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  1. Nagendrababu V, Duncan HF, Fouad AF, Kirkevang LL, Parashos P, Pigg M, et al.
    Int Endod J, 2020 Sep;53(9):1199-1203.
    PMID: 32365401 DOI: 10.1111/iej.13318
    Observational studies have a significant role in establishing the prevalence and incidence of diseases in populations, as well as determining the benefits and risks associated with health-related interventions. Observational studies principally encompass cohort, case-control, case series and cross-sectional designs. Inadequate reporting of observational studies is likely to have a negative impact on decision-making in day-to-day clinical practice; however, no reporting guidelines have been published for observational studies in Endodontics. The aim of this project is to develop reporting guidelines for authors when creating manuscripts describing observational studies in the field of Endodontology in an attempt to improve the quality of publications. The new guidelines for observational studies will be named: 'Preferred Reporting items for OBservational studies in Endodontics (PROBE)'. A steering committee was formed by the project leaders (PD, VN) to develop the guidelines through a five-phase consensus process. The steering committee will review and adapt items from the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement and the Clinical and Laboratory Images in Publications (CLIP) principles, as well as identify new items that add value to Endodontics. The steering committee will create a PROBE Delphi Group (PDG), consisting of 30 members across the globe to review and refine the draft checklist items and flowchart. The items will be assessed by the PDG on a nine-point Likert scale for relevance and inclusion. The agreed items will then be discussed by a PROBE Face-to-Face meeting group (PFMG) made up of 20 individuals to further refine the guidelines. After receiving feedback from the PFMG, the steering committee will pilot and finalize the guidelines. The approved PROBE guidelines will be disseminated through publication in relevant journals, and be presented at national and international conferences. The PROBE checklist and flowchart will be available and downloadable from the Preferred Reporting Items for study Designs in Endodontics (PRIDE) website: www.pride-endodonticguidelines.org. The PROBE steering committee encourages clinicians, researchers, editors and peer reviewers to provide feedback on the PROBE guidelines to inform the steering group when the guidelines are updated.
  2. Plotino G, Nagendrababu V, Bukiet F, Grande NM, Veettil SK, De-Deus G, et al.
    J Endod, 2020 Jun;46(6):707-729.
    PMID: 32334856 DOI: 10.1016/j.joen.2020.01.023
    INTRODUCTION: Negotiation, glide path, and preflaring are essential steps in root canal shaping procedures. This report aimed to discuss the terminology, basic concepts, and clinical considerations of negotiation, glide path, and preflaring procedures and the influence of these steps on root canal shaping.

    METHODS: This systematic review was undertaken following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol has been registered with the International Prospective Register of Systematic Reviews (number CRD42019127021). A comprehensive literature search was performed by 2 independent reviewers using a selected search strategy in 2 electronic databases (PubMed and Scopus) until January 28, 2019. A further search was performed manually in endodontic journals. Studies investigating or comparing at least 1 shaping property resulting from root canal instrumentation with a glide path or preflaring in human extracted teeth or clinical studies were included.

    RESULTS: The literature shows that the definition of glide path and preflaring procedures remains controversial, which requires an elaboration in the American Association of Endodontists' Glossary of Endodontic Terms. After the removal of irrelevant and duplicated articles, 98 articles were included. The impact of glide path preparation and preflaring on working length determination, apical file size determination, canal transportation, separation of endodontic files, shaping time, dentinal microcrack formation, and extrusion of debris was discussed. Because of heterogeneity among the included studies, quantitative synthesis was not performed for most of the parameters.

    CONCLUSIONS: An evidence-based guideline is needed to define and correlate the basic concepts and current applications of each step of contemporary advancements in root canal instruments. Glide path preparation reduces the risk of debris extrusion, has no influence on the incidence of dentinal crack formation, and improves the preservation of the original canal anatomy. The creation of a glide path may have no impact on Reciproc files (VDW, Munich, Germany) in reaching the full working length. Preflaring increases the accuracy of working length determination. Further randomized clinical trials are required to evaluate the effect of a glide path and preflaring on root canal treatment outcomes.

  3. Nagendrababu V, Faggion CM, Pulikkotil SJ, Alatta A, Dummer PMH
    Int Endod J, 2022 Jan 26.
    PMID: 35080025 DOI: 10.1111/iej.13693
    AIM: The aims of the study were to assess the methodological quality of systematic reviews with network meta-analyses (NMAs) in Endodontics using the "A MeaSurement Tool to Assess systematic Reviews" (AMSTAR 2) tool, and to evaluate the overall confidence in the results of the individual reviews included in the analysis.

    METHODOLOGY: Systematic reviews with NMAs within the specialty of Endodontics published in English were identified from the PubMed, EbBSCOhost and SCOPUS databases from inception to July 2021. Two reviewers were involved independently in the selection of the reviews, data extraction, methodological quality assessment and overall confidence rating. Disagreements were resolved by discussion between the reviewers to achieve consensus; if disagreements persisted, a third reviewer made the final decision. The methodological quality of the included NMAs was appraised using the AMSTAR 2 checklist, which contains 16 items. The reviewers scored each item - 'Yes' - when the item was fully addressed, 'Partial Yes' - when the item was not fully addressed, or 'No' - when the item was not addressed. The overall confidence in the results of each review was classified as 'High', 'Moderate', 'Low' or 'Critically low' based on the criteria reported by the AMSTAR 2 developers.

    RESULTS: Twelve systematic reviews with NMAs were included. All the NMAs adequately reported Item 1 ("Did the research questions and inclusion criteria for the review include the components of PICO?"), Item 8 ("Did the review authors describe the included studies in adequate detail?"), Item 9 ("Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review?") and Item 16 ("Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?") , whereas only one NMA reported Item 10 adequately ("Did the review authors report on the sources of funding for the studies included in the review?"). The overall confidence in the results of eight reviews was categorised as "Critically low", one review was "Low", two reviews were "Moderate" and one review was "High".

    CONCLUSION: The overall confidence in the results for the majority of systematic reviews with NMAs in Endodontics was judged to be 'Critically low' as their methodological quality was below the necessary standard. AMSTAR 2 and PRISMA for NMA guidelines are available to guide authors to produce high quality systematic reviews with NMAs and for Editors and peer-reviewers when assessing submissions to journals.

  4. Nagendrababu V, Sheriff Sultan O, Kannathasan S, Patel AS, Chitra E, Neelakantan P, et al.
    Restor Dent Endod, 2018 Feb;43(1):e1.
    PMID: 29487832 DOI: 10.5395/rde.2018.43.e1
    Objectives: To determine the effect of root canal irrigants on the hydrophobicity and adherence ofStaphylococcus epidermidis(S. epidermidis) to root canal dentinin vitro.

    Materials and Methods: Root dentin blocks (n= 60) were randomly divided into 4 groups based on the irrigation regimen: group 1, saline; group 2, 5.25% sodium hypochlorite (NaOCl); group 3, 5.25% NaOCl followed by 17% ethylenediaminetetraacetic acid (EDTA); group 4, same as group 3 followed by 2% chlorhexidine (CHX). The hydrophobicity ofS. epidermidisto root dentin was calculated by cell surface hydrophobicity while the adherence was observed by fluorescence microscopy, and bacteria were quantified using ImageJ software (National Institutes of Health). Statistical analysis of the data was done using Kruskal-Wallis test and Mann-WhitneyUtest (p= 0.05).

    Results: The hydrophobicity and adherence ofS. epidermidisto dentin were significantly increased after irrigating with group 3 (NaOCl-EDTA) (p< 0.05), whereas in group 4 (NaOCl-EDTA-CHX) both hydrophobicity and adherence were significantly reduced (p< 0.05).

    Conclusions: The adherence ofS. epidermidisto dentin was influenced differently by root canal irrigants. Final irrigation with CHX reduces the bacterial adherence and may impact biofilm formation.

  5. Varadan P, Ganesh A, Konindala R, Nagendrababu V, Ashok R, Deivanayagam K
    Cureus, 2017 Oct 26;9(10):e1805.
    PMID: 29308333 DOI: 10.7759/cureus.1805
    Introduction Root canal irrigants play an important role in reducing intracanal microorganisms, which in turn helps in achieving a successful outcome for the root canal treatment. Objective To compare the antibacterial efficacy of alexidine and chlorhexidine against Enterococcus faecalis. Methods A total of 50 extracted single-rooted teeth were randomly divided into five groups after being infected with Enterococcus faecalis. The groups were based on irrigants used: Group I - 0.4% alexidine; Group II - 1% alexidine; Group III - 1.5% percent alexidine; Group IV - 2% alexidine; Group V - 2% chlorhexidine. Following irrigation, colony-forming units were determined from the dentinal shavings collected at 400 µm depth. Results Use of 2% alexidine reduced the bacteria effectively when compared to 0.4%, 1%, and 1.5% alexidine. A statistically significant difference was not observed between 2% alexidine and 2% chlorhexidine. Discussion Alexidine, due to its higher virulence factors for bacteria and better bacterial penetrability at 400 µm depth of dentin showed better eradication of Enterococcus faecalis in comparison to chlorhexidine. Conclusion The use of 2% alexidine against Enterococcus faecalis at 400 µm depth of dentin has efficacy comparable to chlorhexidine. Hence, alexidine can be used as an alternative irrigant for chlorhexidine during endodontic procedures.
  6. Ahmed HMA, Nagendrababu V, Duncan HF, Peters OA, Dummer PMH
    Int Endod J, 2023 Jul;56(7):788-791.
    PMID: 37300405 DOI: 10.1111/iej.13918
  7. Nagendrababu V, Narasimhan S, Faggion CM, Dharmarajan L, Jacob PS, Gopinath VK, et al.
    Clin Oral Investig, 2023 Jul;27(7):3437-3445.
    PMID: 36914841 DOI: 10.1007/s00784-023-04948-w
    OBJECTIVES: To evaluate the reporting quality of systematic reviews with network meta-analyses (NMAs) in Endodontics using the the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) for NMA checklist.

    METHODS: The current investigation extends a recently published study in the International Endodontic Journal (Nagendrababu V, Faggion Jr CM, Pulikkotil SJ, Alatta A, Dummer PM Methodological assessment and overall confidence in the results of systematic reviews with network meta-analyses in Endodontics. International Endodontic Journal 2022;55:393-404) that assessed the methodological quality of systematic reviews with NMAs in Endodontics using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) tool. In the present study, the PRISMA for NMA checklist with 32 items was used to assess the reporting quality of the systematic reviews with NMAs (n = 12). Two independent assessors assigned '1' when an item was completely addressed, '0.5' when it was partially addressed, and '0' when it was not addressed. Disagreements were resolved through reviewer discussion until consensus was reached. If conflicts persisted, a third reviewer made the final decision. The PRISMA for NMA scores were shared with the relevant authors of the individual reviews to reduce the likelihood of misinterpretation and verify the scores assigned. The results for each individual item of the PRISMA-NMA items were calculated by summing the individual scores awarded; the maximum score for each item was 12.

    RESULTS: All the systematic reviews with NMAs adequately reported the following items: Title, Introduction section (Objectives), Methods section (Eligibility criteria and Information sources), Results section (Study selection, Study characteristics and Risk of bias within studies), and Discussion section (Summary of evidence). The items that were reported least often were the "geometry of the network" and "the summary of network geometry" with only 2 manuscripts (17%) including these items.

    CONCLUSION: A number of the items in the PRISMA-NMA checklist were adequately addressed in the NMAs; however, none adequately reported all the PRISMA-NMA items. The inadequacies of published NMAs that have been identified should be taken into consideration by authors of NMAs in Endodontics and by editors when managing the peer review process. In future, researchers who are writing systematic reviews with NMAs should comply with the PRISMA-NMA checklist.

    CLINICAL RELEVANCE: None of the included systematic reviews with NMA adequately reported all the PRISMA-NMA items. Inadequate reporting of a systematic review with NMA increases the possibility that it will provide invalid results. Therefore, authors should follow the PRISMA-NMA guidelines when reporting systematic reviews with NMA in Endodontics.

  8. Nagendrababu V, Pulikkotil SJ, Veettil SK, Teerawattanapong N, Setzer FC
    J Endod, 2018 Jun;44(6):914-922.e2.
    PMID: 29709297 DOI: 10.1016/j.joen.2018.02.017
    INTRODUCTION: Successful anesthesia with an inferior alveolar nerve block (IANB) is imperative for treating patients with irreversible pulpitis in mandibular teeth. This systematic review assessed the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) as oral premedications on the success of IANBs in irreversible pulpitis.

    METHODS: Three databases were searched to identify randomized clinical trials (RCTs) published up until September 2017. Retrieved RCTs were evaluated using the revised Cochrane Risk of Bias Tool. The primary efficacy outcome of interest was the success rate of IANB anesthesia. Meta-analytic estimates (risk ratio [RR] with 95% confidence intervals [CIs]) performed using a random effects model and publication bias determined using funnel plot analysis were assessed. Random errors were evaluated with trial sequential analyses, and the quality of evidence was appraised using a Grading of Recommendations, Assessment, Development and Evaluation approach.

    RESULTS: Thirteen RCTs (N = 1034) were included. Eight studies had low risk of bias. Statistical analysis of good-quality RCTs showed a significant beneficial effect of any NSAID in increasing the anesthetic success of IANBs compared with placebo (RR = 1.92; 95% CI, 1.55-2.38). Subgroup analyses showed a similar beneficial effect for ibuprofen, diclofenac, and ketorolac (RR = 1.83 [95% CI, 1.43-2.35], RR = 2.56 [95% CI, 1.46-4.50], and RR = 2.07 [95% CI, 1.47-2.90], respectively). Dose-dependent ibuprofen >400 mg/d (RR = 1.85; 95% CI, 1.39-2.45) was shown to be effective; however, ibuprofen ≤400 mg/d showed no association (RR = 1.78; 95% CI, 0.90-3.55). TSA confirmed conclusive evidence for a beneficial effect of NSAIDs for IANB premedication. The Grading of Recommendations, Assessment, Development and Evaluation approach did not reveal any concerns regarding the quality of the results.

    CONCLUSIONS: Oral premedication with NSAIDs and ibuprofen (>400 mg/d) increased the anesthetic success of IANBs in patients with irreversible pulpitis.

  9. Bardini G, Orrù C, Ideo F, Nagendrababu V, Dummer P, Cotti E
    Aust Endod J, 2023 Sep 13.
    PMID: 37702252 DOI: 10.1111/aej.12794
    This review investigated whether any therapeutic options influenced the outcome of treatment for teeth with external cervical resorption. Out of 870 articles identified by an electronic search, 60 clinical case reports and six case series were included. No randomised clinical trials were found. Risk of bias was assessed using Joanna Briggs Institute's tools. External surgical intervention was the preferred method of accessing the lesions. Removal of resorptive tissue was prevalently achieved mechanically. Bioactive endodontic cements were the preferred materials for restoring teeth. The outcome measures were based on clinical and radiographic parameters. Of the cases included in the review, no specific treatment approach had a superior outcome in relation to Heithersay's classification. Furthermore, due to the absence of randomised clinical trials, and to the low level of evidence associated with case reports/case series, it was not possible to define the optimum clinical treatment for external cervical resorption.
  10. Tomson PL, Vilela Bastos J, Jacimovic J, Jakovljevic A, Pulikkotil SJ, Nagendrababu V
    Int Endod J, 2023 Oct;56 Suppl 3:355-369.
    PMID: 36209498 DOI: 10.1111/iej.13844
    BACKGROUND: Pulpitis characterized by spontaneous pain can result in debilitating pain. Dogma has existed to offer only have two treatment options, namely root canal treatment (RCT) or extraction, although pulpotomy has always remained a potential treatment modality.

    OBJECTIVE: This review aimed to answer the following research question: 'Does pulpotomy (partial or full) (I) result in better patient and clinical reported outcomes (O), compared with RCT (C) in permanent teeth with pulpitis characterized by spontaneous pain (P) evaluated at various time intervals?' (T).

    METHODS: Two authors independently performed study selection, data extraction and risk of bias assessment. The literature search was conducted in the following electronic databases: Clarivate Analytics' Web of Science, Scopus, PubMed and Cochrane Central Register of Controlled Trials. English language clinical trials comparing the patient and clinical reported outcomes between RCT and pulpotomy were included. The meta-analysis was performed on a fixed-effect model and the quality of evidence assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

    RESULTS: Two randomized clinical trials were included. Amongst two trials, one has published four reports at different time points involving the same cohorts. The meta-analysis revealed no difference in postoperative pain (Day 7) between RCT and pulpotomy (OR = 0.99, 95% CI 0.63-1.55, I2  = 0%) and quality of evidence was graded as 'High'. Clinical success was high at year 1, 98% for both interventions, however, decreased over time to 78.1% (pulpotomy) and 75.3% (RCT) at 5 years.

    DISCUSSION: Pulpotomy is a definitive treatment modality that is as effective as RCT. This could have a significant impact on treatment of such patients affording the advantages of retaining a vital pulp and preventing the need for RCT.

    CONCLUSION: This review could only include two trials, hence there is insufficient evidence to draw robust conclusions. The clinical data accumulated so far suggests no difference in pain between RCT and pulpotomy at Day 7 postoperatively and a single randomized control trial suggests that the clinical success rate for both treatment modalities is similar long term. There is a need for more well-designed trials by different research groups to develop a stronger evidence base in this area.

    REGISTRATION: PROSPERO database (CRD42021259744).

  11. Nagendrababu V, Duncan HF, Tsesis I, Sathorn C, Pulikkotil SJ, Dharmarajan L, et al.
    Int Endod J, 2019 Mar 19.
    PMID: 30891775 DOI: 10.1111/iej.13118
    An abstract is a brief overview of a scientific, clinical or review manuscript as well as a stand-alone summary of a conference abstract. Scientists, clinician-scientists and clinicians rely on the summary information provided in the abstracts of systematic reviews to assist in subsequent clinical decision-making. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for Abstracts checklist was developed to improve the quality, accuracy and completeness of abstracts associated with systematic reviews and meta-analyses. The PRISMA for Abstracts checklist provides a framework for authors to follow, which helps them provide in the abstract the key information from the systematic review that is required by stakeholders. The PRISMA for Abstracts checklist contains 12 items (title, objectives, eligibility criteria, information sources, risk of bias, included studies, synthesis of results, description of the effect, strength and limitations, interpretation, funding and systematic review registration) under six sections (title, background, methods, results, discussion, other). The current article highlights the relevance and importance of the items in the PRISMA for Abstracts checklist to the specialty of Endodontology, while offering explanations and specific examples to assist authors when writing abstracts for systematic reviews when reported in manuscripts or submitted to conferences. Strict adherence to the PRISMA for Abstracts checklist by authors, reviewers, and journal editors will result in the consistent publication of high-quality abstracts within Endodontology. This article is protected by copyright. All rights reserved.
  12. Nagendrababu V, Kishen A, Murray PE, Nekoofar MH, de Figueiredo JAP, Priya E, et al.
    Int Endod J, 2019 Sep;52(9):1290-1296.
    PMID: 30985938 DOI: 10.1111/iej.13125
    The regulated use of animals in endodontic research is often necessary to investigate the biological mechanisms of endodontic diseases and to measure the preclinical efficacy, biocompatibility, toxicology and safety of new treatments, biomaterials, sealers, drugs, disinfectants, irrigants, devices and instruments. Animal testing is most crucial in situations when research on humans is not ethical, practical or has unknown health risks. Currently, there is a wide variability in the quality of manuscripts that report the results of animal studies. Towards the goal of improving the quality of publications, guidelines for preventing disability, pain, and suffering to animals, and enhanced reporting requirements for animal research have been developed. These guidelines are referred to as Animals in Research: Reporting In Vivo Experiments (ARRIVE). Henceforth, causing any form of animal suffering for research purposes is not acceptable and cannot be justified under any circumstances. The present report describes a protocol for the development of welfare and reporting guidelines for animal studies conducted in the specialty of Endodontology: the Preferred Reporting Items for Animal Studies in Endodontology (PRIASE) guidelines. The PRIASE guidelines will be developed by adapting and modifying the ARRIVE guidelines and the Clinical and Laboratory Images in Publication (CLIP) principles. The development of the new PRIASE guidelines will include a five-step consensus process. An initial draft of the PRIASE guidelines will be developed by a steering committee. Each item in the draft guidelines will then be evaluated by members of a PRIASE Delphi Group (PDG) for its clarity using a dichotomous scale (yes or no) and suitability for its inclusion using a 9-point Likert scale. The online surveys will continue until each item achieves this standard, and a set of items are agreed for further analysis by a PRIASE Face-to-face Consensus Meeting Group (PFCMG). Following the consensus meeting, the steering committee will finalize and confirm the PRIASE guidelines taking into account the responses and comments of the PFCMG. The PRIASE guidelines will be published and disseminated internationally and updated periodically based on feedback from stakeholders.
  13. Nagendrababu V, Kishen A, Murray PE, Nekoofar MH, de Figueiredo JAP, Priya E, et al.
    Int Endod J, 2021 Jun;54(6):848-857.
    PMID: 33450080 DOI: 10.1111/iej.13477
    Animal testing is crucial in situations when research on humans is not allowed because of unknown health risks and ethical concerns. The current project aims to develop reporting guidelines exclusively for animal studies in Endodontology, using an established consensus-based methodology. The guidelines have been named: Preferred Reporting Items for Animal Studies in Endodontology (PRIASE) 2021. Nine individuals (PD, VN, AK, PM, MN, JF, EP, JJ and SJ), including the project leaders (PD, VN) formed a steering committee. The steering committee developed a novel checklist by adapting and integrating their animal testing and peer review experience with the Animals in Research: Reporting In Vivo Experiments (ARRIVE) guidelines and also the Clinical and Laboratory Images in Publications (CLIP) principles. A PRIASE Delphi Group (PDG) and PRIASE Online Meeting Group (POMG) were also formed. Thirty-one PDG members participated in the online Delphi process and achieved consensus on the checklist items and flowchart that were used to formulate the PRIASE guidelines. The novel PRIASE 2021 guidelines were discussed with the POMG on 9 September 2020 via a Zoom online video call attended by 21 individuals from across the globe and seven steering committee members. Following the discussions, the guidelines were modified and then piloted by several authors whilst writing a manuscript involving research on animals. The PRIASE 2021 guidelines are a checklist consisting of 11 domains and 43 individual items together with a flowchart. The PRIASE 2021 guidelines are focused on improving the methodological principles, reproducibility and quality of animal studies in order to enhance their reliability as well as repeatability to estimate the effects of endodontic treatments and usefulness for guiding future clinical studies on humans.
  14. Nagendrababu V, Kishen A, Murray PE, Nekoofar MH, de Figueiredo JAP, Priya E, et al.
    Int Endod J, 2021 Jun;54(6):858-886.
    PMID: 33492704 DOI: 10.1111/iej.13481
    Laws and ethics require that before conducting human clinical trials, a new material, device or drug may have to undergo testing in animals in order to minimize health risks to humans, unless suitable supporting grandfather data already exist. The Preferred Reporting Items for Animal Studies in Endodontology (PRIASE) 2021 guidelines were developed exclusively for the specialty of Endodontology by integrating and adapting the ARRIVE (Animals in Research: Reporting In Vivo Experiments) guidelines and the Clinical and Laboratory Images in Publications (CLIP) principles using a validated consensus-based methodology. Implementation of the PRIASE 2021 guidelines will reduce potential sources of bias and thus improve the quality, accuracy, reproducibility, completeness and transparency of reports describing animal studies in Endodontology. The PRIASE 2021 guidelines consist of a checklist with 11 domains and 43 individual items and a flowchart. The aim of the current document is to provide an explanation for each item in the PRIASE 2021 checklist and flowchart and is supplemented with examples from the literature in order for readers to understand their significance and to provide usage guidance. A link to the PRIASE 2021 explanation and elaboration document and PRIASE 2021 checklist and flowchart is available on the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org/priase/).
  15. Nagendrababu V, Chong BS, McCabe P, Shah PK, Priya E, Jayaraman J, et al.
    Int Endod J, 2020 May;53(5):619-626.
    PMID: 32090342 DOI: 10.1111/iej.13285
    Case reports can provide early information about new, unusual or rare disease(s), newer treatment strategies, improved therapeutic benefits and adverse effects of interventions or medications. This paper describes the process that led to the development of the Preferred Reporting Items for Case reports in Endodontics (PRICE) 2020 guidelines through a consensus-based methodology. A steering committee was formed with eight members (PD, VN, BC, PM, PS, EP, JJ and SP), including the project leaders (PD, VN). The steering committee developed an initial checklist by combining and modifying the items from the Case Report (CARE) guidelines and Clinical and Laboratory Images in Publications (CLIP) principles. A PRICE Delphi Group (PDG) and PRICE Face-to-Face Meeting Group (PFMG) were then formed. The members of the PDG were invited to participate in an online Delphi process to achieve consensus on the wording and utility of the checklist items and the accompanying flow chart that was created to complement the PRICE 2020 guidelines. The revised PRICE checklist and flow chart developed by the online Delphi process was discussed by the PFMG at a meeting held during the 19th European Society of Endodontology (ESE) Biennial Congress in Vienna, Austria, in September 2019. Following the meeting, the steering committee created a final version of the guidelines, which were piloted by several authors during the writing of a case report. In order to help improve the clarity, completeness and quality of case reports in Endodontics, we encourage authors to use the PRICE 2020 guidelines.
  16. Nagendrababu V, Murray PE, Ordinola-Zapata R, Peters OA, Rôças IN, Siqueira JF, et al.
    Int Endod J, 2019 Aug;52(8):1090-1095.
    PMID: 30908638 DOI: 10.1111/iej.13123
    Laboratory-based research studies are the most common form of research endeavour and make up the majority of manuscripts that are submitted for publication in the field of Endodontology. The scientific information derived from laboratory studies can be used to design a wide range of subsequent studies and clinical trials and may have translational potential to benefit clinical practice. Unfortunately, the majority of laboratory-based articles submitted for publication fail the peer-review step, because unacceptable flaws or substantial limitations are identified. Even when apparently well-conducted laboratory-based articles are peer-reviewed, they can often require substantial corrections prior to the publication. It is apparent that some authors and reviewers may lack the training and experience to have developed a systematic approach to evaluate the quality of laboratory studies. Occasionally, even accepted manuscripts contain limitations that may compromise interpretation of data. To help authors avoid manuscript rejection and correction pitfalls, and to aid editors/reviewers to evaluate manuscripts systematically, the purpose of this project is to establish and publish quality guidelines for authors to report laboratory studies in the field of Endodontology so that the highest standards are achieved. The new guidelines will be named-'Preferred Reporting Items for Laboratory studies in Endodontology' (PRILE). A steering committee was assembled by the project leads to develop the guidelines through a five-phase consensus process. The committee will identify new items as well as review and adapt items from existing guidelines. The items forming the draft guidelines will be reviewed and refined by a PRILE Delphi Group (PDG). The items will be evaluated by the PDG on a nine-point Likert scale for relevance and inclusion. The agreed items will then be discussed by a PRILE face-to-face consensus meeting group (PFCMG) formed by 20 individuals to further refine the guidelines. This will be subject to final approval by the steering committee. The approved PRILE guidelines will be disseminated through publication in relevant journals, presented at congresses/meetings, and be freely available on a dedicated website. Feedback and comments will be solicited from researchers, editors and peer reviewers, who are invited to contact the steering committee with comments to help them update the guidelines periodically.
  17. Nagendrababu V, Duncan HF, Bjørndal L, Kvist T, Priya E, Jayaraman J, et al.
    Int Endod J, 2020 Jun;53(6):764-773.
    PMID: 32196696 DOI: 10.1111/iej.13294
    In evidence-based health care, randomized clinical trials provide the most accurate and reliable information on the effectiveness of an intervention. This project aimed to develop reporting guidelines, exclusively for randomized clinical trials in the dental specialty of Endodontology, using a well-documented, validated consensus-based methodology. The guidelines have been named Preferred Reporting Items for RAndomized Trials in Endodontics (PRIRATE) 2020. A total of eight individuals (PD, VN, HD, LB, TK, JJ, EP and SP), including the project leaders (PD and VN) formed a steering committee. The committee developed a checklist based on the items in the Consolidated Standards of Reporting Trials (CONSORT) guidelines and Clinical and Laboratory Images in Publications (CLIP) principles. A PRIRATE Delphi Group (PDG) and PRIRATE Face-to-Face Meeting group (PFMG) were also formed. Thirty PDG members participated in the online Delphi process and achieved consensus on the checklist items and flowchart that make up the PRIRATE guidelines. The guidelines were discussed at a meeting of the PFMG at the 19th European Society of Endodontology (ESE) Biennial congress, held on 13 September 2019 in Vienna, Austria. A total of 21 individuals from across the globe and four steering committee members (PD, VN, HD and LB) attended the meeting. As a consequence of the discussions, the guidelines were modified and then piloted by several authors whilst writing a manuscript. The PRIRATE 2020 guidelines contain a checklist consisting of 11 sections and 58 individual items as well as a flowchart, considered essential for authors to include when writing manuscripts for randomized clinical trials in Endodontics.
  18. Daood U, Bapat RA, Sidhu P, Ilyas MS, Khan AS, Mak KK, et al.
    Dent Mater, 2021 10;37(10):1511-1528.
    PMID: 34420798 DOI: 10.1016/j.dental.2021.08.001
    OBJECTIVES: The aim of the current project was to study the antimicrobial efficacy of a newly developed irrigant, k21/E against E. faecalis biofilm.

    METHODS: Root canals were instrumented and randomly divided into the following groups: irrigation with saline, 6% NaOCl (sodium hypochlorite), 6% NaOCl+2% CHX (Chlorhexidine), 2% CHX, 0.5% k21/E (k21 - quaternary ammonium silane) and 1% k21/E. E. faecalis were grown (3-days) (1×107CFU mL-1), treated, and further cultured for 11-days. Specimens were subjected to SEM, confocal and Raman analysis and macrophage vesicles characterized along with effect of lipopolysaccharide treatment. 3T3 mouse-fibroblasts were cultured for alizarin-red with Sortase-A active sites and Schrödinger docking was performed. TEM analysis of root dentin substrate with matrix metalloproteinases profilometry was also included. A cytotoxic test analysis for cell viability was measured by absorbance of human dental pulp cells after exposure to different irrigant solutions for 24h. The test percentages have been highlighted in Table 1.

    RESULTS: Among experimental groups, irrigation with 0.5% k21/E showed phase separation revealing significant bacterial reduction and lower phenylalanine 1003cm-1 and Amide III 1245cm-1 intensities. Damage was observed on bacterial cell membrane after use of k21/E. No difference in exosomes distribution between control and 0.5%k21/E was observed with less TNFα (*p<0.05) and preferential binding of SrtA. TEM images demonstrated integrated collagen fibers in control and 0.5%k21/E specimens and inner bacterial membrane damage after k21/E treatment. The k21 groups appeared to be biocompatible to the dental pulpal cells grown for 24h.

    SIGNIFICANCE: Current investigations highlight potential advantages of 0.5% k21/E as irrigation solution for root canal disinfection.

  19. Nagendrababu V, Abbott PV, Boutsioukis C, Duncan HF, Faggion CM, Kishen A, et al.
    Int Endod J, 2022 Jan 18.
    PMID: 35043398 DOI: 10.1111/iej.13682
    High-quality systematic reviews in the field of Dentistry provide the most definitive overarching evidence for clinicians, guideline developers and healthcare policy makers to judge the foreseeable risks, anticipated benefits, and potential harms of dental treatment. In the process of carrying out a systematic review, it is essential that authors appraise the methodological quality of the primary studies they include, because studies which follow poor methodology will have a potentially serious negative impact on the overall strength of the evidence and the recommendations that can be drawn. In Endodontology, systematic reviews of laboratory studies have used quality assessment criteria developed subjectively by the individual authors as there are no comprehensive, well-structured, and universally accepted criteria that can be applied objectively and universally to individual studies included in reviews. Unfortunately, these subjective criteria are likely to be inaccurately defined, unreliably applied, inadequately analysed, unreasonably biased, defective, and non-repeatable. The aim of the present paper is to outline the process to be followed in the development of comprehensive methodological quality assessment criteria to be used when evaluating laboratory studies, that is research not conducted in vivo on humans or animals, included in systematic reviews within Endodontology. The development of new methodological quality assessment criteria for appraising the laboratory-based studies included in systematic reviews within Endodontology will follow a three-stage process. First, a steering committee will be formed by the project leaders to develop a preliminary list of assessment criteria by modifying and adapting those already available, but with the addition of several new items relevant for Endodontology. The initial draft assessment criteria will be reviewed and refined by a Delphi Group (n = 40) for their relevance and inclusion using a nine-point Likert scale. Second, the agreed items will then be discussed in an online or face-to-face meeting by a group of experts (n = 10) to further refine the assessment criteria. Third, based on the feedback received from the online/face-to-face meeting, the steering committee will revise the quality assessment criteria and subsequently a group of authors will be selected to pilot the new system. Based on the feedback collected, the criteria may be revised further before being approved by the steering committee. The assessment criteria will be published in relevant journals, presented at national and international congresses/meetings, and will be freely available on a dedicated website. The steering committee will update the assessment criteria periodically based on feedback received from end-users.
  20. Keong JY, Low LW, Chong JM, Ong YY, Pulikkotil SJ, Singh G, et al.
    Saudi Dent J, 2020 Mar;32(3):148-154.
    PMID: 32180672 DOI: 10.1016/j.sdentj.2019.08.001
    PURPOSE: Periodontal ligament stem cells (PDLSCs) have considerable potential for use as a means of achieving periodontal regeneration due to their noteworthy proliferative properties and secretory functions. In particular, PDLSCs secrete vascular endothelial growth factor (VEGF) which enhances angiogenesis and osteogenesis. The resulting repair and development of blood vessels and hard tissues which would occur in the presence of these cells could be central to an effective periodontal regeneration procedure.The bacterial biofilm of tooth surface related to the periodontium might provide either an inhibition or a stimulus to different factors involved in a regenerative process. Cell culture experiments have been investigated in vitro by adding lipopolysaccharide (LPS) to the culture medium but the effect of various concentration of LPS in these circumstances has not been investigated. Therefore, this study aimed to investigate the effect of LPS concentrations on proliferation of PDLSCs in vitro and on their secretion of VEGF.

    MATERIALS AND METHODS: PDLSCs were treated with 0, 5, 10 and 20 µg/mL of Escherichia coli LPS. At 48 and 96 h, total cell numbers of control and LPS treated PDLSCs were counted by haemocytometer under a microscope. The VEGF concentration in the conditioned media of the PDLSCs was measured by ELISA.

    RESULTS: Rate of cell proliferation of PDLSCs decreased significantly in all LPS treated groups at both 48 h and 96 h except for the group treated with 5 µg/mL of LPS at 48 h. At both 48 and 96 h, VEGF secretion from PDLSCs was reduced significantly at all three LPS concentrations. There was no statistically significant difference in cell proliferation and the amount of VEGF secretion of PDLSCs among the groups treated with different LPS concentrations. No statistically significant change was found in cell proliferation of LPS treated PDLSCs over time, whereas VEGF secretion of PDLSCs was found to have increased significantly with time despite the LPS treatment.

    CONCLUSIONS: LPS reduced cell proliferation and VEGF secretion of PDLSCs, suggesting that periodontal pathogens might reduce the capability of PDLSCs in periodontal regeneration. Yet, LPS treated PDLSCs remained viable and VEGF secretion increased significantly over time. Further research is needed to study the potential use of PDLSCs in periodontal regeneration and the relationship of biofilm LPS accumulations.

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