Current Trend of Hydroxychloroquine Research Publications: A Scientometric Analysis

Hydroxychloroquine (HCQ) is one of the extensively used preventive drug in the world. In order to filter out the research strength and weaknesses of research areas of HCQ publications of selective countries, the present study analyses the thematic or subject specialization index, relative priority index, and relative specialization index of hydroxychloroquine research publications from 1989 to 10th June 2020. The top thirty-five productive research areas and fifteen leading countries have been taken for this analysis. The analysis identifies the 209 significant active sub-specialized research areas of the HCQ research of the highest productive countries. India was found to be the most specialized country in Hydroxychloroquine research. Public Environmental Occupational Health is the most specialized research area of HCQ publication. The most significant number of HCQ research publications output is coming under the research areas Rheumatology. The most significant number of research growth was observed in the year 2019. The implications of the study are discussed.


INTRODUCTION
Hydroxychloroquine (HCQ) is one of the most secure and beneficial medicine included in the WHO's essential list of medicines. Plaquenil is the brand name of Hydroxychloroquine medicines. It is one of the most popular preventive medicines to prevent and treat malaria, and it is also known as an antimalarial drug. It is also utilized for the healing of rheumatoid arthritis, porphyria cutanea tarda, and lupus. The chemical formula of Hydroxychloroquine is C 18 H 26 ClN 3 O. In this epidemic period of COVID 19, the study of this type of preventive medicine acquired great importance. Nowadays, numerous researches on HCQ are conducting in connection with COVID 19 treatment. In their investigations regarding hydroxychloroquine, Li, X. et al. [1] found it helpful for COVID-19 patients. Their study recommends HCQ as preventive medicine for healthy persons who are not showing COVID 19 symptoms. This study also points out that this medicine has minor side effects. But while prescribing HCQ for COVID 19 patients, it is essential to evaluate their immune profile thoroughly. Sarah, M. L. et al., [2] in their research about the Safeness of HCQ use in COVID-19 patients, reported no severe side effects and no death experience associated with hydroxychloroquine. Skipper, C. P. et al. (2020), [3] in their examination on the application of HCQ on early and mild corona symptoms showing patients, reveals no significant reduction of disease intensity in such patients. Mehra, M. R. et al. (2020), [4] in their survey about HCQ for the treatment of COVID-19 patients, discloses that no measurable benefit found HCQ with or without the combination of macrolide some harmfulness of the use of this medicine. Derwand, R., and Scholz, M. (2020) [5] suggested that zinc supplements will strengthen the efficiency of hydroxychloroquine medicine in aged COVID 19 patients. And it is also beneficial for coronavirus patients having heart disease, lung disease, or diabetes. Geleris, J. et al. (2020), [6] in their study on Hydroxychloroquine in Covid-19 inpatients, exposed no benefit or danger in using this medicine; their findings did not support its use in such patients. They also recommend more clinical trials in this regard. Gautret, P. et al. (2020) [7] conducted a clinical study in eighty COVID-19 patients about the benefit of the combinational use of hydroxychloroquine with azithromycin. Their observational studies identified that out of two aged patients, and others recovered immediately with the help of this medicine. The review of literature manifests that scientists throughout the globe are performing numerous researches on hydroxychloroquine. But still, there is no scientometric study undertaken. This scientometrics analysis will help locate the most productive journals, authors, institutions, most specialized countries and their research areas, most productive countries, most productive Journal of Scientometric Research, Vol 10, Issue 2, May-Aug 2021 exported to excel sheets. The country-wise research output of other subject areas (other than the top thirty-five research areas) was also collected and tabulated in the excel file. Concerned statistical techniques and tools were employed to measure exported data according to the objectives of the analysis.

Limitation of the Study
Two limitations perceived during the analysis are as follows: 1. Variations in the number of records found while taken the refined and downloaded fifteen country-wise lists of research areas. However, thirty-five research area-wise country share taken as final.
2. One hundred forty-two data were missed in the database while cross-analyzed the total number of research areas wise and country-wise research output lists.

METHODOLOGY
Mainly five methods and techniques of scientometrics are used to analyze HCQ publications. These include Exponential Growth Model, Relative Priority Index, Thematic or subject specialization index, Relative Specialization Index and Publication Efficiency Index.
In order to measure the exponential growth pattern of HCQ research publications, observed data of research output has been applied in the equation of the expected number of publications. Y = K + ab x Here, 'Y' is the expected number of publications.
K is the asymptote, and a and b are constants. K can be calculated from the formula, Where, S1, S2 and S3 are the three subtotals to find out the value of K. 1/ X = Unit of time n = Number of years research areas, yearly publication output, growth pattern etc., that are relevant to their research. This analysis mainly concentrates on sieving out the active and inactive research areas of HCQ Research publications of the top fifteen productive nations. So that, scientific community of this domain can focus more on static research areas of their corresponding countries to make them more active.

Objectives
This study mainly analyses the research publication trend of hydroxychloroquine during the period 1989 to 10 th June 2020.
The following research questions are addressed by this study 1. To identify the top prolific journals, authors, and organizations in the field of HCQ research publications 2. To analyze the annual output and exponential growth model of HCQ publications 3. To find out thirty-five of the most prolific research sub-specialized areas of HCQ publications and its output in the fifteen most leading countries.

4.
To measure the relative priority index, thematic or subject specialization index, and relative specialization index of the top fifteen countries in this discipline's thirty-five sub-specialized research areas for the identification of active and inactive research areas of HCQ research publications of corresponding countries.

5.
To analyze yearly citations received and publication efficiency index of HCQ research articles.

Data Collection
Data requisite for this study was extracted from the web of Science Core database for the timespan 1989 to present, which includes three main citation indexes, such as Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index, Arts and Humanities Citation Index (A&HCI). The Keywords "Hydroxychloroquine," "HCQ," and "Plaquenil" were used by selecting the topic search field in the basic search box of the web of science core database for extracting data. Timespan has been chosen for the year 1989 to 2020. Data were downloaded from the database on 10 th June 2020. A total of 4886 data were found to be available in this database during the prescribed time frame. All essential data such as total publication output, year-wise, author wise, journal wise, institution wise, country wise, research area-wise lists required for this study were refined and imported to CSV excel files.
Analyzing data more accurately for measuring SSI, RPI and RSI, the top thirty-five research areas of HCQ publications refined one by one. Each thirty-five research areas country-wise list refined and imported to excel files. The top productive fifteen countries have been taken for cross analyzing the data, and each country's research area wise list has been refined and The relative Priority Index is a statistical tool for applying cross-national comparisons. This index is similar to the Activity Index proposed by Fame (1977) [8] subsequently used among others by Nagpaul (1995) [9] Schubert and Braun (1986), [10] Carpenter et al. (1988) [11] and Sangam, S. L. (2018) [12] Relative Priority Index ( ) Where, 2. The priorities of different countries to a given subfield in a given time.
3. The priorities of the given subfield in different periods.
The Thematic or subject specialization index of a country (a region or an institution) the ratio of its world share is one particular discipline to its world share for all disciplines. (Glänzel, W. (2000), [13] Romo-Fernández., et al. (2011), [14] Arencibia-Jorge, R. (2016), [15] Zacca-González, G. (2018). [16] TSI/SSI can be measured in two methods. Two methods generate the same result. In the first method, Thematic or subject specialization index in discipline Where discipline 'i' is particular disciplines taken for the study In the second method, the Thematic or subject specialization index is measured by the equation, Where, X a = number of articles published by group X in discipline α X t = Total Number of articles published by reference group X Y a = number of articles published by group Y in discipline α X t = Total Number of articles published by reference group Y This equation of TSI/SSI is similar to RPI without the multiplication of 100." In both methods, if the value of TSI/ SSI is higher than 1, it indicates that the country specializes in that particular discipline. TSI/ SSI is less than one denotes that that country is not specialized in that discipline. If it is equal to one, that country shows a neutral situation means no relative specialization in that particular discipline. Here, the first method took for analyzing the thematic or subject specialization index of HCQ publications. Glänzel (2003) [17] has been introduced the Relative Specialization index (RSI).
According to him, the values of RSI lie between −1 and +1.
If the rate of RSI is equal to −1, it denotes that research in that field is lower than average activity. If RSI is equal to zero, it indicates moderate or average research activity. If RSI is equal to 1, it displays all the research activity is more remarkable than the average priority index and occurred in that area only.
No research activity occurred in other fields. It is balanced the positive values of RSI with the negative ones.
Citation measures the number of times articles cited by other researchers for writing their research paper. Analysis of PEI implemented for estimating relative research effort, and this analysis is based upon the citations received to the research articles by the authors. The formula of Guan, J. and Ma, M.

Prolific Journals, Authors, Organizations of HCQ Publications
Journal of Rheumatology has 216 (4.42%) articles in HCQ research publications, and it is found to be a high-yielding journal. Lupus is the second leading journal with 211      Here, n = 11 years (number of subtotal years) ) . In 1993, 1995 to 1999, 2001, 2002, 2007, 2013 to 2019 observed value is higher than the expected value of publication output. From 2013 onwards, publications outgrowth is higher than the expected output. But in 2014, data was found to be lower than in 2013. Out of 32 remaining years, the other sixteen years publication output is lower than the expected values. Chi-square test of goodness of fit implemented to identify the exponential growth model of HCQ research publications. The calculated Chi-square value X 2 from Table 1 is 308.15. It is found to be considerably higher than the critical Chi-square value of 43.773 at a 0.05 (5%) level of significance for 30 degrees of freedom. So, it can be concluded that 95% of HCQ research publications do not fit with the exponential growth model. There is only a 5% of chance of rejection. The yearly output versus the expected annual output of HCQ publications is illustrated in Figure 4.  Figure 4, it is visible that the yearly outgrowth of HCQ research publications does not follow the exponential growth pattern. Observed yearly outgrowth is lower than expected outgrowth, especially at the beginning and middle stages of growth.
Thirty-five most prolific research sub-specialized group of HCQ publications and its publication output in fifteen most leading countries The top active 35 research area sub-specialities of HCQ and its research share from the most productive 15 countries from 1989 to 10 th June 2020 are listed in Table 2. Row of Table 2 denotes the most active research sub-specialities, and columns constitute the most active research sub-spec most leading countries. The largest number of research publications on HCQ is coming under the research area Rheumatology with 1764 articles. The second place of research rank was Dermatology with 448 articles, followed by General Internal with 438 research publications. Other research areas in their decreasing order of research output are listed in Table 2.

Thematic or subject specialization index (TSI/SSI)
The primary method mentioned in the methodology part of this article has been used to analyze TSI/ SSI. For this, first, it is required to analyze the country-wise share of each sub-specialized research area. Relevant data in Table 2 is employed for analyzing each country-wise share of all thirtyfive sub-specialized research areas of HCQ publications. Similarly, for analyzing the thematic or subject specialization index of other sub-specialized research areas, first identified the world share of each research area and those values displayed in Table 4. The row of Table 4 constitutes the thirty-five prolific sub-specialized research area of HCQ publications, and columns depict the most productive fifteen nations.  Table 4 in the Thematic or subject specialization index equation. And thus obtained the value of TSI/SSI of all thirty-five-research sub-specialized    Table 3 and Table 4 are found to be similar without the multiplication of 100 in Table 3. So, it is evident that the second method to find out SSI, which is mentioned in the methodology part, gives the same result as that of the first approach. From the average value of Specialization Indices of  Figure 5. Also, SSI and RPI of the top thirty-five research areas of HCQ publications is illustrated in Figure 6.

It is substituting all specific values of
Journal of Scientometric Research, Vol 10, Issue 2, May-Aug 2021

Relative Specialization Index (RSI)
Values of RPI from Table 3 has been taken for measuring the relative specialization index of HCQ publications. In the same manner, all other RSI values are measured in Table 6. Out of 540 measured RSI values, 120 values shows -1, and it is highlighted with shaded cells in Table 6. Research activity in these one hundred and twenty sub-specialized subject areas of HCQ research publications is lower than the average research activity. From Table 2, it can visible that the research output of these sub-specialized subject areas is zero. So, all countries belonging to these 120 sub-specialized areas need to prioritize their research activity in these fields. No average value (i.e., RSI ≠ 0) is observed from the 540 calculated RSI. All the other 420 sub-specialized subjects are greater than the average value(RSI>0). Hence, it can assume that

Citation Analysis and Publication Efficiency Index
The influence of HCQ research articles in the scientific community is measured by analyzing citations received for its articles.  Table 7 demonstrated year-wise citations, the average citations received per paper and the PEI of HCQ.
From Table 7 it can identify that while the rate of ACPP increased, the rate of PEI also increased. So, they are directly proportional to each other.

Citation Analysis and Publication Efficiency Index
The influence of HCQ research articles in the scientific community is measured by analyzing citations received for its articles. HCQ publications attained the highest citation of 6018(6%) in the year 2011. And it is for 167 research publications. The second highest citations, 5382 (5.37%) received in 2014 for 243 articles. While analyzing citations, it is essential to consider the number of publications too. Analysis of PEI implemented for the cross-comparisons of citations with the number of publications of HCQ. Table 7 demonstrated year-wise citations, the average citations received per paper and the PEI of HCQ.
From Table 7 it can identify that while the rate of ACPP increased, the rate of PEI also increased. So, they are directly proportional to each other. The value of PEI (4.45) and ACPP (91.30) was topmost in 1989 since ten articles of the corresponding year achieved 913 citations. So, the research output of HCQ has dramatically influenced the research community in that year. Seventy-four articles published in 2003 gained 4423 (4.41%) citations, which is the second fruitful year of this field. Third, highly influential articles were published in 2005-Ninety-nine articles of this year 4403 (4.39%) citations. Out of thirty-two measured rates, twenty-five values of PEI are greater than one, so the research impact of HCQ articles is found to be high in those years. In 2013 and from 2015 onwards rate of PEI is decreasing. Articles published in recent years may attain more citations in the coming years. Anyway, the average value of PEI indicates that the overall research effort and impact is HCQ articles is excellent.

CONCLUSION
Analysis indicates that HCQ publication shows neither uniform increase nor decrease during the selected period of study. Some fluctuations throughout the study can observe.
The Chi-square test proves that HCQ research output does not follow an exponential growth pattern. The remarkable efficiency and quality of HCQ research articles and their impact were confirmed with the PEI examination. RPI and TSI/SSI rates determine the priorities and specialization of each fifteen countries in each thirty-five sub-specialized research areas in the selected time era. Analysis indicates that the highest number of HCQ research publications is from the research area of Rheumatology, and the highest number of articles share is from the USA. Still, the average TSI/ SSI and RPI show that Public Environmental Occupational Health is the most sub-specialized research area, and India is the top specialized country of HCQ publications. China, Japan, Canada, Australia and the USA are the other specialized countries of HCQ research. 'Orthopaedics' of the Netherland is the most active sub-specialized research field of HCQ publications. RSI values indicate 120 static sub-specialized research fields of fifteen countries, and it also demonstrates the overall research performance of countries in HCQ research. RSI prove that research running of the USA is sufficient in all thirty-five sub-specialized fields of HCQ research. Analysis of PEI certifies, the overall publication efficiency and research impact of HCQ articles are honourable. This analysis help researchers to detect the active and inactive research fields of HCQ publication of different countries from 1989. Hence researchers can focus on the inactive areas to make them more active. It also helps the different countries recognize their strength and weaknesses in their research in the selected areas of analysis. This study mainly supports the scientific community for identifying the leading journals, authors, research institutions, and countries of HCQ research publications.