Title: Infection after total joint replacement
Funder: Department of Health and Social Care

Abstract: Aims and Objectives The overall aim of the programme is to improve treatment of patients with deep prosthetic joint infection after total hip or knee joint replacement. Background and rationale Deep prosthetic joint infection (PJI) is a serious complication of total joint replacement (TJR) causing severe pain, poor quality of life and, if untreated, disability, amputation and death. UK incidence is about 1% necessitating around 2000 complex surgical procedures per year. Surgical revision involves prosthesis removal, debridement, antibiotic treatment and replacement. The prosthesis is replaced in the same operation (1-stage) or delayed for 3-6 months (2-stage). 2-stage revision allows additional antimicrobial strategies but mobility and quality of life are poor between stages and further surgery is required. About 10% of patients have re-infection within 2 years. The surgical treatment with lowest re-infection risk is unclear with decisions largely based on surgeon preference. UK estimates are that 26% of patients receive 1-stage and 70% 2-stage revision. Research environment Four tertiary referral centres treating PJI will participate with Avon Orthopaedic Centre coordination. We have expertise conducting large randomised trials and application of research methods in the orthopaedic setting. Research plan A programme of 7 work packages (WP) aims to improve treatment of PJI after TJR. Work packages will have patient forum input throughout. WP1. Systematic reviews and individual patient data meta-analyses will compare re-infection after surgical strategies. Evidence on prediction, diagnosis and monitoring will be reviewed. WP2. Analysis of National Joint Registry data will identify predictors of PJI and determine whether treatment is more successful in high volume specialist centres. WP3. Qualitative in-depth interviews will study the impact on patients of PJI and treatment, and will help refine methods for treatment evaluation. WP4. In a multicentre randomised trial we will compare 1- and 2-stage surgical revision of hip PJI. Patients will be eligible if the treating surgeon believes either treatment appropriate. Primary outcomes will include patient-centred measures. WP5. Treatment costs will be estimated and effects of patient- and hospital-specific factors estimated with statistical modelling. Economic implications of 1- and 2-stage revision for hip PJI will be assessed from a societal perspective. WP6. Patients' preferences for surgical revision of PJI will be explored using discrete choice methods. We will assess trade-offs that patients are willing to make between patient-centred and clinical outcomes, and explore how treatment strategies change preferences for outcomes. WP7. The programme will disseminate evidence on best practice, including cost effectiveness, conferring benefits to patients and NHS. Projected Outputs & Dissemination plans By addressing effectiveness and acceptability, the programme is well-placed to recommend improvements to care and deliver: Reviews and meta-analyses of PJI treatment, predictors and diagnosis by year 4 Predictors of PJI and effect of surgeon and unit volume on outcomes by year 3 Evidence on patient impact of PJI by year 4 Evidence from a randomised trial on treatment effectiveness by year 5 Information on cost impact of treatments by year 5 Knowledge on trade-offs between patient-reported and clinical outcomes in the context of 1- and 2-stage revision by year 5 The findings will inform: Patients We will establish how care and outcomes can be optimised after PJI. Guidance material developed with Arthritis Care, programme patient group, health promotion professionals and press offices will enable patients to maximise recovery in partnership with the NHS. Clinicians Evidence on improving care and outcomes will affect clinical practice. We will present findings at conferences and in peer-reviewed journals, and develop training materials. Stakeholders In partnership with stakeholders we will develop guidance on best practice for treating PJI. Relevant expertise & experience of the research team The programme team are experienced in health services research, musculoskeletal medicine and infection. Links between groups are established with numerous collaborations. Ongoing research explores outcome measures important to patients. Patient and public involvement is incorporated extensively into current research. Justification of costs New research posts will implement the programme. Key roles include research nurses in each centre, qualitative researcher, systematic reviewer, statistician, economist and study coordinator. Patient and public involvement will be implemented by an experienced coordinator and Arthritis Research. Overall supervision will be by the principal investigator with co-applicants providing specialist inputs into study design, conduct and analysis. Management & Governance, including Programme Management and any ethical implications The programme will be sponsored and managed by North Bristol NHS Trust. The Principal Investigator will take overall programme responsibility with a surgical lead at each clinical centre. Good Clinical Practice and local governance processes will be adhered to and monitored. Internal and independent steering and data monitoring committee meetings will be held regularly. Research ethics approval will be sought. The Bristol Randomised Trials Collaboration will oversee randomised trial conduct. Patient and Public Involvement The programme is underpinned by contributions from a patient forum, and will include patient-partners working on oversight groups, and involvement from Arthritis Care.

Lay abstract: Hip and knee replacement surgery is common, with over 145,000 operations in England and Wales in 2010. After surgery, about one person in a hundred develops a bacterial infection at their new, artificial joint. If untreated, infection of a replacement joint can result in severe pain, disability, and death. Costs to the NHS are substantial. Little is known about why some artificial joints become infected and what treatment is best. Treatment for infection of a replacement joint involves further expensive surgery. Our programme will deliver new knowledge and recommendations on the surgical management of such infections. When infection is found, there are two types of surgical treatment. One option is a 1-stage process, in which the artificial joint is removed, the area thoroughly cleaned of infected material and a new joint inserted immediately. The other option is a 2-stage process, in which the artificial joint is removed and replacement delayed for 3-6 months. Although a temporary &ldquo;spacer&rdquo; may be fitted, the patient has no joint until a replacement is inserted in a second operation. Both surgical treatments are widely used in conjunction with antibacterial chemotherapy. We do not know which is preferred by patients and which has the best long-term outcome. We will address these gaps in knowledge in 7 work packages (WP). These will be coordinated from the Avon Orthopaedic Centre and studies carried out in a collaboration between four tertiary referral centres. WP1. A thorough literature review will assess existing knowledge about causes of infection and the effectiveness of different treatments. WP2. Using information collected in the National Joint Registry we will identify reasons for infection and find out whether treatment (surgery plus antibiotics) is better at certain types of orthopaedic centre. WP3. Through interviews with patients and health professionals we will identify the impact on patients of infection and its treatment. This will advise us on how best to conduct a randomised controlled trial of the two available surgical treatments. WP4. We will then conduct a four centre randomised controlled trial, involving over 100 patients who have infection, and compare patient-centred outcomes after 1- and 2-stage surgical revision. WP5. Economic evaluation methods will assess value for money of treatments. WP6. We will explore individuals' preferences for the two surgical treatments. WP7. At the end of the programme we will inform stakeholders about good practice. We anticipate that our 5-year research programme will bring major benefits to patients and the NHS. We will produce knowledge about prediction, monitoring and how to treat infection after joint replacement. The programme will be conducted in collaboration with patient partners in a dedicated forum and we will deliver high quality evidence about best practice in the management of infection.

Research activity codes: 6.4 SURGERY
Health categories: MUSCULOSKELETAL;INFECTION