Evidence-Based Bibliometric Analysis of Research on Silver Diamine Fluoride Use in Dentistry

Background This bibliometric analysis is aimed at reviewing the research pattern on the use of silver diamine fluoride (SDF) in dentistry using various citation metrics. Methods A well-curated search was conducted on Elsevier's Scopus database for the relevant literature on SDF published between 1969 and 2021. Bibliographic information such as information related to citations, bibliographic data, abstracts, keywords, and other relevant information was extracted using different combinations of keywords (“silver diamine fluoride” OR “Silver Diamine Fluorides” OR “Diamine Fluoride” OR “Silver Fluoride”). Analysis and visualization of the selected documents and related data were performed using various tools and software including MS Excel, MS Access, Bibexcel, VOS viewer, Biblioshiny, and Gephi. VOS Viewer was utilized for the Graph Modeling Language (GML) to generate graphical representations of the data. Furthermore, network graphs were generated to assess the various associations between research themes, countries, organizations, authors, journals, and citations. Results The initial search yielded 662 documents, of which 410 were chosen for analysis. 252 records were deemed irrelevant. The chosen records consisted of journal articles (n = 351), conference papers (n = 14), book chapters (n = 1), and review articles (n = 44). The results showed that there was an upward trend in the research on SDF, and a substantial increase was observed in the citation index after 2014. Researchers from the United States of America, Hong Kong, and Japan were the top contributors, with organizations and authors from the Faculty of Dentistry, University of Hong Kong, leading the way in citations and productivity. Conclusion The bibliometric analysis provides valuable information regarding the total number of publications on SDF and their citation details. It also identifies the leading countries and organizations involved in the research on SDF and provides a comprehensive analysis of the research trends related to SDF.


Introduction
According to the Global Burden of Diseases, untreated caries in primary dentition are the 10th most common condition currently affecting humans [1]. This has been attributed to several factors such as limited or lack of access to oral health care services in the community, improper exposure to fluoride, and increased consumption of sugary food and beverages. These findings are indicative of the fact that existing therapeutic strategies have not been able to inhibit dental caries. Hence, there is a need to investigate new or alternative approaches to control cariostatic activity in pediatric patients [2]. Silver salts have been extensively mentioned in the current literature for their ability to elicit a potent antimicrobial response in young dentition [3][4][5].
Dr Nishino and Yamaga are considered the pioneers in this field for successfully adapting ammoniacal silver fluoride for arresting dental caries in patients [6]. After the initial experimentation, the existing formulation of these salts was combined with fluoride and silver ions to form silver diamine fluoride (SDF). SDF has been proven to be useful in the management of many dental conditions. It is indicated for managing early childhood caries [7], erosive tooth wear, tooth sensitivity as well as desensitization of noncarious tooth or hypersensitive dentin [8], and molar incisor hypomineralization [9]. SDF is a colorless ammonia solution made of silver and fluoride ions. Since the neutral silver fluoride exists in an unstable form, it is usually mixed with water containing ammonia to give it a more stable structure [10]. The diamine-silver ion is a complex ion with two ammonia molecules connected to a silver ion. The fluoride in the SDF has a well-proven track record for exaggerating the remineralization of enamel and dentine [11], whereas the silver has been proven to have a strong antibacterial activity [12].
In 2014, the Food and Drug Administration (FDA) in the USA cleared SDF to be marketed as a class II medical device that could be used to treat tooth sensitivity. However, it has also being used offlabel to treat and prevent dental caries [13]. The American Dental Association (ADA) Council on Scientific Affairs recommends the biannual application of a 38% SDF solution as the treatment of choice for nonrestorative management of advanced cavitated carious lesions on any coronal surface of permanent or primary teeth [14]. The need for agents like SDF is perhaps best understood in terms of the World Health Organization (WHO) Millennium Development Goals for Health [15]. The proposed path to achieving these goals involves laying more emphasis on emergency care, prevention, and developing newer costeffective interventions [16]. To achieve these goals, simpler technologies would be required to "scale up" dental services and to improve the access to oral health care that is costeffective and affordable. Furthermore, all preventive interventions would need to be built on firm evidence-based foundations. The use of SDF in dentistry for the prevention and treatment of dental caries has gained great momentum over the past few years [4]. Systematic reviews conducted in the past on SDF have reported its use not only in the prevention of dental caries but also in arresting carious lesions in paediatric as well as geriatric patients. Its effect on root caries prevention and arrest is also being explored by different research clusters across the globe [17][18][19].
While SDF has been routinely used in Japan for over 80 years [20], its use is now increasing at the global level. Consequently, there has been growing interest among researchers in investigating the use of SDF in dentistry. The last decade, in particular, has seen exponential growth in the research on SDF. However, a comprehensive analysis of this published research is lacking. There is a need to analyze the published articles on the topic both quantitatively and qualitatively. A comprehensive systemic analysis would help understand the current research on the topic and highlight any gaps that need to be filled. A bibliometric analysis is a quantitative measure that aids to assess the scholarly literature by analysing various aspects of research articles such as citation analysis, publication counts, institutional affiliations, and geographical distribution [21]. Bibliometric indicators aid in measuring, assessing, and comparing the research output and impact of individual researchers, groups, and organizations. Different databases have been used in such analyses such as Scopus (Elsevier, Netherlands), Web of Science (Clarivate Analytics, USA), and Medline (National Library of Medicine (NLM), USA).
This investigation is aimed at reviewing the research progress on silver diamine fluoride in dentistry by using a bibliometric approach. The objective was to analyze research productivity, publication and citation structure, leading countries and institutions, most productive authors, and leading journals, major themes, keyword co-occurrences, bibliographic coupling of countries, authors, and journals from 1969 to 2021 in the field of SDF. It is hoped that this systemic bibliometric analysis would help overcome hurdles amongst research clusters across the globe working on investigating the clinical potential of SDF in dentistry and provide researchers with a comprehensive overview of the current state of affairs regarding research on SDF in dentistry.

Materials and Methods
A bibliometric analysis (a quantitative method) of the academic literature, published on the topic "silver diamine fluoride use in dentistry," was performed in this study. Different variables such as the total citations (TC), total publications (TP), publishing year (PY), journal's impact factor (IF), authorship patterns, and the h-index were identified. The most productive authors, journals, countries, and organizations were also identified from the retrieved data.

Database and Bibliographic Information Selection.
Scopus is a well-known, curated, and high-quality bibliographic database. It was selected for data extraction on publications on "silver diamine fluoride use in dentistry." Bibliographic information related to citations, abstracts, keywords, and other relevant bibliographic information was extracted.

Search
Query. Bibliographic data on silver diamine fluoride use in dentistry was searched by the following query, using the advanced search interface of Scopus: "Article Title, Abstract, Keywords." Search terms were combined by the Boolean operator "OR": "silver diamine fluoride" OR "Silver Diamine Fluorides" OR "Diamine Fluoride" OR "Silver Fluoride." 2.3. Date of Data Extraction. The abovementioned database was searched at the Imam Abdul Rehman Bin Faisal University, Saudi Arabia, on January 13, 2021. The initial search yielded a total of 662 documents.  Figure 1, were applied to extract the most relevant and comprehensive data. The search was limited to articles, review articles, conference papers, books, and book chapters. No language, geographical, or time (date) filters were applied. However, editorials and short surveys were excluded. The initial search yielded 662 documents. Each record was then screened for relevance and eligibility, and 252 irrelevant records were excluded. Conclusively, 410 records consisting of journal articles (n = 351), conference papers (n = 14), book chapters (n = 1 ), and review articles (n = 44) were selected for the bibliometric analysis. The publication date of the selected records ranged from 1969 to 2021. The records were finally exported into MS Excel. To ensure the correctness of data, this process was repeated by two of the authors of the study. 2). The VOSViwere software was used to obtain the Graph Modeling Language (GML) files from the raw data. These GML files were then exported into Gephi for network analysis and network visualization. The bibliometric indicators with respect to citation, documents, sources, authors, organizations, and countries were also studied. Lastly, the publication and citation trends, authorship patterns, bibliographic couplings (journals, countries, and authors), co-occurrences of keywords, cocitation network of authors, and thematic evolution were visualized with the help of the aforementioned tools and software. . Figure 2 shows the annual research productivity in SDF research in terms of publications and citations. It can be seen that the first two publications on the topic were published in the year 1969 and collectively received 31 citations. Since then, the research productivity has progressively increased. There was significant activity during the second decade of the current century (2011-2020) with 317 publications published during the time (77% of the total publications). Furthermore, during the same period, these 317 publications received 3642 citations (62% of the total citations). The maximum number of publications (N = 94) occurred in the year 2020. On the other hand, the 16 publications that were published in the year 2012 were the most highly cited (635 citations) among all.

Publishing and Citation Structure of Silver Diamine
Fluoride. Table 1 Table 1 shows the annual citation structure of silver diamine fluoride research between 1969 and 2021. It also shows the total publications (TP), number of cited publications (NCP), total citations (TC), citation impact [publication] (C/P), and citation impact [cited publication] (C/CP).
3.3. Leading Countries and Institutions. Analysis was conducted to determine the countries and institutes leading the way with the highest number of publications. The citations received by these publications and their citation impact were also calculated as shown in Table 2 As for the leading institutions, the University of Hong Kong topped the list of organizations with the most publications in SDF research. As shown in Table 2 Table 2 lists the top countries and organizations in silver diamine fluoride research between 1969 and 2021. It also shows total publications (TP), total citations (TC) associated with these publications, and citations impact (CI).

Most Productive Authors.
The data was sorted based on total publications from various authors to identify the top 10 most productive authors. The total citations, citation impact, and h-index were also calculated to highlight their respective influence in this area of research. Table 3   Three journals from this list are in the 1 st quartile, two in the 2 nd quartile, three in the 3 rd , and two in the 4 th quartile. There were no nonimpact factor journals in this list. Most of the journals belonged to the United States of America (6) and England (3), while only one was published in Switzerland.
This table lists the top journals on silver diamine fluoride between 1969 and 2021. It also shows the journal's impact factor (IF), its quartile (Q), and publisher. The country of origin is given in the last column.
3.6. Bibliographic Coupling of Journals. Network graphs enable visualization of the bibliographic coupling of journals. These graphs usually consist of edges (the connections, here, they represent the publications), nodes (the entities, here, they represent the journals), and arrows that show the directed network type (in our case, all networks were directed and based on referrals). The size and color of the nodes (journals) and arrows depend on the data associated with them. Subject matter commonality among journals is measured by the bibliographic coupling of journals. Journals are bibliographically coupled if they refer to a common third 3.7. Major Themes in Silver Diamine Fluoride. Table 5 lists the twenty-five themes found in SDF research. 590 publications have been classified under the 25 themes. They had received a total of 10991 citations. SDF emerged as the top theme with 145 publications and 1785 citations (12.31 average citations per publication (C/P), followed by dental caries with 74 publications and 1447citations with 19.55 C/P. The 3 major themes that emerged in the selected 3 time periods were as follows:   (12), dental caries (7), dentine (6) P2 ( Figure 4 depicts the keyword co-occurrences in SDF research. Keywords that had a minimum of 12 cooccurrences or more were included. 22 keywords met this criterion. Figure 4 shows that the top five keywords were silver diamine fluoride, dental caries, caries, fluoride, and children with 147, 74, 39, 36, and 19 weights of occurrences, respectively. Keywords (demineralization, dentin, glass ionomer cement, and preventive dentistry) showed minimal cooccurrences (12) in this group. Closely related keywords were then classified into four clusters, and quantitative network indicators were used to describe the connections between those clusters. Silver diamine fluoride (the keyword with the highest occurrences) can be seen in cluster 4 along with children, primary teeth, caries arrest, early childhood caries, and sodium fluoride.
3.9. Bibliographic Coupling of Countries. Countries can be seen grouped into four clusters based on their close relations in content and connections as described by using quantitative network indicators. The United States of America, the country with the highest research output on SDF (Table 2), can be seen in cluster 2 along with United Kingdom, Saudi Arabia, India, Brazil, and Australia. Germany is in cluster 4.  Figure 7 presents the cocitation network of authors in SDF research between 1969 and 2021. Authors with 115 or more citations were included; 17 authors meet the criterion. It shows that top five Authors are grouped into clusters, and quantitative network indicators connect these clusters. There are 3 total clusters of authors: cluster 1 (5 authors), 2 (6 authors), and 3 (6 authors).

Authorship Pattern.
In this study, the authorship patterns focused on the authors' characteristics and the degree of collaboration among authors involved in a specific publication under study. The total number of authors per document was calculated in the study. Figure 8 represents the results of the authorship pattern analysis. The top three authorship patterns were five authors (87 publications), three authors (75 publications), and four authors (73 publications). Only two documents with 10 authors each were found. However, there were 10 documents with more than 11 contributors. The highly cited documents with 1429, 1162, and 1129 citations were authored by 3, 5, and 4 authors, respectively. Figure 9 demonstrates the three field plot of the relationship among countries, keywords, and journals. It shows that five countries (USA, Hong Kong, Brazil, China, and Australia) had published SDF literature using four main keywords (silver diamine fluoride, dental caries, caries, and fluoride). Research on SDF originated from these countries using these keywords was published in the following journals and had a strong relationship: Australian Dental Journal, Caries Research, Journal of Dental Research, Journal of Dentistry, and pediatric dentistry.

Three Field Plot (Countries, Keywords, and Journals).
3.14. Thematic Evolution Map of Keywords. Figure 10 reveals the evolution of keywords in three different stages; 1969-2010, 2011-2015, and 2016-2021. It can be observed that during the 1969-2010 period, the SDF themes dental caries and flouride had a high number of citations. This shows that these two themes had a high impact during this period. During the 2011-2015 period, the permanent molars, flouride, dental caires, silver diamine flouride, and silver themes received much attention from the researchers in the field of SDF.
Lastly, the documents published during the 2016-2021 period received high citations for the caries, silver, silver diamine flouride, and dental caries themes. On the other hand, themes such as tooth and oral health did not garner much attention during this period.

Discussion
This bibliometric analysis is the first of its kind as it aimed to identify and quantitatively evaluate the scientific research   claimed that SDF was effective in arresting dentine caries of primary teeth in preschool children. The trend of publishing on SDF has been slowly growing and has seen exponential growth after the year 2014.

Leading Countries and Institutions.
The results of the analysis have highlighted that the United States of America (USA), Hong Kong, and Japan were the top three most productive countries, with the USA having the highest number of publications and citations. This could be attributed to the existence of the National Institute of Dental and Craniofacial Research (NIDCR) in the USA which actively provides funding to both private and public sectors for dental research. Hong Kong had the second largest number of publications and citations after the United States of America. As for the most productive organizations, the University of Hong Kong led the way followed by the University of Washington, Seattle, and Tokyo Medical and Dental University, Japan. The Indonesian University was also amongst the top 10 most productive organizations, highlighting the promotion of research in this domain among the South East Asian countries. Furthermore, the domination of Hong Kong in the most productive countries and institution lists could be attributed to the presence of several different research clusters in the same institution having a similar field of interest [22][23][24]. Consequently, 5 of the top 10 highly cited authors, namely, Mei [22], Chu [24], and Lo [23], and Burrow M [25], were affiliated with The University of Hong Kong.

Leading Journals and Bibliographic Coupling of Journals.
Three out of the top 10 journals were enlisted in the Q1 ranking of the Web of Science database. These were equally distributed in between Elsevier (England), Sage (USA), and the American Dental Association (USA). The highly cited papers by Chu et al. [24] and Rosenblatt et al. [4] were both published in the Journal of Dental Research (Q1) by Sage Publishing Inc. (USA). Interestingly, all of the top 10 journals have been published either in England, the United States of America, or Switzerland. This is indicative of the trend that the developed countries have been making significant contributions within this field of research. Furthermore, they publish manuscripts in the English Language only, as were the records selected in our study.

Major Themes in SDF.
The systemic analysis also revealed the major themes in SDF research and the prevalent trends in publications on this specialty. Keywords aided researchers in conducting a targeted search for the relevant articles related to SDF in this study. The analysis of the more frequently used keywords helps investigators to target published research articles using the correct terms. The findings of the analysis showed that silver diamine fluoride (2011-2021) was a frequently used keyword in the last decade alongside dental caries (1969-2021) which has been used since the very beginning. This could be attributed to the fact that the Food and Drug Administration (FDA) approved the use of SDF for treating caries in 2014 and granted it breakthrough therapy status to treat severe early childhood caries in 2016 [26]. A similar trend was observed in the analysis of the number of publications, citations, and research collaboration. It should be noted that there have been reports of discoloration of dentition associated with the use of SDF, and alternative formulations are now readily available with potassium iodide which help with the reduction in the discoloration [27][28][29]. Dental caries has been the most commonly used keyword from 1969 to 2021, most likely due to the common application of SDF in different carious lesions in teeth, i.e, in enamel, dentine, or root caries [30].

Keyword Co-Occurrences in SDF.
The keywords had a specific trend among the publication chosen for analysis. As a rule, keyword co-occurrence networks are based on extracted keywords from the titles and abstracts of publications or even from the author generated keyword list. Keywords are said to co-occur if they both occur in the same title/abstract or citation context. Moreover, the distance between them is almost inversely proportional to the similarity of the keywords. Therefore, keywords with a higher rate of relevance are generally found to be closer to each other [31]. It was found that SDF, Caries, Fluoride, Remineralization, and Silver Fluoride have been the frequently used keywords. However, keywords related to staining were noticeably absent. In addition, the use of antistaining agents such as potassium iodide has not been highlighted in keywords so far [32,33].

Bibliographic Coupling of Countries and Authors.
The bibliographic coupling analysis is done to help reveal how a single item of reference is shared between two documents [34]. This analysis, when performed for countries, revealed    [7,35], have been identified as major contributors in research collaborations. This field of research appears to have been dominated by this cluster so far, and we would likely see more collaborative projects in the future from this cluster.

Authorship Pattern, Three Field Plots, and Thematic
Evaluation Maps of Keywords. The findings in this study showed that the trend of publications had a strong link with the selection of keywords. It is important to use relevant and appropriate keywords which can be easily searched, keeping in mind that different groups of readers may use various terms to describe the same information. The three-factor relationship showed that "silver diamine fluoride" and "dental caries" keywords were mainly used by authors from the USA, Brazil, Hong Kong, China, Australia, Japan, Saudi Arabia, and Germany. Interestingly, the keyword "dental caries" is a somewhat generic term while "silver diamine fluoride" is a very specific term related to the topic. The term "silver fluoride" was mainly seen in publications originating from Australia which had been mainly published in the Australian Dental Journal. It was also observed that studies originating from the USA had been published in different journals, with the majority being published in Pediatric Dentistry (the official publication of the American Academy of Pediatric Dentistry), the Journal of Dental Research, the American Journal of Dentistry, and the Journal of the American Dental Association. On the other hand, most British researchers had mainly published in the British Dental Journal and BMC Oral Health. This particular trend shows that the researchers tended to focus on journals being published in their own respective countries. Furthermore, it was noted that the term "silver diamine fluoride" was also used in articles from Japan, China, the USA, Brazil, and Hong Kong but not in those from Australia. Keywords associated with the methods of application of SDF and its properties such as "antibacterial" and "remineralization" were used less frequently.
In the thematic evaluation of the data, it was found that keywords such as "dental caries," "silver fluoride," and "fluoride" have been used throughout the last 52 years. Similarly, "silver fluoride" has been used frequently during the 1969-2010 period. However, the term "sliver diamine fluoride" has only been used since 2011, and in the last five years, it has been used along with keywords "caries" and "prevention." The use of the keyword "silver diamine fluoride" after 2011 might be due to its approval as a Class II medical device for the treatment of dental hypersensitivity by the US Food and Drug Administration. In 2009, WHO classified SDF as an "effective, efficient, equitable and safe cariespreventative agent" [4]. However, the term "dental hypersensitivity" was not a commonly used keyword in this study.
The results of this study highlight that there has been significant variation in terms of the nature and size of the collaborating teams in SDF research. The analysis of the authorship pattern and network structure confirmed that a high number of publications had multiple authors (3, 4, or 5). This can be related to the frequent collaborations among various institutes, countries, and researchers to expedite the development of this area of research. Notably, a very high number of authors (10 or 11) had a very low number of publications. It could be because nowadays most journals discourage a high number of authors (more than 6) per publication to circumvent the trend of guest authorship.

Limitations and Future Research
Directions. This study was limited by the use of a single database for the collection of bibliographic data. Other databases such as the Web of Science, PubMed, and Google Scholar were not taken into account. Furthermore, the factor of self-citation was not analyzed as there is currently no methodology available to do so. Regardless of its limitations, this study on silver diamine fluoride could aid future investigators in identifying possible avenues for research and filling the identified gaps in research. Also, it would help them identify the most influential countries, universities, authors, journals, and keywords while researching the topic and looking for collaborations.
Future areas of interest for researchers could include expansion of the search to other databases, investigating the use of nanosilver sodium fluoride [38] in dentistry and its clinical applications as compared to SDF, the staining potential of SDF, and novel formulations that can minimize or neutralize the staining caused by SDF.

Conclusions
This bibliometric analysis provides valuable information on the total number of publications on SDF and their citation 11 BioMed Research International details during the 1969 to 2021 period. It has shown that there was an overall upward trend in publishing on the topic with a significant increase in the number of publications after 2014. It has also identified the leading countries and organizations involved in the research on SDF and the research trends related to it. Even though the use of silver diamine fluoride has become prevalent in the last few decades, only the last few years have seen significant scientific publications. It is hoped that this study would allow budding and existing researchers to imagine and build future scenarios for scientific collaborations for research on the use of SDF in dentistry.

Disclosure
The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.