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Bone & Joint Open
Vol. 5, Issue 11 | Pages 977 - 983
5 Nov 2024
Danielsen O Jensen CB Varnum C Jakobsen T Andersen MR Bieder MJ Overgaard S Jørgensen CC Kehlet H Gromov K Lindberg-Larsen M

Aims

Day-case success rates after primary total hip arthroplasty (THA), total knee arthroplasty (TKA), and medial unicompartmental knee arthroplasty (mUKA) may vary, and detailed data are needed on causes of not being discharged. The aim of this study was to analyze the association between surgical procedure type and successful day-case surgery, and to analyze causes of not being discharged on the day of surgery when eligible and scheduled for day-case THA, TKA, and mUKA.

Methods

A multicentre, prospective consecutive cohort study was carried out from September 2022 to August 2023. Patients were screened for day-case eligibility using well defined inclusion and exclusion criteria, and discharged when fulfilling predetermined discharge criteria. Day-case eligible patients were scheduled for surgery with intended start of surgery before 1.00 pm.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 837 - 843
7 Oct 2024
Zalikha AK Waheed MA Twal C Keeley J El-Othmani MM Hajj Hussein I

Aims

This study aims to evaluate the impact of metabolic syndrome in the setting of obesity on in-hospital outcomes and resource use after total joint replacement (TJR).

Methods

A retrospective analysis was conducted using the National Inpatient Sample from 2006 to the third quarter of 2015. Discharges representing patients aged 40 years and older with obesity (BMI > 30 kg/m2) who underwent primary TJR were included. Patients were stratified into two groups with and without metabolic syndrome. The inverse probability of treatment weighting (IPTW) method was used to balance covariates.


Bone & Joint Open
Vol. 5, Issue 10 | Pages 832 - 836
4 Oct 2024
Kayani B Mancino F Baawa-Ameyaw J Roussot MA Haddad FS

Aims

The outcomes of patients with unexpected positive cultures (UPCs) during revision total hip arthroplasty (THA) and total knee arthroplasty (TKA) remain unknown. The objectives of this study were to establish the prevalence and infection-free implant survival in UPCs during presumed aseptic single-stage revision THA and TKA at mid-term follow-up.

Methods

This study included 297 patients undergoing presumed aseptic single-stage revision THA or TKA at a single treatment centre. All patients with at least three UPCs obtained during revision surgery were treated with minimum three months of oral antibiotics following revision surgery. The prevalence of UPCs and causative microorganisms, the recurrence of periprosthetic joint infections (PJIs), and the infection-free implant survival were established at minimum five years’ follow-up (5.1 to 12.3).


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1084 - 1092
1 Oct 2024
Hammat AS Nelson R Davis JS Manning L Campbell D Solomon LB Gnanamanickam ES Callary SA

Aims

Our aim was to estimate the total costs of all hospitalizations for treating periprosthetic joint infection (PJI) by main management strategy within 24 months post-diagnosis using activity-based costing. Additionally, we investigated the influence of individual PJI treatment pathways on hospital costs within the first 24 months.

Methods

Using admission and procedure data from a prospective observational cohort in Australia and New Zealand, Australian Refined Diagnosis Related Groups were assigned to each admitted patient episode of care for activity-based costing estimates of 273 hip PJI patients and 377 knee PJI patients. Costs were aggregated at 24 months post-diagnosis, and are presented in Australian dollars.


The Bone & Joint Journal
Vol. 106-B, Issue 10 | Pages 1074 - 1083
1 Oct 2024
Sørensen RR Timm S Rasmussen LE Brasen CL Varnum C

Aims

The influence of metabolic syndrome (MetS) on the outcome after hip and knee arthroplasty is debated. We aimed to investigate the change in patient-reported outcome measure (PROM) scores after hip and knee arthroplasty, comparing patients with and without MetS.

Methods

From 1 May 2017 to 30 November 2019, a prospective cohort of 2,586 patients undergoing elective unilateral hip and knee arthroplasty was established in Denmark. Data from national registries and a local database were used to determine the presence of MetS. Patients’ scores on Oxford Hip Score (OHS) or Oxford Knee Score (OKS), EuroQol five-dimension five-level questionnaire (EQ-5D-5L), University of California, Los Angeles (UCLA) Activity Scale, and Forgotten Joint Score (FJS) at baseline, three, 12, and 24 months after surgery were collected. Primary outcome was the difference between groups from baseline to 12 months in OHS and OKS. Secondary outcomes were scores of OHS and OKS at three and 24 months and EQ-5D-5L, UCLA Activity Scale, and FJS at three, 12, and 24 months after surgery. Generalized linear mixed model was applied, adjusting for age, sex, Charlson Comorbidity Index, and smoking to present marginal mean and associated 95% CIs.


Bone & Joint Open
Vol. 5, Issue 9 | Pages 785 - 792
19 Sep 2024
Clement RGE Wong SJ Hall A Howie SEM Simpson AHRW

Aims

The aims of this study were to: 1) report on a cohort of skeletally mature patients with native hip and knee septic arthritis over a 14-year period; 2) to determine the rate of joint failure in patients who had experienced an episode of hip or knee septic arthritis; and 3) to assess the outcome following septic arthritis relative to the infecting organism, whether those patients infected by Staphylococcus aureus would be more likely to have adverse outcomes than those infected by other organisms.

Methods

All microbiological samples from joint aspirations between March 2000 and December 2014 at our institution were reviewed in order to identify cases of culture-proven septic arthritis. Cases in children (aged < 16 years) and prosthetic joints were excluded. Data were abstracted on age at diagnosis, sex, joint affected (hip or knee), type of organisms isolated, cause of septic arthritis, comorbidities within the Charlson Comorbidity Index (CCI), details of treatment, and outcome.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 924 - 934
1 Sep 2024
Cheok T Beveridge A Berman M Coia M Campbell A Tse TTS Doornberg JN Jaarsma RL

Aims

We investigated the efficacy and safety profile of commonly used venous thromboembolism (VTE) prophylaxis agents following hip and knee arthroplasty.

Methods

A systematic search of PubMed, Embase, Cochrane Library, Web of Science, and OrthoSearch was performed. Prophylaxis agents investigated were aspirin (< 325 mg and ≥ 325 mg daily), enoxaparin, dalteparin, fondaparinux, unfractionated heparin, warfarin, rivaroxaban, apixaban, and dabigatran. The primary efficacy outcome of interest was the risk of VTE, whereas the primary safety outcomes of interest were the risk of major bleeding events (MBE) and wound complications (WC). VTE was defined as the confirmed diagnosis of any deep vein thrombosis and/or pulmonary embolism. Network meta-analysis combining direct and indirect evidence was performed. Cluster rank analysis using the surface under cumulative ranking (SUCRA) was applied to compare each intervention group, weighing safety and efficacy outcomes.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 935 - 941
1 Sep 2024
Ailaney N Guirguis PG Ginnetti JG Balkissoon R Myers TG Ramirez G Thirukumaran CP Ricciardi BF

Aims. The purpose of this study was to determine the association between prior sleeve gastrectomy in patients undergoing primary total hip and knee arthroplasty, and 90-day complications, incidence of revision arthroplasty, and patient-reported outcome scores at final follow-up. Methods. This is a retrospective, single-centre analysis. Patients undergoing primary hip or knee arthroplasty with a prior sleeve gastrectomy were eligible for inclusion (n = 80 patients). A morbidly obese control group was established from the same institutional registry using a 1:2 match, for cases:controls with arthroplasty based on propensity score using age, sex, pre-sleeve gastrectomy BMI, Current Procedural Terminology code to identify anatomical location, and presurgical haemoglobin A1C. Outcomes included 90-day complications, incidence of revision arthroplasty, and patient-reported outcome scores at final follow-up. Multivariable logistic regressions evaluated associations of underlying preoperative demographic and treatment characteristics with outcomes. Results. Complications within 90 days of surgery were increased in the sleeve gastrectomy group relative to the obese control group after controlling for underlying preoperative demographic characteristics (odds ratio (OR) 4.00 (95% CI 1.14 to 13.9); p = 0.030). Postoperative revisions were similar in the sleeve gastrectomy group relative to the obese control group after controlling for underlying preoperative demographic characteristics (OR 17.8 (95% CI 0.64 to 494.3); p = 0.090). Patient-Reported Outcomes Measurement Information System (PROMIS) depression decreased by a greater amount from pre- to postoperative in the obese controls relative to the sleeve gastrectomy group (OR 4.04 (95% CI 0.06 to 8.02); p = 0.047). PROMIS pain interference and physical function change from pre- to postoperative was not associated with sleeve gastrectomy status. Conclusion. We found a higher rate of complications at 90 days in patients who underwent sleeve gastrectomy prior to primary hip or knee arthroplasty relative to a matched, obese control population. Prosthetic revision rates were similar between the two groups, while improvements in PROMIS depression scores were larger in the obese cohort. This study suggests that sleeve gastrectomy to achieve preoperative weight loss prior to arthroplasty surgery may not mitigate early complication risks in obese patient populations. Cite this article: Bone Joint J 2024;106-B(9):935–941


The Bone & Joint Journal
Vol. 106-B, Issue 8 | Pages 834 - 841
1 Aug 2024
French JMR Deere K Jones T Pegg DJ Reed MR Whitehouse MR Sayers A

Aims. The COVID-19 pandemic has disrupted the provision of arthroplasty services in England, Wales, and Northern Ireland. This study aimed to quantify the backlog, analyze national trends, and predict time to recovery. Methods. We performed an analysis of the mandatory prospective national registry of all independent and publicly funded hip, knee, shoulder, elbow, and ankle replacements in England, Wales, and Northern Ireland between January 2019 and December 2022 inclusive, totalling 729,642 operations. The deficit was calculated per year compared to a continuation of 2019 volume. Total deficit of cases between 2020 to 2022 was expressed as a percentage of 2019 volume. Sub-analyses were performed based on procedure type, country, and unit sector. Results. Between January 2020 and December 2022, there was a deficit of 158,994 joint replacements. This is equivalent to over two-thirds of a year of normal expected operating activity (71.6%). There were 104,724 (-47.1%) fewer performed in 2020, 41,928 (-18.9%) fewer performed in 2021, and 12,342 (-5.6%) fewer performed in 2022, respectively, than in 2019. Independent-sector procedures increased to make it the predominant arthroplasty provider (53% in 2022). NHS activity was 73.2% of 2019 levels, while independent activity increased to 126.8%. Wales (-136.3%) and Northern Ireland (-121.3%) recorded deficits of more than a year’s worth of procedures, substantially more than England (-66.7%). It would take until 2031 to eliminate this deficit with an immediate expansion of capacity over 2019 levels by 10%. Conclusion. The arthroplasty deficit following the COVID-19 pandemic is now equivalent to over two-thirds of a year of normal operating activity, and continues to increase. Patients awaiting different types of arthroplasty, in each country, have been affected disproportionately. A rapid and significant expansion in services is required to address the deficit, and will still take many years to rectify. Cite this article: Bone Joint J 2024;106-B(8):834–841


Bone & Joint Open
Vol. 5, Issue 7 | Pages 601 - 611
18 Jul 2024
Azarboo A Ghaseminejad-Raeini A Teymoori-Masuleh M Mousavi SM Jamalikhah-Gaskarei N Hoveidaei AH Citak M Luo TD

Aims

The aim of this meta-analysis was to determine the pooled incidence of postoperative urinary retention (POUR) following total hip and knee arthroplasty (total joint replacement (TJR)) and to evaluate the risk factors and complications associated with POUR.

Methods

Two authors conducted searches in PubMed, Embase, Web of Science, and Scopus on TJR and urinary retention. Eligible studies that reported the rate of POUR and associated risk factors for patients undergoing TJR were included in the analysis. Patient demographic details, medical comorbidities, and postoperative outcomes and complications were separately analyzed. The effect estimates for continuous and categorical data were reported as standardized mean differences (SMDs) and odds ratios (ORs) with 95% CIs, respectively.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 688 - 695
1 Jul 2024
Farrow L Zhong M Anderson L

Aims. To examine whether natural language processing (NLP) using a clinically based large language model (LLM) could be used to predict patient selection for total hip or total knee arthroplasty (THA/TKA) from routinely available free-text radiology reports. Methods. Data pre-processing and analyses were conducted according to the Artificial intelligence to Revolutionize the patient Care pathway in Hip and knEe aRthroplastY (ARCHERY) project protocol. This included use of de-identified Scottish regional clinical data of patients referred for consideration of THA/TKA, held in a secure data environment designed for artificial intelligence (AI) inference. Only preoperative radiology reports were included. NLP algorithms were based on the freely available GatorTron model, a LLM trained on over 82 billion words of de-identified clinical text. Two inference tasks were performed: assessment after model-fine tuning (50 Epochs and three cycles of k-fold cross validation), and external validation. Results. For THA, there were 5,558 patient radiology reports included, of which 4,137 were used for model training and testing, and 1,421 for external validation. Following training, model performance demonstrated average (mean across three folds) accuracy, F1 score, and area under the receiver operating curve (AUROC) values of 0.850 (95% confidence interval (CI) 0.833 to 0.867), 0.813 (95% CI 0.785 to 0.841), and 0.847 (95% CI 0.822 to 0.872), respectively. For TKA, 7,457 patient radiology reports were included, with 3,478 used for model training and testing, and 3,152 for external validation. Performance metrics included accuracy, F1 score, and AUROC values of 0.757 (95% CI 0.702 to 0.811), 0.543 (95% CI 0.479 to 0.607), and 0.717 (95% CI 0.657 to 0.778) respectively. There was a notable deterioration in performance on external validation in both cohorts. Conclusion. The use of routinely available preoperative radiology reports provides promising potential to help screen suitable candidates for THA, but not for TKA. The external validation results demonstrate the importance of further model testing and training when confronted with new clinical cohorts. Cite this article: Bone Joint J 2024;106-B(7):688–695


Aims. The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial. Methods. This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years. Results. The CRISTAL trial found that enoxaparin was more effective than aspirin in preventing symptomatic VTE within 90 days of THA or TKA (risk difference 1.97% (95% confidence interval (CI) 0.54% to 3.41%; p = 0.007)). The additional cost after a THA or TKA was AUD$83 (95% CI 68 to 97) for enoxaparin, and enoxaparin resulted in an additional 0.002 QALYs (95% CI -0.002 to 0.005). Incremental cost per QALY gained was AUD$50,567 (95% CI 15,513, dominated) for enoxaparin. We can be 60% confident that the incremental cost per QALY does not exceed the willingness-to-pay threshold of AUD$70,000. Increasing the cost of VTE treatment and extension of costs and consequences to two years suggested greater confidence that enoxaparin is good value for money (70% and 63% confidence, respectively). Conclusion. This analysis provides strong evidence that enoxaparin thromboprophylaxis following THA or TKA reduced VTEs, but weak evidence of net economic benefits over aspirin. If the value of avoiding VTEs is high, and there is a strong likelihood of VTE-related health impairments, we can be more confident that enoxaparin is cost-effective compared to aspirin. Cite this article: Bone Joint J 2024;106-B(6):589–595


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 372 - 379
1 Apr 2024
Straub J Staats K Vertesich K Kowalscheck L Windhager R Böhler C

Aims

Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

Methods

We retrospectively collected data from 226 patients (90 hips, 136 knees) with periprosthetic joint infection who underwent two-stage revision between August 2011 and September 2021, with a minimum follow-up of one year. Histology was assessed via the SLIM classification. First, we analyzed whether patients with positive permanent sections at reimplantation had higher reinfection rates than patients with negative histology. Further, we compared permanent and frozen section results, and assessed the influence of anatomical regions (knee versus hip), low- versus high-grade infections, as well as first revision versus multiple prior revisions on the histological result at reimplantation. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), chi-squared tests, and Kaplan-Meier estimates were calculated.


The Bone & Joint Journal
Vol. 106-B, Issue 4 | Pages 365 - 371
1 Apr 2024
Ledford CK Shirley MB Spangehl MJ Berry DJ Abdel MP

Aims. Breast cancer survivors have known risk factors that might influence the results of total hip arthroplasty (THA) or total knee arthroplasty (TKA). This study evaluated clinical outcomes of patients with breast cancer history after primary THA and TKA. Methods. Our total joint registry identified patients with breast cancer history undergoing primary THA (n = 423) and TKA (n = 540). Patients were matched 1:1 based upon age, sex, BMI, procedure (hip or knee), and surgical year to non-breast cancer controls. Mortality, implant survival, and complications were assessed via Kaplan-Meier methods. Clinical outcomes were evaluated via Harris Hip Scores (HHSs) or Knee Society Scores (KSSs). Mean follow-up was six years (2 to 15). Results. Breast cancer patient survival at five years was 92% (95% confidence interval (CI) 89% to 95%) after THA and 94% (95% CI 92% to 97%) after TKA. Breast and non-breast cancer patients had similar five-year implant survival free of any reoperation or revision after THA (p ≥ 0.412) and TKA (p ≥ 0.271). Breast cancer patients demonstrated significantly lower survival free of any complications after THA (91% vs 96%, respectively; hazard ratio = 2 (95% CI 1.1 to 3.4); p = 0.017). Specifically, the rate of intraoperative fracture was 2.4% vs 1.4%, and venous thromboembolism (VTE) was 1.4% and 0.5% for breast cancer and controls, respectively, after THA. No significant difference was noted in any complications after TKA (p ≥ 0.323). Both breast and non-breast cancer patients experienced similar improvements in HHSs (p = 0.514) and KSSs (p = 0.132). Conclusion. Breast cancer survivors did not have a significantly increased risk of mortality or reoperation after primary THA and TKA. However, there was a two-fold increased risk of complications after THA, including intraoperative fracture and VTE. Cite this article: Bone Joint J 2024;106-B(4):365–371


Bone & Joint Open
Vol. 5, Issue 2 | Pages 139 - 146
15 Feb 2024
Wright BM Bodnar MS Moore AD Maseda MC Kucharik MP Diaz CC Schmidt CM Mir HR

Aims

While internet search engines have been the primary information source for patients’ questions, artificial intelligence large language models like ChatGPT are trending towards becoming the new primary source. The purpose of this study was to determine if ChatGPT can answer patient questions about total hip (THA) and knee arthroplasty (TKA) with consistent accuracy, comprehensiveness, and easy readability.

Methods

We posed the 20 most Google-searched questions about THA and TKA, plus ten additional postoperative questions, to ChatGPT. Each question was asked twice to evaluate for consistency in quality. Following each response, we responded with, “Please explain so it is easier to understand,” to evaluate ChatGPT’s ability to reduce response reading grade level, measured as Flesch-Kincaid Grade Level (FKGL). Five resident physicians rated the 120 responses on 1 to 5 accuracy and comprehensiveness scales. Additionally, they answered a “yes” or “no” question regarding acceptability. Mean scores were calculated for each question, and responses were deemed acceptable if ≥ four raters answered “yes.”


Bone & Joint Open
Vol. 5, Issue 1 | Pages 60 - 68
24 Jan 2024
Shawon MSR Jin X Hanly M de Steiger R Harris I Jorm L

Aims

It is unclear whether mortality outcomes differ for patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) surgery who are readmitted to the index hospital where their surgery was performed, or to another hospital.

Methods

We analyzed linked hospital and death records for residents of New South Wales, Australia, aged ≥ 18 years who had an emergency readmission within 90 days following THA or TKA surgery between 2003 and 2022. Multivariable modelling was used to identify factors associated with non-index readmission and to evaluate associations of readmission destination (non-index vs index) with 90-day and one-year mortality.


The Bone & Joint Journal
Vol. 105-B, Issue 12 | Pages 1294 - 1302
1 Dec 2023
Knoll L Steppacher SD Furrer H Thurnheer-Zürcher MC Renz N

Aims

A higher failure rate has been reported in haematogenous periprosthetic joint infection (PJI) compared to non-haematogenous PJI. The reason for this difference is unknown. We investigated the outcome of haematogenous and non-haematogenous PJI to analyze the risk factors for failure in both groups of patients.

Methods

Episodes of knee or hip PJI (defined by the European Bone and Joint Infection Society criteria) treated at our institution between January 2015 and October 2020 were included in a retrospective PJI cohort. Episodes with a follow-up of > one year were stratified by route of infection into haematogenous and non-haematogenous PJI. Probability of failure-free survival was estimated using the Kaplan-Meier method, and compared between groups using log-rank test. Univariate and multivariate analysis was applied to assess risk factors for failure.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 899 - 905
24 Nov 2023
Orfanos G Nantha Kumar N Redfern D Burston B Banerjee R Thomas G

Aims

We aim to evaluate the usefulness of postoperative blood tests by investigating the incidence of abnormal results following total joint replacement (TJR), as well as identifying preoperative risk factors for abnormal blood test results postoperatively, especially pertaining to anaemia and acute kidney injury (AKI).

Methods

This is a retrospective cohort study of patients who had elective TJR between January and December 2019 at a tertiary centre. Data gathered included age at time of surgery, sex, BMI, American Society of Anesthesiologists (ASA) grade, preoperative and postoperative laboratory test results, haemoglobin (Hgb), white blood count (WBC), haematocrit (Hct), platelets (Plts), sodium (Na+), potassium (K+), creatinine (Cr), estimated glomerular filtration rate (eGFR), and Ferritin (ug/l). Abnormal blood tests, AKI, electrolyte imbalance, anaemia, transfusion, reoperation, and readmission within one year were reported.


Bone & Joint Open
Vol. 4, Issue 10 | Pages 742 - 749
6 Oct 2023
Mabrouk A Abouharb A Stewart G Palan J Pandit H

Aims

Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance.

Methods

The guidelines for the primary and alternative recommended prophylactic antibiotic regimens in clean orthopaedic surgery (primary arthroplasty) for 109 hospitals and trusts across the UK were sought by searching each trust and hospital’s website (intranet webpages), and by using the MicroGuide app. The mean cost of each antibiotic regimen was calculated using price data from the British National Formulary (BNF). Regimens were then compared to the 2018 Philadelphia Consensus Guidance, to evaluate adherence to international guidance.


The Bone & Joint Journal
Vol. 105-B, Issue 9 | Pages 977 - 984
1 Sep 2023
Kamp T Gademan MGJ van Zon SKR Nelissen RGHH Vliet Vlieland TPM Stevens M Brouwer S

Aims

For the increasing number of working-age patients undergoing total hip or total knee arthroplasty (THA/TKA), return to work (RTW) after surgery is crucial. We investigated the association between occupational class and time to RTW after THA or TKA.

Methods

Data from the prospective multicentre Longitudinal Leiden Orthopaedics Outcomes of Osteoarthritis Study were used. Questionnaires were completed preoperatively and six and 12 months postoperatively. Time to RTW was defined as days from surgery until RTW (full or partial). Occupational class was preoperatively assessed and categorized into four categories according to the International Standard Classification of Occupations 2008 (blue-/white-collar, high-/low-skilled). Cox regression analyses were conducted separately for THA and TKA patients. Low-skilled blue-collar work was used as the reference category.