Relative impact of traditional vs. newer oral antifungals for dermatophyte toenail onychomycosis: a network meta-analysis study.

BACKGROUND: There is a paucity of evidence regarding the relative therapeutic efficacy of treatments for onychomycosis. OBJECTIVES: We determined the relative efficacy of monotherapies for dermatophyte toenail onychomycosis with Bayesian network meta-analyses (NMAs). METHODS: We searched PubMed, Scopus, EMBASE (Ovid) and CINAHL to identify studies that investigated the efficacy of monotherapy with oral antifungals for dermatophyte toenail onychomycosis in adults. In this paper, 'regimen' corresponds to a given agent and its dosage. The relative effects and surface under the cumulative ranking curve (SUCRA) values of the various regimens were estimated; evidence quality was assessed at the study level and across networks. RESULTS: Data from 21 studies were used. Our two efficacy-related endpoints were: (i) mycological and (ii) complete cure at 1 year; safety--related endpoints were: (i) 1-year count of any adverse event (AE), (ii) 1-year odds of discontinuation due to any AE, (iii) 1-year odds of discontinuation due to liver issues. Thirty-five regimens were identified; the newer agents among these included posaconazole and oteseconazole. We compared the efficacy of newer regimens with traditional ones like 'terbinafine 250 mg daily for 12 weeks' and 'itraconazole 200 mg daily for 12 weeks. We found that an agent's dosage was associated with its efficacy; for example, the 1-year odds of mycological cure with terbinafine 250 mg daily for 24 weeks (SUCRA = 92.4%) were significantly greater than those of terbinafine 250 mg daily for 12 weeks (SUCRA = 66.3%) (odds ratio 2.62, 95% credible interval 1.57-4.54). We also found that booster regimens can increase efficacy. Our results showed that some triazoles could be more effective than terbinafine. CONCLUSIONS: This is the first NMA study of monotherapeutic antifungals - and their various dosages - for dermatophyte toenail onychomycosis. Our findings could provide guidance for the selection of the most appropriate antifungal agent, especially amid the growing concerns about terbinafine resistance.

Labeled use of efinaconazole topical solution 10% in treating onychomycosis in children and a review of the management of pediatric onychomycosis.

Onychomycosis is a difficult to treat condition whose prevalence is increasing. Until recently, there was no FDA approved antifungal agent for the treatment of onychomycosis in children. Although systemic antifungal agents are effective, their use is restricted by the potential adverse events and drug-drug interactions. There is evidence regarding the safety and efficacy of topical antifungal agents for pediatric onychomycosis. We have summarized the results of a recently published study using efinaconazole topical solution 10% to treat onychomycosis in children and discuss management of pediatric onychomycosis. In a multicenter, open-label phase 4 study, efinaconazole 10% solution was applied topically once daily in children aged 6 to 16 years with mild to severe, culture positive, distal and lateral subungual onychomycosis. Treatment was for 48 weeks with a follow-up at week 52. Pharmacokinetics was performed in a subset of patients. There were 62 patients enrolled in the study. At week 52, the efficacy was mycological cure rate 65% and complete cure rate 40%. All treatment-emergent adverse events (TEAE) were mild to moderate in severity with none resulting in study discontinuation. The only treatment-related TEAE was ingrown toenail. Efinaconazole was detected at low levels in plasma. Efinaconazole topical solution 10% is effective and safe in treating onychomycosis in children age 6 to 16 years and was recently FDA-approved for this indication. The on-label use of other topical agents, tavaborole solution 5% and ciclopirox nail lacquer solution 8% is reviewed. We also briefly discuss the use of oral agents, terbinafine, itraconazole, and fluconazole in pediatric onychomycosis.

The emergence of Trichophyton indotineae: Implications for clinical practice.

Emergence and increase of terbinafine-resistant dermatophytosis led to the identification of Trichophyton mentagrophytes internal transcriber space (ITS) genotype VIII in 2017, later renamed as Trichophyton indotineae and classified as a separate species in 2020. With its suspected origin in South Asia, this novel strain has emerged in Bahrain, Canada, Denmark, Finland, France, Germany, India, Iran, Japan, Russia, and Switzerland, with its spread attributed primarily to travel and migration. Diagnosis using routine mycology laboratory techniques is unable to distinguish T. indotineae from T. mentagrophytes and T. interdigitale; specific identification requires genomic sequencing to identify unique, specific markers. One speculated reason for this recent outbreak is the unrestricted use of topical steroid creams and antifungal agents. Patients with extensive tinea corporis and cruris due to T. indotineae present with inflammatory red plaques in multiple body sites. The majority of these infections prove to be resistant to conventional antifungals, including allylamines and azoles (itraconazole and fluconazole), thus emphasizing the need for antifungal susceptibility testing before treatment initiation and for reassessing in nonresponsive patients. Molecular studies have identified several point mutations in the ERG1 (terbinafine resistance) and ERG11 (azole resistance) genes, which need to be analyzed further. Use of relatively new agents, such as voriconazole and luliconazole, as well as device modalities and combination therapy, could be investigated for recalcitrant T. indotineae infections.

Antifungal resistance in superficial mycoses.

BACKGROUND AND OBJECTIVE: With the widespread use of antifungals to treat superficial mycoses, reports of antifungal resistance are increasing. Antifungal resistance is becoming a public health challenge and needs to be addressed in parallel with antibacterial and antiviral resistance. METHODS: We review the growing resistance of fungal pathogens such as Trichophyton species and the emergence of novel pathogens, including multidrug-resistant strains in superficial mycoses. We also discuss the importance of laboratory diagnosis and antifungal susceptibility testing (AFST) in the management of recalcitrant infections. RESULTS AND CONCLUSIONS: Antifungal resistance can occur naturally or develop over time when fungi are exposed to antifungals. The frequency of terbinafine-resistant Trichophyton isolates is increasing. Opportunistic pathogens such as Aspergillus and Candida species have developed resistance to classic azoles such as itraconazole and fluconazole, and the newer azoles such as posaconazole and voriconazole. Although uncommon, topical antifungals such as efinaconazole and tavaborole have shown to induce resistance in Trichophyton rubrum. The emergence of multidrug-resistant Trichophyton mentagrophytes/interdigitale, Candida auris, and Aspergillus species causing severe infections is highly concerning. Routine AFST should be considered to determine the most effective treatment, especially if there is failure to therapy. Combination treatment of oral and topical antifungals may be a consideration for managing recalcitrant infections.

Onychomycosis in Older Adults: Prevalence, Diagnosis, and Management.

The risk of having onychomycosis increases with age. Data suggest that the prevalence of onychomycosis may be ≥ 20% in subjects aged ≥ 60 years and ≥ 50% in those aged ≥ 70 years. Older males are 2.1 times more prone to onychomycosis than are females. Although most nail dystrophies (approximately 50%) are caused by onychomycosis, proper clinical assessment followed by mycological examination is recommended to exclude other conditions such as nail trauma, lichen planus, and psoriasis. The US FDA-approved onychomycosis treatments are systemic antifungals (terbinafine and itraconazole) for severe onychomycosis and topical antifungals (ciclopirox 8%, efinaconazole 10%, and tavaborole 5%) for mild-to-moderate onychomycosis. Oral fluconazole is used off-label, and itraconazole may be considered for non-dermatophyte onychomycosis. Recently, fosravuconazole was approved in Japan for onychomycosis treatment. Although the treatment options and durations are the same for older patients as for other age groups, a clinical decision should take into account various age-related factors such as comorbidities, polypharmacy, hepatic and renal insufficiency, and noncompliance. Clinicians should also consider possible drug interactions and side effects when choosing a particular antifungal. Since the recurrence rate of onychomycosis is high, older patients should practice sanitization techniques, consider lifestyle changes, and perhaps consider using a topical antifungal as long-term maintenance therapy one to three times per week to prevent the recurrence of onychomycosis or to treat early disease.

Artificial hair implantation for hair restoration.

BACKGROUND: Androgenetic alopecia (AGA) is the most common cause of hair loss in men and women. Artificial hair implantation is considered an alternative treatment when the donor area is depleted or unsuitable for hair transplantation. The use of artificial hair implants remains controversial, particularly because this practice has been banned by the US FDA. OBJECTIVE: To summarize various aspects of artificial hair implantation. METHODS: We discuss the history of artificial hair implantation, development of new biocompatible fibers (Biofibre®, Nido Z-type), patient eligibility for this treatment, implantation technique, follow-up, immune response to the implanted fibers, and post-implantation complications. We performed a methodological quality assessment of the clinical studies that investigated artificial hair implantation using the Canadian Institute of Health Economics (IHE) Quality Appraisal Tool for Case Series (Interventional). RESULTS: Although the studies evaluating the use of artificial hair fibers appear promising, the methodological quality of most of them was between 'poor' and 'fair', due to lack of randomization, absence of control groups, improper study design, and inappropriate outcome measures. CONCLUSIONS: Artificial hair implantation has been received with skepticism among physicians due to the complications reported. Further high-quality research needs to be performed to ascertain the safety and efficacy of artificial hair implantation.

Efficacy of Lasers for the Management of Dermatophyte Toenail Onychomycosis.

BACKGROUND: Onychomycosis is a chronic fungal nail infection caused predominantly by dermatophytes, and less commonly by nondermatophyte molds and Candida species. Onychomycosis treatment includes oral and topical antifungals, the efficacy of which is evaluated through randomized, double-blind, controlled trials for US Food and Drug Administration approval. The primary efficacy measure is complete cure (complete mycologic and clinical cure). The secondary measures are clinical cure (usually ≤10% involvement of target nail) and mycologic cure (negative microscopy and culture). Some lasers are US Food and Drug Administration approved for the mild temporary increase in clear nail; however, some practitioners attempt to use lasers to treat and cure onychomycosis. METHODS: A systematic review of the literature was performed in July of 2020 to evaluate the efficacy rates demonstrated by randomized controlled trials of laser monotherapy for dermatophyte onychomycosis of the great toenail. RESULTS: Randomized controlled trials assessing the efficacy of laser monotherapy for dermatophyte toenail onychomycosis are limited. Many studies measured cure rates by means of nails instead of patients, and performed only microscopy or culture, not both. Only one included study reported mycologic cure rate in patients as negative light microscopy and culture (0%). The combined clinical cure rates in short- and long-pulsed laser studies were 13.0%-16.7% and 25.9%, respectively. There was no study that reported the complete cure rate; however, one did report treatment success (mycologic cure [negative microscopy and culture] and ≤10% clinical involvement) in nails as 16.7%. CONCLUSIONS: The effectiveness of lasers as a therapeutic intervention for dermatophyte toenail onychomycosis is limited based on complete, mycologic, and clinical cure rates. However, it may be possible to use different treatment parameters or lasers with a different wavelength to increase the efficacy. Lasers could be a potential management option for older patients and onychomycosis patients with coexisting conditions such as diabetes, liver, and/or kidney diseases for whom systemic antifungal agents are contraindicated or have failed.

Review of the alternative therapies for onychomycosis and superficial fungal infections: posaconazole, fosravuconazole, voriconazole, oteseconazole.

Terbinafine and itraconazole are the most commonly used oral antifungals to treat onychomycosis and superficial dermatomycoses. Recently, poor response to oral terbinafine has been reported. We have summarized the most appropriate dosing regimens of posaconazole, fosravuconazole, voriconazole, and oteseconazole (VT-1161) to treat onychomycosis and superficial fungal infections. A structured search on PubMed and Google Scholar was conducted. Additionally, the bibliographies of selected articles were searched to identify relevant records. The number of records identified from the searches was 463, with 50 articles meeting the inclusion criteria for review. None of the new azoles are US FDA approved for onychomycosis treatment; however, an increasing number of studies have evaluated these agents. The efficacies (complete cure and mycologic cure) of the antifungal agents for dermatophyte great toenail onychomycosis treatment are terbinafine 250 mg/day × 12 weeks (Phase III trial) (38%, 70%), itraconazole 200 mg/day × 12 weeks (Phase III trial) (14%, 54%), posaconazole 200 mg/day × 24 weeks (Phase IIB) (54.1%, 70.3%), fosravuconazole 100 mg/day ravuconazole equivalent × 12 weeks (Phase III) (59.4%, 82.0%), and oteseconazole 300 mg/day loading dose × 2 weeks (Phase II), followed by 300 mg/week × 10 weeks (maintenance dose) (45%, 70%). Guidelines for monitoring are also presented.

Relative Efficacy of Minoxidil and the 5-α Reductase Inhibitors in Androgenetic Alopecia Treatment of Male Patients: A Network Meta-analysis.

IMPORTANCE: There are knowledge gaps regarding the relative efficacy of 3 commonly used drugs for androgenetic alopecia (AGA), namely, minoxidil and the two 5-α reductase inhibitors dutasteride and finasteride. OBJECTIVE: To examine the relative efficacy of any dose and administration route of minoxidil, dutasteride, and finasteride for the treatment of male AGA. DATA SOURCES: Systematic searches were performed in PubMed on March 5, 2021, without date restrictions. STUDY SELECTION: Eligible studies included those that investigated monotherapy with any dose and administration route of minoxidil, dutasteride, and finasteride. DATA EXTRACTION AND SYNTHESIS: Data on the mean (SD) difference and sample size were used for the bayesian network meta-analyses. League tables and surface under the cumulative ranking curve values were used to examine the relative efficacy of the interventions. MAIN OUTCOMES AND MEASURES: Study end points were change in total and terminal hair count after 24 and 48 weeks of therapy. The 4 end points were quantified in hairs per square centimeters. RESULTS: The PubMed search yielded 848 records; after the 2 stages of screening, 23 studies were eligible for quantitative analyses. Mean (SD) age of patients ranged from 22.8 (3.3) years to 41.8 (12.3) years. The greatest increase in total hair count at 24 weeks (ie, first end point) was with 0.5 mg/d of dutasteride, which was significantly more efficacious than 1 mg/d of finasteride (mean difference, 7.1 hairs/cm2; 95% CI, 5.1-9.3 hairs/cm2) and minoxidil (0.25 mg/d [mean difference, 23.7 hairs/cm2; 95% CI, 9.5-38.0 hairs/cm2], 5 mg/d [mean difference, 15.0 hairs/cm2; 95% CI, 3.9-26.1 hairs/cm2], and 2% solution [mean difference, 8.5 hairs/cm2; 95% CI, 4.8-12.3 hairs/cm2]). The greatest increase in terminal hair count at 24 weeks (ie, second end point) was with 5 mg/d of minoxidil, which was significantly more efficacious than the 0.25-mg/d dose (mean difference, 43.6 hairs/cm2; 95% CI, 29.7-57.7 hairs/cm2) and its topical forms (in 2% [mean difference, 29.3 hairs/cm2; 95% CI, 21.1-37.5 hairs/cm2] and 5% [mean difference, 29.8 hairs/cm2; 95% CI, 19.7-39.8 hairs/cm2]); 5 mg/d of minoxidil was significantly more efficacious than 1 mg/d of finasteride (mean difference, 10.4 hairs/cm2; 95% CI, 2.2-18.6 hairs/cm2). The greatest increase in total hair count at 48 weeks (ie, third end point) was with 5 mg/d of finasteride, which was significantly more efficacious than 2% topical minoxidil (mean difference, 20.7 hairs/cm2; 95% CI, 9.5-31.9 hairs/cm2). The greatest increase in terminal hair count at 48 weeks (ie, fourth end point) was with 1 mg/d of finasteride, which was significantly more effective than topical minoxidil (in 2% [mean difference, 32.1 hairs/cm2; 95% CI, 23.9-40.3 hairs/cm2] and 5% [mean difference, 26.2 hairs/cm2; 95% CI, 16.2-36.2 hairs/cm2]). CONCLUSIONS AND RELEVANCE: As efficacy data from head-to-head trials accumulate, there could be a better sense of the relative efficacy of the different doses of the 5-α reductase inhibitors and minoxidil. The findings of this meta-analysis contribute to the comparative effectiveness literature for AGA therapies with regard to the compared interventions.

Onychomycosis in children - review on treatment and management strategies.

BACKGROUND: Onychomycosis is an uncommon condition in children with increasing global prevalence. Health practitioners should confirm the diagnosis through mycology examination and examine family members of affected individuals for onychomycosis and tinea pedis. OBJECTIVE: To comprehensively summarize the treatment and management strategies for pediatric onychomycosis. METHODS: We performed a comprehensive literature search in the PubMed database to identify clinical studies on treatment for mycologically-confirmed dermatophyte onychomycosis in children <18 years. The exclusion criteria were combination therapy, case reports, reviews, systematic reviews and duplicate studies. RESULTS: Per-weight dosing regimens of systemic antifungal agents such as terbinafine, itraconazole, and fluconazole are found to be safe in children and are used off-label for the treatment of pediatric onychomycosis with high efficacy. Topical antifungal agents such as ciclopirox, efinaconazole, and tavaborole have established safety and efficacy in children. Children respond better than adults to topical therapy due to their thinner, faster growing nails. There is no data on the efficacy of medical devices for onychomycosis in children. CONCLUSION: Efinaconazole topical solution 10% and tavaborole topical solution 5% are FDA approved for the treatment of onychomycosis in children ≥6 years; ciclopirox topical solution 8% nail lacquer is approved in children ≥12 years.

Microneedling for Hair Loss.

BACKGROUND: Microneedling is a relatively novel therapeutic modality introduced in the 1990s where small, fine needles are used to create micro punctures in the skin. It is a minimally invasive procedure used for various dermatological conditions, including androgenetic alopecia (AGA). OBJECTIVE AND METHODS: We comprehensively summarize the literature regarding microneedling in dermatology. We performed linear multivariable regressions to synthesize evidence from the clinical trials that investigated the efficacy of microneedling for AGA. Studies eligible for quantitative analyses were assessed for evidence quality. RESULTS: The exact mechanism of microneedling action is yet to be determined, with theories that include the wound-healing cascade. Microneedling monotherapy significantly increased total hair count more than topical minoxidil 5% (ß = 12.29; p < 0.001). The combination treatment of microneedling with topical 5% minoxidil increased total hair count significantly compared to monotherapy with microneedling (ß = 7.63, p < 0.05). Increasing the overall treatment duration of microneedling and reducing the frequency of microneedling sessions may positively influence an increase in total hair count. CONCLUSION: There are limited studies that investigate microneedling as a monotherapy for hair loss since majority of the trials combine it with other therapies such as topical minoxidil or platelet-rich plasma. While preliminary results look promising, further investigation of microneedling as a monotherapy in larger, randomized controlled trials will help determine its safety and efficacy, and place in treating AGA.

JUBLIA (Efinaconazole 10% Solution) in the Treatment of Pediatric Onychomycosis.

Onychomycosis is a chronic fungal infection of the nails and is commonly observed in adults, especially the elderly, those who are diabetic, have poor peripheral circulation, and are immunocompromised; however, onychomycosis in children is being reported more frequently, especially in older children. There could also be a genetic predisposition to developing onychomycosis. Given that onychomycosis is uncommon in children, it is important to confirm the diagnosis mycologically. Treatment of onychomycosis includes oral or topical antifungal agents. In North America, the available oral antifungal agents are terbinafine, itraconazole, and fluconazole; however, none of these agents are approved by Food and Drug Administration (FDA) for children with onychomycosis. Terbinafine is, however, approved for tinea capitis in children aged 4 years and older. In general, these oral agents have been found to be safe and effective for pediatric onychomycosis. The available topical agents are efinaconazole solution 10%, tavaborole solution 5%, and ciclopirox nail lacquer topical solution 8%. The former two are approved by the FDA for the treatment of pediatric onychomycosis in children aged 6 years and older, while the third one is approved in children over the age of 12 years who have onychomycosis. In a phase-IV, multicenter, open label study, efinaconazole solution 10% was administered to children aged 6-16 years with culture positive, mild-to-severe distal and lateral subungual onychomycosis affecting ≥20% of at least one great toenail. Treatment was for 48 weeks, with follow-up at week 52. Efinaconazole solution 10% was found to be safe and well tolerated in this pediatric population. By week 52, the mycological cure was 65%, and the complete cure was 40%. The topical agents could be an important addition to the armamentarium of therapies available to treat pediatric onychomycosis safely and effectively.

One size does not fit all: the need for individualized treatment based on factors that may affect the therapeutic outcome of efinaconazole 10% solution for the treatment of toenail onychomycosis.

Successful management of onychomycosis is a challenge because cure rates with most antifungals are relatively low and recurrence rates are high. A drug-based approach by treating the nail alone may not suffice. There are several host-related factors (age, sex, body mass index [BMI], and patient's quality of life), disease-related factors (disease severity, duration, and the number of toenails affected), and comorbidities (tinea pedis and diabetes) that may affect treatment efficacy. Here, we review the post hoc analyses of the phase III trials of efinaconazole 10% solution that have investigated the impact of these factors on topical therapy for toenail onychomycosis. The significant clinical variables that may affect the efficacy of efinaconazole include sex, BMI, disease severity, disease duration, and tinea pedis. As older patients may have slower toenail growth and more severe, longstanding disease compared with younger patients, they may require longer treatment duration, beyond the 48-week standard regimen. Treatment compliance may need to be discussed for an improved health outcome. Therefore, these prognostic factors need to be carefully evaluated, which may aid in formulating individualized therapy to maximize treatment success.

Cure Rates of Control Interventions in Randomized Trials for Onychomycosis Treatments: A Systematic Review and Meta-Analysis.

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.

A Paradigm Shift in the Treatment and Management of Onychomycosis.

There is an increase in the incidence of onychomycosis, especially in at-risk populations. Onychomycosis is difficult to treat, as the efficacy of most antifungal agents is relatively low. Nondermatophyte molds (NDMs) and mixed infection (dermatophyte plus NDM) onychomycosis are contributing to growing antifungal resistance, as they are often underestimated and ignored due to incorrect diagnosis. There is a need for a paradigm shift in the management of onychomycosis to a patient-centered, holistic approach with an emphasis on laboratory diagnosis prior to initiating treatment, which enables the rational choice of the antifungal agent. Additionally, in the case of resistant infections, antifungal susceptibility testing is recommended. Strategies for effective management of onychomycosis include disinfection of fungal reservoirs in shoes and socks and prophylaxis posttreatment using topical antifungal agents. These measures may reduce the recurrence of onychomycosis and improve long-term clinical success.

More than Nail Deep: The Effect of Efinaconazole 10% Treatment on the Quality of Life in Patients with Onychomycosis: A post hoc Study.

INTRODUCTION: Onychomycosis is a common, difficult-to-treat fungal nail infection. Clinical signs include nail discoloration and thickening, which patients often find embarrassing, causing a negative impact on their quality of life (QOL). METHODS: In this post hoc study, we analyze the effect of efinaconazole 10% solution on a patient's QOL using patient-reported scores from the OnyCOE-t™ questionnaire (appearance, stigma, physical problems, symptom frequency, symptom bothersomeness, treatment satisfaction, and overall problem). Higher scores corresponded to better functioning, thus higher QOL. RESULTS: Efinaconazole 10% treatment and clinical efficacy were positively correlated with improved QOL in all domains for all groups, except with symptom bothersomeness (how much the onychomycosis symptoms worried or concerned the patient) for female patients <40 years. While still showing improvement in most domains during efficacious treatment, female and younger patients reported lower QOL scores than their male and older counterparts, despite having better clinical outcomes at follow-ups. DISCUSSION: Female and younger patients appear to be more emotionally bothered by their symptoms, regardless of treatment success or improvement of their nail's appearance, suggesting that onychomycosis is more than nail deep and has a greater psychological effect on these patients. Therefore, younger female patients may require more assurance and mental support.

The increasing problem of treatment-resistant fungal infections: a call for antifungal stewardship programs.

Antimicrobial stewardship (AMS) programs have been widely recognized among the public health community. These programs focus majorly on bacterial infections, efficient antibiotic use, and measures to curb increasing antibacterial resistance. AMS programs are successfully established around the globe; however, very few include antifungal stewardship (AFS). The increasing incidence of superficial and invasive fungal infections, combined with delayed or inaccurate diagnosis, has contributed to the overprescribing and overuse of antifungal agents. Such increased exposure to antifungal agents may be a reason for the emergence of increasing antifungal resistance among fungal pathogens. With mounting reports of treatment failures and resistant infections, the evidence to support the need for AFS programs is increasing. AFS is an emerging branch of AMS programs that requires global attention and recognition.

Rapid Real-Time Antimicrobial Susceptibility Testing with Electrical Sensing on Plastic Microchips with Printed Electrodes.

Rapid antimicrobial susceptibility testing is important for efficient and timely therapeutic decision making. Due to globally spread bacterial resistance, the efficacy of antibiotics is increasingly being impeded. Conventional antibiotic tests rely on bacterial culture, which is time-consuming and can lead to potentially inappropriate antibiotic prescription and up-front broad range of antibiotic use. There is an urgent need to develop point-of-care platform technologies to rapidly detect pathogens, identify the right antibiotics, and monitor mutations to help adjust therapy. Here, we report a biosensor for rapid (<90 min), real time, and label-free bacteria isolation from whole blood and antibiotic susceptibility testing. Target bacteria are captured on flexible plastic-based microchips with printed electrodes using antibodies (30 min), and its electrical response is monitored in the presence and absence of antibiotics over an hour of incubation time. We evaluated the microchip with Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) as clinical models with ampicillin, ciprofloxacin, erythromycin, daptomycin, gentamicin, and methicillin antibiotics. The results are compared with the current standard methods, i.e. bacteria viability and conventional antibiogram assays. The technology presented here has the potential to provide precise and rapid bacteria screening and guidance in clinical therapies by identifying the correct antibiotics for pathogens.

An automated smartphone-based diagnostic assay for point-of-care semen analysis.

Male infertility affects up to 12% of the world's male population and is linked to various environmental and medical conditions. Manual microscope-based testing and computer-assisted semen analysis (CASA) are the current standard methods to diagnose male infertility; however, these methods are labor-intensive, expensive, and laboratory-based. Cultural and socially dominated stigma against male infertility testing hinders a large number of men from getting tested for infertility, especially in resource-limited African countries. We describe the development and clinical testing of an automated smartphone-based semen analyzer designed for quantitative measurement of sperm concentration and motility for point-of-care male infertility screening. Using a total of 350 clinical semen specimens at a fertility clinic, we have shown that our assay can analyze an unwashed, unprocessed liquefied semen sample with <5-s mean processing time and provide the user a semen quality evaluation based on the World Health Organization (WHO) guidelines with ~98% accuracy. The work suggests that the integration of microfluidics, optical sensing accessories, and advances in consumer electronics, particularly smartphone capabilities, can make remote semen quality testing accessible to people in both developed and developing countries who have access to smartphones.