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Background: A deep infection of the surgical site is reported in 0.7% of all cases of total hip arthroplasty (THA). This often leads to revision surgery that is invasive, painful and costly. A range of strategies is employed in NHS hospitals to reduce risk, yet no economic analysis has been undertaken to compare the value for money of competing prevention strategies., Objectives: To compare the costs and health benefits of strategies that reduce the risk of deep infection following THA in NHS hospitals. To make recommendations to decision-makers about the cost-effectiveness of the alternatives., Design: The study comprised a systematic review and cost-effectiveness decision analysis., Setting: 77,321 patients who had a primary hip arthroplasty in NHS hospitals in 2012., Interventions: Nine different treatment strategies including antibiotic prophylaxis, antibiotic-impregnated cement and ventilation systems used in the operating theatre., Main Outcome Measures: Change in the number of deep infections, change in the total costs and change in the total health benefits in quality-adjusted life-years (QALYs)., Data Sources: Literature searches using MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Central Register of Controlled Trials were undertaken to cover the period 1966-2012 to identify infection prevention strategies. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. Orthopaedic surgeons and infection prevention experts were also consulted., Review Methods: English-language papers only. The selection of evidence was by two independent reviewers. Studies were included if they were interventions that reported THA-related deep surgical site infection (SSI) as an outcome. Mixed-treatment comparisons were made to produce estimates of the relative effects of competing infection control strategies., Results: Twelve studies, six randomised controlled trials and six observational studies, involving 123,788 total hip replacements (THRs) and nine infection control strategies, were identified. The quality of the evidence was judged against four categories developed by the National Institute for Health and Care Excellence Methods for Development of NICE Public Health Guidance ( http://publications.nice.org.uk/methods-for-the-development-of-nice-public-health-guidance-third-edition-pmg4 ), accessed March 2012. All evidence was found to fit the two highest categories of 1 and 2. Nine competing infection control interventions [treatments (Ts) 1-9] were used in a cohort simulation model of 77,321 patients who had a primary THR in 2012. Predictions were made for cases of deep infection and total costs, and QALY outcomes. Compared with a baseline of T1 (no systemic antibiotics, plain cement and conventional ventilation) all other treatment strategies reduced risk. T6 was the most effective (systemic antibiotics, antibiotic-impregnated cement and conventional ventilation) and prevented a further 1481 cases of deep infection, and led to the largest annual cost savings and the greatest gains to QALYs. The additional uses of laminar airflow and body exhaust suits indicate higher costs and worse health outcomes., Conclusions: T6 is an optimal strategy for reducing the risk of SSI following THA. The other strategies that are commonly used among NHS hospitals lead to higher cost and worse QALY outcomes. Policy-makers, therefore, have an opportunity to save resources and improve health outcomes. The effects of laminar air flow and body exhaust suits might be further studied if policy-makers are to consider disinvesting in these technologies., Limitations: A wide range of evidence sources was synthesised and there is large uncertainty in the conclusions., Funding: The National Institute for Health Research Health Technology Assessment programme and the Queensland Health Quality Improvement and Enhancement Programme (grant number 2008001769).