1. What is the SynovasureTM Test?
  2. Synovasure is a Lab Developed Test (LDT) which uses synovial fluid for the diagnosis of Periprosthetic Joint Infection (PJI). The Synovasure test includes three measurements: (1) an immunoassay measurement of synovial fluid alpha defensin, (2) an immunoassay measurement of synovial fluid CRP and (3) a measurement of synovial fluid hemoglobin.

  3. Why is the synovial fluid alpha defensin level measured as part of the Synovasure Test?
  4. Synovial fluid alpha defensin level is highly accurate in diagnosing periprosthetic joint infection. The sensitivity of synovial fluid alpha defensin for PJI is 97% and the specificity of synovial fluid alpha defensin for PJI is 96%.

  5. Why is the synovial fluid CRP level measured as part of the Synovasure Test?
  6. The false positive rate associated with synovial fluid alpha defensin is 4%. In our studies, we found that these false positive alpha defensin samples could frequently be identified by their concurrently low synovial fluid CRP value (<3mg/L). Therefore, when the scenario of a high alpha defensin and a low CRP in the synovial fluid occurs, we report an accompanying warning that the Synovasure result could potentially be a false positive. For these cases, we recommend that the physician seriously consider all clinical information for diagnosis.

  7. Why is the synovial fluid hemoglobin level measured as part of the Synovasure Test?
  8. The synovial fluid hemoglobin level is measured as part of the Synovasure Test to quantify the level of lysed blood cells that may have resulted from sample acquisition and shipment. This synovial fluid hemoglobin level is used to adjust the diagnostic threshold of the Synovasure Test. When there is excessive blood cell lysis present, the result is reported as invalid.

  9. Can Synovasure be used to diagnose infection in a native joint?
  10. Synovasure PJI was not developed for diagnosing native septic arthritis, and has not been validated for native synovial fluid samples. Preliminary data demonstrates that the Synovasure PJI Test does not provide accuracy when diagnosing native septic arthritis. A diagnostic test for native infection is under development and will be released in the near future.

  11. How does Synovasure compare with the Leukocyte Esterase test?
  12. In our studies, Synovasure has outperformed the LE test strip in both accuracy and the ability to provide valid results. Our data and other studies have shown that the sensitivity of the LE test strip is approximately 80%. The leukocyte esterase test strip also yields a high proportion of unreadable samples due to blood contamination in the synovial fluid (up to 30%).

  13. Can Synovasure be used prior to reimplantation to confirm absence of infection?
  14. Synovasure PJI's indication for use is for the assessment of an arthroplasty prior to revision. At this time there are studies underway to assess the accuracy of Synovasure PJI in the setting of a reimplantation.

  15. Can Synovasure be used on a saline-wash sample?
  16. Saline washing is not approved as a collection method for Synovasure as this will dilute the protein levels in the synovial fluid.

  17. How do I interpret the Synovasure results if a patient has been on antibiotics?
  18. In the 158 patient study described in the Synovasure white paper, 27% of infected patients had been treated with antibiotics prior to aspiration. All of these patients had a positive Synovasure test, and the mean alpha defensin level was not different when comparing infected patients being treated with antibiotics versus those not on an antibiotic program.

  19. How was the performance of the Synovasure product determined?
  20. Several studies have evaluated the performance of Synovasure, using the MSIS definition of infection as the "gold standard".

  21. How do I get the results from Citrano/CD Diagnostics?
  22. After the test is completed, results can be sent via email or fax, or they can be accessed online.

  23. What results do I get back from CD and how do I use this information in the treatment of a patient?
  24. Synovasure results are intended to be used in conjunction with other clinical and diagnostic findings to aid a patient's diagnosis. Synovasure is intended to determine whether there is an infection present in the synovial fluid at a joint arthroplasty. It is not intended to identify a specific type of infection or establish the origin or severity of an infection. It is intended to provide a physician with a specific positive or negative result for the presence of the alpha-defensin biomarker that is released into the synovial fluid by the patient's cells while fighting an infection.

  25. How does Synovasure perform in the setting of inflammatory arthritis?
  26. Our studies evaluating the performance of Synovasure included patients with inflammatory conditions. In the 158 patient study described in the Synovasure white paper, 23% of patients had a concurrent diagnosis of an inflammatory condition. This population of patients did not affect the performance of the Synovasure. test, nor were the alpha-defensin levels significantly different in this population.

  27. What is Synovasure's turnaround time? If the test is positive for an infection will the test determine what the organism is?
  28. Synovasure provides a positive or negative result for alpha defensin. Standard culture methods are available at Citrano Laboratories for the identification of the organism. The initial Synovasure result will be reported within 24 hours of sample receipt, but the culture results (if requested) will be reported as "pending" until the test is complete. Culture negative results are reported after they are negative for the full culture period.

  29. The sender information is not on the FedEx shipping package. How can we track this?
  30. The physician's office can track the shipment using the tracking number on the FedEx return label (or photocopy the label) on the pouch provided.

  31. Is there a cutoff time for Fed Ex package pick up?
  32. There are specific instructions on the Test Submission Document (from CD Diagnostic's website) to insure that the samples are picked up and delivered in a timely fashion. To schedule your "prepaid pickup".
    Call 1-800-463-3339 (1-800-GOFEDEX) or schedule online through www.fedex.com.
    Note: packages CANNOT be placed in a FedEx dropbox.

  33. How do I get started?
  34. Fill out the Synovasure Enrollment document and fax to CD Diagnostics. Once received, you will be sent kit to have on hand in your office. Next, ask your Zimmer rep to familiarize your staff with the paperwork and submission process. Finally make sure you always have 2-3 Synovasure kits readily accessible in your practice or satellite office. Need more kits... order them from CD Diagnostics. Once you are shipping samples routinely, you will receive kits by auto replenishment.

  35. What is in a Synovasure kit?
  36. The Synovasure kit contains the materials needed to send synovial fluid to CD Diagnostics/Citrano Labs; sample tubes, test requisition/insurance form, leak-proof bag, mailing box and prepaid FedEx envelope. Once you have a sample ready to be sent, have your staff call FedEx for an overnight "prepaid pick-up".

  37. How do I treat a sample if I see the patient on a Friday?
  38. If you aspirate a synovial fluid sample on Friday or after Fed EX pickup, you can hold the sample in a refrigerator for up to 3 days prior to shipping.

  39. How much does the test cost?
  40. The list price for the Synovasure Panel is $93.00. If you opt to have cultures done in addition to Synovasure, the cost is an additional $25 for aerobic and $25 for anaerobic cultures, with additional charges for bacterial identification and antibiotic sensitivity (these differ based on the organism (bacteria vs. fungus) and number of organisms grown in culture).

  41. How is the patient billed and what if the insurance does not pay?
  42. When you submit a sample, you will also complete a Requisition Form. This document accompanies the sample to the lab and the patient billing information must be included on this form. CD Diagnostics/Citrano Labs will bill the patient's insurance. If the insurance declines coverage, the patient is responsible to cover the cost.

  43. What is the billing process?
  44. When you aspirate a sample, you will continue to charge for aspiration as usual, and CD Diagnostics/Citrano Labs will bill the patient's insurance for the tests you select on the Requisition form (Synovasure / Culture). In cases in which the arthrocentesis is being billed by the hospital, the hospital is required to bill Medicare for the Synovasure test. Citrano Laboratories is required to charge the hospital for the services performed and the hospital will be paid pursuant to Medicare policies that guide reimbursement for inpatient or outpatient services. A discount will be provided to hospital laboratories that bill Synovasure tests directly.

  45. What is the investment to have kits available in your practice?
  46. There is no "out of pocket" cost to surgeon or practice.

  47. Are insurance companies paying for the test?
  48. Most claims are reimbursed by insurance companies, at various rates. Occasionally insurance will not pay due to network requirements or the patient's deductible. CD Diagnostics accepts the insurance's contractual adjustments and does not balance bill the physician or the patient.

  49. Where is the testing done?
  50. Synovasure LDT is exclusively serviced by Citrano Medical Laboratories, a subsidiary of CD Diagnostics results are determined and returned to the clinician within 24 hours of receipt. Citrano Medical Laboratories (CLIA License# 21D0216863) is based in Baltimore, MD.

Zimmer has exclusive distribution rights For SynovasureTM, Contact your Zimmer Rep, or CD Diagnostics for more information.