Hip bearing surfaces materials are typically broadly reported in national registry (metal-on-polyethylene, ceramic-on-ceramic etc). We investigated the revision rates of primary total hip replacement (THR) reported in the National Joint Registry (NJR) by detailed types of bearing surfaces used.

We analysed THR procedures across all orthopaedic units in England and Wales. Our analyses estimated all-cause and cause-specific revision rates. We identified primary THRs with heads and monobloc cups or modular acetabular component THRs with detailed head and shell/liner bearing material combinations. We used flexible parametric survival models to estimate adjusted hazard ratios (HR).

A total of 1,026,481 primary THRs performed between 2003–2019 were included in the primary analysis (Monobloc cups: n=378,979 and Modular cups: n=647,502) with 20,869 (2%) of these primary THRs subsequently undergoing a revision episode (Monobloc: n=7,381 and Modular: n=13,488).

Compared to implants with a cobalt chrome head and highly crosslinked polyethylene (HCLPE) cup, the overall risk of revision for monobloc acetabular implant was higher for patients with cobalt chrome or stainless steel head and non-HCLPE cup. The risk of revision was lower for patients with a delta ceramic head and HCLPE cup implant, at any post-operative period.

Compared to patients with a cobalt chrome head and HCLPE liner primary THR, the overall risk of revision for modular acetabular implant varied non-constantly. THRs with a delta ceramic or oxidised zirconium head and HCLPE liner had a lower risk of revision throughout the entire post-operative period.

The overall and indication-specific risk of prosthesis revision, at different time points following the initial implantation, is reduced for implants with a delta ceramic or oxidised zirconium head and a HCLPE liner/cup in reference to THRs with a cobalt chrome head and HCLPE liner/cup.

Hip prosthetic joint infection (PJI) is a debilitating complication following joint replacement surgery, with significant impact on patients and healthcare systems. The INFection ORthopaedic Management: Evidence into Practice (INFORM:EP) study, builds upon the 6-year INFORM programme by developing evidence-based guidelines for the identification and management of hip PJI.

A panel of 21 expert stakeholders collaborated to develop best practice guidelines based on evidence from INFORM \[1\]. An expert consensus process was used to refine guidelines using RAND/UCLA criteria. The guidelines were then implemented over a 12-month period through a Learning Collaborative of 24 healthcare professionals from 12 orthopaedic centres in England. Qualitative interviews were conducted with 17 members of the collaborative and findings used to inform the development of an implementation support toolkit. Patient and public involvement contextualised the implementation of the guidelines. The study is registered with the ISCRTN (34710385).

The INFORM guidelines, structured around the stages of PJI management, were largely supported by surgeons, although barriers included limited awareness among non-surgical team members, lack of job planning for multidisciplinary teams, and challenges in ensuring timely referrals from primary care. Psychological support for patients was identified as a critical gap. Advanced Nurse Practitioners and multidisciplinary team (MDT) coordinators were seen as potential bridges to address these knowledge gaps. The guidelines were also viewed as a useful tool for service development.

This study presents the first evidence-based guidelines for hip PJI management, offering a comprehensive approach to prevention, treatment, and postoperative care. Effective implementation is crucial, involving wider dissemination amongst primary and community care, as well as non-specialist treatment centres. Further resources are needed to ensure job planning for MDTs and psychological support for patients. Overall, this study lays the foundation for improved PJI management, benefiting patients and healthcare systems.

Implants in total hip replacement (THR) are associated with different clinical and cost-effectiveness profiles,. We estimate the costs and outcomes for NHS patients in the year after THR associated with implant bearing materials using linked routinely collected data.

We linked NJR primary elective THR patients for osteoarthritis to HES and National PROMs. We estimated health care costs, health-related quality of life indices, and revision risks, in the year after primary and revision THRs overall. We used generalised linear models adjusting for patient and hospital characteristics and estimated 10-year cumulative probability of revision. We imputed utilities using chained equations for half the sample with missing PROMS.

We linked 577,973 elective primary THRs and 11,812 subsequent revisions. One year after primary THR, patients with the cemented THRs using cobalt chrome or stainless steel head with HCLPE liner/cup cost the NHS, on average, £13,101 (95%CI £13,080,£13,122), had an average quality-of-life score of 0.788 (95%CI 0.787,0.788), and a 10-year revision probability of 1.9% (95%CI 1.6,2.3). Compared to the reference, patients receiving a cemented THR with delta ceramic head and HCLPE liner/cup, hybrid THR with delta ceramic head and HCLPE liner/cup, and hybrid THR with alumina head and HCLPE liner/cup had lower 1-year costs (-£572 \[95% CI -£775,-£385\], -£346 \[-£501,-£192\], -£371 \[-£574,-£168\] respectively), better quality of life (0.007 \[95% CI 0.003,0.011\], 0.013 \[0.010,0.016\], 0.009 \[0.005,0.013\] respectively), and lower 10-year revision probabilities (1.4% \[1.03,2.0\], 1.5 \[1.3,1.7\], 1.6%\[1.2,2.1\] respectively).

Implant bearing materials are associated with varying mean costs and health outcomes after primary THR. Ours is the first study to derive costs and health outcomes from large, linked databases using multiple imputation methods to deal with bias. Our findings are useful for commissioning and procurement decisions and to inform a subsequent cost-effectiveness model with more granular detail on THR implant types.

Abstract

There is paucity of reliable data examining the treatment pathway for hip replacements over the life of the patient in terms of risk of revision and re-revisions.

We did a retrospective observational registry-based study of the National Joint Registry, using data on hip replacements from all participating hospitals in England and Wales, UK. We included data on all first revisions, with an identifiable primary procedure, with osteoarthritis as the sole indication for the original primary procedure. Kaplan-Meier estimates were used to determine the cumulative probability of revision and subsequent re-revision after primary hip replacement. Analyses were stratified by age and gender, and the influence of time from first to second revision on the risk of further revision was explored.

Between 2003, and 2019, there were 29 010 revision hip replacements with a linked primary episode. Revision rates of revision hip replacements were higher in patients younger than 55 years than in older age groups. After revision of primary total hip replacement, 21·3% (95% CI 18·6–24·4) of first revisions were revised again within 15 years, 22·3% (20·3–24·4) of second revisions were revised again within 7 years, and 22·3% (18·3–27·0) of third revisions were revised again within 3 years. After revision of hip resurfacing, 23·7% (95% CI 19·6–28·5) of these revisions were revised again within 15 years, 21·0% (17·0–25·8) of second revisions were revised again within 7 years, and 19·3% (11·9–30·4) of third revisions were revised again within 3 years. A shorter time between revision episodes was associated with earlier subsequent revision.

Younger patients are at an increased risk of multiple revisions. Patients who undergo a revision have a steadily increasing risk of further revision the more procedures they undergo, and each subsequent revision lasts for approximately half the time of the previous one.

Introduction and Objective

An important subset of patients is dissatisfied after total joint arthroplasty (TJA) due to residual functional impairment. This study investigated the assessment of objectively measured step-up performance following TJA, to identify patients with poor functional improvement after surgery, and to predict residual functional impairment during early postoperative rehabilitation. Secondary, longitudinal changes of block step-up (BS) transfers were compared with functional changes of subjective patient reported outcome measures (PROMs) following TJA.

A recent French report suggested that cobalt metal ions released from total hip replacements (THRs) were associated with an increased risk of dilated cardiomyopathy and heart failure. If the association is causal the consequences would be significant given the millions of Orthopaedic procedures in which cobalt-chrome is used annually. We examined whether cobalt-chrome containing THRs were associated with an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders.

Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 375,067 primary THRs with up to 14·5 years follow-up. Implants were grouped as either containing cobalt-chrome or not containing cobalt-chrome. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined.

There were 132,119 individuals (35·2%) with an implant containing cobalt-chrome. There were 48,106 deaths, 27,406 heart outcomes, 35,823 cancers, and 22,097 neurodegenerative disorders. There was no evidence of an association that patients with cobalt-chrome implants had higher rates of any of the outcomes. For all-cause mortality there was a very small survival advantage for patients having a cobalt-chrome implant (restricted mean survival time 13·8=days, 95% CI=6·8-20·9).

Cobalt-chrome containing THRs did not have an increased risk of all-cause mortality, heart failure, cancer, and neurodegenerative disorders into the second decade post-implantation. Our findings will reassure clinicians and patients that primary THR is not associated with systemic implant effects.

Total hip replacement (THR) for end-stage osteoarthritis is a commonly performed cost-effective procedure, which provides patients with significant clinical improvement. Estimating the future demand for joint replacement is important to identify the healthcare resources needed. We estimated the number of primary THRs that will need to be performed up to the year 2060.

We used data from The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man on the current volume of primary THR (n=94,936) performed in 2018. We projected future numbers of THR using a static estimated rate from 2018 applied to population growth forecast data from the UK Office for National Statistics up to 2060.

By 2060, primary THR volume would increase from 2018 levels by an estimated 37.7% (n=130,766). For both males and females demand for surgery was also higher for patients aged 70 and over, with older patients having the biggest relative increase in volume over time: 70–79 years (144.6% males, 141.2% females); 80–89 years (212.4% males, 185.6% females); 90 years and older (448.0% males, 298.2% females).

By 2060 demand for THR is estimated to increase by almost 40%. Demand will be greatest in older patients (70 years+), which will have significant implications for the health service that requires forward planning given morbidity and resource use is higher in this population. There is a backlog of current demand with cancellation of elective surgery due to seasonal flu pressures in 2017 and now Covid-19 in 2020. Orthopaedics already has the largest waiting list of any speciality. These issues will negatively impact the health services ability to deliver timely joint replacement to many patients for a number of years and require urgent planning.

Total hip replacements (THRs) are performed by surgeons at various stages in their training, with varying levels of senior supervision. There is a balance between protecting training opportunities for the next generation of surgeons, while limiting the exposure of patients to unnecessary risk during the training process. The aim of this study was to examine the association between surgeon grade, the senior supervision of trainees, and the risk of revision following THR.

We included 603 474 primary THRs recorded in the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man (NJR) between 2003 and 2016 for an indication of osteoarthritis. Exposures were the grade of the surgeon (consultant or trainee), and whether trainees were supervised by a scrubbed consultant or not. Outcomes were all-cause revision, the indication for revision, and the temporal variation in risk of revision (all up to 10 years). Net failure was calculated using Kaplan-Meier analysis and adjusted analyses used Cox regression and flexible parametric survival analysis (adjusted for patient, operative, and unit level factors).

There was no association between surgeon grade and all-cause revision up to 10 years (crude hazard ratio (HR) 0·999, 95% confidence interval (CI) 0.936–1.065; p=0.966); a finding which persisted with adjusted analysis. Adjusted analysis demonstrated an association between trainees operating without supervision by a scrubbed consultant and an increase in all-cause revision (HR 1.100, 95% CI 1.002–1.207; p=0.045). There was an association between the trainee-performed THRs and revision due to instability (crude HR 1.143, 95% CI, 1.007–1.298; p=0.039). However, this was not observed in fully adjusted models, or when trainees were supervised by a scrubbed consultant.

Within the current training system in the United Kingdom, trainees achieve comparable outcomes to consultant surgeons when supervised by a scrubbed consultant. Revision rates are higher when trainees are not supervised by a scrubbed consultant but remain within internationally recognised acceptable limits.

Considerable debate exists regarding which agent(s) should be preferred for venous thromboembolism (VTE) chemical prophylaxis following joint replacement. We assessed the practice of surgeons regarding VTE chemical prophylaxis for primary THR and TKR, pre and post issuing of updated NICE guidance in 2018.

A survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients were assessed post publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored. Questions were also asked about surgeon equipoise for participation in future RCTs.

Following the new guidance, 34% (n=87) used low-molecular weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH), and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone, and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs. after=73%;p<0.001), and aspirin for TKR (before=18% vs. after=84%;p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs. after=92.6%;p=0.011) and TKR (before=87.0% vs. after=98.8%;p<0.001). Support from surgeons for future RCTs was dependent on the clinical question, ranging from 48% participation in trials (effectiveness of aspirin vs. a DOAC) to 79% (effectiveness of 14 days LMWH vs. 28 days LMWH).

Over one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis. Furthermore, there is an appetite amongst UK surgeons for participating in future RCTs, with a trial comparing standard versus extended duration LMWH likely feasible in current practice.

Aims

To develop and externally validate a parsimonious statistical prediction model of 90-day mortality after elective total hip arthroplasty (THA), and to provide a web calculator for clinical usage.

Total hip replacements (THRs) provide pain relief and improved function to thousands of patients suffering from end-stage osteoarthritis, every year. Over 800 different THR constructs were implanted in the UK in 2017. To ensure reliable implants are used, a NICE revision benchmark of 5% after 10 years exists. Given the 10-year cumulative mortality of patients under 55 years of age receiving THRs is only 5% and that a recent study suggests 25-year THR survival of 58%, we aim to produce revision estimates out to 30 years that may guide future long-term benchmarks.

The local database of the Princess Elizabeth Orthopaedic Centre (PEOC), Exeter, holds data on over 20,000 patients with nearly 30-years follow-up with contemporary prostheses. A previous study suggests that the results of this centre are generalisable if comparisons restricted to the same prostheses. Via flexible parametric survival analysis, we created an algorithm using this database, for revision of any part of the construct for any reason, controlling for age and gender. This algorithm was applied to 664,761 patients in the NJR who have undergone THR, producing a revision prediction for patients with the same prostheses as those used at this centre.

Using our algorithm, the 10-year predicted revision rate of THRs in the NJR was 2.2% (95% CI 1.8, 2.7) based on a 68-year-old female patient; well below the current NICE benchmark. Our predictions were validated by comparison to the maximum observed survival in the NJR (14.2 years) using restricted mean survival time (P=0.32). Our predicted cumulative revision estimate after 30 years is 6.5% (95% CI 4.5, 9.4). The low observed and predicted revision rate with the prosthesis combinations studied, suggest current benchmarks may be lowered and new ones introduced at 15 and 20 years to encourage the use of prostheses with high survival.

Over 800 total hip replacement (THR) constructs were implanted in the UK in 2017. To ensure reliable implants are used, a NICE revision benchmark of 5% after 10 years exists. Surgeons are guided in choice by organisations such as the Orthopaedic Data Evaluation Panel (ODEP). Currently, ODEP publishes ratings for stem and cup separately and not for constructs. We used NJR data to investigate whether revision estimates of an individual stem (with all cups) is an accurate indicator of survival of all constructs using that stem.

The dataset comprised 234,289 THRs using the most frequently implanted stem between 2004 and 2017. Crude ten-year revision estimates were calculated using Kaplan-Meier for all THRs and for the five most implanted constructs. Adjusted comparisons between individual constructs and the overall stem revision estimate were made using flexible parametric survival analysis.

The 10-year crude, revision estimate for all THRs was 2.3% (95% CI 2.2, 2.4). Only four of the most frequently used constructs had long enough follow-up to analyse. 10-year estimates for these constructs ranged from 1.8% (95% CI 1.5, 2.1) to 3.7% (95% CI 3.2, 4.1), a log-rank test revealed strong evidence against the null hypothesis that revision estimates were the same for all constructs (p<0.001). Adjusted for age, sex and ASA, three of the four constructs showed a difference in 10-year revision estimates compared to this stem with all cups (P=0.03, P<0.001, P<0.001).

This study suggests 10-year revision estimates for all THRs using the most implanted stem in the NJR are not representative of all constructs involving that stem in crude or adjusted analyses. Current benchmarking systems report survival for the stem in combination with all cups and not for constructs. We suggest that benchmarking ratings basing on revision estimates for THR constructs would provide more accurate information, enabling informed construct decisions.

Aims

The aim of this study was to conduct evidence synthesis on the available published literature of the impact of the training status of the operating surgeon (trainee vs. consultant) on the survival and revision rate of primary hip and knee replacements.

Aims

To calculate how the likelihood of obtaining measurable benefit from hip or knee arthroplasty varies with preoperative patient-reported scores.

Background

Total hip replacement (THR) is clinically and cost-effective. The surgical approach influences outcomes, however there is little generalisable and robust evidence to guide practice. We assessed the effect of surgical approach on THR outcomes.

Introduction

Analysis of registry data shows that few units achieve results better than 99·98% control limits. Implant selection is considered a predictor of outcome variation in joint replacement. We analysed the outcomes of a unit with statistically “better than expected” results and compared to all other units within the National Joint Registry for England, Wales, Northern Ireland and Isle of Man (NJR). We sought to determine whether improved implant survival following primary total hip replacement (THR) is a centre effect or mediated by implant selection.

Introduction

Total hip arthroplasty (THA) is indicated in independently mobile patients sustaining displaced intracapsular hip fractures. Studies presently suggest that the anterolateral approach is preferable to the posterior approach due to a perceived reduced risk of reoperations and dislocations. However, these observations come from small studies with short follow-up. We assessed whether surgical approach in THA performed for hip fractures effects outcomes.

The aim of this study was to determine the outcomes and survivorship of the Triathlon knee replacement at 7 years after surgery. A cohort of 266 patients receiving a Triathlon knee replacement were assessed before surgery and at 3 months, 1 year, 2 years, 3 years, 5 years and 7 years post-operation. Patient-reported outcomes were assessed using the WOMAC, KOOS Knee-Related Quality of Life scale, Satisfaction Scale and questions on kneeling ability and whether they regretted having the operation. Data on survivorship was collected from self-report and medical records. At 7 years after surgery, 32 patients were deceased, and 17 patients were withdrawn. Of the 217 patients remaining in the study, 164 (76%) returned a completed study questionnaire. At 7 years after surgery, 92% of patients reported an improvement in their WOMAC Pain score greater than the minimally clinically important improvement (defined as improvement of ≥9 points from before surgery) and 82% reported this in their WOMAC Function score (defined as improvement of ≥12 points). Knee-related quality of life was good, with a mean score of 66.8 (SD 26.0) (0–100 scale, worst to best). A high percentage of patients (89%) were somewhat or very satisfied with their outcome at 7 years. Survivorship with revision as the endpoint was 96.4% (95% CI 93.2–98.1%) at 7 years post-operation. Five percent of patients regretted having their operation and 68% reported much difficulty or an inability to kneel. In conclusion, this study observed good long-term patient outcomes and survivorship of the Triathlon knee replacement.

Periprosthetic joint infections (PJIs) are uncommon but are devastating complications of total knee replacement (TKR). We analysed the risk factors of revision for PJI following primary TKR and their association with PJI at different post-operative periods. Primary TKRs and subsequent revision surgeries performed for PJI from 2003–2014 were identified from the National Joint Registry (NJR). Multilevel piece-wise exponential non-proportional hazards models were used to estimate the effect of the investigated factors at different post-operative periods. Patient, perioperative and healthcare system characteristics were investigated and data from the Hospital Episode Statistics for England were linked to obtain information on specific comorbidities. The index TKRs consisted of 679,010 primaries with 3,659 subsequently revised for PJI, 7% within 3 months, 6% between 3–6months, 17% between 6–12months, 27% between 1–2years and 43% ≥2 years from the index procedure. Risk factors for revision for PJI included male sex, high BMI, high ASA grade and young age. Patients with chronic pulmonary disease, diabetes and liver disease had higher risk of revision for PJI, as had patients who had a primary TKR for an indication of trauma or inflammatory arthropathy. Surgical procedure, fixation method, constraint and bearing type influenced the risk of revision for PJI. Their effects were period-specific. No or small associations were found with the operating surgeon grade, surgical volume and hospital surgical volume. These findings from the world's largest joint replacement registry show a more complex picture than the meta-analyses published to date with specific time-dependent effects for the identified risk factors.

Administration of perioperative antibiotic prophylaxis (AP) reduces the risk of prosthetic joint infection (PJI) following primary total hip (THA) and knee (TKA) arthroplasty. The optimal type of antibiotic used, and duration of prophylaxis are subject to debate. We compared the risk of revision surgery for PJI in the first year following THA and TKA by AP regimen. A national survey collecting information on hospital-level AP regimen policy was conducted across the Netherlands and linked to data from the LROI arthroplasty registry for 2011–2015. PJI status was defined using the surgical indication reported at revision by surgeons in the registry form. Restricted cubic splines Poisson model adjusted for hospital clustering were used to conduct the comparisons on 130,712 THAs and 111,467 TKAs performed across 99 institutions. These included 399 THAs and 303 TKAs revised for an indication of PJI. Multiple shot of Cefazolin (MCZ), of cefuroxime (MCX) and single shot of Cefazolin (SCZ) were respectively administrated to 87%, 4% and 9% of patients. For THA, the rates of revision for PJI were respectively 31/10,000 person-years 95%CI[28, 35], 39[25, 59] and 23[15, 34] in the groups which received MCZ, MCX and SCZ; respectively, the rates for TKA were 27[24, 31], 40[24, 62] and 24[16, 36]. No evidence of difference between AP regimens was found in the unadjusted and adjusted model (age, gender, BMI and ASA grade). Further work is advocated to confirm whether there is an association between AP regimen collected at patient-level and the risk of subsequent revision for PJI.

Introduction

The development of an algorithm that provides accurate individualised estimates of revision risk could help patients make informed surgical treatment choices. This requires building a survival model based on fixed and modifiable risk factors that predict outcome at the individual level. Here we compare different survival models for predicting prosthesis survivorship after hip replacement for osteoarthritis using data from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR).

Osteoarthritis of the hip is common and the mainstay of surgical treatment for end-stage disease is total hip replacement. There are few RCTs comparing long-term outcomes between prostheses; therefore, surgeons and patients are reliant on single-centre case-series and recently, analysis of joint registries, when making evidence-based implant choices.

We conducted a systematic review, conforming to PRISMA, of Medline and Embase in September 2017. Single-centre case-series and papers analysing registries were included. Series looking at disease-specific cohorts (other than OA), under 15 years follow-up or lacking survival analyses were excluded. Resurfacings, revisions and complex-primaries were also excluded. 2750 abstracts were screened, resulting in 299 full-text articles. Following full review 124 articles were excluded and 21 series added from references, resulting in 150 analyses of individual prostheses/constructs and 12 papers from registries. We also analysed annual reports of registries.

Registry data indicated cemented prostheses tended to better outcomes at late follow-ups, whereas case-series showed cementless prostheses tended to have better survival past 15 years with revision for any reason (of stem, cup or either component) as the end-point.

The discrepancy between results from registry data and single-centre case series is stark, and whilst the reasons for these differences may be multifactorial, single-centre case-series included in this review often lacked sufficient power to provide precise estimates of survival. This is contrasted to data from registries, which tended to have far greater numbers from multiple centres, allowing results to be generalised to the population.

The difference between these two modes of analysis suggests bias exists in selection and outcomes from single-centre series. The varied quality of reporting in case-series make it difficult for a reader to adequately assess bias, and accurately inform contemporary decision making.

Surgeons and patients should be cautious when interpreting single-centre case series and systems relying on data generated from them.

Introduction

Prosthetic joint infection (PJI) is an uncommon but serious complication of hip replacement.

A recent systematic review of patient risk factors for PJI identified male gender, smoking status, increasing BMI, steroid use, previous joint surgery and comorbidities of diabetes, rheumatoid arthritis and depression as risk factors for developing PJI. Limitations of the current literature include the short term follow up of most published studies.

We investigated the role of patient, surgical and healthcare factors on the risk of revision of a primary hip replacement for PJI at different time-points in the post-operative follow-up. It is important that those risk factors are identified so that patients can be appropriately counselled according to their individual risk profile prior to surgery and modifiable factors can be addressed to reduce the risk of PJI at an individual and healthcare system level.

Background

To aid recovery, rehabilitation is an important adjunct to surgery. Acknowledging the MRC framework for complex interventions we assessed the evidence-base for components of comprehensive rehabilitation in total hip (THR) and total knee replacement (TKR) pathways.

Background

Inpatient physiotherapy is routinely provided after total knee replacement (TKR) surgery to enhance recovery prior to discharge. However, the provision of outpatient physiotherapy is variable in the UK, and the longer-term benefits of outpatient physiotherapy are unclear. This study aimed to evaluate the feasibility of conducting a randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of group-based outpatient physiotherapy after TKR.

Background

Total knee replacement (TKR) is an effective operation for many patients, however approximately 20% of patients experience chronic pain and functional limitations in the months and years following their TKR. If modifiable pre-operative risk factors could be identified, this would allow patients to be targeted with individualised care to optimise these factors prior to surgery and potentially improve outcomes. Psychosocial factors have also been found to be important in predicting outcomes in the first 12 months after TKR, however their impact on long-term outcomes is unknown. This study aimed to identify pre-operative psychosocial predictors of patient-reported and clinician-assessed outcomes at one year and five years after primary TKR.

With the increasing demand for hip and knee replacement and move towards seven-day services, we examined whether this planned, elective surgery performed at the weekend is associated with a different 30-day mortality versus that performed between Monday and Friday.

The study dataset comprised 118,096 joint replacement episodes performed at the weekend and 1,233,882 episodes done on a weekday. We used a Kaplan-Meier framework to examine the 30-day cumulative mortality rate for all elective hip and knee replacements performed in England and Wales and recorded in the NJR between 1st April 2003 and 31st December 2014, with Cox proportional-hazards regression models to assess for time-dependent variation and adjust for identified risk factors for mortality.

For hip replacement the cumulative 30-day mortality was 0.15% (95%CI: 0.12–0.19) for patients operated on at the weekend versus 0.20% (0.19–0.21) for patients undergoing surgery during the normal working week. For knee replacement the cumulative 30-day mortality was 0.14% (0.11–0.17) for patients operated on at the weekend versus 0.18% (0.17–0.19) for patients undergoing surgery during the normal working week. The lower mortality associated with weekend operating was most apparent in the later years of the audit (2009 to 2014) and remained after adjustment for any differences in patient age, gender, American Society of Anaesthesiologist grade, surgeon seniority, surgical and anaesthetic practices, and thrombo-prophylaxis choice in weekend versus weekday operated patients.

Routine hip and knee replacements performed at the weekend in England and Wales and are not associated with an increased risk of post-operative mortality.

Aims

To investigate whether elective joint arthroplasty performed at the weekend is associated with a different 30-day mortality versus that performed between Monday and Friday.

With the increasing demand for hip and knee replacement, and the increasing pressure to move towards routine seven-day services within the National Health Service, the trend towards weekend operating is set to increase. We aimed to determine whether planned, elective total hip and total knee replacement performed at the weekend is associated with a different 30-day mortality versus those performed between Monday and Friday.

We used National Joint Registry of England, Wales, Northern Ireland and Isle of Man (NJR) linked to Office for National Statistics (ONS) data. The study dataset comprised 118,096 joint replacement episodes performed at the weekend and 1,233,882 episodes done on a weekday. The main outcome measure was 30-day all-causes mortality. We applied a survivorship analysis using a Kaplan-Meier framework to examine the 30-day cumulative mortality rate for all elective hip and knee replacements performed in England and Wales between 1st April 2003 and 31st December 2014, with Cox proportional-hazards regression models to assess for time-dependent variation and adjust for identified risk factors for mortality.

For hip replacement the cumulative 30-day mortality was 0.15% (95%CI: 0.12–0.19) for patients operated on at the weekend versus 0.20% (0.19–0.21) for patients undergoing surgery during the normal working week. For knee replacement the cumulative 30-day mortality was 0.14% (0.11–0.17) for patients operated on at the weekend versus 0.18% (0.17–0.19) for patients undergoing surgery during the normal working week. The lower mortality associated with weekend operating was most apparent in the later years of the audit (2009 to 2014) and remained after adjustment for any differences in patient age, gender, American Society of Anaesthesiologist grade, surgeon seniority, surgical and anaesthetic practices, and thrombo-prophylaxis choice in weekend versus weekday operated patients.

Hip and knee replacements are routinely performed on Saturdays, and to a lesser extent on Sundays, in England and Wales and are not associated with an increased risk of post-operative mortality.

Background

Chronic pain after joint replacement is common, affecting approximately 10% of patients after total hip replacement (THR) and 20% of patients after total knee replacement (TKR). Heightened generalised sensitivity to nociceptive input could be a risk factor for the development of this pain. The primary aim of this study was to investigate whether preoperative widespread pain sensitivity was associated with chronic pain after joint replacement.

Background

There is a paucity of long term data concerning the pre and postoperative patient reported function of total knee replacement. The aim of this study was to determine the mortality, implant survivorship, patient reported function and satisfaction in a cohort of 114 patients, from a single centre, who received a Kinemax total knee replacement more than 15 years ago.

Background

To investigate whether the interaction between pre-operative widespread hyperalgesia and radiographic osteoarthritis (OA) was associated with pain severity before and after total hip replacement (THR) and total knee replacement (TKR).

Background

In the UK, over 160,000 total joint replacements are performed annually. About 1% of patients subsequently develop a deep bacterial infection and, if untreated, this can result in severe pain, disability, and death. Costs to the NHS are substantial. The INFORM (Infection Orthopaedic Management) programme aims to address gaps in knowledge relating to treatment of deep prosthetic joint infection through six work packages. The programme is supported by a patient forum and patient-partners working on oversight groups.

Background

Assessment of functional outcome after total hip arthroplasty (THA) often involves subjective patient-reported outcome measures (PROMs) whereas analysis of gait allows more objective assessment. The aims of the study were to compare longitudinal changes of WOMAC function score and ambulatory gait analysis after THA, between patients with low and high self-reported levels of physical function.

Background

Frequency of primary total hip (THA) and total knee (TKA) arthroplasty procedures is increasing, with a subsequent rise in revision procedures. This study aims to describe timing and excess surgical mortality associated with revision THA and TKA compared to those on the waiting list.

Background

Post-traumatic immunosuppression (PTI) after surgery increases vulnerability to nosocomial infections, sepsis, and death. Knee arthroplasty offers a sterile clinical model to characterise PTI and explore its underlying mechanisms.

Objective

There is limited information about the extent to which the association between pre-operative and chronic post-operative pain is mediated via pain-on-movement or pain-at-rest. We explored these associations in patients undergoing total hip (THR) and total knee (TKR) replacement.

Background

Over 96% of primary total hip replacements (THR) recorded in the National Joint Registry (NJR) are performed through a posterior or lateral surgical approach. There is no high quality evidence available to support the use of one approach over the other in primary THR and even less evidence when the outcome of revision THR is considered.

Background

Total hip replacement (THR) and total knee replacement (TKR) are usually effective at relieving pain; however, 7–23% of patients experience chronic post-surgical pain. These trials aimed to investigate the effect of local anaesthetic wound infiltration on pain severity at 12 months after primary THR or TKR for osteoarthritis.

Background

Dissociation of the polyethylene liner is a known failure mechanism of the Harris Galante I and II uncemented acetabular components. The outcomes of revision surgery for this indication and the influence of time to diagnosis are not well described.

Background

This article reviews four commonly used approaches to assess patient responsiveness to a treatment or therapy [Return To Normal (RTN), Minimal Important Difference (MID), Minimal Clinically Important Difference (MCID), OMERACT-OARSI (OO)], and demonstrates how each of the methods can be formulated in a multi-level modelling (MLM) framework.

Background

The two-stage revision strategy has been claimed as being the “gold standard” for treating prosthetic joint infection. The one-stage revision strategy remains an attractive alternative option, however, its effectiveness in comparison to the two-stage strategy remains uncertain. A systematic review and meta-analysis was conducted to compare the effectiveness of one- and two-stage revision strategies to prevent re-infection after prosthetic hip infection.

Physical functioning in patients undergoing hip surgery is commonly assessed in three ways: patient-reported outcome measure (PROM), performance test, or clinician-administered measure. It is recommended that several types of measures are used concurrently to capture an extended picture of function. Patient fatigue and burden, time, resources and logistical constraints of clinic and research appointments mean that collecting multiple measures is seldom feasible, leading to focus on a limited number of measures, if not a single one. While there is evidence that performance-tests and PROMs do not fully correlate, correlations between PROMs, performance tests and clinician-administrated measures are yet to be evaluated. It is also not known if the associations between function and patient characteristics depend on how function is measured. The aim of our study was to use different measures to assess function in the same group of patients before their hip surgery to determine 1. how well PROMs, performance tests and clinician-administrated measures correlate with one another and 2. Whether these measures are associated with the same patient characteristics.

We conducted a cross-sectional analysis of the pre-operative information of 125 participants listed for hip replacement. The WOMAC function subscale, Harris Hip Score (HHS) and walk-, step- and balance-tests were assessed by questionnaire or during a clinic visit. Participant socio-demographics and medical characteristics were also collected. Correlations between functional measures were investigated with correlation coefficients (r). Regression models were used to test the association between the patient's characteristics and each of the three types of functional measures.

None of the correlations between the PROM, clinician-administrated measure and performance tests were very high (r<0.90). The highest correlations were found between the WOMAC-function and the HHS (r=0.7) or the Walk-test (r=0.6), and between the HHS and the walk-test(r=0.7). All the other performance-tests had low correlations with the other measures(r ranging between 0.3 and 0.5).

The associations between patient characteristics and functional scores varied by type of measure. Psychological status was associated with the WOMAC function (p-value<0.0001) but not with the other measures. Age was associated with the performance test measures (p-value ranging from ≤0.01 to <0.0001) but not with the WOMAC function. The clinician-administered (HHS) measure was not associated with age or psychological status.

When evaluating function prior to hip replacement clinicians and researchers should be aware that each assessment tool captures different aspects of function and that patient characteristics should be taken into account. Psychological status influences the perception of function; patients may be able to do more than they think they can do, and may need encouragement to overcome anxiety. A performance test like a walk-test would provide a more comprehensive assessment of function limitations than a step or balance test, although performance tests are influenced by age.

For the most precise description of functional status a combination of measures should be used. Clinicians should supplement their pre-surgery assessment of function with patient-reported measure to include the patient's perspective.

Joint arthroplasty is a common surgical procedure, with over 185,000 primary hip and knee arthroplasties performed in England, Wales and Northern Ireland in 2014. After total hip or knee arthroplasty, about 1% of patients develop deep prosthetic joint infection (PJI), which usually requires further major operations to clear the infection. Although PJI affects only a small percentage of patients it is one of the most devastating complications associated with this procedure. Research evidence has focussed on clinical effectiveness of revision surgery while there has been less focus on the impact on patients and support needs. Using a systematic review approach, the aim of this study was to assess support needs and evaluate what interventions are routinely offered to support patients undergoing treatment for PJI following hip or knee arthroplasty.

We systematically searched MEDLINE, Embase, Web of Science, PsycINFO, Cinahl, Social Science Citation Index, and The Cochrane Library from 1980 to February 15, 2015 for observational (prospective cohort, nested case-control, case-control, and retrospective cohort) studies, qualitative studies, and clinical trials that report on the support needs and interventions for patients being treated for PJI or other major adverse occurrences following joint arthroplasty. Data were extracted by two independent investigators and consensus reached with involvement of a third.

Of 4,161 potentially relevant citations, we identified one case-control, one prospective cohort and two qualitative studies for inclusion in the synthesis. Patients report that PJI and treatment had a profoundly negative impact affecting physical, emotional, social and economic aspects of their lives. No study evaluated support interventions for PJI or other major adverse occurrences following hip and knee arthroplasty.

The interpretation of study results is limited by variation in study design, outcome measures and the small number of relevant eligible studies. Findings show that patients undergoing treatment for PJI have extensive physical, psychological, social and economic support needs. Our review highlights a lack of evidence about support strategies for patients undergoing treatment for PJI and other adverse occurrences. There is a need to design, implement and evaluate interventions to support these patients.

Around 20% of patients who have total knee replacement find that they experience long-term pain afterwards. There is a pressing need for better treatment and management for patients who have this kind of pain but there is little evidence about how to improve care. To address this gap we are developing a complex intervention comprising a clinic to assess potential causes of a patient's long-term pain after knee replacement and onwards referral to appropriate, existing services. The Medical Research Council recommends that development of complex interventions include several stages of development and refinement and involvement of stakeholders. This study comprises the penultimate stage in the comprehensive development of this intervention. Earlier stages included a survey of current practice, focus groups with healthcare professionals, a systematic review of the literature and expert deliberation.

Healthcare professionals from diverse clinical backgrounds with experience of caring for patients with long-term pain after knee replacement were sent a study information pack. Professionals who wished to participate were asked to return their signed consent form and completed study questionnaire to the research team. Participants rated the appropriateness of different aspects of the assessment process and care pathway from 1–9 (not appropriate to very appropriate). Data were collated and a document prepared, consisting of anonymised mean appropriateness ratings and summaries of free-text comments. This document was then discussed in 4 facilitated meetings with healthcare professional held at the future trial centres. A summary report and revised care pathway was then prepared and sent to participants for further comments.

28 professionals completed the questionnaire and/or attended a meeting. Participants included surgeons, physiotherapists, nurses, pain specialists and rheumatologists. Mean appropriateness scores ranged from 6.9 to 8.4. Taking a score of 7–9 as agreement, consensus was achieved that the assessment should be performed at 3 months post-operative by an extended scope practitioner/nurse, treatment be guided by a standardised assessment of pain, and treatment individualised. There was also agreement that referrals in the care pathway to surgical review, GP and pain clinics were appropriate. Nurse-led/self-monitoring was rated lower (6.9) because of considerations about the need to ensure that patients receive appropriate support, follow-up and referral to other services.

This work demonstrates the research methods that can be used to refine the design of a complex intervention. The process and findings enable refinement of an intervention for patients with long-term pain after knee replacement. The next stage of intervention development will assess the acceptability and reliability of the assessment process, and the usability of the intervention's standard operating procedures. The intervention will then be evaluated by a larger research team in a multi-centre randomised controlled trial, starting in late 2016.

Prosthetic joint infection (PJI) is an uncommon but serious complication of hip and knee replacement. We investigated the rates of revision surgery for the treatment of PJI following primary and revision hip and knee replacement, explored time trends, and estimated the overall surgical burden created by PJI.

We analysed the National Joint Registry for England and Wales for revision hip and knee replacements performed for a diagnosis of PJI and their index procedures from 2003–2014. The index hip replacements consisted of 623,253 primary and 63,222 aseptic revision hip replacements with 7,642 revisions subsequently performed for PJI; for knee replacements the figures were 679,010 primary and 33,920 aseptic revision knee replacements with 8,031 revisions subsequently performed for PJI. Cumulative incidence functions, prevalence rates and the burden of PJI in terms of total procedures performed as a result of PJI were calculated.

Revision rates for PJI equated to 43 out of every 10,000 primary hip replacements (2,705/623,253), i.e. 0.43%(95%CI 0.42–0.45), subsequently being revised due to PJI. Around 158 out of every 10,000 aseptic revision hip replacements performed were subsequently revised for PJI (997/63,222), i.e. 1.58%(1.48–1.67). For knees, the respective rates were 0.54%(0.52–0.56) for primary replacements, i.e. 54 out of every 10,000 primary replacements performed (3,659/679,010) and 2.11%(1.96–2.23) for aseptic revision replacements, i.e. 211 out of every 10,000 aseptic revision replacements performed (717/33,920). Between 2005 and 2013, the risk of revision for PJI in the 3 months following primary hip replacement rose by 2.29 fold (1.28–4.08) and after aseptic revision by 3.00 fold (1.06–8.51); for knees, it rose by 2.46 fold (1.15–5.25) after primary replacement and 7.47 fold (1.00–56.12) after aseptic revision. The rates of revision for PJI performed at any time beyond 3 months from the index surgery remained stable or decreased over time.

From a patient perspective, after accounting for the competing risk of revision for an aseptic indication and death, the 10-year cumulative incidence of revision hip replacement for PJI was 0.62%(95%CI 0.59–0.65) following primary and 2.25%(2.08–2.43) following aseptic revision; for knees, the figures were 0.75%(0.72–0.78) following primary replacement and 3.13%(2.81–3.49) following aseptic revision.

At a health service level, the absolute number of procedures performed as a consequence of hip PJI increased from 387 in 2005 to 1,013 in 2014, i.e. a relative increase of 2.6 fold. While 70% of those revisions were two-stage, the use of single stage revision increased from 17.6% in 2005 to 38.5% in 2014. For knees, the burden of PJI increased by 2.8 fold between 2005 and 2014. Overall, 74% of revisions were two-stage with an increase in use of single stage from 10.0% in 2005 to 29.0% in 2014.

Although the risk of revision due to PJI following hip or knee replacement is low, it is rising. Given the burden and costs associated with performing revision joint replacement for prosthetic joint infection and the predicted increased incidence of both primary and revision hip replacement, this has substantial implications for service delivery.

Patients report similar or better pain and function before revision hip arthroplasty than before primary arthroplasty but poorer outcomes after revision surgery. The trajectory of post-operative recovery during the first 12 months and any differences by type of surgery have received little attention. We explored the trajectories of change in pain and function after revision hip arthroplasty to 12-months post-operatively and compared them with those observed after primary hip arthroplasty.

We conducted a single-centre UK cohort study of patients undergoing primary (n = 80) or revision (n = 43) hip arthroplasty. WOMAC pain and function scores and 20-metres walking time were collected pre-operatively, at 3 and 12-months post-operatively. Multilevel regression models were used to chart and compare the trajectories of post-operative change (0–3 months and 3–12 months) between the types of surgery.

Patients undergoing primary arthroplasty had a total hip replacement (n=74) or hip resurfacing (n=6). Osteoarthritis was the indication for surgery in 92% of primary cases. Patients undergoing revision arthroplasty had revision of a total hip arthroplasty (n=37), hemiarthroplasty (n=2) or hip resurfacing (n=4). The most common indication for revision arthroplasty was aseptic loosening (n=29); the remaining indications were pain (n=4), aseptic lymphocyte-dominated vasculitis-associated lesion (n=4) or other reasons (n=6). Primary (87%) and revision arthroplasties (98%) were mostly commonly performed via a posterior surgical approach.

The improvements in pain and function following revision arthroplasty occurred within the first 3-months following operation (WOMAC-pain, p<0.0001; WOMAC-function, p<0.0001; timed 20-metres walk, p<0.0001) with no evidence of further change beyond this initial period (p>0.05)

While the pattern of recovery after revision arthroplasty was similar to that observed after primary arthroplasty, improvements in the first 3-months were smaller after revision compared to primary arthroplasty (p<0.0001). Patients listed for revision surgery reported lower pre-operative pain levels (p=0.03) but similar post-operative levels (p=0.268) compared to those undergoing primary surgery. At 12-months post-operation patients who underwent a revision arthroplasty had not reached the same level of function achieved by those who underwent primary arthroplasty (WOMAC-function p=0.015; Time walk p=0.004).

Patients undergoing revision hip arthroplasty should be informed that the majority of their improvement will occur in the first 3-months following surgery and that the expected improvement will be less marked than that experienced following primary surgery. More research is now required to 1.) identify whether specific in-patient and post-discharge rehabilitation tailored towards patients undergoing revision arthroplasty would improve or achieve equivalent outcomes to primary surgery and 2.) whether patients who are achieving limited improvements at 3-months post-operative would benefit from more intensive rehabilitation. This will become all the more important with the increasing volume of revision surgery and the high expectations of patients who aspire to a disease-free and active life.

Around 1% of the 185,000 primary hip and knee arthroplasties performed in the UK are followed by prosthetic joint infection (PJI). Although PJI affects a small percentage of patients, it is one of the most devastating complications associated with this procedure. Treatment usually involves further major surgery which can adversely affect patients' quality of life. Understanding current service provision provides valuable information needed to design and evaluate support interventions for patients. The aim of this survey was to identify usual care pathways and support in UK NHS orthopaedic centres for this population.

The 20 highestvolume UK NHS orthopaedic centresfor hip and knee arthroplasty account for 33–50% of all cases treated for prosthetic joint infection. Infection leads at each centre were invited to participate in a survey about usual care provision and support for PJI. Questions exploredfollow up time-points; use of standard outcome measures; multidisciplinary care plans; supportive in-patient care and care after treatment; and onward referrals. Survey responses were recorded on a standardised proforma. Data were entered into Excel for analysis, then reviewed and coded into categories and frequency statistics to describe categorical data. A descriptive summary was developed based on these categories.

Eleven of the highestvolume orthopaedic centres completed the survey. Follow-up of patients varied greatly across centres; some centres reviewed patients at weekly or 2 week intervals, while all centres saw patients at 6 weeks. Long-term follow-up varied across centres from 3–4 monthsto 12 monthly. Length of follow-up period varied from until the infection had cleared toindefinitely. Follow-up timepoints were only standardised in 4 out of 11 centres. Only 1 centre had a dedicated infection clinic. Advice on who patients should contact if they had concerns included the consultant, community nurse, extended scope practitioner or the ward, while 3 centres told patients to avoid calling their GP. Only half of the centres routinely used standardised outcome measures with patients with PJI. The majority of centres provided standard physiotherapy and occupational therapy (OT) to in-patients while approximately half also offered social support. Only one centre provided dedicated physiotherapy and OT on a separate infection ward. Three centres provided hospital at home or community services to patients in-between operative stages. Only 3 out of 11 centres stated they had specific multidisciplinary care plans in place for patients. Once discharged most patients were provided with physiotherapy, OT and social services if needed. Common barriersto referral included complexities of referring patients outside the hospital catchment area;lack of availability of community services, and shortage of staff including physiotherapists. Delays in rehab and social services could also be problematic.

Findings show wide variation intreatment pathways and support for patients treated for PJI, both as inpatients and in the community. Only one of the 11 centreswho participated had a dedicated infection clinic. Only one centre suggested they individualised their physiotherapy support. A number of barriers exist to referring patients on to other support services after revision surgery.

Total hip replacement (THR) is a common elective surgical procedure and can be effective for reducing chronic pain. However, waiting times for THR can be considerable, and patients often experience significant pain during this time. A pain self-management intervention may provide patients with the skills to enable them to manage their pain and its impact more effectively before surgery. However, studies of arthritis self-management programmes have faced challenges because of low recruitment rates, poor intervention uptake, and high attrition rates. This study aimed to evaluate the feasibility of a randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of a group-based pain self-management course for patients undergoing THR. Specific objectives were to assess trial design, ascertain recruitment and retention rates, identify barriers to participation, refine data collection methods, and evaluate uptake and patient satisfaction with the course.

Patients listed for THR in an elective orthopaedic centre Bristol, UK were sent a postal invitation about the study. Participants were randomised to attend a pain self-management course plus standard care or standard care only using a computer-generated randomisation system. The pain self-management course was delivered by Arthritis Care and consisted of two half-day group sessions prior to surgery and one full-day group session 2–4 months after surgery. A structured course evaluation questionnaire was completed by participants.

Outcomes assessment was by postal questionnaire prior to surgery and 1-month, 3-months and 6-months after surgery. Self-report resource use data were collected using a diary prior to surgery and inclusion of resource use questions in the 3-month and 6-month post-operative questionnaires. Brief telephone interviews were conducted with non-participants to explore barriers to participation.

Postal invitations were sent to 385 eligible patients and 88 patients consented to participate (23% recruitment rate). Participants had a mean age of 66 years and 65% were female. Brief interviews with 57 non-participants revealed the most common reasons for non-participation were perceptions about the intervention and difficulties in getting to the hospital for the course.

Of the 43 patients randomised to the intervention group, 28 attended the pre-operative pain self-management sessions and 11 attended the post-operative sessions. Participant satisfaction with the course was high, and patients enjoyed the group format.

Retention of participants was acceptable, with 83% completing follow-up. Questionnaire return rates were high (76–93%), with the exception of the pre-operative resource use diary (35%). Completion rates for the resource use questions varied by category and allowed for an economic perspective from the health and social care payer to be taken.

Undertaking feasibility work for a RCT is labour-intensive; however this study highlights the importance of conducting such work. Postal recruitment resulted in a low recruitment rate and brief interviews with non-participants provided valuable information on barriers to participation. Embedding collection of resource use data within questionnaires resulted in higher completion rates than using resource use diaries. While patients who attended the course gave positive feedback, attendance was low. Findings from this feasibility study enable us to design successful definitive group-based RCTs in the future.