Objectives The aim of this study was to analyze the strength of risk factors related to endodontic flare-ups and rank them in order of their importance Materials and methods A systematic literature search of PubMed, Cochrane Central Register of Controlled Trials, Scopus, and ISI Web of Knowledge, and grey literature was conducted up to November 2019. One hundred ninety-eight publications were identified. Twelve records fulfilled the eligibility criteria, and eight significant risk factors for flare-up, namely, "Periapical lesion," "multiple-visit treatment," "preoperative pain," "necrotic teeth," "female gender," "retreatment," "percussion pain," and "analgesics," were selected to construct the simulation model. The final data pool was established by the integration of data of common risk factors in the included articles. Monte Carlo method was used to analyze of combined numerical data, for simulation of the risk factor impacts. Ten thousand iterations were generated in the simulation model. Results The results of the simulation revealed that the risk estimates of the factors had varying ranges of influence and probability on the flare-up risk. "Periapical lesion" was found to be the most sensitive risk factor, following by "preoperative pain" which was ranked the second place. The third-ranked risk factor was "multiple-visit treatment." The least sensitive risk factors for endodontic flare-up were "retreatment," "female gender," "necrotic teeth," and "analgesics." Conclusions The present study provides better comprehension on the importance of risk factors for flare-up based on their risk estimates. Clinical relevance A Monte Carlo simulation was adopted to identify the most influential risk factors for endodontic flare-up with a ranking, which can be used to provide meaningful predictions and further insights into clinicians' perception of flare-up risk.
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