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.

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.

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.

Natural products for male androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common cause of hair loss in men, often requiring medical attention. The US FDA approved topical minoxidil and oral finasteride to treat AGA. Topical minoxidil requires a long-term application to observe improvement; oral finasteride may cause undesirable side effects. Therefore, natural products may be an alternative when patients are skeptical about these two conventional treatments. Physicians may also suggest natural products in conjunction with topical minoxidil or oral finasteride to enhance clinical outcomes. This article reviews the prospect of natural products in treating male AGA. A systematic search was conducted in PubMed, CINAHL, Scopus, Web of Science, and EMBASE (Ovid) on July 19, 2021. In addition, the bibliographies of selected articles were hand-searched to identify relevant studies. After deduplication and screening, 11 clinical studies meet the criteria for detailed review. The selected clinical studies suggest that saw palmetto, caffeine, melatonin, marine extracts, rosemary oil, procyanidin, pumpkin seed oil, and cannabidiol oil might be considered in male AGA treatment.

Management of tinea capitis in Israel: A comparative study.

BACKGROUND: Tinea capitis is a common fungal infection in Israel, most commonly caused by the dermatophyte Trichophyton tonsurans. OBJECTIVES: To investigate the effectiveness of oral antifungal monotherapy in producing clinical or complete cure. We also evaluated the impact of topical therapy (bifonazole 1% shampoo and/or betamethasone valerate 0.1% solution), prior to oral treatment, on patients' likelihood of clinical or complete cure. METHODS: A retrospective chart review was conducted. Patients with mycologically confirmed tinea capitis were treated with one of four regimens: (1) terbinafine (greater than 40 kg: 250 mg/day, 20 to 40 kg: 125 mg/day, less than 20 kg: 62.5 mg/day), (2) itraconazole 5 mg/kg daily, (3) fluconazole 6 mg/kg daily, or (4) griseofulvin 20 mg/kg daily. We used generalized linear models (GLM) to determine whether there was a significant association between the odds of cure and choice of treatment. RESULTS: The causative species was Trichophyton tonsurans in all but 6 cases that grew T violaceum. For pediatric patients, the odds of having complete or clinical cure within 6 weeks was greater if they used terbinafine compared to itraconazole, fluconazole, or griseofulvin (odds ratio [OR] = 9.06, P = .047). The likelihood of complete or clinical cure within 8 weeks of oral therapy was lower if topical steroids were previously used compared to if topical antifungals were used prior to systemic treatment (OR = 0.29, P = .046). CONCLUSIONS: Our findings substantiate prior literature demonstrating that terbinafine is non-inferior to griseofulvin, itraconazole, and fluconazole in the therapy of pediatric tinea capitis caused by T tonsurans.

Factors influencing the effect of photobiomodulation in the treatment of androgenetic alopecia: A systematic review and analyses of summary-level data.

Low-level laser therapy (LLLT) is used to treat androgenetic alopecia (AGA). The therapeutic effect of LLLT on AGA has been evaluated; however, there is a paucity of studies that investigated device- and usage-related factors that may influence the effect of LLLT on hair regrowth. The literature was systematically searched to identify eligible studies; PubMed, Scopus, EMBASE and clinicaltrials.gov databases were searched on 30 April 2020. Eligible studies were randomized trials that investigated the effect of LLLT on hair density in AGA. Robust linear regressions were used to make comparisons. An increase in the per-session energy fluence by 1 J/cm2 is significantly associated with an increase in hair density by 0.23 hairs/cm2 (95% CI: 0.21 hairs/cm2 , 0.25 hairs/cm2 ). The number of laser or light-emitting diodes is not significantly associated with change in hair density. Increasing the total duration of exposure to treatment is associated with a significant increase in hair density (ß = .53, P < .05). Switching from continuous to pulse irradiation was associated with a significant increase in hair density (ß = 10.11, P < .01). Energy fluence, irradiation session duration, and light pulsing have a significant therapeutic effect on AGA, while the number of diodes does not.

A network meta-analysis on the efficacy and safety of monotherapies for tinea capitis, and an assessment of evidence quality.

Various monotherapies exist for tinea capitis; however, their relative efficacies have never been determined using a statistical approach which compares treatments' efficacy simultaneously. The goal of this study was to determine the relative efficacy (mycologic and complete cure rates) of monotherapies for the treatment of tinea capitis. On October 5, 2019, searches were performed in Scopus, PubMed, EMBASE, MEDLINE (Ovid), and CINAHL; there were no date restrictions. For the main network meta-analysis, eligible studies were randomized trials that investigated the effect of tinea capitis monotherapies on subjects' mycological and complete cure rates. Network meta-analyses were conducted in accordance with the 2015 Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist for network meta-analyses. Mycological cure rate was the primary outcome; complete cure rate and adverse events were secondary outcomes. Twelve studies met the eligibility criteria for the main network; five systemic monotherapies were identified, griseofulvin, ketoconazole, terbinafine, itraconazole, and fluconazole. When the causative species was of the Microsporum genus, griseofulvin was most efficacious in terms of mycological cure (SUCRA = 66.1%) and complete cure (SUCRA = 80.6%). For tinea capitis caused by the Trichophyton species, terbinafine was the most efficacious in terms of both mycological and complete cure (SUCRA values of 75.2% and 78.2%, respectively). Risk of adverse events did not significantly differ across the interventions. Our results are congruent with those of previous pairwise meta-analyses; our findings also corroborate clinical experience and anecdotal evidence.

Recently reported familial hypercholesterolemia-related mutations from cases in the Middle East and North Africa region.

PURPOSE OF REVIEW: Familial hypercholesterolemia is an inherited disorder where cases have a significantly higher risk of having premature myocardial infarction than noncases. The prevalence of this genetic disease is currently unknown in countries of the Middle East and North Africa region. Given that a high percentage of marriages are consanguineous in this region, the prevalence may be much higher than assumed. We systematically reviewed the literature to identify case-related mutations reported within the last 4 years and since our first report in 2014. RECENT FINDINGS: Mutations were reported in familial hypercholesterolemia cases from the Saudi, Iranian, Lebanese, and Syrian populations. Some of the mutations were novel and a variety of familial hypercholesterolemia genotypes were identified, such as compound heterozygotes and double heterozygotes. SUMMARY: In recent years, work has been done to identify familial hypercholesterolemia cases in various countries of the Middle East and North Africa region. With regards to the prospective familial hypercholesterolemia registry for the Middle East and North Africa region, an important goal for the near future would be to have physician specialists collaborate with primary care clinicians for the identification and optimal care of familial hypercholesterolemia cases.

A meta-analysis study on the association between smoking and male pattern hair loss.

BACKGROUND: Smoking-which often refers to recreational consumption of the nicotine-containing tobacco-is deemed a risk factor for both the development of and worsening of androgenetic alopecia (AGA). However, there is no published meta-analysis study on the effect of smoking on AGA; so, we quantitatively synthesized the evidence base pertaining to the recreational activity and this form of hair loss in men. METHODS: We systematically searched PubMed and Scopus to identify published studies with suitable data, and pairwise meta-analyses were conducted. RESULTS: Our search identified eight studies-and the data thereof were used across four meta-analyses. We found that ever smokers are significantly (p < 0.05) more likely, than never smokers, to develop AGA (pooled odds ratio (OR) = 1.82, 95% confidence interval (CI): 1.55-2.14). Our results showed that the odds of developing AGA are significantly (p < 0.05) higher in men who smoke at least 10 cigarettes per day, than in their counterparts who smoke up to 10 cigarettes per day (pooled OR = 1.96, 95% CI: 1.17-3.29). For men with AGA, the odds of disease progression are significantly (p < 0.05) higher among ever smokers than in never smokers (pooled OR = 1.27, 95% CI: 1.01-1.60). We found no significant (p ≥ 0.05) association between smoking intensity and disease progression. CONCLUSIONS: Findings from the current study-which is the first meta-analysis to our knowledge reviewing the association between AGA and the extent of smoking, can guide further research and update clinical practice guidelines.

The relative effect of monotherapy with 5-alpha reductase inhibitors and minoxidil for female pattern hair loss: A network meta-analysis study.

BACKGROUND: Minoxidil and the 5-alpha reductase inhibitors (5-ARIs), specifically, dutasteride and finasteride, are usually used to treat pattern hair loss (PHL), but evidence on the relative effectiveness of these drugs is far less for women than men. AIMS: We performed an age-adjusted network meta-analysis (NMA) to determine the comparative efficacy of monotherapy with the three agents-in any dosage and administrative route-on PHL in adult women. METHODS: The peer-reviewed literature was systematically reviewed to obtain data for our NMA. The outcome measure for our NMA was "change in total hair density." We referred to "regimen" as an "agent and its dosage;" our Bayesian NMA estimated regimens' surface under the cumulative ranking curve (SUCRA) values and pairwise relative effects. RESULTS: Our NMA used data from 13 trials-across which the following 10 regimens were identified (in decreasing order of SUCRA): 5 mg/day finasteride for 24 weeks (SUCRA = 95.7%), 5% topical minoxidil solution twice daily for 24 weeks (SUCRA = 89.5%), 1 mg/day minoxidil for 24 weeks (SUCRA = 78.1%), 5% topical minoxidil foam 1 half capful/day for 24 weeks (SUCRA = 66.5%), 3% topical minoxidil solution 1 mL twice daily for 24 weeks (SUCRA = 45.1%), 2% topical minoxidil solution 1 mL twice daily for 24 weeks (SUCRA = 44.6%), 5% topical minoxidil solution 1 mL/day for 24 weeks (SUCRA = 41.7%), 0.25 mg/day minoxidil for 24 weeks (SUCRA = 35.5%), 1.25 mg/day finasteride for 24 weeks (SUCRA = 24.8%) and 1 mg/day finasteride for 24 weeks (SUCRA = 4.3%). CONCLUSION: Our findings can improve clinical guidelines and help dermatologists manage female PHL more optimally with the available options.

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.

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.

Effect of the Intralesional Forms of Methylprednisolone Acetate and Methotrexate on Psoriatic Nails.

Individuals with psoriatic nails often have a lower quality of life relative to their counterparts with healthy nails. Methotrexate (MTX), an anti-neoplastic agent, is a longstanding treatment option for nail psoriasis. In the current study, we compared the effects of MTX to that of a corticosteroid, namely, methylprednisolone acetate (i.e., Depo-Medrol®) across individuals with nail psoriasis. We used a cohort study design, and both agents were administered intralesionally. Outcome variables were based on the Nail Psoriasis Severity Index (NAPSI). We quantified the effect in terms of change in NAPSI, complete cure at week 16, and cure between 32 and 36 weeks. Our regressions demonstrated that reduced NAPSI scores with Depo-Medrol were, on average, greater than that with MTX by 2.27 (n = 48, P = 0.000255) at week 16. Similarly, the odds of complete cure at week 16 was greater with Depo-Medrol® than with MTX (odds ratio = 18.6, P < 0.0001). In terms of both complete cure and change in NAPSI, Depo-Medrol® was significantly more effective than MTX at a follow-up period of 32-36 weeks. Our study established that intralesional Depo-Medrol® is more effective than intralesional methotrexate for treating nail psoriasis.

The relative efficacy of monotherapy with Janus kinase inhibitors, dupilumab and apremilast in adults with alopecia areata: Network meta-analyses of clinical trials.

BACKGROUND: Janus kinase (JAK) inhibitors, biologics, and phosphodiesterase-4 (PDE-4) inhibitors are recent therapies for alopecia areata (AA)-albeit, knowledge gaps exist for these agents' relative efficacy. OBJECTIVES: We determined the relative efficacy and safety of monotherapy with the aforementioned agents in adults with AA. METHODS: The literature was systematically searched; we used data from randomized trials that investigated the agents' efficacy-as per Severity of Alopecia Tool (SALT) scores. Bayesian network meta-analyses were used to determine relative efficacy and safety. Effect modification was determined using a generalized linear model on aggregate data; evidence quality was evaluated. RESULTS: Based on the surface under the cumulative ranking curve estimates obtained from multiple efficacy endpoints, regimens with the highest likelihood of achieving percent reduction in SALT scores, as well as a minimum 90%, 75% or 50% reduction in SALT scores are (in alphabetical order) baricitinib 4 mg once daily (QD), brepocitinib 60/30 mg QD, deuruxolitinib (CTP-543) 12 mg twice daily (BID), ritlecitinib 200/50 mg QD, ruxolitinib 20 mg BID and tofacitinib 5 mg BID. In contrast, dupilumab subcutaneous injections administered weekly and apremilast 30 mg BID were less likely to be effective. Discontinuation due to any adverse event was the least likely with oral JAK inhibitors, and more likely with dupilumab and apremilast. CONCLUSIONS: Our results support the conduct of high-quality comparative trials to determine whether JAK inhibitors are more effective and safer than PDE4 inhibitors.

Relative Effects of Minoxidil 5%, Platelet-Rich Plasma, and Microneedling in Pattern Hair Loss: A Systematic Review and Network Meta-Analysis.

Background: Combination treatments may improve the utility of approved agents for the treatment of pattern hair loss (PHL); however, head-to-head comparisons are lacking. Objective: The aim of the study was to compare the efficacy of 5% minoxidil, platelet-rich plasma (PRP), and microneedling across adults with PHL insofar as change in total hair density at 24 weeks. Methods: We conducted a literature search in July 2022. Through our Bayesian network meta-analysis, we estimated treatments' surface under the cumulative ranking distribution (SUCRA) values and relative effects - in terms of mean difference (MD). Results: Data from 27 trials, totaling 1,110 patients, were extracted. Interventions were ranked based on the probability of inducing hair density improvements: 5% minoxidil plus microneedling (SUCRA = 95.8%), 5% minoxidil plus PRP (SUCRA = 64.7%), 5% minoxidil (SUCRA = 53.9%), PRP (SUCRA = 34.9%), microneedling (SUCRA = 27.8%), and PRP with microneedling (SUCRA = 22.9%). The efficacy of 5% minoxidil plus microneedling in improving total hair density was significantly greater (p < 0.05) than 5% minoxidil monotherapy (MD = 13 hairs/cm2), PRP monotherapy (MD = 16 hairs/cm2), and microneedling monotherapy (MD = 17 hairs/cm2). Conclusion: Five percent minoxidil plus microneedling is an effective treatment option for improving hair density at 6 months in adult PHL patients.

Efficacy of non-surgical treatments for androgenetic alopecia in men and women: a systematic review with network meta-analyses, and an assessment of evidence quality.

BACKGROUND AND OBJECTIVE: Various treatments exist for androgenetic alopecia (AGA); we determined the relative efficacies of non-surgical AGA monotherapies separately for men and women. METHODS: Randomized controlled trials (RCTs) were systematically searched in PubMed, EMBASE, Scopus and clinicaltrials.gov. Separate networks were used for men and women; for each network, a Bayesian network meta-analysis (NMA) of mean change in hair count from baseline (in units of hairs per square centimeter) was performed using a random effects model. RESULTS: The networks for male and female AGA included 30 and 10 RCTs, respectively. We identified the following treatments for male AGA in decreasing rank of efficacy: platelet-rich plasma (PRP), low-level laser therapy (LLLT), 0.5 mg dutasteride, 1 mg finasteride, 5% minoxidil, 2% minoxidil, and bimatoprost. For female AGA the following were identified in decreasing rank of efficacy: LLLT, 5% minoxidil, and 2% minoxidil. The evidence quality of the highest ranked therapies, for male and female AGA, was judged to be low. CONCLUSIONS: While newer treatments like LLLT may be more efficacious than more traditional therapies like 5% minoxidil, the efficacy of the more recent treatment modalities needs to be further validated by future RCTs.

The effect of placebo in split-scalp and whole-head platelet-rich plasma trials for androgenetic alopecia differs: Findings from a systematic review with quantitative evidence syntheses.

BACKGROUND: Some studies have shown that platelet-rich plasma (PRP) improves androgenetic alopecia (AGA), while others do not. We determined whether the placebo effect significantly varies between split-scalp and whole-head trials on PRP monotherapy for AGA. Our rationale was based on the plausibility of PRP diffusing to the control (i.e., "placebo") side of split-scalp trials. This is not possible in whole-head studies. METHODS: We systematically searched the literature for available data. Our choice of analyses and outcomes were determined by the available data. RESULTS: Our endpoint was change in total hair density 6 months after baseline. Our regression showed that total hair density after 6 months was significantly (p < 0.05) higher in the placebo arm of split-scalp trials, compared to whole-head studies, by 37 hairs/cm2 . Our one-arm meta-analyses showed that the pooled change in total hair density between the PRP side and placebo side in split-scalp studies was -3 hairs/cm2 (p = 0.37), that is, a slight decrease in hair density in the placebo side of the scalp. For whole-head studies, the corresponding difference in total hair density between patients receiving PRP and those on placebo was -30 hairs/cm2 (p = 0.000017), that is, a much larger decrease in hair density. Patients in the placebo group in whole-head trials lost significantly more hair than in the placebo side of the split-head trials where hair loss was comparatively reduced - presumably because of PRP diffusing from the treatment side of the scalp. CONCLUSIONS: The association between design (i.e., split-scalp vs. whole-head) and outcome, in placebo arms of AGA trials on PRP monotherapy, had never been reported. This "design effect" could partly reconcile the incongruent conclusions across the PRP literature for AGA; furthermore, clinical guidelines can consider "design effect" when selecting evidence to base care practices on.

There Is a Positive Dose-Dependent Association between Low-Dose Oral Minoxidil and Its Efficacy for Androgenetic Alopecia: Findings from a Systematic Review with Meta-Regression Analyses.

Background: Recently, low-dose oral minoxidil (LDOM) has entered the landscape of therapies for androgenetic alopecia (AGA). We determined whether using LDOM is associated with improving AGA in a dose-dependent manner; secondarily, we examined whether a dose-dependent association also exists for safety. Methods: Systematic searches were conducted in PubMed and Scopus to identify studies that would be eligible for our quantitative analyses; the logistics of our analyses was determined by the data we gathered. Results: Six studies were eligible for quantitative analyses; we conducted meta-regressions. We found that, for persons with AGA, increasing the dosage of LDOM by 1 mg/day was - after six months - significantly associated with an expected sex-adjusted increase in hair diameter (mean difference = 1.4 µm, p = 0.01), total hair density (mean difference = 47.1 hairs/cm2, p = 0.007), terminal hair density (mean difference = 9.1 hairs/cm2, p = 0.001), risk of hypertrichosis (mean difference = 17.9%, p = 0.006), and cardiovascular adverse events (mean difference = 4.8%, p = 0.004). Conclusions: Our study produced new evidence as our work is the first to show a positive dose-dependent association between the use of LDOM and change in hair diameter, hair density, risk of hypertrichosis, and cardiovascular adverse events for persons with AGA. Future randomized trials could produce causal evidence that would corroborate these dose-dependent associations.

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.