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  1. Nagendrababu V, Pulikkotil SJ, Suresh A, Veettil SK, Bhatia S, Setzer FC
    Int Endod J, 2019 Jun;52(6):779-789.
    PMID: 30638269 DOI: 10.1111/iej.13072
    The management of pain during root canal treatment is important. The aim of this systematic review and network meta-analysis was to identify the anaesthetic solution that would provide the best pulpal anaesthesia for inferior alveolar nerve blocks (IANB) treating mandibular teeth with irreversible pulpitis. Two electronic databases (PubMed and Scopus) were searched to identify studies up to October 2018. Randomized clinical trials comparing at least two anaesthetic solutions (lidocaine (lignocaine), articaine, bupivacaine, prilocaine or mepivacaine) used for IANB for treatment of irreversible pulpitis were included. The revised Cochrane risk of bias tool for randomized trials was used to assess the quality of the included studies. Pairwise meta-analysis, network meta-analysis using a random-effects model, and SUCRA ranking were performed. The network meta-analysis estimated the probability of each treatment performing best. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. In total, 11 studies (n = 750) were included in the meta-analysis. The network meta-analysis revealed that only mepivacaine significantly increased the success rate of IANB compared to lidocaine (RR, 1.42 [95% CI 1.04-1.95]). However, no significant differences in the success rate of IANB were observed between mepivacaine and other anaesthetic agents (articaine and bupivacaine). Of all anaesthetic agents, mepivacaine (SUCRA = 0.81) ranked first in increasing the success rate of IANB, followed by prilocaine (SUCRA = 0.62), articaine (SUCRA = 0.54), bupivacaine (SUCRA = 0.41) and lidocaine (SUCRA = 0.13). The overall quality of evidence was very low to moderate. In conclusion, based on the evidence from the randomized clinical trials included in this review, mepivacaine with epinephrine demonstrated the highest probability of providing effective pulpal anaesthesia using IANB for teeth with irreversible pulpitis compared to prilocaine, articaine, bupivacaine and lidocaine. Further, high-quality clinical trials are needed to support the conclusion of this review.
  2. Pulikkotil SJ, Nagendrababu V, Veettil SK, Jinatongthai P, Setzer FC
    Int Endod J, 2018 Sep;51(9):989-1004.
    PMID: 29480930 DOI: 10.1111/iej.12912
    This systematic review (SR; PROSPERO database: CRD42017075160) and network meta-analysis (NMA) identified the most effective oral premedication for anaesthetic success of inferior alveolar nerve blocks (IANB) in cases of irreversible pulpitis. Medline and Ebscohost databases were searched up until 10/2017. Randomized controlled trials (RCT) studying the effect of oral premedication, alone or in combination, on the success of IANB for cases of irreversible pulpitis, compared to placebo or other oral premedications, were included. Quality of the included studies was appraised by the revised Cochrane risk of bias tool for randomized trials. Pairwise analysis, NMA and quality of evidence assessment using GRADE criteria were performed. Nineteen studies (n = 1654 participants) were included. NMA demonstrated that compared to placebo, dexamethasone was most effective in increasing anaesthetic success (RR, 2.92 [95% CI 1.74,4.91]; SUCRA = 0.96), followed by NSAIDs (RR, 1.92 [95% CI 1.63,2.27], SUCRA = 0.738) and Tramadol (RR, 2.03 [95% CI 1.18,3.49], SUCRA = 0.737). Premedication with acetaminophen added to NSAIDs demonstrated similar efficacy as NSAIDs alone (RR, 1.06 [95% CI 0.79,1.43]). Sensitivity analyses proved the superiority of dexamethasone or NSAIDs over any other premedications. Subgroup analyses of specific dosages in comparison with placebo demonstrated that dexamethasone 0.5 mg was most effective, followed by ketorolac 10 mg, piroxicam 20 mg, ibuprofen 400 mg + acetaminophen 500 mg and Tramadol 50 mg. Ibuprofen 400 mg, 600 mg and 800 mg had a significantly improved IANB success, while Ibuprofen 300 mg had no effect. Oral premedication with dexamethasone, NSAIDs or Tramadol significantly increased anaesthetic success. More trials are needed to evaluate the premedication effects of dexamethasone or Tramadol for improved anaesthetic success of IANB when treating irreversible pulpitis.
  3. Nagendrababu V, Dilokthornsakul P, Jinatongthai P, Veettil SK, Pulikkotil SJ, Duncan HF, et al.
    Int Endod J, 2020 Feb;53(2):232-249.
    PMID: 31520403 DOI: 10.1111/iej.13217
    A systematic review aims to answer a focussed research question through a structured review of the evidence, using a predefined methodology, which often includes a meta-analysis. A meta-analysis is a statistical method used to combine the effect estimates from the individual studies included in a systematic review. Systematic reviews and meta-analyses are positioned at the highest level in the hierarchy of clinical evidence. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was introduced in 2009 to help authors improve the quality and reliability of systematic reviews and meta-analyses. Recently, the volume of systematic reviews and meta-analyses in the field of Endodontology has increased; however, the quality of the published manuscripts has been reported to be sub-optimal, which does not take account of the systematic reviews that were rejected because of more obvious deficiencies. The aim of this paper is to present a comprehensive glossary of terminology commonly used in systematic reviews and meta-analyses in an attempt to provide easily understood definitions and explanations to assist authors when reporting systematic reviews and meta-analyses and to allow those wishing to read them to become better informed.
  4. Nagendrababu V, Duncan HF, Whitworth J, Nekoofar MH, Pulikkotil SJ, Veettil SK, et al.
    Int Endod J, 2020 Feb;53(2):200-213.
    PMID: 31491042 DOI: 10.1111/iej.13215
    BACKGROUND: Pain management can be challenging during root canal treatment of teeth with irreversible pulpitis.

    AIM: To identify whether articaine or lidocaine is the most appropriate local anaesthetic solution for teeth with irreversible pulpitis undergoing root canal treatment.

    DATA SOURCE: The protocol of this umbrella review is registered in the PROSPERO database (CRD42019137624). PubMed, EBSCHO host and Scopus databases were searched until June 2019.

    STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Systematic reviews published in English comparing the effectiveness of local anaesthesia following administration of articaine or lidocaine in patients undergoing root canal treatment of teeth diagnosed with irreversible pulpitis were included. Two independent reviewers selected the studies and carried out the data extraction and the appraisal of the included reviews. Disagreements were resolved in consultation with a third reviewer.

    STUDY APPRAISAL AND SYNTHESIS METHODS: The quality of the included reviews was appraised by two independent reviewers using the AMSTAR tool (a measurement tool to assess systematic reviews). Each of the 11 AMSTAR items was given a score of 1 if the specific criterion was met, or 0 if the criterion was not met or the information was unclear.

    RESULTS: Five systematic reviews with meta-analyses were included. The AMSTAR score for the reviews ranged from 8 to 11, out of a maximum score of 11, and all reviews were categorized as 'high' quality. Two reviews scored 0 for item 8 in AMSTAR because the scientific quality of the clinical trials included in these reviews was not used in the formulation of the conclusions.

    LIMITATIONS: Systematic reviews published only in the English language were included. Only a small number of studies were available to assess pain intensity during the injection phase, the time until the onset of anaesthesia and the occurrence of adverse events.

    CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Articaine is more effective than lidocaine for local anaesthesia of teeth with irreversible pulpitis undergoing root canal treatment. There is limited evidence that injection of articaine is less painful, has more rapid onset and has fewer adverse events compared with lidocaine.

  5. Gopinath D, Kunnath Menon R, K Veettil S, George Botelho M, Johnson NW
    Cancers (Basel), 2020 Jul 14;12(7).
    PMID: 32674369 DOI: 10.3390/cancers12071893
    Whether "periodontal disease" can be considered as an independent risk factor for head and neck cancer (HNC) remains controversial. The aim of the current meta-analysis was to quantitatively assess this relationship in order to determine whether this represents a true risk factor, with implications for cancer prevention and management. PubMed, Scopus, and Embase databases were systematically searched. Selective studies were reviewed, and meta-analysis was performed to estimate the pooled odds ratio (OR) with 95% confidence intervals (CIs) on eligible studies using a random effects model. In total, 21 eligible observational studies (4 cohorts and 17 case-controls) were identified for qualitative synthesis after a review of 1051 articles. Significant heterogeneity could be identified in measures utilized for reporting of periodontal disease. Meta-analysis performed on nine studies that employed objective measures for reporting periodontal disease demonstrated a significant association between periodontal disease and HNC [OR 3.17, 95% CI, 1.78-5.64]. A diseased periodontium represents an independent risk marker, and a putative risk factor, for HNC. Prospective studies with standardized measures of periodontal disease severity and extent, integrated with microbiological and host susceptibility facets, are needed to elucidate the mechanisms of this positive association and whether treatment of the former influences the incidence and outcomes for HNC.
  6. Nagendrababu V, Abbott PV, Pulikkotil SJ, Veettil SK, Dummer PMH
    Int Endod J, 2021 Mar;54(3):331-342.
    PMID: 33040335 DOI: 10.1111/iej.13428
    BACKGROUND: The scientific literature is contradictory in relation to selecting the appropriate volume of local anaesthetic solution for inferior alveolar nerve blocks (IANB) when attempting to anaesthetize mandibular teeth with irreversible pulpitis.

    OBJECTIVES: To compare the efficacy of 1.8 and 3.6 mL of the same anaesthetic solution for IANBs when treating mandibular teeth with irreversible pulpitis.

    METHODS: A literature search was performed in PubMed, Scopus and EBSCOhost databases until May 2020. Randomized clinical trials published in English, comparing 1.8 with 3.6 mL of the same anaesthetic solution for IANBs in permanent mandibular teeth with irreversible pulpitis, were included. The risk of bias of the included trials was appraised using the revised Cochrane risk of bias tool. A meta-analysis was performed using the random-effects model. The effect of random errors on the results of the meta-analysis was evaluated by trial sequential analysis and the quality of evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

    RESULTS: Four clinical trials involving 280 teeth from patients with ages ranging from 18 to 65 years were included. Among the four trials, three were categorized as having a 'low' risk of bias and one was categorized as having 'some concerns'. The primary meta-analysis revealed that 3.6 mL of anaesthetic solution when administered for IANBs was associated with significantly greater success rates compared with 1.8 mL (RR = 1.94; 95% CI, 1.07, 3.52; I2  = 77%). Similarly, the results of the sensitivity analysis (restricting trials only to those that used the Heft-Parker visual analogue pain scale) revealed that the use of 3.6 mL significantly increased the success of IANBs compared with 1.8 mL. The trial sequential analysis confirmed the evidence for the beneficial effect of 3.6 mL to achieve success for IANBs was 'conclusive'. The quality of evidence was graded as 'high'.

    CONCLUSION: Increasing the volume of anaesthetic solution from 1.8 to 3.6 mL improved the success rate for IANBs in mandibular molars with irreversible pulpitis. The quality of the evidence was 'high'. Future high-quality clinical trials are required with different types of anaesthetic solutions and other types of teeth.

  7. Iqbal MS, Iqbal MZ, Barua A, Veettil SK, Wei LY, Kit LW, et al.
    Value Health, 2014 Nov;17(7):A594.
    PMID: 27202037 DOI: 10.1016/j.jval.2014.08.2046
    OBJECTIVES. Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) appears to be the main reason of hospitalization in COPD patients. Since substantial economic burden of COPD have not been previously studied in Malaysia, this study aimed at estimating and identifying different costs and related burden of illness in patients receiving treatment of AECOPD in a tertiary care hospital in Malaysia.
    METHODS. A prospective follow-up study was performed in Department of Accident and Emergency and Respiratory Medicine of the hospital. Data were derived on the basis of per exacerbation episode. Relationship between direct medical costs and disease severity was analyzed using various descriptive and inferential statistical approaches.
    RESULTS. Median actual direct medical costs and out-of-pocket costs were RM 457.68 (US$ 141.97) and RM 28.25 (US$ 8.76) per exacerbation respectively. Drug cost (41%) was the leading cost driver, followed by unit cost of treatment per bed (33.6%) and lab investigation cost (25.4%). However, food cost (44.2%) represented the largest proportion in out-of-pocket costs. More than 90% of actual direct medical costs were supported by the Government of Malaysia in the patients studied.
    CONCLUSIONS. Impacts of AECOPD in health care resources are worthy of attention. Cost information from pharmacoeconomic studies is important in decision making for health care professionals and policy makers in order to improve health care outcome and minimize costs.
  8. Iqbal MS, Iqbal MZ, Barua A, Veettil SK, Ling TK, Yong NB, et al.
    Value Health, 2014 Nov;17(7):A594.
    PMID: 27202038 DOI: 10.1016/j.jval.2014.08.2045
    Objectives: The cost of acute exacerbations of asthma had not been well studied in literature. The aim of this study was to identify and quantify the (average) cost of moderate and severe exacerbations of asthma in patients attending tertiary-care setup in Malaysia. The related burden of exacerbations was also calculated.
    Methods: The costs including lab investigation charges, unit costs of treatment per bed, medication charges, food costs, transportation costs and loss of productivity were calculated per asthma episode. Data was analysed by Statistical Package for the Social Sciences (SPSS) version 18.0 using various descriptive and inferential statistical tests.
    Results: A median medical cost of acute exacerbation of asthma under Ministry of Health’s (MOH) perspective was USD 105.00 (RM338.47) per episode. Medication cost comprised the majority (52.38%) of the total medical costs. A median medical cost of acute exacerbation of asthma under patient’s perspective was USD 1.55 (RM4.99) per episode. ConclusionsAsthma exacerbation and length of stay in the hospital were proportional to the direct medical costs. In Malaysia, a substantial proportion of the direct medical cost of asthma treatment is heavily subsidised for the locals.
  9. Sadoyu S, Tanni KA, Punrum N, Paengtrai S, Kategaew W, Promchit N, et al.
    PLoS One, 2022;17(6):e0269009.
    PMID: 35675337 DOI: 10.1371/journal.pone.0269009
    INTRODUCTION: The number of umbrella reviews (URs) that compiled systematic reviews and meta-analysis (SR-MAs) has increased dramatically over recent years. No formal guidance for assessing the certainty of evidence in URs of meta-analyses exists nowadays. URs of non-interventional studies help establish evidence linking exposure to certain health outcomes in a population. This study aims to identify and describe the methodological approaches for assessing the certainty of the evidence in published URs of non-interventions.

    METHODS: We searched from 3 databases including PubMed, Embase, and The Cochrane Library from May 2010 to September 2021. We included URs that included SR-MAs of studies with non-interventions. Two independent reviewers screened and extracted data. We compared URs characteristics stratified by publication year, journal ranking, journal impact factor using Chi-square test.

    RESULTS: Ninety-nine URs have been included. Most were SR-MAs of observational studies evaluating association of non-modifiable risk factors with some outcomes. Only half (56.6%) of the included URs assessed the certainty of the evidence. The most frequently used criteria is credibility assessment (80.4%), followed by GRADE approach (14.3%). URs published in journals with higher journal impact factor assessed certainty of evidence than URs published in lower impact group (77.1 versus 37.2% respectively, p < 0.05). However, criteria for credibility assessment used in four of the seven URs that were published in top ranking journals were slightly varied.

    CONCLUSIONS: Half of URs of MAs of non-interventional studies have assessed the certainty of the evidence, in which criteria for credibility assessment was the commonly used method. Guidance and standards are required to ensure the methodological rigor and consistency of certainty of evidence assessment for URs.

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