title: A protocol for a systematic review of the diagnostic accuracy of blood markers, synovial fluid, and tissue testing in periprosthetic joint infections (PJI).
abstract: BACKGROUND
  Total joint replacement (TJR) procedures have been one of the most rewarding interventions for treating patients suffering from joint disease. However, developing a periprosthetic joint infection (PJI) is a serious complication that is associated with the highest burden of cost and reduction in patients' quality of life compared to other complications following TJRs. One of the main challenges facing clinicians who are treating PJIs is accurately diagnosing infection in a timely fashion. Multiple orthopedic associations have published clinical guidelines for diagnosing PJI which are based solely on consensus approaches, expert opinions, and narrative reviews. We believe that a higher quality of scientific rigor is necessary to establish a diagnostic guideline that represents current evidence more accurately and that identifies important knowledge gaps in PJI diagnosis. Therefore, we will conduct a systematic review on diagnostic performance of blood markers, synovial fluids, and tissue tests for diagnosing PJI.
  
  
  METHODS
  Electronic search strategies will be developed and tested by an experienced medical information specialist in consultation with the review team, and gray literature will be searched using the checklist from CADTH's Grey Matters Light. Two reviewers will independently screen the literature for inclusion using the prespecified eligibility criteria. Non-English language and animal-only studies will be excluded. Quality assessment and data extractions by reviewers will be verified, and disagreements will be resolved through consensus or third party adjudication. We will assess the quality of individual studies using the QUADAS-2 tool and use GRADE to summarize the strength of body of evidence. Analyses of evidence will be conducted in accordance with the Cochrane Handbook for Diagnostic Test Accuracy Reviews.
  
  
  CONCLUSIONS
  We will conduct a systemic review of tests (blood markers, synovial fluids, and tissue testing) for diagnosing PJI in patients' knee, hip, and shoulder joint replacements. This will be the first scientifically rigorous and comprehensive systematic review in the field and may feed into an evidence-based clinical practice guideline. We will compare the findings of this review with the consensus-based guides and discuss the differences, similarities, and knowledge gaps.
  
  
  BACKGROUND
  PROSPERO CRD42015023768.
authors.affiliation: Division of Orthopaedic Surgery, University of Ottawa, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. pbeaule@toh.on.ca.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Beaule
authors.affiliation: Knowledge Synthesis Group, Ottawa Hospital Research Institute, Center for Practice-Changing Research, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. bevshea35@gmail.com.
authors.forename: Beverley
authors.initials: B
authors.lastname: Shea
authors.affiliation: Division of Orthopaedic Surgery, University of Ottawa, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. habdelbary@toh.on.ca.
authors.forename: Hesham
authors.initials: H
authors.lastname: Abedlbary
authors.affiliation: Knowledge Synthesis Group, Ottawa Hospital Research Institute, Center for Practice-Changing Research, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. nahmadzai@ohri.ca.
authors.forename: Nadera
authors.initials: N
authors.lastname: Ahmadzai
authors.affiliation: Knowledge Synthesis Group, Ottawa Hospital Research Institute, Center for Practice-Changing Research, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. bskidmore@rogers.com.
authors.forename: Becky
authors.initials: B
authors.lastname: Skidmore
authors.affiliation: Ottawa Hospital Research Institute, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. rmallick@ohri.ca.
authors.forename: Ranjeeta
authors.initials: R
authors.lastname: Mallick
authors.affiliation: Knowledge Synthesis Group, Ottawa Hospital Research Institute, Center for Practice-Changing Research, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. bhiddy9999@gmail.com.
authors.forename: Brian
authors.initials: B
authors.lastname: Hutton
authors.affiliation: University of Ottawa Faculty of Medicine, 451 Smyth Rd., Ottawa, ON, K1H 8L1, Canada. alexandra.bunting@uottawa.ca.
authors.forename: Alexandra C
authors.initials: AC
authors.lastname: Bunting
authors.affiliation: Bruyère Research Institute, 85 Primrose Ave., Ottawa, ON, K1R 6M1, Canada. juliandeanmoran@gmail.com.
authors.forename: Julian
authors.initials: J
authors.lastname: Moran
authors.affiliation: Knowledge Synthesis Group, Ottawa Hospital Research Institute, Center for Practice-Changing Research, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. rward@ohri.ca.
authors.forename: Roxanne
authors.initials: R
authors.lastname: Ward
authors.affiliation: Knowledge Synthesis Group, Ottawa Hospital Research Institute, Center for Practice-Changing Research, 501 Smyth Rd., Ottawa, ON, K1H 8L6, Canada. dmoher@ohri.ca.|School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada. dmoher@ohri.ca.
authors.forename: David
authors.initials: D
authors.lastname: Moher
mesh_terms: D019643:Arthroplasty, Replacement / Q000009:adverse effects*; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism*; D042241:Early Diagnosis; D019317:Evidence-Based Medicine; D006801:Humans; D017410:Practice Guidelines as Topic; D016459:Prosthesis-Related Infections / Q000175:diagnosis*; D012107:Research Design; D013582:Synovial Fluid / Q000382:microbiology*; D013583:Synovial Membrane / Q000382:microbiology / Q000473:pathology*; D000078202:Systematic Reviews as Topic
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein