Sage Journals: Discover world-class research

Abstract

Purpose:

The main objective of this study was to examine the publication pattern of N-acetylcysteine (NAC) research output for paracetamol overdose at the global level.

Methods:

Data were searched for documents that contained specific words regarding NAC and paracetamol as keywords in the title and/or abstract and/or keywords. Scientific output was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product per capita.

Results:

The criteria were met by 367 publications from 33 countries. The highest number of articles associated with the use of NAC in paracetamol overdose was from the United States of America (USA; 39.78%), followed by the United Kingdom (UK; 11.99%). After adjusting for economy and population power, USA (2.822), Iran (1.784) and UK (1.125) had the highest research productivity. The total number of citations at the time of data analysis (14 March 2014) was 8785 with an average of 23.9 citations per document and a median (interquartile range) of 6 (1–22). The h-index of the retrieved documents was 48. The highest h-index was 32 for USA, followed by 20 for UK. Furthermore, the highest number of collaborations with international authors for each country was held by USA with 11 countries, followed by Canada with 7 countries.

Conclusion:

The amount of NAC-based research activity was low in some countries, and more effort is needed to bridge this gap and to promote better evaluation of NAC use worldwide. Our findings demonstrate that NAC use for paracetamol overdose remains a hot issue in scientific research and may have a larger audience compared with other toxicological aspects. Editors and authors in the field of toxicology might usefully promote the submission of work on NAC in future to improve their journal’s impact.

Keywords

Bibliometric acetylcysteine NAC paracetamol acetaminophen poisoning citations

Introduction

Initially, N-acetylcysteine (NAC) was used via inhalation as a mucolytic drug. Currently, NAC is administered orally or intravenously (IV) for the treatment of paracetamol overdose.¹ In 1974, Mitchell and colleagues reported that increasing glutathione level in the liver could be achieved through administration of NAC and therefore could help in preventing paracetamol – induced hepatotoxicity.² Also in 1974, the work by Prescott et al. demonstrated that NAC was an effective antidote in patients who presented to hospital after paracetamol poisoning.³ The United States Food and Drug Administration approved the use of oral NAC preparations in 1985 and IV-NAC preparations in 2004. IV-NAC is now the standard treatment for paracetamol poisoning in the United Kingdom (UK) and the United States of America (USA), and also in Asia, Australia, Canada and Europe.⁴

The evolution of scientific output in the field of toxicology has been poorly explored to date and there are few internationally published reports on research activity in toxicology.^{5

–13} Paracetamol also maintains substantial interest among researchers, as demonstrated by the continuous growth of scientific literature. During the past years, publications involving paracetamol have increased 60 times.^13,14 It is interesting to note that publications in general medical field have only increased threefold. To the best of our knowledge, there is a lack of data concerning the evaluation of scientific research productivity of NAC use in paracetamol overdose worldwide. Scientific progress is one of the most important indicators for the community and economic development of different countries.¹⁵ There are several well-known databases, including PubMed, Scopus, Web of Science (i.e. Thomson Reuters Institute for Scientific Information (ISI)) and Google Scholar, for indexing international publications in biomedical sciences.¹⁶ The evaluation of scientific research is an essential task where the purpose of evaluation is to determine – and, where possible, improve – its productivity. Given that the outcome of scientific activity is only known when the authors communicate their findings in a publication distributed among the scientific community, bibliometric indicators are of great importance.¹⁷ Bibliometric analysis is a useful tool to obtain a clear picture of the current state of scientific research and, in particular, areas that allow researchers to recognize and undertake new lines of research.¹⁸ This type of analysis utilizes quantitative analysis and statistics to obtain the bibliographical works within a given field, topic, institution or country.^19
–21 This study will lead to a better understanding of the current and future status of research related to NAC use for paracetamol overdose worldwide.

The aims of this study were: (1) to examine the publication pattern of NAC research output at the global level; (2) to analyse the publication pattern and impact of the most productive countries; (3) to analyse the collaborative patterns among the top 10 most productive countries; (4) to examine the productivity and impact of the most prolific institutions; (5) to examine the productivity and impact of the most prolific authors; (6) to examine the impact of the most preferred journals; and (7) to identify the highly cited papers.

Methods

Search strategy

The data used in this study were based on the Scopus online database. A comprehensive online search was performed using SciVerse Scopus, which is one of the world’s largest databases of peer-reviewed literature. Scopus covers nearly 18,000 titles from 5000 publishers worldwide, contains 41 million records and provides 100% coverage of MEDLINE.²² Elsevier, combining the characteristics of both the Web of Science and PubMed, developed the Scopus database. These characteristics allow for an enhanced service for educational and academic needs as well as for medical literature research and bibliometric analysis. Scopus offers basic search and advanced search features. In the basic search, the results for the chosen keywords can be limited by the date of publication, subject area or document type.^11,16,23

The keywords entered into the Scopus search engine to achieve the objectives of this study were ‘acetylcysteine’, ‘N-acetyl-l-cysteine’ or ‘NAC’ as part of the ‘Article Title’. Most of the time, the term ‘acetylcysteine’, which is used for several indications, was not related to paracetamol overdose. To avoid this, keywords related to paracetamol (‘acetaminophen’, ‘paracetamol’, ‘tylenol’ and ‘APAP’) were entered as part of the ‘Article Title’ or ‘Abstract’ or ‘Keywords’. All subject areas were selected for this search, namely, health sciences, social sciences, life sciences and physical sciences, including all previous years up to 31 December 2012. We excluded documents that were published as an erratum or not related to paracetamol overdose. Scientific research productivity in the years 2013 and 2014 was excluded because these years were still open for new journal issues and therefore inclusion of the year 2013 would create error and bias. All searches were completed on 14 March 2014 to avoid bias due to the daily updating of the database.

The collected data were used to generate the following information: (a) total and trends of contributions in NAC research during all previous years up to 31 December 2012; (b) research productivity and collaboration patterns by country; (c) type of the articles (e.g. editorial, review article, original article, brief communication and case letter to the editor); (d) journals in which international researchers published; (e) the productivity and impact of the most prolific authors and institutions; and (f) the citations received by the publications.

Indices of research productivity

Scientific output was evaluated based on a methodology developed and used in other bibliometric studies.^11,14,24,25 The measurements of bibliometric analysis (e.g. countries, cited articles and institutions) were converted to the rank order using the standard competition ranking. We took in our consideration only the 10 top ranks. If the measurements of bibliometric analysis have the same ranking number, then a gap is left in the following ranking numbers. The h-index for data collected from Scopus is presented. The h-index is a country’s number of articles (h) that have received at least h citations. It quantifies both country-scientific productivity and scientific impact and it is also applicable to scientists, journals, and so on.²⁶ That is to say, a country with an h-index of 10 has published 10 documents, each has attracted at least 10 citations. Documents with fewer than 10 citations are not calculated by the index. The h-index was originally developed as a way of qualifying research performance.²⁷ Two common performance indicators were considered for the top 10 ranked journals using data from the most recent year available.²⁸ First, the journal impact factor (IF) was evaluated using the Journal Citation Report (Web of Knowledge) 2012 science edition by Thomson Reuters (New York, USA). The second measure of journal performance used in this study was the SCImago Journal Rank (SJR) indicator. A detailed explanation on how the SJR calculation is made can be found on the SCImago website (available at: http://www.scimagojr.com/SCImagoJournalRank.pdf, accessed 29 March 2014). Publication activity was adjusted for the top 10 countries, categorized by population size and gross domestic product (GDP), which were retrieved from the online databases of the World Bank.²⁹ An adjustment index (AI) was calculated using the following formula: $A I = [total number of publications for the country / GDP per capita of the country] \times 1000$ , where the GDP per capita = GDP/population of the country.^11,30

Ethical approval

The institutional review board (IRB) at An-Najah National University does not require submission of an IRB application for a bibliometric study. The IRB confirmed that there is no risk to human subjects in this type of research since the data are based on published literature and, as secondary data, did not involve any interactions with human subjects.

Statistical analysis

Data from Scopus were exported to Microsoft Excel^® and then transferred to the Statistical Package for Social Sciences (SPSS; Version 15, SPSS Inc, Chicago, Illinois, USA) program for analysis. Variables that were not normally distributed, such as the number of citations, are expressed as a median (Q1–Q3: interquartile range). Categorical data are expressed as numbers with percentages. Pearson’s correlation analysis was used to examine the association between research productivity and country variables. Reliability and validity are important for conducting a pilot study in this method. Inter-method reliability assesses the variation in measurements of the same target when made by different methods or instruments but by the same person.^31
–33 Depending on the variables’ level of measurement, an intraclass correlation coefficient can statistically determine the reliability for numerical variables. It is recommended that more than 95% reliability should be achieved for important variables.^31

–35 Intraclass correlation coefficient was calculated to determine the inter-method variability using SPSS.^31,36 To assess the reliability of our method, we compared two different methods of data collection. In the first one, we used data extraction, whilst in the second one, all publications related to each author in the top 10 lists were extracted and reviewed. The intraclass correlation coefficient value between the two methods was 0.98. There was an excellent agreement between the two methods, indicating that our method was valid.

Results

Type of documents

Using the methodology stated above, 367 documents were retrieved comprising 230 (62.7%) original journal articles, 46 (12.5%) letters to the editor, 34 (9.3%) review articles and 57 (15.5%) other types of publication such as notes or editorials. The language in which the documents were published was dominated by English (n = 338, 92.1%), followed distantly by German (n = 19), Dutch (n = 22) and French (n = 7).

Annual research productivity

The annual number of documents published between 1976 and 2012 indicated that research output was low in the first two decades but showed an obvious increase in the last years (Figure 1). The annual distribution of documents showed a non-linear growth rate, with a publication peak between 2008 and 2011. There was a moderately positive but statistically significant correlation between time and number of publications (r = 0.62, p < 0.001) between 1976 and 2012. The first article related to NAC in Scopus was published by Piperno and Berssenbruegge in The Lancet in 1976.³⁷

Figure 1.

Total articles included in a bibliometric analysis of worldwide publications related to NAC use for paracetamol overdose from 1976 to 2012. NAC: N-acetylcysteine.

Research productivity and collaboration stratified by country

In total, documents were published in 33 countries. Table 1 shows the ranking list of the 10 countries whose researchers published the largest number of articles related to NAC use in paracetamol overdose during the period from 1976 to 2012. When the data were analysed by country, the largest number of articles was from USA (39.78%), followed by UK (11.99%) (Table 1). After adjusting for economy and population power, USA (2.822), Iran (1.784) and UK (1.125) had the highest research productivity (Table 1). Number of publications in each country was compared with country variables such as population and GDP. There was a strong correlation between the number of published articles related to NAC use in paracetamol overdose and the population size in millions (r = 0.92, p < 0.001). There was also a strong correlation between the number of publications of each country and its GDP (r = 0.96, p < 0.001).

Table 1.

Research productivity, collaboration and citation analysis stratified by country and presented as top 10 ranking.

SCR^a	Country	Articles (%)	h-Index	Median (Q1–Q3) of citation	Citation average	Collaborations with foreign countries	Number of documents with international authors	Publications per population size in million	AI^b
1st	USA	146 (39.78)	32	10 (2–29)	30.6	6	11	0.47	2.822
2nd	UK	44 (11.99)	20	13 (2.8–49.5)	49.5	2	2	0.70	1.125
3rd	Canada	25 (6.81)	13	15 (6.5–32)	38.4	2	7	0.72	0.479
4th	Australia	15 (4.09)	8	12 (4–63)	30.8	1	1	0.66	0.222
5th	Iran	12 (3.27)	7	10.5 (3–21.3)	17.1	0	0	0.16	1.784
6th	Denmark	10 (2.72)	5	5 (2.8–31)	15.1	0	0	1.79	0.178
7th	Germany	9 (2.45)	3	2 (0.5–22.5)	27.3	3	4	0.11	0.215
7th	Turkey	9 (2.45)	4	0 (0–17)	12.1	0	0	0.12	0.844
9th	France	8 (2.18)	3	2 (0.2–4)	3	1	1	0.12	0.201
9th	Israel	8 (2.18)	5	14 (2.5–26.5)	16.4	0	0	1.01	0.245

SCR: standard competition ranking; USA: United States of America; UK: United Kingdom; Q1–Q3: lower quartile – upper quartile; AI: adjustment index.

^aEqual countries have the same ranking number and then a gap is left in the ranking numbers.

^bAn AI was calculated using the following formula: $A I = [t o t a l n u m b e r o f p u b l i c a t i o n s f o r t h e c o u n t r y / G D P p e r c a p i t a o f t h e c o u n t r y] \times 1000$ , where GDP per capita = GDP/population of the country.

The total number of citations at the time of data analysis (14 March 2014) was 8785 with an average of 23.9 citations per document and a median (interquartile range) of 6 (1–22). The highest median (interquartile range) number of citations was 15 (6.5–32) for Canada and 14 (2.5–26.5) for Israel, followed by 13 (2.8–49.5) for UK. The h-index of the retrieved documents was 48 (i.e. 48 documents had been cited at least 48 times at the time of data analysis, 14 March 2013). The highest h-index was 32 for USA, followed by 20 for UK and 13 for Canada. Furthermore, the highest number of collaborations with international authors for each country was held by USA with 11 articles, followed by Canada with 7 articles (Table 1). There was a statistically significant and strong correlation between the number of country collaborations and the number of publications related to NAC use in paracetamol overdose for each country (r = 0.87, p = 0.001). However, there was no statistically significant correlation between the number of country collaborations and average number of citations (r = 0.48, p = 0.156).

Source title

The retrieved documents were published in 199 international peer-reviewed journals. Table 2 shows the ranking of the top 10 journals in which articles related to NAC use in paracetamol overdose from international authors were published. Thirty-one documents (8.46%) were published in Annals of Emergency Medicine, followed by 23 (6.27%) in Clinical Toxicology, whereas 19 (5.17%) were published in The Lancet, followed by 9 (2.45%) being published in each of British Medical Journal and Human and Experimental Toxicology. Five journals from the top 10 ranking journals had SJR <1. In Table 3, a list of the most cited articles from 1976 to 2012 is shown. The most cited research area in the list of the most cited articles related to NAC use in paracetamol overdose was ‘clinical study’ (8 articles of 10).

Table 2.

Ranking of the top 10 journals in which articles related to NAC use in paracetamol overdose were published worldwide with their IFs.

SCR^a	Journal	Frequency (%)	SJR	IF (2012)^b
1st	Annals of Emergency Medicine	31 (8.46)	1.4	4.285
2nd	Clinical Toxicology	23 (6.27)	0.64	2.592
3rd	Lancet	19 (5.17)	7.07	39.060
4th	British Medical Journal	9 (2.45)	1.48	17.215
4th	Human and Experimental Toxicology	9 (2.45)	0.42	1.453
6th	Journal of Pharmacology and Experimental Therapeutics	8 (2.18)	1.39	3.891
7th	Annals of Pharmacotherapy	7 (1.91)	0.82	2.567
8th	Journal of Toxicology Clinical Toxicology	6 (1.63)	0.64	2.592
8th	New England Journal of Medicine	6 (1.63)	10.16	51.658
8th	Toxicology	6 (1.63)	1.09	4.017
8th	Veterinary and Human Toxicology	6 (1.63)	N/A	N/A

SCR: standard competition ranking; SJR: SCImago Journal Rank; IF: impact factor; ISI: Institute for Scientific Information; JCR: journal citation reports; NAC: N-acetylcysteine; IF: impact factor.

^aEqual journals have the same ranking number, and then a gap is left in the ranking numbers.

^bThe IF was reported according to the ISI JCR 2012.

Table 3.

Top 10 ranking of cited articles related to NAC use in paracetamol overdose worldwide in Scopus.

SCR	Authors with year of publication	Title	Source title	Research area	Article type	Cited by
1st	Zafarullah et al. (2003)	Molecular mechanisms of N-acetylcysteine actions	Cellular and Molecular Life Sciences	Molecular biology	Review article	505
2nd	Smilkstein et al. (1988)	Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the National Multicenter Study (1976 to 1985)	New England Journal of Medicine	Clinical report	Original article	449
3rd	Harrison et al. (1991)	Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure	New England Journal of Medicine	Clinical report	Original article	309
4th	Prescott et al. (1979)	Intravenous N-acetylcysteine: The treatment of choice for paracetamol poisoning	British Medical Journal	Clinical report	Original article	302
5th	Kelly (1998)	Clinical applications of N-acetylcysteine	Alternative Medicine Review	Clinical report	Review article	263
6th	Keays et al. (1991)	Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: A prospective controlled trial	British Medical Journal	Clinical report	Original article	243
7th	Harrison et al. (1990)	Improved outcome of paracetamol-induced fulminant hepatic failure by late administration of acetylcysteine	Lancet	Clinical report	Original article	216
8th	Gillissen and Nowak (1998)	Characterization of N-acetylcysteine and ambroxol in anti-oxidant therapy	Respiratory Medicine	Molecular biology	Review article	195
9th	Rumack et al. (1981)	Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment	Archives of Internal Medicine	Clinical report	Original article	173
10th	Atkuri et al. (2007)	N-Acetylcysteine-a safe antidote for cysteine/glutathione deficiency	Current Opinion in Pharmacology	Clinical report	Review article	158

SCR: standard competition ranking; NAC: N-acetylcysteine.

Research productivity stratified by authors and institutions

Table 4 presents the top 10 ranking of prolific authors who published more articles related to NAC use in paracetamol overdose from the world, with their affiliations and publication patterns, those authors have published at least six articles during the period of study. The retrieved documents were published by 181 institutions. Table 5 shows the ranking of the top 10 most productive institutions that most frequently published articles related to NAC use in paracetamol overdose globally. The most productive institution was Rocky Mountain Poison and Drug Center, USA (3.27% of total publications), followed by Royal Infirmary of Edinburgh, UK (2.72%) and University of California, San Francisco, USA (1.91%).

Table 4.

The top 10 ranking of prolific authors who published more articles related to NAC use in paracetamol overdose from the world, 1976–2012, with their affiliations and publication patterns.

SCR^a	Author	Number (%)^b of publications	Affiliation
1st	Rumack BH	14 (3.8)	University of Colorado Health Sciences Center, Department of Pediatrics, Denver, USA
2nd	Peterson RG	10 (2.7)	Department of Pediatrics and Pharmacolgy, University of Ottawa, Children's Hosp. of Eastern Ontario, Ottawa, Ont. K1 H 8L1, Canada
3rd	Dalhoff K	9 (2.5)	Bispebjerg Hospital, Department of Clinical Pharmacology, Copenhagen, Denmark
3rd	Corcoran GB	9 (2.5)	Wayne State University, Department of Pharmaceutical Sciences, Detroit, USA
5th	Krenzelok EP	8 (2.2)	University of Pittsburgh Medical Center, Department of Pharmacy, Pittsburgh, USA
5th	Prescott LF	8 (2.2)	University of Edinburgh, Edinburgh, UK
7th	Dawson AH	7 (1.9)	University of Sydney, Central Clinical School, Sydney, Australia
7th	Racz WJ	7 (1.9)	Queen's University, Kingston, Department of Pharmacology and Toxicology, Kingston, Canada
7th	Bateman DN	7 (1.9)	Royal Infirmary of Edinburgh, Edinburgh, UK
10th	Klein-Schwartz W	6 (1.6)	University of Maryland School of Pharmacy, Department of Pharmacy Practice, Baltimore, USA
10th	Heard K	6 (1.6)	Rocky Mountain Poison and Drug Center, Denver, USA
10th	Dart RC	6 (1.6)	University of Colorado at Boulder, Denver School of Medicine, Boulder, USA
10th	Harrison PM	6 (1.6)	King’s College Hospital, Institute of Liver Studies, London, UK

SCR: standard competition ranking; USA: United States of America; UK: United Kingdom; NAC: N-acetylcysteine.

^aEqual authors have the same ranking number, and then a gap is left in the ranking numbers.

^bPercentage of publications for each author by the total number of documents.

Table 5.

Top 10 ranking of highly productive institutions that most frequently published articles related to NAC use in paracetamol overdose worldwide.

SCR^a	Institutions	Number of documents (%)
1st	Rocky Mountain Poison and Drug Center, USA	12 (3.27)
2nd	Royal Infirmary of Edinburgh, UK	10 (2.72)
3rd	University of California, San Francisco, USA	7 (1.91)
4th	Queen’s University, Kingston, Canada	6 (1.63)
4th	University at Buffalo State University of New York, USA	6 (1.63)
6th	Baylor College of Medicine, USA	5 (1.36)
6th	Newcastle Mater Misericordiae Hospital, Australia	5 (1.36)
6th	Universiti Sains Malaysia, Malaysia	5 (1.36)
6th	Vanderbilt University, USA	5 (1.36)
6th	Rigshospitalet, Denmark	5 (1.36)
6th	University of Newcastle, Australia	5 (1.36)
6th	Western University, Canada	5 (1.36)
6th	University of Maryland, Baltimore, USA	5 (1.36)
6th	University of Toronto, Canada	5 (1.36)
6th	University of Colorado School of Medicine, USA	5 (1.36)

SCR: standard competition ranking; USA: United States of America; UK: United Kingdom; NAC: N-acetylcysteine.

^aEqual institutions have the same ranking number, and then a gap is left in the ranking numbers.

Discussion

Goal and methodology assessment

The design of the present analysis permitted a worldwide assessment of the growth of scientific publications related to NAC use for paracetamol overdose. To the best of the authors’ knowledge, this is the first study to analyse the quantity and quality of NAC-based research worldwide. Our work focused primarily on assessing impact in the field (i.e. through the number of publications), the productivity of particular institutions or academic departments, the relative contribution of the top 10 most productive countries and the utility of the most preferred journals to NAC use for paracetamol overdose, which is considered as a sub-area of the multidisciplinary field of toxicology. This study was limited to 367 documents extracted from Scopus, bearing article titles with terms related to NAC use for paracetamol overdose and, therefore, cannot be generalized to the literature regarding NAC use for paracetamol overdose covered by other databases such as Google Scholar. On the other hand, there are various reasons for using Scopus database exclusively in this study. Firstly, it has been shown that Scopus can be used as the sole data source for bibliometric-based research in certain fields,^28,38 including toxicology.^12,14 Secondly, Scopus has a relatively large database of source journals and includes more expanded spectrum of journals than PubMed and Web of Science.¹⁶

Annual research productivity

The total publications found in Scopus between 1976 and 2012 indicated that research output was low in the first two decades but showed an obvious increase in the last decade, with peak publications in 2008–2011. Scientific publications related to NAC have followed the general evolution in scientific research productivity related to paracetamol overdose observed in the last decade and especially in the last years.¹⁴ Another explanation for this increase is the establishment of new research groups in the field of paracetamol overdose such as the Heard group from USA,^39

–43 the Zyoud group from Malaysia^44

–47 and the Waring group from UK.^48,49 After 2008, a new toxicological concept related to IV-NAC administration indicated that fewer anaphylactoid reactions are induced by NAC administration in patients with high serum paracetamol concentrations, suggesting that paracetamol might provide protective effects against NAC-induced anaphylactoid reactions.^44,48,49 This new concept opened the way for new confirmative researches for this new concept from the World.^44,49

However, the mechanism by which this occurs remains poorly understood. More research and efforts are needed to determine the exact mechanism(s) responsible for this reaction. An increased interest in NAC-related research may be provoked by the changing climate in healthcare and the need to improve clinical outcomes counterbalanced by high levels of cost-effectiveness. There has been an increased interest regarding the dose of NAC and the optimum duration for its use. For example, in UK the licensed indications for NAC have been amended recently, for example, clinical risk factor become less important.⁵⁰ More accurate risk stratification might minimize the need for using the antidote in patients at comparatively low risk of paracetamol toxicity and there has been a recent interest in detecting the biomarkers that could select a smaller cohort of patients who are at higher risk of liver disease.⁵¹ A recent study conducted by Rumack and Bateman⁵² suggested that the optimum management of patients with paracetamol overdose remains unclear, and there is insufficient data to evaluate the correct approach and whether the dose and duration of NAC administration should be modified in such patients. Rumack and Bateman discussed the issues that are needed to be elucidated for better changes in the dose and duration of NAC administration. Furthermore, the authors suggested that the potential for measuring other markers such as adducts, microRNA and cyclophilin A to improve treatment and patients’ outcomes is the subject of further research.⁵²

Source title

Another aspect of interest for this study in relation to the scientific publications related to NAC use for paracetamol overdose is the quality of research articles. It should be noted that 3 of the top 10 journals in which articles related to NAC use for paracetamol overdose were published carry IFs greater than 10 and have significant impacts in the field of medicine: New England Journal of Medicine, The Lancet and British Medical Journal. In our study, the average citation rate for NAC publications was 23.9 citations per document. This finding was more than the average number of citations per document published in toxicological journals,^7,9,12,14,53 which means that the field of NAC is still a hot issue in scientific research, and publications may have a larger audience than that of other toxicological aspects.

Research productivity and collaboration stratified by country

As expected, USA was the most productive country with its researchers being co-authors of 39.78% of all articles. These articles also amassed the highest h-index (h-index = 32). Furthermore, USA also had the largest number of collaborations with foreign countries during the period of study. This finding is consistent with a previous study which demonstrated that USA was the most productive country with its researchers being co-authors of 30.39% of all documents related to paracetamol overdose.¹⁴ The current research indicates that Australia has produced the greatest number of research articles from the Asia-Pacific region, whilst UK and Denmark have produced the most research articles from Europe, whereas Turkey, Iran and Israel have been the major research contributors from the Middle East. The 10 most productive countries that published articles on NAC include many nations that will be not familiar to the readers of other scientific productivity rankings.⁵⁴ In our study, the ranking of countries after adjusting for economy and population parameters differed conspicuously from those based on absolute production. After adjusting for economy and population power, USA, Iran and UK had the highest research productivity. We are unable to discuss this point in light of other results as we have not found any comparative studies. However, studies using the same tool for analysis have reported similar findings.^14,55,56 Countries with rapidly growing economies and with more funding and investment for research show a tendency towards an increasing number of publications. Based on our findings, besides GDP, population size is one of the main factors related to research productivity, as in USA. It would be interesting to explore how the growth of scientific publications related to NAC in the top 10 ranking of the most productive countries differed in quality, rather than in quantity, as shown by the h-index and average or median number of citations. Toxicology in Turkey and Iran has experienced a rapid development and showed great progress in education and research in conjunction with the economic development in these countries over the past two decades.^7,14 Based on the SJR, which is a portal that includes the scientific indicators developed from the information contained in the Scopus ^® database (Elsevier B.V.) for each journal and country, Turkey has the first rank in scientific productivity in the field of ‘Toxicology’ among Middle Eastern countries by publishing 1488 articles from 1996 to 2012, whilst Iran has published 873 articles in the same period and is ranked second in the Middle East.¹⁴ These results are similar to the findings of our study. Scientific collaboration combines researchers with the same interests together. It may increase productivity, make up for individual researcher’s deficiencies, provide easier access to public financing and result in greater prestige and visibility from collaboration with renowned research groups.^57
–59

Limitations

This study is not without limitations, most of which are the same as those of studies performed in other biomedical fields.^12,30,60,61 First of all, we used Scopus criteria for including NAC-related keywords in our study. Articles published in non-Scopus-cited journals were not included even though they may contribute to scientific productivity. Another limitation is that some articles did not contain NAC or related terms in the article titles even though these terms were mentioned in the text. Therefore, it is possible that the number of publications analysed in this study does not exactly represent all NAC-based research activity. Furthermore, some conference abstracts may be published by certain journals, and may then subsequently be published in the same or different journals in a year other than the one in which the original journal article was published. Finally, it should be noted that the research output for certain institutions could have been underestimated due to differences in the spelling of their English names across various articles. Therefore, such institutions might have two or more institution profiles in Scopus because their names were written differently in various articles.

Conclusion

These data reveal promising progress for research activity in the use of NAC for paracetamol overdose. The amount of NAC-based research activity was low in some countries. More effort is needed to bridge the gap in NAC-based research and to promote better evaluation of NAC use worldwide. Furthermore, our findings demonstrate that NAC use for paracetamol overdose remains a hot issue in scientific research and publications may have a larger audience compared with other toxicological aspects. Editors and authors in the field of toxicology might usefully promote the submission of work on NAC in future to improve their journal’s impact. Our study does not suggest changes to current practice or present guidelines. Our study encourages future research in detecting the biomarkers such as adducts, microRNA and cyclophilin A to improve treatment and patients’ outcomes.

Footnotes

Acknowledgement

The authors would like to thank An-Najah National University for giving the opportunities to access most recent information sources such as Scopus database.

Conflict of interest

The authors declared no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

References

Klein-Schwartz

Doyon

. Intravenous acetylcysteine for the treatment of acetaminophen overdose. Expert Opin Pharmacother 2011; 12: 119–130.

Mitchell

Thorgeirsson

Potter

Acetaminophen-induced hepatic injury: protective role of glutathione in man and rationale for therapy. Clin Pharmacol Therapeut 1974; 16: 676–684.

Prescott

Newton

Swainson

Successful treatment of severe paracetamol overdosage with cysteamine. Lancet 1974; 1: 588–592.

Sandilands

Bateman

. Adverse reactions associated with acetylcysteine. Clin Toxicol (Philadelphia) 2009; 47: 81–88.

Miro

Montori

Ramos

Trends in research activity in toxicology and by toxicologists in seven European countries. Toxicol Lett 2009; 189: 1–4.

Biglu

Omidi

. Scientific profile of pharmacology, toxicology and pharmaceutics fields in Middle East Countries: impacts of Iranian scientists. Int J Adv Pharmaceut Sci 2010; 1: 122–127.

Delirrad

Rashidi

Karimi

. A bibliometric analysis of toxicology publications of Iran and Turkey in ISI web of science. Iran J Toxicol 2013; 6: 735–745.

Jones

. Impact of JAT publications 1981-2003: the most prolific authors and the most highly cited articles. J Anal Toxicol 2004; 28: 541–545.

Bird

. Journal impact factors, h indices, and citation analyses in toxicology. J Med Toxicol 2008; 4: 261–274.

10.

Zhang

. Bibliometrics analysis for research paper on occupational poisoning in China between 1999 and 2008. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi 2010; 28: 870–872.

11.

Zyoud

Al-Jabi

Sweileh

A bibliometric analysis of toxicology research productivity in Middle Eastern Arab countries during a 10-year period (2003-2012). Health Res Policy Syst 2014; 12: 4.

12.

Zyoud

Al-Jabi

Sweileh

A bibliometric analysis of research productivity of Malaysian publications in leading toxicology journals during a 10-year period (2003–2012). Hum Exp Toxicol. Epub ahead of print 6 February 2014. DOI: 10.1177/0960327113514101.

13.

Robert

Saenz-Feijoo

Gaudy

Quantitative analysis of the scientific literature on acetaminophen in medicine and biology: a 2003-2005 study. Fundam Clin Pharmacol 2009; 23: 159–168.

14.

Zyoud

Al-Jabi

Sweileh

. Worldwide research productivity of paracetamol (acetaminophen) poisoning: a bibliometric analysis (2003-2012). Hum Exp Toxicol. Epub ahead of print 22 April 2014. DOI: 10.1177/0960327114531993.

15.

Lin

Rosenblatt

. Shifting patterns of economic growth and rethinking development. J Econ Policy Reform 2012; 15: 171–194.

16.

Falagas

Pitsouni

Malietzis

Comparison of PubMed, Scopus, web of science, and Google scholar: strengths and weaknesses. FASEB J 2008; 22: 338–342.

17.

Garcia-Lopez

. Bibliometric analysis of Spanish scientific publications on tobacco use during the period 1970-1996. Eur J Epidemiol 1999; 15: 23–28.

18.

De Battisti

Salini

. Robust analysis of bibliometric data. Stat Methods Appl 2013; 22: 269–283.

19.

Wallin

. Bibliometric methods: pitfalls and possibilities. Basic Clin Pharmacol Toxicol 2005; 97: 261–275.

20.

Tan

H-Z

Y-S

. A bibliometric analysis of research on proteomics in Science Citation Index Expanded. Scientometrics 2014; 98: 1473–1490.

21.

Smith

. Impact factors, scientometrics and the history of citation-based research. Scientometrics 2012; 92: 419–427.

22.

Scopus. SciVerse Scopus fact sheet. SciVerse® Scopus, http://www.elsevier.com/online-tools/scopus (2013, accessed 14 September 2013).

23.

Burnham

. Scopus database: a review. Biomed Digit Libr 2006; 3: 1.

24.

Zyoud

Al-Jabi

Sweileh

. Bibliometric analysis of scientific publications on waterpipe (narghile, shisha, hookah) tobacco smoking during the period 2003-2012. Tob Induc Dis 2014; 12: 7.

25.

Zyoud

Al-Jabi

Sweileh

. A Scopus-based examination of tobacco use publications in Middle Eastern Arab countries during the period 2003-2012. Harm Reduct J 2014; 11: 14.

26.

Hirsch

. An index to quantify an individual's scientific research output. Proc Natl Acad Sci USA 2005; 102: 16569–16572.

27.

Meho

Rogers

. Citation counting, citation ranking, and h-index of human-computer interaction researchers: a comparison of Scopus and Web of Science. J Am Soc Inf Sci Technol 2008; 59: 1711–1726.

28.

Smith

. Identifying a set of ‘core’journals in occupational health, part 2: lists derived by bibliometric techniques. Arch Environ Occup Health 2010; 65: 173–175.

29.

World Bank Group. Countries and Economies 2012, http://data.worldbank.org/country (2013, accessed 25 November 2013).

30.

Sweileh

Zyoud

Sawalha

Medical and biomedical research productivity from Palestine, 2002–2011. BMC Res Notes 2013; 6: 41.

31.

Gearing

Mian

Barber

A methodology for conducting retrospective chart review research in child and adolescent psychiatry. J Can Acad Child Adolesc Psychiatry 2006; 15: 126–134.

32.

Banks

. Designing medical record abstraction forms. Int J Qual Health Care 1998; 10: 163–167.

33.

Kimberlin

Winterstein

. Validity and reliability of measurement instruments used in research. Am J Health Syst Pharm 2008; 65: 2276–2284.

34.

Allison

Wall

Spettell

The art and science of chart review. Jt Comm J Qual Improv 2000; 26: 115–136.

35.

Yaffee

RA.

Common correlation and reliability analysis with SPSS for Windows, http://www.nyu.edu/its/statistics/Docs/correlate.html (2007, accessed 23 April 2011).

36.

Pallant

. SPSS survival manual: a step by step guide to data analysis using SPSS for windows version 15. 3rd ed. Berkshire: Open University Press, McGraw-Hill Education, 2007.

37.

Piperno

Berssenbruegge

. Reversal of experimental paracetamol toxicosis with N-acetylcysteine. Lancet 1976; 2: 738–739.

38.

Smith

. Highly cited articles in environmental and occupational health, 1919–1960. Arch Environ Occup Health 2009; 64(Suppl 1): 32–42.

39.

Bebarta

Kao

Froberg

A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose. Clin Toxicol 2010; 48: 424–430.

40.

Heard

Green

. Acetylcysteine therapy for acetaminophen poisoning. Curr Pharmaceut Biotechnol 2012; 13: 1917–1923.

41.

Heard

Schaeffer

. Massive acetylcysteine overdose associated with cerebral edema and seizures. Clin Toxicol 2011; 49: 423–425.

42.

Varney

Buchanan

Kokko

Acetylcysteine for acetaminophen overdose in patients who weigh >100 kg. Am J Ther 2014; 21: 159–163.

43.

Wang

Monte

Bagdure

Hepatic failure despite early acetylcysteine following large acetaminophen-diphenhydramine overdose. Pediatrics 2011; 127: e1077–e1080.

44.

Zyoud

Awang

Sulaiman

SAS

Relationship between serum acetaminophen concentration and N-acetylcysteine-induced adverse drug reactions. Basic Clin Pharmacol Toxicol 2010; 107: 718–723.

45.

Zyoud

Awang

Sulaiman

SAS

Effects of delay in infusion of N-acetylcysteine on appearance of adverse drug reactions after acetaminophen overdose: a retrospective study. Pharmacoepidemiol Drug Saf 2010; 19: 1064–1070.

46.

Zyoud

Awang

Sulaiman

SAS

N-acetylcysteine-induced headache in hospitalized patients with acute acetaminophen overdose. Fund Clin Pharmacol 2011; 25: 405–410.

47.

Zyoud

Awang

Sulaiman

SAS

Incidence of adverse drug reactions induced by N-acetylcysteine in patients with acetaminophen overdose. Hum Exp Toxicol 2010; 29: 153–160.

48.

Pakravan

Waring

Sharma

Risk factors and mechanisms of anaphylactoid reactions to acetylcysteine in acetaminophen overdose. Clin Toxicol 2008; 46: 697–702.

49.

Waring

Stephen

Robinson

Lower incidence of anaphylactoid reactions to N-acetylcysteine in patients with high acetaminophen concentrations after overdose. Clin Toxicol 2008; 46: 496–500.

50.

Thompson

Fatima

Shah

Impact of amending the acetylcysteine marketing authorisation on treatment of paracetamol overdose. ISRN Toxicol 2013; 2013: 5.

51.

Dear

Antoine

. Stratification of paracetamol overdose patients using new toxicity biomarkers: current candidates and future challenges. Expert Rev Clin Pharmacol 2014; 7: 181–189.

52.

Rumack

Bateman

. Acetaminophen and acetylcysteine dose and duration: past, present and future. Clin Toxicol (Philadelphia, Pa) 2012; 50: 91–98.

53.

Jang

Rusyniak

. Hard impact: journal impact factor and JMT. J Med Toxicol 2011; 7: 256–258.

54.

Essential Science Indicators. Top 20 Countries in ALL FIELDS, 2001-August 31, 2011, http://archive.sciencewatch.com/dr/cou/2011/11decALL/ (2012, accessed 20 September 2013).

55.

Cheng

Zhang

. Worldwide research productivity in the field of rheumatology from 1996 to 2010: a bibliometric analysis. Rheumatol (Oxford) 2013; 52: 1630–1634.

56.

Soteriades

Falagas

. A bibliometric analysis in the fields of preventive medicine, occupational and environmental medicine, epidemiology, and public health. BMC Public Health 2006; 6: 301.

57.

Abramo

D’Angelo

Di Costa

. Research collaboration and productivity: is there correlation? High Educ 2009; 57: 155–171.

58.

de Granda-Orive

Villanueva-Serrano

Aleixandre-Benavent

Network of international scientific collaboration on smoking: analysis of coauthorship through the Science Citation Index (1999-2003). Gac Sanit 2009; 23: 222. e234–e243.

59.

Lee

Bozeman

. The impact of research collaboration on scientific productivity. Social Stud Sci 2005; 35: 673–702.

60.

Tao

Zhou

Scientific publications from mainland China, Taiwan, and Hong Kong in integrative and complementary medicine journals: a ten-year literature survey. Am J Chin Med 2011; 39: 639–649.

61.

Zyoud

Al-Jabi

Sweileh

Assessing the scientific research productivity of a leading toxicology journal: a case study of Human & Experimental Toxicology from 2003 to 2012. SAGE Open Med 2014; 2: 2050312114523424.

Global research productivity of N -acetylcysteine use in paracetamol overdose

Abstract

Purpose:

Methods:

Results:

Conclusion:

Keywords

Introduction

Methods

Search strategy

Indices of research productivity

Ethical approval

Statistical analysis

Results

Type of documents

Annual research productivity

Research productivity and collaboration stratified by country

Source title

Research productivity stratified by authors and institutions

Discussion

Goal and methodology assessment

Annual research productivity

Source title

Research productivity and collaboration stratified by country

Limitations

Conclusion

Footnotes

Acknowledgement

Conflict of interest

Funding

References