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The Cochrane Database of Systematic... Jan 2020Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Onychomycosis refers to fungal infections of the nail apparatus that may cause pain, discomfort, and disfigurement. This is an update of a Cochrane Review published in 2007; a substantial amount of new research warrants a review exclusively on toenails.
OBJECTIVES
To assess the clinical and mycological effects of topical drugs and device-based therapies for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers, and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials.
SELECTION CRITERIA
Randomised controlled trials of topical and device-based therapies for onychomycosis in participants with toenail onychomycosis, confirmed by positive cultures, direct microscopy, or histological nail examination. Eligible comparators were placebo, vehicle, no treatment, or an active topical or device-based treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Primary outcomes were complete cure rate (normal-looking nail plus fungus elimination, determined with laboratory methods) and number of participants reporting treatment-related adverse events.
MAIN RESULTS
We included 56 studies (12,501 participants, average age: 27 to 68 years), with mainly mild-to-moderate onychomycosis without matrix involvement (where reported). Participants had more than one toenail affected. Most studies lasted 48 to 52 weeks; 23% reported disease duration (variable). Thirty-five studies specifically examined dermatophyte-caused onychomycosis. Forty-three studies were carried out in outpatient settings. Most studies assessed topical treatments, 9% devices, and 11% both. We rated three studies at low risk of bias across all domains. The most common high-risk domain was performance bias. We present results for key comparisons, where treatment duration was 36 or 48 weeks, and clinical outcomes were measured at 40 to 52 weeks. Based on two studies (460 participants), compared with vehicle, ciclopirox 8% lacquer may be more effective in achieving complete cure (risk ratio (RR) 9.29, 95% confidence interval (CI) 1.72 to 50.14; low-quality evidence) and is probably more effective in achieving mycological cure (RR 3.15, 95% CI 1.93 to 5.12; moderate-quality evidence). Ciclopirox lacquer may lead to increased adverse events, commonly application reactions, rashes, and nail alteration (e.g. colour, shape). However, the 95% CI indicates that ciclopirox lacquer may actually make little or no difference (RR 1.61, 95% CI 0.89 to 2.92; low-quality evidence). Efinaconazole 10% solution is more effective than vehicle in achieving complete cure (RR 3.54, 95% CI 2.24 to 5.60; 3 studies, 1716 participants) and clinical cure (RR 3.07, 95% CI 2.08 to 4.53; 2 studies, 1655 participants) (both high-quality evidence) and is probably more effective in achieving mycological cure (RR 2.31, 95% CI 1.08 to 4.94; 3 studies, 1716 participants; moderate-quality evidence). Risk of adverse events (such as dermatitis and vesicles) was slightly higher with efinaconazole (RR 1.10, 95% CI 1.01 to 1.20; 3 studies, 1701 participants; high-quality evidence). No other key comparison measured clinical cure. Based on two studies, compared with vehicle, tavaborole 5% solution is probably more effective in achieving complete cure (RR 7.40, 95% CI 2.71 to 20.24; 1198 participants), but probably has a higher risk of adverse events (application site reactions were most commonly reported) (RR 3.82, 95% CI 1.65 to 8.85; 1186 participants (both moderate-quality evidence)). Tavaborole improves mycological cure (RR 3.40, 95% CI 2.34 to 4.93; 1198 participants; high-quality evidence). Moderate-quality evidence from two studies (490 participants) indicates that P-3051 (ciclopirox 8% hydrolacquer) is probably more effective than the comparators ciclopirox 8% lacquer or amorolfine 5% in achieving complete cure (RR 2.43, 95% CI 1.32 to 4.48), but there is probably little or no difference between the treatments in achieving mycological cure (RR 1.08, 95% CI 0.85 to 1.37). We found no difference in the risk of adverse events (RR 0.60, 95% CI 0.19 to 1.92; 2 studies, 487 participants; low-quality evidence). The most common events were erythema, rash, and burning. Three studies (112 participants) compared 1064-nm Nd:YAG laser to no treatment or sham treatment. We are uncertain if there is a difference in adverse events (very low-quality evidence) (two studies; 85 participants). There may be little or no difference in mycological cure at 52 weeks (RR 1.04, 95% CI 0.59 to 1.85; 2 studies, 85 participants; low-quality evidence). Complete cure was not measured. One study (293 participants) compared luliconazole 5% solution to vehicle. We are uncertain whether luliconazole leads to higher rates of complete cure (very low-quality evidence). Low-quality evidence indicates there may be little or no difference in adverse events (RR 1.02, 95% CI 0.90 to 1.16) and there may be increased mycological cure with luliconazole; however, the 95% CI indicates that luliconazole may make little or no difference to mycological cure (RR 1.39, 95% CI 0.98 to 1.97). Commonly-reported adverse events were dry skin, paronychia, eczema, and hyperkeratosis, which improved or resolved post-treatment.
AUTHORS' CONCLUSIONS
Assessing complete cure, high-quality evidence supports the effectiveness of efinaconazole, moderate-quality evidence supports P-3051 (ciclopirox 8% hydrolacquer) and tavaborole, and low-quality evidence supports ciclopirox 8% lacquer. We are uncertain whether luliconazole 5% solution leads to complete cure (very low-quality evidence); this outcome was not measured by the 1064-nm Nd:YAG laser comparison. Although evidence supports topical treatments, complete cure rates with topical treatments are relatively low. We are uncertain if 1064-nm Nd:YAG laser increases adverse events compared with no treatment or sham treatment (very low-quality evidence). Low-quality evidence indicates that there is no difference in adverse events between P-3051 (ciclopirox hydrolacquer), luliconazole 5% solution, and their comparators. Ciclopirox 8% lacquer may increase adverse events (low-quality evidence). High- to moderate-quality evidence suggests increased adverse events with efinaconazole 10% solution or tavaborole 5% solution. We downgraded evidence for heterogeneity, lack of blinding, and small sample sizes. There is uncertainty about the effectiveness of device-based treatments, which were under-represented; 80% of studies assessed topical treatments, but we were unable to evaluate all of the currently relevant topical treatments. Future studies of topical and device-based therapies should be blinded, with patient-centred outcomes and an adequate sample size. They should specify the causative organism and directly compare treatments.
Topics: Administration, Topical; Adult; Aged; Antifungal Agents; Female; Humans; Male; Middle Aged; Onychomycosis; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31978269
DOI: 10.1002/14651858.CD012093.pub2 -
Journal of Foot and Ankle Research 2019Onychomycosis, a fungal infection affecting the nail plate, is a common condition often requiring prolonged treatment regimens, with low success rates. Urea is one...
BACKGROUND
Onychomycosis, a fungal infection affecting the nail plate, is a common condition often requiring prolonged treatment regimens, with low success rates. Urea is one treatment option, which is thought to improve the efficacy of topical and oral antifungal agents. Despite a theoretical basis for the use of urea for the treatment of onychomycosis, the evidence-base for this treatment has not been systematically reviewed.
AIM
The purpose of this study was to conduct a systematic literature review to determine the efficacy and safety of urea as a monotherapy and as adjunct therapy, compared to other treatment regimens for onychomycosis.
METHOD
A systematic literature search of ten electronic databases was conducted. Only studies that used microscopy and culture or other validated laboratory-based testing method to confirm the presence of a fungal infection before treatment were included. The outcome measures assessed were efficacy (defined in terms of mycological, clinical and complete cure) and safety (defined as self-reported adverse events).
RESULTS
The systematic search yielded 560 unique studies for review. Of these, only six were eligible for inclusion. All studies were observed to have methodological concerns, most studies consisted of small sample sizes and were difficult to compare given heterogeneity in outcome measures and follow-up time. Despite this, a trend was observed to suggest that urea, when added to topical or oral antifungal treatment regimens, improved efficacy of the treatment.
CONCLUSION
This review suggests that topical urea, as an adjunct to topical and oral antifungal treatment regimens, may improve the efficacy of treatment. However, further research is needed.
Topics: Administration, Cutaneous; Antifungal Agents; Drug Therapy, Combination; Evidence-Based Medicine; Humans; Onychomycosis; Treatment Outcome; Urea
PubMed: 31007722
DOI: 10.1186/s13047-019-0332-3 -
The Cochrane Database of Systematic... Jul 2017Fungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely affected, it can interfere with normal daily activities. Treatment is taken orally or applied topically; however, traditionally topical treatments have low success rates due to the nail's physical properties. Oral treatments also appear to have shorter treatment times and better cure rates. Our review will assist those needing to make an evidence-based choice for treatment.
OBJECTIVES
To assess the effects of oral antifungal treatments for toenail onychomycosis.
SEARCH METHODS
We searched the following databases up to October 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We sought to identify unpublished and ongoing trials by correspondence with authors and by contacting relevant pharmaceutical companies.
SELECTION CRITERIA
RCTs comparing oral antifungal treatment to placebo or another oral antifungal treatment in participants with toenail onychomycosis, confirmed by one or more positive cultures, direct microscopy of fungal elements, or histological examination of the nail.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 48 studies involving 10,200 participants. Half the studies took place in more than one centre and were conducted in outpatient dermatology settings. The participants mainly had subungual fungal infection of the toenails. Study duration ranged from 4 months to 2 years.We assessed one study as being at low risk of bias in all domains and 18 studies as being at high risk of bias in at least one domain. The most common high-risk domain was 'blinding of personnel and participants'.We found high-quality evidence that terbinafine is more effective than placebo for achieving clinical cure (risk ratio (RR) 6.00, 95% confidence interval (CI) 3.96 to 9.08, 8 studies, 1006 participants) and mycological cure (RR 4.53, 95% CI 2.47 to 8.33, 8 studies, 1006 participants). Adverse events amongst terbinafine-treated participants included gastrointestinal symptoms, infections, and headache, but there was probably no significant difference in their risk between the groups (RR 1.13, 95% CI 0.87 to 1.47, 4 studies, 399 participants, moderate-quality evidence).There was high-quality evidence that azoles were more effective than placebo for achieving clinical cure (RR 22.18, 95% CI 12.63 to 38.95, 9 studies, 3440 participants) and mycological cure (RR 5.86, 95% CI 3.23 to 10.62, 9 studies, 3440 participants). There were slightly more adverse events in the azole group (the most common being headache, flu-like symptoms, and nausea), but the difference was probably not significant (RR 1.04, 95% CI 0.97 to 1.12; 9 studies, 3441 participants, moderate-quality evidence).Terbinafine and azoles may lower the recurrence rate when compared, individually, to placebo (RR 0.05, 95% CI 0.01 to 0.38, 1 study, 35 participants; RR 0.55, 95% CI 0.29 to 1.07, 1 study, 26 participants, respectively; both low-quality evidence).There is moderate-quality evidence that terbinafine was probably more effective than azoles for achieving clinical cure (RR 0.82, 95% CI 0.72 to 0.95, 15 studies, 2168 participants) and mycological cure (RR 0.77, 95% CI 0.68 to 0.88, 17 studies, 2544 participants). There was probably no difference in the risk of adverse events (RR 1.00, 95% CI 0.86 to 1.17; 9 studies, 1762 participants, moderate-quality evidence) between the two groups, and there may be no difference in recurrence rate (RR 1.11, 95% CI 0.68 to 1.79, 5 studies, 282 participants, low-quality evidence). Common adverse events in both groups included headache, viral infection, and nausea.Moderate-quality evidence shows that azoles and griseofulvin probably had similar efficacy for achieving clinical cure (RR 0.94, 95% CI 0.45 to 1.96, 5 studies, 222 participants) and mycological cure (RR 0.87, 95% CI 0.50 to 1.51, 5 studies, 222 participants). However, the risk of adverse events was probably higher in the griseofulvin group (RR 2.41, 95% CI 1.56 to 3.73, 2 studies, 143 participants, moderate-quality evidence), with the most common being gastrointestinal disturbance and allergic reaction (in griseofulvin-treated participants) along with nausea and vomiting (in azole-treated participants). Very low-quality evidence means we are uncertain about this comparison's impact on recurrence rate (RR 4.00, 0.26 to 61.76, 1 study, 7 participants).There is low-quality evidence that terbinafine may be more effective than griseofulvin in terms of clinical cure (RR 0.32, 95% CI 0.14 to 0.72, 4 studies, 270 participants) and mycological cure (RR 0.64, 95% CI 0.46 to 0.90, 5 studies, 465 participants), and griseofulvin was associated with a higher risk of adverse events, although this was based on low-quality evidence (RR 2.09, 95% CI 1.15 to 3.82, 2 studies, 100 participants). Common adverse events included headache and stomach problems (in griseofulvin-treated participants) as well as taste loss and nausea (in terbinafine-treated participants). No studies addressed recurrence rate for this comparison.No study addressed quality of life.
AUTHORS' CONCLUSIONS
We found high-quality evidence that compared to placebo, terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis, with moderate-quality evidence of excess harm. However, terbinafine probably leads to better cure rates than azoles with the same risk of adverse events (moderate-quality evidence).Azole and griseofulvin were shown to probably have a similar effect on cure, but more adverse events appeared to occur with the latter (moderate-quality evidence). Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin (low-quality evidence).Only four comparisons assessed recurrence rate: low-quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo, but there may be no difference between them.Only a limited number of studies reported adverse events, and the severity of the events was not taken into account.Overall, the quality of the evidence varied widely from high to very low depending on the outcome and comparison. The main reasons to downgrade evidence were limitations in study design, such as unclear allocation concealment and randomisation as well as lack of blinding.
Topics: Administration, Oral; Adult; Aged; Antifungal Agents; Azoles; Female; Foot Dermatoses; Griseofulvin; Humans; Male; Middle Aged; Naphthalenes; Onychomycosis; Randomized Controlled Trials as Topic; Recurrence; Secondary Prevention; Terbinafine
PubMed: 28707751
DOI: 10.1002/14651858.CD010031.pub2 -
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 -
Emerging Infectious Diseases Sep 2020We conducted a systematic literature review to obtain risk population-based fungal disease incidence or prevalence data from China. Data were categorized by risk factors...
We conducted a systematic literature review to obtain risk population-based fungal disease incidence or prevalence data from China. Data were categorized by risk factors and extrapolated by using most recent demographic figures. A total of 71,316,101 cases (5.0% of the population) were attributed to 12 risk factors and 17 fungal diseases. Excluding recurrent Candida vaginitis (4,057/100,000 women) and onychomycosis (2,600/100,000 persons), aspergillosis (317/100,000 persons) was the most common problem; prevalence exceeded that in most other countries. Cryptococcal meningitis, an opportunistic infection, occurs in immunocompetent persons almost twice as often as AIDS. The pattern of fungal infections also varies geographically; Talaromyces marneffei is distributed mainly in the Pearl River Basin, and the Yangtze River bears the greatest histoplasmosis burden. New host populations, new endemic patterns, and high fungal burdens in China, which caused a huge impact on public health, underscore the urgent need for building diagnostic and therapeutic capacity.
Topics: China; Cost of Illness; Female; Humans; Mycoses; Prevalence; Talaromyces
PubMed: 32818410
DOI: 10.3201/eid2609.200016 -
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 -
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 -
Antimicrobial Resistance and Infection... 2018Identifying the source of an outbreak is the most crucial aspect of any outbreak investigation. In this review, we address the frequently discussed question of whether...
BACKGROUND
Identifying the source of an outbreak is the most crucial aspect of any outbreak investigation. In this review, we address the frequently discussed question of whether (rectal) screening of health care workers (HCWs) should be carried out when dealing with outbreaks caused by gram negative bacteria (GNB).A systematic search of the medical literature was performed, including the Worldwide Outbreak Database and PubMed. Outbreaks got included if a HCW was the source of the outbreak and the causative pathogen was an , ., ., ., , or This was true for 25 articles in which there were 1196 (2.1%) outbreaks due to GNB, thereof 14 HCWs who were permanently colonized by the outbreak strain. Rectal screening of HCWs was helpful in only 2 of the 1196 (0.2%) outbreaks. Instead, the hands of HCWs served as a reservoir for the outbreak strain in at least 7 articles - especially when they suffered from onychomycosis or used artificial fingernails or rings.
CONCLUSION
Due to very weak evidence, we do not recommend rectal screening of HCWs in an outbreak situation with GNB. However, besides a critical review of hand hygiene habits, it might be useful to examine the hands of staff carefully. This measure is cheap, quick to perform, and seems to be quite effective.
Topics: Anti-Infective Agents; Cross Infection; Databases, Factual; Disease Outbreaks; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hand Hygiene; Health Personnel; Hospitals; Humans; Infection Control; Mass Screening
PubMed: 29556377
DOI: 10.1186/s13756-018-0330-4