-
Journal of the American Podiatric... Jun 2021
Background: The efficacy of antifungals for onychomycosis has been determined in randomized controlled trials (RCTs); interestingly their control arms have...
Background: The efficacy of antifungals for onychomycosis has been determined in randomized controlled trials (RCTs); interestingly their control arms have demonstrated some therapeutic effects. These controls constitute either placebos (inert pills) or vehicles (all but the antifungal component of the creams). The objective of this research was to determine (i) whether RCT controls exhibited statistically-relevant efficacy rates (i.e. beyond the "placebo effect"), (ii) whether oral and topical controls differed in their efficacies, and (iii) if the efficacy rates of the controls correlated with those of the active comparator associated with that control.
Methods: RCTs of oral and topical monotherapies for dermatophyte toenail onychomycosis were identified through a systematic literature search. For our meta-analyses of cure rates the double arcsine transformation was used. The N-1 chi squared test was used to determine whether the cure rates significantly differed between topical and oral controls. Correlation was investigated using Kendall rank correlation tests.
Results: The pooled mycological, complete, and clinical cure rates of all control interventions (n = 19 trials) were 9%, 1%, and 6%, respectively. The pooled efficacy rates for oral and topical controls were: mycological cure rate, 7% and 12% (p=0.0016); complete cure rate, 1% for both; and clinical cure rate, 4% and 8%, respectively (p=0.0033). For oral RCTs, the respective cure rates of the active therapies were not correlated with controls. However, for topical RCTs, as the mycological and clinical cure rates of the active therapy increased, so did those of the topical vehicle associated with the active therapy in question, and vice versa.
Conclusions: The topical vehicle cure rates were often higher than the oral placebo cure rates, likely due to the presence of non-antifungal chemicals (e.g. moisturizers, urea) with antifungal and debriding properties, which are not present in oral controls.
.PubMed: 34121113
DOI: 10.7547/20-226 -
Seminars in Arthritis and Rheumatism Apr 2019To determine characteristics of the foot and ankle in people with systemic lupus erythematosus (SLE). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine characteristics of the foot and ankle in people with systemic lupus erythematosus (SLE).
METHODS
Medline, CINAHL, Sports-Discus, Scopus and Cochrane Library databases were searched up to January 2018. Studies reporting foot- and ankle-related outcomes in the following domains were included: vascular, neurological, musculoskeletal, cutaneous (skin and nail) or pain/function. The Quality Index tool was used to assess methodological quality. Where appropriate, odds ratio (OR) and mean difference meta-analyses were conducted for case-control studies; and pooled mean prevalence meta-analyses for studies assessing characteristics in SLE.
RESULTS
Forty-nine studies were included with mean (range) quality scores of 75% (38-100%). Twenty-three studies assessed vascular characteristics, followed by musculoskeletal (n = 16), neurological (n = 11), cutaneous (n = 5) and pain/function (n = 4). Foot and ankle characteristics in people with SLE included impaired vascular supply, abnormal nerve function, musculoskeletal pathology, skin and nail pathology, and pain and functional disability. Twenty-four studies were included in meta-analyses. Pooled OR for abnormal ankle brachial index was 3.08 for SLE compared with controls. Pooled mean difference in brachial-ankle pulse-wave velocity between SLE and controls was significant (161.39 cm/s, P = 0.004). Pooled prevalence was 0.54 for intermittent claudication, 0.50 for Raynaud's phenomenon, 0.28 for chilblains, 0.00 for gangrene, 0.30 for hallux valgus, 0.15 for onychomycosis, 0.76 for history of foot pain, and 0.36 for current foot pain.
CONCLUSION
People with SLE experience a wide range of foot and ankle manifestations. Published research highlights the impact of peripheral arterial disease, peripheral neuropathy, musculoskeletal deformity, skin and nail pathology and patient-reported foot pain and disability.
Topics: Case-Control Studies; Female; Foot Diseases; Foot Joints; Humans; Lupus Erythematosus, Systemic; Male; Pain
PubMed: 30093237
DOI: 10.1016/j.semarthrit.2018.07.002 -
Dermatologic Therapy May 2017The efficacy and safety of amorolfine 5% nail lacquer in combination with systemic antifungal agents in the treatment of the onychomycosis were evaluated. According to... (Comparative Study)
Comparative Study Meta-Analysis Review
The efficacy and safety of amorolfine 5% nail lacquer in combination with systemic antifungal agents in the treatment of the onychomycosis were evaluated. According to our meta-analysis, combination treatment of amorolfine 5% nail lacquer and systemic antifungals can result in higher percentage of complete clearance of onychomycosis. It showed that the experimental combination group was more effective than monotherapy of the systemic antifungals [OR (odds ratio) = 1.97, 95%CI (95% confidence interval) = 1.44-2.69], and no more adverse events happened with the addition of amorolfine 5% nail lacquer (OR = .96, 95%CI = .56-1.63, p = .95). This effect strengthens the fact that amorolfine 5% nail lacquer in combination with systemic antifungal agents was better than the monotherapy of systemic antifungals like itraconazole and terbinafine.
Topics: Administration, Topical; Antifungal Agents; Drug Therapy, Combination; Humans; Itraconazole; Lacquer; Morpholines; Naphthalenes; Onychomycosis; Terbinafine
PubMed: 28097731
DOI: 10.1111/dth.12457 -
The British Journal of Dermatology May 2012The analysis of comparative efficacy and safety of topical antifungals in the literature is restricted to the treatment of tinea pedis and onychomycosis. Therefore our... (Meta-Analysis)
Meta-Analysis Review
The analysis of comparative efficacy and safety of topical antifungals in the literature is restricted to the treatment of tinea pedis and onychomycosis. Therefore our objective was to evaluate and compare the efficacy and safety of topical antifungals used in the treatment of dermatomycosis, we performed a comprehensive search for randomized controlled trials (RCTs) in the following databases: Medline, Cochrane Central Register of Controlled Trials, EMBASE, Lilacs and International Pharmaceutical Abstracts, we identified studies that compared the use of topical antifungals with other antifungals or with placebo published up to July 2010 in English, Spanish or Portuguese. The quality of reporting was assessed according to the Jadad scale; only studies with a score of 3 or more were included. The outcomes evaluated were mycological cure at the end of treatment, sustained cure, occurrence of adverse events and tolerability, including withdrawals due to adverse events. A total of 104 RCTs satisfied the inclusion criteria, containing a total of 135 comparisons, with 55 out of 120 possible comparisons among the 16 drugs evaluated. Pooled data on efficacy showed that all the antifungals were better than placebo. There were no significant differences among antifungal classes. No differences were found in safety or tolerability in any direct comparison. Sensitivity analysis indicated the robustness of the findings. Our results indicate the clear superiority of topical antifungals over placebo but that there is no consistent difference among classes. Mixed treatment comparisons are necessary to rank antifungals, as direct comparisons among many of them are lacking.
Topics: Administration, Cutaneous; Antifungal Agents; Dermatomycoses; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 22233283
DOI: 10.1111/j.1365-2133.2012.10815.x -
BMC Infectious Diseases Feb 2017Onychomycosis is a highly prevalent disease worldwide. There is no standard test for its diagnosis, which remains costly, wasteful, and is sometimes delayed. The... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Onychomycosis is a highly prevalent disease worldwide. There is no standard test for its diagnosis, which remains costly, wasteful, and is sometimes delayed. The diagnostic tests for this disease are few and discordant. The objective was to evaluate the diagnostic validity, performance, and accuracy of culture, nail clipping with Periodic Acid-Schiff -PAS- staining (biopsy), and direct potassium hydroxide (KOH) examination for the study of onychomycosis.
METHODS
A systematic review was conducted via meta-analysis using 5 databases and 21 search strategies. An ex ante protocol was applied with inclusion and exclusion criteria. Quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool, and the sensitivity, specificity, predictive values, likelihood ratios, diagnostic odds ratios, receiver operating characteristic (ROC) curves, and proportion of correctly diagnosed patients were evaluated with the meta-analysis of studies of evaluations of diagnostic and screening tests (Meta-DiSc) and Epidat using a random effects model.
RESULTS
The efficiency or accuracy of the three tests is influenced by the methodological quality of the studies. These values are lower for KOH and culture and higher for biopsy in moderate quality studies.
CONCLUSION
The diagnostic tests evaluated in this meta-analysis independently showed acceptable validity, performance, and efficiency, with nail clipping with PAS staining outperforming the other two tests.
Topics: Biopsy; Foot Dermatoses; Hand Dermatoses; Humans; Hydroxides; Indicators and Reagents; Nails; Odds Ratio; Onychomycosis; Periodic Acid-Schiff Reaction; Potassium Compounds; ROC Curve; Reproducibility of Results; Sensitivity and Specificity
PubMed: 28222676
DOI: 10.1186/s12879-017-2258-3 -
Cureus May 2024Onychomycosis, a fungal infection of the nails, presents a significant challenge in clinical management due to its chronic nature and resistance to conventional... (Review)
Review
Onychomycosis, a fungal infection of the nails, presents a significant challenge in clinical management due to its chronic nature and resistance to conventional therapies. This study aims to evaluate the efficacy of laser therapy in treating onychomycosis compared to traditional methods such as terbinafine. A systematic review and meta-analysis were conducted to analyze existing literature on the subject. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram illustrates the selection process of studies. Findings suggest that laser therapy demonstrates promising results in the treatment of onychomycosis, with comparable efficacy to terbinafine and fewer adverse effects. Further large-scale randomized controlled trials are warranted to validate these findings and establish laser therapy as a standard treatment option for onychomycosis.
PubMed: 38841013
DOI: 10.7759/cureus.59720 -
Drug Discovery Today Jan 2024Recalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided... (Review)
Review
Recalcitrant nail plate infections can be life-long problems because localizing antifungal agents into infected tissues is problematic. In this systematic review, guided by the SPIDER method, we extracted chemical nail permeation data for 38 compounds from 16 articles, and analyzed the data using quantitative structure-property relationships (QSPRs). Our analysis demonstrated that low-molecular weight was essential for effective nail penetration, with <120 g/mol being preferred. Interestingly, chemical polarity had little effect on nail penetration; therefore, small polar molecules, which effectively penetrate the nail, but not the skin, should be set as the most desirable target chemical property in new post-screen onychomycosis candidate selections.
Topics: Humans; Administration, Topical; Antifungal Agents; Nails; Onychomycosis; Skin; Quantitative Structure-Activity Relationship
PubMed: 38000719
DOI: 10.1016/j.drudis.2023.103844 -
Journal of the European Academy of... Mar 2020Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Onychomycosis is a chronic, fungal infection of the nails. Complete cure remains challenging, but oral antifungal medications have been successful in managing the fungus for a significant proportion of patients. Treatment with these drugs can be continuous or intermittent, albeit the evidence on their relative efficacies remains unclear.
OBJECTIVE
To determine the relative effectiveness and safety of pulse versus continuous administration, of three common oral therapies for dermatophyte onychomycosis, by conducting multiple-treatment meta-analysis.
METHODS
This systematic review and network meta-analysis compared the efficacy (as per mycological cure) and adverse event rates of three oral antifungal medications in the treatment of dermatophyte toenail onychomycosis, namely terbinafine, itraconazole and fluconazole. A total of 30 studies were included in the systematic review, while 22 were included in the network meta-analysis.
RESULTS
The likelihood of mycological cure was not significantly different between continuous and pulse regimens for each of terbinafine and itraconazole. Use of continuous terbinafine for 24 weeks - but not 12 weeks - was significantly more likely to result in mycological cure than continuous itraconazole for 12 weeks or weekly fluconazole for 9-12 months. Rank probabilities demonstrated that 24-week continuous treatment of terbinafine was the most effective. There were no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole and fluconazole. Drug treatments were similar to placebo in terms of their likelihood of producing adverse events.
CONCLUSION
More knowledge about the fungal life cycle and drugs' pharmacokinetics in nail and plasma could further explain the relative efficacy and safety of the pulse and continuous treatment regimens. Our results indicate that in the treatment of dermatophyte toenail onychomycosis, the continuous and pulse regimens for terbinafine and itraconazole have similar efficacies and rates of adverse events.
Topics: Administration, Oral; Antifungal Agents; Fluconazole; Humans; Itraconazole; Onychomycosis; Terbinafine; Treatment Outcome
PubMed: 31746067
DOI: 10.1111/jdv.16101 -
The Journal of Dermatological Treatment Dec 2022Fungal skin and nail infections are common health issues affecting an estimated 10%-20% of the world's population. The antifungal agent terbinafine shows broad-spectrum... (Review)
Review
Fungal skin and nail infections are common health issues affecting an estimated 10%-20% of the world's population. The antifungal agent terbinafine shows broad-spectrum activity against a wide range of fungal species and is commonly prescribed as a first-line treatment for dermatomycoses and onychomycoses. However, owing to insufficient data regarding embryotoxicity and adverse pregnancy outcomes, treatment with terbinafine is currently not recommended in pregnancy and breastfeeding. This systematic review aimed to evaluate the effects of gestational terbinafine exposure on congenital malformations, spontaneous abortions, and adverse pregnancy outcomes. PubMed/MEDLINE, EMBASE, and clinicaltrials.org were searched to retrieve relevant reports up to March 2022. Two investigators independently screened the articles, extracted the data, and performed a quality assessment using the Newcastle-Ottawa Scale. Two cohort and two case-control studies were eligible for inclusion. Overall, the study showed the absence of an increased risk of congenital malformations, spontaneous abortion, preterm birth, small for gestational age, low birth weight, or stillbirth, following systemic or topical terbinafine exposure during pregnancy. In conclusion, the use of systemic and topical terbinafine during pregnancy can be regarded as safe for mothers and unborn children. The current recommendation concerning gestational terbinafine administration should be reconsidered.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Pregnancy Outcome; Abortion, Spontaneous; Terbinafine; Premature Birth; Antifungal Agents
PubMed: 35930463
DOI: 10.1080/09546634.2022.2110837 -
Archives of Dermatology Jun 2002To identify and synthesize the evidence for the efficacy of oral treatments for fungal infections of the toenails. (Comparative Study)
Comparative Study Review
OBJECTIVE
To identify and synthesize the evidence for the efficacy of oral treatments for fungal infections of the toenails.
DESIGN
Systematic review of randomized controlled trials.
INTERVENTIONS
Oral treatments for dermatophyte infections of the toenails.
MAIN OUTCOME MEASURES
Cure confirmed by microscopy and culture results in patients with clinically diagnosed fungal infections. Data relating to the clinical cure rates were also extracted from the trials.
RESULTS
A pooled analysis of 2 trials comparing mycological cure rates from continuous treatment with terbinafine (250 mg/d for 12 weeks) and continuous treatment with itraconazole (200 mg/d for 12 weeks) found a statistically significant difference in 11- and 12-month outcomes in favor of terbinafine (risk difference, -0.23 [95% confidence interval, -0.32 to -0.15]; number needed to treat, 5 [95% confidence interval, 4 to 8]). An analysis of clinical cure rates was not possible because of the diversity of definitions used in researching the effectiveness of oral antifungal drugs for onychomycosis. Only 3 trials gave a clear definition of clinical cure and presented data for these outcomes.
CONCLUSIONS
There is good evidence that a continuous regimen of terbinafine (250 mg/d) for 3 months is the most effective oral treatment for fungally infected toenails. Consensus among researchers evaluating oral antifungal drugs for onychomycosis is needed to establish meaningful definitions of clinical cure. Most trials were funded by the pharmaceutical industry; we found little independent research, and this may have introduced bias to the review.
Topics: Administration, Oral; Antifungal Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Evidence-Based Medicine; Female; Foot Dermatoses; Griseofulvin; Humans; Itraconazole; Ketoconazole; Male; Naphthalenes; Onychomycosis; Prognosis; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Terbinafine; Treatment Outcome
PubMed: 12056964
DOI: 10.1001/archderm.138.6.811