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Senna Alata Extract

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ORIGINAL ARTICLE

Senna alata (akapulko) Extract versus


Topical Antifungals for Treatment of
Superficial Fungal Skin Infections:
a Systematic Review and Meta-analysis
Erin Jane L. Tababa,1 Rowena Natividad S. Flores-Genuino2 and Charissa Mia D. Salud-Gnilo1
1
Section of Dermatology, Department of Medicine, College of Medicine and Philippine General Hospital, University of the Philippines Manila
2
Department of Anatomy, College of Medicine, University of the Philippines Manila

ABSTRACT

Objective. The study aimed to assess the efficacy and safety of Senna alata (akapulko) plant extracts compared
with topical antifungals in the treatment of superficial fungal skin infections.

Methods. A systematic review and meta-analysis of randomized controlled trials that studied patients with
diagnosed cutaneous tinea or dermatophytosis (excluding hair and nail), tinea versicolor, or cutaneous candidiasis, via
microscopy or culture, and compared the efficacy and safety of S. alata (akapulko) extract versus topical antifungals.
Two authors independently screened titles and abstracts of merged search results from electronic databases
(The Cochrane Skin Group Specialized Register, CENTRAL, MEDLINE, EMBASE (January 1990 to December
2011), Health Research and Development Information Network (HERDIN), and reference lists of articles), assessed
eligibility, assessed the risk of bias using the domains in the Cochrane Risk Bias tool and collected data using a
pretested Data extraction form (DEF). Meta-analyses were performed when feasible.

Results. We included seven RCTs in the review. There is low certainty of evidence that S. alata 50% lotion is as
efficacious as sodium thiosulfate 25% lotion (RR 0.91, 95% CI, 0.79 to 1.04; 4 RCTs, n=216; p=0.15; I2=52%) and
high quality evidence that S. alata cream is as efficacious as ketoconazole (RR 0.95, 95% CI, 0.82 to 1.09; 1 RCT,
n=40; p=0.44) and terbinafine cream (RR 0.93, 95% CI, 0.86 to 1.01; 1 RCT, n=150; p=0.09) in mycologic cure.
For adverse effects, there is very low certainty of evidence of increased harm with S. alata 50% lotion compared
to sodium thiosulfate 25% lotion (RR 1.26, 95% CI, 0.46, 3.44; 2 RCTs, n=120; p=0.65; I2=19%). Adverse effects
were few and mild.

Conclusion. S. Alata 50% lotion may be as efficacious as sodium thiosulfate 25% lotion and is as efficacious as
ketoconazole 2% and terbinafine 1% creams. There is insufficient evidence to compare the safety of S. alata 50%
lotion with sodium thiosulfate 25% lotion.

Key Words: Senna alata, Cassia alata, akapulko, skin fungal infections, dermatophytosis, tinea versicolor, pityriasis
versicolor, candidiasis, systematic review, meta-analysis.

Introduction

Superficial fungal skin infections are prevalent in


tropical countries, and are commonly caused by pathogenic
Corresponding author: Erin Jane L. Tababa, MD dermatophytes (Trichophyton spp., Epidermophyton spp., and
Section of Dermatology Microsporum spp.), and normal skin commensals such as
Department of Medicine Malassezia spp. and Candida albicans. Dermatophytes are
Philippine General Hospital
University of the Philippines Manila
keratinase-producing fungi that are capable of invading and
Taft Avenue, Manila 1000, Philippines reproducing within the keratinized tissue of hair, nails, and
Email: erintababa@gmail.com skin.1 These may be transmitted via contact with infected

44 ACTA MEDICA PHILIPPINA VOL. 54 NO. 1 2020


Akapulko for the Treatment of Superficial Fungal Infections

humans, animals, or through exposure with contaminated OBJECTIVE


soil.2 Tinea versicolor (also known as pityriasis versicolor) is
caused by lipophilic Malassezia yeasts, which are normal skin This review aimed to assess S. alata’s efficacy and safety
commensals.3 Candida albicans is also part of the normal flora compared with other topical antifungal drugs as treatment
of the skin, but may cause cutaneous candidiasis particularly for superficial fungal infections.
in immunocompromised individuals.4,
Dermatophytosis, particularly tinea corporis, is one METHODS
of the 10 most common skin conditions at the Philippine
General Hospital’s Section of Dermatology. Based The Cochrane Collaboration methods20 and the
on the Health Information System of the Philippine PRISMA21 statement were followed in this systematic review.
Dermatological Society last 2017, dermatophytosis is the
2nd most common diagnosis seen among both new and old Data Sources
patients.5 It is extremely pruritic, highly contagious, and The authors conducted a search of electronic databases
the treatment can be lengthy and costly. Tinea versicolor (from inception to September 2014), namely: Cochrane Skin
is usually asymptomatic; however, the skin discoloration Group Specialized Register, Cochrane Central Register of
and highly recurrent course pose cosmetic concerns Controlled Trials (CENTRAL), EMBASE, MEDLINE,
for the patient. Lastly, although candidiasis is rarely and Health Research and Development Information Network
associated with significant morbidity in healthy hosts, it (HERDIN). We searched for unpublished trials and ongoing
may become persistent and disseminate systemically in trials using ClinicalTrials.gov and contacted authors and
immunocompromised individuals.6 organizations. We also searched grey literature, references
There are several treatment options for tinea versicolor of included studies, and hand-searched relevant journals
and dermatophytosis. These include keratolytic agents like ( Journal of the Philippine Dermatological Society 1992-
selenium sulfide, propylene glycol, and salicylic acid, which 2013) for potential studies. The following search terms were
act by facilitating removal of affected skin.7 Drugs that work used “Senna alata,” “Cassia alata,” “senna,” “cassia,” “akapulko,”
by inhibiting the cytochrome p450-dependent conversion dermatophyt*, tinea, candidiasis, moniliasis, and candida. All
of lanosterol to ergosterol, such as sodium thiosulfate and relevant randomized controlled trials regardless of language
ketoconazole, disrupt fungal cell membrane and subsequent and status of publication were included.
leakage of cellular contents.8 Terbinafine, an allylamine, Two authors (RG, ET) independently assessed the titles
inhibits squalene epoxidase, the enzyme necessary for the and abstracts of retrieved trials from the search for eligibility
conversion of squalene to lanosterol, thus preventing synthesis for inclusion in the review. When the titles and abstracts
of ergosterol.2 were not enough to decide on eligibility of the trial, the full
Senna alata (L.) Roxb. (syn. Cassia alata) (family report was retrieved to make a decision. If information in
Leguminosae/Fabaceae) or candle bush is an indigenous full report is still not complete, the author was contacted to
plant of central America and known in the Philippines clarify unclear items. A single failed eligibility criterion was
as akapulko.9 S. alata has long been purported to have enough to exclude the trial. Disagreements were resolved
antifungal property and has been studied in several clinical by discussion.
trials regarding its effect on superficial fungal infections such
as dermatophytosis and tinea versicolor.10–14 In vitro studies Study Selection
showed that crude methanol and ethanol extracts of S. We included all relevant RCTs regardless of language,
alata, inhibit growth of Trichophyton rubrum, Microsposrum and status of publication that compared S. alata extract,
canis, and Candida albicans.15,16 According to an in vitro from any part of the plant, with allylamines, azoles, or non-
study, anthraquinone aglycones and anthraquinone specific antifungals as treatment for patients with diagnosed
aglycosides, identified through thin layer chromatography dermatophytosis, cutaneous candidiasis or tinea versicolor
of crude ethanol extracts, are responsible for S. alata’s via direct microscopy. Only the first phase of cross-over
antifungal activity.17 RCTs was included. We excluded studies involving other
S. alata is one of the ten medicinal plants approved for species of Senna and studies with other components
use by the Philippines’ Department of Health. The plant is combined with S. alata extract. Trials were included if they
readily accessible throughout the Philippines, commonly reported the following primary outcomes: percentage of
known to the layperson as a household treatment for skin participants with mycologic clearance defined as a negative
fungal diseases, and a cheaper alternative to the more KOH mount, and percentage of participants who develop
costly azoles and allylamines (leading drugstore, 93 php per adverse/side effects to treatment. Secondary outcome
15 gram tube).18,19 Although there are numerous studies measures were percentage of participants with clinical
available, treatment effects are uncertain. A systematic review resolution of lesions as evaluated by outcome assessor, and
was done in order to collate existing data regarding efficacy percentage of participants who reported clinical resolution
and safety of S. alata as an antifungal. of symptoms.

VOL. 54 NO. 1 2020 ACTA MEDICA PHILIPPINA 45


Akapulko for the Treatment of Superficial Fungal Infections

Data Extraction and Quality Assessment 119 records 3 additional records


Two reviewers independently extracted data using a identified through identified through
pretested data extraction form, and assessed risk of bias using database searching other sources
the Cochrane Collaboration Risk of Bias tool20 from the
included studies. Disagreements between the two authors
were resolved through discussion or a third author. Original
authors of study reports were contacted to ask details of 63 records after
missing data or items needing clarification. duplicates removed
Data was pooled for studies which were clinically
homogenous. RevMan 5 was used to generate summary 63 full text records/ 54 full text records/
tables and graphs. For dichotomous outcomes, risk ratio and abstracts screened abstracts excluded
95% confidence intervals were used, while for continuous
outcomes, mean difference and SD were used. We attempted
to do intent-to-treat analysis by analyzing non-compliant
2 articles were
participants or protocol violators in the group they were excluded. One was
randomized to, regardless of how the original authors not a randomized
analyzed them. Missing data (e.g., participants lost to follow- controlled trial. One
up who did not have any outcome assessments at relevant compared S. alata with
time points) were excluded from the main analysis (available 9 articles assessed a placebo, and not a
case analysis). for eligibility known antifungal drug.
Heterogeneity was assessed using visual inspection of
the forest plots to check for overlapping confidence intervals.
7 studies included in
We also computed for chi-square test for heterogeneity at qualitative synthesis
10% level of significance, and I2 statistic was also computed.
If I2 value was >50%, heterogeneity was assessed to be
significant, and if >75%, it was assessed to be substantial. 7 studies included in
If significant heterogeneity existed, random effects model quantitative synthesis
was used; otherwise, fixed effects model was used. When (meta-analysis)
significant heterogeneity existed, subgroup analysis was done
to determine the possible cause of heterogeneity. Figure 1. Study flowchart.

RESULTS Overall quality assessment shows that majority of studies


were low risk for bias for all domains except for selective
Out of 119 records via database searching and 3 reporting domain where majority were moderate to high
additional records via hand searching, 59 duplicates were risk of reporting bias due to unclear or different definition of
excluded, leaving 63 records for screening of titles and cure outcomes (Figure 2).
abstracts. After assessing full reports and abstracts of nine Only three studies had at least one domain with high
potentially relevant studies for eligibility, two studies were risk of bias (Figure 3).
excluded (Appendix 1) and seven studies were included in
qualitative and quantitative analyses (Figure 1). Primary Outcome Measures
The seven included studies are described in Appendix
2. Four RCTs (461 patients) compared S. alata 50% lotion Mycologic cure
versus sodium thiosulfate (STS) 25% lotion as treatment for Four trials that compared S. alata 50% lotion with STS
tinea versicolor.10,11,14,22 One study (150 patients) compared S. 25% lotion showed that the two treatments were equally
alata cream of unknown concentration against 1% terbinafine efficacious for mycologic cure in tinea versicolor (RR 0.91,
cream as treatment for tinea versicolor.23 One study (48 95% CI, 0.79, 1.04; p=0.15) (Figure 4).10,11,14,22  The presence
patients) investigated an unknown concentration of S. alata of significant heterogeneity (I2=52%) may be attributed
cream against ketoconazole cream as treatment for cutaneous to a longer treatment period, and significant number of
fungal infections and tinea versicolor.13 One study was dropouts in one study.22
conducted in a prison (67 inmates) and compared 3 different Two individual studies noted no significant difference in
kinds of herbal soaps with antifungal properties (3% S. alata mycologic cure comparing S. alata cream with ketoconazole
soap; 5% Erythrophleum guineense; 5% Aframomum melegueta + cream as treatment for dermatophytosis or tinea versicolor
Pipers guineense + Xylopia aethiopica) to treat tinea versicolor, (RR 0.95, 95% CI 0.82, 1.09; n=40; p=0.44)13 and terbinafine
tinea corporis, scabies, and acne/”bump”.24 We did not identify 1% cream when applied twice daily for two weeks (RR 0.93,
any trials on S. alata for cutaneous candidiasis. 95% CI, 0.86, 1.01; n=150; p=0.09).23

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Akapulko for the Treatment of Superficial Fungal Infections

Adverse effects
Only two studies that compared S. alata 50% lotion
with STS 25% lotion as treatment for tinea versicolor noted
adverse effects.10,14 We were uncertain if S. alata lotion had
more adverse effects than STS lotion (RR 1.26, 95% CI
0.46, 3.44; 2n=120; p=0.65; I2=19%) (Figure 5).10,14 The most
common adverse effect for both treatments was pruritus. No
adverse effects were reported by participants in the study
which compared S. alata cream with ketoconazole cream as
treatment for dermatophytosis or tinea versicolor, and in the
study comparing S. alata cream with 1% terbinafine cream as
treatment for tinea versicolor.13,23

Figure 2. Risk of bias graph showing authors’ judgments about risk of bias Figure 3. Risk of bias summary showing
item across all included studies. authors’ judgments about each risk
of bias item for each included study.

Figure 4. S. alata 50% lotion versus STS 25% lotion, Outcome: Mycologic cure.

Figure 5. S. alata lotion versus STS 25% lotion, Outcome: Adverse effects.

VOL. 54 NO. 1 2020 ACTA MEDICA PHILIPPINA 47


Akapulko for the Treatment of Superficial Fungal Infections

Secondary Outcomes (because of high attrition rate) and imprecision due to small
sample size.
Clinical resolution (as reported by outcome assessors) There is high certainty of evidence that S. alata is as
One study (n=36) noted S. alata 50% lotion to be less efficacious as terbinafine for mycologic cure (RR 0.93, 95%
efficacious in clinical resolution of tinea versicolor than STS CI 0.86 to 1.01; 1 RCT, n=150) (Appendix 3: Summary
25% lotion (RR 0.63, 95% CI 0.40, 0.99; p=0.04).10 In one of Findings Table 2) There is high certainty of evidence
other study, it was uncertain whether S. alata cream was that S. alata is as efficacious as ketoconazole for mycologic
less efficacious than ketoconazole cream (RR 0.37, 95% CI cure (RR 0.95, 95% CI 0.82 to 1.09, 1 RCT, n=40) but low
0.02, 8.5; n=40; p=0.53) in achieving complete clearance of certainty of evidence that it is less efficacious for clinical cure
lesions of dermatophytosis and tinea versicolor.13 (RR 0.37, 95% CI 0.02 to 8.5; 1 RCT, n=40) (Appendix 3:
One study compared S. alata soap with two antifungal Summary of Findings Table 3.
soaps (Erythrophleum soap and Aframomum soap) in patients Lastly, there is very low certainty of evidence that S. alata
diagnosed with either tinea versicolor or tinea corporis. It soap is as efficacious as Erythrophleum soap (RR 1.15, 95%
was uncertain whether S. alata soap was more efficacious CI 0.65 to 2.06; 1 RCT, n=35), and more efficacious than
than Erythrophleum soap (RR 1.15, 95% CI 0.65, 2.06; n=35; Aframomum soap (RR 1.94, 95% CI 0.91 to 4.13; 1 RCT,
p=0.63), but there was a trend that it was more efficacious n=37) for mycologic cure. The evidence was downgraded
than Aframomum soap (RR 1.94, 95% CI 0.91, 4.13; n=37; twice due to significant risk of bias from lack of blinding of
p=0.09).24 participants and personnel, lack of pre-specified objectives or
outcomes, and a high number of dropouts.
DISCUSSION
Conclusions
This review included seven RCTs with 460 participants,
mostly patients with tinea versicolor, done in the Philippines This review suggests that S. alata lotion may be as
(5/7), medium-sized (median sample size=98), and efficacious as STS 25% lotion in the treatment of tinea
conducted in the 1990s to 2000s (6/7). The paucity of RCTs versicolor. Adverse effects were few and mild for both
using S. alata is quite striking considering that it is one of treatments and it is unclear whether there is a risk for
the ten medicinal plants recommended by the Department greater adverse effects due to S. alata lotion. Based on single
of Health in the Philippines. Four of the seven included studies, S. alata lotion may be as efficacious as terbinafine
trials used STS lotion as control. The World Health and ketoconazole creams.
Organization lists sodium thiosulfate as one of the topical
treatments for tinea versicolor.25 It acts as a keratolytic, Implications for research
enabling the removal of stratum corneum affected by There is a need for more adequately-sized RCTs with
dermatophytes, and as a fungistatic, particularly against good follow-up comparing S. alata with standard topical
Malassezia furfur, but its mechanism is unknown.26,27 Of antifungal drugs in the treatment of tinea versicolor,
note, current guidelines (NICE, UpToDate) and textbooks cutaneous dermatophyte infections, and candidiasis.
recommend topical antifungals such as azoles, allylamines,
selenium sulfide, and zinc pyrithione as treatment for Ethics review approval
superficial fungal infections.2,28,29 Although the goal of University of the Philippines-Philippine General
this review is to determine the efficacy of S. alata against Hospital (UP-PGH) Expanded Hospital Research Office
superficial fungal infections, majority of the studies focused (EHRO), October 2015 (2015-10-07-058)
on tinea versicolor, which is caused by yeasts. In addition, only
two, small-sized studies compared S. alata with established Study registration
antifungals: ketoconazole and terbinafine. UP Manila-Research Grants Administration Office,
There is low certainty of evidence that S. alata is as January 2018 (RGAO-2018-0014)
effective as STS 25% lotion for mycologic cure (RR 0.91,
95% CI 0.79 to 1.04; 4 RCTs, n=216) but less effective Statement of Authorship
for clinical cure (RR 0.63, 95% CI 0.40 to 0.99, 1 RCT, All authors participated in data collection and analysis,
n=36) (Appendix 3: Summary of Findings Table 1). The and approved the final version submitted.
evidence was downgraded due to a high risk for attrition
bias, as well as high heterogeneity between studies probably Author Disclosure
since one study had a longer treatment period. In terms of All authors declared no conflict of interest.
adverse effects, there is very low certainty of evidence that
S. alata has greater risk of harm than STS 25% lotion (RR Funding Source
1.26, 95% CI 0.46 to 3.44; 2 RCTs, n=120; I2=19%). The This paper was self-funded.
evidence was downgraded twice due to the high risk of bias

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Akapulko for the Treatment of Superficial Fungal Infections

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APPENDICES
Appendix 1. Characteristics of excluded studies
Study ID Reason for exclusion
Damodaran 199430 Not an RCT
Oladele 201031 Comparator was placebo

Appendix 2. Characteristics of included studies


Study ID Participants Intervention Control Outcome/s
Valdez-Eusebio, 98 patients with tinea S. alata 50% lotion (+) Control: STS 25% lotion Mycologic cure on KOH mount;
199022 versicolor; dermatology (-) Control: placebo Clinical activity: scaling and
clinic; Philippines BID for 6 wks. erythema were assessed separately;
BID for 6 wks. Adverse effects
De Dios-Torralba, 60 patients with tinea S. alata 50% lotion STS 25% lotion Mycologic cure on KOH
199314 versicolor; dermatology mount; Clinical activity: scaling
clinic; Philippines BID for 4 wks. BID for 4 wks. and erythema were assessed
separately; Cure (negative KOH
mount and disappearance of
scaling+erythema); Adverse effects
Reyes, 199311 174 patients with tinea S. alata 50% lotion (+) Control: STS 25% solution Mycologic cure on KOH mount;
versicolor; dermatology (-) Control: placebo Clinical activity: scaling and
clinic, Philippines BID for 4 wks. erythema were assessed separately;
BID for 4 wks. Adverse effects
Dofitas, 200110 129 patients with tinea S. alata 50% lotion STS 25% lotion Mycologic cure on KOH mount;
versicolor; dermatology Clinical activity: scaling and
clinic, Philippines BID for 4 wks. BID for 4 wks. erythema were assessed separately;
Adverse effects
De Leon- 150 patients with tinea S. alata cream 1% Terbinafine cream KOH examination recorded as (+)
Pandanan, 200223 versicolor; dermatology or (-) mycologic cure
clinic, Philippines BID for two wks. BID for two wks.
Ting, 200013 48 patients with “cutaneous S. alata cream Ketoconazole cream Clinical resolution of lesions
fungal infection”, (no clearing, partial clearing,
Upper Dicayas Relocation Applied BID for Applied BID for 15 days complete clearing); adverse
Site, Dipolog City, 15 days reaction; KOH smear
Zamboanga del Norte
Oladele, 201224 67 patients with “superficial S. alata soap Control 1: Erythrophleum 5% Did not specify any outcome
fungal skin infections” w/w soap measure
Ilesa Prison, Nigeria Lather and bathe Control 2: Xylopia 5% w/w soap
with soap BID Control 3: placebo soap
for 4 wks.
Lather and bathe with soap BID
for 4 wks.
STS – Sodium thiosulfate; BID – Twice daily

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Akapulko for the Treatment of Superficial Fungal Infections

Appendix 3. Summary of Findings Table 1


50% Senna alata lotion compared to 25% Sodium Thiosulfate lotion for tinea versicolor
Patient or population: tinea versicolor
Setting: Dermatology clinic
Intervention: 50% Senna alata lotion
Comparison: 25% Sodium Thiosulfate lotion
Anticipated absolute effect* (95% CI) No. of Certainty of
Relative effect
Outcome Risk with 25% Sodium Risk with 50% participants the evidence Comments
(95% CI)
Thiosulfate lotion Senna alata lotion (studies) (GRADE)
Mycologic Cure assessed with:
95 per 100
86 per 100 RR 0.91 216 ⨁⨁◯◯
Potassium hydroxide (KOH) smear (75 to 99) (0.79 to 1.04) (4 RCTs)1,2,3,4 LOW 4,a,b
Adverse Effects
9 per 100
11 per 100 RR 1.26 120 ⨁◯◯◯
(4 to 31) (0.46 to 3.44) (2 RCTs)1,3 VERY LOW c,d
Clinical Cure
90 per 100
57 per 100 RR 0.63 36 ⨁⨁◯◯
(36 to 89) (0.40 to 0.99) (1 RCT)4 LOW 4,e,f
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect
of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is
a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
Explanations:
a. High risk for attrition bias. Sensitivity analyses revealed a soft conclusion for three studies. One study did not indicate number of dropouts per
treatment arm.
b. High heterogeneity due to one study with longer treatment period and significant number of dropouts.
c. Sensitivity analysis of one study reveals a soft conclusion, while another study only indicated the number of participants who completed the trial,
hence a sensitivity analysis cannot be performed.
d. Confidence intervals are very wide and crossed both significant benefit (RR>1.25) and harm (RR<0.75).
e. High risk for attrition bias. Sensitivity analysis reveals a soft conclusion.
f. Confidence interval is wide and crossed harm (RR<0.75).
1. De Dios-Torralba, 1993
2. Reyes, 1996
3. Dofitas, 2001
4. Valdez-Eusebio, 1996

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Akapulko for the Treatment of Superficial Fungal Infections

Appendix 3. Summary of Findings Table 2


Senna alata cream compared to Ketoconazole cream for tinea versicolor
Patient or population: tinea versicolor
Setting: Dermatology clinic
Intervention: Senna alata cream
Comparison: Ketoconazole cream
Anticipated absolute effect* (95% CI) No. of Certainty of
Relative effect
Outcome Risk with Risk with participants the evidence Comments
(95% CI)
Ketoconazole cream Senna alata cream (studies) (GRADE)
Mycologic Cure
100 per 100
95 per 100 RR 0.95 40 ⨁⨁⨁⨁
(82 to 100) (0.82 to 1.09) (1 RCT)1 HIGH
Clinical Cure
5 per 100
2 per 100 RR 0.37 40 ⨁⨁◯◯
(0 to 40) (0.02 to 8.50) (1 RCT)1 LOW a
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect
of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is
a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
Explanations:
a. Confidence intervals are very wide and crossed both significant benefit (RR>1.25) and harm (RR<0.75).
1. Ting. 2000

Appendix 3. Summary of Findings Table 3


Senna alata cream compared to 1% Terbinafine cream for dermatophytosis or tinea versicolor
Patient or population: dermatophytosis or tinea versicolor
Setting: Dermatology clinic
Intervention: Senna alata cream
Comparison: 1% Terbinafine cream
Anticipated absolute effect* (95% CI) No. of Certainty of
Relative effect
Outcome Risk with 1% Risk with participants the evidence Comments
(95% CI)
Terbinafine cream Senna alata cream (studies) (GRADE)
Mycologic Cure
97 per 100
91 per 100 RR 0.93 150 ⨁⨁⨁⨁
(84 to 98) (0.86 to 1.01) (1 RCT)1 HIGH
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect
of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is
a possibility that it is substantially different
Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect
Explanations:
1. De Leon-Pandanan, 2002

52 ACTA MEDICA PHILIPPINA VOL. 54 NO. 1 2020

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