INTRODUCTION:

The World Health Organization (WHO) in 1997 defined drug utilization as the marketing, distribution, prescription, and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequence [1]. Drug utilization studies previously have been conducted mostly for marketing purposes and data was not available for academic purposes to health care professionals.

The virtual explosion in the marketing of new drugs, the wide variations in the patterns and extent of drug prescribing, the growing concern about Adverse drug reactions and cost of drugs has led the health professionals to conduct drug utilization studies [1]. They create a sound socio-medical health economic basis for health care decision making, the purpose of a Drug Utilization Evaluation studies is to describe, verify and finally improve the quality of drug usage. Intensive Care Unit (ICU) patients are a heterogeneous group, who often suffer from severe illness, multiple organ dysfunction, and coexisting medical disorders. These patients have high mortality and morbidity and require a high level of intensive care [2].

World Health Organization specifies drug use indicators for adoption in drug utilization studies [3]. Drug utilization studies play a vital role in the estimation of quality healthcare systems [4]. General medications utilization also called as drug utilization mainly focuses on the parameters related to the prescribing, dispensing, and administering of medications, its therapeutic efficacy or adverse effects etc [5,6,7].

The resistance of the hospital-acquired bacteria to the antibiotics is the worldwide problem, which leads to morbidity and mortality and length of hospitalization and increased healthcare expenditure [8]. In a study of Drug utilization pattern from an ICU in south India, 200 patients received 1469 drugs and 250 antibiotics during the length of stay in the hospital, the average number of drugs and antibiotics prescribed per patient were 7.3 and 1.25, antibiotics constituted 17.01% of the total drug prescribed [9]. The ultimate goal of Daily Defined Dose (DDD) is the improving of drug use to analyze drug utilization pattern for implementing rational antibiotic policies having positive economic Benefit and therapeutic management can be improved [10]. By implementing local antibiotic compliance programs and medical consultation for infectious diseases, restrictions can be generated by utilizing a wide range of different antibiotics for the treatment of certain disease [11].

Cost-minimization analysis (CMA) measures and compares input costs, and assumes outcomes to be equivalent [12]. CMA involves in the comparison of equivalents of same generic drugs having the same dose and pharmaceutical properties (brand versus generic, generic made by one company compared with another company), only the cost of the medicine can be compared to the same outcomes can be generated. We compare the cost of most frequently prescribed drugs and other brands with low cost that is available in the hospital. Most frequently prescribed antibiotics and other than antibiotics among the prescribed medications were mandatory for cost minimization analysis.

Cost-minimization analysis is a procedure involved in calculating drug costs to a proposed drug having the less cost or therapeutic modality. Cost minimization analysis is the method of cost evaluation to a certain dose of a drug which has to be administered [13]. Therefore, this method is useful for distinguishing the generic entities of the same drug having different costs. Clinical pharmacists play a vital role in prescribing clinically cost-effective appropriate drugs to the physicians for pharmaceutical cost management Thus, the economic burden and quality in patient care can be promoted. Clinical Pharmacists are in the position to make suggestions and interventions that can save cost by reducing economic burden and enhance the quality of patient care. They can also encourage prescribers to make cost-effective choices of drugs when clinically appropriate. The aim of this prospective descriptive study was to analyze general medications utilization, cost minimization analysis of antibiotics in hepatic impairment patients at tertiary care hospital and to analyze rationality among the prescriptions.

METHODOLOGY:

A Hospital based prospective observational study were conducted in the Department of General Medicine in Manipal Super Specialty Hospital, Vijayawada, India. During the period of the study July – December 2017 (six months), Around two hundred (200) patients data were collected and studied, who were admitted into the Department of Medicine as hepatic impairment cases, within the study duration. The data was collected regularly from the General Ward of Medicine, without interfering with their treatment. We excluded the patients who are unable to participate in this study and outpatients & pregnant women were also excluded. Each patient age, sex, diagnosis (only hepatic impairment) and prescribed generic and brand names of the drugs were recorded. The collected data was analyzed to study- route of administration of drugs, antibiotics prescribed for liver impairment patients and the outcome of the treatment like levels of liver function tests were evaluated. Cost minimization analysis was done by calculating the cost difference between similar generic drugs with different brand names available in the hospital. Drugs that had cost difference greater than 30 percent has minimize the cost.

High cost brand – low cost brand

Percentage cost difference = ––––––––––––––––× 100

Low cost brand

Data Analysis:

Data was analyzed in MS Excel and descriptive statistics were used for analyzing the result of the study.

RESULTS:

Total numbers of 200 hepatic impairment patients were distributed according to the age group along with gender distribution. Out of 200 cases, female patients were 69(34.5%) and male patients were 131 (65.5%). The majority of the patients out of 200 were in the age group 31-40 (n=46, 23%) [Table 1]. The results are evident that maximum cases of Hepatic Impairment were found to be pancreatitis 61(30.5%), followed by CLD ˃ Cholelithiasis ˃ Hepatitis ˃ ALD ˃ Jaundice ˃ Metabolic Encephalopathy ˃ Bile Duct Injury ˃ Cirrhosis [table 2]. In this study, it was observed that all the cases found in hepatic impairment are associated due to the precipitating factors such as alcohol and smoking [table 3]. A total number of 75 patients were found to be precipitated hepatic impairment. In which 48 patients (31%) are alcoholic, 4 patients (2%) are smokers were as 23 patients (11.5%) were both alcoholic and smokers. Out of 1469 medications, the highly prescribed formulation was found to be parenteral dosage forms 742 (50.51%), followed by solid dosage forms (Tablets and Capsules) 547 (37.2%), Syrups 82 (5.5%), Nebulizations 65 (4.42%), and others 33 (2.24%) were well-prescribed formulations, prescribing in generic names was a good thing and easily understandable 412 (28.01%) generic names were practiced by physicians when compared with brand names 1057 (71.9%) [table 4]. In Hepatic Impairment patients, the most commonly used drugs are antibiotics (17%), followed by Vitamin Supplements ˃ Proton Pump Inhibitors ˃ Hepato Protective Agents ˃ Anti-emetics > Analgesics and NSAIDs ˃ Anti Hypertensive's ˃ Anti asthamatic followed by other drugs [table 5]. In Hepatic impairment patients the most commonly prescribed drugs other than antibiotics are Pantoprazole (82%) followed by Ondansetron(32.5%), Paracetamol(32%), Tramadol (22.5%), Silymarin (17%), Mecon plus (11.5%), Ultracet (10.5%), Optineuron (10.5%), Duolin (10%), Rabeprazole (9.5%), Reheptin (8.5%), Ranitidine (8%) [table 6].

The cost minimization data analysis shows that most of the drugs that are frequently prescribed other brands available in the hospital. In this study observed that drugs like Meropenem, Ceftriaxone, Ranitidine, Ciprofloxacin, Amoxicillin, Rabeprazole, Paracetamol, and combination drugs like Imipenem + Cilastatin, Cefoperazone + Sulbactam, Tramadol + Paracetamol, Metadoxine + Silymarin + Vit B6 + Folic Acid + L-O + L-A drugs were greater than 30 percent cost difference. Octreotide, Ertapenem drugs were less than 30 percent cost difference when compared with two brands of the generic drug but the cost of each brand greater than 500 INR so have to minimize the cost [table 7]. Meropenem, Cefoperazone + Sulbactam, Imipenem + Cilastatin, drugs were greater than 30 percent cost difference and also greater than 500 INR but in case of Metadoxine + Silymarin, Ciprofloxacin, Cefoperazone + Sulbactum greater than 30 percent cost difference when compared with two brands of the generic drug but the cost of each brand less than 500 INR. The Calculation is done by using the mentioned formula in methodology.

Tab/Fig-1: Distribution of the Patients According to Age Groups

S. No	Age	Male	Female	Total	Percentage of Total Population
1.	10-20	8	11	19	9.5%
2.	21-30	17	11	28	14%
3.	31-40	31	15	46	23%
4.	41-50	28	7	35	17.5%
5.	51-60	28	8	36	18%
6.	61-70	15	13	28	14%
7.	71-80	4	4	8	4%

Tab/Fig-2: Percentage Prevalence among Hepatic Impairment Patients

S. No	Disease	Male	Female	Total	Percentage prevalence
1.	Pancreatitis	43	18	61	30.5%
2.	CLD	26	13	39	19.5%
3.	Hepatitis	14	4	18	9%
4.	Jaundice	10	4	14	7%
5.	Cholelithiasis	11	20	31	15.5%
6.	Metabolic Encephalopathy	9	3	12	6%
7.	Bile Duct Injury	2	3	5	2.5%
8.	ALD	16	-	16	8%
9.	Cirrhosis	-	4	4	2%

CLD- chronic liver disease, ALD- acute liver disease

Tab/Fig-3: Distribution of Patients according to their Habits that precipitate hepatic Impairment

S. No	Disease with Habitat	No. of. Patients	Percentage
1.	Pancreatitis + Alcoholic	22	29%
2.	Hepatitis + Alcoholic	3	4.0%
3.	CLD + Alcoholic	14	19%
4.	Pancreatitis + Alcoholic + Smoker	12	16%
5.	CLD + Alcoholic + Smoker	7	9.33%
6.	Cholilithiasis + Smoker	4	5%
7.	ALD + Alcoholic	9	12%
8.	ALD + Alcoholic + Smoker	4	5%

Tab/Fig-4: Prescription Catalog

S. No	Prescription Catalog	Results
1.	Total number of prescription analyzed	200
2.	Total number of medications prescribed	1469
3.	Average number of medications per prescription	7.3 (1-10)
4.	Percentage of medications prescribed by generic name	412/1469 (28.01 %)
5.	Percentage of medications prescribed by brand name	1057/1469 (71.9 %)
6.	Percentage of medications prescribed by solid dosage form	547/1469 (37.2 %)
7.	Percentage of medications prescribed by parenteral	742/1469 (50.51 %)
8.	Percentage of medications prescribed by nebulizations	65/1469 (4.42%)
9.	Percentage of medications prescribed by syrups	82/1469 (5.5%)
10.	Percentage of medications prescribed by other formulations	33/1469 (2.24%)

Tab/Fig-5: Drug usage pattern

S. No	Category	Number of drugs	Percentage
1	Antibiotics	250	17%
2	Vitamin supplements	193	13.1%
3	Proton pump inhibitor	189	12.8%
4	Hepatoprotective agents	95	6.4%
5	Antiemetics	67	4.56%
6	NSAIDS	64	4.35%
7	Analgesics	64	4.35%
8	Antihypertensives	51	3.47%
9	Antiasthmatic	48	3.26%
10	Opioid analgesics	45	3.05%
11	Laxatives	42	2.85%
12	Antidiabetics	42	2.85%
13	Combination drugs & others	42	2.85%
14	Antiulcer	41	2.79%
15	Antihyperlipidimics	35	2.38%
16	Gall stone dissolution agents	30	2.04%
17	Antihistaminics (H1 blockers)	22	1.49%
18	Anticoagulants	21	1.42%
19	Electrolyte supplement	19	1.29%
20	Antihistaminics (H2 blockers)	16	1.08%
21	Somatostatin analogues	15	1.02%
22	Corticosteroids	14	0.95%
23	Bronchodilators	13	0.88%
24	Mucolytics	13	0.88%
25	Antipsychotics	11	0.74%
26	Antiviral	8	0.54%
27	Mineral supplement	8	0.54%
28	Antidepressants	6	0.40%
29	Antifibrinolytics	5	0.34%

Tab/Fig-6: Distributions of more utilized drugs other than antibiotics in Study, Population

S. No	Medication Name	No. of prescriptions	Percentage
1.	Pantoprazole	164	82%
2	Ondensetron	65	32.5%
3	Paracetamol	64	32%
4	Tramadol	45	22.5%
5	Silymarin	34	17%
6	Mecon plus	23	11.5%
7	Ultracet	21	10.5%
8	Optineuron	21	10.5%
9	Duolin	20	10%
10	Rabeprazole	19	9.5%
11	Rehaptin	17	8.5%
12	Ranitidine	16	8%

Tab/Fig-7: Cost minimization

S. No	Generic Name	Brand Name	Cost (INR)	Present Another brand available in the hospital	Cost (INR)	Percentage Cost Difference
1.	Metronidazole	Metrogyl 500 mg	13.19/inj	Nermit	13/inj	0.19(1.46%)
2.	Meropenam	Meroplan 1gm	3248/vial	Zaxter	3204/vial	44(1.37%)
2.	Meropenam	Meronem 500 mg	1224/inj	Fytopenam	630/ inj	594 (94.28%)
3.	Amikacin	Amiva 500 mg	115/inj	Omnikacin	110/ inj	5(4.5%)
4.	Ceftriaxone	Monocef 1gm	54/inj	Xone	52.35/inj	1.65(3.15%)
4.	Ceftriaxone	Monocef 500 mg	45/vial	Cefaxone	28.15/inj	16.85(59.8%)
5.	Ciprofloxacin	Ciplox 250 mg	3.7/tab	Nircip	2.2/tab	1.5(68.1%)
6.	Cefuroxime	Supacef 1.5 gm	285 /inj	Cetil	248/inj	37(14.91%)
		Ceftum 500 mg	94.8/tab	Cetil	85.65/tab	9.15(10.68%)
		Ceftum 250 mg	47.8/tab	Cetil	46.17/tab	1.63(3.53%)
7.	Piperacillin +Tazobactam	Piptaz 4.5gm	446/inj	Zosyn	427/inj	19(4.44%)
8.	Amoxicillin	Mox 500mg	6.56/tab	Novom ox	1.59/tab	4.97(312.57%)
9.	Cefoperazone + Salbactam	Cegava 1.5 gm	302.20 /inj	Cefactam forte	150/inj	152.2(101.4%)
9.	Cefoperazone + Salbactam	Magnex 1 gm	570.33/inj	Magtam	165/inj	405.33(245.6%)
10.	Doxycycline	Defidox 100mg	449/inj	Doxific	433/inj	16(3.69%)
11.	Octreotide	Octride 100mcg	550/inj	Otide	423/inj	127(30.02%)
12.	Cefepime	Celrim 1 gm	257.70/inj	Novapime	237/inj	20.7(8.43%)
13.	Ertapenam	Invanz 1 gm	3100/inj	Gerta	2462/inj	638(25.91%)
14.	Imepenam + Cilastatin	Zienam 500mg	1942/inj	lupinem	546/inj	1396(255.6%)
15.	Pantorazole	Pantop 40 mg	50/inj	lanpan	45/inj	5(11.11%)
15.	Pantorazole	Pan 40 mg	6/tab	Glanpan	4.9/tab	1.1(22.44%)
16.	Ondensetron	Emeset 4 mg	12/ inj	Omo	11/Inj	1(9.09%)
16.	Ondensetron	Emeset 8 mg	23.7/inj	Periset	22/inj	1.7(7.72%)
17.	Paracetamol	Dolo 650 mg	1.9/tab	Calpol	0.8/tab	1.1(137.5%)
17.	Paracetamol	Malidens 1 gm	389/inj	Neomal	326/inj	63(19.32%)
18.	Tramadol + Paracetamol	Ultracet	11.2/tab	Trazodac p	5.93 /tab	5.27(88.87%)
19.	Rabeprazole	Razo 20 mg	16.6/tab	Rabihart	6.5/tab	10.1(155.38%)
19.	Rabeprazole	Rabicip 20 mg	88/inj	Rabelan	80/inj	8(10%)
20.	Metadoxine + Silymarin + vit B6 + folic acid + L-Ornithine, L-Aspartate	Rehaptin	30/tab	Heptagon	15.9/tab	14.1(88.6%)
21.	Ranitidine	Rantac 50 mg	3.30/ inj	Raniphar	3.1/ inj	0.29(6.45%)
		Zinetac 150 mg	0.73/tab	Aztec	0.47/tab	0.26(55.31%)
		Zinetac 300 mg	1.47/tab	Renitab	0.87/tab	0.6(68.96%)

DISCUSSION:

The study focused on Drug utilization pattern including prescription analysis, frequently used drugs and gender analysis. Present study discovered that male (65.5%) were more compared to female (34.5%) and these findings are similar to the previous studies [male (50.50%) and female (49.50%)] [1,4]. Cost minimization analysis was done to minimize the economic burden of the patient to treat the health conditions. Cost minimization is generally seen in antibiotics and drugs used for permanent disorders like diabetes and hypertension, also in high-cost drugs [12]. The prevalence rate of pancreatitis was 30 percent and approximately similar trend (26%) have been observed in previous Studies [14]. In this study, it was observed that all the hepatic impaired cases are associated with the precipitating factors such as alcohol, smoking was observed in previous study [15]. In this study, greater than 71 percent of prescriptions are prescribed on brand names. commonly, drug cost savings are increased by the branded product method and patient satisfaction also seen by the decreasing cost of drugs [16,17]. The average number of drugs per prescription was 7.3 higher rates have been observed in previous Studies [18,19]. meropenem is the most expensive drug ordered (accounting for 34.7% of the total antibiotic costs) [20], Ceftriaxone, Ertapenem, Amoxicillin, Rabeprazole, Ranitidine, And Combination Drugs like Tramadol + Paracetamol, Imipenem + Cilastatin, Cefoperazone + Sulbactum are the drugs having the cost of more than 30 percent of total cost should be minimized monetarily. Since India is a developing country, use of generics is one of the brilliant ways to reduce prescription costs. Most of the patients do not accept generics because physicians are habituated in prescribing drugs in brand name. Physicians and health care professionals must know about the cost of drugs because expensive drugs may affect the patient compliance and adherence of the patients. For the usage of meropenem in therapy, physicians approval is mandatory since it comes under the restricted antibiotics [21]. Proton pump inhibitors are commonly used in ICU s for the patient’s prophylaxis and antacid action. Ondansetron is a premedicated drug used in the treatment of hepatic impaired patients. In this study, Cholelithiasis (gallbladder stones) condition is higher in females compared with males. Consumption of alcohol and Smoking are the leading risk factors to ALD and CLD which also leads to multiple organ failure, cirrhosis, fatty liver and hepatitis.

Limitations: As with all usage data, this method does not provide complete information on the cost expenditure of drugs. It does not provide any information on antibiotics usage in critical care patients.

CONCLUSION:

It is concluded that the epidemiological studies of hepatic impairment patients have shown the maximum prevalence of pancreatitis. The prevalence of pancreatitis in this current study was reported as 30.5% (n=61) out of 200 cases. So our study suggests that there is a considerable scope for improving prescribing pattern among the health care system and minimizing the use of antibiotics in order to reduce the risk of antibiotic resistance and ADRs. By performing CMA it is evident that same drug molecule with the same strength varying in costs in different brands which will give similar clinical outcomes. It is concluded that cheaper drugs can be prescribed to reduce the health- economic burden. Finally, it is concluded that our extensive research work suggests that a clinical pharmacologist or clinical pharmacist should be instituted for a better drug prescription, medications utilization control and cost minimization of drugs in a healthcare organization.

ACKNOWLEDGMENT:

I genuinely acknowledge my gratefulness to CH. Manoj kumar M.B.B.S., M.D, FICP, FIACM, FIMSA. Manipal Hospitals, Vijayawada and for his valuable guidance, constant encouragement, support and inspiration throughout the period of research work.

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Received on 17.04.2019 Modified on 23.05.2019

Research J. Pharm. and Tech. 2019; 12(10): 4873-4878.

DOI: 10.5958/0974-360X.2019.00844.8