerto, an open-source CAT platform maintained by the Psychometrics Centre, University of Cambridge, and hosted it on an Amazon Web Service cloud server. The platform is compatible with any questionnaire that has been parameterized with item response theory or Rasch measurement theory. For this study, the PROM we chose was the patient evaluation measure, which is commonly used in hand surgery. CAT algorithms were built using item response theory models derived from UK Hand Registry data. In the pilot study, we enrolled 40 patients with hand trauma or thumb-base arthritis, across 2 sites, between July 13, 2022, and September 14, 2022. We monitored their symptoms with the patient evaluation measure, via EMCAT, over a 12-week period. Patients were assessed thrice weekly, once daily, or thrice daily. We additionally administered full-length PROM assessments at 0, 6, and 12 weeks, and the User Engagement Scale at 12 weeks. RESULTS: The use of EMCAT significantly reduced the length of the PROM (median 2 vs 11 items) and the time taken to complete it (median 8.8 seconds vs 1 minute 14 seconds). Very similar scores were obtained when EMCAT was administered concurrently with the full-length PROM, with a mean error of <0.01 on a logit (z score) scale. The median response rate in the daily assessment group was 93%. The median perceived usability score of the User Engagement Scale was 4.0 (maximum possible score 5.0). CONCLUSIONS: EMCAT reduces the burden of PROM assessments, enabling acceptable high-frequency, remote PROM data capture. This has potential applications in both research and clinical practice. In research, EMCAT could be used to study temporal variations in symptom severity, for example, recovery trajectories after surgery. In clinical practice, EMCAT could be used to monitor patients remotely, prompting early intervention if a patient's symptom trajectory causes clinical concern. TRIAL REGISTRATION: ISRCTN 19841416; https://www.isrctn.com/ISRCTN19841416.

Patient-relevant outcomes following elective, aseptic revision knee arthroplasty: a systematic review.

BACKGROUND: The aim of this systematic review was to summarise the evidence for the clinical effectiveness of revision knee arthroplasty (rKA) compared to non-operative treatment for the management of patients with elective, aseptic causes for a failed knee arthroplasty. METHODS: MEDLINE, Embase, AMED and PsychINFO were searched from inception to 1st December 2020 for studies on patients considering elective, aseptic rKA. Patient-relevant outcomes (PROs) were defined as implant survivorship, joint function, quality of life (QoL), complications and hospital admission impact. RESULTS: No studies compared elective, aseptic rKA to non-operative management. Forty uncontrolled studies reported on PROs following elective, aseptic rKA (434434 rKA). Pooled estimates for implant survivorship were: 95.5% (95% CI 93.2-97.7%) at 1 year [seven studies (5524 rKA)], 90.8% (95% CI 87.6-94.0%) at 5 years [13 studies (5754 rKA)], 87.4% (95% CI 81.7-93.1%) at 10 years [nine studies (2188 rKA)], and 83.2% (95% CI 76.7-89.7%) at 15 years [two studies (452 rKA)]. Twelve studies (2382 rKA) reported joint function and/or QoL: all found large improvements from baseline to follow-up. Mortality rates were low (0.16% to 2% within 1 year) [four studies (353064 rKA)]. Post-operative complications were common (9.1 to 37.2% at 90 days). CONCLUSION: Higher-quality evidence is needed to support patients with decision-making in elective, aseptic rKA. This should include studies comparing operative and non-operative management. Implant survivorship following elective, aseptic rKA was ~ 96% at 1 year, ~ 91% at 5 years and ~ 87% at 10 years. Early complications were common after elective, aseptic rKA and the rates summarised here can be shared with patients during informed consent. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196922.

Patient-Relevant Outcomes Following First Revision Total Knee Arthroplasty, by Diagnosis: An Analysis of Implant Survivorship, Mortality, Serious Medical Complications, and Patient-Reported Outcome Measures Utilizing the National Joint Registry Data Set.

BACKGROUND: The purpose of this study was to investigate patient-relevant outcomes following first revision total knee arthroplasties (rTKAs) performed for different indications. METHODS: This population-based cohort study utilized data from the United Kingdom National Joint Registry, Hospital Episode Statistics Admitted Patient Care, National Health Service Patient-Reported Outcome Measures, and the Civil Registrations of Death. Patients undergoing a first rTKA between January 1, 2009, and June 30, 2019, were included in our data set. Patient-relevant outcomes included implant survivorship (up to 11 years postoperatively), mortality and serious medical complications (up to 90 days postoperatively), and patient-reported outcome measures (at 6 months postoperatively). RESULTS: A total of 24,540 first rTKAs were analyzed. The patient population was 54% female and 62% White, with a mean age at the first rTKA of 69 years. At 2 years postoperatively, the cumulative incidence of re-revision surgery ranged from 2.7% (95% confidence interval [CI], 1.9% to 3.4%) following rTKA for progressive arthritis to 16.3% (95% CI, 15.2% to 17.4%) following rTKA for infection. The mortality rate at 90 days was highest following rTKA for fracture (3.6% [95% CI, 2.5% to 5.1%]) and for infection (1.8% [95% CI, 1.5% to 2.2%]) but was <0.5% for other indications. The rate of serious medical complications requiring hospital admission within 90 days was highest for patients treated for fracture (21.8% [95% CI, 17.9% to 26.3%]) or infection (12.5% [95% CI, 11.2% to 13.9%]) and was lowest for those treated for progressive arthritis (4.3% [95% CI, 3.3% to 5.5%]). Patients who underwent rTKA for stiffness or unexplained pain had some of the poorest postoperative joint function (mean Oxford Knee Score, 24 and 25 points, respectively) and had the lowest proportion of responders (48% and 55%, respectively). CONCLUSIONS: This study found large differences in patient-relevant outcomes among different indications for first rTKA. The rate of complications was highest following rTKA for fracture or infection. Although rTKA resulted in large improvements in joint function for most patients, those who underwent surgery for stiffness and unexplained pain had worse outcomes. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Cost-effectiveness of replacing versus discarding the nail in children with nail bed injury.

Every year in the UK, around 10 000 children need to have operations to mend injuries to the bed of their fingernails. Currently, most children have their fingernail placed back on the injured nail bed after the operation. The NINJA trial found that children were slightly less likely to have an infection if the nail was thrown away rather than being put back, but the difference between groups was small and could have be due to chance. This study looked at whether replacing the nail is cost-effective compared with throwing it away. Using data from the NINJA trial, we compared costs, healthcare use, and quality of life and assessed the cost-effectiveness of replacing the nail. It was found that throwing the nail away after surgery would save the National Health Service (NHS) £75 (€85) per operation compared with placing the nail back on the nail bed. Changing clinical practice could save the NHS in England £720 000 (€819 000) per year.

Effectiveness of nail bed repair in children with or without replacing the fingernail: NINJA multicentre randomized clinical trial.

BACKGROUND: Surgery for nail bed injuries in children is common. One of the key surgical decisions is whether to replace the nail plate following nail bed repair. The aim of this RCT was to assess the clinical effectiveness and cost-effectiveness of nail bed repair with fingernail replacement/substitution compared with repair without fingernail replacement. METHODS: A two-arm 1 : 1 parallel-group open multicentre superiority RCT was performed across 20 secondary-care hospitals in the UK. The co-primary outcomes were surgical-site infection at around 7 days after surgery and cosmetic appearance summary score at a minimum of 4 months. RESULTS: Some 451 children presenting with a suspected nail bed injury were recruited between July 2018 and July 2019; 224 were allocated to the nail-discarded arm, and 227 to the nail-replaced arm. There was no difference in the number of surgical-site infections at around 7 days between the two interventions or in cosmetic appearance. The mean total healthcare cost over the 4 months after surgery was €84 (95 per cent c.i. 34 to 140) lower for the nail-discarded arm than the nail-replaced arm (P < 0.001). CONCLUSION: After nail bed repair, discarding the fingernail was associated with similar rates of infection and cosmesis ratings as replacement of the finger nail, but was cost saving. Registration number: ISRCTN44551796 (http://www.controlled-trials.com).

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.

Serious adverse event rates and reoperation after arthroscopic shoulder surgery: population based cohort study.

OBJECTIVE: To provide clinicians and patients with accurate risk estimates of serious adverse events after common elective shoulder arthroscopic procedures, including reoperation within one year. DESIGN: Population based cohort study. SETTING: Hospital Episode Statistics for NHS England, including civil registration mortality data from the Office for National Statistics. PARTICIPANTS: 288 250 arthroscopic shoulder procedures performed in 261 248 patients aged ≥16 years between 1 April 2009 and 31 March 2017. Elective procedures were grouped into subacromial decompression, rotator cuff repair, acromioclavicular joint excision, glenohumeral stabilisation, and frozen shoulder release. MAIN OUTCOME MEASURES: The primary outcomes were rates of serious adverse events (mortality, pulmonary embolism, pneumonia, myocardial infarction, acute kidney injury, stroke, and urinary tract infection) requiring inpatient care within 90 days post-surgery. Secondary outcomes were specific adverse event rates at 90 days, and reoperations (including for deep infection) within one year. RESULTS: The overall rate of complications within 90 days after arthroscopic shoulder surgery (including reoperation) was low at 1.2% (95% confidence interval 1.2% to 1.3%), with one in 81 patients at risk, and varied according to type of procedure, from 0.6% (0.5% to 0.8%) for glenohumeral stabilisation to 1.7% (1.5% to 1.8%) for frozen shoulder release. After adjustment for age, comorbidities, and sex, no effect of procedure type was observed. Pneumonia was the most common adverse event (0.3%, 0.3% to 0.4%), with one in 303 patients at risk. Pulmonary embolic events were rare, at 0.1% (0.1% to 0.1%), with one in 1428 patients at risk. At one year, the overall rate for reoperation was 3.8% (3.8% to 3.9%), with one in 26 patients at risk, ranging from 2.7% (2.5% to 3.0%) for glenohumeral stabilisation to 5.7% (5.4% to 6.1%) for frozen shoulder release. The overall rate of further surgery for deep infection was low, at 0.1% (0.1% to 0.1%), with one in 1111 patients at risk, but was higher after rotator cuff repair (0.2%, 0.2% to 0.2%), with one in 526 patients at risk. Over the study period the number of arthroscopic shoulder procedures increased, except for subacromial decompression, which decreased. CONCLUSIONS: The findings of this study suggest that risks of serious adverse events associated with common shoulder arthroscopy procedures are low. Nevertheless, serious complications do occur, and include the risk of reoperation in one in 26 patients within one year. STUDY REGISTRATION: Clinical. TRIALS: gov NCT03573765.

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability. METHODS: We did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score-4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367. FINDINGS: Between Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5-13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications. INTERPRETATION: Surgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management. FUNDING: The UK National Institute for Health Research Health Technology Assessment Programme.

ACL Surgery Necessity in Non-Acute Patients (ACL SNNAP): a statistical analysis plan for a randomised controlled trial.

BACKGROUND: Rupture of the anterior cruciate ligament (ACL) is a common injury, primarily affecting young, active individuals. Despite surgical intervention being the more common treatment for patients suffering ACL ruptures, current management is based on limited and generally low-quality evidence. We describe a statistical analysis plan (SAP) for the ACL SNNAP randomised controlled trial, which aims to investigate the necessity of surgical management in patients with ACL injuries. METHODS/DESIGN: ACL SNNAP is a pragmatic, multi-centre, superiority, parallel-group randomised controlled trial in participants with a symptomatic non-acute ACL deficient knee. Participants are allocated in a 1:1 ratio to either non-surgical management (rehabilitation) or surgical management (reconstruction) with the aim of assessing the efficacy and cost-effectiveness. The primary outcome of the study is the Knee Injury and Osteoarthritis Outcome Score (KOOS4) at 18 months post-randomisation. The KOOS4 score at 18 months will be evaluated using a linear regression model adjusting for recruitment centre and baseline KOOS4 scores, allowing for intra-centre correlation. A secondary analysis of the primary outcome will be carried out using an area under the curve (AUC) approach using treatment estimates obtained from a mixed model using baseline, 6 months, 12 months, and 18 months post-randomisation outcome data. Secondary outcomes will be measured at 18 months and will include return to activity/level of sport participation, intervention-related complications, the EQ-5D-5L questionnaire, all 5 individual subscales of the KOOS questionnaire, the ACL-QOL score, expectations of return to activity and cost-effectiveness of the interventions. Missing primary outcome data will be investigated through a sensitivity analysis. Full details of the planned methods for the statistical analysis of clinical outcomes are presented in this paper. The study protocol for the ACL SNNAP trial has been published previously. DISCUSSION: The methods of analysis for the ACL SNNAP trial have been described here to minimise the risk of data-driven results and reporting bias. Any deviations from the analysis methods described in this paper will be described in full and justified in the publications of the trial results. TRIAL REGISTRATION: ISRCTN ISRCTN10110685 . Registered on 16 November 2016.

Early patient-reported outcomes from primary hip and knee arthroplasty have improved over the past seven years : an analysis of the NHS PROMs dataset.

AIMS: Routinely collected patient-reported outcome measures (PROMs) have been useful to quantify and quality-assess provision of total hip arthroplasty (THA) and total knee arthroplasty (TKA) in the UK for the past decade. This study aimed to explore whether the outcome following primary THA and TKA had improved over the past seven years. METHODS: Secondary data analysis of 277,430 primary THAs and 308,007 primary TKAs from the NHS PROMs programme was undertaken. Outcome measures were: postoperative Oxford Hip/Knee Score (OHS/OKS); proportion of patients achieving a clinically important improvement in joint function (responders); quality of life; patient satisfaction; perceived success; and complication rates. Outcome measures were compared based on year of surgery using multiple linear and logistic regression models. RESULTS: For primary THA, multiple linear regression modelling found that more recent year of surgery was associated with higher postoperative OHS (unstandardized coefficient (B) 0.15 points (95% confidence interval (CI) 0.14 to 0.17); p < 0.001) and higher EuroQol five-dimension index (EQ-5D) utility (B 0.002 (95% CI 0.001 to 0.002); p < 0.001). The odds of being a responder (odds ratio (OR) 1.02 (95% CI 1.02 to 1.03); p < 0.001) and patient satisfaction (OR 1.02 (95% CI 1.01 to 1.03); p < 0.001) increased with year of surgery, while the odds of any complication reduced (OR 0.97 (95% CI 0.97 to 0.98); p < 0.001). No trend was found for perceived success (p = 0.555). For primary TKA, multiple linear regression modelling found that more recent year of surgery was associated with higher postoperative OKS (B 0.21 points (95% CI 0.19 to 0.22); p < 0.001) and higher EQ-5D utility (B 0.002 (95% CI 0.002 to 0.003); p < 0.001). The odds of being a responder (OR 1.04 (95% CI 1.03 to 1.04); p < 0.001), perceived success (OR 1.02 (95% CI 1.01 to 1.02); p < 0.001), and patient satisfaction (OR 1.02 (95% CI 1.01 to 1.02); p < 0.001) all increased with year of surgery, while the odds of any complication reduced (OR 0.97 (95% CI 0.97 to 0.97); p < 0.001). CONCLUSION: Nearly all patient-reported outcomes following primary THA/TKA improved by a small amount over the past seven years. Due to the high proportion of patients achieving good outcomes, PROMs following THA and TKA may need to focus on better discrimination of patients achieving high scores to be able to continue to measure improvement in outcomes. Cite this article: Bone Joint J 2022;104-B(6):687-695.

Evaluation of placebo fidelity and trial design methodology in placebo-controlled surgical trials of musculoskeletal conditions: a systematic review.

ABSTRACT: The number of placebo surgical trials on musculoskeletal conditions is increasing, but little is known about the quality of their design and methods. This review aimed to (1) assess the level of placebo fidelity (ie, degree to which the placebo control mimicked the index procedure) in placebo trials of musculoskeletal surgery, (2) describe the trials' methodological features using the adapted Applying Surgical Placebo in Randomised Evaluations (ASPIRE) checklist, and (3) describe each trial's characteristics. We searched 4 electronic databases from inception until February 18, 2021, for randomised trials of surgery that included a placebo control for any musculoskeletal condition. Protocols and full text were used to assess placebo fidelity (categorised as minimal, low, or high fidelity). The adapted 26-item ASPIRE checklist was also completed on each trial. PROSPERO registration number: CRD42021202131. A total of 30,697 studies were identified in the search, and 22 placebo-controlled surgical trials of 2045 patients included. Thirteen trials (59%) included a high-fidelity placebo control, 7 (32%) used low fidelity, and 2 (9%) minimal fidelity. According to the ASPIRE checklist, included trials had good reporting of the "rationale and ethics" (68% overall) and "design" sections (42%), but few provided enough information on the "conduct" (13%) and "interpretation and translation" (11%) of the placebo trials. Most trials sufficiently reported their rationale and ethics, but interpretation and translation are areas for improvement, including greater stakeholder involvement. Most trials used a high-fidelity placebo procedure suggesting an emphasis on blinding and controlling for nonspecific effects.

Unicompartmental compared with total knee replacement for patients with multimorbidities: a cohort study using propensity score stratification and inverse probability weighting.

BACKGROUND: Although routine NHS data potentially include all patients, confounding limits their use for causal inference. Methods to minimise confounding in observational studies of implantable devices are required to enable the evaluation of patients with severe systemic morbidity who are excluded from many randomised controlled trials. OBJECTIVES: Stage 1 - replicate the Total or Partial Knee Arthroplasty Trial (TOPKAT), a surgical randomised controlled trial comparing unicompartmental knee replacement with total knee replacement using propensity score and instrumental variable methods. Stage 2 - compare the risk benefits and cost-effectiveness of unicompartmental knee replacement with total knee replacement surgery in patients with severe systemic morbidity who would have been ineligible for TOPKAT using the validated methods from stage 1. DESIGN: This was a cohort study. SETTING: Data were obtained from the National Joint Registry database and linked to hospital inpatient (Hospital Episode Statistics) and patient-reported outcome data. PARTICIPANTS: Stage 1 - people undergoing unicompartmental knee replacement surgery or total knee replacement surgery who met the TOPKAT eligibility criteria. Stage 2 - participants with an American Society of Anesthesiologists grade of ≥ 3. INTERVENTION: The patients were exposed to either unicompartmental knee replacement surgery or total knee replacement surgery. MAIN OUTCOME MEASURES: The primary outcome measure was the postoperative Oxford Knee Score. The secondary outcome measures were 90-day postoperative complications (venous thromboembolism, myocardial infarction and prosthetic joint infection) and 5-year revision risk and mortality. The main outcome measures for the health economic analysis were health-related quality of life (EuroQol-5 Dimensions) and NHS hospital costs. RESULTS: In stage 1, propensity score stratification and inverse probability weighting replicated the results of TOPKAT. Propensity score adjustment, propensity score matching and instrumental variables did not. Stage 2 included 2256 unicompartmental knee replacement patients and 57,682 total knee replacement patients who had severe comorbidities, of whom 145 and 23,344 had linked Oxford Knee Scores, respectively. A statistically significant but clinically irrelevant difference favouring unicompartmental knee replacement was observed, with a mean postoperative Oxford Knee Score difference of < 2 points using propensity score stratification; no significant difference was observed using inverse probability weighting. Unicompartmental knee replacement more than halved the risk of venous thromboembolism [relative risk 0.33 (95% confidence interval 0.15 to 0.74) using propensity score stratification; relative risk 0.39 (95% confidence interval 0.16 to 0.96) using inverse probability weighting]. Unicompartmental knee replacement was not associated with myocardial infarction or prosthetic joint infection using either method. In the long term, unicompartmental knee replacement had double the revision risk of total knee replacement [hazard ratio 2.70 (95% confidence interval 2.15 to 3.38) using propensity score stratification; hazard ratio 2.60 (95% confidence interval 1.94 to 3.47) using inverse probability weighting], but half of the mortality [hazard ratio 0.52 (95% confidence interval 0.36 to 0.74) using propensity score stratification; insignificant effect using inverse probability weighting]. Unicompartmental knee replacement had lower costs and higher quality-adjusted life-year gains than total knee replacement for stage 2 participants. LIMITATIONS: Although some propensity score methods successfully replicated TOPKAT, unresolved confounding may have affected stage 2. Missing Oxford Knee Scores may have led to information bias. CONCLUSIONS: Propensity score stratification and inverse probability weighting successfully replicated TOPKAT, implying that some (but not all) propensity score methods can be used to evaluate surgical innovations and implantable medical devices using routine NHS data. Unicompartmental knee replacement was safer and more cost-effective than total knee replacement for patients with severe comorbidity and should be considered the first option for suitable patients. FUTURE WORK: Further research is required to understand the performance of propensity score methods for evaluating surgical innovations and implantable devices. TRIAL REGISTRATION: This trial is registered as EUPAS17435. 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. 25, No. 66. See the NIHR Journals Library website for further project information.

We compared the risks and benefits of partial and total knee replacements in NHS patients with a complex medical history who would normally be excluded from randomised trials on this topic. We used information that was collected during hospital appointments for people who had a knee replacement between 2009 and 2016. It is difficult to directly compare the two groups because each individual patient has a different medical history. We tested advanced statistical methods to account for these differences. In stage 1, we showed that some of these advanced statistical methods could replicate the results of a recently published surgical trial using routine data from the NHS. We compared patients in the trial with similar patients who were operated on in the NHS. Three of the proposed methods showed results similar to those obtained from the Total or Partial Knee Arthroplasty Trial (TOPKAT). In stage 2, we used the successful methods from stage 1 to study the risks, benefits and costs of partial and total knee replacement surgery in patients with complex medical histories. Two of the statistical methods found that patients who had a partial knee replacement had less self-reported pain and better function after surgery than patients who had a total knee replacement. All three methods found that partial knee replacement was safer, was associated with a lower risk of blood clots (a known complication of knee surgery) and had lower mortality over 5 years. However, patients who had a partial knee replacement were twice as likely as those with a total knee replacement to need a second surgery within 5 years. We found that partial knee replacements were less costly to the NHS and were associated with better overall quality of life for patients than total knee replacement.

Placebo comparator group selection and use in surgical trials: the ASPIRE project including expert workshop.

BACKGROUND: The use of placebo comparisons for randomised trials assessing the efficacy of surgical interventions is increasingly being considered. However, a placebo control is a complex type of comparison group in the surgical setting and, although powerful, presents many challenges. OBJECTIVES: To provide a summary of knowledge on placebo controls in surgical trials and to summarise any recommendations for designers, evaluators and funders of placebo-controlled surgical trials. DESIGN: To carry out a state-of-the-art workshop and produce a corresponding report involving key stakeholders throughout. SETTING: A workshop to discuss and summarise the existing knowledge and to develop the new guidelines. RESULTS: To assess what a placebo control entails and to assess the understanding of this tool in the context of surgery is considered, along with when placebo controls in surgery are acceptable (and when they are desirable). We have considered ethics arguments and regulatory requirements, how a placebo control should be designed, how to identify and mitigate risk for participants in these trials, and how such trials should be carried out and interpreted. The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Surgical placebos might be most appropriate when there is poor evidence for the efficacy of the procedure and a justified concern that results of a trial would be associated with a high risk of bias, particularly because of the placebo effect. CONCLUSIONS: The use of placebo controls is justified in randomised controlled trials of surgical interventions provided that there is a strong scientific and ethics rationale. Feasibility work is recommended to optimise the design and implementation of randomised controlled trials. An outline for best practice was produced in the form of the Applying Surgical Placebo in Randomised Evaluations (ASPIRE) guidelines for those considering the use of a placebo control in a surgical randomised controlled trial. LIMITATIONS: Although the workshop participants involved international members, the majority of participants were from the UK. Therefore, although every attempt was made to make the recommendations applicable to all health systems, the guidelines may, unconsciously, be particularly applicable to clinical practice in the UK NHS. FUTURE WORK: Future work should evaluate the use of the ASPIRE guidelines in making decisions about the use of a placebo-controlled surgical trial. In addition, further work is required on the appropriate nomenclature to adopt in this space. FUNDING: Funded by the Medical Research Council UK and the National Institute for Health Research as part of the Medical Research Council-National Institute for Health Research Methodology Research programme.

WHAT WAS THE RESEARCH ABOUT?: One of the best ways to prove that a new medicine really works is to use a scientific test called a 'placebo-controlled trial'. In this type of test, half of the participants are given a new pill and the other half are given a 'placebo', which is a dummy pill (usually a sugar pill) that is made to taste and look the same as the active pill, but has no active ingredients. The results are then compared. Just like medicines, new surgical procedures need to be tested to show that they are safe and benefit patients. Ideally, they would also be tested using the 'placebo-controlled trial' approach, but asking patients to have 'dummy' surgery is not the same as asking people to take a dummy pill. Placebo surgery raises lots of ethics questions and is controversial. As it is controversial, guidelines are needed to recommend when placebo surgery studies can be used (if at all) and what special considerations need to be taken into account. Our research team was commissioned to develop these guidelines. WHAT DID WE DO?: We summarised, to the best of our knowledge, all previous research that had used placebo surgery and reviewed all the ethics literature on this topic. We also looked at the latest scientific understanding of how placebos work. We then held a workshop to discuss and summarise the existing knowledge and to develop the new guidelines. This involved an international team of patients, surgeons, researchers, ethicists, psychologists, physiologists and funders. We published the guidelines [i.e. the ASPIRE (Applying Surgical Placebo in Randomised Evaluations) guidelines] in an influential medical journal and also wrote several other publications. This report provides a slightly more detailed version of our findings and recommendations. WHO WILL THIS HELP?: The guidelines will help researchers and doctors know when, and how, to best design placebo surgery studies in the future.

Phase 3 Trials of Enhanced Versus Usual Care Physical Therapy for Patients at Risk of Poor Outcome Following Knee Arthroplasty: A Perspective on Meaning and a Way Forward.

Physical therapy is routinely delivered to patients after discharge from the hospital following knee arthroplasty. Posthospitalization physical therapy is thought to be beneficial, particularly for those patients most at risk of poor outcome, the subgroup with persistent function-limiting pain, despite an apparently successful surgery. Research teams have undertaken 3 large-scale multicenter Phase 3 randomized clinical trials designed specifically for patients at risk of poor outcome following knee arthroplasty. All 3 trials screened for poor outcome risk using different methods and investigated different physical therapist interventions delivered in different ways. Despite the variety of types of physical therapy and mode of delivery, all trials found no effects of the enhanced treatment compared with usual care. In all cases, usual care required a lower dosage of physical therapy compared with the enhanced interventions. This Perspective compares and contrasts the 3 trials, speculates on factors that could explain the no-effect findings, and proposes areas for future study designed to benefit the poor outcome phenotype.

Patient-Reported Function and Quality of Life After Revision Total Knee Arthroplasty: An Analysis of 10,727 Patients from the NHS PROMs Program.

BACKGROUND: The aim of the study was to investigate changes in patient-reported outcome measures (PROMs) after revision total knee arthroplasty (rTKA). METHODS: A total of 10,727 patients undergoing elective rTKA were recruited from the UK National Health Service PROMs data set from 2013 to 2019. PROMs were collected at baseline and six months to assess joint function (Oxford Knee Score, OKS) and quality of life (EQ-5D). Associations with a change in the OKS (COKS) were investigated through multiple linear regression. RESULTS: The mean COKS was 12.4 (standard deviation 10.7) points. A total of 6776 of 10,329 (65.6%) patients demonstrated increase in the OKS above the minimal important change of 7.5 points. The median change in the EQ-5D utility was 0.227 (interquartile range 0.000 to 0.554). A total of 4917 of 9279 (53.0%) patients achieved a composite endpoint of improvement greater than the minimal important change for joint function and 'better' QoL as per the Paretian analysis. A total of 7477 of 10,727 (69.7%) patients reported satisfaction with rTKA. A total of 7947 of 10,727 (74.1%) patients felt surgery was a success. A total of 4888 of 10,632 (46.0%) patients reported one or more adverse events. A higher preoperative OKS was associated with a lower COKS (coefficient -0.63 [95% confidence interval -0.67 to -0.60]). Other factors associated with a lower COKS were postoperative complication(s), age under 60 years, longer duration of knee problems, patients who identified as disabled, problems in EQ-5D dimensions of anxiety/depression and self-care, comorbid conditions (circulatory problems, diabetes, and depression), and earlier year of procedure in the data set. CONCLUSION: Two-thirds of patients experienced a meaningful improvement in joint function after rTKA. However, there was a high frequency of patient-reported complications. These findings may enable better informed discussion of the risks and benefits of discretionary rTKA.