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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_16 | Pages 3 - 3
19 Aug 2024
Lenguerrand E Whitehouse MR Beswick AD Kunutsor SK Webb JCJ Mehendale S Porter M Blom AW
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We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty. Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies. In total, 535 primary hip arthroplasties were revised with single-stage procedure (1,525 person-years) and 1,605 with two-stage procedure (5,885 person-years). All-cause re-revision was higher following single-stage revision, especially in the first three months (HR at 3 months = 1.98 (95% confidence interval (CI) 1.14 to 3.43), p = 0.009). The risks were comparable thereafter. Re-revision for PJI was higher in the first three postoperative months for single-stage revision and waned with time (HR at 3 months = 1.81 (95% CI 1.22 to 2.68), p = 0.003; HR at 6 months = 1.25 (95% CI 0.71 to 2.21), p = 0.441; HR at 12 months = 0.94 (95% CI 0.54 to 1.63), p = 0.819). Patients initially managed with a single-stage revision received fewer revision operations (mean 1.3 (SD 0.7) vs 2.2 (SD 0.6), p < 0.001). Mortality rates were comparable between these two procedures (29/10,000 person-years vs 33/10,000). The risk of unplanned re-revision was lower following two-stage revision, but only in the early postoperative period. The lower overall number of revision procedures associated with a single-stage revision strategy and the equivalent mortality rates to two-stage revision are reassuring. With appropriate counselling, single-stage revision is a viable option for the treatment of hip PJI.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 464 - 478
3 Jun 2024
Boon A Barnett E Culliford L Evans R Frost J Hansen-Kaku Z Hollingworth W Johnson E Judge A Marques EMR Metcalfe A Navvuga P Petrie MJ Pike K Wylde V Whitehouse MR Blom AW Matharu GS

Aims

During total knee replacement (TKR), surgeons can choose whether or not to resurface the patella, with advantages and disadvantages of each approach. Recently, the National Institute for Health and Care Excellence (NICE) recommended always resurfacing the patella, rather than never doing so. NICE found insufficient evidence on selective resurfacing (surgeon’s decision based on intraoperative findings and symptoms) to make recommendations. If effective, selective resurfacing could result in optimal individualized patient care. This protocol describes a randomized controlled trial to evaluate the clinical and cost-effectiveness of primary TKR with always patellar resurfacing compared to selective patellar resurfacing.

Methods

The PAtellar Resurfacing Trial (PART) is a patient- and assessor-blinded multicentre, pragmatic parallel two-arm randomized superiority trial of adults undergoing elective primary TKR for primary osteoarthritis at NHS hospitals in England, with an embedded internal pilot phase (ISRCTN 33276681). Participants will be randomly allocated intraoperatively on a 1:1 basis (stratified by centre and implant type (cruciate-retaining vs cruciate-sacrificing)) to always resurface or selectively resurface the patella, once the surgeon has confirmed sufficient patellar thickness for resurfacing and that constrained implants are not required. The primary analysis will compare the Oxford Knee Score (OKS) one year after surgery. Secondary outcomes include patient-reported outcome measures at three months, six months, and one year (Knee injury and Osteoarthritis Outcome Score, OKS, EuroQol five-dimension five-level questionnaire, patient satisfaction, postoperative complications, need for further surgery, resource use, and costs). Cost-effectiveness will be measured for the lifetime of the patient. Overall, 530 patients will be recruited to obtain 90% power to detect a four-point difference in OKS between the groups one year after surgery, assuming up to 40% resurfacing in the selective group.


Bone & Joint Research
Vol. 12, Issue 5 | Pages 321 - 330
9 May 2023
Lenguerrand E Whitehouse MR Beswick AD Kunutsor SK Webb JCJ Mehendale S Porter M Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage and single-stage revision surgeries among patients with infected primary hip arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary arthroplasty revised with single-stage or two-stage procedure in England and Wales between 2003 and 2014 were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HRs) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


Bone & Joint Open
Vol. 4, Issue 4 | Pages 226 - 233
1 Apr 2023
Moore AJ Wylde V Whitehouse MR Beswick AD Walsh NE Jameson C Blom AW

Aims

Periprosthetic hip-joint infection is a multifaceted and highly detrimental outcome for patients and clinicians. The incidence of prosthetic joint infection reported within two years of primary hip arthroplasty ranges from 0.8% to 2.1%. Costs of treatment are over five-times greater in people with periprosthetic hip joint infection than in those with no infection. Currently, there are no national evidence-based guidelines for treatment and management of this condition to guide clinical practice or to inform clinical study design. The aim of this study is to develop guidelines based on evidence from the six-year INFection and ORthopaedic Management (INFORM) research programme.

Methods

We used a consensus process consisting of an evidence review to generate items for the guidelines and online consensus questionnaire and virtual face-to-face consensus meeting to draft the guidelines.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 690 - 699
4 Oct 2022
Lenguerrand E Whitehouse MR Kunutsor SK Beswick AD Baker RP Rolfson O Reed MR Blom AW

Aims

We compared the risks of re-revision and mortality between two-stage revision surgery and single-stage revision surgery among patients with infected primary knee arthroplasty.

Methods

Patients with a periprosthetic joint infection (PJI) of their primary knee arthroplasty, initially revised with a single-stage or a two-stage procedure in England and Wales between 2003 and 2014, were identified from the National Joint Registry. We used Poisson regression with restricted cubic splines to compute hazard ratios (HR) at different postoperative periods. The total number of revisions and re-revisions undergone by patients was compared between the two strategies.


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1052 - 1059
1 Sep 2022
Penfold CM Judge A Sayers A Whitehouse MR Wilkinson JM Blom AW

Aims

Our main aim was to describe the trend in the comorbidities of patients undergoing elective total hip arthroplasties (THAs) and knee arthroplasties (KAs) between 1 January 2005 and 31 December 2018 in England.

Methods

We combined data from the National Joint Registry (NJR) on primary elective hip and knee arthroplasties performed between 2005 and 2018 with pre-existing conditions recorded at the time of their primary operation from Hospital Episodes Statistics. We described the temporal trend in the number of comorbidities identified using the Charlson Comorbidity Index, and how this varied by age, sex, American Society of Anesthesiologists (ASA) grade, index of multiple deprivation, and type of KA.


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 359 - 367
1 Mar 2022
Deere K Matharu GS Ben-Shlomo Y Wilkinson JM Blom AW Sayers A Whitehouse MR

Aims

A recent report from France suggested an association between the use of cobalt-chrome (CoCr) femoral heads in total hip arthroplasties (THAs) and an increased risk of dilated cardiomyopathy and heart failure. CoCr is a commonly used material in orthopaedic implants. If the reported association is causal, the consequences would be significant given the millions of joint arthroplasties and other orthopaedic procedures in which CoCr is used annually. We examined whether CoCr-containing THAs were associated with an increased risk of all-cause mortality, heart outcomes, cancer, and neurodegenerative disorders in a large national database.

Methods

Data from the National Joint Registry was linked to NHS English hospital inpatient episodes for 374,359 primary THAs with up to 14.5 years' follow-up. We excluded any patients with bilateral THAs, knee arthroplasties, indications other than osteoarthritis, aged under 55 years, and diagnosis of one or more outcome of interest before THA. Implants were grouped as either containing CoCr or not containing CoCr. The association between implant construct and the risk of all-cause mortality and incident heart failure, cancer, and neurodegenerative disorders was examined.


The Bone & Joint Journal
Vol. 104-B, Issue 3 | Pages 341 - 351
1 Mar 2022
Fowler TJ Aquilina AL Reed MR Blom AW Sayers A Whitehouse MR

Aims

Total hip arthroplasties (THAs) are performed by surgeons at various stages in training with varying levels of supervision, but we do not know if this is safe practice with comparable outcomes to consultant-performed THA. Our aim was to examine the association between surgeon grade, the senior supervision of trainees, and the risk of revision following THA.

Methods

We performed an observational study using National Joint Registry (NJR) data. We included adult patients who underwent primary THA for osteoarthritis, recorded in the NJR between 2003 and 2016. Exposures were operating surgeon grade (consultant or trainee) and whether or not trainees were directly supervised by a scrubbed consultant. Outcomes were all-cause revision and the indication for revision up to ten years. We used methods of survival analysis, adjusted for patient, operation, and healthcare setting factors.


The Bone & Joint Journal
Vol. 103-B, Issue 5 | Pages 864 - 871
3 May 2021
Hunt LP Matharu GS Blom AW Howard PW Wilkinson JM Whitehouse MR

Aims

Debate remains whether the patella should be resurfaced during total knee replacement (TKR). For non-resurfaced TKRs, we estimated what the revision rate would have been if the patella had been resurfaced, and examined the risk of re-revision following secondary patellar resurfacing.

Methods

A retrospective observational study of the National Joint Registry (NJR) was performed. All primary TKRs for osteoarthritis alone performed between 1 April 2003 and 31 December 2016 were eligible (n = 842,072). Patellar resurfacing during TKR was performed in 36% (n = 305,844). The primary outcome was all-cause revision surgery. Secondary outcomes were the number of excess all-cause revisions associated with using TKRs without (versus with) patellar resurfacing, and the risk of re-revision after secondary patellar resurfacing.


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_4 | Pages 56 - 56
1 Mar 2021
Moore AJ Palmer C Mallon C Gooberman-Hill R Whitehouse MR Blom AW
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Prosthetic joint infection (PJI) is an uncommon but serious complication of hip replacement. Over 1,000 operations are performed annually in the United Kingdom for PJI following hip replacement, using either one- or two-stage revision arthroplasty. It is unclear which is preferred by patients and which has the best long-term outcome. This qualitative study aims to describe patient experiences of treatment and recovery following one- and two-stage revision arthroplasty for PJI within the context of a pragmatic randomised controlled trial comparing these two approaches. Semi-structured interviews were conducted with 32 patients undergoing one- or two-stage revision treatment for PJI as part of a UK multi-centre randomised controlled trial. Patients were recruited from 12 participating National Health Service (NHS) Orthopaedic Departments and were interviewed 2–4 months after their first revision surgery and again approximately 18 months later. Final sample size was justified on the basis of thematic saturation. All patients consented to the interview being audio-recorded, transcribed, anonymised and analysed using an inductive thematic approach. Ethical approval was provided by NRES Committee South-West Frenchay, 14/SW/116. Patients in both the one- and two-stage treatment groups described prolonged hospital stays, with burdensome antibiotics and brief physiotherapy treatment. However, following discharge home and during recovery, participants undergoing two-stage revision with an ‘empty hip' or with a spacer reported being physically restricted in almost every aspect of their daily life, resulting in inactivity and confinement to home. Mobility aids were not sufficiently available through the health service for these patients. A key difference is that those with a spacer reported more pain than those without. Approximately one year following their second-stage revision, participants described being more independent and active, but two directly attributed muscle weakness to the lengthy period without a hip and described resulting falls or dislocations that had complicated their recovery. In contrast, those undergoing one-stage revision and CUMARS appeared to be more alike, reporting better mobility, functionality and independence, although still limited. Participants in these groups also reported minimal or no pain following their revision. A key difference between CUMARS and one-stage revision was the uncertainty of whether a second operation was necessary, which participants described as “hanging over them”, while those in the two-stage empty hip or spacer group described a more positive anticipation of a second definitive operation as it marked an end to what was described as a detachment from life. Our findings highlight the differences between patient experiences of recovery following revision arthroplasty, and how this is influenced by the surgical approach and presence or lack of spacers. An understanding of lived experiences following one- and two-stage surgical interventions will complement knowledge about the clinical effectiveness of these different types of revision surgery.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 808 - 820
1 Nov 2020
Trela-Larsen L Kroken G Bartz-Johannessen C Sayers A Aram P McCloskey E Kadirkamanathan V Blom AW Lie SA Furnes ON Wilkinson JM

Aims

To develop and validate patient-centred algorithms that estimate individual risk of death over the first year after elective joint arthroplasty surgery for osteoarthritis.

Methods

A total of 763,213 hip and knee joint arthroplasty episodes recorded in the National Joint Registry for England and Wales (NJR) and 105,407 episodes from the Norwegian Arthroplasty Register were used to model individual mortality risk over the first year after surgery using flexible parametric survival regression.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_2 | Pages 27 - 27
1 Jan 2019
Aram P Trela-Larsen L Sayers A Hills AF Blom AW McCloskey EV Kadirkamanathan V Wilkinson JM
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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.

In this comparative study we implemented parametric and flexible parametric (FP) methods and random survival forests (RSF). The overall performance of the parametric models was compared using Akaike information criterion (AIC). The preferred parametric model and the RSF algorithm were further compared in terms of the Brier score, concordance index (C index) and calibration.

The dataset contains 327 238 hip replacements for osteoarthritis carried out in England and Wales between 2003 and 2015. The AIC value for the FP model was the lowest. The averages of survival probability estimates were in good agreement with the observed values for the FP model and the RSF algorithm. The integrated Brier score of the FP model and the RSF approach over 10 years were similar: 0.011 (95% confidence interval: 0.011–0.011). The C index of the FP model at 10 years was 59.4% (95% confidence interval: 59.4%–59.4%). This was 56.2% (56.1%–56.3%) for the RSF method.

The FP model outperformed other commonly used survival models across chosen validation criteria. However, it does not provide high discriminatory power at the individual level. Models with more comprehensive risk adjustment may provide additional insights for individual risk.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 43 - 43
1 Nov 2018
Beswick AD Strange S Mallon C Lenguerrand E Moore AJ Kunutsor SK Whitehouse MR Porteous A Toms A Blom AW
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Patients with knee prosthetic joint infection (PJI) frequently receive one- or two-stage revision. To explore the feasibility of a randomised controlled trial (RCT) comparing methods, we analysed a UK registry, interviewed patients and surgeons, systematically reviewed literature, held a consensus meeting, and assessed progress of an RCT in hip PJI. In 2014, in England and Wales, knee PJI was treated with one- or two-stage procedures in 19% and 71% of patients respectively. Between 2007 and 2014, use of one-stage procedures doubled and, in major centres, up to 42% of treatments were one-stage. We conducted in-depth interviews with 16 patients with knee PJI and 11 surgeons performing one- or two-stage revision. Patients considered randomisation acceptable with appropriate counselling and, depending on infecting organisms and health status, surgeons would randomise treatments. In meta-analysis, two-year re-infection rates in 10 one-stage series (423 patients) and 108 two-stage series (5,129 patients) were 7.6% (95%CI 3.4,13.1) and 8.8% (7.2,10.6) respectively. In a series of patients with knee PJI, surgeons from 2 major centres considered 6/15 patients eligible for either treatment, with 4 more potentially eligible after treatment of soft tissue infection. In an ongoing RCT of surgical treatment of hip PJI, 116 patients have been randomised at 14 centres in 3 years. Randomising patients with PJI is feasible but, as knee PJI is uncommon, a multicentre RCT would be required. Based on WOMAC score outcome and appropriate assumptions on eligibility and acceptability, 170 patients would need to be randomised over 4 years at 14 major centres.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_14 | Pages 2 - 2
1 Nov 2018
Bolink SAAN Lenguerrand E Brunton L Hinds N Wylde V Blom AW Whitehouse M Grimm B
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Restoring native hip anatomy and biomechanics is important to create a well-functioning total hip arthroplasty (THA). Hip offset and leg length are regarded as the most important biomechanical characteristics. This study investigated their association with clinical outcomes including patient reported outcome measures (PROMs) and functional tests. This prospective cohort study was conducted in 77 patients undergoing primary THA (age=65±11 years). Hip offset and leg length were measured on anteroposterior radiographs of the hip pre- and postoperatively. Participants completed the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and performed functional tests (i.e. gait, single leg stance, sit-to-stand, block step-up) preoperatively, and 3 and 12 months postoperatively. A wearable motion sensor was used to derive biomechanical parameters. Associations between radiographic and functional outcomes were investigated with the Spearman's rho correlation coefficient. Subgroup comparisons were conducted for patients with more than 15% decreased or increased femoral offset after THA. Differences in postoperative offset and leg length had little impact on clinical outcomes. Femoral offset subgroups demonstrated no significantly different WOMAC function scores. In functional tests, patients with >15% decreased femoral offset after THA demonstrated more sagittal plane motion during block step-up (14.43° versus 10.66°; p=0.04) while patients with >15% increased femoral after THA demonstrated more asymmetry of frontal plane motion during block step-up (34.05% versus 14.18%; p=0.03). To create a well-functioning THA, there seems to be a reasonable safe zone regarding the reconstruction of offset and leg length.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 12 - 12
1 Apr 2018
Marques EM Blom AW Erik L Vikki W Sian N
Full Access

Background

The Arthroplasty Pain Experience (APEX) studies are two randomised controlled trials in primary total hip (THR) and knee replacement (TKR) at a large UK orthopaedics centre. APEX investigated the effect of local anaesthetic wound infiltration (LAI), administered before wound closure, in addition to standard analgesia, on pain severity at 12 months. This abstract reports results of the within-trial economic evaluations.

Methods

Cost-effectiveness was assessed from the health and social care payer perspective in relation to quality adjusted life years (QALYs). Resource use was collected from hospital records and patient-completed postal questionnaires, and valued using unit cost estimates from local NHS Trust and national tariffs. Missing data were imputed using chained equations. Costs and outcomes were compared per trial arm and plotted in cost-effectiveness planes. The economic results were bootstrapped incremental net monetary benefit statistics (INMB) and cost-effectiveness acceptability curves. One-way deterministic sensitivity analyses explored any methodological uncertainty.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 8 - 8
1 Apr 2018
Marques E Fawsitt C Thom H Hunt LP Nemes S Lopez-Lopez J Beswick A Burston A Higgins JP Hollingworth W Welton NJ Rolfson O Garellick G Blom AW
Full Access

Background

Prosthetic implants used in primary total hip replacements have a range of bearing surface combinations (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, metal-on-metal); head sizes (small <36mm, large 36mm+); and fixation techniques (cemented, uncemented, hybrid, reverse hybrid), which influence prosthesis survival, patient quality of life, and healthcare costs. This study compared the lifetime cost-effectiveness of implants to determine the optimal choice for patients of different age and gender profiles.

Methods

In an economic decision Markov model, the probability that patients required one or more revision surgeries was estimated from analyses of UK and Swedish hip joint registries, for males and females aged <55, 55–64, 65–74, 75–84, and 85+ years. Implant and healthcare costs were estimated from hospital procurement prices, national tariffs, and the literature. Quality-adjusted life years were calculated using utility estimates, taken from Patient-Reported Outcome Measures data for hip procedures in the UK.


The Bone & Joint Journal
Vol. 100-B, Issue 1 | Pages 33 - 41
1 Jan 2018
Matharu GS Hunt LP Murray DW Howard P Pandit HG Blom AW Bolland B Judge A

Aims

The aim of this study was to determine whether the rates of revision for metal-on-metal (MoM) total hip arthroplasties (THAs) with Pinnacle components varied according to the year of the initial operation, and compare these with the rates of revision for other designs of MoM THA.

Patients and Methods

Data from the National Joint Registry for England and Wales included 36 mm MoM THAs with Pinnacle acetabular components which were undertaken between 2003 and 2012 with follow-up for at least five years (n = 10 776) and a control group of other MoM THAs (n = 13 817). The effect of the year of the primary operation on all-cause rates of revision was assessed using Cox regression and interrupted time-series analysis.


Bone & Joint Research
Vol. 6, Issue 6 | Pages 391 - 398
1 Jun 2017
Lenguerrand E Whitehouse MR Beswick AD Jones SA Porter ML Blom* AW

Objectives

We used the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) to investigate the risk of revision due to prosthetic joint infection (PJI) for patients undergoing primary and revision hip arthroplasty, the changes in risk over time, and the overall burden created by PJI.

Methods

We analysed revision total hip arthroplasties (THAs) performed due to a diagnosis of PJI and the linked index procedures recorded in the NJR between 2003 and 2014. The cohort analysed consisted of 623 253 index primary hip arthroplasties, 63 222 index revision hip arthroplasties and 7585 revision THAs performed due to a diagnosis of PJI. The prevalence, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_8 | Pages 89 - 89
1 Apr 2017
Lenguerrand E Wylde V Gooberman-Hill R Sayers A Dieppe P Blom AW
Full Access

Background

While many studies have investigated long-term outcomes after lower limb arthroplasty, rather less is known about the trajectory of short-term outcomes in the first post-operative year. It is difficult for a surgeon to know when, in terms of disease severity, it is best to operate, or to make an accurate prediction of the patient pattern of post-operative recovery. We explored the trajectory of change in pain and function following primary hip and knee arthroplasty and the influence of pre-operative self-reported symptoms on post-operative improvements.

Methods

A prospective UK cohort study of 164 patients undergoing primary hip (n=80) or knee (n=84) arthroplasty. WOMAC pain and function measures were collected pre-operatively and at 3 and 12 months post-operatively. Hip and knee arthroplasties were analysed separately, and patients were split into two groups: those with high or low symptoms pre-operatively. Multilevel regressions were used for each outcome (pain and function), and the trajectory of change (0–3 months and 3–12 months) charted. The study was approved by Southwest 4 Research Ethics Committee (09/H0102/72) and all patients provided informed, written consent. The authors have no competing interests to disclose.


The Bone & Joint Journal
Vol. 98-B, Issue 10 | Pages 1347 - 1354
1 Oct 2016
Palan J Smith MC Gregg P Mellon S Kulkarni A Tucker K Blom AW Murray DW Pandit H

Aims

Periprosthetic fracture (PF) after primary total hip arthroplasty (THA) is an uncommon but potentially devastating complication. This study aims to investigate the influence of cemented stem designs on the risk of needing a revision for a PF.

Patients and Methods

We analysed data on 257 202 primary THAs with cemented stems and 390 linked first revisions for PF recorded in the National Joint Registry (NJR) of England, Wales and Northern Ireland to determine if a cemented femoral stem brand was associated with the risk of having revision for a PF after primary THA. All cemented femoral stem brands with more than 10 000 primary operations recorded in the NJR were identified. The four most commonly used cemented femoral stems were the Exeter V40 (n = 146 409), CPT (n = 24 300), C-Stem (n = 15 113) and Charnley (n = 20 182).

We compared the revision risk ratios due to PF amongst the stems using a Poisson regression model adjusting for patient factors. Compared with the Exeter V40, the age, gender and ASA grade adjusted revision rate ratio was 3.89 for the cemented CPT stem (95% confidence interval (CI) 3.07 to 4.93), 0.89 for the C-Stem (95% CI 0.57 to 1.41) and 0.41 for the Charnley stem (95% CI 0.24 to 0.70).