Displaying publications 1 - 20 of 27 in total

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  1. Gopinath D, Menon RK
    Methods Mol Biol, 2021;2327:1-15.
    PMID: 34410636 DOI: 10.1007/978-1-0716-1518-8_1
    Evidence on the role of the oral microbiome in health and disease is changing the way we understand, diagnose, and treat ailments. Numerous studies on diseases affecting the oral cavity have revealed a large amount of data that is invaluable for the advancements in diagnosing and treating these diseases. However, the clinical translation of most of these exploratory data is stalled by variable methodology between studies and non-uniform reporting of the data.Understanding the key areas that are gateways to bias in microbiome studies is imperative to overcome this challenge faced by oral microbiome research. Bias can be multifactorial and may be introduced in a microbiome research study during the formulation of the study design, sample collection and storage, or the sample processing protocols before sequencing. This chapter summarizes the recommendations from literature to eliminate bias in the microbiome research studies and to ensure the reproducibility of the microbiome research data.
  2. Menon RK, Gopinath D, Li KY, Leung YY, Botelho MG
    Int J Oral Maxillofac Surg, 2019 Feb;48(2):263-273.
    PMID: 30145064 DOI: 10.1016/j.ijom.2018.08.002
    The objectives of this systematic review were to investigate the efficacy of amoxicillin/amoxicillin-clavulanic acid for reducing the risk of postoperative infection after third molar surgery and to evaluate the adverse outcomes in these patients, as well as in healthy volunteers. A systematic search of four databases was performed on May 26, 2017. Eleven studies qualified for the qualitative analysis and eight were found suitable for meta-analysis. The results suggest that both amoxicillin-clavulanic acid and amoxicillin significantly reduce the risk of infection after third molar extraction (overall relative risk (RR) 0.25, P<0.001). However, with the exclusion of randomized controlled trials with a split-mouth design (due to an inadequate crossover period after antibiotic treatment), only amoxicillin-clavulanic acid was found to be effective (RR 0.21, P<0.001). The risk of adverse effects was significantly higher in the amoxicillin-clavulanic acid group (RR=4.12, P=0.023) than in the amoxicillin group (RR 1.57, P=0.405). In conclusion, amoxicillin-clavulanic acid and amoxicillin may significantly reduce the risk of infection after third molar extraction. However, their use in third molar surgery should be viewed with caution, as recent clinical trials on healthy volunteers have shown evidence of the negative impact of amoxicillin use on bacterial diversity and antibiotic resistance.
  3. Menon RK, Kar Yan L, Gopinath D, Botelho MG
    J Investig Clin Dent, 2019 Nov;10(4):e12460.
    PMID: 31608608 DOI: 10.1111/jicd.12460
    AIM: Randomized controlled trials might be reporting a higher postoperative infection rate for third molar surgery compared to other study designs due to unclear criteria for the classification of "infections". The aim of the present retrospective study was to assess the infection rate after third molar surgery with and without postoperative antibiotic prescription.

    METHODS: Case records of patients who underwent third molar extractions at the Prince Philip Dental Hospital in Hong Kong between 3 July 2012 and 22 June 2017 were evaluated retrospectively. Data extraction was performed for indications, clinical and radiographic findings, antibiotic treatment, postoperative complications, and treatment for postoperative infection. The odds ratio (OR) for postoperative infection was estimated.

    RESULTS: In total, 1615 extracted over 5 years from 992 patient records were included in the final analysis. Antibiotics were prescribed postoperatively for 44% of the extractions. The overall infection rate was 2.05%. There was no significant difference in infection rates between the groups which underwent extractions with or without antibiotics (OR = .68; P = .289). We found a significantly higher risk for infections with increasing age (P = .002).

    CONCLUSION: Infection rates after third molar extraction is minimal in the current setting, with no significant benefit from postoperative antibiotic prescription.

  4. Al-Rudayni AHM, Gopinath D, Maharajan MK, Menon RK
    Transl Cancer Res, 2020 Apr;9(4):3126-3134.
    PMID: 35117676 DOI: 10.21037/tcr.2020.02.77
    Oral mucositis (OM) is one of the most prominent side effects of cancer treatment and is believed to have a significant impact on the quality of life (QoL) of the affected patients. However, measurements for the investigation of OM is plagued by heterogeneity in symptoms that varies with the type of cancer or the treatment. We aimed to carry out a qualitative assessment of the current evidence on the impact of OM on QoL in patients undergoing oncologic treatment. A systematic search for studies evaluating the impact of OM on QoL was performed in MEDLINE and Embase databases from inception to December 2018 using the MeSH terms for the keywords "Antineoplastic", "Stomatitis", and "Quality of life". Studies were initially assessed based on the selection criteria and underwent a selection process based on the title and abstract followed by a full text review. Data extraction was performed into a standardized data collection form to collect data pertaining to the author/year, study design, study characteristics, mucositis assessment, QoL assessment and results. A qualitative assessment was performed. A total of 459 articles were selected after removal of duplicates. Following the full text review, only ten articles qualified for the systematic review based on the selection criteria. Several studies have identified a correlation between the severity of mucositis and reduction in QoL. The impact of OM on QoL extend beyond the local oral complications and has been shown to affect the physical, emotional, and psychological functional domains. However, heterogeneity in the study parameters and evaluation (cancer types, treatment regimens, chosen time points (during or after therapy) and the instruments used for QoL measurements) does not permit a robust assessment of the impact of OM on QoL. A standardized approach to the measurement of oral mucositis and evaluation of QoL is required to enhance the utility of QoL data in patients afflicted with oral mucositis following cancer treatment.
  5. Rahman R, Shaikh MH, Gopinath D, Idris A, Johnson NW
    Mol Oral Microbiol, 2023 Apr 04.
    PMID: 37014754 DOI: 10.1111/omi.12412
    Squamous cell carcinoma of the oral cavity (OSCC) is the most common head and neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) globally. Oncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), are known to be co-associated with OSCC and OPSCC cases. However, the reported incidence of HPV and EBV co-infection in OSCCs and OPSCCs globally is unknown. To address this, we performed a formal meta-analysis and systematic review on published studies that report the detection of both EBV and HPV in OSCCs and OPSCCs. Our analysis revealed 18 relevant studies out of a total of 1820 cases (1181 from the oral cavity and 639 from the oropharynx). Overall, HPV and EBV co-infection was found in 11.9% of OSCC and OPSCC cases combined (95% CI: 8-14.1%). Based on anatomical subsite, dual positivity estimates were 10.5% (95% CI: 6.7- 15.1%) for OSCC and 14.2% (95% CI: 9.1-21.3%) for OPSCC. The highest dual positivity rates described were in European countries: for OSCC 34.7% (95% CI: 25.9 - 44.6%) in Sweden and for OPSCC, 23.4% (95% CI: 16.9 - 31.5%) in Poland. Given these substantive prevalence rates, the value of detecting dual infection in the diagnosis and prognosis of these cancers deserves careful longitudinal studies, as do implications for cancer prevention and therapy. We further proposed molecular mechanisms that could explain how HPV and EBV could co-contribute to the aetiology of OSCCs and OPSCCs. This article is protected by copyright. All rights reserved.
  6. Senaratne NLM, Yung On C, Shetty NY, Gopinath D
    Front Oral Health, 2024;5:1310334.
    PMID: 38445094 DOI: 10.3389/froh.2024.1310334
    OBJECTIVE: The study aimed to evaluate the impact of tobacco use on the composition and functions of the oral microbiome in healthy adult humans.

    METHODS: We conducted a systematic search on PubMed, Web of Science, and Cinhal databases for literature published until 15 December 2023, to identify studies that have evaluated the oral microbiome with culture-independent next-generation techniques comparing the oral microbiome of tobacco users and non-users. The search followed the PECO format. The outcomes included changes in microbial diversity and abundance of microbial taxa. The quality assessment was performed using the Newcastle-Ottawa Scale (NOS) (PROSPERO ID CRD42022340151).

    RESULTS: Out of 2,435 articles screened, 36 articles satisfied the eligibility criteria and were selected for full-text review. Despite differences in design, quality, and population characteristics, most studies reported an increase in bacterial diversity and richness in tobacco users. The most notable bacterial taxa enriched in users were Fusobacteria and Actinobacteria at the phylum level and Streptococcus, Prevotella, and Veillonella at the genus level. At the functional level, more similarities could be noted; amino acid metabolism and xenobiotic biodegradation pathways were increased in tobacco users compared to non-users. Most of the studies were of good quality on the NOS scale.

    CONCLUSION: Tobacco smoking influences oral microbial community harmony, and it shows a definitive shift towards a proinflammatory milieu. Heterogeneities were detected due to sampling and other methodological differences, emphasizing the need for greater quality research using standardized methods and reporting.

    SYSTEMATIC REVIEW REGISTRATION: CRD42022340151.

  7. 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.
  8. Daood U, Gopinath D, Pichika MR, Mak KK, Seow LL
    Molecules, 2021 Apr 12;26(8).
    PMID: 33921378 DOI: 10.3390/molecules26082214
    To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38-7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein's binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.
  9. Gopinath D, Menon RK, Banerjee M, Su Yuxiong R, Botelho MG, Johnson NW
    Crit Rev Oncol Hematol, 2019 Jul;139:31-40.
    PMID: 31112880 DOI: 10.1016/j.critrevonc.2019.04.018
    Imbalance within the resident bacterial community (dysbiosis), rather than the presence and activity of a single organism, has been proposed to be associated with, and to influence, the development and progression of various diseases; however, the existence and significance of dysbiosis in oral/oropharyngeal cancer is yet to be clearly established. A systematic search (conducted on 25/01/2018 and updated on 25/05/2018) was performed on three databases (Pubmed, Web of Science & Scopus) to identify studies employing culture-independent methods which investigated the bacterial community in oral/oropharyngeal cancer patients compared to control subjects. Of the 1546 texts screened, only fifteen publications met the pre-determined selection criteria. Data extracted from 731 cases and 809 controls overall, could not identify consistent enrichment of any particular taxon in oral/oropharyngeal cancers, although common taxa could be identified between studies. Six studies reported the enrichment of Fusobacteria in cancer at different taxonomic levels whereas four studies reported an increase in Parvimonas. Changes in microbial diversity remained inconclusive, with four studies showing a higher diversity in controls, three studies showing a higher diversity in tumors and three additional studies showing no difference between tumors and controls. Even though most studies identified a component of dysbiosis in oral/oropharyngeal cancer, methodological and analytical variations prevented a standardized summary, which highlights the necessity for studies of superior quality and magnitude employing standardized methodology and reporting. Indeed an holistic metagenomic approach is likely to be more meaningful, as is understanding of the overall metabolome, rather than a mere enumeration of the organisms present.
  10. Al-Rudayni AHM, Gopinath D, Maharajan MK, Veettil SK, Menon RK
    Curr Oncol, 2021 07 29;28(4):2852-2867.
    PMID: 34436016 DOI: 10.3390/curroncol28040250
    BACKGROUND: This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential analysis, as well as to assess the quality of the results by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

    METHODS: A comprehensive search of three databases including Medline, Embase and Central was performed to identify randomized controlled trials that used oral cryotherapy for the prevention of chemotherapy-induced oral mucositis. The primary outcome was the incidence of oral mucositis for trials employing oral cryotherapy as the intervention for the prevention of oral mucositis. The meta-analysis was performed using the random-effects model and random errors of the meta-analyses were detected by trial sequential analysis.

    RESULTS: A total of 14 RCTs with 1577 participants were included in the present meta-analysis. Patients treated with oral cryotherapy were associated with a significantly lower risk of developing oral mucositis of any grade (risk ratio (RR), 0.67 (95% CI: 0.56-0.81, p < 0.05)). Findings from the subgroup analyses showed that oral cryotherapy significantly reduced the risk of oral mucositis in patients undergoing bone marrow transplantation (RR 0.69, CI: 0.54-0.89, p < 0.05) as well as chemotherapy (RR 0.66, CI: 0.58-0.75, p < 0.05). Findings from the trial sequential analysis suggested that the evidence on oral cryotherapy as a preventive intervention for oral mucositis in patients with solid malignancies receiving conventional chemotherapy was conclusive.

    CONCLUSION: Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials.

  11. Gopinath D, Wie CC, Banerjee M, Thangavelu L, Kumar R P, Nallaswamy D, et al.
    Clin Oral Investig, 2022 Feb;26(2):1647-1656.
    PMID: 34436669 DOI: 10.1007/s00784-021-04137-7
    INTRODUCTION: Smoked, and especially smokeless, tobacco are major causes of oral cancer globally. Here, we examine the oral bacteriome of smokers and of smokeless tobacco users, in comparison to healthy controls, using 16S rRNA gene sequencing.

    METHODS: Oral swab samples were collected from smokers, smokeless tobacco users, and healthy controls (n = 44). Microbial DNA was extracted and the 16S rRNA gene profiled using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and taxonomical classification was performed using the phylogenetic placement method. Differentially abundant taxa were identified using DESeq2, while functional metagenomes based on KEGG orthology abundance were inferred using LIMMA.

    RESULTS: A significantly higher microbial diversity was observed in smokeless tobacco users and smokers relative to controls (P  1.5; BH adj P 

  12. Koe KH, Veettil SK, Maharajan MK, Syeed MS, Nair AB, Gopinath D
    J Evid Based Dent Pract, 2023 Mar;23(1):101778.
    PMID: 36914303 DOI: 10.1016/j.jebdp.2022.101778
    OBJECTIVE: To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials.

    METHODS: A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA).

    RESULTS: A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only.

    CONCLUSION: NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.

  13. Burhanudin NA, Zaini ZM, Rahman ZAA, Ismail SM, Gopinath D, Abraham MT, et al.
    PMID: 36229363 DOI: 10.1016/j.oooo.2022.07.014
    OBJECTIVE: Extranodal extension (ENE) is an important prognostic factor in oral squamous cell carcinoma (OSCC). However, ENE is only confirmed postoperatively by histologic assessment of the lymph nodes after neck dissection. Accurate identification of ENE preoperatively would help in management of OSCC.

    STUDY DESIGN: We determined the expression of molecular markers gamma glutamyl hydrolase (GGH), cyclin-dependent kinase inhibitor-3 (CDKN3), and chromobox homolog-7 (CBX7) using immunohistochemistry in OSCC clinical samples (n = 35). The intensity of staining was scored using a semiquantitative index (HSCORE). The association between clinicopathologic parameters and expression of molecular markers with ENE status was analyzed using chi-square test.

    RESULTS: The number of positive nodes and the highest anatomic level of nodal involvement significantly correlated with ENE (P < .05). High GGH expression was significantly associated with ENE (P < .05), with an increased risk for ENE (odds ratio [OR] 9.9, 95% CI 1.08-91.47, P = .04), whereas no significant association was seen for CDKN3 and CBX7 expression with ENE. However, a trend toward significance was observed with a high level of CDKN3 and a low level of CBX7 expression with ENE.

    CONCLUSIONS: Gamma glutamyl hydrolase offers potential as a predictor for ENE in OSCC, whereas the role of CDKN3 and CBX7 need to be validated in a larger sample.

  14. Senaratne NLM, Chong CW, Yong LS, Yoke LF, Gopinath D
    Front Oral Health, 2023;4:1275717.
    PMID: 38024144 DOI: 10.3389/froh.2023.1275717
    BACKGROUND: While oral mirobial dysbiosis due to tobacco smoking has been studied thoroughly, there is limited data on the effect of waterpipe smoking on the oral microbiome. This study aims to compare the salivary microbiome between waterpipe smokers and non-smokers.

    MATERIALS AND METHODS: Unstimulated saliva samples were collected from 60 participants, 30 smokers and 30 non-smokers in Kuala Lumpur and Klang Valley, Malaysia. DNA extraction was performed using the Qiagen DNA mini kit, and the 16S rRNA bacterial gene was amplified and sequenced using the Illumina MiSeq platform. Sequencing reads were processed using DADA2, and the alpha and beta diversity of the bacterial community was assessed. Significantly differentiated taxa were identified using LEfSe analysis, while differentially expressed pathways were identified using MaAsLin2.

    RESULTS: A significant compositional change (beta diversity) was detected between the two groups (PERMANOVA P 

  15. Cheng YO, Veettil SK, Syeed MS, Shetty NY, Gopinath D
    J Evid Based Dent Pract, 2023 Dec;23(4):101918.
    PMID: 38035895 DOI: 10.1016/j.jebdp.2023.101918
    BACKGROUND: Recurrent aphthous ulceration (RAU) is an oral condition cavity affecting 2.5 billion people worldwide. We aimed to assess the comparative efficacy and safety of available interventions in the management of RAU.

    MATERIALS AND METHODS: An electronic search of 3 databases (Medline, CENTRAL, Scopus) was performed to identify randomized control trials evaluating the efficacy of RAU interventions published until December 2022. A network meta-analysis (NMA) was conducted on 4 outcomes: reduction in pain, duration of ulceration, the diameter of ulceration, and area of ulceration. The interventions are then arranged using the surface area under cumulative ranking (SUCRA).

    RESULTS: A total of 38 trials involving 2773 patients were included were included in quantitative synthesis by NMA. Our analysis showed that Diode laser [MD, -4.865 ± 1.951 (95%CI = (-8.690, -1.041)] was the most effective in reducing the pain score followed by Amlexanox [MD, -2.673 ± 1.075 (95%CI = -4.779, -0.566)]. Iralvex performed the best in reducing the duration of ulceration [MD, -6.481 ± 1.841 (95%CI = -10.090, -2.872)]. Diode laser, acacia nilotica with licorice formulation, and amlexanox were the most effective interventions for reduction of ulcer diameter. Majority of the trials reported absence of any adverse effects and those reported were mild.

    CONCLUSION: Our NMA has identified several interventions to be more effective than a placebo. Laser therapy may be an option for promoting pain management, however, most have only been tested in 1 or 2 trials. Further studies with rigorous methodology on larger samples are recommended to strengthen the current evidence.

  16. Al-Rudayni AHM, Gopinath D, Maharajan MK, Veettil SK, Menon RK
    Int J Environ Res Public Health, 2021 Jul 12;18(14).
    PMID: 34299869 DOI: 10.3390/ijerph18147418
    Oral mucositis is a debilitating complication of chemotherapy, characterized by erythema, ulcers and oedema of the oral mucosa. This review aimed to evaluate the efficacy of Photobiomodulation in the treatment of oral mucositis using meta-analysis and trial sequential analysis, and also to assess the quality of the results by Grading of Recommendations, Assessment, Development and Evaluation (GRADE). A comprehensive search of three databases, including Embase, Medline and Central, was performed to identify randomized controlled trials studying the efficacy of Photobiomodulation in the treatment of cancer chemotherapy-induced oral mucositis. The primary outcome was reduction in the severity of oral mucositis. Secondary outcomes were pain relief, duration of oral mucositis and adverse effects. The meta-analysis was performed using the random-effects model, and random errors of the meta-analyses were detected by trial sequential analysis. A total of 6 randomized controlled trials with 398 participants were included in our analysis. Photobiomodulation significantly reduced the severity of oral mucositis when compared to sham radiation (RR 0.43, 95% CI 0.20 to 0.93; p < 0.05). Sensitivity analysis by excluding trials with high risk of bias reiterated the robustness of our results (RR 0.28, 95% CI 0.16 to 0.48). Trial sequential analysis illustrated that the evidence from the meta-analysis was conclusive. The result of the meta-analyses with trial sequential analysis illustrated that Photobiomodulation is an effective therapeutic intervention for the treatment of oral mucositis, and the evidence gathered can be considered conclusive with a moderate level of certainty according to GRADE. Further trials are recommended to standardize the laser parameters required for the optimal effect.
  17. Aribi Al-Zoobaee FW, Yee Shen L, Veettil SK, Gopinath D, Maharajan MK, Menon RK
    Int J Environ Res Public Health, 2020 Nov 30;17(23).
    PMID: 33265920 DOI: 10.3390/ijerph17238891
    Cancer therapy may be complicated and compromised by viral infections, including oral herpes simplex virus (HSV) infection. This network meta-analysis aimed to identify the best antiviral agent to prevent or treat oral HSV infection in patients being treated for cancer. A search was conducted for trials published since inception until the 10th of May 2020 in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A network meta-analysis was performed on the data from randomized controlled trials that assessed antiviral agents for preventive or therapeutic activity vs. placebo, no treatment or any other active intervention in patients being treated for cancer. The agents were ranked according to their effectiveness in the prevention of oral HSV using surface under the cumulative ranking (SUCRA). Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of the evidence. In total, 16 articles were included. The pooled relative risk (RR) to develop oral HSV infection in the acyclovir group was 0.17 (95% CI: 0.10, 0.30), compared to 0.22 (95% CI: 0.06, 0.77) in the valacyclovir group. Acyclovir ranked highest for the prevention of oral HSV followed by valacyclovir. Subgroup analysis with different acyclovir regimens revealed that the best regimens in terms of HSV-1 prevention were 750 mg/m2 acyclovir administered intravenously followed by 1600 mg per day orally. Acyclovir (250 mg/m2 per day) administered intravenously was the least effective against the prevention of oral HSV.
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