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Introduction: Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, the first in a 5-part series, outlines the methods for developing COS-ENDO, with detailed findings for each treatment presented in subsequent parts., Methods: Outcomes were identified through scoping reviews, a qualitative study with patients, and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO., Results: Of the 97 invited participants to Round 1, 77 (79%) registered, and 73 (95%) completed the survey, including 24 Academicians/Researchers, 26 Clinicians, and 23 Patients (or their caregivers/parents). They rated 64 outcomes, totaling 182 occurrences across treatments: 39 for Nonsurgical Root Canal Treatment/Retreatment, 46 for Surgical Endodontics, 46 for Vital Pulp Therapy, and 51 for Apexification/Regenerative Endodontics. The outcomes that achieved consensus for inclusion and those lacking consensus (either for inclusion or exclusion) advanced to Round 2 for re-rating by 70 participants. During the final consensus meeting, 16 participants discussed the outcomes and finalized the COS-ENDO., Conclusion: COS-ENDO is an important step toward standardizing outcome reporting in endodontics. Its implementation will ensure consistent reporting, enhancing research utility and evidence synthesis. Further efforts are needed to establish optimal measurement methods., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, Part 3 of a 5-part series, focuses on COS-ENDO for Surgical Endodontics, while other parts address the remaining treatments., Methods: Outcomes were identified through a scoping review, a qualitative study with patients, and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO., Results: Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients or their parents/caregivers) assessed 46 outcomes, with 17 excluded. The remaining outcomes-7 achieving consensus for inclusion and 22 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 1 outcome achieving consensus for exclusion, 10 for inclusion, and 18 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Surgical Endodontics, including Tooth survival, Pain, Signs of infection, Radiographic evidence of periradicular healing, Success, Functional tooth, Need for further intervention, and Adverse events/Complications., Conclusion: COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods., Competing Interests: Conflict of interest statement The authors and the steering committee members deny any conflict of interest related to this study. We affirm that we have no financial affiliation (e.g., employment, direct payment, stock holdings, retainers, consultantships, patent licensing arrangements or honoraria), or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past three years., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, Part 2 of a 5-part series, focuses on COS-ENDO for Nonsurgical Root Canal Treatment/Retreatment, while other parts address the remaining treatments., Methods: Outcomes were identified through scoping reviews, a qualitative study with patients, and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO., Results: Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients (or their parents/caregivers) assessed 39 outcomes, with 18 excluded. The remaining outcomes-7 achieving consensus for inclusion and 14 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 9 outcomes achieving consensus for inclusion, and 12 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Nonsurgical Root Canal Treatment/Retreatment, including Tooth survival, Pain, Signs of infection, Radiographic evidence of periradicular healing, Success, Functional tooth, Need for further intervention, and Adverse events/Complications., Conclusion: COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods., Competing Interests: Conflict of interest statement The authors and the steering committee members deny any conflict of interest related to this study. We affirm that we have no financial affiliation (e.g., employment, direct payment, stock holdings, retainers, consultantships, patent licensing arrangements or honoraria), or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past three years., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, the last in a 5-part series, focuses on COS-ENDO for Apexification and Regenerative Endodontics, while other parts address the remaining treatments., Methods: Outcomes were identified through scoping reviews and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO., Results: Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients or their parents/caregivers) assessed 51 outcomes, with 18 excluded. The remaining outcomes-7 achieving consensus for inclusion and 26 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 14 outcome achieving consensus for inclusion, and 19 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Apexification and Regenerative Endodontics, including Tooth survival, Pain, Signs of infection, Radiographic evidence of periradicular healing, Continued root development, Success, Functional tooth, Need for further intervention, and Adverse events/Complications., Conclusion: COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set for Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, Part 4 of a 5-part series, focuses on COS-ENDO for Vital Pulp Therapy, while other parts address the remaining treatments., Methods: Outcomes were identified through a scoping review and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO., Results: Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients or their parents/caregivers) assessed 46 outcomes, with 17 excluded. The remaining outcomes-4 achieving consensus for inclusion and 25 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 10 outcomes achieving consensus for inclusion, and 19 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Vital Pulp Therapy studies, including Tooth survival, Pain, Signs of infection, Radiographic evidence of maintained periradicular health, Continued root development, Success, Functional tooth, Need for further intervention, and Adverse events/Complications., Conclusion: COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods., Competing Interests: Conflict of interest statement The authors and the steering committee members deny any conflict of interest related to this study. We affirm that we have no financial affiliation (e.g., employment, direct payment, stock holdings, retainers, consultantships, patent licensing arrangements or honoraria), or involvement with any commercial organization with direct financial interest in the subject or materials discussed in this manuscript, nor have any such arrangements existed in the past three years., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to establish which anesthetic agents are associated with minimized adverse outcomes during laryngeal mask airway (LMA) insertion., Methods: Databases were searched for randomized controlled trials (RCTs) with American Society of Anesthesiologists I or II adult patients (≥15 years of age) receiving general anesthesia (GA) with an LMA. Propofol only was the comparator to other anesthetics used during LMA insertion. The primary outcome was prolonged apnea, and secondary outcomes were adverse airway events, LMA insertion failure, inadequate depth of anesthesia, and hemodynamic events. A network meta-analysis was conducted to estimate the treatment effects (odds ratios, 95% credible intervals, and surface under the cumulative ranking curve [SUCRA])., Results: A total of 28 anesthetic combinations used on 4695 patients for GA induction and LMA insertion were examined across 53 RCTs. Overall, there was an apnea incidence rate of 33.3% (849 of 2548) with a mean time of 3.74 ± 3.56 minutes (n = 3091). Propofol + dexmedetomidine had the highest overall summed score of SUCRA ranks in reducing adverse outcomes (apnea incidence: SUCRA = 37%, apnea time: SUCRA = 66%, airway adverse event: SUCRA = 67%, insertion failure: SUCRA = 73%, inadequate depth of anesthesia: SUCRA = 84%). In comparison among all propofol combinations, propofol alone ranked lowest for overall summed score of SUCRA in reducing adverse outcomes (apnea incidence: SUCRA = 47%, apnea time: SUCRA = 71%, airway adverse event: SUCRA = 9%, insertion failure: SUCRA = 20%, inadequate depth of anesthesia: SUCRA = 9%)., Conclusion: All anesthetic combinations, other than those with thiopental, reduced adverse outcomes as compared with propofol alone. The combination of propofol and dexmedetomidine infused over 10 minutes ranked as the most effective for reducing adverse outcomes during LMA insertion.

Article Title and Bibliographic Information: Wang Y, Chen CY, Stathopoulou PG, Graham LK, Korostoff J, Chen YW. Efficacy of Antibiotics Used as an Adjunct in the Treatment of Peri-implant Mucositis and Peri-implantitis: A Systematic Review and Meta-analysis. Int J Oral Maxillofac Implants. 2022 Mar-Apr;37(2):235-249. doi:10.11607/jomi.9220. PMID: 35476853., Source of Funding: None., Type of Study/design: Systematic review with meta-analysis of data., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: The aim of this study was to assess which treatment modality regarding scaffold selection for immature permanent teeth with pulpal necrosis will be the most successful for regenerative endodontic treatment (RET)., Methodology: PubMed, Cochrane, Web of Science and Embase, and additional records until August 2022 were searched providing a total of 3021 articles, and nine of these articles were included for quantitative synthesis. The reviewers selected eligible randomized controlled trials and extracted pertinent data. Network meta-analysis was conducted to estimate treatment effects for primary outcomes (clinical and radiographic healing) and secondary outcomes (apical closure, root length and root wall thickness increase) following RET [mean difference (MD); 95% credible interval (CrI) and surface under the cumulative ranking curve (SUCRA)]. The quality of the included studies was appraised by the revised Cochrane risk of bias tool, and the quality of evidence was assessed using the GRADE approach., Results: Six interventions from nine included studies were identified: blood clot scaffold (BC), blood clot scaffold with basic fibroblast growth factor, blood clot scaffold with collagen, platelet pellet, platelet-rich plasma (PRP) and platelet-rich fibrin (PRF). The PRP scaffold showed the greatest increase in root lengthening at 6-12 months (MD = 4.2; 95% CrI, 1.2 to 6.8; SUCRA = 89.0%, very low confidence). PRP or PRF achieved the highest level of success for primary and secondary outcomes at 1-6 and 6-12 months. Blood clot scaffold (with collagen or combined with basic fibroblast growth factor (bFGF)) achieved the highest level of success for secondary outcomes beyond 12 months follow-up. A very low to low quality of evidence suggests that both PRP and PRF exhibit the greatest success evaluating primary and secondary outcomes within 12 months postoperatively compared to the traditional blood clot scaffold protocol., Conclusion: Limited evidence suggests both PRP and PRF exhibit success in the short-term, not long-term. The value of this information stems in its recommendation for future randomized trials prioritizing both of these materials in their protocol., (© 2023 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Introduction: There is considerable variation in the reporting of treatment outcomes in endodontics. Patient-centered outcomes are often inadequately reported in endodontic outcome studies. This paper explores patients' expectations and reported outcomes in nonsurgical root canal treatment (NS-RCT), nonsurgical root canal retreatment (NS-ReTx), and endodontic microsurgery (EMS)., Methods: We used a qualitative description approach and conducted telephone and virtual semi-structured interviews with participants who had the following treatments within the preceding 3-12 months: NS-RCT (n = 10), NS-ReTx (n = 10), or EMS (n = 10). Half of these treatments were performed by senior endodontic residents in an academic setting and the other half by a community-based endodontist at a private practice., Results: Participants identified several outcomes that were important to them and integral to treatment success, such as tooth survival, resolution of symptoms, aesthetics, and radiographic healing. Process-related factors were as important as treatment outcomes for participants. Communicating with and educating patients during treatment increased participants' satisfaction and lowered their stress. Dissatisfaction was linked to the lack of a comprehensive treatment and follow-up plan. Thorough planning ensured that patients were fully informed and had a structured approach to achieving their desired outcomes., Conclusions: This study provides a list of outcomes that are important for patients undergoing NS-RCT, NS-ReTx, and EMS. These outcomes should be considered when developing a core outcome set related to endodontic treatments. Additionally, this study reports patients' expectations regarding process-related factors that are essential for providing patient-centered care and improving patient experience., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Serious airway complications can occur with inadequate airway management during general anesthesia (GA). This meta-analysis investigated randomized controlled trials that compared perioperative technique failures and airway complications, including hypoxia, during GA for dentistry using endotracheal intubation or a laryngeal mask airway (LMA) for airway management., Methods: A systematic search of electronic databases and gray literature was completed. Independent reviewers assessed eligibility, performed data extraction, completed risk of bias assessment, and judged the quality of results through Grading of Recommendations, Assessment, Development, and Evaluation. Risk ratios (RRs) for airway complications, with 95% CIs, were calculated. Heterogeneity was quantified using the I2 statistic. Sensitivity and age-subgroup analyses were explored., Results: Six trials were deemed eligible from a total of 9076 identified reports. The airway management intervention for these trials was LMA. Technique failures or effect differences in airway complications were not detected except for postoperative hypoxia, where LMA use had a decreased risk (RR, 0.22; 95% CI, 0.06-0.77; I2 = 0%; moderate quality). A similar effect was seen in the pediatric analysis (RR, 0.10; 95% CI, 0.01-0.84; I2 = 0%; moderate quality). Additionally, LMA use reduced pediatric sore throat risk (RR, 0.08; 95% CI, 0.04-0.15; I2 = 0%; moderate quality)., Conclusion: Use of an LMA in dentistry may have the potential to reduce the risk of postoperative hypoxia, particularly in pediatric patients, although further study is required., (© 2021 by the American Dental Society of Anesthesiology.)

Decreasing orthodontic treatment duration is at the forefront of innovation for clinical orthodontics. This network meta-analysis aimed to determine the relative efficacy and safety of treatments for accelerated orthodontic tooth movement (OTM) in patients undergoing extraction of maxillary first premolars followed by canine retraction in any orthodontic setting. MEDLINE, EMBASE, Cochrane CENTRAL, CINAHL and SCOPUS were searched (from inception to 20 April 2020). Study selection and data extraction were performed in duplicate. Eligible randomized controlled trials (RCTs) were meta-analysed to estimate the rate of tooth movement, 95% credible interval and surface under the cumulative ranking curve (SUCRA) in the first 3 months following the application of the adjunctive accelerative method. Eligible RCTs were assessed by Cochrane risk of bias tool, and quality of evidence was assessed by GRADE approach, obtained from CINeMA web application. Interventions were ranked for efficacy and reviewed for safety. Nineteen studies pertaining to eight interventions, with data from 415 patients were included. Quality of evidence was very low to moderate. Very low-to low-quality evidence suggests that corticotomy is an efficacious and safe adjunctive treatment to accelerate OTM in comparison with conventional treatment in the first 2 months of treatment. Low-quality evidence suggests that piezocision and micro-osteoperforations (MOP) are efficacious and safe adjunctive treatments only in the first month of treatment. Frequent MOP in conjunction with low-level laser therapy appeared to be an efficacious and safe adjunctive treatment only in the first month following its initial application but not thereafter., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The purpose of this study was to evaluate the efficacy and safety of postoperative medications in decreasing pain after nonsurgical endodontic treatment using a network meta-analytic approach., Methods: MEDLINE, Embase, CENTRAL, CINAHL, and Scopus were searched (until July 31, 2019). Two reviewers selected eligible randomized controlled trials and extracted and meta-analyzed data to estimate the treatment effects of pain assessed on a 0-100 scale (mean difference [MD]); 95% credible interval [CrI], and surface under the cumulative ranking curve [SUCRA]) at 6-8, 12, 24, and 48 hours postoperatively after the administration of various interventions. The Cochrane risk of bias tool was applied to eligible trials. The overall quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach obtained from the CINeMA Web application (University of Bern, Bern, Switzerland)., Results: Eight interventions among 11 studies were identified: nonsteroidal anti-inflammatory drugs (NSAIDs), NSAIDs + acetaminophen, NSAIDs + benzodiazepines, NSAIDs + opioids, corticosteroids, opioids, acetaminophen, and placebo. Compared with placebo, nonsurgical endodontic treatment pain 6-8 hours postoperatively improved with NSAIDs + acetaminophen (MD = -22; 95% CrI, -38 to -7.2; SUCRA = 73%; moderate confidence) and NSAIDs (MD = -21; 95% CrI, -34 to -7.6; SUCRA = 68%; very low confidence). At 12 and 24 hours, only NSAIDs were effective in decreasing postoperative pain. At 48 hours, no treatment resulted in significant pain reduction. Corticosteroids and opioids did not significantly decrease pain. No major safety concerns were reported., Conclusions: Very low- to moderate-quality evidence suggests that NSAIDs or NSAIDs + acetaminophen administered after nonsurgical endodontic treatment lead to a clinically relevant decrease in postoperative pain for patients with irreversible pulpitis or pulpal necrosis and are the most effective treatments available. Postoperative corticosteroids or opioids did not significantly decrease postoperative pain., (Copyright © 2020 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Article Title and Bibliographic Information: Evidence-based clinical practice guideline on antibiotic use for the urgent management of pulpal- and periapical-related dental pain and intraoral swelling: A report from the American Dental Association. Lockhart PB, Tampi MP, Abt E, et al. J Am Dent Assoc 2019;150(11):906-921.e12., Source of Funding: The American Dental Association., Type of Study/design: Systematic review with meta-analysis of data., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The aims of this study were to investigate if Toll-like receptor 4 (TLR4) is expressed in the medullary dorsal horn (MDH) and if medullary application of a TLR4 antagonist (lipopolysaccharides from Rhodobacter sphaeroides , LPS-RS) can attenuate changes in nociceptive sensorimotor responses or TLR4 expression that might be evoked by mustard oil (MO) application to the right maxillary first molar tooth pulp. Of 41 adult male Sprague-Dawley rats used in the study, 23 received intrathecal application of the TLR4 antagonist LPS-RS (25 μg/10 μl; LPS-RS group) or isotonic saline (10 μl; vehicle control group) 10 min before pulpal application of MO (95%; 0.2 μl). Bilateral electromyographic (EMG) activities of the anterior digastric and masseter muscles were recorded continuously before and until 15 min after the MO application to the pulp. In 6 of these 23 rats and an additional 18 rats, the caudal medulla containing the ipsilateral and contralateral MDH was removed after euthanasia for subsequent Western Blot analysis of TLR4 expression in LPS-RS ( n = 8) and vehicle ( n = 8) groups and a naïve group ( n = 8). The % change from baseline in the MO-evoked EMG activities within the anterior digastric muscles were significantly smaller in the LPS-RS group than the control group (two-way ANOVA, post hoc Bonferroni, P < 0.0001). Western Blot analysis revealed similar levels of TLR4 expression in the caudal medulla of the naïve, vehicle and LPS-RS groups. These novel findings suggest that TLR4 signaling in the caudal medulla may mediate MO-induced acute dental inflammatory pain in rats., (Copyright © 2020 Filippini, Molska, Zanjir, Arudchelvan, Gong, Campos, Avivi-Arber and Sessle.)

Article Title and Bibliographic Information: Effect of preoperative corticosteroids in patients with symptomatic pulpitis on postoperative pain after single-visit root canal treatment: a systematic review and meta-analysis. Suneelkumar C, Subha A, Gogala D. J Endod 2018; 44(9):1347-54., Source of Funding: Not provided., Type of Study/design: Systematic review with meta-analysis of data., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Several strategies have been investigated for achieving successful pulpal anesthesia during endodontic treatment of mandibular molars with symptomatic irreversible pulpitis. However, comprehensive evaluation and identification of the most efficacious and safe intervention are lacking. We aimed to determine this using network meta-analysis., Methods: MEDLINE, Embase, Cochrane Central, CINAHL, and Scopus databases were searched. Study selection and data extraction were performed in duplicate. Eligible randomized controlled trials were meta-analyzed to estimate the treatment effects (odd ratios [ORs]; 95% credible interval (CrI) and surface under the cumulative ranking curve (SUCRA)]. CINeMA software (University of Bern, Bern, Switzerland) was used to assess the quality of results., Results: Thirty-seven interventions from 46 studies were identified. Compared with the common practice of an inferior alveolar nerve block with 2% lidocaine, a supplemental intraosseous injection was ranked the most efficacious with very low to moderate confidence (2% lidocaine + preoperative nonsteroidal anti-inflammatory drugs [NSAIDs] + acetaminophen [OR = 74; 95% CrI, 15-470; SUCRA = 97%], 2% lidocaine + preoperative NSAIDs [OR = 46; 95% CrI, 8-420; SUCRA = 94%], 2% lidocaine [OR = 33; 95% CrI, 14-80; SUCRA = 93%], 2% lidocaine + preoperative opioids + acetaminophen [OR = 20; 95% CrI, 4.4-98; SUCRA = 86%], and 4% articaine [OR = 20; 95% CrI, 6.3-96; SUCRA = 87%]) followed by supplemental buccal and lingual infiltrations using 4% articaine + preoperative NSAIDs (OR = 18; 95% CrI, 6-56; SUCRA = 86%; very low confidence). No major safety concerns were reported., Conclusions: Very low- to moderate-quality evidence suggests intraosseous injection using 2% lidocaine with 1:100,000 epinephrine or 4% articaine with 1:100,000 epinephrine or buccal and lingual infiltrations of 4% articaine with 1:100,000 epinephrine are superior strategies to achieve pulpal anesthesia during endodontic treatment of mandibular molars with symptomatic irreversible pulpitis. Preoperative NSAIDs or opioids with or without acetaminophen may increase the efficacy of these injections., (Copyright © 2019 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)