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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 9  |  Issue : 3  |  Page : 153-158

Study of delayed treatment perspective of snake bites and their long-term effects in a tertiary care hospital in balgalkot district of Karnataka


Department of Internal Medicine, Bowring and Lady Curzon Hospital, Bengaluru, Karnataka, India

Date of Submission19-Oct-2020
Date of Decision15-Mar-2021
Date of Acceptance05-Apr-2021
Date of Web Publication16-Jul-2021

Correspondence Address:
Dr. C N Mohan
#312/A 6th Main, 4th Block, 3rd Stage, Basaveshwara Nagar, Bengaluru - 560 079, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajim.ajim_78_20

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  Abstract 


Background: Snakebite is an acute life-threatening and time limiting medical emergency. Alternative and traditional methods of cure are barriers to early treatment which results in considerable delay in coming to the hospital. This study was done to assess the clinical profile and to identify long-term perspective of snake bites in patients who presented to the hospital beyond 6 h of snake bite. Methodology: This descriptive study was conducted over 18 months that included 45 patients with alleged history of snake bite of which 15 had delayed presentation, 6 h after snake bite. A detailed history, clinical examination and investigations were monitored for any complications during treatment and follow-up to look for delayed complications. Results: The clinical profile and outcome were different among patients presenting beyond 6 h and within 6 h, cellulitis (46.66% vs. 33.33%), bleeding manifestations (46.66% vs. 50%), neurological manifestations (33.33% vs. 33.33%), AKI (33.33% vs. 16.66%), respiratory failure requiring ventilatory support (33.33% vs. 10%), and mortality (20% vs. none). Delayed complications observed in patients with delayed presentation on long-term follow-up were ulceration including knee amputation, chronic kidney disease, psychiatric disturbances, and musculoskeletal symptoms. Conclusion: The acute complications were significantly higher with delayed presentation and delayed complications that are often overlooked which contributes to significant morbidity and suffering. The general population needs to be educated regarding the available treatment strategies and significance of seeking early medical attention for better treatment outcome and to reduce morbidity and mortality both short term and long term.

Keywords: Acute kidney injury, anti-snake venom, delayed treatment, snake bite


How to cite this article:
Mahendra M, Mujtaba M, Mohan C N, Ramaiah M. Study of delayed treatment perspective of snake bites and their long-term effects in a tertiary care hospital in balgalkot district of Karnataka. APIK J Int Med 2021;9:153-8

How to cite this URL:
Mahendra M, Mujtaba M, Mohan C N, Ramaiah M. Study of delayed treatment perspective of snake bites and their long-term effects in a tertiary care hospital in balgalkot district of Karnataka. APIK J Int Med [serial online] 2021 [cited 2021 Jul 29];9:153-8. Available from: https://www.ajim.in/text.asp?2021/9/3/153/321663




  Introduction Top


Snake bite in India is considered as the “Curse of Almighty” and snakes are considered as messengers of God. Snake bites may be poisonous or nonpoisonous and even among poisonous bites the amount of toxin injected depends on the species of snakes. Russell's viper, kraits and cobras are among the most important biting snake species in India, yet other often unidentified species also represent a threat.[1]

Snakebite is a neglected tropical disease affecting poor farmer communities.[2] Snake bite poisoning is often under-reported, and there is limited accurate data on the global burden of snakebites. The high estimates suggest that there are 5.5 million bites, 1.8 million envenoming and 94,000 deaths annually due to snakebite.[3] India is one among the worst affected countries and it accounts for almost half the total number of annual deaths across the world. India has witnessed 1.2 million snakebite deaths (58,000 per year) from 2000 to 2019, with majority of them are in the age group of 30–69 years. People who reside in densely populated, low altitude, and agricultural areas are at high risk for snake bite and suffered 70% of deaths during the period of 2001–2014.[1]

Acute complications that require immediate medical attention are muscle paralysis that may involve respiratory muscles, bleeding disorders that can result in fatal hemorrhage, acute kidney injury and severe local tissue destruction that can cause permanent disability and limb amputation, therefore antivenom treatment should be given as soon as it is indicated.[2]

Delayed complications at the site of snake bite include, loss of tissue may result from sloughing or surgical debridement of necrotic areas or amputation: Chronic ulceration, infection, osteomyelitis or arthritis may persist causing severe physical disability, malignant transformation may occur in skin ulcers after a number of years (Marjolin's ulcer), chronic kidney disease (renal failure) may occur following bilateral cortical necrosis, chronic panhypopituitarism or diabetes insipidus after Russell's viper is also reported, chronic neurological deficit is seen in patients who survive intracranial hemorrhages and thromboses, abnormalities in the electrocardiography and conduction abnormalities may occur, delayed psychological features such as depression and anxiety, impaired functioning, posttraumatic stress disorder, and unexplained residual physical disability were reported and chronic musculoskeletal disabilities such as swelling, muscle wasting, stiff joints, reduced muscle power, impaired balance, fixed deformities, and chronic nonhealing ulcer.[4]

Most deaths and serious consequences due to snake bites are preventable by early initiation of anti-snake venom (ASV). Snake antivenoms are mandated to be part of any primary health care package where snake bites occur. Variations in the demography and species of snakes, under-reporting of snake bite cases, poisonous or nonpoisonous, use of traditional or herbal treatments and lack of access to health-care facilities or availability of appropriate treatment are among the major reasons as to why the patient seek medical advice late.[5]

Most of the snakebite patients admitted are not followed up once acute effects are resolved. Although some acute pathological effects of envenoming might completely resolve within a few days of the bite, other pathological effects or their consequences may last for months or years.[6],[7],[8] However, due to the lack of follow-up clinically and in research studies, the long-term effects of snake envenoming are poorly defined. In addition, some effects, such as the psychological effects resulting from the snakebite, are likely to have a delayed onset.[9] This study was done to assess the clinical profile of patients coming to the hospital after 6 h of snake bite and also to study the complications including both acute and delayed complications. The study aimed to summarize long-term perspectives of snake bites and identify the knowledge gaps in documentation in nonmetropolitan cites and district.


  Methodology Top


The study was conducted in the inpatient wards of Departments of General Medicine and Paediatrics in S. Nijalingappa Medical College and Hanagal Shri Kumareshwara Hospital and Research Centre, Bagalkot, Karnataka. After obtaining the institutional ethical committee clearance, patients were selected according to the inclusion and exclusion criteria after obtaining a written informed consent. A detailed history regarding the snake bite, including the time and site of the bite, type of snake, immediate systemic manifestations, and history of treatment received from outside, were taken from the patient or from the bystanders. Patients were classified into two groups based on early treatment within 6 h of treatment and delayed treatment more than 6 h after snake bite.

Based on the previous study conducted by Patil SL and Kaveri BV, considering proportion of hemotoxic venom snake bites “P” as 46.1%, and using the formula, n = (DEFF × Np (1-p))/((d2/Z21-α/2 × (N-1) +p × (1-p)) sample size was calculated to be 44.17–45.7 sample size calculation was done using open epi software version 2.3.1. (CDC, Atlanta, Georgia, USA).

The data were collected and analyzed and statistical analysis was done using SPSS version 16.0. The results of the two groups, those who received early treatment and the other group who received delayed treatment were compared using Chi-square/Fisher's exact test for discrete variables and independent t-test for continuous variables. The complications were recorded and appropriate management was given as per protocol management plan in the hospital. Most of the patients were followed up until recovery during hospitalization or death, patients who survived were followed up to look for development of any delayed complications and appropriately treated. Long-term follow-up was done with difficulty in the background of the education levels and distance from the center.


  Results Top


A total of 45 patients were included in the study with a history of snake bite admitted from December 2016 to May 2018. The majority belonged to the age group of 26–45 years constituting about 46.66%, with mean age of study participant being 33 years.

Early and delayed treatment depending on the time of presentation to the hospital had different presentation of symptoms and signs and the parameters of laboratory evidence. The significant laboratory parameters were prothrombin time, serum creatinine and the number of the ASV vials used with the duration of the treatment for recovery [Table 1].
Table 1: Comparison of means of various continuous variables among early and delayed treatment

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Subanalysis of those presenting to the hospital 6 h after snake bite (delayed treatment) were analyzed which included 15 cases out of the 45 patients, 8 (53.33%) were male and 7 (46.67%) female. Mean age group was 32.6 years, majority belonged to age group of 26–45 years (46.66%), followed by 46–65 years (40.0%) and rest (13.4%) belonged to the age group of more than 65 years [Figure 1].
Figure 1: Age distribution of study population in delayed treatment

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About 10 (66.66%) presented to the hospital between 6 and 12 h after bite, 2 (13.33%) within 12–24 h and 3 (20.0%) of them presented 24 h after the bite. Seven (46.67%) patients had viper bite, 5 (33.33%) were bitten by cobra and the other 3 (20.0%) patients did not know the type of the snake. Foot was the most common site of bite, in 12 (80.0%), followed by hand in 3 (20.0%) of them. Majority of the bites were in the night time (86.66%), 2 (13.33%) had got bitten in the day time; all of them reported that they were bitten by the snake outside the home like in the farm or in the backyard.

Local swelling and oozing were seen in 10 (66.66%) patients, the most common presenting symptom, all 10 had pain at the site of swelling, 7 had cellulites and 3 had necrosis, followed by bleeding manifestations in 7 (46.66%) patients, of which, 3 (20.0%) of them presented with visible gum bleeding, while, all 7 (46.66%) of them were found to have, whole blood clotting time beyond 20 min and prolonged bleeding time and clotting time, neurological manifestations in the form of ptosis and respiratory muscle paralysis was seen in 5 (33.33%) patients [Table 2]. Ten (66.66%) of them had associated diabetes mellitus, 8 (53.33%) had hypertension, 3 (20.0%) had ischemic heart disease, and 2 (13.33%) had chronic obstructive pulmonary disease. SOFA score was calculated on admission for all patients and this score was monitored in the critical care unit, 5 (33.33%) had increase in the SOFA score from the baseline, within next 48 h, 7 (46.66%) had decrease in the SOFA score from the baseline, whereas the other 3 (20.0%) had no change in the SOFA scores. Five (33.33%) patients were intubated in view of respiratory failure, among them 3 of them were intubated with 2 h of coming to the hospital and the other 2 within 2–12 h. All patients received protocol-based management, ASV requirement was 30 vials in 14 patients and was 20 vials of ASV in 1 patient, injection neostigmine was administered in 5 patients, 5 (33.33%) of them underwent fasciotomy, 5 (33.33%) required renal replacement therapy in view of acute renal failure and anuria, 8 (53.33%) were put on ventilatory support, 5 (33.33%) were initiated on inotropic support in view of septic shock [Figure 2].
Table 2: Clinical presentation among patients admitted to hospital with snake bite in delayed treatment

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Figure 2: Proportion of complications of snake bite in late complications in late presentation

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Mortality rate was 20%, 3 patients succumbed to the complications of snake bite, 2 were male and 1 female, all three had presented to the hospital beyond 24 h, 2 of them were bitten by viper and 1 by cobra, all three required ventilatory support, 2 of them also required renal replacement therapy. The duration of hospital stay, minimum of 12 days and maximum of 20 days. The remaining 12 patients were followed up even after discharge to look for the development of delayed complications, initially every week for a month and for every month for first 6 months and then every 6 months once for next 2 years, 3 (20.0%) developed chronic ulceration in the lower limb, in which one patient underwent left lower limb below knee amputation, chronic kidney disease in 1 (6.66%), psychiatric disturbances like anxiety and depression in 1 (6.66%) and musculoskeletal symptoms like chronic myalgia was seen in 2 (13.33%) patients [Figure 3].
Figure 3: Delayed complications of snake bite

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  Discussion Top


Snake bite is one of the most important public health concerns, especially in tropical countries. In India, despite better understanding of pathogenesis and availability of ASV, snake bite management pose a challenge.[10] The fatalities that are reported usually are attributed to the victim not reaching the hospital in time where definite treatment can be administered or delay in taking appropriate treatment, since, many of them would be taking unscientific alternative medicine.[11] In the current study, we studied the clinical profile, acute complications, outcome variables and delayed complications in patients presenting to the hospital after 6 h of snake bite.

In our study, all the 45 cases of snake bites received ASV while in the same subgroup analysis about 30% cases presented late (>6 h of snake bite), which is slightly higher than the finding in the study of Patil et al.[12] Of the cases presenting late majority, i.e., 46.66% were in the age group of 26–45 years which is the productive age group with a mean age of 33.09 ± 12.84 years which is in accordance the findings of Ahmed et al.[13] with age range of 20–40 years and 53.33% were male, this was comparable to a study done by Saravu et al.,[14] since males are more often involved in outdoor activities. The cause of delayed presentation may be due to varied treatment seeking behavior of the population and also the availability of the health-care facilities and distance need to be travelled in the remote places.

Viper snake bite was more commonly seen in present study with associated with edema, swelling, oozing by bleeding manifestations, this was consistent with a study done by Saravu et al.[14] and most of them had lower limb bites followed by upper limb bites, was similar to a study done by Bhalla et al.[15] All 15 (100.0%) subjects who presented late in the total study of 45 received ASV, 33.33% patients underwent fasciotomy in view of compartment syndrome, 33.33% patients were initiated on hemodialysis for acute renal failure and 53.33% were on ventilatory support whereas Bhalla et al. noted that 9.2% and 25.0% patients required hemodialysis and ventilatory support.[15]

Patil et al.[12] in his study concluded that delay in hospitalization is associated with poor prognosis and increased mortality rate due to vascular complications or consumptive coagulopathy, renal failure, and respiratory failure which is in accordance with our study findings which showed higher proportion of those with delayed treatment had increased bleeding time, clotting time, and prolonged prothrombin time among which hypotension and bleeding time were significantly associated with the delayed treatment (P < 0.05). Majority of those with delayed treatment had impaired renal function tests (35.5%), electrolyte imbalance (35.7%), acute renal failure (71.4%), respiratory distress (53.3%), and 100.0% had death. Acute renal failure, respiratory distress, and death were significantly associated with the delayed treatment (P < 0.05) [Table 3] and [Figure 3].
Table 3: Outcome differences between early and late treatment

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Higher proportion of those with delayed treatment required fasciotomy, dialysis, ventilator support and among those, requirement of dialysis and ventilator support were significantly associated with the delayed treatment (P < 0.05) which is in accordance with Patil et al.[12] who also showed late admission >6 h after envenomation was associated with ARF requiring dialysis and spreading cellulitis while a study done by Saravu et al. showed that the mean duration of hospital stay was 9.62 days in patients receiving delayed treatment.[16]

Delayed complications like 3 (20.0%) developed chronic ulceration in the lower limb, in which one patient underwent left lower limb below knee amputation, chronic kidney disease in 1 (6.66%), psychiatric disturbances like anxiety and depression in 1 (6.66%) and musculoskeletal symptoms like chronic myalgia 2 (13.33%), were noted in patients who were followed up after discharge, where as a study done by Jayavardhana et al. migraine like syndrome in 46 (5.6%); musculoskeletal disorders such as pain, local swelling, muscle weakness, deformities, contractures, and amputations were found in 26 (3.2%); visual impairment in 21 (2.6%); acute kidney injury in 4 (0.5%); skin blisters at the bite site in 5 (0.6%); psychological distress in 2 (0.2%); hemiplegia in 1 (0.1%); right-sided facial nerve palsy in 1 (0.1%); paresthesia over bite site in 1 (0.1%); generalized shivering in 1 (0.1%); and chronic nonhealing ulcer in 1 (0.1%).[15]

Mortality rate was 20% in the present study with all the deaths occurring among delayed complications and none in early presenters, a study done by Patil et al. concluded that patients presenting late to the hospital following snake bite had significantly high mortality rates (100%). The mean duration of hospital stay among patients who recovered was 15 days.

Clinically, detectable endocrine effects are rarely reported during the acute stage of snake envenoming, but in the present study, we could not record parameters in the follow-ups. In few snakebite survivors who had no clinically detectable hypopituitarism during the acute stage, chronic/delayed hypopituitarism may clinically manifest later as deficiency of cortisol, growth hormone, thyroxine and testosterone (in males).[7],[17],[18] Two studies have summarized 36 previous cases on hypopituitarism in snake envenoming.[7],[18] Intracranial hemorrhage can occur in envenoming by snakes that cause venom induced consumption coagulopathy, including many vipers and Australasian elapids. In the majority of cases, intracranial hemorrhage in combination with severe coagulopathy is fatal, but some patients may survive with permanent neurological sequelae. Blindness and visual impairment are rarely reported following snakebites and are most commonly associated with secondary effects of envenoming. Cortical blindness has been reported in a patient with a Russell's viper bite (Daboia russelii), due to an ischemic stroke.[19] Permanent neurological injury from hypoxic encephalopathy is an important long-term effect of snake envenoming. Respiratory paralysis or cardiac arrest can both result in hypoxia and multiorgan failure resulting in an early death, but some patients survive with significant neurological impairment. However, many of these effects recorded in the literature were not recorded in the present study probably due to lack of knowledge in recognition of symptoms by the patients or the lack of effects in the species of the snakes which are specific to the geographical areas.

The range of clinical effects and their severity in snake envenoming are unique for individual snake species. Therefore, accurate species identification is essential in clinical and epidemiological studies. This can be done by either identification of the snake specimen by a herpetologist or specific venom detection enzyme-linked immunosorbent assay.[20] Most of the studies that describe the long-term effects of snakebite did not have accurate species authentication, which has limited the interpretation of the results. Cohort studies that document the acute stage of envenoming must have accurate case-authentication and active follow-up of patients on regular intervals to provide a detailed picture of the epidemiology and the clinical consequences of the long-term effects of snake envenoming

Even in developed settings, long-term issues related to envenoming in snakebite victims are poorly addressed or reported. The few existing studies of the long-term effects of snake envenoming are based on selected patient groups for follow-up, hence do not provide the true picture of the burden. Some studies have described long-term effects of snake envenoming by relating a disability to a previous snakebite, based on the patient interpretations, which might be biased. The community-based studies on the long-term effects of snake envenoming are useful in understanding the burden of long-term effects of snake envenoming in general.

Limitations of the study were small sample size, subgroup of late presentation is also small in the study. Generalization to population cannot be made because of hospitalization data. Species identification done by history and subject to errors and there is lack of long-term follow-up by the dedicated staff.


  Conclusion Top


Viper bites are associated with more long-term complication in the delayed treatment group in the present study. A protocol-based treatment exist for management of snake bite as per the regional differences and acute and long term of the complications can be prevented by early initiation of treatment, creating awareness in rural and suburbans populations for treatment. The delayed complications if overlooked maybe associated with significant morbidity and mortality. It is important to closely follow-up patients who are discharged. The socioeconomic burden resulting from the physical and psychological consequences of delayed and long-term effects of snake envenoming is enormous in poor resource settings. Modern treatment is still not available for many snakebite victims in the rural tropics and the epidemiology, clinical effects, consequences and socioeconomic impact of snakebite are still understood poorly. Many of the hospitalized and treated patients for the snakebite need to be followed up for 6 weeks at least to recognize delayed complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Suraweera W, Warrell D, Whitaker R, Menon G, Rodrigues R, Fu SH, et. al. Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study. Elife. 2020;9:e54076.  Back to cited text no. 1
    
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Isbister GK. Snakebite doesn't cause disseminated intravascular coagulation: coagulopathy and thrombotic microangiopathy in snake envenoming. Semin Thromb Hemost 2010;36:444-51.  Back to cited text no. 3
    
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Warrell DA. Guidelines for the Management of Snake-Bites. Guidelines for the Management of Snake-Bites. WHO; 2010.Available from: http://apps.searo.who.int/PDS_DOCS/B4508.pdf. [Last accessed on 2018 Jul 14].  Back to cited text no. 4
    
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World Health Organization. Snakebite Envenoming. Fact Sheets; 2018. Available from: http://www.who.int/news room/fact sheets/detail/ snakebite envenoming. [Last accessed on 2020 Oct 19].  Back to cited text no. 5
    
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Herath HM, Wazil AW, Abeysekara DT, Jeewani ND, Weerakoon KG, Ratnatunga NV, et al. Chronic kidney disease in snake envenomed patients with acute kidney injury in Sri Lanka: A descriptive study. Postgrad Med J 2012;88:138-42.  Back to cited text no. 6
    
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Antonypillai CN, Wass JA, Warrell DA, Rajaratnam HN. Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: First case report from Sri Lanka, a review of the literature and recommendations for endocrine management. QJM 2011;104:97-108.  Back to cited text no. 7
    
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Jayawardana S, Gnanathasan A, Arambepola C, Chang T. Chronic musculoskeletal disabilities following snake envenoming in Sri Lanka: A population-based study. PLoS Negl Trop Dis 2016;10:e0005103.  Back to cited text no. 8
    
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Williams SS, Wijesinghe CA, Jayamanne SF, Buckley NA, Dawson AH, Lalloo DG, et al. Delayed psychological morbidity associated with snakebite envenoming. PLoS Negl Trop Dis 2011;5:e1255.  Back to cited text no. 9
    
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Singh S, Singh G. Snake Bite: Indian Guidelines and Protocol. Med Update API 2013;94:424-6.  Back to cited text no. 10
    
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Sitprija V. Snakebite nephropathy. Nephrology (Carlton) 2006;11:442-8.  Back to cited text no. 11
    
12.
Silva A, Hlusicka J, Siribaddana N, Waiddyanatha S, Pilapitiya S, Weerawansa P, et. al. Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests. PLoS neglected tropical diseases. 2020;14:e0008914.  Back to cited text no. 12
    
13.
Saravu K, Somavarapu V, Shastry AB, Kumar R. Clinical profile, species-specific severity grading, and outcome determinants of snake envenomation: An Indian tertiary care hospital-based prospective study. Indian J Crit Care Med 2012;16:187-92.  Back to cited text no. 13
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14.
Ahmed SM, Nadeem A, Islam MS, Agarwal S, Singh L. Retrospective analysis of snake victims in Northern India admitted in a tertiary level institute. J Anaesthesiol Clin Pharmacol 2012;28:45-50.  Back to cited text no. 14
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Jayawardana S, Arambepola C, Chang T, Gnanathasan A. Long-term health complications following snake envenoming. J Multidiscip Healthc 2018;11:279-85.  Back to cited text no. 15
    
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Mao YC, Liu PY, Chiang LC, Lai CS, Lai KL, Ho CH, et al. Naja atra snakebite in Taiwan. Clin Toxicol (Phila) 2018;56:273-80.  Back to cited text no. 16
    
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Warrell DA, Phillips RE, Moore RA, Burke CW. Acute and chronic pitutary failure resembling Sheehan's syndrome following bites by Russell's viper in Burma. Lancet 1987;330:763-7.  Back to cited text no. 17
    
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Shivaprasad C, Aiswarya Y, Sridevi A, Anupam B, Amit G, Rakesh B, et al. Delayed hypopituitarism following Russell's viper envenomation: A case series and literature review. Pituitary 2019;22:4-12.  Back to cited text no. 18
    
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de Silva U, Sarathchandra C, Senanayake H, Pilapitiya S, Siribaddana S, Silva A. Hyponatraemia and seizures in Merrem's hump-nosed pit viper (Hypnale hypnale) envenoming: A case report. J Med Case Rep 2018;12:213.  Back to cited text no. 19
    
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