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Data sources A comprehensive collection of databases were searched from inception to August 2020, such as Cochrane, MEDLINE, Scopus and Web of science. Also, references and citations of retrieved records, conference proceedings and leading journals were searched. Study selection All randomised clinical trials on root-canal-treated adult permanent teeth that compared the outcomes of ultrasonically activated irrigation (UAI) to syringe irrigation (SI) were eligible. The outcomes considered were post-operative pain, pain intensity, periapical healing after 12 months, the incidence of microbial presence, microbial quantification, lipopolysaccharides (LPS) quantification and lipoteichoic acid quantification. Studies with insufficient data for risk of bias assessment or other outcomes were excluded. Data extraction and synthesis The two independent reviewers did the screening process in title, abstract and full-text assessment steps. Also, the data extraction process and risk of bias assessment were done by two independent reviewers. Any disagreement was resolved by consensus or the opinion of a third reviewer. Any missing information was filled in by contacting the authors. The Cochrane risk-of-bias tool for randomised trials was used to assess the risk of bias. The following domains were evaluated for risk of bias: randomisation process, deviation from the intended interventions, missing outcome data, outcome measurement and the selection of the reported results. If all domains were rated as 'low risk', judgements would be rated as 'low risk', otherwise, 'high risk'. The risk ratios and mean risk difference with 95% confidence interval (CI) were used as measure effect. The random effects model was used to combine the effects. The heterogeneity is measured by I2 test (I2 test >50% and p <0.1 considered as substantial heterogeneity). The level of certainty of evidence for clinically important outcomes was determined using the guidelines of Grading of Recommendations Assessment, Development and Evaluation working group. Results Four studies entered the meta-analysis stage based on pain outcomes. The overall risk of bias for three of them was assessed as high. All of them had examined pain incidence before 24 hours but only two studies have examined the occurrence of pain in the period of 24-72 hours and after 72 hours to 7 days. Considerable heterogeny was among the incidence of pain <24 hours between studies (I2= 83%). Therefore, the incidence of pain in two sub-groups of vital and non-vital pulp has been investigated. In the non-vital pulps, the incidence of pain by UAI was half of the incidence of SI pain (relative risk= 0.50; 95% CI 0.35-0.71; I2 = 0%; 308 teeth). But no significant difference was seen in vital pulps. Also, there was no significant difference in the occurrence of pain after 72 hours between the two methods. Two studies assessed the intensity of pain in three periods: <24 hours, 72-24 hours, more than 72 hours and less than 7 days. The combined results based on vital and non-vital groups resulted in no significant difference in any period. Pooled data of pain outcomes were assessed with very low or low confidence of evidence. Five studies with microbiology-related outcomes entered the final analysis stage. The overall risk of bias for two of them was high. Three studies evaluated the effect of the irrigation method on microbial presence as an outcome. High heterogeneity was among the results of the studies (I2= 72%). However, with and without subgroup analysis, meta-analysis results showed no significant difference between these two methods. A lower microbial count was found with UAI than SI in a meta-analysis of four studies (standardised mean difference-pooled - 0.40; 95% CI [-0.78, -0.02]; I2 = 0%; 126 teeth). Two studies measured LPs. The meta-analysis showed lower values of LPS with UAI compared to SI (34, 37) (mean difference pooled - 0.06; 95% CI [-0.11, -0.01]; 61 root canals; I2 = 29%). One study measured lipoteichoic acid and found no significant difference between the irrigation methods. Three studies with treatment-success-related outcomes entered the meta-analysis stage with an overall high risk of bias. Two studies' pooled data revealed no significant difference between the irrigation methods regarding treatment failure. One study assessed periapical-lesion volume after treatment and found no significant difference between the irrigation methods. Conclusions According to limited data, UAI may reduce the risk of post-operative pain during the first 24 hours and reduce microbial counts, particularly cultivable germs in cases of apical periodontitis. However, most meta-analyses are conducted on a small number of studies and have an overall 'very low' to 'low' certainty of evidence; as a result, the evidence is deemed insufficient to either support or disprove UAI efficacy when compared to SI. [ABSTRACT FROM AUTHOR]

Data sources Medline, Embase, CENTRAL, Cumulative Index to Nursing and Allied Health Literature and Scopus databases were searched (until July 31 2019). They searched the WHO International Clinical Trials Registry Platform and ClinicalTrials.gov databases for completed and ongoing trials, as well as ProQuest, Google Scholar (first 100 hits) and the OpenGrey database for those unpublished. In addition, abstracts of annual meetings from the American Association of Endodontists, the International Federation of Endodontic Associations and the European Society of Endodontics were searched. A manual search of references in related papers and textbooks was carried out. Any missing information was filled in by contacting the authors. Study selection All randomised clinical trials (RCT) of nonsurgical endodontic therapy with pharmaceutical treatments provided postoperatively to alleviate pain on adult subjects were eligible. Two reviewers selected the studies and extracted the data and the results were examined by a third reviewer. Any differences were settled with the help of a fourth reviewer. Data extraction and synthesis Two authors independently evaluated and retrieved data from chosen trials found through searches. Another reviewer looked at the trial selection and data extraction. They also assessed the risk of bias in each of the research they chose. The mean and standard deviation of a 0-100 (mm) visual analogue pain scale were extracted or derived from study text, graphs and tables The postoperative medications were compared using network meta-analysis in a Bayesian model. Mean differences (MDs) and 95% credible intervals (CrIs) of post-operative pain were estimated at 6-8 hours and 12, 24 and 48 hours. Two authors utilised the CINeMA web application to assess the confidence in the main results by accounting for six domains: within- and across-study bias; indirectness; imprecision; heterogeneity; and incoherence. Each domain was assigned no concerns, major concerns, or minor concerns. Each result would be assigned a confidence level of high, moderate, low, or very low. To establish an agreement, a third reviewer was consulted. Results From the initial search of 969 records, 11 RCTs matched the inclusion criteria. Five studies were rated as having a low risk of bias, five as having a moderate risk and one as having a high risk. Moderate and major heterogeneity and some inconsistencies were detected, though not statistically significant. Oral medications were classified into placebo, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, acetaminophen, NSAIDs + acetaminophen, corticosteroids, NSAIDs + benzodiazepines and NSAIDs + opioids groups. With moderate confidence, NSAIDs + acetaminophen were shown to be more efficacious than placebo at 6-8 hours following nonsurgical root canal therapy (MD = 22; 95% CrI = [-38, -7.2]). With very low confidence, NSAIDs had a greater effect than placebo after 12 and 24 hours (MD = -28; 95% CrI = [-49, -7] and MD = -15; 95% CrI = [-27, -2.3], respectively). After 6 12 and 24 hours, other medications were no more effective than placebo in pain reduction. After 48 hours, no treatment was more effective than placebo. Subgroup analysis found that other medications, such as corticosteroids and acetaminophen, were no more beneficial than placebo for patients who could not use NSAIDs. Six trials provided safety data and concluded that the therapies were safe and posed no significant risks. Conclusions Very low to moderate-quality evidence suggests that postoperative administration of NSAIDs and acetaminophen, or NSAIDs alone, reduced discomfort after non-surgical root canal therapy in patients with irreversible pulpitis or pulpal necrosis. Trials have shown, however, that using these drugs does not result in major complications. We cannot, however, be confident that they are risk-free. [ABSTRACT FROM AUTHOR]