Prioritizing Research Informing Antibiotic Prophylaxis Guidelines for Knee Arthroplasty Patients.

INTRODUCTION: Guidelines for routine antibiotic prophylaxis (AP) before dental procedures to prevent periprosthetic joint infection (PJI) have been hampered by the lack of prospective clinical trials. OBJECTIVES: To apply value-of-information (VOI) analysis to quantify the value of conducting further clinical research to reduce decision uncertainty regarding the cost-effectiveness of AP strategies for dental patients undergoing total knee arthroplasty (TKA). METHODS: An updated decision model and probabilistic sensitivity analysis (PSA) evaluated the cost-effectiveness of AP and decision uncertainty for 3 AP strategies: no AP, 2-y AP, and lifetime AP. VOI analyses estimated the value and cost of conducting a randomized controlled trial (RCT) or observational study. We used a linear regression meta-modeling approach to calculate the population expected value of partial perfect information and a Gaussian approximation to calculate population expected value of sample information, and we subtracted the cost for research to obtain the expected net benefit of sampling (ENBS). We determined the optimal trial sample sizes that maximized ENBS. RESULTS: Using a willingness-to-pay threshold of $100,000 per quality-adjusted life-year, the PSA found that a no-AP strategy had the highest expected net benefit, with a 60% probability of being cost-effective, and 2-y AP had a 37% probability. The optimal sample size for an RCT to determine AP efficacy and dental-related PJI risk would require approximately 421 patients per arm with an estimated cost of $14.7 million. The optimal sample size for an observational study to inform quality-of-life parameters would require 2,211 patients with an estimated cost of $1.2 million. The 2 trial designs had an ENBS of approximately $25 to $26 million. CONCLUSION: Given the uncertainties associated with AP guidelines for dental patients after TKA, we conclude there is value in conducting further research to inform the risk of PJI, effectiveness of AP, and quality-of-life values. KNOWLEDGE TRANSFER STATEMENT: The results of this value-of-information analysis demonstrate that there is substantial uncertainty around clinical, health status, and economic parameters that may influence the antibiotic prophylaxis guidance for dental patients with total knee arthroplasty. The analysis supports the contention that conducting additional clinical research to reduce decision uncertainty is worth pursuing and will inform the antibiotic prophylaxis debate for clinicians and dental patients with prosthetic joints.

Is Antibiotic Prophylaxis Cost-effective for Dental Patients Following Total Knee Arthroplasty?

INTRODUCTION: Routine antibiotic prophylaxis (AP) to prevent prosthetic joint infection remains controversial. The lack of prophylaxis guideline consensus from the American Academy of Orthopaedic Surgeons (AAOS) and the American Dental Association (ADA) contributes to clinician confusion. OBJECTIVES: This cost-effectiveness decision model informs the AP debate and guideline development by comparing the benefits, harms, and costs of alternative prophylaxis strategies. METHODS: A Markov state-transition model was developed comparing lifetime health outcomes and costs of alternative AP strategies for dental patients aged 65 y with a history of total knee arthroplasty (TKA). Based on our interpretation of AP recommendations from the AAOS and ADA, incremental cost-effectiveness ratios were calculated to compare the following strategies: no AP, AP for the first 2 y after a TKA, and lifetime AP. RESULTS: The no-AP strategy had the lowest average lifetime costs ($17,119) and quality-adjusted life years (11.2151). Compared with a no-prophylaxis strategy, the 2-y AP strategy had incremental costs of $56 and 0.0006 QALYs gained and was cost-effective (incremental cost-effectiveness ratio = $95,100) when a willingness-to-pay threshold of $100,000 per quality-adjusted life year was used. Based on the results of 1-way sensitivity analysis, the no-AP strategy was cost-effective when we modestly increased base case amoxicillin adverse event estimates that were substantially lower than estimates reported in previous models. When plausible combinations of important model parameters were varied, model results suggested that there may be clinical scenarios when AP may be appropriate for some medically at-risk patient populations. CONCLUSION: The results of cost-effectiveness decision modeling generally support questioning routine AP for dental patients with TKA. Sensitivity analyses suggest that prophylaxis may be cost-effective for patient populations with a higher medical risk of infection. This finding is consistent with the recommendations of the 2015 ADA practice guideline and the appropriate use criteria jointly developed by the AAOS and the ADA. KNOWLEDGE TRANSFER STATEMENT: The results of this decision modeling research support the contention that routine AP before invasive dental procedures to prevent prosthetic joint infection may not be cost-effective for patients without medical conditions, potentially conferring a higher infection risk. Model sensitivity analyses suggest that there may be clinical situations when medically at-risk patients benefit from AP.

A follow-up case report of Actinobacillus actinomycetemcomitans in human periodontal disease.

The purpose of this investigation was to compare clinical and microbial parameters in a follow-up case report of adult subjects harboring Actinobacillus actinomycetemcomitans (Aa) with clinically matched subjects who did not have detectable Aa. 16 subjects with Aa and 16 subjects without Aa at the baseline examination were re-examined at an average of 46 months following collection of baseline data. Clinical measurements were recorded and subgingival plaque sampled and evaluated for microbial flora from each maxillary first molar. In 16 subjects with Aa at baseline, 4 sites in 3 subjects had detectable actinobacilli at the follow-up appointment. 26 sites in 13 individuals with Aa at baseline had a significantly increased gingival index at the follow-up visit (p less than or equal to 0.05), but there was no significant increase in probing depth or attachment loss. 32 sites in the 16 subjects without Aa at baseline still did not have detectable levels of this microorganism at the follow-up examination nor was there any significant difference between baseline and the follow-up appointment for the gingival index, probing depth and attachment level measurements. In subjects with Aa at baseline, 1 of 12 teeth without Aa and 5 of 20 teeth with Aa had been extracted prior to the follow-up visit. In this population group, having sites where Aa was detected, 6 of 9 teeth which had a probing depth greater than or equal to 5 mm were lost before the follow-up data collection appointment. In the control group, which did not have detectable Aa at baseline, 9 teeth with probing depths greater than or equal to 5 mm were not lost. These observations, although not proving, suggest in this population group, that deeper probing depths taken together with the presence of Aa may have placed an individual at greater risk of tooth loss.