Treatments for Onychomycosis: A Bibliometric Analysis.

Introduction: Oral antifungals were the earliest treatments to receive approval for the management of onychomycosis and have a long-standing record to support their efficacy. Topical antifungals and device-based treatments have been explored and some implemented in more recent years as alternatives to traditional oral antifungals. The present bibliometric analysis summarizes trends in publication frequency for onychomycosis treatment modalities over time and characterizes their body of literature in terms of types of studies available and relative level of evidence. Methods: A comprehensive literature search was performed using Web of Science and SCOPUS databases. Results: Covering all publications from 1970 to present day, our search identified oral therapeutics n = 295 articles (n = 63 randomized control trials [RCTs]), topical therapeutics n = 358 articles (n = 72 RCTs), and device-based treatments n = 158 articles (n = 37 RCTs). Spikes in research activity surround FDA approval of therapeutics for each treatment modality. Research activity within the last decade has focused on topical and device-based treatments. Evidence for efficacy of device-based treatments is lacking from relatively few high-quality RCTs. Conclusion: With growing concern for non-dermatophyte mold onychomycosis and terbinafine resistance, researchers should validate the efficacy and safety of device-based treatments with high-quality studies.

OpzeluraTM (Ruxolitinib) Cream 1.5.

Ruxolitinib cream 1.5% was first approved by the US Food and Drug Administration (FDA) in 2011. Opzelura™ cream was introduced by Incyte Dermatology in 2021 for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients aged ≥12 years, whose clinical manifestations are not controlled with prescribed topical therapies, such as topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase-4 ( PDE4) inhibitors, or when such therapies are not advisable. Ruxolitinib is a Janus kinase (JAK) inhibitor that addresses inflammation in AD. It selectively inhibits JAK1 and JAK2, blocking JAK and activating signal transducer and activator of transcription (STAT), thereby interrupting the cytokine pathways responsible for cutaneous inflammation. The targeted downstream cytokines include Interleukin- 4 (IL-4), IL-13, IL-31, and cytokine thymic stromal lymphopoietin (TSLP), which play pivotal roles in the itching and inflammation experienced by AD patients. Ruxolitinib cream is directly applied as a thin layer over AD lesions twice daily up to 20% body surface area (BSA) using no more than 60 g per week. It can be used for up to 8 weeks on delicate or thin skin surfaces.

DAXXIFYTM (DaxibotulinumtoxinA-Lanm) for Injection, for Intramuscular Use.

DAXXIFYTM (daxibotulinumtoxinA-lanm) for intramuscular injection was recently approved for temporary improvement in the appearance of the moderate to severe glabellar lines (GLs) associated with corrugator and/or procerus muscle activity in adult patients. DaxibotulinumtoxinA for Injection (DAXI) includes a purified 150-kDA botulinum toxin Type A (BoNTA) formulated with a novel peptide excipient that is positively charged and helps to bind the neurotoxin to negatively charged neuronal membrane for a longer duration. The effectiveness of DAXI was evaluated in two phase 3 trials, SAKURA 1 and SAKURA 2, using a randomized, double-blind, placebo-controlled design. The primary endpoint (treatment success) was a composite clinical outcome (investigator and subjects) of ≥2-point improvement in severity of GLs at week 4. In SAKURA 1, the treatment success was 74% (148/201) in subjects treated with DAXI and 0% in subjects treated with placebo. In SAKURA 2, the treatment success was 74% (152/205) in subjects treated with DAXI and 0% in subjects treated with placebo. An open-label study, SAKURA 3, included 2,691 participants, who underwent three consecutive treatment cycles. These individuals were recruited from either SAKURA 1 or SAKURA 2 trials, or were new to the study and received DAXI. Treatment success proportions were 73.2%, 77.7%, and 79.6% across the three consecutive treatment cycles. The recommended dose is 40 units for the Glabellar-complex divided in traditional five intramuscular injections at five injection sites (medial and lateral corrugator bilaterally and one injection in the procerus muscle).

Pediatric dermatophyte onychomycosis: a review.

Recent studies have reported an increase in pediatric onychomycosis prevalence worldwide, suggesting that this population may be increasingly affected by the infection. A summary of the epidemiological impact, antifungal treatment options, special considerations for at-risk subpopulations, and methods to prevent infection and recurrence are discussed. A systematic review of available epidemiological studies found the worldwide prevalence of culture-confirmed pediatric toenail onychomycosis to be 0.33%, with no significant increases in prevalence over time. A systematic review of studies investigating the efficacy of various antifungals in treating pediatric onychomycosis found high cure rates and low frequency of adverse events with systemic itraconazole and terbinafine; however, the studies are few, dated, and lack impact because of small sample sizes. Comparatively, clinical trials implementing FDA-approved topical antifungal treatments report slightly reduced cure rates with larger sample sizes. Patients with immunity-altering conditions, such as Down's syndrome, or those immunosuppressed because of chemotherapy or HIV/AIDS are at a greater risk of onychomycosis infection and require special consideration with treatment. Proper sanitization and hygiene practices are necessary to reduce the risk of acquiring infection. Early diagnosis and treatment of onychomycosis in children, as well as any affected close contacts, are crucial in reducing the impact of the disease.

Extended Use of Topical Efinaconazole Remains Safe and Can Provide Continuing Benefits for Dermatophyte Toenail Onychomycosis.

INTRODUCTION: Efinaconazole 10% topical solution labeling for onychomycosis describes phase III trials of 12 months of treatment; the slow growth of onychomycotic nails suggests a longer treatment period may increase efficacy. We present here the first evaluation of extended use of efinaconazole 10% topical solution for up to 24 months. MATERIALS AND METHODS: Enrolled patients (n = 101) had one target great toenail with mild to moderate distal lateral subungual onychomycosis and applied efinaconazole 10% topical solution to all affected toenails once daily for 18 months (EFN18) or 24 months (EFN24). Efficacy and safety were evaluated at each visit by visual review and mycology sampling. RESULTS: Regarding the target toenail for patients treated for 24 months (EFN24), mycological cure (negative microscopy and culture) was 66.0% at Month 12, increasing to 71.7% at Month 24; effective cure (mycological cure and ≤10% affected nail) was 13.2% at Month 12, rising to 22.6% at Month 24. Mild to moderate application site reactions (symptoms of erythema/scaling) were the only efinaconazole-related reactions, in eight patients (7.9%). No systemic efinaconazole events or drug interactions were found. Patients aged 70 years or more had similar efficacy to younger patients at all time periods and did not show any increased treatment risks. Thinner nails exhibited better clearance versus thicker nails. A higher proportion of patients with Trichophyton mentagrophytes complex infection experienced application site reactions (35.7%), and a higher effective cure was found at Month 24 versus T. rubrum patients. CONCLUSION: There is a trend of increasing mycological cure and effective cure beyond Month 12 to Month 24, without an increased safety risk. The enrolled population in this trial was significantly older than in the phase III trials, with a greater degree of onychomycosis severity; however, increased age did not appear to reduce the chance of efficacy to Month 24 in this study. Our data suggest that lack of ability to clear nail dystrophy remains a significant problem for patients, rather than any lack of efinaconazole action over long-term treatment periods.

Epidemiology of Onychomycosis in the United States Characterized Using Molecular Methods, 2015-2024.

Onychomycosis is a recalcitrant fungal infection of the nail unit that can lead to secondary infections and foot complications. Accurate pathogen identification by confirmatory testing is recommended to improve treatment outcomes. In this study, we reviewed the records of 710,541 patients whose nail specimens were sent to a single molecular diagnostic laboratory between 2015 and 2024. PCR testing revealed a more comprehensive spectrum of pathogens than previously reported, which was corroborated by the demonstration of fungal invasion on histopathology. Consistent with our current understanding, the T. rubrum complex (54.3%) are among the most common pathogens; however, a significant portion of mycology-confirmed diagnoses were caused by the T. mentagrophytes complex (6.5%), Aspergillus (7.0%) and Fusarium (4.5%). Females were significantly more likely to be infected with non-dermatophytes molds (NDMs; OR: 2.0), including Aspergillus (OR: 3.3) and Fusarium (OR: 2.0), and yeasts (OR: 1.5), including Candida albicans (OR: 2.0) and C. parapsilosis (OR 1.6), than males. The T. mentagrophytes complex became more prevalent with age, and conversely the T. rubrum complex became less prevalent with age. Patients aged ≥65 years also demonstrated a higher likelihood of contracting onychomycosis caused by NDMs (OR: 1.6), including Aspergillus (OR: 2.2), Acremonium (OR: 3.5), Scopulariopsis (OR: 2.9), Neoscytalidium (OR: 3.8), and yeasts (OR: 1.8), including C. albicans (OR: 1.9) and C. parapsilosis (OR: 1.7), than young adults. NDMs (e.g., Aspergillus and Fusarium) and yeasts were, overall, more likely to cause superficial onychomycosis and less likely to cause dystrophic onychomycosis than dermatophytes. With regards to subungual onychomycosis, Aspergillus, Scopulariopsis and Neoscytalidium had a similar likelihood as dermatophytes. The advent of molecular diagnostics enabling a timely and accurate pathogen identification can better inform healthcare providers of appropriate treatment selections and develop evidence-based recommendations.

Low-Dose Oral Minoxidil and Associated Adverse Events: Analyses of the FDA Adverse Event Reporting System (FAERS) With a Focus on Pericardial Effusions.

BACKGROUND: Low-dose oral minoxidil (LDOM) is used to treat hair loss, but the literature on its safety profile is relatively sparse. AIMS: Using the FDA Adverse Event Reporting System (FAERS) database, we determined signals for adverse events (AEs) with LDOM use. METHODS: Four sets of case/noncase study disproportionality analyses were conducted to determine reporting odds ratio (ROR) for 10 AEs including pericardial effusion (PE). The oral minoxidil dose ranges were: (i) ≤1.25 mg (i.e., 0-1.25 mg), (ii) ≤2.5 mg (i.e., 0-2.5 mg), (iii) ≤5 mg (i.e., 0-5 mg), and (iv) ≤10 mg (i.e., 0-10 mg). RESULTS: For ≤1.25 mg, we detected a signal for PE (ROR = 16.41, 95% CI: 2.29, 117.37, p < 0.05). For ≤2.5 mg, the analyses detected a signal for PE (ROR = 13.30, 95% CI: 5.96, 29.68, p < 0.05); the ROR in the absence of cardiac impairment was 5.34 (95% CI: 1.33, 21.37, p < 0.05); in the presence of cardiac impairment, the ROR was 49.42 (95% CI: 18.27, 133.66, p < 0.05). A signal for PE was also detected at ≤5 and ≤10 mg. For PE, there was a significant (p < 0.05) association with a patient outcome of "life threatening" only at the ≤10 mg dose range. CONCLUSIONS: Our study, the first FAERS-based signal detection study for LDOM, found significant associations between LDOM use and several AEs. In the absence of causal evidence, these correlations warrant more attention regarding safe use of LDOM. Until more safety data are available, we recommend using LDOM at the lowest effective dose (≤5 mg/day).

Antifungal resistance in dermatophytes - review of the epidemiology, diagnostic challenges and treatment strategies for managing Trichophyton indotineae infections.

INTRODUCTION: There is an increasing number of reports of Trichophyton indotineae infections. This species is usually poorly responsive to terbinafine. AREAS COVERED: A literature search was conducted in May 2024. T.indotineae infections detected outside the Indian subcontinent are generally associated with international travel. Reports of local spread are mounting.As a newly identified dermatophyte species closely related to the T. mentagrophytes complex with limited genetic and phenotypic differences, there is an unmet need to develop molecular diagnosis for T. indotineae. Terbinafine has become less effective as a first-line agent attributed to mutations in the squalene epoxidase gene (Leu393Phe, Phe397Leu). Alternative therapies include itraconazole for a longer time-period or a higher dose (200 mg/day or higher). Generally, fluconazole and griseofulvin are not effective. In some cases, especially when the area of involvement is relatively small, topical non-allylamine antifungals may be an option either as monotherapy or in combination with oral therapy. In instances when the patient relapses after apparent clinical cure then itraconazole may be considered. Good antifungal stewardship should be considered at all times. EXPERT OPINION: When both terbinafine and itraconazole are ineffective, options include off-label triazoles (voriconazole and posaconazole). We present four patients responding to these newer triazoles.

Ringworm (dermatophytosis, tinea) is a fungal infection of the skin, hair and nails that is commonly seen by primary and secondary healthcare providers. An estimated 20­25% of the global population is affected by this condition. In Europe and the United States, tineas are often treated empirically using over-the-counter medications, which can increase the risk of resistance development.While antifungal resistance is not a new problem, this topic has garnered the attention of physicians and researchers in recent years due to an outbreak from South Asia caused by a new pathogen known as Trichophyton indotineae. In this review, we summarize the global prevalence, diagnosis methods, antifungal resistance profile and treatment options for T. indotineae. Currently, most cases outside of South Asia are linked to international travel, there is evidence suggesting local person-to-person transmission and transmission via animal contact. One hurdle to surveilling the spread of this pathogen is the requirement of complex molecular diagnosis, tackling this challenge will require the development of newer assays.Terbinafine, a widely available antifungal drug, is becoming less effective owing to resistance mutations of the squalene epoxidase gene. Itraconazole has shown effectiveness, especially with a higher dose and a longer treatment duration. There is a significant risk of T. indotineae infections becoming chronic with episodes of relapse. When both terbinafine and itraconazole fail, newer agents such as posaconazole and voriconazole can be considered. Combination therapy using oral and topical medications should also be considered.

Systemic absorption and safety of topical terbinafine hydrochloride 10% solution (MOB015B): a phase 1 maximal usage trial in patients with moderate-to-severe onychomycosis.

Topical antifungals may be considered to treat onychomycosis with minimal risk of systemic side effects. In this study, we assess the safety, tolerability, systemic exposure, and pharmacokinetic characteristics of topical terbinafine hydrochloride 10% solution (MOB015B) in adults with moderate-to-severe onychomycosis. Clinically and mycologically confirmed patients with toenail onychomycosis (N = 20) were enrolled in this single-center, open-label study . Each patient had ≥50% involvement of both great toenails and at least four additional toenails affected. MOB015B was applied once daily to all toenails for 28 days. Blood was drawn on days 1, 14, and 28. Plasma concentrations of MOB015B after the first dose were quantifiable in all subjects by 24 h. Steady-state levels in plasma were reached by day 28. The mean systemic exposure on day 28 of 0.72 ng/mL for maximum plasma concentration (Cmax) was approximately 2,000 times lower than the mean plasma level of 1.39 µg/mL seen after oral administration of 250 mg terbinafine for 28 days. Adverse events (five patients), such as headache (n = 3), seasonal allergy (n = 1), and neck pain (n = 1), were considered unrelated to MOB015B; no application site reactions or study discontinuations due to an adverse event were observed. MOB015B applied to all affected toenails under maximal usage conditions for 28 days demonstrated very low levels of terbinafine in plasma (Cmax <1 ng/mL after 28 days), consistent with a favorable safety and tolerability profile. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT03244280.

Libtayo® (Cemiplimab-rwlc) Injection for Intravenous Use.

Libtayo® (cemiplimab-rwlc) injection for intravenous use was recently approved by the US Food and Drug Administration (FDA) for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC), both being the advanced stages of BCC. In the past, it was approved by the FDA for the treatment of metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC), both being the advanced stages of CSCC. Cemiplimab is a monoclonal antibody that works by blocking the programmed death-1 pathway. In two open-label, single-arm, phase 2 studies, cemiplimab was investigated for the treatment of advanced stages of BCC (study 1620, NCT03132636) and advanced stages of CSCC (study 1540, NCT02760498). The primary endpoint was objec-tive response rate (ORR) per independent central review. In the study 1620, both mBCC and laBCC received cemiplimab 350 mg every 3 weeks. ORR was 21% (6/28) and 31% (26/84) in the mBCC and laBCC groups, respectively. In the study 1520, mCSCC was divided into two groups: one receiving cemiplimab 350 mg every 3 weeks (Q3W) and another receiving 3-mg/kg cemiplimab every 2 weeks (Q2W); the third group, laCSCC, received cemiplimab 3 mg/kg every 2 weeks. ORR was 41% (23/56) in the Q3W group, 49% (29/59) in the Q2W group, and 44% (34/78) in the laCSCC group. An acceptable safety profile and antitumor activity was discovered in patients treated with cemiplimab. The recommended dosage for cemiplimab to treat advanced stages of BCC and CSCC is 350 mg every 3 weeks administered intravenously over 30 min.

The Comparative Effects of Monotherapy with Topical Minoxidil, Oral Finasteride, and Topical Finasteride in Postmenopausal Women with Pattern Hair Loss: A Retrospective Cohort Study.

Introduction: Oral finasteride and topical minoxidil are long-standing androgenetic alopecia (AGA) treatments; topical finasteride is a more recent medicine. Few studies have compared their therapeutic effects in postmenopausal women. We compared the therapeutic impact of topical finasteride (1-4 sprays of 0.25% topical finasteride solution daily for 12 months), oral finasteride (2.5 mg oral finasteride once daily for 12 months), and topical minoxidil (1 mL of topical minoxidil 5% twice daily for 12 months) in postmenopausal women with AGA. Methods: We conducted Bayesian network meta-analyses of individual patient-level data insofar as four clinically relevant endpoints, namely, 12-month change in (1) total hair density, (2) hair diameter, (3) clinical photographs, and (4) patients' opinion of efficacy. Data were obtained through medical charts. Regimens' surface under the cumulative ranking distribution (SUCRA) values and relative effects - as per odds ratios - were computed. Results: As per SUCRA, the most and least effective regimens - across the four outcomes - were oral finasteride, and topical finasteride, respectively; however, no significant statistical differences were found (i.e., p > 0.05). Conclusion: Oral finasteride is ranked more effective than the topical forms of minoxidil and finasteride; however, more studies are needed to confirm this result.

An update on tinea capitis in children.

Tinea capitis presents a significant public health care challenge due to its contagious nature, and potential long-term consequences if unrecognized and untreated. This review explores the prevalence, risk factors, diagnostic methods, prevention strategies, impact on quality of life, and treatment options for pediatric tinea capitis. Epidemiological analysis spanning from 1990 to 1993 and 2020 to 2023 reveals prevalence patterns of pediatric tinea capitis influenced by geographic, demographic, and environmental factors. Notably, Trichophyton species is most prevalent in North America; however, Microsporum species remain the primary causative agent globally, with regional variations. Risk factors include close contact and environmental conditions, emphasizing the importance of preventive measures. Accurate diagnosis relies on clinical evaluation, microscopic examination, and fungal culture. Various treatment modalities including systemic antifungals show efficacy, with terbinafine demonstrating superior mycological cure rates particularly for Trichophyton species. Recurrent infections and the potential development of resistance can pose challenges. Therefore, confirming the diagnosis, appropriately educating the patient/caregiver, accurate drug and dose utilization, and compliance are important components of clinical cure. Untreated or poorly treated tinea capitis can lead to chronic infection, social stigma, and psychological distress in affected children. Prevention strategies focus on early detection and healthy lifestyle habits. Collaborative efforts between healthcare providers and public health agencies are important in treating pediatric tinea capitis and improving patient outcomes. Education and awareness initiatives play a vital role in prevention and community-level intervention to minimize spread of infection. Future research should explore diagnostic advances, novel treatments, and resistance mechanisms in order to mitigate the disease burden effectively.

Spevigo® (Spesolimab-Sbzo) Injection for the Treatment of Generalized Pustular Psoriasis.

Spevigo® (spesolimab-sbzo) injection was recently approved for the treatment of generalized pustular psoriasis (GPP) in adults aged 18- 75 years. Spesolimab, a monoclonal antibody, binds to the interleukin-36 (IL-36) receptor and prevents its activation by IL-36 cytokines, leading to reduced inflammation, skin lesions, and flares. In a randomized placebo-controlled, phase 2 study (Effisayil-1, NCT03782792), 53 patients were randomized to spesolimab (n = 35) and placebo (n = 18) to evaluate the effect of a one-time 900-mg dose of spesolimab versus placebo against GPP flares. The primary endpoint was Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 (no visible pustules) and the key secondary endpoint was the GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1. The primary endpoint was achieved by 54% (19/35) of patients in the spesolimab group and 6% (1/18) of patients in the placebo group. The key secondary endpoint was achieved by 43% (15/35) of patients in the spesolimab group and 11% (2/18) of patients in the placebo group. In the first week, adverse events (mild to severe) were reported in 66% (22/35) of patients in the spesolimab group and 56% (10/18) in the placebo group.

OtezlaTM (Apremilast 30-Mg Tablets).

OtezlaTM was first approved on March 21, 2014 for the treatment of psoriatic arthritis, on September 23, 2014 for moderate to severe plaque psoriasis and on July 19, 2019 for the treatment of oral ulcers associated with Behcet's disease (BD). Apremilast is an inhibitor of phosphodi-esterase-4, an enzyme involved in the pathogenesis of several dermatologic conditions. This review explores the potential utility of apremilast in the treatment of other unapproved dermatologic indications.

Diabetic Foot and Fungal Infections: Etiology and Management from a Dermatologic Perspective.

Diabetes Mellitus (DM) is a significant global concern. Many diabetic patients will experience complications due to angiopathy, neuropathy, and immune dysfunction, namely diabetic foot ulcers (DFU) and diabetic foot infections (DFI), which can result in lower limb amputation and potentially death. The prevalence of common superficial fungal infections, such as tinea pedis and onychomycosis, can directly increase a diabetic patient's risk of developing both DFU and DFI. In this review article, we discuss the etiology of diabetic foot complications as well as considerations for both screening and management. We also discuss the role of the dermatologist within a multidisciplinary care team in prescribing and managing treatments for tinea pedis and onychomycosis infections within this patient population. We believe that reducing the burden of these fungal infections in the context of the diabetic foot will help reduce DFU and DFI complications and their associated morbidity and mortality.

Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States.

BACKGROUND: There is a concerning rise in antifungal-resistant dermatophytosis globally, with resistance to terbinafine conferred by point mutations in the squalene epoxidase (SQLE) gene. OBJECTIVES: Report changes in the prevalence and profile of SQLE mutations in onychomycosis patients in the United States. METHODS: A longitudinal cohort study of toenail samples was collected from suspected onychomycosis patients over an 18-month period from 2022 to 2023. Samples were submitted from across the United States and subjected to multiplex real-time polymerase chain reactions for dermatophyte detection, with further screening of SQLE mutations at four known hotspots (393Leu, 397Phe, 415Phe and 440His). RESULTS: A total of 62,056 samples were submitted (mean age: 57.5 years; female: 60.4%). Dermatophytes were detected in 38.5% of samples, primarily Trichophyton rubrum complex (83.6%) and T. mentagrophytes complex (10.7%). A survey of SQLE mutations was carried out in 22,610 dermatophyte samples; there was a significant increase in the prevalence of SQLE mutations between the first quarter of 2022 and the second quarter of 2023 (29.0 to 61.9 per 1000 persons). The Phe397Leu substitution was the predominant mutation; Phe415Ser and His440Tyr have also emerged which were previously reported as minor mutations in skin samples. The temporal change in mutation rates can be primarily attributed to the Phe415Ser substitution. Samples from elderly patients (>70 years) are more likely to be infected with the T. mentagrophytes complex including strains harbouring the Phe415Ser substitution. CONCLUSION: The prevalence of SQLE mutations among onychomycosis patients with Trichophyton infections may be underestimated. Older individuals may have a higher risk.

Comparison of therapeutic agents' short-term effects on facial and scalp actinic keratosis: A network meta-analysis.

BACKGROUND: Care for actinic keratosis (AK) can be improved with more knowledge on the relative of effect of indicated therapies. OBJECTIVES: Using network meta-analyses, we quantitatively determined the comparative "short-term" effects of interventions in adults with facial and scalp AK. METHODS: On February 28, 2023, evidence from the peer-reviewed literature was systematically obtained from OVID, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. We analyzed data from studies published in English, of a trial design, and investigating the effect of an actinic keratosis monotherapy. Patient complete clearance, patient partial clearance or lesion-specific clearance across adults were analyzed at 8-12 weeks after therapy. Patient complete clearance pertained to proportion of participants who experienced complete clearance of actinic keratosis lesions; patient partial clearance corresponded to percentage of subjects who achieved at least 75% clearance of actinic keratosis lesions; lesion-specific clearance represented the percentage of all lesions that were cleared. In the main (i.e., base) analyses, nodes were analyzed only at the level of the agent. RESULTS: Data from a total of 84 studies were used-across which 22 active agents were identified. Estimates of interventions' surface under the cumulative ranking curve rankings and (pairwise) relative effects were estimated. Across the three outcomes, fluorouracil 5% was ranked the most effective. CONCLUSIONS: Our work is the first to provide information on covariate-adjusted relative effects of actinic keratosis therapies- including the more recently reported treatments-for the face and scalp; this knowledge may help physicians and patients make more informed decisions.

A bibliometric analysis of alternative drug therapy options in the treatment of androgenetic alopecia.

BACKGROUND: Oral finasteride and topical minoxidil formulations are the only FDA-approved drug therapies for androgenetic alopecia (AGA). Research into dutasteride, topical finasteride, and nontopical minoxidil (low-dose oral and sublingual) formulations in the treatment of AGA has spiked within recent years. Early findings show that these alternative drug therapies may have similar to improved efficacy and safety profiles relative to the conventional treatment options. AIMS: Conducting a bibliometric analysis, compare trends in publications on these alternative drug therapies, identify key contributors, evaluate major findings from top-cited articles, and elucidate gaps in evidence. METHODS: A search was conducted on the Web of Science database for publications on the use of alternative drug therapies in the treatment of AGA. A total of 95 publications, published between January 2003-March 2024, and their citation metadata were included in the analysis. RESULTS: Dutasteride showed the greatest (n = 37) and longest (20+ years) history of publications, as well as the highest cumulative citations (n = 914); however, nontopical minoxidil showed a burst in research activity within the last 5 years (n = 33 publications since 2019). A relatively low number of randomized control trials (n = 3) for nontopical minoxidil suggests a need for higher-quality evidence. CONCLUSIONS: Our analysis reveals major trends, contributors, and gaps in evidence for alternative drug therapies for AGA, which can help inform researchers on their future projects in this growing field of study. There is enthusiasm for exploring off-label formulations: nontopical forms of minoxidil (oral and sublingual), topical finasteride, and mesotherapy.

Safety and efficacy of new generation azole antifungals in the management of recalcitrant superficial fungal infections and onychomycosis.

INTRODUCTION: Terbinafine is considered the gold standard for treating skin fungal infections and onychomycosis. However, recent reports suggest that dermatophytes are developing resistance to terbinafine and the other traditional antifungal agents, itraconazole and fluconazole. When there is resistance to terbinafine, itraconazole or fluconazole, or when these agents cannot used, for example, due to potential drug interactions with the patient's current medications, clinicians may need to consider off-label use of new generation azoles, such as voriconazole, posaconazole, fosravuconazole, or oteseconazole. It is essential to emphasize that we do not advocate the use of newer generation azoles unless traditional agents such as terbinafine, itraconazole, or fluconazole have been thoroughly evaluated as first-line therapies. AREAS COVERED: This article reviews the clinical evidence, safety, dosage regimens, pharmacokinetics, and management algorithm of new-generation azole antifungals. EXPERT OPINION: Antifungal stewardship should be the top priority when prescribing new-generation azoles. First-line antifungal therapy is terbinafine and itraconazole. Fluconazole is a consideration but is generally less effective and its use may be off-label in many countries. For difficult-to-treat skin fungal infections and onychomycosis, that have failed terbinafine, itraconazole and fluconazole, we propose consideration of off-label voriconazole or posaconazole.

The impact of monotherapies for male androgenetic alopecia: A network meta-analysis study.

BACKGROUND: The evidence base pertaining to the efficacy of monotherapies for androgenetic alopecia (AGA), the most common form of hair loss, is ever expanding-and this warrants a formal comparison therapies' effect on a frequent basis. AIMS: The objective of the current study was to determine the comparative effect of relevant monotherapies for male AGA. PATIENTS/METHODS: Our aim was achieved by conducting Bayesian network meta-analysis (NMA), under a random effects model, for two outcomes: 6-month change in (1) total and (2) terminal hair density in adult (i.e., aged 18 years and above) men with AGA; these analyses were preceded by a systematic search of the peer-reviewed literature for suitable data. Interventions' surface under the cumulative ranking curve (SUCRA) and pairwise relative effects (quantified as mean differences) were estimated through the NMAs. RESULTS: We determined the comparative effect of 20 active comparators and a control (i.e., placebo/vehicle). "Dutasteride 0.5 mg once daily for 24 weeks" was ranked the most effective in terms of 6-month change in (1) total hair density (SUCRA = 87%) and terminal hair density (SUCRA = 98%). Our results showed that interventions' effectiveness can be dose dependent. CONCLUSIONS: Our updated analyses of the up-to-date evidence regarding monotherapies for male AGA showed that the oral form of 5-alpha reductase inhibitors are more effective than oral minoxidil and other newer agents like Botox, microneedling, and photobiomodulation. Our findings can better inform clinical decision making and design of future research studies.