Brote de dermatofitosis en región de cabeza y cuello asociadas al rasurado en peluquerías: estudio descriptivo multicéntrico de una serie de casos / Outbreak of Dermatophyte Infections on the Head and Neck Related to Shave Haircuts: Description of a Multicenter Case Series

Introducción Desde 2021 se ha detectado un aumento de casos de tiñas del cuero cabelludo en adolescentes que se cortan el pelo mediante rasurado o degradado. Pacientes y métodos Estudio observacional retrospectivo multicéntrico de casos de dermatofitosis del polo cefálico con el antecedente de haber sido contraídas tras el rasurado frecuente en peluquería. Se realizó una llamada a dermatólogos de la Academia Española de Dermatología y Venereología (AEDV) para que aportaran casos observados entre enero de 2021 y diciembre de 2022. Se incluyeron pacientes con confirmación microbiológica mediante cultivo o examen directo con KOH. Resultados Se recogieron 107 casos, siendo 106 pacientes varones. Se observaron 78 formas no inflamatorias frente a 29 inflamatorias. El hongo aislado con mayor frecuencia fue Trichophyton tonsurans (75,7% de los casos). Las lesiones aparecieron predominantemente en la nuca y en el área temporal. Conclusiones La distribución por sexo, edad y localización lesional parece apuntar a que una nueva tendencia social, en la que adolescentes varones acuden asiduamente a peluquerías para el afeitado de las zonas occipital y temporal, sería la causante de esta agrupación de casos de tiña del cuero cabelludo. El microorganismo más frecuente en nuestro estudio (T.tonsurans) coincide con el más prevalente en nuestro medio. Con el presente estudio se evidencia un acúmulo de casos susceptible de ser tenido en cuenta por organismos competentes de salud pública, a los cuales corresponde velar por el cumplimiento de las normas de desinfección del material empleado para el rasurado (AU)

Introduction Since 2021, an increase in cases of tinea capitis has been detected in adolescents who shave their hair with fade haircut. Patients and methods Multicenter retrospective observational study of cases of cephalic pole dermatophytosis with a history of having been acquired after frequent shaving in hairdressing. A call was made to dermatologists from the Spanish Academy of Dermatology and Venereology (AEDV) to provide cases observed between January 2021 and December 2022. Patients with microbiological confirmation by culture or direct examination with KOH were included. Results 107 cases were collected, 106 of which were male. 78 non-inflammatory forms were observed, compared to 29 inflammatory. The most frequently isolated fungus was Trichophyton tonsurans (75.7% of cases). The lesions appeared predominantly on the nape of the neck and temporal area. Conclusions The distribution by sex, age and lesional location seems to indicate that a new social trend, in which male adolescents regularly go to hairdressers to shave the occipital and temporal areas, would be the cause of this grouping of cases of ringworm of the scalp. The most frequent microorganism in our study (T.tonsurans) coincides with the most prevalent in our environment. This study shows an accumulation of cases that can be taken into account by competent Public Health agencies, which are responsible for ensuring compliance with the rules of disinfection of the material used for shaving (AU)

[Translated article] Outbreak of Dermatophyte Infections on the Head and Neck Related to Shave Haircuts: Description of a Multicenter Case Series / Brote de dermatofitosis en región de cabeza y cuello asociadas al rasurado en peluquerías: estudio descriptivo multicéntrico de una serie de casos

Introduction Since 2021, an increase in cases of tinea capitis has been detected in adolescents who shave their hair with fade haircut. Patients and methods Multicenter retrospective observational study of cases of cephalic pole dermatophytosis with a history of having been acquired after frequent shaving in hairdressing. A call was made to dermatologists from the Spanish Academy of Dermatology and Venereology (AEDV) to provide cases observed between January 2021 and December 2022. Patients with microbiological confirmation by culture or direct examination with KOH were included. Results 107 cases were collected, 106 of which were male. 78 non-inflammatory forms were observed, compared to 29 inflammatory. The most frequently isolated fungus was Trichophyton tonsurans (75.7% of cases). The lesions appeared predominantly on the nape of the neck and temporal area. Conclusions The distribution by sex, age and lesional location seems to indicate that a new social trend, in which male adolescents regularly go to hairdressers to shave the occipital and temporal areas, would be the cause of this grouping of cases of ringworm of the scalp. The most frequent microorganism in our study (T.tonsurans) coincides with the most prevalent in our environment. This study shows an accumulation of cases that can be taken into account by competent Public Health agencies, which are responsible for ensuring compliance with the rules of disinfection of the material used for shaving (AU)

Introducción Desde 2021 se ha detectado un aumento de casos de tiñas del cuero cabelludo en adolescentes que se cortan el pelo mediante rasurado o degradado. Pacientes y métodos Estudio observacional retrospectivo multicéntrico de casos de dermatofitosis del polo cefálico con el antecedente de haber sido contraídas tras el rasurado frecuente en peluquería. Se realizó una llamada a dermatólogos de la Academia Española de Dermatología y Venereología (AEDV) para que aportaran casos observados entre enero de 2021 y diciembre de 2022. Se incluyeron pacientes con confirmación microbiológica mediante cultivo o examen directo con KOH. Resultados Se recogieron 107 casos, siendo 106 pacientes varones. Se observaron 78 formas no inflamatorias frente a 29 inflamatorias. El hongo aislado con mayor frecuencia fue Trichophyton tonsurans (75,7% de los casos). Las lesiones aparecieron predominantemente en la nuca y en el área temporal. Conclusiones La distribución por sexo, edad y localización lesional parece apuntar a que una nueva tendencia social, en la que adolescentes varones acuden asiduamente a peluquerías para el afeitado de las zonas occipital y temporal, sería la causante de esta agrupación de casos de tiña del cuero cabelludo. El microorganismo más frecuente en nuestro estudio (T.tonsurans) coincide con el más prevalente en nuestro medio. Con el presente estudio se evidencia un acúmulo de casos susceptible de ser tenido en cuenta por organismos competentes de salud pública, a los cuales corresponde velar por el cumplimiento de las normas de desinfección del material empleado para el rasurado (AU)

Treatment of difficult-to-treat-dermatophytosis: results of a randomized, double-blind, placebo-controlled study.

INTRODUCTION: Difficult-to-treat dermatophytosis is an emerging public health problem in Sri Lanka. Safe, effective and affordable treatment is needed to solve this problem. Therefore this study has assessed the effectiveness and safety of modified Whitfield ointment applied twice daily with oral griseofulvin 500 mg daily given over 8 weeks in patients with difficult-to-treat dermatophytosis. METHODOLOGY: A randomized, double-blind, within-patient-placebo-controlled trial was conducted in patients with clinico- mycologically (history, physical examination, direct light microscopy examination of scales in potassium hydroxide mount) confirmed difficult-to-treat dermatophytosis. Lesions were randomized to receive modified Whitfield ointment (5% benzoic acid and 5% salicylic acid) or emulsifying ointment. All patients were given oral griseofulvin 500mg once daily. The outcome measures were clinical assessment of disease severity, the total surface area of the lesions and the patient's perception of the disease severity at baseline and every two weeks up to a maximum of 8 weeks. RESULTS: Thirty patients completed the study. At two weeks, there was a statistically significant improvement in modified Whitfield ointment arm in the clinical assessment of disease severity and the patients' perception. There was a 7.59% reduction in the surface area of lesions in modified Whitfield ointment arm and a 5.83% increase in the surface area of lesions in the emulsifying ointment arm at two weeks. The difference between the two arms in surface area changes was not statistically significant (p = 0.107, df = 29). CONCLUSIONS: A combination of modified Whitfield ointment with griseofulvin is significantly effective, safe and affordable option for treating difficult-to-treat dermatophytosis in the tropics.

Case Report: Extensive Tinea Corporis and Inflammatory Tinea Capitis Caused by the Anthropophilic Dermatophyte Trichophyton tonsurans.

Trichophyton tonsurans is an anthropophilic dermatophyte with a worldwide distribution and is responsible for superficial mycosis with a wide range of clinical manifestations. We report two atypical cases of tinea due to T. tonsurans in two children: a case of extensive tinea corporis and a case of inflammatory tinea capitis.

Generalised papular variant of elastolytic giant cell granuloma.

Elastolytic giant cell granuloma (EGCG), also known as actinic granuloma, is an uncommon granulomatous dermatosis usually characterised by asymptomatic annular plaques on sun-exposed skin. Its aetiology is not fully elucidated, but actinic damage has been considered the main causal factor. Atypical variants with lesions in a non-photodistributed pattern are rare and often related to a systemic disorder, suggesting a more complex pathogenesis and demanding for a screening work-up. Herein, we report a case of an adult obese, diabetic woman presenting with a generalised pruritic papular eruption, histologically revealing an elastolytic giant cell granuloma, with a good response to treatment. In this case, the dermatosis was probably associated with her metabolic comorbidities.

Comparisons of in vitro Fick's first law, lipolysis, and in vivo rat models for oral absorption on BCS II drugs in SNEDDS.

PURPOSE: The objective of this study was to compare the in vitro Fick's first law, in vitro lipolysis, and in vivo rat assays for oral absorption of Biopharmaceutical Classification Systems Class II (BCS II) drugs in self-nanoemulsifying drug delivery system (SNEDDS), and studied drugs and oils properties effects on the absorption. METHODS: The transport abilities of griseofulvin (GRI), phenytoin (PHE), indomethacin (IND), and ketoprofen (KET) in saturated water solutions and SNEDDS were investigated using the in vitro Madin-Darby canine kidney cell model. GRI and cinnarizine (CIN) in medium-chain triglycerides (MCT)-SNEDDS and long-chain triglycerides (LCT)-SNEDDS were administered in the in vivo SD rat and in vitro lipolysis models to compare the oral absorption and the distribution behaviors in GIT and build an in vitro-in vivo correlation (IVIVC). RESULTS: In the cell model, the solubility of GRI, PHE, IND, and KET increased 6-8 fold by SNEDDS, but their permeability were only 18%, 4%, 8%, and 33% of those of their saturated water solutions, respectively. However, in vivo absorption of GRI-SNEDDS was twice that of the GRI suspension and those of CIN-SNEDDS were 15-21 fold those of the CIN suspension. In the lipolysis model, the GRI% in aqueous and pellet phases of MCT were similar to that in LCT. In contrast, the CIN% in the aqueous and pellet phases were decreased but that of the lipid phase increased. In addition, an IVIVC was found between the CIN% in the lipid phase and in vivo relative oral bioavailability (F r). CONCLUSION: The in vitro cell model was still a suitable tool to study drug properties effects on biofilm transport and SNEDDS absorption mechanisms. The in vitro lipolysis model provided superior oral absorption simulation of SNEDDS and helped to build correlation with in vivo rats. The oral drug absorption was affected by drug and oil properties in SNEDDS.

Griseofulvin vs terbinafine for paediatric tinea capitis: When and for how long.

Outbreaks of tinea capitis (TC) can be a source of medical and economic burden for healthcare systems; Griseofulvin and terbinafine are considered to be effective first-line treatments for TC. In order to compare the efficacy of griseofulvin and terbinafine for the treatment of TC in a paediatric population of African immigrants in the Tel Aviv area, we conducted a retrospective cohort study of all cases of TC diagnosed and treated between March 2016 and February 2018 at a dedicated TC paediatric dermatology clinic at the Tel Aviv Medical Center (which serves as a referral centre for the paediatric refugee population in the Tel Aviv metropolitan area). Epidemiologic, clinical and laboratory data were collected, and 304 patients were included. Trichophyton violaceum (TV), Trichophyton soudanense (TS) and Microsporum audouinii (MA) were the prominent causative organisms. Treatment with griseofulvin suspension for 12 weeks was compared with (a) griseofulvin suspension for 8 weeks and with (b) terbinafine tablets for 4 weeks. There was no statistically significant difference between the groups regarding age, sex, country of birth, ethnicity and the causative organism. Twelve weeks of griseofulvin treatment had a statistically significant better cure rate than 4 weeks of terbinafine. Treatment was significantly more effective when TC was due to infections with MA and TS as compared with TV. No statistically significant difference was observed between 12- and 8-week treatment with griseofulvin.

Nano- and microcrystals of griseofulvin subcutaneously administered to rats resulted in improved bioavailability and sustained release.

Griseofulvin is a commonly used antifungal agent which is administered per oral (p.o.). The oral administration route, however, shows rather low bioavailability. The aim of this study was to improve the bioavailability and to evaluate and interpret the pharmacokinetic profiles after subcutaneous (s.c.) administration of crystalline griseofulvin nano- and microsuspensions. Both formulations were injected at 5 and 500 µmol/kg to rats. For the lower concentration, the profiles were similar after s.c. injection but extended as compared to p.o. administration. For the higher concentration, injection of microsuspension resulted in a maintained plateau whereas the nanosuspension resulted in an obvious peak exposure followed by extended elimination. Both suspensions showed improved exposure with dose. The differences in peak exposures between nano- and microparticles, at the high dose, were mainly ascribed to differences in dissolution rate, experimentally determined in vitro, using spectroscopic methods. The extended appearance in the circulation may depend on the physicochemical properties of the compound and the physiological conditions at the injection site. The bioavailability was improved for both formulations compared with an orally administered nanosuspension, suggesting the s.c. route to be a preferred administration option for compounds with low oral bioavailability regarding both overall exposure and extended efficacy.

Sustained release and improved bioavailability in mice after subcutaneous administration of griseofulvin as nano- and microcrystals.

The objective of the study was to evaluate the pharmacokinetic profile after different subcutaneous (s.c.) administrations of nano- and microparticle suspensions of griseofulvin to mice. The solubility of the compound was determined as approximately 40 µM, at 37 °C, independent of particle size, stabilizer mixtures investigated and solvent used for measurement. The present in vivo studies demonstrated non-linear absorption kinetics (in peak concentration, Cmax) for griseofulvin up to 50 mg/kg after s.c. administration of nanocrystals and microsuspensions but linear increase in area under the curve (AUC) at all occasions investigated. Cmax was higher for smaller particles administered. Both investigated suspensions, at 10 and 50 mg/kg, showed significantly sustained plasma profiles compared to i.v. and p.o. administration. Administering 10 and 50 mg/kg of griseofulvin nanocrystals as 10 mL/kg, instead of 2.5 mL/kg, improved Cmax but AUC was unchanged. The present study showed that the bioavailability of griseofulvin, administered as nano- and microparticles, increased significantly after s.c. administration (60-100%) compared with p.o. dosing (17%). The drug is currently orally administered and clearly exposed to a significant first pass metabolism, i.e. an ideal candidate for an alternative administration route, like s.c. injection.

A predictive transport model for convective drying of polymer strip films loaded with a BCS Class II drug.

Drying is an important unit operation in the manufacturing of polymer strip films as it affects various film quality attributes. Optimal design and control of convective drying process require models that capture the impact of critical process parameters such as air temperature and velocity on the temporal evolution of film thickness and moisture. Here, a detailed transport model was presented to capture moisture diffusion, heat transfer and moving boundary in convective drying of polymer strip films loaded with griseofulvin (GF), a poorly water-soluble drug. It incorporates a solvent diffusivity model based on free-volume theory. Experimentally, film precursor suspensions were prepared by mixing silica-coated and micronized GF powder with an aqueous solution of hydroxypropyl methylcellulose (HPMC)-glycerin. Films were cast and moisture-time variation during drying was measured. The transport model, whose diffusivity parameters were estimated using drying data at a reference condition, was validated at different drying conditions and wet film thicknesses. It delineates underlying mechanisms of drying kinetics and demarcates a smooth transition from constant-rate to falling-rate period. Overall, our results suggest that the transport model is capable of predicting the temporal evolution of moisture and final film thickness at different drying air velocities and temperatures with reasonable accuracy.

The impact of cinnarizine and griseofulvin on juvenile and adult stages of Schistosoma mansoni.

Schistosomiasis affects millions globally. There is no vaccine, and treatment depends entirely on praziquantel (PZQ). Field isolates exhibit reduced susceptibility to PZQ, and resistance has been experimentally induced, suggesting that reliance on a single treatment is particularly dangerous. The present study investigated the value of cinnarizine and griseofulvin against Schistosoma mansoni through their in vitro effects on adult worms and oviposition as well as in vivo evaluation in early and late infection, compared to PZQ, in a preliminary experimental model. In vitro, both cinnarizine and griseofulvin showed uncoupling, sluggish worm movement and complete absence of ova at 100 µg/ml. In early infection, cinnarizine showed a significant reduction in the number of porto-mesenteric couples compared to the griseofulvin and control groups, a finding similar to PZQ. Remarkably, cinnarizine significantly exceeded PZQ and griseofulvin in reducing the total worm burden. In late infection, cinnarizine and griseofulvin showed results similar to PZQ by significantly reducing the numbers of hepatic and porto-mesenteric couples and total worm burden compared to controls. Cinnarizine performed better than griseofulvin by reducing hepatic and intestinal ovum counts, and it led to complete disappearance of the first two immature stages. The current work suggests the possibility of using cinnarizine and griseofulvin, mainly in late S. mansoni infection, especially cinnarizine, which showed similar results to PZQ and surpassed it in early infection. Further studies are required to elucidate their exact mechanisms of action and particularly their synergistic effect with PZQ.

Utility of Laboratory Test Result Monitoring in Patients Taking Oral Terbinafine or Griseofulvin for Dermatophyte Infections.

Importance: Terbinafine hydrochloride and griseofulvin are effective oral treatments for dermatophyte infections but have been associated with hepatic and hematologic abnormalities. The prevalence of alanine aminotransferase elevations, aspartate aminotransferase elevations, anemia, lymphopenia, and neutropenia among adults and children taking terbinafine and griseofulvin is unclear. Objective: To measure the rate of laboratory test result abnormalities in healthy adults and children taking terbinafine or griseofulvin for dermatophyte infections. Design, Setting, and Participants: This retrospective study assessed adults and children taking terbinafine or griseofulvin for dermatophyte infections from January 1, 2006, to December 31, 2016. Data were collected from one Midwest health care system. Exclusion criteria were preceding diagnosis of hepatic or hematologic condition and preceding or concurrent use of oral ketoconazole, amphotericin, or itraconazole. Main Outcomes and Measures: The rates of elevated alanine aminotransferase measurements, elevated aspartate aminotransferase measurements, anemia, lymphopenia, and neutropenia in adults and children taking terbinafine, griseofulvin microsize, or griseofulvin ultramicrosize were calculated. Secondary measures included rates of baseline abnormalities, frequency of laboratory test results that required additional testing or discontinued use of medication, and laboratory test result monitoring practices. Results: This study included laboratory data from 4985 patients (mean [SD] age, 42.8 [20.3] years; 2288 [45.9%] female) receiving 4309 courses of terbinafine, 634 courses of griseofulvin microsize, and 159 courses of griseofulvin ultramicrosize. We identified a low rate of laboratory test result abnormalities in patients taking terbinafine or griseofulvin. When laboratory test result abnormalities occurred, most were low grade (212 [93.4%] grade 1) and did not require subsequent laboratory test result evaluation or discontinued use of medication (15 051 [99.9%]). Elevations in alanine aminotransferase measurements were detected infrequently and were comparable to baseline detection rates (61 [3.5%] vs 95 [3.6%] for terbinafine, 2 [2.1%] vs 3 [3.7%] for griseofulvin microsize, and 0 vs 2 [5.0%] for griseofulvin ultramicrosize). Rates of elevated aspartate aminotransferase measurements, anemia, lymphopenia, and neutropenia were also infrequent and comparable to baseline rates. Conclusions and Relevance: In this study. the rates of alanine aminotransferase elevations, aspartate aminotransferase elevations, anemia, lymphopenia, and neutropenia in adults and children taking terbinafine or griseofulvin were low and equivalent to the baseline rates of abnormalities in this population. Routine interval laboratory test result monitoring appears to be unnecessary in adults and children without underlying hepatic or hematologic conditions taking terbinafine or griseofulvin for dermatophyte infections. Abandoning frequent laboratory monitoring can decrease unnecessary health care spending, decrease patient psychological angst associated with blood draws, and allow for expanded use of these effective oral medications.

Tinea capitis in children: a systematic review of management.

BACKGROUND: Tinea capitis is the most common cutaneous fungal infection in children. OBJECTIVES: This review aims to evaluate the differences that exist between medications for the treatment of tinea capitis, to determine whether there are any significant adverse effects associated and to define the usefulness of sample collection methods. METHODS: We conducted a systematic literature search of available papers using the databases PubMed, OVID, Cochrane Libraries and ClinicalTrials.gov. Twenty-one RCTs and 17 CTs were found. RESULTS: Among the different antifungal therapies (oral and combination thereof), continuous itraconazole and terbinafine had the highest mycological cure rates (79% and 81%, respectively), griseofulvin and terbinafine had the highest clinical cure rates (46% and 58%, respectively) and griseofulvin and terbinafine had the highest complete cure rate (72% and 92%, respectively). Griseofulvin more effectively treated Microsporum infections; terbinafine and itraconazole more effectively cured Trichophyton infections. Only 1.0% of children had to discontinue medication based on adverse events. T. tonsurans was the most common organism found in North America, and hairbrush collection method is the most efficient method of sample collection. Additionally, using a hairbrush, toothbrush or cotton swab to identify the infecting organism(s) is the least invasive and most efficient method of tinea capitis sample collection in children. CONCLUSIONS: Current dosing regimens of reported drugs are effective and safe for use in tinea capitis in children.

Melt Extrusion for a High Melting Point Compound with Improved Solubility and Sustained Release.

The objective of the current study was to develop an amorphous solid dispersion for a high melting point compound, griseofulvin (GRF), with an enhanced solubility and a controlled release pattern utilizing hot melt extrusion (HME) technology. Hypromellose acetate succinate (HPMCAS, Shin-Etsu AQOAT®, medium particle size) was explored as the polymeric carrier, while hypromellose (HPMC, Metolose® SR) was chosen as the release rate control agent. GRF presented an HPMCAS grade-dependent solubility: AS-HMP > AS-MMP > AS-LMP. At 10 wt.% loading, the release of GRF was prolonged to 6 h with the incorporation of 10% HPMC 90SH-100SR, while its solubility was enhanced up to sevenfold. Fourier transform infrared spectroscopy (FT-IR) identified the H-bonding between drug and polymers. Element analysis utilizing X-ray photoelectron spectroscopy (XPS) discovered that less GRF aggregated on the surface of binary powders compared with ternary powders containing HPMC, indicating the relatively poor wettability of the latter one. The morphology of extrudates was observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM), illustrating a much smoother and uniform surface of binary extrudates. Immediate release tablets including 10% super-disintegrant L-HPC were able to achieve identical dissolution profile as the powders of extrudates.

Oral antifungal medication for toenail onychomycosis.

BACKGROUND: Fungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely affected, it can interfere with normal daily activities. Treatment is taken orally or applied topically; however, traditionally topical treatments have low success rates due to the nail's physical properties. Oral treatments also appear to have shorter treatment times and better cure rates. Our review will assist those needing to make an evidence-based choice for treatment. OBJECTIVES: To assess the effects of oral antifungal treatments for toenail onychomycosis. SEARCH METHODS: We searched the following databases up to October 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We sought to identify unpublished and ongoing trials by correspondence with authors and by contacting relevant pharmaceutical companies. SELECTION CRITERIA: RCTs comparing oral antifungal treatment to placebo or another oral antifungal treatment in participants with toenail onychomycosis, confirmed by one or more positive cultures, direct microscopy of fungal elements, or histological examination of the nail. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 48 studies involving 10,200 participants. Half the studies took place in more than one centre and were conducted in outpatient dermatology settings. The participants mainly had subungual fungal infection of the toenails. Study duration ranged from 4 months to 2 years.We assessed one study as being at low risk of bias in all domains and 18 studies as being at high risk of bias in at least one domain. The most common high-risk domain was 'blinding of personnel and participants'.We found high-quality evidence that terbinafine is more effective than placebo for achieving clinical cure (risk ratio (RR) 6.00, 95% confidence interval (CI) 3.96 to 9.08, 8 studies, 1006 participants) and mycological cure (RR 4.53, 95% CI 2.47 to 8.33, 8 studies, 1006 participants). Adverse events amongst terbinafine-treated participants included gastrointestinal symptoms, infections, and headache, but there was probably no significant difference in their risk between the groups (RR 1.13, 95% CI 0.87 to 1.47, 4 studies, 399 participants, moderate-quality evidence).There was high-quality evidence that azoles were more effective than placebo for achieving clinical cure (RR 22.18, 95% CI 12.63 to 38.95, 9 studies, 3440 participants) and mycological cure (RR 5.86, 95% CI 3.23 to 10.62, 9 studies, 3440 participants). There were slightly more adverse events in the azole group (the most common being headache, flu-like symptoms, and nausea), but the difference was probably not significant (RR 1.04, 95% CI 0.97 to 1.12; 9 studies, 3441 participants, moderate-quality evidence).Terbinafine and azoles may lower the recurrence rate when compared, individually, to placebo (RR 0.05, 95% CI 0.01 to 0.38, 1 study, 35 participants; RR 0.55, 95% CI 0.29 to 1.07, 1 study, 26 participants, respectively; both low-quality evidence).There is moderate-quality evidence that terbinafine was probably more effective than azoles for achieving clinical cure (RR 0.82, 95% CI 0.72 to 0.95, 15 studies, 2168 participants) and mycological cure (RR 0.77, 95% CI 0.68 to 0.88, 17 studies, 2544 participants). There was probably no difference in the risk of adverse events (RR 1.00, 95% CI 0.86 to 1.17; 9 studies, 1762 participants, moderate-quality evidence) between the two groups, and there may be no difference in recurrence rate (RR 1.11, 95% CI 0.68 to 1.79, 5 studies, 282 participants, low-quality evidence). Common adverse events in both groups included headache, viral infection, and nausea.Moderate-quality evidence shows that azoles and griseofulvin probably had similar efficacy for achieving clinical cure (RR 0.94, 95% CI 0.45 to 1.96, 5 studies, 222 participants) and mycological cure (RR 0.87, 95% CI 0.50 to 1.51, 5 studies, 222 participants). However, the risk of adverse events was probably higher in the griseofulvin group (RR 2.41, 95% CI 1.56 to 3.73, 2 studies, 143 participants, moderate-quality evidence), with the most common being gastrointestinal disturbance and allergic reaction (in griseofulvin-treated participants) along with nausea and vomiting (in azole-treated participants). Very low-quality evidence means we are uncertain about this comparison's impact on recurrence rate (RR 4.00, 0.26 to 61.76, 1 study, 7 participants).There is low-quality evidence that terbinafine may be more effective than griseofulvin in terms of clinical cure (RR 0.32, 95% CI 0.14 to 0.72, 4 studies, 270 participants) and mycological cure (RR 0.64, 95% CI 0.46 to 0.90, 5 studies, 465 participants), and griseofulvin was associated with a higher risk of adverse events, although this was based on low-quality evidence (RR 2.09, 95% CI 1.15 to 3.82, 2 studies, 100 participants). Common adverse events included headache and stomach problems (in griseofulvin-treated participants) as well as taste loss and nausea (in terbinafine-treated participants). No studies addressed recurrence rate for this comparison.No study addressed quality of life. AUTHORS' CONCLUSIONS: We found high-quality evidence that compared to placebo, terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis, with moderate-quality evidence of excess harm. However, terbinafine probably leads to better cure rates than azoles with the same risk of adverse events (moderate-quality evidence).Azole and griseofulvin were shown to probably have a similar effect on cure, but more adverse events appeared to occur with the latter (moderate-quality evidence). Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin (low-quality evidence).Only four comparisons assessed recurrence rate: low-quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo, but there may be no difference between them.Only a limited number of studies reported adverse events, and the severity of the events was not taken into account.Overall, the quality of the evidence varied widely from high to very low depending on the outcome and comparison. The main reasons to downgrade evidence were limitations in study design, such as unclear allocation concealment and randomisation as well as lack of blinding.

Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions.