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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 3  |  Page : 253-262

To compare the efficacy of oral terbinafine alone against the combination of oral terbinafine and intense pulsed light (IPL) in difficult to treat tinea patients


Department of Dermatology, MGM Medical College & Hospital, Aurangabad, Maharashtra, India

Date of Submission24-Dec-2020
Date of Acceptance12-Jun-2021
Date of Web Publication03-Sep-2021

Correspondence Address:
Dr, Suraj Pawar
Department of Dermatology, MGM Medical College & Hospital, MGM Campus, N-6, CIDCO, Aurangabad, Maharashtra.
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mgmj.mgmj_95_20

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  Abstract 

Background: Dermatophytosis is a major health problem in developing countries, with their increase in resistance patterns toward various antifungals being the main reason for concern. Aim: To compare the efficacy of oral terbinafine alone against the combination of oral terbinafine and intense pulsed light (IPL) in difficult-to-treat patients with tinea. Materials and Methods: Patients were divided into two groups, A and B. Group A was given oral terbinafine  mg twice a day for two months. Group B was given oral terbinafine  mg twice a day and IPL once every 15 days for a total of two months. Patients were assessed every 15 days till two months and every one month for three months after the completion of treatment for any recurrences. Results: Among group A, out of 40 patients, 32 patients showed complete cure while only 8 showed a partial cure. Among group B, out of 40 patients, 28 patients showed complete cure while 12 showed a partial cure. Recurrence among group A was 9 patients at the end of 5 months while it was 11 in group B. Conclusion: Even though there is no statistically significant difference between the cure rate of both the groups, terbinafine alone is found to be superior clinically.

Keywords: Intense pulsed light (IPL), terbinafine, tinea


How to cite this article:
Pawar S, Deshmukh AR. To compare the efficacy of oral terbinafine alone against the combination of oral terbinafine and intense pulsed light (IPL) in difficult to treat tinea patients. MGM J Med Sci 2021;8:253-62

How to cite this URL:
Pawar S, Deshmukh AR. To compare the efficacy of oral terbinafine alone against the combination of oral terbinafine and intense pulsed light (IPL) in difficult to treat tinea patients. MGM J Med Sci [serial online] 2021 [cited 2021 Sep 21];8:253-62. Available from: http://www.mgmjms.com/text.asp?2021/8/3/253/325550




  Introduction Top


Dermatophytosis is still a general public health problem.[1],[2],[3] The dermatophytes are the most common fungal infections of the skin and they affect the majority of the population, with their prevalence being high worldwide.[4] Dermatophytes are a group of fungi infecting the keratinized tissues of the body (skin, hair, and nail). They infect the stratum corneum in the epidermis.[5]

Worldwide, superficial mycosis appears to be the most common mycotic infection. At least 10% of the world’s population has dermatophyte infection.[2] A higher incidence was reported in males in India. Overcrowding, poverty, and poor personal hygiene are the risk factors for dermatophytosis.[6] The type and frequency of dermatophytosis may vary with time, living standards, and also due to preventive measures such as personal hygiene.[7]

Dermatophytes can be classified into three groups based on their genera: Trichophyton (which causes infections of skin, hair, and nails), epidermophyton (which causes infections on skin and nails), and microsporum (which causes infections on skin and hair). These can be classified as anthropophilic, zoophilic, and geophilic based on the mode of transmission. Based on the affected site, they can be classified clinically into tinea cruris (involves groin), tinea corporis (involves body), tinea capitis (involves head), tinea faciei (involves face), tinea barbae (involves beard), tinea manuum (involves hand), tinea pedis (involves foot), and tinea unguium (involves nail).[8]

Superficial mycosis can be treated with a variety of drugs such as Terbinafine, Itraconazole, and Griseofulvin. Terbinafine has a very good mycological and pharmacokinetic profile that inhibits enzyme squalene epoxidase, thus inhibiting ergosterol synthesis and it is available easily with very few side effects. This has resulted in it becoming the first drug of choice for the treatment of tinea. It is given in a dose of  mg once daily for two weeks. The cure rate of terbinafine in the past was more than 90% at the earlier mentioned doses.[9]

Nowadays, there is emerging resistance to terbinafine, with a decrease in drug concentration being the mechanism for the same. This factor is responsible for a large number of relapses and treatment failures. However, it is found that terbinafine at high doses ( mg once daily) is very effective and safe against dermatophytosis, which has reduced the incidence of relapse and treatment failure.[10]

There is an increase in the number of recurrent tinea infections in our clinical practice. During the past 15 years, there has been an increase in the proportion of dermatophytoses failing to respond to routine therapy. It becomes very essential to try new modalities in this kind of rapidly spreading fungal infection.[11]

Difficult-to-treat tinea is seen in a patient who has applied topical antifungals and topical steroids and taken systemic antifungals for a minimum period of one month and still disease is not cured or either cured and recurred. Hence, the present study was conducted to study the efficacy and safety of terbinafine and IPL in these difficult-to-treat dermatophytoses.

There are limited options available for the systemic treatment of dermatophytosis; patients often require prolonged treatment, which adds to the cost factor. We found on a review of the literature a study by Dr. Roma Agostino et al. at the University of Rome, which showed the efficacy of IPL in the treatment of onychomycosis.[12]

IPL is a device that has non-laser light sources along with a high intensity that is using a high output flash lamp and it produces a broad wavelength output of noncoherent light, in the range of 500–1200nm. Light pulses generated by most devices are produced by bursts of electrical current passing through a xenon gas-filled chamber.[13] The lamp output is then directed toward the distal end of the handpiece, which, in turn, releases the energy pulse onto the surface of the skin via a quartz block or sapphire.[13]


  Materials and methods Top


This was a prospective, parallel-group randomized open-label study. The present study was done at the Department of Dermatology, Venereology, and Leprosy of MGM Medical College and Hospital, Aurangabad, India with a study duration of one year. The study was started after obtaining approval from the Institutional Ethics Committee. All patients presenting with dermatophytes manifestation attending the outpatient department were assessed properly to check whether they fall into difficult-to-treat criteria. The nature of the study was well explained to patients in a language that they understand, and written consent was obtained from them.

Inclusion criteria

  1. Patients with difficult-to-treat tinea


  2. At least five patches/plaques of tinea


  3. Age more than 18 years


Exclusion criteria

  1. Patients with tinea cruris or onychomycosis


  2. Patients with hypersensitivity to terbinafine


  3. Pregnant/breastfeeding women


  4. When sites affected by the tinea are superinfected, that is, impetigo or herpes simplex


  5. Preexisting dermatological disease such as eczema, psoriasis, and recurrent herpes simplex virus


  6. Active erosion or ulcer over lesions of tinea


  7. Patients with a history of convulsions


  8. Previous history of photosensitivity or sun allergy


  9. History of consumption of retinoid or photosensitizing medication within the past one year


Sample size was calculated as



where, N = sample size

P = prevalence = 0.75

Z = confidence interval = 1.96

D = allowable error = 9.5%



Thus, sample size was taken as 80, and this was divided into two groups of 40 each.

All these patients were divided into two groups of 40 each by random number table into groups A and B. Group A was the comparator group, and group B was the intervention group. In group A, the selected 40 patients were given oral terbinafine  mg twice daily for a total duration of two months. During the course, patients were followed up every 15 days. During every visit, patients were assessed for the following parameters: erythema, scaling, itching, and skin scraping for fungus with 10% KOH. Fungal culture, however, was not performed as we diagnosed patients on a clinical basis alongside the KOH mount on each visit. All these parameters were assessed on a four-point scale as absent, mild, moderate, and severe. After two months of complete treatment, patients were followed up every one month for a total period of three months.

In group B, all 40 patients were given IPL every 15 days for a total of two months. The 530nm filter was used with proper fluence (11–13 J/cm2). Two such passes were given. Treatment was repeated every two weeks for a total period of two months. Oral terbinafine  mg twice daily was given along with IPL for a total of two months. During the course, patients were followed every 15 days, the same as group A. After two months of complete treatment, follow-up was taken every one month for a total period of three months. Each patient was assessed properly during follow-up while considering the same parameters as group A. Patients in both groups were not given any topical antifungals, as the patients included in our study were having extensive areas involved, which would have been cumbersome and also added to the cost to the patient.

An objective method of scoring for both the groups: (Mycological cure)

  • Grade 0 (score 8–10): no improvement


  • Grade 1 (score 2–7): partial cure


  • Grade 2 (score 0–1): complete cure


The collected data were coded and entered into a Microsoft Excel sheet. The data were analyzed by using Statistical Package for Social Sciences (SPSS) version 20.0 software. The result was obtained in a tabular and graphical format. Comparison of data was done statistically by using the chi-square test. A P value of less than 0.05 indicates a significant difference.


  Observations and results Top


The distribution of patients according to age among both the groups is presented in [Table 1]. It was observed that the majority of patients in group A and group B were in the age group of 21–30 years (32.5% and 40%), respectively. There was no significant difference in age distribution in both groups (P = 0.5747). [Table 2] shows the distribution of patients according to sex among both groups. It was observed that the majority of patients in both group A and group B were male, 55% and 65% respectively. There was male dominance in both groups.
Table 1: Age distribution among two groups

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Table 2: Sex distribution among two groups

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[Table 3] contains the distribution of patients according to the efficacy of group A (only oral terbinafine therapy). At the first visit, it was observed that the majority of patients had severe itching (30 patients; 75%), as compared with 19 (47.5%) patients with no itching at the fifth visit with statistical significance (P < 0.05). Similarly, at the first visit, severe erythema among 13 (32.5%) patients was observed; as compared with 32 (80%) patients with no erythema at the fifth visit with statistical significance (P < 0.05).
Table 3: Efficacy of only oral terbinafine therapy

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Similarly, at the first visit, moderate scaling among 29 (72.5%) patients was observed, as compared with 36 (90%) patients with no scaling at the fifth visit with statistical significance (P < 0.05).

The distribution of patients according to the efficacy of group B (IPL and oral terbinafine therapy) is presented in [Table 4]. At the first visit, it was observed that the majority of patients had severe itching (25 patients; 62.5%), as compared with 14 (35%) patients with no itching at the fifth visit with statistical significance (P < 0.05). Similarly, at the first visit, severe erythema among 13 (32.5%) patients was observed, as compared with 28 (70%) patients with no erythema at the fifth visit with statistical significance (P < 0.05).
Table 4: Efficacy of IPL therapy and oral terbinafine

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Similarly, at the first visit, moderate scaling among 20 (50%) patients was observed, as compared with 36 (90%) patients with no scaling at the fifth visit with statistical significance (P < 0.05).

[Table 5] contains a comparison of the efficacy of group A and group B. It was observed that group A and group B showed no statistically significant difference as compared with itching, erythema, and scaling at all visits (P > 0.05). [Table 6] provides a comparison of skin scraping for fungus positive group A and group B. It was observed that group A and group B showed no significance, as compared with skin scraping at the first visit (P > 0.05). At the fourth and fifth visit, group B showed more patients, 20% and 7.5% respectively, as compared with 5% and 0% in group A with statistical significance (P < 0.05).
Table 5: Comparison of efficacy among both groups

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Table 6: Skin scraping for fungus positivity in both groups

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[Table 7] shows a comparison of mycological cure among group A and group B. It was observed that group A showed a more complete cure (80%) compared with group B (70%), with no statistical significance (P > 0.05). [Table 8] explains a comparison of recurrence at the end of five months among group A and group B. It was observed that group A showed less recurrence (22.5%) compared with group B (27.5%), with no statistical significance (P > 0.05).
Table 7: Comparison of mycological cure among two groups

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Table 8: Comparison of recurrence at the end of five months among two groups

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[Figure 1][Figure 2][Figure 3][Figure 4] show a clinical photograph of patients of group A, which is photographed at the first visit and then photographed after two-month therapy with oral terbinafine  mg once a day.
Figure 1: Group A: Oral terbinafine for two months. A, First visit. B, After two months of oral terbinafine

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Figure 2: Group A: Oral terbinafine for two months. A, First visit. B, After two months of oral terbinafine

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Figure 3: Group A: Oral terbinafine for two months. A, First visit. B, After two months of oral terbinafine

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Figure 4: Group A: Oral terbinafine for two months. A, First visit. B, After two months of oral terbinafine

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[Figure 5][Figure 6][Figure 7][Figure 8] show a clinical photograph of patients of group B, which is photographed at the first visit and then photographed after two-month therapy with oral terbinafine with IPL once in 15 days.
Figure 5: Group B: Two months of oral terbinafine with IPL. A, First visit. B, After two months of oral terbinafine with IPL

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Figure 6: Group B: Two months of oral terbinafine with IPL. A, First visit. B, After two months of oral terbinafine with IPL

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Figure 7: Group B: Two months of oral terbinafine with IPL. A, First visit. B, After two months of oral terbinafine with IPL

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Figure 8: Group B: Two months of oral terbinafine with IPL. A, First visit. B, After two months of oral terbinafine with IPL

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  Discussion Top


Mycotic infections are worldwide in distribution, with superficial mycoses being more prevalent in tropical and subtropical countries, including India, where heat and moisture play an important role in promoting the growth of these organisms. Superficial skin infections caused by dermatophytes resulting in local inflammation are common in humans. In recent years, there is a worldwide increase in people getting affected by these tinea infections.

The distribution of patients according to age among both groups showed that the majority of patients in group A and group B were in the age group of 21–30 years (32.5% and 40%), respectively. There was no significant difference in age distribution in both groups (P = 0.5747).

It was also observed that the majority of patients in both group A and group B were male, 55% and 65%, respectively. There was male dominance in both groups. Bhatia et al.[14] studied the efficacy of terbinafine and observed an average age of 34.78 years among the patients with 107 males (66.8%). This finding has been endorsed by various studies in India and abroad[15],[16] owing to physical outdoor labor, their nature of work, and frequent interactions with different people of society. Xu et al.[17] compare the efficacy and safety of combined treatment with a long-pulsed 1064-nm Nd: YAG laser and oral terbinafine with those of either treatment alone. They obtained the mycological clearance rate and the clinical clearance rate of the total three groups at 4, 8, 12, 16, and 24 weeks. No significant differences in the gender and age of the patients were observed. Huang et al. found that 420-nm IPL is effective in inhibiting the growth of Trichophyton rubrum.[18]

Efficacy of only oral terbinafine therapy

After the distribution of patients according to the efficacy of group A (only oral terbinafine therapy), at the first visit, it was observed that the majority of patients had severe itching (30 patients; 75%) as compared with 19 (47.5%) patients with no itching at the fifth visit, with statistical significance (P < 0.05).

Similarly, at the first visit, severe erythema among 13 (32.5%) patients was observed, as compared with 32 (80%) patients with no erythema at the fifth visit with statistical significance (P < 0.05). Similarly, at the first visit, moderate scaling among 29 (72.5%) patients was observed; as compared with 36 (90%) patients with no scaling at the fifth visit with statistical significance (P < 0.05).

Bhatia et al.[14] studied the efficacy of terbinafine in the treatment of tinea corporis and tinea cruris and observed that there was a statistically significant improvement in erythema, scaling, and pruritus at six months.

Efficacy of IPL + oral terbinafine therapy

The distribution of patients was done according to the efficacy of group B (IPL + oral terbinafine therapy). At the first visit, it was observed that the majority of patients had severe itching (25 patients; 62.5%), as compared with 14 (35%) patients with no itching at the fifth visit with statistical significance (P < 0.05).

Similarly, at the first visit, severe erythema among 13 (32.5%) patients was observed, as compared with 28 (70%) patients with no erythema at the fifth visit with statistical significance (P < 0.05). Similarly, at the first visit, moderate scaling among 20 (50%) patients was observed, as compared with 36 (90%) patients with no scaling at the fifth visit with statistical significance (P < 0.05).

In 2010, Kozarev and Vizintin[19] reported MCRs of 95.8% and 100% after laser treatment for three and six months, respectively. Another study demonstrated an MCR of 87.5% after the second or third session of laser treatment.[20]

The biological and physical effects of laser treatment on dermatophytes have been discussed in several studies but remain uncertain. Some researchers have proposed that the effectiveness of laser treatment results from the photothermolytic effect of heating both the nail and the fungus.[21] Other hypotheses are that nonspecific heating of tissues results in vasodilatation and an increase in circulation, which stimulates immunological processes,[22] and that the laser induces the formation of free radicals and influences cellular metabolic reactions.

It was observed that group A and group B showed no statistical difference, as compared with itching, erythema, and scaling at all visits (P > 0.05). It was observed that group A and group B showed no statistical difference, as compared with skin scraping at the first visit (P > 0.05). At the fourth and fifth visit, group B showed more patients, 20% and 7.5%, respectively, as compared with 5% and 0% in group A, with statistical significance (P < 0.05). Shi et al.[23] evaluated the efficacy of fractional carbon dioxide (CO2) laser treatment combined with terbinafine and observed that this treatment for six months was an effective and safe method for the treatment of onychomycosis.

Mycological cure

The distribution of patients according to mycological cure among patients of group A (only oral terbinafine therapy) at two months showed that the majority of patients had complete cure (80%) followed by partial cure (20%). The distribution of patients according to mycological cure among patients of group B (IPL + oral terbinafine therapy) at two months showed that the majority of patients had complete cure (70%) followed by partial cure (30%).

The comparison of recurrence at the end of five months among group A and group B showed that group A showed less recurrence (22.5%) compared with group B (27.5%), with no statistical significance (P > 0.05). It was also observed that group A showed a more complete cure (80%) compared with group B (70%), with no statistical significance (P > 0.05).

The most common side effects that occur with terbinafine are nausea, indigestion, dyspepsia, gastritis, headache, and rash; rarely, it causes blood pathologies and hepatitis. However, in our study, no side effects such as nausea, headache, and gastritis were seen. During treatment, two patients in group B showed post-inflammatory hypopigmentation due to IPL, of which one resolved on its own till the last follow-up.


  Conclusion Top


The present study concludes that oral terbinafine alone has higher clinical and mycological cure rates as compared with IPL + oral terbinafine. Even the cost of terbinafine is lower compared with IPL, and the failure rate is less. It even becomes very difficult to give IPL over the intertriginous area. Therefore, only oral terbinafine seems to be superior to IPL+ terbinafine in the treatment of tinea.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical consideration

The approval from Institutional Ethical Committee has been obtained from MGM Ethics Committee for Research on Human Subjects vide their letter no. MGM-ECRHS/2017/69 dated October 25, 2017.



 
  References Top

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Emmons CW, Binford CH, Utz JP, Kwon-chung KJ. Medical Mycology. 3rd ed. Philadelphia: Lea & Febiger; 1977. 592 p.  Back to cited text no. 1
    
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Venugopal PV, Venugopal TV. Actinomycotic susceptibility testing of dermatophytes. Ind J Med Microbiol 1993;11:151-4.  Back to cited text no. 4
    
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Crispin JC, Alcocer-Varela J. Rheumatologic manifestations of diabetes mellitus. Am J Med 2003;114:753-7.  Back to cited text no. 5
    
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Djeridane A, Djeridane Y, Ammar-Khodja A. Epidemiological and aetiological study on tinea pedis and onychomycosis in Algeria. Mycoses 2006;49:190-6.  Back to cited text no. 7
    
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Hay RJ, Ashee HR. Mycology. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook’s Textbook of Dermatology. 4 vols. set. 8th ed. United Kingdom: Wilkey-Blackwell; 2010.vol. 2. p. 36.1-93.  Back to cited text no. 8
    
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Hay RJ, Logan RA, Moore MK, Midgely G, Clayton YM. A comparative study of terbinafine versus griseofulvin in “dry type” dermatophyte infections. J Am Acad Dermatol 1991;24:243-6.  Back to cited text no. 10
    
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Agostino R, Valerio P, Mauro M. Onychomycosis Treatment with “Fungus Clinic” IPL device: University of Rome “La Sapienza”—Italy Medical and Surgical Treatment. Milan: Routledge; 1995. Available from: http://mybodyessentials.co.uk/wp-content/uploads/2013/08/Onychomycosis-Treatment-with-Fungus-Clinic-IPL-Device-.pdf. [Last accessed on January 15, 2021].  Back to cited text no. 12
    
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Bhatia A, Kanish B, Badyal DK, Kate P, Choudhary S. Efficacy of oral terbinafine versus itraconazole in treatment of dermatophytic infection of skin—A prospective, randomized comparative study. Indian J Pharmacol 2019;51:116-9.  Back to cited text no. 14
[PUBMED]  [Full text]  
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Huang H, Huang M, Lv W, Hu Y, Wang R, Zheng X, et al. Inhibition of Trichophyton rubrum by 420-nm intense pulsed light: In vitro activity and the role of nitric oxide in fungal death. Front Pharmacol 2019; 10:1143.  Back to cited text no. 18
    
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Kozarev J, Vizintin Z. Novel laser therapy in the treatment of onychomycosis. J Laser Health Acad2010;2010:1-8. Available from: https://www.laserandhealthacademy.com/media/objave/academy/priponke/novel_laser_therapy_in_treatment_of_onychomycosis.pdf. [Last accessed on January 15, 2021].  Back to cited text no. 19
    
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Shi J, Li J, Huang H, Permatasari F, Liu J, Xu Y, et al. The efficacy of fractional carbon dioxide (CO2) laser combined with terbinafine hydrochloride 1% cream for the treatment of onychomycosis. J Cosmet Laser Ther 2017;19:353-9.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8]



 

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