Journal of Cutaneous and Aesthetic Surgery

ORIGINAL ARTICLE
Year
: 2020  |  Volume : 13  |  Issue : 2  |  Page : 95--102

Global trends of botulinum toxin literature: A bibliometric analysis of botulinum toxin publications between 1975 and 2017


Engin Senel1, Ümran Muslu2,  
1 Department of Dermatology and Venerology, Hitit University Faculty of Medicine, Çorum, Turkey; Traditional and Complementary Medicine Application and Research Center, Hitit University, Çorum, Turkey; Beekeeping and Bee Products Application and Research Center, Hitit University, Çorum, Turkey
2 Traditional and Complementary Medicine Application and Research Center, Hitit University, Çorum, Turkey; Department of Plastic and Reconstructive Surgery, Hitit University Faculty of Medicine, Çorum, Turkey

Correspondence Address:
Engin Senel
Department of Dermatology and Venereology, Hitit University Faculty of Medicine, Çorum 19200.
Turkey

Abstract

Background: Botulinum toxin has been effectively used cosmetically and therapeutically for the last decades in a wide range of medical conditions. Although bibliometrics has been a popular and growing study area in recent years, medical literature lacks studies evaluating published botulinum toxin literature. Objective: The goal of our study was to evaluate bibliometric features and to perform a detailed trend analysis in the medical literature related to botulinum toxin. Materials and Methods: We analyzed all the published documents including the keywords “botulinum toxin” and “botulinum neurotoxin” and commercial brand names of botulinum toxin products between 1975 and 2017. We performed a detailed bibliometric and scientometric assessment in this field. Results: A total of 24,948 articles were retrieved from four databases provided by Web of Science, and most of which were original articles (76.19%). The United States ranked first and dominated literature with 8,729 documents (34.29%) followed by the United Kingdom, Germany, and Italy (14.61%, 11.18%, and 5.5%, respectively). The United Kingdom was detected to be the most productive country with the highest productivity (55.09) followed Switzerland, Denmark, and Germany (47.7, 34.01, and 33.98, respectively). The most studied area was neurology (56.1%) and University of California System was the most productive institution. We noted no correlation between publication number and citations by year. Conclusion: We found that all top 10 authors and institutions were from developed countries. Physician from developing and the least-developed countries should be supported to carry out novel studies on botulinum toxin.



How to cite this article:
Senel E, Muslu &. Global trends of botulinum toxin literature: A bibliometric analysis of botulinum toxin publications between 1975 and 2017.J Cutan Aesthet Surg 2020;13:95-102


How to cite this URL:
Senel E, Muslu &. Global trends of botulinum toxin literature: A bibliometric analysis of botulinum toxin publications between 1975 and 2017. J Cutan Aesthet Surg [serial online] 2020 [cited 2020 Jul 6 ];13:95-102
Available from: http://www.jcasonline.com/text.asp?2020/13/2/95/287308


Full Text



 Introduction



Botulinum neurotoxin (BoNT) as the most potent biological toxin has been effectively used both therapeutically and cosmetically for a wide range of disorders in various of medical conditions.[1] Bibliometrics is the evaluation of scientific literature in a certain field in an all-inclusive manner.[2] Although there has been a rising popularity of bibliometric and scientometric assessment of the scientific data, the medical literature lacks a study investigating bibliometric features of the articles related to BoNT. In this study, we aimed to perform a detailed bibliometric evaluation of botulinum toxin literature and generated a trend analysis in this popular area.

 Subjects and Methods



All the documents published between 1975 and 2017 including “botulinum toxin” and “botulinum neurotoxin,” and commercial brand names of BoNT products such as “botox,” “dysport,” and “xeomin” were analyzed in this study. All data used in our study were retrieved from four databases (Web of Science Core Collection, Russian Science Citation Index, SciELO Citation Index, and Korean Journal Database) provided by Web of Science (WoS) (Thomson Reuters, New York). All articles published in 2018 were excluded. Articles published from Wales, England, Scotland, and Northern Ireland were evaluated under the United Kingdom main title. The “China” main heading was used for the articles from People’s Republic of China and the mainland of China. Documents from Germany, West Germany, East Germany, and Federal Republic of Germany were united under “Germany” main heading. We performed statistical analyses using SPSS (version 22.0, SPSS Inc., Chicago, IL; licensed for Hitit University, Çorum, Turkey). Spearman’s correlation coefficient analysis was used to investigate a possible correlation between publication numbers and citations of the literature. A value of P < 0.05 was accepted as statistically significant. We created infographics revealing world distribution density of botulinum toxin literature using GunnMap free software and Microsoft Excel (Microsoft Corporation, Redmond, Washington).[3] We created bibliometric network maps showing the most used keywords, and relationships and connection of the countries and the institutions. Bibliometric network visualization maps were generated by using VOSviewer resource freeware (Centre for Science and Technology Studies, Leiden University, Leiden, The Netherlands) in our study.[4]

 Results



Total number of publications

As we searched four databases, a total of 24,948 documents were found and 82.43% of which was in the WoS Core Collection. It was noted that 5,688 items were open access. Most of the documents were original articles (n = 19,009; 76.19%). Other most published document types were abstracts, reviews, and meeting reports (17.88%, 17.44%, and 14.4%, respectively) [Table 1]. The United States was the leading country in the literature with 8,729 items (34.29%) followed by the United Kingdom, Germany, and Italy (14.61%, 11.18%, and 5.5%, respectively) [Figure 1]. All top 10 countries ranked by total publication number were developed countries [Figure 2].{Table 1}, {Figure 1}, {Figure 2}

Productivity

We calculated a productivity score for each country publishing academic documents. We measured the score with a formula published previously in the literature (total production number of country/population × 1,000,000). The United Kingdom ranked first with the highest productivity score (55.09) followed by Switzerland, Denmark, and Germany (47.7, 34.01, and 33.98, respectively). The United States which ranked 1 in literature (34.29%) with the total publication number was 8 in this ranking [Figure 3].{Figure 3}

Research areas, authors, journals, and institutions

Neurology, pharmacology, and biochemistry were found to be the most studied areas in the literature related to BoNT (56.51%, 56.12%, and 47.16%) [Table 2]. Aktories was detected to be the most productive author with 235 articles (0.94%) followed by Jankovic and Dressler (0.69% and 0.65%) [Table 3]. All top 10 authors were from developed countries. University of California System was noted to be the most productive institution with 708 items (3%). All institutions were from developed countries [Table 4]. Movement Disorders was the leading journal in botulinum toxin literature and covered 3.34% of all documents followed by Neurology and Toxicon (2.08% and 1.99%, respectively) [Table 5].{Table 2}, {Table 3}, {Table 4}, {Table 5}

Progression of publications and citations and the correlations

We performed a citation analysis of the last decade of BoNT literature. In the last decade, a total of 9,555 articles were published in this field. H-index of botulinum toxin literature was measured to be 83. Documents published in BoNT literature were cited 83,376 times (48,233 times without self-citations) in total between 2008 and 2017. Average citations per item was measured to 8.73 times. Peak year for citations was 2017 (n = 17,496) [Figure 4]. We detected no correlation between publication number and citation number by year (P = 0.232). The most cited article in this field was found to be titled “Recommendations for the pharmacological management of neuropathic pain: an overview and literature update” by Dworkin et al.[5] published in Mayo Clinic Proceedings cited 592 times (average citations per year: 65.78) [Table 6].{Figure 4}, {Table 6}

Bibliometric network analyses

As we performed a detailed keyword analysis, we found that the most used keywords in this field were “botulinum toxin,” “botulinum toxin type a,” “spasticity,” and “dystonia.” We noted that the most used keywords were selected from neurological terms. We generated a bibliometric keyword network visualization map in which the keyword of “botulinum toxin” centered with the largest diameter and connected with the other keywords [Figure 5]. We created a connection network map of the countries producing documents in this area, and this bibliometric network revealed seven main centers including the United States, Germany, United Kingdom, Italy, Canada, France, and Japan. Institutional bibliometric network showed connections between medical organizations and the companies producing commercial BoNT products [Figure 6].{Figure 5}, {Figure 6}

Indian contribution to the literature

Although Indian population is equivalent to 17.71% of the total world population, it produced only 0.83% of all botulinum toxin literature (n = 207 articles). The most common document type was original article (64.368%) followed by review, letter, and meeting abstract (21.839%, 5.747%, and 4.598%, respectively). The most prolific Indian author was Dhaked from Biotechnology Division, Defence Research and Development Establishment, with 10 articles. Defence Research and Development Establishment was also the most productive institution of the Indian literature with 17 documents. Annals of Indian Academy of Neurology was the most productive source title with seven items. H-index of Indian literature was measured as 20 and total number of citations was 1760 (1719 without self-citations). The most cited manuscript was a review titled “Drooling in Parkinson’s disease: a review” written by Srivanitchapoom et al.[6] published in 2014. This article has been cited 123 times in total.

 Discussion



Botulinum toxin serotypes inhibit neurotransmitter release from nerve terminals and prevent acetylcholine release at the neuromuscular junction. Seven different types of BoNT titled from BoNT A through BoNT G have been identified so far. An eighth serotype named BoNT X has been reported more recently but no product of this serotype has been produced yet.[7] Although Clostridium botulinum is the organism for the production of BoNT, some companies have been exploring the use of recombinant expression of Escherichia coli.[8] Generated infographic of institutional bibliometric map revealed a cooperative network of the companies producing publications in BoNT literature [Figure 6].

Bibliometrics is a novel and popular scientific field investigating academic literature and analyzing publication trends and patterns in a certain area.[9] Although an expanding and high demand across the world has been reported in noninvasive cosmetic treatment solutions such as botulinum toxin, to the best of our knowledge, there has been no study investigating bibliometric features of botulinum toxin literature.[10] Thus, the only limitation of our article was that there was no study to compare our results within the literature.

Today, the cosmetic use of BoNT has been reported to be the most common aesthetic procedure performed throughout the world.[11] Current common aesthetic applications of BoNT include treatment of forehead wrinkles and glabellar, periorbital, perioral, and horizontal neck lines. In 2015, the members of American Society of Dermatologic Surgery (ASDS) performed approximately 10 million treatments and BoNT A was used in 1.8 million of which. The net revenue of BoNT A application in aesthetic indications reached $199.4 million in 2016 and according to the American Society of Plastic Surgeons, a total of 15.4 million aesthetic procedures were performed during 2016 and in 7 million of which BoNT A was used.[12] According to 2017 report of ASDS, nearly 12 million cosmetic procedures were performed and BoNT A was applied in 2.1 million of which.[13] In the United States, three BoNT A formulations are available for aesthetic applications although specific aesthetic versions of BoNT A are on market in the European Union. BoNT B is also available for neurological conditions and it is not yet approved for aesthetic indications.[14],[15] Use of BoNT A has been rising for the last decades cosmetically and therapeutically, and the global market for BoNT A is estimated to reach approximately $7.4 billion by 2024.[10] Although the products of botulinum toxin are known to have been used only cosmetically and aesthetically, we found that the most searched area in BoNT literature is neuroscience. However, we noted that BoNT A has been studied much more than BoNT B and even BoNT B was not one of the most common 20 keywords [Figure 5]. We detected that all authors and institutions in the top 10 productive lists were from developed countries. The United States was reported to represent the largest market worldwide, and we found that US Department of Defense and US Army were in top 10 institutions reporting researches investigating botulinum toxin (1.76 and 1.57, relatively) [Table 4] supported by approvals for the application in novel therapeutic indications.[10]

Although the dose units are specific for each BoNT A product family, we detected that differences of BoNT A products were not included in the most studied areas, and the brand names of BoNT A were not in the most used keywords list [Figure 5].

 Conclusions



Botulinum toxin has been reported to be the most poisonous substance known and it can be used as a biological weapon. Even a single gram toxin of a crystalline toxin inhaled would kill more than one million people.[16],[17] Therefore, more studies investigating botulinum toxin and bioterrorism should be carried out. We suggest that researchers from developing and least-developed countries should be funded and encouraged to perform novel studies, particularly on BoNT B.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Tinastepe N, Küçük BB, Oral K. Botulinum toxin for the treatment of bruxism. Cranio 2015;33:291-8.
2Hood WW, Wilson CS. The literature of bibliometrics, scientometrics, and informetrics. Budapest Sci 2001;52:291-314.
3GunnMap. GunnMap 2 Available at: http://lert.co.nz/map/.
4van Eck NJ, Waltman L. VOSviewer—Visualizing scientific landscapes. Leiden, The Netherlands: Centre for Science and Technology Studies, Leiden University; 2017.
5Dworkin RH, O’Connor AB, Audette J, Baron R, Gourlay GK, Haanpää ML, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010;85(Suppl 3):S3–S14.
6Srivanitchapoom P, Pandey S, Hallett M. Drooling in Parkinson’s disease: a review. Parkinsonism Relat Disord 2014;20:1109-18.
7Zhang S, Masuyer G, Zhang J, Shen Y, Lundin D, Henriksson L, et al. Identification and characterization of a novel botulinum neurotoxin. Nat Commun 2017;8:14130, 1-10.
8Fonfria E, Maignel J, Lezmi S, Martin V, Splevins A, Shubber S, et al. The expanding therapeutic utility of botulinum neurotoxins. Toxins (Basel) 2018;10:208.
9Şenel E, Demir E, Alkan RM. Bibliometric analysis on global Behçet disease publications during 1980–2014: is there a Silk Road in the literature? J Eur Acad Dermatol Venereol 2017;31: 518-22.
10Global Industry Analysts. Rising demand for minimally invasive cosmetic treatments and expanding therapeutic indications fuel growth in the botulinum toxin market. 2018. Available at: https://www.strategyr.com/MarketResearch/market-report-infographic-botulinum-toxin-forecasts-global-industry-analysts-inc.asp.
11Dorizas A, Krueger N, Sadick NS. Aesthetic uses of the botulinum toxin. Dermatol Clin 2014;32:23-36.
12Dover JS, Monheit G, Greener M, Pickett A. Botulinum toxin in aesthetic medicine: myths and realities. Dermatol Surg 2018;44:249-60.
13American Society of Dermatologic Surgery. ASDS Survey on Dermatologic Procedures. Available at: https://www.asds.net/medical-professionals/practice-resources/asds-survey-on-dermatologic-procedures.
14Maas C, Kane MA, Bucay VW, Allen S, Applebaum DJ, Baumann L, et al. Current aesthetic use of abobotulinumtoxinA in clinical practice: an evidence-based consensus review. Aesthet Surg J 2012;32:8S-29S.
15Kamin W, Staubach P, Klär-Hlawatsch B, Erdnüss F, Knuf M. [Anaphylaxis after vaccination due to hypersensitivity to gelatin]. Klin Padiatr 2006;218:92-4.
16Gill DM. Bacterial toxins: a table of lethal amounts. Microbiol Rev 1982;46:86-94.
17Arnon SS, Schechter R, Inglesby TV, Henderson DA, Bartlett JG, Ascher MS, et al. Botulinum toxin as a biological weapon: medical and public health management. JAMA 2001;285:1059-70.