Global prevalence of onychomycosis in general and special populations: An updated perspective.

BACKGROUND: Onychomycosis is a chronic nail disorder commonly seen by healthcare providers; toenail involvement in particular presents a treatment challenge. OBJECTIVE: To provide an updated estimate on the prevalence of toenail onychomycosis. METHODS: We conducted a literature search using PubMed, Embase and Web of Science. Studies reporting mycology-confirmed diagnoses were included and stratified into (a) populations-based studies, and studies that included (b) clinically un-suspected and (c) clinically suspected patients. RESULTS: A total of 108 studies were included. Based on studies that examined clinically un-suspected patients (i.e., with or without clinical features suggestive of onychomycosis), the pooled prevalence rate of toenail onychomycosis caused by dermatophytes was 4% (95% CI: 3-5) among the general population; special populations with a heightened risk include knee osteoarthritis patients (RR: 14.6 [95% CI: 13.0-16.5]), chronic venous disease patients (RR: 5.6 [95% CI: 3.7-8.1]), renal transplant patients (RR: 4.7 [95% CI: 3.3-6.5]), geriatric patients (RR: 4.7 [95% CI: 4.4-4.9]), HIV-positive patients (RR: 3.7 [95% CI: 2.9-4.7]), lupus erythematosus patients (RR: 3.1 [95% CI: 1.2-6.3]), diabetic patients (RR: 2.8 [95% CI: 2.4-3.3]) and hemodialysis patients (RR: 2.8 [95% CI: 1.9-4.0]). The prevalence of onychomycosis in clinically suspected patients was significantly higher likely due to sampling bias. A high degree of variability was found in a limited number of population-based studies indicating that certain pockets of the population may be more predisposed to onychomycosis. The diagnosis of non-dermatophyte mould onychomycosis requires repeat sampling to rule out contaminants or commensal organisms; a significant difference was found between studies that performed single sampling versus repeat sampling. The advent of PCR diagnosis results in improved detection rates for dermatophytes compared to culture. CONCLUSION: Onychomycosis is an underrecognized healthcare burden. Further population-based studies using standardized PCR methods are warranted.

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.

Onychomycosis in the US Pediatric Population-An Emphasis on Fusarium Onychomycosis.

BACKGROUND: Onychomycosis is a common nail disease that is often difficult to treat with a high risk of recurrence. OBJECTIVE: To update our current understanding of the etiologic profile in pediatric patients with onychomycosis utilizing molecular diagnosis by polymerase chain reaction (PCR) combined with histopathologic examination. METHODS: Records of 19,770 unique pediatric patients were retrieved from a single diagnostic laboratory in the United States spanning over a 9-year period (March 2015 to April 2024). This cohort represents patients clinically suspected of onychomycosis seen by dermatologists and podiatrists. Dermatophytes, nondermatophyte molds (NDMs), and yeasts were identified by multiplex real-time PCR corroborated by the demonstration of fungal invasion on histopathology. RESULTS: An average of 37.0% of all patients sampled were mycology-confirmed to have onychomycosis. Most patients were between ages 11 and 16 years, and the rate of mycologically confirmed onychomycosis was significantly higher among the 6- to 8-year (47.2%) and 9- to 11-year (42.7%) age groups compared to the 0- to 5-year (33.1%), 12- to 14-year (33.2%), and 15- to 17-year (36.7%) age groups. The majority of infections were caused dermatophytes (74.7%) followed by NDMs (17.4%). The Trichophyton rubrum complex represents the dominant pathogen with higher detection rates in the 6- to 11-year-olds. Fusarium was the most commonly isolated NDM with an increasing prevalence with age. CONCLUSIONS: Elementary school-aged children have a higher risk of contracting onychomycosis which may be attributed to the onset of hyperhidrosis at puberty, use of occlusive footwear, nail unit trauma, and walking barefoot. Fusarium onychomycosis may be more prevalent than expected, and this may merit consideration of management strategies.

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.

Mapping the Global Spread of T. indotineae: An Update on Antifungal Resistance, Mutations, and Strategies for Effective Management.

INTRODUCTION: The global spread of Trichophyton indotineae presents a pressing challenge in dermatophytosis management. This systematic review explores the current landscape of T. indotineae infections, emphasizing resistance patterns, susceptibility testing, mutational analysis, and management strategies. METHODS: A literature search was conducted in November 2023 using Embase, PubMed, Scopus, and Web of Science databases. Inclusion criteria covered clinical trials, observational studies, case series, or case reports with T. indotineae diagnosis through molecular methods. Reports on resistance mechanisms, antifungal susceptibility testing, and management were used for data extraction. RESULTS AND DISCUSSION: A total of 1148 articles were identified through the systematic search process, with 45 meeting the inclusion criteria. The global spread of T. indotineae is evident, with cases reported in numerous new countries in 2023. Tentative epidemiological cut-off values (ECOFFs) suggested by several groups provide insights into the likelihood of clinical resistance. The presence of specific mutations, particularly Phe397Leu, correlate with higher minimum inhibitory concentrations (MICs), indicating potential clinical resistance. Azole resistance has also been reported and investigated in T. indotineae, and is a growing concern. Nevertheless, itraconazole continues to be an alternative therapy. Recommendations for management include oral or combination therapies and individualized approaches based on mutational analysis and susceptibility testing. CONCLUSION: Trichophyton indotineae poses a complex clinical scenario, necessitating enhanced surveillance, improved diagnostics, and cautious antifungal use. The absence of established clinical breakpoints for dermatophytes underscores the need for further research in this challenging field.

Concepts, Terminology, and Innovations in Follicular Unit Excision Hair Restoration Surgery.

Follicular unit excision (FUE) has emerged as the preferred method for hair transplants. Standardized terms and definitions established by members of the International Society of Hair Restoration Surgery and prominent hair restoration surgeons have become the standard, enabling effective knowledge sharing. This chapter provides an overview of the terminology relating to the field.The historical evolution of FUE and its pivotal role in modern hair transplantation is summarized. Anatomical terminology and graft-related definitions follow, providing insights into the scalp's complex structures and graft characteristics. The subsequent sections detail the terminology associated with graft excision and extraction, shedding light on the precise techniques and procedures employed. An exploration of various FUE techniques and the evolving landscape of FUE devices underscores the continual refinement of hair restoration practices. The chapter proceeds to discuss the "safe'" scalp donor zones, donor assessment terminology, and elements in identifying the optimal donor area for a successful FUE procedure. Additionally, punch dynamics and technique characteristics are examined, emphasizing their pivotal role in achieving superior FUE outcomes. The chapter concludes by discussing the classification of punches and graft evaluation terms, offering insights into the tools, and criteria used to assess graft quality and viability.

Factors Associated With Musculoskeletal Pain Among Hair Transplant Surgeons: Analyses of Survey Data and Review of the Literature.

BACKGROUND: The prevalence of work-related musculoskeletal disorders (WRMD) is increasing among all surgical specialties. OBJECTIVE: Results of a cross-sectional survey of hair transplant surgeons were analyzed, with the aims to (1) determine the prevalence of WRMD, (2) assess risk factors associated with musculoskeletal (MSK) symptoms, and (3) identify mitigation measures. MATERIALS AND METHODS: A survey pertaining to demographics, MSK-related symptoms and its impacts, and pain mitigation measures taken, if any, were distributed to 834 hair transplant surgeons. Risk factors associated with pain severity were assessed using linear regression. RESULTS: Overall, 78.5% (73 of 93) respondents had experienced pain when performing surgery. Musculoskeletal symptoms were most severe in the neck, followed by upper/lower back, and extremities. Number of grafts performed per session of follicular unit extraction positively correlated with pain severity; female surgeons and surgeons aged >71 years were at higher risk. A majority expressed concern that WRMD may limit their career and agreed to a need for improved workplace education. Strength training and ergonomic improvements of surgical procedure were not commonly adopted. CONCLUSION: In sum, WRMD can be debilitating in health care professionals. Workplace ergonomic adjustments and physical exercise programs may be warranted to better mitigate MSK symptoms.

Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase-4 inhibitors.

Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side-effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase-4 (PDE-4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE-4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long-term studies could shed light on the utility of the newer agents in altering the progression of AA.

Strategies for the enhancement of nail plate permeation of drugs to treat onychomycosis.

Onychomycosis is caused by dermatophytes, non-dermatophytes and yeasts. It has a global prevalence of 5.5%, requires long treatment periods, and has high relapse rates following therapy. Oral antifungals are generally the most common treatment. While effective, they have limitations such as drug-drug interactions, hepatotoxicity and adverse side effects; thus, they cannot be used in several populations. Topical antifungals do not have the safety limitations but are typically not as effective. The primary challenge of topical treatment is the permeation of drug molecules across the nail plate barrier, which is a highly cross-linked keratin network. The use of drugs and formulations with favourable characteristics such as small size, absence of lipophilicity, hydrophilic nature, hydrating properties and appropriate pH can greatly improve permeation. Here, we review physical, nanoparticle-based, formulation-based, mechanical and chemical drug delivery strategies to improve the permeation of drugs across the nail plate.

Harnessing the physicochemical properties of DNA as a multifunctional biomaterial for biomedical and other applications.

The biological purpose of DNA is to store, replicate, and convey genetic information in cells. Progress in molecular genetics have led to its widespread applications in gene editing, gene therapy, and forensic science. However, in addition to its role as a genetic material, DNA has also emerged as a nongenetic, generic material for diverse biomedical applications. DNA is essentially a natural biopolymer that can be precisely programed by simple chemical modifications to construct materials with desired mechanical, biological, and structural properties. This review critically deciphers the chemical tools and strategies that are currently being employed to harness the nongenetic functions of DNA. Here, the primary product of interest has been crosslinked, hydrated polymers, or hydrogels. State-of-the-art applications of macroscopic, DNA-based hydrogels in the fields of environment, electrochemistry, biologics delivery, and regenerative therapy have been extensively reviewed. Additionally, the review encompasses the status of DNA as a clinically and commercially viable material and provides insight into future possibilities.

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.

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.

An update on antifungal resistance in dermatophytosis.

INTRODUCTION: The reports of resistance to antifungal agents used for treating onychomycosis and other superficial fungal infections are increasing. This rise in antifungal resistance poses a public health challenge that requires attention. AREAS COVERED: This review explores the prevalence of dermatophytes and the current relationship between dermatophyte species, their minimum inhibitory concentrations (MICs) for terbinafine (an allylamine) and itraconazole (an azole), and various mutations prevalent in these species. The most frequently isolated dermatophyte associated with resistance in patients with onychomycosis and dermatophytosis was T. mentagrophytes. However, T. indotineae emerged as the most prevalent isolate with mutations in the SQLE gene, exhibiting the highest MIC of 8 µg/ml for terbinafine and MICs of 8 µg/ml and ≥ 32 µg/ml for itraconazole.Overall, the most prevalent SQLE mutations were Phe397Leu, Leu393Phe, Ala448Thr, Phe397Leu/Ala448Thr, and Lys276Asn/Leu415Phe (relatively recent). EXPERT OPINION: Managing dermatophyte infections requires a personalized approach. A detailed history should be obtained including details of travel, home and occupational exposure, and clinical examination of the skin, nails and other body systems. Relevant testing includes mycological examination (traditional and molecular). Additional testing, where available, includes MIC evaluation and detection of SQLE mutations. In case of suspected terbinafine resistance, itraconazole or voriconazole (less commonly) should be considered.

Pattern hair loss and health care professionals: How well are we connecting with our audience?

BACKGROUND: Pattern hair loss, the most common form of hair loss, affects millions in the United States. Americans are increasingly seeking health information from social media. It would appear that healthcare professionals contribute relatively minimally to pattern hair loss content, thereby posing serious concerns for credibility and quality of information available to the general public. OBJECTIVES: This study evaluates popular pattern hair loss-related content on Instagram, TikTok, and YouTube, aiming to understand effective engagement strategies for healthcare professionals on social media. METHODS: The top 60 short-form videos were extracted from Instagram, TikTok, and YouTube, using the search term "pattern hair loss" and inclusion of USA-based accounts only. Videos were categorized by creator type (healthcare vs. non-healthcare professional), content type (informational, interactional, and transactional), and analyzed for user engagement and quality, using engagement ratios and DISCERN scores, respectively. CONCLUSIONS: Healthcare professionals, especially dermatologists, play a crucial role in delivering credible information on social media, supported by higher DISCERN scores. Multi-platform presence, frequent activity, and strategic content creation contributes to increased reach and engagement. Duration of short-form videos does not impact engagement. The "Duet" or "Remix" options on TikTok, Instagram, and YouTube serve as a valuable tool for healthcare professionals to counter misinformation. Our study underscores the importance of optimizing educational impact provided by health care professionals at a time when the public increasingly relies on social media for medical information.

Effectiveness and safety of oral terbinafine for dermatophyte distal subungual onychomycosis.

INTRODUCTION: Terbinafine has been a cornerstone in dermatophyte infection treatment. Despite its global efficacy, the emergence of terbinafine resistance raises concerns, requiring ongoing vigilance. AREAS COVERED: This paper focuses on evaluating the efficacy and safety of terbinafine in treating dermatophyte toenail infections. Continuous and pulse therapies, with a 24-week continuous regimen and a higher dosage of 500 mg/day have demonstrated superior efficacy to the FDA approved regimen of 250 mg/day x 12 weeks. Pulse therapies, though showing comparable effectiveness, present debates with regards to their efficacy as conflicting findings have been reported. Safety concerns encompass hepatotoxicity, gastrointestinal, cutaneous, neurologic, hematologic and immune adverse-effects, and possible drug interactions, suggesting the need for ongoing monitoring. EXPERT OPINION: Terbinafine efficacy depends on dosage, duration, and resistance patterns. Continuous therapy for 24 weeks and a dosage of 500 mg/day may enhance outcomes, but safety considerations and resistance necessitate individualized approaches. Alternatives, including topical agents and alternative antifungals, are to be considered for resistant cases. Understanding the interplay between treatment parameters, adverse effects, and resistance mechanisms is critical for optimizing therapeutic efficacy while mitigating resistance risks. Patient education and adherence are vital for early detection and management of adverse effects and resistance, contributing to tailored and effective treatments.

Efinaconazole 10% solution: a comprehensive review of its use in the treatment of onychomycosis.

INTRODUCTION: Onychomycosis is an infection of the nail bed and the nail plate. While oral antifungals are first-line for moderate-to-severe onychomycosis, topical efinaconazole 10% solution (JUBLIA®; Clenafin®) is effective and safe for mild-to-moderate severity onychomycosis. It is FDA-approved for patients aged 6 years and above. AREAS COVERED: This literature review includes pharmacokinetics, microbiology, efficacy, safety, and post-marketing surveillance. It demonstrates consistent safety and efficacy across diverse patient demographics and comorbidities, including pediatric, diabetic and the elderly populations, without systemic side effects or drug interactions. EXPERT OPINION: Efinaconazole 10% solution is an important addition to the armamentarium of therapies available to treat onychomycosis. Certain subgroups respond particularly well: females versus males, children versus adults, early onset onychomycosis (<1-year disease), those with mild onychomycosis (≤25% nail involvement), absence of tinea pedis, and thin nail plates at baseline (<1 mm thickness). Efinaconazole 10% solution is effective in diabetics and has demonstrated efficacy against dermatophytomas. Efinaconazole may be a consideration when terbinafine resistance is a concern, due to its different target of action.

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.

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.

Infants who develop autism show smaller inventories of deictic and symbolic gestures at 12 months of age.

Gestures are an important social communication skill that infants and toddlers use to convey their thoughts, ideas, and intentions. Research suggests that early gesture use has important downstream impacts on developmental processes, such as language learning. However, autistic children are more likely to have challenges in their gestural development. The current study expands upon previous literature on the differences in gesture use between young autistic and non-autistic toddlers by collecting data using a parent-report questionnaire called the MCDI-Words and Gestures at three time points, 12, 18, and 24 months of age. Results (N = 467) showed that high-likelihood infants who later met diagnostic criteria for ASD (n = 73 HL-ASD) have attenuated gesture growth from 12 to 24 months for both deictic gestures and symbolic gestures when compared to high-likelihood infants who later did not meet criteria for ASD (n = 249 HL-Neg) and low-likelihood infants who did not meet criteria for ASD (n = 145 LL-Neg). Other social communicative skills, like play behaviors and imitation, were also found to be impacted in young autistic children when compared to their non-autistic peers. Understanding early differences in social communication growth before a formal autism diagnosis can provide important insights for early intervention.

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.